PMID- 1973754
TI  - [Experience with the Champy plate in the management of fractures of the articular
      process].
AB  - Authors describe their experience with the use of Champy plate, gained in their
      19 cases, in the treatment of the fractures of the articular process. They had
      good results, and find the use of this method more favourable than the
      osteosynthesis with wire ligatures.

PMID- 1973753
TI  - [Correlations between the ABO blood group system and tendon rupture].
AB  - 53 per cent of the 873 cases of subcutaneous (spontaneous) tendon ruptures,
      treated in the National Institute of Traumatology belonged to the blood group O,
      and that was significantly higher than in the healthy population (31.1 per cent)
      of Hungary. The ratio of the tendon rupture patients belonging to the blood group
      A was significantly lower (27.1 per cent) than in the population (42,4 per cent).
      The ratio of the cases belonging to the blood group O among the multiple tendon
      rupture and rerupture patients proved to be over 70 per cent. On the basis of
      their data authors think that there is a relation between the ABO blood group
      system and the tendon rupture: those belonging to the blood group O are more
      endangered by, those belonging to the blood group A are more protected against
      tendon rupture. No relation was found between the Rh(D) blood group system and
      the tendon rupture.

PMID- 1973755
TI  - [Injury of the rotator cuff. I. Morphological and patho-physiological basis].
AB  - Authors summarize the basic features of the functional anatomy and pathogenesis
      of the rotator cuff tears, essential for clinical practice. On the basis of
      literary data and own experiences a new classification of the rotator cuff tears
      was elaborated that can be reliably used in operative indications.

PMID- 1973756
TI  - [Necrolysis in burns using fibrinolysin and deoxyribonuclease].
AB  - Fibrolan was used altogether in 42 cases. This product, containing fibrinolysin
      and sesoxyribonuclease may be used favourably to remove necrotic tissues by
      conservative surgery until the extent of about 15 per cent burned surface. The
      necrolysis in burned injuries of grade II/2 is completed in the majority of the
      cases in 5-10 days, after this the development of the epithelium is finished in 5
      10 days. If operation would be necessary, this can be performed after the end of
      the necrolysis with more favourable prospects. From the viewpoint of the technics
      of application and considering the cost too, the unguent is more favourable. The
      therapy had not to be interrupted because of complication or side effects.

PMID- 1973757
TI  - [Method of fracture fixation using external fixation devices].
AB  - An improvement of the results of treatment can be reached, beside respecting the
      indication of external fixateurs, with correct tactics of the treatment. Because
      of the disadvantages of the fixateur externe, we strive to restrict their use, to
      the time by all means necessary, and if possible to use other methods of
      fixation. This is motivated especially by the effect on fracture healing and the
      hindering of the movements and activity of the patient.

PMID- 1973758
TI  - [Rehabilitation problems in traumatic spinal cord injuries following spinal
      stabilization using Harrington's fixation device].
AB  - Authors describe their experiences in medical rehabilitation of 18 patients with
      traumatic injuries of the medulla after spinal stabilisation with Harrington
      instrument. The Harrington method is a classical method for spinal stabilization
      used in the whole world. Besides its doubtless advantages experiences are
      gathered on its numerous disadvantages: It is not suitable for direct reduction,
      its stability is insufficient against flexion and extension forces, its
      biomechanical characteristics are not the most favourable in respect of
      consolidation, it is too long and includes healthy sections of the spine in
      immobilization, finally external fixation is needed. For all this, the claims of
      modern rehabilitation cannot be fulfilled. In possession of newer, more modern
      methods (fixateur interne, groove plate) the use of it is not at all recommended.

PMID- 1973759
TI  - [Manus cornuta in ancient and medieval works of art].

PMID- 1973760
TI  - [Open fracture-dislocation of the ankle].

PMID- 1973761
TI  - [Post-traumatic avascular necrosis of the tubereculum majus].
AB  - Posttraumatic avascular bone necrosis occurs rarely on the major tubercle. In the
      early stage it may cause diagnostical problem at the evaluation of the
      Roentgenogram. It can be confused with a tumor, metastasis and tuberculosis.
      Later it shows a characteristic picture and causes rarely diagnostic
      difficulties. Authors describe a case of their own and discuss briefly the
      supposed causes of the disease, the possibilities of early recognition and
      treatment.

PMID- 1973762
TI  - [Isolated neuropraxy of the musculocutaneous nerve].
AB  - Authors describe a case of isolated posttraumatic neuropraxy of the
      musculocutaneous nerve. With the presentation of this very rare case attention is
      called, based on literary date, to the fact that the above injury can be mixed
      with the distal tendon rupture of the biceps.

PMID- 1973763
TI  - [A case of hibernoma of unusual localization].

PMID- 1973764
TI  - [Orthofix, a dynamic axial fixator].

PMID- 1973765
TI  - [Special indications for Helal's serial metatarsal osteotomy].
AB  - Authors discuss, presenting case reports, the operative indications of Helal's
      metatarsal serial osteotomy. In their first case this kind of operation was
      performed because of metatarsalgia, following traumatic amputation of the hallux.
      In their second case, in a young female with rheumatoid arthritis, considering
      the age of the patient and the destruction in the metatarsophalangeal joints too,
      Helal's metatarsus osteotomies were completed with the resection of the basis of
      the ground phalanx. In both cases good correction was reached and without any
      complaints.

PMID- 1973766
TI  - [Critical analysis of osteosynthesis of fractures of the femoral diaphysis].
AB  - Authors analyse the osteosyntheses of 98,417 segmental fractures of the femoral
      diaphysis. Beside the 72 per cent of excellent and good results in 19 per cent
      complications were found, especially after using plate osteosynthesis. In spite
      of the fact that Kuentscher nailing seems to be the method of choice in this
      paper the problem is not analysed from the viewpoint of indication but from that
      of the causes of prolonged healing. On the basis of their own experiences they
      call attention to the danger of complications. They think the choice of the most
      suitable method of treatment of very great importance and also the regular
      control, the aftertreatment and readiness to cooperation of the patients.

PMID- 1973767
TI  - [Management of hallux varus].
AB  - Authors describe the congenital and acquired forms of the rarely occurring hallux
      varus on the basis of the material of 14 patients, treated in 1951-87 on the
      Orthopaedic Department of the Semmelweis University Budapest. In 11 cases the
      deformity was congenital and in the majority bilateral, multiple, together with
      other foot deformities.

PMID- 1973768
TI  - Comparison of placebo with L-thyroxine alone or with carbimazole for treatment of
      sporadic non-toxic goitre.
AB  - The efficacy of treatment with TSH-suppressive doses of L-thyroxine (T4, 2.5
      micrograms/kg body weight daily) either alone or combined with carbimazole (CBZ,
      40 mg daily) was studied in 78 patients with sporadic non-toxic goitre in a
      prospective placebo-controlled double-blind randomised clinical trial. Treatment
      was given for 9 months, with 9 months of follow-up. A response to treatment as
      measured by ultrasonography was found in 58% of the T4 group, in 35% of the
      T4/CBZ group, and in 5% of the placebo group. The mean (SEM) decrease of thyroid
      volume at 9 months in the responders was 25% (2). After discontinuation of
      treatment, thyroid volume increased in the responders and had returned to base
      line values after 9 months of follow-up. In the placebo group mean thyroid volume
      had increased by 6% (4) at 4 months, 20% (7) at 9 months, and 27% (8) at 18
      months. The findings show that untreated sporadic non-toxic goitre continues to
      increase in size; T4 is effective in the treatment of the disorder; and the
      addition of CBZ has no therapeutic advantage.

PMID- 1973769
TI  - Isolation of fetal trophoblast cells from peripheral blood of pregnant women.
AB  - Fetal trophoblast cells were isolated from maternal peripheral blood by means of
      murine monoclonal antibodies of high specificity and affinity for human
      syncytiotrophoblast and nonvillous cytotrophoblast cells. The cells were isolated
      in sufficient numbers to allow polymerase chain reaction (PCR) amplification of
      the Y-chromosome-specific DNA sequence from the peripheral blood of thirteen
      pregnant women. The fetal sex predicted by PCR analysis of the isolated
      trophoblast cells accorded with that ascertained by karyotyping of chorionic
      villus samples in eleven of twelve women studied in early pregnancy and with the
      sex of the baby on delivery in one woman studied at 34 weeks' gestation.
      Isolation of these fetal cells could allow noninvasive diagnosis of a wide range
      of inherited disorders.

PMID- 1973770
TI  - Reduction in pneumonia mortality and total childhood mortality by means of
      community-based intervention trial in Gadchiroli, India.
AB  - In a community-based intervention trial to reduce childhood mortality from
      pneumonia the intervention area included 58 villages (6176 children aged 0-4
      years) and the control area 44 villages (3947 children) in Gadchiroli, India. The
      interventions included mass education about childhood pneumonia and case
      management of pneumonia by paramedics, village health workers, and traditional
      birth attendants (TBAs) who were trained to recognise childhood pneumonia and
      treat it with co-trimoxazole. Parents sought treatment, and coverage was 76%
      without active case-detection efforts. The case-fatality rate among the 612 cases
      treated by health workers was 0.8%, compared with 13.5% in the control area.
      After a year of intervention pneumonia-specific childhood mortality was
      significantly lower in the intervention than in the control area (8.1 vs 17.5
      deaths per 1000 children under 5 years); the difference between the areas was
      greatest in children under 1 year. The differences in infant mortality (89 vs 121
      per 1000) and total under-5 mortality (28.5 vs 40.7 per 1000) were highly
      significant. Mortality from other causes remained similar in the two areas but
      neonatal mortality due to birth injury and prematurity was significantly lower in
      the intervention area, presumably owing to the combination of better maternal and
      neonatal care by the TBAs trained in the project and the availability of
      treatment for pneumonia. The cost of co-trimoxazole was US $0.025 per child per
      year ($2.64 per child saved).

PMID- 1973771
TI  - Importance of chronic aspiration in recipients of heart-lung transplants.
AB  - In a series of eleven recipients of heart-lung transplants (HLT), five have
      obliterative bronchiolitis. Five of the eleven patients have chronic cough as
      well as slower than normal gastric emptying and/or oesophageal dysmotility; all
      five have evidence of bronchiectasis and three have obliterative bronchiolitis.
      Three of the patients improved after the introduction of treatment to prevent
      reflux, and another, who had a large phytobezoar, improved after pyloroplasty. In
      patients with chronic cough after HLT, with or without dyspeptic symptoms or
      recurring pulmonary sepsis, investigation of oesophageal motility and gastric
      emptying should be undertaken.

PMID- 1973772
TI  - Evidence for intrafamilial transmission of hepatitis B virus from sequence
      analysis of mutant HBV DNAs in two Chinese families.
AB  - To study the heterogeneity of hepatitis B virus (HBV) DNAs in Hong Kong, where
      HBV infection is endemic, serum specimens from 90 HBsAg carrier children were
      systematically tested with nine oligonucleotide probes representing conserved
      sequences in the viral genome. In a pair of twins and their cousin (belonging to
      family H) and an unrelated child (family Y) serum HBV DNA annealed to all but one
      probe, a sequence located between the core and pre-S regions of the viral genome
      (positions 2723-2738; EcoRI site 1). Serum from the H twins' aunt and the father
      and paternal grandparents in the Y family were also HBV DNA-positive. The
      nucleotide sequences in positions 2701-2800 were analysed. The same point
      mutation, C to T in position 2735, was present in the HBV DNAs from 7 individuals
      in the two families. All 4 H family members had the same HBV DNA sequence. The
      HBV DNA sequences found in the Y daughter, father, and grandfather were identical
      and they were different from the H family mutant. These results provided evidence
      at the DNA level of intrafamilial transmission within these Chinese families.

PMID- 1973773
TI  - Shuck your oysters with care.

PMID- 1973774
TI  - Ever so risky.

PMID- 1973775
TI  - A suitable case for intimacy.

PMID- 1973776
TI  - Toxic epidermal necrolysis--a premature requiem?

PMID- 1973777
TI  - Na(+)-Ca2+ exchanger and cardiac contraction.

PMID- 1973778
TI  - Chiropracters and low back pain.

PMID- 1973779
TI  - Current and future dimensions of the HIV/AIDS pandemic in women and children.
AB  - The WHO estimates that during the first decade of the HIV/AIDS pandemic there
      were about 500,000 cases of AIDS in women and children, most of which have been
      unrecognised. During the 1990s, WHO estimates that the pandemic will kill an
      additional 3 million or more women and children world wide. HIV infection among
      heterosexual populations has been increasing throughout the world during the
      1980s. AIDS has become the leading cause of death for women aged 20-40 in major
      cities in the Americas, Western Europe, and sub-Saharan Africa. In these cities,
      infant and child mortality could be as much as 30% greater than what would
      otherwise have been expected. During the 1990s, not only can hundreds of
      thousands of paediatric AIDS cases be expected, but also more than a million
      uninfected children will be orphaned because their HIV-infected mothers and
      fathers will have died from AIDS.

PMID- 1973780
TI  - Genetic variation in response to 6-mercaptopurine for childhood acute
      lymphoblastic leukaemia.
AB  - 6-mercaptopurine (6-MP) can be inactivated by S-methylation, which is catalysed
      by thiopurine methyltransferase (TPMT). An alternative metabolic route leads to
      the formation of cytotoxic 6-thioguanine nucleotides (6-TGN). To investigate
      whether these two pathways compete with each other to affect the therapeutic
      response to 6-MP, 6-TGN concentrations and TPMT enzymatic activity were measured
      in erythrocytes (RBC) from 95 children on long-term 6-MP therapy for
      lymphoblastic leukaemia (ALL). RBC TPMT activities were also measured in 130
      control children and 104 long-term survivors of ALL no longer on treatment. The
      95 children on 6-MP showed wide interindividual differences in RBC 6-TGN
      concentrations at the full protocol dose of 75 mg/m2, and RBC 6-TGN
      concentrations correlated negatively with RBC TPMT activity. Children with 6-TGN
      concentrations below the group median had higher TPMT activities and a higher
      subsequent relapse rate. 50 of the 104 long-term survivors had been treated with
      "gentle" low-dose protocols, and this subgroup contained an excess of children
      with lower TPMT activities compared with normal controls. These results indicate
      that genetically determined TPMT activity may be a substantial regulator of the
      cytotoxic effect of 6-MP, an effect which in turn could be important in
      influencing the outcome of therapy for childhood ALL.

PMID- 1973781
TI  - Colposcopic diagnosis and treatment of cervical dysplasia at a single clinic
      visit. Experience of low-voltage diathermy loop in 1000 patients.
AB  - In a study of 1000 women referred over 20 months with abnormal smears and in whom
      the entire transformation zone could be seen the aim was to test the feasibility
      of colposcopic assessment and treatment at one visit to the clinic. 897 women
      needed only one visit. This was achieved by using a modification of the large
      loop diathermy excision technique and by careful attention to the timing of the
      clinic visit. 103 required further visits, for the following reasons: incomplete
      excision on histology and/or subsequently abnormal smear (85), secondary
      haemorrhage (6), microinvasion or invasive carcinoma (9), biopsy specimens
      unusable (3). Further treatment was given in 4.1% of the cervical dysplasias. All
      patients treated in a single visit preferred this approach to the alternative of
      colposcopic assessment and biopsy followed, after histological examination, by
      local ablation by laser, excision by loop biopsy technique, or cone biopsy.

PMID- 1973782
TI  - Anatomy, physiology, and pathology of epilepsy.

PMID- 1973783
TI  - Haemophilic AIDS patient loses claim in Australia.

PMID- 1973784
TI  - Bone density screening for osteoporosis.

PMID- 1973785
TI  - Fluoride and vertebral fractures.

PMID- 1973787
TI  - Anti-HCV positive patients in dialysis units?

PMID- 1973786
TI  - Ovarian relaxin is not essential for dilatation of cervix.

PMID- 1973788
TI  - Early US experience with anti-HCV kit in blood donors.

PMID- 1973790
TI  - Percutaneous coronary angioplasty with mid-infrared laser and a new multifibre
      catheter.

PMID- 1973789
TI  - Suppression of hepatitis C virus RNA by interferon-alpha.

PMID- 1973791
TI  - Indomethacin in severe head injury.

PMID- 1973792
TI  - Mycoplasma-like organisms.

PMID- 1973793
TI  - Isolation of "Mycoplasma incognitus".

PMID- 1973794
TI  - Mycoplasma and AIDS.

PMID- 1973795
TI  - Intrathecal zidovudine for AIDS dementia.

PMID- 1973796
TI  - Risk of non-Hodgkin lymphoma and Kaposi's sarcoma in homosexual men.

PMID- 1973797
TI  - Indirect memory for words presented during anaesthesia.

PMID- 1973798
TI  - LCAT activity as a prognostic liver function test.

PMID- 1973799
TI  - Endoscopic correction of primary vesicoureteric reflux.

PMID- 1973800
TI  - Non-coronary thrombolysis.

PMID- 1973801
TI  - Apolipoprotein (a) and ischaemic heart disease.

PMID- 1973802
TI  - Reconstitution of interleukin-2 with albumin for infusion.

PMID- 1973803
TI  - Multiresistant Salmonella typhi in India.

PMID- 1973804
TI  - Toxic reaction following treatment of typhoid fever with pefloxacin.

PMID- 1973805
TI  - Transferable cephalosporin resistance not inhibited by clavulanate in Escherichia
      coli.

PMID- 1973806
TI  - Cyclophosphamide versus ifosfamide in paediatric oncology.

PMID- 1973807
TI  - Relation between serum cholesterol and diabetic nephropathy.

PMID- 1973808
TI  - Potential problems with random zero sphygmomanometer.

PMID- 1973809
TI  - Erythropoietin, aluminium, and anaemia in patients on haemodialysis.

PMID- 1973810
TI  - Cushing's syndrome and medroxyprogesterone acetate.

PMID- 1973811
TI  - Vaginal ultrasound and endometrial carcinoma.

PMID- 1973812
TI  - Total genomic DNA probe to detect Giardia lamblia.

PMID- 1973813
TI  - Normal development after exposure to mifepristone in early pregnancy.

PMID- 1973814
TI  - Reduction of lymphorrhagia from ruptured thoracic duct by somatostatin.

PMID- 1973815
TI  - Comparison of immunoscintigraphy and colloid scintigraphy of bone marrow.

PMID- 1973816
TI  - Provision of help after major disasters.

PMID- 1973817
TI  - Cardiac rupture and fibrinolytic therapy.

PMID- 1973818
TI  - Non-spastic paraparesis associated with HTLV-I.

PMID- 1973819
TI  - Prevention of pressure sores.

PMID- 1973820
TI  - Effect of albumin on acyl-CoA: lysolecithin acyltransferase, lysolecithin:
      lysolecithin acyltransferase and acyl-CoA hydrolase from rabbit lung.
AB  - Acyl-CoA: lysolecithin and lysolecithin: lysolecithin acyltransferases, as well
      as acyl-CoA hydrolase are important enzymes in lung lipid metabolism. They use
      amphiphylic lipids as substrates and differ in subcellular localization. In this
      sense, lipid-protein interactions can be an essential factor in their activity.
      We have studied the effect of albumin, as lipid-binding protein model, in the
      activities of these enzymes. Acyl-CoA hydrolase was inhibited in the presence of
      albumin, whereas acyl-CoA: lysolecithin acyltransferase showed a complex effect
      of activation depending on both albumin concentration and palmitoyl
      CoA/lysolecithin molar ratio. Lysolecithin: lysolecithin acyltransferase was
      affected differentially on its two activities. Hydrolysis remained unaffected and
      transacylation was inhibited by albumin. These results are consequence of the
      interaction of albumin with both lipidic substrates that changes their critical
      micellar concentration.

PMID- 1973821
TI  - Molecular changes in UV-induced and gamma-ray-induced mutations in human
      lymphoblastoid cells.
AB  - We have characterized the structural changes in the hypoxanthine-guanine
      phosphoribosyltransferase (HPRT) gene of 14 UV-induced, 15 gamma-ray-induced and
      17 spontaneous mutants of human lymphoblastoid cells selected for 6-thioguanine
      (6TG) resistance. Southern blot analysis using the full-length HPRT cDNA as a
      probe revealed that 29% (5/17) of the spontaneous mutants contained detectable
      alterations in their restriction fragment patterns. Among the 15 mutants induced
      by gamma rays, 7 (47%) had such alterations indicative of large deletions in the
      HPRT gene. In contrast, all 14 UV-induced mutants exhibited hybridization
      patterns indistinguishable from those of the wild-type cells. These results
      suggest that UV is likely to induce point mutations at the HPRT locus on the
      human chromosome and that the molecular mechanism of UV-induced mutation is quite
      different from that of ionizing radiation-induced mutation or spontaneous
      mutation in human cells.

PMID- 1973822
TI  - Recovery from autoimmunity of MRL/lpr mice after infection with an interleukin
      2/vaccinia recombinant virus.
AB  - Interleukin-2 (IL-2) is a T-cell derived molecule implicated in the clonal
      expansion of antigen-activated T cells and in T-cell development. IL-2 is also
      implicated in autoimmune disease, although its role is still controversial.
      Murine systemic lupus erythematosus (SLE) is a good model for human SLE as most
      of the immunological abnormalities in the human disease also seem to be operative
      in the mouse. Among SLE mice, the MRL/lpr strain develops early in life
      autoimmune diseases such as immune complex-mediated glomerulonephritis, arthritis
      and arteritis. Lymphoid abnormalities associated with those diseases in this
      strain are thymic atrophy and abnormal proliferation of CD3+ CD4- CD8- 'double
      negative' T cells, resulting in massive generalized lymph node enlargement. We
      have therefore now examined the effects of IL-2 on the disease progression in
      MRL/lpr mice using live vaccinia recombinant viruses expressing the human IL-2
      gene. Vaccinated mice showed prolonged survival, decreased autoantibody and
      rheumatoid factor titres, marked attenuation of kidney interstitial infiltration
      and intraglomerular proliferation, as well as clearance of synovial mononuclear
      infiltrates. Inoculation with the IL-2/vaccinia recombinant virus led, in
      addition, to drastic reduction of the double-negative T-cell population, improved
      thymic differentiation and restoration of normal values of mature cells in
      peripheral lymphoid organs.

PMID- 1973823
TI  - Additional deletion in sex-determining region of human Y chromosome resolves
      paradox of X,t(Y;22) female.
AB  - Whether a human embryo develops as a male or a female is determined by the
      presence of the Y chromosome. The sex-determining function lies entirely in
      interval 1A, inasmuch as most XX individuals with descended testes and normal
      male external genitalia carry this small region of the Y chromosome. We have
      localized an essential part of the sex-determining function to a portion of
      interval 1A, on the basis of the discovery of a female with a reciprocal Y;22
      translocation and part of 1A deleted at the translocation breakpoint. Recently, a
      paradox has arisen with the report of four partially masculinized XX individuals
      who carry only a portion of interval 1A--a portion that does not overlap the
      deletion in the X,t(Y;22) female. These recent findings imply that the sex
      determining function lies in the portion of 1A present in the four XX intersexes
      and not in the portion deleted in the X,t(Y;22) female. To explain the X,t(Y;22)
      individual, it was proposed that she was female because of a chromosomal position
      effect or delayed development of the gonadal soma. Here we report that the
      X,t(Y;22) female has a deletion of a second portion of interval 1A--a portion
      corresponding closely to that present in the XX intersexes. This resolves the
      apparent contradiction. Nonetheless, phenotype-genotype correlations suggest that
      two or more genetic elements in interval 1A may contribute to the sex-determining
      function of the Y chromosome. The X,t(Y;22) female lacks the ZFY gene but does
      not exhibit the complex phenotype known as Turner's syndrome, arguing against the
      hypothesis that ZFY is the Turner's syndrome gene on the Y chromosome.

PMID- 1973824
TI  - Structural model of ATP-binding proteins associated with cystic fibrosis,
      multidrug resistance and bacterial transport.
AB  - The ATP-binding cassette (ABC) superfamily of transport systems now includes over
      thirty proteins that share extensive sequence similarity and domain organization.
      This superfamily includes the well characterized periplasmic binding protein
      dependent uptake systems of prokaryotes, bacterial exporters, and eukaryotic
      proteins including the P-glycoprotein associated with multidrug resistance in
      tumours (MDR), the STE6 gene product that mediates export of yeast a-factor
      mating pheromone, pfMDR that is implicated in chloroquine resistance of the
      malarial parasite, and the product of the cystic fibrosis gene (CFTR). Here we
      present a tertiary structure model of the ATP-binding cassettes characteristic of
      this class of transport system, based on similarities between the predicted
      secondary structures of members of this family and the previously determined
      structure of adenylate kinase. This model has implications for both the molecular
      basis of transport and cystic fibrosis and provides a framework for further
      experimentation.

PMID- 1973825
TI  - [Intervention with beta-blockers in acute myocardial infarct].

PMID- 1973826
TI  - Inappropriate use of inhaled beta agonists in asthma.

PMID- 1973827
TI  - Inhibition of c-erbB-2 oncogene expression by estrogens in human breast cancer
      cells.
AB  - The c-erbB-2 oncogene is thought to play a relevant role in the development and
      progression of mammary neoplasia. Using the human breast cancer cell lines T47D
      and MCF7, we found that the arrest of cell growth induced by a steroid-depleted
      medium was accompanied by a strong increase of c-erbB-2 mRNA and of the c-erbB-2
      encoded p185 protein. The treatment of arrested cells with estrogens was found to
      resume cell proliferation and to inhibit dramatically c-erbB-2 expression at both
      mRNA and protein level. The regulation of c-erbB-2 expression was remarkably
      different from that observed for c-myc, which was strongly stimulated by
      estrogens, and ras, whose expression was unaffected all through the treatments.
      In addition, in the normal rat mammary gland undergoing development and
      differentiation during pregnancy and lactation, p185 expression was detected only
      in the functionally differentiated tissue. Altogether, our data indicate that the
      expression of c-erbB-2 is repressed during estrogen-induced proliferation and
      enhanced during growth arrest and/or differentiation of mammary cells.

PMID- 1973828
TI  - A new RFLP in intron 1 of the human c-Ha-ras1 gene and its close relationship
      with the variable tandem repeats in the region 3' to the gene.
AB  - Based on restriction fragment length polymorphism (RFLP) analysis of BamHI or
      MspI fragments, the human c-Ha-ras1 alleles could be divided into two major
      groups, one having about 80 copies of a 28 base pair (bp) sequence in the
      variable tandem repeat (VTR) region 1.4-kilobase pairs (kb) downstream from the
      end of the coding exon and the other having 40 copies of the sequence. We found a
      second RFLP in intron 1 of the c-Ha-ras1 gene at a position about 80 bp upstream
      from the 5'-end of exon 1. The size of the PstI fragments carrying this region is
      either 371 or 359 bp depending on the numbers of a hexanucleotide sequence,
      GGGCCT. In larger fragments, the unit sequence was repeated four times, while in
      smaller fragments it was repeated twice. Unexpectedly, we found that the alleles
      with 80 copies of the 28 bp sequence in the VTR region all carried two repeats of
      GGGCCT in intron 1, while alleles with 40 copies all had four repeats of the
      GGGCCT sequence.

PMID- 1973829
TI  - An oncogenic chromosome 8-9 gene fusion isolated following transfection of human
      ovarian carcinoma cell line DNA.
AB  - Transfection of NIH3T3 cells with genomic DNA from the human ovarian
      adenocarcinoma tumor cell line OVCAR-3 identified ovc, a rearranged human DNA
      sequence which was generated during transfection and which induced both
      morphological transformation and tumorigenesis. A human alu repeat positive 10.5
      kb EcoRI fragment present in all transformants was cloned, and two alu-free
      fragments of 1.8 kb and 2.2 kb were subcloned. The cloned 10.5 kb fragment is not
      biologically active in DNA transfection assays. Probe from the 2.2 kb fragment
      hybridizes to poly A + RNA from the transformants and several human tumor cell
      lines, including OVCAR-3. The 2.2 kb fragment maps to a site on human chromosome
      9 (9p24) not known to contain oncogenic sequences, and identifies a two allele
      polymorphic restriction site. The 1.8 kb fragment maps to human chromosome 8. The
      ovc transforming sequences fail to hybridize to probes to any of 14 known
      oncogenes, indicating that they may represent a previously unknown human
      transforming gene.

PMID- 1973830
TI  - Expression of the HER-2/neu proto-oncogene in normal human adult and fetal
      tissues.
AB  - The HER-2/neu proto-oncogene is homologous with, but distinct from, the epidermal
      growth factor receptor. Current evidence indicates that this gene is frequently
      amplified and/or overexpressed in some human breast and ovarian cancers and that
      these alterations may be clinically important; however, little is known about the
      expression pattern of the gene in normal tissues. Using immunohistochemistry and
      northern blot analyses to identify the HER-2/neu protein and transcript
      respectively, we have evaluated a variety of normal adult and fetal tissues for
      HER-2/neu expression. HER-2/neu protein was identified on cell membranes of
      epithelial cells in the gastro-intestinal, respiratory, reproductive, and urinary
      tract as well as in the skin, breast and placenta. Northern hybridization
      confirmed the presence of the 4.5 kb transcript encoding the protein in these
      tissues. The amount of HER-2/neu message and protein was generally higher in
      fetal tissues than in the corresponding normal adult tissues. HER-2/neu
      expression levels in these normal tissues were similar to the levels found in non
      amplified, non-overexpressing breast cancers and breast cancer cell lines.
      Southern hybridization of extracted DNA showed that none of the normal tissues
      expressing HER-2/neu had amplification of the gene. These results confirm that
      HER-2/neu is normally a membrane constituent of a variety of epithelial cell
      types.

PMID- 1973831
TI  - [Study of the etiologic factors of bucco-dental pathology in handicapped children
      and adolescents].
AB  - Periodontal diseases and dental caries are extremely frequent in children and
      adolescents with sensori-motor handicaps. This study was undertaken to identify
      etiological factors of these affections in order to define preventive measures.
      During a 3-year-period, a survey was performed among 994 handicapped children and
      adolescents from 14 institutional centres of the Rhone-Alpes Region. Factors
      appearing significantly involved in the etiology of periodontal diseases and
      dental caries among this population were insufficient brushing, lack of
      motivation towards oral hygiene of the institution, is staff the severity of the
      motor handicap, and long-term treatments with psychopharmaceutical agents. The
      authors suggest that preventive measures should be taken in order to eliminate
      these disabling dental diseases in handicapped children, mainly a reduction in
      sugar intake, a motivation of the staff to enforce oral hygiene and a limitation
      of psychopharmoceutical treatments.

PMID- 1973832
TI  - The human interleukin-2 receptor beta-chain gene: genomic organization, promoter
      analysis and chromosomal assignment.
AB  - The chromosomal gene for the human interleukin-2 receptor beta-chain (IL-2R beta)
      was isolated and characterized. The entire IL-2R beta gene is composed of ten
      exons spanning about 24.3 kilobases, in which the protein is encoded by the exons
      2-10. The cysteine rich extracellular region which displays a significant
      evolutionary resemblance to other cytokine receptors, as well as growth hormone
      and prolactin receptors, is encoded primarily by exons 3 and 4, whereas the
      membrane proximal, cysteine poor domain showing a homology with type III modules
      of fibronectin is encoded by exon 7. Sequence analysis of the 5'-flanking region
      revealed the presence of potential binding sites for transcription factors such
      as Octamer binding factors, AP-1, AP-2 as well as the 'GC-clusters'. At least
      five potential cap sites were identified by S1 mapping analysis. The 850 bp DNA
      sequence of the 5'-flanking region exhibited constitutive promoter activity when
      it was linked upstream of the HSV-tk reporter gene and then transfected into YT
      cells, a human leukemic cell line. By applying the RFLP linkage analysis, the IL
      2R beta gene has been assigned to chromosome 22q12-13.

PMID- 1973833
TI  - Promoter variation in the ribosomal RNA genes in Drosophila melanogaster strains.
AB  - The sequences of thirty D. melanogaster ribosomal DNA promoter regions have been
      determined. Fifteen of these were isolated from a wild population recently
      captured in North Wootten, England. The other fifteen were isolated from an
      inbred laboratory strain. The overall level of variation is almost twice as high
      in the North Wootten strain as in the inbred laboratory strain. Two mutations at
      nucleotides -17 and -21 relative to transcription start, fall directly within a
      region known to be transcriptionally important. The sequences are also compared
      to eight previously published sequences from another D. melanogaster strain,
      Oregon R. Two of these eight clones have a -17 mutation identical to the one
      found in this study, suggesting that this polymorphism is widespread. Strikingly,
      all eight of these clones carry two single base pair changes not found in any of
      the other thirty clones, indicating the extent with which promoter variants can
      be homogenized and fixed in a population. Polymorphisms show different levels of
      homogenization within the rDNA unit spacer repeats or between different arrays
      depending on the location of the polymorphism. This has implications for the
      evolution of the observed species-specific transcription of ribosomal RNA genes.

PMID- 1973835
TI  - Isolation and analysis of chick homeobox cDNA clones.

PMID- 1973834
TI  - Isolation and characterization of the human tyrosine aminotransferase gene.
AB  - Structure and sequence of the human gene for tyrosine aminotransferase (TAT) was
      determined by analysis of cDNA and genomic clones. The gene extends over 10.9 kbl
      and consists of 12 exons giving rise to a 2,754 nucleotide long mRNA (excluding
      the poly(A)tail). The human TAT gene is predicted to code for a 454 amino acid
      protein of molecular weight 50,399 dalton. The overall sequence identity within
      the coding region of the human and the previously characterized rat TAT genes is
      87% at the nucleotide and 92% at the protein level. A minor human TAT mRNA
      results from the use of an alternative polyadenylation signal in the 3' exon
      which is present but not used at the corresponding position in the rat TAT gene.
      The non-coding region of the 3' exon contains a complete Alu element which is
      absent in the rat TAT gene but present in apes and old world monkeys. Two
      functional glucocorticoid response elements (GREs) reside 2.5 kb upstream of the
      rat TAT gene. The DNA sequence of the corresponding region of the human TAT gene
      shows the distal GRE mutated and the proximal GRE replaced by Alu elements.

PMID- 1973836
TI  - Dinucleotide repeat polymorphisms at the D16S260, D16S261, D16S265, D16S266, and
      D16S267 loci.

PMID- 1973837
TI  - Dinucleotide repeat polymorphisms at the D5S107, D5S108, D5S111, D5S117 and
      D5S118 loci.

PMID- 1973839
TI  - Dinucleotide repeat polymorphisms at the DXS453, DXS454 and DXS458 loci.

PMID- 1973838
TI  - Dinucleotide repeat polymorphisms at the D11S419 and CD3D loci.

PMID- 1973840
TI  - Dinucleotide repeat polymorphisms at the D8S85, D8S87, and D8S88 loci.

PMID- 1973841
TI  - Dinucleotide repeat polymorphisms at the D7S435 and D7S440 loci.

PMID- 1973842
TI  - Diagnosis and treatment of compartment syndrome of the foot.

PMID- 1973843
TI  - Amisulpride versus haloperidol in treatment of schizophrenic patients--results of
      a double-blind study.
AB  - In a double-blind study, 41 schizophrenic patients (ICD, 9th rev.) were divided
      into two groups. With a flexible dose, twenty patients were treated with
      haloperidol, twenty-one with amisulpride. With respect to relevant criteria such
      as age, sex, length and degree of illness, the two groups were comparable. The
      study was conducted over 42 days. As early as within the first 14 days, both
      groups showed significant improvement with respect to their psychotic symptoms.
      When the two groups were compared on the basis of the BPRS subscore for the
      anxiety-depression syndrome, and the AMDP system subscores for the somatic
      depressive syndrome and the hypochondriac syndrome, the amisulpride group showed
      significantly better results than the haloperidol group. The ratings on the EPS
      scales of Webster and Simpson revealed significantly fewer extrapyramidal side
      effects in the amisulpride group. Psychotic symptoms were improved after both
      types of treatment. Amisulpride treatment showed better results with regard to
      depressive symptoms, and less tendency to generate extrapyramidal side-effects.

PMID- 1973845
TI  - [Function of animal peroxisomes--metabolism of purines, amino acids and
      glyoxylate].

PMID- 1973844
TI  - Comparison of the antimanic efficacy of carbamazepine and lithium carbonate by
      double-blind controlled study.
AB  - A multi-institutional study comparing the antimanic effect of carbamazepine (CBZ)
      and lithium carbonate (Li) was performed using a double-blind group comparison
      design in a series of 105 patients with bipolar disorders. CBZ and Li were given
      for four weeks using a fixed-flexible method at an equipotent dose ratio of 1:1,
      starting from an initial dosage of 400 mg with a maximum dosage of 1200 mg. The
      final global improvement rate, based on the number of cases showing moderate to
      marked amelioration of manic symptoms, was 62% in the CBZ group and 59% in the Li
      group, with no significant difference being found between the two groups.
      Incidence of cutaneous side-effects was significantly higher in the CBZ group.
      The mean daily dosage and serum level of CBZ in the fourth week were 674 +/- 239
      mg and 7.3 +/- 2.4 micrograms/ml respectively; these were within the therapeutic
      range. The daily dose and serum level of Li, however, were 710 +/- 239 mg and
      0.46 +/- 0.22 mEq/l, and the Li level seemed to be too low to compare its
      therapeutic effect with that of CBZ. Prior to the present study, approximately
      80% of the patients in both groups had been receiving antipsychotic medication,
      equivalent to 8.0 mg of haloperidol on average, without favorable response. This
      medication was maintained unchanged during treatment. While the shortcomings of
      the present study limit the interpretation of the data, it may be suggested that
      the usefulness of CBZ as a drug for the treatment of manic states is comparable
      to that of Li.

PMID- 1973846
TI  - Homeobox genes and the vertebrate body plan.

PMID- 1973847
TI  - [Systemic thrombolytic therapy of myocardial infarct using streptokinase combined
      with nitroglycerin and beta blockers].

PMID- 1973848
TI  - [Hormonal mechanisms and principles of treatment in dumping syndrome].

PMID- 1973849
TI  - Species differences in carcinogenicity: the role of metabolism in human risk
      evaluation.
AB  - The assessment of human risk from exposure to chemicals is frequently confounded
      by differences in response to those chemicals in laboratory animals. In many
      cases, the basis of the species differences is differences in metabolism and
      pharmacokinetics. Since metabolic and pharmacokinetic data are readily accessible
      in both laboratory animals and humans, risk assessments can be significantly
      improved if these data are incorporated into the process. Several chlorinated
      solvents, perchloroethylene, trichloroethylene, and methylene chloride, have been
      investigated, and the species differences in carcinogenicity have been shown to
      be the result of pharmacokinetic differences between the species. The rates of
      metabolism of these chemicals have been measured in rats and mice in vivo, and
      the species differences observed have been reproduced in vitro using tissue
      fractions and hepatocytes. Identical experiments have been carried out using
      human tissues. The results of these studies together with species-specific
      physiological parameters have been used in a mathematical model to predict human
      cancer risk over a wide range of exposures. This approach provides both an
      explanation for the species differences in response to these chemicals and also a
      more rational approach to human risk assessment.

PMID- 1973850
TI  - Molecular analysis of reactive oxygen-species-induced mammalian gene mutation.
AB  - We have studied the mutagenicity and toxicity of physical and chemical agents in
      the Chinese hamster ovary (CHO) cell line K1-BH4 and its transformant, AS52. The
      AS52 cells lack the normal X-linked mammalian hypoxanthine-guanine
      phosphoribosyltransferase (hprt) gene but instead contain a single autosomally
      integrated copy of the bacterial equivalent, the xanthine-guanine
      phosphoribosyltransferase (gpt) gene. We found that X-rays and neutrons appear to
      be equitoxic to both cell types; however, these physical agents are approximately
      10 times more mutagenic to the gpt gene of AS52 cells than to the hprt gene of K1
      BH4 cells. We reasoned that if reactive oxygens were to mediate the mutagenic
      effects of both radiomimetic chemicals and radiation, then reactive oxygen
      producing chemicals, such as streptonigrin and bleomycin, and oxidizing agents
      such as potassium superoxide and hydrogen peroxide, would exhibit similar levels
      of toxicity but different frequencies of mutants when assayed with the two cell
      lines. Our experiments fulfill such predictions. We postulate that the apparent
      hypermutability of AS52 cells probably results from a higher recovery of multi
      locus deletion mutants in AS52 cells than in K1-BH4 cells, rather than a higher
      yield of induced mutants. Preliminary studies, using Southern blot and the
      polymerase chain reaction to analyze the mutational spectrum of the mutants,
      support our hypothesis that reactive oxygens induce deletion mutations in
      mammalian cells.

PMID- 1973851
TI  - Cytogenetic assays in genotoxic studies: somatic cell effects of benzene and
      germinal cell effects of dibromochloropropane.
AB  - We have reviewed the results of our cytogenetic studies to evaluate the
      usefulness of these assays in genotoxic studies. In one study, we observed
      unusual dose-response in lymphocyte chromosome aberration frequencies after
      exposure of mice to low doses of a chemical mixture (benzene, chloroprene,
      epichlorohydrin, and xylene). The frequency in the high dose group is lower than
      those of the medium and low dose groups. This reduction of genotoxicity is
      correlated with a significant induction of a detoxifying enzyme, glutathione-S
      transferase. The data also suggest that extrapolation of effects from high to low
      doses for risk assessment may be erroneous. Using benzene as a model clastogen,
      we found that the clastogenic effect persists for a long time after termination
      of exposure in mice. This phenomenon is probably due to a gradual release of
      benzene from absorption of the chemical in body fat. In an inhalation study, we
      observed that chromosome aberrations are induced in mice after exposure to
      benzene at below the occupational exposure limit of 1 ppm. Since benzene is a
      ubiquitous environmental contaminant, it may interact with other environmental
      agents to modify its genotoxic effects. We found that a nongenotoxic drug,
      praziquantel, and a free radical scavenger, DMSO, can enhance or reduce
      respectively the clastogenic activities of benzene in mice. Both modifying agents
      acted by altering the metabolic pathways of benzene. In a study with rats, we
      showed that carcinogenic doses of benzene can induce chromosome aberrations in
      lymphocytes of rats long before the expression of cancer. With
      dibromochloropropane, we observed that this chemical can induce dominant
      lethality in rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1973852
TI  - Long-term assays for carcinogenicity.
AB  - During the past two decades, the rodent bioassay for detection of chemical
      carcinogens has reached a high standard of performance with both an increased
      number of animals and dose levels and a more detailed assessment of findings.
      However, the basic principles of testing and evaluation of results have remained
      essentially unchanged. Problems such as the length of the testing, use of maximum
      tolerated dose (MTD), selection of strains, variability of spontaneous tumors,
      discordant results between mouse and rat, and the classification of chemical
      carcinogens according to their mechanism of action have all remained unsolved. By
      contrast, the results of short-term tests and of other biological analyses do not
      always show a direct correlation with those of the long-term bioassays; this can
      be interpreted as an indication of different mechanisms of carcinogenicity.
      Currently available medium-term tests may detect carcinogenic activity of
      chemicals at particular organs in a period of time (weeks to months) relatively
      shorter than that of the 2-year carcinogenesis bioassay, and they may also
      provide additional information on mechanisms of carcinogenicity.

PMID- 1973853
TI  - Genetic activity profiles in the testing and evaluation of chemical mixtures.
AB  - Some knowledge of the potential genetic activity of a complex environmental
      mixture may be gained from an assessment of the genetic activity of its component
      chemicals. The expanded Genetic Activity Profile (GAP) data base provides a
      computer-generated graphic representation of genetic bioassay data as a function
      of dose of the substance tested. In addition, the Atmospheric Chemical Compound
      (ACC) data-base contains information on chemical structures, properties,
      detection methods, and sources of chemicals found in ambient air. Using the
      combined data bases, the quantity of an individual chemical present within a
      mixture or fraction of a mixture may be related to the quantity (lowest effective
      dose, LED) of the chemical, by itself, required to demonstrate a positive
      response in one or more genetic bioassays.

PMID- 1973854
TI  - Prediction of toxicological interactions in a binary mixture by using pattern
      recognition techniques: proposed approach with a developed model.
AB  - A model has been suggested to predict the nature of toxicological interaction in
      binary mixtures. The approach uses the NLM-HSDB computerized data bases, the
      ATSDR toxicologic profiles, and other literature for categorizing the nature
      (synergistic, antagonistic or no interaction) and degree of interaction.
      Multivariate modeling (pattern recognition techniques) is the statistical
      approach utilized to separate groups of compounds into those that interact
      synergistically or antagonistically with a given toxic compound. Preliminary
      results indicate 1) that there are sufficient data in the literature on
      interactions to permit such modeling and 2) that in the case of carbon
      tetrachloride those compounds that interact synergistically with it are more
      similar to each other than those that interact antagonistically with respect to a
      number of structural and toxicologic parameters. This suggested approach of
      utilizing pattern recognition tools will be quite useful for regulatory agencies
      in predicting toxicological interactions occurring in complex chemical mixtures
      in the environment.

PMID- 1973855
TI  - Mutagenic and carcinogenic potency indices and their correlation.
AB  - We have analyzed a significant number of studies existing in the literature, in
      which the ability of different short-term tests for predicting carcinogenicity in
      rodents was investigated. We have separated these studies into two groups. In the
      better known group of studies, qualitative predictivity was investigated
      (sensitivity and specificity). In the second group of studies (analyzed in
      greater detail), positive results were examined for the correlation between
      carcinogenic potency and potency of response in a given short-term test. There is
      substantial agreement between qualitative and quantitative predictivity; both
      appear to be situated between a low and moderate level. We have analyzed the
      interesting possibility of using the quantitative approach not only for positive
      data but for combined positive and negative data as well. We have stressed that
      short-term tests of genotoxicity should be asked to predict only initiation and
      irreversible alterations in the genome and not to predict a combination of these
      events, including promotion and modulation of differentiation. Even with regard
      to only initiation, genotoxicity data should be related to comparative
      metabolism, as well as to considerations of the significance of different end
      points and structure-activity relationship data. In conclusion, the information
      coming from short-term tests of genotoxicity is probably useful but should be
      used in conjunction with other types of information and only for predicting one
      particular class of events in the entire process of carcinogenesis.

PMID- 1973856
TI  - Strategies and governmental regulations.
AB  - An overview of testing strategies for the detection of genotoxins under OECD
      Guidelines and the EEC Directive 79/831 (VI Amendment) is outlined. The viewpoint
      of the Italian National Advisory Committee on Toxicology is also presented. In
      this context, the main issues of Genetic Toxicology (e.g., role of tests, tests
      recommended, classification of mutagens) are discussed.

PMID- 1973857
TI  - New structural concepts for predicting carcinogenicity in rodents: an artificial
      intelligence approach.
AB  - The Computer Automated Structure Evaluation (CASE) method for studying structure
      activity relationships has been applied to a data base of rodent carcinogens. It
      has been demonstrated that CASE is able to identify determinants embedded in the
      molecular structure which, with a high probability, predict rodent
      carcinogenicity. CASE has also identified determinants associated with the
      activity of non-genotoxic carcinogens, thereby suggesting that there is a
      structural commonality in the activity of these molecules. The present study
      reveals that there are "universal" as well as species-specific structural
      determinants of carcinogenicity. CASE was able to predict the carcinogenicity in
      rodents of certain endogenous pesticides in edible plants.

PMID- 1973858
TI  - Tumor promotion: models and assay systems.
AB  - Tumor promotion is defined operationally from two-stage models of experimental
      carcinogenesis. It is, therefore, in a strict sense, possible to identify tumor
      promoters only from such models. The development and use of in vitro two-stage
      cell transformation assays was a logical extension toward in vitro short-term
      testing for tumor promoters. Another approach is to apply mechanistic knowledge
      of the tumor promotion process in developing end points for such assays. In this
      context, we have been examining the role of blocked gap-junctional intercellular
      communication (GJIC) in tumor promotion, using in vitro and in vivo systems. Many
      promoters have been shown to block GJIC in vitro; our studies support the idea
      that inhibition of GJIC does play an important role in the promotion stage of
      BALB/c 3T3 cell transformation. In animal studies, we have shown that the rat
      liver tumor promoter phenobarbital can decrease the level of expression of the 32
      Kd gap junction protein gene specifically in liver upon systemic exposure in
      rats. Further examination of the role of GJIC in tumor promotion is indeed
      warranted. Also, deployment of in vitro GJIC and transformation assay systems
      should provide useful short-term tests for detecting tumor promoting activity of
      environmental chemicals.

PMID- 1973859
TI  - [A child with cutaneous polyarteritis].
AB  - A 14 year-old boy became seriously ill, following an upper respiratory tract
      infection, with high fever, arthralgia and arthritis, and a complete paralysis of
      the left median nerve. There was inadequate response to NSAIDS, but improvement
      with prednisone. During reduction of prednisone the boy developed painful
      erythematous swelling of the feet, subcutaneous nodules and afterwards livedo
      reticularis. Skinbiopsy confirmed the diagnosis of cutaneous polyarteritis.
      Different aspects of the disease are discussed.

PMID- 1973860
TI  - DNA polymorphism of major histocompatibility complex class II and class III genes
      in systemic lupus erythematosus.
AB  - We investigated the Taq I digested DNA restriction fragment length polymorphism
      (RFLP) of the Major Histocompatibility Complex (MHC) class II genes: HLA-DRB, 
      DQA, and the class III genes: C4 and 21-hydroxylase(CYP21) in 56 caucasoid
      patients with systemic lupus erythematosus (SLE) and 62 control subjects in order
      to define the molecular variation of these genes and their association with SLE.
      The results showed that the gene frequencies of both HLA-DR2 and -DR3 were
      significantly increased in the SLE population compared to normal subjects (DR2:
      21.4% vs 10.7% chi 2 = 4.5. DR3: 29.6% vs 13.3%; chi 2 = 8.3). A high frequency
      of C4A and CYP21A gene deletions was also found in SLE patients (SLE 52%, normals
      24%). All of 22 SLE patients, and 12 of 15 normal subjects who had C4A and CYP21A
      gene deletions had a 10.0kb Taq 1 DRB RFLP attributable to the presence of HLA
      DR3. Family studies showed linkage of C4A/CYP21A deletions with HLA-B8 and -DR3,
      and confirmed the previously demonstrated association of the HLA-B8, DR3, C4A*Q0,
      C4*B1, Bf*S, C2*C haplotype with SLE. Deletions affecting the C4A and CYP21A
      genes were the commonest cause of C4A null alleles in SLE. No strong association
      between C4 null phenotype or C4 gene deletion, as determined by RFLP, was
      observed in patients who possessed DR2.

PMID- 1973861
TI  - Southern analysis of DQw specificities with a short locus-specific pDQB141 cDNA
      probe.

PMID- 1973863
TI  - Executive summary of the International Conference on Genetic Variation and
      Nutrition.

PMID- 1973862
TI  - [The growth and morphological characteristics of undifferentiated and
      differentiated cells of the F9 mouse teratocarcinoma line].
AB  - Differentiation of the F9 cell line was induced by treating the cells with
      retinoic acid (10(-6) M) and dibutyryl cycloadenosinemonophosphate (10(-4) M).
      The population doubling time and the portion of cells in G1-phase increase and
      saturation density falls as the result of this treatment. Differentiated F9 cells
      demonstrate a decreased capacity of forming colonies in the soft agar, lose their
      capacity of proliferating at the clonal density, and acquire the limited life
      span in culture after reseeding at a high density. Some cells in the
      differentiated population retain their capacity of forming colonies in the soft
      agar and (or) of binding antibodies against the stem cell marker SSEA-1. Cells
      with the stem cell morphology were found in the course of passaging of
      differentiated cells after reseeding at a high density. These cells were able to
      differentiate after the standard procedure of the induction of differentiation
      with retinoic acid and dibutyryl cAMP. Causes of the rising and supporting of
      heterogeneity of the differentiated F9 cells are discussed.

PMID- 1973864
TI  - Genetic variation and nutrition in obesity: approaches to the molecular genetics
      of obesity.

PMID- 1973866
TI  - [Practical soldering of male precision part onto post caps].

PMID- 1973865
TI  - Lack of weight gain associated with short-term astemizole treatment.
AB  - The effect of treatment with astemizole for three weeks on weight was assessed in
      44 patients with seasonal allergic rhinitis who participated in a randomized,
      double-blind, placebo-controlled clinical trial. Astemizole 10-mg tablets and
      identical placebo tablets were used. Compared with baseline, weight increased
      significantly in astemizole-treated patients (1.07 +/- 1.39 kg; p = 0.0004);
      however, the mean change in weight in astemizole-treated patients was not
      statistically significantly different than that seen in placebo-treated patients
      (0.85 +/- 1.68 kg). No relationship was found between changes in weight and age,
      sex, initial weight, percentage of obesity, and plasma astemizole concentrations.

PMID- 1973867
TI  - Postpartum return of pituitary and ovarian activity during lactation inhibition
      with the new dopamine agonist CV 205-502 and during normal lactation.
AB  - The new nonergot dopamine agonist CV 205-502 appears to be a promising
      alternative in the treatment of hyperprolactinemia. Regarding the potential use
      of CV 205-502 in infertility practice, we studied the influence of CV 205-502 on
      the return of endocrine fertility parameters during the physiological
      hyperprolactinemia of the puerperium. The resumption of pituitary and ovarian
      activity in 18 CV 205-502 treated women was compared with that in 10
      bromocriptine-treated women. LH was measured by a new specific assay, which does
      not cross-react with hCG. This assay was also used in a second part of the study
      in which the pituitary function of 10 breast-feeding women was investigated. Both
      dopamine agonists adequately suppressed PRL. Pituitary secretion returned in the
      second week and was initially characterized by a high FSH/LH ratio. There were no
      major differences between CV 205-502 and bromocriptine. Ovulations occurred from
      day 18 on. The PRL rebound at the end of treatment seemed to play a role in the
      ovulation process. An acute increase of PRL just before midcycle was able to
      prevent ovulation. Breastfeeding women showed a delayed return of pituitary
      secretion: after a hypogonadotropic period, FSH returned in the third week and
      was followed by a period with a high FSH/LH ratio and follicular inactivity.

PMID- 1973868
TI  - Vitamin E deficiency and psychomotor dysfunction in adults with primary biliary
      cirrhosis.
AB  - The purpose of this study was to determine the prevalence of vitamin E deficiency
      in adults with chronic cholestatic liver disease and to quantify the association
      between their psychomotor performance and vitamin E status. In 42 female patients
      with primary biliary cirrhosis, 43.5% met two standard criteria for vitamin E
      deficiency. Vitamin E-deficient patients performed less well than did healthy
      control subjects on six of eight neuropsychologic tests of psychomotor capacity
      (p less than 0.01). Vitamin E-sufficient patients did not differ significantly
      from normal control subjects. Serum vitamin E concentrations were significantly
      lower in the group classified as significantly psychomotor-impaired by two
      independent neuropsychologists (blind to vitamin E status) whereas liver-injury
      measures failed to distinguish between these two groups. Patients with low serum
      vitamin E exhibited clinically evident neurologic abnormalities. These data
      suggest that vitamin E deficiency may, in part, underlie psychomotor and
      neurologic disturbance found in adult patients with chronic cholestatic liver
      disease.

PMID- 1973869
TI  - Intraesophageal balloon distention versus drug provocation in the evaluation of
      noncardiac chest pain.
AB  - Intraesophageal balloon distention (IEBD) has been advocated as an effective
      provocative test for the evaluation of chest pain and dysphagia. The normal
      esophageal response to intraesophageal balloon distention is to generate a
      sustained contraction proximal to the balloon while showing a distinctive absence
      of activity distal to the balloon. We evaluated intraesophageal balloon
      distention in 62 patients with noncardiac chest pain and compared the diagnostic
      results to those obtained by using a combination of acid infusion, edrophonium
      (80 micrograms/kg iv) and bethanechol (80 micrograms/kg sq). These 62 patients
      were also compared with 10 normal volunteers who underwent intraesophageal
      balloon distention. Abnormal distal manometric activity consistent with spasm and
      was seen in 38/62 (61%) patients. Distal manometric activity was not seen in any
      normal volunteer. Diagnostic results (symptom reproduction with manometric
      changes but without EKG changes) were seen in 26/62 (42%) patients, but in nine
      of the 62 (14%) patients with combined drug provocation (p less than 0.05).
      Intraesophageal balloon distention is superior to a combination of provocative
      drugs in evaluating noncardiac chest pain symptoms. The presence of abnormal
      manometric activity distal to the balloon may represent regulation of esophageal
      motility.

PMID- 1973870
TI  - The histological maturity of regenerating mucosa of healed duodenal ulcer and
      ulcer recurrence after treatment with H2-antagonist.
AB  - We investigated the relationship between the histological maturity of
      regenerating mucosa of healed duodenal ulcer and ulcer recurrence, after
      treatment with an H2-antagonist. Duodenal ulcer patients were given H2
      antagonists (either cimetidine or famotidine) for 4 wk of therapy. Fifty-two
      (77.6%) of the 67 patients were healed endoscopically. The histological state of
      the regenerating mucosa of healed duodenal ulcer was divided into three
      categories: good, fair, and poor patterns. Of the 52 healed patients, 15 achieved
      a good histological pattern. None of these 15 patients had a recurrence 3 months
      later. However, nine of the 37 patients with a fair or poor pattern of
      regenerating mucosa had a recurrence 3 months after healing (p = 0.034). We
      concluded that a duodenal ulcer should be treated until the regenerating mucosa
      of the healed ulcer reaches a good histological pattern, so as to prevent the
      recurrence of the ulcer.

PMID- 1973871
TI  - Beta-adrenergic receptor blockade in the management of pregnant women with mitral
      stenosis.
AB  - Twenty-five pregnant women with symptomatic mitral valve stenosis (mean valve
      area, 1.1 +/- 0.25 cm2) were managed by initiation or modification of beta
      adrenergic receptor blockade with the use of either propranolol or atenolol.
      Significant improvement of symptoms occurred in 23 patients (92%) (p less than
      0.01); the mean maternal heart rate was reduced significantly from 86 +/- 4 to 78
      +/- 5 beats/min (p less than 0.0001). The overall fetal heart rate ranged between
      130 to 150 beats/min during treatment. Only two patients required urgent closed
      mitral valvotomy, after pulmonary edema developed as a result of poor compliance
      to beta-blockade. All patients were safely delivered of infants at term. Fetal
      heart rates ranged between 120 to 140 beats/min at delivery. There was no
      maternal or fetal death. Pregnant woman with symptomatic mitral valve stenosis
      can be safely managed with beta-blockade, giving significant reduction in the
      incidence of pulmonary edema with no unwanted neonatal side effect.

PMID- 1973872
TI  - Expression of P-glycoprotein in epithelial ovarian cancer: evaluation as a marker
      of multidrug resistance.
AB  - The multidrug-resistance gene, MDR1, encodes a plasma membrane glycoprotein
      termed P-glycoprotein that mediates active cellular efflux of certain
      chemotherapeutic agents. P-Glycoprotein expression was evaluated in 98 frozen
      tumor specimens from 57 patients with epithelial ovarian cancer by the indirect
      immunoperoxidase technique with monoclonal antibodies C219 and JSB-1 used for
      detection. Tumor specimens were further characterized antigenically with a panel
      of monoclonal antibodies representing a variety of epithelial cell antigens.
      Included were 57 specimens from 33 previously untreated patients; 11 specimens
      were also available from eight patients in this group after chemotherapy. An
      additional 30 specimens were studied from 24 other patients after chemotherapy.
      In only four of the 57 patients with ovarian cancer (7%) did one or more of the
      specimens express P-glycoprotein. Two of these patients had tumors that were
      considered clinically drug resistant. No increase in P-glycoprotein expression
      was noted after exposure to chemotherapy, including the eight individuals for
      whom specimens were available both before and after treatment. Although drug
      resistance is a major problem in treatment of ovarian cancer, resistance to the
      drugs most active against these tumors probably occurs through a mechanism other
      than expression of the MDR1 gene product.

PMID- 1973873
TI  - Association between cardiovascular reactivity to stress and hypertension or
      behavior.
AB  - The spontaneously hypertensive rat (SHR) exhibits increased cardiovascular
      reactivity (CVR) to environmental stress and behavioral hyperactivity relative to
      the Wistar-Kyoto rat (WKY). This study sought to determine whether enhanced CVR
      to stress in the SHR is related to hypertension or to behavioral hyperactivity.
      By breeding SHR with WKY, followed by inbreeding, E. D. Hendley has developed two
      strains in which the hypertensive trait seems to be separated from the
      hyperactivity trait: the Wistar-Kyoto hypertensive (WK-HT) and the Wistar-Kyoto
      hyperactive (WK-HA) strains. Male SHR, WKY, WK-HT, and WK-HA rats were implanted
      with intravascular catheters and Doppler flow-velocity probes to record arterial
      pressure, heart rate (HR), and changes in regional vascular resistances. Five
      days after surgery, the rats were subjected to air-jet stress and pharmacological
      interventions. The hyperactive strains (SHR and WK-HA) exhibited enhanced
      pressor, renal, and mesenteric responses to stress, and higher HRs under all
      conditions, even after autonomic blockade. Both hypertension and hyperactivity
      were associated with reduced baroreceptor sensitivity. These data indicate that
      CVR to stress is related to behavioral traits.

PMID- 1973874
TI  - Arterial pH modulation of regional cerebral blood flow during hyperammonemia in
      dogs.
AB  - Acute hyperammonemia at normal arterial pH causes selective increases in midbrain
      blood flow in dogs. Unexpectedly, further increases occur with hypocapnia. We
      investigated whether metabolic acidemia and alkalemia modulate the distribution
      of ammonium across the blood-brain barrier and if, in turn, midbrain blood flow
      is effectively modulated. In dogs anesthetized with pentobarbital sodium,
      hyperammonemia (approximately 940 microM) was produced by a 210-min infusion of
      ammonium acetate. Concurrent infusion of NaHCO3 increased arterial pH to 7.53 +/-
      0.02 (SE), whereas HCl infusion decreased pH to 7.11 +/- 0.01. Normocapnia was
      maintained. Cerebrospinal fluid [HCO3-] increased 5 mM with alkalemia (one-half
      of the increase in blood) and was unchanged with acidemia. Thus cerebrospinal
      fluid [H+]/blood [H+] was greater with alkalemia than acidemia. The corresponding
      ratio for ammonium was likewise greater with alkalemia (0.70 +/- 0.06) than
      acidemia (0.44 +/- 0.08). Microsphere-determined blood flow to midbrain more than
      doubled in the alkalemic group but was unchanged in the acidemic group. No other
      region along the neuraxis or in cerebrum showed increased blood flow in either
      hyperammonemic group. Alkalemia without hyperammonemia did not increase midbrain
      blood flow. Thus metabolic acidemia-alkalemia significantly alters ammonium
      partitioning into cerebrospinal fluid, and this alteration is sufficiently great
      to exert a specific physiological effect manifested by changes in midbrain blood
      flow.

PMID- 1973875
TI  - Halothane anesthesia causes active flow-independent pulmonary vasoconstriction.
AB  - We utilized multipoint pulmonary vascular pressure-flow (P/Q) plots to
      investigate the effects of halothane anesthesia on the pulmonary circulation. Our
      first objective was to assess the extent to which the P/Q relationship measured
      in conscious dogs is altered during halothane anesthesia. P/Q plots were
      constructed by stepwise constriction of the thoracic inferior vena cava to
      decrease venous return and Q. Compared with conscious dogs, halothane
      (approximately 1.2% end-tidal) resulted in active, flow-independent pulmonary
      vasoconstriction (P less than 0.01) at all levels of Q. Halothane also decreased
      (P less than 0.01) systemic arterial pressure and Q. Thus our second objective
      was to determine whether the halothane-induced pulmonary vasoconstriction was
      mediated by reflex neurohumoral activation or by metabolites of the
      cyclooxygenase pathway. However, the magnitude of halothane-induced pulmonary
      vasoconstriction was not significantly reduced by sympathetic alpha
      adrenoreceptor block, angiotensin converting-enzyme inhibition, combined arginine
      vasopressin V1 + V2 receptor block, or by cyclooxygenase inhibition. Finally,
      halothane-induced pulmonary vasoconstriction (P less than 0.01) was also observed
      when compared with pentobarbital-anesthetized dogs during controlled ventilation.
      Thus, compared with the conscious state, halothane anesthesia causes active flow
      independent pulmonary vasoconstriction that is not mediated by reflex
      neurohumoral activation, by metabolites of the cyclooxygenase pathway, nor is it
      due to the effects of general anesthesia and controlled ventilation.

PMID- 1973876
TI  - Neuroleptic drugs and the sigma receptor.

PMID- 1973877
TI  - The sham of treatment.

PMID- 1973878
TI  - [Middle-latency auditory evoked potentials during high-dose opioid analgesia].
AB  - Neuropsychological and neurophysiological investigations indicate that a 30-40 Hz
      oscillatory brain mechanism is necessary for the adequate uptake and processing
      of elementary successive sensory events. An oscillatory component of that
      particular frequency range can be observed in the mid-latency auditory evoked
      potential (MLAEP). It is suppressed under non-specific anesthetic agents (agents
      not acting on specific structures of the brain or receptors). Opioids produce
      analgesia, sedation, and are also used for induction and maintenance of general
      anesthesia. The effect of opioids on MLAEP has not yet been examined
      sufficiently. Because intraoperative wakefulness and awareness is not rarely
      observed under high-dose opioid analgesia, the effect of general anesthesia with
      fentanyl on MLAEP and auditory evoked neuronal 30-40 Hz oscillation was studied.
      Following informed consent in 20 patients scheduled for elective surgery,
      anesthesia was induced with fentanyl 0.01-0.02 mg/kg i.v. Auditory evoked
      potentials (AEP) were recorded before and 5 min after the start of general
      anesthesia over the vertex (positive) and mastoids on both sides (negative).
      Auditory clicks were presented binaurally at 70 dBnHL with a frequency of 9.3 Hz.
      Using the electrodiagnostic system Pathfinder I (Nicolet Co.), 1000 successive
      stimuli were averaged over a 100-ms post-stimulus period and analyzed off-line.
      Latencies of the peaks V, Na, and Pa were measured. By Fast-Fourier Transform
      analysis corresponding power spectra were calculated to analyze energy portions
      of the AEP frequency components. In the awake state AEP showed an oscillatory
      component between 20- and 100-ms post-stimulus latency. Corresponding power
      spectra indicated a dominant 30-40 Hz frequency.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1973879
TI  - [The importance of high-dose alpha-receptor blockade for blood volume and
      hemodynamics in pheochromocytoma].
AB  - This prospective clinical study evaluates the possible beneficial effects of
      increased phenoxybenzamine dosage in the preoperative treatment of patients with
      pheochromocytoma. For this purpose total blood volume (TBV) prior to and after
      treatment with phenoxybenzamine and hemodynamic changes during surgery were
      determined in two groups of patients: group I (n = 12) received a mean dosage of
      140 mg, group II (n = 12) 270 mg/day. The mean TBV in group I showed no changes
      after treatment with phenoxybenzamine, while the TBV in group II increased by 5.6
      ml/kg body weight, corresponding to an increase in plasma volume (PV) of 10.2%.
      These changes were not significant, however. The intraoperative vasodilator
      requirement for the treatment of catecholamine induced hypertension during tumor
      manipulation was significantly less for group II: total nitroprusside
      administration averaged 8.7 mg in group I and 0.8 mg in group II (P less than
      0.0005). Patients in group I received a total of 2.6 mg nitroglycerin compared
      with only 0.5 mg for patients in group II (P less than 0.005). In conclusion,
      preoperative treatment of patients with pheochromocytoma with increased dosages
      of phenoxybenzamine is beneficial to intraoperative management by decreasing
      hemodynamic instability due to tumor manipulation and following resection. This
      treatment was effective for preventing complications such as excessive
      tachycardia, cardiac arrhythmias, hypertensive crises, or left ventricular
      failure.

PMID- 1973880
TI  - Effect of dexmedetomidine, a selective and potent alpha 2-agonist, on cerebral
      blood flow and oxygen consumption during halothane anesthesia in dogs.
AB  - The effect of the alpha 2-agonist dexmedetomidine on the cerebral blood flow
      (CBF) and the metabolic rate for oxygen was studied by a sagittal sinus outflow
      technique in dogs during halothane anesthesia. Dexmedetomidine was given in a
      dose (10 micrograms/kg) reported to reduce the anesthetic requirement of
      halothane by 90%. During 0.9% halothane anesthesia dexmedetomidine caused a
      significant reduction in CBF without influencing the metabolic rate for oxygen.
      Reducing the halothane concentration to 0.1% caused no further change in CBF, but
      increased the metabolic rate for oxygen 19%. The cerebral vasoconstrictive
      effect, combined with the 90% reduction in MAC for halothane, indicates that
      dexmedetomidine might be a useful adjunct to inhalation anesthetics during
      neurosurgery in situations where an increase in CBF should be avoided.

PMID- 1973881
TI  - Vecuronium for rapid-sequence intubation for cesarean section.
AB  - Because succinylcholine may occasionally be contraindicated for rapid-sequence
      induction in parturients, we studied the use of vecuronium in 21 patients having
      elective cesarean sections. Eleven patients (group 1) received 10 micrograms/kg
      vecuronium as a priming dose, followed 4-6 min later by 100 micrograms/kg. Ten
      patients (group 2) received 200 micrograms/kg vecuronium as a bolus. Onset, the
      time from the injection of vecuronium to maximal twitch suppression, and clinical
      duration, the time between vecuronium administration and return to 25% of the
      control twitch height, were recorded. Umbilical and maternal venous blood samples
      at delivery were analyzed for vecuronium concentrations. One-minute and 5-min
      Apgar scores and 1- and 24-h Neurologic and Adaptive Capacity Scores (NACS) were
      recorded. Individual tests of passive and active tone within the overall NACS
      profile were compared to evaluate further any residual vecuronium effects in the
      infants. Onset of neuromuscular blockade was 177 s in group 1 and 175 s in group
      2. The corresponding clinical durations were 73 and 115 min. Maternal and
      umbilical venous vecuronium concentrations were 515 and 73 ng/mL in group 1 and
      838 and 107 ng/mL in group 2. Seventy percent of neonates in group 1 had Apgar
      scores greater than 7 at 1 min, with 100% greater than 7 at 5 min. Corresponding
      values in group 2 infants were 50% and 80%. Fifty percent of group 1 infants had
      NACS of 35-40 at 1 h, and 70% at 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1973882
TI  - Vancomycin enhances the neuromuscular blockade of vecuronium.

PMID- 1973883
TI  - Preoperative H2-receptor antagonists.

PMID- 1973884
TI  - HLA-D region genomic polymorphism associated with Takayasu's arteritis.
AB  - Takayasu's arteritis, with a strong predilection for women and particular
      geographic areas, has revealed significant association with human lymphocyte
      antigens (HLA) specificities. In the present study, the authors investigated for
      the first time the association of Takayasu's arteritis and HLA at the genomic
      level. By use of a restriction endonuclease Taq-I and a DQA cDNA probe, HLA-D
      region restriction fragment length polymorphism was examined in 32 Japanese
      patients. It was revealed that 65.6% of the patients shared a 6.6 kb fragment,
      although this fragment was found in 35.3% of the healthy Japanese (Chi square:
      6.07, p less than 0.02). This finding suggest that HLA-D region gene variations
      determine susceptibility to Takayasu's arteritis.

PMID- 1973885
TI  - Extracorporeal photopheresis in the treatment of AIDS-related complex: a pilot
      study.
AB  - OBJECTIVE: To determine side effects of extracorporeal photopheresis in the
      treatment of patients with the acquired immunodeficiency syndrome (AIDS)-related
      complex, and to gain early evidence of efficacy of the treatment. DESIGN:
      Uncontrolled trial. SETTING: Tertiary referral center. PATIENTS: Five patients
      with AIDS-related complex: three homosexual men and one man and one woman with
      histories of intravenous drug abuse. One patient, a homosexual man, withdrew from
      therapy after 5 months but returned for monthly clinical and laboratory
      evaluations. INTERVENTION: Monthly treatments with extracorporeal photopheresis.
      MEASUREMENTS AND MAIN RESULTS: Symptoms resolved in four patients.
      Lymphadenopathy disappeared in all five. Four patients had delayed
      hypersensitivity reactions to skin testing (as defined by the Walter Reed staging
      classification). All showed increases in p24 and gp120 antibody levels. The CD4
      cell percentage increased in four patients and declined in one after 6 months of
      therapy, but the absolute CD4 count decreased in two patients. At 15 months, the
      CD4 percentage remained at or increased over the baseline value in three patients
      still in the study but decreased in one. Levels of Beta 2-microglobulin decreased
      or remained stable in four patients. All patients were culture positive for the
      human immunodeficiency virus (HIV) before treatment. One patient had a negative
      viral culture after 5 months of treatment with confirmation. Two other patients
      became HIV culture negative, one at 14 and one at 15 months: The former patient
      became positive at 15 months and the latter patient remained negative at 16
      months. CONCLUSIONS: The preliminary results suggest that extracorporeal
      photopheresis deserves further evaluation as therapy for AIDS-related complex.

PMID- 1973887
TI  - Contribution of changing rhythmicity of hypothalamic neurotransmitter function to
      female reproductive aging.

PMID- 1973886
TI  - Development of non-Hodgkin lymphoma in a cohort of patients with severe human
      immunodeficiency virus (HIV) infection on long-term antiretroviral therapy.
AB  - OBJECTIVE: To describe the incidence of non-Hodgkin lymphoma in a group of
      patients with symptomatic human immunodeficiency virus (HIV) infection receiving
      long-term dideoxynucleoside antiretroviral therapy. DESIGN: We examined the
      records of all patients with the acquired immunodeficiency syndrome (AIDS) or
      severe AIDS-related complex who were entered into three long-term phase I trials
      of zidovudine (azidothymidine, AZT) or zidovudine-containing regimens at the
      National Cancer Institute between 1985 and 1987. SETTING: The Warren G. Magnuson
      Clinical Center, National Institutes of Health, Bethesda, Maryland. PARTICIPANTS:
      Fifty-five HIV-infected patients with AIDS or severe AIDS-related complex.
      MEASUREMENTS AND MAIN RESULTS: Eight of fifty-five patients (14.5%; 95% CI, 6.5%
      to 26.7%) developed a high-grade non-Hodgkin lymphoma of B-cell type, a median of
      23.8 months (range, 13 to 35 months) after starting antiretroviral treatment.
      Using the method of Kaplan and Meier, the estimated probability of developing
      lymphoma by 30 months of therapy was 28.6% (CI, 13.7% to 50.3%) and by 36 months,
      46.4% (CI, 19.6% to 75.5%). The patients who developed lymphoma had less than 100
      T4 cells/mm3 for a median of 17.8 months (range, 7 to 35 months) and less than 50
      T4 cells/mm3 for a median of 15.3 months (range, 5.5 to 35 months) before the
      diagnosis. All patients presented with non-Hodgkin lymphoma in extranodal sites,
      and two developed primary brain involvement in the setting of Toxoplasma
      infection. CONCLUSION: Patients with symptomatic HIV infection who survive for up
      to 3 years on antiretroviral therapy may have a relatively high probability of
      developing non-Hodgkin lymphoma. Prolonged survival in the setting of profound
      immunosuppression with substantial T4-cell depletion is probably an important
      factor in the development of these lymphomas. However, a direct role of therapy
      itself cannot be totally discounted. As improved therapies for the treatment of
      HIV infection and its complications result in prolonged survival, non-Hodgkin
      lymphoma may become an increasingly significant problem.

PMID- 1973888
TI  - Vasomotor flushes.

PMID- 1973889
TI  - Glutamate dysfunction and selective motor neuron degeneration in amyotrophic
      lateral sclerosis: a hypothesis.
AB  - Recent studies provided evidence for a generalized defect in glutamate metabolism
      in patients with amyotrophic lateral sclerosis, associated with widespread
      alterations in the central nervous system levels of this excitatory amino acid
      putative transmitter. Present data support the hypothesis that altered
      presynaptic glutamatergic mechanisms may be responsible for a neuroexcitotoxic
      cell loss in this disorder. High local concentrations of glycine, released from
      glycinergic terminals, may disrupt adaptive processes contributing to abnormal
      potentiation of excitatory transmission mediated by glutamate receptors and
      resultant selective degeneration of motor neurons. These considerations offer new
      therapeutic strategies for amyotrophic lateral sclerosis.

PMID- 1973890
TI  - Clathrin and associated assembly and disassembly proteins.

PMID- 1973892
TI  - [Red soft coral-induced allergic symptoms observed in spiny lobster fishermen].
AB  - Among spiny lobster fishermen on the Pacific coast of Miyazaki Prefecture, the
      authors found two cases with bronchial asthma due to occupational sensitization
      with red soft corals (Dendronephthytia nipponica). In this report are presented
      these two cases, and the results of further investigation from allergic viewpoint
      on 72 subjects of the same occupation. Among these fishermen, such symptoms as
      sneezing, nasal discharge, cough, asthmatic attacks, conjunctival hyperamia, and
      dermatitis on removal of catches (red soft corals) from a dragnet were seen
      during spiny lobster fishing season, from September to mid-April. These symptoms
      did not develop on days when no soft corals (marine coelenterate) were caught in
      the lobster net. From a survey conducted with questionnaires all subjects of
      fishermen had conjunctival and skin manifestations, 9% of them had bronchial
      asthma and 39% of them complained of symptoms of rhinitis on exposure to red soft
      corals. Intracutaneous test with red soft coral extract in the asthmatic
      fishermen showed strongly positive for immediate and delayed type reactions,
      whereas in ten asthmatics engaged in other occupation negative for delayed
      reaction and occasionally positive for immediate reaction. And in all of five
      healthy subjects the cutaneous reaction of both types were quite negative. These
      findings suggest that red soft corals are both allergenic and irritating to
      humans. The allergic reactions due to red soft corals are considered to be a kind
      of occupational allergy that has arisen from alterations in work condition.

PMID- 1973891
TI  - Recombinant DNA and surgery.
AB  - We have the ability to isolate DNA from tissue, determine its base-pair sequence,
      and ask if a gene of interest is present. DNA strands can be isolated from one
      type of cell or organism, cleaved, and inserted (recombined) with DNA from
      another cell or organism. Recombinant DNA techniques have already improved health
      care by providing clinically useful quantities of pure human protein hormones
      such as erythropoietin, insulin, and growth hormone. Furthermore these techniques
      may increase our understanding of cellular growth control mechanisms to a level
      that was previously unattainable. They will also increase our knowledge of the
      development of major diseases and provide a means of specific nontoxic therapies
      for these diseases. Surgeons will need to understand basic DNA research
      terminology to keep up with the revolution in medical therapies that these
      techniques will cause. Our purpose is to begin the process of linking surgery to
      DNA.

PMID- 1973893
TI  - Are there neuropsychologic manifestations of the gene for Huntington's disease in
      asymptomatic, at-risk individuals?
AB  - It has recently been reported that persons at risk for Huntington's disease who
      test positive for the linked restriction fragment length polymorphism on
      chromosome 4 display neuropsychologic impairments when compared with at-risk
      subjects who test negative for this marker. We have studied a substantially
      larger series of at-risk subjects who have been thoroughly screened for the
      absence of neurologic or psychiatric features of Huntington's disease and have
      undergone predictive DNA testing. No evidence of cognitive or emotional
      differences between marker-positive and marker-negative individuals was found.
      Consideration of the designs and findings of the two studies indicates that it is
      premature to conclude that there are neuropsychologic impairments in Huntington's
      disease that precede the clinical onset of the illness.

PMID- 1973894
TI  - Irreversible modification of the voltage-sensitive calcium channel by N
      ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ).
AB  - N-Ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) inhibited, in vitro, the
      specific binding of three structurally distinct L-type Ca2+ channel ligands,
      (+)[3H]PN 200,110, [3H]desmethoxyverapamil and [3H]cis-diltiazem to guinea pig
      ileal longitudinal smooth muscle. Maximum tension responses to Ca2+ in a K(+)
      depolarized functional smooth muscle preparation were reduced in a concentration
      dependent manner following pretreatment with EEDQ and washout. Microsomal
      membranes prepared from smooth muscle pretreated with EEDQ followed by extensive
      washout showed a significant reduction in the amount of (+)[3H]PN 200,110 bound
      without change of ligand affinity. Similar results were obtained in cardiac
      ventricle microsomes. Preincubation with verapamil (1 x 10(-5) M) largely
      prevented this reduction in [3H]PN 200,110 binding sites by EEDQ. 45Ca2+ uptake
      in cortical synaptosomes during 1-sec depolarization following 68.5 mM K+ was
      also inhibited by EEDQ. Specific binding of [125I]omega-conotoxin GVIA to rat
      cerebral cortex membranes was inhibited by EEDQ, also in an apparently
      irreversible manner as seen by the marked reduction in binding site density with
      no significant change in the KD value. These observations indicate that EEDQ
      blocks Ca2+ channel function and reduces irreversibly both 1,4-dihydropyridine
      and omega-conotoxin GVIA binding sites.

PMID- 1973895
TI  - Alteration in the function of cerebral neurotransmitter receptors during the
      establishment of alcohol dependence: neurochemical aspects.
AB  - Chronic alcohol treatment induces a variety of effects on the metabolism of
      neurotransmitters and the function of their receptors. Recent studies on alcohol
      dependence and/or functional tolerance to alcohol have clearly demonstrated that
      neurotransmitter-gated and receptor-coupled ion channels, as well as
      neurotransmitter receptor coupled with intracellular mediator systems, such as
      phosphatidylinositides and cyclic nucleotide-generating systems, are invariably
      suppressed during alcohol dependence. Future studies on the central actions of
      alcohol and on alcohol dependence should therefore be directed at the molecular
      changes in synaptic membrane-bound components such as neurotransmitter receptors,
      as well as on neurotransmitter release and relevant membrane-bound enzymes.

PMID- 1973896
TI  - Neuronal mechanisms of ethanol sensitivity.
AB  - Lesion studies have suggested that different behavioural effects of ethanol are
      separate behavioural phenomena, caused by specific effects of ethanol on separate
      and independent neuronal mechanisms. Such a conclusion can also be drawn from
      behavioural studies showing that the AT (Alcohol Tolerant) and ANT (Alcohol
      Nontolerant) rat lines selected for differential ethanol-induced motor
      impairment, do not differ in all components of ethanol intoxication. Furthermore,
      neurochemical work has demonstrated differences in the functioning and the
      sensitivity to ethanol in catecholaminergic and GABAergic mechanisms between the
      lines, suggesting a role for both of these systems in the control of ethanol
      induced motor impairment.

PMID- 1973897
TI  - Interaction of ethanol and stress: research with experimental animals--an update.
AB  - Research on the interaction of ethanol (ET) and stress published since 1981 is
      reviewed. Chronic physical stressors were found to increase the ingestion of ET
      compared to nonstressed animals. With foodshock, ingestion of ET decreased during
      the stress session but rose afterwards. The elevation of ET ingestion produced by
      daily immobilization was long-lasting and was related to individual initial
      preference for ET. Psychological stressors also increased ingestion of ET. In rat
      colonies, dominant rats ingested less ET, whereas submissive rats had the highest
      intake. Factors that modify the ingestion of ET include neonatal experience and
      REM sleep deprivation. Early weaning increased, while postnatal handling
      decreased preference for ET. The effect of postnatal handling may be influenced
      by genetics. Stress, applied during adult life or prenatally, modifies some, but
      not all, the acute effects of ET. There were marked individual differences in the
      interaction of ET and stress with respect to ingestion of ET. Conversely, ET may
      modify stress-induced behavioural and neurochemical changes. This interaction may
      be stressor specific. Some stressors increase the ET's effects, whereas others
      may decrease or not affect them. In brain, ET has been shown to lessen the stress
      induced decrease in noradrenaline and 5-hydroxytryptamine (serotonin) levels and
      those in noradrenaline turnover and alpha 1-receptor binding. Stress-induced
      changes in plasma catecholamines, corticosterone, non-esterified fatty acids and
      amino acids, and in the decline in adrenal catecholamines are also lessened by
      pretreatment with ET. Possible mechanisms for the ET-stress interaction are
      discussed. These include mediation via the GABA-benzodiazepine-ionophore complex,
      endogenous opioids, the hypothalamo-pituitary-adrenocortical axis and the
      noradrenergic system.

PMID- 1973898
TI  - Narcotic analgesics.

PMID- 1973899
TI  - [Current concepts of asthma in children].
AB  - At the end of this quick survey of asthma in children we can only emphasize: The
      less than diagnostic characteristics of this syndrome, often ignored and so not
      considered. This explain perhaps, in part the current increase in frequency. The
      often precocious characteristics of the first manifestations right in the middle
      of the development of the respiratory tree. Of the need to make a team by
      associating the parents, the family physician and the allergy specialist, a team
      to which the child should be added as soon as possible. Of the multiplicity of
      factors that cause asthma, which embrace syndromes that are very personal to each
      patient and require special consideration for each, without stereotype or a
      chain.

PMID- 1973900
TI  - Identification of the K99 (F5) fimbrial adhesin in commercial vaccines used
      against calf enteritis.
AB  - A monoclonal antibody (Mab)-based antigen capture enzyme-linked immunosorbent
      assay (ELISA) was developed and standardised for the detection of the K99 adhesin
      of Escherichia coli in aqueous vaccines. A repeating epitope on the K99 antigen
      is first captured then detected using peroxidase-labelled antibody. The assay
      gave positive results with all the vaccines tested that were known to contain K99
      and was specific, rapid and reproducible.

PMID- 1973901
TI  - CRM+ haemophilia A due to a missense mutation (372----Cys) at the internal heavy
      chain thrombin cleavage site.
AB  - We have used the polymerase chain reaction (PCR) and differential oligonucleotide
      melting to screen for mutations in selected CpG dinucleotides in the factor VIII
      genes of haemophilia A patients. By this means we have identified and confirmed
      by sequencing a novel point mutation in codon 372 (CGC) of the factor VIII gene
      of a moderately severe CRM+ haemophiliac. The first C of this codon has been
      substituted by T resulting in the non-conservative substitution of cysteine for
      arginine at an essential thrombin cleavage site in factor VIII. Analysis of three
      intragenic restriction fragment length polymorphisms was uninformative in the
      patient's family. However, DNA analysis for the specific mutation shows one
      sister and the patient's mother to be carriers, and the other sister to be
      normal. This DNA analysis confirmed the results of phenotype analysis by factor
      VIII coagulant to von Willebrand factor antigen ratios for the females at risk.
      The two carrier females had low factor VIII coagulant activity and excess VIII
      antigen as predicted but the non-carrier sister also had anomalously high VIII
      antigen in her plasma. When feasible, mutation specific DNA analysis is able to
      resolve the difficulties posed by variable phenotype data and unknown level of
      mutation in sporadic haemophilia A.

PMID- 1973902
TI  - An infrequent DNA polymorphism associated with severe von Willebrand's disease.
AB  - Genomic DNA of six unrelated Dutch patients with severe von Willebrand's disease
      (vWD) was submitted to restriction fragment length polymorphism analysis. We
      observed a strong association between a 36 kb allele detected by a partial
      complementary DNA probe (pvWF 1100) and the restriction enzyme XbaI with severe
      von Willebrand's disease. This 36 kb allele is rare (allele frequency of 7%) both
      in the general population and in patients with autosomal dominant types of von
      Willebrand's disease. Three of our six patients were found to be homozygous for
      this allele while two others were heterozygous. The association of this rare XbaI
      allele with severe vWD enables carrier detection and prenatal diagnosis in these
      families. The high frequency (67%) of the 36 kb allele observed in this patient
      group raises the possibility that a subgroup of patients with severe vWD has a
      genetic defect with a common origin.

PMID- 1973903
TI  - Hysterical conversion and dissociation arising as a complication of behavioural
      psychotherapy treatment of obsessive-compulsive neurosis.
AB  - The case history of a patient with obsessive-compulsive disorder who developed
      hysterical conversion and dissociative symptoms during exposure treatment is
      described. The theoretical implications of this finding are discussed.

PMID- 1973904
TI  - Evidence against close linkage of unipolar affective illness to human chromosome
      11p markers HRAS1 and INS and chromosome Xq marker DXS52.
AB  - The genetic basis of various subtypes of the affective disorders has been
      investigated by family, twin, and adoption studies, as well as by segregation and
      linkage analysis. Linkage analyses of bipolar disorder with the chromosome 11p15
      DNA markers HRAS1 and INS, and the chromosome Xq28 markers for color blindness
      and G6PD have been reported. We have used restriction fragment length
      polymorphisms as markers to examine linkage in three extended families with
      unipolar affective illness, ascertained through probands with either recurrent
      unipolar or bipolar II illness. Using an inclusive definition of the affected
      phenotype, linkage could be excluded up to 28cM around the HRAS1-INS linkage
      group on chromosome 11p15, and up to 5 cM around the DNA marker DXS52 on Xq28.
      Negative linkage results were also obtained for two more restrictive definitions
      of affective illness. Thus, we find no evidence for the involvement of the
      chromosomal regions 11p15 and Xq28 with unipolar affective disorder in these
      three families.

PMID- 1973905
TI  - Cortisol and growth hormone responses to the 5-HT1A agonist gepirone in depressed
      patients.
AB  - The 5-HT1A agonist properties of gepirone were used to test for effects on serum
      cortisol levels in humans, 90 min after a 10 mg oral dose. Fourteen patients with
      major depression were tested in a single-blind, within-subjects, placebo design.
      Serum cortisol levels were significantly higher 90 min after gepirone compared to
      placebo (p less than 0.05). Baseline Hamilton depression ratings were correlated
      with the serum cortisol levels after acute administration of gepirone (r = 0.54,
      p less than 0.05), but not placebo. Cortisol levels after a 10 mg gepirone
      challenge were significantly (p less than 0.02) attenuated after 3-6 weeks
      chronic administration of gepirone. These preliminary findings suggest that
      relatively low doses of gepirone may stimulate human cortisol secretion in
      depressed patients, and cortisol levels after gepirone challenge may correlate
      with depression severity. Furthermore, a desensitization to gepirone's effects on
      cortisol may occur after chronic gepirone administration.

PMID- 1973906
TI  - Localization of vasodepressor neurons in the caudal ventrolateral medulla in the
      rabbit.
AB  - The precise distribution of vasodepressor neurons in the caudal ventrolateral
      medulla has been mapped in the rabbit using very small injections of L-glutamate
      (0.5 nmol in 25 nl or 0.1 nmol of 10 nl of Ringer solution). The vasodepressor
      neurons are discretely located in a circumscribed region of the lateral reticular
      formation, ventral and ventrolateral to the nucleus ambiguus, from 0.5 mm to 2.5
      mm caudal to the obex. The results indicate that the vasodepressor neurons in the
      caudal ventrolateral medulla are confined to a relatively limited region, not
      corresponding to any defined nucleus.

PMID- 1973908
TI  - Self-injection of neuroleptics.

PMID- 1973907
TI  - Twelve hours' bronchodilating effect of inhaled formoterol in children with
      asthma: a double-blind cross-over study versus salbutamol.
AB  - Thirteen children, mean age 10.9 yr, with perennial asthma, were studied with
      respect to the duration of the bronchodilating effect of formoterol, a new long
      acting beta 2 agonists for inhalation. The duration of action of formoterol
      metered dose aerosol (12 micrograms) was compared with salbutamol metered dose
      aerosol (200 micrograms) in a double-blind cross-over study. Formoterol was found
      to have significantly better bronchodilating effect 8 hr (P less than 0.01) and
      12 hr (P less than 0.05) after inhalation of the drug. Formoterol (24 micrograms)
      was given single-blindly on the third trial day and showed a tendency towards a
      better bronchodilating effect (n.s.) than formoterol (12 micrograms). There was
      no difference between the treatments with regard to adverse reactions such as
      tremor, palpitations, raised heart rate or anxiety. Formoterol proved to be
      superior to salbutamol as a long-acting bronchodilator in children with bronchial
      asthma.

PMID- 1973909
TI  - [Determinism, indeterminism, homeostasis and functional organization of the
      nervous visceral system].

PMID- 1973910
TI  - Beta 2-adrenoceptors in human lung and peripheral mononuclear leukocytes of
      untreated and terbutaline-treated patients.
AB  - Beta 2-adrenoceptor agonists act against bronchoconstriction by stimulating beta
      2-adrenoceptors in bronchial smooth muscle. However, tachyphylaxis has been
      argued to occur because of beta 2-adrenoceptor down-regulation following therapy
      with beta 2-adrenergic agents. To investigate receptor alterations, human
      peripheral mononuclear leukocytes are frequently used, since human lung tissue is
      not easily available. In order to study whether beta 2-adrenoceptors in MNL
      reliably reflect the conditions in the human lung tissue, we compared MNL and
      human lung tissue of 18 patients who had to undergo lung resection. Ten patients
      were untreated, and eight had bronchodilator therapy prior to therapy with
      terbutaline because of bronchoconstriction. Both in human lung and MNL, the beta
      2-adrenoceptor subpopulation was characterized by competition experiments with
      the beta 1-selective antagonist CGP 207.12 A and the beta 2-selective antagonist
      ICI 118.551. In MNL, a significant decrease in the density of beta 2
      adrenoceptors was found in treated but not in untreated patients, while the
      antagonist affinity of the beta 2-adrenoceptors remained unchanged. However, in
      lung parenchyma, which was obtained at the very same time from the same patients,
      no down-regulation of the total amount of beta 2-adrenoceptors could be measured.
      It is concluded that MNLs are a reliable model for studying properties of beta 2
      adrenoceptor regulation. However, the hereby obtained results show that MNLs do
      not reflect the conditions of beta 2-adrenoceptors in human lung tissue. Human
      lung tissue is found to be less susceptible than human MNL for beta 2
      adrenoceptor down-regulation by terbutaline treatment at therapeutic
      doses.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1973911
TI  - Chronotropic response of spontaneously beating mouse atria to various
      concentrations of glucose.
AB  - The effect of different concentrations of glucose on the chronotropic activity of
      isolated mouse atrial preparations was studied. It was found that glucose in the
      concentrations from 2.2 X 10(-2)M to 8.8 X 10(-2)M was ineffective to change the
      chronotropic activity of isolated mouse atria. Moroever, the effects of
      bethanechol and norepinephrine on the chronotropic activity of isolated atria
      were not modified in the presence of 8.8 X 10(-2)M glucose. However, it was
      observed that the presence of high glucose did in fact reduce the contraction
      amplitude, and in the presence of 8.8 X 10(-2)M, glucose, the contraction
      amplitude was reduced to almost 50% of its initial contraction amplitude in the
      bathing medium containing 1.1 X 10(-2)M glucose. Possibility to explain such
      phenomenon is discussed.

PMID- 1973912
TI  - Immunocytochemical study of endocrine cells in pelvic ileal reservoirs.
AB  - The distribution and morphology of intestinal endocrine cells was investigated in
      the mucosa of pelvic ileal reservoirs using immunocytochemical methods.
      Endoscopic biopsies were obtained from 15 patients after the construction of a
      modified J-pouch. The mucosa of the reservoir showed a variable degree of colonic
      metaplasia in all cases. No relevant quantitative variations of gut endocrine
      cells were detected, as revealed by immunostaining for the general marker,
      chromogranin, compared with normal ileal mucosa. Immunostaining for different
      peptide-containing cells resulted in normal number and morphology of serotonin,
      enteroglucagon, peptide tyrosine-tyrosine, and somatostatin-containing cells.
      Neurotensin cells were less numerous than in normal mucosa. The role played by
      gastrointestinal hormones in the adaptive response of the intestine to pouch
      construction is, presently, unclear. Further studies involving measurements of
      fasting and meal-stimulated levels of gut hormones in pouch patients might
      clarify this aspect.

PMID- 1973914
TI  - Structural analysis of human thyroid hormone receptor beta gene.
AB  - Thyroid hormone receptors (TR) are ligand-dependent, DNA-binding, trans-acting
      transcriptional factors belonging to the erbA-related steroid/thyroid hormone
      receptor superfamily. To better understand the structural and functional
      characteristics of TRs, we isolated the gene encoding human TR beta 1 (hTR beta
      1). The coding region of hTR beta 1 is split into at least eight exons. Each exon
      well correlates with functional domains of hTR beta 1 protein, and the
      exon/intron organization is highly conserved when compared with the chicken c
      erbA gene which encodes an alpha-type chicken TR. We demonstrate that hTR beta
      has at least two mRNA forms having different lengths of the 3' untranslated
      region. We also note several nucleotide corrections of hTR beta 1 cDNA sequence.

PMID- 1973913
TI  - Hep-G2 glucose transporter gene polymorphism in Caucasian, black, Hispanic and
      Japanese patients with NIDDM.
AB  - DNA from non-diabetic Caucasians (n = 16), Blacks (n = 22), Hispanics (n = 13)
      and Japanese (n = 21), as well as DNA from 34 Caucasian, 19 Black, 19 Hispanic
      and 20 Japanese non-insulin-dependent diabetes mellitus (NIDDM) patients were
      examined for restriction fragment length polymorphism (RFLP) after digestion with
      enzymes BglII and XbaI, and hybridization with the glucose transporter probe,
      hGT2-2. There were significant differences in the incidence of the RFLPs between
      Caucasians and Blacks, both controls and patients with NIDDM. Digestion with XbaI
      revealed a higher incidence of the homozygotic state for allele I in NIDDM
      Caucasians (12 vs. 0%) than in controls. In NIDDM Blacks and Hispanics, we found
      a high incidence of a combination of two traits: 42% of the Black and 47% of the
      Hispanic NIDDM patients were homozygous for the BglII allele I and heterozygous
      for XbaI. Only 23% of non-NIDDM Blacks or Hispanics had this combination (P less
      than 0.05). There was no association between RFLP frequency and NIDDM among
      Japanese subjects. These data support the influence of race on both BglII and
      XbaI RFLPs. The homozygotes for XbaI in Caucasians and the presence of two
      specific traits in Blacks and Hispanics appear with higher frequency in NIDDM.

PMID- 1973915
TI  - [Sympathetic activity in patients with heart failure due to idiopathic dilated
      cardiomyopathy: modification by beta receptor blockers--a therapeutic approach?].
AB  - Increased sympatho-adrenergic activity is a compensatory mechanism in cardiac
      failure. Accordingly, beta-receptor blockers are generally regarded as
      contraindicated for use in heart failure. In 1975, Waagstein reported the first
      successful use of beta-receptor blockers in patients with idiopathic dilated
      cardiomyopathy. It was shown that the prognosis of patients with dilated
      cardiomyopathy could be improved by beta-receptor blockade. In this regard, most
      experience is associated with metoprolol. It should be stressed that the initial,
      and long-term dosage, as well, was maintained at a very low level (beginning, for
      example, with 6.25 mg metoprolol daily). An on-going, international, multicenter
      study is intended to clarify which patients with dilated cardiomyopathy may
      benefit from treatment with beta-receptor blockers. Additionally, further
      information is anticipated with respect to the complex mechanism of action.
      Beside the direct cardiac action with blockade of the cardiotoxic effect of the
      extremely high levels of plasma catecholamines, induction of an upregulation of
      the down-regulated beta-1-receptors there is attenuation of the activity of the
      renin-angiotensin-aldosterone system. Overall, this leads to interruption of the
      vicious cycle of maladaption associated with chronic heart failure and its
      attendant unfavorable vasoconstriction and sodium and water retention. This
      positive aspect of beta-1-receptor blockade in dilated cardiomyopathy carries
      with its initially and unavoidable negative inotropic effect and thus, in the
      individual patient, the net effect is difficult to predict. Consequently, the
      indication must be established on an individual basis.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1973916
TI  - [Chronic heart failure: improvement of the prognosis by therapy?].
AB  - There are two goals in the management of chronic heart failure: relief of
      symptoms and prolongation of life. Until recently, pharmacological interventions
      were tested primarily in order to evaluate their effects on exercise capacity and
      clinical symptoms. However, two multicenter trials have now provided evidence
      that treatment of chronic heart failure is able to improve mortality. Indeed,
      prolongation of life without improving symptoms is not desirable. The two classic
      keystones of therapy in heart failure, diuretics and digitalis, remain powerful
      agents to relieve symptoms. However, their impact on survival remains elusive,
      since no controlled studies are available which address this question with
      adequate sample size. Vasodilators such as the combination of hydralazine and
      isosorbide dinitrate and ACE-inhibitors, however, have been shown to improve
      survival in patients with moderate to severe chronic heart failure. In contrast,
      prazosin failed to be effective in this respect. More sophisticated questions
      emerge, in particular, do ACE-inhibitors or vasodilators, effectively interfere
      with the progression of the disease? May early treatment be preventive and retard
      the course of heart failure? Several large scale multicenter trials are now under
      way to address these issues.

PMID- 1973917
TI  - Minimal biliary excretion and enterohepatic recirculation of lormetazepam in man
      as investigated by a new nasobiliary drainage technique.
AB  - The pharmacokinetics of lormetazepam (LMA) was studied in five patients with
      intact and interrupted enterohepatic recirculation (EHR) after an oral dose of
      0.03 mg/kg given as solution. The disposition of lormetazepam in plasma was
      characterized by peak plasma levels of 14-60 ng/ml after 20-40 min. Peak plasma
      levels of the unchanged drug were higher (p less than 0.05) in case of
      interrupted EHR as compared to intact EHR. The areas and the plasma levels vs
      time curves of lormetazepam and its glucuronide were not statistically different
      and the oral clearance of lormetazepam was similar in both parts of the study
      (median 3.1 and 3.6 ml/min/kg). In case of interrupted EHR, 23-58% of dose was
      excreted as lormetazepam and its glucuronide with the urine during 24 h, in case
      of intact EHR, the urinary dose fraction was 9-35% (p less than 0.05). The 24 h
      postdose-bile fraction contained only 0.3-2.8% of the oral lormetazepam dose in
      form of the drug and its glucuronide. In conclusion, only negligible amounts of
      lormetazepam are excreted in bile. The demethylated metabolite lorazepam was not
      detectable in the biological samples investigated.

PMID- 1973918
TI  - Endocrinologic aspects of gestational trophoblastic diseases.

PMID- 1973920
TI  - Glucose tolerance in pregnant women following treatment for sterility.
AB  - The incidence of glucose intolerance in 76 patients with polycystic ovary disease
      (PCOD) who became pregnant after treatment for ovulation was compared with that
      in 95 healthy women, matched with respect to age and diabetic background, who
      conceived without intervention. The incidence of abnormal glucose tolerance test
      results in the treated group was twice that in the normal group (19.7% vs. 9.5%;
      P less than .03). Moreover, within the treated group abnormal test results
      occurred more frequently in patients who became pregnant following induction of
      ovulation with human menopausal gonadotropin (29%) than in those who conceived as
      a result of other treatment modalities (12%).

PMID- 1973919
TI  - The causes of high-order multiple gestation.
AB  - Most recent reviews of multiple gestations have reported that the major cause of
      triplet and quadruplet pregnancy is therapy with human menopausal gonadotropin
      (hMG). In an attempt to decrease the number of high-order multiple gestations due
      to hMG, serial ovarian ultrasound evaluation was introduced in the mid-1970s. To
      assess the impact of changing technology on the causes of high-order multiple
      gestation, we reviewed the experience at our institution from 1983 to 1987.
      During this time period, 35,119 deliveries were performed, including 13 triplet
      and 2 quadruplet deliveries. Of the triplet and quadruplet pregnancies, 3 (20%)
      patients conceived spontaneously, 11 (73%) conceived in association with
      ovulation induction, and 1 (7%) conceived during an IVF cycle. Of the pregnancies
      associated with ovulation induction, 9 (82%) were associated with clomiphene
      therapy and only 2 (18%) with hMG therapy. Of the clomiphene patients, 6 (67%)
      conceived at a dose of 50 mg per day for five days and 5 (55%) conceived during
      the first cycle. At the present time, in our institution, hMG therapy is no
      longer the major cause of triplet and quadruplet pregnancies. It is possible that
      serial serum estradiol and ovarian ultrasound monitoring of hMG cycles has
      contributed to the low number of hMG-induced triplet and quadruplet pregnancies
      that we observed.

PMID- 1973921
TI  - Fertility after bilateral tubal pregnancy--modern treatment considerations.
AB  - A case of microscopically proven bilateral ectopic pregnancy (EP) is described.
      Salpingectomy and linear salpingostomy were performed. Shortly after recovery
      from surgery for EP, another conception occurred.

PMID- 1973922
TI  - Cervical cerclage--its role in the pregnant anomalous uterus.
AB  - Twenty-nine cases of cervical incompetence were found among 98 women diagnosed as
      having a congenital uterine anomaly on hysterosalpingography, a high incidence of
      30%. The highest incidence was found in the bicornuate uterus group--38%. The
      incidence of premature delivery and late abortion was higher in this group than
      in the rest of the patients with uterine anomalies (55% and 68%, vs. 45% and
      32%). An obvious improvement in obstetrical performance was noted after cerclage.
      In the cervical incompetence group, term deliveries increased from 26% to 63%.
      Premature deliveries and late abortions dropped from 74% to 37%. Even in the
      patients with anomalous uterus without proven diagnosis of cervical incompetence,
      term deliveries increased from 64% to 96%, and pregnancies terminating
      prematurely dropped from 35.6% to 4%, following cerclage. No doubt exists as to
      the need for cerclage in cases of cervical incompetence. We also believe it
      should be performed prophylactically in cases of bicornuate uterus. The concept
      of routine prophylactic cerclage in all cases of uterine anomalies should be
      considered.

PMID- 1973923
TI  - Effect of calcium-modifying drugs on mouse in vitro fertilization and
      preimplantation development.
AB  - Calcium ions are required for normal in vitro fertilization and preimplantation
      development in the mouse. This study examined the effects of alterations in Ca2+
      flux and distribution on sperm penetration of eggs and embryo cleavage. Compounds
      used included diltiazem, a Ca2+ channel blocker, and 8-(N,N-diethylamino)octyl
      3,4,5-trimethoxybenzoate (TMB-8), an antagonist of intracellular calcium release.
      Incubation of sperm and eggs with diltiazem at 30 and 10 microM and TMB-8 at 30,
      10, and 3 microM resulted in depressed fertilization compared with controls.
      Motility was not inhibited at these concentrations of either drug. Both drugs
      also depressed progression of mouse embryos from 2-cell to blastocyst at 30 and 3
      microM concentrations. This study suggests that both Ca2+ flux and distribution
      to specific cellular sites are required for normal mouse in vitro fertilization
      and early preimplantation development.

PMID- 1973925
TI  - Effect of vasectomy on the ultrastructure of epididymal epithelium in rhesus
      monkey.
AB  - Ultrastructural changes in the epididymal epithelium and the fate of accumulating
      spermatozoa were examined in the vasectomized rhesus monkey (Macaca mulatta).
      Accumulation of spermatozoa resulted in an increase in the diameter of the tubule
      and its lumen. Ultrastructure of principal cells revealed that they continue to
      perform both secretory and absorptive functions after vasectomy. The rough
      endoplasmic reticulum, Golgi complex, and mitochondria were well developed in the
      principal cell. Bulging of the apical portion of principal cells and membrane
      bound structures in the lumen suggests an increase in apocrine secretion. An
      increase in the number of vesicles, vacuoles, and multivesicular bodies in the
      principal cells indicates an increased absorptive activity. Increased absorptive
      function was also evident in the apical cells. Macrophages with sperm remnants
      were seen in the lumen, and occasionally in the connective tissue. The principal
      or only mechanism of sperm disposal after vasectomy appeared to be intraluminal
      endocytosis by macrophages.

PMID- 1973924
TI  - A comparison of microsurgery and laser surgery for ovarian wedge resections.
AB  - To evaluate the effect of microsurgery and CO2 laser on postoperative adhesion
      formation after ovarian wedge resection, 30 New Zealand adult female rabbits were
      randomly divided into three groups of ten animals each. The control group (n =
      10) had ovarian wedge resections using a scalpel with closure of the ovary
      performed using microsurgery technique. The second group had ovarian wedge
      resections performed using the CO2 laser coupled to an operating microscope. The
      third group (n = 10) had multiple small areas of vaporization performed on the
      ovary using the CO2 laser. Four weeks after the initial surgery the animals were
      killed and evaluated for intraperitoneal adhesions. No significant differences (P
      greater than .05) were found between the three groups of animals. This study
      suggests that the use of laser surgery may not offer a significant reduction in
      postoperative adhesion formation in comparison with standard microsurgery
      technique when performing ovarian wedge resections.

PMID- 1973926
TI  - At law. One flew over the Supreme Court.

PMID- 1973928
TI  - Relationship between changes in buoyant density and formation of new sites of
      cell wall growth in cultures of streptococci (Enterococcus hirae ATCC 9790)
      undergoing a nutritional shift-up.
AB  - When the glutamate concentration of cultures of Enterococcus hirae was raised
      from 20 to 300 micrograms/ml, the mass doubling time decreased from ca. 85 to 45
      min in 9 min, but balanced growth was not reestablished for 30 to 40 min. During
      the unbalanced period of growth, RNA and protein synthesis proceeded more rapidly
      than did peptidoglycan synthesis, buoyant density increased from ca. 1.1024 to
      1.1075 g/ml, and the rate of formation of new cell wall growth sites transitorily
      accelerated above the new growth rate. When studied as a function of cell size,
      all cultures showed buoyant density to decrease around cell separation, increase
      as cells increased in size, and then plateau when cells reached large volumes.
      Greater increases in buoyant density as a function of cell size were seen after
      shift-up, with the greatest increases observed at 15 to 20 min after shift-up,
      when the rate of formation of new sites was also maximal. In a population of
      cells examined by electron microscopy 15 min after shift-up, buoyant density and
      the frequency of cells with new sites increased as old sites approached the size
      of two poles. These data were consistent with a model whereby buoyant density
      increases in the terminal stages of the cell cycle when the surface grows slower
      than the cytoplasm. The greater the difference in the rates of inside to outside
      growth, the greater the increase in buoyant density and the more frequently new
      sites will be initiated.

PMID- 1973927
TI  - Identification, cloning, and sequencing of piv, a new gene involved in inverting
      the pilin genes of Moraxella lacunata.
AB  - Moraxella lacunata is a bacterium that is a causative agent of human
      conjunctivitis and keratitis. We have previously cloned the Q and I pilin
      (formerly called beta and alpha pilin) genes of Moraxella bovis and determined
      that an inversion of 2 kilobases (kb) of DNA determines which pilin gene is
      expressed. Using an M. bovis pilin gene as a hybridization probe to screen a
      lambda ZAP library of M. lacunata DNA, we have isolated a clone that not only
      contains the entire type 4 pilin gene inversion region of M. lacunata but inverts
      the 2-kb region on a plasmid subclone (pMxL1) in Escherichia coli. Deletion
      derivatives of pMxL1 yielded some plasmids that still had the entire inversion
      region but were phase locked into one or the other of the two potential
      orientations. Similarly, insertions of a 2-kb streptomycin-resistant element
      (omega) within some regions outside of the inversion also resulted in phase
      locked plasmids. These deletions and insertions thus localize a probable
      invertase necessary for the inversion event. The region was sequenced, and an
      open reading frame with over 98% DNA sequence homology to an open reading frame
      that we previously found in M. bovis and called ORF2 appeared to be a strong
      candidate for the invertase. This conclusion was confirmed when a plasmid
      containing the M. bovis ORF2 supplied, in trans, the inversion function missing
      from one of the M. lacunata phase-locked inversion mutants. We have named these
      putative invertase genes piv(ml) (pilin inversion of M. lacunata) and piv(mb)
      (pilin inversion of M. bovis). Despite previously noted sequence similarities
      between the M. bovis sites of inversion and those of the Hin family of invertible
      segments and a 60-base-pair region within the inversion with 50% sequence
      similarity to the cin recombinational enhancer, there is no significant sequence
      similarity of the Piv invertases to the Hin family of invertases.

PMID- 1973929
TI  - Purification and properties of glutamine synthetases from the cyanobacteria
      Synechocystis sp. strain PCC 6803 and Calothrix sp. strain PCC 7601.
AB  - Glutamine synthetases (GSs) from two cyanobacteria, one unicellular
      (Synechocystis sp. strain PCC 6803) and the other filamentous (Calothrix sp.
      strain PCC 7601 [Fremyella diplosiphon]), were purified to homogeneity. The
      biosynthetic activities of both enzymes were strongly inhibited by ADP,
      indicating that the energy charge of the cell might regulate the GS activity.
      Both cyanobacteria exhibited an ammonium-mediated repression of GS synthesis. In
      addition, the Synechocystis sp. showed an inactivation of GS promoted by ammonium
      that had not been demonstrated previously in cyanobacteria.

PMID- 1973930
TI  - Nucleotide sequence of Escherichia coli asnB and deduced amino acid sequence of
      asparagine synthetase B.
AB  - The Escherichia coli asparagine synthetase B gene (asnB) has been cloned into a
      temperature-sensitive, low copy plasmid, pOU71, as shown by the complementation
      of an E. coli asparagine auxotroph, E. coli JE6279. The nucleotide sequence of
      asnB and the flanking sequences were determined. The proposed coding region for
      the gene is 1662 nucleotides in length, and the deduced amino acid sequence of
      the coding region results in a protein that has a molecular weight of 62,666 and
      contains 554 amino acids. A promoter region is identified based on the
      transcription start site that was determined by primer extension experiments.
      Homology studies of the asnB protein sequence with the human asparagine
      synthetase and E. coli asparagine synthetase A protein show that there is a high
      degree of homology with only the human asparagine synthetase. A purF type
      glutamine amide transfer domain was identified upon inspection of the amino
      terminal amino acid sequence of the asparagine synthetase B protein.

PMID- 1973931
TI  - Cerebral metabolism of [1,2-13C2]acetate as detected by in vivo and in vitro 13C
      NMR.
AB  - The metabolism of [1,2-13C2]acetate in rat brain was studied by in vivo and in
      vitro 13C NMR spectroscopy, in particular by taking advantage of the homonuclear
      13C-13C spin coupling patterns. Well nourished rats were infused with [1,2
      13C2]acetate or [1-13C]acetate in the jugular vein, and the in situ kinetics of
      13C labeling during the infusion period was followed by 13C NMR techniques. The
      in vivo 13C NMR spectra showed signals from (i) the C-1 carbon of [1,2-13C2]
      acetate or [1-13C]acetate, (ii) 13CO3H-, and (iii) the natural abundance 13C
      carbons of sufficiently mobile fatty acids. Methanol/HCl/perchloric acid extracts
      of the brains were prepared and were further analyzed by high resolution 13C NMR.
      The homonuclear 13C-13C spin coupling patterns after infusion of [1,2
      13C2]acetate showed very different isotopomer populations in glutamate,
      glutamine, and gamma-aminobutyric acid. Analyzing the relative proportions of
      these isotopomers revealed (i) two different glutamate compartments in the rat
      brain characterized by the presence and absence, respectively, of glutamine
      synthase activity, (ii) two different tricarboxylic acid cycles, one
      preferentially metabolizing [(1,2-13C2]acetate, the other mainly using unlabeled
      acetyl-coenzyme A, (iii) a hitherto unknown cerebral pyruvate recycling system
      associated with the tricarboxylic acid cycle, metabolizing primarily unlabeled
      acetyl-coenzyme A, and (iv) a predominant production of gamma-aminobutyric acid
      in the glutamate compartment lacking glutamine synthase.

PMID- 1973932
TI  - Solution structure of neurotoxin I from the sea anemone Stichodactyla helianthus.
      A nuclear magnetic resonance, distance geometry, and restrained molecular
      dynamics study.
AB  - The three-dimensional structure of the sea anemone polypeptide Stichodactyla
      helianthus neurotoxin I in aqueous solution has been determined using distance
      geometry and restrained molecular dynamics simulations based on NMR data acquired
      at 500 MHz. A set of 470 nuclear Overhauser enhancement values was measured, of
      which 216 were used as distance restraints in the structure determination along
      with 15 dihedral angles derived from coupling constants. After restrained
      molecular dynamics refinement, the eight structures that best fit the input data
      form a closely related family. They describe a structure that consists of a core
      of twisted, four-stranded, antiparallel beta-sheet encompassing residues 1-3, 19
      24, 29-34, and 40-47, joined by three loops, two of which are well defined by the
      NMR data. The third loop, encompassing residues 7-16, is poorly defined by the
      data and is assumed to undergo conformational averaging in solution. Pairwise
      root mean square displacement values for the backbone heavy atoms of the eight
      best structures are 1.3 +/- 0.2A when the poorly defined loop is excluded and 3.6
      +/- 1.0A for all backbone atoms. Refinement using restrained molecular dynamics
      improved the quality of the structures generated by distance geometry
      calculations with respect to the number of nuclear Overhauser enhancements
      violated, the size of the total distance violations and the total potential
      energies of the structures. The family of structures for S. heliathus neurotoxin
      I is compared with structures of related sea anemone proteins that also bind to
      the voltage-gated sodium channel.

PMID- 1973934
TI  - The clinical course and long-term management of generalized anxiety disorder.
AB  - Evidence suggests that generalized anxiety disorder (GAD) has a fairly chronic
      course marked by significant long-term distress and comorbidity. Research has
      focused on short-term treatment of GAD, and long-term outcome studies after
      either short- or long-term treatment have been relatively neglected. The authors
      discuss the benefits and risks of various drug and nondrug therapies used in the
      long-term management of generalized anxiety disorder and suggest avenues for
      future research.

PMID- 1973933
TI  - Application of a computer-assisted high-performance liquid chromatographic multi
      wavelength ultraviolet detection system to simultaneous toxicological drug
      analyses.
AB  - An emergency drug screening system for the separation and identification of toxic
      drugs, MULTI-HPLC, is presented. Chromatographic peaks, which were impossible to
      identify with a conventional high-performance liquid chromatographic UV detection
      system, became distinguishable by the spectral search and retention prediction of
      the data-processing program MCASYST. Sixty-five toxic drugs, frequently
      identified in drug poisionings in Japan, were selected as references in the drug
      library. Retention time, optimum detection wavelength, detection limit and
      recoveries from serum and urine were listed. Possible applications of the system
      are demonstrated, using gastric contents, sera and urines in cases of multiple
      drug ingestion. Quantitative analysis was sufficiently sensitive and precise to
      permit clinical diagnosis with increased accuracy.

PMID- 1973935
TI  - Differential effect of gepirone on presynaptic and postsynaptic serotonin
      receptors: single-cell recording studies.
AB  - The sustained administration of the serotonin (5-hydroxytryptamine1A, 5-HT1A)
      agonist gepirone (15 mg/kg/day subcutaneously) in the rat produced an initial
      decrease of the firing activity of dorsal raphe 5-HT neurons, which was followed
      by a progressive recovery to normal after 14 days of treatment. At this point,
      the somatodendritic 5-HT1A autoreceptor had desensitized, as indicated by the
      reduced effectiveness of intravenous lysergic acid diethylamide (LSD) and of
      microiontophoretic applications of 5-HT, LSD, 8-hydroxy-2-(N,N-propylamino)
      tetralin (8-OH-DPAT), and gepirone, but not of gamma-aminobutyric acid in
      depressing the firing activity of 5-HT neurons. In contrast, the responsiveness
      of postsynaptic dorsal hippocampus pyramidal neurons to 5-HT, 8-OH-DPAT, and
      gepirone was not altered by the 14-day gepirone treatment. In an attempt to
      unravel the differential effect of sustained gepirone administration on
      presynaptic and postsynaptic 5-HT1A receptors, the properties of gepirone at
      these two receptors were assessed. The concurrent microiontophoretic application
      of gepirone readily blocked the effect of 5-HT on dorsal hippocampus pyramidal
      neurons, but not on dorsal raphe 5-HT neurons, thus indicating that gepirone is a
      partial agonist at postsynaptic 5-HT1A receptors and a full agonist at
      somatodendritic 5-HT1A receptors. It is proposed that gepirone, being a partial
      agonist at postsynaptic 5-HT1A receptors, fails to desensitize them; whereas,
      because of its full agonistic activity at the somatodendritic 5-HT1A receptor, it
      desensitizes this autoreceptor with long-term administration.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1973936
TI  - Azapirones: history of development.
AB  - The azapirones, a unique pharmacologic class that includes buspirone and gepirone
      appear to offer the promise of both antidepressant and anxiolytic activity. Their
      singular affinity for the serotonin (5-hydroxytryptamine [5-HT]) type 1A (5-HT1A)
      receptor subtype may be the factor responsible for the therapeutic activity of
      these agents. It is hoped that the distinctive characteristics of this new class
      of drugs will lead to effective therapy for the treatment of mood disorders
      without the adverse or ancillary effects associated with currently available
      agents such as the benzodiazepines. The development of drugs for the treatment of
      anxiety has gradually evolved from less selective agents, such as alcohol,
      opiates, and the bromides, to progressively more specific drugs, leading
      ultimately to the development of the benzodiazepine anxiolytics in 1959. The
      approval of the azapirone buspirone in 1986 marked a new era of psychotherapeutic
      drug therapy. There is now evidence that this new generation of anxiolytic drugs
      may offer antidepressant potential in addition to its anxiolytic properties.

PMID- 1973937
TI  - Neuroendocrine effects of azapirones.
AB  - In healthy volunteers, the azapirones--buspirone, ipsapirone, and gepirone-
      increase plasma cortisol and decrease body temperature; buspirone and gepirone
      also increase plasma prolactin and growth hormone. Data from animal studies
      suggest that the ability of azapirones to decrease body temperature and increase
      corticotropin and corticosterone is mediated by stimulation of presynaptic and
      postsynaptic serotonin (5-hydroxytryptamine, 5-HT) type 1A subtype receptors,
      respectively. The mechanism of altered growth hormone and prolactin secretion is
      less clear. While animal studies implicate changes in dopamine function, current
      human investigations suggest that 5-HT1A receptors also may be involved in these
      endocrine responses. Further investigations, using more selective 5-HT receptor
      antagonists, will be required to resolve this issue.

PMID- 1973938
TI  - Abuse potential of buspirone and related drugs.
AB  - Scientific evidence regarding the drug abuse potential of buspirone and gepirone
      is reviewed. In animal studies, the pharmacologic profile of buspirone differs
      from that of other classes of abused drugs. Buspirone does not share
      discriminative stimulus effects with abused depressants, and it is not self
      administered. New data are presented showing a lack of reinforcing effects for
      gepirone in rhesus monkeys when the drug was evaluated in an intravenous drug
      self-administration procedure. Studies of the acute effects of buspirone
      conducted in human subjects provide no evidence of abuse potential, and there is
      no indication that the drug has been abused to any extent since being marketed in
      December 1986. Available evidence suggests that the azapirones buspirone and
      gepirone have little, if any, potential for abuse.

PMID- 1973939
TI  - A double-blind comparison of buspirone, clobazam, and placebo in patients with
      anxiety treated in a general practice setting.
AB  - Sixty patients being treated for anxiety in a primary care facility received
      (double-blind) buspirone, the benzodiazepine drug clobazam, or placebo for 3
      weeks. The mean daily dose at the end of treatment was 23 mg for buspirone and 21
      mg for clobazam. Patients were assessed weekly using the Hamilton Rating Scale
      for Anxiety and Clinical Global Impression scale. Both active treatments produced
      significant improvement in anxiety symptoms compared with placebo as early as the
      first week of treatment, and there was progressive improvement over the
      subsequent 2 weeks. Response to buspirone was equally favorable in anxious
      patients who experienced depressive symptomatology.

PMID- 1973940
TI  - Symptom comorbidity in anxiety and depressive disorders.
AB  - The ability of the Hamilton Rating Scale for Anxiety, the Hamilton Rating Scale
      for Depression, and 50 items from the self-rated Hopkins Symptom Checklist to
      discriminate generalized anxiety disorder from major depressive disorder was
      examined for over 3,000 patients entering studies in three drug development
      projects at Bristol-Myers Squibb Company. Discriminant analysis models using
      stepwise procedures were developed for each scale separately, combining both
      Hamilton scales, and combining all three scales. The statistical model using both
      Hamilton scales produced the best discrimination. Items from the Hopkins Symptom
      Checklist scale did not improve the ability to discriminate patients by diagnosis
      correctly. The generalizability was tested by applying the discriminant models to
      new data sets or subsets of the data sets used in the model-building process.
      Correct classification rates for differentiating the two disorders ranged from 87
      99% for the final model.

PMID- 1973941
TI  - Neurochemistry and neurophysiology of buspirone and gepirone: interactions at
      presynaptic and postsynaptic 5-HT1A receptors.
AB  - Preclinical neurochemical studies indicate that buspirone and gepirone bind
      selectively to presynaptic (dorsal raphe) and postsynaptic (hippocampus, cortex)
      5-hydroxytryptamine1A (5-HT1A) receptor binding sites. Furthermore, in functional
      neurochemical and electrophysiologic receptor studies, azapirones in general
      display partial agonist activity at postsynaptic 5-HT1A receptors linked
      negatively to adenyl cyclase and appear to demonstrate a similar profile on
      hippocampal CA1 pyramidal neurons sensitive to the effects of 5-HT. Through their
      action at presynaptic 5-HT1A receptors, these agents have been shown to dose
      dependently inhibit cortical and hippocampal 5-HT synthesis while inhibiting the
      firing of 5-HT--containing dorsal raphe neurons, both in vitro and in vivo. These
      results suggest that the efficacy seen in clinical trials of anxiety and
      depression may be related to buspirone's and gepirone's complex interaction with
      presynaptic and postsynaptic 5-HT1A receptors, which initiate long-term changes
      in central 5-HT neurotransmission.

PMID- 1973942
TI  - Gepirone in the treatment of major depression.
AB  - Gepirone is a serotonin (5-hydroxytryptamine, 5-HT) type1A receptor agonist and a
      pharmacologic analogue of buspirone. Two double-blind, placebo-controlled studies
      show the efficacy of gepirone in the treatment of major depression. Study 1
      demonstrates gepirone's superiority over placebo in an 8-week acute treatment of
      patients with major depression, including the melancholic subtype. Gepirone's
      antidepressant dose range is tentatively established at 5-30 mg/day. Study 2
      reveals the benefit of gepirone compared with placebo in 4-week continuation
      therapy of patients with major depression who initially responded to 6 weeks of
      open therapy with gepirone. Analysis of Hamilton Rating Scale for Depression item
      scores show gepirone especially improves scores on items of core depression.

PMID- 1973943
TI  - Efficacy of continuation drug therapy of depression and anxiety: issues and
      methodologies.
AB  - Continuation treatment is the continued administration of a drug after
      disappearance of acute symptoms for the purpose of maintaining control over the
      episode. This critical phase of treatment constitutes a neglected area of
      research concerned with depression and anxiety disorders. Most therapeutic
      studies focus on the treatment of acute symptoms, using designs of only 4-8
      weeks' duration. These studies provide little information on the effectiveness
      and use of continuation treatment for the duration of an episode, which may
      extend for months following control of acute symptoms. Furthermore, the
      relatively few continuation drug therapy studies deal primarily with depressive
      disorders, leaving anxiety disorders almost two decades behind depressive
      disorders in terms of published research in this critical area of treatment. This
      report reviews the current status of continuation drug treatment for anxiety and
      depression and examines research needs, issues, and problems. It also presents a
      design model for evaluating the need for and duration of continuation treatment
      for both depressive and anxiety disorders.

PMID- 1973944
TI  - Obsessive-compulsive disorder: treatment with serotonin-selective uptake
      inhibitors, azapirones, and other agents.
AB  - Obsessive-compulsive disorder (OCD) has recently been recognized as a relatively
      common disorder, affecting one in 40 individuals in the United States. OCD has
      also been demonstrated to be at least partially drug-responsive, although fewer
      than 20 adequate, fully controlled treatment trials in OCD patients have been
      reported, all in the last decade. The partially selective serotonin (5
      hydroxytryptamine, 5-HT) uptake inhibitor clomipramine has been the most studied
      drug and uniformly has been found to be of some benefit in patients with OCD.
      Several recent controlled trials with other, more highly selective 5-HT uptake
      inhibitors have also shown these drugs to be more effective than placebo. More
      recently, preliminary data from several studies have questioned whether
      buspirone, an azapirone with prominent 5-HT-related anxiolytic and possible
      antidepressant properties, may have direct therapeutic effects in OCD patients or
      may be a useful adjunct when used in combination with the selective 5-HT uptake
      inhibitor fluoxetine. These studies are reviewed briefly and evaluated in the
      context of investigations that used other drugs with serotonergic actions either
      alone or in combination with selective 5-HT uptake inhibitors in OCD patients.

PMID- 1973945
TI  - Terminal sprouting is not responsible for enhanced transmitter release at disused
      neuromuscular junctions of the rat.
AB  - Chronic block of nerve-muscle activity is known to induce sprouting of motor
      nerve terminals and to enhance transmitter release at the neuromuscular junction.
      Increased transmitter release has been assumed to be a physiological correlate of
      disuse-induced sprouting of nerve terminals. We examined this assumption in the
      rat extensor digitorum longus muscle following chronic conduction block of the
      sciatic nerve with TTX. The minimal period of nerve block required for the
      expression of terminal sprouting was 3 d, whereas transmitter release, measured
      by the quantal analysis of end-plate potentials, was already enhanced within 24
      hr of nerve block. Following 6 d of nerve block, sprouting was observed in about
      35% of the motor nerve terminals examined. Under this condition, the total length
      of individual terminals was significantly greater in the terminals with sprouts
      than those without sprouts. However, enhancement of transmitter release occurred
      uniformly at these junctions regardless of the presence or absence of terminal
      sprouts. Also, transmitter release enhanced by nerve block for 2 d remained
      elevated for at least 4 d even after resumption of nerve activity without the
      formation of terminal sprouts. It is concluded that terminal sprouting and
      increased transmitter release induced in disused neuromuscular junctions are not
      causally related and that the signals for inducing these 2 events are at least
      quantitatively different.

PMID- 1973946
TI  - Glycine-insensitive NMDA-sensitive receptor expressed in Xenopus oocytes by
      guinea pig cerebellar mRNA.
AB  - The electrophysiological and pharmacological properties of N-methyl-D-aspartate
      (NMDA)-sensitive receptors expressed in Xenopus oocytes by injection of total
      poly(A)+RNAs (mRNAs) from the cerebellum and cerebrum of guinea pigs were
      compared. The inward current induced by NMDA under voltage-clamp in cerebellar
      mRNA-injected oocytes was depressed in a voltage-dependent fashion by Mg2+ to
      show a negative slope conductance and selectively antagonized by D-2-amino-5
      phosphonovalerate (D-APV) and phencyclidine (PCP). Glycine (0.01-10 microM) did
      not potentiate NMDA-induced currents in cerebellar mRNA-injected oocytes, while
      it potentiated NMDA-induced currents in cerebral mRNA-injected oocytes in a dose
      dependent fashion. 6-Cyano-7-nitroquinoxaline-2,3-dione and 7-chlorokynure-nate
      suppressed the NMDA response but significantly less potently in cerebellar mRNA
      injected oocytes than in cerebral mRNA-injected oocytes. These results suggest
      that the NMDA-sensitive receptor expressed in Xenopus oocytes by guinea pig
      cerebellar mRNA resembles the cerebral NMDA receptor in its high sensitivities to
      Mg2+, PCP, and D-APV, but it is distinct from the cerebral NMDA receptor in
      responsiveness to glycine.

PMID- 1973947
TI  - Lesions of the nigrostriatal dopamine projection increase the inhibitory effects
      of D1 and D2 dopamine agonists on caudate-putamen neurons and relieve D2
      receptors from the necessity of D1 receptor stimulation.
AB  - Extracellular single unit recording and microiontophoretic techniques were used
      to determine the sensitivities and interactions of D1 and D2 dopamine (DA)
      receptors in the caudate putamen (CPu) of rats that were denervated of DA by
      intraventricular injections of the catecholamine neurotoxin 6-hydroxydopamine (6
      OHDA). Seven to 10 d after the 6-OHDA injection, DA levels in the ipsilateral CPu
      were reduced to 11.8% of control. Current-response curves revealed that the
      inhibitory responses of CPu neurons to microiontophoretic administration of both
      the selective D1 receptor agonist SKF-38393 and the selective D2 receptor agonist
      quinpirole were significantly increased in 6-OHDA-pretreated rats, suggesting up
      regulation of both receptor subtypes. Although our previous studies have
      established that D1 receptor activation is normally required for (enables) the
      inhibitory effects of selective D2 agonists in the CPu, this requirement was no
      longer evident in 6-OHDA-denervated rats. Whereas acute DA depletion [produced by
      the tyrosine hydroxylase inhibitor alpha-methyl-p-tyrosine (AMPT)] attenuated the
      inhibitory effects of quinpirole on CPu neurons, long-term DA denervation
      (produced by 6-OHDA) enhanced the inhibitory effects of the D2 agonist. The
      enhanced effects of quinpirole in 6-OHDA-lesioned rats were not due to residual
      DA stimulating supersensitive D1 receptors (i.e., enabling) since further DA
      depletion (99.7%), produced by acute administration of AMPT in 6-OHDA-lesioned
      rats, failed to diminish the inhibitory efficacy of quinpirole. In addition to
      relieving D2 receptors from the need for D1 receptor-mediated enabling, 6-OHDA
      lesions also abolished the normal synergistic relationship between the receptor
      subtypes since low (subinhibitory) currents of SKF-38393 (4 nA) failed to
      potentiate the inhibitory effects of quinpirole on CPu neurons in lesioned rats.
      Similar findings (i.e., supersensitivity and loss of synergistic effects) were
      obtained from rats that had received repeated pretreatment with reserpine (2.5
      mg/kg) for 4 d, indicating that these effects of 6-OHDA lesions were due to the
      depletion of synaptic DA rather than to the structural loss of DA terminals.
      Therefore, both the quantitative (potentiation) and the qualitative (enabling)
      synergistic effects between D1 and D2 receptors in the rat CPu were abolished
      when these receptors were functionally supersensitive. The present study provides
      electrophysiological support for previous behavioral studies indicating that the
      requirement of D1 receptor stimulation for D2 receptor-mediated functional
      effects (enabling) is not maintained in rats chronically depleted of DA by either
      6-OHDA lesions or repeated reserpine.

PMID- 1973948
TI  - Immunocytochemical and neurochemical evidence for age-related loss of GABA in the
      inferior colliculus: implications for neural presbycusis.
AB  - The present study describes substantial, selective, age-related loss of the
      putative inhibitory neurotransmitter GABA in the central nucleus of the inferior
      colliculus (CIC) of rat based on immunocytochemical and neurochemical data. For
      immunocytochemistry, neurons in the CIC were immunolabeled using an antibody
      against a GABA conjugate in young adult (2- to 7-month-old) and aged (18- to 29
      month-old) Fischer-344 rats. Computer-assisted morphometry was then used to
      generate maps of GABA-immunoreactive neurons in the CIC. The number of GABA
      positive neurons was reduced 36% in the ventrolateral portion of the CIC of aged
      animals (93 neurons/mm2) compared to their matched young adult cohorts (145
      neurons/mm2; p less than 0.01). For neurochemistry, basal and K(+)-evoked release
      of the endogenous amino acids GABA, glutamate (Glu), aspartate (Asp), and
      tyrosine (Tyr) from micropunches of the CIC were measured in 8 age-paired animals
      from the 2 age groups using high-performance liquid chromatography. Overflow of
      radiolabeled acetylcholine (3H-ACh) was also determined. In both age groups, K(+)
      evoked release of GABA, Glu, Asp, and 3H-ACh from CIC punches was significantly
      enhanced above basal efflux (+200, +215, +163, and +309%, respectively), while
      Tyr release was unchanged. Evoked release of 3H-ACh and all amino acids except
      Tyr showed substantial Ca2+ dependence. A significant (p less than 0.05) age
      related reduction in both basal (-35%) and K(+)-stimulated (-42%) efflux of GABA
      from the CIC was observed. A corresponding decrease in postrelease tissue content
      of GABA in CIC of aged rats was observed (-30%, p less than 0.05). In contrast,
      tissue content as well as basal and evoked release of Glu, Asp, Tyr, and 3H-ACh
      was similar between the 2 age groups. Age-related GABA neurochemical changes
      described in the CIC were not observed in the release of the other amino acids or
      3H-ACh from either the rostral ventrolateral medulla or the somatosensory cortex,
      2 brain regions involved in processing non-auditory sensory input. These data
      support previous findings that GABA, Glu, Asp, and ACh may subserve
      neurotransmission in the CIC. Additionally, these data provide clear evidence for
      a pronounced, region- and neurotransmitter-selective, age-related reduction of
      GABA in the CIC. These findings support the hypothesis that impairment of
      inhibitory GABAergic neurotransmission in the CIC may contribute to abnormal
      auditory perception and processing seen in neural presbycusis.

PMID- 1973950
TI  - [Nerve tissue distribution and physiologic role of somatostatin and its
      receptor].

PMID- 1973949
TI  - The medical importance of riceland mosquitoes and their control using
      alternatives to chemical insecticides.
AB  - The medical importance, ecology and control of riceland mosquitoes using
      alternative strategies is reviewed. Over 135 pest and vector anopheline and
      culicine mosquito species found in association with riceland habitats and their
      medical importance are presented. Malaria and Japanese encephalitis are the two
      most serious human diseases transmitted by riceland mosquitoes, but they have
      been incriminated as vectors of dozens of arboviruses and other parasites and
      pathogens including the causal agents of West Nile and Rift Valley Fevers and
      lymphatic filariasis. Control of vector and pest mosquitoes using chemical
      pesticides has generated several problems including: insecticide resistance,
      safety risks for humans and domestic animals, and other environmental concerns.
      These problems and the high cost and sustainability of programs based
      predominantly on conventional insecticides have stimulated increased interest in
      integrated control measures in ricelands. The integrated pest management (IPM)
      strategy for mosquito control, also known as integrated vector control (IVC), is
      an ecologically based approach that may involve several complementary
      interventions used in combination or singly. Environmental management, and
      chemical, biological and mechanical control, comprise the elements of IVC
      proposed for use in or near riceland habitats. Some of the elements of
      environmental management include the use of intermittent irrigation; flushing of
      fields; use of rice cultivars that require less water; shifting of planting
      schedules to avoid optimal mosquito breeding conditions; relocation of
      communities or use of dry belt farming around them; and zooprophylaxis and other
      personal protection methods, especially use of insecticide-impregnated bed nets.
      Biological control agents that have been used successfully in rice fields include
      several species of larvivorous fish, a mermithid nematode (Romanomermis
      culicivorax), a fungus (Lagenidium giganteum) and bacteria (Bacillus
      thuringiensis var. israelensis and Bacillus sphaericus). The mermithid and the
      entomopathogens have demonstrated little or no adverse effects on populations of
      vertebrate and invertebrate nontarget organisms. The successful use of any
      particular method or combination of interventions for the control of riceland
      mosquitoes will depend on in-depth ecological studies on the target species and
      nontarget organisms, sound geographic reconnaissance and effective routine
      sampling and evaluation. When biological control agents are considered,
      additional background on the environmental factors limiting their efficacy will
      also be needed. In addition to the technical components of the various
      interventions employed in integrated control, sustained suppression of riceland
      mosquitoes and the diseases they transmit will require a greater sociocultural
      supportive background, particularly in developing countries.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 1973951
TI  - [Nerve tissue distribution and physiologic role of sleep peptides].

PMID- 1973952
TI  - [Neuropeptides and analgesic pharmacology].

PMID- 1973953
TI  - [Mental disorders and neuropeptides].

PMID- 1973954
TI  - [Neuropeptide and neuroendocrine research: past, present and future].

PMID- 1973955
TI  - [Sequence and classification of neuropeptides].

PMID- 1973956
TI  - [The relation between phylogeny and neuropeptides].

PMID- 1973957
TI  - [Neuropeptide as neuromodulator].

PMID- 1973958
TI  - [Neuronal regulation mechanisms of peptide neurons].

PMID- 1973959
TI  - [Neuropeptide receptor and intracellular signaling].

PMID- 1973960
TI  - [Localization and physiologic role of neuropeptides and their receptors--peptides
      of the bombesin family--GRP, neuromedin B and neuromedin C].

PMID- 1973961
TI  - [Localization and physiologic role of neurotensin and its receptor].

PMID- 1973963
TI  - [Measures for primary poison elimination in children].

PMID- 1973962
TI  - [Studies on immunoreactive somatostatin and gastrin contents of the gastric
      mucosa in patients with duodenal ulcer--comparison to patients with fundic gland
      polyposis and normal subjects].
AB  - The immunoreactive gastrin (IRG) and somatostatin (IRS) contents in gastric
      mucosa were measured from the same biopsy specimen of the same patients with
      duodenal ulcer (DU) at the active stage and healing stage, and compared to those
      of patients with fundic gland polyposis (FP) and endoscopically normal subjects
      whose gastric mucosa had only slight atrophic change (Control). The IRS in both
      the antrum and the gastric body of DU were significantly lower than those of the
      other two groups, and those showed no difference between the two stages. In all
      groups, there was a significant positive relation between the IRG and IRS in the
      antrum. In DU, particularly at the active stage, the relative decrease of the IRS
      against the IRG was prominent compared to the other two groups. In FP, which has
      similar background gastric mucosa and ability of acid output to those of DU, it
      was found that somatostatin was secreted sufficient to control gastrin secretion
      and acid output. Whereas in DU, secretion of somatostatin was reduced and,
      particularly at the active stage, it was considered that somatostatin, which
      could control increased gastrin secretion and increased acid output, was not
      secreted.

PMID- 1973965
TI  - Immunogenetic markers for autoimmune diseases of the endocrine system.
AB  - New immunogenetic markers are demonstrated for type 1 diabetes mellitus, Graves'
      disease and Hashimoto's thyroiditis. These markers are detected by restriction
      fragment length polymorphism (RFLP) analysis of HLA-D region genes and genes for
      the tumor necrosis factor alpha (TNF alpha). By analysing haplotypes transmitted
      to diabetic probands in families and comparing them with haplotypes that are only
      transmitted to healthy siblings it is shown that DQw8-DQB1 gene variation is
      important for susceptibility on DR4 haplotypes. Analysis of this DQw3 split in
      patients with Hashimoto's thyroiditis reveals that the other DQB1 gene variation,
      namely DQw7, displays the strongest association with Hashimoto's thyroiditis.
      This DQB1 variation has several implications for susceptibility and/or
      pathogenesis of both autoimmune endocrine diseases. Novel polymorphisms for TNF
      alpha are detected and it is shown that heterozygosity for TNF polymorphisms is
      significantly associated with type I diabetes and Graves' disease. Furthermore,
      DR4 haplotypes transmitted to diabetic probands possess significantly more the
      10.5 Kb fragment in contrast to DR4 haplotypes transmitted only to healthy family
      members. This genetic polymorphism raises functional issues in susceptibility to
      autoimmune disease and can lead to a new explanation of the enigmatic HLA
      association with a variety of diseases.

PMID- 1973964
TI  - Pathophysiology of autoimmune diseases.
AB  - Immune reactions towards self antigens can lead to cell destruction and
      autoimmune disease. In this review it is summarized, how autoimmune diseases are
      classified from a clinical standpoint into organ-specific and systemic
      involvement and how our understanding has evolved during recent history. The
      experimental basis is discussed with transfer models, T-cell suppressor control,
      T-cell recognition of antigen presenting cells, T-cell clones and more recent
      transgenic mouse models. It is finally concluded that autoimmunity develops due
      to the direct activation of autoreactive CD4 positive T-cells. Monoclonal
      antibodies interfering with this interaction may prove a useful immune
      intervention. However, antigens and relevant epitopes for autoimmune induction
      still need to be identified and characterized.

PMID- 1973967
TI  - Paste soldering: a new technique that eliminates guesswork.

PMID- 1973966
TI  - [AIDS and nursing. 1. European conference].

PMID- 1973968
TI  - Association of sleep apnoea with myocardial infarction in men.
AB  - To examine the hypothesis that sleep apnoea is a risk factor for ischaemic heart
      disease, overnight polysomnography was performed in 101 unselected male survivors
      of acute myocardial infarction (MI) aged less than 66 yr and in 53 male subjects
      of similar age without evidence of ischaemic heart disease. The apnoea index (AI,
      number of apnoea episodes per hour of sleep) was 6.9 (SEM 1.2) in the MI patients
      versus 1.4 (0.3) in the control subjects. After adjustment for age, body mass
      index, hypertension, smoking, and cholesterol level, multiple logistic regression
      analysis identified the top quartile of AI (greater than 5.3) as an independent
      predictor of MI patients. The relative risk for myocardial infarction between the
      highest and lowest quartiles of AI was 23.3 (95% confidence interval 3.9-139.9).

PMID- 1973969
TI  - Effects of transdermal versus oral hormone replacement therapy on bone density in
      spine and proximal femur in postmenopausal women.
AB  - 66 early postmenopausal women were randomised to 28-day cycles of either
      transdermal hormone replacement therapy--continuous oestradiol 17-beta 0.05 mg
      daily, with norethisterone acetate 0.25 mg daily for 14 of each 28 days--or oral
      therapy--continuous conjugated equine oestrogens 0.625 mg daily, with dl
      norgestrel 0.15 mg daily for 12 of each 28 days. An untreated reference group of
      30 women were studied concurrently. Bone density was measured in the lumbar spine
      and proximal femur by dual photon absorptiometry at 6-month intervals for 18
      months. Skeletal turnover was assessed by serum measurements of calcium,
      phosphate, and alkaline phosphatase, and by urine estimations of
      hydroxyproline/creatinine and calcium/creatinine excretion. In both treatment
      groups by comparison with the untreated groups by comparison with the untreated
      group, bone density increased in the vertebrae and proximal femur and biochemical
      measurements indicated a significant reduction in bone turnover.

PMID- 1973970
TI  - Effect of breast-feeding on antibody response to conjugate vaccine.
AB  - Infants were immunised at the ages of 2, 4, and 6 months with conjugate
      Haemophilus influenzae type b vaccine, and their responses to the vaccine were
      evaluated by feeding method (breast or formula). There were no significant
      differences between the groups in antibody levels at early ages. However the
      antibody levels were significantly higher in the breast-fed (57 infants) than the
      formula-fed group (24 infants) at 7 months (mean [SD] 29.8 [32.0] vs 17.5 [14.8]
      micrograms/ml) and at 12 months (55 vs 26 infants; 4.8 [4.4] vs 3.0 [2.3]
      micrograms/ml). These findings are strong evidence that breast-feeding enhances
      the active immune response in the first year of life, and therefore the feeding
      method must be taken into account in the evaluation of vaccine studies in
      infants.

PMID- 1973971
TI  - Mapping of acute (type I) spinal muscular atrophy to chromosome 5q12-q14. The
      French Spinal Muscular Atrophy Investigators.
AB  - Linkage analysis in twenty-five families with acute (type I) spinal muscular
      atrophy (SMA) showed that the mutant gene responsible for the disorder is tightly
      linked to the D5S39 locus. The mutation(s) causing the intermediate (type II) and
      juvenile chronic (type III) forms of SMA were also mapped to DNA marker D5S39 on
      chromosome 5 (5q12-q14). Thus, the three forms, which have been differentiated
      clinically on the basis of age of onset and clinical course, are most probably
      due to different mutations at a single locus on chromosome 5. Prenatal diagnosis
      of SMA type I will now be possible.

PMID- 1973972
TI  - Preliminary report: hepatic vein Doppler in the early diagnosis of acute liver
      transplant rejection.
AB  - 37 transplanted livers (in thirty patients) were assessed by serial doppler
      ultrasound examination. 18 of 23 biopsy-proved rejection episodes were associated
      with abrupt damping of the normally pulsatile blood flow of the hepatic veins. In
      the other 5 episodes, the waveforms were damped at the outset by perioperative
      ischaemia. There were no rejection episodes with normal traces. Another cause of
      damping was cholangitis (5 episodes), but this was distinguishable clinically and
      biochemically. There were no episodes of rejection with normal hepatic vein
      traces. Serial doppler examination, in combination with clinical evaluation, may
      allow earlier diagnosis and treatment of liver rejection.

PMID- 1973973
TI  - Steroids after spinal cord injury.

PMID- 1973974
TI  - Spinal muscular atrophies.

PMID- 1973975
TI  - Quinolones in acute non-travellers' diarrhoea.

PMID- 1973976
TI  - Reflux and respiratory symptoms.

PMID- 1973977
TI  - Cardiac biopsy in myocarditis.

PMID- 1973978
TI  - The second twin.

PMID- 1973979
TI  - Premature mortality due to cardiovascular disease in hypopituitarism.
AB  - 333 consecutive patients with hypopituitarism diagnosed between 1956 and 1987
      were retrospectively examined. The patients had been given routine replacement
      therapy. The overall mortality was higher than in an age and sex matched
      population. Deaths from vascular disorders were also significantly increased (60
      [40 male, 20 female] versus 30.8 expected [23.5, 7.4 female]). The hazard
      function for vascular death was independent of age at diagnosis, time after
      diagnosis, calendar year of diagnosis, gender, degree of pituitary insufficiency,
      hypertension, and diabetes mellitus. Mortality risk was raised irrespective of
      whether hypopituitarism was due to pituitary adenoma or secondary to other
      diseases. 7 patients (3 male, 4 female) died from malignant diseases (expected
      10.1 and 4.1, respectively). These observations indicate that life expectancy is
      shortened in patients with hypopituitarism. Growth-hormone deficiency could be a
      factor in this increased mortality from cardiovascular disease.

PMID- 1973980
TI  - Prevalence and sequelae of sexual torture.
AB  - 283 torture victims (135 examined by the Amnesty International [AI] Danish
      Medical Group, and 148 by the International Rehabilitation and Research Center
      for Torture Victims [RCT]) were questioned about methods of torture and
      subsequent sexual difficulties. Overall, the prevalence of sexual torture was 61%
      (women 80%, men 56%), but this was higher in the RCT than in the AI group. More
      Latin Americans than Europeans had been sexually tortured in the AI group.
      Prevalence of sexual difficulties was 32%, the RCT recording a significantly
      higher prevalence than the AI (43% vs 20%). Sexually tortured victims were more
      likely to have sexual difficulties (40%) than were non-sexually tortured victims
      (19%). Overall, there were more cases of sexual difficulties in victims from
      Africa and from Turkey/Middle East/Far East than in victims from Latin America
      and from Europe. In the RCT subsample, prevalence of sexual difficulties and
      anxiety was significantly higher in sexually tortured victims than in non
      sexually tortured victims; the two groups were broadly similar with respect to
      depression and low self-esteem. Depressed victims and victims with low self
      esteem were more likely to have sexual difficulties. In the RCT group, but not
      overall, prevalence of sexual difficulties was significantly associated with age
      but was independent of low self-esteem and of depression.

PMID- 1973981
TI  - Diagnosis of epilepsy.

PMID- 1973982
TI  - Epilepsy in old age.

PMID- 1973983
TI  - GISSI-2 and the heparin controversy.

PMID- 1973984
TI  - Compensation for heat-illness death, USA.

PMID- 1973985
TI  - More international perspectives on HIV.

PMID- 1973986
TI  - Preconception genetic diagnosis of cystic fibrosis.

PMID- 1973987
TI  - Increased relapse of duodenal ulcers in patients treated with cognitive
      psychotherapy.

PMID- 1973988
TI  - Antihypertensive activity of sinorphan.

PMID- 1973989
TI  - Visiting and immunisation policies on a regional neonatal unit.

PMID- 1973990
TI  - Infectivity of blood that is immunoblot intermediate reactive on hepatitis C
      virus antibody testing.

PMID- 1973991
TI  - Screening donors for hepatitis C virus antibody.

PMID- 1973992
TI  - Detection of hepatitis C virus RNA in serum.

PMID- 1973993
TI  - Very early intracranial haemorrhage in alloimmune fetal thrombocytopenia.

PMID- 1973994
TI  - Predictive characteristics for early mortality in patients awaiting coronary
      artery bypass.

PMID- 1973995
TI  - Hughes Day revisited.

PMID- 1973996
TI  - Thrombolytic therapy in suspected myocardial infarction.

PMID- 1973997
TI  - Oestrogens, arterial status, and postmenopausal women.

PMID- 1973998
TI  - Acute compartment syndrome secondary to theophylline overdose.

PMID- 1973999
TI  - In-vitro production of TNF-alpha in blood samples.

PMID- 1974000
TI  - Anti-motility drugs for infants.

PMID- 1974001
TI  - Postgraduate training in Italy.

PMID- 1974002
TI  - Research and ophthalmology in the UK.

PMID- 1974003
TI  - Hypothyroidism.

PMID- 1974004
TI  - Concern about bovine spongiform encephalopathy.

PMID- 1974005
TI  - Ropinirole without levodopa in Parkinson's disease.

PMID- 1974006
TI  - HTLV-I/II antibodies in UK blood donors.

PMID- 1974007
TI  - False-positive autoantibodies in HIV infection.

PMID- 1974008
TI  - Tracking AIDS epidemic in libraries.

PMID- 1974009
TI  - Death from diabetic ketoacidosis after cessation of octreotide in acromegaly.

PMID- 1974010
TI  - Prevention of diabetes in BB/Wor rats treated with monoclonal antibodies to
      interferon-gamma.

PMID- 1974011
TI  - Survival after rabies immunisation in newborn infant of affected mother.

PMID- 1974012
TI  - Paramyosin as helminth vaccine candidate.

PMID- 1974013
TI  - Symptoms of reactogenicity in field trial of oral cholera vaccine.

PMID- 1974014
TI  - Significance of crystal clear urine.

PMID- 1974015
TI  - Renal artery stenosis and peripheral vascular disease: implications for ACE
      inhibitor therapy.

PMID- 1974016
TI  - Tumour necrosis factor to treat chronic hepatitis B virus infection.

PMID- 1974017
TI  - Glycyrrhetinic acid and potentiation of hydrocortisone activity in skin.

PMID- 1974018
TI  - Pre-eclampsia and HLA-DR4.

PMID- 1974019
TI  - Rectal gluten challenge and diagnosis of coeliac disease.

PMID- 1974020
TI  - Possible locus for polycystic kidney disease on chromosome 2.

PMID- 1974021
TI  - Acquired hearing impairment and psychiatric disorder amongst Australian Vietnam
      veterans.

PMID- 1974022
TI  - Xenon for anaesthesia.

PMID- 1974024
TI  - Comment: do we need trials of agents alleged to improve healing of plantar
      ulcers?

PMID- 1974023
TI  - [Malignant somatostatinoma--diagnosis after 6 years].
AB  - Early symptoms of malignant somatostatinoma with dyspeptic complaints, moderate
      diabetes mellitus and cholecystolithiasis are the reason of primary treatment of
      these patients by surgeons. CASE REPORT: In a 34-year old patient with typical
      anamnesis of cholecystitis and moderate diabetes mellitus liver metastases were
      seen during laparotomy. In the beginning the metastases were mistaken for
      hepatocellular carcinoma histologically. There was no deterioration until June
      1988 when a high-grade stenosis of the duodenum has developed. Now a malignant
      somatostatinoma was diagnosed histologically and confirmed by immunohistology.
      Somatostatinomas are generally diagnosed by repeated measures of increased plasma
      SLI associated with decreased insulin, glucagon, pancreatic-polypeptide (PP) and
      vasoactive-intestinal-peptide (VIP). In normally or moderately increased plasma
      SLI concentrations provocation with tolbutamid may be helpful. Treatment should
      remove most of the tumor by surgical intervention, while chemotherapy must be
      less pronounced.

PMID- 1974025
TI  - Effects of ketone bodies on carbohydrate metabolism in non-insulin-dependent
      (type II) diabetes mellitus.
AB  - The ability of ketone bodies to suppress elevated hepatic glucose output was
      investigated in eight postabsorptive subjects with non-insulin-dependent diabetes
      mellitus (NIDDM). Infusion of sodium acetoacetate alone (20 mumols/kg/min) for 3
      hours increased total serum ketones (beta-hydroxybutyrate and acetoacetate) to
      approximately 6 mmol/L, but did not reduce plasma glucose (14.0 +/- 0.8 to 12.3
      +/- 0.9 mmol/L) or isotopically determined hepatic glucose output (17.5 +/- 1.4
      to 12.7 +/- 1.0 mumols/kg/min) more than saline alone. Plasma C-peptide
      concentrations were unchanged, while serum glucagon increased from 131 +/- 13 to
      169 +/- 24 ng/mL (P less than .015) and free fatty acids were suppressed by 43%
      (0.35 +/- 0.08 to 0.20 +/- 0.06 mmol/L, P less than .025). When sodium
      acetoacetate was infused with somatostatin (0.10 micrograms/kg/min) to suppress
      glucagon and insulin secretion, the decrease in both plasma glucose (13.3 +/- 0.9
      to 10.2 +/- 0.7 mmol/L) and hepatic glucose output (17.2 +/- 1.6 to 9.4 +/- 0.6
      mumols/kg/min) was greater than either acetoacetate or somatostatin infusion
      alone. Infusion of equimolar amounts of sodium bicarbonate had no effect on
      glucose metabolism. In conclusion, these results demonstrate that ketone bodies
      can directly suppress elevated hepatic glucose output in NIDDM independent of
      changes in insulin secretion, but only when the concomitant stimulation of
      glucagon secretion is prevented. Ketone bodies also suppress adipose tissue
      lipolysis in the absence of changes in plasma insulin and may serve to regulate
      their own production.

PMID- 1974026
TI  - An alternative strategy for therapy of AIDS; a cure?
AB  - Present therapeutic strategies in AIDS require continuous treatment. The
      recognition of the major contribution of an 'autoimmune' component to the
      pathology of the disease opens up the possibility of ablation of specific T-cell
      sets as a means of preventing and reversing the disease.

PMID- 1974027
TI  - Cure of duodenal ulcer after eradication of Helicobacter pylori.
AB  - Eighty-two patients, whose duodenal ulcers were recurrent or resistant to H2
      receptor antagonist therapy, were entered in a treatment protocol of ranitidine
      followed by a four-week "triple therapy" course to eradicate Helicobacter pylori
      (HP) infection. The triple therapy consisted of colloidal bismuth subcitrate,
      tetracycline and metronidazole. Duodenal ulcer healed in all 78 patients
      available for endoscopy and H. pylori infection was shown to be eliminated in 75
      patients (96%) at rebiopsy four weeks after cessation of therapy. In these 75
      remaining patients the relapse rates for H. pylori infection and duodenal ulcer
      were studied endoscopically, yearly and at any recurrence of symptoms. At Year 1,
      71 of 73 patients remained free of H. pylori infection (HP-negative) and duodenal
      ulcer. The corresponding figures subsequently were: Year 2, 57/57; Year 3, 34/34;
      Year 4, 15/15. No duodenal ulcers recurred in HP-negative patients who were
      followed for up to four years. Two patients of the original cohort of 75 HP
      negative patients were HP-positive with endoscopic duodenitis at 12 months, and
      one at 36 months, but all were without reulceration. Distorted duodenal caps
      gradually returned to near-normal appearance in 80% of patients by two years.
      From this four-year follow-up study we conclude that duodenal ulcer disease will
      not recur provided the patient remains free of H. pylori.

PMID- 1974028
TI  - Cardiac failure following Irukandji envenomation.
AB  - This paper presents a case of Irukandji syndrome (envenomation by the jellyfish,
      Carukia barnesi) with pulmonary oedema and hypokinetic cardiac failure. This case
      highlights the need for victims (and operators of tours venturing into the waters
      of North Queensland) to treat even apparently innocuous stings with vinegar and
      to avoid freshwater bathing and rubbing of stings immediately after such
      incidents. It also reinforces the use of phentolamine to treat the symptoms of
      catecholamine release associated with the syndrome. This patient required
      inotropic support and further underlines the need for practitioners to be aware
      that the syndrome can have severe sequelae and that central venous monitoring and
      inotropic management should be available when treating Irukandji stings.

PMID- 1974029
TI  - [Changes in the prostanoid content and the population of endocrine cells in
      jejunal biopsies from celiac children].
AB  - Prostanoid content prostaglandin E2 (PGE2) and thromboxane B2 (TxB2) and
      endocrine cells population were evaluated in jejunal biopsies from celiac
      children; findings were compared to active celiac patients on a challenge diet.
      Patients were divided as follows: Group A: 14 children with active untreated
      celiac disease; Group B: 7 celiac children on gluten challenge who had received
      diet therapy for the past 2 years; Group C: 8 normal control children. Jejunal
      biopsies were used for endocrine cell population measurement by
      immunocytochemistry, using a specific marker (chromogranin), and for prostanoid
      radioimmunological evaluation. The quantitative assessment of the endocrine cell
      population in Groups A and B revealed a significantly higher number of endocrine
      cells (20 +/- 11.5; 18.4 +/- 9.8 n. cell/visual field respectively) compared to
      Group C (8.44 +/- 2.3 n. cell/visual field) (p less than 0.05). In the jejunal
      extract the PGE2 content (341.8 +/- 82.3) ng/g) for Group A biopsies was
      significantly higher than that of Group C biopsies (93 +/- 23 ng/g) (p less than
      0.05. The PGE2 content (69.4 +/- +13.2 ng/g) for Group B did not show any
      statistically significant change. In contrast, TxB2 content in jejunal biopsies
      from all three groups was not significantly different.

PMID- 1974030
TI  - Pneumocystis carinii pneumonia in infants infected with the human
      immunodeficiency virus with more than 450 CD4 T lymphocytes per cubic millimeter.

PMID- 1974031
TI  - The X, Y, Z of head development.

PMID- 1974032
TI  - Adhesion receptors of the immune system.
AB  - The adhesive interactions of cells with other cells and with the extracellular
      matrix are crucial to all developmental processes, but have a central role in the
      functions of the immune system throughout life. Three families of cell-surface
      molecules regulate the migration of lymphocytes and the interactions of activated
      cells during immune responses.

PMID- 1974033
TI  - Arachidonic acid metabolites as mediators of somatostatin-induced increase of
      neuronal M-current.
AB  - The M-current (IM) is a time- and voltage-dependent K+ current that persists at
      slightly depolarized membrane potentials. IM is reduced by muscarinic cholinergic
      agonists and certain peptides, and is thought to be responsible in part for the
      slow and late slow excitatory postsynaptic potentials in sympathetic neurons.
      Recently, we reported that IM in hippocampal neurons was also augmented by
      somatostatin-14 and -28 suggesting that two different receptors reciprocally
      regulate one neuronal channel type. Muscarinic effects on IM may be mediated by
      various components of the phosphatidylinositol phosphate pathway. We now report
      the involvement of a different second messenger pathway, that generated by
      phospholipase A2, in the somatostatin-induced augmentation of IM in hippocampal
      cells. This pathway generates arachidonic acid from which leukotrienes can be
      produced by lipoxygenases. We find that the IM-augmenting effects of somatostatin
      are abolished by two substances that can inhibit phospholipase A2, quinacrine and
      4-bromophenacyl bromide, and that both arachidonic acid and leukotriene C4 mimic
      the effects of somatostatin-14 on hippocampal pyramidal neurons in vitro.
      Arachidonic and somatostatin effects are blocked by a lipoxygenase inhibitor,
      implicating an arachidonic acid metabolite, perhaps a leukotriene, in the
      somatostatin effect.

PMID- 1974034
TI  - Dual-component NMDA receptor currents at a single central synapse.
AB  - Present thinking about the way that the NMDA (N-methyl-D-aspartate) class of
      glutamate receptor operates at central synapses relies mainly on information
      obtained from single-channel and whole-cell recordings from cultured neurons
      stimulated by exogenous NMDA receptor agonists. The mechanisms that operate in
      the postsynaptic membrane of a normal neuron following release of the natural
      transmitter are far less clear. An important problem is that most normal neurons
      receive many excitatory synapses (10(3)-10(5) per cell) and these synapses are
      located on slender dendritic elements far away from the somatic recording site,
      making the study of discrete synaptic events difficult. Typically, when
      populations of synapses are activated, NMDA receptor-mediated synaptic potentials
      appear as slowly rising, long-lasting waves superimposed on faster, non-NMDA
      receptor potentials. Although believed to be critical for NMDA receptor function,
      this slow time-course would not be predicted from single-channel kinetics and its
      origin remains puzzling. We have now analysed the events occurring at the level
      of a single excitatory synapse using a simple, small, neuron--the cerebellar
      granule cell--which has an unusually simple glutamatergic input. By applying high
      resolution whole-cell recording techniques to these cells in situ, we were able
      to study the nature of elementary NMDA receptor-mediated synaptic currents.
      Contrary to expectations, the prominent currents are fast but are followed by
      slow ones. Both types of current are strongly voltage-dependent but differ subtly
      in this respect. Furthermore, the currents are absent unless glycine is provided.

PMID- 1974035
TI  - Mediation of Drosophila head development by gap-like segmentation genes.
AB  - The first phase of embryonic development in Drosophila consists of the
      elaboration and interpretation of maternally encoded information that specifies
      spatial pattern in the embryo. The product of the maternal gene bicoid (bcd) is
      thought to organize the anterior pattern of the embryo. Although the bcd
      transcript is localized at the anterior pole of the egg the bcd protein forms a
      stable concentration gradient through the anterior two thirds of the embryo. The
      graded distribution of bcd protein defines position along the anterior-posterior
      axis of the embryo through the spatially restricted activation of subordinate
      targets such as the gap gene hunchback (hb). In vitro manipulation of specific
      bcd protein binding sites has shown that the gradient of bcd protein can in
      principle define more than one discrete domain of spatially restricted gene
      activation in the head of the embryo, depending on the affinity of the available
      binding sites for the bcd protein. Genetic analysis has indicated the need for at
      least one additional zygotic segmentation gene to mediate bcd function in
      portions of the head that lie anterior to the hb domain. The missing gene
      activity is expected to be activated in response to higher levels of bcd protein
      than are required for hb activation. We report here that three previously
      identified zygotic genes buttonhead (btd), empty spiracles (ems) and
      orthodenticle (otd) may behave like gap genes that mediate bcd function in the
      embryonic head.

PMID- 1974036
TI  - The orthodenticle gene is regulated by bicoid and torso and specifies Drosophila
      head development.
AB  - In the Drosophila embryo, cell fate along the anterior-posterior axis is
      determined by maternally expressed genes. The activity of the bicoid (bcd) gene
      is required for the development of larval head and thoracic structures, and that
      of maternal torso (tor) for the development of the unsegmented region of the head
      (acron). In contrast to the case of thoracic and abdominal segmentation, the
      hierarchy of zygotically expressed genes controlling head development has not
      been clearly defined. The bcd protein, which is expressed in a gradient,
      activates zygotic expression of the gap gene hunchback (hb), but hb alone is not
      sufficient to specify head development. Driever et al. proposed that at least one
      other bcd-activated gene controls the development of head regions anterior to the
      hb domain. We report here that the homeobox gene orthodenticle (otd), which is
      involved in head development, could be such a gene. We also show that otd
      expression responds to the activity of the maternal tor gene at the anterior pole
      of the embryo.

PMID- 1974037
TI  - Channel kinetics determine the time course of NMDA receptor-mediated synaptic
      currents.
AB  - Synaptic release of glutamate results in a two component excitatory postsynaptic
      current (e.p.s.c.) at many vertebrate central synapses. Non-N-methyl-D-aspartate
      receptors mediate a component that has a rapid onset and decay while the
      component mediated by N-methyl-D-aspartate (NMDA) receptors has a slow rise-time
      and a decay of several hundred milliseconds, 100 times longer than the mean open
      time of NMDA channels. The slow decay of the NMDA-mediated e.p.s.c. could be due
      to residual glutamate in the synaptic cleft resulting in repeated binding and
      activation of NMDA receptors. However, in cultured hippocampal neurons, we find
      that the NMDA receptor antagonist D-2-amino-5-phosphonopentanoate has no effect
      on the slow e.p.s.c. when rapidly applied after activation of the synapse,
      suggesting that rebinding of glutamate does not occur. In addition, a brief pulse
      of glutamate to an outside-out membrane patch results in openings of NMDA
      channels that persist for hundreds of milliseconds, indicating that glutamate can
      remain bound for this period. These results imply that a brief pulse of glutamate
      in the synaptic cleft is sufficient to account for the slow e.p.s.c.

PMID- 1974038
TI  - [Cyclosporin (CyA) and H2 antagonists].
AB  - An experimental study on rats in order to discovery any possible interaction
      between Ciclosporin (CyA) and H2-receptor antagonists has been carried out. The
      results obtained demonstrated that the serum levels of CyA were higher in rats
      treated with CyA and Cimetidine or Ranitidine, but not Famotidine. It is probable
      that the increase of ciclosporinaemia is the consequence of an increased
      hepatotoxicity due to administration of Cya in association with Cimetidine or
      Ranitidine.

PMID- 1974039
TI  - Tyrosine hydroxylase immunoreactive interplexiform cells in the lamprey retina.
AB  - The distribution of tyrosine hydroxylase immunoreactivity was investigated in
      retinae of metamorphic, postmetamorphic and adult lampreys. Immunoreactive cell
      bodies were located mainly in the innermost part of the inner nuclear layer, with
      a few cells scattered throughout the inner plexiform layer. The processes of
      these neurons ran preferentially in the inner plexiform layer. Additionally,
      dense plexus of labelled processes were observed in the outer plexiform and
      nuclear layers. These findings suggest that most of the tyrosine hydroxylase
      immunoreactive cells in the lamprey retina are interplexiform cells.

PMID- 1974040
TI  - Effects of antagonists on N-methyl-D-aspartate response in acutely isolated
      nucleus tractus solitarii neurons of the rat.
AB  - The effect of antagonists on N-methyl-D-aspartate (NMDA)-induced response was
      investigated in isolated nucleus tractus solitarii (NTS) neurons freshly isolated
      from the rat using a conventional pathclamp technique. The NMDA-induced inward
      current consisted of an initial peak followed by a steady-state component. The
      competitive antagonists of NMDA receptor, D-2-amino-5-phosphonovalerate (APV), D
      2-amino-4-phosphonoheptanoate (APH) and 3-3(2-carboxypiperazine-4-yl)propyl-1
      phosphate (CPP), selectively suppressed the initial peak of NMDA-induced current
      more than the steady-state component at low concentrations. The non-competitive
      antagonists, MK-801, ketamine, Zn2+ and Mg2+, equally blocked both peak and
      steady-state components.

PMID- 1974041
TI  - Effect of typical and atypical neuroleptic treatment on protachykinin mRNA levels
      in the striatum of the rat.
AB  - A significant population of striatal neurons synthesize the tachykinin peptides
      substance P and neurokinin A. The synthesis of these neuropeptides is under tonic
      stimulation by dopaminergic neurotransmission. Since typical and atypical
      neuroleptic drugs display differential effects on the activity of dopaminergic
      neurons, we evaluated the effect of typical (haloperidol and prolixin) and
      atypical (molindone, thioridazine and chlozapine) chronic neuroleptic treatment
      on protachykinin mRNA levels in the medial aspect of the caudate-putamen by in
      situ hybridization histochemistry. Both typical and atypical neuroleptics
      decreased protachykinin mRNA levels by 22-40% relative to saline-injected
      controls. Clozapine failed to affect protachykinin mRNA levels. The data suggest
      the hypothesis that decreased striatal protachykinin mRNA levels may not be
      directly linked to development of extrapyramidal side effects.

PMID- 1974042
TI  - The CPN and depot injections.

PMID- 1974043
TI  - Mapping of the X-linked recessive retinitis pigmentosa gene. A review.
AB  - X-linked retinitis pigmentosa is caused by (a) mutation(s) on the X chromosome.
      One of the problems encountered in the genetic counselling of this disease is the
      identification of carrier females who appear ophthalmologically and
      electrodiagnostically normal. Despite normal testing these women are at risk of
      transmitting the XLRP gene to their children. Since the biochemical basis of XLRP
      is unknown, prenatal diagnosis and definitive carrier detection remain elusive.
      Existing methods of diagnosis and carrier detection are subject to limitations
      and are dependent on X-inactivation. The application of recombinant DNA probes to
      families with XLRP has provided a large number of genetic marker loci at the
      level of DNA. These markers are called restriction fragment length polymorphisms
      (RFLPs). By analysis of linkage relationships in affected kindreds, the XLRP
      gene(s) has (have) been localized to two subregions of the short arm of the X
      chromosome, Xp11 and Xp21. These findings suggest that there may be more than one
      retinitis pigmentosa gene on the X chromosome. Until further families are studied
      to clarify the localization(s) of XLRP, neither locus can be excluded if prenatal
      diagnosis and accurate carrier detection is to be established.

PMID- 1974044
TI  - Duchenne muscular dystrophy (DMD) gene cDNA 8 PstI and TaqI polymorphisms involve
      exon 51 of the HindIII map.

PMID- 1974045
TI  - Hypervariable individual-specific DNA band patterns revealed by a 22mer promoter
      specific oligonucleotide probe containing an SP1 site.

PMID- 1974047
TI  - [Effects of the treatment using synthetic LH-RH nasal spray in cryptorchism].
AB  - The effects of hormonal treatment with synthetic LH-RH (Kryptocur) applied as
      nasal spray at a dose of 1.2 mg daily over a period of 28 days were investigated
      on 62 undescended testes in 40 boys divided in two groups: below and above 6
      years. Only retained testes were treated. Complete descent was achieved primarily
      in 46.7%, but follow up examination 6 months after therapy showed relapse in 9%,
      so that percent was reduced to 39.7%. Therapy was more effective in patients with
      unilateral undescended testes aged below 6 years; however they showed relapse in
      33%. Bilateral undescended testes were more sensitive to the treatment (25%) in
      children aged over 6 years. In these patients we didn't observe relapse. No
      hormonal changes in FSH, LH and testosterone were observed before and after
      treatment, whether in basal or in pick after 25 micrograms i.v. of LHRH. 3 boys
      treated unsuccessfully showed low values of FSH after LHRH test at end of
      treatment. Treatment of cryptorchidism with intranasal synthetic LH-RH seems to
      be effective without side effects and painless. For this reason it may be used as
      attempt before surgery, particularly in boys aged below 6 years.

PMID- 1974046
TI  - PvuII and XhoI/EcoRV polymorphisms adjacent to the alpha A-crystallin (CRYA1)
      gene on human chromosome 21.

PMID- 1974048
TI  - Testing the efficacy of new neuroleptic drugs.

PMID- 1974049
TI  - Evaluating antidepressants and anxiolytics.

PMID- 1974050
TI  - Mechanism of elongation of primed DNA by DNA polymerase delta, proliferating cell
      nuclear antigen, and activator 1.
AB  - In the presence of a single-stranded-DNA-binding protein (SSB), the elongation of
      primed DNA templates by DNA polymerase delta (pol delta) is dependent on ATP and
      two protein factors, activator 1 (A1) and proliferating cell nuclear antigen
      (PCNA). We have examined the interaction of these proteins with (dA)4500.(dT)12
      18 by measuring their ability to form stable complexes with this DNA. In the
      presence of ATP, A1, PCNA, and pol delta formed a stable complex with DNA that
      could be isolated by gel filtration. Incubation of the isolated complex with dTTP
      resulted in the synthesis of poly(dT). While ATP was required for the formation
      of this complex, it was not required for the subsequent elongation of DNA. The
      temporal requirements for complex formation were determined. A1 was found to bind
      first, followed by the ATP-dependent addition of PCNA to the A1.DNA complex,
      while pol delta was added last. Each of these complexes could be isolated by gel
      filtration, indicating that they possessed a high degree of stability. The
      binding of PCNA to the A1-SSB-coated primed DNA occurred with adenosine 5'-[gamma
      thio]triphosphate as well as ATP. However, the binding of pol delta to the
      PCNA.A1-DNA complex was observed only when the latter complex was formed in the
      presence of ATP. The complete complex was formed after incubation at 37 degrees C
      for 2 min, whereas no complex was detected after incubation at 0 degree C. These
      results indicate that these proteins act in a manner analogous to the accessory
      proteins that play critical roles in the elongation reaction catalyzed by T4
      phage DNA polymerase and Escherichia coli DNA polymerase III.

PMID- 1974051
TI  - Structural and functional comparisons of the Drosophila virilis and Drosophila
      melanogaster rough genes.
AB  - We have isolated the homeobox gene rough (ro) from Drosophila virilis. Comparison
      of the predicted amino acid sequences of the D. melanogaster and D. virilis rough
      proteins reveals that domains of high conservation, including the homeodomain,
      are interspersed with highly diverged regions. Stretches of significant sequence
      conservation are also observed in the 5' promoter region and in the introns. The
      D. virilis rough gene rescues the rough mutant phenotype and is properly
      regulated when introduced into the D. melanogaster genome. Thus the rough protein
      as well as the cis-regulatory elements that ensure proper temporal and spatial
      regulation are functionally conserved between these Drosophila species.

PMID- 1974053
TI  - Implementation of the template model of vision.
AB  - Adopting principles learnt from insect vision we have constructed model of a
      general-purpose front-end visual system for motion detection that is designed to
      operate in parallel along each photoreceptor axis with only local connections.
      The model is also designed to assist electrophysiological analysis of visual
      processing because it puts the response to a moving scene into sets of template
      responses similar to the distribution of activity among different neurons. An
      earlier template model divided the visual image into the fields of adjacent
      receptors, measured as intensity or receptor modulation at small increments of
      time. As soon as we used this model with natural scenes, however, we found that
      we had to look at changes in intensity, not intensity itself. Running the new
      model also generated new insights into the effects of very fast motion, of
      blurring the image, and the value of lateral inhibition. We also experimented
      with ways of measuring the angular velocity of the image moving across the eye.
      The camera eye is moved at a known speed and the range to objects is calculated
      from the angular velocity of contrasts moving across the receptor array. The
      original template model is modified so that contrast is saturated in a new
      representation of the original image data. This reduces the 8-bit grey-scale
      image to a log, 3 = 1.6-bit image, which becomes the input to a look-up table of
      templates. The output consists of groups of responding templates in specific
      ratios that define the input features, and these ratios lead into types of
      invariance at a higher level of further logic. At any stage, there can be
      persistent parallel inputs from all earlier stages. This design would enable
      groups of templates to be tuned to different expected situations, such as
      different velocities, different directions and different types of edges.

PMID- 1974052
TI  - Opioids from immunocytes interact with receptors on sensory nerves to inhibit
      nociception in inflammation.
AB  - Exogenous opioids can produce localized opioid receptor-mediated antinociception
      in peripheral inflamed tissue. Previous studies show that activation of
      endogenous opioids by a cold water swim in rats with hind paw inflammation
      results in a similar local antinociceptive effect but suggest that pituitary
      adrenal opioid pools are not directly involved in producing this effect. Here we
      show increased amounts of opioid peptides in immune cells infiltrating the
      inflamed tissue. Furthermore, we demonstrate immunoreactive opioid receptors on
      peripheral terminals of sensory neurons. The local administration of antibodies
      against opioid peptides or receptors or systemic pretreatment with the
      immunosuppressant cyclosporine blocks cold water swim-induced antinociception.
      These findings suggest that antinociception in inflammation can be brought about
      by endogenous opioids from immune cells interacting with opioid receptors on
      peripheral sensory nerves.

PMID- 1974054
TI  - Neural network model of visual cortex for determining surface curvature from
      images of shaded surfaces.
AB  - The visual system can extract information about shape from the pattern of light
      and dark surface shading on an object. Very little is known about how this is
      accomplished. We have used a learning algorithm to construct a neural network
      model that computes the principal curvatures and orientation of elliptic
      paraboloids independently of the illumination direction. Our chief finding is
      that receptive fields developed by units of such model network are surprisingly
      similar to some found in the visual cortex. It appears that neurons that can make
      use of the continuous gradations of shading have receptive fields similar to
      those previously interpreted as dealing with contours (i.e. 'bar' detectors or
      'edge' detectors). This study illustrates the difficulty of deducing neuronal
      function within a network solely from receptive fields. It is also important to
      consider the pattern of connections a neuron makes with subsequent stages, which
      we call the 'projective field'.

PMID- 1974055
TI  - Architecture of chicken muscles: short-fibre patterns and their ontogeny.
AB  - Staining for motor endplates and chemical digestion of five major muscles of the
      domestic chicken shows that these confirm the short-fibre strap muscle paradigm.
      The individual fibres are spindle-shaped, terminating in gradually tapering ends.
      The motor endplates of the individual fibres align in cross-bands along the
      length of the fascicles. These bands are spaced much more tightly than are
      comparable bands in mammals; unlike the condition in mammals, many fibres are
      longer than twice the interband spacing. The spacings between bands differ by
      more than a factor of five along the length of each muscle. The proportions among
      bands remain relatively constant. These proportions are not affected by the
      degree of muscular contraction, nor do they change with ontogeny, suggesting that
      the arrangement is established before hatching.

PMID- 1974056
TI  - The dependence of human bone texture on life style.
AB  - Neutron diffraction has been used to determine the preferred orientation of the
      hydroxyapatite crystals at the lower front edge of the tibia. The bones are
      compared for two Neolithic Orkney tribes. At Isbister, a muscular tribe on a
      hilly site engaged in heavy uphill work, whereas a tribe at Quanterness lived on
      level ground. The two sets are contrasted with the texture of present-day
      amputations. Values of 16, 8 and 3 are found for an 'index of manoeuvrability'
      for the Isbister, Quanterness and modern ankles, respectively.

PMID- 1974057
TI  - ATP-sensitive K(+)-channel run-down is Mg2+ dependent.
AB  - ATP-sensitive K(+)-channel currents were recorded from isolated membrane patches
      and voltage-clamped CRI-G1 insulin-secreting cells. Internal Mg2+ ions inhibited
      ATP-K+ channels by a voltage-dependent block of the channel current and decrease
      of open-state probability. The run-down of ATP-K+ channel activity was also shown
      to be [Mg2+]i dependent, being almost abolished in Mg2(+)-free conditions.
      Substitution of Mn2+ for Mg2+ did not prevent run-down, nor did the presence of
      phosphate-donating nucleotides, a protease or phosphatase inhibitor or
      replacement of Cl- by gluconate.

PMID- 1974058
TI  - Kinetic analysis of the sodium gating current in the squid giant axon.
AB  - A critical study has been made of the characteristics of the kinetic components
      of the sodium gating current in the squid giant axon, of which not less than five
      can be resolved. In addition to the principal fast component Ig2, there are two
      components of appreciable size that relax at an intermediate rate, Ig3 alpha and
      Ig 3 beta. Ig3 alpha has a fast rise, and is present over the whole range of
      negative test potentials. Ig3 beta is absent below -40 mV, exhibits a delayed
      onset and disappears on inactivation of the sodium system. There are also two
      smaller components, Ig1 and Ig4, with very fast and much slower relaxation time
      constants, respectively.

PMID- 1974059
TI  - A series-parallel model of the voltage-gated sodium channel.
AB  - A series-parallel model of the kinetics of the voltage-gated sodium channel is
      described. It goes some way towards reconciling the time-courses of the gating
      and macroscopic sodium currents in the squid giant axon with the molecular
      structure of the channel.

PMID- 1974060
TI  - Local circuitry in the IMHV of the domestic chick (Gallus domesticus).
AB  - The responses to local stimulation have been recorded from neurons in the
      intermediate part of the medial hyperstriatum ventrale (IMHV) of the domestic
      chick, by using an in vitro slice preparation. When the slice is bathed in gassed
      Krebs' solution, a single stimulus evokes a short-lasting diphasic response. The
      first phase is negative and lasts some 3 ms, whereas the second, positive phase
      is often of lower amplitude and usually persists for about 15 ms. The first phase
      is little altered by perfusion with either Ca2(+)-free Krebs' solution or Krebs'
      solution containing a high concentration of Mg2+. In contrast, the second phase
      is abolished by these procedures. The post-synaptic phase is positive when it is
      recorded anywhere between 0.1-1.25 mm from the stimulated point; however, in the
      immediate vicinity (0.0-0.1 mm) of the stimulating electrodes, the post-synaptic
      response is strongly negative. A pair of stimuli has to be separated by at least
      10 s to guarantee complete recovery of excitability of the post-synaptic
      response. The recovery curve for this response shows a refractory period of some
      5 ms, a peak of excitability at an interval of about 20 ms, and then a sharp
      trough of relative inexcitability at about 200 ms. The post-synaptic response is
      considerably reduced in magnitude and duration by the addition of AP-5 to the
      perfusion fluid; the remaining post-synaptic response is completely abolished by
      kynurenic acid. The addition of bicuculline methiodide in concentrations of at
      least 1 x 10(-6) M increases both the magnitude and duration of the second,
      positive phase of the response to single stimuli. This extended positive response
      (which may last from 500-800 ms) is abolished by perfusion with bicuculline
      dissolved in Ca2(+)-free Krebs' solution. For the entire duration of the extended
      post-synaptic positive response produced by bicuculline, the irregular discharge
      of single neurons can be recorded. Like the post-synaptic positive response in
      Krebs' solution, the much larger response produced by bicuculline shows a very
      localized negativity beneath the stimulating electrodes and displays an almost
      identical time-course for the recovery of excitability following a single
      stimulus. The bicuculline induced positive response is also considerably reduced
      by the presence of AP-5; the addition of kynurenic acid abolishes the remaining
      post-synaptic response completely. A post-synaptic response, similar to that
      produced under bicuculline, can be produced by the addition of a maximally
      effective dose of d-tubocurarine.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1974061
TI  - Connections of the IMHV in the domestic chick Gallus domesticus.
AB  - The responses to single electrical stimuli have been recorded from neurons in the
      brains of domestic chicks, by using an in vitro preparation consisting of a
      coronal slice taken from the forebrain. All slices were cut so that they
      contained the intermediate part of the medial hyperstriatum ventrale (IMHV). When
      such a slice is bathed in standard Krebs' solution there is no evidence that the
      excitation produced by a single stimulus can be transmitted more than 1 mm either
      towards or away from the IMHV. The addition of bicuculline methiodide (more than
      3 x 10(-6) M) to Krebs' solution allows the excitation produced by a single
      stimulus to spread in all directions throughout the dorsal half of a coronal
      slice. At points remote (more than 1.5 mm) from the stimulated point, the
      magnitude of the spreading wave of excitation bears an all-or-nothing relation to
      the strength of stimulus used to excite it. This wave of excitation spreads from
      the excited point in all directions without attenuation at 0.9 +/- 0.017 (s.d.) m
      s-1 and consists of a prolonged burst of activity of the invaded neurons. The
      properties of coronal slices described above are also true of brain slices cut in
      a parasagittal plane. The spreading response to a single stimulus given in the
      presence of bicuculline, can be reduced in magnitude by the addition of AP-5 but
      it still spreads throughout the dorsal part of the slice at the same velocity.
      The response can be eliminated by the addition of kynurenic acid. The addition of
      curare to the bathing medium produces similar responses that spread in a similar
      fashion to those seen under bicuculline. These results suggest that the dorsal
      part of the forebrain of the domestic chick (in fact, the part derived from the
      embryological alar plate) contains a network of reciprocally connected local
      circuits. Transmission throughout the network is normally prevented by active
      inhibition.

PMID- 1974062
TI  - Interpretation of agonist affinity estimations: the question of distributed
      receptor states.
AB  - In the receptor-transducer model of pharmacological agonism, rejection of the
      traditional assumption that receptor molecules are in vast excess of transducer
      molecules permits the receptors to become distributed among unbound, bound and
      complexed states. Under these conditions, agonist affinities are liable to be
      overestimated when the method of irreversible receptor antagonism is used.
      Graphical tests have been developed to detect distribution, and these were
      applied to experimental data from the interaction between 5-HT and
      phenoxybenzamine on aortic tissue. Significant receptor distribution was not
      detected by the method. However, in the model it was assumed that there was a
      linear relation between the concentration of ternary complex and pharmacological
      effect. If this relation was replaced with a saturable one the effect of receptor
      distribution would be masked. The implications for pharmacologists and medicinal
      chemists are discussed.

PMID- 1974063
TI  - Energy absorption from ocean waves: a free ride for cetaceans.
AB  - Flukes of cetaceans are capable of absorbing energy from ocean waves for
      propulsion. The extent of this energy absorption is demonstrated by considering
      the flukes of an immature fin whale, Balaenoptera physalus. In a fully developed
      seaway corresponding to a wind speed of 20 knots (around Beaufort force 5) and at
      a low swimming speed, of 2.5 m s-1, this whale was able to absorb up to 25% of
      its required propulsive power in head seas and 33% of propulsive power in
      following seas. Consequences of wave-energy absorption for energetics of cetacean
      migrations are discussed.

PMID- 1974065
TI  - The role of D1 and D2 receptors in dopamine agonist-induced modulation of
      affective defense behavior in the cat.
AB  - The role of D1 and D2 dopamine (DA) receptor subtypes in mediating DAergic
      modulation of affective defense behavior in the cat has been investigated in the
      present study. Feline affective defense, characterized mainly by autonomic
      arousal, ear retraction, hissing and paw striking, was elicited by electrical
      stimulation of the ventromedial hypothalamus. Following the establishment of a
      stable threshold current for eliciting the hissing response of the behavior, the
      effect of systemic (IP) administration of various DAergic agonists and
      antagonists on the hissing threshold was determined. The injection of the
      nonselective DA agonist apomorphine (1.0, 0.3 and 0.1 mg/kg) facilitated hissing
      in a dose-related manner. This effect was mimicked by the D-2 selective agonist
      LY 171555 (0.1, 0.03 and 0.01 mg/kg) but not by the D1-selective agonist SKF
      38393 (1.0, 5.0 and 10.0 mg/kg), and was blocked by the nonselective and the D2
      selective antagonists haloperidol (0.1 and 0.5 mg/kg) and spiperone (0.2 mg/kg),
      respectively. The D1-selective antagonist SCH 23390 blocked apomorphine-induced
      facilitation only at a high dose (0.5 mg/kg). In addition, the injection of
      haloperidol (1.0 mg/kg), spiperone (0.2 mg/kg) or SCH 23390 (0.1 mg/kg) alone
      inhibited the behavior. It was therefore concluded that DAergic facilitation of
      affective defense behavior is mainly mediated by the D2 receptors, but that
      activation of the D1 receptors may play a "permissive" role. The interaction
      between the D1 and D2 receptors in mediating this facilitation and the behavioral
      specificity of the effect are discussed.

PMID- 1974064
TI  - Chronic cocaine treatment impairs the regulation of synaptosomal 3H-DA release by
      D2 autoreceptors.
AB  - The effect of repeated administration of cocaine on presynaptic D2 autoreceptor
      sensitivity in synaptosomes was studied. In rats treated chronically with saline,
      the dopamine D2 agonist 2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin (N
      0437) caused a significant inhibition of the Ca2(+)-evoked 3H-DA release from
      synaptosomes prepared from the nucleus accumbens and from the striatum; this
      effect was blocked by the D2 antagonist sulpiride. However, chronic cocaine
      pretreatment abolished the effect of N-0437 in both areas, suggesting a
      subsensitivity of release-modulating terminal DA autoreceptors. Subsensitive DA
      autoreceptors would enhance stimulated DA release from mesolimbic and
      nigrostriatal terminals and may play a role in the behavioral sensitization
      observed in this paradigm.

PMID- 1974066
TI  - The role of dopamine in the effects of pentazocine and tripelennamine.
AB  - CNS dopamine has been suggested as a mediator in the effects of many drugs of
      abuse. The present study was conducted to assess the potential dopaminergic
      activity of pentazocine and tripelennamine combinations (T's and Blues). The
      effects of pentazocine and tripelennamine, administered alone and in combination
      with several dopaminergic drugs, on milk drinking were assessed in the rat. Both
      the opioid and antihistamine were tested in combination with apomorphine and
      haloperidol. Pentazocine was also tested in combination with the D1- and D2
      receptor selective antagonists SCH 23390 and raclopride, and with the D2-receptor
      agonist quinpirole. Tripelennamine was additionally tested in combination with
      methamphetamine. Haloperidol and quinpirole pretreatment produced leftward shifts
      in the pentazocine dose-effect curve while raclopride and SCH 23390 shifted the
      opioid curve to the right. Doses of apomorphine shifted tripelennamine's dose
      effect curve to the left, tripelennamine enhanced the effects of methamphetamine,
      but haloperidol did not alter the antihistamine's effects. These data suggest
      dopaminergic involvement in the effects of the opioid and antihistamine.

PMID- 1974067
TI  - Opioid agonists/antagonists in morphine-tolerant squirrel monkeys.
AB  - The mu-opioid agonist morphine, the opioid antagonist naloxone and the isomers of
      the mixed action opioids, cyclazocine, n-allylnormetazocine, and pentazocine were
      examined in squirrel monkeys responding under a fixed-ratio 30 schedule of food
      presentation. Dose-effect curves for all drugs were obtained prior to, during,
      and following a chronic regimen in which monkeys received 6 mg/kg/day of
      morphine. When compared to the dose-effect curves obtained prior to the chronic
      regimen, the morphine dose-effect curve obtained during the chronic regimen was
      shifted to the right 0.5-1.0 log unit, whereas the naloxone dose-effect curve
      shifted over 3 log units to the left. No changes were observed between the
      prechronic and chronic dose-effect curves for (+)-cyclazocine, (+)-n
      allylnormetazocine, and (+)- or (-)-pentazocine. The (-) isomers of n
      allylnormetazocine and cyclazocine shifted 0.6-1.7 log units to the left. These
      results suggest that the (-) isomers of cyclazocine and n-allylnormetazocine have
      mu antagonist properties which are revealed during chronic morphine
      administration.

PMID- 1974068
TI  - Selectivity for omega-receptor subtypes as a strategy for the development of
      anxiolytic drugs.
AB  - The names omega 1-, omega 2-, and omega 3-receptor subtypes have recently been
      proposed to replace the nomenclature of BZ1, BZ2 and BZp receptors in order to
      avoid a nomenclature exclusively linked to the benzodiazepine (BZ) structure or
      to a regional localization. The multiplicity of pharmacological actions of
      currently available anxiolytics may be due to their lack of selectivity for omega
      receptor subtypes. The idea that a receptor-subtype selective drug will offer a
      more specific therapeutic profile is widely accepted. In the field of
      preferential anxiolytic or hypnotic drugs, imidazopyridines represent a new
      chemical and therapeutic class possessing selectivity for omega-receptor
      subtypes. Of these, alpidem (6-chloro-2-(4-chloro-phenyl)-N,N-dipropylimid
      azo[1,2-a] pyridine-3-acetamide) behaves preferentially as an anxiolytic drug in
      both animal models and man. Receptor-binding studies using alpidem either as a
      displacer or as a radioligand indicate that the compound has a high affinity for
      omega 1- and for omega 3- but not for omega 2-receptors. In the human brain, the
      binding of [3H]-alpidem to omega 1- and omega 3-receptors occurs with a Kd of
      1.67 nM and 0.33 nM respectively. The binding of [3H]-alpidem to omega 1
      receptors in the rat cerebral cortex with a Kd of 1.5 nM is enhanced by GABA, and
      in contrast to anxiolytics of the benzodiazepine type, is unaffected by chloride
      ions and pentobarbital. In conclusion, the affinity of alpidem for the omega 1
      receptor is allosterically influenced by the activation of the GABAA receptor but
      not by other components of the same receptor complex.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1974069
TI  - Pharmacological and behavioral profile of alpidem as an anxiolytic.
AB  - Pharmacological and behavioral studies in mice and rats have shown that the
      imidazopyridine alpidem possesses anxiolytic activity with a profile which is
      substantially different from that of benzodiazepines. Thus, in mice, alpidem
      inhibited marble-burying behavior and enhanced feeding under stressful
      conditions, as did benzodiazepines; in contrast to these drugs, however, alpidem
      was inactive against shock-induced fighting and shock-suppressed exploration. In
      rats, alpidem exerted anticonflict activity in the punished drinking test, but
      failed to antagonize punishment-induced inhibition of operant behavior. Moreover,
      in rats trained to discriminate chlordiazepoxide from saline, alpidem did not
      produce a benzodiazepine-like interoceptive stimulus. Alpidem also produced
      anticonvulsant effects in a variety of tests sensitive to benzodiazepines.
      However, the order of potencies against convulsions induced by different
      convulsive agents was different from that of the benzodiazepines. Alpidem
      decreased motor performance in the rotarod test and only produced a deficit in
      muscle strength at doses which were more than 20 times higher than the doses
      active in anxiolytic tests. Moreover, alpidem did not interfere with the
      acquisition of conditioned fear, except at very high doses, indicating a weak
      potential to impair memory. The effects of alpidem were antagonized by
      flumazenil, indicating that central omega receptors are involved in the action of
      this drug. The weak sedative effects of alpidem may be attributed to its low
      intrinsic activity, as demonstrated by its low efficacy in increasing latency to
      isoniazid-induced convulsions.

PMID- 1974070
TI  - Effects of single doses of alpidem, lorazepam, and placebo on memory and
      attention in healthy young and elderly volunteers.
AB  - The aim of the present study was to compare the effects of alpidem, a new
      imidazopyridine derivative with benzodiazepine-like anxiolytic effects, with
      those of lorazepam and placebo on memory and attention in two age groups of
      healthy volunteers. The study design was that of a randomized double-blind
      crossover trial with 12 young (18-30 years old) and 12 elderly (65-80) subjects.
      At weekly intervals, each subject was administered single oral doses of 25 mg
      alpidem, 50 mg alpidem, 1 mg lorazepam, and placebo in a randomized sequence.
      Computerized memory and attention tests were performed 90 minutes before and 320
      minutes after drug administration. Lorazepam and alpidem 50 mg produced memory
      impairments: for verbal memory tests the difference against placebo was highly
      significant for both drugs, while for visual memory this impairment was
      significant for lorazepam only. No memory effects were seen with 25 mg alpidem.
      There were no significant drug effects on attention, suggesting a specific
      amnestic effect not explained by general sedation. Performance of the elderly
      subjects was much lower than that of the younger ones in both memory and
      attention tasks. It was not possible to observe any interaction effects between
      drug and age.

PMID- 1974071
TI  - Studies with alpidem in normal volunteers and anxious patients.
AB  - Alpidem, an imidazo-pyridine compound, has been evaluated as an anxiolytic in
      comparison with placebo and lorazepam. In the first of our normal volunteer
      studies, we compared single doses of alpidem, 25, 50 and 100 mg with lorazepam 2
      mg and placebo on a range of cognitive, psychomotor and EEG variables. Lorazepam
      and the highest (100 mg) dose of alpidem impaired performance on a range of
      psychomotor tasks, the effects of the benzodiazepine being more severe and more
      prolonged. No impairment of performance was observed with the 25 and 50 mg doses.
      In the second study, the focus was on memory functions. Lorazepam, 2 mg, caused
      anterograde amnesia which was most apparent 1 h post-drug but persisted until 4
      h: sedation was marked. By contrast, single doses (25, 50 mg) of alpidem had
      little effect on either memory or alertness. The third study compared the effects
      of alpidem (25, 50 mg) and lorazepam (1 mg) with placebo, each given twice-daily
      for 8 days to normal volunteers. On the final day, a test dose of ethanol was
      given. Lorazepam impaired many tests of cognitive and psychomotor function, and
      this impairment was enhanced by ethanol. By contrast, alpidem produced less
      impairment with less interaction with alcohol. In a fourth, clinical, study, 24
      patients with a DSM III primary diagnosis of generalised anxiety disorder were
      treated, under double blind conditions, with doses adjusted according to clinical
      need of either alpidem 25-150 mg daily or lorazepam 1-6 mg daily.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1974072
TI  - Alpidem and psychological performance in elderly subjects.
AB  - With increasing age there is a concurrent increase in the side effects following
      psychotropic medication. The necessity of measuring the magnitude of the extent
      of the side effects using a properly constructed psychometric test battery is
      illustrated with reference to a dose ranging study compared to acute dose effects
      of 25, 50 and 100 mg alpidem in a population of elderly volunteers. The study was
      both placebo and verum (lorazepam 2 mg) controlled and the treatments were
      administered according to a crossover design with each subject acting as their
      own control. The effects of the verum were evident on all the tests and under
      these conditions there was no effect on psychological differences following doses
      of 25 and 50 mg alpidem. There was an initial deterioration one hour after dosing
      following 100 mg alpidem which was readily attenuated by three hours. No
      differences with any of the doses of alpidem were able to be detected at any
      other time point even though the verum continued to show the sensitivity of the
      battery to tests to sedative amnestic sensori-motor and information processing
      activities.

PMID- 1974073
TI  - On the therapeutic action of alpidem in anxiety disorders: an overview of the
      European data.
AB  - This review analyzes the available data on the therapeutic activity of alpidem in
      various anxiety syndromes. Up to now, 17 studies have been completed in Europe,
      dealing with a total population of more than 1500 patients suffering from either
      chronic (n = 987) or situational anxiety (n = 400). In a series of five placebo
      controlled double-blind studies in situations of stress-induced anxiety
      (gastroscopy, minor surgery, cardiac catheterization), the therapeutic efficacy
      of alpidem was evident in 53% of the patients and significantly (P less than
      0.001) superior to that of placebo (30%). In more than 400 patients suffering
      from generalized anxiety or adjustment disorders with anxious mood, six double
      blind studies run against placebo or reference drug over a period of two to three
      weeks indicated an anxiolytic effect superior (P less than 0.01) to that of
      placebo and comparable to that of reference drugs (DZ, LZP, CZP). A long-term (6
      12 months) open-label study conducted on a population of more than 300 patients
      suffering from chronic anxiety indicated that no tachyphylaxis occurs during
      prolonged treatment and that following abrupt drug discontinuation no withdrawal
      or rebound phenomena are observed. Globally, alpidem appears to be well tolerated
      with a minimum of dose-related, sedative effects (6-7% of the cases) and no
      effects on memory or cognitive functions. Four studies conducted specifically in
      an elderly population (n = 191) indicate that the elderly patients do not show an
      increased sensitivity to alpidem. On the contrary, as in adults, the anxiolytic
      effect was not accompanied by a reduction in performance or in cognitive
      functions nor by withdrawal reactions when treatment was discontinued.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1974074
TI  - The response of the cerebral hemisphere of the rat to injury. I. The mature rat.

PMID- 1974075
TI  - The response of the cerebral hemisphere of the rat to injury. II. The neonatal
      rat.

PMID- 1974076
TI  - [Schizophrenia in adolescents--a follow-up study].
AB  - The article presents the results of a catamnesis of patients (both female and
      male) who had been in-patients for the first time between 1972 and 1978 because
      of signs and symptoms of schizophrenic diseases and who were between 14 and 18
      years of age. For 51 patients data were available on long-term follow-up for at
      least 5 years. Compared with the available catamneses of adults of the
      'seventies, the proportion of chronic cases is greater among the adolescents. The
      patterns of signs and symptoms do not differ significantly from each other. In
      addition, it was found that the treatment chain had many weak links despite an
      improvement due to the setting up of child psychiatry and juvenile psychiatric
      wards; in other words, treatment was mostly discontinuous and not adapted to long
      term course of the disease.

PMID- 1974077
TI  - The status of expectancy-arousal theory: comparative credibility of systematic
      desensitization and rational-emotive therapy in the treatment of anxiety about
      study.
AB  - 96 university students were asked to imagine that they were suffering from study
      anxiety to the point of wishing to receive help with the problem. They were then
      asked to read a booklet detailing either (a) the rationale for systematic
      desensitization or Rational-Emotive Therapy and (b) told that counselling lasted
      for 5 or 15 weeks. They then assessed the credibility of the therapy using
      Borkovec's credibility rating method. Meta-analysis has shown that systematic
      desensitization has superior outcomes when compared to other treatments, but this
      could be attributed to the different expectations of benefit that the therapies
      arouse. This notion has been called the expectancy-arousal hypothesis. Results
      from the present experiment did not support Shapiro's 1981 findings that
      systematic desensitization was more credible than Rational-Emotive Therapy, which
      disconfirms the expectancy-arousal hypothesis, but the basis for this remains
      unclear.

PMID- 1974078
TI  - Psychopharmacologic treatment issues.

PMID- 1974079
TI  - Biological mechanisms of schizophrenia: an update.

PMID- 1974080
TI  - Influence of somatostatin and epidermal growth factor (EGF) on the proliferation
      of thyroid follicular cells in organ culture.
AB  - The aim of the present study has been to examine the effects of various
      concentrations of somatostatin (SS), epidermal growth factor (EGF), as well as of
      interactions among SS, EGF and thyrotropin (TSH) in their influence upon the
      mitotic activity of thyroid follicular cells (TFC) in organ culture. The
      stathmokinetic method was employed. It was shown that: (1) SS, at the
      concentration of 10(-7) M, suppressed the mitogenic effect of TSH, as well as of
      TSH and EGF employed together, on TFC; (2) EGF, at the concentration of 10 and
      100 ng/ml, increased the mean mitotic activity rate of TFC; (3) TSH and EGF
      revealed an additive action on TFC proliferation. The obtained results evidently
      suggest an antiproliferative effect of SS and mitogenic action of EGF on TFC in
      organ culture.

PMID- 1974082
TI  - Cases of the day. Ultrasound. Takayasu arteritis.

PMID- 1974081
TI  - The immunostaining for the hypothalamic vasoactive intestinal peptide, but not
      for beta-endorphin, dynorphin-A or methionine-enkephalin, is affected by the
      glucocorticoid milieu in the rat: correlation with the prolactin secretion.
AB  - Effects of the glucocorticoid milieu on the basal and ether stress-induced
      prolactin (PRL) release and on the immunostaining for hypothalamic vasoactive
      intestinal peptide (VIP), beta-endorphin (beta-EP), dynorphin-A (DYN-A) and
      methionine-enkephalin (Met-ENK), were examined in separate groups of male rats.
      After colchicine treatment in intact rats, VIP-containing cell bodies were
      observed only in the suprachiasmatic nucleus (SCN). Adrenalectomy (ADX),
      performed 7 days previously, resulted in the additional appearance of VIP
      immunoreactive neurons in the parvocellular subdivision of the paraventricular
      nucleus (PVN), as well as in significantly higher basal and stressed PRL levels
      than intact values. Treatment of intact rats with a high dose (500 micrograms/kg
      body weight (s.c.) daily for 7 days) of dexamethasone (DEX), but not with a low
      dose (50 micrograms/kg) of DEX, significantly reduced both the basal and stressed
      PRL release. Administration of either the low or high dose of DEX to ADX rats
      prevented the appearance of the PVN-VIP neurons. In addition, the ADX-induced
      high basal and stressed PRL levels were restored to intact values by the low dose
      of DEX, and completely suppressed by the high dose of DEX. The staining of SCN
      VIP-, beta-EP-, DYN-A or Met-ENK neurons was not affected by any treatment
      employed in this study. These results suggest that the appearance of PVN-VIP
      immunostaining in ADX rats may, at least in part, be responsible for the enhanced
      PRL secretion observed in this group. However, SCN-VIP-, beta-EP-, DYN-A- or Met
      ENK neurons do not seem to play a pivotal role in the glucocorticoid regulation
      of PRL secretion.

PMID- 1974083
TI  - [The effect of Ridaura on cardiac function in patients with rheumatoid arthritis
      (based on echocardiographic data)].
AB  - The method of echocardiography was used to study the effect of ridaura on the
      functional state of the heart in patients with rheumatoid arthritis (RA)
      depending on the duration of therapy and its efficacy. A total of 28 patients
      with RA were examined in the dynamics of therapy. The favourable effect of
      ridaura on the size of the left ventricle of the heart and its contractile
      function with the general positive effect of therapy was revealed. A decrease in
      the size of the left ventricle began 6 months after treatment with ridaura and
      continued up to the end of the first year, the contractile function considerably
      rose after two years of treatment. In 1/3 of the patients side effects developed;
      they manifested themselves in deterioration of the indices of hemodynamics. The
      unfavourable effect of ridaurotherapy on the myocardium had a latent course and
      was reversible.

PMID- 1974084
TI  - AIDS-related infections.

PMID- 1974085
TI  - Murine developmental control genes.
AB  - Various strategies have been used to isolate genes that participate in the
      regulation of mouse development. Gene families that have been identified on the
      basis of their homology to motifs within Drosophila control genes or human
      transcription factor genes, namely homeobox (Hox), paired-box (Pax), and POU
      genes, can be compared with respect to gene organization, structure, and
      expression patterns. The functions of these genes can be analyzed molecularly in
      vitro and in vivo with the use of available mouse mutants or transgenic mice. In
      addition, it has been possible to generate gain- or loss-of-function mutations by
      random or targeted introduction of transgenes. Models derived from these studies
      can reveal the successive steps of developmental control on a genetic level.

PMID- 1974086
TI  - [Neurobiology and eating behavior].

PMID- 1974087
TI  - Regulation of G protein-coupled receptors by agonist-dependent phosphorylation.

PMID- 1974088
TI  - Observations with norcuron (pharmaceutical works of Gedeon Richter, Budapest,
      Hungary) injection.
AB  - Vecuronium bromide (Norcuron) has been used as an intubation and surgical muscle
      relaxant besides the use of different types of anaesthesia in the course of 230
      gynaecological operations. With a single or repeated drug dose complete muscular
      relaxation could be assured during operation of 25-60-minute duration. In general
      the clinical muscle relaxant action lasted for about 30 minutes. Norcuron allowed
      to perform intubation within 40-120 sec. The drug could be combined with
      anaesthetics without risk. Cardiovascular unwanted effects or other after-effects
      did not occur. According to the author-s opinion, as a neuromuscular blocker of a
      short to medium duration of action, Norcuron is a long-needed drug in Hungarain
      anaesthesiological practice.

PMID- 1974089
TI  - Low incidence of HTLV infections in random blood donors with indeterminate
      western blot patterns.
AB  - Peripheral blood mononuclear cells (PBMCs) were recovered from platelet units of
      61 blood donors who were HTLV-I positive and 3 blood donors who were HTLV-I
      negative on enzyme-linked immunosorbent assay (ELISA). Western blot analyses were
      performed on the sera and DNA was prepared from the PBMCs and analyzed by the
      polymerase chain reaction (PCR). Of the 61 repeatably reactive samples, 2 were
      positive, 26 were negative, and 33 were interpreted as indeterminate on Western
      blot. HTLV-II sequences were detected by PCR in one of the Western blot-positive
      samples, as well as in one Western blot-indeterminate sample that showed
      reactivity to p24 only. HTLV-I sequences were detected in the second Western blot
      positive sample. HTLV sequences were not detected in the remaining samples, which
      suggested that the majority of individuals with indeterminate results on Western
      blots that used one set of commercially available reagents are not infected with
      HTLV. It is demonstrated in this study that PCR can be used not only to resolve
      the infection status of individuals with indeterminate Western blots but also to
      distinguish between HTLV-I and HTLV-II.

PMID- 1974090
TI  - Translumbar inferior vena cava catheters: safety and efficacy in peripheral blood
      stem cell transplantation.
AB  - Most patients who need peripheral blood stem cell transplantation do not have
      peripheral venous access that would allow apheresis for stem cell collection.
      Subclavian apheresis catheters have an unacceptably high incidence of thrombosis
      related access failure. A technique has been developed for translumbar placement
      of permanent, subcutaneously tunneled, silicone rubber apheresis catheters into
      the inferior vena cava, and 40 of these catheters have been placed in 36 patients
      for stem cell collection. Twenty-six catheters have been left in place for venous
      access during the transplantation procedure. These catheters had a very low rate
      (2.3%) of apheresis-related related complications. Access failure was attributed
      to thrombosis in 10 catheters (25%) and to mechanical complications in another 9
      (22%), but access was regained in all but 4 of these cases. The catheters
      functioned well as venous access devices during transplantation, only rarely
      developing complications during that time. Venograms performed at the time of
      removal of 16 catheters showed no case of caval occlusion. A residual fibrin
      sheath was found around 14 catheters. There was no clinical or computed
      tomographic scan evidence of bleeding after placement or removal of the
      catheters. Percutaneously placed, translumbar inferior vena cava apheresis
      catheters provide a safe and effective route for the collection of peripheral
      blood stem cells for transplantation, and they can be left in place for venous
      access during transplantation.

PMID- 1974091
TI  - The application of restriction fragment length polymorphism mapping to parentage
      testing.

PMID- 1974092
TI  - Phenotype modulation in primary cultures of rat aortic smooth muscle cells.
      Effects of drugs that interfere with the functions of the vacuolar system and the
      cytoskeleton.
AB  - The transition of adult rat aortic smooth muscle cells from a contractile to a
      synthetic phenotype during the first week of primary culture on a substrate of
      fibronectin in serum-free medium was studied by light and electron microscopy.
      The weak base chloroquine and the carboxylic ionophore monensin were both found
      to inhibit the spreading of the cells and the accompanying changes in cellular
      fine structure. The exchange of myofilament bundles for a prominent rough
      endoplasmic reticulum and Golgi complex was delayed and vacuoles filled with
      incompetely degraded material accumulated in the cytoplasm. The microtubule
      disruptive drugs colchicine and nocodazole likewise opposed the spreading and
      fine structural reorganization of the cells. Most typically, the Golgi stacks
      were small and widely dispersed. In addition, vacuoles of the type mentioned
      above increased in number. On the other hand, there was surprisingly little
      effect of cytochalasin B, a drug that is supposed to interfere with the assembly
      of actin filaments. The observations suggest that the phenotypic modulation of
      arterial smooth muscle cells is dependent on: (a) lysosomal degradation of
      discarded cellular constituents, (b) active vesicular transport along the
      exocytic pathway to provide the expanding cell surface with new membrane, and (c)
      a normal microtubular cytoskeleton to ensure the establishment of a new and
      functionally efficient intracellular organization.

PMID- 1974093
TI  - Expression of ras p21 protein by thymoma.
AB  - Histopathological examination of thymomas often fails to predict their malignant
      potential because the morphology of invasive or metastatic thymomas does not
      differ significantly from that of benign, encapsulated thymomas. In order to find
      a marker of aggressiveness in thymomas, 21 cases (9 non-invasive, 8 invasive and
      4 metastatic thymomas) were examined for expression of the ras oncogene product
      p21 by immunohistochemistry and immunoblot analysis. Immunohistochemical study,
      using a serially diluted monoclonal antibody, NCC-RAS-001, demonstrated that
      neoplastic thymoma cells generally contained more p21 than normal thymic
      epithelial cells. Immunoblot analysis using another monoclonal antibody (NCC-RAS
      004) also confirmed the increased concentration of p21 in all but one of the
      thymomas by comparison with normal thymic tissue. One metastatic thymoma did not
      have a band of p21 recognized by NCC-RAS-004 and was believed to have a deletion
      of the epitope recognized by this antibody. In addition, another metastatic
      thymoma showed abnormal electrophoretic mobility of p21. The increased amount of
      p21 in thymomas suggests that this protein has a role in the oncogenesis or
      progression of thymoma. The high incidence of a p21 molecular abnormality in
      metastatic thymomas indicates that the abnormality of this protein could be used
      as a possible marker of aggressive behavior.

PMID- 1974094
TI  - Effects of extra- and intracellular calcium concentration on DNA replication,
      lateral growth, and differentiation of human epidermal cells in culture.
AB  - Variation in the extra- and intra-cellular concentration of calcium ([Ca]e and
      [Ca]i) affected the 3H-thymidine labeling pattern of sorted S-phase cells in
      human epidermal cultures. A lowering of [Ca]e resulted in retarded lateral growth
      but, unless [Ca]e was extremely low, caused an increase in the proportion of
      strongly labelled (rapidly cycling) S-phase cells. An increased desquamation of
      superficial cells due to a reduced cellular cohesiveness was also observed in low
      calcium medium. Thus, a lowering of [Ca]e might stimulate the proliferation of a
      pool of cycling cells destined for rapid terminal differentiation and tissue
      regeneration, whereas proliferation destined for lateral growth is inhibited.
      Attempts to decrease the [Ca]i with the calcium chelator quin-2 at low [Ca]e
      seemed to elevate the proportion of strongly labelled S-phase cells, whereas an
      increased [Ca]i obtained with the ionophore A23187 caused a dramatic decrease in
      the proportion of S-phase cells that showed strong 3H-thymidine incorporation.
      This implies that variation in both [Ca]i and [Ca]e may play a role in the
      regulation of proliferation and differentiation, in keratinocytes.

PMID- 1974096
TI  - Inhibition of cellular autophagy in kidney tubular cells stimulated to grow by
      unilateral nephrectomy.
AB  - Cytoplasmic growth (hypertrophy) presupposes a positive metabolic balance brought
      about by increased anabolic and/or decreased catabolic processes. Degradation of
      cytoplasmic components takes place in autophagic vacuoles (AVs) whose volume
      fraction may be taken as a measure of the relative rate of degradation of
      cytoplasmic components. Male adult Sprague-Dawley rats (n = 80) were unilaterally
      nephrectomized (n = 40) or sham-operated (n = 40) and were killed 3.5-57.5 h p.o.
      The volume density of AVs in parenchymal cells of renal cortical convoluted
      tubules was determined morphometrically by systematic evaluation of large test
      fields in the electron microscope. During compensatory renal growth, the volume
      densities of autophagic vacuoles were reduced at day 0 (3.5-8 h p.o.), day 1
      (20.5-33.5 h p.o.) and day 2 (44.5-57.5 h p.o.) by 49% (p less than 0.01), 43% (p
      less than 0.05), and 19% (n.s.), respectively, when compared with sham-operated
      controls. No decrease, and even an increase, in the AV-volume fraction was found
      in liver parenchymal cells of the unilaterally nephrectomized animals. This
      indicates that inhibition of autophagy is not a general response after unilateral
      nephrectomy, but is confined to the growing kidney, where it may represent a
      significant factor in the increase of cytoplasmic mass.

PMID- 1974095
TI  - Enhancement of mucus accumulation in a human gastric scirrhous carcinoma cell
      line (KATO-III) by fibroblast-tumor cell interaction.
AB  - Human fibroblasts (WI-38 cells) were found to enhance mucus accumulation by human
      scirrhous carcinoma cells (KATO-III cells). Coculture of KATO-III with WI-38
      cells resulted in enlargement of the KATO-III cells and increases in the
      proportions of PAS- and colloidal iron-positive KATO-III cells. These
      morphological alterations were reversed when the KATO-III cells were again
      cultured without WI-38 cells. Conditioned media from cultures of WI-38 cells or
      cocultures of KATO-III and WI-38 cells induced the same morphological alterations
      in KATO-III cells, suggesting that WI-38 cells produce a factor or factors that
      enhance mucus accumulation in KATO-III cells. This factor seemed to be a protein
      with a molecular weight of more than 10,000 daltons.

PMID- 1974097
TI  - Age-related hyperplasia of the thymus and T-cell system in the Buffalo rat.
      Immunological and immunohistological studies.
AB  - This report describes the development of hyperplasia of both the thymus and the
      peripheral T-cell system with advancing age in the Buffalo rat. Buffalo/Mna rats
      do not show age-related thymic involution, but rather develop thymic hyperplasia
      with advancing age. This thymic growth is expansile and there is no infiltration
      of the surrounding tissues. Because the enlarging thymus occupies the thoracic
      cavity, most of the rats die of respiratory failure by the age of 24 months.
      Thymic enlargement is due to primary hyperplasia of cortical epithelial cells and
      the large number of proliferating lymphocytes. The hyperplastic epithelial cells
      are bizarre in shape and strongly positive when stained with Th-3 monoclonal
      antibody (MoAb), anti-thymosin antibody and anti-EGF antibody, but negative with
      Th-4 MoAb. The patterns of distribution of CD-5+, CD-4+ and CD-8+ lymphocytes
      within the hyperplastic thymus are similar to those seen in young rats of other
      species. The high level of T-cell emigration from the thymus to the periphery
      appears to persist throughout life, since the percentage of normal splenic T
      cells also increase with advancing age and exceed 70% of the total by 24 months
      of age. This thymic enlargement with abnormal hyperplasia of cortical epithelial
      cells can be prevented by hypophysectomy.

PMID- 1974098
TI  - Autometallographic demonstration of gold in the adrenal gland of rats exposed to
      sodium aurothiomalate. A light and electron microscopic study.
AB  - The presence of gold was investigated in sections of the adrenal glands from rats
      which had been exposed to intraperitoneal sodium aurothiomalate (32 to 120 mg).
      Gold was histochemically detected in cortical endocrine cells, chromaffin cells
      and in fibroblasts and macrophages of both the cortex and medulla. Invisible
      traces of gold were silver enhanced by autometallography making them readily
      visible at both the light and electron microscopic levels. The intracellular
      staining intensity was dose-dependent. In general, the number as well as the
      staining intensity of individual cells, were highest in the zona glomerulosa and
      zona reticularis. In gold-containing cells the silver-amplified deposits were
      present in lysosomes.

PMID- 1974099
TI  - [Acute reduction of increased atrial natriuretic peptide level and cyclic
      guanosine monophosphate in patients with chronic heart failure caused by beta
      adrenergic stimulation with dopexamine hydrochloride. Correlation with
      hemodynamic parameters].
AB  - In eight patients (63 +/- 8 years) with dilated cardiomyopathy, the acute effects
      of positive inotropic stimulation with dopexamine hydrochloride, a beta-2
      agonistic and DA1-dopaminergic catecholamine, on the plasma levels of ANP and
      cGMP were tested. A four-point dose-response curve was prepared for dopexamine
      from 1 microgram/kg/min to 4 micrograms/kg/min. Each infusion stage lasted 15
      min; ANP and cGMP were taken from the mixed venous blood. Hemodynamic parameters
      were determined by a Swan-Ganz catheter; cardiac output was determined by
      thermodilution. ANP dropped by 40% from 348 +/- 124 pg/ml to 208 +/- 70 pg/ml (p
      less than or equal to 0.01), while cGMP dropped by 25% from 4.8 +/- 1.6 pmol to
      3.6 +/- 1.3 pmol/ml at the time of maximum hemodynamic effect after 1 h. Linear
      regression analyses revealed a significant relationship (p less than or equal to
      0.01) between ANP as the independent variable and cGMP as the dependent variable.
      The hemodynamic determinants of the ANP concentration proved to be--independently
      of each other--the pulmonary capillary wedge pressure (p less than or equal to
      0.01) and the mean right atrial pressure (p less than or equal to 0.01). The
      results show that chronically elevated ANP and cGMP levels can be strikingly
      reduced within a short time, whereby ANP and cGMP show similar kinetics. The
      results suggest a use of ANP and cGMP as humoral parameters in the therapy
      control of chronic heart failure.

PMID- 1974100
TI  - [Acute hemodynamic effects of the vasodilator beta blocker carvedilol in heart
      failure].
AB  - The beta-blocker carvedilol has been shown to induce vasodilation in patients
      with coronary artery disease. In a double-blind, randomized, placebo-controlled
      cross-over study, we looked for the acute vasodilating effect after i.v.
      administration in patients with heart failure. In 10 patients with coronary
      artery disease and six patients with dilated cardiomyopathy, all with an ejection
      fraction lower than 40%, the rate-pressure-product during supine ergometry and
      Swan-Ganz-catheterization rose to a significantly smaller extent after 5 mg
      carvedilol i.v. compared to placebo. This was mainly due to a lower heart rate at
      rest and during exercise, while blood pressure was not changed compared to
      placebo. Calculated total peripheral resistance during exercise after carvedilol
      was higher--significantly so in the CAD-group--than after placebo. These results
      show that in patients with heart failure, an acute vasodilating effect of i.v.
      carvedilol is not detectable.

PMID- 1974101
TI  - Quantitative and qualitative analysis of DNA extracted from postmortem muscle
      tissues.
AB  - DNA extracted from 33 postmortem muscle specimens was analyzed using MZ 1.3, a
      hypervariable minisatellite probe, as well as locus-specific minisatellite probes
      (g3, MS1 and MS43). After storage at -25 degrees C for 10 months, DNA from all
      the samples was partially (approximately 21% of total DNA) degraded even when
      autopsy was performed 1 day postmortem. However, more than 90% of DNA samples up
      to at least 3 days postmortem were suitable to obtain good restriction fragment
      length polymorphism (RFLP) patterns. When small strips of specimen were stored
      for 8 days at room temperature in moist chambers, approximately 42% of total DNA
      was degraded. Only 30% of these DNA samples still showed good RFLP patterns.
      However, no obvious relation between qualities of DNA analyzed by detection of
      RFLP and quantities of total and high-MW DNA became apparent. A case of familial
      relationship was ascertained by DNA fingerprints. Since DNA of good quality can
      be recovered from muscle tissues in large quantities, DNA extraction from muscle
      tissues and detection of RFLP patterns should be very useful for individual
      identification in autopsy cases.

PMID- 1974103
TI  - Chemical mediators in hypersensitivity reactions.
AB  - The study of chemical mediators is essential in clarifying the mechanism of
      hypersensitivity reactions. Recent advances in this field have been made
      particularly with the arachidonic acid metabolites, several of which strongly
      contract smooth muscle, attract granulocytes to inflammatory foci and lead to
      increased vascular permeability. These functions play a crucial role in allergic
      reactions. Furthermore these mediators might work to modulate the intracellular
      network which mediates the complicated inflammatory process of hypersensitivity
      reactions.

PMID- 1974104
TI  - Non-right-handedness and maleness correlate with tardive dyskinesia among
      patients taking neuroleptics.
AB  - Forty-eight consecutive psychiatric outpatients receiving neuroleptics were
      assessed for handedness and the presence of tardive dyskinesia (TD). Twenty-seven
      patients had TD and 21 did not. Twenty-one of the patients with TD had some
      degree of non-right-handedness compared with 3 of the patients without TD. These
      results were found to be statistically significant. Maleness also correlated with
      the presence of TD, but the results were less robustly significant. These
      findings indicate that non-right-handedness and maleness may correlate with the
      risk of developing TD. To the author's knowledge, these findings have not been
      previously reported.

PMID- 1974102
TI  - Effect of dietary environment on the development of impaired glucose tolerance
      and pancreatic hormone secretion in neonatal streptozocin-treated (NSZ) rats.
AB  - The effects of four different diets, a balanced (BD), a high protein (HP), a high
      fat (HF), and a high carbohydrate (HC) diet on glucose tolerance and pancreatic
      hormone secretion were compared during the ten-week period immediately after
      weaning in rats having glucose intolerance induced by streptozocin in the
      neonatal period (NSZ). Feeding HF or HC produced decrease in calorie intake and a
      delay in body weight increase. All NSZ rats showed glucose intolerance as adults;
      the HF rats showed a further deterioration of glucose tolerance and a decreased
      insulinogenic index after oral glucose loading. Plasma insulin levels of HC rats
      were lowest. The glucose-induced insulin and somatostatin secretion from the
      isolated perfused pancreas was almost identical in all four groups. The arginine
      induced insulin and glucagon secretion was decreased in HF and HC rats, compared
      to both HP and BD rats, but somatostatin secretion was not. These results
      indicate that a high fat or high carbohydrate dietary environment is an important
      factor in the development of glucose intolerance and in the impairment of
      pancreatic hormone responsiveness to stimulation.

PMID- 1974105
TI  - Neurotransmitter activation of second messenger pathways for the control of
      growth cone behaviors.
AB  - The generation and regeneration of neuronal form and connectivity both
      undoubtedly rely upon the integration of intrinsic and extrinsic information of
      many kinds. Our work has demonstrated that the concentration and spatial
      distribution of intracellular calcium is a key locus of integration of such
      information. Through a delicate balance of mechanisms that raise free calcium and
      mechanisms that lower free calcium, a steady state level is achieved that appears
      to have significant regulatory control over neuronal growth cone behavior. Cues,
      both internal and external, alter intracellular calcium levels, and consequently
      alter growth cone behavior. It is through the alteration of the various
      components of calcium homeostasis that we envision the complexities of neuronal
      architecture and connectivity may be fine-tuned throughout the life histories of
      neuronal ensembles.

PMID- 1974106
TI  - Dibutyryl cyclic AMP treatment of astrocytes in primary cultures as a substitute
      for normal morphogenic and 'functiogenic' transmitter signals.

PMID- 1974107
TI  - Developmental expression of amyloid precursor protein in normal and trisomy 16
      mice.

PMID- 1974108
TI  - [Transfixation in treatment of comminuted fractures of the distal end of the
      radius].
AB  - In comminuted fractures of the distal radius we apply our own method of
      transfixation. A Kirschner-wire is put through the bases of the metacarpal II-V,
      in addition an above elbow-plaster is applied. 47 persons (38 female, 9 male,
      age: phi 69 a) treated by this method have been checked-up after 16 months (26-5
      months). In spite of the predominantly negative prognosis of the C3 fracture,
      according to the scheme of AO, we found out in our check-up considering
      principles of Sarmiento a good or a very good result in 41 cases (87%).

PMID- 1974109
TI  - [Bore puncture wire tension fixation].
AB  - The simplicity of tension band wire fixation with Kirschner pins and wire loop
      explains the wide propagation of this operative method. The most frequent
      complication results from the migration of the pins. The development of an
      aperture pin eliminates this risk.

PMID- 1974110
TI  - [Corrective osteotomy of the head of the tibia in primary and secondary
      gonarthrosis--a para-articular operation].
AB  - The corrective osteotomy at the head of the tibia with degenerative or
      posttraumatic medial or lateral gonarthrosis and misalignment of the axis is
      until today a procedure to be recommended prior to a total or partial
      implantation of an endoprosthesis. The main advantage in comparison with a mono
      condylar prosthesis is the removal of the causal damage of the misalignment. Old
      age and general relative risks are no contraindications to this procedure. The
      method used most in the operative technique is the correction of valgus deviation
      at the head of the tibia after osteotomy of the fibula with stabilization with a
      fixateur externe. On the whole, the risk of the operation is very low, the main
      complication is the lesion of the nervus peronaeus. With regard to the subjective
      result from the patients point of view the most important aspect is the relief or
      disappearance of pain, which is reached in comparison with a partial prosthesis
      of the knee joint with similar security. About two thirds of the patients are
      subjectively contempt with the results of the operation within a time of three to
      five years.

PMID- 1974111
TI  - [Results of hip joint replacement with ceramics partial endoprostheses].
AB  - Report about our 5 years experience with cementless and cemented partial ceramic
      hip prostheses in altogether 58 cases. Indication, in old age, mostly in case of
      fresh or elder femoral neck fracture; in younger age, chiefly in case of partial
      femoral head necrosis and preserved cartilage of acetabulum. Typical complication
      of this type of prosthesis: early luxation, especially in case of acetabular
      dysplasia, which, therefore, has to be regarded as contraindication for
      hemiarthroplasty. Satisfying subjective and objective middle-term-results in
      older age. Failure of arthroplasty with necessity of later implantation of
      acetabular component only in two cases of osteoporotic bone destruction. In
      younger age, the results weren't that satisfying. Because of higher activity and
      strain there was a higher rate of wear of acetabular cartilage; twice, we had to
      perform later implantation of ceramic socket, up to now.

PMID- 1974112
TI  - [Metabolic diseases of bones. Catamnestic study of the incidence and kind of
      problems in surgical treatment].
AB  - By a catamnestic study at Orthopedic Department of Homburg/Saar University Clinic
      156 courses of variant constitutional diseases of bone (1965-1986) were recorded.
      The frequencies of primary spontaneous fractures, fracture healing-disturbances,
      refractures and pseudarthroses after operative management of bone lesions or
      correction-osteotomies were of special interest. While there was no increased
      rate of traumatic or spontaneous lesions or prolongated healing-rate in case of
      Rickets and M. Ollier, those complications with need of osteosynthetic measures
      were more often due to M. Paget and M. Jaffe-Lichtenstein. As expected,
      osteogenesis imperfecta represented the highest rate of osseous lesions; an
      uneven situation was found among multiple/generalized epi- and metaphyseal
      dysplasias.

PMID- 1974113
TI  - [Teutschlander disease--a rare benign soft tissue calcinosis. Case report].
AB  - Morbus Teutschlander or tumoral calcinosis is a rare soft tissue calcification.
      We report the case of a 65 years old white female, who presented 40 years after a
      crush trauma a bilateral tumoral calcinosis of the lower leg. We describe
      diagnosis, therapy and progress.

PMID- 1974114
TI  - [Evaluating histologic findings of the rotator cuff of the shoulder].
AB  - Tearing of the rotator cuff is normally due to degenerative changes of the
      supraspinator tendon. The vascular situation as well as histological findings in
      elderly patients--oedema, necrosis and hyalinosis--are reasons for the defect. A
      classical rupture caused by a real trauma is very rare; it is therefore better to
      call these typical findings "rotator cuff defect". Regular histological
      examination is necessary for the classification as traumatic rupture or
      degenerative defect.

PMID- 1974115
TI  - [Cerebral blood flow velocity. A prognostic factor following severe
      craniocerebral trauma?].
AB  - Head injuries lead to changes in cerebral blood flow velocity (BFV)--measured
      with the transcranial Doppler ultrasonography--in 19 out of 31 patients, i.e.
      61%. In 12 cases there was an immediate increase of BFV following the injury or
      within the first 7 days, often parallel with an increase of the intracranial
      pressure. On the other hand in 2 out of 4 cases with chronic subdural haemorrhage
      there was a decrease of the BFV. With routine use of transcranial doppler
      ultrasound in neurosurgical intensive care, acute changes in BFV along with
      clinical deterioration may indicate the need for a repeat CT and eventually a
      surgical intervention.

PMID- 1974116
TI  - [Local complications following implantation of Biorod].
AB  - We report on 2 cases with complications after implantation of Biorod. These seem
      to be the result of tissue reaction to the material. According to the
      manufacturer, such complications have been observed in 6 to 10% of the cases.
      These observations have not been published so far.

PMID- 1974117
TI  - [Secondary fracture of the coxal end of the femur].

PMID- 1974118
TI  - [Arthroscopy of traumatic hemarthrosis following sports injuries. A 5 year
      analysis].
AB  - This retrospective study was made to evaluate the significance of different
      sports activities that cause variable haemarthrosis with intraarticular lesions
      of the knee joint. Throughout 1984 to 1988 arthroscopy was performed in 337
      patients with acute haemarthrosis. The average time between trauma and
      arthroscopy was 8 days. ACL rupture was diagnosed in most of these cases.
      Regarding the different types of sport activities ACL lesions were found in
      skiers (74%), other winter sports (47%), soccer (53%), tennis and squash (58%),
      athletics (41%) and indoor (61%). Peripheral meniscus tears associated with
      haemarthrosis were found in 36% and patellar dislocations in 8%. Isolated MCL
      ruptures were diagnosed clinically and arthroscopy was not performed in these
      cases. Throughout 1987 isolated ACL ruptures were fixed by reattachment. This
      technique was not continued any longer and ACL replacement by patellar tendon as
      bone-ligament-bone was performed routinely since 1988 in those patients, who
      required surgery. 56 patients required ACL reconstruction following conservative
      treatment because of ACL deficiency, when they went back to sports activities.
      Longitudinal peripheral meniscus tears were fixed by the scape in inside-out
      technique.

PMID- 1974119
TI  - [The physician's responsibility for patient education regarding treatment
      alternatives].

PMID- 1974120
TI  - Addiction potential of benzodiazepines and non-benzodiazepine anxiolytics.
AB  - This paper reviews the addiction potential of all benzodiazepines currently
      available in the U.S.A. as well as several non-benzodiazepine anxiolytic drugs.
      Addiction potential was assessed by separately considering the potential for
      these drugs to produce three different phenomena of addiction; namely, physical
      dependence, psychological dependence and deleterious consequences. This review
      focuses on human studies conducted with research volunteers outside the
      therapeutic context and also on clinical studies conducted with patients
      receiving treatment in the therapeutic context. It is concluded that
      benzodiazepines have a reduced addiction potential in comparison to the
      predecessor barbiturates. Conclusions regarding the relative addiction potential
      of several non-benzodiazepine anxiolytics are difficult due to a paucity of data;
      however limited evidence suggests a reduced addiction potential for several of
      these compounds. Within the benzodiazepine class, qualitative differences in
      addiction potential between individual drugs are not well established.

PMID- 1974121
TI  - Addictiveness of central stimulants.
AB  - Central stimulants have been abused since their inception and we are currently in
      the midst of a cocaine epidemic that challenges our resources and capabilities.
      Through their actions on powerful endogenous reward centers, central stimulants
      produce intense euphoria that reinforces subsequent usage and eventual
      dependence. Considerable evidence indicates that the activation of dopamine
      circuits mediates stimulant reward. With regard to cocaine, it has been
      hypothesized that depletion of central dopamine leads to craving. Euphoria and
      craving, the key dynamics of stimulant addiction, may therefore result largely
      from neurochemical alterations of dopamine systems in the brain's reward center.
      Progressive deterioration of the stimulant addict involving medical, psychiatric,
      and psychosocial impairment occurs rapidly, underscoring the addiction potential
      of these agents. Tolerance, sensitization and withdrawal phenomena are discussed
      from clinical and neurochemical perspectives.

PMID- 1974123
TI  - [Treatment of patients with disorders of the ovulatory function of central
      etiology with preparations affecting adrenergic mechanisms].
AB  - A treatment protocol has been proposed for patients with luteal phase inadequacy
      of central origin employing isodrin stimulation of beta-adrenergic receptors on
      days 5 to 10 of the cycle and fetanol stimulation of alpha-adrenergic receptors
      on days 10 to 14. This protocol is recommended for use in ovarian function
      normalization, both alone and in combination with hormonal therapy.

PMID- 1974122
TI  - The fragile X: progress toward solving the puzzle.

PMID- 1974124
TI  - Inhibition of anti-IgE induced skin response in normals by formoterol, a new beta
      2-adrenoceptor agonist, and terbutaline. 1. Dose response relation and duration
      of effect on the early wheal and flare response.
AB  - The intention of the present study was to compare formoterol and terbutaline
      regarding ability to inhibit immediate wheal and flare responses (WFR) to anti
      human IgE with focus on the duration of anti-WFR action. Formoterol is a novel
      beta 2-adrenergic agonist with a prolonged duration of bronchodilation capacity
      after inhalation. The drugs injected intradermally 2 min prior to challenge with
      anti-IgE in volunteers produced a dose-dependent inhibition of the WFR in the
      range 1pg-100ng (formoterol) and 1ng-1 microgram (terbutaline). Formoterol was 70
      times (flare) and 25 times (wheal) more potent (ID40) than terbutaline on a
      weight basis. The duration of the anti-WFR action for formoterol, injected in a
      25 times lower dose than terbutaline, was significantly longer, namely greater
      than 24 h versus 8 h for terbutaline. The histamine-induced wheal reaction was
      attenuated by 15% and 25% by terbutaline and formoterol, respectively. The
      results indicate a higher beta 2-receptor activity for formoterol with respect to
      inhibition of IgE-dependent mast cell mediator release in addition to an anti
      leak effect exerted by both drugs. The prolonged duration of antagonistic effect
      by formoterol on the WFR to anti-IgE might be due to the lipophilic property of
      the drug, with an expected higher retention of formoterol at the target tissue
      compared with the more hydrophilic compound terbutaline.

PMID- 1974125
TI  - Use of DNA probes for differentiation of spotted fever group and other
      rickettsiae.

PMID- 1974126
TI  - Molecular genetics of populations of intracellular bacteria: the spotted fever
      group rickettsiae.
AB  - The population structure of tick-borne rickettsiae show the following
      characteristics: (1) the amount of genetic differentiation between strains within
      subpopulations is very small. (2) The evolution of the subpopulations does not
      fit into models based on either host or geographic similarities, suggesting the
      need for more information on the frequency of vertical versus horizontal
      transmission of strains between hosts. (3) The species are highly clonal, with
      little evidence of genetic exchange between populations. (4) The dominant class
      of genetic change is single-nucleotide point mutation. No evidence for major
      rearrangements was observed. (5) Differentiation between species of the spotted
      fever group is equivalent to that seen between local strains of E. coli.

PMID- 1974127
TI  - Genetic relationships among the members of the family rickettsiaceae as shown by
      DNA restriction fragment polymorphism analysis.
AB  - The genetic diversity of members of the genus Rickettsia was examined using
      restriction site polymorphisms found within a series of DNA fragments scattered
      throughout the genome. Rickettsia belli, R. akari, and R. australis were the most
      divergent species when compared to the other species examined. These three
      species were also not closely related to each other. The other examined species
      were more tightly clustered. This survey also examined the genetic diversity
      within several species. The unexpected finding of this survey is that several
      species of rickettsia are as closely related to the surveyed strains of R.
      rickettsii as these strains are to each other. These results indicate that R.
      sibirica, R. parkeri, R. rickettsii, and an unnamed isolate from Africa are
      likely to be strains of a single rickettsial species of worldwide distribution.
      R. conorii was very closely related to this R. rickettsii-containing group but is
      likely to remain in a genetically distinct category as the data base expands.

PMID- 1974128
TI  - Comparison of properties of isolated ehrlichiae and scrub typhus rickettsiae.

PMID- 1974129
TI  - Cardiovascular and neurohumoral responses following burn injury.
AB  - Cardiovascular and endocrine responses were evaluated in 12 adult patients over a
      5-day period following 30% to 66% burn injury. Heart rate, mean arterial
      pressure, central venous pressure, pulmonary capillary wedge pressure, cardiac
      output, systemic vascular resistance, and stroke volume were measured. Plasma
      concentrations of angiotensin II, atrial natriuretic peptide, vasopressin,
      neuropeptide Y, norepinephrine, and epinephrine were measured. On the day of burn
      injury, systemic vascular resistance was markedly elevated, and stroke volume and
      cardiac output were low, but all normalized by day 3, and cardiac output and
      stroke volume increased by day 5 without significant changes of central venous
      pressure or pulmonary capillary wedge pressure. Mean arterial pressure and heart
      rate did not change significantly over the 5-day period. Vasopressin, angiotensin
      II, neuropeptide Y, norepinephrine, and epinephrine concentrations in plasma were
      elevated on admission. Vasopressin concentrations were elevated 50 times normal
      on admission and returned to normal levels by days 4 to 5. Plasma atrial
      natriuretic peptide concentrations were normal on admission and increased
      significantly on days 3 to 5. The reciprocal relationship between systemic
      vascular resistance and cardiac output and between vasopressin and atrial
      natriuretic peptide correlate with each other and the observed physiologic events
      that occurred following burn injury and resuscitation. All of these changes in
      cardiac performance occurred without significant alterations in preload or
      afterload as measured by central venous pressure, pulmonary capillary wedge
      pressure, and mean arterial pressure. Increases in plasma levels of atrial
      natriuretic peptide correlated with the increased stroke volume and cardiac
      output observed in these patients. The results of this study are consistent with
      the conclusion that the extreme elevations of plasma vasopressin levels
      contribute to the vascular complications of increased systemic vascular
      resistance and decreased cardiac output and contractility seen following burn
      injury.

PMID- 1974130
TI  - Restriction fragment pattern analysis of genomes from French isolates of suis
      herpes virus 1 (Aujeszky's disease virus).
AB  - Purified DNA from 45 isolates of suis herpes virus 1 (SHV1) collected between
      1980 and 1987 from clinical outbreaks of Aujeszky's disease on French farms was
      compared by restriction fragment pattern (RFP) analysis. The BamHI generated RFPs
      were found to be distinguishable, confirming RFP analysis as a potential
      epidemiological tool. The RFP could be assigned to two established major
      electrophoretic types and different subtypes. The RFP analysis indicated that the
      majority of outbreaks were caused by ADV with a central European genome type. The
      heterogeneity of RFPs among PRV isolates recovered from the central nervous
      system, lung, and foetus was not restricted specifically to one clinical entity.
      Variations in the virulence of the 45 isolates studied in mice, chicks, or
      piglets were unrelated to the RFP subtypes. One unusual RFP has been described
      for one strain of low virulence.

PMID- 1974132
TI  - [Benzodiazepines: patterns of use, tolerance and dependence].
AB  - The authors review recent studies on benzodiazepine, the most largely used drug
      for insomnia and anxiety. In this paper are summarized: the development, patterns
      of use and abuse, mechanism of action, development of differential tolerance to
      its many effects, and the phenomena of withdrawal and dependence on the
      benzodiazepines.

PMID- 1974131
TI  - Nuclease treatment results in high specific purification of Creutzfeldt-Jakob
      disease infectivity with a density characteristic of nucleic acid-protein
      complexes.
AB  - Representative preparations of partially purified Creutzfeldt-Jakob disease
      (CJD), including disaggregated density gradient fractions, were treated with a
      variety of nucleases. RNases as well as exhaustive digestions with micrococcal
      nuclease did not significantly diminish infectivity, but resulted in an
      approximately 7,000-fold specific purification of infectivity with respect to
      nucleic acid. Protected nucleic acids included species of up to 2,000 bases in
      length. After nuclease treatment, infectivity co-migrated with nucleic acid
      protein complexes at a density of 1.27 g/cm3 in sucrose. Substantial specific
      protein purification were also achieved in the gradient step (approximately
      11,000-fold), where 70% the host Gp34 ("prion protein") as well as other free
      proteins separated from infectivity. These CJD purifications are better than
      those previously attained in scrapie, and may be useful for further studies of
      non-host protein and nucleic acid species. The data are consistent with the
      hypothesis that CJD-like agents are composed of nucleic acid-protein complexes.

PMID- 1974133
TI  - The relative importance of various mosquitoes for the transmission and control of
      dog heartworm in south-eastern Australia.

PMID- 1974134
TI  - Benzodiazepine receptor ligand influences on acquisition: suggestion of an
      endogenous modulatory mechanism mediated by benzodiazepine receptors.
AB  - In rats, pretraining ip administration of the central benzodiazepine receptor
      antagonist, flumazenil (5.0 mg/kg), or of the inverse agonist, n-butyl-beta
      carboline-3-carboxylate (BCCB) (0.2 or 0.5 mg/kg), facilitated retention of a
      step-down inhibitory avoidance task; the central agonists, clonazepam and
      diazepam (0.4 or 1.0 mg/kg), had an opposite effect, and the peripheral agonist,
      4'-chlordiazepam (1.25 or 6.25 mg/kg), was without effect. Pre- but not post
      training flumazenil (2.0 mg/kg) blocked the effect of BCCB (0.5 mg/kg),
      clonazepam (1.0 mg/kg), or diazepam (1.0 mg/kg) given also pretraining. The post
      training administration of all of these drugs had no effect on retention of the
      avoidance task. Flumazenil (5.0 mg/kg) and BCCB (0.5 mg/kg), given before
      training, enhanced retention test performance of habituation to a buzzer but not
      of habituation to an open field. In the three tasks studied, none of the drugs
      used had any appreciable effect on training session parameters. These results
      suggest that there is an endogenous mechanism mediated by benzodiazepine
      agonists, sensitive to inverse agonists, that normally down-regulates acquisition
      of certain behaviors; this mechanism becomes activated only when the tasks
      involve or occur with a certain degree of stress or anxiety (i.e., inhibitory
      avoidance or habituation to the buzzer) and not in less stressful or anxiogenic
      tasks (i.e., habituation to an open field).

PMID- 1974135
TI  - Somatostatin binding to chicken adenohypophysial membranes.
AB  - [125I-Tyr1]-Somatostatin (SRIF)-binding sites were demonstrated on crude plasma
      membrane preparations from chicken pituitary glands. These binding sites were
      saturable and of high affinity (dissociation constant less than 1.0 nM) and low
      capacity (maximal binding capacity less than 200 fmol/mg protein) and were
      specific for SRIF moieties. The number and affinity of these binding sites in the
      caudal lobe of the pituitary, in which somatotrophs predominate, were similar to
      those in the cephalic lobe, in which lactotrophs and thyrotrophs are confined.
      Gonadotrophs are present in the caudal lobe, but whereas exogenous SRIF inhibited
      secretagogue-induced GH release from incubated pituitary glands, it had no effect
      on basal or secretagogue-induced LH release. The half-maximal binding of SRIF to
      the caudal lobe membranes (3 nM) was similar to that required for half-maximal
      suppression of TRH-induced GH release, suggesting a role for these binding sites
      in the regulation of GH secretion in birds.

PMID- 1974137
TI  - [Astemizole: its pharmacokinetics and pharmacologic properties].
AB  - Astemizole (Hismanal) is a chemically novel compound selected from a series of
      piperidinylaminobenzimidazoles. Further preclinical pharmacological
      investigations were initiated by experiences with other drugs in the same field.
      The aim of this review is to illustrate new pharmacological data on astemizole.
      Astemizole showed the lowest ED50 and the longest duration in mast cell-mediated
      shock. Binding characteristics to histamine H1 receptors were specificity,
      selectivity and long duration. Lack of effects on the wakefulness-sleep cycles
      was evidenced. An equal bioavailability of the drug was demonstrated with
      different formulations, dosing and food intake. High plasma levels of
      desmethylastemizole, the major metabolite, and longer half-life than for
      astemizole, contribute partly to the antihistamine activity. On chronic
      administration relative amounts of both molecules in the peripheral compartment
      are most likely responsible for the expected pharmacological effect. The time
      course of kinetics shows, the peak plasma levels of the unchanged astemizole
      followed by a gradual take-over by desmethylastemizole. In patients with hepatic
      or renal insufficiency the pharmacokinetic background was similar to healthy
      volunteers.

PMID- 1974136
TI  - Evidence for differential effects of noradrenaline and somatostatin on
      intracellular messenger systems in rat islets of Langerhans.
AB  - The mechanisms involved in inhibition of insulin secretion by somatostatin and
      noradrenaline were compared in order to establish whether the receptors for these
      agents are coupled to similar effector systems in the pancreatic B cell. Both
      agents significantly reduced forskolin-induced adenylate cyclase activity in
      islet homogenates, although noradrenaline was more effective than somatostatin.
      The capacity of noradrenaline to inhibit insulin secretion was largely unaffected
      by agents that increase intracellular cyclic AMP, whereas the effect of
      somatostatin as an inhibitor was markedly reduced under these conditions. Both
      noradrenaline and somatostatin inhibited the stimulation of insulin secretion
      induced by K+ depolarization, but different mechanism were involved. Somatostatin
      significantly inhibited K(+)-stimulated 45Ca2+ efflux and influx in islets, while
      noradrenaline exerted only a minor influence on these processes. The data
      indicate that noradrenaline controls insulin secretion by a mechanism which
      operates beyond the level of intracellular messenger generation. In contrast,
      somatostatin exerts at least part of its inhibitory effect on insulin secretion
      by directly controlling islet cell Ca2+ influx in a manner which may be regulated
      by cyclic AMP.

PMID- 1974138
TI  - [Pain control. Pharmacological methods].

PMID- 1974139
TI  - [Morphological findings in cryptorchism in the adult male].
AB  - Cryptorchidism, the most common endocrine disturbance in the newborn, is still
      present in 0.3% of all postpubertal men as monolateral or bilateral condition.
      The undescended testis, in postpubertal age, is permanently damaged, so about 80%
      of cryptorchids are subfertile or definitively sterile. In the present study we
      relate our observations on structure and ultrastructure of testicular biopsies
      obtained from 29 cryptorchid men aged from 16 to 64. The individual pattern of
      morphological alterations is closely related to age and position of undescended
      testis. The following aspects are recognizable in cryptorchid testis: 1)
      seminiferous tubules reduced in size and irregular in shape; 2) tubular lumen
      occluded; 3) reduced germ cell population; 4) altered stages of spermatogenesis;
      5) increased thickness of spermatogonia layer; 6) vacuolization of germ cells; 7)
      polynucleated germ cells; 8) acrosomal deformities; 9) delivery of immature germ
      cells; 10) Sertolisation of the seminiferous tubule; 11) immature Sertoli cells;
      12) multilayered and thickened basement lamina; 13) peritubular fibrosis; 14)
      vascular fibrosis; 15) vacuolisation of Leydig cells; 16) interstitial
      mastocytosis. The findings present a mosaic of the morphological events, that are
      characteristic not only of the undescended testis but also of numerous testicular
      pathologies as well as of other conditions as prolonged hyperthermia,
      experimental ischaemia and senescence.

PMID- 1974140
TI  - Gene mapping and the human genome mapping project.

PMID- 1974141
TI  - Homeodomain proteins and the regulation of gene expression.

PMID- 1974142
TI  - Hormonal responses to cardiac surgery: effects of sufentanil, somatostatin and
      ganglion block.
AB  - We have investigated the effect of the addition of somatostatin and trimetaphan
      to sufentanil 20 micrograms kg-1 on the hormonal responses to cardiac surgery and
      compared the changes with a control group receiving sufentanil and sodium
      nitroprusside. Eighteen patients undergoing elective valve replacement surgery
      were studied. Patients who received somatostatin and trimetaphan in addition to
      sufentanil had significantly smaller serum growth hormone and plasma glucagon
      concentrations compared with those who received sufentanil and sodium
      nitroprusside. The cortisol response to surgery was inhibited in both groups.
      There were no significant differences in catecholamine concentrations between the
      two groups. There was no effect of the additional inhibition of glucagon and
      growth hormone on circulating concentrations of glucose and lactate, but plasma
      concentrations of non-esterified fatty acids increased significantly. Thus the
      addition of somatostatin increased the suppression of the hormonal response to
      cardiac surgery by sufentanil.

PMID- 1974143
TI  - Beta-adrenoceptor blockade and hypoglycaemia. A randomised, double-blind, placebo
      controlled comparison of metoprolol CR, atenolol and propranolol LA in normal
      subjects.
AB  - 1. The effect of 1 week of treatment with propranolol LA (160 mg), atenolol (100
      mg) and metoprolol CR (100 mg) on awareness of and the physiological responses to
      moderate hypoglycaemia were compared with placebo using a randomised, cross-over
      design in 12 healthy volunteers. 2. All three beta-adrenoceptor antagonists
      reduced resting heart rate, systolic blood pressure and heart rate responses to
      submaximal exercise compared with placebo. 3. Under hyperinsulinaemic (60 mu m-2
      min-1) clamp conditions, at a blood glucose of 2.5 mmol l-1, atenolol prevented
      the rise in systolic and atenolol and metoprolol CR prevented the fall in
      diastolic blood pressure usually associated with hypoglycaemia. At this level of
      hypoglycaemia, the expected increase in heart rate was inhibited by atenolol but
      not metoprolol CR. Pre-treatment with propranolol LA resulted in a significant
      pressor response and a bradycardia during hypoglycaemia. In addition the normal
      increase in finger tremor was abolished by propranolol LA. 4. During
      hypoglycaemia all three beta-adrenoceptor blockers augmented sweating compared
      with placebo but hypoglycaemic symptoms, awareness and slowing of reaction time
      were the same with drugs and placebo. 5. The rise in plasma adrenaline and other
      counter-regulatory hormones during hypoglycaemia was enhanced by beta
      adrenoceptor blockade. 6. We conclude that beta-adrenoceptor antagonists modify
      the physiological and hormonal responses to, but do not adversely affect
      awareness of, moderate hypoglycaemia in healthy volunteers.

PMID- 1974144
TI  - Haemodynamic dose-response effects of UK-52,046 in ischaemic disease with or
      without impaired left ventricular function.
AB  - 1. The haemodynamic effects of a new cardioselective postsynaptic alpha 1
      adrenoceptor antagonist UK-52,046, were evaluated in 25 patients with stable
      coronary disease, with or without impaired left ventricular function. At rest the
      haemodynamic effects to two dose-response regimens were determined. In an initial
      eight patients 0.125, 0.125 and 0.25 micrograms kg-1 were administered
      peripherally at 15 min intervals; the haemodynamic measurements were determined
      between 10 to 15 min after each dose. In a further 17 patients, the dose regimen
      was doubled yielding a cumulative dose-regimen of 0.25, 0.5 and 1.0 micrograms kg
      1. The exercise effects were determined by comparison of measurements during 4
      min of supine sub-maximal bicycle exercise at a fixed workload before and after
      drug treatment. 2. At rest, the lower dose regimen of UK-52,046 significantly
      reduced systemic mean arterial blood pressure (-5 mm Hg; P less than 0.05) and
      increased cardiac index (+0.2 l min-1 m-2, P less than 0.01). The higher dose
      regimen of UK-52,046 reduced systemic mean arterial blood pressure (-7 mm Hg; P
      less than 0.01), pulmonary artery occluded pressure (PAOP) (-2 mm Hg, P less than
      0.01) and vascular resistance index (-314 dyn s cm-5 m2; P less than 0.05) with
      an increase in heart rate (+7%, P less than 0.05) and cardiac index (+0.2 l min-1
      m-2, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1974145
TI  - Pseudomonas aeruginosa exotoxin A: alterations of biological and biochemical
      properties resulting from mutation of glutamic acid 553 to aspartic acid.
AB  - Glutamic acid 553 of Pseudomonas aeruginosa exotoxin A (ETA) was identified
      earlier as a putative active-site residue by photoaffinity labeling with NAD.
      Here ETA-E553D, a cloned form of the toxin in which Glu-553 has been replaced by
      aspartic acid, was purified from Escherichia coli extracts and characterized.
      Cytotoxicity of the mutant toxin for mouse L-M cells was less than 1/400,000 that
      of the wild type. The mutation caused a 3200-fold reduction in NAD:elongation
      factor 2 ADP-ribosyltransferase activity, as estimated by assays with an active
      fragment derived from the toxin by digestion with thermolysin. NAD glycohydrolase
      activity was reduced somewhat less, by a factor of 50, and photoaffinity labeling
      with NAD by a factor of 2. We detected less than 2-fold change in the values of
      KM for NAD or elongation factor 2 and no change in KD for NAD, as determined by
      quenching of protein fluorescence. The drastic reduction of ADP
      ribosyltransferase activity therefore results primarily from an effect of the
      mutation on kcat, implying that Glu-553 plays an important and possibly direct
      role in catalyzing this reaction. The effects of the E553D mutation are similar
      to those of the E148D mutation in diphtheria toxin, supporting the notion that
      these two Glu residues perform the same function in their respective toxins.

PMID- 1974146
TI  - Probing the transglutaminase-mediated, posttranslational modification of proteins
      during development.
AB  - Sphaerechinus granularis eggs were fertilized in seawater in the presence of 0.2
      mM dansylcadaverine, and development was allowed to take place with this compound
      in the medium. gamma-Glutamyldansylcadaverine, indicative of the utilization of
      the amine tracer by intrinsic transglutaminase, was isolated from the embryonic
      proteins, and identity of the product with the chemically synthesized gamma
      glutamyl derivative of dansylcadaverine was confirmed. Covalent labeling of
      proteins occurring during development was examined by means of electrophoresis in
      NaDodSO4, followed by immunoblotting with an antibody that specifically
      recognized the dansyl hapten. There was an increase in the total uptake of the
      tracer at an essentially constant rate with each cell division, from 2- to 8- and
      64-cell stages. Moreover, multiple protein labeling was evident in all specimens.
      The described concept of studying posttranslational modifications in vivo by
      transglutaminase through detection of the haptenic or specific ligand
      recognizable group of an incorporated small amine substrate will undoubtedly be
      of general utility for probing the functions of this family of enzymes in other
      cell types as well.

PMID- 1974148
TI  - Purification and characterization of N-acetylmuramoyl-L-alanine amidase from
      human serum.
AB  - Purification to homogeneity of the N-acetylmuramoyl-L-alanine amidase
      (mucopeptide amidohydrolase, EC 3.5.1.28) from human serum has been achieved with
      a high yield. By molecular sieving chromatography, a molecular weight of 120,000
      130,000 has been found for the native enzyme. Polyacrylamide gel electrophoresis
      under native conditions gave a unique band of Mr = 125,000. The same technique
      performed under denaturing conditions revealed that the protein is a dimer
      composed of one subunit of Mr = 57,000 and another of Mr = 70,000. In
      isoelectrofocalization assays, the amidase behaved as an acidic protein.
      Ethylenediaminetetraacetate inhibited the enzyme activity; the Mg2+ requirement
      was confirmed. The simultaneous presence of sulfhydryl groups and disulfide bonds
      in the protein was evidenced by the inhibitions produced by different thiol
      blocking reagents and by several thiol-bearing substances. Direct measurements
      established the presence of two accessible thiol groups and the occurrence of
      nine disulfide bonds per protein molecule. Studies of substrate hydrolyzing
      capacities showed a marked preference for the muramoyl tripeptide derived from
      the Escherichia coli or Bacillus cereus mureins, the disaccharide tetrapeptide
      and the bis disaccharide tetra-tetrapeptide from E. coli were also good
      substrates. Activities on small muropeptides of other composition are also
      reported. Whole (insoluble) peptidoglycans representing the main bacterial
      chemotypes were submitted to the enzyme action; although with weak specific
      activities, the human amidase was nevertheless able to release soluble peptides
      from some of them. A bacteriolytic capacity on some microorganisms cannot be
      excluded. Results are discussed and the human enzyme is compared to presently
      known microbial muramoyl amidases.

PMID- 1974147
TI  - The kinetic mechanism of wild-type and mutant mouse dihydrofolate reductases.
AB  - A kinetic mechanism is presented for mouse dihydrofolate reductase that predicts
      all the steady-state parameters and full time-course kinetics. This mechanism was
      derived from association and dissociation rate constants and pre-steady-state
      transients by using stopped-flow fluorescence and absorbance measurements. The
      major features of this kinetic mechanism are as follows: (1) the two native
      enzyme conformers, E1 and E2, bind ligands with varying affinities although only
      one conformer, E1, can support catalysis in the forward direction, (2)
      tetrahydrofolate dissociation is the rate-limiting step under steady-state
      turnover at low pH, and (3) the pH-independent rate of hydride transfer from
      NADPH to dihydrofolate is fast (khyd = 9000 s-1) and favorable (Keq = 100). The
      overall mechanism is similar in form to the Escherichia coli kinetic scheme
      (Fierke et al., 1987), although several differences are observed: (1) substrates
      and products predominantly bind the same form of the E. coli enzyme, and (2) the
      hydride transfer rate from NADPH to either folate or dihydrofolate is
      considerably faster for the mouse enzyme. The role of Glu-30 (Asp-27 in E. coli)
      in mouse DHFR has also been examined by using site-directed mutagenesis as a
      potential source of these differences. While aspartic acid is strictly conserved
      in all bacterial DHFRs, glutamic acid is conserved in all known eucaryotes. The
      two major effects of substituting Asp for Glu-30 in the mouse enzyme are (1) a
      decreased rate of folate reduction and (2) an increased rate of hydride transfer
      from NADPH to dihydrofolate.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1974149
TI  - The role of the mature part of secretory proteins in translocation across the
      plasma membrane and in regulation of their synthesis in Escherichia coli.
AB  - Presently available data are reviewed which concern the role of the mature parts
      of secretory precursor proteins in translocation across the plasma membrane of
      Escherichia coli. The following conclusions can be drawn; i) signals, acting in a
      positive fashion and required for translocation do not appear to exist in the
      mature polypeptides; ii) a number of features have been identified which either
      affect the efficiency of translocation or cause export incompatibility. These
      are: alpha) protein folding prior to translocation; beta) restrictions regarding
      the structure of N-terminus; gamma) presence of lipophilic anchors; delta) too
      low a size of the precursor. Efficiency of translocation is also enhanced by
      binding of chaperonins (SecB, trigger factor, GroEL) to precursors. Binding sites
      for chaperonins appear to exist within the mature parts of the precursors but the
      nature of these sites has remained rather mysterious. Mutant periplasmic proteins
      with a block in release from the plasma membrane have been described, the
      mechanism of this block is not known. The mature parts of secretory proteins can
      also be involved in the regulation of their synthesis. It appears that exported
      proteins are already recognized as such before they are channelled into the
      export pathway and that their synthesis can be feed-back inhibited at the
      translational level.

PMID- 1974151
TI  - Benzodiazepines and catatonia.

PMID- 1974150
TI  - On remaining cytoplasmic.
AB  - The published literature contains a number of examples of normally non
      cytoplasmic proteins whose transport out of the cytoplasm is not completely
      abolished by drastic alterations to their routing signals (signal sequences,
      etc). Furthermore, there are numerous examples of cytoplasmic proteins that can
      be routed to and across plasma or organelle membranes by fusing them to routing
      signals. These 2 sets of observations lead to a re-evaluation of the reliability
      and accuracy of protein routing and to consideration of the consequences of the
      errors which might occur.

PMID- 1974152
TI  - Analysis of tandospirone (SM-3997) interactions with neurotransmitter receptor
      binding sites.
AB  - The interactions of tandospirone (formerly called SM-3997) with 5-HT and other
      neurotransmitter receptor binding sites were determined in brain homogenates.
      Tandospirone is most potent at the 5-HT1A receptor, displaying a Ki value of 27
      +/- 5 nM. The agent is approximately two to three orders of magnitude less potent
      at 5-HT2, 5-HT1C, alpha 1-adrenergic, alpha 2-adrenergic, and dopamine D1 and D2
      receptors (Ki values ranging from 1300 to 41000 nM). Tandospirone is essentially
      inactive at 5-HT1B receptors; 5-HT uptake sites; beta-adrenergic, muscarinic
      cholinergic, and benzodiazepine receptors. This pharmacological profile differs
      slightly from that of other novel anxiolytics such as buspirone, ipsapirone, and
      gepirone. Saturation and competition studies using 3H-tandospirone also suggest
      that the drug interacts with 5-HT1A receptor binding sites in rat cortical
      membranes (KD = 4.5 +/- 0.8 nM; Bmax = 2.2 +/- 0.6 pmol/g tissue). Based on
      adenylate cyclase studies which measure 5-HT1A receptor-mediated effects,
      tandospirone displays approximately 60% of the agonist effect of 8-OH-DPAT, a
      selective 5-HT1A agonist. Thus, the primary pharmacological effect of
      tandospirone appears to be partial agonism at the 5-HT1A receptor, an activity
      similar to other pyrimidinyl-piperazines which are being developed as novel
      anxiolytic agents.

PMID- 1974153
TI  - Sleep polygraphy in schizophrenia: methodological issues.
AB  - The findings of sleep studies in schizophrenia have remained inconsistent in the
      literature as exemplified by the recent controversy regarding reduced rapid eye
      movements (REM) latency in these patients. These inconsistencies can partly be
      explained by major methodological shortcomings in studies evaluating sleep in
      schizophrenia. Lack of standardized scoring and diagnostic methods in the earlier
      studies and more recently, the effect of neuroleptic treatment or its withdrawal,
      have confounded the sleep results. Data are presented to illustrate the effect of
      the presence of tardive dyskinesia or active psychotic symptoms that further skew
      the sleep polygraphic measurements in these patients. Studies in drug-naive
      patients can circumvent some of these confounds but then these studies are
      weakened by sampling bias. Available data suggest that previous duration of
      neuroleptic treatment, duration of neuroleptic withdrawal, presence of tardive
      dyskinesia, and severity of psychotic symptoms should be considered when
      interpreting REM sleep measures in schizophrenic patients.

PMID- 1974155
TI  - Origin of mutations in two families with X-linked chronic granulomatous disease.
AB  - The most common X-linked recessive form of chronic granulomatous disease (X-CGD)
      is characterized by the absence of cytochrome b558 in neutrophils. In a rare
      variant form of X-CGD, cytochrome b558 is present but not functional. The gene
      (locus symbol CYBB) was localized to band Xp21 by studies of patients with small
      chromosome deletions. The gene was cloned based on its location and found to
      encode the 91-Kd subunit of the cytochrome b558 complex. Most female carriers for
      X-CGD can be identified by their X-inactivation mosaicism; on average 50% of
      their neutrophils express the mutant phenotype and fail to reduce nitroblue
      tetrazolium (NBT). In 2 of 4 families studied, the maternal grandmothers had
      normal NBT tests, suggesting either nonrandom X-inactivation or new mutations.
      Restriction fragment length polymorphism analysis using closely linked flanking
      markers or the NsiI polymorphism detected by the CYBB probe itself, allowed us to
      identify the X chromosome carrying the mutation as derived from a healthy NBT
      positive maternal grandfather. The mothers of the affected boys must have
      received a paternal X chromosome carrying a new mutation, consistent with the
      maternal grandmothers' normal NBT tests. In all of eight potential carriers
      studied, the results of the NBT and DNA marker testing were in complete
      agreement. Prenatal diagnosis by DNA testing can be performed in early gestation
      obviating the need for fetal blood sampling.

PMID- 1974154
TI  - Increased blood clearance rate of indium-111 oxine-labeled autologous CD4+ blood
      cells in untreated patients with Hodgkin's disease.
AB  - Untreated patients with Hodgkin's disease (HD) have a blood T-lymphocytopenia
      mainly caused by a reduction of the CD4+ subset. Indirect support for a
      sequestration of T cells in the spleen and tumor-involved lymphoid tissue has
      accumulated. To test the hypothesis that the blood CD4 T-lymphocytopenia in
      patients with HD is caused by an altered lymphocyte traffic, 12 untreated HD
      patients and five in complete clinical remission (CCR) were studied. Blood
      lymphocytes were collected by leukapheresis and gradient centrifugation, and were
      further purified by an adherence step. The cells were labeled with indium-111
      oxine and reinfused intravenously into the patient. The radioactivity of CD4+ and
      CD8+ blood lymphocytes separated by immunoabsorption was measured from serial
      blood samples. CD4+ cells were eliminated more rapidly in untreated patients than
      patients in CCR. Repeated gamma camera imaging after autotransfusion of indium
      111 oxine labeled cells demonstrated an accumulation of radioactivity in tumor
      involved tissue of untreated patients. These findings support the concept of an
      enhanced elimination of CD4+ cells in patients with active HD that may contribute
      to the observed blood T-lymphocytopenia and may reflect a biologic response to
      the tumor.

PMID- 1974156
TI  - Fallacies and phobias about addiction and pain.
AB  - Research has indicated that approximately three-quarters of patients in acute
      care hospitals experience moderate to severe pain. It is thought that
      inadequately controlled pain is the result of poor clinical performance on the
      part of nurses and physicians. Faculty knowledge about pain mechanisms and
      pharmacology have been targeted as the source of their poor performance. In
      addition, practitioners may have fallacious beliefs about narcotics and pain.
      This study examined some of the misconceptions nurses have about addiction and
      pain management. A number of fallacies were identified. These included a very
      strong opiophobia or fallacy about addiction liability of narcotics even under
      conditions of normal hospital use.

PMID- 1974157
TI  - The 1990s: decade of the stimulants?
AB  - Does the media fan fake panics, forecast possible issues, create real problems,
      or detect problems at an earlier stage than treatment resources? A study of the
      relationship of tabloid news coverage of MDMA (Ecstasy) to drug treatment service
      demand found that treatment agencies were more concerned about amphetamine use
      but conversely tabloid coverage centred on ecstasy. Casual enquiries to a few
      drug agencies one year later discovered reports of increased numbers of clients
      presenting for ecstasy and reports of the drug's increased availability. The
      relationship between media coverage and changing drug availability and drug use
      is unclear. Short-term studies are unreliable, and interpretation of the
      relationship between drug use and media coverage runs a permanent risk of
      generating contradictory conclusions. The need for long-term serious study of the
      relationship between the media and drug use is stressed.

PMID- 1974158
TI  - Role of adrenoceptors in vitro and in vivo in the effects of lithium on blood
      glucose levels and insulin secretion in the rat.
AB  - 1. Pretreatment of rats with the non-selective alpha-adrenoceptor antagonist
      dihydroergotamine counteracts the inhibition of glucose-induced insulin secretion
      caused by lithium both in vitro and in vivo. The present study was therefore
      carried out to specify further which type of adrenoceptor is involved in lithium
      induced hyperglycaemia and inhibition of insulin secretion. 2. The lithium
      induced effects were reversibly blocked by pretreatment of rats with the alpha 2
      adrenoceptor antagonist yohimbine or a combination of yohimbine and the non
      selective beta-receptor antagonist propranolol, whereas the alpha 1-receptor
      antagonist prazosin and propranolol alone were ineffective in blocking these
      effects. 3. These findings suggest that the effects of lithium on plasma glucose
      and insulin levels are mediated mainly by the stimulation of alpha 2
      adrenoceptors.

PMID- 1974159
TI  - FPL 63012AR: a potent D1-receptor agonist.
AB  - 1. FPL 63012AR is a D1-receptor agonist in the dog kidney, 10 times as potent as
      dopamine, reducing renal vascular resistance by 20% with an intra-arterial dose
      of 0.42 nmol kg-1. 2. No prejunctional inhibitory D2-receptor agonist activity
      was detected in either the isolated ear artery of the rabbit or in the conscious
      dog as D2-receptor-mediated emesis. 3. Unlike dopamine, FPL 63012AR had no
      significant agonist activity at alpha 1-, alpha 2-, beta 1- or beta 2
      adrenoceptors. 4. FPL 63012AR is a potent inhibitor of [3H]-noradrenaline uptake
      (Uptake1) into brain synaptosomes, with an IC50 of 29.5 nM, i.e. 9.2 times more
      potent than dopamine. 5. The ability to block Uptake1, in the anaesthetised dog
      was confirmed by inhibition of the tyramine-induced pressor and inotropic
      responses. 6. Intravenous infusion of FPL 63012AR in anaesthetized and conscious
      dogs (0.3 to 3 nmol kg-1 min-1) reduced vascular resistance and increased blood
      flow to the kidney which was accompanied by hypotension and tachycardia. 7. It is
      concluded that FPL 63012AR is an example of a novel class of potent agonists at
      the D-receptor. Such compounds may have the potential for use clinically in
      improving renal perfusion and reducing afterload.

PMID- 1974160
TI  - Membrane hyperpolarization, cyclic nucleotide levels and relaxation in the guinea
      pig internal anal sphincter.
AB  - 1. Changes in membrane potential (measured with an intracellular microelectrode)
      and in cyclic nucleotide (adenosine 3':5'-cyclic monophosphate, cyclic AMP and
      guanosine 3':5'-cyclic monophosphate, cyclic GMP) levels (measured by
      radioimmunoassay) in response to inhibitory non-adrenergic non-cholinergic (NANC)
      field stimulation and drugs were investigated in the guinea-pig internal and anal
      sphincter (gpIAS) in the presence of phentolamine and atropine (each 10(-6) M).
      2. Inhibitory NANC nerve stimulation (single pulse, 5 pulses at 5, 10 and 20 Hz,
      0.5 ms supramaximal voltage) and adenosine triphosphate (ATP, 10(-7)-10(-3) M)
      inhibited spike discharge, hyperpolarized the membrane and relaxed the sphincter.
      The effects of inhibitory nerve stimulation were blocked by tetrodotoxin (TTX,
      10(-6) M) and, with those of ATP, were blocked by apamin (5 x 10(-6) M). 3.
      Isoprenaline (10(-9)-10(-4) M), cromakalim (10(-9)-10(-5) M), sodium
      nitroprusside (NaNP 10(-5) M), M&B 22948 (10(-4) M) and 8-bromocyclic GMP (8-Br
      cyclic GMP, 10(-4) M) also inhibited spike discharge, hyperpolarized the membrane
      and relaxed the sphincter. The effects of isoprenaline were blocked by
      propranolol (10(-6) M). However, forskolin (10(-9)-10(-7) M), M&B 22948 (10(-9)
      10(-5) M) and lower concentrations of NaNP (10(-9)-10(-6) M) relaxed the
      sphincter without affecting the membrane potential. 4. The characteristics of the
      membrane potential changes in response to different inhibitory stimuli in the
      gpIAS differed. Hyperpolarization produced by inhibitory NANC nerve stimulation
      and ATP were rapid in onset, of brief duration and of comparable amplitude.
      Isoprenaline and direct electrical stimulation also hyperpolarized the membrane
      and relaxed the muscle although the extent of the relaxation in these two cases
      was much less than that with nerve stimulation and ATP. In each case, the
      membrane potential change preceded relaxation and probably accounted for it. 5.
      Both inhibitory NANC nerve stimulation (80 pulses 8Hz supramaximal voltage 0.5
      ms) and ATP (10-aM) raised levels of cyclic GMP significantly and to a comparable
      degree and relaxed the sphincter. The effect of nerve stimulation was prevented
      by TTX (10- 6M) but not by apamin (5 x 10- 6M). Isoprenaline (10-s M), cromakalim
      (10 5 M) and forskolin (10 5M) were ineffective. 6. Inhibitory NANC nerve
      stimulation (80 pulses 8Hz 0.5ms supramaximal voltage) and ATP (10-4M) raised
      levels of cyclic AMP significantly to a comparable degree and relaxed the
      sphincter. The increase produced by nerve stimulation was abolished by TTX (10
      6M) and apamin (5 x 10-6M). Isoprenaline (10-4M), cromakalim (10-5 M) and
      forskolin (10-5 M) raised levels of this nucleotide significantly.

PMID- 1974161
TI  - Refractoriness of the gravid rat uterus to tocolytic and biochemical effects of
      atrial natriuretic peptide.
AB  - 1. Effects of atrial natriuretic peptide (ANP) on tension development,
      particulate guanylate cyclase activity and guanosine 3':5'-cyclic monophosphate
      (cyclic GMP) concentrations of uteri from oestrogen-treated, progesterone
      treated, ovariectomized and pregnant rats were determined in vitro. 2. ANP
      inhibited the tension development by myometrial tissues from oestrogen-treated
      virgin rats and the sterile horn of 10 to 14 day pregnant rats but not of the
      uterus from pregnant and progesterone-treated rats. 3. Inhibition of cyclo
      oxygenase and lipoxygenase activities did not restore the tocolytic activity of
      ANP on gravid uterus. ANP exerted a tocolytic effect on nongravid uterus
      submaximally stimulated by prostaglandin F2 alpha (PGF2 alpha), oxytocin,
      vasopressin, angiotensin II or 5-hydroxytryptamine (5-HT). 4. Ovariectomy
      decreased the tocolytic effects of ANP, which could be restored by oestrogen
      treatment. 5. The refractoriness to the tocolytic effect of ANP in pregnant rats
      was not accompanied by a decrease in its relaxant effects on isolated aortic
      strips. 6. Tocolytic effects of isoprenaline, isobutylmethyl xanthine and
      hydroxylamine were not influenced by pregnancy or progesterone treatment. Up to a
      concentration of 3 mM, sodium nitroprusside did not affect myometrial tension
      development. 7. Pregnancy and progesterone treatment markedly inhibited ANP
      induced increases in myometrial particulate guanylate cyclase activity and cyclic
      GMP concentrations but did not influence the effects of ANP on aortic cyclic GMP
      concentrations. 8. It is concluded that exposure of the myometrium to circulating
      and placentally-produced progesterone is responsible for the pregnancy-induced
      decrease in the effects of ANP on myometrial particulate guanylate cyclase
      activity and cyclic GMP concentrations and in turn on myometrial tension
      development.

PMID- 1974162
TI  - Association of osteoarthritis with homozygosity for a 5.8 kb Taq I fragment of
      the alpha 1-antichymotrypsin gene.
AB  - The genes coding for the protease inhibitors alpha 1-antitrypsin (A1AT) and alpha
      1-antichymotrypsin (A1ACT) were analysed by Southern blot in patients with
      rheumatoid arthritis, psoriatic arthritis, psoriasis without arthritis,
      polymyalgia rheumatica and generalized osteoarthritis. The probe/restriction
      enzyme combinations used were the 4.6 kb 5' fragment of the A1AT gene with the
      Sst I enzyme, the 6.5 kb 3' fragment of the same gene with Taq I and the 3.4 kb
      fragment of A1ACT with Taq I. The frequency of homozygous genotype for the 5.8 kb
      A1ACT band was increased in osteoarthritis (62.8% versus 36.8%, P = 0.01,
      relative risk = 2.9, aetiological fraction = 0.41). No other disease association
      was found with any marker. This suggests that the A1ACT gene may influence
      susceptibility to generalized osteoarthritis.

PMID- 1974163
TI  - Assessing combination therapy in rheumatoid arthritis: treatment with
      sulphasalazine and penicillamine.

PMID- 1974164
TI  - Striatal afferents in the newt Triturus cristatus.
AB  - In order to investigate the neuronal populations projecting to the corpus
      striatum in the brain of a urodele, Triturus cristatus, horseradish peroxidase
      (HRP) retrograde labeling was used in parallel with anterograde degeneration,
      glyoxylic acid histofluorescence and behavioral testing. Striatal injections of
      HRP revealed that the main striatal afferent systems originate within the
      diencephalon, specifically in the dorsal thalamus and paraventricular organ of
      the hypothalamus. Several small groups of neurons in other diencephalic areas
      also participate in striatal innervation: proeminentia ventralis, amygdala,
      contralateral corpus striatum, preoptic area, posterior tuberal nucleus, locus
      coeruleus and raphe nuclei. Degeneration experiments after mechanical lesion of
      the paraventricular organ established the existence of a hypothalamostriatal
      projection. Degenerating axonal profiles were also found in many of the
      structures already identified as projecting to the striatum, suggesting that the
      paraventricular organ might influence the striatum not only directly but also
      indirectly through these other afferent systems. In the paraventricular organ,
      glyoxylic acid fluorescence histochemistry showed numerous monoamine neurons that
      corresponded in distribution and morphology to the retrogradely HRP-labeled
      neurons. Paraventricular-organ-lesioned males displayed a severe impairment of
      courtship behavior in the form of decreased tail beating and head stepping by the
      females. This suggests that the regulation of stereotyped hypermotricity might
      involve the monoamine component of the hypothalamo-striatal projection.

PMID- 1974165
TI  - Nonprescription cough and cold remedies.

PMID- 1974166
TI  - Analysis of various mRNA potentially involved in cisplatin resistance of murine
      leukemia L1210 cells.
AB  - Enhanced DNA repair has been identified as a major mechanism of resistance to the
      anticancer drug cisplatin in murine leukemia L1210 cells. Studies of other cells
      have implicated the elevation of a variety of RNA transcripts in cisplatin
      resistance. This study investigated potential changes in transcription of these
      genes as well as genes involved in DNA repair. No elevation in any of the
      following transcripts was observed: thymidylate synthase, dihydrofolate
      reductase, DNA polymerase alpha, DNA polymerase beta, topoisomerase II, Ha-ras,
      beta-tubulin, metallothionein and the DNA repair genes ERCC1 and ERCC2. Thymidine
      kinase was increased no more than 2-fold. None of these RNA were induced by
      incubation with cisplatin. High levels of cisplatin produced selective decreases
      in certain RNA. These results demonstrate that the previous observations of
      elevated RNA can not be universally applied to all cisplatin-resistant cells.

PMID- 1974167
TI  - Short-term metabolic fate of L-[13N]glutamate in the Walker 256 carcinosarcoma in
      vivo.
AB  - In vivo studies with L-[13N]glutamate in the Walker 256 carcinosarcoma implanted
      under the renal capsule of female Sprague-Dawley rats demonstrate that uptake of
      glutamate and the rate of incorporation of the nitrogen label from this amino
      acid into metabolites is slower in the tumor than in nontumorous kidney tissue.
      Glutamate dehydrogenase, glutaminase, and alanine aminotransferase activities are
      significantly lower within the tumor than within the adjoining kidney. However,
      the tumor expresses high levels of aspartate aminotransferase, attesting to the
      importance of this enzyme in the metabolism of glutamate. Indeed, high
      performance liquid chromatographic analysis showed that the principal metabolic
      fate of label derived from L-[13N]glutamate in the tumor is incorporation into
      aspartate. Measurement of specific activity ratios of glutamate to aspartate
      shows that the transfer of nitrogen from glutamate to aspartate is rapid and that
      equilibration of label among components of the aspartate aminotransferase
      reaction is attained within minutes after tumor uptake. Analyses of the
      nontumorous portion of the implanted kidney also showed that aspartate is the
      major recipient of glutamate nitrogen. However, high performance liquid
      chromatographic analyses of deproteinized tissue revealed that glutamine and
      ammonia are also significant 13N-labeled metabolites formed from L-[13N]glutamate
      within the kidney. Proportionately lower amounts of these labeled metabolites
      were found in the tumor.

PMID- 1974168
TI  - p185neu expression in human lung adenocarcinomas predicts shortened survival.
AB  - p185neu is the protein product of the HER2/neu protooncogene. This protein has
      characteristics of a tyrosine kinase growth factor receptor and is postulated to
      be important in human carcinogenesis. To define the significance of the
      expression of this protein in human non-small cell lung cancer, 55 tumors from
      patients with squamous cell carcinoma (16), adenocarcinoma (29), or large cell
      carcinoma (10) of the lung were examined for p185neu using immunohistological
      methods. Five of 16 squamous cell carcinomas and 10 of 29 adenocarcinomas were
      found to overexpress p185neu relative to levels of expression seen in uninvolved
      bronchiolar epithelium. For the adenocarcinomas, p185neu expression was
      associated with older age (66.6 +/- 10.1 versus 57.5 +/- 10.8 years) (P = 0.04)
      and shortened survival (83.7 +/- 94.1 versus 188.5 +/- 120 weeks) (P = 0.01). In
      this group, using Cox's multivariate survival analysis, p185neu expression was
      found to be a significant determinant of survival (P = 0.04) even after
      accounting for the effect of tumor stage. For the squamous cell carcinomas,
      p185neu expression was not correlated with any of our clinicopathological
      parameters. Our findings indicate that non-small cell lung cancers which express
      p185neu do so at levels higher than that found in normal bronchiolar epithelium,
      and expression in adenocarcinomas of the lung is independently associated with
      diminished survival intervals.

PMID- 1974169
TI  - Drug-resistance phenomena in major psychoses: their discrimination and causal
      mechanisms.
AB  - Drug-resistance phenomena are commonly encountered in psychiatric practice and
      are of particular concern in the treatment of major psychoses. Of paramount
      importance is the need to discriminate between drug-resistance problems due to
      pharmacodynamic factors (i.e., receptor sensitivity) or pharmacokinetic factors
      (inadequate plasma concentration of the drugs at receptor sites). To exclude the
      former, plasma level measurements of antidepressant and neuroleptic compounds are
      desirable. Actually, lack of or poor compliance is a peculiarity (often
      underestimated) when treating psychotic patients, and the use of the drug plasma
      level/dose ratio (L/D) approach is useful, particularly with outpatients. Another
      source of drug resistance stems from the inter-individual metabolic variability,
      as with haloperidol or anticholinergic drugs, which are used to counteract
      neuroleptic-induced extrapyramidal side effects. In general, plasma-level
      measurement is advisable whenever no or poor response is obtained during standard
      treatments with neuroleptic, antidepressant, or anticholinergic drugs. Finally,
      this author suggests a four-level discrimination process to determine drug
      resistance in major psychoses, which includes clinical, pharmacological,
      pharmacokinetic, and pharmacodynamic factors.

PMID- 1974170
TI  - Effects of gamma-oryzanol on serum lipids and apolipoproteins in dyslipidemic
      schizophrenics receiving major tranquilizers.
AB  - The subjects were 20 chronic schizophrenic patients with dyslipidemia (total
      cholesterol levels greater than or equal to 220 mg/dl, triglycerides greater than
      or equal to 150 mg/dl, or high-density lipoprotein cholesterol less than or equal
      to 40 mg/dl) who had been receiving neuroleptics for a mean of ten years. Each
      patient was given 100 mg of gamma-oryzanol three times daily for 16 weeks. Total
      cholesterol and low-density lipoprotein cholesterol levels, respectively,
      decreased significantly, from 204 and 124 mg/dl at baseline to 176 and 101 mg/dl
      at week 12. High-density lipoprotein cholesterol levels were 36.1 mg/dl at
      baseline and 35.9 mg/dl at week 12. Apolipoprotein (apo) B levels decreased
      significantly from 116 mg/dl to 101 mg/dl at week 16; apo A-II levels increased
      significantly from 31.7 mg/dl to 34.7 mg/dl; and the apo B/apo A-I ratio declined
      significantly from 0.99 to 0.84. No treatment side effects were recorded. It is
      concluded that gamma-oryzanol is safe and effective in the treatment of
      dyslipidemia.

PMID- 1974171
TI  - Antihistamines.

PMID- 1974172
TI  - High levels of de novo methylation and altered chromatin structure at CpG islands
      in cell lines.
AB  - CpG islands are normally methylation free in cells of the animal, even when the
      associated gene is transcriptionally silent. In mouse NIH 3T3 and L cells,
      however, over half of the islands are heavily methylated. Near identity of the
      methylated subset in the two cell lines suggested that methylation is confined to
      genes that are nonessential in culture. In agreement with this, islands at
      several tissue-specific genes, but not at housekeeping genes, have become
      methylated in many human and mouse cell lines. At the chromatin level, methylated
      islands are Mspl resistant compared with their nonmethylated counterparts. We
      suggest that mutation-like gene inactivation due to CpG island methylation is
      widespread in many cell lines and could explain the loss of cell type-specific
      functions in culture.

PMID- 1974173
TI  - [Effects of Ligusticum wallichii on the plasma and CSF levels of dynorphin A1-13
      in rabbits under acute experimental cerebral ischemia].
AB  - By occluding the bilateral carotid arteries of rabbits to produce bilateral
      partial cerebral ischemia, and by using radioimmunoassays to measure the levels
      of dynorphin A1-13 like immunoreactivity (ir-Dyn A1-13) in plasma and
      cerebrospinal fluid (CSF), the authors find that the levels of ir-Dyn A1-13 in
      plasma and CSF have significantly increased (P less than 0.01) after cerebral
      ischemia appears. The result of the Ligusticum wallichii Franch (Ligusticum)
      pretreatment to the test-group shows a definite improvement of the changes of ir
      Dyn A1-13 levels in plasma and CSF. The severity of brain ischemic damage and
      neurologic dysfunction in Ligusticum-treated animals is lighter than that of
      saline-treated group, too. In this study, some new approaches are explored to
      explain the pathophysiology of cerebral ischemia and the mechanisms by which
      Ligusticum prevents and treats cerebral ischemia.

PMID- 1974174
TI  - Autoantibodies against peripheral blood cells appear early in HIV infection and
      their prevalence increases with disease progression.
AB  - The presence of platelet- and neutrophil-bound immunoglobulin (PBIg and NBIg) in
      thrombocytopenic or neutropenic HIV-infected individuals has led to the concept
      that in HIV infection thrombocytopenia and neutropenia are mediated by
      autoimmunity. However, PBIg and NBIg were also demonstrated in non-cytopenic HIV
      infected individuals. We determined the prevalence of autoantibodies against
      neutrophils and platelets by immunofluorescence in randomly chosen persons in
      different stages of asymptomatic and symptomatic HIV infection. Platelet and
      neutrophil autoantibodies already appeared in the asymptomatic stage and their
      prevalence further increased in the symptomatic stages. No correlation was found
      between the presence of either platelet or neutrophil antibodies and the
      occurrence of circulating immune complexes in the blood or the serum
      immunoglobulin level. There was no significant difference in neutrophil counts in
      HIV-infected persons with or without neutrophil autoantibodies. In addition, no
      significant difference in neutrophil count was found between HIV-infected and non
      HIV-infected persons. HIV-infected individuals with platelet autoantibodies
      tended to have a lower platelet count than HIV-infected individuals without these
      antibodies. However, the platelet count in HIV-infected individuals without
      platelet antibodies was significantly lower than in the non-HIV infected persons.
      Thus, autoantibodies against platelets and neutrophils occur early in HIV
      infection and their prevalence is correlated with disease progression. Their
      presence is associated with cytopenia only in a limited number of persons. Non
      immune mechanisms also mediate thrombocytopenia in HIV infection.

PMID- 1974175
TI  - Lymphocyte populations in autopsy bone marrow sections from recipients of
      allogeneic marrow and non-transplant sudden death cases.
AB  - Femoral marrow, obtained at autopsy, was stained using immunohistological
      techniques, for T (CD2+) cells, B (CD19+) cells, helper/inducer (CD4+) T cells,
      suppressor/cytotoxic (CD8+) T cells and natural killer (HNK1+) cells. The numbers
      present in 13 recipients of allogeneic marrow, 14 to 140 days after
      transplantation, were compared with those in marrows from nine subjects with no
      haematological or malignant conditions. In marrow sections from non-transplant
      subjects, approximately 8% nucleated cells were CD2+ with CD4+ and CD8+ cells
      present in nearly equal numbers; 1-3% were CD19+ and generally less than 1%
      HNK1+. The percentages of CD19+ and CD4+ cells were significantly reduced after
      bone marrow transplantation but, if a correction factor for marrow cellularity
      was introduced, then CD2+ and CD8+ cell values were also low. The findings were
      compared with the number of cells transplanted, the time after transplantation,
      presence of graft-versus-host disease or infection and peripheral blood white
      cell count, but no correlation was found.

PMID- 1974176
TI  - Cytokine regulation of intercellular adhesion molecule-1 (ICAM-1) expression on
      human glioblastoma cells.
AB  - Intercellular adhesion molecule-1 (ICAM-1) has recently been identified as one of
      the ligands for lymphocyte function-associated antigen-1 (LFA-1).
      Immunohistochemical staining of frozen tissue sections using the ICAM-1 antibody
      RR1/1 demonstrated significant levels of ICAM-1 expression on human glioblastoma
      cells and on intratumoural vascular endothelial cells. ICAM-1 was weakly
      expressed or absent from low grade gliomas and absent from normal and fetal
      brain. ICAM-1 expression was similar to that of MHC class II. HLA-DR antigens.
      Glioblastoma cell lines constitutively expressed ICAM-1 to a minimal or moderate
      extent. Surface antigen expression of ICAM-1 and ICAM-1-specific mRNA could be
      significantly increased by incubating glioblastoma cells with interleukin-1 beta
      (IL-1 beta), tumour necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN
      gamma). IL-2, IL-4, IL-6 and transforming growth factor beta 2 (TGF-beta 2) had
      no significant effect on surface antigen expression. Significant enhancement of
      ICAM-1 expression was obtained using TNF-alpha and IL-1 beta at 1-10 U/ml and at
      500 U/ml of IFN-gamma. Induction of ICAM-1 specific mRNA was observed 4 h after
      cytokine treatment and decreased by 24 h. Surface antigen expression of ICAM-1
      increased for up to 48 h after treatment.

PMID- 1974177
TI  - Relationships between 2H4 (CD45RA) and UCHL1 (CD45RO) expression by normal blood
      CD4+CD8-, CD4-CD8+, CD4-CD8dim+, CD3+CD4-CD8- and CD3-CD4-CD8- lymphocytes.
AB  - We characterized and established relationships between the expression of membrane
      2H4 (CD45RA) and UCHL1 (CD45RO) by enriched lymphocyte fractions prepared by
      selective immunomagnetic depletion of monoclonal antibody-defined populations.
      Cell fractions analysed in this study could be divided into two broad groups
      according to the presence (CD3+CD4+CD8-, CD3+CD4-CD8+, CD3+CD4-CD8dim+ and
      CD3+CD4-CD8-) or absence (CD3-CD4-CD8dim+ and CD3-CD4-CD8-) of the CD3 antigen.
      Preliminary studies confirmed a reciprocal relationship for CD45RA and CD45RO
      expression by major lymphoid components and further showed that the level or
      intensity of membrane 2H4 staining (2H4+, 2H4int and 2H4-) could be directly
      related to UCHL1 expression. As a reflection of their differential functions, the
      various CD3+ populations examined showed much greater heterogeneity in 2H4 and
      UCHL1 expression. CD3+CD4+CD8- cells generally showed significant proportions of
      2H4+, 2H4int and 2H4- components, whereas the CD3+CD4-CD8+ population was
      characterized by a predominance of 2H4+ cells. The results of this current
      investigation further suggested a higher proportion of dual-positive (2H4+UCHL1+)
      cells and a much greater degree of inter-individual variation than previously
      suspected. In contrast to CD3+ lymphocytes, natural killer (NK) associated CD3
      CD4-CD8dim+ and CD3-CD4-CD8- populations were mostly 2H4+ with only minor 2H4int
      components and very low expression of UCHL1. An additional observation of note
      was that the proportions of 2H4+ and 2H4- cells comprising the CD4+CD8- fraction
      in any given individual was highly correlated (P = 0.002) with the distributions
      of 2H4+ and 2H4- components within the CD4-CD8+ fraction. This suggests the
      possible existence of a common control mechanism for the acquisition of
      immunological memory by distinct lymphocyte populations and further indicates
      that individual variations in the distribution of 2H4/UCHL1 lymphocyte
      subpopulations may be a direct consequence of 'immunological experience' rather
      than age alone.

PMID- 1974179
TI  - Impaired in vitro survival of monocytes from patients with HIV infection.
AB  - In vitro survival of monocytes (MO) was studied in 59 patients with HIV infection
      of different clinical stages. MO from 61 donors and 12 healthy seronegative
      homosexual men were also examined. Compared with the number of MO seeded, the
      percentage of adherent monocyte-derived macrophages (MDM) present after 10 days
      was significantly lower in patients with HIV infection than in the controls.
      However, the number of viable, non-adherent MO/MDM was similar in patients and
      controls. Our data indicate markedly decreased in vitro survival of MO from
      patients with HIV infection. After 10 days, the MDM population in the patient
      cultures was significantly less differentiated than the control cells, assessed
      by immunocytochemical staining with monoclonal antibodies against differentiation
      antigens. Reduced in vitro survival of MO/MDM was associated with low numbers of
      CD4+ and CD8+ lymphocytes in blood, reduced lymphocyte mitogen responses,
      presence of HIV p24 antigen in serum and advanced clinical stage. Decreased in
      vitro survival of MO/MDM may be associated with HIV replication in the cells.
      Although the level of HIV replication in the cultures was low as assessed by
      measurement of HIV p24 antigen in culture supernatants and staining of MO/MDM for
      HIV antigens, cytopathogenic effects of HIV or HIV products cannot be ruled out.

PMID- 1974178
TI  - Autoreactive cytotoxicity in HIV-infected individuals.
AB  - A possible role for autoimmunity in the pathogenesis of HIV infection has been
      suggested, based upon the certain degree of homology shared by HIV gp41 and MHC
      class II molecules. A number of humoral markers of autoimmunity have since been
      found in seropositive subjects. We have evaluated the cellular autoreactive
      response in HIV-infected individuals. Our study demonstrates the existence of a
      cytolytic activity, present in seropositive but not in seronegative subjects.
      This activity is mediated by CD3+ T cells, which only occasionally express the
      CD8 or the CD4 surface markers. Effector cells do not appear to exert their
      activity in a MHC-restricted fashion, since allogeneic target cells could also be
      killed, recovered from allogeneic seropositive as well as from seronegative
      subjects. Several types of target cells were lysed: T cell blasts and Epstein
      Barr virus (EBV) transformed B cells, suggesting that the target antigen is
      common to at least these two cell types. The fact that cells from seronegative
      individuals were lysed argues against the recognition of an HIV-specific antigen.
      The nature of the target determinants and the identity of the effector cells are
      discussed.

PMID- 1974180
TI  - Surface immunoglobulin-positive T lymphocytes in HIV-1 infection: relationship to
      CD4+ lymphocyte depletion.
AB  - T lymphocytes bound to autologous immunoglobulin (surface Ig + T cells) and serum
      antibodies that bind to allogeneic lymphocytes have been detected in HIV-1
      infected individuals, but their significance in the immunopathogenesis of HIV-1
      infection is uncertain. We tested peripheral blood from HIV-1-infected
      individuals to determine if surface Ig+ T cells are specific for HIV-1 infection
      and are associated with CD4+ lymphocyte depletion. The majority of HIV-1-infected
      individuals contained substantial numbers of circulating surface Ig+ T cells. The
      presence of such cells was restricted to seropositive individuals and not related
      to risk factors associated with the acquisition of HIV-1 infection. Autologous
      immunoglobulin was detected on both CD4+ and CD8+ cells in all patients tested.
      Most individuals with surface Ig+ T lymphocytes also had serum anti-T-lymphocyte
      antibodies. The presence of surface Ig+ T lymphocytes correlated significantly
      with lower absolute CD4+ lymphocyte counts only in asymptomatic, HIV-1-infected
      individuals.

PMID- 1974181
TI  - Activation antigens expressed on T-cells of the peripheral blood in Sjogren's
      syndrome and rheumatoid arthritis.
AB  - We analyzed activated T-cells in the peripheral blood (PB) of 29 patients with
      Sjogren's syndrome (SS: 13 I degrees-SS and 16 II degrees-SS patients) and 11
      patients with rheumatoid arthritis (RA) by two-color flowcytometry using
      antibodies to antigens serially expressed on the cell surface after activation-
      interleukin-2 receptor (IL-2R), HLA-DR, T-lineage specific antigen (TLiSA-1) and
      very late antigen (VLA-1). The early and intermediate activation antigens, DR and
      TLiSA-1, were significantly increased in the PB of SS and/or RA patients. The
      proportions of activated T-cells were higher in CD8+ cells than those in CD4+
      cells. T-cells expressing IL-2R or VLA-1, which appear in the very early or late
      stages of activation, were also increased in SS and/or RA patients. The results
      suggest that activated T-cells in the PB of both diseases might be recruited from
      continuously activated lymphoid organs, and that the activated cells migrate from
      PB into target tissues. In addition, the increase of activated T-cells in PB
      might be one of the causes of the deficient cell-mediated immunity reported in
      these patients.

PMID- 1974182
TI  - Clinical pharmacokinetics of drugs used in the treatment of gastrointestinal
      diseases (Part I).
AB  - Drug treatment of gastrointestinal diseases, which was previously limited to the
      use of antacids, anticholinergics, antispasmodics, cathartics and laxatives, has
      changed markedly over the past decade. Histamine H2-receptor antagonists (e.g.
      cimetidine, ranitidine and more recently famotidine and nizatidine) have
      revolutionised the treatment of peptic acid disorders, but their role is
      currently challenged by muscarinic-M1-receptor antagonists (e.g. pirenzepine),
      proton pump inhibitors (e.g. omeprazole), prostaglandin analogues and site
      protective drugs (e.g. colloidal bismuth subcitrate and sucralfate). Newer
      antiemetics with prokinetic properties (e.g. metoclopramide, domperidone and
      cisapride) have also been introduced in the management of gastrointestinal
      motility disturbances, and new anti-inflammatory salicylates (e.g. olsalazine and
      mesalazine) have been developed for the treatment of chronic inflammatory bowel
      diseases. Finally, diphenoxylate and loperamide have gained wide clinical
      application as nonspecific antidiarrhoeal agents. The basic pharmacokinetic
      properties of the above agents are briefly reviewed with the main emphasis on the
      newer and more important drugs in current use. Furthermore, the effects of age
      and disease on pharmacokinetics, in addition to drug interaction potentials and
      pharmacokinetic-pharmacodynamic relationships, are discussed. The anti
      inflammatory salicylates, nonspecific antidiarrhoeal agents, laxatives and
      cathartics will be dealt with in Part II.

PMID- 1974183
TI  - [T-lymphocyte subsets in peripheral blood of patients with bone tumors].
AB  - Peripheral blood T-cell subsets of 54 patients with malignant or benign bone and
      soft tissue tumors and 20 age-and sex-matched normal controls were studied by
      using monoclonal antibodies. T-cell subsets were also studied before and after
      operation in ten patients with osteosarcoma. The number of T cells (OKT 11) and
      OKT 4 cells significantly decreased in malignant bone and soft tissue tumors. The
      number of OKT 8 cells increased. Statistically significant decrease in the T4/T8
      ratio and the number of macrophage were also found in malignant bone and soft
      tissue tumors. In giant cell tumor of bone, the number of T cells and OKT 4 cells
      were also statistically decreased. But, the number of OKT 8 cells and macrophage
      remained unchanged. The ratio of T 4/T 8 was nearly normal. There was no
      difference in T cell subsets between benign bone tumors and normal controls. In
      malignant bone tumors, the number of T cells and T 4/T 8 ratio in some degree may
      be as a predictor for prognosis.

PMID- 1974184
TI  - The role of sulfate conjugation in the elimination kinetics of diflunisal in the
      rat.

PMID- 1974185
TI  - The effect of hepatic blood flow on formation of metabolites.

PMID- 1974186
TI  - Ethyl carbamate metabolism: in vivo inhibitors and in vitro enzymatic systems.
AB  - The metabolism of ethyl carbamate and the localization of its metabolites have
      been shown to be almost completely inhibited by ethanol in the mouse [Waddell,
      Marlowe, Pierce: Food Chem. Toxicol.25, 527 (1987); Yamamoto, Pierce, Hurst,
      Chen, Waddell: Drug Metab. Dispos. 16, 355 (1988)]. The enzyme system catalyzing
      this metabolism which is inhibited by ethanol now has been further investigated
      in both in vivo and in vitro studies. There is a direct, highly significant
      relationship between the extent of metabolism of ethyl carbamate and covalent
      binding of metabolites to liver protein. Paraoxon, carbaryl, CCl4 ethanol,
      methimazole, 4-methylpyrazole, diethyl maleate, ethyl N-hydroxycarbamate, and t
      butyl carbamate inhibit, to different extents, the metabolism of ethyl carbamate
      in vivo; SKF-525A, CoCl2, Cacyanamide, chloral hydrate, 2-oxo-4-thiazolidine
      carboxylic acid, allopurinol, and methyl carbamate do not. Porcine liver
      esterase, yeast aldehyde dehydrogenase and mouse liver catalase catalyzed the
      metabolism in vitro; dog or bovine catalase, acid phosphatase, alcohol
      dehydrogenase, or carbonic anhydrase did not under the conditions tested.
      Paraoxon, 4-methylpyrazole, carbaryl, and NaF significantly inhibited the
      hydrolytic activity of mouse liver homogenates toward p-nitrophenyl acetate;
      ethanol or ethyl carbamate did not. However, each of these, except 4
      methylpyrazole, inhibited the metabolism of ethyl carbamate by mouse liver
      homogenate or porcine liver esterase to about the same extent. Ion exchange
      chromatography of mouse liver cytosol revealed that the fraction with ability to
      metabolize ethyl carbamate co-chromatographed almost exactly with the ability to
      hydrolyze p-nitrophenyl acetate. It is proposed that ethyl carbamate is
      metabolized in the mouse, at least partially, by esterases; however, metabolism
      by other enzyme systems cannot be excluded.

PMID- 1974187
TI  - Pharmacokinetics and disposition of WR-1065 in the rhesus monkey.
AB  - The pharmacokinetics of WR-1065 [S-2-(3-aminopropylamino)ethanethiol] were
      investigated following iv, intraduodenal, and intraportal administrations in the
      rhesus monkey. Pharmacokinetic parameters were estimated by compartmental
      modeling of plasma concentration data from 10-min and 120-min iv infusions.
      Higher apparent volumes of distribution (Vc and Vss) and higher mean residence
      time (MRT) were observed at the slower infusion rate but a constant total dose.
      The values reflect a change in the distribution of WR-1065, possibly due to to
      saturation of binding in plasma and tissue. However, clearance remained
      unchanged. For a monkey administered approximately twice the 60 mg/kg dose
      infused over 120 min, data analysis indicates a disproportional increase in AUC
      and a substantial decrease in clearance. Low and erratic plasma concentrations of
      free drug (analytically determined without reductive cleavage) were observed
      following intraduodenal administration of WR-1065, demonstrating the drug's poor
      oral bioavailability. Results of intraduodenal administrations of radiolabeled
      drug indicated than an appreciable amount of the radiolabel in the dose reached
      the systemic circulation. However, after either intraduodenal or iv
      administration, only 31% of the AUC (radiolabel) could be accounted for as total
      (free and disulfide-bound) WR-1065 by specific analysis in separate experiments.
      Low levels of total cysteamine strongly suggest it to be a minor contributor to
      the disposition of the drug. Free WR-1065 AUC values following intraportal
      administration were similar to values obtained after iv administration.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1974188
TI  - Nitroglycerin metabolism in subcellular fractions of rabbit liver. Dose
      dependency of glyceryl dinitrate formation and possible involvement of multiple
      isozymes of glutathione S-transferases.
AB  - The hepatic transformation of glyceryl trinitrate (GTN), commonly known as
      nitroglycerin, was studied in subcellular fractions prepared from rabbit livers.
      Both the cytosolic and microsomal fractions show activity toward GTN metabolism.
      Moreover, the formation of glyceryl dinitrates (GDNs) seems to be governed by
      different enzymatic processes in the two fractions. 1,2-GDN was preferentially
      formed in cytosolic fractions, whereas in microsomal fractions, 1,3-GDN was the
      predominant product. In cytosolic fractions, increasing starting concentrations
      of GTN led to a decrease in both the GTN degradation rate and the GDN ratio (1,2
      GDN/1,3-GDN), which was mainly accounted for by saturation of the 1,2-GDN
      formation pathway. Various glutathione S-transferase (GST) inhibitors affected
      the rate of GDN formation differentially. In cytosolic fractions, 1-chloro-2,4
      dinitrobenzene and iodomethane caused no change in the GDN ratio, while
      sulfobromophthalein, ethacrynic acid, and p-nitrobenzyl chloride decreased the
      GDN ratio, suggesting that different GST isozymes are inhibited by these agents.
      In microsomal fractions, no dose-dependent GTN metabolism and related change in
      the GDN ratios could be observed. With the exception of ethacrynic acid, addition
      of GST inhibitors did not decrease GDN metabolite production, and even in this
      case, no change in the GDN ratio was observed. The results suggest that different
      GTN metabolic pathways are present in the liver, most likely involving different
      GST isozymes.

PMID- 1974189
TI  - Inhibition and induction of theophylline metabolism by 8-methoxypsoralen. In vivo
      study in rats and humans.
AB  - The effects of 8-methoxypsoralen (8-MOP) on the metabolism of theophylline were
      studied in rats and humans. Rats were randomized into three groups and prepared
      with iv jugular catheters. Group I (N = 4) received a single ip injection of 27
      mg/kg of 8-MOP, group II (N = 5) vehicle (corn oil), and group III (N = 4) 50
      mg/kg/day of 8-MOP for 3 days. Rats were subsequently administered 15 mg/kg of
      theophylline iv, and timed blood samples (0.2 ml) were assayed for theophylline
      by HPLC. Theophylline clearance (ml/min/kg; mean +/- SD) was 1.7 +/- 0.3, 2.4 +/-
      0.5, and 9.5 +/- 1.6 in groups I, II, and III, respectively. The half-life
      (harmonic mean) from 0.5 to 12 hr was 7.2, 3.6, and 0.8 hr. Urinary excretion of
      unchanged theophylline (mean +/- SD) from 0 to 24 hr was 60 +/- 10, 41 +/- 6, and
      13 +/- 3% of the administered dose. In a crossover study, three healthy, male,
      nonsmokers received 600 mg of oral theophylline. Urine and plasma were collected
      for 48 hr. One week later, subjects received 1.2 mg/kg of oral 8-MOP followed in
      1 hr by 600 mg of oral theophylline. Mean residence time of theophylline
      increased from 10.7, 17.2, and 12.2 hr in the control period, to 20.3, 19.0, and
      18.4 hr after 8-MOP. The AUC (microgram.hr/ml) of theophylline increased from
      204, 213, and 204, to 555, 364, and 432, while clearance (ml/min/kg) decreased
      from 0.74, 0.57 and 0.63, to 0.27, 0.33, and 0.30, respectively. Urinary
      excretion of unchanged theophylline from 0 to 48 hr increased from 14, 14, and
      15, to 24, 21, and 20%. We conclude that 8-MOP administered acutely is a potent
      inhibitor of theophylline metabolism and chronically in the rat is a powerful
      inducer.

PMID- 1974190
TI  - Bromobenzene metabolism in vivo and in vitro. The mechanism of 4-bromocatechol
      formation.
AB  - The metabolism of bromobenzene has been examined in isolated hepatocytes and
      liver microsomes from phenobarbital-induced rats and in phenobarbital-induced
      rats in vivo. The metabolite profile produced upon incubation of isolated rat
      hepatocytes with bromobenzene differed with the hepatocyte concentration. At a
      low hepatocyte concentration (0.5 x 10(6) cells/ml), 4-bromophenol was the major
      metabolite, while at higher hepatocyte concentrations (2.0 and 5.0 x 10(6)
      cells/ml) bromobenzene-3,4-dihydrodiol was the major metabolite. 4-Bromophenol
      was the primary metabolite in incubations with rat liver microsomes. In vivo, 3-
      and 4-bromophenol were more predominant, with very little dihydrodiol formed. 4
      Bromocatechol, a potentially toxic metabolite of bromobenzene, was formed in vivo
      as well as in isolated hepatocytes and microsomes. However, the mechanism of
      catechol formation differed, as determined by the retention of a deuterium label
      at the para position of bromobenzene. In microsomes, 4-bromophenol was the
      predominant precursor metabolite of 4-bromocatechol. In isolated hepatocytes,
      although the relative contribution of 4-bromophenol as the bromocatechol
      precursor differed with hepatocyte concentration, bromobenzene-3,4-dihydrodiol
      was the predominant precursor at all concentrations. In vivo, as in isolated
      hepatocytes, 4-bromocatechol was formed primarily via bromobenzene-3,4
      dihydrodiol.

PMID- 1974191
TI  - Pathways of gallopamil metabolism. Regiochemistry and enantioselectivity of the O
      demethylation processes.
AB  - The oxidative O-demethylation of pseudoracemic gallopamil by rat and human liver
      microsomes was studied. By comparison of GC/MS retention times and fragmentation
      patterns with data from authentic standards, the four possible regioisomeric
      monophenolic metabolites, 2-(4-hydroxy-3,5-dimethoxyphenyl)-2-isopropyl-5-[(3,4-
      dimethoxyphenethyl)methylamino]-valeronitrile (2), 2-(5-hydroxy-3,4
      dimethoxyphenyl)-2-isopropyl-5-[(3,4-
      dimethoxyphenethyl)methylamino]valeronitrile (3), 2-(3,4,5-trimethoxyphenyl)-2
      isopropyl-5-[(4-hydroxy-3-methoxyphenethyl) -methylamino]valeronitrile (4), and 2
      (3,4,5-trimethoxyphenyl)-2-isopropyl-5-[(3-hydroxy-4-
      methoxyphenethyl)methylamino]valeronitrile (5), were characterized. Rat liver
      microsomal oxidation produced all four regioisomeric monophenols which accounted
      for only 10% of the oxidative metabolism, the remaining 90% being N-dealkylation
      metabolites. Preference for metabolism of the O-methyl ethers at p-positions on
      each of the aromatic ring systems was noted, with more O-demethylation of the O
      methyl ethers on the aromatic ring adjacent to the chiral center than on the
      aromatic ring in the short side chain. Significant enantio-selectivity was noted,
      the S/R ratios being 2.26, 1.97, 1.87 and 1.30 for formation of 2, 3, 4 and 5,
      respectively. Biliary excretion of the O-demethylated metabolites as conjugates,
      cleaved by beta-glucuronidase, was observed in rats after administration of
      pseudoracemic gallopamil. Significant stereoselectivity was noted, S/R ratios
      being 0.62, 1.61, 1.49 and 2.19 for 2, 3, 4 and 5, respectively. Human liver
      microsomal oxidation produced more p- than m-O-demethylation, with 4 less than 5,
      and 2 less than 3, but quantitatively the pathway is a minor one compared to N
      dealkylation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1974192
TI  - Tissue distribution and metabolic disposition of zidovudine in rats.
AB  - The tissue distribution and metabolic fate of [5'-3H]zidovudine was studied in
      rats after a single dose of 10 mg/kg by gavage. The drug was absorbed rapidly and
      distributed into all tissues. Peak blood and tissue levels were observed 0.25 hr
      post-dose. The level of peak radioactivity in the stomach, intestine, liver,
      spleen, adrenals, and kidney was higher than in plasma, while in the heart, lung,
      thymus, lymph nodes, muscle, bone, and skin it was similar to that in plasma.
      Only in the testes and the brain the radioactivity was lower than in plasma.
      Blood and plasma radioactivity levels were nearly equivalent. A biphasic
      disappearance of radioactive material was observed in blood and plasma, as well
      as in most tissues, with a rapid decline in the early phase (0.25-4 hr) and a
      slower decline thereafter. The 0-24-hr urinary and fecal recoveries (mean +/- SD)
      of radioactive material were 78 +/- 14% and 20 +/- 9% of dose, respectively,
      indicating virtually complete recovery of the radioactive dose. Reversed-phase
      HPLC analysis indicated that approximately 88% of urinary radioactivity
      corresponded to unchanged zidovudine, with the remaining radioactivity accounted
      for by five metabolites. One of these urinary metabolites was identified as 3'
      azido-3'-deoxy-5'-O-beta-D-glucopyranuronosylthymidine and another as 3'-amino-3'
      deoxythymidine (AMT). The majority of fecal radioactivity (greater than 70%)
      corresponded to AMT. There is a component of biliary excretion in the disposition
      of zidovudine. At least 7% of a parenteral dose of zidovudine was secreted in the
      bile, primarily as 3'-azido-3'-deoxy-5'-beta-D-glucuronylazidothymidine, which
      may be a source of fecal AMT.

PMID- 1974193
TI  - Isolation and characterization of an ether glucuronide of zidovudine, a major
      metabolite in monkeys and humans.
AB  - A major metabolite of zidovudine (3'-azido-3'-deoxythymidine, AZT), which
      previously had not been observed in a variety of experimental animals, was
      identified in samples of plasma and urine from cynomolgus monkeys and a patient
      treated with AZT. The urinary recoveries of metabolite from the monkeys and the
      patient were, respectively, 1.5- and 6.9-fold higher than the recoveries of
      unchanged drug. The metabolite was purified in gram quantities from the urines of
      the monkeys and the patient and was identified enzymatically, using beta
      glucuronidase and a specific inhibitor of the enzyme, as a glucuronide conjugate
      of AZT. The metabolite was formed in vitro by incubating AZT with preparations of
      human liver in the presence of UDP-glucuronic acid. In addition, the metabolite
      was prepared synthetically and physical characterizations--including
      microanalysis and UV, IR, NMR and mass spectra--of compound from all three
      sources were identical and confirmed the metabolite to be the 5'-O-beta-D
      glucuronide of AZT.

PMID- 1974194
TI  - Effect of growth hormone on caffeine metabolism in hypophysectomized rats.
AB  - Two groups of six male Sprague-Dawley hypophysectomized rats (operated on day 0),
      8 weeks old, treated by sc tetracosactid (ACTH, 10 micrograms every 24 hr),
      thyroxine (5 micrograms/100 g every 24 hr) and desmopressin (240 ng/kg/24 hr
      continuous infusion) received SC either saline (group I) or human growth hormone
      (hGH, 120 micrograms/24 hr) (group II) continuous infusion. ACTH and thyroxine
      were administered on days 7-19 and desmopressin and hGH on days 8-19, after
      surgery. They received po caffeine 4 mg/kg as citrate salt on day 15. The 0-12,
      12-24 and 24-48 hr urine samples were collected after caffeine administration.
      Caffeine and metabolites concentrations in urines were determined using HPLC.
      Effect on hGH on caffeine metabolism was assessed comparing group I and group II.
      In 0-48-hr urine, 1-methylxanthine (154 +/- 169 pmol/g) and 3-7-dimethyluric acid
      (5.57 +/- 19.3 pmol/g) in group II were significantly lower than in group I (391
      +/- 340 pmol/g and 262 +/- 338 nmol/g, respectively) (p less than 0.05). Other
      metabolites (6-amino-5-(N-methyl formylamino)-1,3-dimethyluracil included)
      excretion was not altered. Total, N3-, N7- and N1-demethylation ratios on 0-48 hr
      urine were not modified by hGH treatment. However, demethylation ratios on 12-24
      and 24-48 hr (N3 + N7 + N1) and on 24-48 hr urine samples (N3 and N7) were
      significantly reduced in group II (p less than 0.05) suggesting an increase in
      the rate of appearance of demethylated metabolites during hGH treatment.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1974195
TI  - Pathways of gallopamil metabolism. Regiochemistry and enantioselectivity of the N
      dealkylation processes.
AB  - The N-dealkylation pathway for the metabolism of pseudoracemic gallopamil was
      studied in the presence of rat and human liver microsomes and in vivo in rats and
      man. Metabolites were characterized by comparison of their GC/MS retention times
      and fragmentation patterns with those of authentic compounds. In the presence of
      rat liver microsomes, N-dealkylation accounted for about 90% of the observed
      oxidative metabolism, affording a 4:1 ratio of norgallopamil (2) and, N-methyl-N
      [2-methyl-3-cyano-3-(3,4,5-trimethoxyphenyl)-6-hexyl] amine (3), and about 1% of
      N-methyl-N-(3,4-dimethoxyphenethyl)amine (4). Secondary amines 2 and 3 arose
      enantioselectively from S-(-)-gallopamil, the S/R ratios being 1.36 and 1.71,
      respectively. The alcohols, 3,4-dimethoxyphenylethanol (6) and 2-methyl-3-cyano-3
      (3,4,5-trimethoxyphenyl)-6-hexanol (8), were formed from the respective
      intermediate aldehydes 5 and 7, probably non-enzymatically, under the reductive
      conditions (NADPH) of the microsomal incubations. Incubation of gallopamil with
      9,000g supernatant fraction of rat liver led to carboxylic acid metabolites
      arising from oxidative metabolism of the aldehydes. 3,4-Dimethoxyphenylacetic
      acid (12) and 4-(3,4,5-trimethoxyphenyl)-5-methyl-4-cyanohexanoic acid (11) were
      formed in a 3:5:1 ratio. In the presence of human liver microsomes, formation of
      2 also predominated over formation of 3, with alcohols 6 and 8 being produced as
      well. However, 4 was not observed. Consistently, the N-dealkylation process
      provided slightly more R than S products with the S/R ratio being 0.7-0.9 for
      metabolites 2, 3, 6, and 8. The amines formed from N-dealkylation were also
      observed as urinary metabolites in a human subject after a single oral dose of
      pseudoracemic gallopamil.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1974196
TI  - Pharmacokinetics of methysergide and its metabolite methylergometrine in the rat.
AB  - The pharmacokinetics of methysergide (MS) and its metabolite methylergometrine
      (MEM) was studied in male Sprague-Dawley rats. MS was administered iv in doses of
      0.71 (0.25 mg/kg) or 2.8 mumol/kg (1.0 mg/kg). The metabolite MEM was
      administered as iv doses of 0.74 (0.25 mg/kg) or 2.9 mumol/kg (1.0 mg/kg). The
      steady state characteristics of these compounds were also studied after constant
      rate iv infusion of MS at two different rates, 0.70 and 14.0 nmol/min per kg.
      Plasma protein binding and blood/plasma partitioning for MS were determined over
      a range of concentrations. Plasma and blood concentrations of MS and MEM were
      measured by HPLC with fluorescence detection. The plasma clearance of MS was high
      and ranged from 74.2-102 ml/min per kg. The two iv doses of MS were not
      equivalent after dose correction; clearance, volume of distribution at steady
      state and terminal half-life were significantly greater for the higher dose.
      Plasma clearance from the two iv infusions of MS were in accordance with that
      from the lower iv dose. Protein binding as well as the plasma/blood partitioning,
      of MS was constant over the range of concentrations observed in the disposition
      studies, averaging 84.2% and 1.67%, respectively. The metabolite MEM had a plasma
      clearance five to six times lower than that of the parent drug but a similar
      volume of distribution at steady state. The formation of MEM after MS
      administration was relatively low and appeared to be saturable since the
      formation clearance of MEM decreased significantly from 3.5 to 1.9 ml/min per kg
      for the low and the high rate of iv infusion of MS, respectively.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1974197
TI  - The hydrolysis activation of the doxorubicin cardioprotective agent ICRF-187 [+)
      1,2-bis(3,5-dioxopiperazinyl-1-yl)propane).
AB  - ICRF-187 [(+)-1,2-bis(3,5-dioxopiperazinyl-1-yl)propane] has shown promise
      [Speyer et al., N. Engl. J. Med. 319, 745 (1988)] as a cardioprotective agent
      against what may be an iron-based doxorubicin (Adriamycin)-induced
      cardiotoxicity. ICRF-187 likely exerts its action through its rings-opened
      hydrolysis product, a compound that has an EDTA-type structure and, likewise,
      strongly binds metal ions. The hydrolysis of ICRF-187 was followed
      spectrophotometrically in the ultraviolet and was shown to be pseudo-first-order
      over a wide pH range. The hydrolysis mechanism was shown to have a hydroxide
      catalyzed path and a pH-independent path similar to the hydrolysis of other
      imides. The anionic form of ICRF-187 (with a pKa of 9.6 at 37 degrees C) was
      resistant to hydroxide attack. The kinetically, spectroscopically and
      potentiometrically determined pKa values were all in excellent agreement and thus
      provided a test of the mechanism. Each imide group underwent hydrolysis and
      ionization independently of the other. The rate of ICRF-187 hydrolysis was also
      followed by observation of the removal of Cu2+ from a Cu2(+)-doxorubicin complex
      by the ICRF-187 hydrolysis product.

PMID- 1974198
TI  - Oxidative cleavage of the pentyl side-chain of cannabinoids. Identification of
      new biotransformation pathways in the metabolism of 4'-hydroxy-delta-9
      tetrahydrocannabinol in the mouse.
AB  - During an investigation of the mechanisms leading to the formation of metabolites
      of cannabinoids in which the pentyl side chain is reduced to 2, 3 or 4 carbon
      atoms, the further metabolism of 4'-hydroxy-delta 9-tetrahydrocannabinol was
      investigated in vivo in mice. Metabolites were extracted with ethyl acetate,
      concentrated by chromatography on Sephadex LH-20 and identified by GC/MS. Ten
      metabolites were identified and a further two had tentative structural
      assignments made. The major metabolic route, in common with that seen with most
      cannabinoids, was hydroxylation at the allylic 11-position, followed by oxidation
      to a carboxylic acid. Additional hydroxylation occurred at C-8. Abundant
      metabolites were also formed by oxidative cleavage of the pentyl side chain. The
      major metabolites of this type had lost the terminal two carbon atoms to give
      compounds containing a carboxyethyl side chain. This is the major product
      normally produced by beta-oxidation of the acid formed from 5'-hydroxy-delta 9
      tetrahydrocannabinol. Trace concentrations of two other acids that appeared to
      have a carboxypropyl side chain were also found. The results show that, in
      addition to beta-oxidation, initiated by hydroxylation at the 5'-carbon atom
      (omega-hydroxylation), at least one other oxidative route, initiated by omega-1
      hydroxylation, is involved in the production of metabolites with two carbon atoms
      missing from the pentyl side chain. This pathway does not seem to have been
      characterized as a biotransformation mechanism in drug metabolism and a possible
      mechanism is suggested.

PMID- 1974199
TI  - Tolbutamide hydroxylation by human, rabbit and rat liver microsomes and by
      purified forms of cytochrome P-450.
AB  - Tolbutamide hydroxylation has been investigated in human, rabbit and rat liver
      microsomes and by six purified forms of hepatic rabbit cytochromes P-450. These
      studies were carried out to investigate whether an appropriate animal model could
      be developed for the human cytochrome(s) P-450 metabolizing tolbutamide.
      Selective induction was used in rats and rabbits to indicate the isozymes
      primarily responsible for tolbutamide hydroxylation in these species. Microsomal
      tolbutamide hydroxylase activity was significantly induced only by phenobarbital
      pretreatment in the rat which induces P-450 forms b (P-450IIB1) and/or e (P
      450IIB2). Only pretreatment of rabbits with rifampicin, which induces cytochrome
      P-450 form 3c (P-450IIIA6), significantly increased the microsomal hydroxylation
      of tolbutamide. However, the increase in tolbutamide hydroxylase activity in
      rifampicin-induced microsomes (congruent to 50%) appears low compared to known
      levels of induction of P-450IIIA6 following rifampicin pretreatment (5-10-fold).
      These data suggest that P-450IIIA6 is at least partially involved in tolbutamide
      hydroxylation in rabbit liver but that other form(s) may be relatively more
      important. Reconstitution experiments with six purified forms of rabbit
      cytochrome P-450 indicated that the highest activity occurred with P-450IIIA6
      (form 3c). As isozymes from different gene families or subfamilies appeared to
      metabolize tolbutamide in the three species studied, catalytic similarities
      between the P-450s with respect to inhibition was further investigated in
      microsomes using sulfaphenazole, alpha-naphthoflavone and mephenytoin. These
      studies showed that the catalytic characteristics in relation to inhibition
      differ markedly between species. Hence, it appears that the animal model approach
      is not likely to be successful in the identification and characterization of the
      cytochrome P-450 form(s) metabolizing tolbutamide in humans.

PMID- 1974200
TI  - Mexiletine metabolism in vitro by human liver.
AB  - Human livers were used in investigations of mexiletine biotransformation in
      vitro. The major metabolic pathways of mexiletine oxidation, to form
      hydroxymethylmexiletine (HMM) and p-hydroxymexiletine (PHM), were characterized
      in liver cell preparations. The localization of reactions in the microsomal
      fraction, their heat lability, NADPH requirement and inhibition by prototype
      cytochrome P-450 (P-450) inhibitors (CO, SKF 525-A, metyrapone and quinidine)
      implied that they were catalyzed by P-450. Kinetic studies of reactions were
      performed in microsomes from five different livers. Eadie-Hofstee plots of data
      gave no indication of systematic deviation from linearity, suggesting that over
      the range of mexiletine concentrations examined (3.3-133.3 microM), HMM and PHM
      were formed by a single enzymatic site. Within a liver preparation, Km and Vmax
      values for HMM and PHM formation were similar. Between livers, Km values of
      reactions were similar with only a 1.8-fold range for each reaction, whereas Vmax
      values showed 7.2- and 7.8-fold ranges for HMM and PHM production, respectively.
      There was a very strong correlation between Vmax values for both reactions. These
      results, coupled with a parallel effect of inhibitors (SKF-525A, metyrapone,
      alpha-naphtoflavone and quinidine) on HMM and PHM formation, argue that both
      reactions are mediated by a common P-450 or closely related isozymes. In
      addition, the present in vitro results support the hypothesis that the
      genetically variable P-450 db 1 isozyme catalyzes the oxidation of mexiletine.

PMID- 1974201
TI  - Glucuronidation of 3'-azido-3'-deoxythymidine by rat and human liver microsomes.
AB  - The glucuronidation of 3'-azido-3'-deoxythymidine (AZT) by rat and human liver
      microsomes has been studied in vitro. The AZT-glucuronide was preliminarily
      identified through specific hydrolysis by beta-glucuronidase and rigorous product
      identification was performed by high-field proton nuclear magnetic resonance and
      fast-atom-bombardment mass spectrometry. A beta-linked 5'-O-glucuronide was the
      exclusive product formed in liver microsomes. Rat and human liver microsomal
      uridine 5'-diphosphoglucuronyltransferase activities toward AZT were
      investigated. These studies revealed that AZT had a lower Km and a 5-6-fold
      higher relative catalytic efficiency for uridine 5'
      diphosphoglucuronyltransferase in human as compared to rat liver microsomes which
      may play a role in the quantitative differences observed in the degree of AZT
      glucuronidation between rat and human.

PMID- 1974202
TI  - Metabolism of alachlor by rat and mouse liver and nasal turbinate tissues.
AB  - The metabolism of alachlor was studied using in vitro incubations with microsomal
      fractions prepared from liver and nasal turbinates of rats and mice.
      Specifically, the transformation of alachlor to 3,5-diethylbenzoquinone-4-imine
      was examined. A key intermediate in this pathway was identified as 2,6
      diethylaniline, the formation of which required catalysis by microsomal
      arylamidases. 2,6-Diethylaniline was oxidized to 4-amino-3,5-diethylphenol and
      the electrophilic 3,5-diethylbenzoquinone 4-imine. Rat nasal tissue possessed
      high enzymatic activity which can promote the formation of the reactive quinone
      imine. Whole body autoradiographic analysis demonstrated localization of
      radioactivity in the rat nasal tissue following oral administration of alachlor.
      A methylsulfide metabolite of alachlor was shown to be a precursor to 2,6
      diethylaniline. The deposition of radioactivity in the rat nasal tissue was more
      pronounced following oral administration of the methylsulfide metabolite of
      alachlor.

PMID- 1974203
TI  - cDNA-directed expression of rat P450s IIA1 and IIA2. Catalytic activities toward
      steroids and xenobiotics and comparison with the enzymes purified from liver.
AB  - Cytochromes P-450IIA1 and IIA2 are steroid hydroxylases that are expressed in rat
      liver. The cDNAs for these enzymes were recently sequenced and compared. To study
      and compare the catalytic activities of IIA1 and IIA2, their cDNAs were inserted
      into a vaccinia virus expression vector and expressed in human hepatoma Hep G2
      cells. IIA2 was able to efficiently catalyze ethoxycoumarin O-deethylation and
      propoxycoumarin O-depropylation, while IIA1 was inactive toward these substrates.
      Neither enzyme could catalyze ethoxy- and pentoxyresorufin dealkylation
      reactions. Both cDNA-expressed IIA1 and IIA2 metabolize testosterone and these
      activities were quantitatively and qualitatively similar to those obtained with
      the purified enzymes. IIA1 produced 7 alpha-hydroxy, 6 alpha-hydroxy, and delta 6
      testosterone at ratios of 9:0.5:0.5 while IIA2 formed 15 alpha
      hydroxytestosterone, an unknown metabolite and four minor metabolites.
      Progesterone metabolism was also studied. IIA1 yielded a 9.5:0.5 ratio of 7 alpha
      hydroxy and 6 alpha-hydroxyprogesterone, while IIA2 produced at least six
      metabolites. These studies establish the conditions and verify the reliability
      and accuracy of the vaccinia virus expression system for studies on the
      enzymology of IIA1 and IIA2.

PMID- 1974204
TI  - The effect of primary metabolites of the xanthine-related nootropic drug
      ethimizol on its hepatic extraction ratio.

PMID- 1974205
TI  - Drug utilization in breast-feeding women. A survey in Oslo.
AB  - In a retrospective questionnaire survey of 885 women who had given birth 3-5
      months before, fewer of those who were still breast-feeding at 4 months (n = 645)
      were using drugs than those who had stopped breast-feeding before 4 months (n =
      240), during the 2 week period preceding registration. The average number of
      doses (Defined Daily Doses/1000 women/day) was 166 and 307, respectively, in that
      period. The number of doses taken was significantly associated with the use of
      oral contraceptive agents (p less than 0.005) and young maternal age (p less than
      0.05). Most of the variation in drug use between breast-feeding and not breast
      feeding mothers was probably due to the greater use of contraception by the
      latter. The number of drugs used per mother in the 4 month period seemed to be
      best predicted by her and her infant's disorders. Long-term medication in breast
      feeding women included many drugs for which there is incomplete or no data about
      milk transfer, e.g. salbutamol, clemastine, dexchlorpheniramine,
      phenylpropanolamine, cromoglycate and levomepromazine. The disorders most
      extensively treated with drugs in this period were dyspepsia, haemorrhoids and
      inflammation of the breast. The finding that smoking was associated with early
      weaning and consumption of alcohol with prolonged breast-feeding calls for
      further investigation. More information on these drug and health issues to the
      breast-feeding mother is highly desirable.

PMID- 1974206
TI  - Investigation of possible pharmacokinetic and pharmacodynamic interactions
      between epanolol and digoxin.
AB  - The possibility of a pharmacokinetic and/or pharmacodynamic interaction between
      epanolol and digoxin has been investigated in 10 healthy male subjects taking
      digoxin 0.375 mg daily for 14 days. During that period epanolol 200 mg daily or
      matching placebo was also given, each for 7 days, according to a double-blind,
      randomized cross-over plan. The plasma digoxin concentration-time profiles after
      7 days of concomitant placebo or epanolol were comparable. Trough and peak plasma
      digoxin levels were similar (placebo: 0.84 and 2.62 ng.ml-1; epanolol: 0.87 and
      2.46 ng.ml-1). The renal clearances of digoxin and creatinine were lower during
      treatment with epanolol, but the differences were not significant (placebo 142.0
      and 126.5 ml.min-1; epanolol 105.7 and 109.3 ml.min-1). STI indexes were lower
      during treatment with digoxin plus epanolol, than after digoxin alone. The
      difference was significant for QS2I (513 versus 503 ms), PEPI (119 versus 112 ms)
      and PEP/LVET (0.286 versus 0.304). The observations suggest that in healthy
      volunteers there is no pharmacokinetic interaction between epanolol and digoxin,
      and that epanolol does not interfere with the positive inotropic action of
      digoxin.

PMID- 1974208
TI  - Chromosomal abnormality limited to T4 lymphocytes in a patient with T-cell
      chronic lymphocytic leukaemia.
AB  - Cytogenetic, immunologic and DNA studies were performed on a patient with the T
      cell type of chronic lymphocytic leukaemia. Standard G-banding karyotype analysis
      revealed clonal chromosome abnormalities with the karyotype 42-44,XY,-11,-12,-13,
      16,-21,-22,i(8q),inv(14) (q11q32), t(15;?)(p11;?), +4-6mar/43
      44,X,t(Y;14)(p11;q11),-11,-12, -13,-21,
      22,i(6p),i(8q),inv(14)(q11q32),t(15;?)(q11;?), +1-3mar. MAC (morphology,
      antibody, chromosomes) methodology, which allows the immunophenotyping of mitotic
      cells, showed that the chromosome abnormalities were restricted to CD4-positive
      helper/inducer T lymphocytes and that CD8 suppressor/cytotoxic T cells and B
      lymphocytes possessed a normal karyotype. The results also indicate that the
      proportion of abnormal metaphases and the overall mitotic activity after 3.5 days
      of stimulation in vitro were highest when PHA and TPA were used as mitogens. When
      the culture period in the presence of PHA + IL-2 was extended, the proportion of
      the abnormal cell population decreased in direct relation to the length of the
      culture period, ranging from 100% at 3.5 d to 0% at 31 d after stimulation.
      Southern blotting analysis revealed rearrangements of both the immunoglobulin
      heavy chain gene and the beta T-cell receptor gene.

PMID- 1974207
TI  - Soluble and surface-bound immunoglobulin triggers human monocyte activation and
      hydrogen peroxide release.
AB  - Human mononuclear phagocytes (MO) can mediate the destruction of a variety of
      foreign and tumor target cells. In most circumstances, however, peripheral blood
      MO are noncytotoxic and must acquire cytotoxic activity. To investigate the cell
      surface molecules that participate in the acquisition of MO-mediated
      cytotoxicity, we used a panel of monoclonal antibodies (MAbs) recognizing a
      variety of membrane molecules. MAbs to eight different MO surface molecules did
      not trigger the killing of tumor target cells. To determine if these cell surface
      molecules triggered an activated but incomplete lytic mechanism, the ability of
      these molecules to trigger hydrogen peroxide (H2O2) release was assessed. Several
      MAbs triggered H2O2 release from MO isolated from the peripheral blood. The
      pattern of MAb-triggered H2O2 release correlated not with the MO surface antigen,
      but with the immunoglobulin (Ig) isotype. Isotype-specific H2O2 release was
      abrogated with the enzymatic removal of the Fc portion of the Ig and enhanced by
      interferon-gamma pretreatment, indicating that the membrane signal was mediated
      by cell surface Fc receptors. H2O2 release was independent of the presentation of
      the Ig molecule. Comparable H2O2 release was observed whether the Ig was in
      surface-bound or soluble form. These data support an important role for Fc
      receptors in the acquisition of cytotoxic potential by human MO.

PMID- 1974209
TI  - The principal difference in regulation of the catalytic activity of water-soluble
      and membrane forms of enzymes in reversed micelles. Gamma-glutamyltransferase and
      aminopeptidase.
AB  - The regularities of their functioning of enzyme, water-soluble and membrane
      forms, in the systems of the reversed micelles of surfactants in organic solvents
      are compared. Using as examples gamma-glutamyltransferase (in AOT reversed
      micelles in octane) and aminopeptidase (in Brij 96 reversed micelles in
      cyclohexane), the principal difference in the catalytic activity regulation of
      water-soluble and membrane forms is demonstrated. The catalytic activity of the
      membrane form depends considerably on the surfactant concentration at the
      constant degree of hydration, whereas the activity of the water-soluble form is
      constant under these conditions. The catalytic activity dependence on the
      surfactant concentration is regarded as a test for enzyme membrane activity.

PMID- 1974210
TI  - New operative strategy in the treatment of metastasizing medullary carcinoma of
      the thyroid.
AB  - Medullary carcinoma of the thyroid (MTC) is exceptional in that the hormone
      calcitonin produced by the tumor cells represents a specific and sensitive tumor
      marker. Careful screening by serial calcitonin determinations following
      pentagastrin stimulation allows for the early detection of metastatic disease. We
      have adopted a method of meticulous modified radical neck dissection to eradicate
      persistent or recurrent MCT in 11 patients treated over a 15-month period. This
      surgical approach resulted in potentially curative treatment in two patients.
      Effective tumor reduction was achieved in another seven. Two patients have
      persistent or progressive disease despite maximum efforts to eradicate malignant
      tissue. Follow-up is presently incomplete in one patient. Postoperative
      complications included recurrent nerve paralysis (n = 3), hypoparathyroidism (n =
      2), muscular weakness (n = 2) and Horner's syndrome (n = 3). The majority of
      nervous complications improved spontaneously. It is concluded that the adopted
      method of meticulous modified radical neck dissection offers the chance of cure
      to some patients and results in the removal of substantial tumor mass in the
      majority of others. Postoperative problems are mostly temporary and are deemed
      acceptable.

PMID- 1974211
TI  - [Work organization in pediatric gynecology].

PMID- 1974212
TI  - Immune mechanisms in choroido-retinal inflammation in man.
AB  - The immunohistopathological findings of enucleated eyes and immunological
      abnormalities in several clinical disorders which result in intraocular
      inflammation are presented. With current immunological techniques, it is possible
      to define the type and activation status of the cells infiltrating the tissues.
      In all eyes examined, the predominant cell type was of activated CD4+ T-cells
      suggesting that the mechanisms involved in the perpetuation of the inflammatory
      response are similar and it is the initiating events which are likely to
      determine the site of pathology. The effects of activated CD4+ T-cells and the
      lymphokines they secrete in the chronic inflammatory process in the ocular
      tissues are discussed.

PMID- 1974213
TI  - Plasma glutamate levels in normal subjects and in patients with amyotrophic
      lateral sclerosis.

PMID- 1974214
TI  - Effect of histamine receptor blockers on human platelet aggregation.

PMID- 1974215
TI  - Involvement of glutamate as a carbon source in nitrogen-fixing Rhizobium
      meliloti.

PMID- 1974216
TI  - HLA-DQ beta-chain restriction fragment length polymorphism as a risk marker in
      type 1 (insulin-dependent) diabetes mellitus: a Finnish family study.
AB  - Finnish Type 1 (insulin-dependent) diabetic families were analysed for HLA-DQ
      beta-chain polymorphism using a short intron-specific probe. A simple
      hybridization pattern was obtained in which all fragments were associated
      significantly with Type 1 diabetes. The simultaneous presence of two different
      risk markers, the allelic 12-kilobase and 4-kilobase fragments were strongly
      associated with Type 1 diabetes since 50% of the patients had this combination
      compared with only 2% of the control subjects. The cosegregated 7.5/3.0 kilobase
      fragments, which were associated with HLA-DR2 and DRw6 were not detected among
      the diabetic patients but were present in 48% of the control subjects. Our
      results provide further support for the location of susceptibility determining
      factors in the HLA-DQ gene area. The clear-cut, simple restriction fragment
      length polymorphism pattern obtained here, which bears a resemblance to a two
      allelic system, therefore makes this method applicable for estimating the risk of
      Type 1 diabetes at the population level.

PMID- 1974217
TI  - Somatostatin monoclonal antibody immunoneutralization increases gastrin and
      gastric acid secretion in urethane-anesthetized rats.
AB  - The role of endogenous somatostatin in mediating urethane anesthesia-induced
      inhibition of gastric acid secretion was investigated using measurement of
      somatostatin messenger RNA concentrations in the antrum and the influence of
      somatostatin monoclonal antibody CURE.S6 on acid secretion in rats anesthetized
      with urethane and acutely implanted with gastric fistulas. Fifteen minutes after
      injection of urethane, somatostatin messenger RNA concentrations were increased
      by 128% compared with those in nontreated rats. The significant elevation of
      somatostatin messenger RNA was maintained for 2 hours after injection.
      Somatostatin monoclonal antibody injected intravenously (2 mg) completely
      reversed the inhibitory effect of somatostatin (20 micrograms/kg.h) on
      pentagastrin (24 micrograms/kg.h)-stimulated gastric acid secretion. The
      somatostatin monoclonal antibody dose dependently increased basal gastric acid
      secretion in urethane-anesthetized rats. Peak acid response to the somatostatin
      monoclonal antibody (2 mg) was observed 20 minutes after antibody injection
      (preinjection, 1.4 +/- 1.2 mumol/10 min; postinjection, 10.6 +/- 0.6 mumol/10
      min); meanwhile, levels of plasma gastrin increased from 27 +/- 6 pg/mL to 75 +/-
      8 pg/mL and were maintained elevated for the 2-hour experimental period. When
      gastrin monoclonal antibody 28.2 was injected together with somatostatin
      monoclonal antibody, the stimulatory effect of the somatostatin antibody was
      inhibited by 82%. A control monoclonal antibody 109-21 directed against the
      biologically inactive glycine-extended fragment 66-72 of progastrin did not alter
      basal gastric acid secretion or the inhibitory effect of somatostatin. These
      results indicate that one mechanism by which urethane induced low basal gastric
      acid secretion involved increased synthesis and release of endogenous
      somatostatin and associated inhibition of gastrin secretion.

PMID- 1974218
TI  - Release of somatostatin immunoreactivity from human antral D cells in culture.
AB  - A primary culture of human antral somatostatin cells has been developed and used
      in release studies. The phorbol ester, phorbol 12 myristate 13-acetate, caused a
      concentration-dependent increase in immunoreactive somatostatin secretion with a
      1-mumol/L concentration resulting in a 40-fold stimulation (basal 0.28% +/- 0.7%
      total cell content vs. 13.8% +/- 2.2% TCC, P less than 0.005). The calcium
      ionophore, A23187, resulted in a significant stimulation only at 1 mumol/L (basal
      0.28% +/- 0.7% TCC vs. 2.2% +/- 0.5% total cell content, P less than 0.05).
      However, addition of the ionophore at 1 mumol/L with the phorbol ester resulted
      in a potentiation of the response at all concentrations tested. Removal of
      extracellular calcium by chelation with EGTA reduced the response to that seen
      with the phorbol ester alone. Forskolin at 0.1 mmol/L resulted in a five-fold
      increase (basal 0.6% +/- 0.2% total cell content vs. 2.8% +/- 0.9% total cell
      content, P less than 0.02) and was 1000-fold less potent than the phorbol ester.
      The peptides bombesin and gastrin at concentrations up to 1 mumol/L had no effect
      on basal secretion. Cholecystokinin-8 significantly stimulated somatostatin
      secretion with a maximal effect at 0.1 mumol/L resulting in an eightfold increase
      (basal 0.2% +/- 0.04% total cell content vs. 1.5% +/- 0.4% total cell content, P
      less than 0.02). These results indicate that human antral D cells are more
      responsive to agents acting through the c-kinase pathway (phorbol 12 myristate 13
      acetate, A23187, and cholecystokinin) than adenylate cyclase (forskolin).

PMID- 1974219
TI  - Pathogenesis and treatment of neuroleptic malignant syndrome.
AB  - 1. Neuroleptic drugs (antipsychotics) produce numerous side effects which include
      serious extrapyramidal symptoms consisting of akathisia, dystonia, neuroleptic
      malignant syndrome, parkinsonian reactions such as postural abnormality, tremor,
      akinesia or bradykinesia, rigidity, and tardive dyskinesia. 2. Among the
      complications of neuroleptic chemotherapy, the most serious and potentially fatal
      complication is malignant syndrome, which is characterized by extreme
      hyperthermia, "lead pipe" skeletal muscle rigidity causing dyspnea, dysphagia,
      and rhabdomyolysis, autonomic instability, fluctuating consciousness,
      leukocytosis, and elevated creatine phosphokinase. 3. Neuroleptic malignant
      syndrome should be differentiated from malignant hyperthermia, lethal catatonia,
      and other pathological states producing some of these same symptoms. 4. In
      addition to neuroleptics, malignant syndrome has been caused by thymoleptics
      (antidepressants), metoclopramide (antiemetic), metoclopramide combined with
      cimetidine, tetrabenazine, overdosage of benzodiazepine, phenelzine, dothiepin
      and alcohol, and amphetamine. 5. Factors leading to and/or facilitating the
      emergence of neuroleptic malignant syndromes are reportedly organic brain
      syndrome, dehydration, exhaustion, external heat load, excessive sympathetic
      discharge, use of long acting neuroleptics, high doses of neuroleptics, rapid
      dose titration with neuroleptics, abrupt discontinuation of antiparkinsonism
      agents, and concurrent lithium therapy. 6. Although, the pathogenesis of
      neuroleptic malignant syndrome is not understood completely, a blockade of
      dopaminergic receptors in the hypothalamus, spinal cord and striatum, an
      alteration of dopaminergic-serotonergic transmission in the body, an enhanced
      synthesis and action of prostaglandin E1 and E2, and a modification of calcium
      mediated signal transduction in the body have been suggested. 7. The treatment of
      malignant syndrome includes immediate withdrawal of neuroleptic drugs, i.v.
      infusion of dantrolene, and oral administration of bromocriptine; or
      alternatively i.v. infusion of dantrolene and the combination of levodopa
      carbidopa. 8. Other measures to enhance the therapeutic effectiveness of the
      aforementioned regimens are to include the use of anticholinergic drugs such as
      benztropine to enhance the effectiveness of bromocriptine, of lorazepam if
      catatonic symptoms persist, or of electroconvulsive therapy (ECT) if psychotic
      symptoms persist. 9. These treatments, however, must be "active" rather than
      "passive", in order to avert fatalities and/or unfortunate sequelae from this
      iatrogenic and incompletely understood disease.

PMID- 1974220
TI  - Cardiovascular responses to adrenergic agonists in sinoaortic denervated rats.
AB  - 1. The cardiovascular effects of systemic alpha and beta adrenergic stimulation
      were studied in conscious sham-operated and sinoaortic denervated (SAD) rats, 7
      days after the corresponding operation. 2. SAD does not modify the pressor
      response to phenylephrine (0.125-8 micrograms.kg-1, i.v.). The blood pressure
      increase was compensated for bradycardia in the sham-operated rats but not in the
      SAD. Only 8 micrograms.kg-1 of phenylephrine induced a slight fall of heart rate
      in the denervated animals. 3. The beta adrenergic agonist isoproterenol (7.8
      ng.kg-1-2 micrograms.kg-1, i.v.) showed a greater hypotensive and a lesser
      tachycardic action in SAD than in sham-operated rats. However, these differences
      disappeared after autonomic ganglionic blockade (hexamethonium, 10 mg.kg-1,
      i.v.). 4. Our results suggest that after 7 days of SAD the pressor response to
      alpha adrenergic agonists may be unaltered and that the differences in the
      cardiovascular beta adrenergic response of SAD rats may be due to loss of the
      baroreflex mechanisms of cardiovascular compensation.

PMID- 1974221
TI  - Opioid receptors and prejunctional modulation of capsaicin-sensitive sensory
      nerves in guinea-pig left atrium.
AB  - 1. In the isolated electrically driven left atria from reserpine-pretreated
      guinea-pigs and in presence of 1 microM atropine, electrical field stimulation
      (EFS) at 10 Hz produces a delayed positive inotropic response (DPIR) involving
      activation of capsaicin-sensitive afferents. 2. Opioids inhibited the DPIR with
      the following order of potency: dermorphin greater than [D-Ala2,N-MePhe4, Gly5
      ol]-enkephalin (DAGO) greater than or equal to [D-Ala2,D-Leu5]-enkephalin (DADLE)
      greater than morphine greater than dynorphin A (1-13) greater than [D-Pen2,D
      Pen5]-enkephalin (DPDPE). U-50488 was ineffective up to 10 microM. 3. Opioids
      also inhibited resting inotropism (3 Hz) with the following rank order of
      potency: DADLE greater than DAGO greater than U-50488 = dynorphin A (1-13) =
      morphine = DPDPE. 4. Both inhibition of the DPIR and inhibition of resting
      inotropism were prevented by 10 microM naloxone. 5. Neither dermorphin (0.1
      microM) nor DAGO (0.3 microM) or DADLE (1 microM) inhibit responses produced by
      capsaicin (30 nM) or calcitonin gene-related peptide (3 nM). 6. These findings
      indicate that capsaicin-sensitive nerves in the guinea-pig atrium are endowed
      with mu opioid receptors which inhibit transmitter release when sensory nerve
      terminals are activated by EFS but not by capsaicin.

PMID- 1974222
TI  - The effects of clozapine on rat mast cells are different from those of
      benzodiazepines.
AB  - 1. Clozapine caused dose-dependent inhibition of the release of [14C]serotonin
      and 45Ca uptake by purified rat peritoneal mast cells activated by concanavalin
      A, which is similar to the effect of benzodiazepines. 2. However, it had little
      ability to displace [3H]diazepam binding to mast cells.

PMID- 1974223
TI  - Colonial variation and fimbriation of Actinobacillus actinomycetemcomitans.
AB  - Three colonial variants of Actinobacillus actinomycetemcomitans, which formed
      transparent rough (TR)-, transparent smooth (TS)-, and opaque smooth (OS)
      surfaced colonies, were described in relation to their fimbriation. TR- and TS
      cells were adhesive to agar and glass surfaces but not the OS-cells. The
      examination by electron microscopy revealed that TR-cells were highly fimbriated
      but not TS- and OS-cells. Thus, TS-cells seemed to be an intermediate type. The
      fimbriae were isolated from TR-cells by suspending in 0.15 M ethanolamine-HCl
      buffer (pH 10.5) and purified by dissolving non-fimbrial components in 0.5%
      deoxycholate and 0.7% n-octyl-beta-D-glucopyranoside. The relative molecular mass
      of the fimbrial subunit protein was 54,000.

PMID- 1974225
TI  - Is there selection on RFLP differences in mitochondrial DNA?
AB  - Experimental populations of Drosophila simulans were established for the purpose
      of detecting the presence or absence of selection on a restriction fragment
      length polymorphism in mitochondrial DNA (mtDNA). It was then discovered that the
      founding strains differed with respect to the Rickettsia-mediated incompatibility
      system in this species, which is maternally transmitted together with the mtDNA
      differences. A population model was constructed using the known fitness effects
      of the incompatibility system, with the result that the population trajectories
      can be completely explained by the effects of the microorganism with no need to
      invoke selection on mtDNA. The strong conclusion is that in this case we can rule
      out the strong selection proposed by MacRae and Anderson to explain the "dramatic
      mtDNA changes" in their Drosophila pseudoobscura populations. The population
      theory used for the experiments is discussed in the context of natural
      populations. Estimated parameters include the possibility that with two
      populations, one with the organism and one without it, there may be no bias as to
      which will invade the other, which in turn suggests no global tendency for the
      infection to spread or decline.

PMID- 1974224
TI  - Molecular and phenotypic variation of the Zw locus region in Drosophila
      melanogaster.
AB  - Restriction map polymorphism in a 13-kb region of the Zw locus in Drosophila
      melanogaster was investigated for 64 X chromosome lines with seven 6-cutter and
      ten 4-cutter restriction enzymes. A total of 203 restriction sites were scored,
      of which 20 were found to be polymorphic. The estimated nucleotide variation for
      this region for overall data (pi = 0.003 and 0.001, and theta = 0.003 and 0.002,
      for 4-cutter and 6-cutter studies, respectively) was smaller than that reported
      for most regions studied in D. melanogaster. It was found that the Slow allozyme
      has a larger nucleotide variation and haplotype diversity than the Fast allozyme.
      Results suggest the relatively recent divergence of the Fast allozyme from the
      Slow allozyme. Glucose 6-phosphate dehydrogenase (G6PD) activity was measured as
      a phenotype of the Zw locus. A significant difference in G6PD activity between
      allozymes was detected. The between-line effect was highly significant within the
      Slow allozyme, but was not significant within the Fast allozyme. Although a
      direct causative link could not be established, these results suggest an
      association between the amounts of quantitative and molecular genetic variation
      at the Zw locus region.

PMID- 1974226
TI  - Parental analysis of introgressive hybridization between African and European
      honeybees using nuclear DNA RFLPs.
AB  - African honeybees, introduced into Brazil 33 years ago, have spread through most
      of South and Central America and have largely replaced the extant European bees.
      Due to a paucity of genetic markers, genetic interactions between European and
      African bees are not well understood. Three restriction fragment length
      polymorphisms (RFLPs), detected with random, nuclear DNA probes, are described.
      The polymorphisms are specific to bees of European descent, possibly specific to
      certain European races. Each European marker was found present at a high
      frequency in U.S. colonies but absent in South African bees. Previous
      mitochondrial DNA studies of neotropical bees have revealed negligible maternal
      gene flow from managed European apiaries into feral African populations. The
      findings reported here with nuclear DNA show paternal gene flow between the two
      but suggest asymmetries in levels of introgressive hybridization. Managed
      colonies in southern Mexico, derived from European maternal lines, showed
      diminished levels of the European nuclear markers, reflecting significant
      hybridization with African drones. The European alleles were present only at low
      frequencies in feral swarms from the same area. The swarms were of African
      maternal descent. In Venezuelan colonies, also derived from African maternal
      lines, the European markers were almost totally absent. The results point to
      limited paternal introgression from European colonies into the African honeybee
      populations. These findings dispute other views regarding modes of
      Africanization.

PMID- 1974227
TI  - Estimation of recombination frequencies and construction of RFLP linkage maps in
      plants from crosses between heterozygous parents.
AB  - The construction of a restriction fragment length polymorphism (RFLP) linkage map
      is based on the estimation of recombination frequencies between genetic loci and
      on the determination of the linear order of loci in linkage groups. RFLP loci can
      be identified as segregations of singular or allelic DNA-restriction fragments.
      From crosses between heterozygous individuals several allele (fragment)
      configurations are possible, and this leads to a set of formulas for the
      evaluation of p, the recombination frequency between two loci. Tables and figures
      are presented illustrating a general outline of gene mapping using heterozygous
      populations. The method encompasses as special cases the mapping of loci from
      segregating populations of pure lines. Formulas for deriving the recombination
      frequencies and information functions are given for different fragment
      configurations. Information functions derived for relevant configurations are
      also compared. A procedure for map construction is presented, as it has been
      applied to RFLP mapping in an allogamous crop.

PMID- 1974228
TI  - The homeo domain protein rough is expressed in a subset of cells in the
      developing Drosophila eye where it can specify photoreceptor cell subtype.
AB  - The Drosophila homeo box gene rough is required in photoreceptor cells R2 and R5
      for normal eye development. We show here that rough protein expression is limited
      to a subset of cells in the developing retina where it is transiently expressed
      for 30-60 hr. The rough protein is first expressed broadly in the morphogenetic
      furrow but is rapidly restricted to the R2, R3, R4, and R5 precursor cells.
      Ubiquitous expression of rough under the control of the hsp70 promoter in third
      instar larvae suppresses the initial steps of ommatidial assembly. Structures
      derived from other imaginal discs are not affected. Ectopic expression of rough
      in the R7 precursor, through the use of the sevenless promoter, causes this cell
      to develop into an R1-6 photoreceptor subtype; however, this cell still requires
      sevenless function for its neural differentiation. Taken together with previous
      analyses of the rough mutant phenotype, these results suggest that the normal
      role of rough is to establish the unique cell identity of photoreceptors R2 and
      R5.

PMID- 1974229
TI  - Reprogramming cell fate in the developing Drosophila retina: transformation of R7
      cells by ectopic expression of rough.
AB  - In the developing eye of Drosophila, the homeo box gene rough is required in the
      developing photoreceptor cells R2 and R5 for the correct development of the
      neighboring R3 and R4 cells. We have expressed rough ectopically in a limited
      subset of developing ommatidial cells using the sevenless enhancer. Expression of
      rough in the presumptive R7 cell transforms this cell into an R1-6 type
      photoreceptor. This transformation is cell autonomous in contrast to the apparent
      nonautonomy of the rough mutant phenotype and depends on the presence of the
      sevenless gene. We propose that in wild type, rough functions autonomously in the
      specification of R2/5 photoreceptor cell identity but by itself cannot initiate
      neural development.

PMID- 1974230
TI  - Characterization of the transcription unit encoding the major pneumococcal
      autolysin.
AB  - The pneumococcal lytA gene coding for the major autolysin (amidase) can be
      expressed in Streptococcus pneumoniae and Escherichia coli using unchanged
      promoter and termination signals. A region containing several -10, -35 and -44
      promoter elements, identical to other previously described prokaryotic promoter
      sequences, has been found upstream from the transcription start point. A
      transcription terminator consisting of a hairpin structure (-20.8 kcal/mol)
      typical of Rho-independent prokaryotic terminators was also localized. The lytA
      gene has a rather long (240-bp) leader sequence with a high A + T content (70%)
      that contrasts with the very short (2-bp) untranslated region of the polA gene
      [Lopez et al., J. Biol. Chem. 264 (1989) 4255-4263], the unique pneumococcal
      transcription unit that had been characterized so far. Although two open reading
      frames have been found in the leader region it seems unlikely that these
      sequences can be translated due to the absence of appropriate ribosome-binding
      sites.

PMID- 1974231
TI  - Construction of a broad-host-range pneumococcal promoter-probe plasmid.
AB  - A promoter-probe plasmid, pLSE4, containing the promoterless lytA gene that
      encodes the major pneumococcal autolysin, was developed to isolate and
      characterize nucleotide sequences of Streptococcus pneumoniae involved in
      transcriptional regulation. This vector was derived from the broad-host-range
      plasmid pLS1 and is suitable for the transformation of Gram- and Gram+ bacteria.
      An array of unique restriction sites was placed upstream from the lytA coding
      region. Pneumococcal promoters can be screened from random DNA fragments cloned
      in these sites for the ability to direct the expression of the autolysin in
      transformed autolysin-deficient pneumococcal cells. Transformants showing a Lyt+
      phenotype were selected on agar plates using a simple filter technique. Relative
      promoter strength was determined by direct assay of the cell wall lytic activity
      in cell extracts.

PMID- 1974232
TI  - A hazardous side effect of neuroleptics: diagnosis and treatment.
AB  - Neuroleptic malignant syndrome (NMS) is a potentially fatal disease process
      characterized by hyperthermia, altered mental status, muscular rigidity, and
      autonomic instability. This syndrome is most often seen in patients who are
      taking neuroleptics and other psychoactive medications. Primary care physicians
      are often the first providers to see patients with this syndrome and must be
      alert to its potential diagnosis. Treatment should be immediate and consists of
      discontinuing the neuroleptic medication; supporting pulmonary, cardiovascular,
      and renal functions, and using bromocriptine and/or dantrolene.

PMID- 1974233
TI  - Electron paramagnetic resonance and spin trapping study of radicals formed during
      reaction of aromatic amines with isoamyl nitrite under aprotic conditions.
AB  - Diazotization of primary aromatic amines with isoamyl nitrite in benzene at room
      temperature was studied employing EPR and spin trapping techniques. Nitrosodurene
      (ND), 2-methyl-2-nitrosopropane (MNP), and 5,5-dimethyl-pyrroline N-oxide (DMPO)
      were used as spin trapping agents. Aryl radicals were detected employing ND and
      MNP. Using DMPO as a spin trap most of the amines produced EPR spectra ascribed
      to adducts with aniline-type radicals (N-centred radicals). The assignments were
      verified using 15N-labeled anilines. Similar spectra of DMPO adducts were
      recorded from amines treated with benzoyl peroxide or benzophenone plus UV.
      Possible mechanisms of formation of these adducts (radical trapping versus
      nucleophilic addition to DMPO followed by oxidation) during treatment of the
      amines with isoamyl nitrite are discussed.

PMID- 1974235
TI  - Scavenger effect of sulphasalazine (SASP), 5-aminosalicylic acid (5-ASA), and
      olsalazine (OAZ)

PMID- 1974236
TI  - [Physiological and neuropharmacological aspects of the central respiratory
      mechanisms].
AB  - The present physiological and neuropharmacological views and the essentials of
      the experimental results on the anatomical localization, functional and neuronal
      organization of the central respiratory mechanisms, classically expressed as the
      respiratory centers, in the brain stem were reviewed and discussed. The brain
      stem neural mechanism for central regulation of breathing is regarded as a
      complex neuronal mechanism consisting of several functional subsystems subserving
      different functions. One of its functions is the generation of respiratory
      rhythm. The subsystem for respiratory rhythm-generating mechanisms is located in
      the medullary reticular formation outside the DRG and VRG regions, which are
      thought to be premotor neuron pools. Rhythmic activity originating in the medulla
      is dominant in terms of the spontaneity over other rhythmic activity in the
      pontine and spinal cord mechanisms. Evidences for heterogeneity of the functional
      properties of brain stem respiratory neurons have been demonstrated. Neuronal
      mechanisms involving respiratory neurons identified as members of the primary
      respiratory neuron population or neuronal networks consisting of different types
      of respiratory neurons located in the lateral region of the bulbar reticular
      formation may play important roles in the generation of respiratory rhythms.
      These aspects contribute to the understanding of the neurophysiological basis,
      providing important prerequisites for further neuropharmacological studies on
      neurotransmission within the neuronal network of the central respiratory
      mechanisms.

PMID- 1974234
TI  - HLA-DP and coeliac disease: family and population studies.
AB  - We investigated polymorphism of HLA-DP genes in three DR3 related diseases,
      confirming an association of coeliac disease with a Bgl II DP alpha polymorphism
      (a restriction fragment sized 3.5 kb present in 75% of patients compared to 34%
      of control subjects, p less than 0.001), and finding a weaker association with
      dermatitis herpetiformis (57% v 34%, p = 0.01) and no association with insulin
      dependent diabetes mellitus. The association with coeliac disease was further
      investigated. Msp I DP beta polymorphism was studied in 52 healthy subjects and
      59 patients: a 4.9 kb fragment was present in 51% of patients with coeliac
      disease compared to 11.5% of control subjects (p less than 0.001). Furthermore,
      nearly all subjects with the DP alpha 3.5 kb fragment also had the DP beta 4.9 kb
      fragment. However, disease frequency was still increased in the DP alpha 3.5
      positive/DP beta 4.9 negative group. In seven families, each with at least two
      affected members, while the DP alpha 3.5 fragment was frequently present in
      patients it did not preferentially segregate with any particular HLA haplotype-
      for example, those associated with DR3 or DR7--and therefore is not part of an
      extended haplotype associated with coeliac disease. We therefore conclude that a
      gene(s) in the HLA-DP region predisposes to coeliac disease independently of the
      HLA-DR/DQ regions.

PMID- 1974237
TI  - [Effects of betaxolol, a cardioselective beta-adrenoceptor antagonist, on
      ischemic myocardial energy and carbohydrate metabolism in dogs].
AB  - The effect of betaxolol, a beta 1-adrenoceptor antagonist, on ischemic myocardial
      metabolism was studied in dog hearts subjected to an occlusion of the left
      anterior descending coronary artery for 10 or 30 min. Betaxolol (0.1 or 0.3
      mg/kg) was injected i.v. 5 min before ischemia. Betaxolol decreased heart rate,
      (+)dp/dt, coronary flow and blood pressure. Coronary occlusion decreased the
      levels of creatine phosphate, adenosine triphosphate, total adenine nucleotides
      and energy charge potential in the ischemic myocardium. Ten minutes after
      ischemia, betaxolol significantly diminished these impairments of energy
      metabolism. Even 30 min after ischemia, a higher dose of betaxolol significantly
      inhibited the depletion of total adenine nucleotides. Myocardial ischemia
      produced a breakdown of glycogen, an accumulation of lactate and an inhibition of
      glycolytic flux through the phosphofructokinase reaction. Betaxolol also reduced
      these alterations of carbohydrate metabolism 10 min after ischemia. These results
      indicate that betaxolol delays the onset of myocardial metabolic change from
      aerobic to anaerobic during ischemia and hence reduces the severity of myocardial
      ischemic injury.

PMID- 1974238
TI  - [Antihypertensive effect of betaxolol, a cardioselective beta-adrenoceptor
      antagonist, in experimental hypertensive rats].
AB  - Betaxolol is a highly selective beta 1-adrenoceptor antagonist without intrinsic
      sympathomimetic activity. In this study, the antihypertensive effect of betaxolol
      was investigated in experimental hypertensive rats; and the antihypertensive
      mechanism was also studied. Betaxolol (1 and 10 mg/kg, p.o.) produced acute
      hypotensive effects in conscious spontaneously hypertensive rats (SHR), renal
      hypertensive rats, deoxycorticosterone/saline hypertensive rats and normotensive
      rats. The effect was particularly marked in SHR. Furthermore, daily oral
      administration of betaxolol to SHR for 3 weeks showed sustained antihypertensive
      effects without producing tolerance. In pithed rats, the pressor response induced
      by an electrical stimulation of the spinal cord was inhibited by both betaxolol
      and atenolol. However, only betaxolol reduced the pressor response to
      norepinephrine. These findings suggest that a certain relaxing effect on
      peripheral vascular beds in addition to inhibition of presynaptic beta
      adrenoceptors may contribute to the antihypertensive mechanism of betaxolol.

PMID- 1974240
TI  - [Effects of alpha- and beta-adrenergic blockers on the lower limits of cerebral
      blood flow autoregulation in spontaneously hypertensive rats].
AB  - The effects of alpha- and beta-adrenergic blockers (phenoxybenzamine, PBZ and
      propranolol, PPL, respectively) on the cerebral (CBF) and cerebellar (CeBF) blood
      flow autoregulations were examined in spontaneously hypertensive rats. CBF and
      CeBF were measured during stepwise hemorrhagic hypotension using hydrogen
      clearance method. The lower limits of autoregulation for CBF beyond which blood
      flow was decreased steeply were 72% of the resting blood pressure level in the
      control, 56% in the PBZ treated group, and 80% in the PPL group. Similar tendency
      was observed in CeBF. These results indicate that PBZ leads to a downward shift
      while PPL to a slight upward shift of the lower limits of CBF and CeBF
      autoregulations, suggesting that alpha-adrenergic blockade has a favorable effect
      for the maintenance of cerebral blood flow during acute reduction of blood
      pressure.

PMID- 1974239
TI  - [Antihypertensive effect of betaxolol, a cardioselective beta-adrenoceptor
      antagonist, in renal hypertensive dogs].
AB  - The antihypertensive effect of betaxolol, a highly selective beta 1-adrenoceptor
      antagonist, was investigated in renal hypertensive dogs, and the mechanism was
      also studied. A single oral administration of betaxolol (1 and 10 mg/kg) lowered
      blood pressure dose-dependently. The hypotensive effect of betaxolol was enhanced
      by daily oral administration for 10 days. In anesthetized dogs, intraarterial
      injection of betaxolol produced a dose-dependent increase in femoral artery flow;
      and in this test, betaxolol was 3 times less potent than papaverine. The increase
      in blood flow with betaxolol was not affected by pretreatment with propranolol.
      These findings indicate that a certain vasodilating activity may contribute to
      the antihypertensive mechanism of betaxolol.

PMID- 1974241
TI  - [Diversity of the HLA-DQ gene].
AB  - Genomic DNA obtained from B lymphoblastoid cell line was digested with
      appropriate restriction endonuclease and hybridized with several probes specific
      for HLA-DQ gene. DNA probe which detects intron between DQ beta 1 and beta 2
      domains suggested the intron insertion event of Alu-like repetitive sequence in
      DR7DQw2 haplotype. Southern hybridization with DQA1 3' untranslated (UT) region
      probe showed DQw2-type hybridization pattern in DR7LDQw3 haplotype. On the
      contrary, DQB1 3'UT region probe showed DQw3-type pattern in the same haplotype,
      which strongly supports the previous suggestion that recombination occurs between
      DQA1 and DQB1 genes in DR7DQw3 haplotype. 3'UT region probes of DQA1 and DQB1
      genes failed to detect restriction fragment lenght polymorphism (RFLP) between
      DR4DQw3 and DR4DQw4 haplotypes. DNA sequencing of DQB1 genomic clone derived from
      KT3 cell line (DR4DQw4) revealed striking homology of beta 2 domain, 5'UT region,
      3'UT region and intervening sequence between beta 1 and beta 2 domains in DR4DQw3
      and DR4DQw4 haplotypes. This structural similarity suggests that DQw3 and DQw4
      genes are generated from a common ancestral gene.

PMID- 1974242
TI  - Restriction fragment length polymorphism (RFLP) at the DNF15S2 locus in three
      ethnic groups of Singapore.
AB  - Three different ethnic groups from Singapore comprising 79 Chinese, 34 Malays and
      23 Indians of Dravidian origin, were investigated for the HindIII RFLP at the
      DNF15S2 locus. The three populations had very similar allele frequencies and the
      frequency of rarer(S) allele was significantly (p less than 0.01) lower (0.21) in
      these ethnic groups compared to that in Caucasians (0.41). The phenotypic
      distributions were at Hardy-Weinberg equilibrium.

PMID- 1974243
TI  - L-arginine-dependent nitric oxide formation and nitrite release in bone marrow
      derived macrophages stimulated with bacterial lipopeptide and lipopolysaccharide.
AB  - This study shows that stimulating bone marrow-derived macrophages with either
      lipopolysaccharide (LPS) or the lipopeptide N-palmitoyl-S-(2,3-bis(palmitoyloxy)
      (2RS)-propyl)-(R)- cysteinyl-alanyl-glycine (Pam3Cys-Ala-Gly), a synthetic
      analogue of the N-terminal part of bacterial lipoprotein, leads to the formation
      of nitric oxide (NO) and nitrite (NO2-), a stable analogue of NO. NO was detected
      by applying the chemiluminescence method and by measuring the activity of
      exogenously added soluble guanylate cyclase (GC), which is strongly and
      selectively activated by NO. Synthesis of NO and NO2- occurs via activation of
      the L-arginine and NADPH-dependent enzyme(s) present in the cytosol of bone
      marrow-derived macrophages. No produced by this non-constitutive L-arginine
      pathway is thought to be responsible for the cytostatic and killing properties of
      macrophages (Stuehr & Nathan, 1989). Macrophages stimulated either with LPS or
      Pam3Cys-Ala-Gly exhibited a 6-hr lag time before engaging in nitrite synthesis, a
      time at which expression of the NO-forming enzyme had already reached its
      maximum. The regulation of NO and NO2- synthesis during macrophage development
      seems to differ from that of cytokine synthesis. Whereas cytokine release varies
      during a culture period up to 20 days, NO synthesis and expression of the NO
      forming enzyme remain unaltered. These studies show that, similar to LPS, Pam3Cys
      Ala-Gly is a potent activator of 'the oxidative L-arginine pathway' in bone
      marrow-derived macrophages. Whether both stimuli use the same signal transfer
      mechanism to induce this pathway and whether NO synthesized by this pathway is
      involved in the activation of the enzyme guanylate cyclase in macrophages
      requires clarification.

PMID- 1974244
TI  - Identification of beta 2-adrenoceptors on guinea pig alveolar macrophages using (
      )-3-[125I]iodocyanopindolol.
AB  - The beta-adrenoceptor antagonist (-)-3-[125I]iodocyanopindolol ([125I]ICYP) binds
      with high affinity and in saturable way to membranes of guinea pig alveolar
      macrophages. The equilibrium dissociation constant for [125I]ICYP is 24.3 +/- 1.2
      pM, and the number of binding sites is 166.3 +/- 13.7 fmol/mg protein (N = 4, +/-
      SEM). Displacement studies with selective antagonists showed that [125I]ICYP
      labels beta 2-adrenoceptors on guinea pig alveolar macrophages.

PMID- 1974245
TI  - Beta-adrenergic therapy for glaucoma.

PMID- 1974246
TI  - Management of an unusually high postpubertal presentation of cryptorchidism.
AB  - A high proportion (43%) of postpubertal presentation of cryptorchid testes was
      found in 114 patients with undescended testes (UDT). Bilateral presentation of
      UDT was observed in 25% of patients. Orchiopexy was performed on 75% of
      postpubertal cases, the determinant factor for choice of operation being cosmetic
      and psychological. Follow-up results appear to be promising in this environment
      with very low incidence of testicular cancer.

PMID- 1974247
TI  - In vitro and in vivo release of soluble erbB-2 protein from human carcinoma
      cells.
AB  - An enzyme-linked immunosorbent assay (ELISA) was developed to measure soluble
      erbB-2 protein in culture supernatants of various human cell lines and sera of
      patients suffering from recurrent breast carcinoma. Soluble erbB-2 protein was
      demonstrated in culture supernatants of cell lines that expressed high levels of
      erbB-2 protein as shown by western blot analysis of cell lysates. Increased
      levels of the protein, 40- to 190-fold higher than in healthy controls, were
      demonstrated in sera of 3 out of 12 patients with breast carcinomas. On
      immunohistological study of tumor tissues from 9 patients, high immune reaction
      with the anti-erbB-2 protein antibody was observed in 2 cases. These were two of
      the three patients who had elevated levels of erbB-2 protein in serum (a sample
      was not available from the third patient). These results raise the possibility
      that soluble erbB-2 protein level in serum can be used as an indicator for spread
      of carcinomas that overexpress erbB-2 protein.

PMID- 1974248
TI  - Potassium induced release of GABA and other substances from the guinea pig
      cochlea.
AB  - Gamma-aminobutyric acid (GABA) has been proposed as a neurotransmitter of a
      subset of efferent nerve fibers in the mammalian cochlea. We tested this
      hypothesis by examining if GABA was released by high concentrations of K+ from
      the guinea pig cochlea. Artificial perilymph solutions containing either normal
      K+ (5 mM) or high K+ (50 mM) were perfused through the perilymphatic compartment
      of the guinea pig cochlea while collecting the effluent. Nineteen primary amines
      including GABA were quantified in the effluent by HPLC. This was carried out in
      normal animals and in animals pretreated with ethacrynic acid and kanamycin to
      destroy the organ of Corti. Significantly greater levels of GABA, taurine,
      glutamate, aspartate, glycine and three unidentified substances appeared in
      effluent collected during exposure of the cochlea to solutions containing higher
      K+ than normal K+. Compared to normal animals, destruction of the organ of Corti
      significantly decreased the K(+)-induced release of GABA, taurine, glutamate,
      aspartate, glycine and one of the unidentified substances; although significant
      release of glutamate and taurine still occurred in the destroyed ears. The
      release of GABA is consistent with it being a neurotransmitter in the cochlea. In
      addition the results: confirm the release of glutamate and taurine from the organ
      of Corti; suggest that additional substances may be released; and demonstrate the
      release of glutamate and taurine from tissue other than the organ of Corti.

PMID- 1974250
TI  - Structure of transglutaminases.

PMID- 1974249
TI  - Neuroleptic withdrawal in patients meeting criteria for supersensitivity
      psychosis.
AB  - In an attempt to prospectively validate the existence of supersensitivity
      psychosis (SSP), five schizophrenic patients meeting Chouinard's criteria for SSP
      and five non-SSP schizophrenic controls had neuroleptic treatment withdrawn for 2
      weeks under double-blind conditions. The sudden worsening of psychotic symptoms
      and tardive dyskinesia postulated in the SSP group was not observed on the Brief
      Psychiatric Rating Scale, the Clinical Global Impressions scale, and the
      Abbreviated Dyskinesia Rating Scale. In conclusion, the authors' pilot data do
      not seem to support the existence of SSP.

PMID- 1974251
TI  - Acetyl-CoA carboxylase mRNA species with or without inhibitory coding sequence
      for Ser-1200 phosphorylation.
AB  - Acetyl-CoA carboxylase (ACC) is the rate-limiting enzyme in the biogenesis of
      long chain fatty acids. The phosphorylation of the Ser-1200 residue by cyclic AMP
      dependent protein kinase transforms ACC from a citrate-independent form to a
      citrate-dependent form (10, 16). We have isolated ACC cDNA clones with and
      without 24 bases which code for 8 additional amino acids located 4 residues
      upstream to the Ser-1200. The presence of the 8 extra amino acids inhibits the in
      vitro phosphorylation of the Ser-1200 by the catalytic subunit of cyclic AMP
      dependent protein kinase. The S1 nuclease protection experiments indicate that
      the corresponding two ACC mRNA species occur in vivo. Furthermore, the occurrence
      of the two forms of ACC mRNA is regulated under different physiological
      conditions for lipogenesis in a tissue-specific manner. The existence of two
      forms of ACC mRNA provides the basis for the existence of isozymes of ACC whose
      Ser-1200 can be selectively phosphorylated. The location of this regulatory
      sequence for a specific phosphorylation site represents a new regulatory
      mechanism for protein phosphorylation.

PMID- 1974252
TI  - Isolation and characterization of an L1210 cell line retaining the sodium
      dependent carrier cif as its sole nucleoside transport activity.
AB  - Nucleoside permeation across mammalian cell membranes is complex with at least
      four distinct transporters known. Two of these (es and ei) are equilibrative
      (facilitated diffusion) carriers that have been studied is considerable detail.
      The other two (cif and cit) are concentrative, Na(+)-dependent carriers. A major
      obstacle to the characterization of the latter two mechanisms has been the lack
      of suitable model systems expressing only a single nucleoside transport activity.
      The present study describes the isolation of a cell line that has cif as its sole
      nucleoside transporter. L1210/MC5-1 cells, which have es and cif transport
      activity, were mutagenized and plated in soft agar containing two cytotoxic
      nucleosides (tubercidin (7-deazaadenosine) and cytosine arabinoside) that are
      substrates for es but not cif. A clonal line (L1210/MA-27.1) was isolated which
      retained the capacity for Na(+)-dependent [3H]formycin B transport but was unable
      to transport [3H]thymidine, a substrate for es but not cif. Failure of the mutant
      to transport thymidine was also demonstrated by the inability of thymidine (with
      adenine as a purine source) to rescue these cells from methotrexate toxicity.
      Furthermore, the mutant lacked nitrobenzylthioinosine (NBMPR) binding activity
      (an integral part of the es transporter) as demonstrated by reversible NBMPR
      binding and photoaffinity labeling with [3H]NBMPR. Loss of es transport activity
      was also demonstrated by the failure of NBMPR to affect the toxicity of 2
      chlorodeoxyadenosine (IC50 approximately 30 nM) in L1210/MA27.1 cells. In
      contrast, NBMPR decreased the IC50 for 2-chlorodeoxyadenosine from 100 to 30 nM
      in the parental L1210/MC5-1 cell line. These results are consistent with the
      mechanism of NBMPR potentiation of 2-chlorodeoxyadenosine toxicity in L1210 cells
      being a blockade of efflux via es while the nucleoside is pumped into the cells
      by the concentrative cif carrier.

PMID- 1974253
TI  - ATP-dependent and NAD-dependent modification of glutamine synthetase from
      Rhodospirillum rubrum in vitro.
AB  - Glutamine synthetase from the photosynthetic bacterium Rhodospirillum rubrum is
      the target of both ATP- and NAD-dependent modification. Incubation of R. rubrum
      cell supernatant with [alpha-32P]NAD results in the labeling of glutamine
      synthetase and two other unidentified proteins. Dinitrogenase reductase ADP
      ribosyltransferase does not appear to be responsible for the modification of
      glutamine synthetase or the unidentified proteins. The [alpha-32P]ATP- and [alpha
      32P] NAD-dependent modifications of R. rubrum glutamine synthetase appear to be
      exclusive and the two forms of modified glutamine synthetase are separable on two
      dimensional gels. Loss of enzymatic activity by glutamine synthetase did not
      correlate with [alpha-32P]NAD labeling. This is in contrast to inactivation by
      nonphysiological ADP-ribosylation of other glutamine synthetases by an
      NAD:arginine ADP-ribosyltransferase from turkey erythrocytes (Moss, J., Watkins,
      P.A., Stanley, S.J., Purnell, M.R., and Kidwell, W.R. (1984) J. Biol. Chem. 259,
      5100-5104). A 32P-labeled protein spot comigrates with the NAD-treated glutamine
      synthetase spot when glutamine synthetase purified from H3 32PO4-grown cells is
      analyzed on two-dimensional gels. The adenylylation site of R. rubrum glutamine
      synthetase has been determined to be Leu-(Asp)-Tyr-Leu-Pro-Pro-Glu-Glu-Leu-Met;
      the tyrosine residue is the site of modification.

PMID- 1974254
TI  - Protein-protein interactions facilitate DNA binding by the glucocorticoid
      receptor DNA-binding domain.
AB  - We have studied the interaction of the DNA-binding domain of the glucocorticoid
      receptor with a glucocorticoid response element from the tyrosine
      aminotransferase gene. This response element consists of two binding sites (half
      sites) for the glucocorticoid receptor DNA-binding domain. The sequences of these
      two half-sites are not identical, and we have previously shown that binding
      occurs preferentially to one of the half-sites (Tsai, S.-Y., Carlstedt-Duke, J.,
      Weigel, N. L., Dahlman, K., Gustafsson, J.-A., Tsai, M.-J., and O'Malley, B. W.
      (1988) Cell 55, 361-369). We show here that binding to the low affinity half-site
      is dependent on previous occupancy of the high affinity half-site. This
      facilitated binding is dependent on the distance between the two half-sites and
      their relative orientation but is not dependent on the integrity of the DNA
      backbone. This is consistent with a model where DNA binding is not only dependent
      on interactions between the protein and its DNA target sequence but is also
      influenced by interactions between the protein molecules bound.

PMID- 1974255
TI  - Effects of prolonged infusion of dopexamine on beta 1- and beta 2-adrenoceptors
      in guinea-pig myocardium.
AB  - 1. The effects of 7-day infusion of dopexamine (50 and 200 micrograms kg-1h-1)
      were examined on beta 1- and beta 2-adrenoceptors in guinea-pig left ventricular
      membranes. 2. Receptor binding performed using the high affinity radioligand (-)
      [125I]-cyanopindolol (CYP) and the beta 1-adrenoceptor antagonist CGP 20712A
      showed that treatment with dopexamine 200 micrograms kg-1h-1 caused a 45%
      reduction in beta 2-adrenoceptors and a small but not significant increase in
      beta 1-adrenoceptors. 3. Functional effects of dopexamine were examined in the
      guinea-pig isolated electrically driven left atria and K(+)-depolarized uterus.
      Dopexamine was an antagonist at beta 1-adrenoceptors in left atria (pKB = 4.49),
      and a partial agonist at beta 2-adrenoceptors in the uterus (alpha = 0.78, pD2 =
      6.59). 4. The effects of dopexamine on beta 1- and beta 2-adrenoceptor density in
      guinea-pig ventricular myocardial membranes may be related to agonist activity at
      beta 2-adrenoceptors and antagonist activity at beta 1-adrenoceptors.

PMID- 1974256
TI  - Ocular inhibitory effects of the dopamine DA2 agonist (Ha-118) in cats and
      rabbits.
AB  - 1. Topical administration of the dopamine (DA2) receptor agonist, Ha-118,
      produced unilateral ocular hypotension and miosis in normal cats. 2. The ocular
      hypotensive and mitotic effects of Ha-118 were not observed in surgically
      sympathectomized cats indicating that an intact sympathetic pathway is necessary
      to demonstrate activity. 3. Ha-118 caused dose-dependent suppression of
      contractions of the cat nictitating membrane (CNM) elicited by electrical
      stimulation of the pre- and postganglionic sympathetic nerve trunks but not by
      exogenously administered noradrenaline suggesting that Ha-118 affected
      prejunctional but not ganglionic or postjunctional receptors. 4. Sulpiride
      antagonized Ha-118-induced inhibition of neuronally mediated contractions in the
      CNM suggesting an interaction at DA2 receptors. 5. Topical administration of Ha
      118 inhibited the rise in intraocular pressure induced by oral water loading in
      rabbits. 6. Topical pretreatment with metoclopramide, a DA2 antagonist, inhibited
      the ocular antihypertensive effect of Ha-118 in rabbits. 7. These studies
      demonstrate that Ha-118 decreased intraocular pressure (IOP) and pupil diameter
      (PD) in the cat and that this activity can be correlated with suppression of
      peripheral sympathetic tone in the CNM.

PMID- 1974257
TI  - Streptozotocin-diabetes attenuates alpha 2-adrenoceptor agonist-induced delay in
      small intestinal transit in mice.
AB  - 1. The effect of alpha 2-adrenoceptor agonists on gastrointestinal motility was
      assessed in normoglycaemic and streptozotocin-diabetic mice. 2. The alpha 2
      adrenoceptor agonists used were: clonidine (0.1, 0.3 and 1 mg kg-1, azepexole
      (10, 20 and 40 mg kg-1), tizanidine (1, 3 and 10 mg kg-1) and ST-91 (10, 20 and
      30 mg kg-1). 3. Acute hyperglycaemia was induced by D-(+)-glucose (5 g kg-1) and
      chronic hyperglycaemia by streptozotocin (200 mg kg-1) injection. 4. The gut
      motility was quantitated using the charcoal meal test. 5. The results indicate
      that in normoglycaemic and acutely hyperglycaemic mice, all of the alpha 2
      adrenoceptor agonists used produced significant inhibition of meal transit. 6.
      However, in streptozotocin-diabetic mice, the anti-transit effect of alpha 2
      adrenoceptor agonists was attenuated. 7. Since streptozotocin-induced diabetes
      but not acute hyperglycaemia was associated with the attenuation of anti-transit
      effect, elevated blood sugar is not the mechanism for the observed effect. 8. As
      with groups treated with clonidine, azepexole or tizanidine, the anti-transit
      effect of a peripherally acting alpha 2-adrenoceptor agonist, ST-91, was
      attenuated in streptozotocin-diabetic mice. This suggests the involvement of
      peripheral mechanism(s) in attenuating the anti-transit effect of alpha 2
      adrenoceptor agonists. 9. These results identify the need for critical evaluation
      of the role and efficacy of alpha 2-adrenoceptor agonists in the therapeutic
      management of diabetic diarrhoea.

PMID- 1974258
TI  - Molecular dissection of the NH2-terminal signal/anchor sequence of rat dipeptidyl
      peptidase IV.
AB  - Dipeptidyl peptidase IV (DPPIV) is a membrane glycoprotein with a type II
      orientation in the plasma membrane. As shown in a cell-free translation system,
      the amino-terminal 34 amino acids of rat DPPIV are involved in translocating
      nascent polypeptide across the membrane of microsomes and in anchoring the
      translocated polypeptide in the microsomal membrane. The amino-terminal sequence
      performing this dual function is composed of: a central hydrophobic core of 22
      amino acid residues; 6 amino-terminal residues preceding the hydrophobic core
      (MKTPWK); and 6 residues following the hydrophobic core. The six residues
      preceding the hydrophobic core are exposed on the outside (cytoplasmic side) of
      the microsomal membrane. Site-directed mutagenesis studies show that deletion of
      this cytoplasmic domain, excluding the amino-terminal initiating methionine, does
      not affect translocation of nascent DPPIV polypeptide, but does affect
      significantly anchoring of the translocated polypeptide in the microsomal
      membrane. In contrast, changing the two cytoplasmic Lys to Glu residues or
      shortening of the hydrophobic core from 22 to 15 residues or converting the last
      11e of the shortened hydrophobic core into Ala affects neither translocation
      across nor anchoring of the DPPIV polypeptide in the microsomal membrane. These
      and other structural features of the DPPIV amino-terminal signal-anchor sequences
      are discussed along with other types of sequences for their role in targeting
      nascent polypeptides to the RER.

PMID- 1974259
TI  - Suppression of protein kinase C and the stimulation of glucocorticoid receptor
      synthesis by dexamethasone in human fibroblasts derived from tumor tissue.
AB  - Exposure of fibroblasts derived from keloid tissues, desmoid and dermal tissue
      from individuals with Gardner's syndrome (GS) to dexamethasone resulted in the
      suppression of protein kinase C (PKC) activity and [3H]thymidine incorporation
      into DNA, and a 20-fold induction of glutamine synthetase activity. Treatment of
      GS and keloid fibroblasts with 0.1 microM dexamethasone for 36 h increased
      glucocorticoid receptor (GR) synthesis, as determined by [35S]methionine labeling
      and immunoprecipitation with a monoclonal antibody to the human GR. The
      suppression of PKC activity by dexamethasone was shown to result from a loss of
      protein mass as determined by immunoblotting using an antibody to PKC type III.
      In contrast to these results, exposure of fibroblasts isolated from normal
      tissues to dexamethasone did not result in the suppression PKC and [3H]thymidine
      incorporation, there was only a sixfold induction of glutamine synthetase, and a
      decrease of GR synthesis. As no primary receptor binding defect could be
      detected, the altered response of tumor cells to steroid-occupied receptor
      indicates a partial post-receptor binding defect in GS and keloid cells.

PMID- 1974260
TI  - Effect of hypertonic saline infusion on the level of immunoreactive dynorphin in
      extracted human plasma.
AB  - Dynorphin-A and its related peptides are derived from prodynorphin, one of the
      three known endogenous opioid precursors. The prodynorphin gene is expressed in
      the vasopressinergic magnocellular neurons of the hypothalamus, while its peptide
      products are present in the vasopressin (AVP) neurosecretory vesicles of the
      neurohypophysis. The concentration of immunoreactive (IR) dynorphin is orders of
      magnitude higher in the neurohypophysis than in any other tissue, suggesting that
      perhaps the prodynorphin-derived peptides are secreted from the hypothalamic
      neurohypophyseal unit into the general circulation. Experiments in rats have
      shown that osmotic stimuli increase both AVP and prodynorphin in the
      hypothalamus. To determine whether human hypothalamic prodynorphin is also under
      osmotic regulation, we measured plasma IR-dynorphin, plasma IR-AVP, and serum
      sodium immediately before and during the infusion of normal or hypertonic saline
      in normal human volunteers. Because of the unusual susceptibility of the
      prodynorphin-derived peptides to cleavage by endopeptidases, we also developed an
      appropriate plasma dynorphin extraction technique. We found that the IR-dynorphin
      present in human plasma was composed of 6K- and 4K-sized peptides and that no
      larger than 6K or smaller than 4K dynorphins were present. The infusion of normal
      saline did not have any significant effect on plasma IR-dynorphin, while 3%
      hypertonic saline increased its plasma levels. Thus, the mean IR-dynorphin level
      in the plasma of the volunteers infused with normal saline was 40.3 +/- 6.4
      fmol/mL (mean +/- SE; n = 6) at zero time; after 30 min of infusion, plasma IR
      dynorphin was 36.0 +/- 6.3, after 60 min it was 29.9 +/- 5, after 90 min it was
      36.0 +/- 4.7, after 120 min it was 36.8 +/- 3.2, and after 150 min it was 36.0 +/
      6.1. The plasma IR-dynorphin level in the volunteers infused with hypertonic
      saline was 31.7 +/- 3.5 fmol/mL (mean +/- SE; n = 10) at zero time. After 30 min
      of infusion it increased to 37.4 +/- 3.8, after 60 min to 46.4 +/- 7.7, after 90
      min to 56.2 +/- 9.1, after 120 min to 53.6 +/- 8.7, and after 150 min to 99.0 +/-
      14.2. The increase in plasma IR-dynorphin with time was significant (P less than
      0.0001) and correlated positively with serum sodium and plasma AVP. The
      physiological role of the prodynorphin-derived peptides of the hypothalamic
      neurohypophyseal unit is not yet known.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1974261
TI  - Decreased high affinity state in platelet alpha 2-adrenoceptors from diabetic
      patients with orthostatic hypotension.
AB  - Plasma catecholamine levels, total platelet alpha 2-adrenoceptor number and
      affinity state (using [3H]yohimbine binding) were investigated in insulin
      dependent diabetic patients with (n = 12) or without (n = 10) orthostatic
      hypotension due to autonomic neuropathy as well as in normal control subjects (n
      = 6). Mean resting basal catecholamine values were similar in the three groups.
      One-minute standing elicited an increase in norepinephrine plasma level (but not
      in epinephrine plasma levels) in control group but not in diabetic patients (with
      or without orthostatic hypotension). The maximal number of platelet alpha 2
      adrenoceptors (and KD) calculated by [3H]yohimbine saturation experiments was
      similar in the three groups. The percentage of platelet alpha 2-adrenoceptors in
      high affinity state (inhibition experiments of [3H]yohimbine by UK14,304, a
      specific alpha 2-adrenergic full agonist) was significantly lower in diabetic
      patients with orthostatic hypotension (29.2 +/- 5.3%) than in the other two
      groups. No significant difference was found between the control group (60.0 +/-
      2.0%) and diabetic patients without orthostatic hypotension (64.3 +/- 3.1%).
      Since platelet alpha 2-adrenoceptors are thought to be a suitable index of
      vascular alpha-adrenoceptors, the decrease in platelet alpha 2-adrenoceptors in
      high affinity state could explain the occurrence of orthostatic hypotension in
      insulin-dependent diabetic patients. Multiple pathophysiological mechanisms
      underly orthostatic hypotension in insulin-dependent diabetic patients and
      include anomalies both in the sympathetic nervous system and in alpha 2
      adrenoceptor coupling.

PMID- 1974262
TI  - Effects of a new prolactin inhibitor, CV 205-502, in the treatment of human
      macroprolactinomas.
AB  - The effects of a new PRL inhibitor, CV 205-502 (CV), on human macroprolactinomas
      were studied in nine patients according to a prospective protocol. Five patients
      had undergone surgery leaving tumor remnants and persistent hyperprolactinemia.
      The four others were de novo patients, two of whom had received short term
      treatment with Parlodel. Plasma PRL levels ranged from 235-6050 micrograms/L
      before treatment. The doses of CV used in this trial ranged from 0.075-0.600 mg.
      Plasma PRL normalized in eight of the nine patients during treatment with CV. The
      time to normalize varied from 2 weeks to 9 months, and the doses from 0.075-0.450
      mg. A tumor volume reduction of more than 50% was obtained in all four patients
      who had not been operated on before CV treatment. Only one of the five patients
      with postoperative tumor remnants had no reduction in tumor size. The drug was
      generally well tolerated, and no patient interrupted the treatment. Slight and
      short-lasting gastrointestinal symptoms were noted in several patients, and a
      single episode of fainting occurred in one patient when the drug was not taken at
      bedtime as instructed. A noticeable and persistent weight loss with anorexia was
      noted in two patients. Since CV 205-502, administered in a single daily dose, has
      tolerable side-effects and is effective in reducing PRL secretion and tumor size,
      it can be considered to be a useful treatment for macroprolactinomas.

PMID- 1974263
TI  - Characterization, by molecular cloning, of smaller forms of thyroid peroxidase
      messenger ribonucleic acid in human thyroid cells as alternatively spliced
      transcripts.
AB  - The mRNA for human thyroid peroxidase (hTPO) is 3.1 kilobases (kb) in size,
      coding for a protein of 933 amino acids. However, there is controversy as to
      whether other hTPO mRNA transcripts exist in thyroid cells. There is one report
      of the existence of 2.1- and 1.7-kb transcripts (hTPO mRNA species I and II),
      representing up to half of the hTPO mRNA in TSH-stimulated human thyroid cells.
      On the other hand, numerous other studies have only observed 3.1-kb hTPO mRNA
      transcripts. The nature of these putative 2.1- and 1.7-kb mRNA transcripts, if
      present, is unknown. We now report the isolation and characterization of two
      smaller hTPO cDNA species, designated hTPO cDNA I and II. cDNA I and II are 1753
      and 1044 basepairs (bp) in size, with open reading frames of only 225 and 174
      amino acids, respectively. Comparison of the nucleotide sequences of cDNA I and
      II with available hTPO genomic sequence reveals that cDNA I consists of exons 1-6
      (654 bp) and the 5'-end of intron 6 (1099 bp); cDNA II contains exons 1-5 (486
      bp) and an unidentified DNA tract of 558 bp further down-stream, presumably an
      intron. Confirmation that cDNA I and II correspond to mRNA transcripts I and II,
      respectively, was provided by Northern blot analysis with DNA probes specific for
      cDNA I and II. hTPO mRNA transcripts I and II are present in TSH-stimulated and
      TSH-deprived human thyroid cells in culture as well as in intact thyroid tissue.
      In summary, the present data 1) demonstrate directly that hTPO mRNA transcripts I
      and II exist in human thyroid cells, 2) explain the discrepant data in the
      literature regarding their existence, 3) elucidate their molecular structure, 4)
      indicate that they are generated by alternative splicing, and 5) demonstrate that
      hTPO mRNA I and II exist in the thyroid gland in vivo as well as in thyroid cells
      in culture.

PMID- 1974264
TI  - Normal and adenomatous human pituitaries secrete thyrotropin-releasing hormone in
      vitro: modulation by dopamine, haloperidol, and somatostatin.
AB  - TRH is present in human normal pituitaries and in pituitary adenomas. In this
      study we demonstrated that the same tissues can release TRH in vitro. Fragments
      from seven normal pituitaries (10-15 mg/syringe) and dispersed cells from eight
      prolactinomas, four GH-secreting and two nonsecreting adenomas (1-3 x 10(6)
      cells/syringe) were perifused using a Krebs-Ringer culture medium. After 1 h of
      equilibration the perifusion medium was collected every 2 min (1 mL/fraction) for
      3 h. TRH, PRL, and GH were measured by RIA under basal conditions and in the
      presence of 10(-10) to 10(-6) mol/L dopamine (DA), alone or concomitant with
      haloperidol, or in the presence of 10(-10) or 10(-6) mol/L somatostatin. Both
      normal pituitary fragments and pituitary adenomatous cells (from all types of
      adenomas studied) spontaneously released TRH in vitro. TRH was detected in the
      perifusion medium either immediately after the end of the equilibration period or
      30-60 min later. The molecular identity of TRH was assessed by high pressure
      liquid chromatography. There was no difference in the profile and the rate of TRH
      secretion between normal and tumoral tissues, and no correlation was found
      between the level of TRH release and that of PRL or GH secretion. DA stimulated
      TRH release from normal pituitaries and from PRL- and GH-secreting adenomas at
      doses as low as 10(-10) mol/L. A concomitant decrease in PRL and GH release was
      observed from adenomatous cells and in one case of normal tissue. Haloperidol
      (10(-7) mol/L) antagonized the effect of 10(-8) mol/L DA on both TRH and PRL
      secretion in normal pituitary and in prolactinomas. DA had no effect on TRH
      release from two nonsecreting tumors. The amounts of TRH released during 1 h of
      perifusion were 60-1640 pg/2 mg wet wt tissue in normal pituitaries and 54-2174
      pg/10(6) cells in adenomas; these values were very high compared to those
      precedently reported within the tissues. These results indicate that pituitary
      cells can release TRH in vitro and suggest that TRH might be synthesized in situ.
      We suggest that TRH could act on pituitary hormone secretion and/or cell
      proliferation via a paracrine and/or an autocrine mechanism.

PMID- 1974265
TI  - Rapid assessment of haemophilia A carrier state by non-invasive techniques using
      the polymerase chain reaction.
AB  - The polymerase chain reaction (PCR) was used to amplify two polymorphic regions
      in the factor VIII gene. In vitro synthesis of DNA was achieved using samples
      obtained from buccal cells, urine, and hair follicles in addition to purified
      genomic and crude DNA samples prepared from whole blood. Female members of two
      kindreds affected with haemophilia A were assessed for carrier state using direct
      restriction fragment length polymorphism analysis of amplified gene products in
      the Bc1I and XbaI regions. It is concluded that this is a non-invasive, rapid,
      and inexpensive technique for carrier detection.

PMID- 1974266
TI  - Expression of CD15 antigen in urinary bladder transitional cell carcinoma.
AB  - The biopsy specimens of 91 patients between the ages of 38 and 94 with
      transitional cell carcinoma of the bladder were retrospectively reviewed to
      determine if the expression of CD15 antigen detected by a monoclonal antibody MC2
      was correlated with prognosis. Expression was variable, ranging from strong
      expression of the antigen by only the superficial cells in well differentiated
      papillary lesions to weak expression by most cells in solid or invasive tumours.
      In the invasive component there was a correlation between MC2 expression and
      tumour type, suggesting that the cell surface carbohydrate detected by MC2 may
      have a role in cell adhesion. There was no correlation between staining and
      survival. It is concluded that tumour type, grade, and stage remain the best
      prognostic indicators of urothelial tumours.

PMID- 1974267
TI  - Radiologic evaluation of midfoot injuries: test of interpretation and clinical
      knowledge.

PMID- 1974268
TI  - Circulating somatostatin after oral glucose in hypothyroidism.
AB  - The response of circulating somatostatin-like immunoactivity (SLI) to oral
      glucose and its relation to other pancreatic islet cell hormones were studied in
      10 hypothyroid subjects before and after treatment. None of the patients suffered
      from diabetes mellitus or obesity. Compared with normal controls, the hypothyroid
      subjects had higher fasting and stimulated SLI levels but lower fasting
      pancreatic glucagon levels. Integrated glucose and insulin responses following
      glucose ingestion were normal, but the peak insulin response was delayed to 120
      min suggesting impaired pancreatic beta-cell response to oral glucose. On the
      other hand, the peak response of plasma C-peptide was higher probably because of
      a reduction in metabolic clearance. In both hypothyroid subjects and controls, a
      significant correlation was found between the maximal increment of SLI and the
      maximal decrement of glucagon following oral glucose. In conclusion, plasma SLI
      is increased in hypothyroidism. The changes in SLI may be due to either an
      increased hormonal secretion or a reduced metabolic clearance in hypothyroidism.
      This elevated SLI might contribute to the slower gastrointestinal motility
      observed in hypothyroidism. Our data also suggest that the reduction in glucagon
      secretion may be secondary to the increase in circulating SLI.

PMID- 1974269
TI  - Disappearance of thyroid-stimulation blocking antibody by glucocorticoid therapy
      in a patient with primary myxedema who developed aortitis syndrome during L
      thyroxine supplementation.
AB  - A 39-year-old woman with primary myxedema, who had the potent activities of
      thyrotropin-binding inhibitory immunoglobulins (TBII) and thyroid-stimulation
      blocking antibodies (TSBAb), developed aortitis syndrome about 6 months after the
      initiation of L-thyroxine (L-T4) supplementation. A 35 mg daily dose of
      prednisolone for aortitis syndrome was initiated, and the dose was gradually
      reduced. TBII and TSBAb activities were gradually decreased, and both reached
      normal levels (7.7% and 10.1%, respectively) 3 months after the initiation of
      prednisolone. Therefore, dose of L-T4 was gradually reduced, and L-T4
      supplementation was stopped. Subsequently, however, recurrence of hypothyroidism
      was not observed. These observations indicate the possibility that hypothyroidism
      remits with disappearance of TBII and TSBAb activities in not only neonatal cases
      but also adult cases.

PMID- 1974270
TI  - Osteocalcin levels in patients with microprolactinoma before and during medical
      treatment.
AB  - Osteocalcin (OC) concentration, a specific index of bone formation, was measured
      in 29 female patients with microprolactinoma (serum prolactin, PRL: 105 +/- 10.9
      ng/ml; mean +/- SE). Mean OC levels were significantly lower than in controls
      (1.7 +/- 0.2 vs 5.1 +/- 0.3 ng/ml; p less than 0.001), being below the normal
      range in 28 out of 29 patients. All patients were treated with dopaminergic
      agents (dihydroergocriptine, bromocriptine or cabergoline). After treatment mean
      serum PRL levels were significantly reduced (12 +/- 3.1 ng/ml; p less than
      0.001), a full normalization being obtained in 26 patients. There were no
      significant differences in both basal and after treatment PRL levels among
      patients treated with different drugs, although a greater PRL decrease was
      induced by cabergoline. Serum OC levels significantly increased after 12 month
      therapy (4.7 +/- 0.6 ng/ml, p less than 0.001), a normal concentration being
      reached in 14 of 29 cases. During treatment there were no significant differences
      in serum estradiol and PRL concentrations between patients who normalized or not
      their OC levels, while the reduction in PRL levels with respect to baseline was
      more pronounced in the former group. The absolute increase in OC levels
      positively correlated with serum PRL decrements (p less than 0.01). It is
      noteworthy that serum OC normalized in 1/10 patients during dihydroergocriptine,
      3/8 during bromocriptine and 10/11 during cabergoline. Four patients, previously
      treated with dihydroergocriptine and bromocriptine without normalizing OC and PRL
      levels, underwent a second course of therapy with cabergoline and then normalized
      OC concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1974271
TI  - Pharmacokinetics of remoxipride controlled release and immediate release capsules
      in schizophrenic patients.
AB  - Single dose and steady-state pharmacokinetics of remoxipride, a new antipsychotic
      drug, were compared after administration of a controlled release capsule (CR) and
      an immediate release capsule (IR), both 200 mg and administered b.i.d. Thirteen
      patients with chronic schizophrenia entered the double-blind 6-week crossover
      study. Seven were evaluable for investigation of steady-state pharmacokinetics.
      Fluctuations in plasma remoxipride concentrations decreased considerably after
      remoxipride CR compared with the IR formulation. The plasma peak concentrations
      were significantly decreased and the trough values were increased after the CR
      formulation, although the average concentrations at steady-state were similar.
      The two formulations were bioequivalent regarding the amount of remoxipride
      absorbed after repeated dosing. Five out of 13 patients withdrew prematurely from
      the study because of ineffectiveness or refusal of treatment. Both formulations
      were well tolerated.

PMID- 1974272
TI  - Lymphocyte-mediated activation of cultured endothelial cells (EC). CD4+ T cells
      inhibit EC class II MHC expression despite secreting IFN-gamma and increasing EC
      class I MHC and intercellular adhesion molecule-1 expression.
AB  - Endothelial cells (EC) were cocultured with allogeneic PBL, CD4+ T cells, or CD8+
      T cells, and the degrees of EC activation induced examined by determining
      patterns of endothelial class I and class II MHC and intercellular adhesion
      molecule-1 (ICAM-1) expression. Coculture with PBL or CD8+ T cells uniformly
      increases class I MHC and ICAM-1 expression on all EC within a culture, but
      induces class II MHC expression on only a subpopulation(s) of EC. This
      heterogeneous EC response to coculture contrasts with the uniform class II
      expression on all EC induced by IFN-gamma in replicate wells. CD4+ T cells, when
      compared to equal numbers of unfractionated PBL or CD8+ T cells, are more
      effective at increasing class I MHC and ICAM-1 but are unable to induce class II
      MHC expression. The failure of CD4+ T cells to induce EC class II MHC Ag is not
      due to insufficient activation of the T cells, as PHA-activated CD4+ T cells also
      do not induce significant class II expression. In addition, conditioned media
      (CM) from CD4+ T cell/EC contain greater levels of immunoreactive IFN-gamma than
      do CM from PBL/EC cocultures. Rather, CD4+ T cells appear to actively inhibit the
      induction of EC class II Ag but not class I or ICAM-1 by IFN-gamma. Inhibition
      occurs at the time of induction, as CD4+ T cells are not capable of down
      regulating previously induced class II Ag. CM from CD4+/EC (but not PBL/EC)
      cocultures also inhibits IFN-gamma induction of EC class II MHC expression. The
      inhibitory activity is generated during CD4+ T cell-EC cell contact, and is
      enhanced by PHA. The inhibitory activity(ies) of the CD4+/EC-CM is as yet
      unidentified, and is only minimally reversible by cocktails of neutralizing
      antibodies directed against TNF-alpha, TNF-beta (lymphotoxin), IFN-alpha and IFN
      beta. In conclusion, CD4+ and CD8+ T cells are each effective activators of EC,
      but the patterns of activation produced by these subsets are quite distinct,
      largely due to generation of a soluble inhibitor(s) of class II MHC induction
      during coculture of CD4+ T cells with EC.

PMID- 1974274
TI  - Role of CD4+ T cells and T-independent mechanisms in acquired resistance to
      Salmonella typhimurium infection.
AB  - Two aspects of acquired resistance to Salmonella typhimurium infection in BALB/c
      mice, i.e., the ability to clear the primary inoculum from the spleen and
      resistance to a secondary challenge, were studied with the use of mAb against T
      cell subsets. The ability to clear a temperature-sensitive mutant of S.
      typhimurium from the spleen (assessed at day 21) was abrogated by in vivo
      treatment with anti-CD4 mAb. Accelerated bacterial clearance could be adoptively
      transferred into naive mice. In vitro depletion experiments also showed the role
      of CD4+ T cells in this phenomenon. Depletion of CD8+ T cells had only a marginal
      effect. Resistance to reinfection in the late phase of the primary infection (day
      50) was markedly depressed by in vivo treatment with anti-CD4 mAb, whereas this
      was not the case during the early phase (day 14). Furthermore, during the early
      phase of infection athymic nude mice showed increased nonspecific resistance to
      reinfection. Taken together these results suggest that T-independent mechanisms
      play a major role in acquired resistance during the early phase of infection.

PMID- 1974273
TI  - Activation of CD4+ lymphocytes by syngeneic brain microvascular smooth muscle
      cells.
AB  - Splenocyte proliferation as measured by [3H]thymidine incorporation was detected
      when brain microvessel smooth muscle cells (SM) were cocultured with syngeneic
      spleen cells. This report focuses on the role of different lymphocyte populations
      in this activation. The central role of CD4+ T cells in the proliferation
      response has been established by different sets of experiments. The phenotypic
      characterization of splenic lymphocytes before and after the co-culture showed
      that the only cell type present in higher number after the co-culture than before
      is the CD4+ T cell. When CD4+ cells were purified by flow microfluorimetry and co
      cultured with SM a strong proliferative response was detected. In contrast,
      purified CD8+ cells in co-culture with SM cells did not proliferate. The
      activation of CD4+ cells by SM required direct cell-to-cell contact and could be
      detected on the fourth day, reaching maximal levels at the 6th and 7th days of
      the co-culture. The activation is more pronounced in the syngeneic system than
      under allogeneic conditions and is inhibited by anti-MHC II mAb, but not by anti
      MHC II mAb. The finding that vascular smooth muscle cells can activate syngeneic
      T cells may have important implications concerning the mechanism of induction of
      vasculitis.

PMID- 1974275
TI  - Tumor necrosis factor beta and ultraviolet radiation are potent regulators of
      human keratinocyte ICAM-1 expression.
AB  - Intercellular adhesion molecule-1 (ICAM-1) functions as a ligand of leukocyte
      function-associated antigen-1 (LFA-1), as well as a receptor for human picorna
      virus, and its regulation thus affects various immunologic and inflammatory
      reactions. The weak, constitutive ICAM-1 expression on human keratinocytes (KC)
      can be up-regulated by cytokines such as interferon-gamma (IFN gamma) and tumor
      necrosis factor alpha (TNF alpha). In order to further examine the regulation of
      KC ICAM-1 expression, normal human KC or epidermoid carcinoma cells (KB) were
      incubated with different cytokines and/or exposed to ultraviolet (UV) radiation.
      Subsequently, ICAM-1 expression was monitored cytofluorometrically using a
      monoclonal anti-ICAM-1 antibody. Stimulation of cells with recombinant human (rh)
      interleukin (IL) 1 alpha, rhIL-4, rhIL-5, rhIL-6, rh granulocyte/macrophage
      colony-stimulating factor (GM-CSF), rh interferon alpha (rhIFN alpha), and rh
      transforming growth factor beta (TGF beta) did not increase ICAM-1 surface
      expression. In contrast, rhTNF beta significantly up-regulated ICAM-1 expression
      in a time- and dose-dependent manner. Moreover, the combination of rhTNF beta
      with rhIFN gamma increased the percentage of ICAM-1-positive KC synergistically.
      This stimulatory effect of rhTNF beta was further confirmed by the demonstration
      that rhTNF beta was capable of markedly enhancing ICAM-1 mRNA expression in KC.
      Finally, exposure of KC in vitro to sublethal doses of UV radiation (0-100 J/m2)
      prior to cytokine (rhIFN tau, rhTNF alpha, rhTNF beta) stimulation inhibited ICAM
      1 up-regulation in a dose-dependent fashion. These studies identify TNF beta and
      UV light as potent regulators of KC ICAM-1 expression, which may influence both
      attachment and detachment of leukocytes and possibly viruses to KC.

PMID- 1974276
TI  - Ultraviolet radiation can either suppress or induce expression of intercellular
      adhesion molecule 1 (ICAM-1) on the surface of cultured human keratinocytes.
AB  - Interactions of the ligand/receptor pair LFA-1(CD11a/CD18) and ICAM-1(CD54)
      initiate and control the cell-cell interactions of leukocytes and interactions of
      leukocytes with parenchymal cells in all phases of the immune response. Induction
      of the intercellular adhesion molecule 1 (ICAM-1) on the surface of epidermal
      keratinocytes has been proposed as an important regulator of contact-dependent
      aspects of cutaneous inflammation. Ultraviolet radiation (UVR) also modifies
      cutaneous inflammation, producing both up- and down-regulation of contact
      hypersensitivity. We have found that UVR has a biphasic effect on the induction
      of keratinocyte CD54. Using immunofluorescence and FACS techniques to quantitate
      cell-surface CD54 staining, we have shown that UVR (100 mJ/cm2 of UVB)
      significantly (p less than 0.01) inhibits keratinocyte CD54 induction by gamma
      interferon 24 h after irradiation. However, at 48, 72, and 96 h after UVR (10 to
      100 mJ/cm2), CD54 expression is significantly induced (p less than 0.01 to p less
      than 0.001) to levels even greater than are induced by gamma interferon (20
      U/ml). In addition, at 48, 72, or 96 h following UVR (30-100 mJ/cm2), the gamma
      interferon-induced CD54 expression on human keratinocytes is also strongly (p
      less than 0.05 to p less than 0.001) enhanced. In this cell-culture system, gamma
      interferon and TNF-alpha are both strong CD54 inducers and are synergistic, but
      GM-CSF, TFG-beta, and IL-1 have no direct CD54-inducing effects. Thus the effects
      of UVR on CD54 induction are biphasic, producing inhibition at 24 h and induction
      at 48, 72, and 96 h. This effect on CD54 may contribute to the biphasic effects
      of UVR on delayed hypersensitivity in vivo. The early inhibition of ICAM-1 by UVR
      may also contribute to the therapeutic effects of UVR. We also speculate that the
      late induction of ICAM-1 by UVR might be an important step in the induction of
      photosensitive diseases such as lupus erythematosus.

PMID- 1974277
TI  - An HLA class II region restriction fragment length polymorphism (RFLP) in
      patients with dermatitis herpetiformis: association with HLA-DP phenotype.
AB  - Dermatitis herpetiformis (DH) is characterized in part by an associated gluten
      sensitive enteropathy (GSE), and a strong association with the HLA antigens HLA
      A1, -B8, -DR3, and -DQw2, essentially identical to that seen in patients with
      isolated GSE (celiac disease). A 4.0-kb RsaI RFLP has been identified using a DQ
      beta-chain cDNA and localized to the HLA-DP beta-chain region. This RFLP has been
      found more frequently in patients with isolated GSE than in normal HLA matched
      controls. We have analyzed genomic DNA from 24 patients with DH and 15 HLA
      matched controls to determine if this 4.0-kb RsaI RFLP was present in patients
      with DH. Twenty-one of 24 (87%) of patients with DH were found to have this RFLP
      as compared to 7 of 10 (70%) HLA-DR3, -DQw2 matched control subjects (p = 0.23).
      Thus, the 4.0-kb RsaI RFLP detected in patients with isolated GSE is also present
      in patients with DH; however, its frequency in DH patients does not differ
      significantly from that of HLA matched controls. Family studies of patients with
      DH revealed that although the 4.0-kb RsaI RFLP segregated with the HLA-A1, -B8, 
      DR3, -DQw2 haplotype in one family, it did not segregate with this disease
      associated haplotype in two other families. In both patient and control
      populations, this RFLP was associated with HLA-DPw1 or -DPw3 phenotypes; 25 of 26
      (96%) HLA-DPw1 or -DPw3 subjects were found to have this RFLP compared to only 1
      of 6 (17%) who did not express HLA-DPw1 or -DPw3 (pc = 0.0009). These population
      and family data suggest that this 4.0-kb RsaI RFLP is primarily associated with
      the HLA-DPw1, -DPw3 phenotype, rather than the clinical manifestations of DH.
      These data further document that the strongest association of DH with HLA
      antigens remains with HLA-DQw2 and HLA-DR3 antigens.

PMID- 1974278
TI  - Modulation of melanocyte intercellular adhesion molecule-1 by immune cytokines.
AB  - Human melanocyte expression of intercellular adhesion molecule-1 (ICAM-1) with or
      without stimulation by interferon gamma (IFN-G), tumor necrosis factor alpha (TNF
      alpha), or interleukin-1-alpha (IL-1 alpha), was measured utilizing direct
      immunofluorescence and fluorescence-activated cell sorting (FACS). Melanocytes
      grown in vitro expressed low levels of ICAM-1, which could be increased by
      exposing the cells to IFN-G, TNF-alpha, or IL-1 alpha. Each cytokine caused an
      enhancement of melanocyte ICAM-1 expression in a dose-dependent fashion. The
      lowest dose necessary to cause a significant increase in melanocyte ICAM-1
      expression was 1 U/ml IFN-G, 0.3 ng/ml TNF-alpha, or 3 U/ml IL-1 alpha.
      Melanocytes were most sensitive to TNF-alpha stimulation, with the greatest
      levels of ICAM-1 expression following 30 ng/ml or more TNF-alpha. When IFN-G was
      added to melanocyte cultures in combination with TNF-alpha or IL-1 alpha, there
      was an additive increase in ICAM-1 expression but no synergy was noted with the
      combined cytokines. To our knowledge, this is the first report of melanocyte ICAM
      1 induction by TNF-alpha and IL-1 alpha and by physiologically relevant doses of
      IFN-G. Because of the importance of ICAM-1 in the regulation of immune cell
      target interactions, the study of ICAM-1 expression by melanocytes may help us to
      better understand immune mechanisms of melanocyte injury.

PMID- 1974279
TI  - Differential expression of lymphocyte function-associated antigen 1 (LFA-1) on
      epidermotropic and non-epidermotropic T-cell clones.

PMID- 1974280
TI  - Pyrimidine biosynthetic pathway of Pseudomonas fluorescens.
AB  - Pyrimidine biosynthesis in Pseudomonas fluorescens strain A126 was investigated.
      In this study, de novo pyrimidine biosynthetic pathway mutant strains were
      isolated using both conventional mutagenesis and transposon mutagenesis. The
      resulting mutant strains were deficient for either aspartate transcarbamoylase,
      dihydroorotase or orotate phosphoribosyltransferase activity. Uracil, uridine or
      cytosine could support the growth of every mutant strain selected. In addition,
      the aspartate transcarbamoylase mutant strains could utilize orotic acid to
      sustain their growth while the orotidine-5'-monophosphate decarboxylase mutant
      strains grew slowly upon uridine 5'-monophosphate. The wild-type strain and the
      mutant strains were used to study possible regulation of de novo pyrimidine
      biosynthesis in P. fluorescens. Dihydroorotase specific activity more than
      doubled after the wild-type cells were grown in orotic acid relative to
      unsupplemented minimal-medium-grown cells. Starving the mutant strains of
      pyrimidines also influenced the levels of several de novo pyrimidine biosynthetic
      pathway enzyme activities.

PMID- 1974281
TI  - Growth-rate-dependent synthesis of K99 fimbrial subunits is regulated at the
      level of transcription.
AB  - Increase in the production of the fimbrial adhesion K99 by enterotoxigenic
      Escherichia coli in continuous cultures at specific growth rates above 0.25 h-1
      was shown to be independent of the nature of the growth-limiting nutrient. The
      correlation between specific growth rate and K99 production was also found to be
      independent of the copy number of the K99 operon. Introduction of additional
      copies of the K99 regulatory region did not affect growth-rate-dependent K99
      production in wild-type strains, indicating that no hypothetical regulatory host
      factor is titrated by the K99 regulatory region. Regulation at the
      transcriptional level was measured with galactokinase gene fusions. The
      transcription of the fimbrial subunit gene increased with an increase in specific
      growth rate. This growth-rate-dependent transcription was found to originate from
      the strong promoter PA. Transcription originating from the weaker promoter PB was
      independent of growth rate. The results indicated that transcriptional regulation
      at PA is involved in the growth-rate-dependent regulation of K99 production.

PMID- 1974282
TI  - Management of focal intracranial infections: is medical treatment better than
      surgery?
AB  - Three groups of patients with single hemispheric brain abscesses or subdural
      empyemas, from 1 to 5 cm large, with similar initial prognosis, have been treated
      either by medical treatment alone (20), aspiration (21), or excision (15).
      Differences in survival were not found, but medical treatment alone was better
      for long term sequelae. Surgical procedures (either aspiration or excision) were
      better for both isolation of the organism and the hospital stay before discharge.
      In spite of good results, it is unwise to conclude too strongly in favour of no
      surgical treatment as this study was not randomised.

PMID- 1974283
TI  - Neuroleptic malignant syndrome.
AB  - Five patients with neuroleptic malignant syndrome (NMS) are described. The
      syndrome developed earlier and took longer to resolve in patients with
      schizophrenic disorders. Deterioration in the level of consciousness presented
      earlier than rigidity and fever in all five patients and was thus considered a
      major criterion. A significant proportion of the patients showed abnormalities of
      gaze. In four of the five patients spontaneous recovery occurred without the need
      for specific drugs.

PMID- 1974284
TI  - Effect of dietary blackcurrant seed oil on mouse macrophage subclasses of choline
      and ethanolamine glycerophospholipids.
AB  - There have been reports that dietary gamma-linolenic acid [18:3(n-6)] and alpha
      linolenic acid [18:3(n-3)] are capable of regulating cellular eicosanoid
      biosynthesis and inflammation. Because the eicosanoid cascade is regulated in
      part by the distribution of arachidonic acid [20:4(n-6)] among phospholipid
      subclasses, the effects of feeding blackcurrant seed oil [containing 18:3(n-6)
      and 18:3(n-3)] on the fatty acid composition of diacyl, alkylacyl and alkenylacyl
      subclasses of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were
      studied in mouse peritoneal macrophages. After 4 wk of dietary treatment, the
      relative distribution (mol %) of macrophage phospholipid classes and subclasses
      was not altered in animals fed blackcurrant seed oil relative to those fed corn
      oil [containing linoleic acid, 18:2(n-6)]. Macrophages from blackcurrant seed oil
      fed animals had reduced levels of PC diacyl 18:3(n-6), 18:3(n-3), 20:3(n-6),
      22:5(n-3), and alkylacyl 20:3(n-6), 22:5(n-3) and 22:6(n-3). In general, dietary
      blackcurrant treatment produced fatty acid alterations in PE subclasses that were
      similar to those in PC. A major exception, however, was the reduction in 20:4(n
      6) levels in all PE subclasses, whereas no effect in PC subclass 20:4(n-6) levels
      was noted. These findings indicate i) that pronounced differences in the
      polyunsaturated fatty acid (PUFA) compositions of macrophage PC and PE subclasses
      exist following dietary fat manipulation and ii) that 18:3(n-6) and 18:3(n-3)
      feeding can increase potential anti-flammatory precursor levels of 20:3(n-6) and
      (n-3) PUFA in the macrophage.

PMID- 1974285
TI  - Peptic ulcer in children.
AB  - From January 1983 to April 1989, 39 children were diagnosed as suffering from
      primary peptic ulcer. Of these ulcers, 30 were duodenal, seven prepyloric, and
      two patients had a combination of both. Among 36 patients with H2-blocker
      therapy, 33 had treatment completed with ulcer healing assessed by endoscopic
      examinations. Sixteen patients (49%) had ulcer healing within a single 6-week
      course of treatment, whereas 17 patients (51%) required multiple 6-week courses.
      The latter group had a mean basal acid output (BAO) of 0.13 +/- 0.06 mmol/kg/h
      and a mean maximal acid output (MAO) of 0.48 +/- 0.12 mmol/kg/h, which is
      significantly higher (P less than .05 and P less than .005, respectively) than
      the mean BAO (0.08 +/- 0.06 mmol/kg/h) and mean MAO (0.31 +/- 0.11 mmol/kg/h) in
      patients whose ulcers healed within 6 weeks of treatment. Subsequent follow-up
      with endoscopy over a mean period of 1.8 years (range, 3 months to 6 years)
      showed 10 patients with recurrent ulcers. Life-table analysis showed a recurrence
      rate of 35% within 1 year after ulcer healing. Five patients required surgery for
      ulcer complications--obstruction (2), perforation (2), and bleeding (1). In two
      of these patients initial H2-blocker therapy was unsuccessful.

PMID- 1974286
TI  - Posthatch day/night differences in synaptic ribbon populations of the chick
      pineal.
AB  - Pineal synaptic ribbon (SR) populations of the early posthatch white leghorn
      chick were counted to determine if they demonstrate a rhythm that is in
      accordance with the light/dark cycle. SRs were counted between day 7 and day 10
      and on day 14 of posthatch development, with samples at midlight, middark
      (14L:10D), and constant darkness. SR populations did not exhibit significant
      changes on days 7 and 8 under cycled lighting conditions nor on days 9 and 10
      under constant darkness. A second experiment demonstrated that the dark:light
      ratio of SR populations of day 14 chicks, under cycled lighting, was 3.4:1.0,
      indicating SR rhythmicity by that stage of development. In that a preliminary
      experiment had demonstrated a 4.2:1.0 dark:light ratio in SR populations in a
      predominantly day-10 population of chicks, we believe that SR rhythmicity begins
      on, or near, day 10 of posthatch development. To determine if the invasion of
      sympathetic fibers from the superior cervical ganglion (SCG) correlates with the
      initiation of SR light/dark population differences, we employed tyrosine
      hydroxylase immunofluorescence to reveal the distribution of catecholaminergic
      fibers in chick pineal follicles. Follicular innervation doubled over the day 7
      to day 14 period, during which time light/dark differences in SR populations were
      established. There is a correlation, in time, between the invasion of the pineal
      by the sympathetic fibers and the initiation of SR light/dark differences. The
      circadian rhythm of pineal N-acetyltransferase (NAT) activity, the rate-limiting
      enzyme in the melatonin pathway, is established earlier (day 2) than the
      light/dark differences in SR populations (day 10). It is possible that SR
      rhythmicity is influenced by the ingrowth of the pineal sympathetic innervation,
      and that SRs respond to an extrapineal oscillator rather than the independent
      oscillators of the chick pineal responsible for the rhythm of NAT activity and
      melatonin synthesis.

PMID- 1974287
TI  - Electrophoretic study of nitrofurantoin in aqueous suspensions. Effect of the
      addition of a polymeric thickener.
AB  - The electrophoretic mobility of nitrofurantoin (based on the microelectrophoresis
      method) has been studied in dilute dispersions of the drug. Specifically, the
      effect of NaCl, CaCl2 and AlCl3, pH, and a thickener, Carbopol 934, was
      determined. The electrophoretic mobility (mu) increases in absolute terms when
      the pH is raised between 3 and 9, although mu remains negative in this pH range.
      The variation of absolute mobility ([mu[) with NaCl concentration shows a
      pronounced maximum for a concentration of about 10(-4) M. However, when the
      concentration of CaCl2 in the medium is increased, [mu[ decreases steadily. The
      effect of AlCl3 concentration on the mobility is markedly influenced by the pH of
      the dispersing medium although a general trend is observed for mu to become more
      positive with increasing concentration of the salt. Finally, Carbopol 934 appears
      to impart an extra negative charge to the nitrofurantoin surface, since higher
      negative mobilities were measured in the presence of the polymer.

PMID- 1974288
TI  - Evidence for more than one binding site for sulfonylureas in insulin-secreting
      cells.
AB  - Specific binding of both [3H]glibenclamide and [3H]gliquidone has been observed
      in a particulate fraction of insulin-secreting rat tumour (RIN m5F) cells. The
      binding of both the labels was time-dependent, of high affinity (including a low
      affinity binding site), saturable and reversible. The rank order of inhibition of
      [3H]glibenclamide binding was glibenclamide greater than gliquidone greater than
      AG-EE 388 = AG-EE 86 = AG-EE 319 greater than AG-EE 436 (AG coded drugs are
      benzoic acid derivatives which lack the sulfonylurea moiety of sulfonylureas).
      The Kds of high affinity binding for glibenclamide and gliquidone were 0.08 and
      1.3 nM, respectively. When [3H]gliquidone was used as the labelled compound this
      rank order of binding and the affinities of drugs were different, e.g.
      glibenclamide was less potent than gliquidone. The Kd values of high affinity
      binding to the [3H]gliquidone binding site were 810 and 79 nM with respect to
      glibenclamide and gliquidone. The binding site labelled by [3H]gliquidone, in
      contrast to that labelled by [3H]glibenclamide, was not able to discriminate
      between the two enantiomers AG-EE 319 and AG-EE 436. The data indicate that there
      are different binding sites for glibenclamide and gliquidone in RIN m5F cells. In
      extension to data of other groups it is speculated that there exists more than
      one specific binding site for sulfonylureas and other related compounds, e.g.
      benzoic acid derivatives and that sulfonylureas behave differently not only in
      quantitative but in qualitative terms as well.

PMID- 1974289
TI  - Inhibitory effect of HSR-6071, a new anti-allergic agent, on experimental asthma
      in rats and guinea-pigs.
AB  - The experimental asthma caused by IgE antibody in rats was inhibited by HSR-6071
      (6-(1-pyrrolidinyl)-N-(1H-tetrazol-5-yl)-2-pyrazinecarboxamide) (0.01-0.1 mg kg-1
      i.v.) in a dose-dependent manner. The inhibitory activity of HSR-6071 was more
      potent than those of disodium cromoglycate and ketotifen, and equipotent with
      amlexanox. The bronchoconstriction mediated by IgE or IgG antibody in guinea-pigs
      was also prevented by HSR-6071 (0.3, 1 and 3 mg kg-1 i.v.), amlexanox (3, 10 and
      30 mg kg-1 i.v.) and ketotifen (0.1 mg kg-1 i.v.) but not by disodium
      cromoglycate (10 mg kg-1 i.v.). HSR-6071 was more potent than amlexanox, but less
      potent than ketotifen. HSR-6071 suppressed antigen-induced histamine and SRS-A
      release from minced lung tissues of guinea-pigs sensitized passively with rabbit
      anti-EA serum and was a more potent inhibitor of the release of SRS-A than of
      histamine. On the other hand, histamine- or acetylcholine-induced
      bronchoconstriction in guinea-pigs was scarcely affected by HSR-6071 at doses
      sufficient to inhibit the experimental asthma, but LTD4-induced
      bronchoconstriction was dramatically inhibited. These results indicate that the
      inhibitory action on experimental allergic asthma of HSR-6071 may be due to
      suppression of antigen-induced histamine and SRS-A release from lung tissues and
      to antagonism of SRS-A action. In addition, HSR-6071 inhibited cyclic AMP
      phosphodiesterase activity and produced relaxation of the guinea-pig isolated
      trachea. These pharmacological actions may contribute to the production of the
      anti-allergic action of HSR-6071.

PMID- 1974290
TI  - Pharmacokinetics, bioavailability, metabolism, tissue distribution and urinary
      excretion of gamma-L-glutamyl-L-dopa in the rat.
AB  - gamma-L-Glutamyl-L-dopa (gludopa) is believed to be a dopamine prodrug specific
      for the kidney. Its pharmacokinetics have been studied in the rat given 50 mg kg
      1 intravenously (i.v.) and 60 mg kg-1 intraperitoneally (i.p.). By the i.v.
      route, elimination followed apparent first order kinetics and was biphasic with a
      t 1/2 alpha of 7 min and terminal half-life of 67 min. After i.p. administration
      absorption was rapid (t 1/2 ab 6 min), elimination was monophasic with a terminal
      half-life almost identical following i.v. dosing (65 min), and bioavailability
      was 40%. In tissues (liver and kidney) gludopa was biotransformed to four intact
      catecholic products (L-dopa, dopamine, DOPAC and gamma-L-glutamyl-dopamine) which
      appeared quickly (peaks at 15 min) and which were almost completely cleared by 4
      h. Dopamine was the major kidney metabolite accounting for 69% of total catechol
      content with an AUC 31 times greater than in liver where it accounted for only
      34% of total catechols. In rat urine eight major metabolites (5.7% of the dose)
      and at least 12 minor metabolites were detected of all of which 85% was dopamine.
      A higher percentage of the dose was excreted as intact catechols in man (15.7%)
      but fewer metabolites were detected (L-dopa, dopamine, DOPAC). It is confirmed
      that gludopa is kidney specific in rat but that the pharmacological effects of
      dopamine are likely to be short lived due to rapid clearance. Gludopa appears to
      be less dopamine specific in man.

PMID- 1974291
TI  - On the use of diazepam and pro-diazepam (2-benzoyl-4-chloro-N-methyl-N
      lysylglycin anilide), as adjunct antidotes in the treatment of organophosphorus
      intoxication in the guinea-pig.
AB  - Diazepam and pro-diazepam (2-benzoyl-4-chloro-N-methyl-N-lysylglycin anilide)
      have been used as adjunct antidotes to pyridostigmine and atropine against the
      organophosphate, soman, in the guinea-pig. Both added significant protection to
      the pyridostigmine/atropine treatment. Animals pretreated with diazepam, 60 min
      before soman, were "better" protected than animals given an equimolar dose of pro
      diazepam therapeutically 1 min after soman. A pretreatment with diazepam for
      three days further increased the protection. A therapeutic dose of pro-diazepam,
      1 min after soman, gave no further protection, to the three day diazepam
      pretreatment. The serum concentrations of diazepam (given i.p.) and
      desmethyldiazepam (given i.m.) were determined by GLC after diazepam (i.p.) and
      pro-diazepam (i.m.) were given. The protection, relative to the control, provided
      by the diazepam pretreatment (60 min before and for three days before soman)
      correlated linearly, r = 0.9898, with the serum values of diazepam achieved at
      these times. Our data suggest that diazepam as adjunct to pyridostigmine and
      atropine administered as pretreatment gives a "safer" protection, than an
      equimolar dose of pro-diazepam given therapeutically.

PMID- 1974292
TI  - Zinc acexamate inhibits gastric acid and pepsinogen secretion in the rat.
AB  - Pretreatment with zinc acexamate (25-100 mg kg-1 i.p.) inhibited acid and
      pepsinogen secretion in the pylorus-ligated rat. Zinc acexamate (5-50 mg kg-1
      p.o.) also inhibited the increases in acid secretion induced by carbachol (10
      micrograms kg-1) and 2-deoxy-D-glucose (200 mg kg-1) in the perfused stomach of
      the anaesthetized rat. A delayed antisecretory effect was observed with this drug
      on histamine induced responses. High concentrations of zinc acexamate (10(-5) -
      10(-2) M) did not modify the in-vitro activity of pepsin. Administration of zinc
      acexamate resulted in an increase in the presence of pepsinogen at the mucosal
      level. A morphological examination of the gastric mucosa confirmed an
      accumulation of zymogen-containing granules in the gastric chief cells of zinc
      acexamate-treated rats (50 mg kg-1 p.o.). These results indicate that zinc
      acexamate decreases acid and pepsinogen secretion in-vivo, and this may explain
      its antiulcer activity.

PMID- 1974293
TI  - A comparison of the effects of nicotine and (+)-amphetamine on rat behaviour in
      an unsignalled Sidman avoidance schedule.
AB  - In agreement with the results of previous studies, the withdrawal of nicotine
      from rats trained on an unsignalled Sidman avoidance schedule under the influence
      of the drug (0.4 mg kg-1 given subcutaneously 3 min before each training session)
      was associated with a reduction in lever-pressing responses (P less than 0.05)
      and an increase in the number of shocks received (P less than 0.01). The number
      of shocks received by the withdrawn rats was also greater (P less than 0.05) than
      the number of shocks received by rats trained and tested with saline, whereas the
      number of lever-pressing responses recorded for saline-treated rats was not
      influenced significantly by the drug used during training. The subcutaneous
      administration of (+)-amphetamine (0.5 mg kg-1 30 min before the test session)
      stimulated lever-pressing in rats trained with saline or nicotine and abolished
      the increase in the number of shocks received by the nicotine-withdrawn rats, but
      had no significant effect on the number of shocks received by rats trained with
      saline. The number of shocks received by the rats trained on the schedule with
      (+)-amphetamine but tested after an injection of saline was also greater (P less
      than 0.05) than the number of shocks received by rats trained and tested with
      saline. It is concluded that the disruption in shock avoidance performance
      observed for the nicotine- and (+)-amphetamine-withdrawn rats may reflect the
      development of dependence upon the stimulant properties of these drugs.

PMID- 1974294
TI  - Detection of poly(I):poly(C12U), mismatched double-stranded RNA, by rapid
      solution hybridization: blood values after intravenous infusion.
AB  - A rapid solution hybridization technique has been developed for estimating blood
      concentrations of poly(I):poly(C12U), a high molecular weight bioactive double
      stranded RNA. Samples were prepared by mixing 100 microL of blood with, 165
      microL of 6 M guanidine thiocyanate (GuSCN) and 0.16 M EDTA pH 8.0, and freezing.
      Hybridizations were carried out with a [3H]poly(C) probe in 3 M GuSCN for 10 min
      at 37 degrees C. Ribonuclease-resistant hybrids were collected by precipitation
      with trichloroacetic acid and filtration. Validation studies demonstrated minor
      interassay variance; the assay was accurate in the range 0.1 to 10 ng
      poly(I):poly(C12U). Thirty-one blood samples from 15 patients were collected and
      prepared before and immediately after an average 35 min intravenous infusion of
      40-500 mg poly(I):poly(C12U). Postadministration values averaged 48% (s.d. 23%)
      of the theoretical maximum (range 20-102%). These results confirm previous
      observations of rapid elimination kinetics of poly(I):poly(C12U) in patients.

PMID- 1974295
TI  - Inhibition of metoprolol metabolism by chloroquine and other antimalarial drugs.
AB  - The ability of a series of antimalarial drugs to impair the metabolism of
      metoprolol in rat and man has been examined. Chloroquine was a potent inhibitor
      in rat liver microsomes (Ki value for metoprolol alpha-hydroxylation = 0.18
      microM and for O-demethylation = 0.36 microM). The other antimalarial drugs also
      inhibited metoprolol oxidation. Quinine was similar to chloroquine in potency,
      while quinidine, primaquine and mefloquine were slightly less potent. Chloroquine
      also inhibited metoprolol oxidation in human liver microsomes, although it was
      about two orders of magnitude less potent than in the rat and the extent of
      impairment varied greatly between individual livers. Intraperitoneal
      administration of chloroquine to anaesthetized rats decreased the clearance of
      metoprolol (40 mg tartrate salt kg-1 i.p.) to 54, 34, 20 and 26% of the control
      value at doses of 2.5, 4.0, 25 and 40 mg kg-1, respectively. We conclude that
      antimalarial treatment might have contributed to a previously reported difference
      in the metabolic pattern of metoprolol between Caucasians and Nigerians.

PMID- 1974296
TI  - The effect of moisture content on the compression properties of maltodextrins.
AB  - The effect of moisture content on the compression properties of maltodextrin
      powders obtained by different degrees of hydrolysis (depolymerization) of corn
      starch has been studied using the yield pressure determined from the Heckel plot
      and the compact tensile strength measured by the diametrical compression method.
      An increase in the moisture content of the powder reduced the yield pressure and
      improved the densification for all five maltodextrins evaluated. At the same
      moisture level, the extent of densification which occurred during compaction was
      greater for maltodextrins with a lower degree of polymerization. Compacts
      produced by maltodextrins with a lower degree of polymerization also exhibited a
      greater tensile strength for a given pressure at a moisture content below 8.0%.
      However, further increase in moisture content resulted in a decrease in compact
      tensile strength for maltodextrins having a lower degree of polymerization.
      Despite the significant difference in compression behaviour, the five
      maltodextrins did not show noticeable differences in crystallinity as revealed by
      their x-ray powder diffraction pattern.

PMID- 1974297
TI  - Lipid peroxidation effects of a novel iron compound, ferric maltol. A comparison
      with ferrous sulphate.
AB  - Lipid peroxidation effects of ferric maltol have been compared with those of
      ferrous sulphate both in lecithin liposomes and in brush border and mitochondrial
      membranes prepared from rat small intestine. Ferrous sulphate, but not ferric
      maltol, initiated peroxidation in liposomes as measured by conjugated diene
      production, but, with 500 microM ascorbic acid present, both caused intense
      peroxidation which was inhibitable by N2, tocopherol, maltol and ferrous
      chelators, but not by OH or H2O2 scavengers. The rate of peroxidation increased
      with ferrous sulphate concentration up to 100 microM but was independent of
      ferric maltol concentration between 5-500 microM. Material eluted from rat small
      intestine contained a reducing factor, similar in size to ascorbic acid, capable
      of generating ferrous ions from ferric maltol and initiating peroxidation.
      Peroxidation in mitochondrial membranes appeared unaffected by addition of iron
      whilst that in brush border membranes was detectable only in the presence of
      iron. At iron concentrations of 100 microM and above ferric maltol produced less
      liposomal peroxidation than ferrous sulphate. Maltol itself may delay recycling
      of Fe3+ to Fe2+. Thus ferric maltol could provide a less toxic alternative to
      ferrous salts in the oral treatment of iron-deficiency.

PMID- 1974298
TI  - The importance of reductive mechanisms for intestinal uptake of iron from ferric
      maltol and ferric nitrilotriacetic acid (NTA).
AB  - Intestinal iron absorption is thought to proceed with iron mainly in the ferrous
      form, yet the novel iron complex, ferric maltol is an effective oral preparation.
      Although possessing a high oil: water partition coefficient, ferric maltol does
      not diffuse across the intestine but donates its iron to the endogenous uptake
      system. Reduction of the ferric iron in the gut lumen appears to precede iron
      uptake both from ferric maltol and from ferric nitrilotriacetic acid (NTA) which
      is a non-penetrating iron ligand. Uptake of radiolabelled iron (59Fe) into
      isolated fragments of rat small intestine was inhibited by the ferrous chelator,
      bathophenanthroline sulphonate (BPS) and enhanced at low concentrations by the
      reducing agent ascorbic acid. Spectrophotometric evidence was obtained that
      ferrous ions are generated from these ferric complexes in the presence of
      ascorbic acid and other reducing agents. The rate of ferrous ion formation was
      independent of ferric maltol concentration at low ascorbic acid levels and
      decreased with increasing ferric maltol concentration at higher levels of
      ascorbate. Maltol has a high affinity for ferric ions and may delay reduction at
      higher concentrations. By contrast, a higher rate of ferrous ion generation was
      seen with ferric NTA and this increased with iron ligand concentration. Washings
      from the intestinal lumen also brought about ferrous ion formation from these
      ferric ligands. Gel filtration revealed these reducing factors to be of low
      molecular weight. The washings, however, interfered with 59Fe uptake into the
      isolated fragments, but when reducing fractions only from the filtered washings
      were used, enhanced iron uptake was seen.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1974299
TI  - Species-dependent differences in the properties of particulate cyclic nucleotide
      phosphodiesterase from rat and rabbit ventricular myocardium.
AB  - The ability of cyclic nucleotide phosphodiesterases (PDEs) to hydrolyse cyclic
      (c)AMP in rat and rabbit ventricular myocardium has been compared. The PDE
      activity of rabbit, but not rat, cardiac homogenate and supernatant fraction was
      potentiated by Ca2+/calmodulin and attenuated by cGMP. Both rabbit and rat
      ventricular myocardium were shown to have a membrane bound PDE. However, rabbit
      membrane-bound PDE was inhibited by cGMP and low concentrations of milrinone
      (IC50 2.7 microM). In contrast, rat membrane-bound PDE was not inhibited by
      either cGMP or low concentrations of milrinone (IC50 19 microM), but it was
      potently inhibited by rolipram (IC50 2.2 microM). Thus, in rabbit the particulate
      PDE is milrinone sensitive (PDE III) whilst in rat it is the rolipram sensitive
      (PDE IV) isoenzyme. There are clearly species differences in the intracellular
      localization and relative activities of PDE isoenzymes in cardiac tissue. This
      may explain the species differences already found in the activity of selective
      PDE isoenzyme inhibitors as inotropic agents.

PMID- 1974300
TI  - Increased dopamine turnover in the ventral striatum by 8-OH-DPAT administration
      in the rat.
AB  - The administration of the 5-HT1A agonist 8-OH-DPAT (0.8 mumols kg-1 s.c.-40 min)
      produced an increase in dopamine (DA) turnover, estimated by the quotient (DOPAC
      + HVA) DA-1, in the ventral striatum of the rat. No statistically significant
      effects were obtained in the dorsal striatum. The accumulation of 3-MT in
      pargyline-treated animals (375 mumols kg-1 s.c.-60 min) was not affected by 8-OH
      DPAT treatment (0.15-2.4 mumols kg-1 s.c.-30 min). These findings indicate that 8
      OH-DPAT has weak antagonist properties at striatal DA receptors in normal rats.
      Both the 5-HT1A agonist flesinoxan (0.06-17.8 mumos kg-1 s.c. -50 min) and the
      mixed 5-HT1 and 5-HT2 agonist 5-MeODMT (1.6-26.0 mumols kg-1 s.c.-50 min)
      produced a decrease in forebrain 5-HTP accumulation (striatum and neocortex),
      following decarboxylase inhibition by means of NSD-1015 in reserpine treated
      rats, indicating stimulation of central 5-HT receptors by these two compounds. At
      the same time, the DOPA accumulation by the ventral striatum was decreased by
      flesinoxan and increased by 5-MeODMT treatment. These observations show that,
      under these conditions, the decrease in DA synthesis is not directly coupled to
      the decreased 5-HT synthesis produced by flesinoxan, as previously demonstrated
      for 8-OH-DPAT. Taken together with previous observations, the present results
      suggest that 8-OH-DPAT, depending on the experimental conditions, is an agonist
      or antagonist at striatal DA receptors, in all probability due to partial DA
      receptor agonist properties of the compound.

PMID- 1974301
TI  - Smoking, eicosanoids and ulcerative colitis.
AB  - In this study, which is the first of its kind using normal tissue samples that
      are very difficult to obtain, we have investigated the hypothesis that smoking
      protects against ulcerative colitis by altering the colonic mucosal formation of
      prostaglandins and related substances. Colonic mucosa biopsied from healthy young
      men produced prostaglandin E, 6-keto-PGF1 alpha (formed from PGI2), leukotriene
      B4 and leukotriene C4/D4/E4 as determined by radioimmunoassay. With each
      substance, the median yield was lower in the group of smokers who smoked 3
      cigarettes in the 2 h before biopsy, than in the non-smokers. However, with each
      eicosanoid the statistical probability approached only the 10% level, but the
      fact that the trend was the same for all eicosanoids somewhat strengthens the
      possibility of a real difference between the groups.

PMID- 1974302
TI  - Antidiabetic and aldose reductase activities of biflavanones of Garcinia kola.
AB  - Kolaviron, a mixture of C-3/C-8 linked biflavonoids obtained from Garcinia kola
      produces significant hypoglycaemic effects when administered intraperitoneally to
      normal and alloxan diabetic rabbits at a dose of 100 mg kg-1. The fasting blood
      sugar in normoglycaemic rabbits was reduced from 115 mg/100 mL to 65 mg/100 mL
      after 4 h. In alloxan diabetic rabbits, the blood sugar was lowered from 506
      mg/100 mL to 285 mg/100 mL at 12 h. The hypoglycaemic effects have been compared
      with those of tolbutamide. Kolaviron inhibited rat lens aldose reductase (RLAR)
      activity, with an IC50 value of 5.4 x 10(-6). The significance of these findings
      in the potential use of kolaviron as an antidiabetic agent is discussed.

PMID- 1974303
TI  - Insulin absorption from conjunctiva studied in normal and diabetic dogs.
AB  - The dynamics of insulin absorption from the ocular conjunctiva of anaesthetized
      normal and pancreatectomized dogs have been examined. A porcine insulin
      preparation of 1000 units mL-1 (pH 8.0) was administered as either 1 or 10 units
      kg-1 to the upper conjunctival sacs of recumbent dogs following an overnight
      fast. Plasma insulin concentrations increased significantly at 5 min after the
      insulin administration. Plasma glucose concentrations decreased significantly, in
      both normal (given 10 units kg-1) and diabetic dogs (given 1 unit kg-1 or 10
      units kg-1). There was a dose-dependent increase in plasma insulin concentration
      following conjunctival administration. Estimated absorption was significantly
      higher in diabetic than in normal dogs.

PMID- 1974304
TI  - Antihistaminic activity of pulegone on the guinea-pig ileum.
AB  - Pulegone, a natural monoterpene compound, has an antihistamine effect on guinea
      pig ileum. Its antagonism is of the competitive type (PA2 = 6.35) like that of
      mepyramine and dexchlorpheniramine, two H1-antagonists, with PA2 values of 10.15
      and 8.74, respectively.

PMID- 1974305
TI  - Receptor-mediated prednisolone pharmacodynamics in rats: model verification using
      a dose-sparing regimen.
AB  - Our receptor/gene-mediated model of corticosteroid action was tested and extended
      by examining the pharmacokinetics/dynamics of multiple low doses vs. a single
      higher dose of intravenously administered prednisolone in adrenalectomized male
      Wistar rats. Low-dose rats received 3 bolus doses (5 mg/kg) of prednisolone at 0,
      0.5 and 1.0 hr. High-dose animals were given a single 25 mg/kg dose of
      prednisolone. Both regimens were expected to produce equivalent net responses
      based on model predictions. Control rats were not dosed. The profiles of free
      hepatic cytosolic glucocorticoid receptors and the hepatic tyrosine
      aminotransferase (TAT) enzyme were examined. Plasma prednisolone concentrations
      showed bi-exponential decline for both doses using pooled animal data. Clearance
      of total plasma prednisolone was 4.16 and 3.21 L/hr per kg in low- and high-dose
      groups. Volume of distribution at steady state (approximately 1.50 L/kg) and
      central volume (approximately 0.6 L/kg) were similar for both groups. Receptor
      levels from 5-16 hr stabilized at 64% of the 0-hr control value. Receptor and TAT
      profiles were essentially superimposable for both dosing groups. Our previous
      model was used to simultaneously describe prednisolone plasma concentrations,
      hepatic receptors, and TAT activity. The ability of total plasma prednisolone
      (Cp), corticosteroid binding globulin (CBG)-free plasma prednisolone (CCBG), and
      free plasma prednisolone (CF) to describe the kinetics/dynamics were examined.
      The CF values produced optimum fitting of all receptor data. The similarity of
      the two dosing groups supports the view that appropriately timed doses of a
      steroid can be used in an optimally efficacious manner by first filling all
      receptor sites and then replacing steroid as receptors are expected to recycle
      from nuclear/DNA binding sites as the steroid is eliminated.

PMID- 1974306
TI  - Prescription of benzodiazepines in a London teaching hospital.
AB  - A study of the extent of hospital inpatient prescribing of benzodiazepines and
      their continuation at discharge was carried out on all patients admitted to St
      Bartholomew's Hospital, London, during a 7-day period. A large majority (73.6%)
      were not prescribed benzodiazepines at any time. No discharge prescriptions for
      these drugs were initiated in hospital. The data do not suggest that hospital
      prescribing of benzodiazepines is contributing to community prescribing.

PMID- 1974307
TI  - Prospects for new drug treatment in epilepsy: a review.

PMID- 1974308
TI  - Identification and characterization of a testis-specific isoform of a chaperonin
      in a moth, Heliothis virescens.
AB  - Two relatively abundant proteins having subunit molecular weights of 60,000 and
      63,000 (p60 and p63, respectively) have been purified as a 16 to 18S complex from
      sperm mitochondria of a moth. Heliothis virescens. Although the function of these
      proteins had heretofore not been established, interest in the p63 polypeptide
      stemmed from its sperm-specific expression and its striking occurrence as a net
      charge variant among several insect species surveyed, using two-dimensional gel
      electrophoresis. Genomic and cDNA clones corresponding to the p63 protein have
      now been isolated and their sequencing has revealed extensive amino acid sequence
      identity with both the Escherichia coli GroEL protein and its eukaryotic
      homologues, the chaperonins. Immunoblot studies with a Tetrahymena chaperonin
      antiserum demonstrated that the p60 protein, which is expressed in all cell
      types, is structurally related to p63 and is itself a chaperonin subunit. While
      the chaperonin complex from Heliothis sperm shares certain properties with GroEL,
      including the ability to hydrolyze ATP and organization of its subunits into a
      seven-member ring, electron microscopic analysis revealed that its higher-order
      structure differed from GroEL (and other lower eukaryotic chaperonins) in that
      the native particle comprises one such ring rather than a doublet. It is not yet
      known whether the two chaperonin isoforms coexpressed in moth sperm assemble
      separately or give rise to hybrid particles. In either case, the existence of
      multiple chaperonin subunits in sperm leaves open the possibility that some
      aspect of mitochondrial biogenesis that is dependent upon the activity of these
      proteins is qualitatively or quantitatively different in this cell type.

PMID- 1974309
TI  - Head injury: an immunologic deficit in T-cell activation.
AB  - Despite progress in the management of increased pressure following head injury,
      infection remains the most common complication in survivors. This study attempted
      to better define the immunologic deficit that occurs immediately and in the early
      post-recovery period following severe head injury. Twenty-seven patients admitted
      with the primary diagnosis of severe head injury (mean Glasgow Coma Score, 6.75)
      were studied within 24 hours of injury and at weekly intervals. T-cell
      proliferative response to mitogen stimulation was assessed. T-cell antigen
      expression following PHA stimulation was assessed for helper (CD4) and suppressor
      (CD8) subpopulations: the early T-cell activation antigens interleukin-2 receptor
      (IL2R) and transferrin receptor (TFR), and the late antigen (HLA-DR) using flow
      cytometry. Polymorphonuclear leukocyte function was assessed using oxidative
      burst. There was a reduction in the proliferative response of T cells to mitogen
      stimulation. The B-cell response seemed unaffected. The diminished proliferative
      response was accompanied by diminished expression of early activation antigens
      (IL2R and TFR) and late (following DNA synthesis) (HLA-DR). This was seen
      primarily on helper/inducer cells (CD4+). Polymorphonuclear leukocyte function
      was unaffected.

PMID- 1974311
TI  - The effect of plasma valine, isoleucine and leucine on the control of the flux
      through tyrosine- and tryptophan-hydroxylase in the brain.
AB  - The effect of increasing blood levels of valine, isoleucine and leucine on the
      fluxes through tyrosine and tryptophan hydroxylase in brain has been calculated
      and analysed in terms of flux control coefficients. It is concluded that any
      beneficial effect of increasing the concentration of these amino acids in
      phenylketonuria patients is not due to a decrease in brain phenylalanine or an
      improved neurotransmitter synthesis through tyrosine or tryptophan hydroxylase.

PMID- 1974310
TI  - The importance of multiple endocrine neoplasia syndromes in differential
      diagnosis.
AB  - In the differential diagnosis of endocrine symptoms, the autosomal dominant
      multiple endocrine neoplasia (MEN) syndromes are rare but important. We found
      seven index cases of MEN-I in 176 patients with adenomas of the anterior
      pituitary and 26 patients with primary hyperparathyroidism. Of 23 cases of
      medullary thyroid carcinoma and eight cases of pheochromocytoma, 14 patients are
      classified as MEN-IIa and one as MEN-IIb. Family screening identified six MEN-I
      and seven MEN-II cases among 32 individuals examined. Because of autosomal
      dominant inheritance and sometimes-delayed manifestation of the complete
      syndrome, screening of healthy and affected family members should be repeated at
      least every other year.

PMID- 1974312
TI  - 19th annual UCLA symposium: Molecular biology of neurotransmitters and their
      receptors. Abstracts.

PMID- 1974313
TI  - [Significance of flumazenil in acute benzodiazepine poisoning].
AB  - Thirty-five patients over 14 years of age were evaluated, with the common feature
      of benzodiazepine poisoning, either as a single drug or associated with others
      and/or with ethanol, and who had a Glasgow score lower than 10 at admission.
      These patients were treated with flumazenil as a competitive antagonist drug. The
      results were very satisfactory. Subsequently, the possible relationship between
      the effect of flumazenil and the pharmacokinetic benzodiazepine profile was
      evaluated, and a significant relationship between the half life and the degree of
      resedation of the patients was found.

PMID- 1974314
TI  - [Usefulness of positron-emission tomography in the study of the central nervous
      system].

PMID- 1974315
TI  - Interaction of cyclic AMP and cell-cell contact in the control of tyrosine
      hydroxylase RNA.
AB  - The interaction between cell-cell contact and cyclic AMP-mediated control of the
      rat tyrosine hydroxylase (TH) gene was investigated in subclones of the PC12 rat
      pheochromocytoma cell line. Increasing cell culture density and elevation of
      intracellular cyclic AMP levels with forskolin both cause augmentation of TH RNA
      levels. However, the extent of increase in TH RNA following forskolin treatment
      is less in cultures grown at high density than those at low density, suggesting
      that there may be an interaction in the mechanism by which these two treatments
      modulate TH RNA levels. The role of cis-acting sequences in the TH gene in the
      induction of TH RNA by cyclic AMP and cell density was determined by the use of
      plasmid constructs containing the 5'-flanking sequences of the TH gene directing
      the transcription of the reporter gene, chloramphenicol acetyltransferase (CAT).
      Using transient transfection assays in PC12 cells, we have mapped the site of
      cyclic AMP regulation of the TH gene to a region between -60 and -41. Stable
      transformants of PC12 cells which express p5'TH CAT (-773/+27) were isolated and
      the activity of CAT following treatment of cells with forskolin and growth at
      different cell densities was evaluated. CAT activity does not differ between
      cells grown at low or high density. Forskolin induces CAT activity 2-4 fold, but
      the extent of induction does not vary with changes in cell culture density. We
      conclude from these experiments that the intracellular mechanism by which
      increased cell-cell contact modulates TH RNA levels is not through interaction
      with the same genomic elements as those which regulate gene expression by cyclic
      AMP.

PMID- 1974316
TI  - Tyrosine hydroxylase messenger RNA in the hypothalamus, substantia nigra and
      adrenal medulla of old female rats.
AB  - The effects of aging in the female rat were analyzed in terms of tyrosine
      hydroxylase (TH) gene expression and serum prolactin levels. The number of
      tuberoinfundibular dopaminergic (TIDA) neurons and the concentration of TH mRNA
      per cell was greater in 16- to 18-month-old rats than in 25-month-old rats. The
      amount of TH immunostaining was more intense in the median eminence of the 18
      month-old rats compared to either younger or older rats. Plasma prolactin levels
      were moderately elevated in 18-month-old rats compared to 4-month-old rats, and
      extremely elevated in 25-month-old rats due to the occurrence of pituitary
      prolactinomas. There were no detectable changes in TH mRNA levels in the
      substantia nigra with age, whereas adrenal TH mRNA increased with age. We propose
      that prolactin initially exerts a stimulatory effect on the TIDA neurons as the
      rat ages, but eventually causes a loss in neuronal number and neuronal function
      as the pituitary prolactinoma secretes increased amounts of prolactin.

PMID- 1974317
TI  - [The central nervous system and inflammation: the role of opioid peptides].
AB  - Inhibition of human granulocyte aggregation was observed in the presence of
      morphine in a naloxone stereoselective way, while the opioid peptides were
      ineffective. In comparative studies Ca(+)+ (A23187) and dynorphin 1-9, per se,
      induced stimulation of arachidonic acid metabolites from granulocytes. In this
      regard dynorphin 1-9 may function as a mediator between the central nervous
      system and the inflammation.

PMID- 1974318
TI  - [The effects of nizatidine and misoprostol on peptic activity and gastric mucus].
AB  - The effects of Nizatidine, an H2-receptor antagonist, and Misoprostol, a PGE1
      analogue, on gastric pH, pepsin, pepsinogen group I and N-acetylneuraminic acid
      concentration were evaluated in a group of 20 patients with duodenal ulcer.
      Nizatidine decreased pepsin concentration while it increased gastric pH, although
      not to a significant degree and left pepsinogen group I and N-acetylneuraminic
      acid concentration unchanged. Misoprostol did not modify gastric pH, pepsin and N
      acetylneuraminic acid values but it increased pepsinogen group I levels. These
      data support the view that H2-receptor antagonists, especially Nizatidine, and
      Misoprostol do not directly affect pepsin and/or N-acetylneuraminic acid
      concentration.

PMID- 1974319
TI  - Glucocorticoid-mediated induction of glutamine synthetase in skeletal muscle.
AB  - We studied the effect of glucocorticoids on glutamine synthetase in rat skeletal
      muscle in culture and in vivo. Dexamethasone, a synthetic glucocorticoid, caused
      striking, receptor-mediated increases in both glutamine synthetase activity and
      the steady-state glutamine synthetase mRNA level. This effect was observed in rat
      skeletal muscle cells in culture, as well as in rat muscles in vivo.
      Glucocorticoid-mediated induction of glutamine synthetase was blocked by
      androgenic/anabolic steroids at high doses, suggesting that anabolic steroids
      might have an anticatabolic mode of action in enhancing skeletal muscle mass in
      athletes. Further studies of the control of glutamine synthetase expression may
      shed light on mechanisms of muscle atrophy and hypertrophy.

PMID- 1974320
TI  - Deletions of chromosomal regions coding for fimbriae and hemolysins occur in
      vitro and in vivo in various extraintestinal Escherichia coli isolates.
AB  - Fimbrial adhesins and hemolysins contribute to pathogenicity of extraintestinal
      Escherichia coli isolates causing urinary tract infections (UTI), sepsis and new
      born meningitis (NBM). Using gene cloning techniques and pulse field
      electrophoresis in combination with Southern hybridizations it was demonstrated
      that the genetic determinants coding for P and 'P-related' fimbrial adhesins and
      hemolysins are closely linked on the chromosomes of different pathogenic E. coli
      wild-type isolates. For two UTI strains, 536 (O6:K15) and J96 (O4:K6), a co
      deletion of the linked gene clusters coding for hemolysin and fimbriae was
      observed. The deleted DNA regions which also comprise flanking DNA sequences were
      termed 'pathogenicity DNA islands'. Such 'pathogenicity DNA islands' were also
      detected in the genome of O18:K1 isolates of OMP type 6 but were absent on the
      chromosomes of O18:K1 strains of OMP type 9. A mutant strain, 536-22 was selected
      from rat kidneys after intraurethral infection of animals with the wild-type
      parental strain 536. This particular isolate also shows deletions of
      'pathogenicity islands' leading to a non-pathogenic phenotype. It is therefore
      concluded that excisions of 'pathogenicity islands' from chromosomes of
      pathogenic E. coli strains are not restricted to the laboratory but also occur in
      vivo. The generation of deletions may represent a general mechanism of bacterial
      virulence modulation.

PMID- 1974321
TI  - Messenger RNA turnover in cell-free extracts.

PMID- 1974322
TI  - Preparation of mammalian extracts active in polyadenylation.

PMID- 1974323
TI  - Selection and coamplification of heterologous genes in mammalian cells.

PMID- 1974324
TI  - Direct control of antennal identity by the spineless-aristapedia gene of
      Drosophila.
AB  - Loss-of-function mutations in the spineless-aristapedia gene of Drosophila (ssa
      mutants) cause transformations of the distal antenna to distal second leg,
      deletions or fusions of the tarsi from all three legs, a general reduction in
      bristle size, and sterility. Because ssa mutants are pleiotropic, it has been
      suggested that ss+ has some rather general function and that the ssa antennal
      transformation is an indirect consequence of perturbations in the expression of
      other genes that more directly control antennal or second leg identity. Here we
      test whether the ssa transformation results from aberrant expression of
      Antennapedia (Antp), a homeotic gene thought to specify directly the identity of
      the second thoracic segment. We find that Antp-ssa mitotic recombination clones
      in the distal antenna behave identically to Antp+ ssa clones, and are transformed
      to second leg. This demonstrates that the ssa antennal transformation is
      independent of Antp+, and suggests that ss+ may itself directly define distal
      antennal identity. The results also reveal that Antp+ is not required for the
      development of distal second leg structures, as these develop apparently normally
      in Antp- ssa antennal clones. Because Antp- mutations cause deletions or
      transformations that are restricted to proximal structures, whereas ssa alleles
      cause similar defects that are distally restricted, we suggest that ss+ and Antp+
      may play similar, but complementary, roles in the distal and proximal portions of
      appendages, respectively.

PMID- 1974325
TI  - Increase in hepatic microsomal lipid peroxidation mediated by alpha-adrenergic
      system under cold stress and noradrenaline treatment.
AB  - Lipid peroxidation measured both by the formation of malondialdehyde and by
      oxygen uptake in presence of NADPH, Fe2+ and ADP in hepatic microsomes increased
      on cold exposure and decreased on heat exposure of rats. Malondialdehyde content
      of isolated microsomes also showed similar changes. Treatment of animals with
      noradrenaline or a alpha-adrenergic agonist, phenylephrine, increased lipid
      peroxidation which was prevented by simultaneous treatment with cycloheximide, a
      protein synthesis inhibitor. Cold- and noradrenaline-induced increases were not
      found in animals pretreated with alpha-adrenergic receptor antagonist,
      phenoxybenzamine, but not with propranolol, a beta-adrenergic blocking agent. The
      concentration of the microsomal cytochromes P-450 and b5 remained unaffected
      under these conditions but the activity of NADPH-cytochrome c reductase showed
      parallel changes. These observations suggest a role for lipid peroxidation in
      cellular thermogenesis in liver tissue.

PMID- 1974326
TI  - Somatostatin gene expression in hypothalamus and cortex of aging male rats.
AB  - Somatostatin has been reported to decrease with age in many brain regions and
      these changes generally have been considered to have important implications for
      the regulation of both neural activity and neuroendocrine regulatory systems. The
      purpose of this study was to determine whether the age-related changes in
      somatostatin concentration in cortex and hypothalamus are attributable to
      alterations in the regulation of somatostatin gene expression. Hypothalamic and
      cortical tissue were dissected from young (3-4 month), middle-aged (12-14 month),
      and old (22 month) male Fischer 344 rats. Total RNA was extracted and dilutions
      blotted to nitrocellulose. Somatostatin cDNA in expression vector pSP65 was used
      to produce a 32P-labeled antisense probe for hybridization. After washing, blots
      were autoradiographed and analyzed by densitometry. Dilutions of total RNA were
      also probed with 32P-labeled oligo d(pT)16 to determine poly A +RNA levels. Data
      were expressed as relative somatostatin gene expression (somatostatin mRNA/poly A
      +RNA). Results indicated that in cortex, relative somatostatin gene expression
      was similar in young, middle-aged, and old animals (0.54 +/- 0.11, 0.60 +/- 0.08,
      and 0.51 +/- 0.04, respectively). However, somatostatin gene expression in the
      hypothalamus decreased consistently with age and ratios in old rats were
      approximately 50% of levels observed in young animals (p less than 0.05).
      Northern analysis of RNA revealed a single somatostatin transcript of
      approximately 0.65 kb in all age groups. In situ hybridization analysis of
      somatostatin mRNA in the hypothalamus indicated that the age-related decrease in
      somatostatin gene expression is a consequence of decreased expression within
      specific hypothalamic nuclei rather than a loss of somatostatin-containing
      neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1974327
TI  - Heterosynaptic correlates of long-term potentiation induction in hippocampal CA3
      neurons.
AB  - Previous studies have demonstrated that tetanization of hippocampal mossy fibers
      induces a long-term potentiation of non-tetanized (heterosynaptic) non-mossy
      fiber afferents (Schaffer collateral/commissural and fimbrial fibers).
      Tetanization of these non-mossy fiber afferents, in contrast, does not induce
      mossy fiber long-term potentiation, but induces a long-term depression of mossy
      fiber responses (Bradler and Barrionuevo, Synapse 4, 132-142, 1989). The synaptic
      activity necessary to evoke these heterosynaptic alterations of efficacy is not
      known. Specifically, the dependence of heterosynaptic efficacy on the activation
      of N-methyl-D-aspartate receptors has not been assessed. In addition, the
      capability of different afferents to CA3 neurons to support alterations in
      heterosynaptic efficacy remains largely unknown. In the present study,
      heterosynaptic alterations of efficacy in the rat did not require the activation
      of N-methyl-D-aspartate receptors. Mossy fibers supported N-methyl-D-aspartate
      receptor-independent heterosynaptic long-term depression, and N-methyl-D
      aspartate receptor-independent long-term potentiation. In contrast, non-mossy
      fiber afferents expressed N-methyl-D-aspartate receptor-independent
      heterosynaptic long-term potentiation induced by a mossy fiber tetanus, and an N
      methyl-D-aspartate receptor-independent long-term depression, in addition to N
      methyl-D-aspartate receptor-dependent homosynaptic long-term potentiation. The
      possibility that non-N-methyl-D-aspartate receptor activity in non-tetanized
      afferents is necessary for heterosynaptic long-term potentiation induction is
      discussed. Heterosynaptic long-term depression was induced in the absence of
      homosynaptic long-term potentiation, suggesting that these concomitant forms of
      synaptic plasticity rely on different mechanisms.

PMID- 1974328
TI  - In vivo release of endogenous glutamate and aspartate in the rat striatum during
      stimulation of the cortex.
AB  - The release of endogenous glutamate and aspartate from corticostriate neurons in
      the anaesthetized rat was investigated. Efflux of glutamate, aspartate and
      leucine in push-pull cannula perfusates of the striatum was measured in 1 min
      fractions collected before, during and after a 4 min stimulation period of
      ipsilateral frontal cortex. Efflux of the putative excitatory amino acid
      transmitters, glutamate and aspartate, determined during the first minute of
      stimulation, was significantly elevated above prestimulation resting level (by
      167% and 316%, respectively), while efflux of leucine, a non-transmitter amino
      acid, remained unchanged. Efflux of glutamate and aspartate during the last 3 min
      of stimulation dropped rapidly, indicating the activation of a regulatory
      mechanism, presumably re-uptake. The data further support the hypothesis that
      glutamate and/or aspartate act as transmitters or are metabolites of transmitters
      in the corticostriate pathway.

PMID- 1974329
TI  - Neurotransmitter release and synaptic vesicle recycling.

PMID- 1974330
TI  - Effects of ethanol and Ro 15-4513 in an electrophysiological model of anxiolytic
      action.
AB  - Previous research has implicated hippocampal rhythmical slow activity in the
      mechanisms of action of the anxiolytic drugs. In this study ethanol and a
      putative ethanol antagonist, Ro 15-4513, were investigated with reticular
      elicitation of rhythmical slow activity. Doses of ethanol between 0.6 and 3.1
      g/kg were used. Ethanol reduced the frequency of reticular-elicited rhythmical
      slow activity in the same way as has been reported for anxiolytic barbiturates
      and benzodiazepines. This effect was linearly related to log dose of ethanol in
      the range of 1.7-3.1 g/kg. Ro 15-4513 at a dose of 2 mg/kg reduced the effect of
      ethanol (2.0 g/kg) but had no action itself. Ethanol also decreased the slope of
      the stimulation voltage-rhythmical slow activity frequency function but this
      effect was not reduced by Ro 15-4513. These results show that ethanol acts in a
      similar manner to conventional anxiolytic drugs but that only one component of
      this action can be reduced by Ro 15-4513.

PMID- 1974331
TI  - Inhibition of potassium currents by the sigma receptor ligand (+)-3-(3
      hydroxyphenyl)-N-(1-propyl)piperidine in sympathetic neurons of the mouse
      isolated hypogastric ganglion.
AB  - The actions of (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine [(+)3-PPP] on
      sympathetic neurons of the mouse isolated hypogastric ganglion were studied using
      the current clamp and single electrode voltage clamp techniques. In neurons
      studied under current clamp (+)3-PPP (10(-5) to 3 x 10(-4) M) evoked a
      concentration-dependent depolarization, which was fully reversible on washout of
      the drug. The depolarization was associated with an increase in membrane input
      resistance. At membrane potentials between -43 and -65 mV the amplitude of the
      depolarization was inversely related to the membrane potential. (+)3-PPP had no
      effect on membrane potential at potentials negative to -65 mV. The effect of (+)3
      PPP on the M-current was studied in cells voltage clamped at -40 mV and stepped
      to -60 mV for 300-500 ms. The slow current relaxations seen during and after the
      voltage step are largely due to the M-current. (+)3-PPP (3 x 10(-5) to 3 x 10(-4)
      M) inhibited the M-current and produced an inward current in a concentration
      dependent manner. (-)3-PPP (3 x 10(-5) M) had similar effects, but was less
      potent than (+)3-PPP. (+)3-PPP (3 x 10(-5) M) also inhibited the A-current and a
      calcium-dependent potassium current, but to a lesser degree than the M
      current.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1974332
TI  - Cortical neurons containing somatostatin- or parvalbumin-like immunoreactivity
      are atypically vulnerable to excitotoxic injury in vitro.
AB  - We exposed murine cortical neuronal cell cultures for 24 hours to defined
      concentrations of N-methyl-D-aspartate (NMDA), kainate, or alpha-amino-3-hydroxy
      5-methyl-4-isoxazolepropionic acid (AMPA), and assessed the resultant neuronal
      degeneration quantitatively by the efflux of lactate dehydrogenase to the bathing
      medium. The small subpopulations of neurons that stained immunohistochemically
      for either somatostatin- or parvalbumin-like reactivity were atypically affected
      by these excitotoxins. Limited exposure to kainate or AMPA did little damage to
      the general neuronal population, but destroyed nearly all somatostatin- or
      parvalbumin-reactive cells. Conversely, these immunoreactive cells were more
      resistant to NMDA-induced injury than the general population. In view of reports
      suggesting that somatostatin- and parvalbumin-reactive cortical neurons may be
      preferentially damaged in Alzheimer's disease, these observations support a
      hypothesis that the overactivation of non-NMDA receptors could be involved in
      Alzheimer's disease pathogenesis.

PMID- 1974333
TI  - Pre-inspiratory burst in the caudal medulla of rabbits.
AB  - The activity of 48 respiratory units in the paraolivary region from the middle to
      the rostral end of the hypoglossal cranial nerve root, and the effect of
      electrical stimulation and L-glutamate applied to the region on phrenic nerve
      activity was investigated in 14 rabbits. Electrical stimulation (50 Hz, 0.2 ms
      current pulses at intensities 5-20 microA) and L-glutamate (30-100 ng) shortened
      the expiratory time and increased the respiratory rhythm with no change in tidal
      phrenic nerve activity. Rhythmic activity preceding the phrenic nerve activity
      (pre-inspiratory burst) was recorded in the paraolivary region. The temporal
      relationship between the pre-inspiratory (pre-I) burst and the phrenic activity
      remained constant even when the respiratory frequency was altered by passive lung
      inflation. These results suggest that structures in the paraolivary region may
      influence the respiratory rhythm in rabbits and that pre-I burst neurons may play
      a role in triggering periodic phrenic activity.

PMID- 1974334
TI  - Is GABA release modulated by presynaptic excitatory amino acid receptors?
AB  - The purely GABAergic nature of spontaneous synaptic activity in cultures from the
      neonatal rat superior colliculus (SC) is of great advantage in investigations
      aimed at characterizing presynaptic factors regulating GABAergic synaptic
      transmission. Using SC-derived cultures it was confirmed that excitatory amino
      acids (EAA) can induce a marked increase in the frequency of spontaneous synaptic
      Cl- currents (ICl(GABA)SYN). However, this tetrodotoxin-resistant facilitation of
      Ca2(+)-dependent GABA release required application of EEA to several neurons
      (multiple cell superfusion). In contrast, no frequency increase of Icl(GABA)SYN
      was seen with restricted access of EAA to only one neuron and the presynaptic
      axonal terminals (single cell superfusion). It is therefore concluded that the
      strong facilitatory effect of glutamate (Glu) and kainate (KA) on GABAergic
      synaptic activity, as observed under the condition of multiple cell superfusion,
      is mediated via somatodendritic excitatory amino acid receptors (EAARs).

PMID- 1974335
TI  - Further characterisation of excitatory amino acid receptors coupled to
      phosphoinositide metabolism in astrocytes.
AB  - Excitatory amino acids stimulate phosphoinositide breakdown in astrocytes with
      the following rank order of effect: quisqualate greater than ibotenate =
      glutamate greater than kainate greater than N-methyl-D-aspartate. Quisqualate
      induced responses were resistant to blockade with a range of receptor antagonists
      whereas those to glutamate were partially reversed by gamma-D
      glutamylaminosulphonic acid and gamma-D-glutamylglycine. These antagonists were,
      however, more effective against kainate-stimulated phosphoinositide metabolism.
      These experiments together with those where combinations of agonists were used,
      suggest that the kainate-induced and, to some extent, the glutamate-induced
      responses were due to membrane depolarisation and that quisqualate activates a
      non-ionotropic class of receptor at which glutamate and ibotenate are partial
      agonists.

PMID- 1974336
TI  - NMDA antagonists interact with 5-HT-stimulated phosphatidylinositol metabolism
      and impair passive avoidance retention in the rat.
AB  - The NMDA receptor antagonists APV (5 micrograms/10 microliters/rat i.c.v.) or
      ketamine (12.5 mg/kg i.p.), administered 5 min before training, decreased the
      retention of a passive avoidance conditioning. In hippocampal or cortical slices
      of APV- and ketamine-treated rats, 5-HT-stimulated phosphoinositide metabolism
      was potentiated. It is suggested that excitatory amino acids could modulate the
      mechanism operative in signal transduction of serotonin; this interaction could
      play a role in memory retention.

PMID- 1974337
TI  - Differential effects of NMDA receptor antagonist APV on tetanic stimulation
      induced and calcium induced potentiation.
AB  - Enduring synaptic potentiation can be induced in area CA1 of hippocampus by
      tetanic stimulation and by exposure to a medium containing high Ca2+
      concentration. Both tetanic stimulation and high Ca2+ induce potentiation through
      voltage-dependent, post-synaptic mechanisms. Tetanus-induced long-term
      potentiation (LTP) was blocked by 50 microM D,L-2-amino-5-phosphonovalerate (APV)
      as previously reported by others. In contrast, Ca2(+)-induced long-lasting
      potentiation was not reduced by 50 microM APV. Thus the mechanisms by which
      tetanic stimulation and exposure to high Ca2+ induce synaptic potentiation may
      differ.

PMID- 1974338
TI  - Brain natriuretic peptide stimulates particulate guanylate cyclase activity in
      selected areas of the rat brain.
AB  - The effect of porcine brain natriuretic peptide (pBNP) on cyclic guanosine
      monophosphate (cGMP) production was investigated in localized rat brain areas by
      radioimmunoassay procedure. Porcine BNP activated particulate guanylate cyclase
      in the median eminence, subfornical organ, choroid plexus, olfactory bulb,
      paraventricular nucleus and pineal gland in a concentration-dependent fashion and
      its action was comparable to that of rat atrial natriuretic peptide (alpha-ANP),
      with ED50 values ranging from 5 to 7 x 10(-7) M for both peptides. Our results
      suggest that the activation of a specific receptor coupled to the guanylate
      cyclase system and the subsequent elevation of cGMP levels constitutes the common
      mechanism of the central action of BNP and ANP.

PMID- 1974339
TI  - [3H]Dihydrotetrabenazine, a new marker for the visualization of dopaminergic
      denervation in the rat striatum.
AB  - [3H]Dihydrotetrabenazine ([3H]TBZOH), a derivative of the monoamine depleting
      agent, tetrabenazine, has been shown to bind to the vesicular monoamine
      transporter. We studied the effect of unilateral nigral lesion with 6
      hydroxydopamine on [3H]TBZOH binding in the striatum by means of quantitative
      autoradiography. Topographical analysis of striatal [3H]TBZOH binding showed in
      control rats a pattern similar to the known distribution of dopaminergic
      innervation, and allowed to visualize dopaminergic denervation in lesioned rats.
      A good correlation was found between striatal [3H]TBZOH binding levels and
      tyrosine hydroxylase activities in similar areas on adjacent slices following 6
      OHDA lesions with varying severity. These data reveal that autoradiography of
      [3H]TBZOH binding is a good index for the visualization and quantitation of
      dopaminergic nerve terminals integrity in the striatum.

PMID- 1974340
TI  - Injection of a cholinergic agonist in the dorsolateral pontine tegmentum of cats
      affects the posturokinetic responses to cortical stimulation.
AB  - Microinjection into the dorsolateral pontine tegmentum of the muscarinic agonist
      bethanechol, leading to activation of cholinoceptive pontine reticular formation
      (pRF) neurons and the related medullary inhibitory reticulospinal system, did not
      modify the threshold, latency and amplitude of the forelimb flexion elicited by
      unilateral stimulation of the corresponding motor cortex. However, the remaining
      limbs which displayed a diagonal pattern of postural adjustments showed a
      dissociation of their postural responses in 2 components: the early component of
      central origin greatly decreased in amplitude, while the late component
      attributed to reflex mechanism triggered by the unbalance brought about by the
      flexion movement increased. Further evidence indicated that the pRF system
      intervenes in the gain regulation of the early postural responses during the
      cortically induced limb movement.

PMID- 1974341
TI  - Distribution of N-acetylaspartate, N-acetylaspartylglutamate, free glutamate and
      aspartate following complete mesencephalic transection in rat neuraxis.
AB  - The distribution of N-acetylaspartate (NAA), N-acetylaspartylglutamate (NAAG),
      free glutamate (Glu) and aspartate (Asp) was studied in the neuraxis of rats 48 h
      after complete transection of brain stem at the intercollicular level. NAA
      remained unchanged above the transection level but decreased in the neur-axis
      segments caudal to the lesion. Glu was strongly depressed both in the segments
      rostral to the transection and in the ones caudal to it. No significant change
      was found for NAAG and Asp. These findings are consistent with the hypothesis
      that NAA may be involved in neurotransmission processes and provide further
      evidence for Glu as transmitter of descending and ascending pathways. In
      addition, the data obtained do not suggest a direct metabolic or functional
      relationship between NAA and NAAG nor between these N-acetylderivatives and free
      Glu and Asp.

PMID- 1974342
TI  - Expression of epidermal growth factor receptor and HER-2/neu in normal and
      neoplastic cervix, vulva, and vagina.
AB  - Monoclonal antibodies were used to localize immunohistochemically epidermal
      growth factor receptor and HER-2/neu in normal and neoplastic frozen tissue
      samples from the lower genital tract of women. In squamous epithelia of the
      cervix, vulva, and vagina, epidermal growth factor receptor and HER-2/neu both
      were expressed most strongly by basal keratinocytes. Expression of both of these
      cell surface molecules decreased as cells underwent differentiation toward the
      mucosal surface. In contrast, both epidermal growth factor receptor and HER-2/neu
      were expressed throughout the entire thickness of the epithelium by
      undifferentiated squamous cells in squamous metaplasia, raised condyloma, and
      carcinoma in situ. In 34 squamous cancers of the cervix, vulva, and vagina, all
      malignant cells were found to have moderate to heavy staining for epidermal
      growth factor receptor. Staining of 33 of these cancers for HER-2/neu was light,
      although one patient who presented with distant metastases had heavy staining for
      HER-2/neu. These data suggest that although overexpression of HER-2/neu in
      squamous cancers of the lower genital tract is a rare event, it may be associated
      with aggressive biologic behavior.

PMID- 1974343
TI  - Nobel conference: a report.

PMID- 1974344
TI  - The natural course of HIV infections.

PMID- 1974345
TI  - [The reactivity of postsynaptic alpha 1- and alpha 2-adrenoreceptors and arterial
      pressure in acute pancreatitis].
AB  - Experiments were conducted on pithed rats with acute pancreatitis and on falsely
      operated on animals (ether-laparotomy stress) to study the reactivity of vascular
      alpha 1- and alpha 2-adrenoreceptors and its role in changes in arterial
      pressure. Selective change in the reactivity of alpha 2-adrenoceptors alone was
      revealed in both groups. Stable reduction of vascular alpha 2-adrenergic
      reactivity (by 57-58%) and arterial pressure was recorded in animals with acute
      pancreatitis. In falsely operated on animals, in contrast, the values of these
      indices exceeded the control level. In animals with a functioning central nervous
      system inhibition of alpha 2-adrenergic reactivity correlated with change in
      arterial pressure only in the initial (3-4 hours) hemorrhagic phase of acute
      pancreatitis.

PMID- 1974346
TI  - Isolation, identification and synthesis of locustamyotropin (Lom-MT), a novel
      biologically active insect peptide.
AB  - A peptide that stimulates the spontaneous contractions of the hindgut of
      Leucophaea maderae has been purified from extracts of brain-corpora
      cardiaca/corpora allata-subesophageal ganglion complexes of 9000 adult Locusta
      migratoria and was designated locustamyotropin or Lom-MT. The primary structure
      of this 12 residue peptide has been determined Gly-Ala-Val-Pro-Ala-Ala-Gln-Phe
      Ser-Pro-Arg-Leu-NH2. The C-terminal sequence (Phe-Ser-Pro-Arg-Leu-NH2) is
      identical to the C-terminal pentapeptide of the pheromone biosynthesis activating
      neuropeptide, recently isolated from Heliothis zea, and is also similar to the C
      terminal of leucopyrokinin of Leucophaea. Synthetic Lom-MT showed biological as
      well as chemical characteristics, indistinguishable from those of native Lom-MT.
      In locust preparations, Lom-MT provoked an increase in frequency, amplitude and
      tonus of contractions of the oviduct, but was inactive in the same conditions on
      the locust hindgut preparation.

PMID- 1974347
TI  - Isolation and structural characterization of insulin, glucagon and somatostatin
      from the turtle, Pseudemys scripta.
AB  - The chelonians occupy an important position in phylogeny representing a very
      early branching from the ancestral reptile stock. Hormonal polypeptides in an
      extract of the pancreas of the red-eared turtle were purified to homogeneity by
      reversed phase HPLC and their primary structures were determined. Turtle insulin
      is identical to chicken insulin. Turtle glucagon differs from chicken glucagon by
      the substitution of a serine by a threonine residue at position 16 and from
      mammalian glucagon by an additional substitution of an asparagine by a serine
      residue at position 28. Turtle pancreatic somatostatin is identical to mammalian
      somatostatin-14. The crocodilians are phylogenetically much closer to the birds
      than are the chelonians. Alligator insulin, however, contains three amino acid
      substitutions relative to chicken insulin. Thus, caution is required when
      inferring phylogenetic relationships based upon a comparison of amino acid
      sequences of homologous peptides.

PMID- 1974348
TI  - MIF-1 can accelerate neuromotor, EEG and behavioral development in mice.
AB  - Newborn mice were injected SC daily with 1 mg/kg of MIF-1 or saline during the
      first 19 days of life. The progress of each pup was monitored for physical (body
      weight, eye and ear opening), neurobehavioral (reflexes) and neurophysiological
      (EEG) development until the weaning stage. In early adulthood (40 days of age)
      mice were tested on a maze learning task. Results indicate that MIF-1 can
      accelerate neurologic (days 3-9), somatic (days 10-14) and
      electroencephalographic (days 16-19) parameters, and that the effects of
      treatment last into the early adult stage with increased learning abilities in an
      appetitive task.

PMID- 1974349
TI  - Oxytocin modulation of intrathoracic sympathetic ganglionic neurons regulating
      the canine heart.
AB  - Substance P and vasoactive intestinal peptide are known to activate intrathoracic
      sympathetic neurons which regulate the heart. In the present series of
      experiments, when 1 I.U. of oxytocin in 0.1 cc of normal saline was administered
      into the cranial poles of stellate or the middle of middle cervical ganglia
      cardiac rate and force were augmented. The locations of ganglionic loci which,
      when injected, resulted in cardiac changes varied between animals. Twenty active
      sites were identified in the 12 dogs investigated. When the vehicle (0.1 cc of
      normal saline) was injected into these active sites minimal cardiac responses
      were induced in one instance. When 1 or 2 I.U. of oxytocin was administered into
      the superior vena cave of seven animals slight systemic hypotension occurred in
      two of these animals. Cardiac responses were induced when oxytocin was reinjected
      into active intrathoracic ganglionic sites after whole body administration of
      hexamethonium (10 mg/kg IV), but not after local administration of timolol into
      the ganglia. Thus, it appears that oxytocin can activate intrathoracic ganglionic
      neurons involved in efferent sympathetic cardiac regulation. That such responses
      persist in the presence of nicotinic blockade, but not following beta-adrenergic
      blockade of ganglionic neurons, indicates that oxytocin modifies beta-adrenergic
      and not nicotinic receptors on neurons in these ganglia.

PMID- 1974351
TI  - Lymphocyte subsets and HLA-DR expression in normal pancreas and chronic
      pancreatitis.
AB  - In an attempt to study the mechanisms leading to fibrosis in chronic
      pancreatitis, an in situ immunohistochemical investigation of lymphocytes and of
      class II major histocompatibility complex expression (HLA-DR) by epithelial cells
      has been designed. Samples of normal pancreas (n = 8), chronic calcifying
      pancreatitis (n = 4), chronic obstructive pancreatitis (n = 6), and diffuse
      fibrosing pancreatitis (n = 6) have been studied. In normal pancreas, T
      lymphocytes were rare and were located in the epithelial layer of pancreatic
      ducts and in the periductal connective tissue. Duct cells were constantly HLA-DR
      negative. In chronic calcifying pancreatitis and chronic obstructive
      pancreatitis, T cells were numerous and were located around ducts and in the
      spreading areas of fibrous septa. In chronic obstructive pancreatitis, the duct
      cells strongly expressed the HLA-DR antigen. In diffuse fibrosing pancreatitis,
      fibrous tissue was devoid of lymphocytes and duct cells never expressed the HLA
      class II antigen. These results suggest that lymphocytes are involved in the
      fibrosing process occurring in chronic calcifying pancreatitis and chronic
      obstructive pancreatitis but not in diffuse fibrosing pancreatitis. The
      significance of de novo expression of HLA-DR antigen by duct cells is discussed.

PMID- 1974350
TI  - Occurrence and distribution of putative neurotransmitters in the frog-lung
      parasite Haplometra cylindracea (Trematoda: Digenea).
AB  - The localisation and distribution of the cholinergic, serotoninergic and
      peptidergic components of the nervous system of the frog-lung fluke Haplometra
      cylindracea have been determined by the application of standard enzyme
      cytochemical and immunocytochemical techniques to cryostat sections and whole
      mount preparations. Cholinesterase activity (ChE), as indicative of
      acetylcholine, has been demonstrated cytochemically in the CNS and PNS; however,
      the anterior ganglia were notably unreactive. The occurrence of serotonin was
      examined by an indirect immunofluorescence technique, and immunoreactivity (IR)
      was demonstrable in small, paired anterior ganglia and in fine nerve fibres
      associated with the somatic muscle, cirrus and gonopore. The peptidergic portion
      of the nervous system was investigated using antisera to 17 mammalian regulatory
      peptides and the invertebrate peptide FMRFamide, and was visualised by both
      indirect immunofluorescence and confocal scanning laser microscopy. Positive
      immunostaining occurred with antisera raised against pancreatic polypeptide (PP),
      peptide tyrosine tyrosine (PYY), substance P (SP), peptide histidine isoleucine
      (PHI) and FMRFamide. Immunoreactivity to PP, PYY and FMRFamide was widespread
      throughout the nervous system and was evident in large, paired anterior ganglia,
      the dorsal commissure, main nerve tracts and the extensive array of small fibres
      that constitute the PNS. In contrast, the distribution of nerves immunoreactive
      to SP and PHI was less apparent, with PHI-IR occurring exclusively within the
      fibrous neuropile of the ganglia and in fibres of the ventral nerve cord. Results
      are discussed with respect to the distribution of the various neurochemical
      elements and their roles as putative neurotransmitters and/or regulatory
      molecules.

PMID- 1974352
TI  - Somatostatin: aspects of molecular evolution.

PMID- 1974353
TI  - Electrophysiological analysis of the regulation of endocrine and neuroendocrine
      cells by hormones and transmitters.

PMID- 1974354
TI  - Colocalization of messenger substances with special reference to the hypothalamic
      arcuate and paraventricular nuclei.

PMID- 1974355
TI  - In search of functions for ecdysone in the female insect.

PMID- 1974356
TI  - Gut endocrine cells of invertebrates.

PMID- 1974357
TI  - Vertebrate gut endocrine cells: comparative and developmental aspects.

PMID- 1974358
TI  - Endocrines of insect gut.

PMID- 1974359
TI  - Eicosanoids in corals and crustaceans: primary metabolites that function as
      allelochemicals and pheromones.

PMID- 1974361
TI  - Drug dependence in patients in psychiatric hospitals in Switzerland. A survey
      conducted in nine psychiatric hospitals from 1983-1986.
AB  - The present article forms part of an investigation which has been carried on
      continuously under the auspices of the Conference of Swiss Sanitary Directors
      with the aim of providing evidence on the frequency of drug dependence in
      inpatients of psychiatric hospitals. The investigation is an important source of
      information concerning trends in drug dependence patterns. In this study, it was
      possible to observe a change in preference with regard to the use of analgetic
      compounds over the past years. The decreasing use of barbiturates was found to
      have been replaced by an increased intake of benzodiazepines. Dependence on
      heroin has increasingly been observed in recent years. On the whole, multiple
      drug dependence combined with alcoholism are at present the most frequently
      observed forms of dependence.

PMID- 1974360
TI  - Neuroendocrine and endocrine correlates of pair bonds and parental care in the
      seasonal reproductive cycle of the Siberian hamster (Phodopus sungorus).

PMID- 1974362
TI  - Lactate induced panic and beta-2 adrenergic activation.

PMID- 1974363
TI  - Lawnmower injuries in children: destructive and preventable.

PMID- 1974364
TI  - Peripheral blood mononuclear cell subsets during Trichinella spiralis infection
      in pigs.
AB  - The immune response of 'Yugoslav meat breed' pigs inoculated with low doses of
      Trichinella spiralis muscle larvae was followed over two to nine weeks of primary
      infection, by analysing changes in peripheral blood mononuclear cell subsets, the
      development of a humoral antibody response and muscle larvae burden. During the
      course of the infection, infected animals showed a persistent elevation of both
      CD4+ and CD8+ T cell subsets from days 15 to 60 after the parasite exposure.
      During this time, the number of peripheral blood mononuclear cells expressing
      major histocompatibility complex class II antigens was also increased, while no
      significant differences were found in the number of circulating
      monocytes/macrophages and B cells over time. Humoral antibody responses to muscle
      larvae excretory-secretory products were evident as early as 41 days after
      infection, while the muscle larvae were recovered as early as 27 days after
      infection. The increased levels of CD4+ and CD8+ T cell subsets, as well as cells
      expressing major histocompatibility complex class II antigens in pigs exposed to
      T spiralis, may be indicative of some considerable alterations in cell subsets
      that are involved in the regulation of the swine immune response to this
      parasite.

PMID- 1974365
TI  - Inhibition of CD18-dependent neutrophil adherence reduces organ injury after
      hemorrhagic shock in primates.
AB  - Neutrophil adherence or aggregation may be important in the development of organ
      injury after hemorrhagic shock. Monoclonal antibody (MAb) 60.3 prevents both
      adherence and aggregation. Therefore we investigated MAb 60.3 treatment in
      prevention of organ injury after hemorrhagic shock in rhesus monkeys (Macaca
      mulatta). We performed esophagogastroscopy and placed catheters to measure
      cardiac output, mean arterial pressure, arterial blood gases, and urine output.
      Blood was removed to decrease CO to 30% of baseline for 90 minutes. Just before
      resuscitation, MAb 60.3 (2 mg/kg) or saline solution (control) was administered
      intravenously. Monitoring and fluid resuscitation continued for 24 hours, with
      lactated Ringer's solution given as a maintenance infusion (4 ml/kg/hr) plus
      additional lactated Ringer's solution to maintain CO at preshock levels.
      Esophagogastroscopy was repeated 24 hours after shock. There were two deaths in
      the control group at about 72 hours and none in the MAb 60.3 group. MAb 60.3
      treated animals required less fluid (9.6 +/- 8.8 ml/kg vs 263.8 +/- 225.7 ml/kg),
      gained less weight (0.08 +/- 0.11 kg vs 0.70 +/- 0.37 kg), and maintained a
      higher hematocrit level (35.0% +/- 1.0% vs 26.9% +/- 4.9%). All five control
      animals had gastritis; MAb 60.3-treated animals had none (p less than 0.05;
      Fisher's exact test). Inhibition of neutrophil adherence or aggregation with MAb
      60.3 at the time of resuscitation reduces fluid requirements and gastric injury
      in monkeys after hemorrhagic shock.

PMID- 1974366
TI  - Superiority of substrate enhancement over oxygen free-radical scavengers during
      extended periods of cold storage for cardiac transplantation.
AB  - When cold storage techniques used in cardiac transplantation are extended beyond
      3 hours, there is significant depression in ventricular function. This study was
      undertaken to determine whether the addition of the amino acid L-glutamate or the
      oxygen free-radical scavengers superoxide dismutase (SOD) and catalase (CAT)
      during extended periods of cold storage would improve ventricular function.
      Fifteen rabbit hearts were placed on a Langendorff apparatus, arrested with
      crystalloid potassium cardioplegia, stored in iced saline solution (3 degrees C)
      for 5 hours, and then reperfused at 37 degrees C for 1 hour. In five hearts L
      glutamate (4 mmol/L) was added to the cardioplegic and reperfusate solutions, and
      five hearts received SOD (1500 units/kg/L) and CAT (3500 units/kg/L), whereas in
      five others the cardioplegic and reperfusate solutions were unmodified. Hearts
      treated with L-glutamate had the best recovery of positive dP/dt (79%* glutamate
      vs 49%* SOD and CAT vs 36% unmodified), negative dP/dt (76%* glutamate vs 53% SOD
      and CAT vs 45% unmodified), developed pressure (67%* glutamate vs 51% SOD and CAT
      vs 45% unmodified), and coronary flow (81%* glutamate vs 79%* SOD and CAT vs 62%
      unmodified). We conclude that substrate enhancement with L-glutamate provides
      superior myocardial protection than is possible with the oxygen free-radical
      scavengers SOD and CAT during extended periods of cold storage for cardiac
      transplantation.

PMID- 1974367
TI  - [Neuroleptics in psychogeriatrics. Evaluation of a treatment proposal].
AB  - Based on the receptor-binding profiles and a number of pharmacokinetic
      considerations, five neuroleptic drugs (haloperidol, bromperidol, pipamperone,
      zuclopenthixol and droperidol) were selected for use in different clinical
      situations in a psychogeriatric nursing home of 250 patients in 1984. In December
      1988 an evaluation of this policy showed that on average 31% of the nursing home
      population were prescribed maintenance therapy of neuroleptic medication. When
      comparing the group of patients on neuroleptic medication with the total
      population no difference could be demonstrated in sex, age or psychiatric
      diagnosis, but there was a difference with respect to the three levels of
      disability. Psychosis and behavioural disturbances diminished to a manageable
      level in 69% of the patients. Drowsiness, orthostatic hypotension and
      anticholinergic effects were either not or not more often observed than in a
      group of control patients. Parkinsonism was observed more often, but not
      accompanied with a worse mobility or a higher falling rate. The treatment
      schedule utilized proved to be effective and safe.

PMID- 1974368
TI  - How the messenger got its tail: addition of poly(A) in the nucleus.
AB  - Most mRNAs end in a poly(A) tail, the addition of which is catalysed by a poly(A)
      polymerase in conjunction with a distinct factor that provides specificity for
      mRNAs. The reaction is dynamic, involving separable initiation, elongation and
      termination phases. A companion article in next month's TIBS will review the
      regulation of poly(A) addition and removal during early animal development.

PMID- 1974369
TI  - Soluble suppressive molecule released by human T lymphocytes induced by heat
      inactivated allostimulator cells in the presence of cyclosporine.
AB  - E-rosette-positive peripheral blood lymphocytes (E+PBL) stimulated initially with
      heat-inactivated allogeneic lymphoblastoid cells in the presence of cyclosporine
      (CsA/HI) produce a soluble molecule that suppresses fresh lymphocytes in a
      primary mixed lymphocyte reaction. Cell lines were derived from the E+PBL cells
      after one and two weeks of culture. These lines were CD4+ by both FACS and mRNA
      analysis. The cells produce a potent soluble molecule (supernates often
      containing greater than 1000 units of suppressive activity per milliliter). The
      factor has an apparent molecular weight of 90 k and is sensitive to both pH and
      boiling. The molecule is not the suppressive cytokine TGF beta, based on
      neutralization with anti-TGF beta antibody and mRNA expression. None of the
      available cytokines expressed by these cells was suppressive when titrated into
      an MLR, alone or in combination. These results support the conclusion that CsA/HI
      activated T cell lines produce a novel cytokine that is not antigen-specific or
      MHC-restricted.

PMID- 1974370
TI  - The sigma enigma: biochemical and functional correlates emerge for the
      haloperidol-sensitive sigma binding site.

PMID- 1974371
TI  - Further heterogeneity of the beta-adrenoceptor. The phenylethanolaminotetralines:
      new selective agonists for atypical beta-adrenoceptors.

PMID- 1974372
TI  - Factors influencing the adherence of strains of Streptococcus bovis and
      Escherichia coli isolated from ruminal epithelium.
AB  - Two strains of Streptococcus bovis (A1 and A5) and one strain of Escherichia coli
      (0141:H28) isolated from the surface of bovine ruminal mucous epithelium were
      examined for adherence to isolated and cultured ruminal epithelial cells. The E.
      coli adhered to the target cell by means of fimbriae, which had several common
      properties with type 1 common fimbriae and caused mannose-sensitive
      haemagglutination. The A1 strain of S. bovis was devoid of fimbriae and its
      adherence to the epithelial surface was not inhibited by treatment with sugars or
      phenol-treated bacterial membrane from the same organism. It was therefore
      postulated that the bacterial glycocalyx of the S. bovis organisms acted as
      ligand. The extent of bacterial adherence depended on the state of
      differentiation of the target cell in both the isolated and the cultured ruminal
      cell systems. The receptors for both adherent bacterial species were in all
      probability associated with the glycocalyx of the target cells.

PMID- 1974373
TI  - [The effect of cardioactive drugs on the proteolytic activity of the rat heart
      muscle].
AB  - Cardioactive drugs--beta-adrenoblocking agents (propranolol, trasicor and
      cordanum) and Ca2(+)-antagonists (nifedipine and phenoptine)--exhibited both
      activating and inhibitory effects on proteolytic activity in rat heart tissue
      extract. The beta-adrenoblocking agents did not affect distinctly the activity of
      partially purified cathepsin D and Ca2(+)-dependent neutral protease from
      myocardium. Nifedipine inhibited cathepsin D by 50% and Ca2(+-dependent neutral
      protease--by 75%; phenoptine inhibited also the latter enzyme by 30%.

PMID- 1974374
TI  - [Most assistants have received their certification].

PMID- 1974375
TI  - [Changes in the correlations of the different indices of the entire behavior of
      dogs under the influence of seduxen].
AB  - During chronic use of seduxen various changes of correlation connections between
      different parameters of general behaviour are revealed in dogs. The character and
      degree of expressiveness of these changes depend on the drug dose and typological
      characteristics of animals. The most general and significant manifestation of
      favourable effect of the drug action on animals behaviour is an increase of the
      number of "strong" correlation connections (correlation coefficient is more than
      0.7) of the parameters of various components of conditioned activity, reflecting
      the state of inner inhibition processes, and to the parameters of vegetative
      provision of conditioned reactions. The character of reconstructions of
      correlation connections between different conditioned, vegetative,
      neurotransmitter and general behaviour parameters allows to judge of the
      direction of pharmacological influence on separate functional systems and the
      behaviour as a whole.

PMID- 1974376
TI  - [The effect of prolyl-leucyl-glycinamide on behavioral and visceral functions in
      dogs].

PMID- 1974377
TI  - Immunological reactions of pigs during long-term beta-adrenergic treatment.
AB  - Experiments were performed to determine the effects of the beta-adrenergic
      agonist Ro 16-8714 on the immune system of finishing pigs fed an adequate or a
      low-protein diet. Growth rate, nitrogen and fat retention, body composition as
      well as spleen weight were influenced by both beta-agonist and/or protein level,
      as expected. However, lymphocyte stimulation with Concanavalin A and
      phytohemagglutinine in vitro or in vivo antibody production against horse red
      blood cells were not changed by the beta-agonist in pigs fed sufficient or
      insufficient amounts of protein.

PMID- 1974378
TI  - [Comparative study of TRBC receptor and E receptor on T lymphocytes of human and
      macaque].
AB  - In 1985, rosette formation of human and macaque pan-T lymphocytes with tree shrew
      red blood cells (TRBC) (TRBC rosette) was first found by Ben K et al, showing
      different physico-chemical properties from that of rosette formation with sheep
      red blood cells (E-rosette). In order to approach the correlation between TRBC
      receptor, E receptor (CD2) and other differentiation antigens (CDs) on T
      lymphocytes, rosette inhibition assay and antigenic modulation or co-modulation
      were performed with monoclonal antibodies (McAbs) to CDs, and the distribution of
      TRBC receptor in other peripheral immunocytes, cell lines was also examined. TRBC
      rosette appeared in 88.8% of E rosette positive peripheral blood lymphocytes
      (E(+)-PBL) and in 4.16% of E(-)-PBL. TRBC receptor was also found on all T cell
      lines tested (CEM, H33 HJ-JA 1, Jurkat, MLA-144, Molt-3, Molt-4, Molt-4 clone 8,
      PEER) and some myeloid lines (U 937 and HL 60), but not on human granulocytes, B
      cell lines (Daudi, Raji and Reh) and myeloid line K 562. The modulation or co
      modulation of CD 3, TCR, CD 5, CD 6 and CD 7 with McAbs OKT 3, T 108 (F 1), T 136
      (F 101-15), T 149 (M-T 604) and T 152 (7 G 5) did not affect TRBC rosette
      formation of PBL. TRBC rosette of human and rhesus monkey PBL was not inhibited
      by T 11.1 McAb OKT 11 (CD 2 McAb), in contrast human and rhesus monkey E rosette
      formations were obviously blocked at inhibition rates of 77.9% and 49.3%,
      respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1974379
TI  - Differentiation gradient of dopaminergic neurons in substantia nigra of rat.
AB  - The chemical differentiation featured by the appearance of tyrosine hydroxylase
      (TH) and the distribution pattern of the dopaminergic cells of rat substantia
      nigra (SN) were studied with combined immunocytochemical and electronmicroscopic
      techniques. Under the light microscope, the earliest TH-positive cells at
      embryonic day 13 are localized at the ventral part of rostral midbrain. Later
      appearing TH-positive cells join the earlier ones dorsally and caudally. As to
      the stain intensity and morphology of the labeled cells in the region of the SN,
      there exists a ventral to dorsal and lateral to medial spatiotemporal gradient,
      namely the cells in the ventral and lateral parts, compared with the dorsal and
      medial ones, have more intense staining, larger cell bodies with smaller nuclei
      and more and longer processes. The earliest nigrostriatal projection fibers stem
      from the most laterally located SN cells. Under electron microscope, rough
      endoplasmic reticula are always seen within the positively stained cells. With
      the progression of development, the cells show more intense staining and contain
      more rough endoplasmic reticula and other organelles. Together with the results
      reported on the neurogenesis and migration of the SN cells, the present study
      indicates that the chemical differentiation of SN cells, with a spatiotemporal
      gradient, starts after the completion of cell migration, a process paralleling to
      their morphological differentiation.

PMID- 1974380
TI  - Is the combination between beta-blockers and calcium antagonists appropriate in
      the management of angina pectoris?

PMID- 1974381
TI  - Drug prophylaxis for migraine headaches.
AB  - Drug prophylaxis of migraine headaches is not indicated for all patients;
      however, it may be useful for patients who experience considerable disruption of
      their daily lives because of migraine attacks. To be most effective, drug
      prophylaxis should be one component of a comprehensive approach that includes
      avoidance of precipitating factors, improvement in coping skills and, for most
      patients, increased exercise. The prophylaxis regimen should be individually
      tailored for each patient. Both physician and patient need to determine whether
      the benefit of prophylaxis outweighs the inconvenience and possible side effects
      of the medication used. Beta-adrenergic blocking drugs, notably propranolol, are
      most frequently chosen for prophylaxis. Other effective agents include tricyclic
      antidepressants, calcium channel blockers and nonsteroidal antiinflammatory
      agents, particularly naproxen.

PMID- 1974382
TI  - Pulmonary effects of long-term beta 2-blockade in healthy subjects: comparative
      study of metoprolol OROS.
AB  - The effects on airway response of metoprolol OROS (oral osmotic) and three other
      long-acting beta-adrenoceptor blockers were studied. This was a placebo
      controlled, randomized, five-period, single-blind, crossover trial in 15 healthy
      volunteers. Bronchial beta-blockade was estimated as the displacement of the
      salbutamol bronchodilator response of specific airway conductance (SGAW) measured
      by whole-body plethysmography. Metoprolol OROS (14/190 mg), slow-release (SR)
      metoprolol (200 mg), atenolol (100 mg), long-acting (LA) propranolol (160 mg),
      and placebo were given once daily for 7 days. Inhaled salbutamol was administered
      at peak drug levels in cumulative doses of 12.5 to 800 micrograms on day 5 and in
      a single dose of 400 micrograms on day 7. On day 5, salbutamol induced
      significant increases in SGAW in each treatment group. SGAW increased after the
      single dose of salbutamol on day 7 in all groups and then declined steadily. The
      highest values were found after placebo and metoprolol OROS, with smaller
      increases after SR metoprolol, atenolol, and LA propranolol, the latter showing
      the smallest increase. Therefore, it would appear that under steady-state
      conditions, beta 2-bronchial receptors are least blocked by metoprolol OROS,
      followed by SR metoprolol, atenolol, and LA propranolol.

PMID- 1974383
TI  - Hierarchical pattern of mucosal candida infections in HIV-seropositive women.
AB  - PURPOSE: Candida is the most common cause of opportunistic mucosal infections in
      human immunodeficiency virus (HIV)-positive women. We had observed an apparent
      correlation between the severity of immunodeficiency and the site of mucosal
      candida infection. The current study was designed to determine whether
      significant correlations existed between the sites of mucosal candida infection
      and the degree of immunodeficiency, as determined by subsets of lymphocyte
      populations. PATIENTS AND METHODS: The subjects in this study are 66 HIV
      seropositive women evaluated by members of the Brown University Acquired
      Immunodeficiency Syndrome (AIDS) Program during the 3-year period, September 1,
      1986, through August 30, 1989. All patients had thorough clinical evaluations and
      relevant laboratory studies at defined intervals. All patients with CD4
      lymphocyte counts below 0.2 X 10(9)/L received zidovudine therapy as soon as it
      became available. After July 1988, all patients with CD4 counts below 0.2 X
      10(9)/L received prophylaxis against Pneumocystis carinii pneumonia. All patients
      were counseled about HIV infection, its modes of transmission, and the early
      symptoms of opportunistic infections. RESULTS: The longitudinal data demonstrated
      that candida often infected vaginal mucosa when there was no significant
      reduction in CD4 lymphocyte counts. Candida infection of the oropharyngeal mucosa
      was associated with highly significant reductions in CD4 lymphocyte counts.
      Esophageal candidiasis occurred only with advanced immunodeficiency associated
      with CD4 counts below 0.1 X 10(9)/L. CONCLUSIONS: Candida mucosal infections
      occur in a hierarchical pattern in women with HIV infection. Determination of the
      basis for the differences in susceptibility to candida of the vaginal,
      oropharyngeal, and esophageal mucosal surfaces will require further studies.

PMID- 1974384
TI  - Hemorrhagic fever with renal syndrome imported to Hawaii from West Germany.

PMID- 1974385
TI  - The effects of marital status and partner support on rape trauma.
AB  - Psychological functioning within the first four weeks after rape was compared for
      married and single victims. Marital status did not significantly affect
      psychological symptoms following the assault. For married women, lack of support
      by the partner--particularly when it was unexpected--was significantly related to
      poor psychological functioning after the rape.

PMID- 1974386
TI  - Pancreatic beta-cell somatostatin receptors.
AB  - The characteristics of somatostatin (SRIF) receptors in rat pancreatic beta-cells
      were investigated using rat islets and the beta-cell line HIT-T15 (HIT). The
      biochemical properties of the SRIF receptors were examined with 125I-labeled des
      Ala-1,Gly-2-desamino-Cys-3-[Tyr-11]- dicarba3,14-somatostatin (CGP 23996). 125I
      CGP 23996 bound to SRIF receptors in HIT cells with high affinity and in a
      saturable manner. The binding of 125I-CGP 23996 to SRIF receptors was blocked by
      SRIF analogues with a rank order of potency of somatostatin 28 (SRIF-28) greater
      than D-Trp-8-somatostatin greater than somatostatin 14 (SRIF-14). To investigate
      the physical properties of the HIT cell SRIF receptor, the receptor was
      covalently labeled with 125I-CGP 23996 using photo-cross-linking techniques. 125I
      CGP 23996 specifically labeled a protein of 55 kDa in HIT cell membranes. The
      size of the SRIF receptor in HIT cells is similar to the size of the SRIF
      receptor labeled with 125I-CGP 23996 in membranes of freshly isolated islets,
      suggesting that the physical properties of SRIF receptors in HIT cells and rat
      islet cells are similar. The binding studies suggest that beta-cells
      predominantly express a SRIF-28-preferring receptor. In freshly isolated islets,
      glucose- and arginine-stimulated insulin release was effectively blocked by SRIF
      28 but not by SRIF-14. SRIF-14 did inhibit arginine-stimulated glucagon secretion
      from freshly isolated islets. The dissociation of the inhibitory effects of SRIF
      28 and SRIF-14 on insulin and glucagon release from freshly isolated islets
      suggests that the two peptides act through different receptors in islets to
      regulate hormone secretion.

PMID- 1974387
TI  - Role of glucagon in disposal of an amino acid load.
AB  - Amino acids stimulate the release of glucagon and insulin. To assess the role of
      aminogenic hyperglucagonemia, we have studied, in healthy young males, the
      effects of basal (less than 100 pg/ml) and high (200-400 pg/ml) plasma glucagon
      concentrations on amino acid metabolism during intravenous infusion (0.5 g.h-1.4
      h) of a mixture of 15 amino acids. Basal plasma glucagon concentrations were
      obtained by infusion of somatostatin (0.5 mg/h) plus glucagon (0.25 ng.kg-1.min
      1) and high plasma glucagon concentrations by infusion of somatostatin plus
      glucagon (3.0 ng.kg-1.min-1) or by infusion of amino acids alone. All studies
      were performed under conditions of euglycemic (83-91 mg/dl) hyperinsulinemia (50
      80 microU/ml). Hyperglucagonemia significantly increased 1) net amino acid
      transport from the extracellular into the intracellular space (by approximately
      4%), 2) net degradation of amino acids entering the intracellular space (by
      approximately 40%), and 3) conversion of degraded amino acids into glucose from 0
      10% (basal glucagon) to 70-100% (high glucagon). Hyperglucagonemia did not affect
      the amount of amino acids excreted in the urine (approximately 4%). We conclude
      that glucagon plays an important role in the disposition of amino acids by
      increasing their inward transport, their degradation, and their conversion into
      glucose.

PMID- 1974388
TI  - Bradykinin attenuates glucagon-induced leucine oxidation in humans.
AB  - Trauma and injury are associated with accelerated protein loss. Counterregulatory
      hormones are possible mediators of this response. In the present study, the
      effect of glucagon and glucagon plus bradykinin on leucine and urea kinetics was
      examined in nine normal volunteers during somatostatin infusion and basal insulin
      replacement. Bradykinin was given because of its prostaglandin-stimulating
      qualities and the potential anabolic action of prostaglandins. Physiological
      hyperglucagonemia elicited a small but significant reduction of total leucine
      flux and rate of urea synthesis. Simultaneously, leucine oxidation increased by
      70%. The simultaneous infusion of bradykinin did not alter glucagon-related
      changes in urea or leucine kinetics. Bradykinin, however, significantly
      attenuated the stimulation of leucine oxidation by glucagon. These results
      suggest that glucagon and tissue factors are involved in controlling leucine
      metabolism in humans.

PMID- 1974390
TI  - Protection of alveolar macrophages from hyperoxia by gamma-glutamyl
      transpeptidase.
AB  - Exposure to hyperoxia causes loss of alveolar macrophage cell function. Toxicity
      was measured as suppression of the respiratory burst stimulated by phorbol
      myristate acetate subsequent to exposure (43.5% depression by 2-h exposure to 5
      atm absolute O2 vs. controls). The presence of extracellular glutathione
      significantly protected these cells (7% loss). gamma-Glutamyl transpeptidase, a
      membrane enzyme with its active site directed outward, was necessary for use of
      extracellular glutathione. This was demonstrated using the gamma-glutamyl
      transpeptidase inhibitor, serine-borate complex, which significantly blocked both
      protection of cells by extracellular glutathione and extracellular glutathione
      dependent synthesis of glutathione. The principal use of glutathione in
      antioxidant defense is as a substrate for glutathione peroxidase. The apparent Km
      for glutathione of glutathione peroxidase of rat alveolar macrophages was
      determined to be 2 mM; however, rat alveolar macrophages have approximately 1.3
      mM intracellular glutathione, which is insufficient for maximal enzymatic
      activity. During hyperoxic exposure, this deficit would probably be more
      significant. Thus the ability of extracellular glutathione along with gamma
      glutamyl transpeptidase activity to provide amino acids for de novo glutathione
      synthesis appears to be a potentially important component of antioxidant defense.

PMID- 1974389
TI  - Control of interdigestive and intraduodenal meal-stimulated pancreatic secretion
      in rats.
AB  - Mechanisms of neural (vagal and cholinergic) and hormonal [cholecystokinin (CCK)]
      control of pancreatic exocrine secretion were studied in basal interdigestive
      conditions and after stimulation by an intraduodenal meal in rats equipped with a
      semichronic pancreatic fistula. Bile was recirculated into the duodenum, and a
      solution of trypsin and electrolytes was continuously infused. Pancreatic
      secretion was compared in control experiments, after vagotomy, and after venous
      infusion of cholinergic and CCK antagonists. Basal pancreatic secretion was
      decreased by atropine, pirenzepine, and hexamethonium and to a lesser extent by
      vagotomy (protein output decreased more than fluid and HCO3- outputs). The CCK
      antagonists L364,718 and lorglumide had no effect on basal interdigestive
      pancreatic secretion. Small doses of atropine (8 and 25 micrograms.kg-1.h-1) did
      not modify the cumulated pancreatic response to the meal, whereas larger doses
      (75 and 225 micrograms.kg-1.h-1) increased it by 40-85%, according to the
      variables. Pirenzepine and hexamethonium did not modify the pancreatic response.
      Vagotomy had no effect on fluid and HCO3- responses and tended to increase
      protein response. L364,718 and lorglumide completely inhibited the protein
      response and decreased the fluid and HCO3- responses by 75 and 40%, respectively.
      L364,718 also suppressed the increased pancreatic response induced by atropine.
      This work confirms the prominent role of neural cholinergic mechanisms in the
      control of basal interdigestive pancreatic secretion in rats. In contrast, the
      pancreatic protein response to an intraduodenal meal depends on CCK, whereas
      fluid and HCO3- responses also depend on other hormonal factors. Our results
      suggest that a muscarinic (probably M3) mechanism can decrease the postprandial
      CCK release independently of the pancreatic feedback control by trypsin.

PMID- 1974391
TI  - Neural control of goblet cell secretion in guinea pig airways.
AB  - We studied the neural control of goblet cell secretion in the lower airways of
      anesthetized guinea pigs using a semiquantitative morphometric technique. The
      magnitude of discharge of intracellular mucus was determined in histological
      sections of the trachea and main bronchi stained for mucus glycoproteins.
      Bilateral electrical stimulation of the cervical vagus nerves induced goblet cell
      secretion. The magnitude of the effect was dependent on the frequency, voltage,
      and pulse width of the stimulus, and the duration of stimulation. At 10 Hz, 5 V,
      and 5 ms for 3 min, there was a 62% decrease in the amount of intracellular mucus
      below that with sham stimulation. The secretion was blocked either by atropine or
      by pretreatment with capsaicin but was not significantly inhibited by idazoxan,
      an alpha-adrenoceptor antagonist. The magnitude of goblet cell discharge in
      animals pretreated with propranolol was intermediate between that in controls and
      that with nerve stimulation, although not significant to either. These results
      demonstrate that goblet cell secretion is under neural control in guinea pig
      airways and suggest that cholinergic, nonadrenergic-noncholinergic, and possibly
      adrenergic neural pathways, may contribute to the secretion.

PMID- 1974392
TI  - The effect of an arenavirus infection on liver morphology and function.
AB  - Patients with severe Lassa fever have high serum levels of liver enzymes. Studies
      of the histology of the liver have shown only minor alterations, seemingly
      insufficient to account for death. Pichinde virus is an arenavirus which causes
      severe illness similar to Lassa fever in strain 13 guinea pigs, but does not
      cause severe illness in man. This can serve as a relatively safe model for
      studying the pathology and pathophysiology of fatal arenaviral infection. We used
      this infection to evaluate the effect of arenavirus on liver morphology and
      function. When guinea pigs were infected with Pichinde virus, all developed
      severe disease and died within 14 days of infection. The animals lost large
      amounts of weight. Higher levels of virus were detected in the liver than in
      serum. Aspartate aminotransferase and alanine aminotransferase were elevated late
      in the course of the disease; no elevations were seen in gamma glutamyl
      transpeptidase or bilirubin. Alkaline phosphatase, initially high in these
      growing animals, was markedly decreased early in infection. Prothrombin time and
      activated partial thromboplastin time were increased late in the disease, and
      decreased levels of Factors VIII and IX were seen relatively early. Fatty
      metamorphosis, indicating problems in lipid processing, occurred by day 11, but
      necrosis was minor and occurred late. Pichinde virus infection results in
      significant alterations in the metabolic and synthetic capacities of the
      hepatocytes early in infection in the absence of significant necrosis.

PMID- 1974393
TI  - Acute versus chronic phenytoin therapy and neuromuscular blockade.

PMID- 1974394
TI  - Dexmedetomidine, an alpha 2-adrenoceptor agonist, reduces anesthetic requirements
      for patients undergoing minor gynecologic surgery.
AB  - The effects of dexmedetomidine, an alpha 2-adrenoceptor agonist, on vigilance,
      thiopental anesthetic requirements, and the hemodynamic, catecholamine, and
      hormonal responses to surgery were investigated in healthy (ASA physical status
      1) women scheduled for dilatation and curettage (D & C) of the uterus. Fifteen
      minutes before induction they received single iv doses of either dexmedetomidine
      (0.5 micrograms/kg; n = 19) or saline (n = 20) in a double-blind fashion.
      Anesthesia was induced with thiopental and maintained with N2O/O2 (70/30%) and
      thiopental. Dexmedetomidine was well tolerated and no serious drug-related
      subjective side-effects or adverse events were observed. The most prominent
      subjective effects were fatigue and decreased salivation. The total amount of
      thiopental needed to perform D & C of the uterus was reduced approximately 30%
      (from 456 +/- 141 mg [mean +/- SD] after saline to 316 +/- 79 mg after
      dexmedetomidine). This was mostly due to a smaller induction dose in the group
      receiving dexmedetomidine. Dexmedetomidine appeared to improve the recovery from
      anesthesia as measured by visual analogue scales (VAS) on fatigue and nausea. The
      plasma concentration of norepinephrine was decreased by 56% after dexmedetomidine
      implying decreased sympathetic nervous activity. Systolic and diastolic blood
      pressure were moderately reduced after dexmedetomidine administration. The
      authors conclude that dexmedetomidine preanesthetic medication decreases
      thiopental anesthetic requirements and improves the recuperation from anesthesia
      with no serious hemodynamic or other adverse effects. Further studies in patients
      undergoing more stressful surgery are indicated.

PMID- 1974395
TI  - Rapid-sequence orotracheal intubation: a comparison of three techniques.
AB  - The authors compared tracheal intubating conditions using three techniques for
      rapid-sequence orotracheal intubation. Sixty patients were randomly assigned to
      one of three groups: priming with vecuronium (0.01 mg/kg priming dose, 4-min
      priming interval, 0.14-mg/kg intubating dose along with thiopental 4-6 mg iv);
      timing with vecuronium (0.15-mg/kg intubating dose given before thiopental and
      timed to weakness of hand grip); and succinylcholine (1.5 mg/kg). Blinded
      intubators graded intubating conditions 60 s after the induction of anesthesia
      with thiopental. Intubation scores in the succinylcholine group were
      significantly better than in the priming group (P = 0.009). Intubation scores of
      the succinylcholine and the timing groups were not significantly different. Use
      of the timing principle for rapid-sequence orotracheal intubation is a reliable
      alternative in cases where succinylcholine is contraindicated.

PMID- 1974397
TI  - Paralysis after long-term administration of vecuronium.

PMID- 1974396
TI  - Pertussis toxin and 4-aminopyridine differentially affect the hypnotic-anesthetic
      action of dexmedetomidine and pentobarbital.
AB  - Dexmedetomidine, a highly selective and potent agonist at alpha-2 adrenoceptors,
      produces a hypnotic-anesthetic action in rats. The mechanism for this response
      may involve an inhibitory G-protein and increased conductance through a potassium
      channel. To investigate this, the effects of pertussis toxin, a specific
      inactivator of inhibitory G-proteins, and 4-aminopyridine, a blocker of potassium
      channels, on the hypnotic-anesthetic response to dexmedetomidine were studied in
      rats. Pertussis toxin and 4-aminopyridine both decreased the hypnotic-anesthetic
      action of dexmedetomidine in a dose-dependent fashion. To preclude the
      possibility that pertussis toxin and 4-aminopyridine attenuated the hypnotic
      anesthetic action of dexmedetomidine via indirect central nervous system
      excitation, the effects of pertussis toxin and 4-aminopyridine on the hypnotic
      anesthetic action of pentobarbital also were assessed. Pentobarbital-induced
      hypnosis was not attenuated by either treatment. These results suggest that the
      receptor-effector mechanism for the hypnotic-anesthetic action of dexmedetomidine
      involves an inhibitory G-protein and increased conductance through a potassium
      channel.

PMID- 1974398
TI  - Response of acute asthma to a beta 2 agonist in children less than two years of
      age.
AB  - The management of the young asthmatic child is still controversial and it has
      been questioned whether the infant and very young child with asthma respond to
      beta 2 agonists. We studied the response to nebulized beta 2 agonists in 43
      children under the age of 2 years who presented to the emergency room with acute
      asthma. Clinical score and oxygen saturation were determined on admission to the
      emergency room and at least 30 minutes after each inhalation. The clinical score
      was defined as the sum of five variables (heart rate, respiratory rate, dyspnea,
      accessory muscle use, and wheezing), each graded as 0 or 1. The mean clinical
      score improved significantly after nebulized albuterol (mean +/- SD, 3.75 +/- 1.2
      versus 2.80 +/- 1.65, P less than .01). Mean oxygen saturation did not change
      significantly (mean +/- SD, 94.8% +/- 2.85 versus 95.2% +/- 2.54). Only three
      patients had a decrease in arterial oxygen saturation of greater than 2% (3% in
      each one of them) following bronchodilator therapy. Our results suggest beta 2
      inhalation to be beneficial to the majority of asthmatic children younger than 2
      years of age and safe to administer. The combination of clinical score and oxygen
      saturation provides a simple noninvasive method of monitoring the response to
      therapy in young children with acute asthma.

PMID- 1974399
TI  - Compared peripheral H1 inhibiting effects of cetirizine 2 HCl and loratadine.
AB  - Histamine-induced wheals and flares were measured in seven healthy volunteers
      zero, four, and eight hours after oral intake of cetirizine, 2.5, 5, and 10 mg;
      loratadine, 10, 20, and 40 mg; and placebo. Cetirizine (2.5, 5, and 10 mg) and
      loratadine (20 and 40 mg) significantly inhibited the histamine-induced wheals at
      all experimental times and with all histamine concentrations. This was not always
      the case with loratadine, 10 mg. Cetirizine, 2.5 mg, was as potent in inhibiting
      the histamine skin reactivity as loratadine, 10 mg.

PMID- 1974400
TI  - Peripheral T-cell subset imbalance in patients with vitiligo and in their
      apparently healthy first-degree relatives.
AB  - Twenty-two patients with vitiligo had lesions stable for at least 1 year and 23
      apparently healthy first-degree relatives were studied for T-cell subpopulations
      using monoclonal antibody technique. High levels of CD4+ lymphocytes and high
      CD4/CD8 ratios were found in both patients and their relatives, as compared with
      normal age-matched and sex-matched controls. This immunologic abnormality,
      together with the presence of autoantibodies previously reported in the
      apparently normal relatives, seems to be the hallmark of the disease. Further
      support of this interpretation comes from the observation that two out of the 23
      apparently healthy relatives went on to develop vitiligo in a 2-year follow-up.

PMID- 1974401
TI  - Efficacy of cetirizine in the treatment of seasonal allergic rhinoconjunctivitis.
AB  - The efficacy of cetirizine, 10 mg once daily, in the treatment of seasonal
      allergic rhinoconjunctivitis was evaluated in a double-blind placebo-controlled
      trial. Sixteen patients monosensitized to olive pollen were treated
      simultaneously for 6 weeks, including one pollen season. Severity of symptoms and
      rescue drug consumption were significantly lower in the cetirizine group.

PMID- 1974402
TI  - Levocabastine versus cromolyn sodium in the treatment of pollen-induced
      conjunctivitis.
AB  - Thirty patients with allergic conjunctivitis, caused by Parietaria or grass
      pollens, participated in a double-blind parallel study comparing levocabastine to
      cromolyn sodium, both given as eye drops. Symptom and sign scores were recorded
      during a 4-week period. The patients received only these drugs during the time of
      observation. The evaluation of the clinical signs and symptoms by the clinicians
      and by the patients revealed a significant improvement of conjunctivitis in all
      patients. The intergroup comparison was equal in the two groups treated
      respectively with levocabastine and cromolyn. Therefore, levocabastine and
      cromolyn are effective in the treatment of pollen-induced allergic
      conjunctivitis.

PMID- 1974404
TI  - The protean manifestations of hemorrhagic fever with renal syndrome. A
      retrospective review of 26 cases from Korea.
AB  - Twenty-six cases of hemorrhagic fever with renal syndrome from 1981 to 1986 were
      retrospectively reviewed to determine the scope of clinical presentation and the
      unique complications of the illness. The diagnosis was confirmed by detection of
      Hantaan virus antibody in 25 cases and by characteristic autopsy findings in 1
      case. The illness could be classified into three distinct clinical subgroups.
      Fever was universally present. Two patients presented with intractable shock and
      diffuse hemorrhage and died within 6 days from multi-organ system failure,
      mimicking the clinical picture of overwhelming sepsis. Eighteen patients
      presented with acute renal failure with an illness lasting a mean of 21 days
      (range, 10 to 36 days). Resolution of thrombocytopenia heralded recovery of renal
      function. At discharge, the serum creatinine level was normal in 13 patients; 5
      patients had evidence of minimal renal dysfunction. Acute pulmonary edema
      requiring hemodialysis and retroperitoneal hemorrhage were the major
      complications in this subgroup. Six patients had an undifferentiated febrile
      illness with normal renal function. Fever, thrombocytopenia, abnormal urinalysis,
      hypertransaminasemia, and a benign clinical course characterized the third
      clinical pattern. The recent availability of serodiagnostic methods to detect
      Hantavirus group antibody facilitates the diagnosis of hemorrhagic fever with
      renal syndrome. Application of this test in the described clinical settings will
      identify unsuspected cases, broaden the knowledge of the geographic distribution
      of Hantavirus infection, and increase physician awareness of its protean
      manifestations.

PMID- 1974403
TI  - Sulfated polysaccharides prevent human leukocyte elastase-induced acute lung
      injury and emphysema in hamsters.
AB  - Studies were designed to explore the possibility that sulfated polysaccharides
      had the potential to prevent human leukocyte elastase (HLE)-induced lung injury.
      Arteparon (GAGPS), heparin, heparan sulfate, chondroitin sulfate, and dextran
      sulfate, but not dextran, inhibited HLE-mediated hydrolysis of succinyl-ala2-val
      pNA. GAGPS, used as a paradigmatic sulfated polysaccharide, was a potent
      inhibitor of elastolysis in vitro. GAGPS given intratracheally prevented acute
      injury and emphysema in hamsters when administered up to 8 h before HLE
      insufflation. The results suggest that sulfated polysaccharides may be potent
      inhibitors of HLE-mediated lung injury.

PMID- 1974405
TI  - Histamine stimulation of mucociliary activity in the rabbit maxillary sinus.
AB  - The in vivo effect of histamine on mucociliary activity in the rabbit maxillary
      sinus was investigated by injecting histamine into the maxillary artery and
      recording the responses with a photoelectric technique. Histamine stimulated the
      mucociliary activity dose-dependently in the dose range 10 to 1,000
      micrograms/kg. The maximum response was 31.6% +/- 3.7% at a dose of 50
      micrograms/kg. The histamine-induced stimulation of the mucociliary activity was
      characterized by a short latency with a peak response within 1 to 2 minutes and a
      slow decline lasting about 5 minutes. The response displayed tachyphylaxis.
      Cholinergic blockade with atropine did not affect the response to histamine.
      Blockade of H1 receptors with pyrilamine abolished the response to histamine,
      whereas blockade of H2 receptors with cimetidine was without effect. The H2
      agonist dimaprit failed to stimulate the mucociliary activity. It is concluded
      that histamine stimulates the mucociliary activity in the rabbit maxillary sinus
      via H1 receptors.

PMID- 1974407
TI  - Regional localization of polymorphic markers on chromosome 10 by physical and
      genetic mapping.
AB  - The human vimentin gene and a random DNA segment (D10S39) were mapped to the
      short arm of human chromosome 10 by linkage analysis. A panel of somatic cell
      hybrids and monosomy cell-lines, which divide chromosome 10 into seven regions,
      was used to localize 10 polymorphic markers on this chromosome. The physical map
      locations obtained correlate well with linkage maps of chromosome 10. Two markers
      which have been shown to be closely linked to the gene for multiple endocrine
      neoplasia type 2A map distal to a translocation breakpoint in band 10q11.2.

PMID- 1974408
TI  - The polymorphic human DNA sequence D8S8 assigned to 8q13-21.1, close to the
      carbonic anhydrase gene cluster, by isotopic and nonisotopic in situ
      hybridization and by linkage analysis.
AB  - Restriction fragment length polymorphism at the D8S8 locus is explained by the
      occurrence of at least two alternative alleles at two separate TaqI sites; TaqI-A
      allele frequencies 0.73 and 0.27 and TaqI-B allele frequencies 0.94 and 0.06. The
      D8S8 locus has been assigned to 8q13-21.1, near to the carbonic anhydrase (CA)
      gene cluster, by in situ hybridization to metaphase chromosomes using both
      tritium and immunofluorescently labelled probes. Linkage analysis using the CEPH
      family DNA panel indicates a close genetic linkage between D8S8 and CA3, with a
      lod score of +7.80 at theta = 0.05 in males.

PMID- 1974406
TI  - Phagocytes, toxic oxygen metabolites and inflammatory bowel disease: implications
      for treatment.
AB  - Phagocytic cells are prominent in the inflammatory infiltrate of Crohn's disease
      and ulcerative colitis. These cells secrete a variety of agents which are thought
      to be important in the pathogenesis of tissue damage in inflammation. The
      function of phagocytic cells does not appear to be impaired in inflammatory bowel
      disease, and certain aspects, including toxic oxygen metabolite production, are
      enhanced in circulating monocytes and tissue phagocytes isolated from the
      inflammatory site. 5-Amino-salicylic acid, used in the treatment of inflammatory
      bowel disease, is a specific scavenger of hypochlorite, a toxic metabolite of
      oxygen produced by phagocytic cells. These findings suggest that phagocytic cells
      play an important role in the pathogenesis of tissue damage in inflammatory bowel
      disease. The future development of pharmacological agents which modify specific
      aspects of phagocyte function, or act as scavengers of toxic oxygen metabolites
      produced by these cells, may provide more effective treatment for these
      conditions.

PMID- 1974409
TI  - Gaucher disease associated with a unique KpnI restriction site: identification of
      the amino-acid substitution.
AB  - In an earlier survey of the glucocerebrosidase locus using 20 restriction enzymes
      and a 1039 bp probe we found that 1 of 9 Gaucher disease patients had a unique
      pattern with KpnI. a pattern that was not observed in any other Gaucher patient
      or in 31 controls. We have now localized the mutation in this patient to a T----A
      transversion in nucleotide 764 of the cDNA occurring on one of the two
      glucocerebrosidase alleles. The presumed abnormality in the other allele has not
      been identified. The deduced amino-acid change in the allele with the mutation at
      nucleotide 764 is a relatively drastic alteration of amino acid 255 from
      phenylalanine to tyrosine. The genomic DNAs of 31 other Gaucher disease patients
      (representing 62 Gaucher disease alleles) were examined for this mutation using
      the polymerase chain reaction. None were found to have this abnormality.

PMID- 1974410
TI  - Expression of multiple drug resistance gene, MDR1, and N-myc oncogene in an
      Italian population of human neuroblastoma patients.
AB  - Thirty-four patients of an Italian population affected by neuroblastoma (NB) were
      evaluated at diagnosis for multidrug resistance gene (MDR1) and N-myc oncogene
      amplification. No patients showed MDR1 amplification, while extra copies of the N
      myc gene were found in 9 out of 34 patients (26%). N-myc amplification was
      correlated (p = 0.008) with a shorter progression-free survival. RNA was purified
      from fresh tumor biopsies and analysed in 29 NB samples. MDR1 gene expression was
      found to be increased in 5 out of 29 tumor samples at onset (17%) and in 1 out of
      3 at relapse, but none of them expressed both MDR1 and N-myc genes
      simultaneously. No correlation was found between MDR1 or N-myc genes expression
      and tumor progression. MDR1 mRNA transcription may occur spontaneously after
      onset, suggesting that certain NB tumors could be resistant to antineoplastic
      drugs at onset. All 5 patients showing MDR1 mRNA transcription achieved complete
      or partial clinical remission after polychemotherapy. This was presumably due to
      inclusion in the therapeutic protocol of a high dose of Cisplatin, a drug not
      susceptible to the effects of the MDR1 gene product. Our findings show that cells
      which actively transcribe for the MDR1 gene are present in several untreated NB
      patients. No gene amplification was detected and probably the MDR1 gene
      expression is regulated at the transcriptional level.

PMID- 1974411
TI  - [New technic for the treatment of high intraabdominal cryptorchism: testicular
      autotransplantation with venous anastomosis only].
AB  - A new technique in the treatment of high intraabdominal cryptorchidism is
      proposed: testicular autotransplantation with venous anastomosis only. The
      technique consists in performing microsurgical anastomosis of the spermatic vein
      and homolateral inferior epigastric vein only for adequate venous drainage,
      leaving irrigation of testis to the deferential artery alone. We have utilized
      this technique in 16 cases and excellent results have been achieved. It has
      permitted performing surgery in younger patients (2 years). Surgical trauma and
      the duration of the operation are less compared to the Silber technique. There is
      a higher success rate and the procedure is easy to perform.

PMID- 1974412
TI  - Leucopenia after gold and sulphasalazine treatment.

PMID- 1974413
TI  - HLA-DR antigens and HLA-DQ beta chain polymorphism in susceptibility to
      rheumatoid arthritis.
AB  - Forty four patients with rheumatoid arthritis (RA) were studied for HLA-DR
      antigens and for HLA-DQ beta chain gene restriction fragment length polymorphism
      using DNA hybridisation. A significant increase in the prevalence of the DR4
      antigen and a tendency towards an increase of DR1 was found in patients with RA.
      No allelic form of HLA-DQ restriction fragment length polymorphism patterns was
      increased, but the prevalence of an allele characterised by a combination of 7.5
      and 3 kb fragments was decreased among patients with RA. The DQw8 subtype
      represented by a 12 kb fragment was the most common DR4 associated allele, and a
      3.7 kb fragment related to DQw7 was found in only 5/25 (20%) DR4 positive
      patients and 2/12 (17%) controls. The results support the hypothesis that RA
      susceptibility factors are primarily located within HLA-DR genes but HLA-DQ genes
      may have a role in protection from the disease.

PMID- 1974414
TI  - [Aliphatic alpha-amino acids as biologically active compounds].

PMID- 1974415
TI  - [Structural changes in the composition of amplifying sequence AUD-Sr1 of
      Streptomyces rimosus after cloning into Escherichia coli].
AB  - The presence of four EcoRV sites in the composition of the amplifying sequence
      AUD-Sr1 of S. rimosus resulting from its introduction on vector pUC19 into E.
      coli was studied. It was shown that the sequence had no EcoRV sites in a S.
      lividans strain while a number of plasmid and phage DNAs and chromosomal DNA of
      the strain were to be affected by EcoRV. The following regularities were
      observed: practically all the investigated hybrid plasmids from E. coli contained
      EcoRV sites in the composition of the AUD, EcoRV sites were present in strictly
      specified loci of the AUD sequence, appearance of an EcoRV site was accompanied
      by an increase in the size of the AUD fragment which contained it, the inserts
      detected in the SacI-PvuII fragment of the AUD were small in size (0.1 to 0.8 kb)
      and varied in different hybrid plasmids. The following mechanisms are discussed:
      insertion of the E. coli IS element into the AUD-Sr1 and high mutability of the
      amplifying sequence AUD-Sr1 in E. coli.

PMID- 1974416
TI  - Effect of alcohol intake on human apolipoprotein A-I-containing lipoprotein
      subfractions.
AB  - High-density lipoprotein comprises two main types of lipoprotein particles: (1)
      those that contain apolipoproteins A-I and A-II, designated LpA-I:A-II, and (2)
      those that contain apolipoprotein A-I but not apolipoprotein A-II, designated LpA
      I. Both have been extensively studied and are believed to represent distinct
      metabolic entities that may confer differing protection against coronary artery
      disease risk. We have previously suggested that LpA-I might represent the
      antiatherogenic effect, which has been ascribed mainly to its effect on high
      density lipoprotein cholesterol; we set out to investigate, in 344 men, the
      relation between LpA-I:A-II and LpA-I levels and alcohol consumption. As the
      alcohol intake rose, LpA-I:A-II levels increased, while LpA-I levels fell. On the
      assumption that LpA-I is the antiatherogenic fraction of high-density
      lipoprotein, the putative protective action of alcohol consumption against
      coronary artery disease should be reconsidered.

PMID- 1974417
TI  - [The effect of agonists and antagonists of histamine H1- and H2-receptors on the
      growth of Mycobacterium tuberculosis H 37 Ra].
AB  - The influence of histamine H1- and H2-agonists and -antagonists on the growth of
      mycobacteria is described. While compounds which are strongly related to
      histamine improve the growth, predominantly H1-antagonists inhibit bacterial
      growth.

PMID- 1974418
TI  - Inhibitory effect of midaglizole on alpha adrenoceptor agonist-induced
      contractions of canine tracheal smooth muscle.
AB  - To determine why midaglizole is effective in some patients with severe asthma, we
      investigated the inhibitory effects of midaglizole, prazosin or yohimbine on the
      BHT 920-, phenylephrine-, or noradrenaline-induced contractions of canine
      tracheal smooth muscle. After pretreatment with atropine (10(-6) M) and
      propranolol (10(-6) M) and precontraction with serotonin (3 x 10(-7) M), the
      tracheal muscle showed contractile responses to the exogenous administration of
      both alpha 1 and alpha 2 adrenoceptor agonists. Every alpha antagonist inhibited
      these agonist-induced contractions. Inhibitory activity of midaglizole (10(-4) M)
      for the alpha agonists was BHT-920 greater than noradrenaline greater than or
      equal to phenylephrine, while that of prazosin (3 x 10(-6) M) was phenylephrine
      greater than noradrenaline greater than BHT-920. Moreover, yohimbine completely
      inhibited the contractions at the lower concentration of 3 x 10(-7) M than that
      of other two antagonists. Our findings demonstrate that midaglizole dose
      dependently inhibits airway contractions induced by alpha adrenoceptor agonists.

PMID- 1974419
TI  - Mitochondrial respiration in myocardial biopsy samples as a criterion of
      postischemic recovery of the cardiac contractility.
AB  - Isolated perfused guinea pig hearts were arrested by a high K+ cardioplegic
      solution containing (PG group) or lacking (control group) 10 mM phosphocreatine +
      15 mM glutamate. Total normothermic ischemia lasted 45 min followed by 30 min
      reperfusion. Mitochondrial respiration in the absence and presence of different
      concentrations of ADP and creatine was studied in biopsy samples (6-8 mg) after
      saponin treatment. The samples were taken before and after ischemia, as well as
      after the reperfusion period. A slightly better relative recovery of developed
      pressure (RRDP) in PG group was associated with higher mitochondrial acceptor
      control ratio after reperfusion (5.74 +/- 0.32 vs. 4.54 +/- 0.21 in PG and
      control groups, resp., p less than 0.01). When the results obtained in both
      groups were treated together, tight correlations between the pre- or postischemic
      mitochondrial state and RRDP were revealed. Higher values of RRDP were found for
      the hearts with lower preischemic values of (low ADP + creatine)-stimulation of
      mitochondrial respiration (r = -0.57, p less than 0.01). Relative changes in this
      mitochondrial parameter during ischemic period were in a good correlation with
      the RRDP (r = 0.82, p less than 0.001). The data suggest that the study of the
      mitochondrial function in myocardial biopsy samples before ischemia and
      reperfusion could provide a useful information for the prognosis of cardiac
      function recovery.

PMID- 1974421
TI  - Lipoprotein binding of crosslinked type III collagen aminopropeptide and
      fractions of its antigen in blood.
AB  - When [125I] labelled bovine type III collagen aminopropeptide (PIIIP) is
      incubated with tissue transglutaminase (TGase) mixed with hyperlipemic rabbit
      plasma and subjected to ultracentrifugation the labelled fraction with density
      less than 1.2 g/ml is larger than when either lipoprotein or TGase is omitted.
      Chromatography of the fraction with density less than 1.2 g/ml shows the presence
      of peaks which are not present in the denser material. Since their elution
      positions indicate that they have higher molecular weights than PIIIP it is
      concluded that they consist of [125I]PIIIP which had been crosslinked by TGase
      and bound to lipoprotein. Low concentrations of similar low density, high
      molecular weight PIIIP antigens were found in normal human plasma and pooled sera
      from angiography subjects. In two out of seven infarct patients an unusually
      large fraction of the PIIIP antigen in the serum was found in a very high
      molecular weight peak containing low density material. It is speculated that this
      may arise from atherosclerotic lesions.

PMID- 1974420
TI  - Binding and pharmacologic properties of peptides derived from human and rat
      angiotensin II (AII) mRNA.
AB  - We investigated the binding and pharmacologic properties of peptides encoded by
      complementary mRNA derived from the human and rat angiotensinogen gene (human and
      rat IIA, respectively). Human IIA (identical with AII in 4 amino acids) inhibited
      binding of [125I]AII to rat adrenal glomerulosa particles (Ki = 0.62 +/- 0.09
      microM) and competitively blocked, with similar potency, the ability of three AII
      receptor agonists to contract rabbit aorta. Rat IIA affected neither [125I]AII
      binding to glomerulosa particles nor the contractile response of AII. We conclude
      that rat IIA does not interact with AII or its receptors and that human IIA acts
      as a competitive inhibitor of AII at the receptor level.

PMID- 1974422
TI  - Molecular basis of HbE-beta-thalassemia and the origin of HbE in northeast
      Thailand: identification of one novel mutation using amplified DNA from buffy
      coat specimens.
AB  - Amplification of DNA via polymerase chain reaction directly from a small amount
      of a buffy coat fraction was used to study the molecular basis of HbE-beta
      thalassemia in the northeastern Thai population. Eight different mutations
      including the new one causing a beta o-thalassemia phenotype were detected. This
      novel mutation is an amber mutation at codon 26, which occurs at the same
      position as that of HbE; the most common hemoglobin variant in Southeast Asian
      countries. A pitfall in detection of the HbE mutation by restriction enzyme
      analysis was pointed out and differential diagnosis of the HbE mutation and the
      novel one by using allele specific oligonucleotide probes were described.
      Analysis of polymorphic restriction sites in the beta-globin gene cluster
      containing the beta E gene revealed two previously undescribed haplotypes in the
      Southeast Asian populations, which provide evidence for the multiple origins of
      beta E gene in Southeast Asian populations.

PMID- 1974423
TI  - Non-adrenergic sites for imidazolines are not directly involved in the alpha 2
      adrenergic antilipolytic effect of UK 14304 in rat adipocytes.
AB  - The binding of the alpha 2-agonist [3H]UK 14304 on Wistar rat adipocyte membranes
      was separated in two distinct components: one was displaceable by adrenaline or
      other alpha 2-adrenergic agents and possessed the characteristics of alpha 2
      adrenoceptors while the other, non-adrenergic in nature, was only recognized by
      some imidazoline derivatives [3H]idazoxan binding shared the same
      characteristics. The non-adrenergic sites labeled by both radioligands are
      similar to those described for [3H]idazoxan on other tissues such as brain
      cortex, smooth muscle and kidney. Even though they were about 10-fold more
      numerous than the true alpha 2-adrenoceptors, the non-adrenergic binding sites
      were not directly involved in the antilipolytic action of UK 14304 since alpha 2
      antagonists devoid of interaction with these sites (yohimbine, phentolamine)
      totally blocked the UK 14304 effect. However, the existence of such a type of
      site impairs direct quantification of alpha 2-adrenoceptors in rat adipocytes.
      The use of [3H]RX 821002 (2-(2-methoxy-1,4-benzodioxan-2yl)imidazoline) allowed
      an accurate quantification of rat adipocyte alpha 2-adrenoceptors (Bmax = 35 +/-
      2 fmol/mg protein, Kd = 2.6 +/- 0.6 nM) since it did not interact with non
      adrenergic binding sites and exhibited the highest alpha 2-blocking properties
      among the various alpha 2-antagonists tested. [3H]RX 821002 binding analysis
      revealed that alpha 2-adrenoceptors are, on rat adipocytes; (i) less numerous
      than in other species well known for their alpha 2-adrenergic inhibitory
      regulation of lipolysis (human, hamster, rabbit); (ii) slightly different in
      nature from the receptors of these species since they had weaker affinity for
      clonidine and yohimbine; and however (iii) not of the typical alpha 2-B subtype
      since the affinity of prazosin was lower than that of oxymetazoline in displacing
      [3H]RX 821002 or [3H]yohimbine binding.

PMID- 1974424
TI  - N-terminal degradation of low molecular weight opioid peptides in human
      cerebrospinal fluid.
AB  - Opioid peptides are present in human cerebrospinal fluid (CSF), and their levels
      are reported to change in some pathologic conditions. However, less is known
      about their degradation in CSF. In the present study, human CSF was found to
      contain aminopeptidase activity which hydrolyzed alanyl-, leucyl- and arginyl
      naphthylamides in a ratio of 100:28:27. Twelve CSF samples hydrolyzed alanyl-2
      naphthylamide and degraded Met5-enkephalin (N-terminal hydrolysis) at rates of
      188 +/- 38 and 420 +/- 79 pmol/min/mL respectively. Further, the distribution of
      alanyl-naphthylamidase activity in individual samples (39-437 pmol/min/mL) was
      closely correlated with that of Met5-enkephalin degradation (37-833 pmol/min/mL).
      Both alanyl-naphthylamidase and enkephalin degradation were optimal at pH 7.0 to
      7.5 and were inhibited by aminopeptidase inhibitors amastatin (IC50 = 20 nM),
      bestatin (4-7 microM) and puromycin (30-35 microM). Conversely, degradation was
      unaffected by inhibitors of neutral endopeptidase (phosphoramidon),
      carboxypeptidase N (MERGETPA) or angiotensin converting enzyme (captopril). The
      Km of Met5-enkephalin for the CSF aminopeptidase activity was 201 +/- 19 microM
      (N = 4). Rates of hydrolysis of the Tyr1-Gly2 bond of larger opioid peptides
      decreased with increasing peptide length. Pooled, concentrated CSF hydrolyzed
      Leu5-enkephalin, dynorphin A fragments [1-7], [1-10] and [1-13] and dynorphin A
      at rates of 2.05 +/- 0.27, 1.27 +/- 0.18, 0.94 +/- 0.06, 0.55 +/- 0.14 and 0.16
      +/- 0.03 nmol/min/mL respectively. When analyzed by rocket-immunoelectrophoresis
      against antisera to aminopeptidase M (EC 3.4.11.2), the concentrated CSF formed
      an immunoprecipitate which could be stained histochemically for alanyl
      naphthylamidase activity. These data are consistent with a significant role for
      aminopeptidase M activity in the degradation of low molecular weight opioid
      peptides in human CSF.

PMID- 1974426
TI  - [The N-methyl-D-aspartate receptor complex. Various sites of regulation and
      clinical consequences].
AB  - Amino acids such as L-glutamate und L-aspartate are major excitatory
      neurotransmitters in the mammalian central nervous system (CNS) and potential
      neurotoxins (excitotoxins), which can destroy central neurons by excessive
      activation of respective receptors. In the last three decades evidence has
      accumulated that excitatory amino acids (EAA) are involved in many neurological
      diseases and that pharmacological intervention offers prospects of novel and more
      effective therapies. Three different receptor types for EAA have been identified,
      each being named by the selective agonist to which it is preferentially
      sensitive, i.e. N-methyl-D-aspartate- (NMDA), kainate- and quisqualate-receptors.
      In this review interest is focused primarily on the NMDA-receptor, whose
      structure has been subject of numerous electrophysiological and biochemical
      studies. Today, it is well established that the NMDA-receptor-ionophore complex
      has an agonist binding site for glutamate, NMDA and related EAAs which is coupled
      with an ion channel permeable to Na+, K+, Cl- and Ca2+. Four other binding sites
      for glycine, phencyclidine, Mg2+ and Zn2+ have been identified which can
      differentially modulate the function of the NMDA receptor. An additional
      polyamine binding site has recently been reported. Numerous studies on
      experimental animals demonstrate that modulators of NMDA-mediated
      neurotransmission may have antiepileptic, anxiolytic, muscle-relaxant and memory
      enhancing effects. Particular interest has gained the possible neuroprotective
      efficacy of NMDA-receptor antagonists in neurological diseases such as
      hypoxia/ischemia, hypoglycemia, epilepsy and chronic neurodegenerative disorders
      (Huntington's, Alzheimer's and Parkinson's disease, amyotrophic lateral
      sclerosis, and AIDS encephalopathy).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1974425
TI  - Uptake of peptides containing Tyr-Pro by human and mouse erythrocytes.
AB  - Red blood cells (RBCs) harvested from mice were used to investigate the possible
      existence of an uptake system for peptides in these cells. The radioactively
      iodinated tetrapeptide Tyr-MIF-1 (Tyr-Pro-Leu-Gly-amide) was incubated with RBCs
      for varying lengths of time with or without inhibitors. The RBCs showed saturable
      uptake that could be inhibited by Tyr-Pro containing peptides. Uptake was also
      found in human RBCs, but was more robust in the mouse. Uptake by mouse RBCs was
      temperature dependent and magnesium sensitive but did not require sodium,
      potassium, or glucose. With the exception of some enkephalin- and dynorphin
      related peptides that partially inhibited uptake, most substances tested were
      without effect. The results of HPLC showed internalization of the N-Tyr-Pro
      containing peptides, with accumulation of degradation products over time. The
      degradation products, however, did not inhibit transport, suggesting that
      peptides were transported intact into the RBCs with degradation occurring after
      internalization. This suggestion was strengthened by the finding that only the
      cytosol of the RBC, not its membranes, rapidly degraded Tyr-MIF-1 to free iodine
      and iodotyrosine. Nevertheless, the cytosol contained a large amount of
      immunoreactive material that eluted at the position of intact Tyr-MIF-1 on HPLC.
      These findings show that RBCs can take up, store, and degrade Tyr-Pro containing
      peptides.

PMID- 1974427
TI  - Pharmacokinetics of the anxiolytic beta-carboline derivative abecarnil in the
      mouse, rat, rabbit, dog, cynomolgus monkey and baboon. Studies on species
      differences.
AB  - The pharmacokinetics of abecarnil (isopropyl 6-(benzyloxy)-4-(methoxymethyl)-9H
      pyrido [3,4-b] indole-3-carboxylate, ZK 112 119) were studied in the mouse, rat,
      rabbit, dog, cynomolgus monkey and baboon using 14C-labeled drug and HPLC with
      fluorescence detection for measurement of unchanged drug. Abecarnil was rapidly
      and completely absorbed after oral doses of 10 mg/kg. At higher doses, absorption
      was prolonged and incomplete in the cynomolgus monkey. The bioavailability of
      abecarnil was 20-30% in all the species investigated. The terminal half-life of
      the unchanged drug in plasma was relatively similar in all species (0.6-1.7 h).
      Abecarnil was able to pass the blood-brain barrier achieving concentrations in
      the brain similar to those in plasma. Tissue distribution of labeled compounds
      was rapid with highest concentrations in the liver, adrenals, kidneys and
      pancreas followed by the bone marrow, lungs, heart, fat, spleen, ovaries and
      thyroid gland. Excretion of radiolabeled compounds proceeded predominantly in the
      feces of the rat, the rabbit and the cynomolgus monkey.

PMID- 1974428
TI  - Pharmacokinetics and acute toleration of the beta-carboline derivative abecarnil
      in man.
AB  - Plasma levels of the beta-carboline, abecarnil (isopropyl 6-(benzyloxy)-4
      (methoxymethyl)-9H-pyrido [3,4-b]indole-3- carboxylate, ZK112119) which is
      presently under development as an anxiolytic, were measured by HPLC with
      fluorescence detection in six healthy male volunteers given 30 micrograms/kg i.v.
      and 5 and 10 mg p.o. Following i.v. injection, plasma levels declined
      biphasically with half-lives of 6 min and 3.4 h. The total clearance was 13
      ml/min/kg. After oral administration, maximum concentrations were reached after 2
      h. The bioavailability was approximately 60%. The terminal half-life after p.o.
      administration was 7 h. No clinically relevant changes in ECG, vital signs or
      standard laboratory measurements occurred. Eight different adverse reactions were
      noted by the subjects. The most frequently reported side-effects were tiredness,
      dizziness, unsteady gait and lack of concentration.

PMID- 1974429
TI  - Effect of flutoprazepam on skills essential for driving motor vehicles.
AB  - The effects of the 1,4-benzodiazepine derivative flutoprazepam on the skills
      essential for driving motor vehicles were tested 2.5 h after intake of 1 x 2 mg
      and 1 x 4 mg, comparing with placebo. 18 healthy subjects who had homogeneous
      results in psychological/physical tests took part in the study. The study had a
      double-blind, randomized crossover design with 7-day washout periods. 2.5 h after
      intake of 4 mg flutoprazepam, the ability to drive was impaired. Only a very
      slight reduction in skill was found at the same time under the influence of 2 mg
      of the drug.

PMID- 1974430
TI  - Physico-chemical properties and stability of trans-5-chloro-2-methyl-2,3,3a,12b
      tetrahydro-1H- dibenz[2,3:6,7]oxepino[4,5-c]pyrrolidine maleate.
AB  - The physico-chemical properties of trans-5-chloro-2-methyl-2,3,3a,12b-tetrahydro
      1H- dibenz[2,3:6,7]oxepino[4,5-c]pyrrolidine maleate (Org 5222), a new potential
      antipsychotic compound, were studied by interpretation of its spectra
      (UV,IR,NMR,mass), X-ray analysis, thermal properties, solubilities and partition
      coefficient. Analytical methods such as GLC and TLC were developed for use in
      stability tests. Crystalline Org 5222 was shown to be stable with respect to
      heat. Only excessive exposure to light was shown to induce degradation of
      crystalline Org 5222. In solutions of pH 1, 4 and 7 only slight degradation was
      observed at high temperature or after exposure to light.

PMID- 1974431
TI  - Biotransformation of trans-5-chloro-2-methyl-2,3,3a,12b-tetrahydro-1-H
      dibenz[2,3:6,7]oxepin o [4,5-c]pyrrolidine maleate in rats.
AB  - The metabolism of trans-5-chloro-2-methyl-2,3,3a,12b-tetrahydro-1 H
      dibenz[2,3:6,7]oxepinol [4,5-c]pyrrolidine maleate (Org 5222) labelled with [3H]
      or [14C] was investigated in Wistar rats. Metabolites were identified by mass
      spectrometry, 13C- and 1H-NMR analysis, IR spectroscopy and, wherever possible,
      by comparison with authentic reference compounds. The metabolites found in
      plasma, bile, faeces and urine revealed the processes of metabolism in which Org
      5222 underwent oxidation to yield an N-oxide existing in two diastereoisomeric
      forms, or N-demethylation to yield a demethyl metabolite. A novel metabolite was
      found in bile, viz. a carbamate glucuronide, formed from an intermediate carbamic
      acid, derived from the addition of CO2 to the demethyl metabolite.

PMID- 1974432
TI  - Behavioural pharmacology of trans-5-chloro-2-methyl-2,3,3a,12b-tetrahydro- 1H
      dibenz[2,3:6,7]oxepino-[4,5-c]pyrrolidine maleate, a compound interacting with
      dopaminergic and serotonergic receptors.
AB  - trans-5-Chloro-2-methyl-2,3,3a,12b-tetrahydro-1H- dibenz[2,3:6,7]oxepinol[4,5
      c]pyrrolidine maleate (Org 5222) is a new compound with effects on animal
      behaviour indicating strong antipsychotic potential based on antagonism of
      dopaminergic and serotonergic effects. The compound inhibits apomorphine-induced
      climbing behaviour, mouse locomotor activity, rat activity in an open field,
      shuttle box behaviour in rats, pergolide induced circling in 6-hydroxydopamine(6
      OHDA) lesioned rats, serotonin agonist-induced forepaw treading, head shakes and
      penile erections. The compound is less effective in inducing catalepsy, and
      antagonising SKF-38393 (tetrahydro- 1-phenyl-1H-3-benzazepine-7,8-diol HCl)
      induced circling in 6-OHDA-lesioned rats and it does not induce perioral
      movements in rats. Based on these data and the neurochemical profile of the
      compound it was decided that this compound merits clinical investigation in a
      programme aiming for an effective antipsychotic agent with reduced risks of
      extrapyramidal side-effects.

PMID- 1974434
TI  - China's quest for management of academic medicine.
AB  - The China Medical Board organized a management conference for the presidents of
      China's national medical universities. A three-person consulting team arranged by
      the Association of American Medical Colleges led the conference. Designed as a
      preliminary examination of the management problems faced by the national medical
      universities, the conference covered content similar to that of the AAMC
      Executive Development Seminars, including governance, financial management,
      faculty practice plans, technology transfer, information management, and
      organizational diagnosis. China's national medical universities are strategically
      managed by the Ministry of Public Health in Beijing, and for several years the
      ministry has increasingly decentralized the management and operational planning
      and control of these universities. The universities do not have enough properly
      trained personnel to absorb the additional management responsibilities, and the
      university presidents feel that they and their senior staffs need extensive
      training in adapting western-style management principles and practice to the
      Chinese setting.

PMID- 1974433
TI  - Neurochemical studies with the potential antipsychotic compound trans-5-Chloro-2
      methyl-2,3,3a,12b-tetrahydro-1H- dibenz[2,3:6,7]oxepino[4,5-c]pyrrolidine
      maleate.
AB  - trans-5-Chloro-2-methyl-2,3,3a,12b-tetrahydro-1H-dibenz [2,3:6,7]oxepino[4,5
      c]pyrrolidine maleate (Org 5222) has dopamine D2 antagonistic and negligible
      anticholinergic properties of the classical neuroleptic haloperidol. In addition
      it combines the strong antiserotonergic and antihistaminergic properties of
      chlorpromazine and clozapine with the potent dopamine D-1 antagonistic properties
      of Sch 23390 (R-(+)-delta-chloro-2,3,4,5-tetrahydro-3-methyl-5- phenyl-1H-3
      benazepin-7-ol(Z)-2-buteneoate). This in conjunction to its behavioural
      properties, warrants clinical testing in psychotic patients.

PMID- 1974435
TI  - Synthesis and pharmacological evaluation of 6,8-diaryl 1,2,4-triazolo [4,3,-b]
      and 1,2,3,4,-tetrazolo [1,5-b] pyridazines.
AB  - A series of 6,8-diaryl-1,2,4-triazolo[4,3-b] and 1,2,3,4-tetrazolo[1,5
      b]pyridazines was synthesized from suitable chloropyridazines. The compounds were
      screened in mice for their ability to antagonize maximal electroshock-,
      pentylenetetrazole- and bicuculline-induced seizures; sedative effects were
      evaluated by a study of the spontaneous motor activity. Some of pyridazine
      derivatives exhibited appreciable anticonvulsant activity. Substituting the
      phenyl ring in the 6-position with an halogen atom led to a substantial increase
      of activity. Furthermore, none of the compounds was notably active in tests
      predictive of anxiolytic activity.

PMID- 1974436
TI  - Foot spas as a cause of burns.
AB  - Within 2 weeks the authors saw two patients with deep burns of their feet caused
      by foot spas. Both devices had been used according to the manufacturers'
      instructions and had been approved by The Danish Electric Material Control.
      Examination however showed that the bottom plate of these devices reached
      unacceptably high temperatures that far exceeded the stipulation for approval. As
      a consequence of this report, the rules for approval of foot spas in Denmark have
      been changed, as well as a warning to persons at risk that should be included in
      the directions for use in the future.

PMID- 1974437
TI  - The peripheral dopaminergic system. Basic and clinical advances.

PMID- 1974438
TI  - Effect of dopamine on renal blood flow, prostaglandins, renin and electrolyte
      excretion in normal and hypertensive humans.
AB  - A low dose of dopamine (1 microgram/min/kg) infused for 3 h, which is without
      systemic hemodynamic effects in normal subjects, increased the renal blood flow
      and renal production of prostacyclin (PGI2). This action was blocked by
      metoclopramide as well as by either of two cyclooxygenase (CO) blockers, but
      effects were not altered by administration of the alpha 1 blocker prazosin. Much
      of the effect of dopamine (DA) is apparently via the DA1 receptor, since
      fenoldopam (0.1 microgram/min/kg) reproduced these actions. However, although
      fenoldopam increased glomerular filtration rate and urinary Na+, CO blockers were
      without effect. In contrast neither DA or fenoldopam infusions changed either
      renal blood flow or PGI2 in a group of patients with essential hypertension.
      Renin secretion was shown to be increased via DA1 receptor activation both in
      humans and rat renal tissue. The DA2 receptor may also play a role since
      domperidone can reduce renal blood flow.

PMID- 1974439
TI  - The pharmacology of fenoldopam.
AB  - Fenoldopam is a selective dopamine1 (DA1) receptor agonist. Most of the DA1
      receptor agonist activity of fenoldopam resides in the R-enantiomer, which also
      shows weaker alpha 2-adrenoceptor antagonist activity Fenoldopam produces
      vasodilation in vascular beds that are rich in vascular DA1 receptors, eg, renal
      and mesenteric receptors, and produces an increase in renal blood flow at doses
      that do not affect blood pressure. At higher doses, fenoldopam lowers blood
      pressure but still maintains renal perfusion. In addition to its renal
      vasodilator activity, fenoldopam is natriuretic, possibly resulting from a direct
      effect of DA1 receptors on the proximal convoluted tubule. In animals with
      spontaneous or drug-induced renal failure, fenoldopam improves renal function.

PMID- 1974440
TI  - Clinical experience with intravenous fenoldopam.
AB  - Fenoldopam (Corlopam), a new dopaminergic agent in clinical development by
      SmithKline Beecham Pharmaceuticals, is a dopamine-1 (DA1) agonist at post
      synaptic dopamine receptors. Preclinical and clinical studies have demonstrated
      that it is a potent renal vasodilator as well as a peripheral vasodilator. In
      both normal volunteers and hypertensive patients intravenous fenoldopam causes
      dose-related decreases in blood pressure and important increases in renal
      hemodynamics and function including increased renal blood flow, diuresis and
      natriuresis. Fenoldopam does not alter glomerular filtration. Intravenous
      fenoldopam has been demonstrated to be efficacious in severe hypertensive
      patients in several multicenter, multinational trials. In severe hypertension
      efficacy trials fenoldopam was judged to be as effective as sodium nitroprusside
      and to produce less serious side effects. In patients with moderate to severe
      heart failure, fenoldopam has been demonstrated to produce dose-related acute
      increases in cardiac output, stroke volume and work index, decreased systemic
      vascular resistance but no important changes in pulmonary wedge pressure or right
      atrial pressure. In CHF patients fenoldopam has been demonstrated to be as
      efficacious as sodium nitroprusside. Fenoldopam, as a specific (DA1) agonist
      resulting in decreased peripheral and renal vascular resistance, diuresis,
      natriuresis and increases in cardiac hemodynamics on intravenous administration,
      appears to be an efficacious agent which offers a reasonable alternative in the
      treatment of severe hypertension and acute congestive heart failure.

PMID- 1974441
TI  - Comparison of the central and renal dopamine-1 receptor.
AB  - The dopamine D-1 receptor from striatal membranes was compared with the dopamine
      DA-1 receptor from renal proximal tubules. The dopamine-1 receptors were
      solubilized with 1% sodium cholate and phospholipids after pretreatment with the
      dopamine-1 agonist, SKF R-38393. The soluble receptors were reconstituted into
      phospholipid vesicles after removal of sodium cholate. The receptors were studied
      by radioligand binding using the dopamine-1 antagonist [125I]-SCH 23982. The
      reconstituted dopamine D-1 and DA-1 receptor densities were similar. However, the
      affinity of the solubilized D-1 receptor was 17-fold greater than the solubilized
      DA-1 receptor. The affinity of membrane bound D-1 receptor to the radioligand was
      also greater than that noted for membrane bound DA-1 receptor. The mechanism for
      this difference remains to be determined.

PMID- 1974442
TI  - Identification of dopaminergic nerves in humans.
AB  - It has been well-documented in animal studies that axons of dopaminergic neurons
      can be distinguished from those of noradrenergic neurons by their content of DOPA
      decarboxylase (DDC). We now have evidence that DDC immunoreactivity is also
      specific for dopaminergic axons in the sympathetic nervous system of man. Thus,
      light microscope immunocytochemistry can be used to screen human tissues for
      potential dopaminergic inputs, preparatory to functional analysis. Application of
      this technique has so confirmed the innervation by dopaminergic neurons of human
      kidney and hepatic vasculature. Although similar nerves are found in kidney and
      liver of dog, the specific target structures supplied, and therefore the specific
      functional effects of nerve activation, are different.

PMID- 1974444
TI  - Dopamine-1 and dopamine-2 mechanisms in the control of renal function.
AB  - Dopamine (DA), a catecholamine produced in the kidney, is a renal vasodilator and
      natriuretic substance, but its action at dopamine-1 (DA-1), dopamine-2 (DA-2) and
      alpha- and beta-adrenergic receptors limits its effectiveness as a heuristic tool
      and pharmacologic agent. We have studied the effects of highly selective DA-1 and
      DA-2 receptor agonists and antagonists in normal human subjects and experimental
      animals to determine the precise physiological role of renal dopamine at DA-1 and
      DA-2 receptors within the kidney. We studied fenoldopam, a selective DA-1
      agonist, in normal human subjects in metabolic balances at high (300 mEq/day) and
      low (10 mEq/day) sodium (Na) intake. Selective DA-1 receptor stimulation during
      high Na intake resulted in renal vasodilation, natriuresis and diuresis in a
      sustained manner for 3 hours. The natriuresis was mediated by a reduction in Na
      reabsorption at both proximal and distal tubular sites. In contrast, during low
      Na intake, DA-1 receptor stimulation did not engender a natriuretic or diuretic
      response. Thus, sodium depletion may inhibit the function of renal tubular cells
      in response to DA-1 stimulation. DA-1 receptors are present in the medial layer
      of the renal vasculature, proximal tubule and cortical collecting duct; DA-2
      receptors are localized to the glomerulus, the renal nerves surrounding renal
      blood vessels and possibly the renal vascular endothelium. We have performed
      studies in conscious dogs with indwelling renal arterial catheters to identify
      the physiological role of renal DA to DA-1 and DA-2 receptors.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1974443
TI  - The signal transducer for the dopamine-1 regulated sodium transport in renal
      cortical brush border membrane vesicles.
AB  - We have reported the presence of dopamine-1 (DA-1) and dopamine-2 (DA-2)
      receptors in renal brush border and basolateral membranes. DA-1 agonists
      stimulate adenylate cyclase (AC) and phospholipase C (PLC) activity in both
      membranes. Moreover, the ability of a DA-1 agonist (fenoldopam) to stimulate PLC
      activity is independent of AC activity. A DA-2 agonist (LY171555) by itself was
      without effect and did not enhance the ability of the DA-1 agonist to stimulate
      PLC activity. The DA-1 but not DA-2 agonists inhibit Na+/H+ exchange activity in
      brush border membrane vesicles (BBMV) and Na+/K(+)-ATPase activity in basolateral
      membranes. However, cAMP inhibits, while protein kinase C (presumably via PLC
      activity) stimulates, Na+/H+ exchange activity. We therefore determined the
      effect of DA-1 agonists on Na+/H+ exchange activity when PLC or AC activity was
      blocked using neomycin or dideoxyadenosine, respectively. The drugs were
      incubated with minced renal cortex prior to preparation of BBMV by differential
      centrifugation and MnCl2 precipitation. Enrichment of BBMV was not affected by
      drug treatment. The Na+/H+ exchange activity was assessed by measuring amiloride
      (1 mmol/L) sensitive 22Na+ uptake in BBMV (pHi = 5.5, pHo = 7.5, Nai+ = O, Nao+ =
      1 mmol/L). Neomycin inhibited DA and DA-1-stimulated PLC activity in BBMV in a
      concentration dependent manner (10(-6) to 10(-4) mol/L). Neomycin (10(-4) mol/L)
      completely blocked the ability of DA and DA-1 agonist to stimulate PLC activity
      but had no consistent effect on DA-1 inhibited Na+/H+ exchange activity.
      Dideoxyadenosine inhibited DA and DA-1 simulated AC activity without affecting DA
      1 stimulated PLC activity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1974445
TI  - Dopamine in chronic renal failure.
AB  - In patients with renal disease a reduced renal vasodilatory but conserved
      natriuretic response to dopamine is observed. An inverse relationship exists
      between baseline renal function and the dopamine-induced changes in effective
      renal plasma flow and glomerular filtration rate over a wide range of dopamine
      doses. The renal hemodynamic response to dopamine is also impaired in kidney
      donors. In studies with dopamine antagonists and in measurements of urinary free
      dopamine excretion no evidence was found for increased endogenous renal dopamine
      generation in these patients. The response of effective renal plasma flow and
      filtration fraction to fenoldopam was also impaired. However, the fractional
      sodium excretion in patients with renal disease was not impaired in both short
      term and long-term studies. Perhaps this conserved natriuretic effect is of
      clinical value in these patients.

PMID- 1974446
TI  - Renal dopamine and sodium excretion.
AB  - In the present study, we examined the renal effects of a low dose of fenoldopam
      in pentobarbital anesthetized rats in an attempt to unmask a direct tubular DA-1
      receptor mediated diuresis and natriuresis. We also performed experiments to
      determine the possible contribution of renal dopamine (DA) and DA receptors in
      the natriuretic response to acute sodium loading. Fenoldopam (0.5
      microgram/kg/min) produced significant increases in urine output (UV) and urinary
      sodium excretion (UNaV) without altering mean blood pressure (MBP), renal blood
      flow (RBF) or heart rate (HR), suggesting a direct tubular site of action. This
      renal response to fenoldopam was completely abolished in the presence of the
      selective DA-1 receptor antagonist, SCH 23390. Isotonic NaCl loading (5% body
      weight for 1 h) enhanced urinary DA excretion (UDA V) which correlated
      significantly with the increase in UNa V. Pretreatment with selective DA-1
      receptor antagonist SCH 23390 resulted in significant attenuation of the increase
      in UNa V whereas the increase in UDA V was unaltered. Pretreatment with selective
      DA-2 receptor antagonist domperidone did not alter the increase in UNa V during
      isotonic NaCl loading. These results suggest that renal tubules are endowed with
      DA-1 receptors activation which results in diuresis and natriuresis. Furthermore,
      activation of these DA-1 receptors but not DA-2 receptors by endogenous DA
      contributes to the natriuretic response to isotonic saline loading.

PMID- 1974447
TI  - A renal dopamine-1 receptor defect in two genetic models of hypertension.
AB  - Dopamine (DA), via DA-1 receptors, regulates Na+ transport in the kidneys.
      Dopamine is synthesized from L-DOPA in the proximal tubule and presumably
      secreted as an autocrine/paracrine substance to stimulate DA-1 receptors
      localized on proximal tubular cells. We have previously reported the presence of
      DA-1 receptors in renal cortical homogenates and on the isolated proximal tubule
      of the rat and rabbit, consistent with the dopamine autocrine/paracrine model. We
      have localized DA-1 receptors in the proximal straight tubule of the rabbit, and
      in the cortical collecting duct of the rabbit and rat, but not in the distal
      collecting tubule or the cortical thick ascending loop of Henle. The presence of
      functional DA-1 receptors has been substantiated by the coexistence of DA-1
      agonist-stimulated adenylate cyclase activity in the same nephron segments in
      which DA-r receptors have been found. Increased concentrations of intrarenal
      dopamine induced by dopamine-beta-hydroxylase inhibition with SKF-102698 caused a
      down regulation of proximal tubular DA-1 receptors and almost complete ablation
      of DA-1 agonist stimulated adenylate cyclase activity. Thus, dopamine may play a
      role in the regulation of DA-1 receptors and their linkage with adenylate
      cyclase. Since alterations in the renal dopaminergic system have been measured in
      some forms of experimental hypertension, we studied DA-1 receptors and their
      coupling to adenylate cyclase in the spontaneously hypertensive rat
      (SHR).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1974448
TI  - A single dose of the MHC-linked susceptibility determinant associated with the
      RT1u haplotype is permissive for insulin-dependent diabetes mellitus in the BB
      rat.
AB  - Syndromes of insulin-dependent diabetes mellitus (IDDM) have been described in
      the mouse, in the rat and in man. In all three species, the presence of one or
      more specific alleles of the major histocompatibility complex is a prerequisite
      for the appearance of the disease. In the BB rat, diabetes is associated with the
      RT1u haplotype. We have performed a series of intercrosses of diabetic BB rats
      with normal Lewis and Buffalo rats and examined the offspring of all litters
      producing at least one diabetic animal. Forty-five of the 250 rats that developed
      diabetes were heterozygous for the RT1u haplotype by serotyping. Furthermore, the
      diabetic rats heterozygous by serotyping at the RT1A class I loci were also
      heterozygous at the RT1B and RT1D loci of the class II region and did not show
      evidence of a recombinant haplotype when examined by Southern blot analyses using
      molecular probes for class I and class II genes. Diabetic rats heterozygous or
      homozygous for RT1u were phenotypically indistinguishable with respect to age of
      onset and severity of disease. Therefore, in the rat, as in the human, a single
      dose of the high-risk allele at the major histocompatibility complex is
      sufficient for the development of IDDM if other susceptibility factors and the
      appropriate environmental factors are in place.

PMID- 1974450
TI  - Nonisotopic labelling of a variable number of tandem repeat probe by nick
      translation with biotinylated nucleotides.

PMID- 1974449
TI  - Molecular analysis of the IGHA and MHC class III region genes in one family with
      IgA and C4 deficiencies.
AB  - We report molecular studies in 2 IgA-deficient persons. One of them had an
      unusual association with an acute lymphoblastic leukaemia; his sister was also
      IgA deficient and shared an HLA haplotype and a complotype known to be associated
      to IgA deficiencies. The 2 IgA-deficient siblings also had low C4 serum levels
      due to C4A*Q0 allele. We showed that both defects were transmitted independently
      in the family. Molecular analysis revealed no major structural defects of the
      IGHA coding and switch regions, whereas a broad C4A-21-OHA deletion was
      responsible for the C4A*Q0 phenotype. These results confirm previous data showing
      that IgA deficiencies seem to be, in most cases, a regulatory defect rather than
      a structural defect of the coding IGHA region itself. These data were further
      supported by another molecular study in a patient with a recurrent Landry
      Guillain-Barre syndrome who showed total absence of serum IgA and sIgA+B cells
      with no major structural defect of the IGHA region.

PMID- 1974451
TI  - Gamma-glutamyl transpeptidase in synovial fluid, serum, and urine of patients
      with rheumatoid arthritis.
AB  - The changes in the levels of GGT activity in various body fluids, ESR, SF-protein
      concentration, and SF-WBC count were determined in 59 RA patients and 18 control
      subjects. The SF-GGT and UGGT were markedly elevated in all RA patients
      investigated. The increase of SF-GGT is more pronounced than UGGT. The
      observation of comparable levels of SGGT in RA patients and control subjects
      indicates that SGGT does not gain entry into synovial fluid or urine. No
      differences were noticed in SF-protein concentration whereas ESR levels and SF
      WBC counts were significantly higher in RA patients than in control subjects.
      Statistically significant correlations were observed between SF-GGT versus UGGT,
      SF-WBC, and ESR in females, and between SF-GGT and SF-protein and SGGT in male RA
      patients. The correlation coefficient values between UGGT versus SF-protein, SF
      WBC, and ESR were found to be significant in male RA patients. UGGT levels
      correlated strongly with SGGT in all RA patients. These findings suggest that the
      measurement of SF-GGT and UGGT might be useful in understanding the pathogenesis
      of rheumatoid arthritis.

PMID- 1974452
TI  - Presence of dipeptidyl peptidase II, dipeptidyl peptidase IV, and prolyl
      endopeptidase in effusion from patients with serous otitis media.
AB  - We have measured for the first time, using specific substrates and specific
      fluorometric analyses, activities of three pathophysiologically important
      peptidases, i.e., dipeptidyl peptidase II, dipeptidyl peptidase IV, and prolyl
      endopeptidase in effusions from 45 patients with chronic otitis media with
      effusion. In 20 patients, DPP II and DPP IV were assayed simultaneously in
      effusions and sera. Activity of PEP was also estimated in effusions and sera from
      25 patients. The mean values (+/- SD) of DPP II and DPP IV (n = 45) and PEP (n =
      25) in effusion from patients with OME were 0.020 +/- 0.007, 0.66 +/- 0.04, and
      0.040 +/- 0.006 nmole/min/mg protein, and 0.21 +/- 0.01, 16.2 +/- 1.87, and 1.90
      +/- 0.23 nmole/min/ml of effusion, respectively. The mean values (+/- SD) for DPP
      II, DPP IV, and PEP in sera were 2.82 +/- 0.18, 54.8 +/- 1.23, and 3.73 +/- 0.33
      nmole/min/ml of serum, respectively, which were similar to our previously
      reported values. Activities of DPP II, DPP IV, and PEP of serous effusions were
      comparable to those in serum. However, there was no significant correlation
      between their activities in serum and effusion. This may suggest that the major
      source of these enzymes in effusions may not be serum but the cells in the middle
      ear.

PMID- 1974453
TI  - Extradural somatostatin.

PMID- 1974454
TI  - Narcotics via the epidural route.

PMID- 1974455
TI  - Pain control: narcotics via the epidural route--Part two.

PMID- 1974456
TI  - Blood lead concentration, renal function, and blood pressure in London civil
      servants.
AB  - Blood lead concentration was measured in 398 male and 133 female London civil
      servants not subject to industrial exposure to heavy metals. The relation between
      blood lead and serum creatinine concentrations and blood pressure were examined.
      Blood lead concentration ranged from 0.20 to 1.70 mumol/l with a geometric mean
      concentrations of 0.58 mumol/l in men and 0.46 mumol/l in women (p less than
      0.001). In women blood lead concentration increased with age (r = +0.27; p =
      0.002). In the two sexes blood lead concentration was positively correlated with
      the number of cigarettes smoked a day (men r = +0.17 and women r = +0.22; p less
      than or equal to 0.01), with the reported number of alcoholic beverages consumed
      a day (men r = +0.34 and women r = 0.23; p less than 0.01), and with serum gamma
      glutamyltranspeptidase (men r = +0.23 and women r = +0.14; for men p less than
      0.01). Blood lead concentration was not correlated with body weight, body mass
      index, and employment grade. In men 14% of the variance of blood lead
      concentration was explained by the significant and independent contributions of
      smoking and alcohol intake and in women 16% by age, smoking, and alcohol
      consumption. In men serum creatinine concentration tended to rise by 0.6 mumol/l
      (95% confidence interval from -0.2 to +1.36 mumol/l) for each 25% increment in
      blood lead concentration. In men and women the correlations between blood lead
      concentration and systolic and diastolic blood did not approach statistical
      significance. In conclusion, in subjects not exposed to heavy metals at work
      gender, age, smoking, and alcohol intake are determinants of blood lead
      concentration. At a low level of exposure, lead accumulation may slightly impair
      renal function, whereas blood pressure does not seem to be importantly
      influenced. Alternatively, a slight impairment of renal function may give rise to
      an increase in blood lead concentration.

PMID- 1974457
TI  - Properties of human liver cytosolic aspartate aminotransferase mRNAs generated by
      alternative polyadenylation site selection.
AB  - Human cytosolic aspartate aminotransferase (cAspAT) cDNA clones have been
      isolated from an adult human liver cDNA library. Among the clones, two cDNAs of
      1550 and 1950 base pairs, respectively, have been characterized. These two cDNAs
      differ only in the lengths of their 3' noncoding regions and by the presence of
      one or two putative polyadenylation signals AATAAA. Northern blot analysis
      revealed two different mRNAs of 2.1 and 1.8 kbp in several human tissues, whereas
      Southern blot analysis suggested the existence of a single gene for the human
      cAspAT. The two mRNA species result from the alternative use of two
      polyadenylation signals. In the liver, the relative ratio of these mRNAs varies
      among different species and, in humans at least, during development. The
      properties of the two mRNAs were compared. The half-lives of the 2.1 and 1.8 kbp
      mRNAs, in the HepG2 cell line, are 8 and 12 h, respectively. The two mRNAs have
      similar and rather short poly(A) tracts of 20-50 nucleotides. Both mRNAs are
      capable of directing the in vitro synthesis of the cAspAT protein. We conclude
      that both the 2.1 and 1.8 kbp cAspAT mRNAs are functional and exhibit similar
      properties.

PMID- 1974458
TI  - Peptide models of dynorphin A(1-17) incorporating minimally homologous
      substitutes for the potential amphiphilic beta strand in residues 7-15.
AB  - Two peptide models of dynorphin A(1-17) have been synthesized. These peptides
      incorporate a minimally homologous substitute sequence for residues 6-17,
      including alternating lysine and valine residues substituting for the potential
      amphiphilic beta-strand structure in positions 7-15. Model 1 retains Pro10 from
      the native sequence, but model 2 does not. Compression isotherms of peptide
      monolayers at the air-water interface and CD spectra of peptide films adsorbed
      from aqueous solution onto siliconized quartz slides were evaluated by comparison
      to those of idealized amphiphilic alpha-helical, beta-sheet, and disordered
      peptides. Dynorphin A(1-17) was mostly disordered, whereas beta-endorphin was
      alpha helical. Dynorphin model 1 had properties similar to those of dynorphin A(1
      17) at these interfaces, but model 2 formed strongly amphiphilic beta sheets. In
      binding assays to mu-, delta-, and kappa-opioid receptors in guinea pig brain
      membranes, model 1 reproduced the high potency and selectivity of dynorphin A(1
      17) for kappa receptors, and model 2 was only 3 times less potent and less
      selective for these receptors. Both peptide models retained the high, kappa
      selective agonist activity of dynorphin A(1-17) in guinea pig ileum assays, and
      like dynorphin A(1-17), model 1 had little activity in the rat vas deferens
      assay. In view of the minimal homology of the modeled dynorphin structures, these
      studies support current models of membrane-catalyzed opioid ligand-receptor
      interactions and suggest a role for the amphiphilic alpha-helical and beta-strand
      structures in beta-endorphin and dynorphin A(1-17), respectively, in this
      process.

PMID- 1974459
TI  - Apolipoprotein J: structure and tissue distribution.
AB  - The primary structure of apolipoprotein J (apoJ) was deduced by the combined
      strategies of protein sequencing and cDNA cloning and sequencing. ApoJ, an
      apolipoprotein associated with discrete subclasses of high-density lipoproteins,
      is encoded by a single gene in both the human and mouse genomes. ApoJ is
      synthesized as a 427 amino acid polypeptide that is posttranslationally cleaved
      at an internal bond between Arg-205 and Ser-206. The subunits of apoJ are
      designated apoJ alpha, corresponding to residues 1-205, and apoJ beta,
      corresponding to resides 206-427. The subunits are associated through disulfide
      bonds. Analysis of the primary structure of apoJ predicts the existence of
      amphiphilic helices, which may account for the association of apoJ with
      lipoproteins, and heparin-binding motifs in both subunits. ApoJ appears to be the
      human analogue of a rat protein present in high concentrations in the testis,
      sulfated glycoprotein 2. ApoJ mRNA (1.9 kb) is expressed in all but one tissue
      examined. The mRNA is present in relatively high levels in brain, ovary, testis,
      and liver, is less abundant in heart, spleen, lung, and breast, and is absent in
      T-lymphocytes. ApoJ is unique among previously characterized human
      apolipoproteins in its structure and tissue distribution.

PMID- 1974460
TI  - Differential release of cellular and scrapie prion proteins from cellular
      membranes by phosphatidylinositol-specific phospholipase C.
AB  - The abnormal isoform of the scrapie prion protein PrPSc is both a host-derived
      protein and a component of the infectious agent causing scrapie. PrPSc and the
      normal cellular isoform PrPC have different physical properties that apparently
      arise from a posttranslational event. Both PrP isoforms are covalently modified
      at the carboxy terminus by a glycoinositol phospholipid. Using preparations of
      dissociated cells derived from normal and scrapie-infected hamster brain tissue,
      we find that the majority of PrPC is released from membranes by
      phosphatidylinositol-specific phospholipase C (PIPLC), while PrPSc is resistant
      to release. In contrast, purified denatured PrP 27-30 (which is formed from PrPSc
      during purification by proteolysis of the amino terminus) is completely cleaved
      by PIPLC. Incubation of the cell preparations with proteinase K cleaves PrPSc to
      form PrP 27-30, demonstrating that PrPSc is accessible to added enzymes. We have
      also developed a protocol involving biotinylation that gives a quantitative
      estimate of the fraction of a protein exposed to the cell exterior. Using this
      strategy, we find that a large portion of PrPSc in the cell preparations reacts
      with a membrane-impermeant biotinylation reagent. Whether alternative membrane
      anchoring of PrPSc, inaccessibility of the glycoinositol phospholipid anchor to
      PIPLC, or binding to another cellular component is responsible for the
      differential release of prion proteins from cells remains to be determined.

PMID- 1974461
TI  - Chaperonin-facilitated refolding of ribulosebisphosphate carboxylase and ATP
      hydrolysis by chaperonin 60 (groEL) are K+ dependent.
AB  - Both the chaperonin- and MgATP-dependent reconstitution of unfolded
      ribulosebisphosphate carboxylase (Rubisco) and the uncoupled ATPase activity of
      chaperonin 60 (groEL) require ionic potassium. The spontaneous, chaperonin
      independent reconstitution of Rubisco, observed at 15 but not at 25 degrees C,
      requires no K+ and is actually inhibited by chaperonin 60, with which the
      unfolded or partly folded Rubisco forms a stable binary complex. The chaperonin
      dependent reconstitution of Rubisco involves the formation of a complex between
      chaperonin 60 and chaperonin 10 (groES). Formation of this complex almost
      completely inhibits the uncoupled ATPase activity of chaperonin 60. Furthermore,
      although the formation of the chaperonin 60-chaperonin 10 complex requires the
      presence of MgATP, hydrolysis of ATP may not be required, since complex formation
      occurs in the absence of K+. The interaction of chaperonin 60 with unfolded or
      partly folded Rubisco does not require MgATP, K+, or chaperonin 10. However,
      discharge of the complex of chaperonin 60-Rubisco, which leads to the formation
      of active Rubisco dimers, requires chaperonin 10 and a coupled, K(+)-dependent
      hydrolysis of ATP. We propose that a role of chaperonin 10 is to couple the K(+)
      dependent hydrolysis of ATP to the release of the folded monomers of the target
      protein from chaperonin 60.

PMID- 1974462
TI  - A site-directed mutagenesis study on Escherichia coli inorganic pyrophosphatase.
      Glutamic acid-98 and lysine-104 are important for structural integrity, whereas
      aspartic acids-97 and -102 are essential for catalytic activity.
AB  - Analysis of the conservation of functional residues between yeast and Escherichia
      coli inorganic pyrophosphatases (PPases) suggested that Asp-97, Glu-98, Asp-102,
      and Lys-104 are important for the action of E. coli PPase [Lahti, R., Kolakowski,
      L. F., Heinonen, J., Vihinen, M., Pohjanoksa, K., & Cooperman, B. S. (1990)
      Biochim. Biophys. Acta 1038, 338-345]. We replaced these four residues by
      oligonucleotide-directed mutagenesis, giving variant PPases DV97, DE97, EV98,
      DV102, DE102, KI104, and KR104. PPase variants DV97, DV102, and KI104 had no
      enzyme activity, whereas PPase variants DE97, EV98, DE102, and KR104 had 22%,
      33%, 3%, and 3% of the wild-type PPase activity, respectively. This suggests that
      Asp-97, Asp-102, and Lys-104 are essential for the catalytic activity of E. coli
      PPase. PPase variants DV98 and KR104 also had an increased sensitivity to heat
      denaturation; incubation of these mutant PPases at 75 degrees C for 15 min in the
      presence of 5 mM magnesium ion decreased the activity to 20% and 1%,
      respectively, of the initial value while 74% of the activity was observed with
      wild-type PPase. Furthermore, these thermolabile mutant PPases displayed the most
      profound conformational changes of the PPase variants examined, as demonstrated
      by the binding of the fluorescent dye Nile red that monitors the hydrophobicity
      of protein surfaces. Accordingly, Glu-98 and Lys-104 seem to be important for the
      structural integrity of E. coli PPase.

PMID- 1974463
TI  - The role of lysine-234 in beta-lactamase catalysis probed by site-directed
      mutagenesis.
AB  - Lys-234 has been postulated to participate in beta-lactamase catalysis by acting
      as an electrostatic anchor for the C3 carboxylate of penicillins [Herzberg, O., &
      Moult, J. (1987) Science 236, 694-701]. To test this hypothesis, site-directed
      mutagenesis was used to convert the Lys-234 in Bacillus licheniformis beta
      lactamase into Glu-234 or Ala-234. The wild-type, Glu-234, and Ala-234 beta
      lactamases have been expressed in Bacillus subtilis and purified to homogeneity.
      The wild-type, K234E, and K234A enzymes have virtually identical circular
      dichroism and fluorescence spectra, similar thermal stabilities at neutral pH,
      and the same susceptibilities to proteolysis, indicating the lack of significant
      structural perturbation caused by the mutation. At acidic and basic pH the mutant
      enzymes have the same native circular dichroism as the wild-type enzyme but the
      thermal stability is significantly different. The mutations cause perturbations
      of the pK values of the ionizing groups responsible for the pH dependence of the
      catalytic reaction in both the free enzyme and the E.S complex. As expected,
      conversion of Lys-234 to Ala or Glu decreased substrate binding (Km) by 1-2
      orders of magnitude for several penicillin and cephalosporin substrates at
      neutral and higher pH. However, at low pH, Km is essentially the same for the
      K234E and K234A enzymes as for the wild-type enzyme. Furthermore, decreases of 2
      3 orders of magnitude in kcat were also observed, indicating substantial effects
      on the transition-state binding, as well as on ground-state binding.
      Surprisingly, changing the C3 carboxylate of phenoxymethylpenicillin to a
      hydroxymethyl group led to little difference in kinetic properties with the K234E
      or K234A enzyme. The results of this investigation indicate the Lys-234 is an
      important active-site residue involved in both ground-state and transition-state
      binding.

PMID- 1974464
TI  - Identification of cellular proteins binding to the scrapie prion protein.
AB  - The scrapie prion protein (PrPSc) is an abnormal isoform of the cellular protein
      PrPc. PrPSc is found only in animals with scrapie or other prion diseases. The
      invariable association of PrPSc with infectivity suggests that PrPSc is a
      component of the infectious particle. In this study, we report the identification
      of two proteins from hamster brain of 45 and 110 kDa (denoted PrP ligands Pli 45
      and Pli 110) which were able to bind to PrP 27-30, the protease-resistant core of
      PrPSc on ligand blots. Pli 45 and Pli 110 also bound PrPC. Both Pli's had
      isoelectric points of approximately 5. The dissociation rate constant of the Pli
      45/PrP 27-30 complex was 3 x 10(-6) s-1. Amino acid and protein sequence analyses
      were performed on purified Pli 45. Both the composition and the sequence were
      almost identical with those predicted for mouse glial fibrillary acidic protein
      (GFAP). Furthermore, antibodies to Pli 45 reacted with recombinant GFAP. The
      identification of proteins which interact with the PrP isoforms in normal and
      diseased brain may provide new insights into the function of PrPC and into the
      molecular mechanisms underlying prion diseases.

PMID- 1974465
TI  - Evaluation of interconversion between (R)- and (S)-enantiomers of beta
      aminoisobutyrate.
AB  - The conversion of (R)- to (S)-beta-aminoisobutyrate was observed in the presence
      of D-3-aminoisobutyrate-pyruvate aminotransferase, aminobutyrate
      aminotransferase, pyruvate and L-glutamate. The reverse reaction was also found
      in the presence of 2-oxoglutarate and L-alanine. Neither D-3-aminoisobutyrate
      pyruvate aminotransferase nor aminobutyrate aminotransferase revealed a racemase
      activity of the enantiomorphs.

PMID- 1974466
TI  - Spatial and temporal distribution of a Drosophila melanogaster embryonic variable
      nuclear antigen.
AB  - A polyclonal antibody has been prepared that specifically recognises a nuclear
      protein antigen in Drosophila embryos. During development, the antigen appears
      initially to be uniformly distributed but by nuclear division cycle 10 is seen to
      accumulate in nuclei in a manner suggesting that it is destroyed or becomes
      modified upon transition from S- to M phase of the nuclear division cycle. This
      conclusion is supported by the observed disappearance of the antigen from the
      postblastoderm nuclei in a manner that reflects the pattern of the first
      asynchronous postblastoderm cell division and persistence in the polyploid nuclei
      of the amnioserosa that do not undergo further cell or nuclear division. In
      Western blot experiments, the antibody detects specifically a 105 kDa nuclear
      protein that probably corresponds to the antigen detected in embryos by
      immunocytochemical means.

PMID- 1974467
TI  - Guanylate cyclase in olfactory cilia from rat and pig.
AB  - A guanylate cyclase was identified in cilia from rat and pig olfactory epithelia.
      Enzyme activities were 200-250 and 90-100 pmol/min.mg-1, respectively. Activity
      required the presence of non-ionic detergents, e.g., 0.1% Lubrol PX. MnGTP, not
      MgGTP was used as a substrate. Furthermore, 0.9 mM free Mn2+ was necessary for
      optimal activity indicating a regulatory site for a divalent cation. The
      guanylate cyclase displayed sigmoidal Michaelis-Menten kinetics suggesting
      cooperativity between MnGTP and enzyme. S0.5 was 160 microM MnGTP. The Hill
      coefficient of 1.7 indicates that more than one class of substrate-binding sites
      interact in a positive cooperative manner. ATP inhibited the enzyme and
      linearized plots of substrate kinetics with MnGTP. SH-Blocking agents reversibly
      inhibited enzyme activity. Sodium azide and nitroprusside were without effect as
      were several odorants. A guanylate cyclase activity in cilia from tracheal tissue
      had properties similar to the olfactory enzyme.

PMID- 1974468
TI  - Effects of calcium on the stability and activity of guinea pig liver
      transglutaminase.
AB  - The binding of calcium to transglutaminase was studied by a kinetic method and by
      spectrophotometric titration. By the first method, we have shown that the binding
      of a single calcium per molecule, with a binding constant of 7500 +/- 1300 M-1
      (at 55 degrees C), was responsible for the enhancement of the thermostability.
      The kinetic constants of the deactivation for the unliganded native form and the
      liganded native one are 1.47 +/- 0.04 min-1 and 0.32 +/- 0.05 min-1 respectively.
      The enhancement of thermostability is due to the stabilization of the native
      form, since the deactivation constants of the liganded and unliganded
      intermediate forms are equal. The total number of calcium binding sites,
      determined by titration is 4, and therefore, only 1 of them should be implicated
      in the thermostability. The 4 apparent association constants have been determined
      by a non-linear fitting of the data to the Adair equation. We have also shown a
      positive co-operative behaviour of the transglutaminase when the transferase is
      monitored versus calcium concentration.

PMID- 1974469
TI  - [The species characteristics of the beta-adrenergic regulation of gastric
      secretion in man and dog].
AB  - In chronic experiment on dogs it has been established that the subcutaneous
      injection of equimolar doses of izadrine (nonselective beta-adrenergic agonist),
      alupent (moderately selective beta 2-adrenergic agonist) and salbutamol
      (predominantly beta 2-adrenergic agonist) suppresses the pentagastric secretion
      approximately in the same degree. The blockade of beta-adrenoreceptors by the
      anapriline intensifies the gastric secretion stimulated by pentagastrin. All
      investigated adrenoactive agents didn't effect the dogs' histamine gastric
      secretion. In healthy men the activation of beta 2-adrenergic receptors by
      alupent accompanied by the expressed intensification of basal, pentagastrin and
      submaximal histamine gastric secretion. The blockade of these receptors by
      anaprilin decreases the gastric secretion. It has been concluded that only beta 2
      adrenoceptors take part in the gastric secretion regulation. Considerable
      specific differences in the reaction of gastric glands on the activation of beta
      adrenoreceptors are revealed: in human beings it leads to the excitation, in dogs
      -to the suppression of secretory cells.

PMID- 1974470
TI  - Histaminergic effects on the isolated rat ovarian artery during the estrous
      cycle.
AB  - Histamine may play a role in many of the events occurring in the ovarian tissue
      and leading to ovulation. To elucidate the histaminergic influence on the ovarian
      vasculature, the mechanical response of the isolated rat ovarian artery to
      histamine and histamine agonists was investigated. Histamine relaxed the
      precontracted vessel segments in a concentration-dependent way, amounting to 82.7
      +/- 4.3% of the papaverine-induced relaxation. This relaxant effect was
      counteracted by both the H1 antagonist, pyrilamine, and the H2 antagonist,
      cimetidine. That the effect of histamine was mediated by both histamine receptor
      subtypes was further confirmed by the relaxant effect produced in the presence of
      either of the H1-specific agonists, 2-pyridylethylamine and 2-methylhistamine on
      the one hand, and the H2-specific agonists, impromidine and 4-methylhistamine on
      the other. The H1 receptor-induced relaxation was mediated via an effect on the
      endothelium, whereas the H2 receptor-mediated relaxation was mostly a direct
      effect on the smooth musculature in the vessel wall. No major differences in the
      mechanical response of the rat ovarian artery were seen during the different
      stages of the estrous cycle, although at late proestrus, just before ovulation,
      the maximum relaxation induced by histamine was particularly high, in spite of a
      low sensitivity of the receptors for the amine.

PMID- 1974471
TI  - Differential expression of CD54/intercellular adhesion molecule-1 in myeloid
      leukemias and in lymphoproliferative disorders.
AB  - Indirect immunofluorescence staining with monoclonal antibody (MoAb) CL203.4 of
      malignant cells from 269 patients with hematologic malignancies showed a
      heterogeneous expression of CD54/intercellular adhesion molecule-1 (ICAM-1). This
      marker was expressed by malignant cells of 57 out of 118 patients with myeloid
      malignancies and 69 out of 135 with B-lymphoid malignancies. On the other hand,
      CD54 was not detected on malignant cells of 16 patients with T-lymphoid
      malignancies. In myeloid malignancies, CD54 is preferentially expressed by "stem
      cell-derived" malignancies, being detectable on blast cells from almost all
      patients affected by chronic myelogenous leukemia in blast phase or
      myelodysplastic syndromes and by only 34% of patients with de novo acute myeloid
      leukemia (AML). The expression of CD54 did not correlate with any specific
      myeloid FAB subtype, although three cases of highly undifferentiated AML (FAB MO)
      displayed maximal levels of the antigen. The expression of CD54 in AML was
      significantly associated with that of CD34 and HLA-DR antigens. In B-lymphoid
      malignancies, CD54 expression appears to correlate with the differentiation stage
      of malignant cells, since B-origin acute lymphoblastic leukemias and conventional
      B-chronic lymphocytic leukemias (B-CLL; ie, "dim SIg" CLL) expressed lower levels
      of CD54 than more mature lymphoproliferative disorders ("bright SIg" CLL,
      prolymphocytic leukemias, and lymphoplasmacytic tumors). "High-grade" B-cell non
      Hodgkin's lymphomas (B-NHL) express in general a higher level of CD54 than "low
      grade" ones. This finding in conjunction with the expression of CD54 in all 17
      patients with "bright SIg" CLL investigated (characterized by marked organomegaly
      and poor prognosis) suggest that the differential expression of CD54 in
      lymphoproliferative disorders may also relate to their degree of malignancy.

PMID- 1974472
TI  - RFLP and deletion analysis for X-linked chronic granulomatous disease using the
      cDNA probe: potential for improved prenatal diagnosis and carrier determination.
AB  - The molecular basis of X-linked chronic granulomatous disease (X-CGD) has
      recently been elucidated and the defective gene identified and isolated. Two
      restriction fragment-length polymorphisms have been identified using the X-CGD
      cDNA probe. We have analyzed eight families with X-CGD and seven normal,
      unrelated females and have demonstrated that these polymorphisms are not in
      linkage disequilibrium. This should increase to approximately 50% the proportion
      of families to whom first-trimester prenatal diagnosis can be offered.
      Unambiguous determination of carrier status in related females in informative
      families will also be possible. In addition, we have identified an apparently
      unique small deletion in the X-CGD gene in a family affected by this disease,
      members of which are not informative for either polymorphism. This will allow
      prenatal diagnosis and carrier determination in this family.

PMID- 1974473
TI  - Antihypertensive and adverse biochemical effects of bendrofluazide.

PMID- 1974474
TI  - Influence of glucagon on protein and leucine metabolism: a study in fasting man
      with induced insulin resistance.
AB  - The counter-regulatory hormones, including glucagon, may be involved in the
      generation of postoperative negative nitrogen balance. We examined the influence
      of glucagon on whole body and forearm muscle protein kinetics, determined by L-[1
      13C, 15N]leucine, in two matched groups of healthy fasting subjects. In one study
      somatostatin alone was infused continuously (0.12 mg h-1) and in another with
      glucagon (0.04 mg h-1) to generate insulin resistance. Somatostatin infusion
      increased leucine oxidation (P less than 0.05) and reduced the negative protein
      balance (P less than 0.01) across the forearm; the 15 per cent decrease in
      protein breakdown was not significant. Whole body leucine kinetics showed
      increased flux (P less than 0.05) and synthesis (P less than 0.01) but reduced
      oxidation (P less than 0.05). Hyperglucagonaemia caused a threefold enhancement
      of leucine oxidation (P less than 0.02), while the negative protein balance
      further increased (P less than 0.05) across the forearm. Whole body leucine flux
      was unchanged; oxidation increased (P less than 0.01) and synthesis decreased (P
      less than 0.01). These studies confirm that physiological hyperglucagonaemia
      during insulin resistance is catabolic in the short-term and indicates, for the
      first time, that glucagon may influence muscle protein metabolism acutely in man.
      We suggest that therapeutic manoeuvres designed to reduce glucagon levels after
      surgery may ameliorate protein kinetic abnormalities.

PMID- 1974475
TI  - Late outcome of undersewing alone for gastric ulcer haemorrhage.
AB  - Between 1977 and 1988 22 patients requiring urgent surgery for bleeding gastric
      ulceration were managed by simple undersewing of the ulcer. Long-term follow-up
      of these patients was undertaken to determine the risk of recurrent gastric
      ulceration and further gastric ulcer haemorrhage. Two patients died in the
      immediate perioperative period leaving 20 patients available for long-term follow
      up (mean 43.3 months). Three recurrent gastric ulcers were diagnosed, two of
      these presenting with haemorrhage. No patient presented with further gastric
      ulceration while on histamine (H2) receptor antagonist therapy. The long-term
      outcome of undersewing alone, when combined with maintenance H2-receptor
      antagonist therapy, is satisfactory in terms of low mortality and low risk of
      ulcer recurrence.

PMID- 1974476
TI  - [The effect of adrenergic beta receptor blockers on phospholipid metabolism in
      mast cells].
AB  - The aim of this study was to determine whether beta adrenergic receptor blocking
      drugs exaprolol, metipranolol and propranolol effect the metabolism of
      phospholipids in isolated rat mast cells. The phospholipids were labelled by 3H
      arachidonic acid (3H-AA) and 32P. Exaprolol, metipranolol and propranolol
      significantly modulated 32P incorporation into phospholipids of resting and 48/80
      stimulated cells. Atenolol had no effect. Studies with 3H-AA Labelled mast cells
      showed an enhanced liberation of arachidonate related radioactivity on exaprolol
      and propranolol treatment. The results indicated that 3H-activity was lost mainly
      from phosphatidylethanolamine. Atenolol and metipranolol significantly decreased
      the 48/80 stimulated 3H-AA release.

PMID- 1974477
TI  - Adenylate cyclase uncoupled beta-adrenergic receptors in salamander proximal
      tubules.
AB  - The isolated perfused proximal tubule of the neotenic salamander Ambystoma
      tigrinum responds with either a hyperpolarization or depolarization of both the
      basolateral cell membrane and transepithelial potentials following the addition
      of 10(-5) M isoproterenol to the bath superfusate. Both responses were blocked by
      10(-6) M propranolol but neither response was mimicked by 10(-4) M cAMP. beta
      Adrenergic binding studies of individual microdissected proximal tubules using (
      )-[3H]CGP-12177 as a hydrophyllic radioligand and (+/-)-timolol (0.1 mM) as the
      displacer drug revealed two distinct populations of proximal tubules possessing
      either low (KD = 153.8 nM; Bmax = 110.2 fM/mm) or high affinity (KD = 12.0 nM:
      Bmax = 3.9 fM/mm) binding characteristics. Competition studies indicated that the
      bound (-)-[3H]CGP-12177 behaved as a typical beta-adrenergic ligand, being
      displaced by (-)-isoproterenol but not by (+)-isoproterenol or (-)-phenylephrine.
      However, neither appeared to be coupled to the adenylate cyclase system. These
      data suggest the presence of functional beta-adrenergic receptors that do not
      appear to be coupled to the adenylate cyclase system.

PMID- 1974478
TI  - Policy protests, scientific spats take centre stage at Sixth International AIDS
      Conference.

PMID- 1974479
TI  - Down-regulation of c-myc and c-Ha-ras gene expression by tiazofurin in rat
      hepatoma cells.
AB  - There was an overexpression of the c-myc gene (11-fold) and of the c-Ha-ras gene
      (2-fold) in rat hepatoma 3924A cells compared to normal rat liver as measured by
      dot-blot analysis of total cytoplasmic RNA. The overexpression of c-myc was
      attributed to a 10- to 14-fold amplification and rearrangement of the c-myc
      sequences as determined by Southern blot analysis. The expression of the c-myc
      also was dependent upon the proliferative state of the hepatoma cells. Tiazofurin
      (2-beta-D-ribofuranosylthiazole-4-carboxamide; NSC 286193), an inhibitor of the
      activity of IMP dehydrogenase (EC 1.1.1.205), the rate-limiting enzyme of GTP
      biosynthesis, resulted in a rapid drop (less than 1 h) to 50% of control in the
      target enzyme activity in the hepatoma cells and in a subsequent marked decrease
      to 55% in GTP concentration. These events were followed at 12 h of tiazofurin
      treatment by a 3-fold reduction in the expression of the c-myc gene and a 9-fold
      decline in that of the c-Ha-ras gene. These results in the hepatoma cells provide
      evidence in support of the earlier demonstrated correlation in K562 cells between
      GTP concentration and expression of c-myc and c-ras genes (Olah et al., 1989).
      These genes might depend on GTP for their expression in hepatoma cells and they
      might cooperate in a signal pathway that controls cell proliferation.

PMID- 1974481
TI  - Carbonic anhydrase and neuronal enzymes in cultured glomus cells of the carotid
      body of the rat.
AB  - The cellular localization of carbonic anhydrase (CAH) in the carotid body of the
      rat was investigated by means of Hansson's cobalt-precipitation technique in
      cultures of dissociated cells. In both young (2-day-old) and old (77-day-old)
      cultures, the parenchymal glomus (type-I) cells were selectively stained by this
      technique, and in addition expressed tyrosine hydroxylase and neuron-specific
      enolase as revealed by immunofluorescence. Enzymic reaction product of CAH
      appeared to be predominantly intracellular since staining was more intense and
      occurred more rapidly following permeabilization of the cell membranes with
      Triton X-100; its formation was inhibited by the CAH-inhibitor acetazolamide (1
      10 microM) or by increasing the pH from 5.8 to 7.5. Cryostat sections of the
      carotid bifurcation revealed intense CAH-reaction product in cell clusters of the
      carotid body, in a few cells of the nodose ganglion, and in red blood cells.
      Neuronal cell bodies of the petrosal ganglion and superior cervical ganglion
      (SCG) were largely non-reactive. The SCG is known to contain clusters of small
      intensely fluorescent (SIF) cells, which were also non-reactive when grown in
      dissociated cell culture. Thus, although glomus and SIF cells are often
      considered to be similar cell types, functional CAH-activity appears unique to
      glomus cells, and this may be important for the physiological response of the
      carotid body to certain chemosensory stimuli.

PMID- 1974480
TI  - Two different types of dynorphin-A-immunoreactive terminals in rat substantia
      nigra.
AB  - The opioid peptide dynorphin A (1-17) is the third transmitter identified in the
      striatonigral projection, the other two being gamma-aminobutyric acid (GABA) and
      substance P. The ultrastructural features of the dynorphinergic terminals in
      substantia nigra/pars reticulata were studied using pre-embedding
      immunocytochemistry with the classical peroxidase-antiperoxidase-diaminobenzidine
      method; these features were compared with GABAergic boutons visualized with an
      immunogold method. Two distinct types of dynorphin-A-immunoreactive boutons could
      be identified: (1) type A (81%) possessing characteristics similar to the
      GABAergic nerve endings in this region, i.e., large pleomorphic vesicles and
      symmetric synaptic contacts; (2) type B (19%) displaying asymmetric synaptic
      zones and small, mostly round vesicles. These results are in agreement with
      physiological studies suggesting a dual action of dynorphin A in substantia
      nigra.

PMID- 1974482
TI  - Human T cell clones with gamma/delta and alpha/beta receptors are differently
      stimulated by monoclonal antibodies to CD2.
AB  - Requirements for stimulating autocrine proliferation of human T cell clones
      expressing either alpha/beta or gamma/delta antigen receptors via the
      "alternative" CD2 pathway have been examined using a large set of monoclonal
      antibodies (mAb). In the presence of autologous accessory cells (AC, B
      lymphoblastoid cell lines) 2 of 13 single CD2 mAb (CLB-T11.1/1 and 6F10.3)
      stimulated proliferation of gamma/delta but not alpha/beta cells. Interleukin
      (IL) 1 or IL 6 did not substitute for AC in stimulating gamma/delta clones.
      Addition of CD28 mAb YTH 913.12 with the CD2 mAb did not result in stimulation of
      any alpha/beta clones. In the absence of AC, none of the CD2 mAb singly could
      stimulate any T cell clones, but pairs of mAb directed to different epitopes of
      CD2 (CLB-T11.1/1 + CLB- T11.2/1 or 6F10.3 + 39C1.5) stimulated both alpha/beta
      and gamma/delta clones. In both cases, stimulation was reduced by the presence of
      CD3 mAb. These results confirm that the established AC-independent alternative
      pathway of T cell activation, which requires binding of two separate epitopes of
      CD2, operates in both gamma/delta and alpha/beta T cells, and further suggest
      that an additional pathway initiated by binding of a single CD2 epitope in the
      presence of AC is exclusively operational in gamma/delta cells.

PMID- 1974483
TI  - Cytofluorometric analysis of lymphocyte subsets in thyroid aspirates from
      patients with autonomously functioning nodules.
AB  - A microscale method, based on two-colour dye immunolabelling and flow sorting
      cytofluorometry, was used to characterize lymphocyte subsets in thyroid tissue
      specimens obtained by fine-needle aspiration (FNA) in 21 patients with
      autonomously functioning thyroid nodule (AFTN) and five patients with cold
      thyroid nodule (CTN). Inversion of the ratio between CD4+ and CD8+ lymphocytes,
      due to a relative increase of CD8+ cells, was found among intrathyroidal
      lymphocytes in AFTN patients. The abnormal lymphocyte subset distribution was not
      observed in the peripheral blood of the same group of patients. In patients with
      CTN the lymphocyte subset distribution was normal, both in the thyroid and in the
      peripheral blood. In AFTN patients, a significant correlation was observed
      between the decrease of intrathyroidal CD4+/CD8+ ratio and the increase of plasma
      thyroid hormone levels. Whether the immunological abnormalities found in AFTN
      could play a pathogenetic role in the clinical presentation and outcome of the
      disease remains to be established. The FNA-applied micromethod used in this study
      could be extended as a routine investigation to characterize the immunogenic
      substrate of thyroid disorders.

PMID- 1974484
TI  - Arginine potentiates the GHRH- but not the pyridostigmine-induced GH secretion in
      normal short children. Further evidence for a somatostatin suppressing effect of
      arginine.
AB  - To investigate the mechanism underlying the GH-releasing effect of arginine
      (ARG), we studied the interactions of ARG (0.5 g/kg infused i.v. over 30 min)
      with GHRH (1 microgram/kg i.v.) and with pyridostigmine (PD, 60 mg orally) on GH
      secretion in 15 children and adolescents with familial short stature (5.1-15.4
      years). In a group of eight subjects ARG induced a GH increase not statistically
      different to that observed after GHRH (peak, mean +/- SEM: 38.0 +/- 10.4 vs 64.0
      +/- 14.4 mU/l). The combined administration of ARG and GHRH led to GH levels (101
      +/- 15.2 mU/l) higher than those observed after GHRH (P less than 0.025) or ARG
      alone (P less than 0.001) and overlapping with those recorded after combined PD
      and GHRH administration (111 +/- 22.4 mU/l). In the other seven subjects, ARG and
      PD administration induced a similar GH response either when administered alone
      (25.2 +/- 13.6 and 27.8 +/- 4.0 mU/l, respectively) or in combination (33.8 +/-
      5.4 mU/l). In conclusion, our results show that in children ARG administration
      potentiates GHRH- but not PD-induced GH increase. These findings agree with the
      hypothesis that the GH-releasing effect of both ARG and PD is mediated via the
      same mechanism, namely, by suppression of endogeneous somatostatin release.
      Combined administration of either ARG or PD with GHRH has a similar striking GH
      releasing effect which is clearly higher than that of GHRH alone.

PMID- 1974485
TI  - Haplotype analysis for CF-linked DNA polymorphisms in Switzerland.
AB  - A total of 295 patients, parents and unaffected sibs from 106 CF-families in
      central and northeastern Switzerland were investigated with probes 7C22(D7S16),
      metH, metD, pKM19, pXV-2c and pJ3.11(D7S8) for eight DNA polymorphisms (RFLP's).
      Linkage disequilibrium to the CF locus and haplotype frequencies were compared to
      those in other populations. They are comparable to other Caucasian populations
      and, for pKM 19 and pXV-2c, very close to the findings in Italy. The prevalence
      of certain haplotypes among the CF and the normal allele-bearing chromosomes
      indicate that the majority of the CF cases are probably the result of one ancient
      mutation in a common ancestor, but that there may be allelic heterogeneity
      accounting for an important proportion of patients, that may differ between
      countries or regions. Informative family constellations for the different
      polymorphisms in Switzerland and strategies for carrier detection and prenatal
      diagnosis are discussed. Haplotype analyses for each country and its ethnic
      subgroups are recommended.

PMID- 1974486
TI  - Rate of recombination of chromosomes 21 in parents of children with Down
      syndrome.
AB  - To test the hypothesis of reduced chiasma frequency causing nondisjunction during
      meiosis, we examined 34 Down syndrome patients and their parents. Chromosomal
      polymorphisms and RFLP markers were used to trace the parental origin as well as
      the frequency of recombination of chromosomes 21. In all but one case, the
      parental origin and the meiotic stage of nondisjunction could be established by
      either technique. In 11 cases recombination could be deduced to have taken place
      during meiosis in the parent who contributed the extra chromosome 21. Because of
      the underestimation which is inherent in the methods used, these results do not
      seem to support the chiasma theory.

PMID- 1974487
TI  - Restriction site polymorphism at the LPA (Lp(a) apolipoprotein; apolipoprotein
      (a)) locus.
AB  - A restriction site polymorphism in the Lp(a) apolipoprotein gene (the LPA gene)
      is reported. The basis for the polymorphism is presence or absence of an MspI
      restriction site that appears to be 3' to the last kringle IV structure of the
      gene. The "1" gene (presence of the restriction site) has a frequency of 0.316
      and the "2" gene (absence of the restriction site) has a frequency of 0.684. Both
      members of each of 67 monozygotic (MZ) twin pairs had the same genotype and there
      was Mendelian segregation of the DNA variants in 40 families with a total of 75
      children. There was a lower proportion of people with genotype 1-1 in the top
      quartile than in the 3 bottom quartiles of the population distribution of Lp(a)
      lipoprotein levels but the difference did not reach statistical significance.

PMID- 1974488
TI  - Isradipine in monotherapy and in combination with bopindolol: results of a 3
      month multicentre study in hypertensives.
AB  - The antihypertensive effect and safety of treatment of hypertension with
      isradipine, a Ca antagonist of dihydropyridine group in monotherapy and in
      combination with the betablocker bopindolol was assessed in a multicentre study
      joined by six Czechoslovak centres. When administered alone to 102 patients with
      essential hypertension stages I and II, isradipine was effective in 59%. Forty
      one per cent of patients required combined therapy. The treatment led to a marked
      decrease in diastolic BP in smokers and non-smokers alike. A significant rise in
      ALP was observed during therapy in both therapeutic regimens. A significant
      decrease in cholesterolaemia was found in patients treated with the isradipine
      bopindolol combination. No serious adverse effects were seen during three-month
      follow-up.

PMID- 1974490
TI  - Peripheral gangrene in polyarteritis nodosa.

PMID- 1974489
TI  - Immunohistochemical studies of Vogt-Koyanagi-Harada disease with sunset sky
      fundus.
AB  - We studied Vogt-Koyanagi-Harada disease (VKH) with sunset sky fundus using
      histopathology and immunohistochemical methods. The materials examined were 4
      eyes obtained at autopsy on two patients with VKH. The first patient died 32
      months after the onset of VKH, and the other 7 years after onset. Histopathology
      of the eyes showed scattering infiltration of lymphocytes in the thickened
      choroid with a remarkable disappearance of choroidal melanocytes. T and B
      lymphocytes were identified by immunohistochemistry, using monoclonal antibodies.
      Approximately 70% of the lymphocytes were T cells. In the case 1 patient, the
      ratio of CD4+ to CD8+ T cells was 2 to 3. Thus, the evidence of T and B
      lymphocytes in these uveal tissues indicates that the inflammation remained
      active even at the convalescent stage.

PMID- 1974491
TI  - Treatment of a pigmented lesion induced by a Pelagia noctiluca sting.
AB  - A young man had persistent hyperpigmentation on the face following a jellyfish
      (Pelagia noctiluca) sting four years previously. This localized lesion resolved
      within forty days after topical hydroquinone (1.8 percent) therapy was
      instituted. This case is presented to demonstrate that persistent
      hyperpigmentation occurring after coelenterate stings can be treated with a
      topical bleaching agent.

PMID- 1974492
TI  - [Augmentation plastic surgery of the hard tissue].

PMID- 1974494
TI  - Changes in thyroglobulin release-stimulating activity (Tg-RSA) in immunoglobulin
      G from patients with Graves' disease during therapy with thionamide drug.
AB  - We have reported previously a new method for detecting thyroglobulin release
      stimulating activity (Tg-RSA) by human thyroid monolayer cells in IgGs from
      Graves' patients. We report here changes in Tg-RSA in sera of patients during
      treatment with thionamide drug. Nineteen untreated patients had their Tg-RSA,
      TSAb, TBII and serum Tg concentration (STg) followed up. Before treatment, Tg-RSA
      and TSAb were positive in all 19 patients. Three of them were TBII negative.
      During treatment with thionamide, of 16 patients who had positive Tg-RSA, TSAb
      and TBII before treatment, 6 patients continued so during the period of
      observation. Of the remaining 10 patients, 8 became TBII negative. TSAb only was
      found negative in one patient and Tg-RSA only declined to negative in another
      patient. Three patients whose TBII was initially negative, were observed to be
      negative in all three indicators after treatment. STg was higher than normal in
      all patients before therapy and changes in Tg-RSA in almost all patients were
      parallel with those in STg during treatment. From the observation during
      treatment with thionamide, our results suggest that Tg-RSA in Graves' patients
      appears to have similar properties to TSAb.

PMID- 1974493
TI  - Tolerance to oral H2-receptor antagonists.
AB  - The acid-inhibitory action of H2-receptor antagonists was shown to decrease after
      one to two weeks of dosing in healthy volunteers. This tolerance was evaluated in
      three randomized, placebo-controlled trials with the H2-receptor antagonists
      famotidine, 40 mg given after the evening meal for 28 days; ranitidine, 300 mg
      four times a day for seven days followed by 300 mg at night until day 28; and
      ranitidine, 300 mg three times a day vs 300 mg at night for 14 days. Continuous
      24-hr pH monitoring with glass electrodes was performed under fed conditions. The
      median 24-hr pH decreased from 3.2 on day 1 with famotidine 40 mg to 1.9 on day
      28 (P less than 0.0012). After seven days of dosing with ranitidine 300 mg four
      times a day the median 24-hr pH dropped from 5.0 on day 1 to 3.0 on day 7 (P less
      than 0.001) and then to 2.2 with ranitidine 300 mg at night on day 28. With
      ranitidine 300 mg three times a day the median 24-hr pH fell from 4.3 on day 1 to
      2.4 on day 14 (P less than 0.0005). With ranitidine 300 mg at night the
      respective pH values were 2.5 and 1.8 (P less than 0.003). Tolerance to H2
      receptor antagonists given in a single evening dose was only evident during the
      night, whereas tolerance occurred throughout the day and night with the three-
      and four-times-a-day regimens. A large increase in the interindividual
      variability of pH response was seen during the nighttime.

PMID- 1974495
TI  - Plasma levels and urinary excretion of lormetazepam in patients with liver
      cirrhosis and in healthy volunteers.
AB  - Plasma levels and urinary excretion of lormetazepam (Noctamid-ampoules; 2 mg/10
      ml) were studied after i.v. (0.015 mg/kg b.w.) and after p.o (0.03 mg/kg b.w.)
      administration of the drug to five patients with cirrhosis of the liver (C) and
      to five young male volunteers (N). The cirrhotic patients exhibited higher drug
      plasma levels (Cmax p.o.: 11-43 ng/ml [C] vs. 11-16 ng/ml [N]) and higher AUC0-24
      values of the unchanged drug (i.v.: 66-102 ng.h/ml [C] vs. 54-72 ng.h/ml [N];
      p.o.: 83-188 ng.h/ml [C] vs. 74-113 ng.h/ml [N]). The absolute bioavailability
      was increased in the C-group with 57-134% vs. 52-84% [N]. The total plasma
      clearance of lormetazepam was 3 ml/min/kg in the C-group and 4 ml/min/kg in the N
      group and thus within the range known for elderly and young male subjects.
      Conversely to the parent compound, the AUC-figures of its 3-OH-glucuronide were
      higher in the N-group (346-434 ng.h/ml) than in the C-group (149-371 ng.h/ml). In
      24 h pooled urine samples of both groups, the glucuronide of lorazepam, the N
      demethylated metabolite, accounted for approximately 5-14% of the dose fraction
      excreted as lormetazepam glucuronide. Apart from increased levels of the
      unchanged drug due to porto-systemic shunt and/or disease-dependent lower
      glucuronidation rate, the pharmacokinetics of lormetazepam were not altered in
      cirrhotic patients. It can therefore be concluded that for this group of patients
      the drug can be administered according to the same dose regimen as that used for
      normal subjects.

PMID- 1974496
TI  - Hemodynamic profile of carvedilol.
AB  - Several so-called multiple-action compounds have been developed, such as
      medroxalol (alpha and beta blockade, and beta-2 stimulation), celiprolol (alpha-2
      and beta-1 blockade, and beta-2 stimulation) and carvedilol (beta blockade and
      vasodilatation) for the treatment of patients with arterial hypertension and with
      coronary heart disease. Carvedilol exerts relatively uniform peripheral effects,
      i.e. a reduction of both systolic and diastolic blood pressure at rest and during
      exercise, and a decrease in the resting and exercise heart rate. Blood pressure
      fall due to carvedilol may be induced by its vasodilating effect, as documented
      by measurements of forearm blood flow and peripheral vascular resistance.
      Moreover, renal hemodynamics does not seem to be significantly altered by
      carvedilol. Carvedilol may also produce an improvement of the LV contractile
      status in patients with CHD and impaired LV function, mainly due to afterload
      reduction, in addition to its antianginal effect, which is due mainly to the beta
      blocking properties of this substance. From the studies mentioned it may be
      concluded that carvedilol is a useful and promising drug for treating patients
      with both arterial hypertension and with coronary artery disease.

PMID- 1974497
TI  - Pharmacological characteristics of the stereoisomers of carvedilol.
AB  - The racemic compound carvedilol possesses two complementary pharmacological
      effects, vasodilation and beta-blockade. The R- and S-enantiomers of carvedilol
      and the racemate were investigated with respect to the beta-blocking,
      vasodilating, and hypotensive actions. In agreement with results obtained with
      other beta-blockers, only the S-enantiomer of carvedilol exerts beta-blocking
      effects. In contrast, no substantial difference between the enantiomers could be
      seen with respect to alpha-blockade. The greater hypotensive activity of S
      carvedilol may be attributed to beta-blockade, which inhibits counter-regulatory
      mechanisms provoked by vasodilation. From these results it is concluded that
      there is a rationale for using carvedilol as the racemate. Using the S-enantiomer
      would lead to relatively strong beta-blockade with only a weak vasodilating
      effect. The R-enantiomer alone would act only as a hypotensive agent without beta
      blockade.

PMID- 1974498
TI  - Stereoselective disposition of carvedilol in man after intravenous and oral
      administration of the racemic compound.
AB  - The racemic compound carvedilol is a multiple-action oral antihypertensive drug
      that exhibits both vasodilator and non-selective beta-adrenergic blocking
      activities. The effects of the levorotatory S-enantiomer [S(-)-CARV] are
      vasodilatation and beta-blockade. The R(+)-enantiomer [R(+)-CARV] is a pure
      vasodilating agent. Quantitative determination of the enantiomers in human plasma
      by HPLC was carried out after formation of diastereoisomers with the chiral
      reagent 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl isothiocyanate (GITC). The
      pharmacokinetics of the enantiomers were studied following i.v. (12.5 mg in 1 h)
      and p.o. (50 mg) administration of racemic carvedilol in ten healthy male
      subjects according to a randomized crossover design. The AUCs of S(-)-CARV were
      significantly lower than those of R(+)-CARV after both i.v. and p.o.
      administration. The systemic clearance of the two enantiomers was significantly
      different, whereas half-lives and apparent distribution volumes were comparable.
      Following p.o. administration, the absolute bioavailability (31.1% and 15.1%,
      respectively) and maximal plasma concentrations of R(+)-CARV were twice those of
      S(-)-CARV. A similar difference was found in the half-lives. A close correlation
      existed between enantiomeric ratios after i.v. and after p.o. administration,
      demonstrating slight intraindividual variability. The preferential systemic
      clearance of the S(-)-enantiomer suggests stereoselective hepatic metabolism of
      carvedilol, becoming especially apparent after p.o. administration. The small
      intrasubject variability in enantiomer ratios indicates a relatively constant
      relation of beta-blockade to vasodilation during chronic treatment.

PMID- 1974499
TI  - Hemodynamic differences between carvedilol and labetalol in the cutaneous
      circulation.
AB  - The effects of labetalol and carvedilol on local cutaneous microvascular
      perfusion and calculated local cutaneous microvascular resistance were
      investigated in anesthetized rats at submaximal doses that produced equivalent
      reductions in blood pressure and heart rate. Labetalol decreased cutaneous
      perfusion (-25% +/- 3%) without significantly affecting cutaneous vascular
      resistance (-6% +/- 3%). In marked contrast, carvedilol dramatically increased
      cutaneous perfusion (+64% +/- 9%) and significantly reduced cutaneous vascular
      resistance (-57% +/- 3%). These results suggest that carvedilol and labetalol
      possess differences in the mechanisms by which they produce vasodilation in vivo.

PMID- 1974500
TI  - Effects of carvedilol on common carotid arterial flow, peripheral hemodynamics,
      and hemorheologic variables in hypertension.
AB  - The effects of a beta-blocker, carvedilol, on peripheral hemodynamics and
      hemorheologic parameters were evaluated in 11 geriatric patients with essential
      hypertension [3 men and 8 women aged 62-79 years (mean, 68.6 years)]. Carvedilol
      was given orally after breakfast at a dose of 10 or 20 mg daily for 8 weeks.
      Peripheral hemodynamics, the common carotid arterial flow, and hemorheologic
      parameters were determined twice prior to administration and after 4 and 8 weeks
      of carvedilol treatment. The common carotid arterial flow was determined using
      the pulsed Doppler method. Peripheral hemodynamics were assessed by venous
      occlusion plethysmography. The hemorheologic parameters assessed include
      erythrocyte aggregation, erythrocyte deformability, plasma viscosity, whole-blood
      hematocrit, and platelet function tests. Erythrocyte aggregation was measured
      using an Erythrocyte Aggregometer MA-1 (Myrenne, USA), taking a high shear rate
      of 600 s-1 and a low shear rate of 3 s-1 as the indices. Statistical comparisons
      of values before and after carvedilol administration were made using the paired
      Student's t-test. Systolic and diastolic blood pressure were decreased by
      carvedilol. The common carotid arterial flow was increased, and peripheral
      hemodynamics were improved by carvedilol. Erythrocyte aggregation (measured at
      both a high and a low shear rate) and plasma viscosity were decreased,
      erythrocyte deformability was increased, and levels of circulating platelet
      aggregates were also improved by carvedilol. This improvement of hemorheologic
      variables may contribute to prevention of the initiation and progression of
      thrombosis and atherosclerosis in geriatric patients with essential hypertension.

PMID- 1974501
TI  - Effects of carvedilol on cerebral blood flow and its autoregulation in previous
      stroke patients with hypertension.
AB  - We studied the effects of oral carvedilol (20 mg/day) on cerebral blood flow
      (CBF) and CBF autoregulation in ten previous stroke patients with hypertension.
      Measurement of CBF was done by the argon inhalation method. CBF autoregulation
      was also studied by the (A-V)O2 method after stepwise reduction in systemic blood
      pressure. After 1 week of carvedilol administration, the mean arterial blood
      pressure showed an 18% decrease, with no significant changes in CBF, CBF
      autoregulation, or other cerebral circulation parameters. From these findings, it
      can be said that carvedilol is a potent antihypertensive agent that does not
      affect cerebral circulation parameters.

PMID- 1974502
TI  - Influence of carvedilol and propranolol on coronary blood flow.
AB  - A total of 17 patients with angiographically proven coronary artery disease and
      at least one stenosis blocking greater than or equal to 70% of the left anterior
      descending or circumflex artery were included in a double-blind, randomized
      study. They received either 5 mg carvedilol or 6 mg propranolol intravenously.
      Heart rate, aortic pressure, mean coronary sinus pressure and coronary flow
      (thermodilution) were measured and coronary resistance and the rate-pressure
      product were calculated before and 25 min after injection. Carvedilol
      significantly (P less than 0.05) lowered the heart rate (mean, 76 to 69
      beats/min), aortic pressure (mean, 153/80-135/72 mm Hg), rate-pressure product
      (mean, 117-93 mm Hg/min), and coronary flow (mean, 114-94 ml/min). Coronary
      resistance (mean, 0.97-1.07 mm Hg x min/ml) and coronary flow related to the rate
      pressure product (mean, 1.0-1.02 ml/mm Hg) showed no significant change after
      carvedilol treatment. Propranolol lowered the heart rate (mean, 76-64/min; P less
      than 0.05) and rate-pressure product (mean, 109-96 mm Hg/min; not significant).
      Aortic pressure (mean, 145/72-147/74 mm Hg), coronary flow (mean 109-101 ml/min),
      coronary resistance (mean, 1.1-1.2 mm Hg x min/ml), and coronary flow related to
      the rate-pressure product (mean, 1.12-1.19 ml/mm Hg) showed no significant change
      after propranolol administration. Following single application, carvedilol
      lowered the rate-pressure product more markedly than did propranolol on account
      of its acute blood-pressure-lowering effect. No differences in the hemodynamic
      effects of carvedilol and propranolol were found. Neither drug seems to influence
      the adaption of coronary flow to myocardial oxygen demand.

PMID- 1974503
TI  - The use of carvedilol in elderly hypertensive patients.
AB  - Carvedilol, a beta-blocking drug with vasodilator activity, has been used in 4
      studies in 107 elderly patients with essential hypertension and has reduced blood
      pressure effectively. In the first study the pharmacokinetics and clinical
      response were compared between 21 patients greater than 65 years of age and 8
      patients aged 35-50 years). The peak blood levels, time to maximal concentration,
      area under the curve, half-life and trough level of the drug with chronic
      administration did not differ. The clinical responses to the drug were similar,
      with a greater fall in systolic blood pressure in the older group. However the
      initial systolic blood pressure in the older group was higher. Carvedilol was
      compared with metoprolol, pindolol and nitrendipine in elderly patients. The
      responses to carvedilol were at least equal to those obtained with the other
      drugs. Control was achieved in the three studies with once-daily therapy. There
      was no significant postural hypotensive effect. A feature of all studies was the
      large number of patients who responded to carvedilol. The side-effect profile of
      the drug was acceptable; headache and dizziness were more common than with
      placebo or the comparison drugs and were frequently associated. There were no
      adverse biochemical effects and the lipid profile was not altered. Carvedilol is
      an effective antihypertensive drug that lowers blood pressure equally well in the
      young and the old.

PMID- 1974504
TI  - Effects of carvedilol on serum lipids in hypertensive and normotensive subjects.
AB  - The effects of carvedilol (an alpha.beta-blocker) on lipid metabolism were
      assessed in addition to its hypotensive effect. The subjects were 18 men and 18
      women, 20 with hypertension and 16 normotensives with other conditions requiring
      carvedilol treatment. They were aged from 31 to 79 years and were given a daily
      dose of 5-20 mg carvedilol (average, 9.7 mg/day) for 12 weeks. Significant falls
      were seen in blood pressure and heart rate after 12 weeks in the hypertensive
      subjects (mean +/- SE) (systolic: from 164 +/- 2 to 141 +/- 2 mm Hg, P less than
      0.001; diastolic: from 98 +/- 1 to 85 +/- 2 mm Hg, P less than 0.001; heart rate:
      from 71 to 65 beats/min, P less than 0.001). Smaller changes in blood pressure
      and heart rate were seen in the normotensive subjects, with the fall in systolic
      pressure being significant (from 143 +/- 3 to 135 +/- 2 mm Hg, P less than 0.01).
      There were no significant changes in the overall serum total cholesterol,
      triglycerides, high-density lipoprotein (HDL) cholesterol, and phospholipid
      levels. In the subgroup with a pretreatment serum triglyceride level of greater
      than 150 mg/dl, a significant fall of 52.1 mg/dl was seen (P less than 0.05).
      Lipoprotein analysis showed a significant fall in alpha-lipoprotein levels (P
      less than 0.05). The atherogenic index did not change significantly, and it was
      concluded that carvedilol was an effective antihypertensive agent that produced
      no adverse effects and possibly had beneficial effects on lipid metabolism.

PMID- 1974505
TI  - Safety and antihypertensive efficacy of carvedilol and atenolol alone and in
      combination with hydrochlorothiazide.
AB  - Carvedilol has been shown to be effective and safe in patients with essential
      hypertension when given as monotherapy. In this double-blind, randomized, group
      comparative study, 2 groups of 59 patients with mild to moderate essential
      hypertension [median supine systolic/diastolic blood pressure at baseline
      (SBP/DBP), 168/105 mmHg] were treated with either 25 mg carvedilol once daily
      (o.d.) or 50 mg atenolol o.d. for 4 weeks. Responders at 4 weeks (DBP, less than
      90 mmHg) terminated the study. Nonresponders continued the study.
      Hydrochlorothiazide (HCTZ) was added at 25 mg o.d. for a further 6 weeks. The
      median blood pressure decreased under monotherapy with carvedilol (n = 59) from
      167/105 at baseline to 155/94 mmHg after 4 weeks, and in the atenolol group (n =
      59) it decreased from 168/105 to 162/97 mmHg. The patients who received
      carvedilol in combination with HCTZ and were evaluated for efficacy (n = 38)
      showed a decrease in SBP/DBP from 156/97 at the end of monotherapy to 145/88 mmHg
      after 10 weeks; the combination of atenolol with HCTZ (n = 44) reduced BP from
      162/97 to 147/88. Both carvedilol and atenolol were safe when given either alone
      or in combination with HCTZ. In conclusion, after long-term administration, 25 mg
      carvedilol o.d. and 50 mg atenolol o.d. significantly reduced both SBP and DBP
      over 24 h. The addition of HCTZ led to a further increase in antihypertensive
      efficacy. Combined treatment with carvedilol or atenolol and HCTZ was very well
      tolerated, without hypotensive events or relevant changes in objective safety
      parameters.

PMID- 1974507
TI  - The safety of adding carvedilol to hypertensive patients inadequately treated
      with diuretics.
AB  - A single-blind, single-center study was conducted to investigate the short-term
      safety and efficacy of carvedilol, a new cardiovascular agent, when added to 25
      mg hydrochlorothiazide (HCTZ) as combination therapy for patients inadequately
      treated with HCTZ alone. A total of 18 patients entered the baseline study phase,
      during which they received 25 mg HCTZ once daily for 4 weeks; 16 of these
      patients (8 men and 8 women) entered the combination treatment phase. All
      patients had a supine diastolic blood pressure (DBP) of greater than or equal to
      95 mm Hg prior to receiving the first dose of combination treatment. Combination
      treatment consisted of 25 mg HCTZ plus 12.5 mg carvedilol once daily for 2 days,
      followed by a forced titration of the carvedilol dose to 25 mg for 7 days. After
      2 days of 12.5 mg carvedilol plus 25 mg HCTZ once daily, mean trough blood
      pressure was reduced as compared with baseline values. Of 16 patients, 6 (38%)
      achieved a trough supine DBP of less than 90 mm Hg. After 1 additional week of
      combination therapy with 25 mg carvedilol, 8 of 15 patients (53%) achieved a
      trough supine DBP of less than 90 mm Hg and 14 of 15 patients (93%) achieved that
      of less than 95 mm Hg. At each visit during the combination treatment phase, the
      acute reduction in blood pressure was greatest during the first 2 h after dosing.
      The heart rate was minimally affected by combination treatment with carvedilol at
      either trough levels or acutely after dosing. Nine patients experienced adverse
      events during combination treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1974506
TI  - Efficacy and safety of carvedilol in comparison with atenolol in hypertensive
      patients pretreated with hydrochlorothiazide.
AB  - Carvedilol [25 mg once daily] (o.d.) was compared to atenolol (50 mg o.d.) as an
      adjunct to pre-existing hydrochlorothiazide (HCTZ) monotherapy in patients with
      mild to moderate hypertension [diastolic blood pressure (DBP), 100-115 mm Hg].
      After a placebo run-in phase of 2 weeks, 131 patients received 25 mg HCTZ o.d.
      for 4 weeks. In all, 122 patients were transferred to the double-blind phase, in
      which 25 mg carvedilol or 50 mg atenolol was randomly added to HCTZ. After an
      additional 6 weeks of treatment, 112 patients were evaluable for efficacy (C/HCTZ
      group, n = 54; A/HCTZ group, n = 58). Blood pressure was measured and the heart
      rate was counted before medication, at 2-week intervals throughout the trial, and
      2 h after medication on the 1st and the last day of the combination treatment
      period. Serum lipids were measured in addition to routine laboratory variables. A
      therapeutic response was defined as a reduction in supine and standing diastolic
      blood pressure to values of less than 90 mm Hg. In a relatively low number of
      patients (6 of 131), a response as defined above was achieved with HCTZ alone.
      This may be accounted for by the fact that patients were required to have a
      diastolic blood pressure of at least 100 mg Hg and by the relatively short period
      of monotherapy. The two groups of patients receiving different combination
      treatments were well matched for demographic data and blood pressure values
      before the adjunct was added. In both groups there was a marked additional blood
      pressure decrease on the initiation of combined treatment.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1974509
TI  - Safety and efficacy of once-daily carvedilol vs twice-daily labetalol in mild to
      moderate hypertension.
AB  - A multicenter, randomized, double-blind, parallel-group trial of 8 weeks'
      duration was designed to compare the efficacy and safety of once-daily carvedilol
      with that of twice-daily labetalol in patients with essential hypertension. A
      total of 61 patients (13 women and 48 men) aged 26-64 years (mean +/- SEM = 49.6
      +/- 1.3 years) were enrolled. All patients had mild to moderate hypertension,
      defined as diastolic blood pressure (DBP) of 95-114 mm Hg at the end of a 1- to 2
      week single-blind placebo period. In all, 30 patients received carvedilol (25 mg
      once daily) and 31 received labetalol (200 mg twice daily). The initial dose
      could be doubled for both treatment groups at day 29 if the DBP was greater than
      90 mmHg on days 28 and 29. Hemodynamic parameters, including supine and standing
      DBP, systolic blood pressure (SBP), and heart rate (HR), were measured and safety
      was evaluated at baseline and at days 14, 28, and 56 at the end of the dosing
      interval. In all, 3 patients on carvedilol and 4 patients on labetalol required
      upward dose titration after 1 month. At the end of the trial, 26 of 30 carvedilol
      treated patients and 27 of 31 labetalol-treated patients (87% of each group) had
      a supine DBP of less than or equal to 90 mm Hg. On day 56, mean decreases in
      supine DBP, SBP, and HR in the carvedilol group were 18.5 and 23.4 mm Hg and 11
      beats/min, respectively, from baseline values of 101.6 and 163.8 mm Hg and 80
      beats/min, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1974508
TI  - Efficacy and safety of carvedilol in renal hypertension. A multicenter open
      trial.
AB  - Carvedilol, a novel beta-blocker with a vasodilating action, was given either
      alone (monotherapy) or with diuretics (combination therapy) to 42 patients with
      renal hypertension. The hypotensive effect, safety, and optimal dose were
      investigated. In all, 23 untreated patients (16 men and 7 women; average age,
      56.4 +/- 2.5 years) made up the monotherapy group and 19 diuretic-treated
      patients (11 men and 8 women; average age, 56.4 +/- 2.5 years) comprised the
      combined therapy group. All subjects had an initial blood pressure (BP) of
      greater than 160/95 mmHg and were started on 5 mg/day oral carvedilol. The dose
      was gradually increased to a maximum of 20 mg/day, or until either the BP was
      reduced to less than 149/89 mmHg or the reduction in mean BP was greater than 13
      mmHg compared with baseline levels. The total study period was 8 weeks. With
      monotherapy, the BP and heart rate decreased significantly from 167/102 to 150/94
      mmHg and from 81 to 74 beats/min, respectively. With combined therapy, the BP and
      heart rate fell significantly from 176/103 to 142/85 mmHg and from 81 to 70
      beats/min, respectively. Responders were defined as subjects with a BP of less
      than or equal to 149/89 mmHg or those showing a fall of greater than or equal to
      13 mmHg in mean BP. Responders accounted for 52.2% of the monotherapy group and
      73.6% of the combination therapy group. Orthostatic hypotension was not seen in
      either group. Serum creatinine and blood urea nitrogen (BUN) levels were not
      altered by administration of carvedilol. Dizziness was noted by 1 of the 23
      subjects in the monotherapy group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1974510
TI  - Blood-pressure-lowering effect of carvedilol vs nitrendipine in geriatric
      hypertensives.
AB  - Carvedilol and nitrendipine were given for 12 weeks in a double-blind study to 81
      elderly patients (greater than or equal to 60 years) with essential hypertension.
      The effects on blood pressure were measured (Riva Rocci) before medication and
      after 2 h with the patient in a lying and standing position after 4 weeks of
      placebo therapy as well as after 4, 8 and 12 weeks of treatment. Carvedilol (25
      mg/o.d.) reduced blood pressure measured in the supine and erect position very
      successfully, similar to the reduction achieved with nitrendipine (20 mg/o.d.),
      without influencing the pulse rate. Both substances were well tolerated.
      Carvedilol is an alternative substance for lowering high blood pressure in
      elderly hypertensive patients.

PMID- 1974511
TI  - The pharmacology of carvedilol.
AB  - Carvedilol is a potent antihypertensive agent with a dual mechanism of action. At
      relatively low concentrations it is a competitive beta-adrenoceptor antagonist
      and a vasodilator, whereas at higher concentrations it is also a calcium channel
      antagonist. The antihypertensive activity of carvedilol is characterized by a
      decrease in peripheral vascular resistance, resulting from the vasodilator
      activity of the compound, with no reflex tachycardia, as a result of beta
      adrenoceptor blockade. The antihypertensive activity of carvedilol is associated
      with an apparent "renal sparing" effect in that the reduction in mean arterial
      blood pressure does not compromise renal blood flow or urinary sodium excretion.
      Studies on the mechanism of action of carvedilol indicate that the compound is a
      potent competitive antagonist of beta 1- and beta 2-adrenoceptors with a
      dissociation constant (KB) of 0.9 nM at both beta-adrenoceptor subtypes.
      Carvedilol is also a potent alpha 1-adrenoceptor antagonist (KB = 11 nM), which
      accounts for most, if not all, of the vasodilating response produced by the
      compound. At concentrations above 1 microM, carvedilol is a calcium channel
      antagonist. This activity can be demonstrated in vivo at doses that represent the
      higher end of the antihypertensive dose-response curve. Although the calcium
      channel blocking activity of carvedilol may not contribute to the
      antihypertensive activity of the compound, it may play a prominent role in
      certain peripheral vascular beds, such as the cutaneous circulation, where marked
      increases in blood flow are observed. The data indicate that carvedilol is an
      antihypertensive agent that is both a beta-adrenoceptor antagonist and a
      vasodilator.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1974512
TI  - The role of multiple action agents in hypertension.
AB  - A 20-year follow-up study of central hemodynamics in essential hypertension at
      rest and during exercise in 61 men with uncomplicated essential hypertension has
      clearly shown that hemodynamic disturbances depend on the age of the subjects and
      the severity of the hypertensive state and that a shift in the hemodynamic
      alterations take place over time. During 10- and 20-year follow-up, central
      hemodynamics changed towards a low cardiac-index (CI)-high total peripheral
      resistance index (TPRI) pattern. With increasing age there was a gradual
      reduction in CI as well as stroke index (SI). The arteriovenous oxygen difference
      increased, particularly during exercise. The 20-year treatment with conventional
      drugs (beta-blockers and/or diuretics) did not prevent a marked increase in TPRI
      and a marked reduction in CI and SI in subjects initially 40-49 years of age. In
      recent years, beta-blockers with vasodilating activity have been introduced in
      the treatment of hypertension (labetalol, prizidilol, dilevalol and carvedilol).
      The hemodynamic effects of these compounds clearly differ from the changes
      induced during acute and chronic conventional beta-blocking treatment. In
      contrast to usual beta-blockers, these drugs reduce TPRI acutely and the
      reductions they produce in heart rate (HR) and CI are considerably lower. Our
      long-term data on labetalol (n = 15), prizidilol (n = 15) and dilevalol (n = 17)
      indicate a persistent reduction in TPRI and little or no decrease in exercise CI.
      Long-term data on carvedilol are not yet available. Approximately 70% of patients
      with mild to moderately severe essential hypertension achieved normal blood
      pressure during chronic treatment on beta-blockers with vasodilating activity.

PMID- 1974514
TI  - Acute and chronic effects of rilmenidine on baroreflex function in conscious
      dogs.
AB  - The effects of acute and chronic administration of rilmenidine on blood pressure,
      heart rate and baroreflex function were assessed in two groups of six conscious
      dogs. Baroreflex function was evaluated using increasing doses of glyceryl
      trinitrate and phenylephrine to decrease and increase blood pressure
      respectfully. Acute administration of rilmenidine (1 mg/kg p.o.) reduced (P less
      than 0.05) blood pressure and heart rate, and enhanced (P less than 0.05)
      baroreflex function to increases in blood pressure with phenylephrine, but not to
      decreases in blood pressure by glyceryl trinitrate. Following chronic
      administration of rilmenidine, blood pressure remained lowered while heart rate
      and baroreflex function returned to control values.

PMID- 1974513
TI  - Effects of carvedilol on renal function.
AB  - A randomized, double-blind, placebo-controlled study was conducted to study the
      effects of acute and chronic administration of carvedilol in essential
      hypertension, with special emphasis on renal haemodynamics and function. Acute
      administration of a single dose of 50 mg carvedilol reduced systolic and
      diastolic blood pressure without inducing reflex tachycardia. Renal blood flow
      was preserved; accordingly, renal vascular resistance was significantly reduced.
      A significant reduction in the glomerular filtration rate and filtration fraction
      was observed. Plasma renin activity (PRA) and plasma aldosterone values were not
      changed. Chronic carvedilol treatment produced a significant fall in systolic and
      diastolic blood pressure, heart rate, PRA and plasma aldosterone. Renal blood
      flow, glomerular filtration rate and filtration fraction also remained unchanged;
      renal vascular resistance decreased significantly. It is concluded that
      carvedilol possesses definite antihypertensive and renal vasodilating properties,
      both acutely and after chronic treatment.

PMID- 1974515
TI  - Effect of anticonvulsant treatment on kainic acid-induced increases in peptide
      levels.
AB  - The influence of anticonvulsant treatment upon (1) chronically increased seizure
      susceptibility, (2) on late increases in peptide levels and (3) on seizure
      induced brain damage was investigated during various stages of acute kainic acid
      (10 mg/kg i.p.)-induced seizures. The seizures were interrupted at various stages
      of the syndrome (50 min to 24 h after injection of the toxin) by injecting
      thiopental (50 mg/kg i.p.) or the excitatory amino acid antagonist, MK-801 (10
      mg/kg i.p.). The increase in neuropeptide Y and somatostatin levels in the
      frontal cortex could be prevented by early injection of either anticonvulsant (up
      to 180 min after kainic acid). No protection against the increase in peptide
      levels was observed when the anticonvulsants were applied later. Kainic acid
      induced neuronal damage in the amygdala, with glutamate decarboxylase as a
      neurochemical marker, was entirely prevented by interrupting seizures up to 2 h
      after kainic acid. Partial protection (about 40-50%) was even found when the
      anticonvulsant treatment was applied after the acute syndrome, as late as 8 h
      after kainic acid injection. Chronically increased seizure susceptibility induced
      by kainic acid was not prevented, even by early injection (90 min after kainic
      acid) of the anticonvulsant drugs. The data indicate that (1) the late increase
      in seizure susceptibility may be initiated early after injection of kainic acid.
      (2) the late increase in peptide levels may be related to the frequency of acute
      seizures rather than to a change in seizure threshold or brain damage and (3)
      even late anticonvulsant therapy may antagonize seizure-induced brain damage in
      the amygdala.

PMID- 1974516
TI  - The potential antipsychotic activity of the partial dopamine receptor agonist
      (+)N-0437.
AB  - The (+) enantiomer of the very potent and selective dopamine D-2 agonist, 2-(N
      propyl-N-2-thienylethylamino)-5-hydroxytetralin (N-0437), displays partial
      agonistic activity at dopamine D-2 receptors. In this study (+)N-0437 was
      investigated for its antagonistic activity at postsynaptic DA receptors in four
      behavioural tests which are commonly used to evaluate potential neuroleptic
      activity, i.e. d-amphetamine-induced stereotypy, passive avoidance responding,
      intracranial self-stimulation behaviour, and catalepsy. (+)N-0437 (25-50
      mumol/kg) was active in the first three models, but did not cause catalepsy.
      Haloperidol, which was used as a reference compound for classical DA antagonists,
      showed clear activity in all four models at low doses (0.5-1.0 mumol/kg). (-)N
      0437, a full D-2 agonist, displayed no activity in these behavioural models.
      These results suggest that (+)N-0437 could be used to examine the hypothesis that
      the use of partial agonists could provide a new treatment for schizophrenia.

PMID- 1974517
TI  - The l-enantiomer of nebivolol potentiates the blood pressure lowering effect of
      the d-enantiomer.
AB  - In this study the effect of l-nebivolol on the blood pressure lowering action of
      d-nebivolol was investigated after intraperitoneal administration of the drugs to
      spontaneously hypertensive rats. Doses of l-nebivolol which did not affect blood
      pressure when given alone potentiated the decrease in systolic and diastolic
      blood pressure induced by 1.25 mg.kg-1 d-nebivolol. The potentiating effect of l
      nebivolol was seen at doses higher than 0.16 mg.kg-1. At 1.25 mg.kg-1 d-nebivolol
      significantly reduced the heart rate, an effect which was not potentiated by l
      nebivolol in doses up to 1.25 mg.kg-1. Higher doses of l-nebivolol (2.5 and 5.0
      mg.kg-1) in combination with 1.25 mg.kg-1 d-nebivolol not only lowered the blood
      pressure further, but also significantly reduced the heart rate; thus at these
      doses the enantiomers together exerted more pronounced beta 1-adrenoceptor
      blocking properties. This is probably disadvantageous, because d,l-nebivolol has
      been shown to decrease arterial blood pressure in hypertensive patients and
      animals before it reaches its maximal beta 1-adrenoceptor blocking effect.
      Therefore, the racemic mixture of 50% d-nebivolol and 50% l-nebivolol seems to
      contain the two compounds in near optimal proportions for an antihypertensive
      effect.

PMID- 1974519
TI  - Activity and gene expression of transglutaminase in guinea pig liver during the
      postnatal growing phase.
AB  - During the postnatal growing phase from birth to 7 weeks old, the cytosolic
      transglutaminase activity of guinea pig liver increased 3.8-fold. The enzyme
      activity in the particulate fraction increased slightly. Immunoblot analyses
      showed that the postnatal increase in the activity was correlated with in
      increase in the enzyme protein. The quantity of mRNA of the liver
      transglutaminase did not change significantly during the postnatal growing phase
      examined. These results indicated that transglutaminase may be involved in the
      postnatal development of guinea pig liver and that the amount of transglutaminase
      in the postnatal liver may be controlled post-transcriptionally.

PMID- 1974518
TI  - The sigma [corrected] ligand rimcazole antagonises (+)SKF 10,047, but not (+)3
      PPP, in the mouse isolated vas deferens.
AB  - We have characterized the actions of several sigma receptor ligands on the
      electrically evoked, neurogenic contractions of the mouse isolated vas deferens.
      (-)SKF 10,047 was significantly more potent than (+)SKF 10,047 in potentiating
      twitch contractions and was equipotent with (+)3-PPP. Rimcazole (1 and 3 microM)
      antagonised the potentiation induced by 100 microM (+)SKF 10,047 and, to a lesser
      extent, that induced by 30 microM (-)SKF 10,047 but increased that elicited by
      (+)3-PPP (30 microM). This apparent contradiction may arise from sigma agonists
      acting in this tissue at both sigma and non-sigma sites.

PMID- 1974520
TI  - Human chorionic gonadotropin alpha and human cytomegalovirus promoters are
      extremely active in the fission yeast Schizosaccharomyces pombe.
AB  - We have investigated the transcriptional activity of human cytomegalovirus,
      herpes thymidine kinase, human chorionic gonadotropin alpha, somatostatin,
      immunoglobulin kappa chain, alpha crystallin, albumin and interferon-beta
      promoters in the fission yeast Schizosaccharomyces pombe. Among these, the human
      cytomegalovirus, human chorionic gonadotropin alpha, and somatostatin promoters
      were found to be very active, approximately 11-, 9-, and 0.9-fold as active as
      the SV40 early promoter, respectively. The remainder of the promoters studied
      were weak, having only 10-20% of the SV40 promoter activity. Primer extension
      analysis showed that the strong promoters initiated transcription in S. pombe at
      the same sites as in mammalian cells, indicating the high similarity between both
      transcriptional systems.

PMID- 1974521
TI  - Inhibition of development of Na(+)-dependent hexose transport in renal epithelial
      LLC-PK1 cells by differentiation-stimulating factor for myeloid leukemic
      cells/leukemia inhibitory factor.
AB  - Differentiation-stimulating factor (D-factor)/leukemia inhibitory factor is a
      cytokine inducing differentiation of mouse myeloid leukemic M1-T22 cells. The
      effect of recombinant human D-factor on growth and differentiation of pig kidney
      LLC-PK1 cells was examined. LLC-PK1 cells did not concentrate alpha
      methylglucoside during their early growth in culture but developed the capacity
      to concentrate this hexose as they reached confluence and their growth rate
      decreased. Purified D-factor caused dose-dependent inhibition of the development
      of this concentrative capacity. It did not affect the growth rate of the cells,
      but inhibited the formation of multicellular domes in confluent cultures. LLC-PK1
      cells were found to have high-affinity binding sites (831 per cell) for D-factor
      with a dissociation constant of 197 pM.

PMID- 1974523
TI  - Neurotransmitter release.
AB  - Axon terminals release more than one physiologically active substance. Synaptic
      messengers may be stored in two different types of vesicles. Small electron
      lucent vesicles mainly store classical low molecular weight transmitter
      substances and the larger electron-dense granules store and release proteins and
      peptides. Release of the two types of substances underlies different
      physiological control. Release of messenger molecules from axon terminals is
      triggered by influx of Ca2+ through voltage sensitive Ca2+ channels and a rise in
      cytosolic Ca2+ concentrations. Neither the immediate Ca2+ target(s) nor the
      molecular species involved in synaptic vesicle docking, fusion and retrieval are
      known. It is, however, likely that steps involved in the molecular cascade of
      transmitter release include liberation of vesicles from their association with
      the cytonet and phosphorylation by protein kinase C of proteins which have the
      ability to alter between membrane bound and cytoplasmic forms and thus facilitate
      or initiate the molecular interaction between synaptic vesicles and the plasma
      membrane.

PMID- 1974522
TI  - Amino acid sequence of the Ca2(+)-triggered luciferin binding protein of Renilla
      reniformis.
AB  - The complete amino acid sequence of the Ca2(+)-triggered luciferin binding
      protein (LBP) of Renilla reniformis has been determined. The apoprotein has an
      unblocked amino terminus and contains 184 residues with a calculated Mr of
      20,541. LBP is a member of the EF-hand superfamily of Ca2(+)-binding proteins and
      bears three predicted EF-hand domains. The sequence and organization of EF-hand
      domains are similar to those of the Ca2(+)-dependent photoprotein, aequorin.

PMID- 1974525
TI  - Symphysis-fundal height measurement--a reliable parameter for assessment of fetal
      growth.
AB  - Intrauterine growth retardation (IUGR) is one of the major causes of perinatal
      mortality in countries like India. Fundal height traditionally measured in
      relation to umbilicus and xiphisternum is of little value in predicting the fetal
      growth. Some workers have found that symphysis fundal height (SFH) measurements
      could be useful in screening pregnancies for growth retardation. A prospective
      study was taken up in 109 pregnant women attending the antenatal clinic of our
      Institution. Serial measurements of SFH, abdominal girth, double abdominal wall
      thickness (DAWT) and maternal weight gain were recorded. SFH measurements
      obtained were arranged on the basis of 10th, 50th and 90th percentile and
      represented graphically. Statistical analysis showed that the coefficient of
      variation was smallest for SFH as compared to abdominal girth and maternal weight
      gain. The babies (single born) delivered were between 2600 g and 3700 g
      irrespective of whether the maternal weight gain was 143 g/week or 424 g/week.
      The abdominal wall thickness had no influence on the measurement of SFH. An
      attempt was made to develop a nomogram of SFH for our population. This is a
      simple, reliable and inexpensive method in the screening of pregnancies for IUGR.

PMID- 1974524
TI  - [The effect of growth hormone-releasing factor (GRF) on secretion of insulin,
      glucagon and somatostatin from perfused rat pancreas].
AB  - To examine the effects of growth hormone-releasing factor (GRF) on islet hormone
      release, rat pancreas was perfused. rhGRF at the concentration of 10(-7) M or
      more enhanced insulin secretion stimulated by 16.7 mM glucose, hpGRF slightly
      enhanced insulin secretion as well. The insulin secretion induced by 10(-6) M
      rhGRF was completely inhibited by 10(-6) M propranolol. rhGRF at the
      concentration of 10(-8) M or more stimulated glucagon secretion even in the
      presence of 16.7 mM glucose. The glucagon secretion stimulated by 10(-6) M rhGRF
      was inhibited in the early period but increased thereafter by 10(-6) M
      propranolol. 10(-6) M rhGRF slightly stimulated glucagon secretion in the
      presence of 16.7 mM glucose when STZ diabetic rat pancreas was perfused. rhGRF at
      the concentration of 10(-6) M enhanced somatostatin secretion stimulated with
      16.7 mM glucose. We concluded that rhGRF stimulated insulin, glucagon and
      somatostatin secretion and the insulin secretion was inhibited by beta-blocker.
      hpGRF stimulated insulin and glucagon secretion as well.

PMID- 1974526
TI  - Post-cesarean analgesia using a subcutaneous pethidine infusion.
AB  - A pethidine infusion administered subcutaneously using a syringe pump was
      evaluated in 118 women following cesarean section. One hundred three women (87%)
      were satisfied with their postoperative analgesia. The mean length of infusion
      was 18.8 h, and the mean total dose of pethidine was 402 mg. Twenty-seven
      patients (23%) reported no severe pain postoperatively, the remainder had on
      average 2.6 h of pain which they described as severe. Of 38 women who had had a
      previous cesarean section, 19 (50%) considered the pump to be an improvement on
      the analgesia given the previous time. There were no cases of respiratory
      depression. This mode of analgesia has advantages over conventional intramuscular
      bolus injections. It was judged acceptable to both patients and ward staff.

PMID- 1974527
TI  - Sickle trait and its association with birthweight and urinary tract infections in
      pregnancy.
AB  - The objective of this retrospective case control study was to compare pregnant
      women with sickle trait hemoglobin to their normal hemoglobin counterparts.
      Sickle trait was associated with a significant increase in bacteriuria (13.0% vs
      9.0%) and pyelonephritis (2.1% vs 1.4%). No difference was seen in birthweight
      between the two groups.

PMID- 1974528
TI  - The relative significance of colposcopic descriptive appearances in the diagnosis
      of cervical intraepithelial neoplasia.
AB  - Four hundred and seventy seven colposcopic appearances have been analysed in 252
      patients to determine their histopathological correlation and clinical efficiency
      in the diagnosis of cervical intraepithelial neoplasia (CIN). Immature
      metaplasia, cervical ectopy and cervicitis produced a considerable quotient of
      abnormal colposcopic appearances. Acetowhite epithelium had the highest
      sensitivity (92%), lowest specificity (25%) and a positive predictive value of
      61%. Mosaicism and punctation were less sensitive (30 and 38%), but more specific
      (89 and 85%), respectively and had superior positive predictive values.

PMID- 1974529
TI  - A study of the menstrual patterns of adolescents in Ile-Ife, Nigeria.
AB  - Questionnaires and interviews with 768 female students in residence at the
      Obafemi Awolowo University, Ile-Ife, Nigeria revealed that the mean and median
      ages of menarche were respectively 13.4 +/- 1.4 and 13.5 years and 80.8% had
      menstrual cycles between 25 and 35 days. The duration of menstrual bleeding was
      4.5 +/- 0.8 days; 72.3% had dysmenorrhea and 17.8% complained of nausea and
      vomiting during menstruation.

PMID- 1974530
TI  - Elevated peritoneal fluid luteinizing hormone and prolactin concentrations in
      infertile women with endometriosis.
AB  - In this study, we compared (Mann-Whitney U-test) the peritoneal fluid FSH, LH and
      PRL levels, measured by RIA, at the follicular and luteal phases of the menstrual
      cycle in women with (n = 43; age 25-44 years) and with no evidence of
      endometriosis (n = 35; age 25-39 years) who were considered as controls. Both
      follicular and luteal phase FSH concentrations of women with endometriosis were
      not statistically different (n = 22 vs 18; 0.32-5.8 vs 0.50-8.2 IU/l, P = 0.247;
      n = 13 vs 14; 0.6-6.5 vs 0.66-6.7 IU/l, P = 0.604) compared to their respective
      controls. In contrast to FSH, the concentrations of LH at follicular (n = 19 vs
      17; 3.1-34.2 vs 2.3-12.2 IU/l, P = 0.01) and luteal (n = 17 vs 15; 2.1-95.4 vs
      1.3-17.9 IU/l, P = 0.02) phases of the test group was significantly elevated at
      both phases of the cycle. With respect to differences in PRL concentrations at
      follicular phase no significant change (n = 21 vs 16; 1030-5800 vs 1305-4650
      mIU/l; P = 0.255) was observed. The greatest difference in luteal PRL
      concentrations (P = 0.007) was obtained between the women with endometriosis and
      controls (n = 17 vs 17; 1895-8600 vs 1041-5000 mIU/l). The results suggest that
      disordered synchronization of neuroendocrine mechanisms controlling LH and PRL
      may be the underlying abnormality causing infertility in our group of patients
      with endometriosis.

PMID- 1974531
TI  - Socio-biological factors influencing infertility in a rural Nigerian community.
AB  - An assessment of factors influencing infertility in a rural Nigerian community
      revealed a prevalence rate of 12.9% primary infertility. Secondary infertility
      among the subjects was 54.1%. Age, education and religion of respondents had
      statistically significant influence on infertility (P less than 0.05) but not
      income (P greater than 0.05). The correlation between age of respondents and
      infertility was statistically significant (P less than 0.05). Primary health care
      efforts aimed at implementing maternal and child health care should explore the
      traditional customs on infertility in rural areas of developing countries.

PMID- 1974532
TI  - Effectiveness of phenol-atabrine-paste (PAP) instillation for female
      sterilization.
AB  - Two groups of sterilized women, 3307 by phenol-atabrine-paste (PAP) instillation
      and 1026 by mini-lap technique, were follow-up interviewed to determine their
      relative effectiveness. PAP, if successfully performed, was as effective as the
      mini-lap. The life table pregnancy rates among successful PAP women were 0.21 and
      0.28 at 12 and 24 months, respectively. The rates among the unsuccessful PAP
      women, however, were high: 15.1 and 30.5 at 12 and 24 months, respectively. In
      spite of its distinctive advantage of being non-surgical, wider promotion of PAP
      sterilization procedure deserves caution.

PMID- 1974533
TI  - Changes in the circulating levels of hemoglobin, hematocrit, serum iron and total
      iron binding capacity after four methods of surgical tubal sterilization.
AB  - One-hundred women requesting voluntary surgical sterilization were included and
      enrolled into four groups (each n = 25). Four sterilization modalities were used
      namely: Falope ring, electrocoagulation, clip and Pomeroy ligation. The
      circulating levels of hemoglobin, hematocrit, serum iron and total iron binding
      capacity were studied before sterilization and at 3, 6 and 12 months thereafter.
      No significant changes were observed at 3 and 6 months post-sterilization. At 12
      months a significant increase in the hemoglobin and serum iron was observed with
      a significant decrease in total iron binding capacity. Falope ring, clip and
      Pomeroy ligation were of a higher rank in this context versus electrocoagulation.

PMID- 1974535
TI  - Pruritic urticarial papules and plaques of pregnancy.
AB  - The authors present a rare case of pruritic urticarial papules and plaques of
      pregnancy in a 25-year-old caucasian primigravida admitted to our department
      because of pruritus in the third trimester of gestation. Recommendations for
      management are discussed.

PMID- 1974534
TI  - Mycoplasmas among clients attending a family planning clinic in Zaria, Nigeria.
AB  - The effect of contraception in the incidence of genital tract mycoplasma
      infection was studied in 150 women practicing contraception and another 50 women
      attending a gynecological clinic, using no contraception. Using the chi-squared
      method, there was no statistically significant difference between total
      mycoplasma recovery in family planning clients versus the controls. The only
      statistically significant difference was between total positive mycoplasma in the
      oral contraceptive group versus IUD users.

PMID- 1974536
TI  - The effect of maternal age and socioeconomical background on neonatal outcome.
AB  - This population-based study examined whether the neonatal outcome of primiparae
      is determined by maternal age or by her socioeconomic background. Data on all
      births in Israel during a three-month period was made available from a nation
      wide census. Primiparae 30 years of age or older had a significantly (P less than
      0.001) higher risk of low birthweight and prematurity. Perinatal mortality rates
      and low 5-min Apgar scores were not associated with maternal age, but were
      significantly (P less than 0.001) increased for the socioeconomically
      disadvantaged parturients. Our results suggest the growth retardation and short
      gestation among older primiparae may reflect biological aging of maternal tissues
      and the effect of diseases of pregnancy such as hypertension and preeclampsia,
      found significantly (P less than 0.001) more common for these mothers. Excessive
      perinatal mortality, on the other hand, may be attributable to environmental
      disadvantage of socioeconomically deprived populations.

PMID- 1974538
TI  - Chronic utero-rectal fistula with menochezia and amenorrhea.
AB  - Utero-intestinal fistulas are commonly acute in nature and usually follow
      malignancies of the intestines. Here we report a chronic uterorectal fistula with
      uncommon symptom of cyclical rectal bleeding (menochezia) and amenorrhea.

PMID- 1974537
TI  - Severe hemolytic disease of the newborn due to anti-c.
AB  - Two cases of severe hemolytic disease of the newborn due to c-isoimmunization are
      presented. Both women were multiparous, had previous blood transfusion and high
      maternal titers of anti-c (1:1024 and 1:4036, respectively).

PMID- 1974539
TI  - Effects of amino acids on glucose disposal.
AB  - Free fatty acids are known to inhibit carbohydrate disposal and oxidation. This
      action may play an important role in the pathophysiology of insulin resistance
      and non-insulin-dependent diabetes mellitus. To investigate whether amino acids
      (AAs) have similar actions, we determined the effects of an intravenously infused
      mixture of 15 AAs on carbohydrate disposal during euglycemic-hyperinsulinemic
      clamps associated with either basal or high glucagon concentrations in healthy
      male volunteers. Plasma glucose concentration was clamped at approximately 4.7 mM
      (coefficient of variation 4.7%). Insulin infusion (7.18 pmol.kg-1.min-1) raised
      serum insulin concentrations from 36-50 pM to between 300 and 600 pM. AA
      infusions (0.5 g.kg-1.h-1.4 h) raised plasma alpha-amino N2 concentrations about
      five- to six-fold. Infusion of AAs, somatostatin (somatotropin release inhibitory
      factor, SRIF), and high-glucagon replacement (3.0 ng.kg-1.min-1) reduced the rate
      of exogenous glucose infusion needed to maintain euglycemia from 51.1 +/- 7.2
      mumol.kg-1.min-1 (saline + SRIF + high glucagon) to 28.3 +/- 11.1 mumol.kg-1.min
      1 and stimulated endogenous glucose production (from 0 to approximately 17
      mumol.kg-1.min-1). Thus, glucose disposal (exogenous infusion plus endogenous
      production of glucose) remained essentially unchanged. During infusion of AAs +
      SRIF + basal glucagon replacement (0.25 ng.kg-1.min-1), endogenous glucose
      production remained completely suppressed, and the rates of exogenous glucose
      infusion did not change (compared with saline + SRIF + basal glucagon
      replacement). The data showed that 1) hyperaminoacidemia associated with
      hyperglucagonemia stimulated endogenous glucose production despite
      hyperinsulinemia, and 2) intravenous infusion of a mixture of 15 AAs had no
      inhibitory effect on insulin-stimulated total-body glucose disposal.

PMID- 1974540
TI  - Stimulation of transcription by an Ultrabithorax protein in vitro.
AB  - The Ultrabithorax (Ubx) gene of Drosophila melanogaster encodes a family of UBX
      proteins that are thought to specify the developmental fates of segments in the
      posterior thorax and anterior abdomen by controlling the expression of a set of
      target genes. UBX proteins bind DNA in vitro, and they activate or repress
      different natural and synthetic target promoters in cultured cells. Here it is
      shown that a purified UBX protein can stimulate transcription of a synthetic
      target gene in extracts of cultured D. melanogaster cells. Stimulation is
      dependent on the presence of upstream, promoter-region binding sites but is
      independent of binding site orientation. A naturally occurring binding site
      cluster and a binding site consensus sequence consisting of TAA trinucleotide
      repeats can mediate this activation. A minimal promoter fused to such sites is
      activated by UBX, suggesting that transcriptional stimulation could result from
      an interaction between the promoter-bound protein and the general transcriptional
      machinery.

PMID- 1974542
TI  - [A method of evaluation of mental work capacity after exposure to noise].

PMID- 1974541
TI  - Role of molecular genetics in the understanding of the pathogenesis of
      hypertension.
AB  - Possible roles for molecular genetical approaches to understand the pathogenesis
      of hypertension are briefly reviewed. To elucidate observed alterations in
      hypertensive subjects at both molecular and systemic levels in a comprehensive
      way, a model (a working hypothesis) for the molecular pathogenesis of
      hypertension is proposed. Prospects for identifying restriction fragment length
      polymorphisms observed in hypertensive rats but not in normotensive rats are also
      discussed.

PMID- 1974543
TI  - Lymphocyte ectoenzyme activity compared in healthy persons and patients
      seropositive to or at high risk of HIV infection.
AB  - We measured two ectoenzymes, ecto-5'-nucleotidase (NT) and dipeptidyl peptidase
      IV (DP) in the peripheral blood lymphocytes of various groups of HIV-infected
      patients because of the previous implied relationship of these enzymes to immune
      function. NT expressed as mean nmol/h per mg protein (+/- s.d.) was significantly
      depressed in the HIV-seropositive asymptomatic (42 +/- 32; P less than 0.01) and
      AIDS groups (14 +/- 7; P less than 0.002) when compared with a healthy HIV
      seronegative male population (83 +/- 27). The NT activities in asymptomatic HIV
      seropositive and HIV-seronegative high risk groups (53 +/- 30) were not
      significantly different from one another but both groups had significantly higher
      enzyme activities than the AIDS group (P = 0.01 and less than 0.002,
      respectively). The seronegative high risk and normal healthy group had similar NT
      activities. DP activities expressed as mean nmol/h per mg protein (+/- s.d.) in
      both seropositive asymptomatic (0.188 +/- 0.038) and high risk seronegative
      (0.180 +/- 0.05) groups had higher enzyme activities than the healthy
      seronegative (0.117 +/- 0.015; P = 0.02 and 0.05, respectively) and AIDS group
      (0.096 +/- 0.036; P = 0.002 and 0.02, respectively). The healthy seronegative
      group had DP activities not significantly different to the AIDS groups. Similarly
      the high risk seronegative and healthy seropositive group had similar DP
      activities. These results taken together indicate that measurement of both DP and
      NT should be evaluated prospectively as a monitor of the clinical progression of
      HIV infection.

PMID- 1974544
TI  - Second Japanese-German Workshop on Molecular and Cellular Aspects of
      Carcinogenesis.

PMID- 1974546
TI  - Characterization by RFLP analysis, of the Caprine beta-globin gene cluster in
      Norwegian dairy goats.
AB  - Restriction fragment length polymorphism analysis has been used to characterize
      the beta-globin cluster in Norwegian dairy goats. Several polymorphic Taq I
      restriction sites were identified by double digestions with Bam HI, Hind III, and
      Eco RI, and restriction maps of the different beta C, beta A and beta F alleles
      were established. Allelic association between the previously established beta
      globin types at the protein level and specific Taq I alleles was found.
      Furthermore, a preferential association between certain RFLP haplotypes and beta
      globin types was observed.

PMID- 1974545
TI  - Respiratory-burst stimulants desensitize beta-2 adrenoceptors on human
      polymorphonuclear leukocytes.
AB  - We investigated the effect of respiratory-burst stimulants on beta-2
      adrenoceptors in human polymorphonuclear leukocytes (PMNL). Pre-incubation of
      PMNL with these substances did not affect the number or affinity of the receptors
      but desensitized them, as shown by the "right-shift" in (-)-isoproterenol
      competition isotherms. H-7, an established protein kinase C inhibitor, and
      nimesulide, a new putative inhibitor of this enzyme, blunted both superoxide
      anion production and beta-2 adrenoceptor desensitization. A positive correlation
      was found between superoxide anion generation and the "right-shift" in
      isoproterenol competition isotherm (r = 0.92; p less than 0.01). Desensitization
      of beta-2 adrenoceptors was not due to superoxide anions per se since incubation
      of PMNL with superoxide anion scavengers (superoxide dismutase and catalase) did
      not modify the results.

PMID- 1974547
TI  - Identification and characterization of a beta-adrenergic receptor in hamster
      Sertoli cells.
AB  - Sertoli cells cultured from immature hamsters contain a beta-adrenergic receptor
      which is coupled to the cAMP second messenger system. Thus, isoproterenol,
      epinephrine, and norepinephrine, which act via beta-adrenergic receptors, all
      stimulate cAMP accumulation in Sertoli cells cultured for 4-5 days. This cAMP
      response to isoproterenol is inhibited stereospecifically by the beta-receptor
      blocker, propranolol. It is also sensitive to inhibition by beta-adrenergic
      antagonists in this order of potency: nonspecific beta receptor antagonists,
      propranolol, timolol, hydroxypindolol greater than beta 1 selective antagonists,
      oxyprenolol, metoprolol much much greater than beta 2 selective antagonist,
      butoxamine. Butoxamine was at least 1000-fold less sensitive than either the
      nonspecific or the beta 1 selective antagonists at inhibiting the response of
      either isoproterenol (nonspecific), dobutamine (beta 1 selective) or zinterol
      (beta 2 selective). The hamster Sertoli cell beta receptor is, therefore,
      predominantly of the B1 subtype. This beta receptor mediated increase in cAMP is
      sensitive to homologous desensitization and is stimulated synergistically by
      forskolin. In addition, Seroli cells freshly isolated from immature hamsters
      contain an active beta receptor. However, this beta receptor mediated increase in
      cAMP is dependent on the type of trypsin used in the cell preparation. In
      agreement with Kierszenbaum et al (1985), freshly isolated Sertoli cells from
      immature rats never responded to the catecholamines regardless of the type of
      trypsin used; indicating an important physiologic difference between rat and
      hamster Sertoli cells.

PMID- 1974548
TI  - Decreased insulin binding to porcine adipocytes in vitro by beta-adrenergic
      agonists.
AB  - The present study was conducted to determine the influence of dibutyryl-cAMP
      (dbcAMP), epinephrine, ractopamine and clenbuterol on insulin binding to porcine
      adipocytes. Dibutyryl-cAMP decreased insulin binding to swine adipocytes by 40
      and 20% at 1.8 and 25.8 ng insulin/ml, respectively. Ractopamine and clenbuterol
      directly reduced insulin binding at the low insulin concentration and decreased
      binding at high insulin concentrations in the presence of adenosine deaminase.
      Scatchard analysis suggested that the reduction of insulin binding was due to a
      decrease in receptor number. Epinephrine alone did not influence insulin binding.
      In the presence of theophylline, epinephrine decreased binding at both low and
      high insulin concentrations; however, ractopamine plus theophylline decreased
      binding only at the low insulin concentration. Clenbuterol did not affect insulin
      binding in the presence of theophylline. Propranolol blocked the inhibitory
      effect of epinephrine on insulin binding. These beta-adrenergic agonists can
      inhibit insulin binding and, thus, antagonize insulin action in swine adipocytes.

PMID- 1974549
TI  - Alterations in postmortem degradation of myofibrillar proteins in muscle of lambs
      fed a beta-adrenergic agonist.
AB  - Dietary administration of 4 ppm of the beta-agonist L-644,969 (Merck Sharpe and
      Dohme Research Laboratories) to finishing lambs induced a decrease (10 to 14%, P
      less than .05) in extractable calpain I activity in the longissimus muscle (LD)
      at death (d 0). At 4 d postmortem (d 4), extractable calpain I levels in the LD
      of both control and treated lambs were reduced (P less than .001) from those
      present at d 0, but the extractable activity in the LD was reduced to a greater
      extent in control than in treated lambs. Calpain II activity was increased 42% (P
      less than .005) in LD of treated lambs; however, no significant differences were
      observed between d 0 and d 4 calpain II activity within treated or control LD
      samples (P greater than .1). Calpastatin activity was higher in the LD of treated
      lambs (74% on d 0, P less than .001 and 430% on d 4, P less than .001) than in
      the LD of control lambs. Measurable cathepsin B activity was decreased (29% on d
      0, P less than .05) and measurable cathepsin H activity was increased (10% on d
      0, P less than .05 and 10% on d 4, P less than .05) in the LD of treated lambs
      compared with controls. On d 2, 4 and 6 postmortem, degradation in myofibrils
      isolated from the LD was lower for treated than for control lambs. Warner
      Bratzler shear values for loin chops from treated lambs were higher on both d 3
      (111%) and 6 (108%) postmortem than for chops from control lambs (P less than
      .001). L-644,969-induced decreases in muscle proteolytic capacity may limit
      postmortem myofibril degradation and contribute to the reduced tenderness
      observed. This decreased proteolytic capacity may contribute to increased
      muscularity of L-644,969-treated lambs.

PMID- 1974550
TI  - Stimulation of tracheal ciliary beat frequency by capsaicin.
AB  - To determine the possible involvement of neural and cyclooxygenase pathways
      whereby irritants might affect cilia activity in vivo, the temporal response of
      canine tracheal ciliary beat frequency (CBF) to the inhaled surrogate irritant
      capsaicin was studied. CBF was measured on the ventral midtracheal surface of
      barbiturate-anesthetized eucapnically ventilated beagle dogs by heterodyne-mode
      laser light scattering. After base-line CBF was established, hexamethonium
      bromide (2 mg/kg iv), ipratropium bromide (0.5 microgram/kg iv), indomethacin (2
      mg/kg iv), or intravenous 0.9% saline was administered. Aerosolized 3 Z 10(-9) M
      capsaicin in 0.9% saline was delivered for 2 min, and CBF was measured for the
      following 60 min. Control experiments used 0.9% saline sham aerosol with a 0.9%
      saline sham block. Aerosolized capsaicin stimulated CBF from a base line of 6.2
      +/- 1.4 (SD) Hz (n = 230) to a mean maximum of 17.7 +/- 7.3 Hz (n = 16) 23 min
      after aerosol delivery, and CBF returned to base line within 60 min. Neither
      hexamethonium bromide, ipratropium bromide, nor indomethacin changed CBF from
      base-line values. The episodic CBF stimulatory response to capsaicin after
      commencement of aerosol was completely inhibited by hexamethonium bromide.
      Ipratropium bromide partially inhibited the first 15 min and totally inhibited
      the following 45 min of stimulatory response. Indomethacin inhibited the initial
      15 min but had less effect on the following 45 min of stimulatory response. These
      data indicate that multiple stimulatory mechanisms function over a prolonged
      period of time to affect the removal of irritants from the airways and that these
      mechanisms differ from those involved in the maintenance of basal CBF.

PMID- 1974551
TI  - Keratinocyte transglutaminase in human skin and oral mucosa: cytoplasmic
      localization and uncoupling of differentiation markers.
AB  - Expression of keratinocyte transglutaminase, a specific differentiation marker,
      has been examined by immunogold-silver cytochemistry in human epidermis and oral
      epithelium, and in oral mucosal hyperplasia and neoplasia. Two major findings
      have been obtained. First, considerable immunoreactivity was evident not only at
      the plasma membrane (the site of cross-linked envelope formation) but also in the
      cytoplasm of spinous cells, suggesting a cytoplasmic function for this
      transglutaminase. Staining at the cell border was seen principally in the
      granular layer of orthokeratinized epithelium (epidermis, hard palate), the outer
      spinous cells of ortho- and parakeratinized epithelium and in the suprabasal
      cells showing squamous differentiation in benign and malignant neoplasms. By
      contrast, diffuse cytoplasmic staining was observed in the upper spinous layer of
      the normal epithelium and benign lesions. The cytoplasmic immunoreactivity, which
      extended nearly to the basal layer in hyperkeratosis of the oral mucosa, was
      evident in two of three verrucous carcinomas examined. In keeping with their
      undifferentiated character, invasive nests of squamous cell carcinoma and
      basaloid epithelium in benign and neoplastic lesions were immunonegative for
      transglutaminase. The second major finding was that lesions of severe oral
      epithelial dysplasia, immunonegative for transglutaminase, were capable of
      expressing involucrin immunoreactivity, indicating an uncoupling of keratinocyte
      programming. These results suggest that immunogold-silver staining for
      transglutaminase may be useful in evaluating the degree of differentiation in
      benign and malignant oral epithelial proliferation.

PMID- 1974552
TI  - Reversed-phase liquid chromatographic method with amperometric detection for the
      determination of the dopamine agonist 2-(N-propyl-N-2-thienylethylamino)-5
      hydroxytetralin (N-0437) in human plasma and urine.

PMID- 1974553
TI  - HLA antigens in Japanese patients with myasthenia gravis.
AB  - HLA antigens in 104 Japanese patients and 41 families with myasthenia gravis (MG)
      were investigated. The frequencies of DR9 and DRw13 were significantly increased
      in the patients who developed MG before 3 yr of age. The DQw3 antigen was
      positive for all the patients that developed MG before 15 yr with only one
      exception. All the examined cases that developed MG before 3 yr (including this
      DQw3 negative patient) had the same DQA and DQB DNA restriction fragments. These
      HLA frequencies decreased as the age of onset increased, and no significant
      association was observed in adult-onset MG. No patients had B8, DR3, and DQw2.
      The relative risk was higher for the DR9/DRw13 heterozygotes (37.4) than for DR9
      (16.4) or DRw13 (7.1) in the childhood-onset MG. Statistical analysis suggested
      that DR9 and DRw13 (or DQw1 and DQw3) act synergistically in the disease
      development. Family study revealed diverse DR9 haplotypes. The most frequent
      DRw13 haplotype was Bw44-BFF-C4A3B1-DRw13-DQw1, which may be evolutionarily
      related to the caucasian B8-DR3-DQw2 haplotype. These results showed that MG in
      early childhood in Japanese individuals is genetically different from that in
      adulthood and that in caucasians.

PMID- 1974556
TI  - Proctolin in the innervation of the locust mandibular closer muscle modulates
      contractions through the elevation of inositol trisphosphate.
AB  - Extracts of the locust (Locusta migratoria) mandibular closer muscle separated on
      reverse-phase HPLC and tested for bio-activity on the locust oviduct contain a
      bio-active substance that coelutes with authentic proctolin. Furthermore, the
      effect on oviduct contractions of this compound is indistinguishable from that of
      authentic proctolin. Antiserum to proctolin stains numerous axons with beaded
      endings that run along the fibres of the closer muscles and, in addition, the
      antiserum stains a number of cell bodies in the suboesophageal ganglion, some of
      which have axons in the mandibular nerve that innervates the mandibular
      musculature. The function of proctolin appears to be modulatory as its presence
      significantly increases the amplitude of neurally evoked contractions of the
      closer muscle. This effect can be mimicked by the addition of inositol 1,4,5
      trisphosphate (IP3) to preparations in which the muscles have been permeabilized
      with dimethyl sulfoxide. The involvement of this second messenger is further
      implicated as we also show that proctolin produces a large, significant increase
      in the IP3 content of homogenized muscle.

PMID- 1974557
TI  - Development of neuropeptide Y (NPY) immunoreactive neurons in the rat occipital
      cortex: a combined immunohistochemical-autoradiographic study.
AB  - The postnatal development of neuropeptide Y (NPY)-immunoreactive neurons,
      previously labeled with [3H]thymidine on embryonic days E14-E21, has been studied
      in the rat occipital cortex. Immunohistochemistry combined with autoradiography
      showed evidence of a modified "inside-out" pattern of maturation. NPY-neurons are
      generated between E14 and E20 and are found in layers II-VI of the cortex and the
      subcortical white matter. NPY neurons from all these birthdates are overproduced
      at first, although cells generated at E16 produce the greatest excess, followed
      by E15 and E17. Some of these transient neurons are found in the "wrong" layer
      for their birthdates, and their elimination produces a more "correct" alignment
      at maturity. However, most of the NPY neurons that survive are generated at E17,
      and these cells are found throughout layers II-VI with a preponderance in layer
      VI. This evidence is strongly suggestive of cell death rather than merely
      cessation of production of NPY.

PMID- 1974554
TI  - Paradoxical expression of adenosine deaminase in T cells cultured from a patient
      with adenosine deaminase deficiency and combine immunodeficiency.
AB  - T lymphocytes cultured from a patient (T.D.) with adenosine deaminase (ADA)
      deficiency expressed ADA activity in the normal range, inconsistent with her
      severe immunodeficiency, metabolic abnormalities, and with the absence of ADA
      activity in her B lymphocytes and other nucleated hematopoietic cells. ADA from
      T.D. T cells had normal Km, heat stability, and sensitivity to ADA inhibitors.
      Examination of HLA phenotype and polymorphic DNA loci indicated that T.D. was
      neither chimeric nor a genetic mosaic. Amplified and subcloned ADA cDNA from ADA+
      T.D. T cells was shown by allele-specific oligonucleotide hybridization to
      possess the same mutations (Arg101----Trp, Arg211----His) previously found in the
      ADA-T.D. B cell line GM 2606 (Akeson, A. L., D. A. Wiginton, M. R. Dusing, J. C.
      States, and J. J. Hutton. 1988. J. Biol. Chem. 263:16291-16296). Our findings
      suggest that one of these mutant alleles can be expressed selectively in IL-2
      dependent T cells as stable, active enzyme. Cultured T cells from other patients
      with the Arg211----His mutation did not express significant ADA activity, while
      some B cell lines from a patient with an Arg101----Gln mutation have been found
      to express normal ADA activity. We speculate that Arg101 may be at a site that
      determines degradation of ADA by a protease that is under negative control by IL
      2 in T cells, and is variably expressed in B cells. Il-2 might increase ADA
      expression in T cells of patients who possess mutations of Arg101.

PMID- 1974558
TI  - Localization of chromogranins, non-neuron-specific enolase, and different forms
      of somatostatins in the submandibular salivary glands of mice.
AB  - The localizations of chromogranins A, B, and C, neuron-specific enolase (NSE,
      gamma gamma-type) and non-NSE (alpha alpha-type), and different forms of
      somatostatins were immunocytochemically identified. The localizations were
      compared with those of epidermal growth factor (EGF) and nerve growth factor
      (NGF) in the submandibular salivary glands (SMG) of male mice at five to six
      weeks of age, with use of a variety of antibodies and the peroxidase
      antiperoxidase (PAP) and avidin-biotin complex (ABC) detection methods. In the
      SMG of male mice, the major chromogranin present was chromogranin A, whereas
      chromogranins B and C were not detected at these ages by either method.
      Chromogranin A-like immunoreactivity was located in the granular convoluted
      tubule (GCT) cells of the SMG, whereas non-NSE immunoreactivity was observed
      throughout the duct system and in some acinar-associated cells. NSE was not
      detected in any part of the SMG. The distribution of chromogranin A and
      somatostatins in the GCT cells was similar to that of EGF and NGF. Our results
      strongly suggest that chromogranin A and somatostatins, but not chromogranin B or
      C, may be useful as a means of differentiation of the cells in the duct system of
      the SMG responsible for the production of biologically-active factors.

PMID- 1974555
TI  - HLA-DQ gene complementation and other histocompatibility relationships in man
      with the anti-Ro/SSA autoantibody response of systemic lupus erythematosus.
AB  - A strong gene interaction between HLA-DQ1 and DQ2 alleles has been associated
      with anti-Ro/SSA autoantibodies (Harley, J.B., M. Reichlin, F. C. Arnett, E. L.
      Alexander, W. B. Bias, and T. T. Provost. 1986. Science [Wash. DC]. 232:1145
      1147; Harley, J. B., A. S. Sestak, L. G. Willis, S. M. Fu, J. A. Hansen, and M.
      Reichlin. 1989. Arthritis Rheum. 32:826-836; Hamilton, R. G., J. B. Harley, W. B.
      Bias, M. Roebber, M. Reichlin, M. C. Hochberg, and F. C. Arnett. 1988. Arthritis
      Rheum. 31:496-505). To test a gene complementation mechanism for these results,
      restriction fragment length polymorphisms (RFLP) of the DQ alpha and DQ beta
      genes have been related to Ro/SSA precipitins in patients with systemic lupus
      erythematosus. In this study Ro/SSA precipitins are related to the simultaneous
      presence of a particular pair of RFLPs. A DQ alpha RFLP associated with HLA-DQ1
      and a DQ beta RFLP associated with HLA-DQ2 predict that the alpha beta
      heterodimer in HLA-DQ1/DQ2 heteroxygotes is most closely related to anti-Ro/SSA
      autoantibodies, thereby supporting a gene complementation mechanism. Beyond this
      effect, an RFLP associated with HLA-DQ2 and/or DR7 is also related to Ro/SSA
      precipitins. Multiple molecular histocompatibility mechanisms are implicated,
      therefore, in the production of anti-Ro/SSA autoantibodies in autoimmune disease.
      For anti-Ro/SSA autoantibodies in SLE, and perhaps more generally, these data
      show that the histocompatibility antigens are among the elements that confer
      autoimmune response specificity and restrict the production of particular
      autoantibodies among patients with systemic lupus erythematosus.

PMID- 1974559
TI  - An HLA-associated nonresponsiveness to mellitin: a component of bee venom.
AB  - Previous work has demonstrated a close association between certain
      histocompatibility antigens and the gene that controls the IgE response to
      certain ragweed allergens. For example, there is a 90% association between IgE
      production to the short ragweed allergen, Amb a V, and an HLA class II allele. To
      assess whether these HLA linkages are specific for ragweed, we have investigated
      the association between HLA antigens and the capacity of individuals to mount a
      specific IgE response to melittin in patients with bee-venom allergy. Twenty-two
      subjects with bee-venom sensitivity, 22 healthy beekeepers without bee-venom
      allergy, and a normal population of 149 unselected individuals were studied. With
      serologic tissue typing and restriction fragment length polymorphism analysis, we
      have demonstrated a significant decrease in the HLA-DR4 and DQw3 alleles in
      subjects who are allergic to melittin compared to the control populations. There
      was also a negative association between the presence of HLA-DR4 and DQw3 alleles
      with the capacity of the individuals to mount an IgE response to phospholipase A2
      (PLA2). The bee-venom sensitive subjects had a slightly lower titer of anti-PLA2
      IgG when these subjects were compared to the bee-venom insensitive beekeepers.
      These results support the view that either HLA-DR or HLA-DQ has a protective role
      in controlling the IgE immune response. Lack of an IgE response to melittin or
      PLA2 is unlikely to be due to a failure to recognize allergen.

PMID- 1974560
TI  - Effects of azelastine on vagal neuroeffector transmission in canine and human
      airway smooth muscle.
AB  - Azelastine is a newly developed antiallergic drug that is reported to antagonize
      histamine and leukotrienes in addition to its inhibitory action on release of
      chemical mediators. In the present study, the effects of azelastine on
      neuroeffector transmission in the airway smooth muscles with double sucrose gap
      and isometric tension-recording methods were evaluated. Azelastine (10(-8) to 10(
      6) mol/L) markedly decreased the contractile response of human bronchial and dog
      tracheal muscle strips to electrical field stimulation (10 pulses at 20 V, 20 Hz,
      800 microseconds) in a dose-dependent manner. In parallel with actions on twitch
      contractions, azelastine suppressed the amplitude of excitatory junction
      potentials of dog trachea without changing the resting membrane potential and
      input resistance of smooth muscle cells. However, azelastine did not alter
      acetylcholine sensitivity of the smooth muscle cells. These results indicate that
      azelastine possesses an inhibitory action on the release of acetylcholine by
      vagal nerve terminals. This inhibitory effect of azelastine may contribute to the
      treatment of asthma in addition to its antiallergic actions.

PMID- 1974561
TI  - Lack of subsensitivity to loratadine during long-term dosing during 12 weeks.
AB  - The development of subsensitivity to first-generation H1 blockers often occurs
      within days or weeks of treatment. It is manifested by a decrease in efficacy and
      a waning of the inhibition of skin reactivity to allergen or histamine.
      Subsensitivity to loratadine was investigated in a double-blind, placebo
      controlled parallel group study in 20 allergic subjects (22 to 35 years) who
      received either placebo or loratadine (10 mg one daily) for 12 weeks. Skin prick
      tests were done with six threefold increasing concentrations of standardized
      allergen extracts (orchard grass or mite) and histamine-coated Phazet. Skin tests
      were done before any treatment and after 7, 28, 56, and 84 days. Wheals and
      flares were measured. Compliance was monitored strictly during the study.
      Statistical analysis was done by parallel line bioassay and Wilcoxon W test. Skin
      test reactivity to histamine or allergen did not change throughout the trial in
      the placebo-treated group. Patients treated by loratadine had a significantly
      smaller wheal-and-flare reaction after 7 days. This effect was greater at 28 days
      and lasted throughout the treatment period. This study demonstrates that
      subsensitivity to loratadine measured by histamine and allergen skin tests does
      not develop during a 12-week period.

PMID- 1974562
TI  - Differences in the expression profiles of CD45RB, Pgp-1, and 3G11 membrane
      antigens and in the patterns of lymphokine secretion by splenic CD4+ T cells from
      young and aged mice.
AB  - Previous studies indicate that the 3G11, CD45RB, and Pgp-1 determinants are
      differentially expressed on CD4+ T cell subsets in the mouse. We used multicolor
      immunofluorescence staining and flow cytofluorometric analysis to examine the
      expression of each of these determinants on splenic CD4+ cells from young (age 3
      to 6 mo) and aged (age 24 to 26 mo) C57BL/6 mice. The CD4+ pool from aged mice
      contained significantly reduced numbers of 3G11+ and CD45RBhi cells, but
      increased numbers of Pgp-1hi cells, in comparison with the young group. Analysis
      of the simultaneous expression of all three subset determinants on CD4+ cells
      revealed that, in young mice, the major fraction (greater than 50%) was
      3G11+CD45RBhiPgp-1lo. Among the less prevalent cell phenotypes, reductions in
      3G11 expression correlated with decreases in CD45RB levels and increases in Pgp-1
      levels. The phenotype that dominated the young group (3G11+CD45RBhiPgp-1lo) was
      approximately fivefold less represented in the aged group. The CD4+ pool from
      aged mice was characterized by increases in the 3G11-CD45RBvariablePgp-1hi and
      the 3G11+CD45RBloPgp-1hi phenotypes. To evaluate possible age-associated
      differences in cytokine secretion patterns by splenic CD4+ cells, purified CD4+
      cells from each age group were stimulated in vitro with immobilized anti-CD3
      epsilon mAb and accessory cells. At various times thereafter, supernatants from
      cultures were tested for IL-2 and IL-4 content by using the CTLL.6 and 11.6
      bioassays, respectively, and the CD4+ cells were assayed for [3H]TdR uptake. Cell
      cultures from the aged group exhibited similar peak IL-2 accumulation and lower
      peak [3H]TdR uptake, but greatly increased peak IL-4 accumulation, as compared
      with cell cultures from the young group. The expression patterns of subset
      determinants, in conjunction with cytokine secretion profiles, indicate that, in
      aged mice, marked alterations occur in the subset composition of the splenic CD4+
      cell pool. These findings are discussed in the context of previous findings on
      changes in T cell reactivity with advancing donor age.

PMID- 1974563
TI  - CD27 induction on thymocytes.
AB  - CD27 mAb recognize a disulfide-linked homodimer of 55 kDa present in the majority
      of T cells and in a minor subpopulation of thymocytes. Although an increase of
      CD27 expression has been described in activated T cells, this Ag is poorly
      expressed in long term growing T cells. It has been also reported that CD27-
      becomes CD27+ upon activation. In the aim to better know the relationship between
      CD27 expression and the activation and maturation processes, the induction of
      this Ag in thymocytes was analyzed. The results obtained in this work show that:
      1) CD27 is expressed only in thymocytes with high CD3 Ag density. 2) Its
      expression can be induced in low density CD3 CD4+ CD8+ cells by Con A and in low
      CD3 Ag density by PMA+ionomycin. 3) PMA alone or in combination with rIL-2
      induces CD25 and CD71 expression but not CD27. 4) Unlike CD27, the Ag CD45RA,
      CD26, and CD76, which are present only in a minor thymocyte subpopulation, are
      not induced in double positive thymocytes. Because it has been reported that
      cyclosporin A interferes with thymocytes maturation and blocks the transition
      from double to single positive cells, its effect was measured on CD27 induction.
      Cyclosporin A did not inhibit CD25 expression induced by both Con A and
      PMA+ionomycin, but under these conditions it inhibited the induction of CD27. In
      this paper we discuss whether CD27 could be implicated in T cell maturation.

PMID- 1974565
TI  - A peripheral mechanism preserves self-tolerance to a secreted protein in
      transgenic mice.
AB  - We have examined mechanisms of tolerance to circulating self-proteins in mice
      that are transgenic for human insulin. Normal, nontransgenic mice develop serum
      antibody responses when injected with human insulin in CFA; syngeneic transgenic
      mice do not. B cell responsiveness was assessed by immunizing with human insulin
      coupled to a T-independent Ag, Brucella abortus. No differences were found in the
      numbers of insulin-specific splenic plaque-forming cells between transgenic and
      nontransgenic mice suggesting that insulin-specific B cells are not tolerant in
      transgenic mice. Similarly, APC from transgenic and nontransgenic mice display no
      differences in their ability to process and present human insulin to human
      insulin-specific T cells in vitro. However, marked differences were detected
      between transgenic and nontransgenic T cells. Lymph node T cells from transgenic
      mice primed with human insulin provided no detectable helper activity for
      secondary antibody responses to human insulin whereas, lymph node T cells from
      nontransgenic mice did. Nevertheless, lymph node T cells from transgenic mice
      developed significant proliferative responses to human insulin. Lymph node T
      cells obtained from transgenic and nontransgenic mice were fused to BW5147 and
      human insulin-specific T cell hybridomas were generated. The fact that human
      insulin-specific T cell hybridomas were obtained from the transgenic mice
      suggests that these T cells were not clonally deleted. In addition, APC from
      transgenic mice did not stimulate human insulin-specific hybridomas from normal
      mice in the absence of exogenous insulin. We suggest that T cells specific for
      human insulin are not deleted in the thymus of transgenic mice because APC in the
      thymus do not bear the requisite levels of endogenous human insulin/Ia complexes.
      Therefore, we conclude that tolerance in the transgenic mice is preserved by
      peripheral mechanisms.

PMID- 1974564
TI  - IL-2 protects against anti-CD3-induced cell death in human medullary thymocytes.
AB  - In recent years, several studies have confirmed the clonal elimination of
      thymocytes with receptors that recognize Ag and MHC molecules present on the
      membrane of thymic stromal cells, a process that may be relevant to the
      establishment of self-tolerance. In our work, we show that anti-CD3 treatment of
      single positive CD4+ or CD8+ human medullary thymocytes (obtained by anti-CD1a
      plus C) induces their apoptotic death. Some events commonly associated with the
      early steps of normal activation (IL-2R expression, increase in cytoplasmic Ca2+)
      are also induced after anti-CD3 treatment. Nevertheless, IL-2 is not secreted by
      these activated cells. The addition of exogenous IL-2 inhibits the apoptosis
      induced by anti-CD3. We suggest that the lack of secretion of IL-2 by medullary
      thymocytes may be a physiologic mechanism implicated in the process of negative
      selection that leads to tolerance.

PMID- 1974566
TI  - Deviations in thymocyte development induced by divalent and monovalent ligation
      of the alpha/beta T cell receptor and by its cross-linking to CD8.
AB  - Fetal thymic organ cultures (FTOC) were tested as a model system to induce, in a
      polyclonal fashion, negative and positive thymic selection events. By flow
      cytometry, thymocytes developed in FTOC differed in several parameters from their
      in vivo differentiated counterparts. In particular, no clear distinction was
      possible between CD4+CD8+ immature cells with low TCR expression and mature CD4+
      or CD8+ cells with high TCR expression. Thymocyte development in FTOC was
      manipulated with three different antibody reagents: anti-V beta 8 (F23.1), anti
      Lyt-2.2 (19/178) and the quadroma derived bifunctional antibody HPHT-2, carrying
      one binding site of each. This antibody served also as a monovalent anti-V beta 8
      reagent in FTOC from Lyt-2.1 mouse strains. Antibody 19/178 suppressed the
      development of single positive CD8+ cells, but only at very high concentrations.
      F23.1 and HPHT-2 suppressed the development of CD4+V beta 8+ and CD8+V beta 8+
      thymocytes at relatively low concentrations giving rise to V beta 8 occupancies
      from about 2% upwards. Suppression was equally pronounced in cells with low and
      high TCR densities. Moreover, V beta 8 suppression occurred upon divalent and
      monovalent V beta 8 binding and was not significantly influenced by V beta 8-CD8
      cross-linking. This suggests that ligation of the TCR alone is sufficient for
      clonal deletion. The data do not exclude a role for CD8 as an accessory adhesion
      molecule but suggest that exogenous cross-linking of CD8 to the TCR is not
      essential in transmembrane signaling for clonal deletion. At lower antibody
      concentrations giving rise to V beta 8 occupancies below detection, V beta 8-CD8
      cross-linking by HPHT-2, but no divalent and monovalent V beta 8 ligation,
      induced an increase of CD8+V beta 8+ cells at the expense of CD4+ V beta 8+ cells
      with no change in the proportion of total V beta 8+ thymocytes. The latter effect
      was quantitatively of borderline significance but reproducible. These latter
      results are compatible with the hypothesis that cross-linking of the alpha beta
      TCR and CD8 on the thymocyte surface provides a maturation signal resulting in
      loss of CD4 from CD4+ CD8+ double positive immature thymocytes.

PMID- 1974567
TI  - BP-1/6C3 expression defines a differentiation stage of transformed pre-B cells
      and is not related to malignant potential.
AB  - BP-1 antibody recognizes a cell surface molecule related to the zinc-dependent
      metallopeptidases that is expressed during a narrow window early in B cell
      differentiation. Expression of the same molecule, as originally recognized by the
      mAb 6C3, is widely accepted to be associated with the complete malignant
      transformation of pre-B lymphoid cells. We have examined BP-1/6C3 expression in a
      panel of established Abelson virus-transformed cells that includes both cells
      analogous to pre-B cells and to less differentiated B lineage cells that have not
      yet completed Ig H chain gene rearrangement. This analysis reveals that many of
      the less differentiated transformants do not express BP-1/6C3 for an extended
      culture period. In contrast, virtually all transformants that are analogous to
      normal pre-B cells express the determinant early in their culture history. The BP
      1/6C3 negative transformants are fully tumorigenic in syngeneic mice,
      demonstrating that BP-1/6C3 expression is not required for complete malignant
      transformation. Our data thus suggest that the pattern of BP-1/6C3 expression in
      Abelson virus-transformed cells mimics that observed in normal cells and is
      indicative of a differentiation event unrelated to the malignant potential of the
      cells.

PMID- 1974568
TI  - Identification of a new V kappa gene family that is highly expressed in
      hybridomas from an autoimmune mouse strain.
AB  - We have identified a new murine V kappa family that contains five to seven
      members, one member of which encodes the L chain V region of an anti-dsDNA
      antibody produced by a BALB/c hybridoma, C8.5. The cloned C8.5 V kappa gene
      exhibits highest homology with a human V kappa gene that was cloned from a
      nonproductive rearrangement but has never been seen in an expressed repertoire.
      Because this family was first identified in an autoantibody, we studied its
      expression in an autoimmune mouse strain. This V kappa family is expressed in 20%
      of hybridomas from NZB mice.

PMID- 1974569
TI  - Long-term survival of adoptively transferred tumor-infiltrating lymphocytes in
      mice.
AB  - We examined the long term survival of adoptively transferred, cultured tumor
      infiltrating lymphocytes (TIL) in sublethally irradiated nontumor-bearing mice.
      TIL were produced by culturing Thy-1-enriched single cell suspensions from a
      variety of murine tumors in exogenous IL-2 along with irradiated tumor cells and
      splenocytes. TIL were adoptively transferred i.v. to mice and such animals
      demonstrated a statistically significant degree of protection from a subsequent
      i.v. tumor challenge. This protection lasted up to 6 wk and occurred in the
      absence of exogenous IL-2 administration in vivo. Using congenic B6.PL Thy-1
      alpha/CY mice we demonstrated directly that TIL can survive in vivo for up to 6
      wk and that the adoptively transferred TIL were the source of the relative
      immunity to subsequent tumor challenge. We conclude that TIL contain cells with
      substantial functional longevity in vivo even in the absence of exogenous IL-2.
      These studies are relevant to ongoing clinical trials of TIL as a therapy for
      patients with advanced cancer.

PMID- 1974571
TI  - Interaction of copper(I) with nucleic acids.
AB  - Poly(dG-dC) and poly(I) form particularly stable complexes with Cu(I): thus
      characteristic UV absorbance changes enabled demonstration of Cu(I) transfer from
      poly(dA-dT) to poly(dG-dC), or from DNA to poly(I). Using pulse radiolysis to
      generate Cu(I), a rate constant of approximately 4 x 10(7) dm3 mol-1 s-1 (per
      base unit) was estimated for association of Cu(I) to native DNA, and slightly
      higher values were found for poly(dA-dT), poly(C), poly(dG-dC) and poly(G). For
      native DNA and for the models poly(dA-dT) and poly(dG-dC) the addition of Cu(I)
      was followed by secondary absorbance changes in the time scale of 10 ms, probably
      due to internal Cu(I) transfer; such secondary reactions were not detectable in
      heat-denatured DNA or in the homopolymers of A, C, G, and I. Extraction of Cu(I)
      from the DNA by EDTA is slow, 0.019 s-1, and independent of EDTA concentration,
      indicating that dissociation of the DNA-Cu(I) complex is the rate-determining
      step. A tentative value can hence be given for the DNA-Cu(I) stability constant:
      K = k (forward)/k (reverse) approximately 2 x 10(9) dm3 mol-1. Addition of H2O2
      to solutions of gamma-radiolytically generated DNA-Cu(I), at Cu(I)/base less than
      0.01, resulted in DNA degradation, comparable in yield to .OH-induced
      degradation. In the case of poly(dA-dT) and poly(dG-dC) the reaction of H2O2 with
      the corresponding Cu(I) complexes produced even more damage than the reaction of
      .OH. The formation of DNA-Cu(I), and the deleterious reaction with H2O2, were
      hardly affected by RNase or BSA, when added at equal (w/v) concentration.
      Dismutation of O2.- by (Cu,Zn)-SOD was partly inhibited by DNA and even more by
      poly(I) at pH 4.4, but not at pH 7, probably by competitive complexation of
      Cu(I), occurring in the catalytic cycle of SOD.

PMID- 1974570
TI  - UM4D4+ (CDw60) T cells are compartmentalized into psoriatic skin and release
      lymphokines that induce a keratinocyte phenotype expressed in psoriatic lesions.
AB  - UM4D4 (CDw60), the surface molecule of a novel antigen-independent T-cell
      activation pathway, was found to be highly expressed on lesional psoriatic T
      cells. To examine whether UM4D4 represents a T-cell activation pathway for
      psoriatic T cells, a T-cell line was initiated from an acute skin lesion and
      cloned by limiting dilution. Clonality was verified by analysis of T-cell
      receptor gene rearrangement. All T-cell clones tested, whether CD4+2H4+CD8-,
      CD4+2H4-CD8-, or CD4-CD8+CD11b-, expressed UM4D4 and were activated by the
      monoclonal antibody anti-UM4D4. Lesional psoriatic T-cell clones were
      heterogeneous in the degree of anti-UM4D4-induced proliferation and in their
      production of IL-2 and gamma-interferon. Lymphokines released by anti-UM4D4
      activation were capable of inducing ICAM-1 and HLA-DR expression on cultured
      normal keratinocytes. Thus, the high expression of UM4D4 on T-cells in psoriatic
      skin provides an alternative mechanism for T-cell activation that may be
      operative in the psoriatic lesional milieu. Indeed, activation of lesional T
      cells through the UM4D4 molecule resulted in release of lymphokines that directly
      induced keratinocytes to express a phenotype displayed in psoriatic skin lesions.

PMID- 1974572
TI  - The fate of DNA-protein crosslinks formed in gamma-irradiated metaphase cells.
AB  - The induction of DNA-protein crosslinks (DPC) was compared in gamma-irradiated
      metaphase and asynchronous Chinese hamster V79 cells. Unirradiated metaphase
      cells were found to have a higher level of background DPC than unirradiated
      asynchronous cells, and the metaphase cells were less susceptible to radiation
      induced DPC production than were asynchronous cells. SDS-PAGE analysis of
      crosslinked proteins prepared from the two cell populations, both irradiated and
      unirradiated, showed very similar protein patterns. Crosslinked DNA was isolated
      and probed with radioactively labelled interphase poly(A+)RNA. The results
      indicated that the hypersensitivity of interphase actively transcribing DNA
      sequences to radiation-induced DPC formation was maintained at metaphase when the
      chromosomes are highly condensed. In contrast to asynchronous cells, radiation
      induced DPC formed in metaphase cells were not removed during a 4 h post
      irradiation period. However, metaphase cells appear to be able to remove the
      active DNA involved in DPC as indicated by a depletion of the probed sequences in
      the unrepaired DPC. Cell size analysis as well as cytological examination of the
      irradiated metaphase cells showed an absence of cell division during post
      irradiation incubation. Furthermore, about 50% of the irradiated metaphase cells
      grew into giant cells which contain multiple nuclei and micronuclei, an
      indication of aberrant chromosome segregation.

PMID- 1974573
TI  - Calibration of pulsed field gel electrophoresis for measurement of DNA double
      strand breaks.
AB  - The pulsed field gel electrophoresis (PFGE) assay was calibrated for the
      measurement of X-ray-induced DNA double-strand breaks in Chinese hamster ovary
      (CHO) cells. Calibration was conducted by incorporating [125I]deoxyuridine into
      DNA, which induces one double-strand break for every disintegration that occurs
      in frozen cells. Based on the percentage of the DNA migrating into the gel, the
      number of breaks/dalton/Gy was estimated to be (9.3 +/- 1.0) x 10(-12). This
      value is close to (10 to 12) x 10(-12) determined by neutral filter elution using
      similar cell lysis procedures at 24 degrees C and at pH 8.0. Also, the estimate
      is in good agreement with the value of (11.7 +/- 2) x 10(-12) breaks/dalton/Gy as
      measured in Ehrlich ascites tumour cells using the neutral sucrose gradient
      method (Blocher 1988), and (6 to 9) x 10(-12) breaks/dalton/Gy as measured in
      mouse L and Chinese hamster V79 cells using neutral filter elution (Radford and
      Hodgson 1985).

PMID- 1974574
TI  - The irradiation of V79 mammalian cells by protons with energies below 2 MeV. Part
      II. Measurement of oxygen enhancement ratios and DNA damage.
AB  - The effectiveness of low-energy (below 2 MeV) protons at inducing DNA damage in
      the form of single- and double-strand breaks has been determined. Protons with
      mean energies of 1.90 MeV, 1.15 MeV and 0.76 MeV corresponding to track average
      LETs of 17 keV/microns, 24 keV/microns and 32 keV/microns, respectively, have
      been used and compared with 250 kVp X-rays and 3.8 MeV 238Pu alpha-particles.
      Although there was variation in the RBE for DNA ssb induction with LET, the RBEs
      for dsb induction at all three proton energies and for 3.8 MeV alpha-particles
      were all around 1.0. This suggests that, if DNA dsb are important in radiation
      induced cell lethality, the probability of an induced dsb leading to a lethal
      event increases with increasing LET of radiation. Oxygen enhancement ratios were
      measured for both cell survival and DNA dsb induction, and in both cases a
      decrease in OER with increasing LET was observed.

PMID- 1974575
TI  - Recovery of human lymphocytes damaged with gamma-radiation or enzymatically
      produced oxygen radicals: different effects of poly(ADP-ribosyl)polymerase
      inhibitors.
AB  - Quiescent human lymphocytes were damaged in two different ways, both producing
      toxic oxygen radicals: xanthine oxidase plus hypoxanthine (XOD/HYP), or gamma
      rays. Under conditions where DNA synthesis was reduced to 10-20% of control,
      inhibitors of poly(ADP-ribosyl)polymerase (ADPRP, an enzyme that becomes
      activated in the presence of DNA strand breaks) allowed lymphocytes to recover
      completely when the damage was caused by XOD/HYP, but they did not affect DNA
      synthesis of irradiated cells. However, a protective effect of ADPRP inhibitors
      was observed with irradiated lymphocytes receiving doses greater than or equal to
      50 Gy. Unscheduled DNA synthesis was Unscheduled DNA synthesis was significantly
      increased when lymphocytes were damaged by high radiation doses in the presence
      of ADPRP inhibitors. We suggest that ionizing radiation does not stimulate
      poly(ADP-ribose) synthesis in lymphocytes at doses that impair lymphocyte DNA
      synthesis by 80-90%, while ADPRP may be involved in the repair of DNA lesions
      occurring at higher radiation doses.

PMID- 1974576
TI  - The relationship between colony-forming ability and chromosomal aberrations
      induced in human T-lymphocytes after gamma-irradiation.
AB  - Using aliquots from the same samples of irradiated normal human blood, T
      lymphocyte survival was measured by (a) 14-day colony growth, (b) the proportion
      of chromosomally normal first post-irradiation metaphases and (c) the proportion
      of cells not suffering interphase death and delay within 48 h after irradiation.
      Combining (b) and (c) gives a prediction of the proportion of cytogenetically
      undamaged cells which reach metaphase after 48 h. These cells should be capable
      of producing viable colonies under suitable culture conditions. A comparison of
      these values with those observed in (a) shows a reasonable agreement in
      accordance with the hypothesis that gross chromosomal damage and cell
      reproductive death are closely related.

PMID- 1974577
TI  - Use of the micronucleus assay for the selective detection of radiosensitivity in
      BUdR-unincorporated cells after pulse-labelling of exponentially growing tumour
      cells.
AB  - To determine the radiosensitivity of non-S-phase tumour cells in vitro, survival
      curves of SCC VII tumour cells were obtained after a short block with
      hydroxyurea. Dose-response curves of micronucleus (MN) frequency appearing in non
      S-phase cells were also determined by excluding S-phase cells with
      immunofluorescence staining to 5-bromo-2'-deoxyuridine (BUdR). Both the dose
      response curves of MN frequency and survival curves were analysed by a linear
      quadratic model (surviving fraction = exp (-alpha D-beta D2), MN frequency =
      aD+bD2+c). A good correlation between the alpha/beta and alpha/beta ratios was
      observed. In both BUdR-unincorporated and asynchronous cell cultures, the
      regression lines between the surviving fraction and micronucleus frequency were
      statistically identical. Therefore, it was shown that cell survival curves, which
      cannot be obtained directly by the routine colony-formation technique, can be
      calculated using the micronucleus frequency and the regression line in
      asynchronous cell cultures. Therefore, it should be possible to detect the
      response to irradiation of quiescent cells in tumours using the
      immunofluorescence staining to BUdR and the MN frequency assay.

PMID- 1974578
TI  - The evaluation of erythrocyte membrane response to combined treatment of
      radiation and nitroimidazoles.
AB  - The effect of gamma-irradiation on human erythrocytes in the presence of
      nitroimidazoles in aerobic conditions was investigated. It was found that both 1
      (2-nitroimidazole-1-y1)-3-methoxy-2-propanol (misonidazole, MISO) and 1-(2-methyl
      4,5-dinitroimidazoyle)-3-chloro-2-hydroxypropane (4,5-NO2) inhibited membrane
      bound ATPase activity without irradiation. Treatment with 4,5-NO2 enhanced the
      radiation-induced decrease in the activity, whereas irradiation after treatment
      of membranes with MISO had a variable, concentration-dependent effect.
      Irradiation of cells in the presence of MISO concentrations less than 34
      micrograms/ml decreased reduced glutathione (GSH) levels and increased
      malondialdehyde (MDA) formation. With the same concentrations a marked oxidative
      effect of 4,5-NO2 was observed. Significant correlations between 4,5-NO2
      concentrations, GSH levels and lipid peroxidation, and also between GSH and MDA
      levels, were observed. Increasing radiation doses decreased erythrocyte membrane
      sensitivity to the stabilizing effect of unsaturated fatty acids. This effect for
      oleic acid was elevated by 4,5-NO2 and suppressed by GSH and BHT. Therefore, it
      is concluded that in aerobic conditions the red blood cell membrane is a target
      to radiation and to hypoxic cell radiosensitizers.

PMID- 1974579
TI  - Early modifications of outgrowth and metallo-endopeptidase activity in
      fibroblasts from rat cutaneous explants after local gamma-irradiation: dermis
      cellularity and collagen fibre alterations.
AB  - The initial response to local gamma-irradiation of skin was investigated in
      fibroblasts from cutaneous explants after doses of 4, 8, 12, 16 or 20 Gy. On the
      day of irradiation, fibroblast outgrowth was inhibited in a dose-dependent
      manner, but by day 7 post-irradiation, cell restoration occurred especially in
      explants exposed to 4 or 8 Gy. The dose-dependent inhibition of fibroblast
      outgrowth correlated with the decrease in cellular metallo-endopeptidase (MEP)
      activity against succinyl trialanine paranitroanilide. However, the secretion of
      this MEP activity was 10-fold higher in the culture medium after the lowest
      irradiation dose (4 Gy). Its inhibition profile was not modified after local
      irradiation, whatever the dose. In vivo, the cell density of mastocytes,
      pericytes and endothelial cells decreased after irradiation. Moreover, damaged
      collagen was observed in the superficial dermis after local irradiation. These
      results strongly suggest that this MEP may be involved in the alterations
      occurring in dermal connective tissue components after skin irradiation. The
      rapid decrease with the dose in fibroblast outgrowth and MEP activity also
      suggests that these two parameters may provide useful tools for dosimetric assay
      of the heterogeneity and extent of irradiated areas.

PMID- 1974580
TI  - Quantitative study of wound infection in irradiated mice.
AB  - Bacterial infection of simple wounds was studied directly and quantitatively in
      adult mice given 6.5 Gy 60Co. Three days later, when neutropenia was evident, the
      skin and the medial gluteus muscle of anaesthetized mice were incised. A
      suspension of Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae or
      Streptococcus pyogenes was inoculated into the wound. Bacteria per mg muscle were
      enumerated 3, 4 or 7 days later. The geometric means of bacteria per mg were
      greater in irradiated than in non-irradiated mice. Phagocytic cells were present
      in the wounded tissue. Hence sublethal ionizing radiation enhanced the
      susceptibility of mice to infections of wounds by these four bacterial species.

PMID- 1974581
TI  - Dose and dose-splitting effects of X-rays on lung tumour induction in mice.
AB  - This paper reports lung-tumour induction 12 months after single or split doses of
      X-rays in C3H/He male mice. The early proliferative response of lung cells after
      doses which induced lung tumours was also examined after single X-irradiation.
      The lung-tumour incidence tended to increase with increasing dose after a single
      irradiation and peaked at 5 Gy. At more than 10 Gy it decreased sharply to the
      control level. The mean tumour diameters tended to increase with doses up to 7.5
      Gy and then decreased beyond 10 Gy. These results suggested that suppression of
      tumour growth reduced the tumour incidence at doses of over 10 Gy. The lung
      tumour incidence decreased with increasing intervals between two equal doses of
      2.5 or 5 Gy. The decrease was thought to be caused by the repair of the
      tumorigenic injury. However, the tumour incidence after two 2.5 Gy irradiations
      at 1 day intervals or two 5 Gy irradiations at 6 h intervals was higher than that
      observed after a single dose. This phenomenon was regarded as a progression of
      the tumorigenic injury. The labelling indices of the lung cells, determined using
      tritiated thymidine after a single irradiation, were higher than those of non
      irradiated control cells. This response was delayed as the dose increased. The
      responses versus days after irradiation could be classified into three patterns
      on the basis of their peaks. The possibility that the larger delay after higher
      doses had some relation to the reduction of target cells for tumour incidence is
      suggested.

PMID- 1974582
TI  - Flow cytometric determination of the time of metastasis during fractionated
      radiation therapy of the rat rhabdomyosarcoma R1H.
AB  - A technique is presented for determining the time of metastasis during
      fractionated radiation therapy of the rat rhabdomyosarcoma R1H by flow cytmetric
      DNA index measurements. The DNA index is the relative DNA content of the tumour
      cells compared with normal cells. The DNA index of the highly hyperploid R1H
      tumour decreases linearly during radiation therapy dependent on the total dose
      applied, with a rate of 0.22% per Gy. Since metastatic cells escape further
      irradiation, their DNA index should correspond to the DNA index at time of
      spread. If so, cells disseminated late during a course of fractionated
      irradiation are expected to produce symptoms later and to have a lower DNA index
      compared with cells that metastasized at the start of treatment. The results
      obtained fitted these expectations, showing that timing of metastases by DNA flow
      cytometry, in principle, is possible. A first application of this method
      indicates that the risk per clonogenic R1H tumour cell to matastasize increases
      during fractionated irradiation.

PMID- 1974583
TI  - Distribution of 241Am in offspring from BALB/c mice injected with 241Am at 14
      days of gestation: relation to calcium and iron metabolism and comparison with
      distribution of 241Am after injection of adults.
AB  - Pregnant mice were given intravenous injections of 241Am citrate at 14 days of
      gestation. The fetal skeleton had a higher or similar uptake of 241Am per gram of
      fresh tissue than the liver. In comparison, the liver in adults concentrated 5 to
      20 times more 241Am per gram of fresh tissue than the bones. Measurement of
      changes in calcium and iron content and concentration with time, showed that in
      the developing mice intensive calcification of bones determined the uptake of
      241Am. The 241Am uptake was related to the calcium concentration of the fetal
      bones, which was greater at 14 days of gestation in the anterior bones, the
      mandibles and calvaria, than in the ribs and femurs. Transfer of 241Am to pups
      via milk resulted in further accumulation of 241Am in the skeleton and liver. The
      incorporation in the skeleton persisted after weaning and contributed to the
      lifetime body burden. The 241Am concentration decreased rapidly with time after
      injection in relation to the growth of the organs. Radiation dose rates and
      cumulative radiation doses were calculated for liver and bones of contaminated
      offspring.

PMID- 1974584
TI  - Effects of radiation on immature medullary cells in mouse hair.

PMID- 1974585
TI  - Polyarteritis nodosa presenting as bilateral sudden onset cochleo-vestibular
      failure in a young woman.
AB  - Sudden onset sensorineural hearing loss is an otological emergency. Although
      deafness is recognised as being associated with polyarteritis nodosa (PAN) only
      very rarely does it herald the disease. We describe a case of bilateral, sudden
      onset vestibulo-cochlear failure which with thorough investigation proved to be
      the presenting complaint of PAN. This diagnosis enabled definitive management of
      a multi-system disorder and resulted in an improvement of the initial symptom
      with the chemotherapeutic regime discussed. We review the involvement of PAN in
      deafness and hope this case will remind otolaryngologists of the need for full
      investigation of the above mentioned emergency, in an attempt to discover and
      hence direct management towards a specific underlying pathology.

PMID- 1974586
TI  - Cholera, shock and hypersensitivity: their actions on a final common path-
      intestinal intrinsic nerves.

PMID- 1974587
TI  - Experimental implantation of human umbilical vein grafts in dogs.
AB  - Locally produced human umbilical vein grafts (HUVG), using glutaraldehyde as a
      stabilizing agent, were implanted into 24 mongrel dogs. Different arterial bypass
      procedures, using HUVG, were carried out in three experimental groups. In Group
      I, 2 dogs underwent femorofemoral crossover bypass procedures and 6 dogs received
      aortoiliac bypass procedures. Thrombus formation was found in all HUVG implants
      of Group I. In Group II, 8 dogs received abdominal aorta HUVG interposition. In
      Group III, 8 dogs received abdominal aorta HUVG bypass procedures. Patent HUVG
      implants without thrombus formation, demonstrated by postoperative angiogram,
      were found in 6 dogs of Group II and 5 dogs of Group III. Morphological and
      histological studies of the patent HUVG implants retrieved after sacrifice showed
      on sign of rejection, biodegeneration, or aneurysmal formation. Our preliminary
      experience with this cost-effective locally produced human umbilical vein graft
      material was promising and may pave the way to further clinical applications.

PMID- 1974588
TI  - Hemodynamic changes after hepatectomy in rats studied with radioactive
      microspheres.
AB  - It has been difficult to measure hepatic arterial blood flow and portal venous
      flow simultaneously, especially in small animals. Radioactive microspheres were
      used in this experiment to quantitate splanchnic hemodynamics after hepatectomy
      in rats. With a reference sample technique, a certain amount of radioactive
      microspheres was injected into the left ventricle. The reference sample was
      withdrawn from the femoral artery at a constant rate. The animal was killed with
      a bolus of saturated KCl. The kidneys and splanchnic organs were removed and
      weighed. The radioactivity of each organ was determined using a gamma
      scintillation counter. Organ blood flow was calculated by the following formula:
      [formula: see text] Immediately after partial hepatectomy, a decreased cardiac
      index from 32.31 +/- 10.12 to 23.44 +/- 3.21 ml/(min x 100g body weight) (p less
      than 0.05), decreased hepatic arterial blood flow from 0.40 +/- 0.12 to 0.33 +/-
      0.03 ml/(min x g liver) (p less than 0.05), increased portal venous inflow from
      0.90 +/- 0.30 to 2.20 +/- 0.26 ml/(min x g liver) (p less than 0.05) and
      increased total hepatic blood flow from 1.30 +/- 0.39 to 2.53 +/- 0.26 ml/(min x
      g liver) (p less than 0.005) were observed. With an intrasplenic injection of an
      additional amount of radioactive microspheres, the ratio of lung/(lung + liver)
      radioactivities indicated the degree of portal systemic shunt (PSS). Though the
      portal pressure was elevated after hepatectomy (8.80 +/- 0.7 vs 11.9 +/- 1.7 cm
      H2O, p greater than 0.05), the extent of PSS was negligible (0.02 +/- 0.01% vs
      0.03 +/- 0.01%, p greater than 0.05). The radioactive microspheres with the
      reference sample technique is a simple, rapid, reliable and reproducible method
      for investigating the hemodynamic changes following partial hepatectomy.

PMID- 1974589
TI  - Hemodynamic and clinical efficacies of catheter balloon percutaneous transvenous
      mitral commissurotomy: experience of 100 patients with rheumatic mitral stenosis.
AB  - From January 1987 to December 1988, 100 patients with symptomatic severe
      rheumatic mitral stenosis underwent percutaneous transvenous mitral
      commissurotomy (PTMC). The patients included 32 males and 68 females, aged 19-71
      years (mean of 41). Mild mitral regurgitation (grade 1 or 2) was present in 23
      patients and a history of thromboembolism in 12. One patient had had mitral
      restenosis after surgical open mitral commissurotomy 9 years earlier. The mitral
      valve was successfully dilated in 97 patients. PTMC resulted in immediate
      improvements in hemodynamic measurements. The left atrial pressure decreased from
      24.5 +/- 5.3 to 14.8 +/- 5.2 mmHg (p less than 0.001), the mean mitral
      transvalvular gradient from 13.8 +/- 4.8 to 5.0 +/- 2.8 mmHg (p less than 0.001),
      and the mean pulmonary artery pressure from 38.8 +/- 12.0 to 30.6 +/- 10.3 mmHg
      (p less than 0.001). The mitral valve area increased from 1.1 +/- 0.3 to 2.2 +/-
      0.8 cm2 (p less than 0.001). The cardiac output increased from 4.5 +/- 1.2 to
      4.84 +/- 1.2 L/min (p less than 0.05). The right atrial pressure did not change
      significantly after PTMC (6.5 +/- 3.8 vs 6.4 +/- 4.0 mmHg). The mitral valve area
      measured by 2-D echocardiograms increased from 1.04 +/- 0.48 to 1.88 +/- 0.66 cm2
      after PTMC (p less than 0.001). All 97 patients were followed for 6-24 months
      (median of 13) after the PTMC. After an initial recovery period of 1-2 weeks, all
      patients reported improvements in symptoms and in New York Heart Association
      (NYHA) functional class by at least one class. A comparison between treadmill
      exercise test durations before, and 3 months after PTMC, showed an increase from
      9.1 +/- 4.3 to 15.4 +/- 3.8 minutes (n = 60; p less than 0.001).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1974590
TI  - Cerebral blood flow velocity in newborn infants with asphyxia.
AB  - A pulsed-Doppler real-time technique was used to assess the anterior cerebral
      artery (ACA) flow velocity in 30 asphyxiated infants during the first 5 days
      after birth. Thirty healthy term infants were also studied as controls. Peak
      systolic flow velocity (PSFV), end diastolic flow velocity (EDFV), mean flow
      velocity (MFV), and pulsatility index (PI) were measured. Mean PI values of the
      ACA of the asphyxiated and control groups were 0.63 +/- 0.05 vs 0.71 +/- 0.04 (p
      less than 0.001) on the first day; 0.64 +/- 0.03 vs 0.70 +/- 0.05 (p less than
      0.001) on the third day and 0.69 +/- 0.04 vs 0.70 +/- 0.04 (p greater than 0.05)
      on the fifth day of life. The asphyxiated group also had significantly higher
      EDFV and MFV than those of control group until the 5th day of life. The low PI
      values of asphyxiated infants were mainly due to an increase in EDFV. These
      results suggest that the cerebrovascular resistance of asphyxiated infants, as
      reflected by the PI, is low during the first 3 days of life, indicating an
      increase in cerebral blood flow. With this technique, we can repeatedly and
      safely evaluate the cerebral hemodynamic changes in asphyxiated newborn infants.

PMID- 1974591
TI  - Prenatal diagnosis of hemophilia A by DNA analysis of chorionic villi.
AB  - Hemophilia A is an X-linked recessive single gene disease. If a female is a
      carrier, her sons have a 50% risk of being affected. Five gravidas, each with a
      positive family history of hemophilia A, were collected for prenatal diagnosis
      using DNA analysis on chorionic villi. We used two closely linked extragenic DNA
      markers, St14 and DX13, and three restriction enzymes, TaqI, MspI, and BglII, to
      study four restriction fragment length polymorphisms in the Xq28 region. From
      family analysis, haplotypes were constructed to track the inheritance of X
      chromosomes. In family 1, the male fetus inherited the X-chromosome from his
      normal grandfather, thus his probability of being affected was predicted to be
      less than 5%. In families 2 and 3, the gravidas inherited the maternal X
      chromosome with a different haplotype from that of the affected brother or
      nephew, thus they both have a low probability (less than 5%) of being carriers.
      In family 4, the gravida and her male fetus inherited the same X-chromosome as
      her affected brother. With coagulation assay also showing a high probability of
      the gravida being a carrier, the fetus was at high risk for the disease. On
      pregnancy termination, fetal plasma analysis confirmed the diagnosis. In family
      5, the gravida's mother had homozygous haplotypes, making the distinction between
      two X-chromosomes impossible. Coagulation assay classified the gravida as a
      probable carrier.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1974592
TI  - Rapid laboratory diagnosis of human cytomegalovirus infection using monoclonal
      antibody.
AB  - The monoclonal antibody E. 13, recognized an early nonstructure antigen (68 KD)
      of human cytomegalovirus (HCMV), was used for early detection of HCMV in cell
      cultures. The virus antigen could be detected by the indirect immunofluorescence
      staining (IF) technique 6 hours after inoculation of HCMV AD169 and NTUH871233
      strains into human embryonic lung fibroblast (HELF) cells growing in shell vials
      prepared by low speed centrifugation (700xg) at 25 degrees C for 1 hour. The
      intensity of fluorescence reached a peak 14 hours after virus inoculation and
      remained at the same level for 72 hours. The feasibility of application of this
      technique for rapid detection of HCMV in the clinical virology laboratory was
      tried. A total of 201 urine specimens requesting HCMV isolation were inoculated
      into HELF cells using the shell vial culture method. The virus growth in the
      shell vial cultures was detected by the indirect IF technique with the monoclonal
      antibody E.13 at 16 to 18 hours postinoculation. The results obtained were
      compared with those of the conventional tube culture method. The sensitivity and
      specificity of the test vs the conventional tube culture method for detection of
      HCMV in clinical specimens were 93.06% and 99.22%, respectively. The average time
      of virus isolation by the conventional culture method was 10.9 days, whereas
      final results with the shell vial culture method were obtained in only one day.
      The above results indicate that detection of HCMV early antigen in infected cells
      with monoclonal antibody E.13 is a sensitive and reliable method for rapid
      diagnosis of HCMV infections.

PMID- 1974593
TI  - Proliferation, interleukin-2 production and receptor expression in peripheral
      blood mononuclear cells from colorectal cancer patients.
AB  - Peripheral blood mononuclear cells (PBMC) were cultured with phytohemagglutinin
      (PHA) in 46 colorectal cancer patients and 27 normal controls. By collectively
      comparing the cancer patients with the normal controls, the cancer patients had:
      (1) decreased interleukin-2 (IL-2) secretion, (2) fewer interleukin-2 receptor
      (IL-2R) expression on cell surface, and (3) less 3H thymidine incorporation. The
      ability of the phorbol ester, phorbol 12-myristate 13-acetate (PMA), and the
      calcium ionophore, A23187, in co-stimulation with PHA, to enhance the IL-2
      secretion, IL-2R expression and 3H thymidine incorporation were studied in the
      PBMC of colorectal cancer patients. By adding A23187 into the PHA-stimulated PBMC
      from colorectal cancer patients, IL-2 production and IL-2R expression were
      increased up to levels equal to that obtained in PHA-stimulated PBMC from normal
      controls. Whereas there was no significant increase in proliferative response.
      However, PMA has no effect on all three parameters. A23187 is known to be
      effective in elevating cytosolic free Ca2+ and PMA is regarded as an activator of
      protein kinase C. Therefore, we may conclude that the impairment of IL-2
      production and IL-2R expression in PHA-stimulated cultures is mainly due to
      failure of the free Ca2+ release which can be repaired by A23187. While protein
      kinase C activation may not be impaired since its deficit in IL-2 production and
      IL-2R expression can not be corrected by PMA.

PMID- 1974594
TI  - Correlation of in vitro chemosensitivity and clinical responses to anticancer
      drugs in primary adenocarcinoma of the lung.
AB  - Cancer cells were isolated from either pleural effusion or tumor biopsies of 16
      patients with primary adenocarcinoma of the lung. Human tumor clonogenic assay
      was then performed using the double layer agar system. The cells were
      continuously exposed to 8 kinds of anticancer drugs, including adriamycin,
      vincristine, 5-FU, mitomycin C, cyclophosphamide, cisplatin, methotrexate and
      BCNU (carmustine) for 14 days in the following concentrations: 0.01, 0.1, 0.5, 1,
      5 and 10 micrograms/ml. A more than 50% reduction in colony counts was regarded
      as responsive. Active drugs were selected by observing colony reduction at a
      specific upper concentration for each individual agent. Combinations of the 1 to
      4 most potent drugs as recognized by in vitro chemosensitivity tests were given
      to the patients. Drainage of the fluids or pleurodesis was avoided. Assessment of
      patients' clinical conditions was made at the 8th week following chemotherapy.
      Thirteen (81.3%) patients showed a marked decrease in the amount of effusion,
      improvement in symptoms and signs and/or a decreased serum CEA level. It is
      concluded that chemosensitivity in vitro correlates well with clinical responses
      and recognition of effective drugs prior to treatment may improve the results of
      chemotherapy of primary lung adenocarcinomas.

PMID- 1974595
TI  - Renal excretion of zinc in patients with chronic uremia.
AB  - Though uremic patients have been reported to have subnormal zinc levels in plasma
      and an abnormal zinc metabolism, data on their renal excretion of zinc are still
      unavailable. In our study, 55 nondialyzed uremic patients had a markedly lower
      concentration of zinc in plasma and a lower urinary zinc excretion. They had a
      higher excretory fraction of zinc in the renal tubules and a higher ratio of zinc
      to creatinine excretion than normal subjects. We found that the total daily
      excretion of zinc, calcium, phosphate and ammonia was reduced, and that the ratio
      of calcium or ammonia to creatinine excretion decreased in uremic patients.
      Urinary zinc excretion was correlated with renal creatinine clearance (r = 0.50,
      p less than 0.001) in both normal subjects and uremic patients, but ammonia
      excretion was correlated with zinc excretion in normal subjects only. In uremia,
      urinary zinc excretion was correlated with urinary calcium (r = 0.55, p less than
      0.001) and urinary phosphate excretion (r = 0.30, p less than 0.05). We conclude
      that the increased ratio of zinc to creatinine excretion and the excretory
      fraction of zinc in the renal tubules of uremic patients may increase the urinary
      zinc excretion, but a severe diminution of the glomerular filtered load of zinc
      may be the major factor in decreasing the urinary zinc excretion in uremia.

PMID- 1974596
TI  - Prevalence of mottled enamel after 12 years of water fluoridation in Chung-hsing
      New Village.
AB  - The prevalence of mottled enamel (dental fluorosis) was investigated among
      children, aged 6 to 15 years, in Chung-hsing New Village and in Tsao-tun Village.
      The drinking water in Chung-hsing New Village has been fluoridated for 12 years
      at a level of 0.6 ppm, while the drinking water in Tsao-tun contains a negligible
      level of 0.08 ppm. The degree of mottled enamel was assessed by using Dean's
      Index and the Community Fluorosis Index (CFI), the latter being derived from
      Dean's Index for the purpose of comparison. In Dean's Index, 6 classes based on
      the severity of the mottling, are identified: normal, questionable, very mild,
      mild, moderate, and severe. The results showed that children in Chung-hsing had
      whiter teeth than those in Tsao-tun Village. In the fluoridated group, 5.8% of
      children fell into the "very mild" mottling category, as compared to 0.9% in Taso
      tun, the control area. For the "mild" class, the rate was 1.9% for Chung-hsing
      New Village and 0.4% for Tsao-tun. With only one exception in Tsao-tun, none of
      the children in the two groups showed mottling in the "moderate" or "severe"
      classes. The Community Fluorosis Index (CFI) was 0.15 for the Chung-hsing group,
      indicating that the occurrence of mottled enamel is very low when compared with
      data from fluoridation programs in other countries. It is concluded that in
      Taiwan, a 0.6 ppm fluoride concentration in drinking water, which has previously
      been reported to be effective in prevention of dental caries, is associated with
      only negligible mottling of enamel. Even when mottling does occur, the degree is
      very mild and only small chalky spots can be seen on the teeth.

PMID- 1974597
TI  - Aortico--left ventricular communication: report of a case.
AB  - An 11-month-old male infant whose condition had been followed since birth was
      referred to the National Taiwan University Hospital for management of a
      congenital heart disease. On admission, this infant was noted to have a systolic
      and diastolic precordial thrill and a grade 4/6 systolic and diastolic murmur.
      Echocardiography, cardiac catheterization and cineangiogram revealed aortic
      stenosis, aortic regurgitation and dilatation of the aortic root. Surgical repair
      was performed to correct this congenital anomaly due to the progressive
      congestive heart failure. Intraoperatively, a breach between the aortic valve and
      the edge of the sinus of Valsalva along the aortic annulus was found. This
      congenital defect was repaired with a Teflon patch successfully. Postoperatively,
      this patient convalesced steadily and was discharged. We report this unique case
      with aortico-left ventricular communication which we believe to be the ninth case
      in the English-language literature and the first in the Republic of China.

PMID- 1974598
TI  - Embedded hard contact lens: reports of a case.
AB  - Contact lens migration into the upper eye lid with resultant lid mass is a rare
      complication of hard contact lens wear. We present a case in which a cosmetically
      unacceptable upper lid mass was the chief problem. The patient had switched to
      soft contact lenses and tolerated them well for about 13 months. From computed
      tomographic scan pictures and the keratoscopic change, surgical exploration
      through the opening of a discharging sinus in the upper forniceal area delivered
      a 8 x 8 mm hard contact lens and a flux of tenacious mucoid discharge. Double
      eversion of the upper tarsus, which was advised by Green in 1963, was the most
      important technique in reaching the correct diagnosis, and it should be stressed
      again on examining patients with a history of displaced hard contact lens.

PMID- 1974599
TI  - [Prostatic cancer: an analysis of 42 cases].
AB  - Between January 1972 and December 1983, 42 cases of adenocarcinoma of the
      prostate were admitted to Kaohsiung Medical College Hospital. The ages ranged
      from 46 to 90 years, with a mean of 68.6 years. The peak age group was 60-79
      years of age and 2.3 per cent were less than 50 years old. The prospect for
      prognosis was worse if the serum acid phosphatase level was elevated. The over
      all 5-year survival rate of this series was 21%. The survival rate varied
      according to the clinical stage: Stage A, 40%; Stage B, 31.5%; Stage D, 6.25%. On
      the basis of our study, the most promising approach toward increasing the
      survival of patients with cancer of the prostate would be earlier detection and
      immediate definitive treatment, including radical prostatectomy and castration.
      The importance of an annual physical examination, especially in men over 50 years
      of age which includes digital palpitation of the prostate gl, is emphasized.

PMID- 1974600
TI  - [Primary small cell carcinoma of the kidney: report of a case].
AB  - Primary small cell carcinoma (SCC) of the kidney is an extremely rare neoplasm.
      The morphological, immunohistological and ultrastructural features are closely
      akin to primary SCC of the lung. The case of a 38-year-old married male,
      nonsmoker, with primary small cell carcinoma of the kidney and associated
      multiple bony metastases is reported. Roentgenographic studies exhibited a tumor
      mass 3 cm in diameter over the middle portion of the left kidney. A CT scan of
      the cervical and thoracic spines, and a whole body bone scan displayed multiple
      osteolytic lesions suggesting multiple bony metastatic lesions. A chest X ray and
      CT scan of the nasopharynx demonstrated no significant lesions. A complete workup
      was performed followed by a left nephrectomy. Histologically, the tumor revealed
      SCC of the kidney. Immunohistochemically, the tumor cells demonstrated
      immunoreactivity to cytokeratin (CK), neuron-specific enolase (NSE) and produced
      negative stains to argentaffin, argyrophil, S-100 and chromogranin A.
      Ultrastructurally, these neoplastic small cells revealed a few cytoplasmic dense
      core neuroendocrine-type differentiated secretory granules, measuring 110 to 115
      nm in size. Thus, adjuvant therapy, supplemented with chemotherapy and
      radiotherapy, was employed. The patient was alive and well 6 months after
      surgery. To the best of our knowledge, there are four documented cases of primary
      SCC of the kidney. In this article, the light microscopic, immunohistochemical
      and ultrastructural studies of renal SCC are presented and suggest a renal pelvic
      epithelial origin of renal SCC. Cognitively renal SCC appears to be an aggressive
      tumor, regardless of the degree of neuroendocrine differentiation.

PMID- 1974601
TI  - Phosphoinositide breakdown in rat hippocampal slices: sensitivity to glutamate
      induced by in vitro anoxia.
AB  - We examined the effects of in vitro anoxia on phosphoinositide (PI) breakdown in
      rat hippocampal slices stimulated by glutamate and quisqualate. In addition to
      assays of accumulations of 3H-inositol phosphates (3H-IPs) degraded from
      prelabeled PI, we adopted direct assay procedures of inositol 1,4,5-triphosphate
      (1,4,5-IP3) using 1,4,5-IP3-specific binding protein to determine the formation
      of 1,4,5-IP3. The first effect, observed with anoxic incubation by itself, was
      the diminished quisqualate (10(-5) M)-stimulated accumulation of 3H-IPs degraded
      from prelabeled PI under prolonged anoxia. Quisqualate caused a transient
      increase in 1,4,5-IP3 formation in the early phase of anoxia, similar to that
      under oxygenated conditions. Glutamate (10(-5) M), under normal conditions,
      influenced neither the accumulation of 3H-IPs nor the formation of 1,4,5-IP3.
      Also, the accumulation of 3H-IPs under prolonged anoxia was unaffected. The same
      concentration of glutamate, however, gave rise to a transient increase in 1,4,5
      IP3 content in the early phase of anoxia, similar to that caused by quisqualate.
      The second effect, observed by oxygenation following anoxia, was the induction of
      glutamate-stimulated accumulation of 3H-IPs. When the hippocampal slices were
      oxygenated following a sufficiently long (greater than 30-min) exposure to
      anoxia, glutamate (10(-5) M) caused a significant increase in accumulation of 3H
      IPs degraded from prelabeled PI. Quisqualate-stimulated accumulation of 3H-IPs
      under oxygenated incubations was also increased by prior exposure of slices to
      anoxia. These results support the hypothesis that an exposure of hippocampal
      slices to anoxia induces a sensitivity of the PI breakdown pathway to glutamate
      and that, given an oxygen supply following sufficiently long exposure to anoxia,
      the slices maintain their sensitivity to glutamate with an apparent increase in
      the accumulation of 3H-IPs.

PMID- 1974602
TI  - Preloading in vivo: a rapid and reliable method for measuring gamma-aminobutyric
      acid and glutamate fluxes by microdialysis.
AB  - In vivo microdialysis was used in conjunction with a novel dual-label preloading
      method, to monitor changes in extracellular levels of gamma-aminobutyric acid
      (GABA) and glutamate in the striatum of conscious, unrestrained rats. [3H]GABA
      and [14C]glutamate were applied in the dialysis stream for a preloading period of
      30 min, after which dialysis perfusion was continued for up to 6 h, and dialysate
      samples were collected for scintillation counting. Veratridine (Vtd: 100 microM
      in the dialysate) caused significant rises in both 3H and 14C content measured in
      the dialysates, the majority of which remained associated with the preload GABA
      and glutamate, respectively. The Vtd-stimulated release of GABA and glutamate
      measured in this way was blocked by tetrodotoxin and was Ca2+ dependent. Thus, by
      reproducing results obtained using other techniques, we have shown that the
      preloading method provides a quick and reliable method for measuring the effects
      of drugs on the release of neurotransmitter GABA and glutamate in vivo by
      dyalisis. It should enable sample times as low as 1 min to be used, thus allowing
      resolution of transient stimulated responses taking place over a time course of
      minutes.

PMID- 1974604
TI  - Induction of ornithine decarboxylase in cerebral cortex by excitotoxin lesion of
      nucleus basalis: association with postsynaptic responsiveness and N-methyl-D
      aspartate receptor activation.
AB  - The major cholinergic innervation of the rat cerebral cortex arises from the
      nucleus basalis in the basal forebrain. Introduction of the excitotoxins kainate
      or ibotenate into the nucleus basalis by stereotaxic injection results in
      degeneration of the cholinergic cells. We have investigated the effect of this
      excitotoxic action on ornithine decarboxylase (ODC) activity and cholinergic
      responsiveness in the cerebral cortex. A massive and rapid induction of ODC
      activity was seen in ipsilateral cortex after injection of excitotoxin. A maximal
      increase in ODC activity of 268 times the control value was seen in ipsilateral
      cerebral cortex 8 h after lesioning. Thereafter, ODC activity declined but
      remained significantly greater than control levels for 32 h. Pretreatment of
      animals with the irreversible ODC inhibitor difluoromethylornithine prevented the
      induction of ODC by kainate. Tissue content of the ODC product putrescine showed
      a marked increase in cerebral cortex ipsilateral to the lesion, increasing
      sevenfold at 24 h, the maximal concentration reached. After 24 h, the level of
      putrescine decreased but remained significantly elevated above control values for
      5 days. Levels of the polyamines spermidine and spermine were unaffected by
      lesioning. Increases on ODC activity of much smaller magnitude were also seen in
      brain regions not directly innervated from the ipsilateral nucleus basalis.
      However, the response in ipsilateral cortex was found to be dependent on an
      intact projection from nucleus basalis to cortex. The induction of ODC was shown
      to be prevented by treatment of rats with MK-801, a result indicating the
      involvement of N-methyl-D-aspartate (NMDA) receptors.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1974603
TI  - Pharmacological characterization of somatostatin receptors in the rat cerebellum
      during development.
AB  - Somatostatin (SRIF) receptors (SRIF-Rs) are transiently expressed in a
      germinative lamina of the rat cerebellum, the external granule cell layer. The
      appearance of SRIF-Rs coincides with the expression of SRIF-like immunoreactivity
      in the cerebellum. However, the cellular location of SRIF-Rs does not overlap
      with the distribution of SRIF-like immunoreactivity, with the latter being
      restricted to ascending fibers arising from the brainstem, to perikarya within
      the white matter, and to some Purkinje cells. The characterization of SRIF-Rs in
      the immature (13-day-old) rat cerebellum was conducted by means of binding
      experiments in membrane-enriched preparations and autoradiography, using two
      radioligands, [125I-Tyr0,D-Trp8]SRIF-14 [( 125I-Tyr0,D-Trp8]S14) and 125I-SMS 204
      090. The pharmacological profile of cerebellar SRIF-Rs was compared with that of
      adult cortical SRIF-Rs. Saturation studies performed in 13-day-old rat cerebellum
      showed that the KD values for [125I-Tyr0,D-Trp8]S14 and 125I-SMS 204-090 binding
      were 0.35 +/- 0.04 and 0.39 +/- 0.01 nM, respectively. The corresponding Bmax
      values were 52.7 +/- 4.8 and 49.9 +/- 5.3 fmol/mg of protein, a result indicating
      that radioligands with high specific radioactivity (2,000 Ci/mmol) bind to a
      single class of high-affinity sites (SS1). Competition studies showed that
      different D-Trp-substituted analogs displaced [125I-Tyr0,D-Trp8]S14 binding with
      Hill coefficients less than 1, a finding indicating the existence of different
      subtypes of binding sites. When [Tyr0,D-Trp8]S14 was used as a competitor, two
      sites were resolved by Scatchard analysis in both 13-day-old cerebellum and adult
      cerebral cortex.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1974605
TI  - Ontogeny of tyrosine hydroxylase concentration in locus coeruleus of newborn
      rats: long-term effects of RU24722.
AB  - The ontogenetic variations of tyrosine hydroxylase (TH) have been studied in
      locus coeruleus of developing rats. During the first 2 weeks after birth, a large
      increase in TH content (6.04-23.99 TH units) in the noradrenergic structure was
      observed, followed by a period of progressive increase of the protein
      concentration (42 TH units in adult rats). The expression of TH was studied in
      the same ontogenetic period after treatment by RU24722 (20 mg/kg, i.p.). The long
      term increase in TH concentration produced by the drug was found to follow
      ontogenetic variations. It becomes significant around the middle of the second
      week after birth and gradually increases until the 24th day of postnatal
      development, indicating a maturation of the mechanisms involved in the inducing
      effect.

PMID- 1974607
TI  - The effect of some preservatives used in nasal preparations on the mucus and
      ciliary components of mucociliary clearance.
AB  - Efficient mucociliary clearance is a function of the physical properties of the
      mucus coupled to appropriately functioning cilia and may be altered by substances
      affecting ciliary beat frequency (CBF). Therefore the effect of preservatives on
      CBF was investigated using a photoelectronic technique. Methyl-p-hydroxybenzoate,
      propyl-p-hydroxybenzoate, chlorbutol and chlorocresol inhibited beat frequency,
      an effect which was reversible upon rinsing out the first three compounds but not
      chlorocresol. The effect of chlorhexidine and phenylmercuric borate on CBF was
      complicated by an interaction with chloride ions in the media used. EDTA did not
      appear to be ciliotoxic, while the effect of benzalkonium chloride was variable.
      Thiomersal halted ciliary beating after 40-100 min. Mucociliary clearance may
      also be affected by an alteration of the physical properties of the mucus layer,
      therefore the effect of each compound on the rheological properties of purified
      pig gastric mucus glycoprotein was investigated. None of the preservatives
      significantly altered the viscoelastic properties of the gel, measured using
      dynamic techniques.

PMID- 1974606
TI  - Plant-derived neurotoxic amino acids (beta-N-oxalylamino-L-alanine and beta-N
      methylamino-L-alanine): effects on central monoamine neurons.
AB  - In the present study the subacute effects of beta-N-oxalylamino-L-alanine (BOAA)
      and beta-N-methylamino-L-alanine (BMAA) on CNS monoamine neurons in rats were
      investigated following intracisternal injections or local intracerebral
      administration into substantia nigra. In vitro effects of BOAA and BMAA on high
      affinity synaptosomal uptake of dopamine (DA), noradrenaline (NA), and serotonin
      (5-HT) were also examined. Intracisternal administration of BMAA decreased NA
      levels in hypothalamus, whereas no effects were seen on DA or 5-HT levels.
      Following intranigral injections of BOAA, NA levels tended to decrease in several
      regions, whereas the DA levels and the levels of DA metabolites were unaffected
      in all regions analyzed. Loss of tyrosine hydroxylase (TH) immunoreactivity in
      the intranigral injection sites and the presence of TH-immunoreactive pyknotic
      neurons near the borders of the injection sites were observed following both BOAA
      and BMAA treatments. Furthermore, substance P-immunoreactive terminals in
      substantia nigra pars reticulata were also found to have disappeared within the
      lesioned area following either BOAA or BMAA injections. Incubations with both
      BOAA and BMAA (10(-5) M) reduced high-affinity [3H]NA uptake in cortical
      synaptosomes to 69% and 41% of controls, respectively, whereas the striatal high
      affinity [3H]DA uptake and the cortical high-affinity [3H]5-HT uptake were
      unaffected by BOAA or BMAA. The results demonstrate that both BOAA and BMAA can
      affect central monoamine neurons, although the potency and specificity of these
      substances on monoamine neurons when administered acutely into cerebral tissue or
      liquor cerebri seem to be low. However, the in vitro studies indicate selective
      effects of both compounds on NA neurons in synaptosomal preparations.

PMID- 1974608
TI  - Permeability of cellulose polymers: water vapour transmission rates.
AB  - The water vapour transmission rates (WVTR) through solvent cast polymer films
      prepared from cellulose acetate, cellulose acetate propionate, and cellulose
      acetate butyrate have been determined. They were influenced by the relative
      humidity, the substituent type and the extent of substitution. Increasing the
      relative humidity from 32 to 90% increased the WVTR 3 to 5 times depending on the
      polymer used. The WVTR increased in the order of butyrate less than propionate
      less than acetate. An increase in the extent of substitution with acetyl and/or
      butyryl groups resulted in an exponential decline in the WVTR.

PMID- 1974609
TI  - Moisture sorption profiles and tensile strength of tableted phenobarbitone
      formulations.
AB  - The tensile strength of tablets made from phenobarbitone and sodium
      phenobarbitone formulations after storage at increasing ambient relative humidity
      has been investigated. The moisture sorption and desorption profiles of the
      formulations were analysed for three locations of moisture: monolayer adsorbed
      moisture, normally condensed moisture and absorbed moisture. Maxima in tensile
      strength occur at moisture distributions determined by the disintegrant used. The
      changes in tensile strength have been explained in terms of changes produced in
      the interparticle separation, the range of the interparticle forces and changes
      in the ratio of the binding to diffusional forces, acting on the water molecules
      which are on the particles' surface.

PMID- 1974610
TI  - Decrease in penbutolol central response as a cause of changes in its serum
      protein binding.
AB  - Penbutolol is a beta-adrenoceptor antagonist that is extensively bound to alpha 1
      acid glycoprotein (alpha 1-AGP), a protein that increases in inflammatory
      diseases thereby binding more drug in such conditions. Changes in serum binding
      can lead to modifications in the pharmacokinetics and pharmacodynamics of a drug,
      therefore, the central effect (as the anticonvulsant response) and brain uptake
      of penbutolol given intravenously to mice with experimental inflammation have
      been measured. A significant decrease of the central effect of penbutolol and its
      brain uptake was seen in diseased when compared with control animals (P less than
      0.01). A parallel decrease in free fraction of penbutolol in diseased vs normal
      animals was detected. These results suggest that there is an increase in serum
      binding of basic drugs related to increments in alpha 1-AGP concentration, which
      reduces their central pharmacological effect.

PMID- 1974612
TI  - Modulation of the GABAA receptor by barbiturates and pregnane steroids:
      differential effects of the influence of assay temperature.
AB  - The effect of temperature on the modulation of the GABAA receptor by barbiturates
      and steroids has been investigated in-vitro using a radioreceptor binding assay.
      Displaceable [3H]muscimol binding to a crude membrane preparation from rat
      cerebral cortex was enhanced by the endogenous steroid metabolite, 5 beta-pregnan
      3 alpha-ol-20-one, by the synthetic steroid, alphaxalone, and by pentobarbitone
      in a dose-dependent manner. Hydrocortisone and corticosterone had no significant
      effect on [3H]muscimol binding. Analysis of binding data using a curve-fitting
      program ('Ligand') showed that both pentobarbitone (1 mM) and 5 beta-pregnan-3
      alpha-ol-20-one (10 microM) increased the apparent number of high affinity
      binding sites in the membrane but had no effect on the affinity of [3H]muscimol
      binding (Kd approx. 11 nM). Increasing the assay temperature from 0 degrees C to
      35 degrees C decreased [3H]muscimol binding and decreased the enhancement of
      binding by pentobarbitone but had no effect on 5 beta-pregnan-3 alpha-ol-20-one
      enhancement of binding. 5 alpha-Pregnan-3 alpha-ol-20-one increased the apparent
      rate of association of [3H]muscimol binding to its receptor whereas
      pentobarbitone had no effect. These different effects on the apparent association
      rate and the different responses to temperature, suggest that the barbiturate and
      steroid may interact with the GABAA receptor through different binding sites.

PMID- 1974611
TI  - In-vivo radiolabelled oxiracetam binding to rat brain.
AB  - The in-vivo binding of [3H]oxiracetam has been studied in brain areas of rats
      examined 30 min after i.c.v. injection. Soluble radioactivity accounted for more
      than 90% of total radioactivity in all the structures considered and was not
      affected by co-injection with a 1000-fold excess of unlabelled oxiracetam. Both
      total and bound radioactivity showed a marked regional distribution, with highest
      concentrations in the septum, followed by the hippocampus; the cerebral cortex,
      striatum and cerebellum had the lower concentrations of radioactivity. Computer
      assisted quantitative autoradiography with [14C]oxiracetam confirms these
      findings. Analysis of [3H]oxiracetam bound to membranes indicated that, after co
      injection with a 1000-fold excess of unlabelled oxiracetam, there was a
      significant reduction of binding only in the septum, hippocampus and cerebral
      cortex. These results suggest that in those cerebral structures oxiracetam binds
      to saturable sites.

PMID- 1974613
TI  - Cyclosporin treatment alters prostanoid and thromboxane production by rat
      isolated kidney mitochondria.
AB  - This study was designed to investigate the effects of chronic treatment with
      cyclosporin A (CSA) on the endogenous synthesis of prostanoids (PGs) and
      thromboxane (Tx) by renal isolated medullary and cortical mitochondria. The
      administration of CSA, dissolved in 10% ethanol in olive oil, to male Wistar rats
      (20 mg kg-1 day-1 i.p.) for 14 days resulted in alterations in mitochondrial
      biosynthesis of immunoreactive PGs. The endogenous synthesis of thromboxane by
      medullary and cortical mitochondria isolated from CSA-treated rats was
      significantly enhanced by 120 and 55%, respectively, whereas the synthesis of
      prostaglandin E2 by medullary mitochondria was reduced by 35%. The synthesis of
      prostaglandin F2 alpha and prostacyclin was not affected by CSA treatment. The
      conversion of exogenous arachidonic acid to PGs and Tx by cortical mitochondria
      isolated from CSA-treated rats was significantly increased. In addition, CSA
      treatment resulted in i) a reduced acylation of arachidonic acid into medullary
      phospholipids by 25% and into medullary and cortical triglycerides by 33 and 27%,
      respectively, and ii) an increase in cortical and medullary triglycerides. We
      suggest that the alterations in the endogenous mitochondrial production of PGs
      and Tx caused by CSA, may play a role in the impairment of membrane mediated
      functions.

PMID- 1974614
TI  - Halothane, isoflurane and enflurane potentiate the effect of noradrenaline on
      ventricular automaticity in the rat heart: evidence of the involvement of both
      alpha- and beta-adrenoceptors.
AB  - Direct evidence has been sought as to what extent the sensitization of heart to
      the arrhythmogenic action of sympathomimetic drugs in the presence of the
      inhalatory anaesthetics, halothane, isoflurane and enflurane, is mediated by
      either alpha- or beta-adrenoceptors. For this purpose, the effects of
      isoprenaline, noradrenaline and phenylephrine on ventricular automaticity induced
      by local injury have been studied in the isolated right ventricle of the rat.
      Isoprenaline was more potent in increasing ventricular automaticity than either
      phenylephrine or noradrenaline. The anaesthetic potentiated the effects of
      noradrenaline, as well as that of higher concentrations of phenylephrine, but not
      those of isoprenaline. These results support the contention that increases in
      ventricular automaticity induced by sympathomimetic drugs are mainly mediated by
      adrenoceptors of the beta-type. However, the simultaneous activation of both
      alpha- and beta-adrenoceptors seems to be necessary for the effect of the
      anaesthetics in sensitizing the heart to sympathomimetic drugs.

PMID- 1974615
TI  - Characterization of cysteinyl-leukotriene formation in primary astroglial cell
      cultures.
AB  - The formation and composition of cysteinyl-leukotrienes (LT) in primary
      astroglial cell cultures prepared from newborn rat brain has been studied. Small
      amounts of cysteinyl-LT determined in terms of LTC4-like material in the
      supernatants of the cultures, became detectable after stimulation of the cells
      with 10(-5) M ionophore A23187. Cysteinyl-LT formation increased with time,
      reaching about 600 pg (mg protein)-1 after 60 min incubation. In contrast,
      considerable thromboxane (TX) B2 synthesis was found at 5 min following A23187
      stimulation (about 30 ng TXB2 (mg protein)-1). The synthesis of cysteinyl-LT was
      abolished by 5 x 10(-5) M nordihydroguaiaretic acid (NDGA). Irrespective of the
      duration of incubation, blockage of prostanoid synthesis by 10(-6) M indomethacin
      did not result in increased cysteinyl-LT production. Reversed phase HPLC combined
      with radioimmunological detection showed that, after 60 min incubation in the
      presence of A23187, LTC4 and LTD4 accounted for practically all the LTC4-like
      immunoreactive material in the supernatants of cell cultures. No significant
      amounts of LTE4 could be detected. The results show that astrocytes may
      contribute to brain LTC4 and LTD4 synthesis. However, the cellular site of
      cerebral LTE4 formation seems to be other than the astroglia.

PMID- 1974616
TI  - Increased proliferation of phytohaemagglutinin (PHA)-stimulated human leucocytes
      after 8-methoxypsoralen treatment.
AB  - The effect of 8-methoxypsoralen on human blood mononuclear cells cultured in
      darkness has been examined. 8-Methoxypsoralen (1 microgram mL-1, 4.6 microM)
      added to (phytohaemagglutinin-stimulated cells induced a two-fold increase in the
      number of mitoses. The number of blastic cells also increased. There was no
      effect on the formation of micronuclei and there was no chromosomal breakage.

PMID- 1974617
TI  - Enhancing effect of combining two pyrrolidone vehicles on transdermal drug
      delivery.
AB  - The enhancing effect of combining 1-methyl-2-pyrrolidone (MP) and 1-lauryl-2
      pyrrolidone (LP) as the vehicles for transdermal penetration of
      phenolsulphonphthalein (phenol red) has been investigated by using an in-vitro
      technique with excised rat skin. LP had a higher enhancing effect on the
      penetration of phenol red than MP, but there was a long lag time before steady
      state penetration was attained. A potent effect with a shorter lag time was
      obtained when MP and LP were used together. This potentiation was maintained when
      the concentration of MP was decreased by 95%. The combined vehicle also enhanced
      the skin accumulation of phenol red. MP promoted the rapid penetration of LP into
      the skin and potentiated the enhancing effect of LP on the penetration of phenol
      red and thereby shortened the lag time. The combined vehicle also enhanced the
      penetration of the hydrophilic anticancer agent, 5-fluorouracil.

PMID- 1974618
TI  - Glycyrrhetinic acid derivatives: anti-nociceptive activity of deoxoglycyrrhetol
      dihemiphthalate and the related compounds.
AB  - The possible inhibitory effect of deoxoglycyrrhetol dihemiphthalate (I) and the
      related compounds (18 beta-olean-9(11),12-diene-3 beta,30-diol) (II) and (olean
      11,13(18)-diene-3 beta, 30-diol) III derived from glycyrrhetinic acid has been
      examined on acetic acid-induced writhing in mice. The compounds inhibited
      writhing dose-dependently. Their ED50 values were 14, 31 and 22 mg kg-1 for I,
      II, and III, respectively. The compounds like aspirin, also significantly
      suppressed PGE2 production in peritoneal fluid together with the writhing
      response. The results suggests that the analgesic effect of deoxyglycyrrhetol
      dihemiphthalate and the related compounds is partially due to inhibition of PGE2
      production.

PMID- 1974619
TI  - Circadian phase dependent acute toxicity and pharmacokinetics of etidocaine in
      serum and brain of mice.
AB  - The aim of this study was to investigate the possible influence of the time of
      administration on etidocaine acute toxicity and kinetics in mice. Different
      groups of adult male NMRI mice maintained under controlled environmental
      conditions (lights on 06.00-18.00) were injected at one of the following times:
      10.00, 16.00, 19.00, 22.00, 01.00 and 04.00 h with four doses of etidocaine at
      each time point to establish the acute toxicity (LD 50). To assess
      chronokinetics, a single 40 mg kg-1 i.p. dose of etidocaine was given to adult
      male NMRI mice at four fixed times: 10.00, 16.00, 22.00 and 04.00 h. Etidocaine
      serum levels were determined by GLC. The data showed significant 24 h variations
      of the Cmax only (highest value = 9.64 +/- 1.31 micrograms mL-1 at 10.00 P less
      than 0.05; amplitude, (maximum-minimum) mean x 100 = 84%) Vd, (amplitude =
      59.7%), alpha and beta phase elimination half-lives (amplitude = 52 and 35%,
      respectively), clearance (amplitude = 23%) and AUC infinity 0 (amplitude = 22%)
      were not found to be significantly time dependent. Etidocaine kinetics in brain
      were determined similarly; a significant temporal variation was found for the
      elimination half life (amplitude, 161.9%) and AUC (amplitude, 133.2%) but not for
      Cmax. These data demonstrate a temporal pattern of etidocaine kinetics similar to
      those reported previously for other local anaesthetic agents, bupivacaine and
      mepivacaine. The temporal changes in etidocaine induced acute toxicity may result
      in part from its chronokinetic changes.

PMID- 1974620
TI  - Pharmacological modulation of 2-methyl-carbamate-PAF induced rat paw oedema.
AB  - Intraplantar injections of 2-methyl-carbamate-PAF (2-MC) (0.125-16.0
      micrograms/paw) into the rat paw were followed by a bell-shaped dose response
      curve for inflammatory oedema, with an ascending phase at 0.125-2.0
      micrograms/paw, and a descending phase at 4.0-16.0 micrograms/paw. The
      inflammatory response to 2-MC was partially inhibited by pre-treatment with
      aspirin (200 mg kg-1), NDGA (100 mg kg-1), dexamethasone (0.1 mg kg-1), verapamil
      (50 mg kg-1) and by a specific PAF antagonist BN 52021 (5-10 mg kg-1). The cyclo
      oxygenase inhibitors indomethacin (2 mg kg-1) and piroxicam (1.8 mg kg-1) as well
      as antihistamine meclizine (40 mg kg-1) and ranitidine (50 mg kg-1) failed to
      block the oedematogenic response to 2-MC. Our data suggest that 2-MC induced rat
      paw oedema is mediated by PAF-acether receptors and is partially dependent on
      arachidonate lipoxygenase pathway and extracellular Ca2+.

PMID- 1974621
TI  - Hyperoxia and salicylate metabolism in rats.
AB  - Following the administration of aspirin to rats by gavage, both 2,3- and 2,5
      dihydroxybenzoate appeared in the plasma. The concentration of the 2,3
      dihydroxybenzoate was significantly higher in animals exposed to 100% O2 for 60 h
      than in air breathing controls. These data are evidence that increased salicylate
      hydroxylation is associated with oxidative stress.

PMID- 1974622
TI  - Correlation of phenol sulphotransferase activities in the liver and platelets of
      rat.
AB  - Phenol sulphotransferase (PST) activity in rat platelet cytosol for p-nitrophenol
      (PNP) sulphation was found to have a similar dependence on PNP concentration and
      thermostability to that in rat liver cytosol. The activities of PST isoenzyme for
      the sulphation in the microM range of PNP in rat platelets and rat liver were
      significantly correlated. Thus, measurement of PST activity in platelets could be
      a useful and practical method for predicting this activity in liver.

PMID- 1974623
TI  - The vascular relaxant effects of guanabenz are not mediated by alpha 2
      adrenoceptors in rat aortic rings.
AB  - The present experiments show that the alpha 2-adrenoceptor agonist guanabenz
      produced a concentration-dependent relaxation in 5-hydroxytryptamine- and
      noradrenaline-preconstricted rat aortic rings, but not when tone was raised by
      high potassium in the medium. Similar findings were made for pinacidil. In 5
      hydroxytryptamine-preconstricted preparations the relaxant effect of guanabenz
      was not affected by yohimbine, propranolol or by removal of the endothelium. In
      noradrenaline-preconstricted rings the relaxant effects of guanabenz and
      pinacidil were significantly antagonized by tetraethylammonium. The results
      suggest that guanabenz might act in the muscle tissue by opening potassium
      channels or antagonism of calcium mobilization from intracellular stores.

PMID- 1974624
TI  - Choline is an inhibitory modulator of cholinergic nerve function in guinea-pig
      colon.
AB  - Using the novel smooth muscle-myenteric plexus (smmp) preparation from the guinea
      pig colon, it has been possible to measure acetylcholine (ACh) overflow by a
      radiolabelling technique. The possibility that choline may be a modulator of
      cholinergic nerve activity in this preparation was investigated by observing its
      effects on electrically-evoked overflow of [3H]acetylcholine. Choline (72, 144
      microM), in concentrations that did not contract the smmp preparation, caused a
      depression of electrically-evoked [3H]ACh overflow. This effect was unlikely to
      be due to actions on cholinesterase enzymes by end product inhibition. Choline
      also produced substantial non-muscarinic elevation of spontaneous [3H]overflow.
      It is concluded that inhibitory modulation of enteric cholinergic nerve activity
      by presynaptic muscarinic receptors may not be exclusively mediated by the
      actions of acetylcholine.

PMID- 1974625
TI  - Ability of ketanserin to block different receptors in human placental vessels.
AB  - 5-Hydroxytryptamine (5-HT), noradrenaline (NA) and histamine induced
      concentration-dependent contractions in segments of human chorionic arteries and
      veins, whereas clonidine, an alpha 2-adrenoceptor agonist, had no effect. 5-HT
      and histamine induced strong contractions, while NA elicited weak contractions in
      some segments. The maximal response was similar for 5-HT and histamine. The order
      of potency (EC50 values) was: 5-HT greater than or equal to NA greater than or
      equal to histamine. These agonists induced tachyphylaxis, and single
      concentrations caused transient contractions. Contractions elicited by 5-HT were
      antagonized by ketanserin, a 5-HT2-receptor antagonist, which also antagonized
      the responses to NA and histamine, but at greater concentrations than those
      needed for 5-HT responses. Contractions elicited by histamine were reduced by
      diphenydramine. Low concentrations of 5-HT amplified contractions caused by NA
      and histamine. The results indicate that: (i) 5-HT is the most potent constrictor
      agent tested in these vessels; (ii) its effects are mediated by 5-HT2-receptors;
      and (iii) ketanserin at therapeutic plasma concentrations (10(-7) M) seems to
      block mainly 5-HT2-receptors, and alpha 1-adrenergic- and H1-receptors to a small
      extent only.

PMID- 1974626
TI  - Beta-adrenoceptor antagonists and human sperm motility.
AB  - Several beta-adrenoceptor blocking agents have been evaluated for spermicidal
      activity using a transmembrane migration method. The rank order of potency of the
      active compounds was: penbutolol greater than (+)-propranolol greater than
      bufuralol greater than (-)-alprenolol greater than oxprenolol greater than
      metoprolol. Atenolol, pindolol, practolol, tolamolol were without activity. The
      observed potencies of spermicidal activity are believed to be unrelated to beta
      blocking activities, and we have shown that whilst they are not predictable from
      lipid solubility or nonspecific membrane properties of the compound alone, both
      these aspects appear to play a role in this pharmacological activity.

PMID- 1974627
TI  - Presence of non-cholinergic motor transmission in human isolated bladder.
AB  - Atropine-sensitivity of the motor transmission in the isolated detrusor
      preparation from human bladder has been examined. The preparations were
      contracted by electrical field stimulation consisting either of short trains of
      pulses or of long trains of pulses. Part of the stable response to short-train
      stimuli (28%) was resistant to atropine, was not potentiated by physostigmine and
      was blocked by tetrodotoxin. The stable responses to long-train stimuli were
      fully blocked by atropine. It is concluded that the detrusor of the bladder in
      man, in common with other mammalian species, contains a noncholinergic component
      in its motor transmission, and that prolonged stimulation with long-train stimuli
      causes an extinction of the non-cholinergic motor transmission, probably through
      depletion of transmitter stores in the nerve-terminals.

PMID- 1974628
TI  - A multicenter clinical trial of oral ribavirin in HIV-infected patients with
      lymphadenopathy. The Ribavirin-LAS Collaborative Group.
AB  - A double-blind, randomized, placebo-controlled trial comparing two daily doses of
      oral ribavirin and placebo was conducted at four medical centers. One hundred
      sixty-four adult men with lymphadenopathy were enrolled over a 2-month period and
      randomized to receive ribavirin 800 mg (53 subjects), ribavirin 600 mg (55
      subjects), or placebo (56 subjects). Active treatment was administered for 24
      weeks followed by a 4-week washout period. Nine subjects receiving placebo, four
      receiving ribavirin 600 mg, and none in the 800 mg group developed AIDS during
      the 24 weeks of active treatment. One patient randomized to the 800 mg group had
      Kaposi's sarcoma at study entry and was included in the intent-to-treat analysis.
      An overall significant difference in progression to AIDS was observed among the
      three treatment groups (p = 0.028) with patients randomized to receive 800 mg
      having a significantly longer time to AIDS than placebo patients (p = 0.012;
      relative risk, 9.0; 95% confidence interval, 1.1 to 70.8). There was no
      significant difference between the 600 mg and placebo groups (p = 0.15; relative
      risk, 2.3; 95% confidence interval, 0.7 to 7.6). Baseline CD4 cell count and
      hematocrit made independent contributions and formed a multivariate prognostic
      set for these progression data. The significant treatment superiority of 800 mg
      compared to placebo remained after adjustment for these factors (p = 0.019).
      After deletion of patients with major protocol violations at entry, the
      difference between the 800 mg and placebo treatment remained significant (p =
      0.021).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1974629
TI  - Modeling the decline of CD4+ T-lymphocyte counts in HIV-infected individuals.

PMID- 1974630
TI  - [Biological glues and biomaterials in periodontal surgery. Description of a
      surgical reattachment technic].
AB  - A major research problem over the past 10 years is to obtain a new attachment
      after treatment of roots previously exposed to periodontal disease. Among the
      most recent studies, two main objectives of surgery are suggested: a selection of
      cell population and to arrest epithelial migration by guided tissue regeneration
      with a membrane, and a biological and chemical root preparation with citric acid
      and fibronectin. A technique for the treatment of deep osseous lesion is put
      forward here: the association of biodegradable membrane--natural coral--citric
      acid and fibronectin.

PMID- 1974631
TI  - U-66444B and U-68553B, potent autoreceptor agonists at dopaminergic cell bodies
      and terminals.
AB  - U-66444B was evaluated for pre- and postsynaptic effects in dopaminergic (DA)
      cell body and nerve terminal regions of chloral hydrate anesthetized rats. U
      66444B depressed DA neurons in substantia nigra pars compacta and ventral
      tegmental area with a potency three times that for apomorphine. With a sufficient
      dose, cells were completely silenced. Activity was found to reside principally in
      the (+)-stereoisomer, U-68553B. The effects of U-66444B and U-68553B were
      reversed by 0.1 mg/kg haloperidol. Apomorphine, but not U-66444B nor U-68553B,
      depressions were accompanied by rapid tachyphylaxis. After 2 wk of U-66444B 0.6
      mg/kg/day, potency was not significantly affected. By using in vivo voltammetry,
      100 micrograms/kg U-68553B produced a depression in DA release that was more
      dramatic and more prolonged than that for 500 micrograms/kg apomorphine. On DA
      postsynaptic receptors, iontophoretic U-66444B and apomorphine were approximately
      equipotent in depressing caudate neuron firing. It is concluded that U-66444B and
      its active enantiomer, U-68553B, are more potent, longer acting and possibly more
      selective as DA autoreceptor agonists than apomorphine. The propensity to produce
      tolerance appears weak.

PMID- 1974632
TI  - Prevention and complete reversal of cyclosporine A-induced renal vasoconstriction
      and nephrotoxicity in the rat by fenoldopam.
AB  - The primary mechanism of cyclosporine A-induced nephrotoxicity involves renal
      vasoconstriction. In the present study, we have tested the effects of fenoldopam,
      a dopamine DA1, receptor agonist with renal vasodilator properties, on the
      changes in renal function induced by acute and subacute administration of
      cyclosporine A. In inactin-anesthetized rats, acute administration of
      cyclosporine A (100 mg/kg i.p.) significantly decreased paraaminohippuric acid
      (PAH) and inulin clearances. Fenoldopam, at a dose (10 micrograms/kg.min) which
      alone significantly increased PAH and inulin clearances, completely prevented the
      cyclosporine A-induced reductions in renal function. Similarly, subacute
      administration of cyclosporine A (20 mg/kg.day for 3 days) resulted in
      significant reductions in base-line PAH and inulin clearances which were
      normalized by administration of fenoldopam. These data indicate that
      administration of fenoldopam can both prevent and completely reverse cyclosporine
      A-induced renal vasoconstriction and nephrotoxicity.

PMID- 1974633
TI  - Interaction of intrathecal morphine and ST-91 on antinociception in the rat: dose
      response analysis, antagonism and clearance.
AB  - Physiological data suggest that the direct effect of spinal opiates as well as
      the activation of adrenergic bulbospinal pathways each results in a reduction in
      the gain of the stimulus response function in dorsal horn neurons. In its
      simplest form, this suggests the hypothesis that co-activation of spinal alpha2
      and opioid receptors should be manifested as a synergistic interaction in which
      in its simplest form the net effect would be a product of the effect produced by
      either drug alone. To assess this hypothesis, rats were prepared with chronically
      implanted intrathecal (IT) catheters. Dose-response curves for IT morphine were
      obtained in the presence of fixed doses (0.01 nmol, 0.03 nmol, 0.1 nmol, 0.3
      nmol) of 2-[2,6-dimethylphenylamino]-2-imidazoline (ST-91), an alpha 2 agonist.
      Such concurrent administration of ST-91 resulted in highly significant leftward
      shifts in the effect of morphine on the hot plate (52.5 degrees C) measure with a
      significant increase in dose-response curve slopes. To minimize the effects of
      the cut-off time necessary in an antinociceptive measure, a "Cox proportional
      hazard" analysis was used. The (log) Hazard function log[h(t)] is expressed as a
      linear function of the effects resulting from the action of morphine, the action
      of ST-91 and as a function of an interaction of morphine and ST-91, e.g., the
      general form is: log[h(t)] = alpha o(t) + beta 1.log doseM + beta 2.log doseST +
      beta 12.log doseM.log doseST Estimates of the principal coefficients beta 1, beta
      2 and beta 12 corresponding to the overall effect of morphine alone, ST-91 alone
      and the interaction between the two were calculated: beta 1, beta 2 and beta 12.
      A statistical test of the interaction coefficient revealed that beta 12 was
      significantly (p less than .001) different from zero, indicating the powerful
      synergy between IT ST-91 and morphine. Confirmation of the synergistic nature of
      spinal opioid alpha 2 receptors was provided by the fact that IT injection of
      naloxone (90 nmol) or phentolamine (100 nmol) after IT injection of various
      combinations of morphine and ST-91 immediately and completely abolished the
      potentiating effect of the combination. The clearance of IT [3H]morphine from the
      thoracic and lumbar spinal cord was not changed in the presence of ST-91. These
      observations suggest a potent synergistic interaction between spinal mu and alpha
      2 adrenergic receptor systems.

PMID- 1974634
TI  - Effects of buspirone and related compounds on suppressed operant responding in
      rats.
AB  - The novel anxiolytic drug buspirone and its analogues, gepirone and ipsapirone,
      have behavioral effects that differ substantially from those of other anxiolytics
      such as benzodiazepines and barbiturates. In particular, buspirone does not
      consistently produce large increases in rates of responding suppressed by
      punishment in rodents or primates. To study the effects of buspirone and other
      compounds on suppressed operant responding in rats, two procedures were used. In
      the first, food-reinforced responding was suppressed during a stimulus associated
      with response-produced electric shocks (punishment). Chlordiazepoxide produced
      large increases in rates of punished responding, but neither buspirone nor
      ipsapirone gave rise to a similar effect. In a second experiment, food-reinforced
      responding was suppressed during a stimulus that terminated with an unavoidable
      shock (conditioned emotional response). Chlorodiazepoxide and clorazepate
      increased suppressed response rates at low doses and decreased nonsuppressed
      responding at higher doses, giving rise to dose-related increases in suppression
      ratios. The effects of buspirone, gepirone and ipsapirone were similar to those
      of the benzodiazepines with ipsapirone producing particularly marked increases in
      responding during the pre-shock stimulus. 8-Hydroxy-2-(di-n-propylamino)tetralin
      did not consistently give rise to the same effect. In addition, similar effects
      were not produced by haloperidol, imipramine, morphine or idazoxan. Haloperidol
      and morphine decreased nonsuppressed responding without changing rates of
      suppressed responding or suppression ratios. Imipramine decreased rates of both
      nonsuppressed and suppressed responding and idazoxan decreased suppression
      ratios. The conditioned emotional response procedure may be more sensitive for
      assessing the behavioral effects of buspirone and similar anxiolytic drugs in
      rats than are punishment procedures.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1974635
TI  - Serotonin release contributes to the locomotor stimulant effects of 3,4
      methylenedioxymethamphetamine in rats.
AB  - Methylenedioxymethamphetamine (MDMA) is a phenylethylamine with novel mood
      altering properties in humans. MDMA shares the dopamine-releasing properties of
      amphetamine but has been found to be a more potent releaser of serotonin (5-HT).
      The present study undertook to determine the relative roles of dopamine and 5-HT
      release in MDMA-induced locomotor hyperactivity. S-(+)MDMA produced dose
      dependent increases of rat locomotion. Investigatory behaviors such as holepokes
      and rearings were suppressed by (+)MDMA. Pretreatment with the selective 5-HT
      uptake inhibitors fluoxetine, sertraline and zimelidine inhibited (+)MDMA-induced
      locomotor hyperactivity but failed to antagonize the reduction of holepokes and
      rearings. Because 5-HT uptake inhibitors have been found previously to block the
      MDMA-induced release of 5-HT in vitro, and because fluoxetine was found to have
      no effect on (+)amphetamine-induced hyperactivity, the present results suggest
      that (+) MDMA-induced locomotor hyperactivity is dependent on release of
      endogenous 5-HT. Additionally, prior depletion of central 5-HT with p
      chlorophenylalanine partially antagonized the (+)MDMA-induced hyperactivity,
      although catecholamine synthesis inhibition with alpha-methyl-p-tyrosine did not
      block the effects of (+)MDMA. Taken together, these studies suggest that (+)MDMA
      increases locomotor activity via mechanisms that are dependent on the release of
      central 5-HT and that are qualitatively different from the mechanism of action of
      (+)amphetamine.

PMID- 1974636
TI  - Characterization of alkaline response induced by cholinergic agents in the rat
      duodenum: involvement of M2 receptors and the calcium-dependent process.
AB  - Duodenal pH, potential difference and acid-neutralizing capacity (HCO3- output)
      were measured in anesthetized rats, in an attempt to characterize these responses
      induced by cholinergic agents. When the proximal duodenum (1.7 cm) was perfused
      at a flow rate of 1 ml/min with saline adjusted to pH 4.5, the pH, potential
      difference and HCO3- output were 5.2 to 5.5, -3 to -5 mV (mucosa negative) and
      1.5 to 1.8 muEq/10 min, respectively. Both carbachol (4 micrograms/kg, i.v.) and
      bethanechol (100 micrograms/kg, i.v.) significantly elevated all these parameters
      at the doses that stimulated gastric acid secretion; the net HCO3- output caused
      by these agents was about 35% of that produced by prostaglandin E2 (300
      micrograms/kg, i.v.). These responses induced by carbachol were significantly
      inhibited by pretreatment with verapamil (0.2 mg/kg, i.v.), a Ca channel blocker,
      and atropine (0.1 mg/kg, i.v.), a nonselective M1 and M2 antagonist, while they
      remained unaltered in the presence of pirenzepine (1 mg/kg, i.v.), a selective M1
      antagonist, or indomethacin (5 mg/kg, s.c.). However, the effects of
      prostaglandin E2 on duodenal pH, potential difference and HCO3- output were not
      significantly affected by any of these agents. These results suggest that the
      cholinergic agents stimulate HCO3- output in the duodenum, probably mediated by
      M2 receptors and through the Ca-dependent and electrogenic processes. Endogenous
      prostaglandins may not be involved in this mechanism.

PMID- 1974637
TI  - Napamezole, an alpha-2 adrenergic receptor antagonist and monoamine uptake
      inhibitor in vitro.
AB  - Napamezole (2-[3,4-dihydro-2-naphthalenyl)methyl]-4,5-dihydro-1H- imidazole
      monohydrochloride) is a selective alpha-2 adrenergic receptor antagonist and a
      monoamine re-uptake inhibitor in vitro. The alpha adrenergic antagonist activity
      of napamezole was determined in vitro in rat brain receptor binding assay using
      [3H]clonidine and [3H]prazosin for alpha-2 and alpha-1 receptors, respectively.
      The Ki values for napamezole were 28 nM (alpha-2) and 93 nM (alpha-1). The
      relative potencies for inhibiting [3H]clonidine binding were: phentolamine
      greater than idazoxan greater than napamezole greater than mianserin greater than
      yohimbine greater than piperoxan greater than rauwolscine greater than tolazoline
      much greater than prazosin; and for inhibition [3H]prazosin binding they were:
      prazosin greater than phentolamine greater than mianserin greater than napamezole
      greater than yohimbine greater than idazoxan greater than tolazoline. Alpha
      adrenoceptor antagonism was also assessed in the isolated rat vas deferens.
      Napamezole reversed clonidine-induced decreased in twitch height in the
      electrically stimulated rat vas deferens (alpha-2 antagonism with a Kb of 17 nM).
      The rank order of potency as an alpha-2 antagonist relative to other compounds
      was phentolamine greater than idazoxan greater than yohimbine greater than
      piperoxan = napamezole greater than mianserin much greater than prazosin.
      Napamezole also antagonized methoxamine-induced contractions (alpha-1) of the rat
      vas deferens with a Kb of 135 nM. The rank order of potency of these compounds as
      alpha-1 antagonists was prazosin greater than phentolamine greater than mianserin
      greater than yohimbine greater than napamezole greater than idazoxan.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1974638
TI  - In vivo assessment of napamezole, an alpha-2 adrenoceptor antagonist and
      monoamine re-uptake inhibitor.
AB  - Napamezole is an alpha-2 adrenergic receptor antagonist and a selective inhibitor
      of 5-hydroxytryptamine re-uptake in vitro. In the present study, napamezole was
      evaluated in vivo for its ability to antagonize alpha-2 adrenergic receptors and
      to inhibit 5-hydroxytryptamine re-uptake. The alpha-2 blocking activity of
      napamezole was demonstrated by its ability to: 1) antagonize clonidine-induced
      antinociception in mice (ED50 value, 36 mg/kg p.o.; 3 mg/kg s.c.); 2) enhance
      norepinephrine turnover in rat brain (minimum effective dose, 30 mg/kg p.o.); and
      3) enhance locus coeruleus neuronal firing (active at doses greater than or equal
      to 1 mg kg i.v.) and to reverse clonidine-induced suppression of locus coeruleus
      firing in rats. The rank order of potencies of napamezole and reference alpha-2
      antagonists to inhibit clonidine-induced antinociception (based upon s.c. ED50
      values) were: idazoxan greater than yohimbine greater than rauwolscine greater
      than or equal to napamezole greater than tolazoline greater than or equal to
      piperoxan greater than RS21361. The relative potencies of compounds to enhance
      alpha-methyltyrosine-induced depletion of forebrain norepinephrine following p.o.
      administration were: idazoxan = yohimbine greater than mianserin greater than
      napamezole greater than RS21361. The ability of each of these compounds to
      enhance alpha-methyltyrosine-induced depletion of rat-forebrain norepinephrine
      was reversed by the administration of clonidine. These results indicate that
      napamezole blocks alpha-2 adrenergic receptors in vivo.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1974639
TI  - Influence of the DA2-receptor agonist quinpirole on the guinea pig ileum.
AB  - The influence of the dopamine-receptor agonist quinpirole was studied in segments
      of the guinea pig ileum, mounted to measure longitudinal muscle activity. In
      concentrations selective for dopamine receptors (10(-9)-10(-7) M), quinpirole did
      not influence cholinergic twitch responses induced by transmural stimulation at
      supramaximal voltage, but it concentration-dependently facilitated them in the
      concentration range 10(-6) to 10(-4) M; the potency of quinpirole was similar to
      that of metoclopramide (ED50 values, 6.0 x 10(-6) M and 2.2 x 10(-6) M,
      respectively). Pretreatment of the tissues with 5-hydroxytryptamine or with the 5
      hydroxytryptamine receptor antagonists methysergide, ketanserin and R53434 did
      not influence the facilitatory effect of quinpirole. It was also not influenced
      by drugs blocking adrenoceptors, dopamine receptors, opioid receptors, muscarinic
      M1 receptors, GABAA receptors and inhibiting the synthesis of prostaglandins. It
      was antagonized by the nicotinic receptor antagonist hexamethonium but not by
      pentolinium. Quinpirole did not enhance contractile responses to acetylcholine
      and carbachol, but in high concentrations induced contractions in unstimulated
      preparations. It is concluded that quinpirole facilitates twitch responses in the
      guinea pig ileum via a prejunctional site of action. This effect is not related
      to activation of dopamine receptors, but the exact mechanism remains unclear.

PMID- 1974640
TI  - Norepinephrine and BRL 37344 stimulate adenylate cyclase by different receptors
      in rat brown adipose tissue.
AB  - The beta adrenergic activation of adenylate cyclase was examined in membrane
      homogenates of rat interscapular brown adipose tissue (IBAT). In control
      membranes, isoproterenol and norepinephrine (NE) stimulated adenylate cyclase
      with activation constants of about 20 and 300 nM, respectively. Exposure of rats
      to 4 degrees C for 3 days increased the maximal stimulation of adenylate cyclase
      to these agonists but did not alter the respective activation constants. The beta
      1-selective antagonist 1-(2-cyanophenoxy)-3-beta-(3-phenylureido)ethylamino-2-pr
      opa nol blocked isoproterenol stimulation of adenylate cyclase in control and
      cold-exposed membranes at a concentration 100 times lower than did the beta 2
      selective antagonist erythro-dl-1-(7-methylindan-4-yloxy)-3-isopropylaminobuta n
      2-ol. These data indicate that typical adrenergic agonists stimulate IBAT
      adenylate cyclase via beta 1 receptors. (R*,R*)-4-[2-[2 [9 3-chlorophenyl)-2
      hydroxyethyl]amino)propyl) phenyl]phenoxyacetic acid (BRL 37344), an atypical
      agonist with activity at the beta 3 receptor, stimulated adenylate cyclase in
      control membranes with an activation constant of approximately 700 nM. Membranes
      of cold-exposed rats exhibited a high affinity response to BRL 37344 similar to
      that seen in control membranes and, in addition, a low affinity response. BRL
      37344 stimulation of adenylate cyclase was unaffected by 1-(2-cyanophenoxy)-3
      beta-(3-phenylureido)ethyl-amino-2-prop anol, whereas stimulation by NE or
      epinephrine was potently blocked.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1974641
TI  - Metabolism of methylenedioxymethamphetamine: formation of
      dihydroxymethamphetamine and a quinone identified as its glutathione adduct.
AB  - The in vitro conversion of (+)-3,4-methylenedioxymethamphetamine and (-)-3,4
      methylenedioxymethamphetamine to the corresponding catecholamine, 3,4
      dihydroxymethamphetamine (N-methyl-alpha-methyldopamine), by rat liver microsomes
      was examined. Metabolite formation was monitored after short-term incubations
      using high-performance liquid chromatography-electrochemical detection to
      determine concentrations of the catecholamine. The formation of N-methyl-alpha
      methyldopamine exhibited enantioselectivity and levels were significantly higher
      after incubation of the (+)-isomer. The reaction appears to be cytochrome P-450
      dependent as it was sensitive to SKF 525A and carbon monoxide. The catecholamine
      was unstable and was metabolized rapidly to a compound capable of forming an
      adduct with glutathione (GSH) and other thiol compounds. This second oxidation
      did not appear to be cytochrome P-450-dependent but required NADPH and microsomal
      protein. Catecholamine oxidation was inhibited by superoxide dismutase and by
      reducing agents. The same catecholamine oxidation product, characterized as the
      GSH adduct, could be generated by a xanthine-xanthine oxidase mixture and by
      tyrosinase. Mass spectral data showed that it was a 1:1 amine GSH adduct. These
      results indicate that MDMA is oxidized by cytochrome P-450 to the catechol and
      the catecholamine oxidized by superoxide to a quinone to which GSH or other thiol
      functions add. The formation of this quinone and its thiol adducts may account
      for some of the irreversible actions of this compound on serotonergic neurons.

PMID- 1974642
TI  - Electrophysiological effects of selective D1 and D2 dopamine receptor agonists in
      the medial prefrontal cortex of young and aged Fischer 344 rats.
AB  - The effects of the selective dopamine D1 and D2 receptor agonists, SKF 38393 and
      N-0437, respectively, on the firing rate of medial prefrontal cortex (PFC)
      neurons were studied in young (3-5 months old), and aged (18 and 26 months old)
      Fischer 344 rats. Multibarrel glass micropipettes, filled with 1 mM SKF 38393 and
      N-0437, were lowered into the anteromedial cortical target area (PFC) of the
      mesocortical dopamine system in urethane-anesthetized animals. The drug solutions
      were locally applied by pressure ejection. In young rats, both agonists produced
      dose-dependent and reversible reductions in firing rates. However, the D2 agonist
      was approximately 10 times more potent than the D1 agonist in suppressing firing
      rate. Even at the highest doses, SKF 38393 rarely produced complete cessation of
      firing in PFC cells. Moreover, no evidence of synergism was observed when the two
      drugs were simultaneously applied. PFC neurons in aged rats were significantly
      subsensitive to locally applied SKF 38393, whereas no change in sensitivity to N
      0437 was observed. These results suggest that both D1 and D2 receptors are
      present in the PFC and that agonist occupancy of each of these receptors elicits
      an inhibition of PFC neuron discharge; furthermore, these data suggest an age
      related change in D1 dopamine receptor-mediated processes with no concomitant
      change in processes linked to the activation of D2 dopamine processes.

PMID- 1974644
TI  - Prostaglandin synthesis elicited by adrenergic stimuli in rabbit aorta is
      mediated via alpha-1 and alpha-2 adrenergic receptors.
AB  - The purpose of this study was to characterize the type of adrenergic receptor(s)
      involved in both prostaglandin (PG) synthesis and the contractile response
      elicited by adrenergic receptor agonists in the rabbit aorta. The synthesis of
      prostacyclin as measured by the production of 6-keto-PGF1 alpha was assessed in
      vitro after exposing the aortic rings to different adrenergic agonists.
      Norepinephrine (NE), selective alpha 1 adrenergic receptor agonists methoxamine
      (MET), phenylephrine (PHE) and cirazoline (CIR) and the alpha 2 adrenergic
      receptor agonists UK 14304 (UK) and xylazine (XYL), but not the beta adrenergic
      receptor agonist isoproterenol (ISP), enhanced 6-keto-PGF1 alpha synthesis in a
      concentration-dependent manner with following order of potency: NE greater than
      UK 14304 greater than XYL greater than PHE greater than MET greater than CIR. The
      NE-induced increased in 6-keto-PGF1 alpha synthesis was attenuated by the alpha 1
      adrenergic receptor antagonists prazosin (PZ) and corynanthine (COR) and by the
      alpha 2 adrenergic receptor antagonists rauwolscine (RW) and yohimbine (YOH). MET
      induced 6-keto-PGF1 alpha synthesis was reduced by PZ and COR but not by RW. UK
      induced 6-keto-PGF1 alpha synthesis was reduced by RW, YOH, and PZ, which also
      acts as alpha-2B receptor antagonist, but not by COR. In rabbit aortic rings,
      adrenergic agonists produced contraction with the following order of potency: NE
      greater than PHE greater than MET greater than CIR greater than UK greater than
      XYL.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1974643
TI  - Effects of benzoyltropine and tropacocaine on several cholinergic processes in
      the rat brain.
AB  - Benzoyltropine and tropacocaine are two contaminants of street-cocaine reported
      to have parasympatholytic activity. Because the mechanism underlying this
      activity is obscure, we investigated the effects of these compounds on several
      cholinergic processes: sodium-dependent choline uptake, sodium-independent
      choline uptake, acetylcholine synthesis, acetylcholine release (spontaneous and
      veratridine-induced) and binding of [3H]quinuclidinyl benzylate to muscarinic
      receptors. These studies used rat cerebral cortical synaptosomes, except for the
      receptor-binding studies, which used whole brain plasma membranes. Benzoyltropine
      and tropacocaine each inhibited sodium-dependent choline uptake and acetylcholine
      synthesis in a dose-related manner that was competitive with extracellular
      choline. Benzoyltropine was 4 to 5 times more potent in both actions than
      tropacocaine. Sodium-independent choline uptake was not affected by either
      compound. Benzoyltropine (30 microM) had no effect on the sodium-dependent uptake
      of norepinephrine, gamma-amino-butyric acid, glutamate or serotonin; tropacocaine
      (30 microM) inhibited only norepinephrine uptake at this concentration.
      Benzoyltropine and tropacocaine each inhibited the spontaneous and veratridine
      induced release of newly synthesized acetylcholine, but not via activation of
      presynaptic muscarinic receptors. Instead, each compound was able to attenuate
      the oxotremorine-induced inhibition of the release of acetylcholine, suggesting
      antimuscarinic activity. Binding experiments showed that benzoyltropine and
      tropacocaine were, respectively, about 1,000- and 10,000-fold less potent than
      scopolamine as receptor antagonists. Finally, we demonstrated that benzoyltropine
      accumulates in the rat brain after its peripheral injection (10 mg/kg i.p.) and
      remains there with a half-life similar to that of cocaine.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1974645
TI  - Ca2(+)-evoked [3H]dopamine release from synaptosomes is dependent on neuronal
      type Ca2+ channels and is not mediated by acetylcholine, glutamate or aspartate
      release.
AB  - Elevation of potassium concentrations ([K+]) in the presence of Ca2+ is the most
      common method of evoking neurotransmitter release from synaptosomes. However, we
      have been investigating a method of releasing dopamine from synaptosomes that
      does not involve using elevated [K+]. In this paradigm of neurotransmitter
      release, dopamine is released from synaptosomes, previously exposed to micromolar
      or lower [Ca2+], by 1.25 mM Ca2+ in the presence of non-depolarizing [K+] (4.5
      mM). The present experiments characterize the Ca2+ channel(s) involved in the
      Ca2(+)-evoked release of dopamine from synaptosomes, and determine whether the
      release is mediated by acetylcholine, glutamate or aspartate. omega-Conotoxin (10
      nM), which blocks N-, L- and possibly T-type voltage-sensitive Ca2+ channels
      (VSCC), inhibited the Ca2(+)-evoked [3H]dopamine release from either striatal or
      olfactory tubercle synaptosomes to less than 50% of control. Neither 1 microM
      nifedipine nor 1 microM verapamil, which block L-type VSCC, affected Ca2(+)
      evoked release. The N- and T-type VSCC blocker neomycin and the nonspecific Ca2+
      antagonist, cobalt2+, inhibited release to a greater extent than omega-conotoxin.
      At 1 mM, both compounds inhibited release to approximately 30% of control.
      Neither the excitatory neurotransmitter glutamate nor aspartate (2mM) affected 1
      microM LY-171555 (a dopamine D2 agonist) inhibition of Ca2(+)-evoked [3H]dopamine
      release. Also, the glutamate antagonist, glutamic acid diethyl ester, did not
      affect either Ca2(+)-evoked release or 1 microM LY-171555 inhibition thereof. The
      nicotinic antagonist hexamethonium (10 microM) and the muscarinic antagonist
      atropine (1 microM) were also ineffective in inhibiting Ca2(+)-evoked release or
      LY-171555 inhibition of release.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1974646
TI  - Tonic opioid inhibition of the pressor region of the rostral ventrolateral
      medulla of rabbits is mediated by delta receptors.
AB  - From previous observations, we have suggested that an endogenous opioid input
      tonically inhibits the pressor neurons of the rostral ventrolateral medulla
      (RVLM) of rabbits. In the present studies, the specific opioid receptor
      subtype(s) which may be activated by such an endogenous innervation were examined
      using local administration of selective antagonists. The RVLM pressor region of
      chloralose-anesthetized and artificially ventilated rabbits was functionally
      identified by local administration of L-glutamate (5 nmol). Selective blockade of
      neither mu nor kappa receptors in the RVLM after bilateral injections of beta
      funaltrexamine (300-900 pmol) or nor-binaltorphimine (1 nmol), respectively, had
      any effect on either mean arterial pressure or heart rate. Delta receptors were
      blocked with ICI 174,864 (30-300 pmol). After the highest dose, there was a
      significant pressor effect (+32 +/- 6 mm Hg, mean +/- S.E.), which was of
      immediate onset and rapid time course (approximately 15 min), and which was
      accompanied by a bradycardia. In contrast, vehicle injections or injection of an
      inactive analog (ICI 178,173) had no effects. These results, together with
      previous pharmacological and anatomical evidence, suggest that there exists an
      enkephalinergic input to the RVLM that tonically inhibits the presympathetic
      pressor neurons via activation of delta-opioid receptors.

PMID- 1974647
TI  - D1 receptors function to inhibit the activation of tuberoinfundibular dopamine
      neurons.
AB  - The effects of the D1 dopamine agonists SKF 38393 and CY 208-243 on the activity
      of tyrosine hydroxylase within tuberoinfundibular dopamine neurons were studied
      by measuring the accumulation of dihydroxyphenylalanine (DOPA) in the median
      eminence in vivo after inhibition of DOPA decarboxylase. SKF 38393 (5-20 mg/kg)
      and CY 208-243 (5-20 mg/kg) alone did not alter the accumulation of DOPA in the
      median eminence of male rats. However, the haloperidol-, reserpine- and
      neurotensin-induced increases in DOPA formation in the median eminence were
      antagonized dose-dependently by SKF 38393 (5-20 mg/kg i.p.) and/or CY 208-243 (5
      20 mg/kg i.p.). Treatment of rats with SCH 23390 (0.5 mg/kg i.p.), a selective D1
      antagonist, or loxapine (5 mg/kg i.p.), a dopamine antagonist with high affinity
      for D1 receptors, prevented the inhibitory effect of CY 208-243 on the
      haloperidol-induced activation of tyrosine hydroxylase in the median eminence.
      SKF 38393 did not inhibit the basal activity or the haloperidol-induced increase
      in activity of tyrosine hydroxylase in the striatum or nucleus accumbens. It is
      concluded that D1 receptor activation results in little or no effect on the basal
      rate of dopamine synthesis within tuberoinfundibular dopamine neurons, but under
      conditions in which the activity of tyrosine hydroxylase is increased D1 receptor
      stimulation results in a marked inhibition of the rate of dopamine synthesis
      within these neurons.

PMID- 1974648
TI  - Alpha-adrenoceptor mediated facilitation of acetylcholine release in the rat
      perfused heart.
AB  - Rat hearts were isolated with the vagus nerves intact and perfused, and the
      neuronal acetylcholine stores were pulse labeled with [14C]choline. The overflow
      of [14C]choline/acetylcholine evoked by extrinsic vagus nerve stimulation (3 Hz
      and 720 pulses or 10 Hz and 1200 pulses) was determined by liquid scintillation
      spectrometry and used as a measure for acetylcholine release. The postjunctional
      changes in atrial contraction and beating frequency were also recorded. Compared
      to controls, oxymetazoline and xylometazoline [but not clonidine, (3,4
      dihydroxyphenyl-amino)-2-imidazoline), methoxamine and norepinephrine] enhanced
      the evoked overflow of 14C-activity in a concentration-dependent manner without
      changing the ratio between choline and acetylcholine determined by paper
      chromatography. Norepinephrine (10 mumol/l) inhibited the evoked overflow in the
      presence of propranolol plus yohimbine. The oxyme-tazoline-induced increase in
      evoked overflow was unaffected by rauwolscine (1 mumol/l), idazoxan (0.3 and 5
      mumol/l), and yohimbine (0.3 and 5 mumol/l), but significantly reduced by
      phentolamine (5 mumol/l), prazosin (0.03 mumol/l), the (-)-enantiomer of WB 4101
      (0.1 mumol/l) and SK&F 104078 (3 mumol/l). The overflow of 14C-activity evoked by
      field stimulation was increased by oxymetazoline the absence and presence of
      hemicholinium-3. The results are compatible with an alpha-1 adrenoceptor-mediated
      facilitation of exocytotic acetylcholine release from the rat heart in vitro. The
      increase in evoked neurotransmitter overflow, however, was not accompanied by an
      increase in postjunctional heart responses to vagus stimulation due to
      nonselective blocking properties of the facilitating agonists.

PMID- 1974649
TI  - Characterization of the prejunctional beta adrenoceptors in canine bronchial
      smooth muscle.
AB  - Prejunctional beta adrenoceptors in canine bronchi (3rd to 6th order) were
      characterized by observing the effects of beta receptor agonists and antagonists
      on field stimulation-induced contractions and excitatory junction potentials
      (EJPs). Contractions were antagonized by norepinephrine (IC50 = 9.4 X 10(-7) M),
      isoproterenol (IC50 = 1.9 X 10(-8) M) or salbutamol (IC50 = 4.0 X 10(-8) M). EJPs
      were also decreased by all three agonists, with little or no effect on resting
      membrane potential or on carbachol-induced depolarization when used at
      concentrations sufficient to eliminate EJPs. These inhibitory effects were
      blocked by propranolol or timolol, as well as by the selective antagonists ICI
      89,406 (beta-1-selective) and ICI 118,551 (beta-2-selective); pA2 values for the
      selective antagonists were 8.4 and 7.2 (norepinephrine as agonist) or 6.5 and 9.0
      (salbutamol as agonist), respectively. Control responses were also sometimes
      potentiated by the nonselective antagonists. Schild plot analysis of the data
      indicated clearly that both beta-1 and beta-2 receptors are involved in the
      inhibitory effect. Electron microscopic studies showed this tissue to be densely
      innervated by adrenergic and cholinergic nerves with close apposition of
      adrenergic and cholinergic nerve varicosities, providing a structural basis for
      prejunctional interactions between them. From the data presented, we conclude
      that catecholamines act on prejunctional beta-1 and beta-2 receptors leading to
      inhibition of cholinergic neurotransmission in canine bronchi.

PMID- 1974650
TI  - The clinical effectiveness of atipamezole as a medetomidine antagonist in the
      dog.
AB  - The efficacy of atipamezole, a recently introduced alpha 2-adrenoceptor
      antagonist, in reversing medetomidine-induced effects in dogs was investigated in
      a clinical study. Dogs from eight Finnish small-animal hospitals were sedated
      with a 40-microgram/kg dose of the alpha 2-agonist medetomidine i.m. In the first
      part of the study (n = 319), a randomized, double-blind design with respect to
      the dose of atipamezole (0, 80, 160 and 240 micrograms/kg i.m.) was used. In a
      separate study (n = 358), which was an open trial, the selected dose of
      atipamezole was 200 micrograms/kg i.m. Atipamezole at dose rates of 80-240
      micrograms/kg rapidly and effectively reversed medetomidine-induced deep sedation
      analgesia, recumbency and bradycardia. The median arousal time after atipamezole
      was 3-5 min, and walking time was 6-10 min compared to greater than 30 min for
      both effects after placebo. Heart rate also increased in a dose-related manner
      after atipamezole administration. The investigators' overall evaluation of the
      ability of atipamezole to reverse the effects of medetomidine was 'good' in 90%,
      and 'moderate' in 9% of cases. Relapse into sedation was reported in three
      individual cases. Side-effects were minimal. It is concluded that at doses four-
      to sixfold the medetomidine dose, atipamezole is a highly effective and safe
      agent in reversing medetomidine-induced sedation-analgesia, recumbency and
      bradycardia in dogs in veterinary practice.

PMID- 1974652
TI  - Recovery from chronic rotavirus infection in mice with severe combined
      immunodeficiency: virus clearance mediated by adoptive transfer of immune CD8+ T
      lymphocytes.
AB  - Severe combined immunodeficient (SCID) mice lack both functional T and B cells.
      These mice develop chronic rotavirus infection following an oral inoculation with
      the epizootic diarrhea of infant mice (EDIM) rotavirus. Reconstitution of
      rotavirus-infected SCID mice with T lymphocytes from immunocompetent mice allows
      an evaluation of a role of T-cell-mediated immunity in clearing chronic rotavirus
      infection. Complete rotavirus clearance was demonstrated in C.B-17/scid mice 7 to
      9 days after the transfer of immune CD8+ splenic T lymphocytes from
      histocompatible BALB/c mice previously immunized intraperitoneally with the EDIM
      w strain of murine rotavirus. The virus clearance mediated by T-cell transfer was
      restricted to H-2d-bearing T cells and occurred in the absence of rotavirus
      specific antibody as determined by enzyme-linked immunosorbent assay,
      neutralization, immunohistochemistry, and radioimmunoprecipitation. Temporary
      clearance of rotavirus was observed after the transfer of immune CD8+ T cells
      isolated from the intestinal mucosa (intraepithelial lymphocytes [IELs]) or the
      spleens of BALB/c mice previously infected with EDIM by the oral route. Chronic
      virus shedding was transiently eliminated 7 to 11 days after spleen cell transfer
      and 11 to 12 days after IEL transfer. However, recurrence of rotavirus infection
      was detected 1 to 8 days later in all but one SCID recipient receiving cells from
      orally immunized donors. The viral clearance was mediated by IELs that were both
      Thy1+ and CD8+. These data demonstrated that the clearance of chronic rotavirus
      infection in SCID mice can be mediated by immune CD8+ T lymphocytes and that this
      clearance can occur in the absence of virus-specific antibodies.

PMID- 1974651
TI  - CREB regulation of cellular cyclic AMP-responsive and adenovirus early promoters.
AB  - The cyclic AMP (cAMP) response element-binding protein (CREB) has been
      demonstrated to be a key mediator of cellular promoter response to cAMP. The
      binding site for this protein in many cellular cAMP inducible promoters (CRE)
      contains the palindrome sequence TGACGTCA, which contains two half-sites for CREB
      binding. A related promoter element, with the core sequence TGACG, has
      significant homology to an AP1-binding site and contains only one half-site for
      CREB binding. A group of factors known as activating transcription factors (ATF)
      have been found to bind to the latter and related sequences found upstream of
      early adenovirus promoters induced by E1A, and these factors are highly
      homologous to the CREB protein. We wished to characterize CREB, c-jun, and c-fos
      binding to these sites in the somatostatin gene (CRE) and in the adenovirus early
      region 3 promoter (E3/ATF). Oligonucleotides complementary to each of these sites
      were used in gel retardation assays with in vitro-translated CREB protein. These
      studies indicated that CREB bound primarily as a dimer to both a single and two
      half-sites, though there was increased affinity to the double compared with the
      single half-site. The c-jun and c-fos proteins also bound to both the
      somatostatin CRE- and E3/ATF-binding sites, but CREB did not bind to AP1
      recognition sites nor was it capable of forming heterodimers with either c-jun or
      c-fos. Truncations of the CREB protein, which eliminated regions of the protein
      containing consensus sites for phosphorylation by protein kinase A, protein
      kinase C, and casein kinase II, bound to both the CRE and ATF sites, indicating
      that these consensus sites were not essential for DNA binding or dimer formation.
      Transfection of CREB and protein kinase A expression constructs into F9 cells
      with promoters containing either a single or two half-sites for CREB binding
      indicated that CREB was capable of similar levels of activation of these
      constructs. However, the fold activation by CREB was higher for constructs
      containing a single half-site compared with those containing two half-sites.
      These results demonstrate that multiple mechanisms may regulate CREB binding,
      including variations in the sequences in the promoter-binding site and the
      presence of related DNA-binding proteins.

PMID- 1974653
TI  - AGM1+ spleen cells contain gamma interferon (IFN-gamma) gene transcripts in the
      early, sex-dependent production of IFN-gamma after picornavirus infection.
AB  - Encephalomyocarditis D variant (EMCV-D)-infected spleen cell cultures prepared
      from diabetes-resistant ICR Swiss female mice produce more gamma interferon (IFN
      gamma) activity over a 24-h period than do spleen cell cultures from diabetes
      susceptible male mice of this strain. Pretreatment of mice with anti-asialo GM1
      eliminates early in vitro IFN-gamma production from 4 to 16 h postinfection
      (p.i.) and reduces IFN-gamma production from 16 to 24 h p.i. In this study,
      depletion of spleen cells with anti-Thy-1 by panning greatly reduced IFN-gamma
      activity in EMCV-D-infected spleen cell cultures throughout a 24-h period.
      Populations of asialo GM1 (AGM1), L3T4, and Lyt-2-positive cells were isolated
      from cells harvested at 9 h p.i. from EMCV-D-infected spleen cell cultures by a
      modified panning technique on polystyrene microscope slides. By in situ
      hybridization with a [35S]dATP-labeled IFN-gamma cDNA probe, only the AGM1
      bearing cells were found to contain detectable IFN-gamma gene transcripts. An
      AGM1+, Thy-1+ natural killer-like cell is the probable producer of the early, sex
      dependent IFN-gamma activity in this system.

PMID- 1974654
TI  - [The effect of corticosteroids on the recovery from vecuronium induced block].
AB  - The effects of corticosteroids (hydrocortisone, methylprednisolone) on the
      recovery time from the vecuronium induced neuromuscular block were studied using
      evoked potential measurements by stimulating ulnar nerve. Plasma concentrations
      of vecuronium were examined after the administration of hydrocortisone and
      methylprednisolone using high performance liquid chromatography in 78 surgical
      patients. Recovery time from the block induced by vecuronium was prolonged by
      corticosteroids. In case of hydrocortisone, this prolongation effect was
      significant (P less than 0.01). In the study of plasma concentration, blood
      samples were taken 40 minutes after administration of vecuronium, plasma
      concentration of vecuronium is significantly higher in patients given
      hydrocortisone (124 +/- 8.32 ng.ml-1) (mean +/- SE) than control patients (68.2
      +/- 4.71 ng.ml-1) (P less than 0.001). It is speculated that corticosteroids
      lower the clearance of vecuronium. Prolongation of recovery time from vecuronium
      induced block after the administration of corticosteroids may be explained not
      only by the direct effect of hydrocortisone on the neuromuscular junction but
      also by the effect of hydrocortisone to prolong the elimination of vecuronium
      from plasma.

PMID- 1974655
TI  - [Peptic ulcer and arachidonate cascade related compounds].

PMID- 1974656
TI  - [Clinicopathologic study on minute endocrine tumors of the pancreas--analysis of
      autopsy cases].
AB  - Using 800 autopsy cases (422 men, 378 women, mean age 78.7) mainly consisting of
      the aged, we made a clinicopathological analysis of endocrine tumors of the
      pancreas. The results were: 1) Endocrine tumors and similar lesions were found in
      24 cases (25 lesions). 20 lesions (20 cases) were determined as tumors and five
      lesions (five cases) as hyperplasia of Langerhans islet. 2) Prevalence of tumor
      was 10% (6/60) in the all-section group and 1.6% (12/738) in the three-section
      group. Grossly observed tumor was in a single case. 3) As for the size of tumors,
      35% of them were 1,000 microns or smaller. All of the five cases of hyperplastic
      lesions were 1,000 microns, or smaller in size. 4) None of the cases with tumors
      and hyperplastic lesions showed symptoms of excessive hormone. 5) In
      immunohistochemical analysis, hormone production was observed in all of the 20
      cases of tumor and multiple hormone production was found in 14 of them (70%). 5)
      Ductular or tubular structures were found in or adjacent to tumor in 12 cases
      (60%) and hyperplasia in one case (20%). 6) One lesion each of tumor and
      hyperplasia were found in a single case. Langerhans islets, 500 microns or larger
      in size, were found in three lesions of tumor (15%). Furthermore, langerhans
      islets with the diameter of mean + 2 SD or larger were found around five lesions
      of tumor (25%) and three lesions of hyperplasia (60%). Above findings suggest
      that endocrine tumors of the pancreas is highly prevalent and most of them do not
      go beyond asymptomatic tumors (non-functional in the broad sense of meaning) with
      no symptoms of excessive hormone though they produce some hormones. And it is
      indicated that some of the endocrine tumors or hyperplasias develop from
      totipotent stem cells of duct epithelia, and factors that promote the growth of
      Langerhans islets might exist.

PMID- 1974657
TI  - [A clinical study of drug-induced sinus node dysfunction].
AB  - beta blockers and Ca antagonists are popular therapeutic agents for hypertension
      and ischemic heart disease. Although these are reported to induce various
      bradycardiac arrhythmias, clinical studies remain insufficient. The author
      performed a clinical study of sinus node dysfunction caused by drugs for heart
      and circulatory diseases. Seventy-seven of the 1,734 patients admitted to the CCU
      of our hospital during the past 11 years, were the subjects of this study. They
      showed sinus node dysfunction on electrocardiographs (ECG). Forty-two subjects
      had drug-induced sinus node dysfunction (DISD) and 35 had sick sinus syndrome
      (SSS). Rubenstein's classification based on 12-lead ECG was used to diagnose DISD
      and SSS. All patients underwent chest X-ray examination, ECG, echocardiogram and
      blood chemistry and were divided into DISD and SSS groups. The DISD group was
      subdivided into an older group (65 years or more), and a younger group. Ten
      patients in the DISD group were examined electrophysiologically. SSS II and III
      types appeared in 22 DISD patients (52.3%) and in 31 SSS patients (88.5%).
      Bradycardia in the DISD group was milder than in the SSS group, because the DISD
      group had a higher minimum heart-rate and a shorter maximum R-R interval.
      However, the DISD group showed significantly lower blood pressure and renal
      function and a higher grade on the New York Heart Association's (NYHA)
      classification. Echocardiographic findings following recovery were similar in the
      two groups. Electrophysiological examination revealed abnormal sinus node
      function in 3 of the 10 DISD patients (30.0%). In the DISD group, 27 were older
      patients (3.2%). This was significantly more than the 15 who were younger
      patients (1.6%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1974658
TI  - [Mental health in software engineers. I. Frequency of mental complaints, physical
      complaints and psychiatric disorders].
AB  - This study examined the physical complaints, mental complaints and psychiatric
      disorders in software engineers. Subjects were 101 male software engineers. They
      were evaluated by a semistructured interview. Psychiatric diagnosis was based on
      DSM-III (Diagnostic and Statistical Manual of Mental Disorders, third edition).
      The results are summarized as follows: 1) Physical complaints were observed in
      68% of the subjects with 25% of the subjects complaining of physical ill-health.
      This study showed that 12% of the subjects had hypertension, 12%, gastritis or
      gastro-duodenal ulcer, 14%, allergic disease, and 19% miscellaneous diseases. 2)
      Of the subjects 62% had mental complaints and 31% mental ill-health. Depressive
      symptom was the most frequent mental complaint with 32% of the subjects diagnosed
      as DSM-III. The common diagnoses were adjustment disorders (19%), major affective
      disorders (6%), psychological factors affecting physical condition (5%) and
      dysthymic disorder (3%). Only one subject sought professional help from a
      psychiatrist for relief of mental complaints. The data suggest the severity of
      mental ill health in software engineers, but methodological limitations preclude
      a firm conclusion at this time. Further studies should be made on the mental
      health state in software engineers.

PMID- 1974659
TI  - [An inquiry into the factors affecting the complaints of subjective symptoms in
      VDT operators].
AB  - In a study of VDT workers the relationship between 1) their general life
      condition and working environment and 2) their eye, shoulder, neck, arm, waist
      and back complaints and their psychological symptoms was investigated. The
      subjects of the study were (147 workers whose age ranged from 18 to 39 years, and
      who had used VDT for a monthly average of more than 40 h. The results were as
      follows: 1) For most of the symptoms, a tendency was observed for females to
      complain more than males and for younger workers to complain more than the older
      workers. Neck, shoulder, arm, waist and back complaints were more common than
      psychological symptoms. These physical complaints appeared to be the most common
      among VDT workers. 2) The occurrence of eye-related symptoms is related to items
      directly affecting sight. This reaffirms the importance of illumination for the
      visual system. 3) This investigation showed that a relatively good VDT working
      environment was secured for the subjects of the present study. It is important
      that consideration be given to labor management such as provision of rest period
      and supervision.

PMID- 1974660
TI  - Pharmacological analysis of vasodilator responses to alpha 2-adrenoceptor
      agonists in isolated rat common carotid arteries.
AB  - Using the cannula inserting method, vasodilator responses to alpha 2-adrenoceptor
      agonists (clonidine, guanabenz, DJ7141 and xylazine) were investigated in
      isolated and perfused rat common carotid arteries. Alpha 2-adrenoceptor agonists
      dose-dependently induced a vasodilation in preparations preconstricted by
      noradrenaline. The potencies were in the order of clonidine greater than
      guanabenz greater than DJ-7141 greater than or equal to xylazine. Removal of the
      endothelium inhibited ACh-induced vasodilation, but not the alpha 2-agonist
      induced dilation. Atropine treatment inhibited ACh-induced vasodilation, but not
      the alpha 2-agonist-induced dilation. Alpha 2-agonist-induced dilations were not
      modified by beta-blockade, which significantly suppressed isoprenaline-induced
      vasodilations. The potent alpha 2-adrenoceptor antagonist DG5128 did not
      influence the alpha 2-agonist-induced vasodilation. In preparations
      preconstricted by PGF2 alpha, clonidine and xylazine never induced a
      vasodilation, and clonidine frequently induced vasoconstrictions that were
      completely blocked by bunazosin. It is concluded that alpha 2-adrenoceptor
      agonist-induced vasodilation is independent from the existence of the
      endothelium, and that it is not related to vascular beta- and alpha 2
      adrenoceptors and muscarinic receptors, suggesting that the alpha 2-adrenoceptor
      agonist-induced vasodilation is due to an antagonistic activity towards the
      vascular alpha 1-adrenoceptors.

PMID- 1974661
TI  - HLA extended haplotypes in steroid-sensitive nephrotic syndrome of childhood.
AB  - Idiopathic nephrotic syndrome has been postulated to have an immunopathogenic
      basis. To determine whether steroid-sensitive nephrotic syndrome is associated
      with greater than expected frequencies of specific extended haplotypes of the
      major histocompatibility complex, we studied genetic markers (Class I, II, III
      HLA alleles and glyoxalase I) in 173 subjects in 42 families of patients with
      nephrotic syndrome of childhood. The single allele, DQW2, was found in 72% of
      steroid sensitive patients compared with only 35% of the controls (P = 0.003). In
      half of 32 steroid sensitive, but not 10 steroid resistant, patients, one or both
      of two specific extended haplotypes (alleles that segregate together) were
      identified. The first, [HLA-A1, B8, DR3, DRW52, SCO1], occurred in 11 of 64
      haplotypes, or 17%, compared to 5% of controls (P = 0.017). The other, [HLA-B44,
      DR7, DRW53, FC31], occurred in 10 of 64 haplotypes, 16% compared to 3.8% of
      controls (P = 0.014). Five patients had both haplotypes. Patients with these
      specific extended haplotypes had a greater frequency of relapses than did those
      with other haplotypes. These data provide additional support for the hypothesis
      that steroid-sensitive nephrotic syndrome has an immunogenetic basis.

PMID- 1974662
TI  - Clonidine inhibits fluid absorption in the rabbit proximal convoluted renal
      tubule.
AB  - Previous studies have shown that norepinephrine (NE) and the beta-adrenoceptor
      agonist, isoproterenol (I), enhance fluid absorption (JV) in isolated, perfused
      proximal convoluted tubule segments (PCT). Pretreatment of PCT with the beta
      adrenoceptor antagonist, propranolol, inhibited the action of NE and produced a
      significant decline in JV, suggesting modulation of JV by both alpha- and beta
      adrenoceptors. The present studies further characterize the alpha-adrenoceptor
      control of JV in isolated perfused PCT using specific agonists and antagonists.
      Basal JV declined significantly with the addition of the alpha 2-adrenoceptor
      agonist, clonidine (10(-4) M), to the bath; however, it was unchanged with the
      addition of the alpha 1-adrenoceptor agonist, methoxamine (10(-6) or 10(-4) M).
      With the addition of 10(-6) M isoproterenol JV increased significantly, and
      returned to control values with the subsequent addition of clonidine (10(-6) or
      10(-4) M). Pretreatment of PCT with the alpha 2-adrenoceptor antagonist,
      yohimbine (10(-5) M), or with pertussis toxin (100 ng/ml) did not interfere with
      the stimulation of JV by isoproterenol, but abolished the inhibition of
      isoproterenol-stimulated JV by clonidine. Thus, clonidine inhibits JV in PCT via
      an alpha 2-adrenoceptor. This effect is mediated by a pertussis toxin inhibitable
      GTP-binding protein, but not one that is coupled to adenylyl cyclase.

PMID- 1974663
TI  - Male infertility in the hereditary polydactyly (PD) rat.
AB  - In the PD strain of rats, male pd homozygotes never sire, whereas male
      heterozygotes and female hetero- and homozygotes are fertile. In order to
      investigate the cause of infertility, pd/pd males were examined for their
      reproductive ability and gross and histological changes in the reproductive
      organs. Mating ability of pd/pd males was comparable to that of pd/+ males when a
      2 week cohabitation procedure was employed. Cryptorchidism, which is considered
      to be a cause of infertility, was observed in 63% of the 12 week old pd/pd males.
      However, this abnormality frequently was observed unilaterally and the incidence
      of bilateral cryptorchidism was only 13%. Although the relative weights of
      descended testes and epididymides were comparable between the pd/pd and pd/+
      males at 3 and 6 weeks of age, the values at 9 and 12 weeks of age were
      significantly lower in pd/pd males than in pd/+ males. A marked difference was
      not noted in relative weight changes of the seminal vesicles and prostate between
      the pd/pd and pd/+ males. Histological examination revealed defects in
      spermatogenesis in both descended and undescended testes in pd/pd males. The
      changes first appeared at 9 weeks of age and included vacuolation of nuclei of
      spermatocytes and spermatids, degeneration of spermatids, and occasionally
      multinucleated giant cells in the seminiferous tubules. In accessory sexual
      organs such as the epididymides, seminal vesicles, and prostate, no histological
      abnormalities were detected. These findings indicate that the substantial cause
      of infertility in pd/pd males is a disorder of spermatogenesis through which
      functionally normal spermatozoa are not produced.

PMID- 1974665
TI  - Physical and chemical considerations in the in vitro calibration of microdialysis
      probes for biogenic amine neurotransmitters and metabolites.
AB  - The object of the present study was to examine the effects of temperature,
      oxidation, and pH on in vitro relative recovery of catecholamine and indoleamine
      neurotransmitters and their metabolites using microdialysis probes. Relative
      recovery of norepinephrine (NE), dihydroxyphenylacetic acid (DOPAC), 5
      hydroxyindoleacetic acid (5HIAA), dopamine (DA), homovanillic acid (HVA), and 5
      hydroxytryptamine (5HT) increased with temperature from 0 to 46 degrees C. For
      each compound, the increase in the amount recovered with increasing temperature
      was different. The stability of norepinephrine and dopamine was not affected at
      any temperature using deoxygenated calibration standard solutions containing
      ascorbic acid but was greatly reduced when exposed to ambient air without
      antioxidant treatment; catecholamine metabolites and the indole compounds were
      less affected. No change for in vitro relative recovery was observed by varying
      the pH of the perfusing solution from 6 to 8. Thus, temperature control in probe
      calibration as well as analyte stability using antioxidant treatment are
      important in reducing the error when estimating extracellular concentrations of
      neurotransmitter and metabolites.

PMID- 1974664
TI  - Esmolol for treatment of intraoperative tachycardia and/or hypertension in
      patients having cardiac operations. Bolus loading technique.
AB  - Esmolol, administered as a bolus followed by continuous infusion, was used to
      treat the occurrence of transient tachycardia and hypertension or tachycardia
      alone before cardiopulmonary bypass in 45 patients. The study was conducted in
      two phases. Phase I (15 patients) was a dose-finding study and phase II (30
      patients) was a randomized, double-blind, placebo-controlled efficacy study. All
      patients received the last dose of their usual beta-adrenergic blocker the night
      before the operation and were anesthetized with midazolam, vecuronium, and
      enflurane in oxygen. Treatment criteria were either a systolic blood pressure
      greater than 140 mm Hg and a heart rate greater than 70 or a heart rate greater
      than 80 beats/min. In phase I, graduated doses of esmolol were given to
      successive patients. A dose of 80 mg followed by a 12 mg/min infusion was
      declared effective. Phase II patients were randomized to receive esmolol (n = 16)
      or placebo (n = 14). Hemodynamic data were collected at baseline and 1, 3, 5, and
      10 minutes after the administration of esmolol. Plasma norepinephrine was
      measured at baseline, 1, and 10 minutes. Esmolol significantly (p less than 0.05)
      reduced heart rate at 1, 3, 5, and 10 minutes but did not change blood pressure,
      pulmonary artery diastolic pressure, right atrial pressure, cardiac output, or
      systemic vascular resistance. Our results show that a bolus loading dose of
      esmolol is safe and effective in the treatment of tachycardia in patients with
      ischemic heart disease and that esmolol rapidly blocks the beta-adrenergic
      effects of norepinephrine associated with surgical stress.

PMID- 1974666
TI  - The current place of beta 2-agonists in the management of asthma.
AB  - Inhaled beta 2-stimulants are the most effective drugs for acute asthma attacks.
      This is probably due to the functional antagonism against a large variety of
      possible asthma mediators. A slight rebound increase of bronchial hyperreactivity
      12 to 23 h after stopping regular treatment has been proposed. This finding is
      not well documented and must be further studied. There is no convincing evidence
      that tachyphylaxis of clinical importance to the bronchodilating effect occurs in
      asthmatics receiving normal doses of beta 2-receptor stimulants but cannot be
      totally excluded. Candidates for regular inhaled beta 2-agonist treatment always
      have inflammation in their airways and should be given inhaled steroids. Steroids
      not only seem to reduce airway inflammation and hyperreactivity but they also
      reverse beta 2-receptor subsensitivity in experimental studies. Patients on
      purely prophylactic antiasthmatic drugs should be instructed always to carry
      their beta 2-stimulants inhalers.

PMID- 1974667
TI  - Approaches to a long-acting, selective beta 2-adrenoceptor stimulant.
AB  - Selected beta 2-stimulants were sought that would stick more firmly than
      salbutamol at their sites of action on the beta 2-adrenoceptor protein in the
      cell membrane. Of the substance synthesized and tested it was concluded that
      salmeterol represented a new class of beta 2-stimulants that because of their
      exceptionally long duration of action have potential clinical advantages over
      current available beta 2-stimulants in the treatment of asthma.

PMID- 1974668
TI  - The pharmacology of salmeterol.
AB  - The pharmacology of salmeterol hydroxynaphthoate (SALM) has been investigated in
      respiratory tissues in vitro and in animal models in vivo. In guinea pig trachea
      and human bronchial smooth muscle, SALM was more potent than isoprenaline (ISO),
      salbutamol (SALB), and clenbuterol (CLEN). The duration of action was greater
      than 7 h, whereas that for ISO, SALB, and CLEN was 2, 11, and 45 min,
      respectively. The sustained activity of SALM was reversed by sotalol, but was
      reestablished when the beta-blocker was removed. SALM was greater than 3000-fold
      weaker than ISO in cardiac tissues, indicating high beta 2-adrenoceptor
      selectivity. In the conscious guinea pig, aerosolized SALM, SALB, and CLEN caused
      dose-related bronchodilatation. The activity of SALM persisted for at least 6 h,
      compared with less than 2 h for SALB and CLEN. SALM is also a potent inhibitor of
      mediator release from human lung, this effect being sustained for up to 20 hours.
      In guinea pig airways in vivo, SALM inhibited histamine-induced plasma protein
      extravasation for approximately 8 h. Salmeterol is a potent and selective beta 2
      adrenoceptor agonist with a unique profile of action. It induces persistent
      bronchodilatation, sustained suppression of mediator release, and long-lasting
      inhibition of edema formation. This combination of properties may represent an
      important new advance in the treatment of bronchial asthma.

PMID- 1974669
TI  - Effect of antiasthma drugs on asthmatic reactions induced by toluene diisocyanate
      in sensitized subjects.
AB  - To determine the effect of antiasthma drugs on asthmatic reactions and airway
      inflammation, we studied several groups of sensitized subjects treated with
      active drugs or placebo before and after exposure to toluene diisocyanate in the
      laboratory. We observed that the steroidal anti-inflammatory agent prednisone,
      but not the nonsteroidal anti-inflammatory agent indomethacin, inhibits the late
      (but not the early) asthmatic reactions induced by TDI. Prednisone also inhibits
      the increase of bronchial responsiveness and the increase of neutrophils,
      eosinophils, and albumin in bronchoalveolar lavage fluid that are associated with
      late asthmatic reactions induced by exposure to TDI. Beclomethasone has a dose
      dependent inhibitory effect on TDI-induced late asthmatic reactions, whereas
      theophylline has a partial inhibitory effect on both early and late asthmatic
      reactions, and verapamil, ketotifen, cromolyn. Beta 2-adrenergic agonists have
      variable effects: salbutamol has no effect on early and late asthmatic reactions
      by itself, but it potentiates the inhibitory effect of low doses of
      beclomethasone. Broxaterol inhibits early asthmatic reactions, but has no effect
      on the late asthmatic reactions and the associated inflammatory response. These
      results suggest that, in sensitized subjects, late asthmatic reactions induced by
      toluene diisocyanate can be prevented by steroidal anti-inflammatory agents,
      whereas early asthmatic reactions may be prevented either by an association of
      inhaled steroids and beta-adrenergic agonists, or by beta-adrenergic agonists
      (e.g., broxaterol) with more complex mechanisms of action.

PMID- 1974672
TI  - Risk/benefit ratio of long-term treatment with beta 2-adrenoceptor agonists.
AB  - Optimal control of chronic obstructive airway disorders is usually achieved with
      therapy based on beta 2-adrenoceptor agonist administration. Aerosols are highly
      effective, have few side effects, allow for fine adjustment of dosage to titrate
      symptoms, and result in reduction in hyperreactivity. Equivalent bronchodilating
      doses of oral agents cause side effects that limit acceptability. With oral
      agents, cardiohemodynamic disturbances are usually minor, while tremor and
      restlessness diminish with continued drug use. In chronic regimens, an aerosol
      beta 2-adrenergic agent should be chosen whose overall incidence of side effects
      is less than 5%, and an oral agent that produces no more than a 10% incidence of
      tremor. Suboptimal oral dosages in combination with maximal dosages of beta 2
      agonist aerosol, with or without other bronchodilator drugs, are advisable for
      chronic therapy. An optimal risk/benefit ratio with broxaterol therapy will
      probably be achieved by using an aerosol-oral combination. Thus, broxaterol, a
      new beta 2-agent, should be studied further to determine its value in chronic
      bronchospastic disorders.

PMID- 1974673
TI  - Beta-agonistic properties of tulobuterol, a new beta-sympathicomimetic drug, and
      its effects on pulmonary beta-adrenoceptor characteristics.
AB  - Radioligand binding studies have been developed to determine pharmacologic
      receptor characteristics in vitro. With this assay, not only the number and
      dissociation constant (KD) can be studied, but also the interaction of agonists
      with the receptor. We used this method to study a new beta 2-sympathicomimetic
      drug, tulobuterol (1-(0-chlorophenyl)-2-butylamino-ethanol hydrochloride). Two
      sets of experiments were performed. One set of experiments investigated the
      effects of tulobuterol and terbutaline in chronic administration, while the
      second set compared the beta-adrenoceptor-stimulating properties of tulobuterol
      with terbutaline and salbutamol. The effects of 10 days' administration of
      tulobuterol and terbutaline on beta-adrenergic characteristics in rats were
      assessed biochemically by means of radioligand binding studies on pulmonary
      membranes and functionally using isolated tracheal spirals. It was found that:
      (1) In vivo treatment with both drugs induced a reduction of the number of beta
      adrenoceptors bound by 3H-dihydroalprenolol (3H-DHA); however, tulobuterol also
      induced an increased affinity for beta-adrenoceptor binding. (2) Tulobuterol
      induced a significant increase in the sensitization of tracheal smooth muscle,
      facilitating the relaxation of airway smooth muscle. The inhibition of 3H-DHA
      binding with the three drugs was best fit in a two-binding site model, showing
      high- and low-affinity binding sites. The high-affinity sites had similar KD
      values for terbutaline and tulobuterol (1.6 x 10(7) and 1.5 x 10(-7),
      respectively). The high-affinity sites for salbutamol had a higher KD value (9.4
      x 10(-7), suggesting a lower affinity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1974670
TI  - Pharmacology of airway inflammation in asthma.
AB  - Chronic desquamative eosinophilic bronchitis is a characteristic pathologic
      feature of asthma which may even antedate the onset of symptoms. The pharmacology
      of asthmatic inflammation has been relatively poorly studied and most of the
      current data available have been inferred indirectly from studies of bronchial
      hyperresponsiveness and late-phase responses. Apart from mast cells, the effects
      of drugs used in the treatment of asthma on other airway inflammatory cells such
      as eosinophils, alveolar macrophages, etc. have not been extensively studied. The
      pharmacology of asthmatic inflammation should comprise the study of various
      aspects of this inflammatory response such as airway microvascular leakage,
      mediator release, and cell chemotaxis. Ultimately the pharmacologic modulation of
      the pathologic features of the asthmatic airway by the chronic use of antiasthma
      drugs, coupled with clinical responses, need to be investigated using bronchial
      biopsies and broncholveolar lavage in asthmatic patients.

PMID- 1974671
TI  - Long-term management of reversible obstructive airways disease in adults.
AB  - The goals of the long-term management of reversible obstructive airways disease
      (ROAD) are to find the minimum treatment that controls symptoms, allows
      resumption of normal life, prevents severe attack and death, and controls airflow
      obstruction. ROADs include asthma, chronic bronchitis, and emphysema. Although
      the differential diagnosis between these different entities may be difficult,
      they share the same possibilities of pharmacotherapy, including bronchodilator
      and antiinflammatory drugs. beta 2-agonists administered via inhaled route
      produce the best bronchodilator/side effects ratio, provided that the drugs reach
      the bronchi. This underlines the importance of a proper inhalation technique when
      using a metered-dose inhaler. In patients with hand-breath coordination problems,
      powder inhalers or spacer devices are useful to ameliorate the therapeutic
      efficacy of inhaled drugs. Anticholinergic agents are usually less potent
      bronchodilators than inhaled beta 2 agonists in asthma, but they may have
      additive effects when associated with beta 2 agonists. Only a therapeutic trial
      with peak-flow monitoring can demonstrate the efficacy of anticholinergic drugs
      in individuals. Theophylline's kinetics are characterized by a narrow therapeutic
      index with high inter- and intraindividual variabilities. Sodium cromoglycate and
      nedocromil sodium are antiallergic drugs, the efficacy of which has been
      demonstrated in controlled studies. Corticosteroids are the most efficient anti
      asthma drugs. Inhaled corticosteroid dosing should be tailored to each
      individual. If inhaled corticosteroid therapy is used in an oral corticosparing
      attempt, patients should be followed-up during several months. The management of
      ROAD includes the diagnostic procedures, the identification of triggers and
      inducers of airways obstruction, the assessment of severity of the disease, and
      then the treatment and education of the patient. Strategy design to achieve
      proper use of drugs by patients is discussed.

PMID- 1974674
TI  - Basic pharmacology of new long-acting sympathomimetics.

PMID- 1974675
TI  - Can a new beta 2-agonist reduce the mortality of asthma?
AB  - Tulobuterol is a synthetic beta-adrenergic agonist which, when administered
      orally, is a potent, long-acting bronchodilator. The safety and efficacy of 2 mg
      tulobuterol tablets taken twice daily was compared to that of 4 mg salbutamol
      tablets taken three times daily for a period of 12 weeks in outpatients with
      stable chronic asthma in a randomized, double-blind, multi-center study conducted
      in Australia. Strict entry criteria were employed; only those patients whose
      baseline FEV1 value was between 40-70% of the predicted normal value and
      increased at least 20% after two inhalations of a metered dose (250 micrograms
      per dose) of terbutaline aerosol at a screening visit were included. Treatment
      with active study drug was preceded by a 2 week single-blind, placebo lead-in
      period. The onset and duration of the bronchodilating effect was studied on the
      first day of the placebo lead-in period and on the first and last days of the 12
      week parallel design treatment period. Of 140 patients enrolled, 73 had
      tulobuterol and 67 had salbutamol. Of these, 61 tulobuterol and 59 salbutamol
      treated patients could be evaluated for efficacy. Of the 140 patients, 129
      completed the study. All patients were issued a mini peak flow meter and diary
      cards to record daily PEFRs and symptoms of airways obstruction throughout the
      study. The demographics of the patients in both treatment groups were similar in
      all modalities: they were comparable in age, duration of asthma, mean FEV1
      (expressed as percent of predicted normal), and reversibility (as demonstrated by
      an increase in FEV1 after administration of a beta 2-agonist aerosol).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1974676
TI  - Effects of a combined treatment theophylline and tulobuterol on nocturnal chronic
      asthma.

PMID- 1974677
TI  - Acute and long-term effectiveness of tulobuterol inhaler, a new beta 2-agonist,
      in the treatment of asthma.
AB  - Two separate studies were conducted to evaluate the efficacy and safety of
      tulobuterol and the development of tachyphylaxis, if any, after prolonged use.
      The first, a double blind, crossover study, compared the efficacy and safety of
      tulobuterol aerosol 400 micrograms tid and salbutamol aerosol 200 micrograms tid
      in 38 patients with reversible obstructive airways disease. Each study period
      lasted 4 weeks, separated by a one week washout period. Evaluation of efficacy
      was performed on day 1 by monitoring spirometric values up to 6 hours postdosing.
      Additionally, changes in baseline pulmonary function were evaluated by measuring
      FEV1, FVC and PEFR at each weekly visit. Twenty-nine patients were evaluable.
      Tulobuterol was shown to be as effective as salbutamol in onset, peak, and
      duration of response. Mean increases in FEV1 after tulobuterol ranged from 22% at
      5 minutes postdose to 30% at 1 hour postdose; a clinically significant mean
      increase of 24% was recorded after 3 hours. In comparison, mean increases for
      salbutamol were 24% at 5 minutes postdose and 31% at 1 hour postdose; after 3
      hours the mean increase was 21%. Statistically significantly greater increases in
      mean baseline FEV1 were recorded in favor of tulobuterol. Following 2 weeks of
      each treatment, tulobuterol showed a mean increase of 14%, compared to a mean
      postsalbutamol increase of 12%. After 4 weeks, differences were again
      statistically significant, with tulobuterol showing a mean increase in baseline
      FEV1 of 17% compared to 3% for salbutamol. Tulobuterol treatment was associated
      with smaller changes in blood pressure and pulse rate than salbutamol.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1974678
TI  - Two-month comparative study of tulobuterol aerosol versus fenoterol aerosol in
      patients with chronic obstructive lung disease.
AB  - In this two month, double-blind, crossover study, the efficacy and safety of
      tulobuterol aerosol (400 micrograms qid) was compared to fenoterol aerosol (400
      micrograms qid) in patients with chronic obstructive lung disease. Thirty-six
      (36) adults with reversible bronchospasm were enrolled. All patients were
      evaluable. On set of response was within 5 minutes for both drugs. Mean increases
      in FEV1 were greater after tulobuterol than fenoterol at every time interval.
      Increases peaked at 30-60 minutes postdose. Duration of response was longer after
      tulobuterol with mean FEV1 remaining greater than 15% over baseline for at least
      6 hours postdose. Mean predose FEV1 values were significantly greater after 2 and
      4 weeks of tulobuterol treatment compared with fenoterol. Despite these large
      increases, changes in mean FEV1 from predose to 1 hour postdose at these visits
      were not significantly different between treatment groups. Results of
      plethysmography testing also indicated greater improvement after tulobuterol. In
      addition, improvement in pulmonary symptoms was more pronounced during
      tulobuterol therapy. Small changes in mean blood pressure occurred, with greater
      changes after fenoterol than after tulobuterol. Changes in mean pulse rate were
      significantly greater following fenoterol administration. No adverse reactions
      were reported during tulobuterol treatment; however, one patient experienced
      severe tremor, tachycardia, and sweating during fenoterol treatment and withdrew
      from the study prematurely. The results in this study indicate that tulobuterol
      aerosol is more effective than fenoterol aerosol in the treatment of patients
      with chronic obstructive lung disease, with fewer cardiovascular effects and no
      adverse reactions.

PMID- 1974679
TI  - Prolonged treatment with oral and inhaled tulobuterol does not induce airways
      tachyphlaxis.
AB  - Beta 2-agonists have been shown to induce beta 2-adrenoceptor downregulation in
      vivo and in vitro. Whether this has any functional relevance remains unclear.
      Tulobuterol is a new synthetic beta 2-agonist with potent and prolonged
      bronchodilator activity when given by oral and inhaled routes. The effect of
      tulobuterol aerosol (400 micrograms q.i.d.) and tulobuterol tablets (2 mg b.i.d.)
      was studied in patients with chronic asthma and reversible airways obstruction in
      two separate trials. Tulobuterol produced significant bronchodilatation after the
      first and final dose over a 6-h period and the effects were comparable. The
      bronchodilator activity of tulobuterol given by inhalation and oral routes was
      not attenuated after 6 months of continuous treatment. There was significant
      improvement in symptom score and lung function measurements. Side effects,
      predominantly tremors, were observed at the start of treatment with tablet
      formulation but the incidence and severity of tremors decreased after 6 months.
      The changes in BP and pulse rate were not clinically significant. These results
      confirm the potent bronchodilator activity of tulobuterol and the lack of
      tachyphylaxis after prolonged treatment.

PMID- 1974680
TI  - Long-term studies on long-acting sympathomimetics.
AB  - Long-term treatment studies with formoterol and salmeterol show that these
      inhaled long-acting beta 2-agonists compared to available beta 2-agonists produce
      better bronchodilation, decrease the need for additional doses, decrease asthma
      symptoms, and are strongly preferred by the patients. Development of tolerance
      has not been found. One case history indicates that these effective
      bronchodilators might mask deterioration of asthma.

PMID- 1974681
TI  - Treatment considerations in children aged 0-5 years.
AB  - Children in the first year of life have a less satisfactory response to
      treatment, but it is still worthwhile using bronchodilators by oral or nebulized
      route. In more severe cases, cromolyn or nebulized steroids are needed. Over 1
      year, response to therapy is better and metered-dose inhalers with spacers become
      an easier way to deliver medication, although in severe acute attacks the
      nebulized route remains the preferred one.

PMID- 1974682
TI  - The role of neurotransmitters in bronchial asthma.
AB  - Neural control of airway caliber is far from simple and it is likely to
      contribute to the airway narrowing in asthma and chronic obstructive airway
      disease (COAD). Complex interactions may occur between the different components
      of autonomic control and inflammatory mediators released from cells in the
      inflamed airway may profoundly alter the balance of neural control. Further
      elucidation of these interactions should shed light on the mechanisms of airway
      disease and may lead to therapeutic advances.

PMID- 1974683
TI  - Inhalation delivery of asthma drugs.
AB  - In the immediate future, metered-dose inhalers (MDIs) with spacers remain the
      aerosol application of choice for topical steroids, mainly to reduce side
      effects. For beta 2-agonist, anticholinergics and prophylactic drugs, MDI (with
      or without demand valve), dry powder inhalers (multidose inhalers), ultrasonic or
      jet aerosol generators (with or without mechanical breathing assistance [IPPB])
      are chosen according to the preference or the ability of the patients to perform
      the necessary breathing maneuvers as well as the availability of different
      products in different countries.

PMID- 1974684
TI  - Bronchial asthma and the role of beta 2-agonists.
AB  - Asthma is defined as reversible airflow obstruction; the mechanism for this
      airflow obstruction is considered to be caused by a combination of an
      inflammatory process leading to a thickened edematous airway lining and bronchial
      smooth muscle constriction. The identification of specific beta-receptors in the
      autonomic system led to the development in the early 1960s of selective beta 2
      agonists with their precise effects on the bronchial smooth muscle without direct
      action on cardiac muscle. The early beta 2-agonists such as salbutamol have a
      comparatively short bronchodilator action but a rapid onset of action, making
      them useful as "rescue" bronchodilators. Regular beta 2-agonists alone may mask
      the underlying pathogenesis of asthma and may be associated with tachyphylaxis or
      rebound bronchial hyperreactivity. The observation that a thickened airway lining
      may lead to disproportionate increases in airways resistance with small changes
      in bronchial muscle shortening suggests beta 2-agonists should be given in
      conjunction with anti-inflammatory therapy. With their long duration of action
      but slow onset the new beta 2-agonists may have a role in prophylaxis of asthma
      rather than rescue bronchodilation.

PMID- 1974685
TI  - Characteristics of bronchodilating activity of formoterol.
AB  - Formoterol possesses a chemical structure characterized by an NH group attached
      to the benzene ring and an important side chain. This characteristic may explain
      its long-lasting effects observed in animal and humans. Formoterol is as active
      as salbutamol in terms of maximum improvement of FEV1 and its bronchodilating
      effect is observed at all levels of the bronchial tree.

PMID- 1974687
TI  - Multicenter 1-year trial on formoterol, a new long-acting beta 2-agonist, in
      chronic obstructive airway disease.
AB  - An open multicenter trial was performed in 242 subjects with chronic obstructive
      airways disease between August 1987 and April 1989. Two hundred thirty-six
      subjects were evaluated with regard to safety (m 137, f 99, mean age 49.4 (18-77)
      years) and 204 subjects with regard to therapeutic efficacy (m 120, f 84, mean
      age 49.2 (18-77) years). Twelve micrograms (one puff) formoterol was given by
      metered-dose inhaler twice daily. Investigations were performed at days 0, 14,
      and subsequently in monthly intervals. Twenty-one patients (10.3%) were
      sufficiently treated by formoterol alone. One hundred and eighty-three (89.7%)
      required additional medication, which could be reduced in 90 cases (45.6%).
      Initially symptoms were present in 201 of 204 patients. At 1 year, 43 patients
      (21.1%) were symptom-free. At day 0 32.4% of the patients felt "very good" or
      "good." At 1 year the rate increased to 68.1%. Raw decreased from 0.52 +/- 0.26
      (0.06-2.11) kPa.L-1.S at day 0 to 0.33 +/- 0.14 (0.06-0.88) kPa.L-1.S (= -43.5%)
      at 1 year. FEV1 increased from 1.90 +/- 0.80 to 2.54 +/- 0.97 L (33.7%). The
      global assessment of therapeutic efficacy was classified as "very good" in 51%
      (patients) and 47% (doctors), respectively, and as "good" in 38.7% and 42.0%,
      respectively. Tolerability was "very good" in 82.3% (patients, doctors), and
      "good" in 12.7% (patients) or 13.7% (doctors). The treatment did not influence
      blood pressure or heart rate. Twenty-nine patients (12.3% of 236) reported
      unwanted 39 side effects, such as tremor (6.36%), headache (2.54%), dryness of
      the mouth (1.27%), cough (0.85%), and dizziness (0.85%).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1974686
TI  - Long-term efficacy of formoterol compared to salbutamol.
AB  - In a randomized, double-blind, between-patient, multicenter study in 301 patients
      with ROAD, the efficacy and tolerability of the new long-acting selective beta 2
      sympathicomimetic drug formoterol (12 micrograms inhalation b.i.d.) was compared
      with salbutamol (200 micrograms inhalation q.i.d.). There was no statistically
      significant (s.s.) difference in acute reversibility and long-term efficacy of
      both drugs, measured by the point in time of expected maximal effect. However,
      formoterol had a highly s.s. longer duration of action than salbutamol, as shown
      by peak expiratory flow (PEF) measurements: the overall mean morning PEF in the
      formoterol group was 341 L/min. 14 h after the last taken dose and in the
      salbutamol group this measure was 304 L/min 9 h after the last dose. The patients
      taking formoterol had s.s. less asthma attacks and needed s.s. less rescue
      medication than those taking salbutamol. In the global assessment of efficacy,
      formoterol was accepted as being s.s. better ("very good" + "good": 76%) than
      salbutamol ("very good" + "good": 50%). The tolerability of each drug, as
      reflected by adverse reactions and global assessment, was equally good in both
      groups. Ninety-one percent of the patients in the formoterol group wanted to
      receive the same drug again versus 79% in the salbutamol group.

PMID- 1974689
TI  - Formoterol, a new long-acting selective beta 2-agonist, decreases airway
      responsiveness in children with asthma.
AB  - We compared the protective effect and duration of action of inhaled formoterol
      with salbutamol and placebo in 16 asthmatic children in a double-blind, cross
      over study. All had an FEV1 greater than or equal to 70% predicted normal and a
      provocative concentration of methacholine (MCh) required to decrease their FEV1
      by 20% (PC20) less than or equal to 4 mg/ml. On each study day, FEV1 was within
      10% and PC20 within one doubling-dose of the initial visit. Patients received
      either placebo, salbutamol 200 micrograms, formoterol 12 micrograms, or
      formoterol 24 micrograms by metered-dose inhaler. FEV1 and PC20 were measured
      repeatedly over 12 h. After salbutamol, peak FEV1 was 120% of baseline at 30 min
      and returned to baseline in 3 h. After formoterol (12 or 24 micrograms) peak FEV1
      was 118% at 3 h and remained above baseline for at least 12 h. Protection from
      MCh by both doses of formoterol was significantly better than by salbutamol.
      Protection from formoterol 12 and 24 micrograms at 12 h was equivalent to that
      from salbutamol at 3 h. The PC20 of four children 48 h after formoterol 24
      micrograms was more than twice their baseline PC20. Formoterol by inhalation is
      potent and long-acting and provides significantly better antiasthma protection
      than salbutamol.

PMID- 1974688
TI  - Efficacy of formoterol metered aerosol in children.
AB  - To evaluate the effect of formoterol MDI (F) in the treatment of bronchial
      childhood asthma, five studies were performed in a total of 66 young asthmatics.
      In single-dose studies with 12 micrograms, F showed a rapid onset of action and
      in comparison to salbutamol a four-times-longer-lasting bronchospasmolytic effect
      (BSL). In addition, we looked at the BSL and the protective effect (P) in
      exercise-induced asthma (EIA) after 6, 12, and 24 micrograms. The BSL was not
      significantly different with respect to onset, magnitude, and duration of action,
      nor was the P, yet the latter seemed to be superior at 2 and 8 h after 24
      micrograms. In a long-term study with 2 X 12 micrograms the patients' clinical
      well-being could be improved while drug consumption decreased. During another 3
      month monotherapy with 2 X 12 micrograms the P in histamine- and cold air
      challenge was investigated and compared to prestudy values. It could be shown
      that long-lasting BSL and P did not diminish. Furthermore, there is evidence to
      suggest an improvement of bronchial hyperresponsiveness after withdrawal of F.

PMID- 1974691
TI  - Chloroplast DNA evolves slowly in the palm family (Arecaceae).
AB  - A survey of cpDNA restriction-site variation for 22 species representing five of
      the six subfamilies of the palm family was conducted. Phylogenetic
      reconstructions based on the restriction-site data are in general agreement with
      conventional analyses based on morphological characters. Base-substitution
      estimates, derived from the restriction-site data, indicate a potential 5-13-fold
      decrease in substitution rates within the palms relative to rate estimates for
      annual plant taxa. Approximately 1,000 bp of the rbcL gene (ribulose-1,5
      bisphosphate carboxylase, large subunit) were sequenced from species representing
      two subfamilies of the palms. The complete DNA sequence data are in accord with
      the restriction-site data and indicate a total rate of nucleotide substitution
      that is about eightfold lower than that observed for annual plants.

PMID- 1974690
TI  - [Genetic analysis of Friedreich's ataxia using polymorphic DNA markers].
AB  - Friedreich's ataxia (FA) is a progressive degenerative disease involving both
      central and peripheral nervous system. It is an autosomal recessive hereditary
      disorder, which begins around puberty and has an unknown genetic basis and
      biochemical defect. The recent mapping of FA locus in human chromosome 9 by means
      of the analysis of the molecular genetic linkage has permitted to evaluate FA
      genetics with polymorphic genetic markers (RFLPs) that are secreted linked with
      the FA gene. The normal and mutant allele secretion of FA was evaluated in ten
      Spanish families with one or two members with FA by means of several cloned
      probes (MCT112, DR47, D9S1 and HHH220), localized in chromosome 9 and strongly
      linked to FA gene, with the aim of achieving a predictive diagnosis of relatives
      in the pediatric age and to detect healthy carriers. In 9 out of 10 families some
      totally or partially informative RFLP were found. In 5 of 6 relatives in
      pediatric age the future development of the disease could be ruled out. By
      contrast, the carrier status could only be identified in three relatives. In a
      family with two affected children a genetic recombinant for D9S1 was found.
      Remarkably, one of them had a better clinical evolution and preserved tendon
      reflexes in lower limbs.

PMID- 1974692
TI  - Evidence for rolling-circle replication in a major satellite DNA from the South
      American rodents of the genus Ctenomys.
AB  - A major PvuII satellite DNA has been cloned from a South American octodontid
      rodent of the genus Ctenomys (C. porteousi). The satellite monomer, termed RPCS,
      is 337 bp in size and 42% G + C. Analysis of the nucleotide sequence demonstrates
      that RPCS is not composed of a series of shorter repeats. RPCS-related sequences
      were found in 11 of 12 Ctenomys species analyzed by hybridization under high
      stringency conditions. The only negative species, C. opimus, was reactive under
      low-stringency conditions. RPCS-related sequences were not found under high- or
      low-stringency conditions in Calomys musculinus and Mus musculus. However, under
      low-stringency conditions, RPCS-related sequences were found in the octodontid
      Octodontomys gliroides, which is thought to have diverged from the genus Ctenomys
      more than 10 Myr ago. The pattern of periodicities observed, by restriction
      analysis, between Ctenomys species in the satellite array can be mainly accounted
      for by a rolling-circle amplification mechanism but cannot be solely accounted
      for by unequal crossing-over.

PMID- 1974693
TI  - The analysis of population survey data on DNA sequence variation.
AB  - A technique is presented for the partitioning of nucleotide diversity into within
      and between-population components for the case in which multiple populations
      have been surveyed for restriction-site variation. This allows the estimation of
      an analogue of FST at the DNA level. Approximate expressions are given for the
      variance of these estimates resulting from nucleotide, individual, and population
      sampling. Application of the technique to existing studies on mitochondrial DNA
      in several animal species and on several nuclear genes in Drosophila indicates
      that the standard errors of genetic diversity estimates are usually quite large.
      Thus, comparative studies of nucleotide diversity need to be substantially larger
      than the current standards. Normally, only a very small fraction of the sampling
      variance is caused by sampling of individuals. Even when 20 or so restriction
      enzymes are employed, nucleotide sampling is a major source of error, and
      population sampling is often quite important. Generally, the degree of population
      subdivision at the nucleotide level is comparable with that at the haplotype
      level, but significant differences do arise as a result of inequalities in the
      genetic distances between haplotypes.

PMID- 1974694
TI  - p-[125I]iodoclonidine is a partial agonist at the alpha 2-adrenergic receptor.
AB  - The binding properties of p-[125I]iodoclonidine [( 125I]PIC) to human platelet
      membranes and the functional characteristics of PIC are reported. [125I]PIC bound
      rapidly and reversibly to platelet membranes, with a first-order association rate
      constant (kon) at room temperature of 8.0 +/- 2.7 x 10(6) M-1 sec-1 and a
      dissociation rate constant (koff) of 2.0 +/- 0.8 x 10(-3) sec-1. Scatchard plots
      of specific [125I]PIC binding (0.1-5 nM) were linear, with a Kd of 1.2 +/- 0.1
      nM. [125I]PIC bound to the same number of high affinity sites as the alpha 2
      adrenergic receptor (alpha 2-AR) full agonist [3H] bromoxidine (UK14,304), which
      represented approximately 40% of the sites bound by the antagonist [3H]yohimbine.
      Guanosine 5'-(beta, gamma-imido)triphosphate greatly reduced the amount of
      [125I]PIC bound (greater than 80%), without changing the Kd of the residual
      binding. In competition experiments, the alpha 2-AR-selective ligands yohimbine,
      bromoxidine, oxymetazoline, clonidine, p-aminoclonidine, (-)-epinephrine, and
      idazoxan all had Ki values in the low nanomolar range, whereas prazosin,
      propranolol, and serotonin yielded Ki values in the micromolar range. Epinephrine
      competition for [125I]PIC binding was stereoselective. Competition for
      [3H]bromoxidine binding by PIC gave a Ki of 1.0 nM (nH = 1.0), whereas
      competition for [3H]yohimbine could be resolved into high and low affinity
      components, with Ki values of 3.7 and 84 nM, respectively. PIC had minimal
      agonist activity in inhibiting adenylate cyclase in platelet membranes, but it
      potentiated platelet aggregation induced by ADP with an EC50 of 1.5 microM. PIC
      also inhibited epinephrine-induced aggregation, with an IC50 of 5.1 microM. Thus,
      PIC behaves as a partial agonist in a human platelet aggregation assay. [125I]PIC
      binds to the alpha 2B-AR in NG-10815 cell membranes with a Kd of 0.5 +/- 0.1 nM.
      [125I]PIC should prove useful in binding assays involving tissues with a low
      receptor density or in small tissue samples and in studies of cloned and
      expressed alpha 2-AR.

PMID- 1974695
TI  - Generation of chromosome size polymorphism during in vivo mitotic multiplication
      of Plasmodium berghei involves both loss and addition of subtelomeric repeat
      sequences.
AB  - Extensive chromosome size polymorphism arises in Plasmodium berghei during in
      vivo mitotic multiplication. Size differences between homologous chromosomes
      involve rearrangements occurring in the subtelomeric portions while internal
      chromosomal regions do not contribute significantly to chromosome size
      polymorphism. Differences in the copy number of a 2.3-kb subtelomeric repeated
      unit are shown to correlate with size variations, and in at least one case to
      account completely for the size difference between two variants of the same
      chromosome.

PMID- 1974696
TI  - Astemizole-induced paresthesia.

PMID- 1974697
TI  - A therapy against vasospasm after subarachnoidal haemorrhage: clinical experience
      of balloon angioplasty.
AB  - Vasospasm is a phenomenon often present in human cases after subarachnoidal
      haemorrhage. Its aetiology and pathophysiology are unknown. As a result, cases of
      vasospasm do not respond to any known pharmacological therapy. We present in this
      paper, a practical application of intravascular surgery for vasospasm. In this
      procedure the requirement for a portable digital subtraction unit, transcranial
      Doppler sonography, and being able to determine quickly the neurological state of
      the patient are very important points. The use of monitoring equipment is
      especially indispensable during the carrying out of percutaneous transluminal
      angioplasty (PTA), which should be performed as soon as possible after the
      occurrence of vasospasm. The case of a 54-year-old male patient suffering from a
      ruptured anterior cerebral artery aneurysm was studied. Neck clipping was
      performed on the second day. On the fifth day the neurological state was stupor,
      and transcranial Doppler sonography (TCD) revealed a flow velocity of over 100 cm
      s-1. PTA was performed on the sixth day. The bilateral middle cerebral artery was
      dilated and the flow velocity slowed to within the normal range. The neurological
      state improved to clouding of consciousness after PTA. On the eighteenth day, the
      patient's consciousness and bilateral carotid angiograms revealed the vessels to
      be dilated still. It was concluded that PTA therapy, and the use of a portable
      digital subtraction unit and TCD sonography, for vasospasm caused by
      subarachnoidal haemorrhage is useful and effective.

PMID- 1974698
TI  - In vivo 31phosphorus spectroscopy during transient cerebral ischaemia in the
      gerbil.
AB  - The depletion of the high energy phosphates; phosphocreatine and ATP, during
      cerebral ischaemia disrupts normal cellular function and can lead to cerebral
      infarction. Using in vivo nuclear magnetic resonance spectroscopy, the metabolic
      effects of the gerbil model of transient bilateral carotid artery occlusion were
      quantified. By examining the changes in the inorganic phosphate (Pi),
      phosphocreatine (PCr) and beta-ATP peaks, the PCr/Pi ratio, the PCr/beta-ATP
      ratio and intracellular pH (pHi) before, during and after an ischaemic insult
      were calculated. Preischaemic values for these parameters were: PCr/Pi = 2.466 +/
      0.130, PCr/beta-ATP = 1.691 +/- 0.053, pHi = 7.112 +/- 0.021. By the end of 20
      min of global ischaemia, the PCr and beta-ATP peaks fell to levels similar to
      background in most animals. Calculated values were: PCr/Pi = 0.488 +/- 0.126,
      PCr/beta-ATP = 1.833 +/- 0.179, pHi = 6.551 +/- 0.258. With reperfusion, PCr/Pi
      increased rapidly back towards preischaemic levels but pHi improvement was
      delayed 10 min after that of PCr/Pi. By 1 h of reperfusion, both PCr/Pi and pHi
      were statistically equivalent to preischaemic values. During ischaemia, ATP was
      lost more rapidly than the storage form, PCr, but recovery of both was parallel.
      This suggested an intact ability to store such energy. These data indicate that
      the gerbil brain recovers normal high energy phosphate levels within an hour
      following a 20 min ischaemic insult, but that initial reperfusion does not
      immediately correct intracellular acidosis. Such a delay may prove a useful
      marker of those animals with more severe ischaemic injury.

PMID- 1974699
TI  - High-dose methylprednisolone and 'ex vivo' release of eicosanoids after
      experimental subarachnoid haemorrhage.
AB  - In the present study we have investigated the effects of high-dose
      methylprednisolone (MP) treatment on the 'ex vivo' release of four major
      eicosanoids in an experimental model of subarachnoid haemorrhage (SAH) with the
      aim of verifying: (a) the efficacy in reducing arachidonic acid metabolism
      enhancement; (b) whether high-dose methylprednisolone is effective on both the
      cyclooxygenase and lipoxygenase pathways; and (c) discussing the possible role of
      high-dose MP treatment in brain protection after SAH. Levels of prostaglandin D2
      and E2, prostacyclin and also leukotriene C4 were determined by the
      radioimmunoassay technique after 1 h incubation of cerebral cortex samples of
      rats which had been subjected to experimental SAH procedure (injection of 0.3 ml
      of autologous arterial blood). The release of prostaglandin D2 at 48 h after SAH
      is significantly higher when compared to that of sham-operated animals (P less
      than 0.01); prostaglandin E2 release is significantly enhanced at 6 h after the
      SAH procedure (P less than 0.01); release of the lipoxygenase metabolite is
      significantly enhanced at 1, 6 and 48 h after SAH induction; MP significantly
      decreases the release of all eicosanoids, and values in treated animals do not
      differ from those of sham-operated animals. The results of the present study
      suggest that the global inhibitory effect of high-dose MP treatment on the 'ex
      vivo' release of eicosanoids after experimental SAH could be considered to be one
      of the neurochemical correlates for the reduced incidence and severity of
      arterial inflammatory response, which results in chronic vasospasm and supports
      the clinical evidence of MP efficacy in preventing or reducing the incidence of
      arterial vasospasm after aneurysmal rupture.

PMID- 1974701
TI  - Brain tissue elasticity and CSF elastance.
AB  - In the analysis of the pressure-volume relationship of the intracranial system,
      the concept of brain elastance, sometimes called tissue elastance or CSF
      elastance, is often used. It is generally designated as Ecsf and is calculated as
      the slope of the pressure-volume curve of the system. Variations in Ecsf are
      related to, for example, changes in the buffering capacity of the system which,
      however, could be influenced by the cerebral vascular volume, compressibility of
      the meningeal membranes, and compressibility of the subpial brain tissue. Our
      interest is in isolating the effect of controlled changes in the intracranial
      system with changes in the subpial tissue only. Here we discuss the measurement
      of brain tissue elasticity and describe two experimental conditions in which
      simultaneous measurements showed distinct differences between the behaviour of
      the system CSF elastance and brain tissue elastic behaviour.

PMID- 1974700
TI  - Habenular neuron responses to noxious input are modified by dorsal raphe
      stimulation.
AB  - Single-cell experiments were undertaken to characterize the neurons of the rat
      habenular complex (Hab) which respond to noxious input and the extent to which
      the noxious responses can be modulated by dorsal raphe stimulation. The reported
      observations demonstrate that habenular neurons exhibit two response patterns to
      noxious stimulation termed 'nociceptive-on' and 'nociceptive-off'. In addition,
      it was demonstrated that dorsal raphe stimulation modulates the noxious input to
      the 'nociceptive-on' and to the 'nociceptive-off' cells. These findings
      demonstrated that the habenular complex responds to noxious input and, together
      with other findings reporting that both direct morphine application into the Hab
      and electrical stimulation of the Hab produced analgesia, suggest that the
      habenular complex is integrated into the pain regulatory circuitry.

PMID- 1974702
TI  - CSF pulsatility in hydrocephalus: respiratory effect on pulse wave slope as an
      indicator of intracranial compliance.
AB  - The effect of inspiration and expiration on the systolic slope of the
      cerebrospinal fluid (CSF) pulse wave has been studied in 83 shunted and non
      shunted patients undergoing diagnostic tests for suspected hydrocephalus. A ratio
      of the systolic CSF pulse slope on inspiration to the same in expiration (I/E
      ratio or index) has proved statistically valid in identifying non-hydrocephalic
      patients from hydrocephalic patients and in separating hydrocephalic patients
      into arrested, communicating and aqueductal stenosis hydrocephalus. The I/E ratio
      depends on the comparative damping effect of intracranial venous venting on the
      systolic CSF pulse slope during inspiration (I) when venous volume is evacuated
      from the cranium by negative mediastinal pressure, and during expiration (E) when
      cranial venous volume flow to heart is minimal due to positive mediastinal
      pressure. The low cranial venous outflow on expiration produces little effect on
      the normal damping of the systolic CSF pulse slope. The high venous outflow on
      inspiration produces a loss of damping, causing a high systolic CSF pulse slope.
      Therefore, exhausted cranial venous volume, or exhausted intracranial compliance,
      produces an I/E ratio approaching 1.0, whereas a normal I/E ratio is between 2.0
      and 3.0. The I/E ratio can presumably be used to assess intracranial compliance
      changes occurring before the dangerous late intracranial pressure (ICP) upward
      surge related to the volume-pressure curve in all clinical problems of increasing
      ICP. The I/E ratio may be used likewise to assess the urgency of treatment for
      any hydrocephalus and increased intracranial pressure problem, i.e. the closer to
      unity the greater the urgency.

PMID- 1974703
TI  - Diagnosis of carotid artery occlusion by duplex scanning.
AB  - This paper reviews 70 patients, with complete occlusion of the internal carotid
      artery, investigated by duplex scanning. The correlation between the echogenicity
      of the occlusion (anechogenic, hypoechogenic or hyperechogenic) and the time
      interval between the ischaemic symptoms and the ultrasonic investigation showed
      that some occlusions are hypoanechogenic and others hyperechogenic, in spite of
      the time interval, and consequently the echogenicity of the occlusion cannot be
      correlated with the time of its formation. Duplex scanning allows a correct
      diagnosis in almost all cases of carotid artery occlusion by comparison of the
      morphological and flowmetric data. The 95% sensitivity in 20 cases was explored
      by digital angiography also. It was concluded that angiography was usually
      unnecessary to confirm a carotid occlusion and its use could be limited to rare,
      doubtful, cases and to patients with contralateral stenosis i.e. candidates for
      surgery.

PMID- 1974704
TI  - Thrombolytic therapy of cerebral arterial occlusion with recombinant tissue
      plasminogen activator.
AB  - This report describes three patients, with acute cerebral arterial occlusion,
      treated with recombinant tissue plasminogen activator (rt-PA). In one patient
      with basilar artery occlusion thrombolytic treatment was initiated 12 h after
      onset of the symptoms. In two patients with angiographically verified occlusion
      of the middle cerebral artery, the treatment was initiated approximately 4.5 h
      after onset of the symptoms. Recombinant tissue plasminogen activator 80-120 mg,
      was infused intra-arterially over 90-100 min via a catheter the tip of which was
      close to the occlusion. This regimen resulted in recanalization in all the
      patients; however, in two patients it was verified by repeat CT scan only. In two
      patients the thrombolytic treatment was successful (the patients improved
      clinically); the third patient died of massive cerebral infarct-related oedema.
      In none of the patients did significant bleeding or other obvious side-effects
      occur. From this preliminary report it is concluded that angiographically proven
      thrombolytic recanalization in acute cerebrovascular occlusion is possible with
      rt-PA. In some patients, however, the treatment is initiated too late. Further
      investigation of the possible indication for thrombolytic therapy in stroke is
      needed.

PMID- 1974705
TI  - Fatal ischaemic brain oedema after unsuccessful thrombolysis.

PMID- 1974706
TI  - Intracerebroventricular infusion but not bolus injection of vasopressin increases
      the cerebrospinal fluid pressure in awake rabbits.
AB  - The effect of intracerebroventricular infusion or injection of arginine
      vasopressin (AVP) was examined in awake rabbits with permanent ventricular
      cannulae. Intracerebroventricular infusion of artificial cerebrospinal fluid
      (CSF) 43 microliters min-1 containing AVP concentrations exceeding 0.4 ng ml-1,
      equivalent to an AVP infusion rate of 17.2 pg min-1, caused a dose-dependent
      increase in intracranial pressure (ICP) of 3 to 5 mmHg after 30-50 min of AVP
      infusion. Intracerebroventricular bolus injection of equivalent doses of AVP did
      not provoke changes in ICP. At the end of the experiments cisternal CSF
      concentrations of AVP were higher after infusion of AVP than after injection of
      the same amount of AVP. The mean arterial blood pressure increased slightly in
      the group of animals infused with AVP at rates above 17.2 pg min-1. It is
      concluded that intracerebroventricular infusion of AVP increases ICP in awake
      rabbits but the mechanism responsible for the elevation of ICP remains
      speculative.

PMID- 1974707
TI  - Compensatory mechanisms in patients with asymptomatic carotid artery occlusion.
AB  - Twelve patients with asymptomatic occlusion of one (n = 8) or both (n = 4)
      internal carotid arteries were examined by positron emission tomography (PET) and
      transcranial Doppler ultrasound. PET measurements included the determination of
      the regional cerebral blood flow (rCBF), oxygen extraction ratio (rOER), cerebral
      metabolic rate of oxygen (rCMRO2), and cerebral metabolic rate of glucose
      consumption (rCMRGlc). Transcranial Doppler ultrasound (TCD) was used to
      determine the pathways and efficacy of collateralization via the circle of Willis
      and included spectrum analysis of flow velocities within the middle and anterior
      cerebral arteries as well as vasoreactivity tests. In correspondence with
      ultrasound evidence of a haemodynamically effective intracranial collateral
      circulation no significant differences between patients and controls were
      observed for rOER, rCMRO2 and rCMRGlc, but rCBF was globally reduced.
      Furthermore, in all patients with unilateral carotid occlusion PET excluded side
      asymmetries of any parameter studied. In contrast, flow velocity parameters
      measured by TCD were significantly reduced ipsilateral and significantly
      increased contralateral to the carotid obstruction. Vasodilative capacities,
      however, remained preserved even in the territory of the occluded carotid system.
      These data indicate that patients with asymptomatic carotid occlusion compensate
      by haemodynamic and not by metabolic mechanisms in contrast to symptomatic
      patients.

PMID- 1974708
TI  - Effect of pulsed electromagnetic fields on calcium tissue changes in focal
      ischaemia.
AB  - The effect of a pulsed electromagnetic field (PEMF) (parameters: 27.1 MHz, 585 W
      peak power, and 65 microseconds pulses, 400 times per second) on rats undergoing
      middle cerebral artery occlusion (MCAo) was investigated. Four groups of eight
      rats each underwent microsurgical MCAo. Two groups were treated with a PEMF
      generator for 2 h following the onset of ischemia and were sacrificed at 4 and 24
      h following the MCAo respectively. The other two groups were also sacrificed at
      the same time intervals. Regional brain sodium, potassium, and calcium tissue
      contents were determined by atomic spectrophotometry. As distinct from results
      found in spinal cord contusion, no significant difference between the PEMF
      treated groups and the non-treatment groups was found. PEMF treatment did not
      alter the 300% rise in calcium tissue dry weight content observed at 24 h
      following MCAo in the infarcted tissue. Regional brain water content was
      determined by the dry weight method. A regionally inconsistent reduction in brain
      water content was noted in the PEMF-treated rats.

PMID- 1974709
TI  - Relationship between chronic raised intracranial pressure and empty sella
      presenting hormonal disturbances.
AB  - The role of intracranial pressure in the development and maintenance of the
      primary empty sella has been pointed out in the literature previously. The
      hormonal changes and clinical features have been evaluated in a 30 year-old
      female patient examined for a convexity meningioma and a 20 year-old patient
      examined for chronic hydrocephalus caused by cured meningitis. Histories and
      investigations revealed an empty sella turcica associated with primary
      amenorrhoea and delayed puberty. The removal of the convexity meningioma resulted
      in loss of amenorrhoea and a rise in plasma gonadotrophins. The establishment of
      a ventriculo-peritoneal shunt did not bring about any changes in hormonal values
      and clinical features except the subjective headache disappeared. The importance
      of consideration of intracranial causes in patients who have delayed puberty or
      absence of menstrual history is briefly emphasized in light of the literature.
      Our data also demonstrated a correlation between an increase in intracranial
      pressure and a deficiency of hormonal secretion by the hypophysis.

PMID- 1974710
TI  - R(-) and S(+) stereoisomers of 11-hydroxy- and 11-methoxy-N-n-propylnoraporphine:
      central dopaminergic behavioral activity in the rat.
AB  - R(-)11-Hydroxy-N-n-propylnoraporphine (11-OH-NPa) induced stereotyped behavior in
      the rat as potently (ED50 = 0.80 mg/kg, i.p.) as R(-)apomorphine (APO) and this
      effect was blocked by haloperidol; the 11-methoxy congener, R(-)11-MeO-NPa, had a
      weak effect (ED50 greater than 10 mg/kg) and the S(+) isomers had none. The
      isomer R(-)11-OH-NPa potentiated locomotion stimulated by apomorphine; S(+)11-OH
      NPa inhibited it and the isomers of 11-MeO-NPa were inactive. Catecholaporphines
      usually are inactive orally, but both R(-) and S(+)11-OH-NPa were similarly
      potent after oral or parenteral administration. The isomer S(+)11-OH-NPa
      inhibited spontaneous and apomorphine-induced locomotion (ID50 = 1.8-2.7 mg/kg,
      p.o. and i.p.) and stereotyped behavior (ID50 = 3 mg/kg, p.o. or i.p.), all
      without inducing catalepsy. While apomorphine was short-acting (1-2 hr), the
      effects of R(-)11-OH-NPa persisted up to 6-7 hr and those of the S(+) isomer for
      at least 2.5 hr; moreover, the efficacy of R(-)11-OH-NPa increased markedly up to
      3-4 hr, although its ED50 was independent of time (ED50 = 1.7-1.9 mg/kg, i.p.
      from 1-3 hr). The total effect of R(-)11-OH-NPa (p.o. or i.p.) over time was more
      than 10-times greater than that of injected apomorphine. These observations
      accord with the reported high (nM) affinity of 11-OH-NPa at cerebral DA receptor
      sites (D2 greater than D1) and weak interactions of the 11-methoxy congener. They
      support the conclusion that the R(-) and S(+) stereoisomers are
      neuropharmacologically active, respectively, as DA agonist and apparent
      antagonist, as was found with the enantiomers of N-n-propylnorapomorphine,
      perhaps due to the low intrinsic postsynaptic agonist activity of the S(+)
      isomers. Moreover, 11-OH-NPa was highly bioavailable orally and unusually long
      acting; it may be absorbed slowly or have active metabolites. Hydroxy
      substitution of aporphines at the 11-position, homologous to the 3-OH of DA,
      evidently is critical for affinity and activity at the DA receptor. These or
      other monohydroxyaporphines may represent leads to potentially useful DA agonist
      or antagonist drugs.

PMID- 1974711
TI  - Spinal dynorphin A (1-17): possible mediator of antianalgesic action.
AB  - Earlier studies from this laboratory indicated that intracerebroventricular
      administration of physostigmine and clonidine activated both a spinal descending
      analgesic and antianalgesic system. It was proposed that the latter was mediated
      spinally by dynorphin A (1-17), because small intrathecal doses (fmol) of
      dynorphin A (1-17) antagonized analgesia, while intrathecal administration of
      naloxone and nor-binaltorphimine (at doses which had no effect on spinal mu and
      kappa receptors) enhanced analgesia by attenuating the antianalgesic component.
      In the present studies in mice, using the tail-flick response, intrathecal
      administration of dynorphin antibody (antiserum to dynorphin) enhanced the
      analgesic effect of (10 min) physostigmine and clonidine given
      intraventricularly. Peak effect for the antiserum was at 1 hr. Inhibition of the
      tail-flick response, induced by DAMGO (Tyr-D-Ala2-Gly-NMePhe4-Gly-ol5, a mu
      agonist), U50, 488 H (trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)
      cyclohexyl]- benzeneacetamide methanesulfonate hydrate, a kappa agonist) and
      morphine was also enhanced by intrathecal administration of dynorphin antiserum.
      Thus, a variety of analgesic agonists appear to activate a dynorphin-mediated
      antianalgesic system. Such a system appears not to be activated by
      intraventricular administration of beta-endorphin and DPDPE (D-Pen2-D-Pen5
      enkephalin, a delta agonist) because neither beta-endorphin- nor DPDPE-induced
      analgesia was enhanced by intrathecal administration of antiserum. The results of
      the experiments with the antibody provide further evidence to support the role of
      dynorphin A (1-17), as a putative endogenous opioid, which mediates an
      antianalgesic descending system in the spinal cord.

PMID- 1974712
TI  - Depletion of catecholamines in the brain of rats differentially affects
      stimulation of locomotor activity by caffeine, D-amphetamine, and
      methylphenidate.
AB  - The purpose of this study was to assess the role of catecholamines in brain, in
      the stimulation of locomotor activity, induced by caffeine, as compared to the
      psychomotor stimulants D-amphetamine and methylphenidate. Adult male rats were
      pretreated with either (1) 2.5 mg/kg (i.p.) reserpine, 24 hr prior to testing of
      locomotor activity, (2) 50 mg/kg (i.p.) alpha-methyl-para-tyrosine (AMPT) 6 hr
      and 2 hr prior to testing of locomotor activity, (3) 200 micrograms/rat (i.c.v.)
      6-hydroxydopamine (6-OHDA), or 25 mg/kg (i.p.) desmethylimipramine (DMI) and 200
      micrograms/rat 6-OHDA (i.c.v.), 6-8 weeks prior to testing. Each treatment group
      had a matched control group. Levels of catecholamines in the forebrain were
      determined in each of the treatment and corresponding control groups. All rats
      were tested with doses of caffeine, D-amphetamine and methylphenidate (excluding
      the 6-OHDA-treated animals), administered in random order intraperitoneally 35
      min before locomotor activity was measured for 30 min. Pretreatment with either
      reserpine or AMPT attenuated the stimulation of locomotor activity induced by
      caffeine and D-amphetamine but not that induced by methylphenidate. The dose
      response curve for amphetamine was shifted downward and to the right by reserpine
      but was flattened by AMPT. The dose-response curve for caffeine was displaced
      downward in a similar manner by both reserpine and AMPT. Treatment with 6-OHDA or
      DMI + 6-OHDA produced the expected changes in the content of catecholamines in
      brain, but failed to modify dose-response curves for caffeine or
      amphetamine.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1974713
TI  - Opposite effects of stimulation of D1 and D2 dopamine receptors on the expression
      of motor seizures in mouse and rat.
AB  - The ability of drugs, selective for dopamine D1 and D2 receptors, to influence
      the production of motor seizures was studied in mice and rats. Mice, which had
      been injected with reserpine (5 mg/kg) to deplete stores of monoamines in brain,
      could be made to convulse 24 hr later by injecting the D1 agonists, SKF 38393 (15
      30 mg/kg) and CY 208-243 (0.3-3 mg/kg). The D2 agonists, lisuride (0.5-5 mg/kg)
      and RU 24213 (0.5-15 mg/kg) and the mixed D1/D2 agonist, apomorphine (0.05-0.5
      mg/kg), had no effect on the seizure thresholds by themselves. However, the
      proconvulsant action of SKF 38393, 15 mg/kg, was prevented by the simultaneous
      injection of lisuride (5 mg/kg), RU 24213 (5 mg/kg) or apomorphine (0.5 mg/kg)
      and also by the selective D1 blocking drug, SCH 23390 (0.1 mg/kg). Rats were made
      to convulse by injecting the cholinergic agonist, pilocarpine (200-600 mg/kg)
      coupled with methyl scopolamine (1 mg/kg), to prevent peripheral autonomic
      effects. The smallest dose of pilocarpine (200 mg/kg) was subconvulsant, whereas
      the larger ones (400 and 600 mg/kg) dose-dependently induced tonic convulsions.
      The drug SKF 38393 (30 mg/kg) was found to be proconvulsant and caused seizures
      to develop in 100% of animals, at all dose levels of pilocarpine. This effect was
      blocked by SCH 23390 (0.25 mg/kg) which, by itself, reduced the severity and
      increased the latency of pilocarpine-induced convulsions, but not their
      frequency. The D2 agonist LY 171555 (0.5 mg/kg) was also anticonvulsant in this
      model and was antagonised by the D2 blocking drug metoclopramide (1.25 mg/kg),
      which was ineffective alone.

PMID- 1974714
TI  - An electrophysiological study of the action of N-methyl-D-aspartate on excitatory
      synaptic transmission in the optic tectum of the frog in vitro.
AB  - Excitatory synaptic field potentials, induced by stimulating optic nerve fibers,
      were recorded from in vitro preparations of the optic tectum of the frog. Bath
      applied N-methyl-D-aspartate (NMDA), glutamate or quisqualate elicited transient
      enhancement in these field potentials, followed by a sustained depression
      reversible on washout. Responses to glutamate or quisqualate and the amplitude of
      control synaptic potentials, were not affected by the NMDA receptor antagonists
      aminophosphonovalerate (APV), 3(2-carboxypiperazin-4-yl)propyl-1-phosphonate
      (CPP), ketamine, magnesium ions or dizocipiline (MK 801) which, on the other
      hand, blocked the effects of NMDA. The antagonist dinitroquinoxaline-2,3-dione
      (DNQX), which is preferential for non-NMDA receptors, blocked the action of
      glutamate and synaptic transmission. In the presence of strychnine, glycine
      reversed the block of NMDA-mediated responses caused by magnesium. It is
      suggested that in the optic tectum of the frog, glutamate is the excitatory
      transmitter of at least one class of optic nerve fibers and that it acts through
      non-NMDA receptors. Although this area of the brain contains a well-developed
      NMDA receptor system, its function in physiological synaptic transmission remains
      to be elucidated.

PMID- 1974715
TI  - Suramin-induced changes in sympathetic neurons: correlation between catecholamine
      fluorescence, tyrosine hydroxylase immunoreactivity and accumulation of pigment
      bodies.
AB  - The effect of suramin, a strong inhibitor of lysosomal enzymes, was studied in
      rat superior cervical (SCG) and dorsal root ganglia (DRG). Ten days after
      administration both types of ganglion showed increased intraneuronal pigment
      fluorescence; in DRG there were also accumulated pigments in Schwann cells.
      Ultrastructurally the pigment bodies were membranous or lamellar inclusion
      bodies. In SCG suramin-induced inclusion bodies were associated with decreased
      catecholamine fluorescence and tyrosine hydroxylase immunoreactivity, suggesting
      that altered activity of lysosomal enzymes and the formation of lysosomal
      inclusion bodies may be coupled with decreased synthesis of neurotransmitters in
      rat sympathetic neurons.

PMID- 1974716
TI  - Beta blocker dose titration in the drug treatment of hypertension.

PMID- 1974717
TI  - Widespread thrombosis and necrotizing arteritis of the liver in a 69-year-old
      woman with symptoms simulating those of temporal arteritis.
AB  - Autopsy findings of widespread thrombosis and necrotizing arteritis of the liver
      in a 69-year-old woman who had clinical symptoms suggesting those of temporal
      (giant cell) arteritis were presented. The lesion of the temporal artery was not
      of temporal arteritis but of thrombosis, part of widespread thrombosis, which
      occurred in the small arteries having hypertensive arteriolopathy. This case also
      had an arteritis of the liver resembling polyarteritis nodosa (PN). The
      pathologic processes demonstrated in this case suggested that the temporal
      arteritis-like symptoms may be brought about by occlusion of the temporal artery.
      Temporal arteritis is a nonfatal and self-limited disease and little information
      has been obtained from autopsy material. Accordingly, it is necessary to collect
      autopsy cases of temporal arteritis to investigate this disease through
      observations of whole bodies. Recently we examined a case which appeared
      clinically having symptoms of temporal arteritis, but the autopsy revealed that
      the symptoms were not brought about by temporal arteritis but by thrombosis of
      the temporal artery. It is the purpose of this paper to present this case and to
      discuss some problems concerning genesis of symptoms of temporal arteritis.

PMID- 1974718
TI  - The epidermal growth factor receptor and the product of the neu protooncogene are
      members of a receptor tyrosine phosphorylation cascade.
AB  - The protein product of the neu protooncogene, p185, is a tyrosine kinase with a
      high degree of sequence homology to the epidermal growth factor (EGF) receptor.
      Although p185 does not bind EGF, EGF stimulates tyrosine phosphorylation of p185.
      To determine the mechanism of this interaction we have used a vaccinia
      virus/bacteriophage T7-based transient gene expression system to induce
      production of normal and kinase-deficient forms of p185 in the absence and
      presence of EGF receptors. Tyrosine phosphorylation of kinase-deficient p185 was
      observed, but only in the presence of the EGF receptor. These findings strongly
      support the hypothesis that p185 is a substrate for the EGF receptor tyrosine
      kinase in a tyrosine kinase cascade.

PMID- 1974719
TI  - Haplotype of multiple polymorphisms resolved by enzymatic amplification of single
      DNA molecules.
AB  - We have developed a reliable method for the direct resolution of haplotypes or
      linkage phase from individuals who are multiply heterozygous in a given genomic
      region. The method is based on single-molecule dilution (SMD) of genomic template
      and amplification via biphasic polymerase chain reaction (booster PCR). We have
      verified the feasibility of the SMD method for a highly polymorphic region within
      the beta-globin cluster by analysis of triply heterozygous individuals of known
      haplotype. This approach should be useful in many studies in population or
      evolutionary genetics and in a variety of clinical settings.

PMID- 1974720
TI  - Molecular mass, biochemical composition, and physicochemical behavior of the
      infectious form of the scrapie precursor protein monomer.
AB  - A highly purified fraction obtained from scrapie (263-K strain)-infected
      hamsters' brains by an alternative procedure without proteinase K treatment
      contained a protease-resistant form of the scrapie precursor protein (PrPSc) and
      infectivity of 9.9 +/- 0.7 log LD50/ml. Polyclonal antibodies produced against
      hamster scrapie amyloid protein (PrP27-30) and used in a neutralization test
      diminished infectivity of the PrPSc preparations by 1.6 log after intracerebral
      inoculation and by 1 log after intraperitoneal inoculation. PrPSc was subjected
      to size-exclusion HPLC; greater than or equal to 60% of the eluted infectious
      units were recovered from the peak with an apparent mass of 30.4 +/- 0.6 kDa.
      Characterization by UV absorption spectra, SDS/PAGE, immunoblots, N-terminal
      amino acid sequence, and neutral sugar and amino sugar analyses demonstrated
      homogeneity of the infectious units. The neutral sugar and amino sugar
      compositional analyses revealed high mannose, glucosamine, fucose, and sialic
      acid content. This demonstrated an extensive posttranslational modification by
      the complex type of N-linked glycosylation and glycane core of C-terminal
      glycolipid of PrPSc. The results correspond to the predicted size, composition,
      and sequence of PrPSc and indicate that this protein may be the only component of
      scrapie infectious unit or the infectious form of scrapie precursor.

PMID- 1974721
TI  - The 60- to 90-kDa parietal cell autoantigen associated with autoimmune gastritis
      is a beta subunit of the gastric H+/K(+)-ATPase (proton pump).
AB  - Autoantibodies in the sera of patients with pernicious anemia recognize, in
      addition to the alpha subunit of the gastric H+/(+)-ATPase, an abundant gastric
      microsomal glycoprotein of apparent Mr 60,000-90,000. Herein we have colocalized
      the glycoprotein and the alpha subunit of the gastric H+/K(+)-ATPase to the
      tubulovesicular membranes of the parietal cell by immunogold electron microscopy.
      Moreover, the glycoprotein and the alpha subunit were coimmunoprecipitated, and
      copurified by immunoaffinity chromatography, with an anti-glycoprotein monoclonal
      antibody. The pig glycoprotein was purified by chromatography on tomato lectin
      Sepharose, and five tryptic peptides from the purified glycoprotein were
      partially sequenced. The complete amino acid sequence, deduced from the
      nucleotide sequence of overlapping cDNA clones, showed 33% similarity to the
      sequence of the beta subunit of the pig kidney Na+/K(+)-ATPase. We therefore
      propose that the 60- to 90-kDa glycoprotein autoantigen is the beta subunit of
      the gastric H+/K(+)-ATPase and that the alpha and beta subunits of the proton
      pump are major targets for autoimmunization in autoimmune gastritis.

PMID- 1974722
TI  - Pharmacologic evidence for nociception resulting from noncontingent "rewarding"
      brain stimulation.
AB  - Prolonged noncontingent electrical stimulation to rewarding brain sites will
      elicit escape behavior in rats. This study was designed to determine if this
      escape behavior is reinforced by the termination of a nociceptive stimulus or
      reinforced by the rewarding effects of the onset of the next stimulus. In the
      present experiment we determined the effects of the hyperalgesic naloxone (NX)
      and the analgesic ethylketocyclazocine (EKC) on the threshold for escape from
      electrical brain stimulation to the medial forebrain bundle-lateral hypothalamic
      area (MFB). Results indicate that EKC (0.5-1.0 mg/kg) raises the escape
      threshold, whereas NX (8.0-16.0 mg/kg) lowers the escape threshold, suggesting
      that escape from electrical brain stimulation to the MFB is the result of the
      nociceptive quality of stimulation and not the result of the rewarding effects of
      the onset of stimulation.

PMID- 1974723
TI  - Degree and extent of response to sulphasalazine or penicillamine therapy for
      rheumatoid arthritis: results from a routine clinical environment over a two-year
      period.
AB  - An attempt was made to audit the clinical usefulness of sulphasalazine and
      penicillamine in patients with rheumatoid arthritis (RA) managed in a routine out
      patient setting with assistance from general practitioners and to ascertain
      whether clinically significant differences can be shown between these two 'second
      line' agents. The degree and extent of change in, and the usefulness of, various
      parameters of disease activity were also evaluated. Two hundred patients with
      active rheumatoid arthritis were randomly allocated to either sulphasalazine or
      penicillamine and monitored for a minimum of two years. Fifty-one percent of the
      102 patients who received sulphasalazine continued treatment for two years,
      compared with 40 per cent of the 98 patients allocated to penicillamine. The
      proportion of patients stopping therapy because of adverse reactions or due to
      lack or loss of effect was similar in the two groups. There was no difference
      between the two groups in the extent of improvement in clinical and laboratory
      variables at one and two years. The majority of patients showed improvement in
      most measured parameters; very few showed global improvement. The degree of
      improvement varied with the parameter assessed, being greatest in relatively
      easily measured variables such as duration of morning stiffness and ESR, and
      least for functional index. The effect and toxicity of these two agents in this
      setting was as anticipated. No clinically relevant difference could be
      demonstrated between the two drugs.

PMID- 1974724
TI  - The National Cancer Institute phase I study of 2',3'-dideoxyinosine
      administration in adults with AIDS or AIDS-related complex: analysis of activity
      and toxicity profiles.
AB  - 2',3'-Dideoxyinosine (didanosine; ddI) was administered to 37 adults with AIDS or
      AIDS-related complex in an escalating-dose phase I study. Groups of three or four
      patients received intravenous dosages of 0.4 mg/(kg.d) to 25.6 mg/(kg.d) divided
      into two or three daily doses for 2 weeks, followed by oral ddI at twice the
      intravenous dosages. When given with antacids, ddI was well absorbed by the oral
      route and penetrated into the cerebrospinal fluid. The patients had an increase
      in mean number of CD4+ cells from 114/mm3 at entry to 161/mm3 at week 6 (P =
      .00004). They also had an increase in the CD4+/CD8+ ratio and in total number of
      lymphocytes. Sixteen of 18 evaluable patients had a decrease in levels of human
      immunodeficiency virus p24 antigen by week 6 (P = .0034). Many patients reported
      increased energy and appetite and gained weight. Dose-limiting toxicities at high
      dosages were painful peripheral neuropathy and sporadic pancreatitis. However,
      dosages up to 9.6 mg/(kg.d) have been tolerated in patients for 11-14 months.
      Thus, ddI has activity against human immunodeficiency virus at dosages that can
      be tolerated for approximately 1 year. However, life-threatening pancreatitis is
      a possible complication even at low dosages, and the best ways to manage and
      avoid adverse effects are still under study.

PMID- 1974725
TI  - Phase I study of 2',3'-dideoxyinosine: experience with 19 patients at New York
      University Medical Center.
AB  - We performed a phase I study of escalating dosages of 2',3'-dideoxyinosine
      (didanosine; ddI) in 19 patients with AIDS or AIDS-related complex in order (1)
      to establish the maximal tolerated dosage, (2) to determine the nature of toxic
      adverse effects, (3) to measure changes in levels of circulating human
      immunodeficiency virus p24 antigen and in CD4+ cell counts, and (4) to evaluate
      the pharmacokinetics of ddI. Almost all patients had received zidovudine therapy
      previously. The maximal tolerated dosage of ddI was found to be approximately 12
      mg/(kg.d) when it was administered orally for 28 weeks. The major dosage-limiting
      adverse effects encountered were neuropathy, pancreatitis, and hepatitis. These
      occurred at dosages higher than those associated with decreases in levels of p24
      antigen. The major toxic effects of ddI are different from those associated with
      zidovudine. At the proper dosage, ddI may prove to be an effective agent for the
      chronic treatment of infection with human immunodeficiency virus and should be
      especially useful in the treatment of patients who cannot tolerate zidovudine.

PMID- 1974726
TI  - 2',3'-Dideoxyinosine in patients with AIDS or AIDS-related complex.
AB  - Twenty-one patients with AIDS or AIDS-related complex (ARC) received 2',3'
      dideoxyinosine (didanosine; ddI) intravenously and then orally (initial dosages
      of 0.4 mg/kg and 0.8 mg/kg every 12 hours, respectively) for 6-44 weeks in an
      escalating-dose study. The major dose-limiting effects were peripheral neuropathy
      (three patients) and pancreatitis (two patients), which were observed at dosages
      greater than or equal to 20 mg/(kg.d). Hyperuricemia occurred at greater than or
      equal to 30 mg/(kg.d). No hematologic toxicity developed except for possible
      sporadic thrombocytopenia (two patients). Significant decreases in serum levels
      of p24 antigen and increases in CD4+ and CD8+ lymphocytes were noted at 2, 6, and
      10-20 weeks and over a wide range of dosages, including the lowest given. Most
      patients had an increased feeling of well-being and/or a weight gain of greater
      than or equal to 2 kg at 6 weeks. For this population, ddI has promise as a
      therapeutic agent, thus warranting further study of this agent in controlled
      clinical trials.

PMID- 1974727
TI  - Treatment of AIDS and AIDS-related complex with 2',3'-dideoxyinosine given once
      daily.
AB  - In a phase I dosage-finding trial, 2',3'-dideoxyinosine (didanosine; ddI) was
      administered once daily to 36 patients with AIDS or AIDS-related complex for up
      to 65 weeks (mean, 32.1 weeks) at six dosage levels. Thirteen of 18 patients
      previously treated with zidovudine had developed hematologic intolerance. The
      maximal tolerated dosage of ddI was 12 mg/(kg.d); dose-limiting toxicities were
      pancreatitis and peripheral neuropathy. Other toxicities included elevation in
      hepatic transaminase levels, rash, cardiac conduction abnormality, and
      asymptomatic hyperuricemia. Eighty-six percent of patients who completed 6 weeks
      of treatment showed improvement in constitutional symptoms and significant weight
      gain. In patients treated with ddI, the mean number of CD4+ lymphocytes increased
      from 124/mm3 at baseline to 199/mm3 at 24 weeks (P = .0027) and the mean
      leukocyte count, total lymphocyte count, and hemoglobin level showed increases
      (all P less than .01) after 12 weeks. Serum levels of viral p24 antigen decreased
      greater than or equal to 50% in 14 of 19 assessable patients. No differences
      between the responses of patients previously treated with zidovudine and those of
      zidovudine-naive patients were observed. These results indicate that ddI has
      significant antiretroviral activity in vivo and a toxicity profile different from
      that of zidovudine.

PMID- 1974729
TI  - [The role of invasive procedures in the diagnosis of heart failure].
AB  - Definition, pathophysiologic aspects and the dynamic of heart failure as well as
      the increasing of incidence and mortality have been discussed. The main
      determinants of cardiac function like contractility, preload, afterload,
      ventricular wall kinetic and neurohumoral factors have been analyzed. It has been
      shown, that the parameters of contractility in auxotonic phase have more
      practical significance than parameters of isovolumic phase of contraction. The
      actual importance of the invasive methods for assessment of pressure and volume
      parameters in regard to non-invasive techniques has been demonstrated. Depending
      on the changing of left ventricular filling pressure and cardiac output at rest
      and during exercise different stages of cardiac failure can be recognized. The
      importance of hemodynamic monitoring for evaluation of different therapeutic
      interventions especially in acute cardiac failure has been emphasized.

PMID- 1974728
TI  - Effect of ciprofibrate, bezafibrate, and LY171883 on peroxisomal beta-oxidation
      in cultured rat, dog, and rhesus monkey hepatocytes.
AB  - Cultured rat hepatocytes have been used extensively to study the mechanisms of
      chemically induced peroxisome proliferation. Hepatocytes from nonrodent species
      have been used on a limited scale to study interspecies differences in the
      response. Because of their importance in pharmaceutical safety assessment, we
      have developed a model to study the response of beagle dog and rhesus monkey
      hepatocytes to peroxisome proliferators. Treatment of the hepatocytes with
      peroxisome proliferators was begun after 20 hr in culture and continued for 72
      hr. Untreated rat, dog, and monkey hepatocytes retained 62, 42, and 43% of their
      initial (20 hr) peroxisomal beta-oxidation activity throughout 92 hr of culture.
      Ciprofibrate, bezafibrate, and LY171883 caused a dose-related increase in beta
      oxidation in rat hepatocytes to a maximum of 10-, 8-, and 5-fold, respectively.
      In dog and monkey hepatocytes the increases in beta-oxidation were less than 2
      fold. Peroxisome morphology in dog and monkey hepatocytes appeared to be
      unchanged by the drugs. Morphometric analysis in monkey hepatocytes showed no
      increase in peroxisome volume fraction in response to the chemicals. Treatment of
      dog and monkey hepatocytes with dexamethasone and glucagon during the final 24 hr
      in culture caused a 4- to 6-fold increase in tyrosine aminotransferase activity.
      This induction is characteristic of the in vivo response. The small increase in
      beta-oxidation reflects the relative insensitivity of the dog and monkey liver to
      peroxisome proliferators in vivo rather than a loss of sensitivity during
      culture. Cultured hepatocytes from beagle dog and rhesus monkey may provide a
      model for studying the mechanisms underlying the interspecies differences. Such
      information would help clarify the relevance of rodent data in human risk
      assessment.

PMID- 1974730
TI  - [The adhesins of enterotoxigenic Escherichia coli: their role in the pathogenesis
      of diarrhea and their genetic control].

PMID- 1974731
TI  - [The clinical course of allergic diseases in children and the T-lymphocyte
      dynamics with adsorbed DT-m vaccination against a background of drug therapy].
AB  - In case of immunization with adsorbed diphtheria-tetanus toxoid with reduced
      antigen content the treatment of children with calcium pantothenate in
      combination with chloropyramine proved to be most effective. This was confirmed
      by the absence of postvaccinal complications and by the most active restoration
      of the pool of active T cells as early as 2 months after immunization. After the
      preliminary treatment of children with allergic diseases with calcium
      pantothenate, glyceram, chloropyramine or their combinations the number of T
      lymphocytes decreased differently in children receiving different medicinal
      preparations. In 2 months after immunization the restoration of the pool of T
      cells was incomplete in children with allergic diseases and considerably more
      intensive in healthy children.

PMID- 1974732
TI  - Cholinergic and noradrenergic nervous systems in the cynomolgus monkey cochlea.
AB  - The cholinergic and noradrenergic nervous systems in the cochleas of cynomolgus
      monkeys were examined by histochemical and immunohistochemical demonstration of
      acetylcholinesterase (AChE) and tyrosine hydroxylase (TH) and/or dopamine B
      hydroxylase (DBH), respectively. AChE activity was demonstrated in the efferent
      fibers making synaptic contact with the perikarya and the cell processes of type
      II neurons. Type II neurons also demonstrated AChE activity on the cell surface
      and their neurites, suggesting that the AChE-positive fibers in the simian
      cochlear nerve trunk, previously believed to be of efferent origin, are the
      central processes of type II neurons. TH-like and DBH-like immunoreactivity of
      beaded unmyelinated fibers demonstrated similar distribution throughout the
      cochlear nerve trunk, Rosenthal's canal, and osseous spiral lamina. During their
      course, they came in contact with unmyelinated efferent fibers and neurites of
      type II neurons and abutted blood vessels. However, their distribution was not
      restricted to following blood vessels or cochlear nerve fibers. These
      observations indicate that the sympathetic nerve supply and olivocochlear
      efferent system in the cochleas of monkeys differ from those of smaller animals.

PMID- 1974734
TI  - Islet cell tumors in von Hippel-Lindau disease: increased prevalence and
      relationship to the multiple endocrine neoplasias.
AB  - Von Hippel-Lindau disease is a rare, autosomal-dominant disorder characterized by
      CNS hemangioblastomas, retinal angiomas, renal cell carcinomas,
      pheochromocytomas, and visceral cysts. The occurrence of islet cell tumors in von
      Hippel-Lindau disease has been noted recently. Because of the coexistence of both
      islet cell tumors and pheochromocytomas in some patients with this disorder, it
      has been proposed that there may be a continuum of the multiple endocrine
      neoplasias. However, no large, multifamily study has been published evaluating
      the prevalence of islet cell tumors and pheochromocytomas in von Hippel-Lindau
      disease. To assess the frequency of islet cell tumors in this disorder and its
      relationship to the multiple endocrine neoplasias, we reviewed the clinical and
      imaging findings of all patients with von Hippel-Lindau disease evaluated at the
      Mayo Clinic between January 1979 and December 1989. Forty-three patients with von
      Hippel-Lindau disease from over 25 kindreds were found. Cross-sectional imaging
      of the pancreas had been performed in 35. Islet cell tumors were found in six
      (17%) of these, three islet cell adenomas and three islet cell carcinomas. No
      patient presented with endocrine-related symptoms; four tumors were detected
      during screening examinations of the abdomen. Two (33%) of these six patients had
      a coexisting pheochromocytoma. Our review of a large number of patients from many
      different families with von Hippel-Lindau disease revealed a high prevalence of
      islet cell tumors and the frequent coexistence of islet cell tumors and
      pheochromocytomas. This latter finding supports a continuum of the multiple
      endocrine neoplastic syndromes.

PMID- 1974733
TI  - Antiinflammatory effects of various drugs on acetic acid induced colitis in the
      rat.
AB  - The efficacy of various drugs used to treat ulcerative colitis, (sulfasalazine, 5
      aminosalicylate, hydrocortisone) was investigated in a model of acetic acid
      induced colitis in the rat. Subsequently, we tested the ability of antioxidant/5
      lipoxygenase inhibitors (gossypol and nordihydroguiaretic acid [NDGA]) and a
      cyclooxygenase inhibitor (indomethacin) to attenuate the macroscopic colonic
      damage and/or neutrophil influx (myeloperoxidase activity [MPO]) associated with
      this model of colitis. Oral pretreatment with either sulfasalazine, gossypol, or
      NDGA significantly decreased colonic MPO activity induced by acetic acid.
      Intrarectal administration of such drugs resulted in an even larger reduction of
      the colonic inflammation, with gossypol being the most potent compound. Oral or
      intrarectal administration of corticosteroids (dexamethasone, hydrocortisone)
      also attenuated the parameters of acetic acid induced colitis. In contrast,
      pretreatment with indomethacin was ineffective, or when administered daily after
      colitis induction, indomethacin actually increased colonic neutrophil influx
      significantly. Our data suggest that both the route of drug administration and
      dosing regimen employed affect the antiinflammatory potency and/or efficacy of
      compounds on colitis induced by acetic acid in the rat. Drugs which were
      effective against this colitis may act by scavenging of oxygen derived free
      radicals.

PMID- 1974735
TI  - Infarcted undescended testis appearing as a calcified abdominal mass in an adult.

PMID- 1974736
TI  - Differential diagnosis between complete mole and hydropic abortus by
      deoxyribonucleic acid fingerprints.
AB  - We used a new method of deoxyribonucleic acid fingerprint analysis to obtain the
      differential diagnosis between complete mole and hydropic abortus. This method
      with a deoxyribonucleic acid minisatellite probe requires only a small amount of
      tissue sample and peripheral blood, and presents individual specific restriction
      fragment length polymorphisms (deoxyribonucleic acid "fingerprints") by
      simultaneous detection of many hypervariable regions (minisatellite regions)
      widely dispersed in the human genome. Southern blot hybridization showed that in
      cases of complete mole, all polymorphic fragments were exclusively inherited from
      the father. Some of the polymorphic bands of paternal deoxyribonucleic acid were
      not observed in molar deoxyribonucleic acid. However, in the hydropic abortus,
      the polymorphic fragments could be traced back to its parent. These results
      indicate that deoxyribonucleic acid fingerprints could distinguish the abnormal
      fertilization of complete mole (androgenesis) from the normal fertilization of
      hydropic abortus by identifying the difference in genetic variations between
      complete mole and hydropic abortus at the deoxyribonucleic acid level.

PMID- 1974737
TI  - Dopamine inhibits Na(+)-H+ exchanger activity in renal BBMV by stimulation of
      adenylate cyclase.
AB  - To determine a renal tubular mechanism for the natriuretic effect of dopamine
      (DA) and DA-1 agonists, we measured Na(+)-H+ exchange activity (amiloride
      sensitive) in rat renal cortical brush-border membrane vesicles (BBMV). Renal
      cortical tissues were preincubated with ligands before BBMV preparation to study
      Na(+)-H+ exchange activity in the absence of the added ligands that may compete
      for ion binding sites of the exchanger. DA and DA-1 agonist-inhibited Na(+)-H+
      exchange activity was concentration and time dependent. The inhibitory effect was
      not due to increased permeability, collapse of the proton gradient, or change in
      vesicle size and did not extend to Na(+)-glucose symport. DA-2 agonists had no
      effect, whereas alpha-adrenergic agonists increased Na(+)-H+ exchange activity.
      Kinetic analysis revealed that the DA-1 agonist inhibited Na(+)-H+ exchange
      activity by a noncompetitive process. 2',5'-Dideoxyadenosine inhibited adenylate
      cyclase activity and reversed the inhibitory effect of DA-1 agonist on the
      exchanger. H4, an isoquinoline sulfonamide, which inhibits protein kinase A, also
      reversed the inhibitory effect of DA-1 agonist on the exchanger. Thus the DA-1
      agonist-mediated inhibition of Na(+)-H+ exchange activity in BBMV is a receptor
      mediated adenylate cyclase-linked process.

PMID- 1974738
TI  - Preferential proximal coronary dilation by activators of guanylate cyclase in
      awake dogs.
AB  - The vasodilation effects of activators of guanylate cyclase, atrial natriuretic
      peptide (ANP), nitroglycerin (NTG), and acetylcholine (ACh), on the epicardial
      conductance arteries and the distal resistance coronary vessels were examined in
      chronically instrumented awake dogs and related serially to plasma guanosine
      3',5'-cyclic monophosphate (cGMP) levels. Left atrial bolus injections of ANP (3
      micrograms/kg; n = 7), NTG (13 micrograms/kg; n = 7), or ACh (0.13 micrograms/kg;
      n = 3) induced sustained increases in epicardial coronary dimension (ultrasonic
      crystals), 3.3, 5.7, and 6.7%, respectively, lasting greater than 40 min for ANP
      and NTG and greater than 3 min for ACh, and relatively brief increases in blood
      flow (resistance artery vasomotion) for each agent. Plasma samples withdrawn
      serially after injections of each agent demonstrated that only ANP increased cGMP
      level; the time course of ANP-induced epicardial vasodilation followed more
      closely the increase in cGMP than that of plasma ANP. These data demonstrated
      that these three activators of guanylate cyclase induced preferential sustained
      epicardial vasodilation and only brief distal coronary vasodilation with minor or
      no change in systemic hemodynamics. The prolonged increase in plasma cGMP after
      ANP injection suggested continuous cGMP production during ANP-induced proximal
      vasodilation. These data demonstrate a striking heterogeneity of vasomotor
      responses in the coronary arterial vasculature and suggest that cGMP-mediated
      vasodilation mechanisms are more predominant in proximal conductance arteries
      compared with distal resistance vessels.

PMID- 1974739
TI  - Angiotensin II and alpha-agonist. I. Responses of ovine fetoplacental
      vasculature.
AB  - During ovine pregnancy the uteroplacental vasculature is less responsive to
      angiotensin II (ANG II)-induced vasoconstriction than the systemic vasculature,
      whereas responses to alpha-agonists are just the opposite. Comparisons of fetal
      systemic and placental vascular responses to these agents are not well described,
      nor have they been compared with maternal responses. We determined steady-state
      responses to fetal infusions (5-7 min) of ANG II (0.023-5.73 micrograms/min) and
      phenylephrine (PHEN, 0.031-7.64 micrograms/min), continuously monitoring mean
      arterial pressure (MAP), heart rate (HR), and umbilical blood flow (UmBF).
      Although both vasoconstrictors caused dose-dependent increases in MAP and
      umbilical vascular resistance (UmVR), responsiveness (delta MAP and delta UmVR)
      to ANG II (mol/min) was 35- to 60-fold greater than to PHEN. ANG II caused dose
      dependent decreases in UmBF (2-48%); PHEN had minimal effects except at the
      highest dose, UmBF decreasing only 18%. Although patterns of fetal responses of
      MAP, UmBF, and UmVR to ANG II resembled maternal responses of MAP and uterine
      blood flow and uterine vascular resistance, the former were greatly attenuated.
      Similar observations were made with PHEN for UmBF and UmVR but not MAP. ANG II is
      a more potent fetal systemic and placental vasoconstrictor than PHEN; however,
      compared with those of the mother the responses are attenuated. Moreover, the
      fetoplacental vascular bed appears unresponsive to alpha-adrenergic stimulation,
      possibly reflecting a mechanism for maintaining UmBF when plasma catecholamines
      are elevated.

PMID- 1974740
TI  - Angiotensin II and alpha-agonist. II. Effects on ovine fetoplacental
      prostaglandins.
AB  - The fetoplacental vasculature is more sensitive to angiotensin II (ANG II) than
      to alpha-agonists, possibly reflecting their differing effects on vascular
      prostaglandin (PG) production. To examine this we studied in fetal sheep (123-138
      days) the effects of ANG II (n = 7; 0.057, 1.15, and 5.73 micrograms/min) and
      phenylephrine (PHEN, n = 7; 0.306, 1.53, and 7.64 micrograms/min) on mean
      arterial pressure (MAP), heart rate (HR), and simultaneous measurements of
      umbilical arterial and venous PGE2, 6-keto-PGF1 alpha (PGI2) and thromboxane B2
      (TxB2) concentrations. ANG II increased MAP and decreased HR dose dependently (P
      less than 0.05). Basal umbilical venous plasma PGE2 levels exceeded PGI2 (P less
      than 0.001) and increased during ANG II infusions from 502 +/- 63 to 516 +/- 113,
      647 +/- 188, and 1,968 +/- 541 pg/ml (mean +/- SE, P less than 0.05), as did
      venous-arterial concentration differences (129 +/- 26 to 179 +/- 47, 244 +/- 58,
      and 1,287 +/- 507 pg/ml, respectively; P less than 0.05). ANG II also increased
      umbilical venous PGI2 levels from 110 +/- 13 to 116 +/- 24, 144 +/- 46, and 680
      +/- 147 pg/ml (P less than 0.01) and the venous-arterial concentration difference
      from 3 +/- 6 to 20 +/- 16, 41 +/- 27, and 405 +/- 122 pg/ml (P less than 0.05),
      respectively. ANG II had no effect on plasma TxB2, and no umbilical venous
      arterial concentration differences existed. Although PHEN increased MAP and
      decreased HR, plasma eicosanoid concentrations were unaltered. The fetus is more
      sensitive to ANG II than PHEN; however, only ANG II increased placental PGE2 and
      PGI2 production.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1974741
TI  - Arteriolar reactivity in vivo is influenced by an intramural diffusion barrier.
AB  - The endothelium of the hamster cheek pouch arteriole in vitro is able to greatly
      reduce the potency of luminally applied water-soluble drugs by acting as a
      barrier to diffusion from the lumen to the smooth muscle [Lew, Rivers, and
      Duling. Am. J. Physiol. 257 (Heart Circ. Physiol. 26): H10-H16, 1989]. Lipid
      soluble drugs appear unaffected by the diffusion barrier, presumably because
      their ability to cross cell membranes allows them to freely cross the
      endothelium. We compared the effects of two alpha 1-adrenoceptor agonists,
      phenylephrine (water soluble) and SKF 89748A (lipid soluble), on systemic blood
      pressure and the arterioles of the hamster cheek pouch in vivo. Both agonists
      were able to activate the arterioles when applied topically to the outside of the
      arterioles (extraluminal application). The agonists were also injected as a brief
      bolus into the aortic arch at doses chosen to elicit similar peak pressor
      responses. At all levels of pressor response, the arteriolar responses to
      phenylephrine were smaller than those to SKF 89748A. In the cremasteric
      vasculature SKF 89748A was similarly found to be more effective in activating the
      arterioles after intravascular administration than was phenylephrine. We conclude
      that an intramural diffusion barrier exists in the arteriolar wall in vivo and
      that it can influence vascular reactivity.

PMID- 1974742
TI  - Metabolic characteristics of cat kidney: failure to adapt to metabolic acidosis.
AB  - During studies performed on domestic cats made acidotic with ammonium chloride,
      it was found that the cat kidney is unable to adapt to metabolic acidosis. Renal
      proximal tubules do not increase their production of ammonia or glucose from
      glutamine during acidosis. During in vivo studies, the renal excretion of ammonia
      did not change much during acidosis. Other metabolic parameters in the cat were
      not very different from those found in other animals such as rat or dog. However,
      it was found that cats may show a relatively high plasma glucose concentration
      compared with other animals. Plasma insulin concentration was normal, and the
      animals showed no evidence of diabetes mellitus. It is not known whether
      limitation of ammoniagenesis and elevated plasma glucose concentration also
      characterize larger felidae such as panthers and cougars.

PMID- 1974743
TI  - Continuous versus targeted medication in schizophrenic outpatients: outcome
      results.
AB  - The authors report on the outcome of treatment of 116 outpatients with chronic
      schizophrenia who were assigned to a 2-year, single-blind course of treatment
      with either targeted or continuous medication. These patients were not restricted
      to those who were good candidates for a medication reduction strategy. Continuous
      medication was superior to targeted medication in preventing decompensations and
      hospitalizations and in extent of employment at 2 years. Other measures of
      psychopathology and functioning at 1 and 2 years did not differentiate the two
      groups of patients. The targeted approach achieved a substantial reduction in
      total medication through a reduction in the number of days of medication
      administration.

PMID- 1974744
TI  - Neuroleptic malignant syndrome in 12 of 9,792 Chinese inpatients exposed to
      neuroleptics: a prospective study.
AB  - In a prospective study of an estimated 9,792 inpatients treated with neuroleptic
      medication at a large Chinese psychiatric hospital, 12 patients developed
      neuroleptic malignant syndrome. The estimated prevalence of neuroleptic malignant
      syndrome in these psychiatric inpatients was 1.23/1,000 (95% confidence interval
      = 0.63/1,000 to 2.14/1,000). Unlike other investigators, the authors found that
      young adulthood, nonschizophrenic illness, oral high-potency neuroleptics, and
      concurrent use of lithium were not important risk factors for neuroleptic
      malignant syndrome. However, depot fluphenazine decanoate, particularly if used
      without an antiparkinsonian agent, was a risk factor.

PMID- 1974745
TI  - Factors in the development of severe forms of tardive dyskinesia.
AB  - The authors evaluated 558 patients for tardive dyskinesia. They found that the
      prevalence of tardive dyskinesia was 34%. There were no differences between men
      and women in prevalence of tardive dyskinesia. However, severe tardive dyskinesia
      was found to occur more in male patients 40 years old or younger and in female
      patients 71 years old or older. Patients with mild tardive dyskinesia received
      more neuroleptics than did patients with moderate and severe forms. However,
      patients with moderate tardive dyskinesia had significantly more drug-free
      periods in their drug histories than did patients with mild tardive dyskinesia.

PMID- 1974746
TI  - Life events and the course of bipolar disorder.
AB  - The authors examined the impact of life stress on the course of bipolar disorder
      over a 2-year period in a group of 61 outpatients. The patients were followed
      prospectively with ongoing assessments of stressful life events, symptoms, levels
      of maintenance medication, and compliance with treatment regimens. As predicted,
      survival analyses indicated a significant association between life events and
      relapse or recurrence of the disorder. These effects could not be explained by
      differences in levels of medication or compliance. Further research is
      recommended to examine which specific subgroups of bipolar patients are most
      susceptible to stress.

PMID- 1974747
TI  - Prevalence of neuroleptic-induced dystonia in mania and schizophrenia.
AB  - In a prospective study of 41 acutely psychotic patients, neuroleptic-induced
      dystonic reactions occurred in 62.5% of the manic patients (10 of 16) and 66.7%
      of the schizophrenic patients (10 of 15), a nonsignificant difference. These
      findings contradict a recent report suggesting a higher risk for this side effect
      in mania.

PMID- 1974748
TI  - [Preoperative treatment with beta-receptor blockers and isoflurane anesthesia.
      Hemodynamic interactions in patients with coronary disease].
AB  - Although many patients undergoing general anesthesia and surgery are pretreated
      with beta-adrenoceptor blocking drugs, hemodynamic interactions of beta-blockers
      and volatile anesthetics have so far only been studied in animals. We therefore
      designed a clinical study to evaluate the relationship between the extent of
      preoperative beta-adrenoceptor blockade and the hemodynamic effects of isoflurane
      anesthesia. Sixty-one patients with coronary artery disease (CAD) and normal
      global left ventricular function scheduled for elective myocardial
      revascularization were studied immediately prior to surgery. One group of
      patients (n = 39) had been treated with beta-adrenoceptor blocking agents for at
      least 3 weeks up to and including the day of surgery. The degree of clinical beta
      adrenoceptor blockade was quantified using the isoproterenol sensitivity test.
      The dose of isoproterenol required to increase heart rate by 25 beats/min was
      defined as the chronotropic dose 25 (CD25), representing the degree of beta
      adrenoceptor blockade. Hemodynamic data were collected before and during
      isoflurane anesthesia (0.5%-0.6% end-tidal) plus 50% nitrous oxide. Twenty-two
      patients without preoperative beta-blocker therapy served as a control group.
      Preanesthetic values of cardiac index (CI), heart rate (HR) and mean arterial
      pressure (MAP) were lower in patients pretreated with beta-blocking drugs, but
      statistically these differences were not significant when compared to data
      obtained in unblocked patients. Isoflurane anesthesia caused significant
      reductions of CI and arterial blood pressure. However, there were no significant
      differences in the absolute values or the percentage changes compared to baseline
      data obtained in awake patients between the two groups.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1974749
TI  - Restriction fragment length polymorphism analysis of the kappa-casein locus in
      cattle.
AB  - The two common genetic variants (A and B) of bovine kappa-casein originate from
      two point mutations in the codons for the aminoacids in position 136 and 148.
      These mutations give rise to polymorphic sites for the restriction endonucleases
      Hin dIII, AluI, HinfI, Mbo II and TaqI. We have examined DNAs of several Italian
      Friesian cows and bulls of known and unknown genotype by Southern analyses using
      kappa-casein cDNA probes. Restriction fragment length polymorphisms (RFLPs)
      specific for the A and B alleles were identified for each of the above enzymes,
      except for AluI, which has a non-polymorphic site 12bp away from the polymorphic
      one. We have also found two new polymorphic sites for MboII and TaqI in the non
      coding regions. These sites differentiate the A allele into two new variants,
      named A1 and A2. The RFLP analysis permits the characterization of kappa-casein
      alleles even in the absence of their expression. This should facilitate selective
      breeding programmes aimed at increasing the frequency of the kappa-casein B
      allele whose product improves the cheesemaking properties of milk.

PMID- 1974750
TI  - Studies on the bovine major histocompatibility class I and class II antigens
      using homozygous typing cells and antigen-specific BoT4+ blast cells.
AB  - Animals were identified from two sire lines as being homozygous for the class I
      bovine lymphocyte antigen (BoLA-A) w23. These animals were also shown to be
      homozygous for class II antigens (BoLA-D) which, however, differed between the
      two sire lines. Lymphocytes from these animals were then used either as
      stimulator cells in one-way mixed lymphocyte reactions (MLR) with all animals in
      the herd carrying the w23 antigen or as antigen presenting cells to bovine T4+
      cell blasts. It was shown that, within each sire line, the genes encoding the MHC
      class I and class II antigens were closely linked. There were no detected
      recombinations between the MHC class I and class II regions nor within the BoLA-D
      region responsible for mixed lymphocyte reactivity. MLR typing of MHC class II
      antigens correlated with the results from T-lymphocyte proliferation studies.
      Cells from these cattle, which are homozygous at the class I and II MHC loci but
      differ in the class II antigen expressed, could be used to type the BoLA-D of
      other cattle.

PMID- 1974751
TI  - Detection of bovine kappa-casein genomic variants by the polymerase chain
      reaction method.

PMID- 1974752
TI  - Increasing viral burden in CD4+ T cells from patients with human immunodeficiency
      virus (HIV) infection reflects rapidly progressive immunosuppression and clinical
      disease.
AB  - OBJECTIVE: To determine over time the relation between viral burden and
      immunologic decline in patients with asymptomatic human immunodeficiency virus
      (HIV) infection. DESIGN: Blind analysis of cell samples from matched cohorts for
      HIV proviral DNA by polymerase chain reaction, retrospective analysis of clinical
      data on patients, and prospective follow-up of patients seropositive for the
      human immunodeficiency virus type 1 (HIV-1). SETTING: National research clinic
      and academic medical centers. PATIENTS: Cohort 1 included 12 healthy HIV-1
      seropositive patients (average follow-up, 14 months): Six patients had stable
      disease and 6 developed rapidly progressive disease. Cohort 2 included 15 healthy
      HIV-1-seropositive patients from the Multi-center AIDS Cohort Study (average
      follow-up, 32 months): Eight patients had stable disease and 7 developed rapidly
      progressive disease. LABORATORY STUDIES: Quantitative polymerase chain reaction
      was done to determine the HIV-1 viral burden in sort-purified CD4+ T cells
      obtained from patients at various timepoints. MEASUREMENTS AND MAIN RESULTS: In
      patients who remained asymptomatic, frequencies of HIV-infected CD4+ T cells were
      low (less than 1/10,000 to 1/1000) at study entry and increased only minimally
      (none higher than 1/1000). In contrast, among patients who developed HIV-related
      symptoms including the acquired immunodeficiency syndrome (AIDS) despite having
      similar CD4 counts, frequencies of HIV-infected CD4+ T cells were higher at entry
      (greater than 1/1000) and increased substantially (greater than 1/100) in most
      within 3 months of developing progressive disease. This increase in HIV burden
      coincided with a significant decline over time in the percent of T4 cells (31% to
      16%), whereas the percent of T4 cells was unchanged in persons who remained
      asymptomatic (33% to 34%). CONCLUSIONS: Increasing viral burden in peripheral
      blood CD4+ T-cells is directly associated with a progressive decline in CD4+ T
      cells and deteriorating clinical course in HIV-infected patients.

PMID- 1974753
TI  - Involvement of the brain noradrenaline system in emotional changes caused by
      stress in rats.

PMID- 1974754
TI  - Studies of regulation of gastrin synthesis and post-translational processing by
      molecular biology approaches.
AB  - We have examined the regulation of gene expression and post-translational
      processing of progastrin by starvation and feeding in rats. An oligonucleotide
      complementary to rat preprogastrin cDNA was used in RNA blot and hybridization
      analysis to measure gastrin mRNA levels. A region-specific antibody raised
      against the predicted amino acid sequence of the carboxyl terminal extension of
      progastrin was used for quantitation of progastrin peptides. The effects of
      starvation and of refeeding on rat antral gastrin mRNA and pro-hormone peptide
      levels were examined in rats starved for 48 h and after refeeding with a solid
      meal. Antral gastrin mRNA concentrations decreased to a plateau level (30% of the
      nonstarved control) after 48 h of starvation. Immunoreactive gastrin
      concentration decreased threefold, but progastrin processing intermediates did
      not decrease significantly during fasting. Following refeeding, significant
      increases in antral mRNA level were detected in 1 h, and peak levels were reached
      by 2 h (more than two times higher than starved control). There was a rapid and
      significant decrease in progastrin immunoreactivity within 30 min, followed by a
      significant increase in gastrin immunoreactivity 2 h after refeeding. These data
      suggest that rapid increases of blood and tissue gastrin levels in response to
      food may be associated with increases in both gastrin gene expression and post
      translational processing of progastrin.

PMID- 1974755
TI  - Corticotropin-releasing factor.

PMID- 1974756
TI  - Application of intragenic DNA probes in prenatal screening for retinoblastoma
      gene carriers in the United Kingdom.
AB  - Restriction fragment length polymorphisms (RFLPs) in 55 families affected by
      retinoblastoma have been studied using recombinant DNA probes derived from within
      the retinoblastoma predisposition gene. Only six families were uninformative for
      any of the DNA polymorphisms. The remaining 49 families can be offered prenatal
      screening. No obligate recombinations between any of the polymorphic loci and the
      retinoblastoma phenotype were observed. Four previously unknown cases of non
      penetrance were identified. Prenatal testing for the inheritance of mutant
      alleles was performed in two cases and perinatal screening in two additional
      cases. One fetus inherited the normal allele from the affected parent and is
      therefore not at risk of retinoblastoma; the second fetus inherited the mutant
      allele and will require frequent screening for early detection of retinoblastoma.
      Both perinatal tests showed the absence of the mutant allele.

PMID- 1974758
TI  - [A modification of Grimelius' method for the identification of apudocytes on
      semithin sections].
AB  - Modified Grimelius method of the apudocyte identification on the semithin
      sections is described and used for the study of the duodenum endocrine cells. The
      method gives the possibility to study the distribution of secretory granules in
      the endocrine cell cytoplasm and increases the possibilities of taking samples
      for the ultrastructural analysis of apudocytes.

PMID- 1974757
TI  - Regional alterations of brain biogenic amines and GABA/glutamate levels in rats
      following chronic lead exposure during neonatal development.
AB  - Wistar rat pups were administered either a high dose of lead acetate (400
      micrograms lead/g body weight/day) or a low dose (100 micrograms lead/g body
      weight/day) by gastric intubation, from 2 days through 60 days of age. The rats
      on both these doses exhibited statistically significant decreases in body and
      brain weights throughout the lead treatment period. A group of rats on high dose
      was also rehabilitated by discontinuing the lead from 60 days of age. In these
      rats, at 160 days of age, the body weight but not the brain weight recovered to
      normal levels. During the lead intake, the rats on high dose revealed significant
      elevations in the levels of noradrenaline (NA) in the hippocampus (HI),
      cerebellum (CE), hypothalamus (HY), brainstem (BS), and accumbens-striatum (SA).
      The elevated levels in all the above regions except in the HY persisted even
      after rehabilitation. The dopamine (DA) levels changed significantly in opposite
      directions in HY (elevation) and BS (reduction) during the lead treatment, and
      the HY recovered after rehabilitation. Under lead, the serotonin (5HT) levels
      were elevated significantly in the HI, BS and MC (motor cortex), while after
      rehabilitation the abnormality persisted only in the MC. Low dose lead treatment
      was also effective on the same areas of brain. In the low dose group, estimation
      of the levels of GABA and glutamate were also done, and a significant decrease of
      GABA in CE and glutamate in MC was observed. The differences observed in the
      neurotoxic effects (none or significant) of lead in the different regions for
      each of the transmitters (NA, DA, 5HT) supports the interesting conclusion that
      the vulnerability of the axon terminals of any given type is dependent on some
      regional factors, although the projections of the different regions originate
      from an apparently similar category of neurons in the brain stem.

PMID- 1974759
TI  - Adenosylcobalamin-dependent methylmalonyl-CoA mutase from Propionibacterium
      shermanii. Active holoenzyme produced from Escherichia coli.
AB  - The linked structural genes coding for both subunits of adenosylcobalamin
      dependent methylmalonyl-CoA mutase from the Gram-positive bacterium
      Propionibacterium shermanii have been altered by site-directed mutagenesis and
      placed under the control of an inducible phage-T7-specific plasmid promoter in
      Escherichia coli. Conditions have been found under which both alpha- and beta
      subunits are produced in soluble form, in near 1:1 ratio, and assemble to form
      apo-mutase totalling about 5% of the total cellular protein. Methylmalonyl-CoA
      mutase purified from these cells could be readily converted into the holoenzyme
      by addition of adenosylcobalamin. The active holoenzyme apparently crystallizes
      in the same space group as an inactive corrinoid-containing form of the enzyme
      obtained previously.

PMID- 1974760
TI  - Immunological analysis of acetyl-CoA carboxylase mass, tissue distribution and
      subunit composition.
AB  - Changes in the mass and subunit structure of liver acetyl-CoA carboxylase (ACC)
      accompany altered nutrition in vivo. Enzyme activity in different tissues and
      cell lines is also, in part, determined by variations in both total mass and ACC
      isoenzyme composition. ACC isoenzyme mass and hetero/homo-isoenzyme association
      were quantified by three sandwich e.l.i.s.a. assays, i.e. an avidin-based assay
      that measured total isoenzyme mass and two antibody-sandwich assays which measure
      polypeptide association. Results from the avidin-based assay reveal that the two
      major isoenzymes, of molecular mass 265 kDa (ACC 265) and 280 kDa (ACC 280), are
      present in markedly variable concentration in several rat and mouse tissues and
      in cell lines of rat and mouse origin. Hepatic ACC mass has been reported to be
      distributed between mitochondrial and cytosolic fractions and to undergo only a
      change in subcellular distribution without alteration in total mass on
      induction/repression of activity in vivo [Roman-Lopez, Shriver, Joseph & Alfred
      (1989) Biochem. J. 260, 927-930]. However, in the present study, immunoblotting
      and e.l.i.s.a. analysis reveals that, in rat liver, the mass of both isoenzymes
      is predominantly cytosolic in distribution, is markedly diminished on fasting and
      rises 6-8-fold on refeeding of a high-carbohydrate diet. These data support the
      results of several other investigations of hepatic ACC mass, and are consistent
      with known nutritionally altered changes in ACC mRNA content. By the two antibody
      sandwich e.l.i.s.a. assays, isoenzyme complexes either composed of both ACC 280
      and 265 or with multiple copies of ACC 265 are detectable in rat liver enzyme;
      their concentration varies independently of total ACC mass with the nutritional
      state of the rat, being lowest in fasting and highest on fasting/refeeding.
      E.l.i.s.a. analysis, applicable to crude tissue/cell extracts, provides a simple,
      sensitive and quantitative measurement of ACC mass and subunit composition. Its
      use may permit needed quantitative insight into the role of variable total ACC
      and isoenzyme mass and of alterations in ACC subunit composition that occur in
      vivo or in isolated cells in response to a variety of hormonal and nutritional
      influences.

PMID- 1974761
TI  - Regulation of beta-adrenergic responsiveness during erythroid differentiation of
      Friend erythroleukemia cells.
AB  - Mouse erythroblastoma cells were used as a model system to study sensitivity and
      regulation of the beta-adrenergic system during DMSO-induced differentiation from
      the proerythroblast to the normoblast stage. Differentiation was characterized by
      a initial marked increase in hormonal sensitivity lasting 24 to 40 h followed by
      a gradual loss of beta-adrenergic responsiveness. These changes are mainly due to
      a rapid but transient increase in receptor density (4 fold) and a marked shift of
      the membrane concentrations of the transmembrane signalling proteins Gs and Gi.
      The Gs to Gi ratio changed from 1:7 in native MEL cells to 2:1 in differentiated
      cells. By contrast, fusion experiments between rat reticulocytes and and MEL
      cells indicated that cytosolic factors, while not prominently involved in the
      regulation of the beta-adrenergic system of differentiating MEL cells, may be
      responsible for the rapid loss of cyclase activity during reticulocyte
      maturation, the last step in red cell formation.

PMID- 1974762
TI  - On the fundamental difference in the thermodynamics of agonist and antagonist
      interactions with beta-adrenergic receptors and the mechanism of entropy-driven
      binding.

PMID- 1974763
TI  - Effects of alpha 2-adrenergic agonist preincubation on subsequent forskolin
      stimulated adenylate cyclase activity and [3H]forskolin binding in membranes from
      HT29 cells.
AB  - alpha 2-Adrenergic agonist preincubation resulted in a leftward shift in the
      subsequent concentration-response curve to forskolin-stimulated adenylate cyclase
      activity in membranes from HT29 cells, a human colon adenocarcinoma cell line.
      This effect was much less pronounced than the effect seen in the intact cell
      cyclic AMP production assays. Removal of GTP from the assay caused a further
      slight leftward shift in the concentration-response curve. In [3H]forskolin
      binding experiments, alpha 2-adrenergic agonist preincubation caused a doubling
      of the maximal number of binding sites (80 vs 31 fmol/mg protein) compared to
      control. The addition of MgCl2 and NaF to the assay buffer increased control
      binding 5-fold. With agonist preincubation, there was a further increase in
      binding in the presence of MgCl2 and NaF which was not significantly different
      from the appropriate control. Pertussis toxin pretreatment blocked both the
      leftward shift in the forskolin concentration-response curve and the increase in
      maximal number of binding sites, indicating that a pertussis toxin sensitive
      protein is involved in these changes. Activation of cyclic AMP production in the
      intact cell by cholera toxin followed by norepinephrine preincubation and then
      stimulation by forskolin resulted in a degree of sensitization similar to that
      seen in the membrane adenylate cyclase and binding assays. Pertussis toxin also
      blocked this sensitization. It appears that if the cyclase system is highly
      activated, then the degree of sensitization is similar in the membrane and intact
      cell assay.

PMID- 1974764
TI  - Defective signal transduction--a common pathway for cellular dysfunction in HIV
      infection?
AB  - Qualitative defects in immune responsiveness after human immunodeficiency virus
      (HIV) infection have been well characterized and may play a key role in the
      development of HIV disease. However, no clear picture of the underlying mechanism
      of the functional deficiencies has yet emerged. In this article, Anthony Pinching
      and Keith Nye suggest that HIV or HIV proteins can sabotage transmembrane
      signalling and that this is of primary importance to the alterations in immune
      responsiveness.

PMID- 1974765
TI  - T-cell subset alterations and lymphocyte responsiveness to mitogens and antigen
      during severe primary infection with HIV: a case series of seven consecutive HIV
      seroconverters.
AB  - Seven consecutive patients who presented with a severe acute mononucleosis-like
      illness associated with HIV seroconversion were evaluated by T-cell subset
      enumerations and measurements of lymphocyte transformation responses to mitogens
      and antigen during both their primary illness and a 1-year follow-up period. We
      observed a characteristic pattern of response to primary HIV infection; initial
      lymphopenia was followed by CD8 lymphocytosis and inversion of the CD4:CD8 ratio.
      During follow-up, the CD8 count gradually returned to normal, whereas the CD4:CD8
      ratio remained inverted because of a relatively low number of CD4 lymphocytes.
      Primary infection was followed by prolonged and severe cellular
      hyporesponsiveness to both mitogens and antigen. At the last follow-up, responses
      to pokeweed mitogen were still severely impaired, with a median 19% (range 7-50%)
      of that observed in healthy controls. We conclude that severe primary HIV
      infection may be followed by sustained lymphocyte hyporesponsiveness, a sustained
      low percentage of CD4 lymphocytes and sustained inversion of the CD4:CD8 ratio.

PMID- 1974766
TI  - Productive infection of both CD4+ and CD4- human cell lines with HIV-1, HIV-2 and
      SIVagm.
AB  - Human monolayer cells of various origins were shown to be susceptible to
      infection by HIV-1, HIV-2 and simian immunodeficiency virus obtained from African
      green monkeys (SIVagm). Immunoperoxidase staining revealed infection of 2-7% of
      the monolayer cells, although in order to achieve infection approximately 50-fold
      more virus was necessary than with CD4(+)-permissive lymphoma cells. No CD4
      receptor antigen expression by fibroblastoid cells was detectable by
      immunofluorescence using several monoclonal antibodies (MAbs), although a low
      level of CD4-specific messenger RNA expression was revealed by Northern analysis
      (with the exception of Tera-1 and RD cells). Attempts to block viral infection by
      anti-CD4 MAbs indicated a CD4 receptor-mediated mechanism for all lines tested
      except RD cells. We conclude that a low level of CD4-receptor expression is
      sufficient to allow infection of fibroblastoid cells. The infectability of a CD4
      negative cell line indicates a second pathway of cellular infection, possibly
      mediated by a cellular receptor distinct from the CD4 molecule.

PMID- 1974767
TI  - Characterization of a putative cellular receptor for HIV-1 transmembrane
      glycoprotein using synthetic peptides.
AB  - The transmembrane glycoprotein (gp41 or TM) of HIV-1 contains limited sequence
      similarity to TM of some immunosuppressive animal retroviruses. A specific HIV-1
      TM sequence, denoted CS3, inhibits T-cell activation in vitro and antibody
      specific to CS3 has been linked to the absence of disease. CS3, when conjugated
      to human serum albumin (HSA) and labeled with fluorescein, binds specifically to
      CD4+ cell lines. Cross-linking of CS3-HSA to its binding activity on the CD4+
      cell line RH9 reveals a putative subunit size of approximately 44 kD. Incubation
      of RH9 cells with CS3-HSA prior to addition of HIV-1 prevented HIV-1-mediated
      cell lysis and inhibited infection. These results suggest that the CS3 region of
      TM plays an important role in the pathogenesis of the AIDS virus, HIV-1.

PMID- 1974768
TI  - Beta adrenergic blocking medications for aggressive or self-injurious mentally
      retarded persons.
AB  - The psychopharmacologic treatment of persons with mental retardation who exhibit
      aggressive or self-injurious syndromes is varied and controversial. Many
      psychotropic agents (e.g., antipsychotics, benzodiazepines, lithium,
      psychostimulants, anticonvulsants, and narcotic antagonists) have been used;
      currently, none of these have been studied sufficiently to recommend them
      unequivocally, and most have serious potential side effects. A new group of
      medications, blockers of the beta-adrenergic function of the sympathetic nervous
      system, have been postulated to have efficacy in some aggressive or self
      injurious persons. This literature was reviewed, a relevant case report
      presented, and concerns raised regarding premature endorsement of beta-blocking
      medications before they have been adequately studied.

PMID- 1974769
TI  - Enteric bacteria and osmotic stress: intracellular potassium glutamate as a
      secondary signal of osmotic stress?
AB  - Enteric bacteria have evolved an impressive array of mechanisms that allow the
      cell to grow at widely different external osmotic pressures. These serve two
      linked functions; firstly, they allow the cell to maintain a relatively constant
      turgor pressure which is essential for cell growth; and secondly they permit
      changes in cytoplasmic composition such that the accumulation of intracellular
      osmolytes required to restore turgor pressure does not impair enzyme function.
      The primary event in turgor regulation is the controlled accumulation of
      potassium and its counterion glutamate. At high external osmolarities the
      cytoplasmic levels of potassium glutamate can impair enzyme function. Rapid
      growth is therefore dependent upon secondary responses, principally the
      accumulation of compatible solutes, betaine (N-trimethylglycine), proline and
      trehalose. The accumulation of these solutes is achieved by the controlled
      activity of transport systems and enzymes in response to changes in external
      osmotic pressure. It has been proposed that the accumulation of potassium
      glutamate during turgor regulation acts as a signal for the activation of these
      systems [1,2]. This brief review will examine the evidence that control over the
      balance of cytoplasmic osmolytes is achieved by sensing of the intracellular
      potassium (and glutamate) concentration.

PMID- 1974770
TI  - Unconventional vertebrates as models in endocrine research. A symposium. December
      5-6, 1988, Bethesda, Maryland. Proceedings.

PMID- 1974772
TI  - Reptilian and avian follicular hierarchies: models for the study of ovarian
      development.
AB  - The presence of an ovarian follicular hierarchy is a characteristic feature of
      reptiles and birds. The hierarchy contains follicles at all stages of maturation
      and therefore, varying degrees of sensitivity to the ovulation-inducing effects
      of the gonadotropins. In the hen, ovulability is gained as the ability of the
      follicle to produce androgens and estrogens declines and the ability to produce
      progesterone increases. In the mature follicle, the granulosa cells are the site
      of progesterone production whereas the theca cells produce androgens and
      estrogens. Small follicles that have not yet been (and may never be) recruited
      into the yolk-filled hierarchy are the major producers of androgens and estrogens
      within the ovary. In reptiles the ovarian follicular hierarchy includes non
      vitellogenic follicles and in some species includes follicles destined to become
      atretic. These two features distinguish the reptiles from the birds and provide
      experimental biologists with a unique model to investigate the physiological
      events that regulate the most common fate of ovarian follicles, atresia.

PMID- 1974771
TI  - Vitellogenesis in reptiles as a model for mammalian sex-differentiated hepatic
      protein synthesis.
AB  - The stimulation of yolk protein synthesis by estrogen is a characteristic of
      female non-mammalian vertebrates; in mammals, or their reptilian ancestors,
      however, vitellogenesis has been suppressed as a corollary of the evolution of
      viviparity. It is our hypothesis that progesterone has a dual role in this
      phylogenetic trend: a) to inhibit myometrial contraction and thus set the stage
      for internal development of embryos and associated placentation and b) to inhibit
      yolk protein synthesis in a coordinate manner as placentation became an efficient
      direct supply of nutrients to the fetus. Despite the absence of vitellogenesis
      per se in eutherian mammals, significant sex-differentiated hepatic protein-lipid
      synthetic functions remain, which are under complex hormonal control. We have
      presented evidence that in the reptiles, the central vertebrate group from which
      the ancestors of modern mammals evolved, the control of yolk protein synthesis is
      also complex, involving both pituitary hormones (GH, PRL, and LH) and ovarian
      steroids (estradiol, testosterone, and progesterone). Adequate evidence exists to
      suggest that mammalian hepatic lipoprotein synthesis and its regulatory elements
      are phylogenetically derived from their reptilian ancestors and may be better
      understood in this context. This is of particular relevance to cardiovascular
      disease in which there is a clear sex bias yet for which no coordinated research
      program exists which takes into account the relevant phylogenetic history. We
      believe that reptilian, and possibly avian, models could be used to great
      advantage to probe the endocrine components of cardiovascular disease.

PMID- 1974774
TI  - Teleost model for studying the effects of chemicals on female reproductive
      endocrine function.
AB  - The effects of several mammalian reproductive toxins on reproductive endocrine
      function in female Atlantic croaker (Micropogonias undulatus) were examined.
      Croaker were exposed to sublethal concentrations of lead, cadmium, benzo[a]pyrene
      (BaP), or a polychlorinated biphenyl mixture (Aroclor 1254) for 1 month during
      the period of ovarian recrudescence. Reproduction was altered after exposure to
      all four chemicals. The plasma levels and secretion rates of reproductive
      hormones were augmented after exposure to cadmium resulting in precocious ovarian
      growth. In contrast, treatment with lead, BaP, or Aroclor 1254 caused a decline
      in circulating steroid hormone levels and ovarian growth. Changes in hormone
      secretion rates from isolated pituitary and ovarian tissues incubated in vitro
      were also observed after exposure to several of the reproductive toxins. It is
      concluded that the Atlantic croaker is a sensitive model for examining the
      effects of reproductive toxins on female reproductive endocrine function. Our
      results indicate that these chemicals may act at various sites on the
      hypothalamus-pituitary-gonadal axis to alter reproductive endocrine function.

PMID- 1974773
TI  - Channel catfish as an unconventional model for immunological studies.
AB  - The channel catfish, Ictalurus punctatus, is an economically important species
      which is readily available, acclimates well to the laboratory setting, and is
      amenable to considerable experimental manipulation. Although the channel catfish
      is still a relatively circumscribed species in terms of comprehensive physiologic
      and/or endocrinologic studies, our current understanding of the basic
      immunobiology and immunochemistry of the channel catfish is significantly further
      advanced than for any other teleost species. In this respect the channel catfish
      is not only proving useful in the general areas of comparative immunology but it
      is also showing considerable promise as a model system for definitive studies on
      problems which bridge the fields of immunology and endocrinology, i.e.,
      understanding the effects of environmental temperature and stress on the immune
      system.

PMID- 1974775
TI  - Sex-changing fish as a manipulable system for the study of the determination,
      differentiation, and stability of sex in vertebrates.
AB  - Two fundamental questions concerning vertebrate sexuality are what controls the
      stability of gender throughout the life of an individual and what are the
      genetic, immunological, and endocrine factors controlling sex determination and
      differentiation. Significant aspects of both issues cannot readily be examined
      experimentally in standard laboratory vertebrates partly because these species
      are gonochores and provide no opportunity to examine plasticity in sexual
      systems, and partly because few means have yet been found experimentally to
      manipulate immunogenetic factors, such as sex-specific DNA or cell-surface
      antigens, thought to be involved in the determination and differentiation of sex.
      Behaviorally induced adult sex change in hermaphroditic fishes constitutes a
      unique system of controlled sexual plasticity in which these issues can be
      addressed. Several species of tropical marine fishes satisfy the requirements for
      an appropriate laboratory experimental animal. Sex change in them is known to
      involve alterations in external coloration, behavior, gonadal structure, hormonal
      enzyme activity, levels of circulating steroid hormones, and concentrations of H
      Y antigen. Genetic, immunological, endocrine, and behavioral factors interact
      with one another causally in ways permitting relatively simple manipulations
      simultaneously to analyze the network of sequential causes for sex change and to
      address the above-stated fundamental issues concerning sexuality generally in
      vertebrates. Since sex change can be started at will, these fish species become
      powerful model systems for the analysis of basic mechanisms of sex determination,
      differentiation, and long-term stability.

PMID- 1974776
TI  - Cyclostome models for speculation on evolution of vertebrate endocrine systems.

PMID- 1974778
TI  - Mexican leaf frog (Pachymedusa dacnicolor) as a model in endocrine research.

PMID- 1974777
TI  - Shark testis model: stage-dependent functions and the regulation of
      spermatogenesis.
AB  - In mammals, a single Sertoli cell nurtures 3-4 successive generations of germ
      cells. Thus, it is not possible to study this cell type at a single spermatogenic
      stage. In the dogfish shark Squalus acanthias, a single cohort of Sertoli cells
      remains associated with a germ cell clone throughout its development. Moreover,
      different germ cell stages are topographically segregated within the testis and
      can be easily staged by transilluminationmicroscopy. Recently, we have developed
      methods for the isolation and culture of spermatocysts (Sertoli/germ cell units)
      and Sertoli cells only from pre-meiotic, meiotic, and post-meiotic stages of germ
      cell development. Here, we present data that illustrate the feasibility of using
      the Squalus testis model for characterizing stage-related biochemical changes in
      Sertoli cells.

PMID- 1974779
TI  - Amphibian experimental systems: developmental neurobiology and behavioral
      endocrinology in the clawed frog, Xenopus laevis.

PMID- 1974780
TI  - Developmental changes in the processing of ACTH in the anterior pituitary of the
      amphibian, Ambystoma tigrinum.
AB  - Acid extracts of anterior pituitaries obtained from larval, neotene,
      postmetamorphic young adult, and sexually active adult Ambystoma tigrinum were
      fractionated by gel filtration and analyzed by RIA. In larval, neotene, and
      postmetamorphic adults the molar ratio of ACTH(1-39) to alpha-MSH was,
      respectively, 1.3:1, 1:1.3, and 1:1.3. However, in sexually mature adults the
      molar ratio of ACTH(1-39) to alpha-MSH was 8:1. These results indicate that prior
      to and immediately after metamorphosis, both ACTH(1-39) and alpha-MSH are major
      end products of corticotropic cells in this species. As postmetamorphic animals
      reach sexual maturity, there is a shift in the processing of ACTH which yields
      ACTH(1-39) as the major end product of corticotropic cells. In the corticotropic
      cells of adults only trace amounts of alpha-MSH are produced.

PMID- 1974781
TI  - Amphibian model system for problems in behavioral neuroendocrinology.

PMID- 1974782
TI  - Hypothalamo-pituitary axes and feedback control in amphibians and reptiles.

PMID- 1974784
TI  - Psychobiology of reptilian reproduction.
AB  - The key to understanding species variation in neuroendocrine controlling
      mechanisms lies in understanding the constraints that have given rise to diverse
      reproductive patterns. Recent research clearly shows that species evolving under
      different constraints exhibit different patterns of reproduction and have
      fundamentally different neuroendocrine mechanisms controlling reproduction.
      Diversity can be exploited profitably by those interested in the fundamental
      nature of biobehavioral mechanisms. The comparative approach also promises to
      increase our understanding of broader intellectual and theoretical issues in
      behavioral endocrinology.

PMID- 1974783
TI  - Reptilian embryos: a model for sex determination and sexual differentiation in
      amniotes.

PMID- 1974785
TI  - Iguana iguana: a model species for studying the ontogeny of behavior/hormone
      interactions.
AB  - Several features of the green iguana, Iguana iguana, make this species an
      excellent subject for biological research, especially with respect to collecting
      comparative data on behavior/hormone interactions. This species thrives on
      captivity, and behavioral interactions appear substantially similar to those
      observed in natural populations, given effective captive environments. Because
      hatchlings do not necessarily associate with adult conspecifics in wild
      populations, behavioral patterns exhibited by and among juveniles in either
      natural conditions or captivity are probably unlearned behaviors. The species is
      large enough to obtain blood samples at frequent intervals at an early age.
      Because the species is herbivorous the maturation process can be controlled by
      the caloric base made available to individual lizards.

PMID- 1974787
TI  - Parthenogenetic lizards as vertebrate systems.
AB  - Unisexual (all-female) lizards of the genus Cnemidophorus are well suited for
      research in oogenesis, embryogenesis, nutrition, immunology, sex determination,
      genetics and the effects of aging and exposure to pathogens and chemicals, in
      addition to evolutionary biology. Individuals produce clones by means of
      parthenogenesis, and both diploid and triploid parthenogens exist. In addition,
      there are closely related bisexual (gonochoristic) species of Cnemidophorus.
      Advantages and disadvantages of maintaining laboratory colonies of Cnemidophorus
      are discussed.

PMID- 1974788
TI  - The avian embryo as a model for early developmental endocrinology.
AB  - Studies utilizing the developing chicken embryo have significantly augmented our
      understanding of the ontogeny of endocrine regulation during major critical
      periods of embryonic development. These embryos currently provide the only
      available models for elucidating the onset of endocrine function during all
      stages of in situ amniote development, for examining chronic calcium deficiency
      during embryogenesis, and for experiments in basic renal function during periods
      when only the mesonephros is normally functioning, as well as mixed
      meso/metanephric function and solely metanephric kidney function.

PMID- 1974786
TI  - Neuroendocrine regulation of seasonal breeding cycles in the ewe.
AB  - Seasonal reproduction has emerged as an important topic of investigation which
      bridges the areas of endocrinology, neurobiology, biological rhythms, and
      fertility regulation. Among the species in which this topic has been studied, the
      sheep has proven to be especially useful for investigating the neuroendocrine
      mechanisms which underlie the seasonal switches in fertility. This is due to a
      number of attributes. One of these is the large blood volume of sheep which
      permits extensive sampling for characterizing pulsatile patterns of hormone
      secretion. Another attribute is the large size of its brain and pituitary gland
      which facilitates complex neurosurgical procedures such as those required for
      collecting hypothalamic-pituitary portal blood for measurement of
      hypophysiotropic substances. Based on work in sheep, it has become evident that
      pulsatile secretion of luteinizing hormone (LH) from the anterior pituitary is
      driven by an episodic discharge of gonadotropin-releasing hormone (GnRH) from the
      hypothalamus, and that seasonal reproduction results largely from alterations in
      the pulsatile pattern of LH release. By using the sheep as a model, it should now
      be possible to elucidate the neural mechanisms which underlie these seasonal
      alterations in the reproductive neuroendocrine axis.

PMID- 1974789
TI  - Recent findings on the development of dimorphic anatomy in the avian song system.
AB  - Much current research in neuroendocrinology concerns how endocrine information
      acts on the brain. For example, what processes are used early in life to
      transduce sex differences in gonadal steroids into structural dimorphisms within
      the brain? Or, to what extent are the actions of steroids on the developing
      nervous system unique events and to what extent are they a continuing part of the
      interplay between the endocrine and the central nervous system? The avian song
      system has proven to be a very useful model system in which to study these
      issues. Recent research from my laboratory on the development of sex differences
      in brain structure and on steroid-related adult plasticity is reviewed below.
      This review is quite focussed. More general reviews of research on the song
      system can be found in Arnold ('89), DeVoogd ('86), Konishi ('85), and Nottebohm
      ('88).

PMID- 1974790
TI  - Insulin and insulin-like growth factor I action in the chick embryo: from biology
      to molecular endocrinology.

PMID- 1974791
TI  - The avian ovary: model for endocrine studies.

PMID- 1974792
TI  - "Paradoxical" growth hormone secretion in acromegaly: an avian model?
AB  - Acromegaly is a pathological human condition resulting from an excess of growth
      hormone (GH) secretion in adults. The regulation of GH secretion in acromegalics
      is characterised by "paradoxical" GH responses to dynamic tests of pituitary GH
      function. Many of these "paradoxical" responses appear to be normal,
      physiological GH responses in aves. Comparative studies on the control of GH
      secretion in immature birds may therefore provide an experimental model for
      testing the effects of therapeutic agents of GH secretion.

PMID- 1974793
TI  - Unconventional organisms as models in biological research.
AB  - The use of unconventional organisms in experimental research is a timely subject
      that impacts upon current science policy in the areas of animal welfare,
      biodiversity, and biotechnology. Many recent reports have recommended a reduction
      in the use of mammals in biomedical research to promote animal welfare by
      utilizing alternative methods and unconventional model organisms. Currently we
      lack adequate models for all the biological phenomena worthy of study. Biologists
      must continue to take advantage of the functional biodiversity of organisms not
      only to identify new model organisms for studying more optimally those life
      processes we know something about, but also to discover entirely new biological
      principles, processes, and products. Increased emphasis on the need to preserve
      the diversity of life also requires more knowledge of the comparative biology of
      processes such as reproduction, growth, defense mechanisms, and nutrition. The
      functional biodiversity of life can be exploited not only for fundamentally new
      biological insights, but also for expanding the knowledge base needed for
      commercial biotechnology. There is a critical need of commercial biotechnology
      for basic functional information on more species, especially microorganisms and
      plants. The knowledge of biodiversity will mean little to most of mankind unless
      the motivation exists to use it for commercial benefit.

PMID- 1974794
TI  - Maternal programming of the fetal brain dictates the response of juvenile
      Siberian hamsters to photoperiod: dissecting the information transfer system.
AB  - Development of neuroendocrine mechanisms regulating reproduction results from the
      interaction between genetic and environmental factors. For the developing fetus,
      the environment includes the maternal system. Our work with Siberian hamsters
      examines mechanisms by which prenatal photoperiods influence neuroendocrine
      functions regulating postnatal reproductive development. The maternal system has
      two effects on the young: 1) to program a reproductive growth pattern in the
      young and 2) to influence the ability of the young to respond to photoperiods
      encountered after weaning. Three paradigms have been used to study the role of
      the pineal hormone melatonin in this process. Injection of pregnant females with
      melatonin or removing melatonin has demonstrated that the maternal pineal is
      required for the transference of photoperiodic information to fetuses. However,
      when pregnant females receive continuous release implants of melatonin the
      effects of melatonin on fetuses are dependent on gestational photoperiod,
      suggesting that while melatonin is necessary it is not the only component in the
      mechanism for the transference of photoperiodic information to fetuses.

PMID- 1974795
TI  - Endocrine correlates of hibernation-independent gonadal recrudescence and the
      limited late-winter breeding season in woodchucks, Marmota monax.
AB  - Woodchucks (Marmota monax) normally experience gonadal recrudescence towards the
      end of a 4-5 month hibernation, emerge in late winter, immediately breed in a
      short 3-week breeding season, and have regressed gonads before the next
      hibernation. Our studies of wild and captive animals show that fertile females
      give birth to single litters after a 32-day gestation and their breeding season
      is terminated by a reactivation of the corpora lutea of pregnancy for 1-3 months
      immediately postpartum. In nonbred females the breeding season is likewise
      terminated by spontaneous luteinization of the ovaries for 1-3 months shortly
      after the vernal equinox. Tests regress and testosterone declines during and
      after the breeding season. Circannual reproductive cycles persist in the absence
      of hibernation and are shortened to 9-10 months after 3-5 years of a 12L:12D
      photoperiod. Unique aspects of this species that merit endocrine investigation
      include descent/retraction of testes, transient luteolysis at parturition,
      superactivation of postpartum corpora lutea, regulation of the pituitary-gonadal
      axis by an annual endogenous metabolic cycle entrained to the annual change in
      photoperiod, and the hormonal basis of hibernation.

PMID- 1974796
TI  - The musk shrew, Suncus murinus, a unique animal model for the study of female
      behavioral endocrinology.
AB  - Insectivora is the third largest mammalian order, composed of a number of unusual
      species considered to be the most primitive of the modern eutherian mammals. Yet,
      little is known about the members of this evolutionarily unique and important
      group. The musk shrew (Suncus murinus) is a convenient and practical laboratory
      animal. The study of the reproductive biology of this species will yield needed
      comparative data. Moreover, the little information that we have collected on this
      species suggests that several unusual characteristics make this animal a
      worthwhile and novel model for endocrine research. Most of the current and past
      research on this species has focused on the endocrinology of the female musk
      shrew. Unlike conventional small mammal models, the female musk shrew has no
      spontaneous ovarian cycle. The ovaries of the adult, unmated female do not
      undergo spontaneous follicular development. At the time of mating only small,
      relatively immature follicles are present. As a consequence, ovarian hormone
      production is not cyclic. Thus, traditional hormone target tissues such as the
      vaginal epithelium and the uterus do not exhibit cycles in cell proliferation.
      Sexual behavior is likewise demonstrated in an acyclic manner. Virgin females
      become sexually receptive within minutes after their first exposure to a male,
      and nonpregnant females are virtually always sexually receptive. Sexual
      receptivity in the virgin female musk shrew occurs in the face of relatively low
      plasma estradiol levels and higher androgen levels, and does not appear to be
      mediated via ovarian estradiol. Instead, recent work suggests that close to
      physiological doses of testosterone can restore sexual behavior in ovariectomized
      musk shrews.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1974798
TI  - The ferret as a model for studying the sexual differentiation of behavioral and
      reproductive function.

PMID- 1974797
TI  - The black mastiff bat (Molossus ater): a novel, mammalian model for studies of
      ovarian, uterine, and placental biology.
AB  - The reproductive biology of the black mastiff bat has been examined using animals
      maintained in a laboratory colony. Ovulation was found to be spontaneous and
      occurred only from the right ovary. The corpora lutea appeared to be functional,
      and decidual reactions developed in the uterus during the luteal phase of the
      cycle even in the absence of an implanting blastocyst. At the end of nonpregnant,
      ovulatory cycles much of the endometrium became necrotic and was desquamated with
      associated bleeding. In the event of pregnancy only a single blastocyst implanted
      in the right uterine horn, and the discoidal chorioallantoic placenta then
      developed at the cranial end of that horn. This was preceded by the development
      of an unusual vascular tuft in the endometrium in that region. The endothelial
      cells of the tuft vessels became hypertrophied during early pregnancy and
      developed more prominent basal laminae. Trophoblast then grew preferentially
      around these vessels. These observations suggest that factors secreted by
      endometrial endothelial cells and incorporated at least in part into their basal
      laminae may play a central role in controlling early trophoblastic growth during
      the morphogenesis of the discoidal chorioallantoic placenta in this bat.

PMID- 1974799
TI  - Use of urinary hormone assays for evaluating endocrine patterns associated with
      the long-day breeding season in Eld's deer (Cervus eldi).
AB  - Reproductive seasonality and pregnancy in the endangered brow-antlered or Eld's
      deer (Cervus eldi) were studied by measuring urinary estrone conjugates (EC) and
      pregnanediol-3 alpha-glucuronide (PdG) profiles in voided urine. Based on the
      excretion of PdG, female Eld's deer were seasonally polyestrous, spontaneous
      ovulators with regular cyclic activity beginning in January to March and ending
      in August to October. The overall estrous cycle averaged 21.5 +/- 2.1 days (+/-
      SEM, n = 65); however, 2 of 13 does consistently produced prolonged cycles (30.1
      +/- 4.4 days, n = 14). Behavioral estrus (approximately 12-24 h duration) was
      observed in 42 of 65 cycles and always occurred when PdG excretion was at nadir
      levels. In two does that were serially bled, preovulatory plasma LH peaks
      occurred coincident with estrus, and progesterone secretion paralleled PdG
      excretion. Mean gestation duration (n = 10) was 33.5 +/- 0.4 wk with PdG
      concentrations increasing markedly during pregnancy (especially the last 25 wk)
      before an abrupt decline coincided with parturition. Mean EC excretion remained
      low during much of gestation; however, significant increases in this metabolite
      were observed, particularly during the 4 wk immediately preceding parturition.
      The results are the first to demonstrate the utility of atraumatic urinary
      hormone monitoring for studying the endocrinology of cervids. Excreted urinary
      PdG accurately reflects circannual fluctuations in cyclic ovarian activity, and
      longitudinal increases in this metabolite are highly indicative of pregnancy.
      Cyclic ovarian activity cannot be clearly monitored by urinary EC concentrations,
      although this metabolite can be used in conjunction with elevated PdG levels to
      confirm pregnancy and perhaps estimate the onset of impending parturition.

PMID- 1974800
TI  - The passerine bird song system as a model in neuroendocrine research.
AB  - In the neural system controlling song in passerine birds, gonadal steroid
      hormones have potent effects on neural growth and differentiation. During
      ontogeny, sex differences in the secretion of steroid hormones lead to dramatic
      sex differences in neuron number and structure. In adulthood, sex steroid
      hormones also cause a significant reorganization of neural circuits. These
      studies of hormone action have been influential in the development of the field
      of neuroendocrinology.

PMID- 1974801
TI  - Recognition by goby intestine of a somatostatin analog, SMS 201-995.
AB  - The caudal neurosecretory peptide urotensin II and its partial structural analog
      the hypothalamic and gastroenteropancreatic peptide somatostatin can be
      distinguished by the goby posterior intestine; urotensin II stimulates Na+ and Cl
      absorption whereas somatostatin is without effect. Sandostatin (Sandoz compound
      SMS 201-995) is a partial structural analog of somatostatin, possessing the
      active core common to both urotensin II and somatostatin but lacking the C- and N
      terminal tails which apparently confer recognition in species specificity. SMS
      201-995 mimicked the effects of urotensin II, namely, increased net Cl-
      absorption and decreased radiochloride backflux consistent with the observed
      increase in transepithelial resistance and the cellular depolarization typical of
      transport stimulation in this tissue. Speculation on the role of the tails in
      species-specific recognition is supported by the nature of amino acid residue
      substitutions in urotensin II, somatostatin, and SMS 201-995 and suggests the
      existence of multiple receptor types for this group of peptides.

PMID- 1974802
TI  - The avian as an animal model for the study of the vitamin D endocrine system.
AB  - This paper presents a summary of experimental studies which utilized the White
      Leghorn cockerel, Gallus domesticus, as a suitable avian model for a detailed
      analysis of the mode of action of the seco-steroid vitamin D. It is now apparent
      that there exists a complex endocrine system which coordinates the metabolism of
      the parent vitamin D into a family of over 30 metabolites; the principal
      metabolites are 1,25(OH)2D3 and 24R,25(OH)2D3, which together orchestrate the
      spectrum of biological responses attributable to vitamin D. Key advances in
      elucidation of the scope of vitamin D endocrine system include the tissue
      distribution of both its steroid receptor and its gene-induced product, a 28,000
      dalton calcium binding protein, termed calbindin-D28k. To date no less than 23
      tissues have been found to have specific 1,25(OH)2D3 receptors; of these at least
      10 were identified in avian studies. Similarly, nine avian tissues have been
      found to express the vitamin D-induced calcium binding protein, calbindin-D28k.
      These observations collectively demonstrate both the broad scope of the vitamin D
      endocrine system and the appropriateness of using avians as valid models for
      vitamin D endocrine research which has applicability and validity for mammals,
      including man.

PMID- 1974803
TI  - Phylogenetic approach to endocrine-immune system interactions.
AB  - The survival of organisms in a hostile and highly variable environment is
      dependent upon the proper balance of physiological processes. According to
      emerging views, homeostasis may be achieved by the coordinated activities of the
      three major integrative systems: the nervous, endocrine, and immune systems.
      Although each of these systems is replete with its particular molecules, cells,
      tissues, and organs, often not seemingly integrated into the whole organism,
      homeostasis is uncompromised and the three systems function properly. This mini
      review contains the essence of newer approaches which emphasize those which are
      being developed in our laboratory. Our model is concerned with the regulation of
      the immune system by the brain in fish.

PMID- 1974804
TI  - Nonmammalian vertebrate models in studies of brain-steroid interactions.
AB  - Estrogen formation in brain and pituitary mediates certain androgen actions in
      central targets. Goldfish (Carassius auratus) and quail (Coturnix coturnix
      japonica) have been advantageous for studying the role of locally formed estrogen
      in autoregulating aromatization and in controlling estrogen receptor occupancy,
      androgen receptor levels, and behavioral expression. Data from these two
      experimental models reveal a molecular basis for androgen-estrogen synergism in
      neuroendocrine tissues and for alterations in androgen
      sensitivity/responsiveness. These mechanisms are essential components of seasonal
      reproduction in the test species and may have wider relevance for cyclicity in
      other vertebrates, including mammals.

PMID- 1974805
TI  - Neuropeptide families: an evolutionary perspective.
AB  - Changes in the structure and function of five neuropeptide families during
      evolution are considered. The families of gonadotropin-releasing hormone (GnRH),
      corticotropin-releasing factor (CRF), growth hormone-releasing hormone (GH-RH),
      somatostatin (SS), and vasopressin/oxytocin (VP/Oxy) are used as models to
      illustrate the importance of a phylogenetic approach in understanding
      neuropeptide structure/activity relationships, precursors, processing, gene
      duplication, novel locations and functions, and gene-associated peptides.

PMID- 1974806
TI  - Pigeon crop-sac as a model system for studying the direct and indirect effects of
      hormones and growth factors on cell growth and differentiation in vivo.
AB  - The pigeon crop-sac is an underappreciated and underutilized model that can be
      used to study the direct and indirect effects of hormones, growth factors, and
      other agents on cell proliferation and differentiative processes in vivo. It can
      thus allow the uncertainties that attend many in vitro methods to be avoided. In
      addition, the crop mucosal cells are homogeneous and the organ is structurally
      much less complex than most other hormone-responsive target organs, such as the
      mammary gland or prostate. The organ is well suited for various other studies
      such as analysis of second-messenger systems for PRL and growth factors and the
      effects of growth-inhibitory substances.

PMID- 1974807
TI  - Xenopus laevis oocytes injected with mammalian pituitary mRNA as a model system
      for study of thyrotropin-releasing hormone action.

PMID- 1974808
TI  - Endocrine-nutrition interactions in birds.
AB  - This review will discuss the uses of avian models, particularly the chicken, to
      examine nutrition-endocrine interactions. The chicken has been employed
      extensively to examine nutritional effects. The effects of fasting, protein
      deficiency and calcium deficiency on endocrine status have been the subject of
      intense investigation in young chicks and adult female chickens. The ratio of
      circulating concentrations of triiodothyronine (T3) and thyroxine (T4) is
      substantially changed by fasting or protein deficiency. Similarly, protein
      deficiency reduces circulating concentrations of insulin-like growth factor I
      (IGFI) while protein deficiency increases growth hormone (GH). Moreover, protein
      deficiency increases the sensitivity and responsiveness of adrenocortical cells.
      The chicken also as advantages for studying diabetes, endocrine pancreatic
      functioning due to the splenic lobe of the pancreas being predominantly endocrine
      in nature, and the cellular mechanism of GH on chicken adipose tissue. The adult
      female chicken with its high calcium requirement is a unique system for examining
      nutritional effects on reproduction.

PMID- 1974809
TI  - P-glycoprotein and progesterone receptor in human breast cancer.

PMID- 1974810
TI  - The betrayal of homeo box genes in normal development: the link to cancer.
AB  - The homeo box genes encode proteins that function in a complex regulatory network
      that specifies the precise temporal and spatial expression of genes in the
      developing embryo. Recent work has shown that these proteins can act directly as
      transcription factors. I argue here that, when altered by somatic mutation, the
      products of homeo box genes are likely to acquire activities that contribute to
      the oncogenic process.

PMID- 1974812
TI  - Interim proposal for a WHO Staging System for HIV infection and Disease.

PMID- 1974811
TI  - Expanded programme on immunization. Global Advisory Group. Part I.

PMID- 1974813
TI  - Immunohistochemical detection of multidrug resistance associated P-glycoprotein
      in tumour and stromal cells of human cancers.
AB  - The distribution of Gp 170, a multidrug resistance (MDR) associated glycoprotein,
      also called P-glycoprotein (P-gp), was examined by immunohistochemistry, using
      C219 and MRK16 monoclonal antibodies. Sixty-five tumour tissues were studied
      which included 40 non-lymphoid tumours, 15 chemoresistant non-Hodgkin's lymphomas
      and 10 Hodgkin's disease. The study was performed on both cryostat and special
      fixation processed and paraplast embedded (ModAMeX) sections. The latter method
      preserves fixation-sensitive antigens such as P-gp and allows a more precise
      morphological identification of neoplastic and non-neoplastic cell populations in
      contrast to cryostat sections. Immunohistochemical expression of P-gp was
      expected and confirmed in many non-lymphoid tumours, but stromal macrophages and
      endothelial cells were also frequently stained in these cases. In non-Hodgkin's
      lymphomas, cells that were stained with both C219 and MRK16 monoclonal antibodies
      on cryostat sections were identified as macrophages and endothelial cells and not
      neoplastic lymphoid cells, by the ModAMeX technique. These findings suggest that
      the quantitative assessment of MDR RNA by Northern blotting performed on fresh
      homogenates overestimates the MDR content of neoplastic cells in a number of
      lymphoid and non-lymphoid tumours. In addition, the mechanism of chemoresistance
      in non-Hodgkin's lymphomas is less likely to be associated with P-gp expression.

PMID- 1974814
TI  - The effect of hyperthermia in combination with melphalan on drug-sensitive and
      drug-resistant CHO cells in vitro.
AB  - The effect of temperature on the cytotoxicity of melphalan in a pleiotropic drug
      resistant mutant CHO cell line (CHR C5) and in its drug-sensitive parent (Aux B1)
      was studied in vitro using a clonogenic assay. The cytotoxicity of melphalan was
      significantly enhanced at elevated but non-lethal temperatures (39-41 degrees C)
      and hyperthermia potentiated the effect of melphalan in the lethal temperature
      range (43-44 degrees C) in both cell lines. The effect of temperature on membrane
      permeability to melphalan was studied to determine whether the increase in
      cytotoxicity was associated with increased intracellular drug levels. The uptake
      of 14C-labelled melphalan during 5 min increased with increasing temperature.
      Drug efflux, however, also increased at elevated temperatures. Intracellular drug
      levels at equilibrium were increased at elevated temperatures but the magnitude
      of this effect was small in comparison with the much larger increases in
      cytotoxicity.

PMID- 1974815
TI  - Immunohistocytochemical correlation of DAP IV-CD 26 reactivity with immunologic
      markers of lymphocyte activation in human lymphoid tissues.
AB  - The topographic distribution of the dipeptidylaminopeptidase IV (DAP IV-CD 26)
      and II (DAP II) positive T-cell population in six reactive lymph nodes and seven
      follicular B-cell non-Hodgkin's lymphomas (NHL) was analysed with regard to the
      distribution of activated T-cells, as visualized by a panel of monoclonal
      antibodies including Tac-CD 25, HLA-DR, OKT 9-CD 71, ICAM-1-CD 54, LFA-1-CD 11a.
      For comparative studies serial frozen sections of the lymph nodes were tested by
      enzyme histochemistry and immunohistochemistry. In addition, cell suspensions
      obtained from 10 B-NHL and interleukin-2 (IL-2) activated T-cells were
      investigated by a combined cytochemical and immunological method for simultaneous
      visualization of DAP IV-CD 26 cytoplasmic activity and surface immunostaining for
      markers of lymphocyte activation. Both in reactive and lymphomatous lymph nodes
      the topographic distribution of DAP IV-CD 26+ and DAP II+ lymphocytes was rather
      similar to that of Tac-CD 25+ lymphocytes. On the contrary, the DAP IV-CD 26 and
      DAP II distribution pattern substantially differed from that of the other
      immunologic markers. In a cell suspension of IL-2 activated T-cells, more than
      80% of the cells with a blastic morphology were DAP IV-CD 26+; DAP IV-CD 26+
      cells coexpressing Tac-CD 25, OKT 9-CD 71, HLA-DR positivity, relative to the
      total number of DAP IV-CD 26 positive cells, were 90.5%, 70.5% and 87%
      respectively. Only small (not activated) lymphocytes expressed a focal
      cytoplasmic DAP II positivity. In cell suspensions from 10 cases of B-NHL the
      mean percentage of DAP IV-CD 26+ Tac-CD 25+ cells was 75.8. Only a small number
      of DAP IV-CD 26+ cells coexpressed HLA-DR, the mean percentage being 9.6. The
      results support the view that DAP IV-CD 26 may be considered as a marker of
      lymphocyte activation; this marker seems to be restricted to T lymphocytes that
      reside in the T dependent areas of reactive lymph nodes and to non malignant T
      cells surrounding neoplastic follicles of follicular NHL.

PMID- 1974816
TI  - The human CYP2F gene subfamily: identification of a cDNA encoding a new
      cytochrome P450, cDNA-directed expression, and chromosome mapping.
AB  - A cDNA coding for a P450, designated IIF1, was isolated from a human lung lambda
      gt11 library by screening with a human IIC9 cDNA probe. The cDNA-encoded IIF1
      protein had 491 amino acids and a calculated molecular weight of 55,507. IIF1
      cDNA, expressed by using a vaccinia virus vector, produced a cytochrome with a
      lambda max of 454 nm when reduced and complexed with carbon monoxide. This enzyme
      was able to dealkylate ethoxycoumarin, propoxycoumarin, and pentoxyresorufin but
      possessed no activity toward ethoxyresorufin and only trace dearylation activity
      toward benzyloxyresorufin. A variant cDNA, designated IIF1v, was isolated that
      was identical with IIF1 except for the loss of two segments of 161 and 388 bp
      within the cDNA coding region. Two mRNAs, consistent with the predicted size of
      the IIF1 and IIF1v transcripts, were found at very low abundance in lung
      specimens by Northern blot analysis. A 2-kb transcript, hybridizing with the
      human IIF1, was also detected as an abundant mRNA in rat lung. The CYP2F gene
      subfamily was localized to human chromosome 19 and mouse chromosome 7. On the
      basis of Southern blotting analysis with multiple restriction enzymes, we
      conclude that the CYP2F1 gene is flanked by a second highly similar gene.

PMID- 1974817
TI  - [Effect of tuftsin and hydroxymethacil on tyrosine hydrolase of macrophages in
      chronic stress].
AB  - It has been established that rat peritoneal macrophages possess tyrosine
      hydroxylase activity which has been characterized by KM4, 2 microM, Vmax 30
      nmole/min per mg of protein. After 15 days of electronociseptive stimulation
      almost all tyrosine hydroxylase activity has been established in the form which
      has tyrosine KM47.0 M and Vmax 18.6 nmole/min. per mg of protein.
      Immunostimulator hydroxymethacil++, at its intraperitoneal injections to stressed
      rats during 7 days induced the appearance of low-affinity form of tyrosine
      hydroxylase with KM270 microM and Vmax 27.8 nmole/min.per mg of protein. The same
      low affinity form of the enzyme has been established after injections of tuftsin
      which possesses immunostimulating properties.

PMID- 1974818
TI  - [Immunostimulating effect of D2 dopamine receptor agonist quinpirole].
AB  - Immunostimulating activity of specific postsynaptic D2 receptor agonist
      quinpirole (Ly 171555) was studied in CBA mice. The drug was administered
      intraperitoneally in a dose of 1 mg/kg 30 min before the immunization with SRBC
      (5 x 10(8)). Considerable stimulation of rosette- and plaque-forming cell number
      was observed at the early stage (3-d day) and at more late stage of the immune
      response (5-th day). The increase of rosette- and plaque-forming cell number was
      provided by IgM-reaction enhancement.

PMID- 1974819
TI  - Mental precursors of myocardial infarction.
AB  - Both cardiologists and psychiatrists have observed that the onset of myocardial
      infarction is often preceded by feelings of decreasing energy, general malaise,
      and minor depression. This paper describes these observations and tries to
      integrate the findings. It is proposed that the mental state preceding myocardial
      infarction can be best described as 'vital exhaustion'.

PMID- 1974820
TI  - Frequency of and determinants for psychotropic drug use in an institution for the
      mentally retarded.
AB  - The frequency of psychotropic and anticonvulsant drug use in 168
      institutionalised mentally retarded adults was studied. Use of neuroleptics and
      anticonvulsants was more frequent and use of hypnotics and antidepressants less
      frequent than in the general population. Neuroleptics were given to 49% of the
      population. Clients with no psychiatric diagnosis consumed less neuroleptics than
      those with such a diagnosis, and there was a non-significant trend for those with
      a more serious diagnosis (e.g. schizophrenia) to take a higher dosage. The degree
      of disruptive behaviour and the availability of a physician were related to
      dosage of neuroleptics. The various psychiatric diagnoses given could explain
      only a small proportion of the variance in dosage.

PMID- 1974821
TI  - Expression of the multidrug transporter, P-glycoprotein, in acute leukemia cells
      and correlation to clinical drug resistance.
AB  - The overexpression of a cell-surface glycoprotein termed P-glycoprotein (P-gp) is
      frequently associated with multi-drug resistance (MDR) in cell lines in vitro. To
      evaluate the implications of P-gp expression in clinical drug resistance, the
      authors examined the expression of P-gp in leukemia cells from patients with
      acute myelogenous leukemia (AML) and those with acute lymphoblastic leukemia
      (ALL) at initial presentation and relapse, using immunoblotting with a monoclonal
      antibody against P-gp, C219. Nine of 17 patients with AML and four of 11 patients
      with ALL had P-gp-positive results at the initial presentation, and most P-gp
      positive patients did not respond to chemotherapy. Four of seven patients at the
      relapsed stage and all three patients with preceding myelodysplastic syndrome had
      P-gp-positive results. The expression of P-gp and clinical refractoriness to
      chemotherapy were highly correlated. These data indicate that the expression of P
      gp is closely related to clinical drug resistance in acute leukemia.

PMID- 1974822
TI  - Failure of chronic glutathione elevation to reduce cytotoxicity produced by
      exposure to cis-diamminedichloroplatinum(II), ionizing radiation, or
      hyperthermia.
AB  - Chinese hamster ovary (CHO) cells cultured in vitro were continuously exposed to
      increasing concentrations of diethylmaleate (DEM). Chronic exposure of these
      cells (designated CHO/DEM) to 80 microM diethylmaleate resulted in an increase in
      cystine transport, a decrease in glutathione inhibition of the enzyme gamma
      glutamylcysteine synthetase, elevation of intracellular glutathione levels to 4.3
      times control, and elevation of glutathione-S-transferase activity by 6.6 times.
      Yet, CHO/DEM and control CHO cells exhibited the same ability to synthesize
      protein as measured by two-dimensional electrophoresis, the same cell cycle
      distribution, and the same population doubling times. CHO/DEM cells are resistant
      to DEM and diamide cytotoxicity, compared to control CHO cells. CHO/DEM cells
      were used to address the question of whether chronic elevation of glutathione,
      above control concentrations, reduced the cytotoxicity produced by exposure to
      cisplatin, gamma-radiation, or hyperthermia. The resulting dose-response curves
      obtained with CHO/DEM and control CHO cells indicated that chronic exposure to
      DEM, which resulted in chronic elevation of glutathione, did not provide
      protection against any of the three toxic treatments.

PMID- 1974823
TI  - Non-P-glycoprotein mediated mechanism for multidrug resistance precedes P
      glycoprotein expression during in vitro selection for doxorubicin resistance in a
      human lung cancer cell line.
AB  - Two different mechanisms that contribute to multidrug resistance (MDR) were found
      in derivatives of the human squamous lung cancer cell line SW-1573. The parental
      cell line has a low amount of mdr1 P-glycoprotein mRNA. In three independent
      selections for doxorubicin resistance, MDR variants arose in which mdr1 P
      glycoprotein mRNA and protein was not detectable. Selection on higher doxorubicin
      concentrations gave rise to variants containing high levels of mdr1 mRNA, due to
      transcriptional activation of the mdr1 gene. Upon continued selection for higher
      levels of doxorubicin resistance, the mdr1 gene became amplified, resulting in an
      additional increase in the level of mdr1 mRNA. The cross-resistance pattern of
      the sublines that lack mdr1 P-glycoprotein expression is different from that seen
      in the mdr1 overexpressing cells. Both types of MDR cell lines are resistant to
      doxorubicin, daunorubicin, etoposide, colchicine, gramicidin D, and vincristine.
      However, in the non-P-glycoprotein-mediated MDR cell lines, resistance levels are
      lower and a preferential resistance for etoposide is seen.

PMID- 1974824
TI  - Immunopathogenesis of human immunodeficiency virus infection.
AB  - The acquired immunodeficiency syndrome (AIDS) is associated with a broad spectrum
      of opportunistic infections and neoplasias that differ from those occurring in
      the general population by their high aggressiveness, unusual location, early
      tendency to generalization, frequent relapse, and short survival. The severe
      complications of AIDS, however, represent only the last phase in a prolonged
      course of progressive dysfunction and destruction of the immune system set in
      motion by the infection with the human immunodeficiency virus (HIV). While
      substantial progress was achieved in the ultrastructural identification and
      biochemical characterization of HIV, its mode of action in the causation of AIDS
      is not yet fully understood. This article explores the main processes involved in
      the HIV infection and in its role in the origin of AIDS. It describes the phases
      of HIV infection, investigates the effects of HIV on the various components of
      the immune system, and analyzes the pathogenesis of the HIV-induced
      lymphadenopathies and encephalopathy, as well as the causes and mechanisms of
      AIDS-associated opportunistic infections and opportunistic neoplasias. The total
      failure of immune surveillance against a host of infectious and oncogenic agents,
      unprecedented in human pathology, is thus traced to the initial event of specific
      HIV infection of the CD4 T-lymphocytes.

PMID- 1974825
TI  - Changes in the level of soluble CD-2 molecules in the serum of HIV-infected
      individuals.
AB  - It has been shown previously that the level of soluble CD-2 determinants (E
      receptors) is elevated in the serum of patients with various immunodeficiency
      states. The aim of the present preliminary study was to determine the level of
      soluble CD-2 in the sera of individuals infected with human immunodeficiency
      virus (HIV), in order to assess the contribution of soluble CD-2 molecules to the
      immunological deterioration of these patients. The serum CD-2 concentration was
      determined by an enzyme-linked immunosorbent assay, using a monoclonal CD-2
      antibody. Considerable levels of CD-2 were detected in the sera of 15.9% of 63
      normal controls tested, with a mean absorbance at 492 nm of 0.154 +/- 0.033. In
      contrast, in none of the 13 asymptomatic HIV-infected individuals tested could
      soluble CD-2 be detected (mean absorbance of 0.00093 +/- 0.0048). Elevated
      concentrations of CD-2 were found in the sera of 3 of 12 patients tested who were
      suffering from acquired immunodeficiency syndrome (AIDS). Thus, following HIV
      infection there is an initial phase of reduction of soluble CD-2, probably
      reflecting diminished T-cell activation. Thereafter, in some AIDS patients
      episodes of T-cell destruction seem to be correlated with the release of CD-2
      molecules into the serum.

PMID- 1974826
TI  - Immunosuppression in murine renal cell carcinoma. II. Identification of
      responsible lymphoid cell phenotypes and examination of elimination of
      suppression.
AB  - In our companion paper we have reported that cell-mediated immunity of mice
      bearing renal cell carcinoma is profoundly suppressed. The non-responsiveness of
      such animals was found to be attributable to Renca cells themselves and to
      splenic lymphoid cells that down-regulate other fully capable lymphoid cells. In
      this communication the lymphoid cell source of suppression within Renca-bearing
      mice has been explored with the aim of identifying phenotypes of the responsible
      cells, the manner by which suppression is mediated, and initial ways by which
      suppression may be eliminated. A plastic-adherent cell bearing the Thy1.2 surface
      marker as well as the Lyt1 and Lyt2 antigens has been found to operate, perhaps
      in conjunction with macrophages, to down-regulate lymphokine-activated killer
      (LAK) cell development for natural killer (NK) and non-NK targets that include
      Renca cells themselves. The splenic suppressor cells lost the capacity to
      suppress the NK response of normal recipient mice upon shallow irradiation (250
      rad) prior to adoptive transfer. Spleen cells, presumably macrophages, from Renca
      bearing mice were found to suppress the generation of LAK and NK cells in vitro
      by synthesizing prostaglandins. Indomethacin, a prostaglandin synthetase
      inhibitor, blocked the induction of suppression both in vitro and in vivo,
      suggesting the presence of endogenous prostaglandins in Renca-bearing mice. The
      suppression seen in Renca-bearing mice that derives from multiple sources and has
      been prevented by two separate methods has been discussed from the viewpoint of
      the inter-relatedness of the sources.

PMID- 1974827
TI  - Intravenous digital subtraction angiography in patients with aorto-arteritis
      (Takayasu's).
AB  - Aorto-arteritis is one of the commonest vascular diseases in China as well as in
      Japan and other parts of Asia. The results of digital subtraction angiography
      (DSA) in 50 patients with aorto-arteritis are reported, and the merits and
      demerits of intravenous (IV) DSA in the diagnosis of this entity are evaluated.
      Among the 51 studies performed on 50 patients, IV DSA was used in 48,
      intraarterial (IA) DSA in 3, and good-to-excellent visualization was obtained in
      96% of patients. Aorto-arteritis of varying severity and involving the thoraco
      abdominal aorta, the iliac arteries, and other major branches was clearly
      demonstrated by IV DSA. IV DSA, as compared to our previous experience with
      conventional arteriography in this entity, may be substituted for conventional
      arteriography in most patients. A large dose of contrast media needed for a
      complete study is a major deficiency of IV DSA, and it also has limitations for
      showing the intrarenal arterial branches.

PMID- 1974828
TI  - Poxviruses: an emerging portrait of biological strategy.
AB  - The meeting offered ample evidence that the field of poxvirology has truly come
      of age. Many investigators were attracted to the field by its experimental
      feasibility; indeed, the virions are "in vitro transcription systems" and the
      genome is a "cDNA library." The viral life cycle is synchronous and rapid and can
      be studied genetically and biochemically in a wide range of cell types. What has
      become clear is that the virus also offers a unique opportunity to dissect a
      range of biological problems. The enzymes involved in nucleic acid metabolism are
      numerous and easily accessible to study; vaccinia is fast evolving into a model
      system of choice for structure-function studies. The cascade of gene expression
      offers a chance to investigate in detail the mechanism of trans-acting factors
      that determine transcriptional specificity, as well as a system to probe the role
      of genome "chromatin" in dictating the accessibility of transcriptional units.
      But perhaps the most lasting impression of vaccinia is as a virus that encodes a
      unique repertoire of proteins governing its survival within the host. Among these
      are proteins that may activate the next round of cells to be infected, reduce the
      activation of cells responsible for the inflammatory response, and sabotage the
      biochemical cascades of host defenses. Never before has a virus held up a mirror
      so intriguing and so informative.

PMID- 1974829
TI  - Enhanced preneoplastic liver lesion development under 'selection pressure'
      conditions after administration of deoxycholic or lithocholic acid in the
      initiation phase in rats.
AB  - The initiating potential of the secondary bile acids, deoxycholic acid (DCA) and
      lithocholic acid (LCA), for rat hepatocarcinogenesis was investigated using the
      development of hyperplastic nodules and/or glutathione S-transferase placental
      form (GST-P)-positive liver foci as the end point. Five week old male F344 rats
      were given either basal diet, or diets containing 0.5% DCA or 0.5% LCA for 3
      weeks in conjunction with partial hepatectomy performed midway, followed by a
      selection regimen consisting of 2 weeks feeding of 0.02% 2-acetylaminofluorene
      diet and a single gastric intubation of carbon tetrachloride. The animals were
      then placed on either basal diet or a diet containing 0.05% phenobarbital (PB)
      for 52 weeks. Significantly higher numbers of hyperplastic liver nodules
      developed in the DCA-treated rats irrespective of PB promotion as compared with
      the respective control groups. No such increase was evident in the LCA-treated
      rats. In contrast, both DCA and LCA treatments enhanced the development of GST-P
      positive liver foci with or without subsequent PB promotion. Only one
      hepatocellular carcinoma was diagnosed in a control group animal. The present
      data indicate that a short period of feeding of DCA and LCA in the initiation
      stage in conjunction with partial hepatectomy results in enhanced development of
      preneoplastic liver lesions under selection pressure conditions with or without
      subsequent PB promotion. They thus confirm and extend our previous finding of
      enhanced gamma-glutamyltranspeptidase-positive liver foci development in a short
      term assay of DCA and LCA, and suggest that these secondary bile acids either
      possess possible initiating activity or some other priming effect for rat
      hepatocarcinogenesis.

PMID- 1974830
TI  - Deamidation of glutamine by increased plasma gamma-glutamyltransferase is a
      source of rapid ammonia formation in blood and plasma specimens.
AB  - Owing to increased enzymatic hydrolysis of glutamine, additional ammonia is
      formed in blood and plasma specimens with increased gamma-glutamyltransferase
      activity (gamma-GT, EC 2.3.2.2.). The close correlation between gamma-GT and
      glutaminase (EC 3.5.1.2) activities (r = 0.97) in plasma, the inhibition with 6
      diazo-5-oxo-L-norleucin or borate plus serine, and the activation with maleate
      clearly show that gamma-GT itself is the glutamine-deamidating enzyme in plasma.
      Under pathological conditions, increased gamma-GT activity can increase the rate
      of ammonia formation in plasma more than 30-fold the mean values of healthy
      subjects. Increased in vitro formation of ammonia caused by increased gamma-GT
      activity is an important source of false-positive findings in ammonia
      determination. Because of the high prevalence of pathological gamma-GT activities
      in clinical populations, blood specimens for ammonia analysis should be preserved
      by addition of borate plus serine.

PMID- 1974832
TI  - [Spatial distribution of the peripheral nerve lesion in polyarteritis nodosa].
AB  - We have examined the peripheral nerves in four patients with polyarteritis
      nodosa. They were consisted of two males and two females with the age of 70, 49,
      65 and 75 years respectively. The sciatic and posterior-tibial nerves, sural
      nerves, ventral and dorsal spinal nerve roots, dorsal ganglia and spinal cord
      were removed at autopsy. Particularly, the sciatic and posterior-tibial nerves
      were removed as a whole and suspended in a glass cylinder with a weight and fixed
      in 1.5% glutaraldehyde and 0.05 M phosphate buffer, pH 7.4 for 16 hours. The
      nerve fragments of every 3 to 3.5 cm along the sciatic and posterior-tibial nerve
      were examined on conventional paraffin-embedded and epon-embedded sections, and
      osmicated teased-fibers. Necrotizing angitis was commonly present in the
      epineurium of the sciatic and posterior-tibial nerves in all four patients.
      Although necrotizing angitis was diffusely distributed in the proximal to distal
      portions of the nerve, loss of myelinated fibers, occurred only in the distal to
      mid-lower portions of the sciatic nerve. There was no substantial myelinated
      fiber loss in the proximal part of the sciatic nerve in three of four cases.
      Myelinated fiber loss in the fascicle was central fascicular or multiple-focal in
      pattern in the proximal portions of the nerve, but was diffuse in more distal
      portion of the posterior tibial nerve. Segmental demyelination and myelin
      irregularity in the teased-fiber preparation were more prominently observed in
      the proximal portions, but fibers with axonal degeneration were more frequent in
      the distal portions of the nerve.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1974831
TI  - The development of primed/memory CD8+ lymphocytes in vitro and in rejecting
      kidneys after transplantation.
AB  - In normal individuals, 80 +/- 5% of circulating CD8+ T cells express CD45RA, and
      20 +/- 7% of these cells express CD45R0 antigens. After activation, CD8+ cells
      expressing CD45RA decrease to 56-67% while those expressing CD45R0 increase to 38
      67%. Although precursors of alloantigen-specific cytotoxic T cells were found in
      both CD8+, CD45RA+ and CD8+, CD45R0+ subsets, the specific effector cells were
      exclusively CD8+, CD45R0. Allospecific cytotoxic CD8+ clones were also entirely
      CD45R0+. A lectin-dependent cytotoxic (LDC) assay unmasked a hierarchy of killing
      after alloactivation which was CD8+, CD45R0+ greater than CD8+, CD45RA+ greater
      than CD4+, CD45R0+ greater than CD4+, CD45RA+. The phenotype of CD8+ T cells in
      rejecting kidneys was similar to in vitro alloantigen-activated CD8+, CD45R0+
      cells and cytotoxic CD8+ clones. Firstly there was an increase in the relative
      proportions of CD45R0+ (60 +/- 8%) and a decrease in CD45RA+ (35 +/- 10%) CD8+
      cells relative to circulating CD8+ subsets. In the rejecting grafts, 34 +/- 9% of
      the CD8+ cells were also DR+ indicative of recent activation. Furthermore, 16%
      (range 4-35%) of rejecting CD8+ cells were Ki67+ suggesting that these cells were
      proliferating. Finally, 17% (range 4-53%) of T cells in rejecting kidneys
      simultaneously expressed both CD45RA and CD45R0 markers. These results show that
      in vitro alloantigen-activated CD8+, CD45R0+ cells represent a primed/memory
      cytotoxic population. In addition, they provide indirect evidence that a
      proportion of CD8+ cells in rejecting kidneys were actively switching from a
      naive to a memory phenotype in vivo in a manner analogous to that in vitro.

PMID- 1974833
TI  - Clinical implications of positive tests for antibodies to human immunodeficiency
      virus type 1 in asymptomatic blood donors.

PMID- 1974835
TI  - The reservoir for HIV-1 in human peripheral blood is a T cell that maintains
      expression of CD4.

PMID- 1974834
TI  - Lack of association between DQ A and DX A polymorphisms with rheumatoid arthritis
      and Felty's syndrome.
AB  - DQ A and DX A RFLPs were studied in DR4-positive rheumatoid arthritis, Felty's
      syndrome, and in DR4-positive control subjects, and in the light of the
      previously documented association between Felty's syndrome and the DQ B 3.1
      allele (3b RFLP). In these DR4-positive subjects there were no preferential
      associations between DQ A or DX A polymorphisms and rheumatoid arthritis or
      Felty's syndrome and no evidence for unusual DQ A-B haplotypic associations in
      Felty's or rheumatoid subjects.

PMID- 1974836
TI  - Attention-deficit hyperactivity disorder.
AB  - The epidemiology, etiology, pathogenesis, clinical presentation, diagnostic
      criteria, and clinical course of attention-deficit hyperactivity disorder (ADHD)
      are described and the role of pharmacotherapy in the management of this disorder
      is discussed. ADHD is a behavioral disorder of unknown etiology characterized by
      inattention, impulsiveness, and hyperactivity. The behavior, which may be
      manifest at home, at school, or in social situations, is generally worse in
      settings requiring sustained attention; as a result, academic underachievement is
      frequently an associated problem. Although the onset usually occurs before the
      age of four years, ADHD is most commonly diagnosed when the child enters school.
      It is up to six times more common in boys than in girls. Nearly one third of all
      children with ADHD continue to show symptoms of the disorder in adulthood. While
      many questions about the pathophysiology of ADHD remain unanswered and a cure has
      not yet been found, pharmacotherapy can effectively control the symptoms of the
      disorder in most patients. Three psychostimulant medications--dextroamphetamine
      sulfate, methylphenidate hydrochloride, and pemoline--are considered the drugs of
      first choice for management of the behavioral manifestations of ADHD.
      Dextroamphetamine and methylphenidate are equally effective in improving the
      symptoms of ADHD. Pemoline, a newer agent, may be tried in patients who cannot
      tolerate or do not respond to these two first-line agents. Common adverse effects
      associated with stimulant medications include anorexia, insomnia, stomach pain,
      and weight loss; these are generally transient and decrease with time. Imipramine
      hydrochloride and desipramine hydrochloride are less effective and may produce
      more serious adverse effects than the psychostimulants and are therefore
      considered second-line agents for the treatment of ADHD. Dextroamphetamine
      sulfate, methylphenidate hydrochloride, and pemoline have been shown to
      effectively control the behavioral symptoms of ADHD. For maximum impact,
      pharmacotherapy should be accompanied by behavioral, educational, and
      psychosocial intervention.

PMID- 1974837
TI  - Beta-adrenergic receptors: structure, function and regulation.
AB  - The diverse effects of the catecholamines (CA) epinephine and norepinephrine are
      mediated by a family of specific receptors (adrenergic receptors, AR). The beta
      AR is a glycoprotein present in the membrane of a number of cell types. This
      receptor is closely associated with at least two other proteins (Gs and adenylate
      cyclase enzyme, AC) to form the beta-AR complex. The beta-AR recognizes the CA
      and is coupled to Gs which stimulates the effector enzyme AC. This enzyme
      converts ATP to cAMP and is the effector of the beta-AR complex. Thus the beta-AR
      is a G-coupled receptor which acts by raising intracellular levels of cAMP. The
      beta-AR is an important site of regulatory modifications through a variety of
      mechanisms. The best characterized is known as homologous desensitization: when
      the receptor is exposed to repeated stimulus by the agonist (CA), its
      responsiveness wanes, probably to compensate this potentially dangerous
      overstimulation. The gene for mammalian beta2-AR has been recently cloned and the
      predicted amino-acid sequence now opens the field to identification of the
      protein structures involved in receptor functions. The beta2-AR protein is
      characterized by the presence of seven membrane spanning regions. Study of the
      structure, function and regulation of the beta-AR will extend our knowledge of
      the role of beta-AR in pathological conditions and suggest new therapeutic
      approaches.

PMID- 1974838
TI  - Beta-blockers and primary cardioprotection in hypertension.
AB  - Theoretical and experimental data coupled with findings from several studies,
      showing the beneficial effect of beta-blocking therapy in reducing the risk of
      death and re-infarction among infarct patients (secondary cardioprotection),
      suggested that beta-blockers could reduce the incidence of coronary events also
      in hypertensive patients with no clinical evidence of coronary heart disease
      (CHD) (primary cardioprotection). In order to evaluate the primary
      cardioprotective potential of beta-blockers as compared to diuretics in the
      treatment of hypertension, some large-scale, randomized, prospective studies were
      set up in the middle and late 1970s. The results of three of these trials, the
      MRC, the IPPPSH and the HAPPHY studies, were negative or non-conclusive and
      somehow conflicting. None of them showed any difference between beta-blockers and
      diuretics in reducing the incidence of CHD, but the MRC and the IPPPSH studies
      suggested that beta-blockers were better than diuretics in male non-smokers.
      However, the HAPPHY study did not confirm such a hypothesis. More recently, two
      studies, the Clatterbridge study (retrospective, non-controlled) and the MAPHY
      study (prospective, controlled) gave positive results about the primary
      cardioprotective effect of beta-blockers. In particular, the MAPHY study
      demonstrated that starting antihypertensive treatment with the beta1-selective
      beta-blocker metoprolol instead of a thiazide diuretic led to lower total and
      cardiovascular mortality, mainly by reducing fatal CHD and fatal stroke. Although
      more evidence is needed, the primary cardioprotective effect demonstrated with
      metoprolol in the MAPHY study might have important implications for clinical
      practice and public health.

PMID- 1974839
TI  - Cardioprotection by beta-blockers: molecular and structural aspects in
      experimental hypertension.
AB  - This paper deals with some changes at the cardiac and aortic levels observed in
      normotensive rats and in hypertensive rats and turkeys by using two different
      beta-blockers, namely propranolol and oxprenolol. Chronic treatment with
      propranolol induced in the heart of normotensive rats a shift in the ventricular
      myosin pattern toward the "slow" V2 and V3 isoforms which are characterized by a
      reduced oxygen consumption. Oxprenolol treatment did not modify the blood
      pressure levels in the renal hypertensive rats nor in the spontaneously
      hypertensive turkeys. Nevertheless, in both experimental models a substantial
      modification of the media and intima, respectively, took place. In untreated
      hypertensive and normal rats the thickness of the aortic media was significantly
      higher than that of the treated ones, therefore suggesting a direct effect of
      oxprenolol on the smooth muscle cells of the aortic media. In the spontaneously
      hypertensive turkeys the atherosclerotic plaques appeared to be more frequent and
      thicker than those found in the oxprenolol-treated animals. These two experiments
      demonstrate that beta-blockers can prevent the development of hypertrophy of the
      media and decrease both the incidence and severity of intimal proliferations
      independently of blood pressure control. It therefore appears that the well-known
      myocardial protective effect played by beta-blockers, which mainly consists of a
      reduced myocardial oxygen consumption, is certainly obtained by reducing blood
      pressure and heart rate but also by changing the contractile protein pattern. In
      addition, an indirect myocardial protective effect could be exerted by beta
      blockers at the vascular level by preventing medial hypertrophy and the
      development of atherosclerosis.

PMID- 1974840
TI  - Primary protection with beta-blockers in the treatment of hypertension.
AB  - The treatment of hypertension has been associated with a reduction of stroke by
      nearly a half but with little or no effect on the incidence of heart attack.
      Hypotheses to account for this discrepancy include the short duration of the
      trials, the differential effects on initial subsets according to age, sex and
      smoking status, the adverse effects of antihypertensive agents, the excessive
      lowering hypothesis and the common causal link hypothesis. Each of these
      hypotheses is examined in this paper.

PMID- 1974841
TI  - Neural expression of the Xenopus homeobox gene Xhox3: evidence for a patterning
      neural signal that spreads through the ectoderm.
AB  - The Xenopus laevis homeobox gene Xhox3 is expressed in the axial mesoderm of
      gastrula and neurula stage embryos. By the late neurula-early tailbud stage,
      mesodermal expression is no longer detectable and expression appears in the
      growing tailbud and in neural tissue. In situ hybridization analysis of the
      expression of Xhox3 in neural tissue shows that it is restricted within the
      neural tube and the cranial neural crest during the tailbud-early tadpole stages.
      In late tadpole stages, Xhox3 is only expressed in the mid/hindbrain area and can
      therefore be considered a marker of anterior neural development. To investigate
      the mechanism responsible for the anterior-posterior (A-P) regionalization of the
      neural tissue, the expression of Xhox3 has been analysed in total exogastrula. In
      situ hybridization analyses of exogastrulated embryos show that Xhox3 is
      expressed in the apical ectoderm of total exogastrulae, a region that develops in
      the absence of anterior axial mesoderm. The results provide further support for
      the existence of a neuralizing signal, which originates from the organizer region
      and spreads through the ectoderm. Moreover, the data suggest that this neural
      signal also has a role in A-P patterning the neural ectoderm.

PMID- 1974842
TI  - [The mesencephalic dopaminergic system. Implications for neuroleptic treatment].
AB  - Thirty years ago, dopamine was identified as an essential neurotransmittor. Since
      then, it has been the most written about CNS molecule. Considerable evidence
      implicates disturbances of brain dopamine function in the pathophysiology of
      several psychiatric and neurologic disorders, especially schizophrenia and
      Parkinson's disease. In the last decade, there have been important advances in
      the understanding of the diversity of CNS dopamine neurons and the chemical basis
      of this diversity, which relies upon molecular physiology of D1 and D2 receptors.
      Heterogeneity is remarkable at different levels, anatomical, biochemical,
      morphological or functional; besides, region specific interactions with other
      neurotransmittors and sometimes colocalisation of dopamine with cholecystokinin
      and/or neurotensin suggest the integration of dopamine neurons in functional
      subunits.

PMID- 1974843
TI  - [A new therapeutic approach: the behavioral prescription of anxiolytics].
AB  - Nowadays, two major therapeutic approaches (pharmacological and behavioural) have
      proven their efficiency and efficacy in the treatment of anxious disorders. These
      two methods have been used separately, alternatively or simultaneously. The
      prescription of benzodiazepines is necessary, because they are efficient and fast
      acting. But this is not enough and may be hazardous for a prolonged period.
      Behavioural methodology and therapeutics improve the assessment of anxious
      disorders and offer a large variety of specific techniques to the physician. The
      innovative and integrative behavioural prescription (BP) is pragmatic and
      reliable. For instance, drugs are markers for assessment of anxious behaviours,
      in an agenda and may be used both to support functional analysis, and as agents
      of therapeutic contracts. The synergic action of behavioural prescription is
      clear in three dimensions: BP deepens muscle relaxation and gives better self
      control and self-regulation of arousal level. BP alleviates social inhibition by
      developing social skills. BP modifies cognitions and affective disorders, which
      is necessary for permanent results and drug withdrawal. Other applications of BP
      will be considered in the future.

PMID- 1974844
TI  - [Psychopharmacologic profile of an aqueous extract of Piper umbellatum].
AB  - Piper umbellatum is a plant currently utilized in traditional medicine as a
      sedative. Administered to rats by intraperitoneal injection, an aqueous extract
      of this plant brings about an ataxia with a decrease in the animal's watchfulness
      which lasts about 48 hours. Are also concomitant to this decrease in
      watchfulness, a fall of the rectal temperature, a decrease of spontaneous motor
      activity as well as an increase of analgesic activity.

PMID- 1974845
TI  - Growth hormone and prolactin secretion in cultured somatomammotroph cells.
AB  - A somatomammotropic cell line (P0) derived from adult rat pituitaries has been
      maintained in culture for 2 yr. Secretion of GH and PRL by this cell line has
      been studied in response to hypophysiotropic peptides known to affect the release
      of both hormones as well as agents that affect second messenger systems in an
      attempt to characterize the stimulus-secretion mechanisms used by these cells. GH
      and PRL release during short term (4 h) incubations of P0 cells and primary
      cultures of dispersed rat pituitary cells was initially measured in response to
      GRF, TRH, vasoactive intestinal peptide (VIP), and SRIF. In P0 cells, the minimal
      effective dose of each of the hypophysiotropic peptides was comparable with
      respect to GH and PRL secretion. The effects of TRH and VIP were similar to those
      in freshly dispersed cells with respect to PRL release, whereas those of GRF and
      SRIF were less potent with respect to GH release. The stimulation of GH and PRL
      release in P0 cells by adenylate cyclase-related agents ((Bu)2 cAMP and
      forskolin) was comparable to that for GH secretion in mature somatotrophs but
      much greater than that of PRL release in mature lactotrophs. Stimulation of GH
      and PRL release in P0 cells by protein kinase C-related agents (diacylglycerol
      and phorbol ester) was also similar to that observed for GH release from mature
      pituitary cells, whereas minimal or undetectable effects were observed on PRL
      release from mature cells. The results indicate that the P0 somatomammotropic
      cell line possesses receptors, second messenger systems, and secretory
      characteristics of both somatotrophs and lactotrophs, although where differences
      exist, there is more resemblance to somatotrophs. They also demonstrate that the
      responses to each of the agents studied are bihormonal and appear to be regulated
      by a common mechanism.

PMID- 1974846
TI  - Photoperiodic control of adipocyte alpha 2-adrenoceptors in Syrian hamsters: role
      of testosterone.
AB  - The impact of photoperiodic manipulations and testosterone treatments on the
      adipocyte alpha 2-adrenergic (alpha 2-AR), beta-adrenergic (beta-AR), and A1
      adenosine (A1-R) responsiveness, was explored in male Syrian hamsters
      (Mesocricetus auratus). Moreover, binding studies were performed with appropriate
      alpha 2-AR, beta-AR, and A1-R radioligands to study receptor changes. Animals
      were kept for 12 weeks in long day photoperiod (LD: 16 h light (L)-8 h dark (D)),
      in short day photoperiod (SD: 6L-18D), or in short photoperiod with testosterone
      treatments (1 mg/animal/day sc) 10 days before sacrifice (SD+T). The
      antilipolytic effect of the full alpha 2-AR agonist UK14304 and the specific
      binding of the alpha 2-AR radioligands [3H] RX821002 (antagonist) and [3H]UK14304
      were significantly reduced in SD hamsters compared with LD hamsters. The alpha 2
      site number and alpha 2-AR responsiveness were completely restored in SD+T
      hamsters. Whatever the experimental conditions the adipocyte beta-AR receptivity
      (lipolytic response of isoproterenol and [125I]cyanopindolol binding), and the A1
      R receptivity (antilipolytic response initiated by (-)phenylisopropyladenosine
      and [3H]dipropyl-8-cyclopentylxanthine and [3H]phenylisopropyladenosine binding)
      remained unchanged. Moreover, the kidney and brain alpha 2-AR densities
      identified with [3H]RX821002 were not significantly different in LD, SD or SD+T
      hamsters. These results were obtained without any modification of animal weight,
      white adipose tissue weight, or white fat cell size. We conclude that, in the
      Syrian hamster, the expression of the adipocyte alpha 2-AR is under the control
      of the photoperiod by a testosterone-dependent mechanism probably mediated
      through the hypothalamic-pituitary axis, without any alteration of the animal fat
      stores.

PMID- 1974847
TI  - Effect of APV and ketamine on epileptiform activity in the CA1 and CA3 regions of
      the hippocampus.
AB  - Intracellular recordings were obtained from hippocampal CA1 and CA3 pyramidal
      neurons maintained in vitro. The ability of the NMDA receptor antagonists
      ketamine and APV to suppress picrotoxin-induced epileptiform burst activity was
      examined. Activity was recorded either after a single orthodromic stimulation,
      which gave rise to paroxysmal depolarization shift (PDS), or during a 500 msec
      train of 50 Hz stimulation, which produced a sustained depolarization. In the CA1
      and CA3 areas, both the PDS and sustained depolarization were reduced by APV (20
      microM) and ketamine (100 microM). APV reduced the area under the PDS by 24 +/-
      3% and 32 +/- 4% in CA1 and CA3 neurons, respectively. The corresponding
      reductions in the sustained depolarization were 10 +/- 2% and 22 +/- 4%. Ketamine
      reduced the PDS by 43 +/- 4% and 31 +/- 4% in CA1 and CA3 and decreased the
      sustained depolarization by 21 +/- 3% and 12 +/- 3%. In all cases, NMDA receptor
      antagonists had a significantly greater effect on the PDS than the sustained
      depolarization. These results indicate that, although not essential for
      generation of paroxysmal activity, NMDA receptors make significant contributions
      to epileptiform activity in both CA1 and CA3 regions of the hippocampus.

PMID- 1974848
TI  - Superoxol and aminopeptidase tests for identification of pathogenic Neisseria
      species and Moraxella (Branhamella) catarrhalis.
AB  - The superoxol test, and prolyl aminopeptidase and gammaglutamyl aminopeptidase
      tests were evaluated for the detection of pathogenic Neisseria spp. using 317
      strains of Neisseria-ceae. The superoxol test was positive for all 116 gonococci
      and 62 Moraxella (Branhamella) catarrhalis strains, but also for three strains of
      Neisseria meningitidis, one strain of Neisseria lactamica and eight saprophytic
      neisseriae. When using strains grown on Thayer-Martin medium, the positive and
      negative predictive values of the superoxol test for the identification of
      Neisseria gonorrhoeae were 96.7% and 100% respectively. Meningococci were the
      only neisseriae growing on Thayer-Martin medium that showed gamma-glutamyl
      aminopeptidase activity. The prolyl aminopeptidase test showed low specificity.

PMID- 1974849
TI  - Characterization of the coated vesicle uncoating ATPase: tissue distribution,
      association with and activity on intact coated vesicles.
AB  - We have analyzed the uncoating process of clathrin-coated vesicles (CV) performed
      by an ATPase (UA; apparent molecular mass 70 kDa) prepared from various mammalian
      tissues. Our data show that this enzyme removes the clathrin coat from isolated,
      intact coated vesicles, as seen by sedimentation analysis on gels and also by
      electron microscopy. The isolated UA does not discriminate between CV from
      homologous or heterologous tissues. This finding implies that the brain-specific
      insertion in clathrin light chains cannot be essential for the binding of brain
      UA to target vesicles. Polyclonal antibodies were raised against UA and were
      found to inhibit UA activity. Immunoblotting of purified CV and immunoblotting of
      CV in situ indicate that a subpopulation of CV contains bound UA. However, most
      of the uncoating enzyme is not associated with coated structures in mammalian
      tissue culture cells. Our data support the hypothesis that the 70 kDa uncoating
      ATPase is responsible for the in vivo uncoating of coated vesicles.

PMID- 1974850
TI  - A bidirectional regulatory network involving IL 2 and IL 4 in the alternative CD2
      pathway of T cell activation.
AB  - In this study we examined the effect of interleukin 4 (IL 4) on T cell activation
      and proliferation via the alternative CD2 pathway. To this end highly purified
      human resting T cells were cultured with a stimulating pair of anti-CD2
      monoclonal antibodies in the absence of accessory signals from monocytes.
      Addition of either recombinant (r)IL 2 or rIL 4 resulted in proliferation of the
      anti-CD2-stimulated T cells. The growth-promoting effect of rIL 4 on
      preactivated. T cells was shown to be partly a direct effect. rIL 4 also induced
      IL 2 production and, as a consequence, the effect of rIL 4 on T cell growth was
      enhanced by endogenously produced IL 2. Moreover, rIL 4 acted in synergy with
      exogenously added rIL 2 in promoting growth of anti-CD2-stimulated T cells. The
      synergistic effect of IL 2 and IL 4 could be explained by IL 2-induced up
      regulation of IL 4 responsiveness. In contrast, preincubation with rIL 4 did not
      enhance IL 2 responsiveness and rIL 2 but not rIL 4 up-regulated IL 2R expression
      on anti-CD2-stimulated T cells. Finally we could demonstrate that monocyte
      produced cytokines (IL 1 and IL 6) enhance the proliferative response to rIL 4 of
      anti-CD2-stimulated T cells. It can be concluded that IL 4 can act as a paracrine
      growth factor for T cells activated in the alternative CD2 pathway, and that it
      acts synergistically with IL 2, IL 1 and IL 6. Moreover, IL 4 is a helper signal
      for IL 2 production. Thus, IL 2 and IL 4 are involved in a bidirectional
      regulatory network, with IL 4 as an inducer of IL 2 production, and IL 2 as an
      enhancer of IL 4 responsiveness.

PMID- 1974851
TI  - CD4+ T cells in murine acquired immunodeficiency syndrome: evidence for an
      intrinsic defect in the proliferative response to soluble antigen.
AB  - C57BL/6 mice inoculated with LP-BM5 murine leukemia viruses develop an
      immunodeficiency syndrome, termed murine acquired immunodeficiency syndrome
      (MAIDS), characterized by a variety of functional abnormalities of T and B cells.
      In the present study, we have analyzed the ability of lymph node cells from
      infected mice to generate secondary in vitro proliferative responses to soluble
      antigens. Our data demonstrate that the ability of lymph node cells to
      proliferate in response to soluble antigen or T cell mitogens declines
      progressively during the course of MAIDS. Impaired proliferative responses were
      shown to be characteristic of purified CD4+ but not CD8+ cells from infected mice
      when stimulated in the presence of normal accessory cells. In addition, the
      impaired responses of unseparated lymph node cells from infected mice could be
      reconstituted by the addition of purified CD4+ T cells from nodes of primed
      normal animals. These results strongly suggest that an intrinsic CD4+ T cell
      defect developing during the course of MAIDS contributes significantly to
      impaired responses to mitogens and to impaired secondary in vitro proliferative
      responses to soluble antigen.

PMID- 1974853
TI  - Reversal of the acute effects of 3,4-methylenedioxymethamphetamine by 5-HT uptake
      inhibitors.
AB  - Recent evidence suggests that the acute 3,4-methylenedioxymethamphetamine (MDMA)
      induced loss of tryptophan hydroxylase activity (TPH) may be due to the oxidation
      of critical sulf-hydryl groups on the molecule. To determine if TPH activity
      could be regenerated in vivo we administered a 5-HT uptake inhibitor at various
      times immediately after MDMA. Although enzyme activity began to decline
      immediately following MDMA administration, rats receiving the uptake inhibitor 1
      h post MDMA showed a rapid recovery of TPH activity. Administration of an uptake
      inhibitor 3 h post MDMA was without effect on the time course of TPH
      inactivation. The results suggest that systems exist within the serotonergic
      neuron for the reductive regeneration of active TPH. Furthermore, these systems
      are acutely compromised following the administration of MDMA.

PMID- 1974852
TI  - Cytotoxic alpha/beta+ and gamma/delta+ T cells in murine intestinal epithelium.
AB  - Murine intraepithelial lymphocytes (IEL) consist of two main populations.
      Approximately half are Thy-1+, most of which are CD3+, T cell receptor (TcR)
      alpha/beta+, and the remainder are Thy-1-, most of which are CD3+, TcR alpha/beta
      (presumably TcR gamma/delta+). In redirected cytotoxicity assays, TcR
      alpha/beta+ IEL are potent cytotoxic effectors. Thy-1-, CD3+, TcR alpha/beta- IEL
      isolated from athymic mice are also cytotoxic. Thus, regardless of TcR usage or
      Thy-1 expression, IEL are cytotoxic effectors.

PMID- 1974854
TI  - Differential recovery of dopamine synthetic enzymes following MPTP and the
      consequences of GM1 ganglioside treatment.
AB  - After 7 days of treatment with MPTP (1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine), 30 mg/kg i.p., tyrosine hydroxylase (TH) and aromatic L
      amino acid decarboxylase (AAAD) activities are decreased by more than 50% in the
      mouse striatum. Within 30 days, AAAD activity returns while TH activity remains
      depressed. TH activity can be restored to near normal by chronic treatment with
      GM1 ganglioside, 30 mg/kg i.p.

PMID- 1974855
TI  - Region-specific noradrenaline depletion by neonatal DSP-4: functional
      consequences and effect on a coexisting neurotransmitter.
AB  - Noradrenaline (NA) depletion following neonatal treatment of rats with DSP-4 (N
      (2-chloroethyl)-N-ethyl-2-bromobenzyl-amine) was not accompanied by any changes
      in neuropeptide tyrosine (NPY) levels. After 85-95% NA depletion in the spinal
      cord of DSP-4-treated rats, the reaction time in the tail withdrawal test was
      shorter than in the controls but the endogenous activation of the sympathetic
      nervous system in the baroreceptor reflex remained unchanged. These results
      suggest that the NA neurons in the spinal cord have an inhibitory function the
      processing of incoming sensory information.

PMID- 1974856
TI  - Discriminatory roles for D1 and D2 dopamine receptor subtypes in the in vivo
      control of neostriatal cyclic GMP.
AB  - The D1 and D2 subtypes of the dopamine receptor have been distinguished by their
      opposing effects on levels of neostriatal cyclic adenosine monophosphate (cAMP).
      The studies reported here show that the content of cyclic guanosine monophosphate
      (cGMP) in the mouse neostriatum is modulated by dopaminergic drugs in a manner
      which also discriminates D1 and D2 receptors. D1 receptor stimulation with SKF
      38393 produced up to 90%, dose-related increases in neostriatal cGMP, whereas D1
      antagonism with SCH 23390 decreased cGMP by 30% and blocked the increase induced
      by SKF 38393. D2 receptor stimulation with quinpirole did not alter cGMP levels
      whereas D2 antagonism increased cGMP by 40-60% after haloperidol and by up to
      100% after sulpiride. The increases in neostriatal cGMP levels following D1
      agonism were potentiated in an additive manner by haloperidol. Thus, neostriatal
      cGMP content is positively controlled by D1 agonism and negatively controlled by
      or unlinked to the D2 receptor. The reciprocal control of neostriatal cGMP levels
      by D1- and D2-selective compounds may contribute to the separate as well as
      combined actions of D1 and D2 ligands.

PMID- 1974857
TI  - The rise of body temperature induced by the stimulation of dopamine D1 receptors
      is increased in acutely reserpinized mice.
AB  - In naive mice, the selective D1 agonist, SK&F 38393 (7.5-30 mg/kg s.c.), induced
      a significant rise of body temperature (0.5-1 degree C) which was antagonized by
      SCH 23390 (100 micrograms/kg s.c.) and by flupenthixol (0.4 mg/kg i.p.). In mice
      treated with reserpine (5 mg/kg s.c.) 18 h before testing, which on its own
      caused intense hypothermia (10-12 degrees C), SK&F 38393 (1.87-30 mg/kg s.c.)
      induced a dose-dependent and more marked rise of body temperature (5-7 degrees
      C). Similarly, SK&F 38393 (30 mg/kg s.c.) partially prevented reserpine-induced
      hypothermia. The central origin of the SK&F 38393 effects in reserpine-treated
      mice is indicated by the rise of body temperature induced by the i.c.v.
      administration of the drug (12.5-50 micrograms per mice). The SK&F 38393-induced
      rise of body temperature in acutely reserpinized mice was antagonized by SCH
      23390 (50-200 micrograms/kg s.c.), clozapine (1.87-30 mg/kg i.p.) or
      chlorpromazine (2-32 mg/kg i.p.) but not by metoclopramide (25 or 100 mg/kg i.p.)
      or amisulpride (12.5 or 50 mg/kg). In naive mice, apomorphine (1 mg/kg s.c.) or
      LY 171555 (0.4 mg/kg s.c.) induced hypothermia which was antagonized by
      amisulpride (12.5 mg/kg i.p.); a transiently increased body temperature was even
      measured 30 min after apomorphine injection in amisulpride-treated mice.
      Apomorphine (1 mg/kg s.c.) induced a rise of body temperature in acutely
      reserpinized mice which was significantly reduced by SCH 23390 (50 and 200
      micrograms/kg s.c.) and significantly increased by amisulpride (12.5 and 50 mg/kg
      i.p.). These data suggest that pharmacologically different dopamine receptor
      subtypes mediate different effects on body temperature in mice: D1 dopamine
      receptors mediate a rise of body temperature which is increased in hypothermic
      reserpinized animals and dopamine receptors of the D4 subtype mediate the
      decrease of body temperature in naive mice.

PMID- 1974858
TI  - Antagonism of the neurotoxicity due to a single administration of
      methylenedioxymethamphetamine.
AB  - The role of transmitter release in the serotonergic neurotoxicity of
      methylenedioxymethamphetamine (MDMA) was examined using treatments altering MDMA
      induced release or its consequences. The long-term decrease in 5-HT
      concentrations and tryptophan hydroxylase activity produced by MDMA was
      antagonized by depletion of vesicular monoamines with reserpine or interruption
      of monoamine synthesis with the decarboxylase inhibitor, monofluoromethyl DOPA
      (dihydroxyphenylalanine). Similar results were achieved by selectively inhibiting
      dopamine synthesis with alpha-methyl-p-tyrosine or through bilateral lesions of
      the substantia nigra with 6-hydroxydopamine. The dopamine receptor antagonist
      haloperidol was also effective in this regard. Although these results strongly
      implicate dopamine release in the long-term neurochemical effects of MDMA,
      protection was also provided by selective 5-HT2 antagonists indicating that the
      neurotoxicity is dependent upon the release of both dopamine and 5-HT.

PMID- 1974859
TI  - The melanocortin receptor in the rat lacrimal gland: a model system for the study
      of MSH (melanocyte stimulating hormone) as a potential neurotransmitter.
AB  - The melanocortin receptors in intraorbital and extraorbital rat lacrimal glands
      were studied with [125I][Nle4,D-Phe7]alpha MSH as radioligand and with several
      unlabeled melanocortin peptides. The pharmacological properties of the
      melanocortin receptor in both tissues appeared to be essentially identical.
      Receptor binding was studied in a membrane fraction sedimented at 12,000-100,000
      X g, establishing for [125I][Nle4,D-Phe7]alpha MSH a KD of 0.76 and 2.2 nM for
      the intra- and extraorbital glands, respectively. Binding of the radioligand was
      competitively inhibited by alpha MSH (alpha-melanocyte stimulating hormone) and
      ACTH-(1-24) with IC50 values in the submicromolar range. MSH binding in both
      tissues was abolished by EGTA and was increased dose dependently with elevation
      of free Ca2+ ion concentration. The half-maximal effect on MSH binding was
      obtained around 200 microM Ca2+ and maximal binding was reached at nearly 2 mM
      free Ca2+ in membrane preparations from both tissues. The calmodulin-binding
      peptides, melittin, mastoparan and M5, the latter being the 18-amino acid
      synthetic analogue of the C-terminal calmodulin-binding domain of myosin light
      chain kinase, inhibited MSH binding in the concentration range of 1-20 microM.
      Macroscopic autoradiographic analysis of cryosections prepared from either
      lacrimal gland to which [125I][Nle4,D-Phe7]alpha MSH was subsequently bound,
      showed the melanocortin receptor to be uniformly distributed within the acinar
      lobes. At the microscopic level, MSH was found to be associated with the acinar
      cells, primarily at the basal perinuclear region. Peroxidase secretion from
      extraorbital lacrimal slices was stimulated by MSH, epinephrine and
      carbamylcholine to a similar extent. The response of the tissue to stimulation by
      MSH was however not blocked by alpha/beta-adrenoceptor blockers or by atropine,
      suggesting that MSH acts as a primary secretagogue in this tissue. Thus, this
      system seems to be uniquely suited to serve as a model for the study of both the
      molecular and pharmacological details of the action of MSH and other
      melanocortins in a non-melanogenic tissue.

PMID- 1974860
TI  - Reversal of alpha-adrenoceptor blockade by propranolol in isolated rat pulmonary
      artery.
AB  - Pulmonary artery rings were prepared from rats (group I to VI, n = 5-7 per group)
      in order to investigate if a beta-adrenoceptor antagonist interferes with the
      effect of alpha-adrenoceptor blockade. In I, four cumulative noradrenaline (NA)
      dose-response curves (10(-9) to 10(-3) M) were constructed. In II, NA curves were
      constructed first, without blockers, then in the presence of phentolamine (10(-6)
      M), then propranolol (10(-8) M), then phentolamine plus propranolol (10(-8) M).
      III, IV and V were treated similar to II, except that atenolol (10(-8) M), ICI
      118,551 (10(-8) M) and propranolol (10(-6) M), respectively, were added instead
      of propranolol (10(-8) M). In VI, NA (10(-6) M) was added followed by
      phentolamine and then propranolol (10(-9) to 10(-6) M). Phentolamine shifted the
      NA curve to the right with an increase in the EC50 value. Propranolol but not
      atenolol or ICI 118,551, reduced the elevated EC50 values caused by phentolamine.
      In group VI, the increase in force by NA was reduced by phentolamine; the effect
      of phentolamine was completely abolished by propranolol. Thus, propranolol
      interferes with the effect of phentolamine in the rat pulmonary artery.

PMID- 1974861
TI  - Increased cell surface EGF receptor expression during the butyrate-induced
      differentiation of human HCT-116 colon tumor cell clones.
AB  - Several clonal sublines of HCT-116 human colon adenocarcinoma cells were isolated
      and characterized on the basis of their growth characteristics, intrinsic
      enterocyte-like differentiation (as assessed by alkaline phosphatase and lactase
      activities), and responses to butyrate, an inducer of colon tumor cell
      maturation. The HCT-116 sublines were found to be heterogeneous and several
      phenotypically distinct clones were identified. Further characterization of these
      clones indicated that the effects of butyrate on cell growth, alkaline
      phosphatase activity, and lactase activity were distinct and separable. The
      growth of all of the clones were inhibited by butyrate (IC50 values varied from
      0.44 to 1.5 mM), but the effects of this agent on alkaline phosphatase and
      lactase activities varied widely. In several sublines butyrate had no effect on
      either enzyme while in others one or both activities were induced. Additionally,
      the binding of 125I-epidermal growth factor (EGF) to cell surface receptors was
      found to be proportional to the expression of lactase activity in the cell. The
      D3 clone and other sublines with intrinsic lactase activities greater than 100
      nmol/mg/min expressed a class of high-affinity EGF receptors (e.g., D3 cells had
      3.48 X 10(4) EGF receptors/cell with a kd of 0.61 nM). Other clones with less
      lactase activity had undetectable levels of 125I-EGF binding. In clones which
      exhibited greater than twofold increases in lactase activity in response to
      butyrate, the expression of a large number of low-affinity EGF receptors was also
      induced. In one such clone, the P1 subline, lactase activity was increased from
      70 nmol/mg/min to 230 nmol/mg/min after 96 h in 2 mM butyrate, and the expression
      of EGF receptors was increased from undetectable levels to 1.18 X 10(5) EGF
      receptors/cell (kd of 3.2 nM). Northern blot analysis indicated that the
      increased 125I-EGF binding after butyrate treatment may have been due, in part,
      to a greater than twofold accumulation of EGF receptor mRNA. In addition, the
      expression of the messages for transforming growth factor alpha (TGF-alpha) and
      transforming growth factor beta (TGF-beta) was examined in butyrate-treated
      cells. While TGF-alpha mRNA levels were found to correlate with EGF receptor
      message levels in the HCT-116 clones, TGF-beta mRNA expression was not found to
      correlate with the butyrate-induced growth inhibition or with increases in EGF
      receptor expression, alkaline phosphatase activity, or lactase activity in these
      cells.

PMID- 1974862
TI  - Expression of growth factor and growth factor receptor RNA in rat pleural
      mesothelial cells in culture.
AB  - Mineral fiber-induced pleural mesothelioma in the rat is a suitable model for
      asbestos-induced mesothelioma in humans. A proposed mechanism for the genesis of
      mesotheliomas is the initiation of an autocrine pathway leading to unregulated
      growth of the mesothelium. To understand if changes in the expression of mRNA of
      critical growth factors and receptors occur in target mesothelial cells, it is
      first necessary to characterize the pattern of expression of these genes in
      normal mesothelial cells. Rat mesothelial cells were isolated from the parietal
      pleura and strains of these cells were propagated in vitro. The cells were
      diploid, had epithelial gross morphology and ultrastructure, and coexpressed
      keratins and vimentin. Northern blot analysis demonstrated that the cells
      expressed transforming growth factor beta 1 and fibroblast growth factor.
      Transcripts for transforming growth factor alpha, platelet-derived growth factor
      A-chain, and platelet-derived growth factor B-chain were not detected. Receptors
      for platelet-derived growth factor, epidermal growth factor, and insulin were
      detected. Although normal mesothelial cells express receptors for these growth
      factors, no production of their corresponding ligands by these cells could be
      detected, suggesting that autocrine stimulation of growth via the production of
      such factors may be specific to transformed mesothelial cells.

PMID- 1974863
TI  - Differential effect of L3T4+ cells on recovery from total-body irradiation.
AB  - We have examined the importance of L3T4+ (murine equivalent to CD4+) cells for
      hematopoietic regulation in vivo in unperturbed mice and mice recovering from
      total-body irradiation (TBI) using a cytotoxic monoclonal antibody (MoAb) raised
      with the GK 1.5 hybridoma. Ablating L3T4+ cells in "normal" (unperturbed) B6D2F1
      mice substantially decreased the S-phase fraction (determined by in vivo
      hydroxyurea suicide) of erythroid progenitor cells (erythroid colony-forming
      units, CFU-E) as compared to the pretreatment level (10% +/- 14.1% [day 3
      following depletion] vs 79.8% +/- 15.9%, respectively) with a corresponding
      decrease in the marrow content of CFU-E at this time to approximately 1% of the
      pretreatment value. Although the S-phase fraction of CFU-GM was decreased to 2.2%
      +/- 3.1% 3 days after L3T4+ cell ablation from the 21.3% +/- 8.3% pretreatment
      value, CFU-GM cellularity showed little change over the 3 days following anti
      L3T4 treatment. Anti-L3T4 MoAb treatment had little or no effect on either the S
      phase fraction or the marrow content of hematopoietic "stem cells" (spleen colony
      forming units, CFU-S) committed to myeloerythroid differentiation. Ablating L3T4+
      cells prior to a single dose of 2 Gy TBI resulted in significantly reduced marrow
      contents of CFU-S on day 3 and granulocyte-macrophage colony-forming units (CFU
      GM) on day 6 following TBI, with little or no effect on the corresponding
      recovery of CFU-E. The present findings provide the first in vivo evidence that
      L3T4+ cells are involved in: 1) maintaining the proliferative activity of CFU-E
      and CFU-GM in unperturbed mice and 2) supporting the restoration of CFU-S and CFU
      GM following TBI-induced myelosuppression.

PMID- 1974864
TI  - A simplified method for enrichment of mouse hematopoietic stem cells.
AB  - A simplified method for enriching mouse hematopoietic stem cells using standard
      two-color fluorescence-activated cell sorting (FACS) has been developed. By
      eliminating one fluorescence parameter from a previously described four-parameter
      (three-color) method, FACS enrichment of mouse hematopoietic stem cells to a
      purity within twofold of that accomplished by the more complex method could be
      achieved using a single-laser, two-color FACS instrument. The method involves
      positive selection of mouse bone marrow cells expressing the Ly-6A.2 molecule
      (previously termed stem cell antigen-1, or Sca-1) and negative selection for
      expression of a number of cell surface markers characteristic of differentiated
      cells of hematolymphoid lineages (Lin-). Cell populations selected by this method
      contain 480 +/- 100 day-13 splenic colony-forming units (CFUs-13) per 10(4)
      cells, whereas the day-8 splenic colony-forming unit (CFUs-8) content is about
      tenfold lower. The frequency of thymic colony-forming units (CFUt) is about one
      in ten cells. Long-term hematopoietic repopulation of irradiated animals was
      observed following the transfer of 60-100 cells. However, as few as 20 cells
      could mediate radioprotection of lethally irradiated mice. An analysis of the
      cell surface phenotype of isolated Ly-6A.2+Lin- cells showed that 30%-50%
      expressed low levels of the Thy-1 antigen and that the CFUs-13 activity was
      predominantly associated with the Thy-1lo cells. The Ly-6A.2+Lin- cells expressed
      intermediate levels of phagocyte glycoprotein-1 (Pgp-1), low levels of heat
      stable antigen (HSA), and high levels of class I major histocompatibility
      antigens (H2 K/D), leukocyte common antigen (Ly-5), and carbohydrate binding
      sites for the lectin wheat-germ agglutinin (WGA). By these criteria, Ly-6A.2+Lin-
      cells are phenotypically similar to mouse hematopoietic stem cells isolated by
      other methods.

PMID- 1974866
TI  - [The psychotropic properties of bonnecor and ethacizine].
AB  - The comparative study of the psychotropic activity of new acyl derivatives of
      dibenzazepine and phenothiazine--bonnecor (chlorhydrate 3-carbethoxyamino
      5(dimethylaminoacetyl) dibenzazepine and ethacizine (chlorhydrate 2
      carbethoxyamino-10-(beta-diethyl-aminopropionyl)phenothiazine)--in the
      experiments on small laboratory animals showed the presence of the
      antidepressive, anxiolytic, antiamnesic and antihypoxic effects. The drugs
      exerted the psychotropic effects at administration in the doses exceeding those
      which influence the cardiovascular system. By the degree of the anxiolytic action
      bonnecor and ethacizine are inferior to diazepam, are as potent as trioxasine and
      are superior to meprobamat. The noted psychotropic action by its character and
      degree can serve as a beneficial supplement to the spectrum of the
      pharmacological activity of the studied compounds.

PMID- 1974867
TI  - mRNA levels and methylation patterns of the tyrosine aminotransferase gene in
      aging inbred rats.
AB  - We have examined the mRNA levels and methylation patterns of the liver-specific
      tyrosine aminotransferase (TAT) gene in inbred female rats aged 6, 24 and 36
      months. Northern hybridization analysis of total RNA showed a 65% decrease in the
      steady state transcript level of TAT in the liver of 24- and 36-month old rats as
      compared to 6-month old animals. The TAT gene as studied by Southern
      hybridization analysis using the isoschizomers Hpa II and Msp I was found to be
      hypomethylated in the liver as compared to spleen and brain at six CpG sites
      within the gene. Methylation at these sites remained unchanged during aging.

PMID- 1974865
TI  - Release of glutamate and aspartate from the visual cortex of the cat following
      activation of afferent pathways.
AB  - To test the possibility that glutamate (Glu) and aspartate (Asp) are transmitters
      at geniculo-cortical synapses in the visual cortex of the cat, we studied the
      release of amino acids from the striate cortex consequent upon visual and
      electrical stimulation of the dorsal lateral geniculate nucleus (LGN) and of the
      optic tract, using push-pull cannulae. We perfused a discrete region that
      included layer IV of the cortex with an artificial cerebrospinal fluid (aCSF) and
      analysed the amino acid content of these perfusates by high-performance liquid
      chromatography (HPLC). Significant increases only of Glu and Asp were obtained
      among all 17 amino acids measured, except for gamma-aminobutyric acid (GABA),
      during electrical stimulation of the afferent pathways. Visual stimulation by
      stroboscopic diffuse flashes of light increased the level of Glu released, but
      did not change that of Asp significantly. The level of GABA released did not
      change during diffuse flash stimulation, suggesting that the increase in Glu was
      not derived from cortical neurons. The increases in release of Glu/Asp were not
      seen when the perfusion medium was replaced with a Ca2(+)-free, high-Mg2(+)
      containing solution. The basal (resting) release of Glu/Asp in the absence of
      stimulation also was decreased during perfusion with Ca2(+)-free/high-Mg2+
      solutions. Intraocular injections of a sodium channel blocker, tetrodotoxin
      (TTX), resulted in a remarkable decrease in the basal release of Glu. These
      results suggest that Glu is released as in excitatory synaptic transmitter at
      least from terminals of geniculo-cortical afferents and Asp from axons of a
      certain type of visual cortical neuron.

PMID- 1974868
TI  - Atrial natriuretic factor recognizes two receptor subtypes in endothelial cells
      cultured from bovine pulmonary artery.
AB  - In this study specific high affinity binding sites for atrial natriuretic factor
      (rANF(99-126] have been identified on cultured endothelial cells of bovine
      pulmonary artery origin (BPAEC). A time-dependent rise in cellular cGMP levels
      stimulated by rANF(99-126) was followed by release of the nucleotide into the
      incubation medium. The use of truncated, ring-deleted and linear atrial peptide
      analogs in competitive displacement analysis and measurement of cGMP accumulation
      indicated that only a minor proportion (5-11%) of the available receptor pool was
      of the ANF-B receptor subtype, linked to guanylate cyclase, with the remaining
      major proportion possibly of the ANF-C (clearance) receptor subtype. The
      existence of two ANF receptor subtypes in this cell culture model would suggest a
      significant role for the circulating peptide in modulation of pulmonary
      endothelial cell function, which would influence or complement its direct actions
      on the underlying vasculature of the pulmonary circulation.

PMID- 1974869
TI  - Inhibition of gamma-glutamyl transpeptidase decreases amino acid uptake in human
      keratinocytes in culture.
AB  - Acivicin inhibits gamma-glutamyl transpeptidase activity in human keratinocytes
      in culture. Treatment of these cells with acivicin produces a decrease in the
      uptake of L-[U-14C]alanine, 2-amino-[1-14C]-isobutyrate, L-[U-14C]leucine and 1
      aminocyclopentane-1-[14C]carboxylate. D-[U-14C]glucose uptake is not affected by
      the presence of acivicin. These results support, for the first time in vitro, the
      hypothesis that the gamma-glutamyl cycle may be involved in amino acid uptake by
      human cells.

PMID- 1974870
TI  - Intestinal mesenchyme provokes differentiation of intestinal endocrine cells in
      gizzard endoderm.
AB  - The gizzard (muscular stomach) of chicks is deficient in endocrine cells at
      hatching. It has previously been shown that proventricular types and proportions
      of endocrine cells can be induced in gizzard endoderm under the influence of
      proventricular (glandular stomach) mesenchyme. In order to test its capacity to
      form nongastric endocrine cell types, gizzard endoderm of 3.75- to 5-day chick
      embryos was combined with mesenchyme from the small intestine of 3.5- to 4-day
      quail embryos. The combinations were grown as chorio-allantoic grafts until they
      attained an incubation age comparable to that of hatching chicks. Controls
      comprised reassociated endoderm and mesenchyme of chick gizzard and of quail
      intestine. In the experimental grafts, morphogenesis was predominantly intestinal
      but some grafts showed gizzard-like features, particularly if the endoderm had
      been provided by older donors. All intestinal endocrine cell types, including
      those also found in the normal proventriculus (serotonin-, glucagon-, pancreatic
      polypeptide-, neurotensin- and somatostatin-immunoreactive cells) differentiated
      in experimental grafts, some even where morphogenesis was gizzard-like. Hence
      progenitors of not only gastric, but also intestinal, endocrine cells are indeed
      present in gizzard endoderm. The possibility that gizzard mesenchyme is
      inhibitory to endocrine cell differentiation is mooted. Motilin- and secretin
      immunoreactive cells, which are characteristic of the intestine but not of the
      proventriculus of chicks at hatching, were respectively sparse or absent when the
      endoderm was derived from older donors. Thus the ability of gizzard endoderm to
      differentiate into nongastric endocrine cell types declines before its capacity
      to form gastric types. The unexpected appearance of gastrin-releasing peptide
      (GRP)-immunoreactive cells, a proventricular type not found in normal chick
      intestine, suggests that the intestinal mesenchyme, at least in this instance,
      was exercising a permissive role.

PMID- 1974872
TI  - [Sea-urchin injuries].
AB  - Sea urchins (Echinoidea) are found along the Mediterranean and especially the Red
      Sea coasts of Israel. The most important species are Diadema setosum on the Red
      Sea coast, and Paracentrus lividus on the Mediterranean. When stepped on, the
      brittle spines penetrate and the venom they carry causes further damage. Thus the
      injuries are mainly mechanical, but may be complicated by a foreign body reaction
      to the bits of spine, to small detached segments of their covering epithelium,
      and damage by the epithelial venom. Severe pain, edema, local sensory loss and
      sometimes suppuration ensue.

PMID- 1974871
TI  - In vitro studies of the effect of buflomedil on platelet responsiveness.
AB  - The effect of buflomedil (Fonzylane; Laboratoire Lafon, Maisons-Alfort, France)
      on platelet function, a drug used clinically for the treatment of peripheral
      vascular diseases, was investigated in vitro. The compound significantly inhibits
      epinephrine-induced aggregation at the micromolar level. At higher doses
      (approximately 1 mM), a weak inhibition of ADP- and collagen-induced aggregation
      was observed; at these concentrations, buflomedil inhibits granular secretion and
      the interaction of fibrinogen with its receptor on platelet. Further
      investigations indicate that the drug affects calcium uptake at the membrane
      level and inhibits the binding of [3H]-yohimbine to the same extent as observed
      with phentolamine. The IC50 determined from competition binding assays was 1 +/-
      0.5 microM. This value was consistent with the affinity constant approximated for
      the binding of [3H]-buflomedil to non-stimulated platelets. Taken-together, these
      results indicate that the vasoactive compound buflomedil is a weak
      antiaggregating agent which exhibits alpha 2-adrenergic antagonistic properties.

PMID- 1974873
TI  - Laboratory assessment of P-glycoprotein in cancer chemosensitivity testing.

PMID- 1974874
TI  - Immunohistochemical analysis of P-glycoprotein expression correlated with
      chemotherapy resistance in locally advanced breast cancer.
AB  - We analyzed the expression of P-glycoprotein in samples from 48 patients with
      locally advanced breast cancer. Tumor samples from 40 patients were obtained at
      mastectomy, which was performed after three cycles of induction chemotherapy
      consisting of doxorubicin, cyclophosphamide, vincristine, and prednisone. P
      glycoprotein expression distributed focally was observed in 20 tumors by the
      immunoperoxidase method using the anti-p170-monoclonal antibody C219. The
      percentage of the tumor cell population expressing P-glycoprotein varied from
      less than 5% to greater than 30%; expression was observed significantly more
      often in tumors that showed less than partial response to the preoperative
      chemotherapy. Furthermore, P-glycoprotein was not expressed in eight tumor
      specimens obtained at the time of diagnosis, prior to chemotherapy, from patients
      who subsequently had pathologic complete responses. A comparative study of P
      glycoprotein expression before and after chemotherapy and upon recurrence of
      tumor was done on a limited number of samples. No significant differences in P
      glycoprotein expression were found. Therefore, it is possible that an intrinsic,
      rather than acquired, drug resistance may play a role in the failure of induction
      chemotherapy for locally advanced breast cancer.

PMID- 1974875
TI  - Immunocytochemical localization and identification of prosomatostatin gene
      products in medullary carcinoma of human thyroid gland.
AB  - Thirty-three cases of histologically proven calcitonin-positive medullary thyroid
      carcinoma were studied immunocytochemically for the occurrence of prosomatostatin
      related peptides. Positive cells, identified with a panel of antisera raised
      against four different regions of the prosomatostatin molecule, were found in
      100% of the tumors. Most but not all somatostatin-positive cells were also
      immunoreactive for calcitonin. Notably, seven patients harboring somatostatin
      rich tumors revealed a more favorable clinical course. The results (1) indicate
      that somatostatin production is a universal concomitant of thyroid medullary
      carcinoma, (2) suggest that these cells are likely to produce a somatostatin
      precursor molecule similar to mammalian prosomatostatin, and (3) imply that
      somatostatin-reactive cells may have as yet unknown roles in these tumors,
      possibly in the realm of paracrine and autocrine regulation of cell growth.

PMID- 1974876
TI  - cDNA cloning, mRNA distribution and heterogeneity, chromosomal location, and RFLP
      analysis of human osteopontin (OPN).
AB  - A human osteopontin (OP) cDNA was isolated from a library made from primary
      cultures of human bone cells. The distribution of osteopontin mRNA in human
      tissues was investigated by Northern analysis and showed that the human message
      was predominant in cultures of bone cells and in decidua cells isolated at 6-12
      weeks of gestation. Immunohistochemical analysis confirmed that OP expression is
      high in decidua cells as well as in the endometrial glands of a non-pregnant
      secretory-phase human uterus. Two variants of the OP message were evident on the
      basis of DNA sequencing and polymerase chain reaction amplification of bone and
      decidua cell mRNA. The peptides potentially translated by the variant messages
      differ by the presence (OP1b) or absence (OP1a) of 14 amino acids at residue 58
      of the molecule. The deduced human protein sequence shows a conservation between
      species in the position of the Arg-Gly-Asp (RGD) cell attachment site.
      Chromosomal mapping of the osteopontin gene (OPN) using human-rodent cell hybrids
      demonstrated a location on chromosome 4 in the human genome. In situ
      hybridization of metaphase chromosomes using radiolabeled OP1a as a probe
      indicated that the gene is located on a region of 4q that is near the centromere.
      A high-frequency restriction fragment length polymorphism was evident in the DNA
      from 29 unrelated individuals using the enzyme BglII. Analysis of total genomic
      DNA by digestion with several restriction enzymes, Southern blotting, and
      hybridization with the human osteopontin cDNA indicated that the gene is a single
      copy with an approximate length of 5.4-8.2 kb.

PMID- 1974877
TI  - A physical map of the human Y-chromosome short arm.
AB  - A physical map of the Y-chromosome short arm was constructed using DNA probes
      p19B, Y-286/la5, pZFY, Y-280, and Y-227. These probes hybridize with four NotI
      fragments of 400 kb (p19B and Y-286/la5), 350 kb, 1.9 Mb, and 3.0 Mb,
      respectively. The restriction fragments were shown to be adjacent to each other
      by analysis of NotI partial digests, overlapping restriction fragments, and/or
      the detection of rearranged restriction fragments in a 46,XX male. The present
      map covers approximately 5.6 Mb of contiguous DNA of Yp. Previously, the size of
      the pseudoautosomal region was estimated to be 2.3 Mb, and a 5.3-Mb NotI fragment
      containing Y-specific repeated DNA was assigned to proximal Yp. These and the
      present data account for approximately 13 Mb and thus for most of the DNA content
      of the Y short arm.

PMID- 1974878
TI  - Informativeness of human (dC-dA)n.(dG-dT)n polymorphisms.
AB  - Abundant human interspersed repetitive DNA sequences of the form (dC-dA)n.(dG
      dT)n have been shown to exhibit length polymorphisms. Examination of over 100
      human (dC-dA)n.(dG-dT)n sequences revealed that the sequences differed from each
      other both in numbers of repeats and in repeat sequence type. Using a set of
      precise classification rules, the sequences were divided into three categories:
      perfect repeat sequences without interruptions in the runs of CA or GT
      dinucleotides (64% of total), imperfect repeat sequences with one or more
      interruptions in the run of repeats (25%), and compound repeat sequences with
      adjacent tandem simple repeats of a different sequence (11%). Informativeness of
      (dC-dA)n.(dG-dT)n markers in the perfect sequence category was found to increase
      with increasing average numbers of repeats. PIC values ranged from 0 at about 10
      or fewer repeats to above 0.8 for sequences with about 24 or more repeats. (dC
      dA)n.(dG-dT)n polymorphisms in the imperfect sequence category showed lower
      informativeness than expected on the basis of the total numbers of repeats. The
      longest run of uninterrupted CA or GT repeats was found to be the best predictor
      of informativeness of (dC-dA)n.(dG-dT)n polymorphisms regardless of the repeat
      sequence category.

PMID- 1974879
TI  - Genetic mapping in the region of the mouse X-inactivation center.
AB  - The mouse X-inactivation center lies just distal to the T16H breakpoint.
      Utilizing pedigree analysis of backcross progeny from a Mus domesticus/Mus
      spretus interspecific cross, we have mapped a number of genetic loci, gene
      probes, microclones, and EagI linking clones distal to the T16H breakpoint. The
      genetic analysis provides a detailed genetic map in the vicinity of the mouse X
      inactivation center. Comparative mapping data from the human X chromosome
      indicate that the most probable location of the mouse X-inactivation center is
      distal to Ccg-1 and in the region of the Pgk-1 locus. We report the assignment of
      two new loci, EM13 and DXSmh44, to the Ccg-1/Pgk-1 interval.

PMID- 1974880
TI  - Accurate assessment of intragenic recombination frequency within the Duchenne
      muscular dystrophy gene.
AB  - Polymorphic loci that lie at the two extremities of the Duchenne/Becker muscular
      dystrophy (DMD/BMD) gene have been used to estimate intragenic recombination
      rates. Multipoint linkage analysis of the CEPH panel of families suggests a total
      intragenic recombination frequency of nearly 0.12 (confidence intervals 0.041
      0.226) over the genomic length of approximately 2 Mb.

PMID- 1974881
TI  - Pulsed-field gel analysis of alpha-satellite DNA at the human X chromosome
      centromere: high-frequency polymorphisms and array size estimate.
AB  - Using pulsed-field gel analysis (PFGE), we have characterized the large array of
      alpha-satellite DNA located in the centromeric region of the human X chromosome.
      The tandem repetitive nature of this DNA family lends itself to examination by
      PFGE using restriction enzymes that cleave frequently in unique sequence DNA but
      which cut only rarely within the repetitive alpha-satellite array. Several such
      restriction enzymes (BglI, BglII, KpnI, ScaI) have proven highly informative in
      sizing the alpha-satellite array and in following the segregation of individual X
      chromosome centromeres using PFGE polymorphisms. Among 29 different X
      chromosomes, alpha-satellite array length varied between 1380 and 3730 kb (mean =
      2895 kb; SD = 537). In three large CEPH families comprising 24 meioses,
      inheritance of these PFGE polymorphisms was strictly Mendelian, with no
      indication of intraarray recombination. Such DXZ1 alpha-satellite polymorphisms,
      therefore, may prove useful in the study of pericentromeric X-linked disorders.

PMID- 1974882
TI  - Genetic linkage of the human apolipoprotein AI-CIII-AIV gene cluster and the
      neural cell adhesion molecule (NCAM) gene.
AB  - The genes encoding apolipoproteins AI, CIII, and AIV, three plasma proteins
      involved in lipid metabolism, are clustered within a 15-kb DNA segment (apoAI
      CIII-AIV gene cluster) located on human chromosome 11 at band q23. The gene
      encoding the neural cell adhesion molecule (NCAM), a cell surface glycoprotein
      involved in cell-cell recognition during morphogenesis, is also located on
      chromosome 11, band q23. In this report, 12 previously described restriction
      fragment length polymorphisms (RFLPs) in the apoAI-CIII-AIV gene cluster were
      tested for cosegregation with a newly identified BamHI RFLP in the NCAM gene
      using 13 families. The results show that the apoAI-CIII-AIV gene cluster and the
      NCAM gene loci are linked with a maximum lod score of 15.9 at a recombination
      fraction of 0.028. In addition, an approach for the most efficient use of the
      apoAI-CIII-AIV gene cluster polymorphisms, based on the evaluation of their
      individual and cumulative heterozygosities, is presented.

PMID- 1974883
TI  - Photorespiratory ammonia assimilation in the leaves of barley, sorghum and
      Moricandia arvensis.
AB  - Effects of methionine sulphoximine (MSX) on glutamine synthetase activity and
      ammonia accumulation in the leaves of barley, sorghum and Moricandia arvensis
      were studied. Glutamine synthetase activity of sorghum leaves was relatively
      resistant to MSX treatment during initial stages. All the three plant species
      exhibited considerable accumulation of ammonia arising from non-photorespiratory
      sources, in response to MSX treatment. Minimal estimates of the rate of glycine
      decarboxylation were made employing MSX and isonicotinyl hydrazide together in
      the treatment solution. Changes in the pool sizes of amino acids involved in
      photorespiratory nitrogen metabolism as affected by MSX have also been
      investigated.

PMID- 1974884
TI  - Cross-reactive and strain-specific antipeptide antibodies to Pseudomonas
      aeruginosa PAK and PAO pili.
AB  - Antipeptide antibodies were raised against synthetic peptides corresponding to
      the amino acid sequences of eight surface predicted regions of the pilin proteins
      from Pseudomonas aeruginosa PAK and PAO. Four of the anti-PAK peptide antisera
      cross-reacted with strain PAO pili, while five anti-PAO peptide antisera cross
      reacted with strain PAK pili. Only one region of the two pilin proteins (region
      88-97) provided strain-specific antibodies when either strain PAK or strain PAO
      region 88-97 peptides were used to generate antipeptide antibodies. Our results
      clearly showed that cross-reactive and strain-specific antibodies cannot be based
      solely on the degree of homology in the aligned protein sequences. The majority
      of synthetic peptides bound to their homologous antipilus antiserum, suggesting
      that linear sequences play a significant role in the immunogenic response of
      native pili.

PMID- 1974885
TI  - Evidence that Candida stellatoidea type II is a mutant of Candida albicans that
      does not express sucrose-inhibitable alpha-glucosidase.
AB  - Candida stellatoidea is classically distinguished from C. albicans by the ability
      of the latter species to assimilate sucrose. We show here that sucrose-positive
      revertants of C. stellatoidea type II are readily isolated and that C.
      stellatoidea type II strains probably resulted from a mutation in the sucrase
      gene of C. albicans. The revertants were not laboratory contaminants, as
      determined by restriction fragment length polymorphism analysis and retention of
      an auxotrophic marker. The reversion of three tested strains was accompanied by
      16 to 110-fold increases in expression of a sucrase/alpha-glucosidase but not an
      invertase, with a Km for sucrose of about 1 mM. The enzyme activity was assayable
      in intact cells. The drastically increased expression of such an enzyme would
      allow extracellular sucrose hydrolysis and assimilation of the monosaccharide
      products.

PMID- 1974886
TI  - Survival and antigenic profile of irradiated malarial sporozoites in infected
      liver cells.
AB  - Exoerythrocytic (EE) stages of Plasmodium berghei derived from irradiated
      sporozoites were cultured in vitro in HepG2 cells. They synthesized several
      antigens, predominantly but not exclusively those expressed by normal early
      erythrocytic schizonts. After invasion, over half the intracellular sporozoites,
      both normal and irradiated, appeared to die. After 24 h, in marked contrast to
      the normal parasites, EE parasites derived from irradiated sporozoites continued
      to break open, shedding their antigens into the cytoplasm of the infected host
      cells. Increasing radiation dosage, which has previously been shown to reduce the
      ability of irradiated sporozoites to protect animals, correlated with reduced de
      novo antigen synthesis by EE parasites derived from irradiated sporozoites.

PMID- 1974888
TI  - Review: therapeutic concepts of congestive heart failure.
AB  - The therapeutic concepts of congestive heart failure (CHF) are based on an
      increase in myocardial contractility and a decrease in pre- and afterload.
      Besides the digitalis glycosides, diuretics and vasodilators such as nitrates,
      hydralazine, ACE-inhibitors, calcium antagonists or prazosine are used.
      Furthermore, the so-called inodilators such as phosphodiesterase III inhibitors
      (amrinone, milrinone), dopaminergic and beta-adrenergic receptor agonists were
      introduced into therapy. The boone and bane of the different classes of drugs
      were discussed with respect to their hemodynamic and clinical properties.

PMID- 1974887
TI  - Vibrio cholerae O395 tcpA pilin gene sequence and comparison of predicted protein
      structural features to those of type 4 pilins.
AB  - Vibrio cholerae O1 expresses a pilus that is coordinately regulated with cholera
      toxin production and hence termed TCP, for toxin-coregulated pilus. Insertion of
      Tn5 IS50L::phoA (TnphoA) into the major pilin subunit gene, tcpA, has previously
      been shown to render the strain avirulent as a result of its inability to
      colonize. One such insertion was isolated and used as a probe to screen for
      clones containing the intact tcpA gene. The DNA sequence of tcpA was determined
      by using the intact gene and several tcpA-phoA gene fusions. The deduced protein
      sequence agreed completely with that previously determined for the TcpA N
      terminus and with the size of the mature pilin protein. The reported homology
      with N-methylphenylalanine (type 4) pilins near the N terminus was extended and
      shown to include components of the atypical leader peptide as well as overall
      predicted structural similarities in other regions of the pilins. In contrast to
      the modified N-terminal phenylalanine residue found in all characterized type 4
      pilins, the corresponding position in tcpA contains a Met codon, thus implying
      that the previously uncharacterized amino acid corresponding to the N-terminal
      position of the mature TcpA pilin is a modified form of methionine. Except for
      this difference, mature TcpA has the overall predicted structural motifs shared
      among type 4 pilins.

PMID- 1974889
TI  - Age-associated functional impairments of specific neurotransmitter systems:
      detection by pharmacological brain metabolism studies and criteria for design of
      human investigations.
AB  - Although brain aging is accompanied by measurable deficits in cognitive and motor
      function, and frequently by selective loss of neurons, neurotransmitters and
      their receptors, resting brain energy metabolism, purported to reflect neural
      function, undergoes little or no quantitative change during aging in experimental
      animals or in man. A method is described for assessing the functional capacity of
      aging neurotransmitter systems in rats by measuring changes in regional cerebral
      metabolic rates for glucose in response to drug administration. Preliminary
      studies identified the pharmacokinetic and pharmacodynamic factors that determine
      cerebral metabolic responses to drugs, and established a relation between those
      responses and altered brain function. In awake, aged Fischer-344 rats, cerebral
      metabolic responses to the dopaminergic agents haloperidol and bromocriptine and
      to the serotonergic agonist m-chlorophenylpiperazine were reduced when compared
      to responses in young adult rats, despite similar or greater concentrations of
      drug in the brains of older animals. The metabolic response to arecoline, a
      muscarinic cholinergic agonist, was age-invariant. It was concluded that the
      cerebral metabolic response to drug administration is a useful measure of the
      functional capacity of neurotransmitter systems. Pharmacological brain metabolism
      studies demonstrated selective functional impairments in certain transmitter
      systems of the aged rat brain that were not detected by metabolic measurements in
      the resting state, nor predicted by changes in transmitter receptors. Specific
      criteria are proposed for pharmacological brain metabolism studies in man, using
      in vivo imaging, to identify functionally impaired neurotransmitter systems in
      aging and neurodegenerative diseases.

PMID- 1974890
TI  - Glutathione-dependent and ketone body-related enzymes in the selenium-deficient
      rat.
AB  - Male rats, born of selenium (Se)-depleted dams and continuously fed a Se
      deficient diet regimen or Se-repleted for 11 weeks, were used for some enzymatic
      determinations in samples from liver, heart, kidney and hind limb muscle. The Se
      dependent GSH-Px activity in liver and kidney of the Se-deficient group was less
      than 0.5% of Se-repleted controls, whereas a 3-fold increase in liver and kidney
      GSH S-transferase activity was found in these Se-deficient rats. The Se-deficient
      group excreted 3 times more acetoacetate via the urine than their Se-repleted
      siblings. The activity of the key enzymes of ketone body utilization was similar
      in tissues from Se-repleted and Se-deficient rats. It is suggested that
      longlasting or even Se-unresponsive changes in enzymes of ketone body metabolism
      might have developed in these rats born of Se-depleted dams.

PMID- 1974892
TI  - Fine mapping of a putative rd cDNA and its co-segregation with rd expression.
AB  - Retinal degeneration is inherited in an autosomal recessive pattern in the
      retinal degeneration (rd) mouse. The defective gene for this disease has been
      mapped to mouse chromosome 5 between the well-defined (anchor) genes Afp and Gus.
      We recently cloned a putative rd cDNA, zr.408, using a strategy based on
      subtractive and differential hybridization. zr.408 was shown to hybridize to a
      larger message from rd/rd mice than from normal mice in Northern blots; was
      mapped to mouse chromosome 5; and was used to detect restriction fragment length
      polymorphisms (RFLPs) between rd/rd and +/+ DNA in genomic Southern blots. In
      order to obtain further evidence that zr.408 does in fact correspond to the rd
      gene, we used two methods to position zr.408 on chromosome 5. Analysis of an
      intersubspecific backcross localized the sequences corresponding to zr.408
      between the genes Afp and Gus, as expected for rd. The second approach involved
      an interspecific backcross using C57BL/6J-rd/rd mice congenic for the normal
      allele of rd, which was derived from the wild mouse, Mus spretus; the results of
      this study showed that zr.408 is at or near the rd locus. These two studies add
      evidence to the existing data, which suggest that zr.408 is the correspondent of
      the rd gene.

PMID- 1974891
TI  - Analysis of genes coding for S-antigen, interstitial retinol binding protein, and
      the alpha-subunit of cone transducin in patients with retinitis pigmentosa.
AB  - We screened 526 unrelated patients with autosomal dominant, autosomal recessive,
      or simplex retinitis pigmentosa for evidence of mutations of the genes encoding S
      antigen (S-Ag), interstitial retinol binding protein (IRBP), and the alpha
      subunit of cone-specific transducin. Restriction fragment length polymorphisms
      (RFLPs) were identified at each of these loci. Within each set of patients with a
      particular genetic type of retinitis pigmentosa, RFLP alleles at each of these
      loci showed no departure from Hardy-Weinberg equilibrium. No gene deletions or
      rearrangements could be detected in any patient. Furthermore, in each of six
      pedigrees (one autosomal dominant, one autosomal recessive, three Usher's
      syndrome type I, and one Laurence-Moon-Bardet-Biedl syndrome) there was no co
      segregation of the disease with alleles determined by RFLPs at the locus for S
      antigen. At the IRBP locus, lack of co-segregation was seen in one autosomal
      dominant, two autosomal recessive, and three Usher's syndrome type I pedigrees.
      Finally, one pedigree with autosomal recessive retinitis pigmentosa showed no co
      segregation of the disease with alleles at the locus for the alpha-subunit of the
      cone-specific transducin. These data support the idea that the genes coding for S
      Ag, IRBP, and the alpha-subunit of the cone-specific transducin do not play an
      etiologic role in the families with retinitis pigmentosa so far studied.

PMID- 1974893
TI  - High-resolution sonography of the undescended testis in childhood: an analysis of
      45 cases.
AB  - A prospective study correlating the ultrasound and operative findings was carried
      out in 45 consecutive pediatric patients with undescended testes. Thirty-six of
      37 (97%) palpable testes were located preoperatively by ultrasound. Six of eight
      impalpable testes (75%) were correctly localized by ultrasound. The three testes
      missed by the ultrasound examination were found to be atrophic at surgery. Three
      intra-abdominal (palpable) testes were found at surgery just proximal to the
      internal ring; all three had been identified by ultrasound preoperatively. The
      main contribution of ultrasound was the preoperative detection of impalpable
      testes (six of eight), which modified the consequent surgical approach.
      Ultrasound also helped in providing objective support to the clinical diagnosis
      in 36 of 37 children with palpable undescended testes. The ultrasound examination
      is noninvasive, nonionizing, readily available and of low cost. It is therefore
      suitable as the initial routine procedure for the evaluation of undescended
      testis.

PMID- 1974894
TI  - Interhemispheric empyema. An unusual form of subdural empyema.

PMID- 1974895
TI  - DL-3,3-difluoroglutamate: an enhancer of folylpolyglutamate elongation.
AB  - The effect of 3,3-difluoroglutamate (F2Glu) on the reaction catalyzed by rat
      liver folypolyglutamate synthetase was investigated. F2Glu was a potent,
      concentration-dependent inhibitor of poly(gamma-glutamylation) using [3H]Glu and
      either methotrexate (4-NH2-10-CH3PteGlu) or tetrahydrofolate as substrates. It
      was determined that F2Glu acted as an alternate substrate, but in contrast to the
      previously characterized alternate substrate 4-fluoroglutamate (McGuire, J.J.,
      and Coward, J.K. (1985) J. Biol. Chem. 260, 6747-6754), it did not terminate
      polyglutamate chain elongation. Instead, F2Glu promoted chain elongation. Thus,
      synthesis of products from [3H]methotrexate containing 1 and 2 additional amino
      acid residues occurred at a substantially higher rate in the presence of F2Glu
      when compared to identical reactions in the presence of Glu; this was more
      pronounced for the product containing 2 additional residues. Identities of the
      products were established by their respective chromatographic elution positions
      and by limit digestion with gamma-glutamyl hydrolases. Ligation of Glu to 4-NH2
      10-CH3PteGlu-gamma-(3,3-difluoroglutamate) was also enhanced. These results are
      consistent with F2Glu enhancing the synthesis of poly(gamma-glutamate)
      metabolites at the level of either the incoming amino acid (glutamate analog) or
      the gamma-glutamyl acceptor species. F2Glu is thus the first glutamate analog
      which enhances chain elongation catalyzed by folypolyglutamate synthetase.

PMID- 1974896
TI  - DNA helicase from calf thymus. Purification to apparent homogeneity and
      biochemical characterization of the enzyme.
AB  - We have purified a DNA helicase from calf thymus to apparent homogeneity by
      monitoring the activity with a strand displacement assay. DNA helicase followed
      the DNA polymerase alpha-primase complex through chromatography on
      phosphocellulose and hydroxylapatite. Separation from DNA polymerase alpha
      primase complex as well as from the bulk of another DNA-dependent ATPase was
      achieved on heparin-Sepharose. Further purification steps included ATP-agarose
      and fast protein liquid chromatography-Mono S. A 47-kDa polypeptide cosedimented
      with the DNA helicase activity in a glycerol gradient as well as in gel
      filtration on Superose 6. The calf thymus DNA helicase had a sedimentation
      coefficient of 4-7 S and Stokes radius of about 45 A suggesting that the enzyme
      might be monomer in its functional form. DNA helicase activity requires a
      divalent cation with Mg2+ being more efficient than Mn2+ or Ca2+. Hydrolysis of
      ATP is required since the two nonhydrolyzable ATP analogs adenosine 5'-O-(3
      thiotriphosphate) and adenylyl (beta, gamma-methylene)diphosphonate cannot
      substitute for ATP or dATP in the displacement reaction. Calf thymus DNA helicase
      is able to use ATP, dATP, dideoxy-ATP, CTP, and dCTP with Km for ATP and dATP of
      0.2 and 0.25 mM, respectively. The enzyme can displace a fragment of 24 bases
      completely in an enzyme concentration- and time-dependent manner. The DNA
      helicase appears to bind to single-stranded DNA and to move to single-strand
      double-strand transition. The directionality of unwinding is 3'----5' with
      respect to the single-stranded DNA to which the enzyme is bound.

PMID- 1974897
TI  - Perturbation of intestinal microvillar enzyme biosynthesis by amino acid analogs.
      Evidence that dimerization is required for the transport of aminopeptidase N out
      of the endoplasmic reticulum.
AB  - The amino acid analogs canavanine, 3-hydroxynorvaline, thialysine, 6
      fluorotryptophan, m-fluorotyrosine, and 2-fluorophenylalanine were incorporated
      into proteins, synthesized in pig intestinal mucosal explants, and their effect
      on molecular processing and intracellular transport of microvillar enzymes
      studied. Unless they were used in combination, none of the analogs drastically
      reduced the expression of aminopeptidase N (EC 3.4.11.2) or sucrase-isomaltase
      (EC 3.2.1.48, EC 3.2.1.10), but to a varying extent, they all slowed the rate of
      transport to the apical surface. In contrast, the cellular export of a secretory
      protein, apolipoprotein A-1, was largely unaffected. For the microvillar enzymes,
      all six analogs caused an accumulation of the transient, high mannose
      glycosylated form, indicating an analog-sensitive stage prior to the Golgi
      associated processing. For aminopeptidase N, this arrest was shown to correlate
      with a reduced ability of its transient high mannose-glycosylated form to form
      homodimers as judged from cross-linking experiments, suggesting dimerization to
      be obligatory for transport out of the endoplasmic reticulum.

PMID- 1974898
TI  - High-performance liquid chromatographic method for the determination of carazolol
      in serum or plasma of pigs.

PMID- 1974899
TI  - The congenital long QT syndromes in childhood.
AB  - Twenty-three children and young persons with a congenital long QT syndrome were
      identified; the median age at the time of referral was 10 years (range 4 days to
      19 years) and 14 patients (61%) had a family history of the syndrome. Among the
      19 patients with symptoms, the initial symptom was syncope in 13 (69%), aborted
      sudden death in 5 (26%) and near drowning in 1 (5%). There were three deaths
      during a combined follow-up period of 67 patient-years (average annual mortality
      rate 4.5%). Patients who did not respond to therapy with a beta-adrenergic
      blocker and those who died were significantly younger than the remaining patients
      at the time of diagnosis (p less than or equal to 0.05 for both). Analysis of 44
      treadmill exercise tests performed by 16 patients revealed significant
      prolongation of the median corrected QT (QTc) interval in response to exercise,
      with maximal prolongation present after 2 min of recovery (median QTc interval
      0.52 s versus a baseline value of 0.47 s, p less than 0.001). Characteristic
      changes in T wave configuration were noted in 8 of 15 patients on at least one
      occasion during ambulatory Holter electrocardiographic monitoring, including T
      wave alternation in two patients, both of whom died shortly afterward. It is
      suggested that the congenital long QT syndrome is associated with a significant
      mortality rate in childhood despite the use of conventional therapy in
      symptomatic patients. Ambulatory Holter monitoring and treadmill exercise testing
      may be helpful, both in confirming the diagnosis of a long QT syndrome and in
      monitoring the adequacy of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1974900
TI  - Expression of the multidrug resistance gene product (P-glycoprotein) in human
      normal and tumor tissues.
AB  - We have characterized the normal human tissue distribution and tumor expression
      of the human multidrug resistance gene (MDR1) product P-glycoprotein (Pgp) by
      immunohistochemical staining of frozen tissue sections of human normal and tumor
      tissues, using three mouse monoclonal antibodies (MAb) which recognize at least
      two different epitopes of Pgp. Pgp expression on normal human tissues was
      detected in specialized epithelial cells with secretory/excretory functions,
      trophoblasts in the placenta, and on endothelial cells of capillary blood vessels
      at blood-tissue barrier sites. There were significant differences in the staining
      patterns of these MAb. Mouse MAb HYB-241 and HYB-612 each recognize an
      extracellular epitope of Pgp, whereas mouse MAb C219 detects a carboxy terminal
      intracellular epitope and has recently been reported to crossreact with the MDR3
      gene product. HYB-241 and HYB-612 strongly stain endothelial cells and
      trophoblasts, whereas C219 is weakly positive or unreactive on these cells.
      Likewise, C219 strongly stains the biliary pole of hepatocytes, skeletal and
      heart muscle fibers, whereas HYB-241 and HYB-612 are unreactive on these cells.
      Immunopathological studies were performed on a wide variety of human tumors. Pgp
      expression on human tumors was most commonly detected in colon. renal, and
      adrenal carcinomas; rarely in lung and gastric carcinomas and certain germ cell
      tumors; and was undetectable in breast and endometrial carcinomas tested. Few
      sarcomas and none of the melanomas, neuroblastomas, gliomas, and
      pheochromocytomas had detectable Pgp expression. Intensity and pattern of
      staining varied among different cases of a given tumor type; although homogeneous
      immunoreactivity was observed, heterogeneity of expression in a single
      histological section was more common. The finding of Pgp expression in a variety
      of normal tissues with diverse physiological functions suggests that the role of
      Pgp may not be limited to excretion of xenobiotics. Pgp expression in capillaries
      of the brain and testis may explain the failure of drugs such as vincristine and
      actinomycin-D to penetrate into these tissues, allowing them to remain as
      pharmacological sanctuaries for malignant cells. Although Pgp expression can now
      be detected in a variety of human tumors, further studies are needed to establish
      the possible significance of this finding.

PMID- 1974901
TI  - D-aspartate oxidation by rat and bovine renal peroxisomes: an electron
      microscopic cytochemical study.
AB  - D-amino acid oxidase, a peroxisomal enzyme, and D-aspartate oxidase, a potential
      peroxisomal enzyme, share biochemical attributes. Both produce hydrogen peroxide
      in flavin-requiring oxidative reactions. Such similarities suggest that D
      aspartate oxidase may also be localized to peroxisomes. Definitive identification
      of D-aspartate oxidase as a peroxisomal enzyme depends, however, on visualization
      at the electron microscopic level. Using incubation conditions shown to be
      specific for the enzyme in biochemical studies, this report extends the
      cytochemical localization of D-amino acid oxidase to bovine renal peroxisomes,
      and shows that D-aspartate can be oxidized by rat and bovine renal peroxisomes.
      An unexpected finding was the sensitivity of both D-amino acid oxidase activity
      (proline specific) and D-aspartate oxidase activity to inhibition by agents used
      in biochemical studies to discriminate between the two enzyme activities.
      Therefore, it is possible that, in the cytochemical system used in this study,
      (a) either D-proline and D-aspartate are substrates for only one enzyme or (b)
      the two enzymes have additional overlapping biochemical properties.

PMID- 1974902
TI  - The efficacy of control measures for eradicating legionellae in showers.
AB  - The efficacy of secondary control measures on showers colonized with legionellae
      was assessed. Hyperchlorination of shower heads and angle valve strainers had
      only a short-lived effect on legionellae. Automatic drain valves fitted to
      showers were ineffective in maintaining a reduction in the number of legionellae
      in shower water. Regular flushing of showers reduced legionellae to below
      detectable levels. Removal of dead-legs from the feed-pipes supplying hot water
      to showers, resulted in a decrease in legionellae in these sites but an increase
      in legionellae colonizing mixer valve components.

PMID- 1974903
TI  - Skin sampling-validation of a pad method and comparison with commonly used
      methods.
AB  - Two types of pad were tested for sampling bacteria from the skin. One pad was
      made of 85% viscose and a 15% mixture of polyester and polyamide fibres, the
      other was made of polyvinyl-alcohol foam. The efficiency was calculated using
      double samples and 8 consecutive samples. The two pads were equally efficient and
      more efficient when moist. Their efficiency was compared with that of the bud
      swab, the Rodac plate and the scrub cylinder method. Using the double sample
      method for calculation, the scrub cylinder method and the pads were equally
      efficient, around 50%. As calculated from consecutive samples the efficiency of
      the pads was about 45%, the efficiency of the cylinder scrub method 29%, and that
      of the bud swab and Rodac plate 16% and 5% respectively. The low efficiency of
      the Rodac plate may be partly explained by the fact that microcolonies and not
      bacterial cells are sampled with this method.

PMID- 1974904
TI  - A microbiologist's view of commissioning operating theatres.
AB  - We report our experiences of microbiological testing of operating theatres over a
      10-year period. Major faults within the theatres can be detected by
      microbiological monitoring of air flow direction and the bioload in theatre air.
      We advocate that there should be a close cooperation between the microbiologist
      and the hospital engineering department for effective monitoring of theatre
      commissioning and upgrading. Also we recommend that contract work should be
      closely supervised particularly with respect to theatre ventilation systems.

PMID- 1974905
TI  - A survey of methicillin-resistant Staphylococcus aureus affecting patients in
      England and Wales.
AB  - For a six-month period between October 1987 and March 1988, 660 isolates of
      methicillin-resistant Staphylococcus aureus (MRSA) from 570 patients were sent to
      the Staphylococcus Reference Laboratory at Colindale to supplement the National
      reporting survey of MRSA in England and Wales. The isolates were characterized by
      phage typing, antibiotic susceptibility and by selected biochemical tests.
      Patient details were also surveyed. Fourteen strains affected more than one
      hospital and were called multi-hospital epidemic strains. One strain, EMRSA-1,
      accounted for more than 40% of isolates and of patients. Other epidemic strains
      were defined. Ten additional strains were restricted to single hospitals. Only 25
      primary isolates were non-typable but 67 sporadic typable strains occurred. The
      patients affected were approximately equally either infected or colonized. The
      sexes were represented equally. Orthopaedic and geriatric wards were over
      represented. Epidemic strains were clumping factor positive while some sporadic
      strains were weak producers. Urea alkalinization and protein A production could
      supplement phage typing and antibiotic resistance in strain recognition.

PMID- 1974906
TI  - A study of the relationships between antibiotic resistance phenotypes, phage
      typing and biotyping of 117 clinical isolates of Acinetobacter spp.
AB  - Two typing systems were used to conduct an epidemiological study of Acinetobacter
      and to establish their relationship to antibiotic resistance phenotypes.
      Biotyping was performed with biochemical tests according to the new definition of
      Acinetobacter baumannii (18 biotypes). Phage typing included two complementary
      systems: 125 phage-types and 25 subtypes. Resistance phenotype analysis included
      11 antibiotics. The results of the study showed that: (1) nine phage-types or
      subtypes (67%) and two groups of atypical phage-types (5%) or of untypable
      strains (28%), could be defined; (2) all strains that were resistant to
      carboxy/ureido-penicillins and cephalosporins (62%) belonged to biotypes 6 or 9;
      among them 70% belonged to phage-types 17 or 124; (3) imipenem resistance was
      observed in five isolates of biotype 9 and one of biotype 6; (4) a phenotype
      including resistance to third generation cephalosporins (but not
      carboxypenicillins) and to amikacin (but not tobramycin) represented 8.5% of the
      isolates; 90% of them belonged to biotype 1 and were not phage-typable; (5) 15%
      of the isolates were not identified as A. baumannii; among them five
      Acinetobacter haemolyticus strains all had the same resistance phenotype:
      amikacin-tobramycin-kanamycin-netilmicin resistant; they were however,
      susceptible to beta-lactams and to gentamicin. There was a clear relationship
      between biotypes 6 and 9 and phage-types 17 and 124 which were the strains most
      resistant to beta-lactams and aminoglycosides and were predominant in the survey.
      The three typing systems were complementary but it seems that antibiotic
      resistance phenotypes and one of the two other typing systems would be required
      in parallel to provide suitable information for epidemiological purposes.

PMID- 1974907
TI  - A pseudo-outbreak of Pseudomonas on a special care baby unit.
AB  - Following isolation of a multi-antibiotic-resistant pseudomonad from a newborn
      infant on admission to the Special Care Baby Unit and further isolation of
      apparently the same organism from two additional infants, a full investigation
      was instigated in an attempt to discover the source of the organism. This
      revealed a further 13 infants apparently colonized with the same organism.
      Repeated screening of the infants with a commercial sterile swab/transport medium
      failed to isolate the organism. Examination of bottles of the in-house transport
      medium, which had been stored under a sink, produced further isolates of the same
      organism. Water splashed from the sink was suspected as the ultimate source of
      contamination. Biochemical characterization showed that P. pickettii and at least
      one other Pseudomonas species were involved. The epidemiological, clinical and
      economic implications of the 'outbreak' are discussed together with the ultimate
      financial implications for investigation of such incidents.

PMID- 1974908
TI  - Micrococcus and Stomatococcus spp. from human infections.
AB  - Infections with Micrococcus spp. in six patients and Stomatococcus mucilaginosus
      in one patient are described. Two of the Micrococcus infections occurred in
      leukaemic patients with indwelling lines, six episodes occurred in three patients
      undergoing continuous ambulatory peritoneal dialysis and one occurred in a
      patient with a ventriculo-peritoneal shunt. Stomatococcus was isolated from fluid
      draining from a sub-dural haematoma. Colony morphology, oxidase reaction and
      resistance to nitrofuration were useful in differentiation of micrococci from
      staphylococci. Incidence and risk factors for micrococcal infections appear
      similar to those for infections with coagulase-negative staphylococci (CNS), but
      the literature is confused due to changes in the definitions of these genera.

PMID- 1974909
TI  - False-positive gram-stained smears of sterile body fluids due to contamination of
      laboratory deionized water.
AB  - Bacterial contamination of staining reagents led to false-positive smears from
      clinical samples. Piped deionized water used to make up the staining reagents was
      found to be the source of contamination. The closed loop system supplying the
      deionized water was decontaminated with hydrogen peroxide and upgraded by
      addition of a reverse osmosis unit and bacterial filter. No subsequent
      contamination has been demonstrated.

PMID- 1974910
TI  - Infection of staff during an outbreak of viral gastroenteritis in an elderly
      persons' home.
AB  - An outbreak of viral gastroenteritis in an elderly persons' residence is
      reported. Seventeen of 37 (47%) residents and 22 of 50 (44%) staff developed
      illness. Adenovirus was seen by direct electron microscopy in two vomitus and two
      faeces specimens. It is suggested that the most likely mode of transmission was
      environmental contamination by vomitus.

PMID- 1974911
TI  - Living with EMRSA-1.

PMID- 1974912
TI  - The efficacy of chlorination and filtration in the control and eradication of
      Legionella from dental chair water systems.
AB  - The apparent failure of hyperchlorination and continuous dosing with chlorine to
      eliminate legionellae from a dental teaching hospital water supply prompted a
      prospective study to evaluate charcoal filters as a means of decontamination.
      Legionella pneumophila serogroup 10 and L. bozemanii serogroup 2 were isolated
      from dental units yielding 10(1)-10(3) colony forming units (cfu) ml-1 with total
      bacterial counts in the range 10(2)-greater than 10(4) cfu ml-1. After chair-side
      installation of charcoal filters bacterial contamination of the dental unit water
      was prevented and legionellae were initially not detected, but after 7 days the
      total count returned to pre-filtration levels of greater than 10(4) cfu ml-1; L.
      pneumophila serogroup 10 was eliminated but L. bozemanii serogroup 2 persisted.
      These results suggest that neither chlorination nor charcoal filtration deal
      adequately with the potential hazard of Legionella spp. in dental water.

PMID- 1974913
TI  - Quantitative analysis of the immunocompetent cells in periapical granuloma:
      correlation with the histological characteristics of the lesions.
AB  - Granuloma formation includes an immune response in oral tissues to various
      microorganisms and their products. The immunocompetent cells of both series (T
      and B) are present in the periapical lesions. In order to further analyze the
      relative contribution and pathophysiological significance of the T cell subsets
      in granuloma formation, we undertook the quantitative analysis of the CD3
      positive, CD4-positive, CD8-positive and Ig-positive cells in these lesions by
      using indirect immunofluorescence. Evidence is provided showing predominance of T
      cells in diffuse and B cells in focal mononuclear infiltrates. CD8-positive cells
      were more frequent in diffuse infiltrates and in particular in granulomas with
      distinct epithelium while CD4-positive cells were more numerous in focal
      infiltrates. It appears that the presence and ratios of different subsets of
      immunocompetent cells reflects the pathogenesis of granuloma and transformation
      to cyst.

PMID- 1974914
TI  - Expression of human adenosine deaminase in mice transplanted with hemopoietic
      stem cells infected with amphotropic retroviruses.
AB  - Amphotropic recombinant retroviruses were generated carrying sequences encoding
      human adenosine deaminase (ADA). Transcription of the human ADA gene was under
      control of a hybrid long terminal repeat in which the enhancer from the Moloney
      murine leukemia virus was replaced by an enhancer from the F101 host-range mutant
      of polyoma virus. Hemopoietic stem cells in murine bone marrow were infected with
      this virus under defined culture conditions. As a result, 59% of day-12 colony
      forming unit spleen (CFU-S) stem cells became infected without any in vitro
      selection. Infected CFU-S were shown to express human ADA before transplantation
      and this expression sustained upon in vivo maturation. Mice transplanted with
      infected bone marrow exhibited human ADA expression in lymphoid, myeloid, and
      erythroid cell types. Moreover, human ADA expression persisted in secondary and
      tertiary transplanted recipients showing that human ADA-expressing cells were
      derived from pluripotent stem cells. These characteristics of our amphotropic
      viruses make them promising tools in gene therapy protocols for the treatment of
      severe combined immunodeficiency caused by ADA deficiency. In this respect it is
      also relevant that the viral vector that served as backbone for the ADA vector
      was previously shown to be nonleukemogenic.

PMID- 1974915
TI  - The pili of Aeromonas hydrophila: identification of an environmentally regulated
      "mini pilin".
AB  - Ultrastructural studies of Aeromonas hydrophila strain AH26 revealed two
      distinctive pilus types: "straight" pili appear as brittle, rod-like filaments,
      whereas "flexible" pili are supple and curvilinear. Straight pili are produced
      constitutively under all tested conditions of growth. In contrast, the expression
      of flexible pili is regulated by physical and chemical variables, being produced
      at 22 vs. 37 degrees C, in a liquid vs. a solid medium, and when the availability
      of free-iron is reduced by the presence of deferoxamine mesylate. Both pilus
      proteins were purified and biochemically and functionally characterized. The
      major repeating subunit of the straight pilus is a 17,000-mol wt polypeptide with
      amino acid sequence homology with Escherichia coli type 1 and Pap pili. The
      flexible pilus filament is a homopolymer composed of a novel 46 amino acid
      polypeptide. Resistance of the flexible pilus filament to disaggregation using
      various chemical treatments was demonstrated; its stability as a polymer and its
      apparent mechanical strength seem to be conferred by a 20 amino acid hydrophobic,
      COOH-terminal domain. Purified straight pili lack hemagglutinating function. In
      contrast, purified flexible pili cause the agglutinin of human, guinea pig,
      ovine, bovine, and avian erythrocytes, although this property could only be
      demonstrated in the presence of divalent cations and was most evident at 4 vs. 22
      degrees C. Taken together, these results suggest that the pathogenic and
      ecological roles of the flexible pilus are related to this species' existence as
      a free-living organism in aquatic environments and its ability to cause
      infections, both in cold-blooded vertebrates and the human intestine.

PMID- 1974917
TI  - A reevaluation of excitatory amino acid-mediated synaptic transmission in rat
      dentate gyrus.
AB  - 1. Intracellular recordings were made from granule cells in combined slices of
      the hippocampus and parahippocampal cortex from adult Wistar rats. The neurons
      had a mean resting membrane potential (EM) of -85.1 +/- 0.7 (SE) mV, input
      resistance (Rin) of 30.9 +/- 1.5 M omega and action potential (AP) amplitude of
      79.9 +/- 1.06 mV measured from the threshold potential. The threshold for AP
      generation was approximately 40 mV positive to EM. 2. The passive current-voltage
      relationship showed anomalous rectification, with Rin increasing by 34% on
      average at modest depolarizations. With large excursions of the EM (by +/- 30 mV
      or more), there was a marked fall in Rin. 3. With extracellular recording, a
      monophasic, positive-going field potential of 5-15 mV was evoked by stimulation
      of the perforant path (PP). Intracellularly, an excitatory postsynaptic potential
      (EPSP) of up to 40 mV in size was recorded. It was unusual to evoke an AP on
      orthodromic stimulation. Perfusion with picrotoxin (PTX, up to 20 microM) had
      small and variable effects on the EPSP, which implies that GABAergic inhibition
      does not play a major role. 4. Tonic depolarization reduced the EPSP.
      Hyperpolarization either had no effect or again decreased the EPSP. 5. The role
      of excitatory amino acid (EAA) receptor subtypes in mediation of the EPSP was
      investigated. Perfusion with the non-N-methyl-D-aspartate (NMDA) receptor
      antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) caused a dose-dependent
      reduction of the EPSP with a shift to the right of the input-output relationship.
      The ED50 for this effect was approximately 2 microM. 6. In the presence of 5-10
      microM CNQX a small component of the EPSP usually remained, which could be
      blocked by the NMDA receptor antagonist +/- 2-amino-5-phosphonovaleric acid (APV,
      20-50 microM). This depolarizing component was markedly enhanced during perfusion
      with Mg2(+)-free medium. It increased in size and duration when the membrane was
      depolarized and decreased with hyperpolarization. These properties are consistent
      with the mediation of this potential via NMDA receptors. 7. These results
      indicate that NMDA receptors contribute to transmission at the synapse between
      the PP and the granule cell. This was confirmed by demonstrating that APV caused
      a small reduction in the size of the untreated EPSP and a shortening of the
      recovery phase.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1974916
TI  - Natural autoantibodies to thymocytes: origin, VH genes, fine specificities, and
      the role of Thy-1 glycoprotein.
AB  - 15 SM/J mouse hybridoma antibodies that show antithymocyte autoantibody (ATA)
      activity by immunofluorescence staining were studied. Half of these antibodies
      react with determinants whose expression is associated with Thy-1, as shown by
      blocking experiments with anti-Thy-1 and loss of reactivity with Thy-1- mutant
      cell lines. The Thy-1 dependence of three of these ATA is further confirmed by
      their reexpression on a Thy-1 gene transfectant. However, the remaining
      antibodies exhibited binding that showed little or no dependence on Thy-1.
      Furthermore, we find that most ATA derives from the Ly-1 B subpopulation, as
      demonstrated by lipopolysaccharide-induced ATA secretion in vitro and by
      comparison of ATA hybridoma frequencies. VH region gene sequence data of 14
      monoclonal ATA from Ly-1 B cell-derived hybridomas reveal the utilization of nine
      VH genes belonging to four different VH families (J558, 3609, Q52, and Vgam3.8).
      While we find that two of these hybridomas arose from a clonal expansion, we also
      find four examples of a 3609 family VH gene utilized in clonally independent
      lines showing similar specificity. Yet another example of identical VH gene usage
      by clonally unrelated cells is found in two J558 ATA of a distinct fine
      specificity. These data suggest that the enrichment of ATA B cells in the Ly-1 B
      subset is primarily due to repeated independent recruitment of B cells by antigen
      resulting in the expression of a restricted set of VH genes.

PMID- 1974918
TI  - Cerebral hypoxia: some new approaches and unanswered questions.

PMID- 1974919
TI  - Electroconvulsive shock differentially increases binding to alpha-1 adrenergic
      receptor subtypes in discrete regions of rat brain.
AB  - Quantitative in vitro autoradiographic methods were used to examine for the
      effect of repeated administration of electroconvulsive shock (ECS) on binding to
      subtypes of the alpha-1 receptor in rat brain. Rats were treated once daily for
      10 d with ECS or sham ECS, then killed, and brains were removed and sectioned for
      autoradiographic analysis. Total alpha-1 binding (including both alpha-1a and
      alpha-1b subtypes) was assessed with [3H]prazosin; alpha-1b binding was assessed
      with [3H]prazosin in the presence of 10 nM WB4 101 to mask alpha-1a binding; and
      alpha-1a binding was assessed with [3H]WB4 101. ECS caused a significant increase
      in [3H]prazosin binding in most cortical regions: this increase was confined to a
      band corresponding to cortical laminae I-III. Subtype analysis indicated that the
      increase in cortical binding was due to an increase in binding to the alpha-1b
      subtype. Dense alpha-1 binding was detected in most thalamic nuclei: however,
      only 1 small area, the parafascicular nucleus, showed a significant increase in
      alpha-1 binding following repeated ECS. The only other region where ECS was shown
      to significantly affect alpha-1 binding was the amygdala. Binding to all regions
      of the amygdala except the central nuclei was increased by ECS: in the lateral
      amygdala, this was due primarily to an increase in alpha-1b binding, while in the
      remaining regions the increase was primarily an alpha-1a phenomenon. Thus the
      effect of repeated ECS on alpha-1 binding in rat brain was found to be confined
      to several specific regions of the cortex, thalamus, and amygdala. Furthermore,
      in each of these regions, the ECS effect was limited to 1 or the other of the 2
      subtypes of the alpha-1 receptor.

PMID- 1974920
TI  - Identification of MARPP-58, a morphine- and cyclic AMP-regulated phosphoprotein
      of 58 kDa, as tyrosine hydroxylase: evidence for regulation of its expression by
      chronic morphine in the rat locus coeruleus.
AB  - Previously, we have identified a number of morphine- and cyclic AMP-regulated
      phosphoproteins (MARPPs) in the rat locus coeruleus (LC) and other brain regions.
      We now show that one of these phosphoproteins, a 58 kDa protein designated MARPP
      58, is tyrosine hydroxylase. First, MARPP-58 comigrates with immunolabeled,
      immunoprecipitated, and purified tyrosine hydroxylase on 1- and 2-dimensional
      electrophoresis. Second, MARPP-58, immunoprecipitated tyrosine hydroxylase, and
      purified tyrosine hydroxylase yield identical 1-dimensional phosphopeptide maps.
      Third, MARPP-58 exhibits a regional and subcellular distribution in brain
      consistent with tyrosine hydroxylase. Identification of MARPP-58 as tyrosine
      hydroxylase made it possible to determine whether increases in MARPP-58
      phosphorylation induced by chronic morphine in the LC reported previously are
      associated with alterations in enzyme activity and expression in this brain
      region. We show that chronic treatment of rats with morphine increases levels of
      tyrosine hydroxylase activity, immunoreactivity, and mRNA in the LC. Induction of
      the enzyme by chronic morphine was blocked by concomitant treatment of rats with
      the opiate receptor antagonist naltrexone, indicating that morphine produces this
      effect through the activation of opiate receptors. Consistent with previous
      observations that the chronic morphine-induced change in MARPP-58 phosphorylation
      is specific to the LC, changes observed in enzyme activity, immunoreactivity, and
      mRNA were not observed in a number of other brain regions studied. The results
      indicate that chronic morphine regulates the expression of tyrosine hydroxylase
      specifically in the LC and suggest that such regulation reflects long-term
      adaptations of LC neurons to chronic morphine at the level of gene expression.

PMID- 1974921
TI  - Pattern of expression of gamma-glutamyl transpeptidase in rat liver and kidney
      during development: study by immunochemistry and in situ hybridization.
AB  - We used an in situ hybridization technique using single-stranded RNA probes to
      study the expression pattern of gamma-glutamyl transpeptidase (GGT) in rat liver
      and kidney during development. The results were compared to those obtained with
      an immunoperoxidase technique and with Northern blot analysis of GGT mRNA. In the
      kidney, northern blot revealed a 20-fold increase of GGT mRNA between day 18 of
      gestation and adulthood. Protein and mRNA localization clearly identified the
      proximal tubules as the site of synthesis of GGT. In the liver, the expression
      was lower than in the kidney and Northern blot showed a dramatic decrease of
      expression after birth. Using immunohistochemistry, the protein was detected
      within parenchymal cells in embryo and hepatocyte membranes and bile ducts in
      adults. Using in situ hybridization, GGT mRNA was only detected on days 1 and 2
      after birth and exclusively in hepatocytes. Immunoperoxidase may be more
      sensitive than in situ hybridization to study the expression of minor liver
      protein such as GGT. However, the study of GGT expression using in situ
      hybridization is possible in cases of increased expression such as alcoholism,
      cholestasis, and carcinogenesis.

PMID- 1974922
TI  - Alpha-adrenergic modulation of the transient outward current in rabbit atrial
      myocytes.
AB  - 1. A whole-cell voltage-clamp technique has been used to study the alpha-effects
      of the adrenergic agonists noradrenaline, methoxamine and phenylephrine on the
      action potentials and membrane currents of rabbit atrial myocytes. Experiments
      were carried out at 22-23 degrees C. 2. In the presence of 10(-6) M-propranolol,
      all three agents prolonged action potential duration. This change could be
      ascribed principally to changes in membrane current early during the plateau
      phase of the action potential. In the presence of 10(-3) M-4-aminopyridine, no
      changes in calcium current (ICa) were observed on exposure to alpha-agonists. No
      significant shift in the voltage dependence or change in the amplitude of the
      calcium current-voltage relation was observed. 3. Exposure to 3 x 10(-4) M-CdCl2
      to block ICa reduced the action potential prolongation caused by alpha-adrenergic
      agonists. Measurement of unloaded cell shortening revealed that action potential
      prolongation caused by alpha-agonists, especially at low stimulus rates, could
      contribute significantly to the positive inotropic effect of alpha-adrenoceptor
      stimulation. 4. The voltage-activated transient outward current (It) was markedly
      reduced during exposure to alpha-adrenergic agonists in a dose-dependent manner
      in the presence of CdCl2 (3 x 10(-4) M) and propranolol in sufficient
      concentration to prevent beta-adrenoceptor activation. Noradrenaline exhibited a
      higher potency for this effect than either methoxamine or phenylephrine. The
      noradrenaline concentration required to give 50% of the maximal effect was 6 x
      10(-6) M compared with 2.3 x 10(-4) M for methoxamine. Noradrenaline reduced It
      by only about 60% of the maximum reduction produced by methoxamine suggesting
      that it could be classified as a partial agonist for this effect. 5. The
      reduction of It during exposure to alpha-adrenergic agonists was rate dependent
      in that larger current reductions were observed at very low rates of stimulation
      (less than 0.1 Hz). 6. The magnitudes of current-voltage relations for It were
      reduced over the entire voltage range studied during exposure to alpha-adrenergic
      agonists and reductions were dose dependent. No shift of these relations along
      the voltage axis was observed. 7. The steady-state inactivation relations for It
      were studied using two voltage clamp protocols. A two-step method resulted in a
      relatively steep sigmoid 'quasi-steady-state' relation. The half-inactivation
      potential of -27 mV was unaffected by alpha-adrenergic agonists.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 1974924
TI  - Responses of blood vessels in the rabbit knee to electrical stimulation of the
      joint capsule.
AB  - 1. An in vitro preparation of the rabbit knee joint, perfused with oxygenated
      Locke's solution, was used to study the response of articular blood vessels to
      electrical stimulation of the joint capsule. 2. Using trains of stimulus pulses
      of different durations, frequency-response curves were obtained. Electrical
      stimulation always produced vasoconstriction of joint blood vessels, which
      increased as a function of both frequency and pulse width. 3. This
      vasoconstrictor response was neurally mediated as it was markedly inhibited after
      addition to both bath and perfusate of tetrodotoxin. In addition, the response to
      field stimulation of the capsule was virtually abolished in animals pretreated
      with reserpine which depletes sympathetic nerve endings of noradrenaline. 4. The
      response to electrical stimulation was substantially reduced by the alpha
      adrenergic antagonist phenoxybenzamine (10(-5) M), the alpha 1-blocker prazosin
      (10(-6) M), and by guanethidine (10(-5) M) which inhibits the release of
      noradrenaline, ATP and neuropeptide Y from sympathetic nerve endings. 5. The
      attenuation of the vasoconstrictor response to field stimulation by prazosin (10(
      6) M) was little altered by addition of the alpha 2-adrenoceptor blocker
      rauwolscine (10(-6) M) to the perfusate. 6. alpha, beta-Methylene ATP (10(-6) M),
      a P2-purinoceptor desensitizer, had no effect on the vasoconstrictor response to
      electrical stimulation. 7. These results indicate that the vasoconstrictor
      response to electrical stimulation of the rabbit knee joint capsule is mediated
      via noradrenaline acting upon alpha 1-adrenoceptors.

PMID- 1974923
TI  - Development of L-glutamate- and glycine-activated currents in spinal cord
      neurones during early chick embryogenesis.
AB  - 1. The membrane currents elicited by L-glutamate and glycine applications in
      morphologically different neurone types were investigated in isolated spinal cord
      cells from the lumbar enlargement of 6 to 11-day-old chick embryos. The whole
      cell patch-clamp technique and concentration clamp methods have been used.
      Isolated spinal cord neurones of four stages were investigated: 6, 7.5, 9 and 11
      days of incubation (29th, 32nd, 35th and 37th stages of development,
      respectively). 2. The L-glutamate-activated conductance consisted of
      desensitizing and non-desensitizing components. The Hill coefficient for the
      first component was 1, and for the second was 2. The number of cells responding
      to L-glutamate application with only a desensitizing component decreased from
      53.4% on the 6th day of incubation to 6.7% on the 11th day, whereas the number of
      cells responding with bicomponent responses increased during the same period from
      13.3 to 87%. 3. From the 6th and 11th day of chick embryo development the
      characteristics of the desensitizing component of L-glutamate-activated
      conductance remained constant (half-maximal dose, (ED50 = 2.6 +/- 0.3 mM) whereas
      the ED50 for the non-desensitizing component decreased 10 times. 4. It was found
      that the density of the desensitizing L-glutamate-activated ionic current
      increased during morphological and age-dependent differentiation of spinal cord
      cells. 5. Of the investigated cells 88.7% were sensitive to glycine application.
      The smallest percentage of neurones responding to glycine application was
      observed at 7.5 days of incubation. Glycine-activated conductance did not change
      at the investigated stages (ED50, 71 +/- 2 microM; Hill coefficient, 2). 6. A
      significant decrease in the glycine-activated current density was observed on the
      9th day of incubation in multipolar neurones with three neurites, against a
      tendency to an increase of glycine-activated ionic currents during morphological
      and age-dependent differentiation of cells. 7. Of the investigated cells 78% were
      sensitive to both glycine and L-glutamate application. A negative correlation
      between glycine- and L-glutamate-activated current densities (correlation
      coefficient, -0.71) was revealed by means of statistical analysis. 8. We conclude
      that these changes in chemosensitivity of the spinal cord neurones may underlie
      the increase in locomotor activity of the chick embryo observed on the 9th day of
      incubation.

PMID- 1974925
TI  - Synaptic inhibition in the rat hippocampus in vivo following stimulation of the
      substantia nigra and ventral tegmentum.
AB  - 1. The effects of stimulating the substantia nigra (SN) or the ventral tegmental
      area (VTA) on the excitability of cells in the rat hippocampal formation have
      been investigated in vivo. 2. A train of conditioning stimuli to either of the
      midbrain nuclei produced inhibition of evoked population spikes recorded in the
      CA1 pyramidal cell layer of the hippocampus. 3. These trains of pulses had no
      effect on the evoked synaptic field potential recorded in the stratum radiatum
      although they were effective in suppressing glutamate-induced firing of cells in
      the hippocampus. These observations suggest that the inhibition is mediated
      through a postsynaptic mechanism. 4. The inhibition of the test population spike
      was observed at a latency of 50 ms after the conditioning train to either the SN
      or the VTA but did not reach a maximum until 300-500 ms and 500-750 ms post
      conditioning, respectively. The total duration of the inhibition in each case was
      about 5 s. 5. Following stimulation of the VTA, comparable levels of inhibition
      were recorded in the ventral and dorsal hippocampus. However, after stimulation
      of the SN, significantly less inhibition was observed in the ventral hippocampus.
      6. Unlike the effects on the commissural-evoked population spike in CA1,
      stimulation of SN or VTA had no effect on perforant path-induced granule cell
      excitability in the dentate gyrus. 7. These results suggest that activity in the
      substantia nigra or ventral tegmental areas could have a powerful regulatory or
      feedback role in suppressing hippocampal excitability.

PMID- 1974926
TI  - A one-year, open, prospective study of sulfasalazine in the treatment of
      rheumatoid arthritis: adverse reactions and clinical response in relation to
      laboratory variables, drug and metabolite serum levels, and acetylator status.
AB  - Response to sulfasalazine was studied for 1 year in 45 patients with rheumatoid
      arthritis. Twenty-two patients achieved a satisfactory clinical response. Adverse
      reactions developed in 15. Hemoglobin rose, and platelet count, erythrocyte
      sedimentation rate, rheumatoid factor titer, immunoglobulins, and C3 component of
      complement fell in relation to degree of response. At 1 year, 18 patients elected
      to continue the treatment. No relationship between clinical response, adverse
      reactions, or laboratory changes and drug disposition was observed.

PMID- 1974928
TI  - Autogenous and anautogenous mosquitoes: a mathematical analysis of reproductive
      strategies.
AB  - A mathematical model is presented to compare the relative advantage of an
      anautogenous mosquito population (in which females blood feed throughout life)
      with an obligate autogenous population (in which females do not feed on blood for
      the first oviposition). The advantage is measured by the intrinsic rate of
      natural increase. Autogeny was more advantageous than anautogeny when host
      searching time (ts), the ratio of the fecundity of the first autogenous to
      anautogenous oviposition (p), the fecundity in one anautogenous oviposition (n),
      or the instantaneous death rate of the adult population (D) was large, or when
      the preimaginal period (xo), the instantaneous death rate during the preimaginal
      period (D'), or survival during blood feeding (s) was low. The parameters most
      sensitive to the advantage of autogeny were ts, p, and s. The value of n was
      insensitive, and xo, D, and D' were intermediately sensitive to autogeny.
      Conditions when autogeny was advantageous were equivalent to conditions conducive
      to high autogeny rates in facultatively autogenous species, which alter the
      expression of autogeny depending upon environmental stimuli. Data on several
      facultatively autogenous species are discussed qualitatively and quantitatively
      to demonstrate the utility of our model in considering the evolution of autogeny
      and the autogeny rate.

PMID- 1974927
TI  - A prospective nationwide cross-sectional study of NSAID usage in 1331 patients
      with ankylosing spondylitis.
AB  - Drug studies in ankylosing spondylitis (AS) are usually short term, in highly
      selected patients at academic centers. We present data on 1331 UK patients with
      AS. Patients were reviewed prospectively in 1985 and 1987. Given the nationwide
      population base we avoided biases relating to local medical preferences or market
      forces. Eighty-six percent (n = 1149) were taking medication in 1985 and 78% (n =
      1040) in 1987. The most common drug in 1985 was indomethacin (Indo) with 35%,
      followed by naproxen (N; 21%), piroxicam (P; 9%), diclofenac (D; 7%) and
      ibuprofen (6%; all others less than 5%). Two years later the figures were Indo
      34%, N 19% and D 12%. At followup, survival rates (the number remaining taking
      each drug) were Indo 75%, N 63%, P 74% and D 67%. The 2 main reasons for stopping
      a drug were lack of efficacy (Indo 10%, N 25%, P 34%, D 32%) and toxicity (Indo
      39%, N 30%, P 30%, D 40%). Sixty percent of patients taking Indo reported good or
      excellent pain relief, compared with 57% on N, 47% on P and 47% on D. Good or
      excellent stiffness relief was obtained in 55% of patients on Indo, 38% on N, 44%
      on P and 40% on D. At any one time over 75% of individuals with AS are receiving
      drug treatment. The most popular nonsteroidal antiinflammatory drug for AS in
      1985 and 1987 was Indo, which scored highest in terms of efficacy, pain relief,
      stiffness relief and survival. The survival rate over 2 years ranged from 63% (N)
      to 75% (Indo).

PMID- 1974929
TI  - Resistance of permethrin to weathering in fabrics treated for protection against
      mosquitoes (Diptera: Culicidae).
AB  - Two different methods of treating cotton and nylon-cotton fabrics with permethrin
      were evaluated for protection from mosquito bites after laboratory weathering.
      Cotton fabric treated by the individual dynamic absorption method provided
      consistently better protection than cotton fabric treated by the aerosol method.
      The nylon-cotton fabric provided similar protection regardless of the treatment
      method. After weathering, the toxic effects of both types of permethrin-treated
      fabrics treated by both methods diminished much more rapidly than did the
      repellent effect. Low residual amounts of permethrin in the fabrics provided 85%
      protection from bites against Aedes aegypti (L.) and 93% protection against
      Anopheles stephensi Liston. Permethrin-treated fabrics were effective in
      providing protection from mosquito bites for long periods, even after exposure to
      weathering, and appear to be an effective means of reducing nuisance effects and
      disease transmission by mosquitoes.

PMID- 1974930
TI  - Fine structure of the egg of Trichoprosopon digitatum (Diptera: Culicidae) and
      its relationship to egg raft formation.
AB  - Eggs of Trichoprosopon digitatum (Rondani) occur in rafts; the anterior poles are
      submerged, and the posterior two-thirds float above the water surface. Each egg
      is approximately 1,060 microns long and 270 microns wide. The hydrophilic end is
      more curved dorsally than ventrally and is covered with flattened, anteriorly
      pointed, scalelike tubercles except for a small area around the micropyle. The
      hydrophobic portion is clad in a layer of closely arrayed, small, round tubercles
      among which are positioned much larger, flattened, anteriorly directed tubercles
      with deeply fissured surfaces. At three positions equidistant around the
      periphery of the egg, narrow, tongue-shaped extensions (the embrasures) from the
      anterior hydrophilic region project posteriorly into the hydrophobic region.
      Along these embrasures, progressing posteriorly, the tubercles change in form
      from flattened and bladelike to finely tapered, then, at the extension's
      posterior two-thirds, to long filaments with well-developed terminal hooks. Eggs
      in rafts are maintained in polygonal rosettes by the interlocking of these
      filaments and hooks and the surface tension of menisci between contiguous
      embrasures.

PMID- 1974931
TI  - Insights into the function of the zinc hydroxide-Thr199-Glu106 hydrogen bonding
      network in carbonic anhydrases.
AB  - The exact functional role of the zinc hydroxide (water)-Thr199-Glu106 hydrogen
      bond network in the carbonic anhydrases is unknown. However, from the results of
      molecular dynamics simulations (MD) we are able to better define its function.
      From computer graphics analysis and MD simulations on the zinc hydroxide form of
      human carbonic anhydrase II we find that this interaction forces the hydroxide
      hydrogen atom to be in a "down" position relative to the deep water-binding
      pocket. From previous work we have found that this pocket is a high-affinity
      binding site for CO2. We also note that during the timescale of our simulation
      (126 ps) the hydrogen bonds between the hydroxide hydrogen atom and Thr199 and
      the one between Thr199 and Glu106 are not fluxional. We propose that the role of
      the zinc hydroxide (water)-Thr199-Glu106 hydrogen bond network is to lock the
      hydrogen atom in the down position in order to expose the CO2 molecule bound in
      the deep water pocket to a lone pair of the hydroxide oxygen atom. This would
      allow for the rapid reaction of the CO2 molecule around the zinc ion.
      Furthermore, if the hydroxide hydrogen atom were not locked in the down position
      the binding of CO2 to the deep water pocket could be interfered with by the
      unrestrained hydroxide hydrogen atom (e.g. the N-Zn-O-H torsion could undergo
      rotational transitions that would partially block the deep water pocket). In
      summary, the roles we ascribe to this hydrogen bonding network are (1) to allow
      for facile access of CO2 to the deep water pocket and (2) to allow for maximal
      exposure of a hydroxide oxygen lone pair to the CO2 carbon atom.

PMID- 1974932
TI  - Suppression of ethanol-induced cardiac hypertrophy by beta-adrenoceptor blockade.
AB  - The effects of D,L-propranolol and its resolved epimers on cardiac size in rats
      given ethanol, or a control diet containing maltose-dextrin, every 8 h by gavage,
      for 48 h were assessed. Co-treatment with ethanol plus saline for 48 h resulted
      in increases of approximately 10% in wet and dry heart weights, and in their
      proportional measures (g/kg body wt). Cardiac protein content was increased
      similarly. Administration of D,L-propranolol (10, 20 mg/kg), or L-propranolol (5,
      10, 20 mg/kg), suppressed the increases in response to ethanol, D-Propranolol
      (10, 20 mg/kg) was ineffective in attenuating ethanol-induced increases in heart
      weights and protein content. Values of total cardiac DNA and fractional water
      content were unaffected by any of the treatments. Adrenaline and noradrenaline
      levels in urine were elevated during 48 h of intoxication in all rats given
      ethanol. The results suggest that severe, subacute intoxication with ethanol
      induces cardiac hypertrophy. Further, the data implies that the hypertrophy is
      mediated through activation of cardiac beta-adrenoceptors.

PMID- 1974933
TI  - Arrhythmias and alpha 1-adrenoceptor binding characteristics of the guinea-pig
      perfused heart during ischaemia and reperfusion.
AB  - Guinea-pig isolated hearts were perfused by the Langendorff method. Low flow
      (10%) global ischaemia for 30 min induced ventricular tachycardia (VT) and
      fibrillation (VF) in 87.5 and 37.5% respectively of the hearts. The onset times
      for VT and VF were 15.7 +/- 1.0 and 23.5 +/- 1.6 min respectively. On reperfusion
      the incidences of VT and VF were 81.3 and 75.0% and occurred after 16.0 +/- 1.5
      and 35.0 +/- 4.9 s of reperfusion. In those hearts exhibiting arrhythmias, [3H]
      prazosin binding to alpha 1-adrenoceptors of ventricular membrane fractions was
      measured and compared with normally perfused time-matched controls. There was no
      significant change in dissociation constant (KD) or density Bmax, of binding
      throughout the control perfusion period. Similarly, the KD (0.38 +/- 0.06 nM) and
      Bmax (15.5 +/- 1.4 fmol/mg protein) values obtained during ischaemia did not
      differ significantly from the corresponding control values (0.48 +/- 0.05 nM and
      15.8 +/- 1.5 fmol/mg protein). Also, at 1 min of reperfusion the KD (0.42 +/-
      0.04 nM) and Bmax (19.3 +/- 2.0 fmol/mg protein) values were not significantly
      different from the time-matched controls (0.38 +/- 0.09 nM and 20.1 +/- 2.6
      fmol/mg protein). The same result was obtained if the crude membrane fraction
      pelleted by the initial slow spin was used. Thus, although cardiac arrhythmias
      are induced by ischaemia and reperfusion of the guinea-pig isolated perfused
      heart and previous studies have shown these to be susceptible to alpha
      adrenoceptor blockade, they are not accompanied by an increase in alpha 1
      adrenoceptor affinity or density.

PMID- 1974934
TI  - Mechanisms and modulation of multidrug resistance in primary human renal cell
      carcinoma.
AB  - Human renal cell carcinomas show a high degree of intrinsic multidrug resistance.
      In experimental cell lines, the membrane bound P-170 glycoprotein and the
      glutathione redox cycle seem to contribute to this phenomenon. P-170 may be
      inactivated by calcium antagonists; the glutathione redox cycle by buthionine
      sulfoximine. We studied the resistance patterns of 35 human renal cell carcinomas
      against vinblastine, doxorubicin and carboplatinum in a tetrazolium-based
      microculture assay. Concomitantly, P-170 expression was traced
      immunohistochemically using moab C219 and the glutathione content was determined
      enzymatically. Reversal of multidrug resistance was examined by applying the R
      stereoisomer of verapamil and/or by addition of buthionine sulfoximine. A high
      degree of chemoresistance was seen in 27 tumors against vinblastine, in 30 tumors
      against doxorubicin and in 31 tumors against carboplatinum. Chemoresponse was
      found in eight, five or four cases respectively. P-170 was detected in 70% of
      highly vinblastine resistant and in 63% of highly doxorubicin resistant tumors,
      but in none of the less resistant cases. Resistance against carboplatinum and
      doxorubicin was significantly associated with elevated glutathione levels as
      compared to less resistant renal cell carcinomas. R-verapamil lead to a strong
      reversal of vinblastine resistance and to a distinct circumvention of doxorubicin
      resistance, but revealed no effect in carboplatinum resistance. Buthionine
      sulfoximine overcame carboplatinum resistance and modified doxorubicin
      resistance, but had no influence on vinblastine resistance. The combined
      application of R-verapamil and buthionine sulfoximine reversed doxorubicin
      resistance but did not act synergistically in vinblastine or carboplatinum
      resistance. Both mechanisms, P-170 and glutathione, occurred independently of
      each other and may well explain multidrug resistance of human renal cell
      carcinomas.

PMID- 1974935
TI  - Ontogeny of bladder function in the rabbit.
AB  - Although numerous experimental studies have addressed urinary bladder
      innervation, physiology and pharmacology, little information is available
      concerning the ontogeny of bladder function. The present study describes the
      developmental aspects of bladder mass, bladder capacity, pressure development and
      emptying in white New Zealand rabbits one day of age through maturity (11 to 15
      weeks of age). The following studies were performed: Cystometry, pressure
      generation, rate of pressure generation, and emptying responses to field
      stimulation, cholinergic and purinergic stimulation using the in vitro whole
      bladder model. The results of these studies can be summarized as follows: 1) body
      weight and bladder weight increased in proportion to each other, bladder capacity
      increase proportionally with development until eight weeks of age, then increased
      substantially greater than body and bladder weight between eight and 11 to 15
      weeks of age; 2) the ability to empty is similar for all ages; 3) pressure
      responsiveness to field stimulation, bethanechol, and ATP is greater at one day?
      of age, intermediate at one week of age, and similar for the other age groups; 4)
      The response to ATP (purinergic transmitter) is of an equal magnitude to the
      cholinergic response at one day, and reduces rapidly to approximately 45% of the
      cholinergic response by four weeks. Desensitization of the bladders to ATP
      reduced the response to field stimulation in the one day bladders to a
      significantly greater degree than the other age groups. These functional results
      indicate a marked alteration in cholinergic and purinergic response between the
      one day and the four week old rabbit bladders, with the response of the one week
      old bladders in between. The responses of the four, eight, and 11 to 15 week
      bladders was similar for equal volumes even though the bladder mass increased
      over threefold. This indicates that the ability of the bladder to generate
      pressure (during development) is not directly related to bladder mass.

PMID- 1974936
TI  - Dermacentor albipictus (Acari, Ixodidae) on captive reindeer and free-ranging
      woodland caribou.
AB  - Infestations of winter ticks (Dermacentor albipictus) on two captive reindeer
      (Rangifer tarandus tarandus) are reported and may be associated with increased
      grooming and alopecia. Over 400,000 ticks were recovered from one reindeer. Few
      ticks (less than 25 ticks/animal) were found on three free-ranging woodland
      caribou (Rangifer tarandus caribou).

PMID- 1974937
TI  - Effect of combined dopamine and bunazosin on the ischemic heart after occlusion
      of the coronary artery.
AB  - In order to investigate whether dopamine combined with bunazosin improves cardiac
      function, the global and regional cardiac function and regional blood flow of 7
      anesthetized dogs were analyzed before and after occlusion of the left anterior
      descending coronary artery (LAD), then after 10 micrograms/kg/min dopamine
      infusion following the LAD occlusion, and again after a bolus infusion of
      bunazosin 250 micrograms/kg. Dopamine with bunazosin reduced left atrial pressure
      from 4.9 +/- 0.9 to 3.1 +/- 0.5 mmHg (p less than 0.05) and improved cardiac
      output from 1.22 +/- 0.15 to 1.50 +/- 0.14 L/min (p less than 0.05), maximum
      positive left ventricular dp/dt from 1721 +/- 202 to 3600 +/- 663 mmHg/sec (p
      less than 0.05) and the time constant from 45.2 +/- 5.0 to 27.5 +/- 4.6 msec (p
      less than 0.01). Bunazosin added to the dopamine reduced the elevated left
      ventricular peak systolic pressure caused by dopamine from 130 +/- 7 to 113 +/- 8
      mmHg (p less than 0.01). With regard to the regional wall motion, the impaired
      LAD-delta L (the segment systolic shortening) and LAD-Elmax (the slope of peak
      systolic pressure--endsystolic length relation) following the LAD occlusion
      improved from 0.5 +/- 2.5 per cent to 5.9 +/- 2.6 per cent (p less than 0.01) and
      from 50 +/- 9 to 82 +/- 14 mmHg/mm (p less than 0.01) after the infusion of
      dopamine with bunazosin. Dopamine greatly increased the Rate Pressure Product
      (RPP) from 12610 +/- 1120 after LAD occlusion to 16950 +/- 1420, whereas dopamine
      in combination with bunazosin did not increase the RPP due to a drop of LV-PSP
      with little change in regional myocardial blood flow. It was concluded that
      combining dopamine with bunazosin was useful for improving both the global and
      regional cardiac functions of the ischemic heart.

PMID- 1974939
TI  - [Updated view of the treatment of unilateral cryptorchism].

PMID- 1974938
TI  - Adhesion molecules in the prognosis of diffuse large-cell lymphoma: expression of
      a lymphocyte homing receptor (CD44), LFA-1 (CD11a/18), and ICAM-1 (CD54).
AB  - Adhesive interactions between lymphocyte cell-surface receptors and components of
      the vascular endothelium and the extracellular matrix play an important role in
      the control of lymphocyte migration and homing. To investigate whether lymphocyte
      adhesion molecules involved in the migration of normal lymphocytes, i.e., CD44
      homing receptor, LFA-1 (CD11a/18), and ICAM-1 (CD54), also play a role in the
      spread and hence in the disease course of non-Hodgkin's lymphomas (NHL),
      expression of these molecules was examined in 78 cases of diffuse large-cell
      lymphoma. Other potential risk factors considered in this study were sex, age,
      primary tumor localization, lineage (T cell vs. B cell), and histopathological
      subtype. 27 of 53 (51%) patients with a lymphoma having a high CD44 antigen
      expression showed tumor spread beyond stage II at diagnosis while this was the
      case in only three of 25 (12%) patients with lymphomas that were CD44
      low/negative (chi-square 25.4, p less than 0.001). Similarly, poor response to
      treatment, i.e., absence of remission or relapse, and or death from lymphoma, was
      more common among patients with lymphomas expressing high levels of CD44;
      actuarial survival among patients with CD44 high and low lymphomas was 47% and
      91%, respectively (Mantel-Cox 6.1, p = 0.02). Neither LFA-1 nor ICAM-1 expression
      showed a significant correlation to lymphoma dissemination or disease course. Of
      the other factors considered, T cell phenotype was associated with an unfavorable
      prognosis while nodal localization was a risk factor for dissemination. Taken
      together, our findings suggest that CD44 antigen expression plays an important
      role in the dissemination of NHL and via this mechanism exerts an unfavorable
      prognostic influence.

PMID- 1974940
TI  - Ultrasound screening and perinatal mortality: controlled trial of systematic one
      stage screening in pregnancy. The Helsinki Ultrasound Trial.
AB  - During a 19-month period, 95% of all pregnant women in the greater Helsinki area,
      Finland, entered a study to compare one-stage ultrasonography screening with
      selective screening according to antenatal hospital use, obstetric procedures,
      and fetal outcomes. Of 9310 women who entered the trial, 4691 were randomly
      allocated to ultrasound screening between the 16th and 20th gestational weeks and
      4619 to follow-up only. Screened and control groups otherwise had the same
      antenatal care, which included ultrasonography according to usual practice.
      Screened women made fewer visits to the antenatal outpatient clinic than did
      women in the control group (2.3 vs 2.6). There were no differences in the number
      of labour inductions or mean birthweights in the two groups. Perinatal mortality
      was significantly lower in the screened than in the control group (4.6/1000 vs
      9.0/1000); this 49.2% reduction was mainly due to improved early detection of
      major malformations which led to induced abortion. All twin pregnancies were
      detected before the 21st gestational week in the screening group compared with
      76.3% in the control group; perinatal mortality in the small series of twins was
      27.8/1000 vs 65.8/1000, respectively.

PMID- 1974941
TI  - Enhancement of recovery from psychiatric illness by methylfolate.
AB  - 41 (33%) of 123 patients with acute psychiatric disorders (DSM III diagnosis of
      major depression or schizophrenia) had borderline or definite folate deficiency
      (red-cell folate below 200 micrograms/l) and took part in a double-blind, placebo
      controlled trial of methylfolate, 15 mg daily, for 6 months in addition to
      standard psychotropic treatment. Among both depressed and schizophrenic patients
      methylfolate significantly improved clinical and social recovery. The differences
      in outcome scores between methylfolate and placebo groups became greater with
      time. These findings add to the evidence implicating disturbances of methylation
      in the nervous system in the biology of some forms of mental illness.

PMID- 1974942
TI  - Do changes in pattern of breast usage alter the baby's nutrient intake?
AB  - Twelve mother/baby pairs took part in a study of the difference in effect of two
      patterns of breast feeding--either feeding at one breast or at two breasts during
      a feed. Baseline measures were taken at 4 weeks, and the test patterns of feeding
      were followed for a week each, in random order. The two patterns of feeding led
      to differences in milk volume intake and mean feed fat concentration, but not in
      the baby's net fat intake per 24 h. The results indicate that the breast-fed baby
      can regulate his fat intake quickly and thus mothers should be encouraged to
      practice "baby-led" feeding.

PMID- 1974943
TI  - Recurrent lesions in human Leishmania braziliensis infection--reactivation or
      reinfection?
AB  - Strains of Leishmania braziliensis subspecies isolated from initial and recurrent
      lesions in 24 patients from the Pacific coast of Colombia were examined for
      distinguishing polymorphisms by enzyme electrophoresis, restriction endonuclease
      analysis of kDNA, and molecular karyotyping of nuclear DNA. Recurrent strains
      from 12 patients (50%) were identical to the initially infecting strain by all
      methods of characterisation. Phenotypic and genotypic identity, together with
      clinical data, support endogenous reactivation as the mechanisms of recurrent
      disease in these 12 patients. 5 of the 24 (22%) recurrent strains differed from
      the initial strain by all methods. The remaining 7 strain pairs, not separated by
      enzyme polymorphisms, showed differing schizodeme and/or karyotype profiles.
      Patients whose recurrent lesions were caused by strains different from those
      causing the initial lesions had a significantly longer disease-free interval than
      patients whose lesions were caused by identical strains. Recurrent lesions
      occurred further from initial lesions in the former than in the latter group.
      Exogenous reinfection is the most plausible explanation for recurrences due to
      disparate organisms. These findings have important implications for both
      treatment evaluation and vaccination strategies for American tegumentary
      leishmaniasis.

PMID- 1974945
TI  - Hantavirus disease.

PMID- 1974944
TI  - Pancreatic islet transplantation after upper abdominal exenteration and liver
      replacement.
AB  - Nine patients who became diabetic after upper-abdominal exenteration and liver
      transplantation were given pancreatic islet-cell grafts obtained from the liver
      donor (eight cases), a third-party donor (one), or both (four). Two patients were
      diabetic when they died of infections after 48 and 109 days, as was a third
      patient who died of tumour recurrence after 178 days. The other 6 are alive 101
      186 days postoperatively, and five are insulin-free or on insulin only during
      night-time parenteral alimentation. C-peptide increased 1.7 to 3.3 fold in
      response to intravenous glucose in these five patients who have had glycosylated
      haemoglobin in the high normal range. However, the kinetics of the C-peptide
      responses to intravenous glucose in all eight patients tested revealed an absent
      first-phase release and a delayed peak response consistent with transplantation
      and/or engraftment of a suboptimal islet cell mass. The longest survivor, who
      requires neither parenteral alimentation nor insulin, is the first unequivocal
      example of successful clinical islet-cell transplantation.

PMID- 1974946
TI  - Real insight.

PMID- 1974947
TI  - Cuff-link.

PMID- 1974948
TI  - Endobronchial treatment for tracheobronchial tumours.

PMID- 1974949
TI  - Endoscopic transanal resection.

PMID- 1974950
TI  - Precocious familial gout.

PMID- 1974951
TI  - Relation between severity and extent of precancerous lesions in the postoperative
      stomach.
AB  - The relation between the severity and extent of precancerous lesions in a
      precancerous condition of the stomach was assessed, to find a means of reducing
      the endoscopic workload required for the detection of such lesions. 87 subjects
      who had had gastric surgery for peptic ulcer more than 20 years ago underwent
      gastric endoscopy and biopsy. Severity of dysplasia correlated with its extent.
      Severity of intestinal metaplasia correlated with its extent and with severity of
      dysplasia. Type of operation, but not sex or type of ulcer, was the factor most
      strongly associated with dysplasia. Previous Billroth II operations were more
      strongly associated with occurrence of dysplasia (85%) than were other
      operations. In patients with previous Billroth II operations, moderate and severe
      dysplasia were commoner around the stoma (37%) than in the body (10%). These
      findings indicate that there is a relation between the severity and extent of
      precancerous lesions, which suggests that patients with dysplasia have widespread
      gastric mucosal instability. They also indicate that, if endoscopic screening is
      limited to Bilroth II subjects and if biopsies are limited to the stoma,
      endoscopic workload can be reduced by 85%, with only a small reduction (15%) in
      detection of moderate and severe dysplasia.

PMID- 1974952
TI  - Myeloid neoplasia in children treated for solid tumours.
AB  - Therapy-related myeloid neoplasia developed 14 to 189 months after diagnosis of
      the primary malignancy in 12 out of 3365 children treated for malignant solid
      tumours; 6 of the 12 were in their first complete remission. The 10-year
      cumulative incidence of myeloid neoplasia was 1.3% (95% Cl 0.5-3.6) for the 447
      patients with Hodgkin's disease, 1.3% (0.4-4.3) for the 420 with non-Hodgkin
      lymphoma, and 1.2% (0.3-5.2) for the 440 with neuroblastoma. This complication
      appeared in 1 of 180 children with brain tumours and in none of the 1878 with
      other malignancies. Risk of therapy-related myeloid neoplasia in patients with
      Hodgkin's disease was associated with recurrence of the primary malignancy, a
      combination of radiotherapy and chemotherapy with alkylating agents, and age
      greater than or equal to 12 years at diagnosis of Hodgkin's disease. Of the 8
      patients who underwent chromosomal analysis of neoplastic myeloid cells, 2 showed
      complete loss of chromosome 7 and 4 showed t(9;11) or t(8;21) with or without
      del(16)(q22). The 2 patients who had received an epipodophyllotoxin had an 11q23
      abnormality. The risk of therapy-related myeloid neoplasia is low in children
      with malignant solid tumours.

PMID- 1974953
TI  - Comparison of audible sound transmission with ultrasound in screening for
      congenital dislocation of the hip.
AB  - In a comparative study ultrasound and the sound transmission test were used to
      seek congenital dislocation of the hip in 102 babies referred to a paediatric
      orthopaedic clinic. The sound transmission test correctly identified all those
      hips considered normal or dislocated on ultrasound. 17 babies underwent repeated
      ultrasound examination for hips considered abnormal but not dislocated. 12
      improved and 5 required treatment. With a cut-off decibel difference between the
      hips of 5.8 dB the sound transmission test correctly identified the dislocated
      hips but did not detect some of the hips that needed treatment. A cut-off of 5.6
      dB reduced the likelihood of a false-negative result while maintaining the
      sensitivity of the test.

PMID- 1974954
TI  - New antiepileptic agents: strategies for drug development.

PMID- 1974955
TI  - New and potential anticonvulsants.

PMID- 1974956
TI  - Management of epilepsy during pregnancy and lactation.

PMID- 1974957
TI  - Doctors with HIV.

PMID- 1974958
TI  - Occult axillary lymph-node micrometastases in breast cancer.

PMID- 1974959
TI  - Detection of early ovarian cancer.

PMID- 1974960
TI  - Fenoterol and fatal asthma.

PMID- 1974961
TI  - Controlled release prostaglandin E2 pessaries.

PMID- 1974962
TI  - In vivo assessment of N-acetylaspartate in brain in spongy degeneration
      (Canavan's disease) by proton spectroscopy.

PMID- 1974963
TI  - Antibodies to cerebellar soluble lectin in multiple sclerosis.

PMID- 1974964
TI  - Cyclosporin treatment for severe active ulcerative colitis.

PMID- 1974965
TI  - GISSI-2: 10% reduction in mortality with heparin in acute myocardial infarction?

PMID- 1974966
TI  - Treatment of testicular cancer in Poland.

PMID- 1974967
TI  - Outbreaks of drug-resistant tuberculosis at AIDS centre.

PMID- 1974968
TI  - Zidovudine with probenecid.

PMID- 1974969
TI  - Re-analysis of clinical trial of homoeopathic treatment in fibrositis.

PMID- 1974970
TI  - Blackfoot disease.

PMID- 1974971
TI  - Zinc supplementation during diarrhoea, a fortification against malnutrition?

PMID- 1974972
TI  - How much of which antipsychotic?

PMID- 1974973
TI  - Parvovirus B19 infection in the fetus.

PMID- 1974974
TI  - Judgment of alleged malpractice.

PMID- 1974975
TI  - Research in surgery: comparison of British and American practice.

PMID- 1974976
TI  - Asbestos and the Romans.

PMID- 1974977
TI  - Hysterectomy or what?

PMID- 1974978
TI  - Reconstitution of interleukin-2.

PMID- 1974979
TI  - Perforation of colon in distal intestinal syndrome of cystic fibrosis.

PMID- 1974980
TI  - Phrenic nerve stimulation in quadriplegia.

PMID- 1974981
TI  - Alanine aminotransferase screening and hepatitis C virus antibody.

PMID- 1974982
TI  - Hepatitis C virus RNA in symptomless donors implicated in post-transfusion non-A,
      non-B hepatitis.

PMID- 1974983
TI  - Airborne house dust mite antigen after vacuum cleaning.

PMID- 1974984
TI  - Calcitonin nasal spray for painful diabetic neuropathy.

PMID- 1974985
TI  - Dehydroepiandrosterone sulphate in Alzheimer's disease.

PMID- 1974986
TI  - Regional cerebral blood flow in Alzheimer's disease.

PMID- 1974987
TI  - Detection of Pneumocystis carinii with DNA amplification.
AB  - Oligonucleotide primers and probes were used in the polymerase chain reaction to
      amplify Pneumocystis carinii specific DNA sequences from alveolar lavage samples
      from 47 diagnostic bronchoscopies. No P carinii DNA was found in lavage from 10
      immunocompetent patients; only low levels were found in 3 of 13 samples from
      immunosuppressed individuals without P carinii pneumonia (PCP), and the highest
      levels, readily demonstrated by simple ethidium bromide staining, were found in
      all of 16 samples from immunosuppressed patients with PCP confirmed by means of
      standard silver staining and in 4 from patients with clinical PCP but negative
      silver staining. DNA amplification provides a highly sensitive and specific
      technique for the identification of P carinii that should be valuable in
      epidemiological studies on this parasitic infection and in diagnosis.

PMID- 1974988
TI  - Specificity of hypoglycaemia for cerebral malaria in children.
AB  - Glycaemic status on hospital admission was compared in 97 children with severe
      falciparum malaria (36 with cerebral malaria) and 89 children with other serious
      illnesses (32 in coma; 57 with acute pneumonia, not in coma). The frequency of
      hypoglycaemia (blood glucose below 2.2 mmol/l) did not differ significantly
      between malarial and control patients (5.2% vs 11.2%) nor between the comatose
      (11.1% vs 18.8%) and conscious (1.6% vs 7.0%) malarial and control subgroups.
      Compared with normoglycaemic patients, hypoglycaemic patients had appropriately
      low serum insulin (3.0 vs 8.2 mU/l) and C-peptide (0.13 vs 0.42 mmol/l) and high
      plasma non-esterified fatty acids (1.42 vs 0.83 mmol/l). Hypoglycaemia, the level
      of consciousness, and death were all significantly associated with the time since
      the last meal. Hypoglycaemia is not a specific complication of malaria but is
      found in severely ill fasted children, resulting from glycogen depletion and
      perhaps impaired hepatic gluconeogenesis. It should be sought in all severely
      sick children. A single bolus dose of glucose may not be enough to correct it.

PMID- 1974989
TI  - Regression of hypertensive left ventricular hypertrophy and left ventricular
      diastolic function.
AB  - The effect of antihypertensive therapy on regression of left ventricular
      hypertrophy and left ventricular diastolic function was investigated in 25
      hypertensive patients for up to 18 months after initiation of treatment. Left
      ventricular mass index was calculated by two-dimensional echocardiography and
      left ventricular diastolic function assessed by transmitral pulsed doppler
      ultrasound. Significant reduction in left ventricular mass index was observed
      after 9 months of treatment. Only 13 patients had a reduction in mass greater
      than the intraobserver variability of the technique. There was no change in
      doppler indices of left ventricular diastolic function. In 7 patients who were
      studied for a further 9 months after regression had occurred there was still no
      appreciable difference in left ventricular diastolic function. These findings
      indicate that there is no direct relation between left ventricular mass and
      abnormal left ventricular diastolic function.

PMID- 1974990
TI  - Aluminium deposition in bone after contamination of drinking water supply.
AB  - Two healthy individuals who drank water accidentally contaminated at source with
      aluminium sulphate solution were investigated 6-7 months later. Bone biopsy
      specimens showed discrete lines of positive staining for aluminium, the
      distribution being compatible with acute exposure some months previously. These
      findings show that under certain conditions normal individuals can absorb
      aluminium via the gut, and that such aluminium can be deposited in bone.

PMID- 1974991
TI  - Preliminary report: furunculosis and hypoferraemia.
AB  - 16 patients with recurrent staphylococcal furunculosis but without anaemia had
      significantly lower serum iron concentrations than normal laboratory reference
      values, 8 controls with single furuncles, or 10 controls with acne conglobata.
      There were no significant differences in serum glucose or iron binding capacity
      between the groups studied. Furunculosis resolved after 3-4 weeks' treatment with
      iron supplements in all but 1 patient. The relation between iron and
      susceptibility to infection is unclear, but merits further investigation.

PMID- 1974992
TI  - Thin-membrane nephropathy--how thin is thin?

PMID- 1974993
TI  - Consensus on IVIG.

PMID- 1974994
TI  - Measuring sunscreen protection against UVA.

PMID- 1974995
TI  - Bismuth and dyspepsia.

PMID- 1974996
TI  - Coping with three, four, or more.

PMID- 1974997
TI  - International trends in cancer mortality in France, West Germany, Italy, Japan,
      England and Wales, and the USA.
AB  - Age-specific worldwide trends in cancer mortality were reviewed, with emphasis on
      cancer sites where increases have been reported in the USA. Cancer rates vary by
      factors as high as 30 between all countries, and 5-fold within and between
      industrialised countries. In Italy, Japan, Federal Republic of Germany, England
      and Wales, and the USA, patterns of cancer mortality have shifted uniformly over
      the past two decades. Stomach cancer continues to decline, while brain and other
      central-nervous-system cancer, breast cancer, multiple myeloma, kidney cancer,
      non-Hodgkin lymphoma, and melanoma have increased in persons aged 55 and older.
      Cancer of the lung is starting to decline for men under age 85 and women under
      age 60 in England and Wales and men under age 45 in the USA, but is still rising
      for men and women in other countries. All forms of cancer are increasing in
      persons over age 54 except lung and stomach (which together comprise between 20%
      and 43% of all cancer in males in these countries). Studies of the quality of
      ascertainment and enumeration indicate that these increases are not attributable
      solely to diagnostic artifacts or to increased access to health care, although
      both these factors may be involved. These recorded increases in cancer should be
      assessed in greater detail to provide better projections of health care needs and
      to identify causal factors that may be controlled. The changes in cancer other
      than lung are so great and rapid that their causes demand intensive
      investigation.

PMID- 1974998
TI  - Comparison of CAGE questionnaire and computer-assisted laboratory profiles in
      screening for covert alcoholism.
AB  - To identify the most effective method of screening for covert alcoholism Ewing's
      CAGE questionnaire was compared with several computer-assisted laboratory data
      profiles in a prospectively gathered, random sample of 915 adults admitted to a
      general hospital. Whether a subject was alcohol dependent (n = 244) or not (n =
      671), as defined by DSM-III-R, was determined on the basis of a structured
      interview. The CAGE questionnaire was highly sensitive (76%) and specific (94%)
      for recognition of alcohol dependence (positive predictive power 87%). None of
      the discriminant laboratory functions gave recognition rates greater than chance
      alone. Until the sensitivities, specificities, and positive predictive powers of
      computer-assisted methods improve, brief interview alone remains the best
      screening method for general hospital populations.

PMID- 1974999
TI  - Childhood epileptic syndromes.

PMID- 1975000
TI  - Treatment of epilepsy and febrile convulsions in children.

PMID- 1975001
TI  - Inequalities in health: ten years and little further on.

PMID- 1975002
TI  - Diet, cystic fibrosis, and diabetes: making friends with the perfect enemy.

PMID- 1975003
TI  - Skin cancer and the ozone shield.

PMID- 1975004
TI  - Bone density screening for osteoporosis.

PMID- 1975005
TI  - Hepatitis C virus transmitted by human bite.

PMID- 1975006
TI  - Long-term use of copper intrauterine devices.

PMID- 1975007
TI  - Vigabatrin and behaviour disturbances.

PMID- 1975008
TI  - Lack of association between anticardiolipin antibodies and heart valve disease in
      Chinese patients with systemic lupus erythematosus.

PMID- 1975009
TI  - Anticardiolipin antibodies and binding of anionic phospholipids and serum
      protein.

PMID- 1975010
TI  - beta-blockers and variceal haemorrhage.

PMID- 1975011
TI  - HLA-DR3 and immunoresponsiveness.

PMID- 1975012
TI  - The trouble with T cells.

PMID- 1975013
TI  - Mixed gastric infection by Gastrospirillum hominis and Helicobacter pylori.

PMID- 1975014
TI  - Partner notification for HIV in Sweden.

PMID- 1975015
TI  - "Treating through" hypersensitivity to cotrimoxazole in children with HIV
      infection.

PMID- 1975016
TI  - Deep venous thrombosis and antibodies to cyproterone acetate.

PMID- 1975017
TI  - Rapid progression to AIDS in dual HIV-1/HTLV-I infection.

PMID- 1975018
TI  - Risk assessment.

PMID- 1975019
TI  - Obstetrics and technology.

PMID- 1975020
TI  - Doctors and nurses.

PMID- 1975021
TI  - Down's syndrome and fertility in older women.

PMID- 1975022
TI  - Abnormal distribution of CF delta F508 allele in azoospermic men with congenital
      aplasia of epididymis and vas deferens.

PMID- 1975023
TI  - Oxygen concentrator malfunction.

PMID- 1975024
TI  - Anti-glomerular basement membrane disease after renal obstruction.

PMID- 1975025
TI  - Response of long-running Alternaria alternata infection to fluconazole.

PMID- 1975026
TI  - Antibiotic resistance of Listeria monocytogenes.

PMID- 1975027
TI  - Detection of anti-BCG secreting cells in cerebrospinal fluid.

PMID- 1975029
TI  - Immunocytochemical confirmation of prion protein.

PMID- 1975028
TI  - Mutation in codon 200 of scrapie amyloid protein gene in two clusters of
      Creutzfeldt-Jakob disease in Slovakia.

PMID- 1975030
TI  - Dementia with beta-amyloid deposition: involvement of alpha B-crystallin supports
      two main diseases.

PMID- 1975031
TI  - Latex as aeroallergen.

PMID- 1975032
TI  - How maximal is "maximum"?

PMID- 1975033
TI  - Xamoterol in severe heart failure.

PMID- 1975034
TI  - Apomorphine test in parkinsonian syndromes.

PMID- 1975035
TI  - Bacterial ileocaecitis and appendicitis.

PMID- 1975036
TI  - Liver transplantation across ABO blood group barriers.
AB  - In a study of 234 liver transplants the 2-year graft survival for ABO-compatible
      elective (80%) or emergency (76%) liver transplants was significantly higher than
      that for ABO-incompatible emergency liver transplants (30%). The low survival of
      ABO-incompatible liver allografts was therefore not related to the emergency
      conditions. Among 17 patients who received ABO-incompatible liver allografts,
      primary humoral rejection, with haemorrhagic infiltration of portal tracts and
      deposition of IgM and fibrinogen on sinusoidal and endothelial cells, developed
      in 6. Other disadvantages of ABO-incompatible liver allografts were significantly
      higher frequencies of severe rejection crises, arterial thrombosis, and
      cholangitis. However, the 1-year survival rate of the patients who received ABO
      incompatible grafts was 66%, so the use of ABO-incompatible liver grafts is
      justifiable in emergencies, when no other donor is available; such transplants
      may help to save the patient, even at the cost of retransplantation in half of
      the cases.

PMID- 1975037
TI  - Does glutamine contribute to immunosuppression after major burns?
AB  - The effects of glutamine concentration on the rates of lymphocyte proliferation
      after mitogenic stimulation and of phagocytosis by macrophages were investigated
      in vitro. A decrease in the glutamine concentration in culture medium from 0.6 to
      0.05 mmol/l greatly decreased the rate of proliferation of human lymphocytes and
      of phagocytosis by mouse macrophages. In patients with major burn injury plasma
      glutamine concentration was 58% lower than that in normal controls and it
      remained low for at least 21 days after the injury. The findings indicate that
      the decrease in plasma glutamine concentration may contribute to the injury
      induced impairment of immune function occurring after major burn injury.

PMID- 1975038
TI  - Long-term toxicity/activity profile of 2',3'-dideoxyinosine in AIDS or AIDS
      related complex.
AB  - To evaluate the long-term toxicity and activity profile of 2',3'-dideoxyinosine
      (ddI), a potent inhibitor of human immunodeficiency virus (HIV) replication, in
      vitro. 58 patients with AIDS or AIDS-related complex were studied with additional
      reference to the effect of previous treatment with zidovudine, and the effect of
      ddI on HIV-induced cognitive dysfunction. Doses above 9.6 mg/kg per day of ddI
      were frequently associated with toxicity (peripheral neuropathy, pancreatitis, or
      hepatitis). Doses of 9.6 mg/kg per day or below were well tolerated for up to 21
      months. A subset of patients receiving 3.2-9.6 mg/kg per day of ddI had long-term
      immunological improvement and reduction of serum HIV p24 antigen. Immunological
      changes were especially seen in patients who had little previous zidovudine
      therapy. 5 patients with HIV-induced cognitive impairment improved with ddI.
      Thus, ddI may have anti-HIV activity at doses which are tolerated for long-term
      therapy, although pancreatitis could be a life-threatening complication.

PMID- 1975039
TI  - Genotyping of poor metabolisers of debrisoquine by allele-specific PCR
      amplification.
AB  - A method for genotyping poor metabolisers of debrisoquine is based on specific
      polymerase chain reaction (PCR) amplification of parts of mutant genes for
      hepatic cytochrome P450IID6. Analysis by restriction fragment length polymorphism
      allowed identification of only 25% of poor metabolisers, but when it was combined
      with allele-specific PCR over 95% of poor metabolisers could be identified. The
      PCR method also allowed the identification of heterozygous carriers of mutant
      alleles.

PMID- 1975040
TI  - Preliminary report: renal thromboxane A2 synthesis in children with frequent
      relapsing nephrotic syndrome.
AB  - An evaluation was made of the possible relation between renal thromboxane (Tx)A2
      synthesis (measured as urinary excretion of TxB2) and the loss of glomerular
      permeability to proteins, in 5 children with seven episodes of minimal change
      nephrotic syndrome. Urinary TxB2 excretion was significantly higher in children
      with minimal change nephrotic syndrome than in 14 healthy controls, and reached
      its maximum at the time of peak proteinuria. During remission of nephrotic
      syndrome urinary excretion of TxB2 was still significantly higher than in healthy
      controls. A significant positive correlation between urinary excretion of TxB2
      and proteinuria was observed in 3 patients. The results suggest that renal TxA2
      could be regarded as one of the possible mediators of the altered glomerular
      permeability to proteins in minimal change nephrotic syndrome.

PMID- 1975041
TI  - Postherpetic neuralgia.

PMID- 1975042
TI  - Tolerance and the fetal graft.

PMID- 1975043
TI  - Children who walk late.

PMID- 1975044
TI  - Taking risks in general practice.

PMID- 1975045
TI  - Treatment adherence and risk of death after a myocardial infarction.
AB  - The relation of treatment adherence to mortality after a myocardial infarction
      was investigated among 2175 participants in the Beta Blocker Heart Attack Trial,
      which had data for measures of treatment adherence, clinical severity, and the
      psychological and social features that may influence post-infarction mortality.
      Overall, patients who did not adhere well to treatment regimen (ie, who took less
      than or equal to 75% of prescribed medication) were 2.6 times more likely than
      good adherers to die within a year of follow-up (95% confidence interval, 1.2,
      5.6). Poor adherers had an increased risk of death whether they were on
      propranolol (OR = 3.1) or placebo (OR = 2.5). Furthermore, this increased risk of
      death for poor adherers was not accounted for by measures of the severity of
      myocardial infarction, sociodemographic features (eg, race, marital status,
      education), smoking, or psychological characteristics (high life-stress or social
      isolation).

PMID- 1975046
TI  - Life-threatening bacteraemia in HIV-1 seropositive adults admitted to hospital in
      Nairobi, Kenya.
AB  - During 6 months, 506 consecutive adult emergency admissions to hospital in
      Nairobi were enrolled in a study of bacteraemia and HIV infection. 19% were HIV-1
      antibody positive. Significantly more HIV-seropositive than seronegative patients
      had bacteraemia (26% vs 6%). The predominant organisms isolated from the
      seropositive patients were Salmonella typhimurium and Streptococcus pneumoniae.
      Mortality was higher in the seropositive than in the seronegative bacteraemic
      patients. The findings suggest that non-opportunistic bacteria are important
      causes of morbidity and mortality in HIV-infected individuals in Africa.

PMID- 1975048
TI  - Status epilepticus in adults.

PMID- 1975047
TI  - Inconsistencies in clinical decisions in obstetrics.
AB  - Analysis of the increasing incidence of caesarean section in an English teaching
      hospital over a 15-year period revealed that emergency caesarean section for the
      diagnosis of fetal distress in labour made a major contribution to this
      increasing trend. A retrospective audit of a sample of these operations by the
      consultants of the hospital indicated that 30% of the operations were
      unnecessary. There were two other disturbing findings in our audit. First, there
      was significant disagreement between auditors in the decision whether to do a
      caesarean section or not. Second, and perhaps more importantly, when faced with
      identical information at a different time, the auditors were inconsistent in 25%
      of cases. The disturbing clinical situation highlighted by this study may have
      implications for medical jurisprudence.

PMID- 1975049
TI  - Surgical treatment of epilepsy.

PMID- 1975050
TI  - Coroners and allegations of lack of care, UK and Hong Kong.

PMID- 1975051
TI  - Controlled-release prostaglandin E2 pessary and cervical ripening.

PMID- 1975052
TI  - Screening for uterine neoplasms.

PMID- 1975053
TI  - Impaired driving fitness after electrical or magnetic cortical stimulation.

PMID- 1975054
TI  - Induction chemotherapy in Jehovah's Witnesses with leukaemia.

PMID- 1975055
TI  - Treatment of breast cancer in elderly patients.

PMID- 1975056
TI  - Delusional bovine spongiform encephalopathy.

PMID- 1975057
TI  - Fluconazole-induced jaundice.

PMID- 1975058
TI  - Cyclophosphamide for chronic relapsing thrombotic thrombocytopenic purpura.

PMID- 1975059
TI  - Transcatheter closure of atrial septal defects.

PMID- 1975060
TI  - Arrhythmia due to hypervagotonia in a fit pharmacology volunteer.

PMID- 1975061
TI  - Operator radiation exposure and cardiac catheterisation route.

PMID- 1975062
TI  - Right-to-left shunt and neurological decompression sickness in divers.

PMID- 1975063
TI  - Antibiotics for marine vibrios.

PMID- 1975064
TI  - Pain relief in neonatal intensive care.

PMID- 1975065
TI  - Growth and nutrition in children with cerebral palsy.

PMID- 1975066
TI  - Rectal gluten challenge and diagnosis of coeliac disease.

PMID- 1975067
TI  - Antibodies to thymic hormone and HLA-DQ in type I diabetes.

PMID- 1975068
TI  - Aetiology of eosinophilic enteritis.

PMID- 1975070
TI  - Judicial amputation and human rights.

PMID- 1975071
TI  - Chiropractors and low back pain.

PMID- 1975069
TI  - Antibodies to Helicobacter pylori in HIV infection.

PMID- 1975072
TI  - Overexpression of P-glycoprotein in adult T-cell leukaemia.

PMID- 1975073
TI  - Endogenous steroids and pathogenesis of hepatic encephalopathy.

PMID- 1975074
TI  - Multiple cutaneous haemangiomas in patient with disseminated renal cell carcinoma
      and polycythaemia.

PMID- 1975075
TI  - Kaposi's sarcoma and HTLV-I infection.

PMID- 1975076
TI  - Tyrosine hydroxylase polymorphisms and manic-depressive illness.

PMID- 1975077
TI  - HTLV-II infection in Italian drug abusers.

PMID- 1975078
TI  - Benzodiazepines and fantasy.

PMID- 1975079
TI  - Legionella and fountains.

PMID- 1975080
TI  - H1 antihistamines interact with central sigma receptors.
AB  - Several antihistamines were evaluated for their ability to interact with sigma,
      muscarinic and histaminic H1 binding sites in rat brain preparations. All of the
      antihistamines were able to interact with the sigma site, as well as the other
      two sites. In addition, tripelennamine was found to elicit sigma-like behaviors
      when administered to rats. This affinity for the sigma site suggests that the
      compounds may elicit some of their undesirable CNS side effects via this
      interaction.

PMID- 1975081
TI  - The effects of 5-HT1B characterizing agents in the mouse elevated plus-maze.
AB  - Although the serotonergic system has been implicated in the modulation of anxiety
      states, the specific receptor subtypes that mediate these states require
      clarification. The effects of drugs that act preferentially at 5-HT1B receptors
      were evaluated on the behavior elicited in the elevated plus-maze, an animal
      model of anxiety. Variations in the intensity of light affected mouse behavior in
      the plus-maze; lower light intensity increased the entries to and time spent on
      the open arm in a manner similar to that seen with stress-attenuating
      circumstances. Opposite effects were observed in high light-intensity, similar to
      effects seen under elevated stress conditions. Chlordiazepoxide produced
      increased entries and time spent on the open arm, whereas pentylenetetrazol (PTZ)
      produced opposite effects. The preferential 5-HT1B agents TFMPP and mCPP
      exhibited a profile similar to PTZ. The effects of TFMPP in the plus-maze were
      reversed by chlordiazepoxide, but not by the benzodiazepine receptor antagonist
      flumazenil, which suggests that this effect is not directly mediated by
      benzodiazepine receptors. The decreased entries and time spent on the open arm of
      the maze following TFMPP or mCPP administration was possibly mediated by an
      antagonistic action at 5-HT1B receptors, since this effect was reversed by the
      selective 5-HT1B agonist CGS 12066B. The present study further demonstrates the
      utility of mouse behavior in the elevated plus-maze as a model for identifying
      anxio-modulatory substances.

PMID- 1975082
TI  - Kappa opioid receptors stimulate phosphoinositide turnover in rat brain.
AB  - The effects of various subtype-selective opioid agonists and antagonists on the
      phosphoinositide (PI) turnover response were investigated in the rat brain. The
      kappa-agonists U-50,488H and ketocyclazocine produced a concentration-dependent
      increase in the accumulation of IP's in hippocampal slices. The other kappa
      agonists Dynorphin-A (1-13) amide, and its protected analog D[Ala]2-dynorphin-A
      (1-13) amide also produced a significant increase in the formation of [3H]-IP's,
      whereas the mu-selective agonists [D-Ala2-N-Me-Phe4-Gly5-ol]-enkephalin and
      morphine and the delta-selective agonist [D-Pen2,5]-enkephalin were ineffective.
      The increase in IP's formation elicited by U-50,488H was partially antagonized by
      naloxone and more completely antagonized by the kappa-selective antagonists nor
      binaltorphimine and MR 2266. The formation of IP's induced by U-50,488H varies
      with the regions of the brain used, being highest in hippocampus and amygdala,
      and lowest in striatum and pons-medulla. The results indicate that brain kappa-
      but neither mu- nor delta-receptors are coupled to the PI turnover response.

PMID- 1975083
TI  - The influence of sodium omission on alpha 2-adrenergic inhibition of insulin
      release by mouse islets.
AB  - The mechanisms by which activation of alpha 2-adrenoceptors inhibits insulin
      release are still incompletely understood. This study, performed with isolated
      mouse islets, identifies a possible role of Na+ in this inhibition. Regardless of
      the stimulus used to induce insulin release, the inhibitory effect of low
      concentrations of clonidine (0.01-0.1 microM) was markedly smaller in the absence
      of Na+ (with choline or lithium as substitute) than in its presence. The
      effectiveness of a high concentration of clonidine (1 microM) was, however, not
      affected by Na+ omission. The results indicate either that Na+ omission
      indirectly counteracts an effect of clonidine (e.g. on a membrane permeability or
      on Ca2+ handling), or that Na+ is directly involved in a cellular process (e.g. a
      Na+ current or the Na+/H+ exchange) controlled by alpha 2-adrenoceptors.

PMID- 1975084
TI  - Noradrenergic mechanisms appear not to be involved in cocaine-induced seizures
      and lethality.
AB  - In the present study we have investigated the effects of compounds which increase
      synaptic levels of noradrenaline on cocaine-induced seizures and lethality in
      mice. The noradrenaline uptake blocker desipramine (0.3, 3, 30 mg/kg i.p.; 1h
      pretreatment) and the alpha 2-antagonists idazoxan (0.05, 0.5, 5 mg/kg i.p.; 15
      min) and RX811059A (0.01, 0.1, 1 mg/kg i.p.; 15 min) neither reduced nor
      increased the number of animals having convulsions in the 10 min following
      administration of cocaine (45, 60 mg/kg i.p.). None of these drugs increased
      lethality when assessed 10 minutes after 60 mg/kg cocaine and the alpha 2
      antagonists did not protect against the lethal effects of a 90 mg/kg dose. On the
      other hand, desipramine significantly reduced the number of animals dying after
      this high dose of cocaine. These results suggest that noradrenergic mechanisms do
      not promote cocaine-induced convulsions and lethality - an important observation
      in light of the growing use of desipramine for initiation of abstinence in
      cocaine-dependent outpatients.

PMID- 1975085
TI  - Integrity of Escherichia coli P pili during biogenesis: properties and role of
      PapJ.
AB  - The papJ gene of uropathogenic Escherichia coli is required to maintain the
      integrity of Gal alpha (1-4)Gal-binding P pili. Electron microscopy and ELISA
      have established that strains carrying the papJ1 mutant allele have a large
      amount of pilus antigen free of the cells. In contrast to the whole pili released
      by strains unable to produce the PapH pilus anchor, the free papJ1 pili consist
      of variably sized segments that appear to result from internal breakages to the
      pilus. The DNA sequence of papJ is presented and its gene product identified as
      an 18kD periplasmic protein that possesses homology with nucleotide-binding
      proteins. PapJ may function as a 'molecular chaperone' directly or indirectly
      establishing the correct assembly of PapA subunits in the P pilus.

PMID- 1975086
TI  - Probing beta-adrenergic receptors.

PMID- 1975087
TI  - The rabbit syndrome.

PMID- 1975088
TI  - Sequential activation of HOX2 homeobox genes by retinoic acid in human embryonal
      carcinoma cells.
AB  - RETINOIC acid had been implicated as a natural morphogen in chicken and frog
      embryogenesis, and is presumed to act through the gene regulatory activity of a
      family of nuclear receptors. Homeobox genes, which specify positional information
      in Drosophila and possibly in vertebrate embryogenesis, are among the candidate
      responsive genes. We previously reported that retinoic acid specifically induces
      human homeobox gene (HOX) expression in the embryonal carcinoma cell line NT2/D1.
      We now show that the nine genes of the HOX2 cluster are differentially activated
      in NT2/D1 cells exposed to retinoic acid concentrations ranging from 10(-8) to
      10(-5) M. Genes located in the 3' half of the cluster are induced at peak levels
      by 10(-8) M retinoic acid, whereas a concentration of 10(-6) to 10(-5) M is
      required to fully activate 5' genes. At both high and low retinoic acid
      concentrations, HOX2 genes are sequentially activated in embryonal carcinoma
      cells in the 3' to 5' direction.

PMID- 1975089
TI  - Change of tyrosine hydroxylase in the parkinsonian brain and in the brain of MPTP
      treated mice as revealed by homospecific activity.
AB  - Changes in homospecific activity (unit of enzyme activity per unit of enzyme
      protein; Rush, Kindler and Udenfriend, 1974. Biochem. Biophys. Res. Commun., 61,
      38) of tyrosine hydroxylase (TH) in the striatum of the brain were examined in
      MPTP-treated mice and parkinsonian patients. After a single injection of MPTP to
      mice, TH activity was acutely inhibited only in situ without changes in in vitro
      TH activity (Vmax) and TH protein; TH homospecific activity (TH Vmax/TH protein)
      did not change. After repeated injection of MPTP to mice for 8 days, in situ TH
      activity, in vitro TH Vmax, and TH protein were decreased in parallel, and TH
      homospecific activity did not change. The result indicates that the decreases in
      in situ TH activity and in TH Vmax are due to the decrease in TH protein by nerve
      degeneration of dopaminergic neurons in MPTP treated mice. However, when MPP+ was
      infused in the striatum of rats for 3 hours, in vitro TH activity (Vmax) was
      decreased without changes in TH protein. Thus, TH homospecific activity was
      decreased. The results indicate that MPP+ inactivates TH protein in the striatum
      after continued infusion. In contrast, the homospecific activity of Th in post
      mortem parkinsonian striatum was increased 3-fold. The increase in homospecific
      activity of residual TH in parkinsonian brain suggests such molecular changes in
      TH molecules as result in a compensatory increase in TH activity.

PMID- 1975090
TI  - [Modern view of the pathogenesis and therapy of gastroduodenal peptic ulcer].
AB  - After a wide analysis of peptic gastroduodenal ulcer medical therapy, before and
      after the era of cimetidine, the Authors, after a brief account of the Anatomy
      and Physiology of the stomach, examine surgical therapy, from the end of the last
      century till now. After giving the results of the surgical cases of one of them
      (A. Vinci), including 500 operations, from 1955 till now, almost all with gastric
      resection, without vagotomy, the Authors point out that today, in the era of
      cimetidine, surgical therapy has considerably diminished and is reserved only for
      the complications of pathological cases (perforation, hemorrhage, closed duodenum
      stenosis), and for those cases which don't respond to antisecretory
      pharmacological therapy. They also emphasize, that nowadays, in spite of the
      cooperation among gastroenterologists, gastroscopists and surgeons, the
      etiopathogenesis of peptic ulcer isn't clear yet, and they conclude by saying
      that our lack of knowledge of its origin and natural evolution, doesn't guarantee
      a definitive cure, although the therapy with cimetidine and similar medicines,
      according to the Authors' personal experiences and opinion, must be continued for
      the patient's entire life.

PMID- 1975091
TI  - Excitatory amino acid receptors and nociceptive neurotransmission in rat spinal
      cord.
AB  - Excitatory amino acid (EAA) receptor agonists were tested for their effect on
      identified rat spinal neurons. Only 75% of the spinal neurons tested increased
      their firing rate in response to iontophoretic application of one or more of the
      EAA receptor agonists, N-methyl-D-aspartate (NMDA), quisqualate (Quis), (RS)
      alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid HBr (AMPA), and kainate
      (KA). NMDA and Quis or AMPA activated primarily nociceptive neurons (60% of these
      neurons were projection neurons) in the rat spinal cord. KA-activated neurons
      were primarily classified as low threshold neurons. Both NMDA and AMPA, at
      subthreshold doses, significantly increased neuronal responses to peripheral
      noxious mechanical stimulation; NMDA also significantly increased neuronal
      responses to peripheral noxious thermal stimulation. Iontophoretically applied
      phencyclidine (PCP) decreased NMDA-induced firing in 100% of the cells tested
      while Quis-induced firing was blocked by PCP in only 33% of the cells tested. The
      reported analgesic effects of PCP in humans may result from a spinal action
      involving its well documented interaction with NMDA receptors.

PMID- 1975092
TI  - Fine mapping of the chromosome 11q22-23 region using PFGE, linkage and haplotype
      analysis; localization of the gene for ataxia telangiectasia to a 5cM region
      flanked by NCAM/DRD2 and STMY/CJ52.75, phi 2.22.
AB  - Using pulsed-field gel electrophoresis, and a range of different enzyme digests,
      we have established that both markers of each of the pairs CJ52.208/YNB3.12,
      NCAM/DRD2, and STMY/CJ52.75, on chromosome 11q22-23, show physical linkage on a
      single DNA fragment. We have also shown, using genetic linkage and haplotype
      analyses, that these markers lie within a region of approximately 18cM, which, it
      has been shown previously, is likely to contain the A-T gene. The relative
      positions of these marker loci, and the distance between them was determined in
      order to construct a detailed map which has allowed a more precise localization
      of the A-T gene. We have shown that in pairwise linkage analysis the strongest
      support for linkage to the A-T gene was with the STMY/CJ52.75 locus (Z = 5.59,
      theta = 0.0). A three-point analysis using the results from STMY/CJ52.75 and the
      closely linked marker phi 2.22 gave Z = 5.55, theta = 0.03. Despite persisting
      evidence of some linkage to Thy-1 our results are consistent with the existence
      of a single A-T locus on chromosome 11q22-23 and our best estimate of the
      position of this locus places it between NCAM/DRD2 and (STMY/CJ52.75, F2.22) (Z =
      6.74), a region of approximately 5cM in males.

PMID- 1975093
TI  - Molecular mechanisms underlying the expression of the human HOX-5.1 gene.
AB  - The complex mechanisms underlying homeobox genes expression involve regulation at
      transcriptional, post-transcriptional and translational levels. The multiple
      transcripts of the human HOX-5.1 gene are expressed differentially in tissue- and
      stage-specific patterns during embryogenesis, and differentially induced by
      retinoic acid (RA) in human embryonal carcinoma (EC) NT2/D1 cells. We have
      sequenced 6.3 Kb of the genomic region containing the HOX-5.1 gene and analyzed
      its mechanisms of expression. Two alternative promoters underlie the
      transcription of two classes of HOX-5.1-specific mRNAs. These classes differ in
      tissue and subcellular distribution, induction by RA, structure of the 5'-UT
      region and mRNA stability: these features are compatible with a differential
      function of the two classes of transcripts in embryogenesis.

PMID- 1975094
TI  - The lack of transcriptional activation of the v-erbA oncogene is in part due to a
      mutation present in the DNA binding domain of the protein.
AB  - Using a transient co-transfection system we have demonstrated that response
      elements for estrogen (ER), thyroid hormone (TR) and retinoic acid receptors
      (RAR) are closely related. Thyroid hormone-induced activation of transcription
      was observed in CV1 cells and not in HeLa cells, suggesting the existence of cell
      specific transcription factors necessary for the response. By contrast to its
      cellular counterpart (c-erbA/cTR alpha) the oncogene protein gag v-erbA is unable
      to activate gene transcription from different response elements derived from the
      rat growth hormone (rGH) gene promoter. A chimeric construct consisting of the ER
      in which the DNA binding domain has been replaced by that of cTR alpha was able
      to stimulate the reporter gene. In contrast, a construct in which ER DNA binding
      domain has been replaced by that of gag v-erbA did not activate gene
      transcription. These results lead us to the conclusion that the mutated DNA
      binding domain of v-erbA is in part responsible for the lack of transcriptional
      activation and in repression of gene expression. This is due in large part to the
      Gly73----Ser mutation which corresponds to the position of one of the three
      discriminating amino acids that are thought to interact with a specific base of
      the response element.

PMID- 1975095
TI  - The 3' ends of alu repeats are highly polymorphic.

PMID- 1975096
TI  - Prenatal detection of an Arg----Ter mutation at codon 111 of the PAH gene using
      DNA amplification.
AB  - A CGA----TGA mutation at codon 111 in exon 3 of the phenylalanine hydroxylase
      (PAH) gene was recently identified in a Chinese phenylketonuria (PKU) patient.
      This paper reports the prenatal diagnosis of a Chinese fetus at risk for PKU
      using DNA amplification with PCR and oligonucleotide hybridization. RFLP analysis
      revealed that the fetus had inherited a PKU gene from his mother, but his
      paternal PAH gene was uninformative. PCR amplification of 300 bp which included
      exon 3 plus the flanking intronic sequences of the PAH gene was performed. The
      amplified DNA was hybridized with a pair of allele-specific oligonucleotide
      probes. The results indicated that the fetal DNA carried a PAH 111 Arg----Ter
      mutant gene inherited from his father. Thus, the fetus was predicted to be
      affected with PKU.

PMID- 1975097
TI  - Thyrotropin-releasing hormone-degrading enzyme in human serum is classified as
      type II of pyroglutamyl aminopeptidase: influence of thyroid status.
AB  - The characteristics of thyrotropin-releasing hormone (TRH)-degrading enzyme in
      human serum were studied. Serum was incubated in 0.1 M phosphate buffer
      containing [proline-3H]TRH at 37 degrees C. A thin layer chromatography analysis
      of TRH degradation did not show any radioactive peak located in an acid TRH
      position, but apparent radioactive peaks corresponding to His-Pro and His-ProNH2
      occurred in the presence of p-hydroxymercuriphenyl sulfonic acid, an inhibitor of
      proline dipeptidase. With ion exchange paper chromatography, the formation of 3H
      labeled His-Pro and His-ProNH2 was estimated as an end point in the measurement
      of pyroglutamyl aminopeptidase (pGlu-peptidase) activity. An assay using p
      hydroxymercuriphenyl sulfonic acid was developed to sensitively quantitate the
      pGlu-peptidase. Neither bacitracin nor p-chloromercuribenzoic acid increased the
      activity of pGlu-peptidase. The addition of EDTA, dithiothreitol, and o
      phenanthroline significantly inhibited pGlu-peptidase activity, but neither
      iodoacetamide nor ethylmaleimide altered its activity. The pGlu-peptidase had a
      stereotypic specificity for the tripeptide, pGlu-His-ProNH2 of TRH, and its Km
      was 44.9 microM. The pGlu-peptidase activity was not changed by either hyper- or
      hypothyroidism. The present data indicate that a TRH-degrading enzyme in human
      serum possesses a nature identical to type II of pGlu-peptidase which is not
      altered by thyroid status.

PMID- 1975099
TI  - The effects of somatostatin and somatostatin antiserum on the retention of
      passive avoidance behavior after neofrontal decortication in rats.
AB  - Rats were tested for passive avoidance behavior in a one-trial step-through
      learning paradigm. After the learning trial, the animals underwent neofrontal
      decortication or sham operation. On the 8th day after operation, the lesioned or
      sham-operated rats received intracerebroventricular (ICV) injections of
      somatostatin (SST; 4 micrograms/2 microliters) or somatostatin antiserum (SST-AB;
      2 microliters) 1 hr before the retention test. Decortication alone decreased the
      latency in comparison to that in the sham-operated group, and ICV treatment did
      not influence this impairment. After treatment with SST-AB the latency decreased,
      indicating that endogenous SST may play a role in the maintenance of normal
      memory processes.

PMID- 1975098
TI  - DNA-damage-inducible genes in mammalian cells.

PMID- 1975100
TI  - [Plasma anticholinergic activity and cognitive function in geriatric patients].
AB  - This study evaluated the putative impact of circulating anticholinergic
      equivalents on cognitive functional performance in non-demented geropsychiatric
      inpatients. Standard rating instruments were administered to measure memory
      functions, concentration and overall functional competency. Anticholinergic
      plasma activity was assayed, using a radioreceptor technique with tritiated
      quinuclidinyl benzilate as the active reagent. None of the cognitive tests
      employed indicated a statistically significant change in the subjects'
      quantifiable level of cognitive performance. All changes in anticholinergic
      activities were related to adjustments in psychotherapeutic medications. The
      possible role of reversal of pseudodementing features is discussed as well as the
      potential for monitoring anticholinergic activity when treating elderly
      individuals with more than one centrally active medication having anticholinergic
      properties.

PMID- 1975101
TI  - Prolactin shifts after neuroleptic withdrawal.
AB  - Neuroleptic-induced alterations in serum prolactin levels may have important
      clinical implications. Twenty-two stable schizophrenic patients, taken off
      medication over a 3-week period, were followed for 40 weeks or until the
      neuroleptic was reinstituted. Serum prolactin levels were measured during
      neuroleptic treatment and during the neuroleptic-free period. When serum
      prolactin levels were plotted over time, 55% of the subjects showed shifting
      prolactin levels in the shape of a "V" (i.e., a fall in prolactin level preceding
      an increase in the level) in the early weeks following withdrawal. Subjects with
      the "V" shape had significantly lower prolactin levels during neuroleptic
      treatment than those without the "V" shape. The pathophysiological significance
      of the prolactin "V" pattern is uncertain. It is consistent, however, with
      transient dopaminergic hyperactivity following neuroleptic withdrawal.

PMID- 1975102
TI  - RFLP alleles at the tyrosine hydroxylase locus: no association found to affective
      disorders.
AB  - Affective disorders are usually referred to as being inherited multifactorially.
      The contribution of a gene locus in illnesses displaying multifactorial
      inheritance may be assessed by searching for associations of alleles to the
      illness. The tyrosine hydroxylase gene encodes the rate-limiting enzyme in the
      synthesis of catecholamines and might be a candidate for causing the manic
      depressive phenotype. Therefore, we tested 88 patients with affective disorders
      and 99 healthy control persons for association of restriction fragment length
      polymorphism (RFLP) alleles at the tyrosine hydroxylase locus. The comparison of
      allele or genotype frequencies did not reveal any significant differences between
      the two groups.

PMID- 1975103
TI  - Neuroleptic effects on interhemispheric and intrahemispheric performance of
      tactile discrimination tasks by schizophrenic patients.
AB  - The contribution of neuroleptic medication to impaired interhemispheric
      integration of information, and the relationship between the apparent
      interhemispheric failure and a unilateral dysfunction, were examined in 12
      acutely psychotic patients. The patients performed tactile discrimination tasks,
      under conditions of intrahemispheric and interhemispheric presentation, before
      the introduction of any antipsychotic medication, and again after a period of
      treatment with neuroleptics. In unmedicated patients, both unilateral left
      hemispheric and interhemispheric deficits were found. However, whereas treatment
      with neuroleptics normalized the unilateral left hemispheric deficit, it did not
      have any effect on the performance of the interhemispheric tasks. These findings
      suggest that the impairment in interhemispheric integration is independent of the
      unilateral dysfunction and is not modulated by treatment with neuroleptics.

PMID- 1975104
TI  - Spontaneous orofacial movements induced in rodents by very long-term neuroleptic
      drug administration: phenomenology, pathophysiology and putative relationship to
      tardive dyskinesia.
AB  - While understanding of the major clinical and ethical issue of tardive dyskinesia
      would be greatly facilitated by the development of an isomorphic or homologous
      animal model, particularly in rodents, this has proved to be a highly contentious
      issue. The literature on orofacial function in rats administered neuroleptic
      drugs for substantial proportions of their adult lifespan is reviewed. It reveals
      the emergence of late-onset orofacial movements in a number of studies, but very
      early-onset movements or no effect in others. Potential explanations for these
      discrepancies are considered, and ways of resolving such inconsistencies are
      suggested. The relationship of these various orofacial phenomena to dopaminergic
      and non-dopaminergic function, and to clinical syndromes, is critically
      evaluated.

PMID- 1975105
TI  - A possible role of AA2 excitatory amino acid receptors in the expression of
      stimulant drug effects.
AB  - GDEE, an antagonist of the AA2 or quisqualic acid category of excitatory amino
      acid receptor, decreases behavioral activity and locomotor stimulation induced by
      cocaine and amphetamine when locally injected into the nucleus accumbens. The
      present experiment was intended to examine the effects of systemic GDEE and other
      excitatory amino acid antagonists on stimulant-induced locomotor activity. GDEE
      markedly attenuated the stimulant effect of amphetamine, and partially blocked
      the effects of phencyclidine (PCP). Apomorphine-induced cage climbing behavior
      was partially decreased by lower dosages of GDEE, but was almost completely
      blocked by the highest dosage tested. Amphetamine-induced stimulation of
      locomotor activity was not decreased by any of the other excitatory amino acid
      antagonists that were tested, including MK-801, 2-amino-7-phosphonoheptanoic acid
      (APH), or CNQX. APH decreased stereotypy only at a high dosage (250 mg/kg), which
      also produces ataxia. Several other compounds, including L-glutamic acid gamma
      ethyl ester (GMEE), L-glutamic acid, glycine, and L-glutamine did not block
      amphetamine-induced stimulation in molar dosages equivalent to the highest dosage
      of GDEE (8 mmol/kg). It is concluded that the AA2 excitatory amino acid receptor
      is important in the expression of activating effects of stimulant drugs.

PMID- 1975106
TI  - Evidence for feeding elicited through antihistaminergic effects of tricyclic
      antidepressants in the rat hypothalamus.
AB  - We studied central mechanisms of antidepressants that affect feeding behavior in
      rats. The tricyclic compounds amitriptyline, doxepin and imipramine significantly
      induced feeding after their infusion into the third cerebral ventricle in the
      light phase, but the tricyclic, desipramine, and the dicyclic zimelidine, did
      not. Drinking was not affected by any compound tested. The relative order of
      potency in eliciting feeding was: amitriptyline and doxepin greater than
      imipramine greater than desipramine and zimelidine. To clarify the involvement of
      neuronal histamine in antidepressant-induced feeding, alpha-fluoromethylhistidine
      (FMH), a "suicide" inhibitor of histidine decarboxylase, was intraperitoneally
      administered before infusion of amitriptyline. FMH attenuated the amitriptyline's
      effect. Bilateral microinfusion of amitriptyline into the ventromedial
      hypothalamus or the paraventricular nucleus verfied that these are loci for the
      modulation of feeding by amitriptyline. In the lateral hypothalamus,
      amitriptyline was less effective. These findings indicate that tricyclic
      antidepressants directly facilitate feeding, which is, at least in part, mediated
      by histamine in the hypothalamus.

PMID- 1975107
TI  - Antidepressant-like activity of 5-HT1A agonists measured with the forced swim
      test.
AB  - This study examined the abilities of 5-hydroxytryptamine (5-HT) agonists with
      varying selectivity for different subtypes of 5-HT receptors to produce
      antidepressant-like behavioral effects in the forced swim test in rats. The 5
      HT1A agonists 8-OH-DPAT (0.125-1.0 mg/kg, SC) and tandospirone (SM-3997) (5-20
      mg/kg, SC) both produced dose-related decreases in immobility time following
      subchronic treatment in rats. These effects were similar to those of the
      tricyclic antidepressants imipramine (5-15 mg/kg) and desipramine (5-15 mg/kg).
      In addition, the 5-HT1A agonists, buspirone (20 mg/kg), gepirone (20 mg/kg) and
      ipsapirone (10 and 20 mg/kg) demonstrated antidepressant-like effects. Other
      groups of rats treated subchronically with each of the 5-HT1A agonists or
      antidepressants showed no increase in locomotor activity, so that general changes
      in activity could not account for the reduction of immobility time in the forced
      swim test. 5-HT agonists selective for other receptor subtypes, such as the 5
      HT1B/1C agonist m-CPP (5 mg/kg) and the 5-HT2/1C agonist DOB (1 mg/kg), were not
      effective in this behavioral test. The benzodiazepine diazepam (5 mg/kg) also
      failed to reduce immobility time, suggesting that anxiolytic properties of 5-HT1A
      agonists did not mediate this behavioral effect. A common metabolite of some of
      the 5-HT1A agonists, 1-PP, was ineffective in reducing immobility time. The
      stimulant d-amphetamine (2 mg/kg) significantly reduced immobility time but also
      significantly increased locomotor activity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1975108
TI  - A theory of benzodiazepine dependence that can explain whether flumazenil will
      enhance or reverse the phenomena.
AB  - Repeated administration of benzodiazepines (BDZs) produces dependence in man and
      animals and this is reflected in the phenomena of tolerance and withdrawal
      responses. In BDZ-dependent animals the BDZ-receptor antagonist flumazenil (Ro 15
      1788) reverses the increased anxiety and decreased seizure threshold seen when
      benzodiazepine treatment is withdrawn. In contrast are reports that flumaenil
      enhances BDZ-withdrawal responses. Indirect influences on the direction of
      flumazenil's effects on anxiety are the duration and dose of BDZ treatment,
      whether tolerance has developed to its anxiolytic effect and whether there is an
      anxiogenic response on drug withdrawal. However, we conclude that the crucial
      factor is the anxiety level of the animal: when this is high flumazenil becomes
      anxiolytic; when this is low flumazenil is anxiogenic. These bidirectional
      effects of flumazenil can be seen in drug-naive and BDZ-dependent animals. We
      propose a theory of benzodiazepine dependence that can account for anxiogenic
      responses on drug withdrawal and for flumazenil's bidirectional effects; central
      to this theory is the assumption that flumazenil normalises the benzodiazepine
      receptor, returning it to a baseline state. Thus it is whether an animal's score
      lies above or below this baseline that will determine the direction of
      flumazenil's effect. The clinical implications of this theory are discussed. We
      suggest that during the development of benzodiazepine dependence, two independent
      adaptive biochemical mechanisms are triggered: one underlying the development of
      tolerance to the anxiolytic responses, the other underlying the incidence of
      increased anxiety on drug withdrawal. It is only changes in the latter that are
      induced by the administration of flumazenil.

PMID- 1975109
TI  - Imaging of the foot and ankle.
AB  - The foot and ankle are subjected to daily stresses and strains ranging from
      normal walking activities to the excessive forces encountered in the active
      sports enthusiast. These traumatic events as well as systemic and local arthritic
      conditions and tumors can be temporarily or permanently disabling. Early,
      expedited, and cost-efficient diagnosis is the daily challenge for the
      radiologist, clinician, and patient.

PMID- 1975110
TI  - Importance of treating anxiety in the elderly ill patient.

PMID- 1975111
TI  - Panic disorder: integrating psychotherapy and psychopharmacology.

PMID- 1975112
TI  - Wrestling with allergies.

PMID- 1975113
TI  - [Evaluation of the degree of muscle blockade: a comparative study using
      electromyography of the muscular relaxation induced by pancuronium, atracurium
      and vecuronium].
AB  - To compare the muscle relaxing effect of pancuronium, atracurium and vecuronium,
      99 patients operated on under neuroleptanesthesia were divided in three groups
      depending on whether they had received, during induction, pancuronium 0.1 mg/kg,
      atracurium 0.5 mg/kg, or vecuronium 0.1 mg/kg. One-fourth of the initial dose was
      repeated if necessary. The electromyographic study of the muscle relaxing effect
      was carried out with stimulation of the cubital nerve with courses of
      supramaximal square wave electric stimuli in 'trains of four'. The time to
      maximal blockade (TMB), the time of clinical effectiveness (TCE), the total
      duration time (TDT), the time of duration of the maintenance dose (DM 25) and the
      recovery index (RI) were measured. TMB was 4.3 +/- 1 min for pancuronium, 3.5 +/-
      0.8 min for atracurium, and 3.3 +/- 0.98 min for vecuronium. The differences
      between pancuronium and the other drugs were statistically significant, but they
      were not so between the latter two. TCE was 67.9 +/- 13.5 min for pancuronium,
      significantly longer than with vecuronium and atracurium (28.2 +/- 5.7 and 31.5
      +/- 4.7, respectively). TDT was 126.2 +/- 19.9 min for pancuronium, 61.2 +/- 11.5
      min for atracurium and 55.5 +/- 16.7 for vecuronium. The mean duration of the
      repeated dose was 52.7 +/- 8.4 min for pancuronium, 19.9 +/- 5 min for vecuronium
      and 10.9 +/- 5 min for atracurium. RI, which was similar for atracurium and
      vecuronium (12.7 +/- 1.7 min and 12.8 +/- 3.3 min), was longer for pancuronium
      (27.7 +/- 4.3 min).

PMID- 1975114
TI  - [Effectiveness of somatostatin in the treatment of acute upper digestive
      hemorrhage].
AB  - Our study has been made on a retrospective basis in order to evaluate the
      efficacy of somatostatin (SST) in the treatment of acute haemorrhage caused by
      gastroduodenal ulcer. Sixty patients were allocated in 2 groups: those who
      received SST (n = 30), and those who did not received it (n = 30), and were
      treated only with conventional measures (nasogastric catheter, H2 blockers, blood
      or derivatives, etc.). Both groups were monitored and controlled at the
      Anesthesia-Intensive Care Unit. The patients in the SST group received a
      continuous intravenous infusion of 250 micrograms/h. These patients showed better
      hemodynamic parameters, and only seven needed surgery. The patients in the
      conventional treatment group showed worse hemodynamics, needed higher volumes of
      hemoderivatives, and 25 of them needed surgery. The statistical analysis of our
      data supports the efficacy of SST in the treatment of uncontrollable upper
      gastrointestinal bleeding due to gastroduodenal ulcer.

PMID- 1975115
TI  - Marked shortage of C4B DNA polymorphism among insulin-dependent diabetic
      patients.
AB  - TaqI, BamHI and HinddIII polymorphisms of the C4 genes were studied with a 500-bp
      C4 cDNA probe (pAT-A153) specific for the 5' end of the gene. The restriction
      patterns obtained were correlated with the C4A and C4B genotypes in 35 patients
      suffering from insulin-dependent diabetes mellitus (IDDM), and results were
      compared to those from 40 healthy individuals. The controls, all Caucasian, were
      genotyped for HLA-A, B, C, DR, Bf, C2 and C4, together with 10 diabetics and
      their families; haplotypes for the other patients had been deduced using DNA and
      protein polymorphism, and taking into consideration linkage disequilibrium for
      neighbouring loci. No significant difference between genotypes at the C4A locus
      was seen in either population. The C4A gene deletion, associated with a C4B
      "short" gene (66.7%), was found mainly in the haplotype B8,Cw7,DR3,BfS,C2C,
      C4AQOB1, and the C4B gene deletion in the haplotype B18,Cw5,DR3,BfF1,
      C2C,C4A3BQO. When diabetic patients were compared with normal individuals, we
      observed, at the C4B locus, a decrease in the C4B "long" gene (22% vs. 49%
      respectively, p less than 0.001). A compensatory increase was observed in
      patients vs. controls for the frequency of C4BQO, both in the deleted and intact
      form (26% vs. 10% respectively, p less than 0.03).

PMID- 1975116
TI  - [Clinical significance of urinary enzymes in diabetes mellitus].
AB  - The aim of this study was to clarify the clinical significance of urinary enzyme
      activity in patients with diabetes mellitus. Patients were divided into two
      groups: group A - 102 outpatients, group B-23 inpatients. Spot urine samples
      before breakfast from group A and aliquots of 24-hours urine collections at 4
      degrees C from group B were used. Urinary enzyme activities (N-acetyl- beta-D
      glucosaminidase: NAG, alkaline phosphatase: ALP, leucine aminopeptidase: LAP,
      gamma-glutamyl transpeptidase: gamma-GTP) were determined by spectrophotometric
      assay, rate assay, Tuppy method and Orlowski method, respectively. 1) In group A,
      the percentage of the cases which showed higher than the normal range (NAG: 1.3
      8.7, ALP: 4.2-17.7, LAP: 0-22.9 U/g. cer.) was 42.2% in NAG, 21.6% in ALP, and
      8.8% in LAP. In a multiple regression analysis, the predictor variables which
      contributed to NAG were HbA1c, age, urinary protein and the one that contributed
      to ALP, LAP, gamma-GTP was urinary beta 2-microglobulin. 2) In group B, 87% of
      NAG was above the normal range (Mean +/- 2 SD; 4.8 +/- 3.9 U/day). There was no
      difference in the NAG activity between patients with and without nephropathy. The
      percent of high activities of ALP, LAP and gamma-GTP were 17%, 17%, 4%,
      respectively. Most of them were patients with nephropathy. There were
      correlations among ALP, LAP and gamma-GTP, though no correlation existed between
      NAG and the other three enzymes. These results suggested: 1) NAG reflects
      lysosomal dysfunction of both glomerular and proximal tubular epithelial cells
      which may be caused by poor glycemic control.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1975117
TI  - [Psychiatric symptom dimensions induced by work stress--an application of
      redundancy analysis].
AB  - The relationship between work stress estimated by a work stress questionnaire and
      several psychic symptoms estimated by a psychiatric symptom questionnaire was
      examined by redundancy analysis, which is a multivariate statistical technique to
      determine two sets of variables, one set being dependent on the other. Its aim is
      maximization of the explained variance of the dependent variables by the linear
      combination of the explanatory variables. The results showed that the depressive
      items had the largest loadings on the work stress variables, when the psychiatric
      symptom questionnaire was used as dependent variable and that the dullness
      dimension and the concentration difficulty dimension tended to have high
      loadings, when the same analysis was done using the subjective fatigue feeling
      questionnaire and the work stress questionnaire. We ascertained that these two
      fatigue symptom dimensions, especially the latter, are identical with the
      depression dimension in the psychiatric questionnaire. We concluded that work
      stress might induce a depressive state rather than other psychological or
      psychiatric states.

PMID- 1975119
TI  - The presence of infectious virus but not conventional antigen can exacerbate
      graft-versus-host reactions.
AB  - Previous reports have demonstrated that the introduction of virus (MCMV, HSV-1)
      concurrent with a graft-versus-host reaction (GvHR) limited to a class I MHC
      disparity can result in the enhancement of GvHR-associated phenotypic (changes in
      CD4/CD8 ratio) and functional (inability to produce secondary antibody responses)
      alterations including the augmentation of in situ natural killer (NK) and donor
      anti-host cytotoxic T-cell activity. In the present study, we investigated
      whether immunogens other than infectious virus may be capable of enhancing GvHR.
      Mice receiving donor cells and the T-dependent antigen dinitrophenyl-bovine serum
      albumin (DNP-BSA) did not display exacerbated GvHR as evidenced by the absence of
      phenotypic alterations and the absence of elevated NK activity and the lack of
      donor anti-host cytotoxic activity. Furthermore, these recipients produced normal
      levels of IgM and IgG anti-DNP antibody. In addition, mice which received
      ultraviolet light (UV)-inactivated virus (even at 100 x dosage) together with
      donor cells also did not exhibit exacerbated GvHR. In total, these findings
      illustrate a novel ability of infectious virus to exacerbate GvH reactions and
      are consistent with the hypothesis that viral-induced immune responses may be
      important in the ability of a pathogen to induce the development of severe GvHR.

PMID- 1975118
TI  - Human natural killer clones enhance in vitro antibody production by tumour
      necrosis factor alpha and gamma interferon.
AB  - To determine whether NK cells are involved in the regulation of the antibody
      response, we studied the effects of human NK clones on B-cell growth and
      differentiation and the mechanisms involved. We demonstrate that various human NK
      clones enhance the immunoglobulin production of SAC/rIL-2-activated B cells, e.g.
      IgG and IgM by up to 230% and anti-tetanus toxoid antibodies by up to 430%. Cell
      cell interactions via cell-surface structures, e.g. the CD11a/CD18 molecule, were
      found to be critical. Subsequently the NK-mediated B-cell regulation involves
      cytokines, since cell-free supernatants obtained by 48-h cultures of NK clones
      exerted BCGF and BCDF activity. Neutralization studies and direct determination
      characterized these cytokines as IFN-gamma and TNF-alpha. The cytokine production
      of NK clones could be triggered by activated B cells only. Northern blot analysis
      demonstrated that activated B cells in co-culture with NK clones were able to
      induce accumulation of mRNA transcripts for IFN-gamma and TNF-alpha in NK cells.

PMID- 1975120
TI  - Principles of evaluation and results in microsurgical treatment of major limb
      amputations. A follow-up study of 26 consecutive cases 1978-1987.
AB  - A total of 26 microvascular extremity replantations/revascularizations with a
      survival rate of 85% were followed for an average of 4.5 years. The material
      consisted of 11 upper arms, 11 lower arms, 1 wrist and 3 feet. In this
      comparatively small and inhomogenous material there was no significant influence
      found on the functional results regarding level of amputation, time of ischaemia
      or age of the patients. Sharp injuries had the best outcome. The functional
      results were evaluated following the principles outlined by Chen & Yu and by
      Tamai. Good and excellent results were found in 63% of the upper extremities
      according to these classifications and in 47% according to our own
      classification. Some of the difficulties in establishing indications and
      contraindications to replantation are outlined. To facilitate comparison of
      materials a modified and more realistic version of the score system of Tamai is
      recommended as a standard for evaluation of functional results following above
      wrist-replantation. This will enable early detection of progress in the treatment
      of extremity amputations.

PMID- 1975121
TI  - [Anesthesia by injection of xylazine, ketamine and the benzodiazepine derivative
      climazolam and the use of the benzodiazepine antagonist Ro 15-3505].
AB  - 25 horses which entered the clinic for minor surgery, received ketamine (2.2
      mg/kg i.v.) for induction of anesthesia after previous sedation with xylazine
      (1.1 mg/kg i.v.). As soon as the horses were in the lateral recumbency, the
      benzodiazepine derivate climazolam was administered at a dose of 0.1 mg/kg i.v.
      (10 horses) or 0.2 mg/kg i.v. (15 horses). The anesthesia was maintained with
      repeated injections of ketamine (1.1 mg/kg i.v. every 9-12 minutes). At the end
      of the surgery, 20 minutes after the last ketamine injection, Ro 15-3505, a
      benzodiazepine antagonist, was injected at a dose of 0.01 mg/kg i.v. or 0.02
      mg/kg i.v. Climazolam successfully suppressed the adverse reactions of ketamine,
      such as poor muscle relaxation, hyperacusis and convulsions. The benzodiazepine
      antagonist Ro 15-3505 allowed good control of the duration of anesthesia and--in
      most cases--a smooth, predictable recovery period was the result.

PMID- 1975123
TI  - Biological monitoring--consider the alternatives.

PMID- 1975122
TI  - Autoradiographic imaging of phosphoinositide turnover in the brain.
AB  - With [3H]cytidine as a precursor, phosphoinositide turnover can be localized in
      brain slices by selective autoradiography of the product [3H]cytidine diphosphate
      diacylglycerol, which is membrane-bound. In the cerebellum, glutamatergic
      stimulation elicits an increase of phosphoinositide turnover only in Purkinje
      cells and the molecular layer. In the hippocampus, both glutamatergic and
      muscarinic cholinergic stimulation increase phosphoinositide turnover, but with
      distinct localizations. Cholinergic stimulation affects CA1, CA3, CA4, and
      subiculum, whereas glutamatergic effects are restricted to the subiculum and CA3.
      Imaging phosphoinositide turnover in brain slices, which are amenable to
      electrophysiologic studies, will permit a dynamic localized analysis of
      regulation of this second messenger in response to synaptic stimulation of
      specific neuronal pathways.

PMID- 1975124
TI  - Development and application of biomarkers exploitable for human exposure
      monitoring.
AB  - The objectives, applications and limitations of laboratory methods for assessing
      human exposure to carcinogens are concisely discussed. The available technologies
      include cytological, cytogenetic and molecular analyses, somatic cell mutation,
      carcinogen-DNA or carcinogen-protein adducts, metabolic markers, and chemical or
      biological analyses of expired air, body fluids, and excreta.

PMID- 1975125
TI  - Cytogenetic surveillance of workers exposed to genotoxic chemicals: preliminary
      experiences from a prospective cancer study in a cytogenetic cohort.
AB  - Cytogenetic endpoints, conventionally chromosomal aberrations, and later sister
      chromatid exchanges and micronuclei have long been used to assess exposure of
      human populations to genotoxic agents. Although the adverse nature of somatic
      chromosome damage is recognized at the group level, no ill-health manifestations
      have been causally related to cytogenetic damage at the individual level. In work
      related exposures, e.g., ethylene oxide, styrene, benzene, vinyl chloride, and
      alkylating anticancer agents have been shown to induce somatic chromosomal damage
      in several studies. For all of these, a carcinogenic risk to humans has also been
      documented. The possible association of somatic chromosome damage and cancer will
      be elucidated in a Nordic prospective study. The objective is to find out the
      significance of a high or low score in any of the cytogenetic parametres to risk
      of cancer. In the Finnish part of the cohort of 806 individuals, 10 cases of
      cancer were observed during the first follow-up period. Although the cohort is
      young and the numbers small, a slightly significant (P = 0.04) trend was observed
      for individuals with cancer and a score of chromosomal aberrations. No trend was
      observed for sister chromatid exchanges. The application of cytogenetic
      surveillance is still not routine methodology, but it is useful and informative
      in carefully controlled study designs. Special efforts should be directed toward
      combining different disciplines, i.e., cytogenetics, adduct monitoring, and end
      effect epidemiology, in order to reach quantitativeness in risk assessment.

PMID- 1975126
TI  - 32P-postlabeling of 7-methylguanine adducts in DNA.
AB  - The 32P-postlabeling technique introduced by Randerath and co-workers has been
      particularly successful with stable and nonpolar DNA adducts, but the assay has
      not been used to any large extent to detect 7-alkylguanine derivatives. In the
      present communication, we have investigated the phosphorylation reaction by T4
      polynucleotide kinase using 7-methyl-3'-dGMP, ring-opened 7-methyl-3'-dGMP and
      enzyme-digested methylated DNA as substrates. The methylated substrates were
      detected at femtomol (fmol) sensitivities. 7-methyl-3'-dGMP was quantitatively
      phosphorylated at these low concentrations. The efficiency of phosphorylation of
      the ring-opened product was less. It was shown that ring-opened 7-methyl-3'-dGMP
      was resistant to digestion with nuclease P1, making alkali-treatment and enzyme
      digestion of DNA possible approaches to the determination of 7-methylguanine in
      DNA.

PMID- 1975127
TI  - Biochemical epidemiology: uses in the study of human carcinogenesis.
AB  - The use of biochemical markers may improve the potentialities of etiologic
      epidemiology. Exposure markers or markers of biologically effective dose allow
      better exposure assessment, therefore decreasing misclassification in
      epidemiological studies. Markers of individual susceptibility (such as metabolic
      polymorphism) permit the identification of subgroups of subjects at higher risk
      of cancer. In general, the integration of biochemical methods and an
      epidemiological design is helpful in the study of the sources of interindividual
      variability in response to carcinogenic stimuli. We review several investigations
      making use of biochemical measurements in the field of cigarette-induced bladder
      cancer.

PMID- 1975128
TI  - International symposium on strategies for the control of mutagenic and
      carcinogenic risk: current status and perspectives, Friday, May 5, 1989, Bologna.
AB  - The 18 posters, grouped under mutagenicity testing, metabolic activation,
      mechanisms of mutation and chromosome damage, human monitoring and safety are
      critically discussed. It is pointed out that rather than applying a single test,
      a battery of well-validated in vitro and in vivo tests is required. As a testing
      strategy, the one developed by Ashby is briefly mentioned. The value of the
      Salmonella assay and of in vitro cytogenetics as short term tests for detecting
      carcinogens, and of the bone marrow micronucleus test as one for assessing germ
      cell mutagenesis is pointed out. Various assays now available for measuring gene
      mutations in human lymphocytes and erythrocytes are briefly described. Since we
      have a considerable data-base for germ cell mutations in the mouse and data are
      now being collected for mutations in human somatic cells, the importance of
      studies on mutation induction in somatic cells of the mouse is emphasized. Such
      data on mouse somatic cells will help to define with greater precision mutation
      induction to be expected in human germ cells; that is genetic risks in humans on
      the basis of a "parallelogram-like" extrapolation using somatic mutations in man
      and germ cell mutations in the mouse can now be calculated.

PMID- 1975129
TI  - Cytotoxicity, anchorage-independent growth, and DNA adduct formation in human
      neonatal fibroblasts by 1,2,3,4-tetrahydro-7,12-dimethylbenz(a)-anthracene (TH
      DMBA), its six aryl fluoro regioisomers, and an exo methylene tautomer.
AB  - 1,2,3,4-Tetrahydro-7,12-dimethylbenz(a)anthracene (TH-DMBA), its six possible
      fluorosubstituted regioisomers, and the C-7 exo methylene tautomer of the 11F
      derivative have been investigated for their cytotoxicity and for their ability to
      induce anchorage-independent growth and to form adducts in human neonatal
      foreskin fibroblasts. All compounds tested exhibited a low level of cytotoxicity,
      determined as percent cloning efficiency, up to a final concentration of 30
      micrograms/ml. Except for 5F-TH-DMBA and the C-7 exo methylene tautomer, all
      compounds induced anchorage-independent growth of neonatal foreskin fibroblasts
      in soft agar at all concentrations tested (1, 3, 10 and 30 micrograms/ml). The C
      7 exo methylene tautomer induced anchorage-independent growth only at a
      concentration of 10 micrograms/ml. Among the compounds tested the 6F derivative
      was the most effective compound at 1 microgram/ml. The D-ring fluoro isomers
      induced anchorage-independent growth at a frequency comparable to TH-DMBA itself,
      with the 11F derivative being the least effective of the four D-ring
      regioisomers. All compounds except 5F-TH-DMBA formed detectable adducts with
      cellular DNA as determined by 32P postlabeling procedures, when the cells were
      treated at 1 microgram/ml. Two adducts were detected in cells treated with TH
      DMBA and four adducts were detected in DNA obtained from cells treated with 6F-TH
      DMBA. The level of bonding for the D-ring fluoro isomers was quantitatively less
      and sometimes qualitatively different than that for TH-DMBA. For the D-ring
      compounds, the ability to induce anchorage-independent growth frequency
      correlated with the total quantity of adduct formed. The C-7 exo methylene
      tautomer formed a single adduct and the level of bonding was less than one adduct
      per 10(9) nucleotides. Analysis of these results led to the proposal that the
      planar anthracene ring structure (rings B, C, and D) of TH-DMBA and possibly
      oxidative metabolism at benzylic carbon 4 of the A-ring are important to DNA
      bonding and initiation of induction of anchorage-independent growth.

PMID- 1975130
TI  - Dimethylsulfoxide as modifier of the organospecific mutagenicity of metronidazole
      in mice.
AB  - Mutagenicity and carcinogenicity of metronidazole (MT) are imputable to the
      formation of toxic intermediates, which include radical forms derived from the
      nitroreductive process. Since dimethylsulfoxide (DMSO), the "universal" solvent,
      can quench free radicals in vitro, it was suggested that DMSO might protect by
      scavenging free radical generation in vivo. This study wanted to evaluate if DMSO
      (given concomitantly or prophylactically) protects against the organospecific
      mutagenicity of MT in vivo by means of the intrasanguineous host-mediated assay.
      DMSO used as solvent showed a 20%-30% reduction in the mutation frequencies by
      MT. Prophylactic administration of DMSO for 3 d caused a suppression of the
      organospecific mutagenicity. However, some increases in the spontaneous mutation
      frequency and enhancement of MT mutagenicity in kidney were observed. The
      protective effect was paralleled by a decrease in NADPH cytochrome c (P450)
      reductase in liver, kidney, and to a lesser extent in lung microsomes from
      pretreated mice. Inhibition of mutagenic activity might be related to scavenging
      of radical species as supported by the lack of tissue specificity and no
      appreciable changes in specific enzyme activity. However, changes in reductase
      content in prophylactically pretreated mice can affect the quantitative
      biotransformation of MT to the proximal mutagen contributing to the observed
      suppression in mutation frequencies.

PMID- 1975131
TI  - Micronuclei assay in cytokinesis-blocked binucleated and conventional
      mononucleated methods in human peripheral lymphocytes.
AB  - Studies were performed to determine the genotoxic effect of cytochalasin-B (CYB)
      and to compare the efficacy of the cytokinesis-blocked binucleated cells (CB) for
      scoring micronuclei (MN) with the conventional mononuclear method, following
      treatment with mitomycin C and cyclophosphamide. The results show that 3-4
      micrograms/ml of CYB induced maximum number of binucleated cells without any
      genotoxic effect and the frequency of MN in binucleated cells was higher than
      that in the mononucleated cells (P less than 0.05) but less than twofold.
      However, MN frequencies in binucleated cells were not equivalent to the
      frequencies of mononucleated cells, since MN in binucleated cells represent two
      nuclei. These results suggest that further study is required to consider CB
      method as a more reliable approach for scoring MN.

PMID- 1975132
TI  - Lack of modifying effects of p-phenylenediamine on induction of gamma-glutamyl
      transpeptidase-positive foci in a medium-term bioassay system using F344 rats.
AB  - The modifying effects of p-phenylenediamine (p-PD) on liver carcinogenesis were
      investigated in male F344/DuCrj rats initially treated with N-nitrosodiethylamine
      (DEN). Two weeks after a single dose of DEN (200 mg/kg, intraperitoneally), rats
      were given p-PD at dietary levels of 1000, 330 and 110 parts per million (ppm),
      or 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) at 600 ppm as a positive
      control for 6 weeks. At week 3 following DEN administration, all animals were
      subjected to partial hepatectomy. Slight retardation of body weight was observed
      in rats treated with p-PD at all dietary levels. Significant increases in
      relative liver weight were found in animals treated with 1000 ppm p-PD.
      Remarkable growth retardation and increased liver weight were found in rats given
      3'-Me-DAB. p-PD did not significantly increase the level of gamma-glutamyl
      transpeptidase (gamma-GT) positive foci observed after DEN initiation. In
      contrast, 3'-Me-DAB demonstrated marked enhancing activity as evidenced by
      significantly increased values for gamma-GT positive foci as compared with the
      controls given DEN alone. The results demonstrate that p-PD does not modify liver
      carcinogenesis in our in vivo medium-term bioassay system.

PMID- 1975133
TI  - In vivo effects of di-n-butyltin dichloride on some enzymes and lipids of rat
      liver plasma membrane.
AB  - The in vivo effects of di-n-butyltin dichloride (DBT) on the enzyme activity and
      lipid constituents of liver plasma membrane were studied in male Albino rats. The
      rats were intraperitoneally administered with 0.1 ml (10% v/v) ethanol either
      alone or containing DBT (10 or 30 mg/kg/d) for 7 consecutive days. A significant
      inhibition of plasma membrane marker enzymes such as 5'-nucleotidase, gamma
      glutamyltranspeptidase, alkaline phosphatase, Mg2(+)-ATPase, Na+/K(+)-ATPase and
      Ca2(+)-ATPase occurred in DBT-treated rats when compared with respective
      controls. Other important bioconstituents such as sialic acid and total
      phospholipid/cholesterol ratio were also significantly decreased in DBT-treated
      rats when compared with corresponding controls. These results suggest that
      interaction of DBT with liver plasma membrane constituents might cause
      derangement of its structural and functional organization, thus leading to
      hepatotoxicity.

PMID- 1975135
TI  - [Recommendations for the soldering of dentures made from stainless steel].

PMID- 1975134
TI  - Mild renal failure induced by subchronic exposure to molybdenum: urinary
      kallikrein excretion as a marker of distal tubular effect.
AB  - In this study we investigated the effect of two molybdenum (Mo) doses (40 and 80
      mg/kg/d) on renal function. Neither dose of Mo was able to induce significant
      hypertension in treated animals. Subchronic exposure to high doses of Mo resulted
      in a delay in body weight gain associated with mild renal failure marked by a
      decrease in glomerular filtration. An increase in diuresis and urinary kallikrein
      excretion associated with unchanged glycosuria and proximal tubular enzymuria
      (alanine aminopeptidase and gamma-glutamyl transpeptidase) evoked a preferential
      mild effect at the distal tubule.

PMID- 1975137
TI  - Homeogene expression patterns and chromosomal imprinting.
AB  - In both mouse and Drosophila, Antennapedia-like homeobox-containing genes
      (homeogenes) display a strict correspondence between the order of genes (3' to
      5') along the chromosome and the order of their expression domains (anterior to
      posterior) in the developing embryo. We show here how this, and other points of
      similarity, may indicate that both species use a common mechanism of chromosomal
      imprinting in order to retain cellular memory of homeogene expression patterns
      throughout embryonic development.

PMID- 1975136
TI  - Reversal of drug-resistant falciparum malaria by calcium antagonists: potential
      for host cell toxicity.
AB  - Agents capable of reversing multidrug resistance (mdr) in falciparum malaria were
      investigated for potentiation of chloroquine accumulation and toxicity in a cell
      culture system. Verapamil, its analog RO11-2933, and desipramine caused a dose
      dependent increase in the accumulation of chloroquine (CQ) within human and mouse
      hepatocytes but not human lung cells. Only those cells in which drug accumulation
      was enhanced by reversing agents reacted positively for P-glycoprotein (PgP)--the
      putative mediator of the enhanced drug efflux characteristic of mdr. Clinically
      achievable concentrations of verapamil (0.4 microM) and desipramine (1 microM)
      increased CQ accumulation within primary mouse hepatocytes by more than 50%. A
      well-differentiated normal human cell line (Hep-G2) was killed in media
      containing a combination of supraphysiological concentrations of CQ and verapamil
      but survived the same concentrations of either drug alone. Reversing agents may
      block PgP-mediated drug export from normal tissues as well as from MDR cells.
      Iatrogenic toxicity resulting from this accumulation of potentially toxic drugs
      such as CQ within normal cells could complicate the reversal of mdr in vivo.

PMID- 1975138
TI  - Biliary lipid secretion early after liver transplantation.

PMID- 1975139
TI  - The synthetic prostaglandin E1 analogue rioprostil reduces the nephrotoxic
      potential of cyclosporine A.
AB  - Acute CyA nephrotoxicity involves alteration in the proximal tubule and leads to
      glomerular lesions. Administration of a vasodilatator agent such as the
      prostaglandin E1 analogue Rioprostil (Bayer AG, BAY 06893) might prevent
      preglomerular vasoconstriction and hence reduce cyclosporin nephrotoxicity. As an
      increased excretion of urinary enzymes as a consequence of CyA-nephrotoxicity is
      well known we investigated in 40 male Wistar rats the excretion of three urinary
      enzymes: the brush border enzyme gamma-glutamyltransferase (GGT), the leucine
      aminopeptidase (LAP), and the lysosomal enzyme N-acetyl-beta-glucosaminidase
      (NAG). Additionally we determined s-creatinine and CyA plasma level. The kidneys
      were studied histologically at the end of the study. Wistar rats receiving 20 or
      50 mg CyA/kg/d showed a marked deterioration in renal function and an increase of
      all urinary enzymes determined. In the rats receiving 20 mg CyA/kg/d and
      Rioprostil (150 micrograms/d) renal function and the enzymes determined remained
      in the normal range. There was no change in the enzyme excretion and only a minor
      improvement of renal function in rats receiving 50 mg CyA/kg/d and Rioprostil.
      Histological findings showed prevention of CyA nephrotoxicity in the 20 mg/kg/d
      group and diminished renal damage in the 50 mg/kg/d group.

PMID- 1975140
TI  - RFLP-DR beta and serological HLA-DR typing of 200 kidney recipients and 1000
      controls.

PMID- 1975141
TI  - Serological, cellular, and molecular biology HLA typing methods for selection of
      unrelated bone marrow donors.

PMID- 1975142
TI  - Characterization of a new strain of HHV-6 (HHV-6SF) recovered from the saliva of
      an HIV-infected individual.
AB  - An isolate of the human herpesvirus-6 (HHV-6SF) recovered from the saliva of an
      HIV-infected individual differs in its cellular host range and certain genomic
      properties from other HHV-6 strains described. HHV-6SF replicates in adult
      peripheral blood mononuclear cells (PMC) substantially better than in fetal cord
      blood PMC and can be grown only in the MT-4 established T cell line. It
      preferentially infects CD4+ lymphocytes but can replicate in CD8+ cells and
      peripheral blood macrophages. It also infects neuroblastoma cells and cell lines
      derived from the gastrointestinal tract. These latter results suggest that this
      herpesvirus could play a role in disorders affecting these tissues. Finally, the
      restriction enzyme pattern of HHV-6SF differs from that of other HHV-6 strains.
      The identification of this distinct HHV-6 strain could indicate an unusual
      biologic variation among viral isolates thus far not observed with other
      herpesviruses.

PMID- 1975143
TI  - [The ecology of the iridoviruses].

PMID- 1975144
TI  - [Effectiveness of electroconvulsive therapy in the light of current approaches to
      the treatment of febrile conditions in schizophrenia].
AB  - The authors review febrile attacks of schizophrenia and the febrile period of the
      malignant neuroleptic syndrome in schizophrenia. Twenty-five schizophrenia
      patients were observed to establish the effect of the ECT on their status. The
      ECT was found to be highly effective in combination with intensive infusion
      therapy aimed at the correction of homeostasis. It was revealed that the
      prognosis and efficacy of the use of the ECT is determined by the stage of the
      development of febrile condition, the leading syndrome and the gravity of
      somatovegetative disorders. The use of the ECT was ineffective in cases where the
      development of a febrile attack reaches the level of amential dull consciousness.

PMID- 1975145
TI  - [Peridural analgesia in the combined treatment of neurologic syndromes in lumbar
      osteochondrosis].
AB  - The authors relate the results of the treatment of 151 patients with the
      remarkable painful syndrome of long standing associated with lumbar
      osteochondrosis. In 74 patients of the main group, peridural administration of
      the synthetic opiates dipidolor and phentanyl provided effective analgesia in the
      lack of sympathetic denervation, arterial hypotension and tissue deafferentation.
      The selective action of the synthetic morphine-like opiates did not reduce the
      activity of the endogenous antinociceptive structures or destroyed the reflex
      mechanisms of sanogenesis. The economic effect obtained as a result of
      introduction of peridural injections of dipidolor and phentanyl into
      multimodality treatment of the neurological syndromes associated with lumbar
      osteochondrosis has been computed.

PMID- 1975146
TI  - [Treatment of drug-resistant depression by intravenous administration of
      antidepressants].
AB  - The proportion of depressed patients no longer responding adequately to oral
      antidepressive medication combined with psychotherapy now amounts to as much as
      15%. Depressive states failing to lift in response to antidepressants are
      referred to in Europe as "therapy-resistant". Before initiating some further form
      of treatment in a case of therapy resistance the diagnosis as well as the
      antidepressive treatment given hitherto (dosage, activity profile, compliance)
      should be reappraised. Where the diagnosis of "therapy-resistant depression" is
      confirmed, intravenous infusions of antidepressants in combination with
      psychotherapy have been found to offer the best prospects of success. With the
      help of daily infusions of maprotiline (ludiomil) and/or clomipramine (anafranil)
      it proved possible in over 1,000 patients suffering from therapy-resistant
      depression to achieve a remission in 60% and a marked improvement in 20%. At
      various research centres in Europe where intravenous drip infusions were
      administered in relatively low dosages, a more rapid onset of action was observed
      with fewer side effects, as well as higher plasma concentrations (thanks to
      avoidance of the first-pass effect) and no problems with respect to compliance.

PMID- 1975147
TI  - Metabolic effects of pulsatile insulin infusion in the elderly.
AB  - The present study investigated the metabolic effects of pulsatile insulin
      delivery at a pulse rate of 2 + 11 and 2 + 18 min in 7 healthy, elderly subjects
      (71.4 +/- 2.1 years), submitted to 260 min controlled iv glucose infusion via the
      Biostator. The endogenous secretion of pancreatic hormones was inhibited by
      somatostain (3 micrograms/min) and glucagon was replaced (67 ng/min) to basal
      levels. The same total insulin dose was delivered on both occasions. Insulin
      infusion rate was 1.3 and 2.0 mIU. kg-1. min-1 during switching on/off of 2 + 11
      and 2 + 18 min, respectively. Blood glucose levels and glucose infusion rate were
      monitored continuously by the Biostator; [D-3-3H]glucose infusion allowed
      determination of glucose turnover. During the last 60 min of the experiment,
      pulsatile insulin at a pulse rate of 2 + 11 vs 2 + 18 min produced a stronger
      inhibition of endogenous glucose production, whereas glucose disappearance rate
      and glucose metabolic clearance rate were similarly affected. Plasma
      triglycerides, apolipoprotein B, and free fatty acids levels were also more
      suppressed during insulin delivery at pulse rate of 2 + 11 than at 2 + 18 min.

PMID- 1975148
TI  - Thyroid status regulates particulate but not soluble TRH-degrading pyroglutamate
      aminopeptidase activity in the rat liver.
AB  - Rat liver contains two topologically different TRH-degrading pyroglutamate
      aminopeptidases. The particulate pyroglutamate aminopeptidase, unlike the soluble
      one, was highly specific for TRH and shared many physico-chemical properties with
      serum thyroliberinase, which is controlled by thyroid hormones. Both enzymes
      convert pGlu His Pro NH2 into His Pro NH2; the latter may be cyclized to cyclo
      His Pro known to possess several biological activities and specific binding sites
      in liver. The aim of the present study was to determine the effects of thyroid
      status on the particulate and soluble enzymes activity and gain more insight into
      their biological role. The regulatory pathway for the particulate pyroglutamate
      aminopeptidase was found similar to that of serum thyroliberinase: their specific
      activities decrease in hypothyroid rats and increase in hyperthyroid rats,
      whereas that of soluble enzyme remains unchanged. We postulate that the
      particulate pyroglutamate aminopeptidase may be a determining factor in the
      concentrations of TRH and/or cyclo His Pro reaching liver cells and a possible
      source for serum thyroliberinase. Taken together, these data suggest that this
      "converting enzyme" acts as a physiological regulator.

PMID- 1975149
TI  - Thyroid growth promoting serum-IgG in endemic goiter.
AB  - In this study a strain of differentiated rat thyroid cells in continuous culture
      was used to detect the presence of thyroid growth promoting immunoglobulins (TGI)
      in IgG preparations of serum of patients with endemic and sporadic euthyroid
      goiters. TGI was detected when FRTL5 cells were used in a mitotic arrest assay by
      costimulating the cells with IgG and a suboptimal dose of TSH. TGI was present in
      65 of 71 endemic goter cases and in 9 of 14 sporadic goiter cases.

PMID- 1975150
TI  - The influence of pancuronium and vecuronium combined with balanced anaesthesia on
      haemodynamics and myocardial oxygen balance.
AB  - The effects of the non-depolarizing muscle relaxants pancuronium (Pancuronium)
      and vecuronium (Norcuron) (0.1 mg/kg) on myocardial blood flow, myocardial oxygen
      consumption, myocardial lactate balance, cardiovascular dynamics and
      electrocardiogram were studied in two groups of eight patients undergoing
      coronary artery bypass surgery. After induction of anaesthesia with 0.015-0.02
      mg/kg flunitrazepam, isoflurane (0.5 vol%) and N2O/O2 (l/l), neuromuscular
      blockade was induced with pancuronium or vecuronium (0.1 mg/kg) combined with a
      single dose of 0.005 mg/kg fentanyl. Haemodynamic measurements were performed and
      the electrocardiogram was recorded before anaesthesia, in steady-state
      anaesthesia, after relaxation with pancuronium or vecuronium combined with
      fentanyl, and after intubation. The haemodynamic data consisted of heart rate,
      cardiac index, stroke volume index, mean arterial pressure, total peripheral
      resistance, pulmonary arterial pressure, pulmonary capillary wedge pressure,
      right atrial pressure, myocardial blood flow, coronary vascular resistance,
      myocardial oxygen consumption, coronary aterio-mixed venous content difference,
      myocardial lactate extraction and rate pressure product. In the vecuronium group,
      heart rate decreased significantly more (21%) than in the pancuronium group (9%).
      Therefore myocardial oxygen consumption (48% resp. 35%) and coronary blood flow
      (31% resp. 18%) decreased more in the vecuronium than in the pancuronium group.
      The higher metabolic demand in the pancuronium group induced a significantly
      lower coronary vascular resistance, because the decrease in coronary perfusion
      pressure was similar in both groups. None of the other haemodynamic parameters
      differed significantly in either patient group. We did not observe ST-segment
      depressions or elevations in the ECG, increases in PCWP or myocardial lactate
      production. Therefore extended myocardial ischaemia can be excluded in our
      patients who received pancuronium or vecuronium for neuromuscular blockade.

PMID- 1975151
TI  - Inhomogeneity of the putaminal lesion in striatonigral degeneration.
AB  - An immunohistochemical topographic study was carried out in the putamen from
      three patients with striatonigral degeneration (SND) using antibody to
      calcineurin (CaN), a neurochemical marker for the striatal medium-size spinous
      neurons. In patients with SND, there was significant depletion of CaN
      immunoreactivity in the putamen with the caudal and lateral portion of the
      putamen being consistently and severely affected. In addition, the SND patients
      showed an inhomogeneous distribution pattern of residual CaN staining in the
      putamen, where remaining CaN immunoreactivity appeared as a characteristic
      patchwork of "islands" resembling the "striosomes" observed by the tyrosine
      hydroxylase or Met-enkephalin immunostaining in the putamen from normal
      individuals. This finding may account for the fact that there are subregional and
      compartmental differences in susceptibility of the medium-sized spinous neurons
      in the putamen with SND.

PMID- 1975152
TI  - Influence of beta-adrenergic blockade upon hemodynamic response to exercise
      assessed by Doppler echocardiography.
AB  - Peak aortic blood flow acceleration and velocity measured by Doppler
      echocardiography have been documented to be accurate descriptors of left
      ventricular systolic function. Both acceleration and velocity are reduced in the
      presence of beta-blockade at rest and during exercise. Whether and to what extent
      the simultaneous alterations in heart rate (HR) due to beta-blockade affect these
      parameters has received little study. In order to determine the influence of
      alterations in HR on Doppler measurements of velocity and acceleration, 10
      healthy men were studied during upright exercise under control conditions,
      following propranolol administration, and following propranolol plus
      transesophageal atrial pacing. In addition, we assessed the response of stroke
      volume (measured as flow velocity integral) during beta-blocked and control
      exercise. Propranolol significantly reduced acceleration and velocity during all
      stages of exercise compared with control values (p less than 0.05). Increasing
      the HR during exercise via pacing had no effect on acceleration or velocity
      compared with propranolol administration alone, thus demonstrating that during
      upright exercise, changes in acceleration and velocity are independent of
      alterations in HR. At low levels of exercise, propranolol significantly reduced
      flow velocity integral (FVI) compared with control (-1.14 cm, p less than 0.05.).
      At high levels of exertion, however, FVI exceeded values obtained during control
      conditions (1.2 cm at stage 4). Pacing during beta-blockade reduced FVI at high
      levels of exercise but had no effect at lower levels. Our results suggest that
      during low levels of exercise stroke volume is increased as a consequence of both
      increased contractility and augmented left ventricular filling.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1975153
TI  - Systemic and regional hemodynamic effects of alpha-adrenoceptor blockade in
      chronic left ventricular dysfunction in the conscious dog.
AB  - In seven dogs with long-standing left ventricular dysfunction induced 16 weeks
      earlier by repetitive transmyocardial direct current (DC) shock, the acute
      hemodynamic effect of the alpha 1-adrenoceptor antagonist urapidil was studied.
      Left ventricular end-diastolic pressure (LVEDP) was significantly increased from
      preshock levels at the time of study and cardiac output was reduced. Plasma
      norepinephrine was significantly increased from control levels and was not
      altered by urapidil infusion. The mean arterial pressure fell in response to
      alpha 1-blockade from 111 to 85 mm Hg, the LVEDP fell from 16 to 9 mm Hg, and
      cardiac output increased from 2.90 to 3.70 L/min (all p less than 0.01). Regional
      blood flows measured by microsphere injection revealed an increase in blood flow
      to skeletal muscle, which had not been significantly decreased by the left
      ventricular dysfunction in this model, and further decreases in splanchnic flow,
      which was already depressed compared with that in normal dogs. Therefore acute
      alpha-adrenoceptor blockade improves central hemodynamics in experimental heart
      failure but does not normalize the resting blood flow maldistribution in this
      model.

PMID- 1975154
TI  - Circadian rhythms in cardiovascular disease.
AB  - Circadian rhythms have long been recognized to occur in many biologic phenomena,
      including secretion of hormones and activities of the autonomic nervous system.
      More recently, circadian rhythms have also been noted to occur in the incidences
      of certain cardiac and cerebrovascular events, including transient myocardial
      ischemia, myocardial infarction, sudden cardiac death, and stroke. The
      pathophysiology and the mechanisms underlying these variations are the focus of
      much investigation. The effects of different drug treatments on these circadian
      rhythms are also being studied. This information should enable better treatment
      strategies to be planned for patients who have either silent or symptomatic
      episodes of transient myocardial ischemia and potentially to prevent the
      occurrence of sudden, catastrophic cardiac events.

PMID- 1975155
TI  - Pharmacologic management of ischemic heart disease with beta-blockers and calcium
      channel blockers.
AB  - In myocardial ischemia beta-blockers reduce myocardial oxygen demand, improve
      flow toward ischemic regions, and have mild antiplatelet and antiarrhythmic
      effects. These agents are effective in chronic stable angina and unstable angina.
      In chronic myocardial ischemia, the beta-blockers timolol, metoprolol, atenolol,
      and propranolol have cardioprotective effects, reducing overall mortality and the
      incidence of recurrent myocardial infarction. Calcium channel blockers, which
      reduce myocardial oxygen demand and improve oxygen supply, are effective in the
      treatment of chronic stable angina, vasospastic angina, and unstable angina.
      Although calcium channel blockers generally have no effect or adverse effects
      when used as primary therapy for acute myocardial infarction, diltiazem (when
      used concomitantly with nitrates or beta-blockers) has been shown to reduce the
      incidence of reinfarction in patients after non-Q wave myocardial infarction.

PMID- 1975156
TI  - Potential gastrointestinal uses of somatostain and its synthetic analogue
      octreotide.
AB  - Octreotide is a long-acting analogue of somatostatin which has been FDA approved
      for symptomatic carcinoid syndrome and for vasoactive intestinal peptide
      producing tumors. Somatostatin and octreotide have significant effects on
      gastrointestinal physiology which may be beneficial for a variety of disorders.
      This paper will review the currently available literature on the use of
      somatostatin and octreotide in non-neoplastic disorders of the gastrointestinal
      tract.

PMID- 1975157
TI  - Continuous acidity monitoring in the study of gastric antisecretory drugs: pH or
      antilog transformation of pH, mean or median?
AB  - The expression of gastric acidity as pH or antilog transformation of pH and the
      use of the mean or the median as the better summary variable are among the major
      problems concerning the assessment of antisecretory drugs' effects by means of
      continuous intraluminal pH monitoring. In this study, we reviewed data deriving
      from 23 normal subjects, 69 asymptomatic duodenal ulcer patients treated with
      bedtime (52) or twice daily (17) doses of H2-antagonists, and 10 H2-receptor
      blocker nonresponders. The whole group underwent continuous 24-h acidity
      monitoring, and the arithmetic mean and median were calculated on each individual
      pH and pH antilog transformed profile. One-way analysis of variance and Kruskall
      Wallis test were used for statistical comparison between the four subgroups
      studied. The greatest discrimination between them was obtained when using the
      mean of pHs [p(F) approximately 0, p[KW] = 2.10(-12)), instead of the median of
      pHs (p[F] = 8.10(-8), p[KW] = 7.10(-8)). The antilog transformation of pH did not
      improve the results. It can be concluded that the use of pH to express gastric
      acidity and the choice of the mean to summarize the drug-related profiles
      provides a better characterization of the acidity behavior than would the antilog
      transformation of pHs and the median.

PMID- 1975158
TI  - Taxol: same name for two drug products.

PMID- 1975159
TI  - Preparation of an attenuated dengue 4 (341750 Carib) virus vaccine. I. Pre
      clinical studies.
AB  - Dengue 4 (DEN-4) virus strain 341750 Carib was modified by serial passage in
      primary canine kidney (PCK) cell cultures. By the 15th PCK passage, this virus
      was less infectious for monkeys and resulted in a significantly reduced viremia
      as compared to the parent DEN-4 virus. The 30th PCK passage of DEN-4 341750 Carib
      was non-infectious for monkeys. A vaccine prepared at the 20th PCK passage in DBS
      FRhL-2 cells stimulated the production of both neutralizing and hemagglutination
      inhibition antibodies in monkeys; these animals were also protected against
      challenge with the homologous strain as well as a heterologous strain of DEN-4.
      An ID50 titration in monkeys resulted in a titer of greater than 10(4) plaque
      forming units (PFU) for the vaccine virus and 0.5 PFU for the parent virus.
      Reduced monkey infectivity of this magnitude has been correlated with human
      attenuation in previous dengue vaccine candidates. The DEN-4 strain 341750 Carib
      PCK-20/FRhL-4 vaccine has been characterized and sufficiently tested to be
      considered for safety and immunogenicity trials in humans.

PMID- 1975160
TI  - Opioid action of analgesic nitrous oxide.

PMID- 1975161
TI  - Development of wheat-sensitive enteropathy in Irish Setters: biochemical changes.
AB  - Biochemical changes in the small intestine during development of naturally
      acquired wheat-sensitive enteropathy of Irish Setters were investigated. To
      distinguish primary biochemical abnormalities from secondary effects of
      intestinal damage, progeny of affected dogs reared on a normal wheat-containing
      diet were compared with their own littermates reared on a cereal-free diet and
      with age-matched clinically normal Irish Setters fed the same wheat-containing
      diet. Peroral jejunal biopsy specimens were sequentially obtained between weaning
      and 1 year of age; specific activity and reorientating sucrose density-gradient
      distribution of organelle marker enzymes were determined. Major primary
      biochemical abnormalities were not detected in affected progeny. In affected dogs
      fed wheat, there was a selective, but secondary, loss of the brush border
      alkaline phosphatase and aminopeptidase N activities. This loss was associated
      with the development of partial villus atrophy, but represented a specific effect
      of dietary wheat on the brush border, not merely a nonspecific effect of mucosal
      damage, because other brush border enzymes, including disaccharidases, were not
      similarly affected. Increased soluble activities of lysosomal and peroxisomal
      marker enzymes late in the disease process may represent alterations in these 2
      organelles as a secondary consequence of mucosal damage.

PMID- 1975162
TI  - Inhaled salmeterol and salbutamol in asthmatic patients. An evaluation of asthma
      symptoms and the possible development of tachyphylaxis.
AB  - Salmeterol (SM) is a new beta 2-adrenoceptor agonist for inhaled use that has
      been shown to produce long-lasting bronchodilation in asthmatic patients. In the
      present study, evaluating efficacy and possible development of tachyphylaxis
      after SM, 12 patients with stable asthma were included after the demonstration of
      reversibility in FEV1 of at least 15% to 200 micrograms salbutamol (SB) or 20% to
      500 micrograms SB. At inclusion all patients were receiving treatment with
      inhaled beta 2-agonists, and 11 of the 12 patients were also receiving inhaled
      corticosteroids. The patients were treated for two 2-wk periods with either
      inhaled SM 50 micrograms twice a day or SB 200 micrograms four times a day,
      following a double-blind, double-dummy, randomized design. The treatment periods
      were separated by a washout period of 1 wk. Dose-response curves to inhaled SB
      were obtained the day before and the day after each treatment period. On each of
      these days, basal FEV1, tremor, heart rate, and blood pressure were recorded and
      were then followed after the inhalation of 100 + 300 + 900 micrograms SB to
      obtain a cumulative dose-response curve. During the treatment periods, as well as
      during the washout week after each treatment, the patients recorded their morning
      and evening peak expiratory flow (PEF) each day before the inhalation of the
      study drug. Subjective asthma symptoms were monitored by a visual analog scale
      after each treatment period. The dose-response curves to SB revealed no signs of
      a reduced response to SB after any of the treatments, but significant increases
      in basal FEV1 and FVC were seen after the SM period (p less than 0.05).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1975164
TI  - Thermal ecology of Naegleria fowleri from a power plant cooling reservoir.
AB  - The pathogenic, free-living amoeba Naegleria fowleri is the causative agent of
      human primary amebic meningoencephalitis. N. fowleri has been isolated from
      thermally elevated aquatic environments worldwide, but temperature factors
      associated with occurrence of the amoeba remain undefined. In this study, a newly
      created cooling reservoir (Clinton Lake, Illinois) was surveyed for Naegleria
      spp. before and after thermal additions from a nuclear power plant. Water and
      sediment samples were collected from heated and unheated arms of the reservoir
      and analyzed for the presence of thermophilic Naegleria spp. and pathogenic N.
      fowleri. Amoebae were identified by morphology, in vitro cultivation, temperature
      tolerance, mouse pathogenicity assay, and DNA restriction fragment length
      analysis. N. fowleri was isolated from the thermally elevated arm but not from
      the ambient-temperature arm of the reservoir. The probability of isolating
      thermophilic Naegleria and pathogenic N. fowleri increased significantly with
      temperature. Repetitive DNA restriction fragment profiles of the N. fowleri
      Clinton Lake isolates and a known N. fowleri strain of human origin were
      homogeneous.

PMID- 1975163
TI  - Transport and deamination of amino acids by a gram-positive, monensin-sensitive
      ruminal bacterium.
AB  - Strain F, a recently isolated ruminal bacterium, grew rapidly with glutamate or
      glutamine as an energy source in the presence but not the absence of Na.
      Monensin, a Na+/H+ antiporter, completely inhibited bacterial growth and
      significantly reduced ammonia production (85%), but 3,3',4',5
      tetrachlorosalicylanide (a protonophore) and valinomycin had little effect on
      growth or ammonia production. Dicyclohexylcarbodiimide, a H(+)-ATPase, inhibitor
      had no effect. The kinetics of glutamate and glutamine transport were biphasic,
      showing unusually high rates at high substrate concentrations. On the basis of
      low substrate concentrations (less than 100 microM), the Km values for glutamate
      and glutamine were 4 and 11 microM, respectively. Strain F had separate carriers
      for glutamate and glutamine which could be driven by a chemical gradient of Na.
      An artificial delta psi was unable to drive transport even when Na was present.
      The glutamate carrier had a single binding site for Na with a Km of 21 mM; the
      glutamine carrier appeared to have more than one binding site, and the Km was 2.8
      mM. Neither carrier could use Li instead of Na. Histidine and serine were also
      rapidly transported by Na-dependent systems, but serine alone did not allow
      growth even when Na was present. Because exponentially growing cells at pH 6.9
      had little delta psi (-3 mV) and a slightly reversed Z delta pH (+17 mV), it
      appeared that the membrane bioenergetics of strain F were solely dependent on Na
      circulation.

PMID- 1975165
TI  - Prognostic value of phenotyping by Ber-H2, Leu-M1, EMA in Hodgkin's disease.
AB  - The purpose of this report is to assess whether phenotyping by three monoclonal
      antibodies routinely used in paraffin sections (Ber-H2-Leu-M1-EMA) and shown to
      be the most useful for diagnosis may be a predictive factor for recurrences.
      Among 563 patients diagnosed as having Hodgkin's disease (24% of whom had
      recurrence), we selected 153 patients with and without recurrence, with matching
      clinical stage. For all of these cases, histologic material was tested by
      immunostainings with satisfactory control samples. No phenotype was specific for
      Hodgkin's disease, although the phenotype Ber-H2-Leu-M1-EMA was predominant. No
      phenotype was found to be a predictive factor for recurrences, and none was
      unchanged during the clinical course, except when recurrence occurred as non
      Hodgkin's lymphoma.

PMID- 1975166
TI  - The clinical use of somatostatin analogues in the treatment of cancer.
AB  - Somatostatin is a regulatory hormone or tissue factor which plays an inhibitory
      role in the normal regulation of several organ systems, including the central
      nervous system, hypothalamus and pituitary gland, the gastrointestinal tract and
      the exocrine and endocrine pancreas. Sandostatin is an analogue of somatostatin
      which has characteristics which makes it a better compound for clinical use than
      native somatostatin: it inhibits GH preferentially over insulin. It has a long
      half-life in the circulation, causing a prolonged inhibitory effect in
      somatostatin-responsive target organs. It is active after subcutaneous
      administration and rebound hypersecretion does not occur. Sandostatin is very
      well tolerated by most patients. Somatostatin receptors remain present on a
      variety of tumours which arise in tissues that contain these receptors normally.
      High numbers of somatostatin receptors have been found on GH-secreting pituitary
      tumours and on most metastatic endocrine pancreatic tumours and carcinoids.
      Sandostatin treatment ameliorates clinical symptoms in most acromegalic patients
      while GH hypersecretion and elevated concentrations of circulating IGF-I are well
      controlled. In most patients hormonal hypersecretion from endocrine pancreatic
      tumours and carcinoids is also suppressed during Sandostatin therapy. This
      results in an instant improvement in the quality of life. There is preliminary
      evidence of control of tumour growth. The presence of high numbers of
      somatostatin receptors on tumours enables in vivo receptor-imaging, with
      123iodine coupled to a somatostatin analogue. This newly developed technique
      provides for the first time the possibility of localization of the primary
      tumours and their metastases and a prediction of which patients may respond to
      treatment with Sandostatin. Theoretically this somatostatin-receptor imaging
      technique represents a new approach which may be extended to other receptor
      containing tumours. Therefore it may provide a new, powerful alternative to
      tumour localization performed with monoclonal antibody technology. Another
      potential development is the use of beta-emitting isotopes coupled to
      somatostatin analogues for therapeutic irradiation. Somatostatin analogues exert
      potent inhibitory effects on the growth of a variety of experimental tumour
      models in animals. Several mechanisms of action have been proposed including the
      direct antiproliferative effects of somatostatin and its analogues in a variety
      of tumour cell cultures. Most well-differentiated human brain tumours like
      meningiomas and low-grade astrocytomas contain somatostatin receptors, while
      undifferentiated brain tumours mainly contain EGF receptors. Fifteen percent of
      human breast carcinomas contain somatostatin receptors; those which do have a
      better prognosis. It can be concluded that somatostatin is an endogenous,
      naturally occurring inhibitory growth factor.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1975167
TI  - New endocrine approaches to breast cancer.

PMID- 1975169
TI  - Receptor-mediated generation of an EDRF-like intermediate in a neuronal cell line
      detected by spin trapping techniques.
AB  - We have studied receptor-mediated generation of an activator of soluble guanylate
      cyclase in cultured mouse neuroblastoma cells (clone N1E-115) by ESR/spin
      trapping spectroscopy. A spin adduct was detected during the activation of
      muscarinic receptors by carbamylcholine in the presence of the spin trap 3,5
      dibromo 4-nitrosobenzene sulphonate (DBNBS). The spin adduct does not correspond
      to that originating from the free radical nitric oxide or hydroxylamine. The same
      adduct was generated in cytosol preparations from N1E-115 cells incubated with L
      arginine, NADPH, in the presence of calcium. The use of isotopically labelled
      guanidino-N15-L-arginine supported the generation of a DBNBS spin trapped adduct
      originating from the guanidino moiety of L-arginine. Superoxide dismutase (SOD)
      stabilized the precursor of the spin adduct as well as the activator of soluble
      guanylate cyclase derived from L-arginine. Our results provide direct evidence
      for the receptor-mediated formation of a diffusible precursor of NO. derived from
      L-arginine.

PMID- 1975168
TI  - Role of cysteine and taurine in regulating glutathione synthesis by periportal
      and perivenous hepatocytes.
AB  - The uptake and metabolism of 35S-labelled sulphur amino acids were compared in
      periportal (PP) and perivenous (PV) rat hepatocytes, isolated by
      digitonin/collagenase perfusion, to identify the factors underlying the
      previously observed [Kera, Penttila & Lindros, Biochem. J. (1988) 254, 411-417]
      higher rate of GSH replenishment in PP cells. The buthionine sulphoximine
      inhibitable synthesis of GSH was faster in PP than in PV hepatocytes with both
      cysteine (6.1 versus 5.0 mumol/h per g of cells) and methionine (4.5 versus 3.3
      mumol/h per g) as well as with endogenous precursors and L-2-oxo-4
      thiazolidinecarboxylate as substrates. However, the uptake of cysteine by PP
      cells was slower than by PV cells (8.6 versus 10.3 mumol/h per g of cells),
      whereas methionine was taken up at similar rates. The activity of gamma
      glutamylcysteine synthetase (GCS) was slightly higher in digitonin lysates from
      the PP than from the PV zone. Production of sulphate, the major catabolite of
      [35S]cysteine sulphur, as well as incorporation of the label into protein
      occurred at similar rates in PP and PV cells. Taurine, on the other hand, was
      produced from [35S]cysteine much faster by PV than by PP cells (0.7 versus 0.1
      mumol/h per g of cells). Accordingly, the taurine content of PV hepatocytes
      tended to be higher and to increase faster during incubation with methionine.
      These results imply that metabolism of taurine is highly zonated within the
      acinus. They also suggest that both the slightly lower GCS activity and the fast
      metabolism of cysteine to taurine limit the capacity of PV hepatocytes to
      synthesize GSH.

PMID- 1975170
TI  - Prosomatostatin II processing is initiated in the trans-Golgi network of
      anglerfish pancreatic cells.
AB  - Anglerfish prosomatostatin II, the precursor of somatostatin-28 II, is produced
      in different cells from prosomatostatin I, by a cleavage at Arg73. Antibodies
      were raised against the carboxy-terminal [64-72] portion of the precursor II
      upstream from somatostatin-28 II sequence. These antibodies recognized only this
      epitope when unmasked from the entire precursor, allowing the detection of the [1
      72] domain which was isolated from pancreatic islets extracts. The antibodies
      were used to monitor the peptide bond cleavage occurring at the carboxy terminus
      of Arg73 to generate somatostatin-28 II. Immunocytochemistry revealed labeling
      both in the vesicles budding from the trans-Golgi network and in the dense core
      granules. Together, these data support the conclusions that i) prohormone
      processing is initiated in the Golgi apparatus of the pancreatic islet cells; ii)
      the "non-hormonal" [1-72] amino-terminal domain of the precursor may be involved
      in some intra and/or extra-cellular function(s).

PMID- 1975171
TI  - Characterization of beta-adrenoceptors on rat skeletal muscle cells grown in
      vitro.
AB  - The binding properties of an hydrophilic beta-adrenergic receptor radioligand, (
      )[3H](4-(3-tert-butylamino-2-hydroxypropoxy)-benzimidazolo-2-one ); ([3H]CGP
      12177), were investigated in rat skeletal muscle cells in culture. The binding of
      [3H]CGP-12177 at 25 degrees was saturable, reversible and of high affinity (Kd =
      1.3 +/- 0.3 nM). The maximal number of [3H]CGP-12177 binding sites was 30.6 +/-
      3.2 fmol/dish (34 +/- 3.5 fmol/mg protein). beta-Adrenergic agonists and
      antagonists inhibited [3H]CGP-12177 binding. The competing ligand inhibition
      binding is a typical one for beta 2-adrenoceptors. The increase in beta
      adrenoceptors was independent of cell fusion. Amiodarone (10(-5) M) decreased the
      beta-adrenoceptor number in skeletal muscle cells differentiated in vitro by 48%,
      while the affinity for [3H]CGP-12177 was not affected.

PMID- 1975172
TI  - Glutathione-degrading capacities of liver and kidney in different species.
AB  - Although the liver is recognized as a major site of glutathione (GSH) synthesis,
      it is thought to play only a minor role in GSH catabolism. This is primarily
      because in the rat, the most commonly used experimental animal, hepatic gamma
      glutamyltransferase (gamma-GT) activity is very low, whereas kidney activity is
      quite high. gamma-GT is the only enzyme known to catalyze the initial step in GSH
      degradation. The present work compares gamma-GT and dipeptidase activities in
      liver, kidney, and gallbladder of six mammalian species to assess the importance
      of hepatobiliary catabolism of GSH, relative to renal degradation. Marked species
      differences were observed in gamma-GT activities, and in kidney to liver (K/L)
      ratios for both gamma-GT concentration (milliunits/mg protein) and whole organ
      activities (total activity per liver or two kidneys). The K/L concentration
      ratios for gamma-GT activities ranged from 875 in the rat to 15 in the guinea
      pig. Whole organ gamma-GT ratios were approximately 150 in mouse and rat, and
      only 2-5 in guinea pig. pig, and macaque. Human K/L ratios calculated from gamma
      GT activities reported previously were similar to those of the guinea pig.
      Species differences were also observed in K/L ratios for dipeptidase activities,
      though these differences were not as large as those for gamma-GT, gamma-GT and
      dipeptidase activities were also measured in gallbladders of all species examined
      (except rat which does not have this organ), and were found to be comparable to
      those of liver. These results suggest that in species such as the guinea pig and
      perhaps humans, the liver and biliary tree play a prominent role in GSH turnover.
      Because of the low hepatic and high renal gamma-GT activities of the rat, and
      because it does not have a gallbladder, this species may not be the best model
      for studying the catabolism of GSH and GSH conjugates. Use of the rat model may
      underestimate the contribution of liver, and overestimate that of kidney, in
      these degradative processes.

PMID- 1975173
TI  - Illustrated histopathologic classification criteria for selected vasculitis
      syndromes. American College of Rheumatology Subcommittee on Classification of
      Vasculitis.
AB  - We describe the histopathologic criteria for the diagnosis of 7 selected
      vasculitis syndromes: polyarteritis nodosa, Churg-Strauss syndrome, Wegener's
      granulomatosis, hypersensitivity vasculitis, Henoch-Schonlein purpura, giant cell
      (temporal) arteritis, and Takayasu arteritis. The criteria apply to the
      stereotypical cases in each category; they were formulated after a review of
      submitted biopsy material from 278 of the 1,000 patients entered into the
      American College of Rheumatology Vasculitis Study Registry, and from prior
      experience with the pathologic diagnosis of vasculitis in 1,079 nonregistry
      patients.

PMID- 1975174
TI  - The American College of Rheumatology 1990 criteria for the classification of
      polyarteritis nodosa.
AB  - Criteria for the classification of polyarteritis nodosa were developed by
      comparing 118 patients who had this disease with 689 control patients who had
      other forms of vasculitis. For the traditional format classification, 10 criteria
      were selected: weight loss greater than or equal to 4 kg, livedo reticularis,
      testicular pain or tenderness, myalgias, mononeuropathy or polyneuropathy,
      diastolic blood pressure greater than 90 mm Hg, elevated blood urea nitrogen or
      serum creatinine levels, presence of hepatitis B reactants in serum,
      arteriographic abnormality, and presence of granulocyte or mixed leukocyte
      infiltrate in an arterial wall on biopsy. The presence of 3 or more of these 10
      criteria was associated with a sensitivity of 82.2% and specificity of 86.6%. A
      classification tree was also constructed, with 6 criteria being selected. Three
      of these, angiographic abnormality, biopsy-proven granulocyte or mixed leukocyte
      infiltrate in arterial wall, and neuropathy, were criteria used in the
      traditional format. The other 3 criteria used in the tree format included the
      patient's sex, weight loss greater than 6.5 kg, and elevated serum aspartate
      aminotransferase or alanine aminotransferase levels above the range of normal.
      The classification tree yielded a sensitivity of 87.3% and a specificity of
      89.3%.

PMID- 1975175
TI  - The American College of Rheumatology 1990 criteria for the classification of
      Takayasu arteritis.
AB  - Criteria for the classification of Takayasu arteritis were developed by comparing
      63 patients who had this disease with 744 control patients with other forms of
      vasculitis. Six criteria were selected for the traditional format classification:
      onset at age less than or equal to 40 years, claudication of an extremity,
      decreased brachial artery pulse, greater than 10 mm Hg difference in systolic
      blood pressure between arms, a bruit over the subclavian arteries or the aorta,
      and arteriographic evidence of narrowing or occlusion of the entire aorta, its
      primary branches, or large arteries in the proximal upper or lower extremities.
      The presence of 3 or more of these 6 criteria demonstrated a sensitivity of 90.5%
      and a specificity of 97.8%. A classification tree also was constructed with 5 of
      these 6 criteria, omitting claudication of an extremity. The classification tree
      demonstrated a sensitivity of 92.1% and a specificity of 97.0%.

PMID- 1975176
TI  - CD8+ lymphocytes from patients with systemic lupus erythematosus sustain, rather
      than suppress, spontaneous polyclonal IgG production and synergize with CD4+
      cells to support autoantibody synthesis.
AB  - The cellular requirements for B cell hyperactivity in systemic lupus
      erythematosus (SLE) were studied. Removal of either CD8+ or CD4+ lymphocyte
      markedly decreased the spontaneous in vitro production of polyclonal IgG and of
      antigen-specific (anti-double-stranded DNA and antinucleoprotein) antibodies by
      SLE peripheral blood mononuclear cells (PBMC). The CD8+ lymphocytes that
      sustained IgG production were CD3+, HLA-DR+, and their activity was abrogated by
      preincubation with anti-HLA-DR monoclonal antibody. When both CD4+ and CD8+ cells
      were removed, the readdition of either subset partially restored polyclonal IgG
      production, but both cell subsets were required to reconstitute autoantibody
      production. Purified SLE B cell cultures, which generated only 15% of the IgG
      produced by unseparated PBMC, were fully reconstituted only by mixtures of CD4+
      with CD8+ cells, and with CD8-, CD4-, CD16+ cells. At least part of the support
      for spontaneous IgG production can be attributed to endogenous interleukin-2 and
      interleukin-6.

PMID- 1975177
TI  - HLA-D region genes associated with autoantibody responses to histidyl-transfer
      RNA synthetase (Jo-1) and other translation-related factors in myositis.
AB  - Myositis has been associated with HLA-B8 and DR3, especially in white patients
      with polymyositis and serum anti-Jo-1 antibodies. Twenty-eight patients with
      myositis and serum translation-related autoantibodies anti-Jo-1, anti-PL-7, anti
      PL-12, anti-KJ, and anti-SRP were studied for HLA class II specificities by
      Southern blotting with HLA-DR beta, DQ beta, and DQ alpha probes. The association
      of HLA-DR3 (DRw17) with anti-Jo-1 antibodies in white myositis patients was
      confirmed (P = 0.003, relative risk 8.9). However, HLA-DRw52 haplotypes,
      regardless of subtype, were present in all of the white and black patients with
      serum anti-Jo-1 and other translation-related autoantibodies. Moreover, one anti
      Jo-1 positive patient had HLA-DRw8, an HLA-DRw52 haplotype on which the DR beta 3
      gene has been partially deleted. No HLA-DQ specificity or allele was common to
      all patients. The HLA-DR3, DR5, DRw6, and DRw8 haplotypes, which bear the HLA
      DRw52 specificity, share the most homology in the DR beta 1 first hypervariable
      region at amino acid positions 9-13. Thus, this DR beta 1 region appears to be
      the most likely candidate "epitope" for translation-related autoimmune responses
      in inflammatory myositis.

PMID- 1975178
TI  - Genetic variation in the cholesteryl ester transfer protein and apolipoprotein A
      I genes and its relation to coronary heart disease in a Sri Lankan population.
AB  - The influence of variation in the genes for cholesteryl ester transfer protein
      and apolipoprotein A-I was investigated in 95 patients with coronary heart
      disease and 95 matched control subjects of South East Asian extraction.
      Restriction fragment length polymorphisms (RFLPs) linked to the cholesteryl ester
      transfer protein gene TaqIA and TaqIB, and to the apolipoprotein A-I gene SstI,
      were examined to investigate the extent of genetic variation at these loci. None
      of the alleles defined by these RFLPs were associated with increased coronary
      risk. Analysis of the data by division of high density lipoprotein-cholesterol
      levels into tertiles showed a trend of a higher frequency of B1 allele (presence
      of the TaqIB site) with reduced high density lipoprotein levels. The B1 allele
      was more frequent in control subjects, with low high density lipoprotein levels
      (P less than 0.02), but not in coronary heart disease patients. The differences
      became significant for both groups (P less than 0.05) when the data of non
      smokers were analysed separately.

PMID- 1975179
TI  - Genetic evidence from 7 families that the apolipoprotein B gene is not involved
      in familial combined hyperlipidemia.
AB  - Familial combined hyperlipidemia (FCHL) is the most common genetic form of
      hyperlipidemia in which affected individuals manifest multiple lipoprotein
      phenotypes. Although the molecular defect is still unknown, several kinetic
      studies have demonstrated increased turnover rates of apolipoprotein B (apo B) in
      patients with FCHL, irrespective of their lipoprotein phenotype. Using 3
      restriction fragment length polymorphisms (RFLPs) of the apo B gene (XbaI, MspI
      and EcoRI) we have investigated 33 families which fulfill the diagnostic criteria
      of FCHL. No significant difference in allele frequency was found between 33
      unrelated individuals with FCHL and 107 normolipidemic controls. 3-RFLP
      haplotypes were constructed in each pedigree. A co-segregation analysis was
      performed in 7 informative families. In no family was co-segregation observed
      between the haplotype of the apo B gene and the phenotype of FCHL. These data are
      not compatible with the hypothesis that FCHL is caused by mutations of the apo B
      gene acting as a simple mendelian trait.

PMID- 1975180
TI  - [Dipeptidylpeptidase IV activity in human lymphocytes in hepatobiliary diseases].
AB  - Lymphocytic dipeptidylaminopeptidase IV (DP-IV; E.C.3.4.14.5.) is described as a
      marker enzyme of immunostimulant T-lymphocytes as well as functional
      characteristic of IL-2-producing cells. Mononuclear cells of periphere blood
      (MNC) were isolated by density gradient centrifugation followed by
      enzymcytochemical staining of DP-IV positive cells and measuring of DP-IV enzyme
      activity using chromogenic substrates. As relative sign of single cell DP-IV
      activity we calculated average DP-IV activities of DP-IV positive cells. Blood
      samples from 14 patients with acute virus hepatitis, 30 cases of chronic active
      liver disease, 61 cases with liver cirrhosis of various kind and 19 patients with
      fatty liver and toxic hepatitis were investigated. As standard of comparison we
      used a group of healthy blood donors. By this way significant differences of
      described DP-IV parameters between some groups of liver disease were evident.
      Using an aetiologic classification of investigated liver diseases we found highly
      significant increased single cell activities in hepatitis-B associated cases in
      comparison to remarkable lower lower values in autoimmune cases. Different
      hypothesis about changes of lymphocytic dipeptidylaminopeptidase IV as a part of
      disturbed immunoregulation in chronic liver diseases were discussed.

PMID- 1975181
TI  - The serum activities of AP, gamma-GT, GlDH and GPT after bile duct obstruction
      and ethionine in the rat.
AB  - The increase of activity of the enzymes AP, Gamma-GT, GlDH and GPT was
      investigated in this study with regard to its pathomechanism. The increase of AP
      is known to be caused by a de novo-protein synthesis in the liver, as several
      investigators have demonstrated using protein synthesis inhibitors. In this study
      female Wistar rats were partly sham-operated, partly bile duct-obstructed. One
      half of each group received the protein synthesis inhibitor ethionine, 24 h after
      bile duct obstruction in the group with ethionine the following enzyme activities
      were measured in the serum: AP 216 +/- 80 U/l; gamma-GT 4.5 +/- 1.9 U/l; GlDH 85
      +/- 26 U/l; GPT 375 +/- 163 U/l. In the group without ethionine the activities
      were: AP 459 +/- 69 U/l; gamma-GT 4 +/- 0.9 U/l; GlDH 120 +/- 81 U/l; GPT 417 +/-
      191 U/l. Because the differences between the groups with and without ethionine
      were not significant with the exception of AP, it is concluded that in the early
      phase of bile duct obstruction up to 24 h no influence of de novo-protein
      synthesis can be demonstrated in the elevation of the activities of gamma-GT,
      GlDH and GPT.

PMID- 1975182
TI  - The effects of alpha-methyl-p-tyrosine pretreatment on ethanol-induced narcosis
      and hypothermia, as well as in the development of tolerance to these effects in
      UChA and UChB rats.
AB  - We have previously reported that UChA rats (genetically low ethanol consumer)
      develop tolerance to narcosis time easier than UChB rats (genetically high
      ethanol consumer). We also have reported that UChA rats develop tolerance to the
      hypothermic effect of ethanol, while in UChB rats the repeated administration of
      ethanol induces sensitization towards this effect. In the present paper the
      effects of alpha-methyl-p-tyrosine (AMPT)--a competitive inhibitor of
      norepinephrine synthesis--on ethanol-induced narcosis and hypothermia, as well as
      in the development of tolerance to these effects, were studied in both strains of
      rats. Results obtained show that AMPT pretreatment induced a significantly higher
      increase in narcosis time and hypothermia, as well as, greater susceptibility to
      ethanol toxicity in UChB than UChA rats. Furthermore, the simultaneous treatment
      with AMPT and ethanol did not change the development of tolerance to narcosis
      time in both strains and to hypothermia and sensitization in UChA and UChB rats
      respectively.

PMID- 1975183
TI  - Gamma-glutamyl transferase ectoactivity in the intact rat liver: effect of
      chronic alcohol consumption.
AB  - The localization of gamma-glutamyl transferase (GGT) in the intact rat liver was
      studied by a new approach in which the chromogenic gamma-glutamyl donor substrate
      of GGT gamma-glutamyl-p-nitroanilide is perfused through the portal vein to yield
      p-nitroaniline, which is monitored spectrophotometrically. GGT activity was
      markedly increased by the gamma-glutamyl acceptors glycyl-glycine, cystine and
      methionine, following Michaelis-Menten kinetics. Infusion of glutathione (GSH),
      the natural substrate of GGT, was shown to markedly reduce or to abolish the
      formation of p-nitroaniline without entering the liver cells, indicating the
      existence of a GGT ectoactivity accessible to the sinusoidal circulation. This
      ectoenzyme was shown to remove significant amounts of GSH from the circulation,
      amounting, in the naive rat, to 20-25% of the net rate at which GSH is
      contributed by the liver into the circulation. Chronic alcohol consumption is
      known to increase hepatic GGT activity, although the biological significance of
      such an effect remains unknown. Present studies show that chronic administration
      of alcohol to rats leads to a significant (40-75%) increase in hepatic GGT
      ectoactivity. GGT ectoactivity significantly correlates with total liver GGT,
      both in control and alcohol-treated animals (r = .76 and r = .90, respectively).
      Livers of alcohol-fed rats showed an increased (80-110%) capacity to remove
      circulating GSH which strongly correlated with total liver GGT (r = .96; p less
      than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1975184
TI  - Exclusion of the autosomal dominant retinitis pigmentosa gene from a substantial
      region of chromosome 1: study of a large Australian family.
AB  - In an attempt to map the gene(s) responsible for autosomal dominant retinitis
      pigmentosa (ADRP), the technique of reverse genetics was used on a large
      multigenerational Australian pedigree. The family demonstrated a form of the
      disease which appears to be less severe than that observed in the Irish pedigree.
      It was typed for 10 restriction fragment length polymorphism (RFLP) markers on
      chromosome 1. The data from the linkage study was analysed using the programs
      LIPED 3; six markers gave informative results. The ADRP gene was excluded from
      this family from 102 cM using previously prepared chromosome 1 maps. This
      accounts for 36% of chromosome 1 which is estimated to be the longest human
      chromosome.

PMID- 1975185
TI  - Multiple endocrine neoplasia type IIb.

PMID- 1975186
TI  - Bolus dose esmolol for anesthesia: is there a need?

PMID- 1975187
TI  - A single bolus dose of esmolol in the prevention of intubation-induced
      tachycardia and hypertension in an ambulatory surgery unit.
AB  - The efficacy of a single bolus dose of esmolol in the prevention of intubation
      induced tachycardia and hypertension was studied in a double-blind manner. Thirty
      patients from the Ambulatory Surgery Unit at Rush-Presbyterian-St. Luke's Medical
      Center were prospectively randomized to receive a placebo, 100 mg of esmolol, or
      200 mg of esmolol immediately prior to induction (2.5 to 3.0 minutes before
      intubation). The groups were similar in demographic characteristics and with
      regard to preoperative blood pressure (BP) and heart rate (HR). Anesthetic
      management was standardized for all patients. Esmolol 100 mg (1.4 +/- 0.3 mg/kg)
      and 200 mg (2.6 +/- 0.7 mg/kg) significantly (p less than 0.05) blunted the
      maximum increases in HR and BP following intubation. The average maximum HR
      increase in the placebo group was 40% as opposed to 16% in the esmolol 100 mg
      group and 14% in the esmolol 200 mg group. Both esmolol groups blunted the
      tachycardic response over a 4-minute postintubation time period. The average
      maximum BP increase was 47% in the placebo group versus 22% and 19% in the
      esmolol 100 mg and esmolol 200 mg groups, respectively. There were no significant
      differences between the two esmolol groups. This study demonstrates the efficacy
      of a single bolus dose of esmolol in blunting the tachycardic and hypertensive
      responses to laryngoscopy and intubation in an ambulatory surgery setting.

PMID- 1975188
TI  - Intraoperative use of bolus doses of esmolol to treat tachycardia.
AB  - A randomized, double-blind, parallel, placebo-controlled study was conducted to
      determine the safety and efficacy of intravenous (IV) bolus administration of
      esmolol in treating intraoperative tachycardia in patients undergoing noncardiac
      general surgery. Forty-eight ASA II-IV patients were randomized into three equal
      groups to receive either placebo, esmolol 50 mg, or esmolol 100 mg. Premedication
      (lorazepam) and anesthetic induction techniques (thiopental sodium and
      succinylcholine) were identical between groups. Approximately 20 minutes after
      intubation, during isoflurane/N2O/O2 maintenance anesthesia, patients with
      systolic pressure (SBP) greater than or equal to 110 mmHg were advanced into a 10
      minute study drug period if one of two conditions were met: (1) heart rate (HR)
      was greater than or equal to 95 beats/minute, or (2) an increase in HR of greater
      than 20% above preinduction baseline occurred. After two consecutive recordings
      of HR and blood pressure (BP), the study drug (or placebo) was injected. HR was
      recorded every 30 seconds and BP was recorded every minute during the ensuing 10
      minute period. Compared to placebo responses, HR was significantly reduced with
      both doses of esmolol within 1 minute of bolus injection and remained below
      placebo levels for 5 minutes after 50 mg of esmolol and for 9.5 minutes after 100
      mg of esmolol. There were, however, only minor differences among groups with
      respect to SBP, diastolic blood pressure (DBP), and mean blood pressure (MBP)
      changes. CONCLUSION: Bolus administration of esmolol can produce a rapid
      reduction of HR with relatively few adverse effects in an unhealthy surgical
      population.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1975189
TI  - Attenuation of hemodynamic responses to rapid sequence induction and intubation
      in healthy patients with a single bolus of esmolol.
AB  - The effectiveness of a single preinduction intravenous (IV) bolus of esmolol in
      blunting hemodynamic responses to rapid sequence induction and tracheal
      intubation was evaluated. In a randomized double-blind study, 32 ASA I and II
      healthy patients scheduled for surgery were monitored with electrocardiography
      (EKG) lead V5, arterial cannulation, and impedance cardiography. After
      preoxygenation and a priming dose of vecuronium (0.01 mg/kg), patients received
      either saline (n = 12), esmolol 100 mg (n = 10), or esmolol 200 mg (n = 10) as an
      IV bolus (20 ml volume). This procedure was immediately followed by a 5 ml IV
      saline flush, cricoid pressure, thiopental sodium 5 mg/kg, and succinylcholine
      1.5 mg/kg. Patients receiving 200 mg of esmolol had a 50% reduction in the usual
      tachycardia associated with induction and a greater decline in systolic blood
      pressure (SP) (by 50%) prior to intubation as compared with the placebo group (p
      less than 0.05). The increase in diastolic blood pressure (DP) and the reduction
      in stroke volume (SV) produced by induction and intubation were similar in all
      the groups. Plasma norepinephrine levels at 1.5 minutes after intubation
      increased in the esmolol groups about 130% above that measured in the placebo
      group. This finding was associated with a more gradual return of peripheral
      resistance to baseline following tracheal intubation. However, both doses of
      esmolol effectively attenuated heart rate (HR), SP, and rate pressure product
      (RPP) increases (p less than 0.05 vs placebo) produced by laryngoscopy and
      tracheal intubation.

PMID- 1975190
TI  - Prolonged neuromuscular blockade following vecuronium infusion.
AB  - Administration of vecuronium by infusion is an increasingly common technique,
      both in the operating room and in the intensive care unit (ICU), for patients
      requiring prolonged neuromuscular blockade and mechanical ventilation. The major
      advantage of vecuronium over older neuromuscular blocking agents is its rapid
      excretion and intermediate duration of action. Prior to the current case report,
      the longest reported continuous paralysis after the cessation of a vecuronium
      infusion was 90 hours. A case of an 81-year-old patient with renal failure and
      subclinical chronic cirrhosis of the liver, who remained paralyzed for 13 days
      following a vecuronium infusion, is described. Intensive monitoring of
      neuromuscular function is recommended whenever muscle relaxants are administered
      by continuous infusion.

PMID- 1975191
TI  - Immunohistochemical localization of peptide-containing nerves in human airways:
      age-related changes.
AB  - Bronchial reactivity changes during childhood, indicating possible changes in
      neural control. Nerves supplying the intrapulmonary airways were therefore
      studied in autopsy tissue from 14 normal infants (0 to 3.5 yr), 3 children (8.3
      to 10.75 yr), and 4 adults (17 to 24 yr). An indirect immunofluorescence
      technique was used to study the distribution and relative number of nerve fibers
      containing the general neuronal markers protein gene product 9.5 and
      synaptophysin. Nerve subpopulations were identified using antisera to
      neuropeptide tyrosine, vasoactive intestine polypeptide, somatostatin, substance
      P, calcitonin gene-related peptide, and the enzyme tyrosine hydroxylase. Between
      birth and 3 yr, the distribution and relative number of immunoreactive nerves
      shown by both the general neuronal markers and specific antisera did not change.
      Neuropeptide tyrosine-immunoreactive nerves were the most common peptide
      containing nerve subpopulation identified in the human lung, supplying bronchial
      smooth muscle, submucosal glands, cartilage, and submucosa. Other peptide
      containing nerves exhibited distinct distribution patterns. Two differences in
      the airway innervation were identified between cases aged 0 to 3.5 yr and the
      older age groups. Relatively fewer peptide-containing nerves occurred in the
      adult bronchioli and respiratory unit, but the relative number of vasoactive
      intestinal polypeptide-containing nerves supplying the bronchial and bronchiolar
      smooth muscle was greater in the two older age groups. Given these apparent age
      related differences in the number of peptide-containing nerves supplying the
      human airway, studies on the development of peptide receptors are indicated.

PMID- 1975192
TI  - [Long QT syndrome: new problems in an old subject].

PMID- 1975193
TI  - A proposal for immunotherapy of HIV seropositive healthy individuals using an HIV
      envelope protein devoid of CD4 binding activity.

PMID- 1975194
TI  - Natural killer cell activity of rhesus macaques against retrovirus-pulsed CD4+
      target cells.
AB  - Rhesus peripheral blood mononuclear cells (PBMC) fail to demonstrate natural
      killer (NK) activity against the human T-cell lines CEM, CEM x 174, or SUP-T1.
      However, these cell lines could act as NK-sensitive target cells if they were
      pulsed with heat-inactivated, whole simian immunodeficiency virus (SIV). The
      ability of these SIV-pulsed T-cell lines to act as NK-sensitive target cells was
      directly related to the relative density of CD4 on their surface. Target cell
      generation was inhibited by preincubation of cell lines with CD4 monoclonal
      antibody (MAb) with specificity for the SIV binding site. In addition, NK
      activity was seen against target cells that had been prepared with human
      immunodeficiency virus type 1 (HIV-1) gp120, nonglycosylated gp120, env A of
      feline leukemia virus (FeLV), and simian type D retrovirus (SRV). Addition of
      leupeptin to target cells prior to SIV pulsing did not result in a significant
      decrease in cytotoxic activity, suggesting that processing is not required for
      the generation of target cells. The cells that mediate NK activity are
      nonadherent, do not form rosettes with AET-treated sheep red blood cells (SRBC),
      and are phenotypically CD16+ and CD8+. NK activity of SIV-infected macaques was
      significantly decreased against both K562 cells and SIV-pulsed target cells as
      compared with uninfected animals. However, treatment of PBMC with interleukin-2
      (IL-2) resulted in a partial restoration of NK activity.

PMID- 1975195
TI  - Effect of four heavy metals on the biology of Nostoc muscorum.
AB  - This study presents the effects of Cr, Pb, Ni and Ag on growth, pigments,
      protein, DNA, RNA, heterocyst frequency, uptake of NH4+ and NO3-, loss of
      electrolytes (Na+ and K+), nitrate reductase and glutamine synthetase activities
      of Nostoc muscorum. The statistical tests revealed a direct positive correlation
      between the metal concentration and inhibition of different processes. Ni was
      found to be more toxic against growth, pigments and heterocyst differentiation
      compared to the other metals. Inhibition of pigment showed the following trend:
      chlorophyll greater than phycocyanin greater than carotenoid. No generalized
      trend for inhibition of macromolecules was observed. The loss of K+ and Na+ as
      affected by Cr, Ni and Pb was similar but more pronounced for K+ than Na+. The
      inhibition of physiological variables depicted the following trend: Na+ loss
      greater than K+ loss greater than glutamine synthetase greater than NH4+ uptake
      greater than growth greater than NO3- uptake greater than nitrate reductase
      greater than heterocyst frequency. This study therefore suggests that loss of
      electrolytes can be used as a first signal of metal toxicity in cyanobacteria.
      However, further study is needed to confirm whether the abnormality induced by
      nickel (branch formation) is a physiological or genetic phenomenon.

PMID- 1975196
TI  - A dose-ranging study to evaluate the beta-adrenoceptor selectivity of single
      doses of betaxolol.
AB  - 1. Six normal subjects were given single oral doses of betaxolol 10 mg (B10), 20
      mg (B20), 40 mg (B40), 80 mg (B80), propranolol 40 mg (P40), or placebo (PL) in a
      single-blind randomised cross-over design. 2. beta 1-adrenoceptor blockade was
      assessed by reductions in exercise heart rate. Betaxolol produced dose-related
      reductions in exercise heart rate (beats min-1) up to a ceiling at B40, after
      which B80 showed a lesser effect: (158 +/- 8 PL, 128 +/- 3 B10, 123 +/- 2 B20,
      116 +/- 4 B40, 136 +/- 10 B80, 135 +/- 4 P40). All doses of betaxolol (except
      B80) produced greater reductions compared with P40: (B10 P less than 0.001, B20 P
      less than 0.005, B40 P less than 0.001). 3. beta 2-adrenoceptor blockade was
      assessed by attenuation of finger tremor and cardiovascular responses to graded
      infusions of i.v. isoprenaline. Dose-response curves were constructed and the
      doses required to increase heart rate by 25 beats min-1, finger tremor by 200%,
      calf blood flow by 0.5 ml dl-1 min-1, and decrease diastolic blood pressure by 10
      mm Hg, after each treatment were calculated. These were then compared with
      placebo responses and expressed as dose-ratios. 4. Dose-ratios for finger tremor
      showed significant attenuation by all doses of betaxolol (compared with PL): B10
      1.5 +/- 0.18 (P less than 0.05), B20 2.62 +/- 0.45 (P less than 0.005), B40 2.55
      +/- 0.33 (P less than 0.001), B80 2.48 +/- 0.48 (P less than 0.01); and by P40
      6.49 +/- 1.12 (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1975197
TI  - Comparative beta-adrenoceptor blocking effects of propranolol, bisoprolol,
      atenolol, acebutolol and diacetolol on the human isolated bronchus.
AB  - Five beta-adrenoceptor blockers, propranolol, acebutolol, diacebutolol, atenolol
      and bisoprolol, were tested for their antagonistic effect against isoprenaline on
      human isolated bronchi. The results showed (1) that only propranolol exerted a
      competitive antagonistic effect against isoprenaline (pA2 = 9.40 +/- 0.22, n = 7)
      whereas the other drugs did not, and (2) that, in the presence of beta
      adrenoceptor blockers in the plasma concentrations reported after a single usual
      therapeutic dose, the doses of isoprenaline giving the same bronchodilator effect
      must be multiplied by 32.6, 5.51, 4.63, 2.82 and 1.95 respectively with
      propranolol, diacetolol, acebutolol, atenolol, and bisoprolol. It was concluded
      that (1) atenolol and bisoprolol were the least potent drugs at bronchial level
      in therapeutic plasma concentrations and (2) that tests performed on the human
      isolated bronchus might be a useful screening procedure for new drugs with
      potential activity on the airways.

PMID- 1975198
TI  - A comparison of the CNS effects of enprofylline and theophylline in healthy
      subjects assessed by performance testing and subjective measures.
AB  - 1. The effects of intravenous infusions of enprofylline, theophylline, and
      placebo on subjective ratings and on psychological test performance were studied
      in a double-blind crossover experiment in 12 healthy subjects who abstained from
      caffeine throughout the experimental procedures. 2. Mean plasma concentrations of
      enprofylline were: mean 2.9 mg l-1 (range 1.9-3.4). Those for theophylline were:
      mean 12.1 mg l-1 (range 9.0-14.4). 3. Performance on the auditory vigilance task
      showed a significant improvement with theophylline compared with both
      enprofylline and placebo. The correct detection rates (out of 90) were 50.3, 43.4
      and 39.1 respectively. A similar effect was seen with finger tapping rates: 404,
      394 and 390 taps min-1 respectively. Other measures showed no significant
      effects, although choice reaction time showed a trend towards faster responses
      with theophylline. 4. Subjective ratings showed that subjects were significantly
      more alert with theophylline than with enprofylline. Subjects reported themselves
      as significantly more dizzy and ill with both active drugs compared with placebo.
      5. These results suggest that emprofylline largely lacks the CNS stimulant
      effects of theophylline, but that the incidence of other unwanted effects of the
      drugs may be similar.

PMID- 1975201
TI  - Report from ASCO on taxol as second-line therapy for ovarian Ca.

PMID- 1975199
TI  - Pharmacological effects and pharmacokinetics of atipamezole, a novel alpha 2
      adrenoceptor antagonist--a randomized, double-blind cross-over study in healthy
      male volunteers.
AB  - 1. Single doses (10, 30 and 100 mg) of atipamezole (MPV-1248), a new potent and
      selective imidazole-type alpha 2-adrenoceptor antagonist, and saline placebo were
      administered as 20 min intravenous infusions to six healthy male volunteers in a
      randomized double-blind, cross-over phase I study. Later, 100 mg atipamezole was
      given orally to the same subjects in an open fashion. 2. The i.v. doses resulted
      in linearly dose-related concentrations of atipamezole in plasma. Pharmacokinetic
      calculations revealed an elimination half-life of 1.7-2.0 h, an apparent volume
      of distribution of 3.0-3.5 l kg-1 and a total plasma clearance of 1.1-1.5 l h-1
      kg-1. No atipamezole could be detected in plasma after oral dosing. 3. Subjective
      drug effects were seen mainly after the largest i.v. dose and included increased
      alertness and nervousness, coldness and sweating of hands and feet, tremor and
      shivering, motor restlessness, and increased salivation. Salivation was also
      quantitated using dental cotton rolls, with dose-related increases produced by
      the i.v. doses. 4. The 100 mg i.v. dose increased plasma noradrenaline
      concentrations on average by 484 +/- 269 (s.d.)%, and also elevated both systolic
      and diastolic blood pressure (mean increases 17 +/- 7/14 +/- 2 mm Hg). The 30 mg
      dose had minor and the 10 mg dose no effects on these variables. Adrenaline and
      cyclic AMP levels in plasma were increased only after the largest dose. No drug
      effects were observed after oral dosing. 4. Plasma C-peptide and blood glucose
      levels were not markedly influenced by the drug, and cortisol secretion was not
      stimulated. 5. The observed effects are compatible with the presumed alpha 2
      adrenoceptor antagonistic action of atipamezole and are in general concordance
      with the reported results of other alpha 2-adrenoceptor antagonists (yohimbine
      and idazoxan). 6. Although not orally active, atipamezole may prove to be a
      useful agent in studies of alpha 2-adrenoceptor function in man.

PMID- 1975200
TI  - Mequitazine in the treatment of hayfever.
AB  - A single-blind, multicentre, comparative clinical trial was performed in 59
      hayfever sufferers to compare the efficacy of mequitazine 5 mg bd and terfenadine
      60 mg bd over a period of 14 days. Clinical assessments of nasal and ocular
      symptoms were made on admission to the trial and after seven and 14 days
      treatment by both physicians and patients. Critical flicker fusion threshold was
      measured at each assessment. A global assessment of efficacy was determined by
      both the doctor and patient at the end of treatment. Patients also completed a
      daily diary card. Thirty patients on mequitazine and 22 on terfenadine completed
      the trial. There were seven dropouts (five on terfenadine and two on
      mequitazine). Both treatments were equally effective in reducing the severity of
      symptoms over the 14 days of treatment. The overall assessment at the end of
      treatment showed no important significant differences between the two drugs.
      According to the physicians, 60 per cent of the mequitazine-treated patients and
      63 per cent of the terfenadine-treated patients had an excellent or good
      response. Patients assessed their response as excellent or good in 56 and 62 per
      cent of cases respectively. Neither drug significantly impaired performance.

PMID- 1975202
TI  - Transport of the multidrug resistance modulators verapamil and azidopine in wild
      type and daunorubicin resistant Ehrlich ascites tumour cells.
AB  - Verapamil has been proposed to modulate the multidrug resistance phenotype by
      competitive inhibition of an energy dependent efflux of cytotoxic drug. However,
      the accumulation of both 14C-verapamil and 3H-verapamil was similar in wild type
      EHR2 and multidrug resistant EHR2/DNR+ Ehrlich ascites cells, and was much less
      in both cell lines in energy deprived medium than in medium containing glucose.
      Azidopine accumulation was also similar in both EHR2 and EHR2/DNR+ cells but, in
      contrast to verapamil, did not differ significantly with changes in cellular
      energy levels. Azidopine photolabelled a 170 kDa protein in EHR2/DHR+ plasma
      membrane vesicles which was immunoprecipitated by monoclonal antibody towards P
      glycoprotein. Azidopine increased daunorubicin accumulation and modulated
      vincristine resistance in EHR2/DNR+ cells in a similar fashion to verapamil.
      Azidopine photolabelling was inhibited by vincristine and verapamil, but not by
      daunorubicin. Vincristine, but not daunorubicin, was able to increase both
      azidopine and verapamil accumulation in EHR2/DNR+ cells only. Finally, though
      both verapamil and azidopine are a substrate for P-glycoprotein in EHR2/DNR+
      cells, they do not themselves appear to be transported by the multidrug
      resistance efflux mechanism to any significant extent in these cells.

PMID- 1975204
TI  - Intensive chemotherapy and autologous peripheral blood stem cell transplantation
      in a patient with persistent marrow involvement with Hodgkin's disease.
AB  - A patient with refractory Hodgkin's disease whose persistent, dense marrow
      infiltration precluded autologous marrow harvest underwent peripheral blood stem
      cell harvest followed by intensive chemotherapy and re-infusion of the peripheral
      blood stem cells. Complete remission was followed by relapse 6 months later and
      death 13 months post-transplant. However, at no time post-transplant was evidence
      of marrow recurrence demonstrated. This case indicates that remission can be
      achieved using peripheral blood stem cell transplants despite persistent marrow
      involvement with Hodgkin's disease.

PMID- 1975203
TI  - Chemosensitisation by verapamil and cyclosporin A in mouse tumour cells
      expressing different levels of P-glycoprotein and CP22 (sorcin).
AB  - The relationships between resistance to adriamycin, vincristine, colchicine and
      etopside, expression of P-glycoprotein and CP22 (sorcin), and resistance
      modification by verapamil and cyclosporin A have been studied in a panel of
      multidrug-resistant (MDR) mouse tumour cell lines. Whereas there was a generally
      good correlation between the degree of resistance and the amount of P
      glycoprotein, no relationship between resistance and CP22 expression was seen. At
      3.3 microM verapamil, the sensitisation of the MDR cell lines was no greater than
      that of the parent line. At 6.6 microM verapamil, however, sensitisation of the
      MDR lines generally exceeded that of the parent line, although the line CR 2.0,
      expressing very high levels of P-glycoprotein was an exception. Little
      sensitisation to etoposide was seen in any of the lines. When cyclosporin A was
      used as the sensitiser at either 2.1 or 4.2 microM, there was a greater effect in
      lines expressing moderate to high levels of P-glycoprotein than in the parent
      line, although this tendency was less for adriamycin than for the other
      cytotoxics. Sensitisation to etoposide was much greater with cyclosporin A than
      with verapamil. At low levels (less than 1 microM) of CsA, however, sensitisation
      to colchicine was greater in the parent line than in cell line CR 2.0. These
      studies indicate that chemosensitisation by verapamil and cyclosporin A is
      extremely complex, depending upon sensitiser dose, the particular cytotoxic and
      the cell line. At low doses of the sensitisers, the sensitisation may be greater
      in lines expressing low levels of P-glycoprotein than in lines showing high
      levels.

PMID- 1975205
TI  - Resistance to natural products in leukemia.

PMID- 1975206
TI  - Effects of butanedione monoxime on neuromuscular transmission.
AB  - 1. The amplitude of endplate potentials was increased by concentrations of
      butanedione monoxime (BDM, 5-20 mM) that typically caused muscle paralysis. 2.
      Although BDM slowed the decay of spontaneous miniature endplate currents, the
      effect was insufficient to explain most of the large increase in amplitude of
      endplate potentials. 3. The quantal content of endplate potentials was increased
      by BDM in a reversible, concentration-dependent manner. 4. The frequency of
      miniature endplate potentials was not changed by 10 mM BDM in the presence of
      normal or raised potassium concentrations, indicating that BDM does not change
      quantal content by a direct effect on calcium channels or on steady-state
      intracellular calcium concentration. 5. A change in the time course of the
      extracellularly recorded nerve terminal action potential caused by BDM was
      similar to the change produced by 4-aminopyridine (4-AP). 6. The increase in
      quantal content produced by BDM was only slightly reduced in the presence of 1 mM
      tetraethylammonium (TEA) but was significantly reduced in the presence of 0.5 to
      1 mM 4-AP. 7. It was concluded that BDM blocks a 4-AP-sensitive potassium
      conductance in motor nerve terminals and, by increasing the duration of the
      action potential in this way, increases evoked transmitter release.

PMID- 1975207
TI  - Action of noradrenaline on isolated proximal and distal coronary arteries of rat:
      selective release of endothelium-derived relaxing factor in proximal arteries.
AB  - 1. The effect of noradrenaline (NA) on the vascular smooth muscle and endothelial
      cells in isolated ring segments from the proximal and distal part of the left
      coronary artery (LCA) in rats was examined. 2. NA had a weak concentration
      dependent contractile effect on proximal but relaxed distal segments of the LCA.
      The maximal NA-induced contraction of the proximal segments was doubled while the
      relaxation of the distal LCA segments was converted to a contraction after
      blockade of beta-adrenoceptors with propranolol 3 x 10(-6) M, thus indicating the
      presence of both alpha- and beta-adrenoceptors in the arteries, with dominance of
      alpha-adrenoceptors and of beta-adrenoceptors in the proximal and distal segments
      of the LCA, respectively. 3. The contractile effect of NA (beta-adrenoceptors
      blocked) was doubled in the proximal LCA segments after the endothelium was
      removed. Endothelial denudation had, in contrast, no potentiating effect on the
      contractile response of the distal arteries to NA. Both proximal and distal
      segments became more sensitive to the contractile action of NA after removal of
      the endothelium. 4. The spontaneous myogenic tone increased in both proximal and
      distal LCAs after endothelial removal, indicating spontaneous release of a
      relaxing endothelial factor in the vessels. 5. Following contraction with
      prostaglandin F2 alpha (PGF2 alpha), and in the presence of propranolol, 3 x 10(
      6) M, and prazosin, 10(-6) M, NA induced an endothelium-dependent relaxation of
      only proximal but not distal segments of the precontracted LCA. The NA-induced
      relaxation of the proximal segments of the LCA was not altered by indomethacin 10
      M but was completely abolished after incubation with methylene blue, 3 x 10-6 M,
      or following endothelium removal. These results are compatible with NA-induced
      release of EDRF in these arteries. 6. The selective alpha 2-adrenoceptor agonist,
      B-HT 933, only induced a weak relaxation of PGF2 alpha,-precontracted proximal
      (endothelium intact) LCA segments at a concentration of 10-4M. The NA-induced
      relaxation of these vessels was unaffected by incubating the vessels with 10- IM
      B-HT 933. The NA relaxation response curve was shifted ca 1.1 log unit to the
      right by rauwolscine, 1o- 6M, giving an estimated pA2-value of 7.12. The receptor
      through which NA activates the endothelium appears to be of an atypical alpha 2
      subtype.

PMID- 1975208
TI  - Initial experience with percutaneous transluminal angioplasty in the management
      of Takayasu's arteritis.
AB  - We have performed percutaneous transluminal angioplasty (PTA) for 15 arterial
      stenoses in 11 patients with Takayasu's arteritis. The lesions included tight,
      proximally located renal artery stenosis (12 stenoses; nine patients), localized
      abdominal aortic stenosis (two patients) and occluded left common iliac artery
      (one patient). Clinically successful dilatation was achieved in seven patients
      (10 stenoses) with renal artery stenosis, in both the patients with abdominal
      aortic stenosis and in the only patient with an occluded left common iliac
      artery. No complications related to the procedure were encountered. The follow-up
      period (n = 7) ranged between 1 and 16 months, mean follow-up period after renal
      angioplasty was 5 months and after abdominal aortic angioplasty was 12.5 months.
      Initial success has been maintained in both the patients with abdominal aortic
      stenoses and in four out of five patients with renal artery stenosis.
      Percutaneous transluminal angioplasty offers an attractive alternative for the
      management of stenosing lesions in Takayasu's arteritis with good short term
      results.

PMID- 1975209
TI  - Relationship of primary site of testis to final testicular size in cryptorchid
      patients.
AB  - Testicular volume was examined in men who had undergone orchiopexy at or after 7
      years of age; 159 men with 187 cryptorchid testes were available for estimation.
      The mean age at orchiopexy was 9.8 years (range 7-13.6) and the mean age at
      follow-up was 24.3 years (range 18-41). The data showed that surgically treated
      cryptorchism was associated with testes that are significantly smaller than
      normal. The most important factor in relation to subsequent testicular size was
      whether or not the testes were palpable. Testes found in the superficial inguinal
      pouch were approximately 85% of normal testicular volume. Contralateral
      testicular volume in unilaterally cryptorchid patients was not significantly
      different from that of controls.

PMID- 1975210
TI  - Giant ureterocele--a rare presentation.

PMID- 1975211
TI  - Modulation by neuropeptides of bradykinin-stimulated second messenger release in
      dorsal root ganglion neurons.
AB  - Fetal rat dorsal root ganglion neurons (7-8 days in culture) were labeled with
      [3H]arachidonic acid for 24 h. Stimulation with 10 microM bradykinin (BK) for 30
      s resulted in nearly 2-fold increases in levels of radioactive diglyceride and
      arachidonic acid. A similar result was obtained in the absence of receptor
      stimulation using the Ca2+ channel agonist BAY K 8644 (10 microM, in the presence
      of 100 mM potassium chloride) or the Ca2+ ionophore, ionomycin (2.5 microM). If
      Ca2+ influx was inhibited by adding 3 mM Co2+, a blocker of voltage-sensitive
      calcium channels, or 2.5 mM EDTA, then BK-stimulated accumulation of both
      arachidonate and diglyceride was inhibited. These data suggest Ca2+ influx is
      required for ligand-stimulated accumulation of both arachidonate (a product of
      diglyceride-lipase or phospholipase A2) and diglyceride (a product of
      phospholipase C). Two distinct populations of channels may be involved in these
      reactions since pretreatment with 10 microM nifedipine or 50 microM verapamil
      (agents which block a subset of voltage-sensitive Ca2+ channels) inhibited BK
      stimulated accumulation of arachidonic acid, but did not inhibit diglyceride
      accumulation. Such functional discrimination appears to have physiological
      importance; the inhibitory effect of nifedipine and verapamil on BK-stimulated
      arachidonate release was mimicked by pretreatment with peptides which decrease
      Ca2+ channel conductance in dorsal root ganglion neurons. The three peptides used
      were 1 microM neuropeptide Y, 10 microM somatostatin, and 10 microM [N-MePhe3,D
      Pro4]-morphiceptin. The effect of neuropeptide Y was blocked by pretreatment with
      pertussis toxin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1975212
TI  - Masking effect of NMDA receptor antagonists on the formation of long-term
      potentiation (LTP) in superior colliculus slices from the guinea pig.
AB  - After electrical stimulation of the optic layer (OL) of superior colliculus (SC)
      slices, the postsynaptic potential (PSP) was recorded in the superficial gray
      layer (SGL) of the SC. The degeneration studies of retinotectal or corticotectal
      inputs to the SGL of the SC indicated that this PSP evoked in the SGL of the SC
      slices was retinotectal in origin. Neurotransmission in this pathway may be
      mediated by glutamate, because the PSP amplitude was reduced and blocked by
      application of kynurenate or quinoxaline dione (DNQX) to the medium. Furthermore,
      the concentration of glutamate in the right SGL was significantly reduced by 32%
      after left optic denervation and by 30% after ablation of the right visual
      cortex, compared with that in the left SGL. Long-term potentiation (LTP) in the
      SGL was induced by tetanic stimulation (50 Hz, 20 s) to the OL. The LTP formation
      was facilitated by the removal of Mg2+ from the medium. The effects of glutamate
      antagonists D-amino-5-phosphonovalerate (D-APV), gamma-D-glutamylglycine (gamma
      DGG), and (+)-5-methyl-10,11-dihydro-5H-dibenzo, a,d-cycloheptene-5,10-imine
      maleate (MK-801) on the induction of LTP were investigated. D-APV (100 microM) or
      gamma-DGG (1 mM) masked the expression of LTP by tetanic stimulation, however LTP
      was induced after removal of the agents. LTP formation was observed without
      further tetanic stimulation following the removal of D-APV from the medium even
      80 min after the tetanic stimulation. LTP once formed was not influenced by
      application of D-APV.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1975213
TI  - Modulation of acetylcholine release by D1, D2 dopamine receptors in rat striatum
      under freely moving conditions.
AB  - Using in vivo brain dialysis under freely moving conditions, we have studied the
      effects of dopamine (DA) agonists and antagonists on acetylcholine (ACh) and DA
      release in rat striatum. The striatal infusion of the D1 DA receptor specific
      agonist, SKF38393, increased striatal ACh release in a dose-dependent manner (10(
      6) to 10(-4) M), and 3 x 10(-5) M SKF38393 elicited a 60% augmentation in the
      level of ACh release. The level of ACh was increased with perfusion of 10(-4) M
      SCH23390, a D1 specific antagonist, but decreased with 10(-3) M SCH23390. The D2
      specific agonist, LY171555, and the antagonist, sulpiride, slightly altered the
      level of ACh in the striatum. On the other hand the level of DA dramatically
      increased in a dose-dependent manner with SKF38393 or SCH23390 and decreased with
      LY171555. LY171555 inhibited the effect of 10(-4) M SKF38393 on ACh release, and
      enhanced the effect of SKF38393 on DA release. These results suggest that the D1
      DA receptor mainly mediates ACh release and the D2 DA receptor modifies the
      effects of the D1 receptor.

PMID- 1975214
TI  - Evidence for spinal N-methyl-D-aspartate receptor involvement in prolonged
      chemical nociception in the rat.
AB  - Subcutaneous injection of formalin into the hindpaw peripheral receptive field of
      deep dorsal horn multireceptive (convergent) nociceptive neurones was used to
      produce a prolonged (1 h) activation of the cells. This chemical noxious stimulus
      produced a first peak of firing which lasted 10 min followed by a second peak of
      prolonged activity which was monitored for 50 min. gamma-D-glutamylglycine (DGG),
      a non-selective N-methyl-D-aspartate (NMDA) and quisqualate/kainate (non-NMDA)
      receptor antagonist was applied intrathecally both as a pretreatment and after
      the formalin. A complete abolition of both peaks of the formalin response was
      produced by DGG pretreatment (1000 micrograms) (n = 4). This dose produced
      profound inhibition of the acute C-fibre evoked responses of the same cells.
      However, no inhibitions were produced when the antagonist was applied once the
      formalin response had developed (n = 4). The selective NMDA receptor antagonist 5
      amino-phosphonovaleric acid (AP5) was administered intrathecally (250 and 500
      micrograms) as a 40 min pretreatment and caused a small inhibition of the first
      peak but a marked dose-related reduction in the second prolonged phase (n =7).
      AP5 did not influence the C-fibre inputs onto the cells. The non-competitive NMDA
      receptor channel blockers, ketamine and MK801, were administered i.v. during the
      second phase of firing. Ketamine (1-8 mg/kg) caused a short-lasting but marked
      and dose-related inhibition of the neuronal responses to formalin (n = 11). MK801
      (0.5-1 mg/kg) resulted in a prolonged inhibition of cell firing during the second
      phase of the response (n = 11).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1975215
TI  - Regulation of striatonigral prodynorphin peptides by dopaminergic agents.
AB  - The primary purpose of this study was to examine the regulation of prodynorphin
      peptides by dopaminergic agents in the central nervous system. The indirectly
      acting catecholamine agonist D-amphetamine sulfate (AMPH) and the dopamine
      receptor antagonist haloperidol (HAL) were administered to rats across a variety
      of treatment schedules and drug doses. The striatum, substantia nigra and
      hippocampus were dissected and examined by radioimmunoassay for 5 different
      prodynorphin peptides, covering all 3 opioid domains in the prodynorphin
      precursor: dynorphin A(1-8) and dynorphin A(1-17) of the dynorphin A domain,
      dynorphin B(1-13) of the dynorphin B domain, and alpha-neo-endorphin and beta-neo
      endorphin of the neo-endorphin domain. In addition, the proenkephalin peptide Met
      enkephalin-arg6-gly7-leu8 (MERGL) was examined in the striatum. AMPH administered
      one hour prior to sacrifice caused a dose-dependent depletion of prodynorphin
      peptides in both the striatum and substantia nigra. In animals treated with AMPH
      once each day for 7 days and sacrificed 24 h later, a dramatic dose-dependent
      increase in prodynorphin peptides was observed in these brain regions. Animals
      treated with AMPH once each day for 7 days and sacrificed one hour after the
      final injection showed no changes in prodynorphin peptides. In addition to
      changes in individual prodynorphin peptides, AMPH treatment caused alterations in
      the relationships between intermediate peptides (dynorphin A(1-17) and alpha-neo
      endorphin) and their immediate products (dynorphin A(1-8) and beta-neo
      endorphin). AMPH caused no consistent changes in prodynorphin peptides in the
      hippocampus, or in MERGL in the striatum. Taken together these data suggest that
      acute dopaminergic activation causes depletion of dynorphins from striatonigral
      prodynorphin neurons, presumably due to dopamine-dependent release of these
      peptides; repeated activation causes repeated release, with a rebound increase in
      biosynthesis. HAL, in contrast to AMPH caused relatively subtle changes in
      striatonigral prodynorphin peptides. Although no significant changes in
      individual prodynorphin peptides were observed, HAL treatment caused a change in
      the relationship between dynorphin A(1-17) and dynorphin A(1-8), a change
      opposite in direction to that observed with AMPH treatment. As has been
      previously reported, repeated HAL administration caused a dose-dependent increase
      in the proenkephalin peptide MERGL. The relatively subtle effects of HAL on
      prodynorphin peptides suggests that tonic dopamine activity is not important in
      the regulation of striatonigral prodynorphin neurons. The potential functional
      and behavioral significance of the present results are discussed.

PMID- 1975216
TI  - Selective release of N-acetylaspartylglutamate from rat optic nerve terminals in
      vivo.
AB  - Glutamate (Glu) and aspartate (Asp) are considered to be the neurotransmitters of
      the optic pathway in submammalian species, but their roles in mammals is
      uncertain. Recently, N-acetylaspartylglutamate (NAAG) has been proposed as a
      neurotransmitter in mammalian optic pathway; however, the release of endogenous
      NAAG on stimulation of the optic pathway has not been demonstrated. Using an in
      vivo microdialysis technique, we now report that electrical stimulation of rat
      optic nerve markedly increased the extracellular concentration of NAAG but not
      Glu/Asp in superficial superior colliculus where retinal afferents terminate,
      whereas non-specific stimulation of neurotransmitter release by high potassium or
      veratridine increased both extracellular Glu/Asp and NAAG concentration in the
      perfusate. The release of NAAG was dependent on Ca2+ and the presence of optic
      terminals. We conclude that NAAG is a better candidate as a neurotransmitter of
      rat optic nerve terminals than Glu/Asp.

PMID- 1975217
TI  - Effect of L-glutamate on the release of striatal dopamine: in vivo dialysis and
      electrochemical studies.
AB  - Microdialysis and in vivo voltammetry combined with K(+)-selective
      microelectrodes were utilized to study the effect of L-glutamate (GLU) on the in
      vivo release of dopamine (DA) from the rat striatum. Perfusion of 500 nM-5 mM GLU
      through the microdialysis probe was without an effect on DA outflow whereas 10 mM
      GLU resulted in a significant (295%) increase in the basal level of DA. This
      increase was blocked in the presence of 2-amino-5-phosphonopentanoic acid, an N
      Methyl-D-aspartate (NMDA) receptor antagonist. Repetitive local applications of
      10 mM GLU were also required to observe an increase in extracellular DA measured
      by in vivo voltammetry. These signals were accompanied with a massive increase in
      extracellular K+ and a large negative shift in the field potential resembling the
      ionic changes seen after the phenomenon spreading depression. These studies
      suggest that high concentrations of GLU are required to enhance the extracellular
      concentration of DA in vivo. Further, pathophysiological conditions such as
      spreading depression may be responsible for the observed increase in
      extracellular DA concentration.

PMID- 1975218
TI  - Histological and ultrastructural evidence that D-amphetamine causes degeneration
      in neostriatum and frontal cortex of rats.
AB  - D-Amphetamine sulfate, continuously administered for 3 days subcutaneously via an
      implanted minipump, induced neural degeneration in Long-Evans and Sprague-Dawley
      rats at doses between 20 and 60 mg/kg/day. Using Fink-Heimer silver staining,
      axonal degeneration was detected in the neostriatum and the dorsal agranular
      insular cortex and degenerating pyramidal cells were observed in portions of the
      somatosensory neocortex in both strains. In contrast, dense axonal degeneration
      largely confined to layers 2 and 3 of frontal motor areas (Fr1, Fr2 and Fr3 of
      Zilles36) with occasional degenerating cells was seen reliably in Long-Evans rats
      but rarely in Sprague-Dawley rats. In the electron microscope, cortical
      degeneration consisted mainly of disrupted cell bodies and dark processes,
      including axons making asymmetric synapses. Damage in all cortical areas
      represents damage to non-monoamine neurons and processes since tyrosine
      hydroxylase and serotonin immunolabeling were normal. In contrast, the damage in
      neostriatum probably includes damage to dopamine axonal terminals since tyrosine
      hydroxylase immunolabeling was patchy with many swollen and distorted labeled
      axons. Serotonin and Leu-enkephalin labeling were normal. Electron microscopy
      confirmed that the neostriatum contained many tyrosine hydroxylase-labeled axons
      that were swollen and disrupted, although other labeled processes made normal
      symmetric synapses onto spines and dendrites. Additional degeneration found only
      in amphetamine-treated rats included many dark, shrunken profiles. Some of these
      appeared to be astrocytic processes and a few were myelinated axons, suggesting
      that some non-monoamine, possibly cortical afferents, are also degenerating in
      the neostriatum. Since similar degrees of behavioral activation, weight loss and
      lethality were seen in both strains, a genetic predisposition constrain
      amphetamine-induced motor cortex damage but not neostriatal damage.

PMID- 1975219
TI  - Dopamine- and dopa-immunoreactive neurons in the cat forebrain with reference to
      tyrosine hydroxylase-immunohistochemistry.
AB  - The distribution of cell bodies containing immunoreactivities to dopamine (DA), L
      3,4-dihydroxyphenylalanine (DOPA) and tyrosine hydroxylase (TH) was studied
      immunohistochemically in the cat forebrain especially in the hypothalamus with or
      without intraventricular administration of colchicine. In normal cats, DA
      immunoreactive (IR) neurons, whose intensity of immunostainings was variable from
      one to another, were localized exclusively in the hypothalamus and showed a
      distribution pattern similar to that of TH-IR ones. They were distributed in the
      posterior, dorsal and periventricular hypothalamic areas. Arcuate cells showed no
      or very weak DA-immunoreactivity. Weak to intense DOPA-IR cells were distributed
      in a similar manner to DA-IR ones but were far smaller in number. In colchicine
      treated animals, DA- and DOPA-immunoreactivities were enhanced particularly in
      arcuate and dorsal hypothalamic cells. A cluster composed of small DA- and DOPA
      IR cells was identified in the area ventral to the mamillothalamic tract
      equivalent to rat A13c TH-IR cell group. Colchicine treatment enabled us to
      visualize a large number of TH-IR perikarya in the medial and lateral preoptic
      areas, anterior commissure nucleus, basal forebrain, area closely related to the
      organum vasculosum laminae terminalis, and some in the bed nucleus of the stria
      terminalis as has been reported in other species. However, virtually none of
      these cells contained detectable DA- and DOPA-immunoreactivities.

PMID- 1975220
TI  - [Preliminary establishment of hybridoma secreting monoclonal anti-idiotypic
      antibodies to hemorrhagic fever with renal syndrome virus].

PMID- 1975221
TI  - Benzodiazepines and synaptic processing in the spatial domain within the cat's
      primary somatosensory cortex.
AB  - In the primary somatosensory cortex of cats, the size of the receptive fields
      (RFs) of cutaneously responsive neurones is under the control of gamma
      aminobutyric acid (GABA) mediated inhibition when the cells are situated in
      rapidly adapting (RA) background regions. Cells located in slowly adapting (SA)
      or low-velocity rapidly adapting (LVRA) background regions do not appear to be
      affected by GABA significantly in the spatial domain, although other response
      properties such as threshold and firing pattern are under the influence of
      bicuculline methiodide (BMI) sensitive processes. The GABA receptor is one
      component of the oligomeric complex that includes the benzodiazepine (Bzd)
      binding site, the barbiturate recognition site, and the Cl- ionophore. Owing to
      current debates about the possible existence of endogenous ligands of Bzd
      receptors, we have examined whether Bzd agonists, in addition to GABA and BMI,
      have RF-modulating actions on RA S1 neurones and have assessed the effectiveness
      of the Bzd antagonist, Ro 15-1788, in this experimental paradigm. Ro 15-1788 is
      an imidazobenzodiazepine that acts as a specific competitive antagonist of Bzds
      by exerting high-affinity interactions with that Bzd receptor through which
      anticonvulsant effects of flurazepam (flu) and diazepam are expressed. This has
      been shown previously in neurochemical, behavioral, neurological, and
      pharmacological studies. Ro 15-1788 has little or no affinity for nonneuronal
      binding sites in the CNS. Ro 15-1788 binding does not displace GABA from its own
      binding site but does compete for all major Bzd ligands that act as
      pharmacological agonists and inverse agonists of the Bzd receptor through which
      anticonvulsant and convulsant effects are expressed. Bzd agonists elevated the
      threshold for somatic activation, depressed spontaneous activity, and decreased
      RF size. One exception in this regard was midazolam, which sometimes decreased
      somatic thresholds and increased spontaneous discharges. These latter effects
      were reversed at higher doses of the agonist. BMI returned RFs to control sizes
      when the drug was administered concurrently with Bzd agonists, or it caused RFs
      to assume greater than normal sizes, depending on the strength of current
      ejecting the antagonist. Ro 15-1788 given alone decreased response thresholds,
      increased spontaneous firing, and sometimes enlarged RFs. This antagonist also
      reversed the RF size-decreasing action of flu, diazepam, and midazolam.
      Quantitative analyses of air-puffer responses evoked from low-threshold, S1 cells
      revealed that Bzds do not selectively attenuate spatial summation, but that they
      act preferentially in the surround, or in the peripheral, regions of cutaneous
      excitatory RFs.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1975222
TI  - [Progression of pathology of the diffuse endocrine system].

PMID- 1975223
TI  - [Immunocytochemical study of enterochromaffin cells in carcinoma of the large
      intestine].
AB  - In a series of 130 cases of adenocarcinoma of the large intestine,
      enterochromaffin (EC) cells were detected in 54 cases (41.5%) by
      immunocytochemistry with anti-chromogranin monoclonal antibody. Among the 54
      cases, 30 were found positive for serotonin, 14 for somatostatin, 11 for
      glucagon, 5 for pancreatic polypeptide, and only one for gastrin. The cases with
      EC cells (++) or polypeptide positive cells exhibited higher grade of
      differentiation, earlier stage of tumour extension and higher survival rate than
      those without EC cells. A significant difference of the EC cell population
      pattern among different histological grades of the tumours and nonneoplastic
      mucosa was found. The proportion of hormone, especially polypeptide positive
      cells was the highest in the mucosa and lowest in the moderately poorly
      differentiated carcinomas. The incidence, methodology and clinicopathological
      significance of EC cells found in the tumours are discussed.

PMID- 1975224
TI  - [Analysis of mononuclear cell subsets infiltrated and DR-positive epithelial
      cells in autoimmune thyroid diseases].
AB  - Specimens of thyroid tissue from 37 cases of autoimmune thyroiditis (AT), 13
      cases of thyrotoxicosis accompanied with thyroiditis (TTOT), and 23 cases of
      Graves' disease (GD) were analyzed by immunohistochemistry with monoclonal
      antibodies. The majority of infiltrating mononuclear cells were learnt to be T
      cells. T+4 cells were abundant in lymphoid follicles and many T+8 cells were
      noticed in those areas with advanced destruction. B lymphocytes were
      predominantly located at the germinal centers. Most importantly, DR-positive
      thyroid epithelial cells were significantly increased with intense lymphocytes
      infiltration and severe destruction of the thyroid architecture. The percentage
      of T cell subpopulations, B cells, macrophages were somewhat similar. Anyhow, the
      increase of total number of infiltrating cells and the extent of inflammatory
      injury were remarkable in GD, TTOT and AT. The results support the idea that some
      GD cases may further develop in to autoimmune thyroiditis later.

PMID- 1975226
TI  - F(ab')2 anti-CD4 and intact anti-CD4 monoclonal antibodies inhibit the
      accumulation of CD4+ T cells, CD8+ T cells, and B cells in the kidneys of lupus
      prone NZB/NZW mice.
AB  - Murine lupus in NZB/NZW (B/W) mice is characterized by immune-complex
      glomerulonephritis and lymphocytic infiltration of several organs, including the
      kidney. We recently showed that treatment of B/W mice with F(ab')2 anti-CD4
      monoclonal antibody retards autoimmunity by inhibiting the function of CD4+ cells
      and not by depleting them. To determine if treatment with F(ab')2 anti-CD4
      prevented lymphocytic infiltration of kidneys or simply inhibited the function of
      the infiltrating lymphocytes, long-term survivors of treatment with F(ab')2 anti
      CD4 and intact anti-CD4 were sacrificed for immunohistochemical analysis of their
      kidneys. Untreated B/W mice had large lymphocytic aggregates under the surface
      epithelium of the renal calyces. Most of these lymphocytes were CD4+ T cells, but
      CD8+ T cells and B cells were also present. In contrast, treatment with either
      intact anti-CD4 or F(ab')2 anti-CD4 substantially reduced, and in many cases
      prevented, the development of renal infiltrates. Treatment with either form of
      anti-CD4 not only inhibited renal infiltration by CD4+ T cells, but also
      prevented the accumulation of CD8+ T cells and B cells. These observations
      suggest a role for the CD4+ T cell in the accumulation of lymphocytes in target
      organs.

PMID- 1975225
TI  - Relationship between systemic and coronary vascular responses to digoxin and
      concurrent drug therapy with verapamil/beta-adrenoceptor antagonists in humans.
AB  - 1. In 24 patients who were undergoing coronary arteriography for the assessment
      of ischaemic heart disease, the relationship between the systemic and coronary
      vascular responses to acute intravenous digoxin administration (500 micrograms)
      and concurrent drug therapy with the calcium antagonist verapamil (group I) or a
      beta-adrenoceptor antagonist (group II) or neither of these agents (group III)
      was examined. 2. Systemic vascular resistance (SVR) tended to rise rapidly after
      digoxin injection in patients in groups II and III, and tended to decline
      initially in patients in group I; however, these differences were not
      statistically significant (variance ratio [VR] = 0.77). 3. No significant
      differences were observed in coronary vascular responses to acute digoxin
      administration between the three groups of patients (VR = 0.34). 4. For the
      entire group of 24 patients, no statistically significant digoxin-induced effects
      on resistance could be demonstrated in either the systemic or coronary
      circulations, although in individual patients vasoconstrictor effects were
      observed. 5. We conclude that acute intravenous administration of digoxin does
      not consistently cause systemic or coronary vasoconstriction in patients with
      ischaemic heart disease. Variability in vasomotor responses to digoxin is not
      clearly related to concurrent drug therapy with verapamil or a beta-adrenoceptor
      antagonist. The observation that systemic vascular resistance tends to increase
      in the first few minutes after digoxin injection should be addressed in future
      studies.

PMID- 1975227
TI  - Glutamine metabolism in skeletal muscle of glucocorticoid-treated rats.
AB  - 1. The effect of dexamethasone (30 micrograms day-1 100 g-1 body weight) on the
      regulation of glutamine metabolism was studied in skeletal muscles of rats after
      9 days of treatment. 2. Dexamethasone resulted in negative nitrogen balance, and
      produced increases in the plasma concentrations of alanine (23.4%) and insulin
      (158%) but a decrease in the plasma concentration of glutamine (28.7%). 3.
      Dexamethasone treatment increased the rate of glutamine production in muscle,
      skin and adipose tissue preparations, with muscle production accounting for over
      90% of total glutamine produced by the hindlimb. 4. Blood flow and arteriovenous
      concentration difference measurements across the hindlimb showed an increase in
      the net exchange rates of glutamine (25.3%) and alanine (90.5%) in dexamethasone
      treated rats compared with corresponding controls. 5. Dexamethasone treatment
      produced significant decreases in the concentrations of skeletal muscle glutamine
      (51.8%) and 2-oxoglutarate (50.8%). The concentrations of alanine (16.2%),
      pyruvate (45.9%), ammonia (43.3%) and inosine 5'-phosphate (141.8%) were
      increased. 6. The maximal activity of glutamine synthetase was increased (21
      34%), but there was no change in that of glutaminase, in muscles of dexamethasone
      treated rats. 7. It is concluded that glucocorticoid administration enhances the
      rates of release of both glutamine and alanine from skeletal muscle of rats (both
      in vitro and in vivo). This may be due to changes in efflux and/or increased
      intracellular formation of glutamine and alanine.

PMID- 1975229
TI  - Endoscopic lithotripsy of gastric bezoars using a laser-ignited mini-explosive
      device.
AB  - This paper reports the successful experiences of in vitro and in vivo studies on
      endoscopic fragmentation of gastric bezoars using a laser-ignited mini-explosive
      device. This new technique has been used clinically in 31 patients with gastric
      bezoars since January 1988. All patients were completely cured without any
      complication. The relationship between gastric bezoars and ulcers, and the
      technique of treatment were discussed.

PMID- 1975228
TI  - Chicken growth hormone: cDNA-synthesis and base sequence.
AB  - 1. Growth hormone (GH)-cDNA was synthesized from poly A(+)-mRNA extracts of
      chicken pituitary glands. 2. Chicken-cDNA library was cloned into E. coli. 3.
      Base sequence analysis of chicken GH-cDNA revealed only 70% similarity compared
      with duck GH-cDNA, and 97% similarity with a previously published chicken GH-cDNA
      sequence. 4. Dissimilarities in base sequences are primarily observed in the 3'
      non-coding region of GH-cDNAs (chicken and duck). 5. Comparisons of amino acid
      sequences of chicken and duck GH exhibit only three substitutions, while the
      amino acid sequences of GHs of chicken are identical.

PMID- 1975230
TI  - Epidemic hemorrhagic fever. The mechanism of coagulation and fibrinolysis.
AB  - To understand the mechanism of hemorrhage, coagulation and fibrinolysis in
      epidemic hemorrhagic fever (EHF), thrombin time (TT), prothrombin time (PT),
      fibrinogen (FIG), the platelet count (PLAT), plasminogen (PLG), antithrombin-III
      (AT-III), fibrin-fibrinogen degraded products (FDP) and platelet functions of
      aggregation and release were studied dynamically with advanced methods in 134 EHF
      patients. TT and PT were prolonged, FIG, AT-III and PLG were decreased and FDP
      was increased. Besides, the decrease of PLAT, the platelet functions of
      aggregation and release were below the normal level. The results showed that the
      balance of blood coagulation and fibrinolysis was lost from the early stage of
      the disease.

PMID- 1975231
TI  - [Drug abuse among residents of Beijing: an epidemiologic survey of 1,822
      households].
AB  - An epidemiological survey was conducted in the residential areas of 6
      neighbourhood committees of Chao Yang District of Beijing in search of the
      prevalent status and related factors of drug abuse among 1,822 households out of
      6,114 population. The result of present study reveals that the prevalence rate of
      limit daily-used drug abuse is 3.09% among a sample of 5,509 people over the age
      of fifteen. However, the extent of drug abuse seems neither great nor epidemic
      and all 17 dependents living in scattered geographical sites. In exploring the
      causation of drug abuse, the authors found that family structure, economic
      status, individual social function or stressful life events are not correlated
      and the use of drug is not a coping method to environmental maladaptation. On the
      contrary, most of the drug dependent are attributable to some iatrogenic reasons
      lacking of certain drug monitoring measures in their long-term medication. In a
      word, the misuse of drug facilitated addictive behaviors. No social problem
      emerged among all cases of study as measured with SDSS, but it is still a
      potential hazard to the psychosomatic health condition in the long run.

PMID- 1975232
TI  - [Mononuclear cell subsets in the peripheral blood of patients with myasthenia
      gravis].
AB  - With the use of the Wuhan series of monoclonal anti-lymphocyte antibodies, the
      peripheral blood mononuclear cell subpopulations in 104 patients with myasthenia
      gravis were studied. Before treatment, the mean T4/T8 ratio was higher and the
      percentage of WuT8+ cells (suppressor T cells) was lower in patients than in the
      controls. Furthermore, they also showed a higher number of B cells and abnormal
      lymphocytes (including immature thymocytes and Tac cells) in the blood. In this
      series 50 cases after oral prednisone treatment and 10 cases following thymectomy
      revealed normal ranges of mean T4/T8 ratio and WuT8+ cells. Besides, the number
      of B cells and immature thymocytes in them reduced significantly.

PMID- 1975233
TI  - Evaluation of polymorphic genetic markers for linkage to the familial adenomatous
      polyposis locus on chromosome 5.
AB  - A gene associated with the inherited syndrome, familial adenomatous polyposis
      (FAP), has been localized to the long arm of chromosome 5 near the 5q21-22
      region, and markers that identify genetic polymorphisms near this locus are now
      available. The authors evaluated several of these markers for linkage to the FAP
      trait in 11 families entered in the Cleveland Clinic Polyposis Registry. The
      original probe that established linkage to the FAP locus (C11p11) has limited
      utility for family studies because of low heterozygosity and distance from the
      FAP gene. Other probes, however, should be useful for assessing FAP inheritance
      by restriction fragment length polymorphism analysis, for presymptomatic
      diagnosis of the disease.

PMID- 1975234
TI  - [Sleep and sleep disorders].

PMID- 1975235
TI  - [Sleep in old age].

PMID- 1975236
TI  - [The differential therapy of chronic heart failure].

PMID- 1975237
TI  - Future trends in the pharmacological treatment of smoking cessation.

PMID- 1975238
TI  - Fimbrial phase variation in Bordetella pertussis: a novel mechanism for
      transcriptional regulation.
AB  - Fimbriae belong to a class of extracellular filamentous proteins which are
      involved in the attachment of bacteria to host tissues. Bordetella pertussis, the
      etiological agent of whooping cough, produces two serologically distinct
      fimbriae. We show that, like a number of other B. pertussis virulence genes,
      transcription of the fimbrial subunit genes (fim) is positively controlled by
      trans-acting polypeptides encoded by the bvg locus. In addition to this
      coordinate control, transcription of the fim genes is regulated at an individual
      level by phase variation. This process is characterized by a switching between a
      high and low level of expression of a particular fim gene. We have identified a
      conserved DNA region, located close to the start of the fim genes, which is
      likely to be involved in both positive regulation by the bvg locus, and phase
      variation. This promoter region contains a stretch of approximately 15 C residues
      and it appears that phase transitions occur by small insertions or deletions in
      this C-rich region. We propose that these mutations affect transcription of the
      fim genes by varying the distance between the binding site for an activator and
      the -10 box. The fim promoter shows homology with the pertussis toxin promoter,
      which is also positively regulated by the bvg locus.

PMID- 1975239
TI  - Molecular analysis of the bicoid gene from Drosophila pseudoobscura:
      identification of conserved domains within coding and noncoding regions of the
      bicoid mRNA.
AB  - The specification of anterior positional information during Drosophila
      embryogenesis is largely dependent upon the function of the maternal-effect gene
      bicoid (bcd). Two aspects of bcd function are particularly striking. First, the
      bcd protein product forms a gradient during early embryogenesis, which regulates
      the transcription of at least one zygotic segmentation gene, hunchback, in a
      concentration dependent manner. Secondly, formation of the bcd protein gradient
      is dependent upon the specific localization of bcd mRNAs at the anterior end of
      the oocyte/embryo during oogenesis, a process which requires a cis-acting 625
      nucleotide sequence within the 3' untranslated region of the bcd mRNA. We have
      cloned and sequenced the bcd gene from Drosophila pseudoobscura as a tool in
      identifying important functional domains within this transcription unit. DNA
      sequence comparisons reveal: (i) varying degrees of amino acid sequence
      conservation among the proposed functional domains of the bcd protein, (ii) the
      conservation of potential RNA secondary structures within the bcd mRNA
      localization element, and (iii) the maintenance of a short open reading frame
      within the 5' untranslated leader that may play a role in translational
      regulation. Finally, the D.pseudoobscura bcd gene partially rescues the phenotype
      of a bcd- mutation when placed into the D.melanogaster genome by germline
      transformation. The lack of full phenotypic rescue can be explained in part by
      the observed improper localization of the D.pseudoobscura bcd mRNA when expressed
      in D.melanogaster.

PMID- 1975241
TI  - Structure of the arylsulfatase A gene.
AB  - A 14-kb genomic clone containing the entire gene of human lysosomal arylsulfatase
      A was isolated. The arylsulfatase A gene is about 3.2 kb long and has eight exons
      (103-320 nucleotides in size). All intron-exon splice junctions conformed to the
      GT/AG consensus sequence. S1 nuclease mapping shows multiple transcription
      initiation sites between nucleotides -367 and -387. A fragment encompassing 360
      nucleotides of the flanking sequence upstream of the transcription initiation
      site shows promoter activity when it was transiently expressed in COS cells using
      the gene for bacterial chloramphenicol acetyltransferase as a reporter gene. This
      putative promoter region shows four potential Sp1 binding sites but lacks typical
      TATA and CAAT box sequences. Three different mRNA species of 2.1, 3.7 and 4.8 kb
      are transcribed from the gene and arise probably from the use of different
      polyadenylation signals.

PMID- 1975240
TI  - Phorbol esters induce differentiation of U-937 human promonocytic cells in the
      absence of LFA-1/ICAM-1-mediated intercellular adhesion.
AB  - Intercellular adhesions which occur during the mononuclear phagocyte
      differentiation are predominantly mediated by the lymphocyte-function-associated
      antigen-1 (LFA-1) family and the intercellular-adhesion molecule-1 (ICAM-1) which
      is a ligand for LFA-1. Thus, differentiation of U-937 promonocytic cells induced
      by phorbol esters occurs concomitantly with intercellular LFA-1/ICAM-1-dependent
      cluster formation. Since these homotypic adhesions can be inhibited by monoclonal
      antibodies (mAb) directed to either LFA-1 or ICAM-1, we have analyzed whether the
      lack of cell-cell adhesions impairs the differentiation process. Treatment of U
      937 cells with the phorbol ester 12-O-tetradecanoylphorbol 13-acetate in the
      presence of mAb to LFA-1 or ICAM-1 antigens yielded cells free from homotypic
      adhesions but differentiated as evidenced by their decreased proliferation and
      enhanced capacity for generation of superoxide anion. In addition, expression of
      the CD11c antigen was increased, whereas the transferrin receptor disappeared
      from the cell surface. Vimentin gene transcription was also greatly augmented as
      opposed to a clear diminution in the levels of c-myc and ornithine decarboxylase
      transcripts. These results clearly demonstrate that phorbol esters can induce
      differentiation of monocytic cells independently of cell-cell adhesion.

PMID- 1975242
TI  - The phenotypic response of cultured quail trunk neural crest cells to a
      reconstituted basement membrane-like matrix is specific.
AB  - Previous work has demonstrated that a reconstituted basement membrane (RBM)-like
      matrix stimulates the development of catecholamine (CA)-containing cells in
      neural crest cultures. In the present work, we found that the proportion of
      tyrosine hydroxylase and somatostatin immunoreactive cells was increased
      substantially by an overlay of the RBM matrix. In contrast, there was little or
      no stimulation of the development of cells possessing several other phenotypic
      markers including A2B5, E/C8, vasoactive intestinal polypeptide, and the low and
      middle molecular weight avian neurofilament proteins. These results demonstrate
      that the response of neural crest cells to the RBM matrix is specific to a small
      set of phenotypes. In addition, we demonstrate that the phenotype of the
      adrenergic cells which develop in the presence of the RBM gel overlay is very
      similar, if not identical, to that of the adrenergic cells which differentiate in
      the absence of the RBM gel.

PMID- 1975243
TI  - Increased expression of T alpha 1 alpha-tubulin mRNA during collateral and NGF
      induced sprouting of sympathetic neurons.
AB  - We have examined expression of T alpha 1 alpha-tubulin mRNA in the rat superior
      cervical ganglion (SCG) to determine whether changes in gene expression accompany
      neuronal sprouting and to investigate factors that regulate growth-associated
      genes in intact neurons. Northern blot analysis demonstrates that levels of T
      alpha 1 alpha-tubulin mRNA increase in the uninjured SCG following transection of
      contralateral neurons that project to bilaterally innervated, but not
      unilaterally innervated target organs. The observed increase in uninjured neurons
      is associated with collateral sprouting, as measured by increased tyrosine
      hydroxylase immunoreactivity within the pineal gland. These data suggest that
      target-derived factors may regulate T alpha 1 mRNA in sprouting neurons.
      Consistent with this hypothesis, systemic NGF treatment of neonatal animals over
      a developmental interval when T alpha 1 alpha-tubulin mRNA normally decreases led
      to a 5- to 10-fold increase in T alpha 1 mRNA levels in developing sympathetic
      neurons. In addition, deafferentation of the SCG, which promotes neuronal
      sprouting in the ganglion, increases T alpha 1 mRNA in ganglia on the ipsilateral
      and contralateral sides. Together, these data demonstrate that T alpha 1 alpha
      tubulin mRNA elevates as a function of neuronal sprouting, and that T alpha 1
      mRNA expression in intact neurons can be regulated by extrinsic cues, including
      NGF and changes in connectivity.

PMID- 1975244
TI  - Effects of beta-blocking agents on insulin secretion and glucose disposal.
AB  - Non-selective and to a lesser extent selective beta-blockers are known to
      slightly deteriorate glucose metabolism. This may be of clinical relevance, since
      patients with essential hypertension suffer from reduced insulin-sensitivity and
      some studies showed an increased incidence of diabetes type II with beta-blocker
      treated hypertensive patients. However, it is not clear whether this effect is
      due to hypertension per se or in addition by antihypertensive treatment. The
      possible mechanisms by which beta-blockers influence carbohydrate metabolism are
      discussed. Insulin secretion is inhibited by beta-blockers in vitro. However, no
      effect is seen in vivo in man. Hepatic glucose production in theory may be
      influenced, but no effect is demonstrable. Muscular glucose uptake could be
      reduced; some data exist showing reduced peripheral insulin sensitivity, although
      there are controversial results. In conclusion, a deterioration of carbohydrate
      metabolism by beta-blockers is established, the mechanism whereby remains
      obscure.

PMID- 1975245
TI  - Incidence of diabetes during antihypertensive treatment.
AB  - A prospective population study of women in Gothenburg, Sweden, showed an
      increased risk of developing diabetes in women taking diuretics or beta-blockers
      as antihypertensive agents compared to other women. The risk seemed to be still
      higher, if the combination of diuretics and beta-blockers was used. The same
      observation was made also when the study was confined to hypertensive women
      indicating that not only the hypertensive state but also the antihypertensive
      drugs per se may be a risk factor for developing diabetes. This possibility is
      further strengthened by the fact that, as far as diabetes type II is concerned,
      the hypertensive state in most cases precedes the development of diabetes, while
      only few subjects with diabetes type II develop arterial hypertension. We could
      only study the possible diabetic effect of diuretics and beta-blockers. It must,
      however, be of great interest to study alpha-blockers, calcium antagonists and
      ACE inhibitors in the same way. If one or more of these new substances will prove
      not to be diabetogenic, this will be a very important factor in our choice of
      first drug in the treatment of arterial hypertension.

PMID- 1975246
TI  - Effects of alpha and beta adrenoceptor blocking drugs and ACE inhibitors on long
      term glucose and lipid control in hypertensive non-insulin dependent diabetics.
AB  - Long-term glycaemic control measured by glycosylated haemoglobin concentration
      was compared in hypertensive NIDD's taking placebo, alpha-blockers, beta-blockers
      (alone and in combination) and an ACE inhibitor (enalapril) each for 4 months.
      Alpha-blockade caused no deterioration in long-term glycaemic control in NIDD's.
      Beta-blockers caused a deterioration in glycaemic control in NIDD's (with some
      adverse effects on lipid profile). This was especially apparent with the
      lipophilic beta-blocker P. Concurrent use of an alpha-blocker with a beta-blocker
      prevents the deterioration due to beta-blockade. The ACE inhibitor, enalapril
      caused an improvement in long-term glycaemic control without alteration of lipid
      control in NIDD's.

PMID- 1975247
TI  - HLA phenotypes and gene polymorphisms in juvenile liver disease associated with
      alpha 1-antitrypsin deficiency.
AB  - Chronic liver disease affects up to 20% of children with alpha 1-antitrypsin
      deficiency owing to the PiZZ genotype. Previous observations of a familial
      occurrence and abnormal immune responses to liver antigens in these patients
      suggests that immunoregulatory genes may be involved in the pathogenesis of liver
      damage. We have identified HLA phenotypes and class II (HLA-DR) gene
      polymorphisms in 140 white PiZZ subjects, of whom 92 (83 index patients) had
      liver disease, and 206 first-degree relatives. DR3* was present in 35 of 75
      (46.7%) unrelated patients with liver disease compared with 5 of 28 (17.8%)
      patients without (p less than 0.01) and 23 of 100 controls (p less than 0.001).
      DR4 was increased in patients without liver disease; it was present in 17 of 28
      (60.7%) compared with 29 of 75 (38.7%) patients with liver disease (p less than
      0.05) and 36 of 100 controls (p less than 0.025). Using Southern blot analysis
      with HLA-DRB and DQB DNA probes, we identified two polymorphisms of DR3, only one
      (Dw25) of which is raised in PiZZ individuals with liver disease (9 of 55: 16.4%)
      compared with 1 of 23 (4.4%) without and 2 of 52 (3.9%) controls (p less than
      0.05). Analysis of the segregation of HLA haplotypes in 77 families revealed no
      concordance for liver disease with HLA in those with affected sibships,
      indicating that, although DR3-Dw25 is associated with liver disease in alpha 1
      antitrypsin deficiency, other factors must play a pathogenic role.

PMID- 1975248
TI  - Changes in brain metabolism during hyperammonemia and acute liver failure:
      results of a comparative 1H-NMR spectroscopy and biochemical investigation.
AB  - The effects of hyperammonemia on brain function have been studied in three
      different experimental models in the rat: acute liver ischemia, urease-treated
      animals and methionine sulfoximine-treated animals. To quantify the development
      of encephalopathy, clinical grading and electroencephalographic spectral analysis
      were used as indicators. In all three experimental models brain ammonia
      concentrations increased remarkably associated with comparable increases in
      severity of encephalopathy. Furthermore, in vivo 1H-nuclear magnetic resonance
      spectroscopy of a localized cerebral cortex region showed a decrease in glutamate
      concentration in each of the aforementioned experimental models. This decreased
      cerebral cortex glutamate concentration was confirmed by biochemical analysis of
      cerebral cortex tissue post mortem. Furthermore, an increase in cerebral cortex
      glutamine and lactate concentration was observed in urease-treated rats and acute
      liver ischemia rats. As expected, no increase in cerebral cortex glutamine was
      observed in methionine sulfoximine-treated rats. These data support the
      hypothesis that ammonia is of key importance in the pathogenesis of acute hepatic
      encephalopathy. Decreased availability of cerebral cortex glutamate for
      neurotransmission might be a contributing factor to the pathogenesis of
      hyperammonemic encephalopathy. A surprising new finding revealed by 1H-nuclear
      magnetic resonance spectroscopy was a decrease of cerebral cortex phosphocholine
      compounds in all three experimental models. The significance of this finding,
      however, remains speculative.

PMID- 1975249
TI  - Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) treatment in vivo on
      thymocyte functions in mice after activation in vitro.
AB  - Thymocytes from 15-day old C57BL/6 mice, pretreated with 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) 4 days before sacrifice, showed an earlier
      response and a higher maximal cell proliferation than thymocytes from control
      mice upon stimulation by concanavalin A in vitro. This is partly in contrast to
      the conclusions from earlier published studies. IL-2 content--as measured by
      growth of CTLL cells--was equally high in TCDD and in control cultures at day 1.
      At day 2, TCDD cultures had decreased dramatically in IL-2 content, possibly due
      to a high rate of consumption. At this point in time, the controls still
      contained a high concentration of IL-2, although less than at day 1. In contrast
      to the increased sensitivity to mitogen stimulation, thymocytes from TCDD-treated
      mice induced B-cells less avidly with respect to antibody production, and could
      also inhibit the T-cell help of thymocytes from untreated animals, a phenomenon
      which could be reversed if TCDD-treated thymocytes were irradiated before
      culture.

PMID- 1975250
TI  - Myositis ossificans in tetanus. A rare complication.
AB  - Myositis ossificans developing as a complication of tetanus is very rare. There
      are only nine cases reported so far. We report here a case of a young female who
      developed myositis ossificans in both the elbow joints as a complication of
      severe tetanus.

PMID- 1975251
TI  - Subpopulations of endosomes generated at sequential stages in the endocytic
      pathway of asialoganglioside-containing ferrite ligands in rat liver.
AB  - Subpopulations of endosomes generated at different stages of the endocytic
      pathway were isolated by a high-gradient magnetic separation followed by a
      Percoll density gradient centrifugation. Rat livers were perfused for 5 min with
      asialoganglioside (ASG)-containing ferrite particles and chased at 37 degrees C.
      At various times after the internalization, the endocytic vesicles containing
      ferrite particles were isolated by the magnetic separation. Isolated fractions
      contained endosomes until 15-min perfusion, after which most of the particles
      were transported to lysosomes. The endosomal fractions isolated after the 5- or
      15-min perfusions were further analyzed by 30% Percoll density gradient
      centrifugation. The endosomes after 5-min perfusion showed peaks around the
      density of 1.05 g/ml (peak I) and 1.07 g/ml (peak Is), both of which contained
      asialoglycoprotein receptors. In the 15-min perfusion, another peak of endosomes
      (peak II) was observed at the higher density of 1.09 g/ml without the receptors,
      in addition to peak I. These endosomes had their own characteristic proteins.
      Some proteins were common in the subgroups of endosomes. These results suggest
      that the endosome I containing the ligands and the receptors was first produced
      after endocytosis and, through the endosome is, was scissioned into the endosome
      II containing the ligands. The endosome II was then fused with primary lysosomes
      for proteolytic cleavage of ligands.

PMID- 1975252
TI  - Absence of H-ras point mutation at codon 12 in N-methyl-N-nitrosourea-induced
      hepatocellular neoplasms in the rat.
AB  - In order to assess the possibility that activated ras-associated hepatic
      carcinomas might be much rarer in rats than mice because of the more frequent or
      rapid occurrence of powerful carcinogenic event(s) other than ras point mutations
      in the former animals, precancerous lesions and hepatocellular carcinomas induced
      by a weak hepatocarcinogen N-methyl-N-nitrosourea (MNU) in the rat liver were
      analyzed for the presence or absence of ras point mutations. MNU was chosen
      because it is well known that MNU-induced rat mammary carcinomas contain
      activated H-ras at very high frequency. Male Fisher rats were treated with a
      single dose of MNU after partial hepatectomy, and then administered dietary
      phenobarbital or repeated s.c. injections of carbon tetrachloride as promoting
      procedures. Analyses by oligonucleotide hybridization, MnlI-restriction-fragment
      length polymorphism and NIH3T3 cell transfection assays revealed neither H-ras
      point mutations nor transforming ability of the DNA from 36 MNU-induced rat
      hepatic neoplasms. The results were in agreement with previous results for rat
      hepatocellular carcinomas induced by other potent liver carcinogens and did not
      support our hypothesis that the frequency of finding ras activation might be
      dependent on the strength of the carcinogen.

PMID- 1975254
TI  - Perspectives in cancer prevention. Report on the eighth annual ECP symposium.

PMID- 1975253
TI  - Effect of dietary vitamin E on the development of altered hepatic foci and
      hepatic tumors induced by the peroxisome proliferator ciprofibrate.
AB  - The purpose of this study was to determine the effect of the dietary antioxidant
      vitamin E on hepatocarcinogenesis by peroxisome proliferators which, it is
      hypothesized, induce tumors by increased production of hydrogen peroxide or other
      oxygen radicals. Rats were fed diets containing the peroxisome proliferator
      ciprofibrate and one of three concentrations (10, 50, or 500 ppm) of alpha
      tocopheryl acetate for 6 months or 21 months. The incidence of hepatic tumors and
      the number and volume of gamma-glutamyl-transpeptidase-positive, ATPase-negative,
      glucose-6-phosphatase-negative, and glucose-6-phosphatase-positive foci were
      quantified. No tumors or altered hepatic foci were seen at 6 months, but at 21
      months the incidence of hepatic tumors and the number and volume of altered
      hepatic foci were increased in rats fed higher levels of vitamin E. Indices of
      oxidative damage--concentrations of malonaldehyde, conjugated dienes, and lipid
      soluble fluorescence products--were not affected or were lower in rats fed higher
      amounts of vitamin E; the enhancing effect of vitamin E on the development of
      altered hepatic foci and hepatic tumors, therefore, was not related to the
      induction of cellular oxidative damage. Hepatic peroxisomal fatty acid beta
      oxidation and vitamin C concentrations were not affected by vitamin E, whereas
      the glutathione concentration was decreased in rats fed higher amounts of vitamin
      E. This study shows that increasing the vitamin E content of the diet enhances
      ciprofibrate-induced hepatocarcinogenesis, but the mechanism of this effect is
      unclear.

PMID- 1975255
TI  - The contribution of epidemiology to cancer prevention and therapy. A report on a
      symposium, organized in Vienna by the International Agency for Research on Cancer
      and the Austrian Institute for Tumorbiology-Cancer Research, 7-9 March 1990.

PMID- 1975256
TI  - Workshop of the Umweltbundesamt on Environmental chemical risk factors of cancer:
      mechanisms of action and assay systems for detection, Berlin, 23-24 November
      1989.

PMID- 1975257
TI  - Transforming growth factor type beta 1 modulates the effects of basic fibroblast
      growth factor on growth and phenotypic expression of rat astroblasts in vitro.
AB  - In a search of the growth factors possibly involved in brain ontogenesis we have
      examined the effects of transforming growth factor beta 1 (TGF-beta 1) on the
      growth and phenotypic expression of rat astroblasts in primary culture. Along TGF
      beta 1 elicited only a slight negative effect on the growth of these cells.
      However, this factor was found to modulate the mitogenic effects of other growth
      factors. On quiescent cells it potentiates the mitogenic effect of basic
      fibroblast growth factor (bFGF) but not that of other growth factors, namely,
      epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and
      thrombin. TGF-beta 1 did not modulate significantly the stimulatory effect of
      these growth factors on the activity of the enzyme glutamine synthetase (GS); but
      kinetic studies showed that TGF-beta 1 delays the stimulation of GS activity. DNA
      synthesis monitored by the incorporation of [125I]iododeoxyuridine (125I-dUrd)
      was maximum after 24-30 h of treatment with bFGF. With bFGF plus TGF-beta 1 the
      maximum was shifted to 30-36 h. This shift is compatible with the idea that TGF
      beta 1 induces responsiveness in some cells which are otherwise unresponsive to
      the mitogenic action of bFGF, and that this induction requires some time. This
      hypothesis is sustained by the observation that in cells treated for only 12 h
      with bFGF, the treatment with TGF-beta 1 for the same 12 h or for longer time did
      not stimulate significantly the cell growth. Stimulation occurred only when the
      bFGF treatment was continued after 12 h. Potentiation of the mitogenic effect of
      bFGF and shift of the maximum 125I-dUrd incorporation towards 24 h was seen with
      cells pretreated with TGF-beta 1. This potentiation effect decreased with
      increasing time between the two treatments. The potentiation effect of TGF-beta 1
      is not mediated by an induction of new bFGF membrane receptors as seen by binding
      studies.

PMID- 1975258
TI  - Prevention by silymarin of membrane alterations in acute CCl4 liver damage.
AB  - The effect of silymarin on liver lipid peroxidation and membrane lipid
      alterations induced by an acute dose of CCl4 was studied. Four groups of animals
      were treated with CCl4, CCl4 + silymarin, silymarin and its vehicles. CCl4 was
      given orally (0.4 g 100 g-1 body wt.) and silymarin was administered i.p. All
      animals were sacrificed 24 h after the treatments. Liver lipid peroxidation was
      measured and plasma membranes were isolated. Alkaline phosphatase (AP) and gamma
      glutamyl transpeptidase (GGTP) were measured in plasma membranes. Membrane lipids
      were extracted and then analysed by thin-layer chromatography by measuring the
      phosphorus of the phospholipids in each spot. Liver lipid peroxidation was
      increased about three times in the group receiving CCl4 only. Silymarin
      cotreatment prevented this increase. Phosphatidylethanolamine (PEA) decreased,
      while phosphatidylinositol (PI) increased in the plasma membranes isolated from
      the CCl4-treated group. Animals that received CCl4 + silymarin showed no decrease
      in PEA content. A partial prevention of the decrease in phosphatidylinositol
      content was also observed in plasma membranes of animals treated with silymarin
      in addition to CCl4. CCl4 decreased gamma-glutamyl transpeptidase (GGTP) and
      alkaline phosphatase (AP) membrane activities. Silymarin cotreatment prevented
      the AP (completely) and the GGTP (partially) falls caused by CCl4. Silymarin by
      itself increased AP membrane activity. A significant relationship between the
      membrane content of phosphatidylethanolamine (PEA) and the AP activity was
      observed in plasma membranes of treated animals and in normal liver membranes
      enriched with PEA. These results indicate that silymarin can protect against the
      alterations induced by CCl4 on the liver plasma membrane through its antioxidant
      properties by modifying the plasma membrane phospholipid content.

PMID- 1975259
TI  - Human T cell activation. Synergy between CD73 (ecto-5'-nucleotidase) and signals
      delivered through CD3 and CD2 molecules.
AB  - Interaction of the glycosyl phosphatidylinositol-linked differentiation Ag CD73
      (ecto-5'-nucleotidase) with the CD73-specific mAb 1E9 generates agonistic signals
      that strongly synergize with T cell activation induced by CD3 and CD2 mAb. This
      synergy is observed only when 1E9 is immobilized on plastic and occurs in the
      absence of accessory cells or exogenous lymphokines. 1E9 induces a rapid (though
      transient) increase in [Ca2+]i in a minor proportion (20 to 30%) of
      unfractionated T lymphocytes (presumably CD73+ cells). However, this [Ca2+]i
      mobilization is not sufficient to fully activate CD73+ T cells, as shown by the
      requirement of additional signals such as CD3 or CD2 stimulation to initiate T
      cell proliferation. These signals cannot be substituted by the exogenous
      lymphokines, rIL-1, rIL-2, or rIL-4, or PMA (when T cells are rigorously depleted
      of monocytes). These data indicate that CD73 may behave as an accessory molecule
      regulating interactions between T cells and antigens or APC. A comparison was
      carried out with mAb 9.3 to the differentiation Ag CD28, another agonistic
      molecule with activating properties similar to CD73. Despite their lower
      percentage, the ability of CD73+ T cells to amplify the proliferation induced by
      CD3 or CD2 mAb was equivalent or even greater than that of CD28+ T cells. Once
      activated, CD73+ cells may recruit the remaining (CD73-) cells primed by CD3 or
      CD2 stimulation. Based on these data, we suggest that CD73+ T lymphocytes may be
      a specialized subset to amplify immune responses originated by the CD3 and CD2
      activation pathways. Finally, the functional association between CD73 and
      integral membrane molecules like CD3 and CD2 suggests that GPI-anchored molecules
      may play a role in transmembrane signaling mediated by conventional second
      messenger systems.

PMID- 1975260
TI  - A novel approach to the generation of high affinity class II-binding peptides.
AB  - We have found that if core regions crucial for class II binding are incorporated
      in multiple copies in the same peptide molecule ("reiterative motifs"), marked
      enhancement of the binding capacity occurs. Isotype specificity (IAd vs IEd
      binding capacities) is retained in all three antigenic determinants so far
      analyzed (lambda rep 12-26, OVA 323-339, and hen egg lysozyme 105-120). The
      mechanism involved in such an effect is not clear, but experiments involving
      introduction of a peptide spacer between two repeated core regions do not support
      the notion that the effect is mediated by cross-linking of more than one MHC
      molecule, favoring the possibility that conformational effects or distinct
      subsites of interaction on the MHC molecule may be involved. Based on reiterative
      structures, a peptide molecule composed of only two different amino acids (Ala
      and His) has been produced that still retains a very high binding affinity. An
      125I-radiolabeled form of this peptide has been used to demonstrate that the high
      binding detected is mediated by the same binding site involved in the interaction
      of IAd and OVA 323-339. Inhibition of Ag presentation studies further supports
      the immunologic relevance of the phenomena observed. Finally, we observed
      naturally occurring clustered binding sites in proximity of immunodominant
      protein regions, raising the possibility that the phenomenon might have a
      physiologic counterpart.

PMID- 1975261
TI  - Neutrophil adherence receptors (CD 18) in ischemia. Dissociation between
      quantitative cell surface expression and diapedesis mediated by leukotriene B4.
AB  - Neutrophils and eicosanoid chemoattractants are centrally involved with ischemia
      reperfusion (I/R) injury. The CD 18 complex of adhesive glycoproteins, readily up
      regulated by chemoattractants in vitro, is required for polymorphonuclear
      leukocyte (PMN) adherence to endothelium. This study tests whether CD 18 is up
      regulated by ischemia in vivo and its role in mediating PMN diapedesis.
      Anesthetized rabbits underwent 3 h of bilateral hindlimb tourniquet ischemia (n =
      16). Ten min after tourniquet release, levels of plasma leukotriene (LT)B4
      increased to 390 +/- 62 pg/ml (mean +/- SE), higher than 134 +/- 26 pg/ml in
      control rabbits (n = 13, p less than 0.01). Aliquots of plasma were added to
      whole blood from normal rabbits (n = 6) for flow cytometric analysis of
      neutrophils with the CD 18 mAb R 15.7. Addition of I/R plasma failed to
      demonstrate an increase in surface expression of CD 18. Similarly, no CD 18 up
      regulation was observed in vivo upon reperfusion in ischemic animals pretreated
      with mAb R 15.7 (n = 3). However, I/R plasma when introduced into plastic
      chambers taped atop dermabrasion sites in normal rabbits (n = 12) resulted in
      diapedesis, measured by the accumulation after 3 h of 1130 +/- 125 PMN/mm3 in the
      chambers relative to 120 +/- 31 PMN/mm3 with control plasma (p less than 0.01).
      Diapedesis in response to I/R plasma was abolished by pretreatment with mAb R
      15.7 (less than 5 PMN/mm3, n = 6), was reduced by U 75,302, an LTB4 receptor
      antagonist (253 +/- 101 PMN/mm3, n = 6) (both p less than 0.01) and was not
      protein synthesis dependent. These results demonstrate that PMN diapedesis in
      response to I/R plasma is exclusively dependent upon the CD 18 glycoprotein
      complex by an LTB4-dependent mechanism, despite the fact that CD 18 is not up
      regulated on circulating PMN in ischemia. These data indirectly indicate the
      functional importance of conformational changes of CD 18 in determining PMN
      adhesion.

PMID- 1975263
TI  - ELISA for quantitation of the extracellular domain of p185HER2 in biological
      fluids.
AB  - The HER2/neu proto-oncogene encodes a receptor that belong to the tyrosine
      specific protein kinase family. Amplification of the HER2 gene in patients with
      breast and ovarian cancer has been shown to predict poorer survival rates. In
      order to understand the role of HER2 in malignant and normal cells, it is
      necessary to devise assays that can quantitate expression levels of the HER2 gene
      product (p185HER2) in production samples, biopsy specimens and biological fluids.
      We have developed a simple, quantitative ELISA that uses two monoclonal
      antibodies directed against the extracellular domain of the HER2 gene product,
      p185HER2 (HER2 ECD). The assay has a detection range of 0.25-120 ng/ml, is
      precise and sensitive. The ability of this assay to detect biologically active
      rHER2 ECD is demonstrated by its correlation to a growth inhibitory bioassay (r =
      0.92). The sandwich ELISA can also accurately quantitate rHER2 ECD in mouse and
      monkey serum. This assay should be useful for quantitating low levels of
      circulating rHER2 ECD in animals in which rHER2 ECD is being used as antigen for
      immunotherapy and in patients which 'shed' receptor.

PMID- 1975262
TI  - Induction of murine lymphokine-activated killer cells by recombinant IL-7.
AB  - The data demonstrate that IL-7, a cytokine that was originally identified,
      purified, and cloned based upon its ability to support the growth of pre-B cells
      in vitro, also induces proliferation and promotes the generation of lymphokine
      activated killer (LAK) cell activity in populations of resting peripheral
      lymphoid cells. Although the kinetics of LAK induction by IL-7 (which peaked at
      days 6 to 8 of culture) was slower than that detected in cultures containing IL-2
      (which peaked at day 4), IL-7 was significantly more effective at maintaining
      cytotoxic activity over longer periods of time, and greater viable cell
      recoveries, than was IL-2. A wide range of murine tumor target cells were found
      to be lysed in an MHC-unrestricted fashion by IL-7 induced LAK, but syngeneic Con
      A-induced lymphoblasts were not; nor were target cells from the human tumors K562
      or Daudi lysed by IL-7 LAK. IL-7 LAK were induced in populations of lymphoid
      cells obtained from secondary lymphoid tissues (peripheral lymph nodes and
      spleen), but not from primary lymphoid tissues (thymus and bone marrow). LAK
      induced by IL-7 from unfractionated populations of lymphoid cells were completely
      eliminated by treatment with anti-CD8 or anti-Thy-1+C, and unaffected by
      treatment with anti-CD4, anti-asialo GM1 or anti-NK1.1+C. Interestingly, although
      no detectable CD4+ effector cells could be detected in populations of LAK
      generated from unfractionated populations of lymphoid cells stimulated by IL-7,
      they were found to be generated from populations of lymphoid cells from which
      CD8+ cells had been eliminated before being cultured in medium containing IL-7.
      These data suggest that CD4+ T cells do not normally give rise to IL-7-induced
      LAK unless they are first separated from CD8+ T cells. LAK induced by IL-7 appear
      to be distinct from LAK activity induced by IL-2 in that there is no detectable
      involvement of NK-like effector cells at either the precursor or effector cell
      stages.

PMID- 1975264
TI  - Fc gamma RII-mediated superoxide production by phagocytes is augmented by GM-CSF
      without a change in Fc gamma RII expression.
AB  - Freshly purified neutrophils and monocytes respond to multiple cross-linking of
      Fc gamma RII with the IgG1 monoclonal antibody, CIKM5, with a rapid rise in
      Ca(2+)i, but not with a respiratory burst, although superoxide is generated by
      these cells when stimulated with the chemotactic peptide, FMLP, or phorbol ester
      (TPA). Incubation in vitro for 30-60 min at 37 degrees C in medium + 0.1% FCS had
      no effect on the neutrophil superoxide response to CIKM5 but induced a weak
      monocyte response in 11/13 experiments. However, incubation with rhGM-CSF (10
      ng/ml) under similar conditions induced a neutrophil respiratory burst in
      response to cross-linking Fc gamma RII in 12/14 experiments and enhanced the
      monocyte response by 181%. GM-CSF also enhanced the response of neutrophils and
      monocytes to FMLP by 308% and 165%, respectively. The response to TPA was not
      significantly enhanced by GM-CSF. rhIFN-gamma (100 mu/ml) was ineffective as a
      priming agent for all agonists tested in short-term incubations but augmented the
      monocyte response to CIKM5 after 5 d exposure in vitro. Whilst GM-CSF induced
      neutrophil superoxide production in response to cross-linking Fc gamma RII, there
      was no concomitant change in Fc gamma RII expression either in in vitro studies
      of neutrophils from healthy individuals or in in vivo studies of patients
      receiving GM-CSF. Stimulation of unprimed neutrophils with CIKM5 induced a rapid
      transient increase in intracellular calcium levels to 181% of resting levels.
      However, incubation with GM-CSF did not further augment the calcium transients
      above the stimulated level. The mechanism by which GM-CSF induces an enhanced
      respiratory burst in response to cross-linking of Fc gamma RII remains to be
      elucidated, but is not related to receptor expression or increases in receptor
      mediated calcium mobilization.

PMID- 1975265
TI  - Physiology of Saccharomyces cerevisiae in anaerobic glucose-limited chemostat
      cultures.
AB  - The physiology of Saccharomyces cerevisiae CBS 8066 was studied in anaerobic
      glucose-limited chemostat cultures in a mineral medium supplemented with
      ergosterol and Tween 80. The organism had a mu max of 0.31 h-1 and a Ks for
      glucose of 0.55 mM. At a dilution rate of 0.10 h-1, a maximal yield of 0.10 g
      biomass (g glucose)-1 was observed. The yield steadily declined with increasing
      dilution rates, so a maintenance coefficient for anaerobic growth could not be
      estimated At a dilution rate of 0.10 h-1, the yield of the S. cerevisiae strain
      H1022 was considerably higher than for CBS 8066, despite a similar cell
      composition. The major difference between the two yeast strains was that S.
      cerevisiae H1022 did not produce acetate, suggesting that the observed difference
      in cell yield may be ascribed to an uncoupling effect of acetic acid. The absence
      of acetate formation in H1022 correlated with a relatively high level of acetyl
      CoA synthetase. The uncoupling effect of weak acids on anaerobic growth was
      confirmed in experiments in which a weak acid (acetate or propionate) was added
      to the medium feed. This resulted in a reduction in yield and an increase in
      specific ethanol production. Both yeasts required approximately 35 mg oleic acid
      (g biomass)-1 for optimal growth. Lower or higher concentrations of this fatty
      acid, supplied as Tween 80, resulted in uncoupling of dissimilatory and
      assimilatory processes.

PMID- 1975266
TI  - Neuropeptide levels in Alzheimer's disease and dementia with frontotemporal
      degeneration.
AB  - The CSF levels of somatostatin-LI (SLI), neuropeptide Y (NPY-LI) and Delta Sleep
      Inducing Peptide (DSIP-LI) have been measured in patients with dementia of
      Alzheimer type (DAT) and dementia with frontotemporal degeneration of non
      Alzheimer type (FTD). The distribution pattern of cortical degeneration differs
      between these two types of dementia. DAT shows degeneration of mainly temporo
      parietal and temporo-limbic structures, whereas FTD discloses its main
      degeneration in the frontotemporal regions (Brun, 1987). The somatostatin-LI was
      significantly reduced both in DAT and FTD. NPY-LI showed a significant reduction
      in DAT but not in FTD. A tendency to a reduction with duration of the disease was
      observed in DAT whereas the contrary was noted in FTD. The DSIP-LI levels were
      reduced in DAT and slightly increased in FTD. The study provides an evidence of
      neurochemical differences between the two primary degenerative dementias.

PMID- 1975267
TI  - (+)-PHNO: a new anti-parkinsonian agent which does not induce chorea in MPTP
      treated squirrel monkeys.

PMID- 1975268
TI  - Myasthenia gravis and thymoma in multiple endocrine neoplasia (MEN-1) syndrome.

PMID- 1975269
TI  - Acute neuropathological changes in the caudate nucleus caused by MPTP and
      methamphetamine: immunohistochemical studies.
AB  - Three days after the administration of MPTP (1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine) or methamphetamine to mice, there is degeneration and
      disappearance of punctate tyrosine hydroxylase-containing synaptic endings in the
      caudate nucleus. The neuropil is occupied with longer, varicose, branching
      fibres, which appear to be preterminal fibres. An intense gliosis occurs. The
      sparsely-occurring glial cells, with profuse lightly-stained (by glial fibrillary
      acidic protein) processes which are primarily located near blood vessels, become
      transformed into more heavily-stained star-shaped cells with fewer but thicker
      processes. These cells are distributed throughout the caudate. Despite apparent
      differences in the mechanism by which MPTP and methamphetamine cause dopamine
      depletion, the neuropathological changes in the caudate induced by these
      substances are identical.

PMID- 1975270
TI  - Do neuroleptic drugs still have a place in neurological therapy?

PMID- 1975271
TI  - Early dermato-pathological signs during bath-PUVA therapy.
AB  - The combination of trioxsalen bath and long-wave UV-A is used in dermatology to
      treat selected patients with psoriasis. Such treatment induces side effects whose
      clinical aspects have already been described. We report the histological aspects
      of these lesions. The most striking features occur in the epidermis, where we
      found vacuolar alterations, disorganization of the stratum malpighi, necrotic
      cells, and Bowenoid changes. Langerhans cells are reduced in number, and
      melanocytes may become large and atypical. In addition, factor XIIIa-positive
      dendrocytes of the superficial dermis increase in size, and some of them migrate
      into the epidermis, which is a rare location for these cells.

PMID- 1975273
TI  - Correctly positioned and soldered wrought wire clasps for removable partial
      dentures.

PMID- 1975272
TI  - Allosteric potentiation of quisqualate receptors by a nootropic drug aniracetam.
AB  - 1. Allosteric potentiation of the ionotropic quisqualate (iQA) receptor by a
      nootropic drug aniracetam (1-p-anisoyl-2-pyrrolidinone) was investigated using
      Xenopus oocytes injected with rat brain mRNA and rat hippocampal slices. 2.
      Aniracetam potentiates the iQA responses induced in Xenopus oocytes by rat brain
      mRNA in a reversible manner. This effect was observed above the concentrations of
      0.1 mM. Kainate. N-methyl-D-aspartate and gamma-aminobutyric acid responses
      induced in the same oocytes were not affected. 3. The specific potentiation of
      iQA responses was accompanied by an increase in the conductance change of iQA and
      alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) responses, but
      the affinity of receptors for agonist and the ion-selectivity of the channels
      (reversal potentials) were not changed. 4. Aniracetam reversibly potentiated the
      iQA responses recorded intracellularly from the pyramidal cells in the CA1 region
      of rat hippocampal slices. The excitatory postsynaptic potentials (EPSPs) in
      Schaffer collateral-commissural-CA1 synapses were also potentiated by aniracetam.
      5. Population EPSPs recorded in the mossy fibre-CA3 synapses as well as Schaffer
      commissural synapses were also potentiated by aniracetam. The amplitudes of the
      potentiation were not changed by the formation of long-term potentiation.

PMID- 1975274
TI  - Synthesis and dopamine receptor affinities of 2-(4-fluoro-3-
      hydroxyphenyl)ethylamine and N-substituted derivatives.
AB  - The synthesis of 2-(4-fluoro-3-hydroxyphenyl)ethylamine (26) and of some N,N
      dialkyl derivatives (27-30) starting from 4-fluoro-3-hydroxytoluene and their in
      vitro binding affinities for dopamine (DA) receptor are reported. The amine 26
      can be regarded as a molecular modification of DA in which the para hydroxyl
      group is replaced by fluorine. The new compounds 26-30 were evaluated for their
      affinity at D-1 and D-2 DA receptor subtypes by displacement of [3H]SCH 23390 (D
      1 selective) and [3H]spiperone (D-2 selective). The amine 26 had about 2-fold
      less affinity for D-1 and D-2 binding sites than DA. The substitution of the
      amino group with ethyl, n-propyl, and 2-phenylethyl groups decreased the affinity
      for D-1 binding sites but greatly enhanced the effectiveness on D-2 binding
      sites. The N-ethyl- (28) and N-n-propyl-N-(2-phenylethyl)-2-(4-fluoro-3-
      hydroxyphenyl)ethylamine (30) were the most potent members of the series with
      high selectivity for D-2 binding sites. A similar effect was observed with
      isomeric N-n-propyl-N-(2-phenylethyl)-2-(3-fluoro-4-hydroxyphenyl)ethylamine (31)
      which was approximately 65 times more selective for D-2 sites vs D-1 sites. The
      introduction of a 2-phenylethyl group on the nitrogen atom induce the highest
      effect, perhaps as a consequence of an increased liposolubility or of binding to
      a complementary lipophilic site on the receptor.

PMID- 1975275
TI  - Synthesis and structure-activity relationships of N,N'-di-o-tolylguanidine
      analogues, high-affinity ligands for the haloperidol-sensitive sigma receptor.
AB  - With an eye toward the development of novel atypical antipsychotic agents, we
      have studied the structure-affinity relationships of N,N'-di-o-tolylguanidine
      (DTG, 3) and its congeners at the haloperidol-sensitive sigma receptor. A number
      of DTG analogues were synthesized and evaluated in in vitro radioligand
      displacement experiments with guinea pig brain membrane homogenates, using the
      highly sigma-specific radioligands [3H]-3 and [3H]-(+)-3-(3-hydroxyphenyl)-N-(1
      propyl)piperidine and the phencyclidine (PCP) receptor specific compounds [3H]-N
      [1-(2-thienyl)-cyclohexyl]piperidine and [3H]-(+)-5-methyl-10,11-dihydro-5H
      dibenzo[a,d]cyclohepten-5,10- imine. The affinity of N,N'-diarylguanidines for
      the sigma receptor decreases with increasing steric bulk of ortho substituents
      larger than C2H5. Hydrophobic substituents are generally preferred over similarly
      positioned hydrophilic ones. Furthermore, electroneutral substituents are
      preferred over strongly electron donating or withdrawing groups. Significant
      binding to the sigma receptor is usually retained as long as at least one side of
      the guanidine bears a preferred group (e.g. 2-CH3C6H5). Replacement of one or
      both aryl rings with certain saturated carbocycles (e.g. cyclohexyl, norbornyl,
      or adamantyl) leads to a significant increase in affinity. By combining the best
      aromatic and best saturated carbocyclic substituents in the same molecule, we
      arrived at some of the most potent sigma ligands described to date (e.g. N-exo-2
      norbornyl-N'-(2-iodophenyl)guanidine, IC50 = 3 nM vs [3H]-3). All of the
      compounds tested were several orders of magnitude more potent at the sigma
      receptor than at the PCP receptor, with a few notable exceptions. This series of
      disubstituted guanidines may be of value in the development of potential
      antipsychotics and in the further pharmacological and biochemical
      characterization of the sigma receptor.

PMID- 1975276
TI  - Synthesis and evaluation of a series of aryl[e]fused pyrazolo[4,3-c]pyridines
      with potential anxiolytic activity.
AB  - A series of pyrazolo[4,3-c]pyridines has been synthesized and evaluated as
      potential anxiolytic agents. Selected compounds from this series show a
      pharmacological profile of action different from that of diazepam. A number of
      the compounds possess higher affinity for central benzodiazepine receptors than
      diazepam, yet show less anticonvulsant activity and are less sedative. The
      structure-activity relationships of these potential anxiolytic agents are
      discussed.

PMID- 1975277
TI  - Treatment of acute duodenal ulcers with famotidine and its comparison with other
      H2 blockers.
AB  - Famotidine, a new H2 antagonist in a dose of 40 mg qhs was tried in a clinical
      trial for the treatment of duodenal ulcer in 25 patients and compared with other
      H2 antagonists. Cimetidine 800 mg qhs and Ranitidine 300 mg qhs were used in a
      similar number of randomised patients. Patients were evaluated clinically,
      biochemically and endoscopically. At the end of eight weeks, the healing rate
      with Famotidine was 96%. Cimetidine was 92% and Ranitidine 96%. No significant
      side effects were noted with any of these drugs. In conclusion, Famotidine (40 mg
      qhs) is an effective and generally well-tolerated drug in the treatment of acute
      duodenal ulcer.

PMID- 1975278
TI  - Pharmacological actions of SM-9018, a new neuroleptic drug with both potent 5
      hydroxytryptamine2 and dopamine2 antagonistic actions.
AB  - Pharmacological studies were undertaken to clarify the profile of cis-2-(4-(4
      (1,2-benzisothiazol-3-yl)-1-piperazinyl) butyl) hexahydro-1H-isoindole-1,3-(2H)
      dione hydrochloride (SM-9018), a new neuroleptic drug. SM-9018 had very high
      binding affinities for both 5-hydroxytryptamine2 (5-HT2) and dopamine2 (D2)
      receptors, unlike many other neuroleptics. SM-9018 also strongly inhibited 5-HT2
      receptor-mediated behavior such as tryptamine-induced clonic seizure and D2
      receptor-mediated behavior such as methamphetamine-induced hyperactivity,
      apomorphine-induced stereotypy and climbing behavior. SM-9018 possessed only a
      weak cataleptogenic activity, which may be clinically related to extrapyramidal
      side effects, despite its potent D2 antagonistic activity. Moreover, SM-9018
      induced weak central depressant effects such as inhibition of spontaneous
      locomotor activity and motor coordination, as compared with classical
      neuroleptics (haloperidol and chlorpromazine). These results suggest that SM-9018
      is a new neuroleptic drug with both potent 5-HT2 and D2 antagonistic activities
      and with low cataleptogenic and central depressant activities.

PMID- 1975279
TI  - Effect of minaprine and other reference drugs on passive avoidance impairment
      induced by cerebral ischemia in Mongolian gerbils.
AB  - We examined the characteristics of cerebral ischemia-induced behavioral deficit
      in the passive avoidance task and the effect of minaprine and other
      cytoprotective drugs on passive avoidance deficit induced by cerebral ischemia in
      Mongolian gerbils. Severe impairment of passive avoidance was apparent when the
      duration of the ischemia exceeded 2 min. Histopathological ischemic neuronal
      damage in CA1 neurons at 7 days after occlusion was also induced when the
      ischemia was over 2 min. Otherwise, although cerebral ischemia was carried out at
      5 min, 2 hr, 5 hr or 24 hr after the training session, the passive avoidance
      deficit was produced 24 hr after the training session. When the training session
      was carried out 24 hr before the occlusion, minaprine, which was administered 30
      min before the occlusion, led to a recovery of the response latency.
      Pentobarbital, diazepam and ethylapovincamine improved the passive avoidance
      deficit induced by 5-min bilateral carotid artery occlusion. On the other hand,
      the passive avoidance deficit was not ameliorated by Ca(++)-hopantenate,
      nicardipine and idebenone. The hippocampal damage at 7 days after occlusion was
      prevented by the drugs that ameliorated the passive avoidance deficit. The
      relationship between passive avoidance deficit and CA1 neuronal death in the
      hippocampus induced by cerebral ischemia warrants further attention.

PMID- 1975280
TI  - [Current concepts concerning the pathogenesis, prognostication and treatment of
      paroxysmal forms of fibrillation arrhythmia].

PMID- 1975281
TI  - [Beta-adrenergic reactivity in patients with myocardial infarct according to the
      antihemolytic test].
AB  - Propranolol antihemolytic test parameters calculated with the Hill mathematical
      model from dose-dependent curves of saturation were studied in 27 patients with
      myocardial infarction. Erythrocyte beta-adrenoreceptors showed higher sensitivity
      to propranolol in patients with myocardial infarction within 3 days of the
      disease. Three weeks after therapy, changes were found in the erythrocyte
      membranes solely in patients receiving beta-adrenoblockers. The changes are
      indicative of lower sensitivity of beta-adrenoreceptors to the beta-blocker.
      Persons with varying responses to propranolol were detected among the patients
      with myocardial infarction, which may be used to define indications for beta
      adrenoblocker therapy.

PMID- 1975282
TI  - [A rare case of acute abdomen in an hermaphrodite].

PMID- 1975284
TI  - [Evidence of HTLV-I infection in different risk groups in Barcelona].

PMID- 1975283
TI  - Assessment of local cellular immunity in lung cancer by bronchoalveolar lavage.
AB  - Small cell lung cancer (SCLC) is the most malignant of the pulmonary neoplasms
      and is associated with a poor local cellular immune response. 16 patients with
      non small cell lung cancer (NSCLC) and 11 patients with SCLC underwent
      bronchoalveolar lavage (BAL) in the lung which harbored the tumor in order to
      investigate the lymphocyte surface antigens utilizing the immunoperoxidase
      technique. Analysis of blood lymphocytes was performed in parallel. 8 patients
      with previous sarcoidosis in complete remission who underwent BAL and 10 normal
      blood donors served as controls. Among blood lymphocytes the CD3+, CD4+ and CD16+
      cell populations were elevated significantly and the T4/T8 ratio was elevated in
      NSCLC patients, but only CD16+ were augmented in SCLC. Cell populations
      expressing the activation markers transferrin (TF) receptor, interleukin-2 (IL-2)
      receptor and the very late antigen VAL-1 were also increased in NSCLC, while SCLC
      was associated with antigen distributions similar to controls. No differences
      between the cohorts were seen in the expression of human leukocyte antigen (HLA)
      DR. In BAL the population of CD3+ and CD4+ cells were reduced in SCLC and the
      T4/T8 ratio was diminished in contrast to controls and NSCLC patients, whereas
      these two latter groups did not differ from each other. The distribution pattern
      of CD16, TF receptor and IL-2 receptor in the study groups resembled that of
      cells of the blood stream, but CD16+ natural killer cells were additionally down
      regulated to control values in SCLC. No differences were seen in the distribution
      of VLA-1. HLA-DR+ cells were clearly elevated in both cancer groups.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1975285
TI  - Effect of a new computed tomographic image transfer system on management of
      referrals to a regional neurosurgical service.
AB  - A computed tomographic image transfer system ('Image Link') was used to link
      scanners within the Oxford region, UK, to the regional neurosurgical service. 100
      consecutive neurosurgical referrals were examined by this system; 43% of the
      emergency referrals did not require transfer, 31% were transferred electively,
      and 26% urgently. Most of the patients defined as potentially hazardous for
      transfer (10/11) did not require neurosurgical intervention. The delay by the use
      of the system was negligible and early detection of intracranial haematoma
      contributed to good outcome in some head injured patients. Overall, 3,170 miles
      of ambulance journey were avoided. Use of image link has led to substantial
      improvements in management of neurosurgical emergency referrals, cost
      effectiveness of neurosurgical and ambulance facilities, and interhospital
      communication between doctors.

PMID- 1975286
TI  - Risk of neural tube defects in relation to maternal fertility and fertility drug
      use.
AB  - In a case-control study to investigate whether women who use drugs to induce
      ovulation are at increased risk of conception of a child with a neural tube
      defect, 571 women who had a fetus or child with a neural tube defect, 546 women
      who had a fetus or child with other abnormalities, and 573 women who had an
      apparently normal fetus or child were questioned about infertility, fertility
      drug use, and related obstetric problems. The rate of maternal fertility drug use
      around the time of conception was not significantly higher for neural tube
      defects than for other abnormalities (odds ratio 1.28; 95% confidence interval
      0.39, 4.51) or no abnormalities (odds ratio 0.80; 95% Cl 0.27, 2.27). Fertility
      drug use at any time was not significantly more frequent for neural tube defects
      than for other abnormalities (odds ratio 1.37; 95% Cl 0.70, 2.74) or no
      abnormalities (odds ratio 1.05; 95% Cl 0.56, 1.98).

PMID- 1975287
TI  - Religious beliefs and parental duty.

PMID- 1975288
TI  - Pancreas transplantation or insulin?

PMID- 1975289
TI  - Small-bowel transplantation: European experience.

PMID- 1975291
TI  - Babesiosis, asplenia, and AIDS.

PMID- 1975292
TI  - Genital ulcers and HIV antibody.

PMID- 1975290
TI  - Treatment of malaria with sulfadoxine/pyrimethamine: note of caution.

PMID- 1975293
TI  - Xenon in anaesthesia.

PMID- 1975294
TI  - Dangers of nebulisers in nursing and residential homes.

PMID- 1975295
TI  - Obstacle to early diagnosis of herpes simplex encephalitis via CSF.

PMID- 1975296
TI  - Blackfoot disease: arsenic or humic acid?

PMID- 1975297
TI  - Potassium and sudden unexplained nocturnal death.

PMID- 1975298
TI  - Dangers of dietary germanium supplements.

PMID- 1975299
TI  - Acquired C1 esterase inhibitor deficiency as manifestation of T-cell
      lymphoproliferative disorder.

PMID- 1975300
TI  - Unusual diagnosis of phaeochromocytoma.

PMID- 1975301
TI  - Difficulties with controlled release prostaglandin E2 pessaries.

PMID- 1975302
TI  - Consensus conferences.

PMID- 1975303
TI  - Genetics, ethics, and audit.

PMID- 1975304
TI  - Insane automatism.

PMID- 1975305
TI  - Litigation and criticisms about drugs.

PMID- 1975306
TI  - Tryptophan-associated eosinophilia-myalgia syndrome and pancreatitis.

PMID- 1975307
TI  - Intrauterine blood transfusion for non-immune hydrops fetalis due to parvovirus
      B19 infection.

PMID- 1975308
TI  - Obstetric complications and schizophrenia.

PMID- 1975309
TI  - Antibody to hepatitis C virus in Hungary. The Hungarian Multicenter HCV Study
      Group.

PMID- 1975310
TI  - Self-induced "buzz" achieved by rapid infusion of immunoglobulin.

PMID- 1975311
TI  - Potency of high purity factor VIII concentrates.

PMID- 1975312
TI  - Successful mifepristone treatment of recurrent, inoperable meningioma.

PMID- 1975313
TI  - Quinolone resistance in Salmonella spp: veterinary pointers.

PMID- 1975314
TI  - Borrelia burgdorferi ELISA titres in children with recent mumps meningitis.

PMID- 1975315
TI  - Immunity to poliomyelitis.

PMID- 1975316
TI  - Activated eosinophils in chronic inflammatory bowel disease.

PMID- 1975317
TI  - Response to doxorubicin/methotrexate/fluorouracil in advanced adenocarcinoma of
      pancreas or biliary tract.

PMID- 1975318
TI  - Cerebral metastasis presenting as migraine with aura.

PMID- 1975319
TI  - Albumin and serum proteins.

PMID- 1975320
TI  - Garin-Bujadoux-Bannwarth syndrome.

PMID- 1975321
TI  - GISSI-2: a factorial randomised trial of alteplase versus streptokinase and
      heparin versus no heparin among 12,490 patients with acute myocardial infarction.
      Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico.
AB  - A multicentre, randomised, open trial with a 2 x 2 factorial design was conducted
      to compare the benefits and risks of two thrombolytic agents, streptokinase (SK,
      1.5 MU infused intravenously over 30-60 min) and alteplase (tPA, 100 mg infused
      intravenously over 3 h) in patients with acute myocardial infarction admitted to
      coronary care units within 6 h from onset of symptoms. The patients were also
      randomised to receive heparin (12,500 U subcutaneously twice daily until
      discharge from hospital, starting 12 h after beginning the tPA or SK infusion) or
      usual therapy. All patients without specific contraindications were given
      atenolol (5-10 mg iv) and aspirin (300-325 mg a day). The end-point of the study
      was the combined estimate of death plus severe left ventricular damage. 12,490
      patients were randomised to four treatment groups (SK alone, SK plus heparin, tPA
      alone, tPA plus heparin). No specific differences between the two thrombolytic
      agents were detected as regards the combined end-point (tPA 23.1%; SK 22.5%;
      relative risk 1.04, 95% Cl 0.95-1.13), nor after the addition of heparin to the
      aspirin treatment (hep 22.7%, no hep 22.9%; RR 0.99, 95% Cl 0.91-1.08). The
      outcome of patients allocated to the four treatment groups was similar with
      respect to baseline risk factors such as age, Killip class, hours from onset of
      symptoms, and site and type of infarct. The rates of major in-hospital cardiac
      complications (reinfarction, post-infarction angina) were also similar. The
      incidence of major bleeds was significantly higher in SK and heparin treated
      patients (respectively, tPA 0.5%, SK 1.0%, RR 0.57, 95% Cl 0.38-0.85; hep 1.0%,
      no hep 0.6%, RR 1.64, 95% Cl 1.09-2.45), whereas the overall incidence of stroke
      was similar in all groups. SK and tPA appear equally effective and safe for use
      in routine conditions of care, in all infarct patients who have no
      contraindications, with or without post-thrombolytic heparin treatment. The 8.8%
      hospital mortality of the study population (compared with approximately 13% in
      the control cohort of the GISSI-1 trial) indicates the beneficial impact of the
      proven acute treatments for AMI.

PMID- 1975322
TI  - In-hospital mortality and clinical course of 20,891 patients with suspected acute
      myocardial infarction randomised between alteplase and streptokinase with or
      without heparin. The International Study Group.
AB  - In a study with 2 x 2 factorial design, 20,891 patients with suspected acute
      myocardial infarction of less than 6 h duration (12,490 from the GISSI-2 trial
      and 8401 recruited elsewhere) were randomly allocated to alteplase (recombinant
      tissue plasminogen activator, tPA) or streptokinase (SK) and to subcutaneous
      heparin, beginning 12 h after the start of thrombolytic therapy or no heparin.
      The protocol recommended that, in the absence of specific contraindications, all
      patients should receive aspirin and intravenous beta-blockade as soon as
      possible. No significant differences in hospital mortality were found between tPA
      and SK (8.9% versus 8.5%) or between heparin and no heparin (8.5% versus 8.9%).
      The incidence of major cardiac complications was also very similar in the
      different groups. For non-cardiac complications significant differences between
      the treatment groups were observed: more strokes were reported with tPA than with
      SK (1.3% versus 1%) while more major bleeds occurred with SK than with tPA (0.6%
      versus 0.9%). Subcutaneous heparin was likewise associated with an excess of
      major bleeds (1.0% with heparin versus 0.5% without heparin) but did not affect
      the incidence of stroke or reinfarction.

PMID- 1975323
TI  - Metabolic rate and physical development in children at risk of obesity.
AB  - Children of obese (group O) and normal-weight (group N) parents who took part in
      a study of metabolic rates and food intakes when 3-5 years old were restudied 12
      years later. There were striking differences between the sexes. Among the 15
      adolescent boys, parental obesity predicted more rapid growth (but not adiposity)
      and an earlier decline in resting metabolic rate (RMR)/kg body weight, and
      childhood energy intake/kg body weight was not predictive. Among the 10 girls,
      the opposite pattern was observed; childhood energy intake/kg predicted both body
      size and adiposity, and parental obesity had less predictive value. The sex
      differences are consistent with the earlier maturation of girls, and the growth
      differences with the hypothesis that a low RMR/kg body weight is associated with
      a precocious pattern of growth and development in children predisposed to
      obesity.

PMID- 1975324
TI  - Conservative treatment of ectopic pregnancy with local injection of hyperosmolar
      glucose solution or prostaglandin-F2 alpha: a prospective randomised study.
AB  - In a prospective randomised study, 31 patients with an unruptured tubal pregnancy
      were treated either with local and systemic prostaglandins or with local
      instillation of a hyperosmolar glucose solution. Prostaglandin therapy was
      successful in 13 of 15 patients and glucose therapy in 16 of 16. 9 women treated
      with prostaglandins had cramping abdominal pains postoperatively. No side-effects
      were noted in those treated with glucose. At subsequent hysterosalpingography 5
      of 6 patients treated with prostaglandins and 7 of 8 treated with glucose had
      normal tubal configuration and patency. 3 patients treated with glucose later had
      a normal intrauterine pregnancy, demonstrably through the affected tube in 1
      case. These results suggest that local instillation of hyperosmolar glucose
      solution is an option in the laparoscopic management of unruptured tubal
      pregnancies.

PMID- 1975325
TI  - "Endogenous" benzodiazepine activity in body fluids of patients with hepatic
      encephalopathy.
AB  - Body fluids from patients with hepatic encephalopathy and from controls with no
      renal or hepatic disease were assayed for benzodiazepine immunoreactivity and
      benzodiazepine-receptor-binding activity. The subjects had taken no synthetic
      benzodiazepines for at least 3 months. Benzodiazepine receptor binding in
      cerebrospinal fluid was significantly higher in hepatic encephalopathy patients
      than in controls (210 [SE 50.2] vs 40.7 [7.3] oxazepam equivalents [ng/ml]). The
      severity of hepatic encephalopathy was directly and significantly correlated with
      the level of benzodiazepine activity by radioreceptor assay or radioimmunoassay
      in urine and in plasma. Benzodiazepine activity equivalent to levels of more than
      900 ng/ml was found in patients with advanced encephalopathy. Although the
      chemical identity and source of this substance (or substances) are still unknown,
      its properties and the estimated levels of activity suggest it may have a role in
      the pathogenesis of the neural inhibition seen in hepatic encephalopathy.

PMID- 1975326
TI  - Is it a boy?

PMID- 1975327
TI  - Phrenic nerve pacing in quadriplegia.

PMID- 1975328
TI  - A new immunoassay.

PMID- 1975329
TI  - Cabbage syndrome.

PMID- 1975330
TI  - Juvenile and adult systemic-onset Still's disease.

PMID- 1975331
TI  - Epidemiology, classification, natural history, and genetics of epilepsy.

PMID- 1975332
TI  - Nosocomial Clostridium difficile colonisation and disease.
AB  - To assess the risk of acquiring Clostridium difficile diarrhoea or colitis in
      patients colonised with C difficile, rectal swabs taken weekly for 9 weeks from
      patients with long-term (at least 7 days) hospital stays on three wards were
      cultured for C difficile. 60 (21%) of 282 patients were culture-positive for C
      difficile during their hospital stay, of whom 51 were symptom-free faecal
      excretors. C difficile diarrhoea developed in the other 9 patients; 2 were
      culture-positive for C difficile and had diarrhoea at the time of first culture,
      and 7 had diarrhoea or pseudomembranous colitis after 1-6 previously negative
      weekly rectal cultures. All patients with diarrhoea were on one ward, but symptom
      free, excretors were found on all wards. HindIII chromosomal restriction
      endonuclease analysis (REA) of the C difficile isolates revealed 18 distinct
      types. All isolates from the patients with diarrhoea were one of two nearly
      identical REA types, B or B2. 26 of the 29 total B/B2 isolates were from patients
      on the same ward, which points to a nosocomial outbreak. The symptom-free
      excretors were not at increased risk of subsequent clinical illness.

PMID- 1975333
TI  - Comparison of reactogenicity and antigenicity of M37 rotavirus vaccine and rhesus
      rotavirus-based quadrivalent vaccine.
AB  - 90 Venezuelan infants aged 10-20 weeks were randomly allocated to four groups
      which received one of the following: the M37 vaccine (1 x 10(4) pfu [plaque
      forming units]); quadrivalent rotavirus vaccine (1 x 10(4) pfu each of serotype 3
      rhesus rotavirus [RRV] and human rotavirus-RRV reassortants of serotypes 1, 2,
      and 4); balanced quadrivalent vaccine consisting of 1 x 10(4) pfu of serotype 1
      and 3 components but 5 x 10(4) pfu of serotype 2 and 4 components; or placebo.
      The frequencies of transient febrile responses in these four groups were 20%,
      27%, 30%, and 9%. 50% of 22 infants tested who received M37 vaccine showed a
      serum rotavirus IgA antibody response, compared with 74% of the 23 quadrivalent
      and 86% of the 22 balanced-quadrivalent recipients. 64% of the M37 recipients
      showed a neutralising antibody response to M37; 27% showed such responses to
      human serotype 1 Wa strain and 27% to serotype 4 neonatal strain ST3. 17-39% of
      the quadrivalent recipients and 27-41% of the balanced-quadrivalent recipients
      showed neutralising antibody responses to serotypes 1-4. 70-73% of the
      quadrivalent and balanced quadrivalent groups also showed neutralising antibody
      responses to RRV.

PMID- 1975334
TI  - Attenuation of nocturnal asthma by cromakalim.
AB  - In a randomised, double-blind, crossover study, single oral doses of cromakalim,
      a potassium-channel activator, or placebo were given to 23 patients with
      nocturnal asthma. There was a significant reduction (p less than 0.005) in the
      early morning fall in forced expiratory volume in 1 s (FEV1) after 0.5 mg
      cromakalim (fall 9.8% [SEM 3.2%]) compared with placebo (18.5 [2.8]%). In a
      repeat dosing study, administration of 0.25 mg and 0.5 mg cromakalim on 5
      consecutive nights to a further group of 8 asthmatic subjects significantly
      reduced the early morning fall in FEV1 from 28.7 (6.5)% after placebo to 19
      (4.2)% after 0.25 mg and 14.9 (6.5)% after 0.5 mg. Potassium-channel activators
      may be useful in the treatment of asthma, especially for nocturnal symptoms.

PMID- 1975335
TI  - Interferon-induced enhancement of 2',5'-oligoadenylate synthetase in mid-gut
      carcinoid tumours.
AB  - Freshly explanted tumour cells from 22 patients with mid-gut carcinoid were used
      for in-vitro analysis of the capacity of recombinant interferon (rIFN) to induce
      the enzyme 2',5'-oligoadenylate synthetase (2',5'-A synthetase). 21 samples (95%)
      could be evaluated. IFN achieved a clinical response, by predetermined criteria,
      in 9 of the 21 patients (43%). There was a significant association between
      induction of 2',5'-A synthetase and clinical response: if the in-vitro
      intracellular concentrations of the enzyme increased by less than a factor of 3,
      remission did not occur (9 of 9; 100%), whereas remission was observed in 9 of 12
      patients (75%) in whom in-vitro intracellular 2',5'-A synthetase concentrations
      at least trebled. Anti-IFN antibodies developed in 6 of 12 patients treated with
      rIFN-alpha 2a but in 0 of 10 who received rIFN-alpha 2b. This in-vitro test may
      help to identify patients with carcinoid tumours who are unlikely to benefit from
      IFN therapy, so that other forms of treatment can be started early and the side
      effects of IFN are not suffered unnecessarily. Adaptations of this test may be
      possible for other tumours that may respond to treatment by IFN or similar
      compounds.

PMID- 1975336
TI  - Dilution of nebulised aerosols by air entrainment in children.
AB  - Guidelines for use of aerosolised drugs in children are inconsistent. In a study
      of 14 infants, 22 children, and 4 adults inspired nebulised aerosols were diluted
      more for large than for small subjects, because of air entrainment which occurred
      when inspiratory flow exceeded nebuliser flow. Infants under 6 months of age did
      not entrain air and would receive undiluted aerosols. All other subjects
      entrained air, which caused up to a 5-fold dilution in inspired aerosol
      concentration as subject size increased. In subjects who entrained air, the ratio
      of inspired nebuliser output versus total nebuliser output was relatively
      constant, and was related to the respiratory pattern. For a given nebuliser
      solution concentration, infants who do not entrain will inspire more concentrated
      aerosols than older children. Once entrainment occurs, the mass of drug inspired
      is largely independent of size. Regimens for nebulised drug delivery in children
      may require revision.

PMID- 1975337
TI  - 5-HT blockers and all that.

PMID- 1975338
TI  - Antenatal screening for toxoplasmosis in the UK.

PMID- 1975339
TI  - The secret of sex?

PMID- 1975340
TI  - The Scots and their hearts.

PMID- 1975341
TI  - Established anticonvulsants and treatment of refractory epilepsy.

PMID- 1975342
TI  - Histamine-2-receptor antagonists and gastric cancer risk.
AB  - The relation between use of histamine-2-receptor (H2-receptor) antagonists and
      gastric cancer risk was investigated in a case-control study in northern Italy.
      563 patients with newly diagnosed, histologically confirmed gastric cancer were
      compared with 1501 controls who did not have neoplastic or gastrointestinal
      disorders. 36 (6.3%) cases and 59 (3.3%) controls had used H2-receptor
      antagonists (cimetidine or ranitidine). The relative risk (RR) for ever-use was
      1.8 (95% confidence intervals [CI] 1.2, 2.7). The increased risk was restricted
      to patients who had started treatment with H2-receptor antagonists within 5 years
      of the diagnosis of stomach cancer (RR 3.1; 95% CI 1.8, 5.3). For first use of H2
      receptor antagonists 5-9 years previously the RR was 1.5 (95% CI 0.7, 3.3), and
      for first use 10 or more years previously RR was 0.2 (95% CI 0.03, 0.8). Although
      the incidence of gastric cancer was raised for the first few years after the
      start of treatment with H2-receptor antagonists, this may reflect misdiagnosis of
      some early gastric cancers. The findings are against long-term persistence of an
      excess risk of gastric cancer in association with use of H2-receptor antagonists.

PMID- 1975343
TI  - Increased risk of large-bowel cancer in Crohn's disease with colonic involvement.
AB  - A cohort of 1655 patients with Crohn's disease diagnosed during 1983 in the
      Uppsala health care region, Sweden, was followed up with respect to the
      occurrence of colorectal cancer to the end of 1984. 12 colorectal cancers were
      diagnosed, yielding an increased overall risk of 2.5. The relative risk was
      similar for males and females. Duration of follow-up did not affect risk.
      Relative risk for disease of the terminal ileum only was 1.0; for terminal ileum
      and parts of colon 3.2; and for colon alone 5.6. Patients in whom Crohn's disease
      was diagnosed before age 30 with any colonic involvement at diagnosis had a
      higher relative risk (20.9) than those diagnosed at older ages (2.2).

PMID- 1975344
TI  - What is known about the prevention of congenital toxoplasmosis?
AB  - The French programme for the prevention of congenital toxoplasmosis consists of
      the diagnosis and treatment with spiramycin of acute infections during pregnancy
      and monthly follow-up of all identified seronegative women. The major flaw is
      that the efficacy of spiramycin in preventing contamination of the fetus, or at
      least in reducing the extent of the infection, has never been evaluated in a
      randomised placebo-controlled clinical trial. Its evaluation would require the
      follow-up of children born to mothers contaminated during pregnancy for more than
      6 months, a goal that is difficult to obtain in current practice. The cost of the
      programme depends largely on the proportion of non-immune women of childbearing
      age. Since the modes of contamination are known and are linked to living habits,
      it should be possible to reduce the risk of infection during pregnancy by
      adequate health education. This approach is still to be evaluated.

PMID- 1975345
TI  - Prion disease.

PMID- 1975346
TI  - Blood pressure and coronary heart disease.

PMID- 1975347
TI  - Death on the ventilator and organ donation.

PMID- 1975348
TI  - Clinical significance of antenatal calyceal dilatation detected by ultrasound.

PMID- 1975349
TI  - Bicarbonate and cytoplasmic pH.

PMID- 1975350
TI  - Factor VIII:C inhibitor associated with monoclonal-antibody-purified FVIII
      concentrate.

PMID- 1975351
TI  - Amaurosis fugax and antiphospholipid antibodies.

PMID- 1975352
TI  - Acute viral hepatitis B in children: lack of chronicity.

PMID- 1975353
TI  - Multiresistant strain of Listeria monocytogenes in septic abortion.

PMID- 1975354
TI  - Experience with toxin bead ELISA in cholera outbreak.

PMID- 1975355
TI  - Thiamine deficiency and sudden deaths.

PMID- 1975356
TI  - Pseudomonas pseudomallei and sudden unexplained death in Thai construction
      workers.

PMID- 1975357
TI  - Distributing ivermectin.

PMID- 1975358
TI  - Halofantrine to prevent falciparum malaria on return from malarious areas.

PMID- 1975359
TI  - Hyperoxaluria in phosphate-treated hypophosphataemic rickets.

PMID- 1975360
TI  - Intestinal humoral immunity in dermatitis herpetiformis.

PMID- 1975361
TI  - Treatment of insomnia with ritanserin.

PMID- 1975362
TI  - Cystic fibrosis genetics in southern Europe.

PMID- 1975363
TI  - Haemolytic-uraemic syndrome in adults.

PMID- 1975364
TI  - Relapse in chronic depressives on withdrawal of L-tryptophan.

PMID- 1975365
TI  - Influenza-related excess mortality in The Netherlands 1989/90.

PMID- 1975366
TI  - Ventricular arrhythmia in secondary syphilis.

PMID- 1975367
TI  - Co-infection with HTLV-I/II and HIV-1.

PMID- 1975368
TI  - Unusual cause of pharyngeal ulcerations in AIDS.

PMID- 1975369
TI  - HIV-2 antibody in a low-risk individual.

PMID- 1975370
TI  - Urticarial reaction to zidovudine.

PMID- 1975371
TI  - Erythropoietin for patient refusing blood transfusion.

PMID- 1975372
TI  - Sterile pyuria and Chlamydia trachomatis.

PMID- 1975373
TI  - Obstacle to early diagnosis of herpes simplex encephalitis via CSF.

PMID- 1975374
TI  - Amputations and Islam.

PMID- 1975375
TI  - Fluvoxamine: an antidepressant with low (or no) epileptogenic effect.

PMID- 1975376
TI  - Evidence from population mixing in British New Towns 1946-85 of an infective
      basis for childhood leukaemia.
AB  - Mortality from leukaemia under age 25 was studied in British New Towns to test
      the hypothesis that leukaemia represents a rare response to a much commoner (but
      unrecognised) infection, the transmission of which is facilitated when large
      numbers of people come together. The density of children was higher in the rural,
      but lower in the overspill, New Towns than in the areas from which their incomers
      originated. Residents of the rural New Towns had greater diversity of origin than
      those of the overspill towns of London and Glasgow. These two factors would
      encourage a greater rise in the postulated underlying infection in the rural
      towns, and in these a significant excess of leukaemia at ages 0-4 was found in
      1946-65. In both sets of towns there was a significant deficit in other age
      groups consistent with immunising effects of the relevant infection. There are
      parallels with feline leukaemia virus infection, in which contrasting
      leukaemogenic and immunising effects occur in different social settings owing
      mainly to differences in intensity of viral exposure.

PMID- 1975377
TI  - Heat-shock protein 65 as a beta cell antigen of insulin-dependent diabetes.
AB  - The primary beta-cell antigen of insulin-dependent diabetes is thought to be a
      protein with a molecular weight of approximately 64 kD. Hyperthermic incubation
      and cytokines such as interleukin 1 beta, gamma interferon, and tumour necrosis
      factor induce synthesis of 64 kD protein by insulinoma cells. By western blot
      techniques, cross-reactivity was found between this 64 kD protein and monoclonal
      antibodies directed against Mycobacterium tuberculosis heat-shock protein 65, but
      not with antibodies directed against a similar epitope of M leprae heat-shock
      protein 65. Binding of M tuberculosis heat-shock protein 65 antibodies to
      interleukin-1 beta-treated cells was inhibited by prior addition of serum from
      insulin-dependent diabetic patients which contained antibodies to 64 kD beta-cell
      antigen. It is suggested that heat-shock protein 65 may be the 64 kD beta-cell
      antigen and that autoreactivity to an epitope of heat-shock protein 65 may confer
      susceptibility to insulin-dependent diabetes mellitus.

PMID- 1975378
TI  - Zidovudine sensitivity of human immunodeficiency viruses from high-risk, symptom
      free individuals during therapy.
AB  - Human immunodeficiency type 1 isolates from 18 initially symptom-free men who
      were treated with zidovudine for 2 years were investigated for drug sensitivity.
      At the start all the men had persistent core antigenaemia; the acquired
      immunodeficiency syndrome developed in 6 during the study. The polymerase chain
      reaction was used to detect mutations at residue 215 of reverse transcriptase, a
      mutation associated with reduced drug sensitivity. After 2 years 16/18 isolates
      were mutant. However, after about 6 months of treatment the mutation was detected
      in only 7 isolates, 4 from individuals who subsequently had AIDS. Limited direct
      virus sensitivity data correlated with the genetic data. The rate of appearance
      of the 215 mutation seemed to correlate with CD4 counts and viral virulence.

PMID- 1975379
TI  - Prevalence of antibody to heterologous circumsporozoite protein of Plasmodium
      vivax in Thailand.
AB  - The distribution in Thailand of antibody to a recently discovered variant of
      circumsporozoite proteins of Plasmodium vivax was determined by enzyme-linked
      immunosorbent assay (ELISA). The ELISA capture antigens were a synthetic peptide
      of the principal variant sequence ANGAGNQPG and a candidate P vivax vaccine that
      contained the predominant repeat sequence GDRAA/DGQPA. Serological evidence of
      recent inoculation with the variant was found throughout Thailand and in migrants
      from Cambodia, Malaysia, and Burma. IgG antibody to the two P vivax
      circumsporozoite proteins was detected in 217 of 804 test sera (27%). Within the
      regions studied the proportion of positive sera specific for the variant epitope
      ranged from 28% to 66%. A vaccine against the predominant repeat domain may
      rapidly select for the variant, which already appears to be widespread within
      Thailand.

PMID- 1975381
TI  - Progress in tuberous sclerosis.

PMID- 1975380
TI  - The 64 K question in diabetes.

PMID- 1975382
TI  - The colon, the rumen, and D-lactic acidosis.

PMID- 1975384
TI  - NHS nursing homes.

PMID- 1975383
TI  - SSPE in the developing world.

PMID- 1975385
TI  - Neurological complications of domoic acid intoxication.

PMID- 1975386
TI  - Neurological deterioration in young adults with phenylketonuria.
AB  - 7 patients with phenylketonuria who developed neurological disability in
      adolescence or early adult life are described. 4 had been diagnosed by routine
      neonatal screening and started a low phenylalanine diet in infancy. 3 were
      diagnosed in early childhood because of developmental delay, and then started
      dietary treatment. Dietary control deteriorated in later years and was withdrawn
      in mid to late childhood. The late neurological deterioration cannot be directly
      ascribed to poor compliance with or cessation of dietary treatment in this small,
      retrospective study--but other likely causes have been excluded and 2 patients
      showed a striking clinical improvement when a strict diet was resumed. Serial
      magnetic resonance images from one of these patients show abnormalities that
      appeared after cessation of dietary treatment and resolved after diet was
      resumed. If these findings are confirmed, strict dietary control into adult life
      would be indicated for at least some patients with phenylketonuria.

PMID- 1975387
TI  - Survival of patients with breast cancer attending Bristol Cancer Help Centre.
AB  - The Bristol Cancer Help Centre (BCHC) was set up in 1979 to offer various
      alternative therapies and treatments for patients with cancer. It attracted much
      public interest and a high demand for its services--and profound medical
      scepticism. In a study beginning in 1986 of 334 women with breast cancer
      attending the centre for the first time between June, 1986, and October, 1987,
      information about the diagnosis was obtained from case notes. Controls were a
      sample of 461 women with breast cancer attending a specialist cancer hospital or
      two district general hospitals. The same information was obtained for the control
      group as for the BCHC group. All patients have been followed up to June, 1988.
      85% of patients with breast cancer attending the BCHC were aged under 55 at
      diagnosis. More than half had experienced recurrence of their disease before
      entry. For patients metastasis-free at entry, metastasis-free survival in the
      BCHC group was significantly poorer than in the controls (relapse rate ratio
      2.85). Survival in relapsed cases was significantly inferior to that in the
      control group (hazard ratio 1.81). For cases metastasis-free at entry to the BCHC
      there was a significant difference in survival between cases and controls,
      confirming the difference in metastasis-free survival. There was no significant
      difference in survival or disease-free survival between the cancer hospital
      controls and other controls.

PMID- 1975388
TI  - Assisted death. Institute of Medical Ethics Working Party on the Ethics of
      Prolonging Life and Assisting Death.

PMID- 1975389
TI  - Congenital toxoplasmosis and TORCH.

PMID- 1975390
TI  - Can lifestyle changes reverse coronary heart disease?

PMID- 1975391
TI  - Deoxyspergualin for liver graft rejection.

PMID- 1975392
TI  - Aetiology of Kaposi's sarcoma.

PMID- 1975393
TI  - Possible transfer of Pneumocystis carinii between immunodeficient patients.

PMID- 1975394
TI  - HTLV-I in Spain.

PMID- 1975395
TI  - Efficacy of ceftazidime in chronic melioidosis with multiple liver abscesses.

PMID- 1975396
TI  - Mutations in Gaucher's disease detected by MspI.

PMID- 1975397
TI  - Genetic markers of familial coronary heart disease.

PMID- 1975398
TI  - Secondary metabolic defects in spinal muscular atrophy type II.

PMID- 1975399
TI  - Permanent disability from dracunculiasis.

PMID- 1975400
TI  - Diagnostic value of free subunits of serum chorionic gonadotropin in testicular
      cancer.

PMID- 1975401
TI  - Precautions with oral live typhoid (Ty 21a) vaccine.

PMID- 1975402
TI  - Does caffeine contribute to postoperative morbidity?

PMID- 1975403
TI  - Coeliac disease.

PMID- 1975404
TI  - Endothelin in plasma and cerebrospinal fluid of patients with subarachnoid
      haemorrhage.

PMID- 1975405
TI  - Applications to Canadian medical schools.

PMID- 1975406
TI  - Cancer registries in Germany.

PMID- 1975407
TI  - Doctors and torture.

PMID- 1975408
TI  - Insight.

PMID- 1975409
TI  - Gallium-transferrin binding in Alzheimer's disease.

PMID- 1975410
TI  - Screening for osteoporosis.

PMID- 1975411
TI  - Diagnosis of hepatic encephalopathy by proton magnetic resonance spectroscopy.

PMID- 1975412
TI  - How robust are early human embryos?

PMID- 1975413
TI  - Hand-operated airway suction device for use in the newborn.

PMID- 1975414
TI  - Chorionic villus sampling.

PMID- 1975415
TI  - Mutation in codon 200 of scrapie amyloid precursor gene linked to Creutzfeldt
      Jakob disease in Sephardic Jews of Libyan and non-Libyan origin.

PMID- 1975416
TI  - Inhibitors to monoclonal antibody purified factor VIII.

PMID- 1975417
TI  - Rapid neonatal diagnosis of von Willebrand's disease by use of the polymerase
      chain reaction.

PMID- 1975418
TI  - Polymerase chain reaction amplification from dried blood spots on Guthrie cards.

PMID- 1975419
TI  - N-butylbenzenesulphonamide, a novel neurotoxic plasticising agent.

PMID- 1975420
TI  - Improved quantification of in vivo 1H NMR spectra by optimization of signal
      acquisition and processing and by incorporation of prior knowledge into the
      spectral fitting.
AB  - Quantification of localized in vivo brain 1H spectra is in general very difficult
      due to excessive spectral overlap. In addition, intensity distortions may result
      from the effects of the NMR pulse sequence on the spins. This paper describes an
      approach to solving these problems. It comprises optimization of the pulse
      sequence; correction of the experimental lineshape; determination of intensity
      distortions, of relative line positions, and of linewidths using model solutions;
      and incorporation of the thus obtained prior knowledge into a nonlinear least
      squares spectral fitting procedure. This approach resulted in greatly improved
      accuracy, precision, and reliability of the quantitation of our in vivo spectra
      of rat brain, and enabled us to estimate absolute metabolite concentrations.

PMID- 1975422
TI  - Function of the hydrophobic transmembrane portion of Thy-1 antigen.
AB  - Thy-1 antigen is anchored in the cell membrane by glycophosphatidyl inositol
      linkages instead of hydrophobic protein domains. The hydrophobic portion of Thy-1
      antigen is cleaved by putative "transamidase." Mutated genes were constructed by
      using site-directed mutagenesis. One mutant gene codes Thy-1 antigen lacking
      carboxy terminal amino acids from 112Cys to 143Leu including cell membrane
      binding amino acid 112Cys. The other mutant gene codes Thy-1 antigen lacking from
      124Trp to 143Leu that includes leucine core portion. DNA transfection analysis
      and Northern blot analysis revealed that hydrophobic portion of Thy-1 antigen is
      essential to express Thy-1 molecule onto the cell surface.

PMID- 1975421
TI  - Interactions of glucagon and free fatty acids with insulin in control of glucose
      metabolism.
AB  - To study the interactions of physiological glucagon and free fatty acids (FFA)
      concentrations with insulin in the control of glucose metabolism, we determined
      in normal subjects the response of endogenous glucose production (EGP) and
      glucose utilization (Rd) to a progressive and moderate increase of insulinemia in
      the presence of glucagon and FFA levels either decreased (somatostatin [SRIF] and
      insulin infusion, C test) or maintained to normal postabsorptive values isolated
      (SRIF + insulin + glucagon infusion, G test; SRIF + insulin + Intralipid
      infusion, IL test) or in association (SRIF + insulin + glucagon + Intralipid
      infusion, IL + G test). Compared with the C test, maintenance of glucagon level
      had only small and inconsistent effects on glucose Rd, but induced a shift to the
      right of the dose-response curve to insulin of EGP (apparent ED50: C test, 10.9
      mU.L-1; G test, 15.2 mU.L-1). Intralipid infusion resulted, whether glucagon was
      substituted or not, in a near total suppression of the insulin-induced increase
      of glucose Rd (Rd at the end of the tests: C test, 6.13 +/- 0.85 mg.kg-1.min-1; G
      test, 7.29 +/- 0.87 mg.kg-1.min-1; IL test, 3.30 +/- 0.65 mg.kg-1.min-1; IL + G
      test, 3.57 +/- 0.42 mg.kg-1.min-1). In the absence of glucagon, substitution
      Intralipid infusion also antagonized the action of insulin on EGP. However, this
      effect was no longer apparent when glucagon was replaced (dose-response curve to
      insulin of EGP during the G and the IL + G test were comparable).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1975423
TI  - Development of AIDS in a cohort of HIV-seropositive homosexual men in Australia.
AB  - The Sydney AIDS Prospective Study is a cohort study of 1057 homosexual men
      enrolled between February 1984 and January 1985. By June 30, 1989, 111 (26.8%) of
      the 414 men who were seropositive for antibodies to human immunodeficiency virus
      (HIV) at enrollment had developed the acquired immunodeficiency syndrome (AIDS).
      On univariate analysis the following baseline factors were significantly
      associated with subsequent development of AIDS: splenomegaly; a lymphocyte count
      less than 1500 x 10(6)/L; a percentage of CD4+ cells less than 20% of the total
      lymphocyte count; an absolute number of CD4+ cells less than 200 x 10(6)/L; and a
      CD4+: CD8+ ratio less than 1.00. In a proportional hazards model the following
      factors retained significance: a lymphocyte count less than 1500 x 10(6)/L; an
      absolute number of CD4+ cells less than 200 x 10(6)/L; and a CD4+: CD8+ ratio
      less than 1.00. A CD4+ cell count less than 200 x 10(6)/L carried the greatest
      relative risk (3.99) for the development of AIDS. This study has confirmed that
      the appreciable rates of progression to AIDS demonstrated in overseas cohorts of
      HIV-infected persons also apply in the Australian context. A number of laboratory
      variables was found to be predictive for the subsequent development of AIDS. As
      we were not able to determine accurately whether subjects were receiving
      antiretroviral treatment or prophylaxis for opportunistic infections the observed
      rates in this study should be seen as minimum estimates. These findings have
      important implications for HIV-infected persons and for public health planning,
      and emphasise the need for regular clinical monitoring and T-cell subset
      enumeration in HIV-infected persons.

PMID- 1975424
TI  - Multiple endocrine neoplasia type 2b: long-term follow-up of a case.
AB  - Multiple endocrine neoplasia type 2b is a rare inherited syndrome which comprises
      the association of medullary thyroid carcinoma, phaeochromocytoma, widespread
      neuromatous proliferation and a characteristic body habitus. In this report we
      present the late clinical course and autopsy findings of the first patient with
      this syndrome described in Australia. At presentation she was found to have a
      right adrenal phaeochromocytoma and medullary thyroid carcinoma which were
      resected in separate operations. No clinical or biochemical evidence of residual
      medullary thyroid carcinoma was identified in life. However, in spite of serial
      vanillylmandelic acid estimations, which showed normal or only mildly elevated
      levels, and normal results of urinary catecholamine studies, a left adrenal
      phaeochromocytoma was identified in a metaiodobenzylguanidine (MIBG) study
      performed 14 years after presentation. Her late clinical course was dominated by
      progressive dysphagia, intestinal dysmotility and megacolon associated with
      unrelenting malnutrition. After her death due to an intracerebral haemorrhage, an
      autopsy confirmed the presence of a left adrenal phaeochromocytoma and revealed
      diffuse intestinal ganglioneuromatosis to be the cause of her intestinal
      dysmotility. No residual medullary thyroid carcinoma was found. This case
      emphasises the propensity for multiple endocrine tumours in these patients and
      highlights the potentially significant role of intestinal ganglioneuromatosis in
      the natural history of this condition.

PMID- 1975425
TI  - Neurotoxicology in the 1990s.
AB  - During the last ten years, neurotoxicology has entered the mainstream of
      environmental toxicology as evidenced by numerous national and international
      conferences, formation of societies related to neurotoxicology, establishment and
      support of journals devoted to neurotoxicology and reliance of regulatory
      agencies on neurotoxicological endpoints. Over the last ten years, agreement
      seems to have been reached concerning the need for and use of neurotoxicological
      tests for hazard identification. With regard to the future of neurotoxicology,
      there are a number of important issues that deserve attention, including 1)
      arriving at a commonly accepted definition of neurotoxicology, 2) the impact of
      new technology, 3) development of biological markers for neurotoxicology, 4)
      neurotoxicology of chemical mixtures, 5) relationship between environmental
      agents and neurodegenerative diseases, 6) use of in vitro procedures in
      neurotoxicology, 7) risk assessment and 8) development of database for specific
      neurotoxicants. The last ten years have been productive ones for neurotoxicology.
      The next ten years should mark a new phase of development marked by significant
      progress in a number of important areas in environmental toxicology.

PMID- 1975426
TI  - Aerosolized pentamidine for prophylaxis against Pneumocystis carinii pneumonia.
      The San Francisco community prophylaxis trial.
AB  - BACKGROUND AND METHODS: Pneumocystis carinii pneumonia (PCP) is the most frequent
      life-threatening opportunistic infection associated with human immunodeficiency
      virus (HIV) infection. To assess the possible value of aerosolized-pentamidine
      prophylaxis in different doses, a controlled clinical trial was begun in 1987
      with 408 subjects at 12 treatment centers. The participants were randomly
      assigned to receive 30 mg of pentamidine every two weeks, 150 mg every two weeks,
      or 300 mg every four weeks. RESULTS: Eighteen months after randomization, the
      subjects in the 300-mg arm had had 8 confirmed episodes of PCP while receiving
      treatment, as compared with 22 in the 30-mg arm (P = 0.0008). The 150-mg arm had
      intermediate results but ones not significantly different from those of the 300
      mg arm. Participants with previous episodes of PCP and CD4-cell counts less than
      200 per cubic millimeter were at the highest risk for PCP. CONCLUSIONS:
      Aerosolized pentamidine was effective for prophylaxis against PCP in patients
      infected with HIV, according to the dose and schedule of administration. It and
      zidovudine were well tolerated together and had independent prophylactic
      benefits.

PMID- 1975427
TI  - Distinct sequence of negative or positive selection implied by thymocyte T-cell
      receptor densities.
AB  - Recent evidence suggests that positive and negative selection of thymocytes
      bearing alpha beta T-cell receptors occurs during the predominant double-positive
      (CD4+CD8+) stage. But the sequence or stage at which positive or negative
      selection occurs during thymocyte maturation has not been well defined. Here we
      use transgenic mice to show that the CD4+CD8+ stage might be further subdivided
      into CD3lo (low) and CD3in (intermediate) stages. The CD3in stage could represent
      T cells that have been positively selected, as this stage is dependent on the
      presence of the appropriate major histocompatibility complex restriction element.
      In addition, we use two different tolerizing antigens to show that negative
      selection may occur either before or after this CD3in stage.

PMID- 1975428
TI  - A truncated human chromosome 16 associated with alpha thalassaemia is stabilized
      by addition of telomeric repeat (TTAGGG)n.
AB  - The instability of chromosomes with breaks induced by X-irradiation led to the
      proposal that the natural ends of chromosomes are capped by a specialized
      structure, the telomere. Telomeres prevent end-to-end fusions and exonucleolytic
      degradation, enable the end of the linear DNA molecule to replicate, and function
      in cell division. Human telomeric DNA comprises approximately 2-20 kilobases (kb)
      of the tandemly repeated sequence (TTAGGG)n oriented 5'----3' in towards the end
      of the chromosome, interspersed with variant repeats in the proximal region.
      Immediately subtelomeric lie families of unrelated repeat motifs (telomere
      associated sequences) whose function, if any, is unknown. In lower eukaryotes the
      formation and maintenance of telomeres may be mediated enzymatically (by
      telomerase) or by recombination; in man the mechanisms are poorly understood,
      although telomerase has been identified in HeLa cells. Here we describe an alpha
      thalassaemia mutation associated with terminal truncation of the short arm of
      chromosome 16 (within band 16p13-3) to a site 50 kb distal to the alpha globin
      genes, and show that (TTAGGG)n has been added directly to the site of the break.
      The mutation is stably inherited, proving that telomeric DNA alone is sufficient
      to stabilize the broken chromosome end. This mechanism may occur in any genetic
      disease associated with chromosome truncation.

PMID- 1975429
TI  - Affinities of full agonists for cardiac beta-adrenoceptors calculated by use of
      in vitro desensitization.
AB  - Positive chronotropic and inotropic responses of guinea-pig isolated
      spontaneously beating right atria and paced left atria to beta-adrenoceptor
      agonists were recorded. Cumulative concentration-response curves for the rate and
      tension responses to isoprenaline, orciprenaline, terbutaline and fenoterol were
      obtained before incubation of the tissues with isoprenaline (10(-6) M), the
      tissues were then washed during 1 h to remove isoprenaline before constructing a
      post-incubation curve to the same agonist. Incubation with isoprenaline for 4 h
      caused parallel rightwards shifts to the curves, but extending the incubation to
      8 h caused additional depression of the rate (85.2 +/- 5.4%) and tension (68.9 +/
      2.3%) maxima. Incubation with isoprenaline for 4 h only shifted the curves for
      orciprenaline to the right but depressed the post-incubation maximum rate and
      tension responses to terbutaline (74.8 +/- 1.5 and 33.8 +/- 2.5%) and fenoterol
      (85.6 +/- 5.5 and 76.0 +/- 5.1%). Thus incubation with isoprenaline for 4 h
      induced desensitization of the cardiac beta-adrenoceptor which was revealed as a
      loss in sensitivity to both isoprenaline and other beta-adrenoceptor agonists.
      The reduced maxima were attributed to a loss of beta-adrenoceptors and exhaustion
      of the receptor reserve. Those experiments displaying the reduced maxima were
      used for calculation of dissociation constants (KA) values by the method of
      Furchgott (1966) for irreversible antagonism. The values for the right atria were
      57 (19-170)nM, 29 (8.4-100)microM and 13 (1.9-8.4)microM and for the left atria,
      89 (15-510)nM, 25 (9.9-64)microM and 18 (7.7-42)microM for isoprenaline (8 h
      incubation), terbutaline and fenoterol respectively.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1975430
TI  - [The value of roentgen studies in supination injuries of ankle and foot].
AB  - In 523 consecutive patients with inversion injuries of ankle and foot, X-ray
      examination revealed 52 fractures. The majority of these fractures could be
      treated symptomatically. On the basis of clinical examination as the diagnostic
      tool for these ankle injuries, the need for radiological assessment was decided.
      All important fractures were recognized. The patient's ability to bear weight on
      the injured ankle, the presence of lateral malleolar tenderness and advanced age
      were important clinical variables. Careful physical examination can lead to a
      selective radiological assessment of acute ankle injuries. Superfluous X-ray
      procedures can be eliminated which will greatly reduce costs without detriment to
      patient care.

PMID- 1975431
TI  - [Increased blink rate in schizophrenic patients].

PMID- 1975432
TI  - [Autosomal dominant polycystic kidney and genetic markers of chromosome 16].
AB  - The mutation for autosomal dominant polycystic kidney disease (APKD) has been
      mapped by linkage analysis on the distal part of the short arm of chromosome 16.
      We present in this study the results of linkage analysis using the two most
      tightly linked DNA markers (3'HVR and 24-1) in 183 members of 14 families of a
      same ethnic origin. We have constructed haplotypes using these two polymorphic
      probes, and compared the frequency of these on the normal and the affected
      chromosome. No evidence of linkage heterogeneity was found in our population.

PMID- 1975433
TI  - Assignment of the X-linked torsion dystonia gene to Xq21 by linkage analysis.
AB  - We performed linkage analysis of X-linked torsion dystonia (XLTD) in 7 Filipino
      families, studying DNA from a total of 36 family members (9 obligate carrier
      females, and 18 affected and 9 unaffected males). Application of 21 informative X
      chromosomal DNA sequences allowed assignment of the XLTD locus to the proximal
      long arm of the X chromosome (Xq21). A maximum LOD score of 3.06 at [symbol: see
      text] = 0.0 was obtained with DXYS2, previously assigned to Xq21.3.

PMID- 1975434
TI  - Abstracts of the eleventh annual conference, the Hong Kong Society of
      Neuroscience. Hong Kong, August 31 and September 1, 1989.

PMID- 1975435
TI  - Abstracts of the eighth national meeting of the Brain Research Association.
      Bristol, U.K., 26-28 March 1990.

PMID- 1975436
TI  - [Effective treatment of theophylline poisoning using a beta adrenergic
      blockader].

PMID- 1975437
TI  - The pharmacology of new anxiolytics acting on 5-HT neurones.
AB  - This paper discusses the alternative approaches available for the development of
      anxiolytics not acting on the benzodiazepine--GABA receptor complex. There are
      now several compounds that work by reducing 5-hydroxytryptamine function in the
      brain that have been shown to have anxiolytic properties in animals and in some
      cases man. Detailed long-term clinical trials are required to determine whether
      these new drugs are clinically useful and avoid the problems associated with
      benzodiazepines.

PMID- 1975438
TI  - Benzodiazepine dependence and the problems of withdrawal.

PMID- 1975439
TI  - Stress, catecholamines, and beta-adrenoceptor blockade.

PMID- 1975440
TI  - Antihistamines--useful in atopic eczema?

PMID- 1975442
TI  - Molecular evolutionary genetics of isozymes: pattern, theory, and application.
AB  - Isozyme studies at the population genetics-ecology interface conducted at the
      Institute of Evolution, University of Haifa, during 15 years, 1974-1989, are
      reviewed in terms of the evidence, theoretical, and practical implications. These
      studies involve numerous individuals, populations, species, and higher taxa in
      nature of plants, animals, and humans tested for variation at 15 to 50 primary
      isozyme loci. The isozyme studies have been conducted mainly in individuals
      sampled in natural populations at the local, regional, and global levels. Two of
      the species studied were wild cereals, the progenitors of wheat and barley in the
      Near East Fertile Crescent. These studies have been complemented by laboratory
      controlled a priori experimentation of inorganic and organic pollution biology.
      The human genetics laboratory compared isozyme structure of Jewish and non-Jewish
      populations. Our results indicate that: (i) isozyme diversity in nature in
      abundant, at least partly adaptive, and is oriented and maintained primarily by
      ecological factors. (ii) Natural selection in action is highlighted by stresses
      involving among others thermal, chemical, and climatic factors. (iii) Speciation
      can occur with little change in isozyme diversity. (iv) Jews from diverse
      countries, and in spite of 2,000 years of Diaspora, retain in the frequencies of
      some isozymes their Near Eastern origins. (v) Wild cereals harbor rich genetic
      resources exploitable in breeding either directly as adaptive structures, or
      indirectly as genetic markers for genotypic production of elite agronomic traits.
      (vi) Isozymes have been utilized as genetic monitors of marine pollution thereby
      contributing to environmental quality and conservation. (vii) Isozymes can
      substantially contribute to conservation biology. (viii) Isozymes have been
      successfully utilized in constructing molecular phylogenies and in revealing new
      sibling species. (ix) Future theoretical and practical directions of isozyme
      studies at the protein and DNA levels are outlined.

PMID- 1975441
TI  - Genetic regulation of acetyltransferases in the Syrian inbred hamster: a model
      for man.

PMID- 1975443
TI  - Primate social behavior--anxiety or depression?
AB  - A review of primate social behavior in different species is presented, with
      particular emphasis on the talapoin monkey and the concept of dominance and how
      this may be related to physiological function. Social behavior in nonhuman
      primates can be used to study both anxiety and depression, depending on the
      precise social setting employed and the way in which the animals are manipulated,
      for example by drugs. Studies relevant to anxiety and depression are described,
      and indicate that the behavior of dominant animals is more susceptible to drugs
      that are known to manipulate levels of anxiety, whereas subordinate animals
      appear more susceptible to treatment with antidepressant drugs.

PMID- 1975444
TI  - The pharmacology of human anxiety.
AB  - The human pharmacology of anxiety disorders, including panic disorder, is
      detailed. The major theories center around the role of benzodiazepine receptor,
      noradrenergic and serotonergic dysfunction. The contribution that challenge tests
      with lactate, hyper- and hypocapnia, beta- and alpha-2-adrenoceptor agonists,
      peptides, pentylenetetrazol, and caffeine make to our understanding of the
      biological basis of anxiety and these major theories are described and discussed.

PMID- 1975445
TI  - Drug discrimination models in anxiety and depression.
AB  - Drug discrimination is a technique for investigating the stimulus properties of
      centrally active drugs. Although many studies have employed animals to
      investigate the stimulus properties of substances used clinically for the
      treatment of anxiety and depression, it would be a mistake to consider the
      internal discriminative stimuli as being related specifically to the anxiolytic
      or antidepressant properties of these drugs. Rather drug cues are better
      considered as relating to the pharmacological action of classes of compounds.
      Thus, benzodiazepine cues generalize to other compounds acting at benzodiazepine
      receptors, but not to substances (anxiolytic or otherwise) acting at 5-HT1A
      receptors. Similarly, antidepressants with different pharmacological properties,
      for example the tricyclic imipramine, or the phenylaminoketone buproprion produce
      distinct, unrelated discriminative stimuli. For this reason, the limits of drug
      discrimination techniques for investigating novel anxiolytic or antidepressant
      drugs should be clearly recognized. Attempts to identify an anxiogenic
      discriminative stimulus using pentylenetetrazole have also been misguided. In
      this technique it has proven difficult to separate unequivocally the
      pharmacological proconvulsant effects of the drug from the psychological
      construct anxiety. Nevertheless, drug discrimination remains a valuable technique
      for investigating pharmacological interactions in animals and man.

PMID- 1975447
TI  - Amnesic trace locked into the benzodiazepine state of memory.
AB  - Rats were trained in a food-rewarded lever-pressing task until they could
      complete an FR10 requirement within the first 120 s of the session, and were
      tested for the retention of this response requirement after having reached this
      criterion. The pharmacological treatment instituted at the time of tests was
      either the same as or different from that used during acquisition. In this state
      dependency (StD) procedure, saline-to-drug as well as drug-to-saline state
      changes produced robust failures to transfer with chlordiazepoxide (CDP) and also
      with yohimbine. Diazepam substituted for, while Ro 15-1788 antagonised, CDP; none
      of several non-benzodiazepine compounds substituted for CDP. Neither food
      deprivation nor extensive overtraining after CDP prevented the failure of
      transfer when animals were tested for drug-to-saline transfer. Another series of
      experiments evaluated the effects of CDP and diazepam in a rat conflict
      procedure. The doses at which CDP and diazepam produced anti-conflict effects
      were similar to those at which failure to transfer occurred in saline-to-drug
      state changes, and higher than those at which such failure occurred in drug-to
      saline state changes. With benzodiazepines, StD of memory retrieval conceivably
      constitutes a parsimonious explanation of the anxiolytic and untoward (amnesic,
      drug dependence) actions of these drugs.

PMID- 1975446
TI  - Effects of antihistaminics on naloxone-induced withdrawal in morphine-dependent
      mice.
AB  - Some histamine H1 (tripelennamine, diphenhydramine and cyclizine) and H2
      (ranitidine and cimetidine) antagonists (1 and 10 mg/kg) were administered to
      morphine-dependent mice to evaluate the changes on naloxone-induced abstinence
      syndrome. When antihistaminics were administered 30 min before naloxone (1 mg/kg)
      on day 4 of morphine addiction, the two doses of three H1 antagonists and the
      higher dose of ranitidine inhibited shaking behavior. Furthermore, the two doses
      of tripelennamine and the higher dose of diphenhydramine, cyclizine and
      cimetidine enhanced jumping behavior. When antihistaminics were administered
      chronically (during the 4 days of morphine addiction), tripelennamine, cyclizine
      and ranitidine (all at 10 mg/kg) inhibited shaking behavior. The three H1
      antihistaminics used enhanced the number of jumps per mouse whereas ranitidine
      decreased this response. No significant changes were found in the rest of the
      withdrawal symptoms after the antihistaminics were administered. The
      participation of serotonergic and catecholaminergic mechanisms is discussed.

PMID- 1975448
TI  - Double blind comparative study of remoxipride and haloperidol in acute
      schizophrenic patients.
AB  - In the present 6-week double-blind, randomised, multicentre study, the atypical
      neuroleptic remoxipride was compared to haloperidol in acute schizophrenic
      patients (DSM-III). Seventy-one patients entered the study, 36 in the remoxipride
      group and 35 in the haloperidol group. There were ten early withdrawals, four in
      the remoxipride group and six patients in the haloperidol group. The Present
      State Examination (PSE) profile revealed a similar reduction in the symptom
      clusters of psychosis in both treatment groups. Forty-seven per cent of the
      patients in the remoxipride group and 34% of the patients in the haloperidol
      group showed clinically relevant improvement (reduction of BPRS total score
      greater than or equal to 50%). All extrapyramidal symptoms except "glabella tap"
      occurred significantly less frequently in the remoxipride group as compared to
      the haloperidol group. Substantially lower incidences of EPS were found by active
      questioning in the remoxipride group compared to the haloperidol group. In
      addition, considerably lower incidences were observed in the remoxipride group
      with respect to drowsiness/somnolence, tiredness/fatigue and concentrating
      difficulty. At the end of treatment 66% of the patients in the haloperidol group
      and 22% in the remoxipride group were using anticholinergics. No consistent
      changes were found in the mean plasma HVA level in either treatment group. In
      responders (reduction of BPRS total score greater than or equal to 50%) lower
      baseline HVA levels were observed in both treatment groups. This study indicates
      that the newly developed neuroleptic remoxipride is an effective antipsychotic
      compound, which is clinically safe and well tolerated. In particular, few EPS
      were induced by remoxipride, as compared to haloperidol.

PMID- 1975449
TI  - Characterisation of the phenomenon of "one-trial tolerance" to the anxiolytic
      effect of chlordiazepoxide in the elevated plus-maze.
AB  - In the elevated plus-maze test of anxiety the scores of control animals remain
      stable over repeated tests. However, a single prior exposure to the plus-maze
      renders an animal insensitive to the anxiolytic effects of chlordiazepoxide. This
      phenomenon of "one-trial tolerance" persisted even when the two trials were
      separated by as much as 2 weeks. It has previously been shown that the drug state
      of the animal on trial 1 is not important to the development of the phenomenon,
      but one-trial tolerance did not develop if a very high dose (75 mg/kg) of
      chlordiazepoxide was given on trial 1; it is suggested that this is due to the
      amnesic effects of the drug. The learning on trial 1 was not specific to a
      particular plus-maze and tolerance could be observed even when the maze on trial
      1 was made from different material. The crucial experience on trial 1 was
      experience of an open arm of the maze. Whereas tolerance could be obtained as a
      result of a previous plus-maze experience, there was no evidence of an anxiogenic
      withdrawal response when rats were tested the following day undrugged. The
      phenomenon of one-trial tolerance is explained within our recently proposed two
      factor theory of benzodiazepine dependence; it is suggested that one-trial
      tolerance provides a method for studying the mechanism underlying the development
      of tolerance to anxiolytic effects, independently from the mechanism underlying
      the development of withdrawal responses.

PMID- 1975450
TI  - [Glue instead of solder].

PMID- 1975451
TI  - Regulation of glutamate and aspartate release from the Schaffer collaterals and
      other projections of CA3 hippocampal pyramidal cells.
AB  - Excitatory synaptic transmission in the CNS can be modulated by endogenous
      substances and metabolic states that alter release of the transmitter, usually
      glutamate and/or aspartate. To explore this issue, we have studied the release of
      endogenous glutamate and aspartate from synaptic terminals of the CA3-derived
      Schaffer collateral, commissural and ipsilateral associational fibers in slices
      of hippocampal area CA1. These terminals release glutamate and aspartate in about
      a 5:1 ratio. The release process is modulated by adenosine, by the transmitters
      themselves and by nerve terminal metabolism. Adenosine inhibits the release of
      both amino acids by acting upon an A1 receptor. The transmitters, once released,
      can regulate their further release by acting upon both an NMDA and a non-NMDA
      (quisqualate/kainate) receptor. Activation of the NMDA receptor enhances the
      release of both glutamate and aspartate, whereas activation of the non-NMDA
      receptor depresses the release of aspartate only. Superfusion of CA1 slices with
      a glucose-deficient medium increases the release of both amino acids and reduces
      the glutamate/aspartate ratio. These results have implications for the regulation
      of excitatory synaptic transmission in the CA1 area and for the mechanism of
      hypoglycemic damage to CA1 pyramidal cells.

PMID- 1975452
TI  - Dendritic excitation by glutamate in CA1 hippocampal cells.
AB  - In order to reveal properties and effects of glutamate excitation, CA1 pyramidal
      cells in rat hippocampal slices were impaled and responses to iontophoresis of
      glutamate onto sensitive spots in the dendrites were analyzed. The glutamate
      elicited response consisted of a steady depolarization; its amplitude was dose
      dependent. The cellular response to repeated applications of glutamate showed a
      striking degree of stability. Both dendritic and somatic depolarization, induced
      by glutamate and current, respectively, elicited similar discharge patterns. The
      sensitivity to glutamate was highly localized, corresponding to the dendritic
      tree of a given cell. Short, repeated glutamate pulses did not interfere with an
      orthodromic test response, whereas longer glutamate ejections often depressed the
      EPSP. Combined temporal and spatial pairing of glutamate and orthodromic
      activation was followed by a lasting increase in synaptic efficiency, similar to
      LTP.

PMID- 1975453
TI  - Increases in glutamate release and phosphoinositide metabolism associated with
      long-term potentiation and classical conditioning.
AB  - Long-term potentiation (LTP) is a widely studied model of the kind of activity
      dependent modulation of synaptic efficacy which is assumed to provide the
      physical basis for learning. Whether LTP, in the hippocampus or elsewhere in the
      brain, does in fact serve such a role is still a matter for debate. One approach
      to answering this question is to identify physiological or biochemical changes
      which are common to both learning and LTP; in the hippocampus, for example, one
      can ask whether the biochemical changes associated with LTP are also associated
      with learning. In this chapter we summarize the results which we have obtained in
      a study of glutamate release and phosphoinositide turnover in the dentate gyrus
      of rats trained in a classical conditioning task. The similarity between the
      changes occurring after classical conditioning and those associated with LTP is
      consistent with the hypothesis that LTP is one of the mechanisms by which a
      neural trace of the learned association is formed. We discuss this interpretation
      in the light of the observation that classical conditioning does not appear to
      affect synaptic responses in the hippocampus.

PMID- 1975454
TI  - Similarities in circuitry between Ammon's horn and dentate gyrus: local
      interactions and parallel processing.
AB  - We present a "model" of hippocampal information processing based on a review of
      recent data regarding the local circuitry of Ammon's horn and the dentate gyrus.
      We have been struck by the parallels in cell type and connectivity in Ammon's
      horn and the dentate gyrus, and have focused on similarities between CA3
      pyramidal cells and mossy cells. Important conclusions of our analysis include
      the following: (1) The idea of serial processing of afferent information, from
      one hippocampal subregion to the next, is inadequate and based on an over
      simplification of circuitry; information processing undoubtedly occurs over
      parallel, as well as serial, pathways. (2) Local circuitry within a given
      hippocampal subregion gives rise predominantly to feedforward inhibition;
      recurrent inhibition is present, but less potent. (3) There are multiple
      populations of local circuit neurons, each of which has a specific function,
      characteristic interconnections, and special cell properties. It is misleading to
      categorize these cells into a single category of inhibitory interneuron.

PMID- 1975455
TI  - A quantitative electron microscopic immunocytochemical study of the distribution
      and synaptic handling of glutamate in rat hippocampus.
AB  - One of the major problems in glutamate immunocytochemistry has been the
      difficulty involved in separating immunocytochemical labelling due to metabolic
      glutamate from the labelling caused by transmitter glutamate. Another problem
      appears to be the accessibility of antigenic sites in conventional light
      microscopic preparations. In the present report, we have applied the primary
      glutamate antiserum onto ultrathin tissue sections, followed by the use of a
      colloidal gold detection system. The use of this postembedding immunogold
      procedure allows equal access of antibodies to all cellular compartments exposed
      at the section surface, allows quantitative assessment of the immunoreactivity,
      and affords a high resolution compatible with studies at the organelle level.
      When applied to slice preparations the immunogold procedure can be used to
      identify releasable pools of glutamate. These methodological advances have
      greatly increased the usefulness of glutamate immunocytochemistry as a tool to
      study putative glutamatergic terminals in the CNS.

PMID- 1975456
TI  - [Diagnosis using DNA studies].

PMID- 1975457
TI  - Genetic and serologic relatedness between Mycoplasma fermentans strains and a
      mycoplasma recently identified in tissues of AIDS and non-AIDS patients.
AB  - A mycoplasma previously identified in the tissues of both AIDS and non-AIDS
      patients dying of an acute fatal disease was earlier shown to share some biologic
      and genetic properties with a strain of Mycoplasma fermentans, an organism
      occurring infrequently in the human lower urogenital tract. More extensive
      genetic and serologic comparisons using DNA/DNA hybridization, DNA base
      composition (guanine + cytosine), restriction endonuclease DNA analysis, cellular
      protein patterns and metabolism inhibition serologic procedures confirm that the
      organism previously designated as "Mycoplasma incognitus" (Mi) is indeed very
      closely related to strains of M. fermentans. While the genetic and serologic
      features observed among the newly isolated mycoplasma and two M. fermentans
      strains suggest a species relationship, it now seems useful to re-examine the
      biological activities of other freshly isolated M. fermentans strains from man.

PMID- 1975458
TI  - [Therapy of bronchus carcinoma: therapeutic possibilities and current molecular
      biology trials].
AB  - Clearcut progress has been achieved in the treatment of lung cancer in the last
      decade. While small cell lung cancer has proven a highly chemosensitive tumor,
      only remissions of relatively short duration are obtained. The high relapse rate
      is probably due to the reappearance of chemoresistant subclones. In contrast, non
      small cell lung cancer is often chemoresistant from the outset, a fact which
      limits the therapeutic possibilities in these tumors. Different forms of
      chemoresistance are described and potential modalities of circumventing or
      reversing it are discussed. In recent years, greater insight into molecular
      mechanisms of tumor formation has been achieved. The role of activation or
      overexpression of oncogenes has been demonstrated. More recently the role of
      tumor suppressor gene inactivation has become evident. By means of restriction
      fragment length polymorphism (RFLP) a combination of gene deletions in various
      chromosomes has been demonstrated in lung cancer. The pattern of chromosomes
      involved appears to vary between small cell and non small cell lung cancer. It is
      to be hoped that these new insights will be translated into new treatment
      modalities for lung cancer.

PMID- 1975459
TI  - [Dental accidents. Accidents to the permanent teeth in the youthful dentition].

PMID- 1975460
TI  - [Occupational dental diseases].

PMID- 1975461
TI  - Multiple endocrine neoplasia type 1--presenting with impotence.
AB  - A 35-year old man presented with a 4-year history of impotence. His past history
      was significant for hypercalcaemia, bilateral pyelolithotomies for renal calculi
      and parathyroidectomy for hyperparathyroidism. He had an episode of haemetemesis
      and malaena a year before being seen here. Endocrine investigations revealed
      hyperprolactinemia, hypergastrinemia and increased basal acid output. Magnetic
      resonance imaging of the brain was indicative of a pituitary microadenoma.
      Computed tomographic scan of the abdomen revealed a bulky pancreas which was
      suggestive of a gastrin-secreting islet cell tumour. This case illustrates an
      unusual presentation of multiple endocrine neoplasia type 1 (MEN-1) with
      impotence and hyperprolactinemia. A short review of the literature was done.

PMID- 1975462
TI  - [Comparative clinical characteristics of rheumatic and reactive arthritis].
AB  - The difficulties encountered in differential diagnosis of rheumatic and reactive
      arthritides are caused by the similarity of the articular syndrome not
      infrequently seen in both diseases, especially in their acute phases, a high
      frequency of little manifest forms of rheumocarditis and the rarity of other main
      manifestations of rheumatic fever as well as by a possibility of myocardial
      derangement in reactive arthritides. At the same time of paramount diagnostic
      importance are a detailed study of the disease history, estimation of the
      epidemic situation, careful clinical assessment of the character and evolution of
      the articular syndrome, the signs of lesions of the heart, other organs and
      symptoms, recognition of the symptoms characteristic for diseases of the group of
      seronegative spondylarthropathies, particularly Reiter's syndrome.

PMID- 1975463
TI  - Trends and district variations in the hospital care of childhood asthma: results
      of a regional study 1970-85.
AB  - Trends and district variations in the pre-hospital and hospital care of children
      aged 0-14 years admitted with acute asthma were surveyed in all 13 districts of a
      health region by examining case notes for 1970, 1978, and 1985. From 1970 to 1985
      there was a substantial increase in admissions and some reduction of hospital
      stay. Over this time adrenergic drugs remained the most frequently used treatment
      with a large shift towards selective beta2 agonists administered by nebulisation.
      Use of corticosteroids fell in the under 5s with a decrease in the parenteral
      route of administration but rose in the 5-14 age group with an increase in the
      oral route of administration. There was an increase the use of oral xanthines but
      this was outweighed by falls in the use of suppositories and in parenteral
      administration. The use of antibiotics became less frequent and that of sedatives
      and antihistamines fell to almost nil. There were also important changes in other
      aspects of management, notably an increase in the use of lung function tests
      (from 3% to 70%) and falls in the use of chest radiographs, blood tests,
      bacteriology, and physiotherapy. In nearly all aspects of management there were
      significant and often very extreme variations in practice between districts,
      which were unlikely to be explained by differences in morbidity. These variations
      would be a suitable focus for medical audit, with the aim of establishing which
      treatment regimens have the best outcome and avoiding unnecessary cost and
      discomfort. Because early hospital drug treatment is closely related to the type
      of treatment given before admission such audit activities would need to include
      general practitioners.

PMID- 1975464
TI  - Placental and blood-brain barrier transfer following prenatal and postnatal
      exposures to neuroactive drugs: relationship with partition coefficient and
      behavioral teratogenesis.
AB  - In order to determine the neurotoxicity of prenatal and postnatal exposures to
      neuroactive drugs in developing rats, we examined placental and blood-brain
      barrier (BBB) transfers of these radiolabeled drugs when they were administered
      sc to pregnant rats on Day 19 of gestation, and to pups on Days 2, 7, and 14
      after birth. The logarithms of partition coefficients (log Pcorr), used as
      indices of the lipid solubility of the drugs, decreased in the order propranolol
      greater than chlorpromazine greater than haloperidol greater than atropine
      greater than reserpine greater than dopamine greater than epinephrine greater
      than norepinephrine. The coefficients of correlation between log Pcorr and BBB
      transfer were statistically significant in all dams, fetuses, and pups.
      Propranolol, chlorpromazine, and haloperidol, having high lipid solubility,
      passed rapidly into fetuses. Behavioral teratogenesis occurred to a greater
      extent with postnatal than with prenatal exposures. All moderately and poorly
      lipophilic drugs transferred into fetuses, although at lower plasma
      concentrations than in dams. BBB transfer was low in dams, fetuses, and pups. The
      behavioral teratogenic potential of these drugs was relatively weaker than that
      of highly lipophilic drugs. Our results suggest that BBB transfer of drugs, which
      varies according to lipid solubility, is a major factor in behavioral
      teratogenesis. Highly lipid-soluble drugs were readily incorporated into
      developing rat brains, becoming strongly behaviorally teratogenetic by impairing
      postnatal functional maturation.

PMID- 1975465
TI  - Intracellular cesium separates two glutamate conductances in retinal bipolar
      cells of goldfish.
AB  - The responses of depolarizing bipolar cells to glutamate were investigated in the
      superfused isolated goldfish retina. In intracellular recordings with potassium
      filled microelectrodes, glutamate hyperpolarized cells but did not alter the net
      input conductance. In recordings with cesium-filled microelectrodes, the
      glutamate-evoked hyperpolarization was associated with a net conductance
      decrease. In the presence of internal cesium, glutamate action had the same
      reversal potential as the actions of the glutamate analog 2-amino-4
      phosphonobutyrate (APB) and the rod transmitter, suggesting that all three of
      these substances act at the same class of receptor. We propose that glutamate
      acts both at the APB-sensitive receptor that mediates rod inputs and at another
      receptor type that produces a conductance increase, is blocked by cesium, and may
      mimic the action of the cone transmitter.

PMID- 1975466
TI  - [Maldescensus testis and testicular tumors. Personal experiences].
AB  - In 236 own patients suffering from malignant testicular tumors a maldescensus
      testis was evaluated in childhood. Because of increased risk of cancer in
      maldescended testis attention should be paid also after successful orchiopexy.

PMID- 1975467
TI  - [The welding of cobalt-chromium, nickel-chromium and silver-palladium alloys
      using a solid-state laser].

PMID- 1975468
TI  - Rectal carcinoid tumor metastasizing to the thyroid and pancreas. An autopsy case
      exploiting immunohistochemistry for differentiation from tumors involving
      multiple endocrine organs.
AB  - A 58-year-old male patient with rectal carcinoid tumor is presented. The tumor
      extensively involved the lymph nodes and liver, and multiple tumors were also
      recognized in the pancreas and thyroid. Grossly, it was uncertain whether the
      latter were metastases from the rectal carcinoid or all were coincident primary
      tumors involving multiple endocrine organs, so-called multiple endocrine
      neoplasia (MEN) syndrome. Histologic, histochemical and electron microscopic
      examinations of the tumors in both the pancreas and thyroid showed similar
      features to those of the rectal carcinoid. The neoplastic cells in all involved
      organs commonly expressed positive immunoreactivity for somatostatin, but
      negativity for carcinoembryonic antigen, calcitonin, calcitonin gene-related
      peptide, thyroglobulin, insulin, glucagon and pancreatic polypeptide. These
      immunohistochemical results confirmed that the tumors observed in multiple
      endocrine organs were indeed metastatic from the rectal carcinoid, rather than
      being a new combination of MEN syndrome. Some neuroendocrine tumors may develop
      widespread metastasis, sometimes creating problems with differentiation from
      multiple primary endocrine tumors. Immunohistochemistry may be of great help in
      setting this issue.

PMID- 1975469
TI  - Post-mortem changes of neurotransmitter concentrations in the rat brain regions.
AB  - Using High Performance Liquid Chromatography coupled with electrochemical
      detection the post-mortem stability of noradrenaline (NA), dopamine (DA),
      serotonin (5-HT) and 5-hydroxy indole acetic acid (5-HIAA) were examined in the
      rat hypothalamus, amygdala, cerebral cortex, cerebellum and corpus striatum over
      an 8 hour time period. Changes in concentrations of the different
      neurotransmitters were less than it might be expected. The significant changes
      were: a. A fall in NA levels in the cerebral cortex by 4 hours and in the
      hypothalamus at 8 hours. b. A reduction in DA concentrations in the corpus
      striatum at 8 hours but a two fold rise of levels in the hypothalamus at 1 and 2
      hours. c. A four-fold increase in 5-HT concentrations in the amygdala throughout
      the 8 hours studied. The results indicate that for comparative studies on post
      mortem brain tissue correction factors should be employed to take into account
      differential changes in the concentrations of the various neurotransmitters.

PMID- 1975470
TI  - Adrenergic dependence of the platelet aggregation in rats.
AB  - The paper examines the effect of different adrenergic agents influencing both the
      neuronal unit of the adrenergic transmitter system and its alpha- and beta
      receptor components on the ADP-induced platelet aggregation. A considerable
      inhibition of the platelet aggregation is found under conditions of post
      reserpine adrenergic block (16.06%, p less than 0.001) and blocking of the beta 1
      adrenergic receptors with practolol, applied independently (45.06%, p less than
      0.001) and prior to the treatment of the rats with dobutamine--beta 1
      adrenoreceptor agonist (52.20%, p less than 0.001). The stimulation of these
      receptors with dobutamine accelerates the platelet aggregation by 41.04% (p less
      than 0.001). No changes in the platelet aggregation are found after treatment
      with phenoxybenzamine (nonselective alpha adrenergic blocker) and salbutamol
      (beta 2-adrenergic agonist). It may be concluded that the ADP-induced platelet
      aggregation depends to a certain extent on the functional state of the neuronal
      and beta-adrenoreceptor unit of the adrenergic transmitter system and possibly
      also on the metabolic processes connected with them.

PMID- 1975471
TI  - [Immunological status of patients with recurrent herpes simplex infections. In
      vitro effect of thymopoietin and splenin-derived and partially modified peptides
      on peripheral blood lymphocytes in comparison to a thymus extract].
AB  - Immunological studies on 20 patients with frequently recurrent Herpes simplex
      labialis were performed. Disorders of the cell-mediated immunity were often
      observed which do not only occur during the relapses. The number of T cells and
      their function were especially reduced. On the other hand there were no
      alterations of the CD4/CD8 ratio and the suppressor-activity. In vitro studies
      with peptides of thymopoietin and splenin justify the assumption that these
      peptides have therapeutic effects in recurrent herpes simplex infections.

PMID- 1975472
TI  - Role of left ventricular dysfunction in selective neurohumoral activation in the
      recovery phase of anterior wall acute myocardial infarction.
AB  - Neurohumoral activation is readily apparent in patients with symptomatic
      congestive heart failure (CHF) and in the acute phase after acute myocardial
      infarction. In this study, the neurohumoral profiles of 36 asymptomatic patients
      in the early convalescent phase after acute myocardial infarction were examined.
      All patients in the study had a radionuclide ejection fraction less than or equal
      to 45% and underwent cardiac catheterization 11 to 30 days after infarction.
      Venous blood samples were obtained in the supine state for the measurement of
      norepinephrine, angiotensin II, plasma renin activity and aldosterone in all
      patients. Despite the reduced ejection fraction and extensive wall motion
      abnormalities, plasma norepinephrine was not elevated and did not correlate with
      any measured hemodynamic, angiographic or clinical variables. The renin
      angiotensin II aldosterone system was activated, as expected, in the 9 study
      patients receiving loop diuretics. However, even in the 27 patients not taking
      diuretics, plasma angiotensin II and renin activity levels were increased in
      relation to Killip classification, the presence of a left ventricular (LV)
      aneurysm and LV ejection fraction. Activation of the renin-angiotensin
      aldosterone system can be identified in hemodynamically compensated
      postinfarction patients not taking diuretics and appears to be related to the
      extent of LV dysfunction.

PMID- 1975473
TI  - Usefulness of bucindolol in congestive heart failure.
AB  - The sympathetic hyperactivity of congestive heart failure (CHF) may worsen
      cardiovascular function by down-regulation of myocardial beta-receptors. For this
      reason, beta blockade is proposed to be useful in CHF. Bucindolol is a new beta
      blocker that has intrinsic nonadrenergically-mediated vasodilation and may be
      valuable in treatment of CHF. To test this, 19 patients with CHF were randomized
      in a double-blind protocol to 3 months of treatment with bucindolol (n = 12) or
      placebo (n = 7). Significant improvement was seen in the bucindolol group using
      invasive and noninvasive tests; treadmill time increased from 445 to 530 seconds
      (p = 0.04), Minnesota Living With Heart Failure Questionnaire score improved from
      61 to 40 (p = 0.0001), cardiac output increased from 4.0 to 4.7 (p = 0.02), and
      systemic vascular resistance decreased from 1,888 to 1,481 (p = 0.04). Also, peak
      exercise heart rate and pulmonary capillary wedge pressure decreased
      significantly with treatment. There were no changes in the placebo group. We
      conclude that bucindolol may be an effective treatment for CHF when administered
      chronically and that its nonadrenergic vasodilation may be an important feature.

PMID- 1975474
TI  - A clinically homogeneous group of families with facioscapulohumeral (Landouzy
      Dejerine) muscular dystrophy: linkage analysis of six autosomes.
AB  - Facioscapulohumeral muscular dystrophy (FSHMD) is a neuromuscular disorder
      characterized by autosomal dominant inheritance and clinical onset in the muscles
      of the face and shoulder girdle. Using a set of RFLP markers spaced at
      approximately 20 centimorgans, we have begun a systematic search for markers
      linked to the disease. A total of 81 RFLP loci on six autosomes (1, 2, 5, 7, 10,
      and 16) have been examined for linkage to FSHMD in 13 families. With the computer
      program CRI-MAP, two-point and multipoint analyses have not resulted in any LOD
      score indicative of linkage to FSHMD. However, these analyses have allowed us to
      exclude 909 centimorgans (sex average) of our genetic maps in intervals where the
      LOD score is less than -2.0. We estimate our data have excluded 23% of the human
      genome.

PMID- 1975475
TI  - A locus for familial hypertrophic cardiomyopathy is closely linked to the cardiac
      myosin heavy chain genes, CRI-L436, and CRI-L329 on chromosome 14 at q11-q12.
AB  - We report that a gene responsible for familial hypertrophic cardiomyopathy (HC)
      is closely linked to the cardiac alpha and beta myosin heavy chain (MHC) genes on
      chromosome 14q11. We have recently shown that probe CRI-L436, derived from the
      anonymous DNA locus D14S26, detects a polymorphic restriction fragment that
      segregates with familial HC in affected members of a large Canadian family. Using
      chromosomal in situ hybridization, we have mapped CRI-L436 to chromosome 14 at
      q11-q12. Because the cardiac MHC genes also map to this chromosomal band, we have
      determined the genetic distances between the cardiac beta MHC gene, D14S26, and
      the familial HC locus. Data presented here show that these three loci are linked
      within 5 centimorgans on chromosome 14 at q11-q12. The possibility that defects
      in either the cardiac alpha or beta MHC genes are responsible for familial HC is
      discussed.

PMID- 1975476
TI  - Genetic mapping of two new DNA markers in Xq26-q28 relative to the fragile-X
      syndrome locus.
AB  - We have characterized and genetically mapped two new DNA markers (DXS311 and
      DXS312) with respect to 10 existing loci in Xq26----Xq28 in a set of 15 families
      in which the fragile-X [fra(X)] syndrome was segregating. Two-point and
      multipoint linkage analyses were performed taking into account the incomplete
      penetrance of the fra(X) mutation. The most likely order on the basis of these
      data is centromere-DXS79-DXS10-DXS311-DXS86-(F9-DXS99 )-(DXS98-DXS312)-fra(X)
      DXS52- DXS15-F8C-telomere. DXS98 and one of the new loci, DXS312, were found to
      be the proximal markers closest to the fra(X) locus. The order F9-(DXS98-DXS312)
      fra(X) was found to be 5.9 x 10(4) times more likely than the order (DXS98
      DXS312)-F9-fra(X).

PMID- 1975477
TI  - Alpha 1-antitrypsin Null(isola di procida): an alpha 1-antitrypsin deficiency
      allele caused by deletion of all alpha 1-antitrypsin coding exons.
AB  - alpha 1-Antitrypsin (alpha 1AT) deficiency, a common hereditary disorder
      responsible for emphysema in Caucasians of northern European descent, is caused
      by single base substitutions, deletions, or additions in the seven exons (IA-IC
      and II-V), of the 12.2-kb alpha 1AT gene located on chromosome 14 at q31-32.3. Of
      the five known representatives of the "null" group of alpha 1AT-deficiency
      alleles (alpha 1AT genes incapable of producing alpha 1AT protein detectable in
      serum) evaluated at the gene level, all result from mutations causing the
      formation of stop codons in coding exons of the alpha 1AT gene. The present study
      identifies an alpha 1AT allele (referred to as "Null(isola di procida")) caused
      by complete deletion of the alpha 1AT coding exons. The Null(isola di procida)
      allele was identified in an individual with heterozygous inheritance of
      M(procida) (an allele associated with alpha 1AT deficiency) and a null allele.
      Although results of karyotypic analysis were normal, quantification of the copies
      of alpha 1AT genes in this individual revealed that the index case had only half
      the normal copies of alpha 1AT genes. Cloning and mapping of the Null(isola di
      procida) gene demonstrated a deletion of a 17-kb fragment that included exons II
      V of the alpha 1AT structural gene. As a consequence of the deletion, the normal
      noncoding exons (IA-IC) were followed by exons II-V of the downstream alpha 1AT
      like gene. Sequence analysis of the deletion demonstrated a 7-bp repeat sequence
      (GAGGACA) both 5' to the deletion and at the 3' end of the deletion, a 4-bp
      palindromic sequence (ACAG vs. CTGT) bracketing the deletion, and a novel
      inserted 4-bp sequence (CCTG) at the breakpoint, suggesting that the mechanism of
      the deletion may have been "slipped mispairing."

PMID- 1975478
TI  - Variation at the apolipoprotein (apo) AI-CIII-AIV gene cluster and apo B gene
      loci is associated with lipoprotein and apolipoprotein levels in Italian
      children.
AB  - We have used RFLPs of the apolipoprotein (apo) B gene and apo AI-CIII-AIV gene
      cluster to estimate the genetic contribution of variation at these loci to the
      variability of plasmid lipid, lipoprotein, and apolipoprotein levels in 209
      children from Sezze in central Italy. The sample was randomly divided into group
      I (107 children) and group II (102 children). Four site polymorphisms (PvuII,
      XbaI, MspI, and EcoRI) of the apo B gene and five site polymorphisms (XmnI, PstI,
      SstI, PvuII-CIII, and PvuII-AIV) of the apo AI-CIII-AIV gene cluster were
      examined in group I children. After adjustment for gender, age, and body-mass
      index, polymorphisms at both gene loci (PvuII-B, PvuII-CIII, and PvuII-AIV) were
      associated with significant effects on the levels of plasma apo AI, apo B, or
      high-density lipoprotein-cholesterol. RFLPs that showed significant effects in
      group I were genotyped in group II. All three polymorphisms were associated with
      similar effects on apolipoprotein levels, though for all RFLPs the magnitude of
      the effects was smaller in the group II children and only statistically
      significant for the effect of the PvuII-B genotype on apo AI levels. In the total
      sample of 209 children 7.4% of the sample variance in apo AI levels was explained
      by variation associated with the apo B PvuII-B RFLP. In addition, the PvuII-B
      RFLP was associated with significant effects on plasma apo B levels and explained
      5.7% of the sample variance. The PvuII-CIII and PvuII-AIV polymorphisms were both
      associated with differences in apo AI levels, explaining 3.7%-5.7% of the sample
      variance. Taken together, the three PvuII polymorphisms explained 17.7% of the
      phenotypic variance in apo AI levels. There was significant evidence for an
      effect of nonlinearity of the PvuII-CIII genotypes on apo AI levels, with the
      individuals heterozygous for the polymorphism having the highest apo AI levels.
      No evidence of interaction between genotype and gender, age, and body-mass index
      was shown by covariance analysis. The molecular explanation of this effect is
      unclear. Our data show that variation at both the apo AI-CIII-AIV and apo B loci
      are associated with lipoprotein and apolipoprotein levels in this sample of
      Italian children.

PMID- 1975479
TI  - Application of DNA fingerprints for cell-line individualization.
AB  - DNA fingerprints of 46 human cell lines were derived using minisatellite probes
      for hypervariable genetic loci. The incidence of 121 HaeIII DNA fragments among
      33 cell lines derived from unrelated individuals was used to estimate allelic and
      genotypic frequencies for each fragment and for composite individual DNA
      fingerprints. We present a quantitative estimate of the extent of genetic
      difference between individuals, an estimate based on the percentage of
      restriction fragments at which they differ. The average percent difference (APD)
      among pairwise combinations from the population of 33 unrelated cell lines was
      76.9%, compared with the APD in band sharing among cell lines derived from the
      same individual (less than or equal to 1.2%). Included in this survey were nine
      additional cell lines previously implicated as HeLa cell derivatives, and these
      lines were clearly confirmed as such by DNA fingerprints (APD less than or equal
      to 0.6%). On the basis of fragment frequencies in the tested cell line
      population, a simple genetic model was developed to estimate the frequencies of
      each DNA fingerprint in the population. The median incidence was 2.9 X 10(-17),
      and the range was 2.4 X 10(-21) to 6.6 X 10(-15). This value approximates the
      probability that a second cell line selected at random from unrelated individuals
      will match a given DNA fingerprint. Related calculations address the chance that
      any two DNA fingerprints would be identical among a large group of cell lines.
      This estimate is still very slight; for example, the chance of two or more common
      DNA fingerprints among 1 million distinct individuals is less than .001. The
      procedure provides a straightforward, easily interpreted, and statistically
      robust method for identification and individualization of human cells.

PMID- 1975481
TI  - Calcification of vascular lesions in Takayasu's disease.

PMID- 1975480
TI  - Synaptophysin: structure of the human gene and assignment to the X chromosome in
      man and mouse.
AB  - Synaptophysin is an integral membrane protein of small synaptic vesicles in brain
      and endocrine cells. We have determined the structure and organization of the
      human synaptophysin gene and have established the chromosome localizations in man
      and mouse. Analysis of a cosmid clone containing the human synaptophysin gene
      (SYP) revealed seven exons distributed over approximately 20 kb, when compared
      with the previously published cDNA sequence. The exon-intron boundaries have been
      identified and do not correlate with functional domains. One intron interrupts
      the 3' untranslated region. Chromosomal localization of the human and murine
      genes for synaptophysin established the human SYP locus on the X chromosome in
      subbands Xp11.22-p11.23 and the mouse synaptophysin gene locus (Syp) on the X
      chromosome in region A-D. In addition, an Eco0109 RFLP has been identified and
      used in genetic mapping of the human SYP locus and supports the order TIMP-SYP
      DXS14 within a span of approximately 4-7 centimorgans.

PMID- 1975482
TI  - Hydrophobic stripping voltammetry of antihypertensive drugs at lipid-modified
      electrodes.
AB  - The antihypertensive agents reserpine and rescinnamine were shown to be
      partitioned effectively into a lipid layer on a glassy carbon electrode. Such
      hydrophobic accumulation greatly enhances the sensitivity of the subsequent
      voltammetric scan, allowing convenient quantification of sub-micromolar
      concentrations. A high degree of selectivity is achieved as polar electroactive
      species are excluded by the hydrophobic layer. The drugs can therefore be
      quantified in the presence of a 100-fold amount of solution species with similar
      redox potentials. The response was evaluated with respect to accumulation time,
      concentration dependence, solution conditions, voltammetric waveform, possible
      interferences and other variables. Detection limits are 5 x 10(-9) M. The
      applicability of the method to selective measurements in untreated urine is
      described. The data shed new light on the sensing utility and discriminative
      properties of lipid electrodes.

PMID- 1975483
TI  - Test doses: optimal epinephrine content with and without acute beta-adrenergic
      blockade.
AB  - The authors studied the optimal epinephrine content of an epidural test dose, and
      determined criteria to identify intravascular injections in subjects with or
      without beta-adrenergic blockade. Nine healthy nonpregnant subjects 25-36 years
      of age were given intravenous infusions of saline or esmolol in random order.
      During each infusion, they received a series of five injections (3 ml each) of
      either saline, 1% lidocaine or 1% lidocaine containing 5, 10, or 15 micrograms of
      epinephrine. Thirty minutes after completing these two infusions, propranolol was
      administered as a bolus injection, and the series of five injections repeated.
      All injections were double blind and randomized. During saline infusion, all
      injections containing epinephrine significantly increased heart rate (HR) by an
      average of 31-38 beats/min when compared with that following plain lidocaine (P
      less than 0.05), and increased systolic blood pressure by an average of 17-26
      mmHg (P less than 0.05 for the 15-micrograms dose only). During esmolol infusion,
      epinephrine injections increased HR by an average of 23-31 beats/min (P less than
      0.05), and increased systolic blood pressure by an average of 18-30 mmHg (P less
      than 0.05 for 10 and 15 micrograms). After propranolol injection, epinephrine
      injections caused a decrease in HR by an average of 21-28 beats/min (P less than
      0.05), whereas systolic blood pressure increased by an average of 22-35 mmHg (P
      less than 0.05 for 10 and 15 micrograms only). Without beta-adrenergic blockade,
      an increase in HR greater than or equal to 20 beats/min was 100% sensitive and
      specific for intravascular injection of 10 or 15 micrograms of
      epinephrine.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1975484
TI  - Can early administration of neostigmine, in single or repeated doses, alter the
      course of neuromuscular recovery from a vecuronium-induced neuromuscular
      blockade?
AB  - The authors sought to determine whether neostigmine, given at a time when no
      response to peripheral nerve stimulation could be elicited, hastened recovery
      from a vecuronium-induced neuromuscular blockade (NMB). The effect of neostigmine
      (70 micrograms/kg) in antagonizing a profound (no-twitch) vecuronium-induced (0.1
      mg/kg) NMB in 40 healthy patients was studied. Patients were randomly assigned to
      one of four groups specifying the sequence of neostigmine administration. Fifteen
      minutes after the administration of vecuronium, when there was no detectable
      twitch response, each patient received either neostigmine (70 micrograms/kg) with
      glycopyrrolate (15 micrograms/kg) or an equivalent volume of normal saline
      (placebo). When T1 (the first response in the train-of-four [TOF] sequence)
      recovered to 10% of control, patients again received either neostigmine with
      glycopyrrolate in the same doses as before or the placebo. The following
      variables were measured: times from vecuronium injection until T1 recovered to
      10% (t [10]) and 90% (t [90]) of control, and time until the TOF ratio was equal
      to 75% (t [TOF75]). Mean values of t (90) and t (TOF75) were shorter (54.7-75.2
      min and 60.4-79.5 min, respectively) for the three groups who received
      neostigmine as compared with patients who received two doses of placebo (104.3
      and 122.6 min, respectively). There were no differences in the t (90) and t
      (TOF75) values among the three groups who received neostigmine.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1975485
TI  - Comparative effects of esmolol and verapamil in a model of a supraventricular
      tachydysrhythmia.
AB  - Supraventricular tachydysrhythmias are a commonly encountered clinical problem
      after cardiothoracic surgery. Current choices for acute drug therapy of these
      dysrhythmias include intravenous verapamil as well as esmolol, but no data yet
      exist comparing the relative negative dromotropic (atrioventricular [A-V] nodal
      blocking) and negative inotropic effects of these agents. The purpose of this
      study was to compare the effects of esmolol with those of verapamil on systemic
      hemodynamics, coronary blood flow, and cardiac contractility at doses that
      produce a similar ventricular response rate in an animal model of a
      supraventricular tachydysrhythmia. Rapid electrical stimulation (800
      impulses/min) of the left atrium in 14 dogs resulted in a rapid and irregularly
      irregular ventricular rhythm. Esmolol or verapamil were administered by bolus and
      then infusion to incrementally slow the average ventricular rate. Regional
      myocardial contractility was measured using the end-systolic pressure-length
      relationship (Ees). At drug doses that produced similar decreases in ventricular
      rate, esmolol produced a greater decrease in contractility (Ees: 284 +/- 46 to 40
      +/- 22 mmHg/mm, LV dp/dt: 2,400 +/- 450 to 1,360 +/- 450 mmHg/sec) compared with
      that following verapamil (Ees: 297 +/- 57 to 116 +/- 25 mmHg/mm, LV dp/dt: 2,040
      +/- 580 to 1,950 +/- 520 mmHg/sec). This was accompanied by a modest decrease in
      cardiac output in the esmolol group (2,800 +/- 940 to 2,290 +/- 730 ml/min)
      compared with an unchanged cardiac output as ventricular rate slowed in verapamil
      treated animals. Stroke volume increased significantly in the verapamil-treated
      animals (10.9 +/- 4.0 to 18.5 +/- 4.6 ml), but remained unchanged following
      esmolol.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1975486
TI  - Myopathy with human immunodeficiency virus type 1 (HIV-1) infection: HIV-1 or
      zidovudine?

PMID- 1975487
TI  - Syngeneic bone marrow transplantation and adoptive transfer of peripheral blood
      lymphocytes combined with zidovudine in human immunodeficiency virus (HIV)
      infection.
AB  - OBJECTIVE: To examine the role of syngeneic bone marrow transplantation and
      peripheral blood lymphocyte infusions combined with zidovudine in the treatment
      of patients with human immunodeficiency virus (HIV) infection. DESIGN: A
      partially randomized outpatient trial. SETTING: Outpatient and inpatient facility
      of the Clinical Center of the National Institutes of Health, a research-based
      referral facility. PATIENTS: Sixteen patients with HIV infection (15 symptomatic,
      1 asymptomatic). INTERVENTIONS: Symptomatic patients were treated with
      zidovudine, 500 mg orally every 4 hours for 12 weeks, combined with six
      peripheral blood lymphocyte infusions (four at week 10, two at week 12) and bone
      marrow transplantation (at week 12) using HIV-seronegative identical twins as
      donors. After transplantation, patients were randomly assigned to receive either
      zidovudine, 100 mg every 4 hours, or placebo for 12 months. The asymptomatic
      patient received zidovudine for the first 12 weeks, discontinuing therapy after
      transplantation. Immunologic and virologic monitoring were done monthly.
      MEASUREMENTS AND MAIN RESULTS: Immediately after lymphocyte infusions and bone
      marrow transplantation, there was an increase in the mean (+/- SE) CD4 cell
      percent (19.1% +/- 3.1% to 28.1% +/- 3.0%), an increase in the fraction of
      patients with delayed-type hypersensitivity responses to tetanus toxoid (4 of 13
      to 11 of 13) and the development of delayed-type hypersensitivity to keyhole
      limpet hemocyanin (a primary immunogen to which only the donor had been
      immunized) in 8 of 12 patients tested. No significant clinical improvement was
      noted, however, and there was no overall sustained immunologic improvement. No
      differences in CD4 cell percents, delayed-hypersensitivity skin tests, HIV
      cultures, or p24 antigenemia were seen between patients treated with zidovudine
      or placebo after transplantation. CONCLUSIONS: Although they establish the
      feasibility of combining zidovudine with cellular immune reconstitution in
      treating patients with HIV infection, our results show that any benefits from
      such combination therapy are at best transient. Future attempts at cellular
      immune reconstitution may need to use improved antiretroviral regimens as well as
      immunization of donors with HIV-specific antigens.

PMID- 1975488
TI  - Pharmacogenetic analysis of mechanisms of emotional stress: effects of
      benzodiazepines.
AB  - The effects of the benzodiazepine tranquilizer phenazepam (0.05, 0.075, 0.1
      mg/kg) in the open field test of the mice C57Bl/6, BALB/c strains and their F1
      hybrids have been studied. The tranquillizer produced a dose-dependent
      suppression of the locomotor activity of C57Bl/6 mice, while 0.05 mg/kg activated
      the behaviour of the BALB/c mice. The response to phenazepam of F1 hybrids
      resembled that of their C57Bl/6 parental strain, also in their pattern of the
      open field behaviour. Interstrain differences in the plasmatic levels of ACTH,
      corticosterone, cAMP and cGMP after the open field test have been detected.
      Interstrain differences in the modifications of [3H]-diazepam and [35S]-TBPS
      binding to brain membranes between C57Bl/6 and BALB/c mice, dependent on the -Cl
      ions addition, have been also found.

PMID- 1975489
TI  - Mobilization of the gentamicin resistance gene in Enterococcus faecalis.
AB  - Enterococcus faecalis plasmid pBEM10 (a conjugative plasmid encoding beta
      lactamase production and gentamicin resistance [Gmr]) was made transfer deficient
      by using Tn917. Relocation of the Gmr determinant into two sites on pCF10 was
      observed. Restriction analysis revealed insertion of a common 2.5-kilobase-pair
      HindIII and a 3.9-kilobase-pair HaeIII fragment encoding Gmr, suggesting that
      this determinant resides on a transposon similar to Tn4001.

PMID- 1975490
TI  - Randomized trial of postoperative patient-controlled analgesia vs intramuscular
      narcotics in frail elderly men.
AB  - Postoperative use of as-needed intramuscular narcotics is potentially hazardous
      in frail elderly patients. Patient-controlled analgesia (PCA) allows patients to
      self-administer small boluses of narcotic, allowing better dose titration,
      enhanced responsiveness to variability in narcotic requirements, and reduction in
      serum narcotic level fluctuation. Although theoretically useful, this method has
      not bee well studied in the elderly or medically ill. A prospective controlled
      trial among 83 higher-risk elderly men after major elective surgery compared PCA
      containing morphine sulfate with intramuscular morphine injections as needed
      (mean [+/- SD] age, 67.4 +/- 5.6 vs 67.0 +/- 6.3 years). Subjects had a variety
      of medical illnesses, including chronic lung disease (57%), coronary artery
      disease (43%), heart failure (13%), and liver disease (12%). Preoperative and
      postoperative assessments included chest roentgenograms; daily mental status and
      pulmonary function testing; twice-daily serum morphine levels; and oxygen
      saturation values, linear analogue pain and sedation scores, and vital signs
      every 2 hours. Care was taken to optimize narcotic administration in control
      subjects as well as PCA subjects. Analgesia was significantly improved by PCA (3
      day mean pain score, 40.5 +/- 18.0 vs 32.5 +/- 15.0), without an increase in
      sedation. Significant postoperative confusion (18% vs 2.3%) and severe pulmonary
      complications (10% vs 0%) occurred significantly more frequently in intramuscular
      treated controls. Patient-controlled analgesia was quickly mastered by most
      patients; no major problems referable to its use occurred. Patients who had
      previously received intramuscular injections reported that PCA was easier to use
      and provided better analgesia. Serum morphine levels showed significantly less
      variability on postoperative day 1 with PCA, compared with intramuscular
      injections. We conclude that PCA is an improved method of postoperative analgesia
      in high-risk elderly men with normal mental status, compared with as-needed
      intramuscular injections.

PMID- 1975491
TI  - Mapping of the Hox-3.1 and Myc-1.2 genes on chromosome 15 of the mouse by
      restriction fragment length variations.
AB  - Restriction endonuclease fragment length variations (RFLV) were detected by use
      of the cDNA probe Hox-3.1 for the homeo box-3.1 gene and also the c-myc oncogene
      probe for exon 2. RFLV of Hox-3.1 were found in HindIII restriction patterns, and
      RFLV of the Myc-1.2 gene in EcoRV patterns. From the RFLV, the Hox-3.1 and Myc
      1.2 genes were mapped on chromosome 15. Three-point cross test data showed that
      the frequency of recombination is 26.4% between Myc-1.2 and Gpt-1, 30.2% between
      Gpt-1 and Gdc-1, and 9.4% between Gdc-1 and Hox-3.1. The following order of these
      genes is proposed, Myc-1.2--Gpt-1--Gdc-1--Hox-3.1. All laboratory strains carry
      the Hox-3.1a and Myc-1.2a alleles. Among strains of wild origin, domesticus
      strains carry only the Hox-3.1a and Myc-1.2a alleles, as do the laboratory
      strains. One strain of brevirostris carries the Hox-3.1a and Myc-1.2b alleles.
      Other wild subspecies from Europe and Asia, M. m. musculus, M. m. castaneus, M.
      m. molossinus, Chinese mice of wild origin, and M. m. yamashinai carry the Hox
      3.1b and Myc-1.2b alleles.

PMID- 1975492
TI  - Polymorphisms in the coding and noncoding regions of murine Pgk-1 alleles.
AB  - The mouse X-linked Pgk-1 gene encodes phosphoglycerate kinase. When transfected
      into human cells, the Pgk-1b allele causes the appearance of mouse PGK-1b enzyme
      activity. We describe here cloning of mouse Pgk-1a, an allele of Pgk-1 which
      encodes an enzyme, PGK-1a, with distinct electrophoretic mobility. We constructed
      recombinants between the DNA encoding Pgk-1b and Pgk-1a and transfected these
      constructs into human cells to assess the electrophoretic characteristics of each
      recombinant. In this way the charge variation between the two proteins was
      localized to exons 4 or 5. Sequencing of these exons revealed a single base-pair
      difference between the two alleles at codon 155, which predicts the amino acids
      lysine and threonine in PGK-1b and PGK-1a, respectively. A number of other DNA
      sequence polymorphisms exist between Pgk-1b and Pgk-1a including part of an L1
      repeated element unique to Pgk-1a.

PMID- 1975493
TI  - Perspectives on methylmalonic acidemia resulting from molecular cloning of
      methylmalonyl CoA mutase.
AB  - Methylmalonyl CoA mutase deficiency (methylmalonic acidemia) has been a paradigm
      for biochemical and somatic cell genetic approaches to human disease. Recently,
      genes encoding this enzyme have been cloned from several species. These studies
      have provided information about the primary structure and evolution of this
      enzyme, the mutations which underlie its deficiency state, and the structure
      function determinants which are required for its activity. Gene transfer studies
      now permit restitution of this enzyme to genetically deficient cells and may
      enable somatic gene therapy to be undertaken. Molecular genetic studies not only
      provide more detailed information about this enzyme, but introduce new
      perspectives on the molecular mechanisms and dynamics of its function and raise
      new questions about the dyshomeostatic consequences of its deficiency.

PMID- 1975494
TI  - Molecular evolution and zinc ion binding motif of leukotriene A4 hydrolase.
AB  - Leukotriene A4 (LTA4) hydrolase belongs to the aminopeptidase N family. In order
      to investigate the molecular evolution and physiological significance of LTA4
      hydrolase, the enzymes belonging to the family were aligned and a phylogenetic
      tree was constructed. From the alignment, it was found that three residues
      involved in zinc binding and one residue of the active sites of aminopeptidases N
      were conserved in LTA4 hydrolase. In agreement with the observation, LTA4
      hydrolase is a zinc protein as determined by atomic absorption spectroscopy.

PMID- 1975495
TI  - Crystallization and preliminary X-ray diffraction studies of the engrailed
      homeodomain and of an engrailed homeodomain/DNA complex.
AB  - The homeodomain from the engrailed protein of Drosophila has been crystallized
      from ammonium phosphate at pH 6.8. The crystals form in space group P6(1)22 (or
      P6(5)22), with cell dimensions a = b = 44.8 A and c = 118.2 A. These crystals
      diffract to 1.8 A resolution. A complex containing the engrailed homeodomain and
      a duplex DNA site also has been crystallized. The cocrystals form in space group
      C2 with a = 131.2 A, b = 45.5 A, c = 72.9 A and beta = 119.0 degrees. These
      crystals diffract to 2.6 A resolution.

PMID- 1975496
TI  - A study on CNS-side effects of mequitazine, an H1-specific antihistamine in
      healthy Thai volunteers.
AB  - Mequitazine is a potent, non-sedative, long-acting H1-specific antihistamine
      proven to be a better therapeutic drug than other conventional antihistamines. It
      is also reported by many authors that the drug produces less sedative or other
      depressive actions on the central nervous system than other antihistamines. In
      order to evaluate the advantage of this drug in Asian people, an assessment of
      side effects of mequitazine, in comparison with chlorpheniramine, on the central
      nervous system was done in 20 healthy Thai volunteers, 10 males and 10 females 23
      39 years of age, using a double blind crossover placebo controlled trial. Various
      subjective tests: alertness scale rating, visual analogue scale rating as well as
      objective tests: card sorting, glassbead picking and estimation of reaction time,
      were performed. There were no significant differences in side effects on the
      central nervous system between mequitazine and the placebo, whereas
      chlorpheniramine did produce side effects.

PMID- 1975497
TI  - [Biologico-periodontal considerations in restoration of teeth partially destroyed
      by caries or traumatism].
AB  - Since a great number of teeth could be rehabilitated and not extracted, in this
      paper we analyze the relation Perio-protesis by the point of the biology of
      marginal periodontal ligament, and the different options to establish this
      relations when are lost by decay or traumatism. We discuss the contraindications
      to avoid greater problems than benefits when intend to rehabilitate lost teeth.

PMID- 1975498
TI  - [External inflammatory root resorption].

PMID- 1975499
TI  - Dendrobine support studies. The structure of a novel 3-azatricyclo[6.2.1.0(4,11)]
      undecane derivative.
AB  - (1S*, 4R*, 8S*, 11R*)-3-Diphenylmethyl-11-methyl-3-
      azatricyclo[6.2.1.0(4,11)]undec-5-en-2-one, C24H25NO, Mr = 343.47, monoclinic,
      P2(1), a = 10.248 (3), b = 8.859 (2), c = 10.344 (2) A, beta = 99.816 (14)
      degrees, V = 925.4 (3) A3, Z = 2, D chi = 1.23 g cm-1 (163 K), lambda(Mo K alpha)
      = 0.7107 A, mu = 0.6927 cm-1, F(000) = 368, T = 163 K, R = 0.0423 for 2569
      reflections. The compound is spontaneously resolved upon crystallization. The N
      atom appears to be sp2 hybridized [N is 0.0901 (13) A from plane through three
      ligand atoms] and in conjugation with the carbonyl group [short N--C bond 1.351
      (2) A]. The tricyclic ring system is concave. Ring strain appears to affect C--C
      bond lengths of the central atom of the 3-ring system. The average C--C bond
      length for this atom to other ring atoms is 1.551 (2) while the average for all
      other sp3 C--sp3 C bonds is 1.530 (2) A.

PMID- 1975500
TI  - Sudden death as sole symptom of coronary arteritis.
AB  - A 33-year old man suddenly dropped dead during a military march. He had
      complained of non-specific thoracoabdominal symptoms, pain and fatigue for a year
      before his death. Autopsy showed coronary polyarteritis nodosa of the left main
      coronary artery. This patient seems to be only the second case with isolated
      polyarteritis nodosa leading to sudden death reported in the literature.

PMID- 1975501
TI  - [Laser destruction of a broncholith of the middle-lobe bronchus].

PMID- 1975502
TI  - 9-Alkyl, morpholinyl anthracyclines in the circumvention of multidrug resistance.
AB  - The intramolecular combination of 9-alkyl substitution in the anthracycline A
      ring plus incorporation of the amino group of the daunosamine sugar within a
      morpholinyl ring led to the retention of almost complete activity against P
      glycoprotein positive, multidrug resistant variants of a mouse mammary tumour
      line and a human small cell lung cancer line. Resistance factors were close to
      unity. These structural elements may prevent efflux by the P-glycoprotein
      multidrug transporter. The use of 9-alkyl, morpholinyl anthracyclines with
      resistance circumvention properties may have clinical application.

PMID- 1975503
TI  - Disease-modifying antirheumatic drugs: gold, penicillamine, antimalarials, and
      sulfasalazine.

PMID- 1975504
TI  - Genes and mechanisms involved in early embryonic development in Xenopus laevis.
AB  - Our laboratory is studying genes involved in the regulation of the balance
      between cell growth and differentiation during embryonic development in Xenopus.
      We have analyzed the developmental expression of the proto-oncogenes c-myc, and
      KiRas 2B, the proliferating cell nuclear antigen (PCNA), and the tumor suppressor
      gene p53. These genes, usually expressed during cell proliferation, are expressed
      in the oocyte in large quantities, but the majority of their maternal RNAs are
      degraded by the gastrula stage. The expression of c-myc and the localization of
      the protein indicate that c-myc has the characteristics expected for a gene
      involved in the regulation of the mid-blastula transition, when zygotic
      expression is turned on in the embryo. Its expression during late development or
      during regeneration indicates that it enables the cells to remain competent for
      cycling during organogenesis. In vitro systems that reproduce the principal
      cellular functions during early development are used as model systems to
      understand the mechanisms involved in early embryogenesis.

PMID- 1975505
TI  - Proliferating cell nuclear antigen expression in childhood acute leukemia.
AB  - Proliferating cell nuclear antigen (PCNA) is a 36-Kd nuclear protein, identified
      as the auxiliary protein of DNA polymerase delta, that is upregulated in
      activated proliferating cells from a variety of tissues and species, including
      human lymphocytes. We have examined by two-dimensional polyacrylamide gel
      electrophoresis the expression of PCNA in various subtypes of childhood acute
      leukemia and have found differences in its expression according to subtype. These
      differences were not related to the initial peripheral white blood count, age, or
      sex, and appeared to reflect differences in proliferative activity between
      subtypes of acute leukemia.

PMID- 1975506
TI  - Demonstration of immunoreactive vasoactive intestinal peptide (IR-VIP) and
      somatostatin (IR-SOM) in rat thymus.
AB  - In the present work we demonstrate immunohistochemically the presence of both
      immunoreactive vasoactive intestinal peptide (IR-VIP) and immunoreactive
      somatostatin (IR-SOM) cells in the thymus of neonatal and adult rats. IR-VIP and
      IR-SOM from thymic tissue extracts were identified by gel chromatography, HPLC as
      VIP standard, and somatostatin S-28, respectively. IR-VIP (352.7 pg/thymus)
      amounts greater than those of IR-SOM (38.7 pg/thymus) detected by
      radioimmunoassay in the thymus of 3-month-old rats reflected the abundance of IR
      VIP positive cells demonstrated by immunohistochemistry. Somatostatin-like
      immunoreactive cells were identified as epithelial or neuroendocrine-like cells
      arranged in the thymic cortico-medullary border, whereas IR-VIP positive cells
      appeared to be large lymphoid cells distributed along the connective tissue
      trabeculae. Furthermore, IR-VIP lymphoid cells occurred in the periarteriolar
      lymphoid tissue of the splenic white pulp where lymphoblasts accumulate. The
      results are discussed with respect to the mutual interactions between the
      neuroendocrine and immune systems and the possible role played by neuropeptides
      in these interactions.

PMID- 1975507
TI  - Effect of corticosteroid creams on descent of testes in infants. John Radcliffe
      Hospital Cryptorchidism Study Group.

PMID- 1975508
TI  - Towards a more rapid diagnosis of rapidly progressive glomerulonephritis.
AB  - An attempt was made to provide simple practical guidelines to alert general
      practitioners to the diagnosis of rapidly progressive glomerulonephritis and lead
      to early referral to hospital. The duration of illness before referral to this
      hospital and its effect on outcome in patients with crescentic nephritis were
      assessed retrospectively from the case notes of 24 patients referred over two
      years. Four patients had Goodpasture's syndrome, 11 Wegener's granulomatosis,
      seven microscopic polyarteritis, and two idiopathic progressive
      glomerulonephritis. The duration of symptoms before referral to the local
      hospital was similar in the four groups of patients and varied from one week to
      28 months (mean 10 months). The duration of stay in the local hospital was two,
      nine, 11, and 180 days in the patients with Goodpasture's syndrome and a mean of
      four days (range one to eight) in those with Wegener's granulomatosis and 10 days
      (one to 18 days) in those with microscopic polyarteritis. In the local hospital
      the diagnosis was based on the results of renal biopsy and detection of
      antibodies to glomerular basement membrane in two patients with Goodpasture's
      syndrome and on the results of renal biopsy in seven of the other patients aided
      by the detection of antibodies to the cytoplasm of neutrophils (ANCA) in 10.
      Three of the 24 patients died and four required maintenance haemodialysis.
      Patients who present to their general practitioners with persistent non-specific
      symptoms should have a urine dipstick test and then blood tests and emergency
      referral to hospital if necessary. Hospital physicians should be aware of the
      speed and accuracy with which current assays can confirm a diagnosis of rapidly
      progressive glomerulonephritis.

PMID- 1975509
TI  - The salvage of rabbit ischaemic epigastric free flaps using the vasodilator
      calcitonin gene-related peptide.
AB  - The rabbit epigastric free flap, subjected to 21 hours of warm (25 degrees C)
      ischaemia, was used as an experimental model to test the ability of two
      endothelium-dependent vasodilators, calcitonin gene-related peptide (CGRP) and
      carbamyl beta-methylcholine chloride (MCh, bethanechol chloride, the stable
      acetylcholine analogue) to improve flap viability. After the period of ischaemia,
      flaps were infused intra-arterially with either Hanks balanced salt solution
      (controls), CGRP or MCh for 30 minutes, and received additional intravenous
      boluses of these drugs at 2 and 32 minutes after revascularisation. The area of
      flap surviving improved significantly (p less than 0.025) from 39.9% (n = 18) for
      controls to 70.2% (n = 14) for CGRP treatment at 2 micrograms/kg, but was
      unchanged at 47.1% (n = 14) for MCh treatment at 50 micrograms/kg. Both CGRP and
      MCh significantly increased blood flow (p less than 0.05) resulting in 34% lower
      peripheral resistances compared with controls. These results suggest that CGRP
      has considerable clinical potential for the salvage of ischaemic flaps. CGRP must
      have several, as yet undefined, beneficial effects on the ischaemic tissue, since
      MCh invoked a vasodilatory response but failed to salvage ischaemic flaps.

PMID- 1975510
TI  - Allelotype of human malignant astrocytoma.
AB  - Astrocytoma, the most common brain tumor in humans, is usually malignant and
      virtually incurable. Two types of malignant astrocytomas can be distinguished
      histopathologically: anaplastic astrocytoma and glioblastoma multiforme. Studies
      using DNA markers that detect restriction fragment length polymorphisms have
      shown that loci on chromosomes 10 and 17p are lost frequently in tumor DNA from
      malignant astrocytoma patients, suggesting that tumor suppressor genes important
      in astrocytoma tumorigenesis may be present on 2 different chromosomes. To
      identify additional regions of chromosome loss, we carried out an allelotype
      analysis of 41 malignant astrocytoma patients using restriction fragment length
      polymorphism markers for each arm of every human autosome. Loss of heterozygosity
      was found for every autosome except chromosome 21, indicating an even greater
      complexity of genomic alterations than reported previously. Many tumors showed
      loss of heterozygosity for multiple chromosomes and the number of chromosomes
      involved correlated with tumor histopathology. A high-resolution restriction
      fragment length polymorphism study of chromosome 10 loci in these patients showed
      that loss of broad regions of chromosome 10 was a common event, particularly in
      glioblastoma multiforme. An allelotype analysis has been carried out on only one
      other tumor, human colorectal carcinoma. Different profiles of allele loss were
      observed in malignant astrocytoma and colorectal carcinoma, suggesting that the
      genetic events leading to these 2 human cancers may proceed along different
      pathways.

PMID- 1975511
TI  - Analysis of the int-1, int-2, c-myc, and neu oncogenes in human breast
      carcinomas.
AB  - We have examined the DNA obtained from 100 primary breast carcinomas for oncogene
      markers which might have predictive value for poor prognosis. Ninety-six of the
      tumors were analyzed for the presence of restriction fragment length
      polymorphisms (RFLPs) previously identified in the int-2 gene. An 8.4-kilobase
      BamHI fragment and a 3.9-kilobase PstI fragment specific for the int-2 gene, in
      the absence of other restriction fragments, was found in 17 of 50 (34%) lymph
      node-negative patients and in 27 of 44 (61%) lymph node-positive patients. This
      combination of int-2 RFLPs (8.4/3.9) was found in a significantly different
      proportion (P = 0.02) of patients with greater than 3 positive lymph nodes
      compared to patients with fewer positive lymph nodes, suggesting that these RFLPs
      may be valuable for distinguishing among node-negative patients for chemotherapy.
      In contrast, the observed low frequency of int-1, int-2, neu, and c-myc
      amplification limited their usefulness as clinical predictors of disease
      recurrence.

PMID- 1975512
TI  - Human tumor cell line resistance to chemotherapeutic agents does not predict
      resistance to natural killer or lymphokine-activated killer cell-mediated
      cytolysis.
AB  - Cancer cells selected for resistance to natural product chemotherapeutic agents
      typically display cross-resistance to a variety of structurally and
      mechanistically diverse agents, a phenomenon known as multidrug resistance.
      Preliminary studies involving cells selected for multidrug resistance in vitro
      have suggested that the development of resistance to these agents might
      simultaneously confer resistance to some forms of immunotherapy. Using human
      tumor cell line models, we have investigated the relationship between either
      intrinsic or selected multidrug resistance and sensitivity to natural killer (NK)
      or lymphokine-activated killer (LAK) cell-mediated cytolysis. We compared the NK
      and LAK cell susceptibility of three human tumor cell lines displaying distinct
      mechanisms of selected drug resistance with that of the parental drug-sensitive
      lines. We also evaluated the NK and LAK susceptibility of five established renal
      cell carcinoma lines, all of which were found to be intrinsically resistant to
      doxorubicin and vinblastine. The drug-resistant cell lines were variably
      sensitive to NK-mediated lysis. In contrast, all drug-resistant cell lines tested
      were LAK cell sensitive. The NK and LAK cell-mediated cytolytic sensitivities of
      the drug-resistant cell lines correlated well with those of the drug-sensitive
      parental lines, suggesting that susceptibility to lysis was related intrinsically
      to each tumor type, and not to the resistance phenotype. We attempted to
      correlated the NK sensitivity of these cells with the cell surface expression of
      Class I or II histocompatibility antigens, or the presence or absence of the
      membrane inhibitor of complement-mediated reactive lysis. None of these
      phenotypic markers were found to predict NK resistance. We therefore conclude
      that these cells, which are either spontaneously resistant to commonly utilized
      antitumor agents or are multidrug resistant as a result of drug exposure in
      vitro, remain sensitive to LAK cell-mediated cytolysis. Our studies suggest that
      interleukin 2-induced LAK cells may be useful in the therapy of some chemotherapy
      resistant cancers.

PMID- 1975513
TI  - Isolation and characterization of a spontaneously immortalized human breast
      epithelial cell line, MCF-10.
AB  - Two sublines of a breast epithelial cell culture, MCF-10, derived from human
      fibrocystic mammary tissue exhibit immortality after extended cultivation in low
      calcium concentrations (0.03-0.06 mM) and floating transfers in low calcium (MCF
      10F), or by trypsin-Versene passages in the customary (normal) calcium levels,
      1.05 mM (MCF-10A). Both sublines have been maintained as separate entities after
      2.3 years (849 days) in vitro and at present have been in culture for longer than
      4 years. MCF-10 has the characteristics of normal breast epithelium by the
      following criteria: (a) lack of tumorigenicity in nude mice; (b) three
      dimensional growth in collagen; (c) growth in culture that is controlled by
      hormones and growth factors; (d) lack of anchorage-independent growth; and (e)
      dome formation in confluent cultures. Cytogenetic analysis prior to
      immortalization showed normal diploid cells; although later passages showed
      minimal rearrangement and near-diploidy, the immortal cells were not
      karyotypically normal. The emergence of an immortal culture in normal calcium
      media was not an inherent characteristic of the original tissue from which MCF-10
      was derived since reactivated cryo-preserved cells from cultures grown for 0.3
      and 1.2 years in low calcium were incapable of sustained growth in normal
      calcium.

PMID- 1975514
TI  - Membrane vesicle formation due to acquired mitoxantrone resistance in human
      gastric carcinoma cell line EPG85-257.
AB  - A newly established gastric carcinoma cell line (EPG85-257P) exhibited a high
      sensitivity to mitoxantrone (DHAD) as determined by a monolayer proliferation
      assay. The concentration to inhibit cell growth to 50% of controls (IC50) was
      0.0022 micrograms/ml culture medium. The cells were continuously incubated for
      more than 4 months in the presence of stepwise increased concentrations of DHAD,
      and the IC50 was increased to 0.41 micrograms/ml, i.e., 186.4-fold. This
      resistant variant was named EPG85-257RNOV. The EPG85-257RNOV cells became cross
      resistant to Adriamycin with enhanced IC50 by 10.5-fold and to daunomycin with
      enhanced IC50 by 3.9-fold. No distinct resistance was observed to vinblastine,
      vincristine, and colchicine. Verapamil (10(-6), 4 X 10(-6) and 10(-5) M) and
      cyclosporin A (10(-6), 3 X 10(-6) and 10(-5) M) did not reverse DHAD resistance.
      As shown by immunocytochemistry (monoclonal antibodies: C219 and JSB-1) and
      Northern blot analysis, DHAD resistance was not associated with the appearance of
      the multidrug resistance (MDR)-associated (Mr 170,000) P-glycoprotein or the
      overexpression of P-glycoprotein mRNA. The data indicate a chemoresistance
      pattern unlike typical MDR (often called "atypical" MDR). The phenotypes of
      parent and resistant EPG85-257 cells were compared using interference contrast
      microscopy, electron microscopy, and immunocytochemistry. After DHAD application
      the following structural characteristics were found to be associated with
      emergence of resistance: (a) intensive formation of surface vesicles in the
      resistant variant. Such vesicles were almost absent in sensitive cells; (b) the
      vesicles contained the selecting DHAD which was visualized by its blue color; and
      (c) in electron microscopy the vesicles were formed by an inner and an outer
      double membrane, presumably derived from the plasmalemma. These observations
      suggest a complex cellular mechanism responsible for DHAD resistance which
      includes formation of membrane vesicles, vesicular drug binding, and drug
      compartmentalization.

PMID- 1975515
TI  - A developmental switch in thymic lymphocyte maturation potential occurs at the
      level of hematopoietic stem cells.
AB  - Hematopoietic stem cells (HSCs) isolated from mouse fetal liver, like adult HSCs,
      are Thy-1lo Lin- Sca-1+. Donor-derived V gamma 3+ T cells were detected in fetal
      thymic lobes repopulated in vitro with fetal liver HSCs, but not in those with
      adult bone marrow HSCs. Single clonogenic fetal HSCs gave rise to thymic progeny
      that include V gamma 3+, other gamma delta+, and alpha beta+ T cells. No V gamma
      3+ T cells were detected in adult thymus injected intrathymically with either
      fetal or adult HSCs. These results support the hypothesis that only fetal HSCs
      have the capacity to differentiate into V gamma 3+ T cells in the fetal thymic
      microenvironment and that the developmental potential of HSCs may change during
      ontogeny.

PMID- 1975516
TI  - Uncoating protein (hsc70) binds a conformationally labile domain of clathrin
      light chain LCa to stimulate ATP hydrolysis.
AB  - Uncoating of clathrin-coated vesicles is mediated by the heat shock cognate
      protein, hsc70, and requires clathrin light chains (LCa and LCb) and ATP
      hydrolysis. We demonstrate that purified light chains and synthetic peptides
      derived from their sequences bind hsc70 to stimulate ATP hydrolysis. LCa is more
      effective than LCb in stimulating hsc70 ATPase and in inhibiting clathrin
      uncoating by hsc70. These differences correlate with high sequence divergence in
      the proline- and glycine-rich region (residues 47-71) that forms the hsc70
      binding site. For LCa, but not LCb, this region undergoes reversible
      conformational changes upon perturbation of the ionic strength or the calcium ion
      concentration. Our results show that LCa is more important for interactions with
      hsc70 than is LCb and suggest a model in which the LCa conformation regulates
      coated vesicle uncoating.

PMID- 1975517
TI  - A molecular basis for familial hypertrophic cardiomyopathy: a beta cardiac myosin
      heavy chain gene missense mutation.
AB  - A point mutation in exon 13 of the beta cardiac myosin heavy chain (MHC) gene is
      present in all individuals affected with familial hypertrophic cardiomyopathy
      (FHC) from a large kindred. This missense mutation converts a highly conserved
      arginine residue (Arg-403) to a glutamine. Affected individuals from an unrelated
      family lack this missense mutation, but instead have an alpha/beta cardiac MHC
      hybrid gene. Identification of two unique mutations within cardiac MHC genes in
      all individuals with FHC from two unrelated families demonstrates that defects in
      the cardiac MHC genes can cause this disease. The pathology resulting from a
      missense mutation at residue 403 further suggests that a critical function of
      myosin is disrupted by this mutation.

PMID- 1975518
TI  - Specific role of an alpha,beta-unsaturated carbonyl group in gamma
      glutamylcysteine synthetase induction by prostaglandin A2.
AB  - The effects of prostaglandins (PGs) on cellular glutathione (GSH) status in L
      1210 cells were examined. PGA2 and J2, which have an alpha,beta-unsaturated
      carbonyl group in the cyclopentane ring, elevated the GSH content, but PGB2, D2,
      E2 and F2 alpha did not show the effect. When L-1210 cells were incubated with
      various 2-cyclopentenone derivatives, 4-hydroxy-2-cyclopentenone and some of
      related compounds elevated cellular GSH levels. Subsequent study with cell-free
      extract of cultured L-1210 cells revealed that PGA2 and 4-hydroxy-2
      cyclopentenone induced gamma-glutamycysteine synthetase activity at the
      transcriptional level. This induction was also found in other cultured mammalian
      cells such as HeLa S3, NIH/3T3 and porcine aorta endothelial cells. When L-1210
      cells were incubated with PGA2 in the presence of 4-hydroxy-2-cyclopentenone and
      its analogues, they inhibited the accumulation of PGA2 in cell nuclei. Our
      findings thus suggest that an alpha,beta-unsaturated carbonyl moiety is
      responsible for enhancing the biosynthesis of gamma-glutamylcysteine synthetase
      in cultured cells.

PMID- 1975519
TI  - Design and synthesis of an opioid receptor probe: mode of binding of S-activated
      (-)-6 beta-sulfhydryldihydromorphine with the SH group in the mu-opioid receptor.

PMID- 1975520
TI  - Altered cardiovascular and neurohumoral responses to head-up tilt after heart
      lung transplantation.
AB  - Heart-lung transplantation results in afferent and efferent denervation of the
      transplanted organs including interruption of the central connections from the
      low-pressure receptors in the atria and pulmonary veins. We investigated whether
      the cardiovascular and neurohumoral responses to the postural stimulus of head-up
      tilt were affected after transplantation. Responses in eight heart-lung
      transplant recipients were studied and compared with those in eight normal
      subjects matched for age and sex during passive head-up tilt at 45 degrees for 1
      hour. The transplant group had a higher initial heart rate (99 +/- 2 versus 68 +/
      2 beats/min, p less than 0.001) and diastolic blood pressure (88 +/- 5 versus 76
      +/- 2 mm Hg, p less than 0.05) than did the control group. The increases in heart
      rate and diastolic blood pressure during head-up tilt were similar in the two
      groups. Systolic blood pressure remained unchanged. The decrease in cardiac
      output (30% versus 18%, p less than 0.05) and the increase in systemic vascular
      resistance (52% versus 28%, p less than 0.05) were greater in the transplant
      group. Baseline levels of norepinephrine, epinephrine, vasopressin, and plasma
      renin activity were similar in the two groups. Atrial natriuretic peptide
      concentrations were higher in the transplant group (26 +/- 3.8 versus 9.7 +/- 1.6
      pmol/l, p less than 0.001). During head-up tilt, plasma norepinephrine levels
      increased to a greater extent in the transplant group than in the control group
      (83% versus 53%, p less than 0.01), indicating an increased sympathetic response.
      In contrast, plasma renin activity increased significantly in the control group
      but not in the transplant group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1975521
TI  - Incidence of sudden cardiac death associated with coronary artery occlusion in
      dogs with hypertension and left ventricular hypertrophy is reduced by chronic
      beta-adrenergic blockade.
AB  - Because beta-adrenergic blockade has as one of its many effects altered
      electrophysiological abnormalities after dogs with left ventricular hypertrophy
      have been subjected to coronary occlusion, we tested the hypothesis that
      metoprolol (200-400 mg/day) would reduce mortality rates in dogs with one-kidney,
      one clip left ventricular hypertrophy while a similar reduction in arterial
      pressure with enalapril (20-40 mg/day) would not. Dogs with left ventricular
      hypertrophy were given metoprolol or enalapril for 5-7 days before a 3-hour
      coronary occlusion. Infarct size and risk area were measured with
      triphenyltetrazolium chloride stain and barium angiography, respectively. For
      control (n = 15), left ventricular hypertrophy (n = 17), left ventricular
      hypertrophy plus metoprolol (n = 12), and left ventricular hypertrophy plus
      enalapril (n = 15) groups, mean arterial pressure, ratio of infarct size to risk
      area, and dogs experiencing sudden death were 110 +/- 4, 142 +/- 4, 121 +/- 7,
      and 120 +/- 3 mm Hg; 44 +/- 5%, 65 +/- 5%, 44 +/- 7%, and 30 +/- 4%; and 27%,
      65%, 17%, and 53%, respectively. Thus, the excessive increase in early mortality
      occurring when dogs with hypertension and left ventricular hypertrophy undergo
      coronary occlusion is interrupted with beta-blockade, possibly via
      electrophysiological effects rather than by changes in arterial pressure or
      infarct size.

PMID- 1975522
TI  - Routine medical management of acute myocardial infarction. Lessons from overviews
      of recent randomized controlled trials.
AB  - In recent years, several large randomized trials have clarified the role of
      various interventions in acute myocardial infarction. There is clear evidence
      that thrombolytic therapy, aspirin, and beta-blockers reduce mortality. Both
      aspirin and beta-blockers also reduce reinfarction and stroke. Of the
      thrombolytic agents, comparative trials have established that tissue plasminogen
      activator and streptokinase have similar effects on mortality, morbidity, and
      left ventricular function. There appears to be an increased risk of cerebral
      hemorrhage with tissue plasminogen activator. The benefits of heparin in
      conjunction with aspirin and a thrombolytic agent are unclear and, at best, are
      likely to be modest. Heparin increases the risk of hemorrhagic complications
      twofold. Although trials of vasodilators conducted before the widespread use of
      thrombolytic therapy and aspirin have been promising, newer trials are needed to
      evaluate their effects among patients receiving these agents. The aggregate of
      all trials of the routine use of calcium antagonists or antiarrhythmic agents
      indicates that these agents do not improve survival.

PMID- 1975523
TI  - Alterations in beta-adrenergic receptors, adenylate cyclase, and cyclic AMP
      concentrations during acute myocardial ischemia and reperfusion.
AB  - Acute severe myocardial ischemia and evolving myocardial infarction cause neural
      stimulation, increased levels of circulating catecholamines, and release of
      catecholamines from storage depots in the left ventricle, with consequent
      exposure of injured myocardial cells to relatively high concentrations of
      catecholamines during the transitional period in which myocyte injury becomes
      progressively more severe. beta-Adrenergic receptor numbers may be increased in
      the ischemic myocardium within 15-35 minutes of coronary artery occlusion and are
      associated with intact or enhanced coupling with the adenylate cyclase enzyme and
      elevated levels of cyclic adenosine monophosphate (AMP); their stimulation may
      mediate ventricular fibrillation. The administration of beta-adrenergic blockers
      before or within the first few minutes after coronary artery occlusion prevents
      or attenuates the development of ventricular fibrillation. beta-Receptor numbers
      are increased in the ischemic myocardium at 60 minutes of coronary artery
      occlusion but are uncoupled from the adenylate cyclase enzyme at the level of the
      G protein and/or catalytic unit. However, with reperfusion after 60 minutes of
      coronary artery occlusion, the increase in ischemic-region beta-adrenergic
      receptor numbers persists, and adenylate cyclase responsiveness to beta-receptor
      stimulation is restored. If a catecholamine is administered, increases in cyclic
      AMP and activated phosphorylase occur in ischemic-reperfused myocardium. These
      data indicate that beta-adrenergic mechanisms may play an important role in
      arrhythmogenesis and may contribute to myocyte injury during severe and intense
      myocardial ischemia and evolving myocardial infarction.

PMID- 1975524
TI  - Beta-blockers, plasma lipids, and coronary heart disease.
AB  - High plasma cholesterol concentration is an important coronary heart disease risk
      factor, particularly in subjects less than 50 years old. Cholesterol is
      transported mainly by low (LDLs) and high (HDLs) density lipoproteins. High
      plasma levels of HDL and its apolipoprotein (A-I) are associated with low
      coronary heart disease risk, and the reverse is true for LDL and its
      apolipoprotein (B). Plasma levels of very low density lipoproteins (VLDLs) are
      probably not an independent risk factor, and the situation for plasma
      triglycerides is unclear. beta-Blockers have no significant effects on plasma
      concentrations of either total or LDL cholesterol, but HDL plasma concentration
      is reduced by about 10%, particularly by nonselective beta-blockers. Plasma
      triglyceride and VLDL concentrations are both raised by beta-blockade. Despite
      these plasma lipid changes, beta-blockers, by decreasing myocardial oxygen
      requirements, exhibit marked anti-ischemic properties. beta-Blockers without
      intrinsic sympathomimetic activity effect a 30% decrease in death from myocardial
      infarction (MI) in the years after an acute MI. Primary prevention of MI by beta
      blockade in hypertensive persons has been well debated and probably exists
      (although to a lesser extent than secondary prevention) in men, particularly for
      nonsmokers (for nonselective beta-blockers), and despite any plasma lipid
      changes. beta-Blockade can inhibit the preatheromatous and atheromatous changes
      induced by catecholamines in the coronary arteries of animals. beta-blockers may
      also reduce or slow the following processes: 1) endothelial permeability to
      lipoproteins; 2) acylcholesterol acyltransferase activity within the arterial
      wall, thereby preventing cholesterol esterification and deposition in foam cells;
      3) LDL precipitation with arterial wall proteoglycans; 4) calcium influx into
      atheromatous areas; 5) preatheromatous increased endothelial turnover; 6) heart
      rate; 7) blood velocity and flow disturbances; 8) atheromatous plaque rupture and
      consequent coronary thrombosis; and 9) platelet activity. Thus, beta-blockers may
      inhibit atheromatous plaque formation and reduce the likelihood of plaque beta
      blockers may inhibit atheromatous plaque formation and reduce the likelihood of
      plaque rupture, clot formation, and coronary thrombosis.

PMID- 1975525
TI  - Role of the sympathetic nervous system in the pathogenesis of chronic stable
      angina. Implications for the mechanism of action of beta-blockers.
AB  - Thirteen patients with chronic stable effort angina underwent continuous
      ambulatory electrocardiographic and intra-arterial blood pressure monitoring
      during normal unrestricted daily activity. Each patient underwent two studies,
      the first while on no treatment and the second while on beta-blocker therapy.
      During the control period, we recorded 182 episodes of transient ST-segment
      depression, of which only 30 were associated with angina, and 43 (24%) were
      apparently caused by increased myocardial oxygen demand. Although the majority of
      ischemic events (139) were not preceded by an increase in either heart rate or
      systolic arterial pressure, most occurred during the daytime when the levels of
      the rate-pressure product were higher. Throughout the day, beta-blockade
      significantly decreased the levels of heart rate and blood pressure and reduced
      the number of ischemic attacks by 56%, particularly if such attacks were not
      caused by increased myocardial demand. The diurnal distribution of ischemic
      events was not significantly affected by beta-blockade, and again, the majority
      were observed during the day, in coincidence with high resting levels of rate
      pressure product. Whatever the behavior of heart rate and blood pressure before
      ischemia, ST-segment depression was invariably associated with a parallel
      increase in these parameters, highly suggestive of cardiac sympathetic nerve
      activation. We conclude that: 1) The majority of ischemic events that occurred in
      patients with stable angina during normal daily activity were apparently not
      precipitated by an excessive increase in myocardial oxygen demand but rather by
      transient impairment of regional myocardial perfusion. 2) The observation that
      most ischemic events occur when the levels of sympathetic nerve activity are high
      suggests that the sympathetic nervous system may play a key pathophysiological
      role in this syndrome, as cardiac sympathetic nerve activation can both increase
      metabolic demand and impair myocardial perfusion. 3) beta-Blockers significantly
      reduced episodes of transient myocardial ischemia in these patients, primarily by
      reducing cardiac metabolic requirements. The possibility that sympathetically
      mediated coronary vasoconstriction may also be affected by these drugs needs
      further investigation.

PMID- 1975526
TI  - Medical management of unstable angina. What have we learned from the randomized
      trials?
AB  - Because of the absence of a generally accepted definition of unstable angina, the
      clinical context of drug trials for this condition has varied from trial to
      trial. Early- versus late-entry trials must be distinguished, and the possibility
      of a modification of effect caused by the nature of drug therapy already given
      when the patient became unstable or by concomitant treatment in addition to
      experimental treatment must be taken into account. These factors cannot be
      overlooked when the results from a limited number of reported trials are pooled
      together. The largest early-entry trial with a beta-blocker and a calcium
      antagonist was the Holland Interuniversity Nifedipine/metoprolol Trial (HINT),
      which enrolled patients with suspected unstable angina diagnosed at coronary care
      unit admission. HINT results showed that unstable angina cannot be reliably
      differentiated from evolving myocardial infarction (MI) in this particular
      context and that there are few early MIs that could have been prevented. In
      patients who were not already taking a beta-blocker, metoprolol reduced the
      incidence of acute MI or recurrent ischemia, and there was no benefit of
      nifedipine. On the other hand, the addition of nifedipine was effective in
      patients whose conditions became unstable despite maintenance treatment with a
      beta-blocker. Thus, previous beta-blockade modified the effect of the calcium
      antagonist studied. Based on evidence from HINT and other trials, it is concluded
      that beta-blockers should be used as the first-line treatment in patients with
      unstable angina and that a calcium antagonist should be added when patients
      remain unstable despite beta-blockade.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1975527
TI  - Rabbit leukocyte adhesion molecules CD11/CD18 and their participation in acute
      and delayed inflammatory responses and leukocyte distribution in vivo.
AB  - In humans the glycoprotein complexes CD11/CD18 mediate leukocyte adhesion to
      cells. Mouse monoclonal antibodies (mAb) 60.3, 7E4, and IB4 to human CD18, found
      to cross-react with rabbit white blood cells, were used to identify the antigen
      in rabbit cells and to study adherence of rabbit leukocytes in vitro and in vivo.
      These antibodies labeled almost all unfractionated rabbit blood leukocytes and
      immunoprecipitated surface glycopolypeptides with apparent molecular weights of
      85,000 and 150,000 from these cells. Adhesion of purified rabbit
      polymorphonuclear cells (PMNs) to cultured vascular endothelial cells in the
      presence of phorbol ester was blocked by the antibodies in a dose-dependent
      manner. The acute inflammatory response characterized by local accumulation of
      PMNs and concomitant plasma extravasation following intradermal injections of
      zymosan-activated serum (ZAS) in rabbits was inhibited in animals pretreated
      intravenously with anti-CD18 mAb. Intravital microscopy of the rabbit tenuissimus
      muscle demonstrated that anti-CD18 mAb. Intravital microscopy of the rabbit
      tenuissimus muscle demonstrated that anti-CD18 treatment specifically blocked the
      adhesion of activated leukocytes to the venular endothelium and thereby the
      subsequent diapedesis of these cells into the extravascular space. The lymphocyte
      dependent tissue swelling resulting from a delayed-type hypersensitivity reaction
      in the rabbit ear was partially inhibited by anti-CD18 mAb. Systemic anti-CD18
      treatment induced a pronounced increase in the number of circulating mononuclear
      and polymorphonuclear cells with a maximum at 24 hr after injection of the
      antibody. It is concluded that GP150/GP85 is the rabbit homologue of human
      CD11/CD18, and that leukocyte-cell adhesion mediated by these glycoprotein
      complexes participates in acute and delayed inflammatory responses and leukocyte
      distribution in vivo.

PMID- 1975528
TI  - Ultradian, circahoral and circadian structures in endothermic vertebrates and
      humans.
AB  - 1. For more than 30 years many studies have been carried out concerning rhythms
      with periods approaching 24 hr (circadian rhythms). 2. The latter have been
      demonstrated as resulting from environmental 24 hr synchronizers (zeitgebers),
      but they usually persist in the absence of a 24 hr synchronization, which proves
      their endogenous nature. 3. Biological rhythms with periods less than 20 hr
      (ultradian rhythms) and particularly those approaching 1 hr (circahoral rhythms)
      have been determined: for motility, rest-activity, sleep phases, endocrine
      secretions and other physiological functions. 4. These ultradian and circahoral
      rhythms have been found in rodents, birds, monkeys and humans. 5. Existing at all
      stages of ontogeny, they have been proved to be endogenous and species and strain
      specific. 6. As these ultradian rhythms can be influenced by environmental
      factors and sometimes by circadian rhythms they are not truly periodic, so
      therefore cannot be computed by the usual processes of mathematical time
      analysis.

PMID- 1975529
TI  - Longitudinal study of haematological and biochemical constituents in blood of the
      Asian elephant (Elephas maximus).
AB  - 1. Haematological parameters and biochemical analytes were determined in four
      elephants over a period of one year. 2. The haematological profile remained
      constant over time and was similar between animals. 3. Values for biochemical
      analytes were stable except for alkaline phosphatase, gamma glutamyl transferase
      and creatinine which rose during musth in male elephants. 4. The association of
      elevated enzyme levels with increased testosterone concentrations is discussed.

PMID- 1975530
TI  - CSF ion composition and manipulation during thermoregulation in an avian species,
      Gallus domesticus.
AB  - 1. At thermoneutrality (28 degrees C), CSF Na+:Ca2+ in hens was 61.66; under
      thermal stress (39 degrees C), it changed to 59.38 (30 min), 62.58 (3 hr), and
      52.44 (10 hr); no change in ratio occurred at 15 degrees C. 2. ICV Ouabain and/or
      EGTA increased body temperature (TR) but not respiration rate (RR) at 39 degrees
      C. 3. At 28 degrees C, Ouabain decreased, and EGTA increased, TR and RR. 4. Ca2+
      may be more critical than Na+ in thermoregulation. 5. Heat stress appears to
      stimulate Na+-transport mechanisms other than Na+-ATPase. 6. RR appears to be a
      function of TR, not of ion balance.

PMID- 1975531
TI  - An infrared thermographic study of surface temperature in relation to external
      thermal stress in the Mongolian gerbil, Meriones unguiculatus.
AB  - 1. Temperatures of different body surface regions and deep body temperature (Tb)
      of unrestrained adult Mongolia gerbils exposed to ambient temperatures (Ta) of 
      10-35 degrees C were measured using infrared (i.r.) thermography and a
      thermocouple. 2. A strong positive linear relationship between the surface
      temperature and Ta was found. For Ta range -4-35 degrees C, the slope was lowest
      for the areas around the eyes and dorsal head, and steepest for the body
      extremities. At -10 degrees C, surface temperatures of the areas around the eyes
      and dorsal head were significantly lower then predicted. 3. Tb was lowest at Ta
      of 25 and 30 degrees C, increased at all temperatures above and up to Ta of -4
      degrees C below this range, and began decline at -10 degrees C. 4. The
      thermoneutral zone (TNZ) is probably between 28 and 32 degrees C, and the
      absolute lower critical temperature (Tabsl) is probably -4 degrees C. 5. The
      Mongolian gerbil shows little control of surface temperature and in contrast to
      larger mammals it has not developed any special thermoregulatory surface areas to
      regulate heat exchange with its environment. At temperatures below -4 degrees C,
      this species is unable to maintain the surface temperature of body extremities
      above the freezing point. 6. It is suggested that the Mongolian gerbil uses
      mainly behavioral and ecological adaptive strategies to attenuate the stressful
      effects of its habitat.

PMID- 1975532
TI  - Influence of Ca/Na exchange and diamide on membrane partitioning of
      glyceraldehyde-3-phosphate dehydrogenase in dog red cells.
AB  - 1. Ca/Na exchange in dog red cells is greatly stimulated by pretreatment of the
      cells with diamide, but only if the diamide preincubation is carried out in a Na
      free, Ca-containing medium. 2. Membranes prepared from dog red cells that had
      been pre-exposed to diamide in solutions containing various combinations of Ca
      and Na were subjected to polyacrylamide gel electrophoresis and Western blotting.
      3. The band representing glyceraldehyde-3-phosphate dehydrogenase was selectively
      increased under the very same ionic conditions that result in a diamide-induced
      stimulation of Ca/Na exchange. 4. Glyceraldehyde-3-phosphate dehydrogenase may
      participate in the modulation by diamide of Ca/Na exchange in dog red cells.

PMID- 1975533
TI  - Diurnal changes in the haemoglobin level, red blood cell number and mean
      corpuscular haemoglobin in foals during the first 13 weeks of life and in their
      lactating mothers.
AB  - 1. In six foals and their mothers (of Standard breed) diurnal changes in the
      haemoglobin level, red blood cell number and mean corpuscular haemoglobin during
      the first 13 weeks of foal life were studied. 2. Studies begun when a foal
      reached 7 days of age and were repeated every two weeks till 13 weeks of foal
      life. Blood was taken every 6 hr in foals and every 4 hr in mares. 3. No diurnal
      rhythmicity in parameters studied either in foals or in mares was found. 4.
      Decrease of haemoglobin level in lactating mares (14.0-12.5 g/100 ml) without
      changes in red blood cell number were observed. Mean corpuscular haemoglobin
      changed distinctly from one study day to another. 5. In foals were stated:
      significantly higher haemoglobin level and erythrocyte number and lower mean
      corpuscular haemoglobin than in mares.

PMID- 1975534
TI  - Intestinal transport of potassium. Effects of changing apical and basolateral
      influx of sodium in the isolated mucosa of the hen (Gallus domesticus) colon.
AB  - 1. Net potassium secretion (JKnet) by the sodium-depleted hen's colon (low sodium
      colon) is 0.17 +/- 0.07 mumol/cm2.hr. Amiloride or ouabain eliminates short
      circuit currents (Isc) of 16-20 mumol/cm2.hr without affecting JKsm. 2. In the
      NaCl-loaded hen's colon (high sodium colon) stimulating Isc by (a) glucose, (b)
      amino acids, and inhibiting with (c) ouabain changes JKnet from 0.08 +/- 0.04 to
      (a) 0.42 +/- 0.07, to (b) 0.60 +/- 0.07 to (c) 0.13 +/- 0.13 mumol/cm2.hr. 3. In
      both colonic types theophylline increases and bumetanide decreases JKnet by 1
      mumol/cm2.hr. 4. CONCLUSION: Apical membranes of sodium-absorbing and chloride
      secreting cells of the high sodium colon are potassium permeable. In the low
      sodium colon sodium-absorbing cells have potassium-impermeable apical membranes.

PMID- 1975535
TI  - In vitro studies of theophylline-induced changes in Na, K and Cl transport in hen
      (Gallus domesticus) colon suggesting bidirectional, basolateral NaK2Cl
      cotransport.
AB  - 1. In isolated mucosa from a NaCl-loaded hen theophylline stimulates both
      unidirectional chloride fluxes (JmsCl and JsmCl). Conductive and electroneutral
      exchange processes, besides a bumetanide-sensitive, rheogenic process contribute.
      2. The bumetanide-sensitive fraction of the theophylline-induced delta JcmCl is
      sodium-dependent. 3. Incubation in nominally K(+)-free solutions reduces the
      bumetanide-sensitive fraction delta JsmCl more than treatment with ouabain. 4.
      With respect to chloride the bumetanide-sensitive fraction of delta JsmCl has a
      Hill coefficient of 1.93 +/- 0.03, a Jmax of 12.9 +/- 0.2 mumol/cm2.hr and a K
      1/2 of 73 +/- 1 mmol/l. 5. After ouabain treatment delta JmsCl and delta JsmCl
      are equally sensitive to bumetanide, while delta JmsCl is bumetanide insensitive
      without ouabain treatment.

PMID- 1975536
TI  - Absence of transovarial transmission of bluetongue virus in Culicoides
      variipennis: immunogold labelling of bluetongue virus antigen in developing
      oocytes from Culicoides variipennis (Coquillett).
AB  - 1. Culicoides variipennis midges were fed on a blood meal containing bluetongue
      virus (BTV) serotype 11 (BTV-11) and on four subsequent non-infective blood meals
      at 4-day intervals. 2. Eggs were collected before each blood-feeding and reared
      to adults. 3. Progeny from each egg batch were incubated for 14 days (20 degrees
      C, 40-60% RH) before plaque assay. 4. Oocytes from several parent flies were
      sectioned for immunoelectron microscopy. 5. Thirty-two percent of the parent
      females tested by plaque assay were positive for BTV. 6. All 993 progeny flies
      were negative for BTV. 7. BTV antigen was dense in proteid yolk bodies and in the
      vitelline membrane of the developing oocytes.

PMID- 1975537
TI  - Effect of breed of horse on muscle carnosine concentration.
AB  - 1. Muscle samples from the M. gluteus medius were obtained from six Quarter
      Horses (QH), six Thoroughbreds (TB), and five Standardbreds (SB) to determine
      carnosine values and fiber type percentages. 2. Muscle biopsies were for fiber
      type percentages and carnosine concentration. 3. QH had a lower percentage of
      slow twitch oxidative fibers and a higher percentage of past twitch glycolytic
      fibers than SB or TB. 4. Fast twitch oxidative-glycolytic fibers were lowest in
      the QH. 5. The QH had mean carnosine values significantly greater (P less than
      0.01) than the mean values for SB and TB. 6. Across breeds muscle carnosine
      concentration was positively correlated (P less than 0.05; r = 0.53) with fast
      twitch glycolytic fiber percentage and negatively correlated (P less than 0.05, r
      = -0.51) with fast twitch oxidative fiber percentage. 7. Free intramuscular
      carnosine is believed to function as an intracellular buffer. Since carnosine was
      highest in the muscle of horses with the greatest percentage of fast twitch
      glycolytic fibers, these data are consistent with the proposed function of this
      dipeptide.

PMID- 1975538
TI  - Milk yield and composition in the punare Thrichomys apereoides.
AB  - 1. Per cent fat composition of the milk was unusually high, ranging from 30.2 +/-
      0.8% on day 2, to 21.0 +/- 1.0% on day 21. 2. Per cent protein changed
      significantly over time, ranging from 11.9 +/- 0.6% to 17.4 +/- 0.9%. 3. Lactose
      content was low, and decreased significantly over time, from 4.62 +/- 0.1% to
      2.65 +/- 0.1%. 4. Milk production peaked at day 14 and ceased by day 35. 5. The
      unusual milk composition of this tropical rodent, is one of several adaptations
      correlated with reproduction in a xeric environment.

PMID- 1975539
TI  - Metamorphic rate as a function of the light/dark cycle in Rana pipiens larvae.
AB  - 1. The rate of development of Rana pipiens tadpoles in spontaneous and thyroxine
      (T4)-induced metamorphosis was studied on light/dark (LD) cycles in which the
      photophase was held constant while the scotophase was progressively extended or
      vice versa. 2. Metamorphic rate fluctuated in both types of experiments as the LD
      cycle lengthened. However, the pattern of resonance differed with the length of
      the photophase. For example, with an 8 hr light phase, development rate slowed
      and then increased as the cycle was extended from 24 to to 36 hr, whereas with a
      12 hr photophase the reverse took place. 3. The findings are compatible with the
      occurrence of a rhythm of light sensitivity in photoperiodic time measurement in
      this amphibian. 4. From the viewpoint of hormonal mechanisms, it is suggested
      that photoperiodic effects on metamorphic rate result from different patterns of
      melatonin secretion under the various LD cycles, since melatonin can modify the
      action of T4 in metamorphosis.

PMID- 1975540
TI  - Comparative length-tension relationship of urinary bladder strips from hamsters,
      rats, guinea-pigs, rabbits and cats.
AB  - 1. Comparative passive tension-active tension curves were constructed for urinary
      bladder body strips from hamster, rat, guinea-pig, rabbit and cat. 2. Equally
      sized strips from rabbit and cat bladders had a significantly greater mass and
      cross-sectional area than strips from other species. 3. There was a greater
      change in cross-sectional area of strips from rabbit and cat bladders with
      increasing length than in strips from other species. 4. Cat bladder strips
      developed a significantly greater absolute active tension than did strips from
      all other species at passive tensions greater than 5 g. 5. The length-tension
      relationships of the urinary bladder differs from skeletal or vascular smooth
      muscle in that there is no significant decrease in active tension at strip
      lengths greater than L0. 6. The ability of the urinary bladder to generate active
      tension at tissue lengths considerably greater than L0 is a prime importance in
      the physiological role of the urinary bladder to accommodate and store urine.

PMID- 1975541
TI  - Water metabolism in the Namib Desert golden mole, Eremitalpa granti namibensis
      (Chrysochloridae).
AB  - 1. Laboratory and field studies of energy and water metabolism employing isotopic
      dilution methods examined the ability of Namib Desert moles to survive on an
      insect diet without drinking water. 2. Water independence is achieved through
      efficient renal function while low rates of energy usage and torpor are further
      effective in reducing overall water requirements.

PMID- 1975542
TI  - Renal physiology of the pig: application of stop-flow.
AB  - 1. The stop-flow method in the pig, with modified kidneys, produced patterns for
      sodium, chloride, glucose and PAH that were similar to those obtained previously
      in other animals with simple kidneys. 2. Ethacrynic acid, under the conditions of
      the experiment, abolished distal sodium and chloride reabsorption in the pig. 3.
      We conclude that this method, viewed in perspective, could provide useful in situ
      information about the physiology of modified kidneys where the more difficult
      micropuncture and in vitro perfusion techniques are impractical.

PMID- 1975543
TI  - Relationship of hypokalemia to metabolic alkalosis in the intact Yucatan
      miniature boar following implantation of deoxycorticosterone-acetate (DOCA) or d
      aldosterone.
AB  - 1. Normo-kalemic Yucatan miniature boars were implanted with deoxycorticosterone
      acetate (DOCA) or d-aldosterone (Aldo) to evaluate the relationship of
      hypokalemia to the pathogenesis of metabolic alkalosis following
      mineralocorticoid administration. 2. Serum potassium was significantly less than
      control within 24 hr, serum bicarbonate significantly elevated within 4 days and
      pH 1-2 days later with no significant differences between DOCA and Aldo. 3. These
      data demonstrate that pre-existing potassium deficits are not required for the
      development of alkalosis with mineralocorticoid administration, DOCA and Aldo are
      equally effective, co-existing hypokalemia is necessary in the genesis, and
      perhaps maintenance, of metabolic alkalosis with excess mineralocorticoids, and
      hypokalemia is not a consequence of the alkalosis.

PMID- 1975544
TI  - Membrane transport of sodium ions in erythrocytes of the American black bear,
      Ursus americanus.
AB  - 1. Membrane transport of Na ions was investigated in red blood cells of bears by
      methods of measurement of unidirectional isotopic fluxes. 2. Like red blood cells
      of dogs, bear red cells contain a high Na concentration and low concentrations of
      K and ATP. 3. As in dog red cells, Na efflux from bear cells was not inhibited by
      ouabain but was activated by the presence of Ca in the medium, possibly
      indicating the presence of a Na-Ca exchange mechanism. 4. ATP depletion of cells
      was accelerated by Ca in the medium, consistent with the presence of a strong ATP
      dependent Ca pump. 5. As in other carnivore red cells, Na influx into bear cells
      was strongly activated by shrinkage and inhibited by swelling. Shrinkage
      activated influx was blocked by amiloride. 6. Amiloride-sensitive influx was
      activated by cytoplasmic Ca and also correlated with the presence of a Na
      dependent, amiloride-sensitive H loss. 7. Amiloride-sensitive Na influx exhibited
      a strong seasonal cycle with a minimum in the middle of the hibernation period,
      suggesting a possible avenue of cellular energy conservation.

PMID- 1975545
TI  - Membrane transport of potassium ions in erythrocytes of the American black bear,
      Ursus americanus.
AB  - 1. Membrane transport of K ions was investigated in red blood cells of bears by
      methods of measurement of unidirectional isotopic fluxes. 2. Unlike red cells of
      dogs, red cells of bears exhibited a significant, though small, component of
      ouabain-sensitive K influx. 3. Ouabain-insensitive K influx, as in other
      carnivore cells, was activated by swelling and inhibited by shrinkage. Swelling
      induced K influx was dependent upon presence of chloride ions but was not
      inhibited by furosemide or bumetanide. 4. Ouabain-sensitive K influx was largest
      with ATP and with high concentration of Na in the cell, but it persisted in the
      absence of cytoplasmic Na or ATP. It was also resistant to the drug, harmaline,
      at a concentration that in other cells fully inhibits ouabain-sensitive K influx.
      5. It was concluded that under such adverse conditions ouabain-sensitive K influx
      represents another mode of the Na/K pump not fully described elsewhere. 6. Also,
      as in low K red cells of sheep and goat, apparent absence of Na/K pump activity
      in carnivore red cells may represent suppression rather than elimination of
      activity. 7. Ouabain-insensitive K influx showed a seasonal pattern with minima
      occurring in early winter, earlier than for the minimum observed in Na influx. 8.
      Ouabain-sensitive K influx tended to be lower in the hibernation season of the
      bear, but the seasonal pattern was not consistent.

PMID- 1975546
TI  - NMDA receptors contribute to the resting discharge of vestibular neurons in the
      normal and hemilabyrinthectomized guinea pig.
AB  - Excitatory amino acids (EAA) like L-Glutamate or L-Aspartate have been suggested
      to be the neurotransmitters at the synapses between primary vestibular afferents
      and second-order vestibular neurons. In the first part of our work, we have
      tested the possibility that EAA receptors are implicated in the control of
      posture by vestibular nuclei. Normal guinea pigs were implanted with minipumps
      delivering EAA antagonists in the vestibular nuclei. Their resting posture was
      monitored during the perfusion by using an X-ray photographic method. Chronic
      infusion of D-L-2-amino-5-phosphonovaleric acid (APV), a specific antagonist of
      NMDA receptors, in the vestibular nuclei induced a postural and oculomotor
      syndrome similar to the one observed following acute vestibular deafferentation.
      Administration of 6-cyano-7-nitro-quinoxaline-2-3-dione (CNQX), a specific
      antagonist of kainate and quisqualate receptors, failed to induce any postural
      syndrome or eye deviation. These results suggest that, under physiological
      conditions, N-methyl-D-aspartate (NMDA) receptors, contrary to kainate and
      quisqualate receptors, are essential for the maintenance of a symmetric posture
      and of a normal eye position at rest. Previous electrophysiological studies have
      demonstrated that following unilateral labyrinthectomy the recovery of a resting
      discharge in the deafferented vestibular nuclei plays a key role in the
      compensation of postural disorders. In the second part of this study, we have
      tested whether NMDA receptors could be implicated in this postural recovery. APV
      mini-pumps were implanted in hemilabyrinthectomized guinea pigs after complete
      compensation. A postural decompensation was induced, which occurred after
      delivery of the same amount of APV which provoked a vestibular syndrome in intact
      guinea pigs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1975547
TI  - Catecholamine-containing axon terminals in the hypoglossal nucleus of the rat: an
      immuno-electronmicroscopic study.
AB  - A correlative light and electron microscopic investigation was undertaken to
      determine the morphology and distribution of catecholamine (CA)-containing axon
      terminals in the hypoglossal nucleus (XII) of the rat. This was accomplished
      immunocytochemically with antibody to tyrosine hydroxylase (TH). The major
      findings in this study were the following: 1) Immunoreactive profiles were found
      throughout XII and included unmyelinated axons, varicosities, axon terminals and
      dendrites; 2) Nonsynaptic immunoreactive profiles (preterminal axons,
      varicosities) were more frequently observed (55.2%) than synaptic profiles
      (43.5%); 3) CA-containing axon terminals ending on dendrites were more numerous
      (71.8%) than those synapsing on somata (25.4%) or non-labeled axon terminals
      (2.7%); 4) The morphology of labeled axon terminals was variable. Axodendritic
      terminals typically contained numerous small, round agranular vesicles, a few
      large dense-core vesicles and were associated with either a symmetric or no
      synaptic specialization, axosomatic terminals were often associated with a
      presynaptic membrane thickening or a symmetric synaptic specialization and
      contained small, round and a few elliptical-shaped vesicles, while axoaxonic
      synapses formed asymmetric postsynaptic specializations; and 5) CA-positive
      dendritic processes were identified in XII. These findings confirm the CA
      innervation of XII, and suggest a complex, multifunctional role for CA in
      controlling oro-lingual motor behavior.

PMID- 1975548
TI  - [The role of the dopaminergic system and GABA-benzodiazepine- ionophore complex
      in the regulation of memory retrieval].
AB  - The spontaneous forgetting model has been used to demonstrate the possibility of
      the memory forgetten trace extraction under the dopamine reuptake blockade by
      nomifensine and bupropion, increase of its quantity by amfonelic acid, activation
      of the postsynaptic dopaminergic receptors by (+)3-PPP, blockade of the latter by
      (-)3-PPP, and under the blockade of separate links of the GABA-benzodiazepine
      ionophore complex by bicuculline, picrotoxin, flumazepil and R015-3505.
      Effectiveness of the neuropharmacological actions improving the memory forgotten
      trace retrieval is shown to depend upon the duration of the spontaneous
      forgetting process. The presynaptic receptors are involved in the retrieval
      process control--improvement of the conditioned habit performance after
      forgetting due to the activation of presynaptic dopaminergic receptors by
      specific agonist (-)3-PPP is clearly correlated with the initial retrieval level.
      The above facts underlie a hypothesis about the neurochemical forgetting
      mechanisms.

PMID- 1975549
TI  - Endoscopic laser lithotripsy of large bile duct stones.
AB  - Experimental work has established that the Candela (Candela Laser Corporation,
      Wayland, MA) flashlamp excited dye laser (wavelength, 504 nm) is a highly
      effective method for fragmenting biliary stones and has minimal potential for
      injuring the bile duct wall. This technique was evaluated in 25 complex patients
      whose stones, usually because of large size, did not respond to standard
      nonoperative treatment. The laser imaging was applied through a quartz fiber and
      aimed either under direct vision with choledochoscopes passed percutaneously or
      through a special "mother" duodenoscope or under fluoroscopic guidance at
      standard duodenoscopy. Laser treatment resulted in some fragmentation of stones
      in 23 cases. Subsequently, it proved that it was possible to clear the bile duct
      of stones in 20 patients, 12 of them receiving successful treatment during the
      same endoscopic procedure. There were no significant complications. This
      endoscopic technique seems to be a useful new alternative to surgery in patients
      with large and difficult bile duct stones.

PMID- 1975550
TI  - Gastrin stimulates the self-replication rate of enterochromaffinlike cells in the
      rat stomach. Effects of omeprazole, ranitidine, and gastrin-17 in intact and
      antrectomized rats.
AB  - The enterochromaffinlike cells in the rat stomach are rich in histamine and are
      thought to be under the influence of gastrin. The effect of sustained endogenous
      and exogenous hypergastrinemia on the activity and proliferation rate of the
      enterochromaffinlike cells was studied by determining the histidine decarboxylase
      activity and histamine concentration and by combining histamine
      immunocytochemistry and autoradiography after in vivo labeling with
      [3H]thymidine. The proliferation rate of the stem cells in the oxyntic mucosal
      progenitor zone was also studied. Exogenous hypergastrinemia was induced by
      infusion of rat gastrin-17 (60 nmol.kg-1.day-1). Endogenous hypergastrinemia was
      induced by inhibition of gastric acid secretion with omeprazole (80 mumol.kg
      1.day-1) or ranitidine (1200 mumol.kg-1.day-1). The effect of omeprazole was also
      studied in antrectomized rats. In intact rats, all treatments resulted in
      elevated plasma gastrin levels and were accompanied by an increase in the
      histidine decarboxylase activity and the histamine content of the oxyntic mucosa.
      This resulted in an increase in the enterochromaffinlike cell proliferation rate,
      leading to enterochromaffinlike cell hyperplasia. The number of labeled stem
      cells was increased, but this effect was not as pronounced as in the
      enterochromaffinlike cells. In antrectomized rats, the inhibition of acid
      secretion by omeprazole did not result in elevated plasma gastrin or in an
      increase in the activity or number of enterochromaffinlike cells, indicating that
      omeprazole per se had no effect on these cells. These data support the view that
      gastrin stimulates the proliferation rate of both enterochromaffinlike cells and
      stem cells. Gastrin also stimulates the activity of the enterochromaffinlike
      cells.

PMID- 1975551
TI  - [Principles of treatment of occupational diseases caused by antibiotics].
AB  - The contributors expound the major principles of occupational diseases treatment
      from antibiotics and propose to cope with the allergic reactions and
      dysbacteriosis with due account of the underlying pathogenic mechanisms.
      Microcirculation influencing drugs and corticosteroid therapies were proposed to
      deal with more severe cases, particularly with secondary allergic NS vasculites.
      Abstention from antibiotics and a long-term complex treatment resulted in health
      improvement and working capacity rehabilitation.

PMID- 1975552
TI  - ABO blood type predicts the cytolocalization of anti-P-glycoprotein monoclonal
      antibody reactivity in human colon and ureter.
AB  - Classic multidrug resistance is mediated by a P-glycoprotein. Using monoclonal
      antibody C219 (MAb C219) in an immunohistochemical study, we found high levels of
      putative Golgi P-glycoprotein in normal columnar and transitional epithelium in
      subpopulations of patients with specific blood types. For example, Golgi staining
      was present in blood type A patients in 46% of normal colon samples (N = 21) and
      88% of normal ureter samples (N = 17). In comparison, Golgi staining was present
      in blood group O patients in only 6% of normal colon samples (N = 34) and in 0%
      of normal ureter samples (N = 19). The association of MAb C219 Golgi staining
      with blood type A and lack of Golgi staining with blood type O was statistically
      significant in normal colon (P = .001) and normal ureter (P less than .0001).
      Inappropriate hyperexpression of P-glycoprotein was frequently found in colon
      carcinomas. Additional evidence that Golgi MAb C219 reactivity represents P
      glycoprotein is presented. This includes (1) immunostaining of Golgi with two
      anti-P-glycoprotein MAbs, C219 and JSB-1, and (2) experiments in which Mab C219
      Golgi reactivity was blocked by preincubation of MAb C219 with a specific P
      glycoprotein epitope-containing peptide. The high degree of association of Golgi
      P-glycoprotein with blood type A may suggest a role for P-glycoprotein in
      processing or trafficking of specific blood group antigens.

PMID- 1975553
TI  - Studies on DNA markers (D4S10 and D4S43/S127) genetically linked to Huntington's
      disease in Japanese families.
AB  - This is the first full report on the genetic linkage between Japanese
      Huntington's disease and the DNA markers D4S10 and D4S43/S127. With use of the
      HindIII, BglI, and EcoRI polymorphisms detected at D4S10, and the combination of
      all these polymorphisms to give composite haplotypes, nine Japanese Huntington's
      disease families were found to be informative. Three recombinants for D4S10 were
      detected in these families, giving a maximum lod score of 1.662 at a theta of
      0.10. Similarly, when we used the MspI and PvuII polymorphisms detected by
      D4S43/S127, five families gave informative results. No recombinant was detected
      in these families, giving a maximum lod score of 3.348 at a theta of 0.00. These
      results clearly support the view that the Japanese Huntington's disease gene may
      be identical with the Western gene, in spite of the lower prevalence rate in
      Japan.

PMID- 1975554
TI  - Molecular characterization of beta-thalassemia mutations in Egypt.
AB  - The relative frequency of different beta-thalassemia mutations and their
      association with beta-globin haplotypes were studied in patients from the Nile
      delta region, Egypt, by means of the polymerase chain reaction, oligonucleotide
      hybridization and restriction analysis. We found that 8 mutations account for 77%
      of beta-thalassemia chromosomes in this population, the commonest being IVS-1 nt
      110, IVS-1 nt 6 and IVS-1 nt 1. Each mutation was associated with a specific
      haplotype, with the exception of IVS-1 nt 110, found on 3 different chromosomal
      backgrounds. Our data show that testing for the 8 detectable mutations makes
      feasible prenatal diagnosis in 65% of at risk couples and exclusion testing in an
      additional 25% of cases.

PMID- 1975555
TI  - Prenatal diagnosis and linkage disequilibrium with cystic fibrosis for markers
      surrounding D7S8.
AB  - Three polymorphic DNA markers surrounding the D7S8 locus were tested for their
      usefulness in the diagnosis of cystic fibrosis (CF) by linkage analysis. The
      markers correspond to the loci D7S424 and D7S426. These polymorphisms were
      studied by centers in the U.S., the United Kingdom, the Netherlands, and Italy,
      using samples from populations throughout Europe and North America. The
      additional information provided by these probes increased the heterogeneity of
      the region from 50% to 58% and was essential for a completely informative
      diagnosis in one family. A very high degree of linkage disequilibrium was found
      between these markers, which span a distance of approximately 250 kb. In
      addition, linkage disequilibrium with CF was noted. Significant heterogeneity of
      linkage disequilibrium was found among the populations, both for the marker
      marker pairs and between the markers and CF.

PMID- 1975556
TI  - HLA class I gene polymorphism in genetic hemochromatosis.
AB  - The authors have studied HLA class I polymorphism in an attempt to identify a
      genomic marker of the hemochromatosis gene. Five enzymes were used (HindIII,
      EcoRI, EcoRV, PvuII, and HincII) in 47-106 unrelated patients and 71-91 controls.
      Both populations were HLA-typed. The relationship between the restriction
      fragments and HLA-A antigens was considered. Comparison of the two groups
      revealed a significantly high frequency of one 14 kb EcoRI fragment among the HLA
      A3 hemochromatosis patients. The fragment hybridizes to an HLA-A specific probe
      but not to an HLA-B specific probe, and is associated with the hemochromatosis
      gene, which is itself associated with HLA-A3.

PMID- 1975557
TI  - Somatic origin of inherited haemophilia A.
AB  - We found a partial deletion of the clotting factor VIII gene of about 2000 bp,
      spanning exon 5 and part of intervening sequence 4 and 5 in an isolated patient
      with severe haemophilia A. The mother of the patient, who appeared to be a non
      carrier on the basis of coagulation assays and restriction fragment length
      polymorphism analysis in the family, turned out to be a mosaic for the deletion,
      not only in her germ cells, but also in various somatic cells. These findings
      suggest that the mutation is the result of an event in early embryogenesis. If
      mosaicism for a mutation, either gonadal or somatic, proves to be a common
      phenomenon in human genetics, it is imperative to reconsider genetic risks for
      (future) sibs of any apparently new mutant of a hereditary disease.

PMID- 1975558
TI  - Prenatal diagnosis of alpha-thalassemia by polymerase chain reaction and dual
      restriction enzyme analysis.
AB  - Asian couples at risk for a fetus with homozygous alpha-thalassemia (hydrops
      fetalis) are often identified by their low erythrocyte mean corpuscular volume
      (MCV) and normal hemoglobin electrophoresis when little time remains to test
      their genotypes by restriction enzyme analysis. DNA analysis is performed
      directly on chorionic villi or amniocytes remaining after an aliquot is used to
      establish a backup cell culture. The polymerase chain reaction (PCR) protocol
      quickly determines whether the fetus has hydrops fetalis without waiting for
      cultured cells to grow. Previously, growing cultured fetal cells to obtain more
      fetal material to establish unambiguously the fetal genotype with two independent
      restriction enzyme digests absorbed a significant portion of the time remaining
      to complete prenatal diagnosis. A dual restriction enzyme digestion protocol was
      development using a 3' zeta-globin probe to clearly distinguish the most common
      alpha-thalassemia deletions that represent nearly all the alpha-thalassemia
      haplotypes in Southeast Asia.

PMID- 1975559
TI  - Two mutations within the coding sequence of the phenylalanine hydroxylase gene.
AB  - Two previously unidentified mutations at the phenylalanine hydroxylase locus were
      found during a study of the relationship between genotype and phenotype in
      phenylketonuria and hyperphenylalaninemia. One mutation eliminates the BamHI site
      in exon 7 and the other eliminates the HindIII site in exon 11 of the
      phenylalanine hydroxylase gene. They were suspected because of deviating
      restriction fragment patterns and confirmed by amplification, via the polymerase
      chain reaction, of exon 7 and exon 11, respectively, followed by digestion with
      the appropriate restriction enzyme. Direct sequencing of amplified mutant exon 7
      revealed a G/C to T/A transversion at the first base of codon 272, substituting a
      GGA glycine codon for a UGA stop codon. Direct sequencing of amplified mutant
      exon 11 revealed a deletion of codon 364, a CTT leucine codon. The exon 7
      mutation can be expected to result in a truncated protein and the exon 11
      mutation in the elimination of an amino acid in the catalytic region of the
      enzyme. A patient who is a compound heterozygote for these two mutations has
      classical phenylketonuria. It is concluded that each of the two mutations leads
      to a profound loss of enzymatic activity. The segregation of these mutations with
      disease alleles in 4 and 2 families, respectively, supports the hypothesis that
      multiple mutations at the phenylalanine hydroxylase locus explain the variable
      phenylalanine tolerance in patients with phenylalanine hydroxylase deficiency.

PMID- 1975561
TI  - Distribution and characterization of a Sandhoff disease-associated 50-kb deletion
      in the gene encoding the human beta-hexosaminidase beta-chain.
AB  - A 50-kb deletion was demonstrated in the gene encoding for the beta-subunit of
      human hexosaminidase (HEXB), using field inversion gel electrophoresis (FIGE) of
      SfiI-digested chromosomal DNA from patients with Sandhoff disease. We
      investigated 14 patients from different parts of Europe and found no deletion in
      5 patients, 2 patients homozygous for the deletion, and 7 patients with the
      deletion in one allele. The distribution of the 50-kb deletion was approximately
      in agreement with the Hardy-Weinberg equilibrium. The deletion was characterized
      using chromosomal DNA from one of the two homozygous patients. Restriction
      fragments were hybridized with a 1.6-kb (almost complete) and a 0.4-kb (5') HEXB
      cDNA clone. It appeared that the deletion started in intron 5, extending in the
      5' direction and causing the loss of exon 1-5 and the promoter area of the HEXB
      gene.

PMID- 1975560
TI  - Linkage relationships of the apolipoprotein C1 gene and a cytochrome P450 gene
      (CYP2A) to myotonic dystrophy.
AB  - We have studied the genetic linkage of two markers, the apolipoprotein C1 (APOC1)
      gene and a cytochrome P450 (CYP2A) gene, in relation to the gene for myotonic
      dystrophy (DM). A peak lod score of 9.29 at 2 cM was observed for APOC1-DM, with
      a lod score of 8.55 at 4 cM for CYP2A-DM. These two markers also show close
      linkage to each other (theta max = 0.05, Zmax = 9.09). From examination of the
      genotypes of the recombinant individuals, CYP2A appears to map proximal to DM
      because in one recombinant individual CYP2A, APOC2 and CKMM had all recombined
      with DM. Evidence from another CYP2A-DM recombinant individual places CYP2A
      proximal to APOC2 and CKMM. Localisation of CYP2A on a panel of somatic cell
      hybrids also suggests that it is proximal to DM and APOC2/C1/E gene cluster.

PMID- 1975562
TI  - IgG antibody and delayed-type hypersensitivity responses in nude mice grafted
      with thymic epithelium.
AB  - This study compared the ability of foetal thymic epithelium depleted of
      lymphocytes and dendritic cells, by low temperature or deoxyguanosine (dGuo)
      treatment in organ culture, to reconstitute T-cell function in nude mice. It is
      shown that renal capsule grafts of either type could promote the development of
      functional T lymphocytes in the periphery, as judged by in vivo assays. Both
      syngeneic and allogeneic thymic epithelium endowed nude mice with the capacity to
      mount IgG antibody and delayed-type hypersensitivity (DTH) responses to the T
      dependent antigen ovalbumin (OVA). Functional reconstitution was accompanied by
      the appearance of Thy-1-bearing cells in the spleens of thymic grafted nude mice.
      The results from allogeneically grafted recipients show that a substantial
      population of peripheral T cells was present that collaborated with B cells and
      other antigen-presenting cells (APC) which do not express major
      histocompatibility complex (MHC) molecules of the thymus donor haplotype.

PMID- 1975563
TI  - A computer program to assist in the choice of restriction endonucleases for use
      in DNA analyses.
AB  - Type II restriction endonucleases cleave double stranded DNA molecules at sites
      characterized by one or more sets of nucleotide pairs sequences. These digestions
      are essential in such procedures as DNA cloning, DNA sequencing and restriction
      fragment length polymorphism (RFLP) analyses. A large number of enzymes with
      different sequence specificities are available. To date, most choices of
      restriction endonucleases have been made by trial and error. A computer program,
      REDI, has been developed that predicts the ability of a particular restriction
      enzyme to detect mutations. Characteristics of both the restriction endonuclease
      used and the DNA being cut are incorporated as variables in the program. The
      program was tested using mouse mitochondrial DNA (mtDNA) and bacteriophage lambda
      DNA because these have been sequenced and are well characterized. REDI was
      strongly correlated (rs = +0.862, n = 11, P less than 0.001) with mouse mtDNA
      RFLP detected by Ferris et al. [1] (Genetics, 105 (1983) 681-721). Even though
      predictions may be altered by a non-random association of nucleotides, which
      varies among DNA molecules, the predictions increase the probability of selecting
      the most efficient enzymes for use in the analysis of a particular DNA molecule.

PMID- 1975564
TI  - Abnormal expression and structural modification of the insulin-like growth-factor
      II gene in human colorectal tumors.
AB  - The insulin-like growth factor II (IGF-II) is a small protein implicated in fetal
      growth and development. It may play a role in the neoplastic process. The IGF-II
      gene is located on the short arm of chromosome II near insulin and c-Ha-ras I
      genes. Three distinct promoters control the transcription of this gene, leading
      to different IGF-II mRNA species. We have analyzed 21 human colorectal tumors and
      found overexpression of IGF-II in 6 of them (30%). When compared with expression
      in normal adjacent tissues, IGF-II mRNA increase in these tumors was either
      moderate (2- to 15-fold) or very marked (200- to 800-fold). In situ hybridization
      experiments confirmed that high IGF-II mRNA amounts were localized in cancer
      cells of the tumors overexpressing the IGF-II gene. In addition, DNA analysis
      revealed a structural modification of one IGF-II locus in one tumor characterized
      by very high IGF-II mRNA.

PMID- 1975565
TI  - Restriction fragment length polymorphism analysis of the L-myc gene locus in a
      case-control study of lung cancer.
AB  - The L-myc DNA-restriction fragment length polymorphism, revealed by EcoRI, has
      been studied in both a lung cancer case-control framework and a cohort of 40 non
      diseased unrelated individuals. No association was found between the L-myc
      allelic frequencies and disease status, tumor stage or lung cancer histology. A
      strong association was, however, observed between the L-myc allelic frequencies
      and ethnic origin (black or white) of the subjects. Among American whites the
      allelic distribution at the L-myc proto-oncogene locus was almost identical to
      that previously reported for Japanese subjects. Among the American black
      population there was a significantly higher frequency of the presence of the
      polymorphic EcoRI restriction site in the second intron of the L-myc proto
      oncogene. These data emphasize the importance of conducting epidemiologic studies
      that control for ethnic factors and indicate that L-myc EcoRI allelotypes do not
      appear to be predictive of lung cancer risk or disease status in American blacks
      and whites.

PMID- 1975566
TI  - ICAM- melanoma cells are relatively resistant to CD3-mediated T-cell lysis.
AB  - The primary activation pathway of T cells is via the T-cell receptor (TCR)/CD3
      complex, which is functionally interrelated with various accessory molecules. We
      examined the contribution of the lymphocyte-function-associated antigen
      I/intercellular adhesion molecule 1 (LFA-1/ICAM-1) interaction to CD3/TCR
      mediated lysis by cytotoxic T lymphocytes (CTL). We used ICAM-I-or+ tumor cell
      lines as target cells and anti-CD3- or anti-LFA-1 containing hetero-cross-linked
      monoclonal antibody (MAb) to bridge CTL and target cells and simultaneously to
      activate CTL. The ICAM-1- melanoma-derived cell line IgR39 was relatively
      resistant to CD3-mediated lysis by both TCR alpha beta + and TCR gamma delta +
      CTL, when compared with ICAM-1+ cell lines. Induction of ICAM-1 on the membrane
      of IgR39 cells by tumor necrosis factor (TNF) rendered these cells more
      susceptible to CD3-mediated lysis. Anti-ICAM-1 MAb inhibited this TNF-enhanced
      susceptibility to lysis, directly demonstrating that the induction of ICAM-1 was
      critical in the TNF-induced increase in susceptibility to lysis of IgR39 cells.
      CTL formed less efficient conjugates with the ICAM-1- cells as compared to ICAM
      1+ cells. Both spontaneous and CD3-induced conjugate formation as well as CD3
      mediated lysis of ICAM-1- tumor cells by CTL were enhanced by the addition of
      anti-LFA-1 containing hetero-cross-linked MAb, thereby mimicking the LFA-1/ICAM-1
      interaction between CTL and target cells. Soluble anti-CD18 MAb inhibited CD3
      mediated lysis of ICAM-1- target cells by CTL without affecting their conjugate
      formation. Anti-LFA-1 MAb added after conjugate formation still inhibited lysis
      of both ICAM-1+or- tumor cells. Taken together, these findings suggest that the
      LFA-1/ICAM-1 interaction co-activates CD3/TCR-mediated lysis by CTL through both
      an enhanced CTL-target cell binding and the delivery of post-conjugate
      costimulatory signals.

PMID- 1975567
TI  - Human melanoma cells with high susceptibility to cell-mediated lysis can be
      identified on the basis of ICAM-1 phenotype, VLA profile and invasive ability.
AB  - Marked heterogeneity for susceptibility to lysis by autologous CTL clones and
      allogeneic IL-2-activated CD3- and CD3+ lymphocytes was found among 19 clones
      isolated from a human metastatic melanoma (Me665/2). A subset of 5 clones with
      the highest susceptibility to lysis had increased ICAM-1 antigen expression.
      Phenotype analysis for the presence of extracellular matrix receptors in the beta
      1- and beta 3-integrin families revealed that the tumor clones with the highest
      susceptibility to lysis were also characterized by frequent expression or
      increased expression of multiple receptors in the beta 1 family including VLA-1, 
      2, -3, -4 and -6. The correlation between phenotypic markers and susceptibility
      to lysis, seen at the clonal level, was confirmed by selection experiments on the
      uncloned metastasis Me665/2. In fact, the neoplastic population surviving 3
      cycles of immunoselection with IL-2-activated lymphocytes exhibited, in
      comparison to the unselected metastasis: (1) reduced susceptibility to lysis and
      (2) reduced expression of ICAM-1 and of VLA antigens. In contrast, enhanced
      susceptibility to lysis and up-regulation of ICAM-1, VLA-1 and VLA-3 antigens
      were observed on melanoma cells recovered after invading a reconstituted basement
      membrane. These data indicate that melanoma cells with enhanced susceptibility to
      cell-mediated lysis can be identified on the basis of phenotypic characteristics
      (ICAM-1 and VLA antigen profile) and functional features (invasive ability on
      reconstituted basement membranes).

PMID- 1975568
TI  - The metabolic effects of diuretics and other antihypertensive drugs: a
      perspective as of 1989.
AB  - Active treatment has produced a dramatic decline in the 'mechanical'
      complications of hypertension (haemorrhagic stroke, congestive heart failure,
      renal failure, and aortic dissection) but has had no effect on the 'thrombotic'
      complications (thrombotic stroke, and myocardial infarction). There is a growing
      body of opinion that this failure is related to changes in the metabolism of
      lipoproteins and carbohydrates induced by anti-hypertensive drugs, which actively
      counteract the beneficial effects of a lowered blood pressure. The literature on
      this subject is extensive, but the results are inconclusive and much remains to
      be learned. In the light of present knowledge, it would appear to be prudent to
      choose anti-hypertensive drugs with care, concentrating upon proven agents which
      produce minimal biochemical disturbances, rather than using drugs which are known
      to have marked effects on lipoprotein metabolism.

PMID- 1975569
TI  - Comparison of angiographic methods for the assessment of the extent of
      experimental anterior myocardial infarction in dog hearts.
AB  - Infarction was provoked in the dog by introducing a copper coil into the left
      anterior descending coronary artery. Eight groups, each of 6 dogs, were studied
      which received various treatments and were evaluated after 24 hours or 1 week.
      The anatomical extent of infarction was measured by the
      triphenyltetrazoliumhydrochloride method; size was evaluated angiographically by
      the centerline, chord and radial method and by ejection fraction. The extent of
      infarction was similar in groups studied after 24 hours and 1 week.
      Angiographical changes were most marked after 24 hours, and the ejection fraction
      was related to the extent of infarction (r = -0.5; P less than 0.02). Some
      parameters of the radial and centerline method showed also a relation to the
      extent of infarction (r = 0.47 to 0.57; P less than 0.05). After one week, the
      ejection fraction was no longer correlated to the extent of infarction. The
      correlation between the parameters of the chord, radius and centerline method and
      the extent of infarction improved to r-values of 0.58 to 0.63 (P less than or
      equal to 0.01). There was no difference between the 3 methods.

PMID- 1975570
TI  - [Unwanted effects of psychotropic drugs--selected results from a 10-year
      multicenter project monitoring drugs in psychiatry].

PMID- 1975571
TI  - Forskolin and prostaglandin E2 regulate the generation of human cytolytic T
      lymphocytes.
AB  - In this paper we examine the characteristics of human cytolytic T lymphocytes
      (CTL) generated in the presence of forskolin and PGE2. Forskolin and PGE2
      suppressed the generation of class-I-specific CTL. The CTL generated in the
      presence of forskolin and PGE2 had different characteristics which included their
      ability to proliferate in response to the alloantigen and their lectin-mediated
      cytolytic activity. The CTL generated in the presence of forskolin had normal
      proliferative response to the alloantigen, whereas the CTL generated in the
      presence of PGE2 showed a suppressed proliferative ability to the alloantigen.
      The two groups of CTL were then tested for their activity in the process of
      lectin-dependent cell-mediated cytotoxicity. After the addition of PHA into the
      chromium release assay the CTL generated in the presence of forskolin normally
      lysed the nonspecific targets, whereas the CTL generated in the presence of PGE2
      did not show the normal response in lysing the nonspecific targets. The results
      suggest that the cytolytic machinery was intact when the CTL were generated in
      the presence of forskolin but CTL were not able to either recognize or lyse the
      target cell. However, the CTL generated in the presence of PGE2 did not share the
      same characteristics as the CTL generated in the presence of forskolin because
      the CTL generated in the presence of PGE2 were unable to kill even in the
      presence of lectin. It appears that the inhibitory effects of forskolin were
      mediated by cAMP and not by its effects on the potassium channels because the 1,9
      dideoxy derivative of forskolin which did not activate adenylate cyclase also did
      not suppress the generation of CTL. However, it was not established whether the
      diverse effects of PGE2 on the generation of CTL were mediated by cAMP-dependent,
      -independent or by both mechanisms.

PMID- 1975572
TI  - Glutamate-like immunoreactivity in the peripheral vestibular system of mammals.
AB  - Using a specific antibody raised against glutamate (Glu) conjugated to bovine
      serum albumin with glutaraldehyde, the distribution of Glu-like immunoreactivity
      was studied by postembedding staining in semithin sections of nonosmicated or
      osmicated tissue through the vestibular sensory epithelia and ganglia of
      different mammalian species (mouse, rat and cat). Strong immunoreactive staining
      was found in all ganglion neurons and their peripheral and central nerve
      processes as well as in the two types of sensory hair cells whereas, in contrast,
      supporting cells were devoid of immunoreactivity. Glu-like immunoreactivity found
      in vestibular fibers and ganglion neurons, is in good agreement with the
      proposition of glutamate as the neurotransmitter involved in vestibular nerve
      transmission. In sensory hair cells, glutamate, apart from its metabolic
      function, may play a role in synaptic transmission between the sensory cells and
      the vestibular afferent fibers.

PMID- 1975573
TI  - Brain glutamate metabolism during hypoxia and peripheral chemodenervation.
AB  - Glutamate stimulates resting ventilation by altering neural excitability
      centrally. Hypoxia increases central ventilatory drive through peripheral
      chemoreceptor stimulation and may also alter cerebral perfusion and glutamate
      metabolism locally. Therefore the effect of hypoxia and peripheral
      chemodenervation on cerebrospinal fluid (CSF) transfer rate of in vivo tracer
      amidated central nervous system glutamate was studied in intact and
      chemodenervated pentobarbital-anesthetized dogs during normoxia and after 1 h of
      hypoxia induced with 10 or 12% O2 in N2 breathing at constant expired ventilation
      and arterial CO2 tension. Chemodenervation was performed by bilateral sectioning
      of the carotid body nerves and cervical vagi. CSF transfer rates of radiotracer
      13NH4+ and [13N]glutamine synthesized via the reaction, glutamate + NH4(+)---
      glutamine, in brain glia were measured during normoxia and after 1 h of hypoxia.
      At normoxia, maximal glial glutamine efflux rate jm = 103.3 +/- 11.2 (SE) mumol.l
      1.min-1 in all animals. After 1 h of hypoxia in intact animals, jm = 78.4 +/-
      10.0 mumol.l-1.min-1. In denervated animals, jm was decreased to 46.3 +/- 4.3
      mumol.l-1.min-1. During hypoxia, mean cerebral cortical glutamate concentration
      was higher in denervated animals (9.98 +/- 1.43 mumol/g brain tissue) than in
      intact animals (7.63 +/- 1.82 mumol/g brain tissue) and corresponding medullary
      glutamate concentration tended to be higher in denervated animals. There were no
      differences between mean glutamine and gamma-aminobutyric acid
      concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1975574
TI  - Effects on breathing of rostral pons glutamate injection during opossum
      development.
AB  - To determine whether pathways from the rostral pons, capable of influencing
      breathing, were present in immature mammals, the excitatory amino acid glutamate
      (sodium salt) was pressure injected in very small volumes into the rostral pons
      of suckling and adult opossums. The youngest animals tested were approximately 3
      wk old (1.5-2.9 g). Animals were anesthetized with the thiobarbituric acid
      derivative, Inactin, and the electromyogram of the diaphragm was used to assess
      changes in breathing rhythm and ventilatory output. Glutamate concentrations of
      50, 150, and 1,000 mM were injected into the rostral pons. Active sites were
      generally located between parabrachial and either lateral lemniscal or trigeminal
      nuclei. Effects of glutamate in opossums of all ages included changes in
      diaphragm activity and respiratory timing over several breaths. In the youngest
      animals, a very high incidence of apnea occurred as an initial response (17 of 20
      sites) at the 1,000 mM concentration. The high incidence of apneic response in
      the youngest animals suggests that strong activation of rostral pontine neurons
      can more easily disrupt respiratory output; a physiological circumstance of such
      activation might include a diving response stimulated by trigeminal afferents.

PMID- 1975575
TI  - Pulmonary microcirculatory kinetics of neutrophils deficient in leukocyte
      adhesion-promoting glycoproteins.
AB  - The mechanism that causes neutrophils to sequester in the pulmonary circulation
      is unknown. Because the CD11/CD18 glycoprotein family on the surface membrane of
      neutrophils participates in many adhesive interactions with the endothelium, we
      investigated the role of these proteins in the intravascular sequestration of
      pulmonary neutrophils. Neutrophils were isolated from normal dogs and from the
      only living dog known to have leukocyte adhesion deficiency disease, an inherited
      deficiency of the CD11/CD18 adhesion family. The neutrophils were labeled with
      fluorescein dye, injected into normal recipient dogs, and their passage through
      the pulmonary microcirculation was recorded by in vivo videofluorescence
      microscopy through a transparent thoracic window. Transit times for normal and
      deficient neutrophils were similar over a wide range of hemo-dynamic conditions.
      Activation by zymosan-activated plasma, which increases the surface membrane
      expression of CD11/CD18, prolonged the transit of normal neutrophils but did not
      alter the transit time of the deficient neutrophils. These results indicate that
      neutrophil CD11/CD18 adhesion-promoting glycoproteins are not involved in the
      normal pulmonary sequestration of neutrophils but have a significant role in the
      arrest of activated neutrophils in the pulmonary capillaries.

PMID- 1975576
TI  - Endogenous AA metabolites and their possible role in tracheal smooth muscle tone
      in guinea pigs.
AB  - The effects of endogenous arachidonic acid (AA) metabolites on inherent tone and
      histamine-induced constriction were studied in guinea pig tracheal smooth muscle.
      Inhibitors of either cyclooxygenase (indomethacin) or lipoxygenase (AA 861)
      significantly diminished the inherent tone of the muscle. Antagonists of
      prostaglandins (SC 19220) or leukotrienes (FPL 55712) also diminished the
      inherent tone, whereas an inhibitor of thromboxane synthase (OKY 046) had no
      significant effect. These results show that the metabolites of the lipoxygenase
      pathway as well as prostaglandins also participate in the maintenance of inherent
      tone. To reexamine the previously reported augmentation of histamine constriction
      induced by the inhibitors and the antagonists, we compared the active tension of
      the muscle measured from the maximum relaxed level as the base line to eliminate
      the fluctuation of inherent tone. Such comparison revealed that the inhibitors
      and the antagonists have no augmentative effect on either the maximum response to
      histamine or the concentration required to produce 50% of maximum active tension
      and that there is functional synergism between the exogenously added histamine
      and the endogenously produced AA metabolites. Therefore the zero active tension
      is useful as a base line to compare the contractile response of a drug-treated
      preparation with that of a nontreated preparation.

PMID- 1975577
TI  - Isolation and culture of hepatocytes from the cynomolgus monkey (Macaca
      fascicularis).
AB  - Isolation and culture techniques for hepatocytes from whole livers of the
      cynomolgus monkey, Macaca fascicularis, are described. Hepatocytes were isolated
      by two-step perfusion of livers, using collagenase with hyaluronidase; fructose
      and trypsin inhibitor were included to reduce cell loss. Yields from a single
      liver average 4 X 10(9) cells with viabilities of 90.8 +/- 5.7%. Cells, plated on
      collagen substrates, were assessed for changes in morphology and various marker
      enzyme activities over a period of 7 d in culture. Cells exhibited a morphology
      similar to that observed for this species in vivo; little change in attached and
      spread cells was observed over the length of time monitored. Enzyme activities
      for catalase, succinate dehydrogenase, and tyrosine aminotransferase were
      observed to decrease significantly (though considerable activity remained),
      whereas acid phosphatase and 5'-nucleotide phosphodiesterase remained unchanged.
      Activity of cytochrome P-450 reductase was observed to increase slightly for the
      first 2 d, then decrease to about 60% of initial levels. Activity of alpha
      mannosidase was stable for 4 d but was observed to be increased at Day 7. Cells
      were observed to retain metabolic responsiveness, demonstrated by glucose
      production by both gluconeogenesis and glycogenolysis in response to glucagon
      stimulation. The monkey hepatocytes obtained by methods described here thus
      retain hepatocellular morphology and activity through at least 1 wk in culture
      without medium or culture modification.

PMID- 1975578
TI  - Role of NAD-linked glutamate dehydrogenase in nitrogen metabolism in
      Saccharomyces cerevisiae.
AB  - We cloned GDH2, the gene that encodes the NAD-linked glutamate dehydrogenase in
      the yeast Saccharomyces cerevisiae, by purifying the enzyme, making polyclonal
      antibodies to it, and using the antibodies to screen a lambda gt11 yeast genomic
      library. A yeast strain with a deletion-disruption allele of GDH2 which replaced
      the wild-type gene grew very poorly with glutamate as a nitrogen source, but
      growth improved significantly when the strain was also provided with adenine or
      other nitrogenous compounds whose biosynthesis requires glutamine. Our results
      indicate that the NAD-linked glutamate dehydrogenase catalyzes the major, but not
      sole, pathway for generation of ammonia from glutamate. We also isolated yeast
      mutants that lacked glutamate synthase activity and present evidence which shows
      that normally NAD-linked glutamate dehydrogenase is not involved in glutamate
      biosynthesis, but that if the enzyme is overexpressed, it may function reversibly
      in intact cells.

PMID- 1975579
TI  - Isolation and characterization of a Neurospora crassa mutant altered in the alpha
      polypeptide of glutamine synthetase.
AB  - We report the isolation and characterization of a Neurospora crassa glutamine
      synthetase (GS) mutant altered in one of the two polypeptides (GS alpha) of this
      enzyme. We used the gln-1bR8 mutant strain that synthesizes only the GS alpha
      monomer and lacks the GS beta monomer and selected for growth in minimal medium
      in the presence of alpha-methyl-DL-methionine-SR-sulfoximine (alpha-me-MSO), an
      inhibitor of GS activity. The GS activity of the gln-1bR8;alpha-me-MSOR strain
      drastically reduced its transferase activity and only slightly reduced its
      synthetase activity, and it was resistant to inhibition by alpha-me-MSO and L
      methionine-DL-sulfoximine. The mutation that overcame the inhibitory effect of
      alpha-me-MSO also altered the antigenic, kinetic, and physical properties of GS
      alpha. The low GS activity of the alpha-me-MSO-resistant strain was compensated
      for by a higher glutamate/glutamine ratio and a lower glutamate synthase
      activity, allowing this strain to grow as well as the parental strain. The
      mutation that conferred resistance to alpha-me-MSO was not linked to the gln-1bR8
      mutation, providing direct evidence of the existence of two genes involved with
      the structure of the two polypeptides of N. crassa GS.

PMID- 1975580
TI  - Sequence of the Streptococcus pneumoniae bacteriophage HB-3 amidase reveals high
      homology with the major host autolysin.
AB  - We have sequenced a DNA fragment containing the pneumococcal bacteriophage HB-3
      hbl gene, which codes for the phage lytic amidase. A remarkable nucleotide
      similarity (87.1%) between the lytA gene, coding for the pneumococcal amidase,
      the major autolysin of Streptococcus pneumoniae, and the hbl gene was found. This
      similarity completely disappeared outside the open reading frames coding for both
      amidases. The hbl gene transformed amidase-deficient strains of S. pneumoniae to
      the wild-type phenotype, and Southern blotting experiments provided evidence for
      recombination between donor and recipient genes. A comprehensive evaluation of
      these and previous results on the peptidoglycan hydrolases of S. pneumoniae and
      its bacteriophages suggested that recombination mechanisms participate in the
      evolution of the genes coding for these enzymes.

PMID- 1975581
TI  - Regulation and sequence of the Synechococcus sp. strain PCC 7942 groESL operon,
      encoding a cyanobacterial chaperonin.
AB  - The molecular chaperonins such as GroEL are now widely regarded as essential
      components for the stabilization of integral membrane or secretory proteins
      before membrane insertion or translocation, as well as for the assembly of
      macromolecular complexes such as ribulose bisphosphate carboxylase-oxygenase. The
      groESL operon of Synechococcus sp. strain PCC 7942 was cloned as two independent
      lacZ-groEL translational fusions by immunoscreening a lambda ZAP genomic
      expression library and then sequenced. The derived amino acid sequences of the
      GroES and GroEL proteins demonstrated very high levels of amino acid identity
      with cognate chaperonins from bacteria and chloroplasts. The bicistronic 2.4
      kilobase transcript from this operon, barely detectable in RNA preparations from
      cells grown at 30 degrees C, accumulated approximately 120-fold in preparations
      from cells grown for 20 min at 45 degrees C. Under these conditions, GroEL
      protein accumulated to 10-fold-higher levels. Primer extension analysis was used
      to identify a cyanobacterial heat shock promoter located at -81 base pairs from
      the groES initiation codon. The transcriptional -10 and -35 sequences differ
      slightly from Escherichia coli consensus heat shock promoter sequences.

PMID- 1975582
TI  - Use of a wild-type gene fusion to determine the influence of environmental
      conditions on expression of the S fimbrial adhesin in an Escherichia coli
      pathogen.
AB  - S fimbrial adhesins (Sfa) enable pathogenic Escherichia coli strains to bind to
      sialic acid-containing eucaryotic receptor molecules. In order to determine the
      influence of culture conditions on the expression of the sfa determinant in a
      wild-type strain, we fused the gene lacZ, coding for the enzyme beta
      galactosidase, to the sfaA gene, responsible for the major protein subunit of S
      fimbriae. By using a plasmid which carries an R6K origin, the sfaA-lac hybrid
      construct was site-specifically integrated into the chromosome of the
      uropathogenic E. coli strain 536WT. The expression of lacZ, which was under the
      control of the sfa wild-type promoters, was now equivalent to the sfa expression
      of strain 536WT. With the help of this particular wild-type construct, it was
      demonstrated that the sfa determinant is better expressed on solid media than in
      liquid broth. The growth rate had a strong influence on Sfa expression under
      aerobic but not under anaerobic conditions. Production of Sfa was further
      regulated by catabolite repression, osmolarity, and temperature.

PMID- 1975583
TI  - Overexpression of a Streptomyces viridochromogenes gene (glnII) encoding a
      glutamine synthetase similar to those of eucaryotes confers resistance against
      the antibiotic phosphinothricyl-alanyl-alanine.
AB  - Phosphinothricyl-alanyl-alanine (PTT), also known as bialaphos, contains
      phosphinothricin, a potent inhibitor of glutamine synthetase (GS). A 2.75
      kilobase NcoI fragment of the Streptomyces viridochromogenes PTT-resistant mutant
      ES2 cloned on a multicopy vector mediated PTT resistance to S. lividans and to S.
      viridochromogenes. Nucleotide sequence analysis of the 2.75-kb NcoI fragment
      revealed the presence of three open reading frames. Open reading frame 3 was
      termed glnII since significant similarity was found between its deduced amino
      acid sequence and those from GS of eucaryotes and GSII of members of the family
      Rhizobiaceae. Subcloning experiments showed that PTT resistance is mediated by
      overexpression of glnII encoding a 37.3-kilodalton protein of 343 amino acids. A
      three- to fourfold increase in gamma-glutamyltransferase activity could be
      observed in S. lividans transformants carrying the glnII gene on a multicopy
      plasmid. For S. viridochromogenes it was shown that PTT resistance conferred by
      the 2.75-kb NcoI fragment was dependent on its multicopy state. GS activity
      encoded by glnII was found to be heat labile. Southern hybridization with seven
      different Streptomyces strains suggested that they all carry two types of GS
      genes, glnA and glnII.

PMID- 1975584
TI  - Molecular cloning, sequencing, and expression of the glutamine synthetase II
      (glnII) gene from the actinomycete root nodule symbiont Frankia sp. strain CpI1.
AB  - In common with other plant symbionts, Frankia spp., the actinomycete N2-fixing
      symbionts of certain nonleguminous woody plants, synthesize two glutamine
      synthetases, GSI and GSII. DNA encoding the Bradyrhizobium japonicum gene for
      GSII (glnII) hybridized to DNA from three Frankia strains. B. japonicum glnII was
      used as a probe to clone the glnII gene from a size-selected KpnI library of
      Frankia strain CpI1 DNA. The region corresponding to the Frankia sp. strain CpI1
      glnII gene was sequenced, and the amino acid sequence was compared with that of
      the GS gene from the pea and glnII from B. japonicum. The Frankia glnII gene
      product has a high degree of similarity with both GSII from B. japonicum and GS
      from pea, although the sequence was about equally similar to both the bacterial
      and eucaryotic proteins. The Frankia glnII gene was also capable of complementing
      an Escherichia coli delta glnA mutant when transcribed from the vector lac
      promoter, but not when transcribed from the Frankia promoter. GSII produced in E.
      coli was heat labile, like the enzyme produced in Frankia sp. strain CpI1 but
      unlike the wild-type E. coli enzyme.

PMID- 1975587
TI  - Functional reassembly of the coated vesicle proton pump.
AB  - We have shown previously that treatment of the coated vesicle proton
      translocating adenosine triphosphatase (H(+)-ATPase) with chaotropic agents
      results in the release of a set of peripheral polypeptides which includes the 73
      , 58-, 40-, 34-, and 33-kDa subunits (Adachi, I., Puopolo, K., Marquez-Sterling,
      N., Arai, H., and Forgac, M. (1990) J. Biol. Chem. 265, 967-973), with a
      coordinate loss of H(+)-ATPase activity. In the present paper we report the
      functional reassembly of the coated vesicle proton pump following dissociation of
      the peripheral subunits. Reassembly was demonstrated by restoration of ATP-driven
      proton transport using both native membranes and reconstituted vesicles and by
      Western blot analysis using a monoclonal antibody specific for the 73-kDa
      subunit. Reassembly occurs by attachment of a peripheral subcomplex containing
      the 73-, 58-, 34-, and 33-kDa subunits together with the 40-kDa polypeptide. The
      reassembled H(+)-ATPase, like the native proton pump, is inhibited by N
      ethylmaleimide, 7-chloro-4-nitrobenz-2-oxa-1,3-diazole, and N,N'
      dicyclohexylcarbodiimide. Reassociation shows a biphasic time dependence, with
      restoration of 50-60% of the starting proton transport activity in the 1st h
      followed by recovery of a further 20-30% of the activity after 24 h. Reassembly
      also shows a marked dependence on protein concentration but, unlike
      solubilization of the intact H(+)-ATPase complex, does not require the presence
      of glycerol. Despite the ability of nucleotides to promote dissociation of the
      peripheral complex by chaotropic agents, reassociation is not blocked by the
      presence of 1 mM ATP. These results thus provide the first evidence for
      functional reassembly of a vacuolar H(+)-ATPase complex and should be useful in
      further analysis of the role of individual subunits in the assembly and activity
      of these ATP-driven proton pumps.

PMID- 1975586
TI  - The carboxyl region contains the catalytic domain of the membrane form of
      guanylate cyclase.
AB  - A polypeptide containing the catalytic domain of an atrial natriuretic peptide
      receptor guanylate cyclase has been produced using a bacterial expression system.
      A carboxyl fragment of the membrane form of guanylate cyclase from rat brain,
      which contains a region homologous to soluble guanylate and adenylate cyclases,
      was expressed in Escherichia coli with a double plasmid system that encodes T7
      RNA polymerase (Tabor, S., and Richardson, C.C. (1985) Proc. Natl. Acad. Sci. U.
      S. A. 82, 1074-1078). Application of this expression system permitted exclusive
      radiolabeling of the cloned gene product, thereby providing a means to evaluate
      the level of expression and stability of encoded proteins. Fusion proteins were
      formed with the T7 bacteriophage gene 10 product and the 293 carboxyl-terminal
      residues of guanylate cyclase and two deletional mutants encoding 105 and 69
      residues. Extracts prepared from bacteria expressing the carboxyl region, but not
      those expressing further deletions in this region, had substantial guanylate
      cyclase activity. There was no associated adenylate cyclase activity, suggesting
      that the catalytic domain retained its enzymatic specificity. These results
      provide direct evidence that the carboxyl portion of the membrane form of
      guanylate cyclase contains a catalytic domain. Homologous regions of the soluble
      form of guanylate cyclase and adenylate cyclase are likely to have enzymatic
      properties.

PMID- 1975585
TI  - Streptomyces hygroscopicus has two glutamine synthetase genes.
AB  - Streptomyces hygroscopicus, which produces the glutamine synthetase inhibitor
      phosphinothricin, possesses at least two genes (glnA and glnB) encoding distinct
      glutamine synthetase isoforms (GSI and GSII). The glnB gene was cloned from S.
      hygroscopicus DNA by complementation in an Escherichia coli glutamine auxotrophic
      mutant (glnA). glnB was subcloned in Streptomyces plasmids by insertion into
      pIJ486 (pMSG3) and pIJ702 (pMSG5). Both constructions conferred resistance to the
      tripeptide form of phosphinothricin (bialaphos) and were able to complement a
      glutamine auxotrophic marker in S. coelicolor. Sodium dodecyl sulfate
      polyacrylamide gel electrophoretic analysis of S. lividans(pMSG5) revealed a
      highly overexpressed 40-kilodalton protein. When GS was purified from this
      strain, it was indistinguishable in apparent molecular mass from the 40
      kilodalton protein. The nucleic acid sequence of the cloned region contained an
      open reading frame which encoded a protein whose size, amino acid composition,
      and N-terminal sequence corresponded to those of the purified GS. glnB had a high
      G + C content and codon usage typical of streptomycete genes. A comparison of its
      predicted amino acid sequence with the protein data bases revealed that it
      encoded a GSII-type enzyme which had previously been found only in various
      eucaryotes (47 to 50% identity) and nodulating bacteria such as Bradyrhizobium
      spp. (42% identity). glnB had only 13 to 18% identity with eubacterial GSI
      enzymes. Southern blot hybridization experiments showed that sequences similar to
      glnB were present in all of the five other Streptomyces species tested, as well
      as Frankia species. These results do not support the previous suggestion that
      GSII-type enzymes found in members of the family Rhizobiaceae represent a unique
      example of interkingdom gene transfer associated with symbiosis in the nodule.
      Instead they imply that the presence of more than one gene encoding GS may be
      more common among soil microorganisms than previously appreciated.

PMID- 1975588
TI  - Constitutive and glucocorticoid-mediated activation of glutamine synthetase gene
      expression in the developing chicken retina.
AB  - This report correlates constitutive and glucocorticoid-mediated alterations in
      glutamine synthetase gene expression observed in chicken retinal organ cultures
      with activation of the gene during terminal differentiation. Because
      glucocorticoid hormones are potent inducers of glutamine synthetase in embryonic
      retinae, they have been considered as primary mediators of the developmental
      rise. However, unlike what might be expected of a developmental inducer, our data
      demonstrate that glucocorticoids act as reversible regulators of glutamine
      synthetase transcription. Moreover, long-term organ culture of embryonic retina
      in the absence of glucocorticoids leads to a dramatic increase in expression of
      glutamine synthetase mRNA. These studies argue that although glucocorticoids may
      potentiate transcription of glutamine synthetase, the retina has been programmed
      as early as embryonic day 6 to express this enzyme at a later time via a
      glucocorticoid-independent process. Interestingly, transcription of retinal
      glutamine synthetase increases by only approximately 10-fold during development,
      based on nuclear run-on measurements. Therefore, post-transcriptional control
      mechanisms might also contribute to the 130-fold increase in glutamine synthetase
      mRNA observed during terminal differentiation.

PMID- 1975589
TI  - Structure of the human laminin B1 chain gene.
AB  - The exon-intron structure of the human laminin B1 chain gene was determined from
      genomic clones that spanned 90 kilobase pairs (kb), including 80 kb of the
      structural gene, about 1 kb of the 5'-flanking region, and 9 kb of the 3'
      flanking region. DNA sequencing and heteroduplex analyses demonstrated that the
      gene consists of 34 exons. The intron sizes vary from 92 base pairs to more than
      15,000 base pairs. The clones did not completely contain introns 13 and 14 and,
      therefore, the exact size of the gene remains to be determined. The first exon
      encodes a 5'-untranslated region, with the ATG translation start codon being in
      exon 2. The promoter region does not contain TATA or CAAT boxes, but it has four
      GC boxes. Additionally, two GC boxes are located in the 5'-untranslated sequence.
      A glucocorticoid response element-like sequence and a sequence resembling the
      binding sequence for transcription factor AP-2 are present in the 5'-flanking
      region. Another potential AP-2 binding sequence is located in the 5'-untranslated
      sequence of exon 1. A TGACC motif present in the binding region for the retinoic
      acid response element of the mouse laminin B1 gene promoter is also present in
      the human counterpart. The overall exon pattern of the gene correlates only
      slightly with the highly conserved structural domains and internal repeats of the
      B1 polypeptide chain. Furthermore, the exon profile differs considerably from
      that of the laminin B2 gene. A HincII/HpaI restriction fragment length
      polymorphism was identified in exon 31.

PMID- 1975590
TI  - Class F Thy-1-negative murine lymphoma cells are deficient in ether lipid
      biosynthesis.
AB  - The glycosyl phosphatidylinositol (PI) membrane anchors of several proteins
      contain 1-alkyl-2-acyl-glycerophosphoinositol. Although this PI analog has never
      been found free in cells, the presence of "alkyl-PI" as a component of some
      membrane anchors suggests its existence. The resistance of ether linkages to
      cleavage by mild alkali treatment was used to detect possible alkyl chains in the
      [3H]inositol-labeled phospholipids of several murine lymphoma cell lines which
      normally express the glycosyl PI-anchored protein Thy-1. One lipid, which arose
      from alkaline hydrolysis of PI and had mobility on thin layer chromatography
      similar to lyso-PI, was detected in all wild-type cell lines. Analysis of the
      base-stable inositol lipids of several lymphoma lines that are deficient in Thy-1
      surface expression because of defective biosynthesis of the glycosyl PI membrane
      anchor revealed that the putative alkyl-PI was missing in the class F mutant. The
      levels of both the ethanolamine- and choline-containing plasmalogens were also
      decreased 10-fold in these cells, suggesting a general defect in the production
      of ether lipids. The activity of the peroxisomal form of
      dihydroxyacetonephosphate acyltransferase, which catalyzes the first step of
      ether lipid biosynthesis, was found to be 10-fold decreased relative to the wild
      type level. Unlike previously described Chinese hamster ovary cell mutants
      deficient in ether lipids (Zoeller, R. A., and Raetz, C. R. H. (1986) Proc. Natl.
      Acad. Sci. U. S. A. 83, 5170-5174), the class F Thy-1- cells contain intact
      functional peroxisomes. Attempts to restore the putative alkyl-PI to the class F
      mutants by alkylglycerol supplementation were unsuccessful, despite concomitant
      restoration of the much larger plasmenylethanolamine pool, suggesting that there
      are some differences in the biosynthesis of this PI analog and plasmalogens that
      are presently not understood. Although the deficiencies in ether lipids and
      surface expression of Thy-1 in the class F mutants could also be due to separate
      mutations, our findings raise the possibility that alkyl-PI exists in animal
      cells and may be an obligate precursor for the biosynthesis of the glycosyl-PI
      membrane anchor of Thy-1.

PMID- 1975591
TI  - Quantitative analysis of the endocytic system involved in hormone-induced
      receptor internalization.
AB  - We have developed a quantitative method to evaluate the interaction between cell
      surface receptors and the endocytic apparatus. This method exploits occupancy
      dependent changes in internalization rates that occur in cells expressing high
      numbers of receptors. We found that constitutive internalization of the
      transferrin receptor behaves as a simple, first order process that is unaltered
      by ligand. Internalization of the epidermal growth factor (EGF) receptor,
      however, behaves as a saturable, second order process that is induced by receptor
      occupancy. Internalization of EGF receptors occurs through at least two distinct
      pathways: a low capacity pathway that has a relatively high affinity for occupied
      receptors, and a low affinity pathway that has a much higher capacity. The high
      affinity pathway was observed in all cells having receptors with intrinsic
      tyrosine kinase activity. Mutant EGF receptors lacking kinase activity could not
      utilize the high affinity pathway and were internalized only through the low
      affinity one. Mutated receptors with decreased affinity for kinase substrates
      were also internalized at decreased rates through the high affinity, inducible
      pathway. In the case of vitellogenin receptors in Xenopus oocytes, occupied
      receptors competed more efficiently for internalization than empty ones. Insulin
      increased the endocytic capacity of oocytes for vitellogenin receptors.
      Similarly, serum increased the capacity of the inducible pathway for EGF
      receptors in mammalian cells. These data are consistent with a model of
      internalization in which occupied receptors bind to specific cellular components
      that mediate rapid internalization. Ligand-induced internalization results from
      an increase in the affinity of occupied receptors for the endocytic apparatus.
      Hormones can also indirectly regulate endocytosis by increasing the number of
      coated pits or their rate of internalization. The ability to dissect receptor
      specific effects from cell-specific ones should be very useful in investigating
      the molecular mechanisms of receptor mediated endocytosis.

PMID- 1975592
TI  - Enhanced phosphorylation of a coated vesicle polypeptide in response to insulin
      stimulation of rat adipocytes.
AB  - The effect of insulin to increase the cell surface concentration of various
      receptors is accompanied by an increase in the concentration of clathrin
      assembled on the plasma membrane (Corvera, S. (1990) J. Biol. Chem. 265, 2413
      2416). In the present study, clathrin-coated membranes were purified from
      isolated adipocytes labeled isotopically with [32P]orthophosphate. Analysis of
      the coated vesicle preparation by polyacrylamide gel electrophoresis and
      autoradiography revealed the presence of a cluster of phosphopeptides of 90-100
      kDa as well as other phosphorylated species of 125, 70, 58, 50, 43, and 32 kDa.
      Incubation of the coated vesicles in alkaline pH resulted in the elution of the
      majority of the phosphopeptides, suggesting that these components are part of the
      clathrin coat and not integral membrane proteins. A pronounced increase in the
      amount of phosphate incorporated into the 125-kDa species was observed in
      response to stimulation of labeled cells by low concentrations of insulin.
      Phosphoamino acid analysis of an acid hydrolysate of this band revealed that its
      phosphorylation occurred exclusively on serine residues. The increased serine
      phosphorylation of this protein was apparent after only 2 min of exposure of
      cells to insulin and persisted for at least 60 min. The effect of insulin to
      increase the cell surface concentration of receptors and the assembly of clathrin
      on the plasma membrane displays a similar time course. Phorbol esters or
      dibutyryl cyclic AMP did not mimic the effects of insulin to stimulate the
      incorporation of [32P]phosphate into the 125-kDa polypeptide. Phosphorylation of
      the 125-kDa polypeptide was not observed after incubation of purified adipocyte
      coated vesicles with [gamma-32P]ATP, suggesting that the kinase responsible for
      this reaction may not be contained within the clathrin-coated vesicle itself.
      These results suggest that phosphorylation of this 125-kDa polypeptide in intact
      cells may play a role in the regulation of clathrin-coated membrane formation and
      receptor-mediated endocytosis in response to insulin.

PMID- 1975594
TI  - Elevated levels of CD4 antigen in sera of human immunodeficiency virus-infected
      populations.
AB  - CD4 antigen levels in sera from asymptomatic intravenous drug users and
      homosexuals and patients with lymphadenopathy, acquired immunodeficiency syndrome
      related complex, or acquired immunodeficiency syndrome were quantitated. Like
      soluble CD8, CD4 antigen levels were elevated in human immunodeficiency virus
      seronegative asymptomatic intravenous drug users and homosexuals, probably
      reflecting infections such as cytomegalovirus, Epstein-Barr virus, and hepatitis
      B virus infections. The sera from human immunodeficiency virus-seropositive
      groups of patients with human immunodeficiency virus infection also had elevated
      levels of CD4 antigen, presumably reflecting infections like cytomegalovirus and
      human immunodeficiency virus infections.

PMID- 1975593
TI  - Characterization of epidemic and nonepidemic Neisseria meningitidis serogroup A
      strains from Sudan and Sweden.
AB  - A random selection of 25 strains isolated during an epidemic caused by serogroup
      A Neisseria meningitidis in Sudan (1988), 3 preepidemic meningococcal strains
      (1985), and 26 serogroup A strains isolated from sporadic cases of meningitis in
      Sweden (1973 to 1987) were assessed for multilocus enzyme genotypes (ETs), DNA
      restriction enzyme patterns, outer membrane proteins, lipopolysaccharides, pilus
      formation, and antibiograms. All of the 25 Sudanese epidemic isolates and 22 of
      the Swedish strains were of the same or closely related ETs (ETs 3, 4, and 5),
      corresponding to clone III-1, which has been responsible for two pandemic waves
      in the last three decades. The earlier pandemic involved Scandinavia, and the
      last one caused an outbreak during the pilgrimage to Mecca, Saudi Arabia (August
      1987), spreading to Sudan, Chad, and Ethiopia. The three Sudanese preepidemic
      isolates (1985) were clone IV-1 (sulfonamide susceptible), which has been
      resident in the African meningitis belt for the last 25 years. The uniformity of
      clone III-1 strains (all sulfonamide resistant) from Sudan and Sweden was
      confirmed by DNA restriction enzyme patterns. ETs 3, 4, and 5 from Sudan and
      Sweden had 86 to 100% similarity to a Swedish clone III-1 reference strain,
      whereas ETs 1, 2, 6, and 7 showed 50 to 80% similarity. Class 1 protein for clone
      III-1 showed serosubtype antigens P1.9 and P1.x, whereas ET6 strains (clone IV-1)
      had serosubtype P1.7. Lipopolysaccharides were variable in the Sudanese and
      Swedish strains. Pili were expressed in all clone III-1 isolates from Sudan and
      Sweden but in none of the clone IV-1 isolates (Sudan, 1985).

PMID- 1975595
TI  - Pneumocystis carinii karyotypes.
AB  - Pulsed-field gel electrophoresis techniques were used to examine the chromosomes
      of Pneumocystis carinii isolated from laboratory rats and two human subjects. P.
      carinii organisms isolated from each of four rat colonies and from two patients
      each produced a distinct band pattern, but in all cases the bands ranged in size
      from 300 to 700 kilobase pairs. P. carinii from three rat colonies produced
      patterns containing 15 prominent bands. Of these 15 bands, 2 stained more
      intensely than would be expected of bands of their size, suggesting that the P.
      carinii haploid genome contains 17 to 19 chromosomes. Summing the molecular sizes
      of the bands and accounting for staining intensities suggested that the haploid
      genome of rat-derived P. carinii contains on the order of 10(7) base pairs. Human
      derived P. carinii produced patterns containing 10 to 12 bands which appeared to
      be similar to the 15-band patterns seen in rat-derived P. carinii with respect to
      the size range of the bands. P. carinii from the fourth rat colony produced a
      more complex band pattern containing approximately 22 bands, most of which
      appeared to comigrate with the bands present in one of the 15-band P. carinii
      patterns, suggesting that these animals were simultaneously infected by two
      different varieties of P. carinii. Hybridization experiments using
      oligonucleotide probes specific for the P. carinii 18S rRNA gene supported this
      possibility. The band pattern of P. carinii derived from a given rat colony was
      generally stable over time. P. carinii band patterns were not strictly rat strain
      specific and appeared to be transferrable between animals housed in the same
      room.

PMID- 1975596
TI  - Evidence for a group-specific enteroviral antigen(s) recognized by human T cells.
AB  - Human peripheral blood mononuclear cells from 15 normal, healthy adult volunteers
      proliferated in vitro against a panel of enteroviral antigens, including
      coxsackievirus B3, coxsackievirus B2, coxsackievirus B6, coxsackievirus A16, and
      poliovirus 1. No proliferation against the cardiovirus encephalomyocarditis virus
      occurred. Lymphocytes obtained from cord blood drawn from seven neonates were
      uniformly nonresponsive to enteroviral antigens. Although serum neutralization
      antibody titers indicated different exposure histories of the volunteers, only
      one had a titer against coxsackievirus B6, a rare isolate in the United States.
      The peripheral blood mononuclear cells from each volunteer responded in vitro to
      each enterovirus tested even though not all individuals had serum neutralizing
      antibody against each virus. The predominant cell type responding in vitro was
      the CD4+ T cell. Denaturation of viral antigen by Formalin did not prevent the
      recognition of the common group antigen by the T cells, indicating that
      noninfectious virus can also serve as antigen. These data demonstrate that human
      T cells recognize a common enterovirus group antigen(s).

PMID- 1975597
TI  - A missense mutation at codon 188 of the human lipoprotein lipase gene is a
      frequent cause of lipoprotein lipase deficiency in persons of different
      ancestries.
AB  - Lipoprotein lipase (LPL) plays a crucial role in the regulation of lipoprotein
      metabolism by hydrolysing the core triglycerides of circulating chylomicrons and
      VLDL. Human, bovine, mouse, and guinea pig complementary DNA clones have recently
      been isolated and the organization of the human LPL gene is now known to comprise
      10 exons spanning approximately 30 kb. Here we report a similar mutation on 21
      alleles from 13 unrelated affected probands with LPL deficiency of French
      Canadian, English, Polish, German, Dutch, and East Indian ancestry. We show that
      an identical missense mutation within exon 5, resulting in an amino acid
      substitution of glutamic acid for glycine at position 188, is responsible for LPL
      deficiency in 21 of 88 LPL alleles assessed. This mutation alters an Ava II
      restriction site in exon 5 and will allow a rapid screening test for this
      mutation in patients with LPL deficiency. This mutation has occurred on the same
      haplotype in all the unrelated affected persons suggesting a common origin. The
      amino acid substitution lies within the longest segment of homology for LPL in
      different species and results in a protein that is catalytically defective.

PMID- 1975598
TI  - Point mutation in the beta-spectrin gene associated with alpha I/74 hereditary
      elliptocytosis. Implications for the mechanism of spectrin dimer self
      association.
AB  - alpha I/74 hereditary elliptocytosis (HE) is a subgroup of HE in which patients
      exhibit an impaired self-association of spectrin dimers and an abnormal
      proteolytic cleavage of the alpha I domain of spectrin. We studied a family in
      which the proband presented with a severe neonatal hemolytic anemia with
      poikilocytosis. Biochemical analysis of erythrocytes from the proband and his
      family members allowed us to ascertain a diagnosis of homozygosity for alpha I/74
      HE in the proband and heterozygosity in his parents and several of their
      offspring. Results of polymorphism linkage analysis suggested that the defect in
      this family was located in beta rather than alpha spectrin. We analyzed the 3'
      end of the beta-spectrin gene of the proband and detected a mutation that changes
      a codon for alanine to one for proline. Allele-specific oligomer hybridization on
      slot blots of DNA from other family members confirmed the presence of the
      mutation only in members heterozygous for the disorder. This is the first example
      of a point mutation in the beta-spectrin chain that is associated with defective
      spectrin dimer self-association and an abnormal proteolytic cleavage of the alpha
      chain. Based on this finding, we propose a model for the mechanism of interaction
      between the alpha- and beta-spectrin chains.

PMID- 1975599
TI  - Familial hypertrophic cardiomyopathy is a genetically heterogeneous disease.
AB  - We demonstrate that familial hypertrophic cardiomyopathy (FHC), an autosomal
      dominant disorder of heart muscle, is a genetically heterogeneous disease. The
      locus responsible for FHC in members of one large kindred was recently mapped to
      chromosome 14q11-12 (FHC-1). We have characterized three additional unrelated
      families in which the gene for FHC segregates as an autosomal dominant trait to
      determine if these disease loci also map to FHC-1. All family members were
      clinically studied by physical examination, electrocardiogram, and two
      dimensional echocardiography. Genetic studies were performed using DNA probes
      which are derived from loci that are closely linked to FHC-1. In one family the
      genetic defect maps to the previously identified FHC-1 locus. However, the loci
      responsible for FHC in two other families were not linked to FHC-1. We conclude
      that FHC can be caused by defects in at least two loci and is a genetically
      heterogeneous disorder.

PMID- 1975600
TI  - Factor XIIIa in fibrovascular tumors.

PMID- 1975601
TI  - Not all spindled-shaped cells embedded in a collagenous stroma are fibroblasts:
      recognition of the "collagen-associated dendrophage".

PMID- 1975602
TI  - 1st L. H. Gray Workshop. Measurement of radiation-induced damage.

PMID- 1975603
TI  - Yields of radiation-induced base products in DNA: effects of DNA conformation and
      gassing conditions.
AB  - Gas chromatography-mass spectrometry with selected-ion monitoring was used to
      measure the yields of radiation-induced base products in aqueous solutions of
      native or heat-denatured DNA irradiated in the dose range 20-100 Gy. These DNA
      solutions were saturated with nitrous oxide, nitrogen, air or 20% oxygen in
      nitrous oxide during irradiation. The products measured were as follows: 5,6
      dihydrothymine; 5-hydroxy-5,6-dihydrothymine; 5,6-dihydrothymine (thymine
      glycol); 5-hydroxy-5,6-dihydrocytosine; 5,6-dihydroxy-5,6- dihydrocytosine
      (cytosine glycol); 4,6-diamino-5-formamidopyrimidine; 7,8-dihydro-8-oxoadenine (8
      hydroxyadenine); 2,6-diamino-4-hydroxy-5- formamidopyrimidine; and 7,8-dihydro-8
      oxoguanine (8-hydroxyguanine). In oxygenated solutions, 5,6-dihydrothymine, 5
      hydroxy-5,6-dihydrothymine and 5-hydroxy-5,6-dihydrocytosine were not formed. The
      yields of all products, other than 5,6-dihydrothymine, were greater in irradiated
      DNA samples from N2O-saturated solutions than from N2-saturated solutions. In N2
      saturated solutions the yield of 8-hydroxyadenine was low and 8-hydroxyguanine
      was undetectable. Yields of pyrimidine products in heat-denatured DNA were
      greater than those in native DNA using all types of gases. However, the effects
      of DNA conformation on the yields of purine products were dependent on the type
      of gas used to saturate the irradiated DNA solutions. Yields of
      formamidopyrimidines were generally lower in solutions of DNA irradiated in the
      native than in the heat-denatured conformation. In air-saturated solutions of
      DNA, yields of 8-hydroxypurines were not influenced greatly by DNA conformation.
      In DNA solutions saturated with N2O/O2, 8-hydroxypurine formation was more
      favourable in the heat-denatured conformation than in the native conformation. On
      the other hand, in deoxygenated solutions, formation of 8-hydroxypurines was
      favoured in the native conformation. Data indicate that DNA conformation and the
      type of gas used to saturate the irradiated solutions have a profound influence
      on yields of base products in DNA.

PMID- 1975604
TI  - Correlation between non-repairable DNA lesions and fixation of cell damage by
      hypertonic solutions in Chinese hamster cells.
AB  - In Chinese hamster HA-1 cells, killing induced by gamma-rays was enhanced by post
      irradiation treatment with hypertonic solution (0.5 mol/l NaCl in phosphate
      buffered saline, pH 7.2) for 20 min. The initial DNA double-strand breaks (dsb)
      induced by gamma-rays were repaired during post-irradiation treatment with
      hypertonic solution. However, hypertonic treatment following gamma-irradiation
      enhanced the frequency of non-repairable dsb, as compared with the frequency
      after incubation at 37 degrees C following gamma-irradiation. Hypertonic
      treatment did not affect the initial half-time for rejoining of dsb. Hypertonic
      treatment did not enhance cell killing, nor did it enhance the non-repairable dsb
      when the irradiated cells were incubated at 37 degrees C for 2 h. These results
      suggest that fixation of gamma-ray-induced potentially lethal damage by
      hypertonic treatment results from inhibition of the rejoining of dsb.

PMID- 1975605
TI  - The relationship of DNA double-strand break induction to radiosensitivity in
      human tumour cell lines.
AB  - Recent data suggest that the differences in radiosensitivity between cell lines
      can be related to differences in dsb induction (Radford 1986a). In the light of
      this we have set out to assess the extent to which differences in radiation
      survival between human tumour cell lines can be attributed to differences in dsb
      induction. For nine human tumour lines survival was assayed by clonogenic assay
      and compared with dsb induction by irradiation at ice-bath temperature as
      measured by neutral filter elution. The lines varied widely in their sensitivity,
      ranging from a sensitive neuroblastoma (surviving fraction at 2 Gy, SF2 = 0.13)
      to a resistant bladder carcinoma (SF2 = 0.62). Dsb induction was found to vary
      between the cell lines, such that resistant cells generally suffered less damage
      than sensitive ones. However, the relationship between damage induction and
      cellular sensitivity was not a simple one, and other factors which may influence
      sensitivity need to be invoked. These data suggest that, in human tumour cell
      lines, differences in radiosensitivity may at least in part be due to different
      levels of damage induction, but that some lines may vary in their tolerance of
      damage due to differences in biological characteristics such as repair capacity.

PMID- 1975606
TI  - ESR study of the thymine anion radical in a single crystal of thymine
      monohydrate.
AB  - ESR spectroscopy was used to study free radicals in an irradiated single crystal
      of thymine monohydrate at 77 K. At low microwave power (20 microW), a broad
      doublet is found to be super-imposed on the well known resonance patterns of the
      5-yl and 7-yl radicals. The doublet spectrum has been analysed as a difference
      spectrum. Its spectroscopic properties and the observed transformation into the 5
      yl, H-addition radical on warming the crystal are consistent with its anion
      nature, T(-).

PMID- 1975607
TI  - Superoxide dismutase and media dependence of far-UV radiation resistance in thiol
      treated cells.
AB  - Pretreatment of wild-type Escherichia coli K12 cells with dithiothreitol (DTT)
      induces far-UV radiation resistance after the thiol is removed (Claycamp 1988).
      The present study shows that a 1 h treatment of cells with DTT in minimal medium
      followed by a 0.5 h incubation in buffer (37 degrees C) results in a dose
      reduction factor (DRF) calculated at F37 of 1.81. When the thiol pretreatment was
      in rich medium, sensitization occurs with DRF = 0.729. This sensitization could
      be reversed to protection by inhibiting extracellular thiol oxidation in rich
      medium with the chelator, DETAPAC, such that the thiol oxidation rate was
      equivalent to that of DTT in minimal medium. Both thiol-induced resistance and
      sensitization produced changes predominantly in the shoulders of the survival
      curves. Furthermore, for either protection or sensitization, at least one form of
      endogenous superoxide dismutase (SOD) was required: in SOD-deficient cells
      (sodAsodB) the DRFs were 1.08 and 0.882 for minimal and rich media, respectively.
      These results suggest that different targets are involved in thiol-induced UV
      protection and sensitization: DNA and extracellular targets (e.g. the membrane),
      respectively. The results augment observations of alternate and multiple repair
      pathways inducible by oxygen radicals and may help understanding non
      physicochemical thiol protection mechanisms.

PMID- 1975608
TI  - Dose-dependent effects of ionizing radiation on in vitro myoblast fusion.
AB  - We have recently demonstrated by dielectric relaxation studies in the radio
      frequency range that there is a sharp decrease in the conductivity and
      permittivity of the membranes of chick embryo myoblasts in vitro at the time of
      fusion (60 h) (Bonincontro et al. 1987). This sharp fall in membrane electrical
      parameters was subsequently shown to be due to changes in ionic flux,
      particularly of the Na+/K+ equilibrium (Santini et al. 1988). Ionizing radiation
      induces a wide variety of effects on biological membranes, including variations
      in membrane ionic transport. We wished to investigate if sublethal doses of gamma
      irradiation could affect membrane electrical parameters and thus myoblast
      membrane fusion. Consequently, chick embryo myoblast aggregate cultures were
      irradiated with 3.25, 5.15 or 6.35 Gy at 24 h of culture. We found that the lower
      dose delays membrane fusion by about 10 h while the two higher doses block fusion
      up to 120 h of culture. Aggregates showed a very high cell viability. The
      possible mechanisms by which ionizing radiation causes these variations in
      myoblast membrane electrical properties and fusion are discussed.

PMID- 1975609
TI  - Cellular inhibition of microtubule assembly by photoactivated sulphonated meso
      tetraphenylporphines.
AB  - This work relates to studies on modes of phototoxicity by sulphonated
      mesotetraphenylporphines on cultured cells. Toxicity appears to be related to
      inhibition of microtubule function. Treatment of human cervix carcinoma cells of
      the line NHIK 3025 incubated for 18 h with meso-tetraphenylporphine sulphonates
      (TPPSn where n = 2a, 2o or 4) and exposed to light, inhibits multiplication for
      the first hours after light exposure, a significant fraction of the cells
      accumulating in mitosis. The maximal number of cells in mitosis after treatment
      (approximately 20%) is dependent on the fluence but is similar for all three
      photosensitizers. For the first hours after treatment the mitotic cells were
      always mainly in metaphase; mainly seen as c-metaphases and three-group
      metaphases. During this time anaphase and telophase cells were absent or greatly
      reduced in number. Indirect immunofluorescence staining of beta-tubulin showed
      that the spindle apparatus of mitotic cells was perturbed in all cases. Results
      are presented which indicate that photoactivation of TPPSn located on the plasma
      membrane destroys microtubules in interphase cells and leads to arrest of the
      cells in mitosis. The localization of the dye which sensitizes the photoinduced
      perturbation of microtubules is further discussed.

PMID- 1975610
TI  - Repair of radiation-induced chromatid aberrations: relationship to G2 arrest in
      CHO cells.
AB  - The literature suggests that the function of radiation-induced G2 arrest is to
      allow repair of potentially lethal damage before cell-entry into, and damage
      expression in, mitosis. The nature of the damage repaired is not known, but
      chromosome aberrations have been considered. To examine this possibility in G2
      cells, the rate of repair of chromatid aberrations in CHO cells progressing to or
      arrested in G2 was compared with the rate of repair of the damage which gives
      rise to G2 arrest. To measure aberration repair rates, exponentially growing CHO
      cells arrested in G2 with 1.5, 2.5 or 3.5 Gy of X-rays were released into mitosis
      by treatment with 5 mM caffeine immediately or 1, 2 or 3 h after irradiation.
      Aberration frequencies in these cells were then related to the caffeine-free
      (repair) interval. To measure the rate of repair of arrest-causing damage a split
      dose procedure was used. The half-times for aberration repair were approximately
      1 h for achromatic gaps and 1.5 h for breaks, intrachanges and interchanges. The
      half-time for arrest damage repair varied with radiation dose. This result
      suggests that chromatid aberrations are not a primary cause of radiation-induced
      G2 arrest.

PMID- 1975611
TI  - Thickness measurements on V79-4 cells: a comparison between laser scanning
      confocal microscopy and electron microscopy.
AB  - A quantitative comparison has been carried out between laser scanning confocal
      microscopy on living cells and standard electron microscope methods on fixed
      samples. It was estimated from these measurements that there was about 10-20%
      reduction in thickness in fixed samples of monolayer V79-4 hamster cells. Precise
      information on the true thickness of living cells, as irradiated, is required for
      full interpretation of radiobiological data with poorly penetrating radiations,
      including ultrasoft X-rays. The confocal microscope allows rapid measurements on
      unperturbed living samples.

PMID- 1975612
TI  - Response of cultured human airway epithelial cells to X-rays and energetic alpha
      particles.
AB  - Radon and its progeny, which emit alpha-particles during decay, may play an
      important role in inducing human lung cancer. To gain a better understanding of
      the biological effects of alpha-particles in human lung we studied the response
      of cultured human airway epithelial cells to X-rays and monoenergetic helium
      ions. Our experimental results indicated that the radiation response of primary
      cultures was similar to that for airway epithelial cells that were transformed
      with a plasmid containing an origin-defective SV40 virus. The RBE for cell
      inactivation determined by the ratio of D0 for X-rays to that for 8 MeV helium
      ions was 1.8-2.2. The cross-section for helium ions, calculated from the D0
      value, was about 24 microm 2 for cells of the primary culture. This cross-section
      is significantly smaller than the average geometric nuclear area (approximately
      180 microms 2), suggesting that an average of 7.5 alpha-particles (8 MeV helium
      ions) per cell nucleus are needed to induce a lethal lesion.

PMID- 1975613
TI  - Hyaluronan reflects the pre-fibrotic inflammation in irradiated rat lung:
      concomitant analysis of parenchymal tissues and bronchoalveolar lavage.
AB  - The pathogenesis of pulmonary fibrosis is a complicated chain of interactions
      between cells and molecules. During recent years bronchoalveolar lavage (BAL) in
      patients with various interstitial lung disorders has increased our knowledge of
      the fibrosis process and focused on new interesting interactions. Here we present
      an animal model which makes it possible to apply both morphological and
      immunohistochemical tissue staining to perform bronchoalveolar lavage in the same
      animal. Irradiation is an established method for experimentally evoking lung
      fibrosis in animals. Rats received irradiation (30 Gy) to the lower parts of both
      lungs. Bronchoalveolar lavage was performed in the right lung. The biochemical
      determination of lavage concentration of hyaluronan (HA) and cellular
      differential counts were compared with interstitial morphology. Animals were
      sacrificed and analysed 2, 4, 6, 8 and 10 weeks after irradiation. After 6 weeks
      a massive increase in connective tissue mast cells was seen in the peribronchial
      and alveolar-interstitial tissue. This mastocytosis was closely related to a
      marked increase in HA. It became obvious that, in this model, cellular analysis
      of BAL fluid did not correctly reflect the cellular changes in the lung
      interstitium. While BAL revealed a pronounced increase of neutrophils with no--or
      only very few--mast cells, a concomitant increase in mononuclear cells and mast
      cells was seen in the lung interstitium. In contrast an increase in HA in BAL
      correlated well with an increase in HA-deposition in the lung interstitium,
      indicating that measurement of a non-cellular component, such as HA, may better
      reflect the tissue inflammation.

PMID- 1975614
TI  - Re-irradiation of mouse kidneys: a comparison of re-treatment tolerance after
      single and fractionated partial tolerance doses.
AB  - Mouse kidneys were bilaterally irradiated with fractionated doses of 15 X 1.2 Gy,
      15 X 1.6 Gy or 15 X 2.0 Gy. After an interval of 26 weeks the mice were re
      irradiated with a range of single doses and functional kidney damage was measured
      (from clearance of [51Cr]EDTA) at monthly intervals until 36 weeks after re
      irradiation. Re-irradiation tolerance was assessed from a comparison of dose
      response curves for renal damage in re-treated mice compared with age-matched
      controls, which received only the re-treatment single doses. Fractionated
      irradiation markedly reduced the tolerance to subsequent re-irradiation after 6
      months. The data indicated a continuous progression of the initial damage, even
      when the doses used were below the threshold level required to give measurable
      functional damage. These results were qualitatively similar to those previously
      published for re-irradiation of mouse kidneys after single doses. A quantitative
      comparison of the re-treatment tolerance after fractionated and single-dose
      irradiation indicated, however, that fractionated irradiation to partial
      tolerance was less damaging than predicted on the basis of the linear-quadratic
      (LQ) model. These results suggest either the failure of the LQ model for renal
      irradiation damage at low doses per fraction or, possibly, the presence of two
      subpopulations in the kidney: one population responsible for overt functional
      damage and the second population leading to subthreshold damage not normally
      expressed as functional impairment.

PMID- 1975616
TI  - Binding of the T cell activation monoclonal antibody Ta1 to dipeptidyl peptidase
      IV.
AB  - The monoclonal antibodies, Ta1 and IOT15, define T cell activation cell surface
      markers and have been assigned to the CD26 leukocyte differentiation antigen
      cluster. Dipeptidyl peptidase IV (DPP IV, EC 3.4.14.5) is an exoaminopeptidase
      that, among leukocytes, is expressed almost exclusively on activated T cells.
      Comparative binding studies showed that the Ta1 mAb binds to DPP IV purified from
      human placenta as well as in extracts of the human YT lymphoid cell line and of
      CD3 stimulated normal human peripheral blood mononuclear cells. The mAb IOT15 did
      not bind to DPP IV from any source even upon repeated incubations. Western blot
      analysis of YT cell extracts revealed that Ta1 and IOT15 bound to distinctly
      different molecular weight molecules. Immunofluorescent cell surface capping
      experiments showed that capping of the IOT15 did not alter the surface
      distribution of the Ta1 fluorescence. The capping results combined with the DPP
      IV binding results indicate that IOT15 and Ta1 mAb's bind to different,
      apparently unassociated, molecules on the surface of T cells and that only Ta1
      binds the T cell surface enzyme DPP IV.

PMID- 1975615
TI  - Beta adrenoceptors and regenerating corneal epithelium.
AB  - Beta blockers inhibit corneal re-epithelialization. This may be due to beta-2
      receptor controlled mechanisms. To investigate this possibility we performed a
      randomized, double-masked study involving 60 rabbit iatrogenic induced corneal
      ulcers produced with iodine vapour. Two beta specific drug compounds were tested,
      namely, betaxolol hydrochloride 0.25% (Alcon) (beta 1) and L132-468 (Sandoz,
      Basel) 0.25% (beta 2), and phosphate-buffered solution (PBS) as control. There
      was no statistical difference in the wound healing rates among all groups at 24
      hours but there were significant differences at 48 hours (p less than 0.01). At
      72 hours, the L132-468 treated groups showed significantly less healing than the
      betaxolol hydrochloride treated group. The PBS-treated group was healed at this
      time. By 20th post burning day, SEM revealed that betaxolol hydrochloride treated
      corneas were completely healed with normal epithelial microvilli. The L132-468
      treated corneas were also healed but desquamation and abnormal cells were
      observed. In conclusion, beta-2 blockers inhibit corneal re-epithelialization
      more potently than beta-1 blockers.

PMID- 1975617
TI  - Hormonal regulation of adult sympathetic neurons: the effects of castration on
      neuropeptide Y, norepinephrine, and tyrosine hydroxylase activity.
AB  - Previous studies utilizing the hypogastric ganglia (HG) have indicated that
      gonadal steroids exert organizational and activational effects on noradrenergic
      biochemistry. Bilateral castration of male rodents at birth prevents the normal
      maturation of tyrosine hydroxylase (T-OH) activity in the HG; castration during
      adulthood results in a progressive decline in T-OH activity. Testosterone
      replacement corrects both the ontogenetic and adult functional alterations in the
      neurotransmitter-synthesizing enzyme. The present studies in adult male rats
      extend these previous observations and asked the question whether gonadal
      steroids regulate the neurotransmitters neuropeptide Y (NPY) and norepinephrine
      (NE) in the HG. Adult rodents were castrated and ganglia T-OH, NPY, and NE were
      examined at various time points after surgery. All three indices of sympathetic
      neuron biochemistry declined following castration, but they exhibited different
      profiles. It appears that hormones may affect enzyme activity and
      neurotransmitter pools differently within neurons. Testosterone replacement
      therapy fully restored T-OH activity, and NPY and NE levels in the HG. These
      studies extend the activational role of testosterone in regulating sympathetic
      neuron neurotransmitter and neuropeptide levels as well as neurotransmitter
      synthesizing enzymes.

PMID- 1975618
TI  - Receptor scintigraphy with a radioiodinated somatostatin analogue: radiolabeling,
      purification, biologic activity, and in vivo application in animals.
AB  - Radioiodinated Tyr-3-octreotide, a somatostatin analogue, is a useful ligand for
      the in vitro detection of somatostatin receptors. In this study, we have
      investigated the possible in vivo application of this radioligand in the
      detection of somatostatin receptor-bearing tumors by scintigraphy. The specific
      somatostatin-like biologic activity of radioiodinated Tyr-3-octreotide was
      confirmed in vitro: (a) radioiodinated Tyr-3-octreotide competes in the nanomolar
      range with specific receptor binding of somatostatin to suspended human
      meningioma membranes and (b) the secretion of growth hormone by cultured rat
      pituitary cells was similarly inhibited by iodinated Tyr-3-octreotide and
      somatostatin. In rats, intravenously injected 123I-Tyr-3-octreotide is rapidly
      cleared from the circulation mainly by the liver. Although this rapid clearance
      limits the amount of tracer available for somatostatin receptor-bearing tumors,
      the advantage of this rapid clearance is that the background level is rapidly
      reduced in favor of scintigraphic imaging of these tumors. Pancreatic tumors in
      rats were localized by scintigraphy after intravenous injection of 123I-Tyr-3
      octreotide.

PMID- 1975619
TI  - Epithelial transport of drugs in cell culture. I: A model for studying the
      passive diffusion of drugs over intestinal absorptive (Caco-2) cells.
AB  - A human intestinal cell line, Caco-2, was used as a model to study the passive
      diffusion of drugs across intestinal epithelium. The cells formed continuous
      monolayers when grown on permeable filters of polycarbonate. After 10 days in
      culture, the monolayers had a transmembrane resistance of approximately 260
      ohms.cm2 and a cell density of 0.9 x 10(6) cells/cm2. At this time the cells were
      impermeable to [14C]polyethyleneglycol (MW 4000). These characteristics remained
      constant for 20 days (i.e., from day 10 to day 30). Six beta-blocking agents with
      a 2000-fold range of lipophilicity were studied for their transepithelial
      transport properties. The transport parameters were independent of drug
      concentration and transport direction. The apparent permeability coefficients
      ranged from 41.91 +/- 4.31 x 10(-6) cm/s for the most lipophilic drug,
      propranolol, to 0.203 +/- 0.004 x 10(-6) cm/s for the most hydrophilic drug,
      atenolol. The transport parameters were compared with those published for rat
      ileum. The transport rates were similar for four out of five drugs. Atenolol was
      transported at a slower rate in the Caco-2 model, which may be explained by the
      fact that the Caco-2 cells form a tighter epithelium than the rat ileal
      enterocytes. The findings of this paper indicate that Caco-2 cells may be used to
      model the intestinal absorption of drugs.

PMID- 1975620
TI  - Identification of fenoldopam prodrugs with prolonged renal vasodilator activity.
AB  - Fenoldopam (SK&F 82526) is a short-acting selective dopamine-1 agonist in
      clinical trials for the treatment of hypertension, congestive heart failure and
      renal failure. In the present study, we tested various N-ethyl carbamate esters
      of fenoldopam in the conscious dog instrumented with a femoral arterial Vascular
      Access-Port and a renal artery flow probe. Oral administration of SK&F R-82526 at
      1 and 3 mumol/kg resulted in transient (30-60 min) dose-dependent increases in
      plasma fenoldopam levels and renal blood flow. Administration of the 7,8-bis-N
      ethyl carbamate ester of R-fenoldopam (SK&F R-106114) and the 4',7,8-tris-N-ethyl
      carbamate ester of R-fenoldopam (SK&F R-105058) at 1, 3 and 10 mumol/kg p.o. also
      resulted in dose-dependent increases in plasma fenoldopam levels and renal blood
      flow; however, both parameters remained elevated for at least 4 hr. Intravenous
      administration of SK&F R-105058 also resulted in sustained plasma fenoldopam
      levels and increases in renal blood flow, indicating that slow absorption was not
      the cause of the sustained effect. The present study indicates that N-ethyl
      carbamate esters of fenoldopam are fenoldopam prodrugs which result in sustained
      increases in renal blood flow and plasma fenoldopam levels.

PMID- 1975621
TI  - Regulatory role of enteric mu and kappa opioid receptors in the release of
      acetylcholine and norepinephrine from guinea pig ileum.
AB  - We examined the role of opioid receptor subtypes in the contraction and release
      of acetylcholine (ACh) and norepinephrine in longitudinal muscle-myenteric plexus
      preparations of the guinea pig ileum. [D-Ala2, N-Me-Phe4, Gly5-ol]enkephalin
      (DAMGO) (10(-8) to 10(-5) M) inhibited the contraction and the release of ACh
      evoked by 0.2 and 1 Hz of electrical stimulation (ES), whereas the response to 5
      Hz was enhanced by low concentrations of DAMGO (10(-9) to 10(-8) M) and inhibited
      by high concentrations (10(-7) to 10(-5) M); naloxone antagonized these effects.
      In preparations treated with yohimbine, DAMGO inhibited the ES (5 Hz)-evoked
      contraction and ACh release, but failed to enhance either effect. Dynorphin-A
      inhibited the contraction and ACh release evoked by 0.2, 1 and 5 Hz of ES, and
      the effect of dynorphin-A was mimicked by U-69593 [5 alpha,7 alpha,8 beta-(-)-N
      methyl-N-[7- (pyrrolinyl)-1-ozaspiro(4,5)dec-8-yl]-benzene] and antagonized by MR
      2266 [(-)-alpha-5,9-diethyl-2-(3-furylmethyl)-2'-hydroxy-6,7-benzomorphan]. The
      release of norepinephrine evoked by 5 Hz of ES was inhibited by DAMGO (10(-10) to
      10(-6) M), but not by U-69593, and the effect of DAMGO was antagonized by
      naloxone. Thus, it would appear that mu-opioid receptors are present on both
      cholinergic and adrenergic neurons, whereas kappa-opioid receptors are present on
      cholinergic neurons. The affinity of DAMGO was 30 times higher for the mu-opioid
      receptors on the adrenergic than on the cholinergic neurons.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1975622
TI  - Effect of Phe-D-Met-Arg-Phe-NH2 and other Phe-Met-Arg-Phe-NH2-related peptides on
      mouse colonic propulsive motility: a structure-activity relationship study.
AB  - The effect of several i.c.v.-administered FMRFamide (Phe-Met-Arg-Phe-NH2)-like
      peptides (FaRPs) on mouse colonic propulsive motility was examined. Dose-related
      inhibition of propulsive motility (measured as an increase in the time of colonic
      bead expulsion) was produced by analogs with either the sequence (-)F[X]RFamide
      or with the FMRFamide sequence containing D-amino acid substitutions. The C
      terminal dipeptide sequence Arg-Phe-NH2 was sufficient to produce this effect. D
      amino acid substitution in the second position, i.e., [D-Met2]-FMRFamide (DMFa),
      conferred significantly enhanced activity (nearly maximal obtainable response
      under the test conditions) in this preparation (ED25 = 2.3 micrograms = 3.8
      nmol). DMFa did not block the action of morphine but, like morphine, was blocked
      by the opioid antagonist naloxone and was attenuated by 24-hr pretreatment with
      the selective mu-1 opioid antagonist naloxonazine (35 mg/kg s.c.). It is
      concluded that a variety of FaRPs, particularly those with a nonpolar residue in
      the first position and with Arg in the third position, behave as opioid-like
      agonists, not antagonists, on mouse colonic propulsive motility. DMFa is
      identified as the most active FaRP studied to date on this endpoint.

PMID- 1975623
TI  - Possible involvement of membrane-stabilizing action in beneficial effect of beta
      adrenoceptor blocking agents on hypoxic and posthypoxic myocardium.
AB  - The present study was designed to elucidate a possible involvement of membrane
      stabilizing action of beta blocking agents in posthypoxic recovery of cardiac
      contractile function and myocardial metabolism. Propranolol and acebutolol, which
      possess a membrane-stabilizing action, and atenolol and metoprolol, which lack
      this action, were used in the isolated, perfused rabbit heart. The membrane
      stabilizing effects of these agents were assessed on the basis of the effects on
      the maximal driving frequency of the left atria. Reoxygenation of hearts for 45
      min following 20-min hypoxia resulted in little recovery of cardiac contractile
      force, sustained rise in resting tension, insufficient recovery of myocardial
      high-energy phosphates, accumulation of the tissue calcium and sodium and marked
      release of creatine kinase and ATP metabolites from the hearts. Treatment of
      hypoxic hearts with either 100 microM propranolol, 200 microM acebutolol, 200
      microM atenolol or 100 microM metoprolol was commenced when the contractile force
      declined to 30% of the initial level and terminated at 20-min hypoxia. Treatment
      with either propranolol or acebutolol produced a significant posthypoxic recovery
      of cardiac contractile force, resting tension and myocardial high-energy
      phosphates, and a profound suppression of the tissue calcium and sodium
      accumulation and the loss of ATP metabolites from perfused hearts. In contrast,
      neither atenolol nor metoprolol affected these changes induced by the hypoxic
      insult and the following reoxygenation. The results suggest that membrane
      stabilizing action of beta blocking agents plays an important role in the
      protection against posthypoxic cardiac contractile dysfunction and metabolic
      disturbances.

PMID- 1975624
TI  - Involvement of alpha-2 adrenergic receptor subtypes in hyperglycemia.
AB  - Alpha-2 adrenoceptor stimulation induces in the mouse a hyperglycemic response
      which is accompanied by a concomitant inhibition of insulin secretion. To test
      the possibility that one of the postulated subtypes of alpha-2 adrenoceptors is
      preferentially implicated in this response, we compared the interaction of
      several drugs with known selectivity toward alpha-2A or alpha-2B adrenoceptor
      subtypes in our model. The alpha-2A preferential agonist oxymetazoline induced in
      the mouse a hyperglycemic response similar to that of the nonselective alpha-2
      adrenoceptor agonist UK 14.304. This hyperglycemic response to oxymetazoline was
      accompanied by a concomitant inhibition of insulin release. Both the effect on
      glycemic level and the inhibition of insulin release by oxymetazoline were
      antagonized by the alpha-2 adrenoceptor antagonist idazoxan. The alpha-2B
      preferential antagonists ARC-239, prazosin or chlorpromazine failed to block the
      modifications in both glycemic and insulin levels induced by alpha-2 adrenoceptor
      stimulation. The nonselective antagonists rauwolscine, yohimbine, WY 26703,
      phentolamine and corynanthine, as well as the receptor antagonists with alpha-2A
      selectivity like WB 4101, idazoxan and tolazoline, dose-dependently antagonized
      both the glycemic and the insulin responses to UK 14.304. A positive correlation
      was obtained between the potencies of these drugs in antagonizing the
      hyperglycemic response to UK 14.304 and their affinities for alpha-2A adrenergic
      receptors (r = 0.918, P less than .001) but no correlation was obtained with
      their affinities for alpha-2B adrenergic receptors (r = 0.048, P = N.S.)(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1975625
TI  - Pharmacological characterization of alpha-2 adrenergic receptor subtype involved
      in the release of insulin from isolated rat pancreatic islets.
AB  - Alpha-2 adrenoceptors are involved in the inhibition of insulin release induced
      by sympathetic nerve stimulation. To test the possibility that one of the
      postulated subtypes of alpha-2 adrenoceptors is differentially implicated in the
      inhibition of insulin release, we compared the effects of several agonists and
      antagonists with preferential selectivity for the alpha-2 adrenoceptor subtypes
      on the release of insulin induced by glucose in rat isolated islets. Similar to
      the inhibition of glucose-evoked release of insulin by the alpha-2 agonist
      (nonsubtype selective) UK 14.304, the alpha-2A preferential agonist
      oxymetazoline, concentration-dependently inhibited the release of insulin.
      Glucose-evoked insulin release was similarly inhibited by other alpha-2
      adrenoceptor agonists such as clonidine, p-aminoclonidine, epinephrine and
      norepinephrine. However, neither the alpha-1 selective agonist cirazoline, nor
      the beta adrenoceptor agonist isoproterenol affected glucose-evoked insulin
      release, thus suggesting that this inhibitory effect is mediated by alpha-2
      adrenoceptors, possibly of the alpha-2A subtype. The inhibition of glucose-evoked
      insulin release induced by the alpha-2 adrenoceptor agonists was concentration
      dependently inhibited by the alpha-2 antagonists yohimbine, phentolamine,
      rauwolscine and idazoxan. However, neither the alpha-1 selective antagonist
      prazosin, nor the beta selective antagonist propranolol attenuated the inhibition
      of insulin release induced by alpha-2 adrenoceptor agonists. Furthermore, the
      inhibition of insulin release induced by UK 14.304 was concentration-dependently
      antagonized by the alpha-2A preferential antagonist WB-4101.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1975626
TI  - Alpha-2 adrenoceptor in rat jejunum epithelial cells: characterization with
      [3H]RX821002 and distribution along the villus-crypt axis.
AB  - Alpha-2 adrenergic receptivity of rat jejunum epithelial cells was studied using
      the new antagonist radioligand, [3H]RX821002 [( 3H]-2-(2-methoxy-1,4-benzodioxan
      2-yl)-2-imidazoline). All the parameters of [3H]RX821002 binding were consistent
      with the labeling of an alpha-2 adrenoceptor. The use of this probe was moreover
      extremely convenient, because contrarily to [3H]yohimbine and [3H]rauwolscine,
      [3H]RX821002 displayed in this tissue a very high affinity (Kd = 0.54 +/- 0.12
      nM) and a low level of nonspecific binding (5% at 1 nM [3H]RX821002). Competition
      studies with various antagonists and agonists showed that the labeled sites were
      alpha-2-selective and stereospecific. Oxymetazoline was much more potent than
      chlorpromazine or prazosin suggesting that the receptor is of the alpha-2
      subtype. Yohimbine and rauwolscine were equipotent, which is also in agreement
      with the pharmacological definition of this subtype. These two compounds
      displayed, however, a rather weak affinity (Ki approximately 40 nM), which is
      somewhat different with what one should expect for a true alpha-2A adrenoceptor.
      Altogether the competition data indicated that the alpha-2 adrenoceptor from rat
      jejunal epithelium is neither an alpha-2A, nor an alpha-2B, nor an alpha-2c
      adrenoceptor and may belong to a fourth subtype.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1975627
TI  - Agonist interaction with alkylation-sensitive and -resistant alpha-1 adrenoceptor
      subtypes.
AB  - The interaction of agonists with alpha-1 receptor subtypes sensitive and
      resistant to alkylation by a prazosin analog [1-(4-amino-6,7-dimethoxy-2
      quinazolinyl)-4-(2-bicyclo[2.2.2]octa-2,5- diene-z-carbonyl)-piperazine; SZL-49]
      has been examined. In rat aortic rings, SZL-49 (0.1-10 nM) shifted the dose
      response curves for norepinephrine and phenylephrine to the right. The curves
      were biphasic, consisting of high and low affinity components. At greater than 10
      nM, the curves became monophasic. After SZL-49 treatment, the response to
      norepinephrine was partially antagonized by diltiazem. Chlorethylclonidine (1-100
      microM) also produced biphasic dose-response curves. Phenylephrine bound to high
      and low affinity sites labeled by [3H]prazosin, and the high affinity site was
      eliminated by SZL-49. SZL-49 (i.p.) shifted the pressor dose-response curve for
      phenylephrine to the right but did not decrease the maximal response.
      Chlorethylclonidine was much less potent than SZL-49 at shifting the pressor dose
      response curve. Pertussis toxin, 50 micrograms/kg i.v., shifted the phenylephrine
      pressor dose-response curve in control and SZL-49-treated animals. SZL-49
      inhibited norepinephrine-induced inositol phosphate formation, whereas
      chlorethylclonidine had no effect on inositol phosphate formation. These data
      show: 1) both in vitro and in vivo, alpha-1 receptor subtypes sensitive and
      resistant to alkylation by SZL-49 can mediate the full response of agonists; 2)
      these subtypes exhibit high and low affinity for agonists; 3) responses mediated
      by either subtype are partially dependent on calcium channel activity and a
      pertussis toxin-sensitive G-protein; 4) the SZL-49 sensitive site is able to
      enhance the formation of inositol phosphates.

PMID- 1975628
TI  - Neuroleptics and psychic indifference.

PMID- 1975629
TI  - Recombination or heterogeneity: is there a second locus for adult polycystic
      kidney disease?
AB  - Twenty-four families with adult onset polycystic kidney disease were typed for
      markers flanking the PKD1 locus on chromosome 16. The aggregated results gave a
      significant lod score in favour of linkage to PKD1. Within this group of families
      two showed unusual features: recombinations, including double recombinations,
      and, in one family, an unexpectedly high proportion of affected people. We
      consider the evidence that in these families the disease might result from a
      mutation at a different locus, PKD2, not linked to PKD1. We suggest that a useful
      test is to compare the relative numbers of meioses apparently non-recombinant and
      doubly recombinant for markers flanking the normal disease locus, ignoring
      meioses recombinant for only a single marker. Using this test, neither our two
      families nor the data published so far on other families provide compelling
      evidence for the existence of a second locus for adult polycystic kidney disease.
      For genetic counselling in families too small to give internal evidence for or
      against linkage, the extra uncertainty can be handled by using a higher
      recombination rate.

PMID- 1975630
TI  - [Autografts with peripheral blood stem cells].
AB  - This paper reports a clinical and laboratory experience of peripheral blood stem
      cell (PBSC) autografts at a single institute. Twenty-eight children with various
      types of cancer underwent a total of 90 leukaphereses to collect PBSC and 17 of
      them subsequently received marrow-ablative therapy and PBSC autografts. We found
      that frozen-thawed progenitor dose is important in determining the rate of
      hematopoietic recovery after transplantation; in 11 patients who received more
      than 1 x 10(5) CFU-GM/kg, the granulocyte count reached to 0.5 x 10(9)/L in two
      weeks. With conditioning chemotherapy without total body irradiation, 6 of 14
      patients with high-risk acute leukemia or non-Hodgkin's lymphoma have survived
      disease-free 3 to 25 months posttransplant. This approach may have a potential to
      induce prolonged remission-interval and ultimate cure.

PMID- 1975631
TI  - [Genetic control of cardiac function and the new prospects of clinical
      cardiology].

PMID- 1975632
TI  - Nigrostriatal dopamine neurons, D1 transmission in basal and ischemic states and
      protective effects of gangliosides.

PMID- 1975633
TI  - Immunohistochemical localization of lysyl oxidase with monoclonal antibodies.
AB  - Lysyl oxidase initiates the cross-linking of collagen and elastin by catalyzing
      the formation of the lysine-derived aldehyde. We cloned three hybridoma cell
      lines which secrete monoclonal antibodies to human lysyl oxidase. The
      localization of lysyl oxidase was investigated in various tissues and in cultured
      cells using an immunofluorescent antibody method. Antibodies showed a strong
      immunostaining in the aorta and dermal connective tissue suggesting a close
      relation to elastin and collagen. Fibroblasts, chondrocytes, and smooth muscle
      cells also yielded a marked positive immunoreaction as did a variety of
      nonfibroblastic cells such as endothelial cells, basal cells, biliary epithelial
      cells, and glomerular epithelial cells. In cultured cells, including human
      fibroblasts, an intense immunoreaction manifested as fine, filamentous structures
      in the cytoplasm. It is suggested that lysyl oxidase is associated with
      cytoskeletal protein.

PMID- 1975634
TI  - Metabolism of doxylamine succinate in Fischer 344 rats. Part III: Conjugated
      urinary and fecal metabolites.
AB  - Elimination and metabolic profiles of the glucuronide products of doxylamine and
      its N-demethylated metabolites were determined after the oral administration of
      (14C)-doxylamine succinate (13.3 and 133 mg/kg doses) to male and female Fischer
      344 rats. The cumulative urinary and fecal eliminations of these conjugated
      doxylamine metabolites at the 13.3 mg/kg dose were 44.4 +/- 4.2% and 47.3 +/-
      8.1% of the total recovered dose for male and female rats, respectively. The
      cumulative urinary and fecal eliminations of conjugated doxylamine metabolites at
      the 133 mg/kg dose were 55.2 +/- 2.6% and 47.9 +/- 2.5% of the total recovered
      dose for male and female rats, respectively. The conjugated doxylamine
      metabolites that were isolated, quantitated, and identified are doxylamine O
      glucuronide, N-desmethyl-doxylamine O-glucuronide, and N,N-didesmethyldoxylamine
      O-glucuronide.

PMID- 1975635
TI  - The detection of residual acute lymphoblastic leukemia cells with immunologic
      methods and polymerase chain reaction: a comparative study.
AB  - In this study we applied double color immunofluorescence analysis and polymerase
      chain reaction (PCR) amplification of rearranged TCR delta genes for detecting
      residual leukemia in the posttreatment bone marrow (BM) samples taken from four
      patients in morphological remission. In three of these patients (nos. 1-3; T-ALL)
      a combination of CD3 and anti-TdT antibodies (Abs) was used to identify residual
      blasts while in patient 4 (B lineage ALL) the combination CD13/TdT served to
      detect residual disease. Two rounds of PCR primed by nested amplimers were
      carried out to prepare clonospecific probes from presentation DNA and to
      investigate the follow-up samples. In patients 1 and 2 no cCD3+/TdT+ cells were
      seen posttreatment, but PCR amplification of the TCR V delta 1-D-J delta 1 region
      revealed residual disease in both patients. Patient 1 underwent allogeneic BM
      transplant (BMT) 8 months after diagnosis and is well 3 months post-BMT while
      patient 2 relapsed 12 months after presentation. In patient 3 the remission
      samples investigated 2 and 3 months after diagnosis did not contain cCD3+/TdT+
      cells, but in the sample collected at 4 months a few such cells (0.0001-0.001%)
      could be detected. In the same sample, PCR amplification of the TCR V delta 2-D-J
      delta 1 region indicated the presence of 10(-4)-10(-3) residual leukemic cells.
      These findings predicted full morphological relapse which occurred 2 months
      later. In patient 4 CD13/TdT double positive cells were clearly seen 2 and 3
      months after presentation. PCR amplification of the V delta 2-D delta 3
      recombination also revealed residual blasts when applied to one of such
      "remission" samples. After further remission induction treatment, no immunologic
      evidence of residual disease was detected. This patient received an allogeneic
      BMT 8 months after diagnosis and is disease free 4 months after BMT. Our data
      indicate that both double color immunofluorescence and PCR analysis offer
      powerful tools to study residual leukemia and highlight the advantages as well as
      the potential limitations of each technique.

PMID- 1975636
TI  - D-2 dopamine autoreceptor selective drugs: do they really exist?
AB  - The catecholamine dopamine plays an important role as a neurotransmitter or
      neurohormone in the brain and pituitary gland. Dopamine exerts its effects
      through activation of two types of receptors called D-1 and D-2. These receptors
      are distinguished by their different pharmacological characteristics and signal
      transduction mechanism(s). Release of dopamine inhibits the activity of
      dopaminergic neurons through activation of so-called dopamine autoreceptors which
      are of the D-2 type. In general, these receptors occur both in the soma-dendritic
      region of the dopaminergic neuron, where they are involved in the inhibition of
      the firing rate and on the dopaminergic terminals where they mediate the
      inhibition of dopamine synthesis and release. D-2 receptors occur also on the
      target cells of dopaminergic neurons both in the brain (postsynaptic D-2
      receptors) and pituitary gland. On the basis of data gathered from in vivo
      (behavioral- as well as electrophysiological) studies it has been concluded that
      D-2 agonists are much more potent at dopamine autoreceptors as compared to
      postsynaptic D-2 receptors, indicating the possibility of a pharmacological
      distinction between these differentially located D-2 receptors. This concept led
      to the introduction of a whole group of drugs allegedly displaying a selective
      agonist profile at the dopamine autoreceptor. In contrast, biochemical (in vitro)
      studies with brain tissue as well as the pituitary gland, did not reveal any
      significant difference between the pharmacological profiles of autoreceptors and
      postsynaptic D-2 receptors. In the present minireview a balanced discussion is
      presented of these in vivo and in vitro findings and it is concluded that both
      autoreceptors as well as postsynaptic D-2 receptors are similar if not identical
      entities.

PMID- 1975637
TI  - A controlled study of early neurologic abnormalities in men with asymptomatic
      human immunodeficiency virus infection.
AB  - BACKGROUND: Although neurologic complications are frequent in the acquired
      immunodeficiency syndrome, their incidence and progression in early human
      immunodeficiency virus (HIV) infection remain controversial. The goal of this
      study was to assess neurologic manifestations in asymptomatic carriers of HIV.
      METHODS: We studied 29 HIV-seropositive homosexual men and 33 seronegative
      homosexual controls by means of neurologic and neuropsychological examinations,
      magnetic resonance imaging (MRI), and electrophysiologic tests
      (electroencephalography, multimodal evoked-potential tests, and otoneurologic
      tests). After six to nine months, the tests were repeated in 27 seropositive men
      and 30 controls. The investigators were blind to the serologic status of the
      subjects. RESULTS: The seropositive subjects had a mean CD4+ lymphocyte count of
      635 X 10(6) per liter. Neurologic and neuropsychological examination, MRI, and
      measurements of pattern visual evoked potentials did not show significant
      differences between the two groups. The latencies of the median-nerve
      somatosensory evoked potentials were slightly prolonged in the seropositive men.
      The initial electroencephalogram was judged abnormal in 8 of 27 of the
      seropositive subjects (30 percent) as compared with none of the controls, with a
      slowing of fundamental activity, anterior spread [corrected] of alpha rhythm,
      subnormal reactivity, and unusual anterior theta activities. These findings were
      confirmed by computerized spectral analysis. The second electroencephalogram was
      abnormal in 10 of 25 of the seropositive men (40 percent). The otoneurologic
      evaluation identified abnormalities in the central auditory or vestibulo-ocular
      pathways in 34 percent of the seropositive men (10 of 29), as compared with 6
      percent of the controls (2 of 33), on the first examination and in 44 percent (12
      of 27) and 7 percent (2 of 30), respectively, on the second examination.
      Altogether, electrophysiologic abnormalities were found in 67 percent of the
      seropositive men (18 of 27) and 10 percent of the controls (3 of 30) (P less than
      0.00005). CONCLUSIONS: In persons with asymptomatic HIV infection,
      electrophysiologic tests may be the most sensitive indicators of subclinical
      neurologic impairment. Electrophysiologic abnormalities are far more common in
      asymptomatic carriers of HIV than in controls and tend to progress over time.

PMID- 1975638
TI  - Dealing with data.

PMID- 1975639
TI  - Different voltage-dependent thresholds for inducing long-term depression and long
      term potentiation in slices of rat visual cortex.
AB  - In the hippocampus and neocortex, high-frequency (tetanic) stimulation of an
      afferent pathway leads to long-term potentiation (LTP) of synaptic transmission.
      In the hippocampus it has recently been shown that long-term depression (LTD) of
      excitatory transmission can also be induced by certain combinations of synaptic
      activation. In most hippocampal and all neocortical pathways studied so far, the
      induction of LTP requires the activation of N-methyl-D-aspartate (NMDA) receptor
      gated conductances. Here we report that LTD can occur in neurons of slices of the
      rat visual cortex and that the same tetanic stimulation can induce either LTP or
      LTD depending on the level of depolarization of the postsynaptic neuron. By
      applying intracellular current injections or pharmacological disinhibition to
      modify the depolarizing response of the postsynaptic neuron to tetanic
      stimulation, we show that the mechanisms of induction of LTD and LTP are both
      postsynaptic. LTD is obtained if postsynaptic depolarization exceeds a critical
      level but remains below a threshold related to NMDA receptor-gated conductances,
      whereas LTP is induced if this second threshold is reached.

PMID- 1975640
TI  - Human dopamine D1 receptor encoded by an intronless gene on chromosome 5.
AB  - Receptors for dopamine have been classified into two functional types, D1 and D2.
      They belong to the family of receptors acting through G (or guanine nucleotide
      binding) proteins. D2 receptors inhibit adenylyl cyclase, but D1 receptors
      stimulate adenylyl cyclase and activate cyclic AMP-dependent protein kinases.
      Dopamine D1 and D2 receptors are targets of drug therapy in many psychomotor
      disorders, including Parkinson's disease and schizophrenia, and may also have a
      role in drug addiction and alcoholism. D1 receptors regulate neuron growth and
      differentiation, influence behaviour and modify dopamine D2 receptor-mediated
      events. We report here the cloning of the D1 receptor gene, which resides on an
      intronless region on the long arm of chromosome 5, near two other members of the
      G-linked receptor family. The expressed protein, encoded by 446 amino acids,
      binds drugs with affinities identical to the native human D1 receptor. The
      presence of a D1 receptor gene restriction fragment length polymorphism will be
      helpful for future disease linkage studies.

PMID- 1975641
TI  - Inhibition of HIV replication by pokeweed antiviral protein targeted to CD4+
      cells by monoclonal antibodies.
AB  - Functional impairment and selective depletion of CD4+ T cells, the hallmark of
      AIDS, are at least partly caused by human immunodeficiency virus (HIV-1) type 1
      binding to the CD4 molecule and infecting CD4+ cells. It may, therefore, be of
      therapeutic value to target an antiviral agent to CD4+ cells to prevent infection
      and to inhibit HIV-1 production in patients' CD4+ cells which contain proviral
      DNA. We report here that HIV-1 replication in normal primary CD4+ T cells can be
      inhibited by pokeweed antiviral protein, a plant protein of relative molecular
      mass 30,000, which inhibits replication of certain plant RNA viruses, and of
      herpes simplex virus, poliovirus and influenza virus. Targeting pokeweed
      antiviral protein to CD4+ T cells by conjugating it to monoclonal antibodies
      reactive with CD5, CD7 or CD4 expressed on CD4+ cells, increased its anti-HIV
      potency up to 1,000-fold. HIV-1 replication is inhibited at picomolar
      concentrations of conjugates of pokeweed antiviral protein and monoclonal
      antibodies, which do not inhibit proliferation of normal CD4+ T cells or CD4
      dependent responses. These conjugates inhibit HIV-1 protein synthesis and also
      strongly inhibit HIV-1 production in activated CD4+ T cells from infected
      patients.

PMID- 1975642
TI  - Pharmacology. The dopamine connection.

PMID- 1975643
TI  - Neurotransmitter identity doubt.

PMID- 1975644
TI  - Molecular cloning and characterization of a novel dopamine receptor (D3) as a
      target for neuroleptics.
AB  - A dopamine receptor has been characterized which differs in its pharmacology and
      signalling system from the D1 or D2 receptor and represents both an autoreceptor
      and a postsynaptic receptor. The D3 receptor is localized to limbic areas of the
      brain, which are associated with cognitive, emotional and endocrine functions. It
      seems to mediate some of the effects of antipsychotic drugs and drugs used
      against Parkinson's disease, that were previously thought to interact only with
      D2 receptors.

PMID- 1975645
TI  - Arachidonic acid released from striatal neurons by joint stimulation of
      ionotropic and metabotropic quisqualate receptors.
AB  - Associative stimulation of N-methyl-D-aspartate (NMDA) receptors and quisqualate
      ionotropic receptors (Qi) induces long-term potentiation at particular
      glutamatergic synapses. Release of arachidonic acid as a result of stimulation of
      NMDA receptors has been proposed to play a part in the establishment of long-term
      potentiation. But long-term plasticity events at some other glutamatergic
      synapses do not involve activation of NMDA receptors. Here we report that in
      mature striatal neurons in primary cultures, quisqualate can release arachidonic
      acid by associatively activating both quisqualate metabotropic receptors coupled
      to phospholipase C (Qp) and Qi receptors. Independent activation of these two
      receptor types with specific agonists did not stimulate arachidonic acid release.
      These results support a role for the associative activation of Qp and Qi
      receptors in synaptic plasticity events, including long-term potentiation at
      particular synapses.

PMID- 1975646
TI  - What is a physician assistant?

PMID- 1975647
TI  - Two responses to Dr. Nemeroff's article.

PMID- 1975649
TI  - Sulphasalazine in the treatment of rheumatoid arthritis: a renewed challenge.

PMID- 1975648
TI  - [When and how should primary prevention against Pneumocystis carinii pneumonia be
      carried out in HIV infection?].

PMID- 1975650
TI  - Oesophageal varices: prophylactic treatment?
AB  - Oesophageal varices: prophylactic treatment? Patients with oesophageal varices as
      a result of liver cirrhosis are at risk of bleeding from these varices. Because
      of the high mortality, specially from the first variceal haemorrhage, it would
      seem justified to pose the question: does prophylactic treatment of oesophageal
      varices reduce the risk of bleeding and improve life expectancy? A review of the
      literature shows that until now no mode of prophylactic therapy has succeeded in
      accomplishing these goals. It is not, therefore, possible at this time to advise
      the use of prophylactic treatment of oesophageal varices as a routine therapy.

PMID- 1975651
TI  - The effect of fenoldopam on renal haemodynamics and natriuresis in chronic renal
      failure.
AB  - The effect of oral administration of fenoldopam, a dopamine-1 receptor agonist,
      on blood pressure, renal haemodynamics and natriuresis was studied in 12 patients
      with chronic renal insufficiency. In addition, the effect of administering a low
      intravenous dose of fenoldopam on top of the oral dose was compared with the
      effect of the same intravenous dose given immediately before oral fenoldopam.
      Oral administration of fenoldopam (50 mg t.i.d. for 3 +/- 1 days followed by 100
      mg t.i.d. for 8 +/- 1 days) induced a significant fall in blood pressure (median
      MAP from 107 to 101 mm Hg). Compared to baseline values, body weight, effective
      renal plasma flow (ERPF), glomerular filtration rate (GFR) and fractional sodium
      excretion remained unchanged. Infusion of fenoldopam (0.05-0.1 micrograms/kg/min)
      on day 1 led to a significant fall in blood pressure (median mean arterial
      pressure from 107.0 to 98.5 mm Hg), and a significant rise in effective renal
      plasma flow (median ERPF from 132 to 146 ml/min/1.73 m2). Median fractional
      sodium excretion increased significantly from 2.1 to 3.3%. GFR, filtration
      fraction and plasma aldosterone concentration did not change. No relationship was
      found between the fenoldopam-induced changes in ERPF and natriuresis, nor between
      baseline GFR or ERPF and fenoldopam-induced urinary sodium loss. Infusion of
      fenoldopam while patients were on oral fenoldopam had no effect on blood
      pressure, ERPF or GFR. However, again natriuresis was induced, which did not
      differ significantly from the fenoldopam-induced natriuresis on day 1. We
      conclude that oral fenoldopam has a moderate blood pressure lowering effect in
      patients with chronic renal insufficiency, but exerts no effect on ERPF or GFR.
      Secondly, a fenoldopam-induced natriuresis does not appear to be related to
      changes in ERPF or aldosterone secretion.

PMID- 1975652
TI  - Amino acid neurotransmitter alterations in three sublines of Rb mice differing by
      their susceptibility to audiogenic seizures.
AB  - The levels of inhibitory amino acids (Tau, Gly), or excitatory amino acids (Glu,
      Asp) and Gln, precursor of GABA, have been determined, under resting conditions,
      in 17 brain areas of 3 sublines of inbred Rb mice displaying different responses
      to an acoustic stimulus. Rb1 mice were clonictonic seizure-prone, Rb2 mice were
      clonic seizure-prone and Rb3 mice were seizure resistant. Profile of distribution
      in the brain of each one of these amino acids differed. Maximum to minimum level
      ratio was higher for Tau (3.8) than for Glu or Asp or Gln (2). The level of Gly
      was similar in 13 out of the 17 areas examined. Multiple inter-subline
      differences were recorded for each amino acid. These differences have been
      analyzed considering the seizure susceptibility or severity of the three Rb
      sublines. Common lower levels (approximately -20%: Rb1/Rb3, Rb2/Rb3) of Gln in
      Temporal Cortex may be implicated in seizure susceptibility. Seizure severity
      (Rb1/Rb2) seems to correlate, in some areas, with additional lower amounts of
      GABA already reported and, to a lower extent, of Asp (-19% in striatum, inferior
      colliculus and cerebellum), of Tau and Gly; a tendency for a rise in Gln content
      was observed in certain others (10-20% in olfactory bulb, thalamus, hypothalamus,
      substantia nigra, and frontal, temporal and occipital cortex). The data and
      correlations recorded provide guidelines for further investigations for
      synaptosomal and metabolic alterations in the three sublines of the same strain
      of Rb mice.

PMID- 1975653
TI  - Inhibition of mitochondrial respiration by 1,2,3,4-tetrahydroisoquinoline-like
      endogenous alkaloids in mouse brain.
AB  - Since the discovery of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
      induced parkinsonism, it has been postulated that (a) MPTP-like toxin(s) such as
      1,2,3,4-tetrahydroisoquinoline (TIQ) may induce Parkinson's disease. As the
      neuronal degeneration in MPTP-induced parkinsonism is thought to be caused by the
      inhibition of the mitochondrial respiration by 1-methyl-4-phenylpyridinium ion
      (MPP+), we studied the effects of TIQ-like alkaloids including dopamine-derived
      ones on the mitochondrial respiration using mouse brains. TIQ,
      tetrahydropapaveroline (THP), and tetrahydropapaverine (THPV) produced
      significant inhibition of the state 3 and 4 respiration and respiratory control
      ratio supported by glutamate + malate, the activity of Complex I and the ATP
      synthesis. Among those compounds, THPV was most potent. Toxic properties of these
      compounds on mitochondria were quite similar to that of MPP+. Our results support
      the hypothesis that (a) MPTP- or MPP(+)-like substance(s) may be responsible for
      the nigral degeneration in Parkinson's disease.

PMID- 1975656
TI  - Effect of prolactin replacement on the number of tyrosine hydroxylase expressing
      neurons in the arcuate nuclei of Ames dwarf and normal mice.
AB  - Ames dwarf mice do not synthesize or release growth hormone or prolactin (PRL)
      and have very poorly developed tuberoinfundibular dopaminergic (TIDA) neurons. An
      antibody to tyrosine hydroxylase (TH), the rate-limiting enzyme in the
      biosynthesis of dopamine, and immunohistochemical procedures were used in this
      study to compare the numbers of TH-immuno-positive neurons observed in the
      arcuate nuclei of Ames dwarf mice compared to phenotypically normal mice of the
      same strain. In female dwarfs, the number of TH-immunopositive neurons in the
      arcuate nuclei but not the pars compacta was markedly reduced when compared to
      normal females. The elevation of circulating PRL either by the implantation of a
      normal pituitary under the kidney capsule or by the daily administration of ovine
      PRL increased the numbers of arcuate neurons which expressed immunochemically
      detectable TH to a level comparable to that observed in untreated normal mice.
      The number of TH-expressing neurons was also reduced in the arcuate nuclei of
      dwarf males although the deficiency was not as great as in females. Ovine PRL
      seemed to have little effect on the numbers of TH-immunopositive neurons observed
      in either dwarf or normal male mice. These results suggest that the postnatal
      absence of PRL in mice does not result in a major reduction in the total
      population of TIDA neurons. Rather these neurons appear to be present in nearly
      normal numbers but are in a dormant state in the absence of circulating PRL.

PMID- 1975654
TI  - Modulation of phosphoinositide metabolism in rat brain slices by excitatory amino
      acids, arachidonic acid, and GABA.
AB  - In rat brain slices the synthesis of [3H]phosphoinositides and the production of
      [3H]inositol monophosphate (IP1) induced by norepinephrine (NE) were inhibited by
      glutamate. Calcium concentrations were varied to test if these inhibitory effects
      of glutamate were mediated by a calcium-dependent process. Although reducing
      calcium or addition of the calcium antagonist verpamil reduced the inhibitory
      effects of glutamate, these results were equivocal because reduced calcium
      directly decreased agonist-induced [3H]phosphoinositide synthesis. The inhibitory
      effects of glutamate were mimicked by quisqualate in a dose-dependent manner, but
      none of a variety of excitatory amino acid receptor antagonists modified the
      inhibition caused by quisqualate. It is suggested that glutamate activates a
      quisqualate-sensitive receptor (for which an antagonist is not available) and
      causes inhibition of phosphoinositide hydrolysis mediated in part by a direct or
      indirect inhibitory effect of calcium on phosphoinositide synthesis. Modulatory
      effects of arachidonic acid were examined because glutamate and calcium can
      activate phospholipase A2. Arachidonic acid caused a rapid and dose-dependent
      inhibition of [3H]phosphoinositide synthesis and of NE-stimulated [3H]IP1
      production. A similar inhibition of the response to carbachol also occurred. The
      inhibition caused by arachidonic acid was unchanged by addition of inhibitors of
      cyclooxygenase or lipoxygenase. Activation of phospholipase A2 with melittin
      caused inhibitory effects similar to those of arachidonic acid. Inhibitors of
      phospholipase A2 were found to impair phosphoinositide metabolism, likely due to
      their lack of specificity for phospholipase A2. Further studies were carried out
      in slices that were prelabelled with [3H]inositol in an attempt to separate
      modulatory effects on [3H]phosphoinositide synthesis and agonist-stimulated
      [3H]IP1 production. Several excitatory amino acid agonists inhibited NE
      stimulated [3H]IP1 production. This inhibitory interaction could be due to
      impaired synthesis of [3H]phosphoinositides because, even though the slices were
      prelabeled, addition of unlabelled inositol reduced NE-stimulated [3H]IP1
      production, indicating that continuous regeneration of [3H]phosphoinositides is
      required. In contrast to the inhibitory effects of the excitatory amino acids,
      gamma-aminobutyric acid (GABA) enhanced the response to NE in cortical and
      hippocampal slices. GABA also enhanced the response to carbachol in hippocampal
      and striatal slices and to ibotenic acid in hippocampal slices. Baclofen
      potentiated the response to NE similarly to the effect of GABA and baclofen
      partially blocked the inhibitory effect of arachidonic acid but did not alter
      that of quisqualate.

PMID- 1975655
TI  - Presynaptic facilitation of glutamate release from isolated hippocampal mossy
      fiber nerve endings by arachidonic acid.
AB  - Hippocampal mossy fiber synaptosomes were used to investigate the role of
      arachidonic acid in the release of endogenous glutamate and the long-lasting
      facilitation of glutamate release associated with long-term potentiation.
      Exogenous arachidonate induced a dose-dependent efflux of glutamate from the
      hippocampal mossy fiber synaptosomes and this effect was mimicked by melittin.
      Neither treatment induced the release of occluded lactate dehydrogenase at the
      concentrations used in these experiments. In each case, removal of the
      biochemical stimulus allowed for glutamate efflux to return to spontaneous
      levels. However, there was a persistent effect of exposure to either arachidonate
      or melittin, since these compounds facilitated the glutamate release induced by
      the subsequent addition of 35 mM KCl. This facilitation of glutamate release
      resulted from an enhancement of both the magnitude and duration of the response
      to depolarization. Although exogenous prostanoids were also able to stimulate the
      release of glutamate, they appeared to play no direct role in secretion
      processes, since inhibition of eicosanoid synthesis potentiated the glutamate
      efflux in response to membrane depolarization or exogenous arachidonic acid. We
      suggest that the calcium-dependent accumulation of arachidonic acid in
      presynaptic membranes plays a central role in the release of endogenous glutamate
      and that the persistent effects of arachidonic acid may be related to the
      maintenance of long-term potentiation in the hippocampal mossy fiber-CA3 synapse.

PMID- 1975657
TI  - Peripubertal changes in the nature of the GnRH response to alpha-adrenoceptor
      stimulation in vitro and their modulation by testosterone.
AB  - Adrenergic mechanisms have been widely implicated in the regulation of GnRH
      secretion in adult rats but their role in young animals, in which the activity of
      the GnRH neurones is minimal, is unclear. These experiments were done to examine
      the effects of alpha-adrenoceptor stimulation on the secretion in vitro of GnRH
      by hypothalami from immature and adult male rats. The alpha 1-adrenoceptor
      agonist, phenylephrine (10(-9) - 10(-7) M), stimulated release of GnRH from
      hypothalami from adult (200 g) and peripubertal (150 g) rats but inhibited
      markedly the secretion of the releasing factor from the limited stores available
      in hypothalami from immature (50 or 100 g) rats. The stimulatory and inhibitory
      responses to phenylephrine, evident in adult and younger rats respectively, were
      concentration-dependent and antagonized readily by the selective alpha 1
      adrenoceptor antagonist, alfuzosin (10(-6) M), but not by the beta-adrenoceptor
      antagonist, propranolol (10(-6) M). Hypothalami from 14-day castrated adult rats,
      in which the serum LH was elevated and hypothalamic GnRH content reduced,
      responded to alpha 1-adrenoceptor stimulation in vitro, like those from immature
      rats, with a marked reduction in GnRH release. In contrast, hypothalami from
      corresponding castrates bearing testosterone implants, which maintained the
      hypothalamic GnRH content and serum LH and testosterone concentrations at levels
      similar to those of intact controls, exhibited the normal 'adult' response to
      phenylephrine. Studies utilizing 3H-prazosin indicated that the number (Bmax) of
      hypothalamic alpha 1-adrenoceptor binding sites increases at puberty but that
      receptor affinity (KD) is unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1975658
TI  - Transitory inner medullary nerve terminals in the cat kidney.
AB  - An indirect immunohistochemical method was used to visualize nerves
      immunoreactive for tyrosine hydroxylase (THI) and dopamine-beta-hydroxylase
      (DBHI) in kidney sections of cats 6 weeks and 2 and 3 months of age. THI and DBHI
      nerve terminals innervate the renal pelvis, interlobar veins and arterial tree
      including medullary vascular bundles of cats of each age studied. In kidneys of 6
      week-old cats, THI and DBHI axons form elaborate plexuses that are distributed
      throughout much of the inner medulla, whereas some medullary axons appear to
      degenerate at 2 months and no inner medullary plexuses were visualized in 3-month
      old cats. Transitory inner medullary nerves in the cat kidney may influence
      cellular development and play a role in salt and water balance.

PMID- 1975659
TI  - Whole-cell patch-clamp recordings of an NMDA receptor-mediated synaptic current
      in rat hippocampal slices.
AB  - Whole-cell patch-clamp recordings and pharmacological techniques have been used
      to obtain low noise recordings of 2 excitatory postsynaptic synaptic currents
      (termed EPSCA and EPSCB) evoked by stimulation of the Schaffer collateral
      commissural pathway in rat hippocampal slices. EPSCA was blocked by 6-cyano-7
      nitroquinoxaline-2,3-dione (CNQX) and EPSCB was blocked by D-2-amino-5
      phosphonovalerate (APV), indicating their mediation by non-N-methyl-D-aspartate
      (non-NMDA) and NMDA receptors, respectively. EPSCB has a slower time-course than
      EPSCA and its current-voltage relationship was highly non-linear with a region of
      negative slope conductance from -35 to -100 mV. These properties of EPSCA and
      EPSCB can explain their differing participation in synaptic transmission in this
      pathway.

PMID- 1975660
TI  - The glycine site modulates NMDA-mediated changes of intracellular free calcium in
      cultures of hippocampal neurons.
AB  - Recent evidence indicates that the N-methyl-D-aspartate (NMDA) receptor-channel
      complex contains a glycine subunit whose activation may be necessary for channel
      operation. It has been previously shown that stimulation of the NMDA receptor
      leads to an increase in intracellular ionic Ca2+ [( Ca2+]i); therefore, we
      examined the role of the NMDA receptor-associated glycine site in modulating
      [Ca2+]i using the fluorescent dye Fura II in hippocampal neuron cultures. A 3-s
      pulse of 200 microM NMDA resulted in a mean [Ca2+]i increase of 363 nM above the
      average resting concentration of 122 nM. Perfusion of the glycine site antagonist
      7-chlorokynurenate (Cl-Kyn) essentially eliminated the NMDA-induced alteration in
      [Ca2+]i. Either 40 microM glycine or 50 microM D-serine completely reversed the
      effect of Cl-Kyn, indicating that the drug was acting at the glycine site. The
      NMDA receptor antagonists 2-amino-5-phosphonovalerate (AP5) and ketamine, which
      bind to the glutamate recognition site and the ion channel, respectively, also
      blocked the NMDA-mediated [Ca2+]i response; however, glycine or D-serine did not
      reverse this effect. These data show that the glycine binding site coupled to the
      NMDA receptor modulates the NMDA-mediated increase in [Ca2+]i. Antagonists of the
      glycine site provide a new tool to investigate and possibly control
      neuroplasticity and neurotoxicity related to the NMDA receptor complex.

PMID- 1975661
TI  - Beta blocker dose-titration in the drug treatment of hypertension.

PMID- 1975662
TI  - Markedly reduced activity of lysyl oxidase in skin and aorta from a patient with
      Menkes' disease showing unusually severe connective tissue manifestations.
AB  - In Menkes' disease, a severe disturbance of copper handling appears to render
      copper unavailable for copper-requiring processes. We have measured the activity
      of lysyl oxidase, the copper-dependent enzyme that initiates the cross-linking of
      collagen and elastin, in extracts of skin and aorta obtained at autopsy from a
      patient with unusually marked connective tissue manifestations, and found it to
      be only 6-12% of normal, thus suggesting a basis for these alterations.

PMID- 1975663
TI  - [A case of periarteritis nodosa in an 8-month-old child].

PMID- 1975665
TI  - repa, a repetitive and dispersed DNA sequence of the filamentous fungus Podospora
      anserina.
AB  - The sequences of homologous DNA regions of two wild-type strains of the fungus
      Podospora anserina, revealed in one strain the presence of a 349bp insertion
      leading to a RFLP. This DNA sequence is repeated in the genome and some of its
      locations are different in various wild-type strains. This DNA element exhibits
      structural similarities with the yeast solo delta, sigma or tau elements.

PMID- 1975666
TI  - Polymorphism at the D20S13 (p phi 64) locus.

PMID- 1975664
TI  - Identification and characterization of a Dictyostelium discoideum ribosomal
      protein gene.
AB  - We have identified a developmentally repressed large-subunit ribosomal protein
      gene of Dictyostelium discoideum based on sequence similarity to other ribosomal
      proteins. Protein rpl7 is homologous to large subunit ribosomal proteins from the
      rat and possibly to Mycoplasma capricolum and Escherichia coli, but is not
      similar to three sequenced ribosomal proteins in Dictyostelium. The rpl7 gene is
      present at one copy per genome, as are six other cloned Dictyostelium ribosomal
      proteins. Restriction fragment length polymorphisms exist for ribosomal protein
      genes rpl7, rp1024, and rp110 in strain HU182; most Dictyostelium ribosomal
      protein genes examined are linked no closer than 30-100 kb to each other in the
      genome. Dictyostelium ribosomal proteins are known to be developmentally
      regulated, and levels of rpl7 transcript gradually decrease during the 24-hour
      development cycle. This drop correlates with that of rp1024, indicating these and
      other ribosomal protein genes may be coordinately regulated. To determine the
      cellular location of the protein, we raised antibodies to an rpl7-derived
      branched synthetic peptide. These antibodies cross-reacted with one protein of
      the expected size in a ribosomal protein fraction of Dictyostelium, indicating
      that the product of gene rpl7 is localized in the ribosome.

PMID- 1975667
TI  - Two EcoRI RFLPs at the GLUT2 locus.

PMID- 1975668
TI  - PCR detection of the pKM.19/ScrfI RFLP (D7S23), a marker closely linked to the
      cystic fibrosis mutation.

PMID- 1975669
TI  - Tetranucleotide repeat polymorphism in the LPL gene.

PMID- 1975670
TI  - Three polymorphisms at the D17S29 locus.

PMID- 1975671
TI  - StuI polymorphisms in the vWF gene.

PMID- 1975672
TI  - Two polymorphisms at the D10S94 locus.

PMID- 1975673
TI  - DGGE detection of HhaI polymorphism in the F9 gene.

PMID- 1975674
TI  - Three polymorphisms at the D10S85 locus.

PMID- 1975675
TI  - Codon 72 polymorphism of the TP53 gene.

PMID- 1975676
TI  - RsaI polymorphism in von Willebrand factor (vWF) at codon 789.

PMID- 1975677
TI  - RFLP for a DNA clone which maps to 19q13.2-19qter (D19S63).

PMID- 1975678
TI  - Two RFLPs detected by a cosmid at locus D16S144.

PMID- 1975679
TI  - AccII polymorphism of the p53 gene.

PMID- 1975680
TI  - A stuI RFLP in the human COL11A2 gene.

PMID- 1975681
TI  - Two RFLPs at the glutathione S-transferase 3 gene.

PMID- 1975682
TI  - HincII polymorphism at the D10S95 locus.

PMID- 1975683
TI  - PCR detection of the Tth 111 I RFLP at the RB locus.

PMID- 1975684
TI  - A second NsiI RFLP at the CYBB locus.

PMID- 1975685
TI  - BamHI RFLP at the GLUT3 locus.

PMID- 1975686
TI  - A sequence polymorphism in the 3'-nontranslated region of the pro alpha 1 chain
      of type I procollagen.

PMID- 1975687
TI  - A KpnI DNA polymorphism in the human von Willebrand factor (VWF) gene.

PMID- 1975689
TI  - Reflex sympathetic dystrophy syndrome following trauma to the foot.

PMID- 1975688
TI  - Right atrial myxoma with a nonembolic intestinal manifestation.
AB  - A 5-year-old male with right atrial myxoma without interatrial communication who
      presented with abdominal pain, vomiting, fever, and guaiac positive stool is
      reported. He was later found to have ischemia of a jejunal segment necessitating
      segmental resection. Although his symptoms persisted postoperatively, surgical
      removal of a right atrial myxoma was followed by complete resolution of his
      intestinal symptoms. We demonstrated that the mesenteric vasculitis was of
      nonembolic origin, and we speculate autoimmune arteritis as a possible mechanism.

PMID- 1975690
TI  - Site- and stereospecific ocular drug delivery by sequential enzymatic
      bioactivation.
AB  - Intraocular enzymes convert the ketoxime analogues of some beta-adrenergic
      blockers via a sequential bioactivation process involving hydrolysis to the
      corresponding ketones followed by reduction to the aryloxyaminoalcohols, which
      then exert known and predictable physiological and pharmacological effects only
      at the site of the action--i.e., in the eye--without any systemic side effects.
      The sequential nature of the process is highlighted by the observation that the
      administration of the ketone intermediate also leads to its conversion to the
      beta-adrenergic antagonist, the active compound. The reduction is stereospecific
      resulting in the formation of the more potent S-(-)-form of the drug, thus
      providing prospect to glaucoma treatment. The same activation process of the
      ketoximes does not take place systemically, thus administration of these
      ketoximes does not produce cardiovascular effects.

PMID- 1975691
TI  - Haem-dependent activation of guanylate cyclase and cyclic GMP formation by
      endogenous nitric oxide: a unique transduction mechanism for transcellular
      signaling.
AB  - The interaction between nitric oxide (NO) synthesized in one cell and the haem
      group of cytosolic guanylate cyclase located in target cells to form NO-haem
      guanylate cyclase represents a unique signal transduction mechanism that links
      extracellular stimuli to the synthesis of cyclic GMP in nearby target cells.
      Autacoids, neurotransmitters, and macrophage- and neutrophil-activating factors
      interact with selective extracellular receptors to trigger formation of NO from L
      arginine. NO may be viewed as a second messenger. The NO diffuses into adjacent
      target cells and causes haem-dependent activation of guanylate cyclase, thereby
      stimulating cyclic GMP accumulation. Guanylate cyclase-bound haem serves as a
      transducer in transferring the signal from NO to guanylate cyclase. Cyclic GMP
      acts as a third messenger in causing vascular smooth muscle relaxation,
      inhibition of platelet aggregation and adhesion, and modulation of macrophage,
      neutrophil, and other phagocytic cell functions. The unique physical and chemical
      properties of NO allow it to function as an intercellular modulator within a
      localized environment. This intercellular or transcellular signaling mechanism
      involving a common signal transduction mechanism permits the rapid initiation of
      localized complementary cellular functions leading to increased local blood flow,
      inhibition of local thrombosis, and modulation of phagocytosis and cytotoxicity.

PMID- 1975692
TI  - [Changes in the chromatin structure of the thyroid cells related to the
      expression of the thyroglobulin gene].
AB  - A highly purified thyroglobulin mRNA was isolated from human nodal euthyroid
      goiter. A full-length cDNA was synthesized from 33S RNA by using reverse
      transcriptase in the presence of human placenta ribonuclease inhibitor. A DNA
      complementary to human Tg mRNA was used in liquid hybridization experiments to
      quantify Tg mRNA. The amount of Tg mRNA in euthyroid nodal and congenital goiter
      was reduced. In thyroid cancer Tg specific mRNA was absent. Direct correlation
      between Tg gene expression in thyroid cells and DNAase-I hypersensitivity of
      chromatin from the thyroid gland nucleus was revealed.

PMID- 1975693
TI  - Single base mutation in the type II procollagen gene (COL2A1) as a cause of
      primary osteoarthritis associated with a mild chondrodysplasia.
AB  - A cosmid clone was isolated that contained an allele for the type II procollagen
      gene previously shown to be coinherited with primary generalized osteoarthritis
      in a large family. Affected members of the family had evidence of a mild
      chondrodysplasia, but they developed progressive osteoarthritic changes in many
      joints that had no epiphyseal deformities. The clone contained 52 of the 54 exons
      of the gene. Nucleotide sequencing of greater than 20,000 base pairs from the
      clone demonstrated that all the coding sequences and all the intron-exon
      boundaries were normal except for a single base mutation that converted the codon
      for arginine at position 519 of the alpha 1(II) chain to a codon for cysteine, an
      amino acid not found in type II collagen from humans or a variety of other
      species. The mutation was found in all affected members of the family but not in
      unaffected members or in 57 unrelated individuals.

PMID- 1975694
TI  - DNA polymerases alpha, delta, and epsilon: three distinct enzymes from HeLa
      cells.
AB  - DNA polymerases alpha, delta, and epsilon have been purified and characterized
      from the same HeLa cell extract in order to determine their relationship by
      comparing them from the same cell type. The catalytic properties and the primary
      structures of the large subunits of the DNA polymerases as compared by partial
      peptide mapping with N-chlorosuccinimide are different. Likewise, the small
      subunit of DNA polymerase epsilon appears to be distinct from the large subunit
      of the same polymerase and from the smaller subunits of DNA polymerase alpha.
      HeLa DNA polymerase delta is processive only when HeLa proliferating cell nuclear
      antigen is present, whereas DNA polymerase epsilon is quite processive in its
      absence. Inhibitor and activator spectra of DNA polymerases alpha, delta, and
      epsilon also distinguish the three enzymes. These results and immunologic
      comparisons published elsewhere support the premise that HeLa DNA polymerases
      alpha, delta, and epsilon are distinct enzymes that have common properties with
      yeast DNA polymerases I, III, and II, respectively.

PMID- 1975695
TI  - Development of a class of selective cholecystokinin type B receptor antagonists
      having potent anxiolytic activity.
AB  - PD134308 and PD135158 are potent and selective antagonists at the cholecystokinin
      type B (CCK-B) receptors with IC50 values of 1.6 nM and 3.5 nM, respectively, in
      the radioligand binding assay and Ke values of 7.82 and 12.9 nM, respectively, in
      their blocking action on CCK responses in the rat lateral hypothalamic slice.
      PD134308 and PD135158 produced potent anxiolytic effects in the mouse black/white
      box test after either subcutaneous or oral administration. There was no evidence
      of the development of tolerance to the anxiolytic action of either PD134308 or
      PD135158 in mice treated twice daily for 7 days, nor was there any sign of
      withdrawal anxiogenesis after abrupt termination of this treatment. Both CCK-B
      antagonists were able to suppress the withdrawal anxiogenesis and produce an
      anxiolytic effect in mice previously made tolerant to diazepam. PD134308 and
      PD135158 produced potent anxiolytic effects in the rat elevated plus maze test
      and the rat social interaction test. The effects were comparable in magnitude to
      those seen with diazepam. However, unlike diazepam, PD134308 and PD135158 did not
      produce sedation. The CCK-B antagonists also showed powerful anxiolytic activity
      in the "marmoset human threat test." These results provide evidence of a
      selective role for CCK-B receptors in the control of anxiety. PD134308 and
      PD135158 are members of a class of anxiolytic agents that have a greatly improved
      profile compared with benzodiazepines or serotonin-related anxiolytics.

PMID- 1975696
TI  - Prolactin effects on the dietary regulation of mouse mammary tumor virus proviral
      DNA expression.
AB  - Chronic energy-intake restriction inhibits mouse mammary tumor virus (MMTV)
      induced mammary tumors in C3H/Ou mice by greater than 90%. We have shown that
      associated with suppression of mammary tumorigenesis there is a reduction or
      inhibition of circulating prolactin, MMTV particles expressed, and MMTV mRNA
      transcription in mammary glands (and in most organs tested). To understand the
      concerted action of prolactin, energy-consumption level, and MMTV on inducing
      mammary tumors, experiments were designed to control prolactin and energy levels
      in order to evaluate their effects on MMTV mRNA expression. Mice on restricted
      diets were grafted with adenohypophyses, and mice fed ad libitum were treated
      with the dopaminomimetic agent octahydrobenzo [g]quinoline. Adenohypophyseal
      grafting significantly increased prolactin in dietary (energy)-restricted mice,
      and this effect was associated with an increase in MMTV mRNA expression within
      the mammary gland; a linear correlation between prolactin levels and MMTV mRNA
      expression in the mammary gland was found. Conversely, elimination of the
      nocturnal peak of circulating prolactin by i.p. injection of dopaminomimetic
      octahydrobenzo [g]quinoline to mice fed ad libitum delayed (by 8 weeks) and
      reduced (even as long as 25 weeks) mammary gland MMTV mRNA expression. These
      findings associate prolactin influences with MMTV mRNA production in mice and
      help explain the link between chronic energy-intake restriction and reduced MMTV
      gene expression.

PMID- 1975699
TI  - Perinatal undernutrition reduced ethanol intake preference in adult recovered
      rats.
AB  - Adult female rats submitted to a protein deprivation schedule at perinatal age
      (from 14th day of fetal life until 50 days of age) were tested for alcohol intake
      in a preference test. When compared with control animals, experimental rats
      exhibited higher overall fluid intake. Nevertheless, in terms of ethanol
      preference these subjects evidenced lower preference to this drug. A test for
      assessing ethanol olfactory preference did not show any differences between
      control and experimental rats in basal conditions. However, after repeated
      exposure to alcohol, deprived rats showed an aversion to ethanol odor, while
      controls evidenced the opposite effect, i.e., heightened preference. Possible
      differences to the aversive effects of ethanol between control and experimental
      animals were assayed by means of two taste aversion tests, by associating alcohol
      to sucrose or NaCl. No differences were detected between both groups of rats.
      These results demonstrate that early undernutrition reduces ethanol preference in
      a free choice situation. Such an effect could be due, at least partially, to odor
      aversion developed by repeated exposure.

PMID- 1975700
TI  - [Solder bond quality].

PMID- 1975697
TI  - Permeability of the murine blood-brain barrier to some octapeptide analogs of
      somatostatin.
AB  - Analogs of somatostatin are being investigated clinically for the treatment of
      various malignancies, including brain tumors. We studied the ability of three
      therapeutically promising radioactively labeled somatostatin octapeptide analogs,
      RC-160, RC-121, and RC-161, to cross the blood-brain barrier (BBB) after
      peripheral or central injection. After i.v. injection, intact RC-160 was
      recovered from the blood and the brain. The entry rates were different from each
      compound but were generally low. By contrast, entry across the intact BBB
      increased 220 times when RC-160 was given in a serum-free perfusate. This
      suggests that some serum-related factor, probably the previously described
      protein binding or an aggregation-promoting factor, is the main determinant in
      limiting the blood-to-brain passage of somatostatin analogs. Entry into the brain
      was not inhibited by the addition of unlabeled analog to the perfusate, showing
      that passage was probably by diffusion across the membranes that comprise the BBB
      rather than by saturable transport. By contrast, a saturable system was found to
      transport peptide out of the central nervous system (CNS). The clearance from the
      CNS of RC-160 and RC-121, but not RC-161, was faster than could be accounted for
      by reabsorption of cerebrospinal fluid. Transport of radioactively labeled RC-160
      out of the CNS was inhibited by unlabeled RC-160 or somatostatin but was not
      affected by some other peptide known to cross the BBB by their own transport
      systems. More than 80% of the radioactivity recovered from the blood after
      intracerebroventricular injection of RC-160 was eluted by HPLC at the position of
      the labeled analog, showing that the peptide had crossed the BBB in intact form.
      Our results indicate the presence of a saturable transport system in one
      direction across the BBB for some superactive analogs of somatostatin.

PMID- 1975698
TI  - Multiple neuroendocrine responses to chronic social stress: interaction between
      individual characteristics and situational factors.
AB  - After four weeks of individual housing, male Wistar rats (selected for high or
      low spontaneous aggressiveness by multiple round-robin encounters) were housed
      three per cage and submitted to four weeks of chronic social stress consisting of
      changing membership in the social groups by daily rotation of the animals among
      cages every day according to a random permutation procedure. In addition, half
      the males in each condition were housed with three females. Each environmental
      condition triggered different neuroendocrine changes. Cohabitation with females
      increased the hypothalamo-pituitary-adrenocortical axis activity, including
      enlargement of adrenals and increased circulating corticosterone levels. On the
      other hand, daily rotation of the rats between different social groups activated
      part of the sympathetic nervous system, such as increased phenylethanolamine N
      methyl transferase (PNMT) activity in the adrenals. The level of aggressiveness,
      however, had no direct influence but interacted with environmental factors on
      such neuroendocrine measures as circulating testosterone or plasma renin
      activity. These results indicate that during chronic stress, there is no single,
      unique response by the animal, but a highly complex set of neuroendocrine
      changes, dependent on the interaction between individual characteristics (the
      level of aggressiveness is an example) and situational factors.

PMID- 1975701
TI  - [Solder bond quality. 2. Bend test, elastic model and metal bond].

PMID- 1975702
TI  - Gamma-glutamyl transpeptidase and acetylcholinesterase activities in brain
      capillaries of cholesterol-fed rabbits.
AB  - Cerebral microvascular endothelium, the constituent cell of the blood-brain
      barrier, is enriched in the enzyme gamma-glutamyl transpeptidase (GGT). This
      enzyme plays a role in the regulation of amino acid uptake and transport, and in
      the gamma-glutamylation of serotonin, dopamine and norepinephrine. Recent studies
      have demonstrated that GGT activity is modulated by cholinergic-adrenergic
      agonists. The levels of the acetylcholine-catabolizing enzyme
      acetylcholinesterase (AChE), may therefore be related to the modulation of the
      GGT activity. In this study, the activities of GGT and AChE in microvessel
      enriched fractions were assayed after feeding of rabbits a high cholesterol diet.
      A 21% decrease of GGT activity and a 44% increase of AChE activity appeared at
      the end of dietary treatment.

PMID- 1975703
TI  - Impromidine-induced changes in the permeability of the blood-brain barrier of
      normotensive and spontaneously hypertensive rats.
AB  - Previous studies suggested histamine receptors mediate changes in the
      cerebrovascular permeability of rats. To test this, we investigated the effects
      of impromidine, a specific agonist at the histamine H2-receptor, on blood
      pressure and permeability of the blood-brain barrier (BBB). Impromidine produced
      dose-dependent hypotension in Wistar-Kyoto (WKY) and spontaneously hypertensive
      (SHR) rats. Two higher doses of impromidine increased BBB permeability to 99mTc
      sodium pertechnetate in WKY rats; however, two lower doses decreased permeability
      in SHR rats. All doses of impromidine increased cerebrovascular permeability to
      131I-labeled serum albumin in both species. Doses of the drug were 100 times
      greater than those required to produce similar alterations using histamine.

PMID- 1975704
TI  - Beta-receptor blocking treatment in portal hypertension.

PMID- 1975705
TI  - Alteration of alpha 1 Na+,K(+)-ATPase 86Rb+ influx by a single amino acid
      substitution.
AB  - The sodium- and potassium-dependent adenosine triphosphatase (Na+,K(+)-ATPase)
      maintains the transmembrane Na+ gradient to which is coupled all active cellular
      transport systems. The R and S alleles of the gene encoding the Na+,K(+)-ATPase
      alpha 1 subunit isoform were identified in Dahl salt-resistant (DR) and Dahl salt
      sensitive (DS) rats, respectively. Characterization of the S allele-specific
      Na+,K(+)-ATPase alpha 1 complementary DNA identified a leucine substitution of
      glutamine at position 276. This mutation alters the hydropathy profile of a
      region in proximity to T3(Na), the trypsin-sensitive site that is only detected
      in the presence of Na+. This mutation causes a decrease in the rubidium-86 influx
      of S allele-specific sodium pumps, thus marking a domain in the Na+,K(+)-ATPase
      alpha subunit important for K+ transport, and supporting the hypothesis of a
      putative role of these pumps in hypertension.

PMID- 1975706
TI  - Dietary iron overload in southern African rural blacks.
AB  - A survey conducted in rural southern African black subjects indicated that
      dietary iron overload remains a major health problem. A full blood count,
      erythrocyte sedimentation rate, serum concentrations of iron, total iron-binding
      capacity, ferritin, C-reactive protein (CRP), gamma-glutamyltransferase (GGT) and
      serological screening for hepatitis B and human immunodeficiency virus (HIV)
      infections were carried out in 370 subjects (214 inpatients and 156 ambulatory
      Mozambican refugees). The fact that the geometric mean (SD range) serum ferritin
      concentration was much higher in the male hospital patients than in subjects
      living in the community [1,581 micrograms/l (421-5,944 micrograms/l) and 448
      micrograms/l (103-1,945 micrograms/l) respectively] suggested that dietary iron
      overload was not the only factor raising the serum ferritin concentration. The
      major additional factor appeared to be inflammation, since the geometric mean (SD
      range) serum CRP was significantly higher in male hospital patients [21 mg/l (8
      53 mg/l)] than in subjects in the community [3 mg/l (1-5 mg)]. Alcohol ingestion,
      as judged by history and by serum GGT concentrations, was also associated with
      significantly raised serum ferritin concentrations. This finding was ascribed to
      the fact that traditional brews are not only associated with alcohol-induced
      hepatic damage but are also a very rich source of highly bio-available iron. The
      role of iron overload in the genesis of the raised serum ferritin concentrations
      are confirmed in the diagnostic liver biopsy study. The majority of biopsies
      showed heavy siderosis, with varying degrees of hepatic damage.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1975707
TI  - [Infection with the human immunodeficiency virus, rheumatic pathology and
      autoimmunity].

PMID- 1975709
TI  - The conception, birth and childhood of WFUMB and its specialist and continental
      federations: the first quarter century.

PMID- 1975708
TI  - Individual identification of human bloodstains investigated with hypervariable
      DNA loci.
AB  - Seven kinds of hypervariable DNA probes, which recognize hypervariable loci, were
      applied for individual identification of human bloodstains. Allelic frequencies
      and their confidence intervals among unrelated Japanese individuals were
      previously reported from our laboratory, and codominant segregation of the
      polymorphism was confirmed in family studies. One-month-old bloodstains from ten
      individuals were investigated in the present study. The probability of matching
      was calculated using the database among Japanese population. Cumulative
      probability of matching from 7 kinds of hypervariable DNA probes was 1.1 x 10(
      11), which was 4.5 x 10(9) times higher than that from 6 kinds of common blood
      group markers such as ABO, MN, Rh-Hr, P1, Hp and PGM1. Accordingly, DNA
      polymorphism is considered to be informative enough for individual identification
      of bloodstains.

PMID- 1975711
TI  - [The use of monoclonal antibodies for determining the transferrin content of the
      urine].
AB  - The authors used monoclonal antibodies to human transferrin for the development
      of a high-sensitive test system for the assessment of transferrin levels in urine
      with enzyme immunoassay. The conditions of the immunoassay performance were
      optimized. The sensitivity of the test system enabled the authors to define the
      levels of transferrin up to 1 ng/ml. Tests for the detection of transferrin in
      patients with chronic pyelonephritis and chronic renal failure were performed.
      The designed test system permitted transferrin to be revealed in the urine of
      those patients who had negative results during a radial immunodiffusion. The
      authors demonstrated the possibility of using the developed monoclonal antibodies
      in laser nephelometry for the detection of blood and urinary transferrin levels.

PMID- 1975710
TI  - Effect of helium and heliox on glutamate decarboxylase activity.
AB  - The activity of glutamate decarboxylase (GAD) in pure helium at 6.8 MPa was
      significantly enhanced when compared to GAD activity in air at 0.1 MPa (906 vs.
      602 nmol.h-1.mg-1 protein, respectively). No significant difference was found
      between GAD activities in heliox at 6.8 MPa (0.87% O2 at 6.8 MPa) and in air at
      0.1 MPa. On the other hand, the activities in heliox at 0.1 MPa (0.87% O2 at 0.1
      MPa) and air at 0.1 MPa were significantly different (655 and 446 nmol.h-1.mg-1
      protein, respectively). These data indicate that pressures up to 6.8 MPa do not
      affect the GAD-catalyzed synthesis of gamma-aminobutyric acid, but that the
      enzyme, as previously reported, is sensitive to low levels of oxygen.

PMID- 1975712
TI  - [The efficacy of psychotherapy in duodenal peptic ulcer].
AB  - As a result of examining 276 patients with duodenal ulcer the leading
      psychopathogenic variants of the disease were established. Inclusion of
      psychotherapy into multimodality treatment of patients with duodenal ulcer led to
      the reduction of anxious-depressive disturbances, accelerated the cessation of
      the painful and dyspeptic syndromes, lowered the ergotropic activity of the
      neurohormonal systems. Normalization of adrenalin excretion served as an
      indicator of favourable prognosis. Psychotherapy turned out less effective in
      patients with hypochondriac fixations and affective rigidity.

PMID- 1975713
TI  - [The serotoninergic mechanisms of anxiety and the action of tranquilizers (a
      review)].

PMID- 1975714
TI  - Intravenous glutamate enhances edema formation after a freezing lesion.
AB  - The effect of intravenous infusion of glutamate on edema formation after a
      freezing lesion in rats is reported. Twenty-four hours of continuous intravenous
      glutamate application led to a significant increase of hemispheric swelling, and
      of the water and sodium content as compared with animals receiving infusions of
      physiological saline after trauma. The results suggest that glutamate entering
      the e.c. space together with the edema fluid causes additional cytotoxic edema as
      a consequence of an enhanced glutamate uptake by the glia. Therefore, the use of
      amino acid infusions containing glutamate for parenteral nutrition may present an
      additional risk for neurosurgical patients with a disturbed BBB.

PMID- 1975715
TI  - Ionic concentration of shifting fluid during glutamate-induced swelling of
      cultured glioma cells estimated by the cytocrit technique.

PMID- 1975716
TI  - Nucleotide sequence analysis of the 3' half of the genome of bovine leukaemia
      virus grown in FLK cells.
AB  - The DNA sequence of the env and px (tat) regions of bovine leukaemia virus cloned
      from integrated proviral DNA of the virus producing FLK cell line was determined
      and compared with published sequences cloned from bovine leukaemia virus-induced
      tumours of cattle. The homology of 97% between a Belgian tumour clone and the FLK
      clone was significantly lower than that between a Japanese tumour clone and the
      FLK clone, where less than 1% nucleotide exchanges were observed. The sequences
      of cDNAs synthesized from purified virus RNA material which had been grown in
      different FLK sublines were found completely identical with one another as well
      as with the equivalent FLK proviral DNA sequences.

PMID- 1975717
TI  - Immunoreactivity of the Escherichia coli-synthesized polypeptide derived from a
      short segment of the HIV-1 env gene.

PMID- 1975718
TI  - Isolation of Soldado virus from a seabird (Rissa tridactyla L.) in France.

PMID- 1975719
TI  - Amino acid analysis of selected reversed-phase high performance liquid
      chromatographic peaks of crude and partially purified lysed human leukocyte
      ultrafiltrate.
AB  - Analytic reversed-phase high performance liquid chromatography (RP-HPLC) was
      performed to separate from the crude lysed human leukocyte ultrafiltrate (LLU)
      its partially purified most immunoactive subfraction P2/II in vivo. Under
      conditions used, the highest degree of segregation of both. LLU and P2/II could
      be observed in the first, as well as in the last two fifth of the water-methanol
      gradient. The comparison of the RP-HPLC traces of LLU and P2/II suggests that
      probably some hydrophilic components of LLU have been removed or--at least-
      diminished. The preliminary amino acid analysis (AA) of the selected peaks showed
      that none of them lacks Gly, Ser, and Glu. Of the basic amino acid residues Lys
      has been found with relatively many peaks while hydrophobic as well as aromatic
      amino acids have been represented very modestly. Further study is warranted in
      order to determine better the bearings of presented findings for the in vivo
      situation.

PMID- 1975720
TI  - Thermal inactivation and thermodynamic parameters of the cholera phage "kappa".

PMID- 1975721
TI  - Antibodies to retroviruses of types C and D in female patients with benign and
      malignant mammary tumours.
AB  - The sera of women with benign and malignant mammary tumours were investigated for
      the presence of antibodies to structural proteins of retroviruses types C and D
      by indirect immunoenzyme assay (ELISA) and immunoblotting. Among 89 sera tested 5
      reacted with the RD-114 protein, 2 with SSV, M-7, and bovine leukaemia virus
      proteins. None serum reacted with mouse mammary tumour virus proteins. On the
      basis of these results we conclude that the expression of antibodies to
      structural retrovirus proteins is not specific for mammary cancer.

PMID- 1975722
TI  - Effect of meclomen on production and action of human interferon alpha.
AB  - Meclomen (sodium meclofenamate) is a nonsteroidal anti-inflammatory drug (NSAID)
      with dual inhibition of both cyclooxygenase and lipooxygenase enzymes involved in
      arachidonic acid metabolism. Meclomen at nontoxic levels (10(-5) to 10(-8) mol/l)
      caused a 2-6 fold increase in interferon (IFN) production in lymphocytes induced
      by Sendai virus. This enhancement was observed in the case of all blood donors
      tested. Meclomen at the same concentration range had no effect on the antiviral
      activity of human IFN alpha. However, meclomen did show some enhancement of
      antiproliferative activity of human IFN alpha against human adenocarcinoma lung
      cells. Meclomen (10(-5) mol/l) inhibited intracellular levles of prostaglandin E2
      by over 90% within the first four hours. The results presented here strongly
      suggest that inhibition of intracellular levels of PGE2 has no adverse influence
      upon the antiviral and antiproliferative activities of human IFN alpha.

PMID- 1975723
TI  - The influence of endogenous hypocorticism on the replication of influenza virus
      in the mouse lungs and the production of specific antibodies.
AB  - The replication of pathogenic influenza virus A/PR/8/34 in the lungs and the
      synthesis of virus-neutralizing (VN) and haemagglutination-inhibition (HI)
      antibodies has been studied in mice with endogenous hypocorticism induced by a
      bilateral adrenalectomy. The adrenalectomized mice appeared to be more
      susceptible to influenza infection as compared to the mock-operated ones. This
      was evident from earlier deaths and higher death rate in mice inoculated with 50
      EID50, 1000 EID50, and 6000 EID50 of the virus, respectively. A tendency towards
      decrease of specific antibody titres and the resistance to reinfection with
      influenza virus A/PR/8/34 was also observed.

PMID- 1975724
TI  - Relationship between depression of HBsAg production and DNA synthesis by
      interferons in human hepatoma cell line.
AB  - The influence of different interferons (IFNs) on HBsAg production and DNA
      synthesis was studied in PLC/PRF/5 cells using 30 I.U./ml of natural HuIFN-alpha,
      25 I.U./ml of recombinant HuIFN-alpha 2, and 5 I.U./ml of natural murine IFN
      alpha/beta. All three IFN types inhibited significant inhibitory effect on HBsAg
      production during the second 24 hr-interval following their addition. After 96 hr
      HBsAg production had returned to normal levels. Natural HuIFN-alpha clearly
      depressed cellular DNA synthesis 24 hr after IFN addition which returned to
      normal within the next 24 hr. Recombinant HuIFN-alpha 2 influenced DNA synthesis
      only slightly and the mouse IFN-alpha/beta showed no effect.

PMID- 1975725
TI  - Enterovirus isolation from foetal and placental tissues.
AB  - Four spontaneous abortions and two stillbirth occurred during a prospective
      survey following the teratogenicity of echoviruses in 80 pregnant women selected
      at random from the Antenatal Care Service. Echovirus types 19, 27, and 33.
      Coxsackie B2 and B6 were isolated from placental and foetal tissues (brain,
      liver, kidney, heart, and spleen). The mothers also excreted the virus by faeces
      at least twenty days before abortion and responded serologically, indicating
      active virus infection. Almost all aborted children were anomalous with signs of
      viral infection.

PMID- 1975726
TI  - Junin virus replication in peripheral blood mononuclear cells of patients with
      Argentine haemorrhagic fever.
AB  - To study the relationship of Junin virus (JV) to populations of peripheral blood
      mononuclear cells (PBMC) from patients with Argentine Haemorrhagic Fever (AHF),
      blood samples were obtained during the acute period of disease and cultured as
      total, adherent, and non-adherent cell populations. JV was sequentially sought in
      these cell populations by using an Infectious Centre (IC) assay, whereas free JV
      in the supernatants was evaluated by plaque formation. IC were obtained in
      cultures of total PBMC from 8 out of 19 patients. Maximum numbers of IC showed
      high variation among patients, ranging from 3 to 410 IC per 10(6) viable PBMC. In
      contrast, IC were sporadically demonstrated in the non-adherent cell population.
      The release of JV into culture supernatants was detected only in total PBMC
      cultures, thus in the presence of macrophages. These results demonstrate that
      circulating monocytes (macrophages) are targets for JV replication contributing
      to the viral spread in the acute phase of AHF.

PMID- 1975727
TI  - Coxiella burnetii fails to stimulate human neutrophil superoxide anion
      production.
AB  - This study investigated the release of superoxide anion (O2-) as an indicator of
      the oxidative metabolism of human neutrophils during the phagocytosis of Phase I
      Coxiella burnetti. Human neutrophils were incubated for 1 hr at 37 degrees C with
      opsonized or unopsonized viable Phase I Coxiella burnetii (MOI was 100 : 1) and
      superoxide anion formation was measured by the reduction of ferricytochrome C.
      The data revealed that during its phagocytosis by human neutrophils, C. burnetii
      (opsonized or unopsonized) fails to stimulate superoxide anion production. In
      contrast, the uptake of Staphylococcus aureus or zymosan was accompanied by the
      release of measurable O2-. This release of O2- was abrogated by the addition of
      100 micrograms/ml of superoxide dismutase (SOD). These results suggest that the
      establishment of C. burnetii within neutrophils, as occurs during persistent
      infection, may be due to the failure to stimulate the metabolic burst during
      phagocytosis.

PMID- 1975729
TI  - An attempt to analyse the functional difference between various mumps virus
      strains.
AB  - Enzymatic activity of N-acetylneuraminidase of ten various strains of mumps virus
      was compared. From the viewpoint of their biological properties, these strains
      could be classified as laboratory, neurovirulent, and vaccinal (attenuated) ones.
      The enzymatic activity was evaluated by Scatchard's plot which enables to
      interpret it according to polarity of the cooperativity of enzymes' binding
      sites. Laboratory strains of the mumps virus demonstrated an independent type of
      cooperativity, while vaccinal (attenuated) ones showed a positive type of
      cooperation.

PMID- 1975728
TI  - Prevalence of antibody to human T-lymphotropic virus type-1 (HLTV-1) in
      Australian aborigines, and detection in Indonesian sera.
AB  - The first finding of antibody to human T-lymphotropic virus type 1 in Australia,
      specifically in Australian Aborigines, is reported. The overall results suggest
      that this is a new area to be added to the known endemic areas for this virus.
      Antibody prevalence in each of two widely separated areas was found to be
      approximately 16% in 1977, and in one of these areas this had increased to
      approximately 34% in 1984/86. In this area no antibody to this virus was detected
      in children under 4 years of age.

PMID- 1975730
TI  - To the antigenic classification of some viruses from the tick-borne encephalitis
      complex by monoclonal antibodies.
AB  - Two monoclonal antibodies (MoAb) to the Skalica virus from the tick-borne
      encephalitis (TBE) complex were used to compare Karshi and Royal Farm viruses
      with the Russian spring-summer encephalitis, Central European encephalitis (Hypr
      and Kumlinge strains) Skalica, Langat and Powassan viruses. The first MoAb was
      prepared by fusion of P3NS1 cells with BALB/c mouse spleen cells, immunized with
      the Skalica virus; it was of IgM class and reacted in haemagglutination
      inhibition (HI) test (MoAb type 1). The second MoAb was of IgG class and reacted
      in complement-fixation (CF) test (MoAb type 2). MoAb type 1 reacted in the HI
      test with Russian spring-summer encephalitis (RSSE), Central European
      encephalitis (CEE) virus strains, Skalica and Langat viruses. No reaction was
      observed with Powassan, Karshi, and Royal Farm viruses. MoAb type 2 reacted in
      the CF test with all members of tick-borne encephalitis complex except the
      Powassan, Karshi, and Royal Farm viruses.

PMID- 1975731
TI  - Enzyme immunoassay--a method of serological survey of measles vaccination.
AB  - Enzyme immunoassay (EIA) for detection of antibodies to measles virus designed in
      the Moscow Research Institute of Viral Preparations has proved highly sensitive
      (98%) and specific (100%) as tested in 492 vaccinated children. Comparison of EIA
      and haemagglutination inhibition (HI) test allowed to determine the cut-off value
      of the optical density to be equal to 0.1. The serum dilution 1:10 was found
      appropriate for the screening.

PMID- 1975732
TI  - Violence in the emergency department.

PMID- 1975733
TI  - Contribution of luminal ammoniagenesis to proximal tubule ammonia appearance in
      the rat.
AB  - The contribution of luminal ammoniagenesis in the late proximal convolute tubule
      (PCT) via phosphate-independent glutaminase [gamma-glutamyltransferase (gamma
      GT)] remains controversial. If this pathway is important, it must rely on
      glutamine secretion, because filtered glutamine is reabsorbed in the early PCT.
      The contribution of gamma-GT to luminal ammoniagenesis was tested by use of in
      vivo microperfusion in conjunction with a new microfluorometric assay for
      glutamate. We first confirmed that aspartate completely blocked glutamate uptake
      in the PCT. Furthermore, the gamma-GT inhibitor acivicin completely eliminated
      glutamate entry, showing that passive glutamate entry was negligible. Thus the
      accumulation of glutamate can be used as an estimate of luminal glutamine
      deamidation. L-Phenylalanine was used to inhibit glutamine loss, and hippurate
      was used to stimulate gamma-GT activity; therefore luminal glutamine conversion
      to glutamate was promoted. Perfusing the tubule at 30 nl/min with a solution
      containing 10 mM each of hippurate, phenylalanine, and aspartate resulted in a
      glutamate delivery of 1.08 +/- 0.12 pmol.min-1.mm-1. Ammonia appearance was 10
      fold higher, averaging 11.5 +/- 1.3 pmol.min-1.mm-1 under these same conditions.
      Thus the luminal conversion of glutamine to glutamate via gamma-GT is a small
      component of total ammoniagenesis in this segment.

PMID- 1975734
TI  - Regional localization of renal Na(+)-H+ antiporter: response to respiratory
      acidosis.
AB  - The Na(+)-H+ antiporter of renal brush-border membranes has been well
      characterized and plays a role in adaptation to acidosis. Na(+)-H+ antiporter
      activity has been described in other renal regions, but its kinetics as well as
      its role in adaptation to acidosis are unclear. Thus we measured Na(+)-H+
      antiporter activity in membrane vesicles of outer and inner stripes of outer
      medulla (OSOM and ISOM, respectively) and in plasma membranes from papilla and
      compared it to Na(+)-H+ antiporter activity of the cortex in control and
      hypercapnic rabbits. Chronic hypercapnia (induced by exposure to CO2 for 48 h)
      was associated with significantly higher PCO2 and plasma HCO3- and lower urine pH
      than controls. In control animals, magnitude of Vmax of amiloride-sensitive
      component of Na(+)-H+ antiporter (expressed as fluorescence units.300 micrograms
      protein-1.min-1) was 392.2 +/- 32 in cortex, 115 +/- 9.7 in OSOM, 66.1 +/- 9.4 in
      15-25% (F1) fraction and 118.7 +/- 16.8 in 25-40% (F2) fraction of ISOM,
      respectively, and 79.3 +/- 5.2 in papilla. These values were significantly
      different from each other except between F1 and papilla and F2 and OSOM. The Km
      for Na, however, was not different, suggesting that the renal Na(+)-H+ antiporter
      is basically the same in different renal regions but displays different activity.
      Hypercapnia for 48 h increased significantly the amiloride-sensitive component of
      Na(+)-H+ antiporter by 60% in cortex, 43% in F1, and 29% in papilla but failed to
      alter Vmax in OSOM.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1975735
TI  - Analysis of tricarboxylic acid cycle of the heart using 13C isotope isomers.
AB  - 13C-nuclear magnetic resonance (NMR) spectroscopy provides a new approach to the
      analysis of metabolic pathways, because it detects an interaction between
      adjacent 13C nuclei. Previous models of isotope distribution in the tricarboxylic
      acid cycle were designed for analysis of radioisotope data and did not consider
      the information provided by 13C-13C coupling. A mathematical model of the
      tricarboxylic acid cycle was developed that preserves all isotope isomer
      (isotopomer) information and yields simple relationships between 13C-NMR spectra
      of glutamate and metabolic parameters under steady-state conditions. With the use
      of relative peak areas measured from the spectra of tissues supplied with 13C
      enriched substrate(s), the relative fluxes through both oxidative (acetyl-CoA
      utilization) and nonoxidative (anaplerotic) pathways of the tricarboxylic acid
      cycle can be determined. Furthermore, with the judicious selection of 13C
      labeling patterns in a mixture of substrates, direct substrate competition
      experiments can be performed. The perchloric acid extracts of Langendorff and
      working rat hearts oxidizing 13C-enriched fatty acids or carbohydrates are
      analyzed to illustrate this approach, and the importance of measuring the
      fractional enrichment of the available substrate is demonstrated. The technique
      can of course be used with all tissues, not just heart, and is applicable to the
      analysis of in vivo 13C-NMR spectra.

PMID- 1975736
TI  - [Correction of autonomic hyperreactivity in surgery of children with spastic
      cerebral palsy].
AB  - Cardiovascular system parameters were used to investigate autonomous nervous
      system tone in 97 children with cerebral spastic paralysis during and after
      surgical treatment of contractures and vascular deformities in the lower
      extremities. The investigations have shown that additional protection of the
      autonomous nervous system with gangliolytics promotes to a decrease and
      stabilization of the autonomous nervous system tone. The necessity of an
      objective control over the autonomous nervous system tone in children with
      cerebral spastic paralysis and differentiated tactics of hyperreactivity
      correction with gangliolytics are discussed.

PMID- 1975737
TI  - Comparison of the single dose pharmacokinetics of sulphasalazine in rheumatoid
      arthritis and inflammatory bowel disease.
AB  - The pharmacokinetics of sulphasalazine and its principal metabolites in
      rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) were compared.
      Patients with RA had a significantly greater concentration of plasma
      sulphapyridine than patients with IBD (medians 14.0 micrograms/ml and 7.4
      micrograms/ml respectively). Patients with RA also tended to maintain a higher
      plasma sulphapyridine concentration with time, as determined by the area under
      the curve (AUC), but a lower plasma sulphasalazine AUC than patients with IBD. It
      is suggested that more sulphasalazine may be presented to the lower bowel for
      cleavage to sulphapyridine and 5-aminosalicylic acid in patients with RA than in
      IBD. Patients with RA may also have impaired metabolism of sulphapyridine as a
      consequence of their disease. Together these factors may contribute to higher
      peak circulating sulphapyridine concentrations and may be responsible for the
      higher incidence of side effects of sulphasalazine treatment in patients with RA
      than in patients with IBD.

PMID- 1975738
TI  - Intracerebroventricular bethanechol for Alzheimer's disease. Variable dose
      related responses.
AB  - Five male patients participated in a pilot open-label study of dose-related
      aspects of response to intracerebroventricular bethanechol in Alzheimer's
      disease. No patient had remission of symptoms, but three patients improved
      symptomatically and on tests of memory. Improvement was evident over a restricted
      range of doses for each subject, and symptoms were worse at doses below and above
      the optimal range. There was little overlap in the range of doses producing
      improvement among these three. Two patients had no consistent improvement in
      memory, and agitation, depression, paranoia, and seizures developed during
      treatment. Qualitative differences and variability in dosages producing responses
      complicate the identification of true drug response in the treatment of
      Alzheimer's disease.

PMID- 1975739
TI  - Somatostatin inhibition of Ca2(+)-induced insulin secretion in permeabilized HIT
      T15 cells.
AB  - Somatostatin inhibited Ca2(+)-induced insulin secretion in permeabilized HIT-T15
      cells, albeit with decreased sensitivity relative to intact cells. The inhibitory
      action required the presence of GTP, whereas GDP could not substitute for GTP.
      Pertussis-toxin treatment before cell permeabilization abolished the inhibition
      of secretion. Thus somatostatin, by activating a G-protein, interferes with
      exocytosis distal to the generation of soluble intracellular messengers.

PMID- 1975740
TI  - Thin-layer chromatographic screening program for commonly used beta-blockers.
AB  - This article reports thin-layer chromatographic data (corrected Rf-values; Rcf
      values) of 20 commonly used beta-blockers which are regularly encountered in
      toxicological analysis. Silica gel was used as stationary phase and ten systems
      according to the proposals of the German Research Foundation (Deutsche
      Forschungsgemeinschaft; DFG) were chosen as solvents.

PMID- 1975741
TI  - Evidence for major alterations in the thymocyte subpopulations in murine models
      of autoimmune diseases.
AB  - Thymocytes can be divided into four major subpopulations: CD4+CD8+ (double
      positive), CD4-CD8- (double-negative), CD4+CD8- (CD4+) and CD4-CD8+ (CD8+) cells.
      Recent studies have shown that T-cell development in the thymus progresses as:
      CD4-CD8(-)----CD4+CD8(+)----CD4+ or CD8+ cells. In the present study we
      investigated these and other subpopulations of thymocytes in autoimmune MRL(
      )+/+, MRL-lpr/lpr, C57BL/6-lpr/lpr, BXSB and NZB mice before (1-month old) and
      after (4-6-months old) the onset of lymphadenopathy and autoimmune disease. All
      the autoimmune strains at one month of age and other H-2, sex and age-matched
      controls (C3H, DBA/2, and C57BL/6) demonstrated normal proportions of thymocyte
      subsets with approximately 75% double-positive cells, 5-7% double-negative cells,
      11-15% CD4+ cells and 3-5% CD8+ cells. By 4-6 months of age, MRL(-)+/+ mice
      demonstrated a moderate increase in double-negative cells (approximately 13%) and
      a decrease in double-positive cells (approximately 46%). Interestingly, in the
      presence of the lpr gene, as seen in MRL-lpr/lpr mice, the double-negative cells
      increased to approximately 47% and the double-positive cells decreased to
      approximately 16%. In contrast, 4-6-month-old C57BL/6-lpr/lpr mice failed to
      demonstrate any alterations in the thymocyte subsets thereby suggesting that
      background genes, in addition to the lpr gene, played a role in the thymocyte
      differentiation. BXSB male mice with severe lymphadenopathy behaved very
      similarly to MRL-lpr/lpr mice, inasmuch as their thymus contained approximately
      48% double-negative cells and only approximately 8% double-positive cells. In
      contrast to MRL-lpr/lpr and BXSB strains, NZB mice at 6 or 10 months of age had
      normal composition of thymocyte subsets. In MRL and BXSB animals, although there
      was a significant increase in CD4+ cells (approximately 23-33%), due to a
      consequent increase in CD8+ cells (approximately 11%), the ratio of CD4+:CD8+
      cells remained 2-3:1, similar to that seen in normal mice. Furthermore, using the
      J11d marker expressed by the majority of the double-negative and all double
      positive thymocytes but not by mature functional T cells, we confirmed the above
      findings and demonstrated further that MRL-lpr/lpr mice at 4-6 months of age had
      an increased percentage of J11d- double-negative cells and a decrease in J11d+
      double-negative cells.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1975742
TI  - Restriction fragment length polymorphisms in the major histocompatibility complex
      of the non-obese diabetic mouse.
AB  - The inbred non-obese diabetic (NOD) mouse is a spontaneous model for insulin
      dependent diabetes mellitus (IDDM). As in man and BB rats, IDDM in the NOD mouse
      has an autoimmune aetiology. The disease is controlled by several genes, one of
      which, Idd-1, has been mapped to the major histocompatibility complex (MHC) on
      chromosome 17. However, Idd-1 has not yet been identified. To facilitate the
      identification of Idd-1 we have further analysed the MHC region for restriction
      fragment length polymorphisms and we find that the NOD mouse has a distinct
      haplotype: H-2K1nod Kd A beta nod A alpha d E beta nod TNF-alpha beta. In
      addition, the NOD mouse shows some similarities with the H-2b haplotype in the Q
      region, in that either the Q7 or the Q9 gene seems to be like that in the b
      haplotype and that the Qa2 antigen is expressed, while other parts of this region
      are distinct from the b- as well as the d- haplotype. In contrast, the sister
      strain, the non-obese normal (NON) mouse, derived from the same cataract-prone
      line of mice as the NOD mouse, has an MHC Class I region indistinguishable from
      the b-haplotype, but the MHC Class II region is distinct from the NOD mouse as
      well as the b-, d- and k-haplotype.

PMID- 1975743
TI  - Differential effects of beta-adrenergic agonists on insulin secretion from
      pancreatic islets isolated from rat and man.
AB  - The selective beta 2-adrenergic agonist clenbuterol was ineffective as a stimulus
      for insulin secretion when isolated rat pancreatic islets were incubated with
      glucose at concentrations between 4 and 20 mM. Inclusion of the phosphodiesterase
      inhibitor 3-isobutyl-1-methylxanthine led to potentiation of glucose-induced
      insulin secretion, but did not facilitate stimulation by clenbuterol.
      Furthermore, maintenance of isolated rat islets for up to 3 days in tissue
      culture also failed to result in the appearance of a secretory response to beta
      agonists. By contrast, clenbuterol induced a dose-dependent increase in insulin
      release from isolated human islets incubated with 20 mM glucose. Clenbuterol did
      not increase the basal rate of insulin secretion (4 mM glucose) in human islets.
      Under perifusion conditions, the secretory response of human islets to
      clenbuterol was rapid, of similar magnitude to that seen under static incubation
      conditions and could be sustained for at least 30 min. The increase in insulin
      secretion induced by clenbuterol was inhibited by propranolol, indicating that
      the response was mediated by activation of beta-receptors. In support of this, a
      similar enhancement of glucose-induced insulin secretion was elicited by a
      different beta 2-agonist, salbutamol, in human islets. The results indicate that
      the B cells of isolated rat islets are unresponsive to beta-agonists, whereas
      those of human islets are equipped with functional beta-receptors which can
      directly influence the rate of insulin secretion.

PMID- 1975744
TI  - Regulatory elements of the human vimentin gene: activation during proliferation.
AB  - We investigated the constitution of the vimentin regulatory region through the
      use of cloned deletion mutants and the nucleotide sequence analysis in order to
      determine the elements which are implicated in the various physiological
      stimulations. We report that the vimentin promoter is constituted of a
      juxtaposition of at least 20 different putative regulatory elements illustrating
      the molecular tinkering theory. Fifty-eight motifs were found, representing 20
      different sequences. Each of these mini-elements displays a consensus sequence
      homologous to or closely related to that found in regulatory regions of different
      genes correlated with processes of cell activation and proliferation.

PMID- 1975745
TI  - Distribution of dopamine-immunoreactive neuronal perikarya and fibres in the
      brain of a teleost, Gasterosteus aculeatus L. comparison with tyrosine
      hydroxylase- and dopamine-beta-hydroxylase-immunoreactive neurons.
AB  - The distribution of dopamine in the brain of the teleost Gasterosteus aculeatus
      L. was demonstrated with the indirect peroxidase-antiperoxidase
      immunohistochemical method using highly specific antibodies against a dopamine
      glutaraldehyde-thyroglobulin conjugate. Dopamine-immunoreactive (DAir) neuronal
      somata were observed in all main brain regions. In the forebrain, DAir neurons
      were located in a continuous cell column extending from the caudal part of the
      olfactory bulbs to the preoptic area. The neurons lie lateral to the dorsal (and
      caudally to the subcommissural) portion of the ventral telencephalic area, and
      ventromedial to the central nuclei of the dorsal area. In the diencephalon,
      cerebrospinal fluid-contacting neurons were located in the paraventricular organ
      and in the subependymal layers of the dorsal and caudal zones of the
      periventricular hypothalamus. Small DAir neurons were observed in the
      suprachiasmatic nucleus, in the parvocellular preoptic nucleus and in the
      ventromedial thalamic nucleus, while large perikarya were observed dorsolateral
      to the dorsal zone of the periventricular hypothalamus ('PVO-accompanying
      cells'), in the posterior tuberal nucleus and in the most rostral portion of the
      mammillary bodies. Numerous small DAir neurons were located in the
      periventricular pretectal nucleus. In the brainstem, DAir neurons were observed
      in the isthmus region, in the dorsal raphe nucleus and in the lateral parts of
      the nucleus of the solitary tract. DAir perikarya were also observed in the area
      postrema. Direct comparison with the distribution of tyrosine hydroxylase- and
      dopamine-beta-hydroxylase-immunoreactivity (THir and DBHir) gave the following
      results: THir neurons were found in all areas where DAir neurons were located,
      except for the paraventricular organ and the dorsal and caudal zones of the
      periventricular hypothalamus, which were devoid of THir. DBHir (putatively
      noradrenergic or adrenergic) neurons were observed in the lateral parts of the
      nucleus of the solitary tract, and in the isthmus region. The DBHir neurons in
      the isthmus region, which have previously been shown to be noradrenergic,
      appeared to be identical with the THir and DAir neurons of the same area. DAir
      axons were found in high numbers in most parts of the brain. Especially dense
      innervation was found in the ventrolateral and posterior parts of the dorsal
      telencephalic area, the region surrounding the lateral recesses of the third
      ventricle, the interpeduncular nucleus, the dorsal and median raphe nuclei (the
      rostral raphe nuclei), and in the nucleus of the solitary tract.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 1975746
TI  - A double-blind, placebo-controlled trial of thymostimulin in symptomatic HIV
      infected patients.
AB  - The potential therapeutic efficacy of the thymic hormone preparation,
      thymostimulin (TP1), in HIV infection has been studied in a multi-institutional,
      randomized, double-blind, placebo-controlled trial. Fifty evaluable patients with
      advanced AIDS-related complex (ARC) were injected with TP1 or placebo twice
      weekly for 6 months after 2 weeks of daily injections. The primary endpoint,
      progression to AIDS, was reached in nine TP1- and 11 placebo-treated subjects
      after 1 year. CD4 cell numbers were not affected by administration of the study
      drug. No toxicity was associated with TP1 treatment. We conclude that TP1 is
      ineffective in altering the progress of HIV disease in patients with advanced
      ARC.

PMID- 1975747
TI  - MK-801-induced stereotypy and its antagonism by neuroleptic drugs.
AB  - MK-801 [(+)-5-methyl-10,11-dihydroxy-5H-dibenzo-(a,d)cyclohepten-5,10-imi ne
      hydrogen maleate], which blocks glutamatergic transmission at the NMDA-receptor
      gated ion channel, induced stereotypies which are similar to those found after
      intrastriatal injections of AP-5, e.g. sniffing and locomotion. Tests in familiar
      or unfamiliar environment (non-stressful or stressful situation) did not
      qualitatively change MK-801-induced effects. Haloperidol (0.1 mg/kg, IP) delayed
      the onset and shortened the duration of MK-801 (0.16; 0.33 mg/kg, IP)-induced
      stereotypy whereas clozapine (5 mg/kg, SC) potently antagonized it. However,
      exact quantification of sniffing, measured in an experimental chamber designed
      for this purpose, revealed an antagonism by both drugs, haloperidol as well as
      clozapine. Stereotypy is considered to represent an animal model of
      schizophrenia, and the antagonism of stereotypy with classical (haloperidol) as
      well as with atypical (clozapine) antipsychotic drugs is in accordance with the
      glutamate hypothesis of schizophrenia.

PMID- 1975748
TI  - [Enzymes of the inosinic crossing point in human lymphocytes].
AB  - At the "inosinic branch point", inosinic acid (IMP) can be channelled either to
      guanylic acid (GMP) or to adenylic acid (AMP). The 4 enzymes involved in these
      processes are IMP-dehydrogenase (IMP-DH) and GMP synthetase for the formation of
      GMP and adenylosuccinate (AMP-S) synthetase and lyase for the formation of AMP.
      The Authors study the behavior of these enzymes in peripheral blood lymphocytes
      from normal and leukemic patients. The cells were isolated as previously
      reported. GMP synthetase was assayed with radiochemical method, IMP-DH and AMP-S
      synthetase with a radiochemical method coupled to HPLC, while AMP-S lyase was
      determined following the formation of AMP separated by AMP-S by HPLC, without
      using labelled precursors. Except for GMP synthetase, which was very low, no
      activity was detectable in normal lymphocytes; while AMP-S was absent also in
      leukemic cells, the remaining three activities were well evident. The results
      open the possibility of using the inosinic branch point enzymes as tumor markers.

PMID- 1975749
TI  - [Parameters of tubulo-glomerular function in anesthetized rabbits with acute
      kidney insufficiency].
AB  - We have induced acute renal failure (ARF) in barbiturate anesthetized rabbits,
      through warm ischaemia of 30 or 60 min duration caused by transient bilateral
      occlusion of renal arteries. In this model we have monitored some renal
      performance parameters, before and 4 hours after reperfusion, aiming to
      characterize ARF in this animal species. Glomerular filtration rate (determined
      by the inulin clearance technique) was of 9.74 +/- 0.48 ml min-1 in 4 rabbits
      before injury and declined by 91% (60 min ischemia) during the first reperfusion
      hour. In 6 rabbits undergoing 30 min occlusion, pre-ARF values of 10.70 +/- 0.98
      ml min-1 declined by 47%. In both groups no recovery was observed in the
      following hours. Tubular enzymes (alanine-amino-peptidase, AAP and N-acetyl-beta
      glucosaminidase, NAG) were released into urines before injury at the rate of 1.11
      +/- 0.18 and 1.32 +/- 0.41 mU min-1, respectively, in the 30 min model (3
      animals/group). During ARF, maximal AAP output was five-fold increased (5.83 +/-
      0.35 mU min-1), whereas NAG was unmodified. On the other hand, renal
      haemodynamics in 5 rabbits did not change after the ischaemic procedure: total
      renal blood flow (44 +/- 5 ml min-1) and renal vascular resistances (225 +/- 26
      Pa ml-min) displayed less than 10% variations throughout the reperfusion period.
      We concluded that ARF in rabbits can be reliably and reproducibly monitored and
      that the pathogenesis of the disease, in our situation, is attributable mainly to
      tubular cell damage and not to impairment of the vascular component of renal
      performance.

PMID- 1975750
TI  - Contribution of exogenous substrates to acetyl coenzyme A: measurement by 13C NMR
      under non-steady-state conditions.
AB  - A method is presented for the rapid determination of substrate selection in a
      manner that is not restricted to conditions of metabolic and isotopic steady
      state. Competition between several substrates can be assessed directly and
      continuously in a single experiment, allowing the effect of interventions to be
      studied. It is shown that a single proton-decoupled 13C NMR spectrum of glutamate
      provides a direct measure of the contribution of exogenous 13C-labeled substrates
      to acetyl-CoA without measurement of oxygen consumption and that steady-state
      conditions need not apply. Two sets of experiments were performed: one in which a
      metabolic steady state but a non-steady-state 13C distribution was achieved and
      another in which both metabolism and labeling were not at steady state. In the
      first group, isolated rat hearts were supplied with [1,2-13C]acetate, [3
      13C]lactate, and unlabeled glucose. 13C NMR spectra of extracts from hearts
      perfused under identical conditions for 5 or 30 min were compared. In spite of
      significant differences in the spectra, the measured contributions of acetate,
      lactate, and unlabeled sources to acetyl-CoA were the same. In the second set of
      experiments, the same group of labeled substrates was used in a regional ischemia
      model in isolated rabbit hearts to show regional differences in substrate
      utilization under both metabolic and isotopic non steady state. This sensitive
      probe of substrate selection was also demonstrated in intact hearts where
      excellent time resolution (3 min) of substrate selection was feasible.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1975751
TI  - Modulation of CD4 expression on lymphoma cells transplanted to mice fed (n - 3)
      polyunsaturated fatty acids.
AB  - Groups of adult AKR mice were fed well defined fats controlled diet regimens.
      These consisted of either saturated (beef tallow: 'BT') or (n - 3)
      polyunsaturated (fish oil: 'FO') fatty acids supplementation to basal mix mouse
      food. In other groups, the basal mix was given without any fat supplement ('NF').
      Six weeks or more after the initiation of these diet regimens, mice received
      intraperitoneal injection of histocompatible RDM-4 lymphoma cells. Ascites RDM-4
      tumors were harvested approximately two weeks later, and some of their
      physicochemical properties were studied. It was repeatedly found that: (1) the
      tumor grew considerably faster in the FO-fed donor than in the BT- or NF-fed
      donors; (2) cell membrane fluidity, content of C20(n - 3) and of C22(n - 3) fatty
      acids were significantly higher in the FO groups than in both BT and NF groups,
      while the content of C20(n - 6) and 22:4(n - 6) fatty acids was concomitantly
      decreased; (3) expression of the CD4 cell surface marker was always significantly
      diminished in the FO groups, whereas other markers such as CD8, H2K, Thy-1 and
      LFA-1 were not affected. Similar results were obtained, whether fats constituted
      from 1% to 16% by weight of the food intake. Use of a recently selected line of
      the RDM-4 lymphoma, exhibiting higher CD4 marker expression, resulted in similar
      observations. On the other hand, CD4 expression on cells from lymphoid organs of
      healthy adult AKR mice was not detectably modulated by the dietary fats.

PMID- 1975752
TI  - The effects of a low extracellular concentration of potassium on the activity and
      numbers of Na+/K+ pumps in an EB-virus transformed human lymphocyte cell line.
AB  - The BM1A EB-virus transformed human lymphocyte cell line contains approximately
      950,000 Na+/K(+)-ATPase sites per cell. The turnover number of each site is
      approx. 2240 molecules of rubidium per min. When cells are exposed to a low
      extracellular concentration of potassium the intracellular concentration of
      sodium rises, and the cells respond in the short term by increasing the Vmax of
      86Rb+ uptake. In the longer term the cells respond by increasing both the Vmax of
      86Rb+ uptake and the Bmax of [3H]ouabain binding. The suggestion that increases
      in the intracellular concentration of sodium is responsible for these changes is
      supported by the finding that monensin, which increases intracellular sodium
      without affecting intracellular potassium, is capable of inducing both the short-
      and long-term changes associated with a low external concentration of potassium.

PMID- 1975753
TI  - Dimerization of the P-glycoprotein in membranes.
AB  - Plasma membranes from a CHO cell line, CHRC5, which exhibits multidrug resistance
      was studied using radiation inactivation analysis. The P-glycoprotein content of
      the membrane was determined by Western blots. Irradiation resulted in the loss of
      P-glycoprotein. The dependence of this loss on radiation dose corresponded to a
      target size of 250 kDa which is the molecular mass of a dimer of the P
      glycoprotein. This is strong evidence to indicate that the P-glycoprotein self
      associates in the membrane.

PMID- 1975754
TI  - Replication of an evoked potential study of lateralized hemispheric dysfunction
      in schizophrenics.
AB  - Visual (VEP) and auditory (AEP) evoked potentials (EPs) were measured to
      replicate previous findings concerning lateralized hemispheric dysfunction in
      chronic schizophrenic patients in a new sample. Measures of EP waveform stability
      (Zr') showed greater hemispheric asymmetry in 26 unmedicated chronic
      schizophrenics than in 26 matched nonpatients, and relatively lower left and
      right hemisphere values in schizophrenics. Similar hemispheric differences were
      not found between medicated patients and matched nonpatients; medication was
      associated with higher left and lower right hemisphere stability. EP amplitudes
      were lower with medications, the lowest amplitudes found in patients receiving
      nonphenothiazine or nonpiperazines as opposed to phenothiazine-piperazine drugs.
      Medications were associated with amplitude asymmetries not observed in
      unmedicated patients. This study confirms greater than normal hemispheric
      asymmetry of VEP and AEP waveshape stability measures in chronic schizophrenics,
      and lower left than right hemisphere stability suggesting left hemisphere
      dysfunction. Alteration of EP asymmetries by antipsychotic medications suggests
      that medication effects may obscure evidence of lateralized dysfunction in
      schizophrenics.

PMID- 1975756
TI  - Paranoid states: classification and management.
AB  - In terms of both nosology and treatment the paranoid states have long proved a
      thorny but irresistible enigma to psychiatrists. Recent evidence suggests that at
      least one of these conditions, paranoia, not only may be eminently treatable, but
      also merits serious consideration as a clinical entity distinct from other
      functional psychoses.

PMID- 1975755
TI  - Effect of dietary cadmium and/or copper on the bone lysyl oxidase in copper
      deficient rats relative to the metabolism of copper in the bone.
AB  - Effects of cadmium (Cd) on lysyl oxidase activity and copper (Cu) metabolism in
      bone were studied using Cu-deficient rats supplemented with Cu and/or Cd in a
      diet. When fed for 8 weeks on a diet containing 0.3 ppm or less Cu (-Cu diet),
      weanling rats revealed anemia, and markedly decreased plasma ceruloplasmin
      activity and serum Cu to less than 15% of normal level, showing features of Cu
      deficiency. These rats were divided into four groups and refed for another 2
      weeks on the following diets: Group I, -Cu diet; Group II, -Cu diet with 50 ppm
      Cd (+Cd diet); Group III, -Cu diet supplemented with 15 ppm Cu (+Cu diet); group
      IV, -Cu diet with both Cu and Cd (+Cu/+Cd diet). After 2 weeks, serum Cu levels
      of Groups I, II, III and IV were 1.8, 0.8, 78 and 74% of the normal control level
      (1.438 +/- 0.060 micrograms/ml), respectively. Concentrations of Cu in epi- and
      metaphyses of the control group, Groups I, II, III and IV were 1.45 +/- 0.20,
      0.67 +/- 0.08, 0.76 +/- 0.12, 1.40 +/- 0.31 and 1.22 +/- 0.05 micrograms/g wet
      tissue, in that order. Concentrations of Cd in epi- and metaphysis increased in
      only Groups II and IV and were 0.15 +/- 0.03 and 0.18 +/- 0.01 micrograms/g wet
      tissue, respectively. Thus, having both Cd and Cu supplements in a diet did not
      inhibit each other's uptake into the tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1975757
TI  - Reduction in antipsychotic drug dosage in mentally handicapped patients. A
      hospital study.
AB  - An investigation in a large mental handicap hospital revealed that 24% of the in
      patients were receiving antipsychotic drugs. Chlorpromazine and thioridazine
      prescriptions accounted for 62% of the total while 10% of patients received depot
      preparations. Fifty-five per cent of the patients receiving these drugs had no
      established psychiatric diagnosis; most of these could be categorised as having a
      behaviour disorder. Patients aged 30-50 received higher doses, and female
      patients received a significantly higher mean dosage than male ones. In the
      patients receiving neuroleptic drugs who had also been taking them four years
      previously, there was a significant reduction in the dosage of the drugs received
      and the extent of polypharmacy of these agents. A mandatory requirement to review
      all prescriptions annually, implemented in 1984, may be a reason for this.

PMID- 1975758
TI  - Localisation of a susceptibility locus for schizophrenia on chromosome 5.
AB  - "A considerable proportion of the variance in the liability to develop
      schizophrenia may be genetic, but segregation analysis, to establish a mode of
      transmission, has not produced a consistent result. One of these studies was
      carried out in Iceland and made use of the large family size and extensive
      genealogical information present in that country. Here we demonstrate genetic
      linkage of two DNA polymorphisms on the long arm of human chromosome 5 to
      schizophrenia in seven British and Icelandic families with multiple affected
      members. The results indicate the existence of a gene locus with a dominant
      schizophrenia-susceptibility allele. Inheritance of the allele in the families
      studied suggests that it may also predispose to psychiatric conditions such as
      schizophrenia spectrum disorders and a variety of other disorders. This report
      provides the first strong evidence for the involvement of a single gene in the
      causation of schizophrenia."

PMID- 1975759
TI  - Biperiden and piroheptine do not affect the serum level of zotepine, a new
      antipsychotic drug.
AB  - The effects of biperiden and piroheptine on the serum level of zotepine were
      studied in 15 schizophrenic and 6 mentally retarded in-patients. Neither of these
      anticholinergic drugs affected the serum level of zotepine nor caused significant
      side-effects. In the schizophrenics the total scores on the BPRS did not change
      significantly with either combination of drugs.

PMID- 1975760
TI  - Prediction of response to electroconvulsive therapy. Preliminary validation of a
      sign-based typology of depression.
AB  - In an open study of 35 depressed patients, psychomotor disturbance, assessed by
      the CORE rating system, significantly predicted response to ECT in patients with
      a 'retarded' but not those with an 'agitated' type of illness. In multivariate
      analyses, psychomotor disturbance was the sole predictor of response. This
      preliminary study suggests that the CORE system, which has been shown to
      differentiate endogenous and non-endogenous depressive disorders, has predictive
      validity in relation to ECT response.

PMID- 1975761
TI  - Glycine synergistically potentiates the enhancement of LTP induced by a
      sulfhydryl reducing agent.
AB  - Two selective modulators of N-methyl-D-aspartate (NMDA) receptor function,
      dithiothreitol (DTT) and glycine, each dramatically enhanced long-term
      potentiation (LTP) in area CA1 of the hippocampus slice. Glycine synergistically
      potentiated the effect of DTT. Kynurenate, but not strychnine, antagonized the
      modulatory effect of glycine on LTP, while 2-amino-5-phosphonovalerate blocked
      LTP in all cases. Neither oxidation with 5-5-dithio-bis-2-nitrobenzoic acid nor
      exposure to the oxidized form of DTT had any effect on LTP. These data suggest
      that in vivo the reducing potential of local environments may interact with
      endogenous glycine to regulate NMDA receptor function.

PMID- 1975762
TI  - Androgen-dependent vasopressinergic neurons are involved in social recognition in
      rats.
AB  - Socal recognition of juvenile conspecifics by adult male rats has been shown to
      be modulated by vasopressin. Because part of the extrahypothalamic
      vasopressinergic innervation of the brain is androgen-dependent, the present
      experiments were undertaken to assess possible interactions between androgens and
      vasopressin in social recognition. Castrated male rats displayed a temporary
      disruption of social recognition when they were tested 1 week after surgery.
      There was no impairment, however, when they were tested every other day following
      surgery. The peripheral injection of a vasopressor antagonist of vasopressin,
      dPTyr(Me)AVP (30 micrograms/kg) impaired social recognition in normal male rats
      but was ineffective in castrated ones. This was not due to an effect of
      castration on the basic pharmacological properties of dPTyr(Me)AVP since the
      antagonist peptide was still able to block the facilitating effects of
      vasopressin on social recognition in castrated male rats. Implantation of a
      testosterone-filled capsule in castrated male rats restored sensitivity of social
      recognition to the action of the vasopressin antagonist. These results suggest
      that androgen-dependent vasopressinergic neurons are physiologically involved in
      the modulation of social recognition in male rats.

PMID- 1975763
TI  - The effects of intranigral GABA and dynorphin A injections on striatal dopamine
      and GABA release: evidence that dopamine provides inhibitory regulation of
      striatal GABA neurons via D2 receptors.
AB  - The effects of injections of gamma-aminobutyric acid (GABA) and dynorphin A into
      the substantia nigra, pars reticulata on the levels of extracellular dopamine
      (DA) and GABA in the ipsilateral striatum of halothane-anaesthetized rats were
      studied using microdialysis. The effects of intranigral injections of substance P
      and neurokinin A were also studied. Intranigral GABA (300 nmol) or dynorphin A
      (0.5 nmol) injections produced a simultaneous decrease in DA and increase in GABA
      levels, while intranigral substance P (0.07 nmol) or neurokinin A (0.09 nmol)
      injections produced an increase in DA but had no effect on GABA levels. DA
      agonists, apomorphine (D1/D2), SKF 38393 (D1) and pergolide (D2) were applied
      locally by perfusing them through the microdialysis probe, each at a
      concentration of 10(-5) M. All 3 agonists decreased the levels of DA in the
      striatum. However, while apomorphine and SKF 38393 increased, pergolide decreased
      the levels of GABA in the striatum. The increase in striatal GABA produced by
      intranigral injections of GABA (300 nmol) was reversed by local perfusion with
      pergolide (10(-5) M), but was not reversed by local perfusion with SKF 38393 (10(
      5) M). These findings suggest that D1 and D2 receptors differentially regulate
      striatal GABA release, and are stimulatory and inhibitory, respectively.
      Furthermore, it is suggested that nigrostriatal DA functions as an inhibitory
      modulator of striatal GABA neurons, acting via D2 receptors.

PMID- 1975764
TI  - Alpha-1-adrenergic receptors in the nucleus tractus solitarii region of rats with
      experimental and genetic hypertension.
AB  - The binding of the alpha 1-adrenergic receptors antagonist, 125I-HEAT, to
      membranes of nucleus tractus solitarii (NTS) regions of the brains of neurogenic
      hypertensive, spontaneously hypertensive (SH), and deoxycorticosterone
      (DOCA)/salt hypertensive rats and their respective controls was studied to
      quantitate the expression of alpha 1-adrenergic receptors. Scatchard analysis of
      the binding studies revealed a 1.8-fold increase in the Bmax of alpha 1
      adrenergic receptors in NTS region membranes of SH rats when compared to their
      Wistar-Kyoto (WKY) control without significant difference in the Kd for 125I
      HEAT. A decrease in the Kd with no difference in Bmax of receptors for 125I-HEAT
      was observed in the NTS region membranes of neurogenic hypertensive rats when
      compared with their sham-operated controls. In contrast, comparison of the Bmax
      and Kd values for 125I-HEAT binding in NTS region membrane of the DOCA/salt
      hypertensive rats and its sham-operated control showed no significant
      differences. We suggest that alterations in baroreceptor afferent activity may be
      related to alterations in central alpha 1-adrenergic receptors binding in SH rats
      and rats with neurogenic hypertension.

PMID- 1975765
TI  - Long-term effect of MPTP in the mouse brain in relation to aging: neurochemical
      and immunocytochemical analysis.
AB  - The long-term effect of the parkinsonism-inducing neurotoxin 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine (MPTP) on central monoaminergic neurons in young (2-3
      months) and aging (12 months) C57BL/6 mice has been studied using neurochemical
      and immunocytochemical techniques. MPTP treatment (4 x 20 mg/kg i.p. given 12 h
      apart) resulted in significant depletion of dopamine (DA) concentration in the
      striatum, substantia nigra, nucleus accumbens, and olfactory tubercle 1 week
      after treatment in both young and aging mice. Although a decreased DA
      concentration in the ventral tegmental area was not seen in young mice, aging
      mice did show a significant decrease. The extent of decrease of DA concentration
      was greater in aging mice than in young mice in all areas investigated except in
      dorsal striatum. The long-term effect of MPTP on DA neurons in young mice
      included considerable recovery of DA concentration in both nigrostriatal and
      mesolimbic DA systems following the initial profound depletion; such recovery was
      minimal in aging mice, even 3 months after MPTP treatment. In young mice treated
      with MPTP, no significant change of norepinephrine (NE) or serotonin (5-HT)
      concentration was observed in any area investigated while a significant decrease
      of NE and 5-HT concentration was seen in several brain areas investigated in
      aging mice. Immunocytochemical analysis revealed that the MPTP injection resulted
      in marked disappearance of tyrosine hydroxylase (TH)-immunoreactive (IR) fibers
      in striatum of both young and aging mice 1 week following treatment. Partial
      recovery of TH-IR fibers was seen 5 weeks or 3 months after MPTP treatment in
      young mice, while no such apparent recovery was seen in aging mice. Aging mice
      also showed significant decrease in the number of TH-positive cell bodies in the
      substantia nigra and ventral tegmental area through all periods investigated,
      while such a significant decrease was only seen in the substantia nigra of young
      mice 1 week after treatment. We conclude that aging mice are more sensitive to
      MPTP and show more widespread damage to the monoaminergic systems than young
      mice, suggesting that MPTP-treated aging mice provide a more useful model for
      studying anatomical and neurochemical characteristics of Parkinson's disease than
      young mice.

PMID- 1975766
TI  - Somatostatin depresses GABA receptor-mediated inhibition in the rat dorsolateral
      septal nucleus.
AB  - The effect of somatostatin-14 (SS-14) on gamma-aminobutyric acid (GABA)-mediated
      inhibitory neurotransmission in the dorsolateral septal nucleus (DLSN) was
      investigated using a submerged slice preparation and intracellular recording
      techniques. Somatostatin-14 applied by superfusion or by pressure ejection from
      micropipettes predominantly inhibited the intracellularly recorded fast
      inhibitory postsynaptic potential (fIPSP) and late hyperpolarizing potential
      (LHP) elicited by focal electrical stimulation of the DLSN. The decreases in LHP
      and fIPSP amplitude occurred at low concentrations of peptide, in the absence of
      appreciable changes in the passive-membrane properties of postsynaptic neurons,
      and outlasted the membrane hyperpolarizing effect produced by SS-14 at higher
      concentrations. The ability of SS-14 to modulate postsynaptic GABA receptor
      responses underlying the fIPSP and LHP were investigated by applying baclofen, a
      selective GABAB receptor agonist, and isoguvacine, a selective GABAA receptor
      agonist, by pressure ejection. Hyperpolarizing responses to GABAA and GABAB
      receptor stimulation were significantly decreased during superfusion of SS-14.
      Tetrodotoxin applied by superfusion blocked electrically evoked synaptic
      potentials but not the depressant effect of SS-14 on baclofen- or isoguvacine
      induced hyperpolarization. Facilitation of the fIPSP or LHP by SS-14 also
      occurred but less frequently and consistently than the depressant action.
      Excitatory postsynaptic potentials and membrane response to NMDA or quisqualate
      appeared unaltered by bath-applied SS-14. These findings suggest a novel
      postsynaptic action of SS-14 leading to depression of synaptic responses mediated
      by GABAA and GABAB receptors. Synaptically released SS-14 in the DLSN may
      participate in modulation of feedforward and/or feedback inhibitory mechanisms
      coordinating DLSN function in the septo-hippocampal system.

PMID- 1975767
TI  - Biphasic action of dextrorphan on penicillin induced bursting in rat hippocampal
      slice.
AB  - Effects of dextrorphan (DX), a metabolite of the over-the-counter antitussive,
      dextromethorphan, were investigated in rat hippocampal slices exposed to the
      epileptogenic agent penicillin. At 50 microM and 100 microM concentrations
      dextrorphan suppressed late components of the epileptiform CA1 field potential
      elicited by afferent electrical stimulation, and partially suppressed the
      intracellularly recorded paroxysmal depolarization shift. These effects were not
      due to non-specific changes in cell excitability, since resting cell membrane
      potential, input resistance, and the ability of cells to fire action potentials
      in response to direct depolarizing current were unaffected. The depressant effect
      of 100 microM dextrorphan was probably due to actions at the NMDA receptor, since
      pretreatment with the competitive NMDA antagonist D-APV prevented any further
      depressant effects of dextrorphan in this model. In contrast, at a 10 microM
      concentration DX enhanced the amplitude of evoked epileptiform field potentials
      and intracellularly recorded EPSPs. These findings support a role for dextrorphan
      and similar agents as anticonvulsants at high concentrations, but raise a caution
      regarding possible excitatory actions of dextrorphan at low concentrations.

PMID- 1975769
TI  - [New single point mutation at the initiation codon (ATG-AGG) identified in
      amplified genomic DNA of a Chinese with beta-thalassaemia].
AB  - A new single nucleotide change at nt 2 of exon 1 of the beta-globin gene was
      identified in a Chinese female patient with beta-thalassaemia. Dot blot
      hybridization of the amplified genomic DNA with oligonucleotide probes showed
      that she carried the four base deletions at the codons 41/42. Direct DNA
      sequencing on the amplified DNA revealed that she also carried a new mutation
      (ATG-AGG) at the initiation codon on the other beta-globin gene. This single
      nucleotide change abolishes a NcoI recognition site and hence it can be directly
      visualized after gel electrophoresis. Analyses of restriction fragment length
      polymorphisms showed that she also carried a rightward -3.7 kb (type I) deletion
      in her alpha-globin genes, and is in fact a alpha beta-thalassaemia genotype.

PMID- 1975768
TI  - In vivo evidence for an inhibitory glutamatergic control of serotonin release in
      the cat caudate nucleus: involvement of GABA neurons.
AB  - The local effect of L-glutamic acid (5 x 10(-5) M) on the release of
      [3H]serotonin continuously synthesized from [3H]tryptophan was examined in the
      caudate nucleus of 'encephale isole' unanaesthetized cats implanted with push
      pull cannula. L-Glutamic acid (5 x 10(-5) M) decreased [3H]serotonin release from
      nerve terminals of the dorsalis raphe-striatal serotonergic neurons. The effect
      was antagonized by 2-amino-6-trifluoromethoxybenzothiazole (PK 26124) (10(-6) M),
      an antagonist of glutamatergic transmission. This effect was mimicked by N
      methoxy-D-aspartic acid NMDA (5 x 10(-5) M) and prevented by DL-2-phosphono
      valeric acid (APV) (5 x 10(-6) M), indicating that L-glutamic acid decreased
      serotonin release via a N-methoxy-D-aspartate type receptor. The superfusion of
      serotonergic nerve terminals in the caudate nucleus with tetrodotoxin prevented
      the inhibitory L-glutamic acid-induced effect on serotonin release. Furthermore,
      L-glutamic acid-induced inhibition of [3H]serotonin release was antagonized by
      bicuculline (5 x 10(-5) M). These data suggest that the glutamatergic receptors
      involved were not located directly on serotonin nerve terminals. The inhibitory
      control exerted by L-glutamic acid on serotonergic transmission could involve
      gamma-aminobutyric acid interneurons. Since no reduction of spontaneous
      [3H]serotonin release was observed in the presence of bicuculline, GABAergic
      neurons appeared to exert a phasic influence on serotonin release. Indirect
      inhibitory presynaptic control on serotonin release mediated by corticostriatal
      glutamatergic fibers is discussed in light of previous findings.

PMID- 1975770
TI  - Changes in membrane lipids and amino acid transport in a nystatin-resistant
      Aspergillus niger.
AB  - A nystatin-resistant mutant of Aspergillus niger is described that has
      quantitative changes in phospholipid composition compared with the wild type. The
      proportion of linoleic acid in total phospholipids was elevated in the mutant
      from 38 to 56% and the proportion of oleic acid was lowered from 28 to 12%. Amino
      acid transport is also altered, the Vmax values for the uptake of leucine,
      lysine, and glutamic acid being generally higher in the mutant; for glutamic acid
      the increase was from 15 to 35 nmol.mg-1.min-1.

PMID- 1975771
TI  - The isotype potential of B cells present in BALB/c mice chronically infected with
      Mesocestoides corti.
AB  - Infection of BALB/c mice with Mesocestoides corti results in a chronic infection
      with a pronounced splenomegaly and hypergammaglobulinemia. A prominent feature of
      this infection is that the vast majority of serum immunoglobulin produced is
      restricted to IgG1 and IgM. As much as 30-fold increases in serum IgG1 levels
      have been noted. To ascertain whether, as a result of infection, the resident B
      cell pool is committed to IgG1, B cells from infected animals were tested for
      their ability to produce various isotypes after stimulation. In one series of
      experiments, B cells from normal and infected animals were used as donor cells in
      the splenic fragment assay. The results show that the frequency of 2,4
      dinitrophenyl-specific and phosphorylcholine-specific B cells remains unaltered
      in infected animals compared to controls. Importantly, the hapten-specific B cell
      clones induced were found to express multiple isotypes. These results demonstrate
      that the nonactivated B cell pool in spleens of infected mice is not committed to
      IgG1 and IgM production.

PMID- 1975772
TI  - Nonrandom migration of CD4+, CD8+, and gamma delta+T19+ lymphocyte subsets
      following in vivo stimulation with antigen.
AB  - We report here the results of experiments in which the migration of three T cell
      subsets (CD4+, CD8+, and gamma delta+T19+ cells) through antigen-stimulated lymph
      nodes and subcutaneous granulomas has been compared with that through normal skin
      and resting lymph nodes. The percentage of gamma delta+T19+ lymphocytes was
      halved and the percentage of CD8+ lymphocytes was doubled in lymph draining
      stimulated compared with control tissues, and all lymphocyte subsets except gamma
      delta+T19+ lymphocytes had higher hourly outputs in lymph draining antigen
      stimulated compared with control tissues. Antigen also resulted in a higher
      percentage of CD8+ lymphoblasts and a lower percentage of gamma delta+T19+
      lymphoblasts in efferent lymph draining antigen-stimulated lymph nodes. The data
      indicate that lymphocyte subsets leave the blood with differing efficiencies in
      different vascular beds and raise the possibility that antigen can influence the
      rate at which tissues extract individual T cell subsets from the blood.

PMID- 1975773
TI  - [Study of pulmonary T cell subsets and killer activity in lung cancer].
AB  - Studies were performed to determine natural killer (NK) activity (ability to lyse
      51Cr labeled K562 target cells) and T cell subsets (with OKT3, OKT4, or OKT8
      antigen detected by indirect immunofluorescence technique) both in
      bronchoalveolar lavage fluid (BALF) and peripheral blood of 40 lung cancer
      patients with different pathological type and 39 healthy controls. Our results
      showed that the percentage of total T cell (T3) and T suppressor cells in BALF
      were elevated both in the tumour involved and healthy lungs of the patients when
      compared with those of the normal controls. NK activity levels in BALF of the
      uninvolved lung and the controls were low. However, NK activity at tumour sites
      and the adjacent airways were significantly higher. There was no difference of NK
      activity in peripheral blood between lung cancer patients and the controls. The
      results demonstrated immune assays for BALF are very important parameters to
      investigate the changes of immune surveillance of the lung cancer patients. The
      higher NK activity and the reduced T4/T8 ratio in the lung with cancer may play
      important roles in local immunity.

PMID- 1975774
TI  - [Effect of monoamine neurotransmitters in the hypothalamus in a cortisol-induced
      rat model of yang-deficiency].
AB  - Eight monoamine neurotransmitters in hypothalamus of normal and cortisol-induced
      Yang-deficiency rats were measured with HPLC-ECD. These neurotransmitters
      included: (1) Noradrenaline (NA); (2) Adrenaline (A); (3) 3-methoxy-4
      hydroxyphenyl glycol (MHPG); (4) 3,4-dihydroxyphenylacetic acid (DOPAC); (5)
      Dopamine (DA); (6) 5-hydroxyindole-3-acetic acid (5-HIAA); (7) Homovanillic acid
      (HVA); and (8) Serotonin (5-HT). With the mobile phase of 10% methanol-0.15 M
      chloroacetic acid-sodium hydroxide buffer, the neurotransmitters might be well
      separated, the sensitivity was similar to that of gas chromatography-mass
      spectrogram with the lower limit of 0.1 ng, this assay was simple and might be
      accomplished with half an hour. The Yang-strengthening Chinese herbs Radix
      Aconiti Praeparata, Cortex, Cinamomi, Epimedium brevicorum and Herba Cistanchis
      were used in the study and the following were founded: (1) In the hypothalamus of
      cortisol-induced Yang-deficiency rat NA decreased and a increased when compared
      with that of the normal controls (both P less than 0.05). (2) After 4 weeks of
      administration of Yang-strengthening herbs, the NA and A of the Yang-deficiency
      rats returned to nearly normal and it suggested these herbs have the effect of
      "supporting the right and recovering the source"; DA markedly increased both in
      control rats and Yang-deficiency rats (P less than 0.05, P less than 0.001
      respectively); DOPAC obviously decreased both in control rats and Yang-deficiency
      rats (P less than 0.001); 5-HT and 5-HIAA increased in the control rats (both P
      less than 0.001) and HVA significantly decreased in Yang-deficiency rats. (3) The
      ratio of DA/DOPAC and 5-HT/5-HIAA markedly increased both in the control and Yang
      deficiency rats after using Yang-strengthening herbs (P less than 0.01-0.001) and
      it suggested Yang-strengthening herbs could inhibit the activity of monoamine
      oxidase in hypothalamus.

PMID- 1975775
TI  - DARPP-32 development in the caudate nucleus is independent of afferent input from
      the substantia nigra.
AB  - DARPP-32, a dopamine- and adenosine 3':5'-monophosphate regulated neuronal
      phosphoprotein, Mr 32 kDa, is a phenotypic marker of the medium-size spiny
      neurons of the mammalian caudate-putamen. In the present study, we examined the
      ontogeny of DARPP-32 protein and mRNA, and compared it to the ontogeny of
      tyrosine hydroxylase and synapsin I, a synaptic-vesicle phosphoprotein. In vivo,
      the amount of DARPP-32 protein per mg total protein increased throughout the
      first three postnatal weeks, and then declined to plateau at adult levels. The
      mRNA level closely paralleled the protein, except that its rise preceded that of
      the protein. Tyrosine hydroxylase levels rose throughout the first 4 postnatal
      weeks, and synapsin I levels rose steadily during the same period. Primary
      reaggregate cultures containing cells from the caudate-putamen expressed DARPP-32
      with a time course similar to that seen in vivo. The level of expression was not
      altered by coculturing with dopaminergic neurons from the rostral mesencephalic
      tegmentum. Thus, the postnatal increase in DARPP-32 levels in the caudate-putamen
      appears to be independent of transsynaptic or end-organ influences from the
      substantia nigra.

PMID- 1975776
TI  - The expression of excitatory amino acid binding sites during neuritogenesis in
      the developing rat cerebellum.
AB  - The present study has examined excitatory amino acid transmitter binding sites as
      measured autoradiographically in cryostat sections prepared from developing rat
      cerebella during the period of granule cell neuritogenesis. The external germinal
      layer (EGL) and molecular layer (ML), which during development contain granule
      cells at early stages of axon growth, contained only low levels of NMDA
      displaceable L-[3H]glutamate binding sites. Similarly, [3H]glycine binding to the
      NMDA receptor linked binding site was not enriched in the EGL. Radioligand
      binding to the NMDA receptor was always greater in the granular layer (GL) than
      in the ML. The developmental increases in NMDA-displaceable L-[3H]glutamate and
      in [3H]glycine binding to the GL were similar but NMDA displaceable L
      [3H]glutamate binding density increased before [3H]glycine binding sites. Glycine
      increased NMDA-displaceable L-[3H]glutamate binding only in the adult cerebellum.
      These results suggest that NMDA stimulation of neuritogenesis in granule cell
      cultures may reflect stimulation of dendritogenesis in the developing glomerulus
      rather than a stimulation of axon growth in the EGL. Also, NMDA receptors may be
      present in an immature form during cerebellar development and have different
      properties to the adult receptor. Binding sites for [3H]kainate and [3H]AMPA were
      present in both the GL and ML and increased during development. At all times the
      amount of binding sites for [3H]kainate were highest in the GL whereas those for
      [3H]alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate were highest in the ML.

PMID- 1975777
TI  - Control of NMDA receptor-mediated activity by GABAergic mechanisms in mature and
      developing rat neocortex.
AB  - The effects of diazepam and low concentrations of bicuculline methiodide (BMI) on
      the expression of long-latency N-methyl-D-aspartate (NMDA) receptor-mediated
      activity was studied in supragranular layers of juvenile (14-18 days old) and
      adult rat (greater than or equal to 28 days) primary somatosensory cortex. In
      juvenile slices, orthodromic stimulation of layer VI/white matter evoked a long
      lasting oscillatory field potential response which could be blocked by the NMDA
      receptor antagonist D(-)-2-amino-5-phosphonovaleric acid (D-APV) and by diazepam.
      Similar D-APV-sensitive responses could be observed in adult slices when the
      GABAergic system was slightly suppressed by adding low doses of BMI to the
      bathing solution. Our findings indicate that a small decrease in the efficacy of
      the inhibitory system, whether caused by developmental events or by processes
      that modulate inhibitory electrogenesis, can lead to NMDA receptor-mediated
      synchronized afterdischarges, which might play an important role in the
      functional maturation of the neocortex and in susceptibility to epileptogenesis.

PMID- 1975778
TI  - Lack of association of T cell receptor beta-chain constant region polymorphism
      with insulin-dependent diabetes mellitus in Finland.
AB  - Allelic polymorphism in the T cell receptor constant beta-chain gene region has
      been reported to be associated with autoimmune diseases, including insulin
      dependent diabetes mellitus (IDDM). The present analysis of 164 children and
      adolescents with IDDM and 193 controls for BqlII polymorphism using a TcR-C beta
      cDNA probe revealed two allelic restriction fragments with sizes of 10.5 kb (U)
      and 9.6 kb (L). No particular association was observed between the RFLP genotypes
      and IDDM (UU 27% versus 31%; UL 53% versus 52%; and LL 20% versus 17%, in
      diabetic subjects and controls, respectively), nor were any differences found
      between patients with various HLA risk antigens. The frequency of heterozygotes
      was 52% in 63 DR3-positive diabetic subjects and 53% in 73 DR3-negative ones. The
      results do not support any involvement of the TcR constant region genes in
      susceptibility to IDDM.

PMID- 1975779
TI  - Expression of LFA-1 by a lymphoblastoid cell line from a patient with monosomy
      21: effects on intercellular adhesion.
AB  - Monosomy 21 (M21) is a rare aneuploid condition which in certain cases leads to
      reduced levels of chromosome 21 gene products. We have prepared an Epstein-Barr
      virus lymphoblastoid cell-line (LCL) from patient with M21 who has immunological
      abnormalities, and analysed the expression of lymphocyte function-associated
      antigen-1 (LFA-1). This heterodimeric leucocyte integrin consists of CD11a
      (alpha) subunits non-covalently associated with CD18 (beta) subunits coded,
      respectively, by genes on chromosomes 16 and 21. To determine whether monosomy 21
      results in decreased expression of LFA-1, monoclonal antibodies were used to
      compare the expression of CD11a and CD18 on the M21 LCL with LCL from trisomy 21
      (Down's syndrome, T21), normal controls and a possible case of leucocyte adhesion
      deficiency. In addition, phorbol-ester-induced homotypic adhesion, an LFA-1
      mediated effect, was compared in these LCLs. The results are consistent with a
      gene dosage mediated reduction of LFA-1 expression by the M21 LCL.

PMID- 1975780
TI  - Acute and long-term haemodynamic and neurohumoral response to nisoldipine vs
      captopril in patients with heart failure: a randomized double-blind study.
AB  - To study the haemodynamic and neurohumoral effects of nisoldipine (2 X 10 mg) vs
      captopril (3 X 25 mg), 24 patients with heart failure (New York Heart Association
      class II and III) due to coronary artery disease were treated in a randomized
      double-blind trial over 3 months. Both drugs were well tolerated. Clinical status
      was similarly improved in both groups, nisoldipine exerted an additional
      antiischaemic effect. Nisoldipine lowered the mean arterial pressure and
      capillary wedge pressure acutely and also after long-term treatment. The increase
      in cardiac index and stroke volume index, however, which was pronounced after
      acute administration, was no longer present after 3 months of therapy at rest and
      was abolished during exercise. Norepinephrine plasma concentration increased
      after the first dose, plasma renin activity did not change, and aldosterone
      plasma concentration showed a small insignificant decrease. Urine concentrations
      of norepinephrine and vasopressin were slightly elevated after the 3-month
      therapy. After captopril, mean arterial pressure and pulmonary capillary wedge
      pressure decreased acutely and at follow up. Cardiac index and stroke volume
      index increased significantly only during exercise at follow-up. Plasma renin
      activity was significantly elevated and aldosterone plasma concentration only
      slightly lowered. In contrast to what was seen with nisoldipine, plasma
      norepinephrine concentration and urine catecholamine and vasopressin
      concentrations remained unchanged. In conclusion, the pronounced haemodynamic
      effects seen after the first dose of nisoldipine are mostly abolished after long
      term treatment, probably due to neurohumoral counterregulation. The haemodynamic
      response to captopril is complete only after long-term treatment, without
      evidence of activation of the neurohumoral systems.

PMID- 1975781
TI  - Effects of alpha 1- and alpha 2-adrenoceptor antagonists on venous tone in
      conscious rats.
AB  - The dose-response effects of hexamethonium, prazosin and rauwolscine - a
      ganglionic blocker, alpha 1- and alpha 2-adrenoceptor antagonists, respectively -
      on mean arterial pressure (MAP) and mean circulatory filling pressure (MCFP), an
      index of body venous tone, were examined in conscious and unrestrained rats.
      Prazosin and rauwolscine were also administered to rats after venous tone was
      elevated by drug-induced hypotension via the infusion of the vasodilator drug
      hydralazine. The effects of these drugs were compared with those of the vehicle,
      acidified glucose solution, administered to control rats. In intact rats, i.v.
      infusions of prazosin and rauwolscine dose dependently decreased MAP; the highest
      dose of rauwolscine, but not prazosin slightly reduced MCFP. The i.v. infusion of
      hexamethonium reduced MAP and caused a marked dose-dependent decrease in MCFP.
      After venous tone was raised by hydralazine, both prazosin and rauwolscine dose
      dependently decreased MCFP. The decrease in MCFP caused by rauwolscine was
      significantly greater than that caused by prazosin. Our results show that in the
      basal condition, the capacitance vessels are somewhat resistant to the effects of
      alpha-adrenoceptor antagonists in contrast to the effects of ganglionic blockers.
      After venous tone was raised by reflex mechanisms, both alpha-adrenoceptor
      antagonists were effective in lowering venous tone, however, the effect of alpha
      2-adrenoceptor antagonist is significantly greater than that of alpha 1
      adrenoceptor antagonist.

PMID- 1975782
TI  - Striatal and nucleus accumbens D1/D2 dopamine receptors in neuroleptic catalepsy.
AB  - Haloperidol (2.5-10 micrograms) injected bilaterally into the ventro-rostral
      striatum or into the nucleus accumbens induced dose-dependent catalepsy whereas
      its injection into the dorso-rostral striatum (2.5 micrograms) was ineffective.
      Similarly, the specific antagonist of D1 receptors, SCH 23390 (1-5 micrograms),
      injected into the ventro-rostral striatum or nucleus accumbens, as well as the
      specific antagonist of D2 receptors, sulpiride, injected into the ventro-rostral
      striatum (0.02-15 micrograms) or nucleus accumbens (1-15 micrograms), induced a
      dose-dependent catalepsy. Both drugs (SCH 23390 2 micrograms, sulpiride 0.5
      micrograms) were ineffective when injected into the dorso-rostral striatum. Doses
      of sulpiride about 100 times lower than those injected into the nucleus accumbens
      were sufficient to evoke an equipotent catalepsy when injected into the ventro
      rostral striatum. However, similar doses of haloperidol and SCH 23390, injected
      into the ventro-rostral striatum and nucleus accumbens, evoked a similar
      catalepsy. It is concluded that (1) the catalepsy induced by systemic
      administration of haloperidol seems to result from the action of this drug on
      both the ventro-rostral striatum and the nucleus accumbens, (2) both D1 and D2
      dopamine receptors in the ventro-rostral striatum are involved in the
      cataleptogenic action of neuroleptics, and (3) in the nucleus accumbens, only D1
      dopamine receptors seem to play an important role in this phenomenon.

PMID- 1975783
TI  - P2 purinoceptor agonists stimulate somatostatin secretion from dog pancreas.
AB  - The effects of ATP and ADP structural analogues (2-methylthio ATP; alpha,beta
      methylene ADP) on somatostatin secretion were tested in dogs. Insulin and
      glucagon secretion was also evaluated. Our experiments were performed in vivo and
      in vitro. In vivo, 2-methylthio ATP was infused directly into the
      pancreaticoduodenal artery of anesthetized dogs and blood was sampled from the
      pancreaticoduodenal vein. This ATP analogue (approximately 15 microM) immediately
      induced stimulation of both somatostatin and insulin secretion, which was
      accompanied by a slight reduction of glycemia. A delayed increase in glucagon
      output was observed. In vitro, using the isolated perfused dog pancreas uncinate
      process, alpha,beta-methylene ADP, a stable ADP analogue (16.5 microM), was
      infused in the presence of a substimulating glucose concentration (4.2 mM). Under
      these conditions, alpha,beta-methylene ADP immediately induced the stimulation of
      somatostatin secretion without affecting basal insulin and glucagon secretion. In
      conclusion our results suggest the presence of P2 purinoceptors on pancreatic
      somatostatin secreting cells.

PMID- 1975784
TI  - Effects of dopamine D1 and D2 agonists and antagonists injected into the nucleus
      accumbens and globus pallidus on jaw movements of rats.
AB  - The effects of bilateral injections of selective D1 and D2 agonists and
      antagonists into the anteromedial part of the nucleus accumbens and the globus
      pallidus on apomorphine-induced jaw movements were studied in ketamine
      anaesthetized rats after C1 spinal transection. Both SCH 23390 (0.1 and 1
      micrograms) and 1-sulpiride (5 and 25 ng) injected into the nucleus accumbens
      suppressed the display of jaw movements after apomorphine (0.5 mg/kg i.v.).
      Injection of 1-sulpiride (5 and 25 ng) into the globus pallidus also blocked the
      effect of apomorphine, whereas SCH 23390 (1 microgram) injected into the same
      site was ineffective in this respect. Simultaneous application of the selective
      D1 and D2 agonists, SKF (1 or 5 micrograms) + quinpirole (10 micrograms), into
      the nucleus accumbens strongly potentiated the effect induced by local
      administration of each drug alone; a comparable, but smaller, effect was seen
      after simultaneous injections of these agents into the globus pallidus. These
      results show that dopaminergic mechanisms within the nucleus accumbens are
      involved in apomorphine-induced jaw movements, and that the expression of these
      movements requires concurrent activation of D1 and D2 receptors.

PMID- 1975785
TI  - Regulation of beta-adrenoceptors in the guinea pig left ventricle and skeletal
      muscle following chronic agonist treatment.
AB  - Pretreatment of guinea pigs with adrenaline, isoprenaline or terbutaline for 7
      days significantly reduced the Bmax for the radioligand [125I]cyanopindolol
      (ICYP) in the gastrocnemius muscle (beta 2-adrenoceptors). Pretreatment of guinea
      pigs with terbutaline reduced the responsiveness of gastrocnemius muscle slices
      adenylate cyclase to isoprenaline (10(-4) M). In the left ventricle
      (predominantly beta 1-adrenoceptors) pretreatment of guinea pigs with
      isoprenaline or adrenaline for 7 days did not alter the Bmax for ICYP. The
      responsiveness of adenylate cyclase to isoprenaline (10(-4) M) in left ventricle
      slices was significantly reduced following isoprenaline pretreatment of the
      guinea pigs. Thus desensitisation of beta-adrenoceptors in left ventricle and
      skeletal muscle developed following chronic agonist pretreatment. Reduction of
      beta 2-adrenoceptors in the skeletal muscle could be responsible for the
      desensitisation of adenylate cyclase. In the left ventricle the receptors were
      resistant to agonist induced down-regulation. It is proposed that other
      mechanisms which are tissue- and species-specific independent of the receptor
      subtype can be responsible for agonist-induced desensitisation in the left
      ventricle of the guinea pig in vivo.

PMID- 1975786
TI  - EDRF release is a common pathway in the activation of guanylate cyclase by
      receptor agonists and calcium ionophores.

PMID- 1975787
TI  - Expression of neuropeptide Y immunoreactivity in the rat nucleus accumbens is
      under the influence of the dopaminergic mesencephalic pathway.
AB  - The density of neuropeptide Y (NPY) immunostained neurons examined in the rat
      nucleus accumbens (NAcc) was shown to be constant across the anteroposterior
      extent of the nucleus and did not present any right-left hemispheric difference.
      Selective unilateral 6-hydroxydopamine (6-OHDA) lesion of the nigral dopaminergic
      neurons induced, 15 to 21 days later, a bilateral decrease in the NPY neuron
      density which was, interestingly, more marked in the contralateral than in the
      ipsilateral NAcc. Dopamine depletion induced by alpha-methylparatyrosine
      treatment elicited a decrease in NPY neuronal density similar in amplitude to
      that induced by the 6-OHDA lesion in the ipsilateral NAcc suggesting that similar
      mechanisms underly both NPY responses. In both experimental conditions, changes
      in NPY immunostaining were quite homogeneous in the two antero-posterior NAcc
      portions arbitrarily considered. Apomorphine treatment in animals with 6-OHDA
      injury completely reversed the ipsilateral lesion effect in the anterior part of
      the NAcc but only partially the contralateral one. In contrast, no significant
      effect of apomorphine was observed in either side of the NAcc posterior portion.
      This data suggests the involvement of at least 2 components in the NPY neuron
      responses to the lesion. The component reversed by apomorphine treatment was
      presumed to be directly linked to the DA depletion, while the second component
      not antagonized by apomorphine was considered independent on DA transmission.
      These data therefore provide morphological evidence for the occurrence of complex
      functional interactions between dopaminergic afferents and NPY-containing neurons
      within the NAcc.

PMID- 1975788
TI  - Seizure suppression in kindling epilepsy by intrahippocampal locus coeruleus
      grafts: evidence for an alpha-2-adrenoreceptor mediated mechanism.
AB  - Intrahippocampal cell suspension grafts, prepared from the locus coeruleus region
      of rat fetuses, have previously been shown to retard seizure development in rats
      made hypersensitive to hippocampal kindling by a lesion of the forebrain
      noradrenergic system. The objective of the present study was to provide evidence
      that the seizure-suppressant effect elicited by the grafts is mediated via
      noradrenergic mechanisms. Two groups of rats received 6-hydroxydopamine in the
      lateral ventricle and then bilateral intrahippocampal locus coeruleus grafts.
      After 3 months, the grafted animals and a group of normal rats were subjected to
      hippocampal kindling. One group of grafted animals and the normal rats were
      injected intraperitoneally with the alpha-2 adrenergic receptor blocker idazoxan
      before each kindling stimulation. The other grafted rats received vehicle
      injections. The development of seizures was significantly faster in the grafted
      and normal rats that had been given idazoxan than in the grafted rats that had
      not been subjected to alpha-2 receptor blockade. Our data suggest that the
      seizure-suppressant action exerted by grafts of fetal locus coeruleus in
      hippocampal kindling is mediated via noradrenergic mechanisms, most likely via
      activation of postsynaptic alpha-2 adrenoreceptors.

PMID- 1975789
TI  - Inhibition of alpha-aminoadipate-semialdehyde dehydrogenase from Trichosporon
      adeninovorans by lysine and lysine analogues.
AB  - The alpha-aminoadipate-semialdehyde dehydrogenase (EC 1.2.1.31) of Trichosporon
      adeninovorans, an enzyme of lysine biosynthesis, was partially purified, some
      properties of the enzyme were studied and a novel regulatory pattern was found.
      The Km values of the enzyme were estimated to be 0.78 mM for alpha-aminoadipate,
      1.0 mM for ATP, 0.23 mM for NADPH and 0.77 mM for MgCl2. It is demonstrated that
      the enzyme can be regulated by lysine and lysine analogues. L-Lysine (Ki of 0.09
      mM), S-(beta-aminoethyl)-L-cysteine (Ki of 0.007 mM) and delta-hydroxylysine (Ki
      of 1.65 mM) inhibited the enzyme activity. The inhibition was competitive with
      respect to alpha-aminoadipate and non-competitive with respect to both ATP and
      NADPH.

PMID- 1975790
TI  - Genetic and molecular analysis of vgU and vgW: two dominant vg alleles associated
      with gene fusions in Drosophila.
AB  - In the absence of a vg+ gene, extensive cell death occurs in third instar
      imaginal discs, which results in a complete loss of adult wing margin structures.
      Essentially all molecularly characterized vg alleles are associated with
      deletions or insertions of DNA into the vg locus. These alterations reduce or
      eliminate a 3.8-kb vg-specific transcript, resulting in recessive loss of
      function alleles. We report here the analysis of two dominant vg alleles which
      have been identified (vgU and vgW). The vgU allele is associated with a
      chromosomal inversion which splits the vg locus, resulting in a gene fusion
      between vg and the mastermind (mam) neurogenic locus. Reversion analysis of vgU
      indicates that sequences from the mam locus are required for vgU dominance. The
      vgW allele is also the result of a chromosomal inversion, in this case resulting
      in a gene fusion between vg and the homeobox-containing invected (inv) gene. It
      is also associated with novel dominant homeotic transformations. Revertant
      analysis indicates that sequences from inv are required for the dominant wing and
      dominant homeotic effects of vgW. The vg dominance does not appear to be mediated
      through a reduction of vg expression or a novel fusion transcript in either vgU
      or vgW. The results are consistent with a model in which inappropriate expression
      of inv causes the dominant homeotic effects seen in vgW.

PMID- 1975792
TI  - A simple method for estimating average number of nucleotide substitutions within
      and between populations from restriction data.
AB  - A simple method is proposed for estimating the average number of nucleotide
      substitutions per site within and between populations for the case where a large
      number of individuals are examined for many restriction enzymes. This method
      gives essentially the same results as those obtained by Nei and Li's method but
      saves a large amount of computer time. The variances of the quantities estimated
      can be obtained by the jackknife method, and these variances are very similar to
      those obtained by Nei and Jin's more sophisticated method. A similar method can
      also be applied to DNA sequence data.

PMID- 1975793
TI  - [Ultrastructural changes in the C-cells of the thyroid gland of albino rats after
      experimental administration of cadmium].

PMID- 1975791
TI  - A genetic linkage map of mouse chromosome 10: localization of eighteen molecular
      markers using a single interspecific backcross.
AB  - Interspecific mouse backcross analysis was used to generate a molecular genetic
      linkage map of mouse chromosome 10. The map locations of the Act-2, Ahi-1, Bcr,
      Braf, Cdc-2a, Col6a-1, Col6a-2, Cos-1, Esr, Fyn, Gli, Ifg, Igf-1, Myb, Pah,
      pgcha, Ros-1 and S100b loci were determined. These loci extend over 80% of the
      genetic length of the chromosome, providing molecular access to many regions of
      chromosome 10 for the first time. The locations of the genes mapped in this study
      extend the known regions of synteny between mouse chromosome 10 and human
      chromosomes 6, 10, 12 and 21, and reveal a novel homology segment between mouse
      chromosome 10 and human chromosome 22. Several loci may lie close to, or
      correspond to, known mutations. Preferential transmission of Mus spretus-derived
      alleles was observed for loci mapping to the central region of mouse chromosome
      10.

PMID- 1975794
TI  - Somatostatin and vasoactive intestinal peptide reduce interferon gamma production
      by human peripheral blood mononuclear cells.
AB  - There is increasing evidence that neuropeptide modulation of the immune response
      is an important physiological phenomenon which involves the interaction of
      peptidergic neuromodulators with specific neuropeptide receptors on the plasma
      membrane of immune effector cells. Many studies have examined the effect of
      neuropeptides on mitogen-induced lymphocyte proliferation and immunoglobulin
      synthesis but very little is known about specific lymphokine production. In this
      study, we describe the effect of somatostatin (SOM) and vasoactive intestinal
      peptide (VIP) on interferon gamma (IFN-gamma) production by normal human
      peripheral blood mononuclear cells (PBMC) stimulated in vitro with polyclonal T
      cell activator staphylococcal enterotoxin A (SEA). Our findings provide
      experimental evidence that both SOM and VIP reduce the IFN-gamma production by
      SEA-stimulated PBMC. This reduction was time- (with maximal effect at 72 h) and
      dose-dependent (at doses as low as 10(-11) M with maximal effect at
      concentrations between 10(-9) and 10(-8) M of neuropeptides). This effect was
      absent in resting PBMC. The meaning of inhibitory effect of VIP and SOM on IFN
      gamma production and its role in immune response in vivo are discussed.

PMID- 1975795
TI  - Importance of ICAM-1 for accessory cell function of monocytic cells.
AB  - We investigated to what extent the adherence molecule ICAM-1 is important for the
      accessory cell function of cells of the monocyte lineage. A monoclonal antibody
      to ICAM-1, 7F7, inhibited the accessory cell function of human peripheral blood
      monocytes cultured in the presence of serum for 1-3 days. Monocyte, cultured for
      4-7 days still expressed ICAM-1 but their accessory cell function was no longer
      inhibited by the antibody 7F7. Dendritiform accessory cells, obtained by culture
      of peripheral blood monocytes in serum free medium for 1-2 days also expressed
      ICAM-1 and their capacity to stimulate T-cells was also abrogated by antibody
      7F7. These findings suggest that ICAM-1 on the surface of accessory cells of a
      certain differentiation stage seems to contribute to the capacity of these cells
      to stimulate T-cells but, that in some situations accessory cell function can
      occur normally without requiring ICAM-1 dependent cell to cell interactions.

PMID- 1975796
TI  - Dominant reduced responsiveness controlled by H-2(Kb)Ab. A new pattern evoked by
      Thy-1 antigen and F liver antigen.
AB  - In the most frequently used panel of H-2 recombinant strains, B10.A, B10.A(4R),
      B10.A(5R), and B10, inhibition of the immune response has hitherto mapped to H
      2E. Inhibition of the responses to Thy-1 antigen and to F liver protein, as
      described here, maps in a novel pattern to H-2KbAb, and presumably to H-2Ab.
      Enhancement of the adoptively transferred anti-Thy-1 response by treatment with
      CD8-specific antibody suggests, very provisionally, that T cells with suppressive
      activity mediate the inhibition. The evolution of this new pattern, and of
      dominant reduced responsiveness in general, is discussed and its relevance to
      immunological diseases assessed. An enzyme-linked immunosorbent assay (ELISA) for
      F-specific antibodies is introduced.

PMID- 1975797
TI  - The X boxes from promoters of HLA class II B genes at different loci do not
      complete for nuclear protein-specific binding.
AB  - Expression of HLA class II genes is coordinately regulated by cis-acting elements
      present in their promoter regions immediately upstream from the 5' end of their
      transcription start sites. Trans-acting factors from the nuclear proteins of the
      cell are able to positively or negatively regulate transcription of these genes
      by binding to highly conserved sequences, called boxes. After cloning the
      promoter regions of all the transcribed class II B genes present in the cell line
      Priess, we were able to identify certain protein-box complexes and to determine
      the affinity of these proteins for their respective boxes by comparing promoter
      boxes of each gene to those of the other genes. Different nuclear proteins seemed
      to bind to the X boxes of the different class II B genes tested. In the case of
      the Y box-protein complexes, the various Y boxes competed with similar
      affinities. The protein(s) which specifically bound to the DRB1-CCAAT box also
      bound to DPB1-CCAAT box, but completely failed to bind the homologous box from
      DQB1. Further, CCAAT box-specific protein(s) did not bind to the Y box of the
      same gene, excluding the possibility that these proteins just recognize the
      reverse CCAAT box (ATTGG) present within Y.

PMID- 1975798
TI  - Duplication of Tcra-V gene segments in the rat.

PMID- 1975799
TI  - Analysis of the C4 genes in baleen whales using a human cDNA probe.
AB  - We have used a human C4 cDNA probe to investigate the complement component C4
      gene in four members of the family Balaenopteridae: fin whale (Balaenoptera
      physalus), sei whale (B. borealis), minke whale (B. acutorostrata), and bryde's
      whale (B. edeni). Restriction mapping of genomic DNA from the first three species
      suggests the presence of only one locus in these species, and also shows that the
      C4 genes in the three species are very similar. We have used 14 restriction
      endonucleases to investigate the restriction fragment length polymorphism (RFLP)
      of fin whales, 13 enzymes for sei whales, and 8 enzymes for the minke whale. No
      polymorphism was seen in DNA from the five minke whale samples, but Rsa I and Taq
      I restriction enzymes gave polymorphism in fin and sei whales whereas Hind III
      and Msp I restriction enzymes showed polymorphism in sei whales only. Only one
      bryde's whale sample was available for investigation. The study of DNA available
      from mother-fetus pairs from the two polymorphic species demonstrated a simple,
      two-allele transmission of RFLP alleles.

PMID- 1975800
TI  - HLA-DQ RFLP variants of five HLA-DQw2-bearing major histocompatibility complex
      extended haplotypes.
AB  - We have analyzed genomic DNA in a large number of independent examples of five
      HLA-DQw2-bearing extended haplotypes for their associated subtypes by restriction
      fragment length polymorphism (RFLP) using DRB, DQA, and DQB probes after Taq I
      and Pst I digestion and Southern blotting. In addition to three previously
      described HLA-DQw2 subtypes, DQw2a, DQw2b, and DQw2c, we observed a fourth
      subtype, HLA-DQw2d, characterized by 5.8 kilobase (kb) DRB/Taq I, 2.4, 2.3, and
      1.8 kb DQB/Taq I, and 8.0 and 2.3 kb DQA/Pst I fragments. All 22 independent
      examples of the extended haplotype [HLA-B8, SC01, DR3] carried DQw2a and all 11
      independent examples of [HLA-B18, F1C30, DR3] carried DQw2b. In addition, all
      independent examples (21 and 4, respectively) of two DR7-carrying extended
      haplotypes, [HLA-B44, FC31, DR7] and [HLA-Bw47, FC91,0,DR7], carried DQw2c and
      all independent examples of [HLA-Bw57, SC61, DR7] carried DQw2d. Our results show
      that the DNA in the DR/DQ region of extended haplotypes is relatively fixed and
      that different DQw2 subtypes characterize different DQw2-bearing extended
      haplotypes.

PMID- 1975802
TI  - Characterization & larvicidal activity of indigenous isolates of Bacillus
      sphaericus from natural breeding habitats.
AB  - Soil, water and moribund/or dead mosquito larval samples collected from various
      mosquito breeding habitats of Pondicherry and Tamil Nadu were screened for the
      presence of mosquito pathogenic B. sphaericus isolates. From 1892 samples 21
      isolates were obtained. All these isolates fell under 3 serogroups viz., H5a5b,
      H6 and H45, the latter two serotypes not reported hitherto as toxic to mosquito
      larvae and three phage-groups namely, phage group 2, phage group 3 and an unknown
      one. Twelve of the isolates were highly toxic and superior to the standard
      strains 1593, 2297 and 2362 supplied by Pasteur Institute, Paris when tested
      against Culex quinquefasciatus larvae. Out of these 12 strains 11 belonged to the
      serotype H5a5b and the phage-group 3 and 1 belonged to the serotype H45 and an
      unknown phage group.

PMID- 1975803
TI  - Endurance to starvation by the immatures of Toxorhynchites splendens.
AB  - Studies on the endurance to starvation by the immatures of T. splendens showed
      that the III instar larvae survived longer than the I and II instar larvae. The
      IV instar larvae even in the absence of food pupated and emerged into adults. The
      irregular supply of food did not affect the perpetuation of the predator in the
      habitat.

PMID- 1975801
TI  - Unique sequences for two HLA-DRB1 genes expressed on distinct DRw6 haplotypes.
AB  - We have used restriction fragment length polymorphism (RFLP) analysis and DNA
      sequencing to characterize two distinct DRB1 alleles expressed on DRw52 and DQw7
      associated haplotypes but not readily defined by conventional DR serology. These
      two haplotypes, designated HLA-D "HAG" and "PEV", react variably with DRw13(w6),
      DRw14(w6), and the more broad DR"3 + 6" antisera. Analysis of RFLP revealed that
      HLA-D "HAG" and "PEV" are associated with different DRw52 variants, and that
      "HAG" is indistinguishable from DRw18(3) haplotypes. Sequencing of the "HAG" and
      "PEV" DRB1 genes showed each to represent novel alleles. Nevertheless, these
      sequences show similarities with the other alleles of the DR5,w6, and w8 family.
      "HAG" (DRB1*1303) appears to have arisen either from two recombinational events
      involving at least three DRB1 sequences (DRB1*1101, DRB1*0803, DRB1*0401) or from
      a single recombinational event together with multiple point mutational events.
      "PEV" appears to represent a DRB1*1301-1302/DRB1*1101 recombinant allele, with
      recombination having occurred in the region of bases 175-198. The results of this
      study suggest that the DRw52 family of haplotypes is derived from a relatively
      restricted number of ancestral sequences, with diversity among DRB1 alleles
      within this family arising through gene conversion or recombination events.

PMID- 1975804
TI  - Antibody to HTLV-I in indigenous inhabitants of the Andes and Amazon regions in
      Colombia.
AB  - To explore the HTLV-I-carrying groups among the indigenous inhabitants in South
      America, a sero-epidemiological study on HTLV-I focusing on hinterland villages
      isolated from others in the Andes and Amazon regions was conducted. Five (2.9%)
      out of 171 subjects showed positive for HTLV-I antibody in the gelatin particle
      agglutination (PA) test. Two out of 5 positives with high antibody titer (greater
      than or equal to x 1024) in the PA test also showed a positive immunofluorescence
      (IF) test and anti-HTLV-I-specific protein products, p19, p24, p28, gp46, and p53
      in sera by the Western blotting (WB) test. One of three negatives in the IF test
      showed positive antibodies to p19 and p24 by the WB test. Finally, two were
      confirmed as HTLV-I carriers and one was suspected of being a carrier. All three
      are Paez Indians from the central Andes; 53- and 34-year-old women and a 35-year
      old man. The results show that HTLV-I carriers exist among isolated indigenous
      people in South America.

PMID- 1975805
TI  - Specialized localization of P-glycoprotein recognized by MRK 16 monoclonal
      antibody in endothelial cells of the brain and the spinal cord.
AB  - This communication describes the cellular and ultrastructural localization in the
      central nervous system of P-glycoprotein (P-GP) recognized by a murine monoclonal
      antibody, MRK 16. At the ultrastructural level P-GP was strictly confined to the
      luminal surface of the endothelial cells which comprise the capillary vessels of
      the brain and the spinal cord. No P-GP was found in the endothelial cells of
      other organs. Our findings may be useful as a means to define the blood-brain
      barrier, and they imply that the blood-brain barrier is anatomically
      characterized by the presence of intercellular tight junctions between continuous
      nonfenestrated endothelial cells.

PMID- 1975806
TI  - Modulation by indomethacin or prostaglandin E2 of the incidence of
      diethylnitrosamine-induced gamma-glutamyltranspeptidase-positive foci in rat
      liver.
AB  - We investigated the effect of a pretreatment with indomethacin (IMC, ip 3.6 mg/kg
      body weight (bw)) or dimethylprostaglandin E2 (PGE2, ip 10 micrograms/kg bw) on
      the incidence and development of gamma-glutamyltranspeptidase (GGT)-positive foci
      of altered hepatocytes, scored 8 or 14 weeks after ip injection of
      diethylnitrosamine (DENA, 50 mg/kg bw) to rats submitted to two-thirds
      hepatectomy (PH) or sham operation (Sh). IMC reduced by about 4 times the
      incidence of DENA-induced GGT-positive foci per cm3 of liver tissue in sham
      operated as well as in two-thirds hepatectomized rats, compared to the respective
      unpretreated controls. In contrast, PGE2 pretreatment increased the incidence of
      DENA-induced foci in both groups, this effect, in terms of absolute numbers of
      foci, being additive to that of PH alone. IMC pretreatment resulted in foci with
      lower average size in the Sh but not in the PH animals, whereas with PGE2
      pretreatment the mean volume of the foci was increased in the two groups of rats.
      At the dose used, IMC did not modify the proliferative response of hepatocytes to
      PH, and PGE2 did not stimulate proliferation in the sham-operated animals.
      Altogether, these results indicate that: 1, the incidence of DENA-induced foci
      can be negatively modulated by interfering with the prostaglandins pathway
      through a mechanism that does not involve an action either on proliferative
      activity or on any other process that would be specific to the post-hepatectomy
      regenerative state; 2, positive modulation of the incidence of DENA-induced foci
      does not necessarily require stimulation of proliferation.

PMID- 1975807
TI  - Proton release from flavoprotein D-amino acid oxidase on complexation with the
      zwitterionic ligand, trigonelline.
AB  - Trigonelline, i.e., N-methylnicotinate, which has a zwitterionic structure
      similar to a substrate D-amino acid, is a useful active site probe for D-amino
      acid oxidase (DAO). The affinity of trigonelline for DAO in the deprotonated
      state at the enzyme bound FAD 3-imino group is higher than in the neutral state,
      contrary to in the case of benzoate, which is a competitive inhibitor and is in a
      monoanionic form. The time course of the absorbance change was monitored for the
      binding of DAO with trigonelline by means of a stopped-flow technique. The
      reaction, on monitoring at 507 nm, was found to be biphasic at pH 8.3, with fast
      and slow phases. The dissociation of the 3-imino proton of the enzyme bound FAD
      was observed in the same time course as the slow phase. These results suggest
      that the positive charge of trigonelline exists near the 3-imino group of the
      enzyme bound FAD and interacts repulsively with the proton of the 3-imino group.
      The absorption spectra of the DAO-trigonelline complex at various pHs also
      support this hypothesis. In the catalysis of DAO, a similar mechanism may be
      involved, that is, the positive charge of a D-amino acid may interact repulsively
      with the 3-imino proton of the enzyme bound FAD, and this interaction may be
      important for the catalysis.

PMID- 1975808
TI  - Site-directed mutagenesis of rat liver S-adenosylhomocysteinase. Effect of
      conversion of aspartic acid 244 to glutamic acid on coenzyme binding.
AB  - Aspartic acid 244 that occurs at the putative NAD(+)-binding site of rat liver S
      adenosylhomocysteinase was replaced by glutamic acid by oligonucleotide-directed
      mutagenesis. The mutant enzyme was purified to homogeneity as judged by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis. Gel permeation chromatography
      showed that the purified mutant enzyme was a tetramer as is the wild-type enzyme.
      In contrast to the wild-type enzyme, which possesses 1 mol of tightly bound NAD+
      per mol of enzyme subunit, the mutant enzyme had only 0.05 mol of NAD+ but
      contained about 0.6 mol each of NADH and adenine per mol of subunit. The mutant
      enzyme, after removal of the bound compounds by acid-ammonium sulfate treatment,
      exhibited S-adenosylhomocysteinase activity when assayed in the presence of NAD+.
      From the appearance of activity as a function of NAD+ concentration, the enzyme
      was shown to bind NAD+ with a Kd of 23.0 microM at 25 degrees C, a value greater
      than 280-fold greater than that of the wild-type enzyme. In the presence of a
      saturating concentration of NAD+, the mutant enzyme showed apparent Km values for
      substrates similar to those of the wild-type enzyme. Moderate decreases of 8- and
      15-fold were observed in Vmax values for the synthetic and hydrolytic directions,
      respectively. These results indicate the importance of Asp-244 in binding NAD+,
      and are consistent with the idea that the region of S-adenosylhomocysteinase from
      residues 213 to 244 is part of the NAD+ binding site. This region has structural
      features characteristic of the dinucleotide-binding domains of NAD(+)- and FAD
      binding proteins (Ogawa, H., Gomi, T., Mueckler, M. M., Fujioka, M., Backlund,
      P.S., Jr., Aksamit, R.R., Unson, C.G., and Cantoni, G.L. (1987) Proc. Natl. Acad.
      Sci. U.S.A. 84, 719-723).

PMID- 1975809
TI  - Analysis of the proliferating cell nuclear antigen promoter and its response to
      adenovirus early region 1.
AB  - The levels of the mRNA for the proliferating cell nuclear antigen (PCNA), a DNA
      replication factor, increase upon growth stimulation of quiescent cells. To study
      the transcriptional aspect of this response, we have cloned a PCNA gene fragment
      from size-fractionated human placental DNA. This fragment contains 1269
      nucleotides upstream from the PCNA transcriptional start site and includes an Alu
      sequence that is transcribed in vitro. The PCNA genomic DNA promotes
      transcription of a linked heterologous reporter gene in HeLa and 293 cells.
      Transient expression assays and in vitro transcription analyses showed that 249
      nucleotides of upstream sequence are sufficient for full promoter activity in
      HeLa cells, whereas only 172 nucleotides are needed in 293 cells. Co-transfection
      with a plasmid expressing the adenovirus E1 gene transactivates the PCNA promoter
      in HeLa cells. An E1-responsive element maps in the 85-nucleotide region
      immediately upstream of the site of transcription initiation.

PMID- 1975811
TI  - Differential regulation of beta 1- and beta 2-adrenergic receptor protein and
      mRNA levels by glucocorticoids during 3T3-F442A adipose differentiation.
AB  - The regulation by dexamethasone of beta 1- and beta 2-adrenergic receptor
      expression during the adipose differentiation of 3T3-F442A cells was investigated
      at the receptor protein and mRNA level. Preadipocytes were poorly responsive to
      beta-adrenergic receptor (beta-AR) agonists and expressed few beta-ARs
      (approximately 3,000 sites/cell) solely of beta 1 subtype. Differentiation
      increased adrenergic sensitivity and total beta-AR number (approximately 16,000
      sites/cell) with a beta 1/beta 2 ratio of approximately 90/10. Long term exposure
      of either differentiating cells or mature adipocytes to dexamethasone induced
      down-regulation of (-)-isoproterenol-sensitive adenylate cyclase activity which
      paralleled a 2- to 3.5-fold decrease in beta-ARs, while the beta 1/beta 2 ratio
      switched to approximately 20/80. The ratios of beta 1/beta 2 binding sites were
      always consistent with the rank order of potency of beta-adrenergic agonists in
      stimulating the adenylate cyclase system. The action of steroid agonists and
      antagonist suggested a glucocorticoid receptor-mediated mechanism. The beta 1-AR
      mRNA (3.2 kilobases) was stimulated 3-4.7 times in differentiated cells, as
      compared with preadipose cells; this beta 1-AR transcript was repressed in
      dexamethasone-treated cells. The beta 2-AR mRNA species (2.3 kilobases), absent
      in preadipocytes, was expressed at low levels in untreated adipocytes, but
      reached 11-fold this level in dexamethasone-exposed cells. The switch in receptor
      subtype protein and mRNA levels elicited by dexamethasone demonstrates the
      differential genetic control by glucocorticoids of beta-AR subtype expression in
      3T3-F442A cells. We suggest that this regulation of beta-AR gene expression
      requires interactions of glucocorticoid receptors with specific DNA targets and
      with one (or several) transcription factor(s) that are cell- and differentiation
      state-dependent.

PMID- 1975810
TI  - IL2-PE664Glu, a new chimeric protein cytotoxic to human-activated T lymphocytes.
AB  - To produce a molecule that will kill activated T cells as well as lymphomas and
      leukemias expressing interleukin 2 (IL2) receptors, we have created a recombinant
      chimeric protein in which IL2 is attached in peptide linkage to a truncated
      mutant form of Pseudomonas exotoxin (PE) (Lorberboum-Galski, H., FitzGerald,
      D.J.P., Chandhary, V.K., Adhya, S., and Pastan, I. (1988) Proc. Natl. Acad. Sci.
      U.S.A. 85, 1922-1926). Although this molecule was very active on rodent cells, it
      had lower activity on some human cell types. A new chimeric protein termed IL2
      PE664Glu has been constructed that is extremely toxic to both phytohemagglutinin
      blasts and mixed leukocyte reaction blasts prepared from monkey and human
      lymphocytes. The chimeric gene encoding this protein was constructed by fusing a
      cDNA clone for human interleukin 2 to the 5' end of a mutated cDNA encoding a
      full-length PE molecule. Four amino acids in domain I of PE were changed thus
      decreasing its nonspecific toxicity. IL2-PE664Glu is a much more active cytotoxic
      molecule for primate and human-activated T cells than IL2-PE40 which is a
      chimeric protein that was found to be an effective immunosuppressive agent in
      rodent models. Our results indicate that IL2-PE664Glu should be evaluated as an
      immunosuppressive agent for the treatment of human immune disorders in which
      activated T cells expressing the IL2 receptor are prominent.

PMID- 1975812
TI  - Two forms of DNA polymerase delta from mouse cells. Purification and properties.
AB  - A procedure is described for the purification from cultured mouse cells of two
      DNA polymerase "delta-like" enzymes, as defined by intrinsic 3'-exonuclease
      activity, inhibition by aphidicolin, and relative insensitivity to N2-(p-n
      butylphenyl)-dGTP. One of the two enzymes has been purified to near homogeneity
      and, similar to the DNA polymerase delta from calf thymus described by Lee et al.
      (Lee, M. Y. W. T., Tan, C. K., Downey, K. M., and So, A. G. (1984) Biochemistry
      23, 1906-1913), it has a total molecular mass of 178 kDa (from sedimentation
      velocity of 8.0 S and Stokes radius of 54 A) and is composed of one each of 125-
      and 50-kDa polypeptides. It also resembles the DNA polymerase delta of Lee et al.
      in being stimulated by proliferating cell nuclear antigen (PCNA). It is the first
      clear structural and functional counterpart of the calf thymus enzyme. The major
      difference between the mouse DNA polymerase delta and the calf thymus enzyme of
      Lee et al. is that, under specific conditions, the mouse enzyme is active with
      poly(dA).oligo(dT) in the absence of PCNA, whereas the activity of the calf
      thymus enzyme with this template is reported to be completely dependent on PCNA.
      The reason for this difference is not known at this time. The second mouse cell
      enzyme has a molecular mass of 112 kDa (from sedimentation velocity of 6.3 S and
      Stokes radius of 43.0 A) and consists of a single polypeptide of 123-125 kDa in
      denaturing gels (p125). On the basis of its apparent formation by dissociation of
      DNA polymerase delta, and multiple similarities with DNA polymerase delta in
      enzymatic properties, the p125 is provisionally identified as the 125-kDa
      polypeptide of DNA polymerase delta. The p125 does not respond to PCNA,
      suggesting that the 50-kDa polypeptide is required for the stimulation of DNA
      polymerase delta by PCNA. The presence of the p125 in cell extracts would explain
      reports that DNA polymerase delta consists of a single polypeptide of
      approximately 125 kDa and/or thast it has a smaller molecular mass than DNA
      polymerase delta of Lee et al. and is not affected by PCNA (this does not apply
      to PCNA-independent DNA polymerase delta-like enzymes with higher molecular mass
      than the polymerase delta of Lee et al., which have recently been named DNA
      polymerases epsilon).

PMID- 1975813
TI  - Competitive interaction of cyclosporins with the Vinca alkaloid-binding site of P
      glycoprotein in multidrug-resistant cells.
AB  - The mechanism of reversal of resistance to Vinca alkaloids by cyclosporins is
      unclear. We investigated the molecular mechanism of reversal of Vinca alkaloid
      resistance by cyclosporin A (CsA) and its nonimmunosuppressive analog O-acetyl
      C9(1) CsA (SDZ 33-243) in multidrug resistant DC-3F/VCRd-5L Chinese hamster
      cells. CsA at 3 microM increased vincristine (VCR) sensitivity and almost totally
      reversed VCR resistance. SDZ 33-243 at 1 microM reduced the IC50 for VCR in
      resistant cells from 62.0 to 0.00062 microM. CsA and SDZ 33-243 at 10 microM
      increased [3H]vinblastine (VBL) accumulation in DC-3F/VCRd-5L cells by 27- and 22
      fold, respectively. At 10 microM, these compounds also increased [3H]VCR
      accumulation by 3.5- and 4.0-fold, respectively. [3H]VCR uptake by membrane
      vesicles from DC-3F/VCRd-5L cells showed high and low affinity components with
      Michaelis-Menten kinetics, and apparent Km values were 0.140 +/- 0.0523 and 24.8
      +/- 6.67 microM, respectively. Kinetic analysis of [3H]VCR uptake in membrane
      vesicles in the presence of 0.2 microM CsA revealed that CsA competitively
      inhibited the high affinity [3H]VCR uptake with an apparent inhibition constant
      (Ki) of 0.126 +/- 0.0173 microM. In addition, CsA and SDZ 33-243 inhibited VBL
      photoaffinity labeling of P-glycoprotein in a dose-dependent manner, with half
      maximum inhibition at 0.5 and 0.4 microM, respectively, compared with that of VBL
      at 0.6 microM. These data confirm that cyclosporins modulate Vinca alkaloid
      resistance at least partially through interaction with P-glycoprotein.

PMID- 1975814
TI  - Clathrin-coated pits contain an integral membrane protein that binds the AP-2
      subunit with high affinity.
AB  - Coated pits will assemble onto purified plasma membranes that are attached to a
      poly-L-lysine coated substratum (Moore, M. S., Mahaffey, D. T., Brodsky, F. M.,
      and Anderson, R. G. W. (1987) Science 236, 558-563; Mahaffey, D. T., Moore, M.
      S., Brodsky, F. M., and Anderson, R. G. W. (1989) J. Cell Biol. 108, 1615-1624).
      To better understand the assembly reaction, we have purified both clathrin
      triskelion and AP-2 subunits from bovine brain and assayed for their ability to
      bind to the cytoplasmic surface of attached membranes. Two types of membranes
      were analyzed: those washed with a high pH buffer that selectively removes
      triskelions and those washed with a high salt buffer that removes both the AP-2
      and the triskelion subunits. We found that purified AP-2 subunits bind with high
      affinity (Kd approximately 3 x 10(-8) M) to salt stripped membranes. Binding is
      saturable and abolished by treating membranes with less than 20 micrograms/ml of
      elastase. When membranes were treated with elastase before the salt wash and then
      salt washed and assayed for AP-2 binding, normal binding was seen, which
      indicates that the presence of clathrin-coated pits protects the binding site
      from the protease. Membranes that had rebound AP-2 did not bind purified
      triskelions, even though high pH buffer-washed membranes that bear endogenous AP
      2 bound triskelions with high affinity (Kd approximately 3 x 10(-9) M) and
      supported lattice assembly. We conclude that coated pit assembly is initiated by
      the binding of AP-2 to an integral membrane protein but that the AP-2 complex
      must be activated by an unknown process before the coated pit lattice will
      assemble.

PMID- 1975816
TI  - Serum transglutaminase in inflammatory bowel diseases.
AB  - We evaluated the serum transglutaminase activity in patients with inflammatory
      bowel diseases (IBD) to correlate its level with clinical status. There were 49
      patients with Crohn's disease (CD), 50 with ulcerative colitis (UC), 35 with
      diseases other than IBD as control group and 42 healthy subjects matched for sex
      and age. Enzyme activity was significantly lower in both IBD groups than in
      controls and in normal subjects (p less than 0.001); we found a significant
      negative correlation between serum transglutaminase (TG) activity and clinical
      severity of the disease in both IBD patient groups (r = -0.54 in CD, and r = 
      0.69 in UC). Moreover, in UC and CD patients, a serum TG value lower than 0.80
      mU/ml retrospectively proved to predict the need for major surgery and/or total
      parenteral nutrition. These results suggest that serum TG may prove useful in the
      management of inflammatory intestinal diseases in predicting clinical outcome.

PMID- 1975815
TI  - ACTH-induced adrenal hemorrhage: a complication of therapy masquerading as an
      acute abdomen.
AB  - Four patients developed adrenal hemorrhage during treatment with intravenous
      adrenocorticotropic hormone (ACTH) for severe inflammatory bowel disease (IBD).
      This complication presented suddenly with upper abdominal and flank pain
      mimicking an acute surgical abdomen. In each patient the symptoms of the
      underlying bowel disease had subsided under the ACTH therapy. In our first
      patient the diagnosis was not made until laparotomy, but in the subsequent three
      patients the diagnosis was suspected by the strikingly similar clinical
      presentation. In each of these three latter patients the diagnosis was confirmed
      by sonography or computed tomography (CT) scan, and surgery was avoided. All four
      of our patients are doing well at 1-58 months of follow-up. Signs of adrenal
      insufficiency occurred only in the one of our four patients, and in those six of
      11 previously reported patients, who had bilateral adrenal hemorrhage. ACTH
      induced adrenal hemorrhage requires stopping ACTH and maintaining corticosteroid
      support. The diagnosis of adrenal hemorrhage should be considered in the patient
      treated with ACTH who develops unexplained acute abdominal or flank pain. Failure
      to recognize this complication of ACTH therapy can lead to unnecessary surgery or
      the dangerous continuation of the offending agent.

PMID- 1975817
TI  - Nodular regenerative hyperplasia of the liver: retrospective survey in autopsy
      series.
AB  - The frequency and pathogenesis of nodular regenerative hyperplasia of the liver
      (NRHL) were examined in general autopsy series. We found NRHL in 12 cases (2.1%)
      of 577 consecutive autopsy livers without hepatic necrosis, fibrosis, cirrhosis,
      or tumors. All of these cases were middle-aged to elderly adults, and there was a
      slight female predominance of 2:1. Symptoms related to the liver were absent in
      all but two cases. NRHL was an incidental finding in these 12 cases at autopsy.
      The main other diseases in these cases were classified into four groups: (a)
      organic cardiac diseases (four cases), (b) pulmonary diseases with right-sided
      cardiac hypertrophy (four cases), (c) small arterial diseases involving the liver
      (two cases), and (d) systemic amyloidosis involving intrahepatic small arterial
      branches (two cases). The frequency of NRHL in these four groups at autopsy was
      3.8, 7.1, 33.3, and 22.2%, respectively, suggesting that while NRHL is rare,
      clinicians should be aware of its association or development of NRHL in several
      conditions. Disturbances of outlet venous blood flow and inlet arterial blood
      flow may contribute to the development of NRHL in the former two and latter two
      groups, respectively.

PMID- 1975818
TI  - Ursodeoxycholic acid for primary sclerosing cholangitis.
AB  - The effects of ursodeoxycholic acid (UDCA, 750-1250 mg/day) were evaluated
      prospectively in 15 patients with primary sclerosing cholangitis (PSC). Five
      patients had associated inflammatory bowel disease. After 6 months of treatment,
      the proportion of patients suffering from fatigue or pruritus decreased from 60%
      to 20% and from 33% to 20%, respectively. No exacerbation of associated disorders
      was observed. Serum alkaline phosphatase levels (normal less than 100 IU/l)
      decreased from 401 +/- 53 to 222 +/- 42 (mean +/- S.E.; p less than 0.001), those
      of gamma-glutamyl transpeptidase, (normal less than 40 IU/l) from 520 +/- 89 to
      185 +/- 32 (p less than 0.001) and those of alanine aminotransferases, (normal
      less than 30 IU/l) from 79 +/- 12 to 42 +/- 6 (p less than 0.02). In three
      patients, the discontinuation of UDCA was associated with an aggravation of the
      liver test results. In conclusion, this study shows that 6 months of treatment
      with UDCA leads to clinical and biochemical improvements in patients with PSC.
      These results suggest that UDCA could be an effective treatment for PSC, and may
      justify a controlled therapeutic trial.

PMID- 1975819
TI  - Ursodeoxycholic acid for the treatment of primary biliary cirrhosis. Interim
      analysis of a double-blind multicentre randomized trial. The UDCA-PBC Study
      Group.
AB  - Based on uncontrolled observations, we have proposed ursodeoxycholic acid (UDCA)
      as a novel therapeutic approach in primary biliary cirrhosis (PBC). To confirm
      and extend our original findings, we have designed a double-blind multicentre
      randomized clinical trial. An interim analysis was planned at 6 months, involving
      all subjects included in the trial, with a final analysis at 2 years. The UDCA
      PBC trial began in June 1987 and will be completed in March 1990. Seventy
      patients were randomized to receive UDCA and 68 a placebo. The two groups were
      well matched with respect to age, sex, duration and prevalence of symptoms and
      histologic severity (50% of the UDCA group had stage III-IV disease vs. 37% of
      the placebo group). During the first 6 months of follow-up, six patients withdrew
      from the trial. At 6 months, the proportion of patients with jaundice was
      significantly lower (p less than 0.01) in UDCA recipients than in the placebo
      group. There was a similar decrease in the proportion of patients with pruritus
      and fatigue in both groups. The following laboratory test values were
      significantly lower in UDCA recipients than in the placebo group after 6 months
      of therapy: serum bilirubin, alkaline phosphatase, alanine aminotransferase
      (ALAT), aspartate aminotransferase (ASAT), gamma-glutamyltranspeptidase
      activities (p less than 0.001), cholesterol (p less than 0.003) and IgM levels (p
      less than 0.03). The results of this interim analysis confirm and extend the
      biochemical data provided by our previous pilot study. However the final analysis
      of the trial is necessary for a definitive assessment of the safety and efficacy
      of UDCA therapy in PBC.

PMID- 1975820
TI  - Regulatory function for murine intraepithelial lymphocytes. Two subsets of CD3+,
      T cell receptor-1+ intraepithelial lymphocyte T cells abrogate oral tolerance.
AB  - The murine intraepithelial lymphocyte (IEL) population is enriched in T cells
      that express the gamma delta-TCR, however, the biologic function served by these
      T cells remains obscure. IEL are considered to be major effector cells in mucosal
      immunity, and we have investigated whether IEL subsets could reverse orally
      induced systemic unresponsiveness (oral tolerance; OT) and support secondary type
      responses when adoptively transferred to mice orally tolerized with SRBC. When
      purified CD3+ IEL from mice orally primed with SRBC were transferred to adoptive
      hosts and challenged with SRBC, splenic IgM, IgG1, IgG2b, and IgA anti-SRBC
      plaque-forming cell responses were observed. However, CD3+ IEL from HRBC orally
      primed mice did not abrogate SRBC induced OT. Further, HRBC-primed CD3+, IEL
      converted HRBC-specific OT but not SRBC-specific OT. CD3+ IEL could be separated
      into four subsets based on expression of CD4 and CD8. CD3+, CD4-, 8+ T cells were
      the major subset (74.5%), with smaller numbers of CD4- and CD8- (double
      negatives, DN) (7.8%), CD4+, 8- (7.6%) and CD4+, CD8+ (double positives) (10.1%)
      T cells. Interestingly, both the CD3+, CD8+, and the CD3+, DN IEL subsets
      abrogated OT, resulting in significant IgM, IgG1, IgG2b, and IgA anti-SRBC plaque
      forming cell responses when adoptively transferred to mice with OT. However,
      neither CD3+, CD4+, CD8-, nor double positive T cells affected OT when studied in
      this system. The CD3+, CD8+ IEL subset could be further separated into Thy-1+
      (16.6%) and Thy-1- (83.4%) cells; adoptive transfer of Thy-1- cells abrogated
      oral tolerance whereas the Thy-1+ subset was without effect. When the expression
      of TCR on IEL with this biologic function was determined by use of monoclonal
      anti-alpha beta TCR (H57.597), TCR2-, CD3+ IEL possessed immunoregulatory
      function whereas the alpha beta-TCR+ (TCR2+) fraction did not abrogate OT.
      Immunoprecipitation of membrane fractions obtained from purified CD3+, CD4-,
      CD8+, Thy-1- IEL with polyclonal anti-delta peptide (Tyr-Ala-Asn-Ser-Phe-Asn-Asn
      Glu-Lys-Leu) antibody revealed bands of 45 and 35 kDa, corresponding to the delta
      and gamma-chains, respectively. These results suggest that gamma delta-TCR+ IEL
      possess a regulatory function, namely the restoration of immune responses in a
      state of oral tolerance. Further, both CD3+, CD4-, CD8+, Thy-1-, and CD3+, DN IEL
      T cells exhibit this effector contrasuppressor function.

PMID- 1975821
TI  - Suppressor cell clones specific for ultraviolet radiation-induced tumors.
      Function and surface proteins.
AB  - Lymphocytes were cloned from animals bearing UV-induced skin tumors. These cells
      were I-J+, CD4-, CD8-, and had become growth factor independent. Extracts, but
      not supernatants, of these clones suppressed primary immune reactions in vitro
      against UV-induced tumors, but not methylcholanthrene-induced tumors. The cells
      therefore had the functional characteristics of afferent suppressor T cells
      directed against a common Ag on UV-induced tumors. Surface iodination of the
      clones revealed an extremely low level expression of molecules that might be TCR
      or related molecules.

PMID- 1975822
TI  - Failure of infiltrating precursor cytotoxic T cells to acquire direct cytotoxic
      function in immunologically privileged sites.
AB  - Minor H incompatible P815 tumor cells inoculated into the anterior chamber (AC)
      of the eyes of BALB/c mice grow progressively, revealing this to be an
      immunologically privileged site. By contrast, a similar inoculation of tumor
      cells is rapidly rejected from nonprivileged ocular sites (subconjunctiva). Mice
      with progressively growing AC-tumors and those that reject their ocular
      subconjunctiva tumors both have expanded clones of tumor-specific cytotoxic
      precursor cells (pTc) in their spleens and cervical lymph nodes. In an effort to
      determine why the expanded pool of primed pTc is unable to effect rejection of AC
      intraocular tumors, we have examined the susceptibility of the tumor cells
      growing within the immunologically privileged AC to lysis by cytotoxic T cells
      and the cytotoxic function of tumor-infiltrating lymphocytes. P815 tumor cells
      extracted from intraocular tumors and P815 cells maintained in routine tissue
      culture are equally susceptible to lysis when exposed in vitro to fully
      differentiated, DBA/2-specific cytotoxic T cells. Thus, progressively growing
      tumor cells within the AC are not insensitive to immune-mediated lysis by
      cytotoxic T cells. We have been able to harvest significant numbers of DBA/2
      specific pTc from these same intraocular tumors. When the tumor-infiltrating
      lymphocytes are driven in vitro with exogenous IL-2, they acquire the capacity to
      lyse specifically P815 tumor cells. However, no evidence of fully cytotoxic,
      tumor-specific T cells was found among lymphocytes harvested from intraocular
      tumors, i.e., when the harvested cells were tested immediately for cytolytic
      activity. Inasmuch as we have reported that directly cytotoxic T cells are
      present during tumor rejection at nonimmunologically privileged ocular sites,
      such as the subconjunctival space, we conclude that progressive growth of P815
      tumor cells within the anterior chamber is due in part to a failure of
      infiltrating pTc to differentiate in situ into fully functional cytotoxic
      effector cells.

PMID- 1975823
TI  - sgp-60, a signal-transducing glycoprotein concerned with T cell activation
      through the T cell receptor/CD3 complex.
AB  - T cell activation depends not only on the expression of a TCR, but also on that
      of accessory molecules that function in cell-cell adhesion and/or signal
      transduction. The subject of this report is the biochemical and functional
      characterization of what appears to be a novel murine lymphocyte cell surface
      antigen, provisionally termed sgp-60. Extensive, higher-order cross-linking of
      this glycoprotein with an anti-sgp-60 mAb and a second-step antibody reagent
      results in the activation of resting CD4+ T cells in the presence of a second
      signal. Monovalent or bivalent engagement of sgp-60 by the anti-sgp-60 antibody
      results in profound and direct inhibition of anti-CD3- or Con A-driven T cell
      activation, whereas alternative T cell activation via the phosphatidylinositol
      linked proteins Thy-1 and TAP/Ly-6A is not affected. These findings raise the
      possibility that the sgp-60 molecule may be specifically involved in signal
      transduction through the TCR/CD3 complex and thus point to an important
      physiologic role for this protein in CD4+ T cells.

PMID- 1975824
TI  - Low dose ultraviolet B-irradiated Langerhans cells preferentially activate CD4+
      cells of the T helper 2 subset.
AB  - UVB radiation distorts the Ag-presenting function of epidermal Langerhans cells
      (LC); this has been shown for the presentation of soluble Ag to primed T cells in
      vitro and for the initiation of delayed-type hypersensitivity in vivo, such as
      contact hypersensitivity (CH). Previous work has also demonstrated UVB-induced
      suppression of CH to be mediated ultimately by T cells. Two subsets of CD4+ Th
      cells, Th1 and Th2, have been identified, based on their cytokine production and
      functional activities. In particular, Th1 mediate delayed-type hypersensitivity,
      whereas Th2 do not. To investigate whether the perturbation of LC function
      induced by UVB radiation leads to a differential activation of these subsets of
      CD4+ cells, we examined the capacity of unirradiated and irradiated (200 J/m2)
      APC from adult BALB/c mice to present keyhole limpet hemocyanin to Ag-specific,
      H2d-restricted Th1 and Th2 cell lines. Four sources of APC were utilized:
      epidermal cells (EC), flow microfluorometry-purified Ia+ EC (LC), flow
      microfluorometry-purified Ia- EC, and splenic adherent cells (SAC). Unirradiated
      EC, LC, and SAC, but not Ia-EC, presented keyhole limpet hemocyanin to both Th1
      and Th2. Irradiated EC and LC lost their ability to stimulate Th1, but retained
      fully their capacity to stimulate Th2. On the other hand, irradiated SAC were
      unable to induce proliferation of either Th1 or Th2. These findings indicate that
      suppression of CH mediated by UVB-irradiated LC may result from an alteration of
      the ratio and/or activity of Th1 and Th2 cells normally generated during the
      induction of such responses.

PMID- 1975825
TI  - Induction of graft versus host-associated immunodeficiency by CD4+ T cell clones.
AB  - Previous studies have shown that the injection of parental T cells into MHC class
      II mismatched F1 recipient mice can lead to graft-vs-host (GvH) reaction that
      manifests itself by multiple symptoms. The objective of our study was to analyze
      GvH reactivity induced by a single T cell clone specific for host I-A or I-E
      alloantigen. The T cell clones tested for GvH potential were CD4+, with or
      without cytolytic activity in vitro and with a lymphokine pattern that classifies
      them as Th1 cells. The inoculation of a single T cell clone induced a severe, but
      transient immunodeficiency in the host that was independent of its cytolytic
      activity, as demonstrated by the failure to generate a CTL response to third
      party allogeneic cells in vitro. Induction of immunodeficiency in the recipients
      required preactivation of the clones in vitro by rIl-2 and the presence of the
      stimulator class II alloantigen in the host. Spleen cells from these mice lacked
      suppressor cells, they were deficient in Il-2 secretion and exhibited a decrease
      in the number of CD4+ T cells. In addition, I-E expression was reduced, however,
      without any changes in the macrophage population and an increase in surface Ig
      and the B cell marker B220. Simultaneous to the immunodeficiency, the clone
      injected mice produced elevated antibody titers to ssDNA.

PMID- 1975826
TI  - CD4-CD8- T cells from mice with collagen arthritis display aberrant expression of
      type l K+ channels.
AB  - Expression of voltage-gated K+ channels in mAb-defined T cell subsets from normal
      mice and mice with experimental autoimmune arthritis was studied with the patch
      clamp whole-cell recording technique in combination with fluorescence microscopy.
      CD4+CD8- Th cells from DBA/1 LacJ mice with type II collagen arthritis expressed
      low levels of type n K+ channels, and CD4-CD8+ T cells (cytotoxic) showed small
      numbers of type l or n' K+ channels, like their phenotypic counterparts in normal
      mice. CD4-CD8-Thy-1.2+ (double negative or DN) T cells from the diseased mice,
      however, displayed an abundance of type l K+ channels compared to DN T cells in
      normal mice, or mice immunized with CFA. Furthermore, the aberrant expression of
      type l K+ channels correlated with the presence of active disease. DN T cells
      from mice with SLE, type-1 diabetes mellitus, and experimental allergic
      encephalomyelitis, also exhibited a high number of type l K+ channels. These
      results suggest that expression of numerous type l K+ channels may be a useful
      marker for DN T cells associated with these autoimmune disorders.

PMID- 1975827
TI  - Frequency analysis of lymphokine-secreting CD4+ and CD8+ T cells activated in a
      graft-versus-host reaction.
AB  - Lymphokine secretion by in vivo-activated T cells was analyzed at the population
      and single-cell levels in lymphocytes from mice undergoing an acute allogeneic
      graft-vs-host reaction (GVHR). Three observations were made. First, constitutive
      lymphokine production by these cells was very low but could be dramatically up
      regulated by TCR ligation. Thus, even when harvested at the peak of the GVHR,
      fewer than 0.1% of lymphocytes secreted detectable granulocyte-macrophage (GM)
      CSF, IFN-gamma, or IL-3 in the first 24 h in vitro, and average production of
      these lymphokines in bulk cultures was less than 10(-5) U/cell. However, when
      cultured for 24 h with anti-CD3 antibody under conditions which activated less
      than 0.1% of normal cells, about 30% of GVHR T cells secreted GM-CSF, IFN-gamma,
      and/or IL-3, and average production levels were increased by 10(3)- to 10(4)
      fold. Together with evidence that host alloantigen-induced lymphokine secretion
      was 10 to 100 times lower than the anti-CD3 response, these data suggest that
      physiologic lymphokine synthesis by most T cells is low (less than 10(-18) mol of
      IL-3 per cell) but can be raised above the threshold of detection by TCR cross
      linking. Second, individual GVHR lymphocytes varied markedly in their total and
      relative production of different lymphokines in response to anti-CD3 stimulation,
      with some cells secreting IL-3 alone, some secreting IL-3 accompanied by other
      lymphokines (GM-CSF and/or IFN-gamma), and some secreting other lymphokines
      without detectable IL-3. Finally, both CD4+ and CD8+ T cells from GVHR mice
      responded to anti-CD3 antibody by secreting IL-3 and other lymphokines: purified
      CD4+ cells contained an average of 16% and CD8+ cells an average of 10% anti-CD3
      inducible lymphokine-secreting cells. By contrast, only 2 to 3% of cells of
      either subset formed clones in cultures with host allogeneic cells and IL-2,
      suggesting that clonogenic alloreactive cells were a minority of the T cells
      activated in the GVHR.

PMID- 1975828
TI  - Chromosomal location of the Ly-49 (A1, YE1/48) multigene family. Genetic
      association with the NK 1.1 antigen.
AB  - The Ly-49 (A1, YE1/48) Ag is a disulfide-linked dimer with 44-kDa subunits, and
      is expressed on the cell surface of rare T cell tumors of C57BL/6 origin.
      Although this Ag is undetectable by flow microfluorimetry analysis, normal cells
      have been shown to express the A1 Ag by immunoprecipitation experiments performed
      on surface radioiodinated spleen and thymus cells. We (J. Immunol. 143:1379,
      1989) and others (J. Immunol. 142:1727, 1989) have recently isolated cDNA
      encoding the Ly-49 Ag. Southern blots with an Ly-49 cDNA probe revealed multiple
      bands, consistent with cross-hybridization to other members of a multigene
      family, and significant RFLP between the C57BL/6 and BALB/c strains. When the
      RFLP patterns displayed by other common laboratory strains as well as informative
      recombinant inbred strains were examined, the Ly-49 gene family displayed five
      RFLP patterns and the entire family was found to reside on a contiguous stretch
      of the distal portion of mouse chromosome 6, the same region to which the NK1.1
      Ag has been mapped. Although tissue distribution studies and transfection
      analysis ruled out the possibility that Ly-49 was identical to NK1.1 Ag,
      approximately 20% of NK1.1 cells isolated from normal spleen coexpressed Ly-49
      and all Ly-49+ cells were CD3-. Although spleen cells cultured in high doses of
      rIL-2 demonstrated similar coexpression of NK1.1 and Ly-49, approximately 10% of
      CD3+ cells coexpressed Ly-49. The chromosomal mapping data and the expression of
      the Ly-49 and NK1.1 Ag suggest that the NK1.1 Ag may be a member of the Ly-49
      multigene family.

PMID- 1975829
TI  - Autologous melanoma-induced activation of regulatory T cells that suppress
      cytotoxic response.
AB  - The host immune response toward autologous human cancer is subject to regulation
      by the immunoregulatory network. We show that certain CD4+ T cell clones, derived
      from melanoma involved lymph node lymphocytes and from PBL stimulated by
      autologous melanoma cells, selectively down-regulated the induction of cytotoxic
      immune response of PBL against the respective autologous melanoma cells in two
      autologous systems. In both systems, only the generation of cytotoxic response
      against the autologous melanoma cells were suppressed. Cytotoxic response against
      EBV-infected autologous lymphoblastoid cell line in one case and cytotoxic
      responses against allogeneic targets in the other were not affected. In addition
      to suppressor activity selectively expressed against the autologous melanoma
      cells, the T cell clones up-regulated their Tac receptors when cocultured with
      the autologous melanoma cells and APC. These results support the existence of a
      putative tumor Ag-driven activation of regulatory T cells that affect cytotoxic
      immune response, in vitro, against autologous human melanoma.

PMID- 1975830
TI  - Granulated metrial gland cells of pregnant mouse uterus are natural killer-like
      cells that contain perforin and serine esterases.
AB  - The mouse uterus during pregnancy contains a large population of lymphoid cells
      termed granulated metrial gland (GMG) cells. Our observations suggest that these
      cells are highly activated cytolytic lymphocytes related to NK or lymphokine
      activated killer cells. Immunostaining demonstrated asialo GM1 and Thy-1 on GMG
      cells, both of which are expressed by NK cells. Decidua basalis tissue and
      isolated GMG cells contained three proteins that are characteristic of activated
      cytolytic lymphocyte granules: perforin, serine esterase 1, and serine esterase
      2. These mediators were demonstrated in GMG cells by Western blot analysis using
      polyclonal antisera and by Northern blot analysis using specific cDNA probes for
      their mRNA. The proteins were not detected in normal spleen or liver or in asialo
      GM1+ cells isolated from those organs, consistent with the absence of these
      mediators from resting cytolytic cells. The amount of perforin in GMG cells was
      similar to that present in cloned, IL-2-stimulated, CTL shown previously to
      contain a large amount of this protein. A large population of NK cells bearing
      the surface marker LGL-1 was demonstrated at the implantation site by labeling
      with monoclonal antibody 4D11, but T cells were not detected. Many LGL-1+ cells
      at the implantation site expressed the GMG cell markers asialo GM1, Thy-1, and
      perforin. Staining intensities were inversely correlated, with LGL-1-bright cells
      showing little or no staining of GMG cell markers and LGL-1-faint cells showing
      more obvious staining of GMG cell markers. This suggests that LGL-1+ NK cells may
      differentiate in situ to GMG cells, losing LGL-1 and gaining a high concentration
      of GMG cell markers in the process. Activated cytolytic cells related to NK or
      lymphokine-activated killer cells may function in the pregnant rodent uterus to
      intercept and kill aberrant placental or embryonic cells that might otherwise
      enter the female and proliferate.

PMID- 1975831
TI  - [The clinical significance of serum sialyl SSEA-1 antigen in obstetrical and
      gynecological patients].
AB  - To evaluate the clinical significance of serum SSEA-1 level, the antigen level
      was measured in sera of obstetric and gynecologic patients. A positive rate was
      low in patients with endometriosis (9.1%), myoma uteri (0%), benign ovarian tumor
      (15%), cervical squamous cell carcinoma (14%) and endometrial carcinoma (18%). In
      this series of study, interest was that positive cases in benign ovarian tumor
      group were all patients with dermoid cyst. On the other hand, a high positive
      rate was observed among the patients with cervical adenocarcinoma (50%), primary
      ovarian malignancies (55%) and secondary ovarian malignancies (50%). Among the
      patients with ovarian malignancies, serum sialyl SSEA-1 level significantly
      increased according to clinical stage. In patients with positive serum sialyl
      SSEA-1, rising or falling of the serum level of this antigen correlated well with
      progression or regression of the disease. Measurement of serum CA125 was also
      performed in patients with ovarian malignancies, which showed a significantly
      higher positive rate (96%) and revealed that this antigen has no correlation with
      sialyl SSEA-1. A low positive rate of serum sialyl SSEA-1 level (9.1%) was
      observed in gravidas, while a higher positive rate (43%) in puerperas, especially
      within three days after parturition. This evidence should be considered when
      serum sialyl SSEA-1 antigen is measured as tumor marker. All these observations
      suggest that the measurement of serum sialyl SSEA-1 level is useful not only in
      the diagnosis of ovarian malignancies but for the judgment of the effect of
      treatment and the search for their recurrences.

PMID- 1975832
TI  - [A long survived case of malignant pheochromocytoma treated with alpha-methyl-p
      tyrosine and midaglizol (DG-5128)].
AB  - Survival period of malignant pheochromocytoma treated only conservatively is
      reported to be less than one year by T. Sato. A patient of malignant
      pheochromocytoma with liver metastasis has been treated with alpha-methyl-p
      tyrosine (alpha MPT), tyrosine hydroxylase inhibitor, in the last 5 years.
      Catecholamine levels markedly decreased and he has a long survival time. He lives
      over 17 years from the detection of malignant pheochromocytoma. alpha MPT was
      considered to have a role to protect a patient from cardiomyopathy induced by
      hyper-catecholaminemia and to have the action of inhibiting the growth of this
      tumor. The growth of this tumor was very slow. Since this case had insulin
      independent diabetes mellitus, insulin therapy was applied, however, blood
      glucose level was not controlled well. Then we tried midaglizol (DG-5128), alpha
      2-adrenoceptor antagonist, to control diabetes mellitus and a sufficient control
      was obtained. C-peptide level in urine was increased concomitant with decrease of
      blood glucose. This fact suggested that insulin secretion was improved. It is
      well known that catecholamine, especially noradrenaline has an inhibiting action
      on insulin secretion from beta cell. This action was appeared through alpha 2
      adrenergic receptor. DG-5128 has an action as alpha 2-adrenoceptor antagonist. We
      think an inhibiting action on insulin secretion of catecholamine was diminished
      through its action as adrenoceptor antagonist. Kawazu et al. reported that
      catecholamine levels, heart rate and blood pressure did not change by DG-5128
      administration in healthy subjects. In this patient, no change was appeared
      either. No major complication was observed during this treatment.

PMID- 1975833
TI  - Transposon-induced non-motile mutants of Vibrio cholerae.
AB  - Non-motile mutants of Vibrio cholerae were isolated after transposon insertion
      mutagenesis with either Tn5 on a plasmid or Tn10ptac mini-kan in bacteriophage
      lambda. The physical location and number of transposon insertions was determined.
      Eighteen Tn5 insertion mutants and 11 Tn10ptac mini-kan insertion mutants had
      single unique insertion sites. The 18 Tn5 insertions were contained within six
      different EcoRI fragments and the 11 Tn10ptac mini-kan insertions were contained
      within eight different fragments of V. cholerae chromosomal DNA. These data
      suggest that multiple genes are involved in motility. Immunoblot analysis of non
      motile mutants with antibody to wild-type flagellar core protein indicated that
      two of the non-motile mutants made flagellar core protein. Three additional
      mutants reacted weakly with the antibodies. However, these mutants with
      immunopositive reactions did not produce any structures which resembled flagella
      by transmission electron microscopy. In addition, none of the other non-motile
      mutants produced wild-type flagella. However, five mutants which did not react in
      the immunoblot produced a structure which resembled a flagellar sheath without
      the internal flagellar core. In addition to having no filamentous core, the
      sheaths often extended from the sides of the bacteria, rather than from the poles
      where the flagellum is normally located. The data suggest that sheath formation
      is independent of flagellar filament formation, but that proper positioning of
      the sheath may require the flagellar filament.

PMID- 1975834
TI  - Attaching and effacing lesions in vivo and adhesion to tissue culture cells of
      Vero-cytotoxin-producing Escherichia coli belonging to serogroups O5 and O103.
AB  - Certain isolates of Escherichia coli from humans and animals with enteric disease
      attach to enterocytes and cause 'attaching and effacing' (AE) lesions. E. coli
      strain S22-1, serotype O103:H2, isolated from a child with diarrhoea, contained
      two plasmids; one of these (pDEP12) hybridized with the CVD419 DNA probe derived
      from a plasmid found in E. coli O157:H7 and associated with expression of
      fimbriae and ability to adhere to Intestine 407 cells. Strain S102-9, serotype
      O5:H-, isolated from a calf with dysentery, contained six plasmids, one of which
      also hybridized with the CVD419 probe. Loss of pDEP12 coincided with reduced
      adhesion to HEp-2 or Intestine 407 cells cultured in vitro; reintroduction of
      this plasmid restored adhesiveness. Loss of the plasmid in strain S102-9 that
      hybridized with the CVD419 probe did not cause a decrease in adhesion.
      Accumulations of actin were seen in vitro in the fluorescence actin staining
      (FAS) test of strains S22-1, S102-9 and their derivatives, irrespective of the
      plasmid content of these strains or the prevalence of attached bacteria. Strain
      S22-1 and its plasmidless derivative caused AE lesions of equal severity in
      experimentally infected gnotobiotic piglets; piglets inoculated with an isolate
      from a healthy human or pig did not develop these lesions.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1975835
TI  - Stereoselectivity for the (R)-enantiomer of HA-966 (1-hydroxy-3-aminopyrrolidone
      2) at the glycine site of the N-methyl-D-aspartate receptor complex.
AB  - HA-966 (1-hydroxy-3-aminopyrrolidone-2) is an antagonist at the glycine
      allosteric site of the N-methyl-D-aspartate receptor ionophore complex. Unlike
      presently known glycine antagonists, HA-966 is chiral. We report
      stereoselectivity for the (R)-enantiomer at the glycine antagonist site. In
      [3H]glycine binding, the (R)-enantiomer has an IC50 of 4.1 +/- 0.6 microM. The
      racemic mixture has an IC50 of 11.2 +/- 0.5 microM, whereas (S)-HA-966 has an
      IC50 greater than 900 microM. In glycine-stimulated [3H]1-[1-(2-
      thienyl)cyclohexyl]piperidine binding, the (R)-enantiomer inhibits with an IC50
      of 121 +/- 61 microM, whereas the racemic mixture has an IC50 of 216 +/- 113
      microM and (S)-HA-966 is inactive. The inhibition by (R)-HA-966 can be prevented
      by the addition of glycine. (R)-HA-966 and racemic HA-966, but not (S)-HA-966,
      also prevent N-methyl-D-aspartate cytotoxicity in cortical cultures. The (R)
      enantiomer and, less potently, the (S)-enantiomer inhibit N-methyl-D-aspartate
      evoked [3H]norepinephrine release from rat hippocampal slices (IC50 values of
      about 0.3 mM and 1.6 mM, respectively), but only the inhibition by (R)-HA-966 is
      reversed by added glycine. In glutamate-evoked contractions of the guinea pig
      ileum, (R)-HA-966 causes a glycine-reversible inhibition (IC50 of about 150
      microM), whereas (S)-HA-966 is much less potent (IC50 of greater than 1 mM).
      These results demonstrate stereoselectivity of the glycine antagonist site of the
      N-methyl-D-aspartate receptor complex in a variety of tissues and assays. The
      stereoselectivity also confirms the specificity of N-methyl-D-aspartate receptors
      in glutamate-evoked contractions of the guinea pig ileum, and supports their
      similarity to central N-methyl-D-aspartate receptors.

PMID- 1975836
TI  - Gene expression of tyrosine hydroxylase in the developing fetal brain.
AB  - Tyrosine hydroxylase, aromatic L-amino-acid decarboxylase, and dopamine beta
      hydroxylase activities were studied in the developing fetal rat brain. A delay of
      2-3 days between the detection of the tyrosine hydroxylase and the aromatic L
      amino-acid decarboxylase and dopamine beta-hydroxylase activities was observed.
      For this reason, the expression of tyrosine hydroxylase mRNA was studied.
      Tyrosine hydroxylase mRNA was visualized in the whole brain from 13 days of
      gestation, but the largest increase of the expression was observed in the
      hypothalamus. These results are discussed in terms of the relative gene
      expressions of the three enzymes involved in the biosynthesis of catecholamines
      and phenolamines in nervous tissues.

PMID- 1975837
TI  - Excitatory amino acid-induced formation of inositol phosphates in guinea-pig
      cerebral cortical slices: involvement of ionotropic or metabotropic receptors?
AB  - In cerebral cortical slices from the guinea-pig, quinoxalinedione derivatives
      antagonised the generation of 3H-inositol phosphates evoked by the excitatory
      amino acids quisqualate and DL-alpha-amino-3-hydroxy-5-methyl-4-isoxalone
      propionic acid but were without effect on the trans-DL-1-amino-1,3
      cyclopentanedicarboxylic acid and L-glutamate responses. Omission of calcium from
      the medium reduced the accumulation of 3H-inositol phosphates induced by
      incubation with trans-DL-1-amino-1,3-cyclopentanedicarboxylic acid (incubation
      for 45 min) by greater than 50%, whereas the responses to L-glutamate and the two
      other amino acid analogues were reduced by approximately 20%. Generation of
      inositol 1,4,5-trisphosphate over a 30-s period by treatment with quisqualate,
      trans-DL-1-amino-1,3-cyclopentane-dicarboxylic acid, KCl, and carbachol was
      abolished in the presence of nominally calcium-free medium. L-Glutamate induced a
      large, rapid increase in inositol 1,4,5-trisphosphate mass (more than three
      fold), which was, however, unaffected by omission of calcium from the medium.
      These results indicate that of the excitatory amino acids tested, only L
      glutamate may be classed as a metabotropic receptor agonist in guinea-pig
      cerebral cortical slices with respect to generation of inositol phosphates. The
      other agents appear to stimulate accumulation of inositol phosphates, at least in
      part through some mechanism requiring the presence of extracellular Ca2+,
      presumably Ca2+ entry.

PMID- 1975838
TI  - Asynchronous appearance and topographic segregation of neuropeptide-containing
      cells in the developing rat adrenal medulla.
AB  - The developmental expression of neuropeptide Y (NPY) and leucine-enkephalin (L
      Enk) was examined in embryonic, early postnatal, and adult chromaffin cells with
      double- and triple-label immunocytochemical techniques and compared to the
      expression of immunoreactivity for tyrosine hydroxylase (TH) and
      phenylethanolamine N-methyltransferase (PNMT). In addition, the establishment of
      preganglionic innervation was assessed by labeling for choline acetyltransferase
      (ChAT) and L-Enk. NPY-IR was detectable on embryonic (E) day 15 in a clustered
      subpopulation of TH-IR cells. L-Enk and PNMT-IR cells were initially present on
      E16 in a separate nonclustered population of TH-IR cells. By late embryonic
      development, twice as many TH-IR cells expressed NPY and 4 times as many
      expressed L-Enk as in the adult. In contrast to early embryonic development, NPY
      IR was evident in both the clustered and nonclustered subpopulation of TH-IR
      cells at this time. The proportion of NPY-IR chromaffin cells decreased to adult
      values during the first postnatal week at the time when obviously clustered TH-IR
      cells were no longer observed. The embryonic rise in the proportion of L-Enk-IR
      cells correlates with the developmental increase in glucocorticoid production,
      while the postnatal decrease corresponds to the appearance of ChAT-IR in the
      preganglionic innervation of the adrenal medulla. These results indicate that NPY
      and L-Enk are expressed at different times and in different subpopulations of
      cells in the embryonic adrenal. Further, the observation that peptide expression
      by chromaffin cells undergoes marked changes during development raises the
      possibility that a number of factors including developmental history,
      environmental signals and impulse activity play a role in the regulation of
      neuropeptide expression in sympathoadrenal derivatives of the neural crest.

PMID- 1975839
TI  - Ultrastructural localization of tyrosine hydroxylase in the rat ventral tegmental
      area: relationship between immunolabeling density and neuronal associations.
AB  - Dopaminergic neurons of the A 10 cell group in the rat ventral tegmental area
      (VTA) exhibit electrical and dye coupling. Also, the activity of these neurons at
      least partially reflects their content of tyrosine hydroxylase (TH), the rate
      limiting enzyme in catecholamine biosynthesis. We examined the ultrastructural
      localization of TH to determine the morphological features of dopaminergic
      neurons in the VTA and the relationships between their TH immunoreactivity
      content and afferent input. Antiserum against the trypsin-treated form of TH was
      localized using peroxidase-antiperoxidase (PAP) and immunoautoradiographic
      methods. Immunoreactivity was detected in perikarya, dendrites, and terminals.
      The perikarya contained the usual organelles, as well as cilia, lamellar bodies,
      and subsurface cisterns. Qualitative evaluation of peroxidase reaction product
      and quantitative analysis of the number of silver grains/unit area revealed
      varying amounts of TH immunoreactivity in nuclei and cytoplasm. Lightly or
      intensely labeled nuclei were not necessarily associated with corresponding
      cytoplasmic labeling density. However, cytoplasmic labeling directly corresponded
      to the relative frequencies of neuronal appositions and synaptic input. Those
      neurons with less dense cytoplasmic PAP product received fewer synaptic contacts
      and were less frequently in apposition to other TH-labeled soma and dendrites
      than neurons displaying relatively more dense cytoplasmic PAP product. Analysis
      of single sections revealed that 67% (n = 71) of all TH-labeled somata and 15% (n
      = 2431) of all TH-labeled dendrites were in apposition to other TH-labeled soma
      or dendrites. TH-labeled terminals were rarely detected and contained relatively
      low levels of immunoreactivity. The majority of labeled terminals (n = 29/46)
      formed synapses with labeled soma and dendrites. Unlabeled terminals (n = 2424)
      in contact with TH-labeled dendrites appeared to form predominantly symmetric
      synapses. Ten percent (n = 248) of the unlabeled terminals dually synapsed onto
      adjacent immunoreactive dendrites, perikarya, or dendrite and perikaryon. We
      conclude that in the rat VTA, (1) detected TH immunoreactivity in cytoplasm, but
      not nucleus, corresponds to the level of feedback principally from
      nondopaminergic afferents; (2) dendrodendritic as well as axodendritic synapses
      between TH-immunoreactive neurons may mediate dopaminergic autoinhibition; and
      (3) gap junction-like appositions between neurons and convergent inputs from
      unlabeled terminals onto TH-immunoreactive profiles provide an anatomical
      substrate whereby cellular activities might be coordinated under certain
      conditions.

PMID- 1975841
TI  - Establishment of permanent astroglial cell lines, able to differentiate in vitro,
      from transgenic mice carrying the polyoma virus large T gene: an alternative
      approach to brain cell immortalization.
AB  - Permanent untransformed cell lines have been established from the cerebral cortex
      of transgenic mice that carry the polyoma virus large T gene. The immortalized
      cells described here synthesize laminin and neural cell adhesion molecules and
      induce primary neurons to develop neuritic processes. As shown by
      immunofluorescence and immunoblotting assays, they begin to synthesize the glial
      fibrillary acidic protein (GFAP) after confluence. Double labelling experiments
      indicated that GFAP expression is reversibly correlated with the arrest of cell
      division. The present cells also display adrenergic, serotoninergic, and high
      levels of muscarinic receptors coupled to the phosphatidylinositol signalling
      pathway. Taken together, our data show that these cell lines constitute
      homogeneous cell material that has retained the main differentiative, functional,
      and growth properties of normal astrocytes. Therefore, such clonal untransformed
      cell lines should be useful for further molecular studies, addressing terminal
      differentiation of glial cells, glioneuronal interactions, and astroglial
      expression of receptors for neurotransmitters. Furthermore, we suggest that this
      approach of cell immortalization by the use of transgenic mice carrying a non
      transforming oncogene might be extended to a variety of cell types.

PMID- 1975840
TI  - Assay and disposition of carvedilol enantiomers in humans and monkeys: evidence
      of stereoselective presystemic metabolism.
AB  - Carvedilol is a new beta-blocking agent with vasodilating activities, which is a
      racemic mixture of R(+)- and S(-)-enantiomers. Since the two enantiomers differ
      in pharmacological properties, it is necessary to individually measure their
      plasma concentrations in order to evaluate the pharmacological effects of racemic
      carvedilol after oral administration. In this study, a sensitive, stereospecific
      high-performance liquid chromatographic assay was used to determine the plasma
      concentration of each enantiomer. The assay involves the diastereomeric
      derivatization of racemic carvedilol with 2,3,4,6-tetra-O-acetyl-beta-D
      glucopyranosyl isothiocyanate as a chiral reagent. After oral administration of
      racemic carvedilol to humans, the mean Cmax and AUC infinity values for R(+)
      enantiomer were 2.6 and 2.8 times greater, respectively, than those for the more
      active S(-)-enantiomer. Similarly, in monkeys, the respective R:S enantiomer
      ratios for Cmax and AUC infinity were 1.5 and 1.2. The difference in AUCoral
      between these enantiomers is ascribed to the greater intrinsic clearance of S(-)
      enantiomer than that of the R(+)-enantiomer in the liver, and to a lower plasma
      protein binding of the S(-)-enantiomer.

PMID- 1975842
TI  - Opioids influence neurotransmitter phenotypic expression in chick embryonic
      neuronal cultures.
AB  - There is considerable interest in the role of endogenous opioid peptides in
      neural growth and differentiation. In this study we used neuron-enriched cultures
      derived from 3-day-old chick embryos to test the effects of endogenous
      enkephalins on neurotransmitter phenotypic expression. Cultures were grown in
      serum-free chemically defined medium and were treated with either Met-enkephalin
      antiserum (anti-Met) to immunoneutralize enkephalins, or with naloxone, a
      universal opioid receptor antagonist, to block receptor-mediated actions of
      released endogenous opioids. The enzyme activities of choline acetyltransferase
      (ChAT) and tyrosine hydroxylase (TH) were used as markers for cholinergic and
      catecholaminergic phenotypic expression, respectively. We found that cultures
      treated with anti-Met or naloxone exhibited strikingly different neuronal growth
      patterns as compared to controls. In addition, ChAT activity was enhanced by anti
      Met, and TH activity by both anti-Met and naloxone. These findings lend support
      to the possibility that neuropeptides may be co-localized with neurotransmitters
      and that peptides released into the microenvironment affect neuronal phenotypic
      expression by differential receptor subtypes.

PMID- 1975843
TI  - Cooperation of v-jun and v-erbB oncogenes in embryo fibroblast transformation in
      vitro and in vivo.
AB  - Retroviral vectors carrying either the v-jun and v-erbB sequences or the v-jun
      gene linked to the neomycin resistance gene were constructed on the basis of the
      structural genome organization of avian erythroblastosis virus (AEV). These
      viruses, called JB and JN, respectively, were rescued as Rous-associated virus-1
      pseudotypes, and they were shown to successfully transform chicken embryo
      fibroblasts in vitro. However, in agar, colonies developed from JB-infected
      fibroblasts were three to five times larger than those obtained after infection
      with JN or with AEV Pst124 carrying only a functional v-erbB gene. In vivo, on
      chorioallantoic membrane (CAM) assays, JB produced fibrosarcomas that were more
      rapidly growing and much larger than those induced by JN or AEV Pst124. Moreover,
      in chickens infected in ovo with JB, multiple fibrosarcomas arose in different
      organs a few days after birth, whereas no tumor could be detected in parallel
      experiments in either JN- or AEV Pst124-infected animals. These results
      demonstrate that in embryo fibroblast cells, v-jun and v-erbB can act
      synergistically to enhance the transformation potential of either oncogene alone
      both in vitro and in vivo.

PMID- 1975845
TI  - [Differential diagnosis of inguinal hernia and cryptorchism in children].

PMID- 1975847
TI  - [The immunology of trophoblast is a fascinating but unsolved problem].

PMID- 1975844
TI  - Biological and molecular variability of human immunodeficiency virus type 2
      isolates from The Gambia.
AB  - Seven new human immunodeficiency virus type 2 (HIV-2) isolates (CBL-20 to CBL-26)
      from The Gambia were characterized. Their cytopathogenicity and growth in vitro
      correlated with the severity of clinical disease. CBL-22 was highly sensitive to
      neutralization by HIV-2 sera and was cross-neutralized by some HIV-1 sera. These
      findings, the differing sizes of envelope glycoproteins of individual isolates,
      and the sequence analysis of amplified regions of the viral DNAs show that these
      HIV-2 isolates from one geographical region in West Africa exhibit biological and
      genome variability comparable to that observed for HIV-1.

PMID- 1975846
TI  - [Experience with the treatment of various allergic diseases using a new histamine
      and serotonin antagonist bicarphene].

PMID- 1975848
TI  - [Mosquito repellents containing DEET can affect the central nervous system].

PMID- 1975849
TI  - Potential value of serology for diagnosis of extrapulmonary tuberculosis.
AB  - The possible benefits for improved diagnosis of extrapulmonary tuberculosis were
      evaluated by means of a modified serological competition assay. Antibodies to the
      38 kD Mycobacterium tuberculosis antigen were detected in 73% of cases of
      extrapulmonary tuberculosis and 70% of smear-negative cases of pulmonary
      tuberculosis at a chosen specificity of 98%. Of 55 patients (45%) whose diagnosis
      of tuberculosis was not made until 7 days or longer after admission, 76% were
      positive for the antibody. In this group the serological test would have allowed
      chemotherapy to be started on average 12.5 days earlier and would have obviated
      the need for 80% of diagnostic biopsies.

PMID- 1975850
TI  - Detection of cytomegalovirus nucleic acid sequences in pancreas in type 2
      diabetes.
AB  - Nucleic acid sequences specific for human cytomegalovirus (CMV) were found in
      samples of pancreatic tissue from patients with non-insulin-dependent (type 2)
      diabetes mellitus. RNA extracted from paraffin-embedded or fresh-frozen specimens
      from 14 of 32 (44%) diabetic patients but from none of 49 non-diabetic controls
      reacted with 10 kb (pJN201) or 6.6 kb (pCM3) probes of human CMV immediate-early
      or late gene products, respectively. The RNA from the 32 diabetic patients did
      not react with nucleic acid probes for mumps, rubella, or coxsackie B viruses. In
      situ nucleic acid hybridisation on tissues from 5 randomly selected human-CMV
      positive patients showed that the human CMV signal was localised primarily in the
      islets of Langerhans and not in exocrine cells. Despite the clear viral nucleic
      acid signal in tissues of human-CMV-positive patients, there were no
      morphological injuries to the islets, no inflammatory cells in the islets, and no
      perivascular inflammatory cell cuffing. These findings suggest a possible
      association of human CMV with type 2 diabetes in human beings.

PMID- 1975851
TI  - Inhaled budesonide for treatment of recurrent wheezing in early childhood.
AB  - 77 children, aged 11 to 36 months (mean 24) with moderately severe recurrent
      wheezing, were treated with budesonide pressurised aerosol 400 micrograms twice
      daily or placebo for 12 weeks in a double-blind, parallel-group trial. Aerosols
      were inhaled from a spacer with a facemask. Budesonide significantly improved
      symptom scores of wheezing, sleep disturbance, and patient happiness. The
      frequency of severe exacerbations that required a course of oral prednisolone was
      also significantly reduced. The treatment effect appeared to be fully established
      after 6-8 weeks and no side-effects could be ascribed to the active treatment.
      The findings indicate that young children below 3 years of age can inhale a
      pressurised aerosol from a spacer with a facemask. Use of topically active
      glucocorticosteroids with this simple device may reduce symptoms and distress in
      young children with moderately severe recurrent wheeze and dyspnoea, and possibly
      reduce their requirement for oral steroids.

PMID- 1975852
TI  - Location of facioscapulohumeral muscular dystrophy gene on chromosome 4.
AB  - The autosomal dominant disorder facioscapulohumeral muscular dystrophy (FSHD) is
      the last of the major progressive muscular dystrophies in which the gene had not
      been located. In linkage analysis on ten Dutch families with this disorder a lod
      score of 6.34 at a recombination fraction of 0.13 was obtained with the
      microsatellite marker Mfd 22 (D4S171). This maps the FSHD gene to chromosome 4.
      Only one family was uninformative for this marker. We found no evidence of
      genetic heterogeneity.

PMID- 1975854
TI  - Nothing is unthinkable.

PMID- 1975853
TI  - Absence of close linkage between maternal genes for susceptibility to pre
      eclampsia/eclampsia and HLA DR beta.
AB  - To test the possibility that maternally expressed susceptibility genes for pre
      eclampsia/eclampsia are closely linked to the HLA region on chromosome 6 of the
      human genome, members of ten pedigrees with multiple cases of these disorders
      were typed for HLA DR beta restriction fragment length polymorphisms by means of
      TaqI digests. The data were analysed by the LIPED program to calculate lod
      scores, by several programs to detect potential heterogeneity of recombination
      fraction between pedigrees, and by the affected-sibling and the affected-pedigree
      member methods. The results exclude close linkage. If the putative susceptibility
      genes lie on chromosome 6 they must lie at least 5 centiMorgans, and probably
      more, from the HLA DR beta loci. No indication of linkage at higher recombination
      fractions was found. The main maternally expressed genes affecting susceptibility
      to pre-eclampsia are not in the HLA region.

PMID- 1975856
TI  - Ancestral odontology.

PMID- 1975855
TI  - Management of prolactinoma.

PMID- 1975857
TI  - Failure to thrive revisited.

PMID- 1975858
TI  - Red weals under the sun.

PMID- 1975859
TI  - Health is a sustainable state.

PMID- 1975860
TI  - Psychiatric findings in Wolfram syndrome homozygotes.
AB  - Diabetes mellitus and bilateral optic atrophy are the defining characteristics of
      the autosomal recessive Wolfram syndrome. Diabetes insipidus, neurogenic bladder,
      deafness, and other neurological manifestations are frequent. A review was made
      of the medical records of 68 Wolfram syndrome patients, aged between 8 and 43
      years, identified by casefinding throughout the USA. 41 of the patients (60%) had
      episodes of severe depression, psychosis, or organic brain syndrome, as well as
      impulsive verbal and physical aggression. These symptoms were very severe in 17
      patients (25%), of whom 12 required admission to a psychiatric hospital and 11
      attempted suicide. We conclude that the Wolfram syndrome gene predisposes
      homozygotes to psychiatric illness.

PMID- 1975861
TI  - Relative efficacy and safety of intravenous drugs for termination of sustained
      ventricular tachycardia.
AB  - The relative safety and efficacy of intravenous administration of adenosine,
      lignocaine, disopyramide, flecainide, and sotalol for termination of stable,
      induced ventricular tachycardia was assessed in serial trials. Ventricular
      tachycardia was terminated by pacing if it persisted 10-15 min after the end of
      drug administration. 24 patients with recurrent ventricular tachycardia were
      studied. Ventricular tachycardia was terminated by a drug in 35 of 105 trials. In
      6 patients no drug terminated the arrhythmia. Adenosine did not terminate
      tachycardia or have any serious adverse effect in any patient; both flecainide
      and disopyramide were significantly more effective than lignocaine, but
      flecainide had significantly more severe adverse effects than lignocaine.
      Lignocaine was the safest drug and should continue to be used as first-line drug
      therapy for stable ventricular tachycardia. Disopyramide should be considered as
      second-line treatment. DC cardioversion is necessary for unstable ventricular
      tachycardia, and its availability must be ensured before attempted
      pharmacological intervention.

PMID- 1975862
TI  - Recurrent miscarriage.
AB  - On epidemiological evidence, the definition of recurrent miscarriage should be
      three or more consecutive pregnancy losses. Data should be collected to 28 weeks'
      gestation but analysis up to 20-22 weeks' or 500 g fetal weight should also be
      possible. General practitioners and gynaecologists should do what they feel is
      suitable for couples whose history does not meet these criteria but a diagnosis
      of recurrent miscarriage should not be made. Women meeting the definition can be
      subdivided into primary and secondary groups, respectively consisting of those
      who have lost all previous pregnancies and those who have had one successful
      pregnancy followed by consecutive losses.

PMID- 1975863
TI  - Medicare marches on.

PMID- 1975864
TI  - Juices, coffee enemas, and cancer.

PMID- 1975865
TI  - Bristol Cancer Help Centre.

PMID- 1975866
TI  - The Scots and their hearts.

PMID- 1975867
TI  - Hyperosmolar glucose solution or prostaglandin-F2 alpha for ectopic pregnancy.

PMID- 1975868
TI  - Faecal incontinence resulting from alpha 1-adrenoceptor blockade.

PMID- 1975869
TI  - Spongiform encephalopathy in an Israeli born to immigrants from Libya.

PMID- 1975870
TI  - Polymerase chain reaction decontamination: the wipe test.

PMID- 1975871
TI  - Phenobarbitone and epilepsy.

PMID- 1975872
TI  - In-vitro production of cytokines in serum.

PMID- 1975874
TI  - Erythematous reactions at intramuscular injection sites.

PMID- 1975873
TI  - Multiparameter flow cytometric quantification of membrane proteins in long-term
      cryopreserved tissue blocks.

PMID- 1975875
TI  - SIDS, surfactant, and temperature.

PMID- 1975876
TI  - Birth of second twin.

PMID- 1975877
TI  - Cutaneous leishmaniasis after expedition to Panama.

PMID- 1975878
TI  - Controlled-release prostaglandin E2 pessary.

PMID- 1975879
TI  - High-dose intravenous immunoglobulin for multiple sclerosis.

PMID- 1975880
TI  - Detection of pathogenic Yersinia enterocolitica by the polymerase chain reaction.

PMID- 1975881
TI  - Retrospective analysis of breast histology and indication for surgical
      intervention.

PMID- 1975882
TI  - Polymorphic sulphoxidation of carbocisteine.

PMID- 1975883
TI  - Debrisoquine hydroxylation phenotyping: do we expect too much?

PMID- 1975884
TI  - HCV testing in low-risk population.

PMID- 1975885
TI  - Eosinophilia-myalgia syndrome associated with prescribed L-tryptophan.

PMID- 1975886
TI  - L-arginine-induced hypotension.

PMID- 1975887
TI  - Limitations of serum creatine kinase assay in diagnosis of acute myocardial
      infarction.

PMID- 1975888
TI  - Diagnosis of Enterocytozoon bieneusi microsporidiosis in AIDS patients by
      recovery of spores from faeces.

PMID- 1975889
TI  - Patients' acceptance of diathermy loop treatment.

PMID- 1975891
TI  - Seasonal affective disorder and season-dependent abnormalities of melatonin
      suppression by light.
AB  - Twelve patients with seasonal affective disorder (SAD) and eleven normal controls
      were exposed to 2000 lux and 300 lux of artificial full-spectrum light on
      consecutive nights during the winter. Suppression of melatonin secretion under
      the two light intensities was measured and the difference between their effects
      was taken as a measure of light sensitivity. The test was repeated in summer in
      both groups, when the SAD subjects were well. The SAD but not the normal group
      showed a significant seasonal variation in sensitivity to light. There was
      evidence of supersensitivity in the winter but also of subsensitivity to light in
      the summer.

PMID- 1975890
TI  - Renal effects of cadmium body burden of the general population.
AB  - In a cross-sectional population study to assess whether environmental exposure to
      cadmium is associated with renal dysfunction, 1699 subjects aged 20-80 years were
      studied as a random sample of four areas of Belgium with varying degrees of
      cadmium pollution. After standardisation for several possible confounding
      factors, five variables (urinary excretion of retinol-binding protein, N-acetyl
      beta-glucosaminidase, beta 2-microglobulin, aminoacids, and calcium) were
      significantly associated with the urinary excretion of cadmium (as a marker of
      cadmium body burden), suggesting the presence of tubular dysfunction. There was a
      10% probability of values of these variables being abnormal when cadmium
      excretion exceeded 2-4 micrograms/24 h. Excretion reached this threshold in 10%
      of non-smokers. There was also evidence that diabetic patients may be more
      susceptible to the toxic effect of cadmium on the renal proximal tubule.

PMID- 1975892
TI  - Hypocholesterolaemic factor from gallbladder cancer cells.
AB  - A patient is reported with drug-resistant familial hypercholesterolaemia in whom
      serum cholesterol fell after the onset of gallbladder cancer with intraperitoneal
      invasion. Cancer cells were obtained from ascitic fluid and a cultured cell line
      established. Incubation of the culture medium of these cells with skin
      fibroblasts from the patient and from normal subjects increased low-density
      lipoprotein (LDL) receptor activity in a dose-dependent manner. These results
      show that gallbladder cancer cells from this patient secrete a substance that
      stimulates LDL receptor activity. This substance may have contributed towards
      reduction of serum cholesterol.

PMID- 1975893
TI  - Prevention of relapses in Wegener's granulomatosis by treatment based on
      antineutrophil cytoplasmic antibody titre.
AB  - 58 patients with biopsy-proven Wegener's granulomatosis (WG) were prospectively
      screened for clinical evidence of the disease 3-monthly, with antineutrophil
      cytoplasmic antibody (ANCA) measurements every month. Over 24 months, ANCA rose
      in 20 patients, 9 of whom were randomly assigned to receive combined 9 and 3
      month courses of cyclophosphamide and prednisolone, respectively, at the time of
      ANCA rise; and 11 patients who were untreated except if there was a clinical
      relapse. 6 of 11 untreated patients relapsed within 3 months of ANCA rise. 3 of
      the remaining 5 patients relapsed after 3 months. There were no early or late
      relapses in patients randomised to treatment. Patients receiving no treatment at
      the time of ANCA rise took more cyclophosphamide and prednisolone than patients
      who were treated. Side-effects did not significantly differ between the two
      groups.

PMID- 1975895
TI  - Disease clustering: hide or seek?

PMID- 1975894
TI  - Preliminary report: effects of interleukin-1 on platelet counts.
AB  - Recombinant human interleukin-1 beta was given in 5 daily intravenous infusions
      to ten patients with metastatic malignant disorders as part of an antineoplastic
      trial. All ten patients experienced transient increases in heart rate, low-grade
      fevers, and rigors. A neutrophil-dominated 100% rise in leucocyte counts occurred
      4-8 h after treatment. Leucocyte counts returned to baseline levels within 24 h
      of interleukin-1 beta infusion. A 50% rise in platelets occurred in response to
      interleukin-1 beta; the increase in platelet counts was first noted 6 days after
      treatment began and was sustained for 24 days after treatment. Interleukin-1 beta
      may therefore be beneficial in the treatment of conditions of thrombocytopenia
      associated with haematological disorders and chemotherapy for malignant
      disorders.

PMID- 1975896
TI  - ACE inhibitors and tissue binding.

PMID- 1975897
TI  - Conscience and complicity.

PMID- 1975898
TI  - Boarding the train.

PMID- 1975899
TI  - Foodborne illness: an overview.

PMID- 1975900
TI  - High mortality among recipients of bought living-unrelated donor kidneys.
AB  - Between June, 1984, and May, 1988, 130 patients from three renal units in the
      United Arab Emirates and Oman went of their own accord to Bombay, where they
      bought, through brokers, kidneys from living unrelated Indian donors for US$2600
      3300. 131 transplants were done, and the 122 patients who survived the
      perioperative period returned to their original renal units for follow-up.
      Altogether there were 25 deaths (16 before the end of 3 months, 4 in the next 3
      months, and 4 more by the end of the first year), which gave a patient survival
      rate of 81.5% at 1 year. The patients who died had multiple complications, but
      infection was the commonest known cause of death. Patients were not properly
      instructed about their treatment, and little or no information was given to
      doctors following up the patients, criteria of suitability for transplantation
      were not strict, and patients were exposed to serious infections (including human
      immunodeficiency virus infection). In addition, the availability of living-donor
      programmes slows down attempts to establish cadaver-donor transplant programmes.

PMID- 1975901
TI  - Recurrent miscarriage. II: Clinical associations, causes, and management.
AB  - Firm evidence on the causes of recurrent miscarriage is scant. The true rate is
      probably artificially heightened by a reproductive compensation effect. The
      commonest direct cause is probably repeated sporadic chromosome abnormalities,
      which occur consecutively merely by chance. Congenital and acquired anatomical
      defects of the uterine fundus and cervix, parental chromosomal rearrangements,
      gene mutations, antibodies to cardiolipin, and luteal phase defects each make a
      small contribution. Other causes, such as polycystic ovaries and immune
      rejection, may play some part but the evidence is not clear. Psychological
      stress, subclinical infections, thyroid disorders, and diabetes mellitus are
      probably not relevant. Reassurance and clear statements about prognosis are
      important and psychological support must be offered throughout investigation and
      subsequent pregnancy. Much more rigorous scientific studies from which clearer
      conclusions can be drawn are vital for better understanding of this important
      clinical problem.

PMID- 1975903
TI  - Cancer, The Lancet, and the media.

PMID- 1975902
TI  - Lag between discovery and production of new vaccines for the developing world.
AB  - Communicable diseases represent a considerable burden in terms of suffering and
      costs. The decision to develop a new vaccine varies with perspectives. The public
      health perspective is influenced largely by cost-benefit ratios; the community
      perspective by a strong desire to alleviate suffering and disability from disease
      and from vaccine side-effects; and that of vaccine producers by demand,
      technological feasibility of development, and anticipated return on investment.
      Each of these perspectives is important. However, they often are mutually
      exclusive. From a humanitarian and epidemiological perspective, the most urgent
      needs related to communicable diseases are those of the poorest countries; in the
      industrialised world, with the exception of the vaccine for the acquired
      immunodeficiency syndrome (AIDS), public health priorities, evaluated in terms of
      the cost-benefit ratio, often differ from those of the market, which usually
      selects its priorities according to return on investment. The six vaccines used
      in the Expanded Programme of Immunisation (EPI) are offered cheaply through a
      highly efficient bidding system. It would have to be extended, under the same
      form or differently, to other vaccines, such as those for rabies, hepatitis B, or
      japanese encephalitis. For vaccines that are being developed, such as conjugated
      polysaccharide or acellular pertussis vaccines, it is difficult to foresee how
      these expensive vaccines can be distributed. The situation is even worse for
      vaccines to be developed specifically for the third world. To make these vaccines
      available to everyone there must be technology that enables producers to sharply
      reduce production costs, and a subsidy for research and development and
      production.

PMID- 1975904
TI  - USSR: theft of Chernobyl data.

PMID- 1975905
TI  - Secrecy and product liability litigation.

PMID- 1975906
TI  - Lifestyle changes and heart disease.

PMID- 1975907
TI  - Bacitracin-associated peptides and contaminated L-tryptophan.

PMID- 1975909
TI  - Drug donations to Sudan.

PMID- 1975908
TI  - Bristol Cancer Help Centre.

PMID- 1975910
TI  - Light therapy in patient with seasonal fatigue.

PMID- 1975912
TI  - Intermittent leg ischaemia during competition cycling.

PMID- 1975911
TI  - Precocious familial gout.

PMID- 1975913
TI  - Prenatal genetic diagnosis from maternal peripheral blood.

PMID- 1975914
TI  - Aztreonam-induced anaphylaxis.

PMID- 1975915
TI  - Lack of inhibitor to monoclonal-antibody purified FVIII concentrate.

PMID- 1975916
TI  - Who pays for UK medical research today?

PMID- 1975917
TI  - Mutations in medium chain acyl-CoA dehydrogenase deficiency.

PMID- 1975918
TI  - Mitochondrial function and parental sex effect in Huntington's disease.

PMID- 1975919
TI  - Heterogeneity in proximal spinal muscular atrophy.

PMID- 1975920
TI  - Post-kala-azar dermal leishmaniasis in the absence of active visceral
      leishmaniasis.

PMID- 1975922
TI  - Treatment of neutropenia associated with dyskeratosis congenita with granulocyte
      macrophage colony-stimulating factor.

PMID- 1975921
TI  - Non-specificity of anti-HCV test for seroepidemiological analysis.

PMID- 1975923
TI  - Impaired gastrointestinal motility in pulmonary transplantation.

PMID- 1975924
TI  - LCAT activity as a prognostic liver function test.

PMID- 1975925
TI  - Diazepam as a truth drug.

PMID- 1975926
TI  - Continuous anti-dsDNA antibody apheresis in systemic lupus erythematosus.

PMID- 1975927
TI  - Association between Graves' ophthalmopathy and smoking.

PMID- 1975928
TI  - Inhibitory potencies of UK-69 578 and thiorphan.

PMID- 1975929
TI  - Foscarnet and crystals in glomerular capillary lumens.

PMID- 1975930
TI  - Treatment of Helicobacter pylori positive duodenal ulcers.

PMID- 1975931
TI  - Acyclovir in late pregnancy to prevent neonatal herpes simplex.

PMID- 1975932
TI  - Antigens that modern vaccines must contain.

PMID- 1975934
TI  - White matter lesions of AIDS encephalomyelitis.

PMID- 1975935
TI  - International perspectives on HIV.

PMID- 1975933
TI  - Rapid test for distinguishing HIV-1 and HIV-2.

PMID- 1975936
TI  - Reconstitution of peripheral benzodiazepine receptor expression in X-linked
      chronic granulomatous disease by interferon-gamma.

PMID- 1975937
TI  - Norfloxacin resistant Neisseria gonorrhoeae in North America.

PMID- 1975938
TI  - Occult axillary lymph-node micrometastases in breast cancer.

PMID- 1975939
TI  - Finger clubbing and tumour necrosis factor alpha.

PMID- 1975940
TI  - ECMO and outcome of mechanical ventilation in infants of birthweight over 2 kg.

PMID- 1975941
TI  - Microvascular effects of bradykinin in the isolated perfused guinea-pig
      hindbrain: method and characterization of a possible third type of bradykinin
      receptor.
AB  - The method used by McGregor for the isolated mesenteric vascular bed was adapted
      to study the mechanisms of regulation of cerebral blood flow in the isolated
      perfused guinea-pig brain. This method allows the recording of the perfusion
      pressure in the hindbrain perfused at constant physiological flow, and has been
      successfully applied to the study of the effect of bradykinin. Bradykinin
      elicited a vasoconstriction that was independent of the presence of the
      endothelium. The pD2 ranged between 7.50 and 7.60, respectively, with and without
      the endothelium. Des-Arg9-BK was unable to elicit a vasoconstriction.
      [Tyr(Me)8]BK had a partial agonist activity. Both [Leu9]des-Arg10-KD and
      [DArg0,Hyp3,DPhe7]BK had similar antagonist activities. From these
      pharmacological characteristics, the receptor involved in this response seems to
      be different from a B1 or a B2 receptor.

PMID- 1975942
TI  - [New methods and new technics in pedodontics: "conscious sedation"!].
AB  - The reasons why is it sometimes necessary to resort in paediatric dentistry to
      the use of conscious sedation with N2O/O2 are explained together with clinical
      indications and applications. The excellent results obtained with this technique
      lead to greater cooperation of the child, to a positive emotional contact with
      dental treatment and the possibility of performing the necessary therapies with
      greater precision.

PMID- 1975943
TI  - [Flow cytometric quantitation of the proliferation associated nuclear antigen
      p105 and DNA content of advanced gastric cancers as a prognostic factor:
      preliminary report].

PMID- 1975944
TI  - Identification of a protein altered in mutants resistant to microtubule
      inhibitors as a member of the major heat shock protein (hsp70) family.
AB  - A major cellular protein (P2; approximately 70 kilodaltons) which is altered in
      Chinese hamster ovary (CHO) cell mutants resistant to the microtubule inhibitors
      colchicine and podophyllotoxin has been shown to correspond to the constitutive
      form of the 70-kilodalton heat shock protein (hsc70). The inference that P2 and
      hsc70 are the same protein is based on the following observations: (i) migration
      of P2 in two-dimensional polyacrylamide gels in the same position as that
      reported for hsc70; (ii) cross-reactivity of a monoclonal antibody which reacts
      with both the constitutive and induced forms of hsp70 with the P2 spot from wild
      type CHO cells and with both P2 and a mutant form of P2 in a CHO cell mutant;
      (iii) specific reactivity of a polyclonal antibody to P2 with both the
      constitutive and heat-induced forms of hsp70 in human cells; (iv) identical
      immunofluorescent staining of dot/patchlike structures with both P2 and hsp70
      antibodies in human and CHO cells; and (v) a cDNA clone for hsc70 has been
      isolated and sequenced from wild-type CHO cells. The in vitro transcription and
      translation product of this cDNA has been shown to comigrate with the P2 protein
      spot in two-dimensional gels, indicating their identity. The fact that there is
      an alteration in hsc70 in mutants resistant to antimitotic drugs suggests a role
      for this protein in the in vivo assembly and function of microtubules.

PMID- 1975946
TI  - [The detection of the sites of mediator release in a motor nerve ending].
AB  - A model of the postsynaptic current generation in response to a release of the
      quantum mediator from the nerve terminal is suggested. In its terms the law of
      the current density attenuation is determined as j = I/rb, where I is the current
      density in the site of generation, while j--current densities at the distance r
      from the site of generation. Experiments with extracellular recording have shown
      that coefficient b equals approximately 1. Assuming that sites of the quantum
      release and a site of the postsynaptic current generation are spatially
      identical, the new method is suggested to determine coordinates of the
      transmitter release sites in the motor nerve terminal. This method consists in
      the measuring of a uniquantal signal amplitude by three extracellular
      microelectrodes, arranged at a distance of 5-10 microns from each other. The
      construction of spatial pictures of the transmitter secretion on the basis of the
      analysis of several hundreds of signals in the cutaneous pectoris frog muscle has
      shown that release sites are organized in groups transversal to the nerve
      terminal. It is supposed that these groups of sites reflect the transmitter
      secretion in the active zones of the nerve ending. Advantages, shortcomings and
      errors of the method are shown.

PMID- 1975945
TI  - Molecular cloning and analysis of the scon-2 negative regulatory gene of
      Neurospora crassa.
AB  - The sulfur regulatory system of Neurospora crassa is composed of a group of
      highly regulated structural genes (e.g., the gene encoding arylsulfatase) that
      are under coordinate control of scon+ (sulfur controller) negative and cys-3+
      positive regulatory genes. In scon-1 (previously designated sconC) and scon-2
      mutants, there is constitutive expression of sulfur structural genes regardless
      of the sulfur level available to the cells. The scon-2+ gene was cloned by sib
      selection screening of a cosmid-based gene library. The screening was based on
      the use of chromate, a toxic sulfate analog, which is transported into scon-2
      cells grown on high sulfur but is not transported into cells that have regained
      normal sulfur regulation. Restriction fragment length polymorphism analysis was
      used to confirm that the cloned segment mapped to the proper chromosomal
      location. In wild-type cells, Northern (RNA) blot analysis showed that a 2.6
      kilobase scon-2+ transcript was present at a substantial level only under sulfur
      derepressing conditions. Kinetic analysis showed that scon-2+ mRNA content
      increased as the cells became sulfur starved. Further, scon-2+ RNA was detectable
      in a nuclear transcription assay only under derepressing conditions. In scon-1,
      the levels of scon-2+ mRNA were found to be constitutive. In the cys-3 regulatory
      mutant, there was a reduced level of scon-2+ transcript. cys-3+ and ars-1+ mRNAs
      were present under both derepressing and repressing conditions in the scon-2
      mutant. Repeat-induced point mutation-generated scon-2 mutants were identical in
      phenotype to the known mutant.

PMID- 1975947
TI  - [An analysis of mediator secretion in the active zone of the motor nerve ending].
AB  - The topography of transmitter release sites at the motor-nerve terminal of the
      cutaneous-pectoris frog muscle has been determined using three extracellular
      electrodes. It is shown that release sites are united in groups arranged
      transversally to the nerve endings and reflecting the transmitter release in the
      active zones (AZ) of the nerve terminal. The quantitative analysis of revealed
      groups has permitted concluding that the maximal level of secretion is at the
      centre of AZ, decreasing to the edge and aside from AZ. At the low extracellular
      Ca2+ concentration all the AZ take part in the spontaneous release process, while
      in the evoked one--only some of AZ. Advantages of the three-microelectrode method
      over the two-microelectrode one are analyzed. It is found that the transmitter
      secretion in spatially isolated AZ leads to the polymodality in uniquantal signal
      amplitude distribution at extracellular recording. The role of AZ in the
      transmitter release process is discussed.

PMID- 1975948
TI  - Giant subdural empyema in an infant. Sonographic observations.
AB  - A giant subdural empyema was found to be the cause of a large head in a two month
      old female child referred for cranial sonography. The sonographic features of the
      subdural empyema as illustrated by this case are: (1) The presence of an extra
      axial space occupying lesion with mass effect. (2) Its fluid nature with mobile
      echogenic debris within. (3) Its large extent from frontal to occipital region,
      and (4) Its thick medial echogenic wall. A total of 250 ml of pus was evacuated
      from the empyema and the child was doing well on follow up at four months of age.

PMID- 1975949
TI  - [Report on the activities of the Societies of Traumatologists and Orthopedists in
      September 1989].

PMID- 1975950
TI  - [An experimental validation of the endolymphatic administration of
      pharmacological preparations for stimulating intestinal peristalsis in emergency
      surgery on the abdominal cavity].
AB  - Experiments were conducted on 75 rabbits to study the efficacy of endolymphatic
      administration of aceclidine, obsidan, and cerucal for stimulation of the
      intestine in its experimental paresis. The stimulating effect of the
      pharmacological agents was found to be of a longer duration in endolymphatic that
      in intravenous administration. This allowed endolymphatic pharmacological
      stimulation of the intestine to be suggested for the use in abdominal surgery.

PMID- 1975951
TI  - [The effect of a peptide-containing extract of the right hemispheric cortex on
      the recovery of conditioned reflex activity and on the level of neuromediators in
      the brain structures of rats after a unilateral frontal lobectomy].
AB  - Experiments were conducted on 97 non-inbred [correction of unbred] male rats to
      study the effect of a peptide-containing extract of the cortex of the right
      hemisphere of donor rats, who underwent left lobectomy 9 days before the
      experiment, on restoration of conditioned reflexes of bilateral avoidance and
      level of neuromediators in the brain structures of recipient rats with a similar
      damage to the cerebral cortex. It is shown that the brain extract from the right
      hemisphere of operated on donors has a much higher effect on the restoration of
      reflexes. At the same time it was found that in left frontal lobectomy this
      extract produces a most manifest effect on monoamine metabolism in the structures
      of the right intact hemisphere. It is suggested that a directed effect may
      possibly be produced on the development of compensatory-restorative process in
      the central nervous system by endogenous substances of peptide origin which are
      isolated from brain structures actively contributing to the restoration of
      disturbed functions.

PMID- 1975952
TI  - New salicylate therapies for ulcerative colitis.
AB  - Since the development of sulfasalazine about a half century ago, the prognosis
      for patients with ulcerative colitis has improved significantly. Very recently,
      the active moiety of oral sulfasalazine, 5-aminosalicylic acid, has been made
      available as a topical (enema) preparation. In this article, Dr. Bruckstein
      reviews the advantages of the enemas in the treatment of ulcerative colitis and
      briefly examines the potential benefits of the new oral salicylate preparations.

PMID- 1975953
TI  - Effects of the peroxisome proliferator di(2-ethylhexyl)phthalate on enzymes in
      rat liver and on carcinogen-induced liver altered foci in comparison to the
      promoter phenobarbital.
AB  - The livers of rats given either the peroxisome proliferating hepatocarcinogen
      di(2-ethylhexyl)phthalate (DEHP) following initiation by 2-acetylaminofluorene
      (AAF) or the neoplasm promoter phenobarbital (PB) were studied for changes in 8
      histochemical properties. Male F344 rats were fed 200 ppm AAF for 7 weeks to
      induce hepatocellular altered foci, and were then fed diets containing either no
      chemical, 12,000 ppm DEHP or 500 ppm PB for 24 weeks. In hepatocytes, DEHP
      increased alkaline phosphatase activity throughout the lobule, but reduced gamma
      glutamyltransferase (GGT) activity in periportal hepatocytes. PB, in contrast,
      increased GGT activity in periportal hepatocytes. In foci that were induced by
      AAF, DEHP reduced the histochemical activity of GGT and did not increase the
      number, mean volume or volume % of foci detected by deficiencies in iron storage,
      glucose-6-phosphatase, adenosine triphosphatase or fibronectin. PB enhanced the
      expression of all 8 phenotypic abnormalities in foci such that either more
      profiles were detected or the area of foci was increased.

PMID- 1975954
TI  - Expression and activity of the POU transcription factor SCIP.
AB  - POU proteins have been shown to transcriptionally active cell-specific genes and
      to participate in the determination of cell fate. It is therefore thought that
      these proteins function in development through the stable activation of genes
      that define specific developmental pathways. Evidence is provided here for an
      alternative mode of action. The primary structure of SCIP, a POU protein
      expressed by developing Schwann cells of the peripheral nervous system, was
      deduced and SCIP activity was studied. Both in normal development and in response
      to nerve transection, SCIP expression was transiently activated only during the
      period of rapid cell division that separates the premyelinating and myelinating
      phases of Schwann cell differentiation. In cotransfection assays, SCIP acted as a
      transcriptional repressor of myelin-specific genes.

PMID- 1975957
TI  - Enhanced thrombolysis by a factor XIIIa inhibitor in a rabbit model of femoral
      artery thrombosis.
AB  - Factor XIIIa (FXIIIa) catalyzes covalent crosslinking reactions of fibrin,
      affording the clot additional structural stability and resistance to plasmin
      mediated degradation. Thus, inhibition of FXIIIa may render thrombi more
      susceptible to tissue-plasminogen activator (t-PA)-induced thrombolysis in vivo.
      We therefore examined thrombus weight and time to lysis in anesthetized rabbits
      undergoing arterial thrombosis produced by insertion of a copper coil into the
      lumen of the right femoral artery. The effects of t-PA alone (started 30 min
      after coil insertion) or in combination with a FXIIIa inhibitor (L722151) started
      15 min before, 8 min after or 20 min after coil insertion were determined.
      Although t-PA alone (2 mg/kg over 2 hrs) lowered thrombus weight significantly,
      there was no evidence of flow restoration. Addition of L722151 to t-PA before, or
      8 min after coil insertion, further lowered thrombus weights and produced
      thrombolysis in 50% of the animals. This beneficial effect was lost when L722151
      administration was delayed until 20 min after thrombus formation, suggesting that
      the type(s) of crosslinking inhibited by L722151 was complete by this time.
      Infusion of L722151 alone had no significant effect on thrombus weight. These
      results demonstrate a time-dependent facilitation of t-PA-induced arterial
      thrombolysis by FXIIIa inhibition in a small animal model.

PMID- 1975956
TI  - Evaluation of the pharmacological similarities between phenylpropanolamine and
      amphetamine: effects on schedule-controlled behavior.
AB  - In an effort to determine the degree to which the repeated administration of
      phenylpropanolamine (PPA) results in the development of tolerance to its
      disruptive effects on operant responding as well as cross-tolerance to the
      effects of acutely administered amphetamine, water-deprived rats were first
      trained on a fixed-ratio 5 (FR-5) schedule for water presentation. Dose-response
      curves for the effects of PPA and amphetamine (administered IP, 15 min
      presession) were then determined (ED50 = 35.0 and 2.6 mg/kg, respectively)
      followed by the chronic administration of 40.0 mg/kg PPA (administered IP, 15 min
      prior to each session). When responding returned to prechronic rates, the dose
      response curves were redetermined for both PPA (ED50 = 220 mg/kg) and amphetamine
      (ED50 = 4.8 mg/kg). In a second set of rats, trained under similar conditions, it
      was observed that pretreatment with alpha-methyltyrosine (AMT, 100 mg/kg IP, 2 h
      presession) antagonized the disruptive effects of both PPA and amphetamine,
      whereas pretreatment with reserpine (0.31 mg/kg, IP, 12 h presession) antagonized
      the disruptive effects of PPA, but exacerbated the disruptive effects of
      amphetamine. In a separate experiment, the repeated administration of PPA 100
      mg/kg or 200 mg/kg IP resulted in no long-lasting depletions of rat striatal
      dopamine, serotonin, or 3,4-dihydroxyphenylacetic acid (DOPAC) concentrations.
      These observations indicate that PPA and amphetamine share a similar mechanism of
      action to the degree that cross-tolerance develops, but which is nonetheless
      dissociable with respect to their differential sensitivity to antagonists and
      their neurotoxic efficacy.

PMID- 1975955
TI  - Cloning and expression of a rat brain GABA transporter.
AB  - A complementary DNA clone (designated GAT-1) encoding a transporter for the
      neurotransmitter gamma-aminobutyric acid (GABA) has been isolated from rat brain,
      and its functional properties have been examined in Xenopus oocytes. Oocytes
      injected with GAT-1 synthetic messenger RNA accumulated [3H]GABA to levels above
      control values. The transporter encoded by GAT-1 has a high affinity for GABA, is
      sodium-and chloride-dependent, and is pharmacologically similar to neuronal GABA
      transporters. The GAT-1 protein shares antigenic determinants with a native rat
      brain GABA transporter. The nucleotide sequence of GAT-1 predicts a protein of
      599 amino acids with a molecular weight of 67 kilodaltons. Hydropathy analysis of
      the deduced protein suggests multiple transmembrane regions, a feature shared by
      several cloned transporters; however, database searches indicate that GAT-1 is
      not homologous to any previously identified proteins. Therefore, GAT-1 appears to
      be a member of a previously uncharacterized family of transport molecules.

PMID- 1975958
TI  - Direct detection of the deletion-insertion polymorphism of the factor IX gene by
      analysis of amplified DNA sequences (PCR).

PMID- 1975959
TI  - Clinical relevance of immunocytochemical detection of multidrug-resistance
      associated P-glycoprotein in hematologic malignancies.
AB  - P-glycoprotein (P-170) is the phenotypic marker of tumoral cells that show the
      phenomenon of multidrug resistance (MDR). Using an immunocytochemical approach,
      we employed the monoclonal antibody C219 (which recognizes an epitope of such a
      glycoprotein) to evaluate in cytologic samples the expression of P-170 on
      neoplastic cells from 52 patients affected by different hematologic malignancies
      and its eventual correlation to clinical outcome. Longitudinal studies were also
      performed in 14 patients. Results obtained demonstrated that a) the so-called
      "MDR phenotype" may be heterogeneously represented (from less than 1 to 100% of
      positive cells) in hemopoietic tumors at diagnosis (without exposure to
      pharmacologic agents), as well as during the course of the disease, although a
      more substantial presence of P-170 occurred in treated patients. There was no
      correlation between neoplastic kinetic activity (such as expression of Ki 67
      recognized nuclear proliferation-associated antigen) and P-170-positive cells. b)
      Percentage of positive cells as well as intensity of staining seemed to be
      important in determining MDR; in general, there was a strong correlation between
      expression of P-170 in more than 20% of neoplastic cells and a lack of response
      to chemotherapy. However, some false-positive and false-negative cases were
      observed. c) The detection of scattered P-170-positive cells may predict a
      pharmacologic selection of intrinsic or mutant-resistant clones.

PMID- 1975960
TI  - [Primary treatment of traumatically dislocated teeth].
AB  - A case of successful replantation of a traumatically exarticulated tooth is
      presented. Avulsed teeth should be replanted immediately after the accident. If
      this is not possible, the periodontal tissue of the tooth should be protected
      from drying. Milk has been demonstrated to be a good medium in which the
      periodontal tissue can survive for as long as six hours whereas teeth stored in
      the buccal cavity must be replanted in the course of one, or at the latest two
      hours. Antibiotic treatment should be instituted immediately after replantation,
      and tetanus prophylaxis should be administered after the usual guidelines.
      Endodontic treatment should be performed after 10-14 days.

PMID- 1975961
TI  - [Neurotransmitters in Alzheimer's disease].
AB  - Alzheimer's disease is characterized by markedly reduced concentration of
      acetylcholine in hippocampus and neocortex, caused by degeneration of cholinergic
      neurons. Acetylcholine is essential in learning and memory. However, despite
      correlation between cholinergic defect and intellectual impairment in Alzheimer's
      disease, the effect of substitution therapy with cholinergics is very limited.
      Especially in younger Alzheimer patients, the degenerative process also affects
      other transmitter systems. Particularly the concentrations of serotonin,
      somatostatin and glutamate are significantly reduced. It is not elucidated how
      these transmitter defects contribute to symptomatology. The serotonin defect is
      thought to underlie the emotional and behavioural symptoms. The somatostatin
      defect is correlated to the reduced cerebral metabolism and thus might be a
      central phenomenon. The glutamate defect has been suggested to represent the
      neurochemical correlate to clinical dementia, because the activity in the
      hippocampal glutamatergic synapses is normally increased during learning.
      Therapeutically, the multiple transmitter defects imply that simple transmitter
      substitution can be expected to be of only limited value in Alzheimer's disease.

PMID- 1975962
TI  - [General practitioners' training in psychiatry and prescription of psychotropic
      drugs. 2. Attitudes of physicians to training in psychotherapy and the extent of
      their prescriptions].
AB  - The object of this investigation was to describe and analyse differences in
      psychiatric training and attitudes to and employment of psychotropic drugs among
      general practitioners with and without training in psychotherapy, respectively.
      The investigation was carried out as a multicentre questionnaire investigation in
      the County of Aarhus with participation of 192 out of 215 (89%) doctors who were
      invited. Thirty-nine of the participating general practitioners (20%) had
      participated in a supervised course in psychoanalytically orientated
      psychotherapy. Doctors who were trained in psychotherapy had more rarely had
      appointments in psychiatric departments than other doctors. Doctors trained in
      psychotherapy prescribed fewer benzodiazepines than other doctors (p less than
      0.05) and there was psychotherapy chose psychotherapy more frequently (p = 0.02)
      and more rarely tendency to a lower total prescription of psychotropic drugs.
      Doctors trained in a psychotropic drugs (p = 0.004) than doctors without this
      training as treatment for patients with psychosocial conflicts and they more
      rarely chose psychotropic drugs to supplement psychotherapy (p less than 0.0001).
      It is concluded that one of the ways of reducing the massive use of psychotropic
      drugs in Denmark is to improve general practitioners' training in psychotherapy.

PMID- 1975963
TI  - [Hemosorption and endolymphatic therapy in the treatment of paralytic ileus in
      peritonitis and acute intestinal obstruction].
AB  - Hemosorption and endolymphatic pharmacotherapy was included in the complex of
      treatment in 65 patients operated upon for spreaded forms of peritonitis and
      acute ileus. Hemosorption was performed within 12-24 h after operation,
      pharmacological agents (Aceclidine++, Cerucal, Obsidan) were introduced by
      antegrade endolymphatic infusions 4-6 h after hemosorption. The investigations
      have shown that in this case there rapidly appears intestinal peristalsis which
      is maintained not less than for 10-12 hours and in great part of patients it was
      completely recovered. Multiple stimulations by traditional methods were necessary
      in the control group to restore peristalsis. The combination of hemosorption and
      endolymphatic therapy may be recommended as an effective complex for the struggle
      against intestinal paresis in peritonitis and acute ileus in the postoperative
      period.

PMID- 1975965
TI  - [Current status of surgical treatment of mechanical jaundice of non-neoplastic
      etiology (VII All-Union Congress of Surgeons, Leningrad, October 18-20, 1989)].

PMID- 1975964
TI  - [Infection in abdominal surgery (review of reports of the VII All-Union Congress
      of Surgeons, Leningrad, October l8-20, 1989)].

PMID- 1975966
TI  - [A technical inhalation test variant for improving the effectiveness of the use
      of dose aerosols].
AB  - We compared the airway responsiveness to beta 2-agonist aerosol inhalation with
      two breathing techniques for bronchodilator testing in 25 patients with COPD.
      Open breathing technique showed better results than closed breathing technique.
      Causes for these results like optimization of volume and flow conditions for
      aerosol deposition are discussed.

PMID- 1975967
TI  - [The brain catecholamine systems in the regulation of dominance].
AB  - Effect was studied of catecholamine systems of the brain in the establishment of
      dominant-subordinate relations in artificial micropopulations formed of six
      males. Decrease of norepinephrine and dopamine content by the injection of alpha
      methyl-DL-tyrosine and decrease of norepinephrine alone by means of FLA-57 and
      also norepinephrine decrease and dopamine increase caused by combined injection
      of FLA-57 and alpha-DOPA were accompanied by a transfer of dominant and
      subdominant animals into the rank of subordinates. Changes of correlation between
      catecholamines probably had specific effect on zoosocial dominance of animals in
      micropopulation because changes were not found in the motor activity against the
      background of these preparations. Conclusion is made that brain catecholamines
      have a principle significance in dominance control.

PMID- 1975968
TI  - Loss of constitutional heterozygosity in chromosome 10 in human glioblastoma.
AB  - Gene deletion of chromosome 10 in 11 tumor tissues removed from nine patients
      with malignant glioma (seven glioblastomas and two malignant astrocytomas) was
      investigated. Loss of heterozygosity was found in four of the seven (57%) cases
      with glioblastoma, whereas heterozygosity was preserved in two malignant
      astrocytome cases. One glioblastoma case showed loss of heterozygosity only in
      the recurring tumor tissue, although heterozygosity was maintained in the initial
      tumor tissue. The significance of loss of heterozygosity in the growth and
      recurrence of glioblastoma is discussed.

PMID- 1975969
TI  - Cerebrospinal fluid levels of somatostatin, corticotropin-releasing hormone and
      corticotropin in alcoholism.
AB  - Reduced brain and cerebrospinal fluid (CSF) levels of somatostatin, corticotropin
      releasing hormone (CRH) and corticotropin (ACTH) have been reported among
      neuropsychiatric patients with cognitive dysfunction. Alcoholism is a disorder in
      which associated neuropsychiatric disorders occur. Therefore, we compared CSF
      levels of somatostatin, CRH and ACTH in alcoholics (n = 100) and normal controls
      (n = 30). There were no significant differences between the groups in
      concentrations of the 3 peptides. Moreover, there were no significant
      correlations between concentrations of the peptides in CSF and computed
      tomographic measures of the size of brain ventricles. There were, however,
      significant correlations between CSF concentrations of CRH and ACTH and between
      CSF concentrations of CRH and somatostatin in both the alcoholic and control
      groups.

PMID- 1975970
TI  - Leucocyte arylsulphatase A activity and subtypes of chronic schizophrenia.
AB  - Previous studies have suggested that arylsulphatase A (ASA - the biochemical
      marker of metachromatic leucodystrophy) deficiency may be present in a sizeable
      proportion of patients with chronic psychosis. This study surveyed leucocyte ASA
      activity in a group of chronic psychotic patients and compared ASA activity in 3
      subgroups fulfilling Research Diagnostic Criteria for schizophrenia
      (undifferentiated), paranoid schizophrenia and schizoaffective psychosis. Three
      of 45 patients had significantly reduced ASA activity but none had metachromatic
      leucodystrophy. Although ASA levels did not differ significantly between the
      groups, schizophrenics without a family history of schizophrenia had
      significantly lower ASA levels than those with. The implications of these
      findings are discussed.

PMID- 1975971
TI  - Medetomidine- and medetomidine-ketamine-induced immobilization in blue foxes
      (Alopex lagopus) and its reversal by atipamezole.
AB  - The sedative and immobilizing effects of the alpha 2-adrenoceptor agonist
      medetomidine alone or combined with the dissociative anesthetic ketamine, were
      studied in blue foxes. Medetomidine at doses of 25 and 50 micrograms/kg induced
      moderate to deep sedation, but only with the highest medetomidine dose tested,
      100 micrograms/kg, was the immobilization complete. Medetomidine 50 micrograms/kg
      combined with ketamine 2.5 mg/kg rapidly induced complete immobilization,
      characterized by good myorelaxation, and no clinically significant alterations in
      serially determined hematologic and serum chemistry parameters. The alpha 2
      adrenoceptor antagonist atipamezole effectively reversed the medetomidine- or
      medetomidine-ketamine-induced immobilizations. A transient increase in heart
      rates was noted after each atipamezole injection.

PMID- 1975972
TI  - Polypeptides induced in chick embryo cells by Kemerovo virus.
AB  - Fifteen polypeptides induced by Kemerovo virus were detected in chick embryo
      cells (Mr 140, 98, 89, 72, 65, 62, 57, 54, 50, 47, 43, 41, 39, 31 kD, and 30 kD).
      Nine of them, namely the 140, 98, 65, 62, 57, 54, 50, 47 kD, and 41 kD
      polypeptides were also found in the partially purified virus. However, the latter
      contained also considerable amount of host cell proteins, predominantly the 205
      kD, 45 kD, and 37 kD polypeptides. In the electron microscope the spherical viral
      particles exhibited a poorly defined surface structure of a diameter of 70-75 nm.

PMID- 1975973
TI  - Detection of viral DNA and activation of latent herpes simplex virus in the
      rabbit neural tissue.
AB  - Both trigeminal ganglia, brain stem, and cornea from rabbits with established
      latent herpes simplex virus type 1 (HSV-1) infection were examined by
      explantation and by spot blot hybridization using strain 17 Kpn I fragments i, d,
      and h and the DNA extracted from above mentioned tissues. Correlation between
      positive hybridization and reactivation of infectious virus in the cultured
      explants was documented by enhanced hybridization with the DNA extracts from
      explanted ganglion samples. In addition, we found positive hybridization in some
      noncultured ganglion and brain stem samples which did not yield infectious virus
      by explantation. Keeping in mind the pitfalls of false positive hybridization,
      the results may indicate during latency the presence in neural tissues of HSV DNA
      sequences which did not spontaneously reactivate in culture.

PMID- 1975974
TI  - Antibody against synthetic peptide derived from Epstein-Barr virus-determined
      nuclear antigen 1 (EBNA-1) in child non-Hodgkin's lymphoma.
AB  - Antibody reactivity against a synthetic peptide derived from Epstein-Barr virus
      nuclear antigen 1 (EBNA-1) was determined in 56 cases of child non-Hodgkin's
      lymphoma and 31 controls. The patients were divided into subgroups based on
      tumour location and histology and the antibody responses in the various groups
      were compared. A significant increase in both IgG and IgM antipeptide titres was
      detected in patients with tumours localized in the abdomen. High IgG titres were
      also noted in Burkitt-type, lymphoblastic, and centroblastic lymphomas. On the
      other hand, low or nil IgG titres were found in unclassified malignant lymphomas,
      in four cases of centroblastic-centrocytic lymphoma and in lymphomas located in
      the mediastinum. Surprisingly, the occurrence of antipeptide IgM antibody was
      highest in those tumours, where IgG titres were low, i.e. in subjects with
      mediastinal tumours and in unclassified malignant lymphomas. However, with the
      exception of tumours localized in the abdomen and unclassified tumours, the IgM
      titres in positive individuals were low and comparable with titres found in a
      part of healthy controls.

PMID- 1975975
TI  - Comparative assay of varicella skin test antigens by the ELISA and RPHA tests.
AB  - The antigenic potency of the varicella skin test antigens was assayed by reversed
      passive haemagglutination (RPHA) test using sheep red blood cells coated with
      zoster convalescent serum and by enzyme linked immunosorbent assay (ELISA) using
      anti-VZV sera or monoclonal antibody to gpI followed by an anti-IgG beta
      galactosidase conjugate. Three kinds of varicella skin test antigens were
      compared: a soluble varicella skin test antigen, a modified soluble varicella
      skin test antigen, and a crude varicella skin test antigen. The RPHA test was
      suitable for the soluble and for modified soluble varicella skin test antigens
      but it was not suitable for the crude varicella skin test antigen. ELISA was
      applicable for all the three antigen types. It was possible to assess
      quantitatively the content of viral antigens in the same type of the skin test
      antigen, but not by comparing the different skin test antigen types. ELISA was
      more efficient in the quantitative assay of the amount of viral antigens than the
      RPHA test.

PMID- 1975977
TI  - Neutralizing antibodies and serum interferon levels in the different stages of
      HIV infection.
AB  - The sera of patients infected with HIV were investigated for neutralizing
      antibodies (NA) and interferons. All samples from asymptomatic HIV carriers
      contained NA in high titres. In the sera of patients with AIDS related complex
      and AIDS the antibodies were found rarely and in lower titres. An early peak of
      acid-labile interferon (IFN)-alpha was observed in asymptomatic HIV-infected
      persons, and a late peak was found in AIDS patients. The data suggest that HIV NA
      may have beneficial effect in the asymptomatic phase. The presence of acid-labile
      IFN-alpha may indicate stimulation of IFN system by HIV-infected cells.

PMID- 1975976
TI  - Susceptibility of mammalian, avian, fish, and mosquito cell lines to rabies virus
      infection.
AB  - The relationship between plasma membrane receptor organization and cell
      susceptibility in vitro was investigated in mammalian, avian, fish, and arthropod
      cell lines infected with fixed rabies virus. IMR32, HeLa, CER, and EPC cells were
      widely susceptible to infection with CVS virus, whereas a lower level of specific
      viral antigens was detectable in A. albopictus cells. In spite of these
      differences, the amount of infectious virus particles bound to the various cell
      surfaces was similar. Competition experiments carried out with plasma membranes
      extracted from ability of these components to bind the virus and to prevent
      infection. The different cellular permissiveness to rabies infection described
      here did not correlate with significant differences in number or in chemical
      structure of the receptor binding sites, but more likely with events following
      virus adsorption.

PMID- 1975978
TI  - Properties in culture and persistence in cotton rats of the Rickettsia prowazekii
      vaccine strain E and its mutants.
AB  - Cultural properties and the capacity for persistence were studied in spontaneous
      erythromycin-resistant (E errSM), in induced erythromycin-resistant (E errI)
      mutants and in a virulent revertant (E Vir) of the vaccine strain E, as compared
      with parent vaccine strain E and standard virulent strain Breinl of Rickettsia
      prowazekii. Cultural properties of the strains were found to differ in passages
      in chick embryos (CE) and cultures of FL cells. Multiplication indices in CE of
      mutant E errI were significantly lower than those of other strains (E, E errSM, E
      Vir, Breinl). The multiplication rate in FL cells was found to be high in strains
      E errSM, Breinl, E Vir, being much lower in strains E errI and E. The capacity of
      the virulent revertant E Vir to persist in cotton rat (CR) was higher as compared
      with that of standard strain Breinl and significantly higher than that of the
      parent strain E. Low level carrier state of rickettsia was registered in CR
      infected with the mutant E errI.

PMID- 1975979
TI  - Heterogeneity of influenza B virus strains isolated in a local area of the
      disease during an influenza outbreak.
AB  - Ten strains of influenza B virus isolated in a local focus during an influenza
      outbreak were found to include 9 virus strain variants as demonstrated by
      different antigenicity of their haemagglutinin, ts-marker, sensitivity to heating
      at 56 degrees C/30 min, and to non-specific serum inhibitors. These strains
      induced antibodies in rats which interacted more actively with the virus isolated
      in earlier periods of this outbreak than with that isolated later. It might
      indicate that all strains originated from the same parent strain of virus, which
      induced the influenza outbreak in this area.

PMID- 1975980
TI  - The source of avian paramyxoviruses isolated during an outbreak of influenza
      among children.
AB  - In 1986 five avian paramyxovirus (PMV) strains were isolated in embryonated
      chicken eggs from sick children with influenza. The strains were identified as
      PMV-2 serotype due to the close antigenic relationships between their HN-proteins
      and of the reference PMV-2 strains isolated from different birds all over the
      world. No seroconversion to the isolates was found in the sick children, however,
      HI-antibodies were detected in hen's sera, eggs of which were used for the new
      strains isolation. The possible origin of isolated PMV-2 viruses is discussed.

PMID- 1975981
TI  - Bovine herpes mammalitis virus thymidine kinase gene.
AB  - Bovine herpes mammillitis virus (BHMV) codes for a thymidine kinase (Tk), the
      gene for which is located in a 2.6 kb SalI restriction endonuclease fragment with
      a map unit of 0.2-0.32. This particular DNA fragment can transfect LTk-mouse
      cells and convert them to Tk+. The gene position of BHMV Tk would suggest another
      homologous gene map position for BHMV and herpes simplex virus (HSV).

PMID- 1975982
TI  - Evidence of 5'-terminal modification in the kemerovo virus double-stranded RNA
      segments and its removal by treatment with alkaline phosphatase.
AB  - Only one strand of each double-stranded (ds) RNA segment of the Kemerovo virus
      genome was 5'end-labelled using gamma-32P-ATP and T 4 polynucleotide kinase after
      preceding dephosphorylation of 5'ends by calf intestinal alkaline phosphatase.
      This suggests a 5'-terminal modification of the one of complementary strands in
      the ds RNA segments.

PMID- 1975983
TI  - Comparison of skalica, Hypr, and Langat viruses by kinetic haemagglutination
      inhibition test.
AB  - The Skalica virus has been compared with Hypr and Langat viruses by kinetic
      haemagglutination-inhibition (HI) test. Using Hypr antigen, differences were
      observed between Skalica, Hypr, and Langat viruses. By the use of Skalica
      antigen, a close relationship between Hypr and Skalica viruses was detected,
      however, it was possible to differentiate the Langat virus. When Langat antigen
      was tested, a close relationship among all the three viruses was found.

PMID- 1975984
TI  - Percutaneous cholecystolithotomy with endoscopic lithotripsy by using a pulsed
      dye laser: preliminary experience.
AB  - Percutaneous cholecystolithotomy with endoscopically directed lithotripsy with a
      pulsed-dye laser was performed in eight patients for the treatment of symptomatic
      gallstones. All patients had stones that were not amenable to therapy by less
      invasive techniques. During the first stage of a two-stage procedure, a
      cholecystostomy catheter was placed percutaneously. During the second stage,
      performed at least 10 days later, the stones were fragmented with a laser and
      removed. Fragmentation of the stones was successful in all patients. In six
      patients, the gallbladder was completely cleared of stones, as assessed with
      endoscopy and cholecystography. In two patients, residual fragments remained in
      the gallbladder. No laser-related complications occurred. This preliminary
      experience suggests that the pulsed-dye laser is safe and effective in
      endoscopically directed lithotripsy of gallbladder stones.

PMID- 1975987
TI  - Thermogenic effect of thyroid hormones: interactions with epinephrine and
      insulin.
AB  - The interactions between thyroid hormones, epinephrine, and insulin in the
      regulation of energy expenditure were investigated in a group of healthy young
      men before and after thyroxine (T4) treatment (300 micrograms/day for 14 days) at
      basal plasma insulin concentrations and during hypoinsulinemia with and without
      epinephrine infusion (0.05 micrograms.kg fat-free mass-1.min-1). T4 treatment
      induced moderate hyperthyroidism and increased resting energy expenditure (RMR).
      The effect was more pronounced during short-term hypoinsulinemia, but
      hypoinsulinemia by itself did not influence RMR. Epinephrine infusion caused a
      significant increase in energy expenditure. The effect was most pronounced at
      hypoinsulinemia and with T4 treatment. Hypoinsulinemia and T4 treatment were not
      additive in their effects. We conclude that basal insulin concentrations mask
      some of the thermogenic effects of thyroid hormones and epinephrine. Thus insulin
      antagonism may suppress some of the thermogenic actions of thyroid hormones and
      epinephrine.

PMID- 1975985
TI  - Characterization of Epstein-Barr virus-induced lymphoproliferation derived from
      human peripheral blood mononuclear cells transferred to severe combined
      immunodeficient mice.
AB  - Mice with severe combined immunodeficiency (SCID) received 6 X 10(7) fresh human
      peripheral blood mononuclear cells (PBMC) intraperitoneally from Epstein-Barr
      virus (EBV)-seropositive and -seronegative donors. B95-8 EBV was inoculated
      intraperitoneally and intravenously to the mice 6 weeks after transfer of
      seronegative PBMC. Three of four mice transferred with PBMC from two EBV
      seropositive donors and two of four mice from two EBV-seronegative donors
      inoculated with EBV developed fatal EBV-induced lymphoproliferative disease
      within 6 to 10 weeks. These tumors were oligoclonal or polyclonal by cytoplasmic
      immunoglobulin expression. Furthermore no consistent clonal chromosomal
      abnormalities were shown. Cell lines established from these tumors showed low
      cloning efficiency in soft agarose. In addition, latent membrane protein, B
      lymphocyte activation antigen (CD23), and cell-adhesion molecules (ICAM-1, CD18)
      all were expressed in the EBV-positive infiltrating lymphoproliferative lesions
      in each mouse. These results suggest that lymphoid tumors are comparable to
      lymphoblastoid cell lines immortalized by EBV and are not malignant lymphomas
      such as Burkitt's lymphoma. This model may be useful for investigating mechanisms
      responsible for the growing numbers of lymphoproliferative diseases that are
      occurring in patients with inherited or acquired immunodeficiencies.

PMID- 1975986
TI  - Clonal analysis of solitary follicular nodules in the thyroid.
AB  - Accumulated data using functional, morphologic, and histochemical analysis
      suggests that follicular proliferations in the thyroid include polyclonal and
      monoclonal patterns with encapsulated follicular adenomas most frequently
      monoclonal, and other nodules generally polyclonal. However, examples of
      polyclonal carcinomas or adenomas raise the possibility that histologically
      similar lesions may arise through different pathogenetic mechanisms. The authors
      have performed a clonal analysis of histologically benign and malignant thyroid
      nodules in seven women using HPRT (hypoxanthine phosphoribosyl transferase) and
      PGK (phosphoglycerate kinase) restriction fragment length polymorphisms (RFLPs)
      on the X chromosome. These RFLPs used in concert with methylation-sensitive
      restriction endonucleases HpaII and HhaI permit distinction of active and
      inactive X chromosomes. DNA from a multinodular goiter showed equal sensitivity
      of both X chromosome RFLP alleles to a methylation-sensitive restriction
      endonuclease, consistent with a polyclonal origin. In contrast, three solitary
      follicular nodules and three carcinomas displayed predominant sensitivity of a
      single RFLP allele, consistent with a monoclonal origin. Although further
      detailed studies will be necessary to understand polyclonal origins reported for
      some adenomas, our data from a limited number of samples supports a predominantly
      monoclonal origin, and possible neoplastic pathogenesis, for many solitary
      adenomatous nodules in the thyroid.

PMID- 1975988
TI  - Systemic pH modifies ketone body production rates and lipolysis in humans.
AB  - To investigate whether changes in systemic pH influence ketone body production or
      utilization, total ketone body (TK) kinetics were measured with [3
      14C]acetoacetate and D-beta-[1,3-13C2]hydroxybutyrate tracers in overnight fasted
      subjects during metabolic alkalosis (NaHCO3 infusion) or acidosis [NH4Cl
      ingestion or arginine (Arg)-HCl infusion]. Somatostatin, with insulin, glucagon,
      and growth hormone replacement, was infused in all studies. Blood pH and HCO3-
      (mM) increased from baseline (0-30 min) to 180-210 min by 0.08 +/- 0.02 and 7 +/-
      1 with NaHCO3 and decreased by 0.08 +/- 0.2 and 7 +/- 1 or 5 +/- 1 with NH4Cl or
      Arg-HCl (all P less than 0.005). Over this period blood TK (microM) differed
      between the NaHCO3 (+198 +/- 65) and both NH4Cl (-90 +/- 53) and Arg-HCl (-154 +/
      55) (P less than 0.05). These changes resulted from parallel alterations in TK
      production rate of appearance (Ra TK, mumol.kg-1.min-1), because changes from
      baseline in Ra 14C TK also differed between NaHCO3 (+1.9 +/- 0.8) and NH4Cl (-1.0
      +/- 0.6) and Arg-HCl (-2.0 +/- 0.5) (P less than 0.05). Ra TK calculated with
      single- or dual-tracer techniques were similar. Blood free fatty acids (FFA)
      increased with NaHCO3, and FFA and glycerol decreased with NH4Cl and Arg-HCl,
      suggesting that FFA availability mediated the pH effects on hepatic ketogenesis.
      These results demonstrate that modest changes in systemic pH modify FFA
      availability and TK production rates.

PMID- 1975990
TI  - Volume-sensitive synaptic input to neurons in guinea pig inferior mesenteric
      ganglion.
AB  - The relationship between changes in intracolonic volume related to propulsive
      contractions and synaptic potentials recorded intracellularly in neurons in the
      inferior mesenteric ganglion (IMG) was investigated in vitro. Distension of the
      colon induced propulsive contractions (frequency, 2-5/min), which reduced
      intracolonic volume by 88%. Each propulsive contraction was sustained for 10-12
      s, after which time the colon refilled. The sustained propulsive contractions
      were associated with a decrease in the amplitude and frequency of fast
      cholinergic excitatory postsynaptic potentials (EPSPs) and partial repolarization
      of the slow EPSP. The pressure-volume relationships of the colonic segments had
      two limbs: at distension pressures less than 15 cmH2O ("volume limb") the
      intracolonic volume was proportional to the distension pressure; greater than 15
      cmH2O ("pressure limb") the intracolonic volume did not increase further. The
      changes in synaptic input were related to these pressure-volume relationships. In
      the volume limb, the frequency and amplitude of fast EPSPs were proportional to
      intracolonic volume and maximized with volume. In the pressure limb, there was a
      slow depolarization of the membrane that increased with greater distension
      pressures. Under isovolumic conditions, the changes in intraluminal pressure
      associated with colonic contractions were not associated with changes in
      excitatory synaptic input to IMG neurons. These experiments demonstrate that
      colonic mechanoreceptors to IMG neurons are sensitive to both intracolonic volume
      and pressure.

PMID- 1975989
TI  - Renal arginine synthesis: studies in vitro and in vivo.
AB  - Renal arginine synthesis is a major endogenous source of arginine.
      Argininosuccinate lyase occurs almost exclusively in kidney cortex. In studies
      with isolated renal cortical tubules, we observed rapid rates of arginine
      synthesis from citrulline, provided a source of the N atom of the guanidino group
      of arginine was supplied. Aspartate, glutamate, or glutamine were effective,
      whereas glycine, alanine, serine, or NH4Cl were ineffective as this second
      substrate. Arginine synthesis as a function of citrulline concentration was
      determined and was found to be highly sensitive to citrulline concentrations in
      the physiological range (60 microM), suggesting that renal arginine synthesis in
      vivo could be regulated by circulating citrulline levels. Therefore, arginine
      synthesis by the kidney was investigated in vivo by measuring the net flux of
      citrulline and arginine in saline-infused (control group) and citrulline-infused
      rats. In normal animals, uptake of citrulline was 60.5 +/- 20.7 nmol.min-1.100 g
      body wt-1, and a similar arginine release was observed. Citrulline infusion that
      increased circulating citrulline levels fourfold resulted in a similar increase
      in renal citrulline uptake (224 +/- 33 nmol.min-1.100 g-1) and a similar increase
      in renal production of arginine. The results suggest that the availability of
      citrulline is a limiting factor for renal arginine synthesis in rats.

PMID- 1975991
TI  - Exclusion of the tyrosine hydroxylase gene in 14 panic disorder pedigrees.

PMID- 1975992
TI  - Violent behavior among schizophrenic patients.

PMID- 1975993
TI  - [H2-receptor antagonists in obstetrical-gynecological anesthesiological work].

PMID- 1975994
TI  - Vecuronium and McArdle's disease.

PMID- 1975995
TI  - Esmolol reduces autonomic hypersensitivity and length of seizures induced by
      electroconvulsive therapy.
AB  - We evaluated the clinical effectiveness of esmolol, an ultra-short-acting beta 1
      adrenergic receptor blocking drug, to control the sinus tachycardia and increase
      in arterial blood pressures induced by electroconvulsive therapy (ECT). Each of
      20 patients, ASA physical status I-III, participated in a double-blind,
      randomized study, involving four match-pair trials (placebo versus esmolol)
      during ECT. Each patient acted as his or her own control (total number of ECT
      procedures, 160). We administered a 4-min infusion of either placebo or esmolol
      at the rate of 500 micrograms.kg-1.min-1. We then induced anesthesia with
      methohexital and succinylcholine. After administration of electrical stimulation
      for ECT, the rate of infusion decreased to 300 micrograms.kg-1.min-1 for three
      additional minutes and was then discontinued. Statistically significant
      reductions in mean heart rate from minute 2 until minute 15 and in maximum heart
      rate (the mean of each patient's maximum heart rate after seizure changed from
      152 +/- 23 to 115 +/- 24 beats/min) occurred in patients given esmolol. During
      and immediately after infusion, arterial blood pressure also decreased. Finally,
      the length of seizures decreased, as manifested clinically from 48 +/- 18 to 39
      +/- 14 s and on electroencephalogram from 86 +/- 41 to 67 +/- 28 s. We conclude
      that esmolol effectively controls the hyperdynamic response to ECT and reduces
      the length of seizures. The significance of the latter to the overall
      effectiveness of ECT is not known.

PMID- 1975996
TI  - Prolongation of postoperative epidural sufentanil analgesia with epinephrine.

PMID- 1975997
TI  - Pitfalls associated with epidural opiates.

PMID- 1975998
TI  - [Pre-ischemic protection of the myocardium with glutamic acid during heart valve
      prosthesis under artificial circulation].

PMID- 1975999
TI  - [The cost of postoperative drug analgesia of patients with cancer].
AB  - Calculation of expenses on drug analgesia based on 1687 case records of cancer
      patients with different tumour location (lung, esophageal, gastric, rectal,
      uterine and breast cancer) has revealed different structure of expenditure on
      days 1 to 3 of the postoperative period. On the day of surgery, 44% on average
      were spent on narcotic analgesics and 37% on analgin, on the 2nd and 3rd days
      postoperatively the ratio was 31 and 35% and 25 and 28% respectively, which to a
      certain extent indicates changes in postoperative pain intensity in cancer
      patients. The expenses on narcotic analgesics and analgin during those days were
      31 and 68% of the total sum, respectively, which in absolute figures was 1 rouble
      4 kopecks per patient on average. Estimation of expenses on drug analgesia in
      cancer patients during the first 3 days after radical surgery make it possible
      for the physicians to better understand the proportions of such expenditures in
      the budget of medical institutions.

PMID- 1976000
TI  - [Regional analgesia after intrathoracic surgery].

PMID- 1976001
TI  - [Intrathecal and epidural administration of alpha adrenergic receptor agonists].
AB  - Alpha-agonists are frequently added to local anaesthetic agents to prolong the
      duration of spinal or extradural anaesthesia. Adrenaline and phenylephrine have
      been employed most commonly for this purpose. Recent controlled studies indicated
      that the alpha-adrenoceptor agonist clonidine, when administered spinally, has a
      dose-dependent antinociceptive effect. Clonidine seems to be as effective as
      adrenaline to prolong the duration of local anaesthetic blocks and is useful to
      decrease the incidence of tourniquet pain under spinal anaesthesia. As they
      improve the intensity and duration of opioid analgesia, intraspinal alpha
      agonists have also a synergic analgesic effect with spinal opioids. Alpha-agonist
      effects are due: 1) to an activation of the post and/or presynaptic alpha 2
      adrenoceptors in the substantia gelatinosa of the spinal cord, 2) to a local
      vasoconstriction by stimulating vascular smooth muscle alpha-receptors which
      decrease the rate of absorption of local anaesthetics from the subarachnoid or
      extradural space, 3) to a co-activation of the spinal opioid and alpha-adrenergic
      receptors at the spinal cord level. However, spinally administered alpha-agonists
      have side effects, which include vasoconstriction in the spinal cord,
      hypotension, bradycardia or tachycardia, somnolence and respiratory depression.
      To minimize such complications, great care may be needed, which is described in
      this review, assessing the minimal required amount of alpha-agonists and
      effective clinical monitoring. The development of this technique in the
      management of subarachnoid and extradural anaesthesia and of chronic pain is
      discussed.

PMID- 1976002
TI  - [Biological bases of puberty].

PMID- 1976003
TI  - [Continuous subcutaneous infusion of beta 2-agonists in infantile asthma].
AB  - Five infants aged 7 to 17 months were treated for asthma with a continuous
      subcutaneous infusion of a beta 2-agonist for 6 to 11 days in a dosage of 0.1
      microgram/kg/mn. The patients had a severe attack of asthma with problems with
      infusions and/or problems with nebulizations of beta 2-agonists and/or bronchial
      stasis. No local or systemic adverse effects were recorded. This mode of
      administration of beta 2-agonists proved extremely useful, either as single
      therapy or as part of a therapeutic protocol including antibiotics, steroids and
      theophylline. It avoids the problems met with administration of beta 2-agonists
      by the other routes and allows the child freedom of movement. The main indication
      is the severe attack of asthma that fails to respond to nebulizations. We suggest
      this new therapeutic method should be included in the therapeutic armamentarium
      for infantile asthma, although its exact place and indications need to be further
      defined by studies in a larger number of patients.

PMID- 1976004
TI  - Auditing community screening for undescended testes.
AB  - Different ways of auditing screening for undescended testes, using Hospital
      Activity Analysis data, hospital case notes, and community/general practice
      records are described. The cumulative orchidopexy rate per 1000 male births in
      successive birth cohorts is a simple tool for monitoring trends within a health
      district. Information gained from community/general practice records is valuable
      in highlighting problem areas in screening, such as the lack of clear diagnostic
      criteria and referral pathways.

PMID- 1976005
TI  - Cholangitis associated with cholecystitis in patients with acquired
      immunodeficiency syndrome.
AB  - Four patients with acquired immunodeficiency syndrome developed severe abdominal
      pain and fever due to acute acalculous cholecystitis. In all patients,
      preoperative laboratory data showed elevation of alkaline phosphatase and gamma
      glutamyltransferase levels. Endoscopic or intraoperative cholangiography showed
      signs of intrahepatic and extrahepatic cholangitis. Cholecystectomy was performed
      and prompt relief of symptoms was achieved in all patients; no postoperative
      complication was observed. One patient did not develop any recurrence during an
      18-month period of follow-up; two patients died 2 and 3 months after the
      operation. One patient developed recurrent abdominal pain and cholestasis 4
      months after the operation, with dilatation of the common bile duct and papillary
      stenosis due to progression of cholangitis. These observations suggest that
      cholangitis is frequently associated with cholecystitis in patients with the
      acquired immunodeficiency syndrome. Its pathogenesis is not known.

PMID- 1976006
TI  - Multiple endocrine neoplasia.

PMID- 1976008
TI  - [Modification of the neurotoxin RTX-III from the sea anemone Radianthus
      macrodactylus].
AB  - The influence of chemical modification on neurotoxin RTX-III toxicity in mice has
      been studied. The toxicity was not affected by modification of Trp30 residue with
      2-hydroxy-5-nitrobenzyl bromide but was diminished by a factor of 100 after
      reduction of the toxin's two disulfide bonds with 2-mercaptoethanol followed by
      derivatization with iodoacetamide. Blocking carboxyl groups with [3H]glycine
      methyl ester in the presence of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide led
      to only a two-fold drop in toxicity in the case of monocarboxylate-modified
      derivatives and a six-fold decrease for dimodified derivatives. A conception of
      multipoint attachment of the toxin to sodium channel is discussed.

PMID- 1976007
TI  - A 15N-n.m.r. study of cerebral, hepatic and renal nitrogen metabolism in
      hyperammonaemic rats.
AB  - 1. Rats were infused with 15NH4+ or L-[15N]alanine to induce hyperammonaemia, a
      potential cause of hepatic encephalopathy. HClO4 extracts of freeze-clamped
      brain, liver and kidney were analysed by 15N-n.m.r. spectroscopy in combination
      with biochemical assays to investigate the effects of hyperammonaemia on tissue
      concentrations of ammonia, glutamine, glutamate and urea. 2. 15NH4+ infusion
      resulted in a 36-fold increase in the concentration of blood ammonia. Cerebral
      glutamine concentration increased, with 15NH4+ incorporated predominantly into
      the gamma-nitrogen atom of glutamine. Incorporation into glutamate was very low.
      Cerebral ammonia concentration increased 5-10-fold. The results suggest that the
      capacity of glutamine synthetase for ammonia detoxification was saturated. 3.
      Pretreatment with the glutamine synthetase inhibitor L-methionine DL-sulphoximine
      resulted in 84% inhibition of [gamma-15N]glutamine synthesis, but incorporation
      of 15N into other metabolites was not observed. The result suggests that no major
      alternative pathway for ammonia detoxification, other than glutamine synthetase,
      exists in rat brain. 4. In the liver 15NH4+ was incorporated into urea,
      glutamine, glutamate and alanine. The specific activity of 15N was higher in the
      gamma-nitrogen atom of glutamine than in urea. A similar pattern was observed
      when [15N]alanine was infused. The results are discussed in terms of the near
      equilibrium states of the reactions involved in glutamate and alanine formation,
      heterogeneous distribution in the liver lobules of the enzymes involved in
      ammonia removal and their different affinities for ammonia. 5. Synthesis of
      glutamine, glutamate and hippurate de novo was observed in kidney. Hippurate, as
      well as 15NH4+, was contributed by co-extracted urine. 6. The potential utility
      and limitations of 15N n.m.r. for studies of mammalian metabolism in vivo are
      discussed.

PMID- 1976009
TI  - [Anaerobic gram-negative bacilli].

PMID- 1976010
TI  - Repeated amphetamine and fencamfamine: sensitization and reciprocal cross
      sensitization.
AB  - The repeated administration of amphetamine and related dopamine agonists results
      in an augmented or sensitized behavioral response to subsequent administration of
      these drugs. In addition to reflecting central nervous system plasticity, this
      altered response profile may also represent an animal model for stimulant-induced
      psychosis in humans. Therefore, considerable interest has been focused on
      determining the mechanisms underlying the sensitization process. One approach
      involves comparing and contrasting the effects of various stimulants possessing
      different molecular mechanisms of action. In this regard, some evidence suggests
      that fencamfamine and amphetamine interact with pharmacologically distinguishable
      dopamine pools. Therefore, we compared the behavioral response profiles to the
      repeated administration of behaviorally comparable doses of amphetamine and
      fencamfamine, and examined the pattern of cross-interaction between the two
      stimulants. Fencamfamine produced an amphetamine-like pattern of behavioral
      augmentation, and both drugs exhibited identical patterns of cross-sensitization.
      These results lend further support to the sensitization model of stimulant
      psychosis. Possible dopaminergic mechanisms underlying the sensitization are
      discussed.

PMID- 1976011
TI  - Human liver aminopeptidase M and its regulation by bile acids.

PMID- 1976012
TI  - Regulation of mouse T cell associated serine proteinase-1 (MTSP-1) by proteinase
      inhibitors and sulfated polysaccharides.
AB  - Mouse T cell associated serine proteinase-1 (MTSP-1) is expressed by activated T
      cells in vitro and in vivo, stored in cytoplasmic granules and secreted upon
      their specific restimulation. The aim of this study was to identify those
      structures which may control proteolysis by MTSP-1 in vivo in the vascular and
      extravascular systems. Here we show, that MTSP-1 was effectively inhibited by
      vascular and extravascular serpins such as antithrombin III and Cl-esterase
      inhibitor, as well as by aprotinin and alpha 2-macroglobulin. On the other hand,
      interaction of MTSP-1 with sulfated glycosaminoglycans, i.e., heparin and
      chondroitin sulfate, led to increased enzymatic activity and an altered fine
      specificity of MTSP-1 for peptide substrates. These results suggest that the
      level of MTSP-1 activity as well as its specificity can be regulated by
      constituents of the extracellular environments.

PMID- 1976013
TI  - Studies on the metabolism of glycolyl-CoA.
AB  - Glycolyl-CoA can be formed during the course of the beta-oxidation by rat liver
      mitochondria of 4-hydroxybutyrate. The existence of this beta-oxidation has been
      previously supported by the occurrence of 4-hydroxybutyrate and its beta
      oxidation catabolites in urine from patients with 4-hydroxybutyric aciduria, an
      inborn error of gamma-aminobutyric acid metabolism due to the deficiency of
      succinic semialdehyde dehydrogenase. The characteristics of the mitochondrial
      beta-oxidation of 4-hydroxybutyrate were, in rat liver, compared with those of
      the mitochondrial beta-oxidation of butyrate. The inhibition by malonate of the
      oxidation of 4-hydroxybutyrate was about twofold weaker than that of oxidation of
      butyrate, whereas both oxidations were abolished by preincubating the
      mitochondria with 1 mM valproic acid, a known inhibitor of mitochondrial beta
      oxidation. Mitochondria from rat kidney cortex were demonstrated to catalyse, as
      previously shown for hepatic mitochondria, the carnitine-dependent oxidation of
      12-hydroxylauroyl-CoA-omega-Hydroxymonocarboxylyl-CoAs are thus concluded to be
      precursors of glycolyl-CoA also in rat kidney cortex. In addition, 3
      hydroxypyruvate was found to be a precursor of glycolyl-CoA, since it was
      oxidized by bovine heart pyruvate dehydrogenase with a cofactor requirement
      similar to that of pyruvate oxidation. Glycolyl-CoA was a substrate of carnitine
      acetyltransferase (pigeon breast muscle). Pig heart citrate synthase was capable
      of catalyzing the condensation of glycolyl-CoA with oxaloacetate. The product of
      this reaction induced low NADH production rates dependent on the addition of
      porcine heart aconitase and isocitrate dehydrogenase.

PMID- 1976014
TI  - Mechanisms generating the time course of dual component excitatory synaptic
      currents recorded in hippocampal slices.
AB  - We studied with the whole-cell recording techniques, the mechanisms underlying
      the time course of the slow N-methyl-D-aspartate (NMDA), and fast non-NMDA
      receptor-mediated excitatory postsynaptic currents (EPSCs) in hippocampal slices.
      The rising phase of the NMDA receptor-mediated component of the EPSC as well as
      the decaying phase of the NMDA and non-NMDA component were highly temperature
      sensitive, suggesting that neither of these processes is determined by free
      diffusion of transmitter. Moreover, glutamate uptake blockers enhanced the
      responses to exogenously applied glutamate, but had no effect on the decay of
      either the NMDA or non-NMDA components of the EPSCs. On the other hand, open
      channel blockers known to modify NMDA channel kinetics reduced the EPSC decay
      time. Thus, the present results support a model in which the rise time and decay
      of the NMDA component are determined primarily by slow channel kinetics and the
      decay of the non-NMDA component is due either to channel kinetics or to
      desensitization.

PMID- 1976016
TI  - Large-scale collection of circulating haematopoietic progenitors in cancer
      patients treated with high-dose cyclophosphamide and recombinant human GM-CSF.
AB  - Circulating haematopoietic progenitors from 36 cancer patients were collected by
      continuous-flow leukapheresis during the phase of rapid haematopoietic recovery
      after pancytopenia induced by high-dose cyclophosphamide and then cryopreserved
      for autologous transplantation. 20 of the patients also received intravenous
      infusion of recombinant human granulocyte macrophage-colony stimulating factor
      (rhGM-CSF) for 7, 10 or 14 days after cyclophosphamide. 106 leukapheresis
      procedures were done for 2-5 consecutive days. Leukapheresis was started
      significantly earlier in patients receiving rhGM-CSF. In these patients, yields
      of peripheral blood elements (leucocytes, mononuclear cells, haematopoietic
      progenitors and platelets) were significantly higher than in controls treated
      with cyclophosphamide only. In particular, the mean number of granulocyte
      monocyte colony-forming cells was 43.88 X 10(4) vs. 6.16 X 10(4) per kg patient
      body weight per leukapheresis. Side-effects of leukapheresis were limited to
      central venous catheter occlusion and fever in 4% and 2% of all procedures,
      respectively.

PMID- 1976017
TI  - (R)- and (S)-5-hydroxy-2-(dipropylamino)tetralin (5-OH DPAT): assessment of
      optical purities and dopaminergic activities.
AB  - Racemic 5-hydroxy-2-(dipropylamino)tetralin (5-OH DPAT), a potent and selective
      dopamine (DA) D2-receptor agonist, was resolved into the enantiomers by a new
      method. The enantiomers of 5-OH DPAT were determined by chiral ion-pair
      chromatography using N-benzyloxycarbonylglycyl-L-proline as the counter ion. The
      enantiomeric purity of (R)-5-OH DPAT was found to be greater than 99.7%. The
      ability of the enantiomers to change the rat brain DOPA levels was evaluated in
      vivo. The results indicate that (R)-5-OH DPAT is a weakly potent DA D2-receptor
      antagonist.

PMID- 1976015
TI  - Long-term increase of glutamate decarboxylase mRNA in a rat model of temporal
      lobe epilepsy.
AB  - Behavioral changes following injury, neural degeneration, and aging partly
      reflect the synaptic plasticity of the nervous system. Such long-term plastic
      changes are likely to depend on alterations in the production of proteins
      involved in synaptic structures and neurotransmission. We have studied the
      regulation of the mRNA encoding one such protein, glutamate decarboxylase (GAD),
      the rate limiting enzyme of GABA synthesis, after a unilateral lesion in the
      hippocampus that leads to increased seizure susceptibility. Quantitative in situ
      hybridization reveals a long-term increase in GAD mRNA in several bilateral
      structures, as well as in specific neurons in the ipsilateral dentate gyrus. Our
      data do not support the often stated hypothesis that seizure susceptibility
      depends on the malfunction of GABA neurons.

PMID- 1976018
TI  - Third Regional Conference on Dracunculiasis in Africa.

PMID- 1976019
TI  - Radioligand binding characteristics of beta 2-adrenoceptors of cultured melanoma
      cells.
AB  - The existence of beta-adrenoceptors on intact cells of the human malignant
      melanoma cell line A-375 was investigated using the binding properties of the
      tritiated radioligand (-)-[3H]CGP-12177, a hydrophilic non-selective beta
      adrenoceptor antagonist. Displacement experiments of the radioligand from its
      binding site were performed with antagonists and agonists to determine the beta
      adrenoceptor subtype selectivity. The binding of (-)-[3H]CGP-12177 was saturable,
      of high affinity (KD = 0.025 nmol/l, n = 12) and was rapid and readily
      reversible. The maximal number of binding sites (Bmax) was 33.5 +/- 1.9
      fmol/10(7) cells or 2018 +/- 114 receptors per cell. beta-adrenoceptor
      antagonists inhibited binding of the radioligand with monophasic displacement
      curves. IC50 values were (nmol/l): propranolol (non-selective) 2.82, alprenolol
      (non-selective) 2.0, ICI 118,551 (beta 2-selective) 3.5 and bisoprolol (beta 1
      selective) 2200. Agonists inhibited binding in the order of potency of
      isoprenaline greater than adrenaline greater than noradrenaline. It is concluded
      that cells of the melanoma cell line A-375 contain a homogeneous population of
      beta 2-adrenoceptors.

PMID- 1976020
TI  - Cross-linking and proteolysis in Ca2(+)-treated lens homogenates.
AB  - It was previously shown (Lorand et al. (1985) Biochemistry 24, 1525) that
      treatment of lens homogenate with Ca2+ produces two sets of changes which are
      catalyzed by intrinsic enzymes of the lens and which can be readily seen by
      alterations in the sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      profiles of proteins. With the aid of differential inhibitors of the two
      reactions (e.g., dansylcadaverine and leupeptin) it was possible to distinguish
      the transglutaminase-dependent cross-linking of proteins from the proteolytic
      degradative phenomena. We have now shown that the proteins which are affected by
      the two processes can be compartmentalized differentially by centrifuging the
      lens homogenate after exposure to Ca2+. The dimeric and oligomeric beta
      crystallin products of transglutaminase-mediated cross-linking are most clearly
      visible in the soluble supernatant, whereas the proteolytically susceptible
      proteins--possibly structural in nature, including vimentin--are predominantly
      present in the pellet. We have found a compound, 2-[3
      (diallylamino)propionyl]benzothiophene, which, by virtue of acting as a
      noncompetitive inhibitor of transglutaminase as well as of calpains I and II,
      effectively blocked both the cross-linking seen in the supernatant and the
      proteolysis seen in the pellet fraction, though perhaps with somewhat different
      sensitivities.

PMID- 1976021
TI  - The induction of adipose conversion by bezafibrate in 3T3-L1 cells. Synergism
      with dibutyryl-cAMP.
AB  - The induction of adipose conversion in 3T3-L1 cells by bezafibrate (Brandes, R.,
      Hertz, R. Arad R., Naishtat S., Weil, S. and Bar-Tana, J. (1987) Life Sci., 40,
      935-941) was enhanced by dibutyryl-cAMP as well as forskolin, theophylline or
      isobutylmethylxanthine added to the incubation medium together with the
      bezafibrate inducer. The synergistic effect of bezafibrate and dibutyryl-cAMP
      resulted in enhancing the expression of late markers of adipose conversion, e.g.,
      lipid accumulation or glycerol-3-phosphate dehydrogenase activity and its mRNA.
      This enhanced expression of late markers was reflected in shortening the time
      period required for their first appearance as well as increasing their yield
      during the course of adipose conversion. By following the accumulation of
      glutamine synthetase mRNA serving as an early marker for adipose conversion, the
      synergistic effect of bezafibrate and dibutyryl-cAMP was already evident as early
      as 5 h following their addition to confluent 3T3-L1 cells. Hence, the induction
      of adipose conversion by bezafibrate in 3T3-L1 cells appears to involve an early
      event which is rate-limited by the availability of intracellular cAMP.

PMID- 1976022
TI  - Relation of the CD11/CD18 family of leukocyte antigens to the transient
      neutropenia caused by chemoattractants.
AB  - Adherence of leukocytes to the endothelium is a prerequisite for infiltration and
      accumulation of cells at an inflammatory site. Recent studies suggest that the
      CD11/CD18 family of adhesion-promoting receptors plays a crucial role in the
      initial adherence of polymorphonuclear leukocytes (PMNs) to endothelium. We have
      studied the effect of the anti-CD18 monoclonal antibody (MoAb) IB4, on movement
      of PMN in rabbits. Accumulation of PMNs in the skin induced by a local injection
      of the chemoattractant, zymosan-activated serum (ZAS), was strongly inhibited, in
      a dose-dependent fashion, by intravenous injection of IB4. A greater than 95%
      reduction in PMN accumulation was seen with 1 mg IB4/kg body weight, the highest
      dose used. PMN-dependent plasma leakage in the ZAS-injected skin sites was also
      inhibited by pretreatment with MoAb IB4, with a similar dose dependence.
      Histamine-induced plasma leakage, which is PMN independent, was not affected by
      this treatment. F(ab)2 fragments of IB4 were as effective as the whole
      immunoglobulin G molecule in reducing PMN accumulation. The half-life of
      circulating IB4 in rabbits was found to be 11.5 hours. These results are
      consistent with in vitro studies that show that binding of PMNs to endothelium
      requires both expression of CD11/CD18 molecules and activation of the PMNs by
      agonists, and confirm that sites on CD11/CD18 that recognize endothelial cells
      are blocked by IB4. Other investigators have shown that injection of
      chemoattractants into the blood stream causes a rapid neutropenia associated with
      accumulation of PMNs in the lung. We find that intravenous treatment of animals
      with IB4 did not block the transient accumulation of PMNs in the lung induced by
      formyl-methionyl-leucyl-phenylalanine, suggesting that this accumulation occurs
      by a mechanism that does not require CD11/CD18 molecules.

PMID- 1976023
TI  - Right-left asymmetry of tyrosine hydroxylase in rat median eminence: influence of
      arterial baroreflex nerves.
AB  - Arterial baroreceptor nerves consist of 2 pairs of nerves, carotid sinus and
      aortic. The latter nerves differ bilaterally as to size and origin suggesting
      that central baroreceptor activity could be asymmetrical. This was tested by
      studying activity of tyrosine hydroxylase (TH), the rate limiting enzyme for
      catecholamine synthesis, on right and left sides of the brain in median eminence
      (ME), arcuate nucleus (ARCN), paraventricular nucleus (PVN) and supraoptic
      nucleus (SON). Seven days after right or left sinoaortic denervation (SAD),
      bilateral SAD or sham-operation (SO), in situ TH activity was determined by the
      rate of dihydroxyphenylalanine (DOPA) accumulation following administration of a
      dopa decarboxylase inhibitor. Unexpectedly, the intact, SO rats had significantly
      lower DOPA concentrations on the left than right sides of ME in two separate
      studies; right-left differences averaged 24% and 38%. Evidence supporting
      asymmetry of TH activity was the lower concentrations of catecholamines on left
      than right sides of the brain in intact SO rats, namely, dopamine in ME and ARCN
      and norepinephrine and epinephrine in ARCN. Unilateral and bilateral SAD further
      suppressed TH activity on the left side of the ME; the maximum right-left
      difference was 58% in rats with right SAD. Their ARCN also showed asymmetry of TH
      activity. Asymmetry of TH activity was attributable to asymmetry of TH protein
      which was significantly lower on the left sides of ME and ARCN. This is the first
      demonstration of bilateral asymmetry of TH in mediobasal hypothalamus and its
      enhancement by interruption of left or right afferents from the arterial vascular
      system.

PMID- 1976025
TI  - Effects of enucleation on postnatal development of catecholamines and serotonin
      metabolism in the superior colliculus of the rat.
AB  - We have measured the level of catecholamines and serotonin and their principal
      metabolites, and the activities of tyrosine hydroxylase, tryptophan hydroxylase
      and monoamine oxidase-A and -B in the rat superior colliculus during postnatal
      development after bilateral removal of the eyes. The visual deprivation has
      different effects on the catecholamines and serotonin metabolism. The major
      changes in both amines were at day 15. Tyrosine hydroxylase and tryptophan
      hydroxylase activities increased during postnatal development but this increase
      was higher in enucleated compared with controls. An increase of the MAO-B to MAO
      A ratio during postnatal development was found. The significance of these changes
      has been discussed.

PMID- 1976024
TI  - Neuropeptide content and connectivity of the rat claustrum.
AB  - The rat claustrum has a homogeneous distribution of the neuropeptides
      somatostatin (SOM), cholecystokinin (CCK) and vasoactive intestinal polypeptide
      (VIP) along its rostrocaudal axis. In general, neuropeptide levels are comparable
      to those of overlying pyriform cortex. Visualization of mRNA encoding SOM, CCK
      and VIP in cell bodies of the claustrum by in situ hybridization histochemistry
      demonstrates that all 3 neuropeptides are contained in intrinsic claustral
      neurons. Mid-coronal section of the claustrum itself, or interruption of
      potential rostral, caudal or medial connections between the claustrum and the
      rest of the brain did not significantly alter levels of VIP, SOM or CCK in
      claustrum, cerebral cortex, or basal ganglia. Isolation of the claustrum from the
      cerebral cortex immediately dorsal to it along its rostrocaudal aspect caused no
      change in peptide levels in claustrum indicating that VIP, SOM and CCK
      projections to claustrum do not arrive from dorsal cortical areas. Transection of
      the external capsule above the claustrum caused a 50-100% elevation of all 3
      peptides on the contralateral side of the lesion, suggesting that VIP, SOM and
      CCK synthesis and/or release within the claustrum may be regulated by projections
      from the contralateral side. VIP, SOM and CCK are candidates for
      neurotransmitters contained in neurons whose cell bodies are within the claustrum
      and possibly also immediately overlying lateral neocortex, and have their
      terminals mainly within the claustrum itself.

PMID- 1976026
TI  - Two types of quisqualate receptors are decreased in human olivopontocerebellar
      atrophy cerebellar cortex.
AB  - We used receptor autoradiography to study the distribution of ionotropic and
      metabotropic quisqualate (QA) receptors in normal human cerebellar cortex and
      cerebellar cortex from 7 cases of olivopontocerebellar atrophy (OPCA). In normal
      human cerebellar cortex, both types of QA receptors were densest in the molecular
      layer. Both ionotropic and metabotropic QA receptors were significantly
      diminished in the molecular layer of OPCA specimens. These results suggest that
      both ionotropic and metabotropic QA receptors are localized on Purkinje cell
      dendrites.

PMID- 1976027
TI  - Fetal brain transplants induce recovery of male sexual behavior in medial
      preoptic area-lesioned rats.
AB  - Male rats received bilateral lesions within the medial preoptic area which
      completely abolished sexual behavior. Hypothalamic fetal brain transplants
      gradually restored sexual behavior to prelesion levels by the 6th week after the
      transplant. Immunocytochemical analyses revealed tyrosine hydroxylase
      immunoreactivity neurons within the transplanted tissue. These results
      demonstrate that fetal brain transplants can restore an innate complex behavior
      in which no spontaneous recovery is observed.

PMID- 1976028
TI  - The role of glutamate in opiate descending inhibition of nociceptive spinal
      reflexes.
AB  - The present experiment examined descending inhibition of the nociceptive tail
      flick reflex produced by microinjection of morphine and glutamate into the
      periaqueductal gray (PAG) matter and the neurotransmitters mediating the
      inhibition at the level of the nucleus raphe magnus (NRM). The longlasting opiate
      analgesia was significantly reduced by microinjection of excitatory amino acid
      antagonists 1-(p-chlorobenzoyl)-piperazine-2,3-dicarboxylate (PCB, 3.25 mumol) or
      DL-2-amino-5-phosphono-valerate (APV, 25.38 mumol) into the NRM, whereas the
      short-lived glutamate analgesia was not. This indicates that although both opiate
      and non-opiate analgesia may originate in the PAG, the former is relayed through
      the NRM, whereas the latter is relayed by additional or different nuclei in the
      medulla. Two observations shed light on the question which receptors mediate the
      above effect in the NRM. First, PCB blocked morphine analgesia at doses that were
      8 times lower than doses of APV that were effective. Second, analgesia produced
      by injection of glutamate into the NRM was antagonized by PCB (3.25 mumol),
      whereas APV (25.38 mumol) failed to do so. Together these results indicate that
      kainate/quisqualate, but not N-methyl-D-aspartate (NMDA), receptors are
      implicated in the NRM as a relay station in opiate descending inhibition.

PMID- 1976029
TI  - Local enkephalins tonically modulate dopamine release in the striatum: a
      microdialysis study.
AB  - Kelatorphan, an inhibitor of the enkephalin-degrading enzymes, infused by
      microdialysis (10(-6) M) in the striatum of anaesthetized rats, significantly
      increased dopamine (DA) output but left dihydroxyphenylacetic acid and
      homovanillic acid extracellular levels unchanged. The local application of
      naltrexone (10(-6) M) prevented the effect of kelatorphan on DA release. These
      data indicate that local enkephalins tonically modulate DA release in rat
      striatum.

PMID- 1976030
TI  - Nerve stimulation in vivo acutely increases tyrosine hydroxylase activity in the
      superior cervical ganglion and its end organs.
AB  - Previous studies have shown that preganglionic nerve stimulation in vitro
      increases acutely the activity of tyrosine hydroxylase (TH), the rate-limiting
      enzyme in catecholamine biosynthesis, in sympathetic neuronal cell bodies in the
      rat superior cervical ganglion (SCG). In the present study, we have examined
      whether a similar increase occurs after nerve stimulation in vivo, and whether
      this enzyme activity also increases in sympathetic nerve terminals in autonomic
      end organs. Immediately following stimulation at 10 Hz for 15 min in vivo, TH
      activity was found to have increased 4- to 8-fold in the SCG and in 3 of its end
      organs: the iris, the pineal gland and the submaxillary gland. These results
      indicate that increases in sympathetic nerve activity in vivo can lead to
      increases in TH activity both in adrenergic cell bodies/dendrites in the SCG and
      in adrenergic nerve terminals/fibers in various autonomic end organs.

PMID- 1976031
TI  - Morphine and dynorphin(1-13) microinjected into the medial preoptic area and
      nucleus accumbens: effects on sexual behavior in male rats.
AB  - The effects on sexual behavior of opiate receptor stimulation within A10 and A14
      terminal areas were examined in the following experiments. Morphine (0.01-6 nmol)
      and dynorphin(1-13) (0.01-3 pmol) were microinjected into the medial preoptic
      area (MPOA). Morphine (10-100 pmol) and dynorphin (10-100 fmol) injected into the
      MPOA reduced both the latency to ejaculate and the number of intromissions
      triggering ejaculation. Morphine (6 nmol) produced a failure to resume copulating
      following the second ejaculation. Morphine (1-10 nmol) injected into the nucleus
      accumbens (ACC) shortened the latency to the first intromission and lengthened
      the second postejaculatory interval. Naloxone (3 mg/kg i.p.) reversed the effects
      of morphine on intromission latency and attenuated the lowering of ejaculatory
      threshold.

PMID- 1976032
TI  - Studies of the HER-2/neu proto-oncogene in human breast cancer.

PMID- 1976033
TI  - Detection of P-glycoprotein in human tumours.

PMID- 1976034
TI  - Concepts in the management of congestive heart failure.
AB  - "In the realm of congestive heart failure, we've made tremendous diagnostic and
      therapeutic strides--yet so many crucial questions remain unanswered. An
      educational meeting such as this can help us share what we know and progress to
      new awareness."

PMID- 1976035
TI  - Pharmacology of modalities of treatment.
AB  - "Diagnosing congestive heart failure and establishing the etiology are necessary
      first steps. Perhaps more critical, however, are assessing the severity of heart
      failure, prognosticating, and initiating pharmacotherapy."

PMID- 1976036
TI  - Goals of treatment and current management strategies.
AB  - "Many of us were taught in medical school that monotherapy is better than
      polypharmacy. But congestive heart failure (CHF) is a prototypical disease in
      which combination therapy including digoxin appears to surpass any of the agents
      used alone. In CHF we treat different aspects of the pathophysiology."

PMID- 1976037
TI  - Bite wound infections of the lower extremity.
AB  - Animal bite wounds of the lower extremity are considered high-risk wounds for
      infection, especially in the medically compromised individual. Management should
      be aggressive. Copious irrigation and debridement of the wound clearly proves to
      be of greater value in the prevention of infection than the indiscriminate use of
      so-called "prophylactic" antibiotic agents. Frankly infected wounds must also be
      managed aggressively, incorporating the use of antibiotics to eradicate the
      infection. Empiric use of an agent containing clavulanic acid or sulbactam is
      suggested until results are obtained from the bacterial culture and sensitivity.
      Tetanus prophylaxis should be considered for every bite wound, whereas rabies
      prophylaxis is warranted in selected cases.

PMID- 1976038
TI  - Two chromosomal locations for human ornithine decarboxylase gene sequences and
      elevated expression in colorectal neoplasia.
AB  - The polyamines are known to be essential for cellular proliferation. Ornithine
      decarboxylase (ODC) is a rate-limiting enzyme in the synthesis of these amines,
      and activity is elevated in colorectal tumors and polyps. Two ODC genes
      (designated ODC1 and ODC2) were localized by somatic cell hybridization and in
      situ techniques to 2p25 and 7q31-qter, respectively. Investigation of the
      expression of ODC in colorectal neoplasia reveals a consistent increase in mRNA
      expression compared with normal adjacent mucosa and control mucosa, ranging from
      1.3- to 12.2-fold. No amplification of the loci was seen. Comparison of ODC mRNA
      expression with ODC activity from the same samples revealed no direct
      correlation, suggesting that regulation of ODC in this system occurs at the
      posttranscriptional level.

PMID- 1976039
TI  - Genetic origin of a trophoblastic choriocarcinoma.
AB  - Gestational choriocarcinoma can follow a term birth, a nonmolar abortion, or a
      complete hydatidiform mole. Among hydatidiform moles, heterozygous ones resulting
      from fertilization of an egg devoid of a nucleus by a diploid sperm (XY) or by
      dispermy (XX or XY) have been suggested to carry an increased predisposition to
      transformation to choriocarcinoma. Data on genetic analysis of choriocarcinoma
      are meager, being limited to cytogenetic analysis of a handful of established
      cell lines. Although the majority of these were heterozygous, antecedent
      pregnancies or molar tissues have not been investigated in any of them to clearly
      establish their genetic origin. We present here the results of a study of
      chromosomal heteromorphisms and DNA restriction fragment length polymorphisms in
      a choriocarcinoma, the host, her spouse, and her son from the antecedent
      pregnancy. Our data show that the choriocarcinoma in this case most probably
      arose from the product of the same fertilization that led to the antecedent
      pregnancy.

PMID- 1976040
TI  - Steroid receptors, transcription factors, and gene expression. AACR special
      conference in cancer research.

PMID- 1976041
TI  - What determines the choice of treatment in patients with supraventricular
      tachycardia?
AB  - I have outlined the approach to therapy of supraventricular tachyarrhythmias
      practiced by a cardiologist who is not performing special studies in the cardiac
      electrophysiology laboratory. This review includes the list of common and rare
      supraventricular arrhythmias, application of diagnostic noninvasive procedures,
      indications for referral for special electrophysiologic studies, and brief
      description of drugs and procedures used in the therapy of supraventricular
      tachyarrhythmias. In addition to general guidelines for treatment of these
      arrhythmias, I have outlined specific recommendations for patients with acute
      myocardial infarction, angina pectoris, ventricular dysfunction and congestive
      heart failure, obstructive cardiomyopathy, hyperthyroidism, AV accessory
      pathways, chronic obstructive lung disease, diabetes mellitus, hypertension,
      concomitant ventricular arrhythmias, tachycardia-bradycardia syndrome, and
      anxiety.

PMID- 1976042
TI  - Morphological effects of somatostatin on rat somatotrophs previously activated by
      growth hormone-releasing factor.
AB  - Correlative morphological and physiological analysis was carried out in order to
      clarify the role of somatostatin in the inhibition of the secretion of growth
      hormone (GH) from somatotrophs of the rat anterior pituitary gland in vivo.
      Transmission electron microscopy combined with immunogold labelling showed an
      increased number of exocytotic GH-containing secretory granules in somatotrophs
      fixed between 2 and 10 min after injection of GH-releasing factor (GRF).
      Injection of GRF also induced the appearance of immunopositive material in
      cisternae of the Golgi apparatus, many coated vesicles and multivesicular bodies.
      Microtubules were observed more frequently throughout the cytoplasm, particularly
      in and near the Golgi region. At 2 and 10 min after injection of somatostatin
      (SRIF), both the number of exocytotic figures in the somatotrophs previously
      stimulated by GRF and the amount of radioimmunoassayable GH in the plasma were
      clearly decreased. Undulation of the plasma membrane (PM) induced by GRF rapidly
      disappeared, and the number of granules just beneath the plasma membrane was
      significantly reduced. After injection of SRIF, parallel bundles of
      microfilaments were often observed in the space between the granules and the
      plasma membrane. SRIF did not cause a noticeable decrease in the amount of
      immunopositive material, coated vesicles and multivesicular bodies in the Golgi
      areas or any significant changes in the distribution of microtubules. SRIF
      therefore appears to inhibit hormone release mainly at the level of the plasma
      membrane, probably through changes in the distribution of microfilaments.

PMID- 1976043
TI  - Some parasympathetic neurons in the guinea-pig heart express aspects of the
      catecholaminergic phenotype in vivo.
AB  - In a histochemical study of intrinsic cardiac ganglia of the guinea-pig in whole
      mount preparations, it was found that some 70-80% of the neurons express aspects
      of the catecholaminergic phenotype. These neurons have an uptake mechanism for L
      DOPA, and contain the enzymes for converting L-DOPA (but not D-DOPA) to dopamine
      and noradrenaline, i.e. aromatic L-aminoacid decarboxylase and dopamine beta
      hydroxylase. Monoamine oxidase is also present within some of the neurons. In
      these respects, the neurons resemble noradrenergic neurons of sympathetic
      ganglia, so we refer to them as intrinsic cardiac amine-handling neurons.
      However, these neurons do not contain tyrosine hydroxylase and show little or no
      histochemically detectable uptake of alpha-methyldopa, dopamine or noradrenaline,
      even after depletion of endogenous stores of amines by pre-treatment with
      reserpine. Noradrenergic fibres from the sympathetic chain form pericellular
      baskets around nerve cell bodies. The uptake of L-DOPA into nerve cell bodies is
      not prevented by treatment with 6-hydroxydopamine sufficient to cause transmitter
      depletion or degeneration of the extrinsic noradrenergic fibres. Such
      degeneration experiments suggest that axons of the amine-handling neurons project
      to cardiac muscle, blood vessels and other intrinsic neurons. The cardiac neurons
      do not show any immunohistochemically detectable serotonergic characteristics;
      there is no evidence for uptake of the precursors L-tryptophan and 5
      hydroxytryptophan or 5-HT itself, whereas the extrinsic noradrenergic nerve
      fibres within the ganglia can take up 5-HT when it is applied in high
      concentrations.

PMID- 1976044
TI  - The specificities of Sex combs reduced and Antennapedia are defined by a distinct
      portion of each protein that includes the homeodomain.
AB  - The sequence requirements for distinguishing the functional specificities of two
      homeodomain proteins, Antennapedia and Sex combs reduced, involved in the
      specification of segmental identities in Drosophila, have been determined. A
      series of deletions and hybrid proteins was generated and assayed for their
      function in vivo after heat shock-induced ectopic expression during development.
      A distinct portion of each protein, including the residues within and adjacent to
      both ends of the homeodomain, has been found to almost entirely determine its
      functional specificity as measured by diagnostic cuticular transformations of
      embryonic and adult head structures. The remaining sequences contribute to the
      potency with which the proteins act in different cells and are to a limited
      extent functionally transferable from one protein to the other.

PMID- 1976045
TI  - Loss of heterozygosity in mammalian cell mutagenesis: molecular analysis of
      spontaneous mutations at the aprt locus in CHO cells.
AB  - Loss of heterozygosity at previously heterozygous loci may occur by one of
      several possible mechanisms and account for a large fraction of all mutations
      occurring at such loci. In order to investigate loss of heterozygosity events, we
      have chosen the aprt locus of Chinese hamster ovary (CHO) cells as our model
      since it is readily available in either heterozygous or hemizygous form. Cloning
      and sequencing of the two heterozygous aprt alleles from the CHO derivative D423
      identified a single polymorphic site, which does not create a restriction
      fragment length polymorphism. In order to evaluate the loss of heterozygosity
      events at this locus, we devised a method that creates an artificial restriction
      fragment length polymorphism in one of these two alleles as a direct consequence
      of enzymatic amplification. Restriction enzyme digestion of the amplified
      sequences can then conveniently identify the genotype of the DNA sample. This
      same methodology also provides for the selective cloning of only one allele of a
      heterozygous pair into a plasmid vector for subsequent DNA sequence analysis, and
      can be easily adapted to other situations requiring the analysis of single base
      changes at a particular position within known sequences. Using this technique, we
      have determined that 16/37 (43%) spontaneous APRT- mutants had undergone a loss
      of heterozygosity event.

PMID- 1976046
TI  - Human debrisoquine hydroxylase gene polymorphisms in cancer patients and
      controls.
AB  - The extensive metabolizer phenotype of debrisoquine has been associated with
      increased risk of lung cancer, and it has been proposed that a molecular test for
      this phenotype is feasible. DNA restriction fragment length polymorphisms of the
      human debrisoquine 4-hydroxylase gene locus (CYP2D6), and the metabolic phenotype
      for debrisoquine have been studied in a group of healthy volunteers, a group of
      lung cancer patients and two control groups (chronic obstructive pulmonary
      disease patients and patients with cancers at sites other than the lung).
      Confirmation of four distinct XbaI allelic fragments (44, 29, 16/9 and 11.5 kb),
      previously identified among caucasians, was obtained. The 29 kb alleles were the
      most frequently observed in both poor and extensive metabolizers of debrisoquine.
      Alleles of 44 kb were found with approximately equal frequency among both poor
      and extensive metabolizers. The data are consistent with the hypothesis that the
      11.5 and 44 kb fragments are associated with mutant alleles of the CYP2D6 gene,
      but the power of phenotype prediction by these alleles was less than that
      previously reported for a European (Swiss-German) population. Similarly, the data
      also show that 8% of 29 kb homozygotes are poor metabolizers (indicating that at
      least 28% of 29 kb fragments are also associated with mutant alleles) and are not
      therefore informative for predicting the debrisoquine phenotype. The 16/9 allele
      may represent either wild-type or mutant alleles. Restriction fragments of 44 kb
      were found more frequently among cancer patients and chronic obstructive
      pulmonary disease patients (30%) than among the healthy volunteer group (7%).
      Genotypes observed were not related to lung tumor histology. Furthermore, at
      least three EcoRI alleles were found to be in linkage disequilibrium with the
      'mutant' 44 kb allele. These data suggest that the 44 kb allele can comprise
      three distinct haplotypes, in contrast to studies of a European population. These
      studies indicate that no single mutant CYP2D6 allele as determined by EcoRI
      appears to be associated with lung cancer, despite the findings that these
      patients are invariably of the extensive metabolizer phenotype.

PMID- 1976047
TI  - Ultrastructural changes in chemically induced preneoplastic focal lesions in the
      rat liver: a stereological study.
AB  - Ultrastructural changes were investigated and quantified, using a stereological
      approach, in early gamma-glutamyltranspeptidase (GGT)-positive focal lesions,
      induced in the rat liver by treatment with a single initiating dose of
      diethylnitrosamine (DENA) followed by promotion with phenobarbitone (PB) for 30
      weeks. Within the extra-hepatocyte environment of focal tissue, the mean volume
      occupied by Ito cells was markedly decreased, whilst that occupied by endothelial
      and Kupffer cells was increased, when compared to uninvolved tissue from the same
      rat livers. The bile canaliculi were dilated, but no significant differences in
      the mean volume occupied by the sinusoidal and Disse spaces were noted. In focal
      hepatocytes there was a striking overproduction of lipid droplets and
      proliferation of smooth endoplasmic reticulum (sER). Whorls of concentrically
      arranged, parallel ER membranes were found only in the hepatocytes of
      preneoplastic foci, in association with the proliferated sER, and never in the
      surrounding, uninvolved tissue. The increase in mean volume of the sER, lipid
      droplet and cytoplasmic matrix compartments, together with the appearance of
      whorls, were the major contributing factors to the marked hypertrophy seen in
      focal hepatocytes. The mean volume of the rough endoplasmic reticulum,
      mitochondrial, lysosomal, peroxisomal and nuclear compartments per hepatocyte
      also increased, but contributed to a lesser extent to the cellular hypertrophy.
      It is speculated that whorls may be structural adaptations, resulting from a
      possible alteration in the normal feedback control of cholesterol synthesis, for
      the production of sterols and the biogenesis of sER in eosinophilic-type focal
      cells. The significance of changes observed in focal tissue, and the high
      biological variation noted between foci, is discussed in relation to the
      hepatocarcinogenic process.

PMID- 1976048
TI  - Minimum left ventricular pressure during beta-adrenergic stimulation in human
      subjects. Evidence for elastic recoil and diastolic "suction" in the normal
      heart.
AB  - The influence of elastic recoil and restoring forces on diastolic left
      ventricular pressure decay and minimum left ventricular pressures has been
      demonstrated in animal models but has not been studied in the human heart. To
      investigate this issue in the normal human left ventricle, we studied eight
      patients with chest pain and normal coronary arteries with simultaneous
      measurement of left ventricular volume (by radionuclide angiography) and pressure
      (by micromanometer catheter) and coronary sinus blood flow. Electrocardiographic
      gated data were obtained in the basal state, during rapid atrial pacing, and
      during isoproterenol infusion to a similar heart rate. Compared with pacing,
      isoproterenol increased ejection fraction and reduced end-systolic volume (p less
      than 0.005), end-systolic pressure (p less than 0.005), and the half-time of
      pressure decline after peak negative dP/dt (T1/2) (p less than 0.001). Negative
      diastolic pressure developed in seven of eight patients during isoproterenol
      (range, -0.5 to -2.4 mm Hg) but in only one of eight during pacing (-0.2 mm Hg).
      These reduced diastolic pressures during isoproterenol were accompanied by
      increased stroke volume (reflecting increased transmitral flow) and diminished
      pulmonary wedge pressure (reflecting left atrial pressure). The magnitude of
      reduction in minimum diastolic pressure during pacing and isoproterenol was
      related to the change in end-systolic volume (r = 0.79, p less than 0.001),
      ejection fraction (r = -0.74, p less than 0.001), T1/2 (r = -0.57, p less than
      0.02), and coronary sinus flow (r = 0.73, p less than 0.005). Stronger
      correlations were observed in analyzing changes during isoproterenol
      alone.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1976049
TI  - Pathophysiology of silent myocardial ischemia during daily life. Hemodynamic
      evaluation by simultaneous electrocardiographic and blood pressure monitoring.
AB  - The role of myocardial oxygen demand in the genesis of silent myocardial ischemia
      was evaluated by measuring the heart rate and blood pressure changes preceding
      the silent ischemic events during daily life in 25 men with proven coronary
      artery disease. Simultaneous 24-48-hour ambulatory electrocardiographic and blood
      pressure monitoring were performed during unrestricted daily activities. Of the
      92 transient ischemic events recorded during monitoring, 85 (92%) were silent.
      Sixty-one percent of the silent events were preceded by an increase in the heart
      rate of 5 beats/min or more. Seventy-three percent of the silent ischemic events
      showed an average increase of 10 mm Hg in systolic blood pressure within 6
      minutes preceding the onset of ST segment depression. The silent ischemic events
      showed a circadian pattern with a high density (34% of total events) between 6:00
      AM and noon. The increase in heart rate and blood pressure paralleled the
      increase in silent ischemic events during these hours. These results showing
      significant (p less than 0.001 for both) increases in heart rate and blood
      pressure preceding a majority of silent ischemic events suggest that increase in
      myocardial oxygen demand plays a significant role in the genesis of silent
      ischemia. This pathophysiological mechanism has important therapeutic
      implications.

PMID- 1976050
TI  - Unraveling the mechanisms of ambulatory ischemia. How and why.

PMID- 1976053
TI  - Dyspnea in the patient with chronic obstructive pulmonary disease. Etiology and
      management.
AB  - We have summarized much of the known information regarding the pathogenesis of
      dyspnea in the COPD patient and have reviewed a great many of the therapeutic
      options that have been investigated. It should be obvious that we are really in
      the early stages of our understanding about this symptom, and that we know very
      little about how to decide which treatment options are likely to succeed in any
      individual. At this time, there is no substitute for a careful assessment of each
      treatment modality that is instituted using a measurement tool, and the value of
      a comprehensive assessment as outlined cannot be overemphasized.

PMID- 1976052
TI  - Hemodynamic effects of different H2-receptor antagonists.
AB  - In a randomized, placebo-controlled, double-blind study, 10 healthy volunteers
      were treated orally once a day for 1 week each with placebo, 800 mg cimetidine,
      300 mg ranitidine, and 40 mg famotidine. On the seventh treatment day, heart
      rate, blood pressure, systolic time intervals, and impedance cardiography were
      measured before the morning dose and at 2, 6, 12, and 24 hours after the morning
      dose. Heart rate and blood pressure were not markedly altered by any of the H2
      receptor antagonists compared with the findings for placebo. Cimetidine and
      ranitidine did not markedly alter parameters of systolic time interval and
      impedance cardiography compared with placebo in contrast to famotidine, which
      significantly decreased stroke volume, cardiac output, and the Heather Index in
      impedance cardiography (p less than 0.05) and also significantly increased the
      ratio of the preejection period to the left ventricular ejection time in systolic
      time interval (p less than 0.05) 2 hours after the morning dose. Six hours after
      administration, most of these alterations could no longer be detected. The
      observed changes in hemodynamic parameters confirm that famotidine exerts
      negative effects on cardiac performance, whereas such influences could not be
      shown for cimetidine and ranitidine.

PMID- 1976051
TI  - The pulmonary and extrapulmonary effects of inhaled beta-agonists in patients
      with asthma.
AB  - The cardiovascular, respiratory, and hypokalemic effects of repeated inhalation
      of fenoterol, albuterol, and isoproterenol were compared in 12 subjects with
      stable asthma according to a double-blind, crossover design. Ipratropium bromide
      served as a control providing bronchodilatation without extrapulmonary effects.
      Subjects inhaled the beta-agonists on an equal-weight basis (400 micrograms) at
      0, 30, 40, and 45 minutes. Measurements of heart rate, blood pressure, total
      electromechanical systole (measure of inotropic activity), preejection period,
      QTc interval, plasma potassium levels, and forced expiratory volume in 1 second
      were made 5 minutes after each dose and again at 60 and 75 minutes. There were no
      differences in the bronchodilating effect between the beta-agonists. However,
      both fenoterol and isoproterenol resulted in greater positive inotropic
      stimulation than did albuterol, and fenoterol caused a greater fall in plasma
      potassium levels than did the other beta-agonists.

PMID- 1976054
TI  - Cor pulmonale in chronic obstructive pulmonary disease. Circulatory
      pathophysiology and management.
AB  - The development of pulmonary hypertension and right ventricular failure in COPD
      patients signals a poor prognosis. In hypoxic patients, long-term oxygen therapy
      prolongs life and appears to prevent or lessen the progression of pulmonary
      hypertension. However, oxygen therapy does not benefit and is not indicated for
      all COPD patients, and even in those patients who improve with oxygen, there
      remains a need to further improve survival. Therefore, there continues to be
      active investigations into pharmacologic agents that might reduce pulmonary
      hypertension or improve right ventricular function. Although many agents appear
      to have salutary acute effects, it has been more difficult to establish evidence
      for sustained hemodynamic benefits from chronic drug therapy. Furthermore, some
      effective agents may not provide additive benefit when combined with standard
      supplemental oxygen use, although the available data are limited. Clearly,
      further research is necessary to identify which COPD patients, if any, may
      benefit from either beta-agonists or vasodilators for the treatment or prevention
      of cor pulmonale at some time during the natural history of their disease.

PMID- 1976056
TI  - Comment: Pharmaceutics of acetaminophen, vancomycin, and antipyrine on the
      Hanford miniature swine.

PMID- 1976057
TI  - Interspecies differences in stereoselective protein binding and clearance of MK
      571.
AB  - (+)-3-(((3-(2-(7-chloro-2-quinolinyl)ethenyl)phenyl)((3-(dimethylamino)- 3
      oxopropyl)thio)methyl)thio)propanoic acid (MK-571), is a potent and specific
      antagonist of leukotriene D4 action in vitro and in vivo. The compound, which is
      being developed for the treatment of asthma, contains a chiral center at the
      methine carbon of the dithio side chain and exists in two forms. The binding of
      MK-571 enantiomers to plasma protein was extensive (greater than 99.5%),
      stereoselective, and species dependent. The R-(-)-enantiomer was bound to rat
      plasma to a greater extent than the S-(+)-enantiomer, while in dog and monkey
      plasma the reverse was the case. The elimination clearance of the enantiomers was
      inversely related to the stereoselective plasma protein binding, that with the
      greater unbound fraction being cleared more rapidly. Thus, the pharmacologically
      more active S-(+)-enantiomer was cleared 3.7 times more rapidly than its antipode
      in rats following iv administration of the racemate (10 mg/kg), whereas in dogs
      and monkeys the R-(-)-enantiomer was cleared more rapidly. Kinetic analysis of
      the data revealed that the intrinsic clearances of the unbound enantiomers were
      similar within species, suggesting that stereoselectivity in elimination is not
      attributable to differences in metabolism and biliary excretion.
      Bioavailabilities of the S-(+)- and R-(-)-enantiomers in the rat were similar
      (75% and 71%, respectively) suggesting that MK-571 was not stereoselectively
      absorbed in that species.

PMID- 1976055
TI  - Investigations on the binding properties of the nootropic agent pyroglutamic
      acid.
AB  - The two stereoisomers of pyroglutamic acid (PCA), a nootropic or cognition
      enhancing agent, and classic reference compounds were investigated for their
      ability to interact with 27 neurotransmitter receptors and drug binding sites
      prepared from selected areas of the central nervous system and labelled with high
      affinity and selectivity with specific radioligands. L-PCA significantly
      interacted with the rat forebrain excitatory amino acid receptors labelled with
      3H-L-glutamic acid. The IC50 of L-PCA was 28.11 microM, that of cold L-glutamic
      acid was 1.68 microM. The corresponding figure for L-aspartic acid was 16.95
      microM. The indirect Hill plot gave coefficients of 0.48, 1.08 and 0.75 for L
      PCA, L-glutamic and L-aspartic acids, respectively. Only very high concentrations
      (10(-4) M) of L-PCA were able to slightly antagonize the specific binding of 3H
      clonidine to alpha 2-adrenergic receptors, of 3H-dihydroalprenolol to beta 1- and
      beta 2-adrenergic receptors of the heart and of the lung and of 3H-diazepam to
      benzodiazepine receptors. The D-isomer of PCA was practically as active as the L
      isomer on these receptors. Finally, L-PCA (10(-5) to 10(-4) M) was unable to
      antagonize the specific binding of all the other radioligands to their respective
      receptors and binding sites. D-PCA did not significantly interact with excitatory
      amino acid receptors or with any of the other sites studied here.

PMID- 1976058
TI  - Comparison of the interaction of pyrazole and its metabolite 4-hydroxypyrazole
      with rat liver microsomes.
AB  - Pyrazole is known to interact with and to induce cytochrome P-450 IIE1. Since
      pyrazole is oxidized by rat liver microsomes to 4-hydroxypyrazole, and several of
      the actions of pyrazole have been ascribed to its metabolite, experiments were
      conducted to evaluate the interactions of 4-hydroxypyrazole with microsomes, and
      to compare these to pyrazole itself. Rats were injected with doses of 4
      hydroxypyrazole ranging from 2 to 100 mg/kg body weight/day for 2 days. A slight
      increase of total cytochrome P-450 was observed at low doses, followed by a
      decrease at higher concentrations. NADPH-cytochrome P-450 reductase activity was
      not affected. The oxidation of aniline or dimethylnitrosamine was increased about
      50% by the 4-hydroxypyrazole treatment; however, this extent of increase was much
      less than that produced by pyrazole treatment. In vitro, 4-hydroxypyrazole
      produced a type II binding spectrum with microsomes, with a peak at about 425 nm
      and a trough at about 395 nm. The affinity for 4-hydroxypyrazole was increased
      from a value of about 0.60 mM in control microsomes to a value of about 0.40 mM
      in microsomes from pyrazole-treated rats. These values are 2-fold greater than
      those observed with pyrazole as the ligand. 4-Hydroxypyrazole inhibited the
      microsomal oxidation of ethanol; kinetics of inhibition were mixed. The apparent
      KI for 4-hydroxypyrazole inhibition of ethanol oxidation by microsomes was about
      4 mM, which is about an order of magnitude greater than that for pyrazole. The in
      vivo and in vitro interactions of 4-hydroxypyrazole with microsomes appear to be
      similar to those described for pyrazole; however, these interactions are
      considerably less effective than those of the parent drug, pyrazole. Thus,
      although some actions of pyrazole may be due to the metabolite 4-hydroxypyrazole,
      it appears that the induction of P-450 IIE1 and the in vitro interactions of
      pyrazole with microsomes is not likely to be mediated by prior metabolism of
      pyrazole to 4-hydroxypyrazole.

PMID- 1976060
TI  - Effects of thyroid dysfunction on prednisolone and prednisone interconversion and
      disposition in the rat.
AB  - The effects of thyroid dysfunction on the reversible metabolism and disposition
      of prednisolone and prednisone were examined in male Wistar rats. Hyperthyroid
      rats were produced by daily ip injections of 20 micrograms of I
      triiodothyronine/100 g body weight for 6 days. Hypothyroid rats were obtained by
      providing 0.05% 6-propyl-2-thiouracil in drinking water ad libitum for 21 days.
      Rats were given 10 mg/kg of prednisolone or prednisone iv, blood samples were
      collected, and the steroids in plasma were assayed by HPLC. A recently developed
      pharmacokinetic model encompassing interconversion kinetics was applied.
      Unexpectedly, the hyperthyroid state increased the AUC (by 163%) of prednisolone
      (unlike in man) via reduced (66%) prednisolone elimination clearance (CL10), but
      also caused enhanced (101%) prednisone elimination clearance (CL20). The
      hypothyroid state increased the AUC (by 117%) of prednisolone via a 56% reduction
      in CL10 and a reduction in CL20. Prednisone formation of prednisolone (CL21) was
      about 13-fold greater than the reverse process (CL12), and both interconversion
      clearances were increased 20-40% by thyroid dysfunction. Experimental thyroid
      disorders thus alter prednisolone/prednisone pharmacokinetics in rats primarily
      by selective and sometimes unusual changes in elimination clearance rather than
      affecting the relative rates of steroid interconversion. Reversible metabolism is
      much less important in rats compared to man.

PMID- 1976059
TI  - Tissue, species, and substrate concentration differences in the position
      selective hydroxylation of N-nitrosodibutylamine. Relationship to the
      distribution of cytochrome P-450 isozymes 2 (IIB) and 5 (IVB).
AB  - The relative rates of 3- and 4-hydroxylation of N-nitrosodibutylamine in
      microsomal preparations depend upon species, tissue, and substrate concentration.
      With rabbits, at a substrate concentration of 200 microM, the two reactions
      differ by less than 30% in preparations from liver, lung, or intestine, whereas
      the ratio of 4- to 3-hydroxylation is 2.0 with bladder and only 0.4 with kidney.
      As the substrate concentration is lowered, this ratio increases to a maximum of
      about 2.0 in hepatic and pulmonary preparations. The sum of the rates of 3- and 4
      hydroxylation of N-nitrosodibutylamine in microsomal preparations from untreated
      rabbits is highest in those from lung (about 2-fold greater than liver).
      Following treatment of rabbits with phenobarbital, however, the highest rate is
      with hepatic microsomes (about 2-fold greater than pulmonary microsomes).
      Antibodies to cytochrome P-450 isozymes 2 (IIB) and 5 (IVB) together inhibit
      greater than 90% of the microsomal 3- and 4-hydroxylation of N
      nitrosodibutylamine. The ratio of 4- to 3-hydroxylation with antibodies to
      isozyme 2 present is the same (2.0) as that obtained with purified isozyme 5, and
      the ratio with antibodies to isozyme 5 present is the same (0.2) as that with
      purified isozyme 2. The Km with isozyme 5 is less than 10 microM, whereas the Km
      with isozyme 2 is 55 microM, a difference that explains why position selectivity
      in microsomal incubations is dependent upon substrate concentration. Also,
      differences in the relative and absolute rates of hydroxylation among various
      tissues reflect differences in the contents of isozymes 2 and 5.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1976061
TI  - Metabolic fate of alclometasone dipropionate in rats, rabbits, and mice.
      Metabolic products and pathway following subcutaneous administration.
AB  - The metabolic fate of alclometasone dipropionate (ADP or S-3460) has been studied
      in rats, rabbits, and mice, with consideration of their interspecies differences.
      Several reference compounds related to ADP were synthesized for the determination
      and identification of the metabolites. After sc administration of 14C-labeled
      ADP, the metabolites in plasma, bile, and urine were separated and analyzed using
      TLC-ARG (autoradiography) and HPLC in comparison with the reference compounds.
      The metabolites identified, fully or tentatively, by MS and 1H-NMR totaled 11.
      The metabolic transformations were: hydrolysis of the side chain esters,
      dehydrochlorination leading to the formation of delta 6-double bond, 6 beta
      hydroxylation, 6 beta, 7 beta-epoxides from 6 beta-hydroxylated metabolites, side
      chain oxidation to 21-oic and 20-oic acids in the 6 beta-hydroxylated
      metabolites, and conjugation to glucuronides and sulfates. The metabolic pathway,
      postulated on the basis of the identified and quantitated metabolites, was a
      rapid hydrolysis of 21-ester of ADP to the corresponding alcohol, M-1, after
      systemic uptake. This M-1 was a main metabolite in plasma of animals studied, and
      due to its relatively longer life time in the media, it seemed to allow a variety
      of metabolism to occur, giving the oxidative and conjugative metabolites
      mentioned above.

PMID- 1976062
TI  - The role of cytochromes P-450 and flavin-containing monooxygenase in the
      metabolism of (S)-nicotine by rabbit lung.
AB  - Rabbit lung microsomes metabolize (S)-nicotine primarily to (S)-nicotine delta
      1',5'-iminium ion, which is the precursor of (S)-cotinine, the major urinary
      metabolite of (S)-nicotine in mammals. (S)-Nicotine-N'-oxide and normicotine are
      also produced as minor metabolites. alpha-Methylbenzylaminobenzotriazole, a
      mechanism-based suicide inhibitor of rabbit lung cytochromes P-450 2 and 6,
      inhibited (S)-nicotine oxidation in parallel with inhibition of benzphetamine N
      demethylation and ethoxyresorufin O-deethylation. Pretreatment of rabbits with
      TCDD or Aroclor 1260 had no effect and markedly inhibited (S)-nicotine oxidation,
      respectively, strongly suggesting that alpha-methylbenzylaminobenzotriazole
      inhibition was due to inactivation of rabbit lung P-450 2. Reconstitution with
      cytochromes P-450 2 and 5 demonstrated that only P-450 2 was active toward (S)
      nicotine, yielding predominantly the iminium ion, with smaller amounts of
      nornicotine, (S)-nicotine N'-oxide, and an unknown metabolite also detected. The
      purified rabbit lung P-450 2-catalyzed oxidation of (S)-nicotine to (S)-nicotine
      delta 1',5'-iminium ion exhibited a Km of 70 microM and a Vmax of 1.5 min.
      Covalent binding of (S)-5-3H-nicotine to rabbit lung macromolecules was dependent
      upon rabbit lung P-450 2-catalyzed formation of the iminium ion. Antibodies
      raised against P-450 2 inhibited the rabbit lung microsomal metabolism of (S)
      nicotine to (S)-nicotine delta 1',5'-iminium ion by almost 95%. Titration of
      reconstituted P-450 2 with cytochrome b5 produced a concentration-dependent
      inhibition of nicotine oxidase activity. Increasing the ratio of NADH to NADPH in
      incubations containing lung microsomes and (S)-nicotine decreased the yield of
      the iminium ion, confirming the inhibitory effect of cytochrome b5 on the P-450 2
      catalyzed alpha-carbon oxidation reaction. NADH alone did not support the lung
      microsomal metabolism of (S)-nicotine. N'-oxidation of (S]-nicotine is catalyzed
      by purified pig liver flavin-containing monooxygenase. A number of experiments
      involving the use of P-450 inhibitors, titration with NADPH-cytochrome P-450
      reductase antibodies, and determination of the pH-enzyme activity profile
      suggested that rabbit lung flavin-containing monooxygenase contributes to a small
      amount of the N'-oxide produced by rabbit lung microsomes. Further examination
      with purified flavin-containing monooxygenase isolated from rabbit lung
      microsomes demonstrated that (S)-nicotine is a poor substrate for this enzyme.
      The low yield of N'-oxide, relative to other metabolites, in rabbit lung is
      uncharacteristic for most mammalian tissues and presumably reflects the unusual
      substrate specificity of rabbit lung flavin-containing monooxygenase.

PMID- 1976063
TI  - A pharmacokinetic model for isosorbidedinitrate, isosorbide-2-mononitrate, and
      isosorbide-5-mononitrate.
AB  - A pharmacokinetic model is proposed to describe the plasma levels of
      isosorbidedinitrate (ISDN) and its two pharmacologically active metabolites,
      isosorbide-2-mononitrate (IS-2MN) and isosorbide-5-mononitrate (IS-5MN),
      following the oral administration of several 20-mg sustained release formulations
      of ISDN. Absorption of ISDN from the gastrointestinal tract appears first-order.
      A three compartment model is used to describe ISDN systemic plasma levels with
      t1/2 alpha = 7 min, t1/2 beta = 48 min and t1/2 gamma = 7.5 hr. The long t1/2
      gamma is due to the slow release of ISDN from a peripheral compartment. ISDN
      undergoes extensive first-pass hepatic metabolism to IS-2MN and IS-5MN. The
      metabolic pathways appear to be close to saturation at an ISDN dose of 20 mg.
      Both IS-2MN and IS-5MN systemic plasma levels can be described by one compartment
      models with first-order elimination (respective elimination half-lives are 1.9
      and 5.1 hr). The central compartment volumes of distribution for ISDN, IS-2MN and
      IS-5MN (116, 57, and 38 liters, respectively) are in agreement with reported
      literature values. This model is of particular usefulness as a formulation tool
      in designing sustained release ISDN formulations of the type investigated here
      since the observed first-order absorption rate constant correlates well with the
      in vitro first-order dissolution rate constant. Therefore, for these
      formulations, plasma levels can be simulated using data generated from in vitro
      dissolution studies, thus obviating the need for multiple human bioavailability
      studies.

PMID- 1976064
TI  - Interspecies comparison of the pharmacokinetics of aldose reductase inhibitors.
AB  - The pharmacokinetics of three aldose reductase inhibitors (ARIs) were evaluated
      in various species, including rat, dog, cynomolgus monkey, rhesus monkey,
      chimpanzee, and man. The three ARIs (AL01567, AL01576, and AL01750) were
      administered intravenously as a single dose to all species except rat, which was
      dosed orally with AL01750, and man, who was dosed orally with AL01567 and
      AL01576. Plasma drug concentrations were measured by HPLC or liquid scintillation
      spectrometry and various pharmacokinetic parameters (clearance, CL; Vd, volume of
      distribution; and t1/2) were calculated from the data. Overall the
      pharmacokinetics of the three compounds were quite similar, each being
      characterized by low CL, intermediate Vd, and long t1/2. For AL01576, mean CL
      ranged from 0.21 ml/min/kg in cynomolgus monkey to 0.91 ml/min/kg in dog, mean Vd
      from 0.66 liter/kg in cynomolgus monkey to 2.4 liters/kg in dog and man and mean
      t1/2 from 29 hr in dog to 72 hr in man. Mean CL of AL01567 ranged from 0.14
      ml/min/kg in man to 1.4 ml/min/kg in dog, mean Vd from 0.45 liter/kg in rat to
      3.5 liters/kg in dog and mean t1/2 from 22 hr in rhesus monkey to 63 hr in man.
      Mean CL of AL01750 ranged from 0.13 ml/min/kg in chimpanzee to 1.3 ml/min/kg in
      dog, mean Vd from 0.40 liter/kg in rat to 1.8 liters/kg in dog and mean t1/2 from
      12 hr in rhesus monkey to 62 hr in chimpanzee. For all three drugs, CL and Vd
      corrected for body weight were quite similar in all species except dog, whose CL
      and Vd were two- to fourfold greater than the other animals.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1976065
TI  - Metabolism and disposition of clarithromycin in man.
AB  - The metabolic fate and pharmacokinetics of clarithromycin following a single 250-
      or 1200-mg oral dose of 14C-clarithromycin were studied in six healthy adult
      males. Peak plasma levels of clarithromycin averaged 0.6 microgram/ml after the
      low dose and 2.7 micrograms/ml after the high dose. The AUC of clarithromycin
      increased 13-fold, with the 4.8-fold increase in dose, while the plasma half-life
      increased from 4.4 hr to 11.3 hr. The major metabolite in plasma and urine was
      the microbiologically active 14-hydroxylated-R epimer of clarithromycin. After 5
      days, a mean of 38% of the low dose (18% as clarithromycin) and 46% of the high
      dose (29% as clarithromycin) was recovered in the urine, with approximately one
      third eliminated during the first 24 hr. The nature of the urinary and fecal
      metabolites revealed the involvement of three metabolic pathways, viz. 1)
      hydroxylation at the 14-position to form the R and S epimers, 2) N-demethylation,
      and 3) hydrolysis of the cladinose sugar. Secondary metabolism via these pathways
      was also evident. The overall recovery of metabolites, but not total
      radioactivity, decreased 42% after the high dose. The nonlinear pharmacokinetic
      behavior of clarithromycin and the decrease in metabolite production suggest that
      clarithromycin metabolism can be saturated at high doses.

PMID- 1976066
TI  - Deuterium isotope effect on the toxicokinetics of monomethylamine in the rat.
AB  - The single-dose toxicokinetics of monomethylamine has been characterized in the
      rat by HPLC assay of serial blood samples. Biphasic first-order elimination was
      observed following an iv bolus dose of 19 mumol/kg with a terminal half-life of
      19.1 +/- 1.3 min (mean +/- SE, N = 4). The apparent steady state volume of
      distribution, systemic blood clearance, and renal blood clearance were 1.21 +/-
      0.09 liter/kg, 53.4 +/- 3.5 ml/min/kg, and 5.72 +/- 0.53 ml/min/kg, respectively.
      The administration of an intragastric dose permitted the calculation of the
      systemic bioavailability of monomethylamine as 69 +/- 3%. Duplicate experiments
      using the structural analogue with deuterium atoms substituted for hydrogens on
      the methyl group revealed a much slower elimination of the compound, although
      ultimately, 5 times as much was excreted unchanged in the urine. Isotope effects
      calculated as the ratios of terminal half-life, systemic blood clearance, and
      systemic bioavailability were 1.9, 2.2, and 1.8, respectively.

PMID- 1976067
TI  - N-depyridination and N-dedimethylaminoethylation of tripelennamine and pyrilamine
      in the rat. New metabolic pathways.
AB  - N-(2-Dimethylaminoethyl)benzylamine and 2-benzylaminopyridine were identified as
      two new urinary metabolites of tripelennamine in the rat by GC/MS. 2-(4
      Methoxybenzylamino)-pyridine and N-(dimethylaminoethyl)-4-hydroxybenzylamine were
      identified as new urinary metabolites of pyrilamine by GC/MS. Thus, in addition
      to N- and O-demethylation, hydroxylation, and glucuronidation, N-debenzylation, N
      depyridination and N-dedimethylaminoethylation were shown to be novel pathways
      for metabolism of tripelennamine and pyrilamine. The mechanism for N
      depyridination and N-dealkylation is discussed.

PMID- 1976068
TI  - Stimulation mechanism of guinea pig liver-mediated reduction of naloxone by
      morphine.
AB  - The mechanism of the stimulatory effect of morphine on the reduction of naloxone
      has been elucidated using guinea pig liver naloxone reductase that is identical
      with morphine 6-dehydrogenase. The reaction products were quantitated by means of
      HPLC. When naloxone was incubated with the enzyme in the presence of NAD(P)H at
      pH 7.4 or pH optima, the production of 6 alpha-naloxol increased according to the
      added amount of morphine. The stimulation was predominant with NADH at pH 7.4.
      Under these conditions, the production of morphinone also increased in proportion
      to the amount of morphine. The enzymatic reduction of naloxone proceeded even if
      NAD(P)H was replaced by NAD(P)+ and morphine. At a fairly low concentration of
      NADH (0.01 mM), the enzyme produced 6 alpha-naloxol (0.3 mM), exceeding the
      stoichiometric amount in the presence of 16 mM morphine. Although the Vmax values
      for naloxone was increased by the addition of morphine, the Km values for
      naloxone remained unaltered. Besides other substrates for guinea pig liver
      morphine 6-dehydrogenase such as codeine, normorphine and ethylmorphine also
      enhanced the reduction of naloxone. From these results we concluded that the
      stimulation of guinea pig liver-mediated reduction of naloxone by morphine is
      caused by the acceleration of the redox of pyridine nucleotides conducted by the
      enzyme. These phenomena were further supported by the experiments with the liver
      cytosol. In addition, we confirmed that, in the guinea pig, the biliary excretion
      of the metabolites, naloxol and naloxol-3-glucuronide, increased after sc
      injection of naloxone with morphine.

PMID- 1976069
TI  - Effect of recombinant human interleukin-1 beta and tumor necrosis factor alpha on
      liver cytochrome P-450 and serum alpha-1-acid glycoprotein concentrations in the
      rat.
AB  - Two hepatocyte-related effects of recombinant human interleukin-1 beta and tumor
      necrosis factor alpha alone or in association were tested following iv
      administration to Fischer 344 rats. Within 24 hr, both monokines induced a dose
      dependent decrease in cytochrome P-450 levels, whereas serum alpha-1-acid
      glycoprotein concentrations were strongly increased. The largest variation of
      both parameters was observed using a combination of the two monokines.
      Dexamethasone, which possesses anti-interleukin-1 properties and is known to
      stimulate alpha-1-acid glycoprotein synthesis in rats, also depressed cytochrome
      P-450 levels, suggesting that alpha-1-acid glycoprotein might mediate the
      monokine-related inhibition of drug metabolism. Nevertheless, at the lowest doses
      of monokines tested, only cytochrome P-450 levels were modified. The transfer of
      a post-dexamethasone serum to normal rats did not change cytochrome P-450 levels.

PMID- 1976070
TI  - The pharmacokinetics of etodolac enantiomers in the rat. Lack of pharmacokinetic
      interaction between enantiomers.
AB  - Pharmacokinetics of the enantiomers of the nonsteroidal anti-inflammatory drug
      etodolac (ET, (+/- )-1,8-diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indole-1-acetic
      acid), which is marketed as a racemate, were studied in male Sprague-Dawley rats.
      Following administration of iv racemate, plasma concentrations of inactive R-ET
      were much greater than those of active S-ET. After iv doses of individual
      enantiomers, similar results were found, with significantly greater t1/2, CL, and
      Vdss, and lower AUC, for S- than for R-ET. No evidence of a pharmacokinetic
      interaction between the enantiomers was observed. Secondary peaks indicative of
      extensive enterohepatic recirculation were seen in plasma time courses of S-ET.
      In bile duct-cannulated rats, the AUC of S- but not R-ET, was significantly
      reduced, and secondary peaks were absent in plasma profiles. The differences
      between enantiomers were attributed to a greater extent of plasma protein binding
      of R-ET, and to preferential conjugation and biliary excretion of S-ET. Complete
      recovery of S-ET was achieved in bile, whereas only 30% of the R-enantiomer was
      recovered via this route of elimination. Urine was a minor route of elimination
      of ET. It was concluded that the rat may be a suitable pharmacokinetic model for
      the study of stereoselective pharmacokinetics of ET because, in some aspects, the
      results closely paralleled those of ET in man.

PMID- 1976071
TI  - In vitro and in vivo biotransformation of simvastatin, an inhibitor of HMG CoA
      reductase.
AB  - Simvastatin (SV), an analog of lovastatin, is the lactone form of 1', 2', 6', 7',
      8', 8a'-hexahydro-3,5-dihydroxy-2', 6'-dimethyl-8' (2", 2"-dimethyl-1"-oxobutoxy)
      1'-naphthalene-heptanoic acid (SVA) which lowers plasma cholesterol by inhibiting
      3-hydroxy-3-methylglutaryl-CoA reductase. SV but not its corresponding hydroxy
      acid form SVA underwent microsomal metabolism. Major in vitro metabolites were 6'
      OH-SV (I) and 3"-OH-SV (III) formed by allylic and aliphatic hydroxylation,
      respectively, and 6'-exomethylene-SV (IV) formed by dehydrogenation. In rats,
      dogs, and humans, biliary excretion is the major route of elimination. Biliary
      metabolites (as both hydroxy acids and lactones) also included 6'-CH2OH-SV (V)
      and 6'-COOH-SV (VI) in both of which the 6'-chiral center had been inverted. High
      levels of esterase in rodent plasma favored the formation of SVA from SV. The
      formation of 1', 2', 6', 7', 8', 8a'-hexahydro-2', 6'-dimethyl-8'-(2",2"-dimethyl
      1-oxobutoxy)-1'-naphthalene-pentano ic acid (VII) only in rodents represented a
      species difference in the metabolism of SV. It is proposed that VII is formed by
      beta-oxidation pathways of fatty acid intermediary metabolism. Several
      metabolites resulting from microsomal oxidation (after subsequent conversion from
      lactones to hydroxy acids) are effective inhibitors of 3-hydroxy-3-methylglutaryl
      CoA reductase and may contribute to the cholesterol lowering effect of SV.
      Qualitatively, the metabolism of SV closely resembles that of lovastatin.

PMID- 1976072
TI  - Species-dependent enantioselective plasma protein binding of MK-571, a potent
      leukotriene D4 antagonist.
AB  - The plasma protein binding of the enantiomers of MK-571 was stereoselective and
      the stereoselectivity was species dependent. The 12 mammalian species studied
      could be classified into three groups: those that bind the S-(+)-enantiomer to a
      greater extent than the R-(-)-enantiomer (human, baboon, monkey, cow, dog, and
      cat); those that bind the R-(-)-enantiomer more extensively (rat, guinea pig, and
      sheep); and those that show no stereoselectivity (rabbit, hamster, and mouse).
      The stereoselective binding appears to have no phylogenetic relationship. Using
      serum albumin instead of plasma, a similar degree of stereoselective binding was
      observed for human, dog, sheep, and rat, suggesting that albumin is the major
      binding component for MK-571 enantiomers, and that species differences in
      stereoselective binding are likely due to structural differences in the albumin
      molecule. Displacement studies with [14C] diazepam, [14C]warfarin, and
      [3H]digitoxin indicated that the enantioselective differences in protein binding
      are most likely due to the differences in binding affinity rather than to
      different binding sites.

PMID- 1976074
TI  - Effects of age and dose on disposition and metabolism of salicylic acid in male
      Fischer 344 rats.
AB  - Salicylic acid (SAL)-induced nephrotoxicity has been reported to be greater in
      older rats. To examine age- and dose-related changes in disposition and
      metabolism, male Fischer 344 rats aged 3, 12, and 25 months were administered
      single doses of 14C-SAL at 5,50, and 500 mg/kg po. At 5 mg 14C-SAL/kg, urinary
      excretion of 14C-SAL derived radioactivity (RA) followed first-order kinetics and
      was complete by 24 hr in 3- and 25-month-old rats, but not until 48 hr in 12
      month-old rats. The percentage of administered 14C-SAL excreted as the oxidative
      metabolites 2,3- and 2,5-dihydroxybenzoic acid (2,3- and 2,5-diOH), unmetabolized
      SAL, or salicyl ester glucuronide (SA-AG) was unchanged with age. The percentage
      excreted as the ether glucuronide (SA-PC) was significantly decreased in 25-month
      old rats, while the percentage excreted as the glycine conjugate, salicyluric
      acid (SUA) was significantly increased in 12- and 25-month-old rats. At 50 mg
      SAL/kg, urinary elimination shifted toward zero-order kinetics and was not
      complete until 48 hr in all age groups. The percentage of an administered dose of
      14C-SAL found in urine as 2,3- and 2,5-diOH and SA-AG increased significantly in
      all age groups, while the percentage excreted as SUA decreased significantly.
      Twelve- and 25-month-old rats excreted a significantly greater percentage of the
      total dose as 2,3- and 2,5-diOH than 3-month-old rats at this dose. No SA-PG was
      detected at this dose in any age group. At 500 mg SAL/kg, mortality was observed
      in both 3- and 25-month-old rats and excretion of SAL-derived RA in urine was
      incomplete at 48 hr. However, data indicated a further shift in biotransformation
      toward increased production of oxidative metabolites and a decrease in SUA
      production. No significant overall differences were observed between 3- and 25
      month-old rats in plasma levels of 14C-SAL following iv administration of 5 and
      50 mg SAL/kg. However, elimination half-life (t1/2) was significantly increased
      in 25-month-old rats at 5 mg SAL/kg vs. 3-month-old rats. These results indicate
      that the age-related increase in acute nephrotoxicity of SAL may result from
      increased production of oxidative metabolites in older rats at higher doses of
      SAL.

PMID- 1976073
TI  - Structural determination of the conjugated metabolites of ritodrine.
AB  - Ritodrine is a beta-2 adrenergic agonist which is used clinically for the
      management of preterm labor. Since ritodrine is resistant to the action of
      monoamine oxidase and catecholamine-O-methyltransferase, conjugation is a major
      route of metabolism. Glucuronide and sulfate conjugates of ritodrine are found in
      maternal urine. However, the structure of these metabolites has not been
      determined. The purpose of this study was to determine the structure of these
      conjugates. Urine from patients on ritodrine therapy was purified by QAE Sephadex
      ion exchange chromatography. The partially purified conjugates were derivatized
      and analyzed by GC/MS. The data did not indicate an exclusive site of
      conjugation. Analysis of both the glucuronide and sulfate conjugates indicates
      that either of the two phenolic hydroxyl groups may be involved in the formation
      of conjugated metabolites. However, conjugation of the [2-(p-hydroxyphenyl)-2
      hydroxy-1-methylethyl]amine phenolic hydroxyl is more prevalent for both
      conjugates. This phenolic hydroxyl group is unique since it is located on the
      portion of the ritodrine molecule which more closely resembles the structure of
      endogenous catecholamines.

PMID- 1976075
TI  - Inhibition of the metabolism of ethyl carbamate by acetaldehyde.
AB  - Ethyl carbamate is an animal carcinogen when administered in large doses; it is
      naturally present in minute concentrations in fermented foods and beverages.
      Previous studies from this laboratory have demonstrated that ethanol, in vivo,
      inhibits the metabolism of ethyl carbamate in mice, but the enzyme system has not
      been identified. In an effort to further characterize the enzyme system
      responsible, the metabolic products of ethanol metabolism were studied to
      determine whether ethanol or either of its metabolites is inhibitory.
      Acetaldehyde (400 mg/kg) is a potent inhibitor of ethyl carbamate metabolism for
      about 2 hr in vitro, but sodium acetate is not. Paraldehyde (250 mg/kg) has a
      slower onset and longer duration of inhibition, suggesting that its conversion to
      acetaldehyde produces the inhibitory molecule. Disulfiram (200 mg/kg) has a
      prolonged inhibitory effect; this effect is enhanced and extended when the
      disulfiram is combined with acetaldehyde (400 mg/kg). D-Penicillamine, given in a
      regimen of 1.2 g/kg 0.5 hr before and 0.6 g/kg 1.5 and 3.5 hr after ethyl
      carbamate, is not inhibitory; however, it abolishes the inhibitory effect of
      acetaldehyde, presumably from sequestration of acetaldehyde. These studies
      demonstrate that acetaldehyde is an inhibitor of the metabolism of ethyl
      carbamate and suggest that acetaldehyde is one, and perhaps the only, molecule
      responsible for the inhibition seen when ethanol is administered to mice. In
      vitro incubation studies determined that ethyl carbamate was not metabolized by
      human plasma.

PMID- 1976076
TI  - Radioimmunoassay of nicotine-delta 1'(5')-iminium ion, an intermediate formed
      during the metabolism of nicotine to cotinine.
AB  - Cotinine, one of the major metabolites of nicotine, is formed by two sequential
      enzyme reactions: [formula: see text] Chemical and immunological methods of
      analysis are available to quantify these two compounds (I and III). Study of the
      intermediate (III) is hampered because of its complex chemistry and lack of
      simple methods for its assay. Generally, (II) is trapped by addition of cyanide
      and analyzed as the 5'-cyanonicotine adduct. In order to develop an immunoassay
      for (II), rabbits were immunized with a 3'-succinylmethyl-5'-cyanonicotine
      protein conjugate with the expectation that (II) would, after treatment with
      cyanide, be quantified as 5'-cyanonicotine. Unexpectedly, however, the antibodies
      recognized the cyano adduct and (II) to the same extent (limit of deletion = 1.2
      pmol). Nicotine, cotinine, and several other metabolites do not significantly
      inhibit the antigen-antibody reaction. Inhibition studies with 5' substituted
      nicotine analogs indicate that the 5'-hydroxynicotine tautomer (IIb) is the
      species recognized by the antibodies. Inin vitro metabolic studies, (II)
      accumulates in the absence of aldehyde oxidase, but in its presence, is converted
      to cotinine. As judged by serological activity, dilute solutions (under 15
      microM) of (II) are stable when allowed to stand for 6 days at pH 7 and 37
      degrees C. However, at high concentrations of iminium ion (where NMR studies
      showed instability and formation of multiple products) serological activity is
      also lost. Iminium ions are generated during the metabolism of some tertiary
      amine xenobiotics. The use of alpha-cyanoamine haptens to elicit antibodies
      specific for iminium ions and/or their cyano adducts may permit development of
      immunoassays for these compounds.

PMID- 1976077
TI  - Biotransformation of halothane in guinea pig liver slices.
AB  - The biotransformation of halothane was studied using liver slices. Precision-cut
      Hartley male guinea pig liver slices (1 cm diameter; 250-300 microns thick) were
      incubated in sealed roller vials containing supplemented Krebs-Henseleit buffer
      at 37 degrees C under different O2 tensions (2.5, 21, and 95%). After a 1-hr
      preincubation, halothane was vaporized in the vial producing a 1.9 mM medium
      concentration. Halothane metabolites (Br-, trifluoroacetic acid, F-) were
      measured at 2, 4, and 6 hr. Viability of the incubated slices was verified by
      determining intracellular K+ content and levels of cytochrome P-450, which were
      maintained under 95% O2 atmosphere but decreased with lower O2 tensions (2.5%).
      The highest fluoride production was 300 +/- 22 pmol/mg slice weight/6 hr at low
      O2 tension (2.5%). Defluorination decreased with increasing O2 tension to
      undetectable levels under 95% O2. Production of the oxidative metabolite,
      trifluoroacetic acid, was highest at 95% O2 (2.35 +/- 0.17 nmol/mg slice weight/6
      hr). Trifluoroacetic acid production decreased with decreasing O2 tension. Br-
      production was the highest at 21% O2 (1.8 +/- 0.13 nmol/mg slice weight/6 hr).
      Production of Br- was not dependent on the O2 tension. The guinea pig slices are
      capable of biotransforming halothane (oxidative/reductive); therefore, this in
      vitro system appears suitable for studying the biotransformation of halothane.

PMID- 1976079
TI  - Morphologic changes and covalent binding of 1,1-dichloroethylene in Clara and
      alveolar type II cells isolated from lungs of mice following in vivo
      administration.
AB  - We have investigated the metabolism and covalent binding of 1,1-dichloroethylene
      (1,1-DCE) in isolated unseparated lung cells and in enriched fractions of Clara
      and alveolar type II cells from mice. Lung cells from control mice separated by
      centrifugal elutriation were viable and metabolically active as assessed by
      measurements of 7-ethoxycoumarin deethylase, NADPH cytochrome c reductase, and
      glutathione S-transferase activities, which were highest in fractions enriched in
      Clara cells. Mice were treated with [14C]1,1-DCE (125 mg/kg; 20 microCi/kg) in
      vivo and, 1 hr later, lung cells were isolated and binding of [14C]1,1-DCE
      determined. Covalent binding was highest in the Clara cell fraction (480 +/- 205
      pmol/10(6) cells; 41% Clara cell purity) when compared to the levels present in
      the fractions containing type II cells (126 +/- 63 pmol/10(6) cells; 51% type II
      cell purity) and mixed cells from whole lung (29 +/- 13 pmol/10(6) cells).
      Ultrastructurally, alveolar type II cells from lungs of control and 1,1-DCE
      treated mice exhibited normal morphology with well-preserved lamellar bodies.
      Whereas Clara cells isolated from lungs of control mice appeared structurally
      unimpaired, those from the lungs of 1,1-DCE-treated mice displayed severe damage
      and disruption of cellular organelles. The results of these experiments
      demonstrate the highest binding of [14C]1,1-DCE-metabolite(s) in Clara cells,
      whereas significantly lower binding was found in both alveolar type II and
      unseparated lung cells. The substantial binding of [14C]1,1-DCE in Clara cells
      correlated positively with the high monooxygenase capacity and the preferential
      damage sustained by this cell population.

PMID- 1976078
TI  - Studies on the metabolism and chiral inversion of ibuprofen in isolated rat
      hepatocytes.
AB  - The oxidative metabolism and chiral inversion of ibuprofen in freshly isolated
      rat hepatocytes was studied with the aid of a stereoselective GC/MS assay
      procedure. Hydroxylation of the isobutyl side chain at the subterminal carbon (to
      give hydroxyibuprofen) proved to be the major route of metabolism of both R(-)
      ibuprofen and S(+)-ibuprofen, while formation of the corresponding
      diastereoisomeric 2-methylpropionic acid derivatives (carboxyibuprofen) was of
      minor quantitative importance. Both oxidative pathways were inhibited in the
      presence of metyrapone, a cytochrome P-450 inhibitor. R(-)-Ibuprofen underwent
      metabolic chiral inversion to the S(+) enantiomer, whose formation was dependent
      on incubation time, cell density, and substrate concentration. S(+)-Ibuprofen, on
      the other hand, was not converted to R(-)-ibuprofen in rat hepatocytes. When
      cells were incubated with a mixture of unlabeled R(-)-ibuprofen and R(-)-[3,3,3
      2H3]ibuprofen, the resultant S(+) enantiomer consisted only of unlabeled and
      trideutero molecules (formed in the same ratio as the corresponding species of R(
      )-ibuprofen), indicating that 2,3-dehydroibuprofen did not serve as the
      symmetrical intermediate in the chiral inversion reaction. Collectively, these
      results demonstrate that freshly isolated rat hepatocytes represent a convenient
      and reproducible in vitro model system for studies on the metabolism and chiral
      inversion of ibuprofen.

PMID- 1976080
TI  - Unsubstituted amides: new class of potent inhibitors of human microsomal epoxide
      hydrolase.

PMID- 1976082
TI  - Isolation and characterization of an unusual glucuronide conjugate of
      rimantadine.

PMID- 1976081
TI  - Effects of carbon tetrachloride administration to guinea pigs on cytochromes P
      450 and antioxidant levels in the inner and outer zones of the adrenal cortex.

PMID- 1976083
TI  - Microsomal metabolism of the 1",1"-dimethylheptyl analogue of cannabidiol:
      relative percentage of monohydroxy metabolites in four species.

PMID- 1976084
TI  - [The pathology of insulinoma and gastrinoma. The location, size, multicentricity,
      association with multiple endocrine type-I neoplasms and malignancy].
AB  - The pathology of insulinoma and gastrinoma was studied in 81 patients (31 men, 50
      women, mean age 48.4 years) suffering from persistent hyperinsulinaemic
      hypoglycaemia, and in 44 patients (28 men, 16 women, mean age 48.5 years) with
      Zollinger-Ellison syndrome. Insulinomas were seen in the pancreas of all patients
      with persistent hyperinsulinaemic hypoglycaemia. In 70 of the 81 patients the
      insulinoma was solitary, whereas six patients had multiple insulinomas. In five
      patients with multiple endocrine neoplasia type I, multiple endocrine tumours of
      the pancreas were visible, only one of them in each case being an insulinoma. 75%
      of all insulinomas were less than 2 cm in size and 15% were malignant. 18 of the
      44 Zollinger-Ellison syndrome patients also had multiple endocrine neoplasia type
      I. Nine of these patients presented with duodenal gastrinomas which were often
      multiple and smaller than 0.5 cm. The gastrinoma was located in the pancreas of
      one of the patients with multiple endocrine neoplasia, in two patients in lymph
      nodes, and no gastrinoma was identified in the specimens from six patients. 33%
      of the duodenal gastrinomas had metastasised. Solitary gastrinomas were found in
      all 26 patients with sporadic Zollinger-Ellison syndrome, 14 being located in the
      pancreas (diameter over 2 cm in eight cases) and ten in the duodenum (diameter
      less than 1 cm in seven cases). 16 of these gastrinomas were malignant.

PMID- 1976085
TI  - Effects of ectopic expression of caudal during Drosophila development.
AB  - The effects of heat-shock-induced ectopic expression of the homeobox gene caudal
      (cad) at all stages of Drosophila development have been examined. Presence of cad
      protein (CAD) at the anterior end of cellular blastoderm embryos was found to
      disrupt head development and segmentation, due to alteration of the expression of
      segmentation genes such as fushi tarazu and engrailed, as well as repression of
      head-determining genes such as Deformed. These results support the conclusion
      that, while CAD is probably required to activate transcription of fushi tarazu in
      the posterior half of the embryo, it should not be expressed in the anterior half
      prior to gastrulation, and thus suggest a role for the CAD gradient. Ectopic
      expression of CAD at later stages of development has no obvious effects on
      embryogenesis or imaginal disc development, suggesting that the homeotic genes of
      the Antennapedia and Bithorax Complexes are almost completely epistatic to
      caudal.

PMID- 1976086
TI  - Expression of a homeobox gene product in normal and mutant zebrafish embryos:
      evolution of the tetrapod body plan.
AB  - An antibody was used to detect antigens in zebrafish that appear to be homologous
      to the frog homeodomain-containing protein XlHbox 1. These antigens show a
      restricted expression in the anteroposterior axis and an anteroposterior gradient
      in the pectoral fin bud, consistent with the distribution of XlHbox 1 protein in
      frog and mouse embryos. In the somitic mesoderm, a sharp anterior limit of
      expression coincides exactly with the boundary between somites 4 and 5, and the
      protein level fades out posteriorly. A similar, graded expression of the antigen
      is seen within the series of Rohon-Beard sensory neurons of the CNS. We also
      immunostained the mutant spt-1 ('spadetail'), in which the trunk mesoderm is
      greatly depleted and disorganized in the region of XlHbox 1 expression. The
      defects stem from misdirected cell movements during gastrulation, but
      nervertheless, newly recruited cells that partially refill the trunk mesoderm
      express the antigen within the normal span of the anteroposterior axis. This
      finding suggests that the mutation does not delete positional information
      required for activation of the XlHbox 1 gene.

PMID- 1976087
TI  - Expression and function of the homoeotic genes Antennapedia and Sex combs reduced
      in the embryonic midgut of Drosophila.
AB  - Drosophila homoeotic genes control the formation of external morphological
      features of the embryo and adult, and in addition affect differentiation of the
      nervous system. Here we describe the morphogenetic events in the midgut that are
      controlled by the homoeotic genes Sex combs reduced (Scr) and Antennapedia
      (Antp). The midgut is composed of two cell layers, an inner endoderm and an outer
      visceral mesoderm that surround the yolk. Scr and Antp are expressed in the
      visceral mesoderm but not in the endoderm. The two genes are required for
      different aspects of the midgut morphogenesis. In Scr null mutant embryos the
      gastric caeca fail to form. Scr is expressed in the visceral mesoderm cells
      posterior to the primordia of the gastric caeca and appears to be indirectly
      required for the formation of the caeca. Antp is expressed in visceral mesoderm
      cells that overlie a part of the midgut where a constriction will form, and Antp
      null mutant embryos fail to form this constriction. An ultrastructural analysis
      of the midgut reveals that the visceral mesoderm imposes the constriction on the
      endoderm and the yolk. The mesodermal tissue contracts within the constriction
      and thereby penetrates the layer of the midgut endoderm. Microtubules participate
      in the morphological changes of the visceral mesoderm cells. The analysis of the
      expression of Scr in Antp mutant embryos revealed a case of tissue-specific
      regulation of Scr expression by Antp. In the epidermis, Antp has been shown to
      negatively regulate Scr, but it positively regulates Scr in the visceral
      mesoderm.

PMID- 1976088
TI  - Mouse Hox-3.4: homeobox sequence and embryonic expression patterns compared with
      other members of the Hox gene network.
AB  - A putative mouse homeobox gene (Hox-3.4) was previously identified 4kb downstream
      of the Hox-3.3 (Hox-6.1)* gene (Sharpe et al. 1988). We have now sequenced the
      Hox-3.4 homeobox region. The predicted amino acid sequence shows highest degree
      of homology in the mouse with Hox-1.3 and -2.1. This, together with similarities
      in the genomic organisation around these three genes, suggests that they are
      comembers of a subfamily, derived from a common ancestor. Hox-3.4 appears to be a
      homologue of the Xenopus Xlhbox5 and human cp11 genes (Fritz and De Robertis,
      1988; Simeone et al. 1988). Using a panel of mouse-hamster somatic cell hybrids
      we have mapped the Hox-3.4 gene to chromosome 15. From the results of in situ
      hybridization experiments, we describe the distribution of Hox-3.4 transcripts
      within the 12 1/2 day mouse embryo, and we compare this with the distributions of
      transcripts shown by seven other members of the Hox gene network. We note three
      consistencies that underlie the patterns of expression shown by Hox-3.4. First,
      the anterior limits of Hox-3.4 transcripts in the embryo are related to the
      position of the Hox-3.4 gene within the Hox-3 locus. Second, the anterior limits
      of Hox-3.4 expression within the central nervous system are similar to those
      shown by subfamily homologues Hox-2.1 and Hox-1.3, although the tissue-specific
      patterns of expression for these three genes show many differences. Third, the
      patterns of Hox-3.4 expression within the spinal cord and the testis are very
      similar to those shown by a neighbouring Hox-3 gene (Hox-3.3), but they are quite
      different from those shown by Hox-1 genes (Hox-1.2, -1.3 and -1.4).

PMID- 1976089
TI  - Structure and expression of the mouse Oct2a and Oct2b, two differentially spliced
      products of the same gene.
AB  - A large family of tissue-specific nuclear proteins interact with the octamer
      motif ATTTGCAT, a transcriptional regulatory element found in the promoter and
      enhancer sequences of many genes. As a step towards elucidating the mechanism of
      this regulation, cDNA clones of the mouse Oct2 protein were isolated. One, called
      here Oct2b, encodes a larger variant of the previously described Oct2a proteins.
      The Oct2b cDNA has an insertion of 74 bp close to the 3' end which creates an
      open reading frame distinct from Oct2a. As a result, the Oct2b protein has a
      carboxy end which is similar to that of the ubiquitous octamer-binding protein
      Oct1. Analysis of the Oct2 gene shows that Oct2a and Oct2b are differentially
      spliced products of the same gene. The insertion in the Oct2b cDNA results from
      the inclusion of an additional exon in the mRNA which would otherwise reside in
      an intron sequence of the Oct2a transcript. RNA analysis demonstrates that both
      Oct2a and 2b mRNAs are most abundant in B-cells but they are also expressed in a
      variety of tissues including brain, intestine, testis, kidney, as well as in
      embryos. Interestingly, the ratio of Oct2a and 2b varies among tissues. In situ
      hybridization studies during mouse embryogenesis show that the Oct2 gene is
      widely expressed in the developing nervous system. In contrast, expression in the
      adult brain is confined to very specific areas which include the suprachiasmatic
      and medial mammillary nuclei, hippocampus, olfactory tract and the olfactory
      bulb. Oct2 proteins are present in both neuronal and oligodendroglial cells,
      although they are more abundant in glial cells.

PMID- 1976090
TI  - Different patterns of transcription from the two Antennapedia promoters during
      Drosophila embryogenesis.
AB  - The homeotic genes of Drosophila control the differentiation of segments during
      development. Mutations in these genes cause one or more segments to develop
      structures normally found elsewhere in the organism. Several studies have shown
      that the spatial patterns of homeotic gene transcription are highly complex, and
      that these precise patterns of transcription are critical to normal development.
      The homeotic gene Antennapedia (Antp), a member of the Antennapedia Complex, is
      required for the correct differentiation of thoracic segments in both embryos and
      adults. The patterns of total Antp transcript and protein accumulation have been
      described in detail, but the contribution of each promoter to the overall pattern
      in embryos has not been reported. We have examined in detail the spatial
      distribution of transcripts from each of the Antp promoters in both embryo
      sections and whole embryos by in situ hybridization using promoter-specific
      probes. We show that the transcripts from each of the two promoters accumulate in
      distinct, but overlapping patterns during embryogenesis. The results demonstrate
      that the two Antp promoters are differentially regulated in embryos and provide a
      basis for examining the regulation of the two promoters and characterizing more
      fully the function of Antp during embryogenesis. In addition, we have examined
      the regulation of each of the Antp promoters by genes of the bithorax complex (BX
      C). We show that in BX-C- embryos both promoters are derepressed in the abdomen.

PMID- 1976091
TI  - Secretion and degradation of glucagon by HIT cells.
AB  - HIT cells have been widely used to study synthesis and secretion of insulin. It
      has been assumed that this cell line secretes no other islet hormones. To
      ascertain whether HIT cells synthesize, secrete, and degrade glucagon, we
      examined cell extracts for this peptide and compared secretion and degradation of
      glucagon and insulin during stimulation of the cells by arginine. Glucagon levels
      in acid extracts of HIT cells were found to be 0.72 +/- 0.15 pmol/mg protein.
      Both glucagon and insulin were maximally stimulated in a glucagon/insulin molar
      ratio of 0.029 by arginine concentrations of 25-50 nM, and the concentration of
      arginine that provided half-maximum responses for both hormones was approximately
      3 mM. Diminution of arginine-induced glucagon secretion was caused by
      somatostatin, a physiological inhibitor of pancreatic islet alpha-cell function.
      HPLC was used to authenticate the glucagon levels stimulated by arginine for 60
      min and measured by RIA. Thirty-six percent of immunoreactive glucagon was found
      in the fractions representing authentic glucagon, whereas the remaining 64%
      eluted earlier. Experiments examining the fate of radiolabeled glucagon exposed
      to HIT cells revealed time-dependent degradation of the radioisotope to earlier
      eluting forms, which accounted for approximately 50% of the radioactivity by 60
      min and was complete by 18 h, indicating that the early peak detected by RIA
      represented a metabolite of glucagon. Radioisotopic insulin was degraded more
      slowly with an apparent half-life of approximately 36 h. We conclude that HIT
      cells are not only able to synthesize, secrete, and degrade insulin, but also
      much smaller amounts of glucagon.

PMID- 1976092
TI  - Deprivation of growth hormone-releasing hormone early in the rat's neonatal life
      permanently affects somatotropic function.
AB  - This work investigated in rats whether passive immunization against the
      endogenous GHRF in the early postnatal period led to permanent alterations of
      somatotropic function, similar to those observed in several human growth
      disorders, e.g. constitutional growth delay (CGD). On postnatal days 1, 2, 4, 6,
      8, and 10, rats were given an anti-GHRF-serum (GHRH-Ab, 100 microliters/rat, sc)
      and were tested 1, 30, and 60 days after this treatment for basal and GHRH
      stimulated GH secretion both in vivo and in vitro. GHRH-Ab reduced both basal and
      GHRF-stimulated GH secretion at all intervals and induced marked and chronic
      impairment of growth rate. The following differences were observed in the GHRH-Ab
      treated rats compared to normal rabbit serum-treated controls: 1) GH biosynthesis
      (incorporation of L-[3H]leucine into the electrophoretic band of GH): reduction
      of about 70%, 1 day but not 30 days after treatment; 2) Pituitary weight:
      significant reduction in absolute weight (30-40%) at all posttreatment intervals,
      and relative weight, 1 and 30 days after treatment. 3) Pituitary GH
      concentration: significant reduction in GH content (about 40%) but not
      concentration, at all posttreatment intervals; 4) Percentage of somatotrophs
      (immunocytochemistry): about 40% reduction 1 day, but not 30 and 60 days after
      treatment; 5) Hypothalamic somatostatin messenger RNA (mRNA) levels in situ
      hybridization): selective reduction (40%) in the periventricular nucleus 1 day
      but not 30 days after treatment; 6) Hypothalamic somatostatin cell number
      (immunocytochemistry): no significant changes in any hypothalamic area at any
      interval; 7) Pituitary somatostatin binding (in situ autoradiography):
      significant reduction, 1 day and 30 days after treatment; 8) Somatostatin
      inhibition of GH release "in vitro": somatostatin effect on GH release was
      reduced 30 days after treatment. These and previous data indicate that: 1)
      Transient deprivation of GHRF in the immediate postnatal period of the rat leads
      to permanent impairment of growth rate and somatotropic function; 2) GHRF
      deficiency itself or through reduction of GH secretion impairs somatostatin
      functions temporarily in the hypothalamus and permanently in the pituitary; 3)
      This rat model may mimic some forms of growth disorders in humans and holds
      promise as useful tools for investigating the underlying pathophysiological
      mechanisms.

PMID- 1976093
TI  - Endotoxin-induced release of interleukin-6 from rat medial basal hypothalami.
AB  - Interleukin-6 (IL-6) is an inflammatory cytokine that stimulates T-cell
      activation and B-cell differentiation. We recently reported that picomolar
      concentrations of IL-6 stimulated PRL, GH, and LH release in vitro. These data
      suggested that IL-6 may function as a hypothalamic releasing factor for anterior
      pituitary hormones. Medial basal hypothalami (MBH) were incubated for 60-90 min
      in Krebs-Ringer bicarbonate buffer supplemented with 0.025% BSA, and the
      conditioned medium was assayed for IL-6 concentrations by the 7TD1 cell growth
      factor assay. It was found that MBH released IL-6 in vitro. Although depolarizing
      concentrations of K+ (56 mM) did not increase IL-6 release, somatostatin release
      from the MBH was increased significantly. The bacterial endotoxin
      lipopolysaccharide (LPS; 1-100 ng/ml) induced significant increases in IL-6
      release from the MBH. The presence of IL-6 in the hypothalamus suggested a
      possible role for this cytokine in the regulation of neuropeptide release;
      however, the release of somatostatin was not affected by 20 ng/ml IL-6.
      Comparison studies of neural and neuroendocrine tissues revealed that the
      anterior and posterior pituitaries released larger amounts of bioactive IL-6 than
      the MBH or parietal cortex during a 4-h incubation; induction of IL-6 release by
      endotoxin occurred only in the anterior pituitary and hypothalamus. IL-6 mRNA was
      detectable in the MBH and anterior pituitary tissue after a 4-h incubation;
      however, no IL-6 mRNA was detectable in freshly isolated tissues. LPS (100 ng/ml)
      and (Bu)2cAMP (1 mM) increased IL-6 mRNA accumulation in and IL-6 release from
      the MBH and anterior pituitary. These data suggest that the MBH synthesizes and
      releases IL-6 via a nonneuronal source in vitro.

PMID- 1976094
TI  - Studies of the regulation of the hypothalamic-pituitary-adrenal axis in sheep
      with hypothalamic-pituitary disconnection. II. Evidence for in vivo ultradian
      hypersecretion of proopiomelanocortin peptides by the isolated anterior and
      intermediate pituitary.
AB  - Studies were performed to determine whether the isolated ovine anterior and
      intermediate pituitary might rhythmically secrete three POMC peptides, ACTH, ir
      beta-endorphin (ir-beta-EP), and ir-alpha-melanocyte stimulating hormone (ir
      alpha-MSH) in vivo. When blood was taken at 10-min intervals from four ewes with
      hypothalamo-pituitary-disconnection (HPD), a distinct POMC-peptide and cortisol
      ultradian rhythm was noted. A comparison of the four HPD ewes with five
      nonstressed hypothalamopituitary-intact (HPI) ewes revealed that the mean plasma
      levels of the three POMC-peptides and cortisol were increased, the mean ACTH and
      ir-alpha-MSH pulse amplitudes were increased, and the mean ir-beta-EP and ir
      alpha-MSH interpulse intervals were decreased. When four HPI ewes were subjected
      to a mild stress, plasma POMC-peptide and cortisol levels increased significantly
      when compared with the five unstressed HPI animals. In addition, the ACTH and
      cortisol pulse amplitudes increased and the ir-beta-EP and ir-alpha-MSH
      interpulse intervals decreased. Although plasma ACTH levels in the stressed HPI
      and HPD ewes were comparable, mean plasma cortisol levels were 2-fold greater in
      the stressed HPI animals. To determine whether the ACTH hypersecretion in the HPD
      ewe might reflect a net reduction in hypothalamic inhibitory influence over ACTH
      secretion, we examined the effects of dopamine (DA), somatostatin (SS-14), and
      rat atrial natriuretic peptide [rANF(1-28)] on the secretion of ACTH from
      cultured ovine anterior pituitary cells. DA and SS-14 did not exert a discernible
      effect on basal, CRF-, or arginine vasopressin (AVP)-stimulated ACTH secretion.
      Although basal ACTH secretion was unaffected by rANF(1-28) (10(-12)-10(-8) M), a
      significant inhibition of CRF- and AVP-stimulated ACTH release was
      observed.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1976095
TI  - Pulsed dye laser in the treatment of 325 calculi of the urinary tract.
AB  - The pulsed dye laser (Candela) has been used from February 1988 to September 1989
      in order to treat 325 stones in 278 patients. A total of 285 endoscopies has been
      performed. The pulsed laser has helped to achieve the fragmentation of 318
      stones. Laser fragmentation has not induced any complication at all. The main
      failures can be attributed to the nature and shape of the stone. Thanks to the
      thin laser fiber, the use of small diameter ureteroscopes has increased the
      reliability of ureteroscopy. The use of this technique combined to extracorporeal
      shock wave lithotripsy (ESWL) has reduced the rate of open surgery for ureteral
      stones down to less than 1%.

PMID- 1976096
TI  - GBR 12909 reverses the SCH 23390 inhibition of rewarding effects of brain
      stimulation.
AB  - Curve-shift was used to test the effect of SCH 23390, a dopamine D1 receptor
      antagonist, and GBR-12909, a selective dopamine uptake blocker, on self
      stimulation behavior. GBR 12909 (8 mg/kg) produced a significant decrease in self
      stimulation threshold when administered alone, and reversed the increase in
      threshold produced by SCH 23390 (0.08 mg/kg). The reversal of the SCH 23390
      effect by GBR 12909 suggests that the inhibition of self-stimulation produced by
      SCH 23390 is due to blockade of dopamine receptors.

PMID- 1976097
TI  - Spinal antinociceptive effects of excitatory amino acid antagonists: quisqualate
      modulates the action of N-methyl-D-aspartate.
AB  - Blockade of N-methyl-D-aspartate (NMDA) receptors in the spinal cord of rodents
      has been shown to produce antinociceptive effects and motor impairment. To find
      out whether other receptors for excitatory amino acids (EAA) can influence spinal
      pathways utilizing the NMDA receptors we compared, in mice, the behavioral
      consequences of intrathecal injection of four EAA antagonists, 2-amino-5
      phosphono valerate (APV), kynurenate, gamma-D-glutamyl glycine (DGG) and
      glutamylaminomethyl sulphonate (GAMS). The selectivity of these antagonists at
      different concentrations was evaluated behaviorally by assessing their ability to
      block the biting behavior elicited by intrathecal EAA agonists. Blockade of the
      NMDA receptor was necessary to elicit antinociceptive effects and motor
      impairment. Thus, APV produced antinociception at concentrations selective for
      the action of NMDA. The wide spectrum EAA antagonists, DGG and kynurenate, and
      the quisqualate/kainate antagonist, GAMS, all produced antinociception and motor
      impairment at concentrations which also blocked NMDA-induced bites. However, an
      inhibitory modulation of the action of NMDA by quisqualate-sensitive systems was
      also observed. Thus, high concentrations of APV (greater than 1 mM), which also
      blocked quisqualate-elicited bites, produced a surprising, sharp decrease in APV
      antinociception and motor impairment, effects which were reversed by quisqualate.
      Furthermore, quisqualate significantly inhibited NMDA-induced bites. Additional
      evidence for such an inhibitory-modulatory effect of quisqualate can be gathered
      from the antinociceptive potency of DGG. This antagonist, which blocks the action
      of both NMDA and quisqualate, was less potent as an antinociceptive agent than
      APV. No such discrepancy between the ability to inhibit the action of NMDA and to
      elicit antinociceptive effects and motor impairment was noted for either
      kynurenate or GAMS. Evidence is provided that these different profiles of action
      are due to the fact that DGG and high concentrations of APV act at different
      subpopulations of quisqualate receptors than do kynurenate and GAMS, and that the
      former subpopulation is involved in the modulation of the action of NMDA.

PMID- 1976098
TI  - Electrophysiological characterization of a novel potent and orally active NMDA
      receptor antagonist: CGP 37849 and its ethylester CGP 39551.
AB  - The selectivity and potency of the novel competitive N-methyl-D-aspartate (NMDA)
      receptor antagonists, CGP 37849 and CGP 39551, were investigated in vitro and in
      vivo using electrophysiological approaches. Like the reference blocker DL-AP5,
      both compounds acted in vitro (hippocampus, substantia nigra, spinal cord) to
      antagonize the excitatory actions of exogenously administered NMDA as well as the
      synaptically elicited, physiological NMDA receptor responses in hippocampus and
      spinal cord. In all isolated preparations CGP 37849 was more potent than CGP
      39551, and 5- to 10-fold more potent than DL-AP5. Neither compound showed any
      marked effect on responses evoked by quisqualate and kainate. NMDA excited
      dopaminergic cells in the pars compacta region of the substantia nigra in a
      concentration-dependent manner. This effect also could be selectively antagonized
      by CGP 37849 and CGP 39551. In the anaesthetized rat, excitatory responses of
      hippocampal pyramidal cells evoked by iontophoretic application of NMDA were
      antagonized by CGP 37849 and CGP 39551 following their oral administration
      without reducing quisqualate or kainate responses. In contrast to the in vitro
      situation, CGP 39551 was more potent than CGP 37849 in vivo. Effective doses were
      30 mg/kg p.o. for CGP 39551 and 100 mg/kg p.o. for CGP 37849. In conclusion, it
      is demonstrated that CGP 37849 and CGP 39551 selectively antagonize NMDA evoked
      neuronal responses in vivo and in vitro and that the drugs are centrally active
      following their oral administration.

PMID- 1976100
TI  - The 18S ribosomal RNA sequence of the sea anemone Anemonia sulcata and its
      evolutionary position among other eukaryotes.
AB  - Evolutionary trees based on partial small ribosomal subunit RNA sequences of 22
      metazoa species have been published [(1988) Science 239, 748-753]. In these
      trees, cnidarians (Radiata) seemed to have evolved independently from the
      Bilateria, which is in contradiction with the general evolutionary view. In order
      to further investigate this problem, the complete srRNA sequence of the sea
      anemone Anemonia sulcata was determined and evolutionary trees were constructed
      using a matrix optimization method. In the tree thus obtained the sea anemone and
      Bilateria together form a monophyletic cluster, with the sea anemone forming the
      first line of the metazoan group.

PMID- 1976099
TI  - Hepatic zonation of insulin-stimulated tyrosine phosphorylation.
AB  - Zonal distribution of insulin stimulation of hepatic protein tyrosine
      phosphorylation, detected by immunoblotting with an anti-phosphotyrosine
      antibody, has been studied in the in situ perfused rat liver by dual-digitonin
      pulse perfusion. Insulin promotes the rapid and sustained tyrosine
      phosphorylation of two proteins (pp150 and pp69) that are present only in the
      perivenous hepatocytes, while three others (pp46, pp48 and pp96) are stimulated
      identically in the periportal and perivenous cells. The ability of insulin to
      rapidly activate acetyl-CoA carboxylase is indistinguishable between the hepatic
      zones. Hepatic zonation of insulin-stimulated tyrosine phosphorylation could
      underly differential hepatic insulin responses and might provide clues to the
      identification of tyrosine phosphorylated proteins linked to insulin regulation
      of intracellular events.

PMID- 1976102
TI  - Porcine pancreastatin has no effect on endocrine secretion from the pig pancreas.
AB  - We investigated the effects of porcine pancreastatin on the endocrine and
      unstimulated exocrine secretion of isolated, perfused porcine pancreas.
      Pancreastatin in a concentration of 10(-8) mol/l had no effect on basal secretion
      of insulin, glucagon and somatostatin at a perfusate glucose concentration of 5
      mmol/l (n = 4) and neither at 10(-8) nor 10(-7) mol/l influenced the hormone
      responses to acute elevations of perfusate glucose concentration from 3.5 to 11
      mmol/l (n = 7). This elevation strongly stimulated insulin secretion and
      inhibited glucagon secretion. Exocrine secretion was not affected by
      pancreastatin. The results suggest that pancreastatin does not directly influence
      pancreatic secretion.

PMID- 1976101
TI  - Identification of susceptibility loci for type 1 (insulin-dependent) diabetes by
      trans-racial gene mapping.
AB  - A major component of inherited susceptibility to Type 1 (insulin-dependent)
      diabetes mellitus has been mapped to the major histocompatibility complex.
      Certain gene alleles in this region determine susceptibility and resistance to
      the disease. Mapping of susceptibility is hindered by the limitations of
      conventional tissue typing techniques, and by strong linkage disequilibrium
      within this part of the genome. Recombinant DNA technology and trans-racial
      studies have been used to allow finer mapping of genetic predisposition to Type 1
      diabetes. These techniques have localised alleles encoding susceptibility and
      resistance to the DQ region. Other alleles determining disease susceptibility
      remain poorly localised.

PMID- 1976104
TI  - Neuroscience and oncology. A unified view.
AB  - Evidence has been produced that the neoplastic event is the result of a multistep
      multifactorial process involving virtually every functional system within the
      organism. Traditional concepts such as cellular autonomy, uncontrolled growth and
      monoclonality of cancer are revised in the light of current data.
      Microenvironmental stimuli appear to affect relevant cancer cell functions,
      including locomotion, differentiation and gene expression. The complex
      interconnection between biological functions and messages, relevant among which
      are nervous inputs, requires the identification of new physiological models if
      the neoplastic process is to be understood.

PMID- 1976103
TI  - Cloning and expression of a cDNA encoding mouse kidney D-amino acid oxidase.
AB  - A cDNA encoding D-amino acid oxidase (DAO;EC1.4.3.3) has been isolated from a
      BALB/c mouse kidney cDNA library by hybridization with the cDNA for the porcine
      enzyme. Analysis of the nucleotide (nt) sequence of the clone revealed that it
      has a 1647-nt sequence with a 5'-terminal untranslated region of 68 nt, an open
      reading frame of 1035 nt that encodes 345 amino acids (aa), and a 3'-terminal
      untranslated region of 544 nt that contains the polyadenylation signal sequence,
      ATTAAA. The deduced aa sequence showed 77 and 78% aa identity with the porcine
      and human enzymes, respectively. Two catalytically important aa residues, Tyr228
      and His307, of the porcine enzyme, were both conserved in these three species.
      RNA blot hybridization analysis indicated that a DAO mRNA, of 2 kb, exists in
      mouse kidney and brain, but not liver. Synthesis of a functional mouse enzyme in
      Escherichia coli was achieved through the use of a vector constructed to insert
      the coding sequence of the mouse DAO cDNA downstream from the tac promoter of
      plasmid pKK223-3, which was designed so as to contain the lac repressor gene
      inducible by isopropyl-beta-D-thiogalactopyranoside. Immunoblot analysis
      confirmed the synthesis and induction of the mouse DAO protein, and the molecular
      size of the recombinant mouse DAO was found to be identical to that of the mouse
      kidney enzyme. Moreover, the maximum activity of the mouse recombinant DAO was
      estimated to be comparable with that of the porcine DAO synthesized in E. coli
      cells.

PMID- 1976105
TI  - Somatostatin and acute variceal hemorrhage.

PMID- 1976106
TI  - Acute variceal bleeding: still searching for the right treatment.

PMID- 1976107
TI  - The European experience with use of clozapine.
AB  - The efficacy and adverse effects of clozapine for patients who cannot be treated
      with conventional neuroleptics were evaluated by means of a retrospective chart
      review. The review showed that 85 percent of 503 inpatients experienced slight to
      nearly complete reduction in symptoms. Adverse effects occurred in 59 percent of
      patients, although only 7 percent had side effects severe enough to warrant
      discontinuation of the drug. Data for 70 outpatients treated with clozapine
      showed that the rate of rehospitalization was significantly lower than before
      treatment with the drug. These findings agree with those of other European
      studies and suggest that when hematological and other variables are carefully
      controlled, the benefits of clozapine therapy outweigh the risks.

PMID- 1976109
TI  - Glycaemic effects of tentacle extract of the jellyfish Acromitus rabanchatu
      (Annandale).
AB  - Tentacle extract of the common jellyfish A. rabanchatu, caused glycaemic
      alteration in fasting rabbits. Intravenous administration of the extract produced
      a significant rise followed by a significant fall in blood sugar level. Glucose
      tolerance in rabbits was also significantly increased. Extract-mediated
      hypoglycaemic response was fully abolished in alloxan diabetic rabbits.
      Preliminary separation on Sephadex G 50 indicated the hypoglycaemic factor to be
      a non-lethal protein of molecular weight less than 20 kDa. Heat treatment of
      extract and G 50 separated fraction P2 demonstrated total loss of hypoglycaemic
      activity.

PMID- 1976108
TI  - Who should perform the AIMS examination?
AB  - Psychiatrists and nonphysician mental health professionals working in community
      mental health centers have difficulty establishing the scope of their expertise,
      defining the limits of their roles, delegating responsibility, and sharing
      professional liability. The clinical, political, and administrative aspects of
      these tensions are examined in the context of arguments for and against
      physicians' delegating to nonphysician mental health professionals the task of
      screening CMHC patients for tardive dyskinesia using the Abnormal Involuntary
      Movement Scale. In 43 percent of mental health centers in Massachusetts surveyed
      by the authors, nonphysicians perform tardive dyskinesia screening. The authors
      suggest that the benefits of involving nonphysicians in tardive dyskinesia
      screening in the CMHC setting outweight the disadvantages.

PMID- 1976110
TI  - Possible prostaglandin-dopamine interactions during experimental gastric ulcer
      formation.
AB  - The effects of dopamine (DA) agonists and antagonists were investigated on
      indomethacin--and restraint stress (6 hr at RT)--induced gastric ulcer formation
      in rats. The DA-agonists, apomorphine and bromocryptine (both at 5 mg/kg)
      significantly attenuated the frequency and severity of gastric mucosal lesions in
      both experimental models. The DA-antagonist, haloperidol (0.05 and 1.0 mg/kg)
      aggravated the gastric ulcerogenesis of both indomethacin and stress, the effects
      with the lower dose being statistically significant. Haloperidol (0.05 mg/kg)
      also prevented the cytoprotective effects of apomorphine on indomethacin-ulcers.
      The atypical DA-antagonist, sulpiride (10 and 50 mg/kg), however, showed
      differential dose- and model-specific effects. Whereas, the lower dose attenuated
      indomethacin-ulcers, the higher dose (50 mg/kg) tended to aggravate this
      phenomenon. The trend of results were reversed in the restraint stress model.
      Indomethacin (1 mg/kg) aggravated stress-ulcers, an effect which was also
      appreciably neutralised by apomorphine (5 mg/kg) pretreatment. These results are
      discussed in light of possible prostaglandin-DA interactions during such
      experimental gastric pathology.

PMID- 1976111
TI  - Centrally mediated alpha & beta adrenoceptors controlling blood pressure in
      rabbits.
AB  - The effect of intracerebroventricular (icv) injection of noradrenaline (NA) on
      the blood pressure was studied in anaesthetised rabbits. Adrenoceptor blockers
      were used to study the specific adrenoceptor mediating the response. The results
      indicated a hypotensive response to icv injection of NA. This hypotensive
      response to NA was blocked by alpha-2 (yohimbine) and beta-1 (metoprolol) but not
      by alpha-1 (prazosin) and beta-2 (butoxamine) adrenoceptor blockers.

PMID- 1976112
TI  - Presence of K88-specific receptors in porcine ileal mucus is age dependent.
AB  - Ileal mucus and epithelial cells were isolated from newborn piglets that had
      never been fed and 35-day-old unweaned piglets. Both newborn and 35-day-old
      piglet mucus preparations supported growth of Escherichia coli Bd 1107/75 08, a
      K88-fimbriated porcine enterotoxigenic strain, equally well (i.e., generation
      times of 28 min were observed in both cases). Adhesion of E. coli Bd 1107/75 08
      to 35-day-old piglet ileal epithelial cells was, at most, 2 times that of the
      same strain to newborn piglet ileal epithelial cells; however, adhesion of E.
      coli Bd 1107/75 08 to 35-day-old piglet ileal mucus was 16 times that of the same
      strain to newborn piglet ileal mucus. The receptor in 35-day-old piglet ileal
      mucus was K88 specific, since it could be removed by purified K88ab fimbriae.
      Furthermore, adhesion of E. coli Bd 1107/75 08 to 35-day-old piglet ileal mucus
      was blocked by PAB10, a K88ab-, K88ac-, K88ad-specific monoclonal antibody.
      Although E. coli Bd 1107/75 08 traversed both newborn and 35-day-old piglet ileal
      mucus about equally well in vitro and bound well to underlying ileal epithelial
      cells after passing through newborn ileal mucus, it did not bind to ileal
      epithelial cells after passing through 35-day-old piglet ileal mucus. The data
      are discussed with respect to the role that K88-specific receptors present in
      newborn and ileal mucus might play in the pathogenesis of porcine enterotoxigenic
      E. coli strains which bear K88 fimbriae.

PMID- 1976114
TI  - Immunization of mice against Plasmodium vinckei with a combination of attenuated
      Salmonella typhimurium and malarial antigen.
AB  - Infection with the blood stage of the malaria parasite Plasmodium vinckei is
      uniformly lethal in mice. We found that immunization of BALB/c mice with a
      combination of killed P. vinckei antigens and an attenuated (aroA) Salmonella
      typhimurium strain induces high levels of protection against challenge with live
      P. vinckei. This is especially significant because, in our previous studies,
      immunization of mice with killed P. vinckei antigens and adjuvants such as
      Bordetella pertussis, complete Freund adjuvant, and saponin failed to induce
      protective immunity. Immunization with attenuated S. typhimurium alone did not
      provide any nonspecific immunity. In vivo depletion of CD4+ T cells in the mice
      immunized with attenuated S. typhimurium and P. vinckei antigens caused the loss
      of their immunity. Expression of this immunity required the presence of a spleen.
      These results support our previous hypothesis that a blood stage malaria vaccine
      may need both induction of CD4+ T cells specific for the parasite and
      modification of the spleen with a vaccine vehicle. Therefore, attenuated
      Salmonella strains such as the one used in this study, when expressing
      recombinant malarial antigens, might fulfill this requirement.

PMID- 1976113
TI  - Tissue-binding affinity of Proteus mirabilis fimbriae in the human urinary tract.
AB  - Binding characteristics of the two major fimbrial hemagglutinin types of
      uropathogenic Proteus mirabilis were determined in frozen sections of human
      kidney and in exfoliated uroepithelial cells. P. mirabilis 3087, which expresses
      the MR/P fimbriae, adhered avidly to the tubular epithelial cells of the kidney
      and also to the epithelial cells of urinary sediment. No adhesion to glomerular
      or peritubular elements of the kidney was detected. Indirect immunogold silver
      staining also showed that the purified MR/P fimbriae recognized the same kidney
      domains. Adhesion of strain 3087 to uroepithelial cells was completely inhibited
      by Fab fragments of antibodies against the purified MR/P fimbriae. A completely
      different tissue-binding pattern was exhibited by the MR/K fimbriae of P.
      mirabilis 2456. In the kidney, the MR/K fimbriae bound strongly to the Bowman's
      capsule of the glomeruli and to the tubular basement membranes. A weak binding to
      glomerular mesangium and tubular epithelial cells was also seen. Strain 2456 did
      not adhere to epithelial cells of urinary sediment. Analysis of normal human
      urine showed that it contains low-molecular-weight molecules capable of
      inhibiting the binding of the MR/P fimbriae; no urinary inhibitors could be
      detected for the MR/K fimbriae. Poor in vivo binding capacity to intact human
      uroepithelial cells may be an important factor in explaining the relatively low
      pathogenicity of P. mirabilis in healthy hosts.

PMID- 1976115
TI  - Genetically engineered S and F1C fimbriae differ in their contribution to
      adherence of Escherichia coli to cultured renal tubular cells.
AB  - Escherichia coli K-12 strains producing S-fimbrial adhesins, F1C fimbriae, and
      mutagenized fimbriae were tested in a binding assay with a renal tubular cell
      line. S-fimbrial adhesins and F1C fimbriae mediated binding to tubular cells. The
      SfaA, SfaG, and SfaS subunits of S fimbriae contributed to attachment. Site
      specific mutations in the sfaS gene reduced binding. The inhibition profile of
      F1C fimbriae resembled that of S fimbriae.

PMID- 1976116
TI  - Effect of type 1 piliation on in vitro killing of Escherichia coli by mouse
      peritoneal macrophages.
AB  - Escherichia coli K-12 mutants possessing defined lesions affecting type 1 pilus
      production, receptor binding, or length were examined for their ability to resist
      killing by mouse peritoneal macrophages in vitro. Mutants were mixed pairwise at
      known ratios in wells containing macrophages, and after incubation, the ratio of
      the survivors was assayed. The difference in phagocytic killing between type 1
      piliated cells and isogenic nonpiliated cells was significant, the piliated cells
      being approximately threefold more resistant. Pilus length had little effect upon
      survival, as the long-piliated mutants were no more resistant to killing than the
      normal-length parents. Interestingly, the receptor-binding function of type 1
      pili was most important in effecting resistance, as mutants lacking the ability
      to bind receptor were killed as effectively as nonpiliated mutants. These data
      are consistent with the notion that pili actually impede killing by macrophages
      rather than serve as passive physical barriers to uptake.

PMID- 1976117
TI  - Acquired expression of hst-1 in an autonomous subline (Chiba subline 2) derived
      from androgen-responsive mouse mammary tumor (Shionogi carcinoma 115).
AB  - Since growth of Shionogi Carcinoma 115 (SC 115) and its autonomous subline (CS 2)
      were regulated by fibroblast growth factor-like peptide, expression of int-2 and
      hst-1 was examined in these cell lines. Hybridization of genomic DNA with long
      terminal repeat of mouse mammary tumor virus (MMTV) revealed the same pattern of
      restriction fragments, showing the same integration of MMTV. Although weak
      expression of int-2 was noticed in the two cells, clear expression of hst-1 was
      seen only in CS 2 cultured with/without testosterone. It is suggested that
      autonomous growth of androgen-unresponsive CS 2 is connected with expression of
      hst-1.

PMID- 1976119
TI  - Loss of heterozygosity on chromosomes 1 and 11 in sporadic pheochromocytomas.
AB  - Molecular genetic analysis was performed with 20 oncogene probes and 32
      polymorphic DNA probes on tumor DNA samples from seven pheochromocytomas; namely,
      one multiple endocrine neoplasia type 2B, and two familial and four sporadic
      pheochromocytomas. No amplification or rearrangement of the oncogenes was
      detected in any of the tumors. However, loss of heterozygosity on chromosome 1p,
      11p or 11q was detected in these cases. In addition, a locus related to ETS1 was
      deleted in two of the sporadic tumors. These results suggest that
      pheochromocytomas may be genetically heterogeneous, and that inactivation of
      unknown genes on chromosome 1p, 11p or 11q may contribute to their development.

PMID- 1976118
TI  - c-erbB-2 and c-erbA-1 (ear-1) gene amplification and c-erbB-2 protein expression
      in Japanese breast cancers: their relationship to the histology and other disease
      parameters.
AB  - We studied c-erbB-2 and c-erbA-1 (ear-1) gene amplification, and c-erbB-2 protein
      expression in 123 primary Japanese breast cancers. c-erbB-2 amplification was
      found in 19 of the 123 tumors (15%), and c-erbA-1 was coamplified in 7 of the 19.
      The presence or absence of c-erbB-2 amplification correlated with the grade of
      cellular atypism (P = 0.008), or that of mitotic index (P = 0.002), but not with
      the histologic types. The tumor size (P = 0.04) and the lymph node status (P =
      0.06) were associated, but the patients' age, the TNM stage, or the presence or
      absence of estrogen or progesterone receptors was not associated, with c-erbB-2
      amplification. There were no differences in the histologic type, cellular
      atypism, mitotic index, and other disease parameters between tumors with c-erbB-2
      amplification only and those with coamplification of c-erbB-2 and c-erbA-1.
      Paraffin sections from all 19 tumors with c-erbB-2 amplification, and those from
      only one of 104 tumors without the amplification were positively stained with
      polyclonal anti-c-erbB-2 protein antibody. Since the correlation between the
      amplification and the protein expression was excellent, such immunohistochemical
      studies may be substituted for the time-consuming DNA studies using Southern
      blotting.

PMID- 1976120
TI  - A congenic line of the DDD mouse strain, DDD/1-Mtv-2/Mtv-2: establishment and
      mammary tumorigenesis.
AB  - A single dominant gene on chromosome 18, Mtv-2, controls both the early
      appearance of mammary tumors and expression of mouse mammary tumor virus (MMTV)
      in the milk. A congenic DDD mouse strain, DDD/1-Mtv-2/Mtv-2 (DDD-Mtv-2), was
      developed by introducing this gene from GRS/AJms (GR) into DDD/1 mice by
      repeating 12 backcrosses and subsequent inbreeding using mammary tumors as a
      marker for selection. Southern blot analysis of the liver DNA from the resulting
      congenic mice with EcoRI and MMTV-U3 prove revealed that two DNA fragments
      corresponding to Mtv-2 were specifically transferred from GR to congenic mice.
      Detection of MMTV-gp52 antigen in the mammary gland and mammary tumor development
      in DDDfDDD-Mtv-2 mice demonstrated the production of infectious mature MMTV by
      Mtv-2 in congenic mice. About 80% of breeding DDD-Mtv-2 females developed mammary
      tumors in the course of one-year follow-up. The tumor incidence was lower and the
      tumor age higher than those in GR mice, suggesting less active functioning of the
      gene on the DDD genetic background. About 70% of these tumors were
      morphologically classified as pale cell and type P carcinomas peculiar to GR
      mice. The gene seemed to control the histologic features of mammary tumors.
      Congenic mice carried an MMTV provirus in an incomplete form on Y chromosome. The
      DDD-Mtv-2-strain will provide a new model for biological and molecular researches
      into mouse mammary tumorigenesis.

PMID- 1976121
TI  - Effect of interferon-alpha in patients with chronic myelogenous leukemia in the
      accelerated phase: cytogenetic and molecular studies.
AB  - Human interferon-alpha (IFN-alpha) has been shown to be effective in the
      treatment of Philadelphia chromosome (Ph1)-positive chronic myelogenous leukemia
      (CML) in the benign stable phase. The present study indicates that IFN-alpha may
      have a suppressive effect on Ph1-positive clones not only in the early stable
      phase but also in the accelerated phase with additional chromosomal abnormalities
      in some patients. In this study, in addition to 5 benign-phase patients, 3
      patients with CML in the accelerated phase who had additional chromosomal
      abnormalities were treated with IFN-alpha. The presence of the Ph1-positive clone
      was estimated by chromosomal analysis and by Southern analysis at the DNA level
      using a 3' breakpoint cluster region (bcr) probe. Hematological remission and the
      suppression of proliferation of Ph1-positive clone to various extents were
      achieved by IFN-alpha treatment in 2 benign-phase patients and 3 patients with
      additional chromosomal abnormalities. Interestingly, in one of the latter three
      patients, Ph1-positive clones with or without additional chromosomal
      abnormalities were completely suppressed judging from chromosomal analysis and
      from the disappearance of bcr gene rearrangements.

PMID- 1976122
TI  - Generics in benzodiazepine therapy.

PMID- 1976123
TI  - Triplicate prescription forms: regulatory considerations.

PMID- 1976124
TI  - Benzodiazepine hypnotics and insomnia.
AB  - In summary, it is proposed that the more frequent or severe side effects
      associated with the newer triazolo-benzodiazepines are related to an interaction
      of several factors, including rapid elimination, high receptor-binding affinity,
      and unique chemical properties. Among benzodiazepine hypnotics, triazolam has a
      unique side effect profile for CNS adverse reactions in regard to type,
      frequency, and severity. All of the three factors mentioned contribute to this
      side effect profile: rapid elimination (the shortest half-life among
      benzodiazepine anxiolytics and hypnotics); high receptor-binding affinity (the
      highest among benzodiazepine anxiolytics and hypnotics); and unique chemical
      properties as a triazolo-benzodiazepine. Given these three factors, the drug's
      side effects can be understood as follows: Hyperexcitability states (daytime
      anxiety during drug administration and rebound insomnia following withdrawal) are
      related primarily to its rapid elimination and secondarily to the other two
      factors, whereas cognitive impairments (amnesia, confusion, and psychiatric
      symptoms) are related to the high binding affinity and unique chemical properties
      as well as to its rapid elimination. In contrast, benzodiazepines that are slowly
      eliminated and have only relatively moderate receptor-binding affinity
      (flurazepam) are unlikely to produce daytime anxiety and rebound insomnia and CNS
      adverse reactions such as cognitive impairment. The most common side effect,
      daytime sedation, is easily recognized and can be managed by dose reduction
      and/or intermittent use. This safety profile combined with the drug's high degree
      of efficacy both initially and with continued use provides a high benefit-risk
      ratio in using the drug in the adjunctive pharmacologic treatment of insomnia.
      Similarly, temazepam, which has relatively weak receptor-binding affinity
      produces very few CNS adverse reactions. Furthermore, temazepam (15 mg) is more
      efficacious than triazolam (0.25 mg). However, temazepam is not as effective as
      flurazepam, because it is slowly absorbed and therefore has limited efficacy for
      sleep induction. On the other hand, triazolam's safety profile of frequent and
      severe adverse reactions combined with the lack of efficacy for the current dose
      of 0.25 mg limits the drug's usefulness. In fact, the 0.25-mg dose has such a
      poor benefit-to-risk ratio that there is a real question as to whether the drug
      should remain on the market.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1976125
TI  - The occurrence of thyrotropin binding-inhibiting immunoglobulins and thyroid
      stimulating antibodies in patients with silent thyroiditis.
AB  - Silent (painless) thyroiditis has been recognized as a clinical entity for over a
      decade and is characterized by spontaneously resolving thyrotoxicosis. Its
      etiology is uncertain; however, a few reports have indicated the occurrence of
      TSH binding-inhibiting immunoglobulins (TBII) and thyroid-stimulating antibodies
      (TSAb) in some of the patients. The present study was undertaken to evaluate
      thyroid function and the occurrence of TBII and TSAb and thyroid autoantibodies
      (antithyroglobulin and antimicrosomal) in 53 patients with silent thyroiditis
      during the course of their disease. The patients were divided into 2 major
      groups: I) those who developed transient hypothyroidism and II) those who did
      not. All patients initially had significantly increased concentrations of serum
      T4, free T4, and free T3, suppressed TSH levels, and decreased thyroid
      radioiodine uptake. TBII and TSAb were initially positive in 8 (15.1%) and 10
      patients (18.9%), respectively. Forty patients were available for follow-up. TBII
      was positive in 6 of 24 (25.0%), and TSAb was positive in 8 of 24 (33.3%) of the
      patients who developed transient hypothyroidism during the course of their
      disease. Among the patients who did not become hypothyroid at any time, TBII was
      positive in only 2 of 16 (12.5%), and none of the patients became TSAb positive.
      The findings indicate that increased TSAb and TBII activity may be detected in
      patients with silent thyroiditis and, when present, are associated with transient
      hypothyroidism during the course of the disease.

PMID- 1976126
TI  - Immunoreactive gastrin-releasing peptide in medullary thyroid carcinoma.
AB  - We have previously shown that immunoassayable concentration of somatostatin
      (SRIH) was elevated in 70% of 34 consecutive medullary thyroid carcinoma (MTC)
      tissue samples. In the present study gastrin releasing peptide (GRP)-like
      immunoreactivity was measured in tissue extracts from these 34 MTC (25 inherited,
      7 sporadic, 2 unclassified) and in 7 normal thyroid tissue. Plasma SRIH,
      calcitonin (CT) and carcinoembryonic antigen were assayed in all patients. Normal
      thyroid tissue contained less than 61 pmol GRP per g wet weight; in contrast GRP
      concentration was elevated (62-7800 pmol/g) in 32/34 tumor extracts. The
      distribution of tissue GRP values were similar in sporadic as well as in familial
      MTC. We found no significant correlation between tumor GRP concentration and
      plasma SRIH (r = -0.05), plasma CT (r = -0.24), or plasma carcinoembryonic
      antigen levels (r = -0.21). Tumor concentrations of immunoreactive GRP and SRIH
      were positively correlated when logarithmic transformation was used (P less than
      0.01). Thus GRP, as well as SRIH, is a major product of tumoral C cells in human
      MTC when systematically evaluated in a large number of cases.

PMID- 1976127
TI  - Goitrous hypothyroidism with blocking or stimulating thyrotropin binding
      inhibitor immunoglobulins.
AB  - The significance of thyrotropin-binding inhibitor immunoglobulin (TBII) was
      evaluated in goitrous hypothyroidism associated with chronic thyroiditis (serum
      TSH greater than 10 mU/L, n = 148). TBII was measured by a RRA, and thyroid
      stimulating antibody (TSab) and thyroid-stimulation-blocking antibody (TSBab)
      were determined using porcine thyroid cells. The prevalence of patients having
      TBII was 11% or 7.4% of 148 patients, which was not significantly different from
      that of 5% or 9.6% of 52 patients with atrophic thyroiditis. Although TBII was
      shown to be TSBab in 6, TSab was found in the other 5 patients despite
      hypothyroidism. There was little correlation between severity of hypothyroidism
      and TBII or TSBab activity. One patient continued to be latently hypothyroid
      despite apparently positive TSBab. Five other patients with TSBab and 2 patients
      with TSab suffered from overt, irreversible hypothyroidism, and 2 of the patients
      with TSBab continued to be hypothyroid even after the disappearance of TSBab.
      Biopsy of the thyroid gland performed in 4 patients revealed severely damaged
      thyroid follicles with mononuclear cell infiltration with or without fibrosis.
      Three of the patients with TSab had been taking excess iodine, and recovery of
      thyroid function was observed after iodine restriction. A perchlorate discharge
      test performed in two of these patients was positive, suggesting an iodide
      organification defect. These results indicate that, although TBII is not
      infrequently found in goitrous hypothyroidism, cellular or chemical damage of the
      thyroid gland plays an important role in the pathogenesis of thyroid hypofunction
      and TSBab may only have a precipitating role.

PMID- 1976128
TI  - Therapeutic applications of drugs acting on peripheral dopamine receptors.

PMID- 1976129
TI  - Localization of gamma-glutamyl transpeptidase in human sweat glands: an
      immunohistochemical study using a monoclonal antibody.
AB  - We studied the distribution of gamma-glutamyl transpeptidase (gamma-GT) by use of
      a monoclonal antibody (MAb) against human kidney gamma-GT in human sweat glands.
      In the eccrine sweat gland, the enzyme was localized along the luminal membrane
      and small apocrine extrusions of the superficial cells of the secretory portion.
      The intercellular canaliculi between basal cells were occasionally
      immunoreactive. In the secretory portion of the apocrine gland, luminal membrane
      and apocrine extrusions of various sizes and stages at the apices of the
      secretory cells exhibited positive reactions. Immunoreaction was also seen in the
      Golgi area of the cuboidal secretory cells. No positive reaction was observed in
      the myoepithelial cells of either gland or in the excretory duct cells.

PMID- 1976130
TI  - Sensitivity of treponemal tests for detecting prior treated syphilis during human
      immunodeficiency virus infection.
AB  - To evaluate the sensitivity of treponemal tests as a marker of prior syphilis in
      individuals with human immunodeficiency virus (HIV) infection, the syphilis
      serology of 109 homosexual men with a documented history of treated syphilis was
      compared with records of prior results and confirmed on stored serum samples.
      None of the HIV-seronegative individuals lost reactivity to a treponemal test,
      whereas 7% of the seropositive asymptomatic individuals and 38% of those with
      symptomatic HIV infection had loss of reactivity. Symptomatic HIV infection was
      associated with loss of reactivity, as a T4 lymphocyte count less than 200 X
      10(6)/1, a T4-to-T8 ratio less than 0.6, a single prior episode of syphilis, and
      a low VDRL titer at the time of the last documented episode of syphilis. Although
      no conclusions can be drawn about the sensitivity of treponemal tests in patients
      with active syphilis and HIV infection, these data suggest that treponemal tests
      may not identify those previously infected with Treponema pallidum.

PMID- 1976131
TI  - Adherence characteristics to human small intestinal mucosa of Escherichia coli
      isolated from patients with diarrhea or urinary tract infections.
AB  - Formalin-fixed human ileal mucosa and formalin-fixed or untreated (native) human
      urinary bladder mucosa were used to test the adherence ability of Escherichia
      coli enterotoxigenic (ETEC) or uropathogenic (UPEC) for humans. When grown on
      colonization factor antigen (CFA) agar for 3 h at 37 degrees C, ETEC with CFA/I
      or CFA/II pili had typical peritrichous flagella and adhered strongly to human
      ileal lymphoid follicle and villus epithelium. In contrast, E. coli cells with
      CFA/I or CFA/II pili and possessing very weak or no motility displayed low levels
      of adherence to the epithelium. UPEC, which possessed type 1 pili and rarely had
      flagella, strongly adhered to human urinary bladder mucosa but not to human ileal
      epithelium. Type 1 pili-possessing E. coli isolated from human feces behaved as
      did UPEC. Moreover, M cells (microfolds) present in human ileal lymphoid follicle
      epithelium provided adherence sites for type 1 pili but not for CFA/I or CFA/II
      pili. These data demonstrate the importance of bacterial motility in efficient in
      vitro adherence to human ileal epithelia, in contrast to human urinary epithelia,
      and the adhesin specificity of bacterial adherence to M cell microfolds.

PMID- 1976132
TI  - Studies of human leprosy lesions in situ using suction-induced blisters. 2. Cell
      changes and soluble interleukin 2 receptor (Tac peptide) in reversal reactions.
AB  - To examine the pathogenesis of type 1 (reversal) reactions in leprosy, we studied
      cellular and soluble immunologic components of skin lesions in 10 patients with
      reactions, 24 active patients without reactions, and 33 control patients whose
      leprosy had been treated and cured. Cells and Tac-peptide levels were obtained
      from fluid aspirated from blisters induced by suction directly over
      representative skin lesions. During reversal reactions: a) the lesions contained
      an increased number and percentage of CD4+ (T-helper) cells; b) Tac-peptide
      levels were elevated in half of the lesions; c) the increases in Tac peptide and
      CD4+ cells were directly correlated; and d) systemic administration of
      corticosteroids appeared to cause a reduction in the intralesional CD4+ cell
      population. These findings were localized to the skin, and do not represent
      simple filtration of these components from the peripheral blood. We conclude that
      spontaneous lymphocyte activation in situ, primarily of CD4+ cells, is an
      important feature of reversal reactions, and may be an intermittent or cyclic
      phenomenon during the reaction. Findings in active patients without reactions are
      consistent with the hypothesis that differing states of immunologic equilibrium
      have been established in different portions of the leprosy spectrum. In reversal
      reactions we may, therefore, be examining immunologic processes set in motion
      when a pre-existing equilibrium has been upset by spontaneous, natural events.
      The mechanism of such spontaneous changes in immunity in leprosy is of
      considerable interest, not only to understand the reaction, but also to examine
      the underlying determinants of delayed-type hypersensitivity and cell-mediated
      immunity in leprosy and the potential for artificially manipulating these
      responses, as proposed with vaccines or immunotherapy.

PMID- 1976133
TI  - Short-loop inhibition of thyrotrophin-releasing hormone-induced growth hormone
      secretion in fowl.
AB  - The i.c.v. administration of 0.1 or 10 micrograms ovine (o)GH to 12- to 16-week
      old hypothyroid chickens of a sex-linked dwarf (SLD) strain suppressed the basal
      plasma GH concentrations, measured 24 h afterwards. The GH response of the oGH
      injected SLDs to TRH was suppressed, in a dose-related way, in comparison with
      that induced by TRH in birds given control injections (10 micrograms) of bovine
      serum albumin (BSA). Basal circulating concentrations of GH in euthyroid K strain
      birds of the same age were even lower than in the SLDs following injection of 10
      micrograms oGH, and were not further reduced by oGH administration. The GH
      response to TRH in the K strain birds injected i.c.v. with 0.1 or 10 micrograms
      oGH was, nevertheless, suppressed in comparison with the BSA-injected K strain
      controls. The i.c.v. administration of oGH also suppressed circulating
      concentrations of LH and the LH response to TRH in the K strain birds. Twenty
      four hours after i.c.v. administration of oGH (10 micrograms), the somatostatin
      (SRIF) content in the medial basal hypothalamus of 8-week-old euthyroid cockerels
      was greater than that in BSA (10 micrograms)-injected controls. At the same time,
      the binding of [3H]3-methyl-histidine2-TRH to the pituitary caudal and cephalic
      lobes of GH-injected birds was less than that in the controls. These results
      suggest that GH regulation in avian species is partly mediated by an inhibitory
      short-loop mechanism (mediated by hypothalamic SRIF and a down-regulation of
      pituitary TRH-binding sites) that suppresses basal and secretagogue-induced GH
      release.

PMID- 1976134
TI  - Thyrotrophin increases the alpha 1b-adrenergic receptors in rat thyroid gland in
      vivo.
AB  - Using chlorethylclonidine (CEC), an alpha 1b-adrenergic receptor-selective
      antagonist, we characterized alpha 1-adrenoceptor subtypes in rat thyroid gland,
      and investigated the effect of methimazole (MMI)-induced high TSH levels on alpha
      1 receptor subtypes and noradrenaline-induced iodide organification. The density
      of thyroid alpha 1-adrenergic receptors was increased about sixfold in rats
      treated with MMI for 3 weeks compared with controls. Pretreatment of thyroid
      membrane preparations with CEC (10 mumol/l) caused an 83% decrease in specific 2
      [beta-(hydroxy-3-[125I]iodophenyl) ethylaminomethyl]tetralone binding sites in
      MMI-treated rats, but only a 43% decrease in control rats. The density of CEC
      insensitive alpha 1 receptors (alpha 1a) was similar in MMI-treated and control
      rats, so MMI was shown to increase CEC-sensitive alpha 1 receptors (alpha 1b).
      Noradrenaline-stimulated iodide organification was threefold greater in MMI
      treated rats than in control rats when values were expressed as a per cent
      increase over basal levels. Pretreatment of thyroid lobes with 10 mumol CEC/l for
      30 min caused a 66% decrease in maximal noradrenaline-induced iodide
      organification in MMI-treated rats, but a significantly lower decrease (49%) in
      control rats. These results suggest that the rat thyroid gland contains both
      alpha 1a and alpha 1b receptors, both of which mediate noradrenaline-induced
      iodide organification, and also that TSH enhances noradrenaline-induced iodide
      organification by increasing alpha 1b receptor density.

PMID- 1976135
TI  - In utero transplantation of hematopoietic stem cells in sheep: the role of T
      cells in engraftment and graft-versus-host disease.
AB  - Transplantation of hematopoietic stem cells (HSC) from adult sheep into fetal
      lambs results in hematopoietic chimerism and graft-versus-host disease (GVHD). To
      evaluate the role of T cells in HSC engraftment and GVHD we depleted adult marrow
      HSC of T cells and observed the incidence of chimerism and GVHD in the fetal
      recipients. Using a naturally occurring polymorphism of the beta-globin locus to
      detect engraftment, bone marrow obtained from homozygous type A hemoglobin adult
      sheep were transplanted (2 x 10(9) cells/kg fetal weight) into 90 days' gestation
      fetal lambs homozygous for type B hemoglobin. Donor HSC were T-cell depleted by
      treatment with antisera (raised in rabbits against sheep thymocytes) in the
      presence of complement. T-cell depletion resulted in significant decrease in
      hematopoietic colony formation by donor HSC in vitro (305 +/- 49 v 134 +/- 21
      colonies/10(5) cells) that normalized by the addition of autologous T cells (433
      +/- 32 colonies/10(5) cells). Marrow depleted of T cells exhibited reduced
      engraftment in the recipient fetuses. When T cells were added back to donor HSC
      (depleted of T cells) at near-normal concentrations, engraftment improved but the
      lambs also developed GVHD. The addition of T cells to donor HSC (depleted of T
      cells) at concentrations below that present in unprocessed bone marrow resulted
      in significant engraftment but not GVHD. T cells play an important role in both
      the engraftment of adult HSC in fetal recipients and the development of GVHD in
      chimeric newborns. The elimination of T cells prevents GVHD but markedly reduces
      engraftment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1976137
TI  - [A review of larvivorous fish].
AB  - Recently, because of concern about the effects of insecticide on the environment,
      increased attention is being given to the use of biological agents for
      controlling the vectors of human disease. Biological control may encompass the
      use of predators, pathogens, parasites, pheromones, insect growth regulators, and
      other factors. Of these agents only fish and bacteria have so far been used
      operationally in mosquito control. Since 1988 fish have been employed for
      controlling Aedes larvae in water containers in Liuchiu, Pingtung. A review of
      larvivorous fish (mainly Gambusia affinis) and the present status of the use of
      fish in mosquito control in Mainland China are thus made for ready reference for
      the workers in mosquito control in Taiwan.

PMID- 1976136
TI  - HT1080/DR4: a P-glycoprotein-negative human fibrosarcoma cell line exhibiting
      resistance to topoisomerase II-reactive drugs despite the presence of a drug
      sensitive topoisomerase II.
AB  - HT1080/DR4 (DR4) is a doxorubicin-resistant human fibrosarcoma line that exhibits
      150-fold cross-resistance to etoposide but does not overexpress P-glycoprotein
      (one mechanism of multiple drug resistance). We examined another possible
      mechanism that could explain resistance to both doxorubicin and etoposide: a
      quantitative or qualitative alteration in topoisomerase II, the putative nuclear
      target of these agents. The amount of immunoreactive topoisomerase II present in
      whole-cell lysates and nuclear extracts was three- to 10-fold lower in DR4 than
      in HT1080 cells. However, the topoisomerase II in nuclear extracts from both
      lines was sensitive to the effects of amsacrine (AMSA) and etoposide. Following
      treatment with AMSA, etoposide, and 5-iminodaunorubicin, topoisomerase II
      mediated DNA cleavage in DR4 cells and nuclei was reduced compared with cleavage
      in HT1080 parent cells and nuclei. The difference between the HT1080 and DR4
      lines in AMSA- and 5-iminodaunorubicin-induced cleavage was similar in cells and
      nuclei and could be due to the lower amount of DR4 topoisomerase II. By contrast,
      the difference between the HT1080 and DR4 lines in etoposide-induced DNA cleavage
      was much greater in cells than in nuclei. This finding suggested that cytosolic
      factors, removed from isolated nuclei, could influence the susceptibility of
      intact cells to the cytotoxic and DNA-cleaving actions of etoposide. The specific
      activities of several antioxidant enzymes, components of the cell's defense
      against free-radical damage that may be produced by doxorubicin or etoposide,
      were significantly different in HT1080 and DR4 cytosolic extracts. These
      differences may constitute an additional mechanism of resistance. Regardless, the
      magnitude of the resistance of DR4 to doxorubicin and etoposide cannot be
      explained solely on the basis of a topoisomerase II-related mechanism.

PMID- 1976138
TI  - [The pathogens of Taiwan mosquitoes--Coelomomyces species].
AB  - A brief mention was made of the history of world studies on the Coelomomyces
      fungi, the life cycle of the fungi, their importance as biological agents for
      mosquito control, and the known ecological information concerning the Taiwan
      mosquitoes parasitized by the fungi. Special accounts were made of the results of
      experiments infecting four mosquito species, Aedes aegypti, Ae. albopictus, Ae.
      triseriatus and Tripteroides aranoides with Coelomomyces stegomyiae var.
      chapmani, using the copepod, Phyllognathopus viguieri as an alternate host. The
      dead 4th instar larvae of Ae. albopictus containing sporangia were put together
      with healthy copepods for 10 days, then healthy 2nd instar mosquito larvae were
      added for a 1-day exposure. Then the larvae were transferred to clean water and
      subsequent examinations for signs of infection were made at 3-day intervals for a
      period of 21 days. The experiments demonstrated an infection rate of 59.7% and
      90% respectively for Ae. albopictus and Ae. aegypti in the first trial, 18.5% and
      23.3% in the 2nd trial, and none in the 3rd trial. The low infection rate in the
      2nd trial and no infection in the 3rd trial were thought to be due to the
      extensive contamination of test water with algae. Therefore, in the 4th trial the
      rearing water was renewed with dechlorinated tap water and new copepods
      instroduced. The infection rate again rose to 41.1% and 56% respectively for the
      two species. Experiments with Ae. triseriatus and Tp. aranoides failed to produce
      signs of infection. Experimental infection of susceptible Ae. albopictus larvae
      with the sporangia stored at 8 degrees C showed that storage for one month
      produced an infection rate of 38.2%. However, storage for two months or longer
      produced no infection in the larvae of the same mosquito species.

PMID- 1976139
TI  - Allelic association of human dopamine D2 receptor gene in alcoholism.

PMID- 1976140
TI  - [Drug-induced myopathy--clofibrate, succinylcholine, heroin, L-dopa, steroid
      hormone].

PMID- 1976141
TI  - Immunoglobulin heavy chain switch region gene polymorphisms in
      glomerulonephritis.
AB  - Much evidence suggests that primary IgA nephropathy (IgAN) and idiopathic
      membranous nephropathy (MN) are immune complex mediated diseases. Moreover,
      genetic factors may play an important role in their pathogenesis. Recently,
      restriction fragment length polymorphisms (RFLPs) of the immunoglobulin heavy
      chain genes have been described which appear to associate with
      glomerulonephritis. We have studied RFLPs of the switch region of the IgM (S mu)
      and IgA1 (S alpha 1) heavy chain in MN and IgAN. DNA obtained from British
      Caucasoids with IgAN (N = 75), MN (N = 43), and normal controls (N = 73), was
      digested with the restriction enzyme Sac1, and studied using Southern blot
      techniques and hybridization with a 32P labelled DNA probe homologous to S mu.
      This probe detects RFLPs at the S mu and S alpha 1 loci. The genotypic and
      allelic frequencies of the S mu and S alpha 1 alleles in IgAN and MN was similar
      to normal controls. Caucasoid subjects with IgAN from Northern and Southern
      Europe (Finland and Italy, respectively) were also studied to determine whether
      an ethnic variation in genetic susceptibility to IgAN exists. The frequency of
      the S mu and S alpha 1 alleles was similar between the patient groups and their
      respective local healthy controls. These results do not support the recent
      findings of an association with RFLPs of the S mu and S alpha 1 loci in IgAN and
      MN, and suggest that the immunoglobulin heavy chain switch region genes are not
      important in conferring disease susceptibility to IgAN or MN.

PMID- 1976142
TI  - The risks and benefits of an Rx-to-OTC switch. The case of over-the-counter H2
      blockers.
AB  - In recent years, many new over-the-counter (OTC) medications have resulted from
      the granting of OTC status by the U.S. Food and Drug Administration to drug
      entities that previously were available only by prescription (Rx). While the
      benefits to consumers of Rx-to-OTC switches may be substantial, they also involve
      some degree of risk, as usage typically expands and physician supervision
      diminishes. This study explores the potential utility of techniques of decision
      analysis in evaluating the balance of these benefits and risks. Histamine H2
      receptor antagonists (H2-blockers), which are currently available only by
      prescription, are presented as a case study and were examined to determine how
      OTC availability of these agents would alter the patterns, effectiveness, and
      risks of self-treatment for acid-peptic disorders. Currently, about 5.7 million
      persons experience an episode of dyspepsia during any given quarter, of whom 3.5
      million self-medicate with antacids. Study results indicate that OTC availability
      of H2-blockers would: 1) increase the proportion of persons with dyspepsia who
      self-medicate from 61.8% currently to 64.1%; 2) increase the proportion of
      persons who experience complete relief of their symptoms while self-medicating
      from 37.9% currently to 43.2%; 3) result in 14 additional cases of serious
      hematologic disorders and an additional 22,000 instances of minor side effects
      per quarter, but cause the overall rate of side effects among persons who self
      medicate to decline; 4) cause an additional 300 persons per quarter with gastric
      cancer to self-medicate before seeking professional care, but cause no change in
      the median time between onset of symptoms and the decision to seek such care; and
      5) decrease by 277,000 the number of persons per quarter who seek professional
      care for dyspepsia. On balance, results suggest that OTC H2-blockers may be a
      relatively safe and effective means of self-care for acid-peptic disorders, and
      may substantially reduce the number of patient encounters with the medical care
      system for minor gastrointestinal complaints. This study also illustrates the
      potential utility of the techniques of decision analysis to the formulation of
      drug regulatory policy.

PMID- 1976143
TI  - Evidence implicating at least two genes on chromosome 17p in breast
      carcinogenesis.
AB  - The DNA of paired tumour and blood leucocyte samples from a large series of
      breast cancer patients was analysed to map regions of loss of heterozygosity on
      chromosome 17. The high frequency of loss of heterozygosity on 17p was confirmed,
      and a third of informative tumours had also lost an allele at the long arm locus
      THH59. On the short arm two distinct regions of loss of heterozygosity were
      identified, in bands p13-3 and p13-1. The latter probably involves the structural
      gene p53, which has been implicated as an oncogene or as a tumour suppressor in
      various human cancers. 17p 13-3, however, showed a significantly higher frequency
      of loss of heterozygosity, and there was no correlation between allele losses at
      the two sites. Nevertheless, loss of heterozygosity at 17p 13-3 is associated
      with overexpression of p53 mRNA, suggesting the existence of a gene some 20
      megabases telomeric of p53 that regulates its expression. Lesions of this
      regulatory gene seem to be involved in the majority of breast cancers.

PMID- 1976144
TI  - Antimicrobial actions of calcium binding leucocyte L1 protein, calprotectin.
AB  - The calcium binding L1 protein was found to inhibit growth of blood culture
      isolates of Candida spp and cerebrospinal fluid isolates of Cryptococcus
      neoformans. Minimum inhibitory concentrations (MIC) were 4-128 mg/l, and
      concentrations 2-4 times the MIC were fungicidal. Blood culture isolates of
      Escherichia coli, Klebsiella spp, Staphylococcus aureus, and Staphylococcus
      epidermidis had MIC values of 64-256 mg/l. Antibacterial activity was strongly
      influenced by the nature of the culture medium. In view of the biological
      activity of L1, the name calprotectin is proposed to describe this antimicrobial
      protein with calcium binding properties.

PMID- 1976145
TI  - Jejunal efflux in short bowel syndrome.
AB  - 24 h oral intake and intestinal output were studied in 15 patients with a short
      residual length of jejunum and no colon. 8 patients showed a net secretory, and 7
      a net absorptive response to food. In secretors, daily intestinal output exceeded
      oral intake (mean 2.3 kg wet weight, and 233 mmol sodium). Long-term parenteral
      fluid and electrolyte replacements were needed only in those with a secretory
      response. Jejunal length inversely correlated with net intestinal output of
      fluid, sodium, potassium, and with percentage energy absorption. A secretory
      response was observed if jejunal length was less than 100 cm and was reduced by
      gastric antisecretory drugs and octreotide.

PMID- 1976146
TI  - Limited role of fetal blood sampling in prediction of outcome in intrauterine
      growth retardation.
AB  - Fetal acid-base status was evaluated on 66 blood samples taken for rapid
      karyotyping from 58 growth-retarded fetuses. Before blood sampling, doppler blood
      flow studies of the umbilical artery showed end-diastolic frequencies to be
      absent in 32 fetuses (group 1) and present in 26 (group 2). Fetuses with
      chromosomal (n = 4) or structural (n = 8) abnormalities were excluded from
      subsequent analysis. Gestational age at blood sampling (27.8 [95% CI 26.5-29.1]
      vs 32.2 [30.4-34.1] weeks) and time from sampling to delivery (median 2 (range 0
      35] vs 14 [0-77] days) were significantly lower in group 1 than group 2. There
      were no perinatal deaths in group 2 whereas mortality in group 1 was 65.4%. There
      were significant differences between the groups at blood sampling in pH, pO2,
      pCO2, base equivalents, and nucleated-red-cell count, but within group 1 these
      measurements were similar in surviving fetuses and those who died perinatally.
      Since acid-base determination does not predict perinatal outcome in growth
      retarded fetuses, fetal blood sampling has a limited role in monitoring fetal
      wellbeing.

PMID- 1976148
TI  - Fibroblast growth factors: time to take note.

PMID- 1976147
TI  - Comparison of carbon-dioxide-enriched, oxygen-enriched, and normal air in
      treatment of acute mountain sickness.
AB  - Twenty mountaineers with acute mountain sickness (AMS) at an altitude of 4559 m
      were randomly allocated to treatment with oxygen-enriched (33% oxygen), carbon
      dioxide-enriched (3% carbon dioxide), or normal compressed air. Treatment with
      oxygen significantly improved the arterial partial pressure of oxygen (PaO2),
      relieved symptoms of AMS, and reduced cerebral blood flow as estimated by
      transcranial doppler ultrasound examination of the median cerebral artery. The
      only significant effect of carbon dioxide was increased ventilation resulting in
      a slight rise in PaO2. Thus, in contrast to previous uncontrolled trials, this
      study does not support the usefulness of carbon dioxide treatment in AMS.

PMID- 1976149
TI  - Loading the lods.

PMID- 1976150
TI  - Gastroenterologists in Sydney--histology and helicobacter.

PMID- 1976151
TI  - Tainted treacle.

PMID- 1976152
TI  - Driving and Parkinson's disease.

PMID- 1976153
TI  - European Community collaborative study of outcome of pregnancy between 22 and 28
      weeks' gestation. Working Group on the Very Low Birthweight Infant.
AB  - International comparison of perinatal mortality rates is subject to various
      problems in methods of reporting. The main difficulties are differences in the
      definition of livebirth and the variation in policies on the elective delivery of
      very preterm fetuses at risk of intrauterine death. This study, based on
      geographically defined populations within the European Community, set out to
      compare survival rates in very low birthweight infants (below 1500 g). The first
      phase of the study in seven populations showed pronounced differences in survival
      and in the proportion of liveborn infants who weighed less than 1000 g. A further
      phase studied the outcome of all pregnancies from 22 to 28 weeks' gestation in
      four populations. There was no significant difference between the four
      populations in crude survival rates per 1000 livebirths among infants born at 22
      to 28 weeks' gestation, but more babies were born alive at the earlier gestations
      in the United Kingdom. Survival rates were higher in Scotland and England when
      gestational age at birth was controlled for. Future comparisons of the outcome of
      perinatal care for extremely immature infants would be more meaningful if data on
      the outcome of all pregnancies ending after 22 weeks' gestation were routinely
      collected through the registration system.

PMID- 1976154
TI  - Mianserin and agranulocytosis in New Zealand.
AB  - The frequency with which agranulocytosis was associated with mianserin in New
      Zealand was calculated, by two methods, from spontaneous reports to the Intensive
      Medicines Monitoring Programme (IMMP)--one gave a frequency of 1 in 1354 (95% CI
      1 in 3145 to 1 in 685) and the other gave a rate of 1 in 1743 (95% CI 1 in 2895
      to 1 in 1116). There were 3 deaths. Age and dose seemed to be related to
      occurrence of agranulocytosis. The frequency of the complication seemed to be
      higher than that reported for other countries, perhaps because higher doses were
      prescribed in New Zealand but also perhaps because of a selection bias in surveys
      elsewhere. The occurrence of agranulocytosis with mianserin in New Zealand is
      higher than that of white-cell dyscrasias reported with use of chloramphenicol,
      phenylbutazone, and oxyphenbutazone, and although the case-fatality rate of
      agranulocytosis is lower with mianserin than with the other drugs, the overall
      mortality rate may be higher.

PMID- 1976155
TI  - Epidemiology of foodborne illness: North America.

PMID- 1976156
TI  - Epidemiology of foodborne illness: UK.

PMID- 1976157
TI  - America through the looking glass: 1, Medical student years.

PMID- 1976158
TI  - Using oneself as one's only experimental subject.

PMID- 1976159
TI  - Confidential documents in HIV/haemophilia litigation.

PMID- 1976160
TI  - Lack of relation between IgE in neonatal period and later atopy.

PMID- 1976161
TI  - Oilseed rape not a potent antigen.

PMID- 1976162
TI  - Latex as aeroallergen.

PMID- 1976163
TI  - Deformability of erythrocytes stored between -20 and -25 degrees C.

PMID- 1976164
TI  - The secret of sex.

PMID- 1976165
TI  - ACE inhibitors and peripheral vascular disease.

PMID- 1976166
TI  - Ketoconazole in treatment of visceral leishmaniasis.

PMID- 1976167
TI  - Malaria chemoprophylaxis: why mefloquine?

PMID- 1976168
TI  - Morbidity due to intestinal helminthiasis.

PMID- 1976169
TI  - Improved results with PCR for chronic myeloid leukaemia.

PMID- 1976170
TI  - Iodine-induced hypothyroidism in infants treated with continuous cyclic
      peritoneal dialysis.

PMID- 1976171
TI  - Polycythaemia and HIV infection.

PMID- 1976172
TI  - Carbenoxolone in HIV-related oropharyngeal ulceration.

PMID- 1976173
TI  - Intrathecal zidovudine for AIDS dementia.

PMID- 1976174
TI  - Apolipoprotein(a) and ischaemic heart disease.

PMID- 1976175
TI  - Pharmacokinetic data for ropinirole.

PMID- 1976176
TI  - Benzene in petrol: a continuing hazard.

PMID- 1976177
TI  - Pseudo deep-vein thrombosis following desferrioxamine infusion: a previously
      unreported adverse reaction?

PMID- 1976178
TI  - Health inequalities and migrant workers in Switzerland.

PMID- 1976179
TI  - International trends in cancer mortality.

PMID- 1976180
TI  - Causes of excess mortality in The Netherlands and England and Wales 1989/90.

PMID- 1976181
TI  - Insight.

PMID- 1976182
TI  - Dihydropyrimidinuria.

PMID- 1976183
TI  - Bone density screening for osteoporosis.

PMID- 1976184
TI  - Antenatal screening for toxoplasmosis.

PMID- 1976185
TI  - Caesarean section for fetal distress.

PMID- 1976186
TI  - Fetal haemorrhage after fetal scalp blood sampling.

PMID- 1976187
TI  - Fetal neural graft survival.

PMID- 1976188
TI  - Anticardiolipin co-inhibitor in normal human serum.

PMID- 1976189
TI  - Urticaria and hepatitis C.

PMID- 1976190
TI  - Anti-HCV testing in autoimmune hepatitis and primary biliary cirrhosis.

PMID- 1976191
TI  - Interferon-induced enhancement of 2',5'-oligoadenylate synthetase in mid-gut
      carcinoid tumours.

PMID- 1976192
TI  - IgA mesangial nephritis, IgA antigliadin antibodies, and coeliac disease.

PMID- 1976193
TI  - Hyposensitivity of basal cell naevus syndrome dermal fibroblasts to ultraviolet
      A.

PMID- 1976194
TI  - Co-expression of N-ras p21 and C-erbB-2 (neu) oncogene products by common ALL
      antigen-positive aggressive diffuse lymphoma.

PMID- 1976195
TI  - Darwin's illness.

PMID- 1976196
TI  - Atrial natriuretic factor activates membrane-bound guanylate cyclase of chief
      cells.
AB  - The present study examined the effect of atrial natriuretic factor (ANF) on cGMP
      generation by dispersed chief cells from guinea pig stomach. ANF caused a rapid
      dose-dependent increase in cGMP, a 7-fold increase in cGMP caused by 1 microM
      ANF, with or without 3-isobutyl-1-methylxanthine present. Methylene blue reduced
      cGMP in response to nitroprusside but not ANF. Guanylate cyclase activity of a
      chief cell membrane fraction doubled in response to ANF, but was not affected by
      nitroprusside. ANF had no effect on guanylate cyclase activity of the soluble
      fraction of lysed chief cells. Dose-response curves for whole cell cGMP
      production and membrane guanylate cyclase activity in response to ANF were
      closely related. These data indicate that ANF increases chief cell cGMP
      production by activating particulate guanylate cyclase, providing functional
      evidence that chief cells possess surface membrane receptors for ANF.

PMID- 1976197
TI  - Hemorphins, cytochrophins, and human beta-casomorphins bind to antiopiate (TYR
      MIE-1) as well as opiate binding sites in rat brain.
AB  - Novel peptides with opiate activity, derived from endogenous sources (human and
      bovine casomorphins from milk, hemorphins from hemoglobin, and cytochrophins from
      mitochondrial cytochrome b), were tested for their ability to inhibit binding of
      the brain peptide Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) to its high affinity sites in
      rat brain. The order of potency in inhibiting binding of 125I-Tyr-MIF-1 was:
      hemorphin and bovine casomorphins greater than Tyr-MIF-1 greater than
      cytochrophins greater than human casomorphins. Naloxone and DAMGO were
      ineffective at inhibiting Tyr-MIF-1 binding. The results provide evidence that,
      in addition to their ability to bind to mu opiate receptors, these novel
      endogenous peptides with opiate activity and a peptide (Tyr-MIF-1) with
      antiopiate properties also bind to a non-opiate site labeled by Tyr-MIF-1. These
      sites could be involved in a balance between opiate and antiopiate peptides.

PMID- 1976198
TI  - Differential effect of membrane depolarization on levels of tyrosine hydroxylase
      and dopamine beta-hydroxylase mRNAs in PC12 pheochromocytoma cells.
AB  - Membrane depolarization has been widely used to elucidate the response of the
      nervous system to prolonged neuronal activity or stress. We studied the effect of
      treating PC12 cells with membrane depolarizing stimuli, 50 mM KCl, or 150 microM
      veratridine, and the subsequent changes in the mRNA levels of the catecholamine
      biosynthetic enzymes, tyrosine hydroxylase (TH) and dopamine beta-hydroxylase
      (DBH). TH mRNA levels were found to increase 2- to 5-fold after continuous
      treatment for 1-12 h with 50 mM KCl. Depolarization with 150 microM veratridine
      had a similar effect on TH mRNA. In contrast, DBH mRNA levels were unchanged by
      either KCl or veratridine treatment. The role of calcium in the increase of TH
      mRNA levels elicited by depolarization was examined. The increase in TH mRNA was
      inhibited by the chelation of calcium with 3 mM EGTA. However, in contrast to
      their effect on phosphorylation of TH elicited by acute depolarization, the
      calcium channel blockers, nitrendipine and verapamil, and the calmodulin
      antagonists, W7 and trifluoperazine, did not prevent the increase in TH mRNA
      levels subsequent to several hours exposure to depolarizing stimuli. The calcium
      ionophore, A23187, alone was unable to induce TH mRNA levels. Thus, the increase
      in TH mRNA elicited by depolarization is mediated differently than the acute
      phosphorylation of the enzyme.

PMID- 1976200
TI  - Somatostatin: basic and clinical aspects. Proceedings of the International
      Symposium on Somatostatin. Montreal, Canada, August 6-9, 1989.

PMID- 1976199
TI  - Analysis of tyrosine hydroxylase and insulin transcripts in human neuroendocrine
      tissues.
AB  - We have previously shown that the mRNA for human tyrosine hydroxylase (TH) exists
      in one of 4 forms as a result of alternative splicing of intron 1. In order to
      determine the tissue-specific expression of the multiple human transcripts we
      have utilized specifically primed polymerase chain reactions (PCR) in combination
      with reverse-transcribed RNA. Using PCR analysis we determined that many human
      neuronal tissues express all 4 forms of human TH (hTH-1-4); however, hTH-3 and -4
      are generally expressed at less than 1% of the other two. Of all tissues
      examined, only pancreatic beta-islet cells expressed a single form of human TH
      mRNA (hTH-2). The mRNA for rat TH is present in only one form, the equivalent of
      hTH-1. Since we have shown that the human genes for TH and insulin are only 2.7
      kb apart and several groups have reported insulin-like expression in neuronal
      tissues, we looked for insulin transcription in the same central and peripheral
      nervous system samples. Insulin mRNA was not present within the limits of
      detection.

PMID- 1976201
TI  - Somatostatin inhibition of hormone release: effects on cytosolic Ca++ and
      interference with distal secretory events.
AB  - In normal pituitary cells somatostatin (SRIF) blocks the spontaneous oscillations
      in [Ca++]i by inhibiting the generation of action potentials. This is sufficient
      to explain the inhibitory effect on basal, but not entirely that on stimulated
      pituitary hormone secretion. In insulin secreting cells, which, in contrast to
      pituitary cells, only fire action potentials on stimulus-evoked depolarization,
      SRIF hyperpolarization and lowering of [Ca++]i is only transient. The marked
      inhibition of insulin secretion is suggested to be due to a coordinated action of
      SRIF on membrane potential and [Ca++]i as well as a direct interference with late
      secretory events.

PMID- 1976202
TI  - Somatostatin regulation by cytokines.
AB  - Inflammatory states are associated with nervous and neuroendocrine responses,
      which appear to be mediated through the actions of cytokines. Since endotoxin
      treatment in the rat is associated with declines in thyrotropin (TSH) secretion
      and growth hormone (GH) secretion, changes that may be explained by stimulation
      of hypothalamic somatostatin (SRIF), the effects of cytokines on SRIF were
      examined. In an in vitro model system consisting of fetal rat diencephalic cells
      interleukin-1 (IL-1), tumor necrosis factor (TNF) and interleukin-6 (IL-6) were
      found to stimulate the synthesis and release of SRIF. This effect developed
      slowly over 24 hours and was dose- and time-dependent. Acute release of SRIF over
      periods up to 1 hour was not found. The mechanism of cytokine stimulation of SRIF
      is not known. Since the depletion of glial cells in the cultures inhibits the
      effect, mediators that depend on the presence glia may be involved. The ability
      of cytokines to stimulate brain SRIF is likely to prove relevant to our
      understanding in many areas, including brain development, brain responses to
      injury, and neuroendocrine changes in chronic illness.

PMID- 1976203
TI  - Somatostatin and epilepsy.
AB  - Hippocampal neurons containing somatostatin have been shown to be vulnerable in
      some experimental models of epilepsy. In this report, we describe our recent
      findings about the seizure-related changes in somatostatin in brain tissue and
      cerebrospinal fluid (CSF) in experimental and human epilepsy. These data
      strengthen the view that the somatostatinergic system is affected in epilepsy.

PMID- 1976204
TI  - Somatostatin in neurodegenerative illnesses.
AB  - Somatostatin may play a role in several neurodegenerative diseases. Somatostatin
      concentrations are depleted in cerebral cortex in both Alzheimer's disease and in
      the dementia that accompanies Parkinson's disease. Somatostatin neurons in both
      illnesses are markedly dystrophic and may be reduced in number. In Huntington's
      disease, somatostatin concentrations are increased in the basal ganglia, as is
      the density of somatostatin neurons. The precise role of somatostatin changes in
      the pathophysiology of these illnesses requires further study.

PMID- 1976205
TI  - Mechanisms for muscarinic inhibition of somatostatin release from canine fundic D
      cells.
AB  - We undertook the present studies to explore the mechanisms by which carbachol
      inhibits the release of somatostatin-like immunoreactivity (SLI) from D cells. D
      cells were isolated from canine fundic mucosa by collagenase/EDTA dispersion
      followed by counterflow elutriation. Carbachol inhibited the release of SLI
      induced by forskolin, dibutyryl 3':5' cyclic adenosine monophosphate (cAMP),
      pentagastrin (PG), and 12-0-tetradecanoyl-phorbol-13-acetate in a fashion that
      could be prevented by pertussis toxin (PT) pretreatment of the D cells. Pertussis
      toxin also prevented the carbachol-induced inhibition of forskolin-stimulated
      cAMP generation and PG-stimulated [Ca2+]i mobilization. These data indicate that
      pertussis toxin sensitive inhibitory guanine nucleotide binding proteins mediate
      many of carbachol's inhibitory actions on D cells.

PMID- 1976206
TI  - Regulation of gastric somatostatin gene expression.
AB  - Regulation of somatostatin gene expression was studied in the rat gastric antrum.
      Antral total RNA was isolated from animals during starvation and after refeeding,
      or under gastric neutralization by fundectomy or by omeprazole treatment.
      Northern blot analysis using cRNA probe synthesized from a cloned rat
      somatostatin cDNA demonstrated a single hybridizing band, approximately 850
      nucleotides in length, which is present in the antrum. Quantitative slot blot
      analyses were able to detect significant changes of somatostatin mRNA levels in
      total RNA as low as 5 micrograms. Somatostatin mRNA levels increased
      significantly after 12 hours of fasting (144% of control) and remained elevated
      throughout the 4-day fasting period. Upon refeeding with solid food and
      phenylalanine, antral somatostatin returned to the prefasted level in 2 hours.
      Refeeding with olive oil or saline depressed somatostatin mRNA significantly
      within 30 to 60 minutes but did not attain the prefasted state. Fundectomy and
      omeprazole resulted in maximal inhibition of antral somatostatin mRNA levels by
      77% and 78%, respectively. The present in vivo results indicate that somatostatin
      gene expression in the stomach is regulated by luminal factors that include pH
      and specific nutrients. Future studies based on this phenomenon can expand
      knowledge of the interactions between gastric endocrine cells and the gastric
      environment.

PMID- 1976207
TI  - Mechanisms regulating somatostatin release and somatostatin-induced acetylcholine
      release from the myenteric plexus.
AB  - The present studies were performed to characterize the molecular form(s) of
      somatostatin present in the myenteric plexus and to examine some aspects of the
      regulatory mechanisms underlying somatostatin release and somatostatin-induced
      release of acetylcholine from this tissue. We observed the following: (1)
      Somatostatin-like immunoreactivity (SLI) is present in the myenteric plexus of
      the guinea pig ileum with somatostatin-14 being the predominant molecular form.
      (2) Somatostatin-like immunoreactivity is released from isolated myenteric
      ganglia after stimulation with veratridine or the ganglionic agonist
      dimethylphenylpiperazinium (DMPP). (3) Calcium entry via the N-type channel
      appears to play a dominant role in DMPP-induced release of SLI. (4) Somatostatin
      regulates its own release via a pertussis toxin-sensitive mechanism. (5) Under
      basal conditions somatostatin-14 stimulates release of acetylcholine in a
      concentration-dependent manner. (6) Calcium entry via L-type channels is
      associated with the release of acetylcholine evoked by somatostatin-14.

PMID- 1976208
TI  - Cellular mechanisms of somatostatin action in the gut.
AB  - We have used isolated canine parietal cells to examine the receptor and
      postreceptor events mediating the inhibitory effects of somatostatin on acid
      secretion. Somatostatin-14 (S14) and somatostatin-28 (S28) dose dependently
      inhibited parietal cells stimulated by secretagogues that activate both the
      adenylate cyclase/cyclic adenosine monophosphate and the inositol
      phospholipid/protein kinase C cascades. The inhibitory action was mediated via a
      specific cell surface receptor that consists of a single subunit protein
      (molecular weight 99,000 d). This receptor recognized S14 and S28 equally well.
      Somatostatin inhibited parietal cell activity via mechanisms that are both
      dependent on and independent of a pertussis toxin-sensitive inhibitory guanine
      nucleotide binding protein.

PMID- 1976209
TI  - Gastric somatostatin: a paracrine regulator of acid secretion.
AB  - The presence of acid in the lumen of the gastric fundus induces release of
      somatostatin close to the parietal cells; this acts to attenuate acid secretion
      in response to secretagogues, such as histamine and gastrin. The release of
      somatostatin within the stomach is further regulated by the activity of
      cholinergic neurons that inhibit somatostatin release and thus augment acid
      secretion (disinhibition), and noncholinergic (bombesin) neurons that stimulate
      somatostatin release and thus attenuate acid secretion. The influence of these
      neurons and the participation of somatostatin as a paracrine regulator of acid
      secretion has been probed and validated by the use of selective antagonists
      (atropine and a bombesin antagonist), somatostatin antiserum and pertussis toxin.
      Similar mechanisms exist in the distal antral segment of the stomach for the
      paracrine regulation of gastrin release by somatostatin.

PMID- 1976210
TI  - Antitumor effects of somatostatin mediated by the stimulation of tyrosine
      phosphatase.

PMID- 1976211
TI  - Efforts directed at understanding cell-specific somatostatin gene expression.

PMID- 1976212
TI  - Treatment of nonendocrine gastrointestinal disorders with octreotide acetate.
AB  - Somatostatin and its longer-acting analog, octreotide acetate, can be used
      effectively for the treatment of nonendocrine gastrointestinal disorders.
      Octreotide has been shown to decrease pancreatic fistula output by suppressing
      exocrine pancreatic function. We believe that octreotide acetate may be useful to
      prophylaxis against the development of pancreatic fistulas following pancreatic
      resection and may reduce the enzymatic and volume output of established
      pancreatic fistulas. We also have shown that administration of octreotide acetate
      2 hours before a high carbohydrate test meal reduces gut peptide levels, which
      increase following meal ingestion in patients with the dumping syndrome.
      Reduction of circulating peptides in these patients may slow gut motility and
      improve glucose regulation, thus, providing relief of postvagotomy dumping
      symptoms.

PMID- 1976214
TI  - Processing of prosomatostatin.
AB  - Several peptides are generated from prosomatostatin (proSS) in addition to
      somatostatin-14 (SS-14) and somatostatin-28 (SS-28). These are SS-28(1-12),
      proSS(1-76) and, as shown more recently, proSS(1-63) and antrin. Important
      variations in the proportion of these molecular forms are seen among different
      tissues and among different species. Processing of the precursor in the human
      brain yields minimal quantities of SS-28(1-12) and high levels of proSS(1-76),
      namely in cortical areas and in the bed nucleus of the stria terminalis. This is
      in contrast with findings in rat brain, where SS-28(1-12) is a predominant
      molecular form. Antrin, which corresponds to proSS(1-10), reaches its highest
      concentration in the antral portion of the stomach (117 +/- 13 pmol/g wet
      weight), where it is found in secretory granules of delta cells. We observed an
      inverse relationship between levels of antrin and proSS(1-63) after
      chromatography of various tissue extracts. This suggests a precursor-product
      relationship between these two peptides.

PMID- 1976213
TI  - Somatostatin gene regulation: an overview.
AB  - The somatostatinergic system has proven to be one of the best models of
      neuropeptide biology. Originally characterized as a hypothalamic regulator of
      growth hormone secretion, somatostatin also regulates the secretion of several
      other pituitary, pancreatic, and gastrointestinal (GI) hormones including
      thyrotropin-stimulating hormone, insulin, glucagon, and gastrin. Disorders in
      somatostatin metabolism have been proposed to contribute to the pathogenesis of
      Alzheimer's disease, epilepsy, GI motility disorders, and diabetes. On a more
      basic level, studies of somatostatin action have integrated divergent concepts of
      intracellular signal transduction. Advances in the understanding of somatostatin
      biosynthesis have had an impact on areas outside the field of endocrinology by
      providing new concepts of eukaryotic gene regulation. This report focuses on the
      transcriptional regulation of somatostatin gene expression. Two aspects of
      somatostatin gene transcription will be considered--regulated expression by
      second messengers and tissue-specific basal expression.

PMID- 1976215
TI  - Processing and intracellular sorting of anglerfish and rat preprosomatostatins in
      mammalian endocrine cells.
AB  - Rat preprosomatostatin (rPPSS) is processed to two distinct end products in a
      tissue-specific manner. The analogous end products in anglerfish are derived from
      separate precursors, anglerfish preprosomatostatins-1 and -2 (a(1)PPSS and
      a(II)PPSS). This report reviews experiments demonstrating that in mammalian
      cells, the cell of expression, not precursor structure, determines the processing
      fate of the preprosomatostatins. A fusion precursor of a(II)PPSS and rPPSS was
      expressed in mammalian cell lines to determine that the amino-terminal 78
      residues of rPPSS contain a sorting signal that directs the precursor into a
      regulated secretory pathway wherein proteolytic processing occurs. Preliminary
      studies of rPPSS pro-region mutations are presented that attempt to further
      localize this sorting signal.

PMID- 1976216
TI  - Purification of prosomatostatin-converting enzymes.
AB  - The enzymes responsible for performing cleavage of propeptides at basic amino
      acids have proven difficult to characterize. Using the processing of anglerfish
      islet prosomatostatin (PSS) as a model system, we are pursuing the
      characterization of both a single basic amino acid-specific and a dibasic amino
      acid-specific converting enzyme. We describe here the model system and protein
      isolation methods that have allowed significant progress toward complete
      characterization of the somatostatin-generating propeptide converting enzymes
      (PCEs).

PMID- 1976217
TI  - Interplay of somatostatin and growth hormone-releasing hormone in genesis of
      episodic growth hormone secretion.

PMID- 1976218
TI  - Physiological role of somatostatin on growth hormone regulation in humans.
AB  - Growth hormone (GH) secretion in man is pulsatile and this pattern is regulated
      by both GH-releasing hormone (GHRH) and somatostatin. A large body of
      experimental evidence in both man and animals supports the model that bursts of
      GH secretion are mediated by a reduction of tonic hypothalamic somatostatin
      secretion. Our studies have been performed in normal subjects with frequent blood
      sampling for GH measurements (from 20-minute to 30-second intervals); the data
      have been analyzed by computer algorithms to objectively determine pulse
      characteristics and, in some studies, to estimate both pituitary secretion and
      clearance rates using deconvolution analysis. The studies include profiles of GH
      secretion in normal men and women in fed and fasted states; analysis of GH
      secretion during sleep; and administration of GHRH during different stages of
      sleep and after sleep deprivation. The variable GH response to exogenous GHRH and
      the attenuated response after 6 hours of GHRH infusion to GHRH, while not to
      hypoglycemia, as well as the pulsatile profile of GH secretion in response to
      continuous GHRH infusions (24 hours to 14 days), all support the thesis that it
      is hypothalamic somatostatin that determines the timing of bursts of GH
      secretion. This is further confirmed by the profile of GH secretion in a patient
      with ectopic GHRH secretion. Recently, we have initiated studies with the novel
      synthetic GH releasing hexapeptide, HisDTrpAlaTrpDPheLysNH2 (GHRP). Our studies
      show that it acts synergistically with GHRH. Several lines of evidence suggest
      that GHRP stimulates GH secretion independently of GHRH receptors and acts at
      both the hypothalamic and pituitary levels. It may act to functionally antagonize
      somatostatin.

PMID- 1976219
TI  - Somatostatin secretion and action in the regulation of growth hormone secretion.
AB  - The inhibition of growth hormone (GH) secretion by the hypothalamic peptide,
      somatostatin, is mediated by two critical factors: the concentration of the
      peptide in hypothalamic portal plasma and the number of somatostatin (SRIF)
      receptors on the somatotroph. The secretory patterns of SRIF and GH-releasing
      hormone (GRH) in portal blood of unanesthetized sheep is pulsatile and a close
      relationship of GRH pulses to those of GH secretion was documented, while those
      of SRIF appear to have more of a modulatory role on the responses to GRH.
      Peripheral infusion of SRIF at a rate to provide concentrations comparable to
      those in the portal system leads to a desensitization of SRIF effects on the
      somatotroph, likely mediated by down-regulation of SRIF receptors. These effects
      are believed to modulate the GH responses to GRH secretion in the generation of
      pulsatile GH secretion.

PMID- 1976220
TI  - Regulation of somatostatin and growth hormone-releasing hormone gene expression
      in the rat brain.
AB  - We have studied the regulation of somatostatin (SS) and growth hormone-releasing
      hormone (GHRH) gene expression in the brain of the laboratory rat. We report that
      hypophysectomy in the adult male reduces SS mRNA in cells of the periventricular
      nucleus (PeN), while GH reverses this effect. We demonstrate that cellular levels
      of SS mRNA in the PeN are higher in male compared to female animals. We report
      that castration reduces cellular levels of GHRH mRNA and SS mRNA in the arcuate
      nucleus and PeN, respectively, and that testosterone reverses this effect through
      an androgen receptor-dependent mechanism. Finally, we present a theoretical model
      to explain the generation of the ultradian rhythm in GH secretion, which
      implicates the reciprocal interaction between GH feedback and the transcriptional
      regulation of the SS and GHRH genes and the kinetics of these relationships.

PMID- 1976221
TI  - Role of somatostatin and its analogues in the pathogenesis and treatment of
      diabetes mellitus.
AB  - Somatostatin secreted by pancreatic D cells is a potent inhibitor of insulin,
      glucagon and growth hormone secretion, as well as other cells. The role of
      abnormal pancreatic D-cell function in diabetes mellitus is unclear. However,
      development of long-acting selective somatostatin analogs might prove useful in
      the treatment of diabetes.

PMID- 1976222
TI  - Islet somatostatin--microvascular, paracrine, and pulsatile regulation.
AB  - The possible role of the D cell in the regulation of islet hormone secretion has
      been controversial for many years. It is known that the D cells
      characteristically reside in the islet mantle interspaced among A cells. We have
      shown by the anterograde and retrograde infusion of antibody directed against
      insulin, glucagon, or somatostatin into the isolated rat and dog pancreas that
      blood flow within the islet is from the B-cell core outward to the mantle.
      Despite the apparent randomness of the A and D cell in the mantle, our results
      indicate a further suborder of cellular perfusion in the mantle with the A cells
      perfused before the D cells. The D cells are last in line in terms of secretion.
      Thus the D cell is vascularly neutral and cannot directly effect A- or B-cell
      secretion through the intra-islet vasculature. Our results demonstrate that the B
      to A to D cellular order of perfusion is responsible for the regulation of islet
      hormone secretion, ie, insulin regulates the secretion of glucagon and glucagon
      (and probably insulin) regulate the secretion of somatostatin. Although each
      hormone is secreted as pulses, there does not appear to be a consistent phase
      relationship between insulin, glucagon, or somatostatin. The B to A to D cellular
      order of perfusion is responsible for net and integrated hormone secretion, but
      may not be the motive force of pulsatile secretion. Our studies have not
      documented a role for intra-islet mantle somatostatin. These results strongly
      suggest that the D cell is not a paracrine regulator of islet hormone secretion,
      but may be important in the regulation of exocrine function.

PMID- 1976223
TI  - Mechanism of action of somatostatin: an overview of receptor function and studies
      of the molecular characterization and purification of somatostatin receptor
      proteins.
AB  - To determine whether somatostatin receptor subtypes arise from molecular
      heterogeneity of the receptor protein, we have cross-linked the putative receptor
      in normal rat tissues and in AtT-20 and GH3 cells, both chemically with SS-14, SS
      28 and Tyr3 SMS ligands, as well as by photoaffinity labeling with an azido
      derivative of Tyr3 SMS (EE 581). Three prominent somatostatin receptor proteins
      of 58-kDa, 32-kDa, and 27-kDa size have been identified. These proteins exhibit a
      tissue-specific distribution, ligand selectivity, and relative preference for SS
      14 and SS-28 binding, and thus qualify as somatostatin receptor subtypes. Using
      EE 581 as a photoaffinity probe, the 58-kDa and 32-kDa proteins have been
      purified to homogeneity from brain and AtT-20 cells by successive SDS-PAGE. The
      58-kDa form has been trypsinized and amino acid sequence data obtained from four
      tryptic fragments. With the help of synthetic oligonucleotides derived from these
      sequences, work is currently in progress to clone the 58-kDa protein to elucidate
      its complete sequence, its expression, and its functional relationship to the
      somatostatin receptor and its pharmacological subtypes.

PMID- 1976224
TI  - Molecular characterization of a purified human gastric somatostatin receptor.

PMID- 1976226
TI  - Somatostatin action in pituitary cells involves two independent transduction
      mechanism.

PMID- 1976225
TI  - Electrophysiological effects of somatostatin-14 and somatostatin-28 on mammalian
      central nervous system neurons.
AB  - Somatostatin (SOM) exists in at least two active forms in the central nervous
      system (CNS): SOM-14 and SOM-28. These peptides have multiple actions on neurons
      in the CNS and these actions appear to be mediated by different receptors. Thus,
      SOM-14 can enhance voltage-dependent K currents, whereas SOM-28 inhibits these
      same currents, sometimes even in the same neurons. These effects are not mediated
      via cAMP, but do seem mediated by GTP-binding proteins. On the other hand, both
      forms of SOM inhibit a voltage-dependent Ca current, again via a GTP-binding
      protein. SOM can also interact with the GABA(A) receptor to modulate responses to
      this inhibitory transmitter. The physiological effects of SOM in an integrated
      circuit within the CNS will depend on the form of SOM released, the kinds and
      numbers of receptors present on the postsynaptic neurons, and the presence of
      other neurotransmitters.

PMID- 1976227
TI  - p-[125I]iodoclonidine, a novel radiolabeled agonist for studying central alpha 2
      adrenergic receptors.
AB  - Unlabeled p-iodoclonidine was efficacious in attenuating forskolin-stimulated
      cAMP accumulation in SK-N-SH neuroblastoma cells. Maximal attenuation was 76 +/-
      3%, with an EC50 of 347 +/- 60 nM. Comparable values of epinephrine were 72 +/-
      3% and 122 +/- 22 nM. Responses to both agonists were abolished by 10 microM
      phentolamine. Therefore, p-iodoclonidine is an agonist in a cell culture model
      system of the neuronal alpha 2-adrenergic receptor. p-[125I]Iodoclonidine binding
      to membranes were measured using various regions of the rat brain. The agonist
      labeled a single population of sites present on cerebral cortical membranes,
      which was saturable (Bmax = 230 fmol/mg of protein) and possessed high affinity
      for the ligand (Kd = 0.6 nM). Binding was largely specific (93% at 0.6 nM). A
      variety of alpha 2-adrenergic agonists and antagonists were shown to compete for
      the binding of the radioligand. The binding of p-[125I]iodoclonidine was much
      less sensitive to agents that interact with alpha 1-adrenergic, serotonergic, and
      dopaminergic receptors. Approximately 65% of the binding was sensitive to guanine
      nucleotides. Association kinetics using 0.4 nM radioligand were biphasic (37%
      associate rapidly, with kobs = 0.96 min-1, with the remainder binding more
      slowly, with kobs = 0.031 min-1) and reached a plateau by 90 min at 25 degrees.
      Dissociation kinetics were also biphasic, with 30% of the binding dissociating
      rapidly (k1 = 0.32 min-1) and the remainder dissociating 50-fold more slowly (k2
      = 0.006 min-1). Agonist binding is, therefore, uniquely complex and probably
      reflects the conformational changes that accompany receptor activation.

PMID- 1976228
TI  - Lack of cross-desensitization of somatostatin-14 and somatostatin-28 receptors
      coupled to potassium channels in rat neocortical neurons.
AB  - The effects of somatostatin-14 (SOM-14) and somatostatin-28 (SOM-28) on the
      delayed rectifier K+ current (IK) in rat neocortical neurons in culture were
      measured by using whole-cell patch clamp techniques. SOM-14 stimulated IK in a
      reversible manner. Continuous application of SOM-14 to the neocortical neurons
      led to a gradual desensitization of the SOM-14 response. Many cells became
      completely densensitized to SOM-14. SOM-28 also modulated IK in neocortical
      cells. However, SOM-28 reduced IK. This response was also reversible. Continuous
      application of SOM-28 to neocortical neurons led to a desensitization of the SOM
      28 inhibition of IK. Many of the neurons that responded to SOM-28 became
      completely refractory to the peptide following prolonged SOM-28 pretreatment.
      While most neocortical neurons responded either to SOM-14 or to SOM-28, a
      population of neurons responded to both peptides. Chronic application of SOM-14
      to these neurons completely desensitized the SOM-14 stimulation of IK but did not
      affect SOM-28 inhibition of this potassium current. Similarly, complete
      desensitization of SOM-28 responses in these cells was not associated with a
      modification of SOM-14 stimulation of IK. The lack of cross-desensitization
      between SOM-14 and SOM-28 induced responses suggests that these peptides act
      through different receptors to regulate IK.

PMID- 1976229
TI  - Different amino acids at position 57 of the HLA-DQ beta chain associated with
      susceptibility and resistance to IgA deficiency.
AB  - The human leukocyte antigens (HLA) are implicated in the genetic susceptibility
      to a large number of diseases. Some of the diseases associated with HLA class II
      are related to specific amino acids or epitopes of the domain of the HLA class II
      molecule that is distal to the membrane. In man, selective immunoglobulin A
      deficiency is the most common immunodeficiency, frequently resulting in recurrent
      sino-pulmonary infections and gastro-intestinal disorders. Associations have been
      described with HLA class I, and to a lesser extent with different class II
      alleles, which might indicate that they share some common feature. Here we study
      95 IgA-D patients and find positive associations with three DR-DQ haplotypes and
      a strong negative association with a fourth haplotype. Comparison of the
      sequences of the polymorphic amino-terminal domain of the DQ beta chain showed
      that the three 'susceptibility' haplotypes all had a neutral alanine or valine at
      position 57. The 'protective' allele had the negatively charged aspartic acid at
      this position (Asp57). Codon 57 of the HLA-DQ beta chain has been implicated in
      the susceptibility to insulin-dependent diabetes mellitus. Our data suggest that
      the same amino acid position could possibly also influence susceptibility and
      resistance to selective immunoglobulin A deficiency.

PMID- 1976230
TI  - Formation of micro-liver by intestine epithelial HGF in primary culture.

PMID- 1976231
TI  - Alpha 2-adrenoceptor-mediated autoinhibition of sympathetic transmitter release
      in guinea-pig vas deferens studied by intracellular and focal extracellular
      recording of junction potentials and currents.
AB  - Excitatory junction potentials (e.j.ps; intracellular electrodes) and excitatory
      junction currents (e.j.cs; extracellular electrodes) elicited by stimulation (20
      pulses at 1 Hz every minute) of the hypogastric nerve trunk were recorded from
      guinea-pig isolated vas deferens. Intracellular recording. At a variety of
      stimulation intensities, bath-applied yohimbine (0.1-1 mumol/l) did not change
      the first one to three e.j.ps in a train but increased the amplitude of
      subsequent e.j.ps. The effect of yohimbine was abolished in tissues from
      reserpine-pretreated guinea pigs. Bath-applied desipramine (0.1 mumol/l)
      diminished the amplitude of all but the first one to three e.j.ps in a train.-
      Extracellular recording. Yohimbine (0.1-1 mumol/l), when applied locally through
      the recording suction electrode, increased the number of e.j.cs per given number
      of stimuli, i.e., enhanced the probability of occurrence of e.j.cs. When
      desipramine (0.1 mumol/l) was present both in the bath and in the recording
      electrode, the probability of the occurrence of e.j.cs was decreased. In the
      presence of desipramine, yohimbine (0.1-1 mumol/l) increased the number of e.j.cs
      even more markedly. Neither the nerve terminal impulse nor the number of
      spontaneous e.j.cs was changed by yohimbine. A mixture of tetraethylammonium (2
      mmol/l) and 4-aminopyridine (0.2 mmol/l), when applied locally, both increased
      the number of e.j.cs and changed markedly the shape of the nerve terminal
      impulse.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1976232
TI  - Veratridine and other depolarizing agents counteract the inhibitory effect of
      Mg2+ ions on N-methyl-D-aspartate (NMDA)-induced noradrenaline release in vitro.
AB  - Rat brain cortex slices preincubated with 3H-noradrenaline were superfused with
      Krebs-Henseleit solution with or without Mg2+. In the absence of Mg2+ ions, NMDA
      evoked 3H-noradrenaline overflow above basal efflux; this effect was
      concentration-dependently inhibited by Mg2+ (IC50: 19 mumol/l). Despite the
      presence of 1.2 mmol/l Mg2+, which is known to block cation influx through the
      ion channel coupled to the NMDA receptor, NMDA evoked 3H-noradrenaline release if
      the membrane was permanently kept depolarized by 20 or 25 mmol/l K+, 1 mumol/l
      veratridine or 200 mumol/1 3,4-diaminopyridine; the stimulant effect of NMDA was
      counteracted by 2-amino-5-phosphonovaleric acid (2-APV), a competitive antagonist
      at the NMDA receptor and by (+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohept
      5,10-imine hydrogen maleate (MK 801), an antagonist acting at the cation channel
      associated with the NMDA receptor. In contrast, no stimulatory effect of NMDA in
      the presence of 1.2 mmol/l Mg2+ was observed when the membrane of the nerve
      terminals was intermittently depolarized by electrical impulses of 2 ms duration
      at a frequency of 1-3 Hz. It is concluded that continuous depolarization of the
      nerve membrane counteracts the blocking effect of Mg2+ on cation influx through
      the NMDA receptor-associated ion channel. Under this condition, noradrenaline
      release can be stimulated by NMDA receptor activation even in the presence of
      physiological Mg2+ concentrations.

PMID- 1976233
TI  - The competitive NMDA receptor antagonists CGP 37849 and CGP 39551 are potent,
      orally-active anticonvulsants in rodents.
AB  - Anticonvulsant properties of CGP 37849 and CGP 39551, two novel phosphono-amino
      acids which are competitive NMDA receptor antagonists, were examined in rodents.
      At optimal pretreatment times CGP 37849 suppressed electroshock-induced seizures
      in mice and rats with ED50s ranging from 8 to 22 mg/kg after oral administration,
      and 0.4 to 2.4 mg/kg after i.v. and i.p. injection. Relative to CGP 37849, CGP
      39551 was more potent after p.o. (ED50 3.7-8.1 mg/kg), and less potent after i.v.
      or i.p. treatment (ED50 2.7-8.7 mg/kg). Following oral treatment, the duration of
      action of CGP 37849 was about 8 h, while CGP 39551 still showed good activity
      after 24 h (ED50 8.7 mg/kg, mouse; 21 mg/kg, rat). Both compounds were
      anticonvulsant at doses below those at which overt behavioural side effects were
      apparent. CGP 39551 delayed the development of kindling in rats at doses of 10
      mg/kg p.o. and above, and showed weak anticonvulsant activity against
      pentylenetetrazol-evoked seizures. CGP 37849 and CGP 39551 are the first
      competitive NMDA antagonists to show oral anti-convulsant properties in a
      therapeutically-useful dose-range, and hence are interesting candidates for novel
      antiepileptic therapy in man.

PMID- 1976235
TI  - A study of glutamine synthetase in normal human brain and intracranial tumours.
AB  - Glutamine synthetase (GS) activity was measured in selected areas of three normal
      brains and in 262 biopsies from patients with suspected intracranial tumours. In
      general, levels were higher in grey matter than in white matter and the highest
      activities of all were found in the hypothalamus which is consistent with its
      high glutamatergic activity. In the biopsy material, GS activity was greatest in
      gliotic brain, in keeping with the predominantly astrocytic localization of the
      enzyme. High levels were also found in astrocytomas and oligodendrogliomas but
      there was considerable variation between tumours, suggesting a random loss of GS
      expression during neoplastic transformation or heterogeneity in their cellular
      origin. The immunocytochemical demonstration of GS in neoplastic oligodendrocytes
      and in meningioma cells argues against absolute cell-type specificity for this
      enzyme.

PMID- 1976234
TI  - Different types of opioid receptors mediating analgesia induced by morphine,
      DAMGO, DPDPE, DADLE and beta-endorphin in mice.
AB  - The effects of intracerebroventricular (i.c.v.) administration of D-Phe-Cys-Tyr-D
      Try-Orn-Thr-Pen-Thr-NH2 (CTOP), a selective mu-opioid receptor antagonist,
      (Allyl)2-Tyr-Aib-Aib-Phe-Leu-OH (ICI 174864) and (N,N-Bisallyl-Tyr-Gly-Gly-psi
      (CH2S)-Phe-Leu-OH (ICI 154129), selective delta-opioid receptor antagonists on
      blocking analgesia induced by beta-endorphin, morphine, D-Ala2-NMePhe4-Gly-ol
      enkephalin (DAMGO), D-Ala2-D-Leu5-enkephalin (DADLE) and D-Pen2-enkephalin
      (DPDPE) administered i.c.v. were studied in male ICR mice. The analgesia was
      assessed by the tail-flick and paw-licking (hot-plate) tests. The potencies of
      opioid agonists injected i.c.v. for producing analgesia were DAMGO greater than
      DADLE greater than beta-endorphin greater than morphine greater than DPDPE.
      Intracerebroventricular administration of CTOP (0.05 micrograms) selectively
      antagonized inhibition of the tail-flick and paw-licking response induced by
      morphine, DAMGO or DADLE but not beta-endorphin or DPDPE. ICI 174864 (5
      micrograms) and ICI 154129 (5 micrograms) injected i.c.v. selectively antagonized
      analgesia induced by DPDPE or DADLE but not beta-endorphin, morphine or DAMGO
      injected i.c.v. These results indicate that analgesia induced by morphine and
      DAMGO is mediated by the stimulation of mu-opioid receptors while analgesia
      induced by DPDPE is mediated by the stimulation of delta-opioid receptors. DADLE
      induced analgesia is mediated by the stimulation of both mu- and delta-opioid
      receptors. Analgesia induced by beta-endorphin is mediated by neither mu- nor
      delta-opioid receptors.

PMID- 1976236
TI  - Are putative dopamine-accumulating cell bodies in the hypothalamic
      periventricular organ a primitive brain character of non-mammalian vertebrates?
AB  - The brains of the chicken, Gallus domesticus, and two amphibians, the anuran Rana
      ridibunda and the urodele Pleurodeles waltlii, were investigated by means of
      immunohistochemical techniques with antibodies against dopamine (DA) and tyrosine
      hydroxylase (TH). As could be expected on the basis of the catecholamine
      biosynthetic pathway, cell bodies that are immunopositive for the DA antiserum
      also stain with the TH antibodies. However, a remarkable discrepancy is observed
      in the hypothalamic periventricular organ where liquor contacting cells exhibit
      DA- but no TH-immunoreactivity. Since similar results have been obtained in
      reptiles but not in mammals, it may be concluded that these putative DA
      accumulating cells are a primitive brain character of non-mammalian vertebrates.

PMID- 1976238
TI  - Atopic keratoconjunctivitis.
AB  - The clinical presentation and severe complications of atopic
      keratoconjunctivitis, a potentially blinding disorder, were characterized in a 9
      year retrospective study of 45 patients seen at a large referral center. Twenty
      six patients had subepithelial fibrosis, 13 with symblepharon and/or fornix fore
      shortening. Thirty-four patients had severe keratopathy, which included
      neovascularization in 17 patients. Persistent epithelial defect was another major
      complication, occurring in 21 eyes and causing severe loss of vision. These
      patients required interdisciplinary therapeutic strategies; systemic
      antihistamine therapy and strict environmental controls were the keys to success
      in most cases.

PMID- 1976237
TI  - Sleep-promoting action of excitatory amino acid antagonists: a different role for
      thalamic NMDA and non-NMDA receptors.
AB  - Changes in the sleep-waking cycle of freely moving cats were studied during
      application of excitatory amino acid antagonists in the ventro-posterolateral
      thalamic nuclei by microdialysis. DL-2-Amino-5-phosphono-pentanoic acid (APV), a
      selective N-methyl-D-aspartate (NMDA) receptor antagonist, produced an increase
      in the deep stages of slow wave sleep and in paradoxical sleep and a decrease in
      the light stages of slow wave sleep (SWS1), while 6-cyano-7-nitroquinoxaline-2,3
      dione (CNQX), at a concentration selective for the non-NMDA receptors, produced a
      marked increase in SWS1. These results indicate a strong sleep-promoting action
      of excitatory amino acid antagonists and suggest that thalamic NMDA and non-NMDA
      receptors may play different roles in sleep regulation. Thus, changes in the
      sleep-waking cycle should be carefully evaluated when assessing the potential
      clinical use of excitatory amino acid antagonists.

PMID- 1976239
TI  - Disruption of phase during PCR amplification and cloning of heterozygous target
      sequences.
AB  - PCR amplification of genomic DNA or cDNA has become a standard tool for
      identification of mutations underlying genetic disease. There are inherent
      limitations in the application of this method in compound heterozygotes. One
      problem which is encountered is the disruption of phase (linkage) between
      heterozygous polymorphisms represented on heterologous alleles. A test system was
      used to demonstrate and quantitate the disruption of phase between two
      polymorphic restriction sites. Phase is disrupted in approximately 1% of the PCR
      amplified material, possibly due to incomplete chain elongations and subsequent
      priming on the heterologous allele. Phase is disrupted in approximately 1/4 of
      cloned PCR fragments, possibly due to excision repair of heteroduplexes during
      cloning. The implications of these disruptions for the use of PCR in identifying
      mutations are discussed.

PMID- 1976241
TI  - Nucleotide sequence of rat hsp60 (chaperonin, GroEL homolog) cDNA.

PMID- 1976240
TI  - Somatotroph- and lactotroph-specific interactions with the homeobox protein
      binding sites in the rat growth hormone gene promoter.
AB  - Nuclear extracts prepared from growth hormone-secreting (GC) and prolactin
      secreting (235-1) rat anterior pituitary cell lines were compared for their
      ability to bind to the DNA sequences conferring tissue-specificity to the
      expression of the rat growth hormone (rGH) gene promoter. Cell-specific
      differences in the interaction of Pit-1, a tissue-specific member of the POU
      domain transcription factor family, with the pGHF1 binding site were detected by
      methylation interference experiments; otherwise the Pit-1 proteins present in GC
      cell and 235-1 cell extracts were similar. Two other protein/DNA complexes, GHF5
      and GHF7, were detected by gel mobility shift assays and the binding of both
      complexes to the rGH promoter depended upon DNA sequences contained within the
      two binding sites for Pit-1. In contrast to Pit-1 which can bind to either of the
      two sites independently, a single Pit-1 binding site was insufficient for GHF5
      and GHF7 binding; i.e. both Pit-1 binding sites within the rGH promoter were
      required. Whereas GHF5 was present in nuclear extracts of GC cells and a variety
      of cells not producing growth hormone, GHF7 binding activity was detected only in
      the GC cell line (and not in the 235-1 cell line). GHF7 binding activity was
      therefore more closely correlated with growth hormone gene transcription than was
      Pit-1. rGH promoters containing mutations which inhibited GHF5, GHF7 and Pit-1
      binding were expressed less efficiently than the wild type promoter after
      transfection into GC cells. One promoter mutation to which the GHF7 complex but
      not the Pit-1 factor can bind was also transcription deficient demonstrating that
      Pit-1 binding, independent of GHF7 binding, was nevertheless important to the
      expression of the rat growth hormone promoter.

PMID- 1976242
TI  - A 50 bp polymorphic insertion in the factor IX gene is readily detected by
      amplification and is in equilibrium with other polymorphic sites.

PMID- 1976243
TI  - XmnI polymorphism in the human TPA gene.

PMID- 1976244
TI  - Human parathyroid hormone-like peptide gene: HindIII and TaqI RFLPs.

PMID- 1976245
TI  - RFLP for intron E of factor XI gene.

PMID- 1976246
TI  - An anonymous DNA probe M7 (D7S422) on chromosome 7 associated with two RFLP's.

PMID- 1976247
TI  - Dopamine-induced relaxation of the guinea-pig isolated jejunum is not mediated
      through dopamine receptors.
AB  - The possible involvement of specific dopamine receptors in the relaxing effect of
      dopamine in the guinea-pig isolated jejunum has been investigated. The relaxing
      effect of dopamine does not show the tachyphylaxis phenomenon and it is present
      in preparations from guinea-pigs pretreated with reserpine. These results
      indicate that dopamine has a direct action. Comparison of the effect of dopamine
      with those of other dopamine receptor agonists, i.e. apomorphine, bromocriptine
      and the DA1 selective fenoldopam, were made to calculate potency ratios. Since
      apomorphine, bromocriptine and fenoldopam were shown to relax the guinea-pig
      jejunum, partly behaving as indirectly acting agents, comparisons were made on
      reserpine-pretreated guinea-pigs. It has been found that apomorphine is 2.5
      times, fenoldopam 3 times and bromocriptine 20 times more active than dopamine in
      relaxing the guinea-pig jejunum. The order of potency is different from that
      found in other dopamine receptors containing tissues. The effects of the dopamine
      receptor blockers, haloperidol and cis-alpha-flupenthixol and the DA1 selective
      blocker SCH 23390 on the relaxing effect of dopamine were also studied. The
      relaxing effect of dopamine was not reduced by haloperidol, cis-alpha
      flupenthixol and SCH 23390. It is concluded that specific postjunctional dopamine
      receptors are not involved in the relaxing action of dopamine. Since dopamine is
      known to interact with alpha- and beta-adrenoceptors in a variety of tissues, the
      effects of the alpha-adrenoceptor blocker phentolamine and the beta-adrenoceptor
      blocker propranolol on the relaxing effect of dopamine were also studied.
      Noradrenaline has been used to check the responsiveness of the tissue.
      Phentolamine did not block the responses to dopamine and propranolol was able
      only to partially reduce responses to dopamine, at concentrations higher than
      those at which it antagonized noradrenaline. Mechanisms other than dopamine,
      alpha- or beta-receptor activation should be involved in the relaxing effect of
      dopamine in the guinea-pig jejunum.

PMID- 1976248
TI  - The relationship between gamma-glutamyl transpeptidase and Hg levels in Se/Hg
      antagonism in mouse liver and kidney.
AB  - The gamma-glutamyl transpeptidase (gamma-GT) activity and Hg concentrations were
      studied in Se/Hg antagonism in mouse liver and kidney after treatment with methyl
      mercury (MM) (MM group) and MM + sodium selenite (SE) (SM group). In acute
      treatment (dietary doses: MM = 250 p.p.m.; SE = 90 p.p.m.; length of treatment 11
      days), hepatic gamma-GT activity increased in both protected and unprotected
      animals with respect to controls and reached a peak after 3 days with respect to
      controls, its value being relatively greater in the MM group. On the contrary,
      renal gamma-GT decreased with time with respect to controls and was higher in the
      SM group at 3 and 7 days. Liver and kidney accumulation of Hg increased and
      decreased respectively with time, and was higher in SM groups in most cases. In
      chronic treatment (dietary doses: MM = 12.5 p.p.m.; SE = 9 p.p.m.; length of
      treatment 12 months) hepatic gamma-GT activity in the MM group was higher than in
      the SM group at 1.5 and 7 months, whereas the renal activity was lower at 7
      months and unchanged at 1.5 and 12 months. In comparison with the acute
      treatment, the trend of Hg accumulation was similar in liver and different in
      kidney; Hg concentrations of the SM group were always greater than those of the
      MM group. Glutathione (GSH) in liver and non-protein SH groups (NPSH) in kidney
      were also measured in acutely treated animals. On the first day GSH was about 50%
      of the control value in both the MM and SM groups; it subsequently remained
      constant in the MM group, but increased to a peak at 7 days, without reaching the
      control value, in the SM group. Unlike the liver, renal NPSH increased in both
      groups on the first day, and then decreased with time without reaching the
      control value, SM group values always exceeding those of MM group. The modulation
      of gamma-GT activity in liver and kidney caused by SE suggests that the enzyme
      plays a role in Hg accumulation.

PMID- 1976249
TI  - Homeodomain of yeast repressor alpha 2 contains a nuclear localization signal.
AB  - The yeast repressor alpha 2 is shown, by analysis of deletion-bearing alpha 2
      beta-galactosidase hybrid proteins, to have two structurally distinct nuclear
      localization signals. The cellular location of hybrid proteins was determined by
      indirect immunofluorescence and optical sectioning of whole fixed yeast cells.
      The two nuclear localization signals are far apart in the alpha 2 primary
      structure and do not have any sequence homology. One signal is, as reported
      previously, within the aminoterminal 13 amino acids of alpha 2. Deletion of only
      this aminoterminal signal has no evident effect on nuclear localization. The
      second signal is in a central portion of alpha 2, within the alpha 2 homeodomain.
      Since this signal is within the amino terminus of the alpha 2 homeodomain, the
      homeodomain mediates nuclear localization in addition to, and independently of,
      DNA binding. Deletion of only this second signal results in inefficient
      localization and accumulation of mutant protein at discrete sites on the nuclear
      envelope assumed to be nuclear pores. We propose that the two signals in alpha 2
      are functionally distinct and act at different steps in a localization pathway.

PMID- 1976250
TI  - Dynorphin A and cAMP-dependent protein kinase independently regulate neuronal
      calcium currents.
AB  - The kappa-selective opioid peptide dynorphin A (DYN) inhibits neuronal adenylate
      cyclase activity and reduces neuronal voltage-dependent calcium currents. It is
      not yet known, however, whether the regulation of calcium channel activity is
      dependent on or independent of the adenylate cyclase/cAMP system. We used the
      whole-cell variation of the patch clamp technique to show that DYN reversibly
      reduced, in a naloxone-sensitive manner, calcium currents in acutely dissociated
      rat nodose ganglion neurons. DYN slowed the rate of current activation and had a
      greater effect on currents evoked from relatively negative holding potentials.
      These actions were mimicked by guanosine 5'-[gamma-thio]triphosphate, which
      activates GTP-binding proteins (G proteins), and were blocked by pretreatment
      with pertussis toxin, which inactivates Gi- and Go-type G proteins. In contrast,
      calcium currents recorded in the presence of the catalytic subunit of the cAMP
      dependent protein kinase (AK-C), included in the recording pipette, increased in
      magnitude throughout the recording. DYN was applied to neurons before and after
      the effect of AK-C became apparent; the reduction of calcium currents by DYN was
      greater in the presence of AK-C than in its absence. We conclude that the acute
      reduction of neuronal calcium currents by DYN occurred by means of activation of
      pertussis toxin-sensitive Gi- or Go-type G proteins. The persistence of the
      action of DYN in the presence of AK-C indicates, however, that this effect was
      independent of a reduction of the activity of the adenylate cyclase/cAMP system
      and suggests in addition that phosphorylated channels may be preferentially
      inhibited by DYN.

PMID- 1976251
TI  - Intimate association of Thy-1 and the T-cell antigen receptor with the CD45
      tyrosine phosphatase.
AB  - Immunoprecipitation of Thy-1 from Triton X-100 detergent lysates of surface
      iodinated and chemically cross-linked T cells precipitated at least five major
      and discrete bands. Four of these bands were identified as Thy-1, CD45 (a
      transmembrane tyrosine phosphatase), a major histocompatibility complex-encoded
      class I molecule, and beta 2-microglobulin. Similar analyses revealed that CD45
      was coprecipitated from lysates of cross-linker-treated cells by antibodies to
      the T-cell antigen receptor (TCR). The same pattern of coprecipitated bands was
      observed when digitonin was used to lyse untreated cells. Immunoprecipitation of
      Thy-1 or the TCR from lysates of cross-linked T cells precipitated CD45 tyrosine
      phosphatase activity. Calculations based upon the amounts of coprecipitated
      enzymatic activity or TCR zeta chain indicate that a substantial fraction of Thy
      1 and TCR complexes can be cross-linked to CD45. These data support a model in
      which the dependence of Thy-1 signaling on TCR coexpression is due to their
      common interaction with a tyrosine phosphatase and provide a possible structural
      basis for the influence of CD45 on TCR-mediated signaling.

PMID- 1976253
TI  - Failure to reverse long-term potentiation by coupling sustained presynaptic
      activity and N-methyl-D-aspartate receptor blockade.
AB  - The proposal that long-term potentiation (LTP) is a mechanism underlying memory
      in the mammalian brain rests on a number of properties of LTP that parallel
      characteristics of memory defined by behavior. A prominent feature of
      behaviorally defined memory is its reversibility. LTP is induced at synapses that
      correlate in their activity, and the signal for induction is calcium influx
      through N-methyl-D-aspartate (NMDA) receptor channels. By analogy to the
      reversibility of behaviorially defined memory, uncorrelated synaptic activity
      might be expected to reverse LTP, an anti-Hebbian effect called long-term
      depression, which has only recently been described in the hippocampus [Stanton,
      P. K. & Sejnowski, T. J. (1989) Nature (London) 339, 215-218]. Because the extent
      to which synaptic activity is correlated is represented by postsynaptic calcium
      concentrations, it seemed likely to us that long-term depression is related to
      the failure of calcium to pass through the NMDA channel. One way to block the
      calcium influx that signals correlated synaptic activity is with the NMDA
      receptor antagonist D-(-)-2-amino-5-phosphonovalerate. We performed a series of
      experiments in rat hippocampal slices designed to estimate the amount of synaptic
      depression per afferent test pulse under these conditions. Schaffer collateral
      commissural afferents to field CA1 were repetitively stimulated in the presence
      of 2-amino-5-phosphonovalerate. No enduring synaptic depression nor reversal of
      LTP could be detected. We conclude that some other mechanism underlies long-term
      depression in the hippocampus.

PMID- 1976252
TI  - Quantitative analysis of MDR1 (multidrug resistance) gene expression in human
      tumors by polymerase chain reaction.
AB  - The resistance of tumor cells to chemotherapeutic drugs is a major obstacle to
      successful cancer chemotherapy. In human cells, expression of the MDR1 gene,
      encoding a transmembrane efflux pump (P-glycoprotein), leads to decreased
      intracellular accumulation and resistance to a variety of lipophilic drugs
      (multidrug resistance; MDR). The levels of MDR in cell lines selected in vitro
      have been shown to correlate with the steady-state levels of MDR1 mRNA and P
      glycoprotein. In cells with a severalfold increase in cellular drug resistance,
      MDR1 expression levels are close to the limits of detection by conventional
      assays. MDR1 expression has been frequently observed in human tumors after
      chemotherapy and in some but not all types of clinically refractory tumors
      untreated with chemotherapeutic drugs. We have devised a highly sensitive,
      specific, and quantitative protocol for measuring the levels of MDR1 mRNA in
      clinical samples, based on the polymerase chain reaction. We have used this assay
      to measure MDR1 gene expression in MDR cell lines and greater than 300 normal
      tissues, tumor-derived cell lines, and clinical specimens of untreated tumors of
      the types in which MDR1 expression was rarely observed by standard assays. Low
      levels of MDR1 expression were found by polymerase chain reaction in most solid
      tumors and leukemias tested. The frequency of samples without detectable MDR1
      expression varied among different types of tumors; MDR1-negative samples were
      most common among tumor types known to be relatively responsive to chemotherapy.

PMID- 1976254
TI  - Dominant mutations causing alterations in acetyl-coenzyme A carboxylase confer
      tolerance to cyclohexanedione and aryloxyphenoxypropionate herbicides in maize.
AB  - A partially dominant mutation exhibiting increased tolerance to cyclohexanedione
      and aryloxyphenoxypropionate herbicides was isolated by exposing susceptible
      maize (Zea mays) tissue cultures to increasingly inhibitory concentrations of
      sethoxydim (a cyclohexanedione). The selected tissue culture (S2) was greater
      than 40-fold more tolerant to sethoxydim and 20-fold more tolerant to haloxyfop
      (an aryloxyphenoxypropionate) than the nonselected wild-type tissue culture.
      Regenerated S2 plants were heterozygous for the mutant allele and exhibited a
      high-level, but not complete, tolerance to both herbicides. Homozygous mutant
      families derived by self-pollinating the regenerated S2 plants exhibited no
      injury after treatment with 0.8 kg of sethoxydim per ha, which was greater than
      16-fold the rate lethal to wild-type plants. Acetyl-coenzyme A carboxylase
      (ACCase; EC 6.4.1.2) is the target enzyme of cyclohexanedione and
      aryloxyphenoxypropionate herbicides. ACCase activities of the nonselected wild
      type and homozygous mutant seedlings were similar in the absence of herbicide.
      ACCase activity from homozygous tolerant plants required greater than 100-fold
      more sethoxydim and 16-fold more haloxyfop for 50% inhibition than ACCase from
      wild-type plants. These results indicate that tolerance to sethoxydim and
      haloxyfop is controlled by a partially dominant nuclear mutation encoding a
      herbicide-insensitive alteration in maize ACCase.

PMID- 1976255
TI  - Molecular basis of preferential resistance to colchicine in multidrug-resistant
      human cells conferred by Gly-185----Val-185 substitution in P-glycoprotein.
AB  - Expression of P-glycoprotein, encoded by the human MDR1 gene, results in cross
      resistance to many lipophilic cytotoxic drugs (multidrug resistance). P
      glycoprotein is believed to function as an energy-dependent efflux pump that is
      responsible for decreased drug accumulation in multidrug-resistant cells.
      Previous work showed that preferential resistance to colchicine in a colchicine
      selected multidrug-resistant cell line was caused by spontaneous mutations in the
      MDR1 gene that resulted in a Gly-185----Val-185 substitution in P-glycoprotein.
      We have now compared transfectant cell lines expressing either the wild-type Gly
      185 or the mutant Val-185 P-glycoprotein with regard to their levels of
      resistance to and accumulation and binding of different drugs. In cells
      expressing the mutant protein, increased resistance to colchicine and decreased
      resistance to vinblastine correlated with a decreased accumulation of colchicine
      and increased accumulation of vinblastine. Expression of the mutant P
      glycoprotein also resulted in significantly increased resistance to
      epipodophyllotoxin and decreased resistance to vincristine and actinomycin D;
      smaller changes in resistance were observed for several other drugs.
      Unexpectedly, the mutant P-glycoprotein showed increased binding of photoactive
      analogs of vinblastine and verapamil and the photoactive compound azidopine and
      decreased binding of a photoactive colchicine analog. These results suggest that
      the Gly-185----Val-185 substitution affects not the initial drug-binding site of
      P-glycoprotein but another site, associated with the release of P-glycoprotein
      bound drugs to the outside of the cell.

PMID- 1976257
TI  - Culture of purified pluripotent haemopoietic stem cells.

PMID- 1976259
TI  - Bone marrow proliferation after passage through an irradiated host.

PMID- 1976258
TI  - The combination of IL-3 and IL-6 enhances retrovirus mediated gene transfer into
      hematopoietic stem cells.

PMID- 1976256
TI  - Association of intercellular adhesion molecule 1 with the multichain high
      affinity interleukin 2 receptor.
AB  - Previously, using flow cytometric resonance energy transfer and lateral diffusion
      measurements, we demonstrated that a 95-kDa protein identified by two monoclonal
      antibodies (OKT27 and OKT27b) interacts physically with the 55-kDa alpha protein
      of the high-affinity interleukin 2 (IL-2) receptor. In the present study, this 95
      kDa protein (p95) was purified and amino acid sequence data were obtained that
      showed strong homology to the human intercellular adhesion molecule 1 (ICAM-1).
      The identity of the p95 protein with ICAM-1 was confirmed by sequential
      immunoprecipitations using OKT27 and an antibody, WEHI-CAM-1, that is directed
      toward ICAM-1. We confirmed the physical proximity of p95/ICAM-1 to the IL-2
      receptor alpha subunit by demonstrating that radiolabeled IL-2 could be cross
      linked to this protein expressed on activated T cells. In functional studies, the
      antibodies OKT27 and OKT27b inhibited T-cell proliferative responses to OKT3, to
      soluble antigen, and to heterologous cells (mixed lymphocyte reaction). However,
      these antibodies did not inhibit IL-2-induced proliferation of an IL-2-dependent
      T-cell line. Taken together with our previous observations, the present studies
      suggest that ICAM-1 is in proximity and interacts physically with the high
      affinity IL-2 receptor. The association of ICAM-1 with the IL-2 receptor may
      facilitate the paracrine IL-2-mediated stimulation of T cells expressing IL-2
      receptors by augmenting homotypic T-T-cell interaction, by receptor-directed
      focusing of IL-2 release by helper T cells, and by focusing IL-2 receptors of the
      physically linked cells to the site of lymphocyte function-associated antigen 1
      ICAM-1-IL-2 receptor interaction.

PMID- 1976260
TI  - Prediction of clinical outcome of radiation accident victims.
AB  - On the basis of the analysis of more than 350 individuals that were exposed to
      ionizing radiation in the course of more than 25 radiation accidents reported
      world wide since 1945, a biomathematical computer model was developed that
      simulates the pattern of granulocyte changes seen. It allows one to calculate the
      number of stem cells remaining intact to initiate recovery. It is shown that the
      major question to be asked is whether a spontaneous stem cell recovery can be
      expected or not. This question can be readily answered within 3-5 days after
      radiation exposure on the basis of the constellation of hematopoietic findings
      and devised stem cell pool size calculations.

PMID- 1976261
TI  - Molecular mechanism of hematopoietic stem cell binding to the supportive stroma.

PMID- 1976262
TI  - [Synthesis and alpha-adrenolytic activities of 2-(1,4-benzodioxan-2-yl- methyl)
      6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivatives].
AB  - The synthesis of the title compounds starting from 2-Chlormethylbenzdioxan and
      Tetrahydroisochinolines is presented. Their actions on the platelet aggregation
      and the inhibition of alpha-adrenoceptors at the isolated rabbit aorta and the
      vas deferens of the guinea pig were investigated.

PMID- 1976264
TI  - Migrant pests: problems, potentialities and progress.

PMID- 1976263
TI  - Regression estimation from grouped observations applied to structurally diverse
      D2-receptor antagonists.
AB  - Four groups of chemically diverse dopamine D2-receptor antagonists with different
      group size were studied. The total sample consisted of a mixture of distributions
      with some influential observations, and the grouped data were characterized by
      different dispersion matrices but equal mean vectors. Thus, it was difficult to
      employ pattern recognition approaches. Design repair was used to develop a
      quantitative structure-activity relationship equation. It was shown that the
      inhibition constant of all groups depends on the true lipophilic constant.

PMID- 1976265
TI  - The WHO Onchocerciasis Control Programme: retrospect and prospects.
AB  - The history of onchocerciasis control in Africa and the genesis of the WHO
      Onchocerciasis Control Programme in West Africa (OCP) are briefly reviewed. The
      importance of experience gained in anti-locust campaigns in helping to plan the
      OCP is stressed. Members of the Simulium damnosum species complex are the vectors
      of onchocerciasis, which OCP is controlling with insecticide treatments on the
      stretches of rivers where the Simulium breed. Migrations of flies have been
      responsible for reinfestations of controlled areas and the spread of insecticide
      resistance. The management of these problems and related research are described,
      but it is emphasized that despite setbacks OCP is achieving its aims. A strategy
      for the future is outlined: vector control supplemented by chemotherapy is
      expected to continue until the year 2004.

PMID- 1976266
TI  - Progress in controlling the reinvasion of windborne vectors into the western area
      of the Onchocerciasis Control Programme in West Africa.
AB  - Since vector control began in 1975, waves of Simulium sirbanum and S. damnosum
      s.str., the principal vectors of severe blinding onchocerciasis in the West
      African savannas, have reinvaded treated rivers inside the original boundaries of
      the Onchocerciasis Control Programme in West Africa. Larviciding of potential
      source breeding sites has shown that these 'savanna' species are capable of
      travelling and carrying Onchocerca infection for at least 500 km northeastwards
      with the monsoon winds in the early rainy season. Vector control has, therefore,
      been extended progressively westwards. In 1984 the Programme embarked on a major
      western extension into Guinea, Sierra Leone, western Mali, Senegal and Guinea
      Bissau. The transmission resulting from the reinvasion of northern Cote d'Ivoire
      and Burkina Faso has been reduced by over 95%, but eastern Mali has proved more
      difficult to protect because of sources in both Guinea and Sierra Leone. Rivers
      in Sierra Leone were treated for the first time in 1989 and biting and
      transmission rates in Sierra Leone and Guinea fell by over 90%. Because of
      treatment problems in some complex rapids and mountainous areas, flies still
      reinvaded Mali, though biting rates were approximately 70% lower than those
      recorded before anti-reinvasion treatments started. It was concluded that
      transmission in eastern Mali has now been reduced to the levels required to
      control onchocerciasis.

PMID- 1976267
TI  - Optimum take-off techniques for high and long jumps.
AB  - High jumpers run at moderate speeds and set down the foot, from which they take
      off, well in front of the body. Long jumpers run up much faster and place the
      foot less far forward, with the leg at a steeper angle. A simple model, which
      takes into account the mechanical properties of muscle, predicts optimum take-off
      techniques that agree well with those used by athletes. These predictions are
      remarkably insensitive to the numerical values assigned to the physiological
      parameters.

PMID- 1976268
TI  - [Neuroleptic malignant syndrome--3 case reports].
AB  - An account is given of three patients who exhibited a malignant neuroleptic
      syndrome after the administration of neuroplegics. Like other authors, we
      identified typical elicitation factors and clinical characteristics. In one case
      a catatonic dilemma with lethal issue was observed. In the final case dealt with
      in this paper, the renewed application of neuroplegics following the termination
      of the malignant neuroleptic syndrome was tolerated without complications,
      whereas in the case of an epileptic patient with damage to the brain, the
      malignant neuroleptic syndrome returned upon dosage increase.

PMID- 1976269
TI  - [Alzheimer's disease amyloid A4(beta) protein].

PMID- 1976270
TI  - Pattern of acid reflux in patients with reflux esophagitis 'resistant' to H2
      receptor antagonists.
AB  - Ambulatory 24-h esophageal pH monitoring was carried out in 54 patients with
      erosive/ulcerative reflux esophagitis before a 12- to 24-week treatment with
      either ranitidine, 150 to 300 mg twice daily, or famotidine, 20 to 40 mg twice
      daily. After this period, 21 patients continued to present endoscopic evidence of
      esophagitis. Patients who did not respond to the therapy showed a more severe
      pretreatment pattern of acid reflux than those who healed, with regard to both
      median percentage time of reflux (16.2% versus 11.0%, respectively, p less than
      0.05) and median number of reflux episodes (88.0 versus 55.0; p less than 0.05).
      Ambulatory 24-h esophageal pH-metry is therefore to be recommended in all
      patients with acid reflux symptoms, even in those who already show endoscopic
      lesions of the esophageal mucosa, since this test is a valid prognostic indicator
      of response to treatment.

PMID- 1976272
TI  - [Somatostatin and seizures].

PMID- 1976271
TI  - Prostaglandins and peptic ulcer therapy.
AB  - The expectation that prostaglandin analogues would improve the ulcer healing
      abilities of other agents by combining mucosal protection with decreased acid
      secretion has been proved unwarranted. The ulcer healing capabilities of these
      drugs reflect their antisecretory potency. A role for these drugs in ulcer
      healing is questionable but their use has been advocated most strongly to prevent
      ulceration developing during treatment with non-steroidal anti-inflammatory
      drugs. While some evidence supports this role, an important clinical benefit of
      reducing complication rates has yet to be demonstrated.

PMID- 1976274
TI  - Morphological studies on the larval stages of three species of Setaria and
      Dirofilaria repens.
AB  - This paper reports for the first time the morphology of larval stages of Setaria
      labiato-papillosa. The infective larvae of this species had two circles of small
      papillae on the cephalic end, 4 papillae for outer circle and 6 for inner circle.
      The caudal end of S. labiato-papillosa is in digital form with 3 transversally
      arranged papillae. There are 2 circles of small papillae on the cephalic end of
      S. leichungwingi and S. equina, 4 for each circle; the caudal terminal of the
      former species is willow-shaped with 3 pearl-like papillae, and that of the
      latter is conical shaped with 1 bulbed papilla, 2 slightly protruded papillae at
      sub-terminal. The anal ratios of all the above 3 species are below 3. Morphology
      of larval stages of Dirofilaria repens was also primarily described in China. The
      3 bulbed caudal papillae of the infective larvae are closely arranged, and the
      anal ratio being less than 2. A key to infective larvae of 8 species of filaria
      was worked out according to relevant literature and the present study.

PMID- 1976273
TI  - Scanning electron microscopy of the eggs of Mansonia uniformis, Ma. indiana and
      Ma. annulifera (Diptera: Culicidae).
AB  - Descriptions of the eggs of Mansonia uniformis, Ma. indiana and Ma. annulifera
      are provided with the aid of scanning electron micrographs. Eggs of these three
      species, although similar in shape and colour, are covered by outer chorionic
      reticulum and tubercles which provide reliable morphological character for their
      identification. Size, distribution and number of lobes on the large tubercles
      present in the region between the anterior tube and posterior region, are
      important distinguishing features. Measurements of egg sizes and other chorionic
      differences are also discussed.

PMID- 1976275
TI  - [Congress 1990. Danish Nurses' Council].

PMID- 1976276
TI  - Restriction fragment length polymorphism of complement C4 in Japanese patients
      with rheumatoid arthritis and normal Japanese.
AB  - Restriction fragment length polymorphism (RFLP) of the two genes for complement
      C4A and C4B was studied in 56 Japanese patients with rheumatoid arthritis (RA)
      and 161 normal individuals. HindIII digestion revealed six common patterns, from
      which the segregation of three common RFLP-types were deduced; 32-15 kb, 32-25
      kb, and 32-20-13-6.5 kb. The last type showed positive associations with C4B5 and
      HLA-DR4. In the RA patients, an increase of this type was found as well as a
      decrease of the 32-15 kb/32-25-15 kb heterozygotes.

PMID- 1976277
TI  - Restriction fragment length polymorphism of a lymphocyte surface antigen, Blast
      1, in Japanese and Caucasians, and in patients with rheumatoid arthritis.
AB  - Analysis of polymorphic systems, demonstrating differences among ethnic groups,
      provides a valuable tool for biology and medicine. Blast-1 is a member of the
      immunoglobulin superfamily and an activation-associated glycoprotein expressed on
      the surface of mononuclear cells. Blast-1 demonstrates DNA polymorphism in
      healthy controls and patients with rheumatoid arthritis (RA). The sizes of
      polymorphic restriction endonuclease fragments of genomic DNA encoding Blast-1
      were 2.4 and 1.9 kb. In normal controls, the frequency of the homozygote for the
      2.4 kb fragment (L-L) was 0.69 and 0.47, and that for the 1.9 kb fragment (S-S)
      was 0.04 and 0.11 in Caucasians and Japanese, respectively. The frequency of the
      heterozygote for both fragments (L-S) was 0.27 and 0.42 in Caucasians and
      Japanese, respectively. The frequencies of the L and S alleles were 0.83 and 0.17
      for Caucasians, respectively, and were 0.68 and 0.32 for Japanese, respectively.
      The difference in the allele frequency between Caucasians and Japanese was
      significant. In Japanese patients with RA, the frequency of L-L, L-S and S-S
      types was 0.45, 0.45 and 0.10, respectively. Lung fibrosis in Japanese RA
      patients was associated with an increase in the L-S and S-S types and a decrease
      in the L-L type. The present study indicates that the investigation for gene
      polymorphisms of Blast-1 among distinct ethnic groups is important because Blast
      1 appears to be a genetic marker for the manifestation associated with RA.

PMID- 1976278
TI  - Shared SstI RFLPs by HLA-Aw19, A23/24 and A3/11 crossreacting groups.
AB  - Three novel restriction fragment length polymorphisms (RFLPs) have been
      identified using a pan-HLA class I probe and the endonuclease SstI. This study,
      in conjunction with previously reported SstI RFLPs, now allows the identification
      of the HLA-crossreacting antigens Aw19 (A29/30/31/32/w33), A23/24 and A3/11 by
      specific hybridization patterns with a single enzyme/probe combination. Three of
      the corresponding polymorphic SstI restriction sites map within the HLA-A gene
      and generate two allelic RFLPs (5.06, 5.92 kb) and one single RFLP (5.92 kb) that
      show an absolute correlation with HLA-A23/24 and A29/32 crossreacting antigens,
      respectively. However, other SstI RFLPs (7.97, 9.4, 9.6, 9.8 and 13.34 kb), also
      linked to HLA-A crossreacting antigens, map outside the HLA-A gene and probably
      correspond to non-HLA-A,B,C class I genes in strong linkage disequilibrium with
      the HLA-A gene. These data show that HLA-A crossreacting antigens share more SstI
      RFLPs than neighboring non-HLA-A,B,C class I genes or pseudogenes; also, this has
      raised the possibility that some crossreacting HLA-A alloantisera might
      additionally recognize shared antigenic determinants in non-HLA-A,B,C proteins
      since the HLA-Aw19 crossreactivity cannot be fully explained by analyzing the HLA
      A amino acid sequence.

PMID- 1976279
TI  - Biochemical and pharmacological studies of the mechanism of action of tenebrosin
      C, a cardiac stimulatory and haemolytic protein from the sea anemone, Actinia
      tenebrosa.
AB  - Tenebrosin-C is a protein of mol. wt 19,500 that displays potent cardiac
      stimulatory and haemolytic activities. Its haemolytic activity is inhibited by
      sphingomyelin but not phosphatidylcholine, and is not affected by Ca2+. The
      positive inotropic effect of tenebrosin-C on isolated guinea pig right atria is
      inhibited by the cyclooxygenase blockers indomethacin and aspirin, the
      lipoxygenase blocker and leukotriene antagonist RG5901, and the phospholipase A2
      inhibitor mepacrine. This activity of tenebrosin-C therefore appears to be due to
      stimulation of the release of arachidonic acid and subsequent formation of
      prostaglandins and leukotrienes. Phospholipase A2-like activity was found with
      some tenebrosin-C preparations, but did not correlate with their positive
      inotropic or haemolytic activities and was too weak to account for either of
      these effects. Treatment of tenebrosin-C with various proteases in order to
      obtain active fragments showed that the protein is remarkably resistant to
      proteolysis.

PMID- 1976280
TI  - Prolonged blurred vision following coelenterate envenomation.
AB  - The case history of a healthy woman who developed persistent (8 days) blurred
      vision within 3 hr of a jellyfish (Linuche unguiculata) sting on her knee is
      reported. Persistent sequelae following envenomation by marine animals can occur
      but are unusual.

PMID- 1976281
TI  - Parentage analysis by endonuclease shattering of hypervariable DNA.
AB  - Single-locus DNA probes for tandem repeat sequences are now used in conjunction
      with particular endonucleases to characterize heritable restriction fragment
      lengths in parentage tests. Southern blots of this type, however, demonstrate
      only two attributes of an allele: its length and the presence of nucleotide
      sequences that are complementary to the probe. Not all restriction fragments of
      the same apparent length that react with the same probe are identical.
      Differences between comigrating fragments can be detected by the selection of a
      restriction enzyme that recognizes sites in a subset of the repeat sequences, and
      the information content of these loci is therefore increased. This report
      describes a paternity case in which two brothers appeared, after DNA phenotyping
      using Hinf I, to be the father. A second phenotyping using Hae III excluded one
      of the brothers.

PMID- 1976282
TI  - Induction of donor-specific unresponsiveness to cardiac allografts in rats by
      pretransplant anti-CD4 monoclonal antibody therapy.
AB  - In the present report a monoclonal antibody designated OX-38 directed against the
      rat CD4 molecule was tested for its ability to prolong the survival of
      heterotopic vascularized rat heart allografts transplanted across major
      histocompatibility barriers. Fluorescence-activated cell-sorter analysis showed
      that administration of OX-38 selectively depleted 80-95% of CD4+ cells from
      peripheral blood of treated rats. The immunosuppressive effects of OX-38 in vivo
      were verified by suppression of an antibody response against OX-38 itself as a
      heterologous protein immunogen. Recipient rats received OX-38 antibody as a
      single agent given in pretransplant regimens. Nine of 12 treated rats have
      maintained heterotopic abdominal heart allografts for greater than 175 days.
      Control rats that did not receive antibody therapy rejected their grafts within
      14 days. Rats that maintained heart allografts for greater than 100 days accepted
      second donor strain hearts but rejected third-party heart grafts transplanted
      into the femoral space. Anti-CD4-induced allograft unresponsiveness persisted for
      at least 90 days following surgical removal of donor tissue and retransplantation
      of a second donor-matched heart. These results indicated that transient,
      pretransplant therapy with monoclonal antibodies directed against the CD4+
      lymphocyte induced specific, long-lasting unresponsiveness to fully MHC
      mismatched cardiac allografts in rats without additional immunosuppression.

PMID- 1976284
TI  - An alternative method of assessment of HLA incompatibilities in kidney grafts.

PMID- 1976283
TI  - Specific unresponsiveness in rats with prolonged cardiac allograft survival after
      treatment with cyclosporine. IV. Examination of T cell subsets in graft-versus
      host assays.
AB  - In DA rats grafted with PVG hearts a short course of cyclosporine induces a state
      of specific unresponsiveness. In animals with grafts surviving greater than 75
      days, the W3/25+ (CD4+) subset loses its capacity to mediate rejection of PVG but
      not third-party heart grafts when transferred into irradiated DA hosts. In this
      study we examined whether there was an associated change in the capacity of
      peripheral lymphoid T cell subsets from unresponsive animals to induce graft
      versus host (GVH) reactivity. First we demonstrated that there is synergy between
      naive CD4+ and CD8+ cells in the popliteal lymph node PLN assay, but that alone,
      only CD4+ and not CD8+ cells proliferate. Unfractionated and CD4+ cells from
      unresponsive animals produced similar PLN enlargement in both donor-specific
      (DAxPVG)F1 hosts and third-party (W/FxDA)F1 hosts. This enlargement was
      comparable to that produced cells from naive and specifically sensitized hosts.
      MRC OX8+ cells from both unresponsive and naive hosts did not produce PLN
      enlargement unless large numbers were injected; small numbers of sensitized MRC
      OX8+ cells produced specific PLN enlargement CD4+ cells from CsA-treated DA did
      not respond to DA anti-PVG idiotype in an in vivo assay adapted from the host
      versus graft (HVG) PLN assay. As the PLN assay does not test cells capacity to
      effect tissue damage, cells from CsA-treated DA rats were tested in a lethal GVHD
      assay. These cells had the same capacity to induce lethal GVH in irradiated
      (DAxPVG)F1 and (DAxW/F)F1 hosts. The normal response of cells from unresponsive
      animals in both proliferative and effector GVH assays shows that cells with the
      potential to respond to PVG alloantigen and mediate tissue damage are present in
      unresponsive animals but are prevented from mediating rejection, possibly due to
      the relatively weak immune stimulus of an organ graft.

PMID- 1976285
TI  - [Should chronic atrial fibrillation be treated with digoxin?].
AB  - For decades, atrial fibrillation was treated exclusively with digoxin. The
      introduction of Ca-antagonists and beta-blockers has, however, produced valuable
      alternatives as ventricular function can now be controlled both at rest and
      during exercise whereas, with digoxin, ventricular function could only be
      controlled at rest. This review deals with the etiology and electrophysiology of
      atrial fibrillation together with the effects of Ca-antagonists and beta-blockers
      on conduction and control of the heart rate during exercise. Documentation of the
      effects of the different drugs, separately and combined, in the treatment of
      atrial fibrillation during rest and exercise is presented. It is concluded that
      alteration in the therapeutic strategy appears reasonable in favour of a
      combination of digoxin and also Ca-antagonists/beta-blocker.

PMID- 1976286
TI  - Bovine spongiform encephalopathy: detection and quantitation of fibrils, fibril
      protein (PrP) and vacuolation in brain.
AB  - Bovine spongiform encephalopathy (BSE) is a new disease of cattle which has
      considerable homology with scrapie, the archetype of the transmissible spongiform
      encephalopathies. Abnormal brain fibrils, called scrapie associated fibrils
      (SAF), are specific ultrastructural markers for these diseases. Fibril detection
      was compared with histopathological diagnosis in the brains of 167 cattle; 157
      clinically suspect BSE and 10 clinically normal. Fibrils were detected in samples
      of pooled brain regions of 67/144 in which vacuolar changes of BSE were
      confirmed, but absent in the remaining 23 brains, in which no vacuolation was
      found, including those from the clinically normal cattle and 13 with alternative
      neuropathological diagnoses. When eight defined anatomic regions from the brains
      of another 22 affected cows were examined, the sensitivity of fibril detection
      was greater than 90% for the brain stem areas. Fibril prevalence in these areas
      approximated to severity of vacuolar changes. When the same defined regions from
      four of the affected cows were assayed for fibril protein (PrP) by western
      blotting, the density of immuno-labelling generally correlated with the fibril
      prevalence. This study confirms the specificity of fibril detection for BSE,
      shows that the ease of fibril detection depends on anatomic region sampled and
      suggests an association between PrP accumulation and vacuolar changes in certain
      neuroanatomic areas.

PMID- 1976288
TI  - [Effects of alpha-adrenoceptor agonists on cardiac function and blood pressure in
      rats].
AB  - In rat working hearts, alpha 1-adrenoceptor agonist phenylephrine increased LVP,
      +/- dP/dtmax, ABF and HR in the presence of propranolol. But alpha 2-adrenoceptor
      agonist B-HT 920 was ineffective. The changes induced by phenylephrine were
      antagonized by prazosin. In normotensive pithed rats, iv methoxamine dose
      dependently increased LVP, +/- dP/dtmax, LVEDP, SAP and DAP. The changes in
      haemodynamics elicited by iv methoxamine were also antagonized by pretreatment
      with prazosin, and were attenuated by nifedipine (1 mg/kg, ia). In these two
      experiments, the increase in HR developed more slowly. The results suggest that
      postjunctional alpha 1-adrenoceptors, which exist in rat myocardium, produce a
      positive inotropic effect, which is possibly dependent on influx of extracellular
      calcium. Postjunctional alpha 2-adrenoceptors-mediated effects were not found in
      rat myocardium in our functional studies.

PMID- 1976287
TI  - [The diagnostic importance of research on the lysyl oxidase activity in children
      with circumscribed scleroderma].
AB  - Blood serum lysyl oxidase activity considerably varies, these variations
      correlating with the skin process dissemination, in children suffering from focal
      scleroderma. This enzyme was undetectable in normal subjects and patients with
      dermatoses whose clinical symptoms are similar to those of focal scleroderma.
      Blood serum lysyl oxidase activity elevation is a specific sign, characteristic
      of patients with focal scleroderma; it therefore may be used for the laboratory
      diagnosis of this dermatosis, assessment of its dissemination and severity.

PMID- 1976289
TI  - [Therapeutic effect of methyl 5-aminosalicylate on experimental ulcerative
      colitis in rabbits].
AB  - Using the improved Kirsner model of ulcerative colitis in rabbits, we found that
      the therapeutic effect of methyl 5-amino salicylate hydrochloride (M-5-AS) was
      similar to that of sulfasalazine (salicylazosulfapyridine, SZ). The length of
      pathological damage and the range of diffuse ulcers were decreased in comparison
      with the control group (P less than 0.01, 0.05). Microscopically, tissue
      repairing at the regions of ulcers and proliferation in serolemma were noted, and
      the edema in muscular mesenchyme was less evident in the treated rabbits. M-5-AS
      completely inhibited the spontaneous contraction of rat stomach fundus strips and
      colon. The IC50 of the resting tone of the 2 tissues were 1.30 +/- 0.39 and 0.72
      +/- 0.25 mmol/L, respectively. In addition, M-5-AS antagonized the contraction
      induced by human fresh semen. The results suggest that the therapeutic mechanism
      is related to the antagonism of prostaglandins in the inflammatory regions.

PMID- 1976290
TI  - Neuropathological and enzymatic studies in a case of adult form of metachromatic
      leukodystrophy with very late onset of clinical symptoms.
AB  - Metachromatic leukodystrophy is a genetical disorder due to a deficiency of
      arylsulphatase A activity. According to the age of onset of symptoms three
      different forms of the disease are described: late infantile, juvenile and adult
      types. We report the clinical, neuroimaging, biochemical and morphological
      features in a man in which the first symptoms ensued at the age of 39. In this
      patient, whose clinical manifestations were represented by "psychiatric"
      symptoms, the onset was particularly late in comparison with the large majority
      of the previously reported cases.

PMID- 1976291
TI  - Structural characteristics of compounds that modulate P-glycoprotein-associated
      multidrug resistance.
AB  - Multidrug resistance is mediated by a membrane-bound protein, P-gp, that
      functions as an energy dependent efflux system to reduce the intracellular
      concentration of anticancer drugs by binding to these drugs and actively
      exporting them from the cell. Compounds that interact with P-gp and compete with
      anticancer drug binding modulate the degree of drug resistance and therefore
      enhance the cytotoxicity of anticancer drugs against the resistant cell.
      Effective modulators share certain physical and chemical properties including
      octanol/water partitioning and molecular size, but the physical properties of
      size and shape seem to correlate best with modulator effectiveness. Using a
      photoactivatable analog of vinblastine as a probe, together with a semi-synthetic
      series of structurally homologous reserpine and yohimbine analogs, the need for
      two planar aromatic domains and a basic nitrogen atom was established within the
      structural context of these compounds. The use of three-dimensional comparisons
      was extended to examine important structural features in other modulator types
      such as the condensed-ring aromatics. This approach indicates that structural
      similarities between different classes of compounds are present in compounds
      recognized by the MDR phenotype. These studies emphasize the importance of a
      ligand-receptor relationship for modulators of MDR, and begin to define the P-gp
      binding pharmacophore. It is likely that this approach will be useful in
      directing the de novo synthesis of compounds that modulate MDR and help to
      further define the requirements for molecular recognition by this system.

PMID- 1976292
TI  - Hormonal control of specific gene expression in the rat liver during the suckling
      weaning transition.
AB  - In the rat, the suckling-weaning transition is accompanied by marked changes in
      nutrition. During the suckling period, the pups are fed with milk which is a high
      fat low-carbohydrate diet. At weaning, milk is progressively replaced by the rat
      chow which is a high-carbohydrate low-fat diet. This is accompanied by
      considerable hormonal modifications: an increase in plasma insulin and a decrease
      in plasma glucagon concentrations, as well as by marked changes in metabolic
      pathways in liver: decrease in hepatic gluconeogenesis, increase in lipogenesis,
      and appearance of liver glucokinase. Most of the data concerning these changes
      are related to maximal activity of enzymes. The recent availability of specific
      cDNA probes for phosphoenolpyruvate carboxykinase, acetyl-CoA carboxylase, fatty
      acid synthase and glucokinase has allowed study of the role of pancreatic
      hormones and of nutrition in the changes of the expression of these genes at
      weaning in the rat.

PMID- 1976293
TI  - Prologue: agricultural occupational and environmental health: policy strategies
      for the future.
AB  - The conference "Agricultural Occupational and Environmental Health: Policy
      Strategies for the Future" documented for the public record the epidemic of
      occupational and environmental deaths, diseases, and injuries experienced by
      America's farm families and agricultural workers. The conference also gave life
      to a process aimed at reducing those hazards. The outcome of long-range
      objectives of lowering death, injury, and disease rates in our agricultural
      population will not be known for several years. However, there was unanimous
      consensus that the major short-range objectives were achieved. Extensive regional
      and national media coverage helped meet the goal of facilitating public awareness
      of the issues. In addition, a prioritized policy agenda, soundly based on recent
      scientific information, was produced. This agenda was the product of
      collaboration between the scientific community, farm constituency groups, farm
      equipment and chemical manufacturers, and representatives from state and federal
      governments. Primary changes resulting from the conference include an increase in
      general awareness and a sense of urgency that agricultural health problems must
      be addressed. In addition, the conference spawned a new organization called the
      National Coalition for Agricultural Safety and Health (N-CASH) to help assure a
      vibrant continuation of conference issues. This coalition will live on to help
      disseminate the spirit, information, and specific policy recommendations of the
      conference to the public sector and private institutions. Two years of planning
      and work by 18 individuals occurred even before the start of the conference.
      During the conference, 176 individuals put in an equivalent of three and a half
      person years of work. However, the work is just beginning. This effort is
      justified if it results in one less death or serious injury in a farm family.

PMID- 1976294
TI  - Prostaglandins and gastric ulcers: from seminal vesicle to misoprostol (Cytotec).
AB  - Misoprostol (Cytotec, G.D. Searle & Company, Chicago, IL) is the first of a new
      class of orally administered prostaglandin analog drugs to be marketed in the
      United States. Misoprostol was approved for the prevention of gastric mucosal
      ulcers associated with nonsteroidal anti-inflammatory drugs (NSAIDS) in high-risk
      patients. This represents a potentially important development in the
      pharmacotherapy of peptic ulcer disease. The purposes of this article are to
      review (1) the biochemistry, physiology, and pharmacology of prostaglandins,
      especially those synthesized by the stomach; (2) the potential role of
      prostaglandin deficiency in the pathophysiology of gastric ulcer disease; and (3)
      the role of prostaglandin analogs in the prevention and therapy of gastric ulcer
      disease and in other conditions. As the mechanism of action of these new drugs
      differs from that of the histamine H2-receptor antagonists (H2-blockers),
      prostaglandin analogs will, whenever possible, be compared with the H2-blockers
      [cimetidine (Tagamet), ranitidine (Zantac), nizatidine (Axid) and famotidine
      (Pepcid)], currently the cornerstone of peptic ulcer therapy in this country.

PMID- 1976295
TI  - Multiple endocrine adenomatosis type I in pregnancy.
AB  - A 26-year-old woman, gravida 1, para 0, having episodes of confusion, slurred
      speech, and blurred vision in pregnancy was documented to have severe
      hypoglycemia with elevated serum insulin and C-peptide levels. Emergency
      treatment for hypoglycemia was necessary several times during pregnancy. A
      healthy female infant was delivered after oxytocin induction of labor. Post
      partum the patient had numerous episodes of severe hypoglycemia in spite of
      constant intravenous glucose. Computerized tomographic scan of the pancreas
      failed to show a lesion, whereas pancreatic arteriography revealed a 2 cm mass in
      the tail of the pancreas. Partial pancreatectomy was performed 6 days after
      delivery. Microscopic examination of the tissue confirmed the presence of an
      insulinoma. Hypercalcemia developed together with elevated parathyroid hormone
      levels. The presence of an insulinoma, hypercalcemia, and a history of
      hyperparathyroidism in two relatives indicates that this is a case of multiple
      endocrine adenomatosis type I first diagnosed during pregnancy.

PMID- 1976296
TI  - Uterine hyperstimulation after low-dose prostaglandin E2 therapy: tocolytic
      treatment in 181 cases.
AB  - There is limited information about uterine hyperstimulation after low-dose
      prostaglandin E2 therapy. The purpose of this retrospective study was to describe
      our combined experience with this undesired effect by use of three techniques for
      prostaglandin E2 administration. Uterine hyperstimulation was present if the
      contraction frequency was more than five in 10 minutes or if contractions
      exceeded 2 minutes in duration. A total of 181 cases were evaluated during a 51
      month period. The rates of hyperstimulation were 7.3% (167/2297) in the group
      that received intravaginal tablets (3.0 mg), 2.9% (12/408) with intravaginal gel
      (2.5 mg), and 0.5% (2/394) with intracervical gel (0.5 mg). Hyperstimulation
      usually began within the first hour for the group that used gel and within the
      first 4 hours for the tablet group. A beta 2-adrenergic drug (hexoprenaline or
      terbutaline) was infused routinely without adverse effects and with rapid
      resolution of the worrisome findings in 178 (98.3%) cases. The remaining three
      cases required cesarean delivery and had no evidence of neonatal compromise. We
      conclude from this large, combined series that uterine hyperstimulation after low
      dose prostaglandin E2 therapy is uncommon and usually rapidly reversible with
      beta 2-adrenergic therapy without apparent untoward effects.

PMID- 1976297
TI  - Adjusting the loading dose of magnesium sulfate for tocolysis.
AB  - The purpose of this prospective study was to establish a method to calculate a
      loading dose of magnesium sulfate so as to achieve therapeutic levels of
      tocolysis more quickly. Fifty patients in preterm labor were enrolled. In the
      first phase 25 patients were studied so that the apparent volume of distribution
      for the loading dose of magnesium sulfate could be estimated and an adjusted
      loading dose could be calculated. The efficacy of this adjusted loading dose was
      then tested on a further 25 patients in the second phase. We found that the
      apparent volume of distribution could be accurately estimated and an adjusted
      loading dose calculated, with the use of ideal body weight, degree of
      underweight, and current use of beta-sympathomimetics. In the adjusted loading
      dose group therapeutic levels were achieved more often, with higher postloading
      magnesium levels and a greater decrease in contraction index immediately after
      the loading dose. We conclude that an adjusted loading dose can be calculated for
      magnesium sulfate to optimize tocolytic therapy.

PMID- 1976298
TI  - Prolonged benefit in the treatment of chronic idiopathic urticaria with
      astemizole.
AB  - A double-blind clinical trial of 51 patients with chronic idiopathic urticaria
      using oral astemizole for 8 weeks demonstrated significant improvement in
      symptoms and lesions in 75% of treated patients versus 20% in the placebo group.
      The suppression of urticaria persisted for an average of 38 days, demonstrating
      the long duration of action of astemizole.

PMID- 1976299
TI  - Restriction enzyme analysis of mitochondrial DNA of the Aspergillus flavus group:
      A. flavus, A. parasiticus, and A. nomius.
AB  - Mitochondrial DNA restriction fragment length polymorphisms were identified that
      clearly distinguish Aspergillus flavus, A. parasiticus, and A. nomius.
      Mitochondrial DNAs of A. flavus and A. parasiticus were found to be circular, and
      their size was estimated size to be 32 kilobases. A restriction map was
      constructed for the mitochondrial genome of an A. parasiticus isolate by using
      four restriction endonucleases. Four genes tested were found to have the same
      order as in the mitochondrial genome of A. nidulans. The mitochondrial genome of
      A. nomius was estimated to be 33 kilobases.

PMID- 1976300
TI  - Use of nuclear DNA restriction fragment length polymorphisms to analyze the
      diversity of the Aspergillus flavus group: A. flavus, A. parasiticus, and A.
      nomius.
AB  - Recombinant DNA clones carrying high-copy or low-copy sequences from Aspergillus
      nidulans and Neurospora crassa were used to identify restriction fragment length
      polymorphisms (RFLPs) diagnostic for members of the A. flavus group: A. flavus,
      A. parasiticus, and A. nomius. These fungi were resolved into three distinct
      categories when they were grouped according to RFLP patterns. Subgroups within
      these categories were also evident. This limited RFLP analysis of nuclear DNA of
      members of the A. flavus group did not identify any RFLPs that differentiate
      these isolates on the basis of toxin production, but limited correlation with
      geographic location was observed.

PMID- 1976301
TI  - N-methyl-D-aspartate stimulates the release of dopamine from rat hippocampal
      slices.
AB  - Rat hippocampal slices were loaded with [14C]dopamine (DA) and superfused
      continuously with oxygenated Mg2(+)-free Krebs-Henseleit solution. A 5-min pulse
      of 1 mM N-methyl-D-aspartate (NMDA) temporarily enhanced the basal release of DA
      by 30%. This effect was blocked by 50 microM D,L-2-amino-5-phosphonovalerate, a
      selective NMDA receptor antagonist, as well as by 0.5 microM tetrodotoxin. These
      results suggest that NMDA receptors on hippocampal interneurons may modulate the
      DA release. A possible link between the NMDA-induced release of DA and mechanisms
      enabling the maintenance of synaptic long-term potentiation in the hippocampus is
      discussed.

PMID- 1976302
TI  - Study on the mechanism of carbon monoxide induced endothelium-independent
      relaxation in porcine coronary artery and vein.
AB  - In superfusion experiments on isolated porcine coronary arterial and venous ring
      preparations precontracted by prostaglandin F2 alpha repeated bolus application
      of carbon monoxide induced a reproducible relaxation. The vessels were rubbed to
      remove the endothelium, 30 min superfusion with 10(-5) M of 8-bromocyclic-GMP
      decreased the tension in coronary artery and vein and reduced the carbon monoxide
      response in the latter. Methylene blue increased the tone and inhibited the
      carbon monoxide effect in both vessels. The results show that carbon monoxide
      relaxing action on vascular smooth muscle might be due to activation of guanylate
      cyclase similar to the action on nitric oxide and/or endothelium-derived relaxing
      factor.

PMID- 1976303
TI  - Coupling of adenosine A1 receptors to a G-protein in coated vesicles isolated
      from bovine brain: presence of pertussis and cholera toxin substrates.
AB  - Adenosine A1 receptors have been described in coated vesicles isolated from
      bovine brain (Gonzalez-Calero et al., J. Neurochem. 1990, 55, 106-113). Addition
      of non hydrolyzable GTP analogue (guanyl-5-yl-imidodiphosphate) caused a
      transition of the receptor from the high- to the low-affinity state, without any
      significant change in the total binding sites. The presence of G-proteins has
      been investigated by pertussis and cholera toxins catalyzed ADP-ribosylation. A
      band of Mr = 41,000 D, similar to the alpha Gi subunit, was specifically labeled
      in the presence of preactivated pertussis toxin. Bands of Mr = 42,000 D and Mr =
      47,000 D were specifically labeled in the presence of preactivated cholera toxin.
      These results confirm the presence of GTP binding proteins (alpha Gi and alpha
      Gs) in coated vesicles isolated from bovine brain.

PMID- 1976304
TI  - Retroviral-mediated gene transfer of the leukocyte integrin CD18 subunit.
AB  - Children with leukocyte adherence deficiency (LAD) exhibit heterogeneous defects
      in the leukocyte integrin CD18 subunit that prevent surface expression of
      functional CD11/CD18 leukocyte integrin adherence complexes. We used a retroviral
      vector, designated LCD18SN, to transfer the CD18 cDNA into K562 human myeloid
      leukemia cells and into EBV B-cells from a child with LAD. Transfer of the
      LCD18SN retroviral construct, which expresses the CD18 cDNA from the Moloney
      Murine leukemia virus (MoMLV) long terminal repeat (LTR), into K562 cells
      resulted in relatively high levels of CD18 mRNA and intracellular protein.
      Retroviral-mediated gene transfer of CD18 into LAD EBV B-cells resulted in low,
      but readily measurable, levels of surface expression of the CD11a/CD18 complex in
      these previously deficient lymphocytes. The reconstitution of surface expression
      of the CD11a/CD18 complex by gene transfer of the CD18 cDNA into LAD EBV B-cells
      indicates that this syndrome represents a candidate disorder for gene therapy.

PMID- 1976305
TI  - Glutathione and gamma-glutamyl transpeptidase in the adult female rat brain after
      intraventricular injection of LHRH and somatostatin.
AB  - Glutathione content and glutamyl transpeptidase activity in different regions of
      adult female rat brain were determined at 10 and 30 min following
      intraventricular injection of LHRH and somatostatin. Hypothalamic glutathione
      levels were significantly elevated at 10 and 30 min after a single injection of a
      0.1 micrograms dose of LHRH. On the contrary, glutathione levels significantly
      decreased in the hypothalamus, cerebral cortex and cerebellum at 10 and 30 min
      after 0.5 or 1 microgram dose. However, significant decrease in brain stem
      glutathione was evident at 30 min after 0.5 microgram and 10 min after the 1
      microgram dose. Somatostatin at doses of 0.5 microgram and 1 microgram
      significantly decreased glutathione levels in all four brain regions both at 10
      and 30 min following injection into the 3rd ventricle. Gamma-glutamyl
      transpeptidase activity in the hypothalamus and cerebral cortex was significantly
      elevated after intraventricular injection of LHRH. However, a significant
      increase in gamma-glutamyl transpeptidase activity in cerebellum and brain stem
      was seen only with 0.5 and 1 micrograms doses of LHRH. Somatostatin also
      significantly increased gamma-glutamyl transpeptidase activity in hypothalamus,
      cerebral cortex, brain stem and cerebellum. The decrease in glutathione levels
      with corresponding increase in gamma-glutamyl transpeptidase activity after
      intraventricular administration of LHRH and somatostatin suggests a possible
      interaction between glutathione and hypothalamic peptides.

PMID- 1976306
TI  - [Class II HLA typing based on the restriction fragment length polymorphisms of
      DNA].

PMID- 1976307
TI  - The changing epidemiology of leptospirosis in Europe. A report on the 6th meeting
      of European Leptospira workers, Brno, Czechoslovakia, September 1988.

PMID- 1976308
TI  - Medical assistants as drug prescribers.

PMID- 1976309
TI  - ECT and tardive dyskinesia.
AB  - Three cases of elderly depressed patients with symptoms of tardive dyskinesia
      (TD) subsequently treated with electroconvulsive therapy (ECT) are presented.
      These cases are discussed in relation to several cases reported in the literature
      of ECT and TD. The possibility of improvement in symptoms of TD in certain
      patients is discussed.

PMID- 1976310
TI  - Immunobiology of normal and diabetic pregnancy.
AB  - The International Congress of Immunobiology of Normal and Diabetic Pregnancy
      brought together a heterogeneous group of workers to consider one of the most
      fascinating areas of immunology. The meeting, which proved to be a thinkshop as
      much as a workshop, developed along two major lines: (1) an examination of new
      data in normal pregnancy immunology, from both the research and clinical points
      of view and (2) analysis of the suspected problems of diabetic pregnancy.
      'Suspected' because pregnancy-related problems in diabetic women are not due
      solely to metabolic disturbances, but also involve immunological aspects of
      diabetes, particularly where type I diabetes is concerned.

PMID- 1976311
TI  - Class I and class II MHC gene products differentially affect the fate of V beta 5
      bearing thymocytes.
AB  - We have previously shown that T cells bearing V beta 5+ T-cell receptors (TCRs)
      are frequent in B10 (H-2b) and B10.Q (H-2q) mouse strains but are rare in the
      congenic strain B10.BR (H-2k). Furthermore, we have found that V beta 5 bearing T
      cells appear to be excluded from the B10 alloresponse to I-Abm12 despite the
      participation of most other V beta bearing cells. To further study MHC effects on
      V beta 5 expression, we have generated two V beta 5 specific monoclonal
      antibodies and show here that V beta 5 expressing T cells are clonally deleted
      from strains expressing a class II, I-E molecule. Furthermore, I-E- strains
      generate few CD4+ V beta 5+ T cells despite significant numbers of V beta 5+ T
      cells in the CD8+ subset. Thus, V beta 5 bearing T cells are positively selected
      by class I MHC molecules, clonally deleted by class II I-E molecules, and poorly
      selected by class II I-A molecules.

PMID- 1976312
TI  - The etiology of XX sex reversal.
AB  - The primary testis-determining function is exerted by a gene in the sex
      determining region of the human Y chromosome. This gene is termed the sex
      determining factor or TDF. A zinc finger gene, ZFY, residing in this region has
      been cloned and characterized. It is a candidate for TDF. A challenge to future
      molecular research is to clarify the function of a zinc finger gene on the X
      chromosome, ZFX, that shows high structural similarity to ZFY. Furthermore, the
      existence of other genes involved in sex determination is likely but so far
      unproven. Sex reversal leading to testes in apparently XX individuals (XX males)
      is most often due to the presence of TDF on the paternally derived X chromosome.
      The abnormality arises during meiosis in the father when an abnormal exchange
      leads to the transfer onto the X of the entire pseudoautosomal region plus a
      portion of the Y chromosome-specific region including TDF from the Y. An XX male
      resulting from such an exchange is described. 10-20% of XX males do not have Y
      DNA. Two major mechanisms to explain such Y(-) XX males are discussed. First,
      several published pedigrees show clear-cut dominant autosomal or X chromosomal
      inheritance of XX maleness. These patients are always Y(-) and usually have
      sexual ambiguity. This indicates the existence of other genes, obviously
      'downstream' from TDF, that when mutated can trigger testis determination.
      Nothing concrete is presently known about these putative genes, but their
      phenotypic effect is slightly different from that of TDF. Second, mosaicism with
      a prevalent XX lineage and a hidden or scarce lineage containing a Y chromosome
      can explain some apparently Y(-) XX males. Two XX/XXY mosaic patients are
      described in detail. In one, only a combination of DNA hybridization and
      cytogenetic studies led to the discovery of the XXY cell line. In conclusion, XX
      sex reversal in man is caused by at least 3 mechanisms, viz. abnormal Y-X
      interchange, genes other than TDF, and mosaicism.

PMID- 1976313
TI  - [Homeotic genes].
AB  - Homeotic genes occupy a central position in the hierarchy of genes controlling
      the early steps of embryonic development in Drosophila. They are involved in the
      specification of the individual identity of each segment of the insect's body.
      Most homeotic genes of Drosophila are located in two large gene clusters, the
      Antennapedia complex (ANT-C) and the Bithorax complex (BX-C). These genes are
      expressed in two partially overlapping domains whose positions along the anterior
      posterior axis of the organism are colinear with their position within each
      complex. Five genes in the ANT-C are involved in the specification of the
      identity of some segments of the head and of that of the first and second
      thoracic segments. The three genes of the BX-C determine the identities of the
      posterior compartment of the second and third thoracic segments and of the eight
      abdominal segments. Molecular studies have revealed that the proteins coded by
      the homeotic genes share a 60 amino acid motif, the homeo box, whose helix-turn
      helix structure enables them to bind as transcription factors to specific DNA
      sequences in the cis-acting regulatory regions of their target genes. The high
      degree of phylogenetic conservation of the homeobox has made possible the
      identification and the isolation of more than fifty homeobox genes (Hox genes) in
      many eukaryotic organisms including nematode, Xenopus, mouse and man. In the
      mouse and human genomes Hox genes are clustered in tandem in four large gene
      complexes located on separate chromosomes. The relative positions of the genes
      within the clusters and the positions of the anterior boundaries of their
      expression domains along the anterior-posterior axis of the central nervous
      system and prevertebral column of the mouse embryo were found to be colinear. The
      similarities between the structure, organization and pattern of expression of the
      homeotic genes of Drosophila and of the homeobox genes of vertebrates suggest
      that some basic principles of embryonic organization and development have been
      preserved during the long period of evolution that has elapsed since the
      divergence of the phylogenetic lineages leading to vertebrates and arthropods.

PMID- 1976314
TI  - [Changes in blood bilirubin and plasma activity of gamma-glutamyl transferase in
      lambs experimentally infested with Fasciola hepatica].
AB  - F hepatica infection of lambs (single dose of 150 metacercariae) increased the
      plasma gamma-glutamyl transferase (GGT) activity and the total serum bilirubin
      concentration. Thus it might present a risk of inducing yellow fat. It had no
      effect on the plasma carotenoid level.

PMID- 1976315
TI  - [Effect of cimaterol on nitrogen metabolism in fattening bullocks].
AB  - Nitrogen balance was studied in 5 bulls fed a concentrated diet containing 0 or 4
      ppm cimaterol. Cimaterol increased nitrogen retention, mainly by reducing urinary
      nitrogen excretion due to decreased body protein degradation. There was a
      tendency for reduced nitrogen utilization efficiency when treatment was
      prolonged.

PMID- 1976316
TI  - Characterization of the mouse 84-kD heat shock protein gene family.
AB  - The nucleotide sequence of a 6-kb region containing the gene for mouse 84-kD heat
      shock protein, HSP84, was determined. The hsp84 gene codes for a 5,500-base
      transcript and consists of 11 exons and 10 introns, ranging in length from 94 to
      357 bp and 85 to 1,271 bp, respectively. One of the exons codes for a stretch of
      highly charged amino acids with two known phosphorylation sites. The presence of
      numerous introns in the hsp84 gene suggests that synthesis of the HSP84 protein
      would be precluded during severe heat shock, since such conditions interfere with
      splicing. The first intron, which is the largest, is located at the exact
      boundary between the 5'-untranslated region and the coding region and contains a
      sequence homologous to the heat shock element (HSE), an enhancer that is a
      characteristic feature of heat-inducible genes. A 71% homology was found between
      a 569-bp stretch within the first intron of the hsp84 gene, which includes the
      HSE-like sequence, and a portion of the first intron of the previously reported
      sequence of the human hsp89 beta gene. The promoter region of the hsp84 gene
      contained G + C-rich upstream sequences, potential binding sites for
      transcription factor Sp1, and a canonical TATA box. The hsp84 gene family
      includes at least six different hsp84-related pseudogenes, which arose about 2-3
      million years ago.

PMID- 1976317
TI  - Fifteenth congress of the International Union of Crystallography. Bordeaux,
      France, 19-28 July 1990. Abstracts.

PMID- 1976318
TI  - Comparison of 3H-para-aminoclonidine binding to different platelet preparations.
AB  - The binding to human platelets of 3H-para-aminoclonidine (3H-PAC), an alpha2
      adrenoceptor partial agonist, appears to be altered in depressed patients. We
      observed that the parameters of 3H-PAC binding to purified plasma membranes from
      platelets of normal Red Cross volunteers, compare favorably to those reported for
      binding to normal human autopsy prefrontal cortical lysates. However, only
      purified plasma membranes from platelets yielded a close comparison. 3H-PAC
      binding to intact platelets from healthy volunteers was less than 10%
      displaceable by an alpha2 adrenoceptor antagonist and was therefore
      unquantifiable. A low percent of specific binding (approx. 35%) was also observed
      in washed platelet lysates, and the binding was not of very high affinity (KD
      greater than 10 nM). In contrast, the binding of 3H-PAC to platelet purified
      plasma membranes from healthy subjects displayed two high affinity binding sites
      (KD1 = 10.6 pM and KD2 = 1.2 nM). These results are discussed in relation to our
      recent finding of elevated 3H-PAC binding to platelet purified plasma membranes
      from depressed patients as compared to healthy subjects.

PMID- 1976319
TI  - Effects of various direct or indirect dopamine agonists on the latency of the
      acoustic startle response in rats.
AB  - The effects of dopamine agonists were investigated on the latency of the acoustic
      startle response in male Wistar rats. Four indirect dopamine agonist were tested:
      GBR 12783 (5-20 mg/kg), BTCP (5-20 mg/kg), dexamphetamine (3-6 mg/kg) and L-DOPA
      100 mg/kg associated with benserazide 25 mg/kg; they induced an increase in
      startle latency. Apomorphine at a dose (50 micrograms/kg) known to decrease
      dopaminergic transmissions, was ineffective on the startle response. On the
      contrary, at 0.6 or 2 mg/kg, apomorphine induced an increase in the startle
      latency. A similar effect was observed with bromocriptine at 10 mg/kg from the
      10th min up to at least the 9th hour after treatment. The specific agonist of D2
      receptors Ru 24926 (0.45 mg/kg) enhanced the startle latency as well as the
      specific agonist of D1 receptors SKF 38393 (10 mg/kg). The association of these
      drugs resulted in an apparent additivity of their individual effects. The effect
      of apomorphine (0.6 mg/kg) was only partially reduced by a high dose of the
      specific D2 antagonist amisulpride (80 mg/kg) and more clearly antagonized by the
      specific D1 antagonist SCH 23390 (50 micrograms/kg). It is concluded that D2 and
      D1 receptors contribute to the increase in startle latency elicited by direct or
      indirect dopamine agonists.

PMID- 1976320
TI  - Activation of protein kinase C by presynaptic FLRFamide receptors facilitates
      transmitter release at an aplysia cholinergic synapse.
AB  - Modulation of evoked quantal transmitter release by protein kinase C (PKC) was
      investigated at an identified cholinergic neuro-neuronal synapse of the Aplysia
      buccal ganglion. Evoked acetylcholine release was increased by a diacylglycerol
      analog that activates PKC and was decreased by H-7, a blocker of PKC. FLRFamide
      facilitated evoked quantal release by increasing presynaptic Ca2+ influx. The
      inhibition of PKC by H-7 prevented both the increase of presynaptic Ca2+ influx
      and the facilitation of evoked acetylcholine release induced by the activation of
      presynaptic FLRFamide receptors. These results provide evidence that the
      activation of PKC could be a step in the intracellular pathway by which FLRFamide
      receptors increase evoked quantal acetylcholine release.

PMID- 1976321
TI  - Facilitatory and inhibitory transmitters modulate calcium influx during action
      potentials in aplysia sensory neurons.
AB  - Serotonin (5-HT) produces presynaptic facilitation and FMRFamide produces
      presynaptic inhibition in Aplysia sensory neurons. These effects may involve the
      modulation of Ca2+ influx into sensory neuron terminals during action potentials.
      Here, we have used the Ca2+ indicator dye fura-2 to monitor directly the effects
      of 5-HT and FMRFamide on internal Ca2+ concentration ([Ca2+]i). 5-HT caused a 50%
      increase in the transient rise in [Ca2+]i in response to action potentials,
      whereas FMRFamide decreased the [Ca2+]i transient by 40%. Neither transmitter
      altered the resting [Ca2+]i, the time course of recovery of the [Ca2+]i
      transient, or the [Ca2+]i transients produced by intracellular injection of CaCl2
      or inositol 1,4,5-trisphosphate. We conclude that the effects of the transmitters
      on the action potential-induced [Ca2+]i transient are due to changes in Ca2+
      influx and not in intracellular Ca2+ homeostasis.

PMID- 1976322
TI  - Alterations of blood analyses at relapse of osteosarcoma and Ewing's sarcoma.
AB  - Alterations of blood analyses have been studied at relapse of patients with
      osteosarcoma and Ewing's sarcoma. The tests included erythrocyte sedimentation
      rate (ESR), haemoglobin (Hb), leukocyte and thrombocyte counts, gamma
      glutamyltransferase (GT), lactate dehydrogenase (LD) and alkaline phosphatase
      (ALP). Sixteen relapsing patients diagnosed from 1970 to 1987 were eligible in
      each sarcoma group. Median age was 16 years (range 9-30) at diagnosis. The blood
      tests seemed to be of no help in detecting relapse of osteosarcoma, while ESR, LD
      and GT rose significantly in relapsing patients with Ewing's sarcoma. ESR was
      best correlated to disease activity.

PMID- 1976323
TI  - Magnetic resonance imaging of the foot and ankle.

PMID- 1976324
TI  - Ipratropium bromide: an additive effect?

PMID- 1976325
TI  - Differentiation between extrahepatic and intrahepatic cholestasis by discriminant
      analysis.
AB  - Discriminant analysis was used to differentiate between extrahepatic biliary
      atresia and intrahepatic cholestasis. Among the ten laboratory variables tested,
      three (gamma-glutamyl transpeptidase, alkaline phosphatase and total serum
      bilirubin) were useful in the differential diagnosis. gamma-Glutamyl
      transpeptidase contributed most to the discrimination (85%). From a population
      study of 28 babies with extrahepatic biliary atresia and 24 infants with
      intrahepatic cholestasis, the procedure achieved a diagnostic accuracy and
      specificity of 92.9% and an efficiency of 92.3%. The jackknife procedure has also
      confirmed that the mathematical model was robust for discriminant analysis and
      therefore it may be valid for screening infants with cholestasis for early
      surgical intervention. Discriminant analysis is a useful adjunct for
      differentiation between intrahepatic cholestasis and extrahepatic biliary
      atresia.

PMID- 1976326
TI  - The treatment of cytostatic drug-induced emesis. Proceedings of an official
      satellite symposium to the 5th European Conference on Clinical Oncology (ECCO5).
      London, September 1989.

PMID- 1976327
TI  - The adrenergic receptors.

PMID- 1976328
TI  - Hormonal regulation of phosphatidylcholine breakdown.

PMID- 1976329
TI  - Role of Ca2+/calmodulin-dependent protein phosphorylation in signal transduction.

PMID- 1976330
TI  - Phosphatidylinositol kinase and cell transformation.

PMID- 1976331
TI  - Specific associations between tubulin and G proteins: participation of
      cytoskeletal elements in cellular signal transduction.

PMID- 1976332
TI  - Involvement of the gamma subtype of protein kinase C in GABA release from the
      cerebellum.

PMID- 1976333
TI  - Differences in receptor crosstalk in cultured cells versus established cell line
      of vascular smooth muscle.

PMID- 1976334
TI  - EDRF is an intracellular second messenger and autacoid to regulate cyclic GMP
      synthesis in many cells.

PMID- 1976335
TI  - Direct and indirect regulation of cardiac L-type calcium channels by beta
      adrenoreceptor agonists.

PMID- 1976336
TI  - EDRF-formation increases cGMP-levels in cultured endothelial cells.

PMID- 1976337
TI  - Pertussis toxin-sensitive G-proteins: participation in the modulation of voltage
      dependent Ca2+ channels by hormones and neurotransmitters.

PMID- 1976338
TI  - Gentamicin nephropathy and contrast media. A comparison between diatrizoate and
      iohexol in rats.
AB  - Urine profiles were followed for 3 or 9 days after intravenous injection of
      diatrizoate, iohexol or saline in 30 rats, where a tubulo-interstitial
      nephropathy was induced by gentamicin given over a 14-day period. Another 10 rats
      who had an injection of saline served as controls. Iohexol increased the
      excretion of lactate dehydrogenase significantly more than both saline and
      diatrizoate for the first 3 days, whereas diatrizoate had no effect. Both media
      caused significantly increased excretion of L-gamma-glutamyltransferase compared
      with saline, but iohexol significantly more than diatrizoate. Compared with
      saline S-creatinine was significantly increased following iohexol at 24 h, 3 and
      9 days, and following diatrizoate only at 9 days. Among rats having gentamicin
      light microscopy revealed more severe changes in kidneys exposed to iohexol than
      to either diatrizoate or saline 3 days after their injection. Six days later no
      obvious differences were found between the 3 groups. In conclusion, iohexol
      induced more renal dysfunction than diatrizoate in this animal model of
      gentamicin induced nephropathy.

PMID- 1976339
TI  - Ischaemic left ventricular failure: evidence of sustained benefit after 18
      months' treatment with xamoterol.
AB  - The long term effects of treatment with xamoterol in 14 patients aged 44-73 with
      mild to moderate heart failure as a result of ischaemic heart disease are
      reported. After 18 months' treatment with xamoterol, patients were assessed in a
      randomised double blind crossover comparison of xamoterol (200 mg twice a day)
      and placebo, each given for one month. Compared with placebo, xamoterol
      significantly increased exercise duration and work done on a bicycle ergometer
      and reduced the maximum exercise heart rate. Assessment of symptoms and
      activities at 12 months by visual analogue and Likert scales showed a trend
      towards the relief of symptoms of breathlessness and tiredness and an improvement
      in activity. There was an improvement in the clinical signs of heart failure and
      no haemodynamic deterioration over a 12 month period as assessed by ejection
      fraction. The improvement in exercise tolerance, symptoms, and activities was
      sustained for 18 months without side effects or development of tolerance.

PMID- 1976340
TI  - Outpatient medical management of postpartum psychiatric disorders.
AB  - Many psychiatric treatment modalities may be used in treating postpartum
      psychiatric disorders. A structured psychiatric interview specifically designed
      to elicit symptoms of postpartum depression and psychosis can be very useful in
      diagnosing the type and severity of the disorder. Once the diagnosis has been
      made, a combination of education, individual and group psychotherapy, and
      psychopharmacologic interventions can relieve the symptoms and help restore the
      new mother to her previous level of functioning.

PMID- 1976341
TI  - The solvents cremophor EL and Tween 80 modulate daunorubicin resistance in the
      multidrug resistant Ehrlich ascites tumor.
AB  - Cremophor EL (polyoxyethylene castor oil) and Tween 80, used as solvents for
      cyclosporin A and VP-16, respectively, were found to reverse the multidrug
      resistant (MDR) phenotype. In daunorubicin (DNR) resistant Ehrlich ascites tumor
      cells (EHR2/DNR+), both solvents at percentages of 0.01% (v/v) enhanced DNR
      accumulation to sensitive levels. Cremophor EL and Tween 80 did not influence DNR
      accumulation in drug-sensitive cells (EHR2). The concentration of cyclosporin A
      alone that enhanced DNR accumulation in EHR2/DNR+ cells to sensitive levels was 5
      micrograms/mL whereas 0.2 micrograms/mL of cyclosporin A dissolved in 0.001%
      (v/v) Cremophor EL enhanced DNR accumulation to sensitive levels, thus indicating
      synergy between Cremophor EL and cyclosporin A. Cyclosporin A had a negligible
      effect on DNR accumulation in the drug-sensitive cells. In clonogenic assays, the
      LD10 of DNR was 1 microM in EHR2/DNR+ cells. Combining 1 microM DNR with non
      toxic amounts of Cremophor EL (0.001% and 0.002%, v/v) potentiated the
      cytotoxicity of DNR and resulted in a cell kill of 77% and 86%, respectively, in
      the resistant cells. In non-toxic amounts, CrEL and Tween 80 acted
      synergistically with reduced concentrations of verapamil, resulting in DNR
      accumulation approaching close to the sensitive level. Azidopine photoaffinity
      labeling of P-glycoprotein in plasma membrane vesicles from EHR2/DNR+ cells was
      inhibited 100% and 80%, by 0.003% (v/v) Cremophor EL or Tween 80, respectively.
      These data permit the conclusion that non-toxic amounts of CrEL and Tween 80
      modulated DNR resistance by raising intracellular DNR levels, due to their
      abilities to bind to the plasma membrane P-glycoprotein.

PMID- 1976344
TI  - Bone marrow transplantation.

PMID- 1976343
TI  - Terfenadine, a potent histamine H1-receptor antagonist in the treatment of grass
      pollen sensitive asthma.
AB  - 1. We have assessed the effect of a specific histamine H1-receptor antagonist,
      terfenadine, in the treatment of atopic asthmatics during the grass pollen
      season. 2. Eighteen mild, grass pollen sensitive asthmatics (10F, 8M, mean +/-
      s.e. mean age 34.7 +/- 5.6 years), all of whom were controlled on inhaled beta 2
      adrenoceptor agonists alone, took part in a 9 week, double-blind, crossover study
      using terfenadine 180 mg three times daily and placebo. Throughout the study
      patients recorded peak expiratory flow rate (PEFR) twice daily, symptoms of
      cough, wheeze, breathlessness and chest tightness (scored 0-3), and their use of
      bronchodilators. Methacholine inhalation challenge tests were performed each
      week. Data were analysed by a method suitable for a two group, two period
      crossover trial with baseline measurements. 3. Terfenadine significantly reduced
      symptoms of cough by 76.9% (P less than 0.05) and wheeze by 46.9% (P less than
      0.02). Symptoms of breathlessness and chest tightness were reduced by 16.8 and
      30.3% respectively but these were not statistically significant. Morning and
      evening PEFR rose by 5.5 (P less than 0.001) and 6.2% (P less than 0.003)
      respectively on treatment with terfenadine and bronchodilator use fell by 40.3%.
      A progressive increase in methacholine sensitivity was seen in both treatment
      groups throughout the study but did not reach statistical significance. 4. We
      conclude that treatment with terfenadine during the grass pollen season in
      sensitive asthmatics reduced their symptoms and bronchodilator requirements and
      produced a modest improvement in their lung function without affecting the
      development of increased methacholine sensitivity that occurred during the grass
      pollen season.

PMID- 1976345
TI  - Bone marrow transplantation: introduction and overview.

PMID- 1976346
TI  - Cytomegalovirus infection and interstitial pneumonia after bone marrow
      transplantation.

PMID- 1976347
TI  - Selection of marrow donors for patients lacking an HLA-identical sibling.

PMID- 1976342
TI  - Beta-adrenoceptor partial agonists: a renaissance in cardiovascular therapy?

PMID- 1976348
TI  - Therapeutic use of hematopoietic growth factors in bone marrow transplantation.

PMID- 1976349
TI  - Bone marrow transplantation for immunodeficiency and genetic diseases.

PMID- 1976350
TI  - Bone marrow transplantation for aplastic anemia: recent advances and comparisons
      with alternative therapies.

PMID- 1976351
TI  - Bone marrow transplantation for acute nonlymphocytic leukemia (ANL).
AB  - When a patient less than age 55 presents with ANL, it can be recommended that the
      patient and his family be HLA typed prior to initial induction chemotherapy. The
      information gained may be of help for platelet support but, more importantly, if
      the patient fails to achieve a remission, transplantation can be carried out
      straight away. If the patient achieves a first complete remission, the
      therapeutic approach depends upon whether a donor is found. If either a matched
      or one-antigen mismatched family member is identified, transplant in first
      remission or first relapse can be recommended. If no match is found, autologous
      marrow should be stored and a search for an unrelated donor be initiated.
      Currently, we generally restrict the use of autologous marrow or an unrelated
      donor to patients who have suffered an initial relapse, unless in the context of
      a specific clinical protocol. Which of the two approaches, autologous versus
      unrelated, is superior remains unknown.

PMID- 1976353
TI  - Therapy of chronic myelogenous leukemia with bone marrow transplantation.

PMID- 1976352
TI  - Bone marrow transplantation in acute lymphoblastic leukemia.

PMID- 1976354
TI  - Bone marrow transplantation for Hodgkin's disease, non-Hodgkin's lymphoma and
      multiple myeloma.

PMID- 1976355
TI  - Recapitulation of immune ontogeny: a vital component for the success of bone
      marrow transplantation.

PMID- 1976356
TI  - Bone marrow transplantation for solid tumors in pediatrics.

PMID- 1976357
TI  - Role of bone marrow transplantation as treatment for victims of nuclear
      accidents.

PMID- 1976358
TI  - Acute graft-versus-host disease.

PMID- 1976359
TI  - Chronic graft-versus-host disease.

PMID- 1976360
TI  - Engraftment of T-cell-depleted bone marrow in murine models for allogeneic bone
      marrow transplantation.

PMID- 1976361
TI  - T-cell depletion for bone marrow transplantation: effects on graft rejection,
      graft-versus-host disease, graft-versus-leukemia, and survival.
AB  - T-cell depletion of the donor bone marrow offers the most effective approach yet
      reported to prevent graft-versus-host disease and its associated mortality. This
      approach has allowed histoincompatible bone marrow transplants for children with
      immunodeficiency states. It has been more difficult to apply T-cell depletion to
      bone marrow transplants for leukemia. Failure of engraftment and leukemia relapse
      are more frequent than with transplants of unmodified bone marrow. Hopefully more
      effective immunosuppressive and antileukemic preparative regimens can be
      developed to allow successful application of T-cell-depleted transplants and
      effective prevention of graft-versus-host disease.

PMID- 1976362
TI  - Mechanisms for vocal communication following total laryngectomy.

PMID- 1976364
TI  - Evaluation and medical management of thyroid cancer.

PMID- 1976363
TI  - Neck dissection: morbidity and rehabilitation.

PMID- 1976365
TI  - Chemotherapy of patients with recurrent head and neck cancer.

PMID- 1976366
TI  - Combined chemotherapy and radiation for unresectable head and neck cancer.

PMID- 1976367
TI  - The role of induction chemotherapy for organ preservation in laryngeal carcinoma.

PMID- 1976368
TI  - Methodology and clinical applications of cellular DNA content parameters
      determined by flow cytometry in squamous cell cancers of the head and neck.

PMID- 1976369
TI  - Head and neck tumor immunology. II. Humoral immunity.

PMID- 1976371
TI  - Carcinomas of the head and neck.

PMID- 1976370
TI  - Etiologic considerations for head and neck squamous cancers.

PMID- 1976372
TI  - Magnetic resonance imaging of head and neck cancer.

PMID- 1976373
TI  - Diagnostic imaging in the diagnosis of malignant invasion of the carotid artery:
      ultrasound, computed tomography, magnetic resonance imaging.

PMID- 1976374
TI  - Craniofacial resection for tumors of the ethmoid and superior nasal vault.

PMID- 1976375
TI  - Surgical resection for recurrent nasopharynx cancer.

PMID- 1976376
TI  - Advanced basal and squamous cell carcinomas of the skin of the head and neck.

PMID- 1976377
TI  - Interstitial hyperthermia in head and neck oncology.

PMID- 1976378
TI  - Photodynamic therapy in the management of head and neck cancer.

PMID- 1976380
TI  - Autologous rescue with blood-derived stem cells in a child with non-Hodgkin's
      lymphoma.
AB  - Autologous blood-derived stem cells were used for stem-cell rescue in a 5-year
      old boy with chemotherapy-resistant B-Non-Hodgkin's lymphoma (B-NHL) involving
      bone marrow. The high dose chemoradiotherapy was carried out 5 months after
      initial diagnosis during partial remission. The preparative regimen consisted of
      12 Gy fractionated, total-body irradiation (FTBI) before 60 mg/kg etoposide.
      There were 22.96 X 10(4)/kg body weight myeloid precursor cells, granulocyte
      macrophage committed stem cells (CFU-GM) collected by intermittent blood flow
      separation with a Haemonetics 30R in two cytaphereses and stored in liquid
      nitrogen. Also 11, 82 X 10(4) CFU-GM/kg body weight were recovered and transfused
      after thawing. Rapid hematopoietic reconstitution ensued: Erythroid precursors
      were detected on day 9, 1 X 10(9)/L leucocytes were counted on day 11, and 0.5 X
      10(9)/L granulocytes on day 13, respectively. The patient required 3 single-donor
      platelet transfusions, the last one on day 10. On day 17, 100 X 10(9)/L platelets
      were reached. A bone marrow aspirate on the same day showed good trilineage
      regeneration. The patient remained in complete remission 7 months after
      autografting with a normal stem cell content of the bone marrow and in the
      peripheral blood. On day 226, after stem cell infusion, a bone marrow relapse
      occurred.

PMID- 1976379
TI  - Treatment of seasonal allergic rhinitis: a comparison of a combination tablet of
      terfenadine and pseudoephedrine with the individual ingredients.
AB  - This single-centre, double-blind, parallel randomised study of one week's
      duration compared terfenadine 40 mg, pseudoephedrine 60 mg and a combination of
      the two (40 mg/60 mg) given three times a day in the management of hayfever. Of
      88 known hayfever sufferers recruited during the 1988 season 86 were evaluable
      for efficacy. Demographic data were similar, but some significant differences in
      baseline symptom values made direct comparison of post-treatment scores difficult
      to interpret. Nevertheless, comparisons of improvements from baseline show that
      all three treatments provide good control of the individual seven symptoms (nasal
      block, sneezing, runny nose, itchy nose, watery eyes, red eyes, itchy eyes).
      Terfenadine provided a statistically greater improvement in mean total symptom
      score than pseudoephedrine alone. Overall assessments favoured terfenadine and
      the combination, and rhinoscopy examination showed a trend in favour of
      terfenadine alone. Adverse events were recorded more frequently in the
      combination group: 45% of patients versus 21% in the terfenadine group and 26% in
      the pseudoephedrine group. In this group of patients, terfenadine,
      pseudoephedrine or a combination provide good relief of hayfever symptoms,
      including nasal block, with terfenadine and the combination being preferred to
      pseudoephedrine in the treatment of this condition. However, the combination can
      be expected to cause a greater incidence of side-effects.

PMID- 1976381
TI  - Human breast cancer: identification of populations with a high risk of early
      relapse in relation to both oestrogen receptor status and c-erbB-2
      overexpression.
AB  - We recently defined a new early prognostic factor, the ER+(R) status, which
      permits the discrimination of a group presenting a high risk of early relapse
      among the ER+ patients. This group was referred to as ER+(R2) in contrast to
      ER+(R1) which corresponded to the group of ER+ patients having a lower risk of
      early relapse. Taking into account the whole population including the ER- and
      inflammatory tumours, we have extended this view and showed that ER+(R) status is
      a significant predictor of disease-free survival. Determination of c-erbB-2 mRNA
      levels in the same series of tumours showed that high expression of c-erbB-2 mRNA
      is significantly correlated with ER-, inflammatory tumours and with lymph nodes
      involvement. Moreover, a multivariate analysis showed that c-erbB-2 mRNA
      overexpression was a significant predictor of early relapse (P = 0.02), as
      significant as ER negativity and ER+(R2). For ER+ patients a high level of c-erbB
      2 mRNA constitutes a higher risk of relapse for both ER+(R1) and ER+(R2)
      patients. However, in the case of ER- patients, early relapses were strongly
      correlated with c-erbB-2 overexpression. The counterpart of this observation is
      that ER- patients with no overexpression of c-erbB-2 constitute a group with a
      relatively good prognosis.

PMID- 1976383
TI  - A shared internal threonine-glutamic acid-threonine-proline repeat defines a
      family of Dictyostelium discoideum spore germination specific proteins.
AB  - A cDNA denoted pRK270 hybridizes to two mRNA species in RNA blots. The mRNAs
      specific to this clone are not expressed during vegetative growth and
      multicellular development. They are, however, found predominantly during early
      stages of spore germination, suggesting that their synthesis is rapidly and
      coordinately turned on during germination. Two different cDNAs named 270-6 and
      270-11 were isolated, representing the two mRNAs. DNA blot analysis shows that
      270 is a multigene family. Four genes were isolated from Dictyostelium genomic
      libraries and sequenced. The putative proteins coded for by these genes are about
      51,000, 55,000, 76,000, and 100,000 Da. Two of the genes are expressed during
      spore germination while transcripts for the other two are not present during
      spore germination, vegetative growth, or the stages of multicellular development
      studied. The cDNAs and genes code for deduced proteins that possess a very
      unusual internal amino acid repeat comprised of the tetrapeptide threonine
      glutamic acid-threonine-proline. The other portions of the proteins have no
      homology among themselves. The 270-6 protein shows excellent identity with
      avocado (Persea americana) cellulase, indicating that it may function as an endo
      (1,4)-beta-D-glucanase.

PMID- 1976382
TI  - Pyrimidine biosynthesis in parasitic protozoa: purification of a monofunctional
      dihydroorotase from Plasmodium berghei and Crithidia fasciculata.
AB  - Dihydroorotase (DHOase) catalyzes the reversible cyclization of N-carbamoyl-L
      aspartate (L-CA) to L-5,6-dihydroorotate (L-DHO), which is the third enzyme in de
      novo pyrimidine biosynthesis. The enzyme was purified from two parasitic
      protozoa, Crithidia fasciculata (about 16,000-fold) and Plasmodium berghei (about
      790-fold). The C. fasciculata enzyme had a native molecular weight (Mr) of 42,000
      +/- 5000, determined by gel filtration chromatography, and showed a single
      detectable protein band on sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE) with Mr 44,000 +/- 3000. The DHOase from P. berghei
      had a native molecular weight of 40,000 +/- 4000 and a subunit molecular weight
      on SDS-PAGE of 38,000 +/- 3000. The DHOase from both parasites, in contrast to
      the mammalian enzyme which resides on a trifunctional protein of the first two
      enzymes of the pathway, carbamoyl-phosphate synthase and aspartate
      transcarbamylase, is monomeric and has no oligomeric structure as studied by
      chemical cross-linking with dimethyl suberimidate. The rate of cyclization of L
      CA by the C. fasciculata enzyme was relatively high at acidic pH, decreasing to a
      very low rate at alkaline pH. In contrast, the rate of ring cleavage of L-DHO was
      very low at acidic pH and increased to a higher rate at alkaline pH. These pH
      activity profiles gave an intersection at pH 6.6. The Km and kcat for L-CA were
      0.846 +/- 0.017 mM and 39.2 +/- 6.4 min-1, respectively; for L-DHO, they were
      25.85 +/- 2.67 microM and 258.6 +/- 28.5 min-1.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1976384
TI  - Periplasmic metabolism of glutamate and aspartate by intact Bradyrhizobium
      japonicum bacteroids.
AB  - In studies on the uptake and metabolism of [14C]glutamate by Bradyrhizobium
      japonicum bacteroids we found that, in the presence of unlabeled malate,
      succinate or alpha-ketoglutarate, substantial label was recovered in alpha
      ketoglutarate in the reaction mixtures. As much as 30% of the total 14C supplied
      could be found in alpha-ketoglutarate in the reaction mixtures after 30 min and
      this occurred in the absence of detectable labeling of alpha-ketoglutarate in the
      cells. The labeling of alpha-ketoglutarate was almost completely inhibited by
      aminooxyacetate (aminotransferase inhibitor). Direct assay of aspartate
      aminotransferase in intact bacteroids was possible in the presence of very dilute
      Triton X-100 (less than or equal to 0.02%, w/v). The response of the
      aminotransferase to detergent was similar to the response of phosphodiesterase, a
      periplasmic marker, and different from malate dehydrogenase and beta
      hydroxybutyrate dehydrogenase, cytoplasmic markers. Comparison of maximum enzyme
      activity assayable with intact bacteroids and maximum activity in sonicated
      bacteroids indicated that about half of the total cellular aminotransferase
      activity was accessible to the external medium. The combined labeling and enzyme
      assay results indicated that B. japonicum bacteroids have a capability for
      transamination in the periplasmic space. Although this may not be important in
      the transfer of reducing equivalents from host cytoplasm to bacteroids in
      nodules, the transamination capability may facilitate the acquisition of
      metabolites by free-living bacteria.

PMID- 1976385
TI  - Regulation of mammalian melanogenesis. II: The role of metal cations.
AB  - Melanogenesis can be divided into two phases. The first one involves two
      tyrosinase-catalyzed oxidations from tyrosine to dopaquinone and a very fast
      chemical step leading to dopachrome. The second phase, from dopachrome to
      melanin, can proceed spontaneously through several incompletely known reactions.
      However, some metal transition ions and protein factors different from tyrosinase
      might regulate the reaction rate and determine the structure and relative
      concentrations of the intermediates. The study of the effects of some divalent
      metal ions (Zn, Cu, Ni and Co) on some steps of the melanogenesis pathway has
      been approached using different radiolabeled substrates. Zn(II) inhibited
      tyrosine hydroxylation whereas Ni(II) and Co(II) were activators. Ni(II), Cu(II)
      and Co(II) accelerated chemical reactions from dopachrome but inhibited its
      decarboxylation. Dopachrome tautomerase also decreased decarboxylation. When
      metal ions and this enzyme act together, the inhibition of decarboxylation was
      greater than that produced by each agent separately, but amount of carboxylated
      units incorporated to the melanin was not higher than the amount incorporated in
      the presence of only cations. The amount of total melanin formed from tyrosine
      was increased by the presence of both agents. The action of Zn(II) was different
      from other ions also in the second phase of melanogenesis, and its effect on
      decarboxylation was less pronounced. Since tyrosine hydroxylation is the rate
      limiting step in melanogenesis, Zn(II) inhibited the pathway. This ion seems to
      be the most abundant cation in mammalian melanocytes. Therefore, under
      physiological conditions, the regulatory role of metal ions and dopachrome
      tautomerase does not seem to be mutually exclusive, but rather complementary.

PMID- 1976387
TI  - [Substrate specificity of acetyl-CoA-carboxylase from the rat liver].
AB  - The interaction between acetyl-CoA fragments and rat liver acetyl-CoA carboxylase
      was studied. It was found that the 3'-phosphate group did not interfere with the
      enzyme interaction since the substrate properties of acetyl-dephospho-CoA and
      acetyl-CoA are nearly identical. The non-nucleotide substrate analogs S-acetyl
      pantethin and its 4'-phosphate) also displayed substrate properties (V = 1.5% and
      15% of the V for acetyl-CoA carboxylation respectively). The nucleotide fragment
      of the acetyl-CoA molecule produced an appreciable effect on the thermodynamics
      of this substrate interaction with the enzyme. Its physiological role consists in
      all probability, in the activation and propes orientation of the acetyl group in
      the enzyme active center. The far more pronounced substrate properties of S
      acetyl pantethin 4'-phosphate and the inhibitory properties of pantethin 4'
      phosphate (compared to non-phosphorylated analogs) suggest the essential role of
      the beta-phosphate residue of ADP in the acetyl-CoA binding to the enzyme. The
      data obtained suggest also that the hydrophobic region responsible for the acyl
      radical binding, has a site which specifically recognizes the beta-mercaptoethyl
      residue of the CoA pantethin fragment. The pivotal role in the acetyl-CoA
      carboxylase interaction with the substrate is ascribed to the productive binding
      of the acetyl radical; the contribution of individual fragment of the CoA
      molecule is variable.

PMID- 1976386
TI  - Isolation and characterization of the structural gene encoding elongation factor
      3.
AB  - The unique yeast translational factor EF-3 participates in the elongation cycle
      by stimulating the function of EF-1 alpha in binding aminoacyl-tRNA to the
      ribosome. We have isolated the structural gene encoding EF-3 from the yeast
      Saccharomyces cerevisiae. The YEF3 gene is found in one copy per haploid genome
      and is essential for vegetative growth. DNA sequence analysis reveals that the
      YEF3 gene contains an open reading frame of 1044 codons. The deduced amino acid
      sequence has two repeats of a nucleotide-binding motif. Each of these repeats
      shows similarity to the nucleotide-binding motif of hydrophilic, membrane
      associated ATPases including human multidrug resistant protein MDR. Factor 3
      manifests ribosome-dependent ATP hydrolysis. Introduction of the YEF3 gene on a
      high copy number plasmid into yeast strains increases the ribosome-dependent
      ATPase activity and EF-3 protein levels by 3-5-fold. Yeast strains containing
      elevated EF-3 protein levels also exhibit increased sensitivity to the
      aminoglycoside antibiotics hygromycin and paromomycin. These drugs are known to
      increase translational errors. These observations suggest that EF-3 may affect
      translational accuracy.

PMID- 1976388
TI  - [The regulation of the Na, K-ATPase system by neurotransmitters].
AB  - Factors regulating the activity of synaptosomal Na, K-ATPase have been found in
      the cytosol of nerve endings. The activatory effect of the factor increases in
      the presence of neurotransmitters regardless of their direct action on Na, K
      ATPase. Synaptosomal Na, K-ATPase is not sensitive to the factor obtained from
      the cytosol of kidney tissue, or the cytosolic fraction obtained after
      sedimentation of microsomes. The effect of inhibiting low molecular ET(S)
      fraction on Na, K-ATPase activity is not mediated through noradrenaline, dopamine
      and serotonin as well by the system of secondary messengers. Factor stimulated by
      neurotransmitters activates the Na, K-ATPase system affecting the phosphorylating
      intermediates of the enzyme and putting the Na, K-ATPase system in the mode of
      simultaneous transport of Na and K ions.

PMID- 1976389
TI  - [The role of carrier ATPases and neuromediators in neurological disorders].
AB  - Physiological and biochemical processes which take place in the nervous system at
      stroke and neurotrauma are reviewed, and the experience of using low doses of
      steroid derivatives with piridamole in the treatment of central nervous system
      (CNS) disorders is summarized. ATPases (including Na,K-ATPase) are reported to
      play an important role in CNS functioning, the correlation between Na,K-ATPase
      activity and the extent of CNS injury is revealed. The use of NMR-spectroscopy
      method for investigation of brain and spinal cord condition in vivo is suggested.

PMID- 1976390
TI  - [The identification and characteristics of subpopulations of alpha 1-adrenergic
      receptors].
AB  - Rat liver and brain alpha 1-adrenergic receptors were purified 500 fold by
      successive chromatographic steps using heparin- and wheat germ agglutinin
      agarose; an affinity matrix constructed by coupling CP85.224 (a derivative of
      prazosin) to affigel 102. It is shown that the existence in brain of an alpha 1
      adrenergic receptor subpopulation, which is structurally distinct from that
      previously characterized. Chlorethylclonidine, irreversibly inactivates [3H]
      prazosin binding sites in partially purified membrane preparations of rat liver.
      Under identical conditions, only 50% of receptors are irreversibly inactivated.
      Computer modelling of data obtained from the competition by the alpha
      antagonists, WB 4101 and phentolamine, for [3H] prazosin binding to partially
      purified preparations of rat liver is best fit by assuming a single low-affinity
      site for both ligands. However, the partially purified brain preparations
      indicates the presence of two affinity binding sites for these antagonists. Prior
      alkylation of brain receptors with chlorethylclonydyne results in the loss of the
      low-affinity phentolamine and WB4101 binding sites. These data provide evidence
      for the existence of a single receptor subpopulation (alpha 1b) in rat liver and
      for two subpopulations (alpha 1a and alpha 1b) in rat brain. The significance of
      these results in understanding the signal mechanisms which allow cellular
      responsiveness to alpha 1-adrenergic receptor agonists is discussed.

PMID- 1976391
TI  - Transmission of HTLV-I by blood transfusion and its prevention by passive
      immunization in rabbits.
AB  - To determine the minimum volume of blood required to transmit human T-cell
      leukemia virus type I (HTLV-I), heparinized blood was collected from a virus
      infected female rabbit and aliquots of 10, 5, 1, 0.5, 0.1, and 0.01 mL were
      transfused into groups of two male rabbits each. All 10 rabbits transfused with
      10 to 0.1 mL and 1 of 2 rabbits transfused with 0.01 mL seroconverted for HTLV-I
      after 2 to 4 weeks. HTLV-I-producing lymphoid cell lines of recipient origin were
      established from one seroconverted rabbit of each aliquot group. To determine the
      ability of passive immunization to protect against HTLV-I infection, two groups
      of three rabbits were first transfused with 5 mL of blood from the same virus
      infected rabbit and then infused after 24 or 48 hours with 10 mL of HTLV-I immune
      globulin (77 mg/mL of IgG) prepared from seropositive healthy persons. None of
      the 24-hour immunization group seroconverted for HTLV-I during the observation
      period of six months; however, all of the 48-hour immunization group became
      seropositive after 2 to 4 weeks. These results indicate that HTLV-I can be
      transmitted with as little as 0.01 mL of virus-infected blood, and that passive
      immunization is effective in preventing cell-to-cell infection of HTLV-I when
      given within 24 hours of transfusion of virus-infected blood.

PMID- 1976393
TI  - Annual congress of the German and Austrian Society of Hematology and Oncology.
      Cologne, September 30-October 3, 1990. Abstracts.

PMID- 1976394
TI  - Mutational activation of the c-K-ras gene in human pancreatic carcinoma.
AB  - We have reported the presence of c-K-ras oncogenes activated by single point
      mutations at codon 12 in a vast majority of human pancreatic carcinomas. Formalin
      fixed, paraffin-embedded specimens from surgical resections, autopsies and
      biopsies were used as well as snap frozen surgical specimens. The high oncogene
      incidence has been confirmed in other studies and indicate that somatic
      mutational activation of the c-K-ras gene is an important event in the
      development, maintenance or progression of cancer of the exocrine pancreas. While
      the role that these point mutations play in any or all of these processes remains
      to be determined, their presence is useful clinically for the diagnosis of
      pancreatic carcinoma at the molecular genetic level. The detection of mutated c-K
      ras oncogenes in fine needle aspirates of pancreatic masses, that by
      cytomorphology may be suspicious but not diagnostic of malignant disease,
      increases the sensitivity of the diagnosis for this cancer. The identification of
      codon 12 mutations in the c-K-ras gene in pancreatic adenocarcinomas has been
      possible by advances in recombinant DNA techniques, especially by the development
      of in vitro gene amplification by the polymerase chain reaction (PCR). The
      possibility of analysing formalin-fixed, paraffin-embedded tissue for the
      presence of genetic alterations as small as single point mutations by PCR in
      concert with other mutation detection techniques, should facilitate the molecular
      genetic analysis of pancreatic carcinoma. Retrospective studies using stored
      specimens are now feasible with the technology described and should yield
      important information on the molecular epidemiology and aetiology of this and
      other diseases.

PMID- 1976392
TI  - In vitro modulation of normal and diseased human neutrophil function by
      pentoxifylline.
AB  - The influence of pentoxifylline on normal and diseased neutrophil function has
      been studied in vitro. In high concentrations pentoxifylline stimulated human
      neutrophil chemotaxis toward both bacterial oligopeptides and complement
      components. Pentoxifylline was also shown in vitro to restore the normal
      chemotactic capacity of neutrophils from patients with known functional defects,
      i.e. myelodysplastic syndromes, lazy leucocyte syndrome, juvenile parodontitis,
      hyper-IgE-syndrome and liver cirrhosis. Pentoxifylline was also shown to strongly
      inhibit the release of primary and secondary granule release of granulocytes.
      Moreover, pentoxifylline inhibits both basal and stimulated neutrophil adhesion
      to both aortic and pulmonary artery calf endothelium. The mechanism whereby
      pentoxifylline exerts this action is not adequately understood. While our results
      partially imply interference of pentoxifylline with neutrophil cyclic AMP and/or
      prostaglandin metabolism, down-regulation of neutrophil functional antigen (e.g.
      CD11, CD18) expression seems to play a key role in the observed drug effects.
      Finally, these results indicate that pentoxifylline may be useful in the
      treatment of granulocyte mediated diseases and symptoms.

PMID- 1976395
TI  - Coeliac disease.

PMID- 1976396
TI  - Growth control factors in the gastrointestinal tract.

PMID- 1976397
TI  - Gastrinoma syndrome in multiple endocrine neoplasia.

PMID- 1976398
TI  - An unusual pattern of hemopoietic reconstitution in patients with acute myeloid
      leukemia transplanted with autologous recovery phase peripheral blood.
AB  - Fourteen patients with acute myeloid leukemia (AML) were autotransplanted with
      peripheral blood cells collected during early remission. Seven were
      autotransplanted in first relapse and seven in first remission. They received a
      median of 3.3 X 10(8) nucleated cells/kg body weight (BW) and 92 X 10(4) myeloid
      progenitor cell (CFU-GM) per kg BW. Rapid hemopoietic reconstitution (HR)
      occurred in all patients with median time to reach normal neutrophil and platelet
      counts 13 and 18 days post re-infusion respectively. However, in three patients
      neutrophil counts fell to less than 1.0 x 10(9)/l and in seven patients platelet
      counts fell to less than 25 x 10(9)/l between 26 and 40 days post-transplant
      (trough count). In all but two patients who received the lowest CFU-GM dose the
      counts returned to normal or near normal levels (steady count). There were
      significant correlations between the CFU-GM dose and the trough and the steady
      platelet counts (p = 0.04 and 0.01 respectively). Patients receiving more than 50
      x 10(4) CFU-GM/kg BW had higher steady neutrophil and platelet counts (p = 0.011
      and 0.033 respectively) although some patients receiving greater than 50 x 10(4)
      CFU-GM/kg still experienced thrombocytopenia during the second month post graft.
      There was no significant correlation between the nucleated cell dose and HR. The
      cause of the fall in platelet and neutrophil counts in the second month post
      graft is not clear but is probably a reflection of a proliferative defect in the
      recovery phase stem cells in AML.

PMID- 1976399
TI  - Durable and complete hematopoietic reconstitution after autografting of rhGM-CSF
      exposed peripheral blood progenitor cells.
AB  - Two patients with poor prognosis stage III multiple myeloma have been treated
      with myeloablative chemoradiotherapy, i.e. 10 Gy fractionated total body
      irradiation plus 120 mg/m2 intravenous melphalan, and then transplanted with
      autologous peripheral blood cells harvested by four leukaphereses during the
      phase of rapid hematopoietic recovery following induction therapy with high-dose
      (2 g/m2) etoposide and recombinant human glycosylated granulocyte macrophage
      colony stimulating factor (rhGM-CSF). Following myeloablative therapy and
      autologous peripheral blood cell transplantation, both patients experienced brief
      pancytopenia followed by rapid hematopoietic recovery of leukocytes (time to
      greater than 500 x 10(6)/l = 12 days) and platelets (time to greater than 100 x
      10(9)/l = 14 days). In particular, single donor platelet transfusion requirements
      were limited to one and two transfusions per patient, respectively.
      Reconstitution has so far been maintained throughout the follow-up period for the
      two patients (9 and 6 months, respectively). These two cases show that rhGM-CSF
      exposed peripheral blood cells are capable of producing prompt and sustained
      hematopoietic reconstitution in patients treated with myeloablative
      chemoradiotherapy.

PMID- 1976401
TI  - In vitro inhibition of intestinal motility by phenylethanolaminotetralines:
      evidence of atypical beta-adrenoceptors in rat colon.
AB  - 1. The new compounds phenylethanolaminotetralines (PEAT), unlike the reference
      beta-adrenoceptor agonists isoprenaline (Iso), ritodrine (Ri) and salbutamol
      (Sal), produced half-maximal inhibition of spontaneous motility of rat isolated
      proximal colon at substantially lower concentrations (EC50 2.7-30 nM) than those
      inducing beta 2-adrenoceptor-mediated responses (relaxation of guinea-pig
      isolated trachea and rat uterus) and had virtually no chronotropic action (EC50
      greater than 3 x 10(5) M) on the guinea-pig isolated atrium (a beta 1
      adrenoceptor-mediated response). 2. The nonselective beta-adrenoceptor
      antagonists alprenolol and propranolol prevented the inhibition of rat colon
      motility by the PEAT with low and different potencies (pA2 values around 7.5 and
      6.5 respectively). Conversely alprenolol and propranolol had a higher and similar
      potency (pA2 values around 9.0) in preventing typical beta 1 or beta 2-responses
      (increase in atrial frequency by Iso or tracheal relaxation by Ri or Sal). 3. The
      selective beta-adrenoceptor antagonists CGP 20712A (beta 1) and ICI 118,551 (beta
      2) either alone or in combination, did not prevent rat colon motility inhibition
      by the representative PEAT SR 58611A, which was also fully resistant to alpha
      adrenoceptor, acetylcholine, dopamine, histamine, opioid and 5-hydroxytryptamine
      antagonists. 4. These results indicate that the PEAT are a new class of beta
      adrenoceptor agonists and suggest that their preferential intestinal action may
      be accounted for by selectivity for atypical beta-adrenoceptors, abundant in the
      rat colon and distinct from the currently recognized beta 1 and beta 2 subtypes.

PMID- 1976400
TI  - The role of alpha- and beta-adrenoceptor subtypes in mediating the effects of
      catecholamines on fasting glucose and insulin concentrations in the rat.
AB  - 1. The role of alpha- and beta-adrenoceptor subtypes in the regulation of plasma
      glucose and immunoreactive insulin (IRI) levels has been investigated in normal
      conscious fasted rats by employing selective agonists and antagonists. 2.
      Adrenaline (0.2 mg kg-1)-induced hyperglycaemia was abolished by the selective
      alpha 2-adrenoceptor antagonist idazoxan (1.0 mg kg-1), unaltered by non
      selective beta-adrenoceptor blockade (propranolol, 1.0 mg kg-1) and potentiated
      by the selective alpha 1-adrenoceptor antagonist prazosin (0.3 mg kg-1).
      Adrenaline increased plasma IRI levels in the presence of idazoxan but not in the
      presence of either prazosin or propranolol. 3. The selective alpha 2-adrenoceptor
      agonists UK 14304 (0.1 and 0.3 mg kg-1) and BHT-920 (0.2 and 0.5 mg kg-1)
      elicited dose-dependent hyperglycaemic responses, but did not alter plasma IRI
      levels. UK 14304 (0.1 mg kg-1)-evoked hyperglycaemia was blocked by idazoxan but
      not by prazosin. 4. The selective alpha 1-adrenoceptor agonists methoxamine (0.3
      mg kg-1) and phenylephrine (0.3 mg kg-1) failed to modify either plasma glucose
      or IRI levels. 5. Isoprenaline (0.2 mg kg-1) elicited hyperglycaemic and
      insulinotropic responses which were attenuated by propranolol (1.0 mg kg-1) and
      the selective beta 2-adrenoceptor antagonist ICI 118551 (1.0 mg kg-1), but not by
      the beta 1-selective antagonists atenolol (1.0 mg kg-1) and betaxolol (1.0 mg kg
      1). 6. None of the antagonists per se affected basal plasma glucose or IRI
      concentrations, except prazosin (1.0 mg kg-1). 7. The results indicate that
      adrenoceptors do not appear to be involved in regulating basal plasma glucose and
      IRI concentrations in the fasted rat. However, the effects of catecholamines on
      these parameters are mediated by alpha 2- and beta 2-adrenoceptors, whereas
      alpha,- or beta l-adrenoceptors do not appear to be involved.

PMID- 1976402
TI  - Effect of 6-cyano-2,3-dihydroxy-7-nitro-quinoxaline (CNQX) on dorsal root-, NMDA
      , kainate- and quisqualate-mediated depolarization of rat motoneurones in vitro.
AB  - 1. Mature in vitro rat spinal cord preparations have been used to compare the
      depressant effects of 6-cyano-2,3-dihydroxy-7-nitroquinoxalinedione (CNQX) and
      kynurenate on transmission from low threshold myelinated primary afferents in
      dorsal roots. EC50 values +/- s.e.mean (number of preparations in parentheses)
      for depression of the monosynaptic ventral root reflex were respectively 1.0 +/-
      0.3 microM (5) and 135 +/- 15 microM (3) for CNQX and kynurenate. Transmission
      through superior cervical ganglia was not significantly affected by
      concentrations of CNQX up to 100 microM or kynurenate up to 5 mM. 2. Immature in
      vitro rat spinal cord preparations were used to measure dose-ratios for
      antagonism of depolarizations induced by N-methyl-D-aspartate (NMDA), kainate or
      quisqualate by 4, 10 and 25 microM CNQX. In the presence of 0.75 mM Mg2+ pA2
      values +/- s.e.mean were respectively 4.62 +/- 0.05 (16), 5.79 +/- 0.01 (4) and
      5.59 +/- 0.05 (16) for each agonist. These values were not significantly altered
      in the absence of added Mg2+. The mean pA2 values for kainate were significantly
      higher than those for quisqualate (P less than 0.01). 3. Antagonism of NMDA
      induced depolarizations was evident at 10 and 25 but not 4 microM CNQX. The
      antagonism of NMDA was reversed by D-serine (100 and 200 microM). 4. A similarity
      between the relative potencies of both CNQX and kynurenate for depression of
      synaptic transmission and antagonism of amino acid-induced depolarizations
      indicates that monosynaptic transmission from myelinated primary afferents to
      motoneurones is mediated by kainate and/or quisqualate sub-types of non-NMDA
      receptors.

PMID- 1976403
TI  - Identification of human platelet alpha 2-adrenoceptors with a new antagonist [3H]
      RX821002, a 2-methoxy derivative of idazoxan.
AB  - 1. The binding of a new alpha 2-adrenoceptor antagonist, [3H]-RX821002 (2-(2
      methoxy-1,4-benzodioxan-2-yl)-2-imidazoline), was investigated in human platelet
      membranes and compared with [3H]-yohimbine binding parameters. 2. Analysis of
      kinetic data revealed association and dissociation time courses consistent with a
      simple biomolecular reaction. Saturation isotherms showed that [3H]-RX821002
      labelled a higher total number of alpha 2-binding sites (224 +/- 31 vs 168 +/- 24
      fmol mg-1 protein) than [3H]-yohimbine and with higher affinity (Kd: 0.92 +/-
      0.06 vs 1.51 +/- 0.08 nM). Moreover [3H]-RX821002 exhibited a lower percentage of
      nonspecific binding 3. The difference in total binding is due to a better
      labelling of the alpha 2-adrenoceptors in the low affinity state by [3H]-RX821002
      since the labelled receptors number in high affinity state was identical with the
      two radioligands. 4. [3H]-RX821002 binding displayed a specificity similar to
      that obtained with [3H]-yohimbine. The potency of various compounds acting on
      adrenoceptors was: yohimbine greater than oxymetazoline greater than UK14304
      greater than (-)-adrenaline greater than prazosin greater than or equal to (+)
      adrenaline greater than isoprenaline. This order of potency is classical for an
      alpha 2A-adrenoceptor. 5. RX821002 is a more potent alpha 2-adrenoceptor
      antagonist than yohimbine on adrenaline-induced platelet aggregation. 6. These
      results indicate that [3H]-RX821002 is a suitable ligand for the identification
      of human platelet alpha 2-adrenoceptors.

PMID- 1976404
TI  - Drug prescribing for schizophrenic out-patients on depot injections. Repeat
      surveys over 18 years.
AB  - Serial surveys of the prescribing practices of psychiatrists for schizophrenic
      out-patients over 1970-88 showed important changes. During the interval 1970-83,
      polypharmacy and the use of multiple neuroleptics were reduced. The total dose of
      neuroleptics prescribed fell and the proportion administered by depot injection
      increased. Since 1983, however, some of these favourable trends have been
      reversed. Prescribing practices may also vary between teaching and non-teaching
      hospitals.

PMID- 1976405
TI  - Psychiatry and ethnic groups.

PMID- 1976406
TI  - Selective sensitization by L-glutamate of baroreflex-mediated bradycardia
      following microinjection into the rostral ventrolateral medulla.
AB  - This study examined the role of L-glutamate receptors in different sites in the
      rostral ventrolateral medulla (RVL) on baseline mean arterial pressure (MAP),
      heart rate (HR), sympathetic efferent discharge (SED) as well as baroreflex
      control of HR and SED. Depending on the site, the hemodynamic responses varied
      from an increase to a decrease in MAP which was accompanied by a similar or an
      opposite change in HR; the change in SED correlated positively with the change in
      MAP. Because injection of the test dose of glutamate (5 nM) into the deepest
      portion of the RVL produced the most pronounced increases in MAP, which was
      accompanied by a brisk bradycardia, we decided to investigate the nature of these
      responses. Dose-related sympathoexcitatory, pressor and bradycardic effects were
      obtained in response to 1, 3, 5 and 10 nM glutamate. The glutamate antagonist,
      glutamate diethylester (GDEE) abolished these responses and decreased baseline
      MAP, HR and SED. That glutamate-evoked bradycardia was baroreceptor-mediated was
      supported by: (1) the bradycardia was not only eliminated but was also converted
      to a small but significant tachycardic response in sinoaortic denervated rats and
      following cardiac muscarinic blockade; (2) glutamate substantially sensitized the
      baroreceptor HR and had no effect on SED response when tested by phenylephrine;
      and (3) GDEE abolished the sensitizing action of glutamate on the baroreflex
      control of HR. We conclude that glutamatergic pathways in the deepest portion of
      the RVL are tonically active and subserve sympathoexcitatory, pressor and
      tachycardic effects. Also, glutamate differentially sensitizes the baroreceptor
      reflex pathways that control HR by mainly activating the vagal component of the
      reflex, an effect which masks its tachycardic effect.

PMID- 1976408
TI  - Differential blockade of early and late components of acoustic startle following
      intrathecal infusion of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) or D,L-2
      amino-5-phosphonovaleric acid (AP-5).
AB  - The present study investigated the individual contributions of spinal cord N
      methyl-D-aspartate (NMDA) and non-NMDA receptors to the acoustic startle reflex
      in rats. The first experiment measured whole body acoustic startle before and
      after intrathecal infusion of various doses of either the NMDA receptor
      antagonist, D,L-2-amino-5-phosphonovaleric acid (AP-5), or the non-NMDA
      antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Both compounds depressed
      startle in a dose-dependent fashion with similar potencies. A second experiment
      measured startle electromyographically (EMG) in the quadriceps femoris muscle
      complex in the hindlimbs during auditory stimulation to characterized the effects
      of these two compounds on the early (approximately 8 ms) or late (approximately
      15 ms) EMG components of the startle response. CNQX preferentially blocked the
      early EMG component of startle, whereas AP-5 preferentially blocked the late
      component. These results suggest that the acoustic startle reflex involves an
      early EMG component mediated by spinal non-NMDA receptors, and a late EMG
      component mediated by spinal NMDA receptors.

PMID- 1976407
TI  - Immunohistochemical evidence for synaptic connections between neuropeptide Y
      containing axons and periventricular somatostatin neurons in the anterior
      hypothalamus in rats.
AB  - By employing a pre-embedding double immunolabeling technique, we examined light
      and electron microscopically synaptic associations between neuropeptide Y (NPY)
      containing axons and somatostatin (SRIH)-containing neurons in the anterior
      periventricular area (APV) of the rat hypothalamus. For light microscopy, the
      immunoreactions for NPY and SRIH were visualized with silver-gold and
      diaminobenzidine (DAB), respectively, and the reverse labeling was used for
      electron microscopy. Light microscopy disclosed many brown SRIH perikarya
      surrounded by several black beads of NPY fibers in the APV. In electron
      microscopy, immunoreactive SRIH neurons revealed silver-gold particles scattered
      throughout the cytoplasm and accumulated in the Golgi area and the secretory
      granules. SRIH perikarya and dendritic processes indicated synaptic associations
      with DAB-labeled NPY fiber terminals and immunonegative fibers. NPY presynaptic
      terminals possessed numerous small clear vesicles and a few dense core vesicles;
      vesicular membranes and cores were labeled with DAB chromogen. Both the pre- and
      postsynaptic membranes were thickened equally to be a symmetric synapse. These
      findings suggest that NPY neurons are involved in the regulation of growth
      hormone secretion from the pituitary by affecting periventricular SRIH neurons.

PMID- 1976409
TI  - Chemical stimulation of the nucleus tractus solitarii decreases cerebral blood
      flow in anesthetized rats.
AB  - In anesthetized (chloralose and urethane), paralyzed and artificially ventilated
      rats, the neurons in the nucleus tractus solitarius (NTS) were chemically
      stimulated by microinjections of L-glutamate and the cerebral blood flow (CBF)
      was determined using a combination of labeled microspheres (either 57Co, 113Sn
      and 46Sc or 141Ce, 85Sr and 46Sc). Unilateral chemical stimulation of the NTS (n
      = 14) decreased CBF significantly in most brain areas. The decrease in CBF was
      not due to the decrease in arterial blood pressure (ABP) because the CBF of the
      whole cerebral cortex during the chemical stimulation of the NTS was
      significantly smaller (P less than 0.05) than the CBF during controlled
      hemorrhagic hypotension (n = 10). In another group of rats (n = 6), moderate
      hypertension was induced by blood transfusion. Unilateral chemical stimulation of
      the NTS in these rats decreased ABP but it remained within normotensive range. A
      significant (P less than 0.05) decrease in CBF (from 62 +/- 28 (mean +/- S.D.) to
      48 +/- 23 ml.min-1.(100 g)-1) and increase in cerebrovascular resistance (from
      1.9 +/- 1.2 to 2.6 +/- 1.2 mm Hg per [ml.min-1.(100 g)-1]) was observed in the
      whole cerebral cortex of these rats. Chemical stimulation of the NTS did not
      affect the reactivity of the cerebral vessels to hypercapnea (n = 5). These
      results suggest that the cell bodies within the NTS may play a role in the
      control of cerebral circulation.

PMID- 1976410
TI  - Effect of aspartame on N-methyl-D-aspartate-sensitive L-[3H]glutamate binding
      sites in rat brain synaptic membranes.
AB  - Aspartame (L-aspartyl-L-phenylalanine methyl ester), an artificial low-calorie
      sweetener, was shown to dose-dependently inhibit L-[3H]glutamate binding to its N
      methyl-D-aspartate-specific receptors. L-Aspartic acid, a major endogenous
      metabolite of aspartame, inhibited the binding more stronger than aspartame,
      while the other metabolites, L-phenylalanine and methanol, had no effect at the
      same concentration. Aspartame caused a significant change in the affinities of L
      [3H]glutamate binding without altering the Vmax values of the binding, suggesting
      the inhibition is competitive. These in vitro findings suggested that aspartame
      may act directly on the N-methyl-D-aspartate-sensitive glutamate recognition
      sites in the brain synaptic membranes.

PMID- 1976411
TI  - Differential effects of advancing age on neurotransmitter cell loss in the
      substantia nigra and striatum of C57BL/6N mice.
AB  - The present study was carried out to examine the extrapyramidal motor system of
      C57BL/6N mice for age-related cell loss in cholinergic neurons of the striatum
      (ST) and dopaminergic (DA) neurons of the substantia nigra (SN).
      Immunocytochemistry using antibodies against tyrosine hydroxylase (TH) or choline
      acetyltransferase (CAT) were used to identify DA or cholinergic neurons of the SN
      and ST in 6 age groups of young (3 months), middle (6, 10, 20 months) and old
      (25, 30 months) aged mice. We found that while there was a small decline (11%) in
      the total number of DA neurons of the SN with age, this decrease did not reach
      statistical significance. In contrast, the total number of cholinergic neurons of
      the ST significantly decreased between 25 and 30 months of age with the largest
      cell loss (38%) found in the rostral ST. In addition, the loss of cholinergic
      neurons in 30-month-old mice was paralleled by a decline in the mean cross
      sectional area of the cell soma and nucleus of remaining cholinergic neurons.
      These data suggest that advancing age has a differential effect on
      neurotransmitter neurons of the SN and ST and supports the notion that cell loss
      is not an inevitable characteristic of senescence but is brain region- and cell
      type-specific. In addition, these data are consistent with the hypothesis that
      the proliferation of striatal dendrites described previously in aged C57BL/6N
      mice may result, in part, from a compensatory growth of these processes secondary
      to age-related cell loss of striatal neurons.

PMID- 1976413
TI  - Characterization and mechanism of glutamate neurotoxicity in primary striatal
      cultures.
AB  - Excitatory amino acids may play a role in the pathogenesis of cell death in
      neurodegenerative diseases, including Huntington's disease (HD). In an attempt to
      develop a tissue culture model for HD, the toxicity of glutamate was examined in
      primary striatal cultures derived from newborn rats. Morphological criteria were
      used to determine the toxic effects of glutamate in 6-, 12-, and 18-day-old
      cultures which were examined before and after 1-3 h of exposure to glutamate.
      Although younger cultures demonstrated little susceptibility to glutamate
      relative to controls, the number of neurons in older cultures was significantly
      depleted in the presence of glutamate. Glutamate toxicity was dose-dependent,
      with an ED50 of approximately 300 microns glutamate, and a maximal effect was
      observed within 3 h of initial exposure. Affected neurons demonstrated somal
      swelling within 1 h of glutamate exposure and disruption of neuritic processes
      and somal integrity within 3 h. Cell death was significantly increased by raising
      the extracellular calcium concentration and could be decreased by the addition of
      magnesium to the incubation medium. Moreover, the N-methyl-D-aspartate (NMDA)
      receptor agonist, quinolinic acid, showed a toxicity profile similar to that of
      glutamate. The NMDA receptor competitive antagonist, 2-amino-5-phosphonovalerate
      (APV) significantly reduced toxicity, albeit incompletely. An additional
      component of glutamate mediated toxicity in striatal cultures could be explained
      by activation of non-NMDA receptor subtypes. These in vitro studies indicate that
      glutamate is toxic to a subset of mature striatal neurons in the absence of a
      glutamatergic afferent input, and that this toxicity is mediated partially by the
      NMDA receptor, with an additional component due to non-NMDA receptors.

PMID- 1976412
TI  - Somatostatin-immunoreactive neurons in the rat striatum: effects of
      corticostriatal and nigrostriatal dopaminergic lesions.
AB  - The present study examined the effects of the impairment of corticostriatal and
      nigrostriatal dopaminergic transmission on the mean number and the topographical
      distribution of somatostatin-containing neurons in frontal sections of the rat
      rostral striatum. These neurons, visualized by an immunohistochemical method
      using a specific anti-somatostatin(28) antibody were shown to be unevenly
      distributed; the number of immunoreactive perikarya being consistently lower in
      the dorsolateral and higher in the middle areas of striatal sections than in the
      remaining parts of the structure. Such a distribution and number were not altered
      either by unilateral 6-hydroxydopamine (6-OHDA)-induced lesion of the
      nigrostriatal dopaminergic neurons after 2- to 3-week survival periods, or by
      alpha-methylparatyrosine-induced dopamine depletion. In animals with similar 6
      OHDA-induced lesions, no change in the striatal concentration of somatostatin
      measured by radioimmunoassay was observed. These results suggest that
      somatostatin levels in striatal neurons are not under a dopaminergic influence in
      contrast to that previously described for neuropeptide Y, although both peptides
      are thought to coexist extensively in the same striatal neuron population. On the
      contrary, extensive unilateral frontoparietal ablation of the cerebral cortex
      elicited, 2-3 weeks later, a significant increase in the mean number of
      somatostatin-immunoreactive cells per section in the ipsilateral striatum
      preferentially localized to the dorsolateral zone of the structure with no change
      in the contralateral side. Data from immunohistochemical studies were further
      discussed in comparison with results obtained by radioimmunoassay showing that
      similar cortical lesion induced no change in somatostatin endogenous levels in
      the ipsilateral striatum and a 30% decreased concentration of the peptide in the
      contralateral striatum. These data suggest that the corticostriatal pathway
      influences the expression of somatostatin at either a translational, processing
      or metabolic level in a topographically restricted population of striatal
      somatostatin-containing neurons.

PMID- 1976414
TI  - The correlation between excitatory amino acid-induced current responses and
      excitotoxicity in striatal cultures.
AB  - Neuronal excitotoxic injury is initiated by activation of specific excitatory
      amino acid receptors and is mediated by ion flow through associated ion channels.
      In a companion paper we defined the age dependence of glutamate toxicity in
      striatal cultures. In this study we examined the correlation between age
      dependent changes in the electrophysiologic responses to glutamate and N-methyl-D
      aspartate (NMDA) and the development of excitotoxicity. Currents were recorded in
      voltage-clamped neurons in response to the pressure application of glutamate or
      NMDA. We found that 1-week-old cultures were resistant to excitotoxic effects of
      1 or 3 mM glutamate (Freese et al., companion paper). Neurons from cultures of
      this age often did not exhibit current responses when exposed to NMDA (10 microM
      or 100 microM). However, most neurons were responsive to 10 microM glutamate.
      After 12 days in culture the current responses induced by NMDA were more
      prevalent and shifted toward higher amplitudes. These changes in NMDA current
      responses coincided temporally with major increases in excitotoxic sensitivity.
      However, we then found that excitotoxic susceptibility doubled between 12 and 18
      days in culture without any parallel increase in glutamate- or NMDA-induced
      currents. Additionally, neurons which survived 1 mM glutamate exposure for 3 h
      were found to exhibit glutamate and NMDA responses. These data show that the
      expression of excitatory amino acid-induced currents is a prerequisite for
      excitotoxicity, but that additional factors must also contribute to the full
      maturation of in vitro neuronal vulnerability.

PMID- 1976415
TI  - Neuron-associated astroglial cells express beta- and alpha 1-adrenergic receptors
      in vitro.
AB  - In vivo, astroglial cells are closely interrelated with neurons. The present
      studies were undertaken to determine if certain astroglial properties are
      influenced when maintained in a heterogeneous cellular environment. Astrocytes
      and neurons were co-cultured from hippocampal tissue and the parameters examined
      included astroglial morphology and expression of beta- and alpha 1-adrenergic
      receptors (AR). Astroglial cells exhibit an extremely elongated morphology when
      growing in direct contact with neurons. Astroglia growing under the same culture
      conditions, but not in direct contact with neurons, exhibited a polygonal
      morphology. One hundred percent of the elongated astroglia expressed the beta-AR
      with an average density of 1320 binding sites/1000 microns 2. In contrast, only
      40-50% of these elongated astroglia expressed alpha 1-ARs. Our results indicate
      that astroglia, maintained in the presence of neurons, continue to express beta-
      and alpha 1-ARs. These results suggest that under in vivo conditions, where
      astroglia normally exist in close contact with neurons, astrocytes may express
      surface receptors which enable them to sense neuronal activity and to selectively
      respond to such activity. The elongated astroglia described here may exhibit
      morphological features more reminiscent to that which exists in vivo.

PMID- 1976416
TI  - Characterization of the origins of astrocyte response to injury using the
      dopaminergic neurotoxicant, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.
AB  - We used the dopaminergic neurotoxicant, 1-methyl-1,2,3,6-tetrahydropyridine
      (MPTP), as a tool to characterize the origins of astroglial response to injury.
      Radioimmunoassay of the astrocyte protein, glial fibrillary acidic protein
      (GFAP), was used to quantify the astrocyte reaction to MPTP. Assays of neuron
      localized proteins and of dopamine were used to assess neuronal damage caused by
      MPTP. A single administration of MPTP (12.5 mg/kg, s.c.) to the C57BL/6J mouse
      resulted in more than a 3-fold increase in striatal GFAP within 48 h, followed by
      a decline to baseline at 3 weeks. A decrease in the amount of striatal tyrosine
      hydroxylase (TH), a marker of dopaminergic neurons, preceded the rise in GFAP.
      The concentration of striatal DARPP-32, a phosphoprotein enriched in neurons
      receiving dopaminergic input, was not affected by MPTP. Protecting the
      dopaminergic neurons from the neurotoxic metabolite of MPTP, 1-methyl-4
      phenylpyridinium (MPP+), either by blocking its formation or by preventing its
      uptake into dopaminergic neurons, completely blocked the increase in GFAP. MPTP
      did not appear to disrupt the blood-brain barrier, therefore, blood-borne
      elements probably did not mediate the increase in GFAP. In addition, immunoblot
      data indicated that brain-derived interleukin 1, an astrocyte growth factor, also
      did not play a role in MPTP-induced gliosis. Together, these findings suggest
      that diffusible factors derived from damaged dopaminergic neurons initiate the
      astrocyte response to MPTP and that large increases in GFAP can be induced
      without the participation of serum-derived growth factor.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1976417
TI  - Correlation between acetylcholine release and recovery of conditioned taste
      aversion induced by fetal neocortex grafts.
AB  - Rats with lesions of the gustatory neocortex (GN) show deficits in the
      acquisition of taste aversion. Fetal GN grafts to a lesioned animal restore taste
      aversion learning and establish connections with the host brain. In this work, we
      examined whether the grafts are biochemically functional and whether this fact
      can be related to behavioral recovery. Gustatory or occipital cortices from rat
      fetuses were transplanted to GN-lesioned rats. Two months later, taste aversion
      recovery was tested and the release of labeled gamma-aminobutyric acid (GABA),
      acetylcholine (ACh), dopamine and glutamate from the grafted tissue was assayed.
      Fetal GN grafts promoted recovery of learning and released GABA, ACh and
      glutamate in response to K+ depolarization. Occipital cortex grafts did not
      induce behavioral recovery, although they were capable of releasing GABA. In
      contrast, these grafts did not release ACh. Moreover, GN-grafted rats in which
      behavioral recovery was not seen also failed to release ACh. These results are in
      agreement with previous findings that cholinergic transmission is important in
      the GN and suggest that ACh may play a role in the graft-mediated behavioral
      recovery observed in this model.

PMID- 1976418
TI  - Ultrastructural evidence for a close relationship between dopamine cell processes
      and blood capillary walls in Macaca monkey and rat retina.
AB  - In the retina, tyrosine-hydroxylase (TH) antiserum specifically labels intrinsic
      dopamine (DA)-neurons. In order to clarify the relationship between capillaries
      and DA-processes already observed by light microscopy, we have performed TH
      immunocytochemistry on rat and monkey retinas at the electron microscope level.
      Close contacts were observed between DA-varicosities and the basal lamina of both
      pericytes and endothelial cells. As in the brain, these anatomical findings
      suggest that intrinsic DA-neurons could contribute to the regulation of local
      retinal blood flow and/or permeability.

PMID- 1976419
TI  - Cholecystokinin octapeptide antagonized opioid analgesia mediated by mu- and
      kappa- but not delta-receptors in the spinal cord of the rat.
AB  - Intrathecal (ith) injection of cholecystokinin octapeptide (CCK-8) to the rat
      with single dose of 4 or 40 ng, or successive doses from 0.1 to 1 microgram at 10
      min intervals produced neither analgesia nor hyperalgesia. However, the analgesia
      produced by ith injection of PL017, a specific mu-receptor agonist or 66A-078, a
      specific kappa-receptor agonist could be markedly antagonized by CCK-8 at a dose
      as small as 4 ng. In contrast, analgesia produced by ith injection of delta
      agonist DPDPE could not be blocked by CCK-8 even at a dose as high as 40 ng.
      Since the effect of CCK-8 could be totally reversed by the CCK receptor
      antagonist proglumide, this effect is most probably mediated by CCK receptors.

PMID- 1976421
TI  - Effects of GABA and anxiolytics on the single unit discharge of suprachiasmatic
      neurons in rat hypothalamic slices.
AB  - The effects of gamma-aminobutyric acid (GABA), muscimol, baclofen and the
      anxiolytics; diazepam (DZP), flurazepam (FZP) and zopiclone on single-unit neural
      activities in the suprachiasmatic nucleus (SCN) were investigated using the rat
      hypothalamic slice preparation. Exposure of the slice to GABA 10(-4) M produced
      inhibitory responses in 65% of the 49 SCN neurons examined. The threshold
      concentration of GABA ranged from 10(-6) to 10(-4) M. Neurons responsive to GABA
      were not found to be restricted to a subdivision of the SCN, but were diffusely
      distributed throughout the nucleus. DZP, FZP and zopiclone produced responses
      similar to those of GABA. The inhibitory effects of GABA (10(-5) M) were
      potentiated by coadministration of DZP (10(-5) M). Muscimol and baclofen (10(-7)
      M to 10(-4) M) also inhibited SCN neuronal activity in a dose-dependent manner.
      Bicuculline (10(-5) M-10(-4) M) scarcely affected the baclofen-induced inhibition
      (1/6) but strongly antagonized the effects of muscimol (6/6), GABA (6/8) and DZP
      (4/5). These results suggest that the receptors mediating the inhibitory effects
      of GABA and anxiolytics within the SCN may be GABAA and/or GABAB or GABA-BDZ
      receptor complex, respectively.

PMID- 1976420
TI  - Effect of opioids on acetylcholine release evoked by K+ or glutamic acid from rat
      neostriatal slices.
AB  - Endogenous acetylcholine (ACh) release from rat striatal slices was measured by a
      chemiluminescent method. Several opiate agents were tested for their ability to
      modulate ACh release evoked by potassium ions (K+) or glutamic acid (GLU).
      Morphine, [D-Ala2,Gly(0l)5]-enkephalin (DAGO), [D-Ala2,D-Leu5]-enkephalin (DADLE)
      and [D-Pen2-D-Pen5]-enkephalin (DPDPE) were found to have an inhibitory effect on
      K(+)- or GLU-evoked ACh release. This effect was completely blocked by naloxone,
      but this antagonist by itself had no effect on ACh release. The action of mu
      opiate agonists (morphine and DAGO) on ACh release evoked by K+ was sensitive to
      tetrodotoxin (TTX), but that of delta-opiate agonists (DADLE and DPDPE) was
      insensitive. The release evoked by GLU was abolished in the presence of TTX. The
      activation of kappa-opiate receptor by dynorphin-(1-13) had no effect on K(+)- or
      GLU-evoked ACh release. It is concluded that mu- and delta-opiate agonists, but
      not kappa, exert an inhibitory control on striatal cholinergic interneurons, but
      with a different mechanism of action of localization of the receptors.
      Corticostriatal glutamatergic neurons have an important role in the interaction
      of the ACh-opioid systems.

PMID- 1976422
TI  - Interaction between the alpha 2-noradrenergic and muscarinic systems in the
      regulation of neocortical high voltage spindles.
AB  - The present experiments were carried out in order to study the interaction
      between alpha 2-noradrenergic and muscarinic systems in regulating high voltage
      spindle (HVS) activity in neocortex. Alpha 2-antagonist (atipamezole 1 and 10
      mg/kg) blocked HVS activity. Atipamezole at 0.1 mg/kg dose had no effect on HVS
      activity. Alpha 2-agonist (guanfacine 0.004, 0.02 and 0.1 mg/kg) increased dose
      dependently HVSs. Guanfacine-induced HVSs were blocked by nucleus reticularis
      (NRT) lesions and by stimulation of either noradrenergic or cholinergic
      (pilocarpine) systems. Moreover, combined injections of atipamezole 1 mg/kg and
      pilocarpine 3 mg blocked HVSs more effectively than either of the drugs alone.
      Our results suggest that the NRT is jointly modulated by the noradrenergic and
      cholinergic afferents.

PMID- 1976423
TI  - Adrenal responses and neurotransmitters in posterior hypothalamic
      deafferentation.
AB  - The effects of a small posterior hypothalamic deafferentation (PHD) on
      adrenocortical responses to peripheral neural stimuli were investigated in rats.
      PHD inhibited the rise in plasma corticosterone (CS) following photic and
      acoustic stimulation, but did not affect the adrenocortical response following
      sciatic nerve stimulation. PHD did not change the content of norepinephrine in
      the paraventricular nucleus of the hypothalamus, however, it reduced the
      serotonin content by about 30%. The possible role of serotonin or of another
      tonic caudal input into the hypothalamus for the activation of the pituitary
      adrenocortical axis, following certain neural stimuli, is discussed.

PMID- 1976424
TI  - Glutamate modulates dopamine release in the striatum as measured by brain
      microdialysis.
AB  - Brain microdialysis plus high performance liquid chromatography and
      electrochemical detection were employed to study whether glutamate exerts direct
      presynaptic facilitation of dopamine (DA) release in the rat striatum. The
      perfusion of the dialysis probe with high-K+ Ringer solution (70 mM) increased DA
      and glutamate release 380.6 +/- 69.2% and 323.0 +/- 46.6% of preperfusion levels,
      respectively. Perfusion of 1 mM glutamate stimulated DA release by 250.7 +/-
      30.6%, and coadministration of 2 mM glutamic acid diethylester (glutamate
      receptor blocking agent) significantly antagonized the glutamate response. The
      present results indicate presynaptic facilitation of the release of DA in the
      striatum by glutamate.

PMID- 1976425
TI  - [Implication of alpha-2 adrenergic post-synaptic receptors in the central
      catecholaminergic stimulation of the corticotropic axis in rats].
AB  - We have recently assigned a major stimulatory role to the brain catecholamines
      (CA) via alpha 1 and beta receptors on CRH-ACTH secretion, e.g. in the
      physiological response to stress. In the present study, we explored the possible
      participation in this regulation of post-synaptic alpha 2 receptors in free
      moving rats, one week after CA denervation of the hypothalamus by bilateral
      neurotoxic lesions of the noradrenergic ascending brain stem bundles (NAB).
      Intracerebroventricular (i.c.v.) injection of clonidine (alpha 2 agonist; 1 nmol)
      induced a 3 fold rise of ACTH release (measured by RIA) above vehicle (PBS)
      injected controls (p less than 0.001). This stimulatory effect was completely
      reversed by an i.c.v. pretreatment with the alpha 2 antagonist idazoxan (10 nmol;
      without action by itself), whereas it was only slightly affected by an i.c.v.
      pretreatment with a combination of an alpha 1 and beta blocker (prazosin +
      propranolol; 5/5 nmol; p greater than 0.1). The results strongly suggest the
      participation of alpha 2 post-synaptic receptors in the central catecholaminergic
      activation of ACTH secretion.

PMID- 1976426
TI  - Extracellular matrix: an immunological and biochemical (CAT and TOH activity)
      survey of in vitro differentiation of isolated amphibian neuroblasts.
AB  - After neural induction certain cells in the neuroepithelium immediately acquire
      the property to express certain neural phenotypes (Duprat et al., 1984, 1987).
      However, the activity of almost all the specific enzymes involved in the
      biosynthesis of neurotransmitters is considerably higher when neurectodermal
      cells are cultured with chordamesodermal cells than when they are cultured alone.
      The stimulating effects of chordamesoderm do not appear to be due to diffusible
      factors (Duprat et al., 1985b). The present study was designed to investigate the
      role of extracellular matrix components in neuronal cell differentiation. We
      showed that the extracellular matrix cannot replace chordamesoderm in stimulating
      the biochemical differentiation of neuroblasts, although fibronectin and
      especially laminin stimulate morphological differentiation. We suggest that
      interaction between neuronal and non-neuronal cells plays an important part in
      functional biochemical differentiation, whereas the molecules of extracellular
      matrix are important for morphological differentiation.

PMID- 1976427
TI  - Lack of association between two restriction fragment length polymorphisms in the
      genes for the light and heavy neurofilament proteins and Alzheimer's disease.
AB  - The etiology of Alzheimer disease (AD) remains unknown. The hypothesis of genetic
      factors playing a role in the causation of the disease, at least in its familial
      form, has been borne out by results showing linkage in several early-onset AD
      families to a locus on the proximal part of the long arm of chromosome 21.
      Linkage was not detected in several other families using the same markers. The
      metabolism of neurofilaments is perturbed in AD, as indicated by the presence of
      neurofilament epitopes in neurofibrillary tangles, as well as by the severe
      reduction of the expression of the gene for the light neurofilament subunit in AD
      brain. To detect a possible anomaly that might relate to the disease, we have
      searched for an association between the genes for the light subunit and the heavy
      subunit of the neurofilament triplet, and AD. Genotypes for restriction fragment
      length polymorphisms (RFLP) at each of the two loci were determined for an AD
      group and a control group. Allelic frequencies at a TaqI-defined RFLP for the
      gene for the light neurofilament subunit were 0.70 for the 3.7 kb allele and 0.30
      for the 2.9 kb allele. HincII detected an RFLP for the heavy neurofilament
      subunit gene with frequencies of 0.31 for the 18.0 kb allele and 0.69 for the 6.8
      kb allele. Frequencies were found to be similar in the two groups for both light
      and heavy neurofilament subunit loci. Although it cannot be excluded that
      mutations at other sites of the neurofilament genes are relevant to AD, the data
      reported here do not support an association between these genes and the disease.

PMID- 1976428
TI  - [The diagnosis of alcoholism in family medicine: a pilot study of the correlation
      of the Michigan Alcoholism Screening Test and the level of serum gamma
      glutamyltransferase].
AB  - When used simultaneously, are laboratory and psychosocial methods of screening
      helpful to detect alcoholism in general practice? To examine this issue,
      systematic screening with a self-administered Michigan Alcoholism Screening Test
      and measurement of the plasma gamma-glutamyltransferase level was offered to 435
      clients at a family medicine clinic. Whenever a positive finding was obtained the
      client was free to undergo a more detailed evaluation to confirm the diagnosis. A
      total of 200 subjects (126 women, 74 men) agreed to undergo screening. The
      results do not appear to lead to practical consequences among women, in whom no
      case was identified. In contrast, in the male population a rate of first
      detection of 9.5% (seven cases) should encourage such screening for alcoholism in
      family medicine.

PMID- 1976430
TI  - Negative symptoms in schizophrenia.

PMID- 1976429
TI  - Affect regulation and psychopathology: bridging the mind-body gap.
AB  - A failure of affect regulation is put forward as central to the development of
      psychopathology. Giving affect regulation this pivotal role allows one to explain
      how the various theories of intervention (for example, dynamic, behavioural,
      medical) can all have relatively similar results. As well, it provides an
      explanation for the common findings of brain and language dysfunction in
      psychopathology, the co-occurrence of anxiety disorders in various other mental
      disorders and the responsiveness of individuals with severe pathology to the
      affect in their environments. A model is presented linking the reticular, limbic
      and frontal systems of the brain with the conceptual frameworks used by mental
      health workers in their efforts to intervene. To illustrate how the model may be
      used, it is applied to various disorders.

PMID- 1976431
TI  - Pharmacotherapy of the borderline patient.

PMID- 1976432
TI  - No rearrangement of c-mos in salivary gland pleomorphic adenomas with 8q12
      aberrations.
AB  - The frequent occurrence of salivary gland pleomorphic adenomas characterized by
      clonal structural chromosome abnormalities involving 8q12 raises the question as
      to how the cytogenetic rearrangements correspond to molecular mechanisms of tumor
      development. Since the proto-oncogene c-mos maps to this breakpoint region, DNA
      from eight adenomas with these aberrations was isolated and checked for
      rearrangements of c-mos after digestion by BamHI, EcoRI and HindIII. In none of
      the tumors was a rearranged allele besides the germ-line fragments found.

PMID- 1976433
TI  - Philadelphia chromosome-positive chronic myelogenous leukemia in treated
      Hodgkin's disease.
AB  - A patient who developed Philadelphia (Ph) chromosome-positive chronic myelogenous
      leukemia (CML) 8 years after successful treatment for Hodgkin's disease (HD) is
      reported. The Ph chromosome with a typical 9(22) translocation was identified by
      banding techniques in 80% of bone marrow (BM) cells. Southern blot analysis
      showed breakpoint cluster region (BCR) rearrangement as observed in classical
      CML. Until now, only three cases of Ph + CML have been reported after treatment
      for HD. At present, it is not clear whether development of CML after HD
      represents a therapy-induced complication, an increased susceptibility to
      secondary malignancies owing to the malignant process itself, a consequence of
      the immunological deficiencies in HD, or possibly a genetic susceptibility to
      malignancy.

PMID- 1976434
TI  - Increased expression of c-jun gene during spontaneous hepatocarcinogenesis in LEC
      rats.
AB  - We have studied the expressions of nine proto-oncogenes (c-myc, N-myc, c-fos, C
      jun, p53, H-ras, N-ras, c-raf, hst) and two other genes (PCNA, GST-P) during the
      spontaneous development of hepatocellular carcinomas (HCCs) in LEC rats.
      Expression of c-myc, H-ras, N-ras, C-raf, p53 and PCNA genes was detected, but
      this did not significantly change during the development of HCCs in LEC rats.
      Expression of N-myc and hst genes was not detectable. Expression of c-fos gene
      was detected in one HCC case out of four. Significantly increased expression of c
      jun gene was observed in the liver tissues of LEC rats aged 8 months. This high
      expression was decreased with the development of HCCs. On the other hand, the
      expression of GST-P gene increased in parallel with the clinical course of the
      development of HCCs in LEC rats. The pattern of c-jun mRNA augmentation was
      different from that of GST-P mRNA. These observations suggest that c-jun gene may
      play a role in the spontaneous development of HCCs in LEC rats.

PMID- 1976435
TI  - Peripheral blood lymphocyte subpopulations in Indian women with cervical
      intraepithelial neoplasia and invasive cancer--an immunocytochemical study using
      monoclonal antibodies.
AB  - The peripheral blood lymphocyte subpopulations in Indian women with various
      grades of cervical intraepithelial neoplasia [33], invasive cancer [22] and
      matched controls [30] were studied using specific monoclonal antibodies and
      biotin avidin immunofluorescence technique. Our results showed a significant fall
      in peripheral T (CD2) B(CD22) cells in patients with CIN III and invasive
      cervical cancer lesions compared to controls (P less than 0.001). Similarly the
      quantum of T helper cells (CD4) decreased according to the severity of cervical
      lesions (P less than 0.01 - P less than 0.001), whereas the T suppressor cells
      (CD8) depicted an increasing trend in patients with higher grade of cervical
      lesions (CIN III and invasive cancer, P less than 0.001) as compared to controls.
      Further, the CD4/CD8 ratio showed a significant downfall with the severity of
      cervical lesions (P less than 0.01 - P less than 0.001), indicating a perturbance
      in the homeostasis of host cellular immunity.

PMID- 1976436
TI  - Loss of heterozygosity of markers on chromosome 11 in tumors from patients with
      multiple endocrine neoplasia syndrome type 1.
AB  - Multiple endocrine neoplasia type 1 is an autosomal dominant condition
      characterized by the development of parathyroid hyperplasia, pituitary adenomas,
      and pancreatic islet cell tumors. Recently the gene for multiple endocrine
      neoplasia type 1 was mapped to the long arm of chromosome 11 between the loci PGA
      and INT2. We tested the hypothesis that tumor development is the result of a
      somatic deletion that unmasks a constitutional mutation. By investigating DNA
      isolated from tumors and somatic tissues in 12 patients from 4 different families
      with multiple endocrine neoplasia type 1, we found loss of heterozygous markers
      mapped to 11q13 in 9 (82%) of 11 informative tumors. In contrast, we were unable
      to identify allelic loss from other chromosomes using a variety of informative
      probes. This high incidence of chromosomal deletion of 11q13 suggests that this
      region is important in the oncogenesis of this disorder.

PMID- 1976437
TI  - Response of mouse skin tumors to doxorubicin is dependent on carcinogen exposure.
AB  - To investigate the role of carcinogenesis in determining the response of tumors
      to anticancer drugs, we have used the in vivo model of multistage carcinogenesis
      of the mouse skin. Mice were initiated with Harvey murine sarcoma virus or single
      and repeated applications of dimethylbenzanthracene (DMBA). The papillomas which
      developed as a result of these initiation protocols were monitored quantitatively
      for their response to the anticancer drug doxorubicin. A single dose of 10 mg/kg
      doxorubicin is relatively inefficient at reducing the frequency of papillomas
      arising as a result of either single or repeated applications of the chemical
      DMBA. However, virally initiated papillomas are sensitive to the single 10-mg/kg
      dose of doxorubicin and are reduced in frequency by greater than 80%. Repeat
      treatment with four doses of 5 mg/kg doxorubicin over a 4-week period also
      reveals differences in the responses of the papillomas to doxorubicin. As with
      the single dose of doxorubicin, papillomas initiated with multiple applications
      of DMBA showed only a limited response to four 5-mg/kg doses of doxorubicin. In
      comparison both the virally initiated and the single DMBA initiated papillomas
      responded to the four doses of doxorubicin and are reduced in frequency by about
      80%. These data show that the response of papillomas to doxorubicin is related to
      the initiating event. Papillomas derived by viral initiation are most sensitive
      to doxorubicin while increasing the level of exposure to the chemical carcinogen
      DMBA increases the proportion of papillomas which do not respond to treatment
      with doxorubicin. There was no obvious relationship between the method of
      initiation or the treatment of the mice with doxorubicin and the levels of P
      glycoprotein expression observed in the papillomas. All the papillomas expressed
      detectable levels of P-glycoprotein approaching that of the multidrug resistant
      cell line, CHRC5.

PMID- 1976438
TI  - Modulatory role for CCK-B antagonists in Parkinson's disease.
AB  - We examined the ability of selective CCK-A and CCK-B receptor antagonists to
      induce or modulate the locomotor stimulant effects of dopamine agonists in MPTP
      treated squirrel monkeys. Administration of 1-100 micrograms/kg i.p. of either
      the selective CCK-A receptor antagonist devazepide (MK-329) or the CCK-B receptor
      antagonist L-365,260 alone failed to stimulate a locomotor response in
      parkinsonian monkeys. In contrast, treatment with L-365,260 caused a 50-60%
      potentiation of the locomotor stimulatory effects of L-DOPA or (+)-PHNO. No such
      modulatory effects were observed following pretreatment with devazepide. We
      suggest that CCK-B receptor antagonists may be useful adjuncts to existing
      dopamine replacement therapy for improved management of Parkinson's disease.

PMID- 1976439
TI  - [Nitric oxide--a new and nontraditional transmitter].
AB  - NO is obviously identical with the relaxation factor produced by the vascular
      endothelium (EDRF) and is also the substance responsible for some other
      biological activities. It is formed in the organism from L-arginine by the action
      of the enzyme NO synthetase. The main mechanism of action is the activation of
      the enzyme guanyl cyclase and the result is an increase of the intracellular
      level of cyclic guanyl monophosphate. Depending on the type of effector cell,
      either vasodilatation occurs and adhesion is inhibited and the blood platelets
      coagulate or the cytotoxicity of macrophages increases. With the development of
      new, more effective inhibitors of NO synthetase there is also the possibility to
      study the physiological importance of NO in more detail. These new discoveries
      provide a more profound biochemical and pharmacological basis and perhaps also
      new indications or preventive possibilities of the known treatment of vascular
      spasms by nitroderivatives; moreover, there is the possibility to seek new ways
      in the anti-tumourous and antimicrobial treatment and elsewhere.

PMID- 1976440
TI  - Inhibition by anti-CD2 monoclonal antibodies of anti-CD3-induced T cell-dependent
      B cell activation.
AB  - Anti-CD3 mAb can activate T cells to help in B cell activation as detected by
      late events, such as maturation of B cells into Ig-secreting cells (IgSC), or by
      early events, such as B cell surface expression of the activation marker CD23.
      Two different anti-CD2 mAb each inhibited anti-CD3-induced T cell-dependent B
      cell activation in a dose-dependent fashion. Neither irradiation of the T cells
      prior to culture nor depletion of CD8+ cells abrogated the inhibitory effects of
      anti-CD2 mAb. Despite the ability of these anti-CD2 mAb to inhibit anti-CD3
      induced IL2 production, addition of exogenous IL2 to anti-CD2 mAb-containing
      cultures could not fully reverse the inhibitory effects on IgSC generation.
      Furthermore, addition of various combinations of IL1, IL2, IL4, and IL6 or crude
      PBMC or monocyte culture supernatants also could not reverse anti-CD2-driven
      inhibition. In T cell-depleted cultures, anti-CD2 mAb had no effect on the
      ability of IL4 to induce B cell CD23 expression, confirming that anti-CD2 mAb had
      no direct effect on B cells. However, in cultures containing T+ non-T cells, anti
      CD2 mAb did partially inhibit IL4-induced B cell CD23 expression. Taken together,
      these observations demonstrate that certain CD2 ligands can modulate T cell
      dependent B cell activation by a mechanism which, at least in part, involves a
      direct effect by the CD2 ligand on the T cell itself.

PMID- 1976442
TI  - Potential neuroleptic agents, N-[(2-pyrrolidinyl)methyl]-2,3-dihydrobenzofuran-7
      carboxamide derivatives.
AB  - A series of 2,3-dihydrobenzofuran-7-carboxamides, presenting a stabilized
      intramolecular hydrogen bond, was synthesized and evaluated in pharmacological
      models for antipsychotic activity. Among them, N-[(1-butyl-2-pyrrolidinyl)methyl]
      2-methyl-5-sulfamoyl-2, 3-dihydrobenzofuran-7-carboxamide (15) showed an atypical
      neuroleptic profile similar to that of sulpiride (1) and more lipophilic
      properties than 1. Compound 15 was 11 times more potent in antagonistic activity
      on apomorphine-induced hyperactivity in mice (ED50 = 30 mg/kg, p.o.) and stronger
      in potentiation of methamphetamine lethality in rats than 1, while it was as weak
      in inhibitory activity of apomorphine-induced stereotype in rats (ED50 greater
      than 500 mg/kg, p.o.) as 1. On the other hand, N-[(1-ethyl-2-pyrrolidinyl)methyl]
      2-methyl-5-methylthio-2, 3-dihydrobenzofuran-7-carboxamide (30) showed a
      classical neuroleptic profile with a potency comparable to haloperidol in
      antagonistic activity on apomorphine-induced hyperactivity in mice (ED50 = 0.65
      mg/kg, p.o.). The structure-activity relationships were also discussed.

PMID- 1976441
TI  - Selection of T cell receptor expression mutants through the functionally linked
      Ly-6A.
AB  - Ly-6A is a glycosyl-phosphatidylinositol (GPI)-anchored molecule that
      participates in murine T cell activation. Activation of T cell hybridomas with
      anti-Ly-6A monoclonal antibody (mAb) leads to production of interleukin-2 (IL-2),
      but also to a paradoxical growth inhibition, which was used to select for
      signaling mutants. Fifteen subclones derived from two independent mutageneses and
      anti-Ly-6A selection were characterized. Thirteen subclones responded poorly or
      not at all to soluble anti-Ly-6A mAb. Although the selective pressure was exerted
      through Ly-6A, only one mutant did not express the Ly-6A antigen. Interestingly,
      10 of the 15 subclones expressed either nondetectable or a very low level of T
      cell receptor/CD3 complex (TCR/CD3). Preferential expansion of TCR/CD3 expression
      mutants following anti-Ly-6A selection further established functional linkage
      between Ly-6A and TCR/CD3 complex. The mechanism of the functional coupling was
      investigated by analyzing the hydrolysis of phosphatidylinositol 4,5-bisphosphate
      (PIP2), one of the early events in T cell activation. We showed that PIP2 was not
      hydrolyzed in response to anti-Ly-6A in TCR/CD3-negative mutants. Aluminum
      fluoride, which activates G protein directly, did induce PIP2 hydrolysis in these
      cells. These data suggest that activation signals originated from Ly-6A must be
      transmitted first to TCR/CD3 complex, which then couples to the G
      protein/phospholipase C system. A similar requirement also applies to the Thy-1
      protein and lectin receptors. Thus, the TCR/CD3 complex plays a central role in
      the integration and transmission of activation signals that originated from
      several T cell surface molecules.

PMID- 1976443
TI  - Structure-activity relationship of yohimbine and its related analogs in blocking
      alpha-1 and alpha-2 adrenoceptors: a comparative study of cardiovascular
      activities.
AB  - We investigated the selectivities and structure requirements for alpha-1 and
      alpha-2 adrenoceptor blocking activities of yohimbine (YO) and its 12 related
      analogs, such as beta-yohimbine (beta-YO), dihydrocorynantheine (DHC) and (
      )indoloquinolizidine ((-)IQ). The affinity of YO analogs to alpha-adrenoceptor
      was assessed by measuring their blockade of pressor responses to epinephrine in
      pithed rats. Among YO structure groups, the potency order was YO greater than DHC
      = beta-YO greater than geissoschizine methylether greater than 14 beta-hydroxy YO
      greater than 14 beta-benzoyloxy YO (inactive). (-)IQ was slightly less potent
      than YO, but much stronger than (+)IQ. Among (+/-)IQ structure groups, the
      potency order was (+/-)IQ greater than (+/-)1,12b-trans-1-hydroxy IQ much greater
      than (+/-)1,12b-cis-1-hydroxy IQ (inactive). (+/-)Borrerine was active, but (+/
      )desmethylborrerine was inactive. The alpha-1 blocking activities of the four
      compounds YO, beta-YO, DHC and (-)IQ, were assessed in experiments of pressor
      responses to methoxamine in pithed rats and contractile responses to methoxamine
      in the rat vas deferens. The potency order was (-)IQ greater than YO greater than
      DHC greater than beta-YO. Furthermore, the alpha-2 blocking activities of the
      four analogs were assessed in experiments of pressor responses to clonidine and
      inhibition of electrically driven cardioacceleration by clonidine, in pithed
      rats. The potency order was YO greater than beta-YO greater than (-)IQ greater
      than DHC. Based on the potency ratio between alpha-1 and alpha-2 blocking
      activities, DHC or YO was most selective for alpha-1 or alpha-2 subtype,
      respectively, among the four YO analogs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1976444
TI  - A large-scale synthesis of [MeTyr1, MeArg7, D-Leu8]dynorphin A-(1-8)-NHEt (E
      2078) by application of the trifluoroacetic acid-pentamethylbenzene deprotecting
      procedure in the final stage.

PMID- 1976445
TI  - [Nursing care of patients treated with monoclonal antibody in intractable renal
      homograft rejection].

PMID- 1976446
TI  - [Cell-mediated immunity in chronic pyelonephritis].
AB  - The authors used monoclonal antibody (CD3, CD4, CD8) and indirect
      immunofluorescence technic to study peripheral blood lymphocyte surface markers
      in patients with chronic pyelonephritis (CPN) and in normal controls. In CPN
      patients, a significant decrease in CD3, a lower percentage of CD4 and
      significant higher percentage of CD8 leading to a decrease in the CD4/CD8 ratio
      were noted. No differences could be observed between Spleen-Kidney Yang
      deficiency and Kidney Yin deficiency. The overall picture shown by the CPN
      patients was compatible to a cell-mediated immune response defection. The CPN
      patients were then treated with Zi-Ling capsule (ZLC)/transfer factor (TF) and
      various antibiotics for three months, during which period the authors found a
      significant increase in CD3, CD4, but no significant change in CD8. Symptoms such
      as lumbago, fatigue, frequency of urination were improved. A significant
      decreased in CD4 after cessation of treatment with ZLC and TF was observed. These
      observations suggested that both ZLC and TF could also improve the immune
      function, however, they mainly affect CD4 but not CD8 cells, and the effect
      lasted for only a short period. In conclusion, ZLC/TF and antibiotics
      administered together would serve as a useful therapeutic measure to be
      recommended for patients with CPN.

PMID- 1976447
TI  - [Evaluation of larvicide susceptibility of Culicidae in French Polynesia].
AB  - Larval tests on 4th-stage Aedes aegypti, Aedes polynesiensis and Culex
      quinquefasciatus of French Polynesia, according to the WHO method, demonstrate
      susceptibility of these species to organophosphorous compounds and less
      susceptibility to insect growth regulators.

PMID- 1976449
TI  - Clinical, electrical and mechanical correlations during recovery from
      neuromuscular blockade with vecuronium.

PMID- 1976448
TI  - Pancuronium, vecuronium, and d-tubocurarine inhibit and succinylcholine
      stimulates choline acetyltransferase activity.
AB  - The effects of the nondepolarizing muscle relaxants (NDMR), pancuronium,
      vecuronium, and d-tubocurarine and a depolarizing muscle relaxant,
      succinylcholine, were studied on choline acetyltransferase (ChAT) activity. A
      radiochemical assay was used in the determination of ChAT activity using purified
      placental enzyme. Pancuronium at concentrations of 10(-7) M, 10(-6) M, 10(-5) M,
      10(-4) M, and 10(-3) M inhibited ChAT activity by 3, 10, 15, 40 and 85 per cent,
      respectively; vecuronium at concentrations of 10(-6) M, 10(-5) M, 10(-4) M, and
      10(-3) M inhibited ChAT activity by 5, 10, 26 and 57 per cent, respectively; d
      tubocurarine at concentrations of 10(-6) M, 10(-5) M, 10(-4) M, and 10(-3) M
      inhibited ChAT activity by 0, 4, 12.5 and 29 per cent, respectively; whereas
      succinylcholine at concentrations of 10(-7) M, 10(-6) M, 10(-5) M, and 10(-4) M
      activated ChAT activity by 8, 10, 1, and 2 per cent, respectively. Even though
      our present data demonstrated a significant dose-dependent inhibitory effect on
      ChAT activity by pancuronium, vecuronium and d-tubocurarine, it is unlikely that
      this inhibitory effect will contribute to the mechanism of action of NDMR. Our
      data, however, may suggest an additional mechanism for the phenomena of tetanic
      and train-of-four fades that are seen following the administration of
      nondepolarizing muscle relaxants.

PMID- 1976450
TI  - Characterization of an etoposide-resistant human small-cell lung cancer cell
      line.
AB  - We established an etoposide (VP-16)-resistant human small-cell lung cancer cell
      line (H69/VP) by stepwise exposure to VP-16. The resistance of H69/VP to VP-16
      was 9.4-fold that of the parent cell line (H69/P). H69/VP showed cross-resistance
      to Adriamycin (ADM), (4S)-4,11-diethyl-4-hydroxy-9-[(4-piperidinopiperidino)
      carbonyloxy]-1H-pyrano[3',4':6,7]indolizino [1,2-b]quinoline-3,14(4H,12H)
      dionehydrochloride trihydrate (CPT-11), teniposide (VM-26), vindesine (VDS) and
      vincristine (VCR). The amount of DNA topoisomerase II (topo.II) was nearly the
      same in H69/P and H69/VP cells. The catalytic activity of topo.II in H69/VP cells
      was lower than that in the H69/P line. Accumulation of [3H]-VP-16 in H69/VP was
      6.1-7.5 times lower than that in H69/P. According to Northern blot analysis, the
      mdr-1 mRNA level in H69/VP was markedly higher than that in H69/P. These findings
      suggest that H69/VP has a typical multidrug resistance (MDR) phenotype and that
      alteration of the drug accumulation mediated by P-glycoprotein may play an
      important role in resistance to VP-16. Reduced topo.II activity may also be
      associated with VP-16 resistance.

PMID- 1976451
TI  - Mitomycin C cross-resistance induced by adriamycin in human ovarian cancer cells
      in vitro.
AB  - We prepared Adriamycin-resistant cancer cells by exposing an ovarian serous
      cystadenocarcinoma cell line to the drug. The resistant cells also showed cross
      resistance to a wide variety of other compounds, including vincristine,
      vinblastine, actinomycin D, daunorubicin, mitomycin C and carboquone. Against
      vincristine, the cells showed a greater than 5,000-fold increase in resistance,
      far surpassing their resistance to the selection drug. The resistant cells
      displayed a decrease in intracellular Adriamycin content and an increase in the
      mRNA of the mdr-1 gene coding for P-glycoprotein, with no amplification of the
      DNA. In revertant cells, resistance to Adriamycin was lost, but that to mitomycin
      C was maintained. Adriamycin resistance was partially overcome by the addition of
      verapamil or cyclosporin A, but cross-resistance to mitomycin C was not
      influenced at all. These results strongly suggest that the resistance to
      mitomycin C observed in our Adriamycin-resistant cells was due to some other
      mechanism than that causing multidrug resistance.

PMID- 1976453
TI  - Analysis of pulmonary vascular responses in cats to sympathetic nerve stimulation
      under elevated tone conditions. Evidence that neuronally released norepinephrine
      acts on alpha 1-, alpha 2-, and beta 2-adrenoceptors.
AB  - The influence of an increase in vascular tone on responses to sympathetic nerve
      stimulation and the receptors mediating these responses were investigated in the
      pulmonary vascular bed of the cat. Under conditions of controlled blood flow and
      constant left atrial pressure, stimulation of the sympathetic nerves to the lung
      elicited a biphasic response characterized by an initial increase in lobar
      arterial pressure followed closely by a decrease. The response to nerve
      stimulation was reproducible with respect to time and was not altered when a
      delay coil was added to the perfusion circuit, indicating that the response was
      directly mediated. The increase in pressure was reduced by prazosin and by
      yohimbine, whereas the decrease in pressure was blocked by propranolol or ICI
      118551. These data suggest that the pressor component of the response is mediated
      by alpha 1- and postjunctional alpha 2-adrenoceptors, whereas the depressor
      response is mediated by beta 2-receptors. The pressor response was enhanced by
      propranolol or ICI 118551, whereas the depressor response was enhanced by
      prazosin or yohimbine, suggesting that the response to nerve stimulation
      represents the net effect of the actions of neuronally released norepinephrine on
      alpha- and beta-receptors. The pressor response to nerve stimulation was enhanced
      when tone was elevated with a prostaglandin endoperoxide analogue and when beta
      receptors were blocked. The effects of an increase in tone and a passive increase
      in pressure on responses to sympathetic nerve stimulation were
      different.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1976452
TI  - Pulmonary edema induced by phagocytosing neutrophils. Protective effect of
      monoclonal antibody against phagocyte CD18 integrin.
AB  - We studied the changes in pulmonary hemodynamics and lung wet weight induced with
      opsonized zymosan (OZ) in isolated guinea pig lungs perfused with Ringer-albumin
      solution containing neutrophils (PMNs). Addition of OZ to the PMN-perfused lungs
      caused pulmonary vasoconstriction and weight gain; neither OZ nor PMNs added
      individually to the perfusate altered pulmonary vasomotor tone or wet weight. The
      steady gain in lung weight by 1,588 +/- 464 mg over the 45-minute study period
      was associated with pulmonary capillary hypertension and an increase in the
      capillary filtration coefficient, indicative of increased lung vascular
      permeability. These responses may not be due to generation of oxygen radicals,
      because the alterations in pulmonary hemodynamics and lung weight were not
      reduced by addition of superoxide dismutase, catalase, or superoxide dismutase
      plus catalase. We examined the basis of the PMN-mediated effects by layering PMNs
      on bovine pulmonary artery endothelial monolayers. Challenge with OZ resulted in
      increased endothelial permeability to 125I-albumin. The monoclonal antibody IB4
      (directed against CD18, the common beta-subunit of structurally related adhesion
      receptors on phagocytes, LFA-1, Mac-1, and P150,95) prevented the OZ-mediated
      increase in PMN adherence to endothelial cells and the increase in endothelial
      permeability to 125I-albumin. IB4 also inhibited the lung weight gain mediated by
      the OZ-stimulated PMNs in intact lungs. The protective effect of IB4 could be
      ascribed neither to inhibition of uptake of OZ by PMNs nor to inhibition of
      release of oxygen radicals, myeloperoxidase, and elastase.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1976454
TI  - Emergence and development of immunoreactive cells in teleostean retinas during
      the perinatal period.
AB  - We have used light-microscopical immunohistochemistry to investigate
      developmental changes of several neurochemical indicators in retinas of perinatal
      killifish and goldfish. Immunoreactive proliferating cell nuclear antigen (ir
      PCNA/cyclin, a marker for replicating cells) was present in nuclei of all
      neuroblasts in the early monolayer stage, but was lost progressively in central
      to-peripheral and proximal-to-distal order as the layers and cells of the mature
      retina appeared. The loss of ir-PCNA was slightly prior to the appearance of ir
      TH (tyrosine hydroxylase), GAD (glutamic acid decarboxylase) and GS (glutamine
      synthetase) at the 4th embryonic day (E4) in both fish. Since hatching was
      earlier in goldfish (E5) than in killifish (E7), neurochemical maturation was
      evident at 2-3 days before hatching in killifish but not until around hatching in
      goldfish. Two markers, ir-somatostatin and protein kinase C, were detected by the
      1st postnatal day (H1) in goldfish, but not in perinatal or adult killifish
      retinas. Thus the course of development of killifish and goldfish retinas is
      similar, but not identical. The validity of ir-PCNA as a marker for proliferating
      cells is confirmed by the coincidence of its disappearance with the appearance of
      neurochemical markers for mature, postmitotic retinal cells.

PMID- 1976455
TI  - Laboratory integration: robotics and automation. Twenty-second annual Oak Ridge
      Conference on Advanced Concepts for the Clinical Laboratory. Proceedings.

PMID- 1976457
TI  - Clearance of different multiple forms of human gamma-glutamyltransferase.
AB  - Several multiple forms of gamma-glutamyltransferase (EC 2.3.2.2) have been
      described in serum. Most of these are large complexes between the enzyme and
      circulating lipoproteins. One dominating form is complexed with high-density
      lipoprotein; a small, hydrophilic form is present in minor amounts. We purified
      the two forms by immunoaffinity chromatography, injected the purified forms into
      rabbits, and studied the clearance of the two forms by measuring the change in
      enzyme activity and in enzyme protein concentration with an enzyme-linked
      immunosorbent assay. The half-life of the hydrophilic enzyme was 9 h; that of the
      lipoprotein-enzyme complex was 20 h. This indicates that the lipoprotein-enzyme
      complex accumulates in serum relative to the hydrophilic enzyme, suggesting in
      part an explanation of the dominance of the larger form in disease.

PMID- 1976456
TI  - Characterization and rapid diagnostic analysis of DNA polymorphisms closely
      linked to the cystic fibrosis locus.
AB  - Six genetic polymorphisms, closely linked to the cystic fibrosis gene and useful
      in clinical linkage analysis, have been characterized and converted to a more
      rapid form of assay. Sequences flanking the metD (Ban I), metH (Msp I), XV-2c
      (Taq I), KM.19 (Pst I), MP6d-9 (Msp I), and J3.11 (Msp I) polymorphic restriction
      sites have been determined and used to design specific polymerase chain reaction
      (PCR) amplification primers and allele-specific oligonucleotide probes. All six
      of these polymorphisms were found to involve single-base alterations, and the XV
      2c polymorphism was found to lie within an Alu repeat segment. These PCR-based
      tests, in conjunction with the CS.7 (Hha I) assay described elsewhere (Stanier P
      et al. Hum Genet 1988;80:309-10; Williams C et al. Lancet 1988;ii:102-3), provide
      a convenient, rapid, and reliable method of haplotype and linkage analysis,
      clinically useful in those situations where direct detection of mutations is not
      possible.

PMID- 1976458
TI  - Urinary adenosine deaminase binding protein, a marker of contrast media induced
      acute renal damage.

PMID- 1976459
TI  - Heart-hand syndrome II. A report of Tabatznik syndrome with new findings.
AB  - The association of upper limb malformations and congenital cardiac anomalies was
      established as a definite clinical and genetic entity by Holt & Oram in 1960.
      Significant variability of malformations in both the upper limbs and the
      cardiovascular system has been well documented. In 1978, Temtamy & McKusick
      reported a family studied by Tabatznik, in which upper limb deformities,
      including type D brachydactyly, occurred in association with cardiac arrhythmias
      as a dominant, either autosomal or X-linked trait. They called this apparently
      new entity "Heart-Hand syndrome II" to distinguish it from the Holt-Oram
      syndrome. No other similar cases have subsequently been reported. We describe
      here the second family affected with the Tabatznik syndrome and add some new
      findings to the clinical spectrum of this condition.

PMID- 1976460
TI  - Exclusion mapping of 12 X-linked disease loci and 10 DNA probes from the long arm
      of the X-chromosome.
AB  - Specific chromosome rearrangements associated with disease entities are
      invaluable resources for physical mapping. A deletion on the X chromosome of a
      male leads to the nullisomy for X-linked genes, resulting in the onset of genetic
      diseases and/or the absence of the DNA probe detectable sequences. This permits
      the localization of these loci within the deleted area. On the other hand, the
      region for some other X-linked loci can be excluded from the deleted area
      according to the absence of the characteristic symptoms of the disease and/or the
      presence of the hybridization signals. An interstitial deletion on the long arm
      of the X chromosome of a male has been characterized by high resolution banding.
      The karyotype of the proband is 46,Y,del(X)(pter----q21.1::q21.33----qter). The
      regions for 12 X-linked disease loci as well as 10 DNA probes are excluded from
      the deleted area, and localized either proximally or distally to the deletion.
      The results also reveal a controversy in the present linkage data concerning the
      assignment of these loci.

PMID- 1976461
TI  - Reduced oxidative burst responses in monocytes and monocyte-derived macrophages
      from HIV-infected subjects.
AB  - Oxidative burst responses of monocytes and monocyte-derived macrophages (MDM)
      were studied in 40 subjects with HIV infection of different clinical stages.
      Oxidative burst was assessed as reduction of nitroblue tetrazolium (NBT) with or
      without stimulants. Results were determined as oxidative burst responses per cell
      and as a stimulatory ratio between stimulated and unstimulated NBT reduction.
      Cells from 12 HIV-seronegative homosexual men and 38 blood donors served as
      control groups. In patients with asymptomatic HIV infection, monocyte oxidative
      burst responses were reduced compared with the blood donors. In MDM from the same
      patients, stimulatory ratios were reduced. In AIDS patients, stimulatory ratios
      of both monocytes and MDM were reduced compared with controls. In contrast to the
      progressive deterioration of CD4+ lymphocyte counts as well as other immune
      functions in HIV infection, monocyte oxidative burst responses are impaired
      already in the asymptomatic phase of the infection, almost to the same extent as
      in patients with AIDS.

PMID- 1976462
TI  - Activation of lymphocytes after platelet allotransfusion possessing only class I
      MHC product.
AB  - After platelet allotransfusion, we found a characteristic increase in the
      expression of interleukin-2 receptor, dipeptydilpeptidase IV (CD26), activation
      inducer molecule (AIM, CD69) and transferrin receptors (CD71) on day 3 indicating
      that important functional molecules expressed on the activation of lymphocytes by
      allogeneic platelets. At the same time, no consistent increase of other
      activation molecules such as Ki-l (CD30), intercellular adhesion molecule (ICAM
      1, CD54) and Ki-24 (CDw70) antigen expression was detected, probably as a result
      of the selective activation of some lymphocyte subsets. In order to obtain
      further evidence for the in vivo activation triggered by allogeneic platelets,
      subsequent step of T cell activation towards differentiation was investigated
      with monoclonal antibodies to leucocyte common antigens. A sharp expression of
      the UCHL1, coupled with a decrease of the CD45R molecule was detected on day 7 or
      14, suggesting a T cell priming.

PMID- 1976463
TI  - Signal requirements for activation of leukaemic T cells from a chronic
      lymphocytic leukaemia (T-CLL).
AB  - In order to define the signal requirements for leukaemic T cell activation, the
      proliferation and interleukin-2 (IL-2) production of peripheral lymphocytes from
      a patient with a HTLV-I-, CD4+, CD45RA+ CD45RO+ CD25- T-CLL were evaluated after
      the delivery of different stimuli. Unlike resting CD4+ normal T lymphocytes that
      can be activated only by a two-signal stimulation, T-CLL cells proliferated and
      released IL-2 in response to a pair of anti-CD2 monoclonal antibodies (MoAbs) or
      concanavalin A (Con A) in the absence of both accessory cells (AC) and phorbol
      myristate acetate (PMA). The two stimuli were also able to induce CD25 expression
      within 12-20 h on the majority of T-CLL cells. A response to anti-CD3 and anti
      CD28 MoAbs was detected only in the presence of PMA, similar to that observed in
      normal resting T lymphocytes matched for phenotype. Both Con A- and CD2-induced
      proliferation were strongly inhibited by the addition of anti-CD25 MoAb.
      Furthermore, T-CLL lymphocytes acquired anti-tumour lytic activity after culture
      in the presence of PMA and ionomycin. We conclude that HTLV1- CD25- T-CLL can be
      characterized not only by morphological and phenotypical studies but also on the
      basis of signal requirements for cell activation.

PMID- 1976465
TI  - The GISSI-2 trial: premises, results, epidemiological (and other) implications.
      Gruppo Italiano per lo Studio delia Sopravvivenza nell'Infarto Miocardico.
AB  - Population trials on myocardial infarction have produced significant advances in
      therapeutic results. The first clearly stated aim of the GISSI-2 protocol was the
      assessment of the overall benefit to a population attributable to the application
      of a package of pharmacological treatments (thrombolysis, intravenous beta
      blockade, and oral aspirin) shown effective in reducing mortality in large-scale
      randomized clinical trials. At variance with the classical concept of trials, a
      clinical epidemiological interest came first: The comparison between drugs was
      considered a main target of the investigation only within that broader framework,
      and was explicitly formulated as the direct confrontation between two concepts or
      two generations of thrombolysis. A selective, highly efficient, and specific new
      thrombolytic agent, tissue plasminogen activator (tPA), is compared with
      streptokinase with the expectation that the more selective approach could enhance
      the benefits of specificity, drastically limiting the systemic risks aspects
      (hemorrhagic complications). The main results of GISSI-2 are summarized. GISSI-2
      may be considered a reliable window on the epidemiology of AMI in a whole
      country. There are implications for the transfer of these clinical findings into
      public health applications and for the choice of future research priorities.

PMID- 1976464
TI  - In vitro production of interferon-gamma by peripheral blood from patients with
      Graves' disease, Hashimoto's thyroiditis and rheumatoid arthritis.
AB  - The production of interferon-gamma (IFN-gamma) by peripheral blood mononuclear
      cells (PBMC), CD4 cells, or CD8 cells in response to interleukin-2 (IL-2)
      stimulation has been studied; the samples were obtained from 12 healthy control
      subjects, 19 patients with Graves' disease (10 hyperthyroid and nine euthyroid),
      13 patients with Hashimoto's thyroiditis (four hypothyroid and nine euthyroid),
      and 15 patients with rheumatoid arthritis (11 active and four inactive). A dose
      of IL-2 (25 U/ml) was utilized to induce IFN-gamma by PBMC from all four groups.
      The incremental increase in IFN-gamma values (with IL-2 stimulation minus without
      stimulation) was significantly less in PBMC from patients with Graves' disease,
      Hashimoto's thyroiditis, and rheumatoid arthritis than that in PBMC from control
      subjects. The values from PBMC in patients with Graves' disease in a euthyroid
      state were below normal but greater than those from patients with Graves' disease
      in a hyperthyroid state. The incremental increase in IFN-gamma values from
      Graves' disease PBMC correlated with the serum TSH values (r = 0.622, P less than
      0.01), but not with thyroid autoantibodies (anti-thyroid microsomal antibodies,
      anti-thyroid microsomal antibodies, nor TSH-binding inhibitory immunoglobulin
      activities). The incremental increase in IFN-gamma from PBMC from both control
      subjects and Graves' disease was correlated with that from CD4 cells (r = 0.711,
      P less than 0.01), but not with that from CD8 cells. The production of IFN-gamma
      in response to IL-2 from PBMC in Graves' disease correlated inversely with
      thyroid function, appearing to reflect the very effect of hyperthyroidism in this
      process. The precise explanation of these phenomena remains unclear. The
      decreased response of IFN-gamma to IL-2 stimulation by PBMC from patients with
      Graves' disease, Hashimoto's thyroiditis, and rheumatoid arthritis seems to be a
      non-specific phenomenon occurring in both organ specific autoimmune disease and
      systemic autoimmune disease. It may be due to a down-regulation in autoimmune
      disease of CD4 cells in response to IL-2, a decreased level of IL-2 cellular
      receptors or a decreased receptor affinity, associated increased soluble IL-2
      receptors, or a defect of the intra-CD4 cellular IL-2 signal to produce or
      release IFN-gamma in the conditions studied.

PMID- 1976467
TI  - The incidence and patterns of pulmonary artery involvement in Takayasu's
      arteritis.
AB  - The pulmonary arterial anatomy in 44 patients with Takayasu's arteritis was
      examined by intravenous digital subtraction angiography (IV-DSA) on an outpatient
      basis using centrally delivered, small-volume, bolus injections of an ionic,
      water soluble contrast medium. Diagnostic pulmonary angiograms were obtained in
      42 patients (95.4%) without complication. Angiographically evident pulmonary
      arterial involvement was seen in six patients (14.3%). The pulmonary involvement
      was not suspected clinically in any patient and the chest radiographs were
      abnormal in only two patients (33%). The angiographic spectrum of systemic
      arterial involvement was the same irrespective of the presence or absence of
      pulmonary arterial involvement. The pulmonary arterial pressures were measured in
      two patients with abnormal pulmonary angiograms and were found normal. Follow up
      IV-DSA in one of these patients 16 months after immuno-suppressive therapy showed
      no change in the pulmonary angiographic picture.

PMID- 1976466
TI  - Myocardial energetics in dilated cardiomyopathy.
AB  - To assess hemodynamic and energetic effects of different drug interventions on
      idiopathic dilated cardiomyopathy (IDCM), we determined hemodynamic variables of
      myocardial oxygen consumption (MVO2) in 37 patients with IDCM. Hemodynamics were
      measured during routine left and right heart catheterization. MVO2 was analyzed
      from myocardial blood flow (measured by the argon method) and aortocoronary sinus
      blood oxygen difference. The hemodynamic variable which correlated best with MVO2
      was shown to be the systolic stress time integral (STI). Four different
      representative compounds were tested with respect to their acute effects on
      myocardial energetics (MVO2/STI) in patients with IDCM who were in compensated
      heart failure (NYHA class II-III). The drug interventions were performed at rest.
      Intravenous injection of the vasodilator nitroprusside yielded a 35% reduction in
      STI and a 30% reduction in MVO2; in other words, the ratio MVO2/STI was not
      altered. Injection of the calcium sensitizer and phosphodiesterase inhibitor
      pimobendan also did not alter this ratio, as both STI (36%) and MVO2 (33%) were
      lowered. The profound reduction in STI (60%) seen with the phosphodiesterase
      inhibitor enoximone was accompanied by a much smaller decrease in MVO2 (19%);
      therefore, the ratio of MVO2/STI increased significantly. An increase of this
      ratio was also seen with the partial beta-1 receptor agonist xamoterol. However,
      in this case STI did not change, whereas MVO2 increased by 26%. In summary,
      vasodilation has energy-saving effects, whereas positive inotropism is an energy
      consuming process. We conclude that the overall effect on myocardial energetics
      of a drug which possesses both positive inotropic and vasodilating properties
      depends on the balance of the two properties.

PMID- 1976468
TI  - The association between aneurysm formation and systemic hypertension in
      Takayasu's arteritis.
AB  - We have studied the incidence and patterns of aneurysm formation in 88
      consecutive patients with Takayasu's arteritis by utilizing digital subtraction
      pan-aortoarteriography by the intravenous and/or intra-arterial route. Seventy
      two patients underwent initial intravenous angiography of which 64 (89%) were
      diagnostic. All the intra-arterial studies (n = 24) were diagnostically adequate.
      Arterial aneurysms were seen in eight patients (9.1%) and the saccular variety
      (75%) was the most common. Clinical and angiographic features of these eight
      patients were compared with those of the remaining patients. No major differences
      were observed except that longstanding uncontrolled hypertension was present in
      all patients with aneurysm formation. In comparison, hypertension was observed in
      30 (49.2%) of the remaining 61 patients in whom clinical details were available.
      Angiographic localization of the aneurysm is important since there are no
      clinical features that distinguish these patients and rupture of a strategically
      located aneurysm can prove fatal. The association between hypertension and
      aneurysm formation suggests that hypertension in these patients should be
      aggressively managed at the onset of disease. In this regard percutaneous
      transluminal renal angioplasty may prove a possible management adjunct.

PMID- 1976469
TI  - Repeated exposures to cold and the relationship between skin and core
      temperatures in control of metabolic rate in the goat (Capra hircus).
AB  - 1. After 10-12 experiments in each of three goats, in which skin or core
      temperatures were lowered while the other temperatures remained sufficiently high
      to prevent metabolic rate from increasing, the core temperature threshold of
      shivering was lowered by 0.35 degrees C. 2. After 10-15 experiments, in which
      skin and core temperatures were simultaneously lowered to induce major increases
      of metabolic rate, no further change of threshold was observed, while the slope
      of metabolic rate over core temperature was reduced. 3. It is concluded that
      repeated cold exposures without manifest shivering can induce tolerance
      adaptation to cold.

PMID- 1976470
TI  - Sex differences in voluntary locomotor activity of food-restricted and ad libitum
      fed rats. Implications for the maintenance of a body weight set-point.
AB  - 1. Male and female Wistar-strain rats were studied under either ad libitum or 23
      hour food restriction conditions both with and without access to a running wheel.
      2. Daily measures were taken of body weight, food consumption and wheel
      revolutions. 3. It was observed that food restriction was associated with
      decreased food consumption and body weight but increased wheel revolutions. 4.
      Irrespective of feeding regime, females exhibited higher running rates than
      males.

PMID- 1976471
TI  - The entrainment of breathing rhythm to stride frequency in the dik-dik antelope
      (Rhynchotragus kirki) with observations on the thermoregulatory consequences.
AB  - 1. Three adult dik-dik antelopes with an average weight of 4.5 kg were used to
      investigate the rate of oxygen consumption (VO2) during exercise and the
      entrainment of respiratory rate with stride frequencies at running velocities
      between 2-11 km/hr. 2. The results of VO2 and the metabolic cost of horizontal
      locomotion were found to agree with what would be expected of an animal of this
      size. 3. Respiratory frequencies recorded during the most strenuous exercise were
      approximately 50% below the value observed when dik-diks are exposed to an
      ambient temperature (Ta) of 42 degrees C. 4. Respiratory evaporative heat loss
      was estimated to account for only 4% of the total heat production during
      exercise. 5. Respiratory frequencies were found to be entrained quite strongly to
      stride frequencies. The thermoregulatory consequences of this entrainment is
      discussed.

PMID- 1976472
TI  - Effects of temperature on the immobilization and the initiation of motility of
      spermatozoa in the male reproductive tract of the domestic fowl, Gallus
      domesticus.
AB  - 1. The motility of undiluted fowl spermatozoa taken from testis, epididymis and
      ductus deferens was negligible at 40 degrees C, around the normal avian body
      temperature. 2. The immobilization was not permanent and motility was restored by
      decreasing the temperature to 30 degrees C or by suspending in a NaCl/TES buffer
      with 2 mM Ca2+, 2 mM HCO3- or 10% seminal plasma at 40 degrees C. 3.
      Demembranated spermatozoa taken from testis, epididymis and ductus deferens were
      also immotile at 40 degrees C. However, these spermatozoa were restored the
      motility at 30 degrees C except testicular spermatozoa. 4. These results suggest
      that the capacity of movement of fowl spermatozoa can be readily obtained from
      testis, but that these spermatozoa are immotile due to temperature-dependent
      immobilization in the male reproductive tract. 5. Furthermore, it is possible
      that changes in environmental temperature at ejaculation are one of the important
      exogenous physiological factors of the initiation of fowl sperm motility.

PMID- 1976473
TI  - Comparative developmental physiology and molecular cytology of the polytrophic
      ovarian follicles of the blowfly Sarcophaga bullata and the fruitfly Drosophila
      melanogaster.
AB  - 1. The ovarian follicles of Sarcophaga and Drosophila consist of one oocyte and
      15 nurse cells, the whole being surrounded by follicle cells. Although oocyte and
      nurse cells are genetically identical sibling cells, and although they are
      interconnected by cytoplasmic bridges, their physiology is very different. 2. The
      DNA content of the oocyte nucleus (germinal vesicle) never exceeds 4C, while
      values of polyploidisation up to 1024C have been measured in the nurse cells,
      this being dependent on their position within a follicle. 3. The nurse cell
      nuclei very actively synthesize RNA, while the germinal vesicle is almost
      completely inactive in this respect. 4. It has been possible to visualise the
      major cytoskeletal elements in the different ovarian cell types. Cellular markers
      of polarity and dorsoventral asymmetry have been described. 5.
      Electrophysiological measurements have been performed to find out whether or not
      the self-electrophoresis principle may be involved in polarised transport between
      nurse cells and oocyte. 6. Most of the vitellogenin is synthesized by the fat
      body but some follicle cells also synthesize small amounts. 7. The role of 20-OH
      ecdysone in the induction of vitellogenin synthesis in the fat body, as well as
      the presence of met-enkephalin like immunoreactivity in the gonads is well
      established in both species. Not so clear is the exact role of juvenile hormones
      and the nature of brain factors controlling ovarian development. 8. Drosophila
      has the advantage of its well documented genetics while the larger species
      Sarcophaga is preferable for the study of (electro-) physiological and cell
      biological mechanisms.

PMID- 1976474
TI  - Comparative investigation of vitamins and their analogues on terminal
      differentiation, from preadipocytes to adipocytes, of 3T3-L1 cells.
AB  - 1. The effects of 20 kinds of vitamins or their analogues on the growth rate of
      preadipocytes and the terminal differentiation of preadipocytes to adipocytes was
      systematically compared in 3T3-L1 cells. 2. The addition of vitamin C markedly
      increased the growth rate of preadipocytes at over 50 microM. 3. The addition of
      vitamin K3 slowed down the growth rate at over 0.1 microM. 4. In water soluble
      vitamins and their analogues tested, the vitamin B6 group and vitamin C
      significantly stimulated the differentiation, and consequently increased the
      glycerophosphate dehydrogenase activity and triglyceride accumulation, to a
      concentration of over 10 microM. 5. Many fat soluble vitamins and their analogues
      (the vitamin A group, including beta-carotene, the vitamin D group, vitamin E and
      the vitamin K group) strongly inhibited the adipose conversion of 3T3-L1 cells at
      microM level.

PMID- 1976475
TI  - Effects of cysteamine administration on plasma concentration of metabolites,
      pancreatic glucagon and insulin in the chicken.
AB  - 1. The effects of subcutaneous injection of cysteamine (2-mercaptoethylamine, 300
      mg/kg) were investigated in 5-6 week-old chickens. 2. In the short term (1 hr),
      cysteamine increased plasma levels of glucose, free fatty acids and insulin, and
      decreased that of alpha-amino non protein nitrogen. 3. In a longer term (17-24
      hr), cysteamine increased the plasma level of glucose, did not modify those of
      alpha-amino non protein nitrogen, insulin and glucagon and decreased that of free
      fatty acids. 4. The disposal of an oral glucose load was impaired and the glucose
      induced inhibition of pancreatic glucagon and stimulation of insulin release were
      blunted 17 hr after cysteamine administration. 5. Therefore, cysteamine exerts
      multiple effects on chicken pancreatic islet cells.

PMID- 1976476
TI  - Plasma vitamin D metabolite levels in pregnant and nonpregnant ewes.
AB  - 1. Maternal calcium homeostasis during pregnancy is strained due to fetal mineral
      requirements for bone formation. 2. In most species, the mother adjusts to the
      mineral requirements of the fetus with alterations in her metabolism of vitamin D
      that include a decrease in plasma 25-(OH)D levels and an increase in circulating
      levels of the hormone, 1,25-(OH)2D. 3. Plasma 25-(OH)D and 1,25-(OH)2D levels in
      adult male, adult female and pregnant sheep were measured by specific
      radioreceptor binding assays. 4. Pregnancy did not alter circulating levels of 25
      (OH)D or 1,25-(OH)2D in the sheep. 5. The pregnant ewe differs from all species
      studied to date in that maternal plasma 1,25-(OH)2D levels do not rise as a
      result of pregnancy.

PMID- 1976478
TI  - Visual units in the central nervous system of the frog.

PMID- 1976477
TI  - Digesta retention and fibre digestion in brushtail possums, ringtail possums and
      rabbits.
AB  - 1. Mean retention times (MRTs) of fluid (marked with Co-EDTA), fine particles
      (mordanted with Yb) and large particles (mordanted with Cr) were measured in
      brushtail possums (Trichosurus vulpecula), ringtail possums (Pseudocheirus
      peregrinus) and laboratory rabbits fed semipurified diets. 2. In brushtail
      possums there were no significant differences in MRT among the three digesta
      markers. 3. In ringtail possums MRTs of the fluid and fine particle markers were
      approximately twice that of the large particle marker, indicative of selective
      retention of both fluid and fine particles in the caecum. 4. In the rabbit MRT of
      fine particles was also greater than that of large particles, again indicative of
      selective retention of fine particles in the caecum. 5. Fibre digestibility was
      greater in the rabbits than in the ringtail possums, and greater for neutral
      detergent fibre (including agar) but less for acid-detergent fibre in the rabbits
      than in the brushtails. Differences in fibre digestibility between brushtails and
      rabbits were explained by differences in patterns of digesta flow. However, the
      higher digestibilities of fibre in the rabbits than in the ringtail possums could
      not be explained on a similar basis.

PMID- 1976479
TI  - Effect of bacterial pyrogen on three lizard species.
AB  - 1. Three lizard species (Callopistes maculatus, Gerrhosaurus major, and Varanus
      exanthematicus) were tested for their response to intraperitoneal injection of
      alcohol-killed Aeromonas sobria. 2. A paired experimental design, in which each
      animal received an injection of sterile saline and 1 x 10(10) A. sobria, was
      utilized. 3. C. maculatus demonstrated a statistically significant increase in
      mean selected body temperature (MSBT) after bacteria injection. 4. G. major and
      V. exanthematicus did not demonstrate a statistically significant increase in
      MSBT. 5. C. maculatus is the first lizard species outside of the family Iguanidae
      to exhibit a febrile response to bacterial pyrogen.

PMID- 1976480
TI  - Staircase potentiation in isolated frog skeletal muscle: power spectral analysis
      of the evoked compound muscle action potential.
AB  - 1. The mechanical and electrophysiological effects of repetitive, low-frequency
      electrical stimulation on paired sartorii muscles from small male frogs have been
      investigated, in vitro. 2. Stimulation for 90 sec at 5 Hz resulted in a
      progressive rise (staircase) than fall (fatigue) in peak twitch tension. 3. The
      root mean square amplitude, peak-to-peak amplitude, conduction velocity and mean
      power frequency of evoked compound muscle action potentials (CMAPs) decreased
      over the stimulation period. 4. Results suggest that alterations in the shape of
      the CMAP during repetitive stimulation may contribute to the staircase
      phenomenon.

PMID- 1976481
TI  - Locomotion in the pulmonate snail Melampus--I. The motor pattern.
AB  - 1. The patterned neural activity that drives muscular locomotor movements in
      Melampus is generated within the central nervous system. 2. In the transition
      from quiescent state to crawling, the pattern recorded in nerves and connectives
      changes from short-duration bursts in many units to the 60-100 sec cycle of
      events recorded during tethered crawling in the semi-intact snail. 3.
      Extracellularly recorded bursts and individually recognizable spikes in pedal
      nerves are correlated with movements that occur at each stage of the cyclically
      repeated crawl-steps. 4. Intracellularly recorded pedal neurons involved in
      locomotion receive excitatory drive, inhibitory drive, or alternating excitatory
      and inhibitory drive during the step cycle.

PMID- 1976482
TI  - Locomotion in the pulmonate snail Melampus--II. Recovery after pedal ganglion
      excision.
AB  - 1. When one pedal ganglion is removed, snails first crawl using the unoperated
      side of the foot, but in 4-8 weeks the operated side exhibits an anterior-to
      posterior gradient of recovery. 2. A ganglion bud bridges the site of the missing
      ganglion and axons project from intact central ganglia into the foot. 3. Rhythmic
      activity in right and left pedal nerve pairs is correlated during locomotion in
      the regenerated snails. 4. The oscillator in the remaining pedal ganglion drives
      bilaterally coordinated activity. Regenerated projections from the cerebral
      ganglia through the bud to the remaining pedal ganglion suffice to initiate
      locomotion.

PMID- 1976483
TI  - Neuroelectrophysiology of the morphologically asymmetric habenulae of the frog.
AB  - 1. Electrophysiological recordings of the spontaneous and evoked activities of
      the frog habenular nuclei are presented. 2. The traces were recorded
      simultaneously from both habenular nuclei and an histological test was performed
      in order to show the exact location where the electrodes were inserted in the
      brain for the purpose of making the recordings. 3. The traces show a
      dissimilarity which agrees with the morphological asymmetry of these nuclei
      demonstrated histologically.

PMID- 1976484
TI  - Seasonal cyclicity in carbohydrate metabolism parameters in the European bison,
      Bison bonasus L.
AB  - 1. In 197 European bison divided into four groups (Group 1, 0-3-year-old males;
      Group 2, 0-3-year-old females; Group 3, mature bulls, over 3 years old; Group 4,
      mature cows, over 3 years old) seasonal changes in the level of lactic and
      pyruvic acids, glucose and alkaline reserve were studied. 2. Seasonal cyclicity
      was found only in lactic acid levels in all groups. 3. In the pyruvic acid level
      cyclicity was found only in males. 4. In the glucose level cyclicity was found
      only in mature cows. 5. In alkaline reserve cyclicity was found only in mature
      bison. 6. Six out of 9 acrophases of cyclic indices occurred in the period from
      the second half of August until mid-December, i.e. before the winter time.

PMID- 1976485
TI  - Prolonged neuromuscular blockade after long-term infusion of vecuronium bromide
      in the intensive care unit.

PMID- 1976486
TI  - Localization and polymorphism of a chromosome 12-specific alpha satellite DNA
      sequence.
AB  - The isolation and localization of a chromosome 12-specific alpha satellite DNA
      sequence, p alpha 12H8, is described. This clone contains a complete copy of the
      1.4-kb HindIII higher-order repeat present within the alpha satellite array on
      chromosome 12. The specificity of p alpha 12H8 was demonstrated by in situ
      hybridization and Southern blot analysis of a somatic cell hybrid mapping panel,
      both performed under high-stringency conditions. Polymorphic restriction patterns
      within the alpha satellite array, revealed by the use of the restriction enzymes
      BglII and EcoRV, were demonstrated to display Mendelian inheritance. These
      properties make p alpha 12H8 a valuable genetic marker for the centromeric region
      of chromosome 12.

PMID- 1976487
TI  - Formoterol in the treatment of nocturnal asthma.
AB  - Formoterol fumarate is a new beta 2-adrenergic agonist with a long lasting
      effect. The bronchospasmolytic effect of 12 micrograms of formoterol was compared
      with that of 200 micrograms of albuterol (salbutamol) in a single-center, double
      blind, randomized within-patient study. The drugs were given as aerosols by MDI
      to 16 patients with nocturnal asthma in a stable phase. The inhalations were
      given at 10 PM and the FEV1 values as parameter were measured before and at 1, 2,
      6, 8, 10, and 12 hours afterwards. The FEV1 6 hours after administration of
      formoterol was significantly higher than that after albuterol (ANCOVA: p =
      0.008), and this was still the case 12 hours after the test dose at 10 AM the
      following morning (ANCOVA: p = 0.009). At 4 AM, the FEV1 fell below the basic
      starting value after albuterol, whereas it remained at least 10 percent above the
      formoterol inhalation. Five patients required rescue therapy after albuterol and
      two after formoterol. We conclude that formoterol in a dose of 12 micrograms via
      MDI confers good protection against nocturnal asthma; this was only insufficient
      for some patients with severe asthma, and further studies with higher dosages in
      these patients are clearly indicated.

PMID- 1976488
TI  - Isolation of a strain of Hantaan virus from peritoneal exudate cells of a patient
      with hemorrhagic fever with renal syndrome.
AB  - A new strain of Hantaan virus (HTNV), GH716, was isolated from the peritoneal
      exudate cells (PEC) of a patient with severe hemorrhagic fever with renal
      syndrome (HFRS). The isolate was propagated in Vero E6 cells. At each passage the
      virus-infected cells were examined for HTNV with immunofluorescence technique
      using monoclonal antibodies (McAb) 25-1 and 84-1 against HTNV. From passage 5 on,
      fluorescent intensity tended to stabilize at (+++) and infectivity titer reached
      10(5) TCID50/ml. Using 14 McAb to 76-118 and BI strains of HTNV, we found that
      strain GH716 was antigenically similar to strain 76-118 (Apodemus type) and
      different from strain R22 (Rattus type), suggesting that GH716 may fall into the
      Apodemus type of HTNV. This is the first isolation of an HTNV from human PEC
      collected on the tenth day of illness. The successful isolation of strain GH716
      may provide an alternative source of obtaining HTNV during the later stages of
      HFRS.

PMID- 1976489
TI  - Advances in vascular surgery.

PMID- 1976490
TI  - Clinical studies in 500 patients with aortoarteritis.
AB  - Five hundred patients with aortoarteritis were studied in this series. The long
      term administration of small dosage of corticosteroid is effective in treating
      this disease in its active stage. The patients with renal vascular hypertension
      should be treated by percutaneous transluminal renal angioplasty or by surgery if
      indicated. About one third of the pulsations of the involved arteries were
      improved. The incidence of complications was 17% and the mortality rate was 11%
      in this series. Cerebral thrombosis was found as a common complication and
      hemorrhage as a common cause of death. Three patients died of heart failure
      without aortic regurgitation. Five-year and ten-year survival rates were 93.1%
      and 91.1% respectively.

PMID- 1976491
TI  - Neuro-endocrine type of gastric carcinoma. Immunohistochemical and electron
      microscopic studies of 100 cases.
AB  - 1,351 specimens resected surgically from 100 patients with gastric carcinoma were
      studied with PAP immunoperoxidase and ultrastructural method. The tumor cells
      were found positive for gastrin, serotonin, somatostatin and argyrophil particles
      in 19 patients. Among them the gastrin-secreting tumor cells consisted of 50% of
      the total in 4 cases, representing a separate new subtype, neuro-endocrine (NE)
      gastric carcinoma. Of the 100 cases, 16 (32%) contained NE cells among 50
      undifferentiated type, while only 3 cases (6%) contained NE cells among the
      remaining 50 cases, the well-differentiated type. These results suggest that the
      appearance of NE tumor cells is closely correlated with the degree of
      differentiation of cancer, and confirms theoretically the heterogenicity of
      gastric carcinoma, and further supports the concept that exocrine and endocrine
      type gastric cancer cells are isogenous, i.e., from the endodermal stem cells.

PMID- 1976492
TI  - [A study of the role of plasma thromboxane B2 and 6-keto-prostaglandin F1 alpha
      in epidemic hemorrhagic fever].
AB  - Plasma concentrations of Thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha
      (6-keto-PGF1 alpha) were dynamically measured with radioimmunoassay in 30
      patients of epidemic hemorrhagic fever (EHF). It was found that the levels plasma
      TXB2 significantly increased and 6-keto-PGF1 alpha decreased in EHF patients as
      compared with those in controls. The more severe the patient's condition, the
      higher the level of TXB2 and the lower the level of 6-keto-PGF1 alpha. The ratio
      of TXB2/6-keto-PGF1 alpha was parallel with the severity of the patient's
      condition. Plasma TXB and TXB2/6-keto-PGF1 alpha ratio increased significantly in
      the hemorrhagic and shock group, while 6-keto-PGF1 alpha decreased significantly
      in the shock group. The results showed that there is a distinct imbalance of TXA2
      PGI2 mediated through the increase of TXA2 and decrease of PGI2 in EHF. The
      imbalance of TXA2-PGI2 participates in the pathogenesis and pathophysiology of
      hemorrhage, shock and renal dysfunction.

PMID- 1976493
TI  - Presynaptic nicotinic receptors and the modulation of transmitter release.
AB  - Nicotine is increasingly recognized to promote transmitter release in the brain
      by a direct action on presynaptic terminals. Pharmacological evidence indicates
      that this action is mediated by nicotinic receptors. From their sensitivity to
      mecamylamine, neosurugatoxin and neuronal bungarotoxin these presynaptic
      receptors can be distinguished from alpha-bungarotoxin-sensitive muscle-type
      nicotinic receptors, and can be correlated with [3H] nicotine binding sites in
      the brain. The release of many transmitters in different brain regions is
      susceptible to stimulation by nicotine, but this effect is not ubiquitous.
      However, lesioning and subcellular fractionation studies suggest that the
      majority of brain nicotine receptors are located presynaptically, so that a
      direct influence of nicotine on transmitter release assumes considerable
      importance. Although the sensitivity of presynaptic receptors is such that they
      are likely to be partially activated by doses of nicotine obtained by smoking,
      the desensitization-induced up-regulation of nicotinic binding sites that follows
      chronic nicotine treatment raises questions about their functional status during
      tobacco usage. Chronic administration of the agonist (+)anatoxin-a also up
      regulated [3H] nicotine binding sites, and led to increased nicotine-evoked
      transmitter release in vitro. This could have implications for the involvement of
      these receptors during withdrawal.

PMID- 1976494
TI  - [Laboratory study on the relationship between drinking water and hepatoma-
      quantitative evaluation using hepatic gamma-GT method].
AB  - One to two-month-old male Fischer 344 (F-344) rats were used in this
      investigation. The experiment was devised simulating the Two-stage
      Hepatocarcinogenesis Model described by Pitot. Quantitative stereological method
      was applied to evaluate the gamma-GT enzyme altered foci (EAF) in examined liver
      slides. The results showed that pond-ditch water had an enhancement effect on the
      expression of gamma-GT in the livers of male F-344 rats, where as well water had
      no such effect. When AFB1 was given alone to the male F-344 rats after partial
      hepatectomy, there was no effect on gamma-GT, if it was followed by pond-ditch
      water the rats would express high frequency of EAF. In this experiment the effect
      of organochlorinated pesticide DDT on hepatic gamma-GT was also studied. It
      showed a strong influence on the quantity and size of EAF.

PMID- 1976495
TI  - Tolerance of rat duodenum to luminal acid.
AB  - The tolerance of the duodenal mucosa to luminal acid was investigated by
      measuring with a liquid sensor pH microelectrode technique the epithelial surface
      pH (pHs) and subepithelial tissue pH (pHt) in rat proximal (duodenal bulb,
      Brunner gland area) and distal duodenum exposed to luminal acid. Under basal
      conditions, pHs was roughly equal in both parts of the duodenum; proximal
      duodenum, 7.40 +/- 0.14 (mean +/- SEM) at the villus tip and 7.54 +/- 0.16 at the
      depth of crypt; distal duodenum, 7.46 +/- 0.19 and 7.55 +/- 0.09, respectively.
      Yet, exposure of the mucosa to luminal acid (10 mM HCl) provoked a significantly
      lesser decrease of pHs (0.25 +/- 0.13 vs 0.42 +/- 0.12 pH units) in the proximal
      duodenum, suggesting that the response of epithelial HCO3 secretion to luminal
      acid is stronger in that part of the duodenum. Further, the initial acidification
      of pHs was followed in the proximal duodenum by a secondary alkalinization of
      pHs, leading to normalization of pHs, which may suggest activation of
      compensatory protective mechanisms. pHt at the villus tip was likewise roughly
      equal in both parts of duodenum (7.29 +/- 0.05 vs 7.17 +/- 0.04), but, again,
      acidification of the luminal perfusate progressively from 10 to 100 mM HCl
      induced a much earlier and significantly more profound acidification in the
      distal than in the proximal duodenum. The possible contribution of Brunner glands
      to the greater mucosal tolerance to acid in the proximal duodenum was assessed by
      investigating whether stimulation or inhibition of Brunner gland secretion
      modulates the response of the duodenal mucosa to acid.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1976497
TI  - Retinopathy of prematurity. Proceedings of the International Workshop. Rome ,
      Italy, 30 June-1 July 1989.

PMID- 1976498
TI  - [Antagonist of NMDA receptor blocks epileptiform discharges in spinal motor
      neurons of the frog].

PMID- 1976496
TI  - Demonstration of intrathecal and systemic morphine and ST-91 effects on fed
      canine upper gut motility.
AB  - We studied the effects of opioid and adrenergic agonists and antagonists given
      systemically intravenously and intrathecally on postprandial antral and small
      bowel motility in a chronic conscious dog model. We studied eight dogs with a
      surgically implanted thoracic spinal intrathecal injection catheter, and six
      gastrointestinal manometric perfusion catheters. Morphine given intrathecally or
      intravenously induced propagated clusters of intestinal pressure activity in the
      fed dogs. The minimal effective dose for morphine was 150 micrograms/kg by the
      intrathecal route and 450 micrograms/kg by the intravenous route. ST-91 (an alpha
      2-adrenergic agonist) profoundly inhibited antral and small intestinal pressure
      activity with similar minimal effective dose (100 micrograms/kg) and duration of
      effect for both intravenous and intrathecal routes. Neither naloxone (3000
      micrograms/kg) nor combined phentolamine (1500 micrograms/kg) with propranolol
      (300 micrograms/kg) altered postprandial antral or small intestinal motility. The
      capacity of pharmacologic agents to block morphine-induced activity fronts when
      administered in the same compartment (intravenously or intrathecally) was
      investigated. The minimally effective morphine-antagonist dose for naloxone was
      similar intrathecally and intravenously (36 micrograms/kg for both routes). ST-91
      (100 micrograms/kg) when given intrathecally or intravenously blocked morphine
      induced clustered phasic pressure activity while simultaneously abolishing
      postprandial small intestine phasic pressure activity. These data suggest the
      presence of opioid and alpha 2-adrenergic receptors in the spinal cord that can
      modulate gastrointestinal motility in the postprandial state. Pharmacological
      interactions between these systems occur at spinal and target organ levels.

PMID- 1976499
TI  - [Organization of densovirus genome illustrated by the mosquito densovirus].

PMID- 1976500
TI  - [Quantitative morphofunctional changes in presynapses of the hippocampus during
      increase in the intracellular level of L-glutamate].

PMID- 1976501
TI  - [Secondary prevention after myocardial infarct].

PMID- 1976502
TI  - [Multiple sclerosis and retroviruses: new findings].

PMID- 1976503
TI  - In vivo regulation of MPF in Xenopus oocytes.
AB  - Entry into M phase in the eukaryotic cell cycle is controlled by the oscillating
      activity of MPF. The active component of MPF is now known to be the p34cdc2
      protein kinase originally found in yeast. The p34cdc2 protein kinase displays a
      characteristic M-phase-specific histone H1 kinase activity when it interacts with
      cyclins, which are proteins that oscillate through the cell cycle and are thought
      to regulate p34cdc2 activity. Cyclins can induce M phase when introduced into
      fully grown Xenopus oocytes and cyclin may play a role in normal oocyte
      maturation. Small Xenopus oocytes do not mature in response to the hormonal
      triggers which act on stage 6 oocytes. We introduced cyclin into stage 4 (small)
      Xenopus oocytes and showed that it activates MPF in these cells, probably by
      interacting with endogenous p34cdc2 kinase. We made labelled extracts from cyclin
      mRNA-injected stage 4 oocytes and used them to show differential stability of
      clam cyclins A and B at oocyte maturation. The relative stability of the two
      forms of cyclin related directly to their ability to stabilize crude MPF
      preparations from injected stage 6 oocytes.

PMID- 1976504
TI  - The Xenopus XIHbox 6 homeo protein, a marker of posterior neural induction, is
      expressed in proliferating neurons.
AB  - XIHbox 6 is an early spatially restricted marker for molecular studies of neural
      induction. The sequence of the full-length XIHbox 6 protein is reported. An
      antibody raised against a beta-galactosidase/XIHbox 6 fusion protein was used to
      analyze the expression of XIHbox 6 proteins during frog embryogenesis. The
      anterior border of XIHbox 6 expression lies just posterior of the
      hindbrain/spinal cord junction. Immunostaining extends the entire length of the
      spinal cord. A much weaker transient expression with a similar anterior border is
      observed in mesoderm. Almost all nuclei in the newly closed spinal cord contain
      XIHbox 6. The number of positive nuclei decreases over the next stages of
      development, until in later embryos XIHbox 6 is restricted to nuclei of the
      dividing neuroepithelium, and not the mantle or marginal zones of the spinal
      cord. When the limb buds begin to grow, there is a second burst of XIHbox 6
      expression in proliferating neurons of the cervical and lumbar enlargements,
      where nerves arise that supply the limbs. The data suggest that XIHbox 6
      expression is spatially and temporally restricted to immature neurons of the
      spinal cord, before their differentiation into mature neurons.

PMID- 1976505
TI  - [Biological hypotheses in obsessive-compulsive disorder].
AB  - Biological hypothesis in obsessive-compulsive disorder is recent and firstly
      initiated through pharmacological data. The supporting evidences are scant but
      sufficiently provocating; the review of the literature data on these hypothesis
      suggests more questions than concluding responses; the introduction of new
      psychobiological models (like ethologic, cybernetic, cognitive and behavioral
      models...) and the functional "cutting" (or the transnosologic approach) of the
      disorder may allow more specific applications for the neurobiological research,
      and more refined predictions on clinical and experimental observations (responses
      to psychoactive drugs, biological abnormalities...).

PMID- 1976506
TI  - Equine insect hypersensitivity: skin test and biopsy results correlated with
      clinical data.
AB  - Forty-four seasonally pruritic horses and 21 asymptomatic horses in Florida, USA,
      were tested for insect, grass and mould hypersensitivity by intradermal injection
      of allergenic extracts. The affected horses ranged in age from 10 months to over
      30 years and included a variety of breeds. Affected horses reacted to varying
      dilutions of extracts made from Culicoides, mosquitoes, horse flies and black
      flies. Reactions to Culicoides were more intense than those caused by injection
      of antigens from other arthropods. Mild pruritus existed from the end of February
      until the end of June when the condition worsened and remained severe until
      November when it improved to an asymptomatic state. Histopathological examination
      of skin biopsies demonstrated changes compatible with arthropod hypersensitivity.
      Three clinical syndromes associated with insect hypersensitivity were described
      as follows: 1) horses with lesions on face, ears, mane, withers, rump and tail;
      2) horses with lesions on face, ears, intermandibular space, chest, belly and
      groin, and 3) those with a combination of dorsal and ventral lesions.

PMID- 1976507
TI  - Protein--DNA contacts in the structure of a homeodomain--DNA complex determined
      by nuclear magnetic resonance spectroscopy in solution.
AB  - The 1:1 complex of the mutant Antp(C39----S) homeodomain with a 14 bp DNA
      fragment corresponding to the BS2 binding site was studied by nuclear magnetic
      resonance (NMR) spectroscopy in aqueous solution. The complex has a molecular
      weight of 17,800 and its lifetime is long compared with the NMR chemical shift
      time scale. Investigations of the three-dimensional structure were based on the
      use of the fully 15N-labelled protein, two-dimensional homonuclear proton NOESY
      with 15N(omega 2) half-filter, and heteronuclear three-dimensional NMR
      experiments. Based on nearly complete sequence-specific resonance assignments,
      both the protein and the DNA were found to have similar conformations in the free
      form and in the complex. A sufficient number of intermolecular 1H-1H Overhauser
      effects (NOE) could be identified to enable a unique docking of the protein on
      the DNA, which was achieved with the use of an ellipsoid algorithm. In the
      complex there are intermolecular NOEs between the elongated second helix in the
      helix-turn-helix motif of the homeodomain and the major groove of the DNA.
      Additional NOE contacts with the DNA involve the polypeptide loop immediately
      preceding the helix-turn-helix segment, and Arg5. This latter contact is of
      special interest, both because Arg5 reaches into the minor groove and because in
      the free Antp(C39----S) homeodomain no defined spatial structure could be found
      for the apparently flexible N-terminal segment comprising residues 0-6.

PMID- 1976508
TI  - Expression of a homeobox gene in the chick wing bud following application of
      retinoic acid and grafts of polarizing region tissue.
AB  - Homeobox gene XlHbox 1 is expressed in a mesodermal gradient in vertebrate
      forelimbs with maximal expression anteriorly and proximally and may encode
      positional values. In chick wing buds, anterior cells can be reprogrammed to form
      posterior structures by grafts of polarizing region tissue and by beads soaked in
      retinoic acid (RA), which is a good candidate for an endogenous morphogen.
      Applications of RA anteriorly or at the bud apex, treatments which produce
      duplicated digits or truncations respectively, substantially increase the extent
      of mesodermal XlHbox 1 expression. Polarizing region grafts that also produce
      additional digits lead to a moderate increase. The effects of RA application and
      the behaviour of transplanted tissue show that only anterior cells are competent
      to express XlHbox 1 and that expression is cell autonomous. Ectodermal expression
      in wing buds is enhanced by RA but not by polarizing region grafts and
      ectoderm/mesoderm recombinations show that the mesoderm is irreversibly affected.
      The changes in mesodermal expression do not fit the predictions of the simple
      model that XlHbox 1 encodes anterior positional values but are correlated with a
      series of novel malformations of the shoulder girdle which, in normal wing buds,
      is derived from cells expressing XlHbox 1.

PMID- 1976509
TI  - Mouse B lymphocyte specific endocytosis and recycling of MHC class II molecules.
AB  - In B lymphocytes, the processing of exogenous proteins and the subsequent binding
      of antigenic peptides to class II molecules encoded by the major
      histocompatibility complex (MHC) occurs most likely within endocytic
      compartments. To examine the endocytic transport of MHC class II molecules, we
      used (i) surface iodination followed by internalization, pronase treatment and
      immunoprecipitation, (ii) in situ iodination of endosomal compartments, and (iii)
      confocal microscopy to visualize the fate of fluorescence coupled Fab fragments.
      In murine I-Ak, I-Ek positive B lymphoma cells, cell surface MHC class II
      molecules are partially protected from pronase digestion after 15 min at 37
      degrees C and recycled back to the cell surface within the next 30 min. The
      fluorescence coupled Fab fragments are delivered to juxtanuclear endocytic
      compartments in 15 min. In contrast to the murine B cells, L fibroblasts
      transfected with either I-A alpha beta k or I-E alpha k beta k,d fail to
      internalize their surface class II molecules. A fraction of class II molecules,
      however, is still present in endosomal compartments as detected after in situ
      iodination in L fibroblasts. We conclude that the recipient L fibroblasts lack
      one or several factors needed for the transport of MHC class II molecules from
      the cell surface to the endosomes. We suggest that in murine B lymphoma cells,
      antigenic peptides can gain access to a pool of recycling class II molecules
      whereas in L cells they meet newly synthesized class II molecules targeted to the
      endosomal compartments.

PMID- 1976510
TI  - Different forms of Ultrabithorax proteins generated by alternative splicing are
      functionally equivalent.
AB  - The Ubx gene of Drosophila normally produces several forms of Ubx proteins
      through alternative splicing of two microexons. We describe here two new viable
      Ubx mutations that show similar and almost wild-type adult phenotypes. Molecular
      characterization has shown that one of them, UbxMX17, is an inversion within the
      Ubx transcription unit including one of the microexons involved in alternative
      splicing. This results in mutant flies possessing a very abnormal array of Ubx
      proteins, probably including spliced forms not present in wild-type flies. Yet
      these protein products successfully substitute for the normal ones and allow
      virtually normal Ubx function. We argue that the different Ubx proteins are
      developmentally equivalent and that the slight mutant phenotype observed in
      UbxMX17 flies is not due to the abnormal set of Ubx proteins but to a breakpoint
      in a cis-regulatory region.

PMID- 1976511
TI  - Thyroid nuclear factor 1 (TTF-1) contains a homeodomain and displays a novel DNA
      binding specificity.
AB  - The cDNA for TTF-1, a thyroid nuclear factor that binds to the promoter of
      thyroid specific genes, has been cloned. The protein encoded by the cDNA shows
      binding properties indistinguishable from those of TTF-1 present in nuclear
      extracts of differentiated rat thyroid cells. The DNA binding domain of TTF-1 is
      a novel mammalian homeodomain that shows considerable sequence homology to the
      Drosophila NK-2 homeodomain. TTF-1 mRNA and corresponding binding activity are
      detected in thyroid and lung. The chromosomal localization of the TTF-1 gene has
      been determined in humans and mice and corresponds to chromosomes 14 and 12,
      respectively, demonstrating that the TTF-1 gene is not located within previously
      described clusters of homeobox-containing genes.

PMID- 1976512
TI  - Thymic selection defines multiple T cell receptor V beta 'repertoire phenotypes'
      at the CD4/CD8 subset level.
AB  - We describe here the use of a sensitive and accurate multiprobe V beta RNase
      protection assay in characterizing the expression levels of 17 V beta genes in
      separated CD4+ and CD8+ subsets of selected mouse strains. The IE-reactive V beta
      genes (V beta s 11, 12, 5.1 and 16) showed various patterns of skewed subset
      expression in different strains, suggesting additional influences of IA, class I,
      and non-MHC genes in the selection process. Clonal deletion of V beta 11- and V
      beta 12-bearing T cells, among others, was skewed strongly towards the CD4+
      subset in many IE+ mouse strains, supporting the notion that negative selection
      can cause incomplete, subset biased, V beta clonal deletions. Broad analysis in
      separated CD4+ and CD8+ subsets gave improved resolution of V beta repertoire
      selection, and revealed significant strain and/or subset specific skewing for
      additional V beta genes; with consistent bias towards higher expression of V beta
      7 and V beta 13 in the CD8+ subset, and V beta 15 in the CD4+ subset of most
      mouse strains. The influence of diverse non-MHC ligands in V beta repertoire
      selection was further illustrated by the identification of unique V beta
      repertoires for six different MHC-identical (H2k) strains. Such polymorphisms in
      TCR repertoire expression may help to define better disease susceptibility
      phenotypes.

PMID- 1976513
TI  - Transcriptional and post-transcriptional regulation of tyrosine hydroxylase gene
      by protein kinase C.
AB  - The role played by protein kinase C (PKC) in TH gene regulation was investigated
      at transcriptional and post-transcriptional levels using PC12 cells. The cells
      were treated with the phorbol ester TPA, which not only activates PKC but also
      causes down-regulation. PKC levels were monitored by [3H]PDBU binding assay and
      by using an anti-PKC antibody that detected intact PKC (79 kd) as well as its
      catalytic and regulatory domains. The [3H]PDBU binding to the membrane-associated
      PKC increased within 15-30 min of TPA treatment; thereafter total cellular
      [3H]PDBU binding decreased to a minimum of 20% of the control at 8 h. The rate of
      decrease in binding was greater than the decrease in the intensity of the
      staining of PKC holo enzyme visualized by anti-PKC antibody. TH mRNA levels,
      measured over the same time period, rose within 15 min of TPA treatment to peak
      at 4 h and subsequently declined below control level, paralleling the depletion
      of PKC. If cells depleted of PKC were reincubated in the normal medium, a
      recovery in PKC level was seen and, in parallel, TH mRNA levels increased to
      above control level. Furthermore, if down-regulation of PKC was prevented by
      incubating the cells with the protease inhibitor leupeptin, a decrease beyond
      control level in TH mRNA was not observed. TPA rapidly induced TH gene
      transcription; a maximal increase of two-fold was observed at 15 min, but the
      transcriptional rate then declined although it did not decrease beyond control
      values after 8 and 24 h of TPA treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1976515
TI  - Mechanism of action of urocanase. Specific 13C-labelling of the prosthetic NAD+
      and revision of the structure of its adduct with imidazolylpropionate.
AB  - 1. [4-13C]Nicotinate was synthesised and used to support the growth of a
      nicotinate auxotrophic mutant of Pseudomonas putida. 13C-NMR spectroscopy of the
      isolated urocanase confirmed the efficient incorporation of 13C into C4 of the
      nicotinamide ring of the tightly bound NAD+ cofactor. 2. beta-[( 2'-13C]Imidazol
      4-yl)propionate was synthesised according to known procedures and used for
      inhibition of the 13C-labelled urocanase. An increase in the absorbance at 330 nm
      indicated adduct formation between enzyme-bound NAD+ and inhibitor. The adduct
      was stabilised by oxidation with phenazine methosulfate and isolated using a
      slight modification of the procedure of Matherly et al. [Matherly, L. H.,
      DeBrosse, C. W. & Phillips, A. T. (1982) Biochemistry 21, 2789-2794]. 3. The 13C
      NMR spectrum of the doubly labelled adduct, [4-13C]NAD-[2'
      13C]imidazolylpropionate, showed no one-bond 13C-13C coupling between labelled
      sites. The 1H-NMR spectrum of this adduct in 2H2O showed only one imidazole
      signal, which appeared as a doublet (1JC-H = 212 Hz), confirming the presence of
      a proton at the labelled C2'. The lack of a C5' signal and further NMR data
      provide evidence for a C-C bond between C4 of the nicotinamide and C5' of the
      imidazole ring. 4. The revised structure for the enzymatically formed addition
      complex suggests a novel mechanism for the urocanase reaction which is not only
      chemically plausible but also explains the previously observed urocanase
      catalysed exchange of the C5 proton of urocanate and of beta-(imidazol-4
      yl)propionate.

PMID- 1976514
TI  - Oct-6: a POU transcription factor expressed in embryonal stem cells and in the
      developing brain.
AB  - A family of octamer binding proteins is expressed during mouse development. Oct-4
      and Oct-6 have been identified as two octamer binding proteins present in
      embryonal stem cells. Here we report the complementary DNA cloning and
      characterization of the mouse Oct-6 gene. The protein of 448 amino acids contains
      a glycine/alanine-rich amino terminal region, a histidine-rich sequence with
      homology to a region of kininogen associated with clotting, a POU domain and a
      short proline/histidine-rich carboxy terminal region. Expression of Oct-6 in HeLa
      cells is sufficient for transcriptional activation from the octamer motif,
      identifying Oct-6 as a transcription factor. The Oct-6 expression is
      downregulated upon embryonic stem cell differentiation increasing again during
      brain development. Expression in brain is present in certain areas of
      telencephalon, mesencephalon and brain stem with abundant expression in the
      cortex anlagen and in the developing colliculi. Thus Oct-6 is a new octamer
      binding transcription factor specifically regulated during mouse development.

PMID- 1976516
TI  - Activation of soluble guanylate cyclase by carbon monoxide and inhibition by
      superoxide anion.
AB  - Human platelet soluble guanylate cyclase activity was studied with respect to the
      function of its heme-containing regulatory subunit. As an enzyme source, the
      10,000 x g supernatant was used and, since its specific activity proved to be too
      low for inhibition studies, also a partially purified preparation was employed.
      The partially purified enzyme was stimulated about 2.5-fold by carbon monoxide
      and this effect was abolished by illumination with visible light. Sodium
      nitroprusside also increased the basal activity about fourfold, which, however,
      is much less than the greater than 100-fold stimulation seen with the
      supernatant. Superoxide anions generated by the xanthine/xanthine-oxidase system
      were strongly inhibitory in the enriched preparation as well as in the CO
      stimulated platelet supernatant (median effector concentration = 0.1 mU/ml).
      Unlike CO and NO, the effect of superoxide cannot be mediated through the heme
      containing regulatory subunit, since heme-free enzyme, which could not be
      activated by NO or CO, was inhibited to the same extent as the heme-containing
      enzyme. Superoxide dismutase did not influence the basal activity, but resulted
      in a synergistic stimulation in the presence of CO. When Mn2+ replaced Mg2+ as a
      cofactor, the basal activity was higher but superoxide could not inhibit the
      enzyme, possibly due to the superoxide-dismutase-like activity of Mn2+.
      Superoxide turned out to be a potent and reversible inhibitor of soluble
      guanylate cyclase which, together with endothelium-derived relaxing factor,
      recently identified as NO, could form a physiologically relevant regulatory
      effector system.

PMID- 1976517
TI  - EEC concerted action on cellular degeneration and regeneration studied with PET.
      Modelling expert meeting blood flow measurement with PET--Orsay, 12-13 October
      1989.

PMID- 1976518
TI  - Effect of two consecutive administrations of GHRH in children with constitutional
      growth delay.
AB  - It has been suggested that children with constitutional growth delay might have a
      transient immaturity of the neurotransmitter pathways necessary for the control
      of growth hormone releasing hormone (GHRH) secretion. In this study we evaluated
      the effects of two consecutive GHRH boluses (1 microgram/kg, i.v.) in nine
      prepubertal boys with constitutional growth delay. Growth hormone (GH) responses
      to GHRH administration were similar to that observed in normal children (first
      GHRH bolus, GH net incremental area under the curve (nAUC) +/- SE: 788 +/- 244 vs
      984 +/- 242 ng/ml per hour; second bolus, GHnAUC: 657 +/- 122 vs 541 +/- 129
      ng/ml per hour, respectively). These data suggest that no relevant abnormalities
      in the mechanisms determining the somatotroph sensitivity to GHRH are present in
      children with constitutional growth delay.

PMID- 1976519
TI  - Transient electrocardiographic changes suggesting myocardial ischaemia in newborn
      infants following tocolysis with beta-sympathomimetics.
AB  - Serial electrocardiograms (ECGs) were studied prospectively in 80 apparently
      healthy newborn infants; 30 infants exposed in utero to prolonged tocolytic
      therapy (21 to ritodrine and 9 to isoxsuprine) and 50 infants non-exposed in
      utero to drugs (control group) matched for gestational age, Apgar score, and
      birth weight. Duration of exposure to tocolysis was at least 30 days (30-180
      days) with an oral dosage of 10 mg 3 times daily. ECGs were graded for changes
      suggestive of ischaemia using the arbitrary grading system described by Jedeikin
      et al. In all infants with ECG features of myocardial ischaemia, serum creatine
      phosphokinase iso-enzyme (CK-MB) activity was measured. Six out of 21 infants to
      ritodrine and six out of nine infants exposed to isoxsuprine showed a degree of
      ECG ischaemia which persisted for several weeks. No control infant presented
      grade 2 or 3 ECG changes after the 5th day of life. The results of this study
      seem to show that prolonged tocolytic therapy with beta-sympathomimetics has side
      effects on the fetal myocardium and suggest that this treatment be reserved only
      for selective cases and/or for short periods of time.

PMID- 1976520
TI  - Cytokine-induced generation of multinucleated giant cells in vitro requires
      interferon-gamma and expression of LFA-1.
AB  - Multinucleated giant cells (MGC), which are a common feature of various
      pathologic states, were generated in vitro by cytokine-stimulation of human
      peripheral blood monocytes. As expected, conditioned medium, i.e. the supernatant
      of concanavalin A-stimulated peripheral blood mononuclear cells, readily caused
      generation of MGC. Addition of a monoclonal antibody (mAb) against interferon
      gamma (IFN-gamma) completely abrogated this effect. IFN-gamma alone, however, had
      a much smaller effect than the conditioned medium. All other cytokines tested
      [including interleukin (IL)2, IL4 and tumor necrosis factor-alpha, which are
      known to activate monocytes] did not induce MGC nor did they enhance the effect
      of IFN-gamma. Formation of MGC could almost entirely be inhibited by mAb to the
      alpha or beta chain of LFA-1 and to a lesser extent by relatively high
      concentrations of a mAb against ICAM-1, one of the ligands of LFA-1. In contrast
      to the anti-IFN-gamma mAb that had no significant effect on the formation of
      monocyte clusters, mAb against LFA-1 inhibited clustering very efficiently.
      Antibodies directed to a number of different antigens present on the surface of
      monocytes (alpha chains of CR3 and CR4, HLA class I and II molecules, CD14 and
      CD16 antigens) had little or no effect on the generation of MGC. IFN-gamma, but
      not the concanavalin A-induced supernatant clearly enhanced expression of LFA-1
      and ICAM-1 on monocytes. The results indicate that cytokine-induced generation of
      MGC is not possible without IFN-gamma, but most probably additional factor(s)
      enhance this effect. The mechanism(s) by which IFN-gamma promotes monocyte fusion
      apparently includes, among others, up-regulation of LFA-1 whose expression seems
      to be necessary but not sufficient for fusion.

PMID- 1976522
TI  - The V kappa gene repertoire in the human germ line.
AB  - The question of how many V kappa gene segments exist in the human germ line was
      addressed. Seventy-five V kappa genes of the kappa locus and twenty-five V kappa
      genes localized outside of the locus ("orphons") had been cloned previously; 67
      of the genes and 19 of the orphons had already been sequenced yielding 36 and 1
      potentially functional V kappa genes, respectively, the remaining ones being
      pseudogenes. We now (a) determined the relative hybridization intensities of the
      cloned V kappa genes and orphons, (b) identified the bands in blot hybridizations
      of genomic DNA digests with the cloned genes and orphons, (c) determined the band
      intensities in the genomic DNA digests from two individuals and one cell line,
      (d) normalized the results with the help of the C kappa gene segment which is
      present in the haploid genome in one copy, (e) compared the genomic blot
      hybridization patterns with patterns of equimolar mixtures of the cloned V kappa
      genes and orphons, and (f) defined the bands and fractional intensities in bands
      that could not be assigned to cloned genes or orphons. From the resulting data we
      conclude that there are 5-7 still uncloned V kappa genes in germ-line DNA in
      addition to the 75 known V kappa genes and in addition to the 25 orphons 12-15
      orphon candidates. It appears that the rheumatoid factor light chains of the Wa
      and 6B6.6 idiotypes are coded for by one V kappa III gene each. It is concluded
      that the kappa locus comprises no more than 50 potentially functional genes and
      no more than 85 V kappa genes altogether.

PMID- 1976521
TI  - Differential expression of interleukin 1 alpha by Thy-1+ and Thy-1- lung
      fibroblast subpopulations: enhancement of interleukin 1 alpha production by tumor
      necrosis factor-alpha.
AB  - The purpose of this investigation was to determine whether subpopulations of
      murine lung fibroblasts produced interleukin 1 (IL 1). We previously identified
      two major populations of pulmonary fibroblasts based on the presence or absence
      of Thy-1. Thy-1+ and Thy-1- subsets synthesize fibronectin and type I and III
      collagen, but only the Thy-1- population displays class II major
      histocompatibility complex antigens after stimulation with interferon-gamma and
      presents antigen to T helper clones. Interestingly, in the current study we
      determined that only Thy-1- fibroblast lines and clones synthesized IL 1.
      Although constitutive production was low, tumor necrosis factor -alpha (TNF
      alpha) stimulated 5-20-fold increases in IL 1 production in Thy-1- fibroblasts.
      The Thy-1+ fibroblasts did not produce IL 1 even after TNF-alpha treatment.
      Northern blot analysis of TNF-alpha treated cells revealed that in the Thy-1-
      subset increased mRNA levels for IL 1 alpha were detected, while IL 1 beta mRNA
      was not detected. Furthermore, IL 1 activity from TNF-alpha-treated Thy-1-
      fibroblast membranes and supernatants was completely neutralized by IL 1 alpha
      specific antibodies. These observations support the hypothesis that the antigen
      presenting Thy-1- subset is important for promoting the inflammation associated
      with pulmonary fibrosis. In addition, the existence of functional subsets of lung
      fibroblasts is further substantiated by differential expression of IL 1.

PMID- 1976523
TI  - Resistance to murine cutaneous leishmaniasis is mediated by TH1 cells, but
      disease-promoting CD4+ cells are different from TH2 cells.
AB  - A limiting dilution system has been used for quantitative analysis of antigen
      reactive T cells producing interleukin (IL)2, IL4 and interferon (IFN)-gamma in
      the course of murine infection with Leishmania major. The precursor frequencies
      of CD4+ cells with the potential for production of IFN-gamma, which has been
      associated with TH1 cells, are much higher in resistant than in susceptible mice,
      whereas the reverse is found for CD4+ cells secreting IL4 which have been
      classified as TH2 cells. Our results allow a better understanding of the relative
      contribution of these cell types at various stages of disease and can be
      summarized as follows: (a) secretion of IL4 can be demonstrated in short-term
      clonal cultures of CD4+ cells from L. major-infected mice, (b) CD4+ cells
      releasing IL2, suggested to be a characteristic of TH1 cells that predominate in
      resistant mice, can also be detected in susceptible mice at any time of
      infection, (c) both IL2 and IL4 are released by the progeny of individual T cells
      from susceptible mice and (d) the kinetics of precursor frequencies in
      genetically susceptible mice protected against the disease by prophylactic
      treatment are different from those of congenitally resistant mice, thus
      indicating that the development of lymphokine-producing T cells and the
      establishment of protective immunity may be regulated differently in those mice.
      The data suggest that resistance to disease is correlated with the presence of
      IFN-gamma-producing TH1 cells, while susceptibility is associated with CD4+ cells
      that do not segregate into the TH1 or TH2 subset but display an overlapping
      pattern of lymphokine activities.

PMID- 1976524
TI  - Does enhanced sympathetic tone contribute to angiotensin II hypertension in rats?
AB  - To determine whether enhanced sympathetic tone contributes to the maintenance of
      chronic angiotensin II (A II, 10 ng/min i.v. for 10 days) hypertension in rats,
      sympathetic activity was assessed in hypertensive and control rats by measuring
      norepinephrine (NE) turnover (alpha-methyl-p-tyrosine) in peripheral organs and
      by measuring depressor responses to ganglionic blockade in conscious rats.
      Pressor responses to methoxamine (1-8 micrograms/min) and arginine vasopressin
      (0.5-4 ng/min) were also obtained in rats with ganglionic blockade. Chronic A II
      infusion produced significant hypertension (mean +/- S.E. tail cuff pressure: 176
      +/- 5 vs. 134 +/- 2 mm Hg in controls; n = 23 each group) but there were no
      significant differences in NE turnover in heart, kidney, skeletal muscle, or
      intestine in hypertensive rats compared with controls. Ganglionic blockade
      produced a significantly larger decrease in mean arterial pressure in A II
      treated rats when compared with controls (73 +/- 7 vs. 38 +/- 2 mm Hg, n = 18 for
      each group). Dose-response curves for methoxamine and vasopressin were not
      significantly different between groups. The results suggest that the maintenance
      of chronic A II hypertension does not involve postsynaptic interactions between A
      II and the sympathetic system. The NE turnover data do not support the hypothesis
      that rats with chronic A II hypertension have enhanced sympathetic tone.

PMID- 1976525
TI  - Identification of kainic and quisqualic acid receptors on inner retinal cells of
      the salamander Ambystoma mexicanum.
AB  - The presence of kainic (KA) and quisqualic acid (QA) receptors on inner retinal
      neurones of the axolotl Ambystoma mexicanum has been studied using intracellular
      recording techniques. In the presence of CoCl2, which blocks neurotransmitter
      release, KA and QA depolarized the membrane. The minimum concentration of KA that
      induced a response was 1 microM and a maximum response was obtained with 10
      microM (EC50: 3 microM). The operating range of QA was between 0.5 and 5 microM
      with an EC50 of 1 microM. These data show that inner retinal cells of the axolotl
      are sensitive to KA and QA. Cis-2,3-piperidine dicarboxylic acid (PDA, 3 mM)
      completely blocked responses to 5 microM KA, but not those induced by 2 microM
      QA. This suggests that the KA- and QA-sensitive receptors on inner retinal cells
      of the salamander are pharmacologically different and that PDA can be a valuable
      tool in distinguishing KA- and QA-sensitive receptors on these neurones.

PMID- 1976526
TI  - Involvement of vasopressin in the cardiovascular effects of quinpirole.
AB  - The effects of quinpirole, a specific dopamine D2 receptor agonist, were
      investigated on cardiovascular responses and plasma levels of catecholamines and
      vasopressin in two groups of conscious dogs: (1) control dogs and (2) dogs with
      diabetes insipidus (i.e. animals surgically deprived of vasopressin). In normal
      dogs, i.v. quinpirole (30 micrograms/kg) elicited a decrease in blood pressure
      associated with a rise in both plasma catecholamine and vasopressin levels. In
      dogs with diabetes insipidus, i.v. quinpirole induced a more marked decrease in
      blood pressure than in normal dogs. Quinpirole did not change plasma
      noradrenaline and vasopressin levels in dogs with diabetes insipidus. The present
      study demonstrates that the decrease in blood pressure elicited by quinpirole is
      associated with an increase in vasopressin release, which counteracts the
      hypotensive effect of the the dopamine D2 receptor agonist.

PMID- 1976528
TI  - Polyamines non-competitively inhibit [3H]3-PPP binding to sigma receptors.

PMID- 1976527
TI  - Effect of fenoldopam in dogs with spontaneous renal insufficiency.
AB  - Fenoldopam administration orally or i.v. resulted in significant increases in
      paraaminohippuric acid (PAH) clearance in both four control dogs and four dogs
      with chronic renal failure. Oral fenoldopam resulted in significant plasma levels
      of fenoldopam sulfate metabolites. One metabolite, fenoldopam-8-sulfate, a
      potential inhibitor of organic anion transport, did not depress renal cortical
      slice accumulation of PAH. The data therefore indicate that in dogs with chronic
      renal failure, PAH clearance after fenoldopam administration is a reliable
      measure of renal plasma flow, and fenoldopam can result in an increase in renal
      plasma flow.

PMID- 1976529
TI  - (2S,3S,4S) alpha-(carboxycyclopropyl)glycine is a novel agonist of metabotropic
      glutamate receptors.

PMID- 1976531
TI  - Effects of beta-adrenoceptor antagonists on cardiac function in ischemic
      reperfused myocardium of the isolated working rabbit heart.
AB  - The effects of beta-adrenoceptor antagonists (dl-nebivolol, atenolol and
      propranolol) and of 1-nebivolol on cardiodynamics and mitochondrial oxidative
      phosphorylation were studied in the isolated working rabbit heart subjected to
      normothermic global ischemia, followed, in some cases, by reperfusion. The hearts
      were pretreated with the different drugs (0.32 mg/l) 30 min before the start of
      ischemia, dl-Nebivolol and propranolol provided protection for both cardiodynamic
      and mitochondrial functions, as did l-nebivolol, which lacks beta-adrenoceptor
      blocking properties, while atenolol failed to protect mechanical activity and
      cardiac mitochondria against the effects of ischemia and post-ischemic
      reperfusion. Catecholamine depletion with reserpine did not have a beneficial
      effect on the recovery of cardiodynamic and mitochondrial function during post
      ischemic reperfusion. It is concluded that the beneficial effects of beta
      blockers on the ischemic and reperfused myocardium can not be explained by a
      specific beta-blocking action alone.

PMID- 1976530
TI  - Pharmacological evaluation of the beta-adrenoceptor agonist and thromboxane
      receptor blocking properties of 1-benzyl substituted trimetoquinol analogues.
AB  - The beta 1- and beta 2-adrenoceptor agonist and thromboxane A2 (TXA2) antagonist
      properties of trimetoquinol (TMQ, I) and 1-benzyl substituted TMQ analogues [3'
      iodo-4',5'-dimethoxy TMQ, II; 3',5'-diiodo-4'-dimethoxy TMQ, III; 3',4'-dimethoxy
      5'-nitro TMQ, IV; 3',4'-dimethoxy-5'-amino TMQ; V; and 3',4'-dimethoxy TMQ, VI]
      were studied in guinea pig atria (beta 1) and trachea (beta 2), and in rat
      thoracic aorta and human platelets, respectively. The rank order of agonist
      activities in beta 1- and beta 2-adrenoceptor tissues was IV greater than or
      equal to I greater than II greater than V greater than III greater than VI and I
      greater than II = IV = V greater than VI greater than III, respectively. An
      increase of beta 2/beta 1-selectivity (2- to 3-fold) was observed for analogues V
      and VI as compared to TMQ. The rank order of inhibitory potency against U46619
      induced contraction of rat aorta and human platelet aggregation and secretion was
      the same (I = II = III greater than IV greater than V greater than VI). The
      results show that varying the substituents at the 3'- and 5'-positions of the
      trimethoxybenzyl group of TMQ produces compounds which give different profiles of
      biological activity for beta-adrenoceptor agonism versus TXA2 antagonism. Certain
      TMQ analogues, notably analogue V, showed a greater selectivity as beta 2
      receptor agonists and TXA2 antagonists in vascular smooth muscle than the parent
      drug (TMQ), and the iodinated analogues (II and III) have promise as potential
      radioligands or photoaffinity probes for thromboxane A2 receptors.

PMID- 1976532
TI  - Efferent connections of the A1 noradrenergic cell group: a DBH
      immunohistochemical and PHA-L anterograde tracing study.
AB  - Immunohistochemical localization of the catecholamine biosynthetic enzymes
      tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH), and
      phenylethanolamine N-methyltransferase (PNMT) was employed to reveal the
      anatomical organization of the A1 noradrenergic cell group in the caudal
      ventrolateral medulla oblongata of the rat. Subsequently, the supraspinal
      efferent axonal projections of A1 were investigated with a view to elucidating
      the anatomical substrates underlying its postulated function in central fluid and
      cardiovascular homeostasis. Within the caudal medulla, DBH-positive/PNMT-negative
      (noradrenergic) neurons were observed extending bilaterally through the
      ventrolateral medullary reticular formation from upper cervical spinal cord
      levels to the level of the area postrema. At the rostral pole of A1, its neurons
      intermingled with PNMT-immunoreactive perikarya of the more rostrally situated C1
      adrenergic cell group. Discrete injections of the anterogradely transported plant
      lectin Phaseolus vulgaris leucoagglutinin (PHA-L) into A1 resulted in terminal
      labeling in a number of presumptive efferent target sites including the nucleus
      of the solitary tract, rostral ventrolateral medulla, dorsal parabrachial
      nucleus, Kolliker-Fuse nucleus, central grey, dorsomedial nucleus of the
      hypothalamus, perifornical region, zona incerta, lateral hypothalamus,
      paraventricular nucleus of the hypothalamus, supraoptic nucleus, bed nucleus of
      the stria terminalis, and organum vasculosum of the lamina terminalis. Tissue
      sections adjacent to those reacted for PHA-L were processed immunohistochemically
      for DBH to determine if anterogradely labeled terminals were localized in regions
      that demonstrated appropriate immunoreactivity. The majority of regions in which
      PHA-L terminal labeling was present also exhibited moderate to intense DBH
      activity. These experiments provide neuroanatomical evidence for direct efferent
      pathways from the A1 noradrenergic cell group to a number of supraspinal sites
      that have been reliably implicated in the neural circuitry underlying the central
      regulation of fluid and cardiovascular homeostasis. Furthermore, the results
      suggest a selective anatomical interrelation between A1 and sites in the basal
      forebrain and hypothalamus in which vasopressinergic neurons have been previously
      demonstrated. It is postulated that the noradrenergic A1 projections observed in
      this investigation represent the morphological substrate through which A1 exerts
      a significant influence on cardiovascular regulatory mechanisms.

PMID- 1976534
TI  - [Job organization, ethics and deontology in the work of the medical personnel at
      a feldsher-midwife center].

PMID- 1976535
TI  - [An analysis of the expenditure of work time by paramedical personnel in feldsher
      midwife centers].

PMID- 1976533
TI  - Neuronal growth cone migration.
AB  - The neuronal growth cone is a semi-autonomous portion of the developing neuron
      that is highly specialized for motile activity. Migrating neurons may share some
      features with neuronal growth cones. I review some of what has been learned about
      growth cone initiation, the differentiation of axons and dendrites, the role of
      the cytoskeleton in motility, the movements of membrane vesicles, the factors
      regulating the rate and direction of growth cone movement, and the further
      differentiation of growth cones as they enter the target area and initiate
      synaptogenesis. Where appropriate, I draw comparisons to what is known about the
      migration of neurons.

PMID- 1976536
TI  - [The feldsher as dispatcher at the display screen].

PMID- 1976537
TI  - Effect of sulfasalazine on spermatogenesis.

PMID- 1976538
TI  - Seasonal incidence of water mites (Arrenurus sp.) parasitising mosquito vectors
      at Tezpur, Assam, India.

PMID- 1976539
TI  - [Accurately fitting plasma welding with contraction eliminator].

PMID- 1976540
TI  - Benzodiazepines as antianxiety agents.

PMID- 1976541
TI  - Determinants of low birthweight among the Mendi of Sierra Leone: implications for
      medical and socio-economic strategies.
AB  - In order to identify the most appropriate interventions to reduce the amount of
      low birthweight among the Mendi people of Sierra Leone, the seasonal pattern of
      birthweights has been studied in three hospitals and compared with the incidence
      of known risk factors. Malaria and pregnancy-induced hypertension are shown to
      contribute to the excess low birthweight during the rainy season, particularly in
      primiparous women. There are no significant seasonal food shortages in this
      population and the best correlate for the bimodal seasonal excesses of low
      birthweight is the amount of agricultural work performed by the women during
      planting and harvesting. The significance of this for the choice of strategies to
      increase agricultural productivity is discussed.

PMID- 1976542
TI  - Blood pressure profiles and perinatal outcome in pregnant black women in Pelonomi
      Hospital, Bloemfontein, South Africa.
AB  - In a retrospective study, the antenatal records of 241 consecutive patients were
      analyzed. Maternal gravidity, age, blood pressure recordings, and fetal
      gestational age at birth, weight and perinatal deaths were recorded. Blood
      pressure recordings were done by the clinic staff with the patient in the supine
      position tilted 15 degrees to the right. Hypertension was defined as a diastolic
      pressure (Korotkoff phase 4) of 90 mmHg or more. Forty-one percent were
      classified as hypertensive. Hypertension before 33 weeks had a perinatal
      mortality of 264/1000.

PMID- 1976543
TI  - A comparative randomized study of oral prostaglandin E2 (PGE2) tablets and
      intravenous oxytocin in induction of labor in patients with premature rupture of
      membranes before 37 weeks of pregnancy.
AB  - In a randomized prospective study, we compared the use of intravenous oxytocin
      with oral PGE2 tablets for stimulation of labor in cases of premature rupture of
      membranes (PROM) before term, where the onset of spontaneous labor did not occur
      within the first 3 h. This study represents the first of its kind in which oral
      PGE2 and oxytocin have been directly compared as oxytocic agents for PROM before
      37 weeks. Labor induction was successful in 96% of patients in the PGE2 group
      compared with 84% in the oxytocin group. The incidence of cesarean section (CS)
      was 5% and 16% in the PGE2 and the oxytocin groups, respectively. While 10% of
      the CS were performed due to fetal bradycardia in the oxytocin group, none was
      performed in the PGE2 group despite the fact that the latter group had relatively
      lower Bishop scores. The data presented indicate that oral PGE2 is safe and
      effective in initiating active labor in healthy women at pre-term with PROM. Thus
      we recommend its use to induce labor 3 h after rupture of membranes before 37
      weeks gestation.

PMID- 1976545
TI  - A centile chart for weight gain in pregnancy for the urban population of the
      Western Cape, South Africa.
AB  - Weight gain during pregnancy was studied. Women with low body mass index (BMI)
      gained significantly more weight than women with high BMI. Older women gained
      significantly less weight than younger women. Centile charts were constructed
      using a maximum likelihood procedure. The centile charts for patients who are
      less than or equal to 25 years or with a BMI = less than or equal to 24 kg/m2
      cannot be regarded as differing significantly, however the chart for patients
      greater than 25 years with a BMI greater than 24 kg/m2 does lie significantly
      below the others. For practical purposes the process of weight gain can be
      regarded as independent of gestational age. These charts can thus be used without
      knowledge of gestational age.

PMID- 1976544
TI  - Immunological studies on pre-eclampsia in Nigerian women.
AB  - Circulating immune complexes, C3b inactivator, C3 activator, C3c, C4 and C
      reactive protein were assayed in 49 patients with pre-eclampsia and 35 apparently
      healthy pregnant Nigerian women. Pre-eclamptic women had significantly higher
      mean levels of circulating immune complexes, C3c and C-reactive protein. C3
      activator mean level was also higher in pre-eclampsia than in normal pregnancy,
      C3b inactivator concentrations were greatly depressed and the mean level was also
      significantly lower in the pre-eclamptic group (P less than 0.001). However, C4
      mean levels were the same in both groups. From the results, it is postulated that
      in pre-eclamptic conditions the significantly depressed levels of C3b inactivator
      could predispose to the persistence of deposited immune complexes in the kidneys,
      resulting in tissue damage. The findings also generally indicate an immunologic
      pathogenesis for the renal lesions in pre-eclampsia in Nigerian women.

PMID- 1976546
TI  - The prognostic significance of augmentation of urethral closure pressure and
      functional length.
AB  - Sixty-one women with genuine stress incontinence undergoing preoperative and
      postoperative multichannel urodynamic investigation were tested with augmenting
      urethral closure pressure profiles during contraction of the pelvic floor muscles
      to assess voluntary control of the urethral "sphincter." Increases of 20% or more
      above resting functional length and closure pressure were selected as indicators
      of augmentation. The presence or absence of augmentation of functional urethral
      length and/or closure pressure during pelvic floor contraction allowed for the
      grouping of these patients into six subgroups which were compared for urinary
      symptoms, prior anti-incontinence procedures and the presence of low urethral
      pressure, detrusor instability and genuine stress incontinence both pre- and
      postoperatively. Evaluation of the patient's ability to augment functional length
      and closure pressure did not affect surgical success nor did its presence or
      absence correspond to the presence of a low pressure urethra, detrusor
      instability, or specific urinary symptoms. Evaluation of augmentation of
      functional length and closure pressure was therefore felt to be of no prognostic
      value during the performance of multichannel urodynamic testing in incontinent
      females.

PMID- 1976547
TI  - Efficacy of second-look laparotomy for patients with epithelial ovarian
      carcinoma.
AB  - Second-look laparotomies (SLL) were performed on 42 patients with ovarian
      carcinoma. Ten (24%) had residual disease. Serum CA 125 values before SLL
      predicted the presence of residual tumors, but its relatively high false negative
      rate made it unable to take place of SLL. Positive peritoneal cytology at initial
      surgery significantly influenced SLL results in patients with early disease.
      Residual pelvic lesions at initial surgery seemed to resist subsequent
      chemotherapy. Salvage therapy with external pelvic irradiation was effective on
      lesions confined to the pelvis without serious toxicity. Patients with advanced
      disease, undergoing SLL achieved better survival than without SLL. This study
      shows SLL is still the most accurate procedure in assessing the efficacy of
      treatment, and useful in selecting second-line therapy.

PMID- 1976548
TI  - Tumor marker CA 125 level and ovarian volume at different cycle day periods and
      in postmenopause.
AB  - The value of using CA 125 for screening of ovarian carcinoma is still under
      debate. It is important to be aware of possible physiological variation in serum
      levels of this antigen. This study aimed at finding out whether there were any
      differences in CA 125 levels in serum at different cycle day periods of fertile
      women and postmenopausal women. In 106 women, CA 125 and ovarian volume were
      measured at different cycle day periods and in postmenopausal women. The highest
      levels were found in cycle day (CD) 1-9, i.e. 22 units/ml and the lowest in
      postmenopausal women i.e. 6.7 units/ml. No correlation could be found between the
      CA 125 levels and ovarian volume as measured by vaginal sonography.

PMID- 1976550
TI  - Early experience with in vitro fertilization-embryo transfer and gamete
      intrafallopian transfer in a Nigerian hospital.
AB  - We present our early experience with in vitro fertilisation-embryo transfer (IVF
      ET) and gamete intrafallopian transfer (GIFT) in a Nigerian Hospital. Twenty-one
      patients were recruited, 11 patients for the IVF-ET program and 10 for the GIFT
      program. In the IVF program the oocyte recovery rate was 100%, the fertilization
      rate was 66% and the cleavage rate was 97% but no live pregnancies were achieved.
      In contrast, one live delivery was achieved with GIFT. These results suggest that
      both IVT-ET and GIFT are feasible in developing countries.

PMID- 1976549
TI  - Cervical dilatation with Lamicel in first trimester therapeutic abortion.
AB  - Preoperative treatment with Lamicel tent for first trimester therapeutic abortion
      was evaluated in an open randomized trial and compared with no treatment.
      Measured by the lowest Hegar moved through the internal os without resistance,
      the Lamicel group had significantly higher cervical dilatation than the control
      group (8.2 mm vs. 5.8 mm; P less than 0.001). One perforation was observed in the
      Lamicel (n = 270) group compared to six in the control group (n = 359) (not
      significant). There was no difference between the groups in the frequency of
      readmissions to the hospital. During one year of clinical experience with
      pretreatment of elective abortion with Lamicel per- and postoperative
      complication rates were not reduced.

PMID- 1976551
TI  - Pregnancy and complicated familial Mediterranean fever.
AB  - Familial Mediterranean Fever (FMF) is an inherited disease, closely following the
      pattern of autosomal recessive inheritance. Amyloidosis is the most severe
      complication of the disease. The prevalence of pregnancy loss in women with FMF
      is considered to be high. There is no information to support the possibility of
      increase risk of late pregnancy complications or change in the natural course of
      the disease. Two cases are presented with complicated FMF. One case with proved
      amyloidosis and the second patient with ascites. Pregnancy and neonatal outcome
      were uneventful in both. No further deterioration in the systemic disease
      occurred.

PMID- 1976552
TI  - Unusual presentations of genital tract tuberculosis.
AB  - Three cases of genital tract tuberculosis (GTB) are described. This disease is
      uncommon in developed countries. Patients may present with infertility, non
      specific menstrual disturbance, pain or abdominal distention. The genital tract
      is usually infected by hematogenous spread from a distant focus, with the
      fallopian tubes most commonly involved. Diagnosis is often made retrospectively,
      and once confirmed medical management is the mainstay of treatment. Future
      fertility is doubtful in these patients.

PMID- 1976553
TI  - Breech vaginal delivery after one cesarean section: a retrospective study.
AB  - This retrospective study evaluates the prospects of allowing a vaginal breech to
      follow a previous lower segment cesarean section by examining data from Farwania
      Hospital, Kuwait where 33 (38.4%) of 86 patients with a previous cesarean section
      with fetuses in breech presentation were given a chance for vaginal delivery. The
      remaining 53 patients were delivered by lower segment cesarean section. Out of 53
      patients, 34 patients were sectioned because of the presence of uterine scar. The
      other 19 patients were sectioned because of the additional presence of other
      obstetric complications such as diabetes, pre-eclamptic toxemia or large fetus.
      This group of patients was excluded from comparison.

PMID- 1976555
TI  - Clonal analysis of segmental and compartmental homoeotic transformations in
      polycomb mutants of Drosophila melanogaster.
AB  - We describe two new effects of Polycomb mutations on the determination of
      compartments in the wing of Drosophila. Ventral and posterior wing compartments
      are transformed partially to their dorsal and anterior counterparts. Although
      these new phenotypes are most strongly expressed in lethal pharate adults
      heteroallelic for Pc2 and a new allele PcT2, they are also found regularly but
      with low expressivity as dominant phenotypes of all the other Pc alleles we
      tested. Several different intersegmental homoeotic transformations caused by
      Polycomb have previously been described, leading to the hypothesis that Polycomb
      regulates the activity of certain selector genes normally active in specific
      segments. We now show that the degree of expression of the inter- and
      intrasegmental transformations are highly correlated in a range of different Pc
      genotypes, and that more than one determinative decision can be affected in a
      single compartment. This suggests that the wild-type Pc product may act as a
      general regulator of several different selector genes so as to influence both
      early embryonic and later determinative decisions in the imaginal discs. To test
      this idea we used clonal analysis to look at the effects of Pc on clonal
      restrictions at the dorsoventral and anterioposterior compartment boundaries, and
      its time of action with respect to each phenotype.

PMID- 1976554
TI  - Cloning of rat lutropin (LH) receptor analogs lacking the soybean lectin domain.
AB  - cDNAs coding for rat ovarian luteinizing hormone receptor analogs lacking three
      of the leucine repeats were detected in a library which had been prepared from
      rat luteal tissue undergoing human chorionic gonadotropin-induced luteinization.
      These leucine repeats correspond to amino acids 206-267 and contain the portion
      of the receptor that is homologous to the soybean lectin. The cDNA library also
      contained a receptor analog lacking amino acids 321-700 which code for the
      transmembrane domain. S-1 mapping suggests that this latter form constitutes
      approximately half of all receptor-related mRNA.

PMID- 1976556
TI  - Transiently catecholaminergic (TC) cells in the bowel of the fetal rat:
      precursors of noncatecholaminergic enteric neurons.
AB  - Experiments were done to study the fate of transient catecholaminergic (TC) cells
      that develop in the rodent gut during ontogeny. When they are first detected, at
      Day E11 in rats, TC cells are distributed along the vagal pathway, in advance of
      the descending fibers of the vagus nerves, and in the foregut. The early TC cells
      coexpress the immunoreactivities of several neural markers, including 150-kDa
      neurofilament protein, peripherin, microtubule associated protein (MAP) 5, and
      growth-associated protein (GAP)-43, with those of the catecholamine biosynthetic
      enzymes tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH). All cells
      in the fetal rat bowel at Day E11 that express neural markers also express TH
      immunoreactivity. The primitive TC cells also express the immunoreactivities of
      neural cell adhesion molecule (N-CAM), neuropeptide Y (NPY), and nerve growth
      factor (NGF) receptor (and NGF receptor mRNA). By Day E12 TC cells are found
      along the vagal pathway and throughout the entire preumbilical bowel. At this age
      TC cells acquire additional characteristics, including MAP 2 and synaptophysin
      immunoreactivities and acetylcholinesterase activity, which indicate that they
      continue to mature as neurons. In addition, TC cells of the rat are immunostained
      at Day E12 by the NC-1 monoclonal antibody, which in rats labels multiple cell
      types including migrating cells of neural crest origin. Despite their neural
      properties, at least some TC cells divide and therefore are neural precursors and
      not terminally differentiated neurons. At Day E10 TH mRNA-containing cells were
      not detected by in situ hybridization; however, by Day E11 TH mRNA was detected
      in sympathetic ganglia and in scattered cells in the mesenchyme of the foregut
      and vagal pathway. At this age, the number of enteric and vagal cells containing
      TH mRNA is about 30% less than the number of cells containing TH immunoreactivity
      in adjacent sections. The ratio of TH mRNA-containing cells to TH-immunoreactive
      vagal and enteric cells is even less at Day E12, especially in more caudal
      regions of the preumbilical bowel. A similar decline in the ratio of TH mRNA
      containing to TH-immunoreactive cells was not observed in sympathetic ganglia.
      After Day E12 TH mRNA cannot be detected in enteric or vagal cells by in situ
      hybridization; nevertheless, TH immunoreactivity continues to be present through
      Day E14. DBH, NPY, and NGF receptor immunoreactivities are expressed by TH
      immunoreactive transitional cells in the fetal rat gut after TH mRNA is no longer
      detectable.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1976557
TI  - Polymorphisms of HepG2/erythrocyte glucose-transporter gene. Linkage
      relationships and implications for genetic analysis of NIDDM.
AB  - To assess the contribution of the HepG2/erythrocyte glucose-transporter (HepG2
      GT) gene to the inherited susceptibility to non-insulin-dependent diabetes
      mellitus (NIDDM), cDNA and genomic probes were used to search for restriction
      endonuclease polymorphisms at this locus. Analysis of DNA from 16 unrelated Black
      American individuals with 19 enzymes and as many as six different probes, defined
      four polymorphisms over a 45-kilobase region. Nucleotide diversity (pi = 0.006)
      was low relative to that at other loci, with an average of 1 in 1700 base pairs
      different between two chromosomes at this locus. The observed combined
      heterozygosity for these four sites was 0.69, which indicates that the markers at
      this locus could be useful for linkage analysis in families. Linkage
      disequilibrium values between the four polymorphisms were evaluated by pairwise
      analysis and extended haplotypes. Calculating pairwise associations by the
      disequilibrium statistic delta or by another measure of disequilibrium, D' (the
      maximum likelihood of disequilibrium, which is less dependent on frequency),
      significant linkage disequilibrium could not be demonstrated. However, the
      frequencies of the observed extended haplotypes were shown to differ (chi 2 =
      9.1, df = 2, P less than 0.025) from predicted frequencies if the sites were in
      linkage equilibrium in Blacks. The frequencies of these four polymorphisms were
      determined in Black nondiabetic (n = 44) and NIDDM (n = 63) subjects. Neither the
      allelic nor genotypic frequencies of the polymorphisms differed between the two
      groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1976558
TI  - Fasting and postprandial concentrations of somatostatin-28 and somatostatin-14 in
      type II diabetes in men.
AB  - Recent evidence suggests that somatostatin-28 (SRIF-28), cleaved from
      prosomatostatin by cells of the upper intestine, acts as a nutrient-stimulated
      inhibitor of insulin secretion in healthy men. A role for SRIF-28 in the
      pathophysiology of diabetes has not been previously explored, although several
      groups have measured circulating somatostatinlike immunoreactivity (SLI) in
      diabetic subjects. To investigate the possible mediation of abnormal insulin
      secretion in diabetes by SRIF-28, plasma levels were measured in 10 non-insulin
      dependent diabetic men and 9 age- and weight-matched control subjects.
      Concentrations of SRIF-14 and SLI were also obtained. Subjects were admitted for
      study after an overnight fast, blood was collected before and at 30-min intervals
      for 4 h after a fat meal, and plasma samples were analyzed for SRIF-28 and SRIF
      14 by specific methods. Basal glucose levels in the diabetic men were
      significantly higher than in control subjects (10.2 +/- 1 vs. 5.8 +/- 0.2 mM),
      but insulin levels were similar (79 +/- 14.2 vs. 93.3 +/- 14.2 pM). The diabetic
      men had significantly lower basal SRIF-28 levels than the control subjects (11.4
      +/- 0.6 vs. 14.6 +/- 1.0 pM, P = 0.017). After fat intake, SRIF-28 levels
      throughout the 4 h of study were indistinguishable in the two groups (270 vs.
      292% of basal). Basal SRIF-14 and SLI levels were not significantly different in
      the two groups, and SRIF-14 and SLI concentrations rose similarly after the meal.
      There were no correlations between basal SRIF-28 and glucose or insulin
      levels.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1976559
TI  - Increased sensitivity to insulin-releasing and glucoregulatory effects of
      dynorphin A1-13 and U 50488h in ob/ob versus lean mice.
AB  - The effects of two kappa-opiate agonists, U 50488h and dynorphin A1-13, on plasma
      insulin and glucose concentrations in vivo and insulin release in vitro were
      tested in fasted genetically obese (ob/ob) and lean (+/+) mice at 12-15 wk of
      age. Fasting plasma insulin concentrations in ob/ob and lean mice were 1.22 +/-
      0.10 and 0.23 +/- 0.05 nM, and plasma glucose levels were 6.90 +/- 0.84 and 4.70
      +/- 0.29 mM, respectively. Administration of U 50488h (1 mg/kg body wt i.p.) to
      ob/ob mice dramatically raised plasma insulin by 670 and 790 pM at 15 and 30 min.
      Plasma glucose was raised from 5 min onward to a maximum increment of 4.2 mM
      above baseline. These effects were blocked by simultaneous administration of
      naloxone (10 mg/kg). A higher dose of U 50488h (10 mg/kg body wt i.p.) was
      required to produce significant increases in lean mouse plasma insulin (81 pM at
      15 min) and glucose (0.7, 1.1, and 1.7 mM at 5, 15, and 30 min, respectively).
      Dynorphin (1 mg/kg body wt i.p.) raised plasma insulin in ob/ob mice by 380 and
      410 pM at 15 and 30 min and raised plasma glucose by 1.6 mM at 15 min. In lean
      mice, the same dose of dynorphin had no effect on plasma insulin concentrations
      but induced a small rise in glucose. In ob/ob mice, the agonist-induced rise in
      glucose did not cause the insulin response, because insulin levels were not
      elevated by a glucose challenge.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1976560
TI  - Distribution of somatostatin-14 and somatostatin-28 gastrointestinal-pancreatic
      cells of rats and humans.
AB  - Somatostatin-14 and somatostatin-28 are biologically active peptides derived from
      the posttranslational cleavage of prosomatostatin. Because both peptides are
      found in variable concentrations in the gastrointestinal (GI) tract and pancreas,
      it has been contended that somatostatin-28 is either an intermediate in the
      processing to somatostatin-14 or a terminal product derived from prosomatostatin.
      To address this question, two antisera were used to recognize epitopes in two
      regions of somatostatin-14; one with high specificity for somatostatin-14 and the
      other interacting with prosomatostatin, somatostatin-28, and somatostatin-14.
      Distribution of these peptides was measured in extracts of pancreas and mucosa
      and submucosa/muscularis from the rat and human GI mucosal biopsies; the antisera
      were used to immunostain cells in these tissues. Extracts of human and rat
      intestinal mucosa contained both somatostatin-28 and somatostatin-14. By
      immunocytochemistry, D cells in stomach and pancreas and neural processes in the
      intestine, extending into the mucosal villi adjacent to endocrine cells, stained
      with both antisera indicating the presence of somatostatin-14, prosomatostatin,
      and possibly somatostatin-28. In contrast, endocrine cells in the gut reacting
      with antisera against somatostatin-28 did not immunostain with somatostatin-14
      specific antisera. Thus, these data suggest that somatostatin-28 is the terminal
      peptide processed from prosomatostatin in intestinal mucosal cells, whereas
      somatostatin-14 is the major final product in gastric and pancreatic D cells and
      neurons. The localization of somatostatin-28 and somatostatin-14 in different
      cells in the pancreas and GI tract implies that they serve different functions.

PMID- 1976561
TI  - Role of gastrin in bombesin-stimulated somatostatin release.
AB  - The intermediary pathways in the bombesin-induced somatostatin release were
      examined in isolated perfused rat stomach obtained from male rats that were
      fasted overnight. The stomachs were perfused by way of the celiac artery. On
      coinfusion of 1.0 mumol/L tetrodotoxin and 1 nmol/L bombesin, a significant
      depression in release of somatostatin was observed compared with that observed
      with bombesin alone. The 5-minute integrated somatostatin response after
      treatment with tetrodotoxin and bombesin was 173% +/- 14% of basal, which was
      significantly lower than that observed with bombesin alone (394% +/- 59% of
      basal, P less than 0.05) but significantly higher than that observed with medium
      199 alone (95% +/- 7% of basal, P less than 0.05); this indicated that
      approximately 70% of the bombesin-stimulated somatostatin release was indirectly
      mediated through neural pathways, while a significant (approximately 30%) segment
      of it was mediated by nonneural mechanisms. To test if the 30% somatostatin
      release was secondary to gastrin release in response to bombesin, gastrin
      antiserum and bombesin (1 nmol/L) were coadministrated in the presence or absence
      of tetrodotoxin (1 mumol/L). Gastrin antiserum alone did not significantly affect
      basal release of somatostatin but caused a significant inhibition (approximately
      23%) of bombesin-provoked somatostatin release. Coadministration of gastrin
      antiserum and tetrodotoxin attenuated bombesin-stimulated somatostatin release.
      Gastrin (1 mumol/L) alone significantly stimulated somatostatin release (150% +/-
      10% of basal), which was completely attenuated in the presence of gastrin
      antiserum. Tetrodotoxin did not affect bombesin-elicited gastrin release,
      confirming that bombesin-stimulated gastrin release was directly mediated. To
      determine the nature of the neural pathways mediating the bombesin-induced
      somatostatin release, atropine (100 nmol/L) was used. Atropine inhibited bombesin
      induced somatostatin release to the same extent as tetrodotoxin, indicating that
      cholinergic pathways mediated bombesin-induced somatostatin release. These
      results show that almost all the somatostatin response to bombesin is indirectly
      mediated, and is composed of a major neural (cholinergic) and a minor nonneural
      pathway. The nonneural mechanism appears to be contributed primarily by gastrin
      released in response to bombesin, which apparently has a short paracrine positive
      feedback effect on somatostatin release.

PMID- 1976564
TI  - Somatostatin for variceal bleeders.

PMID- 1976562
TI  - Long-term 6-mercaptopurine treatment in adolescents with Crohn's disease.
AB  - Although 6-mercaptopurine is often used to treat adolescents with intractable
      Crohn's disease, its long-term efficacy has not yet been studied in this
      population. This study shows data derived from 36 adolescents (mean age +/- SD,
      16.5 +/- 3.3 years; 27 males, 9 females) treated at least 6 months with 6
      mercaptopurine (1.5 mg.kg-1.day-1, maximum of 75 mg/day). Sites of Crohn's
      disease at the start of 6-mercaptopurine therapy included 17 ileocolic, 9
      pancolic, 7 small bowel, and 3 partial colon. All had received corticosteroids,
      sulfasalazine, antibiotics, and nutritional support for 5.0 +/- 3.0 years before
      administering 6-mercaptopurine, but intractable symptoms persisted. Disease
      activity lessened during the first year of 6-mercaptopurine, reflected by a
      higher Lloyd-Still disease activity score (pre, 64 +/- 9 vs. 6-mercaptopurine, 72
      +/- 11; P less than 0.0001). General activity, physical examination, nutrition,
      and laboratory subscores all improved (P less than 0.004). Lessened disease
      activity occurred despite concomitant decrease in duration of prednisone use
      (pre, 9.5 +/- 4.2 vs. 6-mercaptopurine, 6.6 +/- 4.9 months/year; P less than
      0.001) and cumulative annual prednisone exposure (pre, 3672 +/- 2106 vs. 6
      mercaptopurine, 1964 +/- 1460 mg; P less than 0.0007). The frequency of perianal
      fistulae and abscesses also decreased (P less than 0.01) during treatment. Annual
      rates of hospitalization decreased in 44% of subjects during 6-mercaptopurine
      treatment, while increasing in only 22%. Follow-up beyond 1 year of 6
      mercaptopurine treatment showed continued remission in 23 of 30 subjects. No
      serious complications were seen. 6-mercaptopurine is an effective long-term
      therapy for adolescents with intractable Crohn's disease. While inducing
      remission, it also has a significant steroid-sparing effect which may be of
      particular benefit to this population.

PMID- 1976563
TI  - Randomized, double-blind, placebo-controlled trial of somatostatin for variceal
      bleeding. Emergency control and prevention of early variceal rebleeding.
AB  - A randomized, double-blind, placebo-controlled trial of somatostatin was
      conducted among 120 patients admitted for bleeding esophageal varices (59
      placebo, 61 somatostatin). An initial 250-micrograms bolus of somatostatin
      followed by a 5-day continuous infusion of 250 micrograms/h and an identical
      administration of placebo were evaluated for both the control of bleeding and
      prevention of early rebleeding from varices. Failure to control bleeding occurred
      in 22 (36%) somatostatin patients vs. 35 (59%) placebo patients, with time to
      failure occurring earlier with placebo (P = 0.036). blood and plasma transfused
      per hour during drug infusion of trial drug was reduced in the somatostatin
      group: median 0.033 vs. 0.105 unit/h (P = 0.025). Use of balloon tamponade was
      halved in somatostatin-treated patients. The average effect of somatostatin was a
      41% reduction in the hazard of failure (95% confidence interval, -1% to 65%, P =
      0.0545) after adjustment for the severity of liver disease, which was the only
      other variable having a significant influence on time to failure. There was no
      difference in 30-day mortality per admission (7 placebo, 9 somatostatin) or
      complications. It is concluded that somatostatin is safe and more effective than
      placebo for the control of variceal bleeding.

PMID- 1976566
TI  - Anaphylaxis.

PMID- 1976565
TI  - Isolation of nucleotide activated amino acid and peptide precursors of the
      pseudomurein of Methanobacterium thermoautotrophicum.
AB  - The following putative precursors of the pseudomurein were isolated from
      trichloroacetic acid extracts of Methanobacterium thermoautotrophicum: a uridine
      diphosphate activated derivative of glutamic acid and the uridine diphosphate
      activated peptides (see text). The activated glutamic acid residue and the three
      activated pepetides lack the glycan components N-acetylglucosamine and N
      acetyltalosaminuronic acid present in the intact pseudomurein. In this case
      uridine diphosphate should be directly linked to the amino group of a glutamic
      acid residue, which represents a new mode of amino acid and peptide activation.

PMID- 1976567
TI  - Mild asthma.

PMID- 1976568
TI  - Region-specific recombination and expression are directed by portions of the
      Drosophila engrailed promoter.
AB  - The Drosophila engrailed gene is expressed in the cells of the posterior
      developmental compartments. To investigate how the engrailed gene is regulated,
      chimeric genes consisting of fragments of the engrailed promoter and Escherichia
      coli lacZ were incorporated into the Drosophila germ line by P-element-mediated
      recombination. Fusion constructs with 7.5 kb of 5'-flanking sequence contain
      sufficient information to promote expression in most of the embryonic, larval,
      and imaginal posterior compartments; transformants with smaller fragments of the
      5' region do not. Remarkably, of 20 independent transformants with constructs
      containing more than 1 kb of 5'-flanking DNA, 7 integrated in or around the
      engrailed locus. These strains inactivate engrailed function to varying degrees,
      and some express lacZ with a position- and temporal-specific program that is
      indistinguishable from the normal engrailed gene. Presumably, in these strains,
      lacZ is expressed in the context of the engrailed promoter.

PMID- 1976570
TI  - Mutations in the Drosophila gene extradenticle affect the way specific homeo
      domain proteins regulate segmental identity.
AB  - We characterized a gene, extradenticle, which seems to interact with a specific
      subset of Drosophila homeo domain proteins, possibly affecting their target
      specificity. This interpretation is based on an examination of the zygotic and
      maternal effect phenotypes of extradenticle mutations. In embryos with reduced
      levels of extradenticle gene product, anterior and posterior segmental
      transformations occur. Segmental identity in Drosophila is mediated by the
      products of the Antennapedia and bithorax complexes. These homeo domain proteins
      are thought to regulate different target genes specifically in each segment,
      resulting in different morphologies. extradenticle alters segmental identity
      without affecting the pattern of expression of homeotic genes. Genetic tests
      demonstrate that in extradenticle mutants, the homeotic proteins are functional
      and act in their normal segmental domains, yet segmental identities are altered.
      Even when homeotic proteins are ectopically expressed under the control of a
      heterologous promoter, extradenticle mutations affect their consequences. Thus,
      in the absence of sufficient extradenticle product, altered segmental morphology
      results from alteration of the functional consequences of specific homeo domain
      proteins, possibly through alterations in their target gene specificity.
      extradenticle is also expressed maternally. Complete removal of extradenticle,
      maternally and zygotically, leads to specific alterations in segmentation, many
      of which result from failure to maintain the expression of the homeo domain
      protein engrailed.

PMID- 1976569
TI  - RNA pseudoknot domain of tobacco mosaic virus can functionally substitute for a
      poly(A) tail in plant and animal cells.
AB  - The genomes of many RNA viruses terminate in a tertiary structure similar to the
      L-conformation of tRNAs and this structure is recognized by many tRNA-specific
      enzymes such as aminoacyl-tRNA synthetase. Virtually the entire 3'-untranslated
      region (UTR) of tobacco mosaic virus (TMV) RNA is involved in an extended
      tertiary structure containing, in addition to a tRNA-like structure, a pseudoknot
      domain that lies immediately upstream. Although the functions of these structures
      are not well understood, they are essential to the virus. We demonstrate that the
      addition of the 204-base TMV 3'-untranslated region to foreign mRNA constructs
      can increase gene expression up to 100-fold compared to nonadenylated mRNA. The
      3'-UTR of TMV was equal to or greater than a polyadenylated tail in enhancing
      gene expression in electroporated dicot and monocot protoplasts. The TMV 3'-UTR
      is functionally similar to a polyadenylated tail in that it increases mRNA
      stability and translation and must be positioned at the 3' terminus to function
      efficiently. Similar effects on expression were observed in Chinese hamster ovary
      cells, demonstrating that the sequence functions in a wide range of eukaryotes.
      When the extended tertiary structure was dissected, the upstream pseudoknot
      domain was found to be largely responsible for increasing expression. The
      inclusion of the tRNA-like structure, however, was important for full regulation.

PMID- 1976572
TI  - Tales of poly(A): a review.
AB  - Until recently, evidence to support a translational role for the 3'-poly(A) tract
      of eukaryotic mRNAs has been mostly indirect, including: a correlation between
      the adenylation status of individual mRNAs and their translatability in vivo or
      in vitro, the demonstration that exogenously added poly(A) is a potent
      competitive inhibitor of the translation of poly(A)+mRNA, but not poly(A)-mRNAs
      in vitro, and a correlation between the abundance and stability of poly(A)
      binding proteins (PABPs) and the rate of translational initiation in vivo.
      However, more recent studies demonstrate directly that poly(A)+mRNAs can initiate
      translation more efficiently than poly(A)-mRNAs, and indicate that this effect
      is: (i) targeted to the formation of 80S initiation complexes, and (ii) likely to
      be mediated by the cytoplasmic PABP. We suggest that the 3'-poly(A) tail should
      be considered a translational enhancer which may stimulate translational
      initiation in much the same way that transcriptional enhancers are thought to
      stimulate transcriptional initiation.

PMID- 1976571
TI  - Analysis of the ftz upstream element: germ layer-specific enhancers are
      independently autoregulated.
AB  - The Drosophila fushi tarazu (ftz) upstream element is an enhancer-like element
      that is required for the correct expression of ftz in developing embryos and that
      directs transcription from a minimal promoter in a ftz-like seven-striped
      pattern. Using a deletion analysis, we have identified several independent cis
      regulatory elements in the upstream element. A distal enhancer directs fusion
      gene expression in seven stripes primarily in the mesoderm. A more complex
      proximal enhancer contains a mesodermally active element and a second element
      with which it interacts to generate seven stripes in the ectoderm. Striped
      expression directed by each enhancer is ftz-dependent, and each contains binding
      sites for purified ftz homeo domain. We suggest that ftz protein acts in
      combination with germ layer-restricted transcription factors directly and
      positively to regulate the transcription of its own gene.

PMID- 1976573
TI  - Characterisation of the alleles encoding ovine beta-lactoglobulins A and B.
AB  - beta-Lactoglobulin (BLG) is the major whey protein in the milk of ruminants and
      is produced in the mammary gland during pregnancy and lactation. Here, we compare
      the nucleotide sequences of two BLG-encoding clones isolated from a sheep genomic
      library. The two clones are very similar differing by only 1 bp in their coding
      regions, giving rise to a Tyr/His difference in the gene product, and suggesting
      that the two clones correspond to A and B allelic variants of BLG. The
      isoelectric points (pI) of BLGs A and B were estimated as 5.7 and 6.0,
      respectively. Transgenic mice carrying a particular clone secrete BLG of the
      expected pI into their milk. Restriction fragment length polymorphism analysis of
      a small sheep population demonstrated the existence of at least four BLG
      haplotypes.

PMID- 1976575
TI  - [Quality of work of operators during heat-induced discomfort].

PMID- 1976574
TI  - Identification of an unusual deletion within homologous repeats of human
      reticulocyte beta-spectrin and probable peptide polymorphism.
AB  - We screened two different human reticulocyte cDNA libraries with beta
      spectrin(beta Sp)-specific polyclonal antibodies and with our original
      radiolabeled human BSP cDNA probe (encoding beta Sp). Of the 20 independent
      clones, the largest had about a 2.5-kb insert corresponding to the deduced amino
      acid (aa) sequence of the beta-7 to beta-14 repetitive segments. Among these
      segments, segment 12 was 7 aa shorter than the other repetitive segments. We
      showed that this truncation was not a result of (i) cloning artifact, (ii)
      alternate splicing, or (iii) common genomic polymorphism by additional
      examination of 14 individual human chromosomes. Recently, another laboratory
      described the BSP nucleotide (nt) sequence overlapping partially with our
      sequence. These overlapping sequences were homologous with the exception of two
      nt differences at the positions 1342 and 1514. The discrepancy at nt 1342 changes
      the His to Arg. This newly derived probe has been used to find an additional
      example of BSP restriction fragment length polymorphism.

PMID- 1976577
TI  - Intragastric acidity and serum gastrin after sufotidine.

PMID- 1976578
TI  - [Control of spinal motor system by descending noradrenergic neuron].
AB  - The physiological function of the descending noradrenergic system in the spinal
      ventral horn has not yet been fully elucidated. Here we describe our recent
      findings showing the motor function of the noradrenergic fibers. 1) alpha 1
      Antagonists and alpha 2-agonists depressed the spinal mono- and polysynaptic
      reflex potentials in rats that have an intact connection between the spinal cord
      and the brain. In rats spinalized at the Cl level, the alpha 1-agonistic action
      of adrenergic agents increased the spinal reflexes. 2) In the radio frequency
      lesioned decerebrate rigidity model of rats, alpha 1-antagonists and alpha 2
      agonists reduced the rigidity by affecting the spinal and supraspinal levels,
      respectively. 3) alpha 2-Agonists but not alpha 1-antagonists reduced
      noradrenaline released into the subarachnoid space of anesthetized rats. 4) In a
      slice preparation isolated from adult rats, the alpha 1-agonistic action of
      adrenergic agents increased the excitatory synaptic transmission of the ventral
      horn. Thus, it was demonstrated that alpha 2-agonistic action at the brain stem
      inhibited spinal motor activity by reducing the release of noradrenaline in the
      spinal cord, and that the facilitatory action through alpha 1-adrenoceptors was
      dominant in descending noradrenergic transmission in the motor nuclei of the
      ventral horn.

PMID- 1976576
TI  - Inhibition of cell mediated cytotoxicity by sulphasalazine: effect of in vivo
      treatment with 5-aminosalicylic acid and sulphasalazine on in vitro natural
      killer cell activity.
AB  - Decreased cell mediated cytotoxicity occurs frequently in inflammatory bowel
      disease, particularly in patients with active disease. It is not clear, however,
      whether this decrease is caused by the disease or is a consequence of the medical
      treatment. In this study we evaluated the effect of in vivo treatment with 5
      aminosalicylic acid and sulphasalazine on the in vitro natural killer cell
      activity in five patients with inflammatory bowel disease in remission and in
      four healthy control subjects in a double blind randomised crossover trial
      preceded and separated by four weeks of treatment with placebo. The natural
      killer cell activity was significantly impaired in 67% (six of nine subjects)
      after four weeks' sulphasalazine treatment and tended to be related to subjects
      with a slow acetylator phenotype. In contrast, 5-aminosalicylic acid treatment
      caused only a marginal reaction in the natural killer cell activity in 22% (two
      of nine subjects). The inhibitory effects were found to be reversible since the
      decreased natural killer cell activity was completely restored after placebo
      treatment in all subjects. In conclusion, in vivo treatment with sulphasalazine
      inhibits the in vitro natural killer cell activity and this seems to be mediated
      by the sulphapyridine moiety. This phenomenon may contribute to the low natural
      killer cell activity found in patients with active inflammatory bowel disease.

PMID- 1976579
TI  - The influence of artificial colonization with E. coli strain O83 on the
      intestinal flora in infants.
AB  - Dominant bacterial strains present in stool (with particular emphasis on E. coli
      strains) were examined in 4 groups of healthy infants: breast-fed and bottle-fed,
      colonized with E. coli O83, and control (non-colonized) breast-fed and bottle-fed
      newborns. The presence of fimbriae was examined by hemagglutination, the P
      fimbriae-bearing strains were tested by the PPA latex test. In addition,
      adherence to cell line HT-29 and serotyping was performed in selected strains.
      The E. coli strain O83 was found to possess type 1 fimbriae. Fewer bacterial
      strains possessing type 1 fimbriae were found in E. coli O83-colonized infants
      (except the O83 serotype) than in control infants. The E. coli O83 strain
      colonized significantly better the breast-fed than the bottle-fed infants; its
      higher adherence activity was demonstrated even in cell line HT-29. Finally,
      colonization with E. coli O83 influenced the character of microbial intestinal
      flora: the frequency of positive E. coli isolates was significantly higher in
      colonized (both breast- and bottle-fed) than noncolonized infants.

PMID- 1976581
TI  - Continuing advances in H2-antagonist therapy: focus on famotidine. Proceedings of
      a symposium. Nice, France, 14 October 1989.

PMID- 1976582
TI  - Gastroesophageal reflux: clinical diagnosis, current therapy, future trends.
AB  - In the usual clinical setting, symptomatic gastroesophageal reflux can be equated
      with heartburn; however, the diagnosis of gastroesophageal reflux disease (GERD)
      can be obscure. Recent improvements in the quality of fiberoptic endoscopy along
      with other imaging and diagnostic techniques have permitted a more complete
      understanding of the pathophysiology of gastroesophageal reflux. The continued
      development of antisecretory, prokinetic, and mucosal protective agents allows
      the gastroenterologist a choice of effective therapeutic approaches to deal with
      contributing factors such as gastric acid secretion, lower esophageal sphincter
      pressure, or gastric motility. Although standard doses of potent H2-receptor
      antagonists are the focus of current reflux disease therapy, increasingly
      aggressive regimens will probably become available for refractory patients.

PMID- 1976580
TI  - Effects of combined use of roxatidine and pirenzepine on gastric secretion in
      humans.
AB  - We examined the effects of the combined use of H2-receptor antagonist
      (roxatidine) and muscarinic receptor antagonist (pirenzepine) by oral
      administration on gastric juice and acid secretion in humans. The volume, pH
      level, and acidity of gastric juice were determined in the sample collected at
      9:00 AM 10 hr after either the oral administration of 150 mg of roxatidine or the
      combined administration of 150 mg of roxatidine and 50 mg of pirenzepine.
      Significant decrease in volume and acidity and increase in pH were observed in
      both roxatidine group and combined group compared with control placebo group, but
      significant difference were not observed in gastric pH and acidity between
      roxatidine group and combined group. The volume of gastric juice was decreased
      significantly by the combined administration in comparison with the sole
      administration of roxatidine. Consequently, the combined oral administration of
      the two agents was considered to be more effective than the sole administration
      of roxatidine for clinical cases which require stronger suppression of gastric
      secretion at the night.

PMID- 1976583
TI  - Acid secretion and acid suppression in pathogenesis and healing of peptic ulcer
      disease.
AB  - Numerous environmental and genetic factors have been implicated in the
      pathogenesis of peptic ulcer disease. Although the cause of this disorder has not
      been established, acid pepsin has been acknowledged at least as a permissive
      factor in its development. More important, inhibition of nocturnal or 24-hour
      intragastric acidity is predictably associated with ulcer healing. Famotidine 40
      mg at bedtime maintains approximately one-third of pH readings at or above 3.5,
      reduces pepsin activity, and has no adverse effect on mean total serum gastric
      concentrations after one week of therapy. In addition, the effect of this dose of
      famotidine is comparable to ranitidine 300 mg at bedtime and predicts comparable
      rates of ulcer healing. Thus, monitoring of intragastric pH levels may be useful
      in identifying potent healers of peptic ulcer disease and in selecting optimal
      doses or timing of drug administration. Studies of famotidine using such
      measurements have suggested that this new H2-receptor antagonist is comparable to
      ranitidine in the healing of duodenal ulcers.

PMID- 1976584
TI  - Problems in assessing pharmacologic treatment of acute upper gastrointestinal
      bleeding.
AB  - Therapeutic effects are plausible, and drugs are widely used to treat hemorrhage
      from peptic ulcers. Available data, however, are inadequate to establish the
      usefulness of pharmacologic measures.

PMID- 1976585
TI  - Neurochemical control of oxyntic cell secretion.

PMID- 1976586
TI  - Physiological regulation and biological function of thyreotropin. International
      symposium. Goslar, June 1989. Proceedings.

PMID- 1976587
TI  - Proceedings of the workshop on Frontiers in Gallstone Formation. Biliary
      cholesterol transport and precipitation. Warrenton, Virginia. April 16-19, 1989.

PMID- 1976588
TI  - Hepatocytes explanted in the spleen preferentially express carbamoylphosphate
      synthetase rather than glutamine synthetase.
AB  - Urea cycle enzymes and glutamine synthetase are essential for NH3 detoxification
      and systemic pH homeostasis in mammals. Carbamoylphosphate synthetase, the first
      and flux-determining enzyme of the cycle, is found only in a large periportal
      compartment, and glutamine synthetase is found only in a small, complementary
      pericentral compartment. Because it is not possible to manipulate experimentally
      the intrahepatic distribution of carbamoylphosphate synthetase and glutamine
      synthetase, we looked for conditions in which explanted hepatocytes would exhibit
      either the carbamoylphosphate synthetase phenotype or glutamine synthetase
      phenotype. In the spleen hepatocytes either settle as individual cells or in
      small agglomerates. The dispersed cells only express the carbamoylphosphate
      synthetase phenotype. Within the agglomerates, sinusoids that drain on venules
      develop. Hepatocytes surrounding the venules stain only weakly for
      carbamoylphosphate synthetase but are strongly positive for glutamine synthetase.
      These observations were made for explanted embryonic hepatocytes (no prior
      expression of either carbamoylphosphate synthetase or glutamine synthetase),
      neonatal hepatocytes (compartments of gene expression not yet established) and
      adult periportal and pericentral hepatocytes.

PMID- 1976589
TI  - Neurobiology of schizophrenic syndromes.
AB  - The development of imaging technologies for investigating the living human brain
      has expanded knowledge about schizophrenia and is providing clues about
      biological factors associated with the disorder. Drawing on these and other
      developments in the last two decades, the authors review selected structural,
      functional, neurochemical, immunological, and infectious factors associated with
      the schizophrenic syndrome. Many of the biological alterations reported have also
      been found in other psychiatric, neurological, and medical conditions; therefore,
      the findings have little specificity for schizophrenia and in fact support the
      heterogeneity of the disorder.

PMID- 1976590
TI  - Neuroendocrine markers in pulmonary adenocarcinomas with signet-ring cells.

PMID- 1976591
TI  - Cystic fibrosis typing with DNA probes and screening for delta F508 deletion in
      families from southern France.
AB  - A sample of 235 individuals from 49 French cystic fibrosis (CF) families with at
      least one living affected child was typed with probes for restriction fragment
      length polymorphisms (RFLPs) known to be linked to the CF gene, and was screened
      for the delta F508 mutation. Using a combination of six probes, 44 out of the 49
      families were sufficiently informative to enable prenatal diagnosis or carrier
      determination. As in many other populations, linkage disequilibrium was found
      between the CF locus and the haplotype B (XV2c: allele 1; KM19: allele 2), which
      accounts for about 78% of CF chromosomes in our families. The delta F508 deletion
      was present in 64.3% of CF chromosomes.

PMID- 1976592
TI  - First analysis of the F508 deletion in cystic fibrosis patients from the GDR.
AB  - Cystic fibrosis (CF) patients (n = 157) from the GDR were analysed for the
      occurrence of the recently discovered 3bp deletion causing CF. About 50% of all
      investigated patients were homozygotes and about 30% heterozygotes for this
      deletion. Of the analysed CF chromosomes from these patients, 62% carry the
      deletion, which is in strong linkage disequilibrium with the KM19 restriction
      fragment length polymorphism allele 2 and the 1/2 XV2c/KM19 haplotype.

PMID- 1976593
TI  - Genotyping of the Spanish cystic fibrosis population at the delta F508 mutation
      site and RFLP linked loci.
AB  - Spanish families (n = 75) with at least one affected cystic fibrosis (CF) child
      were typed for restriction fragment length polymorphisms (RFLPs) by the probes
      XV2c, KM19, and pMP6d-9. These families were also studied at the 508 mutation
      site by the polymerase chain reaction method. We have studied the linkage
      disequilibrium between these markers and the CF mutations, the probable number of
      independent secondary CFX (non-delta F508) mutations, and the genetic differences
      between Spain and Western Europe.

PMID- 1976594
TI  - Molecular data on cystic fibrosis in Bulgaria.
AB  - A group of 42 cystic fibrosis (CF) patients and 80 heterozygote carriers was
      analysed for determining the prevalent CF haplotypes and the frequency of delta
      F508. The "high-risk" haplotype B (XV2c-KM19/1 2) was found in 66% of CF
      chromosomes. The prevalent normal haplotypes were A (1 1) and B (2 1). The
      deletion was detected in 54 CF chromosomes (56%), homozygotes constituting 35% of
      all CF patients. In 88% of cases the mutation was linked to haplotype B, and in
      12% to haplotype D (2 2). Chromosomes that did not have delta F508 were found to
      be evenly distributed among all four XV2c-KM19 haplotypes. The use of restriction
      fragment length polymorphisms and direct detection of the mutation makes 94% of
      CF families fully informative for prenatal analysis.

PMID- 1976595
TI  - The frequency of the delta F508 mutation on cystic fibrosis chromosomes in
      Israeli families: correlation to CF haplotypes in Jewish communities and Arabs.
AB  - We have analysed the distribution of the delta F508 mutation and the haplotypes
      of cystic fibrosis (CF) bearing chromosomes among the Israeli CF population. The
      population was classified according to its ethnic origin and included 3 groups,
      Ashkenazi Jews, Sephardic/Oriental Jews and Arabs. Haplotype B (KM19 allele 2,
      XV2c allele 1) was found to be the predominant haplotype in all groups but in
      each of them the haplotype distribution was different. The delta F508 mutation
      was present in all groups and accounts for 32% of the CF mutations. It was mainly
      associated with the B haplotype but only one third of the CF chromosomes with
      this haplotype carry the delta F508 mutation.

PMID- 1976596
TI  - delta F508 deletion in cystic fibrosis in Italian families.
AB  - In 20 Italian families with cystic fibrosis (CF), restriction fragment length
      polymorphisms were detected by five linked markers; a strong linkage
      disequilibrium is observed between the haplotype B (alleles 2/1 with respect to
      KM19/XV2c) and CF. The frequency of the delta F508 deletion in CF chromosomes of
      this sample is 50%. A significant correlation is found between the absence of the
      delta F508 mutation and pancreatic sufficiency.

PMID- 1976597
TI  - delta F508 frequency and associated haplotypes near the cystic fibrosis locus in
      the Yugoslav population.
AB  - Chromosomes from 19 unrelated Southern Yugoslav families in which cystic fibrosis
      (CF) occurs were analysed for the presence of the delta F508 mutation, using
      polymerase chain reaction amplification followed by dot blot and polyacrylamide
      gel analysis. Of the 38 CF chromosomes, 15 (39.5%) carry the delta F508 deletion.
      Restriction fragment length polymorphism haplotypes for KM19/PstI, XV2c/TaqI and
      J3.11/PstI marker loci were determined and are compared for a total of 34 N and
      37 CF chromosomes.

PMID- 1976598
TI  - Frequency of the cystic fibrosis delta F508 mutation in a large sample of the
      French population.
AB  - We have determined the frequency of the cystic fibrosis (CF) delta F508 mutation
      in a large sample of CF patients originating from different areas of France,
      including the greater Paris, Brittany, Alsace, Lorraine and Rhone-Alpes regions.
      A total of 422 CF chromosomes were studied, and the defect was found to account
      for 75% of the mutant alleles. In the course of the survey, a rare nucleotide
      sequence polymorphism leading to an isoleucine to valine substitution at position
      506 of the CF transmembrane conductance regulator protein has been characterized
      in an unaffected individual. Our data enable the evaluation of the probabilities
      that a chromosome negative for the delta F508 mutation carriers another CF
      defect.

PMID- 1976599
TI  - Close relationships between neopterin and beta-2-microglobulin levels in
      intravenous drug abusers.
AB  - Serum from 36 intravenous drug abusers without acquired immunodeficiency syndrome
      (AIDS) or AIDS-related complex were tested for concentrations of neopterin and
      beta 2-microglobulin. The seroprevalence of human immunodeficiency virus (HIV)
      antibody in this group was 50%. Previous studies of this group showed that the
      HIV antibody positive patients had significant increases in HLA-DR expression on
      peripheral blood lymphocytes and increases in serum soluble CD8 antigen. Both
      neopterin and beta 2-microglobulin concentrations were significantly higher in
      the HIV antibody seropositive patients compared to the seronegative patients (p =
      0.001 and p = 0.005, respectively). A highly significant positive correlation
      between neopterin and beta 2-microglobulin was found for the seropositive
      patients (r = 0.8879, p less than 0.0001) as well as for the entire group (r =
      0.6054, p = 0.0002). Significant positive correlations were also found between
      neopterin or beta 2-microglobulin and the percent DR + T cells and CD8 antigen
      levels, although these correlations were not as significant as that observed
      between neopterin and beta 2-microglobulin. No relationships were found between
      neopterin or beta 2-microglobulin and total CD4 cell concentrations or CD4/CD8
      ratios. These data demonstrate the significant interrelationships between various
      immune activation markers in a population at risk for developing AIDS.

PMID- 1976601
TI  - Modulation of multidrug resistance by verapamil or mdr1 anti-sense
      oligodeoxynucleotide does not change the high susceptibility to lymphokine
      activated killers in mdr-resistant human carcinoma (LoVo) line.
AB  - Two sublines were derived from the colon adenocarcinoma line LoVo, the first one
      was sensitive (LoVo/H) and the second one was made resistant to doxorubicin
      (LoVo/Dx). When tested for susceptibility to lysis by different types of immune
      effectors, LoVo/Dx appeared more sensitive than LoVo/H to the killing of
      CD3+CD5+CD16-, CD3- CD16+)-enriched lymphokine activated killers (LAK) or
      activated macrophages. In order to check whether this effect was due to different
      expression of glycoprotein P170 between the two LoVo sublines (30% vs. 90% of
      positive cells), a pharmacological and genetic modulation of P170 was carried out
      in LoVo cells. Treatment of LoVo/Dx with the calcium channel blocker verpamil
      (VRP), strongly impaired P170 function as evaluated by reduced Dx resistance,
      without affecting the lysability of LoVo/Dx cells by LAKs. Moreover, the
      significant inhibition of P170 expression resulting from the treatment of LoVo/Dx
      with mdr1 anti-sense olideoxynucleotide also failed to change the high lysability
      of LoVo/Dx by LAKs. These results, therefore, indicate that molecules other than
      P170 are involved in the increased lysis of LoVo/Dx subline by immune effectors
      and that down-regulation of the P170 expression or function will not reduce the
      potential effectiveness of cancer chemo-immunotherapy.

PMID- 1976600
TI  - Relationships among tumor responsiveness, cell sensitivity, doxorubicin cellular
      pharmacokinetics and drug-induced DNA alterations in two human small-cell lung
      cancer xenografts.
AB  - In an attempt to understand the underlying cellular/biochemical factors of
      sensitivity/resistance in human small-cell lung cancer (SCLC), 2 SCLC tumor lines
      were compared with respect to tumor responsiveness to drug treatment, cell
      sensitivity, cellular doxorubicin accumulation, and DNA topoisomerase-II-mediated
      DNA cleavage. The tumor lines growing in nude mice with similar growth
      characteristics (doubling time around 10 days) were selected since one (POCI
      tumor) was found to be hypersensitive and the other (POSG tumor) resistant to
      doxorubicin treatment. The pattern of anti-tumor drug response of the doxorubicin
      resistant tumor was atypical (i.e., non-adherent to the well-characterized multi
      drug-resistant phenotype), since it responded to vincristine. The markedly
      different in vivo tumor response reflected the intrinsic cellular sensitivity to
      doxorubicin. No correlation was found between cellular drug accumulation and
      doxorubicin sensitivity following in vitro exposure to the drug. In agreement
      with this observation, the expression of mdr-I gene was undetectable in these
      tumors. Thus, in the POSG tumor, resistance to doxorubicin occurred without
      expression of the P-glycoprotein and reduction of cellular drug accumulation. In
      contrast, the extent of DNA cleavage produced by doxorubicin was markedly higher
      in the doxorubicin-hypersensitive than in the doxorubicin-resistant tumor. These
      results, taken together with previous observations in SCLC cell lines, support
      the important role of DNA topoisomerase-mediated effects in the sensitivity of
      SCLC to doxorubicin.

PMID- 1976602
TI  - The role of enoximone in cardiac failure. Proceedings of a satellite symposium to
      the XIth Congress of the European Society of Cardiology. Nice, France, 13
      September 1989. Proceedings.

PMID- 1976603
TI  - The 6th International Congress on Obesity. Kobe, Japan, 21-26 October 1990.
      Abstracts.

PMID- 1976605
TI  - [Fibrinolytic therapy of acute myocardial infarction and acute lung embolism.
      International symposium, 27-28 April 1990, Frankfurt am Main].

PMID- 1976604
TI  - Bilateral perineal ectopic testes.
AB  - Perineal testicular ectopia is seen very rarely, bilaterality is even more scarce
      and three cases have been reported in the literature. Here we present the fourth
      case with bilateral perineal ectopic testes.

PMID- 1976607
TI  - [2nd International Cancer Symposium. Beijing, 18-20 May 1990].

PMID- 1976606
TI  - [Hemodilution in stroke. Satellite symposium to the First European Stroke
      Conference. Dusseldorf, 12-13 May 1990].

PMID- 1976608
TI  - Effects of silicone oil and hyaluronic acid on cultured human retinal pigment
      epithelium.
AB  - An experimental model was developed to evaluate the effects of several vitreous
      substitutes on human retinal pigment epithelial (RPE) cells. Cultured RPE cells
      were grown into confluent monolayers on semipermeable membranes and nourished
      from the basal side only, while the apical surface was directly and continuously
      exposed to preparations of hyaluronic acid and silicone oil for up to 4 weeks. In
      the silicone oil-treated group, multilayer sheets formed within 2 weeks of
      exposure and incorporation of 3H-thymidine was twice that of controls. Exposure
      of RPE cells to silicone oil and certain preparations of hyaluronic acid resulted
      in a three- to fourfold decrease in cellular polarity, as measured by assaying
      the cell-surface enzyme, gamma-glutamyl transpeptidase. These results suggest
      that a model using cultured RPE-cell monolayers is useful in identifying and
      understanding alterations in ocular tissues triggered by exposure to vitreous
      replacement materials.

PMID- 1976609
TI  - Should competence be coerced?

PMID- 1976610
TI  - SvO2 monitoring: research and clinical applications. Symposium proceedings based
      on the Pre-National Teaching Institute (NIT) Conference held by the American
      Association of Critical-Care Nurses. San Francisco, California, May 20, 1990.

PMID- 1976611
TI  - Standard karyotype of the domestic horse (Equus caballus). Committee for
      standardized karyotype of Equus caballus. The Second International Conference for
      Standardization of Domestic Animal Karyotypes, INRA, Jouy-en Josas, France, 22nd
      26th May 1989.
AB  - The following decisions concerning the banded karyotype of the horse (Equus
      caballus) were made at the second International conference for Standardization of
      Domestic Animal Karyotypes, held at Jouy-en Josas, France, 22nd-26th May 1989:
      (1) numbering of the chromosomes was modified to correspond to an arrangement
      into only two groups (the non-acrocentrics and the acrocentrics) within which the
      autosomes are placed according to length alone; (2) a more compact karyotype
      arrangement was adopted: chromosomes 1 to 5 on the first row, 6 to 10 on the
      second, 11 to 13, and, at the far right, X and Y on the third row, 14 to 19 on
      the fourth row, chromosomes 20 to 25 on the fifth, and 26 to 31 on the sixth row;
      (3) the NOR-bearing horse chromosomes were identified as numbers 1, 28 and 31.

PMID- 1976612
TI  - Associations between restriction fragment length polymorphisms detected with a
      probe for human C4 and allotype of C4B5 allele.
AB  - We studied the fourth component of human complement (C4) allotypes in 58 Japanese
      individuals. The technique of Southern, with C4 and 21-OH cDNA probes, was used
      to examine the genomic DNA of 45 individuals typed for C4 by protein
      electrophoresis. Novel HindIII C4 10- and 5-kb and EcoRI C4 13-Kb restriction
      fragments were identified in each of nine Japanese individuals. The novel
      fragments were different from the previously described C4B long (HindIII 31-kb,
      TaqI 6-kb, BamHI 4.3-kb, and EcoRI 12-kb) and C4B short (HindIII 25-kb, TaqI 5.4
      kb, BamHI 3.5-kb, and EcoRI 15-kb) fragments. All novel HindIII- and EcoRI
      positive individuals carried C4B5, BfS, and HLA-Bw54. Therefore, the fragments
      were characteristic for the C4B5 allele. The C4 region was analyzed to determine
      the restriction sites by single and double digests of uncloned genomic DNA with
      several restriction endonucleases. It is speculated that an insertion gene lies
      between the 3' end of the 21-OH and the 5' end of the C4B genes.

PMID- 1976613
TI  - Complete analysis of HLA-DQB1 polymorphism and DR-DQ linkage disequilibrium by
      oligonucleotide typing.
AB  - HLA class II polymorphism is functionally important in the control of immune
      responses, in transplantation immunology, and in the suceptibility to autoimmune
      diseases. HLA-DQA1 and -DQB1 genes exhibit a larger degree of allelic
      polymorphism than usually recognized by routine serology. We have therefore
      performed an extensive analysis of DQB1 polymorphism by oligotyping. A set of 12
      oligo probes was hybridized on polymerase chain reaction-amplified DNA, thus
      allowing the detection of 12 DQB1 alleles, as demonstrated in homozygous as well
      as in heterozygous individuals. This highly sensitive detection system is
      particularly relevant within the DQw1 specificity where the 7 allelic sequences
      can easily be identified. The DQ-DR linkage disequilibrium was analyzed by
      oligotyping of 80 Caucasoid heterozygous individuals (160 haplotypes), and very
      tight associations were observed between DRB1 and DQB1 alleles. Five DRB1
      alleles, DR-BON, DR4/Dw4 or Dw14, DR7, DRw8.3, and DRw11, however, can be
      associated with different DQB1 alleles. Moreover the DRB1 and DQB1 oligotyping
      analysis performed on 20 randomly chosen DRw8 Caucasoid individuals showed a high
      prevalence of the DRB1*0801-DQB1*0402 haplotype. By combining the analysis of
      allelic variations at DRB1, DRB3, and DQB1 loci, we can detect 33 different DR-DQ
      combinations in our panel of Caucasoid individuals. We now apply DQB1 oligotyping
      on a routine basis for optimal matching of unrelated donors for bone marrow
      transplantation.

PMID- 1976614
TI  - Prospective evaluation of pulmonary function in cancer patients treated with
      total body irradiation, high-dose melphalan, and autologous hematopoietic stem
      cell transplantation.
AB  - Pulmonary function tests (standard vital capacity, SVC; total lung capacity, TLC;
      forced expiratory volume in 1 second-forced vital capacity ratio, FEV1/FVC;
      carbon monoxide transfer factor, DLCO) were prospectively evaluated in patients
      (median age 25 years, 13-52 years; median follow-up 20 months, 6-51 months) with
      Hodgkin's disease (15 patients), non-Hodgkin's lymphoma (9 patients), and
      inflammatory breast cancer (3 patients) treated with sequential high-dose therapy
      comprising the following phases over approximately 2 months: a) cyclophosphamide
      (7 g/m2); b) vincristine (1.4 mg/m2), methotrexate (8 g/m2), and cisplatinum (120
      mg/m2) or etoposide (2 g/m2); c) total body irradiation (TBI; 12.5 gy, 5
      fractions over 48 hours), intravenous melphalan (120-180 mg/m2), and
      transplantation of autologous peripheral blood and/or bone marrow hematopoietic
      stem cells. Within 2 months after transplantation, 12 patients also received 25
      Gy radiotherapy boost to mediastinum and clavicular regions. In vivo dosimetry
      evaluations of fractionated TBI treatments showed that mean radiation dose
      absorbed by lungs was 12.18 Gy (97.4% of TBI dose). Despite such a high radiation
      dose, we observed only transient and subclinical decrease of SVC, TLC, and DLCO.
      The decrease of SVC, TLC, and DLCO was more evident and prolonged in patients
      receiving radiotherapy boost. All parameters progressively recovered to normal
      values within 2 years after transplantation. In contrast, FEV1/FVC remained
      within normal limits in all patients, thus demonstrating the absence of
      obstructive ventilatory changes. In addition, no interstitial pneumonia was
      observed.

PMID- 1976615
TI  - Radiation injury in the human kidney: a prospective analysis using specific
      scintigraphic and biochemical endpoints.
AB  - Renal function was prospectively analyzed in 26 evaluable patients, irradiated to
      various doses on their kidneys for neoplastic disease. Glomerular function was
      assessed by 99mTc-DTPA renography, creatinine clearance, and serum beta 2
      microglobulin, whereas tubular function was monitored by 99mTc-DMSA scintigraphy,
      urine beta 2-microglobulin, urine N-acetyl glucosaminidase, and alanine
      aminopeptidase and a urine concentration test. In the patients given the highest
      irradiation dose to the entire left kidney, that is, 40 Gy in 5 1/2 weeks,
      glomerular and tubular functional impairment, as assessed scintigraphically,
      progressed at a rate of 2.0 +/- 1.0% (+/- 1 SD) and 2.0 +/- 0.5% per month,
      respectively, down to 30-40% after 3 to 5 years. The overall glomerular function,
      as assessed by creatinine clearance, decreased by only 20%. In the patients
      irradiated unilaterally on the upper pole to 40 Gy in 4 weeks, glomerular and
      tubular function in the left kidney deteriorated at 0.75 +/- 0.33% and 0.75 +/-
      0.20% per month in the first 2 years, down to 75-80% at 5 years. This smaller
      reduction was due to shielding of a part of the left kidney. No changes were
      observed, thus far, after bilateral whole kidney irradiation to 17-18 Gy in 3 1/2
      weeks. The concentration capacity of the kidney after total volume irradiation
      was not impaired. There was a trend for an increase in diastolic blood pressure
      in 3 out of 5 patients given the high dose irradiation to the entire left kidney
      and in 2 out of 7 patients irradiated on the upper pole of the left kidney. The
      progressive nature of the radiation nephropathy stresses the need for long term
      follow-up to determine more accurately the "tolerance dose" of the human kidney
      for irradiation.

PMID- 1976616
TI  - Inhibition of HIV replication by 19-O-n-pentyldamavaricin Fc in vitro.

PMID- 1976617
TI  - Responses to cimaterol in genetically obese and lean pigs.
AB  - Twenty-four genetically obese and 24 lean barrows were allotted within genotype
      to either a 16% CP corn-soybean meal basal diet, the basal + .69 ppm cimaterol or
      the basal + 1.38 ppm cimaterol. Pigs had ad libitum access to their diets from
      59.3 kg to 104.5 kg body weight. No genotype x cimaterol interactions were
      detected (P greater than .05). Neither genotype nor cimaterol supplementation had
      any effect (P greater than .05) on average daily weight gain or gain-to-feed
      ratio. Compared with lean pigs, obese pigs had higher fasting plasma urea
      nitrogen (BUN), a smaller gastrointestinal tract and a greater dressing
      percentage with a shorter and fatter carcass (P less than .05). Cimaterol
      produced a higher fasting plasma BUN, a greater dressing percentage with a leaner
      carcass and a higher shear force value for loin chops (P less than .05).
      Cimaterol also tended (P less than .10) to increase heart weight. However, no
      difference was observed in these measurements between pigs fed .69 or 1.38 ppm
      cimaterol. In lean pigs fed the basal or .69 ppm cimaterol diet, there was no
      difference (P greater than .05) in the 8 to 24 h postprandial whole-animal heat
      production. Cimaterol effectively decreased fat deposition and increased lean
      accretion both in genetically obese and in lean pigs; there were no differential
      responses to cimaterol in pigs with different propensities to deposit body fat.

PMID- 1976619
TI  - Treatment of psychotic symptoms in Alzheimer's patients.

PMID- 1976618
TI  - Cloning and expression of a Staphylococcus aureus gene encoding a peptidoglycan
      hydrolase activity.
AB  - A gene of Staphylococcus aureus PS47 encoding lytic activity was cloned and
      expressed in Escherichia coli. Deletion analysis of a recombinant plasmid
      carrying a 7.4-kilobase-pair fragment (kbp) of S. aureus DNA suggested that the
      gene was located within a 2.5-kbp EcoRI-XbaI fragment. Analysis of extracts of E.
      coli harboring recombinant plasmids on denaturing polyacrylamide gels containing
      purified cell walls of S. aureus showed a clearing zone by a polypeptide of
      apparent Mr 23,000. The release of dinitrophenylalanine but not reducing groups
      from purified cell walls by a cell extract of recombinant E. coli suggested that
      we had cloned an N-acetylmuramyl-L-alanine amidase.

PMID- 1976620
TI  - Anxiety in the elderly: treatment strategies.
AB  - Anxiety in the elderly is often mixed with depression, and successful
      antidepressant treatment will often also eliminate the anxiety. For specific
      symptoms of generalized anxiety, benzodiazepines are important therapeutic
      agents. Selection of an appropriate benzodiazepine is guided by pharmacokinetic
      properties of individual drugs. Long half-life benzodiazepines usually are not
      preferred for older patients because of cumulative toxicity. Among the short half
      life drugs, high-potency compounds (e.g., lorazepam, alprazolam) may be more
      toxic than low-potency compounds (e.g., oxazepam). Although confirming controlled
      data are lacking, clinical experience suggests that dependence, rebound symptoms,
      and memory impairment may be more intense with lorazepam and alprazolam.
      Clinicians should endeavor to use benzodiazepines for short periods when treating
      the elderly. Long-term use has been reported effective and nonhazardous, but
      subtle and gradual cognitive impairment may occur in other patients over time.
      Buspirone has also been reported as an effective, nontoxic antianxiety compound
      for older patients, but more experience and comparative research data are needed.

PMID- 1976621
TI  - Pharmacologic management of aggression in the elderly.
AB  - Issues related to the epidemiology, nosology, and differential diagnosis of
      organic aggressive disorders in the elderly are discussed. Rating and monitoring
      of aggressive events using the Overt Aggression Scale are reviewed. The
      management of acute aggression with antipsychotic agents and benzodiazepines is
      presented, as well as an approach for using beta-blockers, anticonvulsant agents,
      and serotonin-specific antidepressants and an antianxiety agent for the treatment
      of chronic aggression.

PMID- 1976622
TI  - Insights in the use of trazodone in depressed patients. Proceedings from the VIII
      World Congress of Psychiatry. Athens, Greece, October 12-19, 1989.

PMID- 1976623
TI  - Understanding and treating depression in anxious patients.
AB  - Depression is a common complication of anxiety disorders. Major depressive
      disorder may be the primary diagnosis, the patient having been unaware of
      depressed affect until anxiety became less prominent. Depression may also be a
      comorbid condition, appearing because anxiety lowers the threshold for its
      development or as a result of use of central nervous system depressants or
      intercurrent medical illnesses. Depression may also be a response to psychosocial
      consequences of anxiety or its resolution. In some anxious patients, depression
      is a later stage in the development of a dysregulated stress response. Initial
      treatment of depression involves therapy for organic causative factors and
      psychosocial problems. Medications that may be useful for both depression and
      anxiety include cyclic antidepressants, monoamine oxidase inhibitors, and
      possibly azapirones and benzodiazepines. Combined anxiolytic-antidepressant
      treatment may be necessary for some patients.

PMID- 1976624
TI  - Serotonin partial agonists in the treatment of anxiety and depression.
      Proceedings from the VIII World Congress of Psychiatry. Athens, Greece, October
      12-19, 1989.

PMID- 1976625
TI  - Treatment of social phobias.
AB  - Social phobia, despite a prevalence in the general population of 1.5% denoting a
      common disorder, has been relatively neglected from the viewpoints of
      psychopathology and of treatment. Two subtypes of social phobia have been
      differentiated: specific (characterized by anxiety in one situation, e.g., public
      speaking) and generalized (characterized by anxiety in several social
      situations). The syndrome is frequently complicated by alcohol abuse or
      dependence. Among the treatment targets are symptoms of anxiety, avoidance
      behavior, negative cognitions concerning the reactions of others, and, less
      frequently, social skills deficits. Both pharmacologic and cognitive-behavioral
      treatments have been found effective in this disorder, and it seems likely that
      the two treatments will complement each other. The treatment literature is
      reviewed, and recommendations concerning a state-of-the-art treatment approach to
      both specific and generalized social phobia are made. Potential complications and
      limitations are discussed.

PMID- 1976626
TI  - Characterization of the binding domain of the beta-adrenergic receptor with the
      fluorescent antagonist carazolol. Evidence for a buried ligand binding site.
AB  - The antagonist carazolol has been used as a fluorescent probe for the binding
      site of the beta-adrenergic receptor (beta AR). The fluorescence properties of
      carazolol are dominated by the emission of the carbazole group, with the fine
      structure of the spectrum, but not the quantum yield, sensitive to the
      environment of the probe. The fluorescence emission spectrum of the bound probe
      is consistent with an extremely hydrophobic environment in the binding site of
      the receptor. Binding of carazolol to the purified beta AR increases the
      polarization of the fluorophore. Exposure to collisional quenchers has
      demonstrated the bound carazolol to be completely inaccessible to the solvent.
      Furthermore, the fluorescence of bound carazolol is not quenched by exposure to
      sodium nitrite, a Forster energy acceptor which has an R0 value of 11.7 A with
      carazolol. Thus, physical analysis of the binding site of the beta AR by
      carazolol fluorescence indicates that the antagonist binds to the beta AR in a
      rigid hydrophobic environment which is buried deep within the core of the
      protein.

PMID- 1976627
TI  - A novel transglutaminase-mediated post-translational modification of
      phospholipase A2 dramatically increases its catalytic activity.
AB  - Transglutaminases (TG), which include coagulation Factor XIIIa, are calcium
      dependent ubiquitous enzymes. TGs catalyze the formation of an isopeptide bond by
      cross-linking a specific glutamine and a lysine residue between two proteins or
      within the same protein molecule. Phospholipase A2 (PLA2) is a key enzyme in the
      regulation of prostaglandin and leukotriene biosynthetic pathways, which
      catalyzes the release of free fatty acids from the sn-2 position of membrane
      glycerophospholipids. This enzyme has been suggested to be pathophysiologically
      related to the initiation and propagation of several inflammatory diseases
      including juvenile rheumatoid and rheumatoid arthritis. Here, we describe a novel
      TG-catalyzed post-translational modification of PLA2 which dramatically increases
      the activity of this enzyme. This increase was dependent upon the time of
      preincubation, the concentration of TG and the presence of Ca2+. Size exclusion
      chromatography of TG-treated PLA2 yielded two peaks of PLA2 activity, with
      apparent molecular masses of 26 and 13 kDa, respectively. The 26-kDa species, a
      putative PLA2 dimer, contained epsilon-(gamma-glutamyl)-lysine isopeptide in
      about 1:1 molar ratio to PLA2, suggesting an intramolecular rather than
      intermolecular cross-linking. This hypothesis was confirmed by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis of the 26- and 13-kDa species under
      denaturing conditions. The specific activity of the dimeric peak was 10-fold
      higher with respect to that of the monomeric enzyme. These data suggest that TG
      catalyzed covalent cross-linking of PLA2 is intramolecular and that this may
      promote a noncovalent dimerization and subsequent activation of this enzyme via a
      conformational change. To our knowledge, this is the first demonstration that TG
      mediated post-translational modification of an enzyme (e.g. PLA2) causes a
      striking increase in the catalytic activity of the enzyme.

PMID- 1976628
TI  - Sequence requirements for cytochrome P-450IID1 catalytic activity. A single amino
      acid change (Ile380 Phe) specifically decreases Vmax of the enzyme for bufuralol
      but not debrisoquine hydroxylation.
AB  - A cDNA coding for an allelic variant of rat IID1, designated IID1v, was isolated
      that produced a P-450 having a 10-fold lower catalytic activity toward the
      substrate bufuralol when expressed in COS-1 cells (Matsunaga, E., Zanger, U. M.,
      Hardwick, J. P., Gelboin, H. V., Meyer, U. A., and Gonzalez, F. J. (1989)
      Biochemistry, 28, 7349-7355). IID1 and IID1v cDNA-deduced proteins differed in
      sequence by 4 amino acid residues. IID1 has Val, Phe, Arg, and Leu while IID1v
      has Ile, Leu, Gln, and Phe at amino acid positions 123, 124, 173, and 380,
      respectively. Chimeric cDNAs between IID1 and IID1v were constructed and
      expressed in hepatoma cells using vaccinia virus. A chimera having the Phe
      (IID1v) at amino acid 380, with the remaining 3 variant amino acid residues of
      IID1, was found to have a 17-fold decrease in Vmax and a 2 to 3-fold decrease in
      Km for (+)-bufuralol 1'-hydroxylation when compared to a converse chimera having
      Ile (IID1) in a background of IID1v sequence. Although this enzyme lacked
      significant bufuralol metabolism, it was able to carry out debrisoquine 4
      hydroxylation. In contrast, the chimera having Ile (IID1) at position 380 was
      lacking in debrisoquine 4-hydroxylation. Type I difference spectra analysis
      revealed that both forms could bind debrisoquine with similar spectral
      dissociation constants. These data demonstrate that the single amino acid
      substitution Ile380----Phe differentially decreases the catalytic activity of
      IID1 toward bufuralol but not debrisoquine.

PMID- 1976629
TI  - Structures and chromosomal localizations of two human genes encoding
      synaptobrevins 1 and 2.
AB  - Synaptobrevins 1 and 2 are small integral membrane proteins specific for synaptic
      vesicles in neurons. Two cosmid clones containing the human genes encoding
      synaptobrevins 1 and 2 (gene symbols SYB1 and SYB2, respectively) were isolated
      and characterized. The coding regions of the synaptobrevin genes are highly
      homologous to each other and are interrupted at identical positions by introns of
      different size and sequence. Each gene is organized into five exons whose
      boundaries correspond to those of the protein domains. Exon I contains part of
      the initiator methionine codon whereas exon II encodes the variable and
      immunogenic amino-terminal domain of the synaptobrevins. The third exon comprises
      the highly conserved central domain of the synaptobrevins, exon IV encodes most
      of the transmembrane region, and exon V contains the last residues of the
      transmembrane region and the small intravesicular carboxyl terminus. Comparisons
      of the synaptobrevin sequences in five species from Drosophila with man indicate
      a selective conservation of sequences adjacent to the synaptic vesicle surface,
      suggesting a function at the membrane-cystosol interface. The chromosomal
      localizations of the human and mouse SYB1 and SYB2 genes were determined using
      hybrid cell lines. SYB1 was localized to the short arm of human chromosome 12 and
      to mouse chromosome 6 whereas SYB2 was found on the distal portion of the short
      arm of human chromosome 17 and on mouse chromosome 11. A PstI restriction
      fragment length polymorphism was identified at the SYB2 locus.

PMID- 1976630
TI  - Osmotic control of proU transcription is mediated through direct action of
      potassium glutamate on the transcription complex.
AB  - Osmoregulated transcription from the proU promoter of Escherichia coli has been
      successfully reconstituted from purified components in a simple in vitro system
      consisting of plasmid DNA template, RNA polymerase, and nucleotides in the
      absence of any other protein factor. proU transcription is stimulated by addition
      of high concentrations of potassium glutamate, the ionic compound accumulated in
      vivo during hyperosmotic stress. Transcription from the nonosmoregulated
      promoters beta la, lac, and pepN is inhibited under the same conditions,
      demonstrating the specificity of potassium glutamate as an inducer of proU
      transcription. proU transcription requires a circular DNA template, but stable
      alterations in the degree of supercoiling are unnecessary for this potassium
      glutamate-dependent signaling. These results agree well with previous data
      obtained in an S-30 coupled transcription/translation system and suggest that
      physiological changes in the ionic composition of the intracellular millieu can
      regulate gene expression.

PMID- 1976631
TI  - Formation of high molecular weight dermatan sulfate proteoglycan in bovine aortic
      endothelial cell cultures. Evidence for transglutaminase-catalyzed cross-linking
      to fibronectin.
AB  - Three glucuronate-rich dermatan sulfate proteoglycan (DS-PG) subclasses were
      isolated and previously characterized from bovine aortic endothelial cell
      cultures (Kinsella, M. G., and Wight, T. N. (1988) J. Biol. Chem. 263, 19222
      19231). In the present study, pulse-chase experiments indicate that the DS-PG of
      highest apparent Mr (approximately 1 x 10(6)), denoted previously as HMW-DS, is a
      relatively stable component of the endothelial extracellular matrix and is formed
      at the expense of lower Mr DS-PG species. The formation of HMW-DS is reduced in a
      dose-dependent manner in the presence of dansylcadaverine, an inhibitor of
      transglutaminase-catalyzed protein cross-linking, but not when the activity of
      other cross-linking enzymes such as lysyl oxidase is inhibited. The putative DS
      PG precursor to HMW-DS accumulates during inhibition of cross-linking only when
      lysosomal degradation is also inhibited by ammonium chloride, suggesting that the
      precursor is degraded rapidly in the absence of cross-linking. HMW-DS is
      precipitable from endothelial cell monolayer extracts with antibodies against
      fibronectin, a known transglutaminase substrate. Thus, we conclude that the
      stability of HMW-DS in the subendothelial matrix in culture depends upon the
      cross-linking of a low Mr DS-PG precursor to matrical protein(s), including
      fibronectin, resulting in the formation of a DS-PG subclass of high apparent
      molecular mass.

PMID- 1976632
TI  - A truncation mutation in the avian beta-adrenergic receptor causes agonist
      induced internalization and GTP-sensitive agonist binding characteristic of
      mammalian receptors.
AB  - Recombinant turkey erythrocyte beta-adrenergic receptors expressed in murine L
      cells exhibited characteristic avian subtype selectivity for agonists and
      antagonists. In 10 of the 11 clones studied, no agonist-induced internalization
      of receptor was observed, although agonist-induced uncoupling of receptor and
      adenylyl cyclase occurred rapidly. GTP caused little or no decrease in affinity
      for beta-adrenergic agonists. Such behavior is commonly observed in avian
      erythrocytes. In contrast, one clone was susceptible to agonist-induced receptor
      internalization and down-regulation even though it exhibited characteristic avian
      beta-adrenergic ligand-binding properties. The affinity of this variant receptor
      for agonists was also notably reduced by GTP. Electrophoresis of affinity-labeled
      receptor from this clone indicated an apparent size of about 33 kDa, about 12 kDa
      less than that of the native or recombinant turkey beta-adrenergic receptor.
      Genomic DNA from this cell line that encodes the receptor was cloned and
      partially sequenced. The coding region of the original receptor cDNA was
      interrupted after codon 412 (out of 483) and was followed by 36 base pairs of
      novel sequence prior to the first in-frame stop codon. These results suggest that
      the lack of both hormone-induced internalization and GTP-sensitive, high affinity
      binding of agonists that is characteristic of the beta-adrenergic receptor in
      avian erythrocytes is due to intrinsic properties of the receptor. The
      restoration of these phenomena in a C-terminally truncated mutant receptor
      suggests the importance of the C-terminal domain in determining these processes.

PMID- 1976633
TI  - Identification of somatostatin receptors by covalent labeling with a novel
      photoreactive somatostatin analog.
AB  - We have synthesized two photoreactive derivatives of somatostatin, namely [125I
      Tyr11,azidonitrobenzoyl (ANB)-Lys4]somatostatin and [125I-Tyr11,ANB
      Lys9]somatostatin, and used them to characterize somatostatin receptors
      biochemically in several cell types. Saturation binding experiments carried out
      in the dark demonstrated that [125I-Tyr11,ANB-Lys4]somatostatin bound with high
      affinity (KD = 126 +/- 39 pM) to a single class of binding sites in GH4C1
      pituitary cell membranes. The affinity of this analog was similar to that of the
      unsubstituted peptide [125I-Tyr11]somatostatin (207 +/- 3 pM). In contrast,
      specific binding was not observed with [125I-Tyr11,ANB-Lys9]somatostatin. The
      binding of both [125I-Tyr11,ANB-Lys4]somatostatin and [125I-Tyr11]somatostatin
      was potently inhibited by somatostatin (EC50 = 300 pM) whereas at 100 nM
      unrelated peptides had no effect. Furthermore, both pertussis toxin treatment and
      guanyl-5'yl imidophosphate (Gpp(NH)p) markedly reduced [125I-Tyr11,ANB
      Lys4]somatostatin binding. Thus, [125I-Tyr11,ANB-Lys4]somatostatin binds to G
      protein coupled somatostatin receptors with high affinity. To characterize these
      receptors biochemically, GH4C1 cell membranes were irradiated with ultraviolet
      light following the binding incubation, and the labeled proteins were identified
      by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography.
      A major band of 85 kDa was specifically labeled with [125I-Tyr11,ANB
      Lys4]somatostatin but not with [125I-Tyr11,ANB-Lys9]somatostatin or [125I
      Tyr11]somatostatin. The binding affinity of the 85-kDa protein for [125I
      Tyr11,ANB-Lys4]somatostatin was very high (Kd = 34 pM). Labeling of this protein
      was inhibited competitively by somatostatin (EC50 = 140 +/- 80 pM) but not by
      unrelated peptides. Furthermore, this band was not labeled in pertussis toxin
      treated membranes or in untreated membranes incubated with Gpp(NH)p. Finally,
      [125I-Tyr11,ANB-Lys4]somatostatin specifically labeled bands of 82, 75, and 72
      kDa in membranes prepared from mouse pituitary AtT-20 cells, rat pancreatic
      acinar AR4-2J cells, and HIT hamster islet cells, respectively. Thus, [125I
      Tyr11,ANB-Lys4]somatostatin represents the first photolabile somatostatin analog
      able to bind to receptors with high affinity. Our studies demonstrate that this
      novel peptide covalently labels specific somatostatin receptors in a variety of
      target cell types.

PMID- 1976634
TI  - The in vitro replication of DNA containing the SV40 origin.

PMID- 1976635
TI  - Type II regulatory subunit of protein kinase restores cAMP-dependent
      transcription in a cAMP-unresponsive cell line.
AB  - cAMP-dependent protein kinase appears to play a role in cAMP-induced gene
      expression in mammalian cells. There exist two major types of cAMP-dependent
      protein kinase, type I and type II, which are distinguished by their regulatory
      subunits, RI and RII, respectively. We investigated the role of type I and type
      II protein kinase in the cAMP-induced gene expression by either stable or co
      transfection of RI alpha, RII alpha, or RII beta gene in an expression vector
      together with somatostatin-chloramphenicol acetyltransferase (SS-CAT) fusion gene
      using a cAMP-unresponsive mutant pheochromocytoma cell line (A126-1B2).
      Introduction of the RII beta gene restored the capability of these cells to
      induce the SS-CAT gene expression in response to forskolin stimulus and induced a
      changed morphology which resembled that of wild type. The RII alpha gene also
      induced SS-CAT gene expression but to a lesser degree than that achieved by the
      RII beta gene, whereas the RI alpha gene had no effect. The induction of SS-CAT
      gene expression by the RII beta gene was specifically blocked by the 21-mer RII
      beta antisense oligodeoxynucleotide. These results show for the first time that
      type II but not type I regulatory subunit of cAMP-dependent protein kinase is
      essential for a cAMP-induced gene transcription.

PMID- 1976636
TI  - Transcriptional regulation of glutamine synthetase gene expression by
      dexamethasone in L6 muscle cells.
AB  - Dexamethasone increases glutamine synthetase activity and mRNA abundance in L6
      muscle cells in culture, apparently by a glucocorticoid receptor-mediated
      process. The data in this report reveal that increased glutamine synthetase mRNA
      abundance is attributable at least in part to an enhanced rate of transcription
      of the glutamine synthetase gene. "Nuclear runoff" assays of glutamine synthetase
      gene expression were performed with purified myonuclei from dexamethasone-treated
      or untreated L6 skeletal muscle cells. These assays showed glutamine synthetase
      transcription to be increased approximately 2-fold as early as 1 h after
      incubation of cells with dexamethasone (10(-7) M); there was no increase in the
      rate of transcription of the beta-tubulin gene, which served as a control. The
      increase in glutamine synthetase gene transcription correlates with increased
      glutamine synthetase enzymatic activity after dexamethasone treatment. Studies
      with actinomycin D indicated that the half-life of glutamine synthetase mRNA (7-8
      h) is not altered by dexamethasone. Therefore, the degradation of glutamine
      synthetase mRNA is not affected by dexamethasone, and the increased glutamine
      synthetase mRNA level is attributable to increased transcription. The
      dexamethasone-mediated increase in glutamine synthetase mRNA abundance is
      glucocorticoid receptor-mediated; RU38486 (a glucocorticoid receptor blocker)
      completely blocked the effect of dexamethasone. The dexamethasone-mediated
      increase in glutamine synthetase gene transcription and steady-state mRNA level
      was not blocked by cycloheximide, indicating a direct effect.

PMID- 1976637
TI  - Biogenetic pathways of plasma membrane proteins in Caco-2, a human intestinal
      epithelial cell line.
AB  - We studied the sorting and surface delivery of three apical and three basolateral
      proteins in the polarized epithelial cell line Caco-2, using pulse-chase
      radiolabeling and surface domain-selective biotinylation (Le Bivic, A., F. X.
      Real, and E. Rodriguez-Boulan. 1989. Proc. Natl. Acad. Sci. USA. 86:9313-9317).
      While the basolateral proteins (antigen 525, HLA-I, and transferrin receptor)
      were targeted directly and efficiently to the basolateral membrane, the apical
      markers (sucrase-isomaltase [SI], aminopeptidase N [APN], and alkaline
      phosphatase [ALP]) reached the apical membrane by different routes. The large
      majority (80%) of newly synthesized ALP was directly targeted to the apical
      surface and the missorted basolateral pool was very inefficiently transcytosed.
      SI was more efficiently targeted to the apical membrane (greater than 90%) but,
      in contrast to ALP, the missorted basolateral pool was rapidly transcytosed.
      Surprisingly, a distinct peak of APN was detected on the basolateral domain
      before its accumulation in the apical membrane; this transient basolateral pool
      (at least 60-70% of the enzyme reaching the apical surface, as measured by
      continuous basal addition of antibodies) was efficiently transcytosed. In
      contrast with their transient basolateral expression, apical proteins were more
      stably localized on the apical surface, apparently because of their low endocytic
      capability in this membrane. Thus, compared with two other well-characterized
      epithelial models, MDCK cells and the hepatocyte, Caco-2 cells have an
      intermediate sorting phenotype, with apical proteins using both direct and
      indirect pathways, and basolateral proteins using only direct pathways, during
      biogenesis.

PMID- 1976638
TI  - Epithelial integrin alpha 6 beta 4: complete primary structure of alpha 6 and
      variant forms of beta 4.
AB  - The integrin alpha 6 beta 4 is a heterodimer predominantly expressed by
      epithelia. While no definite receptor function has yet been assigned to it, this
      integrin may mediate adhesive and/or migratory functions of epithelial cells. We
      have determined the complete primary structure of both the alpha 6 and beta 4
      subunits from cDNA clones isolated from pancreatic carcinoma cell line libraries.
      The deduced amino acid sequence of alpha 6 is homologous to other integrin alpha
      chains (18-26% identity). Antibodies to an alpha 6 carboxy terminus peptide
      immunoprecipitated alpha 6 beta 4 complexes from carcinoma cells and alpha 6 beta
      1 complexes from platelets, providing further evidence for the association of
      alpha 6 with more than one beta subunit. The deduced amino acid sequence of beta
      4 predicts an extracellular portion homologous to other integrin beta chains, and
      a unique cytoplasmic domain comprised of greater than 1,000 residues. This agrees
      with the structures of the beta 4 cDNAs from normal epithelial cells (Suzuki, S.,
      and Y. Naitoh. 1990. EMBO [Eur. Mol. Biol. Organ.] J. 9:757-763; Hogervost, F.,
      I. Kuikman, A. E. G. Kr. von dem Borne, and A. Sonnenberg. 1990. EMBO [Eur. Mol.
      Biol. Organ.] J. 9:765-770). Compared to these structures, however, the beta 4
      cDNAs that we have cloned from carcinoma cells contain extra sequences. One of
      these is located in the 5'-untranslated region, and may encode regulatory
      sequences. Another specifies a segment of 70 amino acids in the cytoplasmic tail.
      Amplification by reverse transcription-polymerase chain reaction of mRNA
      indicated that multiple forms of beta 4 may exist, possibly due to cell-type
      specific alternative splicing. The unique structure of beta 4 suggests its
      involvement in novel cytoskeletal interactions. Consistent with this possibility,
      alpha 6 beta 4 is mostly concentrated on the basal surface of epithelial cells,
      but does not colocalize with components of adhesion plaques.

PMID- 1976640
TI  - Butyrate blocks the accumulation of CDC2 mRNA in late G1 phase but inhibits both
      the early and late G1 progression in chemically transformed mouse fibroblasts BP
      A31.
AB  - Sodium butyrate (6 mM) blocks the resumption of the cell division cycle in serum
      deprived chemically transformed Balb/c-3T3 mouse fibroblasts (BP-A31). The
      inhibition of G1 progression by sodium butyrate is not restricted to a specific
      mitogenic signaling pathway and is equally effective when tetradecanoyl phorbol
      acetate (TPA), insulin, or fetal calf serum (FCS) is used as inducer. The
      inhibitor acts in early as well as late G1 phase as indicated by experiments in
      which inhibitor was added and withdrawn at different times after restimulation of
      quiescent cells by FCS. At the gene expression level, sodium butyrate does not
      affect the inducibility of early cell cycle-related genes (c-myc, c-jun) while
      blocking the induction of cdc 2 mRNA, a late G1 marker. We conclude that sodium
      butyrate does not interfere with the growth factor signaling pathways regulating
      the (early) cell cycle-related gene expression. However, the presence of sodium
      butyrate early in G1 phase inhibits the cascade of events leading eventually to
      the expression of late G1-characteristic genes such as cdc2. The antimitogenic
      activity of sodium butyrate may be related to its interference with an (unknown)
      process involved in the "mitogenic" cascade.

PMID- 1976641
TI  - Amine-induced responses of pial and penetrating cerebral arteries: evidence for
      heterogeneous responses.
AB  - Middle cerebral arteries (MCAs) of rabbits were compared with two types of small
      branches (less than 100-microns outer diameter), penetrating arteries (PAs) and
      surface arteries (SAs), by determining their mechanical reactivity to several
      amines and standard contractile agents. Two techniques were employed: (a)
      measurement of isometric tension of 1-mm rings (MCA, PA, or SA); (b) measurement
      of perfusion pressure of segments consisting of essentially MCA or essentially
      PA. Both techniques revealed similar reactivity of the different types of vessel
      to acetylcholine, i.e., relaxations to a maximum of 52-78%, and similar strong
      contractile responses to histamine, although the MCA was more sensitive. Under H1
      blockade, histamine dilated the PA (both techniques) and the MCA (perfusion
      technique), but not the SA. Relatively weak contractile responses to serotonin
      were observed in the MCA (both techniques) and the PA (perfusion technique), but
      not the SA (isometric tension only); no dilative responses could be elicited.
      Responses to noradrenaline varied with the vessel considered: The MCA contracted
      only, whereas the PA weakly contracted or relaxed at basal tone, and many
      preparations relaxed after precontraction with uridine triphosphate; the SA did
      not react. Relaxation of precontracted PA by noradrenaline occurred at relatively
      low concentrations and was antagonized by propranolol at 3 x 10(-7) or 3 x 10(-6)
      M. These results reveal very significant differences in the segmental reactivity
      to amines and suggest that noradrenaline released from sympathetic fibers might
      have opposing actions in the major pial arteries and the smaller penetrating
      branches.

PMID- 1976639
TI  - Functional reconstitutional of the human epidermal growth factor receptor system
      in Xenopus oocytes.
AB  - We have expressed the human EGF receptor (hEGF-R) in Xenopus oocytes by injecting
      mRNA synthesized in vitro using SP6 vectors containing receptor cDNAs. Each
      oocyte could express over 1 x 10(10) receptors of a single affinity class and
      these were able to bind and rapidly internalize EGF. Occupancy resulted in
      receptor tyrosine autophosphorylation, downregulation, and release of
      intracellular calcium. Occupied receptors also rapidly induced meiotic maturation
      in stage VI oocytes. Receptors lacking tyrosine kinase activity bound EGF
      normally, but did not downregulate or induce any biological responses. The rate
      of oocyte maturation was proportional to hEGF-R occupancy and was significantly
      faster than progesterone-induced maturation at nanomolar EGF concentrations.
      Mutant hEGF-R truncated at residue 973 displayed identical phenotypes in both
      mammalian cells and oocytes in that they were defective in their ability to
      release intracellular calcium, undergo ligand induced internalization and
      receptor downregulation. However, these receptors were fully capable of inducing
      oocyte maturation. The remarkable retention of specific biological activities of
      different hEGF-R in the context of oocytes suggests that this receptor system
      interacts with generally available cellular components that have been conserved
      during evolution. In addition, it suggests that cell surface tyrosine kinase
      activity may play an important role in regulating resumption of the cell cycle.

PMID- 1976642
TI  - Protection against ischemia-induced neuronal damage by the alpha 2-adrenoceptor
      antagonist idazoxan: influence of time of administration and possible mechanisms
      of action.
AB  - The protective effect of the alpha 2-receptor antagonist idazoxan against
      neuronal damage in the neocortex and in the hippocampal CA1 region was studied in
      rats exposed to 10 min of incomplete forebrain ischemia. When administered i.v.
      immediately after ischemia (0.1 mg/kg) and subsequently for 6 h (10
      micrograms/kg/min), idazoxan significantly reduced neuronal damage in the
      hippocampus (from 84 to 26%) and in the vulnerable parts of the neocortex (from
      15 to 1%). The bolus dose alone provided no significant protection. When idazoxan
      administration was delayed for 30 min, no significant protection was noticed in
      the neocortex, and the effect in the hippocampus was ambiguous. A transient
      elevation of plasma corticosterone levels was induced during ischemia. Idazoxan
      administration for 2 h did not affect postischemic changes in corticosterone
      levels compared with saline infusion. Idazoxan (10(-7)-10(-4) M) did not
      influence the in vitro binding to glutamate receptors in brain slices. Thus, the
      protective effect of idazoxan cannot be explained by suppression of the plasma
      corticosteroid levels or via an antagonistic effect on glutamate receptors.
      Idazoxan apparently protects neurons when given during the first hours of
      postischemic reperfusion, while histopathological necrosis of neurons becomes
      visible 48-72 h after ischemia. Detrimental processes causing delayed neuronal
      death occur in the early postischemic phase and can be influenced by adrenoceptor
      ligands. Idazoxan may protect by several mechanisms but probably exerts its
      protective postischemic effect mainly through an increased noradrenergic neuronal
      activity and an elevation of extracellular noradrenaline (NA) levels in the
      brain. The favorable effects of NA may either be due to inhibition of excitotoxic
      neurotransmission or activation of survival-promoting and trophic processes.

PMID- 1976643
TI  - Risk factors and long-term diabetic complications. Proceedings of the Diabetic
      Complications Symposium I. Copenhagen, October 6-7, 1989.

PMID- 1976645
TI  - The use of cefoxitin in anaerobic and aerobic infections. Based on the
      proceedings of a symposium. June 2 and 3, 1989, Carlsbad, California.

PMID- 1976644
TI  - Insulin sensitivity and blood lipids during antihypertensive treatment with
      special reference to ACE inhibition.
AB  - NIDDM and hypertension are both characterized by insulin resistance and/or
      hyperinsulinemia. In IDDM, factors associated with nephropathy produce
      hypertension. To avoid exacerbation of the metabolic condition, and to prevent
      further deterioration in glycemic control, treatment of hypertension in the
      diabetic patient should include the administration of medication with the fewest
      adverse effects on glucose homeostasis. If diuretics are to be used, it appears
      that loop diuretics may be preferable to the thiazides or potassium-sparing
      compounds. Among the remaining classes of antihypertensive drugs, ACE inhibitors
      may be the agents of choice because of their potential positive effects on
      insulin sensitivity and renal function, and their lack of severe adverse side
      effects.

PMID- 1976646
TI  - Determination of metazosin in biological fluids by reversed-phase high
      performance liquid chromatography with fluorescence detection.

PMID- 1976647
TI  - High-performance liquid chromatographic system for the separation of dynorphin A
      (1-17) fragments and its application in enzymolysis studies with rat nerve
      terminal membranes.
AB  - A high-performance liquid chromatographic method capable of separating a large
      number of C- and N-terminal degradation fragments of dynorphin A (1-17) (dyn 1
      17) in 1 h has been developed. The system has been applied to study the
      metabolism profiles of various dyn 1-17-derived peptides following in vitro
      incubation with rat striatum and spinal cord nerve terminal membranes. In
      addition to the removal of the N-terminal amino acid Tyr, major sites of cleavage
      between the following amino acids could be established: Leu5-Arg6 in dyn 1-7
      (formation of dyn 1-5); Arg6-Arg7 and Leu5-Arg6 in dyn 1-8 (formation of dyn 1-6
      and dyn 1-5, respectively); Arg7-Ile8 in dyn 1-9 (formation of dyn 1-7) and Arg9
      Pro10 in dyn 1-10 (formation of dyn 1-9). Studies with inhibitors of the enzymes
      involved show that dyn 1-5 is formed directly from dyn 1-8 via an endopeptidase
      insensitive to the angiotensin-converting enzyme inhibitor MK 422 acting on the
      scissile Leu5-Arg6 bond in dyn 1-8. The method circumvents the use of [3H]Tyr
      labelled dynorphins, which have the inherent drawback that fragments lacking the
      N-terminal Tyr cannot be detected. Owing to the high resolution, also for the
      larger dynorphins dyn 1-14, dyn 1-15 and dyn 1-16, the chromatographic system
      should prove especially useful in the elucidation of the enzymolysis pattern of
      dyn 1-17. Furthermore, the method offers a way to evaluate simultaneously the
      selectivity of new enzyme inhibitors for several cleavage sites in the same
      assay.

PMID- 1976648
TI  - High-performance liquid chromatographic determination of four kinds of biotin
      containing carboxylase.
AB  - A convenient and reliable reversed-phase liquid chromatographic assay for four
      kinds of carboxylase, i.e. pyruvate carboxylase, acetyl-coenzyme A carboxylase,
      propionyl-coenzyme A carboxylase, and 3-methylcrotonyl-coenzyme A carboxylase,
      was developed. These are all biotin enzymes, which contain covalently bound
      biotin as a co-factor (co-enzyme). This chromatographic method, which is free
      from interferences, gives a stoichiometric and precise assay for these enzymes.
      It is non-radioisotopic, which makes it suitable for clinical laboratories. The
      assay time required for one sample is ca. 30 min. The method was satisfactorily
      applied to guinea-pig kidney homogenates after a simple pretreatment with acid.

PMID- 1976650
TI  - Effects of long-term sensory vs. sympathetic denervation on the distribution of
      calcitonin gene-related peptide and tyrosine hydroxylase immunoreactivities in
      the rat lung.
AB  - In this study the effect of long-term selective sensory vs. sympathetic
      denervation was examined in the rat lung. Immunoreactivities for calcitonin gene
      related peptide (CGRP) on the one hand and tyrosine hydroxylase (TH) on the
      other, were used as indexes to assess the changes in the two nerve systems.
      Following long-term chemosympathectomy a marked increase of CGRP-immunoreactive
      nerve fibers was seen in the sections, while TH-immunoreactive nerve fibers
      appeared depleted. Inversely, long-term sensory denervation resulted in an
      increase of TH-immunoreactive nerve fibers with a sharp decrease of CGRP
      immunostained fibers. These results suggest a peripheral interaction between
      these innervation systems in the lung, the mechanism of which has still to be
      elucidated.

PMID- 1976651
TI  - High affinity specific binding of vasoactive intestinal peptide to human
      circulating T cells, B cells and large granular lymphocytes.
AB  - We studied the specific binding of vasoactive intestinal peptide (VIP) to
      circulating lymphocytes (PBL) of normal subjects using the interaction of 125I
      VIP with different PBL fractions and flow cytometry to detect the binding of VIP
      coated polystyrene spheres to individual cells of the fractions. Enhanced binding
      of 125I-VIP was found with T-enriched compared to unseparated or T-depleted PBL
      preparations. Both CD4 and CD8 T cell-enriched suspensions showed high binding
      capacity, but the affinity of CD4-enriched preparation for VIP was higher. VIP
      coated spheres also bound to individual T cells of PBL, but only a minority of
      CD4 T cells (32%) and CD8 T cells (23%) bound the spheres. 125I-VIP also
      specifically bound to fractions enriched for large granular lymphocytes (LGL) and
      B cells. A consistent proportion of CD16 marker-positive LGL bound VIP-coated
      spheres (24%, and approximately 15% of B cells also showed this ability. Thus
      there is marked heterogeneity in the ability of different phenotypes of normal
      human circulating lymphocytes to recognize this neuropeptide.

PMID- 1976649
TI  - Immunodeficient mice xenografted with human lymphoid cells: new models for in
      vivo studies of human immunobiology and infectious diseases.
AB  - This review article deals with the transfer of human lymphoid or hematopoietic
      tissues to severely immunodeficient mice to create new small animal models for
      the study of human biology and disease. The degree of functional reconstitution
      in the three current models is discussed. SCID mice with human grafts have been
      infected with human immunodeficiency virus (HIV) to generate a small animal model
      for AIDS research. Epstein-Barr virus (EBV)-related lymphoproliferative disorders
      can also be modeled by the transfer of adult peripheral blood mononuclear cells
      to SCID mice.

PMID- 1976652
TI  - Expression of alpha-adrenoceptors in a human transformed lymphoblastoid cell
      line.
AB  - The presence of alpha-adrenergic receptors (absent in normal lymphocytes) has
      been demonstrated in transformed human lymphocytes of the Raji cell line. Binding
      properties of beta-adrenergic receptors were similar to those reported for normal
      lymphocytes. A single population of alpha 2-adrenergic receptors was
      characterized in intact Raji lymphoblasts by binding and saturation assays with
      the alpha 2-adrenergic antagonist yohimbine. Competition curves with
      [3H]yohimbine indicate the presence of typical alpha 2-adrenoceptors. Reaction of
      Raji with the alpha 2-adrenergic agonist clonidine (10(-6) M) stimulated their
      growth rate. In contrast, the alpha 1-adrenergic agonist methoxamine (10(-6) M)
      had no effect. Previous work indicates that Raji can actively produce
      thromboxanes (TX) and that these decreased atrium contractility. In agreement
      with these results and with the binding studies, it is now shown that clonidine
      stimulation enhanced the negative inotropic effects of Raji on isolated rat
      atria. This reaction was prevented by incubation of Raji with yohimbine (10(-6)
      M) but not with the alpha 1-adrenergic antagonist prazosin (10(-6) M) or the beta
      adrenergic antagonist propranolol (10(-7) M). The biologic effect of Raji on rat
      atria was probably due to production of cyclooxygenase metabolites of arachidonic
      acid, because it was blocked by preincubation of the cells with the
      cyclooxygenase inhibitors indomethacin (10(-6) M) and aspirin (10(-4) M) or the
      thromboxane synthetase inhibitors nictindol (10(-5) M) and imidazole (10(-4)
      M).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1976653
TI  - Relationship between the content of lysyl oxidase-dependent cross-links in skin
      collagen, nonenzymatic glycosylation, and long-term complications in type I
      diabetes mellitus.
AB  - Many abnormalities in collagen have been reported in insulin-dependent diabetes
      mellitus, some or all of which have been attributed to increased cross-linking.
      Although recent work has focused on the role of glucose-derived collagen cross
      links in the pathogenesis of diabetic complications, relatively few studies have
      investigated the role of lysyl oxidase-dependent (LOX) cross-links. In the
      present study, LOX cross-links and nonenzymatic glycosylation were quantified in
      skin collagen from diabetic subjects. There was an increase in the difunctional
      cross-link dihydroxylysinonorleucine (DHLNL) as well as in one of its
      trifunctional maturation products, hydroxypyridinium. All other LOX crosslinks
      were normal. Nonenzymatic glycosylation was increased in diabetic skin collagen,
      and this increase was correlated with increases in DHLNL (P less than 0.001). The
      biochemical results were examined for correlations with clinical data from the
      same subjects. Increases in DHLNL content were associated with duration of
      diabetes (P less than 0.003), glycohemoglobin levels (P less than 0.001), hand
      contractures (P less than 0.05), skin changes (P less than 0.005), and
      microalbuminuria (P less than 0.01). In nondiabetic subjects age was not
      correlated with collagen cross-link content with the exception that his-HLNL
      increased with age (r = 0.79, P less than 0.02). In diabetic subjects, PA levels
      decreased with age (r = 0.51, P less than 0.02). With increased duration of
      diabetes, DHLNL content was increased (r = 0.55, P less than 0.003) and OHP was
      increased (r = 0.59, P less than 0.01), whereas PA levels were decreased (r = 
      0.48, P less than 0.04). Nonenzymatic glycosylation of collagen was also
      increased with increased duration of diabetes (hex-lys, r = 0.47, P less than
      0.02; hex-hyl, r = 0.39, P less than 0.05). We conclude that: (a) lysyl oxidase
      dependent cross-linking is increased in skin collagen in diabetes and (b) that
      these changes in skin collagen are correlated with duration of diabetes, glycemic
      control, and long-term complications.

PMID- 1976655
TI  - An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene
      accounting for half the variance of serum enzyme levels.
AB  - A polymorphism consisting of the presence or absence of a 250-bp DNA fragment was
      detected within the angiotensin I-converting enzyme gene (ACE) using the
      endothelial ACE cDNA probe. This polymorphism was used as a marker genotype in a
      study involving 80 healthy subjects, whose serum ACE levels were concomitantly
      measured. Allele frequencies were 0.6 for the shorter allele and 0.4 for the
      longer allele. A marked difference in serum ACE levels was observed between
      subjects in each of the three ACE genotype classes. Serum immunoreactive ACE
      concentrations were, respectively, 299.3 +/- 49, 392.6 +/- 66.8, and 494.1 +/-
      88.3 micrograms/liter, for homozygotes with the longer allele (n = 14), and
      heterozygotes (n = 37) and homozygotes (n = 29) with the shorter allele. The
      insertion/deletion polymorphism accounted for 47% of the total phenotypic
      variance of serum ACE, showing that the ACE gene locus is the major locus that
      determines serum ACE concentration. Concomitant determination of the ACE genotype
      will improve discrimination between normal and abnormal serum ACE values by
      allowing comparison with a more appropriate reference interval.

PMID- 1976654
TI  - Biogenesis of intestinal lactase-phlorizin hydrolase in adults with lactose
      intolerance. Evidence for reduced biosynthesis and slowed-down maturation in
      enterocytes.
AB  - Enzymatic activity, biosynthesis, and maturation of lactasephlorizin hydrolase
      (LPH) were investigated in adult volunteers with suspected lactose intolerance.
      Mean LPH activity in jejunal biopsy homogenates of these individuals was 31%
      compared to LPH-persistent individuals, and was accompanied by a reduced level of
      LPH-protein. Mean sucrase activity in individuals with low LPH was increased to
      162% and was accompanied by an increase in sucrase-isomaltase (SI)-protein.
      Biosynthesis of LPH, SI, and aminopeptidase N (APN) was studied in organ culture
      of small intestinal biopsy specimens. In individuals with LPH restriction, the
      rate of synthesis of LPH was drastically decreased, reaching just 6% of the LPH
      persistent group after 20 h of culture, while the rate of synthesis of SI
      appeared to be increased. In addition, maturation of pro-LPH to mature LPH
      occurred at a slower rate in LPH-restricted tissue. Immunoelectron microscopy
      revealed an accumulation of immunoreactive LPH in the Golgi region of enterocytes
      from LPH-restricted individuals and reduced labeling of microvillus membranes.
      Therefore, lactose intolerance in adults is mainly due to a decreased
      biosynthesis of LPH, either at the transcriptional or translational level. In
      addition, intracellular transport and maturation is retarded in some of the LPH
      restricted individuals, and this leads to an accumulation of newly synthesized
      LPH in the Golgi and a failure of LPH to reach the microvillus membrane.

PMID- 1976656
TI  - "Pulseless" transcranial Doppler findings in Takayasu's arteritis.

PMID- 1976657
TI  - Catecholaminergic innervation of the hippocampus in the cynomolgus monkey.
AB  - We studied the immunocytochemical distribution of catecholaminergic fibers in the
      hippocampal formation from two cynomolgus monkeys by using phenylethanolamine-N
      methyltransferase, dopamine-beta-hydroxylase, and tyrosine-hydroxylase
      antibodies. There were no phenylethanolamine-N-methyltransferase immunoreactive
      fibers suggesting the lack of epinephrine containing fibers. In order to compare
      the distributions of tyrosine-hydroxylase and dopamine-beta-hydroxylase
      immunoreactive fibers, we counted fibers in four hippocampal regions, the dentate
      gyrus, CA3, CA1, and the subiculum at three different rostrocaudal levels. The
      distributions of dopamine-beta-hydroxylase and tyrosine-hydroxylase
      immunoreactive fibers were overlapping but clearly different, suggesting that the
      hippocampus receives both noradrenergic and dopaminergic inputs in primates.
      Dopamine-beta-hydroxylase-immunoreactive fibers were present in moderate density
      and roughly evenly distributed throughout the hippocampus. Tyrosine-hydroxylase
      immunoreactive fibers were found in high density in the dentate gyrus, in the
      stratum lacunosum-moleculare, and in the molecular layer of the subiculum. There
      were only minor side-side and rostrocaudal differences in the distribution of
      tyrosine-hydroxylase and dopamine-beta-hydroxylase immunoreactive fibers. The
      identification of a putative dopaminergic projection to primate hippocampus,
      which is more dense and widely distributed than in the rodent, parallels similar
      increases in dopaminergic projections reported for primate cerebral neocortex.

PMID- 1976658
TI  - Efficacy and persistence of Bacillus sphaericus, Bacillus thuringiensis var.
      israelensis, and methoprene against Culiseta incidens (Diptera: Culicidae) in
      tires.
AB  - The efficacy and persistence of Bacillus sphaericus (2362) was compared at three
      dosage rates in tires that continually contained cadavers of Culiseta incidens
      (Thomson) versus tires with all dead larvae removed. At treatment rates of 3.75
      and 7.5 ppm, the continual presence of cadavers in the tire water resulted in
      higher mortality rates. At the 15 ppm treatment rate, mortality rates were
      similar in tires with or without cadavers. Mortality rates increased in all tires
      4-6 wk after treatment, suggesting an amplification of the pathogen. The
      mortality rate did not exceed 90% for greater than 2 wk in any of the tires. At a
      second site, the efficacy of B. sphaericus, Bacillus thuringiensis var.
      israelensis, and methoprene was evaluated against C. incidens in tires exposed to
      full sunlight versus shaded tires. In shaded tires inoculated with B. sphaericus
      (15 ppm) and B. thuringiensis var. israelensis (15 ppm), mortality exceeded 90%
      for 5 and 2 wk, and 50% for 10 and 4 wk, for the two bacteria, respectively.
      Larvae were adequately controlled (greater than 75% mortality) in the sunny tires
      for approximately 1 wk. The insect growth regulator, methoprene (applied at 2.5
      ppm), inhibited the emergence of approximately 90% of the larvae present at the
      time of treatment, but not of larvae subsequently introduced into either the
      sunny or shaded tires.

PMID- 1976659
TI  - Changes in platelet 5-hydroxytryptamine uptake in mania.
AB  - [3H]5-Hydroxytryptamine (5HT) platelet uptake was examined in a small group of
      hospitalised drug-free manic patients and in a larger group of drug-treated manic
      and schizophrenic patients compared to controls. 5HT platelet uptake was
      significantly higher in the manic group at the beginning of the illness episode
      than in either schizophrenics or controls. No difference was found in the uptake
      rates between the schizophrenics and controls. At discharge, manic patients had
      5HT uptake values similar to control subjects. Manic patients with no previous
      history of either mania or depression had highly significant increases in 5HT
      platelet uptake compared to either schizophrenics, controls or manic patients
      with a previous history of manic-depression. No correlation was found between the
      initial increased 5HT uptake rate in the manic patient and the severity or
      duration of the illness episode, the length of hospitalisation or the gender of
      the patient.

PMID- 1976660
TI  - Evaluating a behavioral method to manage dental fear: a 2-year study of dental
      practices.
AB  - Eleven private general practices and a university clinic formed a network to
      treat dental fear. The practices located in four states learned a method of
      treating dental fear using dental staff members and audiovisual materials. This
      study is an evaluation of the network's effectiveness. In 15 months, 111 patients
      were treated by the network. The dentists reported providing substantial dental
      treatment to 77% (n = 86) of the patients. The study showed that private general
      practices can effectively treat strong dental fear.

PMID- 1976661
TI  - Tolerance to intravenous nitroglycerin in patients with congestive heart failure:
      role of increased intravascular volume, neurohumoral activation and lack of
      prevention with N-acetylcysteine.
AB  - To better understand the mechanism of nitrate tolerance in patients with
      congestive heart failure, 13 patients received a 24 h infusion of nitroglycerin
      (1.5 micrograms/kg body weight per min) with or without N-acetylcysteine (225
      mg/kg per 24 h). The infusions were separated by a 24 h nitrate-free interval. By
      the end of the nitroglycerin infusion, mean arterial pressure had returned to
      baseline values and there was a significant increase in ventricular filling
      pressures and systemic vascular resistance compared with values after 1 h of
      treatment. The simultaneous infusion of N-acetylcysteine had no effect on these
      changes. Although a strict fluid restriction of 1.5 liters/day was maintained for
      1 week before and throughout the study, after 24 h of nitroglycerin infusion
      there was a significant and similar degree of hemodilution whether nitroglycerin
      was infused alone (9.1 +/- 4.3%) or with N-acetylcysteine (8.7 +/- 4.1%). This
      hemodilution corresponded to an increase in intravascular volume of 745 +/- 382
      ml, most of which occurred during the 1st h. Plasma renin activity increased and
      plasma atrial natriuretic peptide decreased during the infusion. The results of
      this study suggest that nitrate tolerance is multifactorial. In addition to the
      previously described pharmacologic tolerance to the effect of nitroglycerin on
      vascular smooth muscle, a capillary fluid shift from the extravascular to
      intravascular space appears to be involved, especially during the 1st h of the
      infusion. A third mechanism, reflex neurohumoral activation, also seems to
      contribute to the genesis of nitroglycerin tolerance.

PMID- 1976663
TI  - Papers presented at a conference on Nutritional and Functional Qualities of
      Microparticulated Protein. Berkeley, California, November 27, 1989. Proceedings.

PMID- 1976662
TI  - What causes tolerance to nitroglycerin? The 100 year old mystery continues.

PMID- 1976664
TI  - In vivo effects of cetirizine on cutaneous reactivity and eosinophil migration
      induced by platelet-activating factor (PAF-acether) in man.
AB  - The aim of the study was to determine the effect of cetirizine, a new potent H1
      antihistamine, on acute cutaneous inflammatory response and eosinophil
      accumulation induced in vivo by platelet-activating-factor (PAF-acether) and
      allergen. In a double-blind, crossover study, seven subjects allergic to grass
      pollen and three nonallergic control subjects received orally either cetirizine,
      20 mg/day, or placebo for 4 days. On day 4, the subjects were skin tested with
      grass pollen and PAF-acether (400 and 40 ng per site). After the challenge, an
      evaluation of time-course cutaneous eosinophil infiltrations by a skin window
      technique was performed. Cetirizine pretreatment reduced skin wheal and erythema
      elicited by allergen and PAF, 400 and 40 ng, by 74.6% (p less than 0.001), 53.9%
      (p less than 0.001), and 47% (p less than 0.01), respectively. Skin reactivity
      induced by PAF-acether was also significantly reduced by cetirizine in
      nonallergic subjects. Cetirizine reduced at hour 24 eosinophil infiltrations
      induced by allergen and PAF, 400 and 40 ng, by 63% (p less than 0.001), 58.5% (p
      less than 0.001), and 57.8% (p less than 0.01), respectively. This inhibitory
      effect of cetirizine on allergen and PAF-induced eosinophil infiltration was
      already effective 2 hours after the challenge. PAF induced a nonsignificant
      eosinophil influx in all nonallergic subjects. In conclusion, cetirizine
      inhibited both the immediate cutaneous response and the eosinophil influx induced
      by allergen and by a potent eosinophil chemotactic factor, such as PAF-acether.
      Therefore, cetirizine, besides its anti-H1 effect, has the potential to modulate
      the allergic inflammatory response.

PMID- 1976665
TI  - The effects of an H1-receptor antagonist, terfenadine, on histamine-induced
      microcirculatory changes and vasopermeability in nasal mucosa.
AB  - We used a nonsedating, selective histamine H1-receptor antagonist, terfenadine,
      to investigate the effects of antihistamines on the microcirculatory changes and
      vascular permeability induced by topical histamine provocation challenge. We
      assessed the former by the laser-Doppler measurement of blood flow, volume, and
      red blood cell speed, and the latter by analysis of albumin/total protein ratios
      in nasal lavages. Terfenadine reduced the mean symptom score and permeability
      changes (p less than 0.05) induced by histamine in a dose-related manner.
      Terfenadine had no effect on blood flow or other microcirculatory parameters. We
      propose that vascular effects of histamine in the nasal mucosa are not mediated
      uniquely through the H1 receptor.

PMID- 1976666
TI  - Risk of systemic reactions in patients taking beta-blocker drugs receiving
      allergen immunotherapy injections.
AB  - To learn whether patients taking beta-blocker (BB) drugs were at increased risk
      of having systemic reactions (SRs) from allergen immunotherapy, we prospectively
      studied 56,105 injection visits in 3178 patients during a 1-year interval. A
      total of 166 SRs occurred in 144 patients (4.5% of all patients) or 3.0 SRs
      occurred per 1000 injection visits. Sixty-eight patients were taking BB drugs
      throughout the year, and only one patient had an SR. By chance, 3.08 patients
      were expected to have had SRs. We conclude that BB drugs did not increase the
      frequency of SRs in the patients studied who were receiving immunotherapy (p
      greater than 0.95). Patients taking BB drugs may still be at increased risk,
      however, from more severe SRs or their SRs may be more refractory to therapy.

PMID- 1976667
TI  - Opioid agonists, prostaglandin E1 and clonidine modulate non-adrenergic, non
      cholinergic transmission in the mammalian heart.

PMID- 1976668
TI  - Cerebral cortical vasodilatation in response to stimulation of cholinergic fibres
      originating in the nucleus basalis of Meynert.
AB  - The recent works in our laboratory, concerning neural regulation of the cerebral
      cortical blood flow by intracranial cholinergic nerve fibres originating in the
      magnocellular nucleus of the basal forebrain (nucleus basalis of Meynert), are
      introduced. Unilateral focal stimulation of the nucleus basalis of Meynert,
      either electrical or chemical, increased blood flow in the ipsilateral cerebral
      cortex in rats anesthetized with urethane or halothane. These vasodilator
      responses were almost completely abolished by intravenous administrations of
      muscarinic and nicotinic cholinergic blocking agents (atropine 0.5 mg/kg and
      mecamylamine 2 mg/kg). Electrical or chemical stimulation of the nucleus basalis
      of Meynert increased acetylcholine release in the ipsilateral cerebral cortex.
      These data suggest that intracranial cholinergic fibres originating in the
      nucleus basalis of Meynert and projecting to the cerebral cortex contribute to
      the vasodilatation of the cortical blood vessels.

PMID- 1976669
TI  - Pre-junctional regulation of sympathetic neurotransmission in the mouse vas
      deferens: assessment of agonist and antagonist potencies.
AB  - Dopaminergic agonists and antagonists were tested on the field-stimulated mouse
      vas deferens. Both LY 171555 and SK & F 38393, relatively selective DA2 and DA1
      receptor agonists, respectively, produced concentration-dependent inhibition of
      the field stimulation-induced contractions, without modifying the baseline tone
      nor the contractile responses to the exogenous noradrenaline. Both LY 171555 and
      SK & F 38393 concentration-response curves were shifted rightward in a parallel
      manner by sulpiride (relatively specific DA2 antagonist) and SCH 23390
      (relatively specific DA1 antagonist), respectively. The results are suggestive of
      the existence of pre-junctional dopamine receptors involved in the regulation of
      sympathetic neurotransmission in rodent vasa.

PMID- 1976670
TI  - The role of ANF in functional properties of the central pathways of
      cardiovascular reflexes.

PMID- 1976672
TI  - The Fifth Consensus Conference on Testing for Human Retroviruses. Kansas City,
      Missouri, March 6-8, 1990. Proceedings.

PMID- 1976671
TI  - Bicarbonate secretion in isolated guinea pig antrum.
AB  - HCO3- secretion was investigated in isolated guinea pig antral mucosa mounted in
      Ussing chambers. The rate of HCO3- secretion was measured by a pH-stat system.
      The antral mucosa spontaneously secreted HCO3- at a rate of about 0.5 microEq cm
      2 h-1. Bethanechol (100 microM) or 8-bromoadenosine 3':5'-cyclic monophosphate (8
      Br-cAMP, 1 mM) induced a significant increase in HCO3- secretion. Prostaglandin
      E2 (1 microM) also produced an increase in HCO3- secretion, although it was less
      effective than either bethanechol or 8-Br-cAMP. Histamine (100 microM) did not
      affect HCO3- secretion. This preparation may be suited to the study of the
      precise mechanisms by which neurohumoral factors regulate gastric HCO3-
      secretion.

PMID- 1976673
TI  - Vasodilator therapy for angina pectoris: the intersection of homeopathy and
      scientific medicine.

PMID- 1976674
TI  - Immunohistochemical localization of P-glycoprotein in adult human ovary and
      female genital tract of patients with benign gynecological conditions.
AB  - The multidrug-resistance gene, MDR1, encodes a plasma membrane glycoprotein
      termed P-glycoprotein, which mediates active cellular efflux of certain cytotoxic
      agents. Two mouse monoclonal antibodies (MAb), C219 and JSB-1, were used to
      identify P-glycoprotein in frozen tissue from the female genital tract of 14
      women with benign gynecological conditions; multiple samples from several sites
      in the genital tract were available from seven patients. P-glycoprotein was
      detected in the ovarian surface epithelium in four of 14 cases, in the Fallopian
      tube in three of five cases, in occasional epithelial cells of the endometrial
      glands in two of five cases, in some endocervical glandular epithelium in three
      of five cases, in ectocervical squamous epithelium in one of the two cases, and
      in luteinized cells of the eight cases in which a corpus luteum was present in
      the specimen. Positive staining with these two MAb was also observed in some
      endothelial cells in the cortex of the ovary and in the stromal tissue of the
      myometrium, endometrium, and endocervix. These studies suggest that, if
      epithelial ovarian cancers are derived from the surface epithelial cells of the
      ovary, a small proportion of the cancers might be expected to retain the
      phenotype found in non-cancerous cells and to express P-glycoprotein.

PMID- 1976676
TI  - Antigenic cross-reactivity among isolates of group JK corynebacteria.
AB  - Using rocket and rocket-line immunoelectrophoresis and immunoblotting it was
      demonstrated that a group of antibiotic-resistant bacteria, including several
      authenticated Corynebacterium jeikeium strains, shared many cross-reacting
      antigens. Only weak cross-reactivity was demonstrated with representatives of
      three other skin corynebacteria, C. bovis, C. hofmanii and C. minutissimum or
      with non-coryneforms. Differences within C. jeikeium are sufficient to permit the
      use of immunoblotting as an epidemiological tool.

PMID- 1976675
TI  - Beta-lactamase-negative, methicillin-resistant Staphylococcus aureus in a newborn
      nursery: report of an outbreak and laboratory investigations.
AB  - An outbreak of skin infection caused by a beta-lactamase-negative strain of
      methicillin-resistant Staphylococcus aureus (MRSA) occurred during a five-week
      period in a newborn nursery. Twelve babies, two mothers and two members of staff
      were involved. One baby had a diagnosis of staphylococcal scalded skin syndrome
      and two others required treatment with antibiotics. The infecting strain produced
      exfoliative toxin A. It was thought that it had been introduced from a different
      maternity unit by a nasal carrier. Laboratory investigations tended to support
      this hypothesis.

PMID- 1976677
TI  - Surgical wound dressings as barriers to an enveloped virus.
AB  - To determine their efficacy as barriers to the passage of lipid-enveloped
      viruses, wound dressings were exposed to known concentrations of Semliki Forest
      virus (SFV) at their inner surfaces for varying periods of time. The dressings
      were tested such that their outer surfaces were maintained in either a dry or a
      wet environment. Out of a total of 120 dressings each tested at four time points
      under wet conditions, virus was found to have penetrated on only one occasion.
      Similarly, virus penetration was noted in only a single test out of 442 carried
      out on 59 dressings under dry conditions. The dressings under test thus proved
      highly effective barriers to passage of a lipid enveloped virus.

PMID- 1976678
TI  - Hygienic hand disinfection tests in three laboratories.
AB  - A comparative study was made in three laboratories of a test for hygienic hand
      disinfection. Staphylococcus aureus was applied to the fingertips of a total of
      74 volunteers (49 female and 25 male) and the effect of washing with three
      chlorhexidine preparations and one non-medicated soap was assessed after one and
      five applications. Fingertip inoculation is convenient and is a realistic
      representation of the in-use situation. Although significant differences were
      obtained between log10 reductions in test organisms using the same formulation in
      different centres, and different periods in the same centre, the maximum
      differences after a single application of a preparation were small, e.g. between
      centres 0.39 and between periods in the same centre 0.55, and after multiple
      applications the maximum difference between centres was 0.42 and between periods
      in the same centre it was 0.51. The differences between preparations were similar
      in all centres. This test compares well with other similar tests and products can
      be placed in rank order of effectiveness. It is concluded that this test, if
      carried out under the controlled conditions described, is sufficiently
      reproducible between laboratories and repeatable within laboratories to be used
      as a standard test.

PMID- 1976679
TI  - A multi-centre evaluation of two chlorhexidine-containing formulations for
      surgical hand disinfection.
AB  - Many experimental methods have been used to assess the efficacy of products
      intended for surgical hand disinfection. In this study, a modification of the
      Peterson glove juice method was used to compare two chlorhexidine-based surgical
      hand disinfectants, 'Hibiscrub' and an experimental formulation, F.6115. The
      study was performed by four independent laboratories and data merged for
      analysis. There was found to be no significant difference between the two
      formulations. The results illustrate that this modified Peterson glove juice
      method has the potential to form the basis of a standard method for testing
      surgical hand disinfectants which is both relevant to the practical situation and
      reproducible in different laboratories.

PMID- 1976680
TI  - Surgical hand disinfection: effect of sequential use of two chlorhexidine
      preparations.
AB  - The antimicrobial efficacy of three 'two-phase' surgical hand disinfection
      procedures was compared, in a volunteer study, to 60% n-propanol, applied for 5
      min, which is the reference hand-disinfection procedure used in Austria and West
      Germany (FRG). The procedures involved sequential use of unmedicated soap or a
      disinfectant-detergent containing 4% chlorhexidine gluconate (CHX; 'Hibiscrub')
      followed by a handrub preparation containing 70% w/w isopropanol plus 0.5% CHX
      ('Hibisol'). The immediate and sustained effects (3 h) of washing with
      unmedicated soap (3 min) followed by rubbing on 'Hibisol' (4 min) were
      significantly smaller (log10 reductions of 1.72 and 1.12) than with each of the
      other procedures. Use of 'Hibiscrub' (3 min) and 'Hibisol' (4 min) produced log10
      reductions of 2.50 and 1.71, equalling those of the reference procedure with n
      propanol (2.49 and 1.78). When 'Hibisol' was used for 5 min rather than 4 min, a
      considerable, though not significant, increase in effect was achieved (log10
      reductions of 2.90 and 2.07). Replacement of unmedicated soap by 'Hibiscrub'
      could significantly improve the effectiveness of the hand disinfection procedure
      commonly used by surgeons in German-speaking countries; namely to wash hands
      first with soap and then disinfect them with an alcoholic preparation. It may
      also be of additional advantage as this adds another 'layer' of CHX when
      'Hibisol' rather than alcohol alone is used.

PMID- 1976681
TI  - Quantitative determination of endotoxins on surgical gloves.
AB  - The amount of endotoxin on surgical gloves was investigated by the limulus
      chromogenic substrate method. Heavy endotoxin contamination was observed on the
      outside of certain surgical gloves sold in Sweden. Given an endotoxin absorption
      of 10% to the patients, one of the types of gloves studied would cause fever,
      chills, headache and muscle pain. The amount of endotoxin on the gloves could be
      minimized by rinsing in endotoxin-free water. We conclude that the manufacturing
      process of latex gloves should be checked microbiologically for Gram-negative
      bacteria before sterilization. Alternatively, the amount of endotoxin should be
      checked on the product by the limulus ameobocyte lysate test before release.

PMID- 1976682
TI  - Ciprofloxacin-resistant methicillin-sensitive Staphylococcus aureus.

PMID- 1976683
TI  - Enterobacter cloacae in a leukaemic patient.

PMID- 1976684
TI  - Streptococcus pyogenes: an outbreak on a burns unit.

PMID- 1976685
TI  - Hepatitis B carriage rate in patients involved in inoculation injuries and
      implications for post-exposure prophylaxis.

PMID- 1976686
TI  - Handwashing with chlorhexidine gluconate products.

PMID- 1976687
TI  - Emission of viable bacteria in the exhaust flue from a waste incinerator.

PMID- 1976688
TI  - Ritual sprinkling as a source of hospital-acquired infection.

PMID- 1976689
TI  - The role of antiseptics in the management of patients undergoing short-term
      indwelling bladder catheterization.

PMID- 1976690
TI  - Hybrid or multifactorial drugs in antihypertensive treatment.

PMID- 1976691
TI  - Structural alterations of the renin gene in stroke-prone spontaneously
      hypertensive rats: examination of genotype-phenotype correlations.
AB  - Primary hypertension is considered a polygenic, inherited disorder; to date, the
      nature of the genes involved remains unknown. In this study we present evidence
      for a structural difference in the gene coding for renin between the stroke
      prone, spontaneously hypertensive rat (SHRSP) and its normotensive control, the
      Wistar-Kyoto rat (WKY). Restriction fragment analysis using hybridization against
      probes complementary to defined regions of the renin gene identified a deletion,
      approximately 700 base pair in size, within the first intron in SHRSP compared
      with WKY. This restriction fragment length polymorphism (RFLP) affects a part of
      the gene that is characterized by the presence of a multimeric tandem repeat
      element, where the occurrence of insertional/deletional events might be expected
      and have recently been shown in other rat strains. In order to test for a
      possible phenotypical representation of this RFLP, we studied a population (n =
      115) of F2 hybrid rats derived from cross-breeding SHRSP with WKY. Using direct
      blood pressure measurements in conscious animals, we ruled out a cosegregation of
      systolic or diastolic blood pressure with renin genotype. Several other
      phenotypical parameters examined (heart rate, absolute and relative magnitude of
      changes in blood pressure induced by stress or dietary sodium loading, plasma
      renin activity, ventricular hypertrophy and tissue water content) also showed no
      cosegregation with genotype. Our findings are in contrast to a recently published
      study examining an RFLP of the renin gene distinguishing salt-sensitive and salt
      resistant Dahl rats. Thus, cosegregation of genotype and phenotype are not
      consistent, although in both cases, structural differences in the same region of
      the renin gene separate the hypertensive strain from its normotensive controls.
      These data may suggest differential roles of the renin-angiotensin system in
      these two models of genetically predetermined hypertension.

PMID- 1976693
TI  - T lymphocytes that express CD4 and the alpha beta-T cell receptor but lack Thy-1.
      Preferential localization in Peyer's patches.
AB  - Thy-1- T cells expressing CD4 and the alpha beta-TCR have been identified in
      murine lymphoid tissues. These cells are particularly prevalent in Peyer's
      patches (PP), representing 17 +/- 3% of PP CD4 T cells, whereas they are much
      less prevalent in spleen, lymph nodes, lamina propria, or peritoneum. Phenotypic
      studies of fresh-isolated PP T cells demonstrate that all PP CD4 T cells (both
      Thy-1- and Thy-1+) express CD3, alpha beta-TCR, and CD5 (Lyt-1), whereas none
      coexpress CD8 (Lyt-2). Thy-1- and Thy-1+ CD4 T cell lines generated from PP also
      coexpress CD3 and alpha beta-TCR, but are heterogeneous in expression of CD5 and
      again do not coexpress CD8. Further studies revealed that Thy-1- CD4+ T cells
      were not present in nude mice. Short term stimulation of Thy-1+ CD4+ PP T cells
      with anti-CD3 resulted in loss of Thy-1 in a substantial fraction of these cells.
      Functional studies of Thy-1- and Thy-1+ CD4+ PP T cells indicate that fresh
      isolated Thy-1- CD4+ cells do not proliferate in response to insoluble anti-CD3
      but do proliferate when stimulated with soluble anti-CD3 in the presence of
      feeder cells. In contrast, Thy-1+ CD4+ cells proliferate well to both stimuli.
      However, Thy-1- CD4+ PP T cells adapted to in vitro culture exhibit vigorous
      proliferative responses when stimulated with either form of anti-CD3. Evaluation
      of lymphokine secretion by fresh-isolated Thy-1- and Thy-1+ CD4+ PP T cells
      revealed that both make substantial amounts of IL-2; however, Thy-1- T cells made
      less IL-4 than their Thy-1+ counterparts. Neither population made IL-5 or IFN
      gamma. Similarly, Thy-1- and Thy-1+ CD4 T cell lines made similar amounts of IL
      2; again Thy-1- T cells made less IL-4; and in this case Thy-1- T cells made IL-5
      albeit significantly less than the Thy-1+ cells. Finally, immunohistochemical
      studies suggested that many of the CD4+ T cells in PP germinal centers were Thy-1
      , indicating that Thy-1- and Thy-1+ CD4 T cells differ in their distribution
      within the PP. These studies thus define a phenotypically and functionally
      distinct T cell population which is most prevalent in murine Peyer's patches.

PMID- 1976692
TI  - Involvement of the multilineage CD38 molecule in a unique pathway of cell
      activation and proliferation.
AB  - We report clear evidence that the interaction of the CD38 molecule with the
      specific mAb A10 on normal human cells and lines modulates the expression of
      surface activation markers relevant to T, NK, and plasma cell biology and
      functions. Moreover A10 mAb binding is followed by proliferation effects on all
      the target cells analyzed, and the phenomenon is accessory cell and IL-2
      dependent. The effects of A10 mAb synergizing both CD2 and CD3 activation
      pathways indicate that CD38 signal transduction mechanism(s) are apparently
      different from the aforementioned. Nevertheless the decreased A10-driven
      proliferation after CD3-Ti modulation suggests a possible functional
      interdependence between these activation pathways. Taken together, the results
      indicate that the CD38 molecule might play a physiologic role in T, NK, and
      plasma cell regulation.

PMID- 1976694
TI  - CD8+ suppressor T cell clone capable of inhibiting the antigen- and anti-T cell
      receptor-induced proliferation of Th clones without cytolytic activity.
AB  - A CD8+ Ts clone 13G2 was established from lymph node cells of bovine alpha s1
      casein-primed C57BL/6 mice by in vitro antigenic stimulation followed by
      maintenance with IL-2-containing medium. The clone suppressed the Ag-induced
      proliferative responses of CD4+ Th cell clones without detectable cytotoxicity
      for both APC and responding T cells. The clone was able to suppress the in vitro
      proliferative response and antibody formation of Ag-primed lymph node cells. The
      suppression was Ag-nonspecific and not restricted to the MHC. The clone was able
      to suppress the proliferation of Th clones induced by an immobilized anti-TCR
      antibody in which APC was absent. The clone was, however, unable to suppress the
      proliferation of Th clones induced by anti-CD3 or IL-2. Thus, the mechanism of
      suppression by 13G2 was found to be due to a direct action on Th by inhibiting a
      consequence of signal transduction initiated through the TCR.

PMID- 1976695
TI  - Activation of tyrosine phosphorylation in human T cells via the CD2 pathway.
      Regulation by the CD45 tyrosine phosphatase.
AB  - In this study we compare the effect of CD3 and CD2 ligation on tyrosine kinase
      activation in human peripheral blood T cells. Using antiphosphotyrosine antibody
      to detect tyrosine phosphorylation of cellular substrates, we demonstrate that
      mAb stimulation of either CD3 or CD2 results in tyrosine phosphorylation of the
      TCR-zeta chain and 135- and 100-kDa proteins. However, differences are observed
      between CD3 and CD2 ligation; only the former results in rapid tyrosine
      phosphorylation of 72-, 65-, and 40-kDa substrates. Co-aggregation of CD2 and
      CD45, a tyrosine phosphatase, results in inhibition of intracellular calcium
      elevation and T cell proliferation. We demonstrate in this study that this
      manipulation also inhibits polyphosphoinositide hydrolysis and tyrosine
      phosphorylation of the 100-kDa substrate. The failure of tyrosine phosphorylation
      of the 100-kDa substrate is specific in that phosphorylation of the 135-kDa
      protein is not inhibited. Similar results are observed when CD2 and CD45 are
      independently cross-linked rather than co-aggregated. The observation that CD45
      cross-linking alters tyrosine phosphorylation of T cell substrates and effects
      polyphosphoinositide hydrolysis is further evidence that tyrosine phosphorylation
      regulates early events in T cell activation including, perhaps, phospholipase C
      activity.

PMID- 1976696
TI  - Loss of epidermal integrity by T cell-mediated attack induces long term local
      resistance to subsequent attack. II. Thymus dependency in the induction of the
      resistance.
AB  - Our previous study showed that in cutaneous graft-vs-host disease (GVHD) induced
      by intradermal injection of autoreactive T cells the epidermal structures
      spontaneously recovered from the destruction became resistant to the subsequent
      attempts to induce the cutaneous GVHD and that the resistance correlated well
      with a 30-fold increase in the number of Thy-1+ epidermal cells (Thy-1+EC). We
      show that the resistance to the cutaneous GVHD was never induced in athymic nude
      mice and adult thymectomy lethal radiation and bone marrow reconstitution (ATXBM)
      mice under the same conditions, indicating that the induction of the resistance
      is dependent on the presence of thymus. A great increase in the number of Thy
      1+EC was similarly observed in the epidermis of the athymic nude and ATXBM mice
      that spontaneously recovered from the cutaneous GVHD and that remained
      susceptible to the induction of the cutaneous GVHD. However, the results with
      B10Thy-1.1----B6 radiation chimeras clearly demonstrate that the vast majority of
      the increased Thy-1+EC found in the "susceptible" epidermis of the ATXBM mice
      were of donor bone marrow origin and there was no increase in the number of host
      derived Thy-1+EC, whereas in the "resistant" epidermis of the XBM mice both Thy
      1+EC populations were equally increased. The overall results indicate that the
      expansion of Thy-1+EC that mature in the thymus is crucial to the induction of
      the resistance, although the migration of bone marrow-derived Thy-1+EC precursors
      to the epidermis occurs quite independently of the presence of thymus.

PMID- 1976697
TI  - Distinct adhesive properties of granulocytes and monocytes to endothelial cells
      under static and stirred conditions.
AB  - Adherence of neutrophils and monocytes to endothelium is an important event in
      the sequence of leukocyte responses to inflammatory disease. Double-color flow
      microfluorimetry analysis was used to determine neutrophil and monocyte adherence
      to suspended endothelial cells under stirred conditions. The static adherence to
      endothelial cell monolayers was simultaneously determined. In both assays,
      neutrophils behaved in a similar way. Basal adherence of neutrophils was very
      low. Activation by PMA or by the chemoattractants platelet-activating factor and
      FMLP induced rapid binding, primarily mediated by CR3. Nonactivated neutrophils
      showed CD18-dependent (lymphocyte function-associated Ag-1 and CR3) and CD18
      independent adherence to endothelial cells when the endothelial cells were
      prestimulated with rIL-1 beta. In contrast to neutrophils, nonactivated monocytes
      adhered avidly to resting endothelial cells. This adherence was partly CD18
      dependent and partly CD18 independent. Whereas monocyte adherence under stirred
      conditions strongly increased upon activation by PMA, a significant decrease in
      adherence was found under static conditions, which was prevented by cytochalasin
      B. This decrease was limited to a distinct CD18-independent binding mechanism,
      and absent under stirred conditions. We conclude that monocytes adhere with (at
      least) three binding mechanisms to endothelial cells, a CD18-dependent and two
      CD18-independent mechanisms.

PMID- 1976698
TI  - Two pathways of CD11b/CD18-mediated neutrophil aggregation with different
      involvement of protein kinase C-dependent phosphorylation.
AB  - The characteristics of homotypic neutrophil aggregation, mediated by the adhesion
      molecule CD11b/CD18, differ according to whether activation takes place via
      intracellular protein kinase C(PKC) inducers or chemoattractants. In response to
      diacylglycerol (DAG) analogues such as PMA and 1,2-dioctanoyl-sn-glycerol, a
      prolonged cellular aggregation occurs that is associated with intense
      phosphorylation of the CD18 beta-chain. In response to the chemoattractant FMLP,
      a more transient aggregation event results that is associated with minimal beta
      chain phosphorylation. By using the PKC inhibitor staurosporine, we now show that
      these differences are likely to reflect two different pathways of activation.
      Both aggregation and phosphorylation induced by DAG analogues are completely
      abolished by staurosporine in a parallel dose-dependent manner. Conversely, FMLP
      induced aggregation is enhanced and prolonged by staurosporine whereas the
      associated minimal phosphorylation event is further diminished by staurosporine.
      Accordingly, activation of neutrophil aggregation by DAG analogues is associated
      with and presumably due to phosphorylation of the CD18 beta-chain. This intense
      phosphorylation occurs via a staurosporine-sensitive kinase such as PKC. FMLP, on
      the other hand, appears to activate CD11b/CD18 by a distinct mechanism. This
      latter mechanism does not seem to be dependent on what may be a minor PKC-induced
      phosphorylation of the beta-chain, and indeed is enhanced by inhibition of PKC.
      Of note, staurosporine was also found to cause selective release of specific
      granules with concomitant increase in surface display of CD11b/CD18. These data
      further support previous observations that up-regulation of this adhesive
      molecule is not the primary event in the induction of cellular adhesiveness.

PMID- 1976699
TI  - Delineation of the mechanism of inhibition of human T cell activation by PGE2.
AB  - The capacity of PGE2 to inhibit human T cell responses was examined by
      investigating its effect on mitogen-induced IL-2 production and proliferation of
      highly purified CD4+ T cells. PGE2 inhibited both PHA and anti-CD3 induced
      proliferation and IL-2 production by an action directly on the responding T cell.
      Inhibition of IL-2 production reflected decreased accumulation of mRNA for IL-2.
      A variety of other cAMP elevating agents exerted similar inhibitory effects.
      Inhibition of proliferation could be overcome by supplemental IL-2, PMA, or the
      anti-CD28 mAb 9.3. Although PMA and 9.3 markedly increased the amount of IL-2
      produced by mitogen-stimulated T cells, the percentage inhibition of IL-2
      secretion caused by PGE2 and other cAMP elevating agents remained comparable in
      these costimulated cultures. Rescue of T cell DNA synthesis by these agents
      appeared to reflect the finding that, although PGE2 markedly inhibited IL-2
      production, the absolute amount of IL-2 produced was increased sufficiently to
      sustain mitogen-induced proliferation. As anticipated, PGE2, forskolin, and
      cholera toxin increased T cell cAMP levels. The quantity of cellular cAMP
      generated in response to PGE2, cholera toxin, and forskolin could be inhibited by
      PMA or 2',5'-dideoxyadenosine. Using these reagents, the inhibitory effects of
      PGE2 were found to reflect intracellular cAMP levels, but only within a very
      narrow range. The results indicate that by elevating cAMP levels, PGE2 inhibits
      human T cell IL-2 production at a point that is common to both the CD3 and CD28
      signaling pathways.

PMID- 1976700
TI  - Evidence that a receptor-operated event on the neutrophil mediates neutrophil
      accumulation in vivo. Pretreatment of 111In-neutrophils with pertussis toxin in
      vitro inhibits their accumulation in vivo.
AB  - The role of neutrophil chemoattractant receptors in neutrophil stimulation in
      vitro is well established, however, the precise mechanisms underlying local
      neutrophil accumulation at inflammatory sites in vivo have not been defined. A
      fundamental question that remains open is whether chemoattractants act on the
      endothelial cell or the neutrophil to initiate the process of neutrophil
      migration in vivo. To address this question we have investigated whether
      neutrophil accumulation in vivo can occur if chemoattractant receptor occupancy
      is uncoupled from neutrophil stimulation. For this purpose we have used pertussis
      toxin (PT) as the pharmacologic tool. We have investigated the effect of in vitro
      pretreatment of rabbit neutrophils with PT on their responses in vitro and on
      their accumulation in vivo. Pretreatment of rabbit neutrophils with PT inhibited
      FMLP- and C5a-, but not PMA- induced increases in CD18 expression, neutrophil
      adherence, and degranulation in vitro. This pretreatment procedure with PT
      inhibited the accumulation of radiolabeled neutrophils in vivo in response to
      intradermally injected FMLP, C5a, C5a des Arg, leukotriene B4, IL-8, and zymosan
      in rabbit skin. Further, in contrast to the in vitro results, PT inhibited the
      PMA-induced 111In-neutrophil accumulation in vivo. Interestingly, pretreatment of
      neutrophils with PT also inhibited accumulation in response to intradermally
      injected IL-1, despite the reports that IL-1 lacks neutrophil chemoattractant
      activity in vitro. Although the experimental techniques used cannot distinguish
      the different stages of neutrophil migration involved, these results suggest that
      the accumulation of neutrophils induced by local extravascular chemoattractants
      in vivo depends on a pertussis toxin-sensitive receptor operated event on the
      neutrophil itself. Further, PMA and IL-1 may release secondary chemoattractants
      in vivo.

PMID- 1976702
TI  - Characterization of new mouse V kappa groups.
AB  - A lambda gt10 BXSB spleen cDNA library was screened with a DNA probe for the C
      kappa region. Forty individual C kappa+ phages were tested for hybridization with
      DNA probes representing 11 V kappa region groups. Of the phage inserts large
      enough to contain V kappa region sequences, 3 were negative for hybridization
      with all 11 V kappa region probes. The inserts from those three were subcloned,
      sequenced, and compared with V kappa region sequences in the gene bank. One was
      identical to 87.92.6 for the region sequenced (a member of V kappa RF). The
      second showed 93.8% sequence similarity with AN04 and called V kappa 32. The
      third called V kappa 33 showed 76% sequence similarity with the human sequence
      V52 and 73.2% sequence similarity with the mouse sequence L6. An insert from V
      kappa 32 containing the 5' untranslated regions through the codon for Cys 88 of
      the V kappa region was used as a probe in Southern blot analysis of genomic DNA
      from inbred and congenic strains of mice. V kappa 32 is a four to eight member
      group and some of the members are retained in the B6.PL-Ly2a congenic and missing
      from the B6.PL (85NS) congenic consistent with a map location near V kappa 28.
      The same filters were hybridized with the insert from V kappa 33 containing 5'
      untranslated region through the codon for Ser 93 of the V kappa region. V kappa
      33 is a one to three member group and using the B6.PL congenics maps with the
      polymorphic fragments of V kappa 32 and V kappa 28.

PMID- 1976701
TI  - Regulation of HIV replication in infected monocytes by IFN-alpha. Mechanisms for
      viral restriction.
AB  - In a survey of 15 different virus isolates, no IFN-alpha or IFN-beta activity was
      detected in culture fluids of HIV-infected T cells or monocytes. Exogenous rIFN
      alpha added to T lymphoblast or monocyte cultures induced restriction in
      replication of the amphotropic HIV that infect both cell types. With IFN-treated
      HIV-infected T cells, levels of reverse transcriptase (RT) activity in culture
      fluids were half those in control cultures, but the frequency of infected cells
      or the levels of p24 Ag released in culture fluids were unchanged. In contrast to
      the modest effect of IFN on HIV-infected T cells, IFN-induced antiviral activity
      in monocytes was quite dramatic. Monocytes treated with IFN at the time of virus
      challenge showed no evidence of HIV infection: no p24 Ag or RT activity, no viral
      mRNA, and no proviral DNA. In this system, IFN interrupts one or more early
      event(s) in the virus replication cycle before formation of proviral DNA.
      Monocyte cultures infected with HIV 7 days before IFN treatment showed a gradual
      decrease in levels of p24 Ag and RT activity to baseline by 3 wk. HIV-induced
      cytopathic changes were markedly reduced, and the frequency of productively
      infected cells was less than or equal to 1% of total cells. Virus particles
      released 24 h after IFN treatment were 100- to 1000-fold less infectious than
      equal numbers of control virions. But, monocytes treated with IFN 7 days after
      HIV infection were not free of the retroviral pathogen: levels of proviral DNA in
      the IFN-treated and control HIV-infected cells were indistinguishable. The
      presence of large quantities of proviral DNA in cells with little or no evidence
      for active transcription documents a situation approaching true microbiological
      latency.

PMID- 1976703
TI  - Prevalence and polymorphism of human VH3 genes.
AB  - To better understand heterogeneity of human VH genes, we have studied
      polymorphism among three homologous genes from VH3, the most complex human VH
      gene family. Sequence-specific oligonucleotide probes were used to identify the
      germ-line source of each gene. The fetally expressed gene 56p1, and the germ-line
      VH element 1.9III, were identified and shown to be distinct. Also identified was
      T5M10, a VH element that resembles 56p1 and 1.9III, and likely corresponds to the
      previously described germ-line gene, hv3005. The elements 56p1, 1.9III, and T5M10
      were each polymorphic, and in 52 unrelated individuals, their prevalences were
      62%, 92%, and 35%, respectively. Among individuals lacking the hybridization
      bands characteristic of 56p1, 1.9III, or T5M10, alternative RFLP or coding region
      sequence variants were not found. In the population studied, these three VH
      elements were present in five different combinations, and at least three
      haplotypes. The distribution of these VH elements indicated they are not alleles
      of a single locus, and 56p1 and 1.9III are probably not alleles of each other.
      These results suggest that polymorphism is commonplace among human VH3 genes, but
      that a limited number of conserved alleles dominate each locus. We conclude that
      heterogeneity in the VH germ-line repertoire may derive more from diversity of
      haplotypes than from diversity of alleles.

PMID- 1976704
TI  - In vitro differentiation from a pluripotent human CD4+CD8+ thymic cloned cell
      into four phenotypically distinct subsets.
AB  - Human thymic cell differentiation is almost totally unknown. In the present study
      we developed an in vitro system using human thymic cloned cells to analyze
      precursor-progeny relationship. We obtained several CD4+CD8+ double positive
      thymic clones that could give rise after several weeks in culture only to either
      CD4 or CD8 single positive clones. By contrast we isolated a unique pluripotent
      thymic double positive clone, termed B12, which differentiated into four
      phenotypically distinct T cell clones, namely double-positive CD4+CD8+, double
      negative CD4-CD8- or either single-positive phenotype. We derived stable
      subclones representative of each phenotype and we showed by molecular analysis
      that they expressed the same TCR. Utilization of either CD3 or anticlonotypic mAb
      revealed that this TCR expressed by the four subclones was functional.

PMID- 1976705
TI  - Heterogeneity of helper/inducer T lymphocytes. III. Responses of IL-2- and IL-4
      producing (Th1 and Th2) clones to antigens presented by different accessory
      cells.
AB  - Murine CD4+ T cell clones have been classified into at least two subsets, Th1 and
      Th2, on the basis of their distinct lymphokine secretion profiles and functions.
      In the present study, we compared the functional responses of Th1 and Th2 clones
      to Ag presentation by splenic B cells and peritoneal macrophages. Th2 clones
      secreted IL-4 in response to Ag presented by resting B cells, but their optimal
      proliferation required the addition of IL-1 or a source of IL-1. The degree of IL
      1 dependence varied among the four Th2 clones examined. In contrast, Th1 clones
      secreted IL-2 and proliferated in response to Ag presented by both B cells and
      macrophages, without any requirement for exogenous IL-1. Furthermore, the
      proliferation of Th2 clones in response to Ag presented by splenocytes or
      macrophages was inhibited by an IL-1R antagonist. These results indicate that IL
      1 is an important costimulator for the expansion of the Th2 subset of CD4+ T
      cells. The different requirements for the proliferation of Th1 and Th2 cells may
      be responsible for the preferential expansion of one or the other subset under
      different conditions of immunization.

PMID- 1976706
TI  - In vivo ultraviolet-exposed human epidermal cells activate T suppressor cell
      pathways that involve CD4+CD45RA+ suppressor-inducer T cells.
AB  - In vivo UV exposure of human epidermis abrogates the function of CD1+DR+
      Langerhans cells and induces the appearance of CD1-DR+ Ag-presenting macrophages.
      Epidermal cells from UV-exposed skin, in contrast to epidermal cells from normal
      skin, potently activate autologous CD4+ T cells, and, in particular, the CD45RA+
      (2H4+) (suppressor-inducer) subset. We therefore determined whether UV-exposure
      in humans leads to a T cell response in which suppression dominates. Autologous
      blood T cells were incubated with epidermal cell suspensions from in vivo UV
      irradiated skin. After activation, repurified T cells were transferred in graded
      numbers to autologous mononuclear cells (MNC) stimulated with PWM and the
      resultant IgG production analyzed by ELISA. Relative to T cells activated by
      unirradiated control epidermal cells, T cells activated by UV-exposed epidermal
      cells demonstrated enhanced capacity to suppress IgG production (n = 6; p less
      than or equal to 0.03). Within the T cell population, CD8+ cells stimulated by UV
      exposed epidermal cells could be directly activated to suppress PWM-stimulated
      MNC Ig production if IL-2 was provided in the reaction mixture. The suppressive
      activity was also transferable with purified CD4+ T cells stimulated by UV
      exposed epidermal cells (n = 10; p less than or equal to 0.01), and was
      radiosensitive. Suppression was decreased when PWM-stimulated MNC were depleted
      of CD8+ T cells before mixing with CD4+ T cells activated by UV-exposed epidermal
      cells, suggesting indirect induction of CD8+ Ts cells contained within the
      responding MNC populations. Indeed, physical depletion of CD45RA+ cells resulted
      in total abrogation of the suppressor function contained in the CD4+ T cells.
      Activation of suppressor function was critically dependent on DR+ APC contained
      in UV-exposed epidermis. The data suggest that UV-exposure modulates cutaneous
      APC activity in humans, as in mice, such that the dominant immune response is
      tilted toward suppression. These mechanisms in normal individuals may function to
      dampen responses to UV-induced endogenous Ag that are pathogenic in autoimmune
      disorders. However, these mechanisms might also facilitate the growth of UV
      induced skin cancers.

PMID- 1976707
TI  - Intact antigen receptor-mediated generation of inositol phosphates and increased
      intracellular calcium in CD4 CD8 T lymphocytes from MRL lpr mice.
AB  - The predominant T lymphocytes that accumulate in the peripheral lymphoid tissues
      of mice homozygous for the lpr gene bear the phenotype CD3+CD4-CD8-. By certain
      functional criteria these cells would appear to have impaired CD3-mediated signal
      transduction, in that they do not respond to alloantigen and produce little if
      any detectable IL-2 or other lymphokines. However, the signal pathway appears
      adequate for achieving other T cell functions, including induction of high
      affinity IL-2R, and thymic deletion. To clarify the basis of this seeming
      discrepancy, we examined transmembrane signal transduction in T cell subsets of
      lpr/lpr (lpr) and +/+ mice, as defined by increased [Ca2+]i and the generation of
      inositol phosphates (InsPs). Stimulation of lpr CD4-CD8- cells with anti-CD3
      antibody produced prompt and sustained increases in the concentration of [C2+]i
      and in InsPs. Similar responses occurred in mature T cells from lpr and +/+ mice,
      except for the somewhat slower kinetics of their increased [Ca2+]i. In marked
      distinction to the anti-CD2-mediated response, Con A, even in high doses, could
      not stimulate any increase of [Ca2+]i in lpr CD4-CD8- cells, and only modest
      increases in InsPs. Mature T cells, whether of lpr or +/+ origin, yielded normal
      increased [Ca2+]i with Con A. The reason for the differences in signal
      transduction between anti-CD3 and Con A stimulation of lpr CD4-CD8- cells may
      relate to the absence of surface structures on these immature T cells that are
      required for activation by Con A but not by anti-CD3. The data demonstrate that
      the CD3 complex in lpr CD4-CD8- T cells can couple to phospholipase C to
      hydrolyze phosphoinositides. These activation properties of lpr CD4-CD8- T cells
      have interesting functional parallels to thymocytes at the time of thymic
      selection, as well as tolerance induction of mature T lymphocytes.

PMID- 1976708
TI  - Characterization of the CD45 molecule on murine intestinal intraepithelial
      lymphocytes.
AB  - The CD45 molecule was analyzed from murine intestinal intraepithelial lymphocytes
      (IEL). Immunofluorescent staining of CD8+ IEL revealed varying degrees of
      reactivity with mAb specific for CD45-restricted determinants, some which are
      typically expressed only by B cells. Immunoprecipitation of CD45 molecules from
      IEL yielded an array of proteins with apparent (m.w.) ranging from 180,000 to
      260,000. The m.w. 260,000 form was restricted to IEL, was distinct from the B220
      molecule, and was the only CD45 isoform that expressed the CD45-associated
      carbohydrate differentiation Ag CT1. Moreover, the CT1 determinant was present on
      cells of the Thy-1- but not the Thy-1+ IEL subset. Sequential immunoprecipitation
      studies indicated that expression of the m.w. 260,000 protein was not restricted
      to CT1+ cells. The protein composition of the m.w. 260,000 CD45 isoform was
      examined by using the polymerase chain reaction for analysis of CD45 variable
      exon usage. In contrast to B cells in which the major CD45 mRNA contained all
      three variable exons (exons 4, 5, and 6), IEL CD45 mRNA contained significant
      amounts of two-exon, single exon, and zero variable exon forms. Restriction
      enzyme analysis identified the single exon form as exon 5 and the two-exon form
      as a mixture of exons 4 and 5 and exons 5 and 6. Metabolic labeling of CD45 in
      pulse-chase experiments suggested that the generation of this high m.w. protein
      was caused by post-translational modifications, perhaps glycosylation. Overall,
      the results indicated that the high m.w. form of CD45 and the addition of the CT1
      determinant were generated via IEL-specific post-translational modifications and
      not by novel alternate exon usage.

PMID- 1976709
TI  - Immunologic responsiveness in American cutaneous leishmaniasis lesions.
AB  - American cutaneous leishmaniasis is a disease of skin and mucous membranes in
      which T lymphocytes reactive to Leishmania (Viannia) braziliensis are thought to
      contribute to protective immunity. To characterize the nature of the T cell
      inflammatory infiltrate in American cutaneous leishmaniasis lesions,
      immunohistochemistry with mAb that define T cell subpopulations and in situ
      hybridization to detect mRNA coding for IFN-gamma were performed. In both
      localized cutaneous (LCL) and mucocutaneous (MCL) lesions, we observed a
      predominance of T memory (CD4+CD45RO+) as compared to T naive cells (CD+CD45RA+).
      The percentages of cells containing IFN-gamma mRNA were equivalent in both LCL
      and MCL lesions. T cells were extracted from LCL and MCL lesions and analysis
      indicated that T cells from both lesions had been stimulated by L. (V.)
      braziliensis in vivo and gave equivalent proliferative responses in vitro. The
      present data suggest that T memory cells, which are likely to elaborate IFN
      gamma, are components of DTH response to L. (V.) braziliensis and participate in
      the pathogenesis of both LCL and MCL lesions.

PMID- 1976710
TI  - An investigation of the T cell requirements of in vitro antibody forming B cells
      detected by the ELISPOT assay and a comparison with antibody synthesis.
AB  - We have studied the primate cellular requirements in the antibody forming cell
      (AFC) assay, using a 185,000 molecular mass streptococcal antigen. Cultures of B
      cells alone stimulated with the antigen were unable to develop into AFC.
      Reconstitution of B cells with T cells resulted in a significant increase in the
      number of AFC. However, CD4 cells were more efficient than T cells in helping the
      antibody response and CD8 cells failed to induce B cells to synthesise antibody.
      A comparison between the specific IgG antibody synthesis and the number of AFC
      detected by the ELISPOT method showed a highly significant correlation between
      the number of AFC and the amount of specific IgG antibody. We suggest that the
      AFC (ELISPOT) assay can be readily used to investigate B cell interactions with T
      cell subsets.

PMID- 1976711
TI  - [Role of calcium antagonists in the treatment of chemoresistant cancer of the
      kidney].
AB  - In experimental cell lines and in some human tumors, calcium antagonists reversed
      multidrug resistance in vitro. So far, clinical trials have not been very
      rewarding as intrinsic cardiovascular activities of these compounds impeded a
      sufficient dosage. Renal cell carcinomas are considered to be good models for the
      evaluation of this new therapeutic concept. In 35 primary human renal cell
      carcinomas, the potency of 7 different calcium antagonists in combination with
      vinblastine monotherapy was examined in a tetrazolium-based microculture assay
      (MTT test) in order to circumvent chemoresistance. Substances derived from
      piperazine (flunarizine) showed only minor effects in this respect. The calcium
      antagonists of the papaverine type such as Verapamil etc. revealed the strongest
      reversal of chemo-resistance. Derivatives of benzothiazepine (diltiazem) or of
      dihydropyridine (nifedipine etc.) acted similarly and reached about 70% of the
      Verapamil activity. All calcium antagonists tested lead to significant
      enhancement of vinblastine cytotoxicity. In particular, the new stereoisomer R
      Verapamil, which showed strong reversal of resistance but which exerts 10 times
      lower cardiovascular side effects than racemic Verapamil, seems to be suitable
      for further evaluation with regard to the clinical application.

PMID- 1976712
TI  - [Adherence of Pseudomonas aeruginosa to mouse tracheal epithelium--the effect of
      antimicrobial agents].
AB  - The adherence of bacteria to mucosal surfaces is an important initial event in
      the pathogenesis of most bacterial infectious diseases. In order to clarify the
      mechanism of respiratory tract infections caused by Pseudomonas aeruginosa, we
      paid attention to pili (fimbriae), which is one of the adherence factors for the
      nonmucoid strains of P. aeruginosa. The adherence of P. aeruginosa was studied
      using two mutants: piliated and nonpiliated strains and 0.1 N hydrochloric acid
      injured mouse tracheal epithelium as a respiratory tract model. The adherence
      ability was evaluated by means of direct count of adhered bacteria using a
      scanning electron microscope. The effect of antimicrobial agents was studied on
      the adherence and the production of pili. Both mutants of P. aeruginosa adhered
      more significantly to the acid-injured tracheal epithelium than the normal one (p
      less than 0.01). The number of the piliated strain adhering to the acid-injured
      tracheal epithelium was significantly greater than that of the nonpiliated strain
      (p less than 0.01). The piliated bacteria treated with heat, formalin, antiserum
      against pili, N-acetylneuraminic acid and N-acetylglucosamine showed a
      significant decrease in number of adherence. The piliated bacteria were grown in
      a media containing 1/4 MICs of seven antimicrobial agents for four hours at 37
      degrees C, after that a significant reduction in the number of pili per bacterium
      was recognized with erythromycin, minocycline and clindamycin (p less than 0.01).
      The piliated bacteria treated with erythromycin showed a significant decrease on
      adherence to the acid-injured tracheal epithelium in parallel with
      piliation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1976713
TI  - [An epidemiologic study of anti-ATLA (antibody to adult T-cell leukemia
      associated antigen) by category of disease in the Karatsu and Higashimatsuura
      districts of northern Kyusyu by enzymeimmunoassay].
AB  - The Kyusyu district is known as an endemic area of HTLV-I. But the prevalence of
      anti-ATLA in Saga prefecture was reportedly relatively low. In this study, in
      order to determine the distribution of antibody to ATL-associated antigen (anti
      ATLA) in the Karatsu and Higashimatsuura districts of the northern Kyusyu, the
      determination of anti-ATLA status of patients in Karatsu Red Cross Hospital was
      carried out from September to October, 1985. Sera from 757 patients were tested
      for presence of anti-ATLA by Enzyme immunoassay (EIA) prepared by Eisai Co., Ltd.
      Tokyo, Japan. Results obtained are as follows: 1) Overall prevalence of anti-ATLA
      was 13.7 per cent (104 of 757 individuals). Prevalence of anti-ATLA increased
      with age, reaching a maximum of 21.1 per cent for people from 60 to 69 years old.
      2) Prevalence of anti-ATLA was 9.5 per cent (36 of 376) in males and 17.8 per
      cent (68 of 381) in females. A significant difference by sex was recognized. (p
      less than 0.001) 3) The positive rates of patients with non-malignant diseases
      were high in the Chinzei, Hizen, and Hamatama areas facing the Sea of Genkai. The
      positive rate of the seaside area was significantly higher than that of the
      mountain area. (p less than 0.001). 4) Anti-ATLA was most prevalent in the
      patients with neoplasms (26.1%). The positive rate of ATL patients was 100 per
      cent, and that of patients with malignancies other than ATL was 25.9 per cent.
      These results suggest that HTLV-I infection is likely to increase the incidence
      of other types of malignancy.

PMID- 1976714
TI  - [Clinical results of sequential and "Y" grafting with the internal mammary
      artery].
AB  - One hundred and sixty-five patients (125 men, 40 women; age ranged from 40 to 81
      years), underwent coronary artery bypass grafting in the 3 years period from 1986
      to 1988. The internal mammary artery (IMA) was applied to 125 patients (75.8%).
      The sequential left IMA grafting to the left anterior descending coronary artery
      (LAD) and the diagonal branch (Dg) was performed in 9 out of 125 patients. In 3
      of 9 patients, the right IMA was simultaneously grafted to the obtuse marginal
      branch (OM). In situ bilateral IMAs grafting to the LAD and Dg or LAD and OM were
      used in 13 patients. In three patients, "Y" grafting (the free right IMA was
      anastomosed to the side of the in situ left IMA) was performed for LAD and Dg.
      Eighty-one of 82 IMA grafts (99%) were patent about 1 month after operation.
      Three patients (1.8%) died during hospitalization, one from Low Output Syndrome,
      two from cerebral infarction. Perioperative complication included myocardial
      infarction in 5 (3.0%), cerebral infarction in 10 (6.0%). We concluded that the
      IMA could be applied in multivessel grafting as well as single vessel grafting in
      severe diffuse coronary artery disease in the Japanese, and the early patency was
      good even in the sequential and "Y" grafting.

PMID- 1976715
TI  - [Studies on the immunohistochemical localization of adhesive factors at the site
      of implantation in the early pregnancy].
AB  - We studied the localization of adhesive proteins at the site of implantation in
      mouse pregnancy (5 days' gestation), and human pregnancy (5-8 weeks' gestation)
      and in human endometrial culture cells. Immunohistochemical staining of adhesive
      protein such as fibronectin (FN), laminin, type IV collagen (CIV), subunit A of
      factor XIII (XIIIA), and subunit S of factor XIII (XIIIs) were performed by
      indirect enzyme immunoassay to investigate their localization. (1) In mouse
      pregnancy: FN and XIIIs were stained in trophoblastic giant cells, and CIV was
      stained in the endometrial epithelium. (2) In human pregnancy: (fetal side) CIV
      was stained diffusely on the surface of syncytiotrophoblast. FN, CIV, and XIIIA
      were stained in the stroma of the villi. (maternal side) FN, CIV, and XIIIA were
      stained in the endometrial stroma. (3) In endometrial culture cells: FN and XIIIA
      were stained strongly in the stromal cells. These findings demonstrated that FN
      and XIIIA are produced in the endometrial stromal cells, and suggest that FN,
      CIV, and XIIIA are concerned with the attachment of the embryo to the uterus.
      Therefore, these adhesive proteins are important factors in maintaining
      pregnancy.

PMID- 1976716
TI  - DNA topoisomerases and radiation responses.

PMID- 1976717
TI  - DNA repair in radiation sensitive mutants of mammalian cells: possible
      involvement of DNA topoisomerases.
AB  - Mutants are invaluable in the study of DNA repair processes. The past 10 years
      have seen a rapid proliferation of papers describing the isolation of mammalian
      cell mutants exhibiting DNA repair abnormalities. A variety of DNA-damaging
      agents, including radiation, alkylating agents and bleomycin, have been used to
      select mutants. This mini-review will concentrate on radiation (particularly
      ionizing radiation)-sensitive mutants, whether selected directly on the basis of
      radiation sensitivity or subsequently found to be cross-sensitive to radiation.
      Commonly observed DNA repair defects are associated with sensitivity to
      radiation. For UV-sensitive mutants a defect in the incision step of excision
      repair is frequently seen. For ionizing radiation-sensitive mutants, the common
      feature is a defect in the repair of DNA strand breaks. This may take the form of
      a reduced rate of strand-break rejoining or of a lowering in the fidelity of
      rejoining. Recent work suggests that the DNA topoisomerases may participate in
      the repair of DNA strand breaks and that strand breaks induced by both
      topoisomerase inhibitory drugs and radiation may be repaired by common pathways.

PMID- 1976718
TI  - DNA double-strand breaks: their repair and relationship to cell killing in yeast.
AB  - Yeast is a suitable eukaryotic organism in which to study DNA double-strand
      breakage measured by the neutral sucrose gradient sedimentation technique and
      cell killing in the same range dose of sparsely ionizing radiations.
      Radiosensitive mutants (including temperature conditional ones) exist in which
      rejoining of double-strand breaks (dsb) is not detectable. In such mutants
      approximately one dsb per cell corresponds to a lethal event, suggesting that a
      dsb is a potentially lethal lesion. There are two modes by which dsb may confer
      cell lethality: firstly, an unrepaired dsb may be lethal on its own and secondly,
      two dsb may interact to form a lethal lesion (binary misrepair). The
      operationally defined cellular phenomena of potentially lethal damage (PLD)
      repair and sublethal damage (SLD) repair are both based on the repair of dsb.
      Induced dsb show a linear and unrejoined dsb a linear-quadratic relationship with
      dose. At low dose rate the quadratic component is abolished in accordance with
      the exponential survival curve observed. The dose-rate effect is based on dsb
      repair during irradiation; it is absent in dsb repair-deficient mutants.

PMID- 1976719
TI  - SV40 DNA amplification and reintegration in surviving hamster cells after 60Co
      gamma-irradiation.
AB  - SV40-transformed Chinese hamster embryo cells were exposed to 60Co gamma
      irradiation and the fate of the integrated SV40 sequences was pursued over a
      period of 20 days following radiation exposure. As shown by colony hybridization,
      integrated SV40 sequences were amplified in surviving and non-surviving cells. At
      later times, however, clonal sublines of surviving cells grown for 20-30 cell
      generations after irradiation had lost most of their amplified SV40 copies but
      showed altered restriction fragment patterns indicating reintegration of SV40
      sequences at new sites of the hamster genome. This suggests that 60Co gamma
      irradiation can generate mutations by inducing over-replication of chromosome
      segments that are then substrates of enzymatic rearrangements.

PMID- 1976720
TI  - The influence of glutathione on single-strand breakage in single-stranded DNA
      irradiated in aqueous solution in the absence and presence of oxygen.
AB  - The yields of strand break formation (Gssb) in single-stranded DNA (ssDNA)
      initiated by radiation-generated OH radicals have been determined using the
      method of low-angle laser light scattering (LALLS). The irradiations were carried
      out in aqueous, N2O-saturated solutions in the absence and presence of oxygen and
      at different concentrations of glutathione (GSH). GSH exhibits a protective
      effect, which is shown to be mainly due to OH radical scavenging. To quantify
      this, the rate constants for the reactions of OH with GSH and DNA have been
      redetermined under our experimental conditions. The values obtained were 9.0 x
      10(9) and 4.5 x 10(8) dm3 mol-1 s-1, respectively. From the Gssb values obtained
      under anoxic conditions it is concluded that GSH protects against strand breakage
      (in addition to OH scavenging) by reacting with DNA radicals in competition to
      strand break formation. The rate constant of the repair reaction is 8.1 x 10(4)
      dm3 mol-1 s-1 at room temperature. For irradiations carried out in the presence
      of oxygen the rate of strand break formation is determined by the decay of DNA
      peroxyl radicals. Under these conditions we observed no protective effect of GSH
      apart from OH radical scavenging. The results are compatible with those that are
      expected from the oxygen-fixation hypothesis.

PMID- 1976721
TI  - Determination of the constants of the Alper formula for single-strand breaks from
      kinetic measurements on DNA in aqueous solution and comparison with data from
      cells.
AB  - On the basis of rate constants measured in aqueous solution for (i) DNA single
      strand break (ssb) formation induced by OH radicals, (ii) prevention of ssb
      formation by reaction of DNA radicals with glutathione, and (iii) addition of O2
      to DNA radicals, oxygen enhancement ratios (OER) and K values of the Alper
      equation have been calculated. The values obtained were compared with OER and K
      values determined for ssb formation in lambda DNA irradiated in Escherichia coli
      as a function of the oxygen concentration. Without adjustment of any parameter
      the two sets of data are similar when the corrected Alper formula is used. The
      results support the oxygen fixation-thiol repair model of Howard-Flanders and
      Alper, and indicate that under selected conditions DNA in aqueous solution may
      serve as a model system for DNA in cells.

PMID- 1976722
TI  - Enhancement of radiosensitivity of cultured mammalian cells by neocarzinostatin.
      I. Inhibition of the repair of sublethal damage.
AB  - The enhancement of radiosensitivity by neocarzinostatin (NCS), an antitumour
      drug, was studied using three strains of cultured mammalian cells with different
      repair capabilities for sublethal damage. NCS enhanced the radiosensitivity of
      the cells when applied both during and after X-irradiation under aerobic
      conditions. The enhancement ratios of NCS during X-irradiation were 1.25, 1.27
      and 1.38 for mouse lymphoma L5178Y, Chinese hamster V79 and mouse mammary tumour
      FM 3A cells, respectively. The corresponding ratios after X-irradiation were
      1.18, 1.27 and 1.38, respectively. These ratios were proportional to the repair
      capabilities of the cells for sublethal damage. NCS completely inhibited the
      repair of sublethal damage regardless of the repair capabilities of the cells for
      sublethal damage. NCS was equally effective for hypoxic cells. These results
      suggested that NCS enhanced the radiosensitivity of the cells probably by
      interacting with the residual damage after X-irradiation, thereby converting the
      sublethal damage or potentially lethal damage into lethal damage.

PMID- 1976723
TI  - Enhancement of radiosensitivity of cultured mammalian cells by neocarzinostatin.
      II. Fixation of potentially lethal damage.
AB  - The effects of neocarzinostatin (NCS), an anti-tumour drug, on the repair of
      potentially lethal damage (PLD) were studied using cultured Chinese hamster V79,
      malignant human melanoma and mouse lymphoma L5178Y cells in the stationary phase.
      The repair of PLD was observed in the melanoma and L5178Y cells but no such
      repair was observed in the V79 cells, when studied by delayed plating. NCS added
      to the culture medium immediately after X-irradiation evoked fixation of PLD
      within 10 min of the addition of NCS. The ratios of D0 values of the survival
      curves of the cells treated with NCS to those plated immediately after X
      irradiation were 0.78, 0.88 and 0.85 for V79, melanoma and L5178Y cells,
      respectively. The extent of the fixation by NCS was similar to that caused by 0.5
      M NaCl solution. The results in the present study and the inhibition of sublethal
      damage (SLD) by NCS reported previously, suggest that NCS might react with the
      DNA damage induced by radiation and modify it to lethal damage. The study
      indicates that SLD and PLD appear to be closely related to one another.

PMID- 1976724
TI  - Protein phosphorylation and kinase activities in tumour cells after hyperthermia.
AB  - Phosphorylation of various proteins and the activities of specific kinases were
      studied in tumour cells after hyperthermia. P388 lymphoid tumour cells were
      treated at 40-45 degrees C for 1 h in vitro. Immediately after heat treatment,
      particulate and cytosol cell fractions were isolated, phosphorylated proteins
      separated and various kinase activities were measured. Hyperthermic treatment of
      the cells caused a significant decrease in protein kinase C activity while the
      activity of calcium-ion and phospholipid-independent protein kinases increased.
      Phosphorylation of cytosol proteins of 120, 80, 33, 25 and 14 kDa increased
      significantly after hyperthermia, and protein kinase C selectively phosphorylated
      the last three of these proteins. The phosphorylation of three heat shock
      proteins (44, 70 and 85 kDa) was not changed after hyperthermic treatment. Four
      tyrosine kinase activities were separated. The protein tyrosine kinase activity
      decreased to one-tenth of the control value after 45 degrees C for 1 h
      hyperthermia. The changes in kinase activities and protein phosphorylation
      induced by hyperthermia proved to be temperature- and time-dependent.

PMID- 1976725
TI  - T-lymphocyte subsets in occupationally exposed persons.
AB  - The percentage of CD2+, CD4+, CD8+ and HNK-1+ cells in peripheral blood was
      investigated in persons occupationally exposed to very low doses of ionizing
      radiation. Investigations were carried out by monoclonal antibodies and flow
      cytometry. While significant effects of age and smoking habits on the relative
      number of CD8 cells and CD4/CD8 ratios could be established, no influence of the
      very low radiation exposure on the profile of lymphocytic T cells in blood was
      found, except a very slight effect on the relative number of CD2+ cells.

PMID- 1976726
TI  - Accelerator mass spectrometry of 36Cl produced by neutrons from the Hiroshima
      bomb.
AB  - Accelerator mass spectrometry was performed at the Munich tandem laboratory to
      determine 36Cl/Cl ratios of samples from a tombstone exposed to neutrons from the
      Hiroshima bomb. The ratios were determined from the surface to deeper positions.
      The depth profile of 36Cl/Cl can be used for estimating the neutron energy
      distribution and intensity near the hypocentre in Hiroshima.

PMID- 1976727
TI  - Fission-neutron-induced expression of a tumour-associated antigen in human cell
      hybrids (HeLa x skin fibroblasts): evidence for increased expression at low dose
      rate.
AB  - The induction of a tumour-associated antigen in a human cell hybrid line (HeLa x
      skin fibroblast) following exposure to fission neutrons of average energy 0.85
      MeV (Janus reactor, Argonne National Laboratory) at two dose rates, 0.086 and
      10.3 cGy/min, has been examined. The dose-response data obtained indicate the
      lower dose rate to be 2.9-fold more effective than the higher in inducing
      expression of the tumour-associated antigen, while there was no significant dose
      rate effect in terms of cell killing. These results are qualitatively in
      agreement with previous observations using neutrons from the Janus reactor for
      the neoplastic transformation of C3H10T1/2 cells and Syrian hamster embryo cells.

PMID- 1976728
TI  - In vitro solubility of uranium tetrafluoride with oxidizing medium compared with
      in vivo solubility in rats.
AB  - A simple in vitro solubility test for uranium tetrafluoride (UF4) was developed
      to investigate the effects of addition of enzymes, proteins or gases such as O2
      to synthetic biological fluid or Gamble solvent. The tests were conducted
      concomitantly with an in vivo inhalation experiment using male rats. In the
      presence of Gamble solvent alone, UF4 exhibited class Y behaviour with a
      dissolution half-time of 300-500 days. However, when oxygen or carbonates were
      added to the Gamble solvent, UF4 displayed class W behaviour, with a half-time of
      25-50 days. Lastly, in the presence of oxygen and pyrogallol, which simulates the
      action of the enzyme NADPH, the superoxide ion (O2-) was formed, which appears to
      have a dominant role in the oxidation of U4+ to U6+. Under these conditions UF4
      behaved like a class D compound, and had a dissolution half-time of only 2-3
      days. These latter results correlated with those of the inhalation experiment in
      which the dissolution half-time was calculated to be between 2.5 and 5.2 days.
      The data are also in agreement with urine monitoring data obtained for workers
      exposed to UF4 over a 20-year period.

PMID- 1976729
TI  - Effect of mass, oxidation state and duration of chronic ingestion on plutonium
      absorption in fed rats.
AB  - The effects of time, mass and oxidation state on plutonium gastrointestinal
      absorption and tooth adsorption were studied during and after chronic ingestion
      of plutonium-238 (IV) or (VI) (1.55-15.60 kBq/ml) in 6.5 mM bicarbonate medium by
      fed rats via drinking water for 8 days to 3 months. Animals were killed during
      the ingestion to follow the kinetics of whole-body storage and clearance of
      plutonium. At 1.55 kBq/ml the amount of plutonium retained in the skeleton
      increased continuously during the 85 days of ingestion and reached a plateau
      thereafter. This plutonium retention was therefore dependent on the total mass
      administered but not proportional to this mass, as the fraction of administered
      plutonium retained decreased during the first 22 days of ingestion and then
      stabilized. This is reflected by the gastrointestinal transfer (f1), which had
      risen to (3.80 +/- 0.82) x 10(-5) on Day 3 of ingestion and then decreased to a
      stabilized value of (1.07 +/- 0.06) x 10(-5) from Day 30 to the end of the
      ingestion period. In the liver, the amount of plutonium retained reached a
      plateau, which lasted from Day 30 to the end of ingestion. The kidneys and spleen
      were also found to be retention sites. By Day 3 of ingestion, for a mass ingested
      of 5 x 10(-7) g/kg of body mass, the maximum mean value of f1 we found was
      smaller than the 10(-4) recommended by ICRP Report 30. The oxidation state had no
      effect on f1. Large plutonium deposition was observed on the teeth. For both
      oxidation states (IV) and (VI), about 0.10% of the administered dose was
      deposited on the teeth after 3 days of ingestion, whatever the plutonium
      concentration administered. However, whereas the amount of plutonium (IV)
      deposited did not change throughout the ingestion period, tooth deposition of
      plutonium (VI) decreased.

PMID- 1976730
TI  - Severe mental retardation after large prenatal exposures to bomb radiation.
      Reduction in oxygen transport to fetal brain: a possible abscopal mechanism.
AB  - Reasonable expectations, based on the normal physiology of the human fetus, cast
      new light on the possibilities of extrapolation from the finding of severe mental
      retardation (SMR) in Japanese bomb survivors after maternal exposure to 1.8-5.5
      Gy T65DR Gy. After such large exposures the fetal haematopoietic tissues (DS86
      dose 0.9-2.2 Gy) cannot escape severe damage and a consequent reduction in
      erythropoiesis. Diminished fetal erythropoiesis will diminish oxygen transport
      from placenta to fetus. Impaired oxygen transport to the developing forebrain
      will augment the localized forebrain damage caused directly by large radiation
      doses. Linear extrapolation of an observed linear dose response for SMR after
      large radiation exposures is unlikely to be a valid method for predicting the
      frequency of SMR after much smaller exposures causing minimal damage to the fetal
      haematopoietic tissues.

PMID- 1976731
TI  - Lack of acute effects of 20 mT, 50 Hz magnetic fields on murine haemopoiesis.
AB  - Some epidemiological studies have drawn attention to a possible association
      between exposure to extremely low-frequency (ELF) electromagnetic fields and the
      development of acute myeloid leukaemia (AML) in adults. At present there is no
      experimental evidence for such an association. We have investigated the acute
      effects of power frequency magnetic fields on haemopoiesis in CBA/H mice known to
      be susceptible to the induction of AML after exposure to ionizing radiation. Up
      to 19 days after exposure to 50 Hz fields at 20 mT for 7 days no significant
      effects on peripheral blood characteristics were observed. Assays of the bone
      marrow stem cells and myelomonocytic progenitor cells also failed to reveal
      significant effects. Our experiments cannot, however, rule out subtle effects on
      cell population dynamics, and further investigations, including long-term
      studies, are required to establish the extent to which ELF magnetic fields might
      affect the haemopoietic system.

PMID- 1976732
TI  - Intestinal endocrine cells in Hirschsprung's disease. No reduction in density in
      aganglionic compared with ganglionic segment.
AB  - The aganglionic intestine in Hirschsprung's disease displays a severe neuronal
      derangement. The changes are particularly evident in the muscular innervation. In
      the gut the endocrine cells are among the cells known to be influenced by
      neurons. We have, therefore, examined the endocrine cells in ganglionic and
      aganglionic intestine using immunocytochemistry and immunochemistry. The
      endocrine cells were studied using antibodies against the neuroendocrine marker
      chromogranin A, the amine serotonin and the hormonal peptides somatostatin,
      glucagon/glicentin and peptide YY (PYY), thus covering virtually all endocrine
      cell types known to occur in this region. The PYY concentration in the mucosal
      layer was measured by radioimmunoassay. In ganglionic as well as in aganglionic
      intestine large populations of cells storing chromogranin A, serotonin, glucagon
      and PYY and a smaller population of somatostatin cells were seen. There was an
      increase in the density of these cells in the aganglionic intestine compared with
      ganglionic. The data indicate that the endocrine cell populations in the
      intestinal wall can be maintained despite severe derangements of the nerve
      supply.

PMID- 1976733
TI  - Molecular basis of polymorphisms of human complement component C3.
AB  - C3 exhibits two common allotypic variants that may be separated by gel
      electrophoresis and are called C3 fast (C3 F) and C3 slow (C3 S). C3 F, the less
      common variant, occurs at appreciable frequencies only in Caucasoid populations
      (gene frequency = 0.20). An increased prevalence of the C3 F allele has been
      reported in patients with partial lipodystrophy, IgA nephropathy, and Indian
      childhood hepatic cirrhosis. Studies of the genomic organization of the human C3
      gene led to the identification of a single change (C to G) between C3 S and C3 F
      at nucleotide 364 in exon 3. This leads, at the translation level, to the
      substitution of an arginine residue (positively charged) in C3 S for a glycine
      residue (neutral) in C3 F. This substitution results in a polymorphic restriction
      site for the enzyme HhaI. The resulting restriction fragment length polymorphism
      (RFLP) was investigated using genomic DNA, amplified using the polymerase chain
      reaction; there was absolute concordance between the genomic polymorphism and the
      distribution of C3 S and C3 F in 50 normal subjects. The molecular basis of a
      second structural polymorphism, defined by the monoclonal antibody HAV 4-1, was
      also characterized. The polymorphic determinant was identified at codon 314 in
      the exon 9 of the beta chain where a leucine residue (HAV 4-1+) is substituted
      for a proline residue (HAV 4-1-). Identification of the amino acid sequences of
      these polymorphic variants will facilitate characterization of possible
      functional differences between different allotypes of C3. Three RFLPs (BamHI,
      EcoRI, and SstI) were located to introns in the C3 gene. There was no allelic
      association between these three RFLPs, or between the RFLPs and the C3 F/S
      polymorphic site. Genetic equilibration of these polymorphisms has occurred
      within a gene of 41 kb.

PMID- 1976734
TI  - Selective anergy of V beta 8+,CD4+ T cells in Staphylococcus enterotoxin B-primed
      mice.
AB  - The cellular basis of the in vitro and in vivo T cell responses to Staphylococcus
      enterotoxin B (SEB) has been investigated. The proliferation and cytotoxicity of
      V beta 8.1,2+,CD4+ and CD8+ T cells were observed in in vitro response to SEB. In
      primary cytotoxicity assays, CD4+ T cells from control spleens were more active
      than their CD8+ counterparts, however, in cells derived from SEB-primed mice,
      CD8+ T cells were dominant in SEB-specific cytotoxicity. In vivo priming with SEB
      abrogated the response of V beta 8.1,2+,CD4+ T cells despite the fact that these
      cells exist in significant number. This SEB-specific anergy occurred only in V
      beta 8.1,2+,CD4+ T cells but not in CD8+ T cells. These findings indicate that
      the requirement for the induction of antigen-specific anergy is different between
      CD4+ and CD8+ T cells in post-thymic tolerance, and the existence of coanergic
      signals for the induction of T cell anergy is suggested.

PMID- 1976735
TI  - Human immunodeficiency virus type 1-infected individuals make autoantibodies that
      bind to CD43 on normal thymic lymphocytes.
AB  - Sera from human immunodeficiency virus type 1 (HIV-1)-infected and -noninfected
      individuals were screened for antibodies that could bind to native T cell
      differentiation antigens. Antibodies that could immunoprecipitate CD43
      (sialophorin, leukosialin) from a T cell lymphoma line were detected in sera from
      27% of patients, and antibodies that could bind specifically to transfected cells
      expressing CD43 were detected in 47% of patients. The anti-CD43 antibodies were
      related to HIV-1 infection in that no patients with other chronic viral
      infections or systemic lupus erythematosus contained such antibodies in their
      sera. The anti-CD43 autoantibodies bound to a partially sialylated form of CD43
      expressed by normal human thymocytes, but not by normal, circulating T
      lymphocytes. However, the determinant(s) recognized by the anti-CD43
      autoantibodies was present on a large proportion of circulating T lymphocytes,
      but masked from antibody recognition by sialic acid residues. These results
      demonstrate that HIV-1 infection is specifically associated with the production
      of autoantibodies that bind to a native T cell surface antigen.

PMID- 1976736
TI  - Dysregulated expression of the T cell cytokine Eta-1 in CD4-8- lymphocytes during
      the development of murine autoimmune disease.
AB  - The development of autoimmune disease in the MRL/MpJ-lpr inbred mouse strain
      depends upon the maturation of a subset of T lymphocytes that may cause sustained
      activation of immunological effector cells such as B cells and macrophages. We
      tested the hypothesis that abnormal effector cell activation reflects
      constitutive overexpression of a T cell cytokine. We found that a newly defined T
      cell cytokine, Eta-1, is expressed at very high levels in T cells from MRL/l mice
      but not normal mouse strains and in a CD4-8- 45R+ T cell clone. The Eta-1 gene
      encodes a secreted protein that binds specifically to macrophages, possibly via a
      cell adhesion receptor, resulting in alterations in the mobility and activation
      state of this cell type (Patarca, R., G. J. Freeman, R. P. Singh, et al. 1989. J.
      Exp. Med. 170:145; Singh, R. P., R. Patarca, J. Schwartz, P. Singh, and H.
      Cantor. 1990. J. Exp. Med. 171:1931). In addition, recent studies have indicated
      that Eta-1 can enhance secretion of IgM and IgG by mixtures of macrophages and B
      cells (Patarca, R., M. A. Lampe, M. V. Iregai, and H. Cantor, manuscript in
      preparation). Dysregulation of Eta-1 expression begins at the onset of autoimmune
      disease and continues throughout the course of this disorder. Maximal levels of
      Eta-1 expression and the development of severe autoimmune disease reflect the
      combined contribution of the lpr gene and MRL background genes.

PMID- 1976737
TI  - VLA-4 mediates CD3-dependent CD4+ T cell activation via the CS1 alternatively
      spliced domain of fibronectin.
AB  - We previously showed that fibronectin (FN) synergized with anti-CD3 in induction
      of CD4+ T cell proliferation, and that VLA-5 acted as a functional FN receptor in
      a serum-free culture system. In the present study, we showed that VLA-4 is also
      involved in this CD3-dependent CD4 cell activation through its interaction with
      the alternatively spliced CS1 domain of FN. When highly purified CD4 cells were
      cultured on plates coated with anti-CD3 plus synthetic CS1 peptide-IgG conjugate,
      significant proliferation could be observed. Neither CS1 alone nor anti-CD3 alone
      induced this activation. This proliferation was completely blocked by anti-VLA
      beta 1 (4B4) and anti-VLA-4 (8F2), while anti-VLA-5 (monoclonal antibody [mAb] 16
      and 2H6) had no effect. These data indicate that VLA-4 mediates CD3-dependent CD4
      cell proliferation via the CS1 domain of FN. Anti-VLA-4 also partially (10-40%)
      inhibited CD4 cell proliferation induced by native FN plus anti-CD3, implying
      that the CS1 domain is active in the native plasma FN. However, this native FN
      dependent proliferation was entirely abolished by addition of anti-VLA-5 alone.
      Moreover, when native FN-coated plates were pretreated with anti-FN (mAb 333),
      which blocks RGDS sites but not CS1 sites, no CD4 cell activation could be
      observed. These results strongly suggest that CD4 cell activation induced by
      plasma FN/anti-CD3 may be dependent on both VLA4/CS1 and VLA5/RGDS interactions,
      although the latter interaction may be required for function of the former.

PMID- 1976738
TI  - Magnitude and kinetics of alterations in plasma catecholamines and leukocyte beta
      adrenergic receptors in response to anaesthesia and surgery.
AB  - We studied the response of the sympatho-adrenal system to varying intensities of
      different stimuli. Concentrations of norepinephrine and epinephrine in plasma as
      well as densities of beta 2-adrenergic receptors on mononuclear leukocytes were
      determined in patients subjected to operations of varying complexity and
      different types of anaesthesia. In patients undergoing hysterectomy (n = 9), the
      maximal increases in plasma norepinephrine and epinephrine were 2.7- and 2.8
      fold, respectively, corresponding to a post-operative decrease of the mononuclear
      leukocyte beta 2-adrenergic receptors of 27% after 4 hours. Patients with
      coronary revascularization (n = 17) were randomly selected to receive either
      enflurane/N2O or neurolept anaesthesia. During intraoperative periods of stress,
      such as cardiopulmonary bypass and hypothermia, norepinephrine and epinephrine
      levels were 2-3 times higher in the neurolept patients, compared with the
      enflurane patients. In the former group, the respective maximal norepinephrine
      and epinephrine concentrations were 9.7 and 28 times the vasal values of the non
      anaesthetized patients. One day postoperatively, the mononuclear leukocyte beta 2
      receptor density decreased maximally by 45 +/- 11% in the enflurane patients, and
      by 53 +/- 6% in the neurolept patients. As early as two to five days after
      cardiac surgery, beta 2-receptor densities were no longer distinguishable from
      the preoperative values. Significant correlations between the increases in
      catecholamine concentrations and the decreases in beta 2-receptor densities did
      not exist. It is concluded that enflurane blocks the sympatho-adrenal response to
      surgical stress more effectively than neurolept anaesthesia.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1976739
TI  - Benzodiazepine abuse and dependence: misconceptions and facts.
AB  - Benzodiazepines can be prescribed for a number of medical conditions. Many
      physicians are reluctant to prescribe benzodiazepines out of fear of producing
      dependence in patients and incurring the disapproval of their peers. Studies of
      psychotropic drug use and abuse demonstrate that individuals using
      benzodiazepines for treatment of a medical illness rarely demonstrate tolerance
      to the therapeutic action of the medication or escalate the dose. Eighty percent
      of benzodiazepines are prescribed for 6 months or less, and elderly women are the
      most common long-term users of low-dose benzodiazepines. In contrast,
      recreational use of benzodiazepines is associated with polysubstance abuse, lack
      of medical supervision, rapid tolerance to the euphoric or sedating side effect,
      and escalation of dose. Most recreational users of benzodiazepines are young men.
      Documentation of indication for use, collection of drug-abuse history, close
      monitoring, and drug holidays can improve the management of this class of
      medication.

PMID- 1976741
TI  - Diagnostic efficacy of a monoclonal antibody-based immunoenzymetric technique for
      quantitation of creatine kinase MB isoenzyme in serum.
AB  - The clinical usefulness of the Tandem-E CK-MB method (A) using two monoclonal
      antibodies to measure the intact cardiac specific creatine kinase isoenzyme (CK
      MB) was evaluated against results obtained by Corning's electrophoretic
      fluorescence scanning method (B) and the DuPont aca mechanized column
      chromatographic method (C). In 95 patients suspected to have myocardial
      infarction, a total of 127 CK's with MB's were simultaneously determined by
      methods "A", "B", and "C". "C" produced a total of 16.5% (21 out of 127) false
      negative or false-positive results. In contrast, CK-MB results obtained by "A"
      correlated very well with those determined by "B" (r = 0.97; N = 64). In
      addition, the clinical course of myocardial infarction as monitored by the
      measurement of CK-MB at various time intervals by both methods showed excellent
      parallelism. Furthermore, "A" was shown to be free of interference from the
      presence of macro CK type I and II. Also, the presence of increasing
      concentrations of CK-BB (up to 29 IU/L) did not alter the assay response of CK-MB
      in these serum samples. In conclusion, we found the Tandem-E CK-MB method to be
      sensitive (sensitivity = 94%) and specific (specificity = 96%).

PMID- 1976740
TI  - Serum immunosuppressive acidic protein levels in blackfoot disease patients and
      cancer patients.
AB  - Immunosuppressive acidic protein (IAP) was first found in the ascitic fluids of
      cancer patients. Its biochemical properties are significantly different from
      those of acidic protein in the serum of normal persons. Previous studies have
      indicated that the serum IAP concentration increases in most cancer patients and
      decreases to a normal level as such patients are cured. Therefore, it has been
      suggested as a useful marker for follow-up in operated cancer patients. In this
      study, analyses and comparisons of serum IAP concentrations have been made among
      53 normal persons in Blackfoot disease endemic areas, 25 patients with diabetes,
      cataracts, hypertension and cardiovascular disease in Blackfoot disease endemic
      areas, 50 breast cancer patients, 13 colorectal cancer patients, and 18 Blackfoot
      disease patients. Serum IAP concentrations were found as follows: 454 +/- 138
      micrograms/ml for normal subjects and 499 +/- 132 micrograms/ml for disease
      patients in Blackfoot disease endemic areas; 520 +/- 149 micrograms/ml for breast
      cancer patients; 864 +/- 341 micrograms/ml for colorectal cancer patients and 950
      +/- 368 micrograms/ml for Blackfoot disease patients. Serum IAP concentrations
      were much higher in Blackfoot disease patients, than in normal persons in
      Blackfoot disease endemic areas (p less than 0.001), and as high as in colorectal
      cancer patients. In Blackfoot disease patients, the mean serum IAP concentration
      of 6 patients coming from the Blackfoot disease endemic areas was as high as
      1,238 +/- 404 micrograms/ml, showing a positive rate of 100% to IAP (i.e. IAP
      concentration exceeds 500 micrograms/ml). We conclude that serum IAP assay of
      Blackfoot disease patients may be useful for prognosis and therapeutic
      monitoring.

PMID- 1976743
TI  - Role of transesophageal echocardiography in detecting left atrial thrombus and
      spontaneous echo contrast in patients with mitral valve disease or non-rheumatic
      atrial fibrillation.
AB  - Instances of left atrial (LA) thrombus and spontaneous echo contrast were
      evaluated by both transthoracic echocardiography (TTE) and subsequent
      transesophageal echocardiography (TEE) in 50 patients with rheumatic mitral
      stenosis (Group I) and 52 patients with non-rheumatic atrial fibrillation (Group
      II). Among these 102 patients, TEE detected LA thrombi in 16 patients (15.7%) and
      spontaneous echo contrast in 35 (34.3%). In contrast, TTE revealed LA thrombi in
      only 8 patients (7.8%) and spontaneous echo contrast in only 2 patients (2.0%).
      All of the LA thrombi and spontaneous echoes detected by TTE were also found by
      TEE. When TEE was applied, patients with spontaneous echo contrast had a
      significantly higher incidence of LA thrombus than did those without this echo
      (42.8% vs 1.5%, p less than 0.01). Spontaneous echo contrast was coexistent in
      all but one of the patients with LA thrombi (15 of 16, 93.7%). In Group I, the
      incidence of spontaneous echo contrast for patients with isolated or predominant
      mitral stenosis was high (68.3%) when TEE was applied, but this echo was not
      observed in any patient who had more than a moderate degree of mitral
      regurgitation. In Group II, 7 patients (13.5%) were also found to have
      spontaneous echo contrast, which could only be detected by TEE. Of these 7
      patients, LA thrombus was noted in 4 by TEE, but only in 1 by TTE. Thus, it can
      be concluded that: (1) TEE is superior to TTE for detecting LA thrombus and
      spontaneous echo contrast; (2) spontaneous echo contrast in LA is not only
      frequently encountered in mitral stenosis without significant mitral
      regurgitation, but is also found in some patients with non-rheumatic atrial
      fibrillation; and (3) the presence of spontaneous echo contrast is associated
      with a higher incidence of LA thrombus and may be considered as a warning sign
      for further formation of LA thrombus.

PMID- 1976742
TI  - A comparison of newly and previously diagnosed diabetics in Taiwan.
AB  - Between 1985 and 1986, during a population survey of diabetes in 1 urban and 5
      rural areas of Taiwan, a total of 11,478 adults aged 40 or older were screened.
      Capillary whole blood glucose was determined with a glucometer (Ames Co.) The
      diabetic criteria followed the WHO designations. From this survey, a comparison
      of 225 newly diagnosed and 383 previously diagnosed diabetics was conducted.
      Multiple regression analysis revealed a highly significant correlation for all
      diabetics with regard to age, body mass index, family history and hypertension,
      but no specific correlation to habitat. Mean fasting glucose levels in previously
      and newly diagnosed diabetics were 172 and 158 (males 158 vs 147 and females 184
      vs 165) mg/dl, respectively, which suggest that treatment is apparently
      inadequate in this population. The prevalent rate (%) of retinopathy for
      previously and newly diagnosed diabetics was 45.2 and 28.3 (males 42.8 vs 33.3
      and females 47.5 vs 24.8), respectively. The prevalence is as common as those
      reported in western countries. In conclusion, previously diagnosed diabetics had
      higher fasting glucose concentrations and prevalent rates of retinopathy than
      newly diagnosed diabetics, and these findings were particularly prominent in
      females.

PMID- 1976744
TI  - Clinical features of rheumatic carditis in adolescents and adults.
AB  - A retrospective study on the clinical features of acute rheumatic fever (RF) with
      carditis in 45 patients, 15 years of age and older (range 15-61), is described.
      Nineteen patients were seen at initial attack; the remaining 26 patients (28
      recurrences) were admitted because of RF recurrence. Of the total 47 episodes,
      carditis was manifested by a significant murmur without previous RF or any known
      rheumatic heart disease in 40%; change in the character of a murmur under
      observation or the appearance of a new murmur in 15%; and acute pericarditis in
      19%. Congestive heart failure of recent onset was noted in 85% of the episodes,
      while classical polyarthritis or polyarthralgia occurred in 57%. The aortic valve
      was newly damaged or preexisting aortic regurgitation worsened in 12 episodes.
      Twenty-nine patients were followed for 1/2-16 years. Of 11 patients with an
      initial attack who were maintained on regular prophylaxis (intramuscular
      benzathine penicillin 1,200,000 units every 4 weeks), the mitral valve murmur
      disappeared in 3 and none of the patients had recurrence. Of the remaining 18
      patients with no or incomplete prophylaxis, 1 died from congestive heart failure
      6 months later, and 3 had recurrences with involvement of the aortic valve. In
      conclusion, RF with carditis in adolescents and adults in our practice at the
      National Taiwan University Hospital is likely to show more cardiac problems and
      complications than that seen in the West. Although active rheumatic carditis
      among this patient population is relatively uncommon, recurrences with subsequent
      involvement of the aortic valve (aortic regurgitation) do occur.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1976745
TI  - Ultrasonic evaluation of cervical lymphadenopathy.
AB  - Seventy-seven patients with various underlying diseases underwent real-time
      ultrasonographic study of the neck. The sonography of lymph nodes can be round or
      ovoid shaped, discrete hypoechoic nodules, or multiple confluent lobulated
      heterogeneous or homogeneous hypoechoic masses. Venous invasion by a malignant
      lymph node can also be demonstrated by ultrasonography as a loss of echogenicity
      in the vessel wall. Twenty-five patients with malignant cervical lymph nodes
      showed homogeneous discrete hypoechoic nodules. Eleven patients with malignant
      lymph nodes showed a multiple confluent lobulated hypoechoic picture, among them,
      2 patients also had discrete hypoechoic nodules. Eight patients with multiple
      confluent lymph nodes showed evidence of venous invasion. Among 42 patients with
      a clinically palpable neck mass, 1 showed venous thrombosis in the internal
      jugular vein, 2 had abscesses, and 3 had normal musculo-skeletal tissues. Among
      35 patients with clinically impalpable cervical lymph nodes, 5 patients had
      cervical lymphadenopathy. All 41 patients with sonographically detectable lymph
      nodes underwent aspiration cytology or biopsy, and 36 of these showed malignancy,
      4 TB lymphadenitis and 1 nonspecific inflammation. No complication was observed
      in this series. We conclude that ultrasonography is a valuable tool to evaluate
      cervical lymphadenopathy and to clarify the histopathological features of the
      affected lymph nodes with the aid of aspiration cytology.

PMID- 1976746
TI  - Detection of human papillomavirus (HPV) DNA in laryngeal papilloma.
AB  - Laryngeal papillomas are troublesome benign tumors of the larynx. According to
      their biological behavior, there are two types of laryngeal papillomas--the
      juvenile and adult types. Two samples of adult-type and five samples of juvenile
      type laryngeal papilloma specimens were studied using the Southern blot technique
      with radioactively labeled human papillomavirus (HPV) 6b, 16, 18 deoxyribonucleic
      acid (DNA) as probes. We found that there was a linear form, an episomal form,
      and a concatemer or catenane of HPV DNA in the 5 samples of juvenile laryngeal
      papilloma and there was no evidence of HPV DNA integration. The HPV DNA in tumor
      cells is very closely associated with HPV 6b, but has no positive hybridization
      with HPV 16 and 18 DNA even in a low stringent condition. There was no positive
      hybridization found in the 2 samples of adult-type laryngeal papilloma with any
      of the three probes.

PMID- 1976747
TI  - Histologic reactions to a newly developed calcium phosphate cement implanted in
      the periapical and periodontal tissues.
AB  - A newly developed calcium phosphate cement (CPC), basically composed of
      tetracalcium phosphate, Ca4(PO4)2O and dicalcium phosphate dihydrate, CaHPO4.2H2O
      or anhydrous calcium phosphate, CaHPO4, was tested in this study. When combined
      with water, the cement hardens and produces hydroxylapatite resembling the
      principal mineral of teeth and bones. Therefore, the CPC should be highly
      compatible with the body. However, before its clinical application in dentistry,
      the biocompatibility of CPC in the potential environments of implantation needs
      confirmation. Eight monkeys were used in our study to test the material in the
      periapical and marginal periodontal regions. Surgically created periodontal
      defects were implanted with CPC and hydroxylapatite (HA) (Calcitite 4060). In
      another application, CPC was pushed into the periapical areas via overfilling of
      the root canals. Sargenti N2 served as the control material in the periapical
      test. Generally, only a limited inflammatory response to CPC was found after 6
      weeks of implantation in the periodontal area. In the 16-week specimens, the
      adverse reaction was negligible, and bone regeneration was marked and directly
      surrounding the CPC. The bone formation activity and biocompatibility in general
      were found to be even better in the periapical region. The results suggest that
      the CPC may have a good potential in future clinical applications, although many
      issues remain to be investigated.

PMID- 1976748
TI  - Accuracy and consistency of drop delivery in infusion pumps.
AB  - Advances in intensive care medicine has made us more depend on infusion pumps to
      deliver accurate amounts of fluids to sick newborns, children and adults. When
      infusing rapid-acting critical drugs to patients, it is important not only to
      deliver accurate fluid-volume amounts over a specified time, but also to deliver
      the fluid at a constant rate with minimal fluctuation. The accuracy of drop
      delivery in four infusion pumps (IVAC 530, IVAC 560, IMED 922 and IMED 960) at
      different infusion rates were examined in a laboratory setting by using a
      photoelectric sensor and a computer. When it was not in its cassette-filling
      period, the IMED 960 was the most accurate at delivering fluid-drops, with a
      coefficient of variance (CV) of less than 10% at each flow rate. Yet, like other
      piston-cylinder cassette pumps, its cassette filling time and stabilizing period
      after cassette filling were longer at lower flow rates. Both the IVAC 530 and the
      IMED 922 delivered fluids irregularly with large coefficients of variance (CVs).
      IVAC 560 had the best results for consistency of drop-delivery over a 4-hour
      period.

PMID- 1976749
TI  - Idiopathic hypothalamic hypogonadism with polyostotic fibrous dysplasia: report
      of a case.
AB  - A 48-year-old man with Albright's syndrome and hypogonadism is presented.
      Eunuchoid status, hypogenitalia and hypogonadotropinemia were associated with
      pathological fracture and deformity of bones. GnRH test revealed minimal LH
      response and delayed FSH peak. After pulsatile GnRH priming, the LH response to
      GnRH increased. Results of other provocative hypothalamic-pituitary tests were
      consistent with hypothalamic lesions. To the best of our knowledge, this is the
      first report of a male patient with Albright's syndrome and idiopathic
      hypothalamic hypogonadism. The hypothesis of endocrinopathy and its relation to
      other components of this syndrome were reviewed.

PMID- 1976751
TI  - [Experimental hip dysplasia in the rabbit].
AB  - Neglected cases of congenital dislocation of the hip (CDH) always present with
      profoundly interesting X rays and pathoanatomical changes. Because of progressive
      dysplastic change, it is difficult to determine clinically at what stage a
      patient can not have reconstructive surgery. We used an animal model to induce
      hip dysplasia in order to understand the mechanism of dislocation and to
      demonstrate the dysplastic changes at various ages of dislocation. We used a
      plastic tube to immobilize the left knee of one week old New Zealand white
      rabbits in the extension position. Fifty-five rabbits in a natural history group
      were examined physically, radiographically and pathologically every month, until
      five months old. Ten rabbits were also studied by computed tomography before
      sacrifice. Forty-two rabbits which had been immobilized for more than 2 months
      were selected to determine the changes in their left hips. Tenotomy of the
      hamstrings of the left knee was performed in another 20 rabbits, which were then
      immobilized in the same way until 2 months old. The changes in their left hips
      were also determined and compared with the changes of former group. In our study,
      immobilization of the left knee of rabbits can induce dislocation, subluxation or
      no change. Tenotomy of the hamstrings can decrease the incidence of dislocation
      and subluxation, but cannot avoid their occurrence. In long-term observation of
      rabbits with dislocation and subluxation, we found that there are more dysplastic
      and degenerative changes in older rabbits. Computed tomography proved to be an
      effective evaluation tool of the size of dysplastic acetabulum and femoral head.

PMID- 1976750
TI  - Non-surgical radical treatment of early gastric cancer by endoscopic contact Nd
      YAG laser: report of a case.
AB  - A case of flat-elevated type (IIa) early gastric cancer completely eradicated
      with contact Nd-YAG laser is reported. The patient was diagnosed as having early
      gastric cancer (type IIa) by endoscopic examination. Biopsy revealed a well
      differentiated adenocarcinoma. He declined surgery and subsequently received 4
      sessions of contact Nd-YAG laser treatment with a total output of 1245 watt-sec.
      An ulceration was created by the end of the third session of laser treatment. He
      finally agreed to surgery and a subtotal gastrectomy was performed after
      completion of four sessions of therapy. Meticulous histologic examination of the
      resected specimens revealed no residual cancer cells. This is the first report of
      endoscopic curative treatment of gastric cancer by contact Nd-YAG laser in
      Taiwan. This technique may provide an alternative for patients with early gastric
      cancer, who have a high surgical risk.

PMID- 1976752
TI  - [The occurrence and clinical significance of antibodies to type II collagen in
      sera and synovial fluid of Chinese patients with rheumatoid arthritis].
AB  - Antibodies to type II collagen (Col II) in sera and synovial fluid (SF) were
      measured with an enzyme linked immunosorbent assay (ELISA) using a solid phase
      sandwich method. The subjects included: 42 patients with rheumatoid arthritis
      (RA); 31 cases of osteoarthritis (OA); 10 cases of gouty arthritis; 4 cases of
      ankylosing spondylitis (AS); 5 cases of systemic lupus erythematosus (SLE); and
      44 normal controls. The antigens used to detect antibodies against Col II were in
      native and heat-treated denatured forms, both of which were purified from chicken
      sternal cartilage by limited enzyme digestion and differential precipitation with
      salt. The reactivity to native type II collagen was generally higher than the
      reaction to the denatured collagen. In sera, significant higher levels of Col II
      were detected in the different arthritis groups when compared with the normal
      control group, with the exception of AS. In SF, the Col II was significantly
      higher in RA than it was in OA (p less than 0.001), while no difference was
      present between gout and OA (p less than 0.05). When native Col II was
      simultaneously measured in sera and SF among arthritics, positive rates were both
      higher among RA (65% and 58%, respectively). Positive rates were only higher in
      sera among OA (59% in sera and 3% in SF) and were both lower among gouty
      arthritis. The above findings show that the measurement of Col II is more
      important in SF than in sera.

PMID- 1976753
TI  - Solubilization of spermidine-sensitive (+)-[3H]5-methyl-10,11-dihydro-5H
      dibenzo[a,d]cyclohepten-5,10-imine ([3H]MK-801) binding activity from rat brain.
AB  - The receptor-ionophore complex of the N-methyl-D-aspartate (NMDA)-sensitive
      receptor was solubilized by deoxycholic acid from rat brain using (+)-[3H]5
      methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imi ne ([3H]MK-801) binding
      as a marker for the receptor. Gel filtration of the solubilized preparations on a
      Sephadex G-25 column revealed significant [3H]MK-801 binding sensitive to
      potentiation by glutamate and glutamate/glycine, which was prevented by
      competitive antagonists for the NMDA and strychnine-insensitive glycine (GlyB)
      sites. In contrast to NMDA and glycine, spermidine markedly potentiated the
      amount of [3H]MK-801 binding in solubilized preparations by increasing the
      apparent affinity of the ligand. In the presence of all three stimulants, the
      solubilized preparations exhibited pharmacological profiles similar to those in
      the membrane preparations. These results clearly indicate that the whole
      macromolecular NMDA receptor-ionophore complex is solubilized under the
      experimental conditions used.

PMID- 1976754
TI  - Evidence that somatostatin enhances endogenous acetylcholine release in the rat
      hippocampus.
AB  - The present experiments show that somatostatin (SS)-like immunoreactive material
      is present in the hippocampus and that its release can be increased by K+
      stimulation of rat hippocampal slices, suggesting that SS-like peptides may be of
      significance to neurotransmission in the hippocampus. Exogenous SS-28 and SS-14
      enhanced the K(+)-evoked release of endogenous acetylcholine (ACh) from rat
      hippocampal slices, whereas amino-terminal fragments of SS-28 did not. The
      increased ACh release in the presence of either peptide appeared to be mediated
      by an interaction with SS receptors because cyclo-SS, a putative SS antagonist,
      abolished the effects of both SS-28 and SS-14. In addition, the increase in ACh
      release induced by SS-14 or SS-28 was antagonized by the calcium channel
      antagonists omega-conotoxin GVIA, nifedipine, and cinnarizine, implicating
      voltage-sensitive calcium channels in this effect. Moreover, the effect was
      sensitive to tetrodotoxin, suggesting an indirect action of the peptides at a
      site distal to cholinergic nerve terminals. Cysteamine, which has been reported
      to deplete SS content and to increase SS release in brain, augmented the basal
      and evoked release of ACh from hippocampal slices, without affecting SS-like
      content and release. Finally, neuropeptide Y, which is colocalized with SS in
      many neurons of the hippocampal formation, did not alter ACh release, nor did it
      facilitate the SS-induced increase. The results suggest that in the rat
      hippocampus, both SS-28 and SS-14 interact with SS receptors to regulate ACh
      release indirectly by a mechanism that involves alterations of calcium influx
      during depolarization.

PMID- 1976755
TI  - Maitotoxin induces phosphoinositide turnover and modulates glutamatergic and
      muscarinic cholinergic receptor function in cultured cerebellar neurons.
AB  - Maitotoxin (MTX) stimulated inositol phosphate (IP) formation in primary cultures
      of rat cerebellar granule cells. MTX-induced IP production was dependent on
      extracellular Ca2+ but independent of extracellular Na+. The stimulation of IP
      formation elicited by MTX was unaffected by pretreatment of cells with phorbol
      dibutyrate, pertussis toxin, and a variety of Ca2+ entry blockers, such as
      nimodipine, nisoldipine, Co2+, and Mn2+. The presence of MTX markedly attenuated
      IP production induced by carbachol and glutamate, with no apparent effect on the
      responses to norepinephrine (NE), histamine, 5-hydroxytryptamine (5-HT), and
      endothelin-1. The inhibition of the carbachol- and glutamate-induced responses by
      MTX was dose dependent with IC50 values of 1.2 and 0.5 ng/ml, respectively.
      Pretreatment of cells with a lower concentration of MTX (0.3 ng/ml) also
      attenuated carbachol- and glutamate-induced IP formation, in a time-dependent
      manner, with a decrease observed after 30 min prestimulation, but failed to
      affect NE-, histamine-, 5-HT-, endothelin-1, and sarafotoxin S6b-induced
      responses. Thus, MTX elicited a marked Ca2(+)-dependent phosphoinositide (PI)
      turnover in cerebellar granule cells and selectively inhibited carbachol- and
      glutamate-induced PI hydrolysis. Possible mechanisms underlying these selective
      modulations are discussed.

PMID- 1976756
TI  - Lysosulfatide (sulfogalactosylsphingosine) accumulation in tissues from patients
      with metachromatic leukodystrophy.
AB  - We describe here a sensitive assay method for lysosulfatide
      (sulfogalactosylsphingosine) in human tissues using HPLC. The method involves
      extraction of lipids, saponification, isolation using a C18 Sep-Pak column,
      derivatization with o-phthalaldehyde, and detection of the fluorescent
      lysosulfatide using HPLC. In control subjects, a small amount of lysosulfatide
      was detected in the cerebral white matter (9-35 pmol/mg of protein), spinal cord
      (35 pmol/mg of protein), sciatic nerve (14 pmol/mg of protein), and kidney
      (approximately 2 pmol/mg of protein) but not in the cerebral gray matter and
      liver. A marked accumulation of the lipid was noted in tissues from six patients
      with metachromatic leukodystrophy (MLD). The concentration of lysosulfatide was
      high in the cerebral white matter, spinal cord, and sciatic nerve (223-1,172
      pmol/mg of protein). Even in the cerebral gray matter, kidney, and liver, where
      lysosulfatide was hardly detected in the control sample, a considerable amount (3
      45 pmol/mg of protein) accumulated in MLD patients. The concentration and
      distribution pattern of lysosulfatide were similar to those of
      galactosylsphingosine (psychosine) accumulated in patients with Krabbe disease.
      Therefore, the accumulation of lysosulfatide may explain the demyelination in
      patients with MLD, as is the case with Krabbe disease.

PMID- 1976757
TI  - 5-Hydroxytryptamine amplifies beta-adrenergic stimulation of N-acetyltransferase
      activity in rat pinealocytes.
AB  - In cultured rat pinealocytes beta-adrenergic induction of N-acetyltransferase, a
      key enzyme in the synthesis of melatonin, is amplified by addition of 5
      hydroxytryptamine (5-HT) to the culture medium. However, 5-HT when added alone
      has no effect on enzyme activity. Pharmacological experiments with a range of
      agonists and antagonists suggest that this action is not mediated by 5-HT1, 5
      HT2, 5-HT3, or 5-HT4 receptor subtypes but may involve a site similar to the 5
      HT1p receptor described in the enteric nervous system. The potential role of 5-HT
      in modulating adrenergic stimulation of N-acetyltransferase activity is
      discussed.

PMID- 1976758
TI  - Glutamate-stimulated, guanine nucleotide-mediated phosphoinositide turnover in
      astrocytes is inhibited by cyclic AMP.
AB  - The potential for cross-talk between the adenyl cyclase and phosphoinositide
      (PPI) lipid second messenger system was investigated in astrocytes cultured from
      neonatal rat brain. Glutamate-stimulated PPI turnover, measured by the formation
      of total inositol phosphates from myo-[3H]inositol-labeled lipids, was inhibited
      in a concentration-dependent manner by the elevation of intracellular cyclic AMP
      levels produced either by stimulation of the isoproterenol receptor linked to
      adenyl cyclase or by its direct activation by forskolin. N6,2'-O-Dibutyryl cyclic
      AMP, an analogue that can also activate cyclic AMP-dependent kinase, inhibited
      glutamate-stimulated PPI turnover in a concentration-dependent manner as well, a
      result suggesting that cyclic AMP-dependent kinase is involved in mediating the
      inhibition. Inclusion of an inhibitor of cyclic AMP-dependent kinase, 1-(5
      isoquinolinesulfonyl)-2 methylpiperazine dihydrochloride or N-(2-guanidinoethyl)
      5-isoquinolinesulfonamide hydrochloride, blocked the cyclic AMP-mediated
      inhibition in a concentration-dependent manner, a finding further supporting this
      hypothesis. The site of inhibition of the phosphoinositol lipid pathway by cyclic
      AMP was probed using a digitonin-permeabilized cell system. Guanosine 5'-O-(3
      thiotriphosphate), a nonhydrolyzable analogue of GTP, stimulated PPI turnover and
      potentiated glutamate-stimulated PPI turnover, and guanosine 5'-O-(3
      thiodiphosphate) inhibited glutamate-stimulated PPI turnover in these cells,
      results providing evidence that glutamate receptors are coupled to phospholipase
      C by a guanine nucleotide binding protein in astrocytes.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1976759
TI  - The effects of opioid peptides on dopamine release in the nucleus accumbens: an
      in vivo microdialysis study.
AB  - An involvement of the mesolimbic dopamine (DA) system in mediating the
      motivational effects of opioids has been suggested. Accordingly, the present
      study employed the technique of in vivo microdialysis to examine the effects of
      selective mu-, delta-, and kappa- opioids on DA release in the nucleus accumbens
      (NAC) of anesthetized rats. Microdialysis probes were inserted into the NAC and
      perfusates were analyzed for DA and its metabolites, dihydroxyphenylacetic acid
      (DO-PAC) and homovanillic acid (HVA), using a reverse-phase HPLC system with
      electrochemical detection for separation and quantification.
      Intracerebroventricular (i.c.v.) administration of selective mu-opioid [D-Ala2, N
      methyl-Phe4, Gly5-ol]-enkephalin (DAMGO) or delta-opioid [D-Pen2, D-Pen5]
      enkephalin (DPDPE) agonists, at doses that function as positive reinforcers in
      rats, resulted in an immediate and significant increase in extracellular DA.
      DOPAC and HVA levels were also significantly increased. The effects of DAMGO were
      blocked by the selective mu-antagonist D-Pen-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2
      (CTOP) whereas those of DPDPE were blocked by the delta-antagonist allyl2-Tyr-Aib
      Aib-Phe-Leu-OH (ICI 174,864). In contrast to mu- and delta-agonists, the kappa
      agonist N-CH3-Tyr-Gly-Gly-Phe-Leu-Arg-N-CH3-Arg-D-Leu-NHC2H5 (E-2078), a
      dynorphin analog that produces aversive states, decreased DA release in a
      biphasic manner. Norbinaltorphimine, a selective kappa-antagonist, could block
      this effect. These results demonstrate that mu-, delta-, and kappa-opioid
      agonists differentially affect DA release in the NAC and this action is centrally
      mediated.

PMID- 1976760
TI  - Tyrosine hydroxylase mRNA concentration in midbrain dopaminergic neurons is
      differentially regulated by reserpine.
AB  - Tyrosine hydroxylase (TH)-mRNA, assayed by in situ hybridization combined with TH
      immunocytochemistry, showed a selective increase in the ventral tegmental area (A
      10) but not in the substantia nigra (A-9) midbrain dopaminergic (DAergic) neurons
      3 days after reserpine treatment. TH-mRNA in locus ceruleus noradrenergic (A-4)
      neurons was increased by reserpine, as confirmed by RNA blot hybridization. These
      findings show that TH-mRNA is differentially regulated in midbrain DAergic
      neurons in response to reserpine.

PMID- 1976762
TI  - Novel glutamate receptor antagonists selectively protect against kainic acid
      neurotoxicity in cultured cerebral cortex neurons.
AB  - The effect on excitatory amino acid (EAA)-induced toxicity of two novel non-N
      methyl-D-aspartate (non-NMDA) antagonists 2-amino-3-[3-(carboxymethoxy)-5
      methylisoxazol-4-yl]propionic acid (AMOA) and 2-amino-3-[2-(3-hydroxy-5-methyl
      isoxazol-4-yl)methyl-5-methyl-3- oxoisoxazolin-4-yl]propionic acid (AMNH) was
      tested in primary cultures of cerebral cortex neurons. Such cultures provide a
      useful model for the investigation of the toxicity of EAAs and a convenient
      screening system for potential neuroprotective activity of pharmacological
      agents. It was demonstrated that AMNH and AMOA abolished neurotoxicity induced by
      kainic acid with IC50 values of 62 +/- 10 and 120 +/- 19 microM, respectively. No
      effect on neuronal damage induced by NMDA or AMPA could be detected.

PMID- 1976761
TI  - Serotonin stimulates both cytosolic and membrane-bound guanylate cyclase in NG108
      15 cells.
AB  - The cyclic GMP (cGMP) content was rapidly (greater than 30 s) increased by
      serotonin [5-hydroxytryptamine (5-HT)] (EC50 = 10 microM), and the increase
      lasted for greater than 10 min in NG108-15 cells. The 5-HT-induced elevation of
      cGMP level (EC50 = 10 microM) at 20 s ("fast" elevation) was inhibited by ICS 205
      930 or MDL 72,222 and by Ca2+ deficiency in the reaction medium but not by
      organic Ca2+ antagonists. The 5-HT effect at 10 min ("slow" elevation) was not
      inhibited by several antagonists for 5-HT receptors of the 1A, 1B, 1C, 1D, 2, and
      3 subtypes and was independent from external Ca2+ concentration. The fast and
      slow effects of 5-HT were similar to the effects of bradykinin and atrial
      natriuretic peptide (ANP), respectively, in aspects of both Ca2+ dependency and
      time course of the effects. Bradykinin transiently stimulated formation of
      inositol phosphates as well as accumulation of cGMP, a finding suggesting that
      intracellular Ca2+ is involved in bradykinin-induced cGMP accumulation as shown
      in the fast response to 5-HT. ANP, an activator of membrane-associated guanylate
      cyclase (mGC), slowly (approximately 60 s) increased the cGMP content (EC50 = 10
      nM), a result lasting for greater than 10 min, and the effects were independent
      from external Ca2+, as shown in the slow response to 5-HT. 5-HT and ANP did not
      induce formation of inositol phosphates.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1976764
TI  - VII International Congress on Neuromuscular Diseases. 16-22 September 1990,
      Munich, Federal Republic of Germany. Abstracts.

PMID- 1976763
TI  - Low plasma iron status and akathisia.
AB  - Thirty patients were examined to test the hypothesis that a depletion of iron
      levels is associated with symptoms of akathisia. Fifteen akathisic patients were
      pair-matched with 15 non-akathisic patients. Plasma ferritin levels were
      significantly decreased in the akathisic patients, and there was a significant
      inverse correlation between plasma iron levels and akathisia rating. In addition,
      akathisia ratings were found to be correlated with a scale measuring symptoms of
      tardive dyskinesia.

PMID- 1976766
TI  - Excitatory synaptic transmission in cultures of rat olfactory bulb.
AB  - 1. Olfactory bulb neurons were dissociated from neonatal rats and plated at low
      density on a confluent layer of olfactory bulb astrocytes. Intracellular
      stimulation of presumptive mitral/tufted (M/T) cells evoked monosynaptic
      excitatory postsynaptic potentials (EPSPs) in adjacent neurons. Whole-cell
      recording techniques and a flow-pipe drug delivery system were used to compare
      EPSPs with voltage-clamp recordings of currents evoked by excitatory amino acids
      (EAA) including N-acetylaspartylglutamate (NAAG), a putative mitral cell
      transmitter. 2. Cultured olfactory bulb neurons were morphologically and
      physiologically distinct. Large pyramidal-shaped neurons were present, which were
      NAAG immunoreactive; stimulation of these neurons invariably evoked EPSPs,
      suggesting that they were M/T cells. The majority of small bipolar neurons were
      glutamic acid decarboxylase (GAD) immunoreactive consistent with granule or
      periglomerular gamma-aminobutyric acid (GABA)ergic interneurons. 3. Monosynaptic
      EPSPs between M/T cells could be separated into fast and slow components by the
      use of EAA receptor antagonists. A fast component with a time-to-peak of 7.7 +/-
      1.0 (SE) ms and half-width of 31.8 +/- 7.4 ms was blocked by the non-NMDA
      receptor antagonist 6-cyano-2,3-dihydroxy-7-nitro-quinoxaline (CNQX, 2.5 microM).
      The slow component (time-to-peak = 41.4 +/- 7.2 ms; half-width = 218.9 +/- 40.4
      ms) was blocked by the N-methyl-D-aspartate (NMDA) receptor antagonist DL-2-amino
      5-phosphonovaleric acid (AP5, 100 microM). 4. Under voltage clamp, flow-pipe
      applications of NAAG (10-1,000 microM) evoked inward currents at a holding
      potential of -60 mV in Mg-free solutions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1976765
TI  - Excitatory amino acid-mediated transmission of inspiratory drive to phrenic
      motoneurons.
AB  - 1. The role of excitatory amino acids (EAAs) in the bulbospinal transmission of
      inspiratory drive was studied by intracellular and single-electrode voltage-clamp
      recordings from phrenic motoneurons in the in vitro neonatal rat brain stem
      spinal cord. 2. In all brain stem-spinal cord preparations there were
      spontaneously generated rhythmic membrane depolarizations and associated spiking
      of phrenic motoneurons during the inspiratory phase of the respiratory cycle. The
      envelope of the motoneuron drive potential had a rapid onset to peak (50 ms)
      followed by a plateau/declining phase that lasted 400-700 ms. The peak potential
      was approximately 10-20 mV above base-line potential. The drive current under
      voltage clamp had a similar shape and duration to the drive potential with a peak
      current greater than 1.5 nA. 3. The involvement of EAAs in the bulbospinal
      transmission of inspiratory drive was demonstrated by checking the effects of
      various EAA receptor antagonists on the phrenic motoneuron inspiratory drive.
      When kynurenic acid (KYN), an antagonist acting on all three subtypes of EAA
      receptors, was applied to the solution bathing the spinal cord, the motoneuron
      action potentials were abolished, and the amplitude of inspiratory drive
      potential was significantly reduced. To further classify the role of the
      different EAA receptor subtypes in the synaptic transmission of inspiratory
      drive, the effects on the drive potential of either 6-cyano-7-nitroquinoxaline
      2,3-dione (CNQX), a specific non-N-methyl-D-aspartic acid (non-NMDA) receptor
      antagonist, or DL-2-amino-5-phosphonovaleric acid (AP5), DL-2-amino-7
      phosphonoheptanoic acid (AP7), and (+)-5-methyl-10,11-dihydro-5H
      dibenzo[a,d]cyclohepten-5,10-imin emaleate (MK-801), NMDA receptor antagonists,
      were investigated. Bath or local application of CNQX induced a dose-dependent
      decrease of the inspiratory drive potential without changing intrinsic motoneuron
      membrane properties. On the other hand, application of AP7 or MK 801 had a small
      effect on the inspiratory drive potential or the inspiratory drive current when
      the motoneuron membrane potential was clamped near end-expiratory potentials (-60
      to -75 mV). 4. To establish the presence of EAA receptors on the phrenic
      motoneuronal membrane and to provide information on the available receptor
      subtypes for action of the endogenously released transmitter, we tested the
      effects of agonists for the major EAA receptor subtypes after blocking synaptic
      transmission (produced by axonal action potentials) by bath application of
      tetrodotoxin (TTX).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1976767
TI  - Expression of neuropeptide-Y-like immunoreactivity begins after adrenergic
      differentiation and ganglionic synaptogenesis in developing bullfrog sympathetic
      neurons.
AB  - Immunoreactivities for tyrosine hydroxylase (TH) and neuropeptide Y (NPY) were
      studied in developing sympathetic neurons of bullfrog tadpoles and adults. At
      stage III, nearly all ganglion cells are positive for TH. This suggests early
      commitment to an adrenergic phenotype, the timing of which is analogous to that
      reported for sympathetic neurons in birds and mammals. During metamorphic stages
      and in juvenile bullfrogs, the expression of TH becomes transiently bimodal: many
      neurons are intensely positive; the remainder are faintly positive. In adult
      sympathetic neurons, TH expression is more uniform. NPY first appears in a few
      principal neurons (less than 1%) of paravertebral ganglia 9 and 10 at stage XI.
      The percentage of ganglion cells containing NPY then increases gradually, reaches
      adult levels (approximately 55%) by stage XX, and persists at these levels
      through metamorphosis. The development of NPY expression follows a similar time
      course in paravertebral ganglion 6. Double-label experiments in late-stage
      tadpoles and juvenile bullfrogs revealed that the intensely TH-positive neurons
      are negative for NPY. Taken together with recent electrophysiological data (Horn
      and Stofer, 1990), these results demonstrate that the development of NPY
      expression begins long after the onset of adrenergic differentiation and
      ganglionic synapse formation. The present findings also show that cellular levels
      of TH and NPY can be independently altered, and they suggest that the onset of
      NPY expression is not linked to maturation of peripheral targets, but rather to
      some more global event operating synchronously along the rostro-caudal axis.

PMID- 1976769
TI  - Early unilateral deprivation modifies olfactory bulb function.
AB  - Unilateral olfactory deprivation during postnatal development produces
      significant structural and neurochemical modifications of the olfactory bulb. In
      the present report, we describe the functional consequences of such deprivation.
      Rat pups had a single naris occluded on postnatal day 2 (PN2) to deprive them of
      early olfactory stimulation. On PN20-22, the occluded naris was reopened, the
      previously open naris was sealed, and responses of the deprived olfactory bulb to
      odors were assessed using both single-unit recording from mitral/tufted cells and
      quantitative 14C-2-deoxyglucose (2-DG) autoradiography. While the response
      properties of individual odor-stimulated mitral/tufted cells were not altered by
      early deprivation, spontaneous activity was depressed, and there was a
      significantly higher incidence of odor-responsive mitral/tufted cells in deprived
      compared to nondeprived bulbs. In addition, odor-stimulated deprived bulbs
      demonstrated greater uptake of 2-DG than did non-deprived bulbs. Together, these
      data indicate that the olfactory system demonstrates an increased responsiveness
      to sensory cues following early deprivation.

PMID- 1976768
TI  - Neuropeptide cotransmitters released from an identified cholinergic motor neuron
      modulate neuromuscular efficacy in Aplysia.
AB  - Intrinsic buccal muscle 5 (I5) in Aplysia is innervated by 2 motor neurons
      (termed B15 and B16). In addition to the classical transmitter ACh, B15 also
      contains the 2 neuropeptides SCPA and SCPB. In a previous study, we demonstrated
      that the SCPs were released from the terminals of B15 in the I5 muscle and that
      this release was sufficient to raise cAMP levels in I5 muscle fibers. Significant
      peptide release occurred only when B15 was stimulated at high frequency or at
      lower frequencies with a relatively long burst duration (Whim and Lloyd, 1989).
      In the present article, we examine the possibility that the SCPs released from
      B15 modulate I5 muscle contractions produced by stimulation of the second motor
      neuron, B16. Application of exogenous SCPs to I5 muscles increased the amplitude
      and relaxation rate of B16-evoked contractions. Stimulation of B15 using
      paradigms that have been shown previously to cause release of the SCPs resulted
      in a long-lasting increase in the amplitude and relaxation rate of muscle
      contractions evoked by B16. This modulation is unlikely to be due to the B15
      induced muscle contractions themselves, because modulation of B16-evoked
      contraction amplitude and relaxation rate was observed when the contractions were
      blocked transiently by a cholinergic antagonist during B15 stimulation.
      Conversely, stimulation of B15 at frequencies that produce no measurable release
      of the SCPs did not elicit significant modulation of B16-evoked contractions. The
      minimum B15 stimulation frequency required to elevate muscle cAMP levels or to
      modulate B16-evoked contractions was found to be within the physiological range
      at which B15 fires during feeding. Therefore, the mechanism underlying the
      modulation of B16-evoked contractions by B15 is likely to involve the release of
      the SCPs from B15 terminals in the I5 muscle. With respect to behavior, this
      modulation of muscle contractions would be most likely to occur during food
      induced arousal when both motor neurons fire at high frequency with brief
      interburst intervals.

PMID- 1976770
TI  - XXIV national congress of the Italian Society for Nuclear Biology and Medicine
      (SIBMN) in conjunction with the X meeting of the "Autonomous Nuclear Medicine
      Section of the Italian Radiology Association (SAMN-SIRMN)" Lido di Venezia
      (Italy) October 10 through 13, 1990. Abstracts.

PMID- 1976771
TI  - Antihypertensive medications: relative effectiveness and adverse reactions.
AB  - Thiazide diuretics may be more effective as antihypertensive agents in many
      subsets of patients than other medications, especially in reducing systolic blood
      pressure. Angiotensin converting enzyme (ACE) inhibitors and beta-blockers are
      less effective than calcium blockers or diuretics in black hypertensives and beta
      blockers may be less effective in the elderly. Calcium blockers are equally
      effective in blacks, whites and the elderly but may not be as efficacious as
      diuretics. When used as initial monotherapy, most available antihypertensive
      drugs produce significant adverse subjective effects in about 8-10% of patients;
      centrally acting drugs, however, may produce annoying side effects in 20-30% of
      patients. Usually, some medication can be found that lowers blood pressure and is
      acceptable to the patient. Adverse metabolic effects are probably of limited long
      term clinical significance except in a few patients. An approach to therapy that
      will prove effective in a majority of patients is outlined. Any one of the four
      classes of agents may appropriately be used as initial monotherapy (diuretics,
      beta-blockers, ACE inhibitors, calcium blockers). Diuretics are recommended as
      the second drug of choice if one of the other agents is used first. With this
      approach approximately 80% or more of patients can be controlled at normotensive
      levels on one or at most two drugs.

PMID- 1976772
TI  - Evaluation of children with multiple endocrine neoplasia type IIb following
      thyroidectomy.
AB  - Medullary thyroid carcinoma (MTC) develops in all patients with multiple
      endocrine neoplasia type IIb (MEN IIb), a rare syndrome that either occurs
      sporadically or is inherited in an autosomal dominant pattern. The MTC in
      patients with MEN IIb has been reported to be biologically aggressive with onset
      at a young age and rapid progression as evidenced by widespread metastases and
      death, frequently in the teenage years. Seven children, aged 2 to 11 years (mean,
      7 years), from three kindreds with MEN IIb were evaluated for evidence of tumor
      recurrence 3 to 10 years following thyroidectomy. In one child, age 11, a thyroid
      mass was palpable preoperatively. However, in the remaining six children (aged 2
      to 10 years), the diagnosis of MTC was established by an increased concentration
      of plasma calcitonin (CT), either basally or following pentagastrin (Pg)
      stimulation. All patients underwent total thyroidectomy with removal of central
      lymph nodes from the neck. At the time of surgery, six children were found to
      have bilateral macroscopic MTC, five without and one with cervical metastases.
      One child (age 2 years) had C-cell hyperplasia, a premalignant precursor of MTC.
      Currently, five of the seven children are without evidence of recurrent disease
      clinically and have normal plasma CT levels (less than 0.3 ng/mL) following
      calcium (Ca) and Pg stimulation 3, 3, 10, 10, and 10 years after thyroidectomy.
      Two of the seven children have biochemical evidence of residual MTC.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1976773
TI  - Does the distal rectal muscle in anorectal malformations have the functional
      properties of a sphincter?
AB  - Smooth muscle strips from the distal rectum of 11 patients who underwent surgery
      for imperforate anus and cloacal malformations, were studied in vitro to assess
      the motility response to electrical field stimulations (EFS) and to
      pharmacological stimulation with adrenergic and cholinergic agonists. EFS induced
      a nonadrenergic, noncholinergic inhibition in most strips. Acetylcholine caused
      either a modest contraction, no response, or a relaxation. Following atropine
      administration, acetylcholine caused a nonadrenergic and tetrodotoxin-resistant
      relaxation. The alpha-adrenergic agonist phenylephrine induced contractions in
      all strips. The response was abolished by alpha-adrenoceptor blockade with
      phentolamine, but was resistant to atropine and tetrodotoxin. beta-Adrenergic
      stimulation caused a relaxation that was abolished by propranolol. Function of
      the distal rectal smooth muscle, resected during correction of anorectal
      malformations, shows similarities to the function reported previously on normal
      anal smooth muscle evaluated in vitro.

PMID- 1976774
TI  - The retention of entrapped molecules within erythrocyte ghosts during
      cryopreservation.
AB  - In view of the interest in erythrocyte ghosts and carrier erythrocytes as
      potential drug delivery systems, this work was undertaken to determine conditions
      facilitating the retention of entrapped molecules during cryopreservation. Upon
      freeze-thaw treatment intact erythrocytes and erythrocyte ghosts displayed
      different damage profiles with respect to cryoprotectant concentration. Non
      penetrating cryoprotectants showed optimum protection of intact cells at 0.4-0.5
      M; this optimum was not observed with ghosts, in which damage decreased with
      concentration up to 1.0 M. The concentration optimum for intact cells was not
      abolished by oxidative or reductive treatments suggesting that its absence in
      ghosts is not due to altered protein-protein or protein-lipid interactions. The
      extent of freeze-thaw damage to ghosts was influenced by the qualitative ionic
      composition of a cryoprotectant-free suspending medium, with 10-12% haemolysis
      observed in the presence of Li+ and Mg2+ but greater than 60% for Na+, Cs+, K+
      and NH4+ with increasing loss following that order. The release on freezing of
      entrapped haemoglobin, insulin and sucrose was found to be inversely proportional
      to their molecular weights.

PMID- 1976775
TI  - Inhibition of dapsone-induced methaemoglobinaemia in the rat isolated perfused
      liver.
AB  - We have investigated the disposition of dapsone (DDS, 1 mg) in the rat isolated
      perfused liver in the absence and the presence of cimetidine (3 mg). After the
      addition of DDS alone to the liver there was a monoexponential decline of parent
      drug concentrations and rapid formation of DDS-NOH (within 10 min) which
      coincided with methaemoglobin formation (11.7 +/- 3.0%, mean +/- s.d.) which
      reached a maximum (22.6 +/- 9.2%) at 1 h. The appearance of monoacetyl DDS
      (MADDS) was not apparent until 30-45 min. Addition of cimetidine resulted in
      major changes in the pharmacokinetics of DDS and its metabolites. The AUC of DDS
      in the presence of cimetidine (1018.8 +/- 267.8 micrograms min mL-1) was almost
      three-fold higher than control (345.0 +/- 68.1 micrograms min mL-1, P less than
      0.01). The half-life of DDS was also prolonged by cimetidine compared with
      control (117.0 +/- 48.2 min vs 51.2 +/- 22.9, P less than 0.05). The clearance of
      DDS (3.0 +/- 0.55 mL min-1) was greatly reduced in the presence of cimetidine
      (1.03 +/- 0.26 mL min-1 P less than 0.01). The AUC0-3h for DDS-NOH (28.3 +/- 21.2
      micrograms min mL-1) was significantly reduced by cimetidine (8.1 +/- 3.40
      micrograms min mL-1, P less than 0.01). In contrast, there was a marked increase
      in the AUC0-3h for MADDS (32.7 +/- 25.8 micrograms min mL-1) in the presence of
      cimetidine (166.0 +/- 26.5 micrograms min mL-1 P less than 0.01). The
      methaemoglobinaemia associated with DDS was reduced to below 5% by cimetidine.
      Hence, a shift in hepatic metabolism from bioactivation (N-hydroxylation) to
      detoxication (N-acetylation) caused by cimetidine, was associated with a fall in
      methaemoglobinaemia. These data suggest that the combination of DDS with a
      cytochrome P450 inhibitor might reduce the risk to benefit ratio of DDS.

PMID- 1976776
TI  - Correlation between structures of organic cations and their binding behaviours to
      brush border membrane isolated from rat small intestine.
AB  - We have investigated the correlation between the molecular structures of various
      organic cations and their binding to rat small intestinal brush border membrane.
      The binding of small quaternary ammonium compounds such as tetramethylammonium
      and choline to brush border membrane was not sufficient to inhibit
      methylchlorpromazine binding. However, lauryltrimethylammonium and
      cetyltrimethylammonium, both quaternary amines with a long carbon chain,
      inhibited binding significantly. The inhibition was competitive. When the
      unbranched hydrocarbon chain of the quaternary amines was extended in steps from
      C1 (methyl) to C16 (cetyl), the inhibitory effect increased sharply with length
      from C7 (heptyl) to C16. These results suggest that the size of the hydrophobic
      part of the molecule is an important factor in binding of quaternary ammonium
      compounds to the brush border membrane. The structure of the hydrophilic part was
      another factor. In imipramine-related compounds, the order of binding was N
      didesmethylimipramine (primary amine) greater than desipramine (secondary)
      greater than imipramine (tertiary) greater than methylimipramine (quaternary).
      However, with the small molecular ethylamine-related compounds, binding
      properties did not reflect differences in the hydrophilic component. Therefore,
      the effect of the hydrophilic part may be secondary and may depend on the size of
      the hydrophobic part. We suggest that organic cations which are amphiphilic can
      bind to a common binding site on brush border membrane through hydrophobic and/or
      hydrophilic interactions.

PMID- 1976777
TI  - Contribution of passive transport mechanisms to the intestinal absorption of beta
      lactam antibiotics.
AB  - The transport characteristics of aminopenicillins (ampicillin and amoxicillin),
      aminocephalosporins (cephalexin, cephradine and cefadroxil) and cefazolin have
      been compared with those of an actively transported substance (D-glucose) and a
      passively transported substance (L-glucose). Although the initial uptake of the
      aminocephalosporins was stimulated in the presence of an inward H+ gradient,
      there was no overshoot in the uptake of any of the drugs tested, even in the
      presence of an H+ gradient. Also, the time course and the degree of uptake of
      these drugs were similar to those of L-glucose, especially in the absence of an
      H+ gradient. These results suggest that the beta-lactam antibiotics tested, like
      L-glucose, pass through the rat intestinal brush border membrane mainly by
      passive diffusion. However, the differences in absorption between these drugs,
      like the differences in their disappearance from a proximal loop of rat
      intestine, cannot be explained by a simple permeation process alone.

PMID- 1976778
TI  - The effects of (+/-)-, (+)- and (-)-celiprolol and bromoacetylalprenololmentane
      at the beta-adrenoceptors of rat isolated cardiovascular preparations.
AB  - The effects of (+/-)-, (+)- and (-)-celiprolol and of
      bromoacetylalprenololmentane (BAAM, an irreversible beta-adrenoceptor antagonist)
      on the contractile responses of the electrically driven rat right ventricle strip
      to isoprenaline and on the relaxant responses of the rat aorta to procaterol,
      have been studied. Racemic and (-)-celiprolol or BAAM treatment of the ventricle
      produced non-parallel rightward shifts of the isoprenaline response curves with a
      reduction in the maximal response. Sotalol produced parallel rightward
      displacements of the procaterol response curves of the aorta with no effect on
      the maximal relaxations. Racemic and (+)- and (-)-celiprolol or BAAM treatment of
      the aorta produced non-parallel rightwards shifts of the procaterol relaxant
      curves with a reduction in the maximal relaxation. The BAAM data was used to
      demonstrate that the KA (dissociation constant) for isoprenaline at beta 1
      adrenoceptors was 1.46 x 10(-7) M and for procaterol at beta 2-adrenoceptors was
      2.34 x 10(-5) M. Calculation of receptor occupancy demonstrated that to produce a
      maximal response of the rat right ventricle, had to occupy 87% of the beta 1
      adrenoceptors. Likewise, for a maximal response of the rat aorta, procaterol had
      to occupy 81% of the beta 2-adrenoceptors. It is suggested that the use of
      tissues with small beta-adrenoceptor reserves has shown that (+/-)- and (-)
      celiprolol are slowly dissociating, rather than readily reversible, beta
      adrenoceptor antagonists.

PMID- 1976779
TI  - Effects of verapamil, nifedipine and flunarizine on haemodynamics and regional
      blood flows in pentobarbitone-anaesthetized rats.
AB  - Representative calcium antagonists from proposed class I (nifedipine), class II
      (verapamil) and class III (flunarizine) have been examined for effects on blood
      pressure, heart rate, ventricular pressures, ECG, cardiac output and regional
      blood flow in pentobarbitone-anaesthetized rats. Flow was measured by the
      microsphere technique. Low and high infusion rates of each drug were chosen to
      decrease mean arterial pressure by 25 and 40 mmHg, respectively. At equi
      depressor infusion rates, all drugs equally decreased total peripheral resistance
      and slightly increased cardiac output and stroke volume. Heart rate was decreased
      by verapamil and flunarizine, but increased by nifedipine. Verapamil markedly
      decreased dP/dtmax of ventricular pressure and prolonged the PR-interval.
      Flunarizine was similar. Nifedipine decreased dP/dtmax and had no effect on the
      PR-interval of the ECG. Similar effects on regional blood flow were seen with the
      three drugs; flow to lungs, heart, liver, skeletal muscle and stomach increased.
      Correction for blood pressure changes, i.e. conductance, showed that
      vasodilatation occurred in all regions, with all drugs, except for the skin.
      Therefore, representatives from three sub-classes of calcium antagonists had
      similar effects on blood flow but different effects on the heart.

PMID- 1976780
TI  - Further studies on the metabolism of methylamine by semicarbazide-sensitive amine
      oxidase activities in human plasma, umbilical artery and rat aorta.
AB  - An ion exchange radiochemical assay has been developed to study the deamination
      of [14C]methylamine (MA) in homogenates of rat aorta and human umbilical artery,
      as well as in samples of human plasma. MA metabolism was found to be inhibited
      almost completely by 1 mM semicarbazide, but virtually unaffected by 0.1 mM
      clorgyline, suggesting that MA is a substrate for the semicarbazide-sensitive
      amino oxidase (SSAO) activities which also metabolize benzylamine (BZ) in these
      sources. Mean Km values for MA metabolism by aorta, umbilical artery and plasma
      were 182, 832 and 516 microM, respectively, with corresponding Vmax values in
      aorta and umbilical artery of 100 and 590 nmol (mg prot.)-1 h-1, and in plasma of
      48 nmol (mL serum)-1 h-1. Kinetic constants determined for [14C]BZ metabolism in
      plasma (by an organic solvent extraction assay) and in umbilical artery (by the
      ion exchange assay) yielded mean Km values of 225 microM (plasma), 222 microM
      (umbilical artery), and Vmax values of 28 nmol (mL serum)-1 h-1 (plasma) and 377
      nmol (mg prot.)-1 h-1 (umbilical artery). The deamination of [14C]MA was
      inhibited competitively by unlabelled BZ, with Ki values in umbilical artery and
      plasma of 220 and 172 microM, respectively. Also, metabolite formation from
      mixtures of [14C]BZ (200 microM) and [14C]MA (800 microM) was extremely close to
      that predicted for a single enzyme capable of metabolizing two alternative
      substrates in a competitive fashion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1976781
TI  - Effect of pinacidil on the electrophysiological properties in guinea-pig
      papillary muscle and rabbit sino-atrial node.
AB  - The electrophysiological effect of the antihypertensive drug pinacidil has been
      examined in preparations of guinea-pig papillary muscle and rabbit sino-atrial
      node using a standard microelectrode method. In papillary muscle preparations,
      pinacidil (greater than 30 microM) shortened the action potential duration (APD),
      whereas it did not affect the maximum rate of rise (Vmax). Pinacidil (greater
      than 1 microM) also decreased APD of slow action potentials evoked by high K+ (27
      mM) solution containing 0.2 mM Ba2+. At 30 microM, the drug reduced the Vmax of
      slow action potentials. In the spontaneously beating sino-atrial node, pinacidil
      (greater than 30 microM) shortened APD. At 100 microM, it also decreased the
      heart rate, Vmax, action potential amplitude and the rate of diastolic
      depolarization. It is concluded that pinacidil modifies the electrical activity
      of myocardial cells probably due to an increase in the potassium conductance
      although in high concentrations the compound might also reduce Ca2+ influx
      through the cell membrane, which would contribute to an obvious negative
      chronotropic action.

PMID- 1976782
TI  - Comparison of propranolol and sotalol pharmacokinetics in obese subjects.
AB  - Six obese subjects (mean +/- s.d. : 145.1 +/- 16.7% of ideal body weight) were
      randomly assigned to a single i.v. dose either of (+/-)-propranolol base (0.108
      mg kg-1 of ideal body weight) or of (+/-)-sotalol base (1.06 mg kg-1 of ideal
      body weight). Each subject received the other drug 7 days later. Pharmacokinetic
      parameters were compared with those obtained previously in non-obese control
      subjects. In obese subjects, the pharmacokinetic data calculated for sotalol were
      comparable with those measured in controls (total body clearance = 9.4 +/- 2.9 L
      h-1; volume of distribution during the terminal phase = 79.8 +/- 19.8 L or 0.9 +/
      0.2 L kg-1; terminal half-life = 6.2 +/- 1.6 h). For propranolol, total
      clearance (44.3 +/- 15.9 L h-1) and volume of distribution (230.5 +/- 48.2 L or
      2.7 +/- 0.7 L kg-1) were significantly less than control values. The terminal
      half-life (3.9 +/- 1.1 h), was not significantly increased. These results could
      be explained by altered tissue blood flow and a decreased metabolic capacity of
      the liver in obese subjects.

PMID- 1976783
TI  - A pattern recognition study of acyclic ureide anticonvulsants.
AB  - A pattern recognition structure-activity study employing topological, geometric
      and physicochemical descriptors was performed on 27 acyclic ureide
      anticonvulsants. Twelve numerical descriptors were used as variables in a
      discriminant function analysis which categorized the ureide analogues with
      respect to their bioactivity. The results from the discriminant function analysis
      were interpreted to support a model for antiepileptic activity.

PMID- 1976784
TI  - The effect of an antacid and food on the absorption of cimetidine and ranitidine.
AB  - The effect of varying doses of a liquid antacid preparation containing magnesium
      hydroxide, aluminum hydroxide and simethicone on the absorption of the H2
      receptor antagonists, cimetidine and ranitidine, was determined in 2 groups of 11
      volunteers; one group fasted and one group fed a standardized breakfast. The
      antacid alone caused a significant decrease in the AUC of cimetidine (24%).
      Similarly, concomitant antacid caused a 59% decrease in the AUC of ranitidine.
      There were no effects on any of the other pharmacokinetic parameters examined.
      The absorption of both drugs was similar in fasted and fed volunteers, but in the
      fed volunteers the antacid did not produce the decrease in AUC seen in the fasted
      volunteers. These data suggest that H2-receptor antagonists should not be taken
      at the same time as antacids.

PMID- 1976785
TI  - Chronic administration of MK-801 and the NMDA receptor: further evidence for
      reduced sensitivity of the primary acceptor site from studies with the cortical
      wedge preparation.
AB  - Cortical slices removed from rats pre-treated with MK-901 0.5 mg kg-1 twice a day
      for 7 days had reduced responses to N-methyl-D-aspartate (NMDA) relative to
      quisqualate and glutamate compared with control animals. Potencies of competitive
      (CPMP) and non-competitive (ketamine) NMDA antagonists appeared unchanged. These
      changes are consistent with a reduced density of NMDA receptors.

PMID- 1976786
TI  - Stereoselective hydrolysis of O-acetyl propranolol as prodrug in human serum.
AB  - A direct high-performance liquid chromatographic method was developed for the
      assays of the enantiomers of O-acetyl propranolol. Using this procedure, the
      stereochemical characteristics on hydrolysis of racemic O-acetyl propranolol as a
      prodrug have been studied in phosphate buffer (pH 7.4) and in 90% human serum. In
      the phosphate buffer, no difference in the hydrolysis rate between the esters of
      (R)- and (S)-propranolol was observed. In 90% human serum, the hydrolysis of the
      esters was accelerated, and the hydrolysis rate of the ester of (R)-isomer was
      about three times faster than that of the ester of (S)-isomer. The
      interconversion between (R)- and (S)-isomer was not observed during the
      hydrolysis of prodrug in buffer and in human serum. These results indicated that
      hydrolysis of O-acetyl propranolol occurs stereoselectively in human serum.

PMID- 1976788
TI  - Suppression of ventricular arrhythmias resulting from acute coronary artery
      ligation in rat by imipramine.
AB  - The potential antiarrhythmic activity of imipramine against ventricular
      arrhythmias induced by coronary artery ligation in rats has been investigated and
      compared with procainamide. Imipramide (1 and 5 mg/kg-1) or procainamide (5 and
      10 mg/kg-1) or solvent were injected intravenously 30 min before ligation.
      Imipramine reduced the total number of ventricular ectopic beats as well as the
      incidence and duration of ventricular tachycardia and ventricular fibrillation.
      The drug did not significantly affect the blood pressure but reduced the heart
      rate. The antiarrhythmic activity of imipramine is postulated to be due to a
      quinidine-like effect and/or alpha-adrenergic blocking activity. The study
      confirms the potential utility of imipramine as an antiarrhythmic drug.

PMID- 1976787
TI  - The selectivity of the opioid antagonist, naltrindole, for delta-opioid
      receptors.
AB  - In the mouse vas deferens, naltrindole gave pKB values of 9.7, 8.3, and 7.5 at
      the delta-, mu-, and kappa-sites and in binding assays, pIC50 values of 9.6, 7.8
      and 7.2 at the same sites. The affinity of naltrindole for the delta binding site
      was increased in the presence of sodium ions and 5'-guanylylimidophosphate.
      Naltrindole is, thus, a potent opioid antagonist with marked selectivity for the
      delta-opioid receptor.

PMID- 1976790
TI  - The effect of loperamide oxide on prostaglandin-stimulated fluid transport in rat
      small intestine.
AB  - The effects of loperamide and loperamide oxide on basal and prostaglandin E2
      stimulated fluid transport by rat small intestine have been investigated. In
      contrast to loperamide, loperamide oxide, when applied intraperitoneally, failed
      to inhibit either basal or prostaglandin E2-stimulated fluid transport. However,
      intraperitoneal administration of loperamide oxide following its incubation with
      the contents of the intestinal lumen under aerobic conditions resulted in an
      effective inhibition of fluid secretion. The activating material was present in
      the essentially non-particulate 3000 g supernatant fraction of the luminal
      contents and was heat-stable.

PMID- 1976789
TI  - In-vivo and in-vitro hepatoprotective effect of 4-thia-prostaglandin E1 and 7
      fluoroprostacyclin in rats.

PMID- 1976791
TI  - Potencies of mioflazine and its derivatives as inhibitors of adenosine transport
      in isolated erythrocytes from different species.
AB  - The potency of mioflazine and related drugs (Janssen Pharmaceutica, Belgium) as
      inhibitors of adenosine transport in isolated erythrocytes from several species
      were measured and compared with those of dilazep and 6-(4
      nitrobenzylmercapto)purine ribonucleoside (NBMPR). [8-3H]Adenosine was used as
      the permeant at 1 microM and incubation times were 10 s, and assays were
      conducted in the presence and absence of varying doses of potential transport
      inhibitors. The species investigated included mouse, hamster, rabbit, baboon and
      man. Dilazep was the most potent compound throughout with an IC50 of about 2 nM.
      In the mouse and hamster mioflazine and its derivatives were considerably less
      potent (IC50 values greater than 200 nM) with the exception of R57974 with IC50
      values of about 150 and 60 nM in mouse and hamster, respectively. In the man and
      baboon the derivatives had IC50 values in the same order of magnitude as NBMPR
      (less than 100 nM), and in the rabbit they had potencies close to that of NBMPR,
      ranging between 10-60 nM. Nucleoside transport inhibitors are of potential
      importance as host protectors during treatment of parasitic infections with
      cytotoxic nucleosides. Present data indicate that mioflazine and its derivatives
      are not very potent in some of the preferred animal models for parasitic
      infections (mouse, hamster) but are more effective in primates such as man and
      baboon.

PMID- 1976792
TI  - Endothelin action on goat cerebral arteries.
AB  - Cumulative application of endothelin-1 (human) markedly constricted goat isolated
      cerebral arteries in a concentration-dependent manner. Contractile responses were
      not affected by removal of endothelial cells. Removal of extracellular calcium or
      addition of the calcium channel blocker nicardipine (10(-7) M) failed to abolish
      responses to endothelin. The results suggest that the endothelium-independent
      constriction of cerebral arteries produced by endothelin cannot be explained
      solely by voltage-dependent calcium channels. The contractile responses are
      likely to be mediated by stimulation of specific receptors for this peptide.

PMID- 1976793
TI  - Kynurenic acid blocks chemogenic nociception.
AB  - Previous studies have suggested a role of excitatory amino acids (EAA) in
      nociception. In the present study the effects of two antagonists of EAA-receptors
      on capsaicin-induced eye wipings were investigated. Intracisternally administered
      kynurenic acid, in contrast to intravenously administered MK-801, was found to
      effectively block the induced eye wipings. It is proposed that EAA, by activating
      non-NMDA receptors, are involved in the transmission of chemogenic nociception.

PMID- 1976794
TI  - The effects of raubasine and dihydroergocristine on an age-related deficit in
      passive avoidance learning in rats.

PMID- 1976795
TI  - On the use of laboratory markers as surrogates for clinical endpoints in the
      evaluation of treatment for HIV infection.
AB  - There are strong ethical and practical reasons for hastening decision-making
      about the efficacy of new treatments for human immunodeficiency virus (HIV)
      infection. One strategy is to use early markers of disease progression, such as
      CD4+ lymphocyte levels, as surrogates for ultimate clinical endpoints, such as
      the development of acquired immune deficiency syndrome (AIDS) or death, in the
      evaluation of new therapies. We used a simple model of transitions among three
      health states (well; alive but with an adverse marker; and having experienced a
      definitive clinical endpoint) to examine the extent to which treatment
      comparisons based on the surrogate endpoint predict ultimate clinical benefits.
      With parameters chosen to model the treatment of HIV infection, computer
      simulations of clinical trials demonstrated substantial time savings by use of
      the surrogate endpoint. However, reliance on the surrogate led to serious
      overestimates of ultimate clinical benefit if treatment entailed delayed toxicity
      or had only transient beneficial effects. Likewise, reliance on the surrogate led
      to serious underestimates of ultimate clinical benefit when the treatment had no
      effect on the transition from well to the marker state but did reduce the rates
      of transition from the marker state to the ultimate clinical endpoint and
      directly from the well state to the ultimate clinical endpoint.

PMID- 1976796
TI  - ["T" lymphocytes. Their role in periodontal disease].
AB  - The immune response is now proved to be of great importance in the control of
      periodontal diseases. The predominant role of T lymphocytes in the mechanisms of
      specific immunity is admitted and is related to the functions of effectors T
      cells and T-helper cells, controlling the response of macrophages and the
      antibody production. The relations between the evolution of the disease and the
      tissular T/B and T4/T8 ratio and the lymphocyte function tests are discussed.

PMID- 1976797
TI  - Serotonin induces constriction and relaxation of the guinea pig airway.
AB  - The response of guinea pig trachea to 5-hydroxytryptamine (serotonin; 5-HT) was
      investigated by studying tracheal strips suspended in organ chambers for
      isometric tension measurements. Serotonin concentrations of 0.1 to 10 microM
      produced concentration-dependent contractions, whereas at higher concentrations
      (10-300 microM) the agonist caused concentration-dependent relaxations. The 5-HT2
      antagonist ketanserin shifted the bimodal 5-HT response-curve to the right (pA2
      for ketanserin was 8.98). The 5-HT1A agonist, (+)-8-hydroxy-2-(di-N
      propylamino)tetralin hydrobromide and 5-HT3 antagonist, ICS 205930 (3-tropanyl
      indole-3-carboxylate) had no effect on the 5-HT-response curve. Incubation with
      atropine resulted in a depression of the maximal contractility and an increase in
      the EC50 without changing the bimodal nature of the concentration-response curve.
      Hexamethonium was able to block the atropine effect without significantly
      affecting the 5-HT concentration-response curve. Neither the constriction nor the
      relaxation was altered by propranolol, chlorpheniramine or capsaicin
      pretreatment. Histamine and carbachol preconstricted airways were also relaxed by
      5-HT in a concentration-dependent fashion and this relaxation was antagonized by
      ketanserin (pKb for ketanserin in histamine preconstricted airways was 9.4).
      Epithelial denudation did not inhibit the 5-HT-induced relaxation. 5-HT
      stimulated inositol-monophosphate production which also exhibited a bimodal
      response and correlated well with the functional response. The above findings
      suggest that 5-HT causes both constriction and relaxation of the guinea pig
      airway, and that both responses are antagonized by a 5-HT2 receptor blocker. In
      addition, part of the constrictor response of 5-HT is mediated through a
      cholinergic preganglionic pathway. Finally, inositol-monophosphate production
      induced by 5-HT correlates with the functional response.

PMID- 1976798
TI  - A beta adrenoceptor with atypical characteristics is involved in the relaxation
      of the rat small intestine.
AB  - In several studies in guinea pig ileum or rat colon a beta adrenoceptor with
      characteristics distinct from beta-1 or beta-2 receptors has been observed and
      has been denoted as "atypical" beta adrenoceptor. In this study the relaxation of
      the rat small intestine was investigated, using isolated segments of the rat
      jejunum. Several beta-1 or beta-2 agonists and antagonists were tested on the rat
      jejunum preparation, and it was found that nonselective and selective antagonists
      for beta-1 or beta-2 receptors showed a relatively low affinity, compared to
      their affinity for beta-1 or beta-2 receptors. BRL 37344, an agonist which has
      been reported to be selective for the atypical beta adrenoceptor, was more potent
      although a partial agonist compared to isoprenaline, whereas it is clearly less
      active than isoprenaline on beta-1 or beta-2 receptors. These findings indicate
      that beta adrenergic relaxation of the rat small intestine is mediated via
      atypical beta adrenoceptors. Efforts were made to confirm these findings with
      binding studies on small intestinal 45,000-g membranes. Competition radioligand
      binding experiments were performed with the radiolabeled ligand
      [125I]iodocyanopindolol and the various antagonists which were also tested in the
      intact rat jejunum preparations. Receptor binding experiments only revealed beta
      adrenoceptors of the beta-2-subtype, which does not correspond with the results
      obtained in the jejunum relaxation. Probably the beta-2 receptors found in the
      binding studies are located on circular smooth muscle cells or on epithelial
      cells, whereas longitudinal smooth relaxation is mediated by atypical beta
      adrenoceptors. Atypical beta adrenoceptors were not measured in binding studies
      probably because [125I]iodocyanopindolol is an unsuitable ligand to label
      atypical intestinal beta adrenoceptors.

PMID- 1976799
TI  - Role of vasopressin in response to intrarenal infusions of alpha-2 adrenoceptor
      agonists.
AB  - Previous studies have indicated that the effects of renal alpha-2 adrenoceptor
      stimulation are mediated through the blockade of the renal effects of
      vasopressin. If this premise is correct then 1) specific antagonists of the
      antidiuretic effect of vasopressin (V2 antagonists) should mimic alpha-2
      adrenoceptor stimulation and 2) in the presence of V2 antagonists, the diuretic
      and natriuretic effect of clonidine should be attenuated. The renal effects of
      [d(CH2)5,D-Ile2,Ile4]AVP, a specific V2 antagonist, were studied. On the day of
      the experiment, uninephrectomized rats were anesthetized, and the carotid artery
      and jugular vein were cannulated for recording blood pressure and saline
      infusion, respectively. The left kidney was exposed and the ureter cannulated. A
      31-gauge needle was advanced into the renal artery to permit direct i.r. infusion
      of study drugs. Bolus doses of the V2 antagonist (0, 1, 3, 10, or 30 nmol/kg
      i.v.) produced a dose-related increase in urine volume and free water clearance
      at all doses tested. Sodium excretion increased only at the higher doses (10 and
      30 nmol/kg). This dose-related dissociation in water and then sodium excretion is
      similar to that observed after i.r. clonidine infusions. In the presence of the
      V2 antagonist, clonidine (3 micrograms/kg/min) had no effect on urine volume or
      free water clearance but significantly decreased the excretion of sodium from
      control. These results demonstrate that V2 antagonists mimic the effects of i.r.
      clonidine. As well, in the absence of vasopressin (V2 antagonism), the effects of
      clonidine are attenuated. Moreover, they are also consistent with not only an
      antidiuretic role for endogenous vasopressin but also an antinatriuretic one.

PMID- 1976800
TI  - Effects of (+)-4-propyl-9-hydroxynaphthoxazine on midbrain dopamine neurons: an
      electrophysiological study.
AB  - (+)-4-Propyl-9-hydroxynaphthoxazine (PHNO) is a highly potent, D2-selective
      dopamine (DA) receptor agonist. In the present study, we have examined the
      electrophysiological effects of PHNO on identified nigrostriatal DA (NSDA),
      mesoaccumbens DA (MADA) and Type I caudate neurons. Intravenous PHNO dose
      dependently inhibited the firing rate of NSDA and MADA neurons in both chloral
      hydrate (CH)-anesthetized rats (ED50 values = 21.2 +/- 1.2 and 26.5 +/- 1.4
      ng/kg, respectively) and locally anesthetized, paralyzed rats (ED50 values =
      105.0 +/- 1.4 and 109.1 +/- 1.4 ng/kg, respectively). PHNO was significantly more
      potent in the CH-anesthetized rats. There was a significant, positive correlation
      between basal firing rate and log ED50 for NSDA neurons in both preparations and
      for MADA cells only in CH-anesthetized animals. Neither pretreatment with the D1
      receptor agonist SKF 38393 nor hemitransection of the forebrain altered the rate
      dependent nature of PHNO-induced inhibition of NSDA neurons. Likewise, depletions
      of serotonin with either p-chlorophenylalanine or 5,7-dihydroxytryptamine failed
      to alter the rate-dependent PHNO-induced inhibition of NSDA neurons.
      Iontophoretically applied PHNO inhibited both NSDA and MADA neurons to a similar
      degree as either DA or the D2 agonist quinpirole. In contrast, the similar
      effects of PHNO and quinpirole on Type I caudate neurons were significantly
      different than those of DA. These results suggest that PHNO inhibits midbrain DA
      neurons via stimulation of somatodendritic autoreceptors and that PHNO exhibits
      an electrophysiological profile characteristic of D2 agonists. In contrast to
      quinpirole, however, the rate-dependent nature of PHNO-induced inhibition of
      these cells was resistant to modulation.

PMID- 1976801
TI  - Tachykinin gene expression in rat limbic nuclei: modulation by dopamine
      antagonists.
AB  - The content and nature of the preprotachykinin (PPT; i.e., substance P/neurokinin
      A-encoding) messenger RNAs (mRNAs) present in rat brain striatum and limbic
      tissues were determined by RNA protection experiments. The rank order of PPT mRNA
      concentration was striatum greater than nucleus accumbens much greater than bed
      nucleus of the stria terminalis greater than hypothalamus, amygdala and septum.
      The proportion of beta-(full length) to gamma-(minus exon 4) PPT mRNA was
      invariant (40/60) among the tissues tested. Because these brain regions receive
      prominent dopaminergic innervations, the effects of repeated treatment with
      dopamine antagonists (antipsychotic drugs) on PPT gene expression were assessed.
      The prototypical dopamine antagonists haloperidol and chlorpromazine decreased
      striatal PPT mRNA, had no effect on PPT mRNA in the nucleus accumbens or bed
      nucleus of the stria terminalis, and increased septal PPT mRNA levels. In
      contrast, the atypical antipsychotic drugs clozapine and l-sulpiride did not
      alter striatal or septal PPT mRNA, but increased PPT mRNA content in the nucleus
      accumbens and bed nucleus. The correlation between the effects of typical and
      atypical antipsychotic drugs on rat striatal and limbic PPT gene expression and
      their clinical side effects and therapeutic efficacy is discussed.

PMID- 1976802
TI  - Two types of voltage-dependent calcium current in rat somatotrophs are reduced by
      somatostatin.
AB  - 1. Somatotrophs were obtained from rat pituitary glands after dissociation,
      separation and enrichment on a continuous gradient of bovine serum albumin at
      unit gravity. Somatotrophs were enriched up to 85% in the heavy fractions (F8 and
      F9). 2. After identification by reverse hemolytic plaque assay, patch-clamp
      recording in the whole-cell mode was performed on somatotrophs. 3. Under voltage
      clamp conditions, two types of Ca2+ currents were recorded. From a holding
      potential of -70 mV, depolarizing voltage steps to potentials more positive than 
      50 mV activated a current which rapidly inactivated and which was very sensitive
      to Ni2+ but not to Cd2+. This current corresponds to T-type current. Depolarizing
      steps to potentials more positive than -30 mV from a holding potential of -40 mV
      triggered a current which slowly inactivated and which was very sensitive to Cd2+
      but not to Ni2+. This current corresponds to L-type current. 4. Application of
      somatostatin to the bath solution (10 nM) markedly reduced the amplitudes of both
      T- and L-type currents. Somatostatin decreased the conductance of L-type current
      without modifying its time- and voltage-dependent inactivation but its activation
      was not affected. However, somatostatin decreased the conductance of T-type
      currents, and also accelerated its time-dependent inactivation. Half-inactivation
      voltage of T-type current was shifted from -52 to -63 mV by somatostatin but no
      change was obtained in the current activation curve. 5. All these modifications
      in Ca2+ currents were abolished by a pre-treatment of the cultures with pertussis
      toxin (100 ng/ml, for 10 h). This pre-treatment also blocked the inhibitory
      effect of somatostatin on high-K(+)-stimulated growth hormone release. 6. Our
      results show that somatostatin acts on somatotrophs by attenuating the voltage
      dependent Ca2+ currents. These effects may contribute to a somatostatin-induced
      reduction in [Ca2+]i and the subsequent decline in growth hormone release.

PMID- 1976804
TI  - Abstracts from Panic and Anxiety: a Decade of Progress. An international
      conference. June 19-22, 1990, Geneva, Switzerland.

PMID- 1976803
TI  - Opioid actions on single nucleus raphe magnus neurons from rat and guinea-pig in
      vitro.
AB  - 1. Intracellular recordings were made from neurons of the nucleus raphe magnus
      (NRM) from rat (n = 128) and guinea-pig (n = 115). Two types of cells were found
      in each, primary (103 in rat, 27 in guinea-pig) and secondary cells (25 in rat,
      88 in guinea-pig). 2. Primary cells had input resistances of 186 +/- 9 M omega (n
      = 9) in rat and 255 +/- 50 M omega (n = 11) in guinea-pig. The action potential
      in each was about 1.5 ms in duration. Synaptic potentials were evoked by focal
      electrical stimulation and consisted of both gamma-aminobutyric acid (GABA) and
      excitatory amino acid components. 3. Morphine, [Met5]enkephalin (ME) and [D
      Ala2,N-Me-Phe4, Gly5-ol]enkephalin (DAMGO) depressed the amplitude of the GABA
      mediated synaptic potential by a maximum of 50-65% and had little effect on the
      excitatory amino acid-mediated synaptic potential. There was no effect of these
      opioids on the resting membrane potential or input resistance of primary cells in
      rat or guinea-pig. 4. Secondary cells had short duration action potentials (less
      than 1 ms) and an input resistance of 354 +/- 47 M omega in rat (n = 6) and 290
      +/- 40 M omega in guinea-pig (n = 15). The synaptic potential observed in the
      cells of this group was mediated by activation of only excitatory amino acid
      receptors. 5. ME hyperpolarized and/or abolished the spontaneous firing in
      sixteen out of twenty-four neurons in the secondary group from rat and eight out
      of eighty-four neurons from guinea-pig. ME induced an outward current at -60 mV
      that reversed polarity at potentials more negative than -92 +/- 3 mV in rat (n =
      6) and -98 +/- 2 mV in guinea-pig (n = 18). The reversal potential of the opioid
      current was shifted to less negative potentials when the external potassium
      concentration was increased, as predicted by the Nernst equation. 6. The
      morphology of the two types of cells were distinguishable in that primary cells
      were oval (29 x 18 microns in rat; 36 x 19 microns in guinea-pig) with two to
      four thick tapering dendrites that branched within 50 microns of the cell body.
      Secondary cells were generally round or oval (about 24 x 13 microns in rat; 27 x
      17 microns in guinea-pig) with two to five thin non-tapering dendrites.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 1976805
TI  - Hypothalamic regulation of circadian noradrenergic input to the chick pineal
      gland.
AB  - While the avian pineal gland contains circadian oscillators and photoreceptors
      capable of producing circadian rhythms of the hormone melatonin, it is
      extensively innervated by post-ganglionic fibers of the superior cervical ganglia
      which release norepinephrine (NE) rhythmically. Norepinephrine turnover is higher
      during subjective day than during subjective night. In mammals, this rhythmic
      input, which is higher in subjective night than subjective day, derives from the
      hypothalamic suprachiasmatic nuclei (SCN) and is essential for rhythmic melatonin
      production. The present study was designed to determine whether one of two
      candidates for the avian homologue of the mammalian SCN is necessary for rhythmic
      NE turnover in the chick pineal gland. Either electrolytic lesions or sham
      lesions were delivered to the periventricular preoptic nuclei (PPN) or to the
      visual suprachiasmatic nucleus (vSCN). After recovery, the rates of decline in
      [NE] were determined following pretreatment with alpha-methyl-p-tyrosine, a
      tyrosine hydroxylase inhibitor, at mid-subjective day or at mid-subjective night.
      Birds receiving sham surgeries in either PPN or vSCN and birds receiving lesions
      of the PPN exhibited rhythmicity in NE turnover. No rhythm of NE turnover could
      be determined in birds with ablated vSCN.

PMID- 1976806
TI  - Action of FMRFamide on longitudinal muscle of the leech, Hirudo medicinalis.
AB  - 1. Nerve terminals associated with longitudinal muscle in the leech show
      FMRFamide-like immunoreactivity. 2. Structure-activity studies using FMRFamide
      analogs show that the C-terminal RFamide portion of the molecule is crucial for
      biological activity on leech longitudinal muscle. 3. The putative protease
      inhibitor FA (Phe-Ala) increases the peak tension produced by longitudinal muscle
      in response to superfused FMRFamide and the majority of its analogs, suggesting
      the presence of peripheral proteases capable of degrading RFamide peptides. 4.
      FMRFamide decreases the relaxation rate of neurally evoked contractions of
      longitudinal muscle. FA also decreases the relaxation rate of neurally evoked
      contractions. 5. Intact and isolated muscle cells respond to superfused FMRFamide
      with a conductance increase, that leads to depolarization and often with a
      delayed conductance decrease as the membrane potential is restored to resting
      levels. 6. The depolarizing response of isolated muscle cells to FMRFamide is
      dependent on external calcium.

PMID- 1976807
TI  - Observations on the influence of active immunization against somatostatin on the
      reproductive performance of sheep and pigs.
AB  - Somatostatin (SRIF) is known to have inhibitory effects in a wide variety of
      tissues but a role in reproduction has not been described. The present studies
      describe the influence of SRIF immuno-neutralization on the reproductive
      performance of sheep and pigs. In experiment 1, Rambouillet x Suffolk ewe lambs
      were actively immunized against SRIF conjugated to ovalbumin (SI; n = 24) or were
      not immunized (CT; n = 32). Primary immunizations were initiated at weaning and
      boosters given at 4-week intervals, as well 10 days before breeding and lambing.
      Over two years, breeding periods were September and January (in-season) and May
      (out-of-season). Pregnancy rates were higher for SI than for CT ewes following
      both in-season (P less than 0.01) and out-of season breeding (P less than 0.06).
      The number of lambs born per ewe lambing was not affected by treatment. In
      experiment 2, Yorkshire x Landrace gilts were actively immunized against SRIF
      ovalbumin conjugate (n = 37) or were not immunized (n = 38). Primary
      immunizations were given at 39.8 +/- 1.5 kg body weight and boosters after 4
      weeks, 10 days before breeding and at 105 days of gestation. Some SI (n = 15) and
      CT gilts (n = 17) were slaughtered 10 days after estrus to determine ovulation
      rates. Remaining SI (n = 22) and CT (n = 21) gilts carried their litters to term.
      Ovulation rates tended to be higher (P less than 0.1) in SI than CT gilts (11.8
      +/- 0.6 vs. 10.7 +/- 0.4). There was no effect of treatment on pregnancy rates to
      initial breeding (86.4 vs. 90.5% for SI and CT gilts, respectively) but first
      litter size tended to be larger (P less than 0.07) for SI than for CT gilts (9.95
      +/- 0.34 vs. 9.00 +/- 0.38). There was no effect of treatment on litter growth
      performance during lactation. These data provide evidence that SRIF may be
      involved in the regulation of reproduction.

PMID- 1976808
TI  - Connective tissue disease in southeast Georgia. A community based study of
      immunogenetic markers and autoantibodies.
AB  - HLA antigens, C4 allotypes and T cell antigen receptor (TcR)beta DNA
      polymorphisms were determined in a community based study of connective tissue
      diseases (CTD). HLA-B8, DR3 and C4A null phenotypes occurred frequently in
      Caucasian patients with CTD, especially those with systemic lupus erythematosus
      (SLE), but were also more commonly found among healthy white controls of this
      southeast Georgia community. TcR beta gene polymorphisms also showed differential
      segregation patterns between patients with SLE and scleroderma. High frequencies
      of ANA and anti-ssDNA antibodies occurred among apparently healthy family members
      and local controls. Genetic factors predisposing to CTD in a community setting
      appear to be similar to those reported from referral centers.

PMID- 1976809
TI  - Lack of gene deletion for complement C4A deficiency in Japanese patients with
      systemic lupus erythematosus.
AB  - The frequency of C4A gene deletion was studied in Japanese patients with systemic
      lupus erythematosus (SLE) and was compared with healthy controls. DNA
      preparations were extracted from peripheral blood leukocytes from 59 patients
      with SLE and from 166 healthy persons, and digested by restriction enzymes. They
      were hybridized with C4 complementary DNA by the Southern blotting method and the
      deletion of C4A gene was judged from restriction fragment length polymorphism. At
      the same time phenotypic C4A deficiency (C4AQ0) was measured. Our results showed
      that the frequency of phenotypic C4A deficiency was 44.1% in Japanese patients
      with SLE and this value was comparable with that (43.2%) in Caucasian patients.
      On the other hand the deletion of C4A gene was not found in Japanese patients
      with SLE (0%), or in healthy controls (0.6%). Our results indicate that C4AQ0 may
      contribute to the pathogenesis of SLE beyond the ethnical differences but
      Japanese patients with SLE have a different genetic background from Caucasian
      patients with the C4A gene deleted.

PMID- 1976810
TI  - HIV associated systemic necrotizing vasculitis.
AB  - The spectrum of HIV associated rheumatic syndromes continues to expand as does
      our experience with the disease. The following is a case of HIV associated
      systemic necrotizing vasculitis documented by rectal biopsy. The patient was
      treated successfully with corticosteroids alone, and after 9 months of followup
      has no evidence of progression to frank AIDS.

PMID- 1976811
TI  - Termination of slow acting antirheumatic therapy in rheumatoid arthritis: a 14
      year prospective evaluation of 1017 consecutive starts.
AB  - During a continuous 14-year observation period we prospectively recorded clinical
      data on all patients with rheumatoid arthritis (RA) attending an outpatient
      clinic. Six hundred seventy-one patients received 1017 new administrations of
      slow acting antirheumatic drugs during more than 2000 patient years of
      observation. The median time to discontinuation for intramuscular gold,
      auranofin, hydroxychloroquine or penicillamine was 2 years or less, but was 4.25
      years for methotrexate (p = 0.008 vs all other drugs combined). Adverse reactions
      were a more common reason for discontinuation than efficacy, and both were less
      common in patients taking methotrexate (p less than 0.01). Neither disease
      duration, disease severity, or demographic factors were useful predictors of
      discontinuation. Since controlled clinical trials do not provide long-term
      outcome assessments, measurement of time to termination is a practical tool to
      estimate drug inefficacy.

PMID- 1976812
TI  - Synthesis of novel (aryloxy)propanolamines and related compounds possessing both
      class II and class III antiarrhythmic activity.
AB  - Several (aryloxy)propanolamines and related compounds (i.e. 5-13, 16-18, 20-24,
      27-33, 35, 37-39, 41, and 42) were synthesized and investigated for their class
      III electrophysiological activity and class II (beta-blocking) effects with use
      of in vitro and in vivo models. Structure-activity relationships are discussed
      for a series of 30 compounds. A number of these compounds prolonged the action
      potential duration at 95% repolarization of isolated canine cardiac Purkinje
      fibers by 20% (C20APD95) at concentrations of less than 1.0 microM, with no
      significant effects on cardiac conduction. beta-Adrenergic receptor binding
      studies showed that some of these compounds were 2-20 times more potent for
      cardiac beta 1 receptors than for beta 2 receptors. In particular, compounds 32,
      41, 1, and especially (S)-1 were found to be orally active class III agents in
      anesthetized mongrel dogs (1 or 3 mg/kg, id) and efficacious at suppressing
      programmed electrical stimulation induced arrhythmias in halothane-anesthetized
      dogs. The profile of these compounds was similar to that found for sotalol.
      Compound (S)-1, which was more potent than sotalol in the PES study and
      equieffective in the halothane/epinephrine dog model, is being investigated
      further as a combined class III/II antiarrhythmic agent.

PMID- 1976813
TI  - 2-Phenyl-2-(1-hydroxycycloalkyl)ethylamine derivatives: synthesis and
      antidepressant activity.
AB  - A series of 2-phenyl-2-(1-hydroxycycloalkyl)ethylamine derivatives was examined
      for the ability to inhibit both rat brain imipramine receptor binding and the
      synaptosomal uptake of norepinephrine (NE) and serotonin (5-HT). Neurotransmitter
      uptake inhibition was highest for a subset of 2-phenyl-2-(1
      hydroxycyclohexyl)dimethylethylamines in which the aryl ring has a halogen or
      methoxy substituent at the 3- and/or 4-positions. Potential antidepressant
      activity in this subset was assayed in three rodent models--the antagonism of
      reserpine-induced hypothermia, the antagonism of histamine-induced ACTH release,
      and the ability to reduce noradrenergic responsiveness in the rat pineal gland.
      An acute effect seen in the rat pineal gland with several analogues, including 1
      [1-(3,4-dichlorophenyl)-2-(dimethylamino)ethyl]cyclohexanol (23) and 1-[2
      (dimethylamino)-1)-(4-methoxyphenyl)ethyl]cyclohexanol (4), was taken as a
      possible correlate of a rapid onset of antidepressant activity. Compound 4
      (venlafaxine) is presently undergoing clinical evaluation.

PMID- 1976814
TI  - Linkage studies and deletion screening in choroideremia.
AB  - Fourteen families with choroideremia (TCD) have been examined for linkage to nine
      genetic markers located on the proximal long arm of the X chromosome. Linkage to
      three markers (DXYS1, DXS72, DXS3) located in Xq21 was found with a four point
      lod score of 8.25. No evidence of submicroscopic deletions was observed using
      DXS233 and DXS232, both thought to lie within about 1 Mb of the TCD gene.

PMID- 1976815
TI  - Metallothionein Mto gene of Drosophila melanogaster: structure and regulation.
AB  - We report the sequence of the Mto gene, one of the two known metallothionein
      genes of Drosophila melanogaster, and compare its structure with that of the
      other metallothionein gene, Mtn. The main structural features are the presence of
      a small intron (61 base-pairs), the presence of four potential MREs (metal
      regulatory elements) and the absence of a TATA box in the promoter region. Of all
      metals tested, Hg2+, Cd2+ and Cu2+ are the most efficient ions for inducing an
      increase in Mto gene transcription. The Mto and Mtn genes are differentially
      regulated during normal development. Transcription of Mto is detected early in
      embryogenesis (0 to 3 h) and persists to the third larval instar, while Mtn
      expression starts later in embryogenesis (12 to 15 h) and is thereafter
      maintained throughout larval development and adult stages. Sequencing of the Mto
      protein is in good agreement with the nucleic acid data. Surprisingly, attempts
      to isolate and characterize the Mtn protein were unsuccessful. Several lines of
      evidence suggest that this metallothionein is rapidly incorporated after its
      synthesis into lysosomes, where it would be processed in a way that would not
      permit its purification. The function of the Mtn protein thus appears to be
      mainly related to detoxification processes. The pattern of expression of Mto
      suggests that this gene may be involved in the control of metal homeostasis
      during development.

PMID- 1976816
TI  - Nucleotide sequence of nine protein-coding genes and 22 tRNAs in the
      mitochondrial DNA of the sea star Pisaster ochraceus.
AB  - We have cloned and sequenced over 9 kb of the mitochondrial genome from the sea
      star Pisaster ochraceus. Within a continuous 8.0-kb fragment are located the
      genes for NADH dehydrogenase subunits 1, 2, 3, and 4L (ND1, ND2, ND3, and ND4L),
      cytochrome oxidase subunits I, II, and III (COI, COII, and COIII), and adenosine
      triphosphatase subunits 6 and 8 (ATPase 6 and ATPase 8). This large fragment also
      contains a cluster of 13 tRNA genes between ND1 and COI as well as the genes for
      isoleucine tRNA between ND1 and ND2, arginine tRNA between COI and ND4L, lysine
      tRNA between COII and ATPase 8, and the serine (UCN) tRNA between COIII and ND3.
      The genes for the other five tRNAs lie outside this fragment. The gene for
      phenylalanine tRNA is located between cytochrome b and the 12S ribosomal genes.
      The genes for tRNA(glu) and tRNA(thr) are 3' to 12S ribosomal gene. The tRNAs for
      histidine and serine (AGN) are adjacent to each other and lie between ND4 and
      ND5. These data confirm the novel gene order in mitochondrial DNA (mtDNA) of sea
      stars and delineate additional distinctions between the sea star and other mtDNA
      molecules.

PMID- 1976817
TI  - Detection of human T-cell leukemia virus type I (HTLV-I) provirus in an infected
      cell line and in peripheral mononuclear cells of blood donors by the nested
      double polymerase chain reaction method: comparison with HTLV-I antibody tests.
AB  - Human T-cell leukemia virus type I (HTLV-I) provirus DNA from the cultured cell
      line HUT 102 and from peripheral mononuclear cells (PBMC) of anti-HTLV-I antibody
      positive Japanese blood donors was detected by the nested double polymerase chain
      reaction (PCR) method. This procedure consists of a first amplification and a
      second amplification with the products of the first amplification and primers
      interior to the first primers. Using this method, we demonstrated that it is
      possible to detect single-template DNA. Polyacrylamide gel electrophoresis of the
      nested double PCR products, with our primers, revealed three bands with excess
      amounts of template DNA, two bands with moderate amounts, and a single band with
      limited amounts. The amount of provirus in PBMC was roughly estimated from the
      results of the nested double PCR. Particle agglutination (PA) assays and indirect
      immunofluorescence testing (IF) with mixed MT-2 cells and Molt-4 cells as targets
      to detect anti-HTLV-I antibody were performed, and the results were compared with
      those of the nested double PCR of the pX region. None of the 101 PA-negative
      samples were positive in either the IF or PCR test. Of the 155 samples that were
      antibody positive by the PA assay, 57 were positive by both PCR and IF.
      Furthermore, the results of the IF and PCR tests coincided completely. It was
      therefore concluded that the IF method is most appropriate for confirmation of
      the PA assay currently used in most diagnostic laboratories and blood centers.

PMID- 1976818
TI  - In vivo polyclonal B-lymphocyte activation elicited by murine viruses.
AB  - Viruses such as lactate dehydrogenase-elevating virus and adenovirus induce in
      vivo a polyclonal activation of murine B lymphocytes, followed by a marked
      increase in the production of immunoglobulin G2a (IgG2a). The role of T
      lymphocytes in this phenomenon was studied by injection of an anti-CD4 monoclonal
      antibody able to inhibit the T-helper function. This treatment profoundly
      depressed the production of IgG2a, whereas it had no effect on the proliferation
      of B cells. Activated B cells obtained from such infected and treated mice
      remained able to produce various immunoglobulin isotypes after exposure to an
      appropriate stimulus. In particular, gamma interferon, which is known to be
      secreted after viral infection, induced the production of IgG2a. These
      observations support the hypothesis that the influence of viruses on the switch
      of immunoglobulins is mediated by T-helper lymphocytes.

PMID- 1976819
TI  - Clearance of a persistent paramyxovirus infection is mediated by cellular immune
      responses but not by serum-neutralizing antibody.
AB  - Infection of the lungs of immunodeficient mice with the paramyxovirus simian
      virus 5 (SV5) was prolonged compared with the time course of infection in
      immunocompetent mice. Although there was a significant increase in both viral RNA
      and proteins, little infectious virus was produced. Adoptive transfer of immune
      lymphocytes (isolated from the spleens of mice previously infected with SV5) but
      not of nonimmune lymphocytes increased the speed of clearance of virus from the
      lungs of immunodeficient mice. In contrast, passive transfer of a pool of
      neutralizing monoclonal antibodies specific for the HN and F glycoproteins of SV5
      did not have a significant effect on the speed of clearance of virus.
      Furthermore, no significant increase in the rate of virus clearance was observed
      upon adoptive transfer of purified immune B lymphocytes to SV5-infected
      immunodeficient mice despite production by the mice of high titers of
      neutralizing antibodies. Evidence is presented that CD8+ effector cells are
      primarily responsible for the clearance observed. The general significance of
      these results with respect to immune clearance of persistent virus infections is
      discussed.

PMID- 1976820
TI  - Lymphotoxin activation by human T-cell leukemia virus type I-infected cell lines:
      role for NF-kappa B.
AB  - Human T-cell leukemia virus type I (HTLV-I)-infected T-cell lines constitutively
      produce high levels of biologically active lymphotoxin (LT; tumor necrosis factor
      beta) protein and LT mRNA. To understand the regulation of LT transcription by
      HTLV-I, we analyzed the ability of a series of deletions of the LT promoter to
      drive the chloramphenicol acetyltransferase (CAT) reporter gene in HTLV-I
      positive MT-2 cells. The smallest LT promoter fragment (-140 to +77) that was
      able to drive CAT activity contained a site that was similar to the
      immunoglobulin kappa-chain NF-kappa B-binding site. Since the HTLV-I tax gene
      activates the nuclear form of NF-kappa B, this finding suggested a possible means
      of HTLV-I activation of LT production. We found that the LT kappa B-like site
      specifically formed a complex with NF-kappa B-containing nuclear extract from MT
      2, C81-66-45, and other activated T cells. Mutation of the LT kappa B site in the
      context of the LT promoter (-293 to +77) (mutant M1) reduced the ability of the
      promoter to drive the CAT gene in HTLV-I-infected and noninfected human T-cell
      lines. These data suggest a general role for NF-kappa B activation in the
      induction of LT gene transcription. Activation of LT in HTLV-I-infected cells may
      explain the pathology associated with HTLV-I infection, including the
      hypercalcemia that is prevalent in adult T-cell leukemia.

PMID- 1976821
TI  - Efficacious control of cytomegalovirus infection after long-term depletion of
      CD8+ T lymphocytes.
AB  - Although the relative contribution of different immune effector functions to
      clearing tissues of cytomegalovirus is controversial, the contribution of CD8+ T
      lymphocytes has generally been accepted as essential. In this report, we show
      that under certain conditions the CD8+ T-lymphocyte subset can be dispensable for
      clearance of cytomegalovirus. Mice depleted of the CD8+ T-lymphocyte subset
      eliminated infectious virus with a clearance kinetics similar to that of normal
      mice. Adoptive transfer studies revealed that the limitation of virus spread
      required the cooperation between the CD4+ subset and other cells. Comparison
      between protective functions generated in fully immunocompetent and in CD8- mice
      demonstrated that elimination of the CD8+ subset before infection altered the
      quality of the antiviral immune response. The compensatory protective activity
      gained by CD4+ cells in CD8- mice was absent in normal mice recovering from virus
      infection.

PMID- 1976822
TI  - Lymphocyte subset alterations and viral determinants of immunodeficiency disease
      induction by the feline leukemia virus FeLV-FAIDS.
AB  - The FeLV-FAIDS strain of feline leukemia virus consistently induces fatal
      immunodeficiency. To investigate the immunopathogenesis and viral genetic
      determinants responsible for the induction of immunodeficiency disease in vivo,
      we have generated chimeras between the two major viral genomes in the original
      virus isolate, designated common form clone 61E and major variant clone 61C,
      which were molecularly cloned directly from DNA of the same animal and tissue.
      Each of three 61E/C chimeras, containing at minimum a 34-amino-acid segment
      (including a 6-amino-acid insertion and one amino acid substitution) near the C
      terminus of the 61C surface glycoprotein (gp70), induced fatal immunodeficiency
      disease in all (12 of 12) infected animals over a course of 33 +/- 10 weeks. By
      contrast, animals infected with virus 61E, although persistently antigenemic,
      remained asymptomatic throughout a 48-week observation period. Beginning 14 weeks
      after infection, a significant decrease (8 to 10%) in the percent of circulating
      CD4+ T lymphocytes developed in the 61E/C chimera-infected cats, compared with
      either 61E-infected or control animals. At this time, no significant changes were
      seen in CD8 cells, B cells, or mitogen-induced blastogenesis. Prior to this
      initial decline in CD4 cells, the ability of all antigenemic 61E/C-infected cats
      to generate a primary antibody response to the T-cell-dependent antigen keyhole
      limpet hemocyanin was markedly impaired, whereas all 61E-infected cats, one 61E/C
      infected but nonviremic cat, and all uninfected control cats produced normal
      antibody responses. The results reported here demonstrate that a major
      determinant of in vivo immunodeficiency induction by FeLV-FAIDS is contained
      within a 34-amino-acid C-terminal segment of its surface glycoprotein and that
      this gp70 alteration determines the early and persistent deficits in CD4+ T
      lymphocytes and T-cell-dependent antibody responses. We hypothesize that these
      early immunologic alterations could result from early deletion of a CD4+ helper T
      cell subset.

PMID- 1976823
TI  - Factors affecting cellular tropism of human immunodeficiency virus.
AB  - To evaluate the basis of the slow growth of many human immunodeficiency virus
      strains in monocytes/macrophages, various stages of the virus life cycle have
      been studied for their possible contribution to viral tropism. Although we found
      that monocytic U937 cells had a higher percentage of CD4-positive cells than T
      lymphoid H9 cells, the human immunodeficiency virus strain grew much less
      efficiently in the monocytic line. Viral tropism was primarily determined during
      the early stages of the virus cycle, that is, sometime between binding of the
      virus to the cell surface and reverse transcription of viral genomic RNA. Once
      the virus entered the host cell, reverse transcription, use of the long terminal
      repeat, RNA expression, and production of virus particles was about as efficient
      in monocytes as in T cells. Thus, during viral entry into the host cell cytoplasm
      there is a major limiting event that is particularly inefficient in U937 cells
      and possibly in all monocytes/macrophages.

PMID- 1976824
TI  - Two receptors are required for antibody-dependent enhancement of human
      immunodeficiency virus type 1 infection: CD4 and Fc gamma R.
AB  - Evidence of antibody-dependent enhancement of human immunodeficiency virus type 1
      (HIV-1) infection via Fc receptor (FcR) was published previously (A. Takeda, C.
      U. Tuazon, and F. A. Ennis, Science 242:580-583, 1988). To define the entry
      mechanism of HIV-1 complexed with anti-HIV-1 antibody, we attempted to determine
      the receptor molecules responsible for mediating enhancement of HIV-1 infection
      of monocytic cells. Monoclonal antibodies to FcRI for immunoglobulin G
      substantially blocked antibody-dependent enhancement of HIV-1 infection.
      Furthermore, we demonstrate a requirement for the CD4 molecule in antibody
      enhanced HIV-1 infection via FcR. Soluble CD4 prevented infection by HIV-1
      antibody-treated virus, and enhancement of infection of virus-antibody complexes
      was abrogated by a monoclonal antibody to CD4 (anti-Leu3a antibody). Treatment of
      human macrophages with an anti-CD4 antibody also inhibited antibody-enhanced HIV
      1 infection of macrophages, supporting our contention that antibody-dependent
      enhancement of HIV-1 infection via FcR requires CD4 interaction with the virus
      glycoprotein.

PMID- 1976825
TI  - In vivo selection of lymphocyte-tropic and macrophage-tropic variants of
      lymphocytic choriomeningitis virus during persistent infection.
AB  - This study demonstrates cell-specific selection of viral variants during
      persistent lymphocytic choriomeningitis virus infection in its natural host. We
      have analyzed viral isolates obtained from CD4+ T cells and macrophages of
      congenitally infected carrier mice and found that three types of variants are
      present in individual carrier mice: (i) macrophage-tropic, (ii) lymphotropic, and
      (iii) amphotropic. The majority of the isolates were amphotropic and exhibited
      enhanced growth in both lymphocytes and macrophages. However, some of the
      lymphocyte-derived isolates grew well in lymphocytes but poorly in macrophages,
      and a macrophage-derived isolate replicated well in macrophages but not in
      lymphocytes. In striking contrast, the original wild-type (wt) Armstrong strain
      of lymphocytic choriomeningitis virus that was used to initiate the chronic
      infection and from which the variants are derived grew poorly in both lymphocytes
      and macrophages. These three types of variants also differed from the parental
      virus in their ability to establish a chronic infection in immunocompetent hosts.
      Adult mice infected with the wt Armstrong strain cleared the infection within 2
      weeks, whereas adult mice infected with the variants harbored virus for several
      months. These results suggest that the ability of the variants to persist in
      adult mice is due to enhanced replication in macrophages and/or lymphocytes. This
      conclusion is further strengthened by the finding that the variants and the
      parental wt virus grew equally well in mouse fibroblasts and that the observed
      growth differences were specific for cells of the immune system.

PMID- 1976826
TI  - Immunologic abnormalities in pathogen-free cats experimentally infected with
      feline immunodeficiency virus.
AB  - Blood mononuclear cells from 47 cats experimentally infected with feline
      immunodeficiency virus (FIV) were examined by using monoclonal antibodies
      directed against feline CD4 and CD8 homologs, a pan-T-cell antigen, and cell
      surface immunoglobulin. Significant inversion of the CD4+/CD8+ T-cell ratio was
      observed only in cats that were infected for 18 months or more. This inversion
      was associated with a decrease in the absolute numbers of CD4+ T cells and a
      concomitant increase in CD8+ cells. However, the total numbers of circulating T
      and B cells were not significantly reduced. Cats infected with FIV for 24 to 28
      months also had significantly elevated levels of serum immunoglobulin G (IgG),
      but normal levels of IgA and IgM. The long-term decline in CD4+ T cells and
      hypergammaglobulinemia observed in FIV-infected cats resemble the abnormalities
      occurring in humans after human immunodeficiency virus infection.

PMID- 1976827
TI  - In vivo cellular tropism of human T-cell leukemia virus type 1.
AB  - To establish the phenotype of human T-cell leukemia virus type 1 (HTLV-1)
      infected cells in peripheral blood, the polymerase chain reaction was used to
      detect and quantitate viral DNA in subpopulations of leukocytes obtained from
      patients with tropical spastic paraparesis and asymptomatic carriers. HTLV-1
      could not be detected in peripheral blood mononuclear cells thoroughly depleted
      of T lymphocytes (E- CD3-), nor could it be detected in highly enriched
      populations of B lymphocytes (E- CD19+), monocytes (E- CD14+), or natural killer
      cells (E- CD16+). T lymphocytes were strongly positive for HTLV-1, and
      fractionation of this population revealed that 90 to 99% of the HTLV-1 DNA
      segregated with the CD4+ CD8- and CD45RO+ subsets. No difference between the cell
      type distribution of HTLV-1 in the asymptomatic carrier and the subjects with
      tropical spastic paraparesis was evident. Southern hybridization of genomic DNA
      prepared from the peripheral blood of HTLV-1 carriers indicated that up to 10% of
      circulating leukocytes may carry the HTLV-1 provirus.

PMID- 1976828
TI  - Surgical procedures in the management of Takayasu's arteritis.
AB  - Takayasu's arteritis is an inflammatory arteriopathy that often progresses to
      obliteration of multiple large arteries. Variable results have been reported
      after medical and surgical management. Twenty female patients with Takayasu's
      arteritis were treated from 1973 to 1989. Eleven (55%) patients had hypertension.
      Upper or lower extremity ischemia was present in 12 (60%) patients and
      cerebrovascular insufficiency in seven (35%). Nine patients initially managed
      with corticosteroids had no improvement in signs or symptoms of arterial
      insufficiency. Eleven patients had 16 vascular procedures for the following
      indications: renovascular hypertension (6), extremity ischemia (5),
      cerebrovascular insufficiency (2), dilation ascending aorta with aortic
      insufficiency (1), thoracic aortic aneurysm (1), abdominal aortic aneurysm (1).
      Procedures included aortorenal bypass (5), carotid-subclavian, axillary, or
      brachial bypass (4), aorto-carotid bypass (2), aneurysm resection (2), supra
      celiac aorto-femoral bypass (1), ascending aorta/aortic valve replacement (1),
      and nephrectomy (1). Clinical improvement occurred in all patients. There were no
      operative deaths. All are alive at a mean follow-up of 5.75 years (6 months to 16
      years). Revision of the initial reconstruction has been required for recurrent
      renovascular hypertension in one patient and extremity ischemia in another. The
      other nine patients remain symptomatically improved. Symptomatic Takayasu's
      arteritis frequently requires arterial reconstruction. Symptomatic improvement
      and excellent long-term graft patency can be expected after arterial
      reconstruction.

PMID- 1976829
TI  - [Comparative pharmacokinetics of pipecuronium bromide, pancuronium bromide and
      vecuronium bromide in anesthetized man].
AB  - The pharmacokinetics of pipecuronium bromide was studied in 9 male patients (ASA
      class 1-2, 20-65 years of age). Following a single intravenous dose of
      pipecuronium 0.08 mg.kg-1, plasma levels were measured by capillary gas
      chromatography. Plasma concentration-time curves were evaluated by fitting the
      data to a bi-exponential equation. The pharmacokinetic parameters of pipecuronium
      were compared with those of pancuronium (0.08 mg.kg-1) and vecuronium (0.08 mg.kg
      1) previously obtained under the same anesthesia (66% N2O, 33% O2 and 1%
      halothane). With pipecuronium, following pharmacokinetic parameters were
      obtained; distribution half-life; T1/2 alpha = 3.9 +/- 0.7 min (mean +/- SEM),
      elimination half-life; T1/2 beta = 102 +/- 12 min, volume of the central
      compartment; V1 = 95 +/- 13 ml.kg-1, volume of distribution at steady state; Vdss
      = 264 +/- 41 ml.kg-1, clearance; Cl = 1.8 +/- 0.2 ml.min-1.kg-1. Microconstants
      of two-compartment open models (k12, k21, k10) were also calculated. Using Mann
      Whitney's U-test, these parameters of pipecuronium were compared with those of
      pancuronium (n = 3) and vecuronium (n = 4). V1 and Vdss of pipecuronium were
      significantly larger than those of pancuronium (V1; 38 +/- 12 ml.kg-1 and Vdss;
      120 +/- 4 ml.kg-1) (both P less than 0.10). Reflecting the larger central volume
      of pipecuronium, pipecuronium tended to have a larger clearance than that of
      pancuroniumu (Cl; 1.1 +/- 0.2 ml.min-1.kg-1).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1976830
TI  - [Effects of the dynorphin derivative "E2078" on hemodynamics and plasma
      catecholamines in dogs].
AB  - Recently, a dynorphin derivative (E2078) is synthesized as a kappa-agonist.
      Unlike dynorphin, E2078 is easily inactivated by peptidases. In this study,
      hemodynamic effects of E2078 were investigated in 54 adult mongrel dogs under
      enflurane anesthesia. They were divided into 6 groups according to the dose of
      E2078 administrated. In the small dosage groups (0.05, 0.1 mg.kg-1), systemic
      blood pressure was reduced due to cardiac depression. In the large dosage groups
      (1.0 mg.kg-1, 10 mg.kg-1), the systemic blood pressure decreased due to
      vasodilation while the cardiac output increased. In the 1.0 mg.kg-1 group, the
      heart rate decreased, but it increased in the 10 mg.kg-1 group. This difference
      could be caused by decreased plasma catecholamines in the 1.0 mg.kg-1 group, and
      their increase in the 10 mg.kg-1 group. The changes in plasma catecholamine
      levels might be a factor contributing to circulatory depression due to decreased
      norepinephrine release from the sympathetic nerve endings by E2078 as observed
      following administration of other kappa-ligands. Another factor for hemodynamic
      depression would be a direct action of E2078 to dilate vascular bed.

PMID- 1976831
TI  - [Effects of E2078, a new dynorphin derivative, on pituitary-adrenocortical
      functions in dogs].
AB  - E2078, a new analgesic is a dynorphin derivative. E2078 shows strong affinity to
      kappa receptors and is not rapidly cleaved by peptidases. This analgesic is also
      considered to be free of tolerance and dependence. In the present study, to
      determine the effect of E2078 on pituitary-adrenocortical function the author
      administered E2078 (0.001, 0.05, 0.1, 1.0, 10.0 mg.kg-1) by intramuscular
      injection to 38 adult mongrel dogs under enflurane anesthesia (1.0%) and then
      investigated the changes in the plasma concentrations of ACTH, cortisol, beta
      endorphin, PRA, aldosterone and ADH. In the animal groups which received E2078 at
      dosages of 0.001, 0.05, 0.1, and 1.0 mg.kg-1, no significant differences in the
      plasma concentrations of each hormone were detected compared with the control
      group which received physiological saline by intramuscular injection. However, in
      the dog group which received E2078 at 10.0 mg.kg-1, the plasma concentrations of
      PRA and aldosterone were significantly elevated.

PMID- 1976832
TI  - Striatal glutamic acid and gamma-aminobutyric acid in transient cerebral ischemia
      in spontaneously hypertensive rats.
AB  - A massive striatal dopamine release (241-fold increase) was observed in a
      previous study during acute cerebral ischemia in rats. In this study,
      extracellular levels of glutamic acid (GLU), gamma-aminobutyric acid (GABA) and
      lactic acid were simultaneously determined using in vivo brain dialysis in the
      striatum of spontaneously hypertensive rats during cerebral ischemia and after
      recirculation. Extracellular GABA levels increased to 932 +/- 75% (mean +/- SEM)
      of the resting level and GLU increased to 390 +/- 63% during 20 min ischemia.
      Although ischemia-induced release of GLU and GABA was demonstrated in this study,
      the degree of increase was smaller than that of dopamine. These findings may be
      relevant to the pathophysiology of cerebral ischemia in the striatum.

PMID- 1976833
TI  - [Severe pancytopenic episodes in two cases with mosquito-allergy].
AB  - Two young females were admitted one by one because of peculiar skin eruptions
      suggesting mosquito-allergy and severe pancytopenia with normo-hypercellular bone
      marrow. The outcome of the first case was fatal on account of severe
      pancytopenia, immune deficiency and marked jaundice 14 months after the initial
      pancytopenic episode. In the post-mortem examination, HMR (histiocytic medullary
      reticulosis) was highly suggestive since hepatosplenomegaly with increase of
      Kupffer cells and large histiocytes including some atypical cells were detected.
      The second patient was treated with splenectomy because the past treatment were
      unsatisfactory in the first case and another cases in literatures. After the
      operation, the patient sustained almost normal blood cell level for 11 months
      without any treatment. As for the histopathological findings of resected spleen
      and lymphnodes, some erythrophagocytic mature histiocytes were found, but no
      atypical cells was detected. The relationship with pancytopenia, mosquito-allergy
      and HMR was discussed on the two cases and literatures.

PMID- 1976834
TI  - [Genetic diagnosis in haemophiliacs (haemophilia A, B, carrier)].

PMID- 1976835
TI  - [Gene diagnosis of hereditary blood coagulation factor disorders (except for
      hemophilia)].

PMID- 1976836
TI  - [Nucleic acid hybridization method in clinical microbiology].

PMID- 1976837
TI  - [Metabolic disorders--from biochemistry to DNA diagnosis].

PMID- 1976838
TI  - [DNA analysis of leukemia].

PMID- 1976840
TI  - [Magnesium deficiency dermatitis--changes in leukotriene levels and effects of
      azelastine hydrochloride on the dermatitis and leukotriene B4].
AB  - To estimate the pathogenesis of magnesium deficiency dermatitis (MDD) in the
      hairless rats fed with a hypomagnesic diet, plasma concentrations of leukotrienes
      (LTB4, LTC4, LTD4) were measured. Inhibitory effect of azelastine hydrochloride
      (AZ), which is known as an inhibitor of 5-lipoxygenase, on MDD was also
      evaluated. In the hairless rats with magnesium deficiency condition, plasma level
      of leukotriene B4 was increased, whereas LTC4 and LTD4 showed no changes. In AZ
      administered rats, MDD was depressed with the dose-dependent tendency. However,
      the decrease of LTB4 level did not follow therapeutic effect of AZ for gross
      appearance of dermatitis. These results indicated that development of MDD
      associates with increase of LTB4, but its pathogenetic role still remains
      unknown, and inhibitory effect of AZ against MDD not based on reduction of LTB4
      production.

PMID- 1976839
TI  - [Expression of gamma-glutamyl transpeptidase related to the tumor differentiation
      on squamous cell carcinoma of human skin].
AB  - gamma-Glutamyl transpeptidase (gamma-GTP) has been noticed as one of the useful
      markers for malignant transformation of the skin. But the role and mechanism of
      the induction of gamma-GTP in skin carcinogenesis had not yet been studied. In
      this report, the authors studied the relationship between gamma-GTP activity and
      tumor differentiation in squamous cell carcinoma of human skin (SCC). Ten cases
      of SCC were examined on intensity and localization of the activity of gamma-GTP
      histochemically by the method of Rutenberg. gamma-GTP activity was found to be
      more intense in well differentiated SCC than in poorly differentiated SCC. On the
      other hand, localization pattern of gamma-GTP activity in SCC was not always
      related to the tumor grade. We concluded that expression of gamma-GTP activity in
      SCC may reflects the modulating cell differentiation rather than cell
      proliferation in malignant transformation of the skin. And some of the typical
      cases were presented.

PMID- 1976841
TI  - Hepatitis B core antigen specific CD4 response in peripheral blood.
AB  - The proliferative response of peripheral blood CD4+ T cells to recombinant
      hepatitis B core antigen (rHBcAg) has been studied in patients with chronic
      active hepatitis (CAH) type B (CAH-B), CAH-nonA nonB, and normal volunteers. CD4+
      T cells from patients with CAH-B indicated a significant proliferative response
      to rHBcAg in the presence of non-T antigen presenting cells. In contrast, there
      was no apparent T cell reaction to rHBcAg in patients with CAH-nonA nonB and
      healthy volunteers. We suggested the possibility of CD4-mediated HBcAg specific
      response even in the peripheral blood compartments of HBcAg-responsive CAH-B
      patients.

PMID- 1976842
TI  - [Renal failure associated with polyarteritis nodosa].
AB  - We reported 5 patients with renal failure associated with polyarteritis nodosa
      (PN). In all patients the renal dysfunction became apparent from 2 to 4 weeks
      after the onset of fever or neuromuscular symptoms with laboratory findings
      supporting marked inflammatory process and took the course of either acute or
      rapidly progressive renal failure. The clinical diagnoses on admission were
      variable; fever of unknown origin, peptic ulcer disease, polyneuritis multiplex,
      disseminated intravascular coagulation and Buerger's disease. Microscopic
      examination of the kidneys in 3 by renal biopsy and in 2 by autopsy revealed
      crescentic glomerulonephritis without immunoglobulin deposit, segmental
      necrotizing glomerulonephritis, marked inflammatory infiltrate around the
      glomeruli, granulomatous lesion, tubular necrosis and cortical necrosis other
      than necrotizing vasculitis. The outcomes were favorable with prednisolone
      monotherapy in two patients who had biopsy-proven diagnosis and treatment early
      in the course. Of all PN the prevalence of renal involvement is considered to be
      about 70%, the prognosis of which has been considered very poor. However it seems
      possible to alter fatal outcome of this disease by starting treatment with
      confident histological proof early in the disease process.

PMID- 1976844
TI  - Intrinsic pressor activity of midaglizole, an alpha-2 adrenoceptor antagonist, in
      pithed rats.
AB  - Midaglizole (3 and 30 mg/kg, i.v.) increased blood pressure in pithed rats. The
      pressor response was not inhibited by intravenous prazosin (0.3 mg/kg), yohimbine
      (1 mg/kg), ketanserin (1 mg/kg) or diphenhydramine (5 mg/kg). Diltiazem (1 mg/kg)
      antagonized the hypertension. Idazoxan (10 mg/kg) also increased blood pressure,
      and the pressor response was inhibited by prazosin, but not by yohimbine. These
      results suggest that the vascular effect of midaglizole is due to a mechanism
      different from that of idazoxan.

PMID- 1976845
TI  - [Effects of beta-antagonists and beta 1-partial agonists on the pulmonary pressor
      response to 5-HT].
AB  - The effects of beta-antagonists (propranolol, pindolol, atenolol) and beta 1
      partial agonists (xamoterol, denopamine) on the pulmonary circulation, and on the
      pressor response to 5-HT were investigated and compared with those of a beta
      agonist, isoproterenol. These agents (at doses of 0.002-20 mg) were administrated
      into the isolated lung lobe perfusion system excised from mongrel dogs (7-12 kg
      in weight). Under standard conditions (mean pulmonary inflow pressure, 15 mmHg;
      mean outflow pressure, 5 mmHg), propranolol and atenolol had no effect on
      pulmonary vascular resistance (PVR) at the tested doses, but pindolol which has
      intrinsic sympathomimetic activity (ISA) and two beta 1-partial agonists
      significantly decreased PVR in a dose-dependent manner (each n = 7).
      Isoproterenol, up to a dose of 0.2 mg, markedly decreased PVR, but induced
      vasoconstriction in larger doses (n = 7). Propranolol and xamoterol similarly
      reduced the pressor response to 30 micrograms of 5-HT from a dose of 2 mg, and
      these inhibitory actions were greater than those of the other drugs. Pindolol and
      denopamine inhibited the 5-HT response in a dose of 20 mg, whereas atenolol only
      augmented the response in a dose-dependent manner. In conclusion, beta
      antagonists with ISA (including beta 1-partial agonist activity) can dilate the
      pulmonary vessels in a dose-dependent manner, but not beta-antagonists without
      ISA. Furthermore, the 5-HT inhibitory effects caused by relatively large doses of
      beta-antagonists, except for atenolol, may be related to the 5-HT receptor
      blockade or other unknown mechanisms, including calcium influx or prostaglandin
      synthesis, but not to the beta-receptor blockade.

PMID- 1976843
TI  - Effects of bunazosin, a selective alpha 1-adrenergic blocking agent, on
      myocardial energy metabolism in ischemic dog heart.
AB  - Effects of a selective alpha 1-adrenergic blocking agent, bunazosin, on
      myocardial energy metabolism in the ischemic heart were studied. Ischemia was
      induced by ligating the left anterior descending coronary artery of the dog
      heart. Bunazosin was injected intravenously either 5 or 20 min before coronary
      artery ligation. Hearts were removed 3 min after coronary ligation and used for
      determination of the levels of cardiac tissue metabolites. Ischemia decreased the
      levels of ATP, creatine phosphate, glycogen and glucose, and increased the levels
      of ADP, AMP, hexose monophosphates and lactate. The energy charge potential (ECP)
      calculated was decreased by ischemia. Pretreatment with bunazosin inhibited the
      decrease in ATP and the increase in AMP caused by ischemia, resulting in the high
      value of ECP in the ischemic myocardium. Bunazosin also prevented the changes in
      carbohydrate metabolism caused by ischemia. It is concluded that bunazosin may
      reduce the influence of ischemia on the myocardium.

PMID- 1976846
TI  - Restriction fragment length polymorphism for the Yc subunit gene of rat liver
      glutathione S-transferase.
AB  - An altered expression of the Yc subunit gene of rat glutathione S-transferase
      (GST) in the liver of the LEC rat, which is a mutant strain with spontaneous
      hereditary hepatitis associated with severe jaundice, has been reported. To
      provide further information concerning the structure of the Yc subunit gene, we
      carried out the Southern blot hybridization analysis of DNA samples from rats of
      eight different inbred strains including LEC with cDNA complementary to mRNA
      specific for the Yc subunit of rat liver GST as a probe. The hybridization
      patterns of the DNA samples from rats belonging to the different inbred strains
      showed interstrain variation in the length of restriction fragments with four
      restriction endonucleases. Since the DNA samples prepared from several rats of
      one inbred strain gave an identical hybridization pattern, the restriction
      fragment patterns for the Yc gene could be used as markers for genetic monitoring
      of inbred rat strains. Although the altered expression of Yc-Yc activity of GST
      has been observed in the liver of the LEC rat, the characteristic changes in the
      gene structure of the Yc subunit of LEC rat were not detected in the present
      hybridization analysis.

PMID- 1976847
TI  - [Results of a 10-year prospective study of patients with ischemic heart disease].
AB  - The paper analyses the results of a 10-year prospective study of 396 patients
      with coronary heart disease concurrent with stable angina pectoris of different
      functional classes without serious concomitant diseases. In all the patients.
      coronary angiography revealed stenosis of one-to-three great coronary arteries
      and ventriculography showed no severe abnormalities in left ventricular
      contractility. A long-term drug therapy promoted not only improvement of the
      clinical status in most patients, but maintenance of work capacity and increase
      of their lifespan. The annual mortality rate was 3.0%, the incidence of nonfatal
      myocardial infarction was 5.9%. Repeated coronary angiography indicated that
      progression of coronary atherosclerosis was accompanied by a clinical
      deterioration in the patients' health and a decrease in exercise tolerance.

PMID- 1976849
TI  - [General, free and thrombocytic serotonin in the blood plasma of patients with
      hemorrhagic fever with renal syndrome].
AB  - The study determined the content of free, total and thrombocytic serotonin in 26
      patients suffering from hemorrhagic fever with renal syndrome (HFRS) varying in
      stage. Oligoanuria and polyuria periods of the disease were associated with a 5.5
      fold increase in the level of free serotonin whereas the level of blood platelet
      serotonin reduced two-fold and more. The convalescence period was characterized
      by rapid recovery of free serotonin values, thrombocytic serotonin being still
      insufficient. Peak values of total serotonin were noted in the polyuric period.

PMID- 1976848
TI  - [The prognostic significance of lymphocyte subpopulations and macrophages in
      peripheral blood and in bronchoalveolar lavage in AIDS patients with suspected
      Pneumocystis carinii pneumonia].
AB  - In 36 HIV seropositive patients with the clinical manifestation of AIDS and a
      suspected Pneumocystis carinii infection, lymphocyte subpopulations were analyzed
      in the peripheral blood (PBL) and compared with the results of the
      bronchoalveolar lavage (BAL). Of those 36 patients, 29 showed a highly abnormal
      CD4/CD8 ratio in both the PBL and the BAL. The clinical course of these 29
      patients was unpredictable. In seven patients, however, the CD4/CD8 ratio in the
      BAL was normal or only slightly altered, despite a highly abnormal CD4/CD8 ratio
      in the PBL. Five of these seven patients improved greatly during the clinical
      course. The positive outcome of the clinical course was even more strongly
      correlated with the number of macrophages in the BAL. Twelve of the 36 patients
      showed normal or only slightly changed numbers of macrophages in the BAL. Eleven
      of these twelve patients (92%) improved rapidly during antibiotic therapy, while
      the clinical course was unpredictable in patients with markedly reduced
      macrophage counts in the BAL.

PMID- 1976850
TI  - [Results of medical studies in relation to the program of the second space flight
      on the orbital complex "Mir"].
AB  - In 1987, the USSR cosmonauts Y. V. Romanenko (326 days), A. I. Laveikin
      (approximately 176 days), and A. P. Alexandrov (approximately 160 days) made a
      space mission on Mir. (A. I. Laveikin showed specific cardiovascular responses to
      exercise tests and was therefore replaced with A. P. Alexandrov). The most
      important medical result of this mission was that Yu. V. Romanenko, who remained
      in orbit for 3 months longer than anyone before, working intensively, did not
      exhibit any changes that were qualitatively different from those observed in
      previous long-duration space flights. The health status and work performance of
      other crewmembers were also good, although each of them showed individual
      responses. The postflight recovery period went smooth.

PMID- 1976852
TI  - Distribution of tyrosine hydroxylase (TH)-like, neuropeptide Y (NPY)-like
      immunoreactive and acetylcholinesterase (AChE)-positive nerve fibers in the
      prostate gland of the monkey (Macacus fuscatus).
AB  - Nerve fibers containing immunoreactivities for tyrosine hydroxylase (TH) and
      neuropeptide Y (NPY), and exhibiting acetylcholinesterase (AChE) reactivity were
      examined by means of histochemical and immunohistochemical methods in the caudal
      lobe of the prostate in the monkey, Macacus fuscatus. TH-like immunoreactive
      nerve fibers were distributed abundantly in the interstitium where smooth muscle
      fiber bundles were rich and scarcely in the paraurethral region where they were
      rare. NPY-like immunoreactive nerve fibers, less abundant than TH-like
      immunoreactive nerve fibers, were observed not only in the interstitium but also
      around the prostatic acini. AChE-positive nerve fibers were much denser around
      the acini than in the interstitium. Both the NPY-like immunoreactive and the AChE
      positive nerve fibers showed an intimate spatial association with the epithelium
      of the acini. Judging from the distribution pattern of these nerve fibers, the
      following assumption is possible. Secretion of the prostatic gland as well as the
      outflow of the prostatic fluid into the urethra induced by contraction of the
      smooth muscle cells in the interstitium may be controlled by sympathetic
      adrenergic nerves, while cellular secretion of the acinar epithelium is regulated
      by parasympathetic cholinergic nerves. The NPY-like immunoreactive nerve fibers
      around the acini may be non-noradrenergic; they may regulate the cellular
      secretion by acting on the cholinergic nerves as well as by having a direct
      effect on the acinar secretory cells.

PMID- 1976851
TI  - [The role of higher plants in the human biological life support system].
AB  - This paper discusses the functional characteristics of the man-plant
      mineralization system and the environment it forms when it is supplemented with a
      photoautotrophic component including higher plants and algae. The functional
      characteristics of the higher plant component were studied when it operated first
      in an independent cultivation mode, then coupled with a biological system of
      human and biocomplex waste mineralization, and finally with a human gas exchange
      system and Chlorella containing photosynthetic reactors. This approach
      demonstrated for the first time that Chlorella and higher plants can normally
      work in a common autosphere. The paper also presents quantitative data about the
      use of higher plants in a biological life support system. Data analysis shows
      that the total plant yield did not diminish when the system was closed and man,
      mineralization system and algal reactors were connected. However although the
      total photosynthetic productivity remained unchanged, the yield of useful crops
      decreased. This points to a complex nature of the above effects, the causes of
      which remain so far inexplicable and require further study.

PMID- 1976853
TI  - Ethanol-induced inhibition of testosterone biosynthesis in rat Leydig cells: role
      of L-glutamate and pyruvate.
AB  - The mechanisms by which ethanol (EtOH) inhibits testicular testosterone
      biosynthesis were studied with isolated rat Leydig cells in vitro comparing the
      effects of EtOH in six different culture media. The actual sites of inhibition by
      EtOH, identified by measuring the steroidogenic precursors, varied depending on
      the medium used. In Krebs-Ringer bicarbonate buffer, EtOH inhibited both the
      conversion of pregnenolone to progesterone and androstenedione to testosterone.
      In the pyruvate (Pyr) supplemented Dulbecco's Modified Eagle medium, the
      decreased progesterone concentrations in the presence of EtOH were reflected to
      all successive steroids 17-OH-progesterone, androstenedione and testosterone. The
      presence of L-glutamate (Glu) in the medium elevated testosterone production, but
      EtOH still inhibited the conversion of pregnenolone to progesterone, and also the
      androstenedione/testosterone ratio was elevated because of the decreased
      testosterone concentrations. In the presence of both Glu and Pyr in the medium
      the EtOH-induced decreases in the steroid concentrations were fully recovered in
      isolated Leydig cells. These results demonstrate that both Pyr and Glu
      supplementations are essential for the maintenance of maximal rate of
      testosterone synthesis in vitro in the presence of EtOH.

PMID- 1976854
TI  - Effect of prostaglandin E in multiple experimental models: V. Effect on
      tumor/host interaction.
AB  - Prostaglandin E (PGE) has long been incriminated as a cause of the
      immunosuppression seen in cancer patients and for the increased rates of tumor
      growth due to the impairment of the immunologic response to the tumor. We have
      investigated the effect of PGE on tumor-host interaction by utilizing a
      parenterally administered long-acting PGE derivative, 16,16-dimethyl
      prostaglandin E (dPGE). Administration of dPGE was found to decrease the rate of
      tumor growth but at a cost of decreasing tumor-free body mass. The dPGE did not
      alter resting metabolic rates but did alter some parts of brain dopamine
      metabolism and significantly decreased the serum level of multiple amino acids.
      In conclusion, elevated PGE levels may significantly alter metabolism in tumor
      patients.

PMID- 1976855
TI  - gamma-Glutamyltranspeptidase in rat bronchoalveolar lavage fluid as a probe of 4
      ipomeanol and alpha-naphthylthiourea-induced pneumotoxicity.
AB  - Bronchoalveolar lavage fluid analysis has gained popularity as a rapid in vivo
      screen to evaluate the toxicity of both systemic and inhaled pneumotoxicants and
      is used in addition to the more commonly evaluated pathologic changes. This study
      evaluated gamma-glutamyltranspeptidase (GGT) in the bronchoalveolar lavage fluid
      (BALF) along with the more commonly measured enzyme, lactate dehydrogenase (LDH),
      as a useful indicator of acute lung injury from systematically administered
      pneumotoxicants. Adult male rats were injected ip with 2, 3, or 3.5 mg/kg body
      weight of alpha-naphthylthiourea (ANTU) or 5, 10, or 20 mg/kg of 4-ipomeanol, and
      measurements were made 8 or 24 hr postdose, respectively. ANTU, which selectively
      damages pulmonary endothelial cells, caused extensive pleural effusions with
      striking increases in BALF protein and white blood cell (WBC) content. 4
      Ipomeanol, which selectively damages nonciliated bronchiolar Clara cells, caused
      dose dependent increases in both GGT and LDH activities in the BALF with GGT
      being increased at all doses tested. BALF protein content was also increased in
      the 4-ipomeanol-treated groups, but this change was not dose dependent. Analysis
      of GGT in BALF was a sensitive method to assess cytotoxicity associated with 4
      ipomeanol-induced injury but was less useful in monitoring pulmonary endothelial
      cell damage induced by ANTU. Measurements of BALF protein and WBC content proved
      to be better in assessing injury by agents such as ANTU that primarily affect
      vascular permeability.

PMID- 1976856
TI  - AIDS, other immunodeficiency disorders, and the lymphatic system:
      pathophysiology, diagnosis, and immunotherapy. XIIth International Congress of
      Lymphology. Tokyo Japan, August 30, 1989. Proceedings.

PMID- 1976857
TI  - [Insertion of a radius head prosthesis in the management of fresh injuries].
AB  - Authors report on experiences in using radius head prosthesis on the basis of
      early follow-ups. The operation is performed in cases of closed, comminuted
      fractures of the radial head if the fracture is irreponable on the basis of X-ray
      and intraoperative findings. Controls until now have shown excellent functional
      results. Based on literary data they describe the possibilities of late
      complications after using silicone prosthesis. The number of patients and the
      short time elapsed after operations does not allow far-reaching conclusions yet.
      A description of the use of radius head prosthesis in traumatology was not found
      in the Hungarian literature.

PMID- 1976858
TI  - [Lesions of the extensor muscles of the knee caused by meniscus injury].
AB  - The damage of the knee extensors was examined with integrated EMG and with
      histochemical and electron microscopical methods in 23 patients with meniscal
      injury. The integrated DMG has proved in 2/3 of the patients tonic, in 1/3 both
      tonic and phasic damage of the muscle function. With histochemical examination
      the decrease of the ratio of the fibers of type 1 was found and also the atrophy
      of the same fibre type cells in 18-36 per cent. Ultrastructural examinations have
      shown out of the damage of the contractive elements an increase of the
      interstitial connective tissue together with alterations of the arterioles in the
      knee extensors following meniscal injuries.

PMID- 1976860
TI  - [Injury of the rotator cuff. II. Diagnostic and therapeutic problems].
AB  - Authors examined the clinical problems of the rotator cuff injuries. The
      possibilities of the early diagnosis are reviewed and the significance of the
      detailed physical examination and of the shoulder arthrography stressed. The
      indication of the conservative and operative treatment is defined and also the
      optimal time of the reconstructive operation. In massive tears, in young age, the
      early diagnosis and the necessity of the urgent operations is stressed whereas in
      degenerative alterations, before the operative therapy of the cuff defects, in
      every case complex physiotherapeutic treatment is suggested. It is underlined
      that the operative results are improved by the good exposure, the possibly simple
      and reliable closure of the defect with a synchronous widening of the space under
      the shoulder vault. Because of the great variety of the injuries an individually
      chosen functional aftertreatment of many months is thought necessary.

PMID- 1976861
TI  - [Classification of polytraumatized patients, experience with the ISS system].
AB  - Authors assessed the process of healing of 161 polytraumatized patients from 1976
      to 1987, treated intersively, using the ISS system. Mortality was 27 per cent.
      Independently from the ISS system the concomittant shock foretold invariably a
      bad prognosis, although this was also joined generally to a big point number. The
      ISS system is simple and characterized the degree of the injury well. Through it,
      it will be possible to measure the gravity of the injury, to estimate
      statistically the prognosis and to compare the different materials. The number of
      points in the ISS system shows a good correlation with the survival (death) and
      the length of the intensive treatment. No patient was lost below 28 points
      whereas over 49 only 2 have survived. The point value may give information only
      up to the level of statistical probability concerning the prognosis (or the
      activity of the treatment) of the single patients. Because of its simplicity, its
      wide spreading and good practical use the general introduction of the ISS point
      system, as basic system, is thought to be advisable. For a more accurate judging
      a further making better and completing of the system (age, conjoined diseases,
      factors influencing each other mutually) further of the use, if necessary, of the
      scores applied in accident surgery and intensive therapy seems to be suggested.

PMID- 1976859
TI  - [Effect of adductor tenotomy on the hip joint in spastic paralysis].
AB  - Author examined the effect of adductor tenotomies in spastic patients. The
      changes of passive abduction, of the shaft-neck angle, of Wiberg's angle and of
      the decentric distance are evaluated following the operation. It was found that
      the change of the supplementary development of the acetabulum decreases with the
      time. With this operation the scissoring gait and the subluxation of the hip can
      be eliminated.

PMID- 1976862
TI  - [Experience with the Matti-Russe-Zolczer method in the surgical management of
      pseudoarthrosis of the navicular bone of the wrist].
AB  - Authors performed in the Department of Traumatology of the County Hospital
      Kaposvar from 1979 to 1985 22 Matti-Russe-Zolczer operations for pseudoarthrosis
      of the navicular bone. The necessity of the strict observance of the conditions
      of indication is stressed. The results of operations were assessed in a follow
      up. The time elapsed between the operation and control was 2 and 6 years. Good
      results were achieved after the use of Matti-Russe-Zolczer operation in 22
      patients with navicular pseudoarthrosis.

PMID- 1976863
TI  - [Conservative treatment of camptodactyly].
AB  - Authors describe their method used in the treatment of camptodactyly. After a 6
      year follow-up they report on good functional and esthetic result. In 1 case,
      even with a late therapy in 5 years of age, considerable improvement could the
      reached.

PMID- 1976864
TI  - [Fracture of the process of the scapula].
AB  - Authors call attention, describing 3 cases of their own, to the diagnostical
      difficulties of these rare injuries. They think the axillary Roentgenogram,
      except the dislocated fractures of the humerus, in all injuries of the shoulder
      region necessary. In 2 cases operations were performed, 1 patient was treated
      conservatively. In case of fracture of the process with impirtant dislocation
      operation is suggested. The patients healed with good functional results.

PMID- 1976867
TI  - [Management of pseudarthrosis of the olecranon].
AB  - Authors briefly summarized the classification, the causes and origin of the
      pseudoarthroses. The pseudoarthrosis of the olecranon may play an important role
      in the development of the disturbances of the movement in the elbow joint. In
      connection with 3 cases of their own the possibilities to restore the badly
      damaged joint and to eliminate function disturbances are demonstrated.

PMID- 1976866
TI  - [Closed injury of the pericardium].
AB  - The closed rupture of the pericardium without accompanying intrathoracal
      injuries, is a rare lesion. These cases are diagnosed generally at autopsy.
      Authors describe a case, successfully treated by operation.

PMID- 1976865
TI  - [CT follow up of the healing process in fractures of the talar corpus].
AB  - After reviewing the literary data on the frequency, the etiology, the
      classification and the anatomical characteristics of the talar fractures authors
      describe a healed case of a rarely occurring central talus fracture. The bony
      rebuilding was proven with CT. The importance of the early careful reduction, the
      performance of operation if necessary and the long lasting release of weight
      bearing are stressed, and the fact too that the CT, a noninvasive examination, is
      a valuable means in the judgement of bony rebuilding.

PMID- 1976868
TI  - [Complications of an incorrectly treated diaphyseal fracture of the humerus and
      corrective surgery leading to healing].
AB  - Author describes a case of a fracture in the upper third of the humerus in which
      a pseudoarthrosis developed in consequence of the insufficient fixation. After
      the second operation an osteosynthesis with a "spoon"-plate was performed
      together with transplantation of autologous cancellous bone. The lesson drawn
      from this case is analysed after healing.

PMID- 1976869
TI  - [Humeral fracture after keyhole tenodesis].
AB  - Author reports on experiences with the Froimson-Oh operation for rupture of the
      long head of the biceps brachii. The operation is thought to be advantageous. It
      is stressed in connection with 2 cases that the faulty choice of the place of the
      keyhole and its unadequate formation may predispose to humerus fracture and
      therefore this stage of the operation needs special care. The patient has to be
      warned, beside early movement, to adequate caution.

PMID- 1976870
TI  - Integrin distribution and cytoskeleton organization in normal and malignant
      monocytes.
AB  - In this work we have mapped by double-label immunofluorescence the cellular
      distribution of integrins and their relationship with cytoskeletal proteins in
      normal and malignant monocytes. In normal monocytes, CD18 and CD11c are
      concentrated at specific adhesion sites, named podosomes, together with actin,
      vinculin, and talin, while CD11a, CD11b, CD29/beta 1, CDw49d/alpha 4 and
      CD54/ICAM-1 retain a diffuse distribution on the cell surface without a selective
      pattern of localization. U-937 and fresh leukemic monoblasts under standard
      culture conditions do not adhere and do not form podosomes, but, when treated
      with TPA, they promptly adhere to substrate, form podosomes and focal adhesions
      in different cells and display the same integrin/cytoskeleton relationship as
      normal mature monocytes. Further, in these cells CD18, CD11a, CD11c, ICAM-1, and
      talin, but not vinculin, co-localize in homotypic cell junctions, thus showing a
      close relationship between integrins and talin. These observations provide
      morphological evidence that, in cells of the monocytic lineage, podosome
      formation is acquired upon differentiation and different integrins are
      selectively localized at different adhesion sites.

PMID- 1976872
TI  - Decrease in asparagine synthetase activity during cell differentiation of mouse
      and human leukemia cell lines.
AB  - The activity of asparagine synthetase decreased almost 50% during dexamethasone
      induced mouse myeloid leukemia M1 cell differentiation. This enzyme activity also
      declined significantly during differentiation of the human myelogenous leukemic
      cell lines, HL-60 and U-937, induced by either macrophage culture supernatant or
      retinoic acid. The decline of asparagine synthetase activity closely paralleled
      the expression of various maturation markers, but could also be induced by serum
      starvation. These results suggest that asparagine synthetase or L-asparagine has
      some biological function in growth regulation of these leukemia cell lines.

PMID- 1976871
TI  - The role of the MDR-1/P-170 mechanism in the development of multidrug resistance
      in chronic myeloid leukemia.
AB  - We studied blood and bone marrow cells from 42 patients with Ph-chromosome
      positive chronic myeloid leukemia (CML) and 20 normal subjects for amplification
      of the multidrug resistance gene (MDR-1) by Southern blotting and for
      overexpression of P-glycoprotein (P-170) by immunocytochemistry on intact cells
      with the monoclonal antibody C219. No P-170 could be detected in normal bone
      marrow or buffy coat. Overexpression of P-170 without amplification of MDR-1 was
      found in four of 11 patients with chronic phase CML at diagnosis, seven of 16
      patients treated with busulfan or hydroxyurea in chronic phase and four of 15
      patients in blast crisis. The P-170 overexpression involved only cells of the
      granulocyte lineage and varied from weak to strong in individual patients. It did
      not correlate with duration of or response to treatment during chronic phase. In
      transformation P-170 expression was seen in differentiated cells of the
      granulocyte lineage but not in blast cells, although three patients had been
      treated intensively with lipophilic and other cytotoxic drugs to which they had
      become resistant. We conclude that resistance to busulfan and hydroxyurea in
      chronic phase and resistance of blast cells to other cytotoxic drugs in
      transformation are not mediated primarily through the MDR-1/P-170 pathway.

PMID- 1976873
TI  - [Accidental hypothermia in a tetraplegic patient treated with bethanechol and
      alpha adrenergic receptor blocking agents].

PMID- 1976874
TI  - [Drugs should never replace the art of medicine].

PMID- 1976875
TI  - Risk of myocardial infarction and death during treatment with low dose aspirin
      and intravenous heparin in men with unstable coronary artery disease. The RISC
      Group.
AB  - 796 men with unstable coronary artery disease (unstable angina or non-Q-wave
      myocardial infarction [MI] ), were randomised to double-blind placebo-controlled
      treatment with oral aspirin 75 mg/day and/or 5 days of intermittent intravenous
      heparin. The risk of MI and death was reduced by aspirin. After 5 days the risk
      ratio was 0.43 (confidence intervals, 0.21-0.91), at 1 month 0.31 (0.18-0.53),
      and at 3 months 0.36 (0.23-0.57). Aspirin reduced event rate in non-Q-wave MI and
      unstable angina, independently of electrocardiographic abnormalities or
      concurrent drug therapy. Heparin had no significant influence on event rate,
      although the group treated with aspirin and heparin had the lowest number of
      events during the initial 5 days. Treatment had few side-effects and high patient
      compliance.

PMID- 1976876
TI  - Outbreak of diarrhoea due to Escherichia coli O111:B4 in schoolchildren and
      adults: association of Vi antigen-like reactivity.
AB  - During six days in November, 1987, 611 pupils (age range 7-19 years) and 39
      adults (23-57) at a school complex in southern Finland had diarrhoea due to
      Escherichia coli O111:B4. Diarrhoea developed in 137 other household members
      during the two weeks after the school outbreak. The source of the organism
      remains unknown. The outbreak strains, when incubated at 22 degrees C or exposed
      to ampicillin, lost the lipopolysaccharide O antigen and began to react with
      antisera against Salmonella typhi Vi antigen. The Vi antigen-like reactivity
      increased the adherence of the organisms to Hep-2 cells. These results indicate
      that E coli O111:B4, and possibly other enteropathogenic E coli strains, should
      be considered in the diagnosis of all diarrhoea cases and not only in infantile
      diarrhoea. Expression of Vi antigen in E coli may play a part in virulence by
      enhancing adherence to the intestinal epithelium.

PMID- 1976878
TI  - Arterial responses during migraine headache.
AB  - The superficial temporal artery has been thought to be the main focus of pain
      during migraine attacks, but its diameter has never been measured directly. The
      use of a new, high-resolution ultrasound machine to measure arterial size in 25
      migraine patients with unilateral head pain showed that the lumen was wider on
      the painful than on the non-painful side during a migraine attack. The diameters
      of both radial arteries and the temporal artery on the non-painful side were
      smaller during than between attacks. The generalised vasoconstriction was not
      shared by the temporal artery on the affected side, which suggests a local
      vasodilatory response. The findings suggest that cephalic arteries may play a
      role in migraine pathogenesis.

PMID- 1976877
TI  - Rapid detection and prenatal diagnosis of beta-thalassaemia: studies in Indian
      and Cypriot populations in the UK.
AB  - The application of the amplification refractory mutation system (ARMS) to the
      detection of individual beta-thalassaemia mutations in heterozygous parents and
      "at risk" fetuses has been assessed in Indian and Cypriot immigrant populations
      in the UK. 100 first trimester prenatal diagnoses have been done, entailing the
      detection of 17 different mutations. The method, which allows the determination
      of the mutations in both parental and fetal DNA on the same day, should have wide
      application to the carrier detection and prenatal diagnosis of monogenic diseases
      with heterogeneous molecular defects.

PMID- 1976880
TI  - Medical ethics: should medicine turn the other cheek?

PMID- 1976879
TI  - Disaster epidemiology.

PMID- 1976881
TI  - Medically assisted conception.

PMID- 1976882
TI  - Is clubbing a growth disorder?

PMID- 1976883
TI  - European experience of bone-marrow transplantation for severe combined
      immunodeficiency.
AB  - The outcome of bone-marrow transplantations (BMT) carried out between 1968 and
      March 1, 1989, in 183 patients with severe combined immunodeficiency (SCID) was
      analysed. Recipients of HLA-identical BMTs (70) had a 76% probability of survival
      (median follow-up 73 months). Of the 32 treated since 1983, 97% have been cured
      (median follow-up 41 months). This good prognosis was associated with rapid
      development of T and B cell function. HLA-non-identical, T-cell-depleted, BMT (n
      = 100) gave significantly lower survival (52%; median follow-up 47 months).
      Factors associated with poor prognosis were the presence of a lung infection
      before BMT, absence of a protected environment, and use of female donors for male
      recipients. Use of a conditioning regimen significantly increased the frequency
      of sustained engraftment (86% vs 50% for non-conditioned BMT) and resulted in
      more frequent engraftment of donor B lymphocytes and myeloid cells. Donor B-cell
      chimerism was strongly associated with the development of normal B-cell function.

PMID- 1976886
TI  - Sources of infection: food.

PMID- 1976884
TI  - Dry instant blood typing plate for bedside use.
AB  - A monoclonal antibody-derived, dry blood grouping plate, based upon the simple
      disaccharide, trehalose, is described that is indefinitely stable at room
      temperature and was found to have a 99.8% accuracy when tested against a standard
      semiautomated assay. This plate can be used by personnel with no specific
      training to check the recorded A,B,O, and Rhesus blood type of potential
      transfusion recipients in the field and at the bedside. Trehalose-based reagents
      may be important for bedside testing and in developing countries where
      refrigeration is unreliable.

PMID- 1976885
TI  - Veterinary sources of foodborne illness.

PMID- 1976887
TI  - America through the looking glass: 2, postgraduate education.

PMID- 1976889
TI  - Adverse reactions to monosulfiram.

PMID- 1976888
TI  - Epilepsy no longer a disease of the mind.

PMID- 1976890
TI  - P300 as a predictor of recovery from coma.

PMID- 1976891
TI  - Antimotility agents for paediatric use.

PMID- 1976892
TI  - Intra-articular morphine for pain after knee arthroscopy.

PMID- 1976893
TI  - Multicentre study of antenatal calyceal dilatation detected by ultrasound.

PMID- 1976894
TI  - Risks of antenatal ultrasound.

PMID- 1976895
TI  - Tumour imaging with labelled liposomes.

PMID- 1976896
TI  - Potentiation of hydrocortisone activity in skin by glycerrhetinic acid.

PMID- 1976897
TI  - Bacteraemias in HIV-positive patients.

PMID- 1976898
TI  - Resurgent gonorrhoea in homosexual men.

PMID- 1976900
TI  - Enhanced detection by PCR of hepatitis C virus RNA.

PMID- 1976899
TI  - Washing with 8 mol/l urea to correct false-positive anti-HCV results.

PMID- 1976902
TI  - Interatrial shunts and decompression sickness.

PMID- 1976904
TI  - Intraduodenal 'Gastrografin' injection against Taenia saginata infection.

PMID- 1976901
TI  - Renal artery stenosis and peripheral vascular disease.

PMID- 1976903
TI  - Fatal cowpox-like virus infection transmitted by cat.

PMID- 1976905
TI  - Giardiasis due to deliberate contamination of water supply.

PMID- 1976906
TI  - Aspergillus in pepper.

PMID- 1976907
TI  - Runway malaria.

PMID- 1976908
TI  - Acute compartment syndrome secondary to theophylline poisoning.

PMID- 1976909
TI  - Diagnosis of phaeochromocytoma.

PMID- 1976911
TI  - The second twin.

PMID- 1976910
TI  - Intracerebellar fatal haemorrhage after thrombolytic therapy of suspected non-Q
      wave myocardial infarction.

PMID- 1976912
TI  - Closure of MRC units.

PMID- 1976913
TI  - Electromagnetic fields: is there a danger?

PMID- 1976914
TI  - Shiley heart valves.

PMID- 1976915
TI  - Dangers of nebulisers.

PMID- 1976916
TI  - Delivery systems and doses of aerosolised drugs.

PMID- 1976917
TI  - Rupture of tubal pregnancy after transvaginal puncture.

PMID- 1976918
TI  - Dry-slide clinical chemistry.

PMID- 1976919
TI  - Cuff size and blood pressure.

PMID- 1976920
TI  - Risks of myeloid leukaemia in children treated for solid tumours.

PMID- 1976921
TI  - Flow cytometry for measurement of antibodies to spermatozoa in subfertile men.

PMID- 1976922
TI  - Aluminium deposition in bone after contamination of drinking water supply.

PMID- 1976923
TI  - Sleep apnoea and myocardial infarction.

PMID- 1976924
TI  - Cardiac biopsy in myocarditis.

PMID- 1976925
TI  - Intermittent nitrate transdermal therapy.

PMID- 1976926
TI  - Molecular genotyping to predict debrisoquine hydroxylation phenotype.

PMID- 1976927
TI  - Prediction of clinical relapse after bone-marrow transplantation by PCR for
      Philadelphia-positive acute lymphoblastic leukaemia.

PMID- 1976928
TI  - Comparison of enteric-coated capsules and liquid formulation of Ty21a typhoid
      vaccine in randomised controlled field trial.
AB  - In a randomised, double-blind, controlled field trial in Santiago, Chile, 81,621
      schoolchildren aged 5-19 years received three doses, within a week, of attenuated
      Salmonella typhi oral vaccine Ty21a in enteric-coated capsules or in a new liquid
      suspension, or placebo. Over 36 months of surveillance, the liquid formulation
      (76.9% vaccine efficacy) was significantly superior to the enteric-coated
      capsules (33.2% vaccine efficacy). The liquid formulation protected young
      children (5-9 years) (efficacy 82.3%) as well as older children (efficacy 69.3%),
      whereas the capsules significantly protected only older children. The liquid
      suspension was easy to prepare by mixing lyophilised vaccine with buffer in water
      and was easily administered, even to the youngest children. Thus, the liquid
      formulation of Ty21a is preferable to enteric-coated capsules.

PMID- 1976929
TI  - Measurement of airborne mite antigen in homes of asthmatic children.
AB  - The airborne concentration of major house dust mite antigen Der p1 was measured
      by low volume sampling (2 litres/min) in the homes of 68 allergic, asthmatic
      children. The presence of detectable airborne antigen was strongly associated
      with sensitivity to the mite, whereas there was no significant relation between
      sensitivity and the previously recommended threshold level of 2 micrograms Der p1
      per g carpet dust. There was a significant association with lower threshold
      levels in carpet dust (0.5 microgram/g) but at no level was the association as
      strong as that with air measurements. Concentrations of airborne antigen were
      higher in rooms with wool carpets than in those with synthetic carpets or hard
      floors, but there was no significant difference between the dust levels of Der p1
      in the two carpet types. Air sampling is a more appropriate method of assessing
      antigen exposure than dust sampling for asthmatic patients.

PMID- 1976931
TI  - Preliminary report: complement activation in wasp-sting anaphylaxis.
AB  - The generation of the anaphylatoxin C3a was measured after a wasp-sting challenge
      in eight patients with previous anaphylactic reactions to wasp stings. Whereas
      there was no change in C3a in one patient who showed no reaction and only a
      slight rise in three patients with mild reactions, C3a rose substantially in the
      four patients with severe anaphylactic reactions. This complement activation is
      the first in-vitro variable which correlates with the severity of wasp-sting
      anaphylactic reactions. A role for complement activation in the pathophysiology
      of wasp-sting anaphylaxis is therefore suggested.

PMID- 1976930
TI  - Inhibitory effect of sandostatin on secretion of luteinising hormone and ovarian
      steroids in polycystic ovary syndrome.
AB  - Hyperinsulinism accompanies the raised luteinising hormone (LH) concentrations in
      women with the polycystic ovary syndrome (PCOS). Somatostatin inhibits insulin
      and LH secretion in healthy adults, so the effect of treatment with a long-acting
      somatostatin analogue ('Sandostatin') on gonadotropin and androgen secretion in
      PCOS was investigated. LH pulsatility, androgen concentrations, and hormonal
      responses to an oral glucose load and to administration of a GnRH agonist
      (buserelin) were measured before and after 7 days' treatment with sandostatin 100
      micrograms subcutaneously twice a day in 10 amenorrhoeic women with classic
      features of PCOS. Sandostatin significantly reduced integrated LH concentrations
      and LH pulse amplitudes, oestradiol, testosterone, and androstenedione
      concentrations, and LH responses to buserelin; it also suppressed insulin and C
      peptide responses to an oral glucose load. Thus sandostatin inhibits pituitary
      and ovarian hormonal responses in part by a direct influence on pituitary
      activity, and the possibility of an indirect effect mediated by changes in
      insulin concentrations requires investigation. These findings have implications
      for the treatment of infertility in women with PCOS.

PMID- 1976933
TI  - Mental health services for migrants in Europe.

PMID- 1976932
TI  - All aboard for octreotide.

PMID- 1976934
TI  - Korsakoff's syndrome.

PMID- 1976935
TI  - Treatment of oral lichen planus.

PMID- 1976936
TI  - Scalpel and seaweed, nurse.

PMID- 1976937
TI  - Specialist versus general practitioner treatment of problem drinkers.
AB  - The efficacy of specialist versus general practitioner (GP) treatment of problem
      drinkers was assessed in a randomised controlled trial. 40 problem drinkers
      referred consecutively to a specialist alcohol clinic by their GP were, after
      assessment, randomly allocated to either GP or specialist clinic treatment
      groups. All subjects received initial advice and counselling in the clinic about
      their drinking. The specialist clinic group received continued care from the
      clinic including, if necessary, admission to hospital. Patients in the GP group
      were returned to the care of the GP who was contacted and supported by the
      specialist. After 6 months of follow-up, there were significant reductions in
      alcohol consumption and alcohol-related problems in both groups. No significant
      difference was found between the two groups with respect to the main outcome
      measures. No differential treatment effect was found with the more severely
      dependent drinkers. The findings show that after an initial detailed assessment
      and advice session, the treatment provided by GPs is at least as effective as
      that from a specialist clinic with respect to improvements in drinking behaviour
      and alcohol-related problems. After initial assessment and advice, specialist
      clinics should encourage GPs to become more involved in the subsequent care of
      problem drinkers. Such a practice should be based on the individual patient's
      needs and the adequacy of support offered to GPs.

PMID- 1976938
TI  - Controlled evaluation of slimming diets: use of television for recruitment.
AB  - 352 overweight men and women took part in a six-week controlled trial of seven
      slimming regimens versus a placebo diet. They were recruited through a popular
      television programme. The findings showed that three regimens ('Bai-Lin Tea', the
      'Grapefruit Pill', and the 'Natural Vitality' pill) were ineffective. Reduction
      in energy intake either by meal replacement or by dietary modification led to
      successful weight loss. Commercial slimming clubs were the most effective
      measures. Television and other media could be used to test other hypotheses with
      randomisation experiments.

PMID- 1976939
TI  - Campylobacter.

PMID- 1976940
TI  - Ecology, life cycle, and infectious propagule of Cryptococcus neoformans.
AB  - Cryptococcus neoformans is a biotrophic smut-like fungus, and the epidemiology of
      cryptococcosis can mainly be explained by exposure to an infective aerosolised
      inoculum. For C neoformans var gattii it is postulated that the principal
      infectious propagule is the basidiospore and that exposure to Eucalyptus
      camaldulensis, the host tree, is required to initiate infection in man and
      animals. C neoformans var gattii may have been exported from Australia by
      infected seeds of E camaldulensis containing dormant dikaryotic mycelium of the
      fungus. For C neoformans var neoformans both the basidiospore and desiccated
      encapsulated yeast cells are postulated to act as infectious propagules, the
      basidiospores showing a seasonal distribution in association with an as yet
      unidentified host plant, and the encapsulated yeast cells dispersed from
      accumulations of dried bird (mainly pigeon) droppings which act as a year-round
      vector.

PMID- 1976941
TI  - America through the looking glass: 3, teaching, research, and service.

PMID- 1976942
TI  - A cryptic announcement clouds the Gallo case.

PMID- 1976944
TI  - WHO on low-dose oral interferon-alpha for AIDS.

PMID- 1976943
TI  - Trends in obstetric malpractice claims.

PMID- 1976945
TI  - Overpopulation and death in childhood.

PMID- 1976946
TI  - Actinomycosis and long-term use of intrauterine devices.

PMID- 1976947
TI  - Pneumonia and community health workers.

PMID- 1976948
TI  - Community-acquired pneumonia in drug abusers in Amsterdam.

PMID- 1976949
TI  - Left ventricular mass and left ventricular diastolic function.

PMID- 1976951
TI  - Preferential replication of HIV-1 in memory CD4+ subpopulation.

PMID- 1976950
TI  - In-vitro production of HIV-1-specific antibody for diagnosis of perinatal
      infection.

PMID- 1976952
TI  - Breastfeeding and urinary-tract infection.

PMID- 1976953
TI  - New subtype of HIV-1 in Ethiopia.

PMID- 1976954
TI  - Protective foods.

PMID- 1976955
TI  - Anaphylaxis to glafenine.

PMID- 1976957
TI  - Publicity and controversial data.

PMID- 1976956
TI  - Ascorbic-acid-induced haemolysis in G-6-PD deficiency.

PMID- 1976958
TI  - Infectious aetiology of childhood leukaemia.

PMID- 1976959
TI  - Toxicity of D-lactate.

PMID- 1976960
TI  - Pseudomembranous colitis associated with ciprofloxacin.

PMID- 1976961
TI  - Transient postpartum hypothyroidism caused by thyroid-stimulation-blocking
      antibody.

PMID- 1976962
TI  - False-positive identification of Escherichia coli O157 by commercial latex
      agglutination tests.

PMID- 1976963
TI  - Corticosteroids and post-herpetic neuralgia.

PMID- 1976964
TI  - Fluvoxamine and epilepsy.

PMID- 1976965
TI  - Surfactant for adults with respiratory failure.

PMID- 1976966
TI  - Acetylcysteine in paracetamol poisoning.

PMID- 1976967
TI  - Neurological deterioration in young adults with phenylketonuria.

PMID- 1976968
TI  - Phyllanthus amarus and hepatitis B.

PMID- 1976969
TI  - Hypoglycaemia and cerebral malaria.

PMID- 1976970
TI  - Beta 2-glycoprotein I for binding of anticardiolipin antibodies to cardiolipin.

PMID- 1976971
TI  - Rectal gluten challenge and diagnosis of coeliac disease.

PMID- 1976972
TI  - Enhancement of recovery from psychiatric illness by methylfolate.

PMID- 1976973
TI  - Flat seats for convex bottoms.

PMID- 1976974
TI  - Homoeopathic treatment of fibrositis.

PMID- 1976975
TI  - Relation between serum cholesterol and diabetic nephropathy.

PMID- 1976976
TI  - Beta-blockers for preventing variceal bleeding.

PMID- 1976977
TI  - Anisakis simplex, a co-factor of gastric cancer?

PMID- 1976978
TI  - Living non-related kidney transplantation in Bombay.

PMID- 1976979
TI  - Compliance and clinical trials in heart disease.

PMID- 1976980
TI  - Tissue platinum concentrations and cisplatin schedules.

PMID- 1976981
TI  - Capsaicin for treatment of post-traumatic amputation stump pain.

PMID- 1976982
TI  - Listeria, plasmids, antibiotic resistance, and food.

PMID- 1976983
TI  - Combination diuretic therapy for severe refractory nephrotic syndrome.

PMID- 1976984
TI  - Adverse reactions in expatriates treated with ivermectin.

PMID- 1976985
TI  - Ethnic distribution of beta-thalassaemia in Indian subcontinent.

PMID- 1976986
TI  - Evaluation of WHO/CDC clinical criteria for diagnosis of AIDS in Cameroon.

PMID- 1976987
TI  - Monoclonal CD4 antibodies after accidental HIV infection.

PMID- 1976989
TI  - Condom use and failure.

PMID- 1976988
TI  - Confirmation of non-infection in persistently HIV-seronegative recipients of
      contaminated factor VIII.

PMID- 1976990
TI  - Orally operated mucus extractors made safe.

PMID- 1976991
TI  - Use of oral rehydration salt in diabetic ketoacidosis.

PMID- 1976992
TI  - Mianserin and agranulocytosis.

PMID- 1976993
TI  - Toxic epidermal necrolysis due to paediatric erythromycin/sulfisoxazole
      combination.

PMID- 1976994
TI  - 21-day cycles of oral etoposide in heavily pretreated metastatic germ-cell
      cancer.

PMID- 1976995
TI  - Assisted death.

PMID- 1976996
TI  - Medical care for Palestinians.

PMID- 1976997
TI  - Safety of hysteroscopic surgery.

PMID- 1976998
TI  - Raynaud's phenomenon, calcitonin gene-related peptide, endothelin, and cutaneous
      vasculature.

PMID- 1976999
TI  - Tumour-necrosis factor in normal plasma.

PMID- 1977000
TI  - Eosinophilia-myalgia syndrome, L-tryptophan, and informed consent.

PMID- 1977001
TI  - Preventing congenital toxoplasmosis.

PMID- 1977002
TI  - Contraceptive efficacy of testosterone-induced azoospermia in normal men. World
      Health Organization Task Force on methods for the regulation of male fertility.
AB  - A multicentre study (ten centres) in seven countries was done to assess the
      contraceptive efficacy of hormonally-induced azoospermia in 271 healthy fertile
      men. Each subject received 200 mg testosterone enanthate weekly by intramuscular
      injection. 157 men (cumulative rate at 6 months 65%) became azoospermic in three
      consecutive semen samples. These men entered a 12-month efficacy phase during
      which continuing testosterone injections were the only form of contraception.
      There was 1 pregnancy during 1486 months of the efficacy phase (0.8 conceptions
      [95% confidence interval 0.02-4.5] per 100 person-years). Discontinuations from
      the study were mainly because azoospermia was not achieved within 6 months and
      because of dislike of the injection schedule. The mean time to become azoospermic
      was 120 days (SD 40); reappearance of spermatozoa was detected in 11 men and in
      no case led to discontinuation from the study or to pregnancy. After the
      testosterone injections had been stopped, the estimated median time from
      azoospermia to recovery (sperm concentration of at least 20 million/ml) was 3.7
      months (3.6-3.9) and to the subject's mean baseline sperm concentration was 6.7
      months (6.2-8.7). Hormonal regimens that induce azoospermia can provide highly
      effective, sustained, and reversible male contraception with minimum side
      effects.

PMID- 1977003
TI  - Chlamydia trachomatis in the fallopian tubes of women without laparoscopic
      evidence of salpingitis.
AB  - 23 women with lower abdominal pain and Chlamydia trachomatis in the cervix,
      urethra, or both sites were studied. Laparoscopy was done with sampling of the
      endometrium and fallopian tubes for detection of C trachomatis. 11 women had
      laparoscopic evidence of pelvic inflammatory disease (PID); C trachomatis was
      detected in the upper genital tract of 8, but not in the upper tract of 5 who had
      laparoscopy again after treatment. The organism was also found in the upper
      genital tract of 9 of the 12 women without laparoscopic evidence of PID. Most of
      the women with abdominal pain or tenderness had tubal or endometrial C
      trachomatis infection, although only half had laparoscopic evidence of
      salpingitis. This finding suggests that antibiotic treatment should be given as
      soon as chlamydial infection is detected in the cervix and that pain does not
      necessarily point to C trachomatis in the upper genital tract. Laparoscopy may
      miss important pathogens in the upper genital tract, unless the procedure is
      complemented with detailed microbiological investigation.

PMID- 1977004
TI  - Evoked potentials in assessment and follow-up of patients with Wilson's disease.
AB  - Treatment of 9 patients with Wilson's disease was prospectively studied with
      evoked potentials and magnetic resonance imaging (MRI). Oral penicillamine
      therapy led to a decrease in auditory brainstem (ABP) and somatosensory (SEP)
      conduction times in 6 and 4 neurologically symptomatic patients, respectively.
      ABP and SEP were normal in 3 other symptom-free patients. MRI showed cerebral
      lesions in 4 of 7 patients. Quantified indices of brain atrophy were unaffected
      by treatment. ABP and SEP may reveal a reversible component of the disease that
      cannot be detected by MRI, and may be a more sensitive measure of treatment
      efficacy.

PMID- 1977005
TI  - Antenatal intervention for congenital cystic adenomatoid malformation.
AB  - In 2 fetuses with congenital cystic adenomatoid malformation (CCAM) with hydrops,
      in-utero resection of the enlarged pulmonary lobe reduced mediastinal shift and
      allowed expansion of normal lung tissue in both cases. In case 1, the 27-week
      gestation fetus died from severe hydrops after premature delivery. In case 2,
      fetal CCAM resection was completed at 23 weeks' gestation. At 30 weeks a girl was
      delivered with no evidence of pulmonary hypoplasia. Fetal surgery can now be
      entertained for otherwise fatal space-occupying intrathoracic lesions.

PMID- 1977006
TI  - Hypothesis: is lung disease after silicate inhalation caused by oxidant
      generation?
AB  - Inhaled silicate dusts may cause lung disease through their surface coordination
      of iron with subsequent oxidant generation via the Fenton reaction.
      Pneumoconiosis, irritant bronchitis, focal emphysema, and carcinoma may be
      produced by oxidants either directly through lipid peroxidation and protein
      inactivation, or indirectly by oxidant-mediated release of cytokines such as
      platelet-derived growth factor. The increased incidence of tuberculosis observed
      among silicate workers could be explained by accumulation of iron complexed by
      dust particles in the lung and made available to dormant mycobacteria as a
      virulence factor.

PMID- 1977007
TI  - Dilated cardiomyopathy and enteroviruses.

PMID- 1977008
TI  - Fibrillin and Marfan's syndrome: a real clue?

PMID- 1977009
TI  - Hastening gut transit.

PMID- 1977010
TI  - On bedresting in heart failure.

PMID- 1977011
TI  - Carbon fibres and hernia repair.

PMID- 1977012
TI  - Laryngeal mask airway and tracheal tube insertion by unskilled personnel.
AB  - After a short training programme 11 naval medical trainees inserted a laryngeal
      mask airway (LMA) and a tracheal tube (ETT) in random order in a total of 110
      anaesthetised patients. They were allowed 40 s for each attempt. Success was
      defined as the detection of expired carbon dioxide within 40 s of Guedel airway
      removal which subsequently rose to an end-tidal value of at least 4 kPa, together
      with satisfactory lung expansion and ventilation, without other airway
      intervention by the anaesthetist. 104 LMA insertions were successful compared
      with 56 of ETTs (p less than 0.01). All first attempts at LMA insertion were
      successful, whereas satisfactory ETT placement was progressive. Insertion was
      also quicker with the LMA (20 s) than with the ETT (35 s) (p less than 0.01).
      Further studies are indicated to assess the value of the LMA in emergencies.

PMID- 1977013
TI  - Fetal platelet counts in thrombocytopenic pregnancy.
AB  - Fetal platelet counts were assessed by percutaneous umbilical blood sampling in
      64 pregnancies (62 women) with maternal thrombocytopenia. In 33 pregnancies
      associated with chronic immune thrombocytopenia, 11 of the fetuses had platelet
      counts below 150 x 10(9)/l and 4 were severely thrombocytopenic (less than 50 x
      10(9)/l). In 31 pregnancies with symptomless maternal thrombocytopenia as an
      incidental finding, 4 fetuses were thrombocytopenic, 1 of them severely. Maternal
      indices, including antiplatelet antibodies, did not correlate with risk of fetal
      thrombocytopenia; and in those with repeat measurements there was no evidence of
      benefit from treatment with either corticosteroids (4 cases) or intravenous
      immunoglobulin (3 cases). Percutaneous umbilical blood sampling, a safe procedure
      in experienced hands, provides accurate platelet counts in thrombocytopenic
      pregnancy, as an aid to decisions on mode of delivery and to assessment of
      treatments.

PMID- 1977014
TI  - Foodborne disease due to Bacillus and Clostridium species.

PMID- 1977015
TI  - Adult T-cell leukaemia/lymphoma in Brazil and its relation to HTLV-I.
AB  - In a series of fourteen patients with adult T-cell lymphoma-leukaemia (ATLL) in
      Brazil the main features were lymphadenopathy, hepatosplenomegaly,
      hypercalcaemia, and high leucocyte counts, with abnormal lymphoid cells which had
      irregular nuclei. The series included the youngest patient with ATLL so far (18
      months). Analysis with monoclonal antibodies showed a mature T-cell phenotype
      (CD4+, CD8-). Antibodies to HTLV-I and/or integration of HTLV-I proviral DNA were
      found in eleven patients. In the other three HTLV-I DNA could not be demonstrated
      even by means of the polymerase chain reaction; they therefore had HTLV-I
      negative ATLL. This report of ATLL in Brazil corroborates serological reports
      that HTLV-I may be endemic in some parts of that country. Follow-up studies are
      required to identify precisely the main route of transmission of HTLV-I in South
      America and the risk factors for the development of ATLL in carriers.

PMID- 1977016
TI  - Product liability proposals, Sweden.

PMID- 1977017
TI  - Demonstration of viraemia patterns in haemophiliacs treated with hepatitis-C
      virus-contaminated factor VIII concentrates.
AB  - Sequential serum samples from previously untreated haemophiliacs in whom non-A,
      non-B hepatitis (NANBH) developed after they received factor VIII concentrate
      contaminated with hepatitis C virus (HCV) were tested by a commercial assay for
      the presence of antibodies to the C100 protein of HCV (anti-C100) and by "nested"
      PCR for the presence of HCV RNA sequences. Three temporal patterns of viraemia
      were observed: transient viraemia in acute resolving NANBH; viraemia lasting for
      several years in chronic NANBH; and intermittent viraemia in chronic NANBH, with
      an initial transient phase followed by recurrence after many months. In three of
      five cases the initial detection of serum HCV RNA was made before the onset of
      liver function test abnormality, many weeks or months before anti-C100
      seroconversion. Diagnosis of acute HCV infection may therefore be possible much
      earlier by PCR than by existing serological techniques, but the timing of samples
      may be critical.

PMID- 1977018
TI  - Non-inherited maternal HLA antigens and protection against sensitisation.
AB  - To test the hypothesis that non-inherited maternal antigens (NIMAs), which
      reportedly afford protection against sensitisation by random transfusions, can
      provide protection against repetitive antigenic exposure of donor-specific
      transfusion (DST), 140 DST patients whose donors were mismatched for NIMAs and 71
      whose donors were mismatched for non-inherited paternal antigens (NIPAs) were
      studied. The rate of sensitisation in the two groups of patients was similar
      (22.1% vs 15.5%). There was no difference in sensitisation to NIMAs and NIPAs
      between patients who received azathioprine and those who did not. The formation
      of donor specific HLA antibody was comparable in the two groups. After kidney
      transplantation there were no differences in 1-year graft survival or the
      incidence of rejection episodes. These findings suggest that NIMAs do not provide
      lifelong protection against subsequent repetitive antigen challenge and
      sensitisation.

PMID- 1977019
TI  - Preliminary report: activation of the cerebellum in essential tremor.
AB  - Several images of cerebral blood flow were recorded during inhalation of carbon
      15-labelled carbon dioxide by positron emission tomography in four patients with
      essential tremor and four normal controls. Unilateral involuntary postural tremor
      in essential tremor patients was associated with blood flow significantly greater
      than that at rest in the contralateral sensorimotor cortex, both lateral premotor
      regions, and both cerebellar hemispheres. Of these regions, only the cerebellum
      was not activated in normal controls holding a posture without tremor or in
      essential tremor patients undergoing passive wrist movement. The increased flow
      in the cerebellum therefore seems to represent neural activity involved in tremor
      generation. It is proposed that essential tremor is due to oscillation within
      cerebello-olivary pathways, relayed by way of the thalamus and motor cortex to
      the spinal cord.

PMID- 1977020
TI  - Hypothesis: inhibition of endothelium-derived relaxing factor by haemoglobin in
      the pathogenesis of pre-eclampsia.
AB  - Although the aetiology of pre-eclampsia is unknown, haemodynamic studies suggest
      that many of the clinical findings may be explained by a generalised
      vasoconstrictive disorder and abnormal endothelial cell function.
      Vasoconstriction may be attributed to the increased concentrations of haemoglobin
      found in pre-eclampsia compared with normal pregnancy. Free haemoglobin may be
      derived from haemolysis and placental haemorrhage and, at concentrations known to
      be present in pre-eclampsia, vasodilatation mediated by endothelium-derived
      relaxing factor is inhibited. Infusion of oxyhaemoglobin into human coronary
      arteries inhibits acetylcholine-induced vasodilatation. We suggest that an
      increased free haemoglobin concentration is the cause of vasoconstriction in pre
      eclampsia.

PMID- 1977021
TI  - What causes motoneuron disease?

PMID- 1977022
TI  - Epilepsy and disorders of neuronal migration.

PMID- 1977023
TI  - Europe (against) for cancer.

PMID- 1977024
TI  - Perforin and leucocyte cytotoxicity in man.

PMID- 1977025
TI  - Doing better, feeling worse.

PMID- 1977026
TI  - Global scale of avoidable blindness.

PMID- 1977028
TI  - Foodborne staphylococcal illness.

PMID- 1977027
TI  - Neurological sequelae of cerebral malaria in children.
AB  - Out of 604 Gambian children admitted with falciparum malaria to one hospital
      between September and December, 1988, 308 had cerebral malaria and 203 were
      severely anaemic (haemoglobin less than 60 g/l). 14% of those with cerebral
      malaria died, as did 7.8% of those with severe anaemia. 32 (12%) of children
      surviving cerebral malaria had residual neurological deficit. 69 other children
      were admitted with clinical features strongly suggestive of cerebral malaria but
      with negative blood films; 16 of these died and 3 had residual neurological
      deficits. The commonest sequelae of cerebral malaria were hemiplegia (23 cases),
      cortical blindness (11), aphasia (9), and ataxia (6). Factors predisposing to
      sequelae included prolonged coma, protracted convulsions, severe anaemia, and a
      biphasic clinical course characterised by recovery of consciousness followed by
      recurrent convulsions and coma. At follow up 1-6 months later over half these
      children had made a full recovery, but a quarter were left with a major residual
      neurological deficit. Cerebral malaria in childhood may be an important cause of
      neurological handicap in the tropics.

PMID- 1977029
TI  - Antibody persistence in Gambian children after high-dose Edmonston-Zagreb measles
      vaccine.
AB  - Measles antibody concentrations in Gambian children immunised at 4 months of age
      with a high-dose Edmonston-Zagreb (EZ) measles vaccine or at 9 months with
      conventional Schwarz vaccine were measured 5 months after vaccination, and at 18
      and 36 months of age. Schwarz vaccinees produced, on average, a 2.4-fold higher
      concentration of measles haemagglutinin inhibiting (HAI) antibody than EZ
      vaccinees, but at 36 months of age 82 of 93 (88%) EZ vaccinees and 83 of 87 (95%)
      Schwarz vaccinees had measles plaque-neutralising antibody concentrations above
      the assumed protective level of 200 mIU/ml (p greater than 0.1). HAI antibody
      concentrations 5 months after vaccination were inversely related to the presence
      of maternal antibody at vaccination, but above protective levels; at 18 and 36
      months of age there was no relation to antibody concentration at vaccination, and
      decay of HAI antibody between 18 and 36 months of age was similar for EZ and
      Schwarz vaccinees.

PMID- 1977030
TI  - Evaluation of prevalence of "doping" among Italian athletes.
AB  - To evaluate knowledge of, attitudes to, and use of illegal drugs and other forms
      of "doping" in sport 1015 Italian athletes and 216 coaches, doctors, and managers
      (technicians) were interviewed after selection on a quota basis. Overall, 30% of
      athletes, managers, and coaches and 21% of doctors indicated that athletic
      performance can be enhanced by drugs or other doping practices. Over 10% of
      athletes indicated a frequent use of amphetamines or anabolic steroids at
      national or international level, fewer athletes mentioning blood doping (7%) and
      beta-blockers (2%) or other classes of drugs. These proportions were 2-3 times
      higher for occasional use than for frequent use. Estimates by managers and
      coaches were much the same as those of athletes when allowance was made for
      larger random variation. 62% of athletes who acknowledged doping reported
      pressure to do so from coaches and managers. According to over 70% of athletes
      access to illegal substances was not difficult. Both athletes and technicians
      awarded higher scores to risk than to efficacy for any substance, although 42-67%
      of athletes and technicians regarded amphetamines and anabolic steroids as
      efficacious. 82% wanted stricter controls not only during competitions but also
      during training.

PMID- 1977031
TI  - Tissue pressure, posture, and venous ulceration.

PMID- 1977032
TI  - In my beginning is my end.

PMID- 1977033
TI  - Detention without trial.

PMID- 1977034
TI  - Spread of multiresistant Salmonella typhi.

PMID- 1977035
TI  - Prevention of Pneumocystis carinii pneumonitis in AIDS patients with weekly
      dapsone.

PMID- 1977036
TI  - Possible transfer of Pneumocystis carinii between kidney transplant recipients.

PMID- 1977037
TI  - Infection of human T cells with mycoplasma, inhibition of CD4 expression and HIV
      1 gp120 glycoprotein binding, and infectivity.

PMID- 1977038
TI  - Cyclophosphamide versus ifosfamide in paediatric oncology.

PMID- 1977039
TI  - Fetal response to maternal shock.

PMID- 1977040
TI  - Herbs and hepatitis.

PMID- 1977041
TI  - Aspirin and prevention of myocardial infarction.

PMID- 1977042
TI  - Enrolment in trials of thrombolysis.

PMID- 1977043
TI  - Decrease of HTLV-I infection in haemodialysis patients after donor screening.

PMID- 1977044
TI  - Perinatal adverse effects of nalbuphine given during labour.

PMID- 1977045
TI  - Low risk from feline cowpox.

PMID- 1977046
TI  - Dengue-2 virus in Kenya.

PMID- 1977047
TI  - Serological evidence of reinfection among vaccinees during rubella outbreak.

PMID- 1977048
TI  - Right-to-left shunt and neurological decompression sickness in divers.

PMID- 1977049
TI  - Clinical signs in neonatal pneumonia.

PMID- 1977050
TI  - Endogenous prostaglandins as regulators of cell proliferation.

PMID- 1977052
TI  - Medical ethics.

PMID- 1977051
TI  - Failure to thrive.

PMID- 1977053
TI  - Risk taking in general practice.

PMID- 1977054
TI  - Homelessness after discharge from psychiatric hospitals.

PMID- 1977055
TI  - Jhatka and halal meat.

PMID- 1977056
TI  - Jehovah's Witnesses with leukaemia.

PMID- 1977057
TI  - Possible linkage of Tourette syndrome to markers on short arm of chromosome 3
      (C3p21-14)

PMID- 1977058
TI  - Benzene in petrol: a continuing hazard.

PMID- 1977059
TI  - Lack of association between raised serum Lp(a) concentration and unsuccessful
      thrombolysis after acute myocardial infarction.

PMID- 1977060
TI  - Fatal effect of re-exposure to heparin after previous heparin-associated
      thrombocytopenia and thrombosis.

PMID- 1977061
TI  - Effect of combination chemotherapy with verapamil.

PMID- 1977062
TI  - Megadose methylprednisolone for chronic idiopathic thrombocytopenic purpura.

PMID- 1977063
TI  - Cardiogenic shock associated with verapamil in a patient with liver cirrhosis.

PMID- 1977064
TI  - Erythromycin-induced hearing loss.

PMID- 1977065
TI  - Is there an ideal distribution of adipose tissue?

PMID- 1977066
TI  - D-2 receptor-mediated inhibition by a substituted quinolinone derivative, 7-[3-(4
      (2,3-dimethylphenyl)piperazinyl)propoxy]-2(1H)-quinolinone (OPC-4392), of
      dopaminergic neurons in the ventral tegmental area.
AB  - A microiontophoretic study was performed to investigate the effects of a newly
      synthesized quinolinone derivative, 7-[3-(4-(2,3-dimethylphenyl) piperazinyl)
      propoxy] 2-(1H)-quinolinone (OPC-4392), on neuronal activities of the ventral
      tegmental area (VTA) of rats anesthetized with chloral hydrate. The VTA neurons,
      which were identified by antidromic stimulation of the nucleus accumbens (Acc),
      were classified into type I and type II neurons according to the responses to Acc
      stimulation: type I neurons had a long spike latency of over 7 msec (9.63 +/-
      0.25 msec), and the type II, a short latency of less than 7 msec (2.98 +/- 0.27
      msec) upon Acc stimulation. In all of 11 type I neurons, iontophoretically
      applied OPC-4392 and dopamine inhibited the antidromic spikes elicited by Acc
      stimulation. This inhibition was antagonized by simultaneous application of
      domperidone (dopamine D-2 antagonist). However, in 16 out of 19 type II neurons
      the antidromic spikes were not affected by either OPC-4392 or dopamine. When the
      effects of iontophoretically applied OPC-4392 and dopamine on spontaneous firings
      were tested in 32 VTA neurons identified by Acc stimulation (including type I and
      type II neurons), there was a relationship between the effects of these two
      drugs. These results suggest that OPC-4392 acts on dopamine D-2 receptors of the
      dopaminergic neurons in the VTA, thereby inhibiting neuronal activity.

PMID- 1977068
TI  - Oral complications associated with endotracheal general anesthesia.
AB  - A series of 745 consecutive cases of endotracheal anesthesia were collected at
      the National Taiwan University Hospital. Evaluation of the oral conditions was
      performed before, during and after the anesthesia. Injuries to oral structures
      were recorded. An 18% incidence of oral injuries was noted and the frequency for
      dental damage was 12.1%. Maxillary incisors, especially the left ones, were
      accident-prone. Risk factors identified in this study included large decay or
      restoration, advanced periodontitis, presence of dental prosthesis, shedding
      deciduous tooth, class II jaw relationship and anterior crowding. More than one
      third of the complications occurred during the maintenance or emergence stage of
      the anesthesia. Recommendations for prevention and management of this problem
      were given.

PMID- 1977067
TI  - Phospholipid fatty acid composition of various mouse tissues after feeding alpha
      linolenate (18:3n-3) or eicosatrienoate (20:3n-3).
AB  - The selective incorporation of dietary alpha-linolenate (18:3n-3) and its
      elongation product, eicosatrienoate (20:3n-3), into various phospholipids (PL) of
      mouse liver, spleen, kidney, and heart, was examined in a two-week feeding trial
      by assessing mol % changes in associated fatty acids. Mice were fed fat-free AIN
      76A diets modified with either 2 wt% safflower oil (control); 1% safflower and 1%
      linolenate; or 1% safflower and 1% eicosatrienoate. After linolenate or
      eicosatrienoate feeding, 20:4n-6 was reduced by 36-50% in liver
      phosphatidylcholine (PC) and in liver and spleen phosphatidylethanolamine (PE).
      Linolenate was minimally incorporated into PL, but was desaturated and elongated
      to 20:5n-3, 22:5n-3, and 22:6n-3, with notable differences in the quantity of
      these n-3 derivatives associated with different tissues and PL. Eicosatrienoate
      was uniquely incorporated into the cardiolipin (CL) pool of all organs. There was
      also considerable retroconversion of 20:3n-3 to 18:3n-3 (PC,PE). Dietary
      eicosatrienoate may therefore affect metabolism in diverse ways--20:3n-3, which
      is retroconverted to 18:3n-3, may provide substrate for 20:5n-3 and 22:6n-3
      syntheses, whereas intact 20:3n-3 may be incorporated into the CL pool. Acyl
      modifications of CL are known to affect the activity of key innermitochondrial
      enzymes, such as cytochrome c oxidase.

PMID- 1977069
TI  - GABAA-receptor expressed from rat brain alpha- and beta-subunit cDNAs displays
      potentiation by benzodiazepine receptor ligands.
AB  - In mammalian brain, the activation of GABAA-receptors is associated with the
      opening of chloride channels, whose function can be allosterically modulated by
      drugs, in particular by ligands of the benzodiazepine receptor. Agonistic ligands
      potentiate while inverse agonists reduce the efficiency of GABA. We have cloned
      cDNAs encoding alpha 1- and beta 1-subunits of the GABAA-receptor from rat brain.
      When the corresponding RNAs were co-expressed in Xenopus oocytes. GABA-induced
      currents were recorded which were inhibited by bicuculline and potentiated by
      pentobarbital. GABA activated the channel in a weakly cooperative manner.
      Furthermore, the GABA-response was modulated by benzodiazepine receptor ligands.
      However, not only various agonists but also the antagonist flumazenil and the
      inverse agonist DMCM potentiated the GABA-response. Thus, alpha 1- and beta 1
      subunits are sufficient to form GABAA-receptors which contain benzodiazepine
      binding sites, although in a functionally restricted form.

PMID- 1977070
TI  - Influence of nigrostriatal dopaminergic tone on the biosynthesis of dynorphin and
      enkephalin in rat striatum.
AB  - The purpose of this study was to obtain direct evidence that the nigrostriatal
      dopamine (DA) pathway modulates the metabolism of striatal dynorphin and [Met5]
      enkephalin. This was achieved by repeated injections of apomorphine (APO) or D
      amphetamine (AMP) in unilateral nigral 6-hydroxydopamine (6-OHDA)-lesioned rats.
      Three weeks after a 6-OHDA lesion, dynorphin A(1-8)-like immunoreactivity (DN-LI)
      and the level of mRNA encoding prodynorphin in the striatum on the lesioned side
      were decreased compared with the contralateral control side. Activation of DA
      receptors by 7 daily injections of APO (5 mg/kg, Bid, s.c.), however, caused a
      large increase (3- to 4-fold of saline control) in striatal levels of DN-LI and
      prodynorphin mRNA on the 6-OHDA lesioned side, which is far greater than the
      increase on the contralateral side (2-fold of saline control). Presumably, the
      potentiated effect of APO in 6-OHDA lesioned rats is due to hypersensitivity of
      DA receptors resulting from DA denervation. Seven daily injections of AMP (5
      mg/kg, Bid, s.c.), a DA-releasing agent, increased striatal DN-LI (187% of saline
      control) on the non-lesioned side, but not on the 6-OHDA-lesioned side. Taken
      together, the data indicate that the nigrostriatal pathway exerts a tonic
      excitatory influence over the biosynthesis of dynorphin and that this influence
      is not maximal since an additional increase in dopaminergic tone further
      increases the expression of dynorphin. In contrast, [Met5]-enkephalin-like
      immunoreactivity (ME-LI) in the striatum was increased by a 6-OHDA-lesion (145%
      of contralateral control), which was blocked by repeated administration of APO
      but not AMP.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1977071
TI  - Relapsing encephalomyelitis following transfer of partial immunity to JHM virus.
AB  - Mice infected with the JHM strain mouse hepatitis virus (JHMV) develop a fatal
      encephalomyelitis with evidence of demyelination. It has previously been shown
      that the adoptive transfer of 5 x 10(7) nylon wool adherent (NWA) spleen cells
      from immunized donors to lethally infected recipients clears virus from the
      central nervous system (CNS) and prevents demyelination. Adoptive transfer of a
      smaller number (1 x 10(7] of NWA spleen cells from immunized donors also protects
      from death but does not significantly alter virus replication in the CNS during
      the acute phase of the infection. Moreover, these mice develop a transient non
      fatal encephalomyelitis which occurs approximately 3 weeks post-infection. This
      delayed encephalomyelitis is associated with a mononuclear cell infiltration into
      the CNS but little or no evidence of virus replication or increased viral
      antigen. A virus-specific delayed-type hypersensitivity (DTH) response precedes
      this delayed onset of disease by 24 to 48 h. Resolution of disease correlates
      with a selective and permanent suppression of the JHMV-specific DTH reactivity.
      In addition, no virus-specific DTH is detected following adoptive transfer of
      viral-specific DTH effectors derived from immunized donors. In contrast, these
      mice respond to a heterologous antigen, KLH, suggesting that the resolution of
      the encephalitis is accompanied by a profound suppression in viral-specific DTH
      response.

PMID- 1977073
TI  - Structure and function of haemolysin B,P-glycoprotein and other members of a
      novel family of membrane translocators.
AB  - Recent studies have identified two sub-families of highly conserved polypeptides
      in a wide variety of organisms concerned with the transport of many different
      compounds, specific for each transport protein. Both families, represented by
      HisP and HlyB, respectively, have in common a highly conserved, approximately 25
      kD domain, containing an ATP-binding site. The HisP sub-family essentially
      consists of cytoplasmic proteins which couple energy to the import of small
      substrates through cytoplasmic membrane permeases in Gram-negative bacteria. The
      HlyB (P-glycoprotein) sub-family, on the other hand, contains a second large
      domain which apparently acts as the transmembrane translocator itself, which in
      most cases drives the secretion of a variety of compounds. These membrane domains
      share a number of structural features which also serve to distinguish these
      proteins as a closely related group. Nevertheless, the compounds secreted by the
      HlyB sub-family include large polypeptides, polysaccharides and a variety of anti
      tumour drugs. We describe here the properties of each of these remarkable
      proteins and we speculate on their possible mechanism of action.

PMID- 1977072
TI  - G to A substitution in the promoter region of the apolipoprotein AI gene is
      associated with elevated serum apolipoprotein AI and high density lipoprotein
      cholesterol concentrations.
AB  - We have determined the sequence of 250 bases 5' of the transcriptional start site
      of the apolipoprotein AI gene in a human individual with high serum
      concentrations of apo AI. One of the alleles contained a G to A substitution at
      position -75, between the CACAT sequence and the TAAATA box, creating a tandem
      repeat, CAGGGC-CA*GGGC. The substitution destroys an MspI cutting site, and the
      polymerase chain reaction and MspI digestion were used to identify the presence
      of the A or G base. The frequency of the A substitution in 96 healthy men from
      Bristol was 0.11 and this was increased to 0.25 in men with serum apo AI
      concentrations greater than 180 mg/dl. Men with the A allele had significantly
      higher serum concentrations of apo AI, high density lipoprotein (HDL) cholesterol
      and HDL2 than those with the G allele. In this sample, variation associated with
      the G to A substitution accounted for 6% and 4.6% of the total variance in apo AI
      and HDL cholesterol concentrations, respectively. Although there is as yet no
      functional proof, it is possible that the A substitution may be having a direct
      positive effect on the rate of apo AI gene transcription and thus be associated
      with increased apo AI and HDL cholesterol concentrations because of increased
      production of apo AI protein from the liver or intestine.

PMID- 1977075
TI  - Metipranolol: a new beta-blocker for glaucoma.

PMID- 1977074
TI  - Neural pathways in chronic pain.
AB  - The evidence for changes in function of the central nervous system in cases of
      chronic pain is persuasive. We are not dealing with a passively wired system but
      one which changes structure and function and even connectivity in response to
      incoming sensory information. Whether these changes are capable of reversal with
      time and treatment remains to be shown. An optimist would suggest that
      physiological changes without abnormalities are indeed capable of reversal given
      time and appropriate neural input that matches normal non-painful afferent
      stimulation. That this is feasible is suggested by strategies of management with
      successful outcomes in patients with chronic pain, especially when pain is due to
      intermittent or limited ongoing stimulation of nociceptors. Clinical experience
      suggests, however, that deafferentation pain syndromes where pain is a
      consequence of damage directly to the nervous system cannot be viewed in such an
      optimistic light. A great deal more knowledge is required of how both the
      peripheral and central nervous system react to damage before we will be in a
      position to manage this source of chronic pain successfully.

PMID- 1977076
TI  - Abstracts from the Third International Conference on Molecular Biology and
      Pathology of Matrix. June 13-16, 1990.

PMID- 1977077
TI  - Symposium on interleukin-2 and activated killer cells. 2nd biennial conference on
      Chemotherapy of Infectious Diseases and Malignancies. Montreux, Switzerland,
      March 1989. Proceedings.

PMID- 1977078
TI  - The nature of ultraviolet light-induced mutations at the heterozygous aprt locus
      in Chinese hamster ovary cells.
AB  - A system for studying mutational specificity at a heterozygous locus in Chinese
      hamster ovary (CHO) cells is described. The strategy employed is based on
      restriction fragment analysis and DNA sequencing of enzymatically amplified
      mutant adenine phosphoribosyltransferase (aprt) alleles. We have demonstrated the
      usefulness of this approach through the characterization of a collection of aprt-
      mutants with respect to the role played by loss of heterozygosity events in
      ultraviolet light (UV) induced mutagenesis. A similar strategy has also been
      applied to speculate on the identity of the premutational lesion responsible for
      a UV-induced mutational hotspot at the aprt locus.

PMID- 1977079
TI  - A randomized controlled trial of a reduced daily dose of zidovudine in patients
      with the acquired immunodeficiency syndrome. The AIDS Clinical Trials Group.
AB  - BACKGROUND: The initially tested dose of zidovudine for the treatment of patients
      with advanced disease caused by the human immunodeficiency virus type 1 (HIV) was
      1500 mg. Although this dose is effective, it is associated with substantial
      toxicity. METHODS: To evaluate the efficacy and safety of a reduced dose, we
      conducted a randomized controlled trial in 524 subjects who had had a first
      episode of Pneumocystis carinii pneumonia. The subjects were assigned to receive
      zidovudine in either a dose of 250 mg taken orally every four hours (the standard
      treatment group, n = 262) or a dose of 200 mg taken orally every four hours for
      four weeks and thereafter 100 mg taken every four hours (the low-dose group, n =
      262). RESULTS: The median length of follow-up was 25.6 months. At 18 months the
      estimated survival rates were 52 percent for the standard-treatment group and 63
      percent for the low-dose group (P = 0.012 by the log-rank test). At 24 months the
      estimated survival rates were 27 percent for the standard-treatment group and 34
      percent for the low-dose group (P = 0.033). In both groups, 82 percent of the
      subjects had another opportunistic infection, and the length of time to that
      infection was similar in the two groups (P = 0.56 by the log-rank test). CD4 T
      lymphocyte counts improved transiently in both groups, and serum levels of HIV
      antigen decreased in the subjects with antigenemia. The hemoglobin level declined
      to less than 5 mmol per liter (80 g per liter) in 101 subjects in the standard
      treatment group and in 77 in the low-dose group (39 vs. 29 percent, P = 0.0009 by
      the log-rank test). The neutrophil count declined to less than 0.750 x 10(9) per
      liter in 134 subjects in the standard-treatment group and in 96 in the low-dose
      group (51 vs. 37 percent, P = 0.0001). CONCLUSIONS: The reduced daily dose of
      zidovudine used in this study was at least as effective as the standard dose and
      was less toxic; however, with the use of a four-week induction period with a high
      dose followed by low-dose treatment, severe anemia and neutropenia were common
      complications of treatment with zidovudine.

PMID- 1977081
TI  - Linkage of dominant hereditary spherocytosis to the gene for the erythrocyte
      membrane-skeleton protein ankyrin.

PMID- 1977080
TI  - A pilot study of low-dose zidovudine in human immunodeficiency virus infection.
AB  - BACKGROUND: Zidovudine delays the progression of human immunodeficiency virus
      (HIV) infection but is associated with hematologic toxicity at high doses.
      Regimens are needed that preserve or enhance efficacy and reduce toxicity.
      Acyclovir has been reported to potentiate the effect of zidovudine on HIV in
      vitro. METHODS: We conducted a Phase II open-label, dose-escalating trial to
      evaluate the clinical and antiviral effects of zidovudine at low (300 mg daily,
      28 subjects), medium (600 mg, 24 subjects), and high (1500 mg, 15 subjects)
      doses, either with or without acyclovir (4.8 g) by random assignment. The
      subjects had the acquired immunodeficiency syndrome (AIDS)-related complex, but
      not AIDS. All of them had either HIV p24 antigenemia or plasma viremia and CD4
      lymphocyte counts of 200 to 500 per cubic millimeter when they began treatment.
      RESULTS: Performance scores and fatigue improved the most in the low- and medium
      dose zidovudine groups (both P less than or equal to 0.025). Those assigned to
      low-dose zidovudine gained the most weight and had the greatest improvement in
      the mean CD4-lymphocyte count (from 321 per cubic millimeter at base line to 412
      per cubic millimeter after 12 weeks, P = 0.01). The proportion of subjects in
      whom HIV antigenemia resolved, the decrease in the level of antigenemia, and the
      reduction in the plasma virus titers were similar at all three doses. Subjects
      assigned to receive the low or medium dose who subsequently crossed over to the
      1500-mg dose (n = 19) did not have an increase in CD4-cell counts or a decline in
      levels of HIV antigen, but they did have dose-related toxicity. The addition of
      acyclovir to zidovudine was well tolerated, but it did not enhance any of
      zidovudine's antiretroviral effects. CONCLUSIONS: In this pilot study a very low
      dose of zidovudine (300 mg) had clinical and virologic effects similar to those
      of higher daily doses (600 and 1500 mg). The minimal effective dose of zidovudine
      for the treatment of HIV infection has yet to be determined, and further studies
      of very low daily doses are warranted.

PMID- 1977082
TI  - You can teach an old dog new tricks. How AIDS trials are pioneering new
      strategies.

PMID- 1977083
TI  - Inhibition by dopamine of (Na(+)+K+)ATPase activity in neostriatal neurons
      through D1 and D2 dopamine receptor synergism.
AB  - The (Na(+)+K+)ATPase, an integral membrane protein located in virtually all
      animal cells, couples the hydrolysis of ATP to the countertransport of Na+ and K+
      ions across the plasma membrane. In neurons, a large portion of cellular energy
      is expended by this enzyme to maintain the ionic gradients that underlie resting
      and action potentials. Although neurotransmitter regulation of the enzyme in
      brain has been reported, such regulation has been characterized either as a
      nonspecific phenomenon or as an indirect effect of neurotransmitter-induced
      changes in ionic gradients. We report here that the neurotransmitter dopamine,
      through a synergistic effect on D1 and D2 receptors, inhibits the
      (Na(+)+K+)ATPase activity of isolated striatal neurons. Our data provide
      unequivocal evidence for regulation by a neurotransmitter of a neuronal ion pump.
      They also demonstrate that synergism between D1 and D2 receptors, which underlies
      many of the electrophysical and behavioural effects of dopamine in the mammalian
      brain, can occur on the same neuron. In addition, the results support the
      possibility that dopamine and other neurotransmitters can regulate neuronal
      excitability through the novel mechanism of pump inhibition.

PMID- 1977084
TI  - Two components of long-term potentiation induced by different patterns of
      afferent activation.
AB  - Long-term potentiation (LTP) of excitatory synaptic transmission could be a
      mechanism underlying memory. Induction of LTP requires Ca2+ influx into
      postsynaptic neurons through ion channels gated by NMDA (N-methyl-D-aspartate)
      receptors in hippocampus (area CA1 and dentate gyrus) and neocortex. Here we
      report that a component of LTP not requiring the activation of NMDA receptors can
      be induced in area CA1. The component is dependent on tetanus frequency, requires
      increases in postsynaptic intracellular Ca2+ concentrations, and is suppressed by
      an antagonist of voltage-dependent Ca2+ channels.

PMID- 1977085
TI  - Dwarf locus mutants lacking three pituitary cell types result from mutations in
      the POU-domain gene pit-1.
AB  - Mutations at the mouse dwarf locus (dw) interrupt the normal development of the
      anterior pituitary gland, resulting in the loss of expression of growth hormone,
      prolactin and thyroid-stimulating hormone, and hypoplasia of their respective
      cell types. Disruptions in the gene encoding the POU-domain transcription factor,
      Pit-1, occur in both characterized alleles of the dwarf locus. The data indicate
      that Pit-1 is necessary for the specification of the phenotype of three cell
      types in the anterior pituitary, and directly link a transcription factor to
      commitment and progression events in mammalian organogenesis.

PMID- 1977086
TI  - Formation of amyloid-like fibrils in COS cells overexpressing part of the
      Alzheimer amyloid protein precursor.
AB  - A pathological hallmark of Alzheimer's disease is the deposition of amyloid
      fibrils in the brain. The principal component of the amyloid fibril is beta/A4
      protein, which is derived from a large membrane-bound glycoprotein, Alzheimer
      amyloid protein precursor (APP). Although the deposition of amyloid is thought to
      result from the aberrant processing of APP, the detailed molecular mechanisms of
      amyloidogenesis remain unclear. A C-terminal fragment of APP which spans the
      beta/A4 and cytoplasmic domains has a tendency to self-aggregate. In an attempt
      to establish a cultured-cell model for amyloid fibril formation, we have
      transfected COS-1 cells with complementary DNA encoding the C-terminal 100
      residues of APP. In the perinuclear regions of a small population of DNA
      transfected cells, we observed inclusion-like deposits which showed a strong
      immunohistochemical reaction towards an anti-C-terminal APP antibody or an anti
      beta/A4 amyloid core-specific antibody. Electron microscope observations of the
      inclusion-carrying cells revealed an accumulation of amyloid-like fibrils of 8-22
      nm diameter near and on the nuclear membrane. The fibrils showed a beaded or
      helical structure, and reacted positively with the anti-C-terminus antibody by
      immunoelectron microscopy. These results suggest that the formation of amyloid
      fibrils is an inherent characteristic of the C-terminal peptide of APP. The
      present system provides a suitable model for the molecular dissection of the
      process of brain amyloidogenesis.

PMID- 1977087
TI  - Retinal degeneration in the rd mouse is caused by a defect in the beta subunit of
      rod cGMP-phosphodiesterase.
AB  - Mice homozygous for the rd mutation display hereditary retinal degeneration and
      the classic rd lines serve as a model for human retinitis pigmentosa. In affected
      animals the retinal rod photoreceptor cells begin degenerating at about postnatal
      day 8, and by four weeks no photoreceptors are left. Degeneration is preceded by
      accumulation of cyclic GMP in the retina and is correlated with deficient
      activity of the rod photoreceptor cGMP-phosphodiesterase. We have recently
      isolated a candidate complementary DNA for the rd gene from a mouse retinal
      library and completed the characterization of cDNAs encoding all subunits of
      bovine photoreceptor phosphodiesterase. The candidate cDNA shows strong homology
      with a cDNA encoding the bovine phosphodiesterase beta subunit. Here we present
      evidence that the candidate cDNA is the murine homologue of bovine
      phosphodiesterase beta cDNA. We conclude that the mouse rd locus encodes the rod
      photoreceptor cGMP-phosphodiesterase beta subunit.

PMID- 1977088
TI  - Binding of yeast a1 and alpha 2 as a heterodimer to the operator DNA of a haploid
      specific gene.
AB  - The mating-type locus (MAT) encodes several DNA-binding proteins, which determine
      the three cell types of Saccharomyces cerevisiae: the a and alpha haploid cell
      types, and the a/alpha diploid cell type. One of the products of MAT, alpha 2,
      functions in two cell types. In alpha cells, alpha 2 represses the a-specific
      genes by binding to the operator as a dimer. In a/alpha diploid cells, alpha 2
      acts with a1, a product of the other MAT allele, to repress a different set of
      genes, the haploid-specific genes. Until now, the nature of the interaction
      between a1 and alpha 2 was not known, although it had been suggested that alpha 2
      may form a heterodimer with a1. I show, by using proteins synthesized in vitro,
      that a1 and alpha 2 bind the operator of a haploid-specific gene as a
      heterodimer. The ability of alpha 2 to form both homodimers and heterodimers with
      a1, each with a different DNA-binding specificity, explains the dual regulatory
      functions of alpha 2. This is the first example of regulation by
      heterodimerization among homeobox-containing proteins, a class that includes
      proteins responsible for the specification of segment identity in Drosophila,
      mammals and other eukaryotes.

PMID- 1977089
TI  - Nizatidine versus ranitidine in the treatment of peptic ulcer disease: report on
      the Dutch investigation as part of a European multicentre trial.
AB  - The efficacy and safety of nizatidine was evaluated in comparison with ranitidine
      in 230 patients with endoscopically documented gastric (71) or duodenal (159)
      ulcers. Gastric ulcer patients who satisfied all criteria for inclusion and
      exclusion were randomly allocated to nizatidine 300 mg nocte, 150 mg b.d. or
      ranitidine 150 mg b.d., duodenal ulcer patients to nizatidine 300 mg nocte or
      ranitidine 300 mg nocte. Endoscopic healing was defined as complete
      epithelialisation of all mucosal lesions. Endoscopy was performed at 4 and, if
      not healed, at 8 weeks. Healing rates were shown to be comparable for all
      treatment regimens. In both duodenal ulcer treatment groups, and with both drugs,
      healing was negatively influenced by ulcer size, ulcer number, smoking habits and
      a disease duration of 5 years or more. Few side effects were noted. Nizatidine,
      administered as a 300 mg nocte and as a 150 mg b.d. dose appeared to be a safe H2
      antagonist and was as effective as ranitidine in the treatment of duodenal and
      gastric ulceration.

PMID- 1977090
TI  - Induction of glutamine synthetase by 8-bromo cyclic AMP in primary cultures of
      rat brain astrocytes.
AB  - Glutamine synthetase (GS) is the key enzyme in cerebral glutamine production.
      Understanding the regulation of the expression of GS is important for definition
      of the control of glutamine metabolism in brain. Therefore, we studied the
      control of GS expression by 8-bromo cyclic AMP in primary cultures of astrocytes
      prepared from brains of neonatal rats. GS activity was increased by 8-bromo
      cyclic AMP in a dose- and time-dependent manner. This increase was associated
      with a corresponding increase in the steady-state level of GS mRNA.

PMID- 1977092
TI  - Transmitter release in hippocampal slices from rats with limbic seizures produced
      by systemic administration of kainic acid.
AB  - The systemic injection of kainic acid (KA) has been shown to destroy neurons in
      the hippocampus and to induce limbic-type seizure activity. However, little is
      known on the neurochemical events that are associated with this convulsant
      effect. In the present work we studied the spontaneous and the K(+)-stimulated
      release of labeled tau-aminobutyric acid (GABA), glutamate, serotonin and
      dopamine, in hippocampal slices of KA-treated rats, at the moment of clinical
      seizures (2 h) and 72 h later. At the onset of convulsions we found a 40-45%
      decrease in the K(+)-stimulated release of GABA. The release of the other
      neurotransmitters was not significantly affected by KA treatment. After 72 h GABA
      release was still reduced by 30-40%. It is concluded that the epileptogenic
      effect of KA in the hippocampus is probably related to a diminished inhibitory
      GABAergic neurotransmission.

PMID- 1977091
TI  - Spinal cord ischemia-induced elevation of amino acids: extracellular measurement
      with microdialysis.
AB  - Excitatory amino acids have been implicated in the production of calcium mediated
      neuronal death following central nervous system ischemia. We have used
      microdialysis to investigate changes in the extracellular concentrations of amino
      acids in the spinal cord after aortic occlusion in the rabbit. Glutamate,
      aspartate, glutamine, asparagine, glycine, taurine, valine, and leucine were
      measured in the microdialysis perfusate by high pressure liquid chromatography.
      The concentrations of glutamate, glycine, and taurine were significantly higher
      during ischemia and reperfusion than controls. Delayed elevations in the
      concentrations of asparagine and valine were also detected. The elevation of
      glutamate is consistent with the hypothesis that excitotoxins may mediate
      neuronal damage in the ischemic spinal cord. Increased extracellular
      concentrations of asparagine and valine may reflect preferential use of amino
      acids for energy metabolism under ischemic conditions. The significance of
      increased concentrations of inhibitory amino acid neurotransmitters is unclear.

PMID- 1977094
TI  - 30th international Neuropsychiatric Symposium. Pula, 10th-16th June 1990.
      Abstracts.

PMID- 1977093
TI  - Solubilization and reconstitution of dopamine D1 receptor from bovine striatal
      membranes: effects of agonist and antagonist pretreatment.
AB  - The bovine striatal dopamine D1 receptor was solubilized with a combination of
      sodium cholate and NaCl in the presence of phospholipids, following treatment of
      membranes with a dopaminergic agonist (SKF-82526-J) or antagonist (SCH-23390).
      The solubilized receptors were subsequently reconstituted into lipid vesicles by
      gel-filtration. A comparison of ligand-binding properties shows that the
      solubilized and reconstituted receptors bound [3H]SCH-23390 to a homogeneous site
      in a saturable, stereospecific and reversible manner with a Kd of 0.95 and 1.1 nM
      and a Bmax of 918 and 885 fmol/mg protein respectively for agonist- and
      antagonist-pretreated preparations. These values are very similar to those
      obtained for membrane-bound receptors. The competition of antagonists for [3H]SCH
      23390 binding exhibited a clear D1 dopaminergic order in the reconstituted
      preparation obtained from either agonist or antagonist-pretreated membranes,
      except that (+)butaclamol was about four-fold more potent than cis-flupentixol in
      displacing [3H]SCH-23390 binding in preparation obtained from agonist-pretreated
      membranes compared to antagonist-pretreated membranes. The agonist/[3H]SCH-23390
      competition studies revealed the presence of a high-affinity component of agonist
      binding in both the reconstituted receptor preparations. The number of high
      affinity agonist binding sites, however, is 40-80% higher in reconstituted
      preparation obtained from antagonist-treated membrane compared to that obtained
      from the agonist-treated membrane. In both the preparations, 100 microM
      guanylylimidodiphosphate (Gpp(NH)p) completely abolished the high-affinity
      component of agonist binding compared to partial abolition in the native
      membranes, indicating a close association of a G-protein with the solubilized
      receptors. Whether the receptor was solubilized following agonist or antagonist
      preincubation of the membranes, the receptor-detergent complex eluted from a
      steric-exclusion HPLC column with an apparent molecular size of 360,000.
      Preincubation of the solubilized preparations with Gpp(NH)p had virtually no
      effect on the elution profile suggesting a lack of guanine nucleotide-dependent
      dissociation of G-protein receptor complex.

PMID- 1977096
TI  - Influence of neurohypophyseal peptides on the formation of active avoidance
      conditioned reflex behavior.
AB  - The role of lysine-vasopressin and oxytocin, as well as of their analog and
      fragment (DGAVP, desglycinamide arginine vasopressin; PLG, prolyl-leucyl-glycyl
      amine), microinjected into the ventral hippocampus, in the formation and
      extinction of active avoidance conditioned reflex, was investigated. It was
      established that the introduction of lysine-vasopressin, as well as of its
      analog, into the hippocampus promoted the improvement of the formation of the
      avoidance reaction, while an inhibitory effect was elicited in the period of
      extinction of the skill. The opposite effects on the active avoidance reaction
      were obtained with oxytocin and its fragments. It is hypothesized that the
      observed behavioral changes in the active avoidance reaction are associated with
      the influence of these peptides on the processes of learning and memory.

PMID- 1977095
TI  - Role of arachidonic acid or its metabolites in growth-hormone-releasing factor
      induced release of somatostatin from the median eminence.
AB  - The possible involvement of arachidonic acid (AA) release in growth-hormone
      releasing factor (GRF)-induced somatostatin (SRIF) release from the median
      eminence (ME) of the hypothalamus was evaluated in adult male rats using an in
      vitro incubation system. The MEs were preincubated with [14C]-AA, then washed and
      incubated with vehicle or test agents, and the release of SRIF and [14C]-AA into
      the medium was measured. In the experiments designed only to determine SRIF
      release, the MEs were first preincubated for 30 min. The medium was then
      discarded and replaced with fresh buffer or test substances and incubated for 10,
      20 and/or 30 min. GRF (10(-10) M) stimulated both AA and SRIF release
      significantly within 20 min, with maximum release occurring at 30 min. The
      stimulatory effect of GRF on AA release was coincident with the release of SRIF.
      A phospholipase A2 inhibitor (10(-6) M, quinacrine) completely abolished the
      stimulatory effect of GRF on both AA and SRIF release. The release of SRIF
      induced by GRF was also inhibited by both indomethacin (10(-6) M, a
      cyclooxygenase inhibitor) and metyrapone (10(-6) M, a cytochrome P-450
      inhibitor). On the other hand, nordihydroguaiaretic acid (10(-6) M, a
      lipoxygenase inhibitor) had no effect on GRF-evoked SRIF release. The data
      presented here suggest that an important GRF-mediated event leading to SRIF
      secretion is an elevated release of AA from ME fragments in vitro. In conclusion,
      our data are suggestive that the stimulatory effect of GRF on SRIF release is
      due, in part, to the release and subsequent metabolism of AA to one or more
      metabolites.

PMID- 1977097
TI  - D-aspartate release from cerebellar astrocytes: modulation of the high K-induced
      release by neurotransmitter amino acids.
AB  - The properties of D-aspartate release were studied in cerebellar astrocytes (14
      15 DIV) in primary cultures in the rat. The spontaneous release of D-aspartate
      from astrocytes was fast, being further enhanced in Na- and Ca-free (EDTA
      containing) media. Kainate, quisqualate, D-aspartate and L-glutamate stimulated
      the release, whereas L-glutamatediethylester was inhibitory. The release was
      enhanced by veratridine and high K (50 mM). Substitution of chloride by acetate
      in the experimental medium did not change the basal release but slightly
      decreased the potassium-induced release, indicating that the high K-induced D
      aspartate release is primarily due to depolarization of cells. The K-stimulated
      release was independent of extracellular Ca2+ and potentiated by kainate and
      quisqualate. The effect of kainate was reduced by kynurenate, and that of
      quisqualate by L-glutamatediethylester. Glycine, taurine and GABA were equally
      effective in depressing the stimulated release of D-aspartate. The inhibition of
      GABA could be blocked by GABA antagonists. The results suggest that inhibitory
      amino acids may be involved in the regulation of glutamate release from
      cerebellar astrocytes. A further implication is that cerebellar astrocytes
      possess functional glutamate receptors of kainate and quisqualate subtypes.

PMID- 1977098
TI  - Gliotoxic effects of alpha-aminoadipic acid isomers on the carp retina: a long
      term observation.
AB  - The glutamate analogue, alpha-aminoadipic acid was intravitreally administered in
      the D-, DL- and L-forms to carp (Cyprinus carpio) retina in vivo. To make a
      quantitative assessment of its gliotoxic action, the activity of glutamine
      synthetase, whose localization was confirmed in glial Muller cells by an
      immunohistochemical technique, was examined at various intervals over one month.
      Intravitreal injection of 8 mumol alpha-aminoadipic acids reduced the glutamine
      synthetase activity within 4 h and maximally by 24 h. The maximum reduction
      evoked by L-, DL- and D-forms was about 65, 45 and 28% in reduction, and their
      minimum effective dose was 0.8, 1.5 and 2.0 mumol, respectively. At three to four
      days after alpha-aminoadipic acids injection, sodium dodecyl sulphate gel
      electrophoresis suggested that some retinal proteins including glutamine
      synthetase were significantly reduced, whilst others were increased. These
      biochemical changes were fully reversed one to two weeks after administration of
      the D- or DL-forms, but not until one month with the L-form. The
      electroretinographic b-wave, reflecting glial activity, was completely blocked by
      8 mumol alpha-aminoadipic acids within 4 h. The electroretinographic b-wave was
      recovered first in the case of D- and then of DL-form at two to three weeks after
      injection, but only 50% recovery was seen in the case of L-form even two months
      later. A high dose of DL-alpha-aminoadipic acid (16 mumol) induced as long
      lasting a suppression in the glutamine synthetase and electroretinographic b-wave
      activities as 8 mumol L-alpha-aminoadipic acid. Therefore, the gliotoxic efficacy
      of L-alpha-aminoadipic acid at micromol orders was two-fold higher than that of
      DL-alpha-aminoadipic acid. Differences in the time-course of recovery of the
      suppression of glutamate synthetase and electroretinographic b-wave activities
      induced by alpha-aminoadipic acids are discussed in terms of its gliotoxicity.

PMID- 1977099
TI  - Atrial natriuretic factor is a new neuromodulatory peptide.
AB  - In this commentary, we will briefly discuss the potential regulatory role of
      atrial natriuretic factor in peripheral autonomic nervous system function. The
      focus will be on atrial natriuretic factor's involvement in cardiovascular
      homeostasis through its peripheral effect on sympathetic nervous activity, which
      may complement its humoral role. [Kuchel et al. (1987) Life Sci. 40, 1545-1551;
      Lang et al. (1985) Nature 314, 264-266]. We will attempt to support the
      hypothesis of its neuromodulatory action on efferent autonomic outflow.
      Specifically, the role of atrial natriuretic factor in the regulation of the
      synthesis and release of neurotransmitters and in synaptic transmission at the
      level of the sympathetic ganglia will be outlined. Its potential usefulness in
      neurobiological studies will also be indicated.

PMID- 1977101
TI  - The monoaminergic innervation of the amygdala in the squirrel monkey: an
      immunohistochemical study.
AB  - The monoaminergic innervation of the amygdala of the squirrel monkey (Saimiri
      sciureus) was studied by using immunohistochemical methods with primary antisera
      raised against serotonin, and the catecholamine synthesizing enzymes tyrosine
      hydroxylase, dopamine-beta-hydroxylase and phenylethanolamine-N
      methyltransferase. Serotonin was widely distributed within the amygdala including
      profuse terminal labeling in central, basolateral and cortical nuclear groups.
      The accessory basal and medial nuclei were the only two areas receiving
      relatively poor serotoninergic innervation. Tyrosine hydroxylase was more
      discretely distributed, with very dense to moderate terminal labeling in central,
      basal and lateral nuclei, but only scant labeling within accessory basal and
      corticomedial nuclei, except at the cortical transitional area where dense
      terminal labeling was noted. Dopamine-beta-hydroxylase immunoreactivity was
      moderate in central and corticomedial nuclei, but comparatively light in other
      nuclear groups. Phenylethanolamine-N-methyltransferase was only sparsely
      distributed in the amygdala. The findings of the present study reveal that the
      monoaminergic innervation of the primate amygdala is similar to that reported in
      rodents, although some conspicuous exceptions do exist. Whereas the noradrenergic
      and serotoninergic neuronal systems ramify profusely within the amygdala, the
      dopaminergic system appears to be more discretely and topographically organized.

PMID- 1977100
TI  - Laminar distributions of muscarinic acetylcholine, serotonin, GABA and opioid
      receptors in human posterior cingulate cortex.
AB  - Experimental animal studies have demonstrated a number of receptor localizations
      on specific cortical afferents and neurons. The present study of human posterior
      cingulate cortex evaluates the laminar distributions of particular receptors and
      their likely association with components of the neuropil. Coverslip
      autoradiographic and single grain counting techniques were used followed by
      heterogeneity analysis in which the layer of peak binding and an index of
      heterogeneity were determined for each ligand. The index was calculated by
      determining specific binding by layer as a percentage of binding in all layers.
      The differences from an absolutely homogeneous distribution, i.e. 11.1% for each
      of nine layers, were subtracted and the absolute laminar differences summed to
      form the index. High indices of over 15 reflected heterogeneous binding patterns
      in neocortex. The binding of ligands for muscarinic acetylcholine, serotonin,
      opioid, GABA and beta adrenoceptors was evaluated. Pirenzepine binding peaked in
      layer II of area 23a but was extremely homogeneous with an index of heterogeneity
      of 8.9. In contrast, oxotremorine-M binding had a peak in layer IIIc and an index
      of 16.4, while AF-DX 116 binding peaked in layer IIIa-b and had an index of 30.6.
      Of the ligands for serotonin uptake and receptor binding paroxetine binding was
      evenly distributed in layers I-III and had a low index of heterogeneity of 9.8.
      Ketanserin binding was also homogeneous and, since it had an index of 8.9, this
      pattern was virtually the same as that for paroxetine. In contrast, serotonin and
      8-hydroxy-2-(di-n-propylamino)tetralin binding peaked in layer II and had very
      high indices of 20.8 and 50.3, respectively, suggesting only a limited
      association with that of the paroxetine distribution. Finally, there were three
      layers which contained peaks in binding for ligands for opioid, GABA and beta
      adrenoceptors. Firstly, layer Ia had peak dynorphin-A binding, the latter of
      which had an index of 22.6. Secondly, Tyr-D-Ala-Gly-MePhe-Gly-ol and 2-D
      penicillamine-5-D-penicillamine-enkephalin binding peaked in layer II and had
      indices of 8.6 and 17.4, respectively. Thirdly, muscimol and (-)-cyanopindolol
      binding peaked in layer IIIa-b and had indices of 29.6 and 11.1, respectively.
      When viewed in the context of experimental animal studies, it is likely that
      heterogeneities in oxotremorine-M and paroxetine binding are associated with the
      termination of the thalamic and raphe nuclei, respectively. While serotonin 2
      receptors are co-distributed with serotonin uptake sites, serotonin 1A receptors
      have a significant mismatch with these sites.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1977102
TI  - Neuroexcitatory plasma amino acids are elevated in migraine.
AB  - To investigate the role of glutamic (Glu) and aspartic acid (Asp) in migraine, we
      measured the plasma amino acids in migraine patients with and without aura,
      between and during attacks, and compared the profiles with the plasma amino acid
      profiles of tension headache patients and healthy controls. Between attacks,
      migraineurs (notably with aura) had substantially higher plasma Glu and Asp
      levels than did controls and tension headache patients. In addition, patients
      with migraine without aura showed low plasma histidine levels. During migraine
      attacks, Glu (and to a lesser extent Asp) levels were even further increased. The
      results suggest a defective cellular reuptake mechanism for Glu and Asp in
      migraineurs, and we hypothesize a similar defect at the neuronal/glial cell
      level, predisposing the brain of migraineurs to develop spreading depression.

PMID- 1977103
TI  - Emerging strategies in Parkinson's disease. Report of a symposium. Chicago, March
      24, 1990. Proceedings.

PMID- 1977104
TI  - Dopaminergic agonists in the treatment of Parkinson's disease.

PMID- 1977105
TI  - [Autocontrol of muscle relaxation with vecuronium].
AB  - The optimal conditions for maintaining desired levels of muscle relaxation with
      vecuronium are obtained by means of the continuous infusion (I.V.) technique. A
      frequent correction of the infusion flow is required, since it is impossible to
      predict the exact amount for the muscle relaxant in single case. In order to
      overcome such limits the authors propose a very feasible infusion system for the
      self-control of muscle relaxation; furthermore they positively consider its
      possible daily clinical application.

PMID- 1977106
TI  - [Systemic lupus erythematosus induced by drugs].
AB  - The clinical and morphological characteristics of drug-induced lupus (DIL) are
      not unlike those of systemic lupus erythematosus (SLE). However, DIL is
      characterised by several distinct features: the two sexes are equally affected;
      onset occurs in advanced middle-age; the black population is seldom affected.
      Genetic predisposition seems to influence the onset of disease: subjects affected
      by DIL are prevalently HLA-DR4 haplotypes with a slow acetylator condition.
      Modifications in humoral immunity include the presence of anti-nuclear
      antibodies, denatured anti-DNA antibodies, and antihistone antibodies. Likewise,
      anti-lymphocytotoxic antibodies, increased ESR and hypocomplementemia are often
      observed. Little is known about alterations in cellular immunity but the
      dysregulation of lymphocyte T-helper and T-suppressor activity may be an
      important feature. Drugs most often leading to DIL include hydralazine, beta
      blockers, procainamide and hydantoin. Current pathogenetic theories include a
      possible immune drug-DNA cross-reaction, the induction of new antigenic
      structures, an interaction between drugs and immunomodulating cells.

PMID- 1977107
TI  - Distribution of neuropeptide Y-like immunoreactive perikarya and processes in the
      medulla of the cat.
AB  - Neuropeptide Y-like immunoreactive (NPY-LI) perikarya and processes have been
      identified in the medulla of the cat. NPY-LI perikarya were found in 4 regions;
      (1) the medial N. of the solitary tract (MNTS), (2) the lateral tegmental field
      (LTF), (3) the ventrolateral medullary surface (VLMS), and (4) in the spinal
      trigeminal nucleus. Tyrosine hydroxylase-like immunoreactive (TH-LI) neurons were
      also found in the first 3 regions noted above. NPY-LI and TH-LI neurons had a
      similar morphology and distribution. NPY-LI and TH-LI neurons were counted in
      sections from 3 representative levels of the medulla. NPY-LI cells were most
      numerous in the LTF, especially at the level of the area postrema and more
      rostrally. The lowest number of NPY-LI cells was seen in the MNTS, particularly
      at a level caudal to the area postrema. NPY-LI cells were at least 3-fold less
      numerous than TH-LI cells at all levels of the MNTS, but there was a 27-fold
      greater number of TH-LI neurons at a level of MNTS caudal to the area postrema.
      In the LTF, NPY-LI cells were 2- to 5-fold less common than TH-LI cells.
      Approximately equal numbers of NPY-LI and TH-LI cells were counted in the VLMS at
      the level of the area postrema and rostrally. These data indicate that the
      majority of TH-LI cells in the MNTS of the cat probably do not contain NPY as a
      co-transmitter.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1977108
TI  - Calbindin immunoreactivity in sensory and autonomic ganglia in the guinea pig.
AB  - Immunoreactivity (IR) for the calcium binding protein, calbindin, was localized
      in sensory ganglia (nodose, trigeminal and dorsal root), in parasympathetic
      ganglia (otic and sphenopalatine) in sympathetic chain ganglia and in sympathetic
      pre-vertebral ganglia of guinea pig. In sensory ganglia, fine nerve fibres with
      calbindin-IR surrounded the majority of cell bodies, a low proportion of which
      were themselves reactive. In cranial parasympathetic and in sympathetic chain
      ganglia, a small proportion of nerve cells was surrounded with baskets of
      calbindin-IR nerve fibres, but very few cell bodies were reactive. In
      prevertebral sympathetic ganglia, dense networks of terminals surrounded many
      cell bodies, but few somata were themselves reactive. In the coeliac and inferior
      mesenteric ganglia, the calbindin-IR nerve fibres surrounded somatostatin-IR cell
      bodies, but not those with neuropeptide Y-IR. It is concluded that specific
      subgroups of peripheral autonomic and sensory neurones have calbindin-IR.

PMID- 1977109
TI  - Quantal secretion and loss of vesicles induced by veratridine at the crayfish
      neuromuscular junction.
AB  - Experiments were conducted in nerve-muscle preparations of small young crayfish
      (Austropotamobius torrentium, Astacus astacus). Application of veratridine in the
      superfusate induced strong quantal release of transmitter. After about 5 min when
      quantal release had declined to a low level preparations were fixed for electron
      microscopy. Unlike control preparations, veratridine-treated preparations
      revealed nerve terminals which were largely depleted of their synaptic vesicles.
      Our findings suggest that in the presence of veratridine the decline of quantal
      secretion results from the loss of vesicles caused by tonic nerve terminal
      depolarization. Moreover, our results indicate that during or after excessive
      quantal release triggered by veratridine synaptic vesicles may fuse with both the
      presynaptic membrane and each other.

PMID- 1977110
TI  - Effects of inactivation of D1 dopamine receptors on stereotypic and thermic
      responses to quinpirole (LY 171555).
AB  - The purpose of the present study was to investigate reports that the expression
      of dopamine agonist-induced behaviours is dependent upon the ratio of D1 to D2
      receptor activation. Selective inactivation of the D1 dopamine receptor was
      achieved using the irreversible antagonist N-ethoxycarbonyl-2-ethoxy-1,2
      dihydroquinoline (EEDQ) while D2 receptors were maintained at control levels by
      the use of a D2 antagonist, raclopride. Stereotypic and hypothermic responses to
      quinpirole (LY 171555) were assessed and related to striatal D1 and D2 receptor
      concentrations. Results showed that the incidence of stereotyped sniffing
      behaviour induced by LY 171555 was reduced in parallel with D1 receptor loss and
      sniffing behaviour was abolished at low D1 receptor (less than 40% of control)
      concentrations. Hypothermic responses to LY 171555 were unaffected by D1 receptor
      loss. These findings suggest that activation of D1 receptors is a critical
      component of stereotypic, but not hypothermic, responses to LY 171555, the
      magnitude of the sniffing response being positively associated with D1 receptor
      concentration.

PMID- 1977111
TI  - Somatostatin is increased in the dorsal root ganglia of adjuvant-inflamed rat.
AB  - To determine whether biosynthesis of somatostatin is enhanced in the primary
      sensory neurons by inflammatory pain, we examined the effects of adjuvant
      inoculation on the content of immunoreactive somatostatin, mainly composed of
      somatostatin-14 and somatostatin-28, in the dorsal root ganglia and the spinal
      cord of the rat. The adjuvant inoculation, which produced long-lasting
      inflammation and hyperalgesia, increased the content of immunoreactive
      somatostatin, especially somatostatin-14, in the dorsal root ganglia at L4-L6
      levels with no change in the dorsal and ventral horns of lumbar enlargement. Such
      an increase was enhanced by an intrathecal injection of colchicine (0.2 mg) that
      inhibits axonal flow of somatostatin. Chronic administration of the anti
      inflammatory analgesic, sodium diclofenac (3 mg.kg-1.d-1), abolished an adjuvant
      induced increase in the content of immunoreactive somatostatin in the dorsal root
      ganglia. These results suggest that the turnover (biosynthesis and axonal flow)
      of somatostatin in the primary sensory neurons is enhanced in the presence of
      persisting inflammatory pain, and support the idea that somatostatin-containing
      primary afferents are involved in the transmission of pain in the spinal dorsal
      horn.

PMID- 1977112
TI  - Inappropriate use of inhaled beta agonists in asthma.

PMID- 1977113
TI  - A preliminary experience with turbohaler.

PMID- 1977115
TI  - Risk management for extrapyramidal symptoms.

PMID- 1977114
TI  - Immunohistochemical study of oral lesions of lichen planus: diagnostic and
      pathophysiologic aspects.
AB  - The immunophenotype of lymphoid cells in the epithelium and lamina propria of the
      oral mucosa were examined in patients with lichen planus, nondysplastic
      leukoplakia, leukoplakia with lichen planus, and other unrelated lesions. In all
      groups T lymphocytes were predominant; however, the T4/T8 lymphocyte ratio was
      higher with lichen planus than with other groups. This may be of diagnostic value
      in the histologic evaluation of oral lesions not typical of lichen planus.
      Finally, a higher percentage of Langerhans cells were observed in lichen planus.
      An immunologic pathogenesis of lichen planus is proposed.

PMID- 1977116
TI  - [7 cases of polyarteritis nodosa].
AB  - The recognition of polyarteriitis nodosa is a difficult task for the clinician.
      The extraordinarily varied symptoms of this illness involve mostly general
      complaints and the mostley combination of some organic symptoms. In their
      histologically proved seven cases the most frequent original clinical symptoms
      were the long lasting feverish condition, the loss of body weight as well as
      numbness and pain of limbs. The anamnesis of three patients involved the asthma
      bronchiale. The laboratory findings were characterized first of all by an
      accelerated erythrocyte sedimentation rate and in four cases anaemia has
      developed. In four cases eosinophilia and in two ones high blood-pressure were
      observed. The disease-process of their patients is varying; a 30 year old man's
      death was caused right after the admission to the hospital by an acute myocardial
      infarction.

PMID- 1977117
TI  - Variation in the protein coding region of the human p53 gene.
AB  - This report describes a restriction fragment length polymorphism for the enzyme
      BglII caused by a conserved C to T change at residue 21 of the human p53 gene.
      This RFLP could potentially be misinterpreted as a rearrangement or a point
      mutation if paired constitutional tissue is not simultaneously analyzed.

PMID- 1977118
TI  - A HaeIII polymorphism at the D10S101 locus.

PMID- 1977119
TI  - PvuII polymorphism at the COL1A2 locus.

PMID- 1977120
TI  - BanI polymorphism at the XBP1 locus.

PMID- 1977121
TI  - PCR detection of the BgIII RFLP at the RBP3 locus.

PMID- 1977122
TI  - PstI RFLP of the CGB gene.

PMID- 1977123
TI  - StyI polymorphism at the D15S11 locus.

PMID- 1977124
TI  - A PstI polymorphism at the D5S39 locus.

PMID- 1977125
TI  - A BamHI polymorphism at the DBH locus.

PMID- 1977126
TI  - TaqI polymorphism at the human complement component C9 gene.

PMID- 1977127
TI  - CRI-J177 (DYS152): a polymorphic Y chromosome locus.

PMID- 1977128
TI  - Two polymorphisms at the locus D698 defined by a YAC.

PMID- 1977129
TI  - BclI RFLP in fucosidase pseudogene (FUCA1P).

PMID- 1977130
TI  - DdeI polymorphism in intron 5 of the ATIII gene.

PMID- 1977131
TI  - HgiAI polymorphism near the HMGCR promoter.

PMID- 1977132
TI  - ScrFI polymorphism in the 2nd intron of the HMGCR gene.

PMID- 1977133
TI  - PCR detection of the TAQ1 polymorphism at the CA2 locus.

PMID- 1977134
TI  - The promoter of the human parathyroid hormone gene contains a functional cyclic
      AMP-response element.
AB  - We have screened the sequence of the 394 base pairs upstream of the main
      transcriptional start site of the promoter of the human parathyroid hormone (PTH)
      gene for well-known protein recognition motifs with the aim to identify potential
      positive or negative regulatory elements. Within this region we found a potential
      cAMP-response element (CRE) besides several other putative binding sites for
      transcription factors. We fused promoter regions that contain this element and
      extend beyond the transcription start site to an appropriate reporter gene (CAT)
      and transfected different cell lines with these constructs. Transient expression
      of the CAT gene from these hybrid genes could be shown to be significantly
      stimulated by forskolin or isoproterenol thus proving the responsiveness of the
      whole promoter region towards elevated cAMP levels. DNase I protection studies
      revealed protein binding around the putative CRE (PTH-CRE) and an adjacent CCAAT
      element. Gel retardation assays with the PTH-CRE as well as the well
      characterized CRE from the rat somatostatin promoter indicated specific binding
      of the same protein to both elements, although with a slightly reduced affinity
      of the PTH-CRE. Both of these elements were also able to confer cAMP
      responsiveness to a heterologous promoter.

PMID- 1977135
TI  - A Neurospora crassa ribosomal protein gene, homologous to yeast CRY1, contains
      sequences potentially coordinating its transcription with rRNA genes.
AB  - We have isolated and sequenced a Neurospora crassa ribosomal protein gene
      (designated crp-2) strongly homologous to the rp59 gene (CRY1) of yeast and the
      S14 ribosomal protein gene of mammals. The inferred sequence of the crp-2 protein
      is more homologous (83%) to the mammalian S14 sequence than to the yeast rp59
      sequence (69%). The gene has three intervening sequences (IVSs) two of which are
      offset 7 bp from the position of IVSs in the mammalian genes. None correspond to
      the position of the IVS in the yeast gene. Crp-2 was mapped by RFLP analysis to
      the right arm of linkage group III. The 5' region of the gene contains three
      copies of a sequence, the Ribo box, previously shown to be required for
      transcription of both 5S and 40S rRNA genes. We speculate that the Ribo box may
      coordinate ribosomal protein and rRNA gene transcription.

PMID- 1977136
TI  - The specific binding of nuclear protein(s) to the cAMP responsive element (CRE)
      sequence (TGACGTCA) is reduced by the misincorporation of U and increased by the
      deamination of C.
AB  - Point mutations in the cAMP-responsive element (CRE) of the rat somatostatin gene
      promoter/enhancer sequence (TGACGTCA) were used as a model for assessing the
      effect of uracil, deriving either from misincorporation during DNA synthesis (T--
      -U) or cytosine deamination (C----U), on the binding of sequence/specific
      regulatory proteins. The results show that the T----U conversion in both strands
      of the CRE palindromic sequence reduces its affinity for the CRE binding
      factor(s), suggesting the crucial role of the methyl group contributed by T for
      the correct recognition of the sequence. On the other hand, deamination of C in
      the CpG central dinucleotide (CpG----UpG) causes an increase of binding affinity
      which is further enhanced by the contemporary deamination in both strands. Then,
      both uracil misincorporation and cytosine deamination alter the binding to CRE
      sequence in vitro, suggesting that uracil, if not removed by uracil DNA
      glycosylase, could be dangerous for cellular functions.

PMID- 1977137
TI  - Identification of a common nonsense mutation in Japanese patients with type I
      adenine phosphoribosyltransferase deficiency.

PMID- 1977138
TI  - RFLP for the human prothrombin (F2) gene.

PMID- 1977139
TI  - A BstXI polymorphism at the D5S116 locus.

PMID- 1977140
TI  - Polymorphism at the FES locus detected by PFGE.

PMID- 1977141
TI  - A three allele TaqI polymorphism at TOP1 gene.

PMID- 1977142
TI  - Polymerase chain reaction (PCR) for detection of PstI polymorphism in the human
      PF4 gene.

PMID- 1977143
TI  - A PstI RFLP of the LACI gene.

PMID- 1977144
TI  - HindIII/EcoRI polymorphism in the GAA gene.

PMID- 1977146
TI  - TaqI polymorphism at the D6S91 locus.

PMID- 1977145
TI  - Identification of an insulin receptor exon 8 NsiI polymorphism using the
      polymerase chain reaction.

PMID- 1977147
TI  - A hypervariable RFLP within the ABR gene.

PMID- 1977148
TI  - A second hypervariable RFLP within the ABR gene.

PMID- 1977149
TI  - PCR detection of a 38 bp length variant in the COL1A2 gene.

PMID- 1977150
TI  - A HaeIII RFLP in COL1A1.

PMID- 1977151
TI  - [Gold salts in the treatment of bronchial asthma].
AB  - Gold salts are used mainly in the therapy of rheumatoid diseases. Thanks to their
      immunoregulative and antiinflammatory properties they may be used in treatment of
      chronic bronchial asthma. In order to study the efficacy of gold salts in such
      therapy the authors studied the effect of Solganal B (Schering) in 8 patients
      with chronic steroid dependent bronchial asthma. In 6 patients a clinical
      improvement was observed enabling to lower the steroid dose. Basing on this pilot
      study we believe that gold salts have an beneficial effect on the course of
      chronic bronchial asthma.

PMID- 1977152
TI  - Rapid sequence anesthesia induction for emergency intubation.
AB  - Emergency intubations are done for a variety of reasons in the emergency
      department (ED). In some patients, a rapid, controlled induction of anesthesia is
      useful to facilitate intubation and to reduce the complications of intubation.
      This is referred to a rapid sequence induction (RSI) in the anesthesia
      literature. Atropine, thiopental, fentanyl, diazepam, ketamine, vecuronium,
      succinylcholine, other drugs and their applications for RSI are described. The
      purpose of this article is to describe the use of RSI in the airway management of
      ED patients. Nineteen pediatric patients requiring emergency intubation were
      intubated using RSI with vecuronium and thiopental. Actual intubation difficulty
      using RSI was significantly less than the anticipated intubation difficulty
      without RSI. There were no complications caused by intubation or RSI that had a
      significant impact on patient outcome. We feel that a sedative in combination
      with vecuronium represents the most optimal means of achieving RSI in the ED
      setting. Although the induction of general anesthesia is best done by
      anesthesiologists, emergency physicians are often the most experienced physicians
      immediately available to manage an airway in a critical emergency. An objective
      protocol such as that described will make it easier for emergency physicians to
      perform this procedure when needed.

PMID- 1977153
TI  - [Clinical evaluation of cetirizine].
AB  - Efficiency of cetirizine--a new antihistaminic agent--was evaluated in 61
      patients with seasonal rhinitis in placebo-controlled double-blind trial.
      Patients were randomly divided into subgroups. Cetirizine significantly inhibited
      the symptoms of allergic rhinitis and conjunctivitis. Adverse reactions were
      similar to those of placebo. Increased clinical efficiency but also an increase
      in adverse reaction incidence were noted when the drug was administered in the
      evening and not in the morning. High efficacy of placebo is worth mentioning.
      Therefore, antihistaminic agents should be tested in placebo-controlled double
      blind trials.

PMID- 1977154
TI  - Asthma in primary care patients. Challenges and controversies.
AB  - Asthma varies in intensity, and patients must be treated as individuals to whom
      formulas do not apply. Often, the most difficult person to treat is the first
      time patient whose clinical course is unknown and whose response to medications
      is totally untested. Although exacerbating substances should be avoided whenever
      possible, medication unfortunately is still needed by most asthmatic patients. At
      present, the choice of initial medication is subject to individual physician
      preference; beta 2-adrenergic agonists, cromolyn sodium (Intal), theophylline,
      and aerosol corticosteroids are all acceptable as first-line treatment. Addition
      of a second, third, or fourth medication again depends on individual response and
      physician choice. Patients with asthma need to be educated regarding the nature
      of the disease and its almost total unpredictability. Equally important is a
      frequent review of medications and a willingness to alter regimens as situations
      require.

PMID- 1977155
TI  - Proceedings of the XXV National Congress of the Italian Society of Pharmacology.
      Taormina (Italy), October 14-18, 1990. Abstracts.

PMID- 1977156
TI  - Antihypertensive therapy.

PMID- 1977157
TI  - [Therapy changes and cost development in bronchial asthma. A 10-year
      retrospective study at the medical outpatient clinic of the Zurich University
      Hospital].
AB  - The changes that have taken place in asthma therapy during the past ten years and
      their consequences regarding costs were studied analyzing retrospectively 285
      clinical histories of asthmatics treated at the University Hospital Zurich in
      1977, 1982 and 1987. The following changes in the use of the five basic
      antiasthmatic drugs i.e. beta-adrenoceptor agonists, anticholinergic drugs,
      xanthines, glucocorticosteroids and antiallergic drugs were observed: In 1977 80%
      of asthmatics received beta-agonists, in 1987 90%. Conversely, parasympatholytics
      were rarely used: In 1977 in only 2%, in 1982 in 16% and in 1987 in 27% of
      patients. In 1987 xanthines were prescribed in only 50% of asthmatics whereas in
      1982 after the introduction of retarded preparations, these drugs were given to
      86% of patients. In 1977 only one-third of asthmatics received
      glucocorticosteroids; in 1987, however, three-quarters of them. Antiallergic
      drugs were prescribed in 1977 and 1987 in about 25% of the asthmatics, in 1982 in
      only 13%. Considering the form of application there was a significant trend
      towards metered aerosols. This was true for betamimetics, parasympatholytics and
      glucocorticosteroids. Fixed combinations and rectal applications of xanthines
      were substituted for retarded formulations. In 1977 one or two antiasthmatic
      drugs accounted for 75% of asthma therapy. In contrast, in 1987 60% of asthmatics
      received more than two antiasthmatic drugs. The dosages of salbutamol and
      beclomethasone increased significantly from 1977 to 1987. Other changes in
      dosages were not significant. The change in costs of antiasthmatic therapy
      revealed significant savings in regard of xanthines and antiallergic drugs.
      During the past ten years the overall costs of antiasthmatic drugs therapy
      remained the same despite more complex therapy.

PMID- 1977158
TI  - Expression of human asparagine synthetase in Saccharomyces cerevisiae.
AB  - Human asparagine synthetase was expressed in the yeast Saccharomyces cerevisiae.
      The identity of the expressed protein was confirmed by immunoblotting and in
      vitro enzymatic activity. The recombinant enzyme was shown to have both the
      ammonia- and glutamine-dependent asparagine synthetase activity in vitro. In
      contrast to overproduction in Escherichia coli, the expressed protein was found
      to be soluble in the yeast cell. Furthermore, expression in yeast made it
      possible to isolate non-degraded human asparagine synthetase which had also the N
      terminal methionine correctly processed. The yeast expression plasmid was
      constructed for optimal production of the recombinant enzyme. In addition, unique
      restriction enzyme sites that bracket the first five codons of the human
      asparagine synthetase gene were introduced. This will allow the use of
      oligonucleotide cassette mutagenesis to investigate the role of the N-terminal
      amino acids in asparagine synthetase enzymatic activity.

PMID- 1977159
TI  - Distribution and patterns of staining of Neu oncogene product in benign and
      malignant breast diseases.
AB  - Amplification of the Neu oncogene (c-erbB-2) has been reported by various
      researchers as a marker for poor clinical outcome in patients with breast cancer.
      We have performed immunohistochemical staining using a polyclonal antibody to the
      Neu oncoprotein on formalin-fixed material from normal breast, benign breast
      lesions, and 102 stage I node-negative breast cancers. Hybridization studies were
      also performed on 66 of the breast cancer cases. In the cancers 33% of cases
      showed positive staining of the in situ and invasive component, whereas only 25%
      of cases showed amplification of the Neu oncogene. The staining pattern in the
      tumor cells was cytoplasmic with plasma membrane accentuation. Focal positive
      cytoplasmic staining was noted in some cases of fibrocystic disease,
      fibroadenoma, and normal breast duct epithelium. Myoepithelial cells and smooth
      muscle of blood vessels also showed a positive reaction. This study shows that
      the Neu oncoprotein can be demonstrated on formalin-fixed material from normal,
      benign, and malignant breast lesions. In the breast cancers the differences in
      the number of cases showing amplification and those showing a positive
      immunohistochemical reaction could be due to increased transcriptional activity.
      It is possible that the node-negative patients whose tumors express the Neu
      oncogene may correspond to the group of patients who are expected to have a poor
      prognosis.

PMID- 1977160
TI  - Resting and activated subsets of mouse multipotent hematopoietic stem cells.
AB  - The fluorescent vital dye rhodamine 123 (Rh-123), which preferentially
      accumulates in mitochondrial membranes, can be used as a probe to indicate
      mitochondrial and hence cellular activity. In this study, mouse bone marrow
      hematopoietic stem cells were subdivided into Rh-123lo, Rh-123med, and Rh-123hi
      populations. The Rh-123lo (resting) population was significantly enriched in
      cells with a higher proliferative potential compared to the Rh-123hi (activated)
      population. The resting population exhibited a 20-fold greater ability to
      differentiate into splenic colony-forming units (CFU-S) relative to the activated
      population, whereas the activated population contained about 4-fold more day 13
      CFU-S on primary transfer relative to the resting population. The two populations
      produced morphologically distinct splenic colonies; however, the frequency and
      morphology of in vitro colonies were very similar. Only the resting population
      provided sufficient stem cells to transfer long-term hematopoietic repopulation
      to secondary recipient animals after lethal irradiation. On a single cell level,
      the resting and activated populations exhibited an equivalent ability to
      differentiate into lymphoid and myeloid progeny. These observations provide
      further insight into the heterogeneous nature of CFU-S and directly demonstrate
      that multipotent hematopoietic stem cells are heterogeneous with regard to their
      clonogenic capacities.

PMID- 1977161
TI  - cDNA cloning of a quail homeobox gene and its expression in neural crest-derived
      mesenchyme and lateral plate mesoderm.
AB  - We report here the cloning of a quail cDNA related to the Drosophila gene msh and
      to the mouse genes Hox-7 and Hox-7.1. For this reason we called this cDNA Quox-7.
      The amino acid homology of Quox-7 cDNA with the above mentioned genes is high
      (83%) for the homeobox and its 5'- and 3'-flanking sequences, and the homology is
      medium (43%) for another stretch of amino acids upstream of the homeobox;
      elsewhere the sequences of quail and mouse cDNAs have diverged significantly. In
      quail embryos of day 2-5, Quox-7 transcripts were found essentially in the
      ventral mesenchyme (neural crest-derived mesectoderm of the face and
      hypobranchial structures, somatopleure, and limbs) and also in a narrow
      dorsomedial band of cells of the superficial ectoderm and neural tube. This
      pattern is fundamentally similar to that reported for Hox-7/7.1, suggesting that
      the products of these genes play a similar role in the development of the
      different classes of vertebrates.

PMID- 1977162
TI  - Chronic antidepressant administration decreases the expression of tyrosine
      hydroxylase in the rat locus coeruleus.
AB  - Regulation of tyrosine hydroxylase expression by antidepressant treatments was
      investigated in the locus coeruleus (LC), the major noradrenergic nucleus in
      brain. Rats were treated chronically with various antidepressants, and tyrosine
      hydroxylase levels were measured in the LC by immunoblot analysis.
      Representatives of all major classes of antidepressant medication-including
      imipramine, nortriptyline, tranylcypromine, fluvoxamine, fluoxetine, bupropion,
      iprindole, and electroconvulsive seizures-were found to decrease levels of
      tyrosine hydroxylase immunoreactivity by 40-70% in the LC. Decreased levels of
      enzyme immunoreactivity were shown to be associated with equivalent decreases in
      enzyme mRNA levels. Antidepressant regulation of LC tyrosine hydroxylase appeared
      specific to these compounds, inasmuch as chronic treatment of rats with
      representatives of other classes of psychotropic drugs, including haloperidol,
      diazepam, clonidine, cocaine, and morphine, failed to decrease levels of this
      protein. The results demonstrate that chronic antidepressants dramatically
      downregulate the expression of tyrosine hydroxylase in the LC and raise the
      possibility that such regulation of the enzyme represents an adaptive response of
      LC neurons to antidepressants that mediates some of their therapeutic actions in
      depression and/or other psychiatric disturbances.

PMID- 1977163
TI  - Identification of a groES-like chaperonin in mitochondria that facilitates
      protein folding.
AB  - Mitochondria contain a polypeptide that is functionally equivalent to Escherichia
      coli chaperonin 10 (cpn10; also known as groES). This mitochondrial cpn10 has
      been identified in beef and rat liver and is able to replace bacterial cpn10 in
      the chaperonin-dependent reconstitution of chemically denatured ribulose-1,5
      bisphosphate carboxylase. Thus, like the bacterial homologue, mitochondrial cpn10
      facilitates a K(+)- and Mg.ATP-dependent discharge of unfolded (or partially
      folded) ribulose bisphosphate carboxylase from bacterial chaperonin 60 (cpn60;
      also known as groEL). Instrumental to its identification, mitochondrial cpn10 and
      bacterial cpn60 form a stable complex in the presence of Mg.ATP. Bacterial and
      mitochondrial cpn10 compete for a common saturable site on bacterial cpn60. As a
      result of complex formation, with either mitochondrial or bacterial cpn10, the
      "uncoupled ATPase" activity of bacterial cpn60 is virtually abolished. The most
      likely candidate for mitochondrial cpn10 is an approximately 45-kDa oligomer
      composed of approximately 9-kDa subunits. We propose that, like the protein
      folding machinery of prokaryotes, mitochondrial cpn60 requires a cochaperonin for
      full biological function.

PMID- 1977165
TI  - Chronobiology: its role in clinical medicine, general biology, and agriculture,
      Part A. Proceedings of the XIX international conference of the International
      Society for Chronobiology. Bethesda, Maryland, June 20-24, 1989.

PMID- 1977167
TI  - Chronobiology: its role in clinical medicine, general biology, and agriculture,
      Part B. Proceedings of the XIX international conference of the International
      Society for Chronobiology. Bethesda, Maryland, June 20-24, 1989.

PMID- 1977166
TI  - Infradian, notably circannual, cardiovascular variation gauging effect of
      intrauterine exposure to beta-adrenergic agonists.

PMID- 1977164
TI  - Loss of heterozygosity on chromosomes 17 and 18 in breast carcinoma: two
      additional regions identified.
AB  - The loss of heterozygosity (LOH) at specific regions of the human genome in tumor
      DNA is recognized as evidence for a tumor-suppressor gene located within the
      corresponding region of the homologous chromosome. Restriction fragment length
      polymorphism analysis of a panel of primary human breast tumor DNAs has led to
      the identification of two additional regions on chromosomes 17q and 18q that
      frequently are affected by LOH. Deletions of each of these regions have a
      significant correlation with clinical parameters that are associated with
      aggressive breast carcinomas. Previous restriction fragment length polymorphism
      analysis of this panel of tumors has uncovered several other frequently occurring
      mutations. LOH on chromosome 18q frequently occurs in tumors with concomitant LOH
      of loci on chromosomes 17p and 11p. Similarly, tumors having LOH on 17q also have
      LOH on chromosomes 1p and 3p. This suggests that certain combinations of
      mutations may collaborate in the development and malignant progression of breast
      carcinomas.

PMID- 1977168
TI  - Influence of ginseng saponin on the circadian rhythm of brain monoamine
      neurotransmitters.

PMID- 1977169
TI  - Mutagens and carcinogens in the diet. Proceedings of a satellite symposium on
      environmental mutagens. Madison, Wisconsin, July 5-7, 1989.

PMID- 1977170
TI  - A mammalian mutation system avoiding phenotypic selection: the RFLP/PCR approach.

PMID- 1977171
TI  - Neoadjuvant chemotherapy in invasive bladder cancer. Proceedings of an
      international workshop. San Francisco, May 19-20, 1989.

PMID- 1977172
TI  - Molecular biology and differentiation of megakaryocytes. Proceedings of the Third
      International Conference on Megakaryocytes: Megakaryocytes: Cellular and
      Molecular Biology. Dijon, France, July 23-27, 1989.

PMID- 1977173
TI  - Prostate cancer and testicular cancer. Proceedings of a consensus conference on
      prostate and testicular cancer. North Humberside, England, April 12-15, 1989.

PMID- 1977174
TI  - Treatment of post surgical adhesions. Proceedings of the First International
      Symposium. Phoenix, Arizona, September 15-17, 1989.

PMID- 1977175
TI  - Effects of four beta-adrenergic receptor antagonists on male rat sexual behavior.
AB  - Antihypertensive medication has been reported to cause serious sexual side
      effects in men. Frequently mentioned as causing sexual dysfunction are beta
      adrenergic receptor antagonists. The purpose of this study was to examine in
      detail the effects of beta blockers on adult male rat sexual behavior. Thirty
      minutes following a single subcutaneous injection of propranolol, pindolol,
      atenolol or labetalol, mating tests were conducted. The mixed beta 1- and beta 2
      adrenergic antagonists, propranolol and pindolol, profoundly inhibited male
      sexual behavior. At the 5 and 10 mg/kg doses, propranolol inhibited ejaculatory
      behavior to the extent that only 9.1 and 8.3% respectively showed the behavior
      while pindolol reduced this behavior to 36.4% (16 mg/kg). These drugs also
      adversely affected various parameters of behavior in a dose-dependent manner. The
      selective beta 1 antagonist, atenolol, had only minor effects and labetalol even
      less so at the doses tested. It was suggested that the strongly inhibitory
      effects of propranolol and pindolol on male rat sex behavior may well be due to
      their 5-HT1A antagonistic binding properties rather than their beta-antagonistic
      properties.

PMID- 1977176
TI  - Seizure promotion and protection by D-1 and D-2 dopaminergic drugs in the mouse.
AB  - Mice injected with pilocarpine (100-400 mg/kg plus 1 mg/kg methylscopolamine),
      picrotoxin (0.75-6 mg/kg) or strychnine (0.75-6 mg/kg) exhibited clonic or
      clonic/tonic convulsions. Pretreatment with the D-1 agonist CY 208-243 (0.375-1.5
      mg/kg) dose-dependently potentiated the convulsions elicited by 100 mg/kg
      pilocarpine, but had neither a convulsant nor anticonvulsant effect in mice
      receiving picrotoxin (3 or 6 mg/kg) or strychnine (0.75 or 1.5 mg/kg). This
      facilitatory effect of CY 208-243 was abolished by the D-1 antagonist SCH 23390
      (0.2 mg/kg). SCH 23390 by itself (0.05-0.8 mg/kg) dose-dependently protected mice
      against pilocarpine (400 mg/kg) seizures. Stimulating D-2 receptors with LY
      171555 (0.167-4.5 mg/kg) dose-dependently protected mice against seizure activity
      induced by pilocarpine, but neither protected nor sensitised mice given
      picrotoxin or strychnine. The neuroleptics haloperidol (1-4 mg/kg), sulpiride (10
      50 mg/kg), metoclopramide (1.25-6.25 mg/kg), thioridazine (0.5-2 mg/kg) and
      clozapine (0.5-2 mg/kg) had no effect on the seizure threshold to 100 mg/kg
      pilocarpine by themselves, although 10 mg/kg thioridazine and clozapine caused
      100% convulsions, possibly through a toxic action. When administered in
      conjunction with a minimally effective quantity of CY 208-243 (0.375 mg/kg),
      however, all five neuroleptics interacted synergistically with the D-1 agonist to
      promote convulsions to pilocarpine (100 mg/kg). No such interaction occurred
      between submaximally protective doses of the D-1 blocker SCH 23390 (0.05 and 0.2
      mg/kg) and a wide range of doses of the D-2 stimulant LY 171555 (0.167-4.5
      mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1977177
TI  - Chronic administration of typical, but not atypical neuroleptics induce
      persisting alterations in rest-activity cycles in rats.
AB  - The behavior of rats administered chronic neuroleptics was observed using an
      extremely sensitive, computerized device which detected any cage movements,
      thereby continuously monitoring even very small levels of activity. In the first
      experiment, it was found that normal rats have a strong rest-activity rhythm with
      a cycle length of 60-70 min, whereas rats which have been chronically
      administered either haloperidol (HAL) or fluphenazine (FLU) decanoate for 20
      months show a distinct lengthening of this cycle and that this effect persists
      long after cessation of drug injections. In a second experiment, it was further
      observed that these lengthened rest-activity cycles also occur when HAL is
      administered chronically either via osmotic minipumps or in the drinking water,
      but not following the chronic administration of two atypical neuroleptics
      (clozapine and raclopride). These findings suggest a useful new technique for the
      study of side-effects of neuroleptics in rats.

PMID- 1977178
TI  - Dopaminergic nature of acute cathine tolerance.
AB  - Cathine is a psychoactive constituent in the leaves of the Khat shrub which are
      habitually ingested for their stimulatory effects in many parts of the world.
      Rats were trained to discriminate the stimulus effect of intraperitoneally
      administered 4.8 mg/kg d-cathine and, once trained, administration of another
      Khat constituent, cathinone, was shown to produce cathine-like effects. This
      generalization to cathinone was dose-responsive when testing occurred 24 hr after
      vehicle administration, whereas prior administration of cathine resulted in a
      diminished discriminative response to subsequent cathinone administration
      possibly as a result of the development of acute tolerance. CGS 10746B, a
      compound that blocks presynaptic release of dopamine, significantly decreased
      rats' ability to discriminate cathine when it was administered 25 min prior to
      cathine testing and it reversed the acute tolerance observed when cathine was
      tested 24 hr after cathine administration. These results indicate that a
      previously reported acute tolerance effect to cathine after cathinone
      administration in cathinone-trained rats appears to be symmetrical in that there
      is acute tolerance to cathinone after cathine in these cathine-trained rats. The
      results with CGS 10746B would suggest that both the cathine-induced
      discriminative cue and cathine's ability to produce acute tolerance are mediated
      by presynaptic dopamine release.

PMID- 1977179
TI  - Benzodiazepine-induced impairment of matching-to-sample performance in humans.
AB  - The effects of benzodiazepines on a visual pattern matching-to-sample (MTS) task
      were examined in nine healthy male volunteers. The MTS task employed randomly
      generated checkerboard-like stimuli presented on a video display. The sample and
      two comparison stimuli were simultaneously presented. Nonmatching comparison
      stimuli were randomly generated to be 3.125, 6.25, 12.5, 25.0, 37.5, or 50.0
      percent different from the sample. Subjects responded on left or right button
      manipulanda to identify the matching comparison stimulus. The nonmatching
      stimulus condition was maintained constant for a 60-sec component and the
      percentage difference of the nonmatching stimuli was systematically varied across
      multiple components. The effects of triazolam (2.25-9.0 micrograms/kg) and
      lorazepam (7.5-45 micrograms/kg) were examined in a within-subjects, double
      blind, placebo-controlled study. Under placebo conditions, response rates and
      accuracy were a positive function of the nonmatching stimulus discriminability.
      Triazolam produced dose-related decreases in response rate at nonmatching
      stimulus conditions greater than or equal to 25%. Only the 9.0 micrograms/kg dose
      of triazolam decreased accuracy and this occurred across all nonmatching stimulus
      conditions. Lorazepam effects were qualitatively similar but less robust than
      those of triazolam.

PMID- 1977180
TI  - Dosing regimen differentiates sensitization of locomotion and mouthing to D2
      agonist quinpirole.
AB  - The study examines whether the order of administering 2 doses of quinpirole (0.5
      and 8 mg/kg) affects the development of behavioral sensitization, as measured by
      the amount of forward progression and mouthing. Results show that injection of
      the high dose greatly enhances the subsequent locomotor response to the low dose
      of quinpirole, but not vice versa. Mouthing activity is not influenced by order
      of administration but is significantly greater at the higher dose of quinpirole.
      The present findings are consistent with a hypothesis that locomotor
      sensitization involves down-regulation of a D1 tone normally inhibitory to D2
      locomotor activation.

PMID- 1977181
TI  - Decreased reactivity to anxiolytics caused by early protein malnutrition in rats.
AB  - In order to investigate whether early malnutrition causes lasting changes in the
      reactivity to anxiolytic drugs, rat dams during lactation (21 days) and pups
      after weaning until the 49th day of life were fed on 8% casein diet (M rats),
      while their well-nourished controls received 25% casein (W rats). From day 50 on
      all animals ate the same balanced diet. Experiments started on the 91st day. Rats
      deprived for 22 hours drank water containing either 1.8% or 2.7% sodium chloride
      for 30 min in a test chamber, total intake being measured. Dose-effect curves for
      diazepam (0.5-5.0 mg/kg, IP), as well as for the nonbenzodiazepine anxiolytics
      ipsapirone (0.5-5.0 mg/kg), ritanserin (0.05-1.0 mg/kg) and isamoltane (2.5-20.0
      mg/kg) were determined in M as well as in W rats. Diazepam and ipsapirone dose
      dependently released drinking suppressed by either salt concentration in W rats,
      but caused little or no effect in M rats. Ritanserin and isamoltane were
      ineffective in both groups. These and previously reported results show that early
      protein malnutrition markedly reduces anticonflict effects of anxiolytics,
      indicating long-lasting impairment of neuronal systems underlying emotional
      behavior.

PMID- 1977182
TI  - Overflow of catecholamine neurotransmitters to the circulation: source, fate, and
      functions.

PMID- 1977183
TI  - [26th Golnik symposium. Bronchial hyperreactivity. Proceedings].

PMID- 1977184
TI  - Nursing practice: physician assistants--certified.

PMID- 1977185
TI  - Sulphasalazine and the aminosalicylates in the treatment of inflammatory bowel
      disease.

PMID- 1977186
TI  - The source and significance of raised serum enzymes in rheumatoid arthritis.
AB  - Hepatobiliary dysfunction in rheumatoid arthritis has been suggested on the basis
      of raised serum activity of alkaline phosphatase, 5-nucleotidase, lactic
      dehydrogenase and gamma-glutamyl transferase, but a specific pathological lesion
      has not been demonstrated and serum transaminases and bilirubin are almost
      invariably normal. This paper reports a series of studies designed to determine
      the tissues of origin of the enzymes and offers an alternative interpretation of
      the enzymological findings. The results suggest that only alkaline phosphatase
      originates from the liver, while lactic dehydrogenase and 5-nucleotidase
      originate from synovial fluid polymorphs and synovial lining cells, respectively.
      Serum alkaline phosphatase may be induced by inflammatory mediators such as
      interleukin-1 because it correlates with the acute phase response. Serum lactic
      dehydrogenase is an integrated measure of polymorph lysis in all joints and
      offers a marker of joint inflammation more specific than measures such as the
      ESR. Levels of serum 5-nucleotidase provide information about the activity of the
      synovium. Finally, because hepatic necrosis does not normally occur, the
      transaminases may be used to monitor drug toxicity.

PMID- 1977187
TI  - Somatostatin release induced by gastrin-releasing peptide in man. Effect of
      proximal gastric vagotomy and cholinergic blockade.
AB  - The influence of intragastric pH on the basal release of somatostatin has been
      studied in healthy controls and in duodenal ulcer patients. In addition the
      somatostatin response to gastrin-releasing peptide infusion has been evaluated
      both regarding the effect of intragastric pH and the influence of vagal
      innervation and muscarinic blockade. No difference was found in basal blood
      levels, when changing the intraluminal pH, although a slightly higher basal
      somatostatin concentration was noticed in patients with duodenal ulcer disease.
      Neither proximal gastric vagotomy nor cholinergic blockade had any effect on
      basal somatostatin concentrations. GRP infused in stepwise increasing doses from
      20 pmol/kg/h to 400 pmol/kg/h induced a small but significant response. This
      effect of GRP was most evident, when the stomach was perfused with 0.1 M HCl. The
      small, somatostatin response to GRP infusion was not influenced by vagal
      denervation of the parietal cell area, neither by cholinergic blockade. Despite
      the previously observed effects of vagotomy and cholinergic blockade on gastrin
      release induced by GRP, a corresponding inverse effect on somatostatin is not
      apparent.

PMID- 1977188
TI  - Role of vasoactive intestinal polypeptide (VIP) and endogenous somatostatin on
      the secretion of epidermal growth factor (EGF): studies on duodenal tissue
      cultures.
AB  - Epidermal Growth Factor (EGF)-containing cells have been found in Brunner's
      glands in the same area where several regulatory peptides are released. The
      present study was aimed at testing the release and the regulation of EGF
      secretion from cultured duodenal biopsies obtained from healthy individuals by
      gastroscopy. The effects and the interaction of VIP and somatostatin on the
      hormone release were studied. Duodenal biopsies were cultured at 37 degrees C in
      Mc Coy's buffer, gassed with 95% O2 and 5% CO2. After 30 min, the culture medium
      was decanted for the measurement of the hormones by RIA. To measure the protein
      content, the tissue was then homogenized; EGF detected in the culture was 11.5
      ng/mg protein. The addition of VIP in the medium increased EGF mean levels to
      21.6 ng/mg protein (P less than 0.01). The biopsies thus obtained were cultured
      with anti-somatostatin antibodies to evaluate the influence of endogenous
      somatostatin on EGF secretion. The inclusion of anti-somatostatin antibodies
      increased the EGF levels to 41.2 ng/mg protein (P less than 0.01). The combined
      addition of anti-somatostatin antibodies and VIP in the culture caused a mean EGF
      increase significantly higher than the values obtained separately by VIP and
      somatostatin (P less than 0.01). In conclusion, we can suggest a triangular
      interaction model of EGF release, where the somatostatin seems to be the negative
      monitor of over-secreted VIP and EGF from the gut.

PMID- 1977189
TI  - [Ultrasonics in the diagnosis and monitoring of cryptorchism in children].
AB  - The diagnostic reliability of US was investigated in the study of cryptorchidism
      during a 9-month clinical and US trial performed on 52 children (mean age 4.3
      years). Cryptorchidism was unilateral in 44 cases (24 on the left side and 20 on
      the right side), and bilateral in 8 cases. Of 60 cryptorchid testes, 53-
      belonging to 45 of 52 patients--were located in the inguinal region (18 along the
      canal, 20 at the external ring, and 15 at the internal one); the others 7-
      belonging to the remaining 7 subjects--were found in an extra-inguinal region (4
      in paravesical location and 3 in the inferior abdomen). US confirmed 29
      undescended testes with clinical evidence in the inguinal region and identified,
      in the same area, 24 other testes which had been missed at clinical examination.
      In addition, US provided useful information as to both structure and volumetry of
      the gonads. On the other hand, US failed to provide reliable diagnostic results
      in the rare cases of pelvic and abdominal cryptorchidism, where precise testes
      localization was achieved by CT. US is the diagnostic technique of choice in the
      study of cryptorchidism (after clinical examination): the method is non-invasive
      and simple, has low cost and its use is widespread; moreover, US does not
      administer ionizing radiations. According to our experience, US had 88.3%
      diagnostic sensitivity as for undescended testes (53 of 60), and 100%
      specificity. In addition, US monitoring allowed clinical efficacy of therapeutic
      trials to be verified in 25 patients (17 sensitive to therapy): 16 of them were
      treated with human Chorionic Gonadotropin (hCG) and 9 with Luteinizing Hormone
      Releasing Hormone (LH-RH).

PMID- 1977190
TI  - Interleukins and T-cell development. The 31st Forum in Immunology. Proceedings.

PMID- 1977191
TI  - Differentiation of the active site of minaprine from that of phencyclidine in rat
      hippocampus.
AB  - The active site of minaprine (3-(2-morpholinoethylamino)-4-methyl-6
      phenylpyridazine) was studied by means of receptor binding and its effect on
      acetylcholine (ACh) release in rat hippocampus. [3H]Minaprine binding to the
      hippocampal membrane was inhibited by minaprine, 4-aminopyridine (4-AP) and
      phencyclidine (PCP) dose-dependently, whereas it was not inhibited by L-glutamate
      (L-Glu), N-methyl-D-aspartate (NMDA), 2-amino-5-phosphonovalerate (APV), 3-(3
      hydroxyphenyl)-N-(1-propyl)piperidine ((+)3-PPP) or ketamine. [3H]PCP binding was
      inhibited by PCP and APV in an extensively washed hippocampal membrane.
      Minaprine, however, failed to inhibit the [3H]PCP binding. [3H]3-(2
      carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) binding was inhibited by L
      Glu but not by minaprine. NMDA-evoked [3H]ACh release from the rat hippocampal
      slices was effectively inhibited by PCP. However, minaprine had no effect on the
      NMDA-evoked [3H]ACh release. Similar results were obtained from the study of
      [3H]ACh release in the striatum. These results suggest that minaprine exerts its
      action via the voltage-dependent K+ channel but not via the NMDA receptor-channel
      complex or sigma receptor.

PMID- 1977192
TI  - [Sensitive innervation of the nasal mucosa: current concepts].
AB  - Sensitive innervation of the nasal fossae by the trigeminal nerves is not a
      simple passive system of information transmission, but also plays a considerable
      role in nasal physiology. An antidromic transmission mechanism is in fact added
      to the conventional centripetal transmission, leading to the release of
      neurotransmitters (P-substance and C.G.R.P.) at the level of the neuronasal nerve
      endings. These substances can cause inflammation and vasodilatation (sub-mucosal
      and perivascular) in certain sites of the 5th nerve, and stimulate the second
      parasympathetic neurone at the level of the sphenopalatine ganglion. Such
      phenomena, when they extend beyond physiology, can be the source of local
      pathology (rhinitis) or loco-regional pathology (headaches).

PMID- 1977193
TI  - [Pain in the side].
AB  - In a 54-year-old patient who entered the hospital because of flank pain of the
      left side, a prevesicular urethral calculus was found. On further investigation
      hypercalcaemia and hypophosphataemia were detected, possibly indicating
      hyperparathyroidism. When an ultrasound of the abdomen was made to exclude
      hydronephrosis, a tumor in the pancreas was found. The result of the fine needle
      biopsy of this tumor showed a neuroendocrine tumor. The examination of
      neuroendocrine parameters was without any reference to an active secreting
      process. On suspicion of a multiple endocrine neoplasia, a MRI of the hypophysis
      was made which showed no adenomatous alterations. The examination of the
      neuroendocrine parameters were without any reference to an active secreting
      process of the hypophysis, too.

PMID- 1977194
TI  - [A comparative evaluation of the efficacy and tolerance of gold and D
      penicillamine preparations in patients with rheumatoid arthritis. II. The effect
      on the morphological indices of rheumatoid synovitis].
AB  - Morphological signs of rheumatoid synovitis have been analysed on the basis of
      130 puncture biopsies taken from 46 patients prior to the beginning and during
      parenteral therapy with auric preparations (crysanolom and myocrysin) and peroral
      administration of an auric preparation rhidaura and small doses of D
      penicillamine. The most marked morphological effect was reached in 1.5 years.
      With a favourable clinical effect all the preparations exhibited capacity for
      suppressing the following basic signs of rheumatoid synovitis: proliferative
      changes in the layer of synoviocytes, reaction of blast cells.

PMID- 1977195
TI  - [Method of treatment with salazopyridazine and diucifon].

PMID- 1977197
TI  - New perspectives on ofloxacin. Proceedings of a symposium. West Berlin, 16
      October 1989.

PMID- 1977196
TI  - Female urinary tract infection in primary health care: bacteriological and
      clinical characteristics.
AB  - Female patients with symptoms of urinary tract infection (n = 1136) were studied
      in primary health care with respect to (a) clinical symptoms as predictors of
      bacteriuria; (b) relation between aetiological agent and clinical picture,
      especially for P-fimbriated Escherichia coli; and (c) clinical findings in cases
      with 10(2)- less than 10(5) CFU/ml of E. coli. Prevalence of bacteriuria (greater
      than or equal to 10(5) CFU/ml) was 61%. Concurrence of urgency/frequency and
      dysuria, short duration of symptoms and hematuria increased the probability of
      bacteriuria and were also significantly more frequent among cases with low counts
      of E. coli (10(2) less than 10(5) CFU/ml in pure culture or mixed flora) than
      among cases with sterile urine, indicating an aetiological role of E. coli in
      many of those cases. Infections with P-fimbriated E. coli were as benign as the P
      fimbriae-negative. The rate of P-fimbriation was 29% in specimens containing
      greater than or equal to 10(5) CFU/ml of E. coli, 30% among specimens with less
      than 10(5) CFU/ml in pure culture and 10% in specimens containing less than 10(5)
      CFU/ml of E. coli in mixed culture. Patients infected with Klebsiella,
      Enterobacter or Proteus did not show a higher rate of previous urinary tract
      disease or anomalies.

PMID- 1977198
TI  - [The significance of gamma-glutamyltransferase in the evaluation of the results
      of chemotherapy of liver metastasis].
AB  - The serum concentration of gamma-glutamyltransferase (gamma-GT) was serially
      measured in 26 cancer patients undergoing chemotherapy for liver metastases. 20
      patients were studied retrospectively and 6 prospectively with emphasis on the
      first few days of cytostatic treatment. The gamma-GT determinations during the
      first days of treatment gave no indication of the prognosis of remission. Serial
      measurements during treatment do, however, serve to objectify the success of the
      chemotherapy. In most patients the gamma-GT concentrations paralleled the general
      condition as well as palpation and ultrasound examination of the liver. Direct
      interactions of cytotoxic drugs with gamma-GT could not be demonstrated. gamma-GT
      determinations are therefore of help in phase II studies in evaluating new drugs
      for their cytostatic activity against liver metastases.

PMID- 1977199
TI  - [Prevention of familial tumor diseases using genetic counseling and early
      diagnosis].
AB  - Several types of familial cancer can be prevented from progressing into an
      advanced stage through genetic counselling and regular medical control of persons
      at risk. Measures of secondary cancer prevention and their efficacy are described
      for retinoblastoma, MEN2 syndrome, familial colorectal carcinoma with (FAP) or
      without (HNPCC) pre-existing polyposis coli, dysplastic naevi syndrome, basal
      cell naevi syndrome and von Hippel-Lindau syndrome. The prevention of
      malignancies is promising primarily for the familial forms, since persons at risk
      are motivated to employ preventive measures, especially if they can be identified
      through DNA diagnosis and counselled with concrete information. The establishment
      of familial cancer registries should be considered which improve the continuous
      medical care for all family members, even in the case of a change of the family
      physician or a loss of contact.

PMID- 1977200
TI  - Human deathtraps for mosquitoes.

PMID- 1977201
TI  - Management of bile duct stones.

PMID- 1977202
TI  - [The role of biologically active substances in permeability changes in the blood
      vessels of patients with hemorrhagic fever with renal syndrome].
AB  - To judge the possible causes of the impairment of blood vascular permeability in
      hemorrhagic fever associated with the nephrotic syndrome (HFNS), 86 patients were
      examined over time for the blood content of histamine, serotonin and kallikrein.
      The patients were found to have hyperhistaminemia, hyperserotoninemia and
      activation of blood serum kallikrein, which attests to undoubted participation of
      these biologically active substances in the pathogenesis of HFNS.

PMID- 1977203
TI  - [The thrombocyte link in the hemostasis of patients with hemorrhagic fever with
      renal syndrome].
AB  - Altogether 38 patients (33 men and 5 women) suffering from grave and moderate
      hemorrhagic fever with nephrotic syndrome (HFNS) were examined. The hemolysate
      aggregation test and ADP were employed to explore the aggregation ability of
      platelets in those patients. Besides, measurements were made of the activity of
      the 3rd platelet factor in the plasma and serotonin content in each platelet. A
      considerable rise of the aggregation activity of platelets was established to
      take place in the oligoanuric and polyuric periods of HFNS. At the same time the
      increase in the blood of the 3rd platelet factor and lowering of serotonin in
      each platelet were noted. The role of platelet hyperaggregation in the
      pathogenesis of HFNS is discussed. The conclusion is made that such patients were
      in a prethrombotic state in the oligoanuric and to a lesser degree in the
      polyuric periods.

PMID- 1977204
TI  - [Vascular permeability, microcirculation and biologically active substances in
      patients with hemorrhagic fever with renal syndrome].
AB  - As many as 56 patients with associated hemorrhagic fever and the renal syndrome
      were examined for vascular permeability, microcirculation and blood plasma
      histamine, serotonin, kallikrein and prekallikrein. In all the disease periods,
      the majority of the patients (n-52) demonstrated a rise of vascular permeability
      for protein and liquid part of the plasma, with this being marked in particular
      in the oligoanuric period. Besides, significant perivascular and intravascular
      changes in microcirculation were noted in the oligoanuric and polyuric disease
      periods. It was established during examination of biologically active substances
      that the greatest shifts were experienced by the kinin system. Sometimes the
      content of kallikrein surpassed the control values more than 7-fold. Less
      pronounced changes were seen in blood plasma serotonin and histamine. A direct
      correlation was established between vascular permeability, microcirculation and
      the content of all biologically active substances explored by the authors. The
      strongest correlation was found to exist between the above parameters and the
      kinin system of blood plasma.

PMID- 1977205
TI  - [Current problems of pharmacotherapy--heart failure].
AB  - Cardiac muscle cell hypertrophy, hyperplasia of connective tissue, abnormal
      peripheral circulation and metabolic changes in the cardiac fibre and in the
      smooth muscle cell as a consequence of mechanic overload are described in
      variable proportions in heart failure. These changes in turn are essential
      factors for progression of the disease. Results of early drug intervention in
      patients with few or no symptoms suggest that decrease of mechanic overload by
      vasodilator therapy slows down the progression of the disease. In late stages,
      treatment with diuretics and vasodilators improves the symptoms and the outcome
      of heart failure. Diuretics alone and inotropic positive substances bring about
      some improvement of symptoms and maximal oxygen consumption, but they have no
      favourable effect on the outcome. Positive inotropic substances remain restricted
      to late forms of heart failure, in which they seem to ameliorate symptoms but
      have a rather unfavourable effect on the outcome. The role of diuretics, ACE
      inhibitors and digoxin is well defined. This is not the case for newer calcium
      channel blockers from the dihydropyridine group, of beta blockers, of
      phosphodiesterase inhibitors and of substances with partial beta agonist and
      partial beta blocking activity. These drugs must still be classified as
      experimental agents for the treatment of heart failure.

PMID- 1977206
TI  - [Drug therapy of acute myocardial infarction and unstable coronary syndrome].
AB  - Questionnaires were sent to 61 Norwegian hospitals treating acute coronary
      syndromes, and 90% replied. Thrombolytic drug treatment is now the routine when
      the history of chest pain is short and ischemia appears in ECG. Use of glyceryl
      trinitrate and beta blocking drugs varies considerably, as does the use of oral
      anticoagulants and platelet inhibitors. Practice also varies in unstable angina.
      However, a combination of aspirin, intravenous nitrate, and betablockers is
      common. Several treatment regimens have an uncertain scientific foundation. The
      varying practice reflects international scientific debate.

PMID- 1977207
TI  - [Drug therapy of acute coronary syndrome. Summary of a hearing arranged by the
      Norwegian Cardiologic Society and the Institute of pharmacotherapy].
AB  - Acute coronary syndrome is defined as unstable angina or acute myocardial
      infarction. A discussion on drug treatment of these conditions was arranged by
      the Norwegian Society of Cardiology and the Department of Pharmacotherapeutics,
      University of Oslo, soon after preliminary results of the GISSI II study were
      available. Relatively simple rules were agreed for the use of analgetics,
      nitrates and fibrinolytic agents. The last are used only after established
      myocardial injury. Consensus was also reached on the restricted use of calcium
      antagonists, inotropic agents and diuretics. There was disagreement concerning
      the dosage of heparin and the exact use of betablockers, aspirin, warfarin, ACE
      inhibitors, magnesium and antiarrhythmics.

PMID- 1977208
TI  - [The use of pharmacological criteria in the toxicological evaluation of
      veterinary drugs].
AB  - The toxicological evaluation of residues of veterinary drugs in foods of animal
      origin, which is done within the framework of the Netherlands Veterinary Drugs
      Act, is based on an EEC guide line in which, in addition to the clinical and
      analytical criteria, the requirements regarding the pharmacological and
      toxicological evaluation are laid down. In principle, this evaluation is based on
      classical toxicological criteria. As veterinary drugs have a specific
      pharmacological action, it is essential that these pharmacological effects should
      be in included in the toxicological evaluation in view of an adequate protection
      of public health. The selected starting point is that a pharmacological effect
      desired in a target animal is regarded as an undesirable effect in consumers. In
      this presentation, two examples are referred to, viz. the beta agonist
      clenbuterol and the beta-blocking agent carazolol; the approach is compared with
      a 'classical' toxicological evaluation. This shows that the acceptable daily
      intake in human individuals (ADI), based on pharmacological criteria is lower by
      a factor of approximately 50 than is the ADI on the basis of 'classical'
      toxicological criteria. This clearly illustrates the value of this approach in
      protecting the health of consumers.

PMID- 1977209
TI  - Nickel induced lipid peroxidation in the rat: correlation with nickel effect on
      antioxidant defense systems.
AB  - Lipid peroxidation (LPO) and alterations in cellular systems protecting against
      oxidative damage were determined in the liver, kidney and skeletal muscle of male
      F344/NCr rats, 1 h to 3 days after a single intraperitoneal (i.p.) injection of
      107 mumol nickel(II)acetate per kg body weight. At 3 h, when tissue nickel
      concentrations were highest, the following significant (at least, P less than
      0.05) effects were observed: in kidney, increased LPO (by 43%), increased renal
      iron (by 24%), decreased catalase (CAT) and glutathione peroxidase (GSH-Px)
      activities (both by 15%), decreased glutathione (GSH) concentration (by 20%),
      decreased glutathione reductase (GSSG-R) activity (by 10%), and increased
      glutathione-S-transferase (GST) activity (by 44%); the activity of superoxide
      dismutase (SOD) and gamma-glutamyl transferase (GGT), as well as copper
      concentration, were not affected. In the liver, nickel effects included increased
      LPO (by 30%), decreased CAT and GSH-Px activities (both by 15%), decreased GSH
      level (by 33%), decreased GSSG-R activity (by 10%) and decreased GST activity (by
      35%); SOD, GGT, copper, and iron remained unchanged. In muscle, nickel treatment
      decreased copper content (by 43%) and the SOD activity (by 30%) with no effects
      on other parameters. In blood, nickel had no effect on CAT and GSH-Px, but
      increased the activities of alanine-(ALT) and aspartate-(AST) transaminases to
      330% and 240% of the background level, respectively. In conclusion, nickel
      treatment caused profound cell damage as indicated by increased LPO in liver and
      kidney and leakage of intracellular enzymes, ALT and AST to the blood. The time
      pattern of the resulting renal and hepatic LPO indicated a possible contribution
      to its magnitude from an increased concentration of nickel and concurrent
      inhibition of CAT, GSH-Px and GSSG-R, but not from increased iron or copper
      levels. The oxidative damage expressed as LPO was highest in the kidney and
      lowest in the muscle, which concurs with the corresponding ranking of nickel
      uptake by these tissues.

PMID- 1977210
TI  - The interactions of cis-diamminedichloroplatinum with metallothionein and
      glutathione in rat liver and kidney.
AB  - The involvement of metallothionein (MT) in the nephrotoxicity of cis
      diamminedichloroplatinum (c-DDP) was investigated in rats using enzyme excretion
      and histology as indicators of renal damage. In addition, the effects of renal
      glutathione (GSH) depletion on the nephrotoxicity of c-DDP was assessed by
      organic anion transport in renal cortical slices. A dose of 6.0 mg c-DDP/kg body
      wt, i.p. was administered to rats either as a single injection of 6.0 mg/kg or as
      six daily injections of 1.0 mg/kg. Concentrations of platinum (Pt) after c-DDP
      injection in both dosing regimens were approximately 12 micrograms/g in kidney
      and 2 micrograms/g in liver. However, there were no increases in either hepatic
      or renal concentrations of MT after both series of c-DDP injections.
      Fractionation of kidney cytosols from c-DDP injected rats on Sephadex G-75
      columns revealed that 60-70% of cytosolic Pt was associated with proteins of high
      molecular weight and 15-20% of the Pt associated with the low molecular weight
      ligands. No discernable Pt peak was detected in the elution volume of MT.
      Pretreatment of rats with ZnSO4 increased both hepatic and renal concentrations
      of MT, but there was no Pt associated with the MT fraction after a subsequent
      injection of c-DDP. Small increases in the urinary excretion of the lysosomal
      enzyme, N-acetyl-beta-D-glucosaminidase and two brush border enzymes, alkaline
      phosphatase and gamma-glutamyltranspeptidase were observed 2 and 3 days after a
      single injection of c-DDP (6.0 mg/kg body wt, i.p.). Urinary creatinine excretion
      decreased by 50% 1 day after c-DDP injection and continued to decrease for the
      next 2 days. On the third day after c-DDP treatment, a small but significant
      decrease in body weight was also observed in the c-DDP injected animals.
      Pretreatment with Zn did not alter the c-DDP-induced enzymuria or renal tubular
      damage but slightly attenuated both the decrease in creatinine excretion and the
      loss in body weight. Uptake of the organic anion, p-aminohippuric acid (PAH) was
      reduced at 12 and 24 h after c-DDP injection. Reduction of tissue GSH
      concentrations by pretreatment with buthionine sulfoxime (BSO), resulted in only
      a slight increase in the c-DDP-induced inhibition of PAH uptake at 24 h after c
      DDP injection. These results suggest that, in rats, neither MT nor GSH appear to
      play major roles in the binding or nephrotoxicity of c-DDP.

PMID- 1977211
TI  - Techniques applicable for purifying Chironex fleckeri (box-jellyfish) venom.
AB  - A survey of several techniques to isolate a purified lethal factor from the
      tentacles of Chironex fleckeri was completed. Heterologous band patterns were
      obtained from specific eluates after gel filtration, ion exchange, immunoaffinity
      and hydrophobic chromatography. SDS-PAGE revealed a dense band at 24,000 mol. wt
      in many of these fractions. Isoelectric focusing of the crude venom resulted in
      considerable loss of activity but indicated significant purification in the
      fractions having a pI of 5.2-6.8. These fractions were also immunologically
      active against sera from a convalescing post-evenomation patient. The primary
      difficulties encountered in jellyfish venom purification are the lack of
      stability and the tendency of the active toxins to adhere to each other and to
      various support matrices.

PMID- 1977212
TI  - Purification and pharmacological characterization of peptide toxins from the
      black mamba (Dendroaspis polylepis) venom.
AB  - This paper reports the purification of 28 different peptides from the venom of
      the snake Dendroaspis polylepis. These peptides represent 99% of the total
      peptide fraction in the venom. The 14 most cationic peptides form a structurally
      and functionally homogeneous group of analogs of the most abundant dendrotoxin
      toxin I (DTXI). They recognize antibodies raised against DTXI as well as brain
      membrane binding sites corresponding to K+ channels that are sensitive to DTXI
      and the bee venom peptide MCD. Similarly to DTXI these 14 peptides induce
      convulsions after intracerebroventricular injections in mice and induce GABA
      release from synaptosomes. However, members in this iso-DTXI family differ widely
      in their affinity for the DTXI/MCD receptors and in their contractility promoting
      action on intestinal smooth muscle. The 14 other less cationic peptides do not
      interact with the DTXI receptor or with DTXI antibodies and they do not evoke
      GABA release. Their targets seem to be essentially of a peripheral nature. Half
      of them contract guinea pig ileum. In this group of toxins there might be new
      tools to study membrane excitability.

PMID- 1977213
TI  - Flow cytometric detection of jellyfish venom induced cytotoxicity.
AB  - Crude venoms of three poisonous jellyfish produce membrane depolarization as
      determined by the loss of fluorescence intensity of 3,3'-dipentyloxacarbocyanine
      iodide loaded cells measured by flow cytometry. This method for detecting
      jellyfish cytotoxicity was reproducible and more sensitive than mouse lethality
      assays.

PMID- 1977214
TI  - Effects of S-(1,2-dichlorovinyl)-L-cysteine on the transport of para
      aminohippurate ion in renal plasma membrane vesicles.

PMID- 1977215
TI  - Dichlorovinyl cysteine (DCVC)-induced enzymuria in mice: potential application in
      occupational toxicology?

PMID- 1977216
TI  - Cytotoxicity of nephrotoxic glutathione-conjugated halohydroquinones.

PMID- 1977217
TI  - Nephrotoxicity of quinol/quinone-linked S-conjugates.

PMID- 1977218
TI  - Differences in ischemia-induced accumulation of amino acids in the cat cortex.
AB  - It is well established that excitatory amino acid neurotransmitters are
      extensively liberated during ischemia and that they have neurotoxic properties
      contributing to neuronal injury. To study changes in the liberation of excitatory
      and other amino acids during cerebral ischemia, we measured their extracellular
      concentrations and related them to blood flow levels and electrophysiologic
      activity (electrocorticogram and auditory evoked potentials) before and for up to
      2 hours after multiple cerebral vessel occlusion in 14 anesthetized cats. Blood
      flow levels between 0 and 43 ml/100 g/min were reached. Concentrations of the
      excitatory amino acid neurotransmitters increased most (aspartate 10-fold,
      glutamate 30-fold, and gamma-aminobutyric acid 300-fold compared with control
      values) below a blood flow threshold of 20 ml/100 g/min. The total power of the
      electrocorticogram and the amplitude of the auditory evoked potentials were
      affected below the same blood flow threshold. In contrast, concentrations of the
      nontransmitter amino acids taurine, alanine, asparagine, serine, and glutamine
      increased 1.5-5-fold as blood flow decreased, while concentrations of the
      essential amino acids phenylalanine, valine, leucine, and isoleucine did not
      change during cerebral ischemia. The great increases in concentrations of the
      excitatory amino acid neurotransmitters below a blood flow threshold close to
      that for functional disturbance is in accordance with the role of these amino
      acids in ischemic cell damage. Their release at blood flow levels compatible with
      cell survival and the increase in their concentrations with severity and duration
      of cerebral ischemia imply that excitotoxic antagonists may have potential as
      therapeutic agents.

PMID- 1977219
TI  - Antibody-induced rejection of pig proislet xenografts in CD4+ T cell-depleted
      diabetic mice.
AB  - Reversal of diabetes in mice was achieved following in vivo depletion of host
      CD4+ T cells and transplantation of xenogeneic fetal pig proislets (pancreatic
      islet precursors). These procedures resulted in xenograft tolerance since
      established pig proislet xenografts were not rejected by antipig antibodies
      produced in the host, and rejection was not induced following the administration
      of donor major histocompatibility complex--specific pig lymphocytes. Proislet
      xenografts were rejected following the administration of donor MHC-specific hyper
      immune antipig PBL serum raised in normal mice. Although established proislet
      xenografts in anti-CD4-treated mice are sensitive to antibody-mediated
      destruction, such hosts are unable to produce an antibody response that leads to
      graft rejection. The study indicates that the mechanism of preventing xenograft
      rejection by anti-CD4 treatment in vivo involves not only initial CD4+ T cell
      depletion but also quantitative and/or qualitative modulation of a CD4+ T cell
      dependent antibody response. As a consequence, an apparent state of xenograft
      tolerance is produced.

PMID- 1977221
TI  - Proceedings of the Seventh Scientific Congress of the Transplantation of
      Australia and New Zealand. March 28-30, 1990, Canberra, Australia.

PMID- 1977220
TI  - Allograft rejection in athymic nude rats by transferred T cell subsets. II. The
      response of naive CD4+ and CD8+ thoracic duct lymphocytes to an isolated MHC
      class I disparity.
AB  - Athymic PVG-rnu/rnu (RT1c) rats were grafted with skin bearing isolated MHC
      disparities 7-14 days in advance of cell transfer. The ability of naive CD4+ or
      CD8+ thoracic duct lymphocytes to induce rejection was assessed by adoptive
      transfer of one or both T cell subsets into nude recipients bearing congenic
      PVG.r1 (MHC class I-only disparity, Aa) or PVG.r19 (class I and II-only
      disparity, Aa B/Da) skin grafts. Recipients of purified CD4+ TDL always rejected
      r19 allografts, whereas CD8+ TDL were ineffective against this class I + II
      difference. Neither the injection of CD4+ TDL nor CD8+ TDL alone resulted in
      destruction of r1 skin grafts. However, rejection of r1 tissue was observed in
      63% of cases (19/30) when both CD4+ and CD8+ TDL were present in the nude
      recipients. Rejection of r1 skin was also induced in some recipients when CD8+
      TDL were transferred 8 weeks in advance of CD4+ TDL. In contrast, sequential
      transfer in the reverse order apparently induced tolerance in the CD4+ population
      -i.e., surviving r1 skin grafts on 8 week CD4+ T cell-reconstituted nude
      recipients were not rejected following the subsequent transfer of CD8+ TDL. We
      conclude that CD4+ T cells were required for rejection of both class I and class
      II differences. In the presence of a class II difference, CD4+ T cells function
      autonomously to initiate both the inducer and effector stages of rejection. When
      the disparity is confined to class I, CD8+ T cells are required (probably at the
      effector stage) but are dependent on CD4+ T cells for help. There was no evidence
      of CD4+ effector T cells that could recognize class I directly within the graft.

PMID- 1977222
TI  - Characterization of the rat CD26 antigen.

PMID- 1977223
TI  - Comparison of serological class II typing with DNA-DR and DNA-DQ typing of kidney
      donors and recipients.

PMID- 1977224
TI  - Fourth Congress of the European Society for Organ Transplantation. November 1-4,
      1989, Barcelona, Spain. Proceedings.

PMID- 1977225
TI  - HLA-DR typing of renal allograft patients and donors by DNA-RFLP: correlation
      with pretransplant serotyping.

PMID- 1977226
TI  - [Treatment of unstable angina pectoris. A questionnaire study].
AB  - Questionnaires about therapy in unstable angina pectoris were sent to 63 Danish
      medical departments and were answered by 52 departments (82.5%). Nitroglycerin is
      commonly used but only in half of the departments is Nitroglycerin administered
      intravenously. Calcium-receptor-blockers are used in more departments (65%) than
      beta-receptor-blockers (35%) (p less than 0.05). Five departments use
      thrombolytic therapy along local guidelines. All recommend aspirin as prophylaxis
      against thrombosis and 63% recommend the therapy to be continued for life. An
      exercise test is always performed during hospital stay in 1/3 of the departments
      while the rest of the departments often wait till after the patient has been
      discharged. The estimate of frequency of coronary angiography varied
      considerably: from less than 5% to 100%. The frequency of coronary angiography
      was stated to be higher in Copenhagen and Aarhus (median 50%, interval 10-100%)
      than in the rest of the country (median 15%, interval less than 5-75%) (p less
      than 0.01).

PMID- 1977227
TI  - [European organization for research and treatment of cancer. Melanoma Cooperative
      Group meeting, Copenhagen, 26-28, April 1990].

PMID- 1977228
TI  - [Obesity and diabetes as side-effects of beta-blockers].
AB  - Overweight and obesity may develop in individuals with genetically determined low
      resting energy expenditure. Drugs are among the recognised precipitating factors.
      The obesity promoting impact of beta-blockers is, however, less well known.
      Resting energy expenditure, and thermogenesis induced by stimuli such as meals,
      cold and heat exposure, stress and anxiety, have a facultative component mediated
      by the sympathoadrenal system through catecholamines working on beta
      adrenoceptors. Treatment with beta-blockers reduces the facultative thermogenesis
      by 50-100 kcal/d, which corresponds to the weight gain of 2-5 kg/year reported in
      clinical trials. Treatment with beta-blockers also results in insulin resistance,
      which may aggravate existing diabetes and elicit diabetes in predisposed
      patients. Overweight and obesity are frequently complicated with hypertension and
      angina pectoris, which are often treated with beta-blockers. Obesity is
      associated with a defective sympathetic activity, and treatment with beta
      blockers may further reduce facultative thermogenesis and promote weight gain.
      The consequence may be aggravation of hypertension, insulin resistance and other
      atherogenic factors. The causal therapy of android overweight and obesity
      complicated with diabetes or hypertension is a sufficient weight loss. If
      pharmacological treatment is inevitable, combined treatment with diuretics and
      ACE-inhibitors are most appropriate.

PMID- 1977229
TI  - Hyperprolactinaemia--a clinical study with special reference to long-term follow
      up, treatment with dopamine agonists, and pregnancy.

PMID- 1977230
TI  - Membrane fluidity and lipid composition of rat testicles in experimental
      cryptorchidism.
AB  - Membrane fluidity and lipid composition of rat testis in experimental bilateral
      cryptorchidism were studied. Membrane fluidity measured by fluorescence
      anisotropy of diphenylhexatriene decreased on the 3rd day of intraabdominal
      fixation, at an early stage of cryptorchidism. Lipid composition of testicular
      membrane was changed drastically by the treatment, and time-dependent changes
      were observed during the course of the experiment. Cholesterol content increased
      significantly, but phospholipid content was not affected by the treatment. The
      ratio of cholesterol to phospholipids increased significantly. Fatty acid
      moieties of phospholipids varied during the course of the experiment. The ratio
      of unsaturated to saturated fatty acids decreased on the 3rd day. These changes
      indicated a different physical state of cryptorchid membranes from normals, and
      the changes may be involved in the pathophysiology of cryptorchidism.

PMID- 1977231
TI  - Testicular development following unilateral orchiopexy measured by a new
      orchiometer.
AB  - Of 170 patients having undergone orchiopexy for unilateral cryptorchid testes, 90
      responded to our inquiry. Testicular size was measured in 55 patients using an
      accurate and practical orchiometer (punched-out orchiometer) developed in our
      department. In boys under ten years of age (prepubertal), testicular development
      was minimal, and the operated on and contralateral testes were not significantly
      different. With the onset of puberty, both testes enlarged, and no significant
      differences were observed. However, by age fourteen the side operated on was
      significantly (p less than 0.05) less well developed than the contralateral
      testis. No difference was detected clinically between the operated on and
      contralateral testes when the contralateral testis was less than 10 mL in volume.
      When the contralateral testis was greater than 15 mL, however, a significant
      difference was detected both statistically (p less than 0.05) and clinically. The
      findings suggest limited prospects for the development of testes that are
      operated on at puberty.

PMID- 1977232
TI  - A newly established human acute lymphoblastic leukemia cell line with
      characteristics of the earliest B-cell maturation.
AB  - A new human acute lymphoblastic leukemia (ALL) cell line, designated HBL-3, was
      established from the bone marrow of a patient with non-T-ALL. The HBL-3 cell line
      expressed B4 (CD 19), BA-1 (CD 24) and HLA-DR antigens, but not surface
      immunoglobulin (SIg) or cytoplasmic immunoglobulin (CIg). The cell line lacked
      the common acute lymphoblastic leukemia antigen (CALLA) and antigenic markers
      characteristic of T-cell and myeloid cell lineages. The HBL-3 cells had
      structural rearrangements of both the homologous chromosome 9s, including a
      translocation with chromosome 1 which has been reported in a patient with common
      ALL. The cell line had rearranged immunoglobulin heavy chain genes but retained
      germ-line kappa light chain genes and germ-line T-cell receptor beta- and gamma
      chain genes. The HBL-3 cell line was strongly positive for terminal
      deoxynucleotidyl transferase (TdT). These findings indicate that the HBL-3 cell
      line is derived from the earliest B-cell committed to B-cell lineage.

PMID- 1977233
TI  - Immunohistochemical studies of S-100 protein alpha and beta subunits in adenoid
      cystic carcinoma of salivary glands.
AB  - Immunohistochemical studies were performed to explore the distribution of S-100
      protein and its alpha, beta subunits in 76 adenoid cystic carcinomas (ACC) of the
      salivary glands. Histopathologically. ACC was divided into cribriform, tubular,
      basaloid and trabecular types which could be mixed in the same tumor. S-100
      protein was usually positive in tumor cells forming cribriform structures; foci
      of strongly positive tumor cells were also distributed in the luminal layer of
      tubular structures, and in areas transitional between cribriform and tubular
      patterns. S-100 alpha staining was confined to some tumor cells in cribriform
      areas, to luminal tumor cells in tubular structures and to few tumor cells in
      basaloid structures. S-100 beta reaction was usually localized to luminal
      surfaces in a fine granular pattern in tubular and microtubular structures in a
      distribution somewhat similar to that in the normal salivary gland. Great
      heterogeneity in the immunohistochemical distribution of S-100, S-100 alpha and S
      100 beta proteins was found in the various histologic types of ACC and the
      pattern was different from that seen in pleomorphic adenomas. It is possible that
      the ACC tumor cells positive for S-100 protein may be closely related to true or
      modified myoepithelial cells.

PMID- 1977234
TI  - Morphological findings in the liver of diabetic rats after intraportal
      transplantation of neonatal isologous pancreatic islets.
AB  - Morphological (light microscopical, immunohistological and electron
      microscopical) findings in the recipient liver of rats with streptozotocin
      induced diabetes, obtained 9 months after intraportal injection of neonatal
      isologous pancreatic islets, are described and their significance discussed. The
      results support the assumption of active ingrowth of nonmyelinated nerve fibers
      into the islet isografts. The hepatocytes surrounding the islet isografts contain
      -obviously owing to the influence of unusually high and locally variable
      concentrations of insulin--a focally increased number of enlarged mitochondria,
      abundant glycogen and a smaller amount of neutral fat droplets. Furthermore,
      hepatocytes and cells looking like hepatocytes (hepatocyte-like cells) with
      typically structured cytoplasmic beta (insulin) granules were found bordering the
      islet isografts. These results could be interpreted as an expression of
      artificial or nonartificial fusion of beta cells with hepatocytes, i.e. formation
      of hybrid cells ("in vivo hybridization"). Alternatively, they might reflect
      insulin uptake and storage in the hepatocytes. In addition, these findings
      suggest that contact between neonatal islet tissue and liver tissue could be a
      trigger for the in vivo transformation (modulation) of differentiated cells of
      similar embryonic development in the adult organism.

PMID- 1977235
TI  - Sex-related incidence of tubular metaplasia in Bowman's capsule of aging rats.
AB  - Although chronic progressive nephropathy and proteinuria are well-known to affect
      old laboratory rats, the occurrence of tubular metaplasia of Bowman's capsule
      (TM) in aging rats has received little attention. We report here that old (24-26
      months) male, but not female Sprague-Dawley rats show a high incidence of TM
      which is significantly (P less than 0.01) correlated with the levels of
      glomerular sclerosis and intracellular deposits of iron in the tubular
      epithelium. The incidence of these changes was not correlated with serum
      testosterone levels, which showed a significant age-related reduction in males.
      The reported findings suggest that the aging male Sprague-Dawley rat is a useful
      animal model to investigate the pathogenesis of TM and related morphologic
      changes in hematuric humans.

PMID- 1977236
TI  - Demonstration of bacterial antigen in macrophages in experimental pyelonephritis.
AB  - The immunomorphological characteristics of interstitial macrophages with PAS
      positive granules were studied in experimental Escherichia coli pyelonephritis in
      rats, using an anti-E. coli antibody. Immunohistochemical, immunoelectron
      microscopical, as well as light- and electron microscopical findings were
      compared at twelve time points between 2 days and 13 weeks after infection.
      Macrophages with PAS-positive granules were present in the inflammatory
      infiltrates from the 7th day. The granules were phagolysosomes, filled
      predominantly with myelin figures. The myelin figures originated mainly from the
      constituents of the bacterial wall and reacted with the anti-E. coli antibody
      even 13 weeks after infection. The storage of bacterial residues with preserved
      antigenic structures for several weeks after infection indicates disturbed
      phagolysosomal elimination of the bacterial substances in the PAS-positive
      macrophages. In the formation of macrophages with PAS-positive granules,
      lysosomal overloading with large amounts of bacteria and cell debris is assumed,
      leading to consumption of the lysosomal enzymes, consequent incomplete breakdown
      and retention of the bacterial residues.

PMID- 1977237
TI  - Mouse epidermal cell renewal after topical treatment with different
      concentrations of the epidermal peptide pyroGlu-Glu-Asp-Ser-GlyOH.
AB  - Earlier work has shown that epidermal cells contain a peptide, pyroGlu-Glu-Asp
      Ser-GlyOH, that induces a moderate but long-lasting inhibition of epidermal cell
      proliferation when given at low (picomol) doses ip in vivo and in vitro. In the
      present study, the epidermal pentapeptide was applied topically to the back skin
      of hairless mice at different concentrations and in a water-miscible cream. A
      single topical application of either high (0.25% wt/wt) or low (0.004% or 0.02%
      wt/wt) doses of the pentapeptide was followed by oscillations in epidermal DNA
      synthesis and G2-M cell flux (mitotic rate). In general, epidermal cell
      proliferation was inhibited during the first 10-day period after treatment with
      the two lower doses, while the highest concentration of pentapeptide (0.25%)
      stimulated epidermal cell proliferation. In spite of the effects on epidermal
      cell proliferation the size of the epidermal cell population in the treated area
      (number of nucleated cells and epidermal thickness) showed no corresponding
      alterations. The results could imply that the epidermal pentapeptide modifies
      epidermal cell proliferation and terminal differentiation in such a way that the
      two are balance with each other.

PMID- 1977238
TI  - Isolation and long-term cultivation of human tonsil follicular dendritic cells.
AB  - Highly purified follicular dendritic cells (FDC) were isolated from human tonsils
      and cultivated for up to 150 days. The cell separation method employed produced
      pure aggregates (FDC-clusters) composed of FDC and germinal center lymphoid
      cells, useful for the analysis of the relationship between these two cell types
      and of the behavior of FDC in culture. During the first few days of culture,
      lymphoid cells located between FDC extensions survived better than those which
      were free or partly covered by FDC. After 6 days, the lymphoid population
      degenerated and only the FDC survived. The unique antigenic pattern of FDC
      (positive for HLA-DR. DRC-1, CD14b, CD21, CD23, CD35) disappeared within a few
      days of culture. Recombinant interferon-gamma exerted a positive effect either on
      retaining HLA-DR expression or on the reexpression of these antigens by FDC. HLA
      ABC antigens were traced until the 10th day and desmosomal junctions until the
      14th day. Subsequently, FDC presented peculiar features, including oval and
      rhomboid shapes, one to ten nuclei, fine amoeboid extensions, stress fibers and a
      radical dense zone in their cytoplasm. FDC possessed actin, tubulin and vimentin,
      but neither desmin nor cytokeratin. After 40 days of culture, FDC enlarged and
      were covered with abundant membrane extensions. Even when kept as long as 150
      days in vitro. FDC did not proliferate in any of the culture conditions employed.

PMID- 1977239
TI  - [International meetings on physical medicine in the FRG].

PMID- 1977240
TI  - A profile of California's physician assistants.

PMID- 1977241
TI  - Pharmacokinetic characteristics of bornaprolol in healthy volunteers.
AB  - 1. Six young male volunteers received five single doses of bornaprolol, i.v. (20
      mg) and orally (120, 240, 480, 960 mg) administered at 2-week intervals. Plasma
      concentrations of bornaprolol and its conjugated metabolite were determined by
      gas chromatography. 2. After i.v. administration, plasma bornaprolol levels were
      detectable over 8 h, and mean values were 60 l/h for total clearance (C1), 207 l
      for volume of distribution (V beta), 2.6 h for elimination half-life (t1/2 beta).
      After oral administration, plasma bornaprolol levels were detectable over 24-48
      h, and mean values of pharmacokinetics parameters were 60 l/h for C1, 1500 l for
      V beta, 20 h for t1/2 beta. Maximum plasma concentrations and area under the
      plasma concentration-time curve increased in a non-dose-dependent manner. 3. The
      glucuronide conjugate appeared in the blood within 5-10 min and its plasma level
      greatly exceeded bornaprolol concentrations. The mean value of the ratio of the
      metabolite AUC/parent product AUC was 14 after i.v. administration and 13-21
      following oral administration, depending on dose. The AUC for the metabolite did
      not increase proportionally with oral doses. 4. Bornaprolol is principally
      eliminated after metabolism. This process did not increase with increasing oral
      doses and bioavailability seemed to decrease inversely with oral dose.

PMID- 1977242
TI  - [Psychopharmaceutic agents in the family practitioner's hands].

PMID- 1977243
TI  - [Peptic ulcer--advances in drug therapy].

PMID- 1977244
TI  - [Alpha-adrenergic control of coronary circulation and left ventricular function
      during exertion].
AB  - Sympathetic activation is responsible for a striking inotropic and chronotropic
      response as well as for important coronary hyperemia during exercise. However the
      exact role of the coronary and myocardial alpha adrenergic receptors during
      sympathetic activation is not well defined. It is well accepted that coronary
      artery smooth muscle contains both alpha-1 and alpha-2 adrenergic receptors which
      elicit a vasoconstrictor response upon neurogenic and humoral stimulation. It
      seems however paradoxical that coronary vasoconstriction should occur in
      conditions of increased myocardial oxygen consumption such as during exercise. On
      the other hand, presynaptic alpha-2 receptors have been identified at the
      sympathetic nerve endings which, when stimulated by the locally released
      norepinephrine, will attenuate further norepinephrine release through a negative
      feed-back mechanism. A possible regulatory role of this mechanism for the left
      ventricular and coronary flow response during exercise has not been established.
      The major goal of this work was to define the exact role of alpha adrenergic
      receptors for the regulation of cardiac function and coronary circulation during
      exercise. Left ventricular function, coronary circulation, myocardial metabolism
      and catecholamine release were analysed during standardized treadmill exercise in
      conscious chronically instrumented dogs, prior to and following the
      administration of different alpha receptor blockers with different affinities for
      the different subtypes of alpha receptors. Three series of experiments were
      conducted to clarify: 1. the role of postsynaptic alpha receptors for the
      regulation of coronary blood flow during exercise, 2. the role of presynaptic
      alpha receptors for the regulation of left ventricular function during exercise,
      and 3. the role of postsynaptic alpha receptors for the regulation of transmural
      myocardial blood flow distribution during exercise. Dogs were instrumented with a
      solid state pressure transducer in the left ventricular cavity, a Doppler flow
      probe around the left circumflex coronary artery, and silastic catheters in
      aorta, left atrium and coronary sinus. 2-3 weeks after surgery the dogs were
      subjected to standard treadmill exercise. Simultaneous and continuous
      measurements were performed of heart rate, left ventricular systolic and end
      diastolic pressure, LV dP/dt/P, mean arterial pressure, late diastolic coronary
      vascular resistance, regional myocardial blood flow, myocardial oxygen
      consumption and plasma catecholamines. In the first series of experiments,
      coronary blood flow and myocardial oxygen consumption were analyzed in 15
      conscious dogs at rest and during exercise prior to and following IV
      administration of phentolamine (1 mg/kg) or prazosin (0.5 mg/kg).(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 1977245
TI  - Schizophrenia: a neurotransmitter imbalance syndrome?

PMID- 1977247
TI  - [Barodontology and barotrauma in human dentition].

PMID- 1977246
TI  - Hypervariable regions of DNA for parentage testing and individual identification.
AB  - Four kinds of DNA probes that recognize hypervariable regions (HVR) were studied
      for parentage testing and individual identification. Allele frequencies and their
      confidence intervals among unrelated Japanese individuals were obtained.
      Codominant segregation of the polymorphism was confirmed in family studies. Two a
      priori probabilities were calculated for each HVR locus: the exclusion
      probabilities for an alleged father/mother/child trio and for an alleged
      parent/child duo, and the probabilities of matching of genotypes of two unrelated
      individuals or two siblings. The ease of availability of the probes and their
      highly discriminating polymorphic patterns mean they could be very useful for
      forensic purposes.

PMID- 1977248
TI  - Proceedings of the IVth Trilateral Conference on Yeasts. Sarospatak, Hungary,
      July 24-28, 1989. Abstracts.

PMID- 1977249
TI  - Increased levels of immunoreactive leukotriene B4 in blister fluids of bullous
      pemphigoid patients and effects of a selective 5-lipoxygenase inhibitor on
      experimental skin lesions.
AB  - The immunoreactive leukotriene B4 (i-LTB4) and i-LTC4 content in the blister
      fluids of patients with bullous pemphigoid (BP) was determined by
      radioimmunoassay. Their amounts significantly exceeded those noted in superficial
      dermal burn patients and those in the fluids of suction blisters produced on
      normal human skin. When either BP blister fluids or BP-IgG from the patient sera
      were injected into guinea pig skin, neutrophil and eosinophil infiltrates were
      produced in the dermis. In addition, the dermis was noted to undergo marked
      edematous change. A single oral administration of a selective inhibitor of 5
      lipoxygenase 1 hr before the intracutaneous injection of BP-IgG was found to
      significantly inhibit cell infiltrates. Furthermore, the inhibitor partly
      suppressed dermal epidermal separation. On the basis of these results. LTB4 and
      LTC4 appear to be generated in the skin lesions of BP, the former attracting
      granulocytes to the dermis and the latter, causing exudation.

PMID- 1977250
TI  - Enzyme release from cultured human melanoma cells.
AB  - The lysosomal enzyme beta-hexosaminidase and the melanocyte specific enzyme
      tyrosinase were examined in human melanoma cell cultures. The beta-hexosaminidase
      activity of the medium was approximately 40% of the total cellular activity after
      24 h, while after 48 h the activity in the medium was twice that of the cells.
      The tyrosinase activity in the medium was 5% and 19% of the total cellular
      activity after the 24 h and 48 h incubation, respectively. The low level of
      lactate dehydrogenase activity in the medium after 24 as well as 48 h of
      incubation indicated that the release of beta-hexosaminidase and tyrosinase was
      not due to membrane injury. The data suggest, that 1) beta-hexosaminidase may be
      a candidate for tumor markers in malignant melanoma, and 2) the tyrosinase
      activity found in sera of melanoma patients may be due, at least partly, to
      enzyme release by living cancer cells.

PMID- 1977251
TI  - Isolation of soluble tyrosinase from human melanoma cells.
AB  - In the human melanoma cell tyrosinase exists in a membraneous and a soluble form.
      The membraneous enzyme has an N-terminal amino acid sequence identical to that
      predicted from a human c-DNA clone by Kwon et al.. The soluble form has now been
      isolated by a technique mainly based on the trypsin resistence of the enzyme and
      the use of hydrophobic interaction chromatography. The specific dopa oxidase
      activity of the soluble enzyme was 300 mumol/min x mg protein. On isoelectric
      focusing the enzyme was found in at least ten bands, pI between 3.8-4.6. The
      molecular weight was found to be 53,000 D. The N-terminal amino acid sequence was
      the same as that found in the membrane bound form of the enzyme, i.e. the protein
      maps at the c-albino locus.

PMID- 1977252
TI  - Initial hyperproliferation and incomplete terminal differentiation of cultured
      human keratinocytes from lesional and uninvolved psoriatic skin.
AB  - Human epidermal keratinocytes (KCs) were isolated from lesional and from
      uninvolved skin of 8 patients with chronic plaque-like psoriasis and from the
      normal skin of 8 healthy volunteers. Primary KC cultures, grown on 3T3 cell
      feeder layers, were examined over a period of 4 weeks and their plating
      efficiency, colony growth area, DNA synthesis and ultrastructural cell
      differentiation were evaluated. Psoriatic KCs formed colonies one day earlier
      than non-psoriatic controls and proliferated faster during the first 2 weeks, as
      assessed by the mean colony growth area and 3H-thymidine incorporation. After 4
      weeks, however, no significant differences were observed between the in vitro
      proliferation parameters of normal and psoriatic KCs. At the ultrastructural
      level, cultures of lesional psoriatic KCs consisted of more cell layers with
      adherent transitional cells and incomplete formation of cornified envelopes, even
      after 4 weeks, while KCs from uninvolved psoriatic skin were characterized by a
      transient delay of in vitro maturation. These results indicate that the
      characteristic hyperproliferation of psoriatic KCs may only be maintained over a
      short period of primary culture, whereas defective terminal differentiation of
      lesional psoriatic KCs was maintained throughout the culture period.

PMID- 1977253
TI  - Nickel in intercellular fluid. Comparison between nickel-allergic patients and
      controls.
AB  - Twelve non-atopic women with nickel allergy and allergic contact dermatitis
      (pompholyx type) were compared with matched controls without any known allergy.
      Intercellular fluid was obtained by the suction blister technique, and sufficient
      material for analysis was available from 10 women from each group. The median
      nickel concentration was 16 nmol/l in the patient group and 39 nmol/l in the
      controls (p less than 0.02). Calculated dietary intake of nickel during the week
      before examination was similar in the two groups, but the fluid intake was larger
      in the control group. Urine was collected in the morning before examination by 11
      women in each group; the nickel concentrations showed no difference between the
      two groups. These observations suggest that cellular uptake of nickel in
      sensitized patients may be sufficient to influence the kinetics of nickel in the
      body.

PMID- 1977254
TI  - Patients with dermatitis herpetiformis, acne, psoriasis and Darier's disease have
      low epidermal zinc concentrations.
AB  - Zinc concentration was determined in epidermis, papillary dermis and serum in
      patients with dermatitis herpetiformis, acne or psoriasis and in two small groups
      of patients with ichthyosis vulgaris and Darier's disease. Except in ichthyosis
      vulgaris the zinc level in epidermis was decreased in all these disorders. The
      mean serum zinc concentration was, however, significantly decreased only in men
      with dermatitis herpetiformis. There was no correlation between the concentration
      of zinc in epidermis or dermis and that in serum. The decreased epidermal zinc
      concentration indicates that many of the patients have a zinc deficiency in spite
      of a "normal" serum zinc value. Supplementation of zinc might therefore be of
      value in patients with these disorders.

PMID- 1977255
TI  - Dermatomyositis-like syndrome in X-linked hypogammaglobulinemia. Case-report and
      review of the literature.
AB  - A case of dermatomyositis-like syndrome is described in a 19-year-old man with a
      history of Bruton's hypogammaglobulinemia. Although the patient had central
      nervous-system manifestations (seizures), no echovirus was isolated in the
      cerebrospinal fluid, in contrast to previously reported cases. Data for our case
      and the 15 cases previously reported in the literature are reviewed. HLA typing
      of our patient revealed the presence of HLA B8 and DR3, which seems to play a
      major role in juvenile dermatomyositis.

PMID- 1977256
TI  - Regional variations in analgesic efficacy of EMLA cream. Quantitatively evaluated
      by argon laser stimulation.
AB  - The effect of EMLA cream (a eutectic mixture of local analgesics) applied for 30,
      60, 90 and 120 min on the forehead, cheek, back, cubital fossa, and dorsum of the
      hand was studied. Analgesic onset, efficacy and duration were evaluated by
      sensory and pain thresholds to laser stimulation measured before, and 5, 60, 120,
      and 180 min after the cream was removed from the skin. Cutaneous blood flow was
      measured and found to be 4-5 times as high on the face as on the other locations.
      On the forehead the analgesic efficacy decreased with increased application time.
      For all other locations, efficacy increased with increasing application time. On
      the back, onset was rapid and sufficient analgesia could be obtained, but
      analgesias began to wane immediately after removal of the cream. In the cubital
      fossa and on the hand, onset was tardy, and efficacy continued to increase for 60
      min after cream removal, followed by a slow decline. Blood flow, epidermal and
      dermal thickness are important factors affecting onset, efficacy and duration of
      EMLA analgesia.

PMID- 1977257
TI  - Exacerbation of porokeratosis during etretinate therapy.
AB  - Four patients with disseminated superficial porokeratosis (DSP) were treated with
      the oral aromatic retinoid etretinate. Using the standard dosage of 1 mg/kg/day,
      3 patients showed exacerbation of cutaneous lesions 4-6 weeks after initiation of
      treatment. Because of additional severe generalized itching and discomfort in all
      patients, treatment had to be discontinued. The clinical exacerbation correlated
      with a significant increase in the lymphohistiocytic dermal infiltrate beneath
      the cornoid lamella. In our experience the use of etretinate triggered the
      exacerbation of porokeratotic lesions with associated side effects showing that
      their use is not necessarily of benefit as previously reported.

PMID- 1977258
TI  - Antipruritic effect of oral cyclosporin A in atopic dermatitis.
AB  - The effect of ten days' treatment with cyclosporin A, 5 mg/kg/day, in 10 adults
      with atopic dermatitis was investigated using a double-blind, randomized, placebo
      controlled, cross-over design. Evaluation was based on itch recording, clinical
      scoring and immunohistochemical examination of skin biopsy specimens. Cyclosporin
      A significantly reduced the itch intensity, the eczema score and the consumption
      of topical hydrocortisone. A significant decrease in serum magnesium and in the
      total number of blood eosinophils was seen. No other laboratory abnormalities
      were observed. In lesional skin, Cyclosporin A induced a relative decrease of
      CD3+ T cells in 5/10 patients, of HLA-DR+ cells in 6/10, and of interleukin-2
      receptor positive (CD25+) cells in 4/10. However, these changes in phenotype
      expression did not seem necessary for itch relief. Relapse of clinical symptoms
      was seen within 2-30 days of completion of the Cyclosporin A course. The
      mechanism of the antipruritic effect remains unclear, but the present findings
      may support the hypothesis that 'pruritogenic cytokines', whose production is
      inhibited by Cyclosporin A, may be important in the pathogenesis of itch in
      atopic dermatitis.

PMID- 1977259
TI  - Epidemiology of genital herpes infections in Sweden.
AB  - The epidemiological pattern of genital herpes infections was studied by
      evaluating virus isolations and serological results based on samples collected
      from Goteborg and Malmo, the two largest urban areas of southern Sweden. 1087
      strains of herpes simplex virus isolated from cases of clinical herpes in
      Goteborg during the period 1980 to 1987 were evaluated for type relatedness. It
      was found that type 1 constituted 10% of the overall number of strains isolated
      with insignificant variation from year to year and type 1 and 2 occurred in same
      proportions in men and women. The HSV type 2 specific seroprevalence in 1158
      pregnant women from Malmo during the years 1973, 1979, 1987 and 1989 was studied.
      A significant increase in prevalence figures was noted from 1973 to 1987. The age
      related seroprevalence of 1211 men and 531 women in Goteborg suggested a 5 to 10%
      increase per 5-year period. Generally, higher prevalence was observed in women
      than in men, and about 10% of the men and 20% of the women might have been
      asymptomatically infected.

PMID- 1977260
TI  - Cryosectioning of hair follicles. An improved method using liquid nitrogen
      conduction freezing.
AB  - Horizontal sectioning of scalp biopsies is especially useful in hair diseases
      characterized by a reduction of follicles in size or number. Horizontal
      sectioning using standard cryo-microtomes is hampered by the differences in
      cutting properties between hair follicles and fatty tissue, resulting in loss of
      topography. We report a simple, inexpensive method to temporarily cool the
      specimen to an appropriate temperature by means of a conduction system using
      liquid nitrogen. Immunohistological methods such as immunofluorescence and
      immunoperoxidase techniques can be applied without restrictions.

PMID- 1977261
TI  - In vitro effects of testosterone, dihydrotestosterone and estradiol on cell
      growth of human hair bulb papilla cells and hair root sheath fibroblasts.
AB  - The influence of testosterone, dihydrotestosterone (each 10 ng/ml up to 300
      ng/ml) and estradiol (0.2 ng/ml up to 10 ng/ml) on the growth behaviour (cell
      count, [3H]thymidine uptake, cell doubling time) of subcultured human hair bulb
      papilla cells and hair root sheath fibroblasts was studied. Papilla cells and
      root sheath fibroblasts were isolated by microdissection from the same anagen
      hair follicles obtained from biopsies of androgen-sensitive scalp regions in 6
      healthy male subjects. Dihydrotestosterone and testosterone concentrations above
      30 ng/ml significantly reduced the growth of both cell types; lower doses had no
      effect. Estradiol had no distinct influence on the growth curves of either cell
      type up to 10 ng/ml, whereas higher concentrations significantly increased the
      growth of both cell types as shown by [3H]thymidine uptake. Papilla cells reacted
      more sensitively than root sheath fibroblast to dihydrotestosterone and
      testosterone, as shown by the growth curves, [3H]thymidine uptake, and cell
      doubling time.

PMID- 1977262
TI  - Reversal of andro-genetic alopecia in a male. A spironolactone effect?
AB  - This 73-year-old white male has been bald since the age of 28. He developed nonA
      nonB-induced liver cirrhosis and had been treated with spironolactone for the
      last 6 years. For the last 3 months, his hair had started to regrow over the
      scalp. This might be related to the antiandrogenic effect of spironolactone.

PMID- 1977263
TI  - Preputial ectopic sebaceous glands mimicking molluscum contagiosum.
AB  - The authors describe a 12-year-old boy with a peculiar presentation of preputial
      papular lesions similar to molluscum contagiosum. Histopathologic investigation
      revealed the presence of a sebaceous gland opening directly onto the surface and
      hyperplasia of the epithelium.

PMID- 1977264
TI  - Urticarial vasculitis occurring in association with visceral malignancy.
AB  - This is a report of a solitary patient who had urticarial vasculitis and an
      adenocarcinoma of the colon. Urticarial vasculitis has not been described in
      association with malignancy. It is considered that tumor-associated immune
      complexes might have been involved in the pathogenesis of the vasculitis.

PMID- 1977265
TI  - Erythropoietic protoporphyria. The problem of a suitable screening test.
AB  - Erythropoietic protoporphyria (EPP) is characterized by increased red cell
      protoporphyrins and is included in the differential diagnosis of children
      presenting with photosensitivity. In the past 20 years, using the traditional
      solvent extraction qualitative screening test for blood porphyrins, the diagnosis
      of EPP had been missed in 9 out of 10 patients but recently, using fluorescence
      microscopy of erythrocytes, no patients with EPP have been missed. All 14
      patients in Northern Ireland known to have EPP were recalled and it was found
      that fluorescence microscopic determination was positive in all cases. We
      recommend fluorescence microscopy as the screening test of choice for the
      detection of increased red cell porphyrins.

PMID- 1977266
TI  - Vitamin D metabolism in psoriasis before and after phototherapy.
AB  - Epidermis plays a major role in vitamin D synthesis and is a target tissue for
      1,25 (OH)2 vitamin D, which could be involved in abnormal proliferation and
      differentiation of psoriatic keratinocytes. We investigated plasma calcium,
      phosphorus, alkaline phosphatases, parathyroid hormone, 25 (OH) D, 24,25 (OH)2 D
      and 1,25 (OH)2 D in 15 control subjects and 20 psoriatic patients before and
      after 3 weeks of phototherapy (UVB or PUVA). Before irradiation, all parameters
      were similar in psoriatics and controls, except for serum phosphorus (lower in
      psoriasis p less than 0.01). After phototherapy, P rose to normal values in
      psoriatic patients; 25 (OH) D and 24,25 (OH)2 D were dramatically increased by
      UVB (but not by PUVA) in psoriatic patients as well as in controls; 1,25 (OH)2 D
      was unmodified in controls but was significantly increased in psoriasis. Since
      1,25 (OH)2 D has been reported to be an effective treatment for psoriasis, the UV
      induced increase in 1,25 (OH)2 D could account for the beneficial effect of
      phototherapy in psoriasis.

PMID- 1977267
TI  - Pseudoporphyria and sunbeds.
AB  - Five cases of pseudoporphyria with recurrent blistering and skin fragility
      especially of the hands are described. Porphyrin studies were normal. The
      histopathological investigations in three of these cases showed subepidermal
      bullae consistent with porphyria cutanea tarda. All patients had considerable
      sunbed exposure before symptoms appeared. One patient was taking naproxen, a weak
      photosensitizer.

PMID- 1977268
TI  - A possible case of drug-induced familial pemphigus.
AB  - Two sisters developed pemphigus vulgaris and pemphigus erythematosus within 3
      years. The diagnosis was confirmed by clinical, histologic and immunofluorescent
      antibody studies. One of the sisters experienced a common cold before the
      pemphigus developed and displayed a positive macrophage migration inhibition
      (MIF) test to a combination drug compounded of paracetamol, caffeine,
      chlorpheniramine maleate and phenylephrine HCl, which she had received 2 weeks
      prior to the appearance of the cutaneous lesions. It is suggested that her
      pemphigus was triggered by the drug. Although the patient had a strong genetic
      and familial predisposition to pemphigus, her clinical symptoms did not become
      evident until they were activated through an exogenous factor, namely, the
      causative drug. This case offers an example of a possible interaction between
      endogenous, genetic factors, and exogenous, triggering factors in the development
      of full-blown disease.

PMID- 1977269
TI  - Haemophilus influenzae type b cellulitis of the lower extremity in a non
      immunocompromised elderly patient.
AB  - An 83-year-old non-immunocompromised man who developed Haemophilus influenzae
      cellulitis on his lower left leg is described. H. influenzae type b was isolated
      by conventional bacteriological cultures from one blood culture and from a
      cutaneous blister fluid aspirate, and identified within the dermis by
      immunofluorescence on a punch biopsy of lesional skin. Evolution was
      characterized by a slow healing during appropriate systemic antibiotherapy, and
      absence of any significant increase in antibodies to the capsular polysaccharide
      of H. influenzae type b.

PMID- 1977270
TI  - Changes in renal biopsies during low dosage cyclosporin treatment.

PMID- 1977271
TI  - Oral hairy leukoplakia.

PMID- 1977272
TI  - Neuron-specific enolase-immunoreactive fibres in uremic patients.

PMID- 1977273
TI  - Immunologic mechanism in sulphasalazine-induced agranulocytosis.

PMID- 1977274
TI  - Pharmacological modulation of transmitter activity in Alzheimer brains--an
      experimental model.

PMID- 1977275
TI  - Brain monoamines and their metabolites in dementia.

PMID- 1977276
TI  - Growth hormone-releasing hormone and growth hormone-releasing peptide as
      potential therapeutic modalities.

PMID- 1977277
TI  - Interrelationship of somatostatin and growth hormone-releasing hormone in the
      genesis of the rhythmic secretion of growth hormone.

PMID- 1977278
TI  - Somatostatin and its physiological significance in regulating the episodic
      secretion of growth hormone in the rat.
AB  - Somatostatin (SS) is a powerful inhibitor of growth hormone (GH) secretion both
      in vitro and in vivo, and is generally regarded as having a negative influence on
      GH secretion and growth. In the conscious rat, the GH secretory pattern, the
      response to repeated injections of GH-releasing hormone (GHRH), and the feedback
      mechanism by which GH regulates its own release are all sexually dimorphic and
      probably reflect a sexually dimorphic pattern of SS release. Prolonged infusions
      of SS initially block GHRH-induced GH release but responses begin to break
      through with time. Withdrawal of SS induces a rebound release of GH in vivo,
      largely dependent on the release of endogenous GHRH. Prolonged exposure to
      intermittent infusions of SS in normal female rats produces a paradoxical growth
      response by inducing regular peaks of GH secretion whereas continuous infusions
      of SS do not. This response is GH-dependent, and is not due to other effects of
      SS since intermittent infusions of SS do not increase growth in dwarf rats which
      are deficient in pituitary GH. The sex differences in GH secretion are also
      reflected in the expression of several GH-dependent liver enzymes, one of which,
      carbonic anhydrase III, responds to manipulations of the endogenous secretory
      pattern by SS in both normal and dwarf rats, and appears to be sensitive to
      differences in basal, rather than peak, GH levels.

PMID- 1977280
TI  - Mechanisms of sodium homeostasis: sodium and water excretion in mammals-
      haemodynamic, endocrine, and neural mechanisms. Proceedings of a symposium.
      Copenhagen, July 5-7, 1989.

PMID- 1977281
TI  - Silent myocardial ischemia: a critical appraisal. An international round table.
      Tel Aviv, December 3-7, 1989. Proceedings.

PMID- 1977279
TI  - Pulsatile growth hormone secretory pattern: autofeedback regulation and effects
      on growth factors.

PMID- 1977282
TI  - [Plate osteosynthesis of the femur in patients with multiple and mono-trauma].
AB  - In multiple trauma patients successful treatment of femur shaft fractures depends
      more on timing of osteosynthesis than on choosing a specific type of fracture
      stabilization. Because of theoretical and practical reasons early osteosynthesis
      within 24 to 48 hours seems to be advantageous. In our experience it led to a
      significant decrease in complications. However, concomitant thorax trauma
      mandates special consideration. The two fatalities in our study belonged to this
      subgroup. With adequate indication for therapeutic intervention, correct
      operative technique and consideration of the patient's general status good
      results can be expected with every type of fracture treatment available (external
      fixation, plate fixation, intramedullary nailing).

PMID- 1977283
TI  - [Treatment results and indications for surgery in subtrochanteric femur fractures
      during growth].
AB  - A series of 29 subtrochanteric femoral fractures in children and adolescents
      treated during the last twenty years is presented. Primary osteosynthesis was
      done in five, secondary osteosynthesis in eleven patients. Ten patients were
      treated by an unilateral external fixator, two by a DC-plate, two by
      intramedullary nails, one by a Rushpin and one by cerclage wires. There were no
      deep infections. 13 patients were treated conservatively. Axial deviations
      resulted from conservative therapy in 9 of 11 patients, from osteosynthesis in
      one of 15 patients. One third of both series showed rotatory malalignment.
      Spontaneous corrections of axial deviations during growth can only be expected in
      small children to a small amount. In the average, operatively treated children
      had a positive leg length difference of one to two centimeters, whereas
      conservative treatment mostly resulted in equal leg lengths, but few patients
      showed differences from -4cm to +1 cm. Rotation and leg length seem to be more
      important for the clinical outcome than axial deviations of less than 20 degrees.
      Except in cases of severe concomitant injuries subtrochanteric fractures of the
      femur do not present an indication for primary osteosynthesis. If fracture
      reduction is not achieved by conservative means during the first four days
      osteosynthesis by DC-plates is recommended.

PMID- 1977284
TI  - [The efficiency of various osteosynthesis techniques in fractures of the greater
      trochanter].
AB  - Experimental investigations concerning the strength of different common used
      techniques of osteosyntheses of the greater trochanter were carried out on 22
      cadaver femora. The maximal loading values were measured and analysed. Loading of
      the tilted femur corresponding to the bended-hip position decreased the tolerable
      loading values essentially.

PMID- 1977285
TI  - [Isolated rupture of the anterior distal syndesmosis. A diagnostic problem].
AB  - Referring to one case of isolated rupture of the distal tibiofibular syndesmosis
      the mechanism of accident, findings, differential diagnosis and therapy of this
      rare and isolated injury are discussed. The clinical symptoms are not clear. In
      diagnostics the arthrography of the upper ankle joint proves very good. For the
      protection of suture of the ligament the hook according to Engelbrecht seems to
      be superior to the positioning screw.

PMID- 1977286
TI  - [Syndesmosis transfixation screw].
AB  - Instability of the distal tibia-fibular joint necessitates the implant of a
      fibular tibial transfixation screw. The screw should be placed 2 cm above the
      anterior syndesmosis. The angle of insertion is 30 degrees upwards from dorsal in
      relation to the frontal plane. If tibiofibular stability cannot be maintained
      following anatomical reconstruction of the fibula the transfixation screw must
      engage the medial tibial cortex. This is imperative, since the transfixation
      screw cannot withstand the biomechanical forces during motion and bearing of load
      if the screw penetrates only three corticals.

PMID- 1977287
TI  - [Radio-ulnar bridge callus following osteosynthesis of forearm fractures].
AB  - 137 patients with forearm fractures and internal plate fixation were investigated
      for postoperative radio-ulnar synostosis. 10 patients (7.3%) developed such a
      complication, 7 after complete, 3 after either ulnar or radial lesion. Of 73
      patients with complete forearm fractures, 50 had separate incisions, and
      developed radio-ulnar synostosis only secondary to severe soft tissue injury. Of
      12 other patients, by contrast, who were operated on for radial and ulnar plate
      fixation via one common incision (Boyd's approach), synostosis occurred in 5.
      After isolated ulnar fractures in 32 cases, synostosis was seen in two cases - in
      one after severe soft tissue injury, in the other after a modified Boyd's
      approach. Only one patient with isolated and open fracture of the radius
      presented later with radio-ulnar synostosis.

PMID- 1977288
TI  - [One- or two-step management (with external fixator) of severe pilon-tibial
      fractures].
AB  - Pilon tibiale fractures with significant joint involvement (AO-classification
      B2/3 and C2/3) are considered one of the most unfavourable injuries of the lower
      extremity. It was possible for follow-up examinations to be performed on 50
      patients with this injury pattern from the years 1984 to 1988. Primary plate
      osteosynthesis is primary blamed for causing a high infection rate. Remaining
      functional losses, uneven joints, defective positionings and early arthrosis are
      not avoidable with either a one step or a two step approach. The infection rate
      could be significantly lowered through a two step approach with primary
      stabilization through an external fixator, without having to accept further
      disadvantages. An early change of procedure in suitable cases between the second
      and third week guarantees an internal osteosynthesis with the best possible
      anatomic reposition of articular surface and axes. In chosen cases an end
      treatment is possible with an external fixator. The road is open for a primary
      arthrodesis of irreparably damaged articular surfaces.

PMID- 1977290
TI  - [Correct imaging of the shoulder joint in 2 planes (a.p. and axial) using curved
      or flexibly packed roentgen film].

PMID- 1977289
TI  - [Augmentation surgery of the anterior cruciate ligament using a carbon fiber
      band. Results of follow-up studies of 21 cases. I. (clinical aspects)].
AB  - Clinic and radiological follow-ups after implanting unidirectional carbon fibres
      in 21 cases (17 recent traumas, 1 older trauma and 3 chronic instabilities)
      approximately 34 months after operation. With the recent traumas we only found
      intraligamental ruptures or longitudinal fraying with ruptures of the femoral or
      tibial insertion. Postoperative plaster cast fixation for 6 weeks. Stability was
      examined by the "Arthrostress" (19 kp). In 11 cases no instability of clinical
      importance could be found, in 6 cases there was a +, in 3 cases a ++ and in 1
      case a 3-plus instability.

PMID- 1977291
TI  - [Work disability of injured patients].

PMID- 1977292
TI  - Control of expression and cell tropism of human immunodeficiency virus type 1.

PMID- 1977293
TI  - The "merry-go-round": alphaviruses between vertebrate and invertebrate cells.

PMID- 1977294
TI  - Management of overdose due to antihypertensive agents.

PMID- 1977295
TI  - Liver Imaging--Current Trends in MRI, CT, and US: international symposium and
      course, June 1990.

PMID- 1977296
TI  - Rheumatoid arthritis: current concepts and management, Part 2.
AB  - Rheumatoid arthritis is a systemic disorder, but primarily involves chronic
      polyarticular inflammation. Conservative nondrug therapy and NSAIDs are indicated
      initially and are effective treatment for many RA patients. For those individuals
      with progressive unresponsive disease an SAARD should be used. All SAARDs exhibit
      severe and frequent adverse effects with the risk-to-benefit ratio being the
      determining factor in deciding which agent to use. The first to be used is
      usually a gold compound; antimalarials and penicillamine provide alternatives to
      gold therapy. Sulfasalazine may gain a role in the therapy of early progressive
      RA. Methotrexate has recently been given FDA approval for use in RA and can be
      used, if the first three agents fail. Azathioprine and cyclophosphamide are
      cytotoxic agents with an increased risk of producing malignancies, but their use
      is sometimes required to halt serious progressive RA. Chlorambucil or cyclosporin
      A are relatively toxic agents that may play a role in treating refractory RA.
      Corticosteroids should be used for short-term adjunctive therapy as intra
      articular injections or oral therapy in individuals refractory to all other
      therapies. The use of SAARDs early in RA or in combination with one another is
      controversial.

PMID- 1977297
TI  - Role of beta-adrenergic blockers after percutaneous transluminal coronary
      angioplasty.
AB  - Restenosis after percutaneous transluminal coronary angioplasty (PTCA) cannot
      currently be prevented. Different medical regimens have been largely
      unsuccessful. Experimental studies suggest roles for beta-adrenergic blockers and
      calcium antagonists. Controlled clinical studies have failed to show any decrease
      in restenosis rate for calcium antagonists. Corresponding studies for beta
      blockers are lacking. This study evaluates 541 consecutive PTCA procedures, 455
      (86%) in patients treated with beta blockers after PTCA (76% metoprolol, 14%
      atenolol, 4% sotalol, 6% others) and 86 (14%) in patients without beta blockers.
      Angiographic success was achieved in 483 of 620 lesions (78%), and was not
      significantly different with or without beta blockers (79 vs 73%, p greater than
      0.05). The procedure success rate and the complication rates (myocardial
      infarction, emergency coronary artery bypass grafting, death) did not differ with
      or without beta blockers (p greater than 0.05). Follow-up angiograms for 426 of
      the 483 successfully dilated lesions (88%) revealed that a total of 155 stenoses
      had recurred (36%). The restenosis rate was not significantly different with
      (368) or without (58) beta blockers (36 vs 38%, p greater than 0.05). For beta
      blockers with calcium antagonists (84% nifedipine, 13% diltiazem, 2% verapamil,
      1% others), the restenosis rate was 97 of 250 (39%) vs 36 of 118 (31%) (p greater
      than 0.05). This retrospective study indicates that treatment with beta
      adrenergic blockers after PTCA, alone or in combination with calcium antagonists,
      does not influence either the success rate or the restenosis rate and can be
      continued if indicated from an antiischemic viewpoint.

PMID- 1977298
TI  - Introduction--Technetium-99m myocardial perfusion imaging agents and their
      relation to thallium-201.

PMID- 1977299
TI  - A symposium: Technetium-99m myocardial perfusion imaging agents and their
      relation to thallium-201. February 22-25, 1990, Palm Beach, Florida. Proceedings.

PMID- 1977300
TI  - Value of carvedilol in congestive heart failure secondary to coronary artery
      disease.
AB  - Despite considerable interest in the use of beta-blocking agents in congestive
      heart failure (CHF), their clinical application is limited because of their
      negative inotropic effects. Beta blockers with vasodilating properties may have
      the advantage of overcoming this, however. Carvedilol, a beta-blocking agent with
      vasodilating properties, was evaluated in 17 patients with chronic CHF secondary
      to ischemic heart disease with a resting left ventricular ejection fraction less
      than or equal to 45%, who were being maintained on diuretics. Exercise testing,
      radionuclide ventriculography, and right-sided cardiac catheterization were
      performed and intraarterial blood pressure measured before and after 8 weeks of
      carvedilol therapy in a dosage of 12.5 to 50.0 mg twice a day. Twelve patients
      completed the study and 5 withdrew. Symptomatic and hemodynamic improvement was
      demonstrated in 11 of the 12 patients. Heart rate and intraarterial blood
      pressure were both reduced by chronic therapy. Mean +/- standard deviation
      exercise time improved from 4.3 +/- 1.6 to 7.1 +/- 2.7 minutes (p less than
      0.0001), as did resting left ventricular ejection fraction, from 27 +/- 9 to 31
      +/- 11% (p less than 0.02). Pulmonary arterial wedge pressure fell from 19 +/- 7
      mm Hg to 12 +/- 5 mm Hg (p less than 0.001) and total systemic vascular
      resistance from 1,752 +/- 403 to 1,497 +/- 310 dynes/s/cm-5/m2 (p less than
      0.02). Stroke volume index improved also, from 31 +/- 6 ml to 40 +/- 6 ml (p less
      than 0.0005). These hemodynamic changes were mediated partly by vasodilation,
      diminished myocardial oxygen demand and reduction of sympathetic overactivity in
      the failing heart. These data suggest that carvedilol may have beneficial effects
      in patients with chronic CHF secondary to coronary artery disease.

PMID- 1977301
TI  - A symposium: primary and secondary prevention of cardiovascular disease. March
      22, 1990, New Orleans, Louisiana. Proceedings.

PMID- 1977302
TI  - Relevance of intrinsic sympathomimetic activity for beta blockers.
AB  - Intrinsic sympathomimetic activity (ISA) characterizes a group of beta blockers
      that are able to stimulate beta-adrenergic receptors (agonist effect) and to
      oppose the stimulating effects of catecholamines (antagonist effect) in a
      competitive way. Partial agonists are ligands that elicit a submaximal response
      when bound to beta receptors at maximal occupancy. In the isolated rat atrium,
      acebutolol produces a maximal stimulatory effect that is only 17 +/- 8% of the
      maximal effect induced by the full beta agonist isoproterenol. The presence of
      ISA results in less resting bradycardia and less of a reduction in cardiac output
      than is observed with beta blockers without ISA. In the long term, partial beta
      agonists may produce arterial vasodilation and increase arterial compliance,
      possibly leading to additional beneficial effects in the treatment of
      hypertension. beta blockers with ISA do not have adverse effects on plasma
      lipoproteins during long-term treatment; in addition, the presence of ISA could
      counteract the up-regulation of beta adrenoceptors often observed with beta
      blockers without ISA. Finally, the presence of ISA has been a conflicting issue
      for the use of such beta blockers in secondary prevention after myocardial
      infarction. However, the impressive results of the Acebutolol Prevention of
      Secondary Infarction trial in high-risk patients after myocardial infarction show
      that acebutolol, a beta blocker with moderate partial agonist activity, can be
      effective in decreasing the postinfarction mortality rate. By exhibiting a
      strikingly different hemodynamic profile from that of beta blockers without ISA,
      the partial beta agonists form an intriguing pharmacologic class of drugs for
      which prospective clinical trials should be extensively pursued.

PMID- 1977304
TI  - Proceedings from the international conference: geriatric nephrology and urology:
      interdisciplinary perspectives. Toronto, Ontario, Canada, April 14-16, 1989.

PMID- 1977303
TI  - Secondary prevention of acute myocardial infarction with beta-blocking agents and
      calcium antagonists.
AB  - The discovery that beta blockers possess clinically useful hypotensive,
      antianginal and antiarrhythmic properties has attracted the interest of
      clinicians, researchers and the pharmaceutical community alike. In addition,
      minor differences in a variety of ancillary properties have led to speculation
      that specific classes of drugs might have advantages over other classes. The
      enthusiasm that greeted reports from the first small trials, which showed that
      beta blockers reduced the postmyocardial infarction mortality rate, attracted the
      commercial support necessary to evaluate different beta blockers in this clinical
      setting. The plethora of beta blockers that subsequently became available for
      study led to considerable improvement in both the design and implementation of
      large clinical trials. Despite apparent discrepancies in the results of various
      trials, meta-analysis indicates that most, if not all, beta blockers reduce
      postinfarction mortality. However, because meta-analysis cannot recommend a
      particular drug or specific dose for use in an individual patient, clinical
      practice must be based on the results of individual trials, not on the
      conclusions of meta-analysis. The clinical utility of beta blockers in the
      secondary prevention of myocardial infarction, coupled with experimental evidence
      that calcium antagonists reduce infarct size, led to a series of large studies
      designed to establish whether calcium antagonists have any effect on reducing
      mortality in patients with myocardial infarction. Lessons learned from the beta
      blocker trials permitted a more rapid evaluation of the efficacy of calcium
      antagonists in this setting. It is clear that, unlike beta blockers, calcium
      antagonists are not effective in the secondary prevention of myocardial
      infarction.

PMID- 1977305
TI  - Cardiac contractility and conduction: a comparison of antihypertensives.
AB  - The four classes of first-line antihypertensive agents recommended in the 1988
      report of the Joint National Committee on Detection, Evaluation, and Treatment of
      High Blood Pressure are reviewed here. Particular consideration is given to the
      effects of these agents on heart rate, atrioventricular nodal conduction, and
      myocardial contractility in patients with other cardiovascular diseases.
      Diuretics and angiotensin-converting enzyme inhibitors have no significant direct
      effects on cardiac function. beta-Blockers inhibit catecholamine stimulation of
      the heart and may be particularly beneficial in treating patients with a history
      of myocardial infarction. Calcium channel blockers reduce blood pressure by
      dilating arterial resistance vessels. They are structurally heterogeneous and
      highly selective in their sites of action. As a consequence, cardiac effects can
      be minimized by selecting a calcium channel blocker with more potent peripheral
      vasodilatory effects. A new calcium channel blocker, isradipine, currently
      undergoing clinical trials, is highly selective for arterial smooth muscle and
      appears to be a safe and effective antihypertensive agent.

PMID- 1977306
TI  - Benign missense variations in the cystic fibrosis gene.
AB  - The common mutation causing cystic fibrosis is a deletion of phenylalanine 508
      (delta F508), which occurs in a putative nucleotide-binding fold of the gene
      product. We report two additional mutations, substitution of cysteine for
      phenylalanine 508 (F508C) and substitution of valine for isoleucine 506 (I506V).
      Three compound heterozygous persons, two delta F508/F508C and one delta
      F508/I506V, had normal clinical and epithelial physiological studies indicating
      that the F508C and I506V mutations are benign. This opportunity to study the in
      vivo function of these mutations suggests that amino acid substitutions are more
      benign than changes in the length of this portion of the putative nucleotide
      binding fold. These mutations must be taken into account when performing
      molecular diagnosis and carrier detection for cystic fibrosis.

PMID- 1977307
TI  - Linkage relationship of X-linked juvenile retinoschisis with Xp22.1-p22.3 probes.
AB  - Linkage analysis was performed to evaluate the relationship between the locus for
      X-linked juvenile retinoschisis (RS) and five X-chromosomal markers-RC8 (DXS9),
      SE3.2L (DXS16), 99-6 (DXS41), D2 (DXS43), and 782 (DXS85)-all mapped to the
      interval Xp22.1-p22.3. Seven U.S. families with 56 affected males were studied.
      No recombinants were found between RS and DXS9 with a maximum lod score (Z) of
      4.93 at a recombination fraction of zero. Obligate recombinants were found for RS
      with DXS16, DXS41, DXS43, and DXS85. Multipoint linkage analysis and
      consideration of recombination events within pedigrees suggest that DXS41 and
      DXS43, and also DXS41 and DXS16, flank RS and that DXS85 lies outside the
      interval DXS41-DXS43. Our pedigrees provide no evidence for genetic heterogeneity
      of RS, with five of our families individually showing evidence of linkage. (Z
      greater than 2.0) to the least one of these probes from Xp22.1-p22.3.

PMID- 1977308
TI  - Genetics and biology of human ovarian teratomas. II. Molecular analysis of origin
      of nondisjunction and gene-centromere mapping of chromosome I markers.
AB  - Chromosomal heteromorphisms and DNA polymorphisms have been utilized to identify
      the mechanisms that lead to formation of human ovarian teratomas and to construct
      a gene-centromere map of chromosome 1 by using those teratomas that arise by
      meiotic nondisjunction. Of 61 genetically informative ovarian teratomas, 21.3%
      arose by nondisjunction at meiosis I, and 39.3% arose by meiosis II
      nondisjunction. Eight polymorphic marker loci on chromosome 1p and one marker on
      1q were used to estimate a gene-centromere map. The results show clear linkage of
      the most proximal 1p marker (NRAS) and the most proximal 1q marker (D1S61) to the
      centromere at a distance of 14 cM and 20 cM, respectively. Estimated gene
      centromere distances suggest that, while recombination occurs normally in ovarian
      teratomas arising by meiosis II errors, ovarian teratomas arising by meiosis I
      nondisjunction have altered patterns of recombination. Furthermore, the estimated
      map demonstrates clear evidence of chiasma interference. Our results suggest that
      ovarian teratomas can provide a rapid method for mapping genes relative to the
      centromere.

PMID- 1977309
TI  - Definitive localization of X-linked Kallman syndrome (hypogonadotropic
      hypogonadism and anosmia) to Xp22.3: close linkage to the hypervariable repeat
      sequence CRI-S232.
AB  - Kallmann syndrome is a genetically heterogeneous disease characterized by
      hypogonadotropic hypogonadism and anosmia. Six families in which the disorder
      followed an X-linked inheritance were investigated by linkage analysis.
      Diagnostic criteria were uniformly applied and included tests for
      hypogonadotropic hypogonadism and anosmia. Close linkage was found by using the
      hypervariable repeated sequence CRI-S232 (DXS278) previously mapped to Xp22.3. At
      a maximum lod score of 6.5, the recombination fraction was calculated as .03. Of
      30 fully informative meioses, one recombination between the disease locus and the
      loci recognized by probe CRI-S232 was observed. When an independent approach is
      used, these results confirm the X-linked Kallmann syndrome assignment previously
      made by deletion mapping, and allow definitive localization of the syndrome
      assignment previously made by deletion mapping, and allow definitive localization
      of the syndrome to the Xp22.3 region. This opens the way to carrier detection and
      to the identification of a gene responsible for this disorder.

PMID- 1977310
TI  - Haplotype analysis of the human apolipoprotein B mutation associated with
      familial defective apolipoprotein B100.
AB  - Haplotype analysis was conducted on the mutant allele of 14 unrelated subjects
      heterozygous for a mutation in the codon for amino acid 3500 of human
      apolipoprotein B100. This mutation is associated with defective binding of low
      density lipoprotein to the low-density lipoprotein receptor and with moderate
      hypercholesterolemia. Ten markers were used for haplotyping: eight diallelic
      markers within the structural gene and two hypervariable loci flanking the gene.
      Seven of eight unequivocally deduced haplotypes were identical, and one revealed
      only a minor difference at one of the hypervariable loci. The genotypes of the
      six other affected subjects were consistent with this same assigned haplotype.
      These data are consistent with a common ancestral chromosome and provide no
      evidence for a recurrent mutation at this potentially hypermutable CG
      dinucleotide, despite the fact that this mutation is not rare.

PMID- 1977311
TI  - Heterozygous mutations at the mut locus in fibroblasts with mut0 methylmalonic
      acidemia identified by polymerase-chain-reaction cDNA cloning.
AB  - Genetic defects in the enzyme methylmalonyl CoA mutase cause a disorder of
      organic acid metabolism termed "mut methylmalonic acidemia." Various phenotypes
      of mut methylmalonic acidemia are distinguished by the presence (mut-) or absence
      (mut0) of residual enzyme activity. The recent cloning and sequencing of a cDNA
      for human methylmalonyl CoA mutase enables molecular characterization of
      mutations underlying mut phenotypes. We identified compound heterozygous
      mutations in a mut0 fibroblast cell (MAS) line by cloning the methylmalonyl CoA
      mutase cDNA by using the polymerase chain reaction (PCR), sequencing with
      internal primers, and confirming the pathogenicity of observed mutations by DNA
      mediated gene transfer. Both mutations alter amino acids common to the normal
      human, mouse, and Propionibacterium shermanii enzymes. This analysis points to
      evolutionarily preserved determinants critical for enzyme structure or function.
      The application and limitation of cDNA cloning by PCR for the identification of
      mutations are discussed.

PMID- 1977313
TI  - Parental origin of chromosome 22 alleles lost in meningioma.

PMID- 1977314
TI  - Agricultural, occupational and environmental health: policy strategies for the
      future--the scientific basis. Part II. A conference. Iowa City, Iowa and Des
      Moines, Iowa, September 17-30, 1988. Proceedings.

PMID- 1977312
TI  - A human D1 dopamine receptor gene is located on chromosome 5 at q35.1 and
      identifies an EcoRI RFLP.
AB  - Dopaminergic neurons have been shown to affect voluntary movement, hormone
      secretion, and emotional tone. Mediating these activities are two receptor
      subtypes, D1 and D2, which are biochemically and pharmacologically distinct. The
      D1 subtype, the most abundant form of dopamine receptor in the central nervous
      system, stimulates adenylate cyclase, modulates D2 receptor activity, regulates
      neuron growth and differentiation, and mediates several behavioral responses.
      Recently we reported the cloning of a human D1 dopamine receptor gene (DRD1).
      High-stringency hybridization of the DRD1 clone to human genomic blots suggests
      that DRD1 is single copy. When used to probe a Southern blot made with DNAs from
      a rodent-human somatic cell hybrid panel, DRD1 hybridized to a 6.5-kb EcoRI
      restriction fragment which was assigned to chromosome 5. Fluorescent in situ
      hybridization of this gene to human metaphase chromosomes refined the location of
      DRD1 to 5q35.1. A search for RFLPs associated with DRD1 identified a two-allele
      EcoRI RFLP, allowing confirmation of DRD1's localization by linkage analysis in
      Centre d'Etude du Polymorphisme Humain families.

PMID- 1977315
TI  - Technical workshop report: Working Group I: Occupational health and safety
      strategies for agriculture.
AB  - The six workshops in this subgroup--Injuries, Respiratory Diseases, Acute
      Chemical Toxicity, Cancer, and Health Surveillance--competently outlined the
      principal health and safety issues in agriculture, documenting the increased and
      unacceptable morbidity and mortality in farmers and their families. It became
      evident that although research knowledge is just now unfolding, sufficient data
      exist to permit comprehensive program planning for research and prevention. It is
      necessary that farmers and their families be considered an occupational grouping
      and that specific programs aimed at ongoing risk assessment and early diagnosis
      are important. At the same time, a more broadly based approach to rural family
      life enhancement is essential, including the following: 1) education; 2)
      prevention; 3) family life enhancement; and 4) research. Because of the scope and
      nature of the problem, program development should include a multidisciplinary
      approach that involves the local community, state government, university
      (professional) resources, farm/organizations, and industry.

PMID- 1977316
TI  - Decision analysis applied to selection of histamine H2-receptor antagonists for
      the formulary.
AB  - The use of decision analysis in selecting a histamine H2-receptor antagonist for
      the formulary at a hospital in Spain is described. Cimetidine, ranitidine, and
      famotidine were identified as the possible alternatives. The evaluation criteria
      established were therapeutic efficacy, adverse effects, drug interactions, years
      of clinical use, dosage interval, cost, and dosage forms. The relative importance
      of the criteria was determined by assigning utility values to each. Probability
      values were assigned to estimate how well each drug met each criterion. By
      multiplying the utility and probability values for each criterion and summing the
      scores, a total score was calculated for each drug. The alternative with the
      highest total score was ranitidine. A sensitivity analysis showed that the
      results were stable over a plausible range of probability and utility values.
      Accordingly, ranitidine was selected for inclusion on the formulary. Decision
      analysis provided an effective method for selecting which histamine H2-receptor
      antagonist to include on the hospital's formulary.

PMID- 1977317
TI  - Drug-use review program for concurrent histamine H2-receptor antagonist
      sucralfate therapy.
AB  - The effect of drug-use review on concomitant histamine H2-receptor antagonist
      sucralfate therapy at a 600-bed, university-affiliated Veterans Affairs medical
      center was studied. In an effort to curtail the concomitant use of H2-antagonist
      plus sucralfate therapy, the department of pharmacy, in conjunction with the
      gastroenterology service, developed and introduced criteria for the appropriate
      use of combination therapy. The extent of prescribing of concomitant histamine H2
      receptor antagonist-sucralfate therapy before and after implementation of
      criteria-based guidelines and the appropriateness of current H2-receptor
      antagonist-sucralfate combination therapy, based on the guidelines, were
      assessed. The effectiveness of the intervention process was evaluated, and cost
      savings associated with intervention were calculated. After intervention, the
      number of treatment courses of histamine H2-receptor antagonist-sucralfate
      combination therapy decreased by 30%. However, of the 109 evaluable
      postintervention combination treatment courses, only one complied with both the
      indication and the duration of treatment criteria. This review of prescribing
      patterns and the implementation of criteria-based guidelines proved an effective
      means of reducing inappropriate combination therapy and resulted in annual cost
      savings of $25,000.

PMID- 1977318
TI  - Toward a new standard in oral contraception. Proceedings of a symposium held at
      the XIII World Congress on Fertility and Sterility. Marrakesh, Morocco, October
      3, 1989.

PMID- 1977319
TI  - An immunohistochemical study of pi class glutathione S-transferase expression in
      normal human tissue.
AB  - Glutathione S-transferases (GSTs), a family of isoenzymes that play an important
      role in protecting cells from cytotoxic and carcinogenic agents, can be separated
      by biochemical and immunologic characteristics into three distinct classes named
      alpha, mu, and pi. Previous studies have indicated that there is marked
      heterogeneity in the expression of different GST isoenzymes in different normal
      and malignant tissues. To better understand the regulation of the human pi class
      glutathione S-transferase isoenzyme (GST-pi), the tissue distribution of this
      protein wa studied by an immunohistochemical technique using an anti-GST-pi
      polyclonal antibody in normal paraffin-embedded human tissues. These studies
      indicate that there is a broad distribution of GST-pi in normal human tissues and
      establish a precise localization within the different organs studied. GST-pi was
      expressed predominantly in normal epithelial cells of the urinary, digestive, and
      respiratory tracts, suggesting a possible role for GST-pi in detoxication and
      elimination of toxic substances. Previous studies have indicated that GST-pi and
      the putative drug efflux pump P-glycoprotein are both overexpressed in multidrug
      resistant human breast cancer cells and in xenobiotic resistant preneoplastic rat
      hyperplastic liver nodules. Results from this study indicate that there are also
      similarities between the normal tissue distribution GST-pi and that previously
      reported for mammalian P-glycoprotein, particularly in secretory epithelia. This
      finding suggests that these two gene products, which have been implicated in the
      development of resistance to cytotoxic drugs, may be coregulated in normal and
      malignant cells.

PMID- 1977320
TI  - Binding of monoclonal antibodies to glomerular endothelium, slit membranes, and
      epithelium after in vivo injection. Localization of antigens and bound IgGs by
      immunoelectron microscopy.
AB  - The antigens recognized by seven monoclonal antibodies (MAbs) raised against rat
      glomerular proteins were localized, and the sites of binding of the MAbs after in
      vivo injection were determined by immunoelectron microscopy. The antigens were
      localized in situ by immunoperoxidase and immunogold labeling to different
      domains and microdomains of the glomerular endothelium and epithelium. 23A
      recognized an antigen expressed exclusively on the luminal (apical) domain of the
      endothelium. 5A (anti-podocalyxin) and 26C (anti-DPPIV) recognized antigens
      expressed on the apical domains of both the endothelium and podocytes. 13A, 14A,
      20B (anti-gp330), and 27A recognized antigens restricted to podocytes in the
      glomerulus. The 13A antigen was present on their basal surface and the 27A and
      14A antigens were expressed on both their apical and basal domains. The 14A
      antigen also was associated with the filtration slit membranes. All these MAbS
      bound to their antigens after injection in vivo. Those that recognize endothelial
      antigens were rapidly cleared from the circulation and rapidly disappeared from
      glomeruli, whereas those that recognize epithelial antigens persisted in the
      circulation and were detectable in glomeruli for hours or days. The sites of
      binding of the MAbs differed: 23A and 5A IgG (antipodocalyxin) bound exclusively
      to the luminal domain of the endothelium, whereas 26C IgG (anti-DPPIV) bound to
      both the luminal endothelial membrane and the apical and basal domains of
      podocytes. The MAbs that recognize podocyte antigens bound to different domains
      of the podocyte plasmalemma: 13A and 27A IgGs to the basal domain, 14A to the
      slit membranes, and 20B to coated pits on the entire plasma membrane. 27A IgG led
      to the formation of small subepithelial immune deposits that remained up to 10
      days. It is concluded that 1) glomerular membrane proteins vary considerably in
      their distribution among plasmalemmal domains and microdomains of endothelial and
      epithelial cells; 2) virtually all structures in the glomerulus and all domains
      and micro-domains of the endothelium and podocyte are accessible to circulating
      antibodies; and 3) the fate of immune complexes formed by binding to glomerular
      components varies with the location of the antigen within the glomerulus, with
      those that bind to the basal domain and slit membranes of the podocyte persisting
      longer than the others.

PMID- 1977321
TI  - Effect of hypoinsulinemia and hyperglycemia on fetal glucose utilization.
AB  - The present studies were performed to determine the effect of normal levels of
      insulin on fetal glucose metabolism and to measure the acute changes in insulin
      secretion and concentration that occur in response to a hyperglycemia stimulus.
      In fetal sheep, infusion of somatostatin alone decreased fetal insulin
      concentration 4 microU/ml (33%) from the basal value without a significant change
      in fetal glucose concentration, umbilical glucose uptake (UGU), or fetal glucose
      utilization rate (GUR). Glucose plus somatostatin infusion produced a
      significantly lower insulin concentration (54% lower, P less than 0.005) and GUR
      (22% lower, P less than 0.05) at glucose concentration approximately 40 mg/dl
      compared with glucose infusion alone. No significant difference was seen at
      glucose concentration of approximately 30 mg/dl. These results indicate that
      fetal glucose metabolism is responsive not only to changes in glucose but also
      insulin concentrations; however, a relatively large change in insulin (greater
      than 5 microU/ml) is necessary to produce a measurable response. These
      quantitative aspects of fetal insulin effect must be considered when assessing
      the role of insulin in the regulation of fetal glucose metabolism.

PMID- 1977322
TI  - Lack of effect of hyperglycemia on lipolysis in humans.
AB  - Controversy exists regarding whether plasma glucose concentrations are
      independently involved in the regulation of adipose tissue lipolysis. In the
      present study, six subjects with insulin-dependent diabetes and six nondiabetic
      volunteers were studied during infusion of somatostatin, growth hormone, and
      insulin at rates designed to maintain basal rates of lipolysis, which was traced
      using a constant infusion of [1-14C]palmitate. A euglycemic (approximately 5
      mmol/l) clamp was performed for 3 h, followed by 3 h of hyperglycemia
      (approximately 9 and approximately 11 mmol/l in nondiabetic and diabetic
      subjects, respectively). Ten nondiabetic subjects were studied during 6 h of
      euglycemia to exclude time-dependent changes in lipolysis. The results showed
      that palmitate concentrations did not change between euglycemia and hyperglycemia
      in either group [118 +/- 10 vs. 132 +/- 14 mumol/l and 145 +/- 21 vs. 134 +/- 15
      mumol/l in nondiabetic and diabetic subjects, respectively; both P = not
      significant (NS)]. Similarly, palmitate rate of appearance (Ra) did not change
      during hyperglycemia (1.0 +/- 0.1 and 1.7 +/- 0.4 mumol.kg-1.min-1 in nondiabetic
      and diabetic subjects, respectively) compared with euglycemia (1.0 +/- 0.1 and
      1.6 +/- 0.4 mumol.kg-1.min-1 in nondiabetic and diabetic subjects, respectively;
      P = NS). Palmitate concentrations and Ra did not change during 6 h of euglycemia
      in nondiabetic volunteers. Thus hyperglycemia per se has no effect on free fatty
      acid turnover. Changes in lipolysis that occur coincident with hyperglycemia are
      probably due to changes in other circulating substrates or hormones known to
      affect lipolysis.

PMID- 1977323
TI  - Antibody against leukocyte integrin (CD18) prevents reperfusion-induced lung
      vascular injury.
AB  - We studied the effects of pretreatment of rabbits with a monoclonal antibody
      (MoAb) IB4 directed against an epitope on the common beta-chain of leukocyte
      adhesion glycoprotein CD18 on the development of pulmonary edema following
      pulmonary artery occlusion and reperfusion. A balloon catheter occluded the right
      pulmonary artery in rabbits for 24 h, and the balloon was then deflated to allow
      reperfusion for 2 h. The lungs were removed, attached to a weighing balance, and
      perfused with Ringer-albumin solution (0.5 g/100 ml). IB4 (0.5 mg/kg) was infused
      45 min before the start of reperfusion. In another experiment, we infused OKM-1
      (0.5 mg/kg), a control MoAb directed against an irrelevant epitope on the alpha
      chain of CD11b/CD18. IB4 prevented rabbit neutrophil adherence to pulmonary
      artery endothelial cells in vitro in response to a variety of stimuli, whereas
      OKM-1 was ineffective. Pulmonary artery occlusion and reperfusion increased the
      lung myeloperoxidase (MPO) content, whereas IB4 prevented the increase in MPO
      content. The increase in lung weight in the IB4-treated group (400 +/- 40 mg from
      baseline) was less (P less than 0.001) than in the untreated control group (1,400
      +/- 90 mg) and the OKM-1-treated control group (1,320 +/- 125 mg). IB4
      pretreatment also prevented the increase in pulmonary capillary filtration
      coefficient (a measure of capillary permeability to water) occurring in control
      and OKM-1-treated groups. The results indicate that neutrophil sequestration in
      the pulmonary microcirculation mediated by CD18 glycoprotein is a major
      determinant of reperfusion-induced lung vascular injury.

PMID- 1977324
TI  - Reduced beta-agonist sensitivity in single atrial cells from failing human
      hearts.
AB  - Human myocytes were isolated from right atrial appendage, and contractile
      responses to inotropic agents were studied. Responses to inotropic agents of
      cells isolated from patients with mild heart disease [New York Heart Association
      (NYHA) classes I and II] were compared with those of myocytes from rabbit atria.
      Maximally effective concentrations of calcium, forskolin, and isoproterenol
      increased contraction amplitude to a similar extent (11.9, 11.5, and 11.3% change
      in cell length, respectively), but histamine produced a smaller effect (7.1%).
      The maximum responses of rabbit atrial cells to calcium (18.5%) and isoproterenol
      (15.0%) were significantly greater than human. In human cells, the velocity of
      contraction or relaxation was accelerated more by isoproterenol (P less than
      0.05) or forskolin (P less than 0.01) than by high calcium. Only relaxation
      velocity was increased by isoproterenol in rabbit cells (P less than 0.05).
      Rabbit myocytes contracted and relaxed 10-30% faster than human (P less than
      0.05). Cells from the atria of patients with New York Heart Association (NYHA)
      heart failure class III or IV were less responsive to isoproterenol than those
      from class I or II (P less than 0.01). Omitting data from patients who had been
      taking calcium-channel blockers or beta-adrenoceptor agonist or antagonist drugs
      did not affect the conclusions. Analysis of variance revealed a significantly
      greater between-patient than within-patient variation (P less than 0.001),
      indicating that cells from the same patient have a tendency to respond in a
      similar way. Responses to high calcium did not differ among NYHA classes. The
      effect of forskolin was not reduced in NYHA class III, although there was a
      decreased response in cells from two patients in NYHA class IV.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1977325
TI  - Cardiovascular responses to vasoactive intestinal contractor, a novel endothelin
      like peptide.
AB  - Cardiovascular and pulmonary responses to vasoactive intestinal contractor (VIC),
      an endothelin (ET)-like peptide from the murine gastrointestinal tract, were
      investigated in the cat. VIC (0.1-1.0 nmol/kg iv) decreased or elicited biphasic
      changes in arterial pressure (AP) and increased central venous pressure, cardiac
      output, pulmonary arterial pressure, and left atrial pressure. VIC produced
      biphasic changes in systemic vascular resistance (SVR) and pulmonary vascular
      resistance (PVR). VIC increased heart rate (HR) and, at the 1 nmol/kg dose, a
      secondary decrease was observed. Hexamethonium blocked the changes in HR in
      response to VIC, whereas the ganglionic blocker, meclofenamate, or glybenclamide
      had no effect on changes in AP, SVR, and PVR elicited by the peptide. VIC caused
      small changes in right ventricular contractile force and increased distal aortic
      and carotid artery blood flow at all doses, with secondary decreases at the
      higher doses. VIC decreased superior mesenteric artery flow and decreased renal
      blood flow at the 1 nmol/kg dose. The changes in AP in response to VIC, ET-1, and
      ET-2 were similar, whereas those elicited by ET-3 and sarafotoxin 6b were
      similar. The present data show that VIC can produce both vasodilation and
      vasoconstriction in the systemic vascular bed and biphasic changes in PVR in the
      cat. These data show that VIC can produce complex cardiovascular responses
      similar to those elicited by the ET peptides and that these responses are largely
      independent of autonomic reflexes, release of cyclooxygenase products, and
      activation of ATP-regulated potassium channels. We conclude that VIC may act as
      an ET-like peptide.

PMID- 1977326
TI  - Non-NMDA receptors mediate sensory afferent synaptic transmission in medial
      nucleus tractus solitarius.
AB  - Indirect evidence suggests that excitatory amino acids (EAA) are involved in
      synaptic transmission of visceral afferents at their synapses within the nucleus
      tractus solitarius (NTS). Little is known about the identity of the postsynaptic
      receptors or response mechanisms. Here we report results from a longitudinal
      brain slice of the rat medulla. Intracellular recordings were made from neurons
      in delimited portions of the dorsal medial NTS (mNTS) known to receive
      baroreceptor inputs. Stimulation of the solitary tract 1-3 mm from the mNTS
      recording site evoked short (2 ms) latency excitatory postsynaptic potentials
      (EPSPs), which had durations of 40-50 ms. Addition of the non-N-methyl-D
      aspartate (non-NMDA) selective antagonist 6-cyano-7-nitro-quinoxaline-2,3-dione
      (CNQX) to the slice surface near the recording electrode resulted in a rapid
      (within 30-45 s) suppression of the EPSP. Complete EPSP blockade was only slowly
      reversed by drug-free saline. Concentration-response relations (n = 14) showed
      50% depression of EPSPs by surface concentrations of 1-10 microM CNQX. EPSP
      amplitude was resistant to the selective NMDA antagonist 2-amino-5
      phosphonovalerate (AP 5) and, on average, was reduced less than 20% at 100 microM
      AP 5, an effect that was not statistically significant (n = 10; P greater than
      0.05). In conclusion, this study offers the first direct evidence that EAAs
      mediate the primary events of afferent synaptic transmission in NTS. The
      experiments suggest that excitatory sensory afferent synaptic transmission to
      mNTS neurons is mediated by an EAA transmitter acting at non-NMDA receptors, but
      NMDA receptors may have a modulatory role.

PMID- 1977327
TI  - Effects of stress and exercise on rat hippocampus and striatum extracellular
      lactate.
AB  - Extracellular lactate was continuously monitored (lactography) to determine the
      effect of various stressors to assess glucose metabolism in the rat hippocampus
      and striatum. It appeared that immobilization, emotional stress, and exercise
      (physiological stress) all resulted in an increase in hippocampal extracellular
      lactate. Exercise had the most pronounced effect. These increases were different
      for rats raised in different laboratories. Only during exercise a transient
      increase in lactate was seen in striatum. Peripheral infusions of epinephrine
      and/or corticosterone did not affect the basal levels of hippocampal lactate.
      Adrenodemedullated rats showed an attenuated lactate increase compared with
      control rats during and shortly after exercise. Administration of ipsapirone, an
      anxiolytic drug, attenuated the stress-induced formation of the hippocampal
      lactate. The present study demonstrates the usefulness of lactography to monitor
      regional brain metabolism in freely moving animals, exposed to various stressors,
      breeding conditions, or drugs. The observed different responsiveness of the two
      brain-region studies emphasizes the different involvement of the striatum and
      hippocampus in motor and emotional behavior, respectively. Lactate formation is
      stimulated by excitatory neuronal activity, presumably originating in the
      cerebral cortex, although adrenal hormones appear to contribute.

PMID- 1977328
TI  - A discriminant validity study of negative symptoms with a special focus on
      depression and antipsychotic medication.
AB  - If the construct validity of the negative symptom syndrome is to be established,
      the conceptual and operational overlap between negative symptoms and other
      syndromes such as depression and the effects of medication must be explained. The
      author assessed 26 patients with schizophrenia and 21 patients without
      schizophrenia, most of whom had depression, at the end of an average 2-week drug
      washout period and after approximately 2 months of psychotropic medication
      administration. Negative symptoms were remarkably consistent in patients with
      schizophrenia despite pharmacological intervention. In contrast, the patients
      without schizophrenia manifested significant decreases in negative symptoms.

PMID- 1977329
TI  - Effects of sedatives and neuroleptics.

PMID- 1977330
TI  - Intraocular pressure during rapid sequence induction: use of moderate-dose
      sufentanil or fentanyl and vecuronium or atracurium.
AB  - We studied the effect of rapid sequence induction of anaesthesia on intraocular
      pressure in physically fit, ASA class I or II patients using combinations of
      sufentanil (1 microgram/kg), or fentanyl (5 micrograms/kg) and vecuronium (0.2
      mg/kg) or atracurium (1.0 mg/kg). All patients received thiopentone (5 mg/kg),
      following which those in group 1 received sufentanil and vecuronium, group 2
      sufentanil and atracurium, group 3 fentanyl and vecuronium, and group 4 fentanyl
      and atracurium. Laryngoscopy and intubation were performed 60 seconds after
      induction. Intraocular pressure was measured prior to induction, 30 and 60
      seconds after induction, immediately after intubation, and postintubation for 5
      minutes. Postinduction and postintubation intraocular pressure values in all four
      groups did not exceed baseline values. We conclude that in fit patients, the
      combination of thiopentone, moderate dose narcotics, and an appropriate dose of
      vecuronium or atracurium produces satisfactory conditions for intubation
      following rapid sequence induction without increases in intraocular pressure.
      This technique should not, however, be employed when multiple other injuries are
      present, along with an open eye.

PMID- 1977331
TI  - Isoflurane-induced vasodilation: role of the alpha-adrenergic nervous system.
AB  - Isoflurane is a potent systemic vasodilator. Because isoflurane vasodilation is
      clinically significant, we sought to explore whether decreases in systemic
      vascular resistance caused by isoflurane involve the alpha-adrenergic nervous
      system in humans. Specifically, we tested the hypothesis that isoflurane systemic
      vasodilation is mediated via inhibition of vascular alpha 1-adrenergic
      responsiveness. Phenylephrine pressor dose-response curves were established
      before anesthesia and during isoflurane/oxygen anesthesia in patients undergoing
      coronary artery bypass surgery; all patients included in the study (n = 11)
      demonstrated significant (P = 0.0001) decreases in systemic vascular resistance
      when isoflurane was given in concentrations adequate to produce a 20% decrease in
      mean arterial blood pressure. Polynomial regression of the phenylephrine dose
      response curve was used to estimate the phenylephrine dose required to increase
      mean arterial blood pressure 15 mm Hg, designated PD15 mm Hg. Each patient served
      as his or her own control. Preanesthetic baseline PD15 mm Hg values (115 +/- 23
      micrograms [1.4 +/- 0.3 micrograms/kg], mean +/- SEM) were not significantly
      different from isoflurane PD15 mm Hg values (124 +/- 20 micrograms [1.5 +/- 0.3
      micrograms/kg]). End-tidal isoflurane concentration ranged from 0.6%-1.5%;
      isoflurane PD15 mm Hg was not correlated with end-tidal isoflurane concentration.
      Patient characteristics and hemodynamics did not affect PD15 mm Hg. These results
      suggest that isoflurane-induced systemic vasodilation is not mediated via
      inhibition of alpha 1-adrenergic responsiveness, disproving our hypothesis. This
      finding has clinical importance because it demonstrates that alpha 1-adrenergic
      stimulation with phenylephrine is effective in correcting hypotension in patients
      receiving isoflurane anesthesia.

PMID- 1977332
TI  - Does sufentanil produce less ventilatory depression than fentanyl?

PMID- 1977333
TI  - Preventing unauthorized access to narcotics in the operating room.

PMID- 1977334
TI  - Neuromuscular effects of respiratory and metabolic acid-base changes in vitro
      with and without nondepolarizing muscle relaxants.
AB  - The effects of metabolic (bicarbonate, [HCO3]) and respiratory (carbon dioxide,
      PCO2) acid-base changes on indirectly elicited twitch tension with and without
      nondepolarizing neuromuscular blocking agents were compared in a rat phrenic
      nerve-hemidiaphragm preparation. Ionized calcium [Ca2+] and magnesium [Mg2+]
      concentrations in the modified Krebs' solution were measured and kept constant.
      Likewise, twitch was altered when pH changes were produced by altering either
      PCO2 or [HCO3]. Decreasing pH either by increasing PCO2 or by decreasing [HCO3]
      significantly decreased (P less than 0.01) twitch, by 9.5 +/- 0.6 (SEM, n = 8)
      and 10.6 +/- 1.5%, respectively. Increasing pH by decreasing PCO2 or by
      increasing [HCO3] significantly increased (P less than 0.01) twitch, by 5.6 +/-
      0.9 and 7.9 +/- 0.6%, respectively. After a partial depression of twitch by
      nondepolarizing neuromuscular blocking agents, the effects of PCO2 and [HCO3]
      changes were again assessed. Decreasing pH by increasing PCO2 or by decreasing
      [HCO3] intensified d-tubocurarine (dTc) (28.2 +/- 1.6 and 32.0 +/- 2.9%,
      respectively) and vecuronium (23.0 +/- 1.4 and 36.8 +/- 3.2%, respectively)
      block, whereas it reversed metocurine (1.2 +/- 2.2% NS and 2.9 +/- 1.3%,
      respectively) and pancuronium (8.3 +/- 1.5 and 11.5 +/- 3.0%, respectively)
      block. Conversely, increasing pH by decreasing PCO2 or by increasing [HCO3]
      antagonised dTc (12.8 +/- 2.2 and 13.6 +/- 1.8%, respectively) and vecuronium
      (25.3 +/- 1.7 and 25.0 +/- 3.0%, respectively) block, whereas it potentiated
      metocurine (4.2 +/- 0.6 and 8.0 +/- 1.1%, respectively) and pancuronium (11.0 +/-
      1.2 and 17.5 +/- 2.0%, respectively) block. Except where indicated, all changes
      in block described above were statistically significant.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1977335
TI  - Hemodynamic effects of nebivolol at rest and on exertion in patients with heart
      failure.
AB  - Nebivolol is a novel B-1-adrenoceptor-blocking drug with an unusual hemodynamic
      profile unlike classical B-blockers. In dogs and in healthy volunteers it
      decreases blood pressure and heart rate but improves left ventricular function.
      The authors studied 10 male patients with coronary artery disease and heart
      failure (ejection fraction mean = 46%). A Swan-Ganz catheter was placed into the
      pulmonary artery, and the mean blood pressure, the heart rate, the pulmonary
      artery pressure, the pulmonary wedge pressure, the right atrial pressure, the
      cardiac output, and the stroke volume were measured at rest and on exertion
      before and after seven days' treatment with oral nebivolol (5 mg/day). While the
      blood pressure and the heart rate decreased significantly, the pulmonary artery
      and wedge pressures, as well as the right atrial pressure and the cardiac output,
      did not change during treatment. The stroke volume increased significantly. The
      maintained cardiac output cannot be explained by any changes in preload or
      afterload; instead a positive inotropic mechanism must be assumed. Unlike other B
      blockers it seems to be possible to treat patients with heart failure with
      nebivolol without causing the hemodynamic situation to deteriorate.

PMID- 1977336
TI  - Chronic arterial occlusion with PGE1-resistant skin lesions treated by
      glycosaminoglycan compound--case reports.
AB  - The authors report on 2 patients with chronic arterial occlusion in whom the
      intravenous administration of the glycosaminoglycan compound FPFD 101 was
      markedly effective. One patient suffered from thromboembolic episodes of the left
      hand, and the other had peripheral circulatory impairment related to collagen
      disease. In these patients, the oral administration of anticoagulants and
      antiplatelet agents in combination with intravenous infusion of prostaglandin E1
      was not adequately effective. However, the addition of intravenous injection of
      FPFD 101 resulted in a marked improvement in their symptoms. FPFD 101, which has
      an anticoagulant effect and also inhibits platelet aggregation, seems to be
      useful for the treatment and prevention of chronic arterial occlusion when
      combined with drugs such as anticoagulants, antiplatelet agents, and
      vasodilators.

PMID- 1977337
TI  - Effect of magnesium chloride on rabbit bronchial smooth muscle.
AB  - STUDY OBJECTIVE: The objective of this study was to determine the extent to which
      magnesium relaxes bronchial smooth muscle during induced contraction. DESIGN: An
      in-vitro model using bronchial rings from New Zealand White rabbits stimulated to
      contract by electrical stimulation, histamine, or bethanechol. INTERVENTIONS:
      Magnesium chloride 1, 6, 16, 36, and 86 mM was added to each tissue bath and
      resting tension was measured. Electrical stimulation 100 V/100 ms, histamine 10
      mM, or bethanechol 6.25 mM was added to washed tissues to induce contraction.
      This was followed with magnesium chloride 5, 10, and 50 mM, and the response of
      bronchial smooth muscle was measured. MEASUREMENTS AND MAIN RESULTS: Magnesium
      chloride 1, 6, 16, 36, and 86 mM decreased the mean +/- SEM resting tension of
      bronchial rings by 40 +/- 16, 100 +/- 11, 110 +/- 10, 170 +/- 9, and 275 +/- 22
      mg, respectively. Electrical stimulation (4) of 100 V/100 ms increased the mean
      +/- SEM resting tension by 168 +/- 52 mg. Magnesium chloride 5, 15, and 50 mM
      added to the tissue bath decreased the response to 100 V/100 ms to 65 +/- 27, 40
      +/- 23, and 1 +/- 0 mg, respectively. Histamine 10 mM (4) increased mean +/- SEM
      resting tension by 490 +/- 121 mg. Magnesium chloride 5, 15, and 50 mM decreased
      the histamine response by 80 +/- 56, 250 +/- 74, and 475 +/- 131 mg,
      respectively. Bethanechol 6.25 mM (14) increased the mean +/- SEM resting tension
      by 495 +/- 74 mg. Magnesium chloride (5, 15, 50 mM) decreased bethanechol-induced
      tension by 52 +/- 18, 184 +/- 26, and 506 +/- 64 mg, respectively. CONCLUSION:
      Magnesium chloride produced dose-dependent relaxation of bronchial smooth muscle
      at rest and when stimulated by histamine, bethanechol, or electrical impulse.
      Calcium chloride was unable to significantly reverse magnesium-induced
      relaxation. These data support the hypothesis that magnesium relaxes smooth
      muscle and dilates bronchial rings.

PMID- 1977338
TI  - Undergraduate education in emergency medicine.

PMID- 1977339
TI  - Whole-bowel irrigation as treatment for zinc sulfate overdose.
AB  - A 16-year-old boy ingested approximately 50 zinc sulfate tablets (ZnSO4; 500-mg
      tablets). After spontaneous emesis, ipecac-induced emesis, and orogastric lavage,
      an abdominal radiograph performed four hours after ingestion still demonstrated
      approximately 50 ZnSO4 tablets within the stomach and three pills within the
      colon. Whole-bowel irrigation was begun with a polyethylene glycol lavage
      solution (PEG; Golytely) that was administered through a nasogastric tube; within
      one hour, the patient began producing a rectal effluent that contained pills. The
      patient remained asymptomatic throughout whole-bowel irrigation. Stool guaiac
      tests were negative. The serum chloride, however, increased from 105 to 127
      mEq/L. Follow-up kidney, ureter, and bladder studies demonstrated the clearance
      of the zinc tablets from the gastrointestinal tract during the next 24 hours.

PMID- 1977340
TI  - Activated charcoal alone versus activated charcoal & ipecac.

PMID- 1977341
TI  - Cell Lineages in Development. Proceedings of the first Howard H. Holtzer
      Symposium in Developmental Biology. University of Pennsylvania, Philadelphia,
      Pennsylvania, May 5-6, 1989.

PMID- 1977342
TI  - Heteroreceptors, autoreceptors, and other terminal sites.

PMID- 1977343
TI  - Presynaptic receptors and the question of autoregulation of neurotransmitter
      release. A conference. December 4-6, 1989, Philadelphia, Pennsylvania.
      Proceedings.

PMID- 1977344
TI  - Presynaptic muscarinic receptors in the central nervous system.

PMID- 1977345
TI  - Changes in cardiovascular responses of conscious rats to endogenous opioids
      following treatment with catecholamine-depleting agents.

PMID- 1977346
TI  - Dopamine autoreceptors. Biochemical, pharmacological, and morphological studies.

PMID- 1977347
TI  - Transmitter release from sympathetic nerve terminals on an impulse-by-impulse
      basis and presynaptic receptors.

PMID- 1977348
TI  - Pulse-to-pulse modulation of transmitter release in the central nervous system.
      Basic and pharmacological aspects.

PMID- 1977349
TI  - Prostaglandins and the release of the adrenergic transmitter.
AB  - Prostaglandins (PG) are synthesized from arachidonic acid, which is deesterified
      from tissue lipids in response to various stimuli including adrenergic
      transmitter, consequent to activation of one or more lipase(s). The profile of
      arachidonic acid metabolites generated in response to sympathetic nerve
      stimulation or administration of norepinephrine (NE) may vary in different
      tissues. For example, in the kidney and spleen, PGE2, is the major and PGI2 and
      PGF2 alpha the minor products; whereas in the heart and blood vessels, PGI2 is
      the principal product of arachidonic acid generated in response to sympathetic
      nerve stimulation. PGE2 and PGI2 inhibit release of NE and/or the postjunctional
      actions of this neurotransmitter in several tissues. These observations and the
      findings that inhibitors of cyclooxygenase enhance NE release and the response of
      effector organs to nerve stimulation suggest that PGs act as physiological
      modulators of adrenergic transmission. The mechanism by which PGs modulate
      release of the adrenergic transmitter has not yet been established. NE appears to
      be released from sympathetic fibers during depolarization by influx of Na+, which
      is associated with entry of Ca++ through omega-conotoxin-sensitive Ca++ channels
      that are distinct from those in the vascular smooth muscle, which are sensitive
      to nifedipine. Ouabain in low external K+ activates the former, whereas external
      Na+ depletion activates the latter type of Ca++ channels in the nerve fiber and
      promotes release of NE. PGs (PGE2) may inhibit release of NE from nerve fibers by
      interfering with the availability of Ca++ through these Ca++ channels or
      promoting efflux of Ca++ from the nerve terminal.

PMID- 1977350
TI  - Presynaptic receptors and autonomic effectors.
AB  - Agonist interactions with release processes do not validate autoreceptor
      operation. Instead, the data suggests that autoreceptors function as
      homoreceptors. Declining efficacy of agonist inhibition of transmitter release
      with increasing stimulation "intensity" is not assignable to competition with
      endogenous transmitter for a finite population of receptors. Heteroreceptor
      activation also reveals a pattern of declining efficacy with increasing
      intensity. Inhibition of stimulation-induced release by agonists also does not
      correlate inversely with that of antagonist effectiveness, as it should if both
      effects are linked to biophase levels of transmitter. Further, per pulse release
      of transmitter, in the absence of drugs, does not comply with expectations for
      autoinhibition. Experiments with tetrodotoxin, and study of the magnitudes of
      agonist and antagonist effects suggest that in the periphery putative
      autoreceptors may actually be homoreceptors, e.g., sympathetic nerve terminal
      receptors responsive to circulating catecholamines. In the central nervous system
      the paracrine secretion of transmitter may invoke homoreceptor activation rather
      than autoreceptors. Such activation may include, for example, the release of
      adrenaline from one set of fibers in the hypothalamus to act on dopaminergic or
      noradrenergic fibers or the release of noradrenaline from the terminals of some
      noradrenergic fibers in the cortex to activate alpha2 receptors on other cortical
      noradrenergic fibers, the latter with a somewhat different function in the same
      brain region. The action of antagonist drugs to enhance transmitter release may
      be direct on nerve membranes in particular on sodium channels, and often
      unrelated to feedback regulation. This possibility is discussed by me elsewhere
      in this volume. It is shown that yohimbine and a low concentration of veratridine
      have similar and nonadditive effects on transmitter release.

PMID- 1977351
TI  - On the role of adenylate cyclase in presynaptic modulation of neurotransmitter
      release mediated by monoamine and opioid receptors in the brain.

PMID- 1977352
TI  - Presynaptic receptors and modulation of noradrenaline and ATP secretion from
      sympathetic nerve varicosities.
AB  - Our results in the model tissues examined show (1) that alpha 2 agonist(s)
      depressed the secretion of NA and ATP caused by nerve stimulation at low
      frequency, (2) that the secretion of both NA and ATP was moderately
      autoinhibited, under conditions when endogenous NA was shown to accumulate
      extracellularly, (3) that a K+ channel blocking agent increased much more
      strongly than alpha 2-adrenoceptors block the secretion of both NA and ATP, and
      also amplified enormously the NA-mediated neurogenic contraction, (4) that,
      therefore, a high K+ efflux is likely to be much more important than alpha 2
      adrenoceptor-mediated autoinhibition for maintaining a low release probability in
      sympathetic nerve varicosities, and (5) that the alpha 2-adrenoceptor agonist,
      clonidine, or the Ca2+ channel blocking agent, Cd2+, inhibited transmitter
      secretion, at least in part, via targets "upstream" of the varicosity.

PMID- 1977353
TI  - Presynaptic modulation of sympathetic neurotransmitter release by modulators of
      cyclic 3',5'-guanosine monophosphate in canine vascular smooth muscle.

PMID- 1977354
TI  - Presynaptic receptors. Relevance to psychotropic drug action in man.

PMID- 1977355
TI  - Presynaptic peptide receptors and hypertension.

PMID- 1977357
TI  - The problem with autoreceptors.
AB  - There are numerous problems with the concept that antagonists enhance transmitter
      release by blockade of feedback. It was shown that antagonist enhancement of
      transmitter release does not correlate satisfactorily with the intensity of
      stimulation or with other indices of biophase transmitter concentration. Wide
      variations were shown to exist between antagonists in the amount of enhancement
      of release they induce. Also, antagonists enhance transmitter release or the
      effector response with a single stimulation pulse, a condition under which no
      feedback is possible. A study of agonist/antagonist relationships indicates
      different sites of action, and it was determined that the antagonist effect has
      negligible or minimal latency and that enhancement by antagonists is maximal
      under minimal condition of stimulation. Antagonists were shown to enhance release
      by a direct action, not by passive occupancy of agonist sites. Experiments were
      described in which acetylcholine and cold selectively antagonized antagonist but
      not agonist effects. Further, experiments with pulse duration shifts and with
      veratridine pointed to a direct action of antagonists on Na+ (also Ca++?) channel
      gating mechanisms, which results in a shift in the voltage dependence of
      activation. If antagonists, in some particular instances, enhance release by
      blockade of sites involved in negative feedback this is likely lost or mired in
      their more prominent direct actions on neurosecretion--and these must be sorted
      out. The acceptance of the fact that antagonists act directly to alter
      transmitter release (and not only as passive occupiers of presynaptic receptors),
      as the present study shows, both in the central nervous system and in the
      periphery, opens a new area for future investigation, and may be exploitable for
      therapeutic purposes and to gain an enriched understanding of the mechanism of
      neurosecretion.

PMID- 1977356
TI  - The physiological operation of presynaptic inhibitory autoreceptors.

PMID- 1977358
TI  - In vivo electrophysiology of central nervous system terminal autoreceptors.

PMID- 1977359
TI  - In vivo evidence for the existence of autoreceptors on dopaminergic,
      serotonergic, and cholinergic neurons in the brain.
AB  - Intrastriatal infusions as well as systemic administration of the selective D-2
      antagonist (-)-sulpiride caused similar increases in the dialysate levels of
      dopamine (DA) to about 180% of controls. A similar conclusion was drawn when the
      selective D-2 agonist (-)-N-0437 was infused intrastriatally or administered
      systemically: both routes of administration caused a decrease in the release of
      DA to about 40-50% of controls. In order to evaluate the properties of synthesis
      modulating autoreceptors on dopaminergic and serotonergic neurons we have
      estimated the synthesis rate of serotonin (5-HT) or DA by monitoring the 5-HTP or
      DOPA formation in the dialysates during infusion of a decarboxylase inhibitor.
      Infusion of (-)-N-0437 decreased the DOPA formation, whereas infusion of (-)
      sulpiride increased the dialysate levels of DOPA; these results indicate that the
      D-2 receptors controlling the synthesis of DA are localized on nerve terminals.
      Administration of the selective 5-HT-IA agonist 8-hydroxy-dipropyl-aminotetraline
      (8-OH-DPAT) resulted in a decrease in the synthesis rate of 5-HT. When 8-OH-DPAT
      was infused via the dialysis membrane, the agonist was unable to modify the
      release of 5-HT. The effects of infusion of the muscarinic agonist oxotremorine
      and the muscarinic antagonist atropine were dependent on the presence of the
      esterase inhibitor neostigmine in the perfusion fluid. In the absence of
      neostigmine, oxotremorine caused a pronounced decrease in the output of
      acetylcholine (ACh), whereas atropine was without effect. In the presence of
      neostigmine oxotremorine was without effect but infusion of atropine or other
      anticholinergics caused a pronounced increase in the dialysate levels of ACh. It
      is concluded that the autoreceptor controlling the release of ACh is of the M3
      type and that the receptor is not fully occupied during normal conditions. In
      conclusion, microdialysis of neurotransmitters is a valuable tool for the study
      of autoreceptors in vivo. The presented studies provided evidence for the
      existence of autoreceptors controlling the synthesis and/or release of DA, 5-HT,
      as well as ACh in the striatum.

PMID- 1977360
TI  - Modulation of noradrenaline release by activation of presynaptic beta
      adrenoceptors in the cardiovascular system.
AB  - Peripheral sympathetic nerve terminals in many tissues, but not all, are endowed
      with beta-adrenoceptors. Activation of these result in an enhancement of
      noradrenaline release evoked by electrical nerve stimulation. These so-called
      presynaptic beta-adrenoceptors are possibly located on the outer surface of the
      varicosity of the noradrenergic nerves. A postsynaptic location, however, is also
      a possibility. The presynaptic beta-adrenoceptors appear to be of the beta 2
      adrenoceptor subtype. However, specific classification is lacking. The
      stereospecificity of the beta-adrenoceptors is controversial. These receptors are
      not activated by noradrenaline released from sympathetic nerves. Adrenaline
      derived from the adrenal medulla may be the physiological activator. Either
      circulating adrenaline or adrenaline taken up by sympathetic nerve terminals and
      then released as a cotransmitter with noradrenaline activates the presynaptic
      beta-adrenoceptors. In the latter case, a "positive" feedback" loop may be
      formed.

PMID- 1977361
TI  - Presynaptic receptors in the neuromuscular junction.

PMID- 1977362
TI  - The ionic basis of inhibitory presynaptic modulation and substance B.
AB  - We have investigated the possibility that, regardless of the involvement of a
      second messenger system, the ultimate effect of presynaptic, receptor-activated
      inhibitory modulation is the opening of a K channel. This possibility was
      explored utilizing rat cortical synaptosomes that were prelabeled with either
      86Rb or [3H]acetylcholine, depolarizing with either K+ or veratridine, and
      measuring either efflux of 86Rb or release of [3H]acetylcholine in the presence
      or absence of inhibitory presynaptic modulators. The modulating agents used were
      2-chloroadenosine, carbamylcholine, clonidine, and morphine. In all instances,
      these agents promoted an increased efflux of 86Rb, indicating hyperpolarization,
      and decreased release of acetylcholine. These results support our contention that
      an increase in K conductance may be responsible for presynaptic inhibition of the
      release of neurotransmitters. We have also found that substance B, a compound
      that reverses presynaptic modulation, appears to act by closing K channels.

PMID- 1977363
TI  - Use of radionuclides in clinical endocrinology.
AB  - Radionuclides provide sensitive reporter molecules for labeling pharmaceuticals.
      Hormone measurements using radioimmunoassays are commonplace today, increasing
      our understanding of the pathophysiology of endocrine disease. In turn, hormones
      tagged with radionuclides are opening studies on new fields of receptor defects
      both at the receptor site and beyond. Common disorders such as diabetes mellitus,
      hyperthyroidism and acromegaly have been the first to benefit. Tracer methods to
      study secretory and clearance rates and the size of metabolic pools are mainly
      based on the use of radionuclides. DNA probes are useful in unravelling endocrine
      defects at the genome level. Originally using radioiodine but now an increasing
      number of newly synthesised radiopharmaceuticals, the individual organs are being
      visualised more specifically. Among these agents are labelled monoclonal
      antibodies hunting for neoplasias and analogs of adrenal medullary hormones such
      as metaiodobenzylguanidine (MIBG). From these studies the therapy of endocrine
      disorders will ultimately benefit.

PMID- 1977364
TI  - Isolation of a cDNA probe for the human intestinal dipeptidylpeptidase IV and
      assignment of the gene locus DPP4 to chromosome 2.
AB  - We report the nucleotide sequence and derived amino-acid sequence of a cDNA clone
      encoding the 3' end of human intestinal dipeptidylpeptidase IV (DPP-IV). This
      cDNA probe identifies a 4 kb mRNA in the human colon cancer cell line Caco-2. We
      demonstrate here an extensive homology between this human DPP-IV cDNA and the
      recently published rat liver DPP-IV cDNA. Using the human DPP-IV cDNA to probe
      genomic DNA from a panel of somatic cell hybrids we have assigned the gene
      encoding human DPP-IV to chromosome 2.

PMID- 1977365
TI  - Abstracts of the Third International Conference of Anticancer Research. October
      16-20, 1990, Marathon, Greece.

PMID- 1977366
TI  - Cure of Trypanosoma brucei brucei and Trypanosoma brucei rhodesiense infections
      in mice with an irreversible inhibitor of S-adenosylmethionine decarboxylase.
AB  - A structural analog, 5'-([(Z)-4-amino-2-butenyl]methylamino)-5'-deoxy adenosine
      (MDL 73811), of decarboxy S-adenosyl-L-methionine, the product of the reaction
      catalyzed by S-adenosyl-L-methionine (AdoMet) decarboxylase (DC), was found to
      inhibit Trypanosoma brucei brucei AdoMet DC. The inhibition was time dependent
      (tau 50, 0.3 min), exhibited pseudo-first-order kinetics (Ki, 1.5 microM), and
      was apparently irreversible. The natural substrate of the reaction, AdoMet,
      protected the enzyme from inactivation, suggesting that MDL 73811 was directed at
      the enzyme active site and was probably catalytically activated. Administration
      of MDL 73811 to T. b. brucei-infected rats resulted in rapid inhibition of AdoMet
      DC activity, a decrease in spermidine, and an increase in putrescine in the
      trypanosomes isolated from treated rats. Treatment of T. b. brucei-infected mice
      with MDL 73811 (20 mg/kg of body weight intraperitoneally twice daily for 4 days)
      resulted in cures of the trypanosome infections. Additionally, drug-resistant T.
      brucei rhodesiense infections in mice were cured by either a combination of MDL
      73811 (50 mg/kg intraperitoneally three times per day for 5 days) and relatively
      low oral doses of alpha-difluoromethylornithine or MDL 73811 (50 mg/kg per day
      for 7 days) administered alone in implanted miniosmotic pumps. These data suggest
      that MDL 73811 and, perhaps, other inhibitors of AdoMet DC have potential for
      therapeutic use in various forms of African trypanosomiasis.

PMID- 1977368
TI  - Nevus cells of nerve sheath origin?

PMID- 1977367
TI  - Abnormal essential fatty acid metabolism in Darier's disease.
AB  - Fatty acid levels in plasma and erythrocyte cell membranes were determined in 13
      Danish patients with Darier's disease and 21 Danish controls. Concentrations of
      the main dietary essential fatty acids, linoleic acid (18:2n-6) and alpha
      linolenic acid (18:3n-3), were consistently modestly above normal; concentrations
      of the delta 6-desaturase metabolites of both linoleic and alpha-linolenic acids,
      however, were consistently and often significantly below normal. These results
      suggest that the capacity of the enzyme delta 6-desaturase activity is inadequate
      in patients with Darier's disease.

PMID- 1977369
TI  - Observations on the seasonal incidence and diel oviposition periodicity of
      Haemagogus mosquitoes (Diptera: Culicidae) in Trinidad, W.I. II. Haemagogus
      equinus Theobald.
AB  - Diel patterns of oviposition of sylvan Haemagogus equinus in the field in
      Trinidad, West Indies, were monitored weekly for 53 consecutive weeks using
      standard ovitraps. During the wet season (September to November 1981 and May to
      September 1982) a large well-defined unimodal peak (comprising 97% of all eggs
      laid and 89% of occurrences) occurred at 12.00-14.00 hours, four to six hours
      before sunset. During the dry season (December 1981 to May 1982), two small less
      well-defined peaks occurred at 10.00-12.00 and 14.00-16.00 hours (comprising 4.9%
      of eggs laid and 14% of occurrences). A diurnal oviposition pattern was observed
      when the wet and dry season data were combined. The number of eggs and
      occurrences found during the wet season was significantly higher (P greater than
      0.001) than that observed during the dry season.

PMID- 1977370
TI  - A prospective, multicenter study of patients' refusal of antipsychotic
      medication.
AB  - Refusal of treatment with antipsychotic medication was studied prospectively in a
      sample of 1434 psychiatric patients admitted to four acute inpatient units in
      state-operated mental health facilities in Massachusetts during a 6-month period.
      Compared with a control group of patients who accepted prescribed antipsychotic
      treatment, the 103 patients who refused were older, of a higher social class, and
      less likely to have been prescribed antiparkinsonian medications. On admission,
      prior to refusal of medication, patients who refused were found to have
      significantly higher Brief Psychiatric Rating Scale scores than compliant
      patients and more negative attitudes regarding their hospitalization and past,
      present, and future treatment. Treatment refusal had negative effects on the
      hospital milieu and on the patient; refusers were more likely to require
      seclusion or restraint and had longer hospitalizations than treatment acceptors.
      Most refusal episodes ended with voluntary acceptance of treatment. In 23% of
      cases medications were discontinued. Only 18% of the sample reached formal,
      judicial review, and in every case that did, involuntary treatment was ordered.
      The policy implications of these findings are discussed.

PMID- 1977372
TI  - [Proceedings of the VIII All-Union Congress of Pathologists (October 17-21,
      Tbilisi, 1989].

PMID- 1977371
TI  - Prednisone effects on neurochemistry and behavior. Preliminary findings.
AB  - To evaluate the neurochemical, neuroendocrine, and behavioral effects of
      exogenous corticosteroids in humans, we administered prednisone (80 mg/d orally
      for 5 days) in a double-blind manner to 12 medically healthy volunteers.
      Behavioral measures were assessed before, during, and after prednisone
      administration in all 12 subjects, and cerebrospinal fluid biochemistry was
      assessed before and during prednisone administration in 9 of the subjects.
      Prednisone administration was associated with decreases in cerebrospinal fluid
      levels of corticotropin, norepinephrine, beta-endorphin, beta-lipotropin, and
      somatostatinlike immunoreactivity. No significant changes were noted in
      cerebrospinal fluid levels of alpha-melanocyte-stimulating hormone, corticotropin
      releasing hormone, 3-methoxy-4-hydroxyphenylglycol, homovanillic acid, or 5
      hydroxyindoleacetic acid. No consistent or significant group mean changes were
      observed in structured behavioral ratings, although 9 (75%) of the volunteers
      studied reported mild behavioral changes while receiving prednisone. Correlations
      between the neurochemical and behavioral changes are discussed.

PMID- 1977373
TI  - Mae III positively detects the mitochondrial mutation associated with type I
      Leber's hereditary optic neuropathy.
AB  - Leber's hereditary optic neuropathy is a blinding disease that usually causes
      acute or subacute central visual loss in adolescent and young adult males. In
      patients who lack a family history of a similar illness, Leber's disease has been
      a diagnosis of exclusion. The recent discovery of a specific mitochondrial
      mutation in many pedigrees affected with the disease has provided the basis for
      rapid molecular diagnosis of one genetic type of Leber's disease. We have
      developed a new method, based on a Mae III (Boehringer Mannheim Biochemicals,
      Indianapolis, Ind) restriction fragment length polymorphism, for detecting the
      Wallace-type Leber's mutation. The method has several advantages over the
      previously used SfaN I method that make it more suitable for use as a general
      laboratory test. We demonstrate the utility of this new test in the diagnosis of
      Leber's disease in a patient with no family history of visual loss.

PMID- 1977374
TI  - Unpleasant and anticonflict effects of nicotine observed by conditioned taste
      aversion and hypertonic NaCl solution tests in mice.
AB  - Effects of subcutaneously (s.c.) administered nicotine on preference for 0.1%
      saccharin solution and rejection for hypertonic (2%) NaCl solution were
      investigated in water-deprived mice. The results were compared with those after
      s.c. administration of methamphetamine, caffeine and morphine. When nicotine 0.3
      and 1 mg/kg, methamphetamine 0.5, 1 and 2 mg/kg, and caffeine 30 mg/kg were
      administered to mice immediately after intake of the saccharin solution, they
      exhibited a significant decrease in the preference for saccharin solution on the
      next day (namely conditioned aversion), even though no drug administration was
      carried out. However, 2.5-10 mg/kg of morphine produced no marked change in the
      preference. Daily administration for 5 days of nicotine 1 mg/kg, methamphetamine
      2 mg/kg, caffeine 30 mg/kg, and morphine 10 mg/kg did not produce any marked
      change in the individual drug effects on the conditioned taste aversion. On the
      other hand, rejection for the hypertonic NaCl solution was significantly
      attenuated when nicotine 0.3 mg/kg was administered prior to the experiment,
      probably showing an anticonflict effect. Caffeine 10 mg/kg, and morphine 2.5 and
      5 mg/kg also attenuated the rejection for hypertonic NaCl solution. In contrast,
      methamphetamine 0.25-2 mg/kg enhanced the rejection in a dose-dependent manner.
      The present results suggest that, in spite of the same dose, nicotine shows both
      unpleasant and anticonflict (antianxiety) effects dependent on the environmental
      situation such as stimulus, timing of the drug administration etc. Furthermore,
      it is notable that the effects of nicotine observed in our experiments were
      similar to those of caffeine.

PMID- 1977375
TI  - The use and abuse of minor tranquillisers.
AB  - The author briefly outlines the benefits of benzodiazepines and also notes their
      risks. The usefulness of tricyclic antidepressants as an alternative to long-term
      benzodiazepines is emphasised.

PMID- 1977376
TI  - Expression of c-erbB-2 protein detected in adenocarcinoma arising from parotid
      pleomorphic adenoma.
AB  - The c-erbB-2 proto-oncogene is known to encode a 185,000 molecular weight
      glycoprotein. This protein has been detected immunohistochemically in several
      human adenocarcinomas, suggesting that it may play a role in the development of
      these malignancies. In the otolaryngological field none of the adenocarcinomas
      expressing c-erbB-2 protein has yet been described. In this article we presented
      a case of parotid adenocarcinoma expressing the c-erbB-2 protein. In this case
      the adenocarcinoma was thought to have originated from pleomorphic adenoma.
      Immunohistochemically, the adenocarcinoma cells were stained and the remaining
      pleomorphic adenoma cells were not stained by polyclonal antibody against the c
      erbB-2 protein. The expression of c-erbB-2 protein may have been related to the
      malignant development of the pleomorphic adenoma.

PMID- 1977377
TI  - Preventive strategies in management of acute myocardial infarction.
AB  - Recent studies on pathogenetic mechanisms, supplemented by findings in clinical
      trials point the way to a logical approach to acute evolving myocardial
      infarction. This is designed in the earliest stage to limit infarction through
      reduction in myocardial oxygen demands, improvement in collateral blood supply
      and dissolution of coronary thrombus, to prevent in a later stage coronary
      reocclusion through administration of antiplatelet agents, and then to prevent
      infarct expansion through reduction in ventricular wall tension throughout the
      period of repair. Application of such an approach holds the promise of reducing
      infarct size and all the complications of infarction, as well as short and long
      term mortality. The approach is active and aggressive, and contrasts with the
      approach applied a decade ago, where infarction was accepted as inevitable and
      therapies were reserved for managing its complications.

PMID- 1977378
TI  - Antigenic stability of fimbriae of Bacteroides nodosus.
AB  - Successful vaccination of sheep against footrot and attempts to eradicate the
      disease depend on there being a limit to the antigenic diversity of the causative
      bacterium, Bacteroides nodosus. Fimbrial antigenic variation was therefore
      investigated in vivo, both under conditions of chronic infection and under the
      pressure of a vaccine-induced immune response, to ascertain whether this
      represented an obstacle to such goals. Material was available from 5 experiments
      and although B. nodosus appeared to have undergone changes in its fimbrial
      antigens in one of these, the possibility that superinfection was responsible for
      the variation detected could not be ruled out because all sheep in this case were
      maintained at pasture. Overall, the results provided no evidence of fimbrial
      antigenic shift in B. nodosus in vivo and in conclusion, the survival of the
      organism in the sheep's foot, both in long-term natural infection and following
      vaccination, must therefore be related to factors other than the ability to
      undergo antigenic variation in order to evade the host's immune response.

PMID- 1977379
TI  - Examination of a backchaining/counterconditioning process during the extinction
      of conditioned fear.
AB  - Two experiments using rat subjects are reported which attempt to delineate the
      theoretical mechanisms involved in exposure/extinction procedures that are used
      to eliminate conditioned fear. In Experiment 1, a within-subjects design was
      employed to study the temporal course of the extinction process by examining the
      relationship among three separate measures of classically conditioned fear-
      suppression of an ongoing, operant behavior during the nonreinforced fear
      eliciting CS presentation, the time to the first response during this CS
      presentation, and the time to recover responding following termination of the CS.
      The results indicated a temporal relationship among these measures, both within
      and across nonreinforced CS trials, which were considered to reflect a
      backchaining of a fear-antagonistic response during extinction, and provided an
      empirical demonstration of an extinction process consistent with Denny's
      (Behaviour Therapy and Experimental Psychiatry, 7, 315-321, 1976)
      elicitation/backchaining explanation of extinction. Experiment 2 attempted to
      manipulate the course of extinction and the temporal relationship among these
      three fear measures through the paired presentations of the fear CS with a
      palatable substance (maltose). This procedure produced greater extinction
      apparently by facilitating the backchaining process. These results are discussed
      with implications for exposure-based therapies.

PMID- 1977380
TI  - Effects of diazepam on approach, self-reported fear and psychophysiological
      responses in snake phobics.
AB  - The effects of diazepam was assessed on a number of measures of phobic anxiety.
      Snake-phobic subjects underwent two sessions on either diazepam or placebo in a
      crossover design. In addition to a habituation series, a slide with the phobic
      object was displayed as well as a live snake which subjects were asked to
      approach. The anxiolytic effect of diazepam was manifest in only one measure of
      fear, namely self-rated fear at the point of closest approach when it also
      attained the highest level. The result would indicate that diazepam has an
      anxiolytic only on high levels of subjective anxiety. The magnitude of the phasic
      cardiac reaction to the slide was highly and positively correlated with self
      rated fear of the slide.

PMID- 1977381
TI  - Is agoraphobia harder to treat? A comparison of agoraphobics' and simple phobics'
      response to treatment.
AB  - Agoraphobia is reputed to be more difficult to treat than simple phobia. In a
      test of this supposition, 38 agoraphobics and 19 simple phobics were each given
      10 sessions of graduated in vivo exposure. They were assessed before and after
      therapy using a behavioral avoidance test, behavioral diaries, and self-report
      measures. Analysis of covariance revealed unequivocal posttest differences only
      on self-assessed disability level; agoraphobics had changed less in their report
      of global disability immediately following treatment but not at follow-up. Sixty
      eight percent of the simple phobics showed clinically significant improvement on
      avoidance of the Main Phobia, compared with 34% of the agoraphobics. On three
      other outcome measures, including more precise behavioral measures of phobia,
      agoraphobics and simple phobics responded equivalently to treatment. Given
      clinicians' impression about the comparative difficulty in treating agoraphobic
      clients, fewer differences in treatment response were obtained than were
      expected. Several possible explanations for this discrepancy are discussed.

PMID- 1977382
TI  - Identification and characterization of the major stilbene-disulphonate- and
      concanavalin A-binding protein of the porcine renal brush-border membrane as
      aminopeptidase N.
AB  - A 130 kDa glycoprotein (GP 130) was purified from porcine renal brush-border
      membranes by affinity chromatography using immobilized 4-acetamido-4'
      isothiocyanostilbene-2,2'-disulphonate (SITS)- and concanavalin A-Sepharose. GP
      130 was the major concanavalin A-binding protein in porcine renal brush-border
      membranes and also bound Ricinus communis (castor-bean) and wheat-germ
      agglutinins. Endo-beta-N-acetylglucosaminidase F reduced the molecular mass of GP
      130 by 20 kDa as determined by SDS/PAGE, whereas endo-beta-N
      acetylglucosaminidase H reduced the molecular mass by 5 kDa, showing that GP 130
      contained both complex and high-mannose carbohydrate structures. Western-blot
      analyses using an antibody raised against GP 130 showed that it was localized to
      the brush-border membrane fraction and was present in a membrane fraction of the
      pig kidney cell line LLC-PK1. The N-terminal sequence and amino acid composition
      of GP 130 showed that GP 130 is similar to rat kidney zinc peptidase and human
      intestinal aminopeptidase N. GP 130 had aminopeptidase N enzymic activity and was
      inhibited by bestatin (Ki = 36 microM), 1,10-phenanthroline (Ki 30 microM), Zn2+
      (Ki 26 microM), Cu2+ (Ki 260 microM), pre-incubation with EDTA and by a
      polyclonal antibody against GP 130. Bicarbonate and iodide blocked the binding of
      GP 130 to the SITS-affinity resin, showing that GP 130 has an anion-binding site.
      Neither these anions nor stilbene disulphonates affected the aminopeptidase N
      activity of GP 130.

PMID- 1977384
TI  - Human immunodeficiency virus I-induced expression of P-glycoprotein.
AB  - Because prolonged treatment of HIV infection with 3'-azido-3'-deoxythymidine
      (AZT) is associated with in vitro resistance to AZT, we examined whether HIV
      could induce/amplify the expression of p-glycoprotein in infected cells resulting
      in reduced drug accumulation leading to reduced sensitivity to AZT. We show that
      both H9 (T cell line) and U937 (monocytic cell line) cells, upon infection with
      HIV, expressed increased levels of P-glycoprotein and accumulated significantly
      less AZT and daunorubicin as compared to uninfected cells. Sodium azide increased
      intracellular accumulation of daunorubicin in infected cells, suggesting a
      metabolically active drug efflux mechanism. Addition of cyclosporin A partially
      corrected intracellular drug accumulation in HIV infected cells. In addition,
      similar to multidrug resistant tumor cells, HIV-infected cells show
      depolarization of plasma membrane. Taken together, these data suggest that HIV
      induced increased P-glycoprotein expression could be one of the mechanisms for
      reduced intracellular accumulation of antiviral agents and resistance to AZT and
      perhaps to other anti-retroviral agents.

PMID- 1977383
TI  - Phorbol ester-stimulated phosphorylation of keratinocyte transglutaminase in the
      membrane anchorage region.
AB  - The membrane-bound transglutaminase of cultured keratinocytes became
      radioactively labelled upon addition of [32P]Pi to the medium. Transglutaminase
      phosphorylation was also demonstrable using particulate material isolated from
      cell homogenates. Compatible with mediation of the labelling by protein kinase C,
      the degree of phosphorylation in intact cells was stimulated approx. 5-fold in 4
      h on treatment with the tumour-promoting phorbol ester phorbol 12-myristate 13
      acetate, but not by phorbol. The extent of labelling was virtually unaffected by
      cycloheximide inhibition of protein synthesis, indicating that it arose primarily
      through turnover of phosphate in the membrane-bound enzyme. Phosphoamino acid
      analysis detected labelling only of serine residues. Most of the label was
      removed by trypsin release of the enzyme from the particulate fraction of cell
      homogenates, which deletes a membrane anchorage region of approximately 10 kDa.
      Upon trypsin treatment of the enzyme after immunoprecipitation, the phosphate
      label was recovered in soluble peptide material with a size of several thousand
      Da or less. Indicative of fragmentation of the membrane anchorage region, this
      material was separable by h.p.l.c. into two equally labelled peptides. Moreover,
      when the enzyme was labelled with [3H]palmitate or [3H]myristate, the fatty-acid
      labelled peptide material required non-ionic detergent for solubilization and was
      separable from the phosphate-labelled material by gel filtration. Phorbol ester
      treatment of cultured keratinocytes in high- or low- Ca2(+)-containing medium was
      not accompanied by an appreciable protein-synthesis-independent change in
      transglutaminase activity. Independent of possible alteration of the intrinsic
      catalytic activity of the enzyme, phosphorylation may well modulate its
      interaction with substrate proteins, a potential site for physiological
      regulation.

PMID- 1977385
TI  - Stimulatory actions of bioflavonoids on tyrosine uptake into cultured bovine
      adrenal chromaffin cells.
AB  - The effects of flavonoids on L-[14C]tyrosine uptake into cultured adrenal
      chromaffin cells were examined. Flavone markedly stimulated tyrosine uptake into
      these cells in a manner dependent on its concentration. Apigenin also caused a
      moderate stimulatory action, but quercetin had no significant effect on the
      uptake. Flavone also stimulated the uptake of histidine, but did not affect the
      uptake of serine, lysine, or glutamic acid. These results are considered to
      propose the possibility that flavonoids may be able to stimulate the precursor
      uptake into the cells, resulting in an enhancement of the biogenic amine
      production.

PMID- 1977386
TI  - Inhibitors of IMP dehydrogenase stimulate the phosphorylation of the antiviral
      nucleoside 2' ,3'-dideoxyguanosine.
AB  - The inosinate dehydrogenase (IMPD) inhibitors ribavirin, tiazofurin and
      mycophenolic acid were found to stimulate by as much as 20-fold the anabolism of
      the anti-HIV agent 2' ,3'dideoxyguanosine to its 5'-diphosphate (ddGDP) in a
      human T-cell culture system (Molt-4 cells). Stimulation of the further conversion
      to ddGTP (the active form of the drug) was lesser in magnitude but still highly
      significant (up to 4-fold at appropriate concentrations of ribavirin or
      tiazofurin). In parallel with these increases, the inhibitors also produced
      increases of up to 35-fold in IMP levels. These results support the proposal that
      the initial phosphorylation of ddGuo is catalyzed by a phosphotransferase (5'
      nucleotidase) which utilizes IMP as its phosphate donor (Johnson and Fridland,
      [1989] Molec. Pharmacol. 36, 291-295). Concomitant with this increase in 5'
      phosphorylation of ddGuo, an increase in its anti-HIV activity of up to 6.5-fold
      was observed when this agent was combined with ribavirin (5 microM) in the H9
      [corrected] cell assay system.

PMID- 1977387
TI  - Somatostatin pretreatment facilitates GRF-induced GH release and increase in free
      calcium in pituitary cells.
AB  - Somatostatin pretreatment sensitizes rat anterior pituitary to hGRF stimulation
      in vitro. The pretreatment (1 nM for 10 min) facilitated GH release response of
      dispersed rat anterior pituitary cells to hGRF (1 nM for 3 min) 2.04-fold in a
      perifusion system. The effect lasted even 20 min after the pretreatment. SRIF
      pretreatment decreased cAMP content in the cells after hGRF stimulation to 61% of
      the control value. When hGRF was replaced by 1 mM DBcAMP and 15 mM KCl, the
      pretreatment increased GH secretion 1.69- and 1.67-fold respectively. SRIF
      pretreatment (1 nM for 10 min) caused a larger increase in (Ca2+)i by hGRF than
      that of control. The effect of SRIF pretreatment facilitates GRF-induced increase
      in GH secretion probably through the stimulation of increase in (Ca2+)i.

PMID- 1977389
TI  - Direct oxidation of glutamate by mitochondria from porcine adrenal cortex.
AB  - 1. Mitochondria isolated from porcine adrenal cortex under State 3 conditions
      oxidized succinate with a rate of 47 +/- 4.48 na oxygen/min/mg/protein and with
      ADP:O ratio 0.98 +/- 0.09. In the presence of 15 microM deoxycorticosterone the
      rate of succinate oxidation was 36.8 +/- 3.08 na oxygen/min/mg/protein. 2. Under
      the same conditions the rate of glutamate oxidation was 22.8 +/- 2.21 and 16.8 +/
      0.65 na oxygen/min/mg/protein, respectively. ADP:O ratio was 1.45 +/- 0.14. 3.
      Introduction of trace amounts of malate into the mitochondria oxidizing glutamate
      only slightly increased the rate of O2 uptake. 4. The glutamate dehydrogenase
      activity in these mitochondria was 12.5 +/- 0.69 nmol/min/mg.

PMID- 1977388
TI  - The primary structure of rat ribosomal protein L12.
AB  - The covalent structure of the rat 60S subunit protein L12 which is a component of
      the ribosomal elongation factor binding domain was deduced from the sequence of
      nucleotides in a recombinant cDNA and confirmed from the NH2-terminal amino acid
      sequence of the protein. L12 has 165 amino acids and a molecular weight of
      17,834. Hybridization of the cDNA to digests of nuclear DNA suggests that there
      are 11-13 copies of the L12 gene. The mRNA for the protein is about 800
      nucleotides in length. Rat L12 is homologous to Saccharomyces cerevisiae L15. The
      cDNA contains the highly repetitive DNA sequence, R.dre.1, in the 3' noncoding
      region.

PMID- 1977390
TI  - Effect of adrenergic and Ca2+ antagonists on increased ornithine decarboxylase
      expression in regenerating rat liver.
AB  - Partial hepatectomy (PH) (70% resection) causes within 4 hr an accumulation of
      ornithine decarboxylase (EC 4.1.1.17, ODC) mRNAs concomitant with an increase in
      ODC activity, maximum values being observed at 8 and 16 hr, respectively. In the
      early hours of hepatic regeneration, enhancement of transcriptional-rate of ODC
      gene, demonstrated by nuclear run-on analysis, can account for the accumulation
      of ODC mRNAs. The involvement of catecholamines in these processes is
      demonstrated by using prazosin and propranolol, specific antagonists of alpha 1
      and beta adrenoceptors, respectively. Prazosin reduces almost completely the rise
      of ODC activity at 4 hr, without affecting mRNA levels. At 16 hr, enzyme activity
      and mRNAs increase, however, over the values observed in regenerating liver of
      prazosin-untreated animals. These findings suggest that alpha 1-receptor
      activation triggers positive control signals for ODC gene expression at the early
      time of liver regeneration and, on the contrary, negative signals at later times
      by mainly post-transcriptional and transcriptional mechanisms, respectively.
      Propranolol reduces similarly the initial 4 hr-rise of ODC activity. These
      results indicate that activation of both alpha 1- and beta-adrenoceptors causes
      the large increase in ODC activity. Pharmacological manipulation of intracellular
      Ca2+ levels by verapamil, a Ca2(+)-channel blocker, or neomycin, an inhibitor of
      Ca2+ release from endogenous stores, diminishes ODC activity at 4 and 16 hr after
      PH. ODC mRNA levels, which are not modified at 4 hr, increase over the values of
      partially hepatectomized rat liver at 16 hr. Trifluoperazine inhibits both ODC
      activity and mRNA accumulation at the times studied. As a working hypothesis it
      is proposed that Ca2(+)-mediated processes induced by catecholamines are involved
      in ODC gene expression during the prereplicative phase of liver regeneration.

PMID- 1977391
TI  - The comparative efficacy and toxicity of second-line drugs in rheumatoid
      arthritis. Results of two metaanalyses.
AB  - We performed 2 metaanalyses of placebo-controlled and comparative clinical trials
      to examine the relative efficacy and toxicity of methotrexate (MTX), injectable
      gold, D-penicillamine (DP), sulfasalazine (SSZ), auranofin (AUR), and
      antimalarial drugs, the second-line drugs most commonly used to treat rheumatoid
      arthritis (RA). For the efficacy study, we applied a set of inclusion criteria
      and focused on trials which provided information on tender joint count,
      erythrocyte sedimentation rate, or grip strength. We found 66 clinical trials
      that contained 117 treatment groups of interest, and for each drug, we combined
      the treatment groups. For each outcome, results showed that AUR tended to be
      weaker than other second-line drugs. The results of the 3 outcome measures were
      synthesized into a composite measure of outcomes, and AUR was significantly
      weaker than MTX (P = 0.006), injectable gold (P less than 0.0001), DP (P less
      than 0.0001), and SSZ (P = 0.009) and was slightly, but not significantly, weaker
      than antimalarial agents (P = 0.11). We also found heterogeneity among
      antimalarial agents, in that patients treated with chloroquine did better than
      those treated with hydroxychloroquine. We found little difference in efficacy
      between MTX, injectable gold, DP, and SSZ. A power analysis showed that a trial
      should contain at least 170 patients per treatment group to successfully
      differentiate between more effective and less effective (e.g., AUR) second-line
      drugs. None of the reported interdrug comparative trials we reviewed were this
      large. For the toxicity study, our inclusion criteria captured RA trials which
      reported the proportion of patients who discontinued therapy because of drug
      toxicity and the total proportion who dropped out. We found 71 clinical trials
      that contained 129 treatment groups. The average proportion who dropped out and
      the average proportion who dropped out because of drug toxicity were computed for
      each drug. Overall, 30.2% of the patients in these trials dropped out; 50% of
      them did so because of drug toxicity. Injectable gold had higher toxicity rates
      (P less than 0.05) and higher total dropout rates (P less than 0.01) than any
      other drug; 30% of gold-treated patients dropped out because of side effects
      versus 15% of all trial patients. Antimalarial drugs and AUR had relatively low
      rates of toxicity; the rate for MTX was imprecise because of discrepancies
      between trials. Thus, of the commonly used second-line drugs, AUR is the weakest,
      and injectable gold is the most toxic. Agents introduced in the future will be
      compared with these drugs.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1977392
TI  - Major histocompatibility complex genes and susceptibility to systemic lupus
      erythematosus.
AB  - Susceptibility to systemic lupus erythematosus is associated with major
      histocompatibility complex (MHC)--encoded genes. We have used nucleotide sequence
      analysis to better define the disease-associated MHC alleles. HLA-DR2, DQw1, and
      especially the rare allele DQ beta 1. AZH confer high relative risk (RR = 14) for
      lupus nephritis in a Caucasian population of patients. Pilot studies using
      historical controls suggest that these genes also confer a high risk in non
      Caucasian ethnic groups (RR = 24-78). We have found that DR4 is significantly
      decreased in patients with lupus nephritis. Fifty percent of the patients with
      lupus nephritis had either the DQ beta 1.1, the DQ beta 1.AZH, or the DQ beta 1.9
      alleles. These alleles share amino acid residues that have been predicted to be
      the contact points for antigen and the T cell receptor. These HLA alleles appear
      to have a direct role in the predisposition to lupus nephritis, whereas DR4 may
      have a "protective" effect.

PMID- 1977393
TI  - General pharmacological profiles of the new beta-adrenoceptor antagonist
      carvedilol.
AB  - General pharmacological properties of carvedilol (BM 14.190) were investigated in
      comparison with propranolol. 1. Central nervous system: Carvedilol caused
      reduction of awareness, motor activity and muscle tone, and staggering gait in
      Irwin's test (mice). It decreased spontaneous motor activity and potentiated
      hexobarbital anesthesia (mice). It lacked anticonvulsant activity (mice) and did
      not have any effect on body temperature (rabbits). Various changes were produced
      in mono- and polysynaptic spinal reflex (cats). In EEG, a slight arousal pattern
      was observed (cats). These effects of carvedilol were weaker than those observed
      after propranolol administration in general. Carvedilol, however, caused
      potentiation of hexobarbital anesthesia at lower doses than propranolol.
      Carvedilol inhibited acetic acid-induced writhing syndrome, whereas it failed to
      show analgesic activity in the tail-pinch test (mice). Propranolol inhibited both
      pain reactions. 2. Respiratory and cardiovascular system (dogs): Carvedilol
      increased respiratory rate and decreased expiratory velocity. It produced
      hypotension and bradycardia. Cardiac contractility was reduced and femoral blood
      flow was transiently increased after carvedilol administration. Propranolol
      induced weaker hypotension and greater bradycardia in comparison with carvedilol.
      It decreased femoral blood flow. 3. Autonomic nervous system: Carvedilol had
      little or no effects on pupil size, whereas propranolol produced mydriasis
      (rabbits). Carvedilol inhibited pressor response to norepinephrine (rats), and it
      also reduced the nictitating membrane contraction induced by pre- and
      postganglionic sympathetic nerve stimulation (cats). Propranolol did not show any
      inhibitory effect on pressor response to norepinephrine and on the contractile
      response induced by preganglionic sympathetic nerve stimulation. 4. Smooth
      muscle: Carvedilol produced inhibitory effects on spontaneous motility, and
      contractile responses to acetylcholine, histamine, nicotine, serotonin and BaCl2
      in isolated ileum (guinea pigs). It also inhibited contractile responses to
      acetylcholine and histamine in isolated trachea (guinea pigs), and spontaneous
      motility in isolated uterus (rats). Carvedilol reduced norepinephrine-induced
      contraction of isolated vas deferens at lower concentration (guinea pigs). 5.
      Digestive system: Decrease in intestinal motility was observed after intravenous
      administration of carvedilol and propranolol (rabbits). However, carvedilol
      failed to influence on gastric motility and tonus, whereas propranolol increased
      them (rabbits). Carvedilol, like propranolol, induced little or no effects on
      gastro-intestinal transit (mice) and gastric emptying rate (rats). Both drugs
      decreased gastric secretion at similar dose (rats). Carvedilol at higher doses
      produced lesion of gastric mucosa, whereas propranolol did not show these effects
      (rats). 6. Skeletal muscle: In in vitro experiment, carvedilol, like propranolol,
      reduced the contractile response of diaphragm to nerve and muscle stimulation
      (rats)...

PMID- 1977394
TI  - Inhibitory effects of azelastine on superoxide anion generation from activated
      inflammatory cells measured by a simple chemiluminescence method.
AB  - Blood was drawn from healthy human volunteers and neutrophils and eosinophils
      were purified on a Conray-Ficoll and a Percoll gradient, respectively. Rat mast
      cells were also purified on a Percoll gradient. Superoxide anion (O2-) generation
      from the cells were measured by 2-methyl-6-[p-methoxy-phenyl]-3,7
      dihydroimidazo[1,2-a]pyrazin+ ++-3-one (MCLA)-dependent luminescence. Addition of
      0.5 mumol/l MCLA and a stimulatory agent, such as phorbol myristate acetate, N
      formyl-methionyl-leucyl-phenylalanine (fMLP) and compound 48/80, to a suspension
      of each cell caused a marked luminescence which was inhibited by 0.5 mumol/l
      superoxide dismutase (SOD). Azelastine (A-5610) significantly inhibited the O2-
      generation from each activated inflammatory cell in a dose-dependent manner. When
      eosinophils were activated by fMLP in the presence of cytochalasine (CB),
      azelastine abolished the luminescence stronger than that from the fMLP-stimulated
      cells in the absence of CB.

PMID- 1977395
TI  - Mechanism of atrial natriuretic polypeptide and sodium nitroprusside-induced
      relaxation in guinea-pig tracheal smooth muscle.
AB  - Atrial natriuretic polypeptide (ANP) is composed of a family of peptides isolated
      from rat and human atria. In the present study, the relaxant effects of ANP,
      sodium nitroprusside and 8-bromo-cyclic guanosine monophosphate (GMP) were
      investigated in guinea-pig tracheal smooth muscle, and the tissue cyclic GMP and
      cyclic adenosine monophosphate (AMP) concentrations were measured. ANP, sodium
      nitroprusside and 8-bromo-cyclic GMP showed relaxant effects on the spontaneous
      tone in normal Krebs solution (5.9 mmol/l K(+)-2.4 mmol/l Ca++ solution). They
      diminished relaxant effects on 40 mmol/l K(+)-0.1 mmol/l Ca++ induced
      contraction, which was approximately the same tension as the spontaneous tone.
      Sodium nitroprusside and 8-bromo-cyclic GMP diminished less relaxant effects on
      40 mmol/l K(+)-2.4 mmol/l Ca++ induced contraction, but ANP showed no relaxation.
      The tissue cyclic GMP levels following administration of ANP and sodium
      nitroprusside in normal Krebs solution, in 40 mmol/l K(+)-2.4 mmol/l Ca++
      solution, and in 40 mmol/l K(+)-0.1 mmol/l Ca++ solution increased dose
      dependently without regard to external Ca++ concentrations, while the tissue
      cyclic AMP levels did not change. These results suggest that ANP might be a novel
      potent relaxant in airway smooth muscle and the relaxant effect may be, at least
      in part, mediated by cyclic GMP. There was a difference in relaxant effects on
      tracheal smooth muscle between ANP and sodium nitroprusside.

PMID- 1977396
TI  - High-pressure liquid chromatographic evaluation of cyclic paracetamol
      acetylsalicylate and its active metabolites with results of a comparative
      pharmacokinetic investigation in the rat.
AB  - Like benorilate, its correlated open ester, MR 897, a cyclic ester between
      acetylsalicylic acid and paracetamol, gives rise to acetylsalicylic acid,
      salicylic acid and paracetamol by enzymatic hydrolysis. An analytical method was
      developed, which detects parent drugs and active metabolites, in order to compare
      the pharmacokinetic and metabolic behaviour of the two products. The method was
      specifically validated for quantitative analysis of salicylic acid and
      paracetamol, which are the main systemic metabolites of both MR 897 and
      benorilate. Extraction from plasma or tissue homogenate was carried out in two
      steps with diethyl ether and acetate. Recovery of the analytical substances
      ranged from 82.7% for paracetamol to 98.5% for salicylic acid. The results of a
      comparative pharmacokinetic investigation of MR 897 and benorilate in the rat
      confirm higher bioavailability and a more favourable plasma level profile with MR
      897.

PMID- 1977397
TI  - Effect of three non-ionic contrast media on rats and rabbits with regard to renal
      changes. Interspecies comparison.
AB  - The effect of three non-ionic contrast media (iosimide, iopamidol and iopromide)
      was investigated in rabbits and rats after single i.v. application up to high
      doses with regard to renal changes. Determinations of serum urea nitrogen and
      creatinine and urinary enzymes (lactate dehydrogenase, gamma-glutamyl
      transpeptidase and N-acetyl-beta-D-glucosaminidase) as well as histological
      examinations of the kidneys were performed. The results obtained demonstrate that
      rabbit as an experimental animal was more sensitive than rat in exhibiting renal
      changes to contrast media. Furthermore, determinations of urinary enzymes
      demonstrated that gamma-GT in rabbits and LDH in rats were the most sensitive
      indicators for detection of early kidney damage. With regard to the high dose
      levels required, these kidney changes do not indicate any risk to humans at
      diagnostic dose levels.

PMID- 1977398
TI  - Laboratory tests in the follow-up of treated alcoholics: how often should testing
      be repeated?
AB  - The study group consisted of 60 male and 13 female alcohol-dependent employed
      patients who participated in inpatient treatment for alcoholism. They were
      followed up bimonthly for eight months after the treatment period. The results
      with GGT, ASAT, ALAT, MCV and the combination of GGT and MCV were studied with
      respect to the effect of taking the tests once (at eight months), twice (once
      every four months) or four times (bimonthly). According to our definition, the
      treatment outcome was good when the laboratory test values were within the normal
      range during the whole follow-up period. The differences in observed outcome (at
      eight months after treatment) were small whether one took the tests once at the
      end of the follow-up period or up to four (i.e. bimonthly) times. Nevertheless,
      there were some differences between the laboratory markers. To get the most
      accurate picture of drinking during the follow-up period one should repeat the
      test bimonthly with ASAT or ALAT, once every four months with GGT (or combined
      GGT and MCV), and once after eight months with MCV. When the time course of
      relapses is important for the study the more frequent test taking is also
      indicated.

PMID- 1977399
TI  - Serum and urinary beta-hexosaminidase as markers of heavy drinking.
AB  - Serum and urinary beta-hexosaminidase (SHEX and UHEX) were determined in 32
      alcoholic men admitted to inpatient detoxification treatment for seven days, and
      in 27 teetotallers. On the admission SHEX was increased in 68.8% and UHEX in
      81.3% and after seven days of abstinence the corresponding percentages were 37.5
      (SHEX) and 71.9 (UHEX). During the treatment SHEX decreased significantly while
      UHEX did not. On the admission to the treatment UHEX correlated positively with
      SHEX (r = 0.54; P less than 0.01). The results suggest that UHEX may be a more
      sensitive marker of heavy drinking than SHEX. Furthermore UHEX stays longer
      elevated than SHEX.

PMID- 1977400
TI  - Prospective evaluation of gastric emptying in the self-poisoned patient.
AB  - The authors prospectively studied the effect of gastric emptying (GE) and
      activated charcoal (AC) upon clinical outcome in acutely self-poisoned patients.
      Presumed overdose patients (n = 808) were treated using an alternate day protocol
      based on a 10-question cognitive function examination and presenting vital sign
      parameters. Asymptomatic patients (n = 451) did not receive GE. AC was
      administered to asymptomatic patients only on even days. GE in the remaining
      symptomatic patients (n = 357) was performed only on even days. On emptying days,
      alert patients had ipecac-induced emesis while obtunded patients received gastric
      lavage. AC therapy followed gastric emptying. On nonemptying days, symptomatic
      patients were treated only with AC. No clinical deterioration occurred in the
      asymptomatic patients treated without GE. AC use did not alter outcome measures
      in asymptomatic patients. GE procedures in symptomatic patients did not
      significantly alter the length of stay in the emergency department, mean length
      of time intubated, or mean length of stay in the intensive care unit. Gastric
      lavage was associated with a higher prevalence of medical intensive care unit
      admissions (P = .0001) and aspiration pneumonia (P = .0001). The data support the
      management of selected acute overdose patients without GE and fail to show a
      benefit from AC in asymptomatic overdose patients.

PMID- 1977401
TI  - [The management of the pregnant patient with psychiatric problems].

PMID- 1977402
TI  - Synthesis and pharmacological evaluation of perhydropyrrolo [3,4-c]pyridine
      derivatives.
AB  - Several N,N'-bis-alkyl-perhydropyrrolo[3,4-c]pyridines 4 and the corresponding
      bis-quaternary derivatives 5 have been prepared through standard methods starting
      from the bicyclic dilactam 2. Compounds 4 and 5 were evaluated for their
      inhibitory properties against acetylcholine (ACh), 1,1-dimethylphenyl
      piperazinium iodide (DMPP), 5-hydroxytryptamine (5-HT) and histamine (H1), and
      the guinea pig isolated ileum. Pharmacological data indicated that the strongest
      anticholinergic activity was shown by the dibenzyl amine 4 g, which among the
      tested molecules presented also a rather potent effect at the ganglia level,
      resulting about three times more potent than hexamethonium as ganglionic blocking
      agent. The preliminary SAR coming from the analysis of the pharmacological
      results are presented and discussed.

PMID- 1977403
TI  - Increased incidence of certain TCR and HLA genes associated with myasthenia
      gravis in Italians.
AB  - In order to study the immunogenetics of myasthenia gravis (MG), we analysed the
      TCR and HLA-class II genes from Italian and Californian myasthenic patients. We
      investigated polymorphisms of the TCR using the full length cDNA probes pGA5 and
      the pT10 for the alpha and beta chains, respectively. The 6.3 kb and 2.0 kb
      polymorphic markers, revealed by the PssI enzyme and the alpha chain probe, were
      shown to be significantly associated with MG. Italian MG patients were HLA typed,
      and allele frequencies showed a significant association of DR3 and DQw2 with MG.
      The relative risk calculated for DR3 was 7.4. T-cell proliferative responses to
      peptides of the AchR alpha chain were also studied and no associations with TCR
      RFLP analysis or HLA-class II typing were observed.

PMID- 1977404
TI  - In vivo activity of an islet-reactive T-cell clone.
AB  - BDC-6.9 is a CD4-positive T-cell clone, specific for NOD islets, which was
      isolated from the spleen and lymph nodes of a diabetic NOD mouse. The cells were
      transplanted in a blood clot adjacent to established NOD islet grafts in diabetic
      (CBA X NOD)F1 recipients. The BDC-6.9 cells initiated extensive damage to the
      islet grafts, while a non-islet specific clone transplanted adjacent to grafted
      islets caused no noticeable damage. In addition, the BDC-6.9 cells initiated
      similar destruction when injected intraperitoneally, suggesting that they may
      have some migratory capacity. By introducing these islet-reactive cells into the
      (CBA X NOD)F1, a non-diabetes prone environment, we hope to clarify the role of
      the islet-specific CD4 cell as related to islet destruction in vivo.

PMID- 1977405
TI  - The function of the invariant chain in antigen presentation by MHC class II
      molecules.
AB  - The existence of different pathways of antigen presentation by class I and class
      II molecules raises two fundamental questions. (1) Why are class II, but not
      class I molecules, transported to the endosomal compartment where the exogenous
      antigen is met? (2) What are the mechanisms that prevent class II molecules from
      being occupied and blocked by endogenous peptides before they reach endosomes?
      These and other questions were discussed at the recent 7th International HLA/H-2
      Workshop. In round table discussions particular attention was paid to the class
      II-associated invariant chain, because it was considered that this molecule was a
      likely candidate to explain some of the differences of class I and class II
      molecules in antigen presentation.

PMID- 1977406
TI  - New concepts in immunodeficiency diseases.
AB  - The study of primary immunodeficiencies has, in the past, contributed greatly to
      knowledge of the intact immune system. More recently this process has been
      reversed, resulting in an explosion of new information on the nature of primary
      immune defects. In this summary of the Jeffrey Modell Symposium, Sudhir Gupta
      gives a syndrome-by-syndrome account of the latest developments.

PMID- 1977407
TI  - Interactions between immune activation cascades and biosynthesis of
      neurotransmitters.

PMID- 1977408
TI  - Behavioural and neurochemical effects of Ro 40-7592, a new COMT inhibitor with a
      potential therapeutic activity in Parkinson's disease.
AB  - Behavioural and some neurochemical effects of Ro 40-7592 (3,4-dihydroxy-4'-methyl
      5-nitrobenzophenone), a new COMT inhibitor, were studied in rats and mice. Ro 40
      7592 increased the effect of L-DOPA (plus benserazide) on locomotor activity,
      reserpine-induced hypothermia, and catalepsy induced by pimozide, haloperidol and
      fluphenazine. Locomotor hyperactivity induced by amphetamine or nomifensine, as
      well as stereotypy induced by amphetamine (but not apomorphine), were also
      increased by Ro 40-7592. The drug stimulated exploratory activity in the open
      field test. It decreased the levels of HVA and 3-MT, increased the level of DOPAC
      but did not change the levels of dopamine in the striatum, nucleus accumbens and
      frontal cortex. These results indicate that Ro 40-7592 may improve the therapy
      with L-DOPA (plus decarboxylase inhibitor) of Parkinson's disease.

PMID- 1977409
TI  - Neuroleptic-induced catalepsy as a model of Parkinson's disease. I. Effect of
      dopaminergic agents.
AB  - Catalepsy was observed in the rat following intrastriatal injections of the
      dopamine antagonists sulpiride or fluphenazine and after subcutaneous
      administration of fluphenazine. The neuroleptic-induced catalepsy was reversed by
      the classical anti-parkinsonian agent L-DOPA and by agents that function through
      dopamine systems such as d- and methamphetamine and the direct D2 receptor
      agonist quinpirole. The D1 agonist SKF 38393, and the D1/D2 agonist apomorphine,
      were ineffective in this model. These results support limited use of the rat
      catalepsy model for the screening of potential anti-parkinsonian compounds and
      indicate that this procedure can provide valuable information concerning striatal
      dopamine function.

PMID- 1977410
TI  - Neuroleptic-induced catalepsy as a model of Parkinson's disease. II. Effect of
      glutamate antagonists.
AB  - Subcutaneous administration of fluphenazine elicits catelepsy that can be
      attenuated by the glutamate antagonists MK801 and phencyclidine (PCP). 3-[-(+)-2
      carboxy piperazine-4-yl]-propyl-1-phosphanate (CPP) was found to be ineffective
      in this model. Intrastriatal injections of sulpiride or fluphenazine were also
      found to induce catalepsy which could be attenuated by MK801 and PCP. These
      results illustrate that nondopaminergic compounds might possibly be of value in
      the treatment of Parkinson's disease. Furthermore it was demonstrated that this
      paradigm can be utilized to investigate neurotransmitter interactions within the
      striatum. This was clearly emphasized by the observation that bilateral
      administration of MK801 into the striatum increased basal locomotor activity.

PMID- 1977411
TI  - [Effect of naloxone on basal, by somatostatin inhibited stomach secretion in
      patients with chronic duodenal ulcer].
AB  - In 13 men with chronic duodenal ulcer disease effects of somatostatin and
      naloxone on basic gastric secretion were determined. Following intravenous
      somatostatin infusion a significant increase in basic gastric secretion was
      observed. Somatostatin also induced a significant increase in sodium
      concentration and a decrease in chloride concentration in the gastric juice.
      Total electrolyte and mucoprotein secretions changed proportionally to
      alterations in the gastric juice volume. Somatostatin-induced gastric secretion
      was unaffected by a single intravenous naloxone administration. In patients with
      chronic duodenal ulcer disease somatostatin and naloxone affect gastric secretion
      independently of each other.

PMID- 1977412
TI  - NMDA agonists and antagonists alter the hypnotic response to ethanol in LS and SS
      mice.
AB  - Involvement of glutamate neurotransmission in the differential response of long
      sleep (LS) and short-sleep (SS) mice to acute ethanol was examined by measuring
      the effect of centrally administered glutamate receptor agonists and antagonists
      on blood ethanol concentration (BEC) at loss of righting response following
      intragastric administration of ethanol. NMDA coinjected with glycine, and
      quinolinic acid (QA), decreased sensitivity to ethanol in both lines of mice. SS
      mice were more sensitive to QA than were LS. The NMDA antagonists 2-amino-5
      phosphonovaleric acid (APV), MK-801 and an inhibitor of glutamate synthesis,
      methionine sulfoximine, increased sensitivity to ethanol in both lines of mice.
      MK-801 effects were line dependent with SS being more sensitive. In addition,
      coinjection of APV, Mg++ or Zn++ with QA blocked the decrease in sensitivity seen
      with QA alone. These results demonstrate that NMDA agonists and antagonists alter
      the acute hypnotic response to ethanol in both LS and SS mice, and support the
      hypothesis that ethanol exerts its effects in part by altering glutamatergic
      neurotransmission.

PMID- 1977413
TI  - Cerebral abscess.

PMID- 1977415
TI  - International seminar on calcium metabolism in hypertension. September 1988,
      Tokyo. Proceedings.

PMID- 1977414
TI  - Nerve cell clusters in dorsal striatum and nucleus accumbens of the male rat
      demonstrated by glucocorticoid receptor immunoreactivity.
AB  - Glucocorticoid receptor-immunoreactive nerve cells have been analysed in the
      dorsal striatum and nucleus accumbens of the rat by means of a monoclonal
      antibody against rat liver glucocorticoid receptor. Glucocorticoid receptor
      immunoreactivity was present in the nuclei of the vast majority of the striatal
      nerve cells. The analysis of sections stained with glucocorticoid receptor
      antibody and cresyl violet showed that around 90% of the entire striatal neuronal
      population contained glucocorticoid receptor immunoreactivity. By means of the
      double immunoperoxidase technique evidence was provided that somatostatin- and
      choline acetyltransferase-immunoreactive nerve cells in the striatum do not
      contain glucocorticoid receptor immunoreactivity. The density of glucocorticoid
      receptor-immunoreactive nerve cells in the grey matter and the presence of
      clusters of glucocorticoid receptor-immunoreactive nerve cells have been
      investigated in three fields located in the medial and central dorsal striatum
      and nucleus accumbens at the coronal level A 8620 microns according to the Konig
      and Klippel atlas using computer-assisted image analysis. Every aggregate
      containing three or more glucocorticoid receptor-immunoreactive nerve cells,
      which had an intercenter distance less than the mean diameter (10-11 microns) of
      the striatal cells, was considered an island. A higher density of both
      glucocorticoid receptor-immunoreactive nerve cell nuclei and islands was found in
      the nucleus accumbens with respect to dorsal striatal areas. The most frequent
      island formed consisted of three to ten nerve cells both in dorsal striatum and
      nucleus accumbens. Furthermore, some nucleus accumbens islands contained up to
      100 nerve cells, whereas in the dorsal striatum the maximum number of
      glucocorticoid receptor-immunoreactive nerve cells per island ranged from 50 to
      60. The present procedure proved to be a sensitive method to reveal clusters of
      chemically identified structures and provided evidence for a basic
      cytoarchitectonic organization of the dorsal striatum and nucleus accumbens of
      the rat. This paper also demonstrated that the vast majority, but not all,
      striatal nerve cells contained glucocorticoid receptor immunoreactivity, and thus
      may be under the control of circulating glucocorticoids. In fact, only small
      transmitter-identified neuronal populations, such as somatostatin- and choline
      acetyltransferase-immunoreactive nerve cells, were devoid of glucocorticoid
      receptor immunoreactivity.

PMID- 1977416
TI  - Effects of light and an alpha-2-adrenergic agonist on serotonin N
      acetyltransferase activity in chick pineal gland.
AB  - Pineal serotonin N-acetyltransferase (NAT) is the enzyme that catalyzes the
      production of N-acetylserotonin from serotonin and is the rate limiting step in
      the biosynthesis of melatonin in the chick pineal gland. Chick pineal NAT
      activity is decreased by light and by noradrenergic agents that act at the alpha
      2-adrenergic receptor. Light-induced inhibition of nocturnal NAT activity can be
      demonstrated by exposing 4-day-old chicks to light, or by exposing pineal gland
      explants cultured in vitro either to light or to UK 14,304 (an alpha-2-adrenergic
      agonist). The inhibition by either light or UK 14,304 is preceded by a transient,
      but consistent rise in NAT activity. The paradoxical, transient light-induced
      rise in enzyme activity is mimicked by UK 14,304 which suggests a similarity in
      mechanisms of light and adrenergic signal transduction associated with the
      regulation of NAT activity.

PMID- 1977417
TI  - Autoradiographic analysis of regional alterations in brain receptors following
      chronic administration and withdrawal of typical and atypical neuroleptics in
      rats.
AB  - Rats were administered haloperidol, clozapine, raclopride, or no drug for 28 days
      or 8 months. Following a 3 week withdrawal period, in vitro autoradiography was
      utilized to examine receptor binding for dopamine D2 ([3H]spiperone and
      [3H]raclopride), dopamine D 1 ([3H]SCH23390), GABA(A) ([3H]muscimol),
      benzodiazepine ([3H]RO15-1788), and muscarinic ACh receptors ([3H]QNB).
      [3H]spiperone was elevated in striatal subregions only in haloperidol-treated
      rats, with the largest increases seen in the 8 month duration animals. Striatal
      [3H]raclopride binding was increased after both short- and long-term treatment in
      both haloperidol and raclopride, but not clozapine-treated animals. Clozapine
      treated rats showed significant increases in [3H]SCH23390 in the nucleus
      accumbens after 28-day administration; otherwise no changes were seen for this
      ligand in any other groups. Increases in [3H]muscimol binding in the substantia
      nigra reticulata were seen in haloperidol-treated rats after 8 month treatment.
      Binding of [3H]QNB and [3H]RO151788 were not significantly different from control
      for any of the drug-treated groups. These data suggest that persisting
      alterations in receptor binding are primarily seen in dopamine D2 and GABA
      receptors after withdrawal from chronic administration of haloperidol but not the
      atypical neuroleptics, clozapine and raclopride.

PMID- 1977418
TI  - Characterization of an insect ferritin subunit synthesized in a cell-free system.
AB  - Ferritin, an iron-sequestering and -binding protein, is localized to the vacuolar
      system in Calpodes ethlius larvae. The amount of iron-loaded ferritin in intact
      larval midgut can be increased by pretreatment with iron. When poly(A)+ RNA from
      control or iron-treated larvae was translated in vitro, a 24 kilodalton (kDa)
      protein was a major translation product. If the cell-free system was supplemented
      with dog pancreatic microsomes, the 24-kDa protein was not detectable: the major
      translation product was 28-30 kDa. The 24-kDa and 28- to 30-kDa proteins were
      identified as ferritin subunits by immunoprecipitation with anti-Manduca ferritin
      antibodies. Proteinase K digestion of the translation products showed that the 28
      to 30-kDa subunit was targeted into the lumen of, and protected by, the
      microsomes. The change in molecular mass of the ferritin monomer was attributed
      to glycosylation of the 24-kDa subunit within the lumen of the microsomes. This
      was demonstrated by (i) the ability of the 28- to 30-kDa subunit, but not the 24
      kDa subunit, to bind concanavalin A on Western blots and (ii) inhibition of the
      change in molecular mass from 24 to 28-30 kDa if tunicamycin is added to the
      microsomes. The results indicate that the Calpodes ferritin subunit was
      synthesized, targeted to microsomes, and glycosylated within their lumen in a
      rabbit reticulocyte cell-free system primed with midgut poly(A)+ RNA extracted
      from control or iron-treated larvae.

PMID- 1977419
TI  - Alzheimer disease and the dementia of Parkinson disease: comparative
      investigations.
AB  - Intellectual abnormalities are common in Parkinson disease (PD), occurring in a
      majority of patients and exhibiting a spectrum of severity from mild to severe.
      Alzheimer disease (AD) has been posited as the cause of dementia in PD.
      Comparative neuropsychological studies, however, show differences in memory,
      language, and frontal lobe functions between AD and PD patients even when the two
      groups have comparably severe dementia syndromes. The AD-type neuropathology
      occurs in 10-60% of PD patients, and dementia is usually overt when AD pathology
      is identified at autopsy. The AD changes are less frequent than intellectual
      deterioration in PD, and dementia has been observed in PD patients without AD
      pathology. Therefore, concurrent AD cannot be the cause of all cases of dementia
      in PD. Cholinergic deficits occur in some PD patients, but cholinergic deficits
      have been described in patients without dementia and dementia has been documented
      in patients without cholinergic system abnormalities. Dopaminergic disturbances
      contribute to the dementia of PD. Differences in neuropeptide concentrations,
      electrophysiologic responses, and cerebral metabolism also support
      pathophysiologic distinctions between AD and the dementia of PD. Genetic
      investigations suggest a role for heredity in AD, whereas PD appears to be an
      acquired, nongenetic disorder. These studies indicate that despite areas of
      overlap in clinical symptoms and neuropathology, AD and the dementia of PD are
      largely distinct.

PMID- 1977420
TI  - Rectal electrogenic secretion--is it a putative indicator of intestinal secretory
      status induced by nutritional deprivation in the rat?
AB  - Intestinal secretion is enhanced by starvation in rats. The rectum from fed and 3
      day-starved rats generates a basal electrogenic ion transfer (short-circuit
      current) in vitro which is mainly electrogenic Na+ absorption (amiloride
      sensitive, 66-71%) with a small component of electrogenic chloride secretion
      (furosemide-sensitive, 14-22%). Bethanechol, a muscarinic agonist, caused an
      increase in the short-circuit current (mainly furosemide-sensitive chloride
      secretion) and potential difference in rectums from both fed and starved rats but
      the respective values for the starved animals were 100% and 64% greater. In
      starvation, the rat rectum is an indicator of intestinal secretory status. The
      result warrants investigation of human rectal electrogenic secretion in
      nutritional deprivation.

PMID- 1977421
TI  - Cloning of a novel glutamate receptor subunit, GluR5: expression in the nervous
      system during development.
AB  - We have isolated cDNAs encoding a glutamate receptor subunit, designated GluR5,
      displaying 40%-41% amino acid identity with the kainate/AMPA receptor subunits
      GluR1, GluR2, GluR3, and GluR4. This level of sequence similarity is
      significantly below the approximately 70% intersubunit identity characteristic of
      kainate/AMPA receptors. The GluR5 protein forms homomeric ion channels in Xenopus
      oocytes that are weakly responsive to L-glutamate. The GluR5 gene is expressed in
      subsets of neurons throughout the developing and adult central and peripheral
      nervous systems. During embryogenesis, GluR5 transcripts are detected in areas of
      neuronal differentiation and synapse formation.

PMID- 1977422
TI  - Potentiation of glutamate-activated currents in isolated hippocampal neurons.
AB  - "Fast chemical stimulation" was shown to induce potentiation of glutamate
      activated currents in neurons isolated from rat hippocampus. A fast application
      system allowed solution changes up to a rate of 20 Hz. In Mg2(+)-free solution,
      the response to glutamate application immediately after repetitive stimulation
      with glutamate plus glycine was increased by 25%-88%, returning to control levels
      over 10-15 min. Enhancement of glutamate-induced currents was also seen after
      stimulation with solutions containing aspartate or NMDA plus glycine. Aspartate
      induced currents were not potentiated. These and other observations demonstrate
      that in a purely "postsynaptic" system, short-term potentiation can be induced
      and is mediated via NMDA receptors whereas the potentiated current is carried via
      non-NMDA glutamate receptor channels.

PMID- 1977423
TI  - Surgical correction of a severely obstructed pulmonary artery bifurcation in
      Takayasu's arteritis.
AB  - A young male patient (NYHA III) presented with a severe pulmonary artery
      bifurcation stenosis of unknown origin. He underwent successful radical resection
      and endarterectomy of abundant endoluminal and perivascular inflammatory tissue.
      Surgery was performed with extracorporeal circulation (ECC) without transection
      of the aorta and the pulmonary artery bifurcation was enlarged with a patch.
      Right ventricular to peripheral pulmonary artery pressure gradient fell from 80
      mmHg preoperatively to 25 mmHg 18 months postoperatively. The patient is fully
      rehabilitated and working (NYHA I). Histological examination confirmed Takayasu's
      arteritis as the underlying disease and medium-term follow-up angiography showed
      an almost normal pulmonary artery bifurcation. We conclude that the radical
      surgical approach is a valuable palliation in this disease.

PMID- 1977424
TI  - Bestatin (Ubenimex)--a low molecular immunomodifier. Papers from a workshop at
      the 16th International Congress of Chemotherapy. Jerusalem, June 11-16, 1989.
      Proceedings.

PMID- 1977425
TI  - [A case of Salmonella subdural empyema (first case in Japan)].

PMID- 1977426
TI  - [The synergistic action of glutamic acid and phosphocreatine on the metabolism
      and function of the heart during ischemia and reperfusion].
AB  - The combined effect of glutamic acid (15 mM) and phosphocreatine (10 mM) on
      metabolism and postischemic recovery of cardiac function was studied in isolated
      perfused working guinea pig hearts. Addition of these two agents into standard
      hyperpotassium cardioplegic solution increased twice the recovery of the aortic
      output and improved restoration of volume work and an index of functional
      recovery. This effect was combined with the complete recovery of ATP,
      phosphocreatine, the decrease in ammonia and lactate tissue contents and
      preservation of amino acid pool. Lesser leakage of creatine and creatine kinase
      pointed to lesser damage of the sarcolemma. The results show the effectiveness of
      the use of cardioplegic solution containing both glutamic acid and
      phosphocreatine.

PMID- 1977427
TI  - Full-length recombinant CD4 and recombinant gp120 inhibit fusion between HIV
      infected macrophages and uninfected CD4-expressing T-lymphoblastoid cells.
AB  - Human immunodeficiency virus-(HIV) infected monocyte-macrophages may contribute
      to the pathogenesis of HIV-associated immune deficiency and dysfunction by acting
      as a target and potential reservoir for the virus in vivo, and by functioning
      abnormally following infection. We have shown that HIV-infected macrophages fuse
      with uninfected CD4-expressing lymphoid cells in vitro; this may provide an
      additional mechanism for CD4 lymphocyte depletion in vivo. We report here the
      inhibition of syncytium formation between HIV-infected macrophages and uninfected
      CD4-expressing T-lymphoid cells by monoclonal antibody S3.5, directed against an
      epitope of CD4 involved in binding HIV gp120, by a recombinant protein that
      comprises the full-length extracellular domain of the CD4 molecule, and by
      recombinant full-length HIV envelope glycoprotein, gp120. These results indicate
      that both molecules (gp120 and CD4) are critical to the fusion process, and
      suggest that gp120 is expressed on the surface of HIV-infected monocyte
      macrophages.

PMID- 1977428
TI  - Papers presented at the Conference on HIV, Lentiviruses, and the Monocyte
      Macrophage. November 9-10, 1989, San Francisco, California. Proceedings.

PMID- 1977429
TI  - Gastroduodenal pathology and Helicobacter pylori. Third workshop of the European
      Helicobacter pylori Study Group. Proceedings.

PMID- 1977430
TI  - Placebo controlled trial of xamoterol versus digoxin in chronic atrial
      fibrillation.
AB  - Thirteen patients in chronic atrial fibrillation with a normal resting heart rate
      but with exercise tachycardia and episodes of bradycardia were randomised to
      treatment periods of two weeks on xamoterol (200 mg twice daily), low dose
      digoxin, or placebo, in a blind crossover study. The results (mean SEM) of
      symptom scores, a treadmill exercise test, and 24 hour ambulatory
      electrocardiographic monitoring were obtained. Xamoterol improved symptom scores
      and controlled exercise heart rate better than digoxin. Xamoterol was better than
      digoxin or placebo in reducing the heart rate response to exercise and tended to
      improve exercise duration. Xamoterol, by reducing the daytime maximum hourly
      heart rate and increasing the night time minimum hourly heart rate, significantly
      reduced the difference between the two compared with placebo. In contrast,
      digoxin tended to reduce both the maximum and minimum hourly heart rates through
      day and night. Both the frequency and duration of ventricular pauses were reduced
      by xamoterol but tended to increase with digoxin. Xamoterol reduced both the
      circadian variation in ventricular response to atrial fibrillation and exercise
      tachycardia by modulating the heart rate according to the prevailing level of
      sympathetic activity. These changes were translated into symptomatic benefit for
      the patients studied.

PMID- 1977431
TI  - Effects of sufentanil on median nerve somatosensory evoked potentials.
AB  - We have studied the effects of a single i.v. dose of sufentanil 5 micrograms kg-1
      in combination with pancuronium on the median nerve short latency somatosensory
      evoked potentials (SSEP) in 15 unpremedicated patients undergoing thoracic or
      lumbar spinal surgery. The latency and amplitude of the SSEP response over the
      second cervical vertebra (SC) and sensory cortex (P17, N20, P25), heart rate and
      arterial pressure were recorded for 30 min after the injection of sufentanil. A
      significant increase in mean latency occurred for N20 (P less than 0.003) and P25
      (P less than 0.002) within 2 min, but the absolute increase in latency was small.
      The mean amplitudes of all peaks decreased to 60% (SC), 70% (P17), 60% (N20) (P
      less than 0.012) and 45% (P25) of the baseline value within 7 min. The results
      suggest that the major change in median nerve SSEP produced by this dose of
      sufentanil is a reduction in amplitude, and that major changes in latency after
      sufentanil and pancuronium are probably caused by other influences.

PMID- 1977432
TI  - Cardiovascular and renal haemodynamic effects of dopexamine: comparison with
      dopamine.
AB  - We have studied the effects of dopexamine and dopamine on systemic and renal
      haemodynamics in 20 male patients undergoing elective coronary artery bypass
      surgery. Patients were allocated randomly to two groups (n = 10) who were treated
      with incremental doses of either dopexamine 1, 2 and 4 micrograms kg-1 min-1, or
      dopamine 2.5 and 5 micrograms kg-1 min-1, each dose being maintained for 15 min.
      Measurements were performed before administration of the drug and at the end of
      the infusion period at each dose. Fentanyl and midazolam were used as anaesthetic
      agents. Renal blood flow was measured with the argon washin technique. Dopexamine
      4 micrograms kg-1 min-1 produced an increase in cardiac index of 117% caused by a
      65% reduction in afterload and an increase in heart rate by 61%. Dopamine 5
      micrograms kg-1 min-1 caused a 40% increase in cardiac index as a result of an
      increase in stroke volume. Renal vascular resistance decreased more than systemic
      vascular resistance with dopamine. With dopexamine, the increase in renal blood
      flow (66%) was less than the increase in cardiac index, while renal vascular
      resistance and systemic vascular resistance declined to almost the same extent.
      The results show that dopexamine exerts systemic and renal effects mainly via
      stimulation of beta 2-receptors. An action of dopexamine at renal DA1-receptors
      could not be demonstrated in this study.

PMID- 1977433
TI  - Redistribution of cardiac output caused by opening of arteriovenous anastomoses
      by a combination of azaperone and metomidate.
AB  - The effects of the butyrophenone, azaperone 5 mg kg-1 i.m. alone and after
      addition of the imidazole derivative metomidate 6 mg kg-1 i.v. were studied in
      eight conscious pigs. Fifteen minutes after administration of azaperone, systemic
      arterial pressure was reduced by 35% as a result of a 45% increase in systemic
      vascular conductance and 10% decrease in cardiac output (Q). After azaperone, 23%
      of the radioactive labelled microspheres (15 (SD 1) microns) injected into the
      left atrium were detected in the lungs as a result of opening of arteriovenous
      anastomoses (baseline 3%). The increase in arteriovenous anastomotic blood flow
      was at the expense of the nutritional (= capillary) channels. Flow to the brain
      was maintained, but that to the left ventricle decreased in parallel with the
      reduction in arterial pressure. Vascular conductance of most other organs, except
      the skin, increased or was maintained. The addition of metomidate had no effect
      on Q because an increase in stroke volume (by 30%) compensated for the decrease
      in heart rate. Systemic vascular conductance decreased, most noticeably in the
      brain, left ventricle and skeletal muscle. We conclude that azaperone alone and
      in combination with metomidate had only a moderate effect on Q, but caused a
      redistribution in favour of arteriovenous anastomoses.

PMID- 1977434
TI  - Immunological aspects of virus-associated human tumors.

PMID- 1977435
TI  - Toward the function of Ras: filling in the GAPs.

PMID- 1977436
TI  - Plant alkaloids.

PMID- 1977437
TI  - Multidrug resistance.

PMID- 1977439
TI  - Cancer imaging with radiolabeled antibodies.

PMID- 1977438
TI  - Pharmacodynamic without pharmacokinetic interaction between cicloprolol, a
      partial beta 1-adrenoceptor agonist, and digoxin in healthy subjects.
AB  - 1. Cicloprolol is a partial beta 1-adrenoceptor agonist considered for the
      treatment of patients with coronary artery disease and impaired left ventricular
      function. In such patients, digoxin remains in widespread use. 2. We assessed the
      pharmacokinetic and pharmacodynamic interaction between oral cicloprolol 50 mg
      day-1 and oral digoxin 0.25 mg day-1 in 10 healthy male volunteers, using a
      double-blind, randomised protocol, during three 8 day periods. Digoxin was given
      alone during the first period to reach steady state; then digoxin was given with
      cicloprolol or placebo during the second and third periods, according to a cross
      over design. 3. No significant adverse effects were observed. 4. The
      pharmacokinetics of digoxin were not different significantly at the end of the
      placebo-digoxin and cicloprolol-digoxin periods. 5. A significant increase in
      minimum heart rate and mean nocturnal heart rate, assessed by 24 h Holter
      recordings, was observed at the end of the cicloprolol-digoxin period as compared
      with the placebo-digoxin period (means +/- s.e. mean, 57.1 +/- 3.2 beats min-1 vs
      52.2 +/- 3.1 beats min-1, P less than 0.01; and 65.6 +/- 3.8 beats min-1 vs 59.9
      +/- 3.9 beats min-1, P less than 0.01, respectively). 6. A significant increase
      in left ventricular ejection fraction and shortening fraction, assessed by
      echocardiography, was noted at the end of the cicloprolol-digoxin period as
      compared with the placebo-digoxin period (means +/- s.e. mean, 66.4 +/- 1.4% vs
      61.3 +/- 1.2%, P less than 0.05; and 37.0 +/- 1.1% vs 33.3 +/- 0.9%, P less than
      0.05, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1977440
TI  - Antibody targeting: theoretical considerations.

PMID- 1977441
TI  - Intraperitoneal delivery of monoclonal antibodies.

PMID- 1977442
TI  - Chelates and antibodies: current methods and new directions.

PMID- 1977443
TI  - Radiolabeling antibodies via the cyclic anhydride of DTPA--experiences of 5
      years.

PMID- 1977444
TI  - Bifunctional chelating agents for radiometal-labeled monoclonal antibodies.

PMID- 1977445
TI  - Optimization of biodistribution by introducing different chemical linkages
      between antibody and an indium-111 chelate.

PMID- 1977446
TI  - Novel bifunctional linkers for antibody chelation with radiometals.

PMID- 1977447
TI  - Labeling of anti-tumor antibodies and antibody fragments with Tc-99m.

PMID- 1977448
TI  - Requirements for the use of radioimmunodetection of cancer in clinical practice.

PMID- 1977449
TI  - In-vivo antibody imaging for the detection of human tumors.

PMID- 1977450
TI  - Experimental model systems for antibody targeting and radioimmunodetection.

PMID- 1977451
TI  - In-111 monoclonal antibody immunoscintigraphy of colorectal cancer.

PMID- 1977452
TI  - Clinical radioimmunodetection: the second decade.

PMID- 1977453
TI  - Tumor targeting with monoclonal antibody B72.3: experimental and clinical
      results.

PMID- 1977454
TI  - Antibody imaging of endocrine tumors.

PMID- 1977455
TI  - Diversity of the human immune response to clinically used murine monoclonal
      antibodies.

PMID- 1977456
TI  - Antibody lymphoscintigraphy.

PMID- 1977457
TI  - Radioimmunoguided surgery: a new intraoperative approach to the detection of
      tumor.

PMID- 1977458
TI  - Augmentation of tumor antigen expression by recombinant human interferons:
      enhanced targeting of monoclonal antibodies to carcinomas.
AB  - The use of Mabs for the detection and treatment of human carcinoma lesions can
      still be regarded in its infancy. As with other new approaches to cancer therapy,
      several conceptual as well as real problems exist when designing clinical
      protocols for Mab-directed immunotherapy. From the Mab standpoint, studies using
      the intact IgG have shown that, in a majority of patients injected with IgG,
      human anti-mouse IgG antibodies develop that hamper the effectiveness of
      subsequent antibody administration. It is believed that the human anti-mouse
      antibody response is directed against the Fc region of the IgG molecule. The
      elimination of this region through fractionation of the Mab to obtain the minimum
      binding site could result in a less immunogenic molecule. Another approach aimed
      at reducing the immunogenicity of the Mab would be to clone the genes encoding
      for individual Mabs, reduce them via restriction endonuclease techniques, and
      insert human immunoglobulin constant regions. The resulting chimeric antibodies
      are believed to reduce the development of human anti-mouse antibodies. Effective
      Mab therapy of human tumor lesions may also be achieved through the recruitment
      of a portion of the host's immunologic defense system. An example is the use of
      anti-idiotype Mabs that use as immunogen a Mab to a tumor antigen. The anti
      idiotype antibodies are selected for binding to the antigen binding, or idiotype,
      region of the first Mab. The binding sites of the new anti-idiotype Mabs should
      reflect the 'internal image' of the original antigen. The anti-idiotype
      antibodies may be used to immunize patients (i.e., vaccines) in an attempt to
      mount an active immune response against the antigen-positive tumor cells. Recent
      studies have shown a synergism between interferon-alpha and an anti-idiotype Mab
      for the in-vivo antitumor activity in a murine B-cell lymphoma experimental
      model. Whether an interferon-mediated increase in the tumor antigen or the Fc
      receptor was part of the synergism was not investigated. Mabs alone have also
      been shown to elicit cytotoxic activity in vitro and tumoricidal activity in
      vivo. Antibodies of the IgG2a isotype can direct macrophage-mediated
      cytotoxicity. These studies revealed the importance of the number of antibody
      sites per cell as well as the number of cells that bind the IgG2a Mab, thus
      suggesting a 'threshold' requirement for the demonstration of effective tumor
      cell lysis in vitro and in vivo.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1977459
TI  - Anti-antibody enhancement of tumor imaging.

PMID- 1977460
TI  - Preclinical models and methods for the study of radiolabeled monoclonal
      antibodies in cancer diagnosis and therapy.

PMID- 1977461
TI  - Physiology of monoclonal antibody accretion by tumors.
AB  - During the past 8 years numerous patients have been injected with radiolabeled
      monoclonal antibodies for both the diagnosis and treatment of cancer. In general
      the results, while somewhat promising, have failed to fulfill initial
      expectations. It is now clear that there are many physiologic barriers that
      antibodies face in their trek toward their tumor-binding site. Use of terms such
      as antibody-guided delivery or antibody-guided targeting do not take into account
      the fact that the antibodies are subject to the same physiologic rules as drugs
      and hormones. Antibodies are no more 'guided' than any drug or hormone. They
      reach their binding site via the same delivery mechanisms and accumulate in
      proportion to their 'receptor's' (antigen's) density. Our knowledge and
      understanding of the physiologic barriers to the uptake of tumor-associated
      monoclonal antibodies is limited. To date very few studies have been reported
      that shed light on this problem. For radiolabeled monoclonal antibodies to
      fulfill their promise, a greater understanding of these physiologic barriers is
      needed in order to devise ways in which they may be overcome.

PMID- 1977462
TI  - Polyarteritis nodosa, Churg-Strauss syndrome, and other eosinophilic syndromes.

PMID- 1977463
TI  - [1st National Congress of the Italian Association of Visceral Anastomosis.
      Ischia, May 28-30, 1989. Proceedings].

PMID- 1977464
TI  - A comparative study of terfenadine at two dose levels in the management of
      hayfever.
AB  - One hundred and twenty patients with hayfever were enrolled in a single-centre,
      double-blind crossover study designed to compare the efficacy and safety of
      terfenadine at doses of 60 mg bd and 120 mg bd. A two-week placebo run-in period
      was followed by the two treatment periods, each lasting two weeks. Assessments of
      hayfever symptoms were made daily by patients and at each clinic visit by the
      investigator. Adverse events were recorded at the end of each treatment period.
      At the end of the study both investigator and patient rated the overall efficacy
      and the patient recorded treatment preference. The data were examined by analysis
      of variance (ANOVA) for treatment, period and crossover effects. Pollen counts
      were recorded for the duration of the study. Seventy-four patients completed the
      study, the majority of withdrawals occurring during the placebo phase. There was
      no significant difference in symptom relief between the two doses of terfenadine.
      The number of adverse events, including drowsiness, was similar for the two
      treatments and for placebo. Mean and peak pollen counts both correlated well with
      symptom severity. These data show that terfenadine 60 mg bd is an adequate dose
      for the treatment of hayfever symptoms.

PMID- 1977465
TI  - The degree of genetic disparity between donor and host correlates with survival
      of intraventricular substantia nigra grafts.
AB  - We have evaluated the degree of genetic disparity that permits survival of
      intraventricular brain tissue grafts without additional immunosuppression. Fisher
      344 rats (n = 100) with unilateral substantia nigra lesions were used as hosts.
      Donors consisted of Fischer 344 rats (isografts), Sprague-Dawley rats
      (allografts), mice, hamsters, and rabbits (xenografts). Grafts were obtained from
      the ventral mesencephalon of embryonic animals. The functional properties of the
      grafts were measured by behavioral rotation tests. Frequency of graft survival
      determined histologically was related to the degree of genetic disparity between
      donor and host. In comparing rabbit and hamster xenografts, the greater degree of
      disparity for the rabbit-to-rat grafts was associated with a shorter period of
      behavioral recovery (3 weeks vs. 5 to 6 weeks) after transplantation. It is
      concluded that rejection of intracerebral brain tissue grafts does not occur as
      an all-or-none process, but instead varies as a function of the degree of genetic
      disparity between donor and host.

PMID- 1977466
TI  - Amplification and protein over-expression of the neu/HER-2/c-erbB-2 protooncogene
      in human breast carcinomas: relationship to loss of gene sequences on chromosome
      17, family history and prognosis.
AB  - c-erbB-2 gene amplification and protein over-expression were investigated in 89
      primary tumours and 24 metastases from Norwegian breast cancer patients.
      Amplification occurred in 22.5% of the primary tumours and 50% of the metastases.
      The amplification was negatively correlated to the oestrogen receptor (ER)
      content in both the primary tumours and the metastases. No significant
      differences between amplified and non-amplified tumours were observed with regard
      to node status, clinical stage, tumour size or menopausal status, although
      correlations of borderline significance were found between node status, clinical
      stage and high degree of gene amplification. All the amplified tumours were of
      the invasive ductal type. Follow-up data of patients observed for more than 1
      year showed a significantly higher recurrence rate in the c-erbB-2 amplified
      group. Allele loss of chromosome 17p and of 7q was seen in 55% and 48% of the
      tumours respectively. No significant correlation was found between these losses
      and clinico-histological parameters. More than 50% of the tumours with a loss of
      17q sequences had an amplification of c-erbB-2 which is located on 17q12-21,
      indicating that only one of the chromosomes may be involved in the amplification
      of the c-erbB-2. A trend towards a correlation between loss of 17q and high
      degree of amplification were found. No correlation was found between positive
      family history of breast cancer and c-erbB-2 gene amplification, nor loss of 17p
      or 17q sequences. Our data support the hypothesis that amplification correlates
      with aggressive tumour behaviour, and thus may be used as a prognostic factor in
      breast carcinomas. The allele losses on 17p and 17q points to tumour suppressor
      gene or genes on this chromosome, although not as predisposing genes in families.

PMID- 1977467
TI  - The effect of in utero ethinyl oestradiol exposure on the risk of cryptorchid
      testis and testicular teratoma in mice.
AB  - Epidemiological findings indicate that both cryptorchid testis and testicular
      germ cell cancer may be a result of high maternal oestrogen levels early in
      pregnancy. An experiment was conducted with a mouse strain (129 Sv-S1 C P) in
      which the males are susceptible to testicular teratomas to determine if the
      frequency of undescended testis and testicular teratoma in male offspring could
      be increased by administration of ethinyl oestradiol (EE) to pregnant mice before
      day 13 of gestation. This point in gestation marks the completion of the
      migration of germ cells to the gonadal ridge in mice and other studies with these
      mice have shown that the tumours are initiated in this critical time period. EE
      mixed with corn oil was administered by subcutaneous injection in doses of 0.02
      (n = 76) and 0.2 (n = 102) mg kg-1 of body weight on gestational days 11 and 12.
      These mice were allowed to deliver their offspring and the males were killed at
      15 days of age. Since the tumours are present from birth, this amount of time was
      allowed to permit the tumours to reach sufficient size for easy visual
      identification. Compared to controls (n = 63), who received corn oil alone, the
      treated mothers produced offspring who were significantly more likely to have a
      cryptorchid testis (P = 0.0001) and who had an increased risk, although not
      significant, of a testicular teratoma.

PMID- 1977468
TI  - Treatment of patients with metastatic pancreatic and gastrointestinal tumours
      with the somatostatin analogue Sandostatin: a phase II study including endocrine
      effects.
AB  - Somatostatin analogues can suppress the secretion of some gastrointestinal
      hormones and growth factors involved in the growth regulation of gastrointestinal
      cancers and can inhibit the growth of experimental pancreatic tumours. Therefore,
      in a phase II study 34 patients with metastatic pancreatic (n = 14), colorectal
      (n = 16) and gastric cancer (n = 4) were treated with three daily subcutaneous
      injections of 100-200 micrograms of the somatostatin analogue Sandostatin (SMS
      201-995). All patients had an extensive tumour load and 13 were pretreated with
      chemotherapy. Before Sandostatin treatment the patients with pancreatic cancer
      showed a higher mean plasma concentration of GH (P less than 0.05) and a lower
      concentration of 'total' somatomedin-C (P less than 0.005) compared with patients
      with colorectal cancer; there was no significant difference between these two
      groups in plasma levels of directly assayable somatomedin-C, EGF/TGF-alpha,
      insulin and prolactin. Within 3 days after start of treatment, somatomedin-C
      levels initially decreased (without a change in basal plasma GH levels), but
      returned to pretreatment levels within 4-13 weeks. Plasma insulin levels also
      were suppressed but only during the first 3-5 days of treatment. Plasma EGF-TGF
      alpha levels increased significantly at day 5 of treatment only in the pancreatic
      cancer patients. Twenty-seven per cent of the patients showed stable disease for
      3-9 months, but most patients experienced subjective improvement in the absence
      of serious side-effects. However, the overall survival remained disappointing,
      emphasising the need for better treatment regimens.

PMID- 1977469
TI  - The utility of a HindIII polymorphism of factor VIII examined by rapid DNA
      analysis.
AB  - A previously described HindIII restriction fragment length polymorphism (RFLP) of
      factor VIII (FVIII) has its polymorphic site in the unsequenced nineteenth
      intron. We have located the polymorphic site, as well as an invariant site, by
      amplifying and sequencing IVS 19 using the polymerase chain reaction (PCR). The
      oligonucleotide primers were synthesized from known FVIII sequence on either side
      of the 19-20 splice junction. The amplified product was cloned into a plasmid and
      sequenced by the dideoxy chain termination method. The polymorphic HindIII site
      was 103 bp and the invariant site 184 bp from the 3' end of the nineteenth exon.
      The frequency of the polymorphism was determined in 457 subjects (643
      chromosomes) of seven ethnic groups on whom frequency of the BclI RFLP of IVS 18
      was also assessed. The HindIII site is highly polymorphic in all groups,
      approximately 0.25:0.75, the expected heterozygosity averaging 37.6%, and the
      observed number of heterozygotes did not differ significantly from expectation.
      The (+):(-) allelic ratio is similar in all groups, except African-Americans in
      whom it is reversed. Strong allelic association (linkage disequilibrium) is
      present between the HindIII polymorphism of IVS 19 and the BclI polymorphism of
      IVS 18.

PMID- 1977470
TI  - XV Congress of the European Society for Medical Oncology. December 2-5, 1990,
      Copenhagen, Denmark. Abstracts.

PMID- 1977471
TI  - The mitochondrial aspartate/glutamate and ADP/ATP carrier switch from obligate
      counterexchange to unidirectional transport after modification by SH-reagents.
AB  - The influence of various SH-reagents on the aspartate/glutamate carrier was
      investigated in the reconstituted system. When liposomes carrying partially
      purified carrier protein were treated with 5,5'-dithiobis(2-nitrobenzoic acid) or
      N-ethylmaleimide, antiport activity was strongly reduced. Several mercury
      compounds exerted a dual effect. They completely blocked the antiport and, in
      addition, induced an efflux pathway for internal aspartate. The maximum rate of
      this unidirectional flux was comparable to the original antiport activity.
      Induction of efflux always was coupled to inhibition of antiport. Efflux was
      neither due to unspecific leakage of proteoliposomes nor to a possible
      contamination by porin, but depended on active carrier protein, as elucidated by
      the sensitivity to proteinases and protein-modifying reagents. Besides efflux of
      aspartate, HgCl2 and mersalyl also induced a slow efflux of ATP from liposomes
      carrying coreconstituted aspartate/glutamate and ADP/ATP carrier. The two efflux
      activities could be discriminated taking advantage of the differential
      effectiveness of several inhibitors and proteinases. Although basic carrier
      properties were changed by the applied mercurials (Dierks, T., Salentin, A. and
      Kramer, R. (1990) Biochim. Biophys. Acta 1028, 281), aspartate and ATP efflux
      could clearly be correlated with the aspartate/glutamate and the ADP/ATP carrier,
      respectively. When purifying these two translocators the respective efflux
      activity copurified with the antiporter, thus elucidating that the two different
      transport functions are mediated by the same protein. These results argue for a
      participation of the aspartate/glutamate and the ADP/ATP carrier in the generally
      observed increase of mitochondrial permeability after treatment with SH-reagents.

PMID- 1977472
TI  - Ultrastructural alterations in plasma membranes from drug-resistant P388 murine
      leukemia cells.
AB  - Freeze-fracture studies of daunomycin-sensitive and daunomycin-resistant P388
      cell lines, reveal a significant increase in the numerical density of
      intramembrane particles at both, the protoplasmic and the exoplasmic leaflets of
      the plasma membrane from the drug-resistant cells. Such change in plasma membrane
      architecture is not accompanied by overexpression of P-glycoproteins.
      Furthermore, drug-sensitive cells exhibited an increased number of exo
      endocytotic images when compared to drug-resistant cells. Our observations
      suggest that there are global changes in the structural organization of the
      plasma membrane, which are related to the acquisition of the cellular drug
      resistant phenotype.

PMID- 1977473
TI  - Regulation of the plasma membrane potential in hepatocytes--mechanism and
      physiological significance.

PMID- 1977474
TI  - Cloning of a Chinese hamster protein homologous to the mouse t-complex protein
      TCP-1: structural similarity to the ubiquitous 'chaperonin' family of heat-shock
      proteins.
AB  - The complete cDNA sequence of a Chinese hamster ovary cell protein, homologous to
      a mouse t-complex protein, TCP-1, has been determined. The deduced amino acid
      sequences of the mouse/Chinese hamster TCP-1 proteins exhibit significant
      identity to the 60-65 kDa heat shock 'chaperonin' family of proteins present in
      prokaryotes and in the eukaryotic cell organelles.

PMID- 1977475
TI  - Neurotransmitters and stress.
AB  - In this article definitions of stress and distress are proposed and the
      relationships between stress and activities of neurohormonal systems explored.
      The idea is developed that stress is a condition where expectations--whether
      genetically programmed, established by prior learning, or deduced from
      circumstances--do not match the current or anticipated perceptions of the
      internal or external environment, and this discrepancy between what is observed
      or sensed and what is expected or programmed elicits patterned, compensatory
      responses. Distress is viewed here as a form of stress characterized by specific
      behavioral and autonomic communicated signs, pituitary-adrenocortical and
      sympathoadrenomedullary activation, and a negative experience that motivates
      escape or avoidance. During stress, many body systems--including the
      sympathoadrenal, parasympathetic, and hormonal homeostatic systems--are activated
      or inhibited in primitively specific patterns regulated by physiological,
      biochemical, and psychological homeostats. Many of these patterns, which are at
      least partly inherited, can be understood teleologically on the basis of
      preservation of the internal environmental and natural selection in evolution.

PMID- 1977476
TI  - [Cardiac guanylate cyclase in rats with ischemic damage to the myocardium].
AB  - The activity of soluble guanylate cyclase (GC) of rat heart and the regulatory
      activity of dithiothreitol (DTT) and sodium nitroprusside under ischemic
      myocardium damage caused by ligation of left coronary artery has been
      investigated. After coronary occlusion the GC activity in the presence of Mn2+ or
      Mg2+ decreases both in ischemic and in intact zones (40% from normal) in 15 min,
      in 24 h it more diminishes (up to 30%) in the ischemic zone, in intact zone it
      partially normalizes (up to 70%). The stimulatory effect of DTT on the GC
      activity in studied heart zones doesn't differ from control. The activation of GC
      by nitroprusside in ischemic zone decreases in 15 min, it is practically absent
      in 24 h. The decrease of GC activation in intact zone is less expressed. It is
      suggested that the reduction of GC activation by sodium nitroprusside is due to
      the loss of the heme by the enzyme during ischemia.

PMID- 1977477
TI  - The platelet polyphosphoinositide system in schizophrenia: the effects of
      neuroleptic treatment.
AB  - Signal transduction, mediated by the thrombin-stimulated polyphoshoinositide
      (PPI) turnover was studied in platelets from 44 schizophrenic patients and 33
      healthy volunteers. The stimulated generation of inositol phosphates in the
      schizophrenic group was significantly greater than that in the control group.
      There was a lack of correlation between this augmented response and a variety of
      clinical parameters. The response in 9 drug-naive schizophrenic patients was not
      significantly different from that in controls. The response was significantly
      augmented in patients receiving neuroleptic treatment and in patients who had
      been off neuroleptics for at least 4 months. These results indicate that
      neuroleptic treatment may produce a long-term modification of signal transduction
      via the PPI system. Further studies are required to elucidate the exact nature of
      this modification and to explore the possibility that this effect of the
      neuroleptics may provide a novel approach to understanding the neurochemistry of
      schizophrenia and to monitoring the neuroleptic treatment.

PMID- 1977478
TI  - Cigarette smoking and neuroleptic-induced parkinsonism.
AB  - Several studies have reported an apparent protective effect of cigarette smoking
      for the risk of idiopathic Parkinson's disease (IPD). These observations are
      supported by neurochemical studies demonstrating enhancement of central
      dopaminergic neurotransmission by nicotine. We studied the prevalence and
      severity of neuroleptic-induced parkinsonism (NIP) in relation to cigarette
      smoking in a homogeneous sample of 130 psychiatric inpatients receiving long-term
      neuroleptic treatment. Despite the fact that smokers had significantly higher
      dosage of neuroleptics during the month prior to evaluation and longer exposure
      to medication, they presented with significantly less prevalence and severity of
      NIP than nonsmokers. These findings suggest that the inverse association between
      smoking and IPD may apply to NIP.

PMID- 1977480
TI  - Twenty-third congress of the International Society of Hematology and the thirty
      second annual meeting of the American Society of Hematology. November 28-December
      4, 1990. Boston, MA. Abstracts.

PMID- 1977479
TI  - 5-HT1A receptor responsivity in unipolar depression. Evaluation of ipsapirone
      induced ACTH and cortisol secretion in patients and controls.
AB  - The selective 5-HT1A receptor ligand ipsapirone (IPS) induces corticotropin
      (ACTH) and cortisol secretion in humans. To explore 5-HT1A receptor-mediated
      hypothalamic-pituitary-adrenal (HPA) system activation in depression, 24 subjects
      (12 patients with unipolar depression and 12 individually matched controls) were
      given 0.3 mg/kg IPS or placebo in random order. Compared with controls, the
      depressed patients exhibited significantly decreased ACTH and cortisol responses
      to IPS in association with increased basal cortisol secretion. The impaired HPA
      response following 5-HT1A receptor challenge in unipolar depression could have
      resulted from glucocorticoid-dependent subsensitivity of the (post-synaptic) 5
      HT1A receptor itself and/or from a defective postreceptor signaling pathway
      [inhibitory guanine nucleotide-binding protein (Gi)-adenylate cyclase complex
      function], thus supporting the hypothesis that a disintegrated 5-HT and HPA
      system interaction may be present in depression. Future studies of the HPA
      response to direct-acting 5-HT1A ligands, such as IPS, should facilitate the
      assessment of 5-HT/HPA system integrity in various affective disorders and its
      involvement in psychotropic drug effects.

PMID- 1977481
TI  - HLA class II genes: typing by DNA analysis.
AB  - A detailed understanding of the structure and function of the human major
      histocompatibility complex (MHC) has ensued from studies by molecular biologist
      during the last decade. Virtually all of the HLA genes have now been cloned, and
      the nucleotide sequences of their different allelic forms have been determined.
      Typing for these HLA alleles is a fundamental prerequisite for tissue matching in
      allogeneic organ transplantation. Until very recently, typing procedures have
      been dominated by serological and cellular methods. The availability of cloned
      DNA from HLA genes has now permitted the technique of restriction fragment length
      polymorphism (RFLP) analysis to be applied, with remarkable success and
      advantage, to phenotyping of both HLA Class I and Class II determinants. For the
      HLA Class II genes DR and DQ, a simple two-stage RFLP analysis permits the
      accurate identification of all specificities defined by serology, and of many
      which are defined by cellular typing. At the present time, however, RFLP typing
      of HLA Class I genes is not as practicable or as informative as that for HLA
      Class II genes. The present clinical applications of HLA-DR and DQ RFLP typing
      are predominantly in phenotyping of living donors, including selection of HLA
      matched volunteer bone marrow donors, in allograft survival studies, and in
      studies of HLA Class II-associated diseases. However, the time taken to perform
      RFLP analysis precludes its use for the typing of cadaveric kidney donors.
      Nucleotide sequence data for the alleles of HLA Class II genes have now permitted
      the development of allele-specific oligonucleotide (ASO) typing, a second
      category of DNA analysis. This has been greatly facilitated by the ability to
      amplify specific HLA Class II DNA 'target' sequences using the polymerase chain
      reaction (PCR) technique. The accuracy of DNA typing techniques should ensure
      that this methodology will eventually replace conventional HLA phenotyping.

PMID- 1977482
TI  - Guidelines for management of asthma in adults: I--Chronic persistent asthma.
      Statement by the British Thoracic Society, Research Unit of the Royal College of
      Physicians of London, King's Fund Centre, National Asthma Campaign.

PMID- 1977483
TI  - Nephrotic syndrome associated with sulphasalazine.

PMID- 1977484
TI  - Upper gastro-intestinal complications in major head and neck surgery.
AB  - The recovery of patients from major head and neck surgery can be compromised by
      severe upper gastro-intestinal complications. We present two cases with such
      problems and discuss the rationale for our current management of prophylaxis.

PMID- 1977485
TI  - The (frequently) neuroleptic (potentially) malignant syndrome.

PMID- 1977487
TI  - Aggressiveness, anxiety and drugs.

PMID- 1977486
TI  - Rabbit syndrome--a rare complication of long-term neuroleptic medication.
AB  - A case of rabbit syndrome, a complication of long-term neuroleptic medication, is
      reported. It is important to differentiate it from tardive dyskinesia and
      continuous therapy with an antiparkinsonian agent may be required for control of
      symptoms of rabbit syndrome.

PMID- 1977488
TI  - Immunogenetics of polymyalgia rheumatica.
AB  - Evidence suggests that polymyalgia rheumatica (PMR) may be an immune-mediated
      disease. Therefore, the role of HLA class II genes, the switch region of
      immunoglobin mu and alpha 1 heavy chain as the T-cell receptor (TcR) genes were
      investigated by Southern blot analysis. The frequency of DR4 specificity was
      increased in PMR (67.4% versus 30.3%; P = 0.00017). No association was found with
      the DQA and DQB genes, the switch region of immunoglobulin mu and alpha 1 heavy
      chain genes, and the TcR alpha, beta and gamma genes. This study suggests that
      HLA-DR4 is an important susceptibility factor for PMR. Further studies are needed
      to elucidate the role of Ig and TcR genes.

PMID- 1977489
TI  - Long-term radiographic progression in treated rheumatoid arthritis.

PMID- 1977490
TI  - Neutropenia in patients with rheumatoid arthritis, treated with sulphasalazine.

PMID- 1977491
TI  - Torsion of the vas aberrans.

PMID- 1977492
TI  - Recurrent torsion of the testis.

PMID- 1977494
TI  - Dopaminergic antagonists prevent long-term maintenance of posttetanic LTP in the
      CA1 region of rat hippocampal slices.
AB  - The involvement of dopaminergic mechanisms in the induction and maintenance of
      posttetanic long-term potentiation (LTP) was investigated on CA1 cells of rat
      hippocampal slices. The presence of the dopamine receptor blocker domperidone in
      a concentration of 1 microM during tetanization with 3 trains of 100 impulses
      (100 Hz) and a train interval of 10 min influences neither the synaptic
      transmission nor the induction of LTP. However, the potentiation of both the
      population spike and the population EPSP gradually decreases, thus significantly
      differing from control LTP about 4 h after initiation and reaching the level of
      non-tetanized controls about 7-8 h after tetanization. The simultaneous presence
      of 1 microM apomorphine during tetanization abolishes this effect of domperidone
      indicating the specific dopaminolytic nature of its action. Also the presence of
      the dopamine antagonists sulpiride and flupenthixol, respectively, in a
      concentration of 1 microM during tetanization likewise prevents the occurrence of
      the late LTP maintenance. The determination of [14C]dopamine in 2 min fractions
      from the superfused slices after preloading during a preincubation period
      revealed that a low frequency stimulation of the Schaffer collaterals with 0.33
      Hz does not influence the spontaneous efflux of dopamine, whereas the
      tetanization with an impulse train of 100 Hz produces a significantly enhanced
      release. The observations suggest that dopaminergic influences during and
      immediately after tetanization at least additionally contribute to the induction
      of postsynaptic mechanisms subserving a late, long-lasting maintenance of
      potentiation. The results also support the assumed existence of different
      subsequent stages of LTP.

PMID- 1977493
TI  - Action of the anti-ischemic agent ifenprodil on N-methyl-D-aspartate and kainate
      mediated excitotoxicity.
AB  - The efficacy of ifenprodil to antagonize N-methyl-D-aspartate (NMDA) and kainate
      (KA)-induced acute excitotoxicity was evaluated in embryonic day 13 chick retina.
      Incubation with either 50 microM NMDA or KA produced a characteristic
      histological lesion and release of endogenous gamma-aminobutyric acid (GABA).
      Ifenprodil potently attenuated NMDA-induced GABA efflux by 80% (IC50, 1.26
      microM). Histology showed protection of all but a subpopulation of amacrine
      neurons and processes even at 500 microM ifenprodil. MK-801 and CGS 19755,
      uncompetitive and competitive NMDA antagonists, respectively, protected all NMDA
      sensitive amacrines, including the ifenprodil-resistant population, whilst CNQX,
      a non-NMDA glutamate receptor antagonist, was ineffective. Ifenprodil was less
      effective versus KA, requiring 10-100-fold higher concentrations to significantly
      attenuate GABA release. The potent antagonism of NMDA-mediated acute
      excitotoxicity by ifenprodil may explain its efficacy as an anti-ischemic agent.
      Ifenprodil does, however, leave unprotected a subpopulation of NMDA-susceptible
      neurons suggesting a heterogeneity in the NMDA receptor population.

PMID- 1977495
TI  - The binding of somatostatin to the mouse retina is altered by the pearl mutation.
AB  - Pearl mutants have a night-blind phenotype and abnormal optokinetic nystagmus.
      Preliminary results from another study showed that the light responses of retinal
      ganglion cells of pearl mutant mice were affected by bathing the isolated retina
      with low (less than 1 nM) concentrations of either somatostatin-14 or -28,
      whereas the responses in wild-type retinas were affected only by somatostatin-28.
      In order to test the possibility that these physiological differences resulted
      from alterations in receptor affinity, we studied the binding of 125I-[Tyr11]
      somatostatin-14 and 125I-[Leu8,D-Trp22,Tyr25]-somatostatin-28 to frozen, unfixed
      sections of eyes of wild-type (C57BL/6J +/+) and congenic pearl mutant (C57BL/6J
      pin pe(pin)/pe(pin)) mice. As found previously for wild-type mice, specific
      binding occurred in 3 maxima in pearl mutants: a broad band extending from the
      retinal ganglion cell to the inner nuclear layer, a narrow and inconstant band
      over the outer plexiform layer, and a band over the pigment epithelium and
      choroid. We quantified the label over the inner plexiform layer and found
      evidence for a single saturable site in both genotypes. However, several results
      indicate that somatostatin-14 binds more avidly to pearl mutant retinas than to
      wild-type retinas. In saturation binding studies, Kd for 125I-[Tyr11]
      somatostatin-14 was 600 pM in pearl mutants vs 1.5 nM in wild-type; whereas, for
      125I-[Leu8,D-Trp22,Tyr25]-somatostatin-28, Kd was nearly equal in the two
      genotypes (500 and 625 pM, respectively). Bmax was nearly equal for both ligands
      in both genotypes (63-69 fmol/mg protein).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1977496
TI  - Dynorphin A-containing neural elements in the nucleus of the solitary tract of
      the rat. Light and electron microscopic immunohistochemistry.
AB  - Distribution of dynorphin A (DyA) immunoreactivity in the nucleus of the solitary
      tract (NTS) was examined in rats after various surgical transections by light and
      electron microscopic immunohistochemistry. In colchicine-treated animals DyA
      immunostained perikarya were seen in each subdivision of the NTS. In intact rats,
      dense network of immunopositive nerve fibers was localized light microscopically,
      and synaptic contacts were found between DyA immunopositive structures (axo
      axonic, axo-dendritic synapses), electron microscopically. Surgical transections
      medial, caudal or rostral to the nucleus did not alter the distribution pattern
      of DyA in the NTS. Lesion immediately lateral to the nucleus resulted in an
      ipsilateral appearance of immunostained cell bodies. Vagal and glossopharyngeal
      afferents (including baroreceptor fibers) terminate in the medial and commissural
      subnucleus of the NTS. Two days after extracranial vagotomy, synaptic contacts
      between degenerated presynaptic boutons and DyA immunopositive postsynaptic
      elements were observed in both medial and commissural part of the NTS. These
      observations provide morphological evidence suggesting that (1) axons of
      dynorphin A-containing cell bodies form an intrinsic network inside the nucleus;
      (2) these DyA cells receive direct peripheral inputs through the vagus nerve, and
      (3) projecting DyA neurons may exist in the NTS, they may innervate medullary,
      rather than forebrain, higher brainstem or spinal cord neurons.

PMID- 1977497
TI  - Reduced density of striatal somatostatin receptors in Huntington's chorea.
AB  - A marked increase of the endogenous somatostatin has been reported in the
      striatum in Huntington's chorea by radioimmunoassay and immunohistochemistry.
      Using quantitative receptor autoradiography we examined the density and
      distribution of somatostatin receptors in the striatum of 6 patients dying from
      Huntington's chorea degree 3, in 12 control healthy patients dying without
      neurological diseases and 7 schizophrenic patients, using the stable somatostatin
      octapeptide analogue [125I]204-090 as a radioligand. Marked reductions of the
      density of somatostatin binding sites were observed in the caudate and putamen of
      all patients with Huntington's chorea. However, these receptors were well
      preserved in the nucleus accumbens and in the ventral aspects of the anterior
      putamen. No alteration of somatostatin receptors was observed in other brain
      areas. These results suggest that somatostatin receptors in the human striatum
      are markedly down-regulated or localized on a population of neurons which is at
      risk in Huntington's chorea and questions the postulated role for the elevated
      somatostatin levels in choreiform movements.

PMID- 1977498
TI  - Sleep variables are unaltered by zolantidine in rats: are histamine H2-receptors
      not involved in sleep regulation?
AB  - The effects of the H1-receptor antagonist diphenhydramine and the brain
      penetrating H2-receptor antagonist zolantidine were studied in rats implanted for
      chronic sleep recordings. Diphenhydramine (1.0-4.0 mg/kg) significantly increased
      slow wave sleep and decreased wakefulness. Zolantidine (0.25-8.0 mg/kg) had no
      significant effects on any of the sleep parameters examined. One possibility is
      that zolantidine did not enter the brain in sufficient concentration to produce
      significant changes on sleep and wakefulness. Another possibility is that
      blockade of H2-receptor involved parts of the brain other than those implicated
      in the sleep-wake cycle. The feasibility remains that H2-receptors are not
      involved in sleep regulation. The absence of selective, brain-penetrating H2
      receptor agonists precludes a more detailed analysis of the role of this subtype
      of receptor in the control of sleep and wakefulness.

PMID- 1977499
TI  - Behavioral and electrophysiological correlates of human mesencephalic
      dopaminergic xenograft function in the rat striatum.
AB  - While human fetal xenografts placed into immunocompromised animal hosts have been
      shown to survive and grow, their ability to function and influence the host
      tissue has not been fully examined. Therefore, we implanted grafts of human fetal
      mesencephalic tissue intracranially into rats with unilateral 6-hydroxydopamine
      lesions of their nigrostriatal dopaminergic innervation and tested the rats
      behaviorally for reductions in apomorphine-induced rotations. The purpose of this
      study was to test the ability of these grafts to provide a functional
      reinnervation by comparing the behavioral changes with the morphology and
      presence of electrophysiologically active dopaminergic neurons within the graft
      and with firing rates of host striatal neurons. Adult Sprague-Dawley rats that
      had been unilaterally lesioned and that showed a stable two peak pattern of
      apomorphine-induced rotations received grafts of human fetal mesencephalic tissue
      placed directly into the lesioned striatum. These rats were then further tested
      each month for five months for reductions in their turning behavior. At 5 to 6
      months postgrafting, electrophysiological recordings were made of cells within
      the graft and within the host striatum. The rats were then examined
      immunohistochemically to evaluate graft survival and extent of reinnervation of
      the host tissue. The rats receiving mesencephalic dopaminergic grafts
      demonstrated a 79% reduction in their apomorphine-induced rotations.
      Electrophysiological recordings revealed spontaneously active dopaminergic
      neurons within the graft as well as host striatal cell firing rates consistent
      with those of dopamine-innervated cells. Furthermore, immunohistochemical studies
      confirmed graft survival and revealed marked fiber outgrowth from the graft into
      and throughout the striatum. Taken together these findings provide evidence that
      grafts of human fetal mesencephalic tissue are able to produce behavioral
      improvements in lesioned animals which are associated with the presence of
      dopaminergic neurons within the graft and are consistent with normal host
      striatal cell activity levels.

PMID- 1977500
TI  - [D2 dopaminergic receptor activation enhances the spontaneous release of 3H-GABA
      in the prefrontal cortex of rats, in vitro. The facilitating role of D1
      dopaminergic receptors].
AB  - The effects of three D2 dopaminergic agonists on the spontaneous release of 3H
      GABA have been studied on rat prefrontal cortical slices. LY171555 (10(-9) M),
      RU24926 (3 x 10(-8) M) and lisuride (10(-7) M) respectively enhanced the
      spontaneous release by 25, 20.5 and 23%. These effects were totally reversed by
      the D2 antagonist sulpiride (10(-5) M). Furthermore, subliminar concentration of
      RU24926 (10(-9) M) and of the D1 agonist SKF38393 (10(-6) M) induced a clear
      enhancement of the spontaneous release of 3H-GABA when they were superfused
      simultaneously. Our results suggest that in the prefrontal cortex, the
      spontaneous release of 3H-GABA is under an activatory D2 dopaminergic control.
      The activation of D1 receptors seems to have an enabling effect on this
      regulation.

PMID- 1977501
TI  - Isolation and characterization of spore coat protein (sp96) gene of Dictyostelium
      discoideum.
AB  - A cDNA library was constructed from poly(A)+ RNA isolated from slug cells of
      Dictyostelium discoideum, using lambda gt11 phage, and screened with an antiserum
      specific for the spore coat protein sp96. A positive clone was obtained and the
      gene product was identified as sp96. The sp96 mRNA is 2.2 kb in size, and it
      starts to accumulate at the tipped aggregate stage only in prespore cells.
      Southern analysis using nuclear DNA established that the sp96 gene is unique. Two
      genomic clones containing the sp96 gene were isolated and the sequence of the
      gene established. The coding region contains a long open reading frame
      interrupted by a single intron.

PMID- 1977502
TI  - Human HOX genes are differentially activated by retinoic acid in embryonal
      carcinoma cells according to their position within the four loci.
AB  - We studied the expression of 33 human homeobox genes belonging to four complex
      HOX loci in embryonal carcinoma NT2/D1 cells. These cells can be induced to
      differentiate by culturing them in media containing retinoic acid. Northern blot
      analysis reveals that no expression of these genes was detectable in NT2/D1 stem
      cells, whereas 22 HOX genes are well expressed in NT2/D1 cells treated with 10
      microM retinoic acid for 14 days. The 11 HOX genes the expression of which
      remained undetectable in NT2/D1 cells after this treatment are located at the 5'
      end of their loci: four in HOX1, five in HOX3 and two in HOX4. The boundary
      between induced and silent genes roughly corresponds to the HOX genes
      constituting the homology group 5, related to the Abdominal-B homeotic gene of
      Drosophila. All nine identified HOX2 genes are well expressed in fully induced
      NT2/D1 cells and none of them maps 5' genes of this homology group. We conclude
      that HOX genes are differentially activated by retinoic acid in these cells
      according to their physical location within the four chromosomal loci.

PMID- 1977503
TI  - [Role of thromboxane A2 and prostacyclin in the pathophysiology of epidemic
      hemorrhagic fever].

PMID- 1977504
TI  - Antihistamines reassessed. XIVth Congress of the European Academy of Allergology
      and Clinical immunology. Berlin. Proceedings.

PMID- 1977505
TI  - New H1-receptor antagonists: clinical pharmacology.
AB  - The non-sedating, second-generation H1-receptor antagonists such as terfenadine,
      astemizole, loratadine and cetirizine differ considerably from each other in
      their pharmacokinetics and pharmacodynamics. They are generally well absorbed
      when administered orally. They have extremely variable serum elimination half
      life values. The maximum antihistaminic effect of these medications occurs
      several hours later than peak serum concentrations do. The duration of the
      antihistaminic effect is much longer than would be predicted from the serum
      elimination half-life values. The relative incidence of anticholinergic and
      central nervous system adverse effects caused by these medications is similar to
      that produced by placebo. The introduction of the second-generation H1-receptor
      antagonists represents a major advance in symptomatic therapy of allergic
      disorders such as allergic rhinitis and urticaria.

PMID- 1977506
TI  - Histamine and asthma: an appraisal based on specific H1-receptor antagonism.
AB  - H1-receptor antagonists have been utilized, following their initial chemical
      synthesis in 1933, both in the treatment of conditions in which histamine is
      considered to be of pathogenic importance and conversely to help elucidate the
      role of histamine in disease, through an evaluation of their influence on disease
      expression. While there is considerable indirect evidence to implicate histamine
      in the pathogenesis of asthma, a critical evaluation of H1-receptor antagonism in
      this condition has, until recently, proved difficult, as many of the early H1
      receptor antagonists possessed additional actions, such as anti-cholinergic,
      local anaesthetic, alpha-adrenoceptor antagonistic and anti-serotonin activity.
      In addition, H1-receptor antagonists have been shown to have effects on mast cell
      function. In low concentrations in vitro, antihistamines have been found to
      inhibit immunologically stimulated mast cell mediator release, with the IC50 in
      the nanomolar to micromolar range, while at higher concentrations they induce
      histamine release. The potency of these drugs in producing such effects is
      unrelated to their H1-receptor blocking activity. Furthermore the sedative
      effects of these therapeutic agents limit the tolerable administrable dose and
      thus the degree of H1-receptor blockade achievable within the airways. The recent
      development of H1-receptor antagonists devoid of clinical sedative effects has
      enabled the administration of doses of H1-antihistamines which achieve a greater
      degree of H1-receptor blockade within the airways, thus permitting a better
      appraisal of the role of histamine in this condition. Furthermore, the receptor
      specificity of many of these agents has been focused such that terfenadine,
      astemizole, loratadine and cetirizine are devoid of anticholinergic activity and
      exhibit little alpha-antagonistic or anti-serotonin activity of clinical
      relevance. However, of these agents both loratadine and cetirizine possess
      additional actions likely to be of relevance to asthma. Pretreatment with
      loratadine has been shown to reduce the recovery of both histamine and
      prostaglandin D2 (PGD2) in nasal lavage fluid following nasal allergen challenge,
      a finding interpreted as indicative of in vivo mast cell stabilization, and
      cetirizine has been shown in vivo at therapeutic doses to inhibit allergen
      induced eosinophil chemotaxis. Thus while both these agents offer the potential
      of an oral therapy for asthma based on an H1-receptor antagonist, their
      additional actions do not make them ideally suited to the exploration of the role
      of histamine in asthma.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1977507
TI  - H1- and H2-antagonists in allergic and pseudoallergic diseases.
AB  - Although known for more than 80 years, histamine still remains a fascinating
      substance for allergy research. Histamine antagonists have been in clinical use
      since 1942. The classical H1-antagonists with sedative side-effects have been
      more or less replaced by newer non-sedating H1-antagonists; the role of H2
      receptors in allergic diseases is still controversial. There, are however,
      increasing reports of beneficial effects of H2-antagonists, mostly in combination
      with H1-antagonists, in a variety of allergic and pseudoallergic conditions such
      as chronic urticaria, anaphylactoid reactions due to colloid volume substitutes,
      opioid analgesics and radiographic contrast media. The combined use of H1- and H2
      antagonists might not only act as specific histamine antagonism but exert a mast
      cell stabilizing effect, as demonstrated in animal experiments and some clinical
      studies. Future research will show whether the combined use of H1- and H2
      antagonists will become a routine therapeutic procedure in allergy therapy.

PMID- 1977508
TI  - Does the clinical experience with non-sedating H1-antagonists justify a
      reassessment of antihistamines in allergy treatment?
AB  - Although antihistamines were usually considered as ineffective in asthma, the
      appearance of new more potent anti-'1-antagonists with no or less side-effects
      leads to a reassessment of their use. Although mediators and mechanisms other
      than histamine are involved in natural or provoked reactions to allergens in the
      skin, the nose or the lungs, the new anti-H1-antagonists have been shown to be
      effective. For some of these drugs, the effect may go beyond a mere H1-receptor
      blockade and involve impairment of mediator release from mast cells and/or an
      inhibiting effect on other cell types (e.g. eosinophils) implicated in the late
      phase reactions. Quantitative kinetics evaluation of late-phase reactions in the
      skin and of their inhibition by anti-allergic drugs will be helped considerably
      by the development of telethermography, a new skin evaluation technique.

PMID- 1977509
TI  - Preventing alcohol problems: the challenge for medical education. Proceedings of
      a national conference. Niagara-on-the-Lake, October 16-17, 1989.

PMID- 1977510
TI  - Third World issues provide sobering backdrop as emergency physicians meet. Third
      International Conference on Emergency Medicine.

PMID- 1977512
TI  - Verapamil and cyclosporin A potentiate the effects of chemotherapeutic drugs in
      the human medullary thyroid carcinoma TT cell line not expressing the 170 kDa P
      glycoprotein.
AB  - The TT-cell line, derived from a patient with metastatic medullary thyroid
      carcinoma (MTC), was found to exhibit intrinsic resistance to vincristine (VCR)
      despite the absence of immunohistochemically detectable 170 kDa P-glycoprotein
      (PGP 170) associated with multidrug resistance (MDR). Verapamil and cyclosporin
      A, two well known resistance modifiers of MDR, were found to significantly
      potentiate the action of VCR (60-fold) and to a lesser degree also of VP-16 and
      daunorubicin (dnr). The present results suggests that resistance of MTC to
      chemotherapy may be at least partly circumvented by the addition resistance
      modifiers to chemotherapeutic regimens.

PMID- 1977513
TI  - Absence of the c-Ha-ras codon 61 point mutation in murine solid tumors induced by
      subcutaneously applied 7,12-dimethylbenzanthracene.
AB  - The c-Ha-ras-1 codon 61 A----T transversion is a highly consistent finding in
      murine skin DMBA-initiated/TPA-promoted papillomas and carcinomas. We performed
      Xba I RFLP analysis on DNA from clonal cell lines derived from 11 independent
      papillomas and a single carcinoma derived from topically applied DMBA and
      compared this to RFLP on DNA from 7 clonal fibrosarcoma cell lines derived from
      tumors arising after subcutaneous administration of the same carcinogen. The A---
      T point mutation was present in all of the papillomas and carcinoma derived by
      the classic DMBA-TPA protocol but was absent in all of the fibrosarcomas arising
      after subcutaneous administration of DMBA.

PMID- 1977511
TI  - Candida albicans strain delineation.
AB  - Candida albicans is a major opportunistic pathogen causing a wide spectrum of
      disease in human beings. Methods for strain delineation of this species to assess
      or predict virulence or to conduct epidemiologic or pathogenetic investigations
      have been developed. Although factors associated with virulence have been
      identified, there is no rapid system to quantitate them in a clinical laboratory.
      Therefore, many typing methods are based on variable phenotypic characteristics
      within this species including morphotyping, serotyping, antibiogram, resistogram
      typing, biotyping, biotyping based on commercial carbon assimilation patterns,
      enzyme profiles, sensitivity to yeast killer toxins, and typing based on protein
      variability. Phenotypically defined strains generally do not correlate with the
      pathogenic potential of a strain with the exception of morphotyping. However,
      these methods can be useful in epidemiologic investigations; for example, they
      have revealed that most individuals harbor one strain and that infections are
      frequently due to an endogenous strain. Problems with these methods usually
      relate to their discriminatory power. When this is maximized, reproducibility
      (especially between laboratories) suffers. Recently, methods based on differences
      in DNA structure (genotyping) for strain delineation have been developed,
      including electrophoretic karyotyping and restriction enzyme fragment length
      polymorphisms. The development of a computer-assisted data bank and analysis for
      these genotypic strain delineators will open investigations into the pathogenesis
      of this infection and permit epidemiologic studies previously not possible with
      this important human pathogen.

PMID- 1977514
TI  - Genetic changes and histopathological types in colorectal tumors from patients
      with familial adenomatous polyposis.
AB  - Loss of heterozygosity (LOH) and K-ras mutation were analyzed in 111 colorectal
      polyps and 26 invasive carcinomas from 40 patients with familial adenomatous
      polyposis of distinct histopathological types. LOH, being less than 2% in
      moderate adenomas, was detected on chromosome 5q (20%) in severe adenomas, on 5q
      (26%) and 17p (38%) in intramucosal carcinomas, and on 5q (52%), 17p (56%), 18
      (46%), and 22q (33%) in invasive carcinomas. LOH on chromosome 5q occurred most
      frequently in the region close to the APC gene both in adenomas and carcinomas,
      and a loss of the normal allele of the APC gene was demonstrated in 3 cases. K
      ras mutation markedly increased in the step of development from moderate (11%) to
      severe (36%) adenomas. These results suggest the following mechanisms for the
      development of colon tumors in patients with familial adenomatous polyposis: (a)
      the heterozygous mutant/wild-type condition at the APC gene causes formation of
      mild or moderate adenoma; (b) the loss of the normal allele in the APC gene leads
      to a change from moderate to severe adenoma; (c) LOH on chromosome 17p
      contributes to the conversion of adenoma to intramucosal carcinoma; (d) LOH on
      other chromosomes, such as 18 and 22q, are involved in the progression of
      intramucosal carcinoma to invasive carcinoma; and (e) K-ras mutation may also
      affect the development of moderate to severe adenoma.

PMID- 1977515
TI  - Allelotype of breast cancer: cumulative allele losses promote tumor progression
      in primary breast cancer.
AB  - Allele loss on a specific chromosome has implied the existence of a tumor
      suppressor gene such as the p53 gene and the RB gene. In order to determine which
      chromosome(s) carries a tumor suppressor gene(s) that contributes to tumor
      progression in primary breast cancer, we analyzed the loss of heterozygosity for
      each autosomal chromosome arm by using 39 restriction fragment length
      polymorphism markers including 25 variable numbers of tandem repeat probes. In 79
      primary breast cancers, we found the frequent loss on the long arm of chromosome
      13 (21%), the long arm of chromosome 16 (45%), and the short arm of chromosome 17
      (56%). Interestingly, breast cancers in which loss of both chromosomes 13q and
      17p was detected showed more malignant histopathological features, and a group of
      the tumors in which chromosome 16q loss was detected presented with frequent
      lymph node metastasis. Furthermore, the result of the deletion mapping on
      chromosome 17p implied the existence of a tumor suppressor gene distal to the p53
      gene as well as the p53 gene itself for primary breast cancer. These results
      suggest that at least 4 tumor suppressor genes exist on chromosomes 13q, 16q, and
      17p for primary breast cancer.

PMID- 1977516
TI  - High activity of mitochondrial glycerol phosphate dehydrogenase in insulinomas
      and carcinoid and other tumors of the amine precursor uptake decarboxylation
      system.
AB  - The activity of the mitochondrial glycerol phosphate dehydrogenase (EC 1.1.99.5),
      the enzyme unique to the glycerol phosphate hydrogen shuttle, was measured in
      normal human tissues and tumors and compared with the activity of succinate
      dehydrogenase, another enzyme that transfers electrons to ubiquinone at site II
      of the electron transport chain. Six of 7 insulinomas and 10 of 12 carcinoid
      tumors showed high glycerol phosphate dehydrogenase activity. The activity was
      also increased in 3 of 4 gastrinomas, 2 paraganglionomas, 1 of 4 thyroid nodules,
      and 1 parathyroid tumor. These tissues belong to the amine precursor uptake
      decarboxylation system. The activity of glycerol phosphate dehydrogenase was
      generally unremarkable in non-amine precursor uptake decarboxylation system
      tumors and in normal tissues studied. However, 1 of 2 breast carcinomas, 1
      submandibular tumor, and 2 of 3 melanomas were enriched in glycerol phosphate
      dehydrogenase activity. In general, succinate dehydrogenase activity exceeded
      that of glycerol phosphate dehydrogenase in all tissues except some of the
      tissues in which glycerol phosphate dehydrogenase activity was high. Normal
      tissues, such as the pancreatic beta-cell, which aerobically metabolize glucose
      rapidly utilize the glycerol phosphate shuttle to oxidize the large amount of
      NADH formed from glucose metabolism in the cytosol. Whether this is the reason
      for the enriched activity of the glycerol phosphate dehydrogenase in certain
      amine precursor uptake decarboxylation system tumors is unknown.

PMID- 1977517
TI  - Human colorectal cancer: high frequency of deletions at chromosome 1p35.
AB  - Cytogenetic analyses of human colon cancer cells have revealed a high frequency
      of chromosome 1p deletions among other chromosomal abnormalities. In order to
      find out whether these chromosomal alterations are manifestations of loss of
      genetic material, we surveyed DNA of 62 primary tumors, 7 metastases, and
      matching peripheral blood cells with a panel of polymorphic DNA probes that
      detect different loci on chromosome 1p. A portion of the probes was derived from
      a microclone bank generated by microdissection and microcloning of 1p35----pter
      DNA. In 42% of the colon carcinomas allelic loss was observed with at least one
      probe. The deletions were of different sizes but always included a region
      involving band 1p35, except for two tumors in which allelic loss was detected
      more proximally. The frequency of 1p deletion in the metastases was higher than
      in the primary tumors. These data indicate that genetic information related to
      tumorigenesis is located within or nearby region 1p35 and that deletion of this
      region occurs later in tumor development. Our results add to the number of
      genetic changes presumably involved in colon cancerogenesis.

PMID- 1977518
TI  - Tumor progression in four mammary epithelial cell lines derived from the same
      patient.
AB  - Two primary and two metastatic cell lines with distinct phenotypes and genotypes
      have been established from a patient diagnosed as having infiltrating and
      intraductal mammary carcinoma (21T series). All four lines can be cultured in the
      same medium, DFCI-1, which also supports long-term growth of normal epithelial
      cells. Therefore, we have been able to compare normal and tumor cells at the
      cellular and molecular levels. The mammary origin of the 21T series was confirmed
      by using antibodies against the human milk fat globule antigen-2 epitope. The two
      primary tumor lines (21NT and 21PT) are both immortal and aneuploid, although
      only 21NT is tumorigenic in the nude mouse assay. The two populations derived
      from the metastatic pleural effusion (21MT-1 and 21MT-2) each exhibit distinct
      characteristics in morphology and growth factor requirements. The erbB2 gene is
      amplified and overexpressed in all of these cell lines compared to normal
      epithelial cell controls. These four tumor cell lines from a single patient
      represent a mammary tumor progression series that has been established in long
      term cell culture.

PMID- 1977519
TI  - Resistance of human ovarian cancer cells to tumor necrosis factor and lymphokine
      activated killer cells: correlation with expression of HER2/neu oncogenes.
AB  - Since overexpression of HER2/neu oncogenes in breast cancer cells is associated
      with resistance to the cytotoxic effect of tumor necrosis factor (TNF), we
      investigated whether this correlation also existed for ovarian cancer targets.
      Nine continuously cultured human ovarian cancer lines were studied and compared
      to 3 breast cancer lines. Three of the ovarian and 1 breast cancer line
      demonstrated amplified HER2/neu genes by Southern analysis, increased HER2/neu
      RNA by Northern analysis, and marked immunoperoxidase staining for HER2/neu
      protein. The other 8 lines contained unamplified genes and undetectable RNA and
      protein. All 4 overexpressed lines were relatively resistant to the cytotoxic
      effects of TNF. Interestingly, they were also resistant to lymphokine-activated
      killer cells. In contrast, 7 of 8 nonexpressed lines showed sensitivity to TNF
      and all 8 were sensitive to lymphokine-activated killer cells. There was no
      difference in sensitivity to lysis by hydrogen peroxide or peptide defensins
      between over- and nonexpressed lines. These data indicate that expression of
      HER2/neu oncogenes may impart a proliferative advantage in tumor cells due to
      induction of resistance to several different cytotoxic mechanisms.

PMID- 1977520
TI  - Sympathomimetic amines and cardiac arrhythmias.
AB  - STUDY OBJECTIVE: The aim was to investigate the arrhythmogenic properties of
      several sympathomimetic amines and their antagonism by adrenergic blocking drugs.
      DESIGN: Arrhythmia was induced by the investigated drugs, injected intravenously:
      adrenaline (ADR); noradrenaline (NA); phenylephrine (PE); isoprenaline (IP);
      terbutaline (Tb) and salbutamol (Sb). ADR and PE were also tested for their
      arrhythmogenic properties after the administration of the adrenergic antagonists
      propranolol, phentolamine, or both. The dose required to induce arrhythmia and
      the proportion of animals that developed arrhythmia at a given dose were
      recorded. SUBJECTS: 63 anaesthetised cats of either sex, weight 2.0-4.3 kg, were
      used. MEASUREMENTS AND RESULTS: The electrocardiogram was recorded continuously.
      The arrhythmogenic potency sequence (expressed as arrhythmogenic dose, AD50 in
      micrograms) was: ADR 16; NA 24; PE 75; IP 133; Tb 500; Sb greater than 1000. The
      arrhythmogenic efficacy (in %) was: ADR 97; NA 91; PE 90; IP 82; Tb 50; and Sb 0.
      Propranolol and phentolamine were both effective in reducing the arrhythmogenic
      effects of ADR and PE. However, their combined administration was most effective
      and abolished the arrhythmias. CONCLUSIONS: Arrhythmogenicity is a property of
      sympathomimetic amines with either alpha or beta adrenergic effects, but
      simultaneous activation of both types of receptors is required for maximal
      manifestations. Similarly, antagonism at both sites is necessary in order to
      abolish arrhythmias induced by sympathomimetic amines completely.

PMID- 1977521
TI  - [The cohort study on HFRSV antibody variation in normal population of an epidemic
      area].
AB  - We randomly selected 2,796 persons in an epidemic area of HFRS in Anhui province
      for serological study from April to December in 1988. The results showed that the
      antibody prevalence rates were 7.3%, 10% and 14% respectively in April, September
      and December. Their GMT were 1.30, 1.42 and 1.73 respectively. Indoor rodent
      density and HFRSV carrying rate were respectively 7.8%, 6.4% in April, 9.4%, 8.8%
      in September, and 7.5%, 8.2% in December. Outdoor rodent density and HFRSV
      carrying rate were respectively 10.0%, 6.8% in April, 29.5%, 12.2% in September,
      and 10.8%, 11.0% in December. The positive seroconversion rate was 6.0% and
      negative seroconversion rate was 18.0%. The ratio of clinical infection to
      subclinical infection was 1:26. It is conclude that subclinical infection is
      dominant in HFRS infection, outdoor rodent density and their HFRSV carrying rate
      are the main factors for the infection in this HFRS endemic area.

PMID- 1977522
TI  - Crystal structure of an engrailed homeodomain-DNA complex at 2.8 A resolution: a
      framework for understanding homeodomain-DNA interactions.
AB  - The crystal structure of a complex containing the engrailed homeodomain and a
      duplex DNA site has been determined at 2.8 A resolution and refined to a
      crystallographic R factor of 24.4%. In this complex, two separate regions of the
      61 amino acid polypeptide contact a TAAT subsite. An N-terminal arm fits into the
      minor groove, and the side chains of Arg-3 and Arg-5 make contacts near the 5'
      end of this "core consensus" binding site. An alpha helix fits into the major
      groove, and the side chains of IIe-47 and Asn-51 contact base pairs near the 3'
      end of the TAAT site. This "recognition helix" is part of a structurally
      conserved helix-turn-helix unit, but these helices are longer than the
      corresponding helices in the lambda repressor, and the relationship between the
      helix-turn-helix unit and the DNA is significantly different.

PMID- 1977523
TI  - Transgenetic studies implicate interactions between homologous PrP isoforms in
      scrapie prion replication.
AB  - Transgenic (Tg) mice expressing both Syrian hamster (Ha) and mouse (Mo) prion
      protein (PrP) genes were used to probe the mechanism of scrapie prion
      replication. Four Tg lines expressing HaPrP exhibited distinct incubation times
      ranging from 48 to 277 days, which correlated inversely with HaPrP mRNA and
      HaPrPC. Bioassays of Tg brain extracts showed that the prion inoculum dictates
      which prions are synthesized de novo. Tg mice inoculated with Ha prions had
      approximately 10(9) ID50 units of Ha prions per gram of brain and less than 10
      units of Mo prions. Conversely, Tg mice inoculated with Mo prions synthesized Mo
      prions but not Ha prions. Similarly, Tg mice inoculated with Ha prions exhibited
      neuropathologic changes characteristic of hamsters with scrapie, while Mo prions
      produced changes similar to those in non-Tg mice. Our results argue that species
      specificity of scrapie prions resides in the PrP sequence and prion synthesis is
      initiated by a species-specific interaction between PrPSc in the inoculum and
      homologous PrPC.

PMID- 1977524
TI  - Regulatory role of microfilaments in the induction of T4 cell proliferation and
      interleukin 2 production.
AB  - The role of microfilaments in human T4 cell proliferation and lymphokine
      production triggered via various pathways of activation was examined by
      investigating the effects of cytochalasins on these responses. The data
      demonstrate that the effects of cytochalasins vary depending on the nature of the
      stimulus and on the concentration of the cytochalasin. Concentrations of
      cytochalasin that would be expected to bind both the low and high affinity
      binding sites (5-20 microM), that represent cytosolic and surface actin
      filaments, respectively inhibited T4 cell proliferation regardless of the
      stimulus. T4 cell proliferation stimulated by antigen-bearing APC or anti-CD3 was
      inhibited much more markedly than responses stimulated by ionomycin and PMA. In
      contrast, concentrations of cytochalasin expected to bind only high affinity
      binding sites (0.125-1 microM), represented by surface actin filaments, enhanced
      T4 cell proliferation and interleukin 2 production stimulated by mAb to CD2, CD3,
      or class I major histocompatibility complex (MHC) molecules, but not those
      induced by mAb to the T cell receptor, paraformaldehyde fixed, or viable antigen
      bearing APC, allogeneic APC, or ionomycin and PMA. The enhancing effect of
      cytochalasins on responses stimulated by cross-linking class I MHC molecules was
      studied in detail. Enhancement of T4 cell proliferation induced in this manner
      required that cytochalasin B was present between 4 and 18 hr of culture, but not
      before or after. The data demonstrate that T cell microfilaments play a number of
      roles in determining the magnitude of T cell responses induced by engaging
      specific cell surface receptors and imply that different components of the
      microfilament system exert opposing intrinsic regulatory effects on T cell
      function.

PMID- 1977525
TI  - Direct effects of serotonin, and 5-HT2, alpha 1 and H1 receptor-antagonists on
      embryonic chick skin in vitro: a morphological and functional study.
AB  - Ketanserin (K), a 5-HT2, alpha 1 and H1 receptor antagonist, at a concentration
      of 5 micrograms/ml inhibits keratinisation, but increases DNA-, collagen and
      glycosaminoglycan (GAG) synthesis in embryonic chick skin in vitro. On the other
      hand, serotonin (S) at a concentration of 10 micrograms/ml stimulates
      keratinisation and does not enhance DNA, collagen and GAG synthesis. 5 nM doses
      of ketanserin and serotonin give analogous results. The effects of other 5-HT2
      receptor antagonists (e.g. BW 501 and cinanserin) are comparable to those of K,
      whereas prazosin (an alpha 1 receptor antagonist) and pyrilamin (an H1 receptor
      antagonist) do not show any effect on embryonic chick skin in vitro.

PMID- 1977527
TI  - Direct evidence that restriction endonucleases may under estimate the degree of
      divergence between molecules.
AB  - We studied two polymorphic forms of mtDNA extracted from A. lixula eggs. In order
      to compare and to quantitate the variability, we sequenced specific regions of
      the two molecules. In this way, we obtained a precise measurement of the
      variability within two haplotypes. We also obtained a direct demonstration that
      some differences in nucleotide sequence can escape detection when restriction
      endonuclease analysis is used. Our results underline the unreliability of the use
      of restriction mapping to estimate divergence between relatively short and
      closely related DNA sequences.

PMID- 1977526
TI  - Patterns of organellar and nuclear inheritance among progeny of two
      geographically isolated strains of Volvox carteri.
AB  - Strains of Volvox carteri forma nagariensis derived from Japanese and Indian
      isolates ("J" and "I" strains, respectively) exhibited length differences (RFLPs)
      for approximately 90% of the restriction fragments detected by hybridization with
      a variety of unique-sequence, small-gene-family and repetitive-element probes,
      including heterologous probes of chloroplast and mitochondrial origin. Extensive
      post-zygotic mortality was observed among the zygotes produced by crossing J and
      I strains, suggesting some form of genetic incompatability between them. Most of
      the viable progeny exhibited recombinant patterns of nuclear inheritance and
      maternal inheritance of mitochondrial and chloroplast markers. However, many
      progeny exhibited exclusively uniparental (usually maternal, but in one case
      paternal) inheritance of both nuclear and organellar markers. Some of these non
      recombinant individuals may be derived from "parthenospores" (dormant asexual
      cells resembling zygospores). Others may be a result of "pseudogamy," in which
      one of the parental pronuclei is excluded from the zygote, followed by selective
      exclusion of both the mitochondrial and the chloroplast genomes derived from that
      same parent. When segregation patterns for 44 nuclear markers were analyzed in 90
      recombinant progeny, statistically significant, locus-specific deviations from
      expected Mendelian transmission ratios were observed for a sizeable fraction of
      all markers in both reciprocal crosses: some markers were preferentially
      transmitted by the J strain, while others were preferentially transmitted by the
      I strain. It is speculated that these transmission distortions may be related to
      the regions of inter-isolate genetic incompatibility, and may complicate the use
      of J x I crosses to establish a RFLP-based linkage map for the species.

PMID- 1977528
TI  - [Molecular basis of disease in old age and possibilities of its therapy].

PMID- 1977529
TI  - Research and development in haematology. A report on international congresses and
      visit to academic centres in Europe.
AB  - Haematology is one of the most rapidly expanding disciplines in medicine and
      nursing. As occurs in other highly specialised areas, optimum care is now largely
      of a multidisciplinary nature. In this context there are literally unlimited
      opportunities for the involvement of professional nurses and, as I have attempted
      to illustrate in this report, integration in all aspects of research and
      development and active participation in presentation of research data and
      discussion at international meetings is one direction in which fulfillment of
      academic aspirations can be achieved. It is my viewpoint, based on more than a
      decade of direct involvement in all the activities of our department in Cape Town
      that these are entirely attainable goals. There is currently, in our country, a
      concerted move afoot to develop an improved career structure for the professional
      nurse along the lines of the American clinical nurse specialist. Much of this
      experience overseas would strongly support that commitment. It was my privilege
      to enjoy the confidence of the department, university and medical school
      sufficient for me to present research data at international meetings and to be a
      welcome visitor at some of the world's premier academic and research
      institutions. That this was possible reflects the uncompromising commitment in
      Haematology to the position of the professional nurse as an integral and equal
      part of the multidisciplinary health care team.

PMID- 1977530
TI  - Recent progress in understanding apolipoprotein B.
AB  - For the past 5 years, investigators from many different laboratories have
      contributed to a greatly increased understanding of two very important lipid
      carrying proteins in plasma--apo B-100 and apo B-48. Apo B-100, an extremely
      large protein composed of 4,536 amino acids, is synthesized by the liver and is
      crucial for the assembly of triglyceride-rich VLDL particles. Apo B-100 is
      virtually the only protein of LDL, a cholesteryl ester-enriched class of
      lipoproteins that are metabolic products of VLDL. The apo B-100 of LDL serves as
      a ligand for the LDL receptor-mediated uptake of LDL particles by the liver and
      extrahepatic tissues. The LDL receptor-binding region of apo B-100 is located in
      the carboxyterminal portion of the molecule, whereas its lipid-binding regions
      appear to be broadly dispersed throughout its length. Apo B-48 contains the amino
      terminal 2,152 amino acids of apo B-100 and is produced by the intestine as a
      result of editing of a single nucleotide of the apo B mRNA, which changes the
      codon specifying apo B-100 amino acid 2,153 to a premature stop codon. Apo B-48
      has an obligatory structural role in the formation of chylomicrons; therefore,
      its synthesis is essential for absorption of dietary fats and fat-soluble
      vitamins. Both apo B-48 and apo B-100 are encoded on chromosome 2 by a single
      gene that contains 29 exons and 28 introns. An elevated level of apo B-100 in the
      plasma is a potent risk factor for developing premature atherosclerotic disease.
      In the past 3 years, many different apo B gene mutations that affect the
      concentrations of both apo B and cholesterol in the plasma have been
      characterized. A missense mutation in the codon for apo B-100 amino aid 3,500 is
      associated with hypercholesterolemia. This mutation results in poor binding of
      apo B-100 to the LDL receptor, thereby causing the cholesteryl ester-enriched LDL
      particles to accumulate in the plasma. This disorder is called familial defective
      apo B-100, and it is probably a cause of premature atherosclerotic disease.
      Familial hypobetalipoproteinemia is a condition associated with abnormally low
      levels of apo B and cholesterol; affected individuals may actually have a reduced
      risk of atherosclerotic disease.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1977532
TI  - Comparison of medical and surgical therapy for uncomplicated descending aortic
      dissection.
AB  - To guide the choice of medical versus surgical therapy for patients with
      descending (type B) aortic dissection (tear in the descending aorta without
      involvement of the ascending aorta), multivariate survival analysis was applied
      to 136 patients admitted to two medical centers between 1975 and 1988 with acute
      (n = 89) or chronic (n = 47) descending dissection: group 1, all 136 patients;
      group 2, 106 patients without rupture, pulse loss, or visceral organ compromise;
      and group 3, 56 patients from group 2 without major cardiac or renal disease (23
      surgical and 33 medical). Group 3 medical and surgical subgroups were well
      matched for baseline characteristics and were potential candidates for either
      mode of therapy. By Cox model analysis, significant predictors of mortality were
      pleural rupture, other dissection complications, increasing age, and cardiac
      disease (all p less than 0.01). Surgical versus medical therapy was not an
      independent determinant of survival in any of the three groups for acute or
      chronic dissection. Survival probabilities for all group 3 patients at 1, 5, and
      10 years were 0.94, 0.87, and 0.32 (medical) and 0.90, 0.80, and 0.50 (surgical).
      Despite the limitations of this retrospective study (including the possibility of
      undefined treatment selection biases), these data suggest that medical or early
      surgical therapy is associated with equivalent outcome in selected patients with
      uncomplicated acute or chronic descending aortic dissection.

PMID- 1977531
TI  - Ten-year follow-up of quality of life in patients randomized to receive medical
      therapy or coronary artery bypass graft surgery. The Coronary Artery Surgery
      Study (CASS)
AB  - Quality of life indexes were assessed in 780 patients 10 years after
      randomization to medical therapy (n = 390) or coronary artery bypass graft
      surgery (n = 390) in the Coronary Artery Surgery Study. At 10 years, mortality
      was 21.8% in the medical group and 19.2% in the surgical group (p = NS), and 144
      (37%) of the medical group had undergone surgery because of increasing chest
      pain. At study entry, 22% of medical and surgical patients were angina free; at 1
      and 5 years after entry, the frequency of asymptomatic patients was 66% and 63%
      in the surgical group and 30% and 38% in the medical group. However, by 10 years
      after entry, the proportion of patients free of angina had fallen to 47% in the
      surgical group and to 42% in the medical group. Activity limitation and use of
      beta-blockers and long-acting nitrates were less in the surgical than the medical
      group at 1 and 5 years after entry but little different from the medical group at
      10 years after entry. Throughout follow-up, recreational status, employment
      status, frequency of heart failure, use of other medications, and hospitalization
      frequency were similar between the two groups. Thus, indexes of quality of life
      such as angina relief, increased activity, and reduction in use of antianginal
      medications initially appear superior in patients with stable manifestations of
      ischemic heart disease assigned to surgery, but by 10 years after entry, these
      advantages are much less apparent. Although the observed similarities of the
      medically and surgically assigned groups at 10 years reflect return of symptoms
      in the surgical group to some extent, a more important explanation is the
      performance of late surgery in a large proportion of the medically assigned
      patients, rendering them asymptomatic.

PMID- 1977533
TI  - Use of nucleic acid probes in genetic tests.
AB  - Advances in molecular genetics have led to the development of clinical assays for
      several genetic diseases. Two general testing approaches are available: direct
      detection of the genetic mutation or indirect detection using DNA markers close
      to, or within, the defective gene. Direct testing at the nucleic acid level is
      available for diseases in which the basic defect is well characterized, such as
      sickle cell anemia. Several methods are available for detection of the point
      mutation that causes sickle cell anemia including: routine Southern blot
      analysis, allele specific oligonucleotides, and polymerase chain reaction gene
      amplification. For diseases such as cystic fibrosis, in which the basic genetic
      defect has not yet been characterized, an indirect approach is used. This
      approach relies on linkage analysis using DNA markers close to the genetic
      defect. Inheritance of the DNA marker is followed through the family. Unlike
      direct testing, the DNA marker does not detect the actual genetic defect.
      Therefore, a prediction of inheritance of the linked disease is given based on
      the risk of recombination between the disease locus and the DNA marker. An
      appreciation of the differences between the direct and indirect approaches is
      necessary to understand their attributes and their limitations.

PMID- 1977534
TI  - Applying highly polymorphic variable number of tandem repeats loci genetic
      markers to identity testing.
AB  - The detection of alleles of variable number of tandem repeats (VNTR) loci by
      restriction fragment length polymorphism analysis has become an important aspect
      of genetic characterization for identity testing. Some VNTR loci are so
      polymorphic that the analysis of three to five genetic markers could potentially
      provide unique identity. However, the more informative a genetic marker is (i.e.,
      high degree of polymorphisms), the better it is as an exculpatory tool. This
      approach currently provides the best avenue for excluding a falsely associated
      individual with a particular sample. When an analysis fails to exclude an
      individual as the source of the questioned material, a value (frequency of
      occurrence) should be placed on the VNTR profiles to assess weight to the
      inclusion in identity testing. Arbitrarily defined fixed bins were designed to
      accommodate quasi-continuous data and to provide a result that would not place an
      underestimation of the frequency of occurrence of a set of alleles attributed to
      an individual.

PMID- 1977535
TI  - Thyroxine-binding prealbumin gene polymorphism: a population study.
AB  - The human thyroxine-binding prealbumin (TBPA) gene was examined for restriction
      fragment length polymorphism (RFLP) in normal subjects and a subject with
      euthyroid hyperthyroxinaemia, due to increased thyroxine binding by TBPA, using
      16 restriction enzymes. Only Taq I and Msp I were shown to detect RFLPs. In a
      male of the normal population and one of his daughters, an additional Taq I site
      was found in the 3'-flanking region of the TBPA gene. The RFLP in a subject with
      euthyroid hyperthyroxinaemia was due to the deletion of a MspI site. All three
      subjects with RFLPs were heterozygous.

PMID- 1977536
TI  - Long-term treatment of metastatic medullary thyroid carcinoma with the
      somatostatin analogue octreotide.
AB  - Three patients with symptomatic metastatic medullary thyroid carcinoma (MTC), one
      with sporadic form and two with MEN IIa, were treated with the long-acting
      somatostatin analogue octreotide (SMS 201-995, Sandoz) for 3 to 17 months.
      Octreotide was administered subcutaneously in a starting dose of 0.6 to 1.0
      mg/day by automatic pump (Travax ASH6, Travenol). Symptoms of diarrhoea, weight
      loss and malaise improved in all patients. Maximal percentage decrease in mean
      serum calcitonin was 47, 52 and 81% of the basal values, and was observed 1-3
      months from the beginning of treatment. Likewise, carcinoembryonic antigen (CEA)
      levels initially dropped to 45, 60 and 63% of the levels before therapy. A
      continuing effect was seen in the two patients with MEN IIa after 15 and 17
      months of treatment. However, after the initial decrease, calcitonin (CT) levels
      went up again to 67 and 68% of the basal values and the dose of octreotide had to
      be increased to 1.5 mg and 2.0 mg/day. CEA also returned to 84 and 105% of the
      pretreatment titres. Response to 1.5 mg/day octreotide was lost in the patient
      with the sporadic form of disease after 3 months. Side-effects were minimal.
      Effects on tumour size could not be evaluated. These suggest that octreotide
      might be a valuable adjuvant in the long-term management of metastatic MTC.
      Tachyphylaxis may occur.

PMID- 1977537
TI  - CV205-502, a new non-ergot dopamine agonist, reduces prolactinoma size in man.
AB  - Seven patients with large prolactin-secreting pituitary adenomas were treated for
      8 weeks with once-daily doses of the new, potent, non-ergot, long-acting dopamine
      agonist CV205-502. In five patients previous treatment with bromocriptine had
      failed to control their disease or been poorly tolerated and had therefore
      ceased. In all seven patients serum prolactin levels fell over the 8-week period
      of CV205-502 treatment with the decrease ranging from 33 to 99%. Associated with
      this decline in prolactin all patients showed symptomatic improvement with two of
      the five women beginning to menstruate and the two patients with visual field
      impairment showing marked improvement. Tolerance of the drug, with doses at 8
      weeks ranging from 0.075 to 0.3 mg, was excellent with only minimal and transient
      side-effects being noted in three patients in none of whom was discontinuation of
      therapy necessary. In one patient noncompliance after 6 weeks of therapy was
      associated with a rapid return of her serum prolactin towards pretreatment
      levels. In all seven patients the clinical and biochemical improvement was
      accompanied by a marked reduction in tumour size.

PMID- 1977539
TI  - Distribution of intercellular-adhesion molecule-1 (ICAM-1) and lymphocyte
      function-associated antigen-1 (LFA-1) in epidermal tumours.

PMID- 1977538
TI  - Hemophilia B: diagnostic value of RFLP analysis in 19 of the 20 known Finnish
      families.
AB  - With the aim of determining the usefulness of RFLP analysis in carrier detection
      and prenatal diagnosis, we studied all available members including 40 patients,
      30 obligate carriers and 39 women at risk belonging to 19 out of a total of 20
      Finnish hemophilia B families. The allele frequencies of the three intragenic
      polymorphisms studied (TaqI, XmnI and DdeI) did not differ significantly from
      those reported in other Caucasian populations. A considerable degree of linkage
      disequilibrium between the three polymorphisms was observed. Carriership
      evaluated in 39 females at risk led to exclusion in 14 while carriership was
      established in 5. The proportion of women who by pedigree analysis had a
      carriership risk between 10% and 90% could be reduced from 97% to 51% by RFLP
      analysis. Prenatal diagnosis using an intragenic polymorphism could potentially
      be offered to 69% of hemophilia carriers. DNAs from 19 unrelated patients were
      screened for mutations using a full-length cDNA probe, but no abnormal
      hybridization patterns were observed. Our results indicate that RFLP segregation
      analysis provides a useful method of carrier detection and prenatal diagnosis in
      hemophilia B.

PMID- 1977540
TI  - Urinary excretion of albumin and enzymes in non-insulin-dependent Chinese
      diabetics.
AB  - Urine albumin (Alb), total protein (TP) and creatinine (Cr) concentrations and
      the activities of N-acetyl-beta-D-glucosaminidase (NAG), alanine aminopeptidase
      (AAP) and gamma-glutamyl transpeptidase (GGT) were measured in untimed random
      urine samples from 157 non-insulin-dependent (NIDDM) diabetic subjects and 54
      healthy subjects. In NIDDM subjects the excretions of TP, Alb, NAG, AAP, GGT
      (expressed in relation to creatinine) were significantly higher and were abnormal
      in 59.9%, 68.8%, 47.2%, 41.4% and 13.4% of the subjects, respectively. However,
      24.5%, 22.4% and 6.1% of NIDDM subjects with normal Alb/Cr ratio had abnormal
      excretion of NAG, AAP and GGT, respectively. Alb/Cr ratio was greater than 26.8
      mg/mmol (considered to be equivalent to albumin excretion of 250 mg/24 h) in
      14.6% and between 2.5-26.8 mg/mmol (equivalent to albumin excretion rates of 20
      250 mg/24 h) in 54.1% of subjects. In those diabetic subjects with clinical
      retinopathy only Alb/Cr ratio was higher. Arterial blood pressure was
      significantly correlated with Alb/Cr (r = 0.365) and NAG/Cr (r = 0.204). We
      conclude that prevalence of abnormal Alb/Cr is relatively common among Chinese
      NIDDM subjects.

PMID- 1977541
TI  - The latissimus dorsi musculocutaneous flap for extremity reconstruction in
      orthopedic surgery.
AB  - The latissimus dorsi was transferred as a pedicle flap in ten patients and as a
      free vascular flap in ten others for extremity reconstruction. Group I comprised
      ten patients in whom the transfer was used solely to cover a skin or soft-tissue
      defect. Although there was partial necrosis of the transferred skin in one
      patient, the remaining nine patients obtained complete coverage without further
      reconstructive surgery. Group II comprised five patients in whom transfer of the
      latissimus dorsi was performed for active flexion or extension of the elbow or
      for abduction of the shoulder. Postoperatively, muscle strength obtained was
      classified from Grades 0 to 5 according to the muscle testing method. Three
      patients obtained muscle strength of Grade 3, while two obtained Grade 2. Group
      III comprised five patients who had brachial plexus palsy after high-dose
      irradiation. Coverage of the skin and soft tissue was performed after neurolysis
      of the brachial plexus palsy to free the tissue bed of scarred tissue.
      Postoperatively, sensory and motor disturbances were alleviated in four of five
      patients.

PMID- 1977542
TI  - The effect of continuous epidural analgesia on postoperative pain,
      rehabilitation, and duration of hospitalization in total knee arthroplasty.
AB  - Efficacies of three alternate methods of postoperative analgesia were studied in
      156 patients who had total knee arthroplasty (TKA). Forty-two of these patients
      received parenteral meperidine hydrochloride or morphine (Group 1), 58 patients
      received periodic epidural injections of morphine (Group 2), and 56 patients
      received continuous epidural infusions of bupivacaine hydrochloride and Duramorph
      (Group 3). The postoperative course of all patients was documented in terms of
      the incidence and severity of pain, range of joint motion, duration of
      hospitalization, and occurrence of complications. Although epidural analgesia
      increased the cost and duration of the operation, good-to-excellent pain relief
      was attained in 86% (Group 2) and 88% (Group 3) of cases with epidural analgesia
      compared with 61% of patients (Group 1) receiving conventional analgesia.
      Moreover, 67% of patients in Group 1 experienced frequent episodes of moderate-to
      severe postoperative pain in contrast to 40% of patients in Group 2 and only 10%
      of patients in Group 3. As a result of diminished pain, greater joint motion was
      obtained within the first 72 hours in Groups 2 and 3. They also had shorter
      hospitalization (9.6 days versus 11.2 days for Group 1 and 10.8 days for Group
      2). However, the use of epidural analgesia did not reduce the incidence of
      complications, including nausea. Continuous infusion of epidural bupivacaine and
      Duramorph provided good-to-excellent control of postoperative pain after TKA.
      However, better analgesics are needed to reduce the high incidence of side
      effects associated with various treatment methods.

PMID- 1977543
TI  - Effect of antipyrine and phenobarbital on renal gamma-glutamyltransferase
      excretion in human urine.
AB  - Serum gamma-glutamyltransferase is used as a marker of hepatic enzyme induction.
      The kidney contains high activities of gamma-glutamyltransferase in the brush
      border membrane of the proximal tubule, from which it is released into urine.
      This study investigated the effect of phenobarbital and antipyrine, two inducers
      of hepatic monoxygenases and gamma-glutamyltransferase, on the urinary excretion
      of renal gamma-glutamyltransferase. Three groups (n = 6) of healthy male
      volunteers received 100 mg phenobarbital for 7 and 14 days and 1200 mg antipyrine
      for 7 days, respectively. Antipyrine and phenobarbital increased antipyrine
      elimination, serum gamma-glutamyltransferase, and the urinary excretion of renal
      gamma-glutamyltransferase, whereas urinary beta-N-acetylglucosaminidase, beta
      glucuronidase, and total protein and glucose excretion were unchanged. No
      correlation was found between serum and urinary gamma-glutamyltransferase or both
      enzymes and antipyrine elimination. Increases in antipyrine elimination were
      positively correlated to increases in serum, but not urinary gamma
      glutamyltransferase. The findings suggest that antipyrine and phenobarbital
      increase urinary gamma-glutamyltransferase excretion. However, the increase in
      urinary gamma-glutamyltransferase does not reflect the magnitude of hepatic
      enzyme induction.

PMID- 1977544
TI  - Pathophysiologic basis for schizophrenia and the efficacy of antipsychotics.
AB  - Current concepts of schizophrenia and its treatment are discussed. Schizophrenia
      entails negative symptoms, such as behavioral and cognitive deficits, attributed
      to loss of normal functions, and positive, or florid, symptoms that originate
      from the disturbed function of the remainder of the brain. Schizophrenia type I
      has positive symptoms predominating, and schizophrenia type II has negative
      symptoms predominating. Many atypical antipsychotics are now in Phase II and
      Phase III development; the prototype, clozapine, is now available. These agents
      challenge traditional views about drug treatment in schizophrenia. Schizophrenia
      may be explained by a persistent impairment in one or more neurotransmitter or
      neuromodulatory regulatory mechanisms, resulting in unstable or erratic
      neurotransmission. A more complex conceptualization of the role of the
      dopaminergic system makes it possible to understand the lack of biochemical
      tolerance to the therapeutic effects of antipsychotics, the varied time to onset
      of effects and prevalence of extrapyramidal symptoms, and the differences in
      efficacy within and among patients. Drug selection on the basis of patient
      specific biological markers and neuropsychological function might expedite
      treatment responses. Drug therapy should augment homeostatic mechanisms and
      restore appropriate dopaminergic responses to physiological stimuli. Atypical
      antipsychotics may act by stabilizing presynaptic activity at a new set point,
      activating prefrontal dopaminergic systems and inhibiting mesolimbic systems, or
      exerting pharmacologic or functional effects on other neurotransmitter and
      neuropeptidergic systems. The traditional view that schizophrenia is simply a
      manifestation of dopaminergic overactivity is inadequate. New investigative
      techniques and the study of atypical antipsychotics suggest that a dysregulation
      hypothesis may be more consistent with the complexities of schizophrenia.

PMID- 1977545
TI  - Information technology for diabetes care in Europe: the EURODIABETA initiative.
AB  - The EURODIABETA project is a European Community supported project to examine the
      feasibility of applying information technology to improve health care in the
      field of chronic disease using diabetes as an example. In April 1990 physicians
      and information scientists from all over Europe came together and examined the
      potential of the project in a series of workshops. As a result physicians were
      convinced of the applicability of a modelling process to describe health care
      delivery and recommended that the project be continued. They further reviewed a
      data set conceived to allow description of the status of a person with diabetes
      and concluded that it was possible to review and explain diabetes care with this
      tool.

PMID- 1977546
TI  - Tissue distribution of lipogenesis in vivo in the common murre (Uria aalge) and
      the domestic chicken (Gallus domesticus).
AB  - 1. Total body lipogenesis was similar in the murre and the chicken. 2. The liver
      contributes 10.4% to whole body lipogenesis in fed murres when measured in vivo
      using 3H2O. 3. The liver contributes 28.0% to whole body lipogenesis in the fed
      chicken. 4. The lower contribution of the liver in the murre may be a consequence
      of the high fat diet of the murre relative to the chicken.

PMID- 1977547
TI  - Heavy metal concentrations in humans.

PMID- 1977548
TI  - Changes in the phospholipid content in the left heart ventricle of male mice
      during repeated administration of isoprenaline.
AB  - 1. Male mice were injected 5 mg/kg isoprenaline (IPRO) daily and the heart
      weight, dry weight and phospholipid content in the left ventricle determined 24
      hr after the last injection on days 1, 3, 5 and 10. 2. The phospholipid content
      sinks during the experiment, but the onset of the change is different in
      different phospholipids: for diphosphatidylglycerol it is clearly significant
      after 3 days, for phosphatidylcholine and phosphatidylethanolamine after 5 days
      and for sphingomyelin after 10 days; the relative amplitude of the change in this
      latter phospholipid was greatest of all. 3. If IPRO is given for 3 days and
      physiological saline for next 7 days, the content of some phospholipids (PE, SM
      and PG) continued to decrease. This suggests an important delayed effect of IPRO
      action.

PMID- 1977549
TI  - The cardiac effects of parathyroid hormone in the tiger frog, Rana tigrina.
AB  - 1. The cardiac effects of the N-terminal (1-34) peptide fragment of bovine
      parathyroid hormone [bPTH-(1-34)] on isolated atria were examined in the frog,
      Rana tigrina. 2. bPTH-(1-34) produced dose-related inotropic response but no
      chronotropic response. This inotropic response varied at different times of the
      year. 3. The inotropic effect of bPTH-(1-34) was attenuated in the presence of
      verapamil and imidazole. 4. The mechanism of action of bPTH-(1-34) is probably a
      stimulation of calcium influx directly or indirectly via cAMP production.

PMID- 1977550
TI  - Effects of ingested crude oil on thyroid hormones and on the mixed function
      oxidase system in ducks.
AB  - 1. Ingestion of Statfjord A crude oil from the North Sea has no apparent effect
      on the metabolic rate of ducks (Jenssen, 1989). This may be because this
      particular oil does not affect plasma concentrations of thyroid hormones and
      enzyme activities in the mixed function oxidase (MFO) system of ducks. 2. To test
      this hypothesis, plasma concentrations of thyroid hormones (thyroxine and
      triiodothyronine), and levels of hepatic cytochrome P-450 and enzyme activities
      (NADPH cytochrome C reductase and GSH-S-transferase) in the MFO system were
      measured in domestic ducks (Anas platyrhynchos) which had ingested this crude
      oil. 3. Daily oral of 5 ml crude oil per kg body weight for 6 consecutive days
      resulted in a 53% increase in plasma triiodothyronine concentration and a 56%
      increase in the hepatic cytochrome P-450 level. The changes in these parameters
      were apparently not sufficient to cause any rise in metabolic heat production. 4.
      This apparent contradiction is probably because activation of the MFO-system is
      energetically inexpensive. Also, possible metabolic effects caused by increased
      plasma-triiodothyronine concentration and activation of the MFO-system may have
      been masked by an inhibitory effect of the crude oil on mitochondrial
      electrontransport and coupled phosphorylation.

PMID- 1977552
TI  - Tyramine antagonizes proctolin-induced contraction of the isolated foregut of the
      locust Schistocerca gregaria by an interaction with octopamine2 receptors.
AB  - 1. Octopamine (OA) (10(-7)-10(-5) M) relaxed isolated foreguts. Tyramine mimicked
      the effects of OA but was 64x less potent. 2. Proctolin (10(-8) M to 10(-6) M)
      induced contraction of isolated foreguts was antagonised non competitively by
      tyramine. 3. Mianserin (10(-6) M) was a non competitive antagonist of relaxation
      caused by tyramine but was without effect on proctolin induced contraction. 4.
      Caffeine (1 microM and 2 microM) caused non competitive inhibition of proctolin
      induced tissue contraction. 5. It is concluded that tyramine antagonises
      proctolin-induced contraction of the foregut by activating an adenylate cyclase
      linked OA2 receptor.

PMID- 1977551
TI  - A membrane associated glutamate binding protein from Caenorhabditis elegans and
      Haemonchus contortus.
AB  - 1. A glutamate binding protein has been identified in membrane preparations from
      the free living nematode, Caenorhabditis elegans, and from the parasitic
      nematode, Haemonchus contortus. 2. This putative glutamate receptor was
      solubilized with 30 mM octyl-B-glucoside and partially purified by anion exchange
      and gel filtration chromatography. 3. An 80-fold purification with recovery of
      75% of the glutamate binding activity was achieved. 4. The soluble C. elegans
      binding protein displayed a Kd for glutamate of 0.1 microM, in close agreement
      with the findings for the membrane associated binding protein. 5. Quisqualate was
      capable of displacing glutamate from the soluble C. elegans receptor, again in
      agreement with previous findings for the membrane bound receptor. 6. The fact
      that a parasitic nematode, Haemonchus contortus, also possesses this putative
      glutamate receptor, strengthens the case for using C. elegans as a model system
      for the study of parasitic nematode neuromuscular physiology.

PMID- 1977553
TI  - Effects of Bacillus thuringiensis delta-endotoxin on the permeability of brush
      border membrane vesicles from tobacco hornworm (Manduca sexta) midgut.
AB  - 1. The effect of two recombinant Bacillus thuringiensis delta-endotoxins on brush
      border membrane vesicles of Manduca sexta midgut was investigated using an in
      vitro assay system, based on ion-amino acid cotransport. 2. A CryIA(b)-toxin
      provoked an increase in the permeability of the vesicles. 3. A CryIB-toxin, not
      toxic to M. sexta larvae in vivo, had no effect in our assay. 4. In contrast to
      earlier reports, the increase in permeability was found to be neither selective
      for K+ nor specifically inhibited by Ca2+ or Ba2+. 5. Our data support the
      hypothesis that B. thuringiensis delta-endotoxins create non-specific pores.

PMID- 1977554
TI  - Electrophysiological and pharmacological properties of single spinal neurons
      isolated from adult bullfrogs.
AB  - 1. We developed an isolated spinal cell preparation from adult bullfrogs. 2. The
      average resting membrane potential was -60 mV, and an action potential was
      activated by positive current injection. 3. The cells retained their tetrodotoxin
      sensitive Na+ channels and at least two kinetically different types of K+
      channel. 4. Under K(+)-free conditions, responses to GABA were blocked by
      bicuculline while responses to glycine, taurine or beta-alanine were blocked by
      strychnine. 5. The potency of excitatory amino acids decreased in the order:
      kainic acid greater than glutamate greater than NMDA. 6. These studies
      demonstrated that the isolated cells are applicable for electrophysiological and
      pharmacological investigations.

PMID- 1977555
TI  - Discriminative uptake of metals by the liver and its relation to induction of
      metallothionein by cadmium, copper and zinc.
AB  - 1. Disappearance from plasma and uptake by the liver of cadmium (Cd), copper (Cu)
      and zinc (Zn) were examined with a view to studying the biological discrimination
      between essential and non-essential heavy metals. 2. Cd injected intravenously at
      a single dose of 0.8 mg/kg body wt disappeared from rat plasma rapidly within
      about 10 min, while Cu and Zn injected at the same dose disappeared slowly in
      plasma and decreased to the control level after about 3 hr. 3. Uptake of Cd by
      the liver corresponded well with the rapid disappearance from plasma, while Cu
      and Zn accumulated slowly in the liver and their concentrations started to
      increase after their plasma concentrations had decreased. 4. Metallothionein was
      induced in the liver at a similar time course for the three metals, suggesting
      the presence of discriminative uptake processes by the liver with similar or the
      same detoxification mechanisms through induction of metallothionein.

PMID- 1977556
TI  - Effects of pretreatment with cadmium on the discriminative uptake of subsequent
      cadmium, copper or zinc by the liver.
AB  - 1. Effects of pretreatment with cadmium (Cd) on the uptake by the liver of
      subsequent Cd, copper (Cu) and zinc (Zn) were examined at two different time
      intervals to elucidate the biological discrimination mechanism among metals of
      similar chemical properties. 2. Pretreatment with 0.3 mg Cd/kg body wt 6 hr but
      not 24 hr before a subsequent dose of 0.8 mg metal/kg body wt enhanced the
      disappearance rate from plasma and accumulation rate in the liver of Cu (and Zn)
      but not of Cd. 3. Synthesis of metallothionein was induced with different time
      courses depending on the time interval between the pretreatment and subsequent
      treatment, which coincided with the accumulation curves for Cu (and Zn) but not
      for Cd. 4. Although uptake of Cd was not enhanced by any pretreatment,
      metallothionein synthesis was enhanced depending on the timing of pretreatment.

PMID- 1977557
TI  - Characterisation of neurotensin-immunoreactivity in porcine ileum using region
      specific radioimmunoassays and chromatographic fractionation: isolation and
      primary structure of porcine neurotensin.
AB  - 1. Neurotensin-immunoreactivity has been characterised in porcine ileum using
      region-specific radioimmunoassay coupled to chromatographic fractionation. 2. Two
      immunoreactive peptides were identified. 3. Peptide 1 was immunochemically,
      chromatographically and structurally identical to bovine neurotensin. 4. Peptide
      2 exhibited novel immunochemical and chromatographic characteristics and
      represents a new neurotensin-related peptide.

PMID- 1977558
TI  - A study of the necrotic actions of the venom of the wolf spider, Lycosa
      godeffroyi, on mouse skin.
AB  - 1. The venom of the wolf spider, Lycosa godeffroyi, caused cutaneous necrosis
      when injected into mice. 2. A strong inflammatory response and total loss of
      epidermal cellularity were features of this in vivo necrosis. 3. Mouse skin
      envenomated while in tissue culture showed epidermal detachment and reduced
      cellular adhesion. 4. Triprolidine and methysergide, used together, indomethacin,
      heparin and human and mouse sera all failed to inhibit the necrosis
      significantly. 5. The venom caused moderate haemolysis, complement consumption
      and inhibition of clotting, these apparently not being the main reasons for the
      necrosis. 6. Neither Atrax infensus venom nor hyaluronidase caused similar
      epithelial damage.

PMID- 1977559
TI  - Angiotensin converting enzyme inhibitor potentiated the vasorelaxant response of
      atrial natriuretic peptide in toad aortic rings.
AB  - 1. The vasorelaxant effect of synthetic atrial natriuretic peptide (ANP) on the
      vascular response to angiotensin II (A II) and norepinephrine (NE) in aortic
      rings from Bufo arenarum toad was studied. 2. Pretreatment with ANP partially
      inhibited the vascular response to A II and NE. 3. Angiotensin converting enzyme
      inhibitor (ACEI) treatment partially inhibited the contractile response of
      angiotensin I (A I) and did not affect the A II response. 4. The inhibitory
      effect of ANP on vascular response to A II and NE were potentiated by
      pretreatment with ACEI. 5. Results suggest that the angiotensin converting enzyme
      present in the vascular wall from Bufo arenarum toad may be involved in the
      metabolism of ANP.

PMID- 1977560
TI  - Esmolol for severe hypertension following repair of aortic coarctation.

PMID- 1977561
TI  - Methadone as treatment for iatrogenic narcotic dependency in pediatric intensive
      care unit patients.

PMID- 1977562
TI  - Studies on lymphokine production in lepromatous leprosy patients.
AB  - In order to evaluate whether lymphokine (LK) release is impaired in patients with
      lepromatous leprosy (LL), the production of two LKs, namely leukocyte inhibitory
      factor (LIF) and interleukin-2 (IL-2) from peripheral blood mononuclear cells of
      LL individuals was investigated. Results show that in eight patients CD4+ cells
      exhibit a reduced release of LIF, while CD8+ lymphocytes are still able to
      secrete this LK. In the remaining three patients both CD4+ and CD8+ cells
      produced LIF as do normal lymphocyte subpopulations. As far as IL-2 release is
      concerned, all patients fail to produce the above LK either using purified CD4+
      or CD8+ lymphocytes. These data emphasize additional defects in immune
      responsiveness in leprosy.

PMID- 1977563
TI  - Circadian variations of plasma somatostatin levels in healthy subjects.
AB  - The plasma levels of somatostatin-like immunoreactivity, growth hormone and
      insulin were measured using a RIA method in healthy volunteers every 4h during
      the day and every 2h at night, without waking the subjects. In the waking state
      the fluctuation of plasma somatostatin-like immunoreactivity level only occurred
      near to meal time. A marked episodic surge of plasma SLI (peak value, 127.25 +/-
      4.40 pg/ml (mean +/- ES)) was noted at 0200 in the initial period of slow wave
      sleep (SWS) 2h after the peak of GH. Insulin showed no sharp peak and its pattern
      was unrelated to other two hormones studied. A positive correlation was observed
      between SLI and GH in plasma using the mean cosinor method: the acrophase of SLI
      was at 0018 about 1h later than GH (at 2315). The acrophase of insulin occurred
      at 1525, significantly different as compared with the previous two. From these
      findings, it is concluded that SLI in peripheral plasma fluctuates with a
      significant circadian rhythm and a nychthemeral maxima as GH and that, whatever
      its source, that it is related to plasma GH and not to plasma insulin.

PMID- 1977564
TI  - [Advances in the research on antirheumatic drug: sulfasalazine].

PMID- 1977565
TI  - Innervation of bladder and bowel.
AB  - The autonomic neuromuscular junction is described and neurotransmission, co
      transmission and neuromodulation are defined, as well as the 'chemical coding' of
      sympathetic, parasympathetic, sensory-motor and intrinsic neurons in the wall of
      the bladder and bowel. A detailed description of the patterns of innervation of
      smooth muscle of the bowel, bladder and urethra and of the urethral and anal
      sphincters by intramural and extrinsic autonomic nerves is presented, and the
      functional and pharmacological features of this innervation are summarized.
      Finally, changes in the pattern of innervation and expression of co-transmitters
      and receptors in the bladder and bowel that occur during development and old age
      and following trauma, surgery and disease are discussed.

PMID- 1977567
TI  - Corticosteroid treatment reduces mast cell numbers in inflammatory bowel disease.
AB  - Mast cell degranulation in the gut causes mucus secretion, mucosal edema, and
      increased gut permeability and may be responsible for some of the symptoms and
      signs of inflammatory bowel disease. We have used a novel monoclonal antibody
      (AAI) against tryptase expressed exclusively in the granules of mast cells to
      enumerate mast cells in rectal biopsies in order to study the effect of
      inflammatory bowel disease and drug treatment upon rectal mast cell numbers.
      Rectal mast cell numbers are significantly reduced in inflammatory bowel disease
      patients taking corticosteroids (mean 4.95 cells/mm2) when compared with control
      patients (10.1, P less than 0.001) and inflammatory bowel disease patients not
      taking corticosteroids (9.7, P less than 0.001 Wilcoxon rank sum test). The
      reduction in mast cell counts was independent of the degree of inflammation or
      architectural distortion. There was a negative correlation between the dose of
      corticosteroids and mast cell count (r = 0.53, P less than 0.05 Spearman rank
      correlation), and the mast cell count was reduced within a few days of treatment
      and remained low throughout steroid therapy. Mucosal mast cell depletion may be
      an important mechanism of action of corticosteroids in inflammatory bowel
      disease.

PMID- 1977568
TI  - [The effect of cycloheximide and repeated administration of hydrocortisone on
      induction of tyrosine aminotransferase gene in the rat liver].

PMID- 1977566
TI  - Plasma neurotransmitters and cortisol in duodenal ulcer patients. Role of stress.
AB  - Levels of noradrenaline, adrenaline, dopamine, free serotonin, platelet
      serotonin, and cortisol were measured in the plasma of duodenal ulcer patients
      and controls. All subjects received antacids, and these substances were also
      measured. During relapse, all patients showed raised noradrenaline, adrenaline,
      dopamine, free serotonin, and cortisol values. In contrast, platelet serotonin
      showed very low values, which correlated negatively with all the former, except
      free serotonin. No correlations were found in parameters of the controls. After
      healing, significant reductions of noradrenaline, adrenaline, dopamine, free
      serotonin, and cortisol and significant increases of platelet serotonin values
      were observed. However, only dopamine, free serotonin, and cortisol reached
      normal values. Noradrenaline and adrenaline remained higher and platelet
      serotonin lower, both significantly more so than normals. These still-altered
      parameters showed similar correlations to those found during relapses. The
      present results demonstrate that some baseline autonomic system imbalance exists
      in patients, amplified and accentuated during relapse. We discuss the possibility
      that stress plays some role in triggering duodenal ulcer relapse.

PMID- 1977569
TI  - [The serological diagnosis of Hantaan virus infections].

PMID- 1977570
TI  - [The clinical picture and therapy of Hantaan virus infection].

PMID- 1977571
TI  - [Glomerulonephritis and hepatitis B virus infection].

PMID- 1977572
TI  - [Beta-receptor blockers in acute myocardial infarction].

PMID- 1977573
TI  - Hox-2.3 upstream sequences mediate lacZ expression in intermediate mesoderm
      derivatives of transgenic mice.
AB  - The mouse Hox-2.3 gene contains an Antp-like homeobox sequence and is expressed
      in a spatially restricted anteroposterior domain during development. To study the
      molecular basis of this differential gene regulation, we set out to characterize
      the cis-regulatory elements mediating Hox-2.3 expression during embryogenesis. We
      show that a fragment extending 1316 base pairs (bp) upstream of the transcription
      start site, thus corresponding to the Hox-2.4/Hox-2.3 intergenic sequences is
      capable of mediating luciferase gene transcription in transfected cells in vitro
      and lacZ expression in transgenic mice. The beta-galactosidase-staining pattern
      in embryos was found to be strikingly similar to the Hox-2.3 in situ
      hybridization pattern in intermediate mesoderm derivatives: high levels of both
      Hox-2.3 transcripts and beta-galactosidase activity were found in the mesonephric
      duct-derived epithelium of the meso- and metanephric kidney and associated ducts,
      from the time these structures first appeared on throughout development. The
      transgene apparently lacks sequences needed for correct Hox-2.3 expression in
      somitic and lateral plate mesoderm and in neurectoderm. These results document
      the involvement of distinct regulatory elements in Hox gene expression in subsets
      of cells with distinct developmental fate, situated at similar positions along
      the anteroposterior axis of the embryo.

PMID- 1977574
TI  - Pax2, a new murine paired-box-containing gene and its expression in the
      developing excretory system.
AB  - The murine genome contains multiple genes with protein domains homologous to the
      Drosophila paired box, present in certain segmentation genes. At least one of
      these murine paired box (Pax) genes is associated with a developmental mutation.
      This report, in conjunction with the accompanying paper, describes a second
      member of this gene family, Pax2, that is also expressed during embryogenesis.
      Two overlapping cDNA clones were isolated and sequenced. At least two forms of
      the Pax2 protein can be deduced from the cDNA sequence. In addition to the highly
      conserved paired domain, an octapeptide sequence is located downstream.
      Expression of Pax2 is primarily restricted to the developing embryo in the
      excretory and central nervous systems. The transient nature of Pax2 expression
      during kidney organogenesis correlates with polarization and induction of
      epithelial structures and may indicate an important morphogenetic role for this
      gene.

PMID- 1977575
TI  - Spatially and temporally restricted expression of Pax2 during murine
      neurogenesis.
AB  - The expression of the murine paired-box-containing gene, Pax2, is examined in the
      developing central nervous system by in situ hybridization. Pax2 expression is
      detected along the boundaries of primary divisions of the neural tube. Initially,
      Pax2 is expressed in the ventricular zone in two compartments of cells on either
      side of the sulcus limitans and along the entire rhombencephalon and spinal cord.
      At later times, Pax2 is restricted to progeny cells that have migrated to
      specific regions of the intermediate zone. In the eye, Pax2 expression is
      restricted to the ventral half of the optic cup and stalk and later to the optic
      disc and nerve. In the ear, expression is restricted to regions of the otic
      vesicle that form neuronal components. The transient and restricted nature of
      Pax2 expression suggests that this murine segmentation gene homologue may also
      establish compartmental boundaries and contribute to the specification of
      neuronal identity, as do certain Drosophila segmentation genes.

PMID- 1977576
TI  - Expression of the neuronal surface glycoprotein Thy-1 is under post
      transcriptional control, and is spatially regulated, in the developing olfactory
      system.
AB  - Expression of the neuronal cell surface glycoprotein Thy-1 has been studied
      during the development of the olfactory bulb in mice and rats, using in situ
      hybridisation and immunohistochemistry to follow the appearance of Thy-1 mRNA and
      protein, respectively. The mRNA was first detected 4 days before birth on all
      mitral cells, the main projection neuron of the bulb, as they formed a distinct
      layer and grew dendrites. At no stage was any spatial gradient of expression of
      Thy-1 mRNA evident around the mitral cell layer. Thy-1 protein, on the other
      hand, was first detectable 2 days later on a group of mitral cells immediately
      adjacent the point of entry of the olfactory nerve. The numbers of immunoreactive
      cells spread, over the next 7 days, to include all mitral cells, those located
      rostrally and laterally in the bulb being slowest to express Thy-1 protein. Thus
      there was a spatiotemporal gradient of expression of Thy-1 protein, which was not
      apparent in the earlier general expression of its mRNA, suggesting that some
      further inductive signal was required after transcription in order to get
      effective production of protein. Analysis of the growth of the mitral cell axons
      in the lateral olfactory tract suggested this signal was related to the cessation
      of axonogenesis, as Thy-1 immunoreactivity became detectable on these axons only
      when their expression of the transient epitope detected by the G10 antibody,
      present on microtubule-associated protein (MAP)1x only during axonal growth,
      declined. For the first week after Thy-1 protein appeared on mitral cells, it was
      not distributed uniformally on their surface. Immunoreaction was relatively weak
      on the somatic surface, and the molecule appeared to be entirely excluded from
      the distal regions of its main dendrite, above the outer plexiform layer. Here
      the dendrite reaches up to the synaptic glomeruli formed with the incoming
      olfactory nerve axons. These distal regions of the dendritic shaft became
      immunoreactive only after the periglomerular cells had first begun to express Thy
      1 protein in the glomeruli. Immunolabelling of the somatic membrane then
      increased, to give the adult pattern of uniform Thy-1 labelling of the neuronal
      membrane by the end of the second postnatal week. It is suggested that some of
      the molecular features of Thy-1, and anatomical features of the main bulb, could
      interact to produce this initial restriction of Thy-1 to particular parts of the
      mitral cell surface.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1977578
TI  - Somatostatin-like immunoreactivity in pituitary intraglandular colloid of
      intermediate lobe origin.
AB  - The objective of this study was to determine the presence of somatostatin-like
      immunoreactivity (SSIR) in bovine pituitary intraglandular colloid (IGC) of
      intermediate lobe (IL) origin. Three colloid samples, sufficient to perform the
      assays, were taken from freshly slaughtered steers, freed of extraneous tissue
      and lyophilized. The pools were extracted with acetone and petroleum either and
      the extract radioimmunoassayed for the presence of SSIR. SSIR was present in two
      of the three samples assayed. We conclude SS is one of the many peptides found in
      pituitary IGC of IL origin.

PMID- 1977577
TI  - Outcome of intervention with or without low dose oral interferon alpha in thirty
      two HIV-1 seropositive patients in a referral hospital.
AB  - Thirty two critically ill patients were admitted to Kenyatta National Hospital
      with a diagnosis of HIV-1 seropositivity on both ELISA and Western Blot between
      October 1989 and January 1990. Sixteen of the patients received low dose oral
      interferon alpha while the other 16 patients received intensive supportive
      management alone. Of the 16 patients who received low dose interferon alpha, 14
      were discharged from the Hospital within 2 to 4 weeks of admission in a
      reasonable state of health while two of the patients died after 18 and 42 days
      from the time of admission. All the 16 patients who received intensive supportive
      management alone were dead within 4 weeks of entering the Hospital, their mean
      (+/- SD) stay after admission being 8.6 +/- 6.8 days. These results suggest that
      low dose oral interferon alpha may be of value in the care of critically ill HIV
      1 seropositive patients.

PMID- 1977579
TI  - Influence of food deprivation in the rat on hypothalamic expression of growth
      hormone-releasing factor and somatostatin.
AB  - Food deprivation in the rat is associated with a reduction in serum GH levels
      characterized by suppression of high amplitude GH bursts and a decrease in the
      duration of secretory episodes. The mechanism(s) mediating this response is
      unknown. The present studies were designed to evaluate the role of hypothalamic
      factors potentially responsible for abnormal GH dynamics in food-deprived rats by
      measuring hypothalamic prepro-GH-releasing factor (GRF) and preprosomatostatin
      (SRIF) mRNA and peptide levels in adult male Sprague-Dawley rats after 72 h of
      food deprivation or free access to food. Hypothalamic prepro-GRF mRNA was reduced
      80% in food-deprived rats compared to that in fed controls (P less than 0.001),
      while GRF content was unchanged. Levels of prepro-SRIF mRNA in food-deprived rats
      were similar to those in controls, as was hypothalamic SRIF content. The time
      course of hypothalamic prepro-GRF mRNA reduction was determined in groups of rats
      food-deprived for 24, 48, or 72 h and revealed a significant (30%) reduction of
      prepro-GRF mRNA (P less than 0.05 vs. fed) by 24 h, with maximal reduction (80%)
      by 48 h. Refeeding groups of animals for up to 72 h after they had been food
      deprived for 72 h resulted in restoration of prepro-GRF mRNA levels to 50% of
      control levels by 24 h (P less than 0.05 vs. fed) and a return to control values
      by 48 h. These data suggest that decreased GRF gene expression and possibly GRF
      release play a major role in the loss of pulsatile GH secretion seen in this
      model of nutrient deprivation.

PMID- 1977581
TI  - Cysteamine-induced enhancement of growth hormone-releasing factor (GRF)
      immunoreactivity in arcuate neurons: morphological evidence for putative
      somatostatin/GRF interactions within hypothalamus.
AB  - The episodic secretion of GH is regulated through the reciprocal release into the
      hypophyseal portal circulation of two hypothalamic peptides, SRIF and GRF. Recent
      physiological evidence suggests that, in addition to exerting their well
      documented opposite actions at the level of the anterior pituitary, SRIF and GRF
      may interact within the central nervous system to modulate GH secretion. The aim
      of the present study was to provide morphological evidence to support the concept
      that SRIF exerts an influence on the GRF-containing neuronal system within the
      hypothalamus. To accomplish this, we used the thiol agent cysteamine (CSH; 300
      mg/kg sc) to manipulate endogenous hypothalamic SRIF and examined its effects on
      the immunoreactivity and mRNA content of GRF-containing arcuate (ARC) neurons,
      using immunohistochemistry and semi-quantitative in situ hybridization,
      respectively. Hypothalamic SRIF content and pulsatile GH secretion were also
      monitored. CSH treatment reduced hypothalamic immunoreactive SRIF concentrations
      (to 60% of vehicle-injected control values) and severely suppressed the
      spontaneous surges of GH release (mean GH peak amplitude: 24.2 +/- 2.7 vs. 168.0
      +/- 27.8 ng/ml in H2O-injected controls; P less than 0.001). CSH treatment also
      resulted in a striking increase in the number and labeling density of GRF
      immunoreactive cells detected in the ARC nucleus. Cell counts revealed an overall
      126% increase, over controls, in the mean number of detectable GRF-positive ARC
      neurons. This increase (P less than 0.01) was apparent over all rostrocaudal
      levels of the ARC nucleus, but was most pronounced within the caudal tier.
      Administration of CSH also produced a massive qualitative increase in the
      intensity and extent of staining of GRF-positive terminal elements in the
      external zone of the median eminence. Conversely, CSH treatment resulted in a
      decline in GRF mRNA-associated signal in cells of the ARC nucleus, with this
      decline being most evident in the caudal third of the nucleus. The finding of an
      increase in GRF immunoreactivity in ARC neurons in association with a decrease in
      plasma GH, as well as with a decline in relative GRF mRNA content, suggests that
      CSH leads to an overall decrease in GRF release from the median eminence. These
      results provide morphological evidence to support the concept of a SRIF-mediated
      central influence on the GRF-containing ARC neuronal system. Such central
      regulation of GRF by SRIF may be an important mechanism in the physiological
      control of pulsatile GH secretion.

PMID- 1977580
TI  - Guanethidine-mediated destruction of ovarian sympathetic nerves disrupts ovarian
      development and function in rats.
AB  - Immunosympathectomy produced by treatment of newborn rats with antibodies to
      nerve growth factor (NGF) delays ovarian development and disrupts estrous
      cyclicity. While these alterations have been ascribed to loss of sympathetic
      neurons innervating the ovary, the treatment also causes partial loss of ovarian
      sensory innervation. The present experiments were undertaken to determine if
      selective interference with ovarian noradrenergic/sympathetic action would result
      in alterations of ovarian development similar to those caused by NGF antibodies
      (NGF Ab). We have used two approaches to disrupt catecholamine action on ovarian
      cells: 1) inhibition of beta-adrenoreceptors by local delivery of receptor
      blockers to the ovaries of juvenile rats; and 2) elimination of the sympathetic
      innervation by long term postnatal treatment with guanethidine (GD), an
      adrenergic neuron blocking agent. When GD is administered chronically it produces
      an autoimmune-mediated destruction of peripheral sympathetic nerves, without
      affecting cholinergic or sensory neurons. Of the receptor blockers tested, FM-24,
      a nonreversible antagonist, resulted in a sustained 70% decrease in available
      receptors throughout the 10-day period studied. In spite of this, the timing of
      puberty, assessed by the age at vaginal opening and first ovulation, was not
      delayed, suggesting that activation of the remaining receptors by an intact
      innervation suffices to maintain a normal noradrenergic influence. GD treatment
      initiated at the end of the first week of postnatal life and maintained for three
      weeks slowed the juvenile-peripubertal rate of body growth, delayed the time of
      vaginal opening and first ovulation, and disrupted subsequent estrous cyclicity,
      but did not affect the animals' fertility. The ovaries of GD-treated rats
      exhibited a striking loss of sympathetic (norepinephrine and neuropeptide Y)
      nerves but a normal sensory innervation (represented by fibers containing
      calcitonin gene-related peptide). The concentration of beta-adrenoreceptors in
      granulosa cells was reduced, suggesting follicular immaturity. Direct assessment
      of this inference by morphometric analysis of the ovaries revealed that
      follicular development was retarded. The progesterone and estrogen response of
      juvenile ovaries to gonadotropins in vitro were also reduced. At this time,
      circulating LH levels were slightly decreased, but neither LHRH content in the
      median eminence nor the LHRH response to prostaglandin E2 in vitro were
      affected.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1977582
TI  - Gene mapping and other tools for discovery.
AB  - Genetic mapping provides a means of understanding the molecular basis of
      inherited diseases whose biochemistry is unknown. Adequate pedigrees, informative
      genetic markers, and accurate identification of the disease phenotype are
      necessary. For dominant inheritance, mapping studies can be done in a single
      large pedigree; the larger the number of affected individuals sampled the better
      the estimate of recombination between the gene causing the disease and one or
      more nearby genetic markers. For recessive inheritance, nuclear families with
      more than one affected sibling provide the best information. The development of
      many polymorphic DNA markers on the human genome has contributed to the success
      of mapping unknown genes because, as the genome is now densely covered with
      markers, the probability is good that at least one marker will be linked to the
      disease locus in a family that is segregating a disease allele. Most genetic
      markers now in use depend upon restriction fragment length polymorphisms (RFLPs),
      which are either the result of single-base-pair substitution or the presence of a
      variable number of tandemly repeated oligonucleotide units at a locus (VNTRs).
      RFLPs can be recognized by digesting DNA with restriction enzymes and separating
      the fragments by size on an electrophoretic gel. VNTRs can vary widely among
      individuals, and they provide more linkage information than single-site
      polymorphic markers because family members are more likely to be heterozygous.
      Genetic maps of each chromosome, constructed from linkage data relating marker
      loci to one another in normal reference families, permit rational choices of
      markers for disease-mapping studies.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1977583
TI  - Expression of three plant glutamine synthetase cDNA in Escherichia coli.
      Formation of catalytically active isoenzymes, and complementation of a glnA
      mutant.
AB  - Three cDNA clones encoding the closely related glutamine synthetase (GS) alpha,
      beta and gamma polypeptides of Phaseolus vulgaris (French bean) were
      recombinantly expressed in Escherichia coli. The GS expression plasmids correctly
      synthesised the recombinant alpha, beta and gamma polypeptides which then
      assembled into catalytically active homo-octameric isoenzymes. These isoenzymes
      behaved similarly to their native homologues on ion-exchange and gel-filtration
      chromatography. Furthermore, the alpha and gamma isoenzymes complemented a
      GS(glnA)-deficient mutant, thus demonstrating their physiological activity in E.
      coli. Differences were observed between the three recombinant GS plasmids in
      their quantitative expression of the GS polypeptides and their ability to
      complement the E. coli mutant. These differences were correlated to the degree of
      solubility of the polypeptide, which was observed to be dependent on the
      temperature of expression. The production of active GS isoenzymes in E. coli
      facilitates the isolation and characterisation of the individual P. vulgaris homo
      octameric GS isoenzymes.

PMID- 1977584
TI  - Interaction of acetyl-CoA fragments with rat liver acetyl-CoA carboxylase.
AB  - The interaction of acetyl-CoA fragments with rat liver acetyl-CoA carboxylase has
      been studied. Dephosphorylated acetyl-CoA did not actually differ from acetyl-CoA
      in its substrate properties. Non-nucleotide analogues of the substrate, S
      acetylpantatheine and it's 4'-phosphate, also possess substrate properties (Vmax
      = 1.5% and 15% of the maximal rate value of acetyl-CoA carboxylation,
      respectively). The nucleotide fragment in the acetyl-CoA molecule produces a
      marked effect on the thermodynamics of the substrate-enzyme interaction, and is
      apparently involved in activation and appropriate orientation of the acetyl group
      in the active site. The better substrate properties of S-acetylpantetheine 4'
      phosphate and the inhibitory properties of pantetheine 4'-phosphate, compared to
      the unphosphorylated analogues, evidence an important role of the 5'-beta
      phosphate of 3'-phosphorylated ADP residue in acetyl-CoA binding to the enzyme.

PMID- 1977585
TI  - Yeast carbamoyl-phosphate-synthetase--aspartate-transcarbamylase multidomain
      protein is phosphorylated in vitro by cAMP-dependent protein kinase.
AB  - The first two steps of de novo pyrimidine synthesis in Saccharomyces cerevisiae
      are catalyzed by a multifunctional protein, coded by the URA2 gene and which has
      the carbamoyl-phosphate (CPSase) synthetase and aspartate transcarbamylase
      (ATCase) activities. The native enzyme purified from protease-B-deficient URA2
      transformed cells, was phosphorylated in vitro using catalytic subunits of pure
      cAMP-dependent protein kinase. After electrophoresis under denaturing conditions,
      a single 240-kDa species was found to be phosphorylated. Trypsin digestion of
      this species gave a single, very acidic phosphopeptide upon isoelectric
      focussing. Purification by HPLC followed by amino acid sequencing of this
      peptide, showed a phosphoserine at the expected consensus sequence Arg-Arg-Phe
      Ser. Knowledge of the URA2 gene sequence allowed the site to be located in the
      peptide link between dihydroorotase-like and ATCase domains. Such a location may
      explain why phosphorylation of the URA2 protein changed neither CPSase and ATCase
      activities nor their sensitivity to UTP, their common specific inhibitor.

PMID- 1977586
TI  - Exercise-induced platelet aggregation in angina and its possible prevention by
      beta 1-selective blockade.
AB  - Moderate exercise increased platelet aggregability of 12 middle-aged men with
      stable angina pectoris: the mean ADP threshold fell from 4.58 +/- 0.63 to 3.18 +/
      0.41 microM, P less than 0.01. Exercise did not, however, alter platelet
      aggregability in 12 healthy matched controls. Physical effort approximately
      doubled the plasma levels of adrenaline and noradrenaline in patients as well as
      in controls. Under the same conditions the cAMP content of platelets fell in the
      angina group from 20.86 +/- 1.86 to 17.78 +/- 1.71 pmol 10(-9) platelets, P less
      than 0.01, while there was no change in control levels. The fall of cAMP could
      account for the observed increase in platelet aggregability. We speculate that
      the increased aggregability of platelets in the exercising anginal subjects
      represents an imbalance between prostacyclin release and haemodynamic changes.
      The beta 1-selective blocker metoprolol, in usual therapeutic dosages, prevented
      the observed platelet changes probably by minimizing the haemodynamic
      disturbances and stimulating release of prostacyclin.

PMID- 1977587
TI  - Thrombolysis in practice. Satellite symposium to the XIth Congress of the
      European Society of Cardiology. 13 September, 1989, Nice, France. Proceedings.

PMID- 1977588
TI  - Re-orchiopexy: advantages and disadvantages.
AB  - Re-orchiopexy was performed in 33 boys (42 testes) in order to place an
      undescended testis in the scrotum after failure of the initial operation. Success
      was achieved in 80.9%. Seven of the 10 testes, reported to have short spermatic
      vessels at the first surgery, had no elongation of the vessels and only 1 of
      these resulted in a high scrotal location of the testis. It appears that most
      orchiopexy failures are the result of technical failures of the initial
      procedure. Standard orchiopexy with extensive mobilization of the spermatic
      vessels and testis can successfully correct most of the undescended testes.
      However, the preferred management for the intra-abdominal testis with short
      vessels may be transection of the spermatic vessels rather than a planned two
      stage technique.

PMID- 1977589
TI  - IgG heavy-chain subclass restriction of thyrotropin-binding inhibitory
      immunoglobulins in Graves' disease.
AB  - The IgG subclass composition of antibodies is an important determinant of their
      function. Thyrotropin receptor antibodies cause the hyperthyroidism of Graves'
      disease but their subclass distribution has been incompletely investigated. We
      have therefore purified IgG subclasses from Graves' sera by passage over affinity
      columns designed to deplete all but a single subclass, and then assayed those
      pure subclass fractions for their ability to displace radiolabelled thyrotropin
      from its solubilized receptor as a measure of thyrotropin receptor antibody
      activity. Sufficient activity was recovered for analysis in nine of 10 Graves'
      patients, in five of whom activity was almost completely (97-100%) restricted to
      the IgG1 subclass; in the remaining four patients the response was predominantly
      IgG1 and IgG4 with marked under-representation of the IgG2 subclass. This
      contrasts with the unrestricted subclass response, in the same fractions, for
      autoantibodies against thyroglobulin and microsomes. These results suggest that
      there may be a primary defect at the B-cell level in Graves' disease.

PMID- 1977590
TI  - Interaction of the atypical neuroleptic clozapine with 5-HT3 receptors in the
      cerebral cortex and superior cervical ganglion of the rat.
AB  - Clozapine, an atypical neuroleptic drug devoid of extrapyramidal side effects,
      was a moderately potent, competitive inhibitor of the binding of [3H]quaternised
      ICS 205-930 to 5-HT3 receptor sites in rat cortical membranes, possessing a pKi
      value of 7.0. In contrast, several other antipsychotic agents, including
      fluphenazine, alpha-flupenthixol, haloperidol, spiperone and (-)-sulpiride were
      essentially inactive. Clozapine also antagonised the 2-methyl 5-HT-induced
      depolarisation of the rat isolated superior cervical ganglion, a response known
      to be mediated via 5-HT3 receptors. Clozapine (0.1-1 microM) induced parallel
      displacements to the right of the dose-response curve to 2-methyl 5-HT in this
      tissue, possessing a pKb value of 7.3. These data suggest that the atypical
      antipsychotic profile of clozapine may be related, at least, in part to its
      ability to interact with central 5-HT3 receptor sites.

PMID- 1977591
TI  - Evidence against purines being neurotransmitters of non-adrenergic, non
      cholinergic nerves in rat duodenum.
AB  - The possible involvement of purines in the non-adrenergic non-cholinergic (NANC)
      relaxation of rat duodenum was studied using an isometric-isovolumic preparation.
      Purines (adenosine, AMP, ADP, ATP) induced a concentration-dependent,
      tetrodotoxin (TTX)-insensitive, fall in both endoluminal pressure and isometric
      tension. The relaxation induced by adenosine and by 2-chloroadenosine was
      selectively antagonized by 8-phenyltheophylline (1, 10 nM, 0.5 microM) and the
      ATP-induced relaxation was opposed by alpha, beta-methylene ATP (10 microM) and
      by reactive blue 2 (10 microM). Electrical field stimulation (EFS) caused TTX
      sensitive inhibitory effects similar to those induced by ATP. None of the
      purinergic antagonists used were capable of affecting the EFS-induced relaxation.
      Our results indicate that both P1 and P2 purinoreceptors are present in muscle of
      the rat duodenum and are not involved in the NANC relaxation.

PMID- 1977592
TI  - Effects of beta-endorphin and dynorphin A on cholinergic neurotransmission in
      canine airway smooth muscle.
AB  - To determine the effects of the opioid peptides, beta-endorphin and dynorphin A,
      on airway smooth muscle function and its possible modulation by tissue
      peptidases, we studied canine bronchial segments under isometric conditions in
      vitro. Addition of beta-endorphin or dynorphin A did not alter the resting
      tension. However, beta-endorphin (10(-6) M) but not dynorphin A decreased the
      contractile responses to electrical field stimulation (EFS, 0.5-40 Hz). This
      effect was dose-dependent and reversed by naloxone. In contrast, acetylcholine
      induced contractions were not affected by these opioids. The beta-endorphin
      induced inhibition of the contractile responses to EFS was not augmented by
      peptidase inhibitors such as thiorphan, captopril, bestatin and leupeptin. These
      results suggest that beta-endorphin prejunctionally inhibits parasympathetic
      muscle contraction, and that endogenous peptidases do not play a modulatory role
      in this effect of beta-endorphin.

PMID- 1977593
TI  - Attenuation of benzodiazepine-induced passive avoidance deficit by post-training
      administration of muscimol: interaction with the cholinergic neuronal system.
AB  - We examined the involvement of GABAergic neuronal systems in benzodiazepine
      induced passive avoidance deficit. Chlordiazepoxide impaired the passive
      avoidance response dose dependently when it was given prior to training. Post
      training administration of muscimol improved the performance of chlordiazepoxide
      pretreated mice. The effects of muscimol were antagonized completely by the GABAA
      antagonist, bicuculline, and the muscarinic acetylcholine receptor antagonist,
      scopolamine, but not by the benzodiazepine receptor antagonist, flumazenil, when
      the latter was administered immediately after training. It appears from these
      results that the GABAergic neuronal system plays an important role in the
      benzodiazepine-induced passive avoidance deficit by interacting with the
      cholinergic neuronal system.

PMID- 1977595
TI  - MK-801 potentiates dopaminergic D1 but reduces D2 responses in the 6
      hydroxydopamine model of Parkinson's disease.

PMID- 1977594
TI  - Alpha 2-adrenoceptor mechanisms in guinea-pig trachea.
AB  - In the presence of propranolol tracheal strips from guinea-pigs were markedly
      contracted by norepinephrine and clonidine but only slightly by phenylephrine.
      The contractile responses to clonidine and norepinephrine were inhibited by
      yohimbine but not by prazosin. The specific binding of [3H]p-aminoclonidine to
      the microsomal fractions from guinea-pig tracheal muscle was much greater than
      that of [125I]BE2254. These results indicate that alpha 2-adrenoceptors are the
      predominant subtype of alpha-adrenoceptor in the guinea-pig trachea. The response
      to norepinephrine was abolished by cyclooxygenase inhibitors, suggesting the
      release of excitatory prostaglandins by norepinephrine. These results raise the
      possibility that norepinephrine interacts with alpha 2-adrenoceptors and releases
      prostaglandins to contract tracheal muscle.

PMID- 1977596
TI  - Sertindole, a new neuroleptic with extreme selectivity on A10 versus A9 dopamine
      neurones in the rat.

PMID- 1977597
TI  - Benextramine: a long-lasting neuropeptide Y receptor antagonist.

PMID- 1977598
TI  - Inhibitory effects of catecholamines in the paravertebral sympathetic ganglia of
      the anesthetized dog.
AB  - alpha-Adrenoceptor agonists decreased mean arterial pressure when injected into
      the arterial blood supply of the paraspinal sympathetic ganglia of pentobarbital
      anesthetized open-chest dogs. The hypotensive response occurred concomitantly
      with selective decreases of vascular resistance in the vessels innervated by
      neurons arising from these ganglia, and both of these responses were blocked by
      the ganglionic blocking agent, hexamethonium. The hypotensive response to
      phenylephrine was selectively blocked by terazosin; alpha 1 selective agonist,
      and antagonist, respectively, while the hypotension produced by intra-arterial
      clonidine was blocked by rauwolscine; alpha 2 selective agonist and antagonist,
      respectively. Either terazosin or rauwolscine reduced the hypotension produced by
      noradrenaline or dopamine. These results demonstrated the presence of both alpha
      1- and alpha 2-adrenoceptors in the paraspinal sympathetic ganglia. Activation of
      either alpha-adrenoceptor subtype inhibited ganglionic transmission.

PMID- 1977599
TI  - Effects of the dopamine receptor agonists, fenoldopam and quinpirole, in the rat
      stomach.
AB  - The effects of the DA1-receptor agonist, fenoldopam, and the DA2-receptor
      agonist, quinpirole, were studied with the longitudinal muscle of rat gastric
      fundus and circular muscle of rat gastric corpus, as there are contrasting
      reports about the receptors involved in the inhibitory effect of dopamine in
      these tissues. Quinpirole had no effect on basal tone in the longitudinal muscle
      of the rat gastric fundus and did not inhibit the sustained contractions induced
      by electrical field stimulation or by methacholine. Fenoldopam had no effect on
      the tone increased by methacholine but slightly potentiated the electrically
      induced contraction at the highest concentrations; it concentration dependently
      (10(-7)-3 X 10(-5) M) increased the basal tone. The contractile effect of
      fenoldopam was clearly antagonized by rauwolscine 10(-6) M, yohimbine 10(-6) M
      and phentolamine 3 X 10(-6) M plus propranolol 10(-5) M. The 5-HT receptor
      antagonist, methysergide, antagonized the fenoldopam-induced contractions in a
      non-competitive way. Fenoldopam and quinpirole had no effect on contractions
      induced in the circular muscle of the rat gastric corpus by methacholine or
      electrical field stimulation. They induced some contraction at basal tone, at
      their highest concentrations. As fenoldopam and quinpirole did not mimic the
      inhibitory effect observed with dopamine in the same models, no evidence was
      found for the presence of inhibitory dopamine receptors in rat gastric muscle.
      The contractile effect of fenoldopam in the longitudinal muscle of the fundus is
      probably due to an interaction with 5-HT receptors.

PMID- 1977600
TI  - Sodium nitroprusside potentiates the depressor response to the phosphodiesterase
      inhibitor zaprinast in rats.
AB  - To determine if the presence of an activator of guanylate cyclase alters the
      depressor response to a selective inhibitor of low Km cyclic GMP (cGMP)
      phosphodiesterase (PDE), zaprinast (3-30 mg/kg) was given i.v. to conscious,
      spontaneously hypertensive rats during a steady state of i.v. infusion of sodium
      nitroprusside (15 micrograms/kg per min). Sodium nitroprusside significantly
      increased the magnitude of the depressor response to zaprinast. In contrast,
      fenoldopam (20 micrograms/kg per min), an activator of adenylate cyclase, did not
      affect the depressor response to zaprinast. Zaprinast (10 mg/kg) significantly
      decreased mean arterial pressure (MAP) in rats given an infusion of sodium
      nitroprusside, an activator of soluble guanylate cyclase, at doses of 15 and 25
      micrograms/kg per min but not at a dose of 5 micrograms/kg per min. However, in
      rats given atrial natriuretic peptide (ANP; 0.5, 1 and 2 micrograms/kg per min),
      an activator of particulate guanylate cyclase, zaprinast (10 mg/kg) did not
      affect MAP. In contrast to the potentiation of the depressor response to
      zaprinast, sodium nitroprusside (15 micrograms/kg per min) significantly
      attenuated the reductions in MAP produced by CI-930, a selective inhibitor of low
      Km cAMP PDE. It is concluded that sodium nitroprusside, but not ANP or
      fenoldopam, potentiates the depressor response to zaprinast. Furthermore, the
      potentiation of the depressor response to zaprinast is dependent upon the dose of
      sodium nitroprusside and is selective for zaprinast; the depressor response to CI
      930 is attenuated by sodium nitroprusside.

PMID- 1977602
TI  - Caged ATP potentiates guanylate cyclase activity stimulated by atrial natriuretic
      factor in rat lung membranes.
AB  - ATP increases both basal and atrial natriuretic factor (ANF)-stimulated guanylate
      cyclase activities. The present studies were designed to compare the effect of
      adenosine-5'-triphosphate, P3-1-(2-nitrophenyl)-ethyl ester (caged ATP), a
      photolabile derivative of ATP, with ATP. Caged ATP increases both basal and ANF
      stimulated enzyme activities in a concentration-dependent manner, but is more
      potent than ATP. The effect of caged ATP significantly decreases after it is
      photo-converted to ATP by UV irradiation. These observations suggest that the
      caged group introduces a hydrophobic interaction thereby facilitating guanylate
      cyclase activation.

PMID- 1977601
TI  - Developmental changes in alpha 1-adrenoceptor coupling to G-protein in bovine
      aorta.
AB  - Differences in epinephrine binding to alpha 1-adrenoceptors, epinephrine-induced
      contractile potency, susceptibility to phorbol ester (PDBu) modulation, and
      differences in membrane fluidity were studied in bovine aorta from young (3-8
      weeks) and adult or mature (6-8 years) animals. Membranes prepared from aorta of
      adult animals exhibited a two-fold higher receptor density while [3H]prazosin
      affinity was unchanged. Epinephrine displacement studies revealed both high- and
      low-affinity binding in membranes from the aortas of young animals whereas,
      preparations from adult animals exhibited only a single class of low-affinity
      sites. In low-temperature binding studies, membranes prepared from aortas of
      adult animals exhibited both high- and low-affinity agonist binding, in
      proportions about equal to those of young animals. The ability of PDBu to
      uncouple alpha 1-adrenoceptor from G-protein interaction is demonstrable in young
      but not in adult animals which raises the possibility of prior phosphorylation of
      receptors in the latter tissues. Aortas from young animals showed increased
      contractile potency to epinephrine and, in addition, were significantly more
      fluid as compared to aortas from adult animals. Alterations in the membrane
      environment or phosphorylation state of the alpha 1-adrenoceptor may thus provide
      age-dependent modulation of its function.

PMID- 1977603
TI  - Optically active benzamides as predictive tools for mapping the dopamine D2
      receptor.
AB  - Substituent variations on the pyrrolidinyl nitrogen of sulpiride, a selective D2
      dopamine antagonist, showed that in vitro and in vivo activities are concentrated
      in the (S) optical series for N-alkyl analogs and in the (R) series for N-benzyl
      analogs. To account for these unusual structure-activity relationships, a
      pharmacophoric model was built from the crystallographic structure of (
      )piquindone and extended to 14 other D2 antagonists. This model considers the
      lone pair orientation of the basic nitrogen rather than its spatial location. Two
      distinct active conformations for benzamides were defined, corresponding to the
      (S) and (R) series. An extended pharmacophore is then proposed involving four
      main anchoring areas: (i) an aromatic site Ar1, (ii) a tertiary nitrogen with its
      lone pair orthogonal to the Ar1 plane, (iii) a dipole delta 1 coplanar to the Ar1
      ring and (iv) three sites for the N-substituent, including a small hydrophobic
      pocket and two different aromatic binding sites Ar2 and Ar3. To probe the
      predictive value of this model, structures were designed and several compounds
      were synthesized and tested as inhibitors of [125I]iodo-sulpiride binding to rat
      striatal membranes and as antagonists of apomorphine-induced stereotyped behavior
      in mice.

PMID- 1977604
TI  - Taxol inhibits stimulation of cell DNA synthesis by human cytomegalovirus.
AB  - The microtubule (MT)-stabilizing drug, taxol, inhibited human cytomegalovirus
      (CMV)-initiated cell DNA synthesis by up to 100% in serum-arrested mouse embryo
      (ME) fibroblasts that were abortively infected by CMV. Taxol concentrations known
      to increase MT polymerization and to stabilize existing MTs (10 to 20
      micrograms/ml) blocked CMV-stimulated cell DNA synthesis, while taxol
      concentrations of 2.5 micrograms/ml, or less, did not. Taxol maximally inhibited
      CMV initiation of cell DNA synthesis when added 3 h after virus infection and
      inhibited this initiation by greater than 50% when added up to 12 h after CMV
      infection. Control experiments suggest that taxol specifically inhibited CMV
      stimulated cell DNA synthesis. Pretreatment of CMV stock with taxol did not
      reduce the stimulatory effect of CMV on cell DNA synthesis and taxol had no
      detectable effect on CMV-specific early protein synthesis. Moreover, taxol did
      not appear to alter thymidine pool sizes, affect cell viability, or compromise
      the DNA synthetic machinery in CMV-infected cells. Since taxol increases tubulin
      polymerization and inhibits MT disassembly, these results suggest that dynamic
      changes in MTs or in the pool of free tubulin subunits are necessary for CMV to
      stimulate cell entry into a proliferative cycle.

PMID- 1977605
TI  - Proceedings of the 1st International Symposium on Calcium, Molecular Biology and
      Aging. Siena, Italy, October 17-19, 1988.

PMID- 1977606
TI  - Intracerebral adrenal medulla grafts: a review.
AB  - This review summarizes basic and clinical research on intracerebral adrenal
      medulla grafts, emphasizing potential applications to Parkinson's disease.
      Properties of intraventricular and intraparenchymal grafts are described, and
      cell survival and functional effects are compared. It is clear that adrenal
      medulla allografts survive poorly in the parenchyma of the corpus striatum and
      better in the lateral ventricle. Nerve growth factor (NGF) may improve the
      survival of adrenal medulla grafts. In the absence of added NGF even adrenal
      medulla grafts in the ventricle survive irregularly, and the factors required for
      graft survival in the ventricle are not well understood. In the 6-hydroxydopamine
      lesioned rat model most evidence suggests, not surprisingly, that adrenal medulla
      grafts produce functional effects only when they survive. These effects may be
      related to production of catecholamines by the transplanted cells. In addition,
      adrenal medulla grafts may produce trophic effects on host brain. These effects
      are most evident in animals with MPTP-induced damage to dopaminergic systems and
      may be nonspecific, possibly related in part to the brain injury that is induced
      by graft implantation. Trophic effects may contribute to the functional effects
      of adrenal medulla grafts: For intraparenchymal grafts, trophic effects that do
      not require cell survival may contribute small functional changes, while
      additional behavioral effects may require substantial chromaffin cell survival.
      The evidence for direct dopamine-mediated effects as compared to trophic
      mechanisms of action for these grafts in animal models for Parkinson's disease is
      presented. Clinical studies of adrenal medulla grafts in human patients are
      examined and compared in detail. When inspected closely, the various clinical
      studies are in general agreement on most points, although there are differences
      in the degree of improvement found, both across different studies and individual
      patients. It is concluded that some beneficial clinical effects occur, with small
      to modest changes in most patients and substantial improvement in a minority of
      patients. There also seem to be larger or more consistent changes in durations of
      "on" and "off" times in L-dihydroxyphenylalanine-treated patients. There are
      substantial side effects, and it is not clear that the clinical changes are
      sufficient to justify performing adrenal medulla transplantation in human
      patients as a routine procedure.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1977607
TI  - Extensive survival of chromaffin cells in adrenal medulla "ribbon" grafts in the
      monkey neostriatum.
AB  - Experimental neurosurgical implantation of adrenal medulla tissue has been
      performed as a treatment for Parkinson's disease at several medical centers
      around the world, and similar techniques have been applied in a small number of
      nonhuman primates. None of these efforts to date has resulted in histological
      evidence of significant graft survival, and behavioral improvement in patients
      has been modest at best. The present series of experiments, however, has led to a
      novel and effective technique for stereotaxic implantation of long, narrow
      "ribbons" of autologous adrenal tissue in the monkey caudate and putamen nuclei.
      The survival and enzymatic activity of large portions of intact grafted ribbons
      have been demonstrated by tyrosine hydroxylase immunohistochemistry. Efforts
      based on other grafting techniques resulted in poor or mediocre survival,
      reminiscent of previously published results. Successful grafts, on the contrary,
      were morphologically similar to intact adrenal medulla tissue, except that
      neuronal processes were observed emanating from some of the transplanted cells.
      The success of the present technique, which minimally distorts or traumatizes
      adrenal and brain tissue, may be due primarily to the rapid establishment of a
      blood supply by anastomosis with host vessels. In most monkeys, nerve growth
      factor was also administered to the lateral ventricle for the duration of the
      graft, but excellent results were also achieved in the monkey that did not
      receive such treatment. We conclude that adrenal grafts made by the present
      technique can survive and function in primates.

PMID- 1977608
TI  - Loss of striatal somatostatin neurons following prenatal methylazoxymethanol.
AB  - Prenatal administration of methylazoxymethanol acetate (MAM), which kills
      neuroblasts undergoing mitosis, was used to lesion striatal somatostatin neurons.
      Previous [3H]thymidine autoradiographic studies had indicated that striatal
      somatostatin neurons undergo their final mitotic division at Gestational Days (G)
      15 and 16. Therefore, pregnant Sprague-Dawley rats received an intraperitoneal
      injection of MAM (25 mg/kg) on G15. Neurochemical and histological examination of
      the mature offspring indicated the loss of half the striatal aspiny interneurons
      in which somatostatin, neuropeptide Y, and NADPH diaphorase coexist, with
      relative sparing of the cholinergic interneurons and medium spiny projection
      cells. This prenatal MAM treatment was without apparent effect on the patch
      matrix organization of the striatum.

PMID- 1977609
TI  - Ischemic damage in the striatum of adult gerbils: relative sparing of
      somatostatinergic and cholinergic interneurons contrasts with loss of efferent
      neurons.
AB  - The pattern of ischemia-induced cell death was examined with histochemical
      methods in the striatum of adult gerbils 4 and 7 days after transient forebrain
      ischemia. The results showed a massive loss of immunoreactivity to enkephalin and
      tachykinins, peptides present in striatal efferent neurons. In contrast, neurons
      expressing acetylcholinesterase activity, or choline acetyltransferase
      immunoreactivity, as well as neurons immunoreactive for somatostatin, were
      relatively preserved in areas of severe neuronal loss. The selective
      vulnerability of subpopulations of striatal neurons to transient ischemia in the
      adult is similar to that observed in the neonate and after local injections of
      agonists of N-methyl-D-aspartate receptors, but not of agonists of other
      glutamate receptor subtypes. It also presents striking similarities to the
      pattern of neuronal death observed in Huntington's disease. The results further
      support a role for overstimulation of a subtype of excitatory amino acid receptor
      in ischemia-induced cell death and show that the selective sparing of
      subpopulations of striatal interneurons after ischemic injury is not related to
      immaturity of these neurons but also occurs in the adult.

PMID- 1977610
TI  - Mitochondrial DNA variation in social wasps (Hymenoptera, Vespidae).
AB  - Patterns of restriction fragment length polymorphisms (RFLP) of European Vespinae
      were more similar within genera than between them. Distance trees were
      constructed that support the hypothesis of monophyly of the genera Vespula and
      Dolichovespula. Within the genus Vespula, V. germanica was more closely related
      to V. rufa than to V. vulgaris. The position of the genus Vespa remained
      uncertain due to the precision limits of the RFLP technique.

PMID- 1977611
TI  - Immunological definition of acute promyelocytic leukemia (FAB M3): a study of 39
      cases.
AB  - Acute promyelocytic leukemia (FAB-M3) is a distinct entity among acute non
      lymphoid leukemias (ANLL) with peculiar morphological, biological, clinical and
      prognostic features. An atypical form of M3 (M3v) could be confused with other
      FAB ANLL and therefore the diagnosis of this variant requires ultrastructural
      analysis and/or cytogenetic study and/or selective gene rearrangement studies.
      The immunological phenotype of blast cells in 39 APL patients was studied at
      diagnosis. The diagnosis of M3 FAB type was ascertained in 32 and the diagnosis
      of M3v in 7 cases. Using a large series of monoclonal antibodies (mAb), the APL
      blast cells were B and T cell antigens-negative, HLA-DR constantly negative, CD13
      and/or CD33-positive, CD9-positive. Among ANLL this phenotype seems to be
      closely related to APL both in M3 type and M3v subtype. Because the diagnosis of
      APL (M3 or M3v) is important in order to establish the specific therapeutic
      approach, the discriminant capacity of the immunological typing to identify M3
      and mainly M3v (hypogranular) could be determinant for a "quick" diagnosis.

PMID- 1977612
TI  - Immunogenotyping with antigen receptor gene probes as a diagnostic tool in
      childhood acute lymphoblastic leukaemia.
AB  - 13 cases of childhood acute lymphoblastic leukaemia (ALL) were studied combining
      cell surface marker analysis with immunogenotyping by Southern blot hybridisation
      with a panel of antigen receptor gene probes. The immunophenotypes were
      unequivocal: 7 patients had B-phenotype and 6 patients T-phenotype ALL. In
      several patients immunogenotypes were not fully consistent with the respective
      phenotypes. For example, 2 B-cell precursor ALL had rearranged TCR beta chain
      genes and 2 T-ALL rearrangement of Ig heavy-chain genes. All cases showed clonal
      rearrangement or deletions within the TCR delta gene locus. TCR delta gene
      rearrangements might, therefore, serve as markers of clonality but not of B- or T
      lineage in immature lymphoid neoplasms. We conclude that in current diagnostic
      practice immunogenotyping is a supplement rather than an alternative to
      immunophenotyping by surface marker analysis.

PMID- 1977613
TI  - [A new substance with nootropic activity--N-5(hydroxynicotinoyl)-L-glutamic
      acid].
AB  - The psychopharmacological activity of a new compound--ONK-10--N
      5(hydroxynicotinoyl)-L-glutamic acid was studied. It was shown in experiments on
      mice and rats that the compound possesses the pronounced antiamnestic and
      antihypoxic effects, does not disturb the conditioned reflex activity and the
      orientation behavior, has no anxiolytic activity and anticonvulsant properties,
      causes no disorder of movement coordination, is low toxic. ONK-10 is superior by
      its antiamnestic and antihypoxic effects to piracetam, meclophenoxat, demanol
      aceglumate and is not inferior to aniracetam.

PMID- 1977614
TI  - [The effect of the new Soviet antihistamine and antiserotonin preparation
      bikarfen on the central nervous system].
AB  - The effect of an antiallergic (antihistaminic and antiserotonin) drug bicarphen
      on the functional state of the central nervous system (CNS) was studied. In
      experiments on animals bicarphen in contrast to dimedrol (diphenhydramine)
      exerted predominantly the activating effect on CNS (decreased the hypnotic action
      of barbamyl, enhanced the summation capacity of CNS and the activity of mice in
      the escape behavioral test, increased the bioelectrical activity of the brain and
      the activating effect of antidepressants on the EEG).

PMID- 1977615
TI  - Cloning and structure of cDNA encoding alpha-latrotoxin from black widow spider
      venom.
AB  - cDNA encoding the putative alpha-latrotoxin precursor was isolated from spider
      venom glands cDNA library and sequenced. The cDNA contained the 4203 base-pair
      open reading frame corresponding to the 156,855-Da protein composed of 1401 amino
      acids. Computer analysis of the deduced primary structure revealed the presence
      of various internal imperfect repeats mainly in its central and C-terminal
      regions.

PMID- 1977616
TI  - Generation of inositol phosphates, cytosolic Ca2+, and secretion of noradrenaline
      in PC12 cells treated with glutamate.
AB  - Glutamate transiently stimulated rat pheochromocytoma PC12 cells and caused an
      inositol trisphosphate formation and an increase in levels of Ca+ in the cytosol.
      The rank order of potency of glutamate greater than N-methyl-D-aspartate (NMDA)
      much greater than kainate = quisqualate is characteristic of an interaction with
      NMDA receptors. The effect of glutamate on inositol trisphosphate formation
      disappeared in a low Mg2+ buffer and was not blocked by DL-2-amino-5
      phosphonovalerate, an antagonist for NMDA receptors coupled to ion channels.
      Although glutamate failed to stimulate noradrenaline secretion, glutamate
      enhanced the effect of bradykinin, but not of Ca ionophore A23187, or KCl. These
      results suggest the existence of metabotropic glutamate receptors, different from
      previously reported receptors, in PC12 cells.

PMID- 1977617
TI  - Expression of the cholecystokinin gene in a human (small-cell) lung carcinoma
      cell-line.
AB  - Expression of the cholecystokinin (CCK), gastrin and enkephalin A genes were
      studied by Northern blot analysis and a library of sequence-specific
      radioimmunoassays in human cell lines. The human small-cell lung carcinoma line
      (SCLC) U-1690 expressed moderate levels of CCK mRNA as compared to the human
      neuroepithelioma cell line SK-N-MC. Neither gastrin nor (pro)enkephalin A mRNAs
      were detectable in the U-1690 cell line. In contrast, the SCLC-line H-69
      expressed Enk A but no CCK mRNA. The radioimmunoassays showed that the CCK mRNA
      transcript in the SCLC line U-1690 also is translated, and that preproCCK is
      processed into bioactive, carboxyamidated CCK peptides. Thus, the human small
      cell carcinoma cell line U-1690 is a useful model for studies of cell-specific
      CCK gene expression.

PMID- 1977618
TI  - AT repeats in barely genome.
AB  - The DNA sequence (AT)26 of barley genome has been cloned. This sequence is
      arranged in intraspecific locus and is repeated 1500 times per haploid genome.
      This fragment is not translated and can form cruciform structures in the AT
      region.

PMID- 1977619
TI  - Expression of soluble guanylyl cyclase. Catalytic activity requires two enzyme
      subunits.
AB  - Purified soluble guanylyl cyclase consists of two subunits (70 and 73 kDa) whose
      primary structures were recently determined. The availability of cDNA clones
      coding for either subunit allowed to study the question of the functional roles
      of the two subunits in expression experiments. Enzyme subunits were expressed in
      COS-7 cells by transfection with expression vectors containing the coding region
      for the 70 of 73 kDa subunit of the enzyme. No significant elevation in the
      activity of soluble guanylyl cyclase was observed in cells transfected with cDNA
      coding for one of the subunits. In contrast, transfection of cells with cDNAs
      coding for both subunits resulted in a marked increase in activity of soluble
      guanylyl cyclase. Enzyme activity was stimulated about 50-fold by sodium
      nitroprusside. The results indicate that formation of cyclic GMP by soluble
      guanylyl cyclase requires both 70 and 73 kDa subunits.

PMID- 1977620
TI  - Effect of antipsychotic drugs on the molecular action of cholera toxin in rabbit
      intestinal epithelial cells.
AB  - Antipsychotic drugs of known antidiarrhoeal and anticalmodulin activity inhibited
      the cholera-toxin-catalysed ADP-ribosylation of proteins of Mr 37,000, 40,000 and
      45,000 (thought to be regulatory components of the adenylate cyclase complex)
      that was previously shown to occur in plasma membranes from rabbit intestinal
      epithelial cells [(1989) Biochim. Biophys. Acta 1014, 289-297]. There was no
      obvious correlation between the different activities of the drugs. The drugs also
      inhibited adenylate cyclase activity, but in this case the inhibition correlated
      well with the known IC50 values of the drugs for anticalmodulin activity and with
      their antidiarrhoeal activities.

PMID- 1977621
TI  - Antithrombin Dublin (-3 Val----Glu): an N-terminal variant which has an aberrant
      signal peptidase cleavage site.
AB  - Antithrombin Dublin is an electrophoretically fast variant of antithrombin which
      has normal heparin affinity. Direct sequencing of amplified exon 2 revealed a Val
      ---Glu substitution at position -3. N-terminal sequencing of antithrombin from
      two individuals, heterozygous for the Dublin mutation, showed the presence of a
      truncated antithrombin in which the N-terminal dipeptide is absent. We propose
      that the prepeptide mutation redirects signal peptidase cleavage to a site two
      amino acids downstream into the mature protein.

PMID- 1977623
TI  - [Solder secure bond].

PMID- 1977622
TI  - [The duration of hormone synthesis by cultures of human fetal endocrine cells].
AB  - It is stated as possible to cultivate and accumulate endocrine cells by regular
      passages in vitro over a long period of time. In this case endocrine cells of
      human fetus don't loose the ability to synthesize hormone. Such cultures can be
      used to study some general-biological problems out of influence of the
      neurohumoral organism factors.

PMID- 1977624
TI  - [10th congress of the Society for Dermatology of GDR with international
      participation. Dresden, October 31-November 2, 1990. Abstracts].

PMID- 1977625
TI  - Basic and clinical aspects of GnRH-agonists in reproduction.
AB  - Within recent years GnRH agonists have gained increasing importance in the
      treatment of reproductive failure. Their use as a pretreatment for in vitro
      fertilization increases the pregnancy rate at least under certain conditions. In
      cases of endometriosis and uterus myomatosus, GnRH agonists achieve high
      remission rates and may avoid or at least postpone the need for surgical
      intervention. The physiological basis and current clinical strategies are
      discussed.

PMID- 1977626
TI  - Twin gestations and prophylactic hospitalization.
AB  - The study evaluates the benefit of elective hospitalization in preventing
      premature deliveries of twin gestations. Three groups of women with twin
      gestations, having no other complications of pregnancy which could cause
      premature delivery, were evaluated. The study group was comprised of 43 women who
      were electively hospitalized between 30-32 and 36 weeks of gestation. Control
      group 1 was comprised of 55 women who were not hospitalized but were instructed
      to rest at home. Control group 2 was comprised of 53 women who were not
      hospitalized and were not instructed to rest at home. Our results showed that
      elective hospitalization did not significantly affect the gestational duration or
      the prematurity rate. However the mean birthweight difference between the study
      group and the two control groups were 143 +/- 83 g and 205 +/- 84 g,
      respectively. This result was more significant in multiparous women. The slight
      increase in birthweight of the hospitalized women compared to the controls, does
      not seem to justify the cost of hospitalization.

PMID- 1977627
TI  - Maternal sickle cell trait is not a cause of low birthweight in Nigerian
      neonates.
AB  - As a result of reports of reduced birthweight in neonates of mothers with
      hemoglobin AS (Hb-AS) in other populations, we compared birthweights in 57 Hb-AS
      primigravidas in Nigeria with 60 controls who were sickle negative. There was no
      statistically significant difference in mean birthweight or placental weight
      between the groups. This finding may be due to development of resistance against
      malaria infection by Hb-AS women in this population.

PMID- 1977628
TI  - Neonatal neurological morbidity in relation to obstetrical and social conditions
      in Grenada (Caribbean).
AB  - Neonatal morbidity, in particular neurological morbidity is a more relevant
      measure of the effectiveness of obstetrical care than perinatal mortality.
      Neurological morbidity was assessed in a birth cohort in Grenada, and appeared to
      be lower than in a reference group examined in Groningen, the Netherlands, in
      1975-1978. Perinatal mortality, however, was higher. The results support the
      thesis that some children may have died who, if they would have survived, would
      have been neurologically abnormal. It is concluded that whereas a decrease in
      perinatal deaths is an essential goal in Grenada, a concomitant increase in
      morbidity should be carefully avoided.

PMID- 1977629
TI  - Surgical control of obstetric hemorrhage: hypogastric artery ligation or
      hysterectomy?
AB  - Sixty-four patients with severe postpartum hemorrhage (PPH) required surgical
      intervention during the years 1983 to 1987. Bilateral hypogastric artery ligation
      (HAL) was the initial surgical approach in 45% (29/64) and hysterectomy in 55%
      (35/64). HAL successfully controlled hemorrhage in 65% (19/29), and failed in 35%
      (10/29) where hysterectomy was required as a life saving procedure. Failure of
      HAL was more evident in atonic PPH than in other situations. Complications were
      more following hysterectomy; six (6/45) patients required re-exploration for
      intraperitoneal hemorrhage and two (2/45) patients died following hysterectomy.
      HAL was found to be a relatively easy, safe and successful procedure to be
      attempted as an initial surgical approach for all severe PPH, specially where
      uterine conservation was desired.

PMID- 1977630
TI  - Prevention of hepatitis B infection in infants born to hepatitis B carrier
      mothers: low dosage vaccination.
AB  - Two groups of newborn infants born to HBeAg positive carrier mothers were given
      HBIG (200 IU) immediately after birth. Subsequently, at age 2 days and at 1, 2
      and 12 months, the first group received 5 microgram and the second group 2
      microgram of HBV vaccines. There was no significant difference in the anti-HBs
      seroconversion rate (SR), and the protective efficacy rate (PER) at the age of 13
      months in either group. The SR and PER of group 1 were 91.7% and 90.18%, and
      group II were 92.9% and 91.01%, respectively. Although the significant
      differences were observed in the geometric mean titers of anti-HBs in group I
      (526.3 mIU/ml) and group II (371.4 mIU/ml), both were above the protective level.
      The immune responses to the reduced dosage of HBV vaccines are satisfactory in
      preventing HBV in the newborn infants of HBeAg positive carrier mothers.

PMID- 1977631
TI  - Hydatidiform mole: clinicopathologic associations with the development of
      postevacuation trophoblastic disease.
AB  - Clinical information and histopathologic material for 165 patients with
      hydatidiform mole referred to the John I. Brewer Trophoblastic Disease Center of
      Northwestern University Medical School during one year were reviewed in order to
      identify characteristics more likely to be associated with the development of
      gestational trophoblastic tumors. Twenty-nine patients (18%) required
      chemotherapy for invasive mole or choriocarcinoma. Patients with uterine
      enlargement beyond that expected for dates and patients with ovarian theca-lutein
      cysts were much more likely to require treatment after molar evacuation (47% vs.
      18% and 40% vs. 16%, respectively). There was no correlation between the initial
      human chorionic gonadotropin level, gestational age, uterine size per se,
      maternal age or gravidity and the subsequent clinical course. Histologically, the
      following factors were associated with an increased incidence of postmolar
      gestational trophoblastic tumor: (1) progressive nuclear atypia (26.7% if atypia
      present vs. 40% if absent); (2) necrosis and hemorrhage (39.1% if extensive vs.
      12.8% if limited); (3) decreased trophoblast maturation (48% if less than 20%
      mature vs. 8.7% if greater than or equal to 20% mature); (4) trophoblast
      proliferation (50% if marked vs. 13.9% if limited); (5) increased ratio of
      cytotrophoblast to syncytium (33.3% if greater than 1 vs. 6.4% if less than 1);
      and (6) absence of Nitabuch's layer (21.4% if absent vs. 11.6% if present).
      Hydatidiform moles which demonstrate clinical or histopathologic evidence of
      excessively abnormal proliferative activity, as indicated by these features, are
      more likely to develop invasive mole or choriocarcinoma and should be considered
      for prophylactic chemotherapy.

PMID- 1977633
TI  - Gravid uterus in an anterior abdominal wall hernia of a Nigerian woman.
AB  - A case of a gravid uterus in an incisional hernia in the anterior abdominal wall
      of a 27-year-old Nigerian woman is presented. The patient developed an ulceration
      of the anterior abdominal wall necessitating prolonged hospitalization. She was
      delivered by emergency lower segment cesarean section at 35 weeks gestational age
      because of premature labor. The patient unfortunately died from primary
      postpartum hemorrhage.

PMID- 1977632
TI  - Timing of ovulation in spontaneous and induced cycles.
AB  - We studied 30 spontaneous cycles, 30 cycles induced with clomiphene citrate, and
      30 cycles induced with human menopausal gonadotropin-human chorionic gonadotropin
      to evaluate the pattern of the following parameters and their predictive value in
      timing ovulation: basal body temperature; cervical mucus; mean follicular
      diameter; serum LH and 17-beta-estradiol; and urinary LH. Compared with the
      spontaneous cycles, in the cycles induced with clomiphene citrate the cervical
      score was significantly lower on the 4 days preceding ovulation, serum LH was
      higher in the early follicular phase, and serum 17-beta-estradiol was
      significantly higher in the pharmacologically treated cycles. The highest
      predictive values in all groups of cycles were obtained by considering the
      following combinations of parameters: serum 17-beta-estradiol and LH
      concentrations; mean follicular diameter as shown by ultrasonography and urinary
      LH as determined by a rapid method.

PMID- 1977634
TI  - Post-molar trophoblastic disease following coexisting molar pregnancy and living
      fetus subsequent to clomiphene citrate therapy.
AB  - A case of the combination of a complete hydatidiform mole and a coexisting,
      living fetus arising from a twin pregnancy, subsequent to clomiphene citrate
      therapy for ovulation induction, is presented. The diagnostic problems of this
      combination as well as the incidence of molar pregnancy following the use of
      ovulation inducers are discussed.

PMID- 1977635
TI  - Cesarean section--indications and risks in rural Zaire.
AB  - In a retrospective study in rural Zaire, 10.2% of all deliveries were conducted
      by cesarean section. Common indications were contracted pelvis and uterine
      dysfunction (37%) and previous cesarean delivery (32%). Compared with normal
      delivery, mortality was higher after cesarean section. Cesarean section should
      only be performed by well-trained personnel and when vaginal delivery is deemed
      inappropriate.

PMID- 1977636
TI  - Obstetric outcome among Vietnamese refugees in Hong Kong: an age-matched case
      controlled study.
AB  - The obstetric performance of 308 Vietnamese refugees is compared with that of 308
      age-matched Hong Kong Chinese patients. Vietnamese women were of higher parity
      and had an increased incidence of late booking and unreliable dates. Significant
      differences were found in the incidence of previous termination of pregnancy,
      iron-deficiency anemia, parasitic infestation, tuberculosis (TB) and syphilis.
      There was no significant difference in the mean birthweight between the two
      groups. However, there were twice as many low birthweight (less than 2500 g)
      infants amongst the Vietnamese whereas the Chinese patients had a higher
      incidence of macrosomic (greater than 4 kg) infants. There were no perinatal
      deaths and no significant perinatal morbidity.

PMID- 1977637
TI  - Eclampsia and fetal sex.
AB  - The study of the possible importance of the sex of the fetus on the frequency and
      clinical characteristics of 777 singleton pregnancies complicated by antepartum
      eclampsia showed that; (1) the male to female ratio for the total group was
      1.23/1, (2) this figure was 1.27/1 in first pregnancies and 1.32/1 in patients
      less than 20 years old, (3) the ratio increased to 1.44/1 in women more than 30
      years of age, and (4) in contrast, 169 postpartum eclampsia cases had a male to
      female ratio of 1.07/1. There were no statistically significant differences in
      the obstetric profiles, the main eclamptic symptoms or the fetomaternal mortality
      figures attributable to the sex of the fetus. However, since eclampsia is more
      severe in older women, the clinician may see more complications and maternal
      deaths associated with male fetuses because of their significantly higher ratio.
      In addition, these findings suggest that the presence of a male fetus with a
      hormonal and genetic code more different from the mother than with female
      offspring may be an accessory to the fundamental causes of this disease.

PMID- 1977638
TI  - Intrauterine growth retardation: characteristics, risk factors and gestational
      age.
AB  - Maternal, obstetrical, and neonatal factors were studied in 1604 pregnancies
      complicated by intrauterine growth retardation and 1604 non-IUGR controls. These
      were examined in the overall IUGR group and at various gestational ages. Eighty
      six percent of perinatal deaths were found in the IUGR group with 57.4% occurring
      prior to labor. Maternal smoking, low weight gain, low prepregnancy weight, and
      hypertension were found more frequently in the IUGR population. In addition,
      maternal hypertension was found to be significant in the IUGR infants delivered
      prematurely.

PMID- 1977639
TI  - Anamnestic pregnancy risk assessment.
AB  - Based on data obtained from the 1984-1985 Guadeloupean Perinatal Audit, a
      pregnancy risk scoring system was developed using maternal demographic,
      socioeconomic, obstetric history and risk characteristics recorded at the first
      prenatal visit. Various combinations of risk factors were identified for four
      distinct pregnancy outcomes (perinatal mortality, low birth weight, preterm
      delivery and intra-uterine growth retardation). The findings emphasize the
      importance of developing risk assessments for discrete pregnancy outcomes within
      specific populations.

PMID- 1977640
TI  - A multifactorial study of birth place options: improving health care delivery in
      Saudi Arabia.
AB  - Although consumer demands may dictate a review of the highly mechanized and
      sophisticated technology of obstetric care provided in some parts of the western
      world, problems in Saudi Arabia revolve around under-utilization of health care
      facilities for maternity care and the consequences of this circumstance. A
      multifactorial analysis was performed to study the association of certain social
      correlates with options for birth settings in a rural region of the Kingdom. Age
      and educational level of the mother were found to be highly significant (P less
      than 0.005) variables influencing the choice for place of delivery, whereas
      economic status (P greater than 0.1) and housing conditions (NS) tailed to make
      an equally impressive contribution. Within the constraints of available health
      care manpower at the local level, suggestions are made for the best strategy to
      successfully educate mothers for safer options in birth.

PMID- 1977641
TI  - Obstetric anesthetic outpatient clinics: an international survey.
AB  - An international investigation was undertaken into practices of pre-anesthetic
      evaluation provided for obstetrical patients in outpatient clinics. A
      questionnaire was completed by 21/36 (58%) obstetric units. Only 5 (23%) had an
      outpatient clinic for preanesthetic evaluation of the obstetric patient, but in
      10 (37%) anesthetists take part in the prenatal examinations and give advice in
      cases of complicated pregnancy.

PMID- 1977642
TI  - Ectopic pregnancy in a defined Nigerian population.
AB  - All cases of ectopic pregnancy in the Ile-Ife teaching hospital between 1977 and
      1987 were reviewed. The incidence per 1000 births was 4.76, and this condition
      accounted for 2.75% of all gynecological admissions. The associated mortality was
      low (0.5%). An increasing incidence was observed during the study period, as was
      an increasing proportion of nulliparous patients. Tubal damage from pelvic
      infections might account for the trends.

PMID- 1977643
TI  - Ovarian fibroma--clinical and histopathological characteristics.
AB  - Twenty-three cases of ovarian fibroma, comprising 3% of all benign tumors seen
      over a 20-year period, were analyzed. It was unilateral in all cases affecting
      more commonly the left ovary (70%). Whilst a majority of cases (77%) were
      encountered in the reproductive age group, the tumor was rare before the second
      decade. Only in 13% of cases was ascitis clinically detectable. This was not
      influenced by the size and weight (average of 9.3 x 10.8 x 11.1 cm and 959 g,
      respectively) of the tumors; a smooth-surfaced tumor was, however, associated
      with a greater amount of peritoneal fluid. Varying degrees of calcification in
      some tumors are detectable on ultrasonography and occasionally on abdominal
      radiography. The classical Meig's Syndrome was seldom encountered. The
      histopathological features, diagnostic problems and management are discussed.

PMID- 1977644
TI  - Carcinoma of the cervix in the African setting.
AB  - Carcinoma of the cervix is the commonest female malignancy in sub-Saharan Africa
      today. A brief description of its prevalence and distribution is given. Kenyan
      data is then used to illustrate the predominance of advanced disease in mostly
      premenopausal women (70%) of high parity. Follow up is characteristically poor
      and treatment results, although difficult to calculate with accuracy, are also
      poor. These are compared to FIGO statistics. Against this background aspects
      peculiar to the tumor, patient and treatment facilities in Africa are cited and
      discussed with reference to current relevant literature.

PMID- 1977645
TI  - Effects of oral contraceptive pills on serum lipoproteins and triglycerides.
AB  - Possible effects of a combined oral contraceptive (femenal) on blood
      triglycerides and high-density-lipoprotein-cholesterol (HDL-Chol) were studied in
      25 women who had opted for hormonal contraception. Total serum triglycerides of
      64.60 +/- 12.39 mg/dl (mean +/- SD) obtained prior to the commencement of
      hormonal contraception, did not reveal any statistical difference from the value
      of 65.49 +/- 7.96 mg/dl obtained after 9 months contraception. Similarly,
      precontraception HDL-Chol value of 58.05 +/- 6.58 mg/dl was also not
      statistically different from the treatment value of 58.82 +/- 5.42 mg/dl.
      Regression analysis of the values between control (precontraception) and
      treatment (9 months contraception) showed high correlation coefficients: (1)
      serum triglycerides, R2 = 0.5201; P less than 0.001; (2) serum HDL-Chol, R2 =
      0.6590; P less than 0.001. Both the mean body weight and blood pressure of the
      study subjects remained unchanged after 9 months continuous use of femenal for
      contraception.

PMID- 1977646
TI  - Comparative study of Filshie clip and Pomeroy method for postpartum
      sterilization.
AB  - A prospective randomized comparison of the peri-operative complications and long
      term sequelae between the Filshie clip and Pomeroy methods was undertaken in 200
      postpartum women at Tri-Service General Hospital, Taipei, Taiwan. The peri
      operative complications in either group were mild and infrequent. One pregnancy
      in the Pomeroy group was reported after follow-up for 24 months. No significant
      difference between the two groups was found in respect to long-term sequelae.

PMID- 1977647
TI  - Maternal ECG recorded by internal monitoring closely mimicking fetal heart rate
      in a recent fetal death.
AB  - A case of intrapartum fetal death in which the maternal heart rate was recorded
      by internal fetal monitoring is presented. The electrical activity of the
      maternal heart was transmitted via the fetal body and the recording mimicked a
      "normal" fetal heart rate (FHR). The patient was referred because of sudden
      abdominal pain and bleeding; Doppler fetal heart tones were not heard. Because
      internal monitoring was synchronous with the maternal pulse, ultrasonography was
      performed and established the diagnosis of fetal demise. Awareness and usage of
      simple modalities are mandatory for proper diagnosis in such cases.

PMID- 1977648
TI  - Rupture of the gravid uterus following a road traffic accident.
AB  - A case of rupture of the uterus at 34 weeks of pregnancy due to a road traffic
      accident is presented. Emergency laparotomy and total abdominal hysterectomy were
      done with good maternal outcome. This is a rare cause of rupture of the uterus in
      this population.

PMID- 1977649
TI  - Recurrent pulmonary embolism in pregnancy managed with the Greenfield vena caval
      filter.
AB  - Recurrent embolisation from venous thrombosis despite anticoagulation, in
      pregnancy, constitutes a major diagnostic and management problem. We present just
      such a patient who was managed with a Greenfield vena caval filter, which enabled
      her pregnancy to continue, resulting in a vaginal delivery of a healthy female
      infant at 38 weeks gestation.

PMID- 1977651
TI  - [The time dependence of work-related psychophysiological reorganization in
      information systems operators].

PMID- 1977650
TI  - Multiple alterations in insulin responses to glucose in islets from 48-h glucose
      infused nondiabetic rats.
AB  - To examine the biochemical mechanisms by which hyperglycemia produces insulin
      secretory abnormalities, we studied isolated islets from control rats and rats
      infused for 48 h with a 50% glucose solution. To preserve the effects of in vivo
      hyperglycemia during in vitro handling for islet isolation, our standard
      isolation procedure utilized buffers containing 16.8 mM glucose. Islets from
      infused rats released similar amounts of insulin in low or high glucose during
      first incubations at 37 degrees C (92.4 +/- 7.0 ng.10 islets-1.45 min-1 at 2.8
      mM, 84.4 +/- 4.1 ng.10 islets-1.45 min-1 at 16.8 mM) in contrast with control
      (uninfused) islets (18.6 +/- 2.8 ng.10 islets-1.45 min-1 at 2.8 mM and 109.8 +/-
      8.0 ng.10 islets-1.45 min-1 at 16.8 mM glucose) (P less than 0.01). Secretion by
      islets of glucose-infused rats was lower during 60-min second incubations at 28
      mM glucose than in first incubations of the same islets in low glucose (P less
      than 0.01). This phenomenon is comparable to the paradoxical hypersecretion
      observed during the first 10-15 min of exposure of glucose-infused pancreas to
      low-glucose perfusions. Paradoxical secretion in low glucose waned rapidly, so
      that during second incubations at 37 degrees C, little immunoreactive insulin
      release occurred at 2.8 mM glucose, despite the persistence of two additional
      lesions. The glucose-insulin dose-response curves in second incubations showed a
      leftward shift for glucose-infused islets, with two- to threefold higher
      secretion at 5.6-8.4 mM glucose than control islets. This is termed sensitization
      to glucose.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1977652
TI  - Proceedings of the International Symposium on Molecular Biology of Hepatitis B
      Virus and Non-A Non-B Hepatitis Virus. June 1, 1989, Kanazawa, Japan.

PMID- 1977653
TI  - Inhibitory effect of pancreastatin on pancreatic exocrine secretions.
      Pancreastatin inhibits central vagal nerve stimulation.
AB  - The effects of the C-terminal fragment of rat pancreastatin on exocrine
      pancreatic secretions induced by several neural stimulations [IV injection of 75
      or 15 mg/kg of 2-deoxy-D-glucose (central vagal nerve stimulation), injection of
      2 mg of cisapride (proposed to elicit acetylcholine release from cholinergic
      nerve ending), and infusion of 1 or 3 mg.kg-1.h-1 of bethanechol (direct
      stimulation of acinar cells)] were examined in conscious rats. Rats with external
      bile and pancreatic fistulae were used. All the stimulations caused significant
      increases in pancreatic exocrine secretions. Pancreastatin at 100 pmol.kg-1.h-1
      inhibited pancreatic secretions stimulated by IV injection of 2-deoxy-D-glucose
      but not those induced by the infusion of bethanechol or the injection of
      cisapride. Because these findings showed that pancreastatin inhibited pancreatic
      secretions induced by central vagal nerve stimulation, the effect of
      pancreastatin on cholecystokinin-stimulated pancreatic secretions in vagotomized
      rats was examined. Pancreastatin at 100 pmol.kg-1.h-1 did not inhibit pancreatic
      secretions stimulated by cholecystokinin octapeptide at 100 pmol.kg-1.h-1 in
      conscious rats after bilateral truncal vagotomy. These results suggest that
      pancreastatin inhibits pancreatic exocrine secretions by inhibiting vagal
      efferent nerve activity.

PMID- 1977654
TI  - Genetic variation at the apolipoprotein gene loci contribute to response of
      plasma lipids to dietary change.
AB  - Dietary intervention studies (from a low polyunsaturated/saturated fatty acid
      ratio P/S diet to a high P/S diet), carried out on a group of healthy individuals
      from North Karelia, Eastern Finland between 1981-1984, provided evidence that
      there may be a genetic component contributing to variation in response to dietary
      change. We have resampled blood from 107 individuals involved in the original
      studies and used Restriction Fragment Length Polymorphisms (RFLPs) to study the
      genetic contribution of variation at a number of candidate gene loci to the
      response to dietary change. The genes investigated in this study were the
      apolipoprotein (apo) genes: apo B, apo AII, apo E (protein polymorphism), apo AI
      CIII-AIV gene cluster, and the LDL-receptor gene. On the basal diet the major
      effect of genotype on lipid traits was due to variation at the apo E gene locus;
      this protein polymorphism explained 14.6% of the phenotypic variance in LDL
      cholesterol levels and 12.7% of the phenotypic variance in total cholesterol
      levels. When switched to low fat high P/S diet, these effects of variation at the
      apo E gene locus on the phenotypic variation of LDL and total cholesterol levels
      disappeared. The major effect on the response to dietary change, delta, was seen
      on the difference in apo AI levels mediated by variation at the apo B gene locus
      (MspI RFLP) explaining 6.3% of the phenotypic variance in apo AI change. For the
      RFLPs of the apo AI-CII-AIV gene cluster, small but not significant differences
      on delta were found. Our results indicate that within the limits of the candidate
      genes studied, the major effects in response to dietary change was on apo AI
      levels mediated through variation at the apo B gene locus.

PMID- 1977655
TI  - Developmental genetic analysis of Contrabithorax mutations in Drosophila
      melanogaster.
AB  - A developmental analysis of the Contrabithorax (Cbx) alleles offers the
      opportunity to examine the role of the Ultrabithorax (Ubx) gene in controlling
      haltere, as alternative to wing, morphogenesis in Drosophila. Several Cbx alleles
      are known with different spatial specificity in their wing toward haltere
      homeotic transformation. The molecular data on these mutations, however, does not
      readily explain differences among mutant phenotypes. In this work, we have
      analyzed the "apogenetic" mosaic spots of transformation in their adult
      phenotype, in mitotic recombination clones and in the spatial distribution of Ubx
      proteins in imaginal discs. The results suggest that the phenotypes emerge from
      early clonality in some Cbx alleles, and from cell-cell interactions leading to
      recruitment of cells to Ubx gene expression in others. We have found, in
      addition, mutual interactions between haltere and wing territories in pattern and
      dorsoventral symmetries, suggesting short distance influences, "accommodation,"
      during cell proliferation of the anlage. These findings are considered in an
      attempt to explain allele specificity in molecular and developmental terms.

PMID- 1977656
TI  - Genetic analysis of the enhancer of zeste locus and its role in gene regulation
      in Drosophila melanogaster.
AB  - The Enhancer of zeste [E(z)] locus of Drosophila melanogaster is implicated in
      multiple examples of gene regulation during development. First identified as
      dominant gain-of-function modifiers of the zeste1-white (z-w) interaction, mutant
      E(z) alleles also produce homeotic transformations. Reduction of E(z)+ activity
      leads to both suppression of the z-w interaction and ectopic expression of
      segment identity genes of the Antennapedia and bithorax gene complexes. This
      latter effect defines E(z) as a member of the Polycomb-group of genes. Analysis
      of E(z)S2, a temperature-sensitive E(z) allele, reveals that both maternally and
      zygotically produced E(z)+ activity is required to correctly regulate the segment
      identity genes during embryonic and imaginal development. As has been shown for
      other Polycomb-group genes, E(z)+ is required not to initiate the pattern of
      these genes, but rather to maintain their repressed state. We propose that the
      E(z) loss-of-function eye color and homeotic phenotypes may both be due to gene
      derepression, and that the E(z)+ product may be a general repressing factor
      required for both examples of negative gene regulation.

PMID- 1977657
TI  - DNA sequence variation within maize and melon: observations from polymerase chain
      reaction amplification and direct sequencing.
AB  - While compiling genetic linkage maps in several plant species based upon
      restriction fragment length polymorphisms (RFLPs), it was noted that the
      incidence of polymorphism differs among species. The basis of this disparity was
      investigated in this study by examining the nucleotide sequence at homologous
      loci among distinct cultivars within two species which exhibit considerably
      different levels of RFLPs. Using the polymerase chain reaction, homologous
      regions from different cultivars were first amplified and the nucleotide sequence
      of the products were determined. Four genomic regions of seven maize cultivars
      and three genomic regions of eight melon cultivars were examined to compare the
      respective levels of sequence variation between the two species. Levels of
      variation for both base substitutions and insertions/deletions varied widely
      among the maize sequences and between maize and melon for base substitutions.
      Estimates of theta (a measure of polymorphism) ranged from 0 to 0.002 in melon
      and from 0.006 to 0.040 for base substitutions and from 0.002 to 0.023 for
      insertions/deletions in maize. Critical value tests and chi-squared tests
      suggested that in maize the underlying processes generating and maintaining
      neutral mutations differ among the regions. The results not only suggest that
      several mechanisms are necessary to explain the variation seen in these two
      species, but also point to some basic dissimilarities in the organization and
      maintenance of the genomes of different plant species.

PMID- 1977659
TI  - A homeo domain protein reveals the metameric nature of the developing chick
      hindbrain.
AB  - The segmented embryonic hindbrain of vertebrates develops by sequential
      constriction of the neural tube into eight metameric units known as rhombomeres.
      The cellular and molecular basis of this segmentation process is largely unknown.
      Using an antibody, we analyzed the expression pattern of the chick homeo domain
      containing protein Ghox-lab in the developing chick hindbrain. At the neural
      plate stage, prior to the appearance of rhombomeres, Ghox-lab is expressed within
      a single domain that extends anteriorly up to the site where rhombomere 4 will
      later form. After rhombomere 4 has appeared and as hindbrain segmentation
      progresses, the level of Ghox-lab protein increases significantly within the
      fourth rhombomere. This intensification, accompanied by the elimination of Ghox
      lab protein in rhombomeres 5 and 6, eventually results in the formation of a
      distinct island of expression in rhombomere 4. All cells in the newly formed
      rhombomere 4 express Ghox-lab, except for the cells of the floor plate. In
      addition, neural crest cells migrating from the fourth rhombomere are also Ghox
      lab-positive. These data raise the possibility that Ghox-lab protein might be one
      of the factors involved in the specification of the metameric pattern of the
      vertebrate hindbrain.

PMID- 1977658
TI  - Behavior of the [mi-3] mutation and conversion of polymorphic mtDNA markers in
      heterokaryons of Neurospora crassa.
AB  - We have examined the behavior of the [mi-3] mitochondrial mutation and two
      physical mtDNA markers in heterokaryotic cultures of Neurospora crassa. Previous
      workers showed that a 1.2-kilobase insertion in the larger polymorphic form of
      EcoRI-5 restriction fragment is a site of high frequency and rapid unidirectional
      gene conversion. We have confirmed this observation and determined by DNA
      sequence analysis that the insertion in the EcoRI-5 fragment corresponds
      precisely to an optional intron that contains a long open reading frame in the
      ND1 gene. Thus, the conversion of the short, intron-lacking, form of EcoRI-5 to
      the longer, intron-containing, form may be analogous to the unidirectional gene
      conversion events catalyzed by intron-encoded proteins in other organisms. The
      resolution of two polymorphic forms of the mtDNA EcoRI-9 restriction fragment in
      our heterokaryons differs from that observed previously and suggests that this
      locus is not a site of gene conversion in our heterokaryon pair. The size
      polymorphism of the EcoRI-9 fragments is due to a tandemly reiterated 78-base
      pair sequence which occurs two times in the short form and three times in the
      long form. One copy of the repeat unit and 66 base pairs following it have been
      duplicated from the ND2 gene which is located about 30 kilobases distant on the
      mtDNA. In contrast to the [poky] mitochondrial mutant, which was completely
      dominant over wild-type mitochondria in heterokaryons, the [mi-3] mutant was
      recovered in only seven of twenty heterokaryons after ten cycles of conidiation
      and subculturing. The resolution of the [mi-3] or wild-type phenotype in
      heterokaryons may depend solely on random factors such as allele input frequency,
      drift, and segregation rather than specific dominant or suppressive effects.

PMID- 1977660
TI  - A cloned human cDNA determines expression of a mouse stage-specific embryonic
      antigen and the Lewis blood group alpha(1,3/1,4)fucosyltransferase.
AB  - The stage-specific embryonic antigen SSEA-1 is a cell-surface oligosaccharide
      molecule expressed with temporal precision during the murine preimplantation
      period and implicated in adhesive events involving the process of compaction. We
      used a mammalian transient expression system to isolate a cloned human cDNA that
      determines expression of the SSEA-1 molecule. The cDNA sequence predicts a type
      II transmembrane protein with a domain structure similar to mammalian
      glycosyltransferases, but without primary sequence similarity to these enzymes.
      The carboxy-terminal domain of this protein was shown to be catalytically active
      as a fucosyltransferase when expressed in COS-1 cells as a portion of a secreted
      protein A fusion peptide. The enzyme is an exceptional glycosyltransferase in
      that it can use both type I and type II oligosaccharides as acceptor substrates
      to generate subterminal Fuc alpha(1,4)- and Fuc alpha(1,3)-linkages,
      respectively, in a manner analogous to the human Lewis blood group
      fucosyltransferase. Southern blot analysis shows that the cDNA corresponds to
      sequences syntenic to the Lewis locus on chromosome 19. These results indicate
      that this cDNA is the product of the human Lewis blood group locus, provide
      genetic confirmation of the hypothesis that this enzyme can catalyze two distinct
      transglycosylation reactions, and outline an approach to the isolation of other
      sequences that determine expression of developmentally regulated oligosaccharide
      antigens.

PMID- 1977661
TI  - Patterns of expression of cut, a protein required for external sensory organ
      development in wild-type and cut mutant Drosophila embryos.
AB  - The loss of cut activity in Drosophila results in the transformation of the
      neurons and support cells of external sensory (es) organs into those of
      chordotonal (ch) organs. The cut locus encodes a homeo domain-containing protein,
      which is expressed in the cells of es, but not in ch, organs. We show by Western
      analyses the presence of two embryonic protein species whose approximate relative
      molecular masses of 280 and 320 kD are compatible with that predicted from the
      primary sequence. We also describe the development of the Cut protein expression
      pattern and show that Cut is expressed in sensory precursor cells that divide to
      give rise to es organs. Finally, we analyze the changes in the Cut expression
      pattern of several mutant alleles of the complex cut locus and show that the
      mutations affecting es organ development are associated with either altered
      protein distribution in the PNS or incorrect subcellular Cut protein
      localization.

PMID- 1977662
TI  - In vivo monitoring of a cAMP-stimulated DNA-binding activity.
AB  - The transcriptional activity of the tyrosine aminotransferase (TAT) gene is
      influenced by two major signal transduction pathways, by glucocorticoids and by
      glucagon acting via cAMP. We analyzed the effect of cAMP on protein-DNA
      interactions in vivo and on the transcription rate of the TAT gene. We
      demonstrate that a cAMP-responsive element (CRE) is located in a tissue-specific
      DNase I-hypersensitive region, 3.6 kb upstream of the start site of
      transcription. By using the genomic footprinting technique, we show that this
      sequence is occupied by protein in uninduced cells and that the in vivo footprint
      is transiently increased upon cAMP induction. Protein binding at the TAT-CRE
      correlates with the rate of transcription of the TAT gene. Cycloheximide
      treatment reveals that the genomic footprint is subject to rapid turnover;
      however, subsequent cAMP induction in the continued presence of cycloheximide
      restores the footprint partially. We conclude that as a part of the signal
      transduction pathway, a cAMP-dependent, post-translational modification increases
      the DNA-binding activity of a protein to the TAT-CRE and thereby stimulates the
      transcription rate of the TAT gene.

PMID- 1977663
TI  - Nucleotide sequence of the histone H3-encoding gene from the scleractinian coral
      Acropora formosa (Cnidaria: Scleractinia).
AB  - The histone H3-encoding gene from the staghorn coral Acropora formosa has the 3'
      hairpin structure which functions as termination/processing signal in
      nonpolyadenylated histone mRNAs. The predicted amino acid sequence is highly
      homologous with the major H3 histones of higher metazoans, and has least homology
      with the corresponding protist and fungal proteins. These data are inconsistent
      with the phylogenetic position which has been assigned to the Cnidaria by partial
      18S rRNA sequence comparison.

PMID- 1977664
TI  - Treatment of urinary incontinence: the place of drugs.
AB  - A good pharmacological treatment of urinary incontinence must be based on an
      appropriate understanding of the underlying physiological disturbance and on a
      basic knowledge of drugs, their mode of action on the urinary tract and their
      side effects. A general drug treatment policy must be established. This involves
      indications for treatment with the best drug, adjustment of the dosage, follow-up
      of the patient as well as the combination of drug treatment with
      nonpharmacological interventions like behavioral treatment procedures and pelvic
      floor training.

PMID- 1977665
TI  - Melatonin secretion and the pathophysiology of Meige's disease (idiopathic
      orofacial dystonia): a hypothesis.
AB  - Meige's disease is a form of focal dystonia characterized by symmetric dystonic
      spasms of facial muscles, sometimes associated with dystonic movements of other
      midline muscle groups. The etiology and pathophysiology of the disease have not
      been established. There is evidence that Meige's disease may result from striatal
      dopaminergic preponderance coupled with cholinergic overactivity. Several authors
      have noted a high prevalence of depression in patients with Meige's disease,
      suggesting a common neurochemical abnormality. Depression, in turn, is associated
      with decreased pineal melatonin secretion. We propose, based on studies
      demonstrating that melatonin regulates dopaminergic, cholinergic and GABA-ergic
      functions, that alterations in melatonin functions may enhance the development of
      the disease. This hypothesis may open new avenues toward understanding the
      pathophysiology of the disease and developing newer therapeutic strategies.

PMID- 1977666
TI  - Clinical usefulness of serum sialyl SSEA-1 antigen levels in patients with
      epithelial ovarian cancer. Comparative effectiveness of sialyl SSEA-1 and CA 125.
AB  - The serum levels of sialyl SSEA-1 antigen, a type 2 chain carbohydrate antigen
      detected using the monoclonal antibody FH-6, were elevated in 47.2% of patients
      with epithelial ovarian cancer, with the percent positivity increasing with the
      clinical stage. Of the histological type, it is interesting to note the
      relatively high sensitivity in patients with mucinous adenocarcinoma and clear
      cell carcinoma in contrast with the CA 125 antigen levels. Although the
      percentage of patients with ovarian cancer who had elevated sialyl SSEA-1 antigen
      levels is lower than that observed with elevated CA 125 antigen levels, the false
      positive rate is significantly low in the sialyl SSEA-1 test. Serial sialyl SSEA
      1 antigen levels obtained during follow-up were strong predictors of clinical
      outcome. The combined determination possible with sialyl SSEA-1 and CA 125 did
      not markedly increase the detection rate because of the overlap in the
      positivity. However, increased levels of both serum sialyl SSEA-1 antigen and CA
      125 antigen indicated the presence of malignancies in pregnant women associated
      with ovarian tumors.

PMID- 1977667
TI  - Blood cell growth factors: their biology and clinical applications.

PMID- 1977668
TI  - P-glycoprotein expression in multiple myeloma.
AB  - P-glycoprotein expression was investigated in ten drug resistant patients
      suffering from multiple myeloma. The immunoperoxidase method on bone marrow
      plasma cells and immunoblotting were performed by using the monoclonal antibody
      C219. Five patients resistant to protocols including vincristine, melphalan and
      doxorubicin were found to express P-glycoprotein. The immunoperoxidase method
      appeared to be sensitive and suitable for P-glycoprotein detection in bone marrow
      samples.

PMID- 1977669
TI  - Nicardipine as a chemosensitizing agent in two P-glycoprotein-positive leukemic
      patients.

PMID- 1977670
TI  - [Antihypertensive effects of betaxolol, a cardioselective beta-adrenoceptor
      antagonist, in stroke-prone spontaneously hypertensive rats (SHRSP)].
AB  - Effects of betaxolol, a cardioselective beta-adrenoceptor antagonist, on blood
      pressure and hypertensive complications in stroke-prone spontaneously
      hypertensive rats (SHRSP) were investigated. Betaxolol was provided in a dose of
      33 +/- 1.8 mg/kg/day, orally in drinking water, throughout the experimental
      period. The chronic treatment with betaxolol inhibited the development of
      hypertension in SHRSP and reduced values of blood urea nitrogen, creatinine,
      total cholesterol, free cholesterol, triglyceride, phospholipid and HDL
      cholesterol in serum. Treatment with betaxolol apparently inhibited the incidence
      of hypertensive lesions such as cardiac fibrosis, mesenteric vasculitis,
      proliferative and/or necrotic vasculitis and glomeruli showing collapse or
      vasculitis in the kidneys. To shorten the time before the onset of hypertension
      and the subsequent stroke, SHRSP were kept on a SP diet containing 0.39% Na
      instead of the F-2 diet. When the SHRSP were kept on the SP diet, all of the
      control SHRSP had cerebral apoplexy and severe hypertensive lesions in the heart
      and kidney. When betaxolol was chronically administered to SHRSP, cerebral
      apoplexy and hypertensive lesions in the heart and kidney were inhibited, but the
      effect on blood pressure was slight. Treatment with betaxolol reduced serum
      creatinine levels. Our observations show that betaxolol reduces blood pressure
      and potently inhibits hypertensive complications in SHRSP.

PMID- 1977671
TI  - [Ibuprofen in pain therapy. A reliable form of self-medication. Report of a
      conference. Bad Schonborn, Bruchsal, 12 May 1990].

PMID- 1977672
TI  - [Which half life for bad days?].

PMID- 1977673
TI  - [New directions in the therapy of ischemias and infarcts. ACE inhibitors improve
      survival rate. Report of a symposium. The Haag, 8 June 1990].

PMID- 1977674
TI  - [Josamycin strengthens the inborn resistance. Broad spectrum in respiratory tract
      infections without development of resistance. Report of a symposium. 22 May
      1990].

PMID- 1977675
TI  - [Stimulation of prostacycline synthesis to normalize hypertension slowly and with
      caution. Report of a symposium. 11-16 February 1990, Manila].

PMID- 1977676
TI  - [Noradrenaline-induced alterations in beta-adrenergic receptor-adenylate cyclase
      system of rat myocardium].
AB  - Although the agonist-induced down-regulation of beta-adrenergic receptors has
      been well documented, the investigations dealing with the agonist-induced changes
      in G-proteins are few and controversial. To elucidate the alterations in each
      components of the adenylate cyclase (AC) system, we infused subpressor doses of
      noradrenaline (NA) to WKY rats (20-week-old) for three different periods (3, -
      and 14 days) using osmotic minipumps. Beta-adrenergic receptor density measured
      by 125I-cyanopindolol binding assay, and forskolin-stimulated cyclase activity
      were both reduced markedly on the 3rd day of the treatment, and these effects
      persisted beyond the 14th day. Total amounts of the pertussis toxin substrates
      (inhibitory G-protein; Gi) increased significantly on the 7th day. On the other
      hand, those of the cholera toxin substrates (stimulatory G-protein: Gs) did not
      differ during the entire course of the treatment. We concluded that the down
      regulations of the beta-adrenergic receptor and the catalytic protein were the
      adaptative response to the increased extracellular stimuli, and that the
      alterations observed in Gi might also have an important role to inhibit the
      transduction of excessive stimulatory signal.

PMID- 1977677
TI  - Activity of enzymes involved in norepinephrine biosynthesis in the brown adipose
      tissue of the developing rat. Influence of hypothyroidism.
AB  - The activities of tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH)
      were measured in vitro in the brown adipose tissue (BAT) of control and
      hypothyroid developing rats. Neonatal hypothyroidism slows the development of TH
      activity, as manifest in lower BAT TH activity, relative to controls, up to 20
      days. This effect is more pronounced when the onset of hypothyroidism is induced
      prenatally. No clear effect of hypothyroidism on DBH activity was evident.

PMID- 1977678
TI  - Intravesical catheterization through the urethra induces stress hyperglycemia in
      conscious rats.

PMID- 1977679
TI  - Immunohistochemical demonstration of c-erbB-2 protein in mammary ductal carcinoma
      in situ.
AB  - The presence of the c-erbB-2 protein, demonstrated immunohistochemically with
      antibody 21N, has been studied in 72 cases of pure mammary ductal carcinoma in
      situ. Sixty-one percent of cases showed positive staining. The protein was always
      present in large-cell comedo type of ductal carcinoma in situ, and never in small
      cell cribriform/micropapillary type of ductal carcinoma in situ. When nuclear
      size was measured, staining was associated with tumors containing cells with
      large nuclei measuring up to 20 mu, and was never present in lesions containing
      cells with small nuclei measuring 10 mu or less. In tumors of mixed
      histopathologic type of ductal carcinoma in situ, variable staining was seen; the
      cells with small nuclei never stained, while the majority of cells with large
      nuclei reacted positively. The possible relevance of these findings to the
      biologic behavior of DCIS is discussed.

PMID- 1977680
TI  - TaqI HLA-B and -DRB RFLP analysis can predict disease in siblings of affected
      children with 21-hydroxylase deficiency.
AB  - The possibility of using TaqI restriction fragment length polymorphism (RFLP)
      analysis of the HLA-B locus and the HLA-DR-DQ subregions, flanking the 21
      hydroxylase genes, for predicting disease in siblings of children with 21
      hydroxylase deficiency was analyzed in 12 nuclear families with at least one
      affected child and a total of 18 at-risk off-spring. As part of the study allelic
      TaqI HLA-B RFLP patterns were determined in homozygous cell lines and families.
      The frequencies of individuals homozygous for TaqI allelic patterns of the
      different investigated HLA loci, each locus alone and in various combinations,
      were determined in 100 random controls. In all 12 families it was possible to
      make correct genetic diagnosis by the use of only one restriction enzyme, TaqI,
      and two locus-specific HLA cDNA probes, HLA-B and -DRB. In all families four
      haplotypes were obtained. Thus, affected siblings as well as carriers could be
      identified. Seven of the eight sibling pairs concordant for 21-hydroxylase
      deficiency had pairwise identical TaqI HLA-B-DRB-DQA-DQB haplotypes. The last
      disease-concordant sibling pair had inherited different haplotypes from their
      mother, who had nonclassical 21-hydroxylase deficiency. None of the ten healthy
      children shared both haplotypes with their affected sibling(s). Early prenatal
      suppression of the fetal adrenal cortex with fluorinated corticosteroids can
      prevent virilization of female fetuses with 21-hydroxylase deficiency. In most
      cases RFLP analysis of the 21-hydroxylase genes is not informative enough for
      prenatal diagnosis. Our results from the present retrospective family study
      indicate that TaqI HLA-B and -DRB RFP analysis will be a valuable tool for first
      trimester assessment of 21-hydroxylase deficiency. TagI HLA-B and -DRB RFLP
      analysis can be performed on DNA from chorionic villi biopsies obtained in the
      8th week of pregnancy. Supplemented with sex determination, early withdrawal of
      prophylactic steroid therapy will thus be feasible when the mother carries a male
      or an unaffected female fetus.

PMID- 1977681
TI  - The gene for 17 beta-hydroxysteroid dehydrogenase maps to human chromosome 17,
      bands q12-q21, and shows an RFLP with ScaI.
AB  - The gene encoding human 17 beta-hydroxysteroid dehydrogenase (17-HSD; EC
      1.1.1.62) is assigned to chromosome 17 by Southern blotting analyses of panels of
      human x rodent somatic cell hybrids and independently to 17q12-q21 using
      chromosomal in situ hybridization. A search for physical linkage between 17-HSD
      and the proto-oncogenes. THRA1 and ERBB2 (both reported to be located in this
      region of chromosome 17) was performed by pulsed-field gel electrophoresis (PFGE)
      using several rare-cutting restriction endonucleases. Because all three genes
      hybridized to DNA fragments of different lengths it seems unlikely that the gene
      for 17-HSD is located very close to THRA1 and ERBB2. Further evidence for this
      assumption was obtained from the absence of any coamplification of the 17-HSD
      gene in 9 breast tumors with amplification of the ERBB2 gene. Analyses of
      Southern blots of ScaI-digested DNAs from unrelated individuals from Northern
      Finland revealed a relatively infrequent diallelic restriction fragment length
      polymorphism, the allele frequencies of which were 0.04 (A1) and 0.96 (A2).

PMID- 1977682
TI  - The origin of sickle cell alleles in Israel.
AB  - Molecular genetic studies were undertaken to determine the source of chromosomes
      carrying the sickle cell allele in Israeli patients. Analysis of restriction
      fragment length polymorphism (RFLP) patterns (haplotypes) along the beta-globin
      gene cluster was performed on 31 sickle chromosomes obtained from 10 unrelated
      families living in Israel. One is a Caucasian Jewish family, recently found to be
      carrying the sickle allele, and the other 9 are Arab families of various
      communities. The Jewish family, previously noted not to carry African red blood
      cell markers, was discovered to have the most common African haplotype of the
      beta-globin gene cluster, Benin. Similarly, 8 of the Arab families were also
      found to carry the Benin haplotype, whereas the ninth has the CAR (Central
      African Republic or Bantu) haplotype. The results suggest that sickle alleles in
      Israel originated in Africa, probably in two different regions, and migrated
      north into Arab and Jewish populations.

PMID- 1977683
TI  - Amplification of the COL2A1 3' variable region used for segregation analysis in a
      family with the Stickler syndrome.
AB  - Amplification of a variable region 3' to the human type II collagen gene (COL2A1)
      has permitted segregation analysis in a three generation Stickler syndrome
      pedigree. This family had previously proved uninformative for the known
      restriction fragment length dimorphisms. Amplification of the variable region
      revealed five distinguishable alleles, of which three were segregating in this
      family. The lod score in favour of linkage was 2.86 at zero recombination.

PMID- 1977684
TI  - Linkage disequilibrium detected between dystrophia myotonica and APOC2 locus in
      the Finnish population.
AB  - Three polymorphic loci APOC2, CKMM and p134C were used to haplotype 15 Finnish
      dystrophia myotonica (DM) families representing about one third of all DM
      patients in this isolated population. Compound APOC2 and CKMM haplotypes reveal
      linkage disequilibrium: 90% of DM chromosomes co-occur with the haplotypes that
      occur in 31% of normal chromosomes only. The same disequilibrium is present when
      only polymorphisms occurring at the APOC2 locus are used. Surprisingly, no
      statistically significant linkage disequilibrium was discovered at the CKMM locus
      alone. Of the meiotic events, 84% were informative when both APO2 and CKMM loci
      were used. When studied selectively, 60% of meiotic events were informative at
      the APOC2 locus, whereas CKMM alone resulted in 65% meiotic informativeness. The
      distal marker p134C was found to have an unfortunately low information content in
      our population.

PMID- 1977685
TI  - Distal trisomy 14q. II. Molecular study of the 14q32 locus in two cases of
      chromosome 14 rearrangements with partial duplication.
AB  - Two cases of chromosome 14 rearrangements with partial duplication which occurred
      de novo were analyzed by Southern blot analysis using IGH, D14S1 and PI probes.
      In the first case, with a 46,XX,14p+ karyotype, our study confirms that the
      additional material on chromosome 14p+ results from a duplication of the 14q
      region containing the IGH, D14S1 and PI loci. In the second case, our study
      reveals only one 14q32 locus per chromosome 14 indicating that the extra material
      does not contain the 14q32 region. Our results demonstrate that molecular probes
      of the 14q32 region are valuable tools for the characterisation of chromosome 14
      abnormalities appearing de novo.

PMID- 1977686
TI  - Prenatal diagnosis of familial amyloidotic polyneuropathy: evidence for an early
      expression of the associated transthyretin methionine 30.
AB  - Transthyretin methionine 30 (TTR Met 30), which is associated with familial
      amyloidotic polyneuropathy, originates in a single base substitution (A for G) in
      the second exon of the TTR gene. This autosomal dominant disease can be diagnosed
      by RFLP analysis of NsiI-digested DNA. The amplification of DNA by PCR improves
      the diagnosis method, making it suitable for prenatal diagnosis. Using PCR
      amplified DNA, prenatal diagnosis of two at-risk fetuses was performed. Control
      Met 30 and normal DNA (either genomic or produced by site directed mutagenesis)
      were processed in parallel. The diagnosis was made by hybridization with allele
      specific oligonucleotide probes, and later confirmed by screening of the mutant
      protein in the amniotic fluid and, when possible, in the sera from the newborns.
      TTR Met 30 was detected in the amniotic fluid of a positive fetus whose father
      was the carrier of the mutation. This indicates that the mutant protein is
      expressed very early in development.

PMID- 1977687
TI  - Analysis of non-disjunction in sex chromosome tetrasomy and pentasomy.
AB  - X-linked DNA markers were used to determine the parental origin of the additional
      sex chromosomes in eight individuals with sex chromosome tetrasomy or pentasomy.
      In all cases studied, one parent contributed a single sex chromosome while the
      other parent contributed three or four sex chromosomes. Thus, it seems likely
      that most, if not all, sex chromosome tetrasomy and pentasomy is attributable to
      successive non-disjunctional events involving the same parent.

PMID- 1977689
TI  - A new HaeIII polymorphism at the D21S13 locus.
AB  - DNA markers in the pericentromeric region of human chromosome 21 have shown
      linkage to a gene for Familial Alzheimer disease (FAD; St. George Hyslop et al.
      1987). The limited informativeness of probes for the loci D21S13 and D21S16 have
      hindered precise mapping of the FAD locus and analysis of non-allelic
      heterogeneity in FAD (Schellenberg et al. 1988; St. George-Hyslop et al. 1987).
      We recently described a new EcoRII polymorphism at the D21S13 locus that was very
      informative in a large FAD pedigree (Pulst et al. 1990a,b). We now report another
      polymorphism for the D21S13 locus that further increases the informativeness of
      this locus.

PMID- 1977688
TI  - The human aminopeptidase N gene: isolation, chromosome localization, and DNA
      polymorphism analysis.
AB  - DNA encoding the human aminopeptidase N (EC 3.4.11.2) gene (PEPN) was first
      isolated using rat cDNA probes and then used in Southern analysis of DNA from
      mouse-human somatic cell hybrids to assign this gene to the long-arm region (q11
      qter) of human chromosome 15. This human genomic DNA probe detects a frequent
      DraIII polymorphism that is a useful marker for human chromosome 15.

PMID- 1977691
TI  - Alternative pathways of T-cell activation and positive clonal selection.

PMID- 1977690
TI  - Specific interactions between a human CD4+ clone and autologous CD4+ bifunctional
      immunoregulatory clones.
AB  - The cellular communications between a human CD4+ clone and autologous CD4+ clones
      induced with the first clone are described. The autoreactive clones proliferated
      after stimulation with the inducer clone, but not after stimulation with
      autologous clones expressing irrelevant specificities. The inducer clone markedly
      lost its ability to interact with the autoreactive clones after the modulation of
      its T-cell receptor. The proliferation of the autoreactive clones stimulated with
      the inducer clone was blocked by anti-DR monoclonal antibody. Collectively, these
      findings indicate that the autoreactive clones recognize idiotypic-like
      determinants on the receptor of the inducer clone in conjunction with DR antigen.
      The regulatory activity of the autoreactive clones was assayed by co-cultivation
      with their target inducer clone. The autoreactive clones were not committed to a
      single program, they could either suppress or enhance the proliferation of the
      target cells depending on the state of activation of the target cells. Activated
      target cells were suppressed whereas non-activated cells were enhanced. It is
      predicted that antagonistic cytokines released from the autoreactive clones exert
      differential effects on the target clone.

PMID- 1977692
TI  - 42nd annual conference of the Cardiological Society of India. October 24-28,
      1990. Abstracts.

PMID- 1977693
TI  - The secretory antibody response in milk and bile against fimbriae and LPS in rats
      monocolonized or immunized in the Peyer's patches with Escherichia coli.
AB  - The homing of lymphoid cells to mucosa-associated lymphoid tissue is, amongst
      other factors, influenced by the nature of the antigen used to induce an immune
      response. To study this phenomenon we have monocolonized rats with a type 1
      fimbriated Escherichia coli O6K13H1 strain and compared the secretory antibody
      response to colonization with the primary and secondary response obtained in rats
      immunized in the Peyer's patches (PP). Samples were tested with respect to the
      titres of antibodies against two antigens present on the E. coli strain: O6
      lipopolysaccharide (LPS) and type 1 fimbrial antigen. In the primary immunized
      animals, IgA anti-fimbrial antibodies were mainly seen in milk and IgA anti-LPS
      antibodies mostly found in bile. In the booster immunized, and in the
      monocolonized, animals there was a shift of the antibody response towards the
      bile. Thus anti-fimbrial antibodies appeared in milk at approximately the same or
      at a lower level than in bile and the IgA anti-LPS antibodies were almost
      completely absent in the milk. The IgG antibody response of the animals immunized
      in the PP was primarily confined to milk for both anti-LPS and anti-fimbrial
      antibodies, while the colonized animals responded with higher levels in bile than
      in milk. IgM antibodies were only seen in the milk, except in primary immunized
      animals in which biliary IgM antibodies also were found. The data illustrate
      that: (i) primary stimulated cells predestined to produce IgA anti-LPS antibodies
      home mainly to the intestine, while cells predestined to anti-fimbrial antibody
      production have a greater tendency to populate the mammary gland; (ii) after
      repeated antigen stimulation and maturation of the immune response the cells are
      directed from the mammary gland to the intestine. We thus conclude that the
      nature of the antigen and the stage of lymphocyte maturation influences the
      homing of the cells and the appearance of various antibodies in different
      secretions.

PMID- 1977695
TI  - Polymorphism in the human class I MHC locus HLA-E in Japanese.

PMID- 1977694
TI  - Characterization of the class III region in different MHC haplotypes by pulsed
      field gel electrophoresis.
AB  - The class III region of the human major histocompatibility complex (MHC) in seven
      HLA haplotypes has been analyzed using pulsed-field gel electrophoresis (PFGE),
      restriction enzymes that cut genomic DNA infrequently, and Southern blotting. In
      particular, extensive mapping with the enzyme Bss HII, which generates fragments
      in the size range 8-280 kilobases (kb), has revealed that in the haplotypes
      studied the DNA content of the class III region does not appear to vary other
      than as previously observed at the C4 and CYP21 loci.

PMID- 1977696
TI  - Thyroid stimulating hormone receptor antibody in thyroid diseases.
AB  - Thyroid stimulating hormone receptor antibody (TRA) was estimated as a measure of
      TSH binding inhibitory immunoglobulin (TBII) in 48 persons. These included (i) 14
      controls; (ii) 23 patients with Graves' disease who were tested for TRA within 3
      months of commencing treatment with carbimazole of which 13 were studied
      serially; (iii) 5 patients with toxic nodular goitre; (iv) 4 with euthyroid
      exophthalmos; and (v) 2 neonates of thyrotoxic mothers. TRA was measured with an
      RIA system, while total thyroxine (T4), free thyroxine concentration (FTC) and
      TSH were also estimated along with TRA. All controls showed undetectable TRA
      levels; 87 per cent of patients with Graves' disease were TRA positive within 3
      months of starting carbimazole therapy. In the serial study, 5 patients with
      Graves' disease who had undetectable TRA initially remained so while on
      treatment. Seven out of the remaining 8 patients showed a decline of TRA levels
      to normal over 3 to 18 months. This decline coincided with clinical and
      biochemical recovery.

PMID- 1977697
TI  - International workshop on human milk banking in developing countries.

PMID- 1977698
TI  - Nitric oxide. A novel signal transduction mechanism for transcellular
      communication.
AB  - Nitric oxide first captured the interest of biologists when this inorganic
      molecule was found to activate cytosolic guanylate cyclase and stimulate cyclic
      guanosine monophosphate (GMP) formation in mammalian cells. Further studies led
      to the finding that nitric oxide causes vascular smooth muscle relaxation and
      inhibition of platelet aggregation by mechanisms involving cyclic GMP and that
      several clinically used nitrovasodilators owe their biological actions to nitric
      oxide. Nitric oxide possesses physicochemical and pharmacological properties that
      make it an ideal candidate for a short-term regulator or modulator of vascular
      smooth muscle tone and platelet function. Nitric oxide is synthesized by various
      mammalian tissues including vascular endothelium, macrophages, neutrophils,
      hepatic Kupffer cells, adrenal tissue, cerebellum, and other tissues. Nitric
      oxide is synthesized from endogenous L-arginine by a nitric oxide synthase system
      that possesses different cofactor requirements in different cell types. The
      nitric oxide formed diffuses out of its cells of origin and into nearby target
      cells, where it binds to the heme group of cytosolic guanylate cyclase and
      thereby causes enzyme activation. This interaction represents a novel and
      widespread signal transduction mechanism that links extracellular stimuli to the
      biosynthesis of cyclic GMP in nearby target cells. The small molecular size and
      lipophilic nature of nitric oxide enable communication with nearby cells
      containing cytosolic guanylate cyclase. The extent of transcellular communication
      is limited by the short half-life of nitric oxide, thereby ensuring a localized
      response. Labile nitric oxide-generating molecules such as S-nitrosothiols may be
      involved as precursors or effectors. Further research will provide a deeper
      understanding of the biology of nitric oxide and the nature of associated
      pathophysiological states.

PMID- 1977699
TI  - Glutamine synthetase immunoreactivity is present in oligodendroglia of various
      regions of the central nervous system.
AB  - Glutamine synthetase immunoreactive oligodendrocytes were identified in the
      cerebral cortex, cerebellum, brain stem, and spinal cord. They were mostly
      confined to the gray matter, particularly close to neurons and processes. The
      white matter showed few immunoreactive oligodendroglia. It was suggested that
      some type of oligodendrocytes, specially those in perineuronal location, might
      fulfill a functional role more akin to astrocytes than to the normally
      myelinating oligodendroglia.

PMID- 1977700
TI  - Increased glutamate uptake and glutamine synthetase activity in neuronal cell
      cultures surviving chronic hypoxia.
AB  - To examine the neurochemical effects of chronic hypoxia on immature nervous
      tissue in vitro, mixed neuronal-glial cell cultures derived from fetal mice were
      exposed to 5% O2 for 24 or 48 h. Those cultures subjected to longer hypoxia
      manifested improved neuronal survival compared to those with the shorter insult,
      both with respect to neuronal morphology and also cell counts. Neurochemical
      assays were performed on living cells in situ to determine the possible basis for
      differential cell survival. After both exposure conditions. Ro5-4864-displaceable
      benzodiazepine (BDZ) binding, reflecting nonneuronal BDZ binding sites, was
      either not reduced or was elevated. Although initially reduced, binding of the
      excitatory amino acid (EAA) glutamate was progressively increased after both
      insults and, within 2 days after return to normoxia, was increased relative to
      control values (121 and 128% of controls, P less than 0.05). The most impressive
      neurochemical differences between the two conditions related to changes in the
      predominantly or exclusively glial functions of glutamate uptake and glutamine
      synthetase activity. In those cultures with relatively preserved neuronal
      morphology: 1) high affinity uptake of glutamate was elevated compared to the
      shorter hypoxic insult by 3 days of recovery (104 vs 70%, P less than 0.001) and
      2) glutamine synthetase, an enzyme localized primarily within astrocytes, was
      significantly elevated even when compared to absolute control values (148%, P
      less than 0.001). These data suggest that longer periods of hypoxia may be less
      deleterious to neurons than shorter hypoxic events because of a time-dependent
      stimulation of specific glial cell functions which relate to increased metabolism
      of potentially neurotoxic EAAs such as glutamate.

PMID- 1977701
TI  - Neuron-glial interactions involved in the regulation of glutamine synthetase.
AB  - Cocultures of rat cortical astrocytes with cerebellar granule cell neurons, but
      not a variety of other cell types tested, resulted in an induction of glutamine
      synthetase (GS) mRNA over the basal levels expressed in pure astrocyte cultures.
      This induction involved both contact- and noncontact-mediated events and may be a
      result of astroglial differentiation promoted by interactions with the primary
      neurons. Astrocytes grown in the presence of the granule neurons (but not the
      other cell types tested) exhibited a more complex, process-bearing morphology
      typical of more differentiated cells. In addition, glial cell proliferation was
      inhibited not only by the presence of live granule cells, but also by fixed
      neurons and neuronal membranes. Under the same experimental conditions, GS mRNA
      was increased (two- to threefold) compared with the expression observed in pure
      astrocyte cultures. Because of the role of GS in glutamate metabolism and the
      influence of the glutamatergic granule neurons on glial GS mRNA levels, the
      effect of exogenous glutamate was examined. The addition of 100 microM glutamate
      to the culture medium resulted in an increase in GS mRNA in the astrocyte
      cultures similar to that observed in the cocultures, where the addition of
      glutamate did not further increase GS mRNA levels. These results provide further
      evidence for the importance of neuron-glial interactions in the regulation of
      glial gene expression.

PMID- 1977702
TI  - Gastric emptying in gastroesophageal reflux and the therapeutic role of
      prokinetic agents.
AB  - The author discusses the role of prokinetic agents, such as bethanechol,
      metoclopramide, domperidone, and cisipride in the management of gastroesophageal
      reflux disease. These agents address the upper gastrointestinal motility
      disturbances that contribute to this disease and therefore have an important role
      in the acute and long-term medical management of reflux esophagitis.

PMID- 1977703
TI  - The medical management of reflux esophagitis. Role of antacids and acid
      inhibition.
AB  - Of the more than 60 million adult Americans who have heartburn at least once a
      month, 60% choose over-the-counter medication rather than consulting their
      physician. Those individuals who do seek medical advice for reflux symptoms will
      probably receive a prescription for an H2-receptor antagonist, although in many
      instances simple life-style changes and occasional use of antacids may provide
      effective therapy. Patients who have severe esophagitis or reflux symptoms
      unresponsive to H2-receptor antagonists may be treated with a more potent
      antisecretory agent (proton pump inhibitor). The author discusses the role of
      antacids and acid inhibition in the treatment of gastroesophageal reflux disease.
      The results of the clinical trials with the H2-receptor antagonists, cimetidine,
      ranitidine, famotidine, and nizatidine, and the proton pump inhibitor omeprazole,
      are compared and contrasted.

PMID- 1977704
TI  - Biological properties of factors secreted by antigen-reactive suppressor cells in
      mice infected with Mycobacterium lepraemurium.
AB  - Antigen-reactive cells were isolated from the spleens of Mycobacterium
      lepraemurium-infected C57BL/6 mice on petri dishes coated with mycobacterial
      antigens. When adoptively transferred to syngeneic mice, the mycobacterial
      antigen-reactive cells were found to depress the induction and expression of the
      delayed-type hypersensitivity (DTH) reaction to M. lepraemurium antigens. The
      adoptive transfer of soluble suppressor factors (SF) secreted by these cells
      inhibited only the expression of DTH. The cells depressing the induction of DTH
      mainly belonged to the L3T4+ (CD4+) T-lymphocyte subset, whereas those depressing
      its expression differed from the L3T4+ and Lyt-2+ (CD8+) subsets. Treatment of M.
      lepraemurium-infected mice with SF reduced their mean survival time and enhanced
      the multiplication of bacilli at the site of infection and their dissemination to
      the spleen and liver. In vitro at least, SF appeared to interfere at the level of
      mycobacterial antigen recognition by T lymphocytes rather than at the levels of
      antigen processing and presentation by macrophages.

PMID- 1977705
TI  - Gene encoding the major subunit of CS1 pili of human enterotoxigenic Escherichia
      coli.
AB  - Some enterotoxigenic strains of Escherichia coli (ETEC) utilize the CS1 pilus for
      colonization of human intestinal epithelium. We have cloned the gene which
      encodes the major CS1 subunit and called it cooA (for coli surface antigen one).
      Hybridization showed that the ETEC strain from which it was cloned carried cooA
      on a plasmid different from the one encoding its positive regulator, rns. Based
      on the cooA DNA sequence, cleavage with signal peptidase would be expected to
      produce a mature protein of 15.2 kDa; a 16-kDa polypeptide that reacted with CS1
      specific antiserum was observed on electrophoresis. At the protein level, there
      was 92% similarity and 55% identity between cooA and cfaB, the major colonization
      factor antigen I (CFA/I) antigen. However, CS1-specific antisera did not react
      with CfaB. No hybridization was seen between either of two different cooA probes
      and total DNA from ETEC strains expressing AFA-1, CFA/I, CS2, CS3, CS4, CS5, or
      CS6.

PMID- 1977706
TI  - Role of gamma interferon during infection with Plasmodium chabaudi chabaudi.
AB  - A role has been proposed for inflammatory mediators such as gamma interferon (IFN
      gamma) and reactive oxygen intermediates in the control of the blood stages of
      Plasmodium organisms. It was previously shown that IFN-gamma can be detected in
      the plasma of mice with a primary infection by Plasmodium chabaudi chabaudi (AS).
      We found that susceptible and other resistant mouse strains produced IFN-gamma,
      suggesting that susceptibility is not due to a defect in IFN-gamma production.
      Administration of IFN-gamma to intact C57BL/6 mice slightly decreased and
      partially delayed parasitemia, whereas in vivo depletion of IFN-gamma through
      injection of a "cocktail" of monoclonal antibodies against IFN-gamma exacerbated
      infection. Since CD4+ T cells are essential for the development of a protective
      immune response to P. chabaudi chabaudi, we tested whether CD4+ T cells are
      responsible for IFN-gamma production in vivo and whether exogenous IFN-gamma can
      replace the protective function of the CD4+ T cells. Mice depleted of CD4+ T
      cells were unable to produce IFN-gamma, but factors in addition to IFN-gamma may
      be important in parasite clearance.

PMID- 1977707
TI  - Combined inheritance of epithelial and erythrocyte receptors for Haemophilus
      influenzae.
AB  - Haemophilus influenzae type b expressing fimbriae showed no adherence to buccal
      epithelial cells and no agglutination of erythrocytes from three AnWj-negative
      siblings in one family. Hemagglutination of erythrocytes from 13 AnWj-positive
      members of the same family and from 24 controls was normal, and H. influenzae
      adhered well to buccal epithelial cells from them. These data indicate that the
      expression of epithelial and erythrocyte receptors for H. influenzae is inherited
      concomitantly. Combined with previous data (L. van Alphen, J. Poole, L. Geelen,
      and H. Zanen, Infect. Immun. 55:2355-2358, 1987), the results show that the
      receptor molecules on the surfaces of the epithelial cell and the erythrocyte are
      different but that the binding sites for the fimbriae of H. influenzae are
      similar.

PMID- 1977708
TI  - Cardiovascular effects of befunolol, betaxolol and timolol eye drops.
AB  - A double-blind cross-over study was carried out on 15 glaucoma patients so as to
      verify the effects of three the beta blockers, beta-1 selective betaxolol, non
      selective timolol and befunolol an agent with intrinsic sympathomimetic activity
      on the heart rate, monitored by a Holter apparatus, and with the blood pressure
      measured in standing and supine positions before and after eight days of topical
      therapy. The results showed that timolol induced a significant decrease in
      minimum heart rate (-4.2 +/- 2.9) (p less than 0.001) and in diastolic blood
      pressure in standing position (-8.0 +/- 12.5 mmHg) (p less than 0.05), betaxolol
      decreased systolic pressure in orthostatism (-7.5 +/- 12.3 mmHg) and in
      clinostatism (-12.1 +/- 16.2 mmHg) and diastolic pressure in orthostatism (-6.25
      +/- 9.4 mmHg) (p less than 0.05). Befunolol alone did not alter the heart rate or
      blood pressure.

PMID- 1977709
TI  - Acute ventilatory and gas-exchange effects of a new beta-2 agonist, broxaterol,
      in asthmatics.
AB  - The ventilatory and gas-exchange effects of broxaterol, a new selective beta 2
      adrenoceptor agonist, were investigated in ten asthmatics following intravenous
      administration of a single dose of 200 mcg. Broxaterol elicited a prompt and
      marked bronchodilating effect (increase in forced expiratory volume in one second
      and specific conductance), maintained at least up to the sixtieth minute. Minute
      ventilation and the mean expiratory flow did not increase significantly, the
      pattern of breathing showing a reduction of expiratory time, without modification
      of inspiratory time. On the other hand, occlusion pressure did not show any
      significant rise at all times of observation. Furthermore, the partial arterial
      oxygen and carbon dioxide pressures and alveolar-arterial difference in oxygen
      and physiological dead space remained unchanged, when measured at 20 min. The
      results demonstrated that broxaterol was an effective bronchodilating agent, also
      when rapidly injected, causing a prompt relief of bronchospasm. With respect to
      other beta 2-adrenoceptor agonists, this compound did not appear to increase
      minute ventilation or to induce an impairment of ventilation/perfusion ratio, at
      least after 20 min, when the bronchodilation was still evident. Finally, no side
      effects or alterations of heart rate or blood pressure were reported.

PMID- 1977710
TI  - Estrogen therapy and breast cancer.

PMID- 1977711
TI  - Contraceptive development and testing in the United States of America.
AB  - Contraceptive development, including the development of IUDs, is discussed in
      light of the changing regulatory role of the FDA. The paper considers how the FDA
      and the government affect contraceptive development. Events that led to the
      demise of IUD use in the United States probably will have long-lasting effects on
      all future contraceptive development by the pharmaceutical industry in the United
      States.

PMID- 1977712
TI  - Perlaparoscopic salpingoscopy in the evaluation of the tubal factor in infertile
      women.
AB  - Endoscopic evaluation of tubal mucosa during tubal reconstructive microsurgery
      has been shown to be an important prognostic factor in predicting the probability
      of a subsequent intrauterine pregnancy. Recent reports have described the use of
      this technique during laparoscopy in order to evaluate the tubal factor in
      infertility. We report our experience with this new diagnostic procedure. We
      utilized a flexible fiberscope with an outer diameter of 3.8 mm for endotracheal
      intubation. The fiberscope was passed through the operating channel of the
      laparoscope in order to evaluate the tubal mucosa in patients with primary and
      secondary infertility associated with tubes patent at the distal end. We
      encountered abnormalities of the infundibulum or of the ampullary mucosa in 24%
      of the tubes considered normal at HSG and in 27% of the tubes judged normal at
      laparoscopy. On the contrary, 44% of the tubes with abnormalities at HSG and 58%
      of the tubes with abnormalities at laparoscopy presented normal mucosa at
      salpingoscopy. Our results, in addition to those published in the literature,
      demonstrate that salpingoscopy is an important and valuable diagnostic procedure
      for an accurate evaluation of infertile patients. With this technique it is also
      possible to select patients with a favorable prognosis for tubal microsurgery.

PMID- 1977713
TI  - An in vivo technique for screening immunologic factors in the etiology of the
      unexplained poor postcoital test.
AB  - A study was designed to determine the incidence and etiology of the unexplained
      poor postcoital test. An in vivo comparison of sperm penetration by husband's
      versus donor sperm in the wife's estrogen-stimulated mucus was performed. The 8
      of 30 women showing improvement of husband's penetration in mucus (group 1) were
      treated with high-dose estrogen (HDE) and hMG, and 4/8 conceived. Anti-sperm
      antibodies (ASA) were insignificant in this group. In group 2, in which donor
      sperm penetrated but husband's sperm did not, 8 men of 17 were found to have an
      ASA level over 50% on the sperm surface; 6/8 treated with high-dose
      methylprednisolone (MP) had an improved postcoital test, and 5 achieved a
      pregnancy. Two patients with levels under 50% were still treated with MP, and one
      achieved a pregnancy. In five group-3 couples, positive ASA were found in the
      cervical mucus of two women; and one woman improved on the postcoital test and
      conceived following MP therapy. The 30 unexplained poor postcoital tests occurred
      in 5,000 couples evaluated. In general, those patients considered to have
      significant clinical antibody had levels over 50%. Because side effects of MP may
      be severe, and positive ASA may be found in normal donors, it is important to use
      a comparison penetration test to help determine if treatment with corticosteroids
      seems reasonable.

PMID- 1977714
TI  - Psychosexual problems of infertile women in India.
AB  - Female partners of 200 infertile couples have been interviewed for psychosexual
      problems. There were 105 women who complained of one sexual problem or more.
      Decreased frequency of intercourse and anorgasmia in wife were the most common
      problems identified. A significant number of husbands considered the testing of
      semen along with scheduled coitus to be a problem. These problems appear to be
      related to the feeling of being infertile rather than any social or personal
      factors, such as age, education, or income. The majority of the women welcomed
      this in-depth interview for sexual problems.

PMID- 1977715
TI  - Prognostic potential of serum CA 125 levels in danazol-treated patients with
      external endometriosis: a preliminary study.
AB  - Serum levels of CA 125 in 33 patients with progressive external endometriosis who
      were treated with 400 mg/day of Danazol for 16 weeks were assayed for an extended
      period (24-40 weeks), and changes in the CA 125 pattern were analyzed. Patterns
      of hormonal response were classified into four types. Prognosis for one type was
      good, whereas that for the other three types was poor. By making use of these
      patterns, we were able to determine more accurately the proper dose of Danazol,
      to alter the duration of treatment, and to predict relapse.

PMID- 1977716
TI  - Adrenal hyperresponsiveness to ACTH stimulation in women with polycystic ovary
      syndrome: an adrenarchal type of response.
AB  - Adrenal responsiveness to ACTH stimulation (1 mg, i.m.) was assessed by measuring
      cortisol (Cort) and 17-hydroxyprogesterone (17OHP) at 0, 30, 60, and 90 minutes
      and progesterone (P), dehydroepiandrosterone (DHEA), dehydroepiandrosterone
      sulfate (DHEA-S), delta 4-androstenedione (delta 4A), and testosterone (T) at 0,
      60, and 90 minutes post-ACTH in 30 women with polycystic ovary syndrome (PCO).
      The results were compared with those from 12 normally menstruating women. Three
      distinct patterns of responses of the adrenal steroids were observed in PCO
      patients, while cortisol response was similar to that of normal controls: (a)
      normal responders (n = 9, 30% of PCO patients), in whom a delta max response
      similar to that of normals was observed, although basal delta 4A and T levels
      were found to be elevated; (b) 21-OH dysfunction group (n = 6, 16.6%), in whom
      delta max 17OHP levels and delta max 17OHP to delta max Cort ratio were
      significantly higher than those of normals and the other PCO groups, indicating a
      dysfunction at the 21-hydroxylase level; (c) adrenarchal type of response group
      (n = 16, 53%), in whom statistically significant (P less than .0001)
      hyperresponsiveness of DHEA and, in 11 of them, of delta 4A, with high delta max
      delta 4A to delta max DHEA to delta max Cort ratios were found, indicative of a
      selective overproduction of the steroids during steroidogenesis. Moreover, the
      significantly higher delta max delta 4A to delta max 17OHP ratio found in group c
      is a further indication of increased 17,20-lyase efficiency, as is encountered
      during adrenarche.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1977717
TI  - Relationship of a human oocyte scoring system to oocyte maturity and fertilizing
      capacity.
AB  - A simple, quick, and semiquantitative human oocyte scoring system is described.
      Oocyte-corona-cumulus complexes were spread, either by tilting the dish or by
      aspiration of the fluid, and examined under the dissecting microscope. A maximum
      of four points was assigned to each of the following: cumulus expansion, cumulus
      appearance, amount of cumulus, corona expansion, corona appearance, and oocyte
      appearance. The oocyte score was significantly correlated to two important
      physiological parameters of oocytes, nuclear maturity (P less than .02) and
      fertilization rate (P less than .0001). This oocyte scoring system is useful for
      selecting oocytes for in vitro fertilization and embryo transfer (IVF-ET) or
      gamete intrafallopian tube transfer (GIFT), for training new laboratory personnel
      in recognizing the important characteristics of a mature oocyte, and in the
      standardized reporting of oocyte quality by different IVF-ET or GIFT programs.

PMID- 1977718
TI  - Effects of passive motion and early vs. delayed ambulation on adhesion formation
      in rat uterine surgery.
AB  - The goal of our study was to assess the effects of unrestrained ambulation and of
      passive motion and delayed ambulation on the occurrence of adhesions after
      controlled uterine injuries, produced by conventional surgical techniques, in
      rats. A classic Pomeroy ligation was performed on the left uterine horn and a 1
      cm x 3 mm rectangular flap hysterotomy on the right uterine horn in 48 rats,
      which were subsequently divided into four groups of 12 each. Group 1 served as
      controls and were allowed to ambulate without restriction following recovery from
      the anesthetic. Group 2 remained anesthetized for 12 hours, during which time
      each was passively moved from one lateral decubitus position to the opposite
      every 15 minutes. Group 3 were anesthetized for 12 hours and group 4 animals for
      24 hours, following which unrestricted ambulation was allowed. All animals were
      killed 3 weeks after the operation and the left and right uterine horn adhesions
      were graded separately using a macroscopic system. The adhesion score of the left
      horn in group 2 animals (3.5) was significantly higher (P less than .025) than in
      the control animals (2.25). Group 3 animals had adhesion scores on the left
      (2.75), but did not differ significantly from controls (P greater than .05).
      Group 4 animals demonstrated significantly higher adhesion scores of the left
      uterine horn (3.3) than control animals. Group 2 animals, but not group 3 or
      group 4, had higher mean adhesion scores of the right uterine horn than control
      animals (P less than .005).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1977719
TI  - Fructose, prostatic acid phosphatase and zinc levels in the seminal plasma of
      varicoceles.
AB  - The function of sex accessory glands in 95 varicocele patients was investigated
      by determining the fructose, prostatic acid phosphatase (PAP), and zinc levels in
      the seminal plasma. These biochemical substances are, in fact, markers of the
      seminal vesicles and prostate, respectively. It was observed that both the PAP
      and zinc levels were significantly lower (P less than .002) in varicoceles than
      in the control group, while both fructose and PAP levels were particularly low in
      a small subgroup of the older patients. The authors suggest that the impaired sex
      accessory gland functions could arise from decreased venous drainage in the
      vesico-prostatic plexus. The fructose/zinc ratio appears to be negatively related
      to sperm motility (r = .31, P = .01); this suggests that in varicocele the
      impaired sex accessory gland secretions could themselves influence the motility
      of ejaculated spermatozoa.

PMID- 1977721
TI  - Plasma free fatty acid concentration during hyperglycemic glucose clamp with and
      without somatostatin infusion in obese subjects with normal glucose tolerance.
AB  - In the present study we evaluated the regulation of plasma free fatty acid (FFA)
      concentration by glucose and insulin in human obesity. To this purpose we
      measured plasma FFA concentration in normoglycemic, normoinsulinemic obese (n =
      8) and nonobese (n = 8) healthy subjects during 240 min of exogenous
      hyperglycemia (hyperglycemic glucose clamp) in presence of both glucose
      stimulated (0-120 min and 180-240 min) and somatostatin-inhibited (120-180 min)
      insulin secretion. We found that plasma FFA curves were roughly parallel in the 0
      120 min period and FFA values of obese subjects were constantly higher throughout
      the experimental period. Moreover, the difference between the two groups was
      significant when individual data were expressed as a percent of fasting FFA value
      (P less than 0.0001 from 0 to 120 min). Plasma insulin levels were similar in the
      two groups during the entire study. The amount of glucose metabolized during the
      80-120 min period was significantly lower in obese than in nonobese subjects (172
      +/- 7 v. 341 +/- 11 mg/m2.min, P less than 0.01; means +/- s.e.). During the
      somatostatin period (120-180 min) plasma insulin was lowered close to basal
      values in both groups (116 +/- 15 and 109 +/- 11 pmol/l) and plasma FFA
      concentrations rose in a linear fashion. Our data suggest that suppression of
      plasma FFA concentrations by glucose and insulin is qualitatively similar in
      healthy nonobese and obese subjects, the latter having higher FFA values. Insulin
      action on FFA metabolism isn ot grossly impaired in obese subjects who are
      clearly insulin resistant as far as glucose metabolism is concerned.

PMID- 1977720
TI  - Amino sugar levels in normally coagulating and poorly coagulating human
      ejaculates.
AB  - Free and total amino sugar levels were determined in human prostatic fluid,
      vasectomized semen, presumably fertile semen, and in ejaculates having different
      degrees of coagulation. About 87% of the total amino sugar in seminal plasma was
      found in the bound form. The seminal vesicles were the richest source for seminal
      amino sugar, being followed by the prostate, while the epididymes contributed
      negligibly, if at all. Total amino sugar level of the poorly coagulating
      ejaculates was found to be significantly lower than those of the vasectomized,
      presumably fertile, and normally coagulating ejaculates. The degree of
      coagulation and the amino sugar level of human ejaculates were related by a
      correlation coefficient of .468 (n = 60; P less than .001).

PMID- 1977723
TI  - Energy expenditure and obesity. A symposium held at the 5th annual NAASO
      Conference. Banff, 1988. Proceedings.

PMID- 1977722
TI  - Increased brain 3H-paraminoclonidine (alpha 2-adrenoceptor) binding associated
      with perpetuation of diet-induced obesity in rats.
AB  - Brain alpha-adrenoceptor (alpha-AR) binding was examined as a possible
      explanation for the persistence of diet-induced obesity (DIO) or resistance (DR)
      in rats after they were returned to chow from a high-energy, fat and sucrose diet
      (CM diet). Adult Sprague-Dawley rats (n = 28) were fed the CM diet for 12 weeks.
      Those that gained more weight than chow-fed controls were classified as DIO and
      those that gained the same weight as controls were called DR. The 10 heaviest DIO
      and 8 lightest DR rats were then placed on chow for an additional 14 weeks. After
      the entire 26-week period, the body weights of DIO rats were still 21 per cent
      greater and those of the DR rats were 9 per cent less than 7 chow-fed controls.
      DIO retroperitoneal fat pads were also 62 per cent heavier while DR pads were
      equal to controls. Plasma insulin and glucose levels were comparable in all 3
      groups. Receptor autoradiographic studies of brain alpha 1-AR (3H prazosin; PRZ)
      and alpha 2-AR (3H-paraminoclonidine; PAC) adrenoceptor binding were carried out
      using these animals at the end of 26 weeks. Binding to alpha 1-AR was comparable
      in all groups but alpha 2-AR binding was 47-103 per cent higher in DIO compared
      to DR and chow-fed controls in 14 of 17 brain areas assessed. These included the
      dorsomedial, ventromedial and paraventricular hypothalamic n. and all amygdalar
      areas. Such widespread differences in alpha 2-AR binding in rats fed the same
      diet but of differing body weights suggest that alpha 2-AR binding is a marker
      for differences in body weight regulation and may be important in the control of
      the differences in weight gain.

PMID- 1977724
TI  - Further Rome congress papers. Presented at the 36th International
      Psychoanalytical Congress. Rome, July 1989. Proceedings.

PMID- 1977725
TI  - Sulphasalazine induced agranulocytosis in a patient with rheumatoid arthritis.

PMID- 1977726
TI  - Zollinger-Ellison syndrome: methods of diagnosis and treatment.
AB  - Until two decades ago the Zollinger-Ellison syndrome (ZES) was difficult to
      diagnose and stage accurately. Total gastrectomy was often the ultimate
      treatment. Improvements in the measurement of serum gastrin and in radiographic
      imaging have greatly improved the precision of diagnosis and staging. Treatment
      with histamine-2 receptor antagonists and proton pump blockers have eliminated
      the need for gastrectomy, and current surgical intervention is directed at cure
      through removal of the localized gastrinoma. We reviewed the management of eight
      patients with this diagnosis seen at Henry Ford Hospital from 1983 to 1988. Time
      from first presentation to diagnosis varied from two months to ten years (mean
      4.5 years) and four patients had peptic ulcer surgery before the ZES diagnosis. A
      high level of suspicion is required in order to make early diagnosis. Prior to
      elective peptic ulcer surgery, all patients should have serum gastrin assay to
      exclude ZES.

PMID- 1977727
TI  - Phenylethanolamine N-methyltransferase-(PNMT)-like immunoreactivity in the rat
      parathyroid gland.
AB  - A phenylethanolamine N-methyltransferase-(PNMT)-immunoreactivity, present without
      the other catecholamine-synthesizing enzymes tyrosine hydroxylase (TH) and
      dopamine-beta-hydroxylase (DBH), has been previously detected in the central
      nervous system and in endocrine cells of the islets of Langerhans and the
      pituitary intermediate lobe of the rat. In the present study a similar PNMT-like
      immunoreactivity is demonstrated in the rat parathyroid gland. The
      immunoreactivity was distinctly localized to the cell periphery, and present in
      all glandular cells. The thyroid gland was negative. In the parathyroid TH- and
      DBH-immunoreactivity was seen only in vascular nerve fibers; no glandular cells
      were stained. The functional significance of the PNMT-like immunoreactivity is
      not known. The absence of TH- and DBH-immunoreactivity and the low level of
      adrenaline detected in the parathyroid, and the peripheral localization of the
      immunoreactivity may indicate an alternative enzyme function or the detection of
      an immunologically related protein common to pancreatic, pituitary and
      parathyroid endocrine cells.

PMID- 1977728
TI  - Reversal by two dihydropyridine compounds of resistance to multiple anticancer
      agents in mouse P388 leukemia in vivo and in vitro.
AB  - We investigated whether two representative 1,4-dihydropyridine derivatives, NK
      250 and NK-252, could potentiate the antitumor activity of multiple anticancer
      agents including vincristine (VCR), vinblastine, vindesine and actinomycin D in
      drug-resistant tumor cells and their parental drug-sensitive tumor cells. NK-250
      and NK-252 at 5-10 microM almost completely reversed VCR resistance in cultured
      VCR-resistant P388/VCR cells derived from the mouse drug-sensitive P388/S
      leukemia cell line and also potentiated the cytocidal activity of VCR in drug
      sensitive P388/S cells. NK-250 and NK-252 at 1-10 microM inhibited the
      photoaffinity labeling by [3H]azidopine of the cell-surface 170,000-molecular
      weight P-glycoprotein. In chemotherapeutic experiments with leukemia-bearing
      mice, NK-250 or NK-252 was orally administered in combination with different
      drugs of the MDR phenotype administered intraperitoneally. The antitumor activity
      of the various combinations was found to be augmented in mice bearing P388/S- and
      P388/VCR-leukemia. Among the combinations examined, the combination of NK-250 and
      VCR was the most effective. These two 1,4-dihydropyridines, NK-250 and NK-252,
      are unique compounds because they were effective not only in circumventing the
      drug resistance, but also in potentiating the action of antitumor drugs against
      drug-sensitive tumors.

PMID- 1977729
TI  - Correlation between the presence of microvilli and the growth or metastatic
      potential of tumor cells.
AB  - We used an electron microscope to examine microvilli which appear on the surfaces
      of various tumor cells with high or low growth potential and/or metastatic
      ability. The results show that a greater number of microvilli appeared on the
      surfaces of tumor cells (QRpP and ERpP) which possess high growth potential than
      on tumor cells (QR and ER) with low growth potential. We also observed that
      microvilli were more abundant on the surface of highly metastatic clone cells,
      i.e. c-SST-2 (cl-2), mouse B16 melanoma (F-10) and human colon carcinoma (KM12SM)
      than on weakly metastatic clone cells, c-SST-2 (cl-4-2), B16 (F-1) and (KM12C).
      At the same time, more microvilli were observed on the surface of B16 BL6 cells,
      which were obtained from the metastatic site of the B16 F10 cells, than on the
      surface of the parent B16 F10 cells. Immunoelectron microscopy revealed that the
      c-neu oncogene product, which is closely related to an epidermal growth factor
      receptor, was positively stained in the microvilli of tumor cells (ERpP) with
      high growth potential and high metastatic ability, whereas the tumor cells (ER)
      with low growth potential and weak metastatic ability were not stained. These
      findings suggest that the increased presence of microvilli correlates closely
      with the growth potential and metastatic ability of tumor cells.

PMID- 1977731
TI  - Beta-blockade with intrinsic sympathetic activity modifies favorably exercise
      induced changes in plasma lipoproteins.
AB  - The effects of beta-blockade on acute exercise-induced changes in plasma
      lipoprotein levels were investigated in 12 healthy normotensive subjects by use
      of beta-blockers of three types: a nonselective agent, a beta 1-selective agent,
      and a nonselective agent with intrinsic sympathomimetic activity (ISA) or partial
      agonist activity. Each subject received each drug and a placebo for 1 wk each
      according to a randomized double-blind crossover design. After placebo, exercise
      caused 10-20% increases in total plasma cholesterol and the high-density
      lipoprotein (HDL)-cholesterol fraction. The total-to-HDL cholesterol ratio fell,
      particularly during the 30-min recovery phase. Pindolol treatment increased
      resting values of HDL cholesterol (from 43 +/- 4 to 48 +/- 4 mg/dl) and
      potentiated the response to exercise (to 59 +/- 5 vs. 51 +/- 4 mg/dl after
      placebo). The total-to-HDL cholesterol ratio was significantly lower after
      pindolol treatment than after placebo. In contrast, neither atenolol nor timolol
      affected exercise-induced changes in plasma lipoprotein levels. The effects of
      pindolol on other study parameters (exercise endurance and exercise-induced
      increases in systolic blood pressure, heart rate, and potassium) were similar to
      the effects of the nonselective agent, timolol. We conclude that the effects of
      pindolol on the plasma lipid profile are due to its ISA and that the process
      activated (possibly plasma lecithin-cholesterol acyltransferase activity) is
      under minimal sympathetic control and, therefore, sensitive to the expression of
      ISA both at rest and in response to exercise.

PMID- 1977732
TI  - Differences in enzymatic and mechanical isolated rabbit renal proximal tubules:
      comparison in long-term incubation.
AB  - Suspensions of renal proximal tubules (RPT) are the in vitro model for many
      biochemical and physiologic investigations. Inasmuch as there are numerous
      procedures for tubule isolation and the more commonly used enzymatic procedures
      may disrupt the basement membrane, there is a need for information comparing the
      influence of various isolation methods on RPT viability and function in long-term
      suspension. Rabbit RPT isolated a) enzymatically (ENZ) by in vitro collagenase
      digestion and Percoll size and density purification, and b) mechanically (MECH)
      by in vitro iron oxide perfusion and purification by sieving and magnetic removal
      of glomeruli were compared for viability, morphology, and functional stability
      during long-term suspension. RPT isolated by ENZ and MECH methods had excellent
      viability (less than 15% lactate dehydrogenase release), limited lipid
      peroxidation (less than 0.2 nmol MDA.mg protein-1), and stable nystatin
      stimulated oxygen consumption (QO2) (38 and 36 nmol O2.mg protein-1.min-1)
      throughout 24 h of incubation. Basal QO2 was higher in ENZ than MECH tubules (27
      and 19 nmol O2.mg protein-1.min-1, respectively), and was unchanged over 24 h in
      each preparation. The higher basal QO2 in ENZ tubules was ouabain-sensitive,
      suggesting an increased rate of Na+,K(+)-ATPase activity in these tubules. Total
      glutathione content (oxidized + reduced) in ENZ and MECH tubules increased over
      the 24-h incubation from 8 to 18 nmol.mg protein-1. gamma-Glutamyltranspeptidase
      (GGT) activity of the RPT homogenates was equivalent in both preparations and
      stable over time. The ratio of suspension GGT activity to homogenate GGT activity
      doubled (0.4 to 0.8) during the incubation period. MECH tubules retained their
      tubule structure during 24 h of incubation whereas the ENZ tubules had a striking
      loss of tubular morphology over time. These results show that ENZ- and MECH
      isolated renal proximal tubule suspensions exhibit similar biochemical properties
      in long-term incubations but differ in ouabain-sensitive QO2 and the retention of
      tubular morphology. The loss of tubular morphology and the increase in the rate
      of Na+,K(+)-ATPase activity in ENZ tubules may be secondary to the disruption of
      the tubular basement membrane.

PMID- 1977730
TI  - In situ localization of the human multidrug-resistance gene mRNA using thymine
      thymine dimerized single-stranded cDNA.
AB  - In order to detect the mRNA transcribed from the multidrug-resistance gene
      (MDR1), thymine-thymine (T-T) dimerized single-stranded DNA probes have been
      utilized for hybridization with mRNA either on nitrocellulose filters or in cells
      and tissues. S1 nuclease digestion rather than sonication was used to obtain
      short T-T dimerized single-stranded DNA (300-400 bases) so that they could
      penetrate well into the cytoplasm. The hybridized T-T DNA was detected
      immunohistochemically using rabbit anti-T-T DNA antibody (Ab) and peroxidase
      labeled goat anti-rabbit IgG Ab. Employing this system, MDR1 mRNA could be
      localized clearly in the human multidrug-resistant cell lines K562/ADM, CEM/VLB,
      2780AD, and KBC4 cells as well as in human fetal kidney and gastric carcinoma.
      Furthermore, our system successfully detected the expression of MDR1 mRNA in cell
      lines of increasing resistance. These results paralleled results obtained at the
      protein level by immunohistochemistry. The analysis of MDR1 RNA expression by
      this in situ hybridization technique should be useful in the study of normal
      human tissues and tumor samples expressing the MDR1 gene.

PMID- 1977734
TI  - Hemodynamic effects of somatostatin in the rat: relationship with plasma glucagon
      levels.
AB  - Hepatic, splanchnic, and systemic hemodynamic effects of somatostatin infusion,
      as well as changes in plasma glucagon concentration, were studied in normal rats,
      using techniques involving radioactive microspheres and radioimmunoassay.
      Somatostatin infusion caused a decrease in arterial blood flow to the stomach,
      small intestine and spleen, with the net effect of reducing hepatic portal blood
      flow and portal pressure. The hepatic arterial blood flow was not altered. The
      systemic hemodynamic effects of somatostatin were slight, although renal blood
      flow diminished, Plasma glucagon concentration did not vary immediately after
      somatostatin infusion. The mechanism of the hemodynamic action of the hormone is
      not yet clear, but in normal conditions it is not related to the inhibition of
      glucagon secretion.

PMID- 1977733
TI  - Perfusion-time dependent enhancements of guanabenz- and KCl-induced
      vasoconstrictions in isolated and perfused dog pulmonary veins.
AB  - The responses of the isolated canine pulmonary vein to guanabenz and to potassium
      chloride (KCl) were examined by means of the cannula-inserting method. The vessel
      was perfused by Krebs-Ringer bicarbonate solution at a constant flow rate at 37
      degrees C. In the early stage (within 2-3 hours of the perfusion period),
      guanabenz induced a dose-dependent vasoconstriction, whereas high doses of KCl
      caused, at most, a slight vasoconstriction. At the late stage (within 8-11 hours
      of the perfusion period), the dose-response curve for guanabenz was shifted to
      the left and the maximum response became approximately 3-fold larger than that in
      the early stage. Vasoconstriction in response to KCl was observed in 8 out of 11
      preparations (73%) in the late stage. In both early and late stages, guanabenz
      induced responses were similarly antagonized by DG-5128 (a selective alpha 2
      adrenoceptor antagonist) but not by bunazosin (a selective alpha 1-adrenoceptor
      antagonist). Diltiazem caused an inhibition of guanabenz-induced constrictions,
      particularly in the late stage. KCl-induced vasoconstriction was not affected by
      bunazosin or DG-5128, but was markedly suppressed by diltiazem. In preparations
      in which the endothelium was removed by intraluminal treatment with saponin, the
      changes in guanabenz- and KCl-induced responses, which were dependent on the
      perfusion time, were not modified in either stage. Our results suggest that alpha
      2-adrenoceptor-mediated vasoconstriction is enhanced in a perfusion-time
      dependent manner in the isolated and perfused canine pulmonary vein. These
      enhanced responses mediated by latent alpha 2-adrenoceptors are dependent on the
      influx of extracellular calcium ions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1977735
TI  - Genes on the 90-kilobase plasmid of Salmonella typhimurium confer low-affinity
      cobalamin transport: relationship to fimbria biosynthesis genes.
AB  - A cloned fragment of Salmonella typhimurium DNA complemented the defect in
      cobalamin uptake of Escherichia coli or S. typhimurium btuB mutants, which lack
      the outer membrane high-affinity transport protein. This DNA fragment did not
      carry btuB and was derived from the 90-kb plasmid resident in S. typhimurium
      strains. The cobalamin transport activity engendered by this plasmid had
      substantially lower affinity and activity than that conferred by btuB.
      Complementation behavior and maxicell analyses of transposon insertions showed
      that the cloned fragment encoded five polypeptides, at least two of which were
      required for complementation activity. The nucleotide sequence of the coding
      region for one of these polypeptides, an outer membrane protein of about 84,000
      Da, was determined. The deduced polypeptide had properties typical of outer
      membrane proteins, with an N-terminal signal sequence and a predicted
      preponderance of beta structure. This outer membrane protein had extensive amino
      acid sequence homology with PapC and FaeD, two E. coli outer membrane proteins
      involved in the export and assembly of pilus and fimbria subunits on the cell
      surface. This homology raises the likelihood that the observed cobalamin
      transport did not result from the production of an authentic transport system but
      that overexpression of one or more outer membrane proteins allowed leakage of
      cobalamins through the perturbed outer membrane. These results also suggest that
      the 90-kb plasmid carries genes encoding an adherence mechanism.

PMID- 1977736
TI  - Isolation and characterization of mutants with lesions affecting pellicle
      formation and erythrocyte agglutination by type 1 piliated Escherichia coli.
AB  - The product of the pilE (also called fimH) gene is a minor component of type 1
      pili in Escherichia coli. Mutants that have insertions in the pilE gene are fully
      piliated but unable to bind to and agglutinate guinea pig erythrocytes, a
      characteristic of wild-type type 1 piliated E. coli. In this paper we describe
      the isolation of 48 mutants with point lesions that map to the pilE gene. Such
      mutants were isolated by using mutT mutagenesis and an enrichment procedure
      devised to favor the growth of individuals that could form a pellicle in static
      broth containing alpha-methylmannoside, an inhibitor of erythrocyte binding and
      pellicle formation. Results indicated that the enrichment favored mutants
      expressing pilE gene products that were defective in mediating erythrocyte
      binding. Characterization of 12 of the mutants in greater detail revealed that
      certain lesions affected pilus number and length. In addition, a mutant that was
      temperature sensitive for erythrocyte binding was isolated and used to provide
      evidence that pellicle formation relies on the intercellular interaction of pilE
      gene products. Our results suggest a molecular explanation for the old and
      paradoxical observations connecting pellicle formation and erythrocyte
      agglutination by type 1 piliated E. coli.

PMID- 1977737
TI  - Molecular analysis of the Azotobacter vinelandii glnA gene encoding glutamine
      synthetase.
AB  - The gene encoding glutamine synthetase (GS), glnA, was cloned from Azotobacter
      vinelandii on a 6-kb EcoRI fragment that also carries the ntrBC genes. The DNA
      sequence of 1,952 bp including the GS-coding region was determined. An open
      reading frame of 467 amino acids indicated a gene product of Mr 51,747.
      Transcription of glnA occurred from a C residue located 32 bases upstream of an
      ATG considered to be the initiator codon because (i) it had a nearby potential
      ribosome-binding site and (ii) an open reading frame translated from this site
      indicated good N-terminal homology to 10 other procaryotic GSs. Sequences similar
      to the consensus RNA polymerase recognition sites at -10 and -35 were present at
      the appropriate distance upstream of the transcription initiation site. As
      expected from earlier genetic studies indicating that expression of A. vinelandii
      glnA did not depend on the rpoN (ntrA; sigma 54) gene product, no sigma 54
      recognition sequences were present, nor was there significant regulation of glnA
      expression by fixed nitrogen. Repeated attempts to construct glutamine auxotrophs
      by recombination of glnA insertion mutations were unsuccessful, Although the
      mutated DNA could be found by hybridization experiments in drug-resistant A.
      vinelandii transformants, the wild-type glnA region was always present. These
      results suggest that glnA mutations are lethal in A. vinelandii. In
      [14C]glutamine uptake experiments, very little glutamine was incorporated into
      cells, suggesting that glutamine auxotrophs are nonviable because they cannot be
      supplied with sufficient glutamine to support growth.

PMID- 1977739
TI  - Postural hypotension in chronically medicated schizophrenics.
AB  - Blood pressure readings at rest and on standing in 196 chronic schizophrenic
      patients on stable long-term antipsychotic treatment were compared with those in
      unmedicated healthy controls. Patients recorded significantly lower resting blood
      pressure and significantly higher prevalence of postural hypotension than
      controls. The prevalence of postural hypotension in patients was 77% at 1 minute
      and 16.8% at 3 minutes after standing compared with absence of postural
      hypotension in controls at both time points. Prevalence of postural hypotension
      was unaffected by age or sex and was poorly correlated with drug dose, except in
      young patients. alpha 1-Receptor binding affinity of antipsychotic drugs was not
      predictive of postural hypotension. The possible significance of such persistent
      postural hypotension in chronically medicated patients is discussed.

PMID- 1977738
TI  - Cloning of an aroF allele encoding a tyrosine-insensitive 3-deoxy-D-arabino
      heptulosonate 7-phosphate synthase.
AB  - In Escherichia coli, genes aroF+, aroG+, and aroH+ encode isoenzymes of 3-deoxy-D
      arabino-heptulosonate 7-phosphate synthases that are feedback inhibited by
      tyrosine, phenylalanine, and tryptophan, respectively. A single base pair change
      in aroF causes a Pro-148-to-Leu-148 substitution and results in a tyrosine
      insensitive enzyme.

PMID- 1977740
TI  - Valproate use in the older manic patient.
AB  - The authors present a case series of seven older (mean age = 66 years) state
      hospital patients treated with valproate as an adjunct to conventional
      medications. The patients had had affective disorder (chiefly bipolar disorder)
      for an average of 31 years. Most had been hospitalized at the state hospital for
      several years. Previous unsuccessful treatments had included lithium,
      carbamazepine, antipsychotics, benzodiazepines, and antidepressants and
      electroconvulsive therapy in one patient. After 1 month of adjunctive treatment,
      valproate led to marked improvement in three patients, moderate improvement in
      two, minimal improvement in one, and no change in one patient with delusional
      depression. Global Assessment Scale scores increased over baseline an average of
      29 points (p = .01). Valproate proved to be safe in these older individuals, many
      of whom had several medical conditions.

PMID- 1977741
TI  - Is relapse a justification for the use of high-dose antipsychotics?

PMID- 1977742
TI  - Targeting treatment in patients with mixed symptoms of anxiety and depression.
AB  - Patients with major depression often exhibit clinical anxiety. Although not
      included among DSM-III-R criteria for major depression, clinical anxiety may be
      the most important symptom to assess in planning the treatment for this affective
      disorder. By actively treating the anxiety component, psychiatrists can modify
      serious suicide risk factors in some patients and provide the immediate benefits
      that will induce others to comply with antidepressant therapy.

PMID- 1977743
TI  - Temperature-sensitive mutant of Bacillus subtilis glutamine synthetase obtained
      by random mutation.
AB  - Random mutations were introduced into the B. subtilis glutamine synthetase gene
      by using nitrous acid, and a high temperature-sensitive mutant was selected. DNA
      sequencing of the restriction fragment containing the mutation revealed a single
      base-pair change resulting in the substitution of Leu 318 with Phe. The mutant
      enzyme was purified, and its kinetic and physical properties were characterized.
      The Mg2(+)-dependent activity and Mg2+ plus Mn2(+)-dependent activity of the
      mutant were less than 5% of those of the wild-type at 37 degrees C, and these
      activities decreased above 15 degrees C, whereas the Mn2(+)-dependent activity
      was nearly normal. Affinity of the mutant enzyme for glutamate was extremely
      decreased although the Km values for NH3 or ATP were almost the same as those of
      the wild-type. The mutant enzyme was more susceptible than the wild-type enzyme
      to digestion with chymotrypsin in the presence of glutamate, ATP, and Mg2+,
      although addition of glutamate, ATP, and Mn2+ completely protected both enzymes.
      These results and circular dichroism analyses suggested that Leu 318 is at the
      glutamate-binding site and that the substitution of Leu 318 for Phe reduces the
      ability of the enzyme to form the enzyme-substrate complex, probably supported by
      Mg2+.

PMID- 1977745
TI  - Progesterone photoaffinity labels P-glycoprotein in multidrug-resistant human
      leukemic lymphoblasts.
AB  - We show for the first time that [3H]progesterone ([3H]PRG) can directly
      photoaffinity label membrane proteins prepared from a multidrug-resistant human
      leukemic lymphoblastic cell line CEM/VLB5K. A 170-kDa protein in CEM/VLB5K cell
      membranes was specifically labeled by [3H]PRG, which we identified as P
      glycoprotein (Pgp) by immunoprecipitation with monoclonal antibody C219. The
      anticancer drug vinblastine and multidrug resistance reversing agent verapamil as
      well as several steroidal hormones were examined for their ability to interfere
      with [3H]PRG binding to Pgp. We found that 200-fold molar excess of vinblastine
      strongly inhibited (93%) the binding of [3H]PRG to Pgp compared with verapamil
      (80%), progesterone (78%), testosterone (46%), dexamethasone (25%), and
      aldosterone (56%). The results of this study provide direct evidence that
      progesterone can bind to Pgp and support the hypothesis that under physiological
      conditions Pgp may play a role in the excretion of progesterone from certain
      cells. Importantly, our results show that under our conditions vinblastine and
      verapamil are better able to compete with [3H]PRG for binding to Pgp than are
      other steroids, including testosterone, corticosteroids, and mineralocorticoids.

PMID- 1977746
TI  - Structural and catalytic properties of copper in lysyl oxidase.
AB  - The spectral and catalytic properties of the copper cofactor in highly purified
      bovine aortic lysyl oxidase have been examined. As isolated, various preparations
      of purified lysyl oxidase are associated with 5-9 loosely bound copper atoms per
      molecule of enzyme which are removed by dialysis against EDTA. The enzyme also
      contains 0.99 +/- 0.10 g atom of tightly bound copper per 32-kDa monomer which is
      not removed by this treatment. The copper-free apoenzyme, prepared by dialysis of
      lysyl oxidase against alpha,alpha'-dipyridyl in 6 M urea, catalyzed neither the
      oxidative turnover of amine substrates nor the anaerobic production of aldehyde
      at levels stoichiometric with enzyme active site content, thus contrasting with
      the ping pong metalloenzyme. Moreover, the spectrum of the apoenzyme was not
      measurably perturbed upon anaerobic incubation with n-butylamine, while
      difference absorption bands were generated at 250 and 308 nm in the spectrum of
      the metalloenzyme incubated under the same conditions. A difference absorption
      band also developed at 300-310 nm upon anaerobic incubation of pyrroloquinoline
      quinone, the putative carbonyl cofactor of lysyl oxidase, with n-butylamine. Full
      restoration of catalytic activity occurred upon the reconstitution of the
      apoenzyme with 1 g atom of copper/32-kDa monomer, whereas identical treatment of
      the apoenzyme with divalent salts of zinc, cobalt, iron, mercury, magnesium, or
      cadmium failed to restore catalytic activity. The EPR spectrum of copper in lysyl
      oxidase is typical of the tetragonally distorted, octahedrally coordinated Cu(II)
      sites observed in other amine oxidases and indicates coordination by at least
      three nitrogen ligands. The single copper atom in the lysyl oxidase monomer is
      thus essential at least for the catalytic and possibly for the structural
      integrity of this protein.

PMID- 1977744
TI  - Genetic basis of multidrug resistance of tumor cells.
AB  - Multidrug resistance in animal cells is defined as the simultaneous resistance to
      a variety of compounds which appear to be structurally and mechanistically
      unrelated. One type of multidrug resistance is characterized by the decreased
      accumulation of hydrophobic natural product drugs, a phenotype which is mediated
      by an ATP-dependent integral membrane multidrug transporter termed P-glycoprotein
      or P170. The gene coding for P170 is called MDR. The nucleotide-binding domain of
      P-glycoprotein shares sequence homology with a family of bacterial permease ATP
      binding components. In addition, P170 as a whole is structurally very similar to
      a number of prokaryotic and eukaryotic proteins believed to be involved in
      transport activities. This review summarizes our current knowledge of the
      molecular biology and clinical significance of MDR expression and P-glycoprotein
      transport activity, as well as some theories about the function of this protein
      in normal cells.

PMID- 1977747
TI  - Lys-65 and Glu-168 are the residues for carbodiimide-catalyzed cross-linking
      between the two heads of rigor smooth muscle heavy meromyosin.
AB  - We have previously demonstrated that the two heads of chicken gizzard heavy
      meromyosin (HMM) in a rigor complex with rabbit skeletal F-actin could be cross
      linked by the water-soluble carbodiimide 1-ethyl-3-[3
      (dimethylamino)propyl]carbodiimide. Here, we report the location of the cross
      linked sites in the amino acid sequence of the HMM heavy chain. One of the cross
      linked residues was identified as Glu-168 by sequencing the CN1.CN6 cross-linked
      peptide containing residues 1-77 (CN1) and 164-203 (CN6). This site is located
      close to the ATP-binding site of HMM. Since the other site was further into the
      amino acid sequence of CN1, another cross-linked peptide corresponding to
      residues 53-66 and 145-182 was isolated from the 1-ethyl-3-[3
      (dimethylamino)propyl]carbodiimide-treated acto-tryptic gizzard HMM digested
      further by other proteolytic enzymes. The amino acid sequence of this peptide and
      its cyanogen bromide fragment indicated that the cross-linking occurred between
      Glu-168 and Lys-65. Our results suggests that these two amino acid side chains
      are in contact with each other in the acto-gizzard HMM rigor complex and
      participate in the electrostatic interaction between the two HMM heads bound to F
      actin. Based on the head-to-head contact, we propose a three-dimensional model
      for the attachment of gizzard HMM heads to F-actin.

PMID- 1977748
TI  - The alpha-adrenoceptor mediating the tubular actions of the renal nerves in
      spontaneously hypertensive and stroke-prone spontaneously hypertensive rats.
AB  - 1. Experiments were undertaken in groups of pentobarbitone anaesthetized
      normotensive, spontaneously hypertensive or stroke-prone spontaneously
      hypertensive rats to determine the alpha-adrenoceptor subtype mediating renal
      nerve-stimulated tubular sodium readsorption at the level of the nephron. 2. In
      normotensive rats, stimulation of the renal nerves at low frequencies, which
      caused small changes in renal blood flow and glomerular filtration rate, caused
      significant reductions in urine volume, absolute sodium excretion and fractional
      sodium excretion of between 35 and 55% (P less than 0.01) respectively. The renal
      nerve-mediated antidiuresis and antinatriuresis were inhibited by the
      administration of doses of prazosin which selectively blocked alpha 1
      adrenoceptor vascular responses. The magnitude of the renal nerve-induced
      excretory responses was unaffected by the presence of idazoxan at a dose which
      selectively blocked alpha 2-adrenoceptor blood pressure and renal vasoconstrictor
      responses. 3. Renal nerve stimulation in spontaneously hypertensive rats caused
      small falls in renal blood flow and glomerular filtration rate but larger
      significant reductions in urine flow, absolute and fractional sodium excretions
      of between 40 and 50%, which were of similar magnitude to those observed in the
      normotensive rats. The renal nerve-induced reductions in urine flow, absolute and
      fractional sodium were abolished in the presence of prazosin but were unaffected
      by idazoxan. 4. In the stroke-prone spontaneously hypertensive rat, low level
      renal nerve stimulation had small effects on renal haemodynamics but reduced
      urine flow, absolute and fractional sodium excretions by similar magnitudes to
      those in the other groups of rats, by between 45 and 55%. These renal nerve
      induced reductions in water and sodium excretion were abolished by prazosin but
      not by idazoxan. 5. Together, these data show that in both normotensive rats and
      the two models of genetic hypertension, the renal nerves have important actions
      on the renal tubules to increase sodium and water reabsorption while having
      little effect on renal haemodynamics. In all these groups of rats this tubular
      action of the renal nerves was mediated by alpha 1- but not alpha 2
      adrenoceptors.

PMID- 1977750
TI  - Vascular papers presented at XIX World Congress of the International Society for
      Cardiovascular Surgery. Toronto, Canada, September 5-9, 1989. Proceedings.

PMID- 1977749
TI  - Effect of chronic pretreatment of guinea-pigs with beta-adrenoceptor agonists on
      the Na+,K(+)-pump in skeletal muscle.
AB  - 1. The Bmax values for the radioligand [3H]-ouabain in gastrocnemius muscle
      membranes from guinea-pigs pretreated with vehicle (0.9% saline, 0.1% ascorbic
      acid), isoprenaline (50 micrograms kg-1) or terbutaline (125 micrograms kg-1)
      subcutaneously three times daily for 7 days were 5.3 +/- 0.6; 3.1 +/- 0.4 (P less
      than 0.05) and 2.0 +/- 0.2 pmol mg-1 protein (P less than 0.01) (means +/-
      S.E.M.) respectively. Thus chronic pretreatment of the guinea-pigs with
      isoprenaline or terbutaline reduced the density of [3H]-ouabain binding sites by
      40 and 60% respectively. 2. The ouabain-sensitive uptake of 86Rb in intact soleus
      muscles from control and terbutaline pretreated animals were 10.8 +/- 1.2 and 9.0
      +/- mmol g-1 wet tissue 20 min-1 respectively. Pretreatment of guinea-pigs with
      terbutaline did not therefore significantly alter ouabain-sensitive uptake of
      86Rb (P greater than 0.1). 3. The results support a close relationship between
      regulation of beta-adrenoceptors and [3H]-ouabain binding sites. 4. Additional
      investigations are required to confirm further the dissociation between the
      function of the pump and the ouabain binding sites measured under the present
      experimental conditions.

PMID- 1977752
TI  - Adaptation to non-ammoniagenic medium and selective substrate feeding lead to
      enhanced yields in animal cell cultures.
AB  - Methods for the adaptation of three animal cell lines to media in which glutamine
      is replaced with either glutamate or 2-oxoglutarate are described. The cell lines
      differ in their rate of adaptation. The consequences of the adaptation of the
      McCoy cell line to a glutamate-based medium was measured in terms of: cell yield
      (increased by 17%), ammonia accumulation (reduced by 70%), glucose consumption
      (decreased by greater than 70%) and lactate accumulation (decreased by greater
      than 75%). The value of such adaptation and concomitant changes in energy
      metabolism lies in the potential for increased cell yields. Batch feeding of
      adapted cells in a microcarrier culture with a cocktail of glucose and amino
      acids resulted in increases in cell yields of 80% compared to unfed controls.

PMID- 1977751
TI  - Multiple forms of chicken alpha 3(VI) collagen chain generated by alternative
      splicing in type A repeated domains.
AB  - Type VI collagen is a structurally unique component widely distributed in
      connective tissues. Its molecular structure consists of monomers that have the
      potential to assemble intracellularly into dimers and tetramers which, once
      secreted, can form microfilaments by end-to-end association. Individual monomers
      are composed of chains of Mr = approximately 140,000 (alpha 1 and alpha 2) and
      greater than 300,000 (alpha 3). Type VI collagen molecules contain a short triple
      helix with large globular domains at both ends. These domains are made for their
      greatest part of repetitive units similar to type A repeats of von Willebrand
      Factor. The alpha 3(VI) chain, contributing most of the mass of the NH2-terminal
      globule, appeared heterogenous both at the mRNA and protein level. Several alpha
      3(VI)-specific clones that lack the sequences corresponding to repeats A8 and A6
      were isolated from a chicken aorta cDNA library. Northern blot hybridization of
      poly (A+)-enriched RNA from chicken gizzard with cDNA fragments corresponding to
      several individual type A repeats showed that A8- and A6-specific probes did not
      hybridize to the lower Mr transcripts. Clones spanning approximately 20 kb of the
      5'-end of the alpha 3(VI) gene were isolated from a chicken genomic library and
      subjected to analysis by restriction mapping, Southern blotting, and selective
      sequencing of the intron-exon boundaries. At the most 5'-end of the gene an
      additional type A repeat (A9), previously undetected in cDNA clones, was
      identified. Furthermore, it was determined that the presumed signal peptide and
      repeats A9 through A6 are encoded within individual exons. Reverse transcription
      and polymerase chain reaction of aorta RNA suggested that a mechanism of
      alternative mRNA splicing by a phenomenon of exon skipping generates alpha 3(VI)
      isoform variants that contain different numbers of type A repeats.
      Immunohistochemistry of frozen sections of chicken embryo tissues with repeat
      specific mAbs showed that an antibody directed against a conditional exon has a
      more restricted tissue distribution compared to an antibody against a
      constitutive exon.

PMID- 1977753
TI  - Ninth International Symposium on High-Performance Liquid Chromatography of
      Proteins, Peptides and Polynucleotides. Philadelphia, PA, November 6-8, 1989.
      Proceedings.

PMID- 1977754
TI  - Determination of nizatidine and two of its main metabolites in human serum using
      high-performance liquid chromatography.
AB  - A high-performance liquid chromatographic assay has been developed for the
      determination of nizatidine, a new histamine H2-receptor antagonist, and two of
      its main metabolites, N-desmethylnizatidine and nizatidine sulphoxide. Drugs were
      extracted with chloroform-2-propanol (90:10, v/v) from alkalinized samples of
      serum, using ranitidine as an internal standard. After evaporation of the
      extraction solvent, the residue was removed and analysed on a LiChrosorb Si60 5
      microns column with a mobile phase of acetonitrile-methanol-water-ammonia
      solution (1000:200:20:5, v/v). The compounds were detected at 320 nm. The lower
      detection limits were 6-18 ng/ml at a signal-to-noise ratio of 3. This method is
      simple and specific, and the single-step extraction makes it rapid. It is the
      first high-performance liquid chromatographic assay to be described for the
      determination of nizatidine metabolites.

PMID- 1977755
TI  - Susceptibility to thyroid autoimmune disease: molecular analysis of HLA-D region
      genes identifies new markers for goitrous Hashimoto's thyroiditis.
AB  - Hashimoto's thyroiditis has been shown to be associated with the HLA
      specificities DR4 and DR5. Since former association studies yielded variable
      results, we used novel molecular typing methods to assess predisposing
      immunogenetic factors. Gene analysis of the HLA-DR-DQ and tumor necrosis factor
      region was performed in a group of Hashimoto's thyroiditis patients and randomly
      chosen controls using standards and nomenclature of the 10th International
      Histocompatibility Workshop. Genomic DNA of patients and controls was analyzed
      using a cDNA probe of the DQB1 gene. The resulting restriction fragment patterns
      allowed the determination of newly defined DQw-types 1-9. We find the strongest
      relative risk conferred by DQw7 (RR = 4.7), that is observed in 36 of 64 patients
      (56%) and only 21 of 98 controls (21%) (P corr less than 0.002). Comparison of
      DNA sequence variation in the DQB1 gene, that is found predominantly in
      Hashimoto's thyroiditis patients, indicates that codons 45 and 57 are critical
      features in DQw7 which distinguish it from other DQw specificities. The adjacent
      DQA1 genes also display a significant association with Hashimoto's thyroiditis
      (DQA1*0201/*0301 heterozygotes were found in 37% of patients and 15% controls, P
      less than 0.03). No significant association could be found with polymorphisms of
      the tumor necrosis factor gene. These results provide a new basis for the concept
      of genetic susceptibility in Hashimoto's thyroiditis and will help to elucidate
      the underlying autoimmune mechanisms that lead to disease at the functional
      level.

PMID- 1977756
TI  - Increased circulating concentration of the N-terminus of the atrial natriuretic
      factor prohormone in persons with pheochromocytomas.
AB  - To investigate the possible relationship of hypertension and the N-terminus of
      the atrial natriuretic factor (ANF) prohormone which contains two peptides [i.e.
      pro ANF-(1-30) and pro-ANF-(31-67)] with blood pressure-lowering effects, we
      examined the circulating levels of the N-terminus of the ANF prohormone in three
      patients with pheochromocytomas before surgery, during an increase in their blood
      pressure with surgical manipulation of their tumors, and after surgery when their
      blood pressures returned to normal. The circulating levels of the whole N
      terminus [amino acids 1-98; pro-ANF-(1-98)] and pro-ANF-(31-67) from the
      midportion of the N-terminus of the ANF prohormone were increased 2-fold in
      patients with both extraadrenal and intraadrenal pheochromocytomas. In both the
      intraadrenal and extraadrenal patients N-terminus [pro-ANF-(1-98)] and pro-ANF
      (31-67) circulating levels increased further during surgical manipulation and
      returned to normal after surgical removal of their respective tumors. Each of
      these pheochromocytomas was found to have pro-ANF-(1-30) and -(31-67)-binding
      sites that were functional, since they could enhance the guanylate cyclase-cGMP
      system 2-fold in these pheochromocytomas. The entire 126 amino acids of the
      prohormone were present within each of the pheochromocytomas, since both the
      whole N-terminus and C-terminus (i.e. ANF) of the prohormone were present.
      Examination of the pheochromocytomas by electron microscopy revealed electron
      dense granules similar to those in the heart, which have been associated with the
      synthesis and storage of the ANF prohormone. We conclude that 1) the whole N
      terminus [pro-ANF-(1-98)] and pro-ANF-(31-67) of the ANF prohormone circulate at
      higher concentrations in persons with pheochromocytomas and return to normal with
      removal of the tumors; 2) pheochromocytomas contain specific binding sites for
      pro-ANF-(1-30) and -(31-67); 3) these binding sites are functional, since pro-ANF
      (1-30) and -(31-67) could enhance the enzyme guanylate cyclase within these
      tumors; and 4) the entire 126 amino acids of the ANF prohormone are present
      within these tumors, which have electron-dense granules associated with
      polypeptide hormone synthesis, suggesting that the ANF prohormone is being
      synthesized within the pheochromocytomas.

PMID- 1977757
TI  - Low prevalence of thyrotropin receptor antibody in primary hypothyroidism in
      Japan.
AB  - The prevalence of TSH receptor antibody (TRAb), measured by RRA assay (TSH
      binding inhibitor immunoglobulin, TBII) and biological stimulation-blocking assay
      (thyroid-stimulation blocking antibody, TSBAb), was examined in 134 consecutive
      patients with primary hypothyroidism due to autoimmune thyroiditis [83 patients
      with goitrous Hashimoto's disease (group A) and 51 with primary atrophic
      hypothyroidism (group B)]. In group A, TBII was detected in 6 patients (7%),
      TSBAb in 7 (8%), and both in 4 (5%). Similarly, in group B, TBII was detected in
      7 patients (14%), TSBAb in 7 (14%), and both in 5 (10%). TBII with TSBAb activity
      was low or moderate in group A, but strongly positive in group B. No relationship
      was apparent in either group between TBII or TSBAb activity and any clinical or
      laboratory parameter examined. Moreover, no clinical or laboratory findings
      distinguished patients with TRAb from those without. The low prevalence of TRAb
      in primary hypothyroidism suggests that intrathyroidal cell-mediated destructive
      mechanisms may be more important in the pathogenesis of hypothyroidism in
      autoimmune thyroiditis.

PMID- 1977758
TI  - Clinical, biochemical, and morphological correlates in patients bearing growth
      hormone-secreting pituitary tumors with or without constitutively active adenylyl
      cyclase.
AB  - Somatic mutations in the alpha-chain (alpha s) of the stimulatory regulatory
      protein of adenylyl cyclase (Gs) causing constitutive activation of the enzyme
      have been identified in a subset of human GH-secreting pituitary adenomas. This
      study reports on the differences between acromegalic patients bearing tumors
      without (group 1; n = 51) or with (group 2; n = 29) this alteration. No
      difference in age, sex, clinical features, duration of the disease, or cure rate
      was observed between the two groups. By contrast, group 2 patients had higher
      basal GH levels than group 1. Moreover, a significant difference in sellar
      morphology was found; group 2 patients more frequently showed sellas of normal
      size (grade I) than group 1. Hypersecretory activity of group 2 tumors was also
      apparent at electron microscopy; contrary to those of group 1, cells of group 2
      tumors were densely granulated and showed prominent rough endoplasmic reticulum
      and Golgi complex. With respect to group 1, group 2 patients were less responsive
      to GH-releasing hormone, while they were more sensitive to somatostatin- and
      dopamine-induced GH inhibition. These results suggest that patients with
      constitutively active adenylyl cyclase have hyperactive tumors; the sensitivity
      of these tumors to inhibitory agents (somatostatin and dopamine), possibly
      counteracting the expression of activating mutations, might explain the low rate
      of tumor growth.

PMID- 1977759
TI  - Clonal origin of pituitary adenomas.
AB  - As the pathogenesis of pituitary adenomas remains unclear, the tumor clonal
      composition of these common neoplasms was studied. Clonality was determined in
      female patients by analysis of restriction fragment length polymorphisms of the X
      chromosome genes hypoxanthine phosphoribosyl transferase and phosphoglycerate
      kinase in conjunction with their respective methylation patterns. Peripheral
      lymphocyte DNA was screened from 62 female patients undergoing transsphenoidal
      surgery for pituitary adenoma. Eleven patients were heterozygous for the BglI
      site on PGK, 4 for the BamHI site on HPRT, and 1 patient for both sites. Of these
      16 patients, 3 had acromegaly, 4 had Cushing's disease, 7 had hyperprolactinemia,
      and 2 were clinically nonfunctional. After surgery, morphological study,
      including immunohistochemistry and electron microscopy of the pathological
      specimens, allowed a direct comparison between clonality and tumor cell type.
      Control fresh normal pituitary tissue was found to be polyclonal. The following
      tumors were monoclonal: all 3 somatotroph adenomas, 4 of 4 lactotroph tumors, 3
      of 4 corticotroph cell adenomas, a gonadotroph adenoma, and a nonsecretory
      adenoma. A mixed plurihormonal adenoma was polyclonal, as were 2 tumors
      consisting of adenomatous lactotrophs interspersed with nontumorous
      adenohypophyseal pituitary tissue and one corticotroph adenoma mixed with normal
      pituitary tissue. Functional pituitary adenomas derived from somatotrophs,
      corticotrophs, or lactotrophs and nonsecretory tumors are monoclonal in nature,
      suggesting that somatic cell mutations precede clonal expansion of these cells
      and play a major role in pituitary tumorigenesis.

PMID- 1977760
TI  - Stimulation of growth hormone release in man by the potent D2-dopamine agonist CV
      205-502: comparison of responses to intravenous and oral administration.
AB  - It is well known that dopaminergic agents are stimulators of GH release in man,
      and although responses are sometimes unreliable, oral L-dopa and iv dopamine have
      frequently been employed in the evaluation of GH-deficient states. To assess the
      effects on GH secretion of a new potent D2-dopamine agonist, the
      octahydrobenzo(g)quinoline CV 205-502 (CV) we have investigated the GH responses
      in healthy male volunteers to four different iv doses. For this purpose 3
      separate groups of 9 subjects were studied. The respective groups were
      administered on separate occasions 10 micrograms CV and placebo (group 1), 5
      micrograms, 2.5 micrograms, and placebo (group 2), and 1 microgram and placebo
      (group 3). Each subject received drug and placebo in a double blind randomly
      assigned order, with at least 5 days between their administration. Active
      compound or placebo was infused over 30 min, and blood sampling was carried out
      for 72 h after cessation of infusion. Peak GH levels occurred between 45-60 min
      after the end of the infusion; the observed maximum GH concentrations were 19.2
      +/- 2.9 micrograms/L (10 micrograms, iv; P less than 0.001 vs. placebo), 9.61 +/-
      2.1 (5 micrograms, iv; P less than 0.001 vs. placebo), 4.7 +/- 1.7 (2.5
      micrograms, iv; P less than 0.05 vs. placebo), and 1.9 +/- 0.8 micrograms/L (1
      micrograms, iv; P = NS vs. placebo). The mean integrated GH secretion expressed
      in arbitrary units [area under the response curve (AUC)] up to 3 h postinfusion
      showed a typical dose-response relationship. Mean values were 1715 +/- 269.4 (10
      micrograms, iv; P less than 0.001 vs. placebo), 956.1 +/- 189.9 (5 micrograms,
      iv; P less than 0.001 vs. placebo), 312.8 +/- 105.8 (2.5 micrograms, iv), and
      162.8 +/- 47.5 (1 microgram, iv). In a second study with a separate group of 18
      volunteers, we compared the GH response to an oral dose of 100 micrograms CV with
      those to 5 micrograms CV given iv and placebo treatment. Peak GH values in this
      study were 20.3 +/- 5.5 micrograms/L (100 micrograms, orally; P less than 0.01
      vs. placebo) and 14.6 +/- 2.8 (5 micrograms, iv; P less than 0.001 vs. placebo).
      Maximum levels occurred 45 min after the infusion and 90 min after ingestion (60
      min relative to the end of the infusion).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1977761
TI  - Alpha 2-adrenergic agonism enhances the growth hormone (GH) response to GH
      releasing hormone through an inhibition of hypothalamic somatostatin release in
      normal men.
AB  - The purpose of this study was to investigate the precise mechanism by which
      central alpha 2-adrenergic pathways modulate GH secretion in humans. In 10 normal
      subjects we compared the pattern of clonidine-induced GH release to that elicited
      by GH-releasing hormone (GHRH) given at a time of presumably similar
      responsiveness of the somatotrope. We also evaluated the effect of stimulation by
      GHRH (either endogenous, by administration of clonidine, or exogenous) on the GH
      response to a further exogenous GHRH stimulation. In 2 experiments the
      administration of clonidine (0.150 mg, orally) at 0 or 60 min was followed by a
      GHRH [GRF-(1-29); 1 micrograms/kg, iv] challenge at 180 min. In other experiments
      subjects received on separate occasions placebo or clonidine at 0 min, followed
      by GHRH at 60 min and again at 180 min. In a further experiment the
      administration of clonidine at 0 min was followed by 2 GHRH challenges (60 and
      180 min later). The administration of clonidine 60 or 120 min, but not 180 min,
      before the GHRH bolus significantly (P less than 0.01) increased the GH responses
      to this challenge compared to those elicited by GHRH when given after placebo in
      a period of a similar somatotrope responsiveness. These, in turn, were
      significantly (P less than 0.05) higher than those elicited by clonidine alone.
      The close relationship between pre-GHRH plasma GH values and GHRH-elicited GH
      peaks, not observed for clonidine, was lost after pretreatment with this drug.
      These data indicate that clonidine was able to disrupt the intrinsic hypothalamic
      somatotroph rhythm, suggesting that alpha 2-adrenergic pathways have a major
      inhibitory effect on somatostatin release. Our data also indicate that GH
      responses to a GHRH bolus administered 120 min after a prior GHRH challenge are
      dependent on two parameters: the intrinsic hypothalamic-somatotroph rhythm at the
      time of the second GHRH bolus, and the magnitude of GH secretion elicited by the
      previous somatotroph stimulation. In summary, alpha 2-adrenergic agonism appears
      to act primarily in GH control by inhibiting the hypothalamic release of
      somatostatin, rather than by stimulating GHRH secretion.

PMID- 1977762
TI  - Detection of restriction fragment length polymorphisms in clinical isolates and
      serially passaged Pseudomonas aeruginosa strains.
AB  - An 800-base-pair HindIII-PstI fragment that flanks a hot spot for Tn7 insertion
      was isolated from the chromosome of Pseudomonas aeruginosa and cloned into pUC12.
      The fragment was used to probe XhoI digests of genomic DNA from 18 P. aeruginosa
      isolates collected from sputum samples of seven cystic fibrosis patients. Only
      two XhoI restriction fragment length polymorphisms (RFLPs), of 3.7 and 7.7
      kilobases (kb), were detected. Isolate WSU3531-1 (3.7-kb XhoI fragment) and
      WSU3860 (7.7-kb XhoI fragment), while isolated from the same patient, showed
      different RFLPs. Serial passages of isolate WSU3531-1 demonstrated that this
      strain was phenotypically stable. In contrast, colony and pigment variants were
      readily isolated at a frequency of 1% from serial passages of isolate WSU3860.
      When XhoI-digested genomic DNA from phenotypic variants of serially passaged
      WSU3860 were probed with the 800-base-pair HindIII-PstI fragment, the probe
      hybridized to a 10.4-kb XhoI fragment from three isolates. Restriction analysis
      of the genomic DNA digested with a variety of restriction enzymes showed that a
      2.7-kb insertion occurred in the same region for all three isolates. There
      appeared to be no correlation between changes in the RFLP and changes in colony
      morphology.

PMID- 1977763
TI  - Adhesive fimbriae associated with porcine enterotoxigenic Escherichia coli of the
      O141 serotype.
AB  - Enterotoxigenic Escherichia coli of the O141 serotype, isolated from piglets with
      postweaning coliform enteritis but producing none of the characterized adhesive
      fimbriae, was examined for fimbrial production by transmission electron
      microscopy. Two strains that produced numerous fimbriae were chosen for further
      characterization. The fimbriae were isolated and purified and had a subunit
      molecular weight of 17,000 by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. Using antiserum raised against this protein, we have shown it to
      be specific for the 17,000-molecular-weight band by immunoblotting and to be
      directed against the fimbriae by immunoelectron microscopy. These fimbriae were
      not produced when the bacteria were grown at 18 degrees C and did not show any
      mannose-resistant hemagglutination of the erythrocytes tested. We propose that
      these are a new type of adhesive fimbriae associated with porcine enterotoxigenic
      E. coli of the O141 serotype.

PMID- 1977764
TI  - Comparison of Western immunoblot antigens and interpretive criteria for detection
      of antibody to human T-lymphotropic virus types I and II.
AB  - Twenty human T-lymphotropic virus type I (HTLV-I) antibody-positive sera from
      Japan, Hawaii, and the Marshall Islands and 15 HTLV type II (HTLV-II) antibody
      positive sera from intravenous drug users in the United States were tested by
      immunoblotting with two recombinant HTLV-I proteins and three commercial kits to
      determine whether there were any differences in reactions between HTLV-I- and
      HTLV-II-positive sera by the Western immunoblot method and, also, to evaluate the
      ability of these reagents to detect HTLV-I- and HTLV-II-seropositive individuals
      by using the recommended Western blot interpretation. These sera were first
      extensively characterized by immunofluorescence, enzyme immunoassay,
      radioimmunoprecipitation assay, and Western blot using HTLV-I and HTLV-II viral
      lysates and an envelope (env) recombinant protein. Although both HTLV-I- and HTLV
      II antibody-positive sera reacted with the env protein gp68, reactions with the
      gp46 env antigens appeared to be specific for HTLV-I. It was found that the use
      of either p19 or p24 core bands plus an env reaction instead of only the p24 plus
      env reaction (as presently recommended) increased the number of positive
      interpretations for HTLV-I but had no effect on the number of HTLV-II-positive
      interpretations.

PMID- 1977765
TI  - Insertion element IS986 from Mycobacterium tuberculosis: a useful tool for
      diagnosis and epidemiology of tuberculosis.
AB  - IS986 of Mycobacterium tuberculosis belongs to the IS3-like family of insertion
      sequences, and it has previously been shown to be present in multiple copies in
      the chromosome of M. tuberculosis. In this study we investigated the value of a
      IS986-based DNA probe in the diagnosis and epidemiology of tuberculosis. IS986
      was found only in species belonging to the M. tuberculosis complex. Independent
      isolates of M. tuberculosis complex strains showed a very high degree of
      polymorphism of restriction fragments which contained IS986 DNA. In contrast,
      Mycobacterium bovis BCG vaccine strains as well as clinical isolates of M. bovis
      BCG contained one copy of IS986, which was present at the same location in the
      chromosome. Different M. tuberculosis isolates from a recent M. tuberculosis
      outbreak showed an identical banding pattern. We concluded that IS986 is an
      extremely suitable tool for the diagnosis and epidemiology of tuberculosis.

PMID- 1977766
TI  - Comparison of genomic DNAs of different enterococcal isolates using restriction
      endonucleases with infrequent recognition sites.
AB  - Epidemiologic evaluation of enterococci has been limited by the lack of a simple
      and effective method for comparing strains. In this study, we have compared
      chromosomal restriction endonuclease digestion patterns of 27 isolates of
      Enterococcus faecalis from three different locations by using pulsed-field
      electrophoresis of large chromosomal fragments (14 to 1,000 kilobases). All but
      two isolates generated a clear, evaluable pattern with a single lysis and
      digestion, and the remaining two were visualized when a larger quantity of
      bacteria was used. All isolates from different locations generated different
      restriction patterns, as did most isolates within a single location; there was
      also evidence of spread of strains between individuals in each location. The ease
      with which this analysis can be performed, together with the clarity and
      polymorphism seen in the patterns, suggests that this technique will be very
      useful for epidemiological evaluations of nosocomial enterococcal infections.

PMID- 1977767
TI  - Hemagglutination properties of Streptococcus suis.
AB  - A total of 49 strains (23 reference strains and 26 field isolates) of
      Streptococcus suis were tested for their ability to agglutinate erythrocytes from
      different animal species. Ten different hemagglutination patterns were
      established. Thirty-three strains (67%) did not agglutinate any of the
      erythrocytes tested; sixteen strains (33%) agglutinated erythrocytes from one or
      more animal species. Different strains belonging to the same capsular type
      presented different hemagglutination patterns. No correlation was found between
      the tissue origin and/or the virulence (evaluated in 4-week-old mice) of
      different field isolates and their hemagglutination activity. Hydrophobic surface
      properties were also evaluated. All S. suis strains studied appeared to possess a
      hydrophilic cell surface. Morphologically similar fimbriae were observed on
      hemagglutinating as well as on nonhemagglutinating strains of S. suis. This study
      provides evidence that certain strains of S. suis possess hemagglutinating
      properties which do not appear to involve hydrophobic interactions. The possible
      role of fimbriae in hemagglutination remains unclear.

PMID- 1977768
TI  - Endothelial cell expression of the intercellular adhesion molecule-1 (ICAM-1) in
      the central nervous system of guinea pigs during acute and chronic relapsing
      experimental allergic encephalomyelitis.
AB  - This study investigated the expression of intercellular adhesion molecule-1 (ICAM
      1; CD54) by cells of the central nervous system (CNS) during acute experimental
      allergic encephalomyelitis (EAE) and chronic relapsing EAE (CREAE). In the CNS of
      normal guinea pigs, only a few endothelial cells expressed detectable levels of
      ICAM-1, whereas during the active phases of the disease ICAM-1 was present on
      cells of the perivascular infiltrate and the endothelia of both lesion- and non
      lesion-associated blood vessels. In addition, cultured cerebrovascular endothelia
      maintained in 'standard' culture medium did not express ICAM-1, but they could be
      induced to express this antigen on incubation in a lymphocyte-conditioned medium.
      These findings suggest that the induction of ICAM-1 on CNS endothelia may be
      important in antigen presentation or in promoting lymphocyte extravasation across
      the blood-brain barrier in inflammatory disorders of the CNS.

PMID- 1977769
TI  - Brain microglia constitutively express beta-2 integrins.
AB  - Localization of beta-2 integrins in normal and Alzheimer disease temporal cortex
      was studied immunohistochemically. Resting microglia were found to express
      constitutively CD11a (LFA-1), CD11b (Mac-1, CR3), CD11c (P150, 95; CR4), and CD18
      (beta-2). They were also found to express constitutively leukocyte common antigen
      and the immunoglobulin receptor Fc gamma RI. The intensity of expression of each
      of these antigens was enhanced on reactive microglia in Alzheimer disease tissue.
      HLA-DR was detected on only a few microglia in control tissue, but was intensely
      expressed on large numbers of reactive microglia in Alzheimer tissue. These data
      are consistent with a leukocyte origin and a phagocytic role for microglia. They
      provide further evidence of an inflammatory response of brain tissue in Alzheimer
      disease. The microglia were found to make up 9-12% of the total glial population
      in gray matter and 7.5-9% in white matter.

PMID- 1977770
TI  - Elevated cerebrospinal fluid CD4+/CD8+ T cell ratio in myasthenia gravis.
AB  - The proportions of CD2+, CD4+ and CD8+ lymphocytes were determined with the 3
      layer indirect immunoperoxidase technique in the cerebrospinal fluid (CSF) of 31
      patients with myasthenia gravis (MG) and 21 control subjects without autoimmune
      or central nervous system (CNS) diseases. None of the MG patients were using
      immunosuppressive drugs and all were thymectomized shortly after CSF sampling.
      Analysis of the reference population showed that the percentage of CD4+
      lymphocytes and accordingly the CD4+/CD8+ T cell ratio is normally higher in CSF
      than in peripheral blood (PB). Compared to the controls, the mean percentage of
      CD4+ lymphocytes and the mean CD4+/CD8+ ratio in CSF were significantly higher in
      MG patients. In addition, the CD4+/CD8+ ratio was elevated in the CSF of 15 MG
      patients (48%) as a result of an elevation in the proportion of CD4+ and/or a
      decrease in CD8+ T cells. Among MG subjects the mean proportion of CD4+
      lymphocytes was higher in the CSF of patients with also an elevated number of
      enlarged stimulated lymphoid cells in their CSF, which implies that these
      lymphocytes are often of the CD4+ phenotype. The percentage of CD4+ T cells in
      CSF was significantly higher in MG patients with a hyperplastic thymus or a
      thymoma than in those with an involuted thymus. Neither in MG patients nor in the
      reference population could an association be observed between CSF and PB
      lymphocyte subsets. In the controls this suggests that immunologic events of the
      CNS are normally not directly reflected in PB.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1977771
TI  - Value of monoclonal anti-myeloperoxidase (MPO7) for diagnosing acute leukaemia.
AB  - The expression of myeloperoxidase (MPO) was studied in 100 cases of acute
      leukaemia (83 with acute myeloid leukaemia (AML) and 17 acute lymphoblastic
      leukaemia (ALL) by both a conventional cytochemical method and the
      immunocytochemical antiperoxidase (APAAP) technique using the monoclonal antibody
      MPO7. In each case the staining was evaluated by light microscopical examination
      (percentage of positive cells). Of the 83 cases of AML, 78 (93.9%) were positive
      for MPO7 compared with 70 (84.3%) by cytochemistry. Antibodies against the
      myeloid markers CD13 and CD33 were positive in 71 (85.5%) and 70 (84.3%) cases,
      respectively. Importantly, all cases of ALL were negative for both MPO7 and
      cytochemical MPO staining even when they were positive for CD13 and CD33. These
      results indicate that the anti-myeloperoxidase antibody MPO7 is the most
      sensitive and specific reagent for the diagnosis of AML and should therefore be
      included in routine immunophenotyping panels.

PMID- 1977772
TI  - Beta blockers induce different intrarenal effects in humans: demonstration by
      selective infusion of tertatolol and propranolol.
AB  - The effects of tertatolol and propranolol on renal circulation were studied in
      patients with normal renal function to test the hypothesis that various beta
      blockers may have different vasomotor effects within the renal vascular bed. Left
      renal blood flow was measured by the continuous thermodilution method before
      (t0), and 5 (t1), 10 (t2), 20 (t3), and 30 (t4) minutes after a selective
      infusion of tertatolol (0.25 mg, N = 4) or propranolol (2.5 mg, N = 4) into the
      left renal artery. Heart rate, cardiac output, aortic and right atrial pressures,
      and systemic vascular resistances did not significantly vary after either drug
      throughout the study. Plasma renin activity and plasma aldosterone in arterial
      and renal venous blood started to decrease at t1 after each drug. After
      propranolol, renal blood flow, renal vascular resistance and the renal
      arteriovenous oxygen difference were unchanged. Conversely, after tertatolol at
      t3, renal blood flow was increased (from 426 +/- 18 mL/min/1.73 m2 to 509 +/- 56
      mL/min/1.73 m2, P = .03), renal vascular resistance and renal arteriovenous
      oxygen difference were decreased (P less than .001), and the renal blood
      flow/cardiac output ratio was increased (P = .03). The filtration fraction did
      not vary after either drug, as attested by the unchanged polyfructosan extraction
      coefficient. This clinical study shows that selective infusion of a single low
      dose of tertatolol into the renal artery results in a delayed intrarenal
      vasodilator effect, while at the dose tested propranolol does not modify renal
      hemodynamics.

PMID- 1977773
TI  - Benzodiazepine hypnotics.

PMID- 1977774
TI  - Distribution and relative abundance of neurons in the pigeon forebrain containing
      somatostatin, neuropeptide Y, or both.
AB  - Immunohistochemical studies in several mammalian species and in red-eared turtles
      have shown that somatostatin (SS) and neuropeptide Y (NPY) co-occur in a
      substantial proportion of the telencephalic neurons containing either. To explore
      further the possibility that telencephalic neurons co-containing SS and NPY may
      be evolutionarily conserved among amniotes, we determined the distribution and co
      occurrence of SS and NPY in forebrain neurons in pigeons. Single-label
      immunohistochemical studies revealed the presence of overlapping populations of
      SS+ neurons and NPY+ neurons in most of the major subdivisions of the
      telencephalon. Double-label immunofluorescence studies revealed that in
      subdivisions of the telencephalon that are comparable to mammalian cortex (i.e.,
      those dorsal and lateral to the basal ganglia), the vast majority of NPY+ neurons
      were also SS+, whereas a major and regionally variable percentage of the SS+
      neurons were not NPY+. In contrast, within the basal telencephalon (including the
      basal ganglia and several other structures) neurons labeled only for NPY or only
      SS were more abundant than those containing both neuropeptides. Outside the
      telencephalon, the only forebrain cell group containing neurons in which SS and
      NPY were co-localized was in the lateral hypothalamus. A series of double- and
      triple-label immunohistochemical studies was undertaken to determine the extent
      of co-occurrence of SS and NPY in striatal neurons and the relationship of these
      neurons to striatal neurons containing other neuropeptides. In addition,
      immunohistochemical single- and double-label techniques were employed in
      conjunction with retrograde-labeling by fluorogold to determine the projections
      of SS+ and NPY+ striatal neurons. The results indicate that: 1) a population of
      striatal interneurons containing both SS and NPY exists in pigeons and
      constitutes approximately the same fraction of all striatal neurons as reported
      in mammals, 2) neurons containing NPY (but not SS) form a second, larger
      population of striatal interneurons, 3) neurons containing SS (but not NPY) form
      a third population of striatal interneurons that is approximately half as
      abundant as the NPY+ interneuron population, and 4) one-third of the substance P
      containing striatonigral projection neurons also contain SS. The existence in
      pigeons of a major population of neurons containing both SS and NPY throughout
      the telencephalon, the existence of a population of neurons containing only SS in
      cortex-equivalent parts of the telencephalon, and the existence of a population
      of interneurons containing only NPY in the striatum is consistent with findings
      in mammals and turtles.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1977775
TI  - The treatment of lichen nitidus with astemizole.

PMID- 1977776
TI  - Terbinafine: a new topically and systemically effective allylamine antifungal.
      Proceedings of a symposium held during the South Central Dermatologic Congress
      XXII and Southeastern Dermatologic Association. Captiva Island, Florida, January
      26, 1990.

PMID- 1977777
TI  - Proceedings of the eighth annual conference--the Robert Wood Johnson Dental
      Services Research Scholars Program. Cambridge, Massachusetts, May 29-31, 1990.

PMID- 1977778
TI  - Dynamic positron tomographic imaging with nitrogen-13 glutamate in patients with
      coronary artery disease: comparison with nitrogen-13 ammonia and fluorine-18
      fluorodeoxyglucose imaging.
AB  - This study was designed to test the usefulness of nitrogen-13 (N-13) glutamate
      imaging with positron emission tomography in defining myocardial ischemia in
      humans. Seventeen patients who had undergone coronary arteriography were studied
      with N-13 glutamate at peak supine exercise using a bicycle ergometer, as well as
      with the flow tracer N-13 ammonia at peak exercise during a second similar
      exercise test. Six of the patients also underwent imaging with N-13 glutamate at
      rest before exercise testing; in the remaining 11 patients imaging with fluorine
      18 (F-18) fluorodeoxyglucose was performed to assess glucose metabolism after the
      second exercise test. Seven patients had classic metabolism-flow mismatches
      consistent with ischemia (that is, decreased N-13 ammonia uptake in a region with
      relatively increased F-18 fluorodeoxyglucose uptake). There was no evidence of
      increased N-13 glutamate uptake in the ischemic mismatched regions in any of
      these patients. In all 17 patients, the uptake of N-13 glutamate during exercise
      paralleled the uptake of N-13 ammonia during exercise, suggesting that N-13
      glutamate behaves as a flow tracer rather than as a metabolic marker of ischemia
      in humans.

PMID- 1977779
TI  - Relation between beta-adrenergic blocker use, various correlates of left
      ventricular function and the chance of developing congestive heart failure. The
      Multicenter Diltiazem Post-Infarction Research Group.
AB  - This study examined the relations among beta-adrenergic blocker use, various
      correlates of left ventricular function and the chance of developing congestive
      heart failure in patients after myocardial infarction. The study was performed
      with the placebo group of the Multicenter Diltiazem Post-Infarction Trial.
      Ejection fraction data were available in 1,084 patients; of these, 557 were
      receiving a beta-blocker and 527 were not. In addition to ejection fraction,
      other correlates of left ventricular function included the presence or absence of
      pulmonary rales, chest X-ray film evidence of pulmonary congestion and the
      presence of an S3 gallop. Beta-blocker use was less frequent in patients with an
      ejection fraction less than 30%, rales, an S3 gallop and pulmonary congestion on
      chest X-ray film. Twenty-one percent of patients with an ejection fraction less
      than 30%, 42% of patients with rales, 28% of patients with an S3 gallop and 28%
      of patients with pulmonary congestion were receiving beta-blocker therapy. For
      every correlate of left ventricular function, the chance of developing congestive
      heart failure was greater in patients with diminished left ventricular function
      than in those without. For each level of left ventricular function, the chance of
      developing congestive heart failure requiring treatment was greater in patients
      not taking a beta-blocker.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1977780
TI  - Allergen-induced increase in nonspecific nasal reactivity is blocked by
      antihistamines without a clear-cut relationship to eosinophil influx.
AB  - Antihistaminic compounds have been suggested to possess other properties besides
      H1-receptor antagonism. To evaluate whether two different antihistamines could
      inhibit local eosinophil infiltration and allergen-induced nonspecific nasal
      hyperreactivity, 15 subjects with seasonal allergic rhinitis participated in a
      double-blind, randomized, placebo-controlled study outside the pollen season. At
      steady-state levels of either 60 mg of terfenadine, twice daily, cetirizine, 10
      mg once daily, or placebo, a nasal methacholine challenge was performed before
      and 24 hours after a nasal allergen challenge. The volume of the methacholine
      induced nasal secretions was measured. The response to allergen was determined
      with a scoring technique. Cells from the nasal mucosal surface were harvested
      with the aid of a rhinobrush. Both antihistamines induced a similar (p less than
      0.01) reduction in nasal symptoms after the allergen challenge compared with
      placebo. Both antihistamines inhibited the increased nonspecific nasal reactivity
      induced by methacholine 24 hours later (p less than 0.05). The allergen challenge
      induced an increase in surface eosinophils, which, however, appeared unaffected
      by any of the active treatments. Since histamine per se does not induce changes
      in nonspecific reactivity, we suggest that the antihistamines possess other
      properties besides being H1-receptor antagonists.

PMID- 1977782
TI  - Pharmacology of antihistamines.
AB  - Unlike the classic antihistamines, the new H1-receptor antagonists do not block
      cholinergic or central H1 receptors and thus do not produce the side effects,
      such as sedation, impaired psychomotor performance, and excessive mucosal drying,
      that are commonly associated with the older agents. Important pharmacokinetic and
      pharmacodynamic differences that exist among this class of antihistamines
      translate into varying pharmacologic effectiveness. Terfenadine, loratadine, and
      cetirizine are all rapidly absorbed in healthy and allergic volunteers (peak
      plasma levels, 2 to 5 hours); astemizole, however, has an initial distribution
      phase of 2 to 3 days. Further, astemizole has the longest time to relief of
      symptoms in this class; histamine wheal inhibition is not apparent until the
      second day of 10 mg dosing and does not peak for 9 to 12 days. In comparison,
      terfenadine's antihistaminic action peaks at 3 to 4 hours, loratadine's at 4 to 6
      hours, and cetirizine's at 4 to 10 hours. However, whereas the recommended dose
      of loratadine (10 mg) confers 50% wheal inhibition, 60 mg terfenadine produces an
      85% to 90% inhibition. In addition, loratadine and cetrizine have apparent dose
      related sedative effects.

PMID- 1977781
TI  - A double-blind, single-dose, crossover comparison of cetirizine, terfenadine,
      loratadine, astemizole, and chlorpheniramine versus placebo: suppressive effects
      on histamine-induced wheals and flares during 24 hours in normal subjects.
AB  - We objectively tested the relative antihistaminic effects of cetirizine, 10 mg;
      terfenadine, 120 mg; terfenadine, 60 mg; loratadine, 10 mg; astemizole, 10 mg;
      chlorpheniramine, 4 mg; and placebo in healthy, male volunteers, mean age 25 +/-
      4 years, and mean weight, 73 +/- 9 kg. The wheal areas and flare areas produced
      by epicutaneous tests with histamine phosphate, 1 mg/ml, before ingestion of the
      H1-receptor antagonist or placebo, and afterward, at 0.3 and 0.7 hours, then
      hourly from 1 to 12 hours and at 24 hours, were traced at 10 minutes and measured
      with an IBM-PC digitizer and stereometric software. In this experimental model,
      the H1-receptor antagonists differed significantly with regard to time of onset
      of action, amount of suppression of the histamine-induced wheal and flare, and
      duration of action. The rank order was, from most effective to least effective,
      cetirizine, 10 mg; terfenadine, 120 mg; terfenadine, 60 mg; loratadine, 10 mg;
      astemizole, 10 mg; chlorpheniramine, 4 mg; and placebo.

PMID- 1977783
TI  - The role of histamine in allergic rhinitis.
AB  - Studies using nasal provocation followed by nasal lavage have demonstrated that
      histamine plays an important role in the mediation of allergic rhinitis but not
      of rhinovirus infection. The response to antigen challenge is often biphasic.
      During the early response, increases in histamine levels appear to be associated
      with activation of mast cells. In a subset of persons who exhibit an additional
      late response, however, the rise in histamine is concomitant with an increase in
      the number of basophils. Further evidence of the role of histamine in allergic
      rhinitis has emerged from nasal provocation experiments involving pretreatment
      with a variety of drugs known to antagonize or affect release of histamine. Nasal
      provocation with histamine causes sneezing, itching, rhinorrhea, and nasal
      congestion. Most H1 antihistamines have been found to inhibit sneezing and to
      lessen the increase in vascular permeability, but they do not affect histamine
      release. The H1 antihistamine terfenadine, however, inhibits histamine release
      during the early response; effects on late response remain unknown. Prednisone
      decreases histamine levels during the late, but not the early, response. One-week
      pretreatment with topical steroids, on the other hand, affects both the early and
      the late response.

PMID- 1977784
TI  - Antihistamines in the treatment of clinical asthma.
AB  - Because the older antihistamines possessed relatively weak antihistaminic action,
      as well as sedative and anticholinergic effects, they could not be administered
      in doses high enough to confer relief to atopic patients with asthma. In
      contrast, the newer nonsedating, more potent H1-receptor antagonists appear to
      achieve effective histamine blockade in patients with asthma. Terfenadine and
      astemizole inhibit bronchoconstriction induced by inhaled allergens by 50% in the
      early asthmatic reaction. High-potency antihistamines also significantly reduce
      cough and wheeze as compared with placebo in grass pollen-sensitive asthma
      patients. Significant reductions in symptom severity and bronchodilator use were
      found with terfenadine, 120 mg twice daily, although these improvements may be
      confined to younger patients. Some of the newer antihistamines have demonstrated
      interesting effects on the late-phase allergic response. Azelastine partially
      inhibits bronchoconstriction in the allergen-induced late reaction of atopic
      persons with asthma, possibly by suppressing the release of additional
      inflammatory mediators. In the skin, cetirizine has been found to reduce
      eosinophil and neutrophil late-phase infiltration and prostaglandin D2 release.
      These interesting properties now warrant further investigation in clinical
      studies.

PMID- 1977785
TI  - The use of antihistamines in the prevention and treatment of anaphylaxis and
      anaphylactoid reactions.
AB  - The pathophysiologic effects of histamine in anaphylaxis have been shown to be
      mediated through H1 and H2 receptors, individually and in combination. H1
      receptors mediate coronary artery vasoconstriction, wheezing, cutaneous vascular
      permeability, and possibly an increase in pulse rate. H2 receptors stimulate
      ventricular and atrial inotropy, arterial chronotropy, coronary vasodilation, and
      rises in basophil cyclic adenosine 3':5' monophosphate (cyclic AMP). (Neither
      receptor mediates increases in cyclic AMP in mast cells.) H1 and H2 receptors in
      combination seem to be most potent in mediating flush, headache, increases in
      pulse pressure, and decreases in diastolic blood pressure. Clinical trials have
      been conducted to determine the efficacy of H1 and H2 antagonists in preventing
      anaphylactic reactions to plasma expanders, anesthesia-inducing agents, morphine,
      and radiocontrast material. Concurrently, retrospective observations of the
      prevention of anaphylactic reactions to chymopapain have been recorded. Despite
      some conflicting and inconclusive data, the sum of these studies indicates that
      pretreatment with a combination of H1 and H2 antagonists is more effective than
      H1 antagonists alone in preventing reactions to these agents. These results, when
      added to the available knowledge of the physiology of histamine release, support
      the preferential use of H1/H2 antagonist combinations in the prevention and
      treatment of anaphylaxis and anaphylactoid reactions.

PMID- 1977786
TI  - Normal responsiveness of superficial hand veins to alpha- and beta-adrenergic
      stimuli in allergic asthma: effects of terbutaline and prednisolone on beta
      adrenergic responsiveness.
AB  - Impaired function of the adrenergic-receptor system has been postulated to
      contribute to the pathogenesis of bronchial asthma. Using the dorsal hand-vein
      compliance technique, we compared the changes in diameter of superficial hand
      veins in response to phenylephrine, an alpha-adrenoceptor agonist, and to
      isoproterenol, a beta-adrenoceptor agonist, in 14 untreated patients with
      allergic asthma and in 16 nonatopic control subjects. There were no significant
      differences in the median effective dose of phenylephrine that produced 50% of
      maximal venoconstriction (ED50) or in the maximal response (Emax) between the two
      groups. Bronchial hyperreactivity (assessed by methacholine-challenge tests) in
      the patients with asthma was uncorrelated with the ED50 or Emax of isoproterenol.
      These results demonstrate no evidence for a generalized change in alpha- or beta
      adrenergic responsiveness on smooth muscle cells in asthma. Hand-vein
      responsiveness to isoproterenol was unchanged after treatment for 7 days with
      oral terbutaline (5 mg three times per day). Thus, unlike leukocytes, smooth
      muscle appears not readily susceptible to beta-adrenoceptor desensitization in
      vivo. Local infusions of prednisolone or dexamethasone during 2 hours and
      systemic administration of dexamethasone (24 hours) caused a significant fall in
      the Emax for isoproterenol. The mechanism of attenuation of beta-adrenoceptor
      responsiveness by corticosteroids remains to be determined.

PMID- 1977787
TI  - Increased bronchial hyperresponsiveness after inhaling salbutamol during 1 year
      is not caused by subsensitization to salbutamol.
AB  - Recently, it was suggested that long-term administration of an inhaled beta 2
      agonist might increase bronchial hyperresponsiveness (BHR) to histamine, possibly
      as a consequence of subsensitization to the inhaled beta 2-agonist. To test this
      hypothesis, we studied two groups of patients with asthma or with chronic
      obstructive pulmonary disease. An experimental group of 15 patients, inhaling 400
      micrograms of salbutamol four times daily during 1 year and subsequently 40
      micrograms of ipratropium bromide four times daily for 6 months, and a control
      group, consisting of 22 patients with the opposite treatment regimen. The BHR,
      the response in FEV1 to cumulative doses of salbutamol, and the number of beta 2
      adrenoceptors and antagonist affinity of these receptors on circulating
      lymphocytes were assessed at the start of the study and at 6-month intervals for
      1 1/2 years. The BHR increased significantly (p = 0.001) during the year
      salbutamol was inhaled and returned to about the value at the start of the study
      after inhaling ipratropium bromide for 6 months. No change occurred in the
      bronchodilating responses to cumulative doses of salbutamol, nor was any change
      observed in the number and the affinity of beta 2-adrenoceptors on lymphocytes.
      It was concluded that long-term use of salbutamol caused a small but significant
      increase in BHR. The increase in BHR was not caused by subsensitization of beta 2
      adrenoceptors to salbutamol.

PMID- 1977788
TI  - Effects of selective phosphodiesterase inhibitors on the polymorphonuclear
      leukocyte respiratory burst.
AB  - Modulation of the human polymorphonuclear leukocyte (PMN) respiratory burst by
      selective cyclic 3',5' adenosine monophosphate (cAMP) phosphodiesterase (PDE)
      inhibitors was studied with respect to PDE isozyme characteristics. Zaprinast, an
      inhibitor of a cyclic guanosine monophosphate (cGMP)-specific PDE (PDE I), at
      concentrations up to 100 mumol/L, had no significant effect on the respiratory
      burst. Milrinone and imazodan, inhibitors of cAMP-metabolizing, cGMP-sensitive
      PDE (PDE III), reduced the respiratory burst to 60% of control magnitude but only
      had significant effects when they were introduced at high (100 mumol/L)
      concentrations. In contrast, rolipram and RO 20-1724, inhibitors of a cAMP
      metabolizing, cGMP-insensitive PDE (PDE IV), had significant effects at low
      concentrations (0.1 mumol/L) and caused marked reduction of the respiratory burst
      at higher concentrations (25% of control at 10 mumol/L). The selective PDE IV
      inhibitors significantly potentiated PMN inhibition by isoproterenol.
      Diethylaminoethyl (DEAE)-Sepharose chromatography demonstrated a predominant PDE
      isozyme with high affinity and selectivity for cAMP that was insensitive to cGMP
      and was completely inhibited by rolipram, a PDE IV inhibitor. These results are
      consistent with the conclusion that the PMN respiratory burst is inhibited by an
      elevation of cAMP induced by PDE IV inhibition.

PMID- 1977789
TI  - Traction.

PMID- 1977790
TI  - Handgun injuries to the foot: treatment of low-velocity, high-energy wound types.
AB  - The authors present several cases of gunshot injury to the foot. Classification
      of wounds according to weapon type and caliber is discussed, as well as treatment
      rationale. Emphasis is placed on the need for detailed wound history and
      classification as precursors to adequate therapy. The low-velocity, high-energy
      wound type is introduced, and its variation from the current low- and high
      velocity classifications discussed.

PMID- 1977792
TI  - [XXIII National Congress of the Italian Society of Endocrinology. Porto Conte
      Alghero, May 27-30, 1990].

PMID- 1977791
TI  - Fracture of the os tibiale externum in a decathlete.
AB  - The upsurge in popularity in sports activities has produced a large number of
      lower extremity injuries. This article describes acute fracture of the os tibiale
      externum in a 28-year-old decathlete. The injury was treated conservatively, and
      excellent functional recovery was obtained. This is the second case of traumatic
      fracture of this accessory bone of the foot described in the English literature.
      When dealing with the feet of an athlete, supernumerary bones must be taken into
      consideration as a possible cause of serious discomfort.

PMID- 1977793
TI  - 2nd European Congress of Endocrinology. Ljubljana, Yugoslavia, July 1-6, 1990.
      Abstracts.

PMID- 1977794
TI  - Is trimethoprim-sulfamethoxazole helpful in Crohn's disease?

PMID- 1977795
TI  - Healthcare in crisis. Reducing the risk of HIV and other bloodborne diseases in
      the healthcare setting. Presentations from a roundtable discussion at the 16th
      annual conference and international meeting of the Association for Practitioners
      in Infection Control (APIC). Reno, Nevada, May 21-26, 1989. Proceedings.

PMID- 1977796
TI  - Medical congress in Africa.

PMID- 1977797
TI  - Six actin gene subfamilies map to five chromosomes of Petunia hybrida.
AB  - The Mitchell variety of Petunia hybrida possesses a superfamily of actin genes
      which contains between 100 and 200 members that can be divided into at least six
      highly divergent subfamilies. The segregation of restriction fragment length
      polymorphisms among 96 plants from two backcrosses between the Violet 23 and Red
      51 Petunia varieties and the Violet 23 x Red 51 hybrid was examined using gene
      specific probes from six Petunia actin gene subfamilies. These data were compared
      with the genotypes of each plant at 11 marker loci which are distributed among
      the seven chromosomes of Petunia and which determine flower, pollen, and isozyme
      phenotypes. From these analyses, members of these six actin gene subfamilies were
      mapped to five locations on five Petunia chromosomes: the PAc9, PAc1, PAc4, and
      PAc2 subfamilies are on chromosomes I, II, III, and VII respectively; the PAc3
      and PAc7 subfamilies are tightly linked on chromosome IV. All members of the PAc4
      subfamily cosegregated as a cluster of genes. These data are discussed regarding
      gene amplification in plants.

PMID- 1977798
TI  - Unusual T cell populations in adult murine bone marrow. Prevalence of CD3+CD4-CD8
      and alpha beta TCR+NK1.1+ cells.
AB  - The T cell populations present in normal murine bone marrow have not been
      previously analyzed in detail, mainly because of their relative rarity. In order
      to permit such analyses, bone marrow T cells were enriched by depleting Mac1
      positive cells, which constitute 65 to 90% of bone marrow cells (BMC), and then
      studied by two-color flow cytometry. Analysis of the remaining cells revealed
      that the T cell profile of adult murine bone marrow is markedly different from
      that of other lymphoid organs. A very high proportion of bone marrow CD3+ cells
      (approximately one-third) are CD4-CD8-. CD3+CD4-CD8- cells are much more
      concentrated among BMC T cells than among thymocytes or splenic T cells,
      suggesting that bone marrow may be either a site of extrathymic TCR gene
      rearrangement, or a major site to which such cells home from the thymus. The
      expression of NK1.1 was also evaluated on Mac1-depleted BMC populations.
      Surprisingly, up to 39% of alpha beta TCR+ BMC were found to express NK1.1. Most
      alpha beta TCR+NK1.1+ BMC also expressed CD4 or CD8. NK1.1+ alpha beta TCR+ cells
      represented a much greater proportion of BMC T cells than of other lymphoid
      (splenocyte or thymocyte) T cell populations. Mac1-depleted BMC of nude mice
      contained very few cells with this phenotype. These results are consistent with
      the hypothesis that NK1.1+ alpha beta TCR+ cells are generated primarily in the
      thymus of normal animals and migrate preferentially to bone marrow, where they
      may function as regulatory elements in hematopoiesis.

PMID- 1977799
TI  - Granulocyte-macrophage colony-stimulating factor increases synthesis and
      expression of CR1 and CR3 by human peripheral blood neutrophils.
AB  - Polymorphonuclear leukocytes (PMN) constitutively synthesize various plasma
      membrane proteins including CR1(3) (CD35), CR3 (or Mac-1) alpha-chain (CD11b) and
      MHC class I. PMN are also able to up-regulate rapidly the expression of CR1 and
      CR3 to the plasma membrane in response to agonists such as FMLP. To determine
      whether constitutive PMN translation was static or up-regulatable, PMN were
      cultured in the presence or absence of the cytokine granulocyte-macrophage colony
      stimulating factor (GM-CSF) for 8 h. CR1, CR3 and class I proteins
      immunoprecipitated from lysates of 35S-methionine pulse-labeled PMN were resolved
      by SDS-PAGE, fluorographed and quantified by densitometry. GM-CSF-treated PMN
      synthesized 4.5-fold more class I protein, 3.7-fold more CR1, 2.4-fold more CD11b
      and 3.4-fold more CR3 beta-chain (CD18), compared with untreated control cells.
      Actinomycin D treatment of replicate samples of PMN decreased the amount of these
      proteins synthesized by each group of PMN from 30 to 90%, implying that continued
      translation was required for the increases in protein synthesis. Nascent CR and
      class I proteins were inserted into the plasma membrane of PMN, thereby
      supplementing the molecules already expressed on the cell surface. In addition to
      these longer term effects of GM-CSF, we observed its acute up-regulatory effects
      on PMN. GM-CSF induced a five- to 12-fold increase in the expression of CR1 and
      CR3 on the PMN cell surface within 30 min. These increases were both dose- and
      time-dependent with maximum up-regulation occurring at 25 pM and at 30 min. In
      contrast to the long term biosynthetic events, this rapid up-regulation was not
      dependent on protein synthesis but was due instead to mobilization of CR from
      intracellular compartments similar to those up-regulated by FMLP. These results
      demonstrate that PMN can respond to microenvironmental stimuli such as GM-CSF
      both by rapidly up-regulating and increasing translation and expression of
      functionally important plasma membrane proteins.

PMID- 1977800
TI  - Psoriasis: the application of genetic technology and mapping.
AB  - Recent progress in molecular genetics has led to the creation of a map of the
      human genome utilizing RFLP. Given a sufficient family structure, genetic
      diseases can now be placed on this map. Genetic studies of psoriasis can both
      help resolve and be confounded by problems of disease heterogeneity,
      environmental effects on disease expression, and lack of a clear model of
      inheritance.

PMID- 1977801
TI  - Thymus-independent generation of Thy-1+ epidermal cells from a pool of Thy-1-
      bone marrow precursors.
AB  - Thy-1+ dendritic epidermal cells (Thy-1+ DEC) and immature thymocytes share
      several phenotypic features: CD45+, Thy-1+, asialo-GM1+, CD3+, CD4-, and CD8-. In
      view of this similarity, it has been suggested that the epidermis may be a site
      of either post-thymic or extra-thymic T-cell development. In order to address
      this issue, we used C3H/He/Han (Thy-1.2)----AKR/Ola (Thy-1.1) radiation bone
      marrow chimeras. Animals were first either thymectomized or sham-thymectomized,
      then lethally irradiated (750R) and, finally, reconstituted with allogeneic bone
      marrow cells previously depleted of Thy-1-bearing cells. Six weeks after bone
      marrow transplantation, spleens and lymph nodes of sham-treated animals, but not
      of thymectomized animals, contained large numbers of CD3+ donor-type Thy-1+
      cells. The epidermis of both thymectomized and sham-treated animals contained not
      only many recipient-type CD3+, Thy-1+ DEC, but also small numbers of CD3-, donor
      type Thy-1+ cells. After 4 months, the frequency of donor cells had greatly
      increased, but they still lacked CD3 antigens. Most of the donor cells had a
      rounded shape, but some exhibited a dendritic configuration. These results
      demonstrate that Thy-1- bone marrow-derived precursors of Thy-1+ DEC can migrate
      to the epidermis without thymic influence and yet acquire Thy-1 antigens during
      their journey. Although donor-type Thy-1+ epidermal cells failed to mature into
      CD3+ dendritic epidermal cells, the experimental model used in this study may be
      a versatile tool for studying the influence of thymic and extrathymic epithelia
      on T-cell maturation.

PMID- 1977802
TI  - Human nidogen gene: identification of multiple RFLP and exclusion as candidate
      gene in a family with epidermolysis bullosa (EBS2) with evidence for linkage to
      chromosome 1.
AB  - Epidermolysis bullosa (EB) is a group of heritable blistering diseases affecting
      the dermal-epidermal basement membrane zone. We have recently provided evidence
      for genetic linkage of the molecular defect in a large family with dominant
      simplex, generalized (Koebner) type of EB (EBS2) to the long arm of chromosome 1.
      Because human nidogen gene has been mapped to chromosomal locus 1q43 in the human
      genome, we examined the possibility that nidogen, an integral component of all
      basement membranes, would be the candidate gene in this family of EBS2.
      Restriction fragment-length polymorphism, which was shown with several
      restriction endonucleases to be present within the nidogen gene, was utilized for
      linkage analyses. The results using an informative PvuII polymorphism as a marker
      of allelic inheritance supported exclusion of the EBS2 locus from approximately
      10 cM in either side of the nidogen locus, when Lod score of -2.0 was taken as
      the limit of exclusion. This study demonstrates the feasibility of examining
      other families with EB for possible linkage to the nidogen locus.

PMID- 1977803
TI  - Circulating human immunodeficiency virus (HIV) p24 antigen-positive lymphocytes:
      a flow cytometric measure of HIV infection.
AB  - Asymptomatic individuals seropositive for human immunodeficiency virus (HIV)
      progress in a heterogeneous fashion toward AIDS. To facilitate monitoring of
      disease progression and response to therapy, a rapid, new flow cytometric assay
      (FCA) lymphocyte p24-FCA, has been devised to quantify peripheral blood
      lymphocytes expressing cell-associated HIV-1 p24 antigen. Results from 55
      asymptomatic, HIV-1-seropositive, serum p24 antigen-negative individuals ranged
      from undetectable (less than 0.1%) to 13.6% p24+ lymphocytes (mean, 2.0%). Mean
      values for three other groups studied were 0.1% for seronegative, viral culture
      negative laboratory workers (n = 24); 4.2% for untreated patients with AIDS (n =
      16); and 0.3% for AIDS patients receiving zidovudine (n = 11). Lymphocyte p24-FCA
      values were inversely related to the number of days to positive viral cultures
      and to levels of CD4+ lymphocytes. The ratio of p24+ lymphocytes to CD4+
      lymphocytes may reflect the fraction of infected CD4+ lymphocytes. Lymphocyte p24
      FCA determination may provide a method for monitoring response to antiretroviral
      therapy regardless of serum p24 antigen status.

PMID- 1977804
TI  - Restriction endonuclease analysis of total cellular DNA of Aspergillus fumigatus
      isolates of geographically and epidemiologically diverse origin.
AB  - No typing system exists for Aspergillus fumigatus, though isolates are
      distinguishable by phenotypic characteristics. DNA was prepared by lysis of
      protoplasts, followed by deproteination, phenolchloroform extraction, and
      dialysis. DNA prepared was of uniform size and exceeded 60 kb. After digestion
      with SalI and XhoI endonucleases, DNA was electrophoresed, stained, and
      photographed. Differences in the mobilities of 10- to 50-kb bands distinguished
      isolates. Reproducibility was shown by repeated preparations and animal passage.
      By use of a proposed notation system for describing restriction fragment length
      polymorphism patterns, 31 epidemiologically characterized isolates from three
      continents revealed 24 patterns (DNA types). Three DNA types were represented by
      3 isolates each and 1 DNA type by 2 isolates; 20 types were unique. Two groups of
      3 isolates of the same DNA type were from Stanford University Hospital. One
      patient isolate from Stanford was the same DNA type as a sewage isolate from New
      Jersey. Another Stanford isolate was the same as a German isolate. These
      observations indicate widespread dispersal of some clones and restricted locales
      for others. Paired isolates from airway fluids of three patients had two DNA
      types in each. Restriction endonuclease typing shows promise for investigating
      the epidemiology and ecology of A. fumigatus.

PMID- 1977805
TI  - A retrospective analysis of sera collected by the Hemorrhagic Fever Commission
      during the Korean Conflict.
AB  - More than 600 sera from 245 patients with a clinical diagnosis of hemorrhagic
      fever were preserved by the Hemorrhagic Fever Commission during the Korean
      Conflict, 1951-1954. These sera were tested for IgM- and IgG-specific antibodies
      to Hantaan virus by enzyme immunoassay and for hantaviral antigen by immunoassay;
      one serum from each patient was tested by plaque reduction neutralization using
      both Hantaan and Seoul viruses. Only 15 patients failed to develop antihantaviral
      antibodies; most sera contained high titered IgM antibody on admission, and all
      were IgM-seropositive by day 7 after onset. Attempts to detect hantaviral antigen
      were unsuccessful. All seropositive patients had highest plaque reduction
      neutralization titers to Hantaan virus, suggesting that this virus was
      responsible for the disease seen. These results confirm that hemorrhagic fever of
      the Korean Conflict was due to Hantaan virus and demonstrate that measurement of
      specific IgM antibody is the method of choice for diagnosis of acute disease.

PMID- 1977806
TI  - A placebo-controlled clinical trial of prednisone in the treatment of early
      hemorrhagic fever.

PMID- 1977807
TI  - Activation of the complement system in human immunodeficiency virus infection:
      relevance of the classical pathway to pathogenesis and disease severity.
AB  - In vitro studies implicate classical and alternative complement pathway
      activation in the pathogenesis of human immunodeficiency virus (HIV) infection.
      To ascertain their importance in vivo, activation fragments of the classical
      (C4d), alternative (Ba), and common (C3d) pathways were measured and fragment to
      parent molecule ratios derived in 74 HIV-infected individuals and related to
      circulating immune complex (CIC) levels, Centers for Disease Control (CDC) stage,
      and beta 2-microglobulin, neopterin, and CD4-positive (CD4+) lymphocyte levels.
      All fragments and ratios were significantly higher in patients (P less than .01)
      than controls. C4 conversion indices (C4d and C4d to C4) increased linearly with
      increasing CDC stage (P less than .001), while CD4+ lymphocytes decreased
      linearly (P less than .001). C4d, C3d, C4d to C4, and C3d to C3 correlated with
      increasing CIC and beta 2-microglobulin, and C4d and C4d to C4 correlated with
      decreasing CD4+ lymphocytes (P less than .05). The relationship of classical
      complement pathway activation to disease progression and CD4+ lymphocytes
      suggests its involvement in the pathogenesis of HIV infection.

PMID- 1977808
TI  - Analysis of lymphocytes, monocytes, and neutrophils from human immunodeficiency
      virus (HIV)-infected persons for HIV DNA.
AB  - The human immunodeficiency virus (HIV) infects and depletes or alters the
      function of cells involved in immune responsiveness. While both T helper
      lymphocytes and monocyte/macrophages can be infected via cell-surface CD4 in
      vitro, previous studies showed that few blood cells express HIV RNA in vivo. This
      study used DNA amplification to determine the levels of HIV DNA in purified
      lymphocytes, monocytes, and neutrophils from HIV-infected asymptomatic
      individuals and persons with AIDS. The average numbers of HIV DNA copies in
      lymphocytes from AIDS patients and asymptomatic individuals were similar
      (approximately 100-140 copies/150,000 cells). However, when expressed on the
      basis of numbers of CD4+ T cells, AIDS patients' cells contained approximately
      2.5 times more HIV DNA. While HIV DNA was present in lymphocytes from all 27
      subjects, little or no HIV DNA was observed in monocytes or neutrophils. Only 1
      asymptomatic person contained levels of HIV DNA in monocytes (125 proviral
      copies/150,000 cells) that were comparable to levels expressed in lymphocytes
      (160/150,000). While expression of monocyte HIV DNA in this person was persistent
      over at least 8 months, it was not observed in neutrophils, suggesting that
      monocyte HIV DNA did not originate in myeloid precursors. This study shows that
      in AIDS or asymptomatic HIV infection, lymphocytes are the predominant infected
      cell found in blood.

PMID- 1977810
TI  - Quantitation of Tamm-Horsfall protein binding to uropathogenic Escherichia coli
      and lectins.
AB  - In quantitative experiments using ELISA, binding of Tamm-Horsfall protein (THP)
      to uropathogenic Escherichia coli was studied with monoclonal antibody to THP.
      Adherence to E. coli bearing type 1 fimbriae was proportional to THP
      concentration and size of the bacterial inoculum. Type 1 fimbriae-bearing E. coli
      bound 50 times more THP than did non-type 1-fimbriated or P-fimbriated strains.
      Concanavalin A and wheat germ agglutinin bound THP in a dose-dependent fashion,
      whereas pokeweed mitogen and Vicia villosa B4 isolectin did not. Addition of
      mannose and N-acetylglucosamine reduced adherence of THP to concanavalin A and
      wheat germ agglutinin by 50%-80%. Sugar inhibition studies suggested that the
      fimbrial receptor site for THP has lectin-like properties and that THP binds to
      fimbriae via its mannose side chains. This quantitative assay is useful for
      studying the interaction between THP, uroepithelial cells, and bacteria in vitro.

PMID- 1977809
TI  - Clonal diversity and virulence factors in strains of Escherichia coli of the
      classic enteropathogenic serogroup O114.
AB  - Eighty-eight Escherichia coli strains of the enteropathogenic (EPEC) group O114
      that were isolated from humans and animals in geographically different places and
      over more than 30 years were examined for virulence markers, O:H serotypes, and
      for electrophoretic types by multilocus enzyme electrophoresis. Four major
      genetically tightly related clusters of strains showed close correlation between
      electrophoretic types and other phenotypic characters. Cluster I contained 35
      EPEC class II strains of serotypes O114:H9 and O114:H- and 5 enterotoxigenic E.
      coli belonging to O114:H21 and O114:H49. Clusters II and III comprised 36
      O114:H4, O114:H32, and O114:H- strains; most were of doubtful pathogenicity
      except one Verotoxin-positive O114:H4 strain isolated from a human with diarrhea.
      Cluster IV contained 9 classic EPEC strains of serogroup O114:H2 that were
      characterized by localized adherence to HEp-2 cells and by the EPEC adherence
      factor.

PMID- 1977811
TI  - Calcitonin gene-related peptide (CGRP) and amylin and the endocrine pancreas.

PMID- 1977812
TI  - [Psychiatric and nervous disorders].
AB  - There has recently been increased occasions to treat patients complicated with
      psychiatric and nervous disorders, in accordance with the rise of interest in
      human right and the improved social acceptance of these diseases. In the past,
      most cases were reluctantly terminated because of the prejudice against diseases
      and anxiety about the teratogenicity of the drugs. In this paper, the management
      of pregnancy and delivery including neonatal period are discussed. 1) Epilepsy
      Epilepsy is one of the most common medical complications of pregnancy with about
      0.5%. Pregnancy has no obvious effect on epilepsy. Although the teratogenicity of
      the antiepileptic drugs has been repeatedly reported, anticonvulsant therapy
      should be continued during pregnancy. Because the risk of the fetal brain damage
      from hypoxia under the epileptic convulsion of the untreated patients is higher
      than that of the teratogenicity of drugs. Phenobarbital or phenytoin are commonly
      used. Trimethadione which has been used for the petit mal epilepsy should not be
      used because of the high potent of teratogenicity. The serum concentrations of
      these drugs tend to decrease in the third trimester. Therefore the frequent
      monitoring of the serum drug concentration is very important. The monitoring of
      the blood clotting factors after delivery is also very important to avoid the
      neonatal vitamin K deficiency bleeding. Vitamin K is administered if required.
      Breast feeding is not contraindicated. Withdrawal syndrome in the neonatal state
      should not be overlooked. 2) Schizophrenia Pregnancy has no effect on
      schizophrenia. The teratogenicity of chlorpromazine or haloperidol in human
      pregnancy is thought to be negative. The function of the fetal central nervous
      system is suppressed with antipsychotic drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1977813
TI  - [Physiotherapy of respiratory failure].

PMID- 1977814
TI  - [Treatment of acute crisis of chronic respiratory failure].

PMID- 1977815
TI  - [Adverse effects of drugs used in the therapy of respiratory failure].

PMID- 1977816
TI  - [Clinical application and problems of 131-I radiotherapy and surgical therapy of
      Basedow's diseases].

PMID- 1977817
TI  - [Physiopathology and therapy of transient thyroid dysfunction syndrome].

PMID- 1977818
TI  - Effects of calmodulin antagonists on radiation-induced lipid peroxidation in
      microsomes.
AB  - Rat liver microsomes were irradiated with gamma-rays at a dose rate of 1.31 Gys
      1. The extent of lipid peroxidation, measured in terms of malondialdehyde (MDA)
      formed, increased with radiation dose. The presence of calmodulin antagonists
      during irradiation decreased lipid peroxidation. The order of their protective
      efficiency was: chlorpromazine (CPZ) greater than promethazine (PMZ) greater than
      trimeprazine (TMZ). Their protective effect was diminished in the presence of
      ferrous (Fe2+) ions and was restored on addition of EDTA. However, calmodulin
      antagonists considerably inhibited radiation-induced lipid peroxidation in the
      presence of ferric (Fe3+) ions. Calmodulin antagonists also decreased the
      cytochrome P-450 content of microsomes. These results are discussed with respect
      to their applicability to radiotherapy. A possible mechanism for the inhibition
      of radiation-induced lipid peroxidation is suggested.

PMID- 1977819
TI  - The inverse dose-rate effect for oncogenic transformation by neutrons and charged
      particles: a plausible interpretation consistent with published data.
AB  - The enhancement of oncogenic transformation in the C3H10T1/2 system by
      protraction of a high-LET irradiation has been widely reported. Prima facie, the
      results are inconsistent in that some but not all experiments have shown an
      enhancement. That the reported data follow a clear pattern is shown, and a model
      whose predictions are quantitatively consistent with these trends is discussed.
      The model, developed from that originally suggested by Rossi and Kellerer (1986),
      postulates that cells are especially sensitive to radiation during some period of
      their cycle. A sensitive period of about 1 h is shown to yield predictions
      consistent with all available data. If the suggested model is realistic and
      applicable to human cells in vivo, little enhancement would be expected for high
      LET radiations such as from radon daughters or HZE cosmic rays, though an effect
      might be expected from trapped protons on astronauts in earth orbit. For fission
      neutrons a time-dependent factor of N = 2 in the formula for dose equivalent (H =
      DQN) might be appropriate for very low dose rates, if a quality factor Q = 10
      were applied. If Q was taken as 20, then a value of N = 1 would probably be
      adequate.

PMID- 1977820
TI  - Characterization of radiation-induced damage in d(TpApCpG).
AB  - The radiation chemistry of the oligomer d(TpApCpG) X-irradiated in aqueous
      solution containing glutathione was studied. Four products were isolated by HPLC
      and characterized by NMR spectroscopy. Two of the major products are isomers of a
      5-hydroxy-5,6-dihydrothymine modification of d(TpApCpG). A dihydrothymine
      modification is also formed. The other major product is a result of strand
      scission. These products are different from the major products identified
      previously in a study of d(TpApCpG) X-irradiated in oxygenated solution. The
      effect of specific radiation-induced lesions on the behaviour of d(TpApCpG) as
      substrate to a spleen phosphodiesterase-micrococcal nuclease combination of
      enzymes and to nuclease P1 was studied. These enzymes are of interest because
      they are used in postlabelling assays of DNA damage.

PMID- 1977822
TI  - Analysis of chromatid damage in G2 phase induced by heavy ions and X-rays.
AB  - The induction of chromatid aberrations was examined in Golden hamster embryo
      (GHE) cells 2 h after exposure to X-rays or heavy ions. Compared with X-rays the
      frequencies of gaps and deletions were almost one-half in the case of He ions,
      and much lower in cells irradiated with N ions. The induction of exchanges by He
      ions and N ions was also less than that by X-rays. The relative number of gaps,
      deletions and exchanges were 0.4, 0.5 and 0.4 for He ions, and 0.2, 0.2 and 0.4
      for N ions. The mitotic indices were almost the same in X-irradiated and heavy
      ion-exposed cells. Chromatid aberrations induced by heavy ions tended to persist
      longer than those induced by X-rays during successive culture passages after
      exposure. The present results suggest a difference in the quality of chromatid
      damage induced by X-rays and heavy ions.

PMID- 1977821
TI  - Time-lapse microscopy and DNA double-strand breakage of Chinese hamster cells
      under conditions promoting or preventing PLD repair after irradiation with 60Co
      gamma rays.
AB  - We have confirmed previous time-lapse microscopic observations (Suzuki 1985)
      using Chinese hamster hai and V79 cells. The proportion of non-dividing to
      dividing cells was the same under conditions of potentially lethal damage (PLD)
      repair and non-PLD repair after irradiation with 60Co gamma-rays. This finding
      suggested that the radiation-induced damage to cellular DNA was similarly
      repaired so that cells undergo a first division to the same extent under both
      sets of conditions. In fact, direct measurement of double-strand breaks (dsb) in
      DNA from the two cell lines by the neutral elution technique showed no
      differences either in the initial amount of damage or in the time-course under
      conditions promoting or preventing PLD repair. These results indicate that PLD
      repair (i.e. an increase in cell survival) cannot be simply explained by a
      difference in the repair of dsb, but it can perhaps be explained by assuming that
      DNA damage is repaired with either fewer or more errors in the presence or
      absence of PLD repair respectively.

PMID- 1977823
TI  - Effects of 5-bromo-2-deoxyuridine and 2-deoxy-D-glucose on radiation-induced
      micronuclei in mouse bone marrow.
AB  - Effects of 2-deoxy-D-glucose (2-DG) and 5-bromo-2-deoxyuridine (BrdU) on 60Co
      gamma-radiation-induced damage in normal mouse bone marrow have been
      investigated. Cytogenetic damage as measured by the frequency of cells with
      micronuclei was studied at various time intervals after irradiation. Intravenous
      administration of 2-DG (0.1 ml, 1 g/kg body weight) just before or after whole
      body irradiation (absorbed dose 2.5 Gy) significantly reduced the micronuclei
      fraction as compared with irradiated controls. Incorporation of BrdU given
      intraperitoneally in 13 injections (0.3 ml) (total dose 2 g/kg body weight) at
      intervals of 1 h increased the micronuclei frequency, but administration of 2-DG
      significantly decreased cytogenetic damage. The results have interesting
      implications for improving tumour radiotherapy.

PMID- 1977824
TI  - The combined effects of alpha-particles and X-rays on cell killing and
      micronuclei induction in lung epithelial cells.
AB  - Understanding how cellular damage produced by high-linear energy transfer (LET)
      radiation interacts with that produced by low-LET is important both in radiation
      therapy and in evaluating risk. To study such interactions, rat lung epithelial
      cells (LEC) were grown on Mylar films and exposed to both X-rays and alpha
      particles, separately or simultaneously. Cell killing, and the numbers of
      binucleated cells and micronuclei, were measured as indicators of damage. X-rays
      and alpha-particles given separately caused dose-related increases in cell cycle
      time, with alpha-particles producing greater mitotic delay than X-rays. Damage
      from alpha-particles and X-rays given simultaneously did not interact to alter
      further the cell cycle. Cell survival data following exposure to X-rays and alpha
      particles, combined or individually, were fitted by linear-quadratic models.
      Survival curves following exposure to alpha-particles only, or to 1.0 Gy alpha
      particles plus graded X-ray doses, were adequately described using only the
      linear (alpha) term of a linear-quadratic model with alpha coefficients of 0.9 +/
      0.04 and 1.03 +/- 0.18 Gy-1, respectively. Survival following exposure to X-rays
      only or to 0.06 Gy alpha-particles combined with X-rays was best fitted using
      both alpha and beta terms of the linear-quadratic model (0.12 +/- 0.03)D + (0.007
      +/- 0.002)D2 and (0.57 +/- 0.08)D + (0.3 +/- 0.02)D2, respectively. The numbers
      of micronuclei produced by exposure to alpha-particles or X-rays alone increased
      linearly with dose, with slopes of 0.48 +/- 0.07 and 0.19 +/- 0.05
      micronuclei/binucleated cell per Gy for alpha and X-rays, respectively.
      Simultaneous exposure to graded levels of X-rays and a constant alpha dose of
      either 1.0 or 0.06 Gy increased micronuclei frequency, with a slope of 0.74 +/-
      0.05 or 0.58 +/- 0.04 micronuclei/binucleated cell per Gy, respectively. These
      slopes are similar to that produced by alpha-particles alone. These studies
      demonstrated that both cell killing and the induction of micronuclei were
      increased by combined exposures compared with that predicted for separate
      exposures.

PMID- 1977825
TI  - The present state of the automated micronucleus test for lymphocytes.
AB  - This minireview presents the state of the art with respect to automated detection
      of micronuclei (MN) in binucleated lymphocytes. Emphasis is on an image analysis
      technique, based on the principles of mathematical morphology (pattern
      recognition), which combines a personal computer with an image processing board
      and a board for microscope control. The basic idea behind this procedure is that
      nuclei plus MN and cytoplasms are analysed separately and sequentially by
      capturing images from gallocyanin-stained nuclei plus MN and naphthol yellow-S
      stained cytoplasms from one microscope field by using different filters. Major
      steps in the identification of nuclei and MN are separation of nuclei and MN from
      background by determination of periphery of the nuclei and MN, and artefact
      rejection procedures. After changing the filter, a binary image is constructed
      from cytoplasms and artefacts. Finally, stored information from selected
      binucleated objects with/without MN is combined with the cytoplasm image to check
      whether selected objects belong to the same cytoplasm. The procedure described
      above allows automated detection of binucleated lymphocytes with or without MN.
      The current capacity to detect 63% of binucleated cells and 57% of the MN within
      them is quite acceptable. To avoid false positives, artefact rejection procedures
      need to be improved before the method can be used routinely.

PMID- 1977826
TI  - X-ray inactivation of Caenorhabditis elegans embryos or larvae.
AB  - The lethal effects of X-irradiation were examined in staged populations of
      Caenorhabditis elegans embryos or larvae. Radiation resistance decreased slightly
      throughout the first, proliferative phase of embryogenesis. This might be due to
      the increase in target size, since most cells in C. elegans are autonomously
      determined. Animals irradiated in the second half of embryogenesis were about 40
      fold more resistant to the lethal effects of X-rays. This is probably due to the
      absence of cell divisions during this time. The radiation resistance increased
      still more with advancing larval stages. A radiation hypersensitive mutant, rad
      1, irradiated in the first half of embryogenesis, is about 30-fold more sensitive
      than wild-type, but in the second half it is the same as wild-type.

PMID- 1977827
TI  - An in vitro clonogenic assay to assess radiation damage in rat CNS glial
      progenitor cells.
AB  - Normal glial progenitor cells can be isolated from the rat central nervous system
      (CNS) and cultured in vitro on a monolayer of type-1 astrocytes. These monolayers
      are able to support and stimulate explanted glial progenitor cells to
      proliferate. Employing these in vitro interactions of specific glial cell types,
      an in vivo-in vitro clonogenic assay has been developed. This method offers the
      possibility to study the intrinsic radiosensitivity, repair and regeneration of
      glial progenitor cells after in vitro or in vivo irradiation.

PMID- 1977829
TI  - Higher risk coefficients associated with lower average exposure rates among
      epidemiological studies of the effects of radon in miners.

PMID- 1977828
TI  - Cell death induced in a murine mastocytoma by 42-47 degrees C heating in vitro:
      evidence that the form of death changes from apoptosis to necrosis above a
      critical heat load.
AB  - The pathogenesis of heat-induced cell death is controversial. Categorizing the
      death occurring after various heat loads as either apoptosis or necrosis might
      help to elucidate this problem, since it has been shown that these two processes
      differ in their mode of initiation as well as in their morphological and
      biochemical features. Log-phase cultures of mastocytoma P-815 x 2.1 were heated
      at temperatures ranging from 42 to 47 degrees C for 30 min. After 42 degrees C
      heating a slight increase in apoptosis was observed morphologically. However,
      after heating at 43, 43.5 and 44 degrees C, there was marked enhancement of
      apoptosis, and electrophoresis of DNA showed characteristic internucleosomal
      cleavage. With heating at 45 degrees C both apoptosis and necrosis were enhanced,
      whereas at 46 and 47 degrees C only necrosis was produced. DNA extracted from the
      46 and 47 degrees C cultures showed virtually no degradation, which contrasts
      with the random DNA breakdown observed in necrosis produced by other types of
      injury; lysosomal enzymes released during heat-induced necrosis may be
      inactivated at the higher temperatures. It is suggested that apoptosis following
      heating may be triggered either by a limited increase in cytosolic calcium levels
      resulting from mild membrane changes or by DNA damage. Necrosis, on the other
      hand, is likely to be a consequence of severe membrane disruption.

PMID- 1977830
TI  - Dose and dose-rate dependence for bone sarcomas in radium-224 patients.

PMID- 1977831
TI  - Time-dose relationship and high-LET radiation.

PMID- 1977832
TI  - Effects of alpha-particle irradiation on carcinogenesis.

PMID- 1977833
TI  - The effects of protracted administration of alpha-particle-emitting radionuclides
      on mice.

PMID- 1977834
TI  - In vitro effects of high-LET radiation.

PMID- 1977835
TI  - Abstracts of the Association for Radiation Research Meeting. Oxford, UK, 4-6
      April 1990.

PMID- 1977836
TI  - Multiple receptors on human monocytes are involved in adhesion to cultured human
      endothelial cells.
AB  - Monocytes exhibit significant basal (unstimulated) adherence to human umbilical
      vein endothelium (HUVE), which is only partially inhibited by an anti-CD18
      monoclonal antibody (mAb) (60.3). We examined factors modulating the residual,
      CD18-independent monocyte binding to HUVE by pretreating monocytes with mAb 60.3
      to eliminate CD18-dependent binding. Basal adherence was reduced from 32% +/- 2%
      to 14% +/- 2% with mAb 60.3 (means +/- SE of eight experiments; P less than
      0.01). mAb 60.3-treated monocytes were incubated with tumor necrosis factor-gamma
      (TNF-alpha), interleukin-1 (IL-1), lipopolysaccharide (LPS), N-formylmethionyl
      leucyl-phenylalamine (FMLP), or phorbol myristate acetate (PMA). Only PMA
      affected CD18-independent binding. Pretreatment with PMA alone reduced adherence
      to 21% +/- 2% (mean +/- SE of eight experiments; P less than 0.01). In
      conjunction with mAb 60.3, PMA virtually eliminated monocyte adherence to HUVE
      (7% +/- 1%, mean +/- SE of eight experiments; P less than 0.01). We also examined
      CD18-independent monocyte binding to endothelial-leukocyte adhesion molecules (E
      LAMs) induced by pretreatment of HUVE with LPS. Monoclonal antibody 60.3-treated
      monocytes increased adherence from 14% +/- 2% with unstimulated HUVE to 37% +/-
      2% with LPS-stimulated HUVE (mean +/- SE of four experiments; P less than 0.01).
      Monocytes pretreated with both mAb 60.3 and PMA increased adherence from 5% +/-
      1% with the unstimulated HUVE to 18% +/- 1% with the LPS-stimulated HUVE (mean +/
      SE of four experiments; P less than 0.01). This result implies the presence of a
      CD18-independent and PMA-insensitive receptor on human monocytes for an E-LAM
      induced by LPS. In summary, we have identified two CD18-independent mechanisms of
      monocyte adherence to HUVE; a PMA-sensitive mechanism mediating basal adherence
      and a PMA-insensitive mechanism involved in binding to E-LAMs.

PMID- 1977838
TI  - Reliability of the HLA-DQ alpha PCR-based oligonucleotide typing system.

PMID- 1977839
TI  - Restriction fragment length polymorphism DNA analysis by the FBI Laboratory
      protocol using a simple, convenient hardware system.
AB  - Restriction fragment length polymorphism analysis of human deoxyribonucleic acid
      (DNA) using two probes, pYNH24 and CMM101, was performed on the BIOS Timeframe
      system following the Federal Bureau of Investigation (FBI) Laboratory protocol
      and some variations of it. Comparable results were obtained by the different
      methods used.

PMID- 1977840
TI  - Paternity testing: blood group systems and DNA analysis by variable number of
      tandem repeat markers.
AB  - Two recent paternity cases are reported. In the first case of paternity
      exclusion, deoxyribonucleic acid (DNA) restriction fragment length polymorphisms
      (RFLPs) on variable number of tandem repeat (VNTR) loci with multiple alleles
      were informative, as well as established systems of red blood antigens, red cell
      enzymes, serum proteins, and human leukocyte antigens. In the second case, in
      which both the alleged father and the first wife were deceased, the paternal
      genotype was determined by using genetic markers from the second wife and four
      children, which then were compared with the paternal alleles of the child in
      question, the plaintiff in this case. The high probability of paternity
      (0.999,998,7) made us conclude that the man probably was the actual father. The
      DNA analysis by VNTR probes appears to be quite valuable in the study of
      paternity cases.

PMID- 1977837
TI  - Role of interleukin 6 for differential responsiveness of naive and memory CD4+ T
      cells in CD2-mediated activation.
AB  - The present study was undertaken to elucidate different requirements for CD2
      mediated activation of naive (CD45RO-) and memory (CD45RO+) CD4+ T cells. A
      mitogenic combination of anti-CD2 (anti-T11(2) and anti-T11(3] mAbs could
      effectively induce the proliferation of memory CD4+ T cells even in the absence
      of monocytes. In marked contrast, naive CD4+ T cells did not disclose any
      proliferative responses to anti-CD2 mAbs, when monocytes were absent in culture.
      This differential responsiveness of naive and memory CD4+ T cells appeared to be
      related largely to a difference in IL-6-producing ability between both
      populations. IL-6 among monocyte-derived cytokines could correct unresponsiveness
      of naive CD4+ T cells to anti-CD2 stimulation. Unlike naive CD4+ T cells, memory
      CD4+ T cells produced IL-6 by themselves, with its mRNA being expressed on anti
      CD2 stimulation. Anti-IL-6R mAb significantly inhibited proliferation of memory
      CD4+ T cells seen in the anti-CD2-stimulated cultures without monocytes,
      indicating the involvement of their own production of IL-6 in CD2-mediated
      activation. The results suggest an essential role of IL-6 for triggering of CD4+
      T cells via the CD2 molecule.

PMID- 1977841
TI  - Effect of sodium depletion on active renin, inactive renin and prekallikrein in
      plasma and urinary kallikrein excretion in glomerulonephritic patients.
AB  - To investigate the enzyme involved in the activation of plasma inactive renin in
      vivo, we measured the changes in plasma active renin, inactive renin and
      prekallikrein, and the levels of urinary kallikrein excretion in 10 primary
      glomerulonephritic patients before and after a low sodium (Na; 17 mEq/day)
      constant potassium (K; 40 mEq/day) diet for 5 days. Plasma inactive renin was
      activated by trypsin. Active renin was measured by the amount of angiotensin I
      generated when sheep substrate was added to the plasma. Plasma prekallikrein was
      measured by its activity on substrate S-2302 after activation. Urinary kallikrein
      was measured by its activity on substrate S-2266. The results showed that changes
      in plasma active renin (7.7 +/- 2.9 to 23.8 +/- 9.9 ng/ml/h), and inactive renin
      (61.5 +/- 10.2 to 145.7 +/- 53.9 ng/ml/h) and urinary kallikrein excretion (6.7
      +/- 1.1 to 10.8 +/- 2.4 nkat) were significant. No significant change in plasma
      prekallikrein was observed. The correlation between plasma active renin and
      inactive renin was significant both before and after the low salt diet. The
      correlation between the ratio of active to total renin and urinary kallikrein was
      significant before the low salt diet. These results are compatible with the
      postulate that plasma inactive renin may be a renin precursor, but they do not
      support the theory that either plasma kallikrein or renal kallikrein is related
      to activation of inactive renin in vivo.

PMID- 1977842
TI  - A simulation study on renin and aldosterone secretions in primary aldosteronism.
AB  - A system dynamics modeling method was developed to predict changes in plasma
      renin activity (PRA), plasma aldosterone (PA) and electrolyte concentrations in
      response to diuretic stimulation in patients with primary aldosteronism. Its
      clinical validity was evaluated by comparing experimental and simulation results.
      In a clinical experiment, furosemide 20 mg was given by intravenous injection to
      20 patients with primary aldosteronism. PRA, PA and electrolyte concentrations
      were measured hourly for 3 hours after administration of the drug. The computer
      simulation outputs were consistent with the experimentally measured values at
      each corresponding point of time. An analysis of model predictions indicates that
      the method may predict the changes in PRA, PA and electrolyte concentrations
      after diuretic administration in accordance with a time interval.

PMID- 1977843
TI  - Ultrasonographic findings in relation to ease of aspiration and fluid
      characteristics in thyroid cyst.
AB  - Sixty-six thyroid cysts in 65 patients were studied prospectively using the
      aspiration method and ultrasonography. The major post-aspiration ultrasonographic
      change was thyroid tissue enlargement in 95% (62/65) in addition to the decreased
      size of the thyroid cysts in all. More than double increments of thyroid tissue
      could be noted in 54% (35/65) of the patients. The color of cystic fluid was
      related to the duration of the cyst and internal echogenicity (p less than 0.01
      and p less than 0.02, respectively). Acute hemorrhage usually had a dark-reddish
      fluid and an increased echogenicity. The viscosity of the cystic fluid could
      influence the success rate of aspiration (p less than 0.05). The effect of
      aspiration was not good if the thyroid cyst had thick gelatinous fluid. Because a
      cystic goiter may be associated with malignancy, aspiration biopsy should be
      performed after the fluid is drawn especially if the thyroid tissue is expanded.
      If there is no evidence of malignancy, aspiration can be tried more than once if
      the cyst reappears.

PMID- 1977844
TI  - Using a computerized method to measure 99mTc pertechnetate uptake for the
      assessment of thyroid function: a clinical validation.
AB  - This retrospective study evaluated thyroid function by the 99mTc pertechnetate
      uptake ratio, using computer software designed in our laboratory. We expected
      that this measurement could be a precise and accurate index. The following
      studies were performed on 187 patients: (1) 24-hour radioimmunoassay of serum
      thyroid hormones, including serum thyroxine, free T4, triiodothyronine,
      thyrotropin concentrations, and T3 resin uptake; (2) 99mTc pertechnetate thyroid
      imaging and uptake measurement; and (3) 24-hour 131I thyroid uptake. Based on the
      clinical findings and the results from the predescribed laboratory tests, we
      found that: (1) the mean value of the 99mTc pertechnetate thyroid uptake ratio in
      the euthyroid groups was 2.77 +/- 1.77% (mean +/- SD); (2) the correlation
      coefficient between the 99mTc pertechnetate thyroid uptakes and the 24-hour 131I
      uptakes of the euthyroid patients was 0.71; and (3) hyperthyroidism could be
      distinguished from euthyroid condition easily. By setting the upper limit of
      euthyroid 99mTc pertechnetate thyroid uptake at 6.31%, the diagnostic sensitivity
      was 92.9%, specificity 96.1%, and accuracy 95.6% in separating hyperthyroid from
      euthyroid patients. These values were similar to those determined by the 24-hour
      131I uptake measurements. Thus, thyroid function can be evaluated simultaneously
      with a routine 99mTc pertechnetate thyroid scan. Both the patient time and cost
      can be saved with this method, since the measurement takes only 25 minutes.
      Decreased radiation exposure is another advantage of this method over the
      traditional 131I uptake measurement.

PMID- 1977845
TI  - Quantitation of calcium levels in the nails of psoriasis patients by energy
      dispersive X-ray microanalysis.
AB  - Energy dispersive X-ray microanalysis was used to study the calcium levels in the
      involved and uninvolved nails of patients with psoriasis, and in the nails of
      healthy controls. A significant difference was found between the involved and
      uninvolved psoriatic nails. Calcium levels were higher in the dystrophic nails
      than in the normal nails of the same patients, patients without nail lesions, and
      healthy controls. No difference was noted in the calcium levels of normal nails
      between psoriasis patients and healthy controls. Calcium depletion from the horny
      layer may play a role in the formation of psoriatic skin lesions.

PMID- 1977846
TI  - Osteoid osteoma: clinical and investigative features.
AB  - From 1979 to 1988, 15 cases of osteoid osteoma were diagnosed and treated at our
      hospital. There were 10 males and 5 females, the average age at the time of
      diagnosis was 17.2 years (from 5 to 54 years). The clinical features were night
      pain and localized pain in most cases. There was distinct pain relief by
      salicylate in 58% of the patients with a therapeutic trial. The duration of
      symptoms before diagnosis averaged 17.9 months (from 1 month to 10 years). Most
      of the lesions were located in the lower extremities, predominantly in the femur.
      The hip was a commonly affected site in children and young adults. The X-ray
      findings in the affected area were classical of the lesion in only 47% of the
      cases, therefore, preoperative localization of the nidus was aided by either
      tomography or CT scan. Intraoperative localization by use of an image intensifier
      and by taking X-rays of the excised specimen has proven to be reliable. All cases
      underwent en bloc resection of the lesion, and all of the patients were symptom
      free immediately after the operation, except for one recurrence. A second
      operation was performed in this case 2 years later and was successful, with
      pathological confirmation. Fourteen tumors were confirmed by histopathological
      study, one case could not be confirmed by pathological examination, however the
      patient obtained complete relief of symptoms postoperatively.

PMID- 1977847
TI  - A reevaluation of 202 patients after surgical removal of intrahepatic stones:
      with special emphasis on intrahepatic biliary stricture.
AB  - Intrahepatic stones are one of the most distressing problems of biliary diseases
      in the Orient. Surgical treatment, though greatly advanced over the last ten
      years, still poses a relatively high incidence of residual and recurrent stones.
      There were 258 patients treated by surgery for intrahepatic stones over a seven
      year period at Yuan General Hospital in Taiwan. Among them, 202 patients (78.3%)
      were adequately followed up. The patients included 82 men and 120 women with a
      mean age of 40.5 years. There were 111 cases (55.0%) involving only the left
      side, 37 cases (18.3%) involving only the right side and 54 cases (26.7%)
      involving both hepatic biliary trees. Hepatic resection, either segmentectomy or
      lobectomy (37 cases, 18.3%) and extended choledocholithotomy with or without
      drainage procedures (165 cases, 81.7%) were the surgical procedures carried out
      in these patients. Treatment failure was defined by the existence of stones,
      residual or recurrent in the bile ducts. The failure rate of extended
      choledocholithotomy (32/165, 23.6%) was higher than that of hepatic resection
      (3/37, 8.1%) although the difference was not statistically significant (p =
      0.06). The addition of various drainage procedures did not appear to affect the
      outcome of extended choledocholithotomy (p = 0.23). A significant number of
      patients had intrahepatic strictures in the biliary tracts. (62 cases, 30.7%).
      The overall treatment failure rate in patients with intrahepatic biliary
      stricture was significantly higher (28/62, 45.2%, p = 0.001) than those without
      stricture (14/100, 14%). However, hepatic resection was associated with a
      significantly lower failure rate than other treatment modalities (p less than
      0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1977848
TI  - Alpha-thalassemia minor and neonatal hyperbilirubinemia.
AB  - Infants on this island are known to have higher incidences of neonatal
      hyperbilirubinemia and alpha-thalassemia minor than Caucasians. In order to
      investigate the correlation between these two conditions, we collected a total of
      110 newborns with alpha-thalassemia minor delivered at the National Taiwan
      University Hospital during the period from January 1985 through February 1988 for
      this retrospective study. The infants in the study group were ascertained to have
      the condition by the presence of Hb Bart's with a concentration from 3% to 13%,
      in the cord blood. None of them had glucose-6-phosphate dehydrogenase (G6PD)
      deficiency. For each study infant, two control infants were selected. Criteria
      for enrollment in the control group were: (1) same sex; (2) absence of G6PD
      deficiency; and (3) birth time as close as possible to that of the study infant,
      with the 1st control born before the study infant and the 2nd control after. The
      timing of bilirubin quantitation was based on clinical judgement of jaundice by
      the pediatricians and phototherapy was started as indicated. Gestational age,
      birth weight, and rates of preterm delivery, low birth weight infants and low
      Apgar scores were comparable between the study and control groups. On day 3 after
      birth, the incidence of hyperbilirubinemia (bilirubin level over 10 mg/dl) was
      significantly lower in the study group than in the control group (0.9% vs 9.5%,
      Fisher's exact probability = 0.0012). However, the difference was not significant
      later. The incidence of phototherapy was also significantly lower in the study
      group (20%) than in the control group (31%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1977849
TI  - Apical hypertrophic cardiomyopathy: clinical, echocardiographic and angiographic
      features in 3 Chinese patients.
AB  - We present 3 cases of apical hypertrophic cardiomyopathy. The presenting symptoms
      were dyspnea on exertion in 2 of 3 patients, typical anginal pain in 1 patient,
      atypical chest pain in 1 patient, and fatigue in 1 patient. One patient was
      asymptomatic with an abnormal electrocardiogram. Sustained apical impulse was
      noted in all patients, Grade 1/6 systolic murmur was audible in 2 patients.
      Electrocardiogram showed T wave inversion in the left precordial leads in all
      patients with amplitudes of 1.4, 0.8 and 2.0 mV, respectively. Isolated apical
      hypertrophy was noted in all patients. Two-dimensional echocardiogram and the
      left ventriculogram revealed a "spade-shaped" configuration of the left
      ventricular cavity at endo-diastole in only one patient. Left ventricular end
      diastolic pressures were elevated and coronary angiograms were normal in all 3
      cases. We conclude that this disease entity should be considered in patients
      whose electrocardiogram shows a large inverted T wave in the left precordial
      leads, either accompanied by symptoms such as dyspnea on exertion or chest pain,
      or even when asymptomatic. Echocardiogram is the most useful screening tool in
      the diagnosis of apical hypertrophic cardiomyopathy.

PMID- 1977850
TI  - A case of zinc deficiency during long-term total parenteral nutrition.
AB  - A 54-year-old housewife received total parenteral nutrition (TPN) because of an
      intestinal fistula and total wound breakdown after an emergency operation for
      perforation of the ileum and diffuse peritonitis. The TPN regimen reversed the
      catabolism and resolved the abdominal wound and enterocutaneous fistula. Zinc and
      copper were not supplemented because there was no licensed parenteral trace
      element solution available. At week 17 of TPN, eczematoid dermatitis appeared on
      the face, nasolabial folds and chin, and the perineal area. These changes,
      coinciding with a serum zinc level of 20 micrograms/dl, were consistent with zinc
      deficiency. Zinc supplementation was commenced giving 6 mg of elemental zinc
      intravenously daily. The response to zinc therapy was very dramatic. Not only did
      the serum zinc level increase, but the skin changes returned to normal within 7
      days. The patient gradually resumed her usual diet and TPN was discontinued after
      an approximate duration of 21 weeks. She was later discharged in good health.

PMID- 1977851
TI  - Diagnosis of cardiac metastasis by computed tomography: report of 5 cases.
AB  - Five patients with underlying malignancy were detected antemortemly to have
      cardiac metastasis by post-enhanced CT scanning. The most common presentations
      were abnormal heart sounds, electrocardiographic changes and inexplicable heart
      failure; which lead us to suspect cardiac metastasis. One patient had an
      "engorged azygous knob" on his chest x-ray film, which provided a clue to
      possible cardiac metastasis. All of these patients had tumor thrombi in their
      large tributary veins in addition to the primary tumors. Thus, we advanced the CT
      scan to the cardiac region and cardiac metastases were, therefore, diagnosed. The
      tumor thrombi in the large tributary veins seemed to be the source for
      intracardiac spreading. Cardiac angiographies were performed in 3 patients and
      confirmed the diagnosis. We conclude that post-enhanced CT scanning is useful in
      the diagnosis of cardiac metastasis and the presence of tumor thrombi in the
      large tributary vein is an early sign of cardiac involvement.

PMID- 1977852
TI  - Reduction of serum calcium by sodium sulfonated polystyrene resin.
AB  - Sodium resin has been clinically administered against hyperkalemia widely, but
      its effects of lowering the serum calcium has never been documented. In our
      study, 7 patients with chronic renal failure were chosen at random to take sodium
      resin 30 g per day for 3 days. The sodium resin not only lowered the serum
      potassium level (p less than 0.05) but also brought down the level of serum
      calcium (p less than 0.05). The reduced ability of patients with chronic renal
      failure to absorb calcium from the gastrointestinal tract is well recognized, so
      its effects of lowering calcium will be more likely to aggravate the serum
      calcium imbalance further. If sodium resin has to be used for the maintainance of
      serum potassium in patients with chronic renal failure the serum calcium should
      be monitored closely in order to lighten the osteodystrophy and secondary
      hyperparathyroidism.

PMID- 1977853
TI  - Bilateral simultaneous transaxillary sympathectomy in treatment of palmar
      hyperhidrosis: report of 60 cases.
AB  - Bilateral simultaneous transaxillary sympathectomies (BSTS) were established in
      order to achieve a one-stage transaxillary sympathectomy in the treatment of
      palmar hyperhidrosis. The features of the BSTS were the patient's supine
      operative position, parapectoral incision, and bilateral simultaneous procedures.
      BSTS were safely performed on 60 patients during a 5-year period. No serious
      complications or recurrences were encountered. The clinical results suggest that
      BSTS is the technique of choice for one-stage transaxillary sympathectomy in the
      treatment of palmar hyperhidrosis.

PMID- 1977854
TI  - [Survival of lung cancer patients of different histologic types].
AB  - The survival curves of primary lung cancers are significantly different by
      histologic type. The purpose of this study was to analyze the survival curves and
      prognostic factors of primary lung cancers according to the histologic type at
      the Tri-Service General Hospital for the years from 1983 to 1988. All records of
      new patients admitted to TSGH with primary lung malignancies were retrieved from
      the tumor registry. The survival curve was estimated by Kaplan-Meier Limit
      Estimate. The prognostic significance of 6 clinical and pathologic factors (sex,
      age, stage of disease, primary location, histologic differentiation and
      treatment) were analyzed by single variable analysis and by Cox multivariate
      regression. There were 448 male and 199 female patients with a mean age of 61.5
      years. Adenocarcinoma was the most common histologic type found in both sexes,
      37.9% in the men and 72.8% in the women. Patients in the advanced stage with
      distant metastasis comprised 52.8%. The most frequent location was the upper lobe
      (37.8%). Methods of treatment were: a) no therapy (39.7%), b) radiotherapy
      (34.7%), c) surgery with radiotherapy (8.7%), and d) other treatment (16.9%). The
      median survival of the 647 patients was 6.8 months after diagnosis. The overall
      one-year, three-year, and five-year survival rates were 26%, 10% and 5%,
      respectively. Survival curves according to the histopathologic type demonstrated
      that patients with small cell carcinoma had the lowest cumulative survival and
      patients with adenocarcinoma had a lower cumulative survival than those with
      squamous cell carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1977855
TI  - [Behcet's disease with ocular involvement in Taiwan: a joint survey of six major
      ophthalmological departments].
AB  - A total of 103 cases with ocular involvement of Behcet's disease, seen over a
      period of 19 years (1970 to 1988), were collected from the ophthalmological
      departments of 6 major medical centers in Taiwan. The yearly number of patients
      who first visited these hospitals from 1979 through 1983 was about 5 cases and
      about 14 cases from 1984 to 1988. The domiciles of the patients were most
      commonly (51.5%) in Northern Taiwan. All 103 patients were Chinese, of which 78
      (75.7%) were men and 25 (24.3%) were women; the male to female ratio was 3.1.
      Extraocular symptoms of Behcet's disease, major or minor, and their frequencies
      among these patients included; oral ulcers, 97.1%, skin lesions, 74.8%; genital
      ulcers, 61.2%; arthritis, 47.6%; gastrointestinal lesions, 14.6%; epididymitis,
      5.8%; central nervous system lesions, 2.9%; vascular lesions, 1.9%; pulmonary
      lesions, 2.9% and urinary lesions, 4.9%. Fifty-one (49.5%) patients were of the
      complete type and 52 (50.5%) of the incomplete type. The peak distribution of
      ages at the onset of the ocular lesions, was from 20 to 40 years. As for visual
      prognosis, 37.9% of the 198 diseases eyes had a visual acuity of 0.5 or better,
      9.1% between 0.5 and 0.1, 25.3% between 0.1 and 0.01 and 27.8% were 0.01 or
      worse. In 24 (12.1%) eyes, the vision was completely lost. In HLA studies, a
      significantly increased incidence of HLA-A26 (p less than 0.01) and HLA-B51 (p
      less than 0.001) was found.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1977856
TI  - The value of body surface potential maps in assessment of experimental myocardial
      infarction.
AB  - Body surface potential maps (BSPMs) and the pathology of 32 dogs with coronary
      artery ligations were analyzed to research the application of BSPMs to acute
      myocardial infarction (AMI). The group consisted of 18 dogs with left anterior
      descending coronary artery (LAD) ligations, 8 with right coronary artery (RCA)
      ligations and 6 with left circumflex coronary artery (LCX) ligations. The
      abnormal distribution of negative potential and minimal potential were observed
      in all of the dogs. In dogs with RCA ligations, the abnormal negative potential
      displayed on the right-superior, right-inferior or right portion of the anterior
      thorax. In those with LAD ligations, the abnormal potential appeared on the left
      superior, left-inferior, middle-superior or middle portion of the anterior
      thorax. In those with LCX ligations, the abnormal potential showed on the left
      superior or left-middle portion of the thorax. A good correlation was observed
      between the area of myocardial lesion and the extent of abnormal negative
      potential distribution (r = 0.82, p less than 0.001). A close correlation was
      also found between the area of myocardial lesion and the duration of abnormal
      negative potential (r = 0.61, p less than 0.05). This study suggests that BSPMs
      are useful in the assessment of AMI in terms of diagnosis, location and extent of
      myocardial infarct.

PMID- 1977857
TI  - The coronary hemodynamics and left ventricular function in patients with
      compensated hypertension.
AB  - In this study, we tried to characterize the changes in left ventricular (LV)
      function and coronary hemodynamics in patients with compensated hypertension (HT)
      who were free from coronary artery disease. The study group consisted of 10 men
      with compensated essential HT at ages 48-65 years (mean = 58). The durations of
      HT history for the various patients ranged from 5 to 14 years. Mean arterial
      pressure (MAP) was 122 +/- 2 mmHg at the time of study. The control group was
      composed of 8 men with mild mitral valve prolapse. They were studied because of
      chest pain with no demonstratable pathological conditions. Their ages ranged from
      39 to 65 years (mean = 57). The MAP for controls was 86 +/- 3 mmHg. All patients
      in both groups underwent routine cardiac catheterization, coronary arteriography,
      and measurements of the coronary sinus (CS) and great cardiac vein (GCV) blood
      flows. Left ventricular muscle mass (LVMM), coronary resistance and coronary
      reserve were also derived from the hemodynamic study. There was a significant
      difference in the LVMM index between the study patients (114.9 g/m2) and the
      control subjects (96.8 g/m2, p less than 0.001). The LV function of the patients
      in the study group was essentially normal, but the following parameters were
      significantly different from those of the control subjects: cardiac index, stroke
      volume index, and dp/dtmax. There was a good correlation between repeated
      measurements of both the CS and GCV blood flows (r = 0.97 for both).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1977858
TI  - Emergency surgery of patients with ruptured great vessels and profound shock.
AB  - From October 1986 to March 1989, a total of 7 patients who had preoperative
      profound shock underwent surgical treatment at the National Taiwan University
      Hospital for a ruptured aorta or vena cava. All 7 patients were men. Their age
      ranged from 21 to 70 years with a mean of 45 years. Emergency operations were
      performed due to a ruptured abdominal aortic aneurysm in 2, a ruptured dissecting
      thoracic aneurysm in 1, a penetrating injury which transected the intrahepatic
      vena cava in 2, and blunt chest injury which resulted in acute traumatic aortic
      transection in 2. One of these 7 patients died of acute tubular necrosis, anoxic
      encephalopathy and secondary sepsis, in spite of successful restoration of
      circulation. Two patients had postoperative complications. One had a transient
      paraparesis after an aortic cross-clamp, and the other had a transient impairment
      of the hepatic function due to the penetrating hepatic injury and the hypoxic
      hepatic damage. All 6 survivors were restored to an excellent state of health and
      had minimal post-resuscitation sequelae. We emphasize the importance of
      aggressive surgical treatment for those patients with the threat of impending
      death due to massive hemorrhage from a ruptured great vessel.

PMID- 1977859
TI  - Low oxygenation index and pulmonary artery hypertension in predicting early death
      from adult respiratory distress syndrome (ARDS).
AB  - Hemodynamic and respiratory parameters were continuously monitored in 45 septic
      shock patients, 15 of whom developed adult respiratory distress syndrome (ARDS).
      Low oxygenation index (OI = PaO2/FIO2), pulmonary artery hypertension (high mean
      pulmonary artery pressure, MPAP) and elevated pulmonary vascular resistance (PVR)
      were observed in all ARDS, as well as in non-ARDS septic patients, as a baseline.
      These same pulmonary factors were compared between those who survived and those
      who died during the first few days (early fatalities) in both the ARDS group (5
      patients) and the non-ARDS group (8 patients). The results showed that the early
      fatalities in the ARDS group had a significantly lower (p less than 0.001) OI
      than the survivors, as well as a lower MPAP (p less than 0.01). In the non-ARDS
      group, the MPAP of the early fatalities was significantly lower (p less than
      0.01) than that of survivors, but their OI was not significantly lower. PVR, when
      compared between groups (ARDS versus non-ARDS) or between subgroups within each
      group, was elevated concurrently with the elevation of MPAP. It is concluded that
      patients with septic shock and ARDS who show a severely depressed OI and a
      modestly elevated MPAP and PVR during the first few days can be predicted to have
      a poor outcome.

PMID- 1977860
TI  - Fasting intragastric total bile acid concentration in patients with
      gastroduodenal ulcer.
AB  - It has been suggested that bile reflux is an important factor in the development
      of gastric ulcers and even duodenal ulcers. In this study we measured the fasting
      total bile acid concentration (BAC) in gastric juice and used it to represent the
      bile reflux. A total of 110 subjects were collected consecutively, including 55
      panendoscopically normal subjects as controls, 34 patients with duodenal ulcers
      (DU), 15 patients with gastric ulcers (GU) and 6 patients with both gastric and
      duodenal ulcers (GDU). The results showed a wide individual variation of
      intragastric bile acid concentration (BAC) in normal subjects and nearly 95% of
      them had concentrations below 160 mumol/L. Normal subjects above 40 years of age
      had significantly lower BACs than those under 40 years. There was no sex
      influence on BACs. In the subgroup above 40 years of age, DU and GDU patients had
      significantly higher BACs than normal controls and GU patients. We conclude that:
      (1) bile reflux is a common phenomenon in normal subjects, being mostly mild; (2)
      bile reflux may become milder after 40 years of age; (3) bile reflux is not an
      important factor in the pathogenesis of gastric ulcers; and (4) duodenal ulcers
      may not enhance the duodenogastric reflux, except in patients over 40 years of
      age.

PMID- 1977861
TI  - Enhanced natural killer cell activity in patients with cervical carcinoma by
      postoperative PS-K immunotherapy.
AB  - The cell-mediated immunity in 19 patients with stage I and II cervical carcinoma
      was evaluated before and after postoperative PS-K immunotherapy. Lymphocyte
      subpopulations were enumerated using specific monoclonal antibodies (moAbs) of
      the Leu series (Leu2, Leullb, Leu15, and Leu19) and the OKT series (OKT3, and
      OKT4). A 4-hour 51Cr-release assay was used to measure natural killer (NK) cell
      activity. Serum levels of interleukin-2 (IL-2), soluble interleukin-2 receptor
      (IL-2R), and tumor necrosis factor (TNF) were also determined before and after
      postoperative PS-K immunotherapy. The results showed that the number of cells
      carrying the marker of a non-major histocompatibility complex (MHC), restricted
      cytotoxic lymphocytes in the peripheral blood and NK activity at three different
      effector/target ratios increased significantly after postoperative PS-K
      immunotherapy. It is therefore concluded that postoperative PS-K immunotherapy
      enhanced the NK activity in patients with cervical carcinoma, in which NK
      activity tended to be lower. Further clinical investigation to assess the
      effectiveness of PS-K immunotherapy in improving the overall survival is in
      progress.

PMID- 1977862
TI  - Antimotility effects of Chinese herbal medicines on human sperm.
AB  - Caesalpinia sappan extract from a study of screened Chinese herbal medicines was
      found to be a potent agent for the inactivation of human sperm in vitro. Exposure
      of sperm from healthy donors to this agent showed remarkably reduced sperm
      motility. The antimotility effect of Caesalpinia sappan is concentration
      dependent and about 2.5 mg/ml is required to reduce motility to 50% the control
      medium (EC50). This result suggests that this traditional Chinese herbal medicine
      possesses an antimotility effect on human sperm in vitro and has the potential of
      becoming in the future a new and acceptable male oral contraceptive.

PMID- 1977863
TI  - Pleural effusion as an initial clinical presentation of myxedema: report of a
      case.
AB  - Myxedema causes functional derangement of various organs. However, it is rarely
      presented by pleural effusion. A 71-year-old man who had received radiotherapy
      for his nasal malignancy and left mandibular tumor developed bilateral, massive,
      refractory pleural effusions and respiratory embarrassment with several episodes
      of apnea in spite of treatment with diuretics, antibiotics, antituberculous
      agents, adrenal corticosteroid hormone and therapeutic thoracenteses. Definitive
      diagnosis was delayed until 6 months after admission. Replacement of the thyroid
      hormone resulted in the disappearance of the pleural effusion and the dramatic
      improvement of his long-time hearing impairment. Myxedema should be considered in
      the differential diagnosis of an unexplained pleural effusion no matter whether
      it is a transudate or an exudate.

PMID- 1977864
TI  - Malignant transformation of condyloma acuminatum: report of a case.
AB  - Condyloma acuminatum is a benign warty lesion, whose malignant change is rarely
      seen. A 69-year-old woman with a large vulvar condyloma acuminatum, which she had
      had for about 14 years, underwent a vulvectomy, and a malignant component to the
      lesion was found unexpectedly. The continuity from a benign to a malignant lesion
      was evident in the histopathologic examination. Infection with human
      papillomavirus type 6 was documented by DNA hybridization. The use of a one-step
      reverse dot blot hybridization with nonisotope DNA probe in this case was
      convenient and is recommended.

PMID- 1977865
TI  - Benign cystic mesothelioma of the peritoneum: report of a case.
AB  - A 36-year-old multiparous woman presented with the chief complaint of mass and
      fullness over the lower abdomen for the previous 3 months. Abdominal ultrasound
      revealed a uniloculated, thin-walled cyst attached to the peritoneal surface of
      the right lower abdomen. The cyst was surgically excised and confirmed to be
      cystic mesothelioma of the peritoneum by histopathologic and immunohistochemical
      studies. Benign cystic mesothelioma is an extremely rare intraperitoneal tumor.
      Although its etiology remains unclear, one distinctive clinicopathologic feature
      is a symptomatic abdominal mass in young females. The presence of a thin-walled
      cyst attached to the peritoneum on ultrasound should alert physicians to the
      possibility of this disease. The treatment of choice is complete resection and
      reexcision may be required due to a preponderance for local recurrence. Regular
      postoperative ultrasound follow-up is recommended to check for possible
      recurrence.

PMID- 1977866
TI  - A new sperm collection method for treatment of retrograde ejaculation.
AB  - Retrograde ejaculation is an uncommon but treatable form of male infertility.
      Successful recovery of motile spermatozoa from a post-ejaculatory urine for
      artificial insemination is dependent on careful regulation of osmolarity and
      acidity of the bladder contents into which the ejaculate emanates, and the
      separation of the motile spermatozoa from the debris and cells which are found in
      these specimens. A pregnancy established by artificial insemination of
      spermatozoa recovered from bladder contents of a patient suffering from
      retrograde ejaculation is presented. The techniques for preparing the urinary
      bladder for spermatozoal survival and the removal of debris and cells by delicate
      centrifugation are discussed.

PMID- 1977867
TI  - Oculopalatal myoclonus: report of a case.
AB  - We report a patient who developed a delayed onset of oculopalatal myoclonus,
      characterized by synchronous oscillatory movements of the eyeballs, soft palate
      and the orbicularis oculi muscle, 5 months after a pontine hemorrhage. The
      involuntary oscillations did not affect the speech or swallowing but continued in
      sleep with decreased amplitudes. These oscillations also failed to respond to
      clonazepam therapy and the patient was unable to voluntarily suppress them for
      several minutes. A temporary association in synchronous titubation of the head
      was also observed. A characteristic vertical ocular oscillation was demonstrated
      in an oculogram. This is in accordance with the midline form of oculopalatal
      myoclonus.

PMID- 1977868
TI  - [A evaluation of chlorhexidine as an endosonic irrigan].
AB  - Chlorhexidine has been utilized as a root canal irrigant since 1971. It is a
      broad-spectrum antimicrobial agent with minimal toxicity and residual long-term
      antibacterial capability. Although a sodium hypochlorite solution has been shown
      to have a better antimicrobial effect than chlorhexidine, its corrosive effect
      has prevented its further use especially since the in vitro antimicrobial effect
      of chlorhexidine has been shown to not be much less. However, the efficacy of
      chlorhexidine as an endodontic irrigant and intracanal medicament, requires
      further research in vivo. Therefore, in this study, the clinical effects of
      chlorhexidine were evaluated by comparing its antimicrobial properties with other
      endodontic irrigants. One hundred and fifty teeth were selected and evenly
      divided into 6 groups according to their pathological status. The root cancals
      were prepared with conventional hand filing or ultrasonic filing, respectively,
      and were rinsed singly with either chlorhexidine, EDTA or distilled water. The
      contents of each root canal before or after debridement were cultured in an
      incubator. The results showed that chlorhexidine with hand filing in one week and
      with endosonics in 48 hours had a better antimicrobial effect than did EDTA. As
      compared with the control group (distilled water), chlorhexidine showed marked
      antimicrobial effect in both hand and endosonic filing. It is concluded that
      chlorhexidine has an antibacterial effect as an endodontic irrigant in clinical
      applications.

PMID- 1977869
TI  - [Nutritional care of severe acute head injury patients: formulas for early
      enteral alimentation].
AB  - The objectives of this study were: 1) to determine a suitable enteral
      alimentation formula to meet calorie and protein requirements in acute severe
      head injury; and 2) to evaluate the effect of different alimentation formulas on
      the outcomes of 60 patients, who suffered from acutely severe head injury without
      other major injuries and who were treated without steroids. These patients were
      randomly divided into three groups and enteral feeding was started within 24 hrs.
      of admission or postoperative. Among the two study groups Group I was fed a high
      protein (2.5-3.0 g/kg), high calorie (BEE x 1.2 x 1.6) diet, and Group III was
      fed a moderately high protein (2.0-2.5 g/kg), high calorie diet. The control
      group (Group II) was fed a normal protein (1-1.5 g/kg), normal calorie (30-35
      Kcal/kg) diet. There were no significant differences between the three groups in
      anthropometric measurements, visceral protein, total lymphocyte count, and
      creatinine height index. The percentage of ideal body weight change in Group III
      patients (-4.2 +/- 1.0%) was significantly different (p less than 0.01) from
      Group I (-8.1 +/- 1.0%) and Group II (-11.8 +/- 1.8%). The discharge coma scale
      and 6-month outcomes were not significantly different between the three groups.
      This study demonstrated that a moderate high protein (2.0-2.5 g/kg), high calorie
      (BEE x 1.2 x 1.6) diet offers better nutritional status. The outcome of severe
      head injury patients did not change with the different enteral nutritional
      support formulas.

PMID- 1977870
TI  - [An in vitro study of lithium index in healthy Chinese].
AB  - The lithium index, a ratio of erythrocyte (intracellular) to plasma
      (extracellular) lithium concentrations, were studied by in vitro method in 22
      healthy volunteers, 15 men and 17 women. Their mean age was 31.0 +/- 4.6 years
      (ranging from 26 to 41 years). In the study design, 20 ml of venous blood was
      taken from each subject into a test tube containing sodium citrate at the room
      temperature and erythrocytes were separated from plasma immediately. Then, the
      whole procedures for preparation and determination of lithium index were
      performed by using Pandey's method. Lithium levels were measured by atomic
      absorption spectrophotometry. Values of lithium index in vitro thus obtained
      were: 0.43 +/- 0.13 (range, 0.23-0.73) in men plus women; 0.37 +/- 0.10 (range,
      0.23-0.57) in men; 0.49 +/- 0.13 (range, 0.26-0.73) in women. Women had a
      significantly higher Li+ index in vitro than men (t = 2.86, d.f. = 30, p less
      than 0.005). The possible reasons for the difference of the Li+ index in vitro
      between our result and other studies were discussed.

PMID- 1977871
TI  - Production of a non-functional nef protein in human immunodeficiency virus type 1
      infected CEM cells.
AB  - The nef gene product of the human immunodeficiency virus (HIV) is suggested to be
      a negative factor involved in down-regulating viral expression by a mechanism in
      which the correct conformation of the nef protein is essential. The nef protein
      expressed by vaccinia virus recombinants is phosphorylated by protein kinase C.
      We investigated the synthesis of the nef protein and its state of phosphorylation
      during HIV-1 infection of a T4 cell line (CEM cells). Maximum synthesis of viral
      proteins occurred 3 days after infection, when more than 90% of cells were
      producing viral proteins. The synthesis of the nef protein was detected in
      parallel with the env and gag proteins. As expected, the nef protein was
      myristylated but not phosphorylated, and its half-life was less than 1 h. By the
      use of the polymerase chain reaction technique, we isolated and sequenced the nef
      gene of this HIV-1 stock. Two significant mutations were observed. Firstly,
      threonine, at amino acid number 15, the site of phosphorylation by protein kinase
      C, was mutated into an alanine, and secondly aspartic acid of the tetrapeptide
      WRFD, which is probably involved in GTP binding, was mutated into an asparagine.
      The mutated nef gene was expressed in a vaccinia virus system, in which it was
      not phosphorylated and its half-life was dramatically reduced compared to the
      wild-type nef gene product. Furthermore, down-regulation of CD4 cell surface
      expression was no longer affected by the mutated nef gene. These results
      emphasize that phosphorylation of the nef protein provides an efficient test to
      monitor its biological activity.

PMID- 1977873
TI  - A survey of neuroleptic malignant syndrome.

PMID- 1977872
TI  - Articulatory impairment associated with tardive dyskinesia.
AB  - The speech of two patients with tardive dyskinesia was studied, and one
      neuroleptic-treated patient having no signs of overt tardive dyskinesia served as
      control. A structured interview, including reading, repetition of sentences, and
      spontaneous conversation, was performed. A phonetic transcription and analysis of
      abnormal phonemes was done by a linguist under blind conditions. Both patients
      with tardive dyskinesia had abnormal phonemes whereas the control patient had
      none. These differences could not be explained by age, direct neuroleptic effect,
      or neuroleptic exposure time. The abnormal phonemes were all consonants. The
      authors conclude that tardive dyskinesia may cause articulatory communication
      problems.

PMID- 1977874
TI  - Major depression with psychosis: demographic, phenomenological, and outcome
      characteristics in one hospitalized population.

PMID- 1977875
TI  - Aedes furcifer and other mosquitoes as vectors of chikungunya virus at Mica,
      northeastern Transvaal, South Africa.
AB  - From 1977 to 1981, studies were conducted on a farm at Mica where Aedes furcifer
      had been a vector during an epidemic of chikungunya virus in 1976 to determine
      whether the virus persisted in this mosquito, the likelihood of vertical
      transmission, and whether any other Aedes species could have been vectors. Aedes
      furcifer/cordellieri was the only prevalent tree hole Aedes which fed readily on
      monkeys and humans and occurred through the summer until the onset of winter.
      Virus was not isolated from 7,241 females and 4,052 males of this group, which
      were largely Ae. furcifer and which included a sample of the first post-epidemic
      population. Five additional Aedes species were prevalent in bamboo pots, 3 of
      which (Ae. aegypti, Ae. fulgens and Ae. vittatus) were shown to be competent
      laboratory vectors. Virus was not isolated from a sample of 13,029 such newly
      emerged mosquitoes representing the first post-epidemic population. It is
      concluded that Ae. furcifer is an epidemic-epizootic vector which does not
      maintain the virus at Mica and that no other mosquito species could have been
      important vectors.

PMID- 1977876
TI  - Evaluation of hand applied naled thermal fog for Wyeomyia control.
AB  - Tests on the effect of hand applied naled thermal fog, both as a single treatment
      on one day/week and a single treatment on 3 successive days, did not control
      Wyeomyia vanduzeei and Wy. mitchellii. Five-min landing/biting counts in a native
      oak/palm woodland demonstrated that single applications produced an average
      landing rate decrease of 13%. Treatments 3 days in succession did not suppress
      the landing rate.

PMID- 1977877
TI  - The relationship between size and parity status of field collected Culiseta
      melanura.
AB  - The relationship between body size and parity status of adult female Culiseta
      melanura collected from 3 locations in northeastern United States was studied by
      measuring wing lengths and examining ovaries of individual mosquitoes. Virus
      isolation was attempted from Cs. melanura collected in Maryland and in New
      Jersey. At all 3 locations, the size of Cs. melanura collected varied from large
      in the spring, to small in the summer. In New Jersey and Maryland mosquitoes
      collected in the fall were again large. The size of Massachusetts mosquitoes
      collected in the summer versus the fall was not different. In general, parous
      mosquitoes were larger than nulliparous mosquitoes in the spring but smaller than
      nulliparous ones in the fall. Eastern equine encephalomyelitis (EEE) and
      Highlands J (HJ) viruses were recovered from Cs. melanura only during the late
      summer when mosquitoes were small or during the fall months when larger
      mosquitoes were collected. We conclude that there is no detectable association
      between Cs. melanura size and parity status and that there is no obvious effect
      of mosquito size on EEE or HJ virus transmission.

PMID- 1977878
TI  - A new mutant, White larva, of the mosquito Toxorhynchites splendens: genetics and
      cannibalism.
AB  - A strain of a new body-color mutant, white larva (wl), was established from a
      field-collected wild-type strain of Toxorhynchites splendens. The mutant can be
      distinguished from the wild type in both the larval and pupal stages, but not in
      the adult. Crossing experiments confirmed its mode of inheritance to be a single
      recessive system. This is the first visible mutant found in Tx. splendens. Larvae
      of the wl phenotype seem to be recognized as prey by other individuals in mass
      larvae rearing.

PMID- 1977879
TI  - Distribution and abundance of larval Coquillettidia perturbans in a Florida
      freshwater marsh.
AB  - All instars of larval Coquillettidia perturbans were found in the same habitats,
      but early instar larvae were more aggregated than later instars. Larvae were most
      numerous in areas dominated by arrow-arum (Peltandra virginica) and maidencane
      (Panicum hemitomon), less so in areas dominated by sedges (Carex spp.) and
      miscellaneous mixed vegetation, and least abundant in pickerelweed (Pontederia
      cordata) areas. Larvae were uncommon in open water or in areas dominated by small
      floating plants such as water fern (Salvinia rotundifolia), duckweekd (Lemna
      minor) and mosquito fern (Azolla caroliniana). Larval concentrations were
      greatest in water 35-70 cm deep. There was also a tendency for them to
      concentrate in areas beyond 25 m from shore. Larvae were log-normally distributed
      in favorable sites and became progressively more aggregated as sites became less
      favorable.

PMID- 1977881
TI  - Portable mosquito net support devices for indoor and outdoor use.
AB  - Polyvinyl chloride plumbing and electrical cover pipes are used in the assembly
      of low priced devices that will support mosquito bed nets. One such device is a
      frame assembled from components in a lightweight compact set with dimensions of
      75 x 20 x 5 cm, weighing approximately 0.5 kg. It can be mounted on a wall or
      attached to a stand of adjustable height which is also made from plumbing pipes.
      This support frame provides minimum obstruction of view and movement as it is
      attached at only one point. It can be used indoors or outdoors either for
      sleeping on beds or on the ground. A second device is composed of short pipe
      sheaths attached to bed legs for easy insertion or removal of support poles.

PMID- 1977880
TI  - Hexane preserves biological activity of isozymes and DNA.
AB  - Live or frozen insects are required for using isozyme and DNA RFLP methods in
      studies on population structure, systematics and incrimination of sibling
      species. Difficulty in keeping insects alive or unavailability of liquid nitrogen
      or dry ice at regular intervals during extended collection trips poses a serious
      problem. We describe a method for preserving insects in hexane, under field
      conditions, for isozyme and DNA analysis.

PMID- 1977882
TI  - Literature references for mosquitoes and mosquito-borne diseases.

PMID- 1977883
TI  - Rat brain synaptosomes prepared by phase partition.
AB  - Synaptosomes from rat forebrain can easily be isolated by combining
      centrifugation with partition in an aqueous two-phase system composed of dextran
      T500 and polyethylene glycol 4000 in which synaptosomes have an extreme affinity
      for the upper phase. The fraction thus obtained has been characterized by
      electron microscopy and biochemical markers for synaptosomes and some other cell
      components. The contamination by microsomes, free mitochondria, and myelin was
      4.4, 3.2, and 0.1%, respectively. The morphometric analysis of the electron
      micrographs shows that greater than 60% of the structures are synaptosomes. This
      preparation of the isolation procedure is remarkably short (less than 1 h),
      formance as assayed by their respiratory activities and ATP level in the absence
      and presence of depolarizing agents. Synaptosomes prepared by phase partition
      release the neurotransmitter glutamate in a Ca2(+)-dependent manner. The duration
      of the isolation procedure is remarkably short (less than 1 h), no
      ultracentrifuge is required, and the method can be applied for small- or large
      scale preparations.

PMID- 1977884
TI  - Presynaptic glutamate/quisqualate receptors: effects on synaptosomal free calcium
      concentrations.
AB  - Intracellular free [Ca2+]i was measured using fura-2 in synaptosomes prepared
      from cerebral cortices of adult male rats (12 weeks). L-(+)-Glutamate, D-(-)
      glutamate, and quisqualate produced similar dose-dependent increases in [Ca2+]i,
      with EC50 values of 0.38 microM, 0.74 microM, and 0.1 microM, respectively, and
      maximum increases of approximately 40%. Ibotenate showed less affinity (EC50 4.4
      microM) but had a greater maximum effect (57%). N-methyl-D-aspartate (NMDA) and
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) did not increase
      [Ca2+]i. The increases in [Ca2+]i induced by quisqualate and ibotenate were not
      diminished in the absence of extrasynaptosomal Ca2+. L-2-Amino-4
      phosphonobutyrate (L-AP4) (1 microM) completely blocked the changes in [Ca2+]i
      induced by L-(+)-glutamate, D-(-)-glutamate, quisqualate, or ibotenate. The
      effects of quisqualate and ibotenate on [Ca2+]i were also blocked by coincubation
      of synaptosomes with L-(+)-serine-O-phosphate (L-SP) (1 mM) (which, like L-AP4,
      blocks the effects of quisqualate and ibotenate on inositol phospholipid
      metabolism). 6-Cyano-7-nitroquinoxaline-2,3-dione (CNQX) had no effect on agonist
      mediated increases in [Ca2+]i when coincubated with either quisqualate or
      ibotenate. These data are consistent with the existence of presynaptic glutamate
      receptors (of the excitatory amino acid metabotropic type) which activate
      phospholipase C leading to the elevation of inositol 1,4,5-trisphosphate and
      release of Ca2+ from intracellular stores.

PMID- 1977885
TI  - Antinociceptive actions of alpha 2-adrenoceptor agonists in the rat spinal cord:
      evidence for antinociceptive alpha 2-adrenoceptor subtypes and dissociation of
      antinociceptive alpha 2-adrenoceptors from cyclic AMP.
AB  - The antinociceptive actions of intrathecal injections of two alpha 2-adrenergic
      agonists, UK-14,304 and guanfacine, were investigated in rats after pretreatment
      of the animals with the noradrenaline neurotoxin N-2-chloroethyl-N-ethyl-2
      bromobenzylamine (DSP4) 14 days in advance. The chronic noradrenaline depletion
      induced by DSP4 caused a marked increase in sensitivity of the antinociceptive
      action of UK-14,304 in the tail-flick test. By contrast, the antinociceptive
      effect of guanfacine was not appreciably affected by the DSP4 treatment. The
      antinociceptive effects of both UK-14,304 and guanfacine were blocked by
      intraperitoneal injections of yohimbine, a result indicating that both drugs
      induced their actions by activating alpha 2-adrenoceptors. Both UK-14,304 and
      guanfacine were found to reduce the production of cyclic AMP (cAMP) in the spinal
      cord, as determined using an in vitro radioisotopic method. The cAMP inhibitory
      effects of both agonists were effectively blocked by yohimbine, but not by
      prazosin, a finding indicating the alpha 2-adrenergic nature of the response.
      However, the cAMP inhibitory effect of UK-14,304 was not potentiated by
      pretreatment with DSP4, a finding in marked contrast with the strong potentiation
      of the antinociceptive action of UK-14,304 induced by the chronic depletion of
      endogenous noradrenaline. Moreover, intrathecal injections of forskolin, which
      increased the endogenous levels of spinal cord cAMP fivefold, did not modify the
      antinociceptive effects of UK-14,304 or guanfacine in neither normal nor DSP4
      treated animals. It is suggested that there exist pharmacologically differing
      alpha 2-adrenergic receptor pathways capable of mediating antinociceptive effects
      at the level of the spinal cord. The cAMP inhibitory actions of spinal cord alpha
      2-adrenoceptors appear not to be directly linked with the antinociceptive actions
      of these receptors.

PMID- 1977886
TI  - The glycine antagonist 7-chlorokynurenic acid blocks the effects of N-methyl-D
      aspartate on agonist-stimulated phosphoinositide hydrolysis in guinea-pig brain
      slices.
AB  - Despite having no effect on basal phosphoinositide hydrolysis. N-methyl-D
      aspartate (NMDA) inhibited carbachol-stimulated accumulation of 3H-inositol
      phosphates and enhanced that due to noradrenaline in guinea-pig cerebral cortex
      slices. The glycine antagonist 7-chlorokynurenic acid inhibited the effects of
      NMDA and this inhibition was reversed by glycine. The action of 7-chlorokynurenic
      acid was not mimicked by strychnine or HA 966 (1-hydroxy-3-aminopyrrolid-2-one).
      L-Glutamate also inhibited carbachol-stimulated accumulation of 3H-inositol
      phosphates, but this inhibition was not blocked by 7-chlorokynurenic acid. The
      data are consistent with glycine maintaining tonic control over NMDA receptor
      activity in guinea-pig brain.

PMID- 1977887
TI  - Alpha-latrotoxin releases both vesicular and cytoplasmic glutamate from isolated
      nerve terminals.
AB  - alpha-Latrotoxin causes a massive release of endogenous glutamate from guinea-pig
      cerebrocortical synaptosomes. There appear to be two components to the release.
      In the first 2 min following addition of 1.3 nM alpha-latrotoxin, glutamate
      release is largely energy dependent. Superimposed upon this release is a more
      slowly developing but ultimately much more extensive release of cytoplasmic
      glutamate together with gamma-aminobutyric acid and nonvesicular amino acids such
      as aspartate and alpha-aminoisobutyrate. In parallel with this cytoplasmic
      release there is an extensive depletion of ATP, a massive rise in cytoplasmic
      free Ca2+ concentration, and a severe restriction of synaptosomal respiratory
      capacity. The cytoplasmic release is only partially Na+ dependent, eliminating a
      simple reversal of the plasma membrane acidic amino acid carrier. It is concluded
      that alpha-latrotoxin releases both transmitter and cytoplasmic pools of amino
      acids in synaptosomes and causes a major disruption of terminal integrity.

PMID- 1977888
TI  - Comparison of the in vitro receptor binding properties of N-[3H]methylspiperone
      and [3H]raclopride to rat and human brain membranes.
AB  - The aim of the present investigation was to study and compare the in vitro
      binding properties of the two radioligands N-[3H]methylspiperone ([3H]NMSP) and
      [3H]raclopride. These compounds, labeled with 11C, have been extensively used in
      positron emission tomography studies on central dopamine D2 receptors in
      schizophrenic patients, although with diverging results. One study (using
      [11C]NMSP) showed an increased dopamine receptor density in drug-naive
      schizophrenic patients, whereas in another study (using [11C]raclopride) the
      density in schizophrenic patients was no different from that in healthy controls.
      In the present study, using in vitro binding techniques, the density of the
      binding sites was found to be similar irrespective of which of the two
      radioligands was used (20 fmol/mg wet weight in rat striatum and 10 fmol/mg in
      human putamen; the 5-hydroxytryptamine 2 receptors were blocked with 40 nM
      ketanserin). [3H]NMSP had a 10-fold higher affinity (KD, 0.3 nM in rat striatum
      and 0.2 nM in human putamen) than [3H]raclopride (KD, 2.1 nM in rat striatum and
      3.9 nM in human putamen), which was consistent with the longer dissociation half
      life of [3H]NMSP compared with [3H]raclopride (14.8 and 1.19 min, respectively).
      There was an approximate overall similarity between the inhibition constants for
      five dopamine antagonists, chlorpromazine, haloperidol, raclopride, remoxipride,
      and NMSP, when using either radioligand. The Ki values were, however, two- to
      four-fold higher when using [3H]NMSP as the radioligand, irrespective of
      inhibiting compound, except for chlorpromazine (and haloperidol in human
      putamen). NMSP was found to inhibit the binding of [3H]raclopride competitively,
      whereas raclopride inhibited the binding of [3H]NMSP both competitively and
      noncompetitively. This difference suggests that part of the binding site is
      exclusively used by NMSP and can only be allosterically interfered with by
      raclopride. It is proposed that [3H]NMSP binds to an additional set of accessory
      binding sites, presumably located more distantly from the agonist binding active
      site than the sites to which [3H]raclopride binds.

PMID- 1977889
TI  - Uptake of glutamate and cysteine in C-6 glioma cells and in cultured astrocytes.
AB  - The uptake of glutamate in rat glioma C-6 cells and cultured astrocytes derived
      from rat cerebral hemispheres was found to be mediated by a Na(+)-dependent and a
      Na(+)-independent system. The Na(+)-dependent system was inhibited by aspartate
      and was consistent with the commonly occurring system designated system X-AG. The
      Na(+)-independent system was inhibited by cystine and was consistent with system
      x-c described in various types of cells in the periphery. It was also found that
      quisqualate selectively and competitively interfered with the Na(+)-independent
      glutamate uptake. In C-6 cells, the glutamate uptake via systems X-AG and x-c
      accounted for approximately 35% and 55% of the total uptake, respectively, at
      0.05 mM glutamate. In cultured astrocytes, the glutamate uptake via system X-AG
      was very potent, whereas the uptake via system xc- was relatively weak and its
      contribution to the total uptake of glutamate seemed almost negligible. However,
      in both C-6 cells and astrocytes, system xc- was necessary for the uptake of
      cystine, another substrate of system xc-. Cystine in the culture medium was an
      essential precursor of glutathione, and the inhibition of the cystine uptake by
      excess glutamate as a competitor led to a severe deficiency in glutathione,
      followed by cell degeneration.

PMID- 1977890
TI  - Homologous desensitization of the D1 dopamine receptor.
AB  - Preincubation of D384 cells, derived from the human astrocytoma cell line G-CCM,
      with dopamine resulted in a time-dependent attenuation of cyclic AMP
      responsiveness to subsequent dopamine stimulation. This effect was agonist
      specific because the prostaglandin E1 (PGE1) stimulation of cyclic AMP of
      similarly treated cells remained unchanged. The attenuation by dopamine was
      concentration dependent with a maximum observed at 100 microM. A comparison of
      dopamine concentration-response curves of control and dopamine-preincubated cells
      revealed no change in the Ka apparent value, but a marked attenuation of the
      maximal response. Preincubation of cells with dopamine in the presence of D1 but
      not D2 selective antagonists partially prevented the observed attenuation.
      Attenuations in dopamine responsiveness were also obtained when D384 cells were
      preincubated with D1 but not D2 receptor agonists. The level of attenuation
      attained related to agonist efficiency in stimulating cyclic AMP: SKF38393 less
      than 3,4-dihydroxynomifensine less than fenoldopam less than 2-amino-6,7
      dihydroxy-1,2,3,4-tetrahydronaphthalene = dopamine. However, increasing the
      efficiency of 3,4-dihydroxynomifensine stimulation of cyclic AMP, using the
      synergistic effect of adding a low concentration of forskolin, produced no
      further change in the attenuation of the subsequent response to dopamine. Thus,
      the D1 dopamine receptors expressed by D384 cells undergo homologous
      desensitization. Uncoupling of the D1 dopamine receptor appears to be independent
      of cyclic AMP formation, analogous to a mechanism proposed for the beta
      adrenergic receptor.

PMID- 1977891
TI  - Species and regional differences in the expression of cell-type specific elements
      at the human and rat tyrosine hydroxylase gene loci.
AB  - The expression of the catecholamine biosynthetic enzyme, tyrosine hydroxylase
      (TH), is confined to several different types of neuroendocrine cells. Using a
      transient assay system, we examined more than 10 kb of the human TH gene and 6.5
      kb of 5' flanking sequences of the rat TH gene for DNA elements that confer cell
      type specific expression. Surprisingly, these elements do not appear to be
      conserved in position or sequence across species. When plasmids containing DNA
      sequences - 749 bp from the transcription start site of the rat gene were
      introduced into PC12 cells, up to sixfold higher levels of expression were
      observed as compared to the same fragments introduced into HepG2 cells or LAN-1
      cells. In contrast to the rat gene, analogous fragments of the human 5' promoter
      failed to confer cell-type specific expression. However, when plasmids containing
      a truncated thymidine kinase promoter and either orientation of a 760 by 3' human
      TH gene fragment were introduced into PC12 and LAN-1 cells, we observed a six-
      and 3.5-fold increase, respectively, over that observed for HepG2 cells.
      Subsequent deletion of this fragment led to significant activation of
      transcription in PC12 and HepG2 cell lines. These data indicate the presence of
      multiple elements contributing to the cell-type specific expression of tyrosine
      hydroxylase genes.

PMID- 1977892
TI  - Neuronal plasticity and astrocytic reaction in Down syndrome and Alzheimer
      disease.
AB  - Proteins relatively enriched in neurons (neural cell adhesion molecule (NCAM) and
      D3-protein) or in glia (glutamine synthetase, glial fibrillary acidic protein
      (GFAP) and S100) were measured by quantitative immunochemical methods in autopsy
      samples of the cerebral cortex of subjects with Alzheimer disease (AD) and adults
      with Down syndrome (DS), the latter also presenting manifest signs of Alzheimer
      type of neuropathology. The trend of changes was similar in AD and DS, but more
      marked in the latter. The biochemical make-up of astrocytes was differentially
      affected: in both the frontal and DS temporal cortex the specific concentration
      of glutamine synthetase was unaltered, while that of S100 and the soluble form of
      GFAP was markedly elevated (about 260% and 690% of control values, respectively).
      In the AD frontal cortex the estimates for glutamine synthetase were normal,
      while S100 and GFAP were about 180% and 230% of control. The observations (normal
      GS and elevated levels of the other markers) might suggest that the pathological
      changes involve a differentiated astrocytic reaction and that the astrocytic
      reaction is more marked in DS than in AD. In DS the increase in S100 could be
      explained, in part, by a gene dosage effect and in part by reactive gliosis. The
      neuronal markers were also differentially affected. In comparison with
      appropriate controls, the concentration of D3-protein in frontal cortex was
      decreased by 24% in DS and by 14% in AD, whereas NCAM levels were not
      significantly affected. The ratio of NCAM to D3-protein was significantly
      increased by 32% and 8.5% in DS and AD, respectively. These observations are
      consistent with the view that the destruction of mature neuronal structures (as
      marked by the D-3 protein) coincides with the formation of new neuronal membranes
      (as indicated by NCAM), i.e. in these degenerative disorders plastic changes are
      taking place involving cerebral cortex neurons in which trophic substances may be
      instrumental.

PMID- 1977893
TI  - Role of EPSPs in initiation of spontaneous synchronized burst firing in rat
      hippocampal neurons bathed in high potassium.
AB  - 1. Spontaneous discharges that resemble interictal spikes arise in area CA3 b/c
      of rat hippocampal slices bathed in 8.5 mM [K+]o. Excitatory postsynaptic
      potentials (EPSPs) also appear at irregular intervals in these cells. The role of
      local synaptic excitation in burst initiation was examined with intracellular and
      extracellular recordings from CA3 pyramidal neurons. 2. Most (70%) EPSPs were
      small (less than 2 mV in amplitude), suggesting that they were the product of
      quantal release or were evoked by a single presynaptic action potential in
      another cell. It is unlikely that most EPSPs were evoked by a presynaptic burst
      of action potentials. Indeed, intrinsic burst firing was not prominent in CA3 b/c
      pyramidal cells perfused in 8.5 mM [K+]o. 3. The likelihood of occurrence and the
      amplitude of EPSPs were higher in the 50-ms interval just before the onset of
      each burst than during a similar interval 250 ms before the burst. This likely
      reflects increased firing probability of CA3 neurons as they emerge from the
      afterhyperpolarization (AHP) and conductance shunt associated with the previous
      burst. 4. Perfusion with 2 microM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a
      potent quisqualate receptor antagonist, decreased the frequency of EPSPs in CA3
      b/c neurons from 3.6 +/- 0.9 to 0.9 +/- 0.3 (SE) Hz. Likewise, CNQX reversibly
      reduced the amplitude of evoked EPSPs in CA3 b/c cells. 5. Spontaneous burst
      firing in 8.5 mM [K+]o was abolished in 11 of 31 slices perfused with 2 microM
      CNQX.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1977894
TI  - APV-sensitive dorsal root afferent transmission to neonate rat sympathetic
      preganglionic neurons in vitro.
AB  - 1. Intracellular recordings were made from antidromically identified sympathetic
      preganglionic neurons (SPNs) in transverse thoracolumbar spinal cord slices from
      neonate (12- to 22-day-old) rats. 2. Electrical stimulation of dorsal roots or
      dorsal root entry zone elicited in SPNs an excitatory postsynaptic potential
      (EPSP) or multiple EPSPs of varying latencies. The EPSP could be graded by
      varying the stimulus intensity and, on reaching the threshold, discharged an
      action potential. 3. The dorsal root-evoked EPSPs had a mean synaptic latency of
      2.6 ms (range: 1.2-11 ms), suggesting a polysynaptic pathway. The EPSPs were
      characteristically slow in onset with a mean rise time and half-decay time of 8.3
      and 23 ms, respectively. 4. At the resting membrane potential of -50 to -60 mV,
      the amplitude of EPSPs recorded in normal (1.3 mM Mg2+) Krebs solution was
      reduced by membrane hyperpolarization or depolarization. In Mg2(+)-free solution,
      EPSPs were potentiated and reached threshold for spike discharge. 5. The EPSPs
      were suppressed by the nonselective glutamate receptor antagonist kynurenic acid
      (0.1-0.5 mM) and by the N-methyl-D-aspartate (NMDA) receptor antagonists D-2
      amino-5-phosphonovaleric acid (APV; 1-10 microM) and ketamine (5-10 microM), but
      not by the quisqualate (QA)/kainate (KA) receptor antagonist 6,7
      dinitroquinoxaline-2,3-dione (DNQX, 1-10 microM). The latter depressed the EPSPs
      elicited by stimulation of lateral funiculus in the same SPNs. 6. NMDA applied by
      pressure elicited a depolarization in the SPNs. In normal Krebs solution the
      response was voltage dependent with the peak amplitude occurring around -60 mV;
      conditioning depolarization or hyperpolarization diminished the
      response.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1977895
TI  - Membrane properties and response to opioids of identified dopamine neurons in the
      guinea pig hypothalamus.
AB  - The electrophysiological properties and opioid responsiveness of the dopamine
      containing neurons in the arcuate nucleus of the guinea pig hypothalamus were
      examined. Dopamine-containing neurons, identified immunocytochemically by the
      presence of tyrosine hydroxylase, had a mean length-to-width profile of 14.9 +/-
      4.4 x 11.5 +/- 3.1 microns (N = 14). The Na+ action potential of these neurons
      was of short duration, and induction of repetitive firing (20-50 Hz) caused an
      afterhyperpolarization of 6-9 mV in amplitude, with a decay half-time of
      approximately 1.5 sec. Dopamine-containing cells exhibited a low threshold spike,
      which induced 1-4 Na+ action potentials. This potential had a threshold close to 
      65 mV, could not be induced without prior hyperpolarization and was not sensitive
      to TTX. Dopamine-containing neurons also exhibited a time- and voltage-dependent
      inward current at potentials negative to -70 mV, and Cs+ blocked this
      conductance. The mu-opioid agonist Tyr-D-Ala-Gly-mePhe-Gly-ol hyperpolarized (14
      +/- 3 mV) dopamine neurons via induction of an outward current (93 +/- 44 pA near
      the resting membrane potential) which had a reversal potential similar to that
      expected for a selective potassium conductance. TTX (1 microM) did not block the
      opioid effects. These results show that dopamine neurons of the arcuate nucleus
      differ in their intrinsic conductances and their responsiveness to opioids from
      other CNS dopaminergic neurons. Furthermore, opioid activation of a potassium
      conductance resulted in a direct hyperpolarization of dopamine neurons of the
      arcuate nucleus, and we suggest that this mechanism may underlie the effects of
      opioids on dopamine-mediated prolactin release.

PMID- 1977897
TI  - Frontiers in disease prevention. A National Conference on the Impact of the U.S.
      Preventive Services Task Force Guidelines. 5-6 June, 1989.

PMID- 1977896
TI  - Massive increases in extracellular potassium and the indiscriminate release of
      glutamate following concussive brain injury.
AB  - An increase in extracellular K+ concentration ([K+]c) of the rat hippocampus
      following fluid-percussion concussive brain injury was demonstrated with
      microdialysis. The role of neuronal discharge was examined with in situ
      administration of 0.1 mM tetrodotoxin, a potent depressant of neuronal
      discharges, and of 0.5 to 20 mM cobalt, a blocker of Ca++ channels. While a small
      short-lasting [K+]c increase (1.40- to 2.15-fold) was observed after a mild
      insult, a more pronounced longer-lasting increase (4.28- to 5.90-fold) was
      induced without overt morphological damage as the severity of injury rose above a
      certain threshold (unconscious for 200 to 250 seconds). The small short-lasting
      increase was reduced with prior administration of tetrodotoxin but not with
      cobalt, indicating that neuronal discharges are the source of this increase. In
      contrast, the larger longer-lasting increase was resistant to tetrodotoxin and
      partially dependent on Ca++, suggesting that neurotransmitter release is
      involved. In order to test the hypothesis that the release of the excitatory
      amino acid neurotransmitter glutamate mediates this increase in [K+]c, the
      extracellular concentration of glutamate ([Glu]c) was measured along with [K+]c.
      The results indicate that a relatively specific increase in [Glu]c (as compared
      with other amino acids) was induced concomitantly with the increase in [K+]c.
      Furthermore, the in situ administration of 1 to 25 mM kynurenic acid, an
      excitatory amino acid antagonist, effectively attenuated the increase in [K+]c. A
      dose-response curve suggested that a maximum effect of kynurenic acid is obtained
      at a concentration that substantially blocks all receptor subtypes of excitatory
      amino acids. These data suggest that concussive brain injury causes a massive K+
      flux which is likely to be related to an indiscriminate release of excitatory
      amino acids occurring immediately after brain injury.

PMID- 1977899
TI  - [61st Congress of the Japanese Society of Otorhinolaryngology. Tokyo, 17-19 May
      1990. Abstracts].

PMID- 1977898
TI  - Selective T-cell depletion with Ox-38 anti-CD4 monoclonal antibody prevents
      cardiac allograft rejection in rats.
AB  - New monoclonal antibodies directed to membrane molecules unique to lymphocyte
      subsets have provided the means to alter the immune response to alloantigens in a
      more selective fashion. This investigation demonstrates that monoclonal antibody
      induced depletion of CD4 helper/inducer T lymphocytes before transplantation of a
      fully mismatched heart allograft allows permanent engraftment in rats without
      further immunosuppression. Five adult male ACI (RT1a) rats received cell
      depleting doses of the mouse anti-rat CD4 monoclonal antibody, MRC Ox-38, for 1
      month before undergoing heterotopic abdominal heart transplantation. No other
      immunosuppression was administered, and immunotherapy was discontinued the day of
      transplantation. After all five Lewis rat (RT1(1)) hearts were maintained free of
      rejection for more than 3 months, a second heterotopic transplant was performed,
      this time to the femoral vessels, using either fresh Lewis heart allografts (n =
      3) or third-party, Brown-Norway (RT1n) hearts (n = 2). Histologic evaluation was
      performed 3 weeks later and revealed severe rejection of the femoral Brown-Norway
      grafts with no evidence of rejection in any of the femoral or original abdominal
      Lewis grafts. These results suggested that limited, pretransplant anti-CD4
      immunotherapy allowed permanent engraftment of fully mismatched cardiac
      allografts in rats and conferred donor-specific unresponsiveness.

PMID- 1977900
TI  - Ubiquitin conjugate immunoreactivity in the brains of scrapie infected mice.
AB  - Sections of brain from normal mice or clinically-ill mice infected with either
      the 87V or the ME7 strains of sheep scrapie were immunostained to show the
      localization of ubiquitin-protein conjugates or a specific marker of disease, the
      scrapie-associated fibril protein (PrP). In both scrapie models immunoreactive
      ubiquitin-protein conjugates were seen in thread-like structures found throughout
      the neuropil, in inclusion bodies within vacuolated neurones, and in areas
      surrounding anti-PrP positive amyloid plaques. The PrP protein was visualized in
      diffuse deposits in highly vacuolated parts of the scrapie-affected brain, and
      focally in amyloid plaques, microglia and neuronal processes. The ubiquitin
      protein conjugate staining of scrapie amyloid plaques is very similar to that
      seen in the plaques of Alzheimer's disease. The ubiquitinated intraneuronal
      inclusion bodies seen in scrapie resemble the granulovacuolar lesions also seen
      in Alzheimer's disease, but appear much larger and possibly correspond to
      material in giant autophagic vacuoles. We suggest that these inclusions may be
      the result of ubiquitinated abnormal proteins being directed to the lysosomal
      system, and that scrapie and Alzheimer's disease share at least some common
      processes of neurodegeneration.

PMID- 1977901
TI  - Time-dependent effect of melatonin on actin mRNA levels and incorporation of 35S
      methionine into actin and proteins by the rat hypothalamus.
AB  - The synthesis of the cytoskeletal protein actin exhibits, in the rat
      hypothalamus, a diurnal variation with maxima during morning hours. The objective
      of the present study was to assess whether melatonin injection could affect the
      in vitro incorporation of 35S-methionine into actin, as well as the levels of
      actin mRNA, in the hypothalamus of adult male rats treated either acutely or
      chronically with the hormone at 10:00 or 18:00. Injection of 100 micrograms/kg of
      melatonin for ten days at either time induced a significant depression in the
      incorporation of 35S-methionine into a 43 kDa protein with the electrophoretic
      mobility of actin. The specific activity of total soluble proteins after labeled
      methionine incubations decreased only after evening melatonin administration (100
      micrograms/kg, ten days). Hypothalamic actin mRNA levels, quantitated by dot-blot
      analysis, decreased only after the injection of 100 micrograms/kg melatonin for
      ten days at 10:00. Neither a 10-micrograms/kg dose of melatonin, nor a single
      injection of 100 micrograms/kg melatonin, caused any significant change in the
      parameters examined. Melatonin (100 micrograms/kg for ten days) did not modify
      hypothalamic somatostatin or H-Ras mRNA concentration. These results suggest the
      existence of an inhibitory effect of melatonin on hypothalamic actin synthesis.

PMID- 1977902
TI  - Changes in transmitter release patterns in vitro induced by tremorgenic
      mycotoxins.
AB  - The neurochemical effects of the tremorgenic mycotoxins Verruculogen and Penitrem
      A, which produce a neurotoxic syndrome characterized by sustained tremors, were
      studied using sheep and rat synaptosomes. The toxins were administered in vivo,
      either by chronic feeding (sheep) or ip injection 45 min prior to sacrifice
      (rat). Synaptosomes were subsequently prepared from cerebrocortical and spinal
      cord/medullary regions of rat, and corpus striatum of sheep. Penitrem A (400 mg
      mycelium/kg) increased the spontaneous release of endogenous glutamate, GABA, and
      aspartate by 213%, 455%, and 227%, respectively, from cerebrocortical
      synaptosomes. Verruculogen (400 mg mycelium/kg) increased the spontaneous release
      of glutamate and aspartate by 1,300% and 1,200% respectively, but not that of
      GABA, from cerebrocortical synaptosomes. The spontaneous release of the
      transmitter amino acids or other amino acids was not increased by the tremorgens
      in spinal cord/medullary synaptosomes. Penitrem A pretreatment reduced the
      Veratrine (75 microM) stimulated release of glutamate, aspartate and GABA from
      cerebrocortical synaptosomes by 33%, 46%, and 11% respectively, and the
      stimulated release of glycine and GABA from spinal cord/medulla synaptosomes by
      67% and 32%, respectively. Verruculogen pretreatment did not alter the Veratrine
      induced release of transmitter amino acids from cerebrocortex and spinal
      cord/medulla synaptosomes. Penitrem A pretreatment increased the spontaneous
      release of aspartate, glutamate and GABA by 68%, 62%, and 100%, respectively,
      from sheep corpus striatum synaptosomes but did not alter the synthesis and
      release of dopamine in this tissue. Verruculogen was shown to cause a substantial
      increase (300-400%) in the miniature-end-plate potential frequency at the locust
      neuromuscular junction. The response was detectable within 1 min, rose to a
      maximum within 5-7 min, and declined to the control rate over a similar period.
      No change in the amplitude of the m.e.p.p.s was observed. These effects of the
      tremorgens on transmitter release are interpreted in terms of their mode of
      action.

PMID- 1977903
TI  - Reduction of the N-type calcium current by noradrenaline in neurones of rabbit
      vesical parasympathetic ganglia.
AB  - 1. Intracellular and single-electrode voltage-clamp recordings were made from
      neurones of vesical parasympathetic ganglia (VPG) isolated from the rabbit
      urinary bladder. 2. Noradrenaline (NA, 0.5-5 microM) shortened the duration of
      the action potentials and depressed the amplitudes of both spike after
      hyperpolarization and after-current. 3. Voltage-dependent calcium currents (ICa)
      were recorded by using microelectrodes filled with 2 M-caesium chloride in a
      superfusing solution containing tetraethylammonium (TEA, 50 mM) and tetrodotoxin
      (TTX, 500 nM). Noradrenaline (0.5-5 microM) depressed both the ICa and the tail
      current evoked by depolarizing voltage jumps from -100 to -50 mV to -30 to +20
      mV. 4. Substitution of barium for calcium also produced an inward current (IBa)
      with no obvious tail current. Noradrenaline (1 microM) reduced the magnitude of
      the IBa without affecting the voltage dependence of the current-voltage
      relationship for IBa. 5. Yohimbine (1 microM), but not prazosin (1 microM) or
      propranolol (1 microM), antagonized the NA-induced inhibition of the IBa. UK
      14304, a potent alpha 2-adrenoceptor agonist, mimicked NA in depressing the IBa.
      6. The transient low-threshold (T), the transient high-threshold (N) and the
      slowly inactivating high-threshold (L) calcium currents co-existed in VPG
      neurones. 7. Noradrenaline reduced the IBa evoked at clamp potentials more
      positive than -20 mV from holding potentials near the resting membrane potential
      (-70 to -50 mV). Under these conditions, the IBa consisted primarily of N- and L
      current components. In contrast, NA had no effect on the isolated T- and L
      currents. It is concluded that NA selectively inhibits the N-type calcium
      channels by an action at alpha 2-adrenoceptors in the rabbit VPG neurones.

PMID- 1977905
TI  - Postoperative pain experiences: relevant patient and staff attitudes.
AB  - Postoperative pain continues to occur, despite both advances in analgesic
      techniques and recognition of the damaging effect of pain upon recovery. This
      study set out to describe the pain experiences of successive cholecystectomy
      patients in a large teaching hospital, using three different pain measures and
      self-reports of anxiety and pain-related attitudes and experiences. Nurses and
      doctors in surgical wards provided parallel information about their pain-related
      attitudes and practices. A substantial proportion of patients suffered
      significant postoperative pain, apparently related to their fear of addiction and
      reluctance to ask for extra analgesic help. Nurses were more convinced than
      patients that patients should have more control of their own pain relief.
      Barriers to effective pain relief are seen to include cognitive, attitudinal and
      systemic factors; some suggestions are offered for reform of relevant hospital
      practices.

PMID- 1977906
TI  - 3-Phenyl analogues of 2-[[[2-(2,6-dimethoxyphenoxy)ethyl]amino]-methyl]-1,4
      benzodioxan (WB 4101) as highly selective alpha 1-adrenoceptor antagonists.

PMID- 1977904
TI  - Calcium released by photolysis of DM-nitrophen stimulates transmitter release at
      squid giant synapse.
AB  - 1. Transmitter release at the squid giant synapse was stimulated by photolytic
      release of Ca2+ from the 'caged' Ca2+ compound DM-nitrophen (Kaplan & Ellis
      Davies, 1988) inserted into presynaptic terminals. 2. Competing binding reactions
      cause the amount of Ca2+ released by DM-nitrophen photolysis to depend on the
      concentrations of DM-nitrophen, total Ca2+, Mg+, ATP and native cytoplasmic Ca2+
      buffer. Measurements of presynaptic [Ca2+] changes by co-injection of the
      fluorescent indicator dye Fura-2 show that DM-nitrophen photolysis causes a
      transient rise in Ca2+ followed by decay within about 150 ms to an increased
      steady-state level. 3. Rapid photolysis of Ca2(+)-loaded nitrophen within the
      presynaptic terminal was followed in less than a millisecond by depolarization of
      the postsynaptic membrane. As with action potential-evoked excitatory
      postsynaptic potentials (EPSPs), the light-evoked response was partially and
      reversibly blocked by 1-3 mM-kainic acid which desensitizes postsynaptic
      glutamate receptors. 4. Release was similar in magnitude and rate to normal
      action potential-mediated EPSPs. 5. The release of transmitter by photolysis of
      Ca2(+)-loaded DM-nitrophen was not affected by removal of Ca2+ from the saline or
      addition of tetrodotoxin. Photolysis of DM-nitrophen injected into presynaptic
      terminals without added Ca2+ did not stimulate release of transmitter nor did it
      interfere with normal action potential-mediated release. 6. Stimulation of
      presynaptic action potentials in Ca2(+)-free saline during the light-evoked
      response did not elicit increased release of transmitter if the ganglion was
      bathed in Ca2(+)-free saline, i.e. in the absence of Ca2+ influx. Increasing the
      intensity of the light or stimulating presynaptic action potentials in Ca2(+)
      containing saline increased the release of transmitter. Therefore the failure of
      presynaptic voltage change to increase transmitter release resulting from release
      of caged Ca2+ was not due to saturation or inhibition of the release mechanism by
      light-released Ca2+. 7. Decreasing the temperature of the preparation increased
      the delay to onset of the light-evoked response and reduced its amplitude and
      rate of rise to an extent similar to that observed for action potential-evoked
      EPSPs.

PMID- 1977907
TI  - (1R,3S)-1-(aminomethyl)-3,4-dihydro-5,6-dihydroxy-3-phenyl-1H-2-benzopyran: a
      potent and selective D1 agonist.

PMID- 1977908
TI  - (R)-4-oxo-5-phosphononorvaline: a new competitive glutamate antagonist at the
      NMDA receptor complex.

PMID- 1977909
TI  - Synthesis, biological evaluation, and quantitative structure-activity
      relationship analysis of [beta-(Aroylamino)ethyl]piperazines and -piperidines and
      [2-[(Arylamino)carbonyl]ethyl]piperazines, -pyrazinopyridoindoles, and 
      pyrazinoisoquinolines. A new class of potent H1 antagonists.
AB  - Some [beta-(Aroylamino)ethyl]piperazines and -piperidines and [2
      [(Arylamino)carbonyl]ethyl]piperazines, -piperidines, -pyrazinopyridoindoles, and
      -pyrazinoisoquinolines have been synthesized and their H1-antagonistic activity
      studied in isolated guinea pig ileum. Quantitative structure-activity
      relationship analysis indicates that the hydrophobicity of the side chain of
      these compounds plays a major role in their activity while steric and electronic
      factors are of secondary importance. All these compounds act on a common receptor
      and appear to interact similarly with the receptor.

PMID- 1977910
TI  - Chemistry and pharmacology of the non-benzodiazepine anxiolytic enciprazine and
      related compounds.
AB  - In the course of studies on tranquilizers, new non-benzodiazepine-like compounds
      were synthesized. These are 1-(3,4,5-trimethoxyphenoxy)-3-[4-(2
      methoxyphenyl)piperazinyl]prop an-2-ol (INN: enciprazine) and derivatives thereof
      which were screened pharmacologically in order to evaluate their central nervous
      system activity. Compounds with marked antiaggressive and anxiolytic properties
      but without dependence potential could be detected. Enciprazine was selected for
      clinical investigations.

PMID- 1977912
TI  - Larval survey of surface water-breeding mosquitoes during irrigation development
      in the Mahaweli Project, Sri Lanka.
AB  - A survey of ground water-breeding mosquitoes was done during 1986-1987 in an area
      undergoing irrigation development in the Mahaweli Project of Sri Lanka. Forty
      nine species were collected during the 12-mo phase of humans settlement and
      infrastructure construction, and 42 species during the succeeding 12-mo period
      under irrigated rice culture. Development resulted in the elimination of some
      preexisting breeding habitats, the modification of others, and the creation of
      new habits. The overall change from uninhabited forest to settled irrigated rice
      sharply increased the prevalence of Anopheles annularis van der Wulp, An.
      peditaeniatus (Leicester), Aedeomyia catasticta Knab, Mimomyia hybrida
      (Leicester), Mansonia uniformis (Theobald), and Culex tritaeniorhynchus Giles.
      Equally sharp decreases occurred in the prevalence of An. barbirostris van der
      Wulp, An. barbumbrosus Strickland & Choudhury, Ae, jamesi (Edwards), Ae. vittatus
      (Bigot), Ae. pseudomediofasciatus (Theobald), Cx. halifaxii Theobald, Cx. malayi
      (Leicester), Cx. minutissimus (Theobald), Cx. nigropunctatus Edwards, Cx.
      fuscocephala Theobald, and Cx. mimulus Edwards. Other species that showed smaller
      positive or negative changes included An. nigerrimus Giles, An. culicifacies
      Giles, An. jamesii Theobald, An. subpictus Grassi, An. vagus Donitz, An. varuna
      Iyengar, Mi. chamberlaini (Ludlow), Ma. annulifera (Theobald), Cx.
      bitaeniorhynchus Giles, Cx. gelidus Theobald, and Cx. pseudovishnui Colless.
      Irrigation development led to reduced breeding by the majority of species;
      however, most species that did increase in prevalence were potential vectors of
      human disease. Components of the irrigation system such as reservoir and canal
      margins, seepages, and rice fields provided increased breeding sites for some of
      these species.

PMID- 1977911
TI  - Potent anticonflict activity and lessening of memory impairment with a series of
      novel [1]benzothieno[2,3-c]pyridines and 1,2,3,4-tetrahydro[1]benzothieno[2,3
      c]pyridines.
AB  - [1]Benzothieno[2,3-c]pyridines (10a-c, 11, 12a-t, and 13a,b) and 1,2,3,4
      tetrahydro[1]benzothieno[2,3-c]pyridines (3a-c, 7, 8a-c, and 9) were synthesized.
      The compounds are bioisosteres of beta-carbolines and 1,2,3,4-tetrahydro-beta
      carbolines where the indole nitrogen is replaced by sulfur. Their pharmacological
      activity was evaluated in a water lick conflict test in rats and a passive
      avoidance test in mice. In the 1,2,3,4-tetrahydro[1]benzothieno[2,3-c]pyridine
      series, the presence of ethyl ester (3b) or cyclohexyl carboxamide (7) groups at
      C-3 conferred good anticonflict activity and lessening of memory impairment,
      while N-acylation of 3b abolished activity. In the [1]benzothieno(2,3-c]pyridine
      series, the aminoethyl carboxamide (12a) group at C-3 also conferred activity,
      but other amides studied were not active. The most potent compounds (3b, 7, and
      12a) were also administered orally and had potent anticonflict and
      antiscopolamine amnesia-reversal activity. These compounds did not bind to the
      BZP receptor in spite of having structures similar to those of beta-carbolines.
      Compound 7 bound strongly to 5-HT1A receptors and would be expected to be a novel
      anxiolytic.

PMID- 1977913
TI  - Effects of house sparrow age and arbovirus infection on attraction of mosquitoes.
AB  - To test the hypothesis that arbovirus infection or advancing age increases the
      attractiveness of avian hosts to vector mosquitoes, we used an olfactometer that
      measures the response of mosquitoes to the passive, vertical diffusion of host
      related cues. St. Louis encephalitis or western equine encephalomyelitis virus
      infection in house sparrows (Passer domesticus (L.], regardless of age, had no
      detectable effect on Culex quinquefasciatus Say or Cx. tarsalis Coquillett
      attraction, respectively, at close range. Sparrow age, however, was associated
      positively with increased Cx. quinquefasciatus attraction; i.e., nestlings were
      significantly less attractive than adults, and there was a trend for increased
      mosquito attraction as nestling age increased. When birds were examined in
      groups, attraction was not equal to the sum of the individual birds in the group.
      Nestlings, either alone or in a group, were less attractive than a single adult.
      One adult plus three older nestlings were more attractive than one adult with
      three young nestlings, but no more attractive than one adult alone. We speculate
      on the epidemiological significance of these laboratory results to arbovirus
      epizootic transmission.

PMID- 1977914
TI  - Peritrophic membrane formation and cellular turnover in the midgut of Culiseta
      melanura (Diptera: Culicidae).
AB  - Midguts of the mosquito Culiseta melanura (Coquillett) were examined by light and
      electron microscopy at varying intervals after blood feeding. Peritrophic
      membrane deposition first appeared 6 h after engorgement as a thin, electron
      translucent band adjacent to epithelial cells throughout the abdominal midgut and
      reached maximum thickness at 12 h. Cell loss was apparently low in the abdominal
      midgut, with occasional cellular debris detected in the lumen 3-5 d after
      engorgement. Sloughing of cytoplasmic dropletlike evaginations, devoid of
      organelles, occurred infrequently in the abdominal midgut between 5 and 7 d after
      feeding. In contrast, cellular and cytoplasmic loss occurred continuously in the
      thoracic midgut. Epithelial cell replacement and regenerative cell mitosis were
      not detected in the abdominal or thoracic midgut.

PMID- 1977915
TI  - Patterns of eastern equine encephalomyelitis virus infection in Culiseta melanura
      (Diptera: Culicidae).
AB  - Infection of the mosquito Culiseta melanura (Coquillett) by eastern equine
      encephalomyelitis virus was examined using transmission electron microscopy (TEM)
      of whole tagmata and fluorescent antibody assay (FA) and infectious assay (IA) of
      dissected tissues. Following infectious blood meals from chicks circulating
      different virus titers, mosquitoes were examined after extrinsic incubation
      intervals of 1-22 d. Virus was first detected by FA and IA in midguts and
      nonalimentary tissues 24 h after infection. Nascent virus was first visualized by
      TEM in several tissues, including midgut, fat body, and salivary glands, of high
      titer-infected mosquitoes 48 h after they engorged. Moderate- and low-titer blood
      meals resulted in slightly slower appearance and dissemination of virus. Results
      were consistent with dissemination of virus from the posterior midgut to salivary
      glands via the hemolymph. Neural tissues contained little or no virus, whereas
      fat body appeared to be an important organ for virus replication and
      dissemination. Dissemination barriers did not accompany mosquito infections.

PMID- 1977916
TI  - Genetic analysis of treated and untreated phenylketonuria in one family.
AB  - We describe a family in which four subjects in two generations have a disorder of
      phenylalanine metabolism. Two first cousins had different biochemical
      presentations in the neonatal period. The older child was thought to have a more
      severe form of phenylketonuria (PKU), and the younger child a milder form. While
      carrying out family studies we discovered that their mutual grandfather and his
      older unmarried brother, both of normal intelligence, had a marked and previously
      undiagnosed hyperphenylalaninaemia. DNA analysis using RFLP haplotypes has shown
      that there are four independent mutant PKU alleles in this family which are found
      on three haplotype patterns. None of the affected family members carries a
      previously defined mutation at the phenylalanine hydroxylase (PAH) locus and so
      DNA analysis was not able to explain the apparently different biochemical
      phenotypes in the affected members of this family.

PMID- 1977917
TI  - Diversity of staphylococci exhibiting high-level resistance to mupirocin.
AB  - Plasmids mediating high-level resistance to mupirocin (MIC greater than 1000
      mg/L) in staphylococci from various sources were studied by restriction
      endonuclease cleavage. Several patterns were obtained but six plasmids isolated
      from various Staphylococcus aureus and S. epidermidis strains were
      indistinguishable. The diversity and spread of these plasmids is illustrated.

PMID- 1977918
TI  - Cellular immune response of SIV-infected rhesus macaques.
AB  - Optimal conditions for the assessment of T cell proliferation and cytolytic T
      lymphocyte (CTL) responses specific for primate lentivirus were established. CTL
      and T cell proliferative responses were demonstrated as early as two weeks post
      infection. Although the majority of CTL were CD8+, MHC class I-restricted, this
      study demonstrated CD4+, MHC class II-restricted CTL. Experiments also
      demonstrated that CTL were CD16 negative. Target cell generation could be blocked
      with CD4 mAb specific for the SIV binding site.

PMID- 1977919
TI  - Molecular clones of SIVsm and SIVagm: experimental infection of macaques and
      African green monkeys.
AB  - We have investigated the ability of biologically-active proviral molecular clones
      of SIVsm and SIVagm to infect rhesus macaques, pig-tail macaques, and African
      green monkeys. Two clones of SIVsm were individually inoculated into four rhesus
      and four pig-tail macaques. All eight macaques became infected, and two have
      experienced a significant decline in absolute numbers of circulating CD4+ cells.
      None of three African green monkeys were infected by an SIVsm molecular clone.
      However, one of four African green monkeys did become infected by SIVsm after
      receiving lymphocytes directly from an SIVsm-infected rhesus macaque. A molecular
      clone of SIVagm infected three of four macaques and three of three African green
      monkeys. None of the three infected macaques had a significant decline in
      circulating CD4+ cells. Interestingly, infection of pig-tail macaques (but not
      rhesus macaques) with uncloned SIVagm induced a significant drop in circulating
      CD4+ cells. These data suggest that molecular clones of SIVsm and SIVagm can be
      used in experimental models of AIDS for the evaluation of viral gene functions
      and for the study of in vivo genetic variation.

PMID- 1977921
TI  - Endocardial endothelium mediates positive inotropic response to alpha 1
      adrenoceptor agonist in mammalian heart.
AB  - Although the positive inotropic response to alpha 1-agonists has been well
      documented, the mechanism is incompletely understood. In isolated papillary
      muscle of cat and rabbit, low physiological concentrations of phenylephrine (PE)
      (10(-9)-10(-7) M; 35 degrees C) under beta-blockade (propranolol 10(-6) M) and in
      physiological [Ca2+]o (1.25 mM), significantly increased peak twitch tension (TT)
      with typical unchanged or slightly prolonged twitch contraction duration. This
      typical response necessitated the presence of an intact endocardial endothelium
      (EE) since no inotropic response was observed at or below 10(-7) M PE in muscles
      where the EE had been damaged by 1 s exposure to 1% Triton X-100 prior to the
      first PE addition. After Triton-induced EE damage prior to the first PE addition,
      a direct myocardial inotropic response could be demonstrated, but this response
      required higher concentrations of PE (10(-6)-10(-3) M) and was significantly less
      pronounced than in muscles with intact EE. At elevated (2.5 mM) or high (7.5 mM)
      Ca2+, a concentration dependent inotropic response to PE could be induced at the
      higher concentrations of PE (10(-6) M or higher), but the inotropic response to
      low concentrations of PE (10(-7) M or below) was absent even in the presence of
      an intact EE. In papillary muscles with intact EE at physiological [Ca2+]o of
      1.25 mM, the higher concentrations of PE (10(-6) M or higher) destroyed the EE.
      Indeed, after washing with fresh bathing solution following prolonged exposure to
      these high concentrations of PE, the baseline twitches resembled twitches in
      muscles where the EE had been experimentally damaged. Selective destruction of
      the EE by PE in these conditions with no morphological damage to the subjacent
      myocardium was confirmed on electron microscopy. A second concentration-response
      curve to PE was significantly depressed, shifted to the right and with no
      response at or below 10(-7) M PE. Subsequent successive curves were not
      significantly different from the second one. At the higher Ca2+ (2.5 mM or 7.5
      mM), neither functional nor morphological evidence of damage to the EE was
      observed regardless of the PE concentration and exposure time; in some muscles EE
      damage did occur at high Ca2+, however, but only after multiple exposures to high
      PE each followed by abundant wash. At all concentrations of PE, the alpha 1
      antagonist prazosin (10(-5) M) blocked the inotropic response regardless of
      [Ca2+]o and prevented morphological endothelial damage at 1.25 mM Ca2+.

PMID- 1977920
TI  - Sulfate self-exchange and amino acid transport in calcium-loaded human
      erythrocytes.
AB  - To analyze the effects of Ca2(+)-mediated membrane protein changes on the
      membrane function, we have studied the SO4(2-) self-exchange and amino acid
      transport in human erythrocytes after loading them with Ca2+ with the help of
      ionophore A23187. The SO4(2-) self-exchange is inhibited by 20-30% by loading the
      erythrocytes with 25 microM to 0.5 mM Ca2+. The extent of this inhibition is
      almost doubled (50-60%) by increasing the Ca2+ loading concentration to 1.5 mM.
      This additional effect of 1.5 mM Ca2+ is not correlated with the Ca2(+)-induced
      ATP depletion or membrane protein degradation, but is caused by the
      transglutaminase-catalyzed membrane protein crosslinking. Like the SO4(2-) self
      exchange, L-alanine and L-cysteine uptakes are also inhibited in Ca2(+)-loaded
      cells. However, no effect is observed on the L-lysine uptake under identical
      conditions. These results have been interpreted to suggest that the Ca2(+)
      mediated effects on the SO4(2-) self-exchange and amino acid transport are caused
      perhaps by the Ca2(+)-induced structural rearrangement of the band 3 protein.

PMID- 1977922
TI  - Electrophysiological characterization of cardiac beta 2-adrenoceptors in sheep
      Purkinje fibers.
AB  - The electrophysiological effects mediated by beta 2-adrenoceptor stimulation were
      studied in sheep cardiac Purkinje fibers. beta 2-Adrenoceptor stimulation was
      achieved by using isoproterenol (ISO) in the presence of the highly selective
      beta 1-antagonist CGP 20712A. ICI 118,551 was used as a selective beta 2
      antagonist. In driven preparations, ISO (0.1 to 1 microM) caused a positive
      inotropic effect which was associated with the shortening of action potential
      duration and was completely abolished only by the simultaneous presence of CGP
      20712A (0.3 microM) and ICI 118,551 (50 nM). In previously quiescent
      preparations, ISO (0.1 to 1 microM) induced spontaneous activity in 15 out of 24
      preparations. In the presence of CGP 20712A (0.3 microM) only five preparations
      out of 24 became automatic when exposed to ISO, and their rate of firing was
      significantly reduced (13 +/- 4 vs. 43 +/- 6 beats/min, P less than 0.05) with
      respect to ISO alone. CGP 20712A completely abolished the steepening of diastolic
      depolarization and the increase of the pacemaker current caused by ISO (0.1 to 1
      microM). The beta 2-antagonist ICI 118,551 (50 nM) completely failed to modify
      the effect of ISO on the rate of spontaneous firing, the slope of diastolic
      depolarization and the pacemaker current. On the other hand, the increase of
      oscillatory afterpotential (OAP) amplitude caused by ISO in strophanthidin
      treated preparations was significantly reduced only by the beta 1-antagonist CGP
      20712A, but not by the beta 2-antagonist ICI 118,551. These results demonstrate
      that beta 2-adrenoceptors are functionally present in sheep Purkinje fibers where
      their stimulation consistently causes a positive inotropic effect. However, beta
      2-adrenoceptors do not appear to affect the processes of normal automaticity, and
      do not greatly contribute to triggered activity due to OAPs.

PMID- 1977923
TI  - Effects of alpha-adrenergic agents on generation of oscillatory afterpotentials
      and triggered activity in rabbit Purkinje fibers.
AB  - Effects of alpha 1- and alpha 2-adrenergic agonists and antagonists on
      oscillatory afterpotentials (OAP) and triggered activity induced by
      acetylstrophanthidin (AS) or 8 mM Ca2+ (with 2 mM K+) were studied with standard
      microelectrode techniques in isolated rabbit heart Purkinje fibers. Experiments
      were conducted in the presence of 0.5 microM propranolol. Phenylephrine (PE, 0.5
      to 10 microM) increased the amplitude of OAP and induced triggered activity when
      subthreshold OAP were caused by high Ca2+. In contrast, PE decreased the
      amplitude of OAP and suppressed triggered activity induced by
      acetylstrophanthidin. Prazosin at 0.5 microM did not affect the amplitudes of OAP
      by itself, but abolished both the inhibitory effect of PE on AS-induced OAP and
      the stimulatory effect of PE on high Ca2(+)-induced OAP. At 2 microM, prazosin
      alone reduced the amplitude of OAP and suppressed triggered activity induced by
      either acetylstrophanthidin or high Ca2+. While clonidine (0.5 to 10 microM) did
      not affect OAP or induction of triggered activity, yohimbine (2 microM) decreased
      the amplitude of OAP and abolished triggered activity induced by either
      acetylstrophanthidin or high Ca2+. Thus, specific alpha 1-adrenergic actions of
      phenylephrine may exert either pro-arrhythmic or antiarrhythmic effects on OAP
      and triggered activity depending on the method of induction of OAP. The alpha 1-
      and alpha 2-antagonists prazosin and yohimbine both exert direct antiarrhythmic
      effects in addition to their adrenergic blocking actions.

PMID- 1977925
TI  - Toxicity of 6-hydroxydopamine and dopamine for dopaminergic neurons in culture.
AB  - Toxicity of 6-hydroxydopamine (6-OHDA) and dopamine were studied in cultures of
      dissociated fetal rat mesencephalic cells. To assess survival and function of
      dopaminergic cells we quantified the number of tyrosine hydroxylase-positive
      cells and measured dopamine uptake. Non-dopaminergic cells were monitored by
      counting the number of cells visible with phase-contrast microscopy and measuring
      GABA uptake. 6-OHDA, in contrast to MPP+, which selectively destroyed
      dopaminergic neurons, was found to be a non-selective neurotoxin in this culture
      system. Between 10 and 100 microM, dopaminergic and non-dopaminergic cells were
      destroyed. At concentrations higher than 100 microM, i.e., concentrations
      frequently used to lesion catecholaminergic neurons in vivo, 6-OHDA resulted in
      structural fixation and loss of viability of dopaminergic and non-dopaminergic
      cells. Dopamine produced the same actions at slightly higher concentrations. One
      hundred to 300 microM was toxic for all cell types, and concentrations above 300
      microM resulted in fixation. The findings suggest that 6-OHDA cannot be
      considered a selective toxin for catecholaminergic neurons in vitro. The
      demonstrated toxicity of dopamine tends to support speculations that processes
      related to dopamine metabolism may play a role in the pathogenesis of Parkinson's
      disease.

PMID- 1977924
TI  - Expression of the MDR1 gene in human gastric and colorectal carcinomas.
AB  - We measured expression of the MDR1 gene (also known as the PGY1 gene) in the
      human gastrointestinal tract. MDR1 messenger RNA (mRNA) levels were elevated in
      13 of 15 colorectal carcinoma specimens and in six of 13 gastric carcinoma
      specimens. Well-differentiated colorectal carcinomas contained significantly
      higher concentrations of MDR1 mRNA than moderately differentiated colorectal
      carcinomas. Similarly, moderately differentiated gastric carcinomas contained
      higher concentrations of MDR1 mRNA than poorly differentiated gastric carcinomas.
      MDR1 gene expression in normal colorectal and gastric tissues adjacent to
      carcinomas was similar to that in the carcinomas. MDR1 gene expression in
      xenografts of colorectal and gastric carcinomas in nude mice was also
      investigated. Elevated expression of the MDR1 gene was seen in only four of 18
      xenografts of colorectal carcinoma and was not seen in any xenografts of gastric
      carcinoma. P-glycoprotein was distributed over the luminal surface of the
      colorectal carcinoma. These results imply that the higher levels of MDR1 mRNA
      found in well-differentiated carcinomas derived from colorectal tissues are the
      results of increased expression of the MDR1 gene in the luminal surface cells.
      The level of expression of the MDR1 gene in colorectal and gastric carcinomas
      appears to correlate with the degree of differentiation and also appears to be
      affected by transplantation into nude mice.

PMID- 1977926
TI  - Effects of short- and long-term ganglioside treatment on the recovery of
      neurochemical markers in the ibotenic acid-lesioned rat striatum.
AB  - The striatum of adult rats was bilaterally lesioned with stereotaxic injections
      of ibotenic acid in a dose (16 nmoles) that resulted in subtotal lesions. Some
      rats received systemic ganglioside treatment starting the day before operation
      and lasting for 6 or 24 days after operation; they were compared with lesioned
      rat receiving systemic saline injections as well as with corresponding groups of
      sham-operated animals. Specific neurochemical markers for cholinergic neurons
      (choline acetyltransferase, ChAT), GABAergic neurons (glutamate decarboxylase;
      GAD), and astrocytes (glutamine synthetase; GS) were assayed to asses the
      neurochemical recovery promoted by ganglioside treatment. Twenty-four, but not
      six, days after operation a significant increase of ChAT and GAD was measured in
      the striatum of lesioned rats treated with gangliosides in comparison with the
      saline group. Furthermore, a significant increase of both enzymes occurred in the
      striatum of lesioned rats receiving ganglioside treatment for 24 days in
      comparison with rats receiving ganglioside treatment for 6 days only. A small but
      significant increase of ChAT was measured in the striatum of sham-operated rats
      after 24 days of ganglioside treatment in comparison with the corresponding
      saline group. Finally, the increase of GS caused by the glial reaction to the
      ibotenic acid lesion was not affected by ganglioside treatment. The results
      indicate that a relatively long-lasting ganglioside treatment stimulates the
      recovery of specific neuronal transmitter markers and that some effect is, in
      addition, exerted on unlesioned cholinergic striatal neurons.

PMID- 1977927
TI  - Glutathione and related enzymes in fascioliasis before and after treatment with
      bithionol.
AB  - The present work is an update evaluation of the glutathione status in patients
      with established fascioliasis before and after treatment with bithionol. Blood
      glutathione (GSH), erythrocyte glutathione S-transferase (GST) and serum gamma
      glutamyl transferase (GGT) activities were studied. After treatment, the
      variations observed in these parameters were restored to the corresponding normal
      control values confirming the toxic features resulting from fascioliasis and
      suggesting no adverse effect of bithionol on the parameters studied. We recommend
      the use of serum GGT, blood GSH and erythrocyte GST for the early detection of
      therapeutic response in fascioliasis.

PMID- 1977928
TI  - Urinary excretion of Tamm-Horsfall protein in women with recurrent urinary tract
      infections.
AB  - Since MS-fimbriated bacteria adhere to Tamm-Horsfall protein, it has been
      suggested that Tamm-Horsfall protein may trap urinary pathogens and prevent them
      from colonizing the mucosal surfaces of the urinary tract. To test the hypothesis
      that low urinary Tamm-Horsfall protein excretion rates predispose to urinary
      tract infection we obtained serial urine samples from 17 women with and 18
      without a history of recurrent urinary tract infection. None of the women had
      known structural abnormalities of the urinary tract. Concentrations of Tamm
      Horsfall protein in urine were measured with a sensitive enzyme-linked
      immunosorbent assay method. On the average, 3 urine samples per person collected
      within 3 to 6 months were analyzed. The mean Tamm-Horsfall protein excretion of
      women with recurrent urinary tract infection was 57.0 mg./l. and that of controls
      was 66.3 mg./l.; this difference was not statistically significant. The mean
      coefficient of variation was 44.2 and 62.1%, respectively. We conclude that
      urinary Tamm-Horsfall protein concentration is not significantly decreased in
      women with recurrent urinary tract infection compared with controls, and that
      excretion varies widely in repeat samples obtained from the same individual.

PMID- 1977929
TI  - Laparoscopy for the nonpalpable testis: how to interpret the endoscopic findings.
AB  - We evaluated by laparoscopy 38 patients with 45 nonpalpable testes. Of 24 testes
      identified in the abdominal cavity 15 were atrophic, 2 had no epididymal
      connection and 7 were normal in appearance. Of the 38 patients 32 (84.2%)
      underwent exploration. A correlation of 100% occurred between laparoscopy and
      surgery concerning the presence or absence of the testis. Of the testes sought
      60% were present (all but 1 in the abdomen) and 40% were absent. We conclude that
      diagnostic laparoscopy is as effective as exploration in adults and children,
      with a low risk of complication.

PMID- 1977930
TI  - Polyarteritis nodosa masquerading as a primary testicular neoplasm: a case report
      and review of the literature.
AB  - We report a case of polyarteritis nodosa presenting as a mass in the testis
      mimicking a neoplasm. The diagnosis was confirmed by radical orchiectomy. This is
      an unusual presentation of this systemic disease. We discuss the physical
      findings, ultrasonographic features and pathological findings, as well as review
      the literature for previous similar cases.

PMID- 1977931
TI  - Effects of intracavernosal trazodone hydrochloride: animal and human studies.
AB  - Trazodone hydrochloride is an oral antidepressant agent which has been associated
      with the improvement of erections in impotent men and the development of
      prolonged erections or priapism in potent men. An in vivo study in animal and
      human subjects was performed to gain experience with the effect of
      intracavernosal trazodone. In the anesthetized New Zealand White rabbit,
      intracavernosal trazodone or its major metabolite m-chlorophenylpiperazine (m
      CPP) produced full penile erection in 76% and 84% of animals studied respectively
      with doses ranging from one to 15 mg. On the other hand, intracavernosal
      administration of five mg. papaverine resulted in a prolonged erection in 90% of
      animals studied. In 13 selected volunteer patients, intracavernosal trazodone
      caused tumescence but not full penile erection with corporal body pressures of
      28.2 +/- 5.8 mm. Hg. Intracavernosal papaverine or papaverine and phentolamine in
      these subjects resulted in significantly higher corporal body pressures of 58 +/-
      18 mm. Hg (p less than .05). Intracavernosal administration of alpha adrenoceptor
      agonists but not normal saline resulted in complete detumescence of trazodone- or
      m-CPP-induced prolonged erection in the animal studies. Intracavernosal trazodone
      results in erectile activity that appears in part based on its local alpha
      blocking activity but like other intracavernosal alpha-blocking agents is not as
      effective in initiating penile erections as are intracavernosal agents that
      directly induce smooth muscle relaxation.

PMID- 1977932
TI  - The effect of an alpha-2 agonist on bladder function and cord histology after
      spinal cord injury.
AB  - Spinal injury in cats is accompanied by urinary bladder and hind limb
      dysfunction. Ten cats subjected to spinal contusion at the ninth thoracic segment
      were treated with guanabenz (an alpha-2 agonist) intraperitoneally (0.65 mg./kg.)
      three hours after injury, and twice daily for eight weeks. An additional six
      spinal cats were untreated and served as controls. Urodynamic studies were
      performed on a weekly basis on all animals. Guanabenz modified the vesico-somatic
      reflex: detrusor-sphincter dyssynergia was either ablated or abolished. In
      contrast, the controls demonstrated detrusor-sphincter dyssynergia, high residual
      urine, and spasticity below the lesion. Histological evaluations of the spinal
      cords revealed that the six paraplegic animals (untreated) suffered marked
      cavitation of the cord and complete destruction of the grey matter. The five
      incomplete paraplegic animals (treated) showed minimal cavitation with some
      preservation of the grey matter. The five ambulators (treated) demonstrated some
      distortion of grey matter with preservation of white matter. Treatment with
      guanabenz post traumatic cord injury results in decreased cord cavitation.
      Detrusor-sphincter dyssynergia is diminished and hind limb function is improved
      in treated animals.

PMID- 1977933
TI  - Surrogate markers of disease studied as means of determining AIDS drugs'
      effectiveness.

PMID- 1977934
TI  - New pharmaceutical strategies devised in effort to treat schizophrenia
      effectively with less risk.

PMID- 1977935
TI  - Torsades de pointes occurring in association with terfenadine use.
AB  - Torsades de pointes is a form of polymorphic ventricular tachycardia that is
      associated with prolongation of the QT interval. Although found in many clinical
      settings, torsades de pointes is most often drug induced. This report describes
      the first association (exclusive of drug overdose) of symptomatic torsades de
      pointes occurring with the use of terfenadine in a patient who was taking the
      recommended prescribed dose of this drug in addition to cefaclor, ketoconazole,
      and medroxyprogesterone. Measured serum concentrations of terfenadine and its
      main metabolite showed excessive levels of parent terfenadine and proportionately
      reduced concentrations of metabolite, suggesting inhibition of terfenadine
      metabolism. We believe that a drug interaction between terfenadine and
      ketoconazole resulted in the elevated terfenadine levels in plasma and in the
      cardiotoxicity previously seen only in cases of terfenadine overdose.

PMID- 1977936
TI  - The Snowbird Conference on Nutritional Pharmacology. Proceedings.

PMID- 1977937
TI  - Regression of left ventricular hypertrophy in hypertensive patients: responses to
      exercise by antihypertensive treatment.
AB  - The effects of various antihypertensive treatments on the echocardiographic and
      electrocardiographic findings of left ventricular (LV) hypertrophy were studied
      in 75 patients with essential hypertension. The hemodynamic effects of the
      therapy during exercise were also compared. LV mass by echocardiogram was
      significantly reduced by beta-blockade and angiotensin converting enzyme
      inhibition (ACEI), but only slightly reduced by Ca channel blockade. QRS high
      voltage criteria of LV hypertrophy by electrocardiogram were reduced by all 3 of
      these antihypertensive treatments. At submaximal exercise, the pressor responses
      were attenuated by captopril, but not influenced by metoprolol or nifedipine. The
      increase in plasma norepinephrine by exercise was significantly suppressed after
      captopril, but was somewhat augmented after metoprolol or nifedipine. These
      observations indicate that the responses of hemodynamics and sympathetic nervous
      activity to exercise are different after the treatment by beta-blocker, Ca
      channel blocker or ACEI, in spite of the equal antihypertensive effect. However,
      it is suggested that the regression of LV hypertrophy might be induced by
      antihypertensive therapy, though the different grade by the individual drug.

PMID- 1977938
TI  - Intracerebroventricular injections of endothelin increase arterial pressure in
      conscious rats.
AB  - We investigated the possible effects of endothelin (ET) on the central regulation
      of arterial pressure by injecting ET intracerebroventricularly (ICV) into
      conscious rats. ICV injections of ET caused dose-dependent elevation of arterial
      pressure and increase of heart rate. The first reaction was abolished by
      bunazosin, an alpha 1-adrenergic blocker, injected intravenously. However, the
      increase in arterial pressure and heart rate caused the rats, injected with ET
      ICV, to roll to the left on their long axis for 20-30 min, followed by prolonged
      sedation. Furthermore, the pressor responses and tachycardia were significantly
      attenuated by the ICV pretreatment with nicardipine, a calcium channel blocker,
      and nicorandil, a nitrate derivative, respectively. These results suggest that ET
      may elevate the intracellular Ca2+ concentration ([Ca2+]i) of sympathetic nerve
      activity regulatory neurons of the brain, leading to an accelerated outflow of
      sympathetic nerve activity and cause the elevation of arterial pressure.

PMID- 1977939
TI  - Evaluation of a new vasodilating beta-blocking agent, carvedilol, in exertional
      angina using holter monitoring.
AB  - Antianginal and antiischemic effects and clinical pharmacologic actions of
      carvedilol, a novel beta-blocking agent with a vasodilator action, were
      determined by Holter electrocardiographic monitoring in 13 patients with
      exertional angina. The patients were observed for 1 week prior to entry into the
      study, followed by 1 to 2 weeks of treatment with carvedilol. During the
      observation period the patients received one placebo tablet daily, and during the
      treatment period one 20 mg tablet of carvedilol daily. Before and after the
      treatment 24-hour Holter electrocardiographic tracings were obtained. The mean
      interval of Holter monitoring was 11.2 +/- 4.5 days for the observation and
      treatment periods, and the mean time of drug administration was 8:25 a.m. (+/- 30
      min). The Holter electrocardiographic tracings which were obtained twice in 9
      patients during the observation period showed a high degree of reproducibility
      with respect to the frequency, magnitude and duration of ST-segment depression.
      The total frequency of ST depression per patient was 4.5 +/- 3.4 events/day pre
      drug and 2.1 +/- 2.1 events/day post-drug. There was a significant reduction in
      total frequency of ST depression post-drug (p less than 0.01). The frequency of
      asymptomatic ST depression was similarly decreased post-drug (p less than 0.01),
      and the total magnitude and duration of ST depression were significantly improved
      post-drug (p less than 0.01 and p less than 0.05, respectively). These effects of
      carvedilol lasted for 24 hours after administration. Considering that the heart
      rate was not excessively reduced during the night, and nocturnal myocardial
      ischemic episodes were not exacerbated, the mode of action of this drug seems to
      be based on not only a beta-blocking action but also on a vasodilator action.
      Carvedilol benefits exertional angina when used in a 20 mg s.i.d. regimen.

PMID- 1977940
TI  - [An autopsy case of extra-adrenal malignant pheochromocytoma].
AB  - An autopsy case of an extra-adrenal malignant pheochromocytoma in a 34-year-old
      woman is reported. On laparotomy, many advanced stage malignant tumors
      originating from the paraganglia along the abdominal aorta were found to have
      invaded the lumbar vertebrae. After a partial resection, Co60 radiation therapy
      of the paraganglia was instituted, as well as of the metastatic lesions, with
      little effect. It was found that alpha-methyl-tyrosine was effective in
      controlling the plasma catecholamine, but had to be discontinued because of an
      untoward effect (anxiety). The patient subsequently developed intractable
      hypertension and a paralytic ileus from excess catecholamine secretion. As an
      alpha 1 adrenergic blocker was not effective, we had to use large doses of
      phentolamine to control these complications. Despite various intensive therapies,
      however, the patient died of heart failure resulting from 4 years of severe
      hypertension.

PMID- 1977941
TI  - [Major histocompatibility and bone marrow transplantation].

PMID- 1977942
TI  - [Progress in confirmation of bone marrow engraftment and analysis of
      hematopoietic chimerism].

PMID- 1977943
TI  - [DNA diagnosis in medicine].
AB  - About 950 genes (or a part of them) have been cloned. Using them as probes, DNA
      diagnosis is now available in hundreds of hereditary diseases and some malignant
      diseases. In many of them, detailed analysis into the mechanisms underlying the
      diseases has become possible. Examples of this capability include 21 hydroxylase
      deficiency, amyloid polyneuropathy, Duchenne/Becker muscular dystrophy, and CML.
      About one third of the cloned genes show RFLPs (restriction fragment length
      polymorphisms). In addition "random" DNA fragments have been cloned, many of them
      can also be used to detect RFLPs. An RFLP study has proven very useful in the
      preclinical/prenatal diagnosis of hereditary diseases even though gene-action is
      unknown (e.g., Huntington disease and von Recklinghausen disease). DNA diagnosis
      has also been found to be very useful in the detection of microorganisms, minute
      chromosome changes (e.g., XX males) and for forensic purposes. The techniques and
      understanding of DNA diagnosis have become mandatory in many areas of medicine.

PMID- 1977944
TI  - [37th congress of the Japanese Society of Clinical Pathology. Tokyo, 14-16
      October 1990. Abstracts].

PMID- 1977945
TI  - [Role of vagus nerve for release of gut hormones].
AB  - The role of vagus nerve for release of gastrin, secretin and somatostatin in dogs
      was studied. Bilateral cervical vagotomy and electric vagal stimulation (25 V 0.5
      msec 10 Hz) were performed and blood levels of gut hormones were measured. After
      vagotomy, blood levels of gastrin, secretin and somatostatin did not change. The
      electric vagal stimulation elevated blood level of gastrin. Atropine and
      hexamethonium inhibited the elevation. The electric vagal stimulation did not
      change blood levels of secretin and somatostatin. In conclusion, vagal
      stimulation releases gastrin into blood circulation depending on the cholinergic
      mechanism.

PMID- 1977946
TI  - [30th congress of the Japanese Society of Nuclear Medicine. Tokyo, 14-16 November
      1990. Abstracts].

PMID- 1977947
TI  - Massive pulmonary hemorrhage in polyarteritis nodosa (PN); report of a case.
AB  - We report a case of massive pulmonary hemorrhage which emerged in the course of
      polyarteritis nodosa (PN). Pulmonary hemorrhage was the major manifestation which
      determined the mortality of this patient, though severe renal failure
      concurrently developed. The diagnosis of PN should be considered in all cases of
      pulmonary hemorrhage coexisting with renal failure. As pulmonary hemorrhage can
      be life-threatening, early diagnosis is essential for the prompt start of
      adequate therapy.

PMID- 1977948
TI  - [The influence of serum theophylline concentration on the bronchodilating effect
      of salbutamol inhalation for bronchial asthma].
AB  - To examine the effects of serum theophylline concentration on the bronchodilating
      effect of beta 2-stimulant inhalated by patients with bronchial asthma, 200
      micrograms-Salbutamol inhalation test was performed on 30 patients with bronchial
      asthma (from 17 to 71 years old, averaging 49.7; 3 mild, 15 moderate, 12 severe),
      who had taken theophylline at various oral doses up to 6 hours before the test.
      Measurements of respiratory function, serum theophylline concentration, blood
      pressure, pulse rate and the plasma c-AMP and c-GMP concentrations before and one
      hour after inhalation revealed that inhalation of 200 micrograms salbutamol
      significantly increased FVC, FEV1.0, PEF and plasma c-AMP (p less than 0.001). No
      significant change was noted in plasma c-GMP, diastolic pressure or pulse rate.
      Systolic pressure significantly decreased (p less than 0.05). Furthermore, no
      significant correlation was noted between the rates of increase (%) in FVC,
      FEV1.0 and PEF and those in plasma c-AMP, c-GMP and c-AMP/c-GMP in one hour after
      inhalation. Inaddlition no significant correlation was noted between the rates of
      increase in FVC, FEV1.0 and PEF one hour after inhalation and serum theophylline
      concentrations (0-19.3 and 0-21.5 micrograms/ml before and one hour after
      inhalation, respectively). The above results suggest that the bronchodilating
      effect of salbutamol inhalated at dose of 200 micrograms is not influenced by the
      serum theophylline concentration both before and at one hour after inhalation of
      salbutamol. The bronchodilating effect of salbutamol seems to be ascribable to an
      increase of intracellular c-AMP level of bronchial smooth muscle.

PMID- 1977949
TI  - [A clinical trial to determine whether intravenous aminophylline is indispensable
      in the treatment of status asthmaticus].
AB  - In Japan, intravenous aminophylline (AMP) is considered as the first treatment of
      choice for status asthmaticus, whereas inhaled beta 2-agonist is considered to be
      of no value for acute severe asthma. To determine the optimal therapy for acute
      asthma, the authors clinically investigated bronchodilating effects and the
      clinical role of aerosolized beta 2-agonist inhalation and intravenous AMP in 55
      patients with status asthmaticus. Patients were classified into two groups
      treated without intubation and with artificial ventilation. Intravenous steroid
      (equivalent to 4 mg/kg of hydrocortisone) was administered in all cases. Further,
      all patients were randomly divided into two subgroups according to treatment
      regimen, i.e. repeated inhalation of aerosolized beta 2-agonists only, and
      combined with intravenous AMP. In all groups, the duration of treatment was
      significantly shorter in the subgroups treated with repeated aerosolized beta 2
      agonist inhalation than those treated with intravenous AMP. The failure of
      intravenous AMP to effect more rapid or profound improvement both in objective
      and subjective parameters suggested that inhaled beta 2-agonist with intravenous
      steroid should be a rational choice in the initial treatment of acute asthma.
      Moreover, inhaled beta 2-agonist used optimally produces good bronchodilation
      several times greater than that produced by intravenous AMP. We concluded that
      repeated inhalation of aerosolized beta 2-agonists is the drug of choice combined
      with intravenous steroid regardless of the severity of attacks for short-term
      therapy of acute severe asthma, and that intravenous AMP may have only minor
      bronchodilating effects.

PMID- 1977951
TI  - [Microsurgical autotransplantation of undescended testis].

PMID- 1977950
TI  - Differing regulation and function of ICAM-1 and class II antigens on renal
      tubular cells.
AB  - Intercellular adhesion molecule-1 (ICAM-1) and MHC class II (Ia) antigens are
      increased on proximal tubular epithelial cells (TEC) in autoimmune nephritis and
      transplant rejection. ICAM-1 is a member of the immunoglobulin gene superfamily
      that increases the avidity of T cell interactions with antigen-presenting cells
      bearing Ia antigens. Using an existing mAb and cDNA probe for Ia antigen, and a
      newly described mAb (YN1/1.7.4) and cDNA probe for murine ICAM-1, we compared
      mRNA transcript levels, surface expression and function of these molecules in
      transformed TEC derived from normal (C3H/FeJ) and autoimmune (MRL-lpr) mice. No
      differences were found on TEC between these strains of mice. Stimulation of TEC
      with interferon-gamma (IFN-gamma) resulted in the expression of Ia antigens, and
      a marked increase of ICAM-1 from basal levels. Increases in ICAM-1 levels
      occurred with concentrations of IFN-gamma 10 to 100 times lower (0.5 to 1.0 U/ml)
      than those required for Ia expression, and preceded Ia antigen expression by more
      than 48 hours. Anti-ICAM-1 mAb lowered the binding and antigen-presenting ability
      of TEC to the A2A2 T cell hybridoma, suggesting a role for ICAM-1 in immune
      interactions between TEC and T cells. Dexamethasone treatment of MRL-lpr mice
      abrogated the increase of Ia antigens found in the kidneys of nephritic mice yet
      did not reduce the expression of ICAM-1 in either kidneys or cultured stimulated
      TEC. We conclude that elevated ICAM-1 expression on TEC increases the immune
      accessory cell capability of TEC bearing Ia antigens, and is resistant to down
      regulation by some immunosuppressive agents.

PMID- 1977952
TI  - [Risk factors in systemic vasculitis].

PMID- 1977953
TI  - [Effect of glucocorticoid hormones on the status of the hypothalamo-hypophyseal
      adrenal system and endocrine function of the pancreas in patients with
      hemorrhagic fever with renal syndrome].
AB  - HFRS-related oliguria brings about hyperactivity of the system hypothalamus
      hypophysis-adrenals and hyperfunction of the pancreas; glucose, urea and
      creatinine plasma levels are elevated. Prednisolone treatment leads to diminution
      of ACTH and cortisol levels, elevation of glucose, insulin and C-peptide
      concentrations in plasma compared to prednisolone-untreated patients, producing
      insignificant effect on plasma levels of STH, vasopressin, aldosterone, area and
      creatinine. Therefore, a course administration of glucocorticoids to HFRS
      patients is justified only in severe collapses and hypopituitary coma confirmed
      by the laboratory methods.

PMID- 1977954
TI  - Haplotype distribution and molecular defects of PKU in Italy.

PMID- 1977955
TI  - The detection of abnormal metabolites in MCAD deficiency: a new method.

PMID- 1977957
TI  - Development and cancer: common themes?

PMID- 1977956
TI  - Advances in the molecular genetics of metachromatic leukodystrophy.
AB  - Metachromatic leukodystrophy is a lysosomal storage disorder caused by the
      deficiency of arylsulphatase A (EC 3.1.6.1). This results in the intralysosomal
      storage of cerebroside sulphate, which leads to a progressive demyelination of
      the nervous system. The patients usually die within a few years from the onset of
      symptoms. Clinically, there are different forms of the disease and the molecular
      basis for this heterogeneity is unknown. The gene for arylsulphatase A has
      recently been cloned and provides a necessary tool for the exact description of
      the molecular defects occurring in the different forms of metachromatic
      leukodystrophy. Metachromatic leukodystrophy can also be caused by the deficiency
      of an arylsulphatase A activator protein (sphingolipid activator protein B). The
      cDNA for the precursor of this protein has been isolated and a mutant cDNA of one
      patient has been analysed. A substantial arylsulphatase A deficiency can also
      occur in healthy individuals, a phenotype termed pseudodeficiency. Two concurrent
      mutations have been identified in this low arylsulphatase A activity allele. This
      permitted the development of a rapid assay which allows the detection of the
      pseudodeficiency allele. Bone marrow transplantation has been tried in several
      metachromatic leukodystrophy patients and there is evidence that this treatment
      might slow or even halt the progression of the disease. A final conclusion as to
      whether bone marrow transplantation is a suitable therapy for metachromatic
      leukodystrophy cannot be drawn yet.

PMID- 1977958
TI  - Deoxyribonucleic-binding homeobox proteins are augmented in human cancer.
AB  - Homeobox genes encode sequence-specific DNA-binding proteins that are involved in
      the regulation of gene expression during embryonic development. In this study, we
      examined the expression of homeobox proteins in human cancer. Antiserum was
      obtained against a synthetic peptide derived from the highly conserved 60 amino
      acid homeodomain. This peptide antiserum recognized a protein species of
      molecular weight 63,000 in immunoblots of nuclear extracts obtained from several
      tumor cell lines. The predominant molecular weight 63,000 nuclear protein
      recognized by the peptide antiserum was then isolated and used to elicit a rabbit
      antiserum. In immunostaining, both antisera reacted with the nuclei of cultured
      tumor cells. In tissue sections of human carcinoma, nuclear immunoreactivity was
      observed in the tumor cells in 40 of 42 cases examined. Adjacent normal
      epithelial tissue obtained from the same patients exhibited little
      immunoreactivity. Both the peptide antiserum and the polyclonal antiserum against
      the native protein immunoblotted a molecular weight 63,000 protein in nuclear
      extracts of tumor tissue, but not significantly in extracts of normal tissue. At
      the molecular level, the presence of the homeobox transcript in human carcinoma
      was documented by in situ hybridization and RNase protection mapping. These
      results demonstrate that human cancer is associated with the expression of
      homeobox proteins. Such homeobox proteins, as well as other regulatory proteins,
      could be involved in the initiation or maintenance of the malignant phenotype.

PMID- 1977959
TI  - Immunolocalization of heparan sulfate proteoglycans to the prion protein amyloid
      plaques of Gerstmann-Straussler syndrome, Creutzfeldt-Jakob disease and scrapie.
AB  - Previous histochemical studies have demonstrated highly sulfated
      glycosaminoglycans (GAGs) localized to the amyloid plaques in the brains of
      humans and animals with prion diseases (Snow et al., Acta Neuropathol 77:337,
      1989). However, the identity of the specific class of proteoglycan/GAG present
      was not known. The current investigation used immunocytochemical techniques to
      identify and localize heparan sulfate proteoglycans (HSPGs) in human cases of
      Gerstmann-Straussler syndrome and Creutzfeldt-Jakob disease, as well as in
      experimental scrapie of hamsters. Polyclonal and monoclonal antibodies to either
      the protein core or GAG moiety of the basement membrane-derived HSPG were
      utilized. The results demonstrate that both the protein core and the GAG chains
      of HSPGs are immunolocalized to the prion protein amyloid plaques in each of
      these diseases. HSPG immunostaining was also evident in these tissues in blood
      vessels, choroid plexus, myelinated axons, and in the cytoplasm of certain
      neuronal and astrocytic populations, particularly those in close proximity to the
      amyloid plaques. Additionally, in Creutzfeldt-Jakob disease and Gerstmann
      Straussler syndrome cerebellum, positive immunostaining for heparan sulfate GAGs
      was observed within the cell bodies of Purkinje cells. The specific accumulation
      of HSPGs in the amyloid deposits of both the prion diseases and Alzheimer's
      disease (Snow et al., Am J Pathol 133:456, 1988), suggests that a common
      mechanism involving HSPGs may occur in the pathogenesis of amyloidosis in each of
      these diseases.

PMID- 1977961
TI  - [The course of development of the International Orthopedic Association].

PMID- 1977962
TI  - [Assessment, reproducibility and sources of error in sonographic examination of
      the hip].
AB  - To the sonographic examination of the hip middle-category devices with real-time
      working and 5 MHz linear probing heads are necessary. Special laying and
      documentation is suggested to the rapid and easy execution and assessment of the
      examinations. If the examination is carried out in a standard plane the points of
      orientation characterising the acetabulum are represented unequivocally and
      clearly, the results gained can be reproduced and compared.

PMID- 1977960
TI  - Optimization of differential immunogold-silver and peroxidase labeling with
      maintenance of ultrastructure in brain sections before plastic embedding.
AB  - The limited success of immunogold labeling for pre-embedding immunocytochemistry
      of neuronal antigens is largely attributed to poor penetration of large (5-20 nm)
      colloidal gold particles. We examined the applicability of using silver
      intensification of 1 nm colloidal gold particles non-covalently bound to goat
      anti-rabbit immunoglobulin (1) for single labeling of a rabbit antiserum against
      the catecholamine synthesizing enzyme, tyrosine hydroxylase (TH), and (2) for
      immunogold localization of rabbit anti-TH simultaneously with immunoperoxidase
      labeling of a mouse monoclonal antibody against the opiate peptide, leucine
      enkephalin (LE). Vibratome sections were collected from acrolein fixed brains of
      adult rats. These sections were immunolabeled without use of freeze-thawing or
      other methods that enhance penetration, but damage ultrastructure. By light
      microscopy, incubations in the silver intensifier (Intense M, Janssen) for less
      than 10 min at room temperature resulted in a brownish-red reaction product for
      TH. This product was virtually indistinguishable from that seen using
      diaminobenzidine reaction for detection of peroxidase immunoreactivity. Longer
      incubations produced intense black silver deposits that were more clearly
      distinguishable from the brown immunoperoxidase labeling. However, by light
      microscopy, the gold particles seen by electron microscopy were most readily
      distinguished from peroxidase reaction product with shorter silver
      intensification periods. The smaller size of gold particles with shorter periods
      of silver intensification also facilitated evaluation of labeling with respect to
      subcellular organelles. Detection of the silver product did not appear to be
      appreciably changed by duration of post-fixation in osmium tetroxide. In dual
      labeled sections, perikarya and terminals exhibiting immunogold-silver labeling
      for TH were distinct from those containing immunoperoxidase labeling for LE.
      These results (1) define the conditions needed for optimal immunogold-silver
      labeling of antigens while maintaining the ultrastructural morphology in brain,
      and (2) establish the necessity for controlled silver intensification for light
      or electron microscopic differentiation of immunogold-silver and peroxidase
      reaction products and for optimal subcellular resolution.

PMID- 1977963
TI  - [Reoperations in the management of clubfoot].
AB  - The results of 118 operations for club-foot are assessed, of these 57 were
      reoperations. It is stated that the relapse is most often the consequence of the
      insufficient primary operation and the relapse and the residual deformity are the
      more serious the more insufficient was the primary operation. The severity of the
      deformation is defined first of all by the position of the calcaneus. In milder
      cases the soft tissue operation only may be successful, in the more severe cases
      bony operation (Evans' operation in this series of the authors) has also to be
      performed. After their own primary operations reoperation was in 24 per cent
      necessary. The number of the bony operations was half of the soft tissue
      operations. The second and rarer case of the relapses was that the foot proved to
      be even originally rigid, not redressable, "rebel". First of all in these cases
      may multiple reoperations be necessary and the transposition of the anterior
      tibial muscle is also useful. The club-foot with a major dominant adduction
      deformity of the tarsometatarsal joint is thought to be a separate entity and it
      is corrected with tarsometatarsal capsulotomies or serial metatarsal osteotomies.

PMID- 1977964
TI  - [Finger replantation].
AB  - Authors performed from 1979 to 1989 on 89 fingers of 65 patients replantation or
      revascularization operations after total or partial amputations. The procedure
      was unsuccessful in 16 cases. The operation was successful in 82 per cent and
      this corresponds to the literary data. It is stressed that the operative result
      depends not from the survival of the finger but from the functional end result.

PMID- 1977965
TI  - [Results of surgical management of Bennett fractures].
AB  - Authors examined in a 15-year material of the Department of Traumatology, Clinic
      of Surgery of the Pecs University of Medicine the late results of Bennett's
      fracture, treated surgically. In the treatment of 51 patients they came to the
      conclusion that the reduction of the fracture with anatomical exactness and the
      early functional treatment improved the results considerably.

PMID- 1977966
TI  - [The role of an external mini-fixator in the management of infected injuries of
      the hand].
AB  - Authors use since 1982 the mini fixateur externe in the treatment of the severe
      infected injuries of the hand. The stable, external fixation resulted in all the
      31 patients, treated unsuccessfully with other methods, in healing.

PMID- 1977967
TI  - [Diagnosis and therapy of injuries of the lamina fibrocartilaginea of the hand
      (palmar plate)].
AB  - Authors studied a frequent injury of the finger joints. The anatomy, the
      mechanism of the injuries, the diagnostic possibilities of the lamina
      fibrocartilaginea ("palmar plate") and of the palmar ligaments of the joints are
      described. In the diagnosis a special significance is attached to the stressed
      and tangential X-ray pictures. They take the part of the conservative treatment
      of the injury. In cases of dislocations, that cannot be reduced, of open "palmar
      plate" injuries and of major hyperextension and dislocations of the broken bone
      scale, operative treatment is thought necessary. In the treatment of the injuries
      of the "palmar plate" of the PIP joint they use the so called rein method, that
      keeps the palmar cartilaginous joint capsule, torn at the injury, on its original
      place, it enables however the active joint movements, the gymnastics and hinders
      this way the development of the joint contracture.

PMID- 1977968
TI  - [Direct measurement of the pulling force affecting the flexor tendons of the
      hand].
AB  - A thought, returning again and again in hand surgery, is the immediate
      introduction of active motion therapy after the reconstructive operations of the
      flexor tendons. To the active motion an adequately strong tendon suture, to the
      definition of "adequately strong tendon suture" however the measurement of the
      pulling force, acting actually on the flexor tendons is necessary. Authors
      attempted to measure this pulling force during flexor tendon operations on
      cadaver's hand. On the basis of their measurements the maximal pulling force,
      that can be expected during postoperative active movement exercises with adequate
      circumspection, can be estimated as two kiloponds.

PMID- 1977969
TI  - [Management of open, potentially infected hand injuries with bone defect by
      delayed early bone substitution].
AB  - Authors make an analogy between the principles of treatment of the fresh,
      potentially infected injuries with bone and soft tissue defects and of the
      already developed manifest infection of the hand. The principles of treatment are
      essentially the same. First of all the fixateur externe and the antibiotics
      containing globules are suggested for the sanation and prevention of the disease
      equally. Attention is called to the fact, that better results can be expected
      from the prophylaxis than from the attempts to make the process reversible. The
      beneficial synergism of the extrafocal fixation and the intrafocally acting
      antibiotics will help. One of the secrets of the good late functional results is
      the early restitution of the architecture of the bones of the hand. For this, the
      authors suggest the most modern replacement of bone in the form of primary
      delayed cancellous bone plasty, performed within two weeks.

PMID- 1977970
TI  - [Preservation of the upper extremity by using an external fixator after deep burn
      injury].
AB  - Authors report on conservation of the upper extremity endangered by severe burn
      of the shoulder region with the use of fixateur externe. No publication
      describing the use of fixateur externe in burned patients for similar aim was
      found in the literature.

PMID- 1977971
TI  - [Bilateral fractures of the proximal end of the radius].
AB  - Authors describe in connection with two cases of their own the vulnerability of
      the elbow joint originating from the physiological valgus position of this joint,
      i.e. the effect of the so-called "valgus stress". In the available literature no
      description of bilateral synchronous fracture of the radial head was found. They
      think, because of the bilateral injury, the correct operative therapy with the
      aim of reaching whole function, the stable osteosynthesis promising good result
      even in the fracture of the radial neck with major dislocation allowing also an
      early functional treatment, important.

PMID- 1977972
TI  - Histamine lipolysis I: changes in the free fatty acid levels of dog plasma after
      intravenous infusion of histamine.
AB  - The effects of histamine (Hi) and related compounds on free fatty acid (FFA)
      levels and % changes in FFA composition of dog plasma were studied after
      intravenous infusion. Hi at doses of 2-10 micrograms/kg while affecting no
      changes in the cardiovascular system elicited a dose-related increase in FFA
      levels in plasma, as did epinephrine. Though all of the FFA concentrations in
      plasma were increased by Hi infusion, % change of each FFA in the composition did
      not correspond to that of plasma concentration; % increases in palmitoleic acid,
      linolenic acid and linoleic acid were remarkable, while stearic acid (18:0) was
      lowest. The increase in arachidonic acid was not marked, but a dose-related
      increase was observed after Hi infusion. The H2-agonist 4-methylHi produced an
      increase in FFA levels, whereas the H1-agonist 2-methylHi was not effective. 4
      MethylHi increased all of the plasma FFA levels and the relative changes were
      similar to those caused by Hi. The effect induced by Hi was blocked by the H2
      antagonists cimetidine and ranitidine. Pretreatment with aminophylline
      potentiated the Hi effect, indicating that Hi lipolysis may be intimately related
      to cyclic AMP.

PMID- 1977973
TI  - [Serum cholesterol, serum triglyceride, alcohol, myocardial infarction and death
      (1): Increased serum GT is strongly related to alcohol-induced diseases].

PMID- 1977974
TI  - [Serum cholesterol, serum triglyceride, alcohol, myocardial infarction and death
      (2): necessary to pay attention to serum GT in assessment of risks of myocardial
      infarction and death].

PMID- 1977975
TI  - [Nephropathia epidemica--a current disease in Norrland].

PMID- 1977976
TI  - [Monoamine research--a productive field of particular importance in
      neuroscience].
AB  - Modern monoamine research had its origin in work done in the 1950s and 1960s to
      elucidate the modes of action of the major groups of psychotropic drugs, since
      when it has played a spearhead role in neuroscience. For example, it has
      contributed much to the introduction of the chemical neurotransmission concept in
      CNS-research. We are now about to reap the harvest of more than three decades of
      intensive and successful basic research, in the form of more efficacious and
      safer drugs for the treatment of certain important mental and neurological
      disorders, and the formulation of research strategies focused on prophylaxis. The
      paper reviews this development.

PMID- 1977977
TI  - Independent genetic determinants of pancreatic and pulmonary status in cystic
      fibrosis.
AB  - The concordance of pancreatic and pulmonary status among siblings with cystic
      fibrosis, the cystic fibrosis genotype, and non-genetic factors were analysed in
      adult patients with cystic fibrosis. Genetic factors were more important than non
      genetic factors in affecting the severity of pancreatic and lung disease. The
      genetic factors were independent of each other and did not invariably cosegregate
      with specific mutations at the cystic fibrosis locus.

PMID- 1977978
TI  - Test for recovery from hypothyroidism during thyroxine therapy in Hashimoto's
      thyroiditis.
AB  - Hypothyroid patients with Hashimoto's thyroiditis usually receive lifelong
      thyroxine therapy. Some are known to recover thyroid function, but identification
      of these patients during continued thyroxine therapy has been impossible. 92
      patients with hypothyroidism after Hashimoto's thyroiditis and 70 normal controls
      were studied. All controls but not patient before thyroxine was started had a
      normal thyroid response to thyroid stimulating hormone (TSH), circulating
      concentrations of which were increased by administration of 500 micrograms
      thyrotropin releasing hormone (TRH). During treatment with thyroxine, 22 patients
      recovered thyroid responsiveness to TSH, and when treatment was stopped these
      patients have remained euthyroid for 1-8 years, whereas all 70 who did not
      recover thyroid TSH responsiveness became hypothyroid within 3 months. Over 20%
      of patients with hypothyroidism after Hashimoto's thyroiditis may recover
      satisfactory thyroid function, and can be identified during thyroxine treatment
      by their thyroid response to TSH in a TRH test.

PMID- 1977979
TI  - Coagulation factor abnormalities as possible thrombotic risk factors after Fontan
      operations.
AB  - Severe thromboembolism occurred in 3 of 37 patients who had undergone Fontan-type
      operations for correction of congenital heart defects several months to years
      after the operation. The patients were screened for coagulation factor
      abnormalities to find out whether known prothrombotic risk factors could explain
      the high frequency of thromboembolism. 63 abnormalities were found in 24 of the
      37 patients. The commonest and most pronounced abnormality was deficiency of
      protein C, a known risk factor. Concentrations of antithrombin III and factors II
      and X were significantly lower in protein-C-deficient patients than in those with
      normal protein C concentrations. These findings suggest that the high thrombotic
      risk in these patients is caused or at least associated with an imbalance between
      procoagulant and anticoagulant factors.

PMID- 1977980
TI  - Effect of short-term intermittent antibiotic treatment on growth of Burmese
      (Myanmar) village children.
AB  - To test the hypothesis that subclinical enteric infection (such as bacterial
      overgrowth), rice malabsorption, and growth faltering are causally linked, a
      field trial of low-dose, short-term, intermittent antibiotic treatment was
      carried out in 142 hydrogen-producing (by lactulose breath hydrogen test) Burmese
      village children aged 6-59 months. The children were randomly allocated treatment
      with metronidazole (20 mg/kg or 5 mg/kg daily), amoxycillin (25 mg/kg daily), or
      placebo given 1 week per month for 6 months. A cooked rice meal breath hydrogen
      test was done to classify the children as rice absorbers (RA) or rice
      malabsorbers (RM) before treatment and monthly on the day before each cycle of
      treatment. There were no differences between the treatment groups, so they were
      considered together. Factorial analysis showed that antibiotic treatment did not
      significantly affect the proportion of RM children. The only significant
      difference between antibiotic-treated and placebo-treated children's growth was
      in the subgroup of RM children aged 36-47 months; the antibiotic-treated children
      had significantly greater linear growth. In other age groups antibiotic treatment
      had no effect on growth.

PMID- 1977981
TI  - Person-to-person transmission of Pseudomonas cepacia between patients with cystic
      fibrosis.
AB  - Ribotyping, a method of strain identification based on analysis of bacterial
      genomic restriction fragment length polymorphisms, was used to investigate the
      acquisition of Pseudomonas cepacia by a patient with cystic fibrosis. Analysis of
      isolates recovered from the index patient and his contacts showed person-to
      person transmission of this opportunist organism. This documentation of the
      transmission of P cepacia from one cystic fibrosis patient to another suggests
      that measures to limit the acquisition of the pathogen by patients with cystic
      fibrosis may be worth while.

PMID- 1977982
TI  - Hypothesis revisited: toothpaste and the cause of Crohn's disease.

PMID- 1977984
TI  - Chirality.

PMID- 1977983
TI  - Polycystic ovaries--disorder or sign?

PMID- 1977985
TI  - Bridging the gap.

PMID- 1977986
TI  - Occupational infection among anaesthetists.

PMID- 1977987
TI  - Prone, hot, and dead.

PMID- 1977988
TI  - Effect of delivery room routines on success of first breast-feed.
AB  - 72 infants delivered normally were observed for 2 h after birth. In the
      separation group (n = 34), the infant was placed on the mother's abdomen
      immediately after birth but removed after about 20 min for measuring and
      dressing. In the contact group (n = 38) contact between mother and infant was
      uninterrupted for at least 1 h. After about 20 min the infants began to make
      crawling movements towards the breast; the rooting reflex soon came into play,
      and at an average of 50 min after birth most of the infants were sucking at the
      breast. More infants in the contact group than in the separation group showed the
      correct sucking technique (24/38 vs 7/34). 40 (56%) of the 72 mothers had
      received pethidine during labour; the infants were also sedated and most of them
      (25/40) did not suck at all. It is suggested that contact between mother and
      infant should be uninterrupted during the first hour after birth or until the
      first breast-feed has been accomplished, and that use of drugs such as pethidine
      should be restricted.

PMID- 1977989
TI  - Risk factors for transmission of hepatitis B virus to Gambian children.
AB  - Risk factors for hepatitis B virus transmission were examined in 973 Gambian
      children aged 6 months to 5 years. 33% had evidence of infection with hepatitis B
      virus and a third of these were carriers. A significant association was found
      between infection and tropical ulcer scars, and between e antigenaemia and the
      presence of bedbugs in each child's bed. There was no association between
      infection and traditional scarring, circumcision, or injections. Skin disease and
      arthropods are the two most likely modes of transmission of hepatitis B virus
      between children in West Africa.

PMID- 1977991
TI  - Pathogenic Escherichia coli, Yersinia enterocolitica, and Vibrio
      parahaemolyticus.

PMID- 1977990
TI  - Buruli ulcer in Benin.
AB  - In a study of 28 patients with Mycobacterium ulcerans infection (Buruli ulcer) in
      Oinhi, Benin, it became clear that the disease can regress as well as progress,
      and that patients can have lesions of different stages simultaneously. A system
      of disease staging was introduced (I = subcutaneous nodule; II = cellulitis; III
      = ulceration; IV = scar formation). Research to find an effective treatment for
      this crippling disease is urgently needed.

PMID- 1977992
TI  - Which heart valves should we use?

PMID- 1977993
TI  - Withholding of life-saving treatment.

PMID- 1977994
TI  - Global health care for HIV disease.

PMID- 1977995
TI  - Drug abusers in prison.

PMID- 1977996
TI  - Management of epilepsy.

PMID- 1977997
TI  - Management of epilepsy.

PMID- 1977998
TI  - Identification of spores of Enterocytozoon bieneusi in stool and duodenal fluid
      from AIDS patients.

PMID- 1977999
TI  - HIV-associated haemophagocytic syndrome.

PMID- 1978000
TI  - Hypoglycaemia and cerebral malaria.

PMID- 1978001
TI  - Outbreak of acute toxic psychosis attributed to Mucuna pruriens.

PMID- 1978002
TI  - Community-based approach to pneumonia.

PMID- 1978003
TI  - Depot clopenthixol.

PMID- 1978004
TI  - Therapy-related myeloid leukaemia.

PMID- 1978005
TI  - Chocolate and the auto-brewery syndrome.

PMID- 1978006
TI  - Unusual presentation of fragile X syndrome.

PMID- 1978007
TI  - Fetal neural graft survival.

PMID- 1978008
TI  - Effect of mite allergen on permeability of bronchial mucosa.

PMID- 1978009
TI  - Extracorporeal membrane oxygenation.

PMID- 1978010
TI  - Nuchal fluid accumulation in trisomy-21 detected by vaginosonography in first
      trimester.

PMID- 1978011
TI  - Tolerance and the fetal graft.

PMID- 1978012
TI  - Bone density screening for osteoporosis.

PMID- 1978013
TI  - Paroxysmal dystonic reflex choreoathetosis after minor closed head injury.

PMID- 1978014
TI  - Borrelia burgdorferi and tropical spastic paraparesis.

PMID- 1978015
TI  - Gemfibrozil-induced impotence.

PMID- 1978016
TI  - HTLV-I infection in Iraq.

PMID- 1978017
TI  - Rhabdomyolysis and a "greenhouse effect".

PMID- 1978018
TI  - Radiation exposure and cardiac catheterisation.

PMID- 1978019
TI  - Myocardial infarction in a blood donor after administration of desmopressin.

PMID- 1978020
TI  - Convulsions in epileptic women after administration of prostaglandin E2
      derivative.

PMID- 1978021
TI  - 21-year follow-up of myokymia with impaired muscle relaxation.

PMID- 1978022
TI  - Photodynamic therapy of localised prostatic cancer.

PMID- 1978023
TI  - Darwin's illness.

PMID- 1978024
TI  - Hypersecretion of luteinising hormone, infertility, and miscarriage.
AB  - The relation between prepregnancy follicular-phase serum luteinising hormone (LH)
      concentrations and outcome of pregnancy was investigated prospectively in 193
      women with regular spontaneous menstrual cycles. The group included 26
      nulliparous and 167 multiparous women with various obstetric histories. Of the
      147 women with LH concentrations of less than 10 IU/l (normal LH group) 130 (88%)
      conceived, whereas only 31 (67%) of the 46 women with LH values of 10 IU/l or
      more (high LH group) did so. In the high LH group, 20 (65%) of the pregnancies
      ended in miscarriage, whereas only 15 (12%) of pregnancies in the normal LH group
      did so. The adverse effect of a high prepregnancy LH concentration on fertility
      and outcome of pregnancy was seen in primigravidae, women with previously
      successful pregnancies, and women with a history of recurrent miscarriage. These
      data indicate an important role for hypersecretion of LH before conception in
      miscarriage. This finding offers the possibility of a simple predictive test for
      women before pregnancy, and could also be used to identify patients with an
      endocrine abnormality that can be remedied.

PMID- 1978025
TI  - Serum endothelin-1 concentrations and cold provocation in primary Raynaud's
      phenomenon.
AB  - To determine whether the vasoconstriction in Raynaud's phenomenon is associated
      with raised concentrations of the endothelium-derived vasoconstrictor endothelin
      (ET-1), responses to cold pressor testing were examined in 7 subjects with
      primary Raynaud's phenomenon and in 7 control subjects. Baseline serum ET-1
      levels (pg/ml), as measured by radioimmunoassay, were three times higher in
      Raynaud's subjects (5.3 [SEM 1.7] pg/ml) than in controls (1.7 [0.3]). With
      progressive local cooling digital arterial pulsatility, as measured by
      plethysmography, fell earlier and to a greater extent in Raynaud's subjects than
      in controls, with a half-maximum decrement in pulsatility occurring at 27 [2.6]
      degrees C and 18 [0.5] degrees C, respectively. Temperature reduction sufficient
      to cause loss of pulsatility in the Raynaud's subjects produced increases in ET-1
      concentrations in both groups that were greater in Raynaud's (10.3 [4.4] pg/ml)
      than in control subjects (2.7 [0.9] pg/ml). Serum ET-1 in the contralateral arm
      rose in parallel to but to a lesser extent than that in the cold-challenged arm.
      Increases in ET-1 concentrations were temporally related to loss of pulsatility
      but followed the onset of symptoms. Thus the increased basal and stimulated serum
      endothelin concentrations in Raynaud's disease are associated with the enhanced,
      prolonged vasospasm of this disorder.

PMID- 1978027
TI  - Malignant transformation of adenomatous hyperplasia to hepatocellular carcinoma.
AB  - To clarify the course of adenomatous hyperplasia (AH) of the liver, 17 patients
      with 20 biopsy-proven AH nodules were followed clinically for 1-5 years. At the
      initial biopsy the mean nodular diameter was 10 (SD 4) mm and the relative
      cellularity [( mean cellularity of AH divided by mean parenchymal cellularity] x
      100) 141 (27). The criteria for diagnosis of malignant transformation of AH were
      both a doubling of nodular volume and changes on imaging. Between 6 and 50 months
      after biopsy, 9 of the 18 nodules which could still be accurately identified met
      the criteria for transformation; histological proof of hepatocellular carcinoma
      (HCC) was obtained later for 7 of these 9 nodules. The product of diameter and
      cellularity (transformation index) was the strongest predictor of the time to
      transformation. 9 AH nodules did not undergo transformation--7 did not meet one
      or both criteria and 2 became undetectable by imaging. Because of the high risk
      of malignant transformation, it can be concluded that AH is an absolute precursor
      of HCC. It should therefore be treated as a potential malignant disorder.

PMID- 1978026
TI  - Clearance of Rh D-positive red cells with monoclonal anti-D.
AB  - Two human monoclonal antibodies, one IgG3 and one IgG1, with anti-Rh D
      specificity, were tested for their ability to clear red cells. Samples of red
      cells from 12 D-positive subjects were sensitised in vitro with various amounts
      of antibody, the number of antibody molecules bound to the cells was estimated,
      and the cells were reinjected into the donor's circulation. Both antibodies
      mediated clearance but substantially fewer IgG3 than IgG1 antibody molecules were
      required to produce a given rate of clearance. The IgG3 antibody was slightly
      more effective than polyclonal anti-D, as judged by comparison with previously
      published results. Since there is believed to be an association between the rate
      of red cell clearance by anti-D and the ability of the antibody to suppress D
      immunisation, the IgG3 monoclonal antibody may prove suitable for the
      immunoprophylaxis of Rh D haemolytic disease.

PMID- 1978028
TI  - Type-specific antigens for serological discrimination of HTLV-I and HTLV-II
      infection.
AB  - 55 HTLV-I (human T-cell lymphotropic virus) and 45 HTLV-II carriers, confirmed by
      HTLV-type specific polymerase chain reaction (PCR), were distinguished by western
      blot assays with recombinant HTLV I or II envelope glycoproteins. Recombinant
      protein (RP) B1 contains aminoacids 166-201 from HTLV-I exterior glycoprotein
      gp46 and was reactive with HTLV-I samples only. RP-IIB, which contains aminoacids
      96-235 from HTLV-II exterior glycoprotein gp52, was reactive with all HTLV-II
      samples. 39 patients (86.6%) had high reactivity by densitometry. Of 55 HTLV-I
      samples, 35 (65.5%) had antibody reactivity to RP-IIB, but only 1 (1.8%) had high
      reactivity by densitometry. RP B1 and IIB western blot assays may replace the PCR
      test in diagnosis of HTLV infection.

PMID- 1978029
TI  - Who's for tennis?

PMID- 1978030
TI  - The A to F of viral hepatitis.

PMID- 1978031
TI  - Quality assurance and dialysis services.

PMID- 1978032
TI  - HTLV-I--a screen too many?

PMID- 1978033
TI  - Effect of exposure of miners to aluminium powder.
AB  - 'McIntyre Powder' (finely ground aluminium and aluminium oxide) was used as a
      prophylactic agent against silicotic lung disease between 1944 and 1979 in mines
      in northern Ontario. To find out whether the practice produced neurotoxic effects
      a morbidity prevalence study was conducted between 1988 and 1989. There were no
      significant differences between exposed and non-exposed miners in reported
      diagnoses of neurological disorder; however, exposed miners performed less well
      than did unexposed workers on cognitive state examinations; also, the proportion
      of men with scores in the impaired range was greater in the exposed than non
      exposed group. Likelihood of scores in the impaired range increased with duration
      of exposure. The findings are consistent with putative neurotoxicity of chronic
      aluminium exposure.

PMID- 1978034
TI  - Impact of active immunisation against enteritis necroticans in Papua New Guinea.
AB  - Enteritis necroticans, known locally as pigbel, has been a major cause of illness
      and death among children in the highlands of Papua New Guinea. After a successful
      trial of active immunisation against the beta toxin of the causative organism,
      Clostridium perfringens type C, immunisation of children was begun in 1980. The
      effects of the immunisation programme on pigbel admissions in 3 of the 5 major
      highland hospitals were assessed. In each of the centres studied the proportion
      of admissions due to enteritis necroticans dropped significantly after
      immunisation was introduced (p less than 0.001) and hospital admissions for
      pigbel in 1984-86, when immunisation was well established, were less than one
      fifth of previous figures.

PMID- 1978035
TI  - Changing epidemiology of group A streptococcal infection in the USA.
AB  - To see whether changes in the epidemiology of group A streptococcal disease in
      the USA have been accompanied by a corresponding change in serotype distribution,
      epidemiological and M-typing and T-typing data for 5193 strains sent to the
      Centers for Disease Control, Atlanta, between 1972 and 1988 were analysed. The
      proportions of M-types 1, 3, and 18 increased significantly during the study
      period. These M-types were more likely to be invasive, to cause fatal infection,
      and to occur in a cluster of infections than were other types. By contrast, the
      proportions of M-types 4 and 12 decreased; they were less invasive and were less
      likely to be found in clusters than were other types. These data suggest that
      changes in the epidemiology of group A streptococcal disease may be related to
      changes in the distribution of M-types causing infection.

PMID- 1978036
TI  - Foodborne listeriosis.

PMID- 1978037
TI  - Features of "near-death experience" in relation to whether or not patients were
      near death.
AB  - The medical records of 58 patients, most of whom believed they were near death
      during an illness or after an injury and all of whom later remembered unusual
      experiences occurring at the time, were examined. 28 patients were judged to have
      been so close to death that they would have died without medical intervention;
      the other 30 patients were not in danger of dying although most of them thought
      they were. Patients of both groups reported closely similar experiences but
      patients who really were close to death were more likely than those who were not
      to report an enhanced perception of light and enhanced cognitive powers. The
      claim of enhancement of cognitive functions despite the likelihood that brain
      function had probably become disturbed and possibly diminished, deserves further
      investigation.

PMID- 1978038
TI  - Tummy tucks and taxes.

PMID- 1978039
TI  - Transsexuals and the law.

PMID- 1978040
TI  - Bristol Cancer Help Centre.

PMID- 1978041
TI  - PET and [11C]methionine in assessment of response in non-Hodgkin lymphoma.

PMID- 1978042
TI  - ACE inhibitors and tissue binding.

PMID- 1978043
TI  - Oral treatment of late borreliosis with roxithromycin plus co-trimoxazole.

PMID- 1978044
TI  - Multiple sclerosis in early childhood.

PMID- 1978045
TI  - Taste disturbance with acetazolamide.

PMID- 1978046
TI  - Recurrent miscarriage.

PMID- 1978047
TI  - Registration of births at less than 22 weeks' gestation.

PMID- 1978048
TI  - Yoga breathing exercises and bronchial asthma.

PMID- 1978049
TI  - Continuous arteriovenous haemofiltration in hyperammonaemia of newborn babies.

PMID- 1978050
TI  - Ciprofloxacin and Clostridium difficile infection.

PMID- 1978051
TI  - Is anti-HCV blood donor screening useful?

PMID- 1978052
TI  - Emergency health kits.

PMID- 1978053
TI  - High mortality among recipients of bought living-unrelated donor kidneys.

PMID- 1978054
TI  - Services for migrant drug abusers.

PMID- 1978055
TI  - Ethical committees?

PMID- 1978056
TI  - Assisted death.

PMID- 1978057
TI  - Risk of burns during rapid-rate magnetic stimulation in presence of electrodes.

PMID- 1978058
TI  - Simvastatin and ursodeoxycholic acid for rapid gallstone dissolution.

PMID- 1978059
TI  - Bedside blood compatibility testing.

PMID- 1978060
TI  - In-vitro production of cytokines in blood.

PMID- 1978061
TI  - HIV and travel, no rationale for restrictions.

PMID- 1978062
TI  - Construction projects and spread of HIV.

PMID- 1978063
TI  - Re-use of 'HIV-check' in developing countries.

PMID- 1978064
TI  - Routine screening for Corynebacterium diphtheriae.

PMID- 1978065
TI  - Sudden infant death syndrome in China.

PMID- 1978066
TI  - Electrocardiogram changes in localised myocardial injury by bullet.

PMID- 1978067
TI  - Self-experimentation.

PMID- 1978068
TI  - TNF concentration in fatal cerebral, non-fatal cerebral, and uncomplicated
      Plasmodium falciparum malaria.
AB  - Plasma levels of tumour necrosis factor (TNF) were significantly higher in 178
      Gambian children with uncomplicated malaria due to Plasmodium falciparum than in
      178 children with other illnesses. 110 children with cerebral malaria were
      studied shortly after admission to hospital; 28 subsequently died. Compared with
      the children with uncomplicated malaria, mean plasma TNF levels were twice as
      high in cerebral malaria survivors and ten times as high in the fatal cases.
      Although high TNF levels were associated with high parasitaemia and with
      hypoglycaemia, they predicted fatal outcome in cerebral malaria independently of
      parasitaemia and glucose concentrations. Concentrations of interleukin-1 alpha,
      but not interferon gamma, were also related to the severity of malaria. We
      conclude that increased TNF production is a normal host response to P falciparum
      infection, but that excessive levels of production may predispose to cerebral
      malaria and a fatal outcome.

PMID- 1978069
TI  - Randomised, double-blind, placebo-controlled trial of nimodipine in acute stroke.
      Trust Study Group.
AB  - The value of oral nimodipine 120 mg per day for acute stroke was assessed in a
      randomised, double-blind, placebo-controlled multicentre study of 1215 patients.
      The primary end-point was independence after 6 months, defined as a score of 60
      or more on an activities of daily living (ADL) scale, the Barthel index. Patients
      were entered into the trial if they were aged over 40, became hemiparetic in the
      previous 48 h, were conscious, were able to swallow, and had been living
      independently before the stroke. At 6 months, 55% of the nimodipine group and 58%
      of the placebo group were independent, the odds ratio for independence on
      nimodipine being 0.88 (95% confidence limits 0.70-1.10). For mortality the odds
      ratio with nimodipine was 1.22 (95% confidence limits 0.95-1.57). ADL and
      neurological scores also suggested delayed recovery in the nimodipine group at 3
      weeks. The results do not support the case for oral nimodipine therapy 120 mg per
      day starting within 48 h of the stroke, for patients with acute stroke.

PMID- 1978070
TI  - Value of antigen detection in predicting invasive pulmonary aspergillosis.
AB  - Two ELISAs were used to detect serum and urinary aspergillus antigen in 121
      patients who were profoundly neutropenic after leukaemia therapy or bone marrow
      transplantation. The presence of antigen correctly predicted development of
      invasive pulmonary aspergillosis (IPA) in 16 patients. In 2 other cases antigen
      appeared after the clinical diagnosis had been made, while in only 1 case was
      antigen not detected. In 11 of 13 episodes of clinically suspected fungal
      infection antigen was detected before clinical diagnosis was made. By contrast,
      antigen was detected in only 1 of 90 patients who had no evidence of IPA. Both
      ELISAs gave positive and negative predictive values for IPA of greater than 95%,
      demonstrating the value of antigen detection in early diagnosis of aspergillus
      infection and the assay's ability to predict subsequent development of IPA. We
      conclude that neutropenic patients should be screened for aspergillus antigen,
      and propose that initial detection of fungal antigen justifies commencement of
      empirical antifungal therapy. Such an approach should improve the survival of
      patients who are at risk of developing this usually fatal infection.

PMID- 1978071
TI  - Antibody profile of early HTLV-I infection.
AB  - To define the antibody profile of early seroconversion in infection with human T
      cell lymphotropic virus type I (HTLV-I), consecutive serum samples from 10
      subjects presumed to have seroconverted on the basis of the particle
      agglutination test were studied by three enzyme immunoassays and two confirmatory
      tests (radioimmunoprecipitation and western blot). 3 samples positive and 1
      sample indeterminate in the confirmatory tests were reactive in one enzyme
      immunoassay, which used recombinant envelope antigen, but not in the other two
      enzyme immunoassays. 2 of 38 particle-agglutination-negative samples had a
      prozone effect. The confirmatory tests identified 8 seroconverters (7 women, 1
      man); their serum samples were used to study the antibody reactivity by western
      blot assays to HTLV-I specific antigens (three recombinant proteins spanning the
      N-terminal, middle, and C-terminal env glycoprotein gp46; a recombinant
      transmembrane protein gp21; a recombinant tax protein; and three gag proteins
      [p28, p24, and p19]). All 8 seroconverters had antibody reactivities to the C
      terminal region (aminoacid residues 229-308) of gp46 and to gag p19 and p24 when
      their seroconversion was detected.

PMID- 1978072
TI  - Preliminary report: the antegrade continence enema.
AB  - The principles of antegrade colonic washout and the Mitrofanoff non-refluxing
      catheterisable channel were combined to produce a continent catheterisable
      colonic stoma. The intention was that antegrade washouts delivered by this route
      would produce complete colonic emptying and thereby prevent soiling. The
      procedure has been successfully carried out in five patients with intractable
      faecal incontinence.

PMID- 1978073
TI  - Neurohumoral responses to thermal injury.

PMID- 1978074
TI  - Now we understand antipsychotics?

PMID- 1978075
TI  - Alcohol and violence.

PMID- 1978076
TI  - Cystic fibrosis: towards the ultimate therapy, slowly.

PMID- 1978077
TI  - Clinical ultrasound in developing countries.

PMID- 1978078
TI  - Brevity in the Lancet.

PMID- 1978079
TI  - On-line cartography in Oxford.

PMID- 1978080
TI  - The fifth freedom revisited: I, Background and existing programmes.

PMID- 1978081
TI  - Foodborne salmonellosis.

PMID- 1978082
TI  - Increased cholecystectomy rates in Saudi Arabia.
AB  - Gallstones have become increasingly prevalent in Saudi Arabia, where
      cholecystectomy is now one of the commonest major abdominal operations. 2854
      people underwent cholecystectomy in the 14 hospitals of the country's Eastern
      Province in the years 1977 to 1986. During this period the overall frequency of
      cholecystectomy increased by 978%, a finding not explained by the 67% increase in
      population or the 87% increase in other operations. Simultaneously, the average
      daily individual consumption of total calories, fat, and sugar increased by 81%,
      197%, and 164%, respectively, and consumption of high-fibre grain fell by 75%.
      This striking increase in the frequency of cholecystectomy, which presumably
      reflects the incidence of gallstones, cannot be explained by demographic changes
      and seems more closely linked to the concomitant changes in dietary habits.

PMID- 1978083
TI  - Race or class versus race and class: mortality differentials in the United
      States.

PMID- 1978084
TI  - Creative expression and chronic pain.

PMID- 1978085
TI  - Cutaneous malignancy in males treated with photochemotherapy.

PMID- 1978086
TI  - Evolution of primary empty sella syndrome.

PMID- 1978087
TI  - Lack of inhibitor to monoclonal-antibody purified factor VIII concentrate.

PMID- 1978088
TI  - No role for 65 kD heat-shock protein in diabetes.

PMID- 1978089
TI  - Placental transfer of mercury from amalgam.

PMID- 1978090
TI  - Kaposi's sarcoma associated with captopril.

PMID- 1978091
TI  - Low-dose aspirin and heparin in unstable coronary artery disease.

PMID- 1978092
TI  - Reporting compliance in clinical trials.

PMID- 1978093
TI  - Endothelial dysfunction in vascular disease.

PMID- 1978094
TI  - Testicular cancer, dimethylformamide, and leather tanneries.

PMID- 1978095
TI  - Chinese herbs for eczema.

PMID- 1978096
TI  - Colonic fermentation, luminal substrate, and intoxication.

PMID- 1978097
TI  - Itraconazole and anti-tuberculosis drugs.

PMID- 1978098
TI  - Latent herpesvirus-6 in salivary and bronchial glands.

PMID- 1978099
TI  - Zidovudine-related myopathy.

PMID- 1978100
TI  - Asymptomatic disseminated Pneumocystis carinii infection detected by
      ophthalmoscopy.

PMID- 1978101
TI  - Pseudomonas pseudomallei and sudden unexplained death in Thai construction
      workers.

PMID- 1978102
TI  - Salbutamol nebuliser and precipitation of critical cardiac ischaemia.

PMID- 1978103
TI  - Intestinal obstruction in babies exposed in utero to methylene blue.

PMID- 1978104
TI  - Cancer and electromagnetic fields.

PMID- 1978105
TI  - Ayur-Vedic medicine.

PMID- 1978106
TI  - Cervical cancer in New Zealand.

PMID- 1978107
TI  - Ethics and clinical research.

PMID- 1978109
TI  - Trends in cancer mortality.

PMID- 1978108
TI  - Cross-resistance between mefloquine and halofantrine.

PMID- 1978110
TI  - Corticosteroid pharmacokinetics in asthma.

PMID- 1978111
TI  - P300 as a predictor of recovery from coma.

PMID- 1978112
TI  - Pneumococcal bacteraemia in two immunocompetent adults with otitis media and
      bronchitis.

PMID- 1978113
TI  - National General Practice Study of Epilepsy: newly diagnosed epileptic seizures
      in a general population.
AB  - The National General Practice Study of Epilepsy is a prospective population-based
      cohort study of 1195 patients with newly diagnosed or suspected epileptic
      seizures. At the time of initial classification (6 months after notification),
      104 patients were excluded. Of the remaining 1091 patients, 220 (20% [95%
      confidence interval 18-23%]) had febrile seizures, 564 (52% [49-55%]) definite
      epileptic seizures, and 228 (21% [19-23%]) possible epilepsy. In the definite
      epilepsy group the proportions of males and females were similar, 25% (21-28%)
      were younger than 15 years and 24% (21-28%) were 60 years or older. The definite
      seizures were classified as cryptogenic in 62% (58-66%), remote symptomatic in
      21% (18-25%), and acute symptomatic in 15% (12-18%). The aetiology of epilepsy
      was vascular disease in 15% (12-18%) and tumour in 6% (4-8%). Among older
      subjects the proportion with an identifiable cause was much higher: 49% (41-58%)
      were due to vascular disease and 11% (6-16%) to tumour. Only 252 (45% [41-49%])
      of the 564 patients with definite epileptic seizures were registered at the time
      of their first seizure. 52% (48-56%) of the patients had partial or secondarily
      generalised seizures, and only 39% (35-43%) seizures generalised from the outset.

PMID- 1978114
TI  - National General Practice Study of Epilepsy: recurrence after a first seizure.
AB  - In the National General Practice Study of Epilepsy 564 patients classified as
      having definite seizures have been followed up for 2-4 years. 67% (95% confidence
      interval 63-71%) had a recurrence within 12 months of the first seizure, and 78%
      (74-81%) had a recurrence within 36 months. Seizures associated with a
      neurological deficit presumed present at birth had a high rate of recurrence
      (100% by 12 months), whereas seizures that occurred within 3 months of an acute
      insult to the brain, such as head injury or stroke, or in the context of an acute
      precipitant such as alcohol, carried a much lower risk of recurrence (40% [29
      51%] by 12 months). Other factors affecting the risk of recurrence were age-the
      highest risk being for patients under the age of 16 (83% [77-89%] by 36 months)
      or over the age of 59 (83% [76-90%] by 36 months-and type of first seizure-the
      risk of recurrence being much higher for patients with simple partial or complex
      partial seizures (94% [90-99%] by 36 months) than for those with generalised
      tonic clonic seizures (72% [67-77%] by 36 months).

PMID- 1978115
TI  - Comparison of oral iron chelator L1 and desferrioxamine in iron-loaded patients.
AB  - The efficacy of the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1) was
      compared with that of subcutaneous desferrioxamine in 26 patients with
      transfusional iron overload. Immediately after red-cell transfusion, 20 patients
      were randomised to receive either desferrioxamine (50 mg/kg daily as a 12 h
      subcutaneous infusion), or L1 (50 mg/kg daily by mouth). Patients were evaluated
      during treatment with the other drug after transfusion the next month. Mean (SD)
      daily urinary iron excretion was lower during L1 than during desferrioxamine
      (12.3 [6.7] vs 18.2 [15.3] mg/day). In 5 patients the dose of L1 was raised from
      50 to 75 mg/kg daily; mean urinary iron excretion rose from 13.8 (7.0) mg/day to
      26.7 (17.8) mg/day, comparable with that during desferrioxamine (24.9 [24.3]
      mg/day). Faecal iron excretion rose slightly over baseline in 6 patients studied
      during L1 administration (from 8.5 [0.9] mg/day to 12.2 [0.9] mg/day).
      Pharmacokinetic studies showed an elimination half-life for L1 of 117-237 min.
      Studies in dogs and in volunteers showed no absorption of the L1-iron complex,
      excluding a contribution of absorption of intraluminal complexes of L1 and food
      iron to urinary iron excretion. Further animal toxicity testing is needed before
      L1 can be studied in a broader group of patients.

PMID- 1978116
TI  - Cytomegalovirus and Rasmussen's encephalitis.
AB  - In-situ hybridisation with a biotinylated cytomegalovirus (CMV) DNA probe was
      done on brain biopsy specimens from 10 patients with Rasmussen's encephalitis
      (RE) and 46 age-matched control patients with other neurological diseases. All 10
      patients with RE had intractable epilepsy and focal neurological deficits, and
      there was perivascular cuffing, microglial nodules, astrogliosis, and neuronal
      loss. CMV genomic material was demonstrated in 7 of the 10 patients with RE (in
      neurons, astrocytes, oligodendrocytes, and endothelial cells) and in 2 of the 46
      control patients. Probes for herpes simplex virus and hepatitis B virus were
      negative in all patients and in fibroblast controls. The results suggest that CMV
      is a likely cause of Rasmussen's encephalitis.

PMID- 1978117
TI  - Traumatic injury of the heart.

PMID- 1978118
TI  - Protecting women out of their jobs.

PMID- 1978119
TI  - Fracture patterns revisited.

PMID- 1978120
TI  - Regulating ras.

PMID- 1978121
TI  - Physicianship.

PMID- 1978123
TI  - Acute hypervolaemic haemodilution to avoid blood transfusion during major
      surgery.
AB  - 16 patients underwent acute hypervolaemic haemodilution with dextran 40 and
      Ringers lactate, to see whether this procedure could avoid preoperative blood
      transfusion. Packed cell volume (PCV) and oxygen extraction decreased, and
      cardiac index and pulmonary wedge pressure increased, although end-systolic area
      was unchanged. PCV was not significantly different between patients who lost less
      than or greater than 20% of their initial blood volume. This preoperative
      manoeuvre, which reduces loss of red blood cells, allowed major surgery to be
      completed safely without blood transfusion.

PMID- 1978122
TI  - The fifth freedom revisited: II, The way forward.

PMID- 1978124
TI  - Child abuse of one of a pair of twins in Japan.
AB  - A nationwide survey in Japan on child abuse and neglect revealed that 10% of the
      victims were products of multiple births. None of the victims who were singletons
      had multiple-birth siblings, and only in a few cases were both twins abused. The
      findings indicated that one rather than both of a pair of twins was likely to be
      abused in Japan. Abuse of both twins was likely when there were serious parental
      or family problems, whereas abuse of one twin was associated with the child's
      medical problems or non-home care. There was no instance of abuse of a pair of
      twins when both were handicapped. Comparisons of the abused twin with the non
      abused co-twin and examination of the abuser's attitude to the victim suggested
      that the difference between twins in their development or in their response to
      parents increased the stress of child-rearing and encouraged favouritism, which
      resulted in abuse of only one twin. Comparison by parents of children with their
      siblings may be a common factor in general child abuse because it is a natural
      thing for parents to do.

PMID- 1978125
TI  - Bovine spongiform encephalopathy.

PMID- 1978126
TI  - Trade-off between gestational age and miscarriage risk of prenatal testing: does
      it vary according to genetic risk?
AB  - It has been generally assumed that as genetic risk rises, so the higher procedure
      related miscarriage rates of diagnostic tests done earlier in gestation become
      more acceptable. To test the hypothesis a decision tree was used, in which the
      only differences between two tests A and B were that A was carried out earlier in
      pregnancy and was more likely to cause miscarriage. Over a wide range of rankings
      for the three outcomes (procedure-related miscarriage of a normal baby, early
      termination of pregnancy after test A, late termination of pregnancy after test
      B), the expected utility (relative desirability) of an earlier, but more risky,
      test was greater at a high (1 in 4) than at a low (1 in 100) genetic risk.

PMID- 1978127
TI  - UK: HIV--future of social care.

PMID- 1978128
TI  - Food poisoning related to consumption of illicit beta-agonist in liver.

PMID- 1978129
TI  - Tragedy in an Australian desert.

PMID- 1978130
TI  - Overpopulation and death in childhood.

PMID- 1978131
TI  - Fish oil versus olive oil.

PMID- 1978132
TI  - Subacute sclerosing panencephalitis in the developing world.

PMID- 1978134
TI  - Airborne transmission of varicella-zoster virus in hospitals.

PMID- 1978133
TI  - Rotavirus infection and persistent diarrhoea in young children.

PMID- 1978135
TI  - Needlestick hepatitis C virus seroconversion in a surgeon.

PMID- 1978136
TI  - Severe malaria in a provincial hospital in Vietnam.

PMID- 1978137
TI  - Role of fetal blood gas analysis in intrauterine growth retardation.

PMID- 1978138
TI  - Registration of births of very low birthweight infants.

PMID- 1978139
TI  - Disc injuries in cervical trauma.

PMID- 1978140
TI  - Benzene in petrol.

PMID- 1978142
TI  - Genetics of pre-eclampsia.

PMID- 1978141
TI  - Typing of fetal platelet alloantigens when platelets are not available.

PMID- 1978143
TI  - DNA marker applicable to presymptomatic and prenatal diagnosis of
      facioscapulohumeral disease.

PMID- 1978144
TI  - Transient cardiac arrest during continuous intravenous infusion of apomorphine.

PMID- 1978145
TI  - Maharishi Ayur-Veda.

PMID- 1978146
TI  - Bristol Cancer Help Centre.

PMID- 1978147
TI  - Pancreatic islet transplantation.

PMID- 1978148
TI  - Medical care for Palestinians.

PMID- 1978149
TI  - PCR to detect toxoplasma.

PMID- 1978150
TI  - Selective reduction of quadruplet pregnancy at risk of beta-thalassaemia.

PMID- 1978151
TI  - Furunculosis and hypoferraemia.

PMID- 1978152
TI  - Osteoporosis reversal with transdermal progesterone.

PMID- 1978153
TI  - Ovulation induction and neural tube defects.

PMID- 1978154
TI  - Bone density screening for osteoporosis.

PMID- 1978155
TI  - Health risks of salmon sushi.

PMID- 1978156
TI  - HIV seroprevalence in a defined London population.

PMID- 1978157
TI  - Aetiology of Kaposi's sarcoma.

PMID- 1978158
TI  - Detection of Pneumocystis carinii.

PMID- 1978159
TI  - The laryngeal mask airway.

PMID- 1978160
TI  - Hepatitis A virus antibody in East Anglian blood donors.

PMID- 1978161
TI  - Treatment of short normal children with growth hormone--a cautionary tale?
AB  - 41 short normal children were randomly allocated either to daily injections of
      growth hormone (rhGH) at 30 IU/m2 per week or to no treatment. 6 months of rhGH
      therapy produced up to 76% loss of fat mass and up to 25% increase in lean body
      mass (LBM). These changes were significantly different from those in the
      untreated group. LBM was the main determinant of resting energy expenditure (REE)
      expressed as kJ/24 h. REE expressed as kJ/kg LBM per 24 h correlated negatively
      with height, which was responsible for 66% of the variance in REE kJ/kg LBM per
      24 h. Short children therefore expend more energy than tall children in
      fulfilling basic metabolic needs. After 6 months REE kJ/24 h increased
      significantly in treated children. However, treated children did not differ
      significantly from untreated children in REE kJ/kg LBM per 24 h. rhGH does not
      therefore seem to have a specific effect upon REE. The possibility that rhGH
      produces profound metabolic effects should limit its use in otherwise healthy
      children until the mechanism of action is more clearly elucidated.

PMID- 1978162
TI  - Binding to human jejunum of serum IgA antibody from children with coeliac
      disease.
AB  - Jejunal histology and the presence of serum IgA antibodies (JAB) binding to human
      jejunum in vitro were studied in 139 children with severe malabsorptive symptoms.
      Among 33 children with confirmed coeliac disease (ESPGAN criteria), 13 (93%) of
      14 sampled before starting on a gluten-free diet had JAB, none of 21 sampled had
      JAB while on a gluten-free diet of long duration, and 90% of 30 sampled during
      gluten challenge had JAB. 53 children had severe jejunal villous atrophy
      (probable coeliac disease): 71% of those younger than 2 years and 94% of those
      aged 2-18 years had JAB during gluten intake. JAB could not be detected in 53
      disease control patients (normal jejunal histology) and in 3 coeliac disease
      patients with selective IgA deficiency. Simultaneous determination of antigliadin
      (AGA) and antiendomysium (EMA) levels, and gliadin and tissue absorption studies,
      showed that JAB and AGA are different, whereas JAB and EMA are probably
      identical. IgA JAB could be the target-organ-related autoantibodies in coeliac
      disease.

PMID- 1978163
TI  - Protection against allergen-induced asthma by salmeterol.
AB  - The effects of the long-acting beta 2-agonist salmeterol on early and late phase
      airways events provoked by inhaled allergen were assessed in a group of atopic
      asthmatic patients. In a placebo-controlled study, salmeterol 50 micrograms
      inhaled before allergen challenge ablated both the early and late phase of
      allergen-induced bronchoconstriction over a 34 h time period. Salmeterol also
      completely inhibited the allergen-induced rise in non-specific bronchial
      responsiveness over the same time period. These effects were shown to be
      unrelated to prolonged bronchodilatation or functional antagonism. These data
      suggest novel actions for topically active long-acting beta 2-agonists in asthma
      that extend beyond their protective action on airways smooth muscle.

PMID- 1978165
TI  - Infective dermatitis of Jamaican children: a marker for HTLV-I infection.
AB  - In Jamaican children infective dermatitis is a chronic eczema associated with
      refractory nonvirulent Staphylococcus aureus or beta-haemolytic streptococcus
      infection of the skin and nasal vestibule. 14 children between the ages of 2 and
      17 years with typical infective dermatitis, attending the dermatology clinic at
      the University Hospital of the West Indies in Jamaica, were tested for antibody
      to human T-lymphotropic virus type 1 (HTLV-1). All were seropositive, whereas 11
      children of similar age with atopic eczema were all negative. In 2 of 2 cases of
      infective dermatitis, the biological mother was HTLV-1 seropositive. None of the
      14 patients showed signs of adult T-cell leukaemia/lymphoma, though experience
      with previous cases of infective dermatitis indicates the possibility of such
      progression.

PMID- 1978164
TI  - Effect of massive dose vitamin A on morbidity and mortality in Indian children.
AB  - The effect of vitamin A supplementation on preschool child morbidity and
      mortality was assessed in a prospective double-blind placebo-controlled study
      around Hyderabad, India. Every six months 200,000 IU vitamin A was given to 7691
      children (treatment group) whereas 8084 children received a placebo (control
      group). Morbidity and mortality data were collected every three months. Risk of
      respiratory infection was higher in children with mild xerophthalmia than in
      children with normal eyes. Vitamin A supplementation had no effect on morbidity
      status. Mortality rates were similar in the two groups; it was highest in
      children who did not receive either vitamin A or placebo. The findings suggest
      that vitamin A supplementation alone may not reduce child mortality.

PMID- 1978166
TI  - Vitamin A and malnutrition/infection complex in developing countries.

PMID- 1978167
TI  - Adhesion molecules in diagnosis and treatment of inflammatory diseases.

PMID- 1978168
TI  - Thyroxine replacement therapy--too much of a good thing?

PMID- 1978169
TI  - Any need for a chair of tropical surgery?

PMID- 1978170
TI  - Houses of recovery.

PMID- 1978172
TI  - Angiotensin-converting-enzyme inhibitors and anaphylactoid reactions to high-flux
      membrane dialysis.
AB  - In a retrospective study, 9 of 236 haemodialysis patients treated with high-flux
      polyacrylonitrile 'AN 69' membranes were found to have had anaphylactoid
      reactions. Treatment with angiotensin-converting-enzyme (ACE) inhibitors had been
      recently started in all 9 affected patients; only 5 of 227 unaffected patients
      had been treated with ACE inhibitors, and anaphylactoid reactions disappeared
      after discontinuation of ACE inhibitors.

PMID- 1978173
TI  - Foodborne viruses.

PMID- 1978171
TI  - Cerebral malaria in children.
AB  - Cerebral malaria is a rapidly progressive encephalopathy with up to 50%
      mortality. A cardinal feature is the massing of red cells containing mature
      Plasmodium falciparum within the cerebral capillaries. Adhesion of these
      parasitised red cells to endothelium, an event which may initiate cerebral
      malaria, is being studied at the molecular level. However, the relevance of these
      studies to the pathophysiology and treatment of human cerebral malaria is
      uncertain. Although chloroquine is still widely used to treat falciparum malaria,
      resistance has spread to most of the endemic zone. Quinine is emerging as the
      only effective treatment for cerebral malaria, though resistance to this drug
      threatens to become a problem. Alternative drugs are urgently needed.

PMID- 1978175
TI  - Benzodiazepine overprescribing: successful initiative in New York State.

PMID- 1978174
TI  - How AIDS forces reappraisal of hepatitis B virus control in sub-Saharan Africa.
AB  - For developing countries the cost-benefit of vaccination in the control of
      hepatitis B virus (HBV) infection is great since the acute infection is generally
      subclinical and the benefit is the prevention of small numbers of cases of
      cirrhosis and hepatocellular carcinoma. Since the pattern of HBV infection in
      Africa is such that, compared with south-east Asia, infection occurs later in
      childhood and spread is horizontal rather than vertical, investigation of the
      method of spread of HBV may result in a means of control other than by
      vaccination. In the meantime, because of the overlap in the means by which HBV
      and human immunodeficiency virus (HIV) are spread, it could be worthwhile taking
      advantage of existing AIDS prevention programmes to educate people about how to
      avoid both HBV and HIV infections.

PMID- 1978176
TI  - Women and HIV disease.

PMID- 1978177
TI  - Vitamin A and pregnancy.

PMID- 1978178
TI  - Fetal platelet counts in thrombocytopenic pregnancy.

PMID- 1978179
TI  - Inconsistencies in clinical decisions in obstetrics.

PMID- 1978180
TI  - Erythema nodosum and hepatitis C.

PMID- 1978181
TI  - Brachioradial delay.

PMID- 1978182
TI  - Heart attacks and sleep apnoea.

PMID- 1978183
TI  - Benzodiazepine-like molecules in human milk.

PMID- 1978184
TI  - Intestinal secretion in short bowel syndrome.

PMID- 1978185
TI  - What causes motoneuron disease?

PMID- 1978186
TI  - "Hanging spectacles" sign in stroke.

PMID- 1978187
TI  - Therapy in Helicobacter pylori infection.

PMID- 1978188
TI  - Is absence of sinus arrhythmia a useful marker of atrial fibrillation?

PMID- 1978189
TI  - Posture and blood tests.

PMID- 1978190
TI  - Toothpaste and Crohn's disease.

PMID- 1978191
TI  - Targeted therapy for recurrent breast carcinoma with regional
      'Lipiodol'/epirubicin infusion.

PMID- 1978192
TI  - Treatment of multiresistant typhoid fever.

PMID- 1978193
TI  - Kidneys for sale.

PMID- 1978194
TI  - Managing alcoholism in general practice.

PMID- 1978195
TI  - Quality of life after discharge from long-stay wards.

PMID- 1978196
TI  - Drug addiction: stars fall.

PMID- 1978197
TI  - One man's meat.

PMID- 1978198
TI  - Timing of transabdominal chorionic villus sampling.

PMID- 1978199
TI  - Effect of electrical nerve stimulation on dystonic tremor.

PMID- 1978200
TI  - PCR testing in HIV-1 seronegative haemophilia.

PMID- 1978201
TI  - Sensitivity for anti-HIV-2 of combined HIV antibody kits.

PMID- 1978202
TI  - Occupational infection among anaesthetists.

PMID- 1978203
TI  - Reactive arthritis after unusual Salmonella infections.

PMID- 1978204
TI  - When should hairy cell leukaemia be treated?

PMID- 1978205
TI  - Neuron-specific enolase as a marker for medulloblastoma.

PMID- 1978206
TI  - Predicting responses to interferon.

PMID- 1978207
TI  - Gemfibrozil-induced impotence.

PMID- 1978209
TI  - Clodronate as outpatient treatment for hypercalcaemia.

PMID- 1978208
TI  - Safety of contrast echocardiography in screening divers.

PMID- 1978210
TI  - Pneumomediastinum after belching.

PMID- 1978211
TI  - [Inhibition of plasma cholinesterase by pancuronium and vecuronium].
AB  - Plasma cholinesterase activity was measured in patients following administration
      of pancuronium and vecuronium at dosages of 0.1 mg/kg. Both agents produced
      significant reduction in the plasma cholinesterase activity (P less than 0.01).
      No statistically significant difference between the inhibitory effects of these
      drugs was observed.

PMID- 1978212
TI  - [Sulfasalazine in the treatment of ankylosing spondylitis].
AB  - Ninety-five patients with ankylosing spondylitis received either sulphasalazine
      (less than or equal to 3 g/day) or placebo for 24 weeks. The patients who
      received sulphasalazine showed significantly improved clinical parameters
      [duration of morning stiffness (p less than 0.05), the number of painful and
      swollen joints (less than 0.05)] and laboratory parameters [erythrocyte
      sedimentation rate (p less than 0.001), haptoglobin (p less than 0.05), IgG (p
      less than 0.05), IgA (p less than 0.001), IgM (p less than 0.05)]. No
      statistically significant differences were seen in the patients receiving
      placebo. The results suggest that sulphasalazine is effective for the treatment
      of patients with ankylosing spondylitis. In these patients, there was also a
      diminution of the daily dosage of nonsteroidal antiinflammatory drugs. In the
      majority of patients, clinical and laboratory improvements were expressed more
      pronouncedly in the peripheral form of ankylosing spondylitis than in the axial
      form, but statistically no significant differences were found between the two
      groups.

PMID- 1978213
TI  - Evidence of a new serine protease in the rat pure pancreatic juice that degrades
      somatostatin.
AB  - Somatostatin (SS) is found in the endocrine pancreas and has been reported in the
      pure pancreatic juice (PPJ) of different species. Characterization by gel
      filtration of immunoreactive SS (irSS) in the rat PPJ (rPPJ) results in a single
      peak corresponding to 23kDa molecular weight. Incubation of the 23kDa fraction
      with labeled or synthetic SS results in time dependent degradation of both
      peptides. This degradation is inhibitable by PMSF, calcium and by heat, whereas
      specific inhibitors of trypsin and chymotrypsin are without effect. These data
      suggest that irSS previously measured in rPPJ samples by RIA without confirmation
      of radioactive tracer stability may lead to false positive results. Indeed, our
      study indicates the presence of a 23kDa enzyme in the rPPJ degrading radiolabeled
      somatostatin during the RIA procedure. This putative new enzyme found into the
      rPPJ may thus be partially responsible for the apparent irSS presence.

PMID- 1978214
TI  - Effect of direct and indirect dopamine agonists on brain extracellular ascorbate
      levels in the striatum and nucleus accumbens of awake rats.
AB  - Systemic administration of direct and indirect dopamine agonists resulted in
      increased extracellular ascorbic acid levels in the striatum and, to a lesser
      degree, in the nucleus accumbens as measured by in vivo voltammetry.
      Intraperitoneal d-amphetamine sulfate (5mg/kg) increased ascorbate concentrations
      in striatal extracellular fluid. Amphetamine also increased extracellular
      ascorbate levels in the nucleus accumbens although more gradually and to a lesser
      extent. Intraperitoneal phenethylamine hydrochloride (20 mg/kg) following
      pargyline hydrochloride pretreatment (20 mg/kg) increased extracellular ascorbate
      levels in the striatum significantly above the small increase seen in the nucleus
      accumbens. The direct acting dopamine agonists Ly-141865 and Ly-163502 when given
      i.p. at 1 mg/kg, resulted in increased extracellular ascorbate concentrations in
      both brain areas, again with a significantly greater effect in the striatum.
      These results indicate that brain extracellular ascorbate levels can be modulated
      by dopaminergic neuro-transmission and that this modulation is quantitatively
      different in different dopamine-containing brain structures.

PMID- 1978215
TI  - Intrathecal somatostatin produces effects dependent on the interval between
      catheter implantation and drug injection.
AB  - Intrathecal (i.t.) injection of somatostatin has been reported to depress
      nociceptive reflexes as well as to cause severe disturbance of somatomotor
      performance. The present study was designed to assess the dependence of these
      effects on the dose and the interval between implantation of the catheter and
      i.t. injection of somatostatin in rats. The effects produced by i.t. injection of
      somatostatin consisted of an increase in the response latencies of nociceptive
      responses to noxious heat, impairment of motor performance and grooming behavior,
      convulsions, and death. Except for grooming behavior, these were related in
      incidence and degree to the dose and the interval, the potency of somatostatin
      being highest at short intervals. Sham operations also affected the effectiveness
      of somatostatin.

PMID- 1978216
TI  - Inhibition by enkephalin of medial vestibular nucleus neurons responding to
      horizontal pendular rotation.
AB  - Electrophysiological studies were performed to determine whether or not
      enkephalin modulates the activities of medial vestibular nucleus (MVN) neurons
      responding to horizontal pendular rotation using alpha-chloralose anesthetized
      cats. The effects of microiontophoretically applied drugs were examined in type I
      and type II neurons identified according to responses to horizontal, sinusoidal
      rotation; type I and type II neurons showed an increase and decrease in firing
      with rotation ipsilateral to the recording site and vice versa with contralateral
      rotation, respectively. Iontophoretic application of enkephalin suppressed spike
      firing induced by rotation of the animals in type I neuron, but not in type II
      neuron. The spike firing induced by iontophoretically applied glutamate was also
      inhibited during the application of enkephalin. The inhibition by enkephalin of
      both rotation- and glutamate-induced firing was antagonized by naloxone which was
      given simultaneously. These results suggest that enkephalin acts on MVN type I
      neuron to inhibit transmission from the vestibule, thereby controlling vestibulo
      ocular reflex.

PMID- 1978218
TI  - [XII All-Union Congress of Rentgenologist and Radiologist].

PMID- 1978217
TI  - Selective effect on punished versus unpunished responding in a conflict test as
      the criterion for anxiogenic activity.
AB  - The punished drinking test has been used successfully for identifying and
      studying anxiolytic agents. By reducing the level of punishment (i.e., decreasing
      the intensity of shock), it has also been used as a method for measuring
      anxiogenic activity. Because anxiogenic behavior is a novel and important concept
      that is not yet fully established, we have reinvestigated the effects of two
      putative inverse benzodiazepine agonists and pentylenetetrazol in this conflict
      test. In a series of experiments, using both our version of the procedure and a
      replication of a previously published method, we were unable to demonstrate a
      selective reduction in punished responding over unpunished responding caused by
      CGS 8216 (3 to 40 mg/kg), FG 7142 (2 to 6 mg/kg), and pentylenetetrazol (10 to 20
      mg/kg) as reported previously. A careful comparison of the details of our method
      and the published procedure failed to reveal the source of this discrepancy. If
      anxiogenic behavior is to be defined as a selective effect of a drug on punished
      response, the value of this test will depend on identification of its critical
      variables.

PMID- 1978219
TI  - Using discrete plantar skin mounted sensors on a single foot.

PMID- 1978221
TI  - Direct gene diagnosis of cystic fibrosis by allele-specific polymerase chain
      reactions.
AB  - Cloning of the cystic fibrosis gene and the identification of the predominant
      disease-causing mutation did not only help in the understanding of this frequent
      disease, but was immediately followed by applications in direct gene diagnosis.
      We describe a method for the detection of the so-called delta F508 deletion,
      which accounts for 70% of the mutations: a polymerase chain reaction with two
      different combinations of oligonucleotide primers, which discriminate between
      mutant and wild-type alleles. This allele-specific amplification provides a
      rapid, non-radioactive and very reliable method for direct genotyping.
      Establishment of the procedure and its application in diagnosis are described. We
      further report preliminary data on the frequency of this mutation in German
      patients and its association with restriction fragment length polymorphism
      haplotypes.

PMID- 1978220
TI  - T cell recognition of stress proteins. A link between infectious and autoimmune
      disease.
AB  - Exposure of any living cell to a change in environmental conditions such as
      increased growth temperature results in the induction of stress, or "heat shock",
      proteins. Proteins identified in such experiments have subsequently been shown to
      be ubiquitous components of all cells and to perform essential functions during
      normal cell growth in addition to their role during stress. It has recently been
      recognized that members of stress protein families play an important role in the
      immune response to a wide variety of infections, and the highly conserved nature
      of such proteins has led to the suggestion that they may also be immune targets
      in autoreactive responses. In this article we review the role of stress proteins
      in the immune response to infection and discuss the evidence which suggests that
      lymphocytes recognizing conserved determinants on such antigens may be associated
      with autoimmune diseases.

PMID- 1978222
TI  - Genetic variation at the omp2 porin locus of the brucellae: species-specific
      markers.
AB  - The omp2 locus of Brucella abortus is composed of two closely related genes
      (omp2a and omp2b) that encode, and potentially both express, homologous porin
      proteins. Genetic variation at this locus is revealed in the form of restriction
      fragment-length polymorphisms which can be used to distinguish the type strains
      of all six Brucella species. Five of the six species contain single copies of
      omp2a and omp2b, whereas Brucella ovis appears to have two copies of the omp2a
      gene. The implications of these results with regard to the physiological
      functions of the omp2a and the omp2b gene products, phylogeny of the genus, and
      species-specific adaptation are discussed.

PMID- 1978223
TI  - Immunocytochemical analysis of P-fimbrial structure: localization of minor
      subunits and the influence of the minor subunit FsoE on the biogenesis of the
      adhesin.
AB  - Antibodies recognizing the non-adhesive minor P-fimbral subunit protein E and the
      P-fimbrial adhesin were used in an immunocytochemical analysis of P-fimbrial
      structure. It was demonstrated that P-fimbriae of the serotypes F71, F72 and F11
      carry their adhesin in a complex with protein E. These complexes are commonly
      found at the tip of the fimbrial structure. In P-fimbriae of serotype F9,
      expressed by the uropathogenic Escherichia coli strain 21086, adhesin-protein E
      complexes are localized at the tips as well as along the shafts of the fimbriae.
      Protein E of F71 fimbriae (FsoE) plays a catalysing role in the biogenesis of the
      adhesin, but has no effect on the eventual localization of the adhesin.

PMID- 1978224
TI  - Role of insulin in the blunted glucose metabolic response of septic rats to
      epinephrine.
AB  - Epinephrine produces smaller incremental increases in plasma glucose
      concentration and rate of glucose appearance (Ra) in septic rats compared with
      nonseptic animals. In the present study, we investigated the role of insulin in
      the diminished response of septic rats to epinephrine-induced increases in
      glucose turnover. Glucose kinetics were assessed by the infusion of [6-3H]
      glucose in conscious catheterized rats made septic by subcutaneous injections of
      live Escherichia coli. Epinephrine was infused at 1 micrograms/min/kg for 2 hours
      in the presence and absence of somatostatin and mannoheptulose (SRIF + MH). In
      comparison to nonseptic control animals, epinephrine-induced increases in plasma
      glucose concentration and glucose Ra were blunted by more than 50% in the septic
      rats. Infusion of SRIF + MH with epinephrine restored the blunted response to
      normal. During the infusion of epinephrine alone, the plasma insulin
      concentration in the septic rats was 2.8-fold higher than the nonseptic controls.
      SRIF + MH lowered the plasma insulin concentrations in both the nonseptic and
      septic rats to less than 10 microU/mL. SRIF + MH reversed the sepsis-induced
      hyperglucagonemia, but did not prevent a slight increase in glucagon levels
      during the epinephrine infusion in the nonseptic rats. In a second study, septic
      rats infused with SRIF + MH and replacement insulin showed a smaller increase in
      glucose concentration and glucose production in response to epinephrine than did
      septic animals administered SRIF + MH and no insulin. These results indicate that
      insulin plays an important role in the diminished response of septic rats to
      epinephrine.

PMID- 1978225
TI  - Determination of carbonyl content in oxidatively modified proteins.

PMID- 1978226
TI  - Asthma therapy and mortality.

PMID- 1978227
TI  - Use of antiasthmatic drugs in Australia.
AB  - Bronchodilator prescription and sales data for Australia from 1975 to 1986 were
      analysed. Inhaled beta-agonists were the most commonly prescribed antiasthmatic
      agents in 1986, followed by sustained-release theophylline and inhaled
      corticosteroids. Marked increases in prescription sales of these three drug
      groups over the period were noted. We estimate that non-prescription sales of
      salbutamol inhalers increased by 410% between 1980 and 1986 (P less than 0.01).
      Prescribing rates by general practitioners for beta-agonists, sustained-release
      theophylline and inhaled corticosteroids increased from 1979 to 1986. Prescribing
      rates of beta-agonists were highest for persons aged 1-11 years and 55 years and
      over, and increased markedly for children aged 1-11 years over the period. For
      sustained-release theophylline, prescribing rates were highest for persons 55
      years and over. The difficulties in postulating possible relationships between
      prescribing trends and asthma mortality are discussed.

PMID- 1978228
TI  - The use of verapamil to treat box-jellyfish stings.

PMID- 1978229
TI  - [Crohn disease and ulcerative colitis].

PMID- 1978230
TI  - Dezocine.

PMID- 1978231
TI  - Medical, psychological and social aspects of torture: prevention and treatment.

PMID- 1978233
TI  - [Comparison of the antihypertensive effects of bopindolol and metoprolol in the
      treatment of arterial hypertension].
AB  - A randomized, double blind clinical trial included 40 hypertension patients of
      both sexes, aged 18-70 years, with diastolic blood pressure persistently above
      100 (13.33 kPa) and below 120 mm Hg (15.99 kPa). After a run-in period on
      placebo, one half of them was treated with bopindolol (single daily dose 1-3 mg),
      and the other half with metoprolol (100-300 mg daily in two divided doses). After
      4 weeks of formal trial both beta blockaders had significantly decreased the
      elevated arterial pressure, e.g. the mean arterial pressure in the bopindolol
      group dropped from an average of 129.1 +/- 6.9 (17.20 +/- 0.92) to 111.6 +/- 6.1
      mm Hg (14.87 +/- 0.81 kPa) or by 13.6% and in the metoprolol group from 129.8 +/-
      7.1 (17.30 +/- 0.94 kPa) to 114.5 +/- 6.4 mm Hg (15.26 +/- 0.85 kPa) or by 11.8%
      (p less than 0.02). After 12 weeks the mean pressure was ulteriorly lowered to
      some 104.3 mm Hg (13.90 kPa) on bopindolol and to some 106.0 mm Hg (14.12 kPa) on
      metoprolol. The heart rate was expectedly slowed down, from an average of 95 to
      69 b.p.m. with bopindolol (27.4% decrease, p less than 0.001) and from 99 to 67
      b.p.m. with metoprolol (32.3% decrease, p less than 0.001). The other parameters,
      including the laboratory results did not change appreciably during this study.
      Clinically relevant side-effects were not registered, and the observed between
      group differences did not reach the level of statistical significance. It is
      concluded that bopindolol and metoprolol are beta-adrenergic blockaders of
      comparable antihypertensive efficacy.

PMID- 1978232
TI  - Treatment of refractory and relapsed Hodgkin's disease: intensive chemotherapy
      and autologous bone marrow or peripheral blood stem cell support.
AB  - Thirty-three patients with recurrent or refractory Hodgkin's disease were treated
      with high-dose cyclophosphamide, BCNU, and etoposide and supported with either
      autologous bone marrow or peripheral blood stem cells or both. Peripheral blood
      stem cells were comparable to bone marrow in supporting the recovery of
      hematopoiesis. Twenty-five patients (76%) were in complete remission following
      this therapy of whom 13 have subsequently relapsed. Twelve remain alive and
      disease free from 10 to 47 months. The Kaplan-Meier estimate of disease-free
      survival at 28 months for the entire 33 patients is 32% (95% confidence interval,
      13-50%). Poor outcome in six patients was associated with bone marrow involvement
      by Hodgkin's disease at the time of peripheral blood stem cell collection. These
      six patients' survival, disease-free survival, the duration of complete remission
      were all significantly worse than for the 27 patients who were supported with
      bone marrow (n = 23), peripheral blood stem cells (n = 2), or both (n = 2), and
      whose marrows were free of disease at the time of stem cell collection. These
      data demonstrate that intensive therapy with autologous transplantation can
      produce extended disease-free survival for some patients with advanced Hodgkin's
      disease and that peripheral blood stem cell support can effectively be used for
      hematopoietic reconstitution. However, our observations also suggest that with
      this preparative regimen, bone marrow involvement at the time of peripheral blood
      stem cell collection is predictive for a poor outcome and alternate approaches to
      treatment should be considered for this subset of patients.

PMID- 1978235
TI  - Physician assistants. Don't call me doctor.

PMID- 1978234
TI  - Keeping tabs on prescription writers.

PMID- 1978236
TI  - [90th Congress of the Japan Surgical Society. Sapporo, 16-18 May 1990.
      Abstracts].

PMID- 1978237
TI  - Molecular cloning and characterization of alc the gene encoding allantoicase of
      Neurospora crassa.
AB  - Purines can be utilized as a secondary nitrogen source by Neurospora crassa
      during conditions of nitrogen limitation. The expression of purine catabolic
      enzymes is governed by the nitrogen regulatory circuit and requires induction by
      uric acid. The major positive-acting nitrogen regulatory gene, nit-2, turns on
      the expression of the purine catabolic enzymes, which may also be subject to
      negative regulation by a second control gene, nmr. We have cloned alc, the
      structural gene which encodes allantoicase, an inducible enzyme of the purine
      degradative pathway. The identity of the alc clone was confirmed by restriction
      fragment length polymorphism analysis and by repeat-induced mutation. The alc
      gene is transcribed to give a single messenger RNA, approximately 1.2 kb in
      length. The negative-acting nmr gene affects the expression of alc in the
      expected manner. Both the nit-2 and the nmr control genes affect alc mRNA levels
      and allantoicase enzyme activity in both the induced and nitrogen-repressed
      conditions.

PMID- 1978238
TI  - Tc1 transposition and mutator activity in a Bristol strain of Caenorhabditis
      elegans.
AB  - In most strains of Caenorhabditis elegans with a low copy number of Tc1
      transposable elements, germline transposition is rare or undetectable. We have
      observed low-level Tc1 transposition in the genome of the C. elegans var. Bristol
      strain KR579 (unc-13[e51]) resulting in an increase in Tc1 copy number and
      subsequent mutator activity. Examination of genomic blots from KR579 and KR579
      derived strains revealed that more Tc1-hybridizing bands were present than in
      other Bristol strains. A novel Tc1-hybridizing fragment was cloned from a KR579
      derived strain. Unique sequence DNA flanking the Tc1 element identified a 1.6 kb
      restriction fragment length difference between the KR579 and N2 strains
      consistent with a Tc1 insertion at a new genomic site. The site of insertion of
      this Tc1 was sequenced and is similar to the published Tc1 insertion site
      consensus sequence. Several isolates of KR579 were established and maintained on
      plates for a period of 3 years in order to determine if Tc1 copy number would
      continue to increase. In one isolate, KR1787, a further increase in Tc1 copy
      number was observed. Examination of the KR1787 strain has shown that it also
      exhibits mutator activity as assayed by the spontaneous mutation frequency at the
      unc-22 (twitcher) locus. The KR579 strain differs from most low copy number
      strains in that it exhibits low-level transposition which has developed into
      mutator activity.

PMID- 1978239
TI  - Chromosomal analysis of Nicotiana asymmetric somatic hybrids by dot blotting and
      in situ hybridization.
AB  - A species-specific, dispersed repetitive DNA sequence was cloned from Nicotiana
      plumbaginifolia and used in dot blots and in situ hybridizations to analyze
      asymmetric somatic hybrids of N. tabacum(+)kanamycin-resistant N.
      plumbaginifolia. Dot blot hybridization data, using the cloned, species-specific
      repetitive DNA as a probe, showed that some of the hybrids contain only 1%-5% N.
      plumbaginifolia DNA, whereas others contain 15%-25%. In situ hybridization of the
      probe to chromosome spreads showed that the extremely asymmetric hybrids retain a
      single N. plumbaginifolia chromosome; the hybrids with higher dot blot values
      were found to have 8 to 12 N. plumbaginifolia chromosomes and chromosome
      fragments. In situ hybridization also revealed translocations between N.
      plumbaginifolia and N. tabacum chromosomes in 3 of 8 hybrids studied. RFLP
      analysis using a 5S gene probe showed the presence of N. plumbaginifolia-specific
      5S banding patterns in most hybrids examined, including those that retain only a
      single N. plumbaginifolia chromosome.

PMID- 1978240
TI  - Agonist-induced desensitization of D1-dopamine receptors linked to adenylyl
      cyclase activity in cultured NS20Y neuroblastoma cells.
AB  - NS20Y neuroblastoma cells expressing a homogeneous population of D1-dopamine
      receptors were used in the present study as a model system to investigate the
      mechanisms of agonist-induced stimulation and desensitization of D1 receptor
      coupled adenylyl cyclase activity. Membrane prepared from NS20Y cells showed a
      pharmacologically specific, dose-dependent increase in cAMP production in
      response to various dopaminergic agonists. Dopamine exhibited an EC50 of 5
      microM, and at 100 microM a maximal stimulation of 3-4-fold over basal enzyme
      activity was observed, which could be selectively antagonized by the active
      stereoisomers of SCH-23390 and butaclamol. Preincubation of NS20Y cells with
      dopamine induced homologous desensitization of D1 receptor-coupled adenylyl
      cyclase activity, decreasing dopamine- but not prostaglandin-, adenosine-, or
      forskolin-stimulated cAMP production. Desensitization did not affect the EC50 for
      dopamine but resulted in an 85-90% reduction in the maximal response. Dopamine
      induced desensitization of adenylyl cyclase activity was found to be both dose
      and time dependent. As early as 5 min after preincubation with dopamine, cAMP
      production was decreased by 45-50%, with maximal desensitization occurring by 90
      min. Preincubation of NS20Y cells with dopamine also induced a decrease in D1
      receptor ligand binding activity, as assessed with the radiolabeled antagonist
      [3H]SCH-23390. This decrease in binding activity occurred more slowly than the
      loss of enzyme activity, not achieving maximal levels until after 3 hr. [3H]SCH
      23390 saturation binding isotherms in control and maximally desensitized NS20Y
      cell membranes revealed no change in affinity (KD); however, a 65-70% decrease in
      receptor number (Bmax) was observed. Because the maximal and temporal decrease in
      D1 receptors does not correlated with the decrease in dopamine-stimulated enzyme
      activity, the desensitization may involve a functional uncoupling of the D1
      receptor in addition to receptor down-regulation. This is further suggested by a
      loss in high affinity agonist binding observed in agonist/[3H]SCH-23390
      competition experiments after desensitization. Removal of dopamine after maximal
      desensitization/down-regulation results in recovery to control values by 24 hr.
      This recovery is mostly, but not completely, blocked by protein synthesis
      inhibitors, suggesting an involvement of receptor degradation in the
      desensitization process.

PMID- 1978241
TI  - Inactivation of tyrosine hydroxylase by pterin substrates following
      phosphorylation by cyclic AMP-dependent protein kinase.
AB  - We reported previously that, following phosphorylation by cyclic AMP-dependent
      protein kinase, tyrosine hydroxylase in rat corpus striatal extracts is
      inactivated in a time-dependent and apparently irreversible fashion. Removal of
      low molecular weight substances from these extracts by gel filtration attenuates
      this inactivation. We tried to determine the identity of endogenous metabolites
      that promote inactivation of tyrosine hydroxylase under our experimental
      conditions. In the present study, we report that the reducing co-substrate
      tetrahydrobiopterin and its analogues promoted this irreversible inactivation.
      The concentration that produced a 50% loss of activity (at 20 min) of the
      phosphorylated enzyme was 0.7 microM and that for the unphosphorylated enzyme was
      420 microM. Using enzyme purified from a rat pheochromocytoma, we found that
      tyrosine, alpha-methyl-p-tyrosine, and a 3-iodotyrosine protected the
      phosphorylated enzyme against the inactivation produced by tetrahydrobiopterin.
      Catecholamines (dopamine, norepinephrine, epinephrine, and some of their
      analogues) also nullified inactivation. In contrast, the product of the reaction,
      dihydroxyphenylalanine, failed to attenuate the inactivation process. We
      performed several studies to ascertain the mechanism of inhibition by
      tetrahydrobiopterin. We considered the possibility that it formed reactive free
      radicals that produced inhibition. Free radical scavengers, however, failed to
      block the inhibition produced by tetrahydrobiopterin. Superoxide dismutase,
      catalase, and peroxidase also failed to protect tyrosine hydroxylase against
      inactivation. Moreover, when the experiments were performed under anaerobic
      conditions, the inactivation process was unaffected. These results suggest that
      reactive oxygenated species were not required for inactivation by
      tetrahydrobiopterin.

PMID- 1978242
TI  - Transcriptional program coordination by N-methyl-D-aspartate-sensitive glutamate
      receptor stimulation in primary cultures of cerebellar neurons.
AB  - In primary cultures of rat cerebellar neurons, a brief stimulation of glutamate
      receptors results in coordinated activation of a programmed early gene response
      involving increases in the amount of c-fos, c-jun, jun-B, and zif/268 mRNAs. Each
      of these genes was induced to a different extent and showed a temporal pattern
      characterized by either a monophasic "early" response, occurring within 30 min of
      glutamate addition, or a biphasic response (c-jun), lasting for up to 6 to 8 hr
      after the initial stimulus. The early phase of the glutamate-induced gene
      expression was prevented by 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid,
      a highly selective isosteric antagonist of the N-methyl-D-aspartate (NMDA)
      sensitive glutamate receptor (NMDA receptor). The second phase of the c-jun
      response was not blocked when the NMDA receptors were completely inhibited after
      the initial pulse of agonist or when the quisqualate-kainate receptor antagonist
      6-cyano-7-nitroquinoxaline-2,3-dione was added, suggesting that a brief NMDA
      receptor stimulation triggers a cascade of events critical for the manifestation
      of the delayed c-jun expression. Furthermore, gel retardation assays demonstrated
      that NMDA receptor activation results in a prolonged increase in nuclear DNA
      binding activity specific for the AP-1 transcriptional regulatory element.
      Protein immunoblot analysis showed that the composition of this nucleoprotein
      complex changes as a function of time, reflecting a cascade that involves an
      increased translation of Fos and several Fos-related proteins. The coordinated
      induction of several different transcription factors and the variations in
      transcriptional complex formation initiated by NMDA receptor stimulation may be a
      key mechanism in the orchestration of specific target gene expression that
      underlies various aspects of neuronal function, including plasticity responses.

PMID- 1978243
TI  - Competitive inhibition of magnesium-induced [3H]N-(1-[thienyl]
      cyclohexyl)piperidine binding by arcaine: evidence for a shared spermidine
      magnesium binding site.
AB  - The polyamine competitive antagonist arcaine (1,4-diguanidino-butane) produced
      complete inhibition of basal [3H]N-(1-[thienyl] cyclohexyl)piperidine ([3H]TCP)
      binding, with an IC50 value of 4.52 +/- 0.93 microM. Arcaine (5 and 10 microM)
      produced a decrease in the affinity without a significant change in the receptor
      density of [3H]TCP binding under equilibrium conditions. In addition, arcaine did
      not alter either N-methyl-D-aspartate-specific [3H] glutamate or strychnine
      insensitive [3H]glycine binding. Furthermore, increasing concentrations of
      arcaine produced parallel rightward shifts in the concentration-response curves
      for both spermidine- and magnesium-induced [3H]TCP binding, suggesting that
      arcaine is a competitive inhibitor of both agonists. Similar rightward shifts
      were observed for barium- and strontium-induced [3H]TCP binding. In contrast,
      arcaine decreased the efficacy of glutamate- and glycine-induced [3H]TCP binding
      without changing their EC50 values, indicating a noncompetitive type of
      inhibition. These results imply that spermidine and certain divalent cations
      including magnesium share the same mechanism for enhancing [3H]TCP binding,
      whereas glutamate and glycine have different sites of action. This is further
      supported by the additive effect of spermidine when tested in the presence of
      maximal concentrations of glutamate and glycine. On the other hand, spermidine
      and magnesium were not additive and, in fact, magnesium was able to block the
      effects of spermidine under certain conditions. The possibility that magnesium is
      a partial agonist at the polyamine site is discussed.

PMID- 1978244
TI  - Two pharmacologically distinct alpha 1-adrenoceptor subtypes in the contraction
      of rabbit aorta: each subtype couples with a different Ca2+ signalling mechanism
      and plays a different physiological role.
AB  - Using the alpha 1-adrenoceptor subtype-selective antagonists chlorethylclonidine
      (CEC), WB4101, and 5-methyl-urapidil, we have examined the possible heterogeneity
      in the alpha 1-adrenoceptor populations in rabbit aorta. The alpha 1-adrenoceptor
      alkylating agent CEC selectively inhibited the phasic component of the
      norepinephrine-induced contractile response, with little effect on the tonic
      component. The alpha 1-adrenoceptor occupancy-response relationship defined by
      the phenoxybenzamine inactivation method was rectangular hyperbolic for the tonic
      response, whereas that for the phasic response was linear, indicating the
      different degree of receptor reserve for the two responses. Radioligand binding
      studies with the nonselective alpha 1-adrenoceptor antagonist radioligand 125I
      BE2254 showed that 73-87% of the binding sites in rabbit aorta are CEC sensitive
      and they are predominantly low affinity sites both for WB4101 (pKd = 8.1) and for
      5-methylurapidil (pKd = 7.1). Moreover, alpha 1-adrenoceptor-mediated
      phosphatidylinositol (PI) hydrolysis was CEC sensitive, and fractional
      inactivation of alpha 1 receptors with CEC showed equivalent increments in the
      reduction of PI hydrolysis and phasic contractile response, suggesting that both
      responses are linearly related to the CEC-sensitive receptor sites. The Schild
      plots for the competitive antagonists WB4101 and 5-methyl-urapidil against alpha
      1a-adrenoceptor-selective agonist methoxamine-induced contraction were linear and
      had slopes not significantly different from unity, with a pA2 of 9.07 +/- 0.07 (n
      = 5) for WB4101 and 9.09 +/- 0.05 (n = 3) for 5-methyl-urapidil. However, the
      Schilod plots for these antagonists against norepinephrine were curvilinear.
      Computer-assisted analysis of these curvilinear Schild plots in a two-receptor
      system indicated that alpha 1-adrenoceptor populations responsible for the
      constrictive response are predominantly (approximately 80-90%) low affinity sites
      for the two antagonists (pKd approximately 8.1 for WB4101 and pKd approximately
      7.1 for 5-methyl-urapidil) and a small population (approximately 10-20%) are high
      affinity sites (pKd approximately 9.1 for both WB4101 and 5-methyl-urapidil),
      which was in good agreement with radioligand binding studies.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 1978245
TI  - Splicing precedes polyadenylation during Drosophila E74A transcription.
AB  - The E74 gene is one of a small set of early genes induced by the steroid hormone
      ecdysone at the onset of metamorphosis in the fruit fly, Drosophila melanogaster.
      This complex gene directs the synthesis of a 60-kilobase (kb) primary transcript
      that is spliced to form the 6-kb E74A mRNA. In a previous study, we found that
      ecdysone directly activates the E74A promoter and determined that RNA polymerase
      II transcribes this gene at a rate of approximately 1.1 kb/min. This elongation
      rate accounts for most of the 1-hour delay seen between the addition of ecdysone
      and the appearance of cytoplasmic E74A mRNA (C. S. Thummel, K. C. Burtis, and D.
      S. Hogness, Cell 61:101-111, 1990). We show here that nascent E74A transcripts
      are spliced, and we propose a model for the order of that splicing. This study
      provides, for the first time, direct biochemical evidence for splicing of a low
      abundance cellular RNA before transcription termination and polyadenylation.

PMID- 1978246
TI  - Linkage relationships of human arginine vasopressin-neurophysin-II and oxytocin
      neurophysin-I to prodynorphin and other loci on chromosome 20.
AB  - The structural genes for human prepro-arginine-vasopressin-neurophysin II (prepro
      AVP-NPII; ARVP) locus and prepro-oxytocin-neurophysin-I (prepro-OT-NPI; OT) locus
      are closely linked separated by only 12 kilobasepairs of DNA. These two loci have
      been assigned to chromosome 20 by previous studies of somatic cell hybrids. We
      used Southern blots to analyze a restriction fragment length polymorphism
      detected by a probe for prepro-OT-NPI to determine the linkage relationships for
      the ARVP/OT loci using samples from the Centre d'Etude du Polymorphisme Humain
      (Paris, France) collection of families. The ARVP/OT loci demonstrated extremely
      close linkage with the prodynorphin (PDYN) locus, with no recombinants (theta of
      0) and a log10 odds score of 5.2. Previous observations have shown the ARVP and
      PDYN peptides to be coexcreted in the same neurosecretory granules of some
      pituitary axons and that increased transcription of both genes occurs with
      osmotic stimulation. The combined ARVP/PT/PDYN group was also found to
      demonstrate linkage with other anonymous DNA segments on chromosome 20, including
      D20S4, D20S5, and D20S6. Using multilocus linkage analysis, the ARVP/OT loci map
      to the distal short arm of chromosome 20 about 15 centimorgans toward the
      telomere from the D20S5 locus, which is located near the middle of the short arm
      at 20p 12.21. These linkage relationships establish that the secretory and
      transcriptional associations of ARVP and PDYN extend to a close physical
      relationship in the human genome. Furthermore, the restriction fragment length
      polymorphism detected by these loci can serve as accurate markers in segregation
      studies of putative defects involving the OT, ARVP, or PDYN loci as well as
      provide a tool for studying the location of other genes, such as GH-releasing
      hormone.

PMID- 1978247
TI  - Exon 7 Ncol restriction site within CYP21B (steroid 21-hydroxylase) is a normal
      polymorphism.
AB  - A point mutation within exon 7 producing an amino acid coding change and a
      recognition site for the endonuclease Ncol has been reported in the HLA-Bw47
      linked CYP21A pseudogene and some mutant CYP21B (steroid 21-hydroxylase) genes of
      patients with congenital adrenal hyperplasia (CAH). Whether this mutation is
      deleterious was not demonstrated. We analyzed DNA from various subjects for the
      presence of the exon 7 Ncol site: group 1, 10 normal subjects; group 2, 11
      patients with salt-losing CAH; and group 3, 18 members of an Amish pedigree in
      which 10 expressed HLA-Bw47 not linked to CAH. Southern blots of Ncol-digested
      genomic DNA which were hybridized with CYP21 cDNA showed that four subjects of
      group 1 had a heterozygous Ncol pattern. In group 2, seven patients had the Ncol
      site; two of them were homozygous for the site and had deletions of both CYP21B
      genes. The other five were heterozygous for the Ncol site, which was linked to a
      CYP21B deletion and a HLA-Bw47 haplotype. In group 3, no one exhibited the exon 7
      Ncol site. To map the Ncol sites to CYP21A or CYP21B in the normal subjects, DNA
      from the four Ncol heterozygous subjects was double digested with Ncol and Mbol
      and hybridized with CYP21 cDNA. Ncol-Mbol fragments unique to CYP21A were
      identified in all four, but the smaller CYP21B-specific fragments were not
      detected. Their genomic DNA in the region of exon 7 (bases +1167 to +2058) was
      then amplified, cloned, and sequenced.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1978249
TI  - Restriction fragment length polymorphisms in the ribosomal gene spacers of
      Trypanosoma cruzi and Trypanosoma conorhini.
AB  - The ribosomal RNA genes of two species of Trypanosoma, Trypanosoma cruzi, the
      etiological agent of Chagas' disease, and Trypanosoma conorhini, a non-pathogenic
      rodent trypanosome, were cloned and partially characterized. The physical maps
      derived for their rRNA genes were similar throughout the region that encompasses
      the SSU-and LSU-rRNA coding sequences. However, the non-transcribed spacer DNA of
      both T. cruzi and T. conorhini was found to be polymorphic for several
      restriction enzyme sites. We show that strains of T. cruzi can be typed according
      to the characteristic restriction fragment length polymorphism of their NTS DNAs.

PMID- 1978248
TI  - Purification, cloning, and tissue distribution of a 23-kDa rat protein isolated
      by morphine affinity chromatography.
AB  - A 23-kDa (p23k) rat brain protein was stereospecifically eluted from a 14 beta
      bromoacetamidomorphine affinity column, purified to apparent homogeneity by
      reverse phase HPLC, and partially sequenced. Three degenerate
      oligodeoxynucleotide probes were synthesized based on this partial amino acid
      sequence. A rat brain cDNA library was screened using these probes, and a full
      length cDNA was isolated. The deduced protein, 187 amino acids long, is rich in
      glutamic and aspartic acid residues, endowing p23k with a net negative charge at
      neutral pH. The protein lacks a signal sequence as well as any transmembrane
      domains. Based on predictions of secondary structure, p23k is a globular protein
      composed of 30% alpha-helices and 18% beta-pleated sheets. Northern blot analysis
      revealed p23k transcripts in rat brain, liver, and the mouse x rat neuroblastoma
      glioma NG108-14 cell line. Although not an opioid receptor itself, this protein
      may be associated with such a receptor or be related to a protein that has been
      shown to be cross-linked to the opioid peptide beta-endorphin.

PMID- 1978250
TI  - Histamine2-receptor antagonists. Standard therapy for acid-peptic diseases. 1.

PMID- 1978251
TI  - Identification of the primary gene defect at the cytochrome P450 CYP2D locus.
AB  - The mammalian cytochrome P450-dependent monooxygenase system is involved in the
      metabolism of drugs and chemical carcinogens. The role of these enzymes in
      toxicological response is exemplified by an autosomal recessive polymorphism at
      the cytochrome P450 CYP2D6 debrisoquine hydroxylase locus which results in the
      severely compromised metabolism of at least 25 drugs, and which in some cases can
      lead to life-threatening side-effects. In addition, this polymorphism, which
      affects 8-10% of the caucasian population, has been associated with altered
      susceptibility to lung and bladder cancer. Here we report the identification of
      the primary mutation responsible for this metabolic defect and the development of
      a simple DNA-based genetic assay to allow both the identification of most
      individuals at risk of drug side-effects and clarification of the conflicting
      reports on the association of this polymorphism with cancer susceptibility.

PMID- 1978252
TI  - Should camp-followers be policemen?

PMID- 1978253
TI  - Interconversion of CD45R subsets of CD4 T cells in vivo.
AB  - T lymphocytes express multiple forms of the leukocyte common antigen CD45,
      transcribed by alternative usage of leukocyte-common antigen exons 4-6. Species
      specific monoclonal antibodies against restricted epitopes (CD45R) of the antigen
      subdivide CD4 T cells into reciprocal subsets expressing either the high
      molecular weight isoforms CD45RA or RB or a molecule in which exons 4-6 have been
      spliced out (CD45R0). CD45R+ or RB+ CD4 T cells are potent in graft-versus-host
      reactions, and interleukin-2 related activities, whereas the CD45R0+ subset
      responds in vitro to recall antigens and provides help for antibody synthesis. It
      is unclear whether CD45R subsets derive from separate lineages, or are products
      of unidirectional or reversible differentiation. We show by transferring CD45R+
      or CD45R- allotype-marked CD4 T cells into athymic nude rats that both subsets
      routinely generate cells of the opposite phenotype with a function that follows
      phenotype, not parentage. The recent equation of CD45R subsets as maturation
      stages representing 'naive' and 'memory' T cells is difficult to reconcile with
      this finding.

PMID- 1978254
TI  - Calcium channels. Gating for the physiologist.

PMID- 1978255
TI  - [Phenylketonuria as a model system for DNA diagnosis of hereditary disorders].
AB  - Phenylketonuria (PKU), due to a defect in phenylalanine hydroxylase (PAH), is
      presented as a model system for computer-aided DNA diagnosis of genetic diseases.
      Eight different restriction fragment length polymorphism (RFLP) markers have been
      localized within the introns of the 90 kb PAH gene (located on chromosome 12).
      These RFLPs can be combined in 384 different ways and each combination has been
      defined as a particular haplotype. A special computer program has been developed
      to calculate the possible haplotype combinations in a PKU core family (index
      patient and parents), with the goal to derive unambiguously both the PAH and PKU
      alleles. Taking into account that participation of other members of the family
      (grandparents or brothers/sisters) is sometimes necessary, haplotyping by itself
      is sufficient to establish (or exclude) the PKU status of an individual in
      approximately eight out of ten PKU families.

PMID- 1978256
TI  - A chloride activated alanine aminopeptidase from a melanoma cell line.
AB  - Alanine aminopeptidase was partially purified from cultured human melanoma cells
      (Bowes) by gel filtration on Sephadex G-200 and DEAE Sepharose column
      chromatography. The molecular weight of the enzyme was about 52,000 as determined
      by gel filtration on Sephadex G-100. The enzyme hydrolyzed L-alanine beta
      naphthylamide (NA), but not or slightly L-methionine-NA, L-leucine-NA, and L
      arginine-NA. The Km value for L-alanine-NA was 0.17 mmol/l, pH optimum was 7.4.
      The enzyme was stable at 50 degrees C for 20 min, but lost about 50% of its
      activity at 60 degrees C within 20 min. It was markedly stimulated by chloride
      ions, and was inhibited by sulfhydryl blocking agents and EDTA. The activity was
      restored by the addition of Co2+ or Zn2+ after EDTA treatment. The enzyme is a
      metallo- and thiol-dependent and chloride-activated, low-molecular weight
      aminopeptidase.

PMID- 1978257
TI  - [Hemodilution in stroke. Satellite symposium to the First International European
      Stroke Conference. Dusseldorf, 12-13 May 1990. Proceedings].

PMID- 1978258
TI  - "Upstream" regulation of the release probability in sympathetic nerve
      varicosities.
AB  - The results appear to support the following tentative working hypothesis. (1)
      Nerve impulse-induced transmitter release from sympathetic nerve varicosities is
      monoquantal and highly intermittent (probability range: 0-0.03). (2) Nerve
      impulses invade varicosities as all-or-none, Na+ channel-dependent action
      potentials; invasion failure may be rare. (3) The release probability is not
      controlled by properties (amplitude or duration) of the invading action potential
      or the resulting Ca2+ current, but by the availability of an as yet unidentified
      permissive factor. (4) The permissive factor is actively transported intra
      axonally, probably in association with organelles (LDVs?). (5) The activation
      and/or transport of the permissive factor are controlled "upstream" of the
      varicosity; they depend on Ca2+ influx through channels insensitive to nifedipine
      (hence, not of L-type) but blocked by Cd2+ and apparently opened by slight
      depolarization of the resting membrane, in this respect behaving more as T- than
      N-type channels. (6) A high resting K+ efflux "upstream" of the varicosity
      restricts the availability of the permissive factor; it is the main mechanism
      maintaining the (economically necessary) low release probability. (7)
      Prejunctional agonists do not inhibit transmitter secretion by causing a
      conduction block or by reducing the action potential-induced Ca2+ influx into the
      varicosity itself, but by depressing the Ca2(+)-dependent activation and/or
      transport of the permissive factor; they act at least in part via receptors
      "upstream" of the varicosity. (8) This hypothesis for regulation of the release
      probability in sympathetic nerves may apply, at least in part, to other neurons
      as well.

PMID- 1978259
TI  - Involvement of N-methyl-D-aspartate receptors in nociception and motor control in
      the spinal cord of the mouse: behavioral, pharmacological and
      electrophysiological evidence.
AB  - The present study evaluated, using behavioral and electrophysiological methods,
      the involvement of the N-methyl-D-aspartate receptor in the processing of noxious
      information in the spinal cord of the mouse. The selectivity of the excitatory
      amino acid antagonists 2-amino-5-phosphonovalerate and
      glutamylaminomethylsulphonate was assessed behaviorally, using their ability to
      reverse the biting behavior elicited by intrathecal excitatory amino acid
      administration as a tool. 2-Amino-5-phosphonovalerate at concentrations up to 1
      mM was shown to be selective for the N-methyl-D-aspartate receptor, while
      glutamylaminomethylsulphonate was selective for the kainate and quisqualate
      receptors at similar concentrations. At these concentrations, intrathecal
      administration of 2-amino-5-phosphonovalerate to awake mice produced significant
      analgesia on a battery of tests, as well as a dose-related motor impairment,
      while glutamylaminomethylsulphonate was without effect. Proof that 2-amino-5
      phosphonovalerate exerts its effects via N-methyl-D-aspartate receptors is that
      glutamylaminomethylsulphonate, at concentrations which also block this receptor
      (greater than 1 mM), also produced analgesia and motor effects. Furthermore, N
      methyl-D-aspartate, but not kainate or quisqualate, reversed the analgesic
      effects of 2-amino-5-phosphonovalerate. In fact, significant potentiation of
      analgesia could be seen with quisqualate. In accordance with the behavioral
      pharmacological data, topical application of 2-amino-5-phosphonovalerate onto the
      spinal cord of anesthetized mice significantly depressed the response of spinal
      sensory neurons to noxious mechanical and electrical stimulation, but did not
      affect the activity of neurons which showed no preferential reaction to noxious
      stimulation. Glutamylaminomethylsulphonate at non-analgesic concentrations was
      without effect. Based on these and other studies we conclude that N-methyl-D
      aspartate receptor bearing interneurons participate in nociception, and that N
      methyl-D-aspartate antagonists exert their analgesic and motor effect by changing
      the tone of spinal neural action in the spinal cord, rather than direct
      intervention in primary afferent transmission.

PMID- 1978260
TI  - Catecholaminergic systems in the medulla oblongata in parkinsonian syndromes: a
      quantitative immunohistochemical study in Parkinson's disease, progressive
      supranuclear palsy, and striatonigral degeneration.
AB  - We investigated tyrosine-hydroxylase (TH)-immunoreactive neurons in the medulla
      oblongata corresponding to the A1 and A2 cell groups in autopsy tissue of
      patients with Parkinson's disease (PD) (n = 3), progressive supranuclear palsy
      (PSP) (n = 3), striatonigral degeneration (SND) (n = 2), and in controls (n = 4).
      The estimated total number of TH-positive neurons in the A1 and the A2 regions
      was normal in PD and PSP patients. The sparing of medullary catecholaminergic
      cells in PD and PSP may be related to their minor degree of melanization and the
      possibility that intermediate compounds associated with the oxidative catabolism
      of norepinephrine and epinephrine may be less cytotoxic than those generated by
      degradation of dopamine. Patients with SND showed a marked loss of TH
      immunoreactive cells in the A1 and the A2 groups, which may contribute to the
      impairment of vasomotor control characteristic of the disease.

PMID- 1978261
TI  - A comparison of regulatory cells in spinal fluid and blood in patients with
      multiple sclerosis and other neurologic diseases.
AB  - Multiple sclerosis is a disease in which immune abnormalities are present both in
      the CNS and peripheral blood. Whether these changes are primary or secondary to
      the disease process is not known. We tested T-cell clones derived from activated
      lymphocytes in the blood and CSF of MS patients and controls for their capacity
      to regulate T-cell responses to alloantigens. A wide spectrum of regulatory
      functions were observed, ranging from marked enhancement to almost complete
      suppression. Clones from different patient populations and anatomic sites were
      equivalent in their regulatory functions with the net effect of clones in each
      compartment being suppression. However, certain clones from CSF and peripheral
      blood had the capacity to stimulate autologous T cells. Percentages of such
      clones in the peripheral blood of MS patients were significantly higher than in
      controls, while percentages in MS and other neurologic diseases (OND) CSF were
      equivalent. Our data suggest that (1) functional suppressor cells are not lost
      from the blood or CSF or MS and OND patients, (2) lymphocytes that have entered
      the CNS in patients with MS and other CNS diseases have equivalent regulatory
      functions, (3) MS may be an illness in which peripheral immunologic events are
      important in perpetuating the disease process, and (4) responses to autologous
      antigens may also play a role in this perpetuation.

PMID- 1978262
TI  - [Aortic valve replacement in a case of Takayasu's disease with polydistributed
      localization].
AB  - We report a case of a 49 year-old woman suffering from severe aortic
      regurgitation due to Takayasu's disease involving the ascending and abdominal
      aorta and the brachial arteries. The patient was managed successfully with aortic
      valve replacement. Considering the Literature data, the pathogenesis of the
      aortic insufficiency and the main surgical and anaesthesiologic problems related
      to the Takayasu's disease are discussed.

PMID- 1978263
TI  - Evidence that glutamate is the transmitter mediating respiratory drive from
      medullary premotor neurons to phrenic motoneurons: a double labeling study in the
      rat.
AB  - Glutamate immunoreactivity was found in 81-84% of the bulbospinal neurons
      projecting to the phrenic motoneuron pool, which were located in the para
      ambiguous nucleus and the ventral vicinity of the retrofacial nucleus. Their
      glutamate contents were identified by a double labeling technique in combination
      with the retrograde transport of horseradish peroxidase and immunocytochemistry
      of the glutamate. The remaining 16-19% of the bulbospinal neurons projecting to
      the phrenic motoneuron pool did not contain glutamate immunoreactivity. Thus it
      appears that glutamate may be a major transmitter of the inspiratory drive from
      the medullary respiratory neurons to the phrenic motoneurons.

PMID- 1978264
TI  - Applicability of Pascal distribution to quantal analysis for non-stationary
      release of neurotransmitter.
AB  - In order to assess the applicability of theoretical distributions to statistical
      analysis of neurotransmitter release, we made mathematical approaches such as
      derivation of frequency-generating function of the distributions, and obtained a
      result that a frequency distribution of the number of quanta released by the
      consecutive stimulations is described by a Pascal distribution when the Poisson
      parameter m varies temporally according to a gamma (gamma) distribution.
      Therefore, if the experimentally obtained distribution fits with a Pascal
      distribution, this suggests that non-stationary nature of the release mechanism.

PMID- 1978265
TI  - Bilateral regulation of glutamate tissue and extracellular levels in caudate
      putamen by midbrain dopamine neurons.
AB  - Tissue levels and in vivo release of glutamate were measured in caudate-putamen
      of rat brain after a unilateral 6-hydroxydopamine lesion of meso-striatal/meso
      cortico-limbic dopamine neurons. The results were compared with glutamate levels
      from corresponding regions in sham-injected animals. The unilateral dopamine
      lesion induced a bilateral increase of tissue levels of glutamate (45%
      ipsilateral and 39% contralateral to the lesion). Extracellular levels of
      glutamate as measured by microdialysis were also bilaterally increased (107%
      ipsilateral and 94% contralateral to the lesion). The results indicate that
      mesencephalic dopamine neurons regulate neuronal glutamate in ipsilateral as well
      as contralateral caudate-putamen.

PMID- 1978266
TI  - Magnesium removal induces paroxysmal neuronal firing and NMDA receptor-mediated
      neuronal degeneration in cortical cultures.
AB  - Removal of extracellular Mg2+ triggered the onset of repetitive excitatory
      discharges in cultured murine cortical neurons, detected by recording with patch
      electrodes in the whole cell configuration. The discharges were suppressed by 100
      microM D-2-amino-5-phosphonovalerate. Over the next 24-72 h substantial numbers
      of neurons, but not glia, degenerated, releasing lactate dehydrogenase to the
      bathing medium. The neuronal death induced by removal of extracellular Mg2+ could
      be attenuated by either 3 microM tetrodotoxin or 50 microM dextrorphan, and thus
      likely reflects excessive activation of N-methyl-D-aspartate receptors triggered
      by excitatory discharges. This Mg2+ removal model may be a useful model in which
      to study certain aspects of epileptic neocortical injury.

PMID- 1978267
TI  - Chronic methionine sulfoximine administration reduces synaptosomal aspartate and
      glutamate in rat striatum.
AB  - Methionine sulfoxime (MS) is an inhibitor of glutamine synthetase, an astroglial
      enzyme believed to be involved in the maintenance of glutamine, a major precursor
      for neurotransmitter pools of the excitatory amino acids aspartate and glutamate
      in striatal afferent axon terminals. MS was infused for 7 days (24
      micrograms/day) into the lateral cerebral ventricle of rats. On the side of MS
      infusion, there was a decrease of striatal synaptosomal aspartate (61%),
      glutamine (63%), and glutamate (48%), while taurine and gamma-aminobutyrate were
      unaltered when compared to vehicle-treated rats. The results indicate that
      chronic MS infusion is an effective means by which neurotransmitter aspartate and
      glutamate levels can be selectively reduced in the striatum.

PMID- 1978268
TI  - Abstracts of the fourth meeting of the Italian Society of Neuroscience. Palermo,
      Italy, 4-7 December 1990.

PMID- 1978269
TI  - Neurotoxicology and risk assessment. Seventh International Neurotoxicology
      Conference. Little Rock, Arkansas, September 18-21, 1989. Proceedings.

PMID- 1978270
TI  - Qualitative and quantitative comparability of human and animal developmental
      neurotoxicants: a workshop summary.
AB  - A Workshop on the Qualitative and Quantitative Comparability of Human and Animal
      Developmental Neurotoxicity was held in Williamsburg, Va. on April 11-13, 1989.
      Based upon data presented at the Workshop, the degree of qualitative and
      quantitative comparability between data obtained from humans and experimental
      animals is reviewed for several developmental neurotoxicants (lead, agents of
      abuse, alcohol, PCBs, phenytoin, methylmercury, and ionizing radiation).
      Qualitative comparability was considered for the following functional categories:
      motor development and function, cognitive function, sensory function,
      motivation/arousal behavior, and social behavior. Quantitative comparability was
      assessed by comparing administered dose as well as measures of internal dose
      (e.g., blood levels) for selected agents. Comparability of qualitative changes
      between humans and rodents was most apparent when comparisons were made on the
      basis of general categories of behavioral function. These data support the use of
      animal models in assessing risk for developmental neurotoxicants and provide
      guidance on the types of functional end points that can be incorporated into a
      developmental neurotoxicity testing battery. Evidence of quantitative
      comparability was most apparent when an internal measure of dose (e.g., blood
      level) was used.

PMID- 1978271
TI  - Neurochemical basis of neurotoxicity.
AB  - The neurotoxic properties of 6-hydroxydopamine and 5,7-dihydroxytryptamine are
      reviewed. The neurochemical responses of the dopaminergic and serotonergic
      systems after methamphetamine (METH) are reported. METH decreased activities of
      tyrosine hydroxylase and tryptophan hydroxylase; concentrations of dopamine (DA)
      and 5-hydroxytryptamine (5HT) and their respective metabolites were decreased in
      parallel with the decline in activity of the enzymes. When a variety of
      pharmacologic or surgical procedures were used to decrease DA content prior to
      administration of METH, the effects of METH were attenuated. From these data it
      is inferred that DA is essential for the METH-induced response. 3,4
      Methylenedioxymethamphetamine (MDMA) produced similar effects which were also DA
      dependent. Evidence for a role of glutamate and oxidative stress in the
      neurotoxicity of the amphetamines is presented.

PMID- 1978272
TI  - Postgraduate internship in gynecology and obstetrics for physician assistants: a
      4-year experience.
AB  - Changes in the Hospital Code (405 Regulations) to limit the number of hours
      worked by residents have been implemented in New York state and may soon become a
      nation-wide policy. Although their goal is to guarantee quality of patient care
      and assure education for residents, the limitation of hours worked has increased
      manpower shortages, some of which could be resolved by using physician assistants
      with specialty training. To provide this training, a Postgraduate Internship in
      Gynecology and Obstetrics for Physician Assistants has been developed at the
      North Central Bronx Hospital and the Montefiore Medical Center. It is the first
      program of its kind at the postgraduate level to educate physician assistants
      specifically for practice in obstetrics and gynecology. The program consists of 3
      months of didactic lectures to review and update knowledge on topics in medicine,
      surgery, gynecology, preoperative and postoperative care, cardiac and trauma life
      support, and critical care, followed by a clinical year similar to that of a
      rotating physician intern. We believe that such postgraduate educational
      opportunities in gynecology and obstetrics benefit both the individual physician
      assistant's growth and development and the level of care delivered, and may be an
      answer to staffing needs.

PMID- 1978273
TI  - [40th scientific congress of the Federal Association of Physicians in Public
      Health Service. May 7-10, 1990, Freiburg].

PMID- 1978274
TI  - [Metastatic C-cell carcinoma with bone marrow carcinosis in type IIa multiple
      endocrine neoplasia (MEN). Diagnostic and therapeutic problems].
AB  - The course of the disease in a patient with multiple endocrine neoplasia type IIa
      over a period of seven years is described. In spite of multiple diagnostic
      procedures, only a bone marrow biopsy was able to prove metastatic disease. All
      therapeutic measures, such as combination chemotherapy, sandostatin,
      bromocriptine, and 131Iodinemethylendiphosphonate-therapy were not effective in
      reducing tumor load or symptoms.

PMID- 1978276
TI  - 'Non-cardiogenic pulmonary edema after narcotic treatment for cancer pain,' by
      Bruera and Miller (Pain, 39 (1989) 297-300)

PMID- 1978275
TI  - Effects of dapiprazole on the reversal of pharmacologically induced mydriasis.
AB  - The ability of a new alpha-adrenergic antagonist, dapiprazole, to reverse
      mydriasis produced by phenylephrine 2.5% or 10%, tropicamide 0.5%, and the
      combination of phenylephrine 2.5% and tropicamide 0.5% was investigated. A double
      masked crossover design was used to study both efficacy of mydriatic reversal and
      time course. The safety of administration was evaluated as well. Subjects were
      optometry students and their spouses. The results demonstrate that dapiprazole is
      safe and effective for reversing mydriasis produced by both concentrations of
      phenylephrine, and partially effective in reversing mydriasis in eyes treated
      with tropicamide 0.5%, alone, or in combination with 2.5% phenylephrine.

PMID- 1978277
TI  - Comparison of the influence of rostral and caudal raphe neurons on the adrenal
      secretion of catecholamines and on the release of adrenocorticotropin in the cat.
AB  - Neuroendocrine and autonomic responses were assessed in chloralose-anesthetized
      cats after chemical stimulation of medial brain-stem regions, including those
      that influence nociceptive input to the medullary or spinal dorsal horn.
      Microinjections of L-glutamate (0.5 M, 160 nl) were directed at the following
      rostral and caudal raphe nuclei: the periaqueductal gray (PAG), the dorsal raphe
      nucleus (DR), the raphe magnus (RM), and the raphe obscurus/raphe pallidus
      (Ro/Rpa). Activation of DR neurons evoked a significant increase in the adrenal
      secretion of epinephrine (+2.6 +/- 1.1 ng/min, P less than 0.01) that returned
      towards prestimulus values by 6 min, whereas microinjections into other raphe
      nuclei had no consistent effect. Activation of Ro/Rpa neurons evoked an increase
      in the plasma concentration of adrenocorticotropin (ACTH, +47.9 +/- 12.3 pg/ml, P
      less than 0.01), whereas microinjections into other raphe nuclei did not affect
      ACTH. Arterial pressure increased significantly after activation of PAG (+7.5 +/-
      2.1 mm Hg, P less than 0.01) or of DR (+4.8 +/- 2.0 mm Hg, P less than 0.05)
      neurons, whereas heart rate increased significantly (P less than 0.05) after
      stimulation of cells within the Ro/Rpa. Glutamate microinjections within the RM,
      a raphe nucleus that exerts a significant descending influence on nociceptive
      input to the medullary and to the spinal dorsal horns, had no consistent effect
      on any measured variable. No evidence was seen to suggest that chemical
      activation of neurons within raphe nuclei inhibited the adrenal secretion of
      catecholamines or inhibited the release of ACTH. The results indicated that
      glutamate activation of neurons within different raphe nuclei evoked non-uniform
      effects on neuroendocrine and autonomic function. Further, these data suggested
      that the neural substrate underlying the control of the adrenal secretion of
      catecholamines and of the release of ACTH in response to activation of raphe
      neurons is likely distinct from that which contributes to the descending
      influence on nociceptive input to the medullary and spinal dorsal horn.

PMID- 1978278
TI  - [Mechanism of action of beta-blockers].
AB  - If beta-blockage does not cause lowering of aqueous humor secretion, in itself
      responsible for the maintenance of intraocular pressure, what is the mechanism of
      action? The antagonism for indolamines, recently measured in aqueous humor, the
      absence of nocturnal effect, and the amplitude diminution of diurnal variations
      thus produced suggest that beta-blockers could interact with indolamines, since
      the latter are probably responsible for intraocular pressure regulation. Aqueous
      humor secretion depends to a major extent on the sodium-potassium pump and its
      enzyme, Na+K(+)-ATPase. Serotonin, known for its activating action on Na+K(+)
      ATPase, is present in the greatest amounts in the morning, precisely when the
      aqueous humor secretion is the highest. Moreover, timolol is a potent antagonist
      of serotonin, suggesting that beta-blockers could decrease the secretion by
      antagonism with serotonin at the level of Na+K(+)-ATPase. Since serotonin is
      metabolized to melatonin during sleep, beta-blockers might simulate a state of
      sleep of the ciliary epithelium.

PMID- 1978279
TI  - Symposium on Perinatal Infectious Diseases: Update, 1990. Proceedings.

PMID- 1978280
TI  - Ribavirin therapy for respiratory syncytial virus infections. A scientific
      workshop. Long Beach, California, September 26-27, 1989. Proceedings.

PMID- 1978281
TI  - Stimulation of a bulbospinal 5-HT pathway in the rat brain produces
      hyperglycaemia.
AB  - The glucoregulatory role of spinally projecting serotonin (5-HT) neurones near
      the ventrolateral surface of the medulla oblongata was investigated by
      stimulating these nerve cells in normal rats and in rats with selective chemical
      ablation of 5-HT nerves in the spinal cord. Electrical stimulation of the lateral
      medulla produced hyperglycaemia in normal rats; the increase in blood glucose was
      proportional to the intensity and frequency of stimulation. Furthermore,
      microinjection of kainic acid or L-glutamate at the same sites also produced
      hyperglycaemia. This stimulation-induced hyperglycaemia was significantly reduced
      by spinal transection or adrenalectomy. Selective destruction of spinal 5-HT
      nerves produced by intraspinal injection of 5,7-dihydroxytryptamine also reduced
      the magnitude of the hyperglycaemia response to electrical stimulation of the
      lateral medulla. This indicates that stimulation of 5-HT nerve cells adjacent to
      the ventrolateral surface of the medulla oblongata and projecting to the spinal
      cord increases the adrenal-sympathetic efferent activity and leads to
      hyperglycaemia in rats.

PMID- 1978282
TI  - Homeobox containing genes in the nematode Caenorhabditis elegans.
AB  - We designed a unique 36-mer oligonucleotide probe, based on the most highly
      conserved amino acid sequences of Antennapedia-like homeodomains and the codon
      bias of Caenorhabditis elegans. This probe was then used to isolate four classes
      of genes from a C. elegans genomic library. Sequencing reveals that we have
      isolated three new homeobox genes, designated ceh-1, ceh-9 and ceh-10. The fourth
      homeobox gene, ceh-11, has recently been described by Schaller et al (Nucleic
      Acids Res. 18, 2033-2036). The amino acid sequence of ceh-1 is 87% similar to the
      honeybee H40 homeodomain, 85% similar to the Drosophila NK-1 homeodomain and 82%
      similar to the chicken CHox3 homeodomain. The sequence ceh-10 appears to be a
      member of the paired class of homeodomains. The other two sequences, ceh-9 and
      ceh-11, remain unclassified. Three of the four sequences have at least one intron
      within the homeobox region. Transcripts of ceh-10 and ceh-11 are present in
      embryonic RNA but are greatly diminished in later developmental stages. Three of
      the four new genes have been placed on the C. elegans genomic map.

PMID- 1978283
TI  - SacI RFLPs at the D8S51 locus.

PMID- 1978284
TI  - Two polymorphisms in the non-coding regions of the BCHE gene.

PMID- 1978285
TI  - Three RFLPs at the D8S49 locus.

PMID- 1978286
TI  - A polymorphism of the MYH7 gene.

PMID- 1978287
TI  - Asp700 RFLP at the D8S45 locus.

PMID- 1978288
TI  - Two polymorphisms of the FOS oncogene.

PMID- 1978289
TI  - Two EcoRI RFLPs at the GLUT2 locus.

PMID- 1978290
TI  - Two RFLPs at the D8S42 locus.

PMID- 1978291
TI  - A myeloperoxidase cDNA clone identifies an EcoRV RFLP.

PMID- 1978292
TI  - A TaqI RFLP at the EDN1 gene locus.

PMID- 1978293
TI  - An EcoRI RFLP at the D10S103 locus.

PMID- 1978294
TI  - SacI polymorphism in the RRM1 gene.

PMID- 1978295
TI  - D21S170 maps to terminal 21q22.3.

PMID- 1978296
TI  - HindIII restriction fragment alleles of the human immunoglobulin V lambda II
      subgroup genes.

PMID- 1978297
TI  - BgIII RFLP at the HOX1I locus.

PMID- 1978298
TI  - HindIII RFLP of the human immunoglobulin V lambda III subgroup genes.

PMID- 1978299
TI  - A monoclonal antibody to somatostatin with potent in vivo immunoneutralizing
      activity.
AB  - The spleen from a Robertsonian mouse with high titer and affinity antiserum after
      being immunized with somatostatin-14 conjugated to keyhole limpet hemocyanin was
      fused with FOX-NY cells. Hybridomas were cloned by limiting dilution, subcloned,
      and ascites was produced from the highest affinity close in pristine-primed
      Balb/c mice. Ascites fluid contained approximately 20 mg/ml IgG and bound 50% of
      1 fmol 125I-[Tyr1]-somatostatin at a final dilution of 1:10,000,000. Binding of
      this IgG1 antibody, CURE.S6, was inhibited by 50% at 40 pM concentrations of
      either somatostatin-14 or somatostatin-28, but was not inhibited by [D-Trp8 
      somatostatin at 1000-fold higher concentrations. The antibody produced very
      intense specific immunohistochemical staining of somatostatin endocrine cells in
      the stomach and pancreas and of intestinal somatostatin neurons with extremely
      low background staining. Intravenous injection of 2 mg purified antibody in
      urethane-anesthetized rats resulted in 300-fold increase in plasma GH within 15
      min. CURE.S6 is a high affinity monoclonal antibody directed at the biologically
      active somatostatin ring structure. This antibody is useful for in vivo
      immunoneutralization of exogenous and endogenous somatostatin in the rat and also
      is an excellent reagent for immunohistochemical localization of somatostatin.

PMID- 1978300
TI  - Dynorphin increases in the dorsal spinal cord in rats with a painful peripheral
      neuropathy.
AB  - It is known that painful tissue injury evokes an increase in dynorphin in spinal
      neurons. It is not known, however, whether dynorphinergic systems respond
      similarly to the pain that accompanies peripheral neuropathy. Radioimmunoassays
      and immunocytochemistry were used to evaluate changes in dynorphin A(1-8) in the
      spinal cord of rats with a painful peripheral neuropathy. The neuropathy is the
      result of a constriction injury that is created by tying loose ligatures around
      the common sciatic nerve. Signs of abnormal pain sensations, hyperalgesia,
      allodynia (pain after normally innocuous stimuli), and spontaneous pain (or
      dysesthesia), are first detected 2-5 days after injury, reach peak severity in
      about 10 days, and persist for 2-3 months (Bennett, G. J.; Xie, Y.-K. Pain 33:87
      107; 1988). Dynorphin increased by 5 days in cells in laminae I-II and V-VII in
      the lumbar spinal cord ipsilateral to the injury. This increase, maximal at 10
      days (262%), was still present 20 days after the injury but was now seen only in
      neurons in the deep laminae (V-VII). Thus, the spinal dynorphinergic system
      appears to respond to neuropathic pain. Furthermore, our results suggest that
      dynorphinergic cells in the superficial and deep laminae may have different roles
      in nociception.

PMID- 1978301
TI  - Flutamide has no effect on adrenal androgen response to acute ACTH stimulation in
      patients with prostatic cancer.
AB  - Basal levels and adrenocorticotropic hormone (ACTH)-induced increments (delta
      values) of serum cortisol, dehydroepiandrosterone (DHA), dehydroepiandrosterone
      sulfate (DHAS), 4-androstene-3, 17-dione (A4), and 17-hydroxyprogesterone
      (170HP); basal testosterone (T), luteinizing hormone (LH), serum ASAT, gamma-GT,
      and albumin were measured in prostatic cancer patients before and after 6 months
      of treatment with LH-RH-agonist, with flutamide, and with LH-RH-agonist +
      flutamide, respectively. Basal DHA and DHAS were decreased during flutamide and
      LH-RH-agonist + flutamide treatment and basal A4 during treatment with LH-RH
      agonist and with LH-RH-agonist + flutamide. Basal 170HP, T, and LH decreased
      during LH-RH-agonist and LH-RH-agonist + flutamide treatment and increased during
      single drug flutamide treatment. Slightly decreased delta cortisol values were
      observed during LH-RH-agonist and during flutamide treatment and slightly
      increased delta 170HP values during LH-RH-agonist and LH-RH-agonist + flutamide
      treatment. Values for delta DHA and delta A4 were completely unaffected by any of
      the treatment regimens. Elevated ASAT values were observed during treatment with
      flutamide and with LH-RH-agonist + flutamide. It is concluded that flutamide has
      no effect on the adrenal androgen response to acute ACTH stimulation.

PMID- 1978302
TI  - Expression of Lewis(x) and Lewis(y) blood group related antigens in fetal livers.
AB  - Aberrant expression of blood group antigens has been observed in human cancers.
      Lewis(x) (Le(x)) and Lewis(y) (Le(y)) antigens are usually absent from
      parenchymal cells in the adult human liver, but frequently expressed on
      cholangiocarcinomas and less frequently on hepatocellular carcinomas. Little
      information is available on the distribution of these antigens in fetal livers.
      We studied five livers each from the first, second, and third trimesters, and
      infants by an immunohistochemical method on paraffin-embedded sections, using
      monoclonal antibodies to Lex and Le(x) antigens. Le(x) was seen in the bile duct
      epithelium of four out of five second and four of five third trimester fetal
      livers and in all the neonatal livers. Hepatocytes and bile duct epithelium of
      first trimester livers were negative. Le(y) staining of bile duct epithelium was
      present in all second and third trimester fetal livers and infant livers.
      Staining of hepatocytes was seen in four of five first, three of five second, two
      of five third trimester livers, and one of five infant livers. These observations
      suggest that the expression of Le(x) on hepatocytes decreases with gestational
      age and that the frequency of Le(x) and Le(y) expression in cholangio- and
      hepatocellular carcinomas follows that of fetal livers.

PMID- 1978303
TI  - Solving panic disorder problems. When your patients' fears thwart their lives.
AB  - All in all, panic disorder with or without agoraphobia is a very satisfying
      illness to treat. Most patients enter treatment with considerable pain and
      disability and within a few weeks to months are free of panic attacks, no longer
      fearful of them, and no longer phobic. Panic disorder must be distinguished from
      generalized anxiety, and signs of agoraphobia must be sought during the initial
      diagnosis. Drug therapy is effective for panic disorder, while agoraphobia may
      respond to drug therapy or to a range of cognitive therapies.

PMID- 1978304
TI  - Is serum gamma-glutamyl transferase a good marker of alcohol intake in stroke
      patients?
AB  - Serial serum gamma-glutamyl transferase (GGT) levels were estimated in 23
      consecutive patients admitted to hospital with a diagnosis of acute stroke. The
      proportion of patients with elevated GGT levels in the initial, 36-hour and 72
      hour samples was 13%, 30% and 24% respectively, suggesting a transient rise
      following a stroke. Patients with a history of diabetes mellitus had an initial
      serum GGT level 21 IU/l (95% confidence interval 6 to 37) higher than non
      diabetics. We conclude that GGT levels after a stroke may reflect a history of
      diabetes and cerebral damage as well as the usual more established causes.
      Physicians, therefore, should be wary of attributing all unexplained high GGT
      levels in stroke patients to alcohol.

PMID- 1978305
TI  - Analysis of restriction fragment length polymorphisms of the major
      histocompatibility complex of 15I5-B-congenic chicken lines.
AB  - Eight 15I5 B-congenic White Leghorn chicken lines, containing haplotypes B2, B5,
      B12, B13, B15, B19, and B21, were subjected to molecular genotyping with chicken
      B-F (Class I) and B-L (Class II) major histocompatibility complex (MHC) probes.
      Genomic DNA was digested with restriction enzymes, hybridized with a Class I or
      Class II probe, and analyzed for restriction fragment length polymorphisms.
      Digestion with HindIII or EcoRI yielded no B-L polymorphisms. Digestion with
      PvuII or BglII and hybridization with a B-L or B-F probe produced polymorphisms
      that were shared between several haplotypes, although the haplotypes with similar
      patterns were clustered differently between Class I and Class II probes. The
      genetic variation seen for B-L and B-F probe hybridization of PvuII digests was
      much less than that previously demonstrated for B-G probing of PvuII digests of
      the same lines. Description of MHC Class I and II restriction patterns of the
      well-characterized 15I5 B-congenic lines will aid in identification of genes
      important in disease resistance.

PMID- 1978306
TI  - Transdermal delivery of narcotic analgesics: pH, anatomical, and subject
      influences on cutaneous permeability of fentanyl and sufentanil.
AB  - The permeation of fentanyl and sufentanil through cadaver skin membranes was
      investigated using in vitro diffusion cell techniques. Neither drug influenced
      the permeation of the other when they were concurrently applied to the skin
      membrane. With respect to transdermal delivery, short diffusion lag times of less
      than 0.5 hr were observed for each compound. Their permeation rates through heat
      isolated epidermis and dermatomed (200- to 250-microns) skin sections were
      essentially the same. However, when the stratum corneum was removed by tape
      stripping, the respective permeability coefficients were increased greater than
      30-fold, establishing the stratum corneum as the principal barrier to their skin
      permeation. Permeation was also studied as a function of pH. From pH 4 to pH 8
      the permeability coefficients of both fentanyl and sufentanil, calculated from
      the total solution concentration regardless of ionization, increased
      exponentially. The free base is thus responsible for the relatively facile skin
      permeation of these drugs. Factoring of the independent permeability coefficients
      of the ionized and free-base forms was possible, with the latter being over two
      log orders larger than seen for the protonated species. Permeability coefficients
      of fentanyl and sufentanil through skin sections obtained from different cadavers
      varied four- to fivefold. Neither gender nor age was a flux-determining variable
      for either drug. The permeability coefficients of the drugs through skin sites as
      diverse as the sole of the foot, chest, thigh, and abdomen were remarkably
      similar. Their fluxes were sufficient for transdermal administration.

PMID- 1978307
TI  - [Epidemiology of hemorrhagic fever with renal syndrome in the Ardennes region].

PMID- 1978308
TI  - [Acute kidney failure after ingestion of floctafenine. Role of concomitant
      alcohol consumption].

PMID- 1978309
TI  - [Maintenance treatments of rheumatoid arthritis].

PMID- 1978310
TI  - [Beta-blockaders in the treatment of heart failure].

PMID- 1978311
TI  - [34th congress of the German Society for Pneumology and Tuberculosis. Bochum, 19
      22 September 1990. Abstracts].

PMID- 1978312
TI  - [The neuromodulatory role of luliberin in regulating the sexual behavior of the
      male rat].

PMID- 1978313
TI  - [The structure and hormonal regulation of the expression of tyrosine
      aminotransferase genes in mammals].

PMID- 1978315
TI  - Somatostatin inhibits neurally stimulated pancreatic secretion indirectly.
AB  - We studied the effect of a primed i.v. infusion of somatostatin (100 micrograms
      as a bolus, 0.5 micrograms x kg-1 x min-1) on pancreatic exocrine secretion in
      response to electrical stimulation of the vagus nerves and intra-arterial
      infusions of acetylcholine (0.5 mg x min-1) in anesthetized pigs (17-22 kg). In
      control experiments, vagus stimulation and acetylcholine increased protein
      secretion 31- to 80-fold and 106-fold, respectively. Somatostatin inhibited the
      response to vagus stimulation by more than 90%, whereas the response to
      acetylcholine remained unaffected. It is concluded that the inhibitory action of
      somatostatin on the vagally induced secretion must be due to an inhibition of the
      impulse transmission in the efferent parasympathetic nerves to the pancreas, and
      it is suggested that this mechanism contributes to the inhibitory effect of
      somatostatin observed with other stimuli as well.

PMID- 1978314
TI  - Sequential morphological changes in pancreatic islets of spontaneously diabetic
      rats.
AB  - This study describes the sequential morphological changes in pancreatic islets
      from 1-, 6-, and 18-month-old male eSS rats, as compared to aged-matched control
      animals. Spontaneous diabetes mellitus was confirmed in 6- and 18-month-old eSS
      rats after an oral glucose tolerance test. Light microscopic immunocytochemical
      and morphometric techniques were used to study islet-cell populations. The
      pancreas was normal, and the morphometric methods did not reveal significant
      changes in islets from 1-month-old rats. However, 6-month-old eSS animals showed
      disruption of islet architecture and fibrosis in the stroma. The volume density
      (Vvi) of endocrine tissue and the Vvi and percentage of B cells were increased,
      whereas the Vvi of exocrine tissue and the Vvi and percentage of A cells were
      diminished. Eighteen-month-old eSS rats also exhibited conspicuous islet lesions.
      Nevertheless, the Vvi of endocrine tissue and the Vvi and percentage of B cells
      were diminished, while the Vvi of exocrine tissue and the Vvi and percentage of D
      cells were increased. Our results provide further quantitative evidence for the
      sequential morphological events occurring in the pancreatic islets of a useful
      animal model of diabetes mellitus.

PMID- 1978316
TI  - Interleukin 1 induces beta-endorphin secretion via Fos and Jun in AtT-20
      pituitary cells.
AB  - Previous work had shown that interleukin 1 (IL-1), after a long period of
      treatment, stimulates beta-endorphin release and potentiates the effects of
      secretagogues in AtT-20 cells, a mouse anterior pituitary cell line. Treatment of
      AtT-20 cells with IL-1 induced a transient and early stimulation of mRNA
      expression by both immediate-early protooncogenes Fos and Jun (mouse c-fos and c
      jun). The effect appeared within 30 min, and returned to basal levels after 2 hr.
      Desensitization of protein kinase C by phorbol ester pretreatment had no effect
      on the ability of IL-1 to induce Fos and Jun mRNA expression. Somatostatin, an
      inhibitor of cAMP and beta-endorphin secretion, did not reduce the IL-1 effect on
      Fos and Jun mRNA expression. Addition to AtT-20 cells of antisense
      oligonucleotides to Fos and Jun abolished the secretion induced by IL-1. These
      results indicate that immediate-early signals Fos and Jun are involved in IL-1
      induced beta-endorphin secretion in AtT-20 cells.

PMID- 1978317
TI  - Endogenous neurotransmitter activates N-methyl-D-aspartate receptors on
      differentiating neurons in embryonic cortex.
AB  - Before synapses form in embryonic turtle cerebral cortex, an endogenous
      neurotransmitter activates N-methyl-D-aspartate (NMDA) channels on neurons in the
      cortical plate. Throughout cortical development, these channels exhibit voltage
      dependent Mg2+ blockade and are antagonized by D-2-amino-5-phosphonovaleric acid,
      a selective NMDA receptor antagonist. The activation in situ of these nonsynaptic
      NMDA channels demonstrates a potential physiological substrate for control of
      early neuronal differentiation.

PMID- 1978318
TI  - Diastrophic dysplasia gene maps to the distal long arm of chromosome 5.
AB  - We have used polymorphic DNA markers to map the gene for a clinically well
      characterized form of osteochondrodysplasia, diastrophic dysplasia (DD), an
      autosomal recessive disorder of unknown pathogenesis. Linkage was analyzed in 13
      families with two or three affected sibs comprising a total of 84 individuals.
      Positive two-point logarithm-of-odds (lod) scores were obtained between the DD
      locus and three polymorphic markers on chromosome 5. The highest pairwise lod
      score estimate of 7.37 with zero recombination to locus D5S72 suggests very tight
      linkage. There was no evidence of heterogeneity. Multipoint linkage analysis
      against the published order of the three loci gave the result centromere-D5S84
      (DD, D5S72)-D5S61-terminus with a four-point lod score of 9.11. The present
      findings place the DD locus distal to the gene for adenomatous polyposis coli on
      the distal part of the long arm of chromosome 5. Our results provide a basis for
      refining the map position of the DD locus followed by physical localization,
      isolation, and characterization of the gene.

PMID- 1978319
TI  - N-acetylaspartylglutamate: a transmitter candidate for the retinohypothalamic
      tract.
AB  - The retinohypothalamic tract is the neural pathway mediating the photic
      entrainment of circadian rhythms in mammals. Important targets for these retinal
      fibers are the suprachiasmatic nuclei (SCN) of the hypothalamus, which are
      thought to be primary sites for the biological clock. The neurotransmitters that
      operate in this projection system have not yet been determined.
      Immunohistochemistry and radioimmunoassay performed with affinity-purified
      antibodies to N-acetylaspartylglutamate (NAAG) demonstrate that this neuron
      specific dipeptide, which may act as an excitatory neurotransmitter, is localized
      extensively in the retinohypothalamic tract and its target zones, including the
      SCN. Optic nerve transections resulted in significant reductions in NAAG
      immunoreactivity in the optic chiasm and SCN. Analysis of NAAG concentrations in
      micropunches of SCN, by means of radioimmunoassay, showed approximately 50%
      reductions in NAAG levels. These results suggest that this peptide may act as one
      of the neurotransmitters involved in retinohypothalamic communication and
      circadian rhythm entrainment.

PMID- 1978320
TI  - Chimeric phage-bacterial enzymes: a clue to the modular evolution of genes.
AB  - Pneumococcal peptidoglycan amidase (N-acetylmuramoyl-L-alanine amidase, EC
      3.5.1.28) and phage CPL1 lysozyme degrade a common substrate (choline-containing
      pneumococcal cell walls); the former hydrolyzes the bond between muramic acid and
      alanine, whereas the latter breaks down the linkage between muramic acid and
      glucosamine. The amino acid sequences of their C-terminal domains are homologous.
      Chimeric genes were constructed by site-directed mutagenesis: a unique SnaBI
      restriction site in the cpl1 gene, coding for the phage lysozyme, was introduced
      at a location equivalent to the SnaBI site present in the lytA gene, which codes
      for the pneumococcal amidase. The resulting genes expressed lytic activities at
      levels similar to those of the parental genes. The gene products, which have been
      purified to electrophoretical homogeneity, exhibited unusual combined biochemical
      properties--e.g., by exchange of protein domains, we have switched the regulatory
      properties of these enzymes without altering their catalytic activities. Chimeric
      gene construction in Streptococcus pneumoniae and its bacteriophages is an
      excellent model to study the modular organization of genes and proteins and to
      help to establish evolutionary relationships between phage and bacteria. These
      constructions provide an experimental approach to the molecular processes
      involved in cassette recruitment during evolution and contribute support to the
      concept of bacteria as adaptable chimeras.

PMID- 1978321
TI  - Effects of synapsin I and calcium/calmodulin-dependent protein kinase II on
      spontaneous neurotransmitter release in the squid giant synapse.
AB  - The molecular events that control synaptic vesicle availability in chemical
      synaptic junctions have not been fully clarified. Among the protein molecules
      specifically located in presynaptic terminals, synapsin I and calcium/calmodulin
      dependent protein kinase II (CaM kinase II) have been shown to modulate evoked
      transmitter release in the squid giant synapse. In the present study, analysis of
      synaptic noise in this chemical junction was used to determine whether these
      proteins also play a role in the control of spontaneous and enhanced spontaneous
      transmitter release. Injections of dephosphorylated synapsin I into the
      presynaptic terminal reduced the rate of spontaneous and enhanced quantal
      release, whereas injection of phosphorylated synapsin I did not modify such
      release. By contrast CaM kinase II injection increased enhanced miniature release
      without affecting spontaneous miniature frequency. These results support the view
      that dephosphorylated synapsin I "cages" synaptic vesicles while CaM kinase II,
      by phosphorylating synapsin I, "decages" these organelles and increases their
      availability for release without affecting the release mechanism itself.

PMID- 1978322
TI  - Acquisition of protease resistance by prion proteins in scrapie-infected cells
      does not require asparagine-linked glycosylation.
AB  - The scrapie and cellular isoforms of the prion protein (PrPSc and PrPC) differ
      strikingly in a number of their biochemical and metabolic properties. The
      structural features underlying these differences are unknown, but they are
      thought to result from a posttranslational process. Both PrP isoforms contain
      complex type oligosaccharides, raising the possibility that differences in the
      asparagine-linked glycosylation account for the properties that distinguish PrPC
      and PrPSc. ScN2a and ScHaB cells in culture produce several PrP molecules with
      relative molecular masses of 26-35 kDa and proteinase K-resistant cores of 19-29
      kDa. When the cells were treated with tunicamycin, this heterogeneity was
      eliminated and a single PrP species of 26 kDa was observed. Several hours after
      its synthesis, a fraction of this protein became insoluble in detergents and
      acquired a proteinase K-resistant core, thus displaying two of the biochemical
      hallmarks of PrPSc. Synthesis in the presence of tunicamycin restricted the
      proteinase K-resistant cores of PrP to a single species of 19 kDa. No proteinase
      K-resistant PrP was found in uninfected cells. Expression of a mutated PrP gene
      lacking both asparagine-linked glycosylation sites in ScN2a cells resulted in the
      synthesis of 19-kDa proteinase K-resistant PrP molecules. We conclude that
      asparagine-linked glycosylation is not essential for the synthesis of proteinase
      K-resistant PrP and that structural differences unrelated to asparagine-linked
      oligosaccharides must exist between PrPC and PrPSc. Whether unglycosylated PrPSc
      molecules are associated with scrapie prion infectivity remains to be
      established.

PMID- 1978323
TI  - Homeobox gene expression plus autocrine growth factor production elicits myeloid
      leukemia.
AB  - In the murine myelomonocytic leukemia WEHI-3B, proviral insertions have induced
      expression of the Hox-2.4 homeobox gene and the gene for the myeloid growth
      factor interleukin 3 (IL-3). To assess their potential oncogenic role, normal
      bone marrow cells were infected with retroviruses bearing the genes for IL-3 or
      IL-3 plus Hox-2.4. Unlike the IL-3 virus, the IL-3/Hox-2.4 virus was highly
      leukemogenic. Infected cells expressing both genes exhibited retarded
      differentiation in vitro, generated myelomonocytic cell lines, and provoked a
      rapid, transplantable myeloid leukemia in vivo. The oncogenic action of Hox-2.4
      appears to derive from its ability to impede the IL-3-driven terminal
      differentiation of myeloid cells. The results suggest that homeobox genes can
      regulate key differentiation processes such as self-renewal capacity and that
      their inappropriate expression can be oncogenic.

PMID- 1978324
TI  - Analysis of expression of cholecystokinin in dopamine cells in the ventral
      mesencephalon of several species and in humans with schizophrenia.
AB  - The ventral mesencephalons of hamster, guinea pig, cat, monkey, and several
      humans with and without the diagnosis of schizophrenia were analyzed with in situ
      hybridization and immunohistochemistry. Extensive codistribution of
      cholecystokinin mRNA and tyrosine hydroxylase [L-tyrosine, tetrahydropteridine:
      oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2] mRNA was observed in cats
      and monkeys as well as in all five human subjects with the diagnosis of
      schizophrenia and in two out of five control brains. Double labeling revealed
      coexistence of the two markers in cat, monkey, and human. No cholecystokinin mRNA
      or cholecystokinin peptide was detected in the substantia nigra/ventral tegmental
      area of the hamster or guinea pig, even after acute and chronic neuroleptic
      treatment.

PMID- 1978326
TI  - Labeling of epsilon-lysine crosslinking sites in proteins with peptide substrates
      of factor XIIIa and transglutaminase.
AB  - Peptides patterned on the N-terminal sequence of fibronectin were synthesized and
      tested for amine acceptor qualities in reactions with dansylcadaverine catalyzed
      either by coagulation factor XIIIa or intracellular transglutaminase (protein
      glutamine:amine gamma-glutamyltransferase, EC 2.3.2.13). On the basis of inverse
      half-saturations of the enzymes, the order of acceptor substrate affinity for
      factor XIIIa was pEAQQIV much greater than Boc-AQQIV greater than Boc-QQIV, and
      for transglutaminase, Boc-QQIV greater than Boc-AQQIV greater than pEAQQIV (amino
      acid residues are shown in one-letter code; pE, pyroglutamic acid; Boc, tert
      butyloxycarbonyl). Sequence analysis of dansylcadaverine-substituted pEAQQIV
      indicated that the first of the two adjacent glutamine residues was the target of
      enzymatic modification. Boc-QIV showed no substrate activity with either enzyme.
      Crosslinking of crystallins in Ca2(+)-treated rabbit lens homogenate was readily
      inhibited by Boc-QQIV, Boc-AQQIV, and pEAQQIV, as was the formation of alpha
      chain polymers in human fibrin by pEAQQIV in the presence of human factor XIIIa.
      SDS/PAGE analysis suggested that the inhibitory peptides selectively blocked the
      electron donor functionalities in these enzymatic crosslinking reactions.

PMID- 1978325
TI  - Evidence for positive and negative regulation of the Hox-3.1 gene.
AB  - The region-specific patterns of expression of mouse homeobox genes are considered
      important for establishing the embryonic body plan. A 5-kilobase (kb) DNA
      fragment from the Hox-3.1 locus that is sufficient to confer region-specific
      expression to a beta-galactosidase reporter gene in transgenic mouse embryos has
      been defined. The observed reporter gene expression pattern closely parallels
      endogenous Hox-3.1 expression in 8- to 9.5-day postcoitum (p.c.) embryos. At 10.5
      days p.c. and later, the pattern of beta-galactosidase activity diverges from the
      Hox-3.1 pattern, and an inappropriately high level of reporter gene expression is
      observed in posterior spinal ganglia. Inclusion of an additional 2 kb of upstream
      sequences is sufficient to suppress this aberrant expression in the developing
      spinal ganglia. Together, these results show that the control of early Hox-3.1
      expression is complex, involving at least one positively acting and one
      negatively acting element.

PMID- 1978327
TI  - The metabolism of L-arginine and its significance for the biosynthesis of
      endothelium-derived relaxing factor: L-glutamine inhibits the generation of L
      arginine by cultured endothelial cells.
AB  - The mechanism by which L-glutamine (L-Gln) inhibits the release of endothelium
      derived relaxing factor from bovine aortic cultured endothelial cells was
      investigated. The intracellular concentration of L-arginine (L-Arg) in Arg
      depleted endothelial cells was inversely related to the level of L-Gln. Removal
      of L-Gln from the culture medium (usually containing L-Gln at 2 mM) abolished the
      inhibitory effect of the culture medium on L-Arg generation. L-Gln (0.2 and 2 mM)
      but not D-Gln inhibited the generation of L-Arg by both Arg-depleted and
      nondepleted endothelial cells. L-Gln did not interfere with the uptake of L-Arg
      or the metabolism of L-Arg-L-Phe to L-Arg but inhibited the formation of L-Arg
      from L-citrulline (L-Cit), L-Cit-L-Phe, and NG-monomethyl-L-arginine. L-Gln also
      inhibited the conversion of L-[14C]Cit to L-[14C]Arg by Arg-depleted endothelial
      cells. However, L-Gln did not inhibit the conversion of L-argininosuccinic acid
      to L-Arg by endothelial cell homogenates. Thus, L-Gln interferes with the
      conversion of L-Cit to L-Arg probably by acting on argininosuccinate synthetase
      rather than argininosuccinate lyase. L-Gln also inhibited the generation of L-Arg
      by the monocyte-macrophage cell line J774 but had no effect on the conversion of
      L-Cit to L-Arg by these cells. As the release of endothelium-derived relaxing
      factor from cultured and non-cultured endothelial cells is limited by the
      availability of L-Arg, endogenous L-Gln may play a regulatory role in the
      biosynthesis of endothelium-derived relaxing factor.

PMID- 1978328
TI  - Molecular mapping of the mouse db mutation.
AB  - Diabetes (db) is an autosomal recessive mutation located in the midportion of
      mouse chromosome 4 that results in profound obesity with hyperphagia, increased
      metabolic efficiency, and insulin resistance. To clone this gene and generate a
      molecular map of the region around this mutation, two genetic crosses were
      established: an intraspecific backcross between C57BL/6J db/db females and
      C57BL/6J db/db x DBA/2J +/+ F1 (B6D2 db/+ F1) male mice and an interspecific
      intercross between B6D2 db/+ F1 males and C57BL/6J db/db x Mus spretus F1
      (B6spretus db/+ F1) females. The progeny of both crosses were characterized for
      genotype at the db locus to map a series of restriction fragment length
      polymorphisms relative to the db locus. Measurements of body weight, body length,
      and plasma concentrations of glucose and insulin in the animals allowed the
      assignment of genotype (db/db vs. db/+ or +/+). A total of 132 progeny of the
      intraspecific cross and 48 db/db progeny of the interspecific cross were typed
      for individual restriction fragment length polymorphisms to generate a gene order
      of: centromere-brown (Mt4)-P lambda Mm3(2)-Ifa (Inta)-Cjun-db-D4Rp1-Glut1-Mtv-13
      Lck. Several of the genes that are linked to db [Cjun, glucose transporter
      (Glut1) and Lck] map to human chromosome 1p, suggesting that db may be part of a
      syntenic group between human 1p and the distal portion of mouse chromosome 4. In
      addition, phenotyping of the progeny of these crosses revealed a wide range in
      plasma concentrations of glucose and insulin among the obese progeny, with some
      animals developing overt diabetes and other remaining euglycemic. Distributions
      of age-controlled plasma [glucose] and [insulin] among the intraspecific-cross
      obese progeny were not bimodal, suggesting a role for polygenic differences
      between the progenitor strains (C57BL/6J and DBA/2J) in the development of overt
      diabetes.

PMID- 1978329
TI  - Correlation of the structure of the transmembrane domain of the neu oncogene
      encoded p185 protein with its function.
AB  - The human homologue of the neu oncogene is frequently found in human tumors.
      Certain amino acid substitutions at position 664 in the transmembrane domain of
      the neu oncogene-encoded p185 protein product are known to cause malignant
      transformation of cells. Using conformational energy analysis based on ECEPP
      (empirical conformational energies for polypeptides program), we have previously
      determined the preferred three-dimensional structures for the transmembrane
      domain of the p185 protein with a transforming (glutamic acid) and a
      nontransforming (valine) substitution at the critical position 664 and found that
      the global minimum-energy conformation of this region in the nontransforming
      protein contains a sharp bend, whereas the global minimum-energy conformation for
      this region from the transforming protein is entirely alpha-helical. We now
      demonstrate that this result holds for other known nontransforming (glycine,
      histidine, tyrosine, and lysine) and transforming (glutamine) substitutions at
      position 664. Furthermore, a simple statistical thermodynamic analysis of the
      results indicates that approximately 85% of each of the nontransforming sequences
      exist with the bend at positions 664 and 665, while approximately 90% of each of
      the transforming sequences exist as an alpha-helix. About 9% of the
      nontransforming sequences exist as the alpha-helix. These results suggest that if
      the intracellular concentration of the normal protein is increased at least 10
      fold, thereby increasing the alpha-helical form by this factor, cell
      transformation should result. This conclusion is directly supported by genetic
      experiments in which this level of overexpression of the normal protein was
      achieved with attendant cell transformation.

PMID- 1978330
TI  - Stem-cell organization in mouse small intestine.
AB  - We have investigated stem-cell organization in mouse small intestine (SI) by
      using a cellular marker induced by somatic mutation. In small intestinal whole
      mounts from heterozygous Dlb-1b/Dlb-1a mice stained with a peroxidase conjugate
      of Dolichos biflorus agglutinin (DBA-Px), mutations of Dlb-1b in stem cells
      result in loss of DBA-Px binding and so are recognizable as wholly or partly
      unstained crypts. The frequency of these clonal patterns can be measured during
      the accumulation of spontaneous mutations in untreated mice, or after treatment
      with ethylnitrosourea (ENU). The results show that there is a single infrequently
      dividing stem cell that maintains the epithelium of each crypt through a
      population of transit stem cells. The entire crypt epithelium is renewed
      approximately every 12 weeks.

PMID- 1978331
TI  - Evolutionary changes in the genetic code.
AB  - The genetic code has been influenced by directional mutation pressure affecting
      the base composition of DNA, sometimes in the direction of increased GC content
      and at other times, in the direction of AT. Such pressure led to changes in
      species-specific usages of codons and tRNA anticodons, and also in amino acid
      assignments of codons in mitochondria and in several intact organisms. These code
      changes are probably recent evolutionary events. The genetic code is not
      'frozen', but instead it is still evolving.

PMID- 1978332
TI  - Models of epidermal wound healing.
AB  - The spreading of cells across the surface of an epidermal wound enables epidermal
      migration to be studied independently of the wound contraction that occurs in
      deeper wounds. In particular, the stimulus for the increase in epidermal mitosis
      during would healing is uncertain. Our modelling suggests that biochemical
      regulation of mitosis is fundamental to the process, and that a single chemical
      with a simple regulatory effect can account for the healing of circular epidermal
      wounds. The model results compare well with experimental data.

PMID- 1978333
TI  - Resistance to human serum of gonococci in urethral exudates is reduced by
      neuraminidase.
AB  - Gonococci examined directly from urethral exudates are resistant to killing by
      human serum, but most strains become susceptible on subculture. Previous work
      with gonococci grown in vitro indicates that resistance in vivo is due to
      sialylation of gonococcal lipopolysaccharide (LPS) by a host factor, cytidine 5'
      monophospho-N-acetylneuraminic acid (CMP-NANA) or a related compound present in
      urogenital secretions and blood cells including phagocytes, which exude during
      inflammation. This sialylation inhibits the reaction between bactericidal IgM in
      serum and its target LPS sites. Here, we confirm the indication by using
      gonococci grown in vivo. Crucial to the above conclusions was the marked
      reduction of CMP-NANA-conferred serum resistance when gonococci were treated with
      neuraminidase to remove sialyl groups from their LPS. We now show that the serum
      resistance of gonococci in urethral exudates was reduced by treatment with
      neuraminidase from more than 95% (calculated in relation to controls incubated
      with heated serum) to 2-11% according to sample and incubation time. Subculture
      of the gonococci also reduced resistance to 9-11% but resistance was restored to
      more than 95% by incubation with CMP-NANA. This work is the culmination of an
      investigation that underlines the need to identify specific host factors and the
      virulence determinants they induce in vivo in future studies of pathogenicity.

PMID- 1978334
TI  - A case for ancestral transfer of symbionts between cockroaches and termites.
AB  - Living species of the cockroach family Cryptocercidae have intestinal symbionts
      that are congeneric with some of the gut protozoa found in Isoptera. Presence of
      such closely related symbionts in cryptocercids and in termites has been
      frequently interpreted as a uniquely derived homologous character shared between
      the two xylophagous groups. This may not be the most parsimonious interpretation.
      Cryptocercus nymphs placed into Zootermopsis (dampwood termite) colonies were
      killed and eaten by the termites. Termites placed into a Cryptocercus nest box
      were also fully consumed. Modern Cryptocercus punctulatus and Zootermopsis are
      often found in the same decaying logs in the Pacific Northwest of the U.S.A., and
      it is likely that their ancestors also cohabited in at least a portion of their
      ranges. By occasionally killing and consuming an intruder from the other group,
      gut protozoa could have been acquired and exchanged between termites and
      Cryptocercus or their ancestors, under natural conditions and before the life
      histories of the protozoa became specialized within the host orders. Implications
      for assessing the phylogeny of the two dictyopteroid groups are also discussed.

PMID- 1978335
TI  - Contrast and duration of exposure differentially affect vernier and stereoscopic
      acuity.
AB  - Although stereoacuity and vernier acuity both yield comparable thresholds well
      below the eye's resolution limit, the neural circuits for these two classes of
      visual responses do not process the signals in an identical manner. It had
      previously been demonstrated that hyperacuity is more resistant to image blur
      than stereoacuity and that the zones within which two targets must be placed to
      achieve the lowest thresholds differ quite radically. Two further differences are
      reported here: reduced contrast affects stereoacuity more severely than
      hyperacuity, as also does shortening of exposure into a range of tens of
      milliseconds, even when the Bunsen-Roscoe-Bloch law has been factored out.

PMID- 1978336
TI  - Modulation of expression of the hepatitis B virus surface antigen gene by the
      viral X-gene product.
AB  - Human hepatoma cells (HepG2 and HUH7) transfected with a plasmid (pHBV1004)
      containing the transcription units for the major surface antigen (S) mRNA and the
      X mRNA of hepatitis B virus (HBV) secreted surface antigen (HBsAg) into the
      culture medium. A frameshift mutation in the X gene carried by pHBV1004 greatly
      reduced HBsAg production by cells transfected with an equivalent amount of the
      mutant (pHBV1004-B). The mutation could be complemented by cotransfection with a
      plasmid (pSV2HBX) containing the X structural gene under control of the SV40
      early promoter. HBsAg production by cells cotransfected with pHBV1004-B and
      pSV2HBX was equivalent to that in cells transfected with the parent plasmid
      (pHBV1004) alone. Levels of HBsAg production were directly related to the amount
      of S mRNA produced, showing that the X-gene product (HBxAg) can modulate
      expression of the S gene.

PMID- 1978337
TI  - Excitatory synaptic currents in Purkinje cells.
AB  - The N-methyl-D-aspartate (NMDA) and non-NMDA classes of glutamate receptor
      combine in many regions of the central nervous system to form a dual-component
      excitatory postsynaptic current. Non-NMDA receptors mediate synaptic transmission
      at the resting potential, whereas NMDA receptors contribute during periods of
      postsynaptic depolarization and play a role in the generation of long-term
      synaptic potentiation. To investigate the receptor types underlying excitatory
      synaptic transmission in the cerebellum, we have recorded excitatory postsynaptic
      currents (EPSCS), by using whole-cell techniques, from Purkinje cells in adult
      rat cerebellar slices. Stimulation in the white matter or granule-cell layer
      resulted in an all-or-none synaptic current as a result of climbing-fibre
      activation. Stimulation in the molecular layer caused a graded synaptic current,
      as expected for activation of parallel fibres. When the parallel fibres were
      stimulated twice at an interval of 40 ms, the second EPSC was facilitated;
      similar paired-pulse stimulation of the climbing fibre resulted in a depression
      of the second EPSC. Both parallel-fibre and climbing-fibre responses exhibited
      linear current-voltage relations. At a holding potential of -40 mV or in the
      nominal absence of Mg2+ these synaptic responses were unaffected by the NMDA
      receptor antagonist 2-amino-5-phosphonovaleric acid (APV), but were blocked by
      the non-NMDA receptor antagonist 6-cyano-2,3-dihydro-7-nitroquinoxalinedione
      (CNQX). NMDA applied to the bath failed to evoke an inward current, whereas
      aspartate or glutamate induced a substantial current; this current was, however,
      largely reduced by CNQX, indicating that non-NMDA receptors mediate this
      response. These results indicate that both types of excitatory input to adult
      Purkinje cells are mediated exclusively by glutamate receptors of the non-NMDA
      type, and that these cells entirely lack NMDA receptors.

PMID- 1978338
TI  - The acquisition during development of Ca-activated potassium currents by cochlear
      hair cells of the chick.
AB  - Voltage-clamp recordings were done on hair cells from a region of the chick's
      cochlea. In the adult, these cells have voltage-sensitive Ca currents and rapid,
      Ca-activated K currents that together support an electrical resonance, showing
      voltage oscillations at frequencies greater than 100 Hz. In embryos 14-days old
      (at one week before hatching) the same cells had a voltage-sensitive Ca current
      like that in adults, but a more slowly acting K current (of the delayed-rectifier
      type). In current-clamp they could generate only slowly repetitive action
      potentials. By two days before hatching, Ca-activated K currents were present. We
      suggest that the acquisition of Ca-activated K currents contributes to functional
      maturation of the chick's cochlea.

PMID- 1978339
TI  - Vascular smooth muscle influences the release of endothelium-derived relaxing
      factor.
AB  - Conditioned medium was collected from vascular smooth-muscle cells grown in
      culture to determine if these cells synthesize vasoactive substances. The medium
      caused a short-acting endothelium-independent constriction of rat aorta, followed
      by a prolonged, endothelium-dependent relaxation. This relaxation was mediated
      through the release of endothelium-derived relaxing factor (EDRF) as it was
      abolished by the addition of methylene blue (5 x 10(-6) M), haemoglobin (10(-6)
      M) or methyl arginine, but was not affected by indomethacin (10(-5) M). Smooth
      muscle medium stimulated the production of EDRF from both rat and rabbit thoracic
      aortic rings as well as from cultured bovine pulmonary artery endothelial cells.
      The prolonged stimulation of EDRF by smooth-muscle medium was not mimicked by
      known physiological stimuli to EDRF release; EDRF-stimulating activity was not
      affected when smooth-muscle cells were grown in the presence of indomethacin (10(
      5) M), although serum in the medium was required. The EDRF-stimulating
      substance(s) in the smooth-muscle medium was heat stable and associated with a
      high molecular mass (30,000 greater than Mr greater than 3500) water-soluble
      species that is as yet unidentified.

PMID- 1978340
TI  - Tertiary structural constraints on protein evolutionary diversity: templates, key
      residues and structure prediction.
AB  - The pattern of residue substitution in divergently evolving families of globular
      proteins is highly variable. At each position in a fold there are constraints on
      the identities of amino acids from both the three-dimensional structure and the
      function of the protein. To characterize and quantify the structural constraints,
      we have made a comparative analysis of families of homologous globular proteins.
      Residues are classified according to amino acid type, secondary structure,
      accessibility of the sidechain, and existence of hydrogen bonds from sidechain to
      other sidechains or peptide carbonyl or amide functions. There are distinct
      patterns of substitution especially where residues are both solvent inaccessible
      and hydrogen bonded through their sidechains. The patterns of residue
      substitution can be used to construct templates or to identify 'key' residues if
      one or more structures are known. Conversely, analysis of conversation and
      substitution across a large family of aligned sequences in terms of substitution
      profiles can allow prediction of tertiary environment or indicate a functional
      role. Similar analyses can be used to test the validity of putative structures if
      several homologous sequences are available.

PMID- 1978341
TI  - Lack of response to family selection for directional asymmetry in Drosophila
      melanogaster: left and right are not distinguished in development.
AB  - Family selection for directional asymmetry in the expression of the Drosophila
      melanogaster mutant scute had no result. Fluctuating asymmetry did not show a
      selection differential correlated with directional asymmetry. The unfolding of
      bilateral symmetry in embryogenesis can be used to explain the lack of genetic
      variation for directional asymmetry. Directional asymmetry provides a well
      understood example of a developmental constraint in evolution. It is proposed
      that as no evidence is available for an independent left-right gradient in the
      embryo, quantitative traits can only be expressed variably along an existing
      gradient of positional information or a morphogen.

PMID- 1978342
TI  - GABA-induced potassium channels in cultured neurons.
AB  - When gamma-aminobutyric acid (GABA) or baclofen were applied to cultured rat
      hippocampal neurons, single-channel potassium currents appeared after a delay of
      30 s or more in patches of membrane on the cell surface isolated from the
      agonists by the recording pipette. The appearance of currents in patches not
      exposed to agonist, the delay in their appearance and the suppression of currents
      in cells pre-incubated with pertussis toxin indicate the involvement of an
      intracellular second messenger system. The channels were associated with a GABAB
      receptor rather than a GABAA receptor as they were blocked by baclofen, a GABAB
      antagonist, but were not affected by bicuculline, a GABAA antagonist. A feature
      of the single channel currents was their variable amplitude: they had a maximum
      conductance of ca. 70 pS and displayed many lower conductance states that were
      integral multiples of 5-6 pS. In several cells exposed to GABA or baclofen, first
      small currents and then progressively larger currents appeared: current amplitude
      was a multiple of an elementary current. It is suggested that binding of GABA to
      GABAB receptors activates a second messenger system causing opening of oligomeric
      potassium channels.

PMID- 1978343
TI  - Changes in goldfish retinal ganglion cells during axonal regeneration.
AB  - Recent work suggests that mammalian retinal ganglion cells may become more like
      developing ganglion cells in form while regenerating through a peripheral nerve
      graft. We have injected Lucifer Yellow into regenerating ganglion cells of
      goldfish to look for similar changes. Within three weeks of injury, we saw dye
      coupling to nearby cells, which is a common developmental feature in many
      species. Dendrites and axons, which in most mature ganglion cells are smooth,
      became varicose and hairy, like those examined in mammalian development.
      Secondary axons arose later, not only as side-branches of the primary axon but
      also from the soma, as in mammalian development and regeneration. Since, in fish,
      these responses are clearly an intrinsic part of functional regeneration, their
      equivalence in fish and mammals strengthens the view that a similar regenerative
      competence may exist in the retinal ganglion cells of all vertebrates.

PMID- 1978345
TI  - Genetic sequences.

PMID- 1978344
TI  - Changes in the conductance of the neuronal nicotinic acetylcholine receptor
      channel induced by magnesium.
AB  - We have investigated the effect of magnesium on the single-channel conductance of
      neuronal nicotinic acetylcholine receptors (nAChRs) in nerve growth-factor
      treated rat pheochromocytoma (PC12) cells. The patch-clamp technique was used to
      record single-channel currents from cell attached and excised, outside-out
      patches in the presence of various internal and external Mg2+ concentrations.
      Mg2+ reduced the single-channel conductance in a concentration-dependent manner
      with an IC50 of 9.2 mM for external Mg2+ (inward conductance) and 0.69 mM for
      external Mg2+ (outward conductance). Both estimated and measured conductances for
      divalent cation-free CsCl solutions were around 60 pS. We also find that divalent
      cations are not involved in the inward rectification of whole-cell ACh-induced
      currents in these cells. Our results imply that the amino acids screened by
      divalent cations sense electric fields only weakly and are presumably outside the
      lipid bilayer. They also suggest that the density and the number of charges (or
      both) differ on either side of the ion pore.

PMID- 1978346
TI  - Neuronal discharge hypersynchrony and the intracranial water balance in relation
      to glutamic acid and taurine redistribution: migraine and epilepsy.

PMID- 1978347
TI  - Taurine: functional neurochemistry, physiology, and cardiology. Proceedings of a
      symposium. Moguer, Spain, April 19-22, 1989.

PMID- 1978348
TI  - Possible role of glutamate with taurine in neuron-glia interaction during
      cerebellar development.

PMID- 1978349
TI  - Taurine as a neuromodulator in the insect central nervous system.

PMID- 1978350
TI  - Stimulated taurine release from different brain preparations: changes during
      development and aging.

PMID- 1978351
TI  - Neuromodulatory and trophic actions of taurine.

PMID- 1978352
TI  - Effects of therapy on biology and kinetics of the residual tumor, Part B:
      clinical aspects. Proceedings of an international symposium. Vancouver, British
      Columbia, Canada, February 15-18, 1989.

PMID- 1978353
TI  - Chlorpromazine and clothiapine actions at the level of the CNS and vas deferens.
AB  - CNS-level changes caused by chlorpromazine and clothiapine, a structural
      analogue, were studied with a battery of behavioral tests in rats, along with the
      ability of these two drugs to antagonize electrically and alpha-stimulator
      (phenylephrine-)induced contractions in the rat vas deferens. The findings
      indicated that clothiapine, while less effective as an alpha-receptor antagonist,
      was a much more active CNS-depressant than chlorpromazine.

PMID- 1978354
TI  - Pyrimidobenzodiazepines. Synthesis of pirenzepine analog.
AB  - The synthesis of Pyrimido[4,5-b][1,5]benzodiazepine derivatives from 4-(o
      aminophenylene)amino-5-ethoxy-carbonyl-1,2-dihydro-6-methyl-2 - oxopyrimidine has
      been described. Pyrimidobenzodiazepine 5 alkylated with N-methyl-N'-chloroacetyl
      piperazine gives a product related to pirenzepine. Compound 5 shows weak
      antianxiety and antidepressive action.

PMID- 1978355
TI  - Inhibition of stress-induced gastric ulcers by sulphasalazine and its
      constituents (sulphapyridine and 5-aminosalicylic acid) in rats.
AB  - The effects of sulphasalazine and of its major constituents, sulphapyridine and 5
      aminosalicylic acid (5-ASA), on gastric ulceration as well as on changes in mast
      cell counts and mucus levels in the glandular mucosa were examined in restrained
      rats exposed to 4 degrees C (stress) for 2 h. Sulphasalazine (50, 100, 200
      mg/kg), sulphapyridine (31.25, 62.5, 125 mg/kg) or 5-ASA (18.75, 37.5, 75 mg/kg)
      was injected subcutaneously 0.5 h before stress induction. Cold-restraint stress
      produced gastric glandular mucosal ulcers which were significantly reduced by all
      three doses of sulphasalazine and the higher doses of sulphapyridine and 5-ASA.
      Sulphasalazine prevented mast cell degranulation and increased the amount of
      mucus adhering to the mucosa. In contrast, the higher doses of sulphapyridine
      significantly increased only the mucus levels, whereas those of 5-ASA effectively
      prevented mast cell degranulation. The results show that the total effect of
      sulphasalazine is approximately equivalent to the summation of the actions of its
      component doses of sulphapyridine and 5-ASA. It is notable that sulphapyridine
      itself appears to be biologically active in reducing ulcer severity.

PMID- 1978356
TI  - Beta-adrenergic receptors on human lymphocytes: comparison of down-regulation in
      vivo and in vitro.
AB  - beta-Adrenergic receptors on isolated human lymphocytes were enumerated using
      125I-cyanopindolol (125I-CYP), after a 90-min exposure to 50 mumols/l l
      isoproterenol in vitro. No change in receptor density could be shown in assays
      performed at 37 degrees C, although a 40% reduction was apparent in binding
      studies carried out at 4 degrees C. In contrast, beta-adrenergic receptors on
      lymphocytes from mild asthmatics after a 3-week course of oral terbutaline showed
      a 40% reduction in receptor density regardless of the assay temperature, in
      addition to a 2.5-fold reduction in the receptor affinity for isoproterenol. The
      data are consistent with reports that a fraction of receptors are sequestered
      during short-term exposure to agonists. Sequestered receptors may or may not be
      detected by radioligand binding assays depending on the ligand of choice,
      temperature of the binding assay and duration of prior exposure to the agonist.
      After extended exposure to an agonist in vivo, the number of surface receptors
      was reduced, and sequestered receptors were not present, presumably as a result
      of degradation.

PMID- 1978357
TI  - Song learning: the interface between behaviour and neuroethology.
AB  - The high degree of developmental plasticity displayed by the songs of oscine
      birds makes them appropriate subjects for research on the etiology and
      neurobiology of vocal learning. Strong individual differences and learned local
      dialects are common. The readiness to acquire new songs appears to persist
      throughout life in some species and is restricted to relatively short sensitive
      periods in others. Learning can occur with remarkably few exposures to song.
      Mimicry of other species occurs but, given a choice, there is a tendency to
      favour conspecific songs. Evidence is presented for two kinds of vocal learning,
      one 'memory-based', the other 'action-based.' Subsong and 'plastic song' phases
      of motor development appear to be obligatory steps in the ontogeny of learned
      songs. A case is made that acquisition and production should be viewed as
      distinct phenomena with different physiological correlates. Research on
      behavioural development is closely associated with studies of the physiology of
      development. The two are mutually synergistic, and the synergism is well
      displayed in research on song learning in birds. This review of some of the
      characteristics of avian vocal learning as derived from behavioural studies,
      indicates lacunae in our knowledge about the ethology of song learning, and
      suggests how the comparative study of vocal development can pave the way for new
      insights into the underlying neurobiology.

PMID- 1978358
TI  - Song learning in birds: the relation between perception and production.
AB  - The vocal control system of oscine songbirds has some perplexing properties--e.g.
      laterality, adult neurogenesis, neuronal replacement--that are not predicted by
      common views of how vocal learning takes place. Similarly, we do not understand
      the relation between the direct pathway for the control of learned song and the
      recursive pathway necessary for song learning. Some of the paradoxes of the vocal
      system of birds may disappear once the relation between the perception and
      production of learned vocalizations is better understood. To some extent,
      perception and production may be two closely related states of a same system.

PMID- 1978359
TI  - Neural bases of recognition memory investigated through an analysis of
      imprinting.
AB  - Through a learning process known as imprinting, the young of some animals,
      including the domestic chick, come to recognize an object by being exposed to it.
      Visually naive chicks vigorously approach a wide range of objects. After an
      adequate period of exposure to one object chicks selectively approach it in a
      recognition test. The nervous system of dark-reared chicks is not a tabula rasa,
      as chicks have predispositions to approach some stimuli rather than others.
      Nevertheless, visual imprinting leads to changes in a nervous system that may not
      have been 'marked' by previous visual experience, and so encourages the hope of
      discovering the neural bases of the learning process. The intermediate and medial
      part of the hyperstriatum ventrale, a sheet of cells within the cerebral
      hemispheres, plays a crucial role in visual imprinting, particularly in the
      memory process of recognition. The cellular and sub-cellular changes that take
      place in this part of the hyperstriatum ventrale after imprinting are described.
      The right and left hyperstriatum ventrale regions play different roles in the
      imprinting process, and evidence is given for the existence of multiple memory
      systems in the chick brain.

PMID- 1978360
TI  - Food-storing birds: adaptive specialization in brain and behaviour?
AB  - Among the passerine birds, species that store food have an enlarged hippocampal
      region (dorso-medial cortex), relative to brain and body size, when compared with
      the non-storers. The volume of one of the major afferent-efferent pathways (the
      septo-hippocampal pathway) is also greater in food storing species. This
      specialization of brain structure is discussed in relation to behavioural studies
      in which the spatial memory of storing and non-storing species has been compared.

PMID- 1978361
TI  - Neural mechanisms of classical conditioning in mammals.
AB  - Evidence supports the view that 'memory traces' are formed in the hippocampus and
      in the cerebellum in classical conditioning of discrete behavioural responses. In
      the hippocampus learning results in long-lasting increases in excitability of
      pyramidal neurons that resemble the phenomenon of long-term potentiation.
      Although it plays a role in certain aspects of conditioning, the hippocampus is
      not necessary for learning and memory of the basic conditioned responses. The
      cerebellum and its associated brain-stem circuitry, on the other hand, does
      appear to be essential (necessary and sufficient) for learning and memory of the
      conditioned response. Evidence to date supports the view that mossy fibre convey
      conditioned stimulus information and that climbing fibres conveys the critical
      'reinforcement' information to the cerebellum and that 'memory traces' appear to
      be formed in cerebellar cortex and interpositus nucleus.

PMID- 1978363
TI  - The conditioning connection.
AB  - In 1948 Konorski argued that conditioning reflects the strengthening of a
      connection between elements representing the signal and the reinforcer, as a
      result of the coincidence of activity in the signal element with a rise in
      activity in the reinforcer element. This Konorskian process represents one way of
      implementing an error-correcting learning rule and thus, unlike a simple Hebbian
      process, anticipates selective conditioning, such as that observed in Kamin's
      blocking procedure. However, the Konorskian process, in common with other error
      correcting learning rules, fails to explain why blocking is attenuated by
      'surprising' changes in reinforcement conditions that should not augment activity
      in the reinforcer element. Rather, the reinforcer-specificity of such unblocking
      suggests the operation of an associability process by which stored information
      about the past predictive history of the signal is expressed at the connection
      between signal and reinforcer elements to modulate changes in the connection
      weight.

PMID- 1978362
TI  - Multiple forms of non-associative plasticity in Aplysia: a behavioural, cellular
      and pharmacological analysis.
AB  - A complete understanding of the cellular mechanisms underlying the formation of
      associations between stimuli, as occurs during classical conditioning, requires
      an understanding of the non-associative effects of the individual stimuli. The
      siphon withdrawal reflex of Aplysia exhibits both non-associative and associative
      learning when a tactile stimulus to the siphon serves as a conditioned stimulus,
      and tail shock serves as an unconditioned stimulus. In this chapter we describe
      experiments which examine the non-associative effects of tail shock at three
      different levels of analysis. At a behavioural level we found that the magnitude,
      and even the sign of reflex modulation induced by tail shock depended critically
      on three parameters: (i) the state of the reflex (habituated or non-habituated);
      (ii) the strength of the tail shock, and (iii) the time of testing after tail
      shock. Specifically, when non-habituated responses produced by water jet stimuli
      to the siphon were examined, tail shock produced transient inhibition 90 s later;
      facilitation of non-habituated responses (sensitization) only emerged after a
      considerable delay of 20-30 min. When habituated responses were examined, tail
      shock produced immediate facilitation (dishabituation); the amount of
      facilitation was inversely related to the strength of tail shock, with stronger
      shock producing no dishabituation. At a cellular level it was found that the
      complex excitatory postsynaptic potential (EPSP) in siphon motor neurons produced
      by water jet stimuli to the siphon provides a reliable cellular correlate of
      several of the non-associative effects of tail shock that we observe
      behaviourally. When non-decremented complex EPSPS were examined, strong tail
      shock produced transient inhibition at a test 90 s after shock.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1978364
TI  - Hippocampal synaptic plasticity and NMDA receptors: a role in information
      storage?
AB  - There has recently been renewed interest in the idea that alterations in synaptic
      efficacy may be the neural basis of information storage. Particular attention has
      been focused upon long-term potentiation (LTP), a long-lasting, but
      experimentally induced synaptic change whose physiological properties point to it
      being a candidate memory mechanism. However, considerations of storage capacity
      and the possibility of concomitant activity-dependent synaptic depression make it
      unlikely that individual learning experiences will give rise to gross changes in
      field potentials similar to those that occur in LTP, even if learning and LTP
      utilize common neural mechanisms. One way of investigating the functional
      significance of LTP is to use selective antagonists of those excitatory amino
      acid receptors whose activation is essential for its induction. This paper
      discusses various design requirements for such experiments and reviews work
      indicating that the N-methyl-D-aspartate receptor antagonist AP5 causes a
      behaviourally selective learning impairment having certain common features to the
      behavioural profile seen after hippocampal lesions. Two new studies are described
      whose results show that AP5 has no effect upon the retrieval of previously
      established memories, and that the dose-response profile of the impairment of
      spatial learning occurs across a range of extracellular concentrations in
      hippocampus for which receptor selectivity exists. These experiments show that
      activation of NMDA receptors is essential for certain kinds of learning.

PMID- 1978365
TI  - An assessment of Marr's theory of the hippocampus as a temporary memory store.
AB  - The recent reawakened interest in 'neural' networks begs the question of their
      relevance to the analysis of real nervous systems. Network models have been
      criticized for the lack of realism of their individual components, and because
      the architectures required by some neural-network algorithms do not seem to exist
      in real nervous systems. In three related papers published in the 1970s, David
      Marr proposed that the cerebellum, the neocortex and the hippocampus each acts as
      a memorizing device. These theories were intended to satisfy the biological
      constraints, but in computational terms they are undetermined. In this paper we
      reassess Marr's theory of the hippocampus as a temporary memory store. We give a
      complete computational account of the theory and we show that Marr's
      computational arguments do not sufficiently constrain his choice of model. We
      discuss Marr's specific model of temporary memory with reference to the
      neurophysiology and neuroanatomy of the mammalian hippocampus. Our analysis is
      supported by simulation studies done on various memory models built according to
      the principles advocated by Marr.

PMID- 1978366
TI  - The Croonian lecture, 1990. The interdependence of the behavioural sciences.

PMID- 1978367
TI  - Problems of learning and memory: one or multiple memory systems?
AB  - Learning, and hence memory, is ubiquitous not only throughout the animal kingdom,
      but apparently throughout many regions of the brain. Is all learning reducible to
      a single common form? Neuropsychological dissociations suggest that the mammalian
      brain possesses a number of different and potentially independent memory systems,
      with different mechanisms and anatomical dispositions, some of which are neurally
      widely dispersed and others of which are narrowly organized. Among the types
      considered are: (i) short-term memory; (ii) knowledge and skills; (iii) stable
      associative memory; (iv) event memory; and (v) priming. As double or multiple
      dissociations do not lead to logically inevitable conclusions, it has been argued
      that an alternative to multiple memory systems is variable modes of processing.
      But these, too, would be dissociable on the same lines of evidence.
      Dissociations, if strong and absolute, have strong pragmatic power when they are
      combined with evolutionary and neuroscientific evidence. Multiple memory systems
      may possibly share some common cellular mechanisms, but such mechanisms do not
      define the separate properties at the systems level.

PMID- 1978368
TI  - Small toe muscles for defect coverage.
AB  - Defects on the sole of the foot are always a major problem. Frequently, these
      patients suffer from other diseases, such as diabetes mellitus, chronic vascular
      diseases, or skeletal deformities. Usually, these are full-thickness defects and
      the bone is exposed. Beside other possibilities, the short muscles of the fifth
      toe provide a viable muscle flap for coverage of small defects, especially on the
      lateral side of the foot.

PMID- 1978369
TI  - Cerebrospinal fluid somatostatin in delirium. II. Changes at the acute stage and
      at one year follow-up.
AB  - Cerebrospinal fluid somatostatin-like immunoreactivity (CSF SLI) was determined
      for elderly delirious patients during the acute stage and after one-year follow
      up. The SLI levels were compared with age-equivalent controls. For the group as a
      whole, and also when the group was subdivided according to the severity of
      cognitive decline at the acute stage, type of delirium, or the central nervous
      system disease, delirious patients showed significant reduction of SLI as
      compared with the controls. In the follow-up, we observed a further reduction of
      CSF SLI together with significant correlations in the second and third samples
      between SLI levels and Mini-Mental State Examination score. Our results suggest a
      role for somatostatinergic dysfunction in the genesis of some symptoms of
      delirium. This dysfunction may be a common phenomenon in various forms of
      delirium and dementia.

PMID- 1978370
TI  - Gepirone as a 5-HT1A agonist in the treatment of major depression.
AB  - Twenty-four patients with major depression were treated in a single-blind design
      with 25 mg to 75 mg gepirone, a pyrimidinyl piperidinedione analog of buspirone
      with serotonin1A (5-HT1A) receptor affinity properties. Twenty-four-Item Hamilton
      Rating Scale for Depression-(HAM-D) scores decreased by 36 percent when mean
      baseline scores were compared with an endpoint analysis of 6 weeks' gepirone
      treatment. Several subjects demonstrated marked improvements over baseline. The
      data are discussed within the context of 5-HT1A receptor desensitization as a
      potential component of antidepressant treatment.

PMID- 1978371
TI  - Efficacy and safety of a putative anxiolytic agent: ipsapirone.
AB  - Ipsapirone is an azopirone derivative that selectively interacts with serotonin
      1A (5-HT1A) receptors and fails to affect other neurotransmitter receptors. In
      this study, ipsapirone at 15 mg or 30 mg was compared with diazepam at 15 mg and
      placebo in a double-blind, random assignment study design in patients with
      generalized anxiety disorder (GAD). During 4 weeks of treatment, both active
      drugs were therapeutically superior to placebo, without significant drug vs. drug
      therapeutic differences. The side-effect profile of ipsapirone at 15 mg was
      favorable compared to diazepam, but at 30 mg ipsapirone produced significant
      gastrointestinal disturbances.

PMID- 1978372
TI  - Ipsapirone: evidence for efficacy in depression.
AB  - Sixty-five inpatients of a psychosomatic hospital in the Federal Republic of
      Germany with the diagnosis of anxiety neurosis (n = 31) or neurotic depression (n
      = 34) as defined by the International Classification of Disease (ICD-9), were
      randomized to a 4-week course of ipsapirone at 7.5 mg t.i.d. or placebo in a
      prospective, double-blind clinical trial to assess safety, tolerability, and
      efficacy. This article reports the efficacy results for those patients with the
      diagnosis of neurotic depression. The primary efficacy variable for patients with
      neurotic depression was the change from baseline in the Hamilton Rating Scale for
      Depression (HAM-D) at 4 weeks of treatment. Considering all of the randomized
      patients with neurotic depression (n = 34, the intent-to-treat population), the
      mean change from baseline in the HAM-D at Week 4 (observed cases) was -13.13 +/-
      6.06 (n = 16) for the ipsapirone group, and -3.19 +/- 5.99 (n = 16) for the
      placebo group (p less than .001). A parallel analysis of the change from baseline
      in the Core Depression score of the HAM-D (defined as the sum of items 1, 2, 3,
      7, and 8) also showed a significant treatment difference (p less than .01).
      Results were similar for the intent-to-treat population, last observation carried
      forward. Safety and tolerability were evaluated for all study patients
      independent of diagnosis. Treatment-emergent events (n = 65) were reported by 76
      percent of patients treated with ipsapirone (n = 33) and by 38 percent of
      patients treated with placebo (n = 32).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1978373
TI  - Is maintenance antiparkinsonian treatment necessary?
AB  - The authors designed a three-phase prospective trial in which only those patients
      who developed an acute, neuroleptic-induced extrapyramidal side effect (EPSE)
      received benztropine (BZ) at 2 mg i.m. and then 1 mg p.o. b.i.d. for 2 days after
      their symptoms were rated for severity and type (Preparatory Phase 1). They were
      then randomly assigned under double-blind conditions to continue BZ or be
      switched to placebo for 8 days (Experimental Phase 2). Finally in Phase 3
      (Followup), all patients continued on placebo in a single-blind design until Day
      30. If the patient re-experienced an acute EPSE that was of sufficient severity
      to require immediate BZ administration, he or she was rated, treated, and then
      dropped from the study. EPSE scores and dropout rates did not differ in Phase 2
      between the placebo- and BZ-treated groups. Implications for the continuation,
      cessation, or intermittent use of antiparkinsonian (AP) drugs are discussed.

PMID- 1978374
TI  - Ionizing radiation damage to DNA: molecular aspects.

PMID- 1978375
TI  - Preclinical and clinical studies with somatostatin related to the central nervous
      system.
AB  - 1. The tetradecapeptide somatostatin (SS) has a widespread, uneven distribution
      within several organs including the central nervous system (CNS), with
      particularly high concentration in the hypothalamus. 2. The SS-related peptides
      (SS28, SS28(1-12), SS28(15-28)) are originated from the precursor pre
      prosomatostatin. 3. SS is suggested to be involved in a large number of CNS
      functions, locomotion, sedation, excitation, catatonia, body temperature,
      feeding, nociception, paradoxical sleep, self-stimulation, seizure, learning and
      memory. 4. SS influences central neurochemical processes. 5. It is possible that
      SS is related to various neurological and psychiatric illnesses, like
      Huntington's disease, multiple sclerosis, Parkinson's disease, epilepsy, eating
      disorders, Alzheimer's disease, schizophrenia and major depressive illness.

PMID- 1978376
TI  - [Molecular analysis of muscle differentiation].

PMID- 1978377
TI  - [The bioconductive connectional system: radiobiologic and therapeutic
      implications].

PMID- 1978378
TI  - Conference on newer aspects in the treatment of renal failure. September 8-10,
      1989, Geneva, Switzerland. Abstracts.

PMID- 1978379
TI  - [Application of electro-erosion in 2-stage denture construction].

PMID- 1978380
TI  - Morphology and functional activity of gastroenteropancreatic neuroendocrine
      tumours.

PMID- 1978381
TI  - Clinical implications of the diffuse gastroenteropancreatic endocrine system.

PMID- 1978382
TI  - Endocrine aspects of medullary thyroid carcinoma.

PMID- 1978383
TI  - Multiple endocrine neoplasia type II.

PMID- 1978384
TI  - Occupational cancer epidemiology. A symposium. Vancouver, June 1988. Proceedings.

PMID- 1978385
TI  - Effect of stobadine and histamine H1 and H2 blockers on histamine-induced
      contraction of guinea pig airways in vitro.
AB  - Histamine, a nonselective histamine receptor agonist, activates simultaneously
      both H1 and H2 receptors in the guinea pig trachea and lung strip. The resulting
      contraction is due to the prevalence of H1 receptors, because they are blocked by
      the selective H1 antagonist diphenhydramine. The H2 receptor antagonists
      cimetidine and ranitidine increased the sensitivity of both tissues to histamine
      by affecting primarily the amplitude of contractions induced by high histamine
      concentrations. Since the lung strips were more sensitized by ranitidine and low
      concentrations of the other studied antagonists (diphenhydramine, dithiadene,
      stobadine) than the tracheal smooth muscle, it is inferred that the density of H2
      receptors is higher in peripheral than central airways. From all the studied
      histamine receptor antagonists only dithiadene was able to unmask the relaxation
      induced by H2 receptor activation indicative of its highest H1 selectivity. In
      the light of the concentration-dependent antihistaminic effect of stobadine, i.e.
      potentiation in low and inhibition in high concentrations, stobadine is suggested
      to belong to antihistaminics with no histamine receptor subtype selectivity.

PMID- 1978387
TI  - The IXth UOEH International Symposium and the First Pan Pacific Cooperative
      Symposium. Industrialization and emerging environmental health issues--risk
      assessment and risk management. 2-6 October, 1989, Kitakyushu, Japan.

PMID- 1978386
TI  - [A study on tolerance to denopamine, oral beta 1-agonist].
AB  - To investigate whether effects of denopamine become weaker or not. Initial single
      dose (10 mg) effects, single dose effects after long-term treatment (30 mg per
      day, about 40 days), and chronic effects were studied by Doppler and
      echocardiography in 23 patients with heart failure (NYHA II-III). 1) Chronic
      effects: Blood pressure and heart rates didn't change significantly whether they
      were measured before or after long-term treatment. But left ventricular end
      diastolic dimension decreased from 54.6 +/- 10.2 to 53.3 +/- 10.1 mm (p less than
      0.01). Percent fractional shortening (%FS) increased from 22.6 +/- 7.8 to 25.3 +/
      8.6% (p less than 0.05). Mean velocity of circumferential fiber shortening
      (mVCF) tended to increase, and cardiac index (CI) increased from 2.71 +/- 0.47 to
      2.98 +/- 0.57 l/min/m2 (p less than 0.01). 2) Initial single dose effects: Blood
      pressure and heart rates increased significantly. %FS increased from 25.0 +/- 7.7
      to 25.9 +/- 7.8% (p less than 0.05), mVCF increased from 0.94 +/- 0.26 to 1.03 +/
      0.28 cir/sec (p less than 0.01), and CI increased from 2.81 +/- 0.49 to 3.09 +/-
      0.49 l/min/m2 (p less than 0.01). 3) Single dose effects after long-term
      treatment: Blood pressure and heart rates increased significantly. %FS tended to
      increase, mVCF increased from 1.02 +/- 0.27 to 1.09 +/- 0.30 cir/sec (p less than
      0.05), and CI increased from 3.05 +/- 0.62 to 3.37 +/- 0.54 l/min/m2 (p less than
      0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1978388
TI  - [The current diagnostic and treatment aspects of nonrheumatic mitral
      valvulopathies].

PMID- 1978389
TI  - [Ischemic mitral insufficiency: its mechanisms and the therapeutic implications].

PMID- 1978390
TI  - [The etiological spectrum of pure and isolated chronic mitral insufficiency].
AB  - The 78 patients with mitral insufficiency studied in the present paper were
      chosen taking into consideration the following: regurgitant apex holosystolic or
      mesotelesystolic murmur, noise 3 and the dilation of the left atrium and/or left
      ventricle at Echo-20. The patients were investigated clinically, ECG,
      phonocardiographically and echographically (2D). The etiology was established in
      75 patients; non rheumatic causes were present in 70% of the cases. The
      echographic study, besides the other methods, is very important in diagnosing the
      mitral insufficiency, in etiology, severity and the degree of deterioration of
      the pump function of the left ventricle. The Eco-2D examination, a noninvasive
      method, allows reaching therapeutic medical and surgical decisions at the best
      moment and helps in assessing the results.

PMID- 1978391
TI  - [The etiological spectrum of mitral insufficiency: a 10-year retrospective
      study].
AB  - The incidence, etiology and data on the severity and therapeutic implications of
      the mitral insufficiency were investigated in the patients admitted in the clinic
      during 10 years. The diagnosis was based mainly on clinical and echocardiography
      mode M data. 595 patients suffering from mitral insufficiency (below 2% of the
      total of the patients admitted) were recorded. In 65% of the cases mitral
      insufficiency had a rheumatic etiology (the majority associated
      polyvalvulopathies), in 14.8% an ischaemic origin, and in 10.9% an organic
      functional one (the left ventricle was dilated). The primary prolapse of the
      mitral valve appeared in 6.9% of the cases (the low incidence was explained by
      the severe criteria applied in positive diagnosis). 4 cases of rupture of the
      subvalvular apparatus are described in the patients suffering from prolapse. All
      of them had a sudden onset, by severe cardiac insufficiency without a clear
      cause, appeared under conditions of seemingly complete health. Intense therapy
      followed by valvular prosthesis, resulted in a spectacular recovery of the heart
      function.

PMID- 1978392
TI  - [Infectious endocarditis in mitral valve prolapse].
AB  - The paper reports on 13 cases of infectious endocarditis in the patients with
      prolapse of the mitral valve admitted for a period of 10 years (1979-1989) into
      the Clinic of Cardiology of the Fundeni Hospital. These cases stand for 3.6% of
      the cases with prolapse of the mitral valve admitted during that period, and 5%
      of the patients with infectious endocarditis. Our study dealt only with the cases
      of the prolapse of the mitral valve, clinically and echographically documented
      before the appearance of the septic graft. The hemocultures were positive in all
      the patients (viridans streptococci in 84.61% cases). The symptomatology, the
      clinical objective data and the paraclinical results (phonocardiographic,
      echocardiographic, electrocardiographic, radiologic, investigations with
      isotopes), the response to the treatment (medical, surgical) and the evolution in
      time were analyzed. An increase was found during endocarditis in the number of
      patients with holosystolic murmurs (30.7% cases) versus those with click
      telesystolic murmur, the appearance in 41.15% of the cases of valvular
      vegetations at the Echo examination, and in 15.38% cases of ruptures of cordages.
      Mitral insufficiency secondary to endocarditis became worse, in 30.76% cases. The
      treatment with antibiotics resulted in the healing of the infection in all the
      cases. The surgery was not necessary in any patient during the evolution of
      endocarditis. The surgery (valvular prosthesis) was made in 23.07% cases, which
      presented, after curing the septic graft, important mitral regurgitation with
      cardiac insufficiency refractory to the medical treatment. Prophylaxis of the
      infectious endocarditis in the prolapse of mitral valve with mitral regurgitation
      is necessary.

PMID- 1978393
TI  - [Arrhythmias in patients with mitral valve prolapse].
AB  - The object of the present investigation was the discovery of the arrhythmias in
      the patients with prolapse of the mitral valve (PMV), the types of arrhythmias,
      the factors favouring them, the therapy used. In a group of 126 patients
      suffering from PMV, 25 had mitral insufficiency, and 48% of the cases had
      arrhythmias too. The ventricular arrhythmias existed in 18 patients, in the most
      of them as ventricular extrasystoles. Only in 2 cases, ventricular paroxysmal
      tachycardia was noticed, and only one case of ventricular fibrillation was
      recorded. The following conclusions were drawn from the study: the increase of
      arrhythmias is low, their appearance is correlated with mitral insufficiency,
      ventricular arrhythmias are predominant, the majority are benign, they are more
      frequent than in the patients with neurovegetative dystonia (if considering the
      prolapse associated with systolic murmur), necessity of periodic control for
      discovering the cases with high risk of ventricular arrhythmias with malignant
      potential.

PMID- 1978394
TI  - [Mitral valve prolapse. An echocardiographic study of 456 cases].
AB  - The prolapse of the mitral valve is an affection arousing much interest from the
      clinical and echocardiographical viewpoints. The present paper reports on the
      analysis of 456 cases (322 women--70% and 134 men--29.39%), suffering from
      prolapse of the mitral valve, selected out of 15,714 echocardiographic
      examinations (2.93%). All the patients were examined echocardiographically--Echo)
      in the M mode and bidimensionally; 256 cases underwent an Echo-Doppler
      examination, too and in 90 cases the phonocardiogram was also used. 983 cases
      were diagnosed as clinically suffering from prolapse, confirmed by Echo in 291
      cases (29.62%), and in 165 cases the diagnosis was established only clinically.
      Phonocardiographically, the most frequent were recorded the mesotelesystolic
      click (40%), followed by click + holosystolic murmur (31.11%), telesystolic
      murmur (19.70%), holosystolic murmur (6.66%). The prolapse of the mitral valve
      was evidenced in 394 cases, both by M-Echo and by 2D-Echo; in 28 (6.1%) cases it
      was evidenced only by M-Echo, and in 34 cases (7.4%) only by 2D-Echo. In 62 cases
      (13.4%) the prolapse was better evidenced when the patients stood. The most
      affected was the anterior mitral valve, 203 cases (44.5%). The conclusion was
      drawn that the prevalence of the prolapse of the mitral valve is of 2.93%
      according to the Echo examination. A correct diagnosis requires the use of a
      rigorous examination technique and the observance of the clinical and Echo
      diagnosis criteria.

PMID- 1978395
TI  - [Doppler echocardiography in mitral insufficiency].
AB  - The Doppler method (pulsatile and continuous) was used for finding out and
      semiquantitatively evaluating the mitral insufficiency of various etiologies:
      inflammatory (rheumatic); prolapse of mitral valve; obstructive hypertrophic
      cardiomyopathy; dilatative cardiomyopathy; calcification of valvular ring. The
      Doppler parameters obtained after automatic processing of the image (speed
      transvalvular pressure gradient, flow period and acceleration) offer data on the
      diastolic performance of the left ventricle. Registration of the aortic flow
      makes possible the calculation of the cardiac flow (the diameter of the aorta is
      measured in echo-B), and of the aortic flow permits the noninvasive evaluation of
      the lung arterial pressure. The method offers a large vista in the noninvasive
      evaluation of the patients suffering from mitral insufficiency.

PMID- 1978396
TI  - [The surgical treatment of nonrheumatic mitral valvulopathies].
AB  - The present paper analyzed the indications and surgical treatment in 505 patients
      with lesions of the mitral valve. 350 lesions were of rheumatic nature and 148
      with nonrheumatic etiology. 31 patients with infectious endocarditis with mitral
      localization were operated; 3 deaths and 56 cases wits aggravation of the lesions
      after endocarditis with a mortality of 6%, were recorded. The severity factors,
      the complications and characteristics of the intervention in these patients were
      analyzed. 48 patients had dysfunctions of the mechanical prosthesis with disk and
      11 with Edwards Carpentier's prosthesis. The dysfunction types, the diagnosis
      methods and the evolution were investigated. 16 emergency cases with dysfunctions
      of the prostheses were operated wits good results. The cooperation among
      cardiologist, surgeon, explorer and anesthesiologist is an essential condition
      for the best solution of the new and complex pathology.

PMID- 1978397
TI  - [Cutaneous manifestations of infection due to hepatitis B virus].
AB  - Two entities can precede the clinical and biological signs of hepatitis B virus
      (HBV) infection: the various lesions of the serum sickness-like prodrome
      (urticaria, maculopapular exanthem, purpura, etc.) induced by the deposition of
      intravascular circulating immune complexes and papular acrodermatitis of
      childhood in which the physiopathological role of HBV has not yet been
      established. The persistence of HBs antigen (HBs Ag) may give rise to the
      purpuric lesions of essential mixed cryoglobulinemia and to the livedo, the
      nodules and ulcerations of poly-arteritis nodosa.

PMID- 1978398
TI  - [Physical treatment of post-traumatic algoneurodystrophy of the foot].

PMID- 1978399
TI  - Cytomegalovirus infections: epidemiology, diagnosis and treatment strategies.
      Proceedings of a symposium. Cambridge, Massachusetts. 10-12 November 1988.

PMID- 1978400
TI  - Carrier detection and prenatal diagnosis of haemophilia. Present and future
      strategies.
AB  - The advent of molecular genetics has had a significant impact on carrier
      detection and prenatal diagnosis in the haemophilias. Where phenotypic analysis
      can only identify with varying degrees of probability up to 90% of carriers and
      can only be used in prenatal diagnosis when fetal blood is obtained (18-20 weeks
      gestation), genotypic analysis gives a greater than 99% certainty of carrier
      status (when informative) and allows for prenatal diagnosis at 8-12 weeks
      utilising DNA obtained by chorionic villus sampling. Furthermore, the
      introduction of the technique of polymerase chain reaction (PCR) amplification of
      DNA into genotypic analysis either for the detection of the disease-causing
      defect itself, or to detect an intragenic informative polymorphism, has
      significantly increased the ease by which these procedures can be introduced into
      the laboratory. PCR based family studies in haemophilia will become increasingly
      available in both developed and developing countries. While in the former
      detection of the defect itself will become available, particularly for
      haemophilia B, in other countries simple PCR based DNA polymorphism analysis will
      become the mainstay of effective, practical haemophilia genetics.

PMID- 1978401
TI  - [Lupus erythematosus disseminatus, lesional mechanisms, pathogenesis and
      genetics].
AB  - Systemic lupus erythematosus (SLE) is a model of autoimmune disease. Its study,
      and that of spontaneous murine models, have benefited from new immunological and
      molecular biology techniques. New hypotheses have been put forward to explain the
      mechanisms of SLE lesions. The genetic origin of autoantibodies begins to be
      better known. Auxiliary CD4+ lymphocytes seem to play a capital role in the
      occurrence of lymphocyte abnormalities. The disease is multigenic. Much work is
      currently devoted to the identification and characterization of genetic factors.

PMID- 1978402
TI  - [Hereditary factors of essential arterial hypertension].

PMID- 1978403
TI  - Reflux esophagitis.
AB  - The various therapeutic approaches for reflux esophagitis are to increase the
      competence of the antireflux barrier, to enhance esophageal clearance, to improve
      gastric emptying and pyloric sphincter competence, to coat damaged tissue, and,
      especially, to reduce the volume and pH of gastric contents. Of the prokinetic
      agents, cisapride is the only drug with proven benefit. Single-agent therapy with
      conventional-dose H2-receptor antagonists or sucralfate results in similar
      degrees of symptom relief and healing. Post-evening meal (PEM) dosing of H2
      receptor antagonists appears to be a rational method of suppressing late evening
      gastric acidity, but on balance the symptomatic response of twice daily dosing is
      superior to once daily dosing. More rapid symptom relief and healing are achieved
      with high-dose H2-receptor antagonists and omeprazole. The significance of
      sustained a(hypo)chlorhydria remains to be established. To prolong the
      symptomatic and/or endoscopic remission, the therapy has to be continued long
      term with high-dose H2-receptor antagonist, cisapride either alone or in
      combination with H2-receptor antagonist, or sucralfate with or without H2
      receptor antagonist. In the elderly or complicated patient long-term omeprazole
      may be a justified alternative.

PMID- 1978404
TI  - Taking the tension out of the portal system. An approach to the management of
      portal hypertension in the 1990s.
AB  - The past decade saw the emergence of sclerotherapy and vasoactive pharmacologic
      agents as alternatives to surgery in the prevention and treatment of variceal
      haemorrhage. Despite encouraging results from clinical trials with regard to the
      prevention of rebleeding, these modalities of therapy have made no major impact
      on survival. This failure to alter radically the clinical outcome results from
      the fact that in many patients with cirrhosis death is primarily related to the
      degree of hepatic decompensation rather than the prevention or control of
      variceal bleeding. Advances in our knowledge of vasoactive mediators, receptor
      function, and altered vascular reactivity have provided increased insight into
      the circulatory disturbances that characterise cirrhosis and portal hypertension.
      Earlier and more aggressive pharmacologic intervention with single or combination
      drug therapy may inhibit fibrogenesis, reduce portal vascular resistance, and
      improve liver function and therefore provide effective prophylaxis against
      variceal haemorrhage. The emergence of reliable prognostic indices for variceal
      bleeding should help identify patients at risk who would benefit from prophylaxis
      with either drugs or sclerotherapy. Transplantation will be increasingly
      considered in the patient at high risk of recurrent bleeding before the stage of
      severe hepatic decompensation (the risks of the transplant then become very much
      greater), as the definitive means for reducing mortality in cirrhosis and portal
      hypertension.

PMID- 1978405
TI  - Acid and barriers. Current research and future developments for peptic ulcer
      therapy.
AB  - Medical therapy for peptic ulcer disease has been targeted at inhibiting acid
      secretion based on the belief that ulcers occur due to an imbalance between
      aggressive and protective factors. New antisecretory agents are unlikely to show
      any dramatic improvement over the success and safety of histamine H2 receptor
      antagonists or the recently introduced H+K+ATPase proton pump antagonist
      omeprazole. The development of specific muscarinic M3 and gastrin receptor
      antagonists will provide useful agents to suppress acid and pepsinogen secretion
      by alternative means and may prevent the associated hypergastrinaemia seen with
      anti-secretory therapy. Enhancement of mucosal defence by site protective agents
      will be based on a better understanding of the vascular and immune factors
      involved in maintaining mucosal integrity and the growth factors that regulate
      wound healing. Molecular techniques are likely to produce the 'model anti-ulcer'
      agent which will effectively inhibit acid secretion and also enhance wound
      healing thus providing a cure for this chronic disease.

PMID- 1978407
TI  - XXIII Scandinavian conference of gastroenterology and XIV Scandinavian endoscopy
      meeting, Reykjavik, June 14.-16. 1990. Abstracts.

PMID- 1978406
TI  - Inflammatory bowel disease revisited: newer drugs.
AB  - The development of new drug therapy is an evolutionary process progressing from
      clinical success with current treatments through an understanding of interactions
      in the immune and inflammatory events that culminate in the tissue injury of IBD.
      The basic immunoinflammatory response is reviewed, with identification of the
      recognized and potential sites of activity of current therapies. Potential sites
      and implications for future interventions by newer therapies are discussed as we
      anticipate the discovery of the etiology and eventual cure for ulcerative colitis
      and Crohn's disease.

PMID- 1978408
TI  - [The treatment of ischemia in acute myocardial infarction].
AB  - Rapid reestablishment of myocardial blood supply is the ideal in the treatment of
      acute myocardial infarction. Thrombolysis and, in selected cases, percutaneous
      transluminal coronary angioplasty (PTCA) or coronary bypass surgery may limit the
      extent of myocardial necrosis and improve survival. An open, infarct-related
      artery after thrombolysis carries a better prognosis, but it remains to be
      established whether the persistent lesion needs to be treated by PCTA or surgery
      in all patients. Early intravenous beta blockade reduces inhospital mortality by
      approximately 15% in patients without thrombolysis, while calcium antagonists,
      despite their theoretical promise and in vitro results, are not effective in the
      early phase of acute myocardial infarction. Only diltiazem seems to reduce the
      incidence of reinfarction in patients with non-Q-wave infarction. Aspirin reduces
      mortality in patients with unstable angina pectoris and in patients with acute
      myocardial infarction with or without concomitant thrombolysis.

PMID- 1978409
TI  - Takayasu's arteritis in western South Dakota.
AB  - Takayasu's arteritis is an inflammatory condition affecting the large arteries.
      While most reported cases are from Latin America and the Orient, the disease has
      a worldwide distribution. Patients frequently complain of claudication,
      arthralgias and fatigue, and physical examination is remarkable for vascular
      bruits and pulse deficits. The diagnosis is established by angiography and a
      typical clinical presentation. Prednisone is adequate treatment in the majority
      of patients. Cyclophosphamide and vascular bypass surgery are reserved for more
      severe cases. Two cases identified in western South Dakota are presented followed
      by a detailed literature review.

PMID- 1978410
TI  - Evolving similarities--between disciplines.

PMID- 1978411
TI  - Region-specific neural induction of an engrailed protein by anterior notochord in
      Xenopus.
AB  - Anterior-specific neural induction can be assayed by means of an antibody that
      recognizes the Xenopus homeobox-containing protein En-2. The En-2 antigen is an
      excellent early marker, since it is present as a discrete band in the anterior
      neural plate of neurula embryos. Regional induction was assayed by combining
      dorsal mesoderm with competent ectoderm. Anterior notochord from the early
      neurula induced En-2 frequently, while posterior notochord induced En-2 less
      frequently. Presumptive somitic mesoderm and presumptive head mesoderm, though
      they induced neural tissue, were not strong inducers of En-2. Thus, anterior
      notochord may be the primary mesodermal tissue responsible for the patterning of
      the anterior neural plate.

PMID- 1978412
TI  - Specification of jaw muscle identity in zebrafish: correlation with engrailed
      homeoprotein expression.
AB  - Molecules that determine the specific features of individual muscles in
      vertebrates are unknown. Antibody labeling studies described here revealed a
      molecular difference among muscles in the zebrafish head, in that two
      functionally related jaw muscles (the levator arcus palatini and the dilator
      operculi), and not other head muscles, expressed engrailed-homeodomain proteins.
      Expression began in mesoderm-derived muscle-precursor cells in the paraxial
      mesenchyme and continued during muscle morphogenesis and differentiation. Growth
      cones of trigeminal motoneurons that innervate these muscles associated with the
      precursors within a few hours of the time they began to express engrailed. It is
      proposed that the engrailed proteins in these cells establish muscle identity and
      neuromuscular target recognition.

PMID- 1978414
TI  - Clinical significance of fibrinolysis. XIIth congress of the International
      Society on Thrombosis and Haemostasis. August 1989. Proceedings.

PMID- 1978413
TI  - Correction of a defect in mammalian GPI anchor biosynthesis by a transfected
      yeast gene.
AB  - Glycosylphosphatidylinositol (GPI) serves as a membrane anchor for a large number
      of eukaryotic proteins. A genetic approach was used to investigate the
      biosynthesis of GPI anchor precursors in mammalian cells. T cell hybridoma
      mutants that cannot synthesize dolichol-phosphate-mannose (Dol-P-Man) also do not
      express on their surface GPI-anchored proteins such as Thy-1 and Ly-6A. These
      mutants cannot form mannose-containing GPI precursors. Transfection with the
      yeast Dol-P-Man synthase gene rescues the synthesis of both Dol-P-Man and mannose
      containing GPI precursors, as well as the surface expression of Thy-1 and Ly-6A,
      suggesting that Dol-P-Man is the donor of at least one mannose residue in the GPI
      core.

PMID- 1978415
TI  - Pathogenesis of, and resistance to, neonatal bacterial infection. Proceedings of
      a symposium. Vail, Colorado, June 8-10, 1989.

PMID- 1978416
TI  - [A case of hypogammaglobulinemia associated with polyarteritis nodosa presenting
      a variety of symptoms in childhood].
AB  - A case of polyarteritis nodosa (PN) in childhood involving various organs such as
      the gastrointestinal tract, skin, CNS, kidneys and liver with
      hypogammaglobulinemia is reported. This 6 month old girl was admitted to our
      hospital with vomiting, diarrhea, bloody stools with mucous and weight loss. For
      the past 5 months she had these abdominal symptoms. She was diagnosed as having
      PN of the Kussmaul-Maier variety on the grounds of the biopsy of skin lesion
      where a necrotizing vasculitis was found. Prednisolone and methylprednisolone
      pulse treatment were not effective in suppressing the progress of the disease. At
      the age of 1 year 7 month a combination therapy of prednisolone and
      immunosuppressants (cyclophosphamide) was started and this was found to be
      effective. She was discharged when she was 2 year and 2 month. The dosage of
      prednisolone was tapered as the activity of the PN decreased and she did well
      with a maintainance dosage of 9.5 mg/day. At 3 year 6 month of age she suddenly
      developed hypertension (the plasma renin activity was found to be 16.6 ng/m/hr.
      and the aldosterone 220 ng/dl). CNS involvement such as spinal cord dysfunction,
      left sided convulsions, cerebral hemorrhage developed 5 months later.
      Methylprednisolone pulse therapy was performed 3 times and 2 mg/kg/day of
      prednisolone was administered. In spite of this therapy she passed away with a
      massive cerebral hemorrhage at the age of 4 year 8 month. Unfortunately an
      autopsy was not performed. Results of the immunological tests proved that the
      hypogammaglobulinemia was a common variable immunodeficiency (CVI). It has been
      reported that primary immuno-deficiency syndrome is often associated with
      collagen disease and auto-immune disease. This lack of the defense mechanism
      against the virus or extra antigen could be related to the onset of collagen and
      auto-immune disease. As the correlation between CVI and PN has not been clarified
      this case is of interest as concerns the cause of PN.

PMID- 1978417
TI  - [Adverse reactions of immunomodulatory agents].

PMID- 1978418
TI  - Regulation of adrenergic receptors in intraocular hippocampal transplants: role
      of noradrenergic innervation.
AB  - Hippocampal tissue transplanted into the anterior chamber of the eye offers a
      unique system in which development can be studied in the absence of the
      noradrenergic innervation. This system was used to determine the extent to which
      noradrenergic innervation regulates the development of adrenergic receptors. In
      addition to examining single denervated transplants, transplants grown with
      innervation from the superior cervical ganglia of the host rat or from locus
      coeruleus cotransplants were also examined to determine whether the source of
      norepinephrine and extent of innervation in oculo regulate the development and
      density of adrenergic receptors. In vitro autoradiographic analysis of ligand
      binding to both alpha 1- and beta-adrenergic receptors with 125I-BE 2254 and 125I
      pindolol, respectively, was used to characterize adrenergic receptors in the
      intraocular transplants. Quantitative analysis of the receptors showed an up
      regulation of both alpha 1- and beta-adrenergic receptors in tissue grown in the
      absence of norepinephrine, but in general there was not a high degree of
      correlation between norepinephrine content and receptor density. Although high
      performance liquid chromatography (HPLC) analysis of catecholamines revealed
      higher than normal amounts of norepinephrine in hippocampal transplants
      innervated by the superior cervical ganglia or a locus coeruleus cotransplant,
      the density of alpha 1 and beta receptors was quite comparable with values found
      in the literature for normal adult hippocampus. These results suggest that the
      relationship between receptor number and density of innervation may differ
      significantly from what is observed in response to pharmacological manipulation
      of norepinephrine systems in the adult brain.

PMID- 1978419
TI  - Autoradiographic localization of delta opioid receptors within the
      mesocorticolimbic dopamine system using radioiodinated [2-D-penicillamine, 5-D
      penicillamine]enkephalin (125I-DPDPE).
AB  - The enkephalin analog [2-D-penicillamine, 5-D-penicillamine]enkephalin was
      radioiodinated (125I-DPDPE) and shown to retain a pharmacological selectivity
      characteristic of the delta opioid receptor in in vitro binding studies. The
      distributions of 125I-DPDPE binding, using in vitro autoradiographic techniques,
      were similar to those previously reported for the delta opioid receptor. The
      nucleus accumbens, striatum, and medial prefrontal cortex contain dense gradients
      of 125I-DPDPE binding in regions known to receive dopaminergic afferents
      emanating from the mesencephalic tegmentum. Selective chemical lesions of the
      ventral tegmental area and substantia nigra were employed to deduce the location
      of the 125I-DPDPE binding within particular regions of the mesocorticolimbic
      dopamine system. Unilateral lesions of dopamine perikarya (A9 and A10) within the
      ventral tegmental area and substantia nigra produced by mesencephalic injection
      of 6-hydroxydopamine resulted in significant (20-30%) increases in 125I-DPDPE
      binding contralateral to the lesion within the striatum and nucleus accumbens.
      Lesions of the perikarya (dopaminergic and nondopaminergic) of the ventral
      tegmental area, induced by quinolinic acid injections, caused increases of less
      magnitude within these same nuclei. No significant alterations in 125I-DPDPE
      binding were observed within the mesencephalon as a result of either treatment.
      The specificity of the lesions was confirmed by immunocytochemistry for tyrosine
      hydroxylase. These results suggest that the enkephalins and opioid agonists
      acting through delta opioid receptors do not directly modulate dopaminergic
      afferents but do regulate postsynaptic targets of the mesocorticolimbic dopamine
      system.

PMID- 1978420
TI  - Pharmacology of N-methyl-D-aspartate-induced brain injury in an in vivo perinatal
      rat model.
AB  - Intrastriatal injection of the glutamate analogue N-methyl-D-aspartate (NMDA, 25
      nmol) in postnatal day (PND) 7 rats provides a rapid, sensitive, and reproducible
      assay in which potential neuroprotective strategies against excitotoxic neuronal
      injury can be examined in vivo. Brain injury is quantified 5 days postinjection
      by comparison of the weights of the injected and contralateral cerebral
      hemispheres. Intraperitoneal injections (15 minutes post-NMDA) of competitive and
      noncompetitive NMDA receptor antagonists attenuated the severity of NMDA-induced
      brain injury. The rank order of neuroprotective potency of these antagonists was
      CGS-19755 greater than DOIPG greater than dextromethorphan greater than HA-966.
      Of these compounds only the competitive antagonist CGS-19755 provided complete
      neuroprotection. NMDA-mediated brain injury was also reduced by the specific
      sigma receptor ligands +PPP and haloperidol (35% reduction). In contrast, drugs
      that reduce presynaptic neurotransmitter release (adenosine) or enhance neuronal
      inhibition (baclofen) were not effective against NMDA toxicity. Although all five
      of the anticonvulsants tested limited NMDA-induced seizure activity, only
      carbamazepine reduced NMDA-mediated brain injury (36% reduction). These findings
      extend earlier observations that NMDA receptor antagonists can limit NMDA-induced
      toxicity in vivo and suggest that sigma receptors contribute to the
      pathophysiology of NMDA-mediated brain injury in vivo. Furthermore, NMDA-induced
      seizures and brain injury appear dissociable in this in vivo model. The results
      illustrate important practical limitations of neuroprotection in vivo vs. in
      vitro.

PMID- 1978421
TI  - Anesthetic influences on the basal activity and pharmacological responsiveness of
      nigrostriatal dopamine neurons.

PMID- 1978422
TI  - Long-term potentiation of monosynaptic EPSPs in rat piriform cortex in vitro.
AB  - Induction of long-term potentiation (LTP) by burst stimulation patterned after
      the limbic system theta rhythm was studied in slices of piriform cortex.
      Monosynaptic responses were evoked by stimulation of afferent fibers of the
      lateral olfactory tract (LOT) or the intrinsic associational (ASSN) feedback
      system. LTP was difficult to elicit at LOT synapses in the presence of 2.5 mM
      extracellular Mg2+, and when it was induced potentiation increased for 20-30 min
      after burst stimulation before stabilizing. The probability of inducing LTP was
      increased when the extracellular Mg2+ concentration was reduced to 50 microM. In
      ASSN synapses LTP developed in about 1 min after burst stimulation and then
      remained stable. ASSN system LTP was more readily induced in slices from caudal
      than rostral piriform. Induction of LTP at both LOT and ASSN synapses was blocked
      by D-2-amino-5-phosphonopentanoate, indicating that NMDA receptor activation was
      required. Neither system exhibited the decremental short-term potentiation effect
      observed after burst stimulation of inputs to the CA1 field of hippocampus.

PMID- 1978423
TI  - [Famotidine--a new histamine H2 antagonist].

PMID- 1978424
TI  - Pharmacology of recovery after stroke.
AB  - Laboratory research during the past decade has begun to provide insights into the
      neurobiologic basis of functional recovery after brain injury. It is clear that
      drugs influencing specific neurotransmitters also can influence the recovery
      process. Some of these drugs may be beneficial, but others may be detrimental.
      Some of the difficulties in interpreting the results of these behavioral studies
      are reviewed, and potential mechanisms of drug effects are discussed. These types
      of studies are leading to an increased awareness of the potentially harmful
      effects of some drugs often given to stroke patients. Pharmacotherapy designed to
      enhance functional recovery after stroke may be possible in the future.

PMID- 1978425
TI  - Comparison of RFLP-DR beta and serological HLA-DR typing in 1500 individuals.
AB  - A group of 1522 individuals were HLA-DR-typed both by the standard serological
      technique and by the RFLP method. Whereas 11% (n = 164) of the serological
      typings were technically unsuccessful or doubtful, all typings were successful by
      RFLP. The results of the remaining 1358 typings revealed a serological error rate
      of 25%. In 16% a serological "blank" turned out to be a definable allele by RFLP,
      while in 9% an allele was incorrectly interpreted by serology. Of the individuals
      tested, 11% were HLA-DR homozygous by RFLP. Our results demonstrate an important
      clinical potential of RFLP typing for the typing of bone marrow transplant
      candidates in whom serology often fails, and for kidney transplant candidates
      with "blanks" or serologically "difficult" HLA antigens.

PMID- 1978426
TI  - Czech mouse.

PMID- 1978427
TI  - Post-meiotic gene expression.
AB  - Evolutionary arguments and well-designed experiments (based on false premises,
      however) had suggested that post-meiotic gene expression did not occur in
      animals. The techniques of molecular genetics have now clearly demonstrated such
      genetic activity in mammalian testes. The current problem is to understand why
      some classes of genes, such as Zfy and many oncogenes, are expressed in this
      manner.

PMID- 1978428
TI  - [The effect of phenobarbital, ionol and cAMP on the activity of glutathione
      metabolism enzymes in rodents].
AB  - The phenobarbital and ionol administration to rats and mice increases
      considerably the glutathione transferase, glutathione reductase and gamma
      glutamyl transferase activities in the liver. The induction of these enzymes has
      been observed in a number of experiments in the heart and kidney but it was less
      pronounced. A correlation was established between the induction of glutathione
      transferase, glutathione reductase and gamma-glutamyl transferase, their changes
      in mice and rats, phenobarbital and ionol effects. The stimulatory effect of cAMP
      on glutathione transferase in the liver (and in a number of experiments in the
      heart) increased against a background of the both agents. The cAMP-dependent
      activation of glutathione peroxidase was retained in the heart but in some series
      experiments it disappeared in the liver and kidney. Mechanisms of the long-term
      (induction) and short-term (cAMP) elevation of the glutathione transferase and
      glutathione peroxidase activities functioned independently and often in concord.
      It is suggested that induction of glutathione metabolism enzymes may play an
      important role in biological effects of ionol.

PMID- 1978429
TI  - [Physico-chemical properties of elastase from the sea star Patiria pectinifera].
AB  - An elastolytic protease was purified from the hepatopancreas of the sea star
      Patiria pectinifera with specific activity of 100 units per 1 mg of protein. The
      molecular mass of the enzyme was estimated to be 30 KD by SDS-polyacrylamide gel
      electrophoresis. The isoelectric point of the enzyme was shown to be about 7.3 by
      gel isoelectrofocusing. The pH-dependence of the sea star elastase activity was
      determined toward Z-Ala-pNA. Values of kKaT and KM were equal to 36 s-1 and 1 mM,
      respectively. The kinetics of the thermal denaturation of purified elastase was
      studied at 40 and 60 degrees C. High thermostability and high activity of star
      elastase permit relying upon successful application of the enzyme in production
      of different cell cultures.

PMID- 1978430
TI  - [Adrenoganglioplegia as a method of correction of hemodynamic disorders in
      surgical patients with initial hypotension].
AB  - The possibility to use adreno- and ganglionic blockaders in the operative period
      in surgical patients with initial hypotension is considered. The examinations
      performed in 37 patients have shown that addition of adreno- and ganglionic
      blockaders to routine correcting therapy results in earlier (after premedication)
      and more economical (at the expense of elevation of the initial low peripheral
      vascular resistance) arrest of the initial hypotonia.

PMID- 1978431
TI  - [Density of selected enzymes in the goblet cells of the small intestine in
      piglets experimentally infected with the coccidium Isospora suis].
AB  - The density of selected enzymes in the goblet cells of the mucous membrane of the
      small intestine was studied in a group of 12 gnotobiotic piglets experimentally
      infected with the coccidium Isospora suis one day after parturition (DPP), using
      the Vickers M-786 scanning and integrating microdensity meter. At an infecting
      dose of 100,000 oocysts of I. suis, the histochemistry of the goblet cells of the
      mucous membrane of the piglets changed significantly in the period of 4 to 10
      days after infection (DPI). Increases occur in the density of non-specific
      esterase (EC. 3.1.1.1.) and acid phosphatase (EC. 3.13.2.). The density of acid
      and neutral muco-substances declines and the densities of alkaline phosphatase
      (EC. 3.1.3.1.) and aminopeptidase M (EC. 3.4.11.2) are significantly high. The
      goblet cells of the mid and posterior parts of jejunum are very similar in their
      histochemistry in the experimentally infected gnotobiotic piglets. In the
      duodenum and ileum the histochemical picture of the goblet cells shows no
      substantial difference from the data recorded in the goblet cells of the mucous
      membrane of the small intestine of the four control piglets at an age of two to
      seven days.

PMID- 1978432
TI  - The effects of temik and sumicidin and their mixture on Nubian goats.
AB  - The administration of single oral doses of a mixture of 0.25 mg temik/kg and
      112.5 mg sumicidin/kg to Nubian goats caused severe clinical signs. Death
      occurred within 10 h after redosing on day 7. Lesions were correlated with
      clinical chemistry changes. Goats which received single oral doses of 0.25 mg
      temik/kg or 112.5 mg sumicidin/kg alone has slight clinical changes and recovered
      5 h post-dosing.

PMID- 1978433
TI  - Histology of gastric biopsies from peptic ulcer patients before and after short
      term treatment with omeprazole or H2-receptor antagonists.
AB  - Sixty patients with duodenal or prepyloric ulcers were given omeprazole (30 or 40
      mg o.m.; average period of treatment: 2.9 weeks) or histamine H2-receptor
      antagonists (cimetidine 400 mg b.i.d. or ranitidine 150 mg b.i.d.; average period
      of treatment; 3.5 weeks) for a single period ranging between 2 and 6 weeks. At
      the end of the treatment period fasting plasma gastrin levels were moderately
      increased in both groups in comparison with the pretreatment values. Endoscopic
      biopsies were taken from the oxyntic mucosa at the beginning and at the end of
      the treatment period. Light microscopy of the biopsies was aimed particularly at
      determining the number of endocrine cells. In addition, the mucosal thickness and
      the volume densities of the parietal cells, the lamina propria and the gland
      lumina were measured. There were no significant differences in the endocrine or
      parietal cell populations, between biopsies taken from the patients before and
      after treatment with omeprazole or histamine H2-receptor antagonists. The mucosal
      thickness and the densities of the lamina propria and of the gland lumina
      remained unaffected by the treatment.

PMID- 1978434
TI  - Principal lymphocyte subpopulation in local host response to human oesophageal
      cancer.
AB  - We investigated what subpopulations of tumour-infiltrating lymphocytes (TIL) play
      a key role in in vivo function and what determines the degree of local host
      response represented by lymphocyte infiltration in human oesophageal cancer. We
      examined the increased subpopulation of TIL in "good responders" (GR) (patients
      with intensively TIL infiltrated tumours) when compared with "poor responders"
      (PR) (patients with weakly TIL infiltrated tumours). The frequency of each
      subpopulation was determined by quantitative flow-cytometric measurement on TIL
      separated from fresh tumours. Of TIL in GR, the frequency of CD3+ cells increased
      significantly (P less than 0.05) but the frequencies of CD16+, Leu7-, and CD16+
      Leu7- cells were low and did not increase significantly compared with those in
      PR. With respect to T-cell subsets of TIL in GR, the frequency of CD8+ cells was
      significantly higher than that in PR (P less than 0.01), and CD4+/CD8+ ratio was
      lower than that in PR (P less than 0.025). On two-colour analyses, most of CD8+
      cells (cytotoxic/suppressor T-cells: Tc/s) did not co-express CD11b and the
      frequency of CD8+ CD11b- cells (cytotoxic T-cell: Tc) increased significantly
      compared with that in PR. Clinicopathological and phenotypic analysis of
      peripheral blood lymphocytes revealed that there are no major differences in
      general immunocompetence between GR and PR. These results suggest that Tc/s,
      especially Tc, might play a key role in local host response. They also suggest
      that not only the general immune status of the host but also the identification
      of class I major histocompatibility complex antigens by the host at the tumour
      site may strongly affect the degree of host response in oesophageal cancer.

PMID- 1978435
TI  - Immunohistological characteristics of the infiltrating lymphoid cells and
      expression of HLA class I and II antigens in nasopharyngeal carcinoma.
AB  - The immunohistological characteristics of infiltrating lymphoid cells and the
      expression of human leucocyte antigens class I and II (HLA-ABC and HLA-DR,
      respectively) were studied in 50 pre-treatment nasopharyngeal carcinomas. The
      majority of lymphoid cells were activated lymphocytes expressing thymocyte OKT10
      marker. CD4+ cells (T-helper/inducer) out-numbered CD8+ cells (T
      suppressor/cytotoxic) by at least two- to four-fold. CD22+ cells (pan-B
      lymphocytes) were scanty in the peri-tumoral areas and were absent in 29 out of
      50 biopsies. A moderate number of cells expressing CD15 (monocytes/macrophages)
      were also detected. CD16+ cells (natural killer cells) were found to be sparse or
      absent. Expression of HLA class I and II antigens on the tumor cells in 35
      biopsies was variable. HLA-ABC staining was intense in 6, reduced in 13 and
      partially lost in 16, whereas staining of HLA DR was intense in 7, reduced in 11
      and partially lost in 17. Full expression of both antigens was demonstrable in
      only 2 biopsy samples. The expression of HLA antigens in the tumour had no
      relationship to the type or degree of lymphocytic infiltration or staging of the
      tumour.

PMID- 1978437
TI  - Decreased binding of HIV-1 and vasoactive intestinal peptide following plasma
      membrane fluidization of CD4+ cells by phenytoin.
AB  - Plasma membrane fluidity of intact peripheral blood lymphocytes (PBL) of
      phenytoin-treated nonepileptic patients and phenytoin-treated CD4+ lymphoid cells
      H9 and K37 was determined by fluorescence anisotropy measurements. Anisotropy
      values of the membrane probe 6-(9-anthroyloxy) stearic acid were decreased in all
      cell types as compared with controls, indicating increased plasma membrane
      fluidity of phenytoin-treated cells. Specific binding of 125I-labeled vasoactive
      intestinal peptide (VIP) to its cellular receptor CD4 on PBL was decreased in PBL
      of phenytoin-treated patients as compared with untreated, healthy subjects.
      Adsorption of a different ligand to the CD4 receptor on PBL, the human
      immunodeficiency virus type 1 (HIV-1), was likewise abolished to PBL of phenytoin
      treated patients and phenytoin-treated CD4+ H9 and K37 cells, as assessed by
      indirect immunofluorescence. Subsequent HIV-1 infection of phenytoin-treated H9
      and K37 cells was reduced as measured by indirect immunofluorescence and p24
      antigen production. These data indicate that CD4 receptor availability for VIP
      and HIV-1 was reduced in phenytoin-treated cells. Using the DNA-specific dye
      Hoechst 33258, we examined cell cycle phase distributions of HIV-1 adsorbing and
      nonadsorbing H9 cells, as separated by flow cytometry. The majority of HIV-1
      adsorbing cells were found to be in the G2/M phase, while nonadsorbing cells were
      mainly in the G0/G1 phase, during which plasma membrane fluidity is supposed to
      be increased. This study indicates that plasma membrane fluidization by phenytoin
      may serve to disrupt CD4 receptor function and emphasizes the impact of plasma
      membrane properties on HIV-1 adsorption and infection.

PMID- 1978436
TI  - Inflammatory abdominal aortic aneurysms: a disease entity? Histological analysis
      of 60 cases of inflammatory aortic aneurysms of unknown aetiology.
AB  - Sixty inflammatory aortic aneurysms of unknown aetiology were examined by serial
      sections. The histological findings failed to reveal significant differences in
      either thoracic or abdominal aneurysms with or without marked adventitial
      fibrosis. Their identical morphology does not favour the existence of a special
      disease entity of so-called inflammatory abdominal aortic aneurysms (IAAA).
      Absence or existence of giant cells of any type, occurrence of plasma cells,
      eosinophils, granulomas, fibrinoid necrosis and adventitial fibrotic thickening
      cannot be considered as variables which help in differentiation. IAAA are
      characterized by a marked predominance of male patients and a rather benign
      clinical course. They usually affect the age group around 60 years. They are not
      rare and do not seem to be restricted to certain races. Their aetiology, like
      that of the cases affecting the thoracic aorta (Takayasu's disease, non-specific
      aortitis) remains unknown, although autoimmune diseases, the retroperitoneal
      fibrosis of Ormond and arteriosclerosis may be related. However, on the basis of
      the present evidence we cannot consider them to be one of these diseases. There
      are no morphological findings which would justify the separation of IAAA from
      Takaysu's disease.

PMID- 1978438
TI  - [Hemorrhagic fever with renal syndrome in Yugoslavia 1951-1988].
AB  - Data on hemorrhagic fever with renal syndrome (HFRS) incidence in SFRY 1950-1988
      were analysed. Information sources were published papers and official reports of
      Federal and Republic Institutions for Public Health. Indirect immunofluorescence
      technique was used in testing 1.842 organs of small wild mammals to the presence
      of HFRS viral antigen. This antigen was found in the lungs of 11 species. Average
      incidence of the carrier state was 10.4% Registered were 613 cases within the
      period 1951-1988. Morbidity rate was 0.05-10.6:1.00.000 for years. Disease have
      been registered during the whole year with maximum incidence rate in summer
      months. Men most capable of working were the most frequently affected: farmers,
      wood workers, soldiers. Average lethality was 5.2%.

PMID- 1978439
TI  - [Component of kinin system, blood histamine and serotonin in patients with
      hemorrhagic fever with renal syndrome].
AB  - Hyperhistaminemia, hyperserotoninemia and activation of the kinin system followed
      by a decrease in the system reverse capacities and inadequate compensatory
      reactions were detected in 86 patients with various forms of hemorrhagic fever
      and renal syndrome. The data obtained suggest that these biologically active
      substances are of importance in pathogenesis of the disease.

PMID- 1978440
TI  - [The effect of narcotic analgetic fenaridine and narcotic antagonist FI on the
      level of cyclic nucleotides in the brain of albino rats].
AB  - Content of cAMP and cGMP was estimated in rat brain corpus striatum after
      treatment with narcotic analgetic fenaridin and antagonist of narcotic analgetics
      F1 which are similar chemically. Various concentrations of fenaridin increased
      the cAMP content, whereas that of cGMP was not altered. At the same time,
      administration of the antagonist of narcotic analgetics F1 led to an increase in
      content of cGMP and to a distinct elevation of cAMP content.

PMID- 1978441
TI  - [Relation between human platelet aggregation and activation of soluble platelet
      guanylate cyclase].
AB  - Guanylate cyclase from thrombocytes with elevated ability to aggregation
      (diabetes mellitus) exhibited a decreased rate of activity and low response to
      stimulation by sodium nitroprusside and protoporphirin IX. The phenomenon
      observed did not depend on hem-deficiency of guanylate cyclase and was manifested
      most distinctly in the II type of diabetes mellitus as compared with the I type
      of the disease. Experimental data as well as the previously obtained results
      about more elevated rate of thrombocytes aggregation in patients with the II type
      of diabetes mellitus demonstrated that regulating functions of the cGMP system in
      the cells aggregation were impaired and that aggregation of thrombocytes appears
      to depend on the guanylate cyclase activity.

PMID- 1978442
TI  - [The effect of liposomes on the hormonal induction of liver tyrosine
      aminotransferase in an experiment].
AB  - Liposomes prevented the hydrocortisone-produced induction of tyrosine
      aminotransferase in animal liver tissue under conditions of normal state and of
      alcohol intoxication. The inhibitory effect of liposomes appears to be mainly
      based on their ability to incorporate into hepatocyte membranes, due to which the
      membrane permeability towards hydrocortisone was altered.

PMID- 1978443
TI  - High-dose intravenous immunoglobulins in HIV-1-infected adults with AIDS-related
      complex and Walter-Reed 5.
AB  - The influence of high-dose intravenous immunoglobulins (HD-IVIG) on the clinical
      status and T4 cell count of adults with AIDS-related complex (ARC) and Walter
      Reed 5 (WR5) was evaluated in a randomized double-blind longitudinal study.
      Inclusion criteria were: (1) T4 cells less than 400/microliters and (2a) oral
      thrush or cutaneous anergy or (2b) two clinical ARC criteria (fever, diarrhea,
      weight loss, fatigue, night sweats). Thirty patients [28 males, 2 females, median
      age 41 (24-64) years] with ARC (n = 8), WR5 (n = 12) and both (n = 10) were
      stratified according to their T4 cell count (greater than or equal to vs. less
      than 300/microliters). Fifteen patients received 0.4 g/kg body weight IVIG and 15
      placebo (albumin 0.03%) every other week for 26 weeks with follow-up for another
      26 weeks. The clinical status was defined as a score consisting of fever,
      diarrhea, night sweats, fatigue, weight loss, oral candidiasis and mucosal or
      cutaneous herpes simplex. Clinical examination and routine laboratory assessments
      were performed before initiation of the study and before each administration,
      lymphocyte phenotyping every 4 weeks and cutaneous reaction, serology and
      lymphocyte stimulation every 12 weeks. Both groups were comparable in initial
      clinical symptoms and laboratory values. Seven patients developed AIDS (treatment
      group: 3, placebo group: 4), 1 patient died by homicide. After 26 weeks, the
      clinical score (particularly fatigue and fever) was significantly improved in the
      treatment group, while the T4 cell count and other clinical and immunological
      parameters remained unaltered. This limited effect was still evident at
      termination of the study after 52 weeks. In conclusion, HD-IVIG can improve the
      clinical status of patients with advanced HIV-1 infection without obviously
      correcting the underlying impaired cellular immunity. The substitution of intact
      antibodies in the state of functional hypogammaglobulinemia is suggested as
      possible therapeutic mechanism.

PMID- 1978444
TI  - [The neurohumoral regulation and energy support of the myocardium in patients
      with heart rhythm disorders].
AB  - Diagnostic electrocardiostimulation (ECS) of the right atrium with evaluation of
      the functional state of the heart conduction system and coronary reserve was
      carried out in 177 patients. The level of blood catecholamines, activity of
      cholinesterase and content of destroyed acetylcholine, cortisol, free fatty
      acids, glucose, insulin, thyroxine, triiodothyronine, renin, testosterone,
      calcium was determined before and at the height of diagnostic ECS. In cases with
      a tendency to bradycardia one could note compensatory tension of the sympathetic
      adrenal system and mechanisms of general adaptation. In organic weakness of the
      sinus node with stable bradysystole there were signs of exhaustion of the adrenal
      reserves of catecholamines and cortisol manifested in paradoxic reduction of them
      in the blood in response to frequent ECS and corresponding changes of energy
      provision.

PMID- 1978445
TI  - [The production of cyclic nucleotides, cyclases and prostaglandins in patients
      with chronic enteritis].
AB  - A study of adenylatecyclase (AC), guanylatecyclase (GC), cAMP, cGMP in the small
      intestine mucosa and PGE2 and PGP2 in the blood serum of 34 patients with chronic
      enteritis showed that development of the malabsorption syndrome, diarrhea,
      structural changes of the small intestine mucosa is influenced by changes in the
      PGE-AC-cAMP and PGP-AC-cGMP systems. Thus, average-severe and severe course of
      the disease was accompanied by an increase in the biopsy material of the small
      intestine mucosa of AC, GC, cAMP, cGMP and PGP2 in the blood.

PMID- 1978446
TI  - [Paralytic ileus as an initial manifestation of malignant VIPoma of the pancreas-
      case report with review of the literature].
AB  - A 57-year old patient with a paralytic ileus of unknown origin was admitted to
      the intensive care unit. Because of the laboratory findings with therapy
      resistant hypokalemia, hypercalcemia and metabolic acidosis a VIPoma was
      suspected. Therapy with somatostatin resulted in correction of laboratory
      abnormalities and in normalization of gastrointestinal motility. Plasma
      concentrations of VIP and PP were elevated, ultrasonography revealed a pancreatic
      tumor. Postsurgical examination of the removal tumor tissue confirmed the
      diagnosis of a malignant VIPoma. Clinical symptoms, laboratory findings with and
      without somatostatin-therapy and immunhistochemical properties are described.

PMID- 1978447
TI  - The representational bias of acquired memory processes.
AB  - The notion that some memory processes are acquired has been around for at least
      two thousand years. However, acquired memory processes have been made the object
      of scientific investigation in only the past two decades. Traditionally,
      psychologists have assumed that acquired memory processes are equally effective
      across the entire range of memory tasks. This article reviews research that has
      investigated whether these processes are equally effective across tasks or are
      more effective for just certain tasks. The review indicates that most, if not
      all, acquired memory processes are biased to deal effectively just certain kinds
      of mental representation. The article proposes that these processes are
      representationally biased because (1) they activate basic memory processes (e.g.
      imagery, rehearsal) which themselves are biased to process certain
      representational attributes and because (2) their use of basic processes follows
      a sequence required by particular memory tasks. Increased understanding of the
      representational bias of acquired processes may be seen to enable better control
      of memory performance and to foster more powerful investigations of memory
      phenomena.

PMID- 1978448
TI  - [The brain mediator systems and the mechanisms of the formation of extinction
      inhibition].

PMID- 1978449
TI  - [Renal microaneurysms in necrotizing vasculitis--incidence in autopsy and
      clinical value].
AB  - Histological renal sections of 24 autopsied patients were evaluated for ectasias
      with greater than or equal to 2 mm diameter that corresponded to "microaneurysms"
      of radiologic nomenclature. Such renal "microaneurysms" of smaller and medium
      sized arteries were seen in 7/9 patients with periarteritis nodosa, 6/10 patients
      with secondary vasculitides and 1/5 patients with Wegener's Granulomatosis. Lumen
      ectasias in acute or subacute lesions of smaller and medium sized arteries were
      caused by fibrinoid necrosis of the arterial walls. Destruction of intimal
      elastic fibres and scar tissue within the arterial wall resulted in real
      aneurysmatic ectasias. Generalised, aggressive, necrotizing vasculitides show the
      highest frequency of microaneurysms. In that cases angiography can frequently
      establish the definite diagnosis by demonstration of microaneurysms.

PMID- 1978450
TI  - Direct mixed antiglobulin reaction (MAR) test in semen at follow-up after
      testicular biopsy of maldescended testes operated in puberty.
AB  - In thirty patients bilateral orchiopexy was performed in puberty. At the
      operation twenty-five patients underwent bilateral testicular biopsies, and five
      patients underwent unilateral biopsies only. In adulthood the semen was analysed
      for antisperm antibodies by the direct mixed antiglobulin reaction (MAR) IgG
      test. In none of the cases a positive direct MAR IgG test was found.

PMID- 1978452
TI  - [Reports of the meetings of the 11th Congress of Gynecologists of the German
      Democratic Republic. Leipzig, December 6-9, 1989. Proceedings].

PMID- 1978451
TI  - [Laser welding of dental ceramic materials].

PMID- 1978453
TI  - [The effect of the adhesion pili of Yersinia pestis on the physiological activity
      of the leukocytes and macrophages in experimental animals].
AB  - The data on the influence of the preparation of Y. pestis adhesion pili on
      peritoneal macrophages in white mice and guinea pigs are presented. Y. pestis
      adhesion pili have been found to induce the dose-dependent increase of cell
      chemiluminescence. They have also been found to induce a number of biochemical
      changes in target cells: the secretion of myeloperoxidase, an increase in the
      activity of cAMP-dependent protein kinases.

PMID- 1978454
TI  - [Antibodies which block thyroid function: current concept of thyroid
      autoimmunity].

PMID- 1978455
TI  - Gastrointestinal decontamination for acute poisoning.
AB  - Acute poisoning remains a common cause of morbidity and even mortality in
      children and adults. The goal of gastrointestinal decontamination is to eliminate
      or to reduce the potentially life-threatening effects of the ingested poison.
      Methods of gastrointestinal detoxication in case of acute poisoning, such as
      induced emesis, gastric lavage, administration of activated charcoal and
      intestinal cleansing are discussed. As far as induced emesis is still concerned,
      only the administration of Ipecac-syrup can be retained. The controversy between
      emesis and gastric lavage still remains. For those toxins well adsorbed by
      activated charcoal, the administration of activated charcoal, followed or not by
      gastric lavage, is the treatment of choice. Single doses of activated charcoal
      can be insufficient. In certain kinds of poisoning, repeated doses of activated
      charcoal are advisable because of the interruption of the entero-hepatic and
      entero-enteric circulation. The benefit and the indications for intestinal
      cleansing in case of acute poisoning seem to be very limited.

PMID- 1978456
TI  - Particularities in children poisoning.
AB  - Poisoning in childhood mostly by ingestion of toxics, remains a frequent and
      potentially severe accident. They are generally avoidable and preventive programs
      should be reinforced. The action of the centre antipoison (CAP) in this field
      must be encouraged. Methods of emergency gastrointestinal decontamination are
      presented. It should facilitate the acute management of children suffering from
      poisoning by ingestion. Carbon monoxyde poisoning is very frequent and more
      severe than we usually think because it induces various sequellae. We developed a
      prospective study to determine the occurrence of unsuspected carbon monoxyde
      poisoning in children presenting a variety of symptoms.

PMID- 1978457
TI  - Simultaneous measurement of TSH-binding inhibitor immunoglobulin and thyroid
      stimulating autoantibody activities using cultured FRTL-5 cells in patients with
      untreated Graves' disease.
AB  - A new and practical assay was developed using cultured FRTL-5 cells for
      simultaneous assessment of TS-ab and TSH-binding inhibitor immunoglobulin,
      allowing direct comparison of these two activities under the same conditions.
      Subsequent to the TS-ab assay in which extracellular cAMP concentration in Hanks'
      medium without NaCl was determined, [125I]b TSH in this medium was added to
      observe the ability of serum Ig to inhibit the binding of [125I]b TSH to FRTL-5
      cells. We found a much higher specific binding of [125I]b TSH to FRTL-5 cells and
      a much greater inhibition of [125I]bTSH binding to the cells exposed to Graves'
      Ig in hypotonic NaCl-free than in NaCl containing Hanks' medium, indicating that
      the binding of both TSH and Graves' Ig to the TSH receptor was salt-sensitive.
      The inhibitory activity of [125I]bTSH binding to the cells was 0.2 +/- 4.6% (mean
      +/- SD) in 45 normals. Inter-assay coefficients of variation in two positive
      controls with the mean values of 18.0 and 65.8% were 15.8 and 16.5%,
      respectively. Among 46 patients with untreated hyperthyroidism owing to Graves'
      disease, 45 (97.8%) were positive for TS-ab; 35 (76.1%) and 40 (87.0%) were
      positive for TSH-binding inhibitor in Ig assays using FRTL-5 cells and
      solubilized porcine thyroid membranes, respectively. TS-ab activities correlated
      less closely with TSH-binding inhibitory activities determined using FRTL-5 cells
      (r = 0.576, p less than 0.001) than with those determined using porcine thyroid
      membranes (r = 0.745, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1978458
TI  - Insulin, glucagon, somatostatin, and thyrotropin-releasing hormone content and
      secretion by perifused fetal rat islets during culture.
AB  - In the neonatal period of the rat, pancreatic thyrotropin-releasing hormone
      content decreases and the sensitivity of insulin secretion to glucose increases.
      In adult rat islets, TRH inhibits glucose-induced insulin release. The aim of
      this study was to investigate whether a high TRH content and release can be part
      of the explanation for the functional immaturity of neonatal islets. For that
      purpose, we have measured the tissue content and the secretion of immunoreactive
      insulin, glucagon, somatostatin and TRH in islets from 21.5-day-old rat fetuses
      cultured for up to one week. Insulin, glucagon and somatostatin content increased
      during one week of culture in the presence of 11.1 mmol/l glucose. The TRH
      content decreased during culture, but did not equal adult values. Insulin,
      glucagon and somatostatin responses to glucose were present after one week of
      culture. Glucose had no effect on TRH release in cultured fetal islets, but
      inhibited TRH release in adult islets. We conclude that glucose can stimulate
      insulin secretion without inhibiting TRH release, but that a decrease in islet
      TRH content and a sensitization of TRH secretion to glucose may be important in
      the full maturation of fetal pancreatic islets.

PMID- 1978460
TI  - Proceedings of the Sixth International Congress on Twin Studies. Rome, 28-31
      August 1989.

PMID- 1978459
TI  - Changes in thyroid volume during antithyroid drug therapy for Graves' disease and
      its relationship to TSH receptor antibodies, TSH and thyroglobulin.
AB  - Changes in thyroid volume during antithyroid drug therapy for Graves' disease
      compared with circulating thyroid parameters were evaluated. One hundred and
      forty-four patients with Graves' disease were treated with methimazole. Thyroid
      volume was measured by ultrasonography (thyroid volume = pi abc/6, where a is
      length, b width, and c depth). Serum TSH, TSH-binding inhibitory immunoglobulins,
      thyroid-stimulating antibodies, thyroglobulin, antimicrosomal antibodies, and
      antithyroglobulin antibodies were also measured. In the whole group of patients,
      thyroid volume correlated significantly with thyroglobulin (p less than 0.01) and
      TSH-binding inhibitory immunoglobulins (p less than 0.01), but not with TSH,
      antimicrosomal antibodies, and antithyroglobulin antibodies. Furthermore, a
      positive correlation was found between thyroglobulin and TSH-binding inhibitory
      immunoglobulins (p less than 0.01). In 11 patients the mean thyroid volume
      decreased significantly after one year of therapy (p less than 0.01), associated
      with decreasing levels of serum TSH-binding inhibitory immunoglobulins. Ten
      patients experienced transient hypothyroidism with an overdose of methimazole,
      and the mean thyroid volume increased significantly (p less than 0.01) with
      increasing serum TSH levels. In conclusion, it is suggested that TSH receptor
      antibodies may have a thyroid growth-stimulating effect. In addition, circulating
      thyroglobulin levels reflect thyroid volume in Graves' disease.

PMID- 1978461
TI  - Expression and functions of P-glycoprotein (mdr1 gene product) in normal and
      malignant tissues.
AB  - This paper describes the cellular and tissue distribution of P-glycoprotein (P
      GP) (mdr1 gene product), the role of P-GP in vivo and immunodiagnosis of multi
      drug-resistant cancers. We mainly used MRK 16 monoclonal antibody (MAb) reactive
      with P-GP. P-GP was found to be expressed very strongly in the adrenal cortex of
      adults and strongly in the renal tubules of the kidney, capillary blood vessels
      of the brain, and also in placenta. Interestingly, P-GP was not distributed in
      fetal and neonatal adrenals, and thus may be closely related to adrenal
      maturation. A high level of P-GP expression was also seen in all cases of
      functional hormone-producing adrenal tumor, one case of insulinoma, two cases of
      untreated colonic cancer, one case each of untreated lung cancer, gastric cancer
      and breast cancer, six cases of renal cell carcinoma and 17 cases of bladder
      cancer. Using flow cytometry and immunocytochemistry, we investigated the
      reactivity of MRK 16 MAb with peripheral human mononuclear cells (mainly blastic
      cells and lymphocytes) from 31 patients with leukemia or malignant lymphoma.
      Reactivity with MRK 16 MAb was observed in five cases. Some cases reflected the
      prior administration of adriamycin, vincristine and VP-16, which are known to
      induce P-GP expression. P-GP-MRK 16-protein A-Sepharose complex derived from
      human adrenal possessed marked ATPase activity. These data suggest that P-GP may
      play a physiological role in the human adrenal. Finally, diagnostic criteria of
      multi-drug-resistant cancers are presented.

PMID- 1978463
TI  - [Chemical constituents and biological activity of plants of the Taxus genus].

PMID- 1978462
TI  - [Application of mouse tail artery for the study of alpha adrenoceptor agonists
      and antagonists and calcium antagonists].
AB  - Isolated mouse tail artery strip was used for the study of alpha 1-, alpha 2
      adrenoceptor agonists and antagonists. NA (alpha 1 and alpha 2 agonist) was shown
      to have greater activity in contracting tail artery. Phenylephrine (alpha 1
      agonist) and clonidine (alpha 2 agonist) exhibited the same contractile action
      but much weaker than NA. Prazosin (alpha 1 antagonist) and yohimbine (alpha 2
      antagonist) greatly diminished the contraction induced by phenylephrine and
      clonidine. These results indicate that mouse tail artery is rich in postsynaptic
      alpha 1- and alpha 2-adrenoceptor. In addition, mouse tail artery preparation was
      shown to be a useful tool for screening calcium agonists and antagonists. This
      model has advantages of being simple and easy to prepare, short equilibrium time
      and more economic in comparison with the helical strips of isolated rat tail
      artery.

PMID- 1978465
TI  - The prolonged benzodiazepine withdrawal syndrome: anxiety or hysteria?
AB  - In an attempt to establish whether prolonged withdrawal symptoms after stopping
      intake of benzodiazepines is caused by return of anxiety, hysteria, abnormal
      illness behaviour or the dependence process itself producing perhaps a prolonged
      neurotransmitter imbalance, a group of such patients suffering prolonged
      withdrawal symptoms (PWS) was compared on a range of psychophysiological measures
      with matched groups of anxious and conversion hysteria patients and normal
      controls. It was found that the psychophysiological markers of anxiety were not
      marked in the PWS group; nor were the averaged evoked response abnormalities
      found to be associated with cases of hysterical conversion in evidence. The PWS
      group were hard to distinguish from normal controls on the basis of
      psychophysiological measures and thus it was felt to be unlikely to be an
      affective disturbance. It was concluded that PWS is likely to be a genuine
      iatrogenic condition, a complication of long-term benzodiazepine treatment.

PMID- 1978466
TI  - Development of a new antipsychotic Remoxipride. Proceedings of an international
      symposium. Monte Carlo, Monaco, June 19-20, 1989.

PMID- 1978464
TI  - Cholinergic mechanisms involved in release and effect of prostaglandin E2 in HCl
      stimulated duodenal HCO-3 secretion in the conscious rat.
AB  - Using a proximal duodenal loop in conscious rats, we investigated interactions
      between prostaglandin E2 and nicotinic and muscarinic receptor mechanisms
      previously found to be involved in the duodenal HCO3- response to HCl. In
      previous studies using the same model, a 5-min perfusion of the duodenal loop
      with 150 mmol l-1 HCl produced a marked and sustained HCO3- response. In the
      present study, the identical challenge produced a rapid 20-fold increase in the
      luminal output of prostaglandin E2 during acid exposure, followed by a sustained
      more than twofold elevation above the basal level during the 45 min monitored.
      The prostaglandin synthesis inhibitor indomethacin (4 mg kg-1 i.p.) suppressed
      the output of prostaglandin E2 during the HCl challenge from 131 +/- 84 to 15.4
      +/- 10.0 pmol cm-1 h-1, and in the post-stimulatory period from 17.3 +/- 9.1 to
      4.4 +/- 2.2 pmol cm-1 h-1. The nicotinic receptor antagonist hexamethonium (20 mg
      kg-1 i.v.) had no effect on the output of prostaglandin E2. The muscarinic
      receptor antagonist atropine (0.5 mg kg-1 s.c.) had no effect on the output of
      prostaglandin E2 during HCl challenge, but reduced the post-stimulatory output to
      7.7 +/- 4.1 pmol cm-1 h-1. Perfusion of the duodenal loop with 0.1 mmol l-1
      prostaglandin E2 produced a HCO3- response that was abolished by hexamethonium
      (20 mg kg-1 i.v.), but not affected by atropine (0.5 mg kg-1 s.c.).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1978467
TI  - A double blind comparative multicentre study of remoxipride and haloperidol in
      schizophrenia.
AB  - Seventy-two patients fulfilling the DSM-III criteria for schizophrenia and
      schizophreniform psychosis were admitted to a multicentre, double-blind
      controlled study to evaluate the efficacy and safety of remoxipride in comparison
      to haloperidol. The mean daily dose of remoxipride at the end of treatment was
      353 mg and of haloperidol, 11 mg. Patients were assessed each week on the Brief
      Psychiatric Rating Scale (BPRS), the Clinical Global Impression (CGI) and the
      symptoms checklist. No significant differences in efficacy were found between the
      two treatments. The median total BPRS score in the remoxipride group was 25 at
      start of active treatment and 17 at the last valid rating (n = 31). For the
      haloperidol group the corresponding figures were 24 and 15 (n = 29). According to
      the CGI, 40% of remoxipride patients and 50% of haloperidol patients were much or
      very much improved. Treatment-emergent extrapyramidal symptoms, such as akathisia
      and rigidity, occurred significantly more frequently, and were more severe during
      treatment with haloperidol than with remoxipride (p = 0.012 and 0.024,
      respectively). Haloperidol-treated patients reported significantly more
      drowsiness and increased sleep during treatment (p = 0.026 and 0.012,
      respectively). No statistically significant differences were seen in endocrine or
      autonomic symptoms. Remoxipride seemed to be as effective as haloperidol, had a
      lower frequency of side effects, and was used safely in the dose range 150-600
      mg/day.

PMID- 1978468
TI  - A double-blind comparative study of remoxipride and haloperidol in acute
      schizophrenia.
AB  - Seventy-one patients were entered into a multicentre, double-blind randomized
      study to compare the efficacy and safety of remoxipride with those of haloperidol
      in the acute treatment of schizophrenia or schizophreniform disorder. The
      patients, who were well-matched regarding demographic characteristics, were aged
      18-64 years. Four patients in the remoxipride group and 6 in the haloperidol
      group discontinued treatment prematurely. The mean daily doses during the last
      week of treatment were 363 mg remoxipride and 9 mg haloperidol. At this time 22%
      of patients on remoxipride and 66% of those on haloperidol were taking
      anticholinergics (p less than 0.001). The clinical efficacy was similar in both
      groups as judged by Present State Examination (PSE) profile and Brief Psychiatric
      Rating Scale (BPRS) ratings. Several adverse symptoms occurred significantly more
      frequently during treatment with haloperidol than with remoxipride, particularly
      where extrapyramidal symptoms were concerned. No clinically relevant changes
      occurred in the laboratory tests in either group.

PMID- 1978470
TI  - Remoxipride and haloperidol in the acute phase of schizophrenia: a double-blind
      comparison.
AB  - The efficacy and safety of remoxipride in the treatment of schizophrenia were
      compared with those of haloperidol in a multicentre double-blind 6-week study
      which was randomized with a parallel group design and was preceded by a washout
      period. Eighty-nine consecutively admitted men and women meeting the Research
      Diagnostic Criteria for schizophrenia in an acute phase of the illness were
      treated with remoxipride 75-300 mg twice daily or haloperidol 5-20 mg twice
      daily. The efficacy assessments were the Brief Psychiatric Rating Scale,
      Krawiecka Rating Scale, and Clinical Global Impression. Both antipsychotic drugs
      produced clinical improvement with no significant differences between the
      efficacy of the two drugs. There were relatively few side effects. There were
      significantly fewer extrapyramidal symptoms and instances of blurred vision with
      remoxipride and less constipation with haloperidol. The results indicate that
      remoxipride is as effective an antipsychotic as haloperidol. Remoxipride has an
      advantage over haloperidol in respect to extrapyramidal side effects.

PMID- 1978469
TI  - A placebo-controlled clinical trial of remoxipride and chlorpromazine in newly
      admitted schizophrenic patients with acute exacerbation.
AB  - We carried out a four-week double-blind placebo-controlled study comparing
      remoxipride (n = 20) to chlorpromazine (n = 21) and placebo (n = 21) in the
      treatment of newly admitted schizophrenic patients with acute exacerbation.
      Chlorpromazine was found to be significantly better than remoxipride on the
      dropout rate due to inefficacy, Clinical Global Impression (CGI) of severity of
      illness and Brief Psychiatric Rating Scale (BPRS). Chlorpromazine tended to be
      better than placebo on the dropout rate related to inefficacy, Nurse's Global
      Impression (NGI) of severity and on the BPRS measures of positive symptoms
      (hallucinatory behaviour and thinking disturbance factor). We were unable to
      detect a difference between remoxipride and placebo except that remoxipride was
      better in patients who had previously responded well to neuroleptics. Both drugs
      induced significantly more parkinsonism than placebo, but differently so:
      chlorpromazine induced both types of parkinsonism hypo- and hyper-kinetic
      symptoms, whereas remoxipride induced hyperkinetic symptoms. Chlorpromazine
      caused more tachycardia, drowsiness, orthostatic dizziness, and dry mouth than
      the other two treatments, while patients on remoxipride suffered more from
      insomnia than those on the other two treatments.

PMID- 1978471
TI  - A double-blind multicentre study comparing remoxipride, two and three times
      daily, with haloperidol in schizophrenia.
AB  - A double-blind multicentre study comparing the efficacy and safety of remoxipride
      in relation to haloperidol was conducted in 160 inpatients with schizophrenic
      illness diagnosed according to DSM-III. The study period was 4 weeks. The mean
      daily dose of remoxipride (whether given twice or three times daily) during the
      last week of treatment was 395 mg; the corresponding dose of haloperidol was 17
      mg per day. No significant difference in therapeutic efficacy was found; Brief
      Psychiatric Rating Scale (BPRS) median total scores dropped from 41 to 20
      (remoxipride twice daily, n = 51), 43 to 20 (remoxipride three times daily, n =
      44) 40 to 19 (haloperidol three times daily, n = 48) at last valid rating.
      According to Clinical Global Impression (CGI) 68% in the remoxipride twice daily,
      58% in the three times daily and 60% in the haloperidol group were very much or
      much improved. Treatment-emergent extrapyramidal checklist symptoms (hypokinesia,
      rigidity and tremor) were statistically significantly more frequent and more
      severe during haloperidol than during remoxipride treatment despite a
      statistically significantly higher concurrent use of anticholinergic drugs in the
      haloperidol group. Haloperidol treated patients reported more tiredness and
      drowsiness than remoxipride treated patients. Also, haloperidol treated patients
      had a significantly higher frequency of extrapyramidal symptoms on 8 out of 10
      items of the Simpson and Angus scale.

PMID- 1978472
TI  - A double-blind comparative multicentre study of remoxipride and haloperidol in
      schizophrenia.
AB  - In a double-blind multicentre study of parallel group design the efficacy and
      safety of remoxipride and haloperidol were compared in a total of 96 patients
      with acute episodes of schizophrenic or schizophreniform disorder according to
      DSM-III. There were 48 patients in each treatment group; 27 men and 21 women in
      the remoxipride group, 33 men and 15 women in the haloperidol group. The median
      duration of illness was 7 years in both groups. The mean daily dose was 437 mg
      for remoxipride and 10.6 mg for haloperidol during the last week of treatment. No
      statistically significant differences in total BPRS scores were found between
      remoxipride and haloperidol. The median total BPRS scores at the start of active
      treatment were 26 in the remoxipride and 27 in the haloperidol group; these were
      reduced to 16 and 12.5, respectively, at the last rating. According to Clinical
      Global Impression (CGI), 43% of patients in the remoxipride group and 68% of
      those in the haloperidol group improved much or very much during treatment. This
      difference was not statistically significant. Treatment-emergent extrapyramidal
      side effects such as akathisia, tremor, and rigidity occurred significantly more
      frequently in the haloperidol group; this group also made more frequent use of
      anticholinergic drugs. Neither of the trial drugs seriously affected laboratory
      or cardiovascular variables. It is concluded that remoxipride has an
      antipsychotic effect in a dose range of 150-600 mg per day comparable to that of
      haloperidol in doses up to 20 mg per day but with fewer extrapyramidal side
      effects.

PMID- 1978473
TI  - A double-blind comparative study of remoxipride and thioridazine in the acute
      phase of schizophrenia.
AB  - Sixty-one patients with acute schizophrenia received either remoxipride (75-375
      mg daily) or thioridazine (150-750 mg daily) for 6 weeks. There was no
      statistically significant between-drug difference in improvement in mental state,
      as measured by the Brief Psychiatric Rating Scale, although the trend favoured
      thioridazine; global assessment of illness severity at the last rating also
      favoured thioridazine. Sedation, anticholinergic effects, autonomic dysfunction,
      and weight gain were significantly more common in patients receiving
      thioridazine. Both drugs produced few extrapyramidal effects, but both were
      associated with cardiovascular changes in two patients; neither drug produced
      significant abnormalities in laboratory tests.

PMID- 1978474
TI  - A double-blind comparative study of remoxipride and haloperidol in schizophrenic
      and schizophreniform disorders.
AB  - The antipsychotic effect of remoxipride was compared to that of haloperidol in a
      randomized double-blind study with parallel group design comprising 98 patients
      with schizophrenia or schizophreniform disorder according to DSM-III. After a 3-7
      day placebo washout period, patients received either 150-600 mg of remoxipride or
      5-20 mg of haloperidol daily for 6 weeks. No significant differences in efficacy
      were found between the two treatments. Treatment-emergent checklist symptoms such
      as hypokinesia, rigidity, and tremor occurred more frequently and were more
      severe during haloperidol than during remoxipride treatment despite a
      significantly higher concurrent use of anticholinergic drugs in the haloperidol
      group. Haloperidol-treated patients reported greater increases in sleep and
      salivation than remoxipride-treated patients. Shoulder shaking and tremor were
      reported as occurring more frequently in the haloperidol group according to the
      Simpson and Angus rating scale for extrapyramidal symptoms. In summary, the two
      drugs seemed to be equally efficacious, though the tolerability profile favoured
      remoxipride.

PMID- 1978475
TI  - A double-blind multicentre study comparing remoxipride, controlled release
      formulation, with haloperidol in schizophrenia.
AB  - A double-blind multicentre study was undertaken to compare the efficacy and
      safety of remoxipride in a controlled release (CR) formulation given once daily
      with haloperidol twice daily in patients with schizophrenic illness. In total,
      114 patients were included. All were diagnosed as schizophrenic or
      schizophreniform according to DSM-III. Their mean daily dose of remoxipride CR
      during the last week of treatment was 385 mg. In the haloperidol group the
      corresponding dose was 17 mg per day. The intended study period was 4 weeks with
      at least a one-day washout. No significant differences were found between
      treatments regarding efficacy variables. The median total Brief Psychiatric
      Rating Scale (BPRS) score was 40 in the remoxipride CR group at start of
      treatment and 21 at last valid rating. For the haloperidol group the
      corresponding figures were 40 and 22. Treatment-emergent extrapyramidal symptoms
      (Simpson and Angus rating) occurred statistically significantly more frequently
      and were more severe during haloperidol than during remoxipride CR treatment
      despite a statistically significantly higher concurrent use of anticholinergic
      drugs in the haloperidol group.

PMID- 1978476
TI  - Treatment programme and long-term outcome in chronic schizophrenia.
AB  - Antipsychotic drug treatment is usually started during an acute episode or
      exacerbation of a pre-existing psychosis. Although the medication has marked
      therapeutic benefit for most patients, ther is considerable heterogeneity in drug
      response. A variety of factors may influence this response, but at present we
      have no well-established predictors which would help targeting specific
      pharmacological treatments. The continuation of antipsychotic drug treatment to
      control persistent symptoms and to prevent further exacerbations or relapse has
      become a mainstay in the long-term treatment of schizophrenia. There are various
      considerations which come into play in deciding which patients should receive
      such treatment, at what dose, and for how long. Research in recent years has
      attempted to identify strategies to minimize the risks associated with long-term
      treatment (particularly tardive dyskinesia). In addition, other factors
      influencing long-term outcome have been better studied in combination with
      controlled drug treatment.

PMID- 1978477
TI  - Experiences of long-term treatment with remoxipride: efficacy and tolerability.
AB  - An international clinical trial programme was undertaken to evaluate the clinical
      safety and tolerability of remoxipride during a 12 month long-term study and to
      evaluate safety, tolerability and efficacy of remoxipride for up to 6 months in a
      double-blind comparison with haloperidol. A total of 145 patients were treated
      with remoxipride for at least 12 months. In the double-blind evaluation 106
      patients on remoxipride and 50 on haloperidol were included. The doses of
      remoxipride ranged between 90-600 mg daily and of haloperidol between 5-45 mg
      daily. The therapeutic efficacy of remoxipride obtained in short-term studies was
      maintained during long-term treatment in most patients and was similar to that of
      haloperidol. Remoxipride had a clear cut advantage concerning extrapyramidal
      symptoms and anticholinergic drugs were needed less frequently with remoxipride
      than with haloperidol. The tolerability and safety showed no clinically
      significant differences compared to the data from short-term studies. This
      indicates that remoxipride can be used safely and with maintained efficacy for
      long-term treatment.

PMID- 1978478
TI  - Safety evaluation in both short- and long-term treatment of schizophrenia with
      remoxipride.
AB  - Results for laboratory and cardiovascular variables in both short-term (4-6
      weeks) and long-term (greater than 6 weeks) double-blind studies in schizophrenic
      patients consistently showed comparably low incidences of both transient
      treatment-emergent changes and changes present at last rating for both
      remoxipride and haloperidol. The total incidence of serious adverse events in the
      short-term double-blind programme was approximately 2% for both remoxipride and
      haloperidol. The corresponding figure for remoxipride (n = 434) in long-term
      treatment was approximately 6%. Compared to those on haloperidol, fewer patients
      on remoxipride had trough plasma prolactin levels above the normal range in short
      term treatment. The results with long-term treatment with remoxipride were
      similar. Breast swelling and galactorrhoea were infrequent treatment-emergent
      side effects with either drug. It was impossible to evaluate menstrual
      disturbance in short-term studies but in long-term use the incidence of treatment
      emergent menstrual disorder was low in remoxipride patients. Too few patients
      continued treatment with haloperidol for a comparative long-term evaluation.
      Overall, based on the information available at present, remoxipride appears to
      offer a high degree of safety in both short-term and long-term treatment of
      schizophrenia.

PMID- 1978479
TI  - Antipsychotics in the elderly.
AB  - Neuroleptics are commonly prescribed medications in the geriatric population and
      have a broader spectrum of indications than in younger patients. In spite of the
      frequent use of neuroleptics in elderly patients with organic brain syndromes,
      there are relatively few studies that use double-blind, placebo-controlled
      methodology. The results of these studies are conflicting; however, there is
      sufficient evidence that symptoms of agitation, behaviourial dyscontrol, and
      psychosis are often responsive to neuroleptic treatment. Elderly patients with
      schizophrenia or other psychotic disorders may also benefit from neuroleptic
      treatment. As there is a potential for overuse of these medications among the
      elderly, clear definition of checklist symptoms is imperative. Furthermore,
      periodic reduction of dose and possible discontinuation of the drug should be
      considered since many of the checklist symptoms in this age group are
      environmentally related and time-limited. There has so far been little evidence
      to support the use of one neuroleptic over another. Side-effect profiles suggest
      that low doses of the high potency agents are safer and better tolerated in the
      elderly. Both therapeutic effects and side effects should be assessed at regular
      intervals.

PMID- 1978480
TI  - Pharmacokinetics of remoxipride in elderly psychotic patients.
AB  - The pharmacokinetics of remoxipride when given as single doses of 50 mg and
      repeated doses of 50 mg, 100 mg, and 200 mg twice daily to 10 elderly psychotic
      patients (71-89 years) were compared with the findings of two other studies to
      reveal any age-related differences. The three studies comprised a total of 38
      patients in three distinct age groups: elderly (71-89 years), middle-aged (46-69
      years) and young (19-36 years). AUC, Cmax and Cmin of both total and unbound
      remoxipride increased with increasing age. The unbound fraction was similar in
      the three age groups. The half-life was prolonged in the elderly, most probably
      caused by a decrease in intrinsic clearance. A two-fold increase in AUC of both
      total and unbound concentrations was observed in the elderly group compared to
      the young, suggesting that patients over 70 years in general require half the
      dose needed by young adult patients. In general, the pharmacokinetics of
      remoxipride in the elderly are linear.

PMID- 1978481
TI  - Remoxipride versus thioridazine in elderly psychotic patients.
AB  - A total of 18 hospitalized elderly psychotic patients in need of antipsychotic
      treatment took part in a double-blind exploratory study concerning the safety,
      tolerability and efficacy of remoxipride and thioridazine. Their median age was
      78 years (range 66-90 years). Over the study period of 6 weeks, 9 patients
      received remoxipride and 9 thioridazine. Both drugs were given in a dosage range
      of 50-200 mg/day. The median total score on the Brief Psychiatric Rating Scale at
      the start of active treatment was 18 in the remoxipride group and 24 in the
      thioridazine group. The scores were reduced to 6 and 7, respectively, at the last
      rating. The Clinical Global Impression at last rating showed 4 of the 9
      remoxipride patients to be very much improved compared to 1 of the 9 thioridazine
      patients. Apart from three reports of severe drowsiness in the thioridazine
      group, the incidence of treatment-emergent adverse effects was low in both
      groups. No clinically significant aberrations were seen in laboratory tests or
      cardiovascular data. In conclusion, remoxipride seemed to be well tolerated in
      this group of patients and its antipsychotic efficacy in the doses used is
      promising.

PMID- 1978482
TI  - Atypical neuroleptics: role of multiple receptors, endogenous dopamine, and
      receptor linkage.
AB  - A variety of biological factors may account for the atypical lack of parkinsonism
      that is a characteristic of the administration of the many 'atypical'
      neuroleptics. Although dopamine D2 receptor blockade continues to be a dominant
      feature of successful neuroleptics, the concomitant blockade of muscarinic or
      serotonergic S2 receptors helps to prevent neuroleptic-induced parkinsonism for
      some atypical neuroleptics (clozapine, thioridazine, risperidone). The D2
      selective benzamides, however, do not block other known receptors (with the
      possible exception of sigma sites). Therefore, the atypical nature of the
      benzamides may be based on their sensitivity to the level of endogenous dopamine
      released in the different regions of the brain. Finally, atypical neuroleptic
      action may possibly stem from direct linkage between different receptors coupled
      through components of the G protein system.

PMID- 1978483
TI  - Neuropharmacological and behavioural properties of remoxipride in the rat.
AB  - Remoxipride blocks dopamine agonist-induced effects in the rat, mediated by
      dopamine D2 receptors with an in-vivo potency less than that of haloperidol but
      greater than that of chlorpromazine, thioridazine, and sulpiride. Unlike
      haloperidol and sulpiride, remoxipride has weaker antagonistic effects towards
      presynaptic dopamine activity compared to its effects on postsynaptically
      mediated activity. Remoxipride causes a preferential inhibition of dopamine
      agonist-induced locomotion as compared to stereotyped behaviour, suggesting that
      it may exert a preferential blockade of mesolimbic dopamine neurotransmission.
      The low tendency of remoxipride to cause catalepsy in the rat is indicative of a
      weak effect on striatal dopamine neurotransmission and predicts a low liability
      to induce extrapyramidal side effects in man. Remoxipride causes a smaller
      elevation of prolactin than sulpiride at doses producing central dopamine
      receptor blockade. The results suggest that remoxipride, unlike haloperidol, can
      discriminate between different types of dopamine mediated functions probably by
      having a preferential action on subpopulations of functionally coupled dopamine
      D2 receptors.

PMID- 1978485
TI  - Pharmacokinetics of antipsychotic drugs in man.
AB  - Variability in the outcome of treatment with antipsychotic drugs may be due to
      differences in compliance and to variations in pharmacokinetics and concentration
      response relationships at the receptor level. Among the various chemical classes
      of neuroleptics, the butyrophenones, the phenothiazines, and the thioxanthenes
      have similar pharmacokinetics, and show larger inter-individual variations in
      plasma drug levels after oral than after intramuscular doses. Compared to the
      "classical" neuroleptics, the more water-soluble benzamide derivatives have
      significantly shorter elimination half-lives, and show smaller inter-patient
      variations in plasma level: dose ratios at steady state.

PMID- 1978484
TI  - Biochemical pharmacology of the atypical neuroleptic remoxipride.
AB  - In vitro receptor ligand binding studies in the rat showed that remoxipride
      displaced different radioligands at the dopamine D2, but not the D1 receptor.
      Remoxipride did not block dopamine-stimulated adenylate cyclase activity in vitro
      suggesting that it did not directly interact with the dopamine D1 receptor. Like
      other antipsychotic compounds, it increased dopamine turnover in the dopamine
      rich areas of the brain. It showed no affinity for a wide range of
      neurotransmitter receptors, with the exception of the opiate sigma receptor. The
      affinity of remoxipride for the D2 receptor was low in vitro, while in vivo, the
      affinity was relatively high. Remoxipride was far more potent in preventing
      [3H]raclopride-binding than [3H]spiperone-binding to the D2 receptor in vivo.
      When the D2 receptor was labelled with [3H]spiperone, remoxipride was shown to
      exert a preferential blockade of this binding in extrastriatal areas of the brain
      (for example, olfactory tubercle, septum, substantia nigra) in vivo. After the
      injection of high doses of remoxipride most if not all drug in the brain was
      identified as authentic remoxipride. After injection of [3H]remoxipride in
      smaller and larger doses, radioactivity was detected in all areas of brain
      examined, including cerebellum and neocortex. Most of the remoxipride-derived
      radioactivity was found in the choroid plexus and circumventricular organs, while
      smaller amounts were recovered in the striatum, olfactory tubercle, and
      substantia nigra. Taken together, these findings suggest that remoxipride acts at
      both the central D2 and sigma receptors and that its affinity for the D2 receptor
      is relatively low in vitro. A regional preference for D2 receptors can be
      observed in vivo depending upon the radioligand used.

PMID- 1978486
TI  - Clinical pharmacokinetics of remoxipride.
AB  - The clinical pharmacokinetics of remoxipride, a pure enantiomer, have been
      studied in healthy volunteers and patients. After oral administration the drug is
      rapidly and almost completely absorbed with a bioavailability above 90%. Thus
      remoxipride is a low clearance drug, with a systemic plasma clearance of about
      120 ml/min, and without any first-pass metabolism. The apparent volume of
      distribution is 0.7 1/kg, about 80% being bound to plasma proteins (mainly alpha
      1-acid glycoprotein). Remoxipride has a plasma half-life in the range of 4-7 h
      and is eliminated by both hepatic metabolism and renal excretion. Slightly more
      than 70% of the dose is recovered as urinary metabolites and about 25% is
      excreted unchanged. Steady-state plasma levels are reached within 2 days, and
      they increase linearly with doses up to 600 mg daily. There is no evidence that
      active metabolites of remoxipride are present in the blood. Decreased renal
      function is associated with increased levels of remoxipride, whereas moderate
      cirrhosis of the liver only slightly affects elimination. There are no
      pharmacokinetic interactions between remoxipride and diazepam, ethanol,
      biperiden, or warfarin.

PMID- 1978487
TI  - Pharmacokinetics of an oral controlled release formulation of remoxipride: a
      double-blind, crossover comparison with conventional formulation in chronic
      schizophrenics.
AB  - Twenty-four stable, chronic schizophrenic inpatients were entered in a double
      blind, crossover study designed to compare single-dose and steady-state
      pharmacokinetics of remoxipride immediate release (IR) 200 mg twice daily and
      controlled release (CR) 400 mg once daily. The CR formulation showed a
      significantly delayed absorption of remoxipride from the gastrointestinal tract.
      At steady state there was significantly less fluctuation in plasma
      concentrations. The other pharmacokinetic variables studied showed no difference.
      The mean relative bioavailability with regard to the amount of remoxipride
      absorbed after administration in CR form as compared with the IR form was 97%.
      Both formulations were well tolerated and there was no difference in either the
      incidence or the severity of adverse events. It was concluded that, from a
      pharmacokinetic point of view, the CR formulation of remoxipride was suitable for
      a once daily dosage schedule.

PMID- 1978488
TI  - Plasma concentration of remoxipride in relation to antipsychotic effect and
      adverse symptoms. The Canadian Remoxipride Study Group.
AB  - The possible relationship between plasma concentration of remoxipride and
      antipsychotic effect/adverse symptoms has been evaluated in a 6-week double-blind
      dose-finding study in schizophrenic patients. The study comprised 3 parallel
      groups with fixed daily doses of 30-90 mg, 120-240 mg or 300-600 mg, divided in
      order to be given three times a day. A total of 79 patients from the three
      groups, who were treated with the maximum dose for 4 weeks or more, were included
      in the analysis. All patients had reached steady-state at week 2 and the intra
      individual trough remoxipride plasma levels remained stable over the study
      period. The mean steady-state trough concentrations were found to be linearly
      related to the dose. Responders to remoxipride treatment were observed over the
      total concentration range of 0.24-13.50 mumols/l. Reductions of dose or
      discontinuations of treatment due to adverse symptoms were not associated with
      elevated remoxipride concentrations. In conclusion, no obvious relationship
      between plasma concentration of remoxipride and its antipsychotic effect or
      adverse symptoms was established.

PMID- 1978489
TI  - Tolerability and pharmacokinetics of remoxipride after intramuscular
      administration.
AB  - A study was undertaken in seven schizophrenic patients to evaluate the
      tolerability and examine the pharmacokinetics of intramuscularly administered
      remoxipride after a single 200 mg dose and at steady state following repeated
      doses of 200 mg twice daily for one week. Comparisons of AUC, t1/2 and tmax using
      the Wilcoxon's signed rank test showed no significant difference between single
      dose and steady state indicating that the pharmacokinetics of intramuscular
      remoxipride were linear. The steady-state Cmax was found to be significantly
      larger than that after single dose and the increase was accounted for by the
      predicted accumulation factor, assuming linear kinetics. Although the inter
      individual variability in plasma concentrations was large, the intra-individual
      variability was low as shown by the reproducibility of the single-dose and steady
      state plasma curves. Remoxipride, administered intramuscularly, was well
      tolerated.

PMID- 1978490
TI  - Effects of remoxipride on psychomotor performance, alone and in combination with
      ethanol and diazepam.
AB  - The effects of remoxipride, alone and in combination with ethanol and diazepam,
      on sensory, cognitive, and neuromotor performance were studied in 12 healthy
      volunteers (7 men, 5 women). The study was of double-blind randomized, crossover
      design with each subject receiving six different single-dose experimental
      treatments at six sessions. Tests of sensory, cognitive, and neuromotor functions
      were carried out, together with subjective assessments. Remoxipride alone seemed
      to have no effect on the sensory functions measured, but it affected cognitive
      and neuromotor functions to a limited extent. In general the effects of ethanol
      and diazepam alone were more pronounced than those of remoxipride. When
      remoxipride was combined with either ethanol or diazepam, there was a tendency
      for the effect to be additive.

PMID- 1978491
TI  - Cognitive disturbances in neuroleptic therapy.
AB  - Eighteen patients (7 men, 11 women) from one of the centres taking part in a
      multicentre comparative study of remoxipride and haloperidol in the treatment of
      acute schizophrenia were investigated separately to study the effect of the two
      neuroleptic drugs on cognitive abilities. The tests of cognitive ability that
      were used are standard in West Germany. The results of this study indicate that
      there could be differences between remoxipride and haloperidol regarding their
      effects on cognitive abilities--the patients who had been treated for four weeks
      with remoxipride showed a greater "mental fitness".

PMID- 1978493
TI  - Guidelines for the dosage of antipsychotic drugs.
AB  - When commonly recommended guidelines for the dosage of neuroleptic drugs are
      critically reviewed, unanswered questions outnumber accepted rules. The
      relationship between dose and therapeutic efficacy remains far from clear, and
      despite lack of data there has been a trend in recent years to escalate dosage.
      Average clinical antipsychotic potency correlates closely with the affinity of
      the drug for dopamine (D2) receptors. Correlations of blood levels of
      neuroleptics with clinical efficacy are inconsistent. Assessments of immediate
      and follow-up treatment indicate that moderate doses are adequate for most
      psychotic patients and fail to support the use of high doses (more than the
      approximate equivalent of 300-600 mg chlorpromazine daily). Occasionally however,
      patients, perhaps because of idiosyncratic pharmacokinetics, require higher doses
      and do not conform to the statistical data for outcome. More precise results for
      determining the optimum dose of antipsychotic compounds in schizophrenics in the
      future, may be available from positron emission tomographic (PET) techniques.

PMID- 1978492
TI  - Drug interaction studies with remoxipride.
AB  - The interaction potential of remoxipride was investigated with biperiden,
      warfarin, diazepam, and ethanol. The studies were conducted in 12 healthy
      volunteers each of whom received single doses of remoxipride, the interacting
      drug, and the combination in a randomized crossover design. Remoxipride and
      biperidene had no influence on each other's pharmacokinetics. The
      pharmacokinetics of warfarin enantiomers were uninfluenced by remoxipride.
      Ethanol and diazepam had no effect on the pharmacokinetics of remoxipride. The
      effect of remoxipride on the elevation of plasma prolactin levels was not
      modified by biperiden and the effect of warfarin on the prolongation of
      prothrombin time was uninfluened by remoxipride. Remoxipride showed no
      pharmacokinetic interaction with any of the drugs studied, nor was any
      pharmacodynamic interaction observed in the remoxipride versus biperiden and
      remoxipride versus warfarin studies.

PMID- 1978494
TI  - Distribution of remoxipride to the human brain and central D2-dopamine receptor
      binding examined in vivo by PET.
AB  - Remoxipride is a new antipsychotic drug that binds selectively to the D2-dopamine
      receptor subtype as demonstrated in animal studies in vitro and in vivo. It is
      generally assumed that the antipsychotic effect of neuroleptic drugs is mediated
      by blockade of dopamine receptors. The aim of the present study was to use
      positron emission tomography (PET) and the ligand [11C] raclopride to examine the
      central D2-dopamine receptor occupancy in man during oral administration of
      remoxipride. After oral administration of remoxipride 100 mg three times daily to
      a healthy male subject there was a 73% central D2-dopamine receptor occupancy. In
      a schizophrenic patient treated with remoxipride 200 mg twice daily there was a
      71% occupancy. These occupancy values are similar to the values of 65-85%
      previously found in a series of patients treated with neuroleptics representative
      of all currently used chemical classes. In a separate experiment, remoxipride was
      labelled with 11C and injected intravenously and the distribution of
      radioactivity to the brain examined. Radioactivity appeared in the brain during
      the first minutes after injection and 4.5 min after injection it accounted for
      0.8% of the total radioactivity injected, thus indicating that [11C]remoxipride
      had rapidly passed through the blood-brain barrier.

PMID- 1978495
TI  - Monoamines and schizophrenia.
AB  - The hypothesis that central biogenic amines may play a role in the
      pathophysiology of schizophrenia was originally based upon the fact that
      hallucinogenic and antipsychotic drugs have profound effects on central
      transmitter pathways where dopamine, noradrenaline and serotonin are involved.
      The structural similarities between hallucinogenic drugs such as amphetamine and
      mescaline, and catecholamines on the one hand and lysergic acid diethylamide
      (LSD) and indolamines such as serotonin on the other hand have by direct
      experimentation been shown to explain their important effects on the transmitter
      systems. The marked effect of several classes of chemically different
      antipsychotic drugs on central dopamine receptor function formed the basis for
      the dopamine hypothesis regarding the mechanisms of action of these drugs and
      also for the hypothesis that dopamine D2 receptor function played a significant
      role in the pathophysiology of schizophrenia. Direct experimental analysis of
      aminergic functions in the brain of schizophrenic patients, both during life and
      post mortem, has been and will for the foreseeable future continue to be a
      rational approach to the further elucidation of the validity of these hypotheses.
      Analysis of metabolite levels in the cerebrospinal fluid and plasma of
      schizophrenic patients has shown great variation in the results with reports of
      both elevated and reduced release of amines in the brains of schizophrenic
      patients. Analysis of the aminergic receptor structures in the postmortem human
      brain has relatively consistently revealed an increased density of D2 receptors
      in the major basal ganglia of schizophrenic patients. Whether these alterations
      represent a primary feature of brain structure in schizophrenia or a drug-induced
      effect still remains to be shown. Positron emission tomographic (PET) scan
      studies of D2 receptors in schizophrenia have demonstrated both increased
      densities and absence of change in the characteristics of D2 receptors in the
      patients as compared to matched controls.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1978496
TI  - A controlled dose-ranging study of remoxipride and haloperidol in schizophrenia-
      a Canadian multicentre trial.
AB  - The efficacy and side-effect profile for three dose ranges of remoxipride were
      compared with haloperidol in 242 schizophrenic inpatients in 13 centres. All
      patients were in a productive phase of schizophrenia according to DSM-III
      criteria. Relative efficacy of low dose (30-90 mg daily) vs middle dose (120-240
      mg daily) vs high dose (300-600 mg daily) was compared with the standard dose of
      haloperidol (15-45 mg daily), as were the side effects. It was concluded that the
      therapeutic efficacy of remoxipride was comparable to that of haloperidol for
      acute episodes of schizophrenia; that the low dose range was significantly less
      effective than the higher ranges; that there was a clear advantage of remoxipride
      over haloperidol with respect to incidence and severity of extrapyramidal
      symptoms. The general safety profile of remoxipride as assessed from clinical
      chemistry, haematology, and cardiovascular variables suggests that remoxipride in
      the dose ranges studied can be used safely for the treatment of schizophrenic
      patients.

PMID- 1978497
TI  - A double-blind multicentre comparison of remoxipride, at two dose levels, and
      haloperidol.
AB  - A total of 186 patients who met the DSM-III criteria for schizophrenia were
      admitted to a double-blind randomized multicentre trial in which the efficacy and
      safety of remoxipride at two dose levels was compared with those of haloperidol.
      Over a period of six weeks the patients received remoxipride 100-300 mg/day (n =
      60), remoxipride 200-600 mg/day (n = 61), or haloperidol 10-30 mg/day (n = 64).
      There was no significant difference between the three treated groups with regard
      to the Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression (CGI)
      scores obtained. Remoxipride, at both dosage ranges used, thus had comparable
      therapeutic efficacy to that of haloperidol. In contrast, extrapyramidal symptoms
      occurred significantly more frequently in the group treated with haloperidol.
      Laboratory tests and cardiovascular investigations showed no specific drug effect
      in any of the treated patients. Remoxipride is thus effective in acute treatment
      of schizophrenia at both dosage levels and has an advantage over haloperidol in
      neurological acceptability.

PMID- 1978498
TI  - The neuroleptics: a historical survey.
AB  - The history of the neuroleptic drugs has been marked by various milestones: some
      have been successes, others have been associated with complications and side
      effects, especially when the drugs have been misused. At the Paris meeting in
      1955, it was confirmed that neuroleptics were indicated in chronic psychoses. In
      1963, a new form of long-acting neuroleptic was introduced which appeared useful
      for non-compliant patients. However, following the introduction of the American
      concept of "CPZ- equivalent" which is opposed to the European distinction between
      sedative and "disinhibitory" neuroleptics, the problem of the development of
      tardive dyskinesia became serious. The antipsychotic actions of the neuroleptics
      in some psychoses eventually led to the so-called "dopaminergic theories" of
      schizophrenia, which are still under discussion. It should be underlined that the
      specific antimanic action of neuroleptics, which is included in the early
      definition, has been prematurely neglected. In fact, mania is the opposite of
      depression and, in general, the antidepressants are "anti-neuroleptic". The
      neurobiological studies of the neuroleptics resulted in the differentiation of
      the compounds according to their action on different parts of the dopamine
      system, especially on the mesolimbic and mesocortical structures. This was
      particularly useful in the efforts to avoid extrapyramidal side effects. The
      clarification of the role of the D1 and D2 dopamine receptors has been important
      in understanding the development of tardive dyskinesias. There are now some 50
      different neuroleptic drugs, in about a dozen chemical families, which can be
      classified by an "automatic" statistical method.

PMID- 1978499
TI  - Clinically relevant differences between antipsychotic compounds.
AB  - All currently available antipsychotic drugs in general clinical use for the
      treatment of schizophrenia have in common the pharmacological property of
      dopamine receptor blockade and it is upon this that their anti-psychotic effects
      are thought to depend. Where they differ is in the spectrum of side effects they
      may produce, in their clinical profile, in potency, and in time course. Such
      differences reflect variations in pharmacological properties, both
      pharmacodynamic and pharmacokinetic. The substituted benzamides (sulpiride,
      remoxipride) are highly selective D2 receptor blockers and this pharmacological
      specificity confers important clinical advantages. In practice the choice of
      which antipsychotic drug to use in any given clinical situation depends on the
      degree of psychopathology present, the purpose for which treatment is being
      given, and the patient's age and general physical health.

PMID- 1978500
TI  - Clinical profile of remoxipride--a combined analysis of a comparative double
      blind multicentre trial programme.
AB  - Nine double-blind studies comparing remoxipride to haloperidol in the treatment
      of acute schizophrenia formed the basis of this analysis. All studies followed a
      basic protocol with the main assessments performed regularly during the 4-6 week
      trial period according to the same methodology, thus allowing the data to be
      pooled. The results showed that remoxipride in a daily dose of 150-600 mg had a
      therapeutic effect comparable to that of haloperidol (5-45 mg/day), both on
      positive and negative symptoms. There was a clear advantage for remoxipride over
      haloperidol with regard to adverse events/symptoms, particularly extrapyramidal
      symptoms, but also drowsiness/somnolence and tiredness/fatigue. Anticholinergic
      drugs were used consistently less frequently as concomitant medication to
      alleviate extrapyramidal symptoms in the remoxipride group: the use of
      sedatives/hypnotics was approximately the same in both groups. Based on these and
      supportive clinical data, remoxipride seems to have a clinical profile
      characterized by antipsychotic efficacy in acute schizophrenia, apparently equal
      to that of haloperidol, and good tolerability in being non-sedative (in terms of
      drowsiness/somnolence) and with low incidences of extrapyramidal, autonomic, and
      endocrine symptoms.

PMID- 1978501
TI  - Remoxipride and haloperidol in schizophrenia: a double-blind multicentre study.
AB  - Ninety-two patients with schizophrenia were included in a double-blind
      multicentre parallel-group trial comparing remoxipride and haloperidol. The mean
      daily dose during the last week of treatment was 316 mg (range, 150-600 mg) in
      the remoxipride group and 8.7 mg (range, 5-20 mg) in the haloperidol group. The
      study period was six weeks with at least one day of washout. Both Clinical Global
      Impression (CGI) rating, and Brief Psychiatric Rating Scale (BPRS) total scores
      declined at the end of the trial compared with pretreatment values in both
      groups. No significant differences were found between the remoxipride and
      haloperidol groups with regard to the treatment outcome. Treatment-emergent
      extrapyramidal symptoms were statistically more frequent and more severe during
      haloperidol than during remoxipride treatment. Haloperidol-treated patients
      reported also significantly more concentration difficulties. Severe
      extrapyramidal side effects in the haloperidol group and clinical ineffectiveness
      in the remoxipride group were the most frequent reasons for premature
      discontinuation of treatment.

PMID- 1978502
TI  - Clinical study of syncope during acupuncture treatment.
AB  - From August 1988 to April 1989, we observed 52 patients who developed so-called
      'needle fainting' (or what the Chinese call 'Yun-Cheng' phenomenon) 55 times
      among a total sample of 28,285 procedures of acupuncture therapy at the Center
      for Traditional Medicine of Veterans General Hospital in Taipei. Of these
      syncopal patients, 35 were male and 17 were female. Their mean age was 45 years
      (with a range of 11 to 72 years). All patients were in an upright position when
      needle fainting occurred. Their usual manifestations were pallor, cold sweating,
      nausea, and bradycardia. They all recovered soon after lying down; no one
      developed a complete loss of consciousness. No mortality was noted. When
      comparing the patients who experienced syncope during their first visit to our
      Clinic (Group I, n = 27) with the patients who experienced syncope in a follow-up
      treatment (Group II, n = 25; 3 patients had 2 episodes in sequential treatments),
      we found a significantly higher incidence of needle fainting (p less than 0.0001)
      in Group I patients (27 out of 2,855 or 0.94%) than in Group II patients (28 out
      of 25,430 or 0.11%). The mean age of Group I patients (39 +/- 15.4 years) was
      significantly less than that of Group II patients (51.6 +/- 18.0 years) (p less
      than 0.001). The coexistence of other medical problems was significantly higher
      in Group II patients (72%) than in Group I patients (18.5%) (p less than 0.0001).

PMID- 1978503
TI  - Studies on the enhanced effect of acupuncture analgesia and acupuncture
      anesthesia by D-phenylalanine (2nd report)--schedule of administration and
      clinical effects in low back pain and tooth extraction.
AB  - D-phenylalanine (DPA) is known to block the activity of carboxypeptidase, an
      enzyme which degrades enkephalins, endogenous morphine-like substances.
      Therefore, it is considered that DPA administered as an inhibiting drug of this
      degrading enzyme might prolong analgesia induced by acupuncture. 1) Thirty
      patients suffering from chronic low back pain were treated with acupuncture 30
      minutes after the oral administration of 4.0 grams of DPA. The results were:
      excellent in 7 cases, good in 11, fair in 6 and poor in 6. Cases graded excellent
      and good were then compared with a placebo group. The effect was increased 26% in
      the DPA-acupuncture group, which shows no statistically significant difference (P
      less than 0.1). 2) In 56 patients, tooth extraction was performed under
      acupuncture anesthesia: 18 had received 4.0 gram of DPA (P.O.) 30 minutes
      earlier. The results were excellent in 8, good in 6, fair in 3, and poor in 1.
      The excellent and good cases were compared with 38 placebo group cases. The
      effect in the DPA-acupuncture anesthesia group was significantly increased by 35%
      (P less than 0.01). 3) In order to determine the optimum time for the
      administration of DPA, two schedules of administration were compared. [1] DPA was
      given on the previous day in three 0.5 gram doses (26 cases). [2] A single 4 gram
      dose was administered 30 minutes before treatment (30 cases). The results from
      the "excellent", "good" and "fair" cases showed a 16% increase in effectiveness
      when DPA was administered the day before, not a statistically significant
      difference (P less than 0.1), but a clear tendency to increase was observed. The
      above findings show that DPA has an enhancing effect on acupuncture analgesia and
      anesthesia in clinical practice.

PMID- 1978504
TI  - Storing of qi gong energy in various materials and drugs (qi gongnization): its
      clinical application for treatment of pain, circulatory disturbance, bacterial or
      viral infections, heavy metal deposits, and related intractable medical problems
      by selectively enhancing circulation and drug uptake.
AB  - In the process of evaluating the effects of external Qi Gong on inanimate
      substances by the Bi-Digital O-Ring Test, Qi Gong energy was shown to have a
      polarity which the author designated for convenience sake (+) or (-), where (+)
      increases the strength of muscles and (-) weakens them. Depending upon how
      external Qi Gong is applied and from which part of the body it emanates, the
      polarity changes. In general, it was found that, when (+) polarity is applied to
      the painful area or spastic muscles or arteries in vaso-constriction it often
      reduced or eliminated the pain, spastic muscles or circulatory disturbances. The
      author succeeded in storing part of the Qi Gong energy in inanimate materials,
      such as papers, metals (such as a sheet of aluminum foil), glass, stone, band
      aids, clothes, drugs, etc. in bi-polar (one end of the same material becomes (+)
      polarity and the other end of the same material becomes (-) polarity) form in one
      material or uni-polar, i.e., the entire material either has pure (+) polarity or
      (-) polarity. Water, EPA, vitamins, antibiotics and other drugs were also
      converted to (+) polarity. When the material has a bi-polar state, it becomes
      possible to eliminate one of the polarities by applying certain changing
      electrical fields. The effect of placing (+) polarity Qi Gong energy stored
      material was compared with direct application of the Qi Gong on pain, spastic
      muscle and spastic vertebral arteries. The therapeutic effects of these 2 methods
      were quite similar for the identical time duration but a more predictable effect
      was often obtained in the former. As our previous study indicates that
      acupuncture, electrical stimulation (1-3 pulses/sec.), as well as Qi Gong not
      only improved the microcirculatory disturbance and relaxed spastic muscles and
      vaso-constrictive arteries but also reduced or eliminated the pain and also
      selectively enhanced drug uptake to the area where drugs could not be delivered
      due to existing circulatory disturbances, by placing (+) Qi Gong stored material,
      such as a sheet of paper or aluminum foil, band-aid or clothes. Bi- Digital O
      Ring Test evaluation indicated that not only did it produce all the beneficial
      effects of Qi Gong but also enhanced the drug uptake selectively in the area
      where it is necessary for the drug to be delivered for effective treatment, and
      reduced lead deposits in tissue.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1978505
TI  - The effects of massage in patients with chronic tension headache.
AB  - 21 female patients suffering from chronic tension headache received 10 sessions
      of upper body massage consisting of deep tissue techniques in addition to softer
      techniques in the beginning. When found, trigger points were carefully and
      forcefully massaged. The range of cervical movements, surface ENMG on mm.
      frontalis and trapezius, visual analogue scale (VAS) and Finnish Pain
      Questionnaire (FPQ), and the incidence of neck pain during a two week period
      before and after the treatment, and at 3 and 6 months during the follow-up period
      together with Beck depression inventory were taken for evaluation and follow-up.
      The range of movement in all directions increased, and FPQ, VAS and the number of
      days with neck pain decreased significantly. There was a significant change in
      ENMG on the frontalis muscle whereas changes in trapezius remained insignificant.
      Beck inventory showed an improvement after the treatment. This study confirmed
      clinical and physiological effects of massage.

PMID- 1978506
TI  - Measurements of human bioluminescence.
AB  - In measuring the output of light from the human skin, we estimated the total
      photon rates to be of the order of 170-600 photons/s/cm2, depending on anatomical
      location. The light was strongest at the red end of the spectrum, but fell below
      detectable levels in the ultraviolet. Significant variations were observed
      between individuals in both photon rate and spectral profile. The photon rate
      also varied significantly with time for a single individual. The possible source
      of this light and its significance are discussed.

PMID- 1978507
TI  - The effect of benzodiazepines administration on auricular symptomatological
      evidence.
AB  - The aim of this study is to verify the response of auricular skin to
      interoceptive stimuli in two groups of patients suffering from a gastroenteral
      pathology. Patients were submitted to a complete examination of auricle, in order
      to detect morphological alterations and painful points, and to a diagnostic
      digestive endoscopy. A group of patients took benzodiazepines at the moment of
      auricular examination; the second group did not take any drug. Results show that
      there is a significantly lower number of auricular painful points in the patients
      taking benzodiazepines in comparison with the patients who did not take such
      drug. In the patients treated with benzodiazepines the auricular diagnosis of
      painful points does not seem to be reliable.

PMID- 1978508
TI  - Peripheral neurohumoral factors and central control of homeostasis during altered
      sodium intake.

PMID- 1978509
TI  - New developments in the pathology of Parkinson's disease.
AB  - Recent data on neuronal cytoskeletal pathology of Lewy bodies, a major anatomical
      hallmark of PD, suggest pathological phosphorylation of neurofilament proteins
      with ubiquitination, but their relation to neuromelanin and cell degeneration is
      unknown. Quantitative morphological studies in PD indicate that in addition to
      nigrostriatal dopaminergic pathways, other dopaminergic, noradrenergic,
      serotonergic, and cholinergic systems are involved, causing multiple
      neuromediator dysfunctions. Dementia in PD is not only related to cortical AD
      pathology, but also to a variety of central nervous system lesions.

PMID- 1978510
TI  - Parkinson's disease: anatomy, pathology and therapy. Ninth International
      Symposium on Parkinson's Disease. Jerusalem, Israel, June 5-9, 1988. Proceedings.

PMID- 1978512
TI  - The dopaminergic nigropallidal projection in primates: distinct cellular origin
      and relative sparing in MPTP-treated monkeys.
AB  - In summary, our findings revealed the existence in primates of a dopaminergic
      pallidal projection that arises from neurons of the substantia nigra-ventral
      tegmental area complex and terminates preferentially in the internal pallidum.
      This projection is largely distinct from the nigrostriatal dopaminergic pathway
      and appears to be relatively spared in parkinsonian monkeys. Thus, in addition to
      their potent influence at striatal levels, the midbrain dopaminergic neurons may
      directly modulate the activity of basal ganglia output neurons at pallidal
      levels.

PMID- 1978511
TI  - The antiparkinsonian activity of dopamine agonists and their interaction with
      central dopamine receptor subtypes.

PMID- 1978513
TI  - The role of iron in the basal ganglion.

PMID- 1978515
TI  - Changes of tyrosine hydroxylase in parkinsonian brains and in the brains of MPTP
      treated mice.

PMID- 1978514
TI  - The nigrostriatal system in Parkinson's disease.
AB  - Patterns of dopaminergic cell loss in the midbrain and patterns of mesostriatal
      fiber loss in the caudate nucleus and putamen are described for cases of
      idiopathic Parkinson's disease. Neither cell loss nor fiber loss is homogeneous.
      In the midbrain, quantitative analysis points to a selective vulnerability of
      neurons in the most heavily pigmented dopaminergic cell groups. In the striatum,
      a dorsolateral-to-ventromedial gradient of loss appears to characterize both the
      caudate nucleus and the putamen. These patterns of loss and sparing have
      implications both for analysis of the clinical symptoms of Parkinson's disease
      and for study of the etiology of this disease.

PMID- 1978516
TI  - Intracerebroventricular infusion of (+)-4-propyl-9-hydroxy-naphthoxacine in
      monkeys with MPTP-induced akinesia.

PMID- 1978517
TI  - Chronic administration of MPTP to marmosets.

PMID- 1978518
TI  - Distinctive aspects of cognitive dysfunction in Parkinson's disease.

PMID- 1978519
TI  - Ultrastructure and immunocytochemistry of left and right nigrostriatal system
      after lesion of right side of substantia nigra of rat.

PMID- 1978520
TI  - Early dopamine agonist treatment in Parkinson's disease.

PMID- 1978521
TI  - Mesulergine: a dopamine agonist with novel properties in Parkinson's disease.

PMID- 1978523
TI  - [Changes in intraocular pressure and aqueous humor dynamics of normal human eyes
      after topical application of bunazosin hydrochloride].
AB  - The effects of topically applied bunazosin hydrochloride, a recently developed
      highly selective alpha 1-adrenergic antagonist, on intraocular pressure,
      pupillary diameter, aqueous protein concentration, anterior chamber volume,
      aqueous flow rate and tonographic outflow facility were investigated in eight
      normal human volunteers. A single application of 0.1% bunazosin hydrochloride
      caused a significant unilateral reduction in the intraocular pressure from 30
      minutes through 4 hours after the application, with a maximum decrease of 2.0 +/-
      0.5mmHg (mean +/- SEM) below the contralateral control eyes at 2 hours post
      application. Neither pupillary diameter, anterior chamber volume nor outflow
      facility was affected by the drug application. Both aqueous protein concentration
      measured with a flare-cell meter and aqueous flow rate determined by
      fluorophotometry were unaltered. The mechanism of intraocular pressure reduction
      appears to be an increase in uveoscleral outflow and/or a decrease in episcleral
      venous pressure.

PMID- 1978522
TI  - The efficacy of levodopa treatment declines in the course of Parkinson's disease:
      do nondopaminergic lesions play a role?

PMID- 1978525
TI  - Structure, molecular biology and immunology of the cuticle of parasitic
      nematodes.

PMID- 1978524
TI  - The nematode cuticle is a highly complex structure.

PMID- 1978526
TI  - Comparison of the cuticular structure of parasitic nematodes recognized by
      immunocytochemical and lectin binding studies.
AB  - The cuticle structure of some nematode species was studied by immunogold and
      lectin-gold techniques. The gold labelling made it possible to distinguish the
      cuticle layers by the distribution and/or the density of the marker. On the other
      hand, no labelling pattern was found which led to a clear grouping of the layers
      into larger 'zones', since there were no subunits consisting of more than one
      layer which reacted in a characteristic way as compared to the rest of the
      cuticle. The outer surface of the epicuticle of parasitic adult worms turned out
      to be highly inert; it did not react with any of the antibodies or lectins
      tested. The cuticle of parasitic nematodes seems to function as a protection
      against the host's defense mechanisms rather than as an interaction site. An
      immunogenic component on the surface was only found in infective larvae. All
      antibodies and lectins showed a preferential binding to the electron dense layers
      and fibrous structures (HPL/GalNAc, WGA/GlcNAc) or to the amorphous ground
      substance (Con A/Glc, RCA I/Gal).

PMID- 1978527
TI  - Molecular biology of the cuticle collagen gene families of Caenorhabditis elegans
      and Haemonchus contortus.

PMID- 1978528
TI  - Structure and expression of Ascaris suum collagen genes: a comparison with
      Caenorhabditis elegans.
AB  - We are interested in the structure and organization of collagen and collagen
      genes in the parasitic nematode Ascaris suum and in the control of collagen gene
      expression in Ascaris. In this nematode, as in all others studied, collagens
      constitute the major component of the extracellular cuticle and ultimately we
      would like to correlate the expression pattern of Ascaris cuticular collagen
      genes with the structure of the nematode cuticle. We would also like to see if
      there is any correlation between differential collagen gene expression and the
      biology and life-cycle of the parasite. In addition, we are also interested in
      comparing our data with the more extensive data available on collagen genes in
      the free living nematode Caenorhabditis elegans.

PMID- 1978529
TI  - The cuticular biology in developmental stages of Ascaris suum.
AB  - The cuticles from distinct developmental stages of Ascaris suum were isolated by
      a combination of mechanical disruption and detergent treatment of larvae or by
      surgical removal of cuticle from adults. Proteins from the isolated cuticles were
      solubilized with SDS and 2-mercaptoethanol (2ME) and analyzed by PAGE. Cuticular
      proteins from the third and fourth larval stages (L3 and L4) were comparable to
      adult, but differences in the number of bands were observed. The soluble proteins
      from the adult, L3 and L4 were readily degraded by bacterial collagenase,
      suggesting that these proteins are collagen-like structural elements of the
      cuticle. The soluble proteins from the L2 differed from the adult and other
      larval stages in both the number and molecular weight of protein bands and their
      lack of collagenase sensitivity. Antibodies made against the soluble cuticular
      proteins reacted with the medial and basal layers of the cuticle but not the
      external cortical or epicuticular regions. A significant amount of the cuticle
      was not solubilized by 2ME and was not digested by bacterial collagenase. These
      insoluble cuticular proteins were probably derived from the epicuticular and
      external cortical regions of the cuticle. Different developmental stages of A.
      suum were biotinylated and examined by electron microscopy. An organic soluble
      biotin reagent labeled all stages in a transcuticular pattern, while an aqueous
      soluble biotin labeled only the external cortical and epicuticular regions of the
      L4 and adult cuticle. These data indicate the presence of a hydrophobic barrier
      in the cuticle of later stages of the parasite.

PMID- 1978530
TI  - Analysis of the cuticular collagens of Ascaris suum.
AB  - The nematode cuticle is an extracellular structure composed mainly of collagens,
      with an insoluble epicuticle on the surface. The extracted collagens from adult
      Ascaris suum can be separated by SDS-PAGE into three major groups of polypeptides
      with apparent molecular masses of 34, 60-70 and 120-140 kDa. Densitometric
      evaluation of the polypeptide bands indicated that the three groups are present
      in the ratio of 1:2:6. Rotary shadowing of reduced, extracted molecules showed
      fibers 45 nm in length. This length is in excellent agreement with the calculated
      total length of amino acids in (Gly-X-Y) regions deduced from the collagen gene
      sequence of Caenorhabditis elegans and A. suum. It is proposed that the three
      groups of collagen polypeptides found in SDS-PAGE correspond to collagen
      monomers, dimers and trimers, and that the molecules in the dimeric and trimeric
      forms are cross-linked via non-reducible bonds.

PMID- 1978531
TI  - Identification of different radiolabelled antigens of the developmental stages of
      Onchocerca volvulus.
AB  - By using radioiodination methods which are thought to label preferentially the
      surface followed by SDS-PAGE and autoradiography, components of different
      developmental stages of O. volvulus have been identified. Between 2 and 10
      polypeptide antigens were revealed on infective larvae (L3), females, males,
      eggs, nodular and skin microfilariae by using immunoblotting assays with human
      onchocerciasis sera. Antigen recognition did not vary with the density of skin
      microfilariae in the patients from whom the sera were obtained. Some of the
      antigens seemed to be stage specific; for example, antigens of 31 kDa which were
      detected only on skin microfilariae, or the 67.5 and 25 kDa components that
      occurred on the adult females, but were absent from adult males. Some of these
      antigens were also identified as glycoproteins. A 68 kDa glycoprotein was found
      in adult females, males and nodular microfilariae. Two glycoproteins of 74 and 45
      kDa were found on egg shells, and a 18.5 kDa glycoprotein was recovered from L3.
      Type VI collagen was found with a specific antiserum on skin microfilariae, but
      not on eggs and females. Laminin was found on nodular mf. It is concluded that
      the changing antigenic profiles of the worm stages and the coating of these worms
      with connective tissue epitopes contribute to the evasion of host immunity.

PMID- 1978532
TI  - The surface lipid of parasitic nematodes: organization, and modifications during
      transition to the mammalian host environment.
AB  - The biophysical properties of the surface lipid of a range of nematode species
      and their developmental stages were examined, using fluorescent lipid probes and
      fluorescence recovery after photobleaching (FRAP). These methods can be applied
      to living, intact parasites, and the analysis confined to lipid on the outermost
      surface. In all cases, surface lipid was unusual in its selectivity for the
      insertion of the lipid probes. In addition, a polar lipid probe was generally not
      free to diffuse in the plane of the surface, in contrast to a non-polar lipid
      probe which was free to diffuse. This is evidence that the surface lipid layer is
      heterogeneous, and possibly comprises lipid domains. The infective larvae of
      Acanthocheilonema viteae, Nippostrongylus brasiliensis, Trichinella spiralis and
      Ostertagia ostertagi were found to exhibit a rapid change in lipophilicity upon
      exposure to conditions simulating entry into a mammalian host environment.
      Parasitic nematodes, therefore, present their hosts not only with a highly
      unusual biological surface, but also one which can be rapidly re-organised upon a
      change of environment.

PMID- 1978533
TI  - Antibodies against the cuticlin of Ascaris suum cross-react with epicuticular
      structures of filarial parasites.
AB  - The insoluble cuticlin from the cortical zone of the cuticle of adult Ascaris
      suum was purified and used to raise antibodies in C57/bl mice. The specificity of
      the antibodies for the external cortical layer was shown in the indirect
      immunofluorescence antibody test and by immunoelectronmicroscopy. A very high
      specificity for the external cortical layer was found. Some cross-reactions with
      cuticular collagens occurred, and increased after booster immunizations. The anti
      cuticlin antibody cross-reacted with the electron-dense layers of the cortical
      zones of adult Acanthocheilonema viteae and Brugia pahangi. A very weak reaction
      was found in the cortical zone of adult Onchocerca volvulus. In the cuticles of
      third stage larvae of all three species mainly epitopes in the cortical zones
      were labelled. In no case did the anti-cuticlin antibody interact with the
      outermost surface of the cuticle.

PMID- 1978535
TI  - Surface associated glycoproteins from Toxocara canis larval parasites.
AB  - The surface of infective larvae of Toxocara canis, the dog ascarid nematode,
      reveals relatively few exposed surface proteins which can be recovered in soluble
      form. The major components identified by surface labelling have molecular weights
      of 32, 55, 70 and 120 kilodaltons (kDa), and are all significantly glycosylated.
      All are recognised by the immune response in definitive (canine) and paratenic
      (murine or human) hosts. Expression of these antigens on the parasite surface
      begins after the larvae hatch from infective ova in vitro, and presumably in
      vivo. Each of these molecules may also be found in the set of secreted (ES)
      glycoconjugates released by larval parasites cultivated in vitro, and currently
      available biochemical and functional data on the surface/secreted ES
      glycoproteins are presented. Analysis with monoclonal antibodies (MAbs) confirms
      the identity of surface and ES molecules, and these MAbs show differing patterns
      of binding to the epicuticle, the cuticular matrix and to the oral orifice.
      Alternative mechanisms for antigen synthesis, insertion into the cuticle and
      export from the parasite are discussed.

PMID- 1978534
TI  - Surface-associated antigens of second, third and fourth stage larvae of
      Dirofilaria immitis.
AB  - The surface-associated molecules of the second (L2), third (L3) and fourth (L4)
      larval stages of Dirofilaria immitis were characterized employing radiolabeling
      techniques and SDS-PAGE analysis. Major labeled components of 35 kDa and 6 kDa
      were present in extracts from IODO-GEN-labeled L2 and L3 parasites. The results
      of lactoperoxidase-catalyzed reactions also demonstrated that L2 and L3 stages of
      D. immitis have a similar repertoire of surface-associated antigens. However, in
      contrast to the results obtained with IODO-GEN, lactoperoxidase reactions labeled
      components with apparent molecular weights of 66, 48, 25, 16.5 and 12 kDa. The
      similarities in the molecular weights of the L2 and L3 surface-associated
      components and the results of immunoprecipitation experiments which demonstrated
      that antibodies produced against the 35 kDa molecule from D. immitis L3s also
      recognize the 35 kDa component from L2 parasites suggest that synthesis of the
      molecules found at the surface of mature infective larvae begins as early as day
      6 of development in the mosquito, D. immitis L4s emerged from the molting process
      with a repertoire of surface-associated antigens distinct from those found on L2s
      and L3s. IODO-GEN labeling of D. immitis L4s showed major surface-associated
      molecules with apparent molecular weights of 57, 40, 25, 12 and 10 kDa when
      analyzed under non-reducing conditions. In addition to molecules of 57, 40, 25,
      12 and 10 kDa, extracts of D. immitis L4s labeled with lactoperoxidase contained
      additional major bands at 45, 43 and 8 kDa. Metabolic labeling experiments
      demonstrated a shift in the amount and complexity of the excretory/secretory
      products released by D. immitis during L3 to L4 development.

PMID- 1978536
TI  - The analysis of the 30 kDa antigen of Brugia pahangi and its interaction with the
      cuticle: a short review.

PMID- 1978537
TI  - Cuticular proteins of Brugia filarial parasites.
AB  - Surface-labelling techniques have been used to delineate a number of constituent
      molecules of the cuticle in adult stage Brugia malayi and Brugia pahangi. These
      molecules can be separated by virtue of their physical properties, and localised
      either by sequential solubilisation of intact cuticles or immunoelectron
      microscopy with relevant antisera. The major structural components of the
      cuticular matrix consist of a set of collagenous proteins of diverse molecular
      weight ranging from 36 to 160 kDa, cross-linked by disulphide bonds and confined
      to the basal and inner cortical layers. Each stage of the parasite has a
      distinctive set of between 12 to 25 collagenous proteins whose synthesis is
      regulated temporally with respect to moulting. As in other nematodes, the outer
      cortex and epicuticle is composed of a cross-linked insoluble proteinaceous
      structure. Two non-structural and water-soluble proteins are also resolved by
      Iodogen-mediated labelling; a 15 kDa peptide which shows no evidence of
      glycosylation, and a major 29 kDa glycoprotein, which carries at least two N
      linked oligosaccharide chains and which we have termed Gp29. The former protein
      can be detected in L3, L4 and adult B. malayi by surface labelling, whereas Gp29
      appears to be restricted to L4 and adult worms. The possible significance of
      cuticular proteins as targets of immunity or causative agents of pathology is
      discussed.

PMID- 1978538
TI  - Interaction of monoclonal antibodies with cuticular antigens of filarial
      parasites, Brugia malayi and Wuchereria bancrofti.
AB  - Monoclonal antibodies (mAbs) have been prepared against excretory-secretory
      metabolic (ESM) antigens of microfilariae (mf) of Wuchereria bancrofti (WbmfESM)
      and against third stage larvae (L3) of Brugia malayi (BmL3), and purified from
      ascites fluids with ammonium sulphate. Both antibodies were of the IgM type and
      did not react with phosphorycholine. The mAb against BmL3 (F46) reacted in ELISA
      with antigens of L3 of B. malayi, B. pahangi and W. bancrofti and of adults of B.
      malayi. The mAb raised against wbmfESM (F32) resembled F46 in this respect,
      though with a lower titer towards the antigens, and in addition reacted with the
      ESM-antigens of mf and of L3 of W. bancrofti. F46 was able to detect L3 antigens
      of filarial parasites in spiked serum samples with a detection limit of 8-16 ng
      in absolute amount. The antibody was found to label the cuticular portion of L3
      and adults of the lymphatic parasites, and not the epicuticular surface, in
      immunoelectron microscopic studies. The antibody recognized a 36 kDa component of
      the beta-mercaptoethanol extracts of B. pahangi-adults in Western blot analysis.

PMID- 1978539
TI  - Immunologic relevance of the cuticle and epicuticle of larval Dirofilaria immitis
      and Toxocara canis.
AB  - Investigations of the immunobiology of tissue stages of larval nematodes reveal
      several common, immunologically relevant features associated with the cuticle and
      epicuticle. First, commonality exists between surface and excretory-secretory
      antigens. Second, larval surfaces are often directly involved in evasion of host
      immune responses. Third, antigens present on the parasite surface can be involved
      in immunopathology, either directly through tissue damage or via systemic
      immunomodulatory events. Finally, in some instances, correlations can be inferred
      between immune protection and surface antigens. These concepts are illustrated
      through research on larval Dirofilaria immitis and Toxocara canis.

PMID- 1978540
TI  - The epidemiological significance of the immune response to the cuticular collagen
      of Necator americanus: a preliminary study in a hookworm-endemic area in Papua
      New Guinea.

PMID- 1978541
TI  - Patient profiling: individualization of hypertension therapy.
AB  - Although the stepped-care approach remains the cornerstone of antihypertensive
      therapy, the patient's profile must also be considered. Important issues include
      the patient's age, race and activity level, potential for hypertensive
      complications, presence of other diseases, cost of medications and probability of
      adherence to the recommended drug regimen. Nonpharmacologic treatment based on
      lifestyle changes is a useful adjunct to drug therapy, but it is not sufficient
      to control hypertension in most patients. Selection of pharmacologic therapy must
      be based on a knowledge of each drug's mode of action and side effects, as well
      as the characteristics of special patient populations.

PMID- 1978543
TI  - Cardiovascular imaging in the 1990s. Proceedings of a symposium. Grand Cayman
      Islands, April 6-7, 1990.

PMID- 1978542
TI  - PMA's concerns about therapeutic substitutions.

PMID- 1978544
TI  - Triggering and circadian variation of onset of acute cardiovascular disease. A
      symposium. Boston , Massachusetts, February 25, 1989 and Phoenix, Arizona, May 5
      6, 1989. Proceedings.

PMID- 1978545
TI  - Beta blockers and the primary prevention of nonfatal myocardial infarction in
      patients with high blood pressure.
AB  - A population-based, case-control study was conducted to determine whether beta
      blockers, used for the treatment of high blood pressure, prevent first events of
      coronary heart disease. All study subjects were health-maintenance organization
      enrollees with pharmacologically treated hypertension. Patients presented in 1982
      to 1984 with new coronary heart disease, and control subjects were a probability
      sample of eligible hypertensive enrollees free of coronary heart disease. With
      the investigators blind to case-control status, the subjects' medical records
      were reviewed for other coronary risk factors, and the health-maintenance
      organization's computerized pharmacy database was used to ascertain the use of
      beta blockers. A larger proportion of controls than cases were using beta
      blockers. This difference was confined to the subgroup with nonfatal myocardial
      infarctions. For current use, the estimated relative risk for nonfatal myocardial
      infarction was 0.62 (95% confidence interval, 0.39 to 0.99). Among current users
      of beta blockers, higher doses conferred greater protection. Past use and total
      lifetime intake of beta blockers were only weakly associated with case-control
      status. The current use of beta blockers may prevent first events of nonfatal
      myocardial infarction in patients with high blood pressure.

PMID- 1978546
TI  - Beta-blocker duration of action and implications for therapy.
AB  - Two studies were conducted to measure the effect of serum half-life on beta
      blocker-related heart rate reduction throughout the 24-hour period. In the first
      study, nadolol, atenolol and pindolol were associated with significant (p less
      than 0.01) heart rate reduction even at 24 hours after dose. Nadolol, with a
      plasma half-life of 15.5 hours, had the most pronounced heart rate-lowering
      effect 24 hours after the daily dose compared to pindolol, which had a half-life
      of 5.5 hours. In a randomized, double-blind, crossover study, nadolol and
      atenolol had similar effects 3 to 4 hours after the daily dose. Nadolol, however,
      produced greater suppression of heart rate and double product (blood pressure x
      heart rate) than atenolol (compared to placebo) 24 hours after ingestion of the
      daily dose. On ambulatory electrocardiography 24 hours after medication
      administration, 80 to 100% of the heart rate-attenuating effect of nadolol was
      maintained versus only 20 to 45% of atenolol's effect. Statistically significant
      (p less than 0.05) reductions in heart rate were produced by nadolol, but not by
      atenolol, between 4 and 5 A.M., 6 and 7 A.M., 8 and 9 A.M. and 9 and 10 A.M.
      Furthermore, nadolol remained at 52% of peak blood level at 24 hours, whereas
      atenolol was at 20%. The data from these 2 studies indicate that significant
      differences in duration of action exist between beta blockers.

PMID- 1978547
TI  - Effect of beta-adrenergic blocking agents on the circadian occurrence of ischemic
      cardiovascular events.
AB  - Clinical observations suggest that beta-adrenergic blocking agents can modify the
      circadian occurrence of a variety of ischemic events. Morning awakening is
      associated with a rapid increase in blood pressure and pulse, serum catecholamine
      content and platelet activation, at a time of decreased blood thrombolytic
      activity. Beta-adrenergic blocking agents have the potential to modify many of
      these events. Current data indicate that these agents modify blood pressure and
      pulse, but do not prevent their early morning increase. In addition, beta
      adrenergic blocking agents decrease ventricular ectopy and its circadian
      variation. Recent studies in humans indicate, however, that metoprolol does not
      affect the circadian increase in platelet activity or serum catecholamines. The
      specific mechanism by which beta blockers affect the circadian occurrence of
      ischemic events remains uncertain.

PMID- 1978548
TI  - Reduction of mortality, sudden death and non-fatal reinfarction with beta
      adrenergic blockers in survivors of acute myocardial infarction: a new hypothesis
      regarding the cardioprotective action of beta-adrenergic blockade.
AB  - Beta-adrenergic blockers have been shown definitely to reduce the incidence of
      total mortality, cardiovascular mortality, sudden death and nonfatal reinfarction
      in survivors of an acute myocardial infarction. The mechanisms to explain this
      protective action of beta blockers have never been elucidated conclusively, and
      include the antiarrhythmic and myocardial oxygen demand-reducing effects of the
      drugs. An antithrombotic mechanism has also been suggested. However, beta
      blockers have relatively weak antiplatelet activity, suggesting that their
      antithrombotic effects may be related to prevention of coronary artery plaque
      rupture and the subsequent propagation of an occlusive arterial thrombus rather
      than direct anticoagulant action. The therapeutic ability of beta blockers to
      attenuate the hemodynamic consequences of catecholamine surges, may protect a
      vulnerable atherosclerotic plaque from fracture, thereby reducing risk of
      coronary thrombosis, myocardial infarction and death.

PMID- 1978549
TI  - Subgroups of patients with atypical circadian patterns of symptom onset in acute
      myocardial infarction.
AB  - Circadian variation of onset of acute myocardial infarction has been noted in
      many studies and may carry important implications. However, only a few previous
      studies have attempted subgroup analysis. In 4,796 patients with documented acute
      myocardial infarction, the time of symptom onset was recorded. As in other
      studies, a peak occurred in the morning hours from 6 A.M. to noon with 28% of the
      population (1.16 times the average percent for the other time periods)
      experiencing symptom onset in that period (p less than 0.001). There was a second
      lower peak (25%) in the evening hours between 6:01 P.M. and midnight, also
      observed in some previous studies. Whether the presence of subgroups with
      specific clinical characteristics would exhibit different patterns and thereby
      contribute to these peaks in the overall population was then determined. In
      patients with a history of congestive heart failure (n = 606) or with non-Q-wave
      infarction (n = 832), a pronounced peak (29%) occurred only in the evening hours.
      In patients greater than 70 years of age (n = 1,422), smokers (n = 2,057),
      diabetics (n = 767), women (n = 1,213) and patients taking beta blocking drugs (n
      = 847), 2 nearly equal peaks were observed. Finally, in patients with previous
      myocardial infarction (n = 1,104), no peaks were observed. In a subgroup of
      patients (n = 1,084) free from the most important modifying factors, there was a
      single very pronounced late morning peak (32%), 1.39 times the average percent
      for the other time periods (p less than 0.001), without evidence of a second
      evening peak.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1978550
TI  - Effects of qing-fei-tang on the airway inflammation and clearance.
AB  - Qing-Fei-Tang, a Chinese blended medicine, inhibited the release of slow reacting
      substance of anaphylaxis (SRS-A) from passively sensitized guinea pig lung after
      antigen challenge. Qing-Fei-Tang also suppressed the chemiluminescence of oxygen
      radicals when healthy human leukocytes were stimulated by opsonized zymosan. In
      rabbits, Qing-Fei-Tang increased the output volume and fatty acid contents in
      respiratory tract fluid. In the bronchitic rabbits, 6 weeks administration of
      Qing-Fei-Tang restored the decreased amount of saturated fatty acid in the sputa,
      and histological examinations revealed an amelioration of the inflammation of
      lung tissues. In pigeons, Qing-Fei-Tang facilitated tracheal mucociliary
      transport. Accordingly, Qing-Fei-Tang seems to exert effectiveness via its
      multiple mechanisms.

PMID- 1978551
TI  - Longitudinal study of 94 symptomatic infants with perinatally acquired human
      immunodeficiency virus infection. Evidence for a bimodal expression of clinical
      and biological symptoms.
AB  - To better define the clinical and biological evolution of infants after vertical
      human immunodeficiency virus type 1 infection, we analyzed 94 consecutive
      infected patients followed up after their first clinical symptoms. The expression
      of clinical symptoms and biological abnormalities followed a bimodal
      distribution, some patients having an early and severe disease and the others
      having a slowly progressive one. One third of our patients suffered from early
      onset of opportunistic infection (OI). These patients had a significantly higher
      incidence of severe encephalopathy compared with patients without OI. The rate of
      survival at 3 years was 48% +/- 24%. In contrast, the patients without early OI
      or severe encephalopathy had a probability of survival at 3 years of 97% +/- 3%.
      This probability was not modified by the occurrence of bacterial infection or
      lymphoid interstitial pneumonitis. Lymphoid interstitial pneumonitis occurred at
      a mean age of 29 months, significantly later than OI or severe encephalopathy.
      Laboratory results at initial examination were correlated with clinical symptoms.
      Thus, when the number of CD4 lymphocytes was less than 500/mm3, children suffered
      more frequently from life-threatening symptoms (OI and severe encephalopathy): 15
      of 22 vs 14 of 69. The same was true when the lymphocytes did not proliferate
      after antigenic stimulation, when anti-p18 and/or anti-p25 antibodies were absent
      in the serum, and when p24 antigen was detected in serum. Finally, severe
      encephalopathy was associated with low anti-human immunodeficiency virus
      cerebrospinal fluid antibody titer, whereas 88% of patients with moderate or no
      encephalopathy had signs of intrathecal anti-human immunodeficiency virus
      antibody synthesis. In conclusion, a subgroup of patients expressed very early
      signs of severe immunodeficiency and encephalopathy, whereas the majority of
      patients had a longer survival and less severe clinical symptoms during their
      first years of life than previously thought.

PMID- 1978552
TI  - Somatostatin analogues and pancreatic acinar cell carcinoma: an alternative in
      symptomatic treatment?

PMID- 1978553
TI  - A termination mutant prevalent in Norwegian haplotype 7 phenylketonuria genes.
AB  - RFLPs in the phenylalanine hydroxylase (PAH) gene locus were determined in 47
      Norwegian nuclear families that had at least one child with phenylketonuria
      (PKU). The PKU haplotype distribution differed somewhat from that of other
      European populations. Mutant haplotype 7 is relatively rare in other populations
      but constituted 20% of all mutant haplotypes in Norway. In 14 of the 17 mutant
      haplotypes 7, a previously unreported deletion of the BamHI restriction site in
      exon 7 of the PAH gene was observed. The abrogation of the BamHI site was shown
      to be due to a G-to-T transversion, changing Gly 272 to Ter 272 in exon 7 of the
      gene, thus directly identifying the PKU mutation. Unlike the families of the
      other PKU patients, the families with this mutation clustered along the
      southeastern coast of Norway, suggesting a founder effect for this mutation.

PMID- 1978554
TI  - The NT 1311 polymorphism of G6PD: G6PD Mediterranean mutation may have originated
      independently in Europe and Asia.
AB  - A polymorphic site exists in exon 11 of G6PD: in the wild-type enzyme, nucleotide
      (NT) 1311 is a C, but is some individuals from diverse populations a T is present
      instead. Nine of 54 X chromosomes from Europeans of mixed origins, nine of 41 X
      chromosomes of Ashkenazi Jewish subjects, three of 18 X chromosomes of Sicilians,
      five of 20 African X chromosomes, and nine of 20 Asian Indian X chromosomes had
      the mutant genotype. In contrast, the mutation was found in only three of 59
      Oriental X chromosomes and in three of 30 Central/South American X chromosomes.
      The mutation was absent from four samples of chimpanzee DNA. Twenty-one of 22
      male subjects from Mediterranean countries who had the G6PD Mediterranean 563T
      genotype investigated in the present study or reported previously had a T at NT
      1311. Only one had the normal C at NT 1311. In contrast, both G6PD
      Mediterranean563T males from the Indian subcontinent had the normal C at NT 1311.
      These findings suggest that the same mutation at nucleotide 563 giving rise to
      G6PD Mediterranean may have arisen independently in Europe and in Asia.

PMID- 1978556
TI  - 1989 Allen Award address: the American Society of Human Genetics annual meeting,
      Baltimore.

PMID- 1978555
TI  - Origin and spread of the glucose-6-phosphate dehydrogenase variant (G6PD
      Mediterranean) in the Middle East.
AB  - A common glucose-6-phosphate dehydrogenase (G6PD) variant characterized by severe
      enzyme deficiency and B-like electrophoretic mobility is called "G6PD
      Mediterranean" because it is found in different populations around the
      Mediterranean Sea. Sequence analysis of Italian subjects has revealed that the
      molecular basis of G6PD-Mediterranean is a single C-T transition at nucleotide
      position 563, causing a serine phenylalanine replacement at amino acid position
      188. Most G6PD-Mediterranean subjects also have a silent C-T transition (without
      amino acid replacement) at nucleotide position 1311. Twenty-one unrelated
      individuals from Saudi Arabia, Iraq, Iran, Jordan, Lebanon, and Israel with both
      severe G6PD deficiency and B-like electrophoretic mobility were tested for both
      mutations by using amplification followed by digestion with appropriate
      restriction enzymes. All but one had the 563 mutation, and, of these, all but one
      had the 1311 mutation. Another 24 unrelated Middle Eastern individuals with
      normal G6PD activity or not known to be G6PD deficient were similarly tested.
      Four had the silent mutation at position 1311 in the absence of the deficiency
      mutation at position 563. We conclude that (1) the large majority of Middle
      Eastern subjects with the G6PD-Mediterranean phenotype have the same mutation
      found in Italy, (2) the silent mutation is an independent polymorphism in the
      Middle East, with a frequency of about .13, and (3) the mutation leading to the
      G6PD-Mediterranean deficiency has probably arisen on a chromosome that already
      carried the silent mutation.

PMID- 1978557
TI  - 1989 Allen Award address: the American Society of Human Genetics annual meeting,
      Baltimore.

PMID- 1978558
TI  - Nucleus-driven multiple large-scale deletions of the human mitochondrial genome:
      a new autosomal dominant disease.
AB  - We studied several affected and one nonaffected individuals belonging to three
      unrelated pedigrees. The pathological trait was an autosomal dominant
      mitochondrial myopathy due to large-scale multiple deletions of the mitochondrial
      genome. Clinically, symptomatic patients had progressive external
      ophthalmoplegia, muscle weakness and wasting, sensorineural hypoacusia, and, in
      some cases, vestibular areflexia and tremor. The muscle biopsies of all patients
      examined showed ragged-red fibers, neurogenic changes, and a partially decreased
      histochemical reaction to cytochrome c oxidase. Multiple mtDNA heteroplasmy was
      detected in the patients by both Southern blot analysis and PCR amplification,
      whereas the unaffected individual had the normal homoplasmic hybridization
      pattern. These findings confirm and add further details to the existence of a new
      human disease--defined clinically as a mitochondrial myopathy, genetically as a
      Mendelian autosomal dominant trait, and molecularly by the accumulation of
      multiple, large-scale deletions of the mitochondrial genome--that is due to
      impaired nuclear control during mtDNA replication.

PMID- 1978559
TI  - Isolation of a marker linked to the Charcot-Marie-Tooth disease type IA gene by
      differential Alu-PCR of human chromosome 17-retaining hybrids.
AB  - We report the isolation of a new marker (S6.1) from band p11.2 of human
      chromosome 17 by differential Alu-polymerase chain reaction (Alu-PCR) of both a
      monochromosomal hybrid retaining a single human chromosome 17 and a hybrid
      retaining a del(17)(p11.2p11.2) in addition to other human chromosomes. The
      method is based on the preferential PCR amplification of human DNA in
      rodent/human hybrids when primers specific to the human Alu repeat element are
      used. MspI and SstI RFLPs associated with S6.1 were identified and used in
      linkage analysis of both a previously reported and a newly identified French
      Acadian kindred segregating autosomal dominant Charcot-Marie-Tooth disease (CMT).
      A cumulative peak lod score of 3.41 at a peak recombination fraction of .12
      indicates that this marker is linked to the CMT 1A locus but is at a distance
      from the disease gene. Thus, the marker S6.1 will be useful in further
      delineating the candidate region for the CMT gene when its location with respect
      to pA10-41 and 1516, two other markers from 17p11.2 which have previously
      demonstrated close linkage to the CMT locus, has been determined.

PMID- 1978560
TI  - The mutation for medullary thyroid carcinoma with parathyroid tumors (MTC with
      PTs) is closely linked to the centromeric region of chromosome 10.
AB  - Two new morphs (F and G) detected by the centromeric alpha satellite probe p
      alpha 10RP8 and D10Z1 in HinfI digests are linked to the PstI polymorphisms of
      D10Z1, confirming their chromosome 10 location. The F and G morphs were in strong
      linkage disequilibrium with each other but were in weak linkage disequilibrium
      with the A and B morphs defined in PstI digests. Data for haplotypes formed by
      using the A and F morphs improved the lod score for linkage between the disease
      locus for multiple endocrine neoplasia type 2A (MEN2A) and D10Z1 (Z = 14.06 at
      theta = 0) in the six large families studied by Wu et al. Furthermore, the locus
      that codes for a distinct phenotype, medullary thyroid carcinoma (MTC) with
      parathyroid tumors (PTs) and no pheochromocytomas (PHEOs) (referred to as MTC
      with PTs), in one of the families was closely linked to two markers, D10Z1 and
      RBP3, with lodscores of 2.86 and 3.54, respectively, at theta = 0. A possible
      allelic association was noted between disease phenotypes and centromeric
      haplotypes. The phenotype MTC and PHEOs with and without PTs was associated with
      the same relatively common centromeric haplotype (A + B-F-G-) in the four
      families in which all four morphs could be determined, while the phenotype MTC
      with PTs was associated with the rare centromeric haplotype (A-B-F-G+) in one
      family.

PMID- 1978561
TI  - A new DNA marker (D10S94) very tightly linked to the multiple endocrine neoplasia
      type 2A (MEN2A) locus.
AB  - Combined somatic cell hybrid and linkage studies between D10S94 and five
      pericentromeric loci (FNRB, D10Z1, MEN2A, RBP3, and D10S15) have localized the
      new DNA sequence pcl1/A1S-6-c23 at D10S94 to 10q11.2. No recombinants were
      observed between D10S94 and D10Z1 or MEN2A. D10S94 maps in proximal 10q11.2 very
      near to MEN2A. There are three possible orders for the six loci that we
      investigated from the centromeric region of chromosome 10. At present the genetic
      data do not allow us to order MEN2A with respect to D10Z1 and D10S94. The three
      possible orders are FNRB-D10Z1-D10S94-MEN2A-RBP3-D10S15, FNRB-D10Z1-MEN2A-D10S94
      RBP3-D10S15, and FNRB-MEN2A-D10Z1-D10S94-RBP3-D10S15. In view of the fact that no
      recombinants between D10S94 and MEN2A or between D10S94 and D10Z1 were observed,
      the combined haplotypes formed from RFLPs and D10Z1 and D10S94 will increase the
      informativeness and accuracy of genotype prediction for at-risk members of the
      families having the MEN 2A syndrome, particularly when the affected parent is
      female. The localization of D10S94 with respect to MEN2A will prove valuable in
      experiments directed toward cloning the MEN2A locus.

PMID- 1978562
TI  - Analysis of DNA polymorphisms suggests that most de novo dup(21q) chromosomes in
      patients with Down syndrome are isochromosomes and not translocations.
AB  - Down syndrome is rarely due to a de novo duplication of chromosome 21 [dup(21q)].
      To investigate the origin of the dup(21q) and the nature of this chromosome, we
      used DNA polymorphisms in 10 families with Down syndrome due to de novo dup(21q).
      The origin of the extra chromosome 21q was maternal in six cases and paternal in
      four cases. Furthermore, the majority (eight of 10) of dup(21q) chromosomes were
      isochromosomes i(21q) (four were paternal in origin, and four were maternal in
      origin); however, in two of 10 families the dup(21q) chromosome appeared to be
      the result of a Robertsonian translocation t(21q;21q) (maternal in origin in both
      cases).

PMID- 1978563
TI  - Localization of the human angiogenin gene to chromosome band 14q11, proximal to
      the T cell receptor alpha/delta locus.
AB  - The gene encoding angiogenin, a potent inducer of blood vessel formation, has
      been localized within the human genome. It is present as a single copy per
      haploid genome and is located on chromosome 14, on the basis of discordancy
      analysis of human-rodent hybrid cell lines. This localization was refined to
      14q11 by in situ hybridization of an angiogenin probe to metaphase chromosomes
      prepared from both normal human lymphocytes and RPMI 8402 cells. The results from
      the RPMI 8402 cells also establish that the angiogenin gene resides proximal to a
      translocation breakpoint within the T cell receptor alpha/delta locus and
      therefore upstream from that locus. An AvaII RFLP, present at a frequency of 29%
      in an unselected collection of human placental DNAs, was identified in the coding
      region of the gene and results from a single silent transversion.

PMID- 1978564
TI  - Genetic linkage map of six polymorphic DNA markers around the gene for familial
      adenomatous polyposis on chromosome 5.
AB  - A genetic linkage map of six polymorphic DNA markers close to the gene (APC) for
      familial adenomatous polyposis (FAP) on chromosome 5q is reported. One hundred
      fifty-five typed members of nine FAP kindred provided more than 90 meioses for
      linkage analysis. A number of crucial recombination events have been identified
      which are informative at three or more loci, allowing confident ordering of parts
      of the map. There was no evidence of genetic heterogeneity, with all families
      showing linkage of at least one chromosome 5 marker to the gene. Recombination
      data and two-point linkage analysis support a locus order of centromere-pi 227
      C11P11-ECB27-L5.62-APC-EF5.44-YN5.48-telomer e, although EF5.44 could lie in the
      interval L5.62-APC or ECB27-L5.62. No recombinants were identified between APC
      and either EF5.44 or YN5.48, but published deletion mapping in colorectal
      carcinomas and linkage analysis in FAP suggest that YN5.48 is 1-3 cM from APC.
      The present study suggests that YN5.48 and L5.62 delineate a small region of
      chromosome 5 within which the EF5.44 locus lies very close to the APC gene. These
      data not only allow use of flanking markers for presymptomatic diagnosis of FAP
      but also provide a high-density map of the region for isolation of the APC gene
      itself and for further assessment of the role of chromosome 5 deletions in the
      biology of sporadic colorectal cancer.

PMID- 1978565
TI  - The human CYP2D locus associated with a common genetic defect in drug oxidation:
      a G1934----A base change in intron 3 of a mutant CYP2D6 allele results in an
      aberrant 3' splice recognition site.
AB  - The debrisoquine polymorphism is a common genetic defect that results in
      deficient oxidation of debrisoquine and numerous other drugs. These compounds are
      metabolized by a form of cytochrome P450, designated CYP2D6. Some 5%-10% of
      Caucasians are unable to metabolize debrisoquine, because of mutant alleles of
      CYP2D6. A CYP2D6 allele was isolated from leukocyte DNA of an individual who was
      deficient in debrisoquine metabolism. The gene was completely sequenced,
      including 725 bp of upstream and 400 bp of downstream DNA. Several base changes
      were uncovered within the exons, resulting in four amino acid differences between
      the mutant and wild-type allele. Most important, a single base change G1934----A
      at the junction of the third intron and four exon would result in an incorrectly
      spliced primary transcript and in an mRNA having a single base deletion. This
      deletion presumably disrupts the mRNA reading frame, resulting in a truncated
      protein. These data establish unequivocally that the debrisoquine polymorphism is
      the result of mutant CYP2D6 alleles and provide a framework to design a genetic
      test for this drug oxidation deficiency. A defective CYP2D7 allele was also
      isolated and completely sequenced, providing evidence that gene conversions have
      occurred between CYP2D6 and CYP2D7.

PMID- 1978566
TI  - Developing improved observational methods for evaluating therapeutic
      effectiveness.
AB  - Therapeutic efficacy is often studied with observational surveys of patients
      whose treatments were selected nonexperimentally. The results of these surveys
      are distrusted because of the fear that biased results occur in the absence of
      experimental principles, particularly randomization. The purpose of the current
      study was to develop and validate improved observational study designs by
      incorporating many of the design principles and patient assembly procedures of
      the randomized trial. The specific topic investigated was the prophylactic
      effectiveness of beta-blocker therapy after an acute myocardial infarction. To
      accomplish the research objective, three sets of data were compared. First, we
      developed a restricted cohort based on the eligibility criteria of the randomized
      clinical trial; second, we assembled an expanded cohort using the same design
      principles except for not restricting patient eligibility; and third, we used the
      data from the Beta Blocker Heart Attack Trial (BHAT), whose results served as the
      gold standard for comparison. In this research, the treatment difference in death
      rates for the restricted cohort and the BHAT trial was nearly identical. In
      contrast, the expanded cohort had a larger treatment difference than was observed
      in the BHAT trial. We also noted the important and largely neglected role that
      eligibility criteria may play in ensuring the validity of treatment comparisons
      and study outcomes. The new methodologic strategies we developed may improve the
      quality of observational studies and may be useful in assessing the efficacy of
      the many medical/surgical therapies that cannot be tested with randomized
      clinical trials.

PMID- 1978567
TI  - Parental origin of chromosome 5 deletions in the cri-du-chat syndrome.
AB  - The parental origin of de novo deletions leading to the cri-du-chat syndrome has
      been investigated. Since the cri-du-chat syndrome is correlated with deletions
      involving the short arm of chromosome 5 (5p), DNA fragments known to detect
      restriction fragment length polymorphisms (RFLPs) along 5p were used to establish
      whether the paternal or the maternal chromosome had suffered the deletion. In
      cases where only one parent was available, somatic cell hybrids were used in
      conjunction with RFLP analysis to determine the origin of the deleted chromosome.
      The deleted chromosome 5 was of paternal origin in 20/25 cases.

PMID- 1978568
TI  - Pulsatile GnRH in clinical medicine. A symposium. Fort Myers, Florida, January
      20, 1990. Proceedings.

PMID- 1978570
TI  - Effect of oxygen tension on catecholamine-induced formation of cAMP and on
      swelling of carp red blood cells.
AB  - We studied the effects of beta-adrenergic stimulation on the formation of
      adenosine 3',5'-cyclic monophosphate (cAMP) and on the cell volume in carp red
      blood cells in normoxia (PO2 = 150 mmHg) and hypoxia (PO2 = 8 mmHg). Accumulation
      of cAMP was the prerequisite for adrenergic cell swelling. Cell swelling was
      induced by beta-agonists, forskolin, and 8-bromo-cAMP. The amount of cAMP
      required for adrenergic swelling was minimal; swelling was observed at cAMP
      concentrations greater than 100 nM. Maximal increase in cell volume was observed
      at 200 nM cAMP. These values were independent of both the oxygen tension and the
      beta-agonist used. Norepinephrine caused the largest accumulation of cAMP,
      followed by isoproterenol and epinephrine. At hypoxic conditions, the cAMP
      concentrations obtained after stimulation with the natural catecholamines
      norepinephrine and epinephrine were greater than at normoxic conditions. The
      catecholamines caused appreciable cell swelling at lower concentrations in
      hypoxia than in normoxia. Thus the number of beta-adrenergic receptors, and their
      inherent ligand affinities, may be higher in hypoxic than in normoxic carp red
      blood cells. Oxygen tension had a pronounced effect on the magnitude of the
      adrenergic swelling. The maximal increase in cell volume was 5-7% in hypoxia,
      whereas in normoxia it was only approximately 2%. This was not due to differences
      in cAMP formation, but possibly to a greater activity of the Na(+)-H+ exchanger
      in hypoxic than in normoxic conditions.

PMID- 1978569
TI  - Expression of aminopeptidase N (CD13) in mesenchymal tumors.
AB  - For a long time, CD13 molecules have been considered to be restricted to myeloid
      cells and related neoplasms. Meanwhile, however, expression of CD13 has also been
      detected in some hepatocellular, gallbladder, renal, and lung carcinomas, and
      even in some fibrosarcomas and malignant melanomas. In this study, expression of
      CD13 antigen was immunohistochemically examined in non-neoplastic mesenchymal
      cells, along with 33 benign and 83 malignant mesenchymal tumors (MET) using CD13
      monoclonal antibodies (MAb) My7, U71, WM-15, and MoU48. In non-neoplastic
      mesenchymal cells, expression of CD13 was restricted to perivascular
      fibrocytes/blasts, tissue histiocytes, osteoclasts, and to the perineurium of
      peripheral nerve trunks. Under neoplastic conditions, CD13 was detectable in some
      tumors of smooth muscle, fibrous, fibrohistiocytic, synovial, osteogenic, and
      peripheral nerve sheath origin, and even in some tumors of adipose tissue. Tumors
      of striated muscle origin, of autonomic ganglia, and of cartilage-forming tissues
      were CD13-negative throughout. Thus in most but not all tumors studied the
      pattern of expression of CD13 mirrors the situation found in their cells of
      origin. These findings enrich the data on expression of leukocyte differentiation
      antigens in extra-hematopoietic tissues. Expression of CD13, which meanwhile is
      known to be identical to aminopeptidase N, an important peptide-cleaving enzyme,
      in only some MET might reflect a special functional state of these neoplasms.

PMID- 1978571
TI  - Regulation of postprandial motility in the canine ileum.
AB  - We describe here further observations on a novel motor phenomenon that can be
      recorded regularly from the canine ileum in the late postprandial period, i.e.,
      when residue of a meal reaches the distal small bowel. We reported before that
      this unique pattern of motility consisted of intraluminal pressure waves at a
      frequency (20-24/min) much greater than that of the ileal slow wave. In the
      current experiments, we document that these intraluminal pressure waves coincide
      with contraction of the circular muscle layer, as recorded from serosal strain
      gauges. However, the cellular origin and propagation of these contractile events
      are still unclear. By studying dogs with ileal loops and those with an intact
      bowel, we conclude that this is a local response of the ileum to the arrival of
      nutrients in its lumen and that it is under cholinergic control. This report
      supports the concept that the ileum may be particularly sensitive to its local
      intraluminal environment.

PMID- 1978572
TI  - Evidence that dopamine-2 mechanisms control renal function.
AB  - Dopamine is synthesized by the kidney, and dopamine-2 (DA2) receptors are present
      in the renal glomerulus. However, no role for DA2 receptors in the kidney has
      been defined. We investigated the possible role of DA2 receptors in control of
      renal function by intrarenal infusion of a highly specific DA2 antagonist YM
      09151 (YM), in conscious uninephrectomized dogs (n = 5) in metabolic balance at
      Na intake 40 meq/day. YM infused at 0.01 pmol.kg-1.min-1 did not cause any
      changes in urinary flow rate or Na excretion. Administration of YM (infusions
      from 0.1 to 10.0 pmol.kg-1.min-1) caused a significant dose-dependent diuresis (F
      = 20.3; P less than 0.001) and natriuresis (F = 35.2; P less than 0.0001) and an
      increase in glomerular filtration rate (F = 45.4; P less than 0.0001), renal
      plasma flow (F = 209.3; P less than 0.0001), and filtration fraction (F = 11.2; P
      less than 0.0001). No significant changes in plasma renin activity, plasma
      aldosterone concentration, or mean arterial blood pressure occurred with any of
      the doses of YM infused into the renal artery. Coinfusion of LY-171555, a
      specific DA2 agonist, at a dose that itself did not affect renal function,
      completely abrogated the renal hemodynamic and excretory changes induced by YM.
      The data suggest that dopamine produced intrarenally may act at renal vascular
      and/or glomerular DA2 receptors to control renal function.

PMID- 1978573
TI  - Quantitative and autoradiographic analyses of alpha-adrenergic and serotonergic
      receptors on aorta and coronary artery.
AB  - Norepinephrine, epinephrine, and 5-hydroxytryptamine (5-HT) modulate the vascular
      tone via specific receptors on the vascular wall. Binding characteristics and
      localization of alpha-adrenergic and serotonergic receptors were determined in
      porcine aortas and coronary arteries. Radioligand binding studies were done using
      frozen sections of vascular tissue (10 microns thick), and the obtained data were
      compared with findings on microsomal fractions prepared from smooth muscle cells.
      Affinities [dissociation constant (Kd)] of 125I-labeled 2-[beta-(4-hydroxyphenyl)
      ethylaminomethyl]-tetralone (BE 2254), an alpha 1-antagonist, for alpha
      adrenergic receptors on aortic and coronary microsomal fractions were 190 and 224
      pM, respectively. The Kd of 125I-labeled lysergic acid diethylamide (LSD), a
      serotonergic antagonist, to serotonergic receptors on the aorta was 403 pM, a
      value less than that obtained for the coronary artery (873 pM, p less than 0.01).
      The Kd of 125I-BE 2254 on tissue sections from the aorta was 164 pM and did not
      significantly differ from that obtained for microsomal fractions. Inhibition
      constants of adrenergic agonists and antagonists for specific 125I-BE 2254
      binding on aortic sections were identical with those obtained for microsomal
      fractions. Receptor densities examined by 125I-BE 2254 and 125I-LSD were higher
      in the aorta than in the coronary artery. 125I-BE 2254 bound specifically to
      alpha 1-adrenergic and 125I-LSD to 5-HT1-like receptors. Radiodensities of 125I
      BE 2254 and 125I-LSD were homogeneous macroscopically across the aortic media.
      Silver grains distributed homogeneously over the smooth muscle cells across the
      media. There was no accumulation of silver grains to the intima.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1978574
TI  - Cardiac responses to electrical stimulation of discrete loci in canine atrial and
      ventricular ganglionated plexi.
AB  - The purpose of the present study was to examine cardiac effects induced by
      electrical stimulation (1-4 V, 1 ms, 200 Hz) of discrete loci within the
      ganglionated plexi located on canine atria and ventricles. When 20 loci in the
      right atrial ventral ganglionated plexi of 11 anesthetized open-chest dogs were
      stimulated, bradycardia and/or right and left atrial force suppression occurred
      when, on average, 15% of these loci were stimulated. Bradycardia and atrial force
      suppression were elicited when, on average, 8% of 15 loci in the left atrial
      ventral ganglionated plexi of eight dogs was stimulated. When these loci were
      restimulated after acute decentralization, cardiac responses were attenuated or
      occasionally eliminated. After atropine (1 mg/kg iv) administration, repeat
      stimulation of loci in the right but not left atrial ganglionated plexus induced
      tachycardia. Stimulation of loci in the right ventricular ganglionated plexus
      after the subsequent administration of desipramine (1 mg/kg iv) in six dogs
      resulted in an increase in right ventricular conus intramyocardial pressure.
      After hexamethonium administration (10 mg/kg iv, followed by a continuous
      infusion of 1 mg.kg-1.min-1), sympathetic responses were no longer elicited from
      one of the five dogs in which loci in the right atrial ganglionated plexi and
      from two of the six dogs in which loci of the right ventricular ganglionated
      plexus had elicited responses. We conclude that atrial and ventricular
      ganglionated plexi contain efferent parasympathetic, efferent sympathetic, and
      afferent neurons.

PMID- 1978576
TI  - Autoradiographic delineation of skeletal muscle alpha 1-adrenergic receptor
      distribution.
AB  - We used light microscopic autoradiography to quantify the distribution of alpha 1
      adrenergic receptors in vessels and muscle fibers of slow-twitch (type I), fast
      twitch (types IIa and IIb), and mixed fiber muscles of the rat hindquarter.
      Frozen cross sections of soleus, vastus lateralis, and gastrocnemius muscles were
      incubated under equilibrium binding conditions with 10-200 pM [3H]prazosin with
      or without 10(-5) M phentolamine. Because of the low concentration of bound
      radioligand, specific binding could not be detected with scintillation
      spectrometry in whole tissue sections scraped from slides. However, quantitative
      autoradiographic analysis after extended intervals of emulsion exposure revealed
      a low but significant level of specific binding in muscle fibers. No difference
      in alpha 1-receptor density was observed among types I, IIa, and IIb fibers.
      Small blood vessels had a much greater alpha 1-receptor density than muscle
      fibers. Resistance arterioles (20-100 microns diam) and small arteries (100-500
      microns diam) contained 5.8 +/- 0.9 and 31.6 +/- 7.6 (+/- SE) times more binding
      sites per unit section area, respectively, than did surrounding muscle fibers
      (both P less than 0.001). Ratios of specific grain densities in fibers and blood
      vessels did not vary with radioligand concentration, indicating that observed
      grain densities reflected differences in receptor concentration rather than
      radioligand affinity by fiber and vessel receptors. The densities of vascular
      alpha 1-receptors did not vary in slow- and fast-twitch muscles, but resistance
      arterioles were six and eight times more numerous in soleus than in gastrocnemius
      and vastus muscles, respectively (both P less than 0.001).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1978575
TI  - Excitatory amino acid receptors of guinea pig medial nucleus tractus solitarius
      neurons.
AB  - Neurons isolated from the medial subnuclei of nucleus tractus solitarius in adult
      guinea pigs were studied for responses to the excitatory amino acid glutamate and
      its analogues using the whole cell tight-seal voltage clamp technique. In 80% of
      the cells studied (n = 60) 100 microM glutamate produced inward currents at
      negative voltages. To further characterize the glutamate response, the agonists
      for three glutamate receptor subtypes, N-methyl-D-aspartate (NMDA), kainate, and
      quisqualate, were examined for their effects on membrane conductance. NMDA (25
      250 microM) activated currents in 85% of the neurons tested (n = 30). NMDA
      currents were generally very small in amplitude. Of the neurons tested, 84%
      responded to kainate (10-30 microM, n = 19) and only 50% to quisqualate (25-50
      microM, n = 26). The conductance activated by NMDA was outwardly rectifying. The
      conductance activated by kainate was voltage independent, while that activated by
      quisqualate showed varying degrees of outward rectification. Responses to NMDA
      were specifically antagonized by DL-2-amino-5-phosphonovaleric acid (AP-5, 50-100
      microM). Kainate responses were blocked by kynurenate at concentrations (0.5-1.5
      mM) ineffective on quisqualate-induced current. Glutamic acid diethyl ester
      (GDEE, 2-15 mM) was effective in reducing quisqualate responses at concentrations
      that had no effect on kainate responses. This characterization of the glutamate
      receptor subtypes and effective antagonists provides a basis for future
      determination of the specific receptor of glutamate responsible for mediation of
      the excitatory postsynaptic potentials produced by activation of the baroreceptor
      input.

PMID- 1978577
TI  - Parasympathetic postganglionic pathways to the sinoatrial node.
AB  - Vagal ganglia that innervate the canine sinoatrial node (SAN) have been localized
      to a fat pad overlying and surrounding the right pulmonary vein complex (PVFP).
      The ventral epicardial surface of the right atrium was mapped in seven dogs
      anesthetized with alpha-chloralose after beta-blockade (timolol) and cardiac
      sympathetic and parasympathetic decentralization. A small, concentric bipolar
      exploring electrode was used to stimulate (during the atrial refractory period
      and using trains of five to eight stimuli per beat) systematically in the
      epicardial regions between the PVFP and the SAN. Changes in SAN rate with
      stimulation were measured, and the anatomic location was identified on a 150
      point grid fitted to conform to size and shape of the atrium. Mapping was
      performed before and after local (PVFP) and systemic ganglionic blockade
      (hexamethonium). Data reveal that the primary vagal postganglionic pathways to
      the sinoatrial nodal region are subepicardial and adjacent to the SAN artery
      along the sulcus terminalis. Hexamethonium in the PVFP abolishes SAN inhibition
      during preganglionic vagal excitation, without interrupting vagal suppression of
      atrioventricular conduction. However, SAN slowing (with varying attenuation)
      continued to occur after hexamethonium (either PVFP or systemically) when the
      exploring electrode was applied directly over intramural postganglionic fibers
      between PVFP and sinus node. Attention is directed to existence of a very few
      synapses closer to SAN, probably in isolated ganglia immersed in fatty connective
      tissues along the sulcus terminalis.

PMID- 1978578
TI  - Beta-receptor subtypes in the canine coronary circulation.
AB  - The principal difficulty in determining the subtype of coronary vascular beta
      receptors in vivo is to avoid the local metabolic coronary vasodilation that
      occurs secondary to activation of myocardial beta-receptors. Therefore, a
      nonbeating cardiac preparation without chronotropic or inotropic effects is
      needed. In this study, the coronary circulation was perfused at constant pressure
      in closed-chest chloralose-anesthetized dogs. The increase in coronary blood flow
      due to intracoronary injections of the combined beta 1- and beta 2-agonist
      isoproterenol was determined during prolonged asystoles after the cessation of
      cardiac pacing in atrioventricular heart-blocked animals. Both beta 1-selective
      (practolol and L 650,744) and beta 2-selective (ICI 118,551) antagonists blocked
      isoproterenol-induced coronary vasodilation. In contrast, isoproterenol
      vasodilation in the femoral circulation was blocked by beta 2- but not by beta 1
      selective antagonists. In conclusion, both beta 1- and beta 2-receptors in
      coronary resistance vessels are stimulated by isoproterenol to produce
      vasodilation during prolonged asystoles, when cardiac chronotropic and inotropic
      effects are absent.

PMID- 1978579
TI  - Catecholamines depress endolymphatic sac direct current potential in guinea pigs.
AB  - To test the possibility that catecholamines have an influence on the function of
      the endolymphatic sac (ES), which is known to absorb the endolymph, the effect of
      catecholamines on the ES direct current potential (ESP) was examined in the
      guinea pig. The ESP was recorded extradurally by the posterior occipital
      approach. Isoproterenol (Iso), epinephrine (Epi), and norepinephrine (NE) were
      administered intravenously for 4 min using an infusion pump. Catecholamines
      reversibly depressed the ESP with the rank order of potency Iso greater than Epi
      greater than NE. The threshold doses were 0.021, 0.27, and 1.94 micrograms/kg for
      Iso, Epi, and NE, respectively. beta-Antagonist (propranolol) blocked the action
      of catecholamines on the ESP but alpha-antagonist (phentolamine) did not. This
      indicates that beta-adrenergic action induces the ESP change. This study implies
      that catecholamines may regulate the function of the ES.

PMID- 1978580
TI  - Mechanisms of pressor response produced by stimulation of nucleus ambiguus.
AB  - We showed previously that activation of nucleus ambiguus (NA) induced bradycardia
      and increased arterial pressure. In this study, we compared responses produced by
      electrical and chemical (glutamate) stimulation of NA and adjacent rostral
      ventrolateral medulla (RVLM). Equivalent pressor responses were elicited from
      both areas. However: 1) The response from RVLM was elicited at a lower frequency.
      2) Regional vascular resistance changes were different, i.e., electrical
      stimulation of NA increased vascular resistance in hindquarters much more than
      the renal and mesenteric beds. In contrast, electrical and chemical stimulation
      of RVLM produced a more prominent effect on the renal vascular bed. 3)
      Bradycardia was elicited from NA at lower current intensity. 4) Glutamate
      produced bradycardia only when injected into NA. Studies in rats with sinoaortic
      deafferentation showed that bradycardic response to activation of NA was only
      partly reflex in origin. We conclude that 1) NA and RVLM control sympathetic
      outflow to regional vascular beds differentially and 2) the NA region involves
      parasympathetic control of heart rate and sympathetic control of arterial
      pressure.

PMID- 1978581
TI  - Benzodiazepine tranquilizers and the risk of accidental injury.
AB  - To determine whether benzodiazepine tranquilizers increase the risk of accidental
      injury requiring medical attention, we used pharmacy claims submitted to a large
      third-party payer to identify 4,554 persons who had been prescribed these agents
      and a matched control group of 13,662 persons who had been prescribed drugs other
      than benzodiazepines. We then used diagnoses recorded on claims submitted by
      medical care providers to identify all accident-related care received by these
      persons during three months before their first-observed prescription for a
      benzodiazepine or nonbenzodiazepine agent, respectively, and six months
      subsequently. We found accident-related care was more likely among persons who
      had been prescribed benzodiazepines; among these persons, the probability of an
      accident-related medical encounter was higher during months in which a
      prescription for a benzodiazepine had recently been filled compared to other
      months; and persons who had filled three or more prescriptions for these agents
      in the six months following initiation of therapy had a significantly higher risk
      of an accident-related medical event than those who had filled only one such
      prescription. Approximately two-fold risks of accident-related care were found,
      after controlling for age, sex, and prior utilization.

PMID- 1978583
TI  - [Infections of bones and joints. Prophylaxis--therapy--social, economic and legal
      aspects. 2nd edition].

PMID- 1978582
TI  - Effects of spermatic vascular division for correction of the high undescended
      testis on testicular function.
AB  - Orchiopexy with division of the spermatic artery and veins is a commonly used
      technique for correcting the high undescended testis, although the longterm
      results have not been clearly defined. The left spermatic artery and veins of 22
      adult Wistar albino rats were divided while preserving the vessels associated
      with the vas and cremaster muscle (DT). A sham operation was performed on the
      left testicle of six additional rats (ST). At 3 weeks postoperatively, both
      testes from all rats were removed. All testes were viable and bled when incised,
      although bleeding was considerably reduced in testes with DT. Mean testicular
      weights after DT were 1,061 +/- 423 mg compared with 1,634 +/- 125 mg for ST rats
      (p less than 0.02) and 1,508 +/- 119 mg for contralateral testes. The mean
      tubular diameter after DT was 220 +/- 37 mu compared with 303.1 +/- 10.7 mu for
      ST testes (p less than 0.02). The testicular biopsy score based upon the
      morphology of the spermatic tubules was 4.46 +/- 3.32 for DT testes and 8.65 +/-
      0.23 for ST testes (p less than 0.02) compared with 8.38 +/- 0.18 for
      contralateral testes and an absolute normal value of 10. No morphologic
      abnormalities were observed in the contralateral unoperated testes from any of
      the rats. The contralateral testes in 12 additional rats were removed before DT.
      The mean testosterone values in these rats with one testicle was 1.43 +/- 0.75
      ng/mL. Three weeks after DT, testosterone values were 0.19 +/- 0.31 ng/mL (p less
      than 0.01). It is concluded that division of the main spermatic artery and vein
      in rats produces testicular atrophy with spermatogenic arrest and interstitial
      cell dysfunction. Although collateral blood flow to the testis may be
      demonstrated, tissue perfusion is inadequate for normal spermatogenesis and
      endocrine function.

PMID- 1978584
TI  - [Use of a collagen-gentamicin compound in open spongiosaplasty in chronic post
      traumatic osteomyelitis].

PMID- 1978585
TI  - [Bone transplantation in post-traumatic osteitis].

PMID- 1978586
TI  - [Bone sterilization and bone disinfection].

PMID- 1978587
TI  - [Skin-plasties in osteitis].

PMID- 1978588
TI  - [Covering soft tissue defects with pedicled autochthonous muscle flap-plasty].

PMID- 1978589
TI  - [Microsurgical flap-plasty].

PMID- 1978590
TI  - [Quality control in bone infection].

PMID- 1978591
TI  - [Psychosocial problems from the viewpoint of psychosomatic medicine].

PMID- 1978592
TI  - [Malpractice for bone infection].

PMID- 1978593
TI  - [Economic aspects of bone infection].

PMID- 1978594
TI  - [Antibiotic therapy--what is certain?].

PMID- 1978595
TI  - [The biomechanics of osteosynthesis].

PMID- 1978596
TI  - [Therapy of acute osteitis].

PMID- 1978597
TI  - [Stability in post-traumatic osteitis].

PMID- 1978598
TI  - [Irrigation drainage in local treatment of infection of bones and joints].

PMID- 1978599
TI  - [Local treatment of infection with gentamicin-PMMA chains and minichains].

PMID- 1978600
TI  - [Treatment of local infection with taurolin].

PMID- 1978601
TI  - [Incidence of infection, causes and prevention of osteitis in trauma surgery].

PMID- 1978603
TI  - [Bioresorbable collagen-gentamicin compound as local antibiotic therapy].

PMID- 1978602
TI  - [Local treatment of infection with collagen gentamicin].

PMID- 1978605
TI  - Attenuation of suxamethonium myalgias. Effect of midazolam and vecuronium.
AB  - We studied the incidence of fasciculations and postoperative myalgias in 100
      female outpatients who had laparoscopy under thiopentone, N2O, isoflurane
      anaesthesia. Four groups of 20 patients each were pretreated with saline (group
      1), tubocurarine 0.05 mg/kg (group 2), vecuronium 0.006 mg/kg (group 3), or
      midazolam 0.025 mg/kg (group 4), followed by suxamethonium 1.5 mg/kg. Group 5
      received only vecuronium 0.1 mg/kg as relaxant (no suxamethonium). Fasciculations
      were graded, and postoperative myalgias rated on the first and third
      postoperative days. In groups 1-5 the incidence of fasciculations was 95, 15, 25,
      95 and 0%; the incidence of myalgias on the first day after operation was 70, 45,
      65, 75 and 60%, and on the third day after operation 20, 5, 20, 20, and 5%,
      respectively. We conclude that pretreatment with vecuronium, but not midazolam,
      decreases the incidence of fasciculations after suxamethonium (p less than 0.05)
      and that in this patient population, postoperative myalgias appear to be
      unrelated to the use of suxamethonium.

PMID- 1978604
TI  - A review of the biochemical pathways studied and abnormalities reported in the
      Rett syndrome.
AB  - A review of the current research on selected biochemical pathways and reported
      abnormalities in the Rett syndrome (RS) is presented. While RS has a clinical
      course that is similar to known metabolic diseases, consistent abnormal
      biochemical findings in RS patients have not been identified.

PMID- 1978606
TI  - Autonomic dysfunction and Guillain-Barre syndrome. The use of esmolol in its
      management.
AB  - A 17-year-old girl with Guillain-Barre syndrome and autonomic dysfunction was
      treated successfully with esmolol. Esmolol may be an appropriate drug for the
      rapid assessment and control of tachyarrhythmias in critically ill patients.

PMID- 1978607
TI  - Prolonged neuromuscular blockade with vecuronium in a neonate with renal failure.
AB  - An 11-day-old neonate with renal failure caused by dysplastic kidneys was
      anaesthetised with thiopentone, vecuronium, nitrous oxide and oxygen, for
      insertion of a long-term peritoneal dialysis catheter. Complete neuromuscular
      block of 210 minutes' duration ensued after the initial dose of vecuronium (97
      micrograms/kg). Partial block persisted for a further 30 minutes. The prolonged
      neuromuscular block in this case may have been because of proportionately greater
      dependence on renal clearance of vecuronium in neonates.

PMID- 1978608
TI  - Coated amperometric electrode arrays for multicomponent analysis.
AB  - This paper describes a sensor array of several amperometric electrodes, each
      coated with a different permselective film. Coatings with different transport
      properties, based on size (cellulose acetate), charge (Nafion,
      poly(vinylpyridine), poly(ester sulfonic acid], and polarity (phospholipid) are
      employed in connection with a four-electrode thin-layer flow detector. With
      equipotential operation, the array's response pattern of each analyte provides a
      unique characterization of the individual components. Multicomponent analysis is
      obtained by taking advantage of the partial selectivity of the individual sensors
      and using a pattern recognition (multiple linear regression) method. Additional
      information is obtained by recording the complete hydrodynamic voltammogram at
      the individual sensors. The merits of the new array are illustrated for the
      quantification of neurologically significant catechol compounds.

PMID- 1978609
TI  - Age-related immunohistochemical studies of A and D cells in pancreatic islets of
      C57BL/6J mice.
AB  - Sections of pancreatic islets from C57BL/6J mice aged 3, 14, and 24 months,
      consisting of islets derived from the dorsal primordium (DPI) and from the
      ventral primordium (VPI), were immunostained using the peroxidase-antiperoxidase
      (PAP) procedure for localization of glucagon (A cells) and somatostatin (D
      cells). The density (A or D cell area/islet area) of immunopositive cells were
      determined using computer-assisted image analysis. The density of A cells was
      significantly less in VPI of 14- and 24-month-old mice compared to 3-month-old
      mice. The density of A cells in 24 month DPI was less than 3 month DPI but no
      different from 14 month DPI. The mean area (microns 2) of A cells (only in DPI)
      was significantly less at 24 months compared to the 3 and 14 month groups. There
      were no differences in somatostatin staining when comparing the three age groups,
      although at all ages the density of D cells was always greater in the DPI. In
      conclusion, the major difference between the young and older mice was a
      deficiency of glucagon-stained cells in older mice. These results might be
      important in explaining improved glucose tolerance in aged C57BL/6J mice.

PMID- 1978610
TI  - Purification and properties of gamma-glutamyl transpeptidase from human testis.
AB  - Gamma-glutamyl transpeptidase was purified to apparent homogeneity from human
      testis by DEAE cellulose, acetone, precipitation, fractionation by ammonium
      sulphate, Sephacryl S-200 chromatography, Q-Sepharose chromatography and S
      Sepharose chromatography following solubilization of the enzyme by Triton X-100.
      The purified enzyme had an apparent molecular weight of 54 KDa by Sephacryl S-200
      gel filtration. On sodium dodecyl sulphate polyacrylamide gel electrophoresis,
      two submits of molecular weight 38 KDa and 14 KDa were obtained. The purified
      enzyme showed a single band with pI 6.0. The Km value and the optimal pH of the
      enzyme for L-gamma-glutamyl-3-carboxy-4-nitroanilide were found 1.09 mmol/l and
      8.2-8.5, respectively. Serial lectin binding study with various lectin columns
      showed that the majority of the asparagine-linked oligosaccharides of the enzyme
      was complex-types. However, complex-types with bisecting N-acetylglucosamine
      residue were not recognized.

PMID- 1978611
TI  - Testicular maldescent and infertility.
AB  - Testicular maldescent is one of the causes of male infertility. This paper
      illustrates that it was possible to determine that this pathology was present in
      8.96% of the cases in 212 men who consulted for infertility at our service during
      1987. When we compared clinical, hormonal and seminal studies with infertile
      subjects without testicular maldescent and with a group of 20 fertile patients,
      statistically significant differences were established, suggesting a poorer
      prognosis of fertility to the group with maldescent testes.

PMID- 1978612
TI  - Esmolol attenuates cardiovascular responses to extubation.
AB  - Changes in heart rate and systolic blood pressure were measured during extubation
      and emergence from anesthesia in 40 ASA physical status I and II patients in a
      double-blind study to assess the effect of three doses of esmolol (1, 1.5, and 2
      mg/kg) given as a bolus 2 min after reversal of neuromuscular blockade. Heart
      rate (P less than 0.01), systolic blood pressure (P less than 0.02), and rate
      pressure product (P less than 0.01) increased significantly during extubation of
      the control group. All doses of esmolol attenuated the increases in heart rate,
      but 1 mg/kg was insufficient to control the increase in systolic blood pressure.
      Doses of 1.5 and 2 mg/kg controlled both systolic blood pressure and heart rate,
      but the larger dose produced significant decreases in systolic blood pressure.

PMID- 1978613
TI  - Does perioperative tactile evaluation of the train-of-four response influence the
      frequency of postoperative residual neuromuscular blockade?
AB  - The authors conducted a randomized controlled clinical trial to evaluate the
      usefulness of perioperative manual evaluation of the response to train-of-four
      (TOF) nerve stimulation. A total of 80 patients were divided into four groups of
      20 each. For two groups (one given vecuronium and one pancuronium), the
      anesthetists assessed the degree of neuromuscular blockade during operation and
      during recovery from neuromuscular blockade by manual evaluation of the response
      to TOF nerve stimulation. In the other two groups, one of which received
      vecuronium and the other pancuronium, the anesthetists evaluated the degree of
      neuromuscular blockade solely by clinical criteria. The use of a nerve stimulator
      was found to have no effect on the dose of relaxant given during anesthesia, on
      the need for supplementary doses of anticholinesterase in the recovery room, on
      the time from end of surgery to end of anesthesia, or on the incidence of
      postoperative residual neuromuscular blockade evaluated clinically. The median
      (and range of) TOF ratios recorded in the recovery room were 0.75 (0.33-0.96) and
      0.79 (0.10-0.97) in the vecuronium groups monitored with and without a nerve
      stimulator, respectively. These ratios were significantly higher than those found
      in the pancuronium groups, which wre 0.66 (0.06-0.90) and 0.63 (0.29-0.95),
      respectively. However, no difference was found between the vecuronium and
      pancuronium groups in the number of patients showing clinical signs of residual
      neuromuscular blockade, as evaluated by the 5-s head-lift test.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1978614
TI  - Vecuronium neuromuscular blockade at the diaphragm, the orbicularis oculi, and
      adductor pollicis muscles.
AB  - To determine the relationship among diaphragm, orbicularis oculi, and adductor
      pollicis blockade, train-of-four stimulation was applied to the phrenic, facial,
      and ulnar nerves in 16 adult patients anesthetized with alfentanil-propofol
      oxygen. Vecuronium 0.04 or 0.07 mg/kg was given. The response of the adductor
      pollicis was measured with a force transducer, and that of the other muscles by
      electromyography (EMG). No statistically significant differences were detected
      with either dose in the intensity of maximum blockade measured at the three
      muscles. With 0.04 mg/kg, the first response (T1) in the train-of-four was
      decreased (mean +/- SEM) 78 +/- 8, 62 +/- 11, and 84 +/- 3% for the diaphragm,
      orbicularis oculi, and adductor pollicis, respectively. Corresponding values
      after 0.07 mg/kg were 95 +/- 3, 82 +/- 11, and 95 +/- 2%, respectively. However,
      onset time was longer at the adductor pollicis than at the diaphragm, and the
      orbicularis oculi onset time approached that of the diaphragm. With 0.04 mg/kg,
      time to maximum diaphragmatic blockade was 2.9 +/- 0.3 min, compared with 3.7 +/-
      0.6 min at the orbicularis oculi (no significant difference [NS]) and 6.6 +/- 0.4
      min at the adductor pollicis (P less than 0.001). With vecuronium 0.07 mg/kg the
      values were 2.2 +/- 0.3, 3.4 +/- 0.5 (P = 0.024), and 6.3 +/- 0.6 (P less than
      0.001), respectively. Time to 75% T1 recovery was similar at the diaphragm and
      the orbicularis oculi, but significantly longer at the adductor
      pollicis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1978615
TI  - Anesthesia for craniotomy: a double-blind comparison of alfentanil, fentanyl, and
      sufentanil.
AB  - Using a prospective, randomized, and double-blind study design, alfentanil (n =
      15), fentanyl (n = 14), or sufentanil (n = 16), in combination with N2O, were
      administered to patients undergoing craniotomy for supratentorial tumor
      resection. Physicians were given two syringes, one of which was labeled as "load"
      for the initial loading dose and the other as "maintenance" for continuous
      infusion. The concentration of drug in each syringe was adjusted to permit
      administration on a milliliter per kilogram basis. The target loading doses for
      alfentanil, fentanyl, and sufentanil were 75, 10, and 1 microgram/kg,
      respectively, and initial infusion rates were 33.5, 2.0, and 0.3 microgram.kg-1.h
      1, respectively. Additional supplementary boluses and changes in maintenance
      infusion rate were made according to predetermined guidelines. Isoflurane, in
      increasing 0.2% inspired increments, was used only when the maximum allowed
      opioid dose had been given (i.e., supplementary bolus doses equal to 75% of the
      calculated loading dose or supplementary bolus doses equal to 50% of the
      calculated loading dose combined with a 50% increase in the maintenance infusion
      rate). Opioid infusions were stopped at the time of bone flap replacement.
      Antihypertensive medications and naloxone were subsequently given at the
      discretion of the anesthesiologist. Group demographics were not different. Total
      volumes of drug were similar among groups indicating equipotent preparations.
      Administration of isoflurane, antihypertensive medications, and naloxone were not
      different among groups. Although decreases in blood pressure seen with induction
      were similar among groups, alfentanil-treated patients received ephedrine more
      frequently before intubation. Thirty minutes after entry into the postanesthesia
      recovery area, respiratory rate and pH were lowest in sufentanil-treated
      patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1978616
TI  - Effects of dexmedetomidine on contractility, relaxation, and intracellular
      calcium transients of isolated ventricular myocardium.
AB  - The effects of the highly selective alpha 2-adrenoceptor agonist dexmedetomidine
      on contractility, relaxation, and the intracellular Ca2+ transients of isolated
      ventricular myocardium were studied in isolated right ventricular papillary
      muscles obtained from reserpinized ferrets. Dexmedetomidine (10(-10)-10(-5) M)
      did not alter amplitude and time variables of isometric, isotonic and zero-load
      clamped twitches, except for a slight increase in maximal isotonic relaxation
      rate at 10(-5) M. Dexmedetomidine (10(-8)-10(-5) M) caused no changes in the
      intracellular Ca2+ transient detected with aequorin. These results suggest that
      dexmedetomidine has no intrinsic myocardial contractile effects.

PMID- 1978617
TI  - Ganglionic blockade improves neurologic outcome from incomplete ischemia in rats:
      partial reversal by exogenous catecholamines.
AB  - The authors investigated the effects of nitrous oxide (N2O), ganglionic blockade,
      and combined infusion of epinephrine and norepinephrine (0.1 microgram.kg-1.min-1
      each) on neurologic outcome and brain histopathology in a model of incomplete
      cerebral ischemia in the rat. Thirty-eight Sprague-Dawley rats were assigned to
      one of four groups: group 1 (n = 10) received 70% N2O in O2; group 2 (n = 12)
      received 70% N2O in O2, plus ganglionic blockade; and group 3 (n = 10) received
      70% N2O in O2, plus ganglionic blockade and catecholamine infusion. In groups 1
      3, ischemia was produced by right carotid occlusion combined with hemorrhagic
      hypotension (35 mmHg) for 30 min. Group 4 (n = 6) received 70% N2O in O2 and
      hemorrhagic hypotension without carotid occlusion for 30 min. At the end of
      ischemic and nonischemic hypotension, the carotid artery was unclamped and the
      blood slowly reinfused. Neurologic outcome was evaluated for a 5-day period with
      a graded deficit score (0 = normal to 39 = stroke-related death). Brain
      histopathology was evaluated in coronal section at the level of the caudate
      nucleus according to a 6-point scale, from 0 = normal to 5 = total hemispheric
      infarction. Arterial blood gases, pH, and body temperature were kept constant in
      all groups. Compared to N2O alone (group 1), treatment with ganglionic blockade
      (group 2) decreased plasma catecholamines by 75% and significantly improved
      neurologic outcome from incomplete cerebral ischemia (P less than 0.05).
      Administration of exogenous epinephrine and norepinephrine in the presence of N2O
      and ganglionic blockade (group 3) worsened neurologic outcome compared to group 2
      (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1978618
TI  - Molecular definition of the bovine granulocytopathy syndrome: identification of
      deficiency of the Mac-1 (CD11b/CD18) glycoprotein.
AB  - Leukocytosis (34,600 WBC/microliter of blood) was detected in an apparently
      healthy 7-day-old Holstein heifer. Analysis of blood samples obtained over the
      next 41 days revealed chronic progressive neutrophilia, which peaked at greater
      than 85% neutrophils and exceeded 100,000 WBC/microliter. In vitro assessment of
      isolated blood neutrophils obtained from the heifer at 38 and 45 days of age
      revealed selected functional abnormalities. Endocytosis of immunoglobulin
      opsonized Staphylococcus aureus and killing of this test organism by the calf's
      neutrophils were significantly diminished, as were phagocytosis-associated
      superoxide generation, chemiluminescence activity, and myeloperoxidase-catalyzed
      iodination. Diminished H2O2 elaboration by the calf's neutrophils was evident
      during ingestion of opsonized zymosan or on exposure to phorbol myristate
      acetate. Extracellular release (secretion) of elastase during ingestion of
      zymosan was also diminished, although total cell content of elastase was normal,
      compared with that of neutrophils from age-matched calves, and granular or other
      morphologic abnormalities of the calf's neutrophils were not evident by
      ultrastructural examination. Abnormalities of random migration were
      inconsistently detected, and normal or high degree of antibody-dependent
      cytotoxicity or natural killing by the calf's neutrophils was observed. Similar
      in vitro assessment of neutrophils obtained from the calf's dam revealed no
      functional abnormalities. The calf died at 48 days of age, with persistent fever
      and chronic diarrhea, despite administration of antibiotics. Histologic
      examination at necropsy revealed large numbers of intravascular neutrophils in
      most tissues, including massive neutrophil sequestration in spleen. However, a
      striking lack of extravascular neutrophils was evident in inflamed submucosa
      adjacent to intestinal ulcers heavily contaminated with enteric microorganisms.
      Bone marrow examination revealed diffuse myeloid hyperplasia, but no other
      abnormalities.

PMID- 1978619
TI  - Formoterol, a new inhaled beta-2 adrenergic agonist, has a longer blocking effect
      than albuterol on hyperventilation-induced bronchoconstriction.
AB  - The duration of effect of inhaled formoterol (24 micrograms) was compared with
      that of a placebo and that of inhaled albuterol (200 micrograms) in 12 adult
      asthmatic subjects who underwent hyperventilation tests with cold dry air (-20
      degrees C) on 4 study days. On the control day, they were subjected to four
      hyperventilation tests to ensure functional stability. On the 3 remaining days,
      after a first hyperventilation test, they inhaled placebo, albuterol, or
      formoterol in randomized, double-blind fashion. The hyperventilation test was
      repeated 1, 4, and 8 h and, if the blocking effect was still present, 12 and 24 h
      after the drug had been administered. The dose of hyperventilation of cold air
      causing a 20% fall in FEV1 (PD20) was interpolated on the dose-response curve.
      The magnitude of the blocking effect at each time interval on each study day was
      assessed by comparing the changes in PD20 from baseline with the within-day
      variability of PD20 (standardized change in PD20). The acute bronchodilator
      effect was not significantly different as assessed 15 min (21 +/- 14% for
      albuterol and 18 +/- 18% for formoterol) and 1 h (20 +/- 13% for albuterol and 18
      +/- 17% for formoterol) after administering the medication. The duration of the
      blocking effect, defined as the return to 2 SD from the standardized change in
      PD20, was significantly more prolonged for formoterol (8.0 +/- 3.4 h) than for
      albuterol (3.0 +/- 1.7 h) (t = 4.2, p less than 0.0001).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1978620
TI  - Low bone density is an etiologic factor for stress fractures in athletes.
AB  - OBJECTIVE: To determine whether low bone density and other risk factors for
      osteoporosis are associated with stress fractures in athletes. DESIGN: Case
      control study. SETTING: Institutional sports injury clinic with primary and
      secondary care. PARTICIPANTS: Twenty-five athletes (nineteen women) with
      scintigraphically confirmed stress fractures matched for sex, age, weight,
      height, and exercise history with 25 control athletes with no history of bone
      injury. MEASUREMENTS AND MAIN RESULTS: Bone mineral density measured by dual
      energy x-ray absorptiometry was significantly lower in athletes with fractures
      than in control athletes: In the spine, bone mineral density was 1.01 +/- 0.14
      g/cm2 in athletes with fractures and 1.11 +/- 0.13 g/cm2 in control athletes (P =
      0.02). In the femoral neck, it was 0.84 +/- 0.09 g/cm2 in athletes with fractures
      and 0.90 +/- 0.11 g/cm2 in control athletes (P = 0.005). It was also
      significantly lower in the Ward triangle (P = 0.01) and the greater trochanter (P
      = 0.01). Eight athletes with fractures and no control athletes had less than 90%
      of predicted age-related spine density (P = 0.01), and three athletes with
      fractures had bone mineral densities that were 2 SDs or more below this predicted
      level. More athletes with fractures than control athletes had current menstrual
      irregularity (amenorrhea or oligomenorrhea) (P less than 0.005). Fewer athletes
      with fractures were using oral contraceptives (P less than 0.05). Seven-day diet
      records indicated similar energy and nutrient intakes, except athletes with
      fractures had lower calcium intakes (697 +/- 242 mg/d compared with 832 +/- 309
      mg/d; P = 0.02). Dairy product intake was lower in athletes with fractures since
      leaving high school (P less than 0.05). The incidence of a family history of
      osteoporosis was similar in both groups. CONCLUSIONS: In athletes with similar
      training habits, those with stress fractures are more likely to have lower bone
      density, lower dietary calcium intake, current menstrual irregularity, and lower
      oral contraceptive use.

PMID- 1978621
TI  - Beta-blockers for cocaine-induced coronary vasoconstriction.

PMID- 1978623
TI  - [Anatomo-clinical conference. Pitie-Salpetriere Hospital. Case No. 3--1990. Fever
      and intermittent claudication of the lower limbs in a young Turkish woman with an
      aortic prosthesis].

PMID- 1978622
TI  - [Anti-H2 and omeprazole in brief therapy of peptic ulcer].

PMID- 1978624
TI  - [Continuity in the neuroleptic treatment in patients with schizophrenia. Current
      data].

PMID- 1978626
TI  - [Atopic dermatitis: role of oxatomide].
AB  - Oxatomide is an antiallergic molecule which acts mainly as a calcium blocker.
      This article is a review of oxatomide treatment in atopic dermatitis patients.
      First, an overview of oxatomide treatment hypersensitivity reactions in atopic
      dermatitis and of their supposed immunologic mechanisms. The total number of
      patients treated so far in published studies is too low to fully appreciate the
      therapeutic benefit of this molecule. However, encouraging results were reported
      in two controlled studies and 3 open studies originating from four different
      groups. Tolerance was excellent (of 200 patients evaluated in 5 studies,
      transient sleepiness was noted in 5, and weight gain was noted in 3 children).

PMID- 1978625
TI  - [Chronic urticaria: role of oxatomide].
AB  - Oxatomide (Tinset) is a new, powerful, antiallergic agent. Pharmacological and
      morphological studies have shown that oxatomide is not only an antihistaminic
      agent but it also inhibits mast cells and basophils degranulation, and neoformed
      mediators synthesis and release. Open and comparative studies have shown
      oxatomide to be an effective agent in the treatment of chronic urticaria
      including physical urticaria and food allergy. All these studies confirm its
      constant efficacy, giving good to excellent results in 68 to 89 percent of cases.
      It compares favorably with the classic anti-H1, particularly in that the
      symptomatic response is much quicker. Moreover the drug is always well tolerated,
      even when used at higher doses than those presently recommended (30 mg twice
      daily).

PMID- 1978627
TI  - [Oxatomide and calcium: mechanisms involved in the secretion of mast cell
      mediators].
AB  - Human cutaneous mast cells and their experimental model rat peritoneal mast
      cells, can be stimulated by an IgE-dependent process or by peptides through the
      direct activation of G proteins. Both activation pathways lead to the increase of
      cytosolic Ca2+ level. This increase in dependent of the mobilisation of
      intracellular calcium stores of the endoplasmic reticulum involving the
      stimulation of IP3-sensitive calcium channels. Mast cells are characterized by
      the absence of calcium channels in the plasma membrane. Oxatomide has been
      synthetized as an analog of cinnarizine. However oxatomide is inactive on current
      calcium channels. In mast cells, oxatomide inhibits the increase of cytosolic
      calcium elicited during mast cell activation. Consequently mast cell exocytosis
      is inhibited altogether with the release of newly synthetized mediators. The
      authors propose several putative targets for oxatomide in mast cells. The
      therapeutic effect of oxatomide is also related to its property to antagonize the
      effects of anaphylactic mediators on their selective receptors.

PMID- 1978628
TI  - Usher syndrome type I is not linked to D1S81 (pTHH 33): evidence for genetic
      heterogeneity.
AB  - Usher syndrome is an autosomal recessive disease associating congenital
      sensorineural deafness and retinitis pigmentosa. Two clinical forms have been
      recognized, namely a) congenital and severe (type I) and b) later and moderate
      (type II). A linkage of the D1S81 probe (THH 33) with the gene for type II has
      been recently demonstrated by Kimberling et al. 1990. Here, a panel of 29
      individuals from 6 kindreds with Usher syndrome type I has been tested for
      possible allelism at the D1S81 locus. A negative lod-score was found with this
      probe and close linkage to this region could be excluded. These different results
      support the view that the clinical heterogeneity in Usher syndrome is accounted
      for by an obvious genetic heterogeneity.

PMID- 1978629
TI  - A new DNA probe of potential use for diagnosis of the fragile-X syndrome.
AB  - A new cloned DNA probe (U6.2), which recognizes a TaqI polymorphism near the
      locus for the fragile-X syndrome, was tested in a great Xq-fra pedigree. In the
      corresponding four families studied, the probe is informative and no
      recombinations were observed between the probe and the disease locus, although
      recombinational events were observed with several other probes tested in the
      past. The locus defined by the probe, DXS304, cosegregated with the fragile-X
      phenotype in 20 informative meioses (z = 3.09, theta = 0.00). The degree of
      polymorphism at this locus and its proximity to the fragile-X locus makes it
      useful for diagnostic applications.

PMID- 1978630
TI  - A LDL receptor gene homozygous mutation: PCR amplification, direct genomic
      sequencing, associated haplotype, rapid screening for frequency.
AB  - Many mutations in the LDL receptor (LDLR) gene have now been identified mostly as
      gross gene rearrangements, however they only represent a weak percentage of all
      deleterious gene mutations causing Familial Hypercholesterolemia (FH). This
      discrepancy may be related to the difficulties in characterizing point or small
      defective mutations. In a three-generation family with Familial
      Hypercholesterolemia, one specific haplotype constructed with 12 intragenic
      restriction fragment length polymorphisms (RFLP) cosegregated with the disease,
      while in the consanguineous propositus there was homozygosity for this haplotype.
      By polymerase chain reaction (PCR) amplification followed by direct sequencing
      there was unequivocal evidence for a double dose of a unique mutation, (namely a
      duplication of 4 bases in exon 17), while there was a single dose in heterozygote
      relatives. We consequently screened a population selected under clinical and
      geographical criteria for this mutation by PCR and allele specific
      oligonucleotides (ASO) hybridization. None of the 158 type IIa individuals tested
      carried the same mutation. Herein, is a rapid combined genetic and molecular
      approach to characterize and evaluate the frequency of LDL Receptor gene
      mutations causing Familial Hypercholesterolemia, towards targeted prevention and
      therapy.

PMID- 1978631
TI  - CYP21B gene conversion and complete CYP21A gene deletion in congenital adrenal
      hyperplasia.
AB  - We studied a family in which one out of two children presented a non-salt wasting
      form of CAH. Genomic DNA of the patient, his brother, his parents and a normal
      control were digested by the Taq I and Bgl II restriction enzymes. The fragments
      were electrophoresed, transferred onto a nitrocellulose membrane and hybridized
      with two specific probes: pC21a for the CYP21 genes and pAT-A for the C4 genes.
      We performed simultaneous RFLP analyses of the CYP21 and C4 genes and determined
      the relative hybridization intensity of the genes using scanning densitometry of
      the X-ray films. The affected child had a CYP21B gene conversion in the CYP21A
      pseudogene on one chromosome inherited from his mother and a mutated CYP21B gene
      on the second chromosome inherited from his father. The second maternal
      chromosome, inherited by the unaffected brother, presented an unusual CYP21A gene
      deletion without a C4A or C4B gene deletion. Although CYP21A is a pseudogene,
      this type of complete CYP21A gene deletion associated with a CYP21B gene
      conversion has never been previously described.

PMID- 1978633
TI  - Clinical significance of multiple drug resistance in human cancers.
AB  - This review summarizes the basic aspects of multidrug resistance (MDR). We first
      propose a brief reappraisal of the occurrence of MDR encoded P-glycoprotein, (P-g
      P) in various normal and tumor tissues. We then present a series of studies
      undertaken to estimate the MDR1 gene expression or the presence of P-g-P in
      various human cancers. Finally, we conclude on the potential use of P-g-P
      measurements in some cancers as a useful if not powerful means of reversing
      clinical multidrug resistance.

PMID- 1978632
TI  - Immunohistochemical demonstration of growth factors, TGF-alpha, TGF-beta, IGF-I
      and neu oncogene product in benign and malignant human breast tissues.
AB  - The expression of growth factors, TGF-alpha, TGF-beta, IGF-I and neu oncogene
      product was studied immunohistochemically in the tissue of 120 benign and
      malignant human breasts. Growth factors were found only in benign or malignant
      mammary epithelial cells and not in stromal cells. Normal and benign lesions were
      found to be negative for reactivity with each antibody. Carcinoma in situ and
      invasive breast carcinomas demonstrated a significantly higher percentage of
      stained cells than that observed in benign lesions; forty (49%) of 82 invasive
      carcinomas were positive for TGF-alpha, 31 (38%) for TGF-beta, 31 (38%) for IGF-I
      and 34 (41%) for neu product. No overall correlations were found between
      expression of each growth factor and the clinical stage or degree of histologic
      differentiation of the carcinomas. A significant positive correlation was
      observed between ER status and IGF-I expression and between PgR status and TGF
      beta expression. In the majority of the carcinomas, co-expression between TGF
      alpha, TGF-beta and IGF-I was observed; the percentage of cases with parallel
      positive or negative expression of two growth factors was as follows; TGF-alpha -
      TGF-beta (70%), TGF-alpha - IGF-I (57%), TGF-beta - IGF-I (71%). The concomitant
      expression of TGF-alpha and neu oncogene product in cell surface was also
      observed. The relapse-free intervals of the patients were studied in association
      with expression of each growth factor. TGF-beta-positive tumors showed a
      significantly better prognosis than TGF-beta - negative tumors (within the first
      2 years of observation). However, TGF-alpha, IGF-I and neu overexpression showed
      no effect on the prognosis of the patients.

PMID- 1978634
TI  - Substantia nigra: a site of action of muscle relaxant drugs.
AB  - Sites of action of centrally active muscle relaxant drugs are not well defined.
      Clinical experience with such drugs suggests that the spinal cord may be one of
      the important regions from which pathologically increased muscle tone may be
      relieved. Supraspinal centers that may also be involved in the expression of
      muscle relaxant action have not yet been defined. We report here that
      microinjections of therapeutically relevant muscle relaxants into the midbrain
      tegmentum of genetically spastic rats decrease muscle tone. The substantia nigra
      is the region from which midazolam, baclofen, and tizanidine (drugs used
      clinically in the treatment of spasticity), or gamma-vinyl-GABA, (-)-2-amino-7
      phosphonoheptanoate, and [D-pro2-D-phe7-D-trp9]-substance P (experimental drugs
      active in animal models of spasticity), reduce muscle tone in genetically spastic
      rats and Hoffmann reflexes in normal rats. The effects of muscle relaxant drugs
      are topographically restricted to the substantia nigra pars reticulata and are
      receptor specific. These observations disclose a previously unknown function of
      the substantia nigra in mediating muscle relaxation.

PMID- 1978635
TI  - Effect of S-(2-chloroethyl)-DL-cysteine on the transport of p-aminohippurate ion
      in renal plasma membrane vesicles.
AB  - The effects of S-(2-chloroethyl)-DL-cysteine (CEC) (a potent nephrotoxin) on the
      transport of p-aminohippurate ion (PAH) in renal plasma membrane vesicles
      isolated from rat renal cortex were studied in vitro. The uptake of PAH was
      significantly reduced in a dose-dependent manner in both the brush border
      membrane (BBM) and basolateral membrane (BLM) vesicles. These results demonstrate
      that CEC is capable of interfering with the accumulation of PAH (a model organic
      anion for renal tubular transport system) by both energy-independent and energy
      dependent carrier-mediated transport processes. Probenecid, a typical inhibitor
      of the organic anion transport system, showed the highest inhibition of PAH
      uptake in both the membranes vesicles. These data indirectly suggest that
      transport by renal tubular cells may result in the accumulation of CEC in renal
      cellular organelles eventually in toxic concentrations. Thus, CEC showed both
      dose- and time-dependent inhibition of the activities of gamma-glutamyl
      transferase (a BBM marker enzyme) and Na+, K(+)-ATPase (a BLM marker enzyme),
      while no such inhibition was noticed with probenecid. Pretreatment with
      probenecid prevented the inhibition of the gamma-glutamyl transferase activity
      due to CEC in BBM, but failed to do so for the Na+,K(+)-ATPase activity in BLM
      vesicles. Thus, the data suggest that the inhibition of the activities of these
      membrane-specific enzymes by CEC could lead to the initial development of its
      nephrotoxicity.

PMID- 1978636
TI  - Simultaneous stimulation of fatty acid synthesis and oxidation in rat hepatocytes
      by vanadate.
AB  - When added to the hepatocyte incubation medium, vanadate increased the rate of
      fatty acid synthesis de novo as well as the activity of acetyl-CoA carboxylase,
      whereas it had no effect on the activity of fatty acid synthase. On the other
      hand, and despite elevating the intracellular levels of malonyl-CoA, vanadate
      diverted exogenous fatty acids into the oxidation pathway at the expense of the
      esterification route. This was concomitant to an increase in carnitine
      palmitoyltransferase I activity. All these effects were not significantly
      different between periportal and perivenous hepatocytes and were also evident in
      cells incubated in Ca2(+)-free medium. Nevertheless, Ca2+ ions enhanced carnitine
      palmitoyltransferase I activity in isolated liver mitochondria. In addition, the
      effects of vanadate on acetyl-CoA carboxylase and carnitine palmitoyltransferase
      I were only evident in a permeabilized-cell assay, disappearing upon cell
      disruption and isolation of the corresponding cell subfraction for enzyme assay.
      Results show that vanadate exerts specific insulin-like and non-insulin-like
      effects on hepatic fatty acid metabolism, and suggest that the intracellular
      concentration of malonyl-CoA is not the only factor responsible for the
      regulation of the fatty-acid-oxidative process in the liver.

PMID- 1978637
TI  - Sulfasalazine as folic acid inhibitor in psoriasis.

PMID- 1978638
TI  - Molecular characterisation of C4 null alleles found in Felty's syndrome.
AB  - A higher prevalence of C4B null alleles is found in Felty's syndrome. The
      molecular basis of C4 null alleles was investigated by studying restriction
      fragment length polymorphisms (RFLPs) obtained with C4 and 21-hydroxylase (21-OH)
      DNA probes and by pulsed field gel electrophoresis in 30 subjects with Felty's
      syndrome. C4A null alleles were found in 10 subjects, and in five of these were
      associated with a deletion that included C4A and adjacent 21-OHA gene sequences.
      A 6.4 kilobase C4B-5'-specific Taq I fragment usually provided a reliable guide
      to the presence of a C4A deletion but unusually in one instance this fragment was
      found to be a marker of a functioning C4A gene. A C4B null allele was found in 17
      subjects and was associated with a deletion involving C4B and 21-OHA gene
      sequences on only two occasions. There were no instances in which deletion of the
      21-OHB gene occurred.

PMID- 1978639
TI  - Thrombocytopenia due to aurothioglucose, sulphasalazine, and hydroxychloroquine.
AB  - A 56 year old woman with rheumatoid arthritis developed relapsing
      thrombocytopenia during successive treatments with aurothioglucose,
      sulphasalazine, and hydroxychloroquine. The presence of IgM or IgG antibodies or
      immune complexes reactive with autologous platelets could not be shown. Relapsing
      thrombocytopenia may indicate a genetically determined HLA-DR3 and B8 aberrant
      immunological response to stimuli such as certain second line drugs.

PMID- 1978640
TI  - Surgical management of pheochromocytoma with the use of metyrosine.
AB  - Despite recommended preoperative preparation with alpha-adrenergic blockers,
      severe hemodynamic instability may occur during operations to resect
      pheochromocytoma. We combined the alpha-blocker phenoxybenzamine with the
      tyrosine hydroxylase inhibitor metyrosine in an attempt to better manage the
      hypertension of patients with pheochromocytoma undergoing surgical resection.
      This report reviews the cases of 25 consecutive patients undergoing surgery for
      known intra-abdominal pheochromocytoma. Each patient had elevated serum or urine
      levels of catecholamines or their metabolites. Nineteen patients were prepared
      before operation with phenoxybenzamine and metyrosine and six patients were given
      phenoxybenzamine alone. There were no significant differences in maximum,
      minimum, or mean blood pressure before or after tumor resection between patients
      who received metyrosine and those who did not. However careful review suggested
      that those who received metyrosine had more severe disease as judged by
      biochemical criteria. Study of selected patients matched for age and severity of
      disease suggested that the intraoperative blood pressure management of patients
      prepared with phenoxybenzamine and metyrosine was facilitated. In addition
      metyrosine-prepared patients lost less blood and required less volume replacement
      during surgery than did non-metyrosine-prepared patients. There were no apparent
      differences in postoperative fluid requirements. Although the study is not a
      prospective randomized trial, a retrospective review of patients managed with the
      combination of phenoxybenzamine and metyrosine suggests that surgery to resect
      pheochromocytoma can be better performed with both drugs than with
      phenoxybenzamine alone. The combination regimen appears to result in better blood
      pressure control, less blood loss, and the need for less intraoperative fluid
      replacement than does the traditional method of single-agent alpha-adrenergic
      blockade.

PMID- 1978642
TI  - Selective and adjustable pericardial flap to protect internal mammary artery
      grafts.
AB  - We describe the surgical technique of a localized and adjustable pericardial flap
      to protect internal mammary artery grafts. This flap allows selective pulmonary
      retraction, maintains pleural integrity, and saves most of the pericardium for
      later closure. This technique has proved to be simple and highly effective. We
      have used it in 80 patients and have not had any related complications.

PMID- 1978641
TI  - Five-year results of coronary bypass grafting for patients older than 70 years:
      role of internal mammary artery.
AB  - Despite numerous references to the superiority of the internal mammary artery
      (IMA) over the saphenous vein for myocardial revascularization, its role in the
      elderly is still in question. From January 1984 through December 1988, 1,081
      patients older than 70 years (mean age, 74.9 years) underwent bypass grafting,
      354 (33%) receiving left IMA grafts based on the surgeon's preference and 727
      (67%) receiving vein grafts only. Selection bias resulted in a higher incidence
      of known risk factors (such as cardiomegaly, arrhythmias, left ventricular
      failure, wall motion abnormalities, and preoperative combined New York Heart
      Association/Canadian Cardiovascular Association functional class IV) in patients
      in whom the IMA was not used. However, unstable angina, acute myocardial
      infarction, left ventricular dysfunction, and left main disease were not
      contraindications for using IMA grafts. The operative mortality rate was
      significantly lower in IMA patients (2.8% versus 7.6%). The actuarial 5-year
      survival rate (standard error) was higher in patients with IMA grafts, 89% (3%)
      versus 78% (2%), and postoperative functional class improved to a greater extent
      in IMA patients (87% of patients were in classes I and II). Arrhythmias and
      myocardial infarction were significant causes of late death only in patients with
      vein grafts. When patients are older than 70 years, patient selection factors
      clearly play an important role in the differential results between patients in
      whom the IMA is used and patients in whom vein grafts are used. As in younger
      patients, excellent results can be achieved in the elderly.

PMID- 1978644
TI  - Desensitization of guinea-pig parenchymal lung strips after prolonged histamine
      H1-receptor stimulation.
AB  - In this study we examined the desensitization of guinea-pig parenchymal lung
      strips after excessive stimulation of the histamine H1-receptor. After
      stimulation with maximal effective concentrations of the selective H1-receptor
      agonist 2-pyridylethylamine (1 mM) for 30 min, subsequent 2-pyridylethylamine
      responses were inhibited as shown in a depression of the maximal response with
      approximately 40%. This desensitization was time- and concentration-dependent.
      Besides H1-receptor responses, potassium chloride (50 mM)-induced responses were
      also affected. Treatment of lung strips with 1 mM of 2-pyridylethylamine for 30
      min resulted in an inhibition of the potassium-induced contraction with 26.1 +/-
      8.7% of the control response. Desensitization of the lung strip preparation could
      not be prevented by the cyclooxygenase inhibitor indomethacin (20 microM),
      indicating that the observed inhibition is not due to an elevated production of
      relaxing prostaglandins. Desensitization was also not dependent on the influx of
      extracellular calcium. Stimulation of guinea-pig parenchymal lung strips with 1
      mM of 2-pyridylethylamine in a calcium-free buffer, supplemented with the calcium
      chelator EGTA, did not lead to observable contractions. However, desensitization
      still developed under these conditions. These data indicate that guinea-pig
      parenchymal lung strips exhibit a desensitized state after prolonged H1-receptor
      stimulation. Because this effect is not only limited to H1-receptor responses, as
      KCl effects are reduced as well, it should, at least partly, be explained by an
      interference with processes which occur distally to the H1-receptor itself.

PMID- 1978643
TI  - Action of stobadine on respiratory and vascular smooth muscle in vivo: evidence
      for histamine receptor antagonist activity.
AB  - The effect of stobadine on respiratory smooth muscles, blood pressure, heart rate
      and gastric acid secretion was studied and compared with the action of other
      antihistamines in vivo. Stobadine, as diphenhydramine, dithiadene and
      promethazine, but in contrast to cimetidine and ranitidine, prevented histamine
      from producing bronchospasm both after i.v. and oral administration. Based on the
      potency of its pharmacological action, diphenhydramine had a lower
      bioavailability after oral administration than the other antihistamines. Both
      cimetidine and ranitidine reduced the gastric acid secretion while stobadine was
      ineffective in this respect. None of the drugs studied antagonized histamine in
      reducing blood pressure, but all of them, with exception of promethazine and
      diphenhydramine, reduced mean arterial blood pressure. The results suggest that
      the action of stobadine on the respiratory and vascular smooth muscle effects is
      intermediate between that of diphenhydramine and dithiadene. In view of the
      minimal effect of stobadine on gastric acid secretion and its marked activity on
      airways, it is concluded that this drug predominantly acts on H1-receptors.

PMID- 1978645
TI  - Repeated treatment with antidepressants does not modify the locomotor effect of
      dopaminergic stimulants injected into the rat hippocampus.
AB  - In the present study, we investigated the influence of antidepressant drugs
      (imipramine, amitriptyline, citalopram, mianserin) and electroconvulsive shock on
      the locomotor effect in rats, induced by amphetamine or quinpirole injected
      intrahippocampally. The antidepressant drugs were administered in a dose of 10
      mg/kg p.o. twice daily for 14 days. Electroconvulsive shock was applied once
      daily for 10 days. Amphetamine (2.5 micrograms) or quinpirole (0.5 micrograms)
      were injected bilaterally into the hippocampus 2 or 72 hr after the last
      treatment with antidepressant drugs or electroconvulsive shock. None of the
      examined antidepressant drugs affected the response to either stimulant.
      Electroconvulsive shock potentiated the response to amphetamine but not to
      quinpirole. These results indicate that repeated treatment with antidepressant
      drugs does not modify the hippocampal dopamine system. The mechanism involved in
      the potentiation of the response to amphetamine following repeated
      electroconvulsive shock remains to be elucidated.

PMID- 1978647
TI  - Depression, depressants, and antidepressants.

PMID- 1978646
TI  - Antidotes to lethal cocaine toxicity in the rat.
AB  - Cocaine, like catecholamines or angiotensin II, may induce lethal cardiac or
      cerebral damage. Restrained rats were fitted with a caudal arterial catheter for
      on-line cardiovascular monitoring and antidote administration. They were given 60
      mg/kg of cocaine i.p., a dose which produces behavioral and cardiovascular
      effects, convulsions and death in an average time of 10 min. Selected antidotes
      were administered 5 min after the lethal dose of cocaine. Incidence of lethality
      was not changed by propranolol, prazosin, labetalol, diazepam or enalaprilat, a
      converting enzyme inhibitor. Animals treated with any one of the following
      agents, alpha- or beta-blockers, diazepam or competitive inhibitors of
      angiotensin II [Sar-1-ile-8] and [Sar-1-thr-8] angiotensin II, presented
      myocardial infarction. All animals treated with calcium channel antagonists or
      enalaprilat, whether they survived or not, did not present myocardial infarction.
      Treatment with nitrendipine, flunarizine or diltiazem, resulted in survival of
      the animals with no observable aftereffects. Similar results were observed when
      enalaprilat was administered, with diazepam as an antidote, to a lethal dose of
      cocaine. Antagonists to the sympatho-adrenal system and to the renin angiotensin
      system appear to be effective antidotes to cocaine toxicity in the present
      experimental model.

PMID- 1978648
TI  - Increased prescribing of antidepressants subsequent to beta-blocker therapy.
AB  - Using records of the Saskatchewan Prescription Drug Plan, we determined the
      incidence of antidepressant use (a marker for depressive symptoms) in patients
      who received beta-blockers or other treatments for chronic diseases (diuretics,
      antihypertensives, and hypoglycemics) during 1984, but not in the previous 6
      months. Antidepressants initiated within 12 months after the study drug were
      counted. Of the 3218 new beta-blocker users, 6.4% received concurrent
      prescriptions (ie, within 34 days) for an antidepressant and beta-blocker. Only
      2.8% of the reference group (no study drug use) received an antidepressant. A
      greater proportion of patients prescribed propranolol (9.5%) received an
      antidepressant than those prescribed other "lipophilic" (3.9%) or "hydrophilic"
      (2.5%) beta-blockers. Incidence ratios for propranolol revealed the overall risk
      antidepressant use was 4.8 (95% confidence interval [CI], 4.1 to 5.5) times that
      of the reference group and 2.1 (95% CI, 1.7 to 2.5) times that of all other study
      drug users. For propranolol, relative risk of antidepressant use (drug/reference
      group) varied with age and was greatest in the 20- to 39-year-old group (17.2;
      95% CI, 13.7 to 21.5).

PMID- 1978649
TI  - H2 receptor antagonists.

PMID- 1978650
TI  - [Betablockers, anti-arrhythmia and anti-ischemia agents and other drugs ... in
      the follow-up of myocardial infarction].

PMID- 1978651
TI  - [Cardiomyopathy in the peripartum period: current aspects. A multicenter study.
      11 cases].
AB  - Eleven of 17 case histories recensed after an inquiry addressed to all the French
      university hospital cardiological departments were attributed to peripartum
      cardiomyopathy. Three patients (27%) needed cardiac transplantation. Predisposing
      factors were multiparity and twin pregnancies. Forty five per cent of patients
      were under 25 years of age. Hypoproteinemia was present in all serious forms of
      the condition. Hypoproteinemia, a cardio-thoracic ratio of over 0.60,
      echocardiographic left ventricular fractional shortening of under 15 per cent and
      presistance of symptoms after one month of medical treatment were poor prognostic
      factors. The relatively high incidence of myocarditis (1 out of 11 cases)
      justifies endomyocardial biopsy.

PMID- 1978652
TI  - [Effects of alpha adrenergic stimulation on the mechanical properties of the
      myocardium].
AB  - The mechanical effects of phenylephrine at 2 x 10(-6) M (PE1, n = 8), 2 x 10(-5)
      M (PE2, n = 10) and 2 x 10(-4) M (PE3, n = 6) were studied on rat left
      ventricular papillary muscle, in the presence of propranolol (4 x 10(-7) M) and
      0.5 mM of (Ca2+)e. The contraction-relaxation coupling was studied under isotonic
      and isometric conditions. The maximal velocity of contraction (max Vc) and
      relaxation (max Vr) were calculated during isotonic contraction with preload only
      at L max. The positive (+ dF/dt max) and negative (- dF/dt max) peaks of the
      derivative of the force were calculated during isometric contraction. Two
      coefficients, R1 = max Vc/max Vr and R2 (+ dF/dt max)/(- dF/dt max) provided an
      appreciation of the contraction-relaxation coupling at low and high loads
      respectively. The positive inotropic effect observed in the three groups was
      accompanied by a significant decrease of the coefficient R1 (PE1: - 11 +/- 2% p
      less than 0.001; PE2: - 15 +/- 2%, p less than 0.001; PE3: -20 +/- 2%, p less
      than 0.001). On the other hand, no significant variations of the coefficient R2
      were observed (PE1: 3 +/- 3%; PE2: 1 +/- 4%; PE3: 5 +/- 3%). The proportionally
      greater improvement in the velocity of relaxation compared to the velocity of
      contraction at low loads suggests that the sarcoplasmic reticulum is involved in
      the expression of positive inotropic and positive lusitropic effects of alpha
      adrenergic stimulation.

PMID- 1978653
TI  - Gilles de la Tourette syndrome is not linked to D2-dopamine receptor.
AB  - Gilles de la Tourette syndrome has an important genetic component; the
      pathophysiology of this disorder may involve the dopamine system. We tested a D2
      dopamine receptor (locus DRD2, recognized by probe hD2G1) for genetic linkage
      with Gilles de la Tourette syndrome. Using a genetic linkage map of the region of
      DRD2 on the long arm of chromosome 11 and restriction fragment length
      polymorphism data from a total of four markers (DRD2 itself, D11S84, D11S29, and
      PBGD), we were able to exclude linkage of this candidate gene and Gilles de la
      Tourette syndrome in two extended kindreds segregating for Gilles de la Tourette
      syndrome. This rules out causation of Gilles de la Tourette syndrome by mutation
      in DRD2 in the kindreds studied under the genetic assumptions we employed; use of
      the map and multipoint linkage analyses also allowed us to exclude a Gilles de la
      Tourette syndrome susceptibility locus from a larger genetic region.

PMID- 1978654
TI  - Synthesis and structure-activity relationship of some new beta-blocking agents
      with possible alpha-adrenoreceptor activity.
AB  - A series of new phenoxypropanolamines with cyclic guanidine and isothiourea
      moieties has been prepared and investigated for non-specific beta- and alpha
      adrenoreceptor activity by receptor binding experiments on crude rat brain
      membrane. Some of them [9a, 10c] possess affinity for both beta- and alpha
      adrenoreceptors.

PMID- 1978655
TI  - [5,6-Dihydro-6-methoxy-2H-pyran-3(4H)-one, a building block for the synthesis of
      CNS agents].
AB  - The phenyl-pyranyl-piperidin derivative 5, prepared from the title compound 2,
      shows a strong stimulating effect in animals. Reactions of 2 with 2-amino
      phenylcarbonyl derivatives or phenylhydrazine can lead to [3,2-b] as well as [3,4
      b] annulated pyranes. Regioselective reactions in 2- or 4-position of 2 are
      successful after conversion to the enamine 14a, the silylenolether 24 and the
      lithioenamine 29. Cycloadditions, cyclocondensations or electrophilic
      aldoleractions yield the pyrano-pyranes 16 and 19a, resp., or the hydroxybenzyl-
      and hydroxybenzylidenpyranes 25 and 30, resp.

PMID- 1978656
TI  - The reactions of pindolol, mepindolol, carazolol, and related model compounds
      with triethyl orthoformate: pathways and products of a new colour reaction.
AB  - The acid-catalysed electrophilic tandem substitutions of pindolol, mepindolol,
      and carazolol and some related model compounds with triethyl ortho formate give
      rise to new derivatives from the trishetaryl methane series. In some cases also
      further functionalized heterocycles were isolated. The structural aspects of the
      new trishetarylmethanes were discussed as C3-symmetric molecular propellers,
      respectively. The importance of the described reaction as colour reaction was
      mentioned.

PMID- 1978657
TI  - [40th Congress of the Japanese Society of Allergology. Nagasaki, 14-16 November
      1990. Abstracts].

PMID- 1978658
TI  - [XLVI congress of the Brazilian Society of Cardiology. Curitiba, Brazil,
      September 1990. Abstracts].

PMID- 1978659
TI  - Serum type III procollagen peptides in patients with hepatointestinal and
      compensated hepatoesplenic schistosomiasis forms.
AB  - The Serum Type III Procollagen Peptides (SIIIPP) were determined in 35
      individuals: 25 untreated schistosomotics: 16 with hepatointestinal (HI) and 9
      with the compensated hepatosplenic (CHE) forms and a control group (C) consisted
      of 10 healthy volunteers. Kits of radioimmunoassay were performed for SIIIPP
      dosage. It was searched whether there was relationship between the SIIIPP and the
      serum levels of alanine aminotransferase (ALAT), aspartate aminotransferase
      (ASAT), alkaline phosphatase (AP) and gamma glutamyltranspeptidase (GGTP). The
      mean values of SIIIPP in the forms of HI (13.0 ng/ml) and CHE (17.0 ng/ml) were
      significantly higher than controls (9.0 ng/ml) (p less than 0.05). No significant
      difference was observed in SIIIP values between the HI and CHE patient groups,
      and between SIIIPP and ALAT, ASAT, AP and GGTP serum levels.

PMID- 1978662
TI  - [25th conference of the Japanese Medical Society of Alcohol Studies. Kyoto, 16-18
      October 1990. Abstracts].

PMID- 1978660
TI  - Cerebrospinal fluid as a reflector of central cholinergic and amino acid
      neurotransmitter activity in cerebellar ataxia.
AB  - Cerebrospinal fluid (CSF) amino acid neurotransmitters, related compounds, and
      their precursors, choline levels, and acetylcholinesterase activity were measured
      in the CSF of patients with cerebellar ataxia during a randomized, double-blind,
      crossover, placebo-controlled clinical trial of physostigmine salicylate. The CSF
      gamma-aminobutyric acid, methionine, and choline levels, adjusted for age, were
      significantly lower in patients with cerebellar ataxia compared with controls.
      Physostigmine selectively reduced the level of CSF isoleucine and elevated the
      levels of phosphoethanolamine. No change occurred in CSF acetylcholinesterase
      activity and in the levels of plasma amino compounds in patients with cerebellar
      ataxia when compared with controls. Median ataxia scores did not statistically
      differ between placebo and physostigmine nor did functional improvement occur in
      any of the patients.

PMID- 1978661
TI  - Long-term effect of dopaminergic drugs in restless legs. A 2-year follow-up.
AB  - Thirty patients with restless legs syndrome, who initially had all responded well
      to treatment with levodopa and benserazide, were studied as to the long-term
      effect of the drugs (at least 2 years). During the 2-year period, two patients
      were switched from levodopa to bromocriptine. Two patients no longer needed
      levodopa; one of them had developed paraplegia and in the other the symptoms of
      restless legs syndrome had disappeared completely. The remaining 26 patients
      continued to use levodopa. Eight patients maintained the original dose, nine had
      to use an increased dose, and nine found a decreased dose to be sufficient. The
      only side effect was transient nausea reported by two of the 30 patients. The
      study showed that the relief of symptoms of restless legs syndrome by
      dopaminergic drugs does not wear off with the passage of time, that side effects
      are minimal even with long-term use, and that the dose needed to obtain relief
      may increase as well as decrease.

PMID- 1978663
TI  - Unilateral cryptorchidism: an animal model.
AB  - Unilateral division of the distal gubernaculum testis was performed, using
      hypothermic anaesthesia, in Wistar rats within 48 hours of birth. This resulted
      in ipsilateral abdominal testicular retention and contralateral descent. This
      model is suitable for the experimental study of congenital unilateral
      cryptorchidism and is presented in detail.

PMID- 1978664
TI  - A survey of ECT in a general hospital psychiatry unit.
AB  - A review of the 2,256 admissions to a general hospital psychiatry unit between
      April 1982 and December 1987 showed that 129 (6%) had been treated with electro
      convulsive therapy (ECT); 91% of these had a diagnosis of mood disorder. Most
      patients were taking concurrent psychotropic medication and received an average
      of 9 treatments per course of ECT. Men and patients taking benzodiazepines had
      shorter convulsions. However, there were no differences in seizure length and
      number of treatments between younger and older patients and between those taking
      and not taking tricyclic antidepressants.

PMID- 1978665
TI  - Malaria prophylaxis and self-therapy in airline crews.
AB  - The risk of malaria infection in airline crews is estimated to be 0.5 per 1,000
      persons per night in areas with high levels of malaria transmission. Routine
      chemoprophylaxis for years is not recommended because of possible side effects.
      Airline crews should therefore use appropriate measures to prevent mosquito
      bites. In addition, they may need to carry "standby" medication with them to be
      used for presumptive treatment of a febrile illness if medical attention is not
      readily available.

PMID- 1978666
TI  - [Forensic efficiency of some highly polymorphic single locus systems].
AB  - The single locus probes MS 1, MS 8, MS 31 and MS 43 were investigated in
      combination with the restriction enzyme HINF I. The frequency distribution of
      fragment sizes detected by the polymorphic probe MS 8 was plotted for individuals
      from the Munster area and compared with an English survey. Clear discrepancies
      were found. The heterozygosity for the four systems was calculated and compared
      to the English figures. Only MS 8 showed a significant difference.

PMID- 1978667
TI  - [Flumazenil (Anexate): an antagonist of benzodiazepines. Its pharmacopsychologic
      significance and role in traffic medicine].
AB  - Flumazenil (Anexate) reverses promptly the hypnotic effects of all known
      benzodiazepines. From the point of view of traffic medicine the question is of
      interest whether side effects after application of flumazenil can be seen and
      must be taken in account. Our investigations were concerned in answering this
      question. 20 mg flumazenil or placebo was administered in a randomized
      doubleblind crossover fashion. The following psychometric tests were employed:
      Befindlichkeitsskalen von Zersen (Bf-S), State-Trait-Inventory (STAI), Hamilton
      Anxiety Scale (HAMA) und visual analogue scales (VAS). In addition, subjective
      condition was inquired. Pharmacokinetics were investigated by a radio-receptor
      assay. Flumazenil leads to an increase of negative sensations in respect to an
      invers agonizing effect. Lack of concentration and dizziness were reported by the
      probationer.

PMID- 1978668
TI  - [Applicability of the Jeffreys 33.15 and 33.6 multi-locus system].
AB  - A sample of 73 families which had been investigated by conventional paternity
      grouping was in addition subjected to DNA analysis using the multi locus systems
      33.15 and 33.6. A comparison with the results of a conventional expert's opinion
      shows complete accordance. In cases showing exclusions in the conventional
      systems there were also exclusions by the multi locus systems and in cases
      without exclusions in the conventional systems no exclusions were found using
      multi locus probes. New mutations were not observed. In stain cases the resulting
      band patterns were often partially deficient. The problems in assigning such
      patterns with those observed in fresh samples are discussed.

PMID- 1978669
TI  - Hepatic zonation of acetyl-CoA carboxylase activity.
AB  - The activities of several hepatic enzymes are preferentially zonated to the
      periportal or perivenous cells of the liver acinus. Employing dual-digitonin
      pulse perfusion of rat liver in the study of acetyl-CoA carboxylase (ACC), we
      have identified a heretofore unrecognized feature of hepatic zonation, namely an
      intrahepatic gradient in enzyme specific activity. ACC activity shows a relative
      periportal localization in normally feeding rats, even when corrected for ACC
      protein mass. In contrast with results previously reported by us [Evans,
      Quistorff & Witters (1989) Biochem. J. 259, 821-829], the total mass of both
      hepatic ACC isoenzymes was not found to differ between the two hepatic zones in
      the present study. In perfusion eluates from fed animals, periportal ACC displays
      enhanced citrate reactivity and two kinetic components of acetyl-CoA reactivity;
      the largest periportal/perivenous gradient (5-fold) is accounted for by a species
      with a lower Km for acetyl-CoA. The zonal gradient in ACC maximal velocity,
      measured in eluates from fed rats, does not persist after ACC purification,
      although the isolated periportal enzyme, like dephosphorylated ACC, has a lower
      activation constant for citrate. Total ACC protein phosphatase activity is higher
      in periportal eluates, but no differences in the activities of either a 5'-AMP
      activated ACC kinase or the cyclic-AMP-dependent protein kinase are noted between
      the hepatic zones. The induction of total hepatic ACC mass and specific activity,
      on fasting/refeeding with a high-carbohydrate diet, abolishes the
      periportal/perivenous activity gradient, largely owing to a selective activation
      of perivenous enzyme. Nutritional induction is also accompanied by a marked
      alteration in ACC acetyl-CoA kinetics and abolition of the gradient in total ACC
      phosphatase. These studies indicate that hepatic enzyme zonation, which is often
      attributed to differential expression of enzyme protein, may result from zonal
      variations in enzyme specific activity, owing to differences in allosteric
      regulation and/or covalent modification.

PMID- 1978670
TI  - Protein-serine kinase from rat epididymal adipose tissue which phosphorylates and
      activates acetyl-CoA carboxylase. Possible role in insulin action.
AB  - 1. Most of the cyclic-nucleotide-independent acetyl-CoA carboxylase kinase
      activity in an extract of rat epididymal adipose tissue was evaluated from a Mono
      Q column by 0.175 M-NaCl at pH 7.4. The activity of the kinase in this fraction
      (fraction 1) was increased after exposure of intact tissue to insulin. 2.
      Incubation of purified adipose-tissue acetyl-CoA carboxylase with [gamma-32P]ATP
      and samples of fraction 1 led to the incorporation of up to 0.4 mol of 32P/mol of
      enzyme subunit. Most of the phosphorylation was on serine residues within a
      single tryptic peptide. This peptide, on the basis of two-dimensional t.l.c.
      analysis, h.p.l.c. and Superose 12 chromatography, appeared to be the same as the
      acetyl-CoA carboxylase peptide ('I'-peptide) which exhibits increased
      phosphorylation in insulin-treated tissue. 3. Phosphorylation of purified acetyl
      CoA carboxylase by the kinase in fraction 1 was found to be associated with a
      parallel 4-fold increase in activity. However, increases in both phosphorylation
      and activity were much diminished if fraction 1 was treated by Centricon
      centrifugation to remove low-Mr components. Among these components was a potent
      inhibitor of acetyl-CoA carboxylase activity which appeared to be necessary for
      the kinase in fraction 1 to be fully active. 4. The inhibitor remains to be
      identified, but inhibition requires MgATP, although the inhibitor itself does not
      cause any phosphorylation of the carboxylase. No effects of insulin were observed
      on the activity of the inhibitor. 5. It is concluded that the kinase probably
      plays an important role in the mechanism whereby insulin brings about the well
      established increases in phosphorylation and activation of acetyl-CoA carboxylase
      in adipose tissue.

PMID- 1978671
TI  - Glutamine-synthesizing activity in lungs of fed, starved, acidotic, diabetic,
      injured and septic rats.
AB  - The maximal catalytic activity of glutamine synthetase was measured in lung
      homogenates of the rat (being 5.46 +/- 0.29 mumol/min per g wet wt. or 31.70 +/-
      2.62 nmol/min per mg of protein at 37 degrees C, in fed animals). The activity is
      similar to that of liver, but 16-fold higher than that in quadriceps muscles.
      Chronic (NH4Cl-induced) or acute (HCl-induced) metabolic acidosis had no effects
      on enzyme activity, but there was a marked increase in the activity of glutamine
      synthetase in starved (30-40%), streptozotocin-diabetic (17%), dexamethasone
      treated (18-22%), laparotomized (25-27%) and septic rats (24-45%).

PMID- 1978672
TI  - Primary structure and activity of mouse methylmalonyl-CoA mutase.
AB  - Methylmalonyl-CoA mutase (MCM) is an adenosylcobalamin-dependent enzyme that
      catalyses isomerization between methylmalonyl-CoA and succinyl-CoA (3
      carboxypropionyl-CoA). Genetic deficiency of this enzyme in man causes an often
      fatal disorder of organic acid metabolism termed mut methylmalonicacidaemia. We
      report cloning of a mouse MCM cDNA and the characterization of its primary
      structure and biological function. Mouse MCM in fibroblasts and crude liver
      extracts exhibits activity and reaction kinetics similar to those of the human
      enzyme. The predicted amino acid sequence of mouse MCM exhibits 94% identity with
      its human homologue and considerable identity with a prokaryotic MCM.
      Transfection of the mouse cDNA into cultured cells constitutes an active
      apoenzyme and can complement genetic deficiency of the apoenzyme in cells from
      patients with mut methylmalonicacidaemia. These results establish that mouse MCM
      is homologous to human MCM in structure and function and provides a basis for
      using the mouse as a model for studying this enzyme and its deficiency state.

PMID- 1978673
TI  - Possible binding site of thyrotropin binding inhibitor immunoglobulin (TBII) on
      the thyrotropin (TSH) receptor, which is different from TSH binding site.
AB  - A synthetic decapeptide, P-194, which has the sequence No. 103 to 111 of hTSH
      receptor structure with an additional N-terminal tyrosine, did not bind TSH nor
      affected its receptor binding and thyroid stimulating activity. Preincubation of
      P-194 with sera from thyroid patients caused a significant decrease in TBII
      activity in almost all 12 TBII positive sera and an increase of thyroid
      stimulating activity in 3 of 7 Graves' IgG studied. In addition, [125I] P-194
      bound to serum IgG fraction from thyroid patients with a positive correlation
      with TBII (N = 35, r = 0.509, p less than 0.01). The P-194 portion may be, at
      least a part of, TBII binding site distinct from the TSH binding site on the TSH
      receptor.

PMID- 1978674
TI  - Activation of soluble guanylate cyclase by nitrovasodilators is inhibited by
      oxidized low-density lipoprotein.
AB  - In the presence of oxidized low-density lipoprotein the stimulatory effects of
      nitric oxide, sodium nitroprusside and S-nitrosoglutathione on soluble guanylate
      cyclase partially purified from bovine platelets were diminished in a
      concentration-dependent manner with IC50 values around 100 micrograms total
      cholesterol/ml. This inhibitory effect was potentiated about 10-fold when the
      enzyme was pre-incubated with the lipoprotein for 10 minutes at 37 degrees C
      which indicates a direct interaction of the lipoprotein with the guanylate
      cyclase. As oxidized low-density lipoprotein is present in the wall of
      atherosclerotic arteries, we suggest that the impaired response of
      atherosclerotic blood vessels to vasodilators may be due to a diminished
      activation of smooth muscle guanylate cyclase.

PMID- 1978675
TI  - Metabolism of vasoactive peptides by plasma and purified renal aminopeptidase M.
AB  - Aminopeptidase M (AmM; EC 3.4.11.2) is a membrane-bound peptidase present on
      renal brush border and vascular plasma membrane. In the present study, AmM,
      purified from rabbit kidney cortex, produced a single immunoprecipitin line
      against AmM antisera, hydrolyzed alanyl-, leucyl- and arginyl-beta-naphthylamides
      at rates of 5.1 +/- 0.5, 3.9 +/- 0.5 and 2.6 +/- 0.3 mumol/min/mg, respectively,
      exhibited little or no alpha-glutamyl-, aspartyl- or glycyl-prolyl
      naphthylamidase activities (less than or equal to 0.14 mumol/min/mg), and was
      inhibited by o-phenanthroline, amastatin (IC50 = 400 nM) and bestatin (IC50 = 6
      microM). The alanyl-naphthylamidase activity of unfractionated rabbit plasma was
      found to be identical to purified AmM regarding relative rates of hydrolysis of
      alanyl-, leucyl- and arginyl-naphthylamides (100:79:42), pH optimum, and
      inhibition profile. In comparative studies with the purified enzyme,
      immunoreactive AmM accounted for essentially all of the alanyl-2-naphthylamidase
      activity of rabbit plasma. N-Terminal metabolism of (Met5)enkephalin by purified
      renal AmM was 3.92 +/- 0.69 mumol/min/mg, followed by somatostatin (1.25
      mumol/min/mg), hepta(5-11)substance P (1.14 +/- 0.13 mumol/min/mg),
      (Asn1)angiotensin II (1.11 +/- 0.06 mumol/min/mg), angiotensin III (0.45 +/- 0.04
      mumol/min/mg) and des(Asp1)-angiotensin I (0.36 +/- 0.04 mumol/min/mg). In
      contrast, substance P, bradykinin, (Sar1,Ala8)angiotensin II and neurokinin
      analogs containing modified N-termini (e.g. Ac-Arg) were resistant to hydrolysis
      by AmM. Peptide degradation was optimal at neutral pH and was inhibited by
      amastatin (IC50 = 200 nM) and bestatin (IC50 = 5 microM). Apparent Km values
      ranged from 15.7 +/- 0.4 microM for angiotensin III to 102 +/- 2 microM for
      (Met5)enkephalin. These data support a significant role for vascular and plasma
      AmM in the metabolism of circulating vasoactive peptides.

PMID- 1978676
TI  - Dimethylphenylpiperazinium (DMPP)-induced relaxation and elevation of cyclic GMP
      content in canine lower esophageal sphincter (LES).
AB  - Cyclic GMP has been proposed as an intracellular mediator of neuronally-induced
      relaxation in lower esophageal sphincter (LES) smooth muscle. If cyclic GMP is
      indeed an intracellular messenger, then agents that activate enteric neurons of
      the sphincter [e.g. the ganglionic nicotinic receptor agonist
      dimethylphenylpiperazinium (DMPP)] also should cause a relaxation that is
      associated with an increase in cyclic GMP content. In isolated smooth muscle
      strips of canine LES, DMPP produced a rapid relaxation that was accompanied by a
      significant (P less than 0.05) increase in cyclic GMP content with no change in
      cyclic AMP content. Pretreatment of tissues with either tetrodotoxin or
      hexamethonium antagonized both the DMPP-induced relaxation and the associated
      increase in cyclic GMP. The combination of phentolamine and meclofenamic acid
      also antagonized both the relaxation and the elevation of cyclic GMP produced by
      DMPP. Electrical field stimulation (EFS)-induced relaxation and elevation in
      cyclic GMP was unaltered by meclofenamic acid and phentolamine. In conclusion,
      DMPP (like neuronal electrical activation) relaxed isolated canine LES through an
      enteric neuronal inhibitory pathway. The presence of phentolamine and
      meclofenamic acid did not affect EFS-induced effects, but blocked both the
      relaxation and the increase in cyclic GMP produced by DMPP, suggesting a more
      complicated pathway for DMPP in the release of inhibitory transmitter.

PMID- 1978677
TI  - Inhibition of phospholipid methylation by an anti-allergic agent, NCO-650, during
      histamine release.
AB  - Antigen, anti-IgE and concanavalin A (Con A) induced an increase in both the
      incorporation of the 3H-methyl moiety into phospholipids and histamine release.
      Maximal incorporation of the 3H-methyl moiety into the lipid fraction of the
      cells was observed within 15 sec and 1 min after being challenged with antigen
      (100 micrograms/mL) and anti-IgE (200 micrograms/mL) respectively. However, the
      methylated phospholipid decreased rapidly. The addition of Con A (10
      micrograms/mL) also increased phospholipid methylation, which reached a maximum
      at 5 min after challenge. Trans-4-guanidinomethylcyclohexanecarboxylic acid p
      tert-butylphenyl ester hydrochloride (NCO-650; 27 microM) strongly inhibited the
      incorporation of the 3H-methyl moiety into phospholipid by antigen, anti-IgE and
      Con A. The IC50 values of NCO-650 for phospholipid methylation in response to
      antigen, anti-IgE and Con A were 1.5, 4.7 and 1.1 microM respectively. Although
      the Ca2(+)-ionophore A23187 did not induce phospholipid methylation, it caused
      histamine release.

PMID- 1978678
TI  - Effect of phenobarbital on the glucocorticoid receptor in rat hepatoma cells.
AB  - Phenobarbital is a potent inducer of several liver-specific genes such as those
      encoding detoxication enzymes, including cytochromes P450. However, the
      mechanisms of action of the barbiturate are poorly understood. Since both,
      phenobarbital and glucocorticoids, are capable of inducing the same cytochrome
      P450 species, we asked whether the glucocorticoid receptor could participate to
      the phenobarbital induced responses. The results presented here show that
      phenobarbital was able to induce a two-fold increase in the affinity of the
      glucocorticoid receptor for the binding of dexamethasone, as well as a 30%
      increase of the receptor number in Reuber rat hepatoma cells of the Fao line.
      These effects may have a biological significance since they were paralleled by an
      enhancement of the dexamethasone-induced tyrosine aminotransferase activity, a
      glucocorticoid inducible function in rat hepatoma cells and in rat liver. To our
      knowledge, phenobarbital is the first compound shown to be able to induce, in
      intact cells, an increase in the affinity of the glucocorticoid receptor for the
      binding of its ligand.

PMID- 1978679
TI  - Effect of a new alpha 2-adrenoceptor antagonist on poststenotic coronary
      resistance and myocardial function.
AB  - The effect of the alpha 2-adrenoceptor antagonist 4-fluoro-2-(imidazoline-2
      ylamino)-isoindoline maleate (BDF 8933) on poststenotic end-diastolic distal
      coronary resistance and poststenotic myocardial function (sonomicrometry) was
      investigated under control conditions and during cardiac sympathetic nerve
      stimulation (CSNS = electrical stimulation of the left ventrolateral cervical
      cardiac nerve). In 7 vagotomized, open-chest dogs end-diastolic distal coronary
      resistance was determined. This variable was essentially unchanged after
      administration of the agent. In additional 6 dogs regional myocardial function
      was measured as systolic wall thickening (SWT). CSNS increased SWT of the
      posterior circumflex-perfused myocardium from 12.7 +/- 4.6% to 21.9 +/- 8.4% (p
      less than 0.05) under control conditions. With a severe stenosis on the left
      circumflex coronary artery, SWT was reduced to 5.4 +/- 4.0% and further decreased
      to 2.1 +/- 5.1% (p less than 0.05) during CSNS. After i.v. injection of 150
      micrograms/kg BDF 8933, poststenotic myocardial function at rest was 4.2 +/-
      4.2%, and 5.6 +/- 3.6% during CSNS. Regarding to the systemic effects BDF 8933
      significantly increased peak left ventricular pressure in all 13 dogs. Thus, the
      new alpha 2-adrenoceptor antagonist BDF 8933 at the chosen dosage prevents
      sympathetically induced myocardial ischemia, but increases left ventricular
      afterload resistance.

PMID- 1978680
TI  - [Anti-ischemic action of the transdermally-applied beta-receptor blocker,
      mepindolol, in patients with stable angina pectoris. Comparison with transdermal
      nitrate].
AB  - A new transdermal beta-blocker containing system (Mepindolol BIO TSD) was
      compared in a placebo controlled cross over trial with a transdermal nitrate
      system in 14 patients suffering from coronary heart disease with stable angina
      pectoris. Under Mepindolol TSD both the incidence of angina pectoris attacks and
      the consumption of oral nitroglycerin dropped significantly. Under ergometry it
      resulted in an improvement in the maximum exercise tolerance and in a significant
      reduction in the ischemic ST-Segment deviation. Under Holter monitoring the
      number of manifest (MMI) and silent (SMI) ischemic episodes was significantly
      reduced. In addition the total duration of ischemia was significantly reduced.
      All the examined parameters showed Mepindolol BIO TSD to be significantly more
      effective than transdermal nitrate, and the duration of action was longer. No
      clinically relevant adverse events were observed in any of the therapeutic
      regimes.

PMID- 1978681
TI  - Investigations with the novel non-opioid analgesic flupirtine in regard to
      possible benzodiazepine-like abuse inducing potential.
AB  - Flupirtine (D-9998, Katadolon, CAS 56995-20-1); CAS 56995-20-1), a novel non
      opioid analgesic was investigated for possible benzodiazepine-like activities. In
      receptor binding studies flupirtine and its metabolite were found to reveal no
      affinity for specific 3H-flunitrazepam binding up to a concentration of 10
      mumol/l. In drug discrimination studies, rats were trained to discriminate the
      novel analgesic flupirtine (10 mg/kg i.p.) from no drug (NaCl 0.9%) under a two
      choice fixed-ratio 5 shock-termination schedule. Flupirtine yielded a dose
      response curve with an ED50 of 3.9 mg/kg i.p. In generalization tests with a
      benzodiazepine-type compound lorazepam (0.3 mg/kg, i.p.) did not generalize to
      the flupirtine training dose. In physical dependence studies using rats, during
      and after chronic oral administration of flupirtine (2 x 80 mg/kg p.o.) over 45
      days no signs of benzodiazepine- and opiate-like physical dependence were
      observed in rats after withdrawal of the drug. In contrast diazepam (2 x 5 bzw. 2
      x 10 mg/kg p.o.) induced typical symptoms of physical dependence. A significant
      weight loss of the codeine treated animals (2 x 60 mg/kg p.o.) and other typical
      side effects were also observed after withdrawal of codeine. These results
      clearly demonstrate that flupirtine has no affinity for benzodiazepine receptors
      and is free of benzodiazepine or opiate/opioid-like abuse potential.

PMID- 1978682
TI  - Rearrangements in the LDL receptor gene in Dutch familial hypercholesterolemic
      patients and the presence of a common 4 kb deletion.
AB  - DNA samples from 53 unrelated Dutch patients with familial hypercholesterolemia
      (FH) were screened for rearrangements in the gene for the LDL receptor (LDLR) by
      Southern analysis. Four different mutations have been detected by hybridisation
      of BglII digested genomic DNA with an exon 10-14 containing cDNA probe. The
      mutations are defined by a 7 kb insertion near exon 11, a partial gene
      duplication encompassing exons 9-12, a 4 kb deletion of exons 7 and 8 and an 0.4
      kb deletion comprising the 5'-part of exon 16. These four different
      rearrangements in the LDLR gene account for 17% of the mutations in the Dutch FH
      population sample. Interestingly, the 4 kb deletion was detected in 5 unrelated
      FH patients (9.5%) and appeared to be identical to the deletion previously
      described (Russell, D.W. et al., Arteriosclerosis, 9 (Suppl. I) (1989) I-8;
      Russell, D.W. et al., Cold Spring Harbor Symp. Quant. Biol., 51 (1987) 401). in
      an FH patient of Dutch origin. This suggests that the 4 kb deletion is a common
      mutation in the Dutch FH population.

PMID- 1978683
TI  - Lipid phenotypes, apolipoprotein genotypes and cardiovascular risk in
      nonagenarians.
AB  - Despite great interest in the role of lipids in overall and disease-free
      survival, virtually no information is available on the lipids, lipoproteins and
      apolipoproteins of persons over 90 years of age. Furthermore, the genetic
      underpinnings of atherosclerosis and the particular genetic factors responsible
      for protection against coronary artery disease remain speculative. In Bloomfield,
      Nebraska, we studied 41 nonagenarians (10 males, 31 females), with a mean age of
      92.7 years, in whom lipids, lipoproteins, apolipoproteins and restriction
      fragment length polymorphisms (RFLPs) of genes for apolipoprotein B (apo B), aop
      AI and apo CIII were assessed. Nearly complete historical, physical and
      laboratory data were obtained on 39 subjects. The mean diastolic and systolic
      blood pressures for this group were nonhypertensive, body mass indices
      (weight/height2) had a mean of 23.9 and triceps skinfold thickness measurements
      an overall mean of 14.8 mm. The mean total serum cholesterol was 5.42 mmol/l. HDL
      cholesterol levels in females persisted to be higher when compared to males (P
      less than 0.013). The allele frequencies for apo AI (MspI and PstI), apo CIII
      (Sst) and apo B (XbaI) gene RFLPs were typical for larger population studies. In
      these preliminary studies, we did not identify a distinctive phenotype, genotype,
      or phenotype-genotype relationship. Diversity of cardiovascular risk was the
      hallmark of these nonagenarians.

PMID- 1978684
TI  - Arachidonic acid-induced secretion in the rat colon. Indomethacin-resistant
      neuronal and epithelial actions.
AB  - The effect of arachidonic acid on short-circuit current (Isc) was studied in two
      preparations of the rat colon descendens, one with and one without the submucosal
      plexus. In both preparations, arachidonic acid (10(-7)-5 x 10(-5) mol.l-1)
      increased Isc concentration-dependently. The cyclooxygenase blocker,
      indomethacin, inhibited its action only partially. The lipoxygenase inhibitor,
      nordihydroguaiaretic acid, was an ineffective inhibitor of the response to
      arachidonic acid. Tetrodotoxin (TTX), atropine, and hexamethonium blocked the
      effect of arachidonic acid in the preparation with the submucosal plexus.
      Inhibition by neuronal blockers was also observed in the presence of
      indomethacin. After removal of the submucosal plexus, TTX no longer affected the
      Isc response evoked by arachidonic acid. This epithelial action of arachidonic
      acid was inhibited by the calmodulin antagonist, trifluoperazine, and the intra
      cellular Ca2(+)-antagonist, TMB-8. Inhibition by these drugs was also found in
      the presence of indomethacin. Consequently, for the secretion induced by
      arachidonic acid two sites of action, the submucosal plexus and the epithelium,
      and two mechanisms of action, prostaglandin-mediated and non-mediated, could be
      distinguished.

PMID- 1978685
TI  - CD 18 monoclonal antibody inhibits neutrophil diapedesis in the murine dermis
      induced by leukotriene B4 and 12(R)-hydroxyeicosatetraenoic acid.
AB  - Neutrophil accumulation is a hallmark of the inflammatory process. The ability of
      neutrophils to release lipid mediators, toxic oxygen metabolites, proteolytic
      enzymes and cationic proteins may contribute to the tissue pathology seen in
      inflammatory diseases such as inflammatory bowel disease and psoriasis. The first
      step in the process of neutrophil diapedesis in a gradient of chemoattraction is
      adhesion to the microvascular endothelium, a phenomenon mediated by the
      stimulated activation of the neutrophil CD11a-c/CD18 cell surface glycoprotein
      complex. We assessed the ability of a monoclonal antibody (MoAb) (hybridoma:
      SP2/0-Ag. 14XBALB/c spleen cells; isotype: murine IgG1) to CD18 that recognizes
      the beta chain of LFA1(CD11a/CD18), MAC-1(CD11b/CD18) and CD11c/CD18 to effect
      the neutrophils response to the proinflammatory chemotaxins leukotriene B4 (LTB4)
      and 12(R)-hydroxy-5,8,11,14-eicosatetraenoic acid [12(R)-HETE] in the mouse
      dermis. LTB4 and 12(R)-HETE induce a time and concentration dependent
      infiltration of s when applied intradermally. LTB4 (100 ng) and 12(R)-HETE (50
      micrograms) were injected intradermally in CD-mice (18 g body weight) and
      assessed for chemotactic activity four h later by the dermal levels of
      myeloperoxidase (MPO), a neutrophil marker enzyme. CD18 MoAb(0.02 mg) was given
      intravenously 10 min ahead of dermal chemotaxin injection. LTB4 increased (p less
      than .01) dermal levels of MPO at 4 h, a neutrophil accumulation inhibited (p
      less than .005) by CD18 MoAb pretreatment (Mean MPO +/- SEM: Vehicle, 0.049 +/-
      0.006U vs LTB4, 0.309 +/- 0.033U vs MoAb, 0.137 +/- 0.012U) (n =
      12/group).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1978686
TI  - [Study on Ha-ras RFLPs in gastric carcinoma and normal tissue DNAs of Chinese
      individuals].
AB  - By using recombinant plasmid PHS-49 as a probe, BamHI restriction fragment length
      polymorphisms (RFLPs) was studied in tumour DNAs of 36 gastric carcinoma patients
      and normal tissue DNAs of 25 unaffected Chinese individuals. Ten alleles and
      eighteen genotypes for Ha-ras gene were found. Four "rare" restriction fragments
      of size less than 6 kilobase pairs (kb) are first reported for Ha-ras locus in
      present paper, we inferred that these alleles might be one of the characteristics
      of genetic polymorphisms in Chinese population. Moreover, the frequency of some
      "rare" alleles and genotypes occurred in gastric carcinoma samples is
      significantly higher than that occurred in normal individuals. The results of
      pedigree analysis for two patients showed that some heterozygotes carried three
      or four alleles. It suggested that there may be more than one copy of Ha-ras gene
      sequence existed in a chromosome. The possible causes of the phenomenon mentioned
      above were discussed.

PMID- 1978687
TI  - A restriction fragment length polymorphism for human topoisomerase II: possible
      relationship to drug-resistance.
AB  - In previous studies we used Southern blotting to examine the topoisomerase II
      locus (on chromosome 17) in human leukemia cell lines and noted a difference in
      the XmnI restriction endonuclease digestion pattern between an m-AMSA-resistant
      line and its m-AMSA-sensitive parent line (Zwelling, L. A.; Hinds, M,; Chan, D.;
      Mayes, J.; Sie, K. L.; Parker, E.; Silberman, L.; Radcliffe, A.; Beran, M.;
      Blick, M. Characterization of an amsacrine-resistant line of human leukemia
      cells. Evidence for a drug-resistant form of topoisomerase II. Journal of
      Biological Chemistry 264:16411-16420; 1989). We now demonstrate that the variable
      XmnI digestion pattern represents a normal restriction fragment length
      polymorphism (RFLP) which is observed in subjects without malignant disease and
      exhibits an autosomal pattern of inheritance. These data suggest that the
      previously described deviation in the genomic structure of topoisomerase II in
      the m-AMSA-resistant cell line did not reflect a new mutation, but rather a
      reduction to homozygosity at the topoisomerase II locus. This reduction to
      homozygosity is not due to chromosomal loss, as chromosome 17-specific gene
      probes clearly identify two chromosome 17's in the sensitive line and four in the
      resistant line, using chromosome painting with a chromosome 17-specific library.
      Some other genetic change must be the cause of the resistance of HL-60/AMSA and
      its topoisomerase II to the inhibiting actions of m-AMSA.

PMID- 1978688
TI  - Theory and practice.

PMID- 1978689
TI  - Tryptophan treatment of aggressive psychiatric inpatients.
AB  - This double-blind, placebo-controlled study tested the effectiveness of
      tryptophan (TRP) in the treatment of aggressive psychiatric inpatients. After a
      baseline observation period of 1 month, patients were randomly assigned to
      treatment either with TRP (up to 6 g/day) or with placebo. There were 10 subjects
      in each treatment group. These treatments were administered for 25-35 days, after
      which the patients were observed for 1 month. Throughout this study, patients
      were receiving other medications. Injections of antipsychotics and sedatives were
      administered as needed to control agitated or violent behavior. Blood levels of
      TRP and other large neutral amino acids were obtained repeatedly, and ratios
      between TRP and other amino acids were computed. These analyses confirmed
      significant increases of TRP ratios in TRP-treated patients. TRP treatment had no
      effect on the number of violent incidents, but it significantly reduced the need
      for injections of antipsychotics and sedatives. The study thus provided indirect
      support for beneficial effects of TRP in aggressive psychiatric inpatients.

PMID- 1978690
TI  - Maternal genomic neutrophil FcRIII deficiency leading to neonatal isoimmune
      neutropenia.
AB  - The healthy mother of a child with transient immune neutropenia was found to be
      "NA-null." The mother's neutrophils did not react with anti-NA1 and anti-NA2
      antibodies (polyclonal human alloantibodies and mouse monoclonal antibodies). A
      healthy donor was discovered during routine neutrophil antigen typing whose
      neutrophils were also "NA-null." This NA-phenotype was due to the absence of
      FcRIII (CD16 antigen) on neutrophils as demonstrated with anti-FcRIII monoclonal
      antibodies. The neutrophils of these two individuals were not able to bind
      dimeric immunoglobulin G. However, their cells had a normal expression of other
      phosphatidylinositol (PI)-linked membrane glycoprotein (CD24, CD67, and CLB
      gran/5 antigens), ruling out the existence of a PI-linkage defect, such as
      paroxysmal nocturnal hemoglobinuria. The mother (propsitus) had isoantibodies in
      her blood against neutrophil-FcRIII without allospecificity, apparently produced
      during pregnancy and responsible for the neutropenia of her child. The expression
      of FcRIII on natural killer lymphocytes of both individuals was normal. FcRIII is
      encoded by two separate genes, one (FcRIII-1) for the neutrophil-PI-linked
      receptor, another (FcRIII-2) for the natural killer cell and macrophage
      transmembrane receptor. By messenger RNA and DNA analysis (with an FcRIII-cDNA
      probe and restriction endonucleases) the neutrophil-FcRIII deficiency appeared to
      be due to deletion of the FcRIII-1 gene in both individuals, while the FcRIII-2
      gene was normally present. The parents of the propositus were found to be
      heterozygous for this defect. Thus, FcRIII-1 gene deficiency of the mother may be
      a cause of (iso)immune neutropenia of the newborn. Whether this deficiency may
      have other clinical consequences has to be studied.

PMID- 1978691
TI  - Expression of P-glycoprotein in adult T-cell leukemia cells.
AB  - We have examined the expression of P-glycoprotein (P-gp) in adult T-cell leukemia
      (ATL) samples from 25 patients. Based on immunoblotting with a monoclonal
      antibody against P-gp, C219, 8 of 20 ATL patients were P-gp positive at the
      initial presentation. All 6 patients at the relapsed stage were P-gp positive,
      and refractory to chemotherapy. The expression of MDR1 mRNA in P-gp-positive ATL
      cells was increased at the relapsed stage of one patient. P-gp of this patient
      was photolabeled with [3H]azidopine and the labeling was inhibited with
      nimodipine, vinblastine and progesterone. These results suggest that P-gp
      expressed in ATL cells from patients at relapsed stage has the same binding
      site(s) for the drugs as that in multidrug resistant cells, and is correlated
      with the refractory nature of the cells to chemotherapy.

PMID- 1978692
TI  - Receptor regulation of atrial natriuretic factor.
AB  - Two atrial natriuretic factor (ANF) receptor subtypes are present in vascular
      smooth muscle cells: the B receptors (or biologically active) coupled to a
      guanylate cyclase and the C receptors (clearance) representing 95% of the total
      number of ANF binding sites but noncoupled to a guanylate cyclase. Using binding
      experiments with 125I-ANF and measurement of cGMP production stimulated by ANF,
      we were able to demonstrate that ANF receptors are sensitive to homologous
      (induced by ANF) and heterologous regulation (induced by angiotensin II, AII) in
      rat cultured vascular smooth muscle cells. The effect of the two hormones showed
      marked differences, in their time course, their reversibility and their
      consequence on guanylate cyclase activity. Although both ANF and AII reduced the
      total number of ANF binding sites after 18 h, ANF induced a desensitization of
      the guanylate cyclase whereas AII elicited a potentialization of this system.
      From these results, we have concluded that in vascular cells B receptors are
      sensitive to homologous regulation and C receptors are sensitive to heterologous
      regulation by AII. This also highlights a specific interaction between ANF and
      AII at the receptor level.

PMID- 1978693
TI  - The first Robert Furchgott lecture: from endothelium-dependent relaxation to the
      L-arginine:NO pathway.
AB  - Nitric oxide (NO) is released from vascular endothelial cells and fresh vascular
      tissue in amounts sufficient to account for the biological actions of endothelium
      derived relaxing factor. It is synthesized from the terminal guanidino nitrogen
      atom(s) of L-arginine, a process that is inhibited by NG-monomethyl-L-arginine (L
      NMMA). Studies using L-NMMA have shown that NO is constantly generated by the
      vessel wall to maintain vasodilator tone. The L-arginine:NO pathway has now been
      identified in a number of other cells and tissues, in many of which it acts as
      the transduction mechanism for stimulation of the soluble guanylate cyclase.

PMID- 1978694
TI  - Nonpeptide angiotensin II receptor antagonists: a novel class of antihypertensive
      agents.
AB  - The most direct approach to block the function of the renin-angiotensin system
      would be to antagonize angiotensin II (AII) at the level of its receptor.
      However, the AII receptor antagonists currently available, such as saralasin, are
      peptides which still retain agonistic activity and lack oral bioavailability. We
      have identified the N-benzylimidazoles, S-8307 and S-8308, as weak, but selective
      nonpeptide AII receptor antagonists. These initial leads were subsequently
      converted into more potent compounds, such as EXP6155, EXP6803 and EXP7711, while
      maintaining the selectivity. The compounds displace 3H-AII from its specific
      binding sites in adrenal cortical membranes and smooth muscle cells. They
      competitively inhibit the vasoconstrictor response to AII in various in vivo and
      in vitro preparations, but do not influence those to KCl, norepinephrine, and
      vasopressin. Converting enzyme and renin are not affected by these agents. In
      renal hypertensive rats and sodium-depleted dogs our compounds cause a sustained
      decrease in arterial pressure following intravenous and oral (EXP7711)
      administration, and are devoid of agonistic properties. Taken together, these
      nonpeptide structures are true competitive AII receptor antagonists and represent
      a new class of effective antihypertensive agents.

PMID- 1978695
TI  - Endothelium-dependent effects of beta-adrenergic blockers.
AB  - Nonselective beta-adrenergic blockers have been reported to affect endothelium
      dependent responses in isolated blood vessels in the following ways: (a) cause
      endothelium-augmented direct relaxations; (b) facilitate the endothelium
      dependent relaxations evoked by alpha 2-adrenergic activation, or by
      acetylcholine; (c) augment the intraluminal release of vasodilator prostanoids,
      and (d) inhibit endothelium-dependent contractions to anoxia. Important species
      differences exist in terms of the endothelium-dependent effects of the compounds.
      If they were to occur in the intact organism, the endothelium-dependent effects
      of the beta-adrenergic blockers could help to explain their vasodilator
      properties.

PMID- 1978696
TI  - Mechanisms of vasodilation. Proceedings of the 5th international symposium,
      Strasbourg, France, July 5-7, 1989.

PMID- 1978697
TI  - Acid suppression: how much is needed?

PMID- 1978698
TI  - Functional characteristics of the intercellular adhesion molecule-1 (CD54)
      expressed on cytotoxic human blood lymphocytes.
AB  - We have shown that intercellular adhesion molecule-1 (ICAM-1) (CD54) positive
      cells are mainly responsible for the natural cytotoxic function of human blood
      lymphocytes. The evidences were the inhibition of cytotoxicity by anti-ICAM-1 (LB
      2) monoclonal antibodies (mAb) and the loss of lytic activity after removal of
      the ICAM-1+ cells. In addition, the cytotoxic potential of the separated ICAM-1-
      lymphocyte population after activation appeared in parallel with the expression
      of this molecule. The ICAM-1+ lymphocytes lysed both LFA-1 (CD11a/CD18 or Leu
      CAMa) positive and negative cell lines, and pretreatment of the effectors with
      the LB-2 mAb also inhibited the lysis of LFA-1- targets. The results point to a
      yet unrecognized role of ICAM-1 on the lymphocytes. Kinetics experiments
      suggested that pretreatment of lymphocytes with alpha-ICAM-1 (LB-2) mAb did not
      inhibit the promptly established lytic interactions but influenced later events,
      recycling and/or recruitment of effectors. It is possible that the cytotoxic
      potential is regulated by contacts between the members of the lymphocyte
      population and that these events occur via their ICAM-1 and LFA-1. Exposure of
      lymphocytes to NK-sensitive targets for 16 hr elevated their cytotoxic potential.
      The function of activated lymphocytes was not inhibited by the LB-2 mAb.

PMID- 1978699
TI  - Macrophages within the granulomas of murine Schistosoma mansoni are a source of a
      somatostatin 1-14-like molecule.
AB  - Inflammatory cells secrete some neuropeptides that function as immunomodulators.
      Somatostatin has immunoregulatory properties. It is unknown whether immune cells
      make somatostatin. Intricate intercellular communications govern the granulomas
      of murine Schistosoma mansoni. These granulomas synthesize several neuropeptides.
      Thus, it was determined whether somatostatin is in these inflammatory lesions.
      Granulomas, which were isolated from the livers of infected mice, contained
      somatostatin 1-14 as shown by radioimmunoassay and chromatography. Immunostaining
      localized immunoreactive somatostatin and pre-prosomatostatin to granuloma
      macrophages. Granuloma macrophages cultured in vitro released immunoreactive
      somatostatin. Calcium ionophore A23187, which promotes macrophage secretion,
      increased somatostatin in the culture supernatants. Thus, the granulomas have a
      molecule with somatostatin 1-14-like properties that is possibly a secretory
      product of the granuloma macrophage.

PMID- 1978700
TI  - Sympathetic nervous system-dependent vasoconstriction in humans. Evidence for
      mechanistic role of endogenous purine compounds.
AB  - Purine compounds modulate sympathetic neurotransmission; this modulation
      decreases nervous discharge by stimulating presynaptic inhibitory adenosine
      receptors, an effect antagonized by theophylline, and causes vasoconstriction
      through the stimulation of postsynaptic ATP receptors. In humans we evaluated the
      effect of local theophylline, which was infused into the brachial artery at the
      rate of 100 micrograms/100 cc/min, on the arteriolar sympathetic vasoconstriction
      induced by applying a lower-body negative pressure. Forearm blood flow changes
      were measured by strain-gauge venous plethysmography. Theophylline, which at this
      dosage blunted the vasodilator effect of adenosine (the physiological agonist for
      the P1 purinoceptor), significantly increased lower-body negative pressure
      mediated vasoconstriction. To evaluate whether neurotransmitters different from
      norepinephrine participate in the vasoconstrictor effect of theophylline, we
      repeated the previous experiment in the presence of phenoxybenzamine, which was
      infused at a dose (60 micrograms/100 cc/min) that abolished the vasoconstrictor
      effect of norepinephrine. Also, after alpha-adrenoceptor blockade, theophylline
      continued to increase sympathetic vasoconstriction. Our data confirm that
      purinergic receptors and neurotransmitters also participate in endogenous
      sympathetic vasoconstriction in humans.

PMID- 1978701
TI  - The specificity of anti-neutrophil cytoplasm autoantibodies in systemic
      vasculitides.
AB  - Autoantibodies to neutrophil cytoplasmic antigens are found in patients with
      small or medium-size vessel systemic vasculitis such as Wegener's granulomatosis
      and microscopic polyarteritis. We studied the specificity of anti-neutrophil
      cytoplasm autoantibodies (ANCA) by examining the binding of sera from patients
      with different forms of systemic vasculitis, to neutrophil extract size
      fractionated by gel filtration for high performance liquid chromatography.
      Sequential fractions were collected for solid-phase radioimmunoassay. Patients
      with Wegener's granulomatosis showed two peaks of activity over fractions of 12
      and 2 kD. Patients with microscopic polyarteritis had two different peaks of
      activity over fractions of 100 and 25 kD. Patients with Takayasu's arteritis and
      dermal lymphocytic vasculitis were studied as controls (all were ANCA negative by
      indirect immunofluorescence studies and solid-phase radioimmunoassay). However,
      the patient with lymphocytic vasculitis showed a distinct peak of activity over
      22 kD and patients with Takayasu's arteritis had a single peak of activity over
      200 kD. These results suggest the binding pattern of sera to fractionated
      neutrophil extract could be useful in differentiating between different diseases
      within the spectrum of systemic vasculitis. Cryptic antigen recognition in
      certain vasculitides may only be revealed by this procedure. We conclude that the
      association of ANCA and systemic vasculitis may not be limited to diseases of
      small or medium-size vessels, but could also include large vessel disease such as
      Takayasu's arteritis.

PMID- 1978702
TI  - Diverse target antigens recognized by circulating antibodies in anti-neutrophil
      cytoplasm antibody-associated renal vasculitides.
AB  - Antibodies that are directed against cytoplasmic constituents of neutrophils and
      monocytes (anti-neutrophil cytoplasm antibodies, ANCA) have been described in
      Wegener's granulomatosis, microscopic polyarteritis (MPA) and some cases of
      segmental necrotizing glomerulonephritis (SNGN). Other antibodies occasionally
      described in Wegener's granulomatosis and MPA include anti-nuclear antibodies
      (ANA) and anti-glomerular basement membrane (GBM) antibodies. We have studied the
      diversity of the corresponding antigens in ANCA-associated renal diseases. Sera
      from 46 patients with active histologically proven Wegener's granulomatosis, MPA
      and SNGN were tested for ANCA by indirect immunofluorescent examination of normal
      peripheral blood neutrophils. Thirty-four sera (74%) were positive; 16 were
      associated with diffuse cytoplasmic staining (cANCA) and 18 with perinuclear
      staining (pANCA). In addition, five demonstrated antineutrophil-specific nuclear
      staining (ANNA). On Western blotting of the neutrophil extract, five sera
      recognized a 29-kD molecule recently identified as neutrophil proteinase 3. Two
      sera with typical cANCA bound to molecules of 36, 38 and 116 kD and another to a
      molecule of 22 kD. The final serum associated with pANCA bound to a molecule of
      about 12 kD. Thirteen sera out of 46 (28%) tested in an ELISA contained anti
      myeloperoxidase antibodies; 10 of these were associated with pANCA and two others
      with ANNA. Three sera of 17 (18%) tested contained anti-elastase antibodies;
      these also contained anti-myeloperoxidase antibodies and were associated with
      pANCA. However, eight sera with pANCA were negative for anti-myeloperoxidase
      antibodies and three of these were also negative for anti-elastase antibodies,
      suggesting further unidentified target antigen or antigens associated with the
      pANCA. Fifteen of the 34 sera positive for ANCA also demonstrated anti-nuclear
      staining on Hep-2 cells (53%) in a speckled, homogeneous, or nucleolar pattern.
      ANA were significantly associated with the presence of pANCA (P less than 0.01),
      and levels of ANA and ANCA fell in parallel after treatment. One serum with a
      pANCA was also positive for anti-GBM antibodies. Inhibition studies using ELISAs
      for anti-GBM antibodies indicated that there was no cross-reactivity between
      target molecules recognized by these antibodies. The diversity of target
      molecules recognized by ANCA suggests that cross-reactivity with bacterial
      structures is less likely as the primary aetiological event in the development of
      these antibodies than tissue destruction; and that cross-reactivity with vascular
      endothelium is also unlikely as the pathogenetic basis of vessel disease.

PMID- 1978703
TI  - Titration of antibodies against neutrophil cytoplasmic antigens is useful in
      monitoring disease activity in systemic vasculitides.
AB  - Titration of antibodies against neutrophil cytoplasmic antigens (cANCA), as
      detected by indirect immunofluorescence, is shown to be clinically useful for
      monitoring disease activity in Wegener's granulomatosis and microscopic
      polyarteritis. Ten patients were followed (eight from presentation) prospectively
      for up to 2 years; during this time there were six episodes of vasculitic relapse
      in four patients and five infective episodes and one pulmonary embolus in four
      patients. Titres of cANCA were markedly raised, both at presentation (1/32
      1/2048) and at vasculitic relapse (1/125-1/1048) but not in infection or embolism
      (negative, 1/16). Thus the titre of these antibodies can distinguish
      nonvasculitic illness from vasculitic relapse, in contrast to C-reactive protein
      levels which were raised in both. Titres of cANCA fell gradually after vasculitic
      relapse, in keeping with the half-life of IgG (3 weeks). C-reactive protein is a
      better measure of recovery.

PMID- 1978705
TI  - Pulmonary artery involvement in aorto-arteritis. An analysis of DSA.
AB  - Angiographic features of the pulmonary artery were studied in 24 patients with
      aortoarteritis (Takayasu's arteritis) by digital subtraction angiography. The
      pulmonary artery involvement was found in nine cases (37.5%). The right side was
      involved in eight and the left side in five cases. The right pulmonary artery was
      involved in two cases, the lobar artery in six, the segmental artery in six, and
      subsegmental as well as peripheral branches in four. The angiographic features
      were stenosis and/or occlusion as were the changes of the systemic arteries in
      aorto-arteritis. The aorta and its main branches were involved in all nine
      patients, but the severity of pulmonary vascular changes was not always related
      to the systemic vascular changes. Bronchial angiography demonstrated enlarged and
      tortuous bronchial arteries in four cases. Lung ECT revealed abnormalities in
      four cases.

PMID- 1978704
TI  - Bacteroides gingivalis-specific serum IgG and IgA subclass antibodies in
      periodontal diseases.
AB  - The level of serum IgM, IgG and IgA antibodies including IgG1, IgG2, IgG3, IgG4,
      IgA1 and IgA2 subclass-specific antibodies to Bacteroides (Porphyromonas)
      gingivalis fimbriae and to lipopolysaccharide (LPS) were analysed in patients
      with different forms of periodontal disease (PD) and control subjects by ELISA.
      Among PD subjects, sera obtained from adult periodontitis (AP), rapidly
      progressive periodontitis (RPP) and gingivitis contained high titres of fimbriae
      specific IgG antibodies (7500-15,000 ELISA units) followed by IgA (90-700 units)
      and IgM (30-90 units). In contrast, sera from localized juvenile periodontitis
      (LJP) subjects exhibited much lower titres of fimbriae-specific IgG (89 +/- 11
      units), IgA (31 +/- 5 units) and IgM (17 +/- 3 units) antibodies. A similar
      response pattern was also seen in sera from normal subjects aged 35-41 years who
      practice normal oral hygiene, while sera of younger adults (aged 18-24) with
      superior hygiene did not have any antigen-specific antibodies. Analysis of IgG
      subclass anti-fimbriae responses revealed that the major response was IgG3
      followed by IgG1, IgG2 and IgG4 in AP, RPP and gingivitis. Although lower, a
      similar pattern of IgG subclass titre was seen in LJP and normal subjects aged 35
      41 years. When IgA subclass responses were measured in AP and RPP, higher titres
      of the fimbriae-specific response were noted with IgA1 when compared with IgA2.
      However, lower but approximately equal levels of fimbriae-specific IgA1 and IgA2
      titres were seen in other PD groups. When anti-B. gingivalis LPS-specific
      responses were measured, the sera of AP patients contained high levels of IgG
      antibodies (2265 +/- 224 units) followed by IgA (411 +/- 90 units) and IgM (214
      +/- 56 units). Further, IgG anti-LPS responses were mainly IgG2 followed by IgG4,
      IgG3 and IgG1. For IgA subclass responses, higher titres of anti-LPS-specific
      antibodies were noted in IgA2 subclass over IgA1. These results showed that
      higher anti-B. gingivalis antibody responses occur in PD when compared with
      healthy individuals and protein and lipid-carbohydrate antigens of B. gingivalis
      induce distinct patterns of antigen-specific IgG and IgA subclass responses.

PMID- 1978706
TI  - [Preliminary study on the cellular immune abnormality in rheumatoid arthritis].
AB  - The cellular immunological abnormalities in 21 patients with rheumatoid arthritis
      (RA) were studied with flow cytometer. In the peripheral blood monocytes (PBM)
      from patients with active RA the number of HLA-DR positive cells were remarkably
      increased. The activity of NK cells and Leull C+ cells reduced to 1/2-1/3 of the
      normal limits. The AMLR and mitogen-inducing reaction decreased significantly.
      These data suggest that the changes of cellular immune reaction and
      immunoregulation may be related to the pathogensis of RA.

PMID- 1978707
TI  - Identification of metabolites of 3,4-methylenedioxymethamphetamine in rats.
AB  - Liquid chromatography with electrochemical detection (LC/ECD) and gas
      chromatography/mass spectrometry (GC/MS) were used to identify metabolites of N
      methyl-3,4-methylenedioxyamphetamine (MDMA) in samples of rat plasma and urine.
      Several potential metabolites, based on what is known about the metabolism of the
      desmethyl analog (i.e., MDA), were synthesized as standards to aid in the
      identification of the MDMA metabolites. MDA and N-methyl-1-(4-hydroxy-3-methoxy
      phenyl)-2-aminopropane (3b) were identified in urine by HPLC and confirmed by
      GC/MS. 1-(4-Hydroxy-3-methyoxyphenyl)2-aminopropane, (3a), N-methyl-1-(3-hydroxy
      4-methoxyphenyl)-2-aminopropane (2b) and 1-(3,4-dihydroxyphenyl)-2-aminopropane
      (4a) were tentatively identified by LC/ECD but insufficient sample size precluded
      confirmation by mass spectrometry. MDA was also identified in brain and plasma
      extracts. Because MDA is a metabolite of MDMA in humans, and because it has been
      speculated that the neurotoxic effects of MDA and MDMA may be due to a
      metabolite, the results of the present study may ultimately aid our understanding
      of the neurotoxic mechanism of these drugs of abuse.

PMID- 1978708
TI  - Induction of antibody synthesis by CD4+ T cells: IL 5 is essential for induction
      of antigen-specific antibody responses by TH2 but not TH1 clones.
AB  - Murine B cells stimulated with lipopolysaccharide (LPS) and interleukin (IL) 4
      produce IgG1 and IgE, but synthesize IgG2a when stimulated with LPS and
      interferon-gamma. The cytokines, however, that regulate immunoglobulin (Ig)
      synthesis induced in normal B cells under antigen-driven major histocompatibility
      complex (MHC)-restricted conditions in the absence of potent B cell mitogens have
      not been fully elucidated. We and others have shown that under cognate MHC
      restricted conditions, CD4+ T cell clones of the TH1 subset, which produce IL 2
      and interferon-gamma, and T cell clones of the TH2 subset, which produce IL 4 and
      IL 5, are both capable of inducing anti-trinitrophenyl IgG plaque-forming cells.
      In this report we have examined in further detail the cytokine requirements for
      the induction of Ig synthesis in B cells cultured directly with TH1 and TH2 T
      cell clones. Using (a) TH2 clones that varied in the amount of IL 5 secreted, (b)
      a neutralizing monoclonal antibody against IL 5 and (c) T cell clones pretreated
      with cyclosporin A to inhibit cytokine secretion, we found that IL 5 was
      essential for induction of IgG1 synthesis by TH2 but not TH1 T cells. Although we
      demonstrated that IL 2 could actually up-regulate the synthesis of IL 5 by TH2
      clones, the induction of IgG synthesis by TH2 clones was entirely independent of
      IL 2. In contrast, induction of IgG1 synthesis by TH1 clones was absolutely
      dependent upon the presence of IL 2 and was not affected by the presence of IL 5.
      Thus, these studies demonstrate the idea that at least two independent pathways
      exist for the induction of IgG1 synthesis, and that one of these pathways is IL
      4/IL 5 dependent and the other IL 2 dependent.

PMID- 1978709
TI  - Molecular associations on the T cell surface correlate with immunological memory.
AB  - Different isoforms of CD45 are expressed on naive and memory CD4 T cells in the
      mouse, as revealed by an antibody to a set of isoforms of CD45 that utilize exon
      B, called CD45RB. Cloned TH1 and TH2 lines also differ for expression of isoforms
      detected by this antibody. Differential expression of CD45 isoforms correlates
      with different behavior of cell surface molecules involved in transmembrane
      signal transduction. On naive T cells, CD4, CD45 and the CD3/T cell receptor
      complex behave as independent entities. On memory T cells, these three molecules
      are stably associated on the T cell surface. Furthermore, on TH2 cells, which
      express intermediate levels of CD45RB, CD4 is stably associated with CD45
      isoforms other than CD45RB, but this complex is not associated with the CD3/T
      cell receptor. These results lead us to propose that immunological memory in CD4
      T cells consists of an altered structure of the T cell's specific signal
      transduction apparatus controlled by low-molecular weight CD45 isoforms. This
      altered receptor structure would allow the more sensitive triggering of the T
      cell characteristic of memory cells. The organization of multimolecular signal
      transduction systems may be a general means by which cells alter their
      physiological behavior, allowing the acquisition of new phenotypic
      characteristics.

PMID- 1978710
TI  - Differential responsiveness to CD3-Ti vs. CD2-dependent activation of human
      intestinal T lymphocytes.
AB  - Human lamina propria lymphocytes were recovered from surgical specimens of
      unaffected large bowel and compared with peripheral blood lymphocytes (PBL) from
      the same individual. We investigated their capacities to respond to triggering
      stimuli delivered by mitogenic monoclonal antibodies directed at the T cell
      receptor/CD3 complex or, alternatively, the CD2 glycoprotein. In marked contrast
      to PBL, expression of the interleukin 2/interleukin 2 receptor system was
      markedly reduced in LPL following activation through the CD3/T cell receptor.
      Perhaps, more important, responses to CD2 triggering were similar or even
      stronger in LPL as opposed to PBL. This indicates that the CD2-dependent
      alternative pathway of T cell activation might serve a functional role in local
      immunity in the gut.

PMID- 1978711
TI  - Porcine gamma/delta T lymphocyte subsets differing in their propensity to home to
      lymphoid tissue.
AB  - Three types of T cell receptors (TcR) gamma/delta were identified in swine, all
      of which are disulfide-bonded cell surface heterodimers. The first, a 38/40-kDa
      molecule, is related to the TcR gamma/delta of sheep and cattle, and defines in
      swine a subset of CD4-CD8- T lymphocytes that is enriched in the circulating T
      lymphocyte pool. The other two receptors are private to swine. The second, a
      37/40-kDa molecule, is expressed by the major subset of CD2-CD4-CD8- T
      lymphocytes that is neither enriched in nor excluded from lymphoid tissue. By
      contrast, the third type of TcR gamma/delta, a 40/46-kDa molecule, is found on
      CD2+CD4-CD8- T lymphocytes accumulating in lymphoid tissue. Thus, TcR gamma/delta
      T lymphocyte subsets differing in homing propensity are typified by the
      expression of distinct molecular forms of the TcR gamma/delta.

PMID- 1978712
TI  - Growth hormone, somatostatin and psoriasis.

PMID- 1978713
TI  - T-cell receptor genes in tassel-eared squirrels (Sciurus aberti). I. Genetic
      polymorphism and divergence in the Abert and Kaibab subspecies.
AB  - The role of environmental factors in the evolution and maintenance of diversity
      of antigen receptor gene families which participate in the immune response in
      mammals is inadequately understood. In order to elucidate the impact of these
      factors, we have undertaken the analysis of these gene families in the tassel
      eared squirrel (Sciurus aberti) which has been separated into discrete subspecies
      by geographic barriers and whose food resources can be quantitated for estimating
      environmental quality. In this communication we describe the initial analysis of
      the complexity and polymorphism of sequences related to T-cell receptor (Tcr)
      alpha and beta chain genes in two subspecies, Sciurus aberti aberti (Abert) and
      Sciurus aberti kaibabensis (Kaibab) which have identical habitats and are
      separated by the Grand Canyon in Arizona, USA. Genomic blot analysis of 60 Abert
      and 62 Kaibab individuals collected over a 3-year period was performed with mouse
      Tcrb and Tcra cDNA probes. Sequences homologous to Tcrb-C, Tcrb-J1, and Tcrb-J2
      genes were observed in all individuals from both subspecies; although Tcrb-J1
      fragments were monomorphic. Tcrb-C and Tcrb-J2 fragments were polymorphic with
      both species- and subspecies-specific sequences. A single, monomorphic Tcra-C
      fragment was observed in addition to multiple Tcra-V fragments homologous to the
      mouse Tcra-V1 subfamily. Abert samples exhibited greater numbers of Tcra-V1
      fragments as well as greater polymorphism than Kaibab samples. Heterozygosity
      estimates of Tcrb-C and Tcra-V1 sequences were determined for annually collected
      samples and compared with the yearly estimates of availability of hypogeous
      fungi, one of the major diet items of tassel-eared squirrels. In the Kaibab
      annual collections, Tcra-V1 heterozygosity declined with the decline in food
      resource, whereas heterozygosity of Tcrb-C sequences was inversely related to
      food resource. Similarly, a reduction in food resource for Abert squirrels in
      1985 coincided with an increase in Tcrb-C heterozygosity in the same year. These
      results suggest that the diversity of gene families which participate in the
      immune response in mammals may be affected by environmental factors.

PMID- 1978714
TI  - The chimpanzee major histocompatibility complex class II DR subregion contains an
      unexpectedly high number of beta-chain genes.
AB  - The major histocompatibility complex (MHC) class II DR subregion of the
      chimpanzee was studied by restriction fragment length polymorphism (RFLP)
      analysis. Genomic DNA obtained from a panel of 94 chimpanzees was digested with
      the restriction enzyme Taq I and hybridized with an HLA-DR beta probe specific
      for the 3' untranslated (UT) region. Such a screening revealed the existence of
      14 distinct DRB/Taq I gene-associated fragments allowing the definition of 11
      haplotypes. Segregation studies proved that the number of chimpanzee class II
      DRB/Taq I fragments is not constant and varies from three to six depending on the
      haplotype. Comparison of these data with a human reference panel manifested that
      some MHC DRB/Taq I fragments are shared by man and chimpanzee. Moreover, the
      number of HLA-DRB/Taq I gene-associated fragments detected in a panel of
      homozygous typing cells varies from one to three and corresponds with the number
      of HLA-DRB genes present for most haplotypes. However, a discrepancy is observed
      for the HLA-DR4, -DR7, and -DR9 haplotypes since a fourth HLA-DRB pseudogene
      present within these haplotypes lacks its 3' UT region and thus is not detected
      with the probe used. These results suggest that chimpanzees have a higher maximum
      number of DRB genes per haplotype than man. As a consequence, some chimpanzee
      haplotypes must show a dissimilar organization of the MHC DR subregion compared
      to their human equivalents. The implications of these findings are discussed in
      the context of the trans-species theory of MHC polymorphism.

PMID- 1978715
TI  - Localization of a mouse heat shock Hsp70 gene within the H-2 complex.

PMID- 1978716
TI  - Mapping in the mouse of the region homologous to the rat growth and reproduction
      complex (grc).

PMID- 1978717
TI  - Fatigue fractures of the foot.
AB  - While fatigue fractures are common in military practice they are much less so in
      civilian practice and thus tend to be overlooked. Fractures occur most commonly
      in the distal second and third metatarsal shafts and within the calcaneum, but
      occur in almost any other bone of the foot. Any suspicious history of repetitive
      stress or sudden change in activity, athletic or otherwise, associated with
      swelling and point tenderness warrants further investigation by bone
      scintigraphy. Attention is drawn to the importance of understanding the basic
      biomechanical function of the foot and how it may affect the development of
      fatigue fractures. A distinction is drawn between the distal fractures of the
      second and third metatarsal shafts and those occurring in the proximal shafts of
      any of the metatarsals which have a different aetiology. Following conventional
      management in a plaster cast, it is suggested that any biomechanical anomaly
      which is present is compensated appropriately with an orthotic insole.

PMID- 1978718
TI  - Inhibition of 5-HETE, LTB4, and LTC4 formation by azelastine in rat mixed
      peritoneal cells.
AB  - Azelastine produced a concentration-dependent inhibition of calcium ionophore
      A23187 (0.2 microM) stimulated generation of 5-HETE, leukotriene B4, and
      leukotriene C4 in rat mixed peritoneal cells, yielding IC50 values of 35.5, 47.4,
      and 31.7 microM, respectively. Nordihydroguaiaretic acid (a potent 5-lipoxygenase
      inhibitor) also exerted a strong and concentration-dependent inhibition of 5-HETE
      and leukotriene B4 and C4 formation with IC50 values of 0.15, 0.09, and 0.1
      microM, respectively. The inhibition of the formation of the products of the
      lipoxygenase pathway of arachidonic acid metabolism by azelastine may contribute
      to its overall antiallergic, antiasthmatic, and pulmonary anti-inflammatory
      activities.

PMID- 1978719
TI  - Prophylactic antiasthma drugs in Japan.

PMID- 1978720
TI  - The OLE1 gene of Saccharomyces cerevisiae encodes the delta 9 fatty acid
      desaturase and can be functionally replaced by the rat stearoyl-CoA desaturase
      gene.
AB  - Strains of Saccharomyces cerevisiae bearing the ole1 mutation are defective in
      unsaturated fatty acid (UFA) synthesis and require UFAs for growth. A previously
      isolated yeast genomic fragment complementing the ole1 mutation has been
      sequenced and determined to encode the delta 9 fatty acid desaturase enzyme by
      comparison of primary amino acid sequence to the rat liver stearoyl-CoA
      desaturase. The OLE1 structural gene encodes a protein of 510 amino acids (251
      hydrophobic) having an approximate molecular mass of 57.4 kDa. A 257-amino acid
      internal region of the yeast open reading frame aligns with and shows 36%
      identity and 60% similarity to the rat liver stearoyl-CoA desaturase protein.
      This comparison disclosed three short regions of high consecutive amino acid
      identity (greater than 70%) including one 11 of 12 perfect residue match. The
      predicted yeast enzyme contains at least four potential membrane-spanning regions
      and several shorter hydrophobic regions that align exactly with similar sequences
      in the rat liver protein. An ole1 gene-disrupted yeast strain was transformed
      with a yeast-rat chimeric gene consisting of the promoter region and N-terminal
      27 codons of OLE1 fused to the rat desaturase coding sequence. Fusion gene
      transformants displayed near equivalent growth rates and modest lipid composition
      changes relative to wild type yeast control implying a significant conservation
      of delta 9 desaturase tertiary structure and efficient interaction between the
      rat desaturase and yeast cytochrome b5.

PMID- 1978721
TI  - Active-site residues of 2-keto-4-hydroxyglutarate aldolase from Escherichia coli.
      Bromopyruvate inactivation and labeling of glutamate 45.
AB  - Treatment of pure 2-keto-4-hydroxyglutarate aldolase from Escherichia coli, a
      "lysine-type," Schiff-base mechanism enzyme, with the substrate analog
      bromopyruvate results in a time- and concentration-dependent loss of enzymatic
      activity. Whereas the substrates pyruvate and 2-keto-4-hydroxyglutarate provide
      greater than 90% protection against inactivation by bromopyruvate, no protective
      effect is seen with glycolaldehyde, an analog of glyoxylate. Inactivation studies
      with [14C] bromopyruvate show the incorporation of 1.1 mol of 14C-labeled
      compound/enzyme subunit; isolation of a radioactive peptide and determination of
      its amino acid sequence indicate that the radioactivity is associated with
      glutamate 45. Incubation of the enzyme with excess [14C]bromopyruvate followed by
      denaturation with guanidine.HCl allow for the incorporation of carbon-14 at
      cysteines 159 and 180 as well. Whereas the presence of pyruvate protects Glu-45
      from being esterified, it does not prevent the alkylation of these 2 cysteine
      residues. The results indicate that Glu-45 of E. coli 2-keto-4-hydroxyglutarate
      aldolase is essential for catalytic activity, most likely acting as the
      amphoteric proton donor/acceptor that is required as a participant in the overall
      mechanism of the reaction catalyzed.

PMID- 1978722
TI  - The primary structure of the rat guanylyl cyclase A/atrial natriuretic peptide
      receptor gene.
AB  - We have isolated and characterized three genomic clones and a genomic fragment
      amplified by the polymerase chain reaction that contain the rat guanylyl cyclase
      A (GC-A)/atrial natriuretic peptide receptor gene. The gene spans about 17.5
      kilobases and includes 22 exons and 21 introns. All of the exon-intron junction
      sequences coincide with the GT/AG consensus. GC-A consists of at least the
      following four distinguishable domains: extracellular ligand binding,
      transmembrane, kinase-like, and cyclase catalytic. Exon 7 encodes the putative
      transmembrane domain. The kinase-like and catalytic domains are encoded by exons
      8-15 and 16-22, respectively. The 5' end of the transcript, estimated by primer
      extension and S1 mapping, is 370 nucleotides upstream of the methionine
      initiation codon. The initiator sequence (-3 to +5) of CACACTCC has two
      mismatches when compared with a consensus initiator sequence of CTCANTCT. The 5'
      flanking region contains three potential Sp1-binding sites and an inverted CCAAT
      box, but no apparent TATA box. Three different and short interspersed, repetitive
      sequences are found within intervening sequences and within the 5'- and 3'
      flanking regions of the gene (five rat identifier, two rat type 2 Alu equivalent,
      and seven Alu-like sequences). They fall between the four major domains
      suggestive that these may be sites for frequent recombination events. This first
      reported structure of a gene for a member of this new enzyme/receptor family
      should facilitate the search for new family members, as well as allow studies to
      progress on the mechanisms by which the gene is regulated.

PMID- 1978723
TI  - Mouse opsin. Gene structure and molecular basis of multiple transcripts.
AB  - The single copy mouse opsin gene produces five major transcripts, varying in size
      from 1.7 to 5.1 kilobases. The mRNAs are present at levels that vary over 2
      orders of magnitude and can be detected as early as postnatal day 1. Each of the
      transcripts is polyadenylated and can be identified in polysome-bound RNA,
      suggesting that each is translated in vivo. To elucidate the molecular basis of
      this complex transcription pattern, we have characterized genomic fragments
      covering the entire mouse opsin gene, including several kilobases of 5'- and 3'
      flanking regions. Transcription initiates at a single site 97 base pairs upstream
      of the translation start codon. Northern hybridization with exon- and intron
      specific probes demonstrated that the various transcripts are not generated by
      partial or alternative splicing. Sequence analysis of the 3' end of the gene
      showed the presence of multiple polyadenylation signals. Analysis by polymerase
      chain reaction of the 3' end of opsin cDNA demonstrated that the complex
      transcription pattern originated from the selective use of these polyadenylation
      sites, generating transcripts that differ only in the length of the 3'
      untranslated region. Transcript heterogeneity similar to that observed in mouse
      was also found in rat and, to a lesser degree, in human and frog opsin mRNAs.

PMID- 1978724
TI  - Cephalosporin-induced alteration in hepatic glutathione redox state. A potential
      mechanism for inhibition of hepatic reduction of vitamin K1,2,3-epoxide in the
      rat.
AB  - Hypoprothrombinemia is a serious adverse effect of antimicrobial therapy that
      occurs after administration of some second- and third-generation cephalosporins
      which contain the methyltetrazole-thiol (MTT) group. Previous studies have shown
      that in vitro MTT directly inhibits microsomal gamma-carboxylation of a synthetic
      pentapeptide. Since MTT is a thiocarbamide, a type of compound that can increase
      oxidation of glutathione, the present studies were carried out to determine
      whether alterations in hepatic glutathione redox state might interfere with
      vitamin K metabolism. Dose-related increases in biliary efflux and hepatic
      concentration of oxidized glutathione (GSSG) occurred after intravenous
      administration of MTT or MTT-containing antibiotics to rats. This finding
      suggested that these compounds could alter the hepatic glutathione redox state in
      vivo. Microsomal reduction of vitamin K epoxide occurred in the presence of 100
      microM dithiothreitol (DTT), but was inhibited by preincubation with GSSG at
      concentrations as low as 10 microM. At higher concentrations of DTT (1.0 mM)
      inhibition by GSSG persisted, but higher concentrations were required, suggesting
      that the thiol/disulfide ratio, rather than the absolute concentration of GSSG
      was important. By contrast, GSSG did not effect microsomal gamma-carboxylation of
      a pentapeptide, using either vitamin K1 or its hydroquinone as a cofactor. These
      findings suggest a novel mechanism for the hypoprothrombinemia occurring after
      administration of MTT-containing antibiotics.

PMID- 1978726
TI  - Nutrition monitoring and nutrition status assessment. Proceedings of a conference
      held in Charleston, South Carolina, December 8-10, 1989.

PMID- 1978725
TI  - A substitution at a non-glycine position in the triple-helical domain of pro
      alpha 2(I) collagen chains present in an individual with a variant of the Marfan
      syndrome.
AB  - A substitution for a highly conserved non-glycine residue in the triple-helical
      domain of the pro alpha 2(I) collagen molecule was found in an individual with a
      variant of the Marfan syndrome. A single base change resulted in substitution of
      arginine618 by glutamine at the Y position of a Gly-X-Y repeat, and is
      responsible for the decreased migration in SDS-polyacrylamide gels of some pro
      alpha 2(I) chains of type I collagen synthesized by dermal fibroblasts from this
      individual. Family studies suggest that this substitution was inherited from the
      individual's father who also produces abnormally migrating pro alpha 2(I)
      collagen chains and shares some of the abnormal skeletal features. This single
      base change creates a new Bsu36 I (Sau I, Mst II) restriction site detectable in
      genomic DNA by Southern blot analysis when probed with a COL1A2 fragment. The
      analysis of 52 control individuals (103 chromosomes) was negative for the new
      Bsu36 I site, suggesting that the substitution is not a common polymorphism.

PMID- 1978727
TI  - In vivo treatment with benzodiazepines inhibits murine phagocyte oxidative
      metabolism and production of interleukin 1, tumor necrosis factor and interleukin
      6.
AB  - We reported previously that benzodiazepines, widely prescribed for their
      anxiolytic properties, bind to specific receptors on macrophages and modulate in
      vitro their metabolic oxidative responsiveness. This study was designed to
      investigate the in vivo effects of benzodiazepine molecules on several macrophage
      functions. Benzodiazepines injected i.p. exerted a long-lasting inhibition on
      phagocyte oxidative responsiveness, still detectable 48 hr after injection. This
      action was dose-dependent, optimally effective at 1 mg/kg and observed at the
      site of injection within peritoneal cells as well as at a distance, within
      splenocytes. It was restricted to peripheral and mixed-type molecules whereas the
      central-type compound, clonazepam, was ineffective, in good keeping with the
      molecular specificity of the receptor present on murine macrophages. The fact
      that benzodiazepines exerted similar effects in Nude mice highly suggests that
      their in vivo inhibitory activity was not T cell-dependent. The peripheral
      benzodiazepine Ro5-4864 injected i.p. inhibited the capacity of macrophages to
      produce interleukin-1, tumor necrosis factor and interleukin-6. Clonazepam
      remained ineffective. These results demonstrate an in vivo immunosuppressive
      property of peripheral and mixed but not central -type benzodiazepines affecting
      characteristic phagocyte functions involved in host-defense mechanisms as well as
      in inflammatory response.

PMID- 1978728
TI  - Selective 5-hydroxytryptamine2 receptor antagonists protect against the
      neurotoxicity of methylenedioxymethamphetamine in rats.
AB  - The serotonergic deficits resulting from methylenedioxymethamphetamine (MDMA)
      induced neurotoxicity were prevented by the simultaneous administration of 5
      hydroxytryptamine2 (5-HT2) receptor antagonists such as MDL 11,939 or ritanserin.
      This effect was not region specific as protection was observed in the cortex,
      hippocampus and striatum 1 week after the administration of a single dose of
      MDMA. MDL 11,939 also showed some efficacy at reducing the deficits in 5-HT
      concentrations and tryptophan hydroxylase activity produced by multiple
      administrations of MDMA. Protection against the neurotoxicity required the
      administration of MDL 11,939 within 1 hr of MDMA indicating 5-HT2 receptor
      activation was an early event in the process leading to terminal damage.
      Examination of the effect of the 5-HT2 receptor blockade on the early
      neurochemical alterations induced by MDMA revealed an inhibitory effect on MDMA
      stimulated dopamine synthesis. Analysis of these data and the associated changes
      in dopamine metabolites indicates that 5-HT2 receptor antagonists block MDMA
      induced neurotoxicity by interfering with the ability of the dopamine neuron to
      maintain its cytoplasmic pool of transmitter and thereby sustain carrier-mediated
      dopamine release.

PMID- 1978729
TI  - Neuromodulatory effects of atrial natriuretic factor are independent of guanylate
      cyclase in adrenergic neuronal pheochromocytoma cells.
AB  - This study tests the hypothesis that atrial natriuretic factor (ANF) and C-ANF(4
      23)-NH2 (C-ANF) augment cGMP generation and inhibit both cAMP generation and
      depolarization-induced catecholamine release in nerve growth factor treated
      pheochromocytoma cells by a pertussis toxin (PTX)-sensitive mechanism. Synthetic
      rat ANF(99-126) and the clearance receptor antagonist C-ANF (10(-12)-10(-9) M)
      inhibited basal and 5 microM vasoactive intestinal peptide (VIP)-induced cAMP
      generation in a concentration-dependent manner. These actions of ANF and C-ANF
      were blocked by 12-18 h pretreatment with PTX (100 ng/ml), suggesting ANF
      receptor coupling to adenylate cyclase via an inhibitory guanine nucleotide
      binding protein. Both ANF (10(-11)-10(-9) M) and C-ANF (10(-11)-10(-8) M) also
      inhibited K(+)-induced catecholamine release in a concentration-dependent manner.
      ANF (10(-11)-10(-8) M) increased cGMP generation in a concentration-dependent
      manner but C-ANF did not. The accumulation of cGMP in response to ANF was not
      altered by treatment with PTX. Therefore, PTX dissociated the increased
      concentrations of cGMP from the ANF-mediated depression of evoked catecholamine
      release. C-ANF also dissociated elevations in cGMP concentrations from an ANF
      mediated attenuation of evoked catecholamine release. The results of this study
      indicate that ANF inhibits adrenergic neurotransmission independent of guanylate
      cyclase.

PMID- 1978730
TI  - Pharmacokinetics, anticonvulsant efficacy and adverse effects of the beta
      carboline abecarnil, a novel ligand for benzodiazepine receptors, after acute and
      chronic administration in dogs.
AB  - Abecarnil (ZK 112119; isopropyl-6-benzyloxy-4-methoxymethyl-beta-carboline-3
      carboxylate), a novel beta-carboline with high affinity for central
      benzodiazepine (BZ) receptors, has been shown recently to be a potent anxiolytic
      and anticonvulsant in animal models whereas lacking ataxia-producing effects, a
      profile typical for a partial agonist at BZ receptors. In the present study
      abecarnil was tested in dogs after acute and chronic administration.
      Pharmacokinetic studies showed that abecarnil was eliminated rapidly after i.v.
      or p.o. administration, but elimination was delayed substantially after s.c.
      injection. After i.v. injection, the drug penetrated rapidly into the
      cerebrospinal fluid, but maximum concentrations reached in cerebrospinal fluid
      were only 6 to 8% of those in plasma. Anticonvulsant potency of abecarnil in dogs
      was studied by means of seizures induced by i.v. infusion of pentylenetetrazol.
      After i.v. administration of single doses, abecarnil was about half as potent as
      diazepam, dose-dependently increasing the pentylenetetrazol threshold by doses of
      0.1-1 mg/kg. In contrast to diazepam, most dogs injected with abecarnil at
      anticonvulsant doses showed no ataxia. During chronic s.c. administration of
      abecarnil for 6 weeks, the anticonvulsant efficacy of the drug increased markedly
      during the first week(s) of treatment, possibly indicating drug accumulation in
      the brain. During the subsequent weeks of treatment, there was a slight reduction
      in anticonvulsant potency. No withdrawal symptoms were observed after cessation
      of the 6-week administration period. Furthermore, injection of the BZ antagonist
      Ro 15-1788 (flumazenil), 1 mg/kg i.v., after 5 weeks of treatment did not
      precipitate withdrawal symptoms except slight tremor in two of seven dogs
      studied.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1978731
TI  - Precipitated abstinence in orally dosed benzodiazepine-dependent dogs.
AB  - The ability of graded doses of flumazenil (2, 6, 18, 36 and 72 mg/kg) and a
      lactose placebo to precipitate abstinence was studied in dogs treated chronically
      with diazepam, nordiazepam, flunitrazepam, alprazolam, oxazepam, halazepam and
      lorazepam by oral dosing. A scale comprised of 10 precipitated abstinence signs,
      the Benzodiazepine Precipitated Abstinence Scale, was developed, which yielded
      linear flumazenil log-dose response lines with significant slopes in dogs
      dependent on diazepam, nordiazepam and flunitrazepam. The effects of 18, 36 and
      72 mg/kg of flumazenil in otherwise drug naive dogs were studied. In naive dogs,
      the most prominent effect of flumazenil was to reduce activity. All
      benzodiazepines studied produced dependence that was characterized by signs of
      precipitated abstinence; however, the intensity and quality of abstinence varied
      from one benzodiazepine to another. Precipitated abstinence in dogs treated
      chronically with diazepam and flunitrazepam was characterized by a dose-related
      increase in clonic convulsions and Benzodiazepine Precipitated Abstinence Scale
      scores. This pattern differed from that seen in nordiazepam- and alprazolam
      dependent dogs, which showed a comparable flumazenil dose-related increase in
      clonic convulsion but only a modest increase in Benzodiazepine Precipitated
      Abstinence Scale scores. Oxazepam and lorazepam produced dependence that was less
      intense than that seen with the other benzodiazepines. Plasma levels of the
      benzodiazepines and their metabolites were repeatedly determined after single
      doses and during addiction cycles. Nordiazepam accumulated in diazepam- and
      nordiazepam-dependent dogs and alpha-OH alprazolam accumulated in alprazolam
      dependent dogs. Other drugs and metabolites did not. These observations suggest
      that: 1) different benzodiazepines or their metabolites produce different types
      of physical dependence, suggesting that they or their metabolites have different
      mechanisms and sites of action; 2) plasma cumulation of the benzodiazepines or
      their active metabolites is an important factor in the genesis of physical
      dependence; and 3) metabolism of benzodiazepines plays an important role in their
      dependence-producing capacity, and because of differences in the way species
      metabolize benzodiazepines, the type of dependence produced in different species
      may differ.

PMID- 1978732
TI  - Augmentation of release of gastric somatostatin-like immunoreactivity by
      adenosine, adenosine triphosphate and their analogs.
AB  - The effect of adenosine, adenosine 5'-triphosphate (ATP) and ATP analogs on basal
      gastric somatostatin-like immunoreactivity (SLI) release was studied using the
      vascularly perfused rat stomach. The release of gastric SLI was stimulated by
      adenosine (0.6-60 microM) concentration dependently, while the release of
      immunoreactive gastrin was inhibited by 1 and 10 microM adenosine. The
      stimulatory action of adenosine was probably mediated by adenosine receptors
      because the receptor antagonist, 8-phenyltheophylline, abolished the action of
      adenosine. In addition, the adenosine-induced release of SLI was not mediated by
      a cholinergic or beta-adrenergic mechanism, since atropine, hexamethonium or
      propranolol did not block the action of adenosine. Dipyridamole enhanced the
      adenosine-stimulated, but not 2-chloroadenosine-induced SLI release. Since the
      adenosine analog, 2-chloroadenosine, is resistant to the adenosine uptake
      mechanism, it is likely that adenosine-stimulated release of gastric SLI is due
      to the activation of extracellular receptors. ATP also stimulated gastric SLI
      release. The analogs alpha,beta-methyleneadenosine triphosphate and diphosphate,
      which are resistant to metabolic breakdown, did not stimulate basal SLI release,
      while gamma,beta-methyleneadenosine triphosphate, which can be metabolized,
      increased the release of SLI. In addition, the ATP-induced release of SLI was
      abolished by 8-phenyltheophylline. Therefore, the action of ATP is likely to be a
      result of its metabolism to adenosine.

PMID- 1978733
TI  - Nonopioid actions of the kappa-opioid receptor agonists, U 50488H and U 69593 on
      electrophysiologic properties of hippocampal CA3 neurons in vitro.
AB  - The actions of the nonpeptide kappa-opioid receptor agonists, U 50488H (1-100
      microM) and U 69593 (50-200 microM), on guinea pig hippocampal CA3 neurons were
      investigated in vitro by means of intra- and extracellular recording techniques.
      The compounds reduced the efficacy of synaptic transmission at the mossy fiber
      CA3 synapse, and, simultaneously, enhanced the neuronal direct excitability.
      Intracellular recordings from CA3 neurons suggested two components underlying the
      drugs' excitatory actions: 1) Due to an apparent decrease in membrane leak
      conductance, the compounds enhanced the neuronal input resistance in a dose
      dependent fashion. 2) The fast after-hyperpolarization following spontaneous or
      evoked action potentials was found to be substantially impaired in the presence
      of the drugs. In addition, extra- and intracellular recordings provided evidence
      that, by reducing the fast sodium conductance, both compounds exerted a local
      anesthetic action. The effects of U 50488H were antagonized neither by naloxone
      (2-50 microM) nor by the kappa-opioid receptor antagonist, nor-binaltorphimine
      (10-20 microM), indicating that the drug-induced effects represent unspecific
      actions not linked to activation of opioid receptors.

PMID- 1978734
TI  - Rotavirus-specific cytotoxic T lymphocytes passively protect against
      gastroenteritis in suckling mice.
AB  - Suckling mice are protected against murine rotavirus-induced gastroenteritis
      after adoptive transfer of splenic lymphocytes from immunized animals. Adoptive
      transfer of Thy1(+)-depleted or CD8(+)-depleted lymphocytes abrogated protection
      against challenge. (We previously found that depletion of Thy1+ or CD8+
      lymphocytes from rotavirus-immunized mice decreased rotavirus-specific cytotoxic
      activity in vitro.) Protection against disease occurred in the absence of
      rotavirus-specific neutralizing antibodies in the sera of suckling mice.
      Rotavirus-specific cytotoxic T lymphocytes may be important in either
      amelioration of acute infection or protection against reinfection.

PMID- 1978735
TI  - Suitability of colchicine and superoxide dismutase for the suppression of renal
      scarring following an infection with bacteria showing mannose-sensitive pili.
AB  - Two new strains of Serratia marcescens were constructed by the gene manipulation
      method from the clinical isolate US 46, which has two kinds of pili--mannose
      sensitive (MS) and mannose-resistant (MR) ones--on the cell surface. After
      cloning the genes of the MS and MR pili, either the MS or the MR gene was
      transferred to the nonpiliated Escherichia coli, and MS- or MR-piliated strains
      were obtained. In the experimental pyelonephritis model of rats, MS- or MR
      piliated bacteria were inoculated directly to the renal parenchyma, and the
      following results were obtained. MS-piliated rather than MR-piliated strains
      stimulated severe scarring of the kidney, and this scarring was suppressed by
      treatment with colchicine or superoxide dismutase (SOD) during an early stage of
      the infection. These findings suggest that MS-piliated bacteria stimulated
      polymorphonuclear leukocytes, which released large amounts of superoxide
      resulting in renal scarring. SOD was hoped to be a drug capable of preventing
      renal scarring, and such a result was successfully obtained.

PMID- 1978736
TI  - Renal and endocrine effects of fenoldopam and metoclopramide in normal man.
AB  - The effects of fenoldopam (FD), a selective dopamine-1 (DA1) agonist in doses
      from 0.05 to 0.50 micrograms/kg/min and of the aselective dopamine antagonist
      metoclopramide (MCP) on blood pressure (BP), sodium excretion and renal
      hemodynamics were investigated in 10 healthy volunteers. During FD infusion the
      diastolic BP fell 9 mm Hg with a rise in heart rate. During combined infusion of
      FD and MCP no changes in BP occurred. Effective renal plasma flow rose for all
      doses of FD with a maximal increase of 36% and was not influenced by MCP
      infusion. Glomerular filtration rate remained unchanged. FD induced an increase
      in sodium and calcium excretion compared to placebo study, which was abolished by
      MCP. A marked rise of plasma renin activity during FD infusion was noted, blunted
      by MCP. MCP induced a marked increase of aldosterone, sustained, but blunted,
      during subsequent FD infusion, suggesting a DA1-mediated influence on aldosterone
      secretion. During infusion of FD alone, an increased urinary dopamine excretion
      was observed. We conclude that FD induces: (1) systemic and renal vasodilation
      and (2) natriuresis by direct stimulation of DA1 receptors in the proximal
      tubule, which is (partially) counteracted by a rise of plasma renin activity and
      subsequently of aldosterone.

PMID- 1978737
TI  - Muscarinic receptor activation attenuates D2 dopamine receptor mediated
      inhibition of acetylcholine release in rat striatum: indications for a common
      signal transduction pathway.
AB  - In the present investigations, we used a superfusion system to study the effect
      of simultaneous activation of D2 dopamine receptors and so-called muscarinic
      "autoreceptors" on the K(+)-evoked in vitro release of [3H]acetylcholine from rat
      striatal tissue slices. Activation of D2 receptors with the selective agonist LY
      171555 (0.01-1 microM) clearly decreased the evoked release of [3H]acetylcholine.
      This effect was markedly attenuated in the presence of either the selective
      muscarinic receptor agonist oxotremorine (3 microM) or the cholinesterase
      inhibitor physostigmine (1 microM). Conversely, D2 receptor activation with LY
      171555 (1 microM) completely abolished the muscarinic receptor mediated
      inhibition of evoked [3H]acetylcholine release induced by oxotremorine (0.03-10
      microM). These results show that the inhibitory effects of D2 dopamine receptor
      and muscarinic receptor activation on striatal acetylcholine release are non
      additive and therefore are interdependent processes. In addition, we investigated
      some aspects of the signal transduction mechanism by which the muscarinic
      receptor mediates inhibition of K(+)-evoked in vitro release of [3H]acetylcholine
      from rat striatal tissue slices. It appeared that the effect of muscarinic
      receptor activation was not significantly influenced either by a lowering of the
      extracellular Ca2+ concentration from the usual 1.2-0.12 mM or by an increase of
      the intracellular cyclic adenosine-3',5'-monophosphate content. However,
      increasing extracellular K+ strongly decreased the inhibition of evoked
      [3H]acetylcholine release mediated by activation of muscarinic receptors. This
      set of results indicates that the muscarinic "autoreceptor" mediates the decrease
      of depolarization induced [3H]acetylcholine release from rat striatum to a large
      extent through stimulation of K+ efflux (opening of K+ channels) in a cyclic
      adenosine-3',5'-monophosphate independent manner.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1978739
TI  - Development of cholinergic traits in the quail ciliary ganglion: expression of
      choline acetyltransferase-like immunoreactivity.
AB  - The avian ciliary ganglion is a parasympathetic ganglion derived from the neural
      crest whose neurons provide cholinergic innervation to the eye. Here, we describe
      the time course of appearance and the morphology of cholinergic cells in the
      ciliary ganglion, as assessed by antibodies against choline acetyltransferase.
      Choline acetyltransferase immunoreactivity was first observed in 5.5-day-old
      quail embryos, 1 day after condensation of the ciliary ganglion. Both the
      intensity of choline acetyltransferase immunoreactivity and size of the choline
      acetyltransferase-immunoreactive cells increased with ganglionic age. By 12 days,
      a second population of choline acetyltransferase-immunoreactive cells, possibly
      corresponding to choroid neurons, was observed whose cells were smaller and less
      intensely stained than earlier differentiating choline acetyltransferase
      immunoreactive cells. The percentage of choline acetyltransferase-immunoreactive
      cells was initially high, constituting approximately 50% of the total cell
      population. As a function of time, the proportion of cholinergic cells decreased,
      probably due to proliferation of non-neuronal cells and naturally-occurring cell
      death. Our results confirm the existence of two morphologically distinct
      populations of cholinergic neurons in the avian ciliary ganglion and demonstrate
      that these neuronal subpopulations express choline acetyltransferase
      immunoreactivity at different times in development. Because choroid neurons
      innervate their targets later than ciliary neurons, this finding is consistent
      with the hypothesis that target interactions regulate expression of choline
      acetyltransferase.

PMID- 1978738
TI  - Synaptic transmission in the guinea-pig vas deferens: the role of nerve action
      potentials.
AB  - To determine how transmitter release is related to presynaptic nerve activities,
      pre- and postsynaptic electrical events of the vas deferens in the guinea-pig
      were recorded with a suction electrode. Stimulation of the hypogastric nerve
      elicited excitatory junction currents and nerve action potentials. Intermittence
      of excitatory junction currents was observed. In some instances, this was related
      to the absence of nerve action potentials, suggesting failure of impulse
      propagation into the nerve terminals. Facilitation of both the nerve action
      potentials and the excitatory junction currents was also observed. Internal
      perfusion of the recording electrode with tetrodotoxin blocked the nerve impulse,
      and the polarity of the excitatory junction current became positive. Similar
      effects on the polarity of the excitatory junction current were observed with
      alpha, beta-methylene ATP. Perfusion of the suction pipette with 4-aminopyridine
      or tetraethylammonium increased the amplitude of the excitatory junction currents
      and prolonged the nerve action potential duration. These experiments show that:
      (1) transmission failure in some cases can be related to conduction block into
      the terminal region: (2) facilitation of excitatory junction currents may be
      related to facilitation of the nerve action potentials; (3) enhancement of
      transmitter release by potassium channel blockers may be related to prolongation
      of the duration of the nerve action potential. It is concluded that transmitter
      release is intimately related to presynaptic nerve activities.

PMID- 1978740
TI  - Innervation of different peptide-containing neurons in the hippocampus by
      GABAergic septal afferents.
AB  - The termination pattern of septohippocampal axons visualized by anterograde
      transport of Phaseolus vulgaris leucoagglutinin was studied in the hippocampal
      formation in the rat, with special reference to the innervation of neurons
      immunoreactive for the neuroactive peptides cholecystokinin, somatostatin or
      vasoactive intestinal polypeptide. The type I, GABAergic, septohippocampal
      afferents were shown to terminate on neurons immunoreactive for each of the three
      peptides. The cholecystokinin-like immunoreactive neurons in all regions, and the
      somatostatin-immunoreactive cells in stratum oriens of CA1 region were the most
      preferred targets. Cholecystokinin-immunoreactive cells, especially those in the
      granule cell layer of the dentate gyrus, were often seen to be contacted by type
      II (presumed cholinergic) axons as well. The somatostatin-immunoreactive cells in
      the hilus were also innervated by type I septohippocampal axons, although less
      frequently than those in stratum oriens of the CA1 subfield. Each type of
      peptidergic neuron received multiple symmetrical synaptic input from the
      Phaseolus vulgaris leucoagglutinin-labelled septal afferents, as confirmed by
      correlated electron microscopy. The majority of these neuropeptide-containing
      cells are known to be GABAergic, and to have distinct input and output
      relationships. Thus, the present results demonstrate that the GABAergic
      septohippocampal pathway can control a wide range of putative inhibitory
      circuits, and thereby influence the pattern of electrical activity in the
      hippocampal formation.

PMID- 1978741
TI  - Stimulation of endogenous opioid release displaces mu receptor binding in rat
      hippocampus.
AB  - Physiological release of endogenous opioids in the rat hippocampus was detected
      by an in vitro radioligand displacement assay using [3H][D-Ala2,N-methyl
      Phe4,glyol5]enkephalin ([3H]DAGO), a mu selective opioid agonist. In this assay,
      radioligand binding to opioid receptors in the in vitro hippocampal slice was
      reduced by competition with endogenous opioids released following tissue
      depolarization. Veratridine-induced opioid release caused displacement of
      [3H]DAGO that could be blocked by either tetrodotoxin addition or calcium removal
      from the incubation buffer. Maximal displacement of [3H]DAGO also required the
      presence of peptidase inhibitors in the incubation buffer. None of the buffer
      composition changes directly affected [3H]DAGO binding to rat brain membranes.
      Calcium-dependent displacement of [3H]DAGO binding from mu receptor sites
      elicited by focal electrical stimulation depended on the intensity and frequency
      of stimulation and positioning of the electrode in the slice. Maximal
      displacement of [3H]DAGO binding was observed following high intensity (150-300
      microA), high frequency (10-50 Hz) stimulation of the perforant path, a major
      afferent fiber system to the hippocampus previously shown to contain
      proenkephalin-derived opioids. Low frequency stimulation (0.1-1 Hz) was
      ineffective. Stimulation of the mossy fibers (containing both dynorphins and
      enkephalins) also significantly reduced mu receptor binding, but to a lesser
      extent. Electrical stimulation of the hippocampal slice at sites not containing
      opioid peptides did not cause mu receptor displacement. These results demonstrate
      that under physiological conditions, the release of endogenous opioids from the
      major opioid containing pathways can be detected in a single hippocampal slice
      following high frequency stimulation.

PMID- 1978743
TI  - Changes in field excitatory postsynaptic potential shape induced by tetanization
      in the CA1 region of the guinea-pig hippocampal slice.
AB  - The present paper contains a description of a prolonged potentiation of the field
      excitatory postsynaptic potential in the CA1 region of the hippocampal slice
      preparation following afferent tetanization. In contrast to long-term
      potentiation, this novel potentiation is not specific to the activated synapses,
      and manifests itself as a change in the shape of the field excitatory
      postsynaptic potential with a prolongation of the rising phase and an increased
      peak amplitude. The potentiation is fully developed within minutes after
      tetanization and shows no decrement for at least an hour. Although it can appear
      together with long-term potentiation following tetanization at moderate strength
      (single volley excitatory postsynaptic potential below threshold for spike
      initiation), it is more readily seen following tetanization at higher strengths.
      The N-methyl-D-aspartate receptor antagonist 2-amino-5-phosphonovalerate prevents
      the induction but not the maintenance of the shape modification. The potentiation
      is observed in the presence of the GABAA antagonist picrotoxin (100 microM) and
      is thus not secondary to changes in postsynaptic inhibition. 4-Aminopyridine (50
      100 microM) produced changes in the field excitatory postsynaptic potential
      resembling the shape modification produced by afferent tetanization, suggesting
      that the potentiation may be due to a blockade of potassium channels, pre- or
      postsynaptically located. The potentiation is also found to be associated with an
      increase in the population spike for a given initial slope of the field
      excitatory postsynaptic potential, and may thus contribute to the excitatory
      postsynaptic potential-spike potentiation that can be observed following afferent
      tetanization.

PMID- 1978742
TI  - Activators of ATP-sensitive K+ channels reduce anoxic depolarization in CA3
      hippocampal neurons.
AB  - In CA3 hippocampal neurons of the rat, brief anoxic episodes produce a
      depolarization which is probably due to a synaptic release of glutamate.
      Diazoxide, an activator of ATP-sensitive K+ channels (K+ ATP), blocks the anoxic
      depolarization and has no effect in control oxygenated artificial cerebrospinal
      fluid. The hormone somatostatin which activates K+ ATP channels in the pancreas
      also reduces the anoxic depolarization in CA3 neurons. We suggest that drugs that
      open K+ ATP channels may constitute a novel approach to selectivity reducing the
      deleterious effects of excessive release of glutamate during anoxia without
      producing a generalized blockade of glutamatergic synaptic transmission.

PMID- 1978744
TI  - Glutamate-mediated selective vulnerability to ischemia is present in organotypic
      cultures of hippocampus.
AB  - Ischemic damage to the brain, whether induced experimentally or observed
      clinically, often produces a pattern of delayed selective cell death in subfield
      CA1 of hippocampus which has been associated with significant neurologic
      deficits. The present study demonstrates that this selective vulnerability of CA1
      neurons to ischemia, with relative preservation of their neighbors, is expressed
      in organotypic tissue culture and is prevented by the N-methyl-D-aspartate (NMDA)
      receptor blocker, MK-801. These data provide conclusive evidence that this
      selective cell death does not have a vascular etiology but is mediated by factors
      intrinsic to the hippocampal neurons and/or local circuitry. This model system
      provides an opportunity both to examine mechanisms of ischemic cell death in an
      avascular environment and to study methods of prevention in the absence of
      systemic variables.

PMID- 1978745
TI  - Evidence that histamine is the inhibitory transmitter of the auditory interneuron
      ON1 of crickets.
AB  - The omega neurons of crickets are connected with each other by reciprocal
      inhibition. This inhibition could be mimicked by bath-applied histamine and
      blocked by histamine H1-antagonists. Histamine, like ON1, also influenced the
      ascending interneuron AN2, so that its response pattern more closely reflected
      the temporal structure of the calling song. This evidence strongly suggests that
      histamine is the inhibitory transmitter of the ON1s.

PMID- 1978746
TI  - Regulation of cGMP metabolism in frog rods.

PMID- 1978747
TI  - Beta agonists and asthma.

PMID- 1978748
TI  - [The effect of somatostatin in dumping syndrome].
AB  - The effect of cyclic somatostatin on early and late dumping syndrome was studied
      in 12 patients with gastric resection. Each patient underwent two glucose
      challenges with 75 grams of glucose administered orally. In the control study
      isotonic sodium chloride was given, while in the other study cyclic somatostatin
      in a dose of 250 micrograms bolus injection followed by infusion of 80 ng/kg/min
      for a period of 270 minutes. In the control study all patients showed subjective
      symptoms of the early dumping syndrome with significant increases in pulse rate,
      hematocrit, and vasoactive intestinal polypeptide. Ten patients showed
      asymptomatic hypoglycemia, as a sign of the late dumping syndrome associated with
      a significant increases of insulin, gastric inhibitory peptide and glucagon
      levels. During the administration of somatostatin these changes failed to
      develop. These results indicate that somatostatin alleviates the symptoms of
      early and late postprandial dumping syndrome.

PMID- 1978750
TI  - Detection of CD2 polymorphism on chromosome 1 with EcoRI.

PMID- 1978751
TI  - Dinucleotide repeat polymorphism at the D18S35 locus.

PMID- 1978752
TI  - Hirsutism and hyperprolactinemia.

PMID- 1978749
TI  - Genetic exchange between endogenous and exogenous LINE-1 repetitive elements in
      mouse cells.
AB  - The repetitive LINE (L1) elements of the mouse, which are present at about 10(5)
      copies per genome and share over 80% of sequence homology, were examined for
      their ability to undergo genetic exchange with exogenous L1 sequences. The
      exogenous L1 sequences, carried by a shuttle vector, consisted of an internal
      fragment from L1Md-A2, a previously described member of the L1 family of the
      mouse. Using an assay that does not require the reconstitution of a selectable
      marker we found that this vector, in either circular or linear form, acquired DNA
      sequences from endogenous L1 elements at a frequency of 10(-3) to 10(-4) per
      rescued vector. Physical analysis of the acquired L1 sequences revealed that
      distinct endogenous L1 elements acted as donors and that different subfamilies
      participated. These results demonstrate that L1 elements are readily capable of
      genetic exchange. Apart from gene conversion events, the acquisition of L1
      sequences outside the region of homology suggested that a second mechanism was
      also involved in the genetic exchange. A model which accounts for this mechanism
      is presented and its potential implication on the rearrangement of L1 elements is
      discussed.

PMID- 1978753
TI  - CSF neuropeptide Y in alcoholics and normal controls.
AB  - Neuropeptide Y is found in brain tissue. In dogs it has been shown to enhance
      activation of the hypothalamic-pituitary-adrenal axis by corticotropin-releasing
      hormone. It is localized in certain catecholamine neurons and to some extent
      colocalized with somatostatin. Disturbances of the central noradrenergic system
      may underlie some forms of alcoholism. Therefore, we compared male alcoholics and
      normal controls on cerebrospinal fluid (CSF) levels of neuropeptide Y. There was
      no significant difference between the two groups for neuropeptide Y. There was
      also no significant difference for CSF levels of growth hormone releasing
      hormone. However, there were significant positive correlations between CSF levels
      of neuropeptide Y and CSF levels of corticotropin-releasing hormone,
      somatostatin, and growth hormone releasing hormone.

PMID- 1978754
TI  - [Isotopic radioangiography in hepatic cirrhosis. Changes induced by
      somatostatin].
AB  - The value of first step isotopic angiography (FSIA) with 99-TC in the study of
      altered liver kidney and spleen circulation in patients with liver cirrhosis and
      alcoholic hepatitis is analyzed. This technique is used to evaluate the effect of
      a 250 mcg IV bolus of somatostatin on the activity/time curve at the three
      circulatory levels. The ratio of basal hepatic artery/portal flow in cirrhotics
      was 59 + 11/41 + 11% and 39 + 6/61 + 4 in alcoholic hepatitis, significantly
      different from normal controls (p less than 0.001). In cirrhotics the degree of
      alteration in FSIA correlated with the severity of liver disease. Somatostatin
      significantly improved the ratio of basel hepatic artery/portal flow and
      diminished the pressure at the root of suprahepatic veins (18.5 +/- - v.s. 16 +/-
      mmHg, p greater than 0.001). Neither the slopes nor the time of maximum isotopic
      activity of renal and splenic activity/time curves were modified. We concluded
      highlighting the clinical value of FSIA as a non invasive test in the study of
      chronic liver diseases.

PMID- 1978755
TI  - The beta-adrenergic system in man: physiological and pathophysiological response.
      Regulation of receptor density and functioning.
AB  - Catecholamines play an essential role in the activation of the cardiovascular
      system and in the regulation of energy metabolism in a variety of physiological
      conditions. Many of these effects are mediated through beta-adrenoceptors located
      on cell membranes. Binding of catecholamines to beta-adrenoceptor increases the
      concentration of intracellular cyclic AMP which in turn activates protein kinase
      A. This enzyme phosphorylates a number of other intracellular enzymes influencing
      cell metabolism and functions. The primary structures of the receptor and its
      topography in the cell membrane as well as its binding domains have been
      partially clarified. In studies of the human beta-adrenergic receptors blood
      lymphocytes have mostly been used as model cells. These cells carry receptors of
      mainly the beta 2-subtype. The adequacy of this model system has been
      demonstrated in several studies. In clinical work receptor assays have had
      limited use until now. However, studies on the pathophysiology of the adrenergic
      system in several diseases have revealed that receptor alterations may constitute
      an important factor in the disease process. Measurements of adrenergic receptors
      may also have increasing usefulness in determining optimal drug concentrations.
      Our own studies have primarily focused on physiological adjustments in the beta
      adrenergic system during acute or prolonged physical exercise as well as receptor
      changes in heart failure, muscle diseases and the alcohol withdrawal syndrome. We
      have also explored receptor dynamics during therapy with beta-blocking agents.
      These studies, briefly reviewed in this communication, have led to the following
      conclusions: (1) High aerobic capacity is associated with an increased density
      and ability of lymphocytic beta-adrenoceptors to respond to catecholamines. (2)
      Both short-and long-term physical exercise induce a rapid up-regulation and more
      effective functioning of lymphocytic beta-adrenoceptors. (3) Administration of
      beta-blocking drugs is associated with a subnormal exercise-induced up-regulation
      and decreased functioning of the lymphocytic beta-adrenoceptors. (4) The exercise
      provoked up-regulation and improved functioning of beta-adrenoceptors is blunted
      in heart failure patients. (5) Patients with Duchenne-type of muscular dystrophy
      have a reduced number of lymphocytic beta-adrenoceptors. (6) In chronic
      alcoholics the lymphocytic beta-adrenoceptor level is subnormal but during abrupt
      ethanol withdrawal a rapid increase in the number and functioning of the
      receptors to a normal level takes place. This sequence of events may lead to a
      condition of relative adrenergic hypersensitivity.

PMID- 1978756
TI  - [Effect of cysteamine on the exhaustion of somatotropin release inhibiting
      hormone and its mechanism].

PMID- 1978757
TI  - Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and
      other neoplasms.
AB  - Familial cancer syndromes have helped to define the role of tumor suppressor
      genes in the development of cancer. The dominantly inherited Li-Fraumeni syndrome
      (LFS) is of particular interest because of the diversity of childhood and adult
      tumors that occur in affected individuals. The rarity and high mortality of LFS
      precluded formal linkage analysis. The alternative approach was to select the
      most plausible candidate gene. The tumor suppressor gene, p53, was studied
      because of previous indications that this gene is inactivated in the sporadic
      (nonfamilial) forms of most cancers that are associated with LFS. Germ line p53
      mutations have been detected in all five LFS families analyzed. These mutations
      do not produce amounts of mutant p53 protein expected to exert a trans-dominant
      loss of function effect on wild-type p53 protein. The frequency of germ line p53
      mutations can now be examined in additional families with LFS, and in other
      cancer patients and families with clinical features that might be attributed to
      the mutation.

PMID- 1978758
TI  - Recognition by human V gamma 9/V delta 2 T cells of a GroEL homolog on Daudi
      Burkitt's lymphoma cells.
AB  - All human gamma delta T cells coexpressing the products of the variable (V)
      region T cell receptor (TCR) gene segments V gamma 9 and V delta 2 recognize
      antigens from mycobacterial extracts and Daudi cells. Exogenous and endogenous
      ligands on the cell surface, homologous to the groEL heat shock family, induced
      reactivities that resembled superantigen responses in this major subset of human
      peripheral blood gamma delta T cells. Stimulation of human V gamma 9/V delta 2 T
      cells is not restricted by human leukocyte antigens (HLA), including
      nonpolymorphic beta 2-microglobulin (beta 2M)-associated class Ib molecules.
      These data may be important for understanding the role of gamma delta T cells in
      autoimmunity and in responses to microorganisms and tumors.

PMID- 1978760
TI  - [HLA-DR positive T cells and CD45R positive CD4 cells in primary Sjogren's
      syndrome].
AB  - In 55 patients with primary Sjogren's syndrome (PSJS), we studied on peripheral
      HLA-DR positive T cells, suppressor inducer (CD4 + CD45R) cell and helper inducer
      (CD4 + CDw29) cells by 2-color analysis using flow cytometry system. As shown in
      systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), progressive
      systemic sclerosis and myositis, the rate of pheripheral HLA-DR positive T cells
      in PSJS (5.9% +/- 3.9) was significantly higher than in normal (1.6% +/- 1.1).
      The rate of CD4 +/- CD45R + cells in PSJS (12.8% +/- 6.1) and SLE (12.8% +/- 8.2)
      were significantly lower than in normal (16.6% +/- 3.9). With respect to the
      disease pattern of PSJS, the increase of HLA-DR positive T cell and decrease of
      CD4 + CD45R cell were recognized in patients with leucopenia, high titer of anti
      RNP antibody and/or abnormal findings of sialography, and the decrease of CD4 +
      CD45R + cell was not recognized in patients with kerato-conjunctivitis sicca
      alone. In either SLE or RA, there were no correlations between the rate of T cell
      subsets (HLA-DR positive T cells and CD4 + CD45R cells) and the degree of
      salivary gland damage. T cell subsets in PSJS were useful indicators of disease
      severity and it is also useful for classifying PSJS into several subtypes. To
      analyze T cell surface markers in PSJS is very important for investigation of
      functions of lymphocytes in this disease.

PMID- 1978759
TI  - Glutamate, the dominant excitatory transmitter in neuroendocrine regulation.
AB  - Glutamate has been found to play an unexpectedly important role in neuroendocrine
      regulation in the hypothalamus, as revealed in converging experiments with
      ultrastructural immunocytochemistry, optical physiology with a calcium-sensitive
      dye, and intracellular electrical recording. There were large amounts of
      glutamate in boutons making synaptic contact with neuroendocrine neurons in the
      arcuate, paraventricular, and supraoptic nuclei. Almost all medial hypothalamic
      neurons responded to glutamate and to the glutamate agonists quisqualate and
      kainate with a consistent increase in intracellular calcium. In all magnocellular
      and parvocellular neurons of the paraventricular and arcuate nuclei tested, the
      non-NMDA (non-N-methyl-D-aspartate) glutamate antagonist CNQX (cyano-2,3
      dihydroxy-7-nitroquinoxaline) reduced electrically stimulated and spontaneous
      excitatory postsynaptic potentials, suggesting that the endogenous
      neurotransmitter is an excitatory amino acid acting primarily on non-NMDA
      receptors. These results indicate that glutamate plays a major, widespread role
      in the control of neuroendocrine neurons.

PMID- 1978761
TI  - [Renal damage associated with rheumatoid diseases].

PMID- 1978762
TI  - Virologic and immunologic aspects of acquired immunodeficiency syndrome.
AB  - From the initial clinical descriptions of the acquired immunodeficiency syndrome
      (AIDS) in 1981 to the present time, much has been discovered concerning the
      epidemiologic factors, pathogenesis, treatment and prevention of this disease.
      Recent advances in epidemiology have included a better understanding of the
      occupational risk of human immunodeficiency virus (HIV) infection after
      percutaneous exposure (responsible for approximately 0.4 per cent of instances),
      an appreciation of the potential variability in the time interval between
      infection and seroconversion (generally on the order of three months but
      occasionally longer) and establishment of the need for intimate contact to
      transmit infection. Following the discovery of HIV-1 as the etiologic agent of
      AIDS, many rapid advances have been possible including the development of
      screening tests, elucidation of the HIV-1 genome and the discovery that the CD4 T
      lymphocyte is the predominant cell destroyed by HIV-1. Progressive destruction of
      CD4 T cells results in a progressive decline in immunologic function that may
      take a variety of clinical forms, ranging from no symptoms to severe
      opportunistic infections. The delineation of the life cycle of HIV-1 has helped
      in the development of antiretroviral therapies, including agents that interfere
      with reverse transcription (nucleoside analogues, such as zidovudine,
      dideoxycytidine, dideoxyinosine and azidodideoxyuridine) and agents that
      interfere with viral assembly (protease inhibitors and interferon alpha). A more
      precise understanding of the nature of the immune response elicited after HIV-1
      infection has resulted in the development of several candidate HIV-1 vaccines,
      including recombinant vaccinia viruses expressing the HIV-1 envelope and
      recombinant envelope proteins.

PMID- 1978763
TI  - Magnetic resonance imaging and the nonoperative treatment of spinal epidural
      abscess.
AB  - This report describes three patients with spinal epidural abscess diagnosed by
      magnetic resonance imaging and treated nonoperatively. Prior to treatment, one
      patient was neurologically intact, one patient demonstrated a moderate
      neurological deficit, and one patient was severely paraparetic with loss of
      bladder and bowel control. Following identification of the pathogenic organism,
      antibiotic therapy was continued until the patients demonstrated clinical
      improvement and radiological resolution of the abscess. All patients remained
      stable or improved neurologically. Analysis of 33 previously reported patients
      treated with antibiotics suggests that nonoperative treatment may be a reasonable
      alternative therapy under certain clinical conditions. These include (1)
      identification of the pathogenic organism, (2) a stable neurological condition,
      (3) access to magnetic resonance imaging or computed tomography for potentially
      rapid reevaluation, and (4) appropriate neurosurgical consultation and nursing
      care. Nonoperative treatment may also be considered as a reasonable alternative
      for patients who have severe concurrent medical illness.

PMID- 1978764
TI  - A case of neuroleptic-induced laryngospasm.

PMID- 1978765
TI  - Postanaesthetic nausea in children.
AB  - The incidence of emetic episodes during the first 24 h after anaesthesia was
      studied prospectively in 485 children aged 0-16 years in relation to age,
      premedication, type of induction, type and duration of anaesthesia, type of
      surgery and use of postoperative analgesics. The incidence of emetic episodes was
      25% in the whole material. The majority of the emetic episodes were recorded
      after the immediate recovery period. In children under 2 years of age, vomiting
      was only recorded in 5%. Nausea and vomiting was most common after squint surgery
      (75%) and least common after endoscopies (17%). Neither premedication with
      diazepam nor the method of induction (thiopentone, i.v., thiopentone rectally,
      inhalation with halothane) influenced the incidence of nausea. For the same type
      of surgery, maintenance of anaesthesia with halothane resulted in a lower
      incidence of nausea than anaesthesia with fentanyl-pancuronium.

PMID- 1978766
TI  - Interaction of sevoflurane, isoflurane, enflurane and halothane with non
      depolarizing muscle relaxants and their prejunctional effects at the
      neuromuscular junction.
AB  - The interaction of four inhalational anesthetics (sevoflurane, isoflurane,
      enflurane and halothane) with pancuronium and vecuronium and also their
      prejunctional actions at the neuromuscular junction were quantitatively studied
      using rat phrenic nerve-hemidiaphragm preparations. To investigate the
      prejunctional effects of inhalational anesthetics, a train-of-four ratio (T4/T1)
      and the tetanus ratio (the ratio of the final response to the initial response
      during tetanus) were evaluated. All four inhalational anesthetics markedly
      potentiated the neuromuscular blockade of twitch response caused by either
      pancuronium or vecuronium with halothane and enflurane being the most potent both
      on a % concentration basis and on a MAC (minimum alveolar concentration) basis.
      Although none of the four inhalational anesthetics had any effects on the T4/T1
      ratio, they produced variable effects on the tetanus ratio. Sevoflurane had
      little effect on the tetanus ratio, whereas 1 and 2% isoflurane and 1, 2 and 3%
      enflurane increased the tetanus ratio and 5% halothane and 5% enflurane
      significantly reduced the tetanus ratio. Halothane and enflurane had the most
      potent depressant action of the four inhalational anesthetics both on the %
      concentration basis and on the MAC basis. These results indicate that the main
      site of action of inhalational anesthetics is a postjunctional site at the
      neuromuscular junction and that they do not seem to act on prejunctional sites at
      the concentrations used in clinical situations.

PMID- 1978767
TI  - [Regulation of GH by GHRH: controversies].

PMID- 1978768
TI  - Role of anticholinergics in asthma.

PMID- 1978769
TI  - Effect of procaterol on arterial blood gas in asthmatic children.
AB  - We determined changes in arterial blood gas after the inhalation of procaterol, a
      highly beta 2-selective and long-acting adrenergic agonist, in 11 asthmatic
      children. Seven of the patients, with a maximum fall of 14 mmHg (63.6%), showed a
      decrease in PaO2 (mean +/- SD = -7.1 +/- 4.0 mmHg) and had poorer pulmonary
      function with a lower initial PaO2 than four subjects who had an increase in PaO2
      after inhalation. There was a statistically significant correlation between
      values of the PaO2 before and after inhalation (P less than .05).

PMID- 1978770
TI  - Comparison of cetirizine with astemizole in the treatment of perennial allergic
      rhinitis and study of the concomitant effect on histamine and allergen-induced
      wheal responses.
AB  - Thirty patients suffering from perennial allergic rhinitis took astemizole and
      cetirizine, 10 mg/d, under double-blind, crossover randomized conditions for 4
      weeks. Four weeks washout separated the two periods. Nasal condition was
      improved, histamine and allergen-induced wheal responses were inhibited by both
      treatments with a slight advantage for cetirizine. Both treatments were well
      tolerated.

PMID- 1978771
TI  - Clindamycin vs penicillin for anaerobic lung infections. High rate of penicillin
      failures associated with penicillin-resistant Bacteroides melaninogenicus.
AB  - Thirty-seven adult patients with anaerobic lung infections (27 lung abscesses and
      10 necrotizing pneumonias) were submitted to transthoracic needle-aspiration
      and/or bronchoscopic specimen brush cultures before therapy and thereafter in all
      cases considered to be failures. Patients were randomly assigned to receive
      either clindamycin, 600 mg intravenously every 6 hours, or penicillin G, 2
      million U every 4 hours for no less than 8 days, until clinical and radiological
      improvement became apparent. Treatment was continued orally with clindamycin, 300
      mg every 6 hours, or penicillin V, 750 mg every 6 hours, until completing a
      minimum of 4 weeks. Ten of the 47 anaerobes initially isolated from the lung
      (nine Bacteroides melaninogenicus and one Bacteroides capillosus) were resistant
      to penicillin, but none were resistant to clindamycin. Five of the nine patients
      harboring these penicillin-resistant Bacteroides received penicillin, and all
      failed to respond to therapy. Overall, eight of the 18 patients in the penicillin
      group and one of 19 in the clindamycin group failed to respond to therapy. These
      drugs were equally well tolerated in both groups. The presence of penicillin
      resistant Bacteroides is a frequent cause of penicillin failure in patients with
      anaerobic lung infections. In this setting, clindamycin appears to be the current
      therapy of choice for initial treatment.

PMID- 1978772
TI  - Genetic transformation of glutamine auxotrophy to prototrophy in the
      cyanobacterium Nostoc muscorum.
AB  - Glutamine auxotrophic (Gln-) and L-methionine D,L-sulfoximine (MSX) resistant
      (MSXr) mutants of N. muscorum were isolated and characterized for nitrogen
      nutrition, nitrogenase activity, glutamine synthetase (GS) activity and glutamine
      amide, alpha-keto-glutarate amido transferase (GOGAT) activity. The glutamine
      auxotroph was found to the GOGAT-containing GS-defective, incapable of growth
      with N2 or NH4+ but capable of growth with glutamine as nitrogen source, thus,
      suggesting GS to be the primary enzyme of both ammonia assimilation and glutamine
      formation in the cyanobacterium. The results of transformation and reversion
      studies suggests that glutamine auxotrophy is the result of a mutation in the gln
      A gene and that gln A gene can be transferred from one strain to another by
      transformation.

PMID- 1978773
TI  - The dichotomous distribution of gastrinomas.
AB  - Our experience with 47 sporadic gastrinomas suggests that no less than 85% of
      these tumors are located to the right of the superior mesenteric artery. This
      finding is unexpected because approximately 75% of insulinomas and glucagonomas
      are located to the left of the superior mesenteric artery. All of our
      extrapancreatic gastrinomas have been located to the right. These observations
      prompted us to determine if other extrapancreatic gastrinomas were also
      predominantly located to the right side. We searched the world's literature and
      found 10 cases of ovarian gastrinomas and one case of a renal gastrinoma. Nine of
      these remote extrapancreatic gastrinomas were located on the right side. This
      distribution of remote extrapancreatic gastrinomas is similar to our experience
      with peripancreatic gastrinomas. This unexpected right-sided preponderance of
      both remote and peripancreatic gastrinomas suggests a common origin for both.

PMID- 1978774
TI  - Vitreous amyloidosis associated with homozygosity for the transthyretin
      methionine-30 gene.
AB  - Familial amyloidotic polyneuropathy is an autosomal dominant inherited disorder.
      Biochemical studies have revealed that the amyloid protein in familial
      amyloidotic polyneuropathy of Japanese, Swedish, and Portuguese origin mainly
      consists of a variant transthyretin with one amino acid substitution of
      methionine for valine at position 30, termed TTR met-30. In five Swedish patients
      with familial amyloidotic polyneuropathy we diagnosed homozygosity for the TTR
      met-30 gene using restriction fragment length polymorphism analysis. The
      homozygous individuals did not show more severe systemic symptoms or earlier
      onset than heterozygotes for the TTR met-30 gene. The only clinical difference
      was the presence of vitreous opacities in all homozygous patients.

PMID- 1978775
TI  - Role of elastase and lysyl oxidase activity in spontaneous rupture of internal
      elastic lamina in rats.
AB  - Rupture of the internal elastic lamina may occur spontaneously with age in
      certain arteries of the rat and to various extents in different strains. This
      phenomenon may have some bearing on certain aspects of arterial pathology. For
      this study, we investigated biochemically the mechanisms of formation of
      interruptions in the internal elastic lamina (IIEL) by comparing aortas of Brown
      Norway (BN) rats, which develop numerous IIEL in the abdominal aorta, with those
      of Long-Evans (LE) rats, which develop none. We isolated aortic elastin from BN
      and LE rats and determined its amino acid composition and its susceptibility to
      different elastases. No differences were found between the two strains, but the
      quantity of elastin isolated per aorta was lower in the BN than in the LE rats.
      Elastase-like activity (ELA) of whole aortic extracts, measured with Suc(Ala)3NA
      as a substrate, was greater in the BN rats than in the LE rats of both sexes. The
      assay of ELA in endothelium, media, and adventitia extracted separately showed
      very low levels in the media compared to the endothelium and adventitia. The
      endothelium accounts for about one-half of the total aortic ELA, but a difference
      between the two strains was detected only in the adventitia. With 3H-insoluble
      elastins prepared from BN and LE aortas as substrates, elastinolytic activity
      (EA) was detected only in extracts of endothelium after prior exposure to
      trypsin. Extracts from BN endothelium on BN elastin were more active than were
      those from LE endothelium on LE elastin. The assay of lysyl oxidase activity in
      aortic extracts from the two strains with 3H-collagen from chick embryo calvaria
      as the substrate showed a lower activity in the BN than in the LE rats. Taken
      together, these results suggest that increased elastase activity and decreased
      lysyl oxidase activity may be involved in the formation of IIEL.

PMID- 1978776
TI  - Beta-adrenoceptors and the effect of beta-agonists on protein metabolism in ovine
      primary muscle cultures.
AB  - The beta-adrenergic receptors of differentiated ovine muscle cultures derived
      from either fetal or pre-pubertal lambs were characterized by binding of (+/-)
      [3H]CGP-12177, directly to intact cells in monolayer. Fetal muscle cells
      contained a single class of specific and saturable binding sites which had a
      dissociation constant (Kd) of 0.38 x 10(-9) M and a binding capacity of 55.2
      fmol/micrograms protein. beta-Adrenergic agonists competed for the specific
      binding sites with a typical beta 2-adrenergic specificity. Satellite muscle
      cells derived from pre-pubertal lambs contained two classes of binding site. The
      high affinity site had a Kd of 1.02 x 10(-9) M and a binding capacity of 28.4
      fmol/micrograms protein and the low affinity site a Kd of 12.1 x 10(-9) M and a
      binding capacity of 389 fmol/micrograms protein. beta-Adrenergic agonists
      competed for the specific binding sites with a typical beta 1-adrenergic
      specificity. The beta-agonist cimaterol had no effect on either protein synthesis
      or degradation in fetal muscle cells. In cultures derived from satellite cells
      cimaterol significantly stimulated protein synthesis at concentrations of 10(-8) 
      10(-7) M and at 10(-8) - 10(-6) M in the presence of serum. These effects were
      maintained if 10(-5) M propranolol was added to the incubation media, but were
      blocked by 10(-6) M isoproterenol. Propranolol and isoproterenol had no
      stimulatory effects on protein synthesis. Cimaterol also had no detectable
      effects on protein degradation or the transport of amino acids or glucose. It is
      concluded that although beta-adrenergic receptors are present in ovine muscle
      cultures they may not play a role in the anabolic effect of beta-agonists
      observed in cultured muscle cells.

PMID- 1978777
TI  - Amplification and expression of the c-erb B-2/neu proto-oncogene in human bladder
      cancer.
AB  - The c-erb B-2/neu gene encodes a cell-surface glycoprotein with extensive
      homology to, but distinct from, the epidermal growth-factor receptor. In this
      study, we compared the c-erb B-2/neu gene amplification and expression of tissue
      specimens obtained from the bladders of normal controls and patients with high
      grade transitional cell bladder carcinoma. Southern blot analysis of DNAs from 24
      patients and 5 controls showed 2 cases of c-erb B-2/neu gene amplification in
      patients and none in controls. Western blot analysis demonstrated that c-erb B
      2/neu was expressed in 67.6% (23/34) of patient specimens but in none of the
      controls (0/5). This finding agreed with the result of immunohistochemical
      staining, which showed that tissue from 74.3% (26/35) of the patients and none of
      the controls (0/7) showed positive immunofluorescence staining. This is the first
      report suggesting that c-erb B-2/neu gene amplification may be associated with
      human bladder carcinogenesis.

PMID- 1978778
TI  - Ha-ras oncogene mutations in cell lines derived from rat tracheal implants
      exposed in vivo to 7,12-dimethylbenz[a]anthracene.
AB  - The frequency of Ha-ras mutations was determined as a function of neoplastic
      progression in cell lines derived from rat tracheal implants exposed in vivo to
      7,12-dimethylbenz[a]anthracene. Restriction fragment-length polymorphism (RFLP)
      analysis revealed an A----T transversion in the second base of codon 61 in 2 of
      11 cell lines. One of the positive cell lines was tumorigenic, but the other was
      neither tumorigenic nor anchorage independent, thus indicating a lack of
      correlation between neoplastic stage and ras mutation. Densitometry analysis of
      the RFLP bands indicated that approximately 50% of the cells within these two
      heterogeneous populations contained the mutation. Direct sequence analysis of
      polymerase chain reaction-amplified DNA confirmed these results and did not
      reveal any other mutations in this region of the Ha-ras gene.

PMID- 1978780
TI  - Role of histamine receptors in rabbit pancreatic exocrine secretion stimulated by
      cholecystokinin and secretin.
AB  - An investigation was made of the effects of H1 and H2 receptor agonists and
      antagonists on rabbit pancreatic exocrine secretion stimulated by secretin and
      cholecystokinin (CCK). The H1 agonist 2-thiazolylethylamine elicited dose
      dependent increases in the rate of secretion. Increases in pancreatic juice flow
      and enzyme output were also noted after H2 antagonist cimetidine. In contrast,
      the H1 antagonist chlorpheniramine and H2 agonist dimaprit caused reductions in
      flow and enzyme output. The results suggest that H1 receptors have stimulative
      effects and H2 receptors have inhibitory effects on exocrine rabbit pancreas.

PMID- 1978781
TI  - [Problem of diversity in neural development].

PMID- 1978779
TI  - Excitatory amino acid pathways in brain-stimulation reward.
AB  - A range of agonists and antagonists active at different glutamate/aspartate
      (Glu/Asp) receptor subtypes were injected into rat ventral tegmental (VTA) sites
      downstream from self-stimulation electrodes in the medial forebrain bundle.
      Control injections were made into the contralateral tegmentum. Variable-interval
      (VI 10 s) self-stimulation was not significantly affected by a specific
      antagonist of N-methyl-D-aspartate (NMDA)-type receptors (D,L-2-amino-5
      phosphonovaleric acid (2-AP5), 10 and 50 nmol). Broad-spectrum excitatory amino
      acid (EAA) antagonists viz cis-2,3-piperidine dicarboxylate (cPDA) (10 and 50
      nmol), gamma-D-glutamylaminomethyl sulphonic acid (GAMS) (10 nmol) and p
      chlorobenzoyl-2,3-piperazine dicarboxylic acid (pCB PzDA) (2.0 and 10 nmol),
      active at kainate, quisqualate, as well as NMDA receptors, all produced
      significant depression of responding when injected into the ipsilateral, but not
      the contralateral, tegmentum. Compounds inhibiting Glu/Asp reuptake had variable
      effects: strong depression with dihydrokainic acid (7.5 nmol), or no significant
      effect (L-threo-3-hydroxyaspartic acid, 2.0 and 10 nmol). The receptor agonist,
      NMDA (10 nmol), depressed responding regardless of injection side; kainic and
      responding regardless of injection side; kainic and quisqualic acid elicited
      myoclonic and other non-specific responses in preliminary tests, and were not
      examined further; enhanced responding was not seen. The side-specific blockade of
      responding by non-NMDA antagonists indicates the existence of non-NMDA EAA
      terminals in the VTA, signalling the receipt of hypothalamic brain-stimulation
      reward. Caudally directed EAA projections terminating on A10 dopamine cell bodies
      may account for depression of self-stimulation by EAA antagonists.

PMID- 1978782
TI  - Outgrowth in the nervous system during development and maturity. Proceedings of
      the First Erasmus Winterschool, 5-10 February 1990.

PMID- 1978783
TI  - P-glycoprotein expression in primary breast cancer detected by
      immunocytochemistry with two monoclonal antibodies.
AB  - We have investigated P-glycoprotein (P-gp) expression in samples of primary
      breast cancer from 29 patients before therapy. We employed immunohistochemical
      techniques using two monoclonal antibodies (C219 and MRK16) and an indirect
      alkaline phosphatase method. Heterogeneous expression in epithelial cells was
      detected with both C219 (21 of 29) and MRK16 (16 of 29). A surprising finding was
      P-glycoprotein expression in stromal cells with both C219 (26 of 29) and MRK16
      (12 of 29). Our results suggest that significant levels of P-glycoprotein
      expression may be present in breast cancer before exposure to drugs associated
      with multidrug resistance.

PMID- 1978784
TI  - Expression of c-erbB-2 protein product in bladder cancer.

PMID- 1978785
TI  - Inhibition by neostigmine of hepatocarcinogenesis induced by N-nitrosomorpholine
      in Sprague-Dawley rats.

PMID- 1978786
TI  - Treatment of Alzheimer's disease. Molecular pathology versus neurotransmitter
      based therapy.
AB  - Cortical inhibitory neurotransmitters, neuropeptides, dopamine and noradrenaline
      are probably either not selectively or not critically affected in AD. It is,
      however, likely that a key change is shrinkage or loss of corticocortical
      pyramidal neurones, which probably use glutamate as their transmitter. This
      depletion appears to be circumscribed and clinically relevant.

PMID- 1978787
TI  - Hyperinnervation of orbital frontal cortex in schizophrenia.

PMID- 1978788
TI  - Distribution of catecholamines and of immunoreactivity to substances like
      vertebrate enzymes for the synthesis of catecholamines within the central nervous
      system of the snail, Lymnaea stagnalis.
AB  - Catecholamines (CAs) were detected histochemically within over 185 cell bodies in
      the central nervous system (CNS) of juvenile and young adult Lymnaea. This
      distribution of CA-containing cells in all central ganglia except the pleural
      ganglia is more widespread than previously described but is consistent with other
      reports suggesting numerous roles for CAs within the nervous system. This study
      also describes the distribution of substances which are antigenically similar to
      four bovine enzymes for catecholamine synthesis, but the distribution patterns
      showed little or no overlap with each other or with CA. These results suggest the
      need for caution in the interpretation of such immunohistochemical studies.

PMID- 1978789
TI  - Modulation of tyrosine hydroxylase gene expression in the rat adrenal gland by
      age and reserpine.
AB  - Tyrosine hydroxylase (TH), TH messenger RNA (TH mRNA) and dopamine (DA) were
      measured simultaneously in adrenal glands of individual Fischer 344 rats aged 2,
      6, 13 and 23 months. Between 2 and 23 months TH activity rose 2-fold as compared
      to the youngest group. TH mRNA content of the adrenal gland rose 3-fold between 2
      and 23 months. A 3-fold increase in adrenal DA content, the first catecholamine
      product of TH, provides evidence that the increases in TH gene expression are
      functionally significant. To determine if mechanisms that regulate gene
      expression are altered by aging, the effects of reserpine on induction of TH mRNA
      and TH activity were compared in another group of rats aged 2, 12 and 27 months.
      Consistent with the results of the first experiment, there were age-related
      increases in both TH activity and TH mRNA in the age-matched control groups. TH
      activity rose 2-fold and TH mRNA rose more than 6-fold between 2 and 27 months.
      The discrepancy in the relative magnitudes of increases in TH mRNA and TH protein
      suggest an uncoupling of regulation of TH mRNA and TH protein levels. Moreover,
      there were significant age-related differences with respect to modulation of TH
      gene expression by reserpine treatment. TH activity was induced by reserpine in
      the youngest group, but not in the two older age-groups. In contrast, reserpine
      caused significant induction of TH mRNA in all age groups. These results provide
      evidence that aging is accompanied by alterations in transcriptional and post
      transcriptional mechanisms involved in regulation of TH gene expression.

PMID- 1978790
TI  - NMDA-dependent induction of long-term potentiation in afferent and association
      fiber systems of piriform cortex in vitro.
AB  - Long-term potentiation (LTP) was demonstrated in a slice preparation of piriform
      (olfactory) cortex. LTP could be reliably induced in both afferent and
      association fiber pathways. The magnitude of the observed potentiation was
      greater in the association fiber pathway. 2-Amino-5-phosphonovalerate (APV)
      blocked induction of LTP in both pathways, indicating that N-methyl-D-aspartate
      (NMDA) receptor activation is required for induction.

PMID- 1978791
TI  - A guanine nucleotide-binding protein mediates the inhibition of voltage-dependent
      calcium currents by dopamine in rat lactotrophs.
AB  - The present study examines the effect of dopamine (DA), known to inhibit
      prolactin (PRL) release, on voltage-activated calcium currents in identified rat
      lactotrophs. Two types of voltage-dependent Ca2+ currents were recorded using the
      whole-cell mode of the patch-clamp technique. Both were reversibly inhibited by
      DA application. The inhibitory action of DA was reduced by (i) sulpiride (D2
      antagonist), (ii) preincubation of the cells with pertussis toxin (PTX), and
      (iii) inclusion of guanosine 5'-O-(2-thiodiphosphate) (GDP-beta-S) in the pipette
      solution, whereas it was potentiated by guanosine 5'-O-(3-thiotriphosphate) (GTP
      gamma-S). This DA-induced response could not be overcome by changing the
      adenosine 3',5'-cyclic monophosphate level. These findings suggest that DA can
      inhibit Ca2+ entry through voltage-activated Ca2+ channels via a PTX-sensitive G
      protein(s) pathway thereby affecting PRL release from rat lactotrophs.

PMID- 1978792
TI  - Enhanced survival of cultured dopamine neurons by treatment with soluble extracts
      from chemically deafferentiated striatum of adult rat brain.
AB  - A soluble fraction was extracted from a chemically deafferentiated striatum of
      adult Wistar rats after unilateral lesioning of the nigrostriatal pathway by 6
      hydroxydopamine (6-OHDA) injection. The soluble extract from the lesioned side
      enhanced the survival of cultured mesencephalic dopamine (DA) neurons of 14-day
      old rat embryos as evidenced by quantitative counting of tyrosine hydroxylase
      like immunoreactive cells. The neurotrophic activity of this striatal extract for
      DA neurons was highest 14 days after 6-OHDA injection and became negligible in 28
      days. The extract showed no promoting effects on cultured gamma-aminobutyric acid
      (GABA)-containing mesencephalic neurons. These observations indicate that the
      striatum of adult rats may initiate de novo synthesis of trophic substance(s) for
      DA neurons but not for GABA neurons when subjected to nigral dopaminergic
      deafferentiation.

PMID- 1978793
TI  - Prolactin inhibits the activity of tyrosine hydroxylase in cultured bovine
      adrenal chromaffin cells in a dose-dependent manner.
AB  - Prolactin can modulate the adrenal medulla function, but it has not yet been
      established whether its action is directly exerted on the adrenal medulla cells.
      In this work, we have studied the effect of several concentrations of prolactin
      on the synthesis, storage and release of norepinephrine and epinephrine using
      cultured bovine adrenal chromaffin cells. In these cells, prolactin inhibited the
      activity of tyrosine hydroxylase, the rate-limiting enzyme in the catecholamine
      synthesis, in a dose-dependent manner, from a concentration above 50 ng/ml of
      prolactin in the incubation medium. Surprisingly, this dose-dependent decrease
      was not accompanied by changes in the catecholamine release, since the secretion
      of both norepinephrine and epinephrine as well as the total catecholamine
      secretion were not significantly altered by the different prolactin
      concentrations. Moreover, the cellular content of both catecholamines was not
      altered by prolactin. In summary, these observations allow us to conclude that
      prolactin exerts a direct inhibitory effect on the tyrosine hydroxylase activity
      in cultured adrenal chromaffin cells without altering catecholamine release.

PMID- 1978794
TI  - Characterization of monoamine release in the lateral hypothalamus of awake,
      freely moving rats using in vivo microdialysis.
AB  - Extracellular levels of serotonin (5-HT), dopamine (DA) and their major
      metabolites 5-hydroxyindoleacetic acid (5-HIAA), 3,4-dihydroxyphenylacetic acid
      (DOPAC), and homovanillic acid (HVA), were measured in the lateral hypothalamus
      of awake, freely moving rats using microdialysis combined with HPLC and
      electrochemical detection. To characterize the factors which control 5-HT
      release, the effects of various drugs were assessed. TTX had a reversible
      inhibitory effect on the basal levels of 5-HT, 5-HIAA, DOPAC and HVA. Infusion of
      K+ concomitantly increased 5-HT and DA and decreased 5-HIAA and HVA. Imipramine
      increased extracellular levels of 5-HT and DA and decreased 5-HIAA levels; this
      effect was TTX-sensitive. Systemic pargyline increased extracellular 5-HT and
      markedly decreased the metabolic levels. Pargyline pretreatment in the presence
      of imipramine, infused through the dialysis probe, slowly increased 5-HT levels
      above that produced by the reuptake blocker alone. Infusion with AMPH produced a
      dramatic, TTX-insensitive, increase in 5-HT and DA and a decrease in the
      metabolic levels. These results provide evidence that (1) basal release of 5-HT
      in the lateral hypothalamus results from neuronal activity, (2) the metabolites
      in the extracellular fluid derive primarily from intracellular monoamine oxidase
      (MAO) activity, (3) 5-HT is mainly removed from the extracellular space by a
      reuptake mechanism, with minimal contribution of an extracellular MAO, and (4)
      the AMPH-evoked release of 5-HT and DA is a Na+ channel-independent process.

PMID- 1978795
TI  - Quin2 protects against neuronal cell death due to Ca2+ overload.
AB  - Quin2-acetoxymethylester (quin2/AM) (50 microM), administered directly to the
      motoneuronal pool of the frog spinal cord, could be loaded into the motoneuron as
      well as the other cells in the lumbar region. Depolarizing responses of the
      ventral root to L-glutamate in the quin2-loaded side persisted even after
      prolonged exposure to A23187 (2.0 microM), while the responses in the unloaded
      side were markedly reduced. Histologically confirmed neuronal cell loss from the
      motoneuronal pool induced by A23187 (2.0 microM) or by a high concentration of L
      glutamate (10 mM) was prevented by pretreatment with quin2/AM. A23187- and L
      glutamate-induced histological and functional damage in neuronal cells and the
      protective effects of quin2 on them provide further evidence for cell death due
      to Ca2+ overloading.

PMID- 1978796
TI  - Organization of tyrosine hydroxylase- and serotonin-immunoreactive brainstem
      neurons with axon collaterals to the periaqueductal gray and the spinal cord in
      the rat.
AB  - Retrograde tracing and immunocytochemistry were used to examine the axon
      collateralization of brainstem serotonin (5-HT) and norepinephrine (NE) cells to
      the periaqueductal gray (PAG) and spinal cord. Tyrosine hydroxylase (TH)
      immunofluorescent neurons which collateralize to the PAG and the cervical spinal
      cord were found in all brainstem catecholamine cell groups previously shown to
      contain neurons which project to the spinal cord, including the A5 and A7 cell
      groups, locus coeruleus, subcoeruleus and the C1 cell group. Many TH
      immunofluorescent cells which project to the PAG but not to the spinal cord were
      also found. The region of the nucleus raphe magnus (NRM) also contained many
      neurons retrogradely labeled from the PAG. These overlapped with the distribution
      of spinally projecting 5-HT-immunofluorescent cells in the NRM, however, less
      than 1% of the PAG projecting cells in this region were 5-HT-immunofluorescent.
      In contrast, many 5-HT-immunofluorescent cells in the more rostral nucleus raphe
      pontis and nucleus raphe dorsalis were retrogradely labeled from the PAG but not
      from the spinal cord. Finally, a population of neurons in the NRM and adjacent
      reticular formation and in the region of several pontomedullary catecholamine
      cell groups collateralized to the PAG and spinal cord, but were neither 5-HT nor
      TH-immunofluorescent. Taken together, these findings raise the possibility that
      the noradrenergic contribution to the spinal antinociceptive effects produced by
      PAG electrical stimulation results, in part, from antidromic activation of
      brainstem noradrenergic neurons that have axon collaterals projecting to the PAG
      and spinal cord. In contrast, the 5-HT contribution to the spinal antinociceptive
      effects produced by PAG electrical stimulation is more likely to derive, as
      previously proposed, from orthodromic activation of raphe-spinal serotonergic
      axons.

PMID- 1978797
TI  - Progestin receptors in the ventromedial nucleus of the hypothalamus and arcuate
      nucleus-median eminence are decreased by idazoxan.
AB  - Steroid-dependent lordosis behavior in ovariectomized (OVX) guinea pigs is
      attenuated by alpha 1- and/or alpha 2-noradrenergic (NE) receptor antagonists.
      Correlated with the decrease in lordosis after alpha 1-NE receptor blockade by
      prazosin is a decrease in 'cytosol' progestin receptors in the ventromedial
      hypothalamic nucleus (VMN). We examined whether a presumed alpha 2-NE receptor
      blocker (idazoxan, IDA) also affects progestin receptors. A decrease in 'cytosol'
      progestin receptors was found after IDA treatment of OVX, estrogen-treated guinea
      pigs in the VMN and the arcuate nucleus-median eminence (ARC-ME). Apparently,
      either prazosin or IDA can inhibit lordosis behavior and decrease 'cytosol'
      progestin receptors in the VMN. In contrast, idazoxan but not prazosin, decrease
      'cytosol' progestin receptors in the ARC-ME.

PMID- 1978798
TI  - Polymorphism in polydnavirus genomes.
AB  - Polymorphisms were readily detected in polydnavirus DNA extracted from several
      different species belonging to two different families of parasitic hymenoptera.
      Heterogeneity was observed as differences in electrophoretic profiles of genome
      segments, differences in the number of cross-hybridizing genome segments, and
      restriction fragment length polymorphisms; polymorphism was also detected at the
      level of an individual genome segment. Some implications drawn from these
      observations are discussed.

PMID- 1978799
TI  - Modulation by estrogen of the incidence of diethylnitrosamine-induced gamma
      glutamyltranspeptidase-positive foci in rat liver.
AB  - We measured the number and size of foci of altered hepatocytes induced after 8
      weeks by diethylnitrosamine (DENA) in the liver of rats pretreated with 17 beta
      estradiol (E2), 1 or 24 h prior to the administration of the carcinogen. The
      average size of the lesions was the same in the E2 pretreated and unpretreated
      animals. The number of gamma-glutamyltranspeptidase (GGT)-positive foci per cm3
      of liver increased from 364 +/- 57 in unpretreated animals to 1149 +/- 186 in
      animals receiving E2 24 h before DENA; it raised to 3779 +/- 280 when the hormone
      was injected 1 h before the carcinogen, i.e. about 25% of the number of foci
      scored in rats receiving the carcinogen 24 h after partial hepatectomy. The
      hypothesis is proposed that 1-h pretreatment with E2 increases hepatocyte
      susceptibility towards DENA action by enhancing the accessibility of the genome
      to the carcinogen.

PMID- 1978800
TI  - Distribution of FMRFamide-like immunoreactivity in the brain, retina and nervus
      terminalis of the sockeye salmon parr, Oncorhynchus nerka.
AB  - Neurons displaying FMRFamide(Phe - Met - Arg - Phe - NH2)-like immunoreactivity
      have recently been implicated in neural plasticity in salmon. We now extend these
      findings by describing the extent of the FMRF-like immunoreactive (FMRF-IR)
      system in the brain, retina and olfactory system of sockeye salmon parr using the
      indirect peroxidase anti-peroxidase technique. FMRF-IR perikarya were found in
      the periventricular hypothalamus, mesencephalic laminar nucleus, nucleus nervi
      terminalis and retina (presumed amacrine cells), and along the olfactory nerves.
      FMRF-IR fibers were distributed throughout the brain with highest densities in
      the ventral area of the telencephalon, in the medial forebrain bundle, and at the
      borders between layers III/IV and IV/V in the optic tectum. High densities of
      immunoreactive fibers were also observed in the area around the torus
      semicircularis, in the medial hypothalamus, median raphe, ventromedial tegmentum,
      and central gray. In the retina, immunopositive fibers were localized to the
      inner plexiform layer, but several fiber elements were also found in the outer
      plexiform layer. The olfactory system displayed FMRF-IR fibers in the epithelium
      and along the olfactory nerves. These findings differ from those reported in
      other species as follows: (i) FMRF-IR cells in the retina have not previously
      been reported in teleosts; (ii) the presence of FMRF-IR fibers in the outer
      plexiform layer of the retina is a new finding for any species; (iii) the
      occurrence of immunopositive cells in the mesencephalic laminar nucleus has to
      our knowledge not been demonstrated previously.

PMID- 1978801
TI  - Lateral diffusion of luminal membrane components during secretion in parotid
      acinar cells of the rat. Immunocytochemical and freeze-fracture studies.
AB  - The movements of the molecular components of the luminal plasma membrane during
      exocytotic secretion in parotid acinar cells were examined. For
      immunocytochemical study, we used an antiserum of dipeptidyl peptidase IV as a
      marker for the components of the luminal plasma membrane of acinar cells. In
      unstimulated acinar cells, dipeptidyl peptidase IV immunoreactivity is restricted
      to the luminal plasma membrane. However, after secretion was stimulated with a
      beta-adrenergic agonist, isoproterenol, immunostaining became detectable on the
      membrane of discharged granules. Freeze-fracture images showed that the density
      of intra-membrane particles on the P-fracture leaflets of discharged granule
      membranes is much higher than that of undischarged granule membranes during
      secretion. These results suggest that in parotid acinar cells of the rat, the
      components of the luminal plasma membrane move laterally, during secretion, to
      the membranes of discharged granules.

PMID- 1978802
TI  - Ultrastructural distribution of somatostatin-14 and -28 in rat adrenal cells.
AB  - Previous studies have shown that somatostatin modulates angiotensin-induced
      aldosterone secretion by adrenal glomerulosa cells. This effect is mediated
      through specific receptors which do not show any preference for somatostatin-14
      (S14) or the N-extended form somatostatin-28 (S28). The study of the distribution
      of 125I-Tyr [Tyr0, DTrp8] S14- and 125I-Tyr [Leu8, DTrp22, Tyr25] S28-binding in
      frozen sections of the rat adrenal by autoradiography indicated that both
      peptides bind to similar loci. High concentrations of binding sites were observed
      in the zona glomerulosa, and low concentrations were detected in the medulla. At
      the ultrastructural level, immunocytochemistry after cryoultramicrotomy revealed
      endogenous S14- and S28-like immunoreactive material in zona glomerulosa and in
      medulla. In glomerulosa cells, immunoreactive material was localized at the
      plasma membrane level, in the cytoplasmic matrix, in the mitochondria, and in the
      nucleus. S14- and S28-like materials were detected in both epinephrine and
      norepinephrine-storing cells of the adrenal medulla. In these cells, the
      distribution of either immunoreactive product was similar; it was observed in
      cytoplasmic matrix, secretory granules and nucleus, but not at the plasma
      membrane level. In situ hybridization does not reveal somatostatin mRNA in zona
      glomerulosa or medulla. These results demonstrate that S14 and S28 bind to, and
      are taken up by zona glomerulosa and adrenal medullary cells, but are not
      produced by these cells.

PMID- 1978804
TI  - The central serotoninergic system.

PMID- 1978805
TI  - [Tardive dyskinesia in long-term treatment with neuroleptics--review of the
      literature and personal experience with its therapy].

PMID- 1978803
TI  - Catecholamines and catecholamine-synthesizing enzymes in guinea-pig sensory
      ganglia.
AB  - Cranial and spinal sensory ganglia of the guinea-pig were investigated by means
      of histochemistry and biochemistry for the presence of catecholamines and
      catecholamine-synthesizing enzymes. Sensory neurons exhibiting immunoreactivity
      to the rate-limiting enzyme of catecholamine synthesis, tyrosine hydroxylase
      (TH), were detected by immunohistochemistry in lumbo-sacral dorsal root ganglia,
      the nodose ganglion and the petrosal/jugular ganglion complex. The carotid body
      was identified as a target of TH-like-immunoreactive (TH-LI) neurons by the use
      of combined retrograde tracing and immunohistochemistry. Double-labelling
      immunofluorescence revealed that most TH-LI neurons also contained somatostatin
      LI, but TH-LI did not coexist with either calcitonin gene-related peptide- or
      substance P-LI. TH-LI neurons did not react with antibodies to other enzymes
      involved in catecholamine synthesis, i.e., aromatic amino acid decarboxylase
      (AADC), dopamine-beta-hydroxylase (D beta H), and phenylethanolamine-N-methyl
      transferase (PNMT). Petrosal neurons as well as their endings in the carotid body
      lacked dopamine- and L-DOPA-LI. Sensory neurons did not display glyoxylic acid
      induced catecholamine fluorescence. Ganglia containing TH-LI neurons were kept in
      short-term organ culture after crushing their roots and the exiting nerve in
      order to enrich intra-axonal transmitter content at the ganglionic side of the
      crush. However, even under these conditions, catecholamine fluorescence was not
      detected in axons projecting peripherally or centrally from the ganglia.
      Sympathetic noradrenergic nerves entered the ganglia and terminated within them.
      Accordingly, biochemical analyses of guinea-pig sensory ganglia revealed
      noradrenaline but no dopamine. In conclusion, catecholamines within guinea-pig
      sensory ganglia are confined to sympathetic nerves, which fulfill presently
      unknown functions. The TH-LI neurons themselves, however, lack any additional
      sign of catecholamine synthesis, and the presence of enzymatically active TH
      within these neurons is questionable.

PMID- 1978807
TI  - Brain natriuretic peptide-like immunoreactive innervation of the cardiovascular
      and cerebrovascular systems in the rat.
AB  - Atrial natriuretic peptide is a potent dilator of aorta and renal and cerebral
      arteries and inhibits sympathetic tone in the heart in several mammalian species.
      We examined the possibility that a molecule related to porcine brain natriuretic
      peptide (pBNP), which acts at the same receptor sites as atrial natriuretic
      peptide, might provide an alternative source of natriuretic peptide to the
      cardiovascular system in the rat. An antiserum against pBNP demonstrated profuse
      immunoreactive innervation of the heart, cerebrovascular tree, and renal
      arteries. pBNP-like immunoreactive fibers ran in bundles along the surface of the
      heart, innervating the atria most heavily and penetrating the ventricular
      myocardium along the coronary arteries. There was greater density of innervation
      of the right side of the heart compared with the left, particularly in the
      ventricles, suggesting a parasympathetic origin. The entire cerebrovascular tree
      was innervated by immunoreactive pBNP fibers, with the densest concentration of
      immunoreactive fibers along the surface of the internal carotid, middle cerebral,
      posterior communicating, and anterior cerebral arteries. The proximal renal
      arteries were not innervated, but as they approached the kidney, they were
      invested by bundles of immunoreactive pBNP fibers. These axons followed the major
      branches of the renal artery into the kidney parenchyma, running along the
      surface of the arterioles up to their entrance into the renal glomeruli. No
      immunoreactive innervation of the aorta or proximal brachiocephalic, subclavian,
      or carotid arteries was seen. A substance related to pBNP may serve as a
      neuromodulator regulating cardiac output as well as blood flow in certain
      vascular beds.

PMID- 1978806
TI  - [An essay on attention].

PMID- 1978808
TI  - Beta-adrenergic agonists stimulate the oxidative pentose phosphate pathway in the
      rat heart.
AB  - The oxidative pentose phosphate pathway is poorly developed in the rat heart
      compared with other organs, since the activity of glucose-6-phosphate
      dehydrogenase (G-6-PDH), the first and rate-limiting enzyme of the oxidative
      pentose phosphate pathway, is low. As a consequence, the available pool of 5
      phosphoribosyl-1-pyrophosphate and the rate of adenine nucleotide biosynthesis
      are limited. Isoproterenol, 24 hours after subcutaneous administration at 0.1, 1,
      and 25 mg/kg, stimulated the activity of G-6-PDH in whole hearts dose-dependently
      from 4.3 +/- 0.16 (control) to 6.6 +/- 0.35, 10.3 +/- 0.82, and 11.5 +/- 0.56
      units/g protein, respectively. The activity of 6-phosphogluconate dehydrogenase,
      another of the enzymes in the oxidative pentose phosphate pathway, remained
      unchanged. G-6-PDH activity started to increase 12 hours after isoproterenol
      application, when the glycogenolytic and functional response was over, and
      reached a peak value between 24 and 48 hours. This stimulating effect was also
      demonstrated in cardiac myocytes that were isolated 28 hours after isoproterenol
      application. beta-receptor blockade with atenolol reduced the isoproterenol
      induced increase in cardiac G-6-PDH activity by 90%. Cycloheximide, which
      inhibits translation, and actinomycin D, which interferes with transcription,
      attenuated it by 83% and 78%, respectively. These results indicate that cardiac
      beta-adrenergic receptors and enzyme protein synthesis are involved in this
      effect. Other beta-sympathomimetic agents such as dopamine, dobutamine,
      fenoterol, salbutamol, and terbutaline also stimulated myocardial G-6-PDH
      activity in a time- and dose-related manner. The calcium antagonist D 600
      (gallopamil) reduced the isoproterenol-elicited stimulation by 65%, and verapamil
      blunted the fenoterol-induced increase by 50%. This suggests that Ca2+ ions also
      contribute to the stimulation of the cardiac oxidative pentose phosphate pathway.

PMID- 1978810
TI  - Clonal analysis of T cell infiltrates in synovial tissue of patients with
      rheumatoid arthritis.
AB  - To investigate the possibility of the presence of disease-relevant, antigen
      specific immune reactions in rheumatoid arthritis (RA), clonal diversity of the T
      cells in the synovial tissue was examined. T cells were directly cloned by in
      vitro stimulation with phytohemagglutin and interleukin 2 from both the
      peripheral blood and inflammatory synovial tissue. Their clonotypes were defined
      by analyzing rearrangement patterns of T cell receptor (TCR) beta and gamma chain
      genes using Southern blotting. In total, 111 clones from the synovial tissue
      (four patients) and 45 from the peripheral blood (one patient) were studied.
      Although most of the clones were unique in their TCR gene rearrangement patterns,
      2 clones from the synovial tissue of one patient had identical patterns. These 2
      clones were CD3+, 4-, 8+. Since phenotypic analysis of 82 clones from the
      synovial tissues revealed that CD8+ T cell clones were less frequent (24%) than
      CD4+ clones, the clonal identity observed here in 2 clones may not be negligible.
      Furthermore, 1 CD8+ clone from the peripheral blood of the same patient also had
      the same clonotype. These results may suggest selective trafficking or
      proliferation of CD4-, CD8+ T cells in RA synovial tissue.

PMID- 1978809
TI  - Ductal lesions of exocrine glands and insulitis induced by L3T4+ T cells
      following graft-versus-host reaction due to major histocompatibility complex
      class II disparity.
AB  - Recently, we have demonstrated characteristic hepatic lesions resembling primary
      biliary cirrhosis (PBC) in semiallogeneic F1 hybrid mice with major
      histocompatibility complex (MHC) class II-disparate graft-versus-host reaction
      (GVHR). In the present study, we tried to reveal other ductal lesions in
      extrahepatic organs, including salivary glands and pancreas. Murine strains used
      are C57BL/6 (B6), B6 mutant bm1, and bm12. bm1 carries a mutant gene at the H-2K
      locus of MHC and bm12 carries a mutant gene at the I-A locus of MHC of the B6
      strain. The (B6 x bm1)F1, (B6 x bm12)F1, and (bm1 x bm12)F1 mice were injected
      intravenously with 1 x 10(7) B6 L3T4+ or Lyt-2+ T cells and were sacrificed on
      the 14th day postinjection for histological examinations. Mononuclear cell
      infiltration was detected around the ducts of salivary glands only in (B6 x
      bm12)F1 mice injected with B6 L3T4+ T cells. A moderate to marked level of cell
      infiltration was demonstrated in pancreas of (B6 x bm12)F1 recipients similar to
      nonobese diabetic (NOD) mice. By immunohistochemical examinations, infiltrating
      cells were shown to consist not only of L3T4+ but also of Lyt-2+ T cells, even
      after the inoculation of L3T4+ cells. These results are discussed in reference to
      mechanisms of organ-specific autoimmune diseases, especially insulitis in NOD
      mice which show insulin-dependent diabetes mellitus.

PMID- 1978811
TI  - First Breton Workshop on Autoimmunity. Proceedings of a symposium. Brest, France,
      March 8-10, 1990.

PMID- 1978812
TI  - Aneurysmal form of aortoarteritis (Takayasu's disease): analysis of thirty cases.
AB  - The clinical and radiological features, and outcome of 30 patients including 22
      females, with the aneurysmal form of aortoarteritis were analysed. The average
      age at diagnosis was 27.4 +/- 7.2 years. Features which indicated the diagnosis
      of aneurysmal aortoarteritis included young age, female sex, characteristic
      location, associated stenotic lesions and the presence of multiple aneurysms.
      There were 41 fusiform and 18 saccular aneurysms, mostly located in the
      descending aorta. Diffuse dilatation (n = 24) was seen mainly in the ascending
      aorta. Two patients had dissecting aneurysms, while one patient had an aneurysm
      of the left main coronary artery. Both these lesions are rare in aortoarteritis.
      The aneurysmal form was associated with a higher incidence of aortic incompetence
      (P less than 0.01) and elevated ESR (P less than 0.001) as compared to the more
      common non-aneurysmal form. The average follow-up period was 59.7 (+/- 48.1)
      months. The event-free survival rate was 82.9% at 5 years, similar to that seen
      in the non-aneurysmal form. These data should be useful to the clinician in the
      diagnosis and management of the aneurysmal form of aortoarteritis.

PMID- 1978813
TI  - Atrial natriuretic peptide in lymphoid organs of various species.
AB  - 1. Evidence for the occurrence of atrial natriuretic peptide (ANP) in various
      lymphoid organs of different species (rat, mouse, pig, chicken) is provided. 2.
      ANP precursor material (1-126) as well the physiologically active ANP (99-126),
      were identified by chromatographic analysis and RIA in extracts of thymus, spleen
      and lymph nodes of rat, mouse and pig. 3. mRNA coding for ANP was demonstrated
      both in the thymus and in isolated thymocytes of these species. Furthermore, mRNA
      for ANP was detected in spleen and lymph nodes (rat and pig). 4. The bursa of
      Fabricius, thymus glands and spleen of chickens were also shown to express mRNA
      coding for ANP. 5. These findings provide a firm basis for a link of ANP to the
      immune system, a novel aspect of possible biological functions of this peptide.

PMID- 1978814
TI  - Calcium transport activities of plasma membranes isolated from the livers of
      various animal species.
AB  - 1. Plasma membranes of comparable yield and purity were isolated from the livers
      of various animal species belonging to phylogenetic groups from Amphibia to
      Mammalia. 2. Calcium transport activity was observed in all liver plasma
      membranes examined. 3. No phylogenetic pattern of expression of the liver plasma
      membrane calcium transport system was observed, with the order of activity being:
      guinea pig greater than rabbit greater than frog greater than chicken = hamster
      greater than rat = budgerigar = turtle greater than beef cattle greater than
      mouse = duck. 4. Calcium transport activity was only 9.7 and 8.7% of adult frog
      levels in plasma membranes isolated from the livers of tadpoles without and with
      limbs, respectively. 5. Liver plasma membrane calcium transport activity was 25%
      higher in adult chickens than in day-old chicks. 6. A possible role for thyroid
      hormone in the development of the liver plasma membrane calcium transport system
      is discussed.

PMID- 1978816
TI  - Effect of albumin on oleic acid lymphatic absorption in rats.
AB  - 1. The aim of this study was to investigate how fatty acid absorption was
      affected when exogenous fatty acids were complexed with albumin in absence of
      bile. Experiments were carried out in vivo, in order to study overall absorption
      processes. 2. An equimolar mixture of 14C oleic acid, palmitic acid and
      monopalmitin was infused intraduodenally in bile- and pancreatic juice-diverted
      rats. 3. Lipids were emulsified with either sodium taurocholate or fatty acids
      complexed with albumin. 4. Lymphatic lipid output was compared during the 6 hr
      following infusion of 90 mumol of the radioactive lipid mixture. 5. Lymphatic
      radioactive lipid recovery was significantly decreased by albumin. 6. Only 17% of
      the infused radioactivity was recovered in lymph when fatty acids were complexed
      with albumin against 37% when lipids were emulsified with sodium taurocholate. 7.
      Unrecovered lymph radioactivity was found at the distal part of intestine.
      Moreover, albumin significantly decreased lymph flow. 8. We conclude that
      undigested albumin acted at the luminal level of lipid absorption processes and
      specifically decreased fatty acid uptake.

PMID- 1978815
TI  - Effects of electrical stimulation on the activity of hexokinase in the medial
      gastrocnemius muscle of aged rats after hindlimb suspension.
AB  - 1. The activity of the enzyme Hexokinase (E.C. 2.7.1.1.) has been measured after
      a 21 day period of hindlimb suspension and a 14 day period of recovery with or
      without electrical stimulation in the old rat Medial Gastrocnemius muscle divided
      in its white and red parts. 2. After suspension, the activity of the enzyme
      increased in both parts of the muscle and returned near its control value more
      rapidly in the red part of the muscle when electrical stimulation was applied.

PMID- 1978817
TI  - Brown adipose tissue lipid is the main source of energy during arousal of the
      golden hamster (Mesocricetus auratus).
AB  - 1. Male golden hamsters were induced to hibernate. 2. During stimulated arousal
      (i) the time course of increase in deep body temperature was related to the time
      course of increasing oxygen consumption and (ii) brown adipose tissue lipid
      content was determined at several time points. 3. In early arousal (0-30 min)
      more lipid was mobilised (14.6 kJ) than was utilised in metabolism (3.5 kJ). BAT
      lipids accounted for 88% of the total energy requirement of arousal (90 min). 4.
      We conclude that BAT not only supplies heat for arousal but fuel for other
      arousing tissues.

PMID- 1978818
TI  - C-reactive protein in rat: in development, pregnancy and effect of sex hormones.
AB  - 1. In Wistar strain rats, the serum concentration of C-reactive protein (CRP) was
      3.6 +/- 0.8 micrograms/ml at the birth and no apparent change was observed during
      15 days after delivery. 2. Thereafter it increased about 30 times rapidly until
      day 30 and then rather gradually reaching the adult level of 0.4-0.8 mg/ml. 3.
      Before delivery, there were two peaks in the CRP level, on day 0 and day 15 of
      gestation. The concentrations were 0.70 +/- 0.06 and 0.77 +/- 0.10 mg/ml,
      respectively. 4. The CRP level decreased to 0.42 +/- 0.05 mg/ml at the delivery
      and increased to 0.54 +/- 0.05 mg/ml within 2 days after delivery. 5. The
      treatment with estradiol-17 beta resulted in the decrease of CRP (52%) in both
      ovariectomized and non-treated female rats. 6. The treatment with testosterone
      resulted in the increase of CRP in male but not in female rats. 7. However, in
      ovariectomized rats, testosterone elevated the serum CRP. 8. In neither
      ovariectomized nor intact female rats, progesterone and corticosterone showed any
      remarkable effect.

PMID- 1978819
TI  - Binding properties of duodenal 1,25-dihydroxyvitamin D3 receptors as affected by
      phosphorus depletion in lactating goats.
AB  - 1. Capacity and affinity of duodenal 1,25(OH)2D3 receptors were measured in P
      depleted goats and in control animals kept on an adequate P supply. Plasma
      concentrations of Pi, Ca and vitamin D3 metabolites and activity of plasma
      alkaline phosphatase were measured to characterize the effects of P depletion. 2.
      During P depletion plasma Pi concentrations decreased significantly whereas
      plasma Ca and alkaline phosphatase activity increased. No changes were recorded
      for plasma vitamin D3, 25OHD3 and 1,25(OH)2D3 concentrations. 3. P depletion
      resulted in a significant decrease of the equilibrium dissociation constant Kd of
      duodenal 1,25(OH)2D3 receptors without affecting the maximum binding capacity.

PMID- 1978820
TI  - Resonant frequency of the chest-lung system by analysis of the respiratory flow
      curve.
AB  - 1. Resonant frequency of the chest-lung system in six tracheotomized,
      spontaneously breathing dogs was determined by analyzing the shape of the
      respiratory flow curve. 2. The resonant frequency was calculated from the
      periodic deviations from a sinusoidal flow pattern observed in the inspiratory
      phase of the breathing cycle. 3. Mean (+/- S.D.) resonant frequency was 6.1 +/-
      0.9 Hz which was very close to the panting frequency (5.7 Hz) of the same dogs.
      4. Resonant frequencies of the respiratory system in various species are
      compared.

PMID- 1978821
TI  - Insulin-stimulated glucose transport regulated by adenylate cyclase system in rat
      adipocytes.
AB  - 1. In rat adipocytes, there was an inverse correlation between insulin-stimulated
      2-deoxyglucose (2-DG) uptake and cAMP levels, indicating that cAMP suppressed the
      2-DG uptake stimulated by insulin. 2. This inhibitory effect of cAMP was due to
      suppression of translocation of glucose transporters rather than that of insulin
      binding to its receptors. 3. Phosphodiesterase inhibitors (IBMX, Ro 20-1724, and
      cilostamide) inhibited the 2-DG uptake, which was brought about by direct
      interaction with glucose transporters in the plasma membranes.

PMID- 1978822
TI  - Plasma lipoprotein profiles in broiler chicks (Gallus domesticus): effects of
      early overfeeding.
AB  - 1. Twenty-eight day old broiler chicks gavage fed for 22 days consumed 40% more
      feed and gained 100-110 g more than control birds. 2. Normal feeding resumed on
      day 41, by day 63 feed intakes and body weights of overfed and control birds were
      equal. 3. Moderate differences in lipid compositions of LDL and VLDL were
      observed at 41 and 50 but not at 63 days. 4. In contrast to mammals where early
      over feeding predisposes to adult obesity, lipoprotein profiles and ad lib
      feeding patterns of chicks are not readily altered by dietary measures.

PMID- 1978823
TI  - The integration of receptor-regulated intracellular calcium release and calcium
      entry across the plasma membrane.

PMID- 1978824
TI  - The role of calcium in neurotransmitter release: existing models and new
      approaches to evaluate possible mechanisms.

PMID- 1978825
TI  - Pulmonary function and alcohol consumption.

PMID- 1978826
TI  - Allelic variants at insulin-receptor and insulin gene loci and susceptibility to
      NIDDM in Welsh population.
AB  - A cohort of 132 well-documented White Welsh non-insulin-dependent diabetic
      (NIDDM) subjects were genotyped for 5 restriction-fragment-length polymorphisms
      (RFLPs) at the insulin-receptor gene (IRG) locus and a polymorphic locus 5' to
      the insulin gene. There was no significant difference in RFLP frequencies between
      the NIDDM subjects and a group of 87 matched White control subjects. Paired
      haplotype analysis of the IRG RFLPs suggested a difference between NIDDM and
      control groups for the endonuclease combinations Bgl II-Rsa I and Bgl II-Xba I.
      Analysis of implied haplotypes defined by the endonucleases Bgl II, Rsa I, and
      Xba I revealed one haplotype to be more prevalent in the NIDDM group; whereas,
      another haplotype was associated with the control group (P less than 0.02).
      Subset analysis within the NIDDM cohort compared the metabolic response of NIDDM
      subjects with the differing IRG haplotypes to a standard meal tolerance test.
      Both groups showed equivalent basal and postprandial glucose excursions, but one
      group revealed a significantly exaggerated plasma insulin response compared with
      the other (P less than 0.05). This may reflect the influence of genetic variation
      at the IRG locus on insulin sensitivity in patients with NIDDM.

PMID- 1978827
TI  - Multigenic basis for type I diabetes. Association of HRAS1 polymorphism with HLA
      DR3, DQw2/DR4, DQw8.
AB  - We analyzed extended haplotypes composed of DNA loci on the short arm of
      chromosome 11 for segregation with insulin-dependent (type I) diabetes mellitus.
      The markers for these loci are tyrosine hydroxylase, insulin, and c-Ha-ras-1
      proto-oncogene (HRAS1). We report, in a study of 27 families, that a specific
      haplotype (H), containing a 3-kilobase (kb) HRAS1-Taq I DNA polymorphism,
      segregated differentially in diabetic and nondiabetic siblings (P = 0.005). A
      parallel population study showed that the 3-kb HRAS1-Taq I polymorphism is
      increased in frequency in type I patients having two strong HLA-susceptibility
      haplotypes compared with other type I patients or healthy control blood donors (P
      less than 0.010 and P less than 0.025, respectively). The polymorphic variable,
      enhancer, and promoter regions flanking the human insulin gene on the H haplotype
      were not associated with type I diabetes. These results indicate that the HRAS1
      locus or genes in linkage disequilibrium with this locus are involved in the
      pathogenesis of HLA-DR3/4 type I diabetes mellitus.

PMID- 1978828
TI  - Polymorphisms of GLUT2 and GLUT4 genes. Use in evaluation of genetic
      susceptibility to NIDDM in blacks.
AB  - The liver/islet (GLUT2) and muscle/adipose tissue (GLUT4) glucose-transporter
      gene products, membrane proteins that facilitate glucose uptake into cells, are
      important molecules for normal carbohydrate metabolism. Recent isolation of the
      genes encoding these proteins provides a means to assess the role of possible
      defects that might contribute to impaired glucose-stimulated insulin secretion or
      impaired insulin-mediated glucose uptake, both prominent phenotypic features of
      non-insulin-dependent diabetes (NIDDM). A GLUT2 cDNA clone was isolated from a
      human liver cDNA library to search for polymorphisms at this locus in American
      Blacks. Three highly polymorphic sites were identified, one of which (EcoRI-Hae
      III) appears to be due to an insertion and/or deletion of 200 base pairs of DNA.
      Significant linkage disequilibrium between these sites over approximately 30
      kilobases of genomic DNA suggested that these polymorphisms could be in linkage
      disequilibrium with mutations at this locus if they exist. A GLUT4 cDNA clone was
      also utilized to search for polymorphisms at this locus, but only one previously
      described polymorphism was observed. GLUT2 and GLUT4 cDNA probes were used to
      evaluate DNA polymorphisms in genomic DNA from American Blacks with NIDDM. The
      allelic, genotypic, and haplotypic frequencies of the DNA polymorphisms at these
      loci did not differ from the frequencies in nondiabetic subjects. Because no
      associations with NIDDM were found, it appears unlikely that mutations at these
      loci contribute in a major way to the genetic susceptibility to NIDDM observed in
      American Blacks.

PMID- 1978829
TI  - Tumor necrosis factor-increased hepatic very-low-density lipoprotein production
      and increased serum triglyceride levels in diabetic rats.
AB  - Previous studies demonstrated that administration of tumor necrosis factor (TNF)
      to diabetic rats rapidly increases serum triglyceride levels and stimulates
      hepatic lipogenesis without affecting the activity of adipose tissue lipoprotein
      lipase or serum insulin levels. The purpose of this study was to determine the
      mechanism by which TNF increases serum triglyceride levels and stimulates hepatic
      fatty acid synthesis in diabetic animals. The maximal increase (approximately 2
      fold) in serum triglyceride levels in diabetic rats is seen with a dose of 10
      micrograms TNF/200 g body wt, and the half-maximal effect is observed with 5
      micrograms TNF/200 g body wt. The clearance of labeled triglyceride-rich
      lipoproteins from the circulation is not affected by TNF administration
      (triglyceride t 1/2; diabetic vs. TNF-administered diabetic, 3.5 +/- 0.7 vs. 4.0
      +/- 0.6 min, respectively; NS). The production of triglyceride, measured by the
      Triton WR-1339 technique, is increased twofold in diabetic animals after TNF
      administration. These results indicate that the rapid increase in serum
      triglyceride levels after TNF treatment is accounted for by increased hepatic
      lipoprotein secretion. TNF administration did not alter either the amount or
      activation state of hepatic acetyl-CoA carboxylase, a key regulatory enzyme in
      fatty acid synthesis. There was also no change in the hepatic levels of fatty
      acyl-CoA, an allosteric inhibitor of acetyl-CoA carboxylase. However, there was a
      71% increase in hepatic citrate concentrations. Citrate is an allosteric
      activator of acetyl-CoA carboxylase, and changes in hepatic citrate
      concentrations have been shown to mediate changes in the rates of fatty acid
      synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1978830
TI  - Clinical implications of growth hormone feedback mechanisms.
AB  - It is now clear that both long-loop and ultrashort-loop feedback mechanisms may
      operate to autoregulate GH secretion at both central nervous system and pituitary
      levels. The key components of this control mechanisms involve GH itself, the GH
      dependent peptides, somatomedins, and the two specific hypothalamic
      hypophysiotropic peptides GHRH and somatostatin. Presently, the intimate
      mechanism(s) and the respective contributions of the different components as well
      as the possible interactions between them under physiological or pathological
      conditions await clarification. However, a major role played by the hypothalamic
      release of somatostatin is clearly emerging. The awareness of GH autoregulation,
      and that the amounts of GH used for therapy are at or above the total daily GH
      production suggest caution in the institution of treatment with GH in children
      with idiopathic short stature, although resilience of the endogenous GH-secretory
      machinery would be present in these instances. Ideally, a GH replacement therapy
      should mimic the physiological secretory pattern of GH.

PMID- 1978831
TI  - Similar frequencies of renin gene restriction fragment length polymorphisms in
      hypertensive and normotensive subjects.
AB  - A prospective study was conducted to compare the frequency of renin gene
      polymorphisms in normotensive and hypertensive subjects. Hypertensive (n = 102,
      blood pressure 168 +/- 17/103 +/- 9 mm Hg) and normotensive (n = 120, blood
      pressure 122 +/- 10/75 +/- 9 mm Hg) subjects were white, had similar age and sex
      distributions (hypertensive group, 45 +/- 10 years old and 52% female;
      normotensive group, 44 +/- 9 years old and 55% female) and similar body mass
      index (hypertensive group, 23.2 +/- 2.6; normotensive group, 22.5 +/- 2.4 kg/m2,
      p = 0.048). The familial susceptibility to hypertension was defined as at least
      one parent and one sibling who were hypertensive before age 65; subjects in the
      normotensive group had no familial history of hypertension. Renin gene
      polymorphisms located throughout the renin gene were identified by using three
      restriction enzymes (Taq I, HinfI, HindIII). For each polymorphic restriction
      site, allele frequencies were similar in the hypertensive and the normotensive
      groups. In the absence of parental genotypes, the haplotype frequencies combining
      the three restriction fragment length polymorphisms were estimated by using
      maximum likelihood techniques and were similar in both groups (hypertensive
      group, 0.429, 0.277, and 0.177; normotensive group, 0.453, 0.245, and 0.195 for
      the three most common haplotypes). A rare haplotype detected by Taq I/Hind III
      was apparently more frequent in the hypertensive than in the normotensive group
      (hypertensive group, tH 0.086, th 0.022; normotensive group, tH 0.038, th 0.050),
      but the difference was not statistically significant. In conclusion, no
      association between renin gene polymorphisms and essential hypertension was
      demonstrated in the present study.

PMID- 1978832
TI  - Meningioma and Takayasu disease: case report.

PMID- 1978833
TI  - Tissue-specific enhancer of the human multidrug-resistance (MDR1) gene.
AB  - Identification of cis-regulatory sequences is a first step in analyzing the
      regulation of the human multidrug-resistant 1 (MDR1) gene which encodes the 170
      kilodalton membrane P-glycoprotein in normal tissues and tumor cells. We have
      studied several overlapping genomic clones containing the 5'-flanking region of
      the gene. These clones span about 30 kilobases (kb) of contiguous DNA containing
      10 kb of the gene and 20 kb of the 5'-flanking sequence. The nucleotide sequence
      of the first exon and the 2 kb preceding the exon were determined. DNA sequences
      containing the 5'-flanking regions were linked to the chloramphenicol
      acetyltransferase (CAT) gene. For transient CAT assay, we have employed six cell
      lines, including human cancer KB, vincristine-resistant VJ-300 derived from KB,
      mouse adrenal tumor Y-1, African green monkey kidney CV-1, mouse fibroblast
      NIH3T3, and human adrenal carcinoma SW-13 cells. Promoter activity was very weak
      regardless of the length of the promoter region in mouse adrenal tumor Y-1 and
      monkey kidney CV-1 cells, in which endogenous P-glycoprotein was expressed.
      Introduction of a 700-base genomic DNA fragment from a site located at 10 kb far
      upstream of the initiation site increased the transcription of the CAT gene in Y
      1, CV-1, and SW-13 cells. However, no significant increase in the CAT activity
      could be observed in NIH3T3, KB, and VJ-300 cells. This fragment markedly
      augmented the expression of the CAT gene regardless of orientation or position,
      and it acted in a cell type-specific manner even with heterogenous promoters. Our
      present study suggests that the 700-base pair fragment may carry a tissue
      specific transcriptional enhancer that is active in at least some adrenal and
      kidney-derived cell lines.

PMID- 1978834
TI  - Cloning of the H,K-ATPase beta subunit. Tissue-specific expression, chromosomal
      assignment, and relationship to Na,K-ATPase beta subunits.
AB  - We have isolated cDNA clones encoding the bovine and rat gastric H,K-ATPase beta
      subunit. A bovine abomasum lambda gt11 cDNA library was screened with a
      monoclonal antibody raised against the rabbit H,K-ATPase beta subunit. A single
      positive phage clone containing an approximately 900-base pair cDNA insert was
      identified as reactive with the antibody. The identity of the cDNA was
      established by comparing the deduced amino acid sequence with sequences of
      cyanogen bromide fragments of the porcine H,K-ATPase beta subunit. Polymerase
      chain reaction and rapid amplification of cDNA ends were used to generate a cDNA
      fragment encoding the carboxyl-terminal portion of the rat gastric H,K-ATPase
      beta subunit. A rat stomach cDNA library was screened with the polymerase chain
      reaction product, and several full-length beta subunit cDNA clones were
      identified. The open reading frame predicts a protein of 294 amino acids with a
      molecular weight of 33,689. The rat H,K-ATPase beta subunit shows 41% amino acid
      sequence identity to the rat Na,K-ATPase beta 2 subunit and shares a number of
      structural similarities with Na,K-ATPase beta subunit isoforms. By analyzing the
      segregation of restriction fragment length polymorphisms among recombinant inbred
      strains of mice, we localized the H,K-ATPase beta subunit gene to murine
      chromosome 8. Northern and Western blot analysis reveals that this gene is
      expressed exclusively in stomach. Our results suggest that the H,K-ATPase and
      Na,K-ATPase beta subunits evolved from a common ancestral gene and may play
      similar functional roles in enzyme activity.

PMID- 1978835
TI  - Decreased L system amino acid transport and decreased gamma-glutamyl
      transpeptidase are independent processes in human chronic lymphocytic leukemia B
      lymphocytes.
AB  - The L system of amino acid transport is markedly diminished in chronic
      lymphocytic leukemia (CLL) B-lymphocytes, with a maximal velocity less than 15%
      that of normal B-lymphocytes. Another membrane-associated function, the activity
      of the ectoenzyme, gamma-glutamyl transpeptidase (GGT), is diminished in CLL B
      cells to 30% that of normal B-cells. In addition to its transpeptidase activity,
      a role for GGT has been postulated in the transport of amino acids. In the
      present report, the possible relationship of these two physiologic functions CLL
      B-cells was studied. The L system transport defect in CLL is restored by phorbol
      ester-induced cell maturation; following incubation with 0.15 microM
      tetradecanoyl phorbol acetate (TPA) for 17 hours, the L system initial velocity
      showed a 20-fold increase. In contrast, there was no significant effect on GGT
      activity with cell maturation. Furthermore, an antibody which diminished GGT
      activity by 50% in lymphoid cells did not inhibit L system transport. Thus, the
      impaired L system amino acid transport and GGT activity appear to be independent
      processes in CLL B-cells.

PMID- 1978837
TI  - Identification and partial characterization of genes that are transactivated by
      different pathways in quiescent mouse cells stimulated with serum.
AB  - We have identified four cDNA clones, cl-1, cl-5, cl-15, and cl-16, that represent
      genes induced by serum in resting mouse 3T3 cells. Partial sequence analysis of
      the four cDNAs indicated that cl-15 corresponds to the mouse beta-actin gene.
      Comparison of the DNA sequences of the other three clones with the sequence data
      bank (Genbank) showed little homology to other known DNA sequences and thus
      represent novel genes. The level of the mRNAs corresponding to the four genes
      began to increase in resting cells following serum stimulation, reached a peak
      between 5 h and 8 h and then started to decline. Inhibitors of transcription
      diminished the induction of the mRNAs corresponding to the four genes.
      Cycloheximide and anisomycin had little effect on the induction of beta actin
      mRNA while the induction of the other three genes was suppressed by the same
      inhibitors. 12-O-Tetradecanoylphorbol-13-acetate and the calcium ionophore A23187
      enhanced the expression of the cl-16 mRNA while epidermal growth factor,
      fibroblast growth factor, or insulin enhanced the expression of cl-1- and cl-5
      specific transcripts. The level of beta-actin mRNA was elevated in resting cells
      by epidermal growth factor and 12-O-tetradecanoylphorbol-13-acetate and to a
      lesser extent by fibroblast growth factor, insulin, and dibutyryl cyclic AMP
      elevating agents. Pertussis toxin, an inhibitor of the action of G proteins, did
      not significantly suppress the activation of the four genes by serum. However, 2
      aminopurine, a protein kinase inhibitor, suppressed the induction of the four
      transcripts in serum-stimulated cells. The possible pathways involved in the
      activation of these genes in resting cells are discussed.

PMID- 1978836
TI  - Polarized membrane expression of brush-border hydrolases in primary cultures of
      kidney proximal tubular cells depends on cell differentiation and is induced by
      dexamethasone.
AB  - To analyze the influence of cell differentiation and the effects of hormones on
      the subcellular distribution of apical antigens in polarized epithelial cells, we
      have compared the localization of three brush border (BB) hydrolases [neutral
      endopeptidase (ENDO), aminopeptidase N (APN), and dipeptidylpeptidase IV (DPPIV)]
      in primary cultures of renal proximal tubule cells grown in various culture
      media. The degree of cell differentiation modulated by medium composition was
      estimated by measuring proximal functions, including glucose transport, specific
      enzymatic activities, and PTH responsiveness. In the dedifferentiated state
      observed in cells grown in 1% fetal calf serum (FCS)-supplemented medium, the
      three hydrolases are abnormally concentrated in a cytoplasmic vesicle compartment
      with weak expression on both membrane domains. By contrast, in serum-free
      hormonally defined medium (DM: insulin, 5 microgram/ml; dexamethasone, 5 x 10(-8)
      M), which markedly enhances morphological and functional cell differentiation,
      the distribution of hydrolases parallels that observed in the normal tubule. When
      added to the DM devoid of hormones, insulin has little polarizing effect, whereas
      dexamethasone dramatically increases the apical expression of the hydrolases,
      which then almost disappear from the basolateral membrane and cytoplasmic
      vesicular compartments. This glucocorticoid hormone augments the amount of
      immunoreactive antigen detectable on the apical domain in paraformaldehyde-fixed
      cells but does not change the total enzymatic activity. This suggests the
      presence in tubular cells of a dexamethasone-dependent polarizing machinery that
      requires de novo RNA and protein synthesis, and probably acts mainly by targeting
      a storage cytoplasmic pool of enzyme to the apical domain.

PMID- 1978838
TI  - Glutamine regulates glutamine synthetase expression in skeletal muscle cells in
      culture.
AB  - Metabolite control of glutamine synthetase expression (by glutamine) was studied
      in L6 skeletal muscle cells. Depletion of glutamine from the culture medium for
      24 hours resulted in a 3-4-fold increase in glutamine synthetase activity. This
      effect was blocked by cycloheximide but not by actinomycin D. Addition of
      glutamine to L6 cells maintained in glutamine-free medium caused a rapid return
      of glutamine synthetase activity to the control level. As reported, dexamethasone
      caused a striking increase in the glutamine synthetase mRNA level. In contrast,
      neither depletion nor addition of glutamine caused a change in the glutamine
      synthetase mRNA level. Therefore, regulation of glutamine synthetase by glutamine
      is exerted at a post-transcriptional level.

PMID- 1978839
TI  - Partial down-regulation of protein kinase C reverses the growth inhibitory effect
      of phorbol esters on HepG2 cells.
AB  - Phorbol ester treatment of HepG2, a human tumorigenic cell line, caused rapid
      morphological changes characterized by a flattening and spreading of the cells
      that coincided with a rapid inhibition of thymidine incorporation. Within 24 h,
      cell division was completely inhibited, suggesting the cells had entered a
      quiescent state. Continued incubation in the presence of phorbol esters resulted
      in the resumption of thymidine incorporation and cell division, but this
      coincided with only a partial down-regulation of PKC activity. Seventy-two hours
      of treatment was required to obtain down-regulation of greater than 80% of the
      PKC activity, but reversal of the inhibitory effects occurred between 24 and 48 h
      after the addition of phorbol esters, when a large proportion of the PKC activity
      was still present. Northern blot analysis of a number of transcripts showed that
      the steady-state levels of c-myc and transforming growth factor beta 1 (TGF-beta
      1) messages increased only after 3 h of phorbol ester treatment and returned to
      normal levels after 24 h. C-fos, albumin, and alphafetoprotein messages were not
      affected, suggesting the differentiation state of the cells was not altered.
      Therefore, phorbol ester activation of PKC causes an inhibition of HepG2 cell
      growth initially, but this is unlike the promotion of differentiation seen in
      other systems. Partial down-regulation of PKC activity causes a reversal of the
      growth inhibition and the cells return to a normal growth rate. This effect is
      also clearly different from systems in which phorbol esters have been shown to
      have a mitogenic effect on cells.

PMID- 1978841
TI  - Upper gastrointestinal disease management: an update on therapeutics. Proceedings
      of a symposium. Scottsdale, Arizona, January 1990.

PMID- 1978842
TI  - NSAID-induced gastrointestinal damage. A critical review of prophylaxis and
      therapy.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) cause acute diffuse injury to the
      gastroduodenal mucosa, and also cause chronic focal ulcers that may bleed or
      perforate without warning symptoms. Acute and chronic lesions are distinct, are
      pathogenetically different, respond differently to drugs, and require different
      management strategies. The principal rationale for antiulcer therapy in NSAID
      users is to prevent or reduce potentially fatal outcomes; to date no evaluated
      drug meets this criterion for efficacy. Antacids and H2-receptor antagonists,
      based on open uncontrolled studies, appear to heal both gastric and duodenal
      ulcers, and maintain them healed during continued NSAID use; larger gastric
      ulcers show delayed healing with conventional doses of H2-receptor antagonists
      during NSAID therapy. No such delay occurs with omeprazole therapy. The suggests
      that if NSAID-associated gastric ulcers are treated with H2-receptor antagonists,
      larger doses should be given for longer periods. In patients with no pre-existing
      ulcer disease, H2-receptor antagonists given prophylactically prevent duodenal
      but not gastric ulcers; sucralfate does the same. In individuals without peptic
      ulcer disease taking NSAIDs, misoprostol, given as prophylaxis, reduces the
      development of gastric ulcers; its beneficial effects on ulcer healing or
      symptoms during continued NSAID therapy, or its ability to prevent duodenal
      ulcers or ulcer complications, are not established. Because of diarrhea, the 400
      micrograms/day dosage is recommended, especially in the elderly.

PMID- 1978843
TI  - Gastroesophageal reflux disease: an update on management.
AB  - Gastroesophageal reflux is commonplace; all humans experience it. For many
      patients, gastroesophageal reflux disease (GERD) is a manageable condition. For
      others, GERD can progress to severe symptoms, inflammation, and disruption of the
      mucosal lining. Effective therapy calls for a clear understanding of the
      pathogenesis of GERD. The final common denominator to GERD is a lower esophageal
      sphincter mechanism that relaxes or is incompetent and allows gastroesophageal
      reflux to occur. Key factors associated with GERD are (a) gastric content, (b)
      potency of refluxate, (c) esophageal clearance, (d) tissue resistance, and (e)
      disruption of the anatomic hiatus. GERD is generally a chronic condition
      characterized by recurrent symptoms. Treatment goals for the GERD patient need to
      be defined: is therapy directed toward eliminating the symptoms or is therapy
      designed to eliminate gastroesophageal reflux? Unfortunately, effective therapy
      for GERD usually does not affect the mechanism(s) underlying the problem. The
      broad goals of therapy in GERD are to decrease gastroesophageal reflux and
      neutralize it, to enhance esophageal clearance, and to protect esophageal mucosa.
      The therapeutic modalities related to each of these situations are numerous and
      overlap, but treatment strategies for managing the GERD patient can be used in
      clinical "stages" or as the clinical situation dictates. H2-receptor antagonist
      therapy has become the "keystone" in management of GERD. Unfortunately, not all
      GERD patients respond to conventional H2-receptor antagonist dosage treatment;
      high-dose H2-receptor antagonist therapy recently has been demonstrated to be
      more effective in a greater number of GERD patients with severe
      esophagitis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1978840
TI  - Pathogenesis and therapy of peptic ulcer disease.
AB  - The epithelial cells of the stomach and duodenum are normally protected from the
      damaging effects of acid and pepsin by a balancing mechanism of mucosal
      resistance. If an imbalance occurs, peptic ulcer may result. Traditional teaching
      has emphasized the importance of acid (and pepsin) as the cause of this
      imbalance; however, it is clear that acid and pepsin are not the only important
      factors in the pathogenesis of peptic ulcer. More recent investigative efforts
      have been directed at what constitutes mucosal resistance and how it can be
      disrupted to produce, in the presence of gastric acid, a peptic ulcer. Depletion
      of endogenous prostaglandins and Helicobacter pylori gastritis have emerged as
      prominent theories. As evidence exists both to support and refute these theories
      in humans, any definitive conclusions cannot be made at this time. The acute
      management of peptic ulcer disease is directed at relieving pain, accelerating
      ulcer healing, and preventing complications. Peptic ulcers can be healed with
      antisecretory agents (i.e., H2-receptor antagonists, omeprazole), antacids,
      prostaglandins, and sucralfate. Because they are effective, safe, and convenient,
      the H2-receptor antagonists are the most widely used agents for the management of
      peptic ulcer disease. Because the H2-receptor antagonist agents are equally
      effective in their indicated uses and are equally safe based on scientifically
      valid data, selection should be based primarily on cost. Omeprazole is the newest
      antisecretory agent: a single morning dose of 20 mg suppresses acid secretion for
      24 h. The agent offers little advantage over H2-receptor antagonists for the
      majority of patients with peptic ulcer.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1978844
TI  - Stress-related mucosal damage: review of drug therapy.
AB  - The increased awareness of stress-related mucosal damage (SRMD) that accompanied
      the widespread use of fiberoptic endoscopy and the increased incidence of SRMD
      that accompanied the advances in caring for critically ill patients resulted in
      the recognition that the majority of patients in the intensive care unit (ICU)
      setting wil develop mucosal damage. Complications of gastrointestinal hemorrhage
      in these patients may contribute significantly to their morbidity and mortality,
      and the consequences of this bleeding may be more severe than the underlying
      predisposing conditions. Because of the importance of gastric acid in the
      pathogenesis of SRMD, therapy has focused on reduction of the intraluminal acid
      concentration. Acid neutralization, while effective, is laborious and associated
      with side effects. H2-receptor antagonists have been used successfully in the
      prophylaxis and treatment of SRMD and offer the potential for an effective
      parenteral as well as oral agent. They obviate the need for frequent antacid
      administration and eliminate some of the troubles and side effects that accompany
      an intensive antacid regimen. Of the available H2-receptor antagonists,
      cimetidine has been the most thoroughly evaluated. It is equivalent to antacids
      in the prevention of overt bleeding and offers the advantage of dosing
      flexibility, ease of administration, and a remarkable safety profile. Cimetidine
      has also been shown to be effective when administered by intermittent bolus
      infusions given every 8, 6, or 4 h or by primed continuous infusion, which has
      proven to be the most successful method of controlling intragastric pH.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1978845
TI  - Should safety concerns with available ulcer treatment influence drug selection?
AB  - With the identification of the parietal cell receptors for gastric acid secretion
      coupled with the introduction of cimetidine in 1977, treatment of acid-peptic
      diseases was transformed from empiric therapy to an approach based on a clearer
      understanding of human physiology. Today, physicians are confronted with an array
      of antiulcer agents that differ within their drug class (e.g., the H2-receptor
      antagonists) as well as in their mechanisms of action (e.g., neutralize acid,
      alter mucosal defensive factors, or suppress acid secretion). With minor
      exceptions, the clinical efficacy of the available antiulcer drugs can be
      regarded as comparable. Thus, the safety profile becomes the next consideration
      when choosing among similarly effective drug products. Of the available antiulcer
      agents, the H2-receptor antagonists as a class have an excellent safety profile,
      as indicated by more than 25 years of cumulative clinical experience and
      postmarketing surveillance. Important safety issues with currently available
      antiulcer drugs, i.e., H2-receptor antagonists, sucralfate, prostaglandin E
      analogues, and the newest antiulcer agent, omeprazole, are reviewed to place them
      into perspective for the clinician.

PMID- 1978846
TI  - Antiulcer therapy: an exercise in formulary management.
AB  - The purpose of formulary management is to contain costs while preserving quality
      care. A pharmacy cost review can identify key areas where limiting the agents
      used could lower costs. H2-receptor antagonists represent such agents. At UC
      Davis Medical Center, H2-receptor antagonists were found to be one of the highest
      cost drug groups in the hospital. Seventy percent of H2-receptor antagonist use
      was for intravenous prophylaxis of stress ulcer. After a committee review of
      available data, H2-receptor antagonists were considered therapeutically
      equivalent. Cimetidine was chosen as the primary H2-receptor antagonist because
      of an estimated 36% cost savings. Inpatient H2-receptor antagonist use changed
      from 90% ranitidine prior to the decision to 90% cimetidine after the decision. A
      monitoring program revealed that there were similar numbers of elevated drug
      levels for theophylline, phenytoin, and lidocaine before and after the
      programmatic change. There was no difference in numbers of patients with
      theophylline toxicity on cimetidine or ranitidine. The incidence of bleeding from
      stress ulcer was 1.4% in the year following the change to cimetidine use. With
      aggressive review and utilization of scientific data, cost-saving H2-receptor
      antagonist restriction decisions can be made that do not compromise quality care.

PMID- 1978847
TI  - Inhibition by anti-HLA class II monoclonal antibodies of monoclonal antibody OKT3
      induced T cell proliferation. Studies at the mRNA level.
AB  - mAb to monomorphic determinants of HLA class II Ag have been shown to inhibit
      monocyte-dependent OKT3-induced T cell proliferation, indicating that MHC class
      II molecules play a regulatory role also in Ag nonrestricted, CD3-induced T cell
      proliferation. This effect involves several steps in the process of T cell
      activation and proliferation, including IL-1 beta, IL-6, and IL-2 secretion and
      IL-2R alpha expression. In the present study, we analyzed the effect of an anti
      HLA class II mAb (Q5/6) on the mRNA expression of genes related to monocyte and T
      cell activation. mRNA levels for early (early c-myc, c-fos) and late (late c-myc,
      N-ras, c-myb) genes involved in T cell activation were determined as well as mRNA
      levels for IL-1 beta, IL-6, IFN-gamma, IL-2, and IL-2R alpha. The kinetics of
      mRNA induction for ICAM-1 was also investigated. The results show that in T
      lymphocytes the expression of c-fos and early c-myc mRNA was unaffected by mAb
      Q5/6, whereas the c-myb and N-ras mRNA levels were strongly diminished as well as
      those of IL-2, IL-2R alpha, and IFN-gamma mRNA. An early increase of ICAM-1 mRNA
      was partially inhibited. In monocytes, a marked reduction of IL-1 beta and IL-6
      mRNA was found. It is concluded that the HLA class II determinant involved in the
      inhibition mechanism can be engaged in the control of IL-1 beta and IL-6 mRNA
      levels and constitute an accessory signal up-regulating IL-2 and IL-2R alpha gene
      activation, through a pathway not affecting c-myc and c-fos expression.

PMID- 1978848
TI  - HIV inhibits the early steps of lymphocyte activation, including initiation of
      inositol phospholipid metabolism.
AB  - Mechanisms accounting for HIV-associated suppression of lymphocyte proliferation
      were investigated. In previous work we demonstrated that purified and inactivated
      HIV-suppressed lymphoid cell proliferation. In this report we used an inactivated
      preparation of HIV obtained from infected CEM cells grown in serum free media and
      demonstrated that this HIV-associated suppression acted in the early steps of
      activation to inhibit the incorporation of radiolabeled phosphorus into
      phosphatidylinositol 4,5-bisphosphate and phosphatidic acid. Initially we showed
      that both purified CD4 and CD8 T lymphocyte subsets were affected and HIV
      associated inhibition did not require the CD4 molecule. Impaired lymphocyte
      blastogenesis (decreased size and granularity and decreased expression of
      receptors to IL-2 and transferrin) in response to PHA indicated an effect of
      inactivated HIV on the early steps of activation. This was confirmed by time
      studies where 1) a 2 min HIV-pretreatment followed by washing before stimulation
      was sufficient to inhibit PHA induced proliferation of normal lymphocytes, and 2)
      addition of HIV to PHA prestimulated lymphocytes failed to inhibit proliferation,
      e.g., there was no effect on preactivated lymphocytes. HIV was mainly inhibitory
      of lymphocyte proliferation induced by PHA or mAb to the CD3 receptor. In
      contrast to the effect on the CD3/TiR, responses via the CD2 receptor were not
      suppressed, e.g., stimulation with the monoclonal antibodies T11(2) + T11(3).
      Inasmuch as responses by direct A23187 + PMA stimulation of intracellular
      pathways were also inhibited, it appears that the HIV-induced defect was not (or
      not only) membrane receptor mediated. The earliest (min) measurable event after
      stimulation was the initial increase in intracellular Ca2+ which was unaffected
      by HIV pretreatment. The next measurable event (min to h) of stimulation is a
      sustained increase in inositol phospholipid turnover. Pretreatment of mononuclear
      cells with inactivated HIV resulted in a decreased inositol phospholipid turnover
      as judged from decreased 32P incorporation into phosphatidylinositol 4-phosphate
      and phosphatidylinositol 4,5-bisphosphate. This led to decreased generation of
      DAG as reflected in the reduced radiolabeling of its metabolite PA. Reduced
      availability of DAG presumably interferes with pkC activation and leads to
      decreased expression of receptors for IL-2 and transferrin and impaired
      proliferation.

PMID- 1978849
TI  - Glutathione S-transferase. Novel vaccine against Fasciola hepatica infection in
      sheep.
AB  - The potential of GST as a vaccine candidate against liver fluke infection in
      ruminants was studied by vaccinating sheep (n = 9) with GST purified from adult
      worms of Fasciola hepatica and challenging with 500 F. hepatica metacercariae.
      The immunization induced a high antibody response to GST in contrast to the poor
      or undetectable response to this Ag observed in naturally infected sheep.
      Throughout the trial, the progress of the fluke infection was monitored by
      measuring RBC hemoglobin levels, the extent of liver damage and the fecal egg
      output in the sheep. This analysis indicated that a subpopulation (n = 4) of the
      GST vaccinated animals exhibited no anemia, reduced liver damage and a lower mean
      fecal egg count relative to the infected control group suggesting a lower fluke
      burden in these animals. Worm burdens in the livers of the GST vaccine group (107
      +/- 22) were 57% lower than in the infected control group (250 +/- 25). The
      subpopulation of the GST vaccine group demonstrated a 78% reduction in mean worm
      burdens relative to the control group. These results show that GST of adult F.
      hepatica is a novel Ag that can significantly protect sheep against liver fluke
      infection. The results suggest that the immune response to GST is directed to the
      juvenile worm reducing the number of worms that can establish in the liver of the
      vaccinated animals.

PMID- 1978850
TI  - Kinetics of chromosome lesion repair in synchronized quiescent and proliferating
      CHO cells.
AB  - The induction of chromosome aberrations by X-rays was investigated in
      synchronized quiescent and proliferating CHO-K1 cells. Kinetics of chromosome
      lesion repair was studied using the method of fractionated irradiation. In both
      cell types the time-course of repair during fractionation intervals followed
      first-order kinetics. Comparison with kinetic data reported on DNA double-strand
      break repair supports the hypothesis that DNA double-strand breaks are the
      lesions underlying chromosome aberration formation. Quiescent CHO cells showed
      higher aberration yields than proliferating cells, and chromosome lesion repair
      was faster in quiescent cells. This correlation can be interpreted in terms of a
      higher degree of repair synchronism during pairwise lesion interaction. The
      effect of delayed plating on aberration induction was studied in quiescent cells.
      The time-course of repair active during the delayed plating interval followed
      first-order kinetics. The kinetics observed in delayed plating experiments is
      slower than the repair kinetics observed in fractionation experiments, suggesting
      the involvement of two different processes.

PMID- 1978851
TI  - Dynamic measurements of hexafluoromisonidazole (CCI-103F) retention in mouse
      tumours by 1H/19F magnetic resonance spectroscopy.
AB  - Selective retention of hexafluoromisonidazole, CCI-103F, in RIF-1 and SCCVII
      tumours of C3H/Km mice has been measured by 1H/19F magnetic resonance
      spectroscopy (MRS) on a Bruker AM-400 multinuclear spectrometer. CCI-103F
      concentrations in tumours and in normal tissues were measured using an MRS
      technique in which the water component in the tissues serves as an internal
      concentration reference. The biodistribution and elimination half-life of the
      drug in the tissues after i.p. injections were determined. The plasma half-life
      of the drug (41 min) was measured by high-pressure liquid chromatography. The two
      tumour lines and liver have longer retention times with half-lives of 47, 129 and
      81 min, respectively, while normal tissues, muscle and brain have little
      retention of CCI-103F and clear the drug very quickly. Dynamic measurements of
      CCI-103F retention in tumours by MRS may provide a non-invasive probe for
      assessing tumour hypoxia.

PMID- 1978852
TI  - Apparently beneficial effect of low to intermediate doses of A-bomb radiation on
      human lifespan.
AB  - Among about 100,000 A-bomb survivors registered at Nagasaki University School of
      Medicine, 290 male subjects exposed to 50-149 cGy showed significantly lower
      mortality from non-cancerous diseases than age-matched unexposed males. This was
      deduced from the fitting of a U-shaped dose-response relationship. Reasons for
      this effect in males, but not in females, are discussed with reference to
      selection of individuals and to hormesis.

PMID- 1978853
TI  - A comprehensive study of the radiobiological response of the murine (BDF1) small
      intestine.

PMID- 1978854
TI  - Mutation induction in V79 Chinese hamster cells by very heavy ions.
AB  - Mutation induction (resistance to 6-thioguanine) in Chinese hamster fibroblasts
      (V79) by exposure to accelerated heavy ions (O, Ne, Ca, Ti, Ni, Xe, Pb and U with
      energies between 5 and 14.8 MeV/u) was investigated, covering a range of LET from
      300 to about 15,700 KeV/micron. The LET-dependence of the mutation induction
      cross-section (sigma m) has, in a similar way to inactivation (sigma i), to be
      described by separate curves for each ion. Both sigma m and mutagenicity (sigma
      m/sigma i) decrease with increasing specific energy for any given ion. Relative
      biological effectiveness for mutation induction was found to be significantly
      smaller than unity for the ions and energies investigated.

PMID- 1978855
TI  - Establishment of a novel immortalized cell line from ataxia telangiectasia
      fibroblasts and its use for the chromosomal assignment of radiosensitivity gene.
AB  - An immortalized cell line was established from a female ataxia telangiectasia
      (AT) patient by the transfection of primary skin fibroblasts with origin
      defective SV40 DNA. The cell line was characterized by a hypodiploid chromosome
      constitution and radiation hypersensitivity. The established cell line was used
      as a recipient for microcell-mediated chromosome transfer. Among seven G418
      resistant clones obtained by the fusion with microcells from mouse A9 cells
      carrying a pSV2neo-tagged normal human chromosome 11, three clones showed
      restoration of radiation resistance with concomitant gain of an extra intact
      chromosome 11, while the others contained no recognizable or deleted chromosome
      11. The association of the presence of 11q14----qter region with the
      radioresistance suggests the presence of AT gene in this chromosomal region.

PMID- 1978856
TI  - Chromosome aberrations induced in human lymphocytes by 16.5 MeV protons.
AB  - In a track segment irradiation experiment with 16.5 MeV protons the induction of
      dicentrics was studied in human T-lymphocytes. The dose-response relationship was
      linear quadratic with estimated parameters alpha = (0.44 +/- 0.07) x 10(-1) Gy-1
      and beta = (1.95 +/- 0.30) x 10(-2) Gy-2. With respect to X-rays a limiting RBE
      of 1.1-1.2 exists. The present findings are compared with data from other
      laboratories obtained with 4.9 and 8.7 MeV protons. It was found that the data do
      not fit theoretical predictions on a proportional relationship between alpha
      values and LET. Using the microdosimetric quantity yD (25 nm), the dose average
      of the lineal energy, for characterization of these proton radiations, at a
      relevant site diameter of 25 nm the ratio of yD = 1.15 is in accordance only with
      the observed alpha ratio of 1.0 +/- 0.23 for 8.7 and 16.5 MeV protons. In
      contrast to the prediction of a constant beta at low LET values, the quadratic
      coefficients increase with increasing LET between 3 and 8 keV/microns.

PMID- 1978857
TI  - Human immunodeficiency virus and the primary care physician.
AB  - As the scope and size of the human immunodeficiency virus (HIV) epidemic grows,
      the primary care physician will need to assume a greater role. A knowledge of HIV
      risk factors and the ability to perform pretest and posttest counseling for HIV
      testing is essential. Counseling patients on HIV risk reduction should be part of
      the HIV risk interview. An understanding of the benefits and contraindications of
      testing, as well as a respect for the impact of testing, is important. All HIV
      seropositive individuals should undergo a complete history and review of symptoms
      as soon as test results are known. Judicious use of laboratory testing, including
      monitoring of CD4 cell counts, is recommended. Pneumocystis carinii prophylaxis
      and zidovudine therapy should be offered to patients with appropriately low CD4
      counts.

PMID- 1978858
TI  - Sulpiride in tardive dyskinesia.
AB  - The abnormal involuntary movements in tardive dyskinesia can be reduced by the
      dopamine antagonist drugs, phenothiazines and butyrophenones, but most cause an
      increase in Parkinsonian signs. Sulpiride, a benzamide derivative, and selective
      antagonist of D2 receptors had a significantly beneficial effect on most of 15
      patients (p less than 0.01). In 12 patients the improvement was marked. The
      reduction of abnormal movements was observed even with low doses, and it was not
      necessary to increase the dose of sulpiride above 600 mg daily. There were no
      significant side effects during the trial nor during an additional three months
      of treatment.

PMID- 1978859
TI  - Are omega-3 fatty acids required for normal eye and brain development in the
      human?

PMID- 1978861
TI  - Two step procedure for early diagnosis of polycystic kidney disease with
      polymorphic DNA markers on both sides of the gene.
AB  - Polymorphic DNA markers can now be used for presymptomatic and prenatal diagnosis
      of the autosomal dominant form of polycystic kidney disease (PKD). A detailed map
      is known for the chromosomal region around the PKD1 gene on the short arm of
      chromosome 16. We present here a simple, two step procedure for diagnosis of PKD1
      by family studies. Using this approach, at least 92% of random subjects are
      informative for polymorphic DNA markers bracketing the PKD1 gene. The
      recombination rate between these flanking markers is on average 10%. In non
      recombinants (90% of family members), the accuracy of diagnosis using DNA markers
      is greater than 99%. We conclude that sufficient well defined DNA markers are now
      available for routine diagnosis of PKD1. We recommend, however, that prenatal
      diagnosis of PKD by chorionic villi sampling should be attempted only after the
      linkage phase of the DNA markers has been established by haplotyping the index
      family. Since autosomal dominant PKD has been found to be genetically
      heterogeneous, families should be of sufficient size to rule out the rare form of
      PKD not caused by a mutation on the short arm of chromosome 16.

PMID- 1978860
TI  - Map of 16 polymorphic loci on the short arm of chromosome 16 close to the
      polycystic kidney disease gene (PKD1).
AB  - To define the PKD1 locus further, the gene involved in the most frequent form of
      adult polycystic kidney disease, probes from 16 polymorphic loci were mapped on
      16p13.1-pter with the combined use of cell lines containing rearranged
      chromosomes and family studies. Five breakpoints in the distal part of 16p
      arbitrarily subdivided the loci into five groups. By analysing 58 recombination
      events among 259 informative meioses in 12 large families with PKD, we were able
      to construct a linkage map for the distal part of 16p. The order of the markers
      obtained with chromosomal rearrangements was confirmed by the family studies. The
      D16S85 locus near alpha globin, D16S21, and D16S83 map distal, or telomeric, to
      PKD1. The polymorphic red cell enzyme phosphoglycolate phosphatase (PGP), D16S84,
      D16S259, and D16S246 showed no recombination with PKD1. The remaining nine RFLPs
      all map proximal to the PKD1 gene. By cosmid walking, additional RFLPs were
      detected at the D16S21 locus. A single intrahaplotype recombination observed
      defines the orientation of D16S21 relative to PKD1. The new polymorphisms are
      valuable for presymptomatic and prenatal diagnosis of PKD1. Furthermore, our map
      is both a good starting point for the physical map of 16p and a useful tool for
      the isolation of the PKD1 gene.

PMID- 1978863
TI  - [A study on the utility of flumazenil for patients in the ICU].
AB  - Flumazenil, a specific antagonist of benzodiazepines, was administered to adult
      patients receiving treatment at ICU, and its utility to hasten recovery from
      sedation was evaluated in 40 patients and its usefulness for differential
      diagnosis of sedated conditions was also evaluated in 5 patients. The efficacy
      rate for recovery from sedation induced by benzodiazepines was 85.0%. Moreover,
      flumazenil was considered to be useful for differentiation of sedated conditions
      when causes were unknown. Depression of respiration improved in association with
      improvement of consciousness level. In some patients an elevation in blood
      pressure was also observed with improved consciousness.

PMID- 1978862
TI  - A study of H2 receptor antagonists in the treatment of chronic intractable
      pharyngitis.
AB  - In a controlled study of 75 patients suffering from chronic pharyngitis: 30 were
      treated with H2-receptor antagonist, 30 with H1-receptor antagonist, local
      decongestants and antiseptic gargles: and 15 treated with alum, salt or Dispirin
      gargles acted as controls. Best response was obtained with the first mode of
      treatment, raising the possibility of role of the H2-receptors in causing chronic
      pharyngitis. The difference was highly significant (P less than 0.001).

PMID- 1978864
TI  - [Hemodynamic changes with sufentanil-oxygen anesthesia for open heart surgery--a
      comparison of patients with beta-blocking medication or without it].
AB  - We investigated hemodynamic changes in patients undergoing coronary artery bypass
      grafting (CABG) and valve replacement. The former had been medicated with beta
      blocking agent until the morning of operative day. On the other hand, the latter
      received no medication. We measured systolic arterial pressure (SAP), diastolic
      arterial pressure (DAP), mean arterial pressure (MAP), heart rate, and rate
      pressure product (RPP) at the following five points; before induction of
      anesthesia, immediately before intubation, immediately after intubation, one
      minute after skin incision and one minute after sternotomy. In both groups, SAP
      and DAP decreased significantly after induction; heart rate did not change during
      our study; and RPP decreased significantly after skin incision. There were no
      significant differences between the group with beta-blocking agent and the group
      without it. These results suggest that beta-blocking agents exert no influence in
      our study, and sufentanil-oxygen anesthesia produce hemodynamic stability for
      open heart surgery.

PMID- 1978865
TI  - [Study of neuromuscular transmission with evoked electromyography--10. Comparison
      of the responses during partial blockade by bungarotoxin and non-depolarizing
      relaxants].
AB  - Effects of alpha-bungarotoxin (alpha BuTX) on muscle compound action potentials
      (CAPs) which were elicited from gastrocnemius muscle by sciatic nerve stimulation
      in cats were studied, and the results were compared with those of non
      depolarizing relaxants including d-tubocurarine, pancuronium and vecuronium. The
      amplitude of CAP by the second member of the paired stimuli (test response) was
      compared with that evoked by the first component (conditioning response). The
      interval between the two components of the paired stimuli (the pair interval) was
      increased stepwise from 7 to 1,000 msec and a curve (recovery curve, RC) was
      obtained by relating the changes in pair interval to the difference in amplitude
      of the test and conditioning responses. The following results were obtained. (1)
      A progressive and irreversible neuromuscular block was observed after intravenous
      administration of alpha BuTX. During the progress of the blockade, RC of CAPs
      showed a pattern which was characterized by profound potentiations of test
      responses at shorter intervals of paired stimuli, followed by gradual recovery to
      similar amplitude with conditioning responses at 500 msec or over of pair
      interval. (2) With non-depolarizing relaxants, RC changed to the pattern of
      slight potentiation at a very short interval of stimuli, followed by a notable
      depression at longer intervals. (3) The mechanism of the development of these
      difference of RCs between alpha BuTX and the relaxants was discussed, and it is
      concluded that the notable depression of RCs derived from muscle relaxants may be
      caused by inhibitory effect on nerve terminals of these relaxants, and the
      inhibition was more prominent with d-tubocurarine than with other two relaxants.

PMID- 1978866
TI  - [Influence of small doses of vecuronium and pancuronium on succinylcholine
      induced neuromuscular blockade].
AB  - The effects of pretreatments with vecuronium (VB) and pancuronium (PB) on
      succinylcholine (SCC)-induced neuromuscular blockade were evaluated in 266
      patients using electromyographic responses to train-of-four (TOF) ulnar nerve
      stimulation repeated every 20 seconds. Seventy-five patients served as the
      control group and received 1 mg.kg-1 SCC without pretreatment with VB or PB.
      Other 191 patients were divided into three groups according to the type and
      dosage of pretreatment as follows: VB 20 micrograms.kg-1, VB 14 micrograms.kg-1
      and PB 20 micrograms.kg-1. Five minutes after each pretreatment. SCC 1 mg.kg-1
      was administered intravenously. All patients were intubated after SCC injection
      and then anesthesia was maintained with nitrous oxide and enflurane. Among
      pretreatment groups, the maximal amplitude response to TOF stimuli and TOF ratio
      were depressed most by 20 micrograms.kg-1 VB and least by 20 micrograms.kg-1 PB
      at the time of SCC administration. All pretreatments delayed the onset time from
      SCC injection to maximal blockade compared with that of control group. Maximal
      blockade induced by SCC was significantly less in VB 20 micrograms.kg-1 group
      than that in other pretreatment and control groups. The duration of action of SCC
      was shortened by pretreatments with two dosages of VB but prolonged by PB
      pretreatment. TOF ratio during the recovery phase was depressed in all
      pretreatment groups than that in control group. It is demonstrated that a non
      depolarizing muscle relaxant, VB has relatively potent antagonistic action on SCC
      induced effects, although another potent agent, PB exerts antagonistic action
      only slightly.

PMID- 1978867
TI  - [A case report of coronary artery bypass grafting with the left internal mammary,
      the right gastroepiploic, and the inferior epigastric arteries].
AB  - We performed coronary artery bypass grafting with the left internal mammary
      artery, right gastroepiploic artery, and inferior epigastric artery on a 60-year
      old male. The inferior epigastric artery used as a free graft was placed between
      the in situ left internal mammary graft proximally and the obtuse marginal branch
      distally. Both the left internal mammary graft to the left anterior descending
      artery and the right gastroepiploic artery to the right coronary artery were used
      as an in situ graft. All grafts were patent two weeks after the operation and the
      patient was free from angina at three months follow-up period.

PMID- 1978868
TI  - [Coronary artery bypass grafting with combined arterial grafts].
AB  - Coronary artery bypass grafting with combined arterial graft using the left
      internal mammary artery (IMA), right IMA, and the right gastroepiploic artery
      (GEA) was performed in 45 patients with saphenous vein graft (SVG) (29 patients)
      or without SVG (16 patients) from February 1989 to October 1989. The left IMA was
      used in all patients, the right IMA was used in 9 patients, and the GEA was used
      in 43 patients. Perioperative myocardial infarction was noted in two patients who
      had hospital deaths. Reopening the chest for postoperative bleeding was performed
      in two patients, and the cerebral accident was noted in one patient. Fourteen
      patients were operated on without the requirement for blood transfusion. Studied
      within 3 postoperative months, all arterial grafts were patent though the patency
      was 97.7% (43/44) in SVG. It is concluded that the combined arterial graft
      utilizing the IMAs and GEA can be used safely and effectively.

PMID- 1978869
TI  - Molecular cloning of cDNA for human mitochondrial acetoacetyl-CoA thiolase and
      molecular analysis of 3-ketothiolase deficiency.

PMID- 1978870
TI  - The human prolidase gene: structure and restriction fragment length
      polymorphisms.

PMID- 1978871
TI  - Regular inhaled beta-agonist treatment in bronchial asthma.
AB  - 89 subjects with stable asthma took part in a double-blind, placebo-controlled,
      randomized, crossover study of the effects of regular versus on-demand inhaled
      bronchodilator therapy. The subjects inhaled fenoterol or placebo by a dry powder
      delivery system for 24 weeks. Control of asthma was judged by daily morning and
      evening peak expiratory flow rates, symptom diaries, use of additional inhaled
      bronchodilator, and requirement for short courses of prednisone. Of 64 subjects
      who completed the trial, 57 showed a clear difference in degree of control of
      asthma between the fenoterol and placebo periods: in 17 (30% [95% confidence
      interval 18.4-43.4%]) asthma was better controlled during regular inhaled
      bronchodilator treatment, whereas in 40 (70% [56.6-81.6%]) control was better
      during placebo treatment with bronchodilator for symptom relief only. Mean airway
      responsiveness to methacholine increased slightly during the fenoterol period.
      The adverse effect of regular bronchodilator inhalation occurred not only among
      subjects who used a bronchodilator as sole treatment (2 were better and 10 were
      worse during regular bronchodilator treatment) but also among those who took
      inhaled corticosteroids (14 were better and 29 were worse). Thus, regular
      inhalation of a beta-sympathomimetic agent was associated with deterioration of
      asthma control in the majority of subjects. The trends to use of regular, higher
      doses or longer-acting inhaled beta-sympathomimetic treatment may be an important
      causal factor in the worldwide increase in morbidity from asthma.

PMID- 1978872
TI  - Bronchodilator, cardiovascular, and hypokalaemic effects of fenoterol,
      salbutamol, and terbutaline in asthma.
AB  - The airway response and cardiovascular and hypokalaemic effects of fenoterol,
      salbutamol, and terbutaline given in multiples of standard doses from metered
      dose inhalers were studied in ten patients with mild asthma. In a double-blind,
      crossover, placebo-controlled study the subjects received 2, 6, and 18 puffs of
      each drug with intervals of 90 min, and forced expiratory volume in 1 s, heart
      rate, QTc interval, plasma potassium concentration, tremor, and bronchial
      reactivity to histamine were measured. All three drugs produced similar
      bronchodilatation. However, the rises in heart rate, QTc interval, and tremor and
      the fall in plasma potassium were greater after fenoterol than after salbutamol
      or terbutaline. The maximum mean (SD) increases in heart rate for fenoterol,
      salbutamol, and terbutaline were 29 (24) bpm, 8 (9) bpm, and 8 (14) bpm,
      respectively; falls in plasma potassium were 0.76 (0.62) mmol/l, 0.46 (0.32)
      mmol/l, and 0.52 (0.39) mmol/l, respectively. Fenoterol afforded no additional
      protection against histamine compared with salbutamol. These findings suggest
      that at doses based on those used in clinical practice fenoterol causes more
      adverse effects than salbutamol or terbutaline. The most likely explanation for
      these effects is that fenoterol has been marketed at a higher dose than the other
      beta 2-agonists; fenoterol may in addition be less selective for beta 2
      receptors.

PMID- 1978873
TI  - Amoxycillin plus probenecid versus doxycycline for treatment of erythema migrans
      borreliosis.
AB  - 72 adults with erythema migrans (early Lyme borreliosis) were enrolled in a
      randomised prospective trial comparing amoxycillin 500 mg plus probenecid 500 mg
      three times a day with doxycycline 100 mg twice a day for 21 days. These
      antibiotic regimens were chosen because of the known in-vitro sensitivity of
      Borrelia burgdorferi, the antibiotic tissue penetration, the pharmacokinetics of
      the drugs, and because the organism can disseminate early in the course of
      infection. 72 patients were evaluable (35 in the doxycycline group and 37 in the
      amoxycillin/probenecid group). The two regimens were equally effective for
      treatment of erythema migrans. Mild fatigue or arthralgia were the only post
      treatment complaints, which resolved within 6 months. None of the patients needed
      further antibiotic treatment for Lyme borreliosis.

PMID- 1978874
TI  - High antigen reactivity in mononuclear cells from sites of chronic inflammation.
AB  - Antigen-specific in-vitro responses of mononuclear cells from synovial fluid and
      peripheral blood of patients with rheumatoid arthritis were compared with those
      of mononuclear cells from pleural exudate and peripheral blood of non-rheumatoid
      arthritis patients with chronic pleuritis not caused by tuberculosis. The
      antigens tested were an acetone-precipitable fraction of Mycobacterium
      tuberculosis (AP-Mt), an Escherichia coli lysate containing the 65 kD heat-shock
      protein of M bovis BCG (65 kD/E coli), the M bovis heat-shock protein alone (65
      kD), and E coli alone. The mean proliferative responses to AP-Mt were higher in
      synovial-fluid than in peripheral-blood mononuclear cells in rheumatoid arthritis
      patients (mean [SEM] stimulation index 10.5 [3.1] vs 2.6 [0.9]) and in pleural
      exudate than in peripheral-blood mononuclear cells in the pleuritic patients (7.5
      [1.7] vs 3.5 [2.0]). The same pattern was seen for the other three antigens. Only
      1 of 26 synovial-fluid mononuclear cell samples from rheumatoid arthritis
      patients showed a positive response (stimulation index 3 or more) to 65 kD
      compared with 5 of 22 pleural-exudate mononuclear cell samples, so 65 kD seems
      not to be the major antigen recognised by synovial-fluid T cells in rheumatoid
      arthritis. Enhanced reactivity against mycobacterial and other bacterial antigens
      is not restricted to mononuclear cells from chronically inflamed joints but seems
      to be a common feature of chronic inflammation.

PMID- 1978875
TI  - Beta 2 agonists in asthma: relief, prevention, morbidity.

PMID- 1978876
TI  - G proteins and heart failure.

PMID- 1978877
TI  - HCV and autoimmune liver disease.

PMID- 1978878
TI  - Promoting health research for development.

PMID- 1978879
TI  - CRH test in the 1990s.

PMID- 1978880
TI  - Human recombinant GM-CSF in allogeneic bone-marrow transplantation for leukaemia:
      double-blind, placebo-controlled trial.
AB  - In a randomised, double-blind trial 20 patients with leukaemia received human
      recombinant granulocyte macrophage colony-stimulating factor (GM-CSF) and 20
      received placebo, for 14 days after allogeneic, matched sibling, bone-marrow
      transplantation. The neutrophil count recovered to 0.5 x 10(9)/l 3 days earlier
      in the GM-CSF group than in the placebo group (not significant), and the median
      neutrophil count at 14 days was significantly higher in the GM-CSF group (1.90 vs
      0.46 x 10(9)/l). The lymphocyte count was significantly higher in the GM-CSF than
      in the placebo group between days 10 and 15 after transplantation, but this
      difference was not associated with a higher incidence of graft-versus-host
      disease. There was no evidence that GM-CSF was associated with a greater
      incidence of leukaemic relapse. The GM-CSF group had lower haemoglobin
      concentrations and platelet counts and higher plasma urea, creatinine, and
      bilirubin than the placebo group. The duration of hospital stay was the same for
      both patient groups. Further studies are now indicated to assess the overall
      effect of GM-CSF on outcome after allogeneic bone-marrow transplantation.

PMID- 1978882
TI  - Bird attack on milk bottles: possible mode of transmission of Campylobacter
      jejuni to man.
AB  - A case-control study was carried out to test the hypothesis that the rise in the
      rate of Campylobacter jejuni infection in the Brigend area of South Wales during
      May was due to the consumption or handling of milk from bottles that had been
      attacked by birds. 32 of 36 cases meeting the case definition were interviewed,
      along with 2 controls per case, matched for age, sex, and area of residence.
      There were strong associations between campylobacter infection and doorstep
      delivery of milk bottles, a history of milk bottle attack by birds, milk bottle
      attack by birds during the week before illness, and consumption of milk from
      attacked bottles during the week before illness. There was a very strong dose
      response relation between frequency of bird attack and illness. Controls with a
      history of milk bottle attack by birds were more likely than cases to have taken
      preventive measures against bird attack and consumption of contaminated milk.
      Although few people witnessed the attacks, the likely culprits are magpies (Pica
      pica) and jackdaws (Corvus monedula).

PMID- 1978881
TI  - Echocardiographic evaluation of patients with clinically suspected arterial
      emboli.
AB  - 153 patients (mean age 42 years, range 16-60) who had arterial embolic events
      were examined prospectively by transthoracic and transoesophageal
      echocardiography. Patients older than 60 years and those with evidence of
      extracranial carotid artery occlusive disease were excluded. 84 patients had a
      cerebral ischaemic event, 50 patients had embolic events in an abdominal organ or
      limb, and 19 patients had acute retinal ischaemia. The transthoracic
      echocardiographic examination was normal in 92 patients (60%), whereas only 65
      patients (42%) had normal findings after both transthoracic and transoesophageal
      examination (p less than 0.005). Intracardiac masses, including valvular
      vegetations, were found in 39 patients (25%), including 27% of patients with
      cerebral embolism and 32% of these with peripheral embolism, but in none of the
      patients with retinal ischaemia (p less than 0.001). 47 patients (31%) had
      valvular disease, 10 (7%) had wall motion abnormalities, 23 (15%) had
      abnormalities of the interatrial septum, and 9 patients (6%) had diseases of the
      thoracic aorta. Cardiovascular abnormalities were frequently found by
      echocardiography in patients with arterial emboli. The transesophageal technique
      significantly increased the chance of detecting such abnormalities, especially
      intracardiac masses.

PMID- 1978883
TI  - Foodborne protozoal infection.

PMID- 1978884
TI  - Mianserin side-effects.

PMID- 1978885
TI  - Buruli ulcer in West Africa.

PMID- 1978886
TI  - Lack of diagnostic value of guineapig test for tuberculosis.

PMID- 1978887
TI  - Treatment of first relapse in acute promyelocytic leukaemia with all-trans
      retinoic acid.

PMID- 1978888
TI  - Hantavirus infection presenting as acute renal failure.

PMID- 1978889
TI  - Congenital hydrocephalus due to intrauterine HTLV-I infection.

PMID- 1978890
TI  - Cryptococcus neoformans var gattii.

PMID- 1978891
TI  - Anti-HCV false positivity in malaria.

PMID- 1978892
TI  - Cisapride and brittle asthma.

PMID- 1978893
TI  - Low intraocular pressure in seasonal affective disorder.

PMID- 1978894
TI  - Digital clubbing.

PMID- 1978895
TI  - New drug danger for children.

PMID- 1978896
TI  - Monocyte activation and increased procoagulant activity in unstable angina.

PMID- 1978898
TI  - Sydney classification for gastritis and Helicobacter pylori.

PMID- 1978897
TI  - Helicobacter pylori and metronidazole resistance.

PMID- 1978899
TI  - Risks for physicians handling antineoplastic drugs.

PMID- 1978900
TI  - Taste disturbance with acetazolamide.

PMID- 1978901
TI  - Effect of sodium monofluorophosphate and calcium on bone density and fracture
      rate in osteoporosis.

PMID- 1978902
TI  - Carcinoma and endometrial thickness.

PMID- 1978904
TI  - Medical aspects of torture.

PMID- 1978903
TI  - Malnutrition and falls.

PMID- 1978905
TI  - Prisoners of conscience in Sudan.

PMID- 1978906
TI  - Self-experimentation by doctors.

PMID- 1978907
TI  - Ethics committees.

PMID- 1978908
TI  - Plasma endothelin and renal function during infrarenal aortic crossclamping and
      nifedipine infusion.

PMID- 1978909
TI  - Infant botulism due to Clostridium botulinum type C toxin.

PMID- 1978910
TI  - Eicosapentaenoic acid composition of different fish oil concentrates.

PMID- 1978911
TI  - Which heart valve?

PMID- 1978912
TI  - Managing status epilepticus.

PMID- 1978913
TI  - Gene amplification directly from Guthrie blood spots.

PMID- 1978914
TI  - Mitochondrial mutation in fatal infantile cardiomyopathy.

PMID- 1978915
TI  - Detection of debrisoquine hydroxylation phenotypes.

PMID- 1978917
TI  - Medical rubber anaphylaxis.

PMID- 1978916
TI  - Proteinuria as complication of simvastatin treatment.

PMID- 1978918
TI  - Haematuria and proteinuria after thrombolytic therapy.

PMID- 1978919
TI  - Reduction of hypertension in hypovolaemia.

PMID- 1978920
TI  - Doxorubicin/methotrexate/fluorouracil in advanced pancreatic cancer.

PMID- 1978921
TI  - Cyclo (His-Pro) in nutritional supplements.

PMID- 1978922
TI  - Acute renal graft rejection after treatment with human growth hormone.

PMID- 1978923
TI  - Benign meningococcaemia: a rash diagnosis?

PMID- 1978924
TI  - Occupational infection among anaesthetists.

PMID- 1978926
TI  - Histamine2-receptor antagonists. Standard therapy for acid-peptic diseases (2)

PMID- 1978925
TI  - Role of arginine 180 and glutamic acid 177 of ricin toxin A chain in enzymatic
      inactivation of ribosomes.
AB  - The gene for ricin toxin A chain was modified by site-specific mutagenesis to
      change arginine 180 to alanine, glutamine, methionine, lysine, or histidine.
      Separately, glutamic acid 177 was changed to alanine and glutamic acid 208 was
      changed to aspartic acid. Both the wild-type and mutant proteins were expressed
      in Escherichia coli and, when soluble, purified and tested quantitatively for
      enzyme activity. A positive charge at position 180 was found necessary for
      solubility of the protein and for enzyme activity. Similarly, a negative charge
      with a proper geometry in the vicinity of position 177 was critical for ricin
      toxin A chain catalysis. When glutamic acid 177 was converted to alanine, nearby
      glutamic acid 208 could largely substitute for it. This observation provided
      valuable structural information concerning the nature of second-site mutations.

PMID- 1978927
TI  - Conditioning as a critical determinant of sensitization induced by psychomotor
      stimulants.
AB  - It is apparent that stimuli associated with psychomotor stimulants as well as
      opiates acquire the ability to elicit motor behaviors that probably reflect the
      acquisition and operation of incentive motivational processes. Such conditioning
      also appears to be a critical determinant of behavioral sensitization seen with
      repetitive administration of these agents. The conditioning of motor excitation
      to stimuli associated with psychomotor stimulants follows the principles of
      classical conditioning and is relatively long lasting. Dopaminergic mechanisms
      appear to be involved in the acquisition of such conditioned behaviors, since
      neuroleptics are effective blockers of the process. Dopaminergic blockade
      probably disrupts conditioning through several different mechanisms including
      attenuation of the conditioned and unconditioned excitatory properties of the CS
      and blockade of the US. DA blockade prevents stimuli associated with psychomotor
      stimulants from acquiring and subsequently generating positive affective
      motivational states that are reflected by increases in motoric output. While
      dopamine appears to be necessary for the formation of conditioned motor
      excitation, it is not critically involved in the expression of the conditioned
      effects. This seems to suggest that DA may serve only to modulate the formation
      of motivationally significant associations but is not involved in the expression
      of conditioned drug effects that may be mediated through DA-independent pathways.
      The amygdala and nucleus accumbens are two structures in the CNS involved in the
      acquisition of conditioned motor excitation. Interestingly, both of these brain
      regions are the recipients of mesolimbic DA input. Dopamine probably plays
      different roles in each region during the conditioning process. In the amygdala,
      mesolimbic DA may serve to modulate processes that attach emotional significance
      to environmental stimuli; further, DA may play a role in determining which
      stimuli gain access to structures afferent to the amygdala, including the nucleus
      accumbens. Dopamine in the nucleus accumbens, on the other hand, serves to
      determine which limbic inputs gain access to the motor pathways. In this way, DA
      in the nucleus accumbens may translate the motivational determinants of behavior
      that are mediated by limbic structures into biologically relevant actions.
      Understanding the mechanisms that determine the conditioning of drug effects to
      associated stimuli also has possible relevance for elucidating processes
      underlying addictive behaviors. For example, it has been proposed (Stewart et al.
      1984) that the acquisition of incentive motivational properties by stimuli
      associated with drugs determines the craving in addicts.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 1978928
TI  - HIV infection. Why the long latent period?

PMID- 1978929
TI  - The mitochondrial chaperonin hsp60 is required for its own assembly.
AB  - Heatshock protein 60 (hsp60) in the matrix of mitochondria is essential for the
      folding and assembly of newly imported proteins. Hsp60 belongs to a class of
      structurally related chaperonins found in organelles of endosymbiotic origin and
      in the bacterial cytosol. Hsp60 monomers form a complex arranged as two stacked 7
      mer rings. This 14-mer complex binds unfolded proteins at its surface, then seems
      to catalyse their folding in an ATP-dependent process. The question arises as to
      how such an assembly machinery is itself folded and assembled. Hsp60 subunits are
      encoded by a nuclear gene and translated in the cytosol as precursors which are
      translocated into mitochondria and proteolytically processed. In both intact
      cells and isolated mitochondria of the hsp60-defective yeast mutant mif4, self
      assembly of newly imported wild-type subunits is not observed. Functional pre
      existing hsp60 complex is required in order to form new, assembled, 14-mer.
      Subunits imported in vitro are assembled with a surprisingly fast half-time of 5
      10 min, indicative of a catalysed reaction. These findings are further evidence
      that self-assembly may not be the principal mechanism by which proteins attain
      their functional conformation in the intact cell.

PMID- 1978930
TI  - Hypoglycemic neurotoxicity in vitro: involvement of excitatory amino acid
      receptors and attenuation by monosialoganglioside GM1.
AB  - Rat cerebellar granule cells, when subjected to a glucose-free environment for 4
      h, developed extensive degeneration of neuronal cell bodies and their associated
      neurite network over the following 24 h. This neuronal damage was quantitated
      with a colorimetric assay using the metabolic dye 3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyl tetrazolium bromide. Hypoglycemic neuronal injury could be markedly
      reduced by the presence of both competitive (3-(+/-)-2-carboxypiperazin-4-yl)
      propyl-1-phosphonic acid) and non-competitive (phencyclidine) N-methyl-D
      aspartate receptor antagonists, but not by kainate/quisqualate preferring
      antagonists 6-cyano-7-nitroquinoxaline-2,3-dione and 6,7-dinitroquinoxaline-2,3
      dione. Glucose deprivation neuronal injury was also reduced by adding glutamate
      degrading enzymes to the incubation medium. Monosialoganglioside GM1, but not its
      asialo derivative (lacking sialic acid), was also effective in protecting against
      hypoglycemic neurodegeneration when included during the period of glucose
      deprivation. These results suggest that the neuronal injury to cerebellar granule
      cells resulting from glucose deprivation is mediated predominantly by activation
      of the N-methyl-D-aspartate type of excitatory amino acid receptor, perhaps
      through the action of endogenously released glutamate. Furthermore, the
      monosialoganglioside GM1, a member of a class of naturally occurring
      sialoglycosphingolipids, is able to attenuate this neuronal injury--as already
      observed for glutamate neurotoxicity and anoxic neuronal death in cerebellar
      granule cells. Gangliosides may thus prove to be of therapeutic utility in
      excitatory amino acid-associated neuropathologies.

PMID- 1978931
TI  - [Vecuronium bromide in pediatric anesthesia].
AB  - Ninety patients were included in a study to assess the clinical characteristics
      of vecuronium bromide used in children. The myorelaxant was administered to all
      patients using different routes. The use of vecuronium at a dose approximately
      equal to 1ED95 was characterised by a duration of action sufficient to allow its
      use in short operations; on the other hand, it also produced a long induction
      intubation interval and not optimal conditions in which to perform intubation.
      Conditions for intubation improved during induction via inhalation and there was
      a reduced induction-intubation interval compared to intravenous induction using
      the same dose of vecuronium. A further reduction in intubation time was obtained
      by increasing the dose from 50 to 150 micrograms/kg-1 together with an increased
      clinical duration of action. The "priming principle" technique also allowed
      intubation time to be shortened without variations in the duration of action
      provided a full dose of vecuronium, 100 micrograms/kg-1, was used. However, this
      was also associated with a notable incidence of adverse reactions. Of the various
      combinations examined, the most advantageous association of pre-dose and interval
      between doses was the association of a pre-dose of 10 micrograms/kg-1 and an
      interval of 4 min between doses. Lower doses countered the advantages of priming,
      whereas higher doses resulted in an increased number of adverse reactions without
      producing notable changes in the intubation time.

PMID- 1978932
TI  - The immunology of HIV disease and pregnancy and possible interactions.
AB  - HIV infection may impair a large portion of the human immune response. Infection
      of CD4+ T cells results in depletion of this population, leading to dysfunction
      of T-cell-dependent activities. Numerous other immune functions are directly or
      indirectly impaired, including the function of CD8+ T cells and decreases in
      total lymphocytes, IL-2 secretion, IL-2R expression, proliferative response to
      mitogens, NK activity, ADCC, and several other measures. Immune alterations seen
      in normal pregnancy include decreases in CD4 and T cells, the proliferative
      response to mitogen, IL-2 secretion, and NK activity. These changes are largely
      cellular and usually are not apparent clinically. Normal pregnant women are
      immunocompetent. When pregnancy is complicated by asymptomatic HIV infection, the
      obstetric outcome does not seem to be adversely affected. Preliminary studies
      show that the course of HIV disease may not be adversely affected in these women,
      but this matter is the subject of intense investigation.

PMID- 1978933
TI  - Student Research Award 1990. Catecholaminergic innervation of the inner ear.
AB  - Cochlear blood flow has been shown to be controlled, in part, by the sympathetic
      nervous system. We have used immunocytochemical staining for tyrosine hydroxylase
      (TH) to further demonstrate the extent of catecholaminergic innervation of the
      cochlea. Deeply anesthetized Mongolian gerbils were systemically perfused with
      phosphate-buffered saline, followed by 4% paraformaldehyde. The cochleae were
      dissected out and post-fixed for 3 hours in 4% paraformaldehyde. They were then
      incubated in anti-TH antibody and subsequently processed using the avidin-biotin
      immunoperoxidase method. Microscopic examination of whole-mounted tissue revealed
      many immunoreactive fibers on the spiral modiolar artery. TH-positive fibers have
      also been found on both radiating arterioles and radial collecting venules, which
      has not been previously reported. With innervation of these small vessels, blood
      flow in the cochlea may be segmentally controlled. We also further describe the
      organization of TH-positive fibers in the osseous spiral lamina.

PMID- 1978934
TI  - The effects of field stimulation on bovine mesenteric lymph node contractility.
AB  - In these studies isometric tension was recorded from isolated strips of bovine
      mesenteric lymph node capsule. The possible influence of intrinsic nerves on
      their contractile activity was examined using field stimulation and the
      pharmacology of the response was investigated. Over 75% of the tissues studied
      demonstrated regular spontaneous activity at a frequency of 3.9 +/- 0.2
      contractions/5 min under control conditions. Field stimulation at 2.8 and 32 Hz
      (pulse width = 0.3 ms, nominal voltage 60 V) produced frequency-dependent
      increases in the rate of this spontaneous activity associated with a raised
      baseline tension. These responses were not diminished on repeat stimulation under
      control conditions. The contraction frequency response to stimulation at 8 Hz was
      blocked completely in the presence of 1 microM tetrodotoxin, while the increase
      in baseline tension was reduced by over 80%, suggesting that field stimulation
      was activating intrinsic nerves. The responses to stimulation (8 Hz) were also
      greatly reduced by 10 microM phentolamine but were unaffected by 10 microM
      propranolol. These experiments suggest that intrinsic nerves can modulate the
      contractile activity of lymph node capsule acting, at least in part, through
      excitatory alpha-adrenoceptors. The possible functional significance of this is
      discussed.

PMID- 1978935
TI  - [Genomic sequences--a challenge. 1. Description of human genomic sequences and
      genetic identification methods].

PMID- 1978936
TI  - The teaching of organ pathology in European undergraduate education programs in
      medicine.
AB  - The European Society of Pathology has established a working group on the
      undergraduate teaching of pathology. At the IX European Congress of Pathology in
      Hamburg 1982 some general problems and opportunities regarding the teaching of
      pathology for undergraduate students in Europe were dealt with. We undertook to
      formulate the educational objectives of pathology for undergraduates and outlined
      the subject content necessary to achieve these objectives, how much time is
      necessary to teach pathology, and when during the medical course the teaching
      should take place. The results were published as an article in Path Res Pract
      178, 518-519, 1984. At the Xth European Congress in Athens 1985 we dealt with the
      teaching of general pathology in European undergraduate education program in
      medicine, and both subject content, time, place, pedagogics and the construction
      of a syllabus guide in general pathology were discussed and defined in detail.
      The results of this discussion were published in Path Res Pract 181, 365-369,
      1986. In two symposia in Porto we concentrated on the teaching of organ pathology
      as a subject of its own, apart from general pathology. This will be continued at
      the next congress in Ljubljana September 1-6, 1991.

PMID- 1978937
TI  - Effect of d-mannose on fimbriae of bacterial isolates from chicken carcasses.
AB  - Pseudomonad-like microbial isolates were obtained from commercially processed
      broiler chicken carcasses for use in experiments to determine if d-mannose would
      interfere with their ability to form pellicles and rims and prevent agglutination
      of blood and yeast cells. Inhibition of agglutination, rim formation, and
      pellicle formation would provide evidence that d-mannose acts on the fimbriae to
      prevent attachment of microorganisms to surfaces. Presence of 4% d-mannose in the
      growth medium interfered with the formation and stability of the pellicle in some
      isolates. The pellicles affected by d-mannose did not cover the entire surface
      and were easily dispersed. Addition of d-mannose did not prevent the formation of
      rims to the same extent it prevented pellicle formation, and it was concluded
      that d-mannose did not completely prevent growth of fimbriae. The addition of d
      mannose prevented the agglutination of 1% sheep blood, 1% horse blood, and yeast
      cells by interfering with the formation of fimbriae or the mechanism of
      attachment by fimbriae. These experiments provided evidence that d-mannose can be
      used to prevent attachment of isolates normally found on chicken carcasses to
      specific cell surfaces by occupying mannose-sensitive receptor sites on the cell.

PMID- 1978938
TI  - Allelic loss of chromosomes 16q and 10q in human prostate cancer.
AB  - Recent advances in understanding the molecular genetics of common adult tumors
      have indicated that multiple genetic alterations including the activation of
      oncogenes and the inactivation of tumor suppressor genes are important in the
      pathogenesis of these tumors. Loss of heterozygosity is a hallmark of tumor
      suppressor gene inactivation and has been used to identify chromosomal regions
      that contain these genes. We have examined allelic loss in the most common tumor
      in men, prostate cancer. Twenty-eight prostate cancer specimens have been
      examined for loss of heterozygosity at 11 different chromosomal arms including
      3p, 7q, 9q, 10p, 10q, 11p, 13q, 16p, 16q, 17p, and 18q. Fifty-four percent
      (13/24) of clinically localized tumors and 4 of 4 metastatic tumors showed loss
      of heterozygosity on at least one chromosome. Chromosomes 16q and 10q exhibited
      the highest frequency of loss of heterozygosity with 30% of tumors showing loss
      at these chromosomes. These data demonstrate that allelic loss is a common event
      in prostate cancer and suggest that chromosomes 16q and 10q may contain the sites
      of tumor suppressor genes important in the pathogenesis of human prostate cancer.

PMID- 1978939
TI  - An ancient, highly conserved family of cysteine-rich protein domains revealed by
      cloning type I and type II murine macrophage scavenger receptors.
AB  - Scavenger receptors have been implicated in the development of atherosclerosis
      and other macrophage-associated functions. The bovine type I and type II
      scavenger receptors are multidomain transmembrane proteins that differ only by
      the presence in the type I receptor of an additional, extracellular cysteine-rich
      C-terminal domain. The isolation of type I and type II receptor cDNAs from a
      murine macrophage cell line, P388D1, establishes the presence of mRNAs encoding
      both receptor types in a single cell. Their sequences are highly similar to the
      bovine cDNAs. Receptor type-specific cDNA probes map to a common locus on murine
      chromosomes 8, suggesting that a single gene encodes both mRNAs. The type I
      specific scavenger receptor cysteine-rich (SRCR) domain helps define a previously
      unrecognized family of remarkably well-conserved domains. Highly homologous SRCR
      domains (one, three, or four per polypeptide chain) are found in diverse secreted
      and cell-surface proteins from humans (e.g., CD5, complement factor I), mice (Ly
      1), and sea urchins (speract receptor).

PMID- 1978942
TI  - Effects of therapy on biology and kinetics of the residual tumor, Part A: pre
      clinical aspects. Proceedings of an international symposium. Vancouver, British
      Columbia, Canada, February 15-18, 1989.

PMID- 1978941
TI  - Identification and structural analysis of residues in the V1 region of CD4
      involved in interaction with human immunodeficiency virus envelope glycoprotein
      gp120 and class II major histocompatibility complex molecules.
AB  - The human CD4 molecule binds both human immunodeficiency virus envelope protein
      gp120 and class II major histocompatibility complex (MHC) molecules. We have
      studied a series of mutants in the region of amino acids 42-49 of CD4 for their
      ability to bind gp120, to interact with class II MHC, to enhance T-cell
      activation, and to bind a panel of anti-CD4 antibodies. The mutation Q40P (Gln40-
      --Pro) and the deletion d42-49 were found to disrupt most antibody epitopes in
      the V1 domain of CD4, suggesting major conformational changes, whereas mutants
      F43L, G47R, and P48S retained the binding of most of the anti-CD4 antibodies
      tested. The mutants d42-49, Q40P, F43L, and G47R lost both gp120 and class II MHC
      binding as well as the ability to enhance T-cell activation. In contrast, the
      mutation P48S affected neither gp120 binding, nor class II MHC binding, nor T
      cell activation. We conclude that within this region the binding sites for gp120
      and for class II MHC molecules overlap and that amino acids Phe43 and Gly47
      comprise an intimate part of both binding sites. These observations are
      consistent with a three-dimensional model of the V1 domain of CD4 that was
      developed in order to understand the structural basis for binding to CD4.

PMID- 1978940
TI  - Induction of specific clonal anergy in human T lymphocytes by Staphylococcus
      aureus enterotoxins.
AB  - The exotoxins produced by certain strains of Staphylococcus aureus are able to
      stimulate powerful polyclonal proliferative responses and to induce
      nonresponsiveness by clonal deletion of T lymphocytes expressing the appropriate
      T-cell antigen receptor V beta gene products. This paper examines the ability of
      S. aureus enterotoxins to modulate the responsiveness of human CD4+ T lymphocytes
      with defined antigen specificity. It was observed that certain S. aureus toxins
      were able to activate and induce anergy in hemagglutinin-reactive T cells
      expressing V beta 3+ elements. After exposure to S. aureus enterotoxins A, B, and
      D in the absence of antigen-presenting cells, the T cells failed to respond to
      their natural ligand presented in an immunogenic form, despite enhanced
      proliferation to exogenous interleukin 2. The S. aureus toxin-induced anergy was
      associated with modulation of T-cell membrane receptors; down-regulation of the T
      cell antigen receptor was concomitant with enhanced expression of CD2 and CD25.
      Interestingly, CD28 was increased only on stimulation, suggesting this protein
      may be differentially expressed by activated and anergic T cells. These results
      indicate that bacterial toxins are able to induce antigen-specific
      nonresponsiveness in human T cells, the application of which may be relevant in
      the regulation of T cells expressing a particular family of V beta gene products.

PMID- 1978943
TI  - HER-2/neu oncogene amplification and expression in breast and ovarian cancers.

PMID- 1978944
TI  - Molecular genetics of chromosome 21 and Down syndrome. Proceedings of the Sixth
      Annual National Down Syndrome Society Symposium. New York, New York, December 7
      8, 1989.

PMID- 1978945
TI  - Effects of tamoxifen and somatostatin analogue on growth of human medullary,
      follicular, and papillary thyroid carcinoma cell lines: tissue culture and nude
      mouse xenograft studies.
AB  - The knowledge that (1) the normal thyroid contains somatostatin, (2) polypeptide
      growth factors influence thyroid cell function, and (3) thyroid cells contain
      steroid hormone receptors prompted us to add somatostatin analogue No. 201-995
      (SMS) (5 ng/ml) and/or tamoxifen citrate (TAM) (5 mumol/L) to 7-day monolayer
      cultures (50,000 cells/well) of three separate human thyroid carcinoma cell
      lines: DR081 (medullary), WR082 (follicular), and NPA'87 (papillary). Results,
      tabulated as cell numbers/well (X10(5) on day 7, revealed that TAM inhibited
      growth of medullary and follicular cells and that TAM plus SMS inhibited growth
      of papillary cells. In vivo studies of subcutaneous tumor cell xenografts in nude
      mice have documented that TAM (5 mg subcutaneous pellet) significantly inhibits
      the growth of medullary implants. Flow cytometric DNA studies of medullary cell
      cultures demonstrated a reduced G2 + M phase with TAM treatment. For papillary
      cell implants, TAM plus SMS (5 micrograms subcutaneously, twice daily) did not
      suppress tumor growth. All three cell lines were negative for estrogen receptor;
      addition of estradiol (5 ng/ml) to medullary cell cultures neither stimulated
      replication nor reversed the inhibitory effects of TAM in vitro. We conclude that
      (1) TAM slowed the growth of a cell line of human medullary carcinoma, both in
      vitro and in vivo; (2) this effect was not reversed by estradiol; (3) TAM plus
      SMS inhibited replication of a papillary carcinoma cell line in vitro, but not in
      vivo; and (4) TAM alone and TAM plus SMS inhibited replication of cultures of a
      human follicular thyroid carcinoma cell line. TAM and SMS may be useful in
      treatment of some human thyroid carcinomas.

PMID- 1978946
TI  - The effect of somatostatin on 5-hydroxytryptamine release from a carcinoid tumor.
AB  - One of the major manifestations of the carcinoid syndrome is secretory diarrhea
      thought to be due to overproduction of 5-hydroxytryptamine (5-HT). Synthetic
      somatostatin analogues have proved to be clinically effective in controlling this
      diarrhea. We have established a continuous cell line from a human pancreatic
      carcinoid tumor that secretes 5-HT. We examined the ability of the somatostatin
      analogue, SMS 201-995, to inhibit 5-HT release in vitro. Tumor cells were exposed
      to SMS 201-995 (10(-6) mol/L), pentagastrin (10(-9) mol/L), acetylcholine (10(-5)
      mol/L), and isoproterenol (10(-5) mol/L) alone and in combination; 5-HT release
      was assayed with high pressure liquid chromatography. We found that pentagastrin
      (6.43 +/- 0.64 ng/ml), isoproterenol (20.24 +/- 2.17 ng/ml), and acetylcholine
      (12.39 +/- 1.10 ng/ml) each stimulated release of 5-HT compared to control values
      (4.38 +/- 0.42 ng/ml). SMS 201-995 significantly reduced release of 5-HT in
      response to isoproterenol and acetylcholine but did not inhibit the effect of
      pentagastin. These data suggest that different agents do not act through the same
      pathway to stimulate 5-HT release from human pancreatic carcinoid cells.

PMID- 1978947
TI  - Use of inhaled corticosteroids in patients with mild asthma.
AB  - A double blind, parallel group study was carried out to investigate the effect of
      inhaled budesonide in a moderate (200 micrograms) and a low (100 micrograms)
      twice daily dosage compared with the effect of placebo in 103 adults with mild
      symptomatic asthma. Subjects recorded peak expiratory flow (PEF), asthma
      symptoms, and beta 2 agonist consumption at home for a period of seven weeks (a
      one week run in and six weeks' treatment). Morning baseline PEF (around 80% of
      predicted normal) increased non-significantly to 88% with 200 micrograms
      budesonide daily and to 90% (p less than 0.05) with 400 micrograms, compared with
      81% with placebo. Evening PEF (around 94% of predicted normal) did not change
      significantly with active or placebo treatment. By comparison with placebo, there
      was a significant decrease in nocturnal asthma symptoms and beta 2 agonist
      consumption. The changes during the day were less pronounced and significant only
      for 400 micrograms budesonide daily. No significant differences between the two
      active treatments were detected. It is concluded that low doses of inhaled
      budesonide are effective in patients with mild symptomatic asthma, particularly
      for night time symptoms and early morning lung function. The early introduction
      of inhaled corticosteroids for patients with mild asthma and night time symptoms
      may improve their quality of life during the night and early morning.

PMID- 1978948
TI  - The HLA-D region-associated MS-susceptibility genes may be located telomeric to
      the HLA-DP subregion.

PMID- 1978949
TI  - The c-erB-2 protein.

PMID- 1978951
TI  - Persistent mullerian duct syndrome.
AB  - Persistent mullerian syndrome is rare. A case of phenotypically normal male with
      persistent mullerian structures that consisted of a bicornuate uterus, fallopian
      tubes, and upper third of the vagina is reported. These unusual structures were
      found in association with bilateral cryptorchidism and a right inguinal hernia,
      and were diagnosed while repairing the hernia in the neonatal period. The uterus
      and fallopian tubes were removed via laparotomy when the child was eighteen
      months old; at the same time a bilateral orchiopexy was performed. To avoid
      damage to the vas deferens, which lay in closely to the mullerian structures and
      could not be separated from the vaginal wall, a small segment of the upper third
      of the vagina was retained. The testicles, although normal on pathologic
      examination, have shown poor response to hormonal stimulation with human
      chorionic gonadotropin. Long-term follow-up for these patients is necessary
      because they have an increased risk of testicular tumors developing.

PMID- 1978950
TI  - Ultrastructural localization of c-erbB-2 gene product in transitional cell
      carcinoma of the urinary tract.
AB  - The c-erbB-2 gene product was demonstrated immunoelectron microscopically in
      human transitional cell carcinomas of the urinary tract. Two antibodies specific
      for the c-erbB-2 gene product were used: a polyclonal antibody directed to the
      intracellular domain and a monoclonal antibody recognizing an epitope in the
      extracellular domain. The immunoreaction with the polyclonal antibody was
      observed on cell membranes and the cytoplasmic area beneath membranes with
      particularly strong reaction on microvilli. The immune reaction with the
      monoclonal antibody was confined to cell membranes with a linear pattern.
      Amorphous deposits in the intercellular spaces were also immunoreactive with the
      monoclonal antibody directed to an extracellular epitope, suggesting that a part
      of the c-erbB-2 gene product may be released from the cancer cell membranes into
      the extracellular space.

PMID- 1978952
TI  - Nine DNA probes for detection of toxin and adhesin genes in Escherichia coli
      isolated from diarrhoeal disease in animals.
AB  - DNA gene probes specific for genes encoding heat labile enterotoxin (LTI), heat
      stable enterotoxins (STIa, STII), vero cytotoxins (VT1, VT2), and adhesins K88
      (F4), K99(F5), F41 and 987P(F6) were used to examine 873 isolates of E. coli from
      cases of diarrhoea (680 from pigs, 187 from cattle and six from sheep). A total
      of 188 were toxin gene positive and of these 84 belonged to the classical ETEC
      serogroups. Of the other 104 toxin gene positive strains, 80 hybridized with the
      VT2 probe of which 34 were from cases of porcine post-weaning diarrhoea belonging
      to serogroup 0138:K81 and 22 were untypable strains from cattle.

PMID- 1978953
TI  - [Echocardiographic control of treatment of mild hypertension with trimepranol].
AB  - Forty men with hypertension, diastolic BP lower than 14.66 kPa, were treated for
      six months with Trimepranol, 10 mg three times per day, with echocardiographic
      checking of changes of the cardiac minute output and the peripheral vascular
      resistance at rest and during an isometric load. In patients with a low baseline
      vascular resistance (group A, n = 20) a substantially better therapeutic effect
      was recorded than in patients with a markedly elevated peripheral resistance
      (group B, n = 11). Trimepranol is indicated in patients with a higher heart rate
      at rest and with a significant increase of the latter during isometric loading
      tests.

PMID- 1978954
TI  - [Periarteritis nodosa of the gallbladder--2. Surgical case reports].
AB  - P.n. of the gallbladder is discussed as isolated and systemic form according to
      the description and analysis of 2 cases. In the 1st case the disease remained
      restricted to the gallbladder and no further complications involving the vessel
      system appeared so far in the follow up (2 years). In the 2nd case the patient
      dies few days after the operation due to a systemic involvement. Literature
      survey reveals a nonuniform classification of angiitis. Nevertheless we have
      tried to assign (classify) to 2 above mentioned cases.

PMID- 1978955
TI  - [Neurohumoral aspects of the pathogenesis of hemorrhagic shock].

PMID- 1978956
TI  - Multiple forms of gamma-glutamyltransferase and lipoproteins.
AB  - The gamma-glutamyltransferase isoenzyme patterns originating from human serum and
      homogenates of liver, kidney, pancreas and intestine in the presence and in
      absence of isolated lipoproteins has been studied. On the basis of these results
      one can conclude that the distribution of a variety of gamma-glutamyltransferase
      activities obtained by the electrophoresis of blood serum is not a consequence of
      an existence of a large number of true isoenzymes, but of increased
      concentrations of lipoproteins which bind to the enzyme thus causing the
      appearance of gamma-glutamyltransferase in the region of the appropriate
      lipoproteins.

PMID- 1978958
TI  - First Asahikawa International Symposium on Brainstem Control of Posture and
      Movements. September 12-14, 1989. Asahikawa, Hokkaido, Japan. Proceedings.

PMID- 1978957
TI  - [Special edition of the 1989 Congress of German Orthopedists. Karlsruhe, October
      18-22, 1989. Proceedings].

PMID- 1978959
TI  - [Surgery in recurrence of undescended testes].
AB  - In the period from Jan. '80 to Dec. '87 at the Pediatric Surgical Clinic in
      Belgrade 119 patients were operated upon or 147 recurrencies of undescended
      testes; in 28 cases (23.52%) there were bilateral recurrences. 4 patients were
      twice unsuccessfully operated on at the same side. The authors analyse the causes
      of failures of orchiopexy; the proved mistakes were divided into four groups: a)
      Mistakes due to the undiscovering of the testis, b) unpreparation, or
      insufficiently preparated the testis from surrounding tissues, c) insufficiently
      shortening of the testis' way toward the scrotum, and d) mistakes being
      occasionally arised during the fixation of the testis into the scrotum. During
      the first unsuccessful operation 20 testes have atrophied, so that a
      reintervention consisted only in the exploration. In other cases the testis was
      placed into the scrotum regardless whether it was normal or hypotrophic. In two
      cases a Fowler-Stephens procedure was carried out, and in one case an
      autotransplantation of the testis was done. An improvement was found in 89 testes
      (60.57%), while 38 cases (25.85%) remained with the same characteristics, as they
      were in the course of our surgical interventions.

PMID- 1978960
TI  - Neuroleptic treatment after episode of neuroleptic malignant syndrome.

PMID- 1978961
TI  - Neuroleptic malignant syndrome (NMS) on neuroleptic withdrawal.

PMID- 1978962
TI  - The treatment of depression in the 1990s--a focus on moclobemide. A symposium.
      Lisbon, Portugal, 9-11 March 1989. Proceedings.

PMID- 1978963
TI  - A large-scale, office-based study evaluates the use of a new class of non
      sedating antihistamines. A report from CEN.
AB  - The two newest agents in the class of nonsedating antihistamines were studied in
      a wide variety of family practice patients. In a Phase IV, prospective,
      alternating sequence, open-label design, patients having allergic rhinitis (AR)
      were assigned to receive either astemizole (n = 659) or terfenadine (n = 639).
      The resultant treatment groups, typical of family practices, were comparable for
      demographics, signs and symptoms of allergic rhinitis, and clinical profile. The
      groups differed in that astemizole patients had a longer history of AR and a
      higher frequency of family history of AR. Patients who were treated for 3 to 8
      weeks were grouped for analyses. The frequency and severity of the signs and
      symptoms of AR and patient complaints decreased markedly in both groups. Self
      reported improvement in quality of life based on nine measures was the same for
      each group. No differences were seen between treatments when positive-rated
      outcomes were combined in the final overall assessment by physicians and
      patients. In rating the success of therapy, physicians' ratings of "excellent"
      and patients' ratings of "felt much better" were reported more frequently (P less
      than 0.05) for astemizole, while physicians' ratings of "good" and patients'
      ratings of "better" were reported more frequently (P less than 0.05) for
      terfenadine.

PMID- 1978964
TI  - Current report--HIV. AIDS at the crossroads: a report from the 1990 International
      Conference on AIDS--San Francisco.
AB  - Major scientific and clinical breakthroughs in HIV disease are rarely saved for
      the International Conference on AIDS. Nevertheless, this conference provides an
      opportunity for experts, providers, and patients to gain new information,
      exchange ideas, and assess progress. The Conference is also a public forum for
      political and social discussion and serves as a barometer of scientific and
      social trends as well. This year's conference featured refinements in clinical
      care, a deeper understanding of the epidemiologic trends, and a public awareness
      of the many political aspects of the AIDS epidemic. Contributions from family
      physicians and other primary care providers about problems they face and the
      family aspects of HIV need still greater prominence and exposure. Hopefully
      family physicians will use their expertise and report at future international
      conferences.

PMID- 1978965
TI  - Myoblast transfer therapy. Proceedings of a Muscular Dystrophy Association
      International Conference. June 10-12, 1989, New York, New York.

PMID- 1978966
TI  - Molecular markers for myoblast transplantation in GRMD.

PMID- 1978967
TI  - [The neurosurgical treatment of traumatic fronto-basal spinal fluid fistulas. 66
      cases (1982-1986)].
AB  - Between 1982 and 1986, 66 patients suffering from traumatic frontobasal CSF
      fistulas were treated neurosurgically i.e. via a transcranial approach. In 68% an
      additional transcranial space-occupying lesion a direct open endocranium and/or a
      large basal cerebral hernia were found. The cases and relevant findings are
      discussed, followed by deliberations on the points enumerated below: -
      diagnostic, especially neuroradiological advances --problems of indications for
      surgery --the problem of the best possible surgical approach Both cranial and
      rhinological approach have their pros and cons. Their indications agree only
      partly, so that the choice of the method depends especially on the individual
      pathology. Progress has been achieved in recent years both neurosurgically and
      rhinologically. Neurosurgical results have been improved upon, and postoperative
      complications after cranial approach are now rare. Essential factors, apart from
      selecting the best possible time for surgery, are: --adequate intracranial
      debridement --the use of a microsurgical technique, as well as application of a
      various brain-protective, measures as stated in this article. Further progress is
      fundamentally based on best possible mutual cooperation between the disciplines
      involved, paying increased attention in future to endocrinological problems.

PMID- 1978968
TI  - [Additional intra-abdominal injuries in multiple-traumatized patients with pelvic
      fractures. Difficulties in diagnosis and therapy].
AB  - Between 1.1. 1987 to 31.12. 1988 178 polytraumatized patients were treated with
      62 patients demonstrating pelvic fractures. In 58% of patients injured by rapid
      falls pelvic fractures were diagnosed compared to only 25% of all patients with
      traffic accidents. 22% of all polytraumatized patients suffered from
      intraabdominal injuries, with raise to 47% in patients with pelvic fractures. To
      avoid unnecessary laparotomies caused by questionable positive lavage
      ultrasonography is recommended because of its high accuracy and lack of any
      diagnostic morbidity. 27 of 29 patients with intraabdominal injuries underwent
      laparotomy. One patient with an isolated kidney rupture was treated
      conservatively and one patient died before operation. The most common
      intraabdominal lesion was rupture of liver in 52% and splenic injury in 10
      patients. Lesions of the intestine were diagnosed in 11 patients mostly in
      combination with parenchymal injuries. Concerning the therapeutical approach a
      conservative treatment is recommended in order to shorten time of operation in
      concern of the progressively increasing retroperitoneal hematoma. The overall
      mortality rate was 36%. Most common cause was direct injury of CNS in 14 patients
      of whom 6 patients suffocated during the first 24 hours. Unstable dislocated
      pelvic fractures were primary stabilized by external fixator which may help to
      avoid further progressive retroperitoneal hematoma.

PMID- 1978969
TI  - [Patellar and quadriceps tendon ruptures].
AB  - Ten cases of rupture of quadriceps tendon and seven cases of rupture of the
      patellar ligament were studied. All patients were reexamined. One must
      differentiate between rupture of the quadriceps tendon (tendon ruptures in
      elderly patients with degeneratively changed tendon in trivial trauma) and
      rupture of the patellar tendon (tendon rupture in younger patients with
      considerable trauma). All the patients were discussed with regard to accident
      mechanism, histology, underlying systemic and local diseases, therapy and
      results. There were good results in all patients with rupture of the patella
      tendon. In seven of the ten patients with quadriceps tendon rupture, we noted
      also good results. Three patients had residual pain and restricted motion and
      function of the knee. In two of these cases, diagnosis and reconstruction was
      delayed for months, the other patient had an infection of an implanted knee
      endoprosthesis in the injured knee.

PMID- 1978970
TI  - [Indication for, technic and results of reconstruction of the extensor apparatus
      in the treatment of patellar instability and patellar chondropathy].
AB  - Patella dislocation or subluxation is a common cause of internal derangement of
      the knee. Frequently they lead to lesions of the articular cartilage of the
      patella. More than one-hundred operative methods have been described for surgical
      correction of this condition and for treatment of the chondral damage, suggesting
      that none has been consistently successful. Long-term results of extensor
      mechanism reconstruction have been published by Turba et al. (26) advocating a
      numerical rating system with subjective and objective criteria for the follow-up
      control. We present our operative technique and results with extensor mechanism
      reconstruction in 54 cases by applying the above mentioned rating system. With a
      follow-up period from more than one year 39 patients were available for control.
      The results of proximal reconstruction (24 cases) were good and excellent in 20
      cases by subjective and in 23 cases by objective evaluation. The proximal and
      distal reconstructions (15 cases) showed subjective 13 and objective 14 patients
      with good and excellent results.

PMID- 1978971
TI  - [Fatigue fracture of the tibia following osteosynthesis. An interesting case].
AB  - Stress-fractures most often affect healthy bones, in the majority of cases the
      tibia. We report a case of a young man who had a stress-fracture 18 months after
      osteosynthesis of a lower leg-fracture. Under biomechanical aspects an
      oscillation-fracture is mostly probable because the angle of the fracture is
      exactly 45 degrees to the longitudinal axis of the tibia.

PMID- 1978972
TI  - [Intramedullary nailing of peri-prosthetic fractures following total knee joint
      replacement].
AB  - Based on positive experiences in similar operations of the said method, we report
      3 cases of periprosthetic fractures after total knee arthroplasty treated by the
      principle of intramedullary osteosynthesis. After preoperative X-ray-planning a
      shorted AO-medullar nail was positioned on the proximal site of the prostheses in
      combination with autogenous resp. homogeneous bone grafts located in the fracture
      area. In relation to other procedures the advantages of these compound
      osteosyntheses are undisturbed periosteal blood supply, correct alignment and
      consolidation of the fracture, early weight bearing and reliable cement fixation.
      They legitimate in our opinion the increased effort of partial revision
      arthroplasty.

PMID- 1978973
TI  - [Clostridium perfringens infection following intramedullary nailing of an open
      femur shaft fracture].
AB  - In a 47-year old patient, clostridial bacteraemia and local gas gangrene
      developed following osteosynthesis of a penetrating femoral fracture by a
      medullary nail. The operation had been performed in a post-injury interval of 14
      days. The first clinical symptoms did not appear until 6 days after surgery.
      Operative treatment by large local incisions, debridement and drainage with the
      medullary nail left in situ accompanied by administration of penicillin G
      resulted in recovery. In the case presented here, local haematoma and debris due
      to the osteosynthesis procedure had probably induced a proliferation of
      clostridia leading to gas gangrene. The delay in development of signs and
      symptoms and the benign appearance of the wound resulted in delay in early
      diagnosis and appropriate treatment of this potentially life-threatening entity.
      Ultrasound proved to be a valuable tool in the evaluation of local changes. Even
      in performed in an appropriate postinjury interval, medullary nailing bears a
      potential risk of inducing a clostridial infection, so that the indication must
      be very strict.

PMID- 1978974
TI  - [Results of magnetic resonance and computerized tomography studies of
      augmentation plastic surgery of the anterior cruciate ligament using carbon
      fibers. II].
AB  - 19 patients out of those described in part I were examined by MRI and CT. We
      quote MRI as an excellent new mean of imaging without exposure to ionising
      radiation which renders sufficient information about the internal knee-structures
      without surgical invasion. The signal density for the neoligament as well
      intraarticular as in the "over the top"-position gives evidence for the ingrowth
      of mesenchymal structures. The MRI diagnosis was proved by histological
      examination in 2 cases. Very good correspondence between clinic examination and
      the CT-images could be found. On top of that the tibial drilling holes could be
      shown in an excellent way. The CT-scan is a fine instrument to judge the
      postoperative state of the anterior cruciate ligament. The density measurement
      inside and outside the bone gives evidence for mesenchymal growth inside the
      carbon fibre structure and the existence of a new natural ligament.

PMID- 1978975
TI  - [Embolization therapy of a femoral hemangiolipoma with intra-osseous invasion].
AB  - The paper presents the case of a gigantic inoperable hemangiolipoma of the right
      upper leg with infiltration into femur. Performed embolization therapy resulted
      in satisfactory subjective and objective improvement.

PMID- 1978976
TI  - [Occupational accident when walking normally?].

PMID- 1978977
TI  - The role of beta-blockade therapy for ventricular tachycardia induced with
      isoproterenol: a prospective analysis.
AB  - Isoproterenol is sometimes required for ventricular tachycardia (VT) induction.
      However, the role of beta-blockade for treatment of such VT has not been
      critically assessed. The use of beta-blockade was evaluated prospectively in 14
      consecutive patients who required isoproterenol 2.4 +/- 1.3 (+/- S.D.)
      micrograms/min to induce sustained monomorphic VT (greater than 30 seconds, or
      requiring termination due to hemodynamic collapse) after a negative baseline
      study. The VT mechanisms were enhanced automaticity (group A, six patients),
      triggered automaticity (group B, three patients), and reentry (group C, five
      patients). Groups A and B had serial intravenous electropharmacologic tests with
      propranolol alone (0.2 mg/kg), verapamil alone (0.15 mg/kg), and propranolol plus
      verapamil, and group C had serial tests with propranolol alone, procainamide or
      quinidine (class Ia drug) alone, and propranolol plus a class Ia drug until VT
      could no longer be induced. All six patients in group A responded to propranolol
      alone. In group B, one patient responded to verapamil alone, and two patients
      responded to propranolol plus verapamil. In group C, three patients responded to
      propranolol alone, one patient responded to a class Ia drug alone, and one
      patient responded to propranolol plus a class Ia drug. During a follow-up of 7 to
      37 (17.9 +/- 10.7) (+/- S.D.) months, VT has not recurred in any patient. Three
      patients treated initially with propranolol alone have required substitution of
      amiodarone due to refractory congestive heart failure. In patients requiring
      isoproterenol for VT induction, beta-blockade alone appears to be effective in
      preventing reinduction of VT caused by enhanced automaticity. A heterogeneous
      response occurs when the VT mechanisms are triggered automaticity or reentry.

PMID- 1978978
TI  - Double-peaking circadian variation in the occurrence of sustained
      supraventricular tachyarrhythmias.
AB  - We studied 251 patients less than or equal to 65 years of age admitted for
      treatment of symptomatic supraventricular tachyarrhythmia to assess whether these
      arrhythmias begin evenly throughout the day or manifest circadian variation in
      occurrence. The arrhythmias included 152 episodes of atrial fibrillation, 50
      episodes of supraventricular reentry tachycardia, 30 episodes of atrial flutter,
      and 19 cases of ectopic atrial tachycardia. A total of 209 patients could tell
      the exact time their symptoms had started. In 38 of them (18%), the arrhythmia
      had begun between midnight and 6:00 AM, in 63 (30%) between 6:01 AM and noon, in
      46 (22%) between noon and 6:00 PM, and in 62 (30%) between 6:01 PM and midnight.
      This distribution differed significantly from uniform occurrence (chi square 8.7,
      p less than 0.05). Fifty patients were using beta-adrenoceptor blocking agents
      when the arrhythmia occurred. Compared with the other 159 patients, they had no
      morning surge of arrhythmias (20% versus 33.3% of episodes between 6:01 AM and
      noon), but instead a much higher incidence at night (34% versus 13.2% of episodes
      between midnight and 6:00 AM) (chi square 14.4, p less than 0.005). We conclude
      that the frequency of onset of sustained supraventricular tachyarrhythmias varies
      with the time of day, showing nearly equal peaks in the morning and in the
      evening and a trough at night. The modifying effect of beta-adrenoceptor blockage
      suggests that many morning arrhythmias are of adrenergic origin while other,
      probably vagal arrhythmogenic mechanisms, prevail at night.

PMID- 1978980
TI  - Neurohumoral activation in congestive heart failure.
AB  - This article reviews the evidence that congestive heart failure is accompanied by
      an increased plasma norepinephrine concentration and that this is due not only to
      a reduced tissue clearance of the substance but also to a marked increase in
      sympathetic nerve activity. It also reports data that indicate that the
      sympathetic activation is associated with an activation of the renin-angiotensin
      system and an increased plasma level of vasopressin. At which degree of
      congestive heart failure these phenomena become manifest is not clear, but some
      studies suggest that the sympathetic and renin-angiotensin systems may be normal
      in asymptomatic congestive heart failure but already somewhat activated when this
      condition reaches New York Heart Association class II. There is also evidence
      that this activation, though initially compensatory, is eventually responsible
      for a number of adverse cardiovascular effects that account for the negative
      relationship between this event and survival. Finally, the article discusses the
      inability of the increased plasma level of atrial natriuretic peptide that
      characterizes congestive heart failure to offset the adverse effects of the
      neurohumoral activation and the variable influence of drug treatment on this
      phenomenon. This is not impossible to achieve, however, because heart
      transplantation appears to rapidly normalize a major factor in the increased
      sympathetic activity observed before surgical intervention, that is, impairment
      of the arterial baroreflex.

PMID- 1978979
TI  - Effects of xamoterol on inotropic and lusitropic properties of the human
      myocardium and on adenylate cyclase activity.
AB  - The purpose of the present study was to characterize the effects of xamoterol in
      the human myocardium. In the presence of forskolin or milrinone, xamoterol
      increased isometric force of contraction, contraction velocity, and relaxation
      velocity in isolated, electrically driven preparations from human myocardium, but
      had no effect alone. There was no difference in the effect of xamoterol between
      right atrial myocardium and left ventricular myocardium from nonfailing (NF),
      moderately failing (NYHA II-III), and severely failing (NYHA IV) human hearts.
      The positive inotropic and lusitropic effects of isoprenaline were reduced
      depending on the severity of heart failure in left ventricular myocardium (i.e.,
      NF greater than NYHA II-III greater than NYHA IV). In the presence of
      norepinephrine, xamoterol produced negative inotropic effects similar to those of
      the beta-adrenoceptor antagonists pindolol and propranolol. Xamoterol alone had
      no effects on force of contraction, whereas pindolol and propranolol markedly
      reduced contractile force. In NYHA class IV, isoprenaline stimulated adenylate
      cyclase about twofold but xamoterol, like pindolol or propranolol, had no effect.
      Experiments with the beta 1- and beta 2-selective antagonists CGP 207.12A and ICI
      118.551, respectively, showed that the positive inotropic and lusitropic effects
      of xamoterol were mediated by beta 1-adrenoceptors. Consistently, xamoterol had a
      selectivity of 13.8 at beta 1-adrenoceptors as measured in radioligand binding
      experiments. It is concluded that xamoterol acts as a beta 1-adrenoceptor
      antagonist with a selectivity of 13.8 in human ventricular myocardium. The
      compound has an intrinsic sympathomimetic activity, as it produces beta 1
      adrenoceptor-mediated positive inotropic and lusitropic effects in the presence
      of forskolin. The beneficial effects of xamoterol in patients with heart failure
      could be due to prevention of the detrimental effects of norepinephrine such as
      beta 1-adrenoceptor downregulation of an increase of Gi (inhibitory guanine
      nucleotide binding protein).

PMID- 1978981
TI  - Medical management of chronic heart failure: inotropic, vasodilator, or
      inodilator drugs?
AB  - On the basis of pathophysiologic mechanisms, the medical therapy of today for
      chronic heart failure is reviewed. The advantages and disadvantages of the
      vasodilator drugs and the inotropic drugs are presented. Finally, the therapeutic
      value of the inodilator drugs, which combine the central myocardial effects of
      positive inotropic agents with those of peripheral vasodilators, is discussed. In
      particular, the orally available dopaminergic agents, such as ibopamine, which
      interact with beta-receptors in the heart (mediating a positive inotropic effect)
      as well as with dopaminergic receptors in the peripheral vessels (mediating a
      systemic vasodilator effect) and in the kidneys (potentiating the natriuretic
      effect of diuresis), seem to be an advancement in the modern medical therapy of
      chronic heart failure. Data are shown during long-term treatment with ibopamine,
      in which the sustained clinical benefit in heart failure was not diminished,
      despite a decrease of the adrenergic receptors in blood cells. Dopamine plasma
      concentration was permanently normalized during long-term treatment. The
      discrepancy between clinical improvement and the measured adrenergic
      downregulation may be due to the interference of the inodilator with
      neurohormonal systems at multiple sites and is probably independent of receptor
      activation. It is suggested that the biosynthesis of noradrenaline is improved by
      increasing intracellular dopamine transport.

PMID- 1978982
TI  - Efficacy of ibopamine in the treatment of heart failure.
AB  - Loss of myocardial contractility, reflexly enhanced vasoconstriction, and
      neuroendocrine excitation are the pathophysiologic hallmarks of low-output heart
      failure. Drugs that counter both consequences afford considerable therapeutic
      potential in retarding and perhaps even in staying the consequences of the
      syndrome. Ibopamine possesses such potential through its unique ability to
      stimulate both dopaminergic- and beta-adrenoreceptors in the heart and
      circulatory system. Stimulation of dopaminergic- receptors and beta 2
      adrenoreceptors results in vasodilatation in all regional vascular territories.
      beta 2-Adrenoreceptor agonist activity also affords mild positive inotropic
      activity in the heart, whereas stimulation of presynaptic dopaminergic- receptors
      (DA2) attenuates the increased sympathetic neural outflow. The drug also
      suppresses the renin-angiotensin-aldosterone system in addition to having a
      direct natriuretic activity. The pharmacodynamic effects of ibopamine, exerted
      through its metabolite epinine, are translated into measurable therapeutic
      benefits in patients with chronic heart failure. The increase in peripheral blood
      flow induced in all regional vascular territories, including the kidneys, is
      associated with increased cardiac output and stroke volume and reduction in left
      ventricular pressure work, wall stress, and myocardial oxygen consumption. Plasma
      norepinephrine, angiotensin, and aldosterone are also reduced, and renal sodium
      excretion is enhanced. These hemodynamic and neuroendocrine activities, which are
      not subject to tolerance during sustained administration of the drug, are
      accompanied by clinically significant improvement in symptoms, exercise
      tolerance, and the New York Heart Association classification of disability. More
      important, no proarrhythmic effects have been observed during sustained
      treatment, and the minimal side effects observed during long-term treatment
      enhance the safety profile of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1978983
TI  - Agricultural occupational and environmental health: policy strategies for the
      future--the scientific basis. Part III. Iowa City and Des Moines, Iowa, September
      17-30, 1988. Proceedings.

PMID- 1978984
TI  - National survey of ethical issues presented to drug information centers.
AB  - Whether and how drug information centers respond to calls from the public that
      involve ethical issues was studied. A survey describing six ethical dilemmas
      typical of those presented by calls from the public was mailed to pharmacists in
      154 drug information centers to see how the questions would be handled. Centers
      that had written policies governing responses to questions with ethical
      implications were asked to submit those policies. One hundred twenty-six centers
      (82%) responded to the survey; of these, 81 (64.3%) answered questions from the
      public. There were no significant differences in characteristics between centers
      that did and did not respond to public calls. The case analyses, completed only
      by pharmacists in centers that responded to public calls, covered such issues as
      invasion of privacy, social responsibility, personal liability, and interference
      with the patient-physician relationship. Respondents exercised a wide degree of
      discretion in determining if they would answer a question; for example, while
      only 4% would not answer a question concerning the efficacy of a weight-loss diet
      patch, 77% reported they would not respond to a caller asking for information on
      drugs that could interfere with the results of a polygraph test. Although
      respondents often cited institutional policy as the reason for failing to respond
      to a question, none submitted a copy of such a policy. The pharmacists' responses
      indicated a high degree of moral and social sensitivity; nonetheless, written
      policies should be developed to assist drug information center staff members in
      handling questions that have ethical implications.

PMID- 1978985
TI  - Somatic mosaicism at the Duchenne locus.
AB  - Results of testing a family for carrier status and prenatal diagnosis for
      Duchenne muscular dystrophy (DMD) are best explained by somatic mosaicism in the
      maternal grandfather. This genetic situation was identified using segregation
      analysis of intragenic DNA polymorphisms, a serum creatine phosphokinase assay,
      and physical examination of the patients. This event at the DMD locus represents
      one more potential source of error in carrier testing and prenatal diagnosis.

PMID- 1978986
TI  - Spondyloepiphyseal dysplasia, mild autosomal dominant type is not due to primary
      defects of type II collagen.
AB  - A mild autosomal dominant form of spondyloepiphyseal dysplasia (SED) is present
      in several generations of a South African family of English stock. This phenotype
      differs from that of any other previously described. Although type II collagen
      defects have been found in some families with SED congenita, the phenotype in our
      family showed discordant segregation with COL2A1 gene associated restriction
      fragment length polymorphisms (RFLPs), the markers for the structural locus of
      type II collagen. It is evident that the SED group of disorders is heterogeneous.

PMID- 1978987
TI  - Some mechanistic insights into opioid tolerance.

PMID- 1978988
TI  - Differential cross-tolerance between intrathecal morphine and sufentanil in the
      rat.
AB  - By means of a subcutaneously implanted osmotic pump, groups of rats received a
      constant-rate (1 microliter/h), 7-day intrathecal infusion of saline or one of
      two mu opioid agonists: sufentanil (0.6 nmol/h) or morphine (20 nmol/h). These
      concentrations of morphine and sufentanil yielded a comparable near maximal hot
      plate response latency on day 1 of the infusion. On day 7, the magnitude of
      tolerance was assessed in each group by establishing intrathecal dose-response
      curves and ED50 values for sufentanil and morphine given as a bolus injection.
      Each infused animal was used for a single bolus injection. In all cases, infusion
      with the opioid resulted in a rightward shift (increase in ED50) for both
      morphine and sufentanil as compared to saline-infused animals. The magnitude of
      the shift, however, was different for the two drugs. Thus in morphine-infused
      rats, the morphine ED50 increased as compared to saline-infused animals by a
      factor of 44, whereas the sufentanil ED50 shifted by a factor of 10. In
      sufentanil-infused animals, the respective shifts in the morphine and sufentanil
      ED50 values were increased by a factor of 9 and 3, respectively. Thus, a
      significantly greater shift as compared to saline-infused animals was observed in
      morphine-infused than in sufentanil-infused animals. Conversely, regardless of
      the opioid to which the animal was exposed, morphine-tested animals showed a
      greater rightward shift than did sufentanil-tested animals.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1978989
TI  - Pharmacology of intrathecal adrenergic agonists: cardiovascular and nociceptive
      reflexes in halothane-anesthetized rats.
AB  - The effects of intrathecally administered adrenergic agonists (alpha-1
      methoxamine, alpha-2-dexmedetomidine, clonidine, and ST-91, beta-isoproterenol)
      on nociceptive (tail-flick reflex) and cardiovascular changes (blood pressure and
      heart rate) evoked by immersing the tail in 53 degrees C water were examined in
      rats anesthetized with halothane (0.75%) and in which intrathecal catheters had
      been chronically implanted. Administration of intrathecal alpha-2, but not alpha
      1 or beta agonists, produced a dose-dependent block of the tail-flick and evoked
      cardiovascular responses with the order of activity being as follows:
      dexmedetomidine greater than clonidine greater than ST-91 much greater than
      methoxamine greater than or equal to isoproterenol. These effects were readily
      reversed by the alpha-2 antagonist idazoxan. Intravenously administered
      dexmedetomidine at a dose that is active when given intrathecally (0.33
      micrograms) was without effect on either the tail-flick or the evoked
      cardiovascular responses. Without drugs, the halothane MAC was 1.23 +/- 0.07%. In
      the presence of intrathecally administered dexmedetomidine (0.33 micrograms), the
      MAC was significantly reduced to 0.9 +/- 0.09%. The intrathecal administration of
      alpha-2 agonists resulted in a rapid decrease in resting blood pressure and heart
      rate with the magnitude of hypotension being as follows: dexmedetomidine greater
      than clonidine greater than ST-91. These data suggest a potent spinal alpha-2
      receptor-mediated modulation of somatomotor and autonomic responses to pain.

PMID- 1978990
TI  - Antinociceptive interaction between opioids and medetomidine: systemic additivity
      and spinal synergy.
AB  - The antinociceptive interaction on the tail flick (TF) and hot plate (HP) tests
      between opioid analgesics and medetomidine after intravenous (iv) or intrathecal
      administration were examined by isobolographic analysis. Male Sprague-Dawley rats
      received fixed ratios of medetomidine to morphine, fentanyl, and meperidine of
      1:10 and 1:30, 10:1, and 1:3, respectively, by iv administration or 10:1, 3:1 and
      10:1, and 1:3 by intrathecal administration, respectively. Data were expressed as
      the percentage maximal possible effect (%MPE). The A50 (dose producing 50% MPE)
      for each drug or drug combination was determined from the dose-response curve.
      Isobolographic analysis revealed that the effect of medetomidine combined with
      fentanyl, morphine, or meperidine was additive after iv administration. The
      intrathecal administration of combinations of medetomidine with the opioids
      produced a synergistic antinociceptive effect in the TF but not HP test. These
      data confirmed that the interaction between medetomidine and opioids in producing
      antinociception may be additive or synergistic, depending on the route of
      administration, drug ratio administered, and level of processing of the
      nociceptive input (i.e., spinal vs. supraspinal). Moreover, these results were
      consistent with a spinal role for alpha-2 adrenoceptors in mediating
      antinociception. The authors suggest that the interaction between the opioid and
      alpha-2 adrenergic receptors occurs within the spinal cord.

PMID- 1978991
TI  - [32nd National Congress of Anesthesia-Resuscitation. 22-24 September 1990.
      Abstracts].

PMID- 1978992
TI  - Atherosclerosis II: Recent Progress in Atherosclerosis Research. The Second
      International Conference on Atherosclerosis. Towada, Japan, 1989. Proceedings.

PMID- 1978993
TI  - Scientific Issues of the Next Century: Convocation of World Academies.
      Proceedings of an international conference. Bologna, Italy, October 17-18, 1989.

PMID- 1978994
TI  - Central and Peripheral significance of Neuropeptide Y and its Related Peptides. A
      conference. Baltimore, Maryland, April 2-4, 1990. Proceedings.

PMID- 1978995
TI  - Neuropeptide Y and central cardiovascular regulation. Focus on its role as a
      cotransmitter in cardiovascular adrenergic neurons.

PMID- 1978996
TI  - Neuropeptide tyrosine in the cardiovascular system.

PMID- 1978997
TI  - Regulation of neuropeptide Y gene expression in rat brain.
AB  - NPY mRNA expression was studied in rat brain using in situ hybridization and RNA
      blot analysis. Transsynaptic regulation of NPY gene expression was specifically
      studied in caudate-putamen and frontoparietal (somatosensory) cortex of rats with
      unilateral lesion of midbrain dopamine neurons and in sham-injected animals. NPY
      mRNA expression in these two brain regions and the regulation of midbrain
      dopamine neurons were compared with that of SOM, PPT, CCK and GAD mRNA
      expression. Neurons expressing NPY and SOM mRNA showed a similar distribution and
      the expression of both NPY and SOM appears to be regulated by dopamine in a
      similar fashion. Following a unilateral dopamine deafferentation, the numerical
      density of both NPY and SOM mRNA expressing neurons almost doubled in the
      lesioned rat caudate-putamen with no change in the average grain density over
      positive neurons. Hence, in the intact caudate-putamen dopamine appears to
      normally suppress expression of these two neuropeptide genes. An activation of
      both NPY and SOM mRNA expression in many non- or low-expressing neurons is seen
      when the level of dopamine is decreased. In the frontoparietal cortex, on the
      other hand, dopamine appears to stimulate NPY and SOM gene expression. RNA blot
      analysis shows clear-cut changes of NPY mRNA levels in both caudate-putamen and
      frontoparietal cortex consistent with the changes observed using in situ
      hybridization. No evidence was found for a change in CCK mRNA expression by the
      dopamine deafferentation, while PPT mRNA expression decreased in the deafferented
      caudate-putamen. Consequently, dopamine exerts dissimilar effects on the
      expression of different neuropeptide genes, that in turn do not respond in the
      same way in different brain regions. Indirect evidence is also presented
      indicating that dopamine regulates NPY mRNA expression in a subpopulation of
      neurons that possibly also express GAD mRNA, both in caudate-putamen and in
      frontoparietal cortex.

PMID- 1978998
TI  - Ultrastructural localization of neuropeptide Y in the hypothalamus.
AB  - Immunoreactive NPY neurons are widely distributed in the hypothalamus of several
      mammalian species. In the rat, dense NPY fiber networks are found in the
      paraventricular, suprachiasmatic and arcuate nuclei. NPY-containing cell bodies
      are mostly found in the arcuate nucleus. Studies performed at the electron
      microscope level clearly indicate that NPY is concentrated in dense core vesicles
      in the cytoplasm of cell bodies as well as in terminals. Only a small percentage
      (about 20%) of the NPY endings are making synaptic contacts with nerve processes,
      especially dendrites. These ultrastructural data suggest that NPY might play a
      neurotransmitter/neuromodulator role. NPY has been shown, when injected into
      hypothalamic areas, to exert a variety of effects, including modifications in
      food intake, energy balance and pituitary secretion. In an attempt to define the
      exact role of NPY in hypothalamic functions, we have designed experiments to
      study the interactions of NPY with other neurotransmitter systems. In the
      suprachiasmatic nucleus, both NPY and 5-HT terminals have been shown to establish
      synaptic junctions sometimes with the same neurons. Occasionally, axoaxonic
      junctions between these two types of endings have been observed. These results
      suggested that both 5-HT and NPY might be involved in the complex regulation of
      circadian rythms. In the arcuate nucleus, nonsynaptic appositions between 5-HT
      nerve endings and NPY-containing neurons were demonstrated. In this nucleus,
      direct appositions between TH- and NPY-containing neurons were also detected.
      These appositions were of axosomatic, axodendritic or axoaxonic types. Since it
      has been demonstrated that arcuate NPY neurons are projected to other
      hypothalamic areas, such as the paraventricular and dorsomedial nuclei, it might
      be speculated that arcuate 5-HT/NPY and catecholamines/NPY interactions might be
      involved in regulation of behavior and neuroendocrine functions.

PMID- 1978999
TI  - The Booroola F gene mutation in sheep is not located close to the FSH-beta gene.
AB  - A cDNA probe for the beta subunit of bovine FSH (FSH-beta) detects multiple
      restriction fragment length polymorphisms (RFLPs) in sheep genomic DNA consistent
      with an insertion/deletion polymorphism around the FSH-beta locus. The presence
      of the insertion/deletion was confirmed by screening over 100 individuals with
      two restriction enzymes detecting RFLPs. All individuals showed the same patterns
      of fragments with both enzymes. A partial restriction map of the FSH-beta gene in
      sheep suggests that the insertion/deletion is approximately 2 kb in size and
      located downstream from the third exon. Individual DNA samples were analysed from
      two flocks where the Booroola F gene is known to be segregating. Individuals that
      were heterozygous for the F gene were shown to be homozygous for one or other of
      the two alleles. Genetic recombination between the FSH-beta locus and the F gene
      was observed in four pedigrees and there was no evidence that the
      insertion/deletion is closely linked genetically to the Booroola F gene. A major
      gene transcript of 2.2-2.3 kb was detected on Northern blots of sheep RNA.
      Neither the insertion/deletion polymorphism nor the presence of the F gene
      appeared to influence the size of the FSH-beta gene transcript.

PMID- 1979000
TI  - Hypomagnesemia in chronic obstructive lung disease: effect of therapy.
AB  - In 95 patients with severe chronic airway obstruction (FEV1 33.2 +/- 12% of
      predicted; mean +/- SE), we investigated whether drug therapy had any influence
      on serum Mg levels. 11/95 patients had a serum Mg less than 1.45 mEq/l (lower
      normal limit). Multiple-regression analysis showed that the use of diuretics was
      associated with a significantly lower serum Mg level (1.59 +/- CI 0.06 mEq/l vs.
      an adjusted mean of 1.71 mEq/l; F = 11, 2, p less than 0.001). There was a
      significant negative correlation between serum Mg and the length of oral steroid
      therapy (1.64 +/- CI 0.02 mEq/l for less than 24 months of therapy vs. 1.52 +/-
      CI 0.06 mEq/l for greater than 24 months of therapy; F = 7, 3, p less than
      0.005). No effect of theophylline, inhaled steroids or beta 2-agonists on serum
      Mg was observed. Because of potential negative effects of hypomagnesemia on
      respiratory function, routine serum magnesium determination is recommended in
      patients with chronic obstructive lung disease taking diuretic drugs or
      corticosteroids.

PMID- 1979001
TI  - Effects of dopamine D-1 and D-2 antagonists on decision making by rats: no
      reversal of neuroleptic-induced attenuation by scopolamine.
AB  - The effects of the dopamine (DA) D-1 antagonist SCH 23390 and the D-2 antagonists
      haloperidol and sulpiride on decision making in thirsty rats were investigated.
      The problem given to the rats was to choose between two behaviours, locomoting or
      lever-pressing, in order to obtain rewards (water). SCH23390 and haloperidol dose
      dependently reduced the number of rewards obtained. However, only minor effects
      were seen on the decision making parameters. DA is thus important for initiation
      and/or performance of learned behavioural acts, not for information sampling and
      processing leading to the decision of which behaviour to perform. There were no
      differences between D-1 and D-2 antagonism in this respect. After sulpiride, no
      significant effects were observed. A specific behavioural prolife obtained by
      extinction was not mimicked by any of the doses of neuroleptics tested. It has
      previously been shown that performance per se of the two behavioural options used
      in the task can be reinstated by scopolamine after haloperidol attenuation.
      However, when these options had to be organized into functional sequences to
      reach a goal, haloperidol-induced attenuation could not be counteracted by
      scopolamine.

PMID- 1979002
TI  - Alpha-1 adrenergic receptor binding and adrenergic-stimulated cyclic AMP
      production in rat cerebral cortex after chronic lithium treatment.
AB  - Administration to rats of dietary lithium for 30 days was followed by evaluation
      of alpha-1 adrenergic receptor binding and of adrenergic-stimulated cyclic AMP
      (cAMP) accumulation in rat cerebral cortex. Chronic lithium treatment did not
      alter the binding characteristics of [3H]prazosin or the proportion of alpha-1
      adrenergic receptor subtypes distinguished by chlorethyl-clonidine (CEC)
      pretreatment in rat cerebral cortical membranes. Accumulation of cAMP in cortical
      slices incubated with adrenergic agonists was unaffected in lithium-treated rats.
      These results demonstrate that chronic lithium treatment-induced reduction of
      norepinephrine (NE)-stimulated phosphoinositide (PI) hydrolysis (Casebolt and
      Jope, 1987) is not due to changes in the alpha-1 adrenergic receptor and is more
      sensitive to in vivo lithium treatment than is adrenergic-stimulated cAMP
      accumulation.

PMID- 1979004
TI  - Effects of constant light and darkness on the intrapineal neurons of golden
      hamsters, stained for tyrosine hydroxylase. A morphometric analysis.
AB  - Tyrosine hydroxylase (TH)-positive neurons (TH neurons) were found in the pineal
      gland of golden hamsters. To examine possible relations between TH neurons and
      environmental light, we kept male animals under constant light (LL) and darkness
      (DD) for a week, and morphometrically compared the number, size, and
      immunoreactivity of TH neurons with those of control animals kept under 12L/12D
      (LD), using an image processor, Nexus 6400. In LL animals, the number of TH
      neurons/mm2 of pineal tissue and each cell area were decreased, and
      immunoreactivity to TH was less than in LD animals. In DD animals, the number of
      TH neurons and each cell area were increased, and immunoreactivity decreased
      slightly. These data suggested that environmental light affected the TH neurons,
      and the amount of TH in the neurons would be decreased by LL, but increased by
      DD.

PMID- 1979003
TI  - Effect of serotoninergic drugs on stress-induced hyperthermia (SIH) in mice.
AB  - 8-OH-DPAT (2.5-10 mg/kg) and buspirone (10 mg/kg) but not 5,7-DHT (200
      micrograms/mouse), pCPA (75 and 150 mg/kg, three times), ritanserin (0.1 and 0.2
      mg/kg), LY 53857 (1.5 and 3 mg/kg), GR 38032 F (0.1-100 micrograms/kg), TFMPP (5
      and 20 mg/kg) and mCPP (2.5 and 5 mg/kg) antagonized the rise in body temperature
      that occurs to the last mice removed from their group housing, which was termed
      as stress-induced hyperthermia (SIH). Ro 15-1788, at a dose which blocked the
      effect of diazepam on SIH, did not reverse the anxiolytic effect of buspirione.
      Instead, when cerebral 5-HT content was reduced to 50% by 5,7-DHT-induced lesion,
      the effect of buspirone on SIH was decreased. TFMPP 5 mg/kg did not shorten
      significantly the onset of SIH as could have been expected by an anxiogenic drug,
      while the dose of 20 mg/kg did not modify the pattern of SIH at all. The lower
      dose of TFMPP evoked a hyperthermic and the higher a hypothermic response.

PMID- 1979005
TI  - Neuropharmacological and clinical aspects of alcohol withdrawal.
AB  - Abnormalities in the function or activity of several neurotransmitter systems
      have been demonstrated after acute and chronic, exposure to alcohol, and in
      alcohol withdrawal. The changes can be divided into alterations in function of
      inhibitory and excitatory systems. Inhibitory dysfunction is indicated by reduced
      gamma-aminobutyric acid and alpha-2-adrenoceptor activity. In conjunction with,
      and exacerbating this, is increased activity of excitatory systems, perhaps the
      most significant of which is the probable potentiation of N-methyl-D-aspartate
      activity by depletion of magnesium. There is additional, and possibly secondary,
      overactivity of catecholamine and corticotropin releasing factor neuronal
      systems. Other, less specific changes include increased numbers of calcium
      channels, which would increase neuronal excitability. The evidence for these
      changes is presented, and the implications for new treatment regimes for alcohol
      withdrawal are discussed.

PMID- 1979006
TI  - Experimental Salmonella typhimurium infections in rats. III. Transfer of immunity
      with primed lymphocyte subpopulations.
AB  - The protective effect of primed lymphocytes against a lethal dose of Salmonella
      typhimurium was studied in athymic and euthymic LEW rats. Primed lymphocytes were
      obtained by inoculating euthymic and thymus-grafted animals with a non-lethal
      dose of Salmonella typhimurium. Four weeks after the infection, spleen
      lymphocytes were separated by panning technique and antibody-coated magnetic
      microsphere separation using antibodies to pan T and pan B lymphocytes and
      subsequent sorting in a fluorescence activated cell sorter by means of monoclonal
      antibodies against CD4+ and CD8+ cells. Euthymic and athymic rats were injected
      with different doses of primed pan B, pan T, CD4+ and CD8+ T lymphocytes before
      inoculation with a lethal bacterial dose. Most of the animals treated with pan B,
      pan T or CD8+ cells died within two weeks. After treatment with primed CD4+
      cells, only six of 39 animals died. Doses as low as 10(4) cells from both
      euthymic or thymus-grafted animals were effective, and athymic and euthymic
      recipients survived equally well. Four weeks after the infection both athymic and
      euthymic animals housed very few bacteria and had high antibacterial antibody
      titres. The percentages of splenic and lymph node CD4+ cells in the athymic rats
      were comparable to those found in the euthymic animals. The study shows that
      primed CD4+ lymphocytes even in very low doses are able to induce immunity
      against a Salmonella typhimurium infection.

PMID- 1979007
TI  - Expression of the insulin-like and platelet-derived growth factor genes in human
      uterine tissues.
AB  - The human uterus repeatedly exhibits cyclic biochemical and cytological changes
      during the reproductive period of life. These changes are the result of a well
      characterized endocrine network involving the hypothalamus, pituitary, and ovary.
      The exact nature of the mechanism(s) by which the sex steroids act on the uterus
      remains to be elucidated. Possible local mediators of hormonal action on the
      uterus include polypeptide growth factors. Using the method of RNA transfer blot
      hybridization, we have analyzed tissue samples from the cycling human endometrium
      and tissue samples of human myometrium and myometrial benign tumor (leiomyoma)
      for the presence of platelet-derived growth factor (PDGF) and insulin-like growth
      factor (IGF) RNA. All the uterine tissues examined possessed RNA for PDGF-B chain
      and IGF-I and -II. Two transcripts were observed for PDGF-B chain, four were
      observed for IGF-I, and eight were observed for IGF-II. Overall, the relative
      abundance of PDGF-B chain RNA was consistent in all of the uterine tissues
      examined. In contrast, IGF RNA relative abundance varied. IGF-I RNA was highest
      in late proliferative stage endometrium, and IGF-II RNA was highest in early
      proliferative stage endometrium. Both IGF-I and IGF-II RNAs were greater in
      amount of leiomyoma than in myometrium. The increased IGF-I RNA in late
      proliferative-stage human endometrium correlates with the known elevation of
      estradiol secretion by the ovary and the increased concentration of uterine
      estradiol receptors during this stage of the menstrual cycle.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1979008
TI  - Restriction fragment length polymorphism (RFLP) analysis in wheat. I. Genomic DNA
      library construction and RFLP analysis in common wheat.
AB  - To develop detailed linkage maps of restriction fragment length polymorphism
      (RFLP) sites in wheat chromosomes, it was necessary to construct a genomic DNA
      library and to characterize the clones obtained. Forty-nine per cent of the
      clones were of single or low copy number per genome. With 91 clones of this
      class, as probes, and with two to four restriction endonucleases, for DNA
      digestion, RFLPs were examined among eight common wheats and a single emmer
      wheat. About 20% of the probes, and 13% of the probe-enzyme combinations revealed
      genetic polymorphism among the common wheats. DNA deletions account for most of
      the genetic differences among these wheat genomes. Based on the RFLP data,
      phylogenetic distances among the nine polyploid wheats were estimated, and a
      dendrogram showing the genetic relationships among them was constructed.

PMID- 1979009
TI  - Cardiovascular effects of doxacurium, pancuronium and vecuronium in anaesthetized
      patients presenting for coronary artery bypass surgery.
AB  - The cardiovascular effects of bolus doses of doxacurium 0.037 mg kg-1 were
      compared with those following equipotent doses of pancuronium (0.09 mg kg-1) and
      vecuronium (0.075 mg kg-1) and with those following high-dose doxacurium (0.075
      mg kg-1), in patients with coronary artery disease. Anaesthetic technique
      comprised premedication with lorazepam, papaveretum and hyoscine, induction with
      diazepam, fentanyl, thiopentone, atropine and suxamethonium, and the trachea was
      intubated. At least 20 min later, during stable nitrous oxide in oxygen
      anaesthesia, a single bolus of neuromuscular blocking drug was administered and
      the effects measured at 1, 5 and 10 min. There was a small decrease in heart rate
      following doxacurium 0.075 mg kg-1, but no other significant or dose-related
      changes in mean heart rate, arterial pressure or cardiac index with doxacurium.
      Similar results were found following vecuronium, but the reduction in heart rate
      was more pronounced. In contrast, significant increases in mean arterial
      pressure, heart rate and cardiac index occurred after pancuronium.

PMID- 1979010
TI  - Use of post-tetanic count in assessment of a repetitive vecuronium-induced
      neuromuscular block.
AB  - In order to evaluate the use of the post-tetanic count (PTC) method during
      repetitive administration of vecuronium, we studied 20 patients allocated
      randomly to one of two groups: 10 patients received droperidol-fentanyl
      anaesthesia (control group); 10 other patients were given droperidol-fentanyl
      anaesthesia modified subsequently by addition of 0.5% isoflurane (isoflurane
      group). Before tracheal intubation, a bolus dose of vecuronium 0.08 mg kg-1 was
      given i.v. followed by repeated doses of 0.03 mg kg-1. The twitch response of
      adductor pollicis was recorded after supramaximal stimulation of the ulnar nerve
      at the wrist using a Myograph 2000 neuromuscular transmission analyser. In the
      control group, a close correlation was found between PTC and time to first
      reaction to train-of-four (TOF) nerve stimulation. This relationship was
      unchanged when comparing the bolus dose and each of eight consecutive maintenance
      doses. Further, the degree and the duration of intense block were unchanged after
      each of the eight maintenance doses. In the isoflurane group, the relationship
      between PTC and time to first reaction to TOF stimulation remained unchanged
      after addition of isoflurane. However, isoflurane caused a significant
      prolongation of the duration of intense block and a corresponding lower PTC in
      all patients. We conclude that PTC is a reliable method to evaluate intense
      neuromuscular block caused by vecuronium, even after repetitive administration of
      the drug and in combination with 0.5% isoflurane.

PMID- 1979011
TI  - Multiple endocrine neoplasia type 3: three cases with mucosal neuromata.
AB  - Three female patients (ages 10, 18 & 25 years) with multiple endocrine neoplasia
      type 3 are reported. They had all characteristic facial appearances, with mucosal
      neuromata, rubbery swollen lips, tubercles on the tongue and eversion of the eye
      lids. Clinical signs and symptoms appeared to be progressive with increase in
      age, suggesting the importance of the correct diagnosis and early evaluation of
      endocrine function leading to a better prognosis for the patient.

PMID- 1979012
TI  - Nucleotide sequence of mouse HSP60 (chaperonin, GroEL homolog) cDNA.
AB  - The cDNA sequence of the 60 kDa heat-shock protein from mouse 3T3 cells has been
      determined. The deduced amino acid sequence of mouse hsp60 protein differs from
      the corresponding proteins from Chinese hamster and human cells in 7 and 13
      residues, respectively, most of which are conservative replacements.

PMID- 1979013
TI  - Receptor expression and oxidase activity in human neutrophils: regulation by
      granulocyte-macrophage colony-stimulating factor and dependence upon protein
      biosynthesis.
AB  - Incubation of human bloodstream neutrophils with 50 u/ml recombinant granulocyte
      macrophage colony-stimulating factor (rGM-CSF) "primed" the respiratory burst (as
      assessed by fMet-Leu-Phe stimulated luminol-dependent chemiluminescence) and
      resulted in a rapid (within 15 min) up-regulation of expression of CD11b and CD18
      (as measured by FACS analysis). This rapid "priming" and modulation of receptor
      expression was not inhibited by cycloheximide and hence appeared to be
      independent of de novo protein biosynthesis. When neutrophils were incubated for
      up to 5 h in culture, the fluorescence distributions of CD11b and CD18 declined
      indicating the loss of expression of these receptors as the neutrophils aged, but
      in rGM-CSF treated suspensions receptor expression was maintained. When
      neutrophils were incubated in the presence of cycloheximide, they progressively
      lost their ability to generate reactive oxidants in response to fMet-Leu-Phe so
      that by 5 h incubation with this inhibitor they could only generate about 25% of
      the oxidative response stimulated in untreated cells, and the expression of CD16
      and CD18 was grossly impaired. Similar effects were observed in rGM-CSF treated
      suspensions except that cycloheximide required longer incubation times (typically
      4-5 h) before impairment of function or receptor expression occurred. These data
      show that de novo protein biosynthesis is required for both the maintenance of
      neutrophil function and also for the continued expression of some plasma membrane
      receptors.

PMID- 1979014
TI  - [Expression of P-glycoprotein 170 (GP 170) and drug resistance in human cancers].
AB  - In vitro models with multiple drug resistance (MDR) phenotype have been
      frequently related to hyperproduction of the 170 kd membrane glycoprotein, the so
      called 170 GP. This protein is a pump able to extrude from cytoplasm drugs with
      various structures and mechanisms such as doxorubicin (DXR) or vinblastin (VLB).
      The MDR1 gene encodes the GP 170. MDR1 gene expression is low in most of the
      normal tissues, but high in some tissues such as colon, kidney, or liver. In
      these tissues, the GP 170 would ensure a detoxifying function related to cellular
      toxic compounds. There is a broad range of MDR1 gene expression in human tumors
      as a result of several factors. Of particular importance are the tissue origin
      from which the cancer derives and previous chemotherapy. In some cancers which
      often exhibit acquired chemoresistance, such as non Hodgkin's lymphomas,
      leukemias, sarcomas or neuroblastomas, an increase of MDR1 gene expression
      following previous chemotherapy has been frequently observed. Moreover in these
      cancers, a relationship between MDR1 transcript levels and clinical response to
      chemotherapy could exist as shown in several studies including one of ours.
      Hematosarcoma in the adult and some pediatric cancers seem to be models in which
      MDR1 gene expression may have a clinical relevance. Thus, an increase of MDR1
      gene expression during the course of chemotherapy would lead the clinician to
      choose "non MDR related" agents such as DXR, VLB; or to use agents that are able
      to reverse MDR phenotype.

PMID- 1979016
TI  - Early HIV infection.

PMID- 1979015
TI  - Five year prospective study of HIV infection in the Edinburgh haemophiliac
      cohort.
AB  - OBJECTIVE: To identify measures of immune state that reflect the course of HIV
      related disease in order to predict deterioration of symptoms and assess response
      to treatment. DESIGN: Five year longitudinal clinical and laboratory study.
      SETTING: Regional haemophilia centre, university virology laboratory, and Medical
      Research Council laboratory. PATIENTS: 32 Patients with haemophilia A exposed to
      a single batch of HIV contaminated factor VIII concentrate from the Scottish
      National Blood Transfusion Service in 1984 who were followed up regularly in
      Edinburgh (31) or abroad (one). MAIN OUTCOME MEASURES: Counts of circulating T
      cell subsets (CD4 and CD8); plasma beta 2 microglobulin, neopterin, and IgA
      concentrations; and delayed type hypersensitivity to multiple skin test antigens.
      RESULTS: 18 Patients who seroconverted after exposure had received significantly
      more contaminated factor VIII than the 14 who did not (mean 43 (range 9-109) v 15
      (3-30) phials, p less than 0.01). The two groups were not distinguishable by
      other criteria before exposure. The group that seroconverted subsequently showed
      a progressive fall in mean circulating CD4 lymphocytes and an increase in plasma
      beta 2 microglobulin and neopterin concentrations. From 1987 patients in this
      group also showed an increase in mean circulating CD8 lymphocytes and in plasma
      IgA concentration, neither of which was seen in patients who did not seroconvert.
      Patients with HIV antibody who developed Centers for Disease Control category IV
      symptoms within five years after infection showed more extreme changes in all
      measures, except CD8 lymphocyte count, than those whose symptoms remained in
      categories II and III. Skin test reactivity declined to barely detectable levels
      in all patients positive for HIV antibody. CONCLUSIONS: Serial estimates of
      circulating CD4 lymphocytes and of plasma beta 2 microglobulin concentration are
      the most reliable measures of disease progression; of these, beta 2 microglobulin
      concentration seems to be the better predictor of impending serious symptoms.
      High IgA concentrations reflect rather than predict disease state. Individual
      variation in most measures is such that a wide range of measurements should be
      used in assessing the effects of trial treatment in HIV infected patients without
      symptoms.

PMID- 1979018
TI  - Diet, nutrition and dental caries. Proceedings of the 2nd European Congress. July
      9-11, 1989, York, UK.

PMID- 1979017
TI  - Iatrogenic torsion of an undescended testis.

PMID- 1979019
TI  - Antigen processing and presentation by epidermal Langerhans cells. Induction of
      immunity or unresponsiveness.
AB  - The seminal observation made 30 years ago that T cells do not discriminate
      between native and denatured proteins, whereas B cells generally do, can now be
      explained by the fact that T cells never see antigens in their native
      conformation and that intact proteins cannot associate simultaneously with MHC
      molecules and the TCR. This difference in the ability to recognize antigen based
      on conformational specificity appears to be a consequence of the fact that the T
      cell sees antigen not free in solution, but on the surface of an APC in
      association with MHC molecules. The metabolic events that protein antigens
      undergo within APC, prior to their presentation in an appropriately processed
      form to T cells, are called antigen processing. The end-product of antigen
      processing for CD4+ T cells is a relatively short peptide fragment bound to class
      II MHC molecules on the surface of an APC that can be recognized by the TCR on
      the T cells. Because this event is difficult to monitor directly, antigen
      processing can only be assayed in conjunction with the temporally distal event of
      T-cell activation, manifested ultimately as proliferative responses or lymphokine
      secretion. In addition to occupancy of the TCR by the peptide/class II complex,
      several other antigen-nonspecific receptor-ligand interactions between APC and T
      cells are required for optimal T-cell activation. M phi, B cells, and LC/DC
      comprise the principal APC for CD4+ T cells. M phi and B cells have been studied
      extensively with respect to their antigen processing and presenting capacities.
      Only recently, however, have such capacities been investigated in LC and DC;
      these studies now indicate freshly isolated LC (but not cultured LC and DC) to
      possess efficient antigen processing capabilities. In this respect, LC have been
      proposed to represent evolving (or "maturing") forms of DC: Freshly isolated LC
      (which retain morphologic and functional properties of epidermal LC in situ) are
      the equivalent of tissue forms of DC, whereas cultured LC resemble lymphoid or
      circulating DC. Cultured LC and DC appear to be the sole effective APC for
      inducing primary T-cell responses in vitro. Possibly underlying this property is
      the ability of cultured LC and DC (but not M phi, B cells, or freshly isolated
      LC) to induce formation of T-cell clusters during the course of such responses.
      The capacity of accessory cells to function as APC varies depending upon the type
      of APC and T cells examined.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1979020
TI  - Vasculitis.
AB  - Vasculitis may be defined as damage to blood vessels induced by pathologic
      processes, resulting in compromise of function of the organ in which the blood
      vessels reside. A large number of syndromes and disease processes exist in which
      vasculitis plays a key role. Selected vasculitic syndromes of special interest to
      dermatologists are discussed in this article.

PMID- 1979021
TI  - Acquired immunodeficiency syndrome.
AB  - The occurrence of unusual infections, in particular Pneumocystis carinii
      pneumonia and the rare neoplasm Kaposi's sarcoma, in previously healthy
      homosexual men in the late 1970s heralded the epidemic of human immunodeficiency
      virus infection, the most severe form of which is the acquired immunodeficiency
      syndrome.

PMID- 1979022
TI  - Effects of acute and chronic ethanol administration and its withdrawal on the
      level and binding of somatostatin in rat brain.
AB  - 1. Acute ethanol administration resulted in an increase in the total number of
      specific somatostatin receptors in rat frontoparietal cortex and hippocampus, and
      a decrease in the level of somatostatin-like immunoreactivity in the hippocampus
      but not in the frontoparietal cortex. 2. Chronic administration of ethanol caused
      a decrease in the number of somatostatin receptors in the frontoparietal cortex
      but not in the hippocampus, although the level of somatostatin-like
      immunoreactivity was unchanged in both brain areas. 3. A week after suppressing
      ethanol the value for specific binding of tracer to somatostatin receptors in the
      frontoparietal cortex was not significantly different from that of the control
      rats, although the actual number of receptors was slightly lower. 4. These
      results suggest a possible role for somatostatin in the nervous system during
      alcoholism and the post-withdrawal reaction.

PMID- 1979023
TI  - Models and computers in diabetes research and diabetes care. XIIIth International
      Karlsburg Symposium on Problems of Diabetes. Dresden, G.D.R., 16-18 October 1989.
      Proceedings.

PMID- 1979024
TI  - Localization of mouse melanoma growth stimulatory activity gene (Mgsa) between
      Afp and Gus on chromosome 5 using interspecific backcross mice.
AB  - Melanoma growth stimulatory activity (Mgsa) is a polypeptide mitogen and a
      possible autocrine growth factor for melanoma and other tumor cells. A
      restriction fragment length variant of Mgsa was followed in interspecific
      backcross mic Mgsa was localized between Afp and Gus on mouse chromoson 5, distal
      to known loci affecting skin pigmentation.

PMID- 1979025
TI  - Genetic linkage group (ARG1-D6S33-MYB) on chromosome 6q containing the arginase-1
      and MYB genes.

PMID- 1979026
TI  - Raised liver associated enzyme activity and post-prandial bile acid
      concentrations in sera from treated diabetic outpatients.
AB  - Aspartate aminotransferase, alanine aminotransferase and gamma-glutamyl
      transferase activities were measured in sera from 411 diabetic outpatients and
      were raised in 26 (6.4%), 34 (8.3%) and 62 (15.2%) patients, respectively. Serum
      total bile acid concentrations were raised in 4 patients (1%). Percentage
      glycated hemoglobin A1, serum fructosamine concentration and plasma glucose
      concentration were also measured. No relationship between the presence of raised
      enzyme activity and mature age, short duration of diabetic treatment regimen or
      glycemic control was found. Twenty-six patients with an alanine aminotransferase
      activity greater than 60 U/l were reviewed at 23 +/- 6.5 weeks. The activity of
      this enzyme had fallen to within the reference interval in 15 (58%). In the other
      11 patients, its median activity was 75 U/l (range 51-181 U/l). Median gamma
      glutamyl transferase activity had risen in these 11 patients from 78 U/l to 93
      U/l (P less than 0.01). No statistical differences in treatment regimen or
      glycemic control were found between these two groups. Raised liver-associated
      enzyme activity in treated stabilised diabetic outpatients should therefore not
      be attributed to poor glycemic control or diabetic treatment regimen.

PMID- 1979027
TI  - [Drug-induced absence status: the significance of EEG in diagnosis and
      treatment].
AB  - Four patients with an absence status induced by drugs, are described. In three
      patients the use of neuroleptics was the probable cause, in the other
      indomethacin could be incriminated. As yet an absence status after treatment with
      these medicaments has not been described. Clinically, the diagnosis was not
      unequivocal. The EEG gave clear results, rapidly indicating the cause of the
      patient's clinical condition.

PMID- 1979028
TI  - Glucocorticoid inhibition of growth in rats: partial reversal with somatostatin
      antibodies.
AB  - Clinically, glucocorticoids are important immunosuppressive hormones. Yet, these
      steroids are also potent inhibitors of growth. We hypothesized that
      glucocorticoids may partially inhibit growth by increased somatostatin (SRIF)
      secretion. We tested this hypothesis using passive immunization techniques. Male
      rats (approximately 50 g) were treated daily (ip) for 33 days with saline (SAL)
      or dexamethasone (DEX, 40 micrograms/kg) and every fourth day with normal sheep
      serum (NSS) or SRIF antiserum (SRIF-ab, 0.25 ml). Body wts were recorded daily.
      Groups (n = 6) were: 1) SAL + NSS, 2) SAL + SRIF-ab, 3) DEX + NSS, and 4) DEX +
      SRIF-ab. Regression analysis of the growth curves clearly demonstrated
      differences in body wt gain for the four treatment groups (P less than 0.01).
      Final body wt of SAL + NSS treated rats was 285 +/- 5 g and 285 +/- 12 g in SAL +
      SRIF-ab treated rats. DEX + NSS treated rats weighed significantly less (227 +/-
      4 g, P less than 0.01) than SAL-treated rats. This glucocorticoid-induced
      decrease in body wt was partially reversed by the concomitant treatment of rats
      with SRIF-ab (241 +/- 6 g, P less than 0.05). This observation leads to the
      conclusion that the inhibitory effect of glucocorticoids on growth may be
      mediated, in part, by increased SRIF secretion.

PMID- 1979029
TI  - Rapid inactivation and phosphorylation of pyroglutamyl peptidase II in Y-79 human
      retinoblastoma cells after exposure to phorbol ester.
AB  - Pyroglutamyl peptidase II (EC 3.4.19.-), a membrane-bound metalloproteinase, is a
      highly specific TRH-degrading enzyme. Exposure of Y-79 human retinoblastoma cells
      to 12-0-tetradecanoyl phorbol 13-acetate (TPA) decreased the activity of this
      enzyme in a time- and concentration-dependent manner (IC50 5 x 10(-9) M). After
      15 min of TPA treatment, only 10% of pyroglutamyl peptidase II activity remained.
      TPA treatment did not affect the activity of the cytosolic enzyme pyroglutamyl
      peptidase I (EC 3.4.19.3) or the membrane-bound enzyme dipeptidyl peptidase IV
      (EC 3.4.19.3). Pretreatment of the cells with the protein kinase C inhibitors H-7
      or sphingosine prevented the inactivation of pyroglutamyl peptidase II by TPA.
      The time course of the TPA-mediated effect paralleled the time course of
      translocation and activation of protein kinase C in this cell line. Immunoblot
      analysis demonstrated that inactivation of pyroglutamyl peptidase II was not due
      to dissociation or internalization of this enzyme molecule. Incubation of TPA
      activated Y-79 cell membranes with gamma-[32P]-ATP followed by
      immunoprecipitation revealed a time-dependent phosphorylation of a 48 kilodalton
      subunit of pyroglutamyl peptidase II. These studies indicate that the phorbol
      ester effect is mediated by protein kinase C, and reveal a mechanism of
      potentiation of the action of TRH at its target sites.

PMID- 1979030
TI  - Mechanisms of impaired growth hormone secretion in genetically obese Zucker rats:
      roles of growth hormone-releasing factor and somatostatin.
AB  - GH secretion is markedly blunted in obesity; however, the mechanism(s) mediating
      this response remains to be elucidated. In the present study we examined the
      involvement of the two hypothalamic GH-regulatory hormones, GH-releasing factor
      (GRF) and somatostatin (SRIF), using the genetically obese male Zucker rat.
      Spontaneous GH, insulin, and glucose secretory profiles obtained from free
      moving, chronically cannulated rats revealed a marked suppression in amplitude
      and duration of GH pulses in obese Zucker rats compared to their lean littermates
      (mean 6-h plasma GH level, 3.9 +/- 0.4 vs. 21.5 +/- 3.8 ng/ml; P less than
      0.001). Obese rats also exhibited significant hyperinsulinemia in the presence of
      normoglycemia. The plasma GH response to an iv bolus of 1 microgram rat GRF-(1
      29)NH2, administered during peak and trough periods of the GH rhythm, was
      significantly attenuated in obese rats at peak (137.4 +/- 26.1 vs. 266.9 +/- 40.7
      ng/ml; P less than 0.02), although not at trough, times. Passive immunization of
      obese rats with a specific antiserum to SRIF failed to restore the amplitude of
      GH pulses to normal values; the mean 6-h plasma GH level of obese rats given SRIF
      antiserum was not significantly different from that of obese rats administered
      normal sheep serum. Both pituitary wet weight and pituitary GH content and
      concentration were reduced in the obese group. Measurement of hypothalamic GRF
      immunoreactivity revealed a significant (P less than 0.05) reduction in the
      mediobasal hypothalamic GRF content in obese rats (503.2 +/- 60.1 pg/fragment)
      compared to that in lean controls (678.1 +/- 50.2 pg/fragment), although no
      significant difference was observed in hypothalamic SRIF concentration.
      Peripheral SRIF immunoreactive levels were significantly (P less than 0.01)
      elevated in both the pancreas and stomach of obese rats. These results
      demonstrate that the genetically obese Zucker rat exhibits 1) marked impairment
      in both spontaneous and GRF-induced GH release, which cannot be reversed by SRIF
      immunoneutralization, 2) significant reduction in pituitary GH concentration, 3)
      depressed hypothalamic GRF content, and 4) elevated gastric and pancreatic, but
      not hypothalamic, SRIF levels. The findings suggest that the defect in pituitary
      GH secretion observed in the genetically obese Zucker rat is due, at least
      partially, to insufficient stimulation by hypothalamic GRF, and that SRIF does
      not play a significant role.

PMID- 1979032
TI  - The interaction with DNA of wild-type and mutant fushi tarazu homeodomains.
AB  - The in vitro DNA binding properties of wild-type and mutant fushi tarazu
      homeodomains (ftz HD) have been analysed. The DNA binding properties of the ftz
      HD are very similar to those of the Antp HD. In interference experiments with
      mutant ftz HDs, close approaches between specific portions of the ftz HD peptide
      and specific regions of the binding site DNA were mapped. A methylation
      interference, G7 on the beta strand of BS2, is absent from the interference
      pattern with a mutant ftz HD [ftz (R43A) HD] in which the Arg43 at the second
      position of helix III (the recognition helix) is replaced by an Ala. This
      indicated that Arg43 of the ftz HD is in close proximity to the N7 of G7 of the
      beta strand of BS2 in the major groove. The methylation and ethylation
      interference patterns with the ftz (NTD) HD, in which the first six amino acids
      of the homeodomain were deleted, were extensively altered relative to the ftz HD
      patterns. Methylation of A11 and G12 of the alpha strand and ethylation of the
      phosphate of nucleotide A12 of the alpha strand no longer interfere with binding.
      This indicated that the first six amino acids of the homeodomain of ftz interact
      with A11 of the alpha strand in the minor groove, the phosphate of the nucleotide
      A13 on the alpha strand and G12 of the alpha strand in the adjacent major groove
      of BS2. In a binding study using a change of specificity mutation [ftz (Q50K)
      HD], in which the Gln50 at the ninth position of the third helix is exchanged for
      a Lys (as in the bicoid HD), and variant binding sites, we concluded that
      position 50 of the ftz HD and the ftz (Q50K) HD peptides interacts with base
      pairs at positions 6 and 7 of BS2. These three points of contact allowed us to
      propose a crude orientation of the ftz HD within the protein-DNA complex. We find
      that the ftz HD and the Antp HD peptides contact DNA in a similar way.

PMID- 1979033
TI  - Biochemical and functional evidence for the presence of dopamine D1 receptors in
      the bovine ciliary body.
AB  - The present paper reports both functional and biochemical evidence for the
      presence of dopamine D1 receptors in the bovine ciliary body. Dopamine (DA) and
      dopamine D1 agonists (such as SKF 38,393) but not D2 agonists (such as LY
      141,865) produced a concentration-related decrease in the tone induced by a
      maximally active concentration of carbachol (1 x 10(-4)-5 x 10(-4) M). The
      maximal relaxation obtained was 100% of the carbachol response using 10(-5) M
      dopamine or 5 x 10(-6) M SKF 38,393. SCH 23,390, a D1 antagonist, but not (-)
      sulpiride, antagonized the effect of DA and SKF 38,393. In accordance with the
      functional data, radioreceptor binding experiments revealed the existence of a
      high affinity saturable [3H]SCH 23,390 binding to membranes prepared from ciliary
      body (Bmax: 344 fmol mg protein-1; Kd: 0.87 nM). The binding was specifically
      displaced by SCH 23,390, dopamine and dopamine D1 agonists, but not by
      norepinephrine, D2 agonists, or antagonists such as LY 141,865 and sulpiride. No
      specific binding was found when using dopamine D2 ligands, such as tritiated
      spiroperidol.

PMID- 1979031
TI  - Regulatory elements of the bithorax complex that control expression along the
      anterior-posterior axis.
AB  - The Drosophila bithorax complex (BX-C) controls segmental development by
      selectively deploying three protein products, Ubx, abd-A and Abd-B, within
      specific segments along the body axis. Expression of these products within any
      one segment (or, more accurately, parasegment) is affected by mutations clustered
      in a particular region of the BX-C. The regulatory regions defined by this
      genetic analysis span 20-50 kb and there is one region for each segmental unit.
      Here we describe regulatory elements from several of these regions, identified by
      fusion to a Ubx-lacZ gene and analysis in germline transformants. A small DNA
      fragment from the abx region programs expression with an anterior boundary in the
      second thoracic segment (parasegment 5). This anterior limit is appropriate,
      since the abx region normally controls Ubx in parasegment 5. Other regulatory
      regions of the BX-C that control development of parasegments 6, 7 or 8 contain
      similar regulatory elements that program expression with anterior limits in
      parasegments 6, 7 or 8, respectively. These experiments define a class of BX-C
      regulatory elements that control expression along the anterior-posterior axis.
      The early appearance of the lacZ patterns in embryos suggests a role for these
      elements in the initial activation of expression from the BX-C.

PMID- 1979034
TI  - Quantitative autoradiography of beta-adrenergic receptors in rabbit eyes.
AB  - Beta-adrenergic receptors were localized and quantified with autoradiographic
      methods in frozen sections of eyes of albino rabbits using [125I]cyanopindolol
      and [3H]dihydroalprenolol. Quantification in albino rabbits revealed highest beta
      2-adrenoceptor densities in the ciliary body, the corneal epithelium and the
      corneal endothelium. Moreover, the iris showed significant amounts of specific
      binding, whereas the retina and sclera are nearly free of these receptors.

PMID- 1979035
TI  - Formation of synaptic graft-host connections by noradrenergic locus coeruleus
      neurons transplanted into the adult rat hippocampus.
AB  - Transplants of cell suspension obtained from the locus coeruleus region of 13- to
      14-day-old rat fetuses were implanted into the hippocampal formation of intact
      adult rats or rats from which the noradrenergic afferents to the hippocampus had
      been removed by bilateral 6-hydroxydopamine (6-OHDA) injections into the dorsal
      tegmental noradrenergic bundle. The growth noradrenergic axons into the host
      hippocampus from the implant was studied at 4-8 months after surgery by
      immunohistochemistry using antisera raised against tyrosine hydroxylase or
      noradrenaline. In the animals with an intact noradrenergic system the host
      noradrenergic afferents were removed by bilateral dorsal bundle lesions 2 weeks
      before sacrifice. Fine axon-like fibers (diameter about 0.3 micron) and thick
      dendrite-like fibers (diameter about 1.3 micron), labeled immunohistochemically,
      were abundant and spread far from the graft. By electron microscopy,
      immunolabeled axon-like fibers formed mostly symmetrical synaptic contacts with
      nonlabeled spines and shafts of dendrites in the host. Labeled dendrite-like
      fibers of presumed graft origin penetrated deep into the host neuropil and
      received abundant afferents from nonlabeled axon terminals. The extent of graft
      derived noradrenergic axons and the synapses established with the host
      hippocampal neurons were similar in the chronically denervated animals and in the
      animals where the intrinsic noradrenergic afferents had been left intact until 2
      weeks before sacrifice. The results show that implanted embryonic noradrenergic
      neurons are able to innervate the hippocampus in both the presence and the
      absence of an intact intrinsic noradrenergic innervation and that the ingrowing
      axons form abundant synaptic connections with the host hippocampal neurons under
      both conditions. Dendritic processes from the grafted noradrenergic neurons that
      extend deep into the host tissue may receive a reciprocal synaptic host afferent
      input.

PMID- 1979036
TI  - [The effect of stimulation of the beta-adrenoreceptors on ion and water transport
      in the distal kidney tubule of the triton].
AB  - The ion and fluid reabsorption during perfusion of inter-tubular capillaries with
      different subtypes of beta-adrenergic agonists was studied in the newt distal
      tubule using the micropuncture technique and X-ray microanalysis. Isoproterenol
      (10(-5) M) did not affect the ion and water transport. Stimulation of beta 1
      adrenergic receptor with isoproterenol and beta 2-adrenergic antagonist ICI
      118.551 inhibited the fractional reabsorption of sodium, chloride and magnesium,
      the fluid reabsorption being changed insignificantly. Stimulation of beta 2
      adrenergic receptor with ventolin increased the fractional calcium reabsorption.
      The transport of water and other ions did not change.

PMID- 1979037
TI  - Molecular evolution of the Escherichia coli chromosome. III. Clonal frames.
AB  - PCR fragments, 1500-bp, from 15 previously sequenced regions in the Escherichia
      coli chromosome have been compared by restriction analysis in a large set of wild
      (ECOR) strains. Prior published observations of segmental clonality are
      confirmed: each of several sequence types is shared by a number of strains. The
      rate of recombinational replacement and the average size of the replacements are
      estimated in a set of closely related strains in which a clonal frame is dotted
      with occasional stretches of DNA belonging to other clones. A clonal hierarchy is
      described. Some new comparative sequencing data are presented.

PMID- 1979039
TI  - RFLP mapping in soybean: association between marker loci and variation in
      quantitative traits.
AB  - We have constructed a genetic map for soybean and identified associations between
      genetic markers and quantitative trait loci. One-hundred-fifty restriction
      fragment length polymorphisms (RFLPs) were used to identify genetic linkages in
      an F2 segregating population from an interspecific cross (Glycine max x Glycine
      soja). Twenty-six genetic linkage groups containing ca. 1200 recombination units
      are reported. Progeny-testing of F2-derived families allowed quantitative traits
      to be evaluated in replicated field trials. Genomic regions, which accounted for
      a portion of the genetic variation (R2 = 16 to 24%) in several reproductive and
      morphological traits, were linked to RFLP markers. Significant associations
      between RFLP markers and quantitative trait loci were detected for eight of nine
      traits evaluated. The ability to identify genes within a continuously varying
      trait has important consequences for plant breeding and for understanding
      evolutionary processes.

PMID- 1979038
TI  - Phylogenetically informative length polymorphism and sequence variability in
      mitochondrial DNA of Australian songbirds (Pomatostomus).
AB  - A combination of restriction analysis and direct sequencing via the polymerase
      chain reaction (PCR) was used to build trees relating mitochondrial DNAs (mtDNAs)
      from 50 individuals belonging to five species of Australian babblers
      (Pomatostomus). The trees served as a quantitative framework for analyzing the
      direction and tempo of evolution of an intraspecific length polymorphism from a
      third mitochondrial ancestor. The length polymorphism lies between the cytochrome
      b and 12S rRNA (srRNA) genes. Screening of mtDNAs within and between the five
      species with restriction enzymes showed that Pomatosomus temporalis was
      polymorphic for two smaller size classes (M and S) that are completely segregated
      geographically, whereas mtDNAs from the other four species were exclusively of a
      third, larger size (L). Inter- and intraspecific phylogenetic trees relating
      mtDNAs based on restriction maps, cytochrome b sequences obtained via PCR, and
      the two data sets combined were compared to one another statistically and were
      broadly similar except for the phylogenetic position of Pomatosomus halli. Both
      sets of phylogenies imply that only two deletion events can account for the
      observed intraspecific distribution of the three length types. High levels of
      base-substitutional divergence were detected within and between northern and
      southern lineages of P. temporalis, which implies a low level of gene flow
      between northern and southern regions as well as a low rate of length mutation.
      These conclusions were confirmed by applying coalescent theory to the statistical
      framework provided by the phylogenetic analyses.

PMID- 1979040
TI  - Phosphorylation of the v-erbA protein is required for its function as an
      oncogene.
AB  - The v-erbA oncogene of avian erythroblastosis virus (AEV) encodes a ligand
      independent mutated version of the chicken c-erbA alpha-encoded thyroid hormone
      receptor. The v-erbA gene product, a 75-kD gag/v-erbA fusion protein, is
      phosphorylated on Ser-16/17 of its v-erbA-encoded domain, and phosphorylation at
      this site is increased in vivo after activation of either the PKA or PKC signal
      transduction pathways. To test the hypothesis that phosphorylation of Ser-16/17
      regulates gag/v-erbA protein function, mutant proteins in which Ser-16/17 had
      been changed to alanine or threonine residues were analyzed for their ability to
      inhibit erythroid differentiation of ts v-erbB or ts v-sea-transformed
      erythroblasts at nonpermissive temperature. Conversion of Ser-16/17 into alanine,
      although not affecting nuclear localization or DNA binding of the gag/erbA
      protein, prevented phosphorylation of the v-erbA-encoded domain of the protein
      both in unstimulated cells or after stimulation by PKA and PKC activators. The
      nonphosphorylatable AA-gag/v-erbA protein proved unable to inhibit temperature
      induced differentiation of ts v-erbB and ts v-sea-transformed erythroblasts and
      to block expression of the erythrocyte-specific genes band 3 and carbonic
      anhydrase II. Back mutation of these alanine residues to serine resulted in the
      recovery of both normal phosphorylation levels and wild-type biological activity.
      In contrast, substitution of Ser-16/17 for threonine, which preserved
      phosphorylation in unstimulated cells but not PKA- and PKC-enhanced
      phosphorylation, resulted in a partially active gag/v-erbA protein. These
      results, together with the fact that the protein kinase inhibitor H7 resulted in
      both a dose-dependent inhibition of gag/v-erbA protein phosphorylation and the
      induction of terminal differentiation of AEV-transformed erythroblasts show that
      phosphorylation of gag/v-erbA protein is required for full biological activity.
      These results support the hypothesis that phosphorylation of the gag/v-erbA
      protein is important for transcriptional repression of at least some of its
      target genes in erythroid cells.

PMID- 1979041
TI  - Stable, high-level expression of a carcinoembryonic antigen-encoding cDNA after
      transfection and amplification with the dominant and selectable asparagine
      synthetase marker.
AB  - The introduction and expression of cloned genes in a wide variety of animal cells
      requires the convenient use of dominant selectable markers. Very few of these
      markers can be amplified in copy number, a necessary feature if variable and high
      level expression of the gene of interest is required. We describe the successful
      dominant transfection and amplification of a vector containing the Escherichia
      coli asparagine synthetase (AS)-encoding gene, asnA, transfected into a variety
      of human and rodent cell lines. An unlinked co-transfected expression vector
      containing the CEA cDNA, encoding human carcinoembryonic antigen, can be co
      amplified with the asnA marker leading to extremely high levels of CEA synthesis.
      In addition, we show that the expression of both the asnA marker and the co
      transfected CEA construct are stable in normal and amplified transfectants after
      prolonged culture in the absence of selective pressure.

PMID- 1979042
TI  - Presence of Epstein-Barr virus DNA in nasal lymphomas of B and 'T' cell type.
AB  - We studied 12 tumours from 11 Chinese patients with primary nasal lymphoma for
      presence of Epstein-Barr Virus (EBV) DNA, using Southern-blot analysis. These
      results were correlated with immunophenotype and T-cell receptor (TcR) or
      immunoglobulin gene rearrangement patterns. EBV DNA was detected in all nine
      tumours with a 'T' phenotype, in both primary and secondary sites. When the
      structure of the viral genomic termini was studied using the EcoRI-Dhet probe, a
      single clonal episomal band was demonstrated in five tumour samples, with one
      other case showing a biclonal pattern. However, none of these cases showed clonal
      rearrangement of TcR beta chain gene, and TcR gamma rearrangement was found only
      in one. The lineage of these phenotypic 'T' lymphomas therefore require further
      studies for confirmation. Two out of three B-lymphomas were also EBV DNA+; clonal
      EBV DNA was found in one. Their B-lineage was confirmed by detection of clonal
      immunoglobulin gene rearrangements. The association of EBV with an increasing
      number of lymphomas of different types highlights the need for continued study
      into its role in oncogenesis.

PMID- 1979043
TI  - Hybrid form of hairy cell leukemia and chronic lymphocytic leukemia.
AB  - We report a case with mixed features of hairy cell leukemia (HCL) and chronic
      lymphocytic leukemia (CLL), which may represent a hybrid form of these two
      entities. Hairy projections were demonstrated on leukemic cells in the peripheral
      blood. Surface marker studies of blood and spleen specimens by flow cytometry and
      immunohistochemistry showed immunophenotype characteristic of HCL, namely,
      monoclonal IgG-kappa, positive reactions to CD 11c, CD 19, CD 20, Cd 22, and HLA
      DR, but negative reactions to CD 3, CD 5, CD 7 and CD 10. The only atypical
      finding was the absence of CD 25. Immunogenotyping showed rearrangement of heavy
      chain and kappa light chain genes. Leukemic cells were also positive for tartrate
      resistant acid phosphatase (TRAP). A pseudosinus pattern was demonstrated in the
      spleen. However, the leukemic cells in the spleen showed atypical cytologic
      features. Clinically, the patient had generalized lymphadenopathy, high leukocyte
      counts, Coombs' negative hemolysis, hypoimmunoglobulinemia and IgG-kappa
      monoclonal gammopathy, features more consistent with CLL than HCL. Although only
      CD 11c, CD 22, CD 25 and TRAP are characteristic for HLC and CD 5, characteristic
      for CLL, a panel of eight markers is recommended for the differential diagnosis
      of HCL, CLL and other low-grade B-cell neoplasms, which may share some common
      features, making a clear-cut diagnosis difficult.

PMID- 1979044
TI  - From noncompliance to collaboration in the treatment of schizophrenia.
AB  - Although effective treatment for schizophrenia is available, patients' compliance
      with treatment prescriptions is notoriously poor. The authors reframe compliance
      as a collaborative relationship in which both the patient and practitioner assume
      responsibility for producing a treatment regimen to which the patient can adhere.
      Barriers that prevent a partnership in treatment may be related primarily to
      treatment techniques, to characteristics of the patient and his family, to the
      patient-clinician relationship, or to the treatment delivery system. A
      comprehensive approach to addressing these sources of noncompliance includes
      specific skills that can be acquired by the patient, family members, and the
      practitioner.

PMID- 1979045
TI  - Sexual side effects of antipsychotic medication: evaluation and interventions.
AB  - Sexual side effects of antipsychotic medications, which include disturbances of
      erection and ejaculation, changes in libido, and priapism in men and decreased
      libido, orgasmic dysfunction, and menstrual irregularities in women, are
      estimated to occur in 30 to 60 percent of persons taking the drugs. The authors
      review side effects associated with specific drugs and present guidelines for
      assessing whether sexual dysfunction is related to medication. Pharmacological
      interventions that may reduce antipsychotic-induced sexual dysfunction include
      gradually reducing the dose or changing the type of medication and administering
      other medications such as bethanechol, neostigmine, cyproheptadine, and
      bromocriptine that are known to improve sexual dysfunction.

PMID- 1979046
TI  - Linkage analysis of two cloned DNA sequences, DXS197 and DXS207, in
      hypophosphatemic rickets families.
AB  - The human X-linked hypophosphatemic rickets gene locus (HYP, formerly HPDR) has
      been previously localized by linkage analysis to Xp22.31-Xp21.3 and the locus
      order Xpter-DXS43-HYP-DXS41-Xcen established. Recombination between HYP and these
      flanking markers is frequently observed and additional markers have been sought.
      The polymorphic loci DXS197 and DXS207 have been localized to Xpter-Xp11 and Xp22
      Xp21, respectively. We have further localized DXS197 to Xpter-Xp21.3 by using a
      panel of rodent-human hybrid cells and have established the map positions of
      DXS197 and DXS207 in relation to HYP by linkage studies of hypophosphatemic
      rickets families. Linkage between DXS197 and the loci DXS43, DXS85, and DXS207
      was established with peak lod score values of 6.19, 0 = 0.032; 4.14, 0 = 0.000;
      and 3.01, 0 = 0.000, respectively. Multilocus linkage analysis mapped the DXS197
      and DXS207 loci distal to HYP and demonstrated the locus order Xpter-DXS85
      (DXS207, DXS43, DXS197)-HYP-DXS41-Xcen. These additional genetic markers DXS197
      and DXS207 will be useful as alternative markers in the genetic counseling of
      some families.

PMID- 1979047
TI  - Genetic heterogeneity in tuberous sclerosis.
AB  - Tuberous sclerosis (TSC) is an autosomal dominant disorder characterized by
      widespread hamartosis. Preliminary evidence of linkage between the TSC locus and
      markers on chromosome 9q34 was established, but subsequently disputed. More
      recently, a putative TSC locus on chromosome 11 has been suggested and genetic
      heterogeneity seems likely. Here we describe an approach combining multipoint
      linkage analysis and heterogeneity tests that has enabled us to obtain
      significant evidence for locus heterogeneity after studying a relatively small
      number of families. Our results support a model with two different loci
      independently causing the disease. One locus (TSC1) maps in the vicinity of the
      Abelson oncogene at 9q34 and a second locus (TSC2) maps in the region of the
      anonymous DNA marker Lam L7 and the dopamine D2 receptor gene at 11q23.

PMID- 1979048
TI  - Partial deletions of a sequence family ("DXS278") and its physical linkage to
      steroid sulfatase as detected by pulsed-field gel electrophoresis.
AB  - pCRI-S232 (DXS278) is a 7-kb genomic sequence that hybridizes to multiple
      polymorphic X-linked restriction fragments on standard Southern analysis.
      Physical mapping of pCRI-S232 by pulsed-field gel electrophoresis (PFGE) suggests
      that a sequence in S232 is repeated in multiple X-chromosomal regions in normal
      individuals. Steroid sulfatase (STS) and DXS237 each hybridize to two of six X
      linked SfiI fragments detected by S232. Two independent familial STS deletions,
      one of which is associated with a phenotype of ichthyosis plus ocular albinism
      (XI/OA1) and the other with nystagmus plus Rud syndrome, lack some but not all of
      the normal S232 PFGE fragments. We isolated a DNA fragment, E25B1.8, from a
      cosmid that contains S232. E25B1.8 detects a subset of the S232 polymorphic
      fragments on standard Southern blots plus new constant fragments; some, but not
      all, of the E25B1.8-hybridizing fragments are deleted in the XI/OA1 and Rud
      syndrome/nystagmus males. The simpler, but highly informative, polymorphism
      detected by E25B1.8 (DXS452) also eliminates an "intralocus" recombination seen
      with S232. We conclude that (1) males with STS deletions and complex phenotypes
      are partially deleted for DXS278, (2) DXS237 and part of DXS278 lie within 800 kb
      of STS, and (3) a repeat sequence within or around pCRI-S232 is probably located
      in multiple X-chromosomal locations spanning at least 2-3 Mb.

PMID- 1979049
TI  - DNA sequence polymorphisms in Alu repeats.
AB  - We have developed an efficient method for detection of sequence differences in
      genomic DNA based on a new principle (M. Orita et al., 1989, Genomics 5: 874
      879). Using this method, we show here that approximately half the Alu repeats
      interspersed in the human genome are significantly polymorphic. Analysis of Alu
      repeat polymorphism should be useful in construction of a high-resolution map and
      also in identifying genotypes of individuals for clinical and other purposes
      because the repeats are ubiquitous and the technique for their detection is
      simple.

PMID- 1979050
TI  - Deletion mapping of the medulloblastoma locus on chromosome 17p.
AB  - Isochromosome 17q has previously been observed consistently in cytogenetic
      studies of medulloblastoma, the most common posterior fossa neoplasm in children.
      We performed a restriction fragment length polymorphism (RFLP) investigation of
      medulloblastoma which showed a loss of chromosome 17p sequences in 45% of these
      tumors. This finding was predictive of a poor clinical response to treatment. A
      contiguous panel of markers permitted mapping of the deletion to 17p12-p13.1, the
      same chromosomal region for which loss of alleles has been shown in tumor
      specimens from patients with colon cancer, and the same region to which the p53
      gene has been mapped. This suggests that medulloblastoma is associated with a
      recessive oncogene on chromosome 17p that may be involved in the genesis of
      several embryologically unrelated neoplasms and that the absence of this gene in
      tumor tissue has prognostic significance.

PMID- 1979051
TI  - Multipoint linkage analysis and heterogeneity testing in 20 X-linked retinitis
      pigmentosa families.
AB  - Using multipoint linkage analysis in 20 families segregating for X-linked
      retinitis pigmentosa (XLRP), the lod scores on a map of eight RFLP loci were
      obtained. Our results indicate that under the hypothesis of homogeneity the
      maximal multipoint lod score supports one disease locus located slightly distal
      to OTC at Xp21.1. Heterogeneity testing for two XLRP loci suggested that a second
      XLRP locus may be located 8.5 cM proximal to DXS28 at Xp21.3. Further
      heterogeneity testing for three disease loci failed to detect a third XLRP locus
      proximal to DXS7 in any of our 20 XLRP families.

PMID- 1979052
TI  - Chromosomal distribution of three members of the human natriuretic peptide
      receptor/guanylyl cyclase gene family.
AB  - Chromosomal localization of the genes encoding three homologous human proteins,
      the ANPRA, ANPRB, and ANPRC cell surface receptors, was determined by polymerase
      chain reaction (PCR) analysis of genomic DNA from somatic cell hybrids. The ANPRA
      gene was assigned to 1q12----qter by intron-specific PCR. The ANPRB gene was
      assigned to 9p11----p22 using species-specific length variation in PCR fragments.
      The ANPRC gene was assigned to chromosome 5 using human-specific PCR primers
      identified by screening a human primer panel on parental DNA samples (shotgun
      primer screening). Chromosomal assignments based on PCR analysis were confirmed
      and the genes further sublocalized by in situ hybridization of cloned cDNA probes
      to human metaphase chromosomes. The ANPRA gene was sublocalized to 1q21----q22,
      the ANPRB gene to 9p12----p21, and the ANPRC gene to 5p13----p14.

PMID- 1979053
TI  - Linkage of the multiple endocrine neoplasia type 2B gene (MEN2B) to chromosome 10
      markers linked to MEN2A.
AB  - The syndrome of multiple endocrine neoplasia type 2B (MEN 2B) resembles that of
      MEN 2A in that both include medullary carcinoma of the thyroid, pheochromocytoma,
      and autosomal dominant inheritance, but is distinct in that MEN 2B patients have
      neuromas of the mucous membranes. MEN2A has been linked to RBP3, D10S5, FNRB,
      D10S15, and D10Z1 near the centromere of chromosome 10. We examined linkage
      between MEN2B and RFLPs on chromosome 10 in all available members in two or three
      generations of 14 kindreds. The centromere marker D10Z1 was linked to MEN2B with
      a peak lod score of 5.42 at theta = 0.02. One possible recombinant was observed
      between D10Z1 and MEN2B. Multipoint analysis of RFLPs at FNRB, D10Z1, RBP3, and
      D10S15 gave a peak lod score of 7.12 at the midpoint between D10Z1 and RBP3 on
      the long arm (band q11). The most likely gene order FNRB-D10Z1-MEN2B was 27 times
      more likely than MEN2B-FNRB-D10Z1 and 31/2 times more likely than FNRB-MEN2B
      D10Z1. Additional data will be required to establish the order of these loci with
      confidence.

PMID- 1979054
TI  - Genetic and physical mapping and population studies of a fibronectin receptor
      beta-subunit-like sequence on human chromosome 19.
AB  - A cDNA clone of the beta subunit of human fibronectin receptor (FNRB) detects two
      different polymorphic loci: (a) a codominant system previously mapped to the
      pericentromeric region of chromosome 10, the site of the functional FNRB gene;
      and (b) a dominant system not linked to the first one or to any chromosome 10
      marker tested. This second polymorphism is characterized by the presence or
      absence of a band (or a set of bands). We have used linkage analysis and biotin
      labeled in situ hybridization to map this dominant polymorphism to the short arm
      of chromosome 19; we hypothesize that it may be due to the insertion of part of
      the cDNA from the chromosome 10 gene into chromosome 19. This "insertion" is
      polymorphic in all populations studied.

PMID- 1979055
TI  - Optimizing restriction fragment fingerprinting methods for ordering large genomic
      libraries.
AB  - We present a statistical analysis of the problem of ordering large genomic cloned
      libraries through overlap detection based on restriction fingerprinting. Such
      ordering projects involve a large investment of effort involving many repetitious
      experiments. Our primary purpose here is to provide methods of maximizing the
      efficiency of such efforts. To this end, we adopt a statistical approach that
      uses the likelihood ratio as a statistic to detect overlap. The main advantages
      of this approach are that (1) it allows the relatively straightforward
      incorporation of the observed statistical properties of the data; (2) it permits
      the efficiency of a particular experimental method for detecting overlap to be
      quantitatively defined so that alternative experimental designs may be compared
      and optimized; and (3) it yields a direct estimate of the probability that any
      two library members overlap. This estimate is a critical tool for the accurate,
      automatic assembly of overlapping sets of fragments into islands called
      "contigs." These contigs must subsequently be connected by other methods to
      provide an ordered set of overlapping fragments covering the entire genome.

PMID- 1979056
TI  - Assignment of X-linked hydrocephalus to Xq28 by linkage analysis.
AB  - X-linked recessive hydrocephalus (HSAS) occurs at a frequency of approximately 1
      per 30,000 male births and consists of hydrocephalus, stenosis of the aqueduct of
      Sylvius, mental retardation, spastic paraparesis, and clasped thumbs. Prenatal
      diagnosis of affected males by ultrasonographic detection of hydrocephalus is
      unreliable because hydrocephalus may be absent antenatally. Furthermore, carrier
      detection in females is not possible because they are asymptomatic. Using four
      families segregating HSAS, we performed linkage analysis with a panel of X-linked
      probes that detect restriction fragment length polymorphisms. We report here that
      HSAS, in all tested families, is closely linked to marker loci mapping in Xq28
      (DXS52, lod = 6.52 at theta of 0.03; F8, lod = 4.32 at theta of 0.00; DXS15, lod
      = 3.40 at theta of 0.00). These data assign HSAS to the gene-dense chromosomal
      band Xq28 and allow for both prenatal diagnosis and carrier detection by linkage
      analysis.

PMID- 1979057
TI  - Chromosomal localization of the genes encoding two forms of the G protein beta
      polypeptide, beta 1 and beta 3, in man.
AB  - The signal-transducing G proteins are heterotrimers composed of three subunits,
      alpha, beta, and gamma. Multiple distinctive forms of the alpha, beta, and gamma
      subunits, each encoded by a distinct gene, have been described. To investigate
      further the structural diversity of the beta subunits, we recently cloned and
      characterized a novel cDNA encoding a third form of the G protein beta subunit,
      which we have termed beta 3. The protein corresponding to beta 3 has not yet been
      identified. The three forms of the beta subunit show 81-90% amino acid sequence
      identity. Previous studies had localized the human genes for the beta 1 and beta
      2 subunits to chromosomes 1 and 7, respectively. The present studies were
      designed to determine whether the gene encoding beta 3 is linked to either the
      beta 1 or the beta 2 gene. Genomic DNA was isolated from a panel of rodent-human
      hybrid cell lines and analyzed by hybridization to cDNAs for beta 1 and beta 3.
      Discordancy analysis allowed assignment of the beta 3 gene to chromosome 12 and
      confirmed the previous assignment of the beta 1 gene to chromosome 1. These
      results were confirmed and extended by using in situ chromosome hybridization,
      which permitted the regional localization of the beta 1 gene to 1pter----p31.2
      and the beta 3 gene to 12pter----p12.3. Digestion of human genomic DNA with 10
      restriction enzymes failed to disclose a restriction fragment length polymorphism
      for the beta 3 gene. These data indicate that there is considerable diversity in
      the genomic organization of the beta subunit family.

PMID- 1979058
TI  - Megabase scale restriction fragment length polymorphisms in the human major
      histocompatibility complex.
AB  - Pulsed-field gel electrophoresis of human peripheral blood lymphocyte DNA was
      used to ascertain the extent of megabase restriction fragment length variation in
      the HLA region of human chromosome 6 and to determine whether previously reported
      diversity was due to experimental variation or DNA polymorphism. Polymorphism was
      found to predominate in the vicinity of the class II DR, class III complement,
      and the class I A genes and to be limited or absent near the class II DP genes,
      the TNF genes, and the class I B and C genes. Thus, the MHC region is
      characterized by both fine and large-scale structural diversity.

PMID- 1979059
TI  - Linkage mapping of the highly informative DNA marker D21S156 to human chromosome
      21 using a polymorphic GT dinucleotide repeat.
AB  - A (GT)n repeat within the anonymous DNA sequence D21S156 was shown to be highly
      polymorphic in DNA from members of the 40 CEPH families. At least 12 alleles of
      this locus were recognized by electrophoresis on polyacrylamide gels of DNA
      amplified by the polymerase chain reaction (PCR) using primers flanking the (GT)n
      repeat. The polymorphism information content was 0.82. PCR amplification of DNA
      from somatic cell hybrid lines mapped D21S156 to human chromosome 21 and linkage
      analysis localized this marker close to the loci ETS2, D21S3, and HMG14 on
      chromosomal band 21q22.3. This polymorphism is highly informative and can serve
      as an anchor locus for human chromosome 21.

PMID- 1979060
TI  - Physical mapping by PFGE localizes the COL3A1 and COL5A2 genes to a 35-kb region
      on human chromosome 2.
AB  - The genes encoding the alpha 1 chain of Type III collagen (COL3A1) and the alpha
      2 chain of Type V (COL5A2) collagen have been mapped to the long arm of human
      chromosome 2. Linkage analysis in CEPH families indicated that these two genes
      are close to each other, with no recombination in 37 informative meioses. In the
      present study, DNA probes from the 3' ends of each gene have been physically
      mapped by pulsed-field gel electrophoresis. The probes recognized 11
      macrorestriction fragments in common, ranging from greater than 1000 kb MluI and
      NotI fragments to a 35-kb SfiI fragment. Therefore, the COL3A1 and COL5A2 genes
      appear to exist as a gene cluster on chromosome 2. This is the third example of a
      collagen gene cluster. Other examples include the COL4A1-COL4A2 genes on
      chromosome 13q and the COL6A1-COL6A2 genes on chromosome 21q. The physical
      proximity of these genes may indicate common evolution and/or regulation.

PMID- 1979061
TI  - CD4+ helper T cell depression in autism.
AB  - CD4+ (helper) T cells are a heterogenous population of lymphocytes including at
      least two distinct subpopulations. To investigate the possibility that immune
      abnormalities in some subjects with autism may involve abnormal distributions of
      CD4+ and/or CD8+ cells, (suppressor) T cells, peripheral blood lymphocytes of 25
      autistic subjects were characterized with monoclonal antibodies and flow
      cytometry. The autistic subjects had a significantly lower percentage and number
      of CD4+ cells, a lower number of T cells (CD2+ cells) and B cells (CD20+ cells),
      and a lower percentage and number of total lymphocytes than siblings and normal
      subjects. The level of blood values for female subjects appeared lower than those
      for males as compared to normal subjects of the same sex. These results suggest
      that a decrease in CD4+ cells is associated with autism.

PMID- 1979062
TI  - No recombinations between Tcra-V and Tcra-C gene segments in 669 backcross mice.
AB  - Because T-cell receptor (Tcr) genes may possibly function as non-major
      histocompatibility complex (MHC) immune response genes or predispose for
      autoimmune diseases, it is important to know how these genes are inherited. We
      found that Bgl I-digested DNA of BALB/c, C3H, DBA/2, and C57BL/6 exhibited
      restriction enzyme fragment length polymorphisms (RFLPs) for the Tcra-V1, Tcra
      V2, Tcra-V4, Tcra-V6, Tcra-V7, Tcra-V8, Tcra-V11, Tcra-V12, Tcra-V13, and Tcra-C
      gene segments. Inheritance of these RFLPs in 669 offspring from (BALB/c x
      C57BL/6) x BALB/c, (BALB/c x C57BL/6) x C57BL/6, (C57BL/6 x DBA2) x DBA/2, and
      (C57BL/6 x C3H) x C3H backcrosses was studied. Since we did not find any
      recombinations in the offspring, Tcra-V and Tcra-C gene segments are tightly
      linked and inherited as a haplotype. A peculiar finding was that 22 out of 103
      (BALB/c x C57BL/6) x BALB/c offspring, heterozygous for Tcra-C, had deleted a
      C57BL/6 Tcra-V1 band as well as Tcra-V2 and Tcra-V4 bands. As will be discussed,
      this deletion is probably caused by heterogeneity in the C57BL/6 breeding stock
      of a commercial supplier. In seven BXD and BXH recombinant inbred strains with
      known recombinations between the Tcra-C and Es-10 loci, all Tcra-V RFLPs
      cosegregated with the Tcra-C RFLP. This finding agrees with the conclusion from
      our backcross studies; namely that Tcra-V and Tcra-C gene segments are tightly
      linked.

PMID- 1979063
TI  - A distinct HLA-DRw8 haplotype characterizes patients with juvenile rheumatoid
      arthritis.
AB  - We studied the first domain of the HLA-DRB1, HLA-DQA1, and HLA-DQB1 loci of 67
      HLA-DRw8-positive Caucasians including 43 with early-onset pauciarticular
      juvenile rheumatoid arthritis (EOPA-JRA, alternatively known as early-onset
      pauciarticular juvenile chronic arthritis). Serology, restriction fragment length
      polymorphism (RFLP), and polymerase chain reaction (PCR) oligotyping revealed
      that 62, including all the EOPA-JRA patients, carried the HLA-DRB1*0801,
      DQA1*0401, DQB1*0402 genotype. Approximately one-fifth of the controls carried
      atypical HLA-DRB1, HLA-DQA1, and/or HLA-DQB1 loci on their HLA-DRw8 haplotype
      confirmed by family studies. DNA sequences of HLA-DRB1, DQA1, and DQB1 alleles in
      patients and controls were identical to those previously reported. Disease
      association studies in 113 EOPA-JRA patients and 207 controls unselected for HLA
      DRw8 revealed that the HLA-DRB1*0801, DQA1*0401, DQB1*0402 genotype was
      associated with a higher relative risk (RR) for disease (RR = 12.8, chi 2 = 48.8,
      P less than 10(-4)) than was the serologically defined presence of HLA-DRw8 (RR =
      8, chi 2 = 39, P less than 10(-4)). Further analysis suggested that the DQ genes
      on HLA-DRw8 haplotypes are as likely as the DR genes to contribute to the
      pathogenesis of EOPA-JRA. This study increases to five the number of HLA-DR/DQ
      haplotypes identified in HLA-DRw8 Caucasians.

PMID- 1979065
TI  - The mouse C-reactive protein gene maps to distal chromosome 1 and, like its human
      counterpart, is closely linked to the serum amyloid P component gene.

PMID- 1979064
TI  - Gene segments encoding membrane domains of the human immunoglobulin gamma 3 and
      alpha chains.
AB  - The carboxyterminal region of the heavy chains, according to its hydrophilic or
      hydrophobic properties, determines whether the immunoglobulin will be secreted or
      membrane-bound. We have determined the nucleotide sequences of the human IGHG3,
      IGHA1, and IGHA2 membrane exons isolated from genomic DNA libraries. The IGHG3 M1
      and M2 exons are separated by a long intron of 2.1 kilobases (kb) containing an
      highly repeated motif of 34 base pairs (bp). The IGHA1 and IGHA2 genes, like the
      mouse Igh-A gene, have a single exon encoding the extracellular, transmembrane,
      and cytoplasmic regions. For each class of immunoglobulins, the sequences of
      membrane exons are highly conserved between human and mouse, but no alignment is
      possible for the flanking regions. In contrast, for a same species, the sequences
      of the heavy chain membrane exons differ from one class to another. While the
      hydrophobic profile of the membrane core is well conserved, the cytoplasmic
      region differs in length and in composition. None of the intracellular domains
      presents the sequence implied in signal transduction, implying that membrane
      immunoglobulins need other proteins, which probably interact with the constant or
      membrane domain, to transmit signals leading to B-cell activation.

PMID- 1979067
TI  - Expression of intercellular adhesion molecule-1 (ICAM-1) on renal-cell cancer:
      possible significance in host immune responses.
AB  - In this study we examined the expression of intercellular adhesion molecule-1
      (ICAM-1) in 28 cases of renal-cell cancer (RCC). We also examined ICAM-1
      expression on RCC cell lines in response to cytokines. Immunohistochemistry
      revealed frequent expression (23 positive cases among the 28 RCCs) of ICAM-1 in
      RCC. The molecule was not detected on renal tubular cells as far as could be
      determined. Furthermore, the number of ICAM-1-positive cells in RCC was
      significantly correlated with the degree of mononuclear cell infiltration,
      involving mainly T lymphocytes and a smaller number of macrophages bearing the
      LFA-1 molecule. Expression of ICAM-1 on RCC cell lines was augmented by in vitro
      treatment with interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha and
      interleukin-1 (IL-1)beta. These results suggest that the expression of ICAM-1 on
      RCC might be modified by cytokines produced by tumor-infiltrating mononuclear
      cells, and that ICAM-1 expression on RCC might augment the host immune reaction.

PMID- 1979066
TI  - HLA-DP/DR interaction in children with juvenile rheumatoid arthritis.

PMID- 1979068
TI  - Participation of CD11a-c/CD18, CD2 and RGD-binding receptors in endogenous and
      interleukin-2-stimulated NK activity of CD3-negative large granular lymphocytes.
AB  - The effect of RGD-sequence-containing pentapeptides and monoclonal antibodies
      (MAbs) against the adhesion molecules CD11a-c/CD18, ICAM-1 (CD54) and CD2 on the
      binding and cytotoxicity of endogenous (freshly purified) and IL-2-stimulated CD3
      negative NK cells has been studied. Antibody to CD18 exerted the most significant
      inhibition of adhesion and cytotoxicity of endogenous NK cells to MOLT-4 lymphoma
      cells, followed by antibodies to CD2 and CD54. Antibodies to either CD11a, CD11b
      or CD11c did not inhibit adhesion when used separately, whereas as a mixture
      their inhibitory capacity was as strong as that of anti-CD18. Antibodies against
      CD18, CD54 and CD2 exerted an additive effect on the inhibition of adhesion.
      Their combination eradicated the binding of endogenous NK cells. The RGD
      containing peptide did not inhibit the binding or cytotoxicity of freshly
      purified NK cells to MOLT-4, whereas some inhibition was detected against the
      adenocarcinoma cell line COLO-205. According to FACS analysis, IL-2 increases the
      expression of CD2 and CD54 on NK cells. However, the relative contribution of the
      adhesion molecules to the NK cell binding did not change as a result of the
      stimulation with IL-2. The RGD-peptide substantially inhibited the binding of IL
      2-stimulated killer cells to COLO, and the combination of this peptide with MAbs
      to CD18, CD54 and CD2 practically blocked the adhesion. Our results indicate that
      both CD11a-c/CD18- (involving the 3 heterodimers) and CD2-dependent adhesion
      pathways are used by LGL in endogenous and IL-2 stimulated natural killing. In
      addition, RGD-binding receptors are involved in adhesion to some target cells.

PMID- 1979069
TI  - Expression and modulation by cytokines of the intercellular adhesion molecule-1
      (ICAM-1) in human central nervous system tumor cell cultures.
AB  - The intercellular adhesion molecule (ICAM-1) has been shown to be important in
      interactions involving cells of the immune system and to be upregulated in a
      number of cell culture systems by cytokines, including immune interferon (IFN
      gamma) and tumor necrosis factor-alpha (TNF-alpha). In the present study, we have
      determined by fluorescence-activated cell sorter (FACS) analysis and the anti
      ICAM-1 monoclonal antibody (MAb) CL203.4 the base-line expression of ICAM-1 and
      its modulation by recombinant IFN-beta, IFN-gamma and TNF-alpha in early passage
      (less than 15) human central nervous system (CNS) tumor-derived cell cultures.
      These cultures were established from various malignancies, including glioblastoma
      multiforme (GBM), astrocytoma (AST), ganglioglioma, medulloblastoma, meningioma
      and a pineal tumor. ICAM-1 expression was highest in the GBM- and AST-derived
      cell cultures and was lowest in the ganglioglioma and normal pineal cell
      cultures. Variable ICAM-1 expression was found, however, in tumors of the same
      histological group. In several cell cultures the variable expression observed by
      FACS was substantiated by the intensity of the molecular species
      immunoprecipitated by the anti-ICAM-1 MAb CL203.4 from these cells. All the cell
      cultures displayed variable but consistent increases in ICAM-1 expression
      following treatment with IFN-gamma or TNF-alpha. In general, the degree of
      increase in ICAM-1 expression was greatest in cultures exposed to TNF-alpha.
      Upregulation of ICAM-1 expression in an established glioblastoma multiforme cell
      line was of greater magnitude and more rapid following TNF-alpha treatment
      (within 2 to 3 hr) than exposure to IFN-gamma (by 24 hr). In several cultures,
      IFN-beta also increased ICAM-1 expression and enhanced the increase induced by
      TNF-alpha. The results of the present study indicate that variable expression of
      ICAM-1 is a common property of early passage cultures of CNS tumors and
      recombinant interferons and TNF-alpha can differentially upregulate ICAM-1
      expression in these CNS tumor cell cultures.

PMID- 1979070
TI  - TaqI RFLP of the TGF alpha gene in breast cancer.

PMID- 1979072
TI  - Implication of the HLA-DRB3 gene in Graves' disease: predominance of allele Dw24.
AB  - Using RFLP, the present study sets off to determine the MHC class II gene
      polymorphism in Graves' disease, in order to define the HLA-related genetic
      susceptibility. Considering the preferential link between Graves' disease and the
      HLA-DR3 antigen, 42 HLA-DR3 Graves' disease patients were studied and compared
      with 42 HLA-DR-matched controls. Hybridization with a DQ alpha probe of DNAs
      digested by Taq I revealed a polymorphism of the DR3 haplotype with an
      overrepresentation of a 2.1 kb(U) fragment in patients, but this was merely a
      sign of the linkage disequilibrium between U and B8DR3. Hybridization with the DR
      beta probe of DNAs digested by Taq I yielded more facts. It revealed the
      overrepresentation of the Dw24 specificity (Taq I:9.8 kb) in DR3 Graves' disease
      patients. This study thus enabled us to determine precisely the susceptibility
      linked to the DR3 haplotype, implicating the DRB3 gene and its Dw24 allele, which
      appear to be the most reliable markers of the disease, providing a higher
      relative risk than B8DR3.

PMID- 1979071
TI  - Properties of B cells and Thy-1-antigen-expressing cells infiltrating rat renal
      allografts.
AB  - We have examined (1) the frequency of B cells secreting antibodies against donor
      major histocompatibility complex (MHC) antigens and (2) the properties of Thy-1
      antigen-expressing leukocytes in rats rejecting renal allografts. Our results
      show that B cells secreting antibodies are present in the inflammatory cell
      population at the frequency of 1:850. Among them only 1 out of 2-150 is engaged
      in production of antibodies directed to the graft MHC antigens, depending on the
      method of assay. This suggests that despite the observed significant production
      of nonspecific immunoglobulin in situ, only a minority of the B-cell population
      is specifically committed to the graft MHC antigens. This finding is concordant
      with the described previously low frequencies of the T cells specifically
      directed toward the graft MHC antigen. The role of the "immunologically
      noncommitted" cells in graft rejection is unknown. We have found that a
      substantial part (up to 60%) of inflammatory cells invading a rat kidney
      allograft express the Thy-1 antigen. This suggests that they might be immature
      (progenitor?) cells and, therefore, unable to respond to the graft antigens.
      Progenitor-like properties of these cells have been confirmed by their ability to
      reconstitute lethally irradiated syngeneic rat. Finally, these immature cells are
      of lymphoid, not of myeloid, linkage, because they do not proliferate in the
      presence of GM-CSF.

PMID- 1979073
TI  - Frequency and associations of HLA class II TaqI allogenotypes in the Northern
      Ireland population.
AB  - HLA-DR allogenotyping was performed on a panel of 1019 Caucasian individuals from
      the Northern Ireland population, of whom 150 were also HLA-DQ allogenotyped,
      using a single enzyme (TaqI)/multiple probe system. TaqI/DR beta restriction
      fragment length polymorphisms correlate well with the serologically defined
      specificities and in addition detect further subtypes of these associated with DQ
      or Dw specificities. The most frequent DR beta allogenotypes were DR beta 15, DR
      beta 4, and DR beta 17 (Dw24). The frequency of the subtypes of DR beta 4
      associated with DQ beta 3 (TA10+) was higher than that reported elsewhere for
      Caucasian populations, whereas the frequency of the subtypes of DR4 beta
      associated with DQ beta 3(TA10-) was subsequently reduced. The subtypes of DR
      beta 4 associated with DQ beta 3 (TA10+) were strongly associated with B44. The
      TaqI/DX alpha gene polymorphisms, as revealed by the DQ alpha cDNA probe, were
      found to be associated with DR beta allogenotypes.

PMID- 1979075
TI  - Inactivation of bacterial glutamine synthetase by ADP-ribosylation.
AB  - Glutamine synthetase from Escherichia coli was inactivated by chemical
      modification with arginine-specific reagents (Colanduoni, J. A., and Villafranca,
      J. J. (1985) Biochem. Biophys. Res. Commun. 126, 412-418). E. coli glutamine
      synthetase was also a substrate for an erythrocyte NAD:arginine ADP
      ribosyltransferase. Transfer of one ADP-ribosyl group/subunit of glutamine
      synthetase caused loss of both biosynthetic and gamma-glutamyltransferase
      activity. The ADP-ribose moiety was enzymatically removed by an erythrocyte ADP
      ribosylarginine hydrolase, resulting in return of function. The site of ADP
      ribosylation was arginine 172, determined by isolation of the ADP-ribosylated
      tryptic peptide. Arginine 172 lies in a central loop that extends into the core
      formed by the 12 subunits of the native enzyme. The central loop is important in
      anchoring subunits together to yield the spatial orientation required for
      catalytic activity. ADP-ribosylation may thus inactivate glutamine synthetase by
      disrupting the normal subunit alignment. Enzyme-catalyzed ADP-ribosylation may
      provide a simple, specific technique to probe the role of arginine residues in
      the structure and function of proteins.

PMID- 1979074
TI  - Characterization of putative cytoskeletal proteins from a trypanosomatid and
      their comparative binding to microtubules and soluble tubulin.
AB  - The corset of microtubules which encloses the cell body of Crithidia fasiculata
      displays cross-links joining tubules to each other and to plasma membrane. Two
      proteins, designated COP-33 and COP-61 on the basis of their subunit Mr values,
      have been considered putative components of this apparatus because of their
      abundance in isolated cytoskeleton and their ability to cross-link brain
      microtubules in vitro. The oligomeric structures of the native proteins have now
      been characterized, and they have been shown to be basic, rather symmetrical, and
      to require detergent for solubilization. Using monospecific antibodies, enzyme
      linked immunoassays of subcellular fractions have shown that each is 5-fold
      enriched in the microtubule plasma membrane fraction and absent from flagellar
      and some internal membranes. The binding of each to soluble tubulin and to
      microtubules has been systematically studied and compared with that of two
      noncytoskeletal protein ligands (glycolytic enzymes). The observed positive
      cooperatively was unexpected for binding of these large ligands to microtubules.
      In each case the maximum number of mol of ligand bound per mol of tubulin (0.5
      1.0) was identical whether the latter was dissociated or assembled and so were
      the dissociation constants (1.3-6.0 x 10(-7) M) for three of the ligand proteins.

PMID- 1979076
TI  - Serum and extracellular calcium modulate induction of cytochrome P-450IA1 in
      human keratinocytes.
AB  - Culture conditions allowing for cytochrome P-450IA1 induction by 2,3,7,8
      tetrachlorodibenzofuran (TCDF) in normal human keratinocytes (HK) were
      investigated. HK grown in serum-free low extracellular Ca2+ (0.1 mM) medium did
      not accumulate P-450IA1 mRNA in response to TCDF. If, however, the cultures were
      pretreated for more than 24 h with either serum or elevated extracellular Ca2+
      (2.0 mM), induction of P-450IA1 was obtained by TCDF. Serum and elevated Ca2+
      concentrations were found to be additive in this respect. When analyzing HK
      derived from five individuals, no apparent difference was found in the relative
      induction of P-450IA1 by increasing concentrations of TCDF, giving an EC50 of
      approximately 2 nM. The permissive effect of serum and elevated Ca2+ could be
      conferred to a reporter gene by the -1140 to +2435 part of the human CYPIA1 gene.
      Culture conditions allowing for P-450IA1 induction correlated with conditions
      that induced mRNA corresponding to the differentiation specific enzyme epidermal
      transglutaminase. This finding, together with the known differentiation promoting
      effects of serum and elevated Ca2+, suggest that terminal differentiation is
      necessary for P-450IA1 induction in HK by Ah receptor ligands.

PMID- 1979077
TI  - Characterization of a fully active N-terminal 37-kDa polypeptide obtained by
      limited tryptic cleavage of pig kidney D-amino acid oxidase.
AB  - In order to obtain further information on the structure of D-amino acid oxidase
      (EC 1.4.3.3), limited proteolysis experiments have been carried out on its apo-,
      holo-, and holoenzyme-benzoate forms. The enzyme is unsensitive to 10% (w/w)
      chymotrypsin, while incubation with 10% (w/w) trypsin, under nondenaturating
      conditions, produces inactivation and proteolysis patterns which are different
      for the three forms of enzyme analyzed. These results confirm the previously
      reported conformational changes which occur upon binding of coenzyme to the
      apoprotein, and of benzoate to holoenzyme. The stable 37.0-kDa polypeptide,
      obtained from the apo- and holoenzyme-benzoate complex upon cleavage of a C
      terminal 2.0-kDa fragment, retains full catalytic activity with unaltered kinetic
      parameters, and the coenzyme binding properties of the native enzyme. These
      results are in agreement with the tentative localization of the FAD-binding
      domain in the N-terminal region of the enzyme, and with the hypothesis that the
      function of the C-terminal region of D-amino acid oxidase could be related to the
      import of the enzyme into the peroxisomes, as suggested by Gould et al. (Gould,
      S. J., Keller, G. A., and Subramani, S. (1988) J. Cell. Biol. 107, 897-905).

PMID- 1979078
TI  - Sixth International Congress of Mucosal Immunology, July 23, 1990. Dental caries
      vaccines.

PMID- 1979079
TI  - Improvement of "a BASIC program to construct evolutionary trees from restriction
      endonuclease data" with the use of PASCAL.

PMID- 1979080
TI  - Effects of rIFN alpha, beta, and gamma on the morphology, proliferation, and cell
      surface antigen expression of human dermal microvascular endothelial cells in
      vitro.
AB  - The influence of recombinant human interferon alpha 2a (rIFN alpha), recombinant
      human interferon beta 1 (rIFN beta), and recombinant human interferon gamma (rIFN
      gamma) on human dermal microvascular endothelial cells (HDMEC) cultured in vitro
      was studied in various rIFN concentrations (0.1 IU/ml-10(4) IU/ml) over 2, 3, 4,
      6, 8, and 10 d. Cell morphology and ultrastructure, cell proliferation,
      expression of class II alloantigens (HLA-DR and HLA-DQ), and intercellular
      adhesion molecule-1 (ICAM-1) were investigated using an in vitro technique
      established in our laboratory. All rIFN tested induced alterations of typical
      HDMEC morphology; the cells became spindle-shaped and fibroblastoid, although
      they maintained their endothelial cell marker expression. Also, all IFN dose- and
      time-dependently inhibited the proliferation of HDMEC in vitro (rIFN alpha
      greater than beta greater than gamma), whereby rIFN alpha exerted the strongest
      growth-inhibitory effect. Alkaline phosphatase anti-alkaline phosphatase (APAAP)
      immunocytochemistry of the cultured cells showed dose- and time-dependent
      stimulation of ICAM-1 and class II antigen expression only by rIFN gamma (HLA-DR
      greater than HLA-DQ), rIFN alpha and beta did not exert any immunomodulatory
      activity on HDMEC in vitro. These results indicate that HDMEC are an important
      target for the action of IFN. Besides growth inhibition, it seems that rIFN gamma
      in particular may be involved in the modulation of leucocyte adhesion and
      trafficking by altering the immunophenotype of the endothelial cell population.

PMID- 1979081
TI  - Workshop on linkage analysis of hereditary skin diseases. University of
      California, San Francisco, April 22-24, 1990.

PMID- 1979082
TI  - Overview of the International Conference on Particle Detection, Metrology, and
      Control.
AB  - The 1990 International Conference on Particle Detection, Metrology, and Control
      (February, 1990) jointly sponsored by the Parenteral Drug Association, Inc. and
      The Institute for Environmental Sciences provided a point in time to measure the
      progress achieved in the solution of the particle measurement problems that were
      defined at the 1987 Particle Conference. This Conference was of special
      significance since it addressed the scientific problems whose solution is
      required for successful harmonization of world particulate measurements and
      standards. A summary of the major papers presented follows.

PMID- 1979083
TI  - Immunomodulation by LongoVital in patients with recurrent aphthous ulceration.
AB  - LongoVital (LV) (DK. Reg. No. 5178/75) is a herbal based tablet enriched with
      recommended doses of vitamins. Peripheral lymphocyte subsets: T-helper/CD4
      (OKT4+) and T-suppressor/cytotoxic/CD8 (OKT8+) were studied quantitatively in 31
      otherwise healthy patients with minor recurrent aphthous ulceration (RAU) during
      6 months' daily LV intake in a double-blind, randomized, crossover 1-year study.
      Fourteen had had LV during the first 6 months (GrA) and 17 LV during the latter 6
      months (GrB). OKT4+ percentages increased significantly during the LV period in
      both groups (P less than 0.05). OKT8+ percentages increased in both groups,
      however, only significantly in GrA (P less than 0.05). It is concluded that LV
      acts as an immunostimulator in patients with RAU and that the increase in T
      lymphocyte subsets may account for the previously reported benefit of LV in RAU
      prevention.

PMID- 1979084
TI  - Basic research yielding new detection and treatment targets.

PMID- 1979085
TI  - Field immobilization of bighorn sheep with xylazine hydrochloride and antagonism
      with idazoxan.
AB  - Xylazine hydrochloride was used to immobilize 124 Rocky Mountain bighorn sheep
      (Ovis canadensis canadensis) between 1983 and 1988. Doses of xylazine for free
      ranging lambs ranged from 70 to 130 mg with amounts increasing with lamb age.
      Average doses for 11 free-ranging adult males and 21 adult females darted from
      the ground were (means +/- SE) 363 +/- 16 and 251 +/- 7 mg, respectively. Adult
      females captured in "Stevenson's " box traps (n = 7) could be immobilized with
      significantly (P less than 0.001) less xylazine (93 +/- 9 mg) than free-ranging
      females but had similar induction times. Long recovery times associated with
      xylazine immobilization were eliminated with the intravenous administration of
      idazoxan (RX 781094) at an approximate dosage of 0.1 mg/kg. Eighteen sheep given
      idazoxan appeared fully recovered within 3 min of injection (means +/- SE = 1.2
      +/- 0.2 min). Four mortalities (three lambs, one yearling male) (3% of total)
      occurred before idazoxan was available for trial.

PMID- 1979086
TI  - [Clinical analysis of ascitic fluid in patients with liver cirrhosis and
      hepatocellular carcinoma].
AB  - To investigate the clinical significance of ascitic fluid in patients with a
      malignancy, an abdominal paracentesis to evaluate the ascitic fluid was performed
      in 10 patients with a hepatocellular carcinoma (HCC) and in 7 patients with liver
      cirrhosis (LC). The AFP levels in the ascitic fluid and in the serum of the HCC
      patients was found be significantly higher than that of the LC patients. In
      addition, the ratio of albumin/total protein in ascitic fluid was also higher in
      the HCC patients. However, no significant findings were uncovered with regard to
      the concentration of lipid in ascitic fluid, in either type of patient although 2
      HCC patients were found to have a very high concentration of total cholesterol.
      The cytological findings provided no reliable marker because of significant
      number of false negatives in the HCC patients. Also, there was no significant
      difference between the fibronectin levels in the ascitic fluid of either type of
      patients. This finding differs from previous studies, and suggests that the
      fibronectin levels in the ascitic fluid may not be a useful marker in determining
      a malignancy.

PMID- 1979088
TI  - Multiple endocrine neoplasia type IIb: a clinicopathological report.
AB  - The clinicopathological findings in a 12-year-old boy with multiple endocrine
      neoplasia type IIb (MEN-IIb) are presented. He demonstrated the characteristics
      of a Marfanoid habitus and had mucosal neuromas of the lips, tongue, eyelids, and
      cornea. The enlarged right thyroid lobe showed an increased thallium-201 chloride
      uptake, and the serum calcitonin level was markedly raised. A total thyroidectomy
      was performed. Histopathological examination showed an infiltrating medullary
      carcinoma of the thyroid (MCT) and metastatic spread to supraclavicular lymph
      nodes. Special stains, immunocytochemistry, and electron microscopy revealed
      mucin-containing follicular structures lined by calcitonin-positive and
      thyroglobulin-negative tumour cells. Ultrastructurally the mucosal neuromas
      consisted of proliferating perineurial and Schwann cells. The serum calcitonin
      level fell below 300 pmol/L, and his stools returned to normal postoperatively.
      Because the incidence of MCT in MEN-IIb is virtually 100%, a total thyroidectomy
      in high risk patients--even before clinical evidence of malignant tumours--may be
      the only hope of cure.

PMID- 1979087
TI  - [Effect of teprenone and H2-receptor antagonists on phosphatidylcholine synthesis
      in the isolated guinea pig gastric glands].
AB  - To better understand the mechanism of phosphatidylcholine synthesis in the
      stomach, [3H] choline incorporation into phosphatidylcholine in response to the
      drugs which have been commonly used for treating the patients with gastric ulcer
      was examined using isolated guinea pig gastric glands. Teprenone stimulated [3H]
      choline incorporation into phosphatidylcholine in gastric glands, up to 146 +/-
      11% of control (n = 6, P less than 0.05). On the other hand famotidine,
      ranitidine and cimetidine significantly decreased the incorporation to 73 +/- 8%,
      72 +/- 11%, 67 +/- 11% of control, respectively (n = 6, P less than 0.05, P less
      than 0.05, P less than 0.05). When the glands were pulsed with [3H] choline
      followed by incubation in the presence of teprenone or each H2RA for 180 min to
      see the effects of the agents on the limiting step of the phosphatidylcholine
      synthesis, teprenone also significantly stimulated [3H] choline incorporation
      into phosphatidylcholine, but each H2RA did not affect phosphatidylcholine
      biosynthesis any more. Teprenone stimulated CTP:phosphocholine
      cytidylyltransferase (CTF) from a basal value of 0.92 +/- 0.10 to 1.69 +/- 0.39
      (nmol/min/mg protein) (n = 3, P less than 0.05). These results suggest that
      teprenone may stimulate phosphatidylcholine biosynthesis through the activation
      of CTF, a late-limiting enzyme of PC biosynthesis, and H2RA may affect
      phosphatidylcholine synthesis by inhibiting choline transport or choline kinase
      in gastric glands.

PMID- 1979089
TI  - [Current status of pain treatment].

PMID- 1979090
TI  - Human cerebral malaria: association with erythrocyte rosetting and lack of anti
      rosetting antibodies.
AB  - Plasmodium falciparum isolates from 24 Gambian children with cerebral malaria and
      57 children with mild forms of the disease were assessed for their ability to
      form erythrocyte rosettes. All isolates from the children with cerebral malaria
      were able to form rosettes, whereas those from children with mild forms of the
      disease did not form rosettes, or had a significantly lower rosetting rate.
      Plasma of children with cerebral malaria lacked anti-rosetting activity, whereas
      plasma of children with mild disease could often disrupt rosettes in vitro. A
      monoclonal antibody to P falciparum histidine rich protein (PfHRP1/KP/KAHRP)
      disrupted rosettes of many of the isolates in vitro indicating that the rosetting
      ligand is relatively conserved compared with ligands associated with endothelial
      cytoadherence. The findings strongly support the hypothesis that erythrocyte
      rosetting contributes to the pathogenesis of cerebral malaria and suggest that
      anti-rosetting antibodies protect against cerebral disease.

PMID- 1979091
TI  - Community lifestyle characteristics and risk of acute lymphoblastic leukaemia in
      children.
AB  - High rates of leukaemia in children and young people have been associated with
      features of community isolation and population growth. Incidence data collected
      by two specialist registries were used to compare incidence rates at ward level
      with relevant ward characteristics derived from routine census and Ordnance
      Survey data for England and Wales. An excess risk of childhood acute
      lymphoblastic leukaemia (ALL) was found for wards which are farthest from large
      urban centres. The excess was greatest for wards of higher socioeconomic status
      and for children aged 1-7 years (the childhood peak), for which a two-fold excess
      was seen. These findings in general support the hypothesis that childhood
      leukaemia has an infectious aetiology.

PMID- 1979092
TI  - Inaccuracy of the Hawksley random zero sphygmomanometer.
AB  - To examine the accuracy of the Hawksley random zero sphygmomanometer two studies
      were done with subjects with a wide range of blood pressure. When readings made
      by one observer on the UK model of the Hawksley sphygmomanometer were compared
      with readings by two independent observers on separate mercury sphygmomanometers,
      the Hawksley device underestimated systolic readings by a mean (SD) of 2.0 (2.4)
      and 0.5 (3.6) mm Hg and diastolic readings by a mean of 3.7 (2.7) and 2.8 (2.9)
      mm Hg. When readings made on the UK and US models of the Hawksley
      sphygmomanometer were compared with those made on mercury sphygmomanometers, with
      observers exchanging devices half way during the experiment, the UK Hawksley
      device underestimated systolic pressure by a mean of 3.8 (SD 3.5) mm Hg and
      diastolic blood pressure by 7.5 (3.8) mm Hg; and the US model by 2.6 (3.4) mm Hg
      for systolic pressure and 6.2 (3.7) mm Hg for diastolic pressure. There was
      better agreement between two observers using standard sphygmomanometers than
      between an observer using the Hawksley random zero sphygmomanometer and an
      observer using a standard sphygmomanometer. Thus, the quantitative aspects of
      blood pressure in epidemiological and intervention studies in which the Hawksley
      random zero sphygmomanometer was used need re-evaluation. Moreover, the Hawksley
      random zero sphygmomanometer, in its present design, should not be used in
      hypertension research.

PMID- 1979093
TI  - Hepatitis C quantification and sequencing in blood products, haemophiliacs, and
      drug users.
AB  - The polymerase chain reaction (PCR) detected specific hepatitis C viral (HCV) RNA
      sequences in plasma from 15 of 21 haemophiliacs (12 HCV-antibody positive) and 7
      of 27 intravenous drug users (13 HCV-antibody positive). Quantification of RNA
      positive samples showed high levels of HCV (10(5) to 10(6) copies of RNA/ml) in
      infected patients. HCV was more frequently found in haemophiliacs infected with
      human immunodeficiency virus (11/11 HIV-positive and 4/10 HIV-negative patients).
      HCV-RNA was detected in all batches of commercially available factor VIII tested
      and in low concentrations in some pools of plasma donations from volunteers.
      Factor VIII, manufactured from volunteer donations, was uniformly negative by
      PCR. Phylogenetic analysis of viral sequences showed two distinct groups: one was
      associated with intravenous drug users and the other with haemophiliacs infected
      with Scottish factor VIII preparations. Both were distinct from sequences found
      in commercially available factor VIII.

PMID- 1979094
TI  - Effacement of glomerular foot processes in kwashiorkor.
AB  - In a study of the pathogenesis of the oedema of kwashiorkor the ultrastructure of
      the kidneys from 6 children was examined shortly after they died from oedematous
      malnutrition. There was a generalised effacement of the glomerular epithelial
      cells onto the basement membrane. The filtration slits that remained were
      narrowed. The picture was similar to that seen in minimal-change nephrotic
      syndrome--but none of the children had albuminuria. The degree of effacement was
      statistically related to treatment with gentamicin. The findings suggest that
      there is a defect in the anionic charge of the glomerular basement membrane in
      oedematous malnutrition, that the membrane charge is more easily neutralised by
      cations such as gentamicin, and that, because proteinuria is not a feature of
      oedematous malnutrition, the proteinuria in other conditions associated with
      glomerular epithelial cell effacement (eg, minimal-change nephrotic syndrome) is
      due to something more complex than simple loss of charge.

PMID- 1979095
TI  - Childhood leukaemia: an infectious disease?

PMID- 1979096
TI  - Perinatal prophylaxis of tuberculosis.

PMID- 1979097
TI  - Reproductive health and mifepristone.

PMID- 1979098
TI  - Diffusion confusion.

PMID- 1979099
TI  - Edwin Chadwick and the world we live in.

PMID- 1979101
TI  - Solid tumours and wounds: transformed cells misunderstood as injured tissue?

PMID- 1979100
TI  - Pregnancy outcome after inadvertent ivermectin treatment during community-based
      distribution.
AB  - Ivermectin is the drug of choice for community-based treatment of onchocerciasis.
      Since pregnancy testing during mass distribution campaigns is not feasible, the
      safety of ivermectin in pregnancy must be established. During a 3-year study,
      ivermectin was distributed to the population of a rubber plantation (14,000
      people) in Liberia. Only 31% of women were aware of their pregnancy status during
      the first month; it was calculated that about half of women in the first
      trimester of pregnancy are likely to be treated inadvertently. 203 children born
      to women inadvertently treated during pregnancy were identified. In this limited
      sample, there was no significant difference in birth defects between treated and
      untreated mothers in the same population or compared with a reference population.
      Children of treated and untreated mothers showed no difference in developmental
      status or disease patterns. Further surveillance is necessary; however, since no
      major effects of ivermectin on pregnancy outcome were detected, there seems no
      need to change existing strategies of ivermectin distribution.

PMID- 1979102
TI  - Natural foodborne toxicants.

PMID- 1979103
TI  - No-fault compensation.

PMID- 1979105
TI  - Compensation for HIV-infected haemophiliacs.

PMID- 1979104
TI  - Us and them--reality and fantasy with HIV.

PMID- 1979106
TI  - Beta-blockers and variceal haemorrhage.

PMID- 1979107
TI  - Free haemoglobin and pre-eclampsia.

PMID- 1979108
TI  - Chiropractors and low back pain.

PMID- 1979109
TI  - Cholecystectomy in Saudi Arabia.

PMID- 1979110
TI  - What is the "true" antigen for antiphospholipid antibodies?

PMID- 1979111
TI  - Haematological effects of interleukin-1.

PMID- 1979112
TI  - Hysterical paralysis.

PMID- 1979113
TI  - Is reduced salivary flow normal in old people?

PMID- 1979114
TI  - Airborne mite antigen.

PMID- 1979115
TI  - Cyclophosphamide for chronic relapsing thrombotic thrombocytopenic purpura.

PMID- 1979116
TI  - Ciprofloxacin and pseudomembranous colitis.

PMID- 1979117
TI  - Bcl-2 protein expression in follicular lymphomas in absence of 14;18
      translocation.

PMID- 1979118
TI  - Mianserin, agranulocytosis, and suicide.

PMID- 1979119
TI  - Pulmonary syndrome and intravenous high-dose desferrioxamine.

PMID- 1979120
TI  - Drug abusers in prison.

PMID- 1979121
TI  - The invisible middle ground.

PMID- 1979122
TI  - Day-case surgery.

PMID- 1979123
TI  - Abortion.

PMID- 1979124
TI  - Clinical trials in paediatrics.

PMID- 1979125
TI  - Rhabdomyolysis and temperature.

PMID- 1979126
TI  - Heterosexual transmission of HIV-1 in women in Austria.

PMID- 1979127
TI  - Oral treatment of late borreliosis with roxithromycin plus co-trimoxazole.

PMID- 1979128
TI  - No evidence for HIV-2 infection in Uganda.

PMID- 1979129
TI  - Fatal case of 2',3'-dideoxyinosine-associated pancreatitis.

PMID- 1979130
TI  - Hepatitis C virus RNA in saliva.

PMID- 1979131
TI  - Monoclonal ELISA to detect active tuberculosis.

PMID- 1979132
TI  - Psychology of cancer therapists.

PMID- 1979133
TI  - Screening for HTLV-I.

PMID- 1979134
TI  - Safety of testosterone enanthate.

PMID- 1979135
TI  - Tumorigenic effect of testosterone.

PMID- 1979136
TI  - Dynorphin1-17 can enhance or impair retention of an inhibitory avoidance response
      in rats.
AB  - The possible effects of subcutaneous administration of dynorphin1-17 on retention
      of an inhibitory avoidance behavior have been studied in rats. Post-training or
      pre-test administration of dynorphin1-17 in doses of 25 or 50 micrograms/kg
      facilitated retention performance in rats subjected to a footshock of 0.2 mA n
      the acquisition trial. However, the same doses of the opioid peptide exerted a
      deleterious effect on retention performance when a footshock of 0.4 mA was used
      after either post-training or pre-test administration. Post-training injection of
      the kappa-receptor antagonist MR-2266 in doses of 0.5, 1 or 2.5 mg/kg failed to
      affect retention behavior. However, the previous administration of 2.5 mg/kg of
      MR-2266 prevented the facilitatory effect exerted by dynorphin1-17 after post
      training, as well as after pre-test administration. Our results suggest that
      dynorphin1-17 may be involved in modulating the consolidation, as well as the
      retrieval, of recently acquired information.

PMID- 1979137
TI  - Effect of prolonged 5-hydroxytryptamine uptake inhibition by paroxetine on
      cortical beta 1 and beta 2-adrenoceptors in rat brain.
AB  - The effects of prolonged (21 day) oral administration of the antidepressants
      paroxetine (0.9 to 8.9 mg/kg/day) and amitriptyline (2.7 to 27 mg/kg/day), on rat
      brain cortical beta 1- and beta 2-adrenoceptor numbers and affinities were
      investigated using [3H]-CGP 12177. Although amitriptyline, 27 mg/kg, caused a
      significant (p less than 0.05) 20% reduction in the number of beta 1
      adrenoceptors, paroxetine, at doses up to 8.9 mg/kg p.o., did not influence
      binding of [3H]-CGP 12177 to cortical beta 1- or beta 2-adrenoceptors. This study
      with paroxetine provides further evidence that the down-regulation of central
      beta 1-adrenoceptors in rat brain after repeated administration is not a property
      of all antidepressant drugs.

PMID- 1979138
TI  - Phorbol ester suppression of opioid analgesia in rats.
AB  - Protein kinase C (PKC) has been shown to be an important substrate in
      intracellular signal transduction. Very little is known concerning its possible
      role in mediating opiate-induced analgesia. In the present study, 12-O
      tetradecanoylphorbol 13-acetate (TPA), a selective activator of PKC, was injected
      intrathecally (ith) to assess its influence on the analgesia induced by
      intrathecal injection of the mu opioid agonist PL017, the delta agonist DPDPE and
      the kappa agonist 66A-078. Radiant heat-induced tail flick latency (TFL) was
      taken as an index of nociception. TPA in the dose of 25-50 ng, which did not
      affect the baseline TFL, produced a marked suppression of opioid antinociception,
      with a higher potency in blocking mu and delta than the kappa effect. In
      addition, mu and delta agonists induced remarkable decreases in spinal cyclic AMP
      (cAMP) content whereas the kappa effect was weak. The results suggest a cross
      talk between the PKC system and the signal transduction pathway subserving opioid
      analgesia.

PMID- 1979139
TI  - [Nutrition and behavior in pediatrics].
AB  - The influence of diet on human behaviour was first postulated several centuries
      ago, albeit in terms of a magical interpretation of life. Due to our improved
      knowledge of the basic science, we are now able to provide experimental proof to
      support this concept. Some opinions, which were once believed to be true, have
      now been disproved, whereas others have been reconfirmed in physiological terms.
      This paper aims to evaluate the state of the art in particular with regard to
      pediatrics. It is now certain that some amino-acids in the diet can influence
      brain activity by enhancing or reducing the metabolic rates of different
      neurotransmitters. A modulating effect on the brain has even been suggested with
      regard to some vitamins and minerals, but data on this aspect are still under
      evaluation. On the other hand, no data have yet been reported to support the
      hypothesis of a specific etiological role played by any nutrient in the
      development of behavioural disturbances.

PMID- 1979140
TI  - Human T-lymphotropic virus type I screening in volunteer blood donors--United
      States, 1989.
AB  - On November 29, 19898, the Food and Drug Administration (FDA) issued
      recommendations to screen all whole blood donations in the United States for
      human T-lymphotropic virus type I (HTLV-1). This report summarizes results of the
      first 13 months of screening (December 1988 through December 1989) by the
      American Red Cross (ARC) and the Council of Community Blood Centers (CCBC).

PMID- 1979141
TI  - Identification of Brassica oleracea monosomic alien chromosome addition lines
      with molecular markers reveals extensive gene duplication.
AB  - Chromosomes of Brassica oleracea (2n = 18) were dissected from the resynthesized
      amphidiploid B. napus Hakuran by repeated backcrosses to B. campestris (2n = 20),
      creating a series of monosomic alien chromosome addition line plants (2n = 21).
      Using morphological, isozyme and restriction fragment length polymorphism markers
      (RFLPs), 81 putative loci were identified. Of nine possible synteny groups, seven
      were represented in the 25 monosomic addition plants tested. Sequences homologous
      to 26% of the 61 DNA clones utilized (80% were cDNA clones) were found on more
      than one synteny group, indicating a high level of gene duplication. Anomalous
      synteny associations were detected in four 2n = 21 plants. One of these plants
      showed two markers from one B. oleracea chromosome associated with a second
      complete B. oleracea synteny group, suggesting translocation or recombination
      between non-homologous chromosomes in Hakuran or the backcross derivatives. The
      other three 2n = 21 plants each contained two or more B. oleracea synteny groups,
      suggesting chromosome substitution.

PMID- 1979143
TI  - Molecular changes in protoplast-derived rice plants.
AB  - To determine whether regeneration of rice plants from protoplast culture induces
      DNA polymorphisms, progeny plants from direct regenerants of such cultures were
      examined for restriction fragment length polymorphisms (RFLP analysis).
      Significantly increased levels of DNA polymorphism were found compared with those
      in non-tissue culture control plants. Analysis with gene sequences representative
      of different functional domains, revealed that such polymorphisms are apparently
      widespread and not associated with any particular region. Analysis by comparative
      digestion with both methylation-sensitive and insensitive restriction enzymes
      revealed that methylation changes cannot be regarded as a major factor in the
      induction of these DNA polymorphisms.

PMID- 1979142
TI  - Premeiotic disruption of the Neurospora crassa malate synthase gene by native and
      divergent DNAs.
AB  - Repeat-induced point mutation (RIP) has been used to generate new mutations in
      the previously uncharacterised gene for malate synthase in Neurospora crassa.
      Molecular clones carrying the am (NADP-glutamate dehydrogenase) gene and the
      malate synthase gene from either N. crassa or Aspergillus nidulans have been
      introduced into Neurospora as ectopic duplicate copies by transformation,
      selecting for the am+ function in a deletion host. A number of meiotic progeny
      derived from these transformants were unable to use acetate as sole carbon
      source, yielded no detectable malate synthase activity and demonstrated extensive
      cytosine methylation of their duplicated sequences. The new locus has been
      designated acu-9 and has been assigned to linkage group VII.

PMID- 1979144
TI  - Homomeric GluR1 excitatory amino acid receptors expressed in Xenopus oocytes.
AB  - The GluR1 cDNA clone encodes a functional excitatory amino acid receptor
      (Hollmann et al., Nature 342: 643-648 (1989]. We have studied the pharmacological
      properties of this homomeric (single subunit) receptor expressed in Xenopus
      oocytes and compared these properties with those of receptors encoded by rat
      forebrain mRNA. (RS)-alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionate,
      quisqualate, and glutamate were partial agonists at both GluR1 and forebrain non
      N-methyl-D-aspartate (-NMDA) receptors. The potency of the agonists kainate,
      domoate, and glutamate was higher, and that of the antagonists 6-cyano-7-nitro
      quinoxalinedione and 6,7-dichloro-3-hydroxy-2-quinoxaline carboxylic acid lower,
      for GluR1 receptors as compared with forebrain non-NMDA receptors. The GluR1
      receptor differed strikingly from forebrain-derived non-NMDA receptors, however,
      in that it exhibited slow, calcium-dependent desensitization. Thus, most
      properties of the GluR1 receptor are similar but not identical to those of non
      NMDA receptors expressed from forebrain mRNA. These results indicate that the
      ligand recognition sites on GluR1 homomeric receptors are subtly different from
      those of non-NMDA receptors expressed from a mixture of forebrain mRNA.

PMID- 1979145
TI  - Mechanism of the cardiotoxic action of palytoxin.
AB  - Palytoxin (PTX) is a non-12-O-tetradecanoylphorbol-13-acetate-type tumor promoter
      that has potent cardiotoxic properties. In embryonic chick ventricular cells, PTX
      increased [Ca2+]i (K0.5 = 5 nM) in a manner that was dependent on the presence of
      extracellular Ca2+. The action of PTX was not consequent to its depolarizing
      action, to the opening of voltage-dependent Ca2+ channels, to an intracellular
      Na+ load, or to intracellular acidification. Flow cytometric analysis of the
      [Ca2+]i distribution in PTX-treated cells showed that only the largest
      ventricular cells responded to the toxin. All ventricular cells responded to PTX
      by intracellar acidification. PTX also increased 22Na+ uptake by cardiac cells
      (K0.5 = 100 nM) via a pathway that was sensitive to 3,4-dichlorobenzamil (K0.5 =
      8 microM), suggesting a possible involvement of the Na+/Ca2+ antiporter. We
      conclude that the action of PTX in chick cardiac cells is distinct from that in
      erythrocytes or in fibroblasts and that it likely involves several distinct
      mechanisms. A primary action of PTX could be to open a Ca2+ uptake pathway in the
      plasma membrane, which would then trigger 22Na+ uptake by the Na+/Ca2+
      antiporter.

PMID- 1979146
TI  - Targets of homeotic gene control in Drosophila.
AB  - The homeotic gene Ultrabithorax (Ubx) encodes homeodomain-containing
      transcription factors that determine segmental identity in Drosophila. Here, an
      immunopurification procedure is described that enriches for embryonic chromatin
      fragments containing binding sites for Ubx protein. In two cases these binding
      sites are located near embryonic transcription units regulated by the Ubx locus
      in vivo. Thus, these transcripts may correspond to Ubx target genes involved in
      elaborating segment-specific developmental pathways.

PMID- 1979148
TI  - Developmental biology. Fly fishing downstream.

PMID- 1979147
TI  - (Mg-ATP)-dependent self-assembly of molecular chaperone GroEL.
AB  - The important Escherichia coli heat-shock protein GroEL of relative molecular
      mass 57,259 is a typical molecular chaperone. It possesses ATPase activity and
      interacts in ATP-driven reactions with non-folded proteins to stimulate their
      correct folding and/or assembly by preventing the formation of improper protein
      structures or aggregates. As GroEL is isolated and functions as a 20-25S
      tetradecameric particle (GroELp), the question arises--what is the mechanism of
      its own assembly? Here we show the (Mg-ATP)-dependent self-stimulation ('self
      chaperoning') in vitro of GroELp reassembly from its monomeric state.

PMID- 1979149
TI  - The effect of calcium in visual systems.

PMID- 1979150
TI  - Serum activities of AP, gamma-GT, G1DH and GPT in the first four days after bile
      duct obstruction and ethionine in the rat.
AB  - Following sham operation and bile duct obstruction (BDO), Wistar rats received
      ethionine, which inhibits protein synthesis in the liver. Earlier studies
      revealed, that the increase of activity of AP after BDO is the result of a de
      novo-synthesis of enzyme protein in the liver. With regard to serum activities of
      the enzymes G1DH, GPT and gamma-GT, no influence of de novo-synthesis after BDO
      has so far been certified, but these enzymes have only been investigated in the
      early phase after BDO, for up to 24 h under protein synthesis inhibition. In the
      present study, the protein synthesis inhibition was extended up to the fourth day
      after BDO. Signs of de novo-synthesis after BDO could also be detected in G1DH,
      GPT and gamma-GT.

PMID- 1979151
TI  - Very low calorie diets and recently developed anti-obesity drugs for treating
      overweight in non-insulin-dependent diabetics.

PMID- 1979152
TI  - Insulinomas in MEN-I patients: early detection and treatment of insulinomas in
      patients with the multiple endocrine neoplasia syndrome type-I.
AB  - In the multiple endocrine neoplasia syndrome type I (MEN-I syndrome), periodic
      screening of patients and their close relatives may improve prognosis and life
      expectancy. Although there is diffuse involvement of the pancreas with
      microadenomatosis, insulinomas in the MEN-I syndrome usually occur as single
      tumours. This is illustrated here by two patients with insulinomas and the MEN-I
      syndrome. Preoperative localization of the tumours was achieved accurately by
      digital subtraction angiography combined with dynamic computerized tomography
      after a bolus injection of contrast medium. At present, two and three years after
      elective surgery both patients are asymptomatic. The early detection and
      treatment of insulinomas is extremely important because of the high risk of
      cerebral damage associated with late diagnosis. Periodic investigation of MEN-I
      family members can promote the early diagnosis and treatment of insulinomas,
      especially in young patients, whose life expectancy and quality of life may be
      improved.

PMID- 1979153
TI  - A non-opioid pattern characterizes inhibition of growth hormone releasing peptide
      binding by dynorphin-related peptides.
AB  - GHRP-6 (His-D-Trp-Ala-Trp-D-Phe-LysNH2; SK&F 110679) is a hexapeptide that
      specifically releases growth hormone. Although derived from methionine
      enkephalin, 3H-SK&F 110679 binding profiles suggest that it retains little mu or
      delta opioid activity. In the present study, dynorphin A was a potent inhibitor
      of SK&F 110679 binding. However, detailed structure-activity studies using
      dynorphin-related compounds suggest that the interaction between SK&F 110679 and
      dynorphin was non-opioid in nature. The non-opioid peptide des-Tyr-dynorphin was
      virtually as potent an inhibitor of 3H-SK&F 110679 binding as the intact
      dynorphin peptide. Additionally, the non-peptide, kappa selective ligand U-50,488
      was a very weak inhibitor of 3H-SK&F 110679 binding. Since dynorphin but not U
      50,488 has been reported to release growth hormone, the present results suggest
      that a non-opioid dynorphin site participates in SK&F 110679's growth hormone
      releasing action.

PMID- 1979154
TI  - Intrahypothalamic injection of somatostatin, not GRF, stimulates prolactin
      secretion.
AB  - The distribution of somatostatin and growth hormone releasing factor (GRF) fibres
      in the hypothalamus suggests that they may be involved in physiological functions
      in addition to growth hormone control. GRF or somatostatin were stereotaxically
      injected into anterior or basal hypothalamic regions of unanesthetized male rats
      and effects on plasma prolactin measured. Somatostatin caused a small,
      significant, dose-responsive stimulation of prolactin secretion when injected in
      both hypothalamic regions, while GRF was without effect. Somatostatin may
      therefore have a minor intrahypothalamic role in regulating prolactin.

PMID- 1979155
TI  - Effects of acute and chronic cocaine administration on somatostatin level and
      binding in the rat brain.
AB  - The effects of acute and chronic cocaine (40 mg/Kg i.p.) in vivo administration,
      on 125I-Tyr11-somatostatin binding and somatostatin-like immunoreactivity (SLI)
      in the rat frontoparietal cortex, hippocampus and olfactory bulb were explored.
      Acute and chronic cocaine administration did not affect the levels of SLI in the
      three brain areas studied. Acute cocaine administration resulted in an 55% and
      32% decrease in the total number of specific somatostatin receptors in the
      hippocampus and olfactory bulb respectively, but not in the frontoparietal
      cortex. Somatostatin receptor affinity increased in the hippocampus and was
      unaltered in frontoparietal cortex and olfactory bulb. After two weeks of daily
      cocaine injections the somatostatin binding in the hippocampus and olfactory bulb
      returned to control values. The in vitro addition of cocaine to a brain membrane
      preparation obtained from untreated rats did not markedly affect somatostatin
      binding characteristics. These results are suggestive of a possible role for
      somatostatin in the limbic structures as a response to cocaine administration.

PMID- 1979156
TI  - Two actions of vasopressin on neurons in the rat ventral hippocampus: a
      microiontophoretic study.
AB  - Vasopressin (VP), applied by brief iontophoretic pulses on ventral hippocampus
      neurons in vivo, excited approximately 30% of the neurons tested. Glutamate (Glu)
      and acetylcholine (ACh) excited nearly all neurons recorded. A selective
      antagonist of vasopressin V1 receptors suppressed the VP-induced excitation and,
      in addition, suppressed the excitations induced by Glu but not those by ACh. The
      specificity of the action in the brain of this VP antagonist must therefore be
      doubted. Two excitatory amino acid antagonists, D(-)-2-amino-5-phosphonovaleric
      acid (2APV) and glutamic acid diethyl ester (GDEE), suppressed the responses to
      Glu and also those to VP. ACh excitations, tested in the same neurons, were
      little affected by 2APV and GDEE. The remaining 70% of VH neurons were not
      excitable with VP. However, the responses of these neurons to Glu but not to Ach,
      increased markedly both while the peptide was released and for tens of minutes
      thereafter. The increase in Glu responses induced by VP could not be prevented by
      the VP or excitatory amino acid receptor antagonists applied before the peptide.
      The possibility that the excitation and the potentiation of Glu responses caused
      by VP originated from two different actions of the peptide is discussed.

PMID- 1979157
TI  - Ventromedial hypothalamic somatostatin may affect gastric somatostatin
      concentration in rats.
AB  - Changes in the somatostatin-like immunoreactivity (SLI) concentrations in gastric
      antral mucosa were detected by RIA following microinjections of synthetic
      somatostatin (SS) or cysteamine (CSH) into the ventromedial nucleus of the
      hypothalamus (VMH). SLI concentrations in the antral mucosa were increased by
      60.8% (p less than 0.001) and 42.3% (p less than 0.05), respectively, one and
      four hours after microinjection of somatostatin (0.5 microgram/0.5 microliter)
      into the VMH, and decreased by 32.6% (p less than 0.05) four hours after
      microinjection of cysteamine (15 microgram/0.5 microliter) into the VMH.
      Moreover, microinjection of somatostatin (0.5 microgram/0.5 microliter) into the
      VMH could only elicit an increase of 16.0% (p less than 0.05) in the SLI
      concentration in the antral mucosa one hour after bilateral subdiaphragmatic
      vagotomies, but still produced an increase of 120.0% (p less than 0.05) following
      celiac ganglionectomies. In conclusion, somatostatin (exogenous and endogenous)
      in the VMH seems to affect the gastric somatostatin levels via the vagal nerves.

PMID- 1979158
TI  - Dental examinations prior to elective surgery under anesthesia.
AB  - It is important to involve the patient's general dentist in the preoperative
      management, since routine dental examinations are performed more frequently than
      surgery. If the dentist learns from the patient that he or she will be undergoing
      surgery, the dentist should stress the importance of stabilizing or removing any
      loose teeth or prostheses prior to surgery. In most medical centers today,
      patients undergoing elective surgery are seen by the anesthesiologist prior to
      their date of surgery for preadmission testing. A review of the patient's medical
      history is obtained and physical examination is performed. The anesthesiologist
      examines the patient for difficulty with opening the mouth, and for any loose
      crowns or dentures. If there are dental problems that should be corrected, the
      patient should be requested to visit his/her dentist prior to surgery. This will
      help prevent problems during the administration of general anesthesia. Reviewing
      the literature, it is difficult to obtain definite statistics on the incidence of
      dental complications secondary to general anesthesia. Most references agree that
      damage to the teeth and dental appliances is the most common complication of
      intubation. Damaged teeth result in the largest number of lawsuits filed against
      anesthesiologist. One review of anesthesia-related claims reports that 17 percent
      of the claims are due to damage to the teeth or dental prosthesis. Several
      authors had advocated the use of devices to help protect the dentition during the
      surgery. Most of these devices temporarily splint or protect the teeth from
      trauma during intubation and extubation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1979159
TI  - The v-erb A oncogene causes repression of erythrocyte-specific genes and an
      immature, aberrant differentiation phenotype in normal erythroid progenitors.
AB  - We have compared the effects of the v-erb A oncogene on proliferation and
      differentiation of normal erythroid progenitors with those of tyrosine kinase
      oncogenes, e.g. v-sea. For this, a v-erb A retrovirus containing the neomycin
      resistance gene as a selectable marker or, alternatively, a v-erb A-ts v-sea
      retrovirus were used to infect normal bone marrow cells. V-erb A induced the
      outgrowth of immature, erythropoietin(EPO)-dependent erythroid cells from
      infected bone marrow which ceased to proliferate and disintegrated after 9 to 18
      divisions. In contrast, ts-v-sea erythroblasts grew for the expected 25 to 40
      population doublings in the absence of EPO. Transcription of the erythrocyte
      genes carbonic anhydrase II and erythrocyte anion transporter was significantly
      inhibited in v-erb A infected erythroblasts, indicating that v-erb A alone was
      sufficient for the repression of the erythrocyte-specific genes observed in AEV
      transformed leukemic cells. A detailed analysis of the differentiation phenotype
      induced by v-erb A in erythroblasts (in the presence or absence of a temperature
      inactivated ts sea oncogene) indicates that v-erb A-erythroblasts express a
      partially mature, aberrant phenotype characterized by the coexpression of mature
      and immature differentiation antigens. This phenotype clearly differs from that
      induced by tyrosine kinase oncogenes in erythroid cells.

PMID- 1979160
TI  - Mutations in the p53 gene are frequent in primary, resected non-small cell lung
      cancer. Lung Cancer Study Group.
AB  - The p53 gene has been implicated as a tumor suppressor gene with mutations found
      in common human cancers. We examined 51 early stage, primary, resected non-small
      cell lung cancer specimens using an RNAase protection assay and cDNA sequencing.
      Mutations changing the p53 coding sequence were found in 23/51 (45%) tumor
      specimens, but not in the corresponding normal lung, were distributed between
      codons 132 to 283, and included tumors with and without 17p allele loss. Fifteen
      of the 23 mutations lay in the predicted binding regions for SV40 large T
      antigen, and 14 were located in regions highly conserved between species. G to T
      transversions were a common result of p53 mutations in lung cancer compared to
      other cancers suggesting exposure to different mutagens. In univariate and
      multivariate analysis the presence of p53 mutations was associated with younger
      age and squamous histology. However, the presence of p53 mutations was not
      significantly associated with tumor stage, nodal status or sex and was found in
      all histologic types of lung cancer. We conclude that somatic mutations in the
      p53 gene play an important role in the pathogenesis of early stage non-small cell
      lung cancer.

PMID- 1979161
TI  - Characterization of descending inhibition and facilitation from the nuclei
      reticularis gigantocellularis and gigantocellularis pars alpha in the rat.
AB  - Descending influences on the spinal nociceptive tail-flick (TF) reflex produced
      by focal electrical stimulation and glutamate microinjection in the nuclei
      reticularis gigantocellularis (NGC) and gigantocellularis pars alpha (NGC alpha)
      were examined and characterized in rats lightly anesthetized with pentobarbital.
      Both inhibition and facilitation of the TF reflex were produced by electrical
      stimulation at identical sites in the NGC/NGC alpha; glutamate microinjection
      only inhibited the TF reflex. The chronaxie of stimulation for inhibition of the
      TF reflex was 169 +/- 28 microseconds. Inhibition of the TF reflex by stimulation
      was produced throughout the NGC and NGC alpha; intensities of stimulation for
      inhibition were least in the ventral NGC and in the NGC alpha. At threshold
      intensities of stimulation, inhibition of the TF reflex did not outlast the
      period of stimulation. Facilitation of the TF reflex was produced at many of the
      same sites at which stimulation inhibited the TF reflex, but always at lesser
      intensities of stimulation (mean, 10 microA vs. 43 microA for inhibition, n =
      25). Stimulation in the NGC/NGC alpha at threshold intensities for facilitation
      or inhibition of the TF reflex did not significantly affect blood pressure.
      Strength-duration characterization of electrical stimulation and microinjection
      of glutamate into identical sites in the NGC and NGC alpha suggest that
      descending inhibition of the TF reflex results from activation of cell bodies in
      the NGC and NGC alpha.

PMID- 1979162
TI  - DNA polymorphisms amplified by arbitrary primers are useful as genetic markers.
AB  - Molecular genetic maps are commonly constructed by analyzing the segregation of
      restriction fragment length polymorphisms (RFLPs) among the progeny of a sexual
      cross. Here we describe a new DNA polymorphism assay based on the amplification
      of random DNA segments with single primers of arbitrary nucleotide sequence.
      These polymorphisms, simply detected as DNA segments which amplify from one
      parent but not the other, are inherited in a Mendelian fashion and can be used to
      construct genetic maps in a variety of species. We suggest that these
      polymorphisms be called RAPD markers, after Random Amplified Polymorphic DNA.

PMID- 1979163
TI  - Nucleotide sequence of the Bacillus subtilis IMP dehydrogenase gene.

PMID- 1979164
TI  - Deletion in prion protein gene in a Moroccan family.

PMID- 1979165
TI  - A BamHI RFLP in the human arylsulfatase A gene.

PMID- 1979166
TI  - A TaqI RFLP for the human arylsulfatase A gene.

PMID- 1979167
TI  - [Regression of left ventricular hypertrophy with antihypertensive treatment].
AB  - The presence of left ventricular hypertrophy (LVH) is of poor prognosis in
      essential arterial hypertension, but it may regress under antihypertensive
      treatment. Angiotensin-converting enzyme inhibitors, calcium antagonists,
      centrally acting antihypertensive agents and beta-blockers with low intrinsic
      sympathomimetic activity constantly reduce the left ventricular mass. This stands
      in contrast with diuretics and vasodilators which induce stimulation of the
      sympathetic and/or renin-angiotensin systems and usually have no effect on LVH.
      Animal experiments have shown that regression of LHV has no adverse effect on the
      myocardial changes aimed at correcting the LVH-associated abnormalities (collagen
      content, changes in isomyosins, density of beta-adrenergic receptors, etc.) and
      that it improves the coronary haemodynamics disturbed by LVH. In clinical
      practice, reducing the ventricular mass does not modify the left ventricular
      systolic function, usually improves the diastolic function precociously altered
      by LVH and seems to reduce the LVH-induced ventricular hyperexcitability. The
      regression of LVH under antihypertensive treatment should result in a lesser
      cardiovascular risk in hypertensive patients.

PMID- 1979168
TI  - Tissue-specific transformation by epidermal growth factor receptor: a single
      point mutation within the ATP-binding pocket of the erbB product increases its
      intrinsic kinase activity and activates its sarcomagenic potential.
AB  - Avian c-erbB is activated to a leukemia oncogene following truncation of its
      amino-terminal, ligand-binding domain by retroviral insertion. The insertionally
      activated transcripts encode protein products that have constitutive tyrosine
      kinase activity and that can induce erythro-leukemia but not sarcomas. We have
      found that a single point mutation within the ATP-binding pocket of the tyrosine
      kinase domain in this truncated molecule can increase the ability of this
      oncogene to induce anchorage-independent growth of fibroblasts in vitro and
      fibrosarcoma formation in vivo. Associated with this increased transforming
      potential is a corresponding increase in the kinase activity of the mutant erbB
      protein product. The mutation, which converts a valine to isoleucine at position
      157 of the insertionally activated c-erbB product, is at a residue that is highly
      conserved within the protein kinase family. To our knowledge, this is the first
      demonstration of a point mutation in the ATP-binding pocket that activates a
      tyrosine kinase.

PMID- 1979169
TI  - Postsynaptic Hebbian and non-Hebbian long-term potentiation of synaptic efficacy
      in the entorhinal cortex in slices and in the isolated adult guinea pig brain.
AB  - Long-term potentiation (LTP) was investigated in the mammalian entorhinal cortex
      by using two in vitro preparations, the isolated brain and the entorhinal cortex
      slice. Hebbian and non-Hebbian types of LTP appear to be present in layer II
      entorhinal cortex cells as demonstrated using two protocols: (i) tetanic
      stimulation of the piriform-entorhinal cortex afferent pathway to generate
      homosynaptic potentiation and (ii) postsynaptic subthreshold rhythmic membrane
      potential manipulation not paired to presynaptic activation, which gives rise to
      non-Hebbian LTP. The induction and the expression of both types of LTP were found
      to be dependent on activation of N-methyl-D-aspartate receptors as shown by their
      sensitivity to the receptor agonist D-2-amino-5-phosphonovalerate. This is in
      contrast to LTP in the hippocampus [Zalutsky, R. A. & Nicoll, R. A. (1990)
      Science 248, 1619-1624], where LTP is expressed by quisqualate receptors. Since,
      in the entorhinal cortex, LTP is linked to a selective increase of the N-methyl-D
      aspartate-receptor-mediated synaptic responses, this enhancement is most likely
      due to postsynaptic factors.

PMID- 1979170
TI  - Glucocorticoids locally disrupt an array of positioned nucleosomes on the rat
      tyrosine aminotransferase promoter in hepatoma cells.
AB  - Transcriptional activation by steroid hormones is often associated with the
      appearance of a DNase I hypersensitive site resulting from a local alteration of
      the nucleoprotein structure of the promoter. For the mouse mammary tumor virus
      long terminal repeat, a viral promoter under glucocorticoid control, a model has
      been proposed: the appearance of the hormonodependent DNase I hypersensitive site
      reflects the displacement of a single precisely positioned nucleosome associated
      with the glucocorticoid responsive elements. To determine if such a mechanism is
      of general relevance in transcriptional activation by steroid hormones, we have
      investigated the nucleosomal organization of the rat tyrosine aminotransferase
      promoter over a 1-kilobase region that contains the glucocorticoid regulatory
      target. This region displays a hormonodependent DNase I hypersensitive site. In
      the absence of hormone, micrococcal nuclease digestion of nuclei demonstrates the
      presence of positioned nucleosomes, with cutting sites centered around positions 
      3080, -2900, -2700, -2800, -2255, and -2040. Treatment of the cells with
      dexamethasone induces a disruption of the chromatin structure over a relatively
      short stretch of DNA (approximately positions -2400 to -2650) that overlaps two
      nucleosomes. These observations suggest a strong similarity in the role of
      chromatin structure in glucocorticoid-dependent transcriptional activation of
      mouse mammary tumor virus and tyrosine aminotransferase promoters.

PMID- 1979173
TI  - High-dose trimipramine in acute schizophrenia. Preliminary results of an open
      trial.
AB  - Trimipramine and clozapine show some similarities in receptor-binding profiles.
      Both have the same dissociation constant for D2-receptors and marked binding
      potencies for H1-receptors and muscarinic acetylcholine receptors. Based on these
      similarities an antipsychotic efficacy of trimipramine might be postulated. To
      generate hypotheses 15 schizophrenic patients with a BPRS total score of at least
      50 were treated with trimipramine up to 400 mg per day. Four patients
      deteriorated under this treatment and had to be withdrawn from the study between
      the 4th and the 10th day. One patient stopped participating after the 15th day
      due to lack of improvement. These drop-outs showed a mean impairment in BPRS
      total score from 56 at baseline to 66 at endpoint. Ten patients were treated for
      4 to 5 weeks successfully and improved on the BPRS from 57 at baseline to 31 at
      endpoint. High-dose trimipramine was tolerated well. In schizophrenic patients
      the expected sedative effect was small. One patient developed a modest
      parkinsonism, no acute dystonia was seen.

PMID- 1979171
TI  - Primary structure of keratinocyte transglutaminase.
AB  - The nucleotide and deduced amino acid sequences of the coding regions of human
      and rat keratinocyte transglutaminases (protein-glutamine: amine gamma
      glutamyltransferase; EC 2.3.2.13) have been determined. These yield proteins of
      approximately 90 kDa that are 92% identical, indicative of the conservation of
      important structural features. Alignments of amino acid sequences show
      substantial similarity among the keratinocyte transglutaminase, human clotting
      factor XIII catalytic subunit, guinea pig liver tissue transglutaminase, and the
      human erythrocyte band-4.2 protein. The keratinocyte enzyme is most similar to
      factor XIII, whereas the band-4.2 protein is most similar to the tissue
      transglutaminase. A salient feature of the keratinocyte transglutaminase is its
      105-residue extension beyond the N terminus of the tissue transglutaminase. This
      extension and the unrelated activation peptide of factor XIII (a 37-residue
      extension) appear to be added for specialized functions after divergence of the
      tissue transglutaminase from their common lineage.

PMID- 1979174
TI  - Reports of workshops held at the 16th Arbeitsgemeinschaft fur Neuro
      Psychopharmakologie und Pharmakopsychiatrie (AGNP) Congress, October 4-7 1989, in
      Nuremberg, FRG.

PMID- 1979172
TI  - Tumor necrosis factor-induced degranulation in adherent human neutrophils is
      dependent on CD11b/CD18-integrin-triggered oscillations of cytosolic free Ca2+.
AB  - We have recently been able to correlate closely the "spontaneous" oscillatory
      activity of cytosolic free Ca2+ in adherent human neutrophils with the ability of
      tumor necrosis factor (TNF) to induce secretion of granule proteins from these
      cells. In the present work we show with a single-cell technique that
      preincubation of human neutrophils with antibodies to CD18, the common beta chain
      of leukocyte adhesion proteins, inhibits TNF-induced secretion of lactoferrin in
      a time- and concentration-dependent manner. Similar effects of CD18 antibodies
      were found on chemotactic factor (fMet-Leu-Phe)- but not on phorbol 12-myristate
      13-acetate-induced secretion, suggesting that cell-surface-receptor-mediated
      secretion is dependent on integrin-associated signals. Similarly, antibodies to
      CD11b (alpha chain of macrophage 1) also inhibited TNF- and fMet-Leu-Phe- but not
      phorbol 12-myristate 13-acetate-stimulated release of lactoferrin. Antibodies to
      CD11a (alpha chain of lymphocyte function-associated antigen 1) or CD11c (alpha
      chain of p150,95) had only a minimal effect on agonist-induced secretion. Data
      obtained in several laboratories, including our own, made us suspect that
      integrin interaction with the surface is responsible for the oscillatory activity
      of cytosolic free Ca2+ in adherent cells. Indeed, preincubation with antibodies
      to either CD18 or CD11b, but not to CD11c, inhibited the oscillations of
      cytosolic free Ca2+ in adherent neutrophils. This inhibitory effect was evident
      both as a reduction of the number of responding cells and as a reduction of the
      oscillatory activity in the cells. In conclusion, the oscillatory activity of
      cytosolic free Ca2+ in adherent neutrophils is mediated through the CD18/CD11b
      integrins. The generation of this Ca2+ signal may explain how adherence, by way
      of the integrins, changes the functional properties of the cell and enables TNF
      to induce secretion.

PMID- 1979175
TI  - Unaltered [3H]GBR-12935 binding after chronic treatment with dopamine active
      drugs.
AB  - Rats were injected intraperitoneally with haloperidol 0.5 mg/kg, raclopride 1
      mg/kg, bromocriptine 2.5 mg/kg, d-amphetamine 2.5 mg/kg, or cocaine 10 mg/kg
      twice daily for 21 days. The animals were sacrificed 72 h after last injection.
      Control rats were injected with saline, following the same schedule. The
      radioligand [3H]GBR-12935 was used as a presynaptic marker for dopamine neurites.
      There were no significant differences in [3H]GBR-12935 binding to striatum
      between drug-treated rats and controls.

PMID- 1979177
TI  - Influence of certain H1-blockers on the step-through active avoidance response in
      rats.
AB  - The inhibitory effects of some newly developed H1-blockers on the step-through
      active avoidance response in rats were studied in comparison with those of
      classical H1-blockers. Single administration of diphenhydramine, pyrilamine,
      promethazine and chlorpheniramine caused dose-related depressant effects on the
      active avoidance response. Ketotifen and azelastine caused less potent inhibition
      than the classical H1-blockers, while the effects of astemizole and oxatomide
      were almost negligible in suppressing the response. Following chronic
      administration of pyrilamine and promethazine, the acquisition of active
      avoidance response was significantly retarded compared with the control group,
      whereas new H1-blockers caused a somewhat but not significantly slower
      acquisition than the control group. Chronic administration of astemizole and
      oxatomide caused only transient suppression of the response. However, classical
      H1-blockers such as pyrilamine and promethazine caused sustained inhibition for
      as long as drug administration was continued.

PMID- 1979176
TI  - Effects of classical and novel agents in a MPTP-induced reversible model of
      Parkinson's disease.
AB  - A modified primate model of Parkinson's disease was developed to assess the
      effectiveness of various agents that act via dopamine, acetylcholine, serotonin
      or glutamate systems. Using a MPTP dosing regimen a reversible parkinsonian-like
      syndrome was produced in the marmoset. An obvious advantage of such a protocol is
      that it allows multiple drug studies to be undertaken in animals, without the
      need for prolonged anti-parkinsonian therapy to maintain their health. Results
      show that dopamine D2 agonists (bromocriptine, quinpirole, N,N-dipropyl,A,5,6
      DTN, (+)3PPP and PHNO), anti-muscarinics (atropine, scopolamine and benztropine),
      in addition to L-DOPA and nomifensine, all reduced the bradykinesia induced by
      MPTP. The D1 agonist SKF-38393 and the partial dopamine agonist (-)3PPP were both
      ineffective. Finally, agents with potential therapeutic use in Parkinson's
      disease were also tested. However, a glutamate antagonist (MK801) and three
      serotonin antagonists (ritanserin, ketanserin and ICI 170,809) were all unable to
      alter the MPTP effects, at the doses used in our study.

PMID- 1979179
TI  - Synergistic effects between D-1 and D-2 dopamine antagonists on catalepsy in
      rats.
AB  - The effect of selective D-1 and D-2 dopamine agonists on catalepsy induced by
      various dopamine antagonists was studied. A potent and selective D-2 antagonist,
      YM-09151 (YM-09151-2) at a dose of 1.2 mg/kg, SC and a selective D-1 antagonist,
      SCH 23390 at 1.0 mg/kg, SC induced catalepsy in rats. Mixed D-1/D-2 antagonists,
      haloperidol (HPD) and cis-flupentixol (FLU) also induced catalepsy at doses of
      2.0 and 0.8 mg/kg, SC, respectively. A mixed D-1/D-2 agonist, apomorphine (1.0
      mg/kg, SC), a selective D-2 agonist, bromocriptine (10 mg/kg, IP) and a
      muscarinic antagonist, scopolamine (1.0 mg/kg, SC), prevented or markedly reduced
      the incidence of catalepsy by the tested antagonists. In contrast, a selective D
      1 agonist, SKF 38393 (4.0 mg/kg, SC) did not reduce the cataleptogenic effects of
      HPD, FLU and SCH 23390, but did reduce the effect of YM-09151. Moreover, co
      administration of YM-09151 with SCH 23390 produced a marked increase in the
      incidence of catalepsy. The incidence seen after the combination of YM-09151 and
      SCH 23390 at low doses was significantly different from that seen after each drug
      alone at the doubled dose. Thus, D-1 and D-2 antagonists potentiated each other's
      effect in producing catalepsy. These results suggest an important role of both D
      1 and D-2 receptors in the catalepsy and the existence of synergistic effects of
      D-1 and D-2 receptor blockade.

PMID- 1979178
TI  - Drug-induced purposeless chewing: animal model of dyskinesia or nausea?
AB  - Drug-induced purposeless chewing movements in rodents are often considered to
      represent movement disorders or dyskinesias. We have compared the ability of
      drugs to induce chewing and retching or emesis in squirrel monkeys; such studies
      are not possible in rodents, which do not vomit. Acute administration of
      oxotremorine (3.3-33 micrograms/kg IM), SKF38393 (1-30 mg/kg SC) or ipecacuanha
      (0.5-0.75 mg/kg PO) caused dose-related increases in purposeless chewing which
      was frequently associated with retching and emesis. Treatment with haloperidol
      (0.015-0.06 mg/kg IM) did not induce chewing. Rather, haloperidol decreased
      spontaneous chewing at doses of 0.03 and 0.06 mg/kg. Our findings indicate that
      at least some drug-induced oral behaviours in rodents may reflect nausea rather
      than dyskinesia.

PMID- 1979180
TI  - Increased sensitivity to benzodiazepine antagonists in rats following chronic
      treatment with a low dose of diazepam.
AB  - The effects of benzodiazepine (BZ) antagonists on operant behavior were examined
      in rats chronically administered a low dose of diazepam (DZ). The low maintenance
      dose of DZ (5 mg/kg twice daily) was selected as more closely associated with its
      anxiolytic effects than the higher treatment doses previously used to study BZ
      dependence. Food-restricted rats were trained to press a lever for food
      reinforcement under a FR20 schedule of reinforcement prior to the start of DZ
      administration. Acute administration of DZ caused a dose-dependent reduction of
      response rates, with 5 mg/kg causing a 50% decrease. Rats treated chronically
      with DZ became tolerant to its rate-suppressant effects as shown by a 5-fold
      increase in the dose of DZ required to reduce FR20 response rates by 50%. The BZ
      antagonist flumazenil (formerly Ro 15-1788; 10-56 mg/kg) suppressed rates of
      responding in rats treated chronically with DZ. The suppression of operant
      responding was obtained when flumazenil was given up to 3 h, but not 18 h, after
      the last treatment with DZ. In contrast, only the highest dose of flumazenil (56
      mg/kg) caused reductions of operant responding when given to rats treated with
      saline. The BZ antagonist CGS 8216 (3.3-33 mg/kg IP), given 10 min prior to the
      session, was similarly more potent and effective at suppressing operant
      responding in rats treated chronically with DZ than saline. This procedure may
      provide a model for the clinical problem of physical dependence to chronically
      administered low, anxiolytic doses of BZ tranquilizers.

PMID- 1979182
TI  - [The role of the serum interleukin-2 inhibitor in the rejection of allogeneic
      hematopoietic tissue in sublethally irradiated mice].
AB  - The influence of ionizing radiation (5 Gy) on the interleukin-2 inhibitor in
      mouse serum has been investigated. It has been shown that the concentration of IL
      2 inhibitor decreases on days 3-6 and increases considerably on days 10-15 after
      irradiation. A correlation has been found between the number of T-helpers in
      spleens of exposed allogenic chimeras and low IL-2 inhibitor content of serum. An
      attempt has been made to use the increased IL-2 inhibitor level for improving the
      acceptance of allogenic cells in the sublethally exposed mice.

PMID- 1979181
TI  - Benzodiazepine concentrations in brain directly reflect receptor occupancy:
      studies of diazepam, lorazepam, and oxazepam.
AB  - Groups of male CF-1 mice received 3 and 10 mumol/kg diazepam, lorazepam, and
      oxazepam intravenously. Between 1 min and 24 h after injection, benzodiazepine
      concentrations were determined by gas chromatography (GLC) in plasma and in one
      brain hemisphere; in the other hemisphere, ex vivo benzodiazepine receptor
      occupancy was measured using 3H-flunitrazepam displacement. Based on GLC data,
      diazepam entered brain rapidly, and was also cleared rapidly, yielding
      desmethyldiazepam and oxazepam as metabolites in plasma and brain. However,
      lorazepam and oxazepam entered brain slowly, with brain:plasma equilibrium
      achieved at 30-60 min; thereafter, the drugs were eliminated from plasma and
      brain in parallel. The time course and extent of ex vivo occupancy were highly
      consistent with GLC data (for diazepam, GLC levels were expressed as the sum of
      diazepam, desmethyldiazepam, and oxazepam, with metabolite concentrations,
      normalized for molecular weight and for in vitro benzodiazepine receptor
      affinity.) Between-method correlations were 0.95 or higher. Thus benzodiazepine
      receptor occupancy is highly dependent on benzodiazepine concentrations in brain.
      Differences in the time-course of onset and duration of pharmacologic activity
      between the highly lipophilic benzodiazepine diazepam and the less lipophilic
      hydroxylated derivatives lorazepam and oxazepam are largely explained by
      differences in systemic kinetics and in the rate of uptake into brain.

PMID- 1979184
TI  - [High energy electrons. Proceedings of the International Congress of Physics and
      Oncologic Radiotherapy. 30 November-1 December 1990].

PMID- 1979185
TI  - [Churg-Strauss allergic granulomatous angiitis. Apropos of 3 cases].
AB  - The authors report three cases of allergic granulomatous angiitis of Churg
      Strauss. They review the different problems posed by this vasculitis: its
      enigmatic relationship with polyarteritis nodosa, its pathophysiology which
      remains a controversial subject and the possible role of immunotherapy with
      allergic extracts. In one of these cases, treatment with steroids associated with
      cyclophosphamide led to a prolonged remission of ten years raising the
      possibility of a cure.

PMID- 1979183
TI  - [Pharmacologic correction of postradiation changes of pain sensitivity in rats].
AB  - With radiation injury caused by superlethal doses of 150 Gy the analgesic effect
      of narcotic drugs decreases and the level of drug analgesia depends on the
      initial status of nociceptive reactions. The role of mu-opiate mechanisms in the
      development of postirradiation analgesia to thermal stimuli has been determined.

PMID- 1979186
TI  - [Zollinger-Ellison syndrome: current therapeutic trends].

PMID- 1979187
TI  - [Surgical treatment of cryptorchism in scrotal hypoplasia].
AB  - In the submitted paper the authors give an account of their experience with the
      treatment of a patient with severe scrotal hypoplasia which is a very rare inborn
      defect. In a group of 1403 boys operated in the last ten years on account of
      cryptorchism this anomaly recorded only once, i.e. in 0.071%. The authors
      recommend a two-stage operation. In the first stage they use a V-Y plastic
      operation to create a neoscrotum. In the second stage orchidopexy is performed.
      Collaboration with a child endocrinologist is important. The aim of
      endocrinological examination is not only evidence of the presence and function of
      the gonads by a hormonal test, but in case of associated anomalies, also the
      assessment of genetic, genital and gonadal sex.

PMID- 1979188
TI  - [The effectiveness of plasmapheresis in treating long-term nonhealing
      gastroduodenal ulcers].
AB  - Plasmapheresis followed by reinfusion of unfrozen autologous plasma favours the
      healing of previously non-healing gastroduodenal ulcers refractory to the
      treatment with histamine H2-blockers. Comparative analysis of the use of
      plasmapheresis in patients with torpid and common relapses has shown that ulcer
      healing supervenes within the same time that is significantly shorter as compared
      to the time of gastroduodenal ulcer healing in the patients' group receiving
      medicamentous treatment alone.

PMID- 1979189
TI  - [The autotransplantation of hematopoietic stem cells from the peripheral blood].
AB  - The authors discuss the existence of polypotent hemopoietic stem cells in the
      peripheral blood as well as a possibility of restoring hemopoiesis by means of
      the given cells after the lethal myelotoxic exposure. In 5 patients with
      hemoblastoses, suspension of mononuclear leukocytes in an amount of 0.5 X 10(9)
      per kg bw was obtained using short-interval leukocytapheresis on blood cell
      separator. After carrying out different schemes of pretransplantation preparation
      the defrosted suspension of mononuclear cells was injected without wash out to
      the patients' central vein. The recovery of the peripheral blood indicators was
      attained on days 10-30 after the autotransplantation of stem blood cells.

PMID- 1979190
TI  - The interrelationship between P-glycoprotein and glutathionyl S-conjugate
      transporter(s)

PMID- 1979191
TI  - High resistance to experimental infection with Fasciola gigantica in Javanese
      thin-tailed sheep.
AB  - Innate resistance of Javanese thin-tailed sheep to Fasciola gigantica was
      investigated in animals infected with single doses of 150 or 500 metacercariae
      and killed 4, 8, 12 or 16 weeks after infection. Infected and non-infected sheep
      had similar values for packed cell volume, mean corpuscular volume, mean
      corpuscular haemoglobin concentration, serum glutamate dehydrogenase, serum gamma
      glutamyl transferase and serum aspartate transferase throughout the trial, except
      for one animal infected with 500 metacercariae from which the highest recovery of
      flukes (55) was made. This animal developed pathologically altered values from 12
      weeks post infection, coincident with the period of greatest hepatic haemorrhage
      and destruction of hepatic tissue by migrating flukes and their entry into bile
      ducts. However, values were altered much less than those reported in other sheep
      given as few as 200 metacercaria of F. gigantica. Both susceptibility to
      infection with F. gigantica, as indicated by percentage take of metacercariae and
      the severity of pathological changes were low in this study in comparison with
      reports involving other breeds of sheep infected with this parasite. These
      findings support the conclusion that Javanese thin-tailed sheep have a high
      innate resistance to F. gigantica.

PMID- 1979192
TI  - [Long-term pain therapy in malignancies using epidural administration of
      opiates].
AB  - The authors explain basic anatomical and pharmacological principles of epidural
      opiate analgesia. As to clinical aspects, the authors mention briefly the
      technique of epidural analgesia. They summarize, based on their own experience
      and data in the literature, the period of insertion of an epidural catheter,
      opiate dosage in morphine equivalents, the need of adjuvant treatment and
      complications. They mention briefly various techniques which can be used in
      epidural opiate analgesia with an outline on perspectives of this method.

PMID- 1979193
TI  - [Guanylate cyclase from human platelets in pulmonary tuberculosis].
AB  - Activity of soluble guanylate cyclase and activating effect of sodium
      nitroprusside were studied in thrombocytes of patients with infiltrative form of
      pulmonary tuberculosis before treatment (as soon as patients entered the
      hospital) and within various periods of the antibacterial therapy course: during
      the first month, 1.5-2, 2.5-3.5 and more than 4 months of treatment. Before
      treatment activity of guanylate cyclase in the patients thrombocytes was similar
      to that of donors independently on severity of the process in lungs (impairment
      of more or less two lung segments). During the antibacterial therapy the enzyme
      activation was detected, which reached 160% of the normal level within 2 months
      course and decreased down to the control rate within 4 months of treatment. The
      activating effect of sodium nitroprusside was distinctly decreased (by 70%) in
      thrombocytes of patients with infiltrative form of pulmonary tuberculosis before
      the treatment course, while the pattern was restored to the normal level,
      comparable with control values in donors, within 4 months of the treatment. The
      stimulating effect of sodium nitroprusside on guanylate cyclase activity in
      thrombocytes of patients with infiltrative form of pulmonary tuberculosis may be
      used as an additional criterion for evaluation of the therapeutic course
      efficiency.

PMID- 1979194
TI  - [Soluble guanylate cyclase from rat platelets during experimental myocardial
      ischemia].
AB  - Activity of soluble guanylate cyclase and regulation of the enzyme were studied
      in thrombocytes of intact rats and under conditions of acute myocardial ischemia
      caused by ligation of left coronary artery. Distinct decrease in the enzymatic
      activity was detected already within 15 min after the operation: down to 19% and
      46%, in presence of Mg2+ and Mn2+, respectively, as compared with control values.
      Within 24 hrs of the ischemia the guanylate cyclase activity was slightly
      increased up to 33.5% in Mg2(+)-containing mixture and was unaltered (46%) in
      presence of Mn2+. Considerable activation of the enzyme by 2.10(-4) M
      dithiotreitol (from 288% to 790%, respectively) was observed after 15 min of
      myocardial ischemia with subsequent normalization (down to 340%) within 24 hrs.
      The data obtained suggest elevation of free-radical reactions, specific for
      myocardial ischemia, as well as high sensitivity of guanylate cyclase in
      thrombocytes to these reactions beginning from the early steps of the disease.
      Absence of the sodium nitroprusside stimulating effect on rat thrombocyte
      guanylate cyclase, found under conditions of both normal state and myocardial
      ischemia, may be due to initial hemdeficiency of the enzyme.

PMID- 1979195
TI  - [Specific monoclonal antibodies to F41 adhesin of enterotoxigenic Escherichia
      coli and their potential uses as diagnostic and therapeutic reagents].
AB  - A set of hybridoma cell lines, namely, L10, B10, C32, B1, E7, E40 and B49,
      secreting monoclonal antibodies (MABs) specific to F41 adhesin antigens of ETEC
      was obtained by somatic hybridization. These MABs manifested strongly specific
      binding reactivities in DA, ELISA and IFA to all tested F41+ ETEC strains. All
      these MABs recognized the same or closely related epitopes on the adhesin, as
      indicated in antigen-competition ELISA with HRP-labeled MABs. The distribution
      patterns of these epitopes which appeared repeatedly on each pilus were
      visualized by MAB-immunogold technique and immunoelectron microscopy. The
      adhesion of ETEC bearing F41 adhesin to the epithelial cells of small intestine
      from new borne calves and piglets was inhibited in vitro by F41-specific MABs. A
      dot-immunobinding assay based on F41-specific MABs was developed for determining
      F41 antigens in fecal samples with HRP-labeled MABs. The assay was highly
      sensitive and specific, and could be used in rapid detection and screening of F41
      adhesin antigens in field samples.

PMID- 1979196
TI  - [Therapy of functional dyspepsia].

PMID- 1979197
TI  - [A voltametric study of the role of the noradrenaline innervation of the
      hippocampus in cats in paradoxical sleep].
AB  - By the method of cyclic voltammetry with carbon fibrous electrodes the signal of
      0.1 V was recorded from the dorsal hippocampus of male cats during natural sleep.
      Systemic injection of 50 mg of L-DOPA and 2.5 mg of isadrin did not influence the
      0.1 V signal but the pyrroxan in a dose of 15 mg caused an increase of the signal
      amplitude. Parallel record of the EEG, myogram, oculogram and voltammogram showed
      that the 0.1 V signal, reflecting the level of alpha-adrenoreceptor
      norepinephrine content in the hippocampus increased in the first and last 1-2
      minutes of the paradoxical sleep phase and was not stably recorded in the slow
      wave phase and the middle part of the paradoxical phase of sleep. The conclusion
      is made that paradoxical sleep of cats consists of three parts. Initial and the
      final parts proceed against the background of the activity of the hippocampus
      alpha-adrenoreceptor norepinephrine innervation, triggering and stopping the
      basal phase of the paradoxical sleep, presumably activated by the serotonin
      innervation. On the basis of the present and previous studies the theory is
      suggested about the trigger function of the hippocampus and of the monoamines,
      innervating it, in the central mechanisms of conditioned behaviour and
      paradoxical sleep.

PMID- 1979198
TI  - [The inhibition of dopamine D1 and D2 receptors in human putamen by antipsychotic
      drugs].
AB  - The inhibition of 3H-SCH 23390 (D1), 3H-spiperone (D2), and 3H-YM-09151 (D2)
      binding to human putamen membranes by four antipsychotic drugs was studied. Two
      substituted benzamides, (-)-sulpiride and YM-09151, weakly inhibited specific 3H
      SCH 23390 binding to D1 receptor sites. The inhibition of 3H-SCH 23390 binding by
      haloperidol and chlorpromazine was also weak in the 10(-8)-10(-6) M range. All
      four drugs potently inhibited 3H-spiperone binding, with the following rank order
      of potency: haloperidol greater than YM-09151 greater than (-)-sulpiride greater
      than chlorpromazine. 3H-YM-09151 binding was potently displaced by YM-09151 (10(
      9) M) and weakly displaced by (-)-sulpiride (10(-7) M). The potency of inhibition
      by haloperidol and chlorpromazine was in the 10(-8) M order.

PMID- 1979199
TI  - [Individual human personality characteristics as a factor in the etiology of
      postvaccinal reactions].
AB  - Healthy volunteers with quite opposite emotional properties defined by means of
      Cattell Personality Questionnaires were shown to have essential differences in
      their postvaccinal reactions. These differences were seemingly caused by
      psychoemotional tension developing in unstable persons as a result of their
      perception of vaccination as a threatening factor. The administration of
      Phenasepam (3 mg) decreased such emotional tension and thus removed negative
      reactions at the postvaccinal period. The preparation had no influence on the
      production of protective antibodies to all types of antigens used for
      immunization.

PMID- 1979200
TI  - Multi-determinate regulation of neuronal survival: neuropeptides, excitatory
      amino acids and bioelectric activity.
AB  - Neuronal survival of dorsal root ganglion-spinal cord cultures was determined
      after treatment with vasoactive intestinal peptide (VIP) and an antagonist to the
      N-methyl-D-aspartate receptor (NMDA). Blockade of NMDA receptors with 2-amino 5
      phosphonovaleric acid (AP5) produced a biphasic response on neuronal survival:
      low concentrations (0.1 microM) resulting in greater survival and higher
      concentrations (100 microM) causing cell death. VIP, a substance with
      demonstrated neurotrophic properties in vitro, prevented the neuronal cell death
      associated with high concentrations of AP5, while having no additive effect on
      the survival-promoting action of low levels of AP5. Electrophysiological studies
      indicated that AP5, although reducing high frequency bursting activity, did not
      significantly reduce the abundant on-going asynchronous activity present in these
      cultures of high density neuronal networks. These data indicate that excitatory
      amino acids have more than one action that can influence neuronal survival during
      development and that VIP can increase neuronal survival in bioelectrically active
      cultures when NMDA channels are blocked. Together with previous studies, these
      data suggest that multiple neurochemical inputs serve to determine the survival
      of spinal cord neurons during development, perhaps through one final common
      pathway: intracellular calcium regulation.

PMID- 1979201
TI  - Sprouting by isolated Helisoma neurons: enhancement by glutamate.
AB  - We tested glutamate for its ability to modulate neurite outgrowth from isolated
      neurons of the adult snail, Helisoma trivolvis. Although glutamate did not induce
      neurite outgrowth from neurons maintained in defined medium, nevertheless it
      showed a dose-dependent ability to enhance the activity of conditioned medium. We
      concluded that glutamate can enhance the release and/or activity of CNS derived
      sprouting factor(s) present in conditioned medium. The general conclusion to be
      drawn from this study is that the ability of a neurotrophic factor(s) to promote
      neurite outgrowth can be regulated by a neurotransmitter. This mechanism may be
      important in the regulation of trophic factors in the adult nervous system.

PMID- 1979202
TI  - Effects of NMDA antagonists on developmental plasticity in kitten visual cortex.
AB  - The existence of Hebb synapses in the visual cortex of young kittens has long
      been postulated. A mechanism for the correlation of activity in simultaneously
      active pre- and postsynaptic neurons could be provided by the properties of the N
      methyl-D-aspartate (NMDA) receptor and its associated Ca2+ channel, which opens
      in a transmitter- and voltage-dependent manner. We have studied the effects on
      cortical plasticity of blocking NMDA receptors in different ways with competitive
      and non-competitive NMDA antagonists. In our first approach, the non-competitive
      NMDA antagonist ketamine, a short-acting dissociative anaesthetic, was injected
      systemically after each of a series of brief monocular exposures. This procedure
      prevented the development of an ocular dominance shift towards the experienced
      eye in the visual cortex. Other short-acting anaesthetics, such as xylazine or
      methohexital, while providing the same depth of anaesthesia, did not have the
      same effect on ocular dominance plasticity. We conclude, therefore, that ketamine
      quite specifically interferes with synaptic consolidation in the visual cortex.
      In order to establish a role of NMDA receptors for cortical plasticity directly
      in the visual cortex, we performed another series of experiments: 2-amino-5
      phosphono-valerate (APV), a competitive NMDA antagonist, was infused
      intracortically by means of implanted osmotic minipumps in kittens, which were
      monocularly deprived for 1-2 weeks. Within a radius of 4-5 mm, the expected
      ocular dominance shift was prevented or reduced. In addition, however,
      physiologically determined cell density and responsiveness to visual stimuli were
      grossly abnormal around the infusion site, and histological cell density was also
      reduced. Similar effects were found when MK801 (a non-competitive NMDA
      antagonist) was used in the same type of experiment. The outcome of both
      experimental approaches makes it very likely that NMDA antagonists somehow
      interfere with cortical plasticity. Their mode of action, however, remains
      ambiguous. Although it is quite possible that blocking of the NMDA channel
      prevents the Hebbian correlative process necessary for synaptic consolidation,
      more complex effects, such as an interference with a neurotrophic action normally
      exerted via the NMDA receptor, may have to be taken into account as well.

PMID- 1979203
TI  - Low serum transglutaminase in patients with intestinal lymphoma and alpha-chain
      disease.

PMID- 1979204
TI  - Predicting the progression to AIDS.

PMID- 1979205
TI  - Predicting progression to AIDS: combined usefulness of CD4 lymphocyte counts and
      p24 antigenemia.
AB  - PURPOSE: To investigate the combined usefulness of CD4 lymphocyte counts and
      human immunodeficiency virus type 1 (HIV-1) p24 antigen in predicting progression
      to the acquired immunodeficiency syndrome (AIDS). PATIENTS AND METHODS: CD4
      lymphocyte counts and HIV-1 p24 antigen status were evaluated over a 4-year
      period in 518 HIV-1-seropositive men enrolled in the Multicenter AIDS Cohort
      Study in Chicago. RESULTS: Twenty-six percent (134 of 518) of the HIV-1
      seropositive cohort had detectable p24 antigen during the study period. Men with
      p24 antigenemia experienced a more rapid decline in CD4 lymphocyte counts than
      men who were persistently p24 antigen-negative (p less than 0.01). Mean CD4
      lymphocyte counts at first detection of p24 antigen were 406 and 455 cells/microL
      for men with incident and prevalent antigenemia, respectively. Antigen was
      detected in 61% (63 of 103) of the men who progressed to AIDS and in only 17% (71
      of 415) of the men who did not (p less than 0.0001). The 4-year estimated
      cumulative AIDS incidence was 86%, 63%, and 21% for men with entry CD4 counts
      less than 200, 200 to 399, and 400 or more cells/microL, respectively. Presence
      of p24 antigenemia was strongly associated with more rapid disease progression
      within each of these CD4 groupings (p less than 0.0001). CONCLUSION: Our data
      indicate that p24 antigenemia can first be detected with moderate CD4 cell
      depletion, is associated with a more rapid decline in the CD4 lymphocyte
      population, and combined with CD4 lymphocyte counts is useful in identifying
      individuals at significantly greater risk of disease progression. Our findings
      provide important information for assessing HIV-1 disease prognosis over a 4-year
      period.

PMID- 1979206
TI  - Cigarette smoking, adiposity, non-insulin-dependent diabetes, and coronary heart
      disease in Japanese-American men.
AB  - PURPOSE: Coronary heart disease has been described to be increased with both
      glucose intolerance and cigarette smoking. All three of these have also been
      reported to be associated with central adiposity (disproportionate deposition of
      fat on the trunk compared to the extremities). The purpose of this analysis was
      to determine the relationship of cigarette smoking to glucose intolerance and
      coronary heart disease, the relationship of cigarette smoking to risk factors
      such as adiposity, body fat distribution, and plasma lipoprotein and insulin
      levels, the relationship of cigarette smoking to these risk factors independent
      of disease status, and whether these risk factors could account for any of the
      relationship between cigarette smoking and disease status. PATIENTS AND METHODS:
      The study design was cross-sectional. The study sample contained 219 middle-aged
      and elderly Japanese-American men: 77 with normal and 74 with impaired glucose
      tolerance and 68 with type II diabetes. There were 54 men with coronary heart
      disease. A detailed smoking history was obtained. Glucose tolerance status was
      established by medical history and a 75-g oral glucose tolerance test. Coronary
      heart disease was determined by medical history and a resting electrocardiogram.
      Adiposity and fat distribution measurements were body mass index (kg/m2),
      skinfold thicknesses, body circumferences, and cross-sectional fat areas by
      computed tomography. Levels of insulin, C-peptide, cholesterol (total, low
      density lipoprotein [LDL], high-density lipoprotein [HDL], HDL2, HDL3, very-low
      density lipoprotein [VLDL]), and triglyceride (total, VLDL) were measured in
      fasting blood specimens. RESULTS: A central pattern of body fat was associated
      with both non-insulin-dependent diabetes mellitus and coronary heart disease.
      Smoking history was related to both adiposity and body fat distribution, and was
      strongly related to coronary heart disease but not to diabetes. Past smokers who
      had smoked up to a month ago were the heaviest while present smokers who were
      currently smoking or had smoked within the past month were the leanest. However,
      although present smokers had reduced amounts of fat, this was attributable to
      those present smokers without heart disease. Present smokers with heart disease
      were not as lean and had increased amounts of intra-abdominal fat. Past smokers
      had the greatest amount of central fat and this was attributable to those with
      heart disease. By two-way (smoking history and coronary heart disease status)
      analysis of covariance, smoking history was significantly related only to
      subcutaneous fat disposition on the chest and abdomen independent of coronary
      heart disease, while coronary heart disease status was strongly related to plasma
      levels of insulin C-peptide, VLDL, HDL, HDL2, and HDL3 cholesterol, and total and
      VLDL triglyceride, independent of smoking history. Further analysis showed that
      none of the body fat variables could account for the risk of coronary heart
      disease associated with smoking history. Higher fasting plasma C-peptide levels
      in past smokers accounted statistically for part of the risk of coronary heart
      disease associated with cigarette smoking. However, this effect was not mediated
      by any of the body fat measurements. CONCLUSIONS: Disproportionately increased
      intra-abdominal fat is related to coronary heart disease but not to smoking
      history. Smoking history is related to coronary heart disease but not to
      diabetes. Weight gain is associated with smoking cessation and appears to be
      concentrated in the central subcutaneous regions, especially for those who have
      coronary heart disease. Weight gain associated with cessation of smoking appears
      to be unrelated to atherogenic changes in lipids, lipoproteins, or insulin. Other
      pathogenic processes must be considered in the association between smoking and
      coronary heart disease.

PMID- 1979207
TI  - Absence of central effects with levocabastine eye drops.
AB  - Twelve healthy volunteers were randomly allocated to receiving in a double-blind
      cross-over fashion levocabastine eye drops (0.5 mg/ml solution) and placebo. They
      were advised to instill 2 drops per eye, four times daily. Each treatment was
      administered for a period of 1 week. Before and after each treatment period
      psychomotor function was assessed using Critical Flicker Fusion Test and the
      Choice Reaction Time Test. At the same time intervals a subjective evaluation of
      sedation was given using a Visual Analogue of Sedation. Both objective and
      subjective measurements showed that no significant treatment effects could be
      detected. It is concluded that repeated instillations of levocabastine eye drops
      are devoid of any sedative side effects.

PMID- 1979208
TI  - 'Overdose' of vecuronium.

PMID- 1979210
TI  - Pulmonary epithelial growth and repair. The fifth Transatlantic Airway
      Conference. January 1990, Lucerne, Switzerland. Proceedings.

PMID- 1979211
TI  - The Neuropharmacology of Serotonin. A conference. New York City, July 10-13,
      1989. Proceedings.

PMID- 1979209
TI  - The intracardiac neurones of the fetal human heart in culture.
AB  - Dissociated cell culture preparations were employed to study intracardiac
      neurones of the atria from human fetal hearts at 9 to 21 weeks' gestation.
      Intracardiac neurones were not observed in cultures dissociated from the
      ventricles. Single neurones, as well as groups, could be identified by phase
      contrast microscopy in all of the atrial cultures prepared from 14 to 21 weeks'
      gestation, and protein gene product 9.5-like immunoreactive neurones were
      detected in cultures from as early as 10 weeks' gestation. The neurones were
      mononucleate, with a prominent nucleolus or multiple nucleoli, and often had
      extensive neurites. Neurones tended to be bigger in cultures from later stages in
      gestation, and these cells appeared to be more mature with a complex pattern of
      neurite outgrowth. Many neurones from 15 to 20 weeks' gestation expressed
      somatostatin-like immunoreactivity in culture. A very low proportion of cultured
      neurones was immunoreactive for neuropeptide Y and its C-terminal flanking
      peptide. Neuropeptide Y-like immunoreactive neurones also contained 5-hydroxy
      tryptamine-like immunoreactivity in culture, but dopamine beta-hydroxylase-like
      immunoreactive neurones were not detected. This study is the first description of
      human intracardiac neurones in culture and forms the essential baseline for
      further direct investigation of these cells.

PMID- 1979212
TI  - Plasticity of fetal and adult CNS serotonergic neurons: role of growth-regulatory
      factors.

PMID- 1979213
TI  - MDMA: historical perspectives.

PMID- 1979214
TI  - Structure-activity relationships of MDMA and related compounds: a new class of
      psychoactive drugs?

PMID- 1979215
TI  - Receptor pharmacology of MDMA and related hallucinogens.
AB  - The data presented herein appear to strongly implicate the brain 5HT2 receptor as
      the site-of-action of the hallucinogenic PIAs and LSD. If so, this discovery
      represents a major step in understanding the molecular pharmacology of
      hallucinogenic drugs. Using radioactive hallucinogenic drugs, detailed properties
      of brain 5HT2 receptors indicating the interaction of 5HT2 receptors with GTP
      binding proteins have been revealed. Autoradiographic studies have revealed an
      extensive cortical distribution of brain 5HT2 receptors; these studies have also
      suggested that the PIAs may be 5HT1C agonists. Radiolabeling studies in
      conjunction with drug discrimination studies indicate that MDMA is apparently
      "amphetamine-like" and not "LSD-like" while MDA is apparently both "LSD-like" and
      "amphetamine-like." However, MDMA does appear to possess the potential to act as
      a 5HT2 agonist at high dosages.

PMID- 1979216
TI  - Neurotoxicity of MDMA and related compounds: anatomic studies.
AB  - The cytotoxic effects of amphetamine derivatives were studied by
      immunocytochemistry to identify the cellular compartments affected by these
      drugs, to obtain morphologic evidence of neuronal degeneration, and to assess the
      potential for regeneration. The substituted amphetamines, MDA, MDMA, PCA, and
      fenfluramine, all release serotonin and cause acute depletion of 5-HT from most
      axon terminals in forebrain. (1) Unequivocal signs of axon degeneration were seen
      at 36-48 hour survivals: 5-HT axons exhibited increased caliber, huge, swollen
      varicosities, fragmentation, and dilated proximal axon stumps. (2) Fine 5-HT axon
      terminals were persistently lost after drug administration, while beaded axons
      and raphe cell bodies were spared. These two types of 5-HT axons, which arise
      from separate raphe nuclei and form distinct ascending projections, are
      differentially vulnerable to psychotropic drugs. (3) From 2-8 months after
      treatment, there was progressive serotonergic re-innervation of neocortex along a
      fronto-occipital gradient. Longitudinal 5-HT axons grew into layers I and VI from
      rostral to caudal, before sprouting into middle cortical layers; this bilaminar
      pattern of growth simulates perinatal development of 5-HT innervation. This study
      demonstrates differential vulnerability of 5-HT projections, evidence for axonal
      degeneration, and sprouting of 5-HT axons leading to re-innervation of forebrain.
      While the sprouting axons are anatomically similar to the type that was damaged,
      it is not known whether a normal pattern of innervation is re-established.

PMID- 1979217
TI  - Neurotoxicity of MDMA: neurochemical effects.

PMID- 1979218
TI  - Neurotoxic effect of MDMA on brain serotonin neurons: evidence from neurochemical
      and radioligand binding studies.
AB  - In summary, the data from both neurochemical and neuroanatomical studies
      demonstrate widespread and long-lasting degeneration of serotonin neurons in
      brain without any major or consistent effects on catecholamine neurons following
      in vivo administration of MDMA in both rats and rhesus monkeys. A detailed
      examination of the parameters involved in the neurotoxic and neurodegenerative
      effects of MDMA on brain serotonin neurons indicate that the severity of the
      lesion is dependent on the dose of drug administered with the drug being more
      potent in rhesus monkeys than in rats. Furthermore, the neurodegenerative effects
      of the drug are long-lasting (up to one year) with respect to neuronal
      regeneration (i.e. recovery of serotonin uptake sites) while functional recovery
      may be permanently impaired since serotonin content remains markedly (40-50%)
      below levels in age-matched controls for as long as one year after drug
      administration. The neurochemical and autoradiographic data suggest that there
      are some regional differences and morphological specificity to the
      neurodegenerative effects of MDMA as demonstrated by greater reductions in
      serotonin uptake sites in brain regions containing primarily terminals while
      regions containing axons of passage and cell bodies are relatively unaffected.

PMID- 1979219
TI  - Synaptic transmission in human neocortex removed for treatment of intractable
      epilepsy in children.
AB  - Synaptic transmission to pyramidal cells was studied in slices of neocortex
      resected from infants and children (n = 10, age 8 months to 13 years) undergoing
      surgical treatment for intractable epilepsy. Most specimens were from the least
      abnormal area of the resection. Stable intracellular recordings could be obtained
      for up to 8 hours. Most of the recorded neurons had electrophysiological
      characteristics similar to those of regular-firing pyramidal cells and were in
      layers III to V, which was confirmed by intracellular staining with Lucifer
      yellow. Local extracellular stimulation evoked a sequence of excitatory and
      inhibitory postsynaptic potentials. After application of the gamma-aminobutyric
      acid antagonist, bicuculline (10-30 microM), extracellular stimulation induced
      large excitatory postsynaptic potentials and epileptiform bursts. Spontaneous
      bursts occasionally occurred in bicuculline. This effect of bicuculline was
      observed in all the tissue samples, even those from infant patients (n = 4, age 8
      16 months). Kynurenic acid depressed or abolished both spontaneous and
      stimulation-induced bursts. The competitive antagonist for N-methyl-D-aspartate
      receptors, DL-2-amino-5-phosphonopentanoic acid decreased the duration of
      bicuculline-induced bursts. These data provide evidence that, similar to rat and
      cat neocortex, excitatory and inhibitory amino acids are important transmitters
      to pyramidal cells in immature human neocortex.

PMID- 1979220
TI  - Hypoglycemia alters striatal amino acid efflux in perinatal rats: an in vivo
      microdialysis study.
AB  - In adult brain, during insulin-induced hypoglycemia, striatal extracellular fluid
      concentrations of the excitatory amino acids glutamate and aspartate rise
      markedly (fourfold to tenfold). In this study, we used in vivo microdialysis to
      determine if insulin-induced hypoglycemia altered striatal amino acid efflux in
      similar fashion in the immature brain. Microdialysis probes were inserted into
      the right striatum of rats on postnatal day 7. After a 2-hour recovery period, in
      each animal a 30-minute baseline sample was obtained. Then insulin (0.6 mu/kg,
      intraperitoneal injection) was administered (n = 6) and dialysate sampling was
      continued over the next 210 minutes (terminal blood glucose level less than 5
      mg/dl). Untreated control rats (n = 6) were sampled over the same time interval.
      After pre-column derivatization with o-phthaldialdehyde, dialysate samples were
      assayed by high-pressure liquid chromatography with electrochemical detection to
      measure their amino acid content; eight amino acids (glutamate, aspartate,
      taurine, glutamine, alanine, serine, glycine, and asparagine) were consistently
      detected. In controls, amino acid efflux did not change over 4 hours. In
      hypoglycemic animals, glutamate efflux increased (peak: 238 +/- 85% of baseline,
      p = 0.02, repeated measures analysis of variance [ANOVA]), glutamine efflux
      declined (to 44 +/- 5% of baseline, p = 0.002, ANOVA), and taurine efflux
      increased (up to 310 +/- 120% of baseline; p less than 0.06, ANOVA). In contrast
      with 9- to 12-fold increases in aspartate efflux reported in adult striatum,
      aspartate efflux increased only slightly (to 174 +/- 69% of baseline; not
      significant).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1979221
TI  - Stereotactic biopsy of an active multiple sclerosis lesion. Immunocytochemical
      analysis and neuropathologic correlation with magnetic resonance imaging.
AB  - Stereotactic biopsy of an active multiple sclerosis lesion in a 23-year-old
      patient with unilateral symptoms and an isolated high-signal-intensity magnetic
      resonance abnormality yielded 10 serial tissue cores (1.0 x 0.5 cm) spanning 40
      mm within and around the lesion. We performed semiquantitative analysis of
      lymphocyte phenotype, using antisera to CD3, CD4, CD8, and CD22 molecules, in 11
      separate perivascular cuffs in three tissue sections from the lesion edge. Total
      cells in the cuffs varied from 10 to 100; ratios of CD4+/CD8+ cells in individual
      cuffs varied from 1.3 to 4.7. Although intense parenchymal infiltrates bordered
      the least cellular cuffs, parenchymal and perivascular cell phenotypes were
      indistinguishable, arguing against selective trafficking of lymphocytes into
      tissue. Individual microfoci of cells displaying CD45RA, CD25, and TQ1 antigens
      were present. The remarkable phenotypic heterogeneity of T lymphocytes in the
      multiple sclerosis lesion border is consistent with exposure in situ to a
      diversity of differentiating stimuli. Histologic demyelination correlated very
      closely with the signal-intensity abnormality observed on magnetic resonance
      imaging. These studies provide unusual insight into the histologic and
      immunocytochemical morphologic appearance of the active multiple sclerosis
      plaque.

PMID- 1979222
TI  - Process analysis in behavioral family therapy.
AB  - Process research in behavioral family therapy (BFT) is a hitherto neglected area
      with the notable exception of the work of Alexander and Patterson with their
      colleagues. However, the development of instruments to assess therapist's
      behavior during the treatment session seems timely for the following reasons: (a)
      to investigate the relationship between therapist behavior and outcome, (b) to
      improve therapist training/supervision, (c) to establish treatment integrity in
      comparative outcome studies, and (d) to monitor treatment progress. For these
      purposes two sets of instruments were developed: (a) a category system to
      describe the content of a session, which is rated every 30 seconds and (b)
      several rating scales to evaluate therapist behavior, including relationship
      competency, ability to structure a session, didactic competence, ability to
      initiate behavioral probes, use of appropriate intervention strategies, use of
      reinforcement, and dealing with uncooperativeness. Scales are described, and data
      on their reliability and utility are presented.

PMID- 1979223
TI  - Rural health: a challenge for medical education. Proceedings of the 1990
      invitational symposium. San Antonio, Texas, February 1-3, 1990. Proceedings.

PMID- 1979224
TI  - Immunopathological analysis of interstitial renal lesions in elderly people.
AB  - The incidence of focal lymphoid infiltrates in the renal interstitium was
      examined in autopsy cases of young and old subjects, and the infiltrating
      lymphocytes were immunohistologically characterized by a panel of monoclonal
      antibodies. Histologically, 198 and 227 autopsy cases over 60 years of age
      (87.2%) were shown to have mononuclear cell infiltrates of varying degree in the
      renal interstitium, whether or not these were accompanied by progressive
      arteriosclerotic changes. Above all, severely infiltrating foci in the renal
      interstitium were frequently found in the elderly over 70 years of age
      overlapping arterio-artherolosclerotic changes. In contrast, in the 54 younger
      control subjects under 49 years of age, the incidence of such a lesion was less
      (5.6%). An immunohistologic study revealed that the infiltrating mononuclear
      cells were predominantly composed of CD4+ cells, whereas CD22+ B cells were
      apparently lesser in number. Moreover, a considerable proportion of T cells was
      activated as judged by IL-2 receptor expression. From these findings, we now
      propose that susceptibility to the development of interstitial renal lesions in
      the elderly involves the cellular immune response, and may be related to an age
      associated disturbance in regulatory T-cell function.

PMID- 1979225
TI  - The effect of HIV-1 infection on the lipid fatty acid content in the membrane of
      cultured lymphocytes.
AB  - Elevations in the levels of unsaturated fatty acids (FAs) in membrane lipids lead
      to an increase in cell membrane fluidity and may also be involved in cell fusion
      and death through the loss of normal membrane function and integrity. Since the
      infection of susceptible cells with HIV leads to cell fusion and subsequent loss
      of viability, the present study was undertaken to see whether HIV infection can
      alter the relative content of unsaturated FAs in the host cell membrane and to
      determine whether this change correlates with cell death. Peripheral lymphocytes
      (PBLs) of a healthy donor and two CD4+ cell lines were chosen: MT-4, which is
      killed following HIV infection, with significant cell death being observed 5 days
      postinfection, and H9 which is not killed. Measurements of FA content of the two
      cell lines and PBLs, either before or at 6, 24, and 48 h after infection, showed
      a significant rise in the concentration of unsaturated FAs followed by a drop in
      the concentration of saturated FAs in the MT-4 cell line. With regard to the H9
      cell line similar results were obtained at 6 h from infection. However, at 24 and
      48 h the concentrations of saturated FAs returned to preinfection levels while
      the concentrations of unsaturated FAs dropped to levels even lower than those
      obtained at zero time. No significant changes in FA composition were found with
      PBLs.

PMID- 1979226
TI  - AIDS following mother-to-child transmission of HIV-2.
AB  - Mother-to-child infection with HIV-2 is thought to be rare, and there have been
      few previous reports of transmission by this route. Reports of morbidity
      associated with HIV-2 infection in children are also rare. We describe eight
      children born to mothers who were infected with HIV-2; five developed AIDS, and
      three were still seropositive at 17-49 months of age. The only apparent route of
      HIV-2 transmission was from mother to child, except for one child who had been
      transfused. Three of the children with AIDS died, all having decreased CD4+
      lymphocytes and mitogen responses. Further studies are needed to determine the
      prevalence and natural history of mother-to-child transmission of HIV-2.

PMID- 1979227
TI  - Protein import into mitochondria and peroxisomes.

PMID- 1979228
TI  - Excitatory amino acid receptor agonists stimulate membrane inositol phospholipid
      hydrolysis and increase cytoplasmic free Ca2+ in primary cultures of retinal
      neurons.
AB  - A variety of neurotransmitters are believed to elicit effects through receptor
      stimulated inositol phospholipid metabolism. It appears that most major types of
      retinal neurons receive a direct glutamatergic input. The aim of the present
      studies was to characterize excitatory amino acid (EAA) receptor-mediated
      breakdown of inositol phospholipids and changes in Ca2+ homeostasis in primary
      avian retinal cell cultures. Cell monolayers, prepared from 8-day-old chick
      embryo neural retina, were labelled with [3H]inositol for 48 h, and used after 7
      days in vitro. Kainic acid stimulated the accumulation of inositol phosphates in
      a time- and dose-dependent manner (ED50 = 30 microM). The EAA receptor agonists
      glutamate, N-methyl-D-aspartate (NMDA), ibotenate and quisqualate were all
      active, with the rank order: glutamate greater than kainate greater than NMDA
      much greater than ibotenate approximately quisqualate. External Ca2+ was required
      for these effects. Agonist actions were inhibited by type-specific antagonists,
      and also Mg2+ in the case of glutamate and NMDA. Glutamate, NMDA and kainate also
      elevated cytosolic free Ca2+ in individual retinal cells loaded with the Ca2(+)
      sensitive dye Fura-2, as assessed by digital fluorescence ratio imaging
      microscopy. The agonist-induced increases in [Ca2+]i were largely dependent on
      extracellular Ca2+, independent of membrane depolarization and were blocked by
      Mg2+ for glutamate and NMDA. These results demonstrate that vertebrate retinal
      cells possess EAA receptors coupled to intracellular signal transduction
      pathways.

PMID- 1979229
TI  - Wheat-germ agglutinin mimics metabolic effects of insulin without increasing
      receptor autophosphorylation.
AB  - Expression of insulin metabolic effects can be obtained by anti-receptor
      antibodies without activation of the tyrosine kinase activity [O'Brien R. M.,
      Soos M. A. and Siddle K. (1987) EMBO J. 6, 4003-4010; Forsayeth J. R., Caro J.
      F., Sinha M. K., Maddux B. A. and Goldfine I. D. (1987) Proc. natn. Acad. Sci.
      U.S.A. 84, 34,448-34,514; Ponzio G., Contreres J. O., Debant A., Baron V.,
      Gautier N., Dolais-Kitabgi J. and Rossi B. (1988) EMBO J. 7, 4111-4117; Hawley D.
      M., Maddux B. A., Patel R. G., Wong K. Y., Mamula P. W., Firestone G. L.,
      Brunetti A., Verspohl E. and Goldfine I. D. (1989) J. biol. Chem. 264, 2438-2444;
      Soos M. A., O'Brien R. M., Brindle N. P. J., Stigter J. M., Okamoto A. K.,
      Whittaker J. and Siddle K. (1989) Proc. natn. Acad. Sci. U.S.A. 86, 5217-5221.].
      Recently, we have proposed that receptor cross-linking is sufficient in itself to
      stimulate glycogen synthesis, even if aggregation was performed on receptors
      mutated on Tyr 1162 and Tyr 1163 and thus devoid of tyrosine kinase activity
      [Debant A., Ponzio G., Clauser E., Contreres J. O. and Rossi B. (1989)
      Biochemistry 28, 14-17]. The aim of this study was to gain information on the
      involvement of receptor clustering in the expression of the different insulin
      biological effects. To this end, we studied the mimetic effects of wheat-germ
      agglutinin, which is likely to induce receptor aggregation without interacting
      with the receptor protein moiety. Wheat-germ agglutinin failed to promote DNA
      synthesis, whereas the lectin behaved as a potent mimicker of insulin on tyrosine
      aminotransferase activity and amino-acid transport. However, this stimulatory
      effect did not parallel the activation of receptor autophosphorylation. Our data
      reinforce the idea that the expression of the metabolic effects of insulin are
      not strictly dependent on a general tyrosine kinase activation.

PMID- 1979230
TI  - Stereoselective effect of warfarin and bilirubin on the binding of 5-(o
      chlorophenyl)-1,3-dihydro-3-methyl-7-nitro-2H-1,4-benzodiazepin-2- one
      enantiomers to human serum albumin.
AB  - The binding of the title benzodiazepine enantiomers and its modulation by
      warfarin and bilirubin were studied by chromatography on human serum albumin
      (HSA) immobilized on Sepharose 4B, and also by a combination of ultrafiltration
      and circular dichroism (UF-CD) methods. In the absence of warfarin and bilirubin
      the binding of the benzodiazepine was not stereoselective. (S)-Benzodiazepine and
      (S)-warfarin mutually increased the binding of each other, while the binding of
      (R)-benzodiazepine was preferentially enhanced on HSA saturated with bilirubin.

PMID- 1979232
TI  - Abstracts of the V Biennial Winter Workshop on Schizophrenia. Badgastein,
      Austria, January 28 to February 3, 1990.

PMID- 1979233
TI  - Anti TSH-receptor antibodies in pregnant patients with autoimmune thyroid
      disorder.
AB  - The study was designed to test further the usefulness of the radioreceptor assay
      of thyroid stimulating hormone (TSH) binding inhibitory immunoglobulins (TBII)
      and the bioassay of thyroid stimulating antibodies (TSAb) or TSH stimulated cAMP
      response inhibitory antibodies (TBkAb) in the prediction of neonatal thyroid
      dysfunction. Of 63 pregnant women with a current or past history of autoimmune
      thyroid disorder, 11 (one with active and six with a past history of Graves'
      disease and four with autoimmune thyroiditis) gave birth to a baby with transient
      hyper or hypo-thyroidism. Only high maternal titres (which could persist after
      partial thyroidectomy) of anti TSH-receptor antibodies (TRAb) led to neonatal
      hyperthyroidism. Both types of assay were able to detect the antibodies
      responsible for transitory neonatal autoimmune thyroid disease. TBII values
      reflected TSAb titres so that there was a significant correlation between the
      results of both assays in women with Graves' disease and in neonatal sera.
      Positive TBII and TBkAb activities were present in 5 of the 28 women with
      autoimmune thyroiditis. Therefore, when TBII is positive, the functional
      characterization of the antibodies warrants the use of the bioassay.

PMID- 1979231
TI  - [Collagenous colitis: a disease difficult to define].
AB  - The Authors report a case with watery chronic diarrhoea not related to
      malabsorption or to inflammatory bowel disease or to intestinal neoplasm. Colonic
      biopsy, performed during colonoscopy, with the histologic finding of collagenous
      material in the subepithelial space associated to epithelial alterations and to
      the presence of inflammatory cells, confirmed the diagnosis of this rare
      pathologic condition. The pathogenesis of the syndrome, however, is still
      unknown.

PMID- 1979234
TI  - Ca2+ role on the effect of phorbol esters on the spontaneous quantal release of
      neurotransmitter at the mouse neuromuscular junction.
AB  - The effect of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) on the
      release process was studied in presence of different extracellular Ca2+
      concentrations, in the mouse phrenic-diaphragm preparation. Hemidiaphragms were
      incubated for 2 h at room temperature in the presence or absence of TPA. TPA
      increased the basal frequency of miniature end plate potentials (mepp's) in a
      dose-dependent manner, resulting in a maximal increase of 280% at a concentration
      of 0.5 microM. An inverse relationship between extracellular Ca2+ concentration
      and TPA effect was observed: at high extracellular concentrations of Ca2+ the
      action of TPA decreased significatively, while at low Ca2+ concentrations the
      effect of TPA was remarkably augmented. The highest effect of TPA was obtained
      when tested in a calcium-free medium. TPA also increased mepp frequency
      stimulated by 10 mM K+. As at basal conditions, the effect of TPA was higher at
      lower concentrations of extracellular calcium. The results suggest that the
      effect of stimulation of PKC on neurotransmitter release at the mice
      neuromuscular junction is not exerted at the level of calcium influx to the nerve
      terminal. Moreover the action of calcium and TPA seems to be superimposed. The
      effect of K+ on neurotransmitter release could be explained not only by
      depolarization of the nerve terminal but by increasing the pool of activable PKC.

PMID- 1979235
TI  - Double-label analyses of somatostatin's coexistence with enkephalin and gamma
      aminobutyric acid in amacrine cells of the chicken retina.
AB  - Double-label analyses were performed to investigate somatostatin's coexistence
      with either enkephalin or gamma-aminobutyric acid (GABA) in amacrine cells of the
      chicken retina. Double-label immunocytochemistry revealed that although some
      amacrine cells labelled only for somatostatin or enkephalin, approx. 81% and 85%
      of somatostatin-immunopositive cells in the center and periphery of the retina,
      respectively, were also enkephalin-immunoreactive. Somatostatin
      immunocytochemistry combined with autoradiography of high-affinity [3H]GABA
      uptake revealed that approx. 18% of somatostatin-immunoreactive amacrine cells
      exhibit high-affinity uptake of [3H]GABA.

PMID- 1979236
TI  - Region-selective stress-induced increase of glutamate uptake and release in rat
      forebrain.
AB  - The study describes stress-induced changes in high-affinity uptake and release of
      glutamate by synaptosomal preparations from several regions of rat brain. The
      results demonstrate that restraint stress can lead to increased glutamate uptake
      and release in limbic forebrain regions (frontal cortex, hippocampus and septum)
      but not in the striatum. The increase in glutamate uptake was evident after 30
      min of stress. A plateau (140-150% of unhandled controls) was reached after 1 h
      and was maintained after 4 h of continuous stress. The stress-induced increase in
      glutamate uptake was observed with glutamate concentrations of up to 10 microM,
      but not with 500 microM. the results indicate that forebrain glutamatergic
      terminals are activated by stressful stimuli in a regionally selective manner,
      and suggest that enhanced high-affinity uptake is important in clearing increased
      levels of released glutamate.

PMID- 1979237
TI  - Possible role of dopamine D1 receptor in the behavioural supersensitivity to
      dopamine agonists induced by chronic treatment with antidepressants.
AB  - The effect of chronic treatment with antidepressants (ADs) on the behavioral
      responses to LY 171555, a selective D2 receptor agonist, SKF 38393, a selective
      D1 receptor agonist, and B-HT 920, a selective DA autoreceptor agonist, was
      studied in rats. In normal rats small, intermediate and high doses of LY 171555
      produced hypomotility, hyperactivity and stereotypies, respectively. Chronic but
      not acute pretreatment with imipramine (IMI) greatly potentiated the motor
      stimulant effect of LY 171555, but failed to modify its stereotypic and sedative
      effect. The potentiation of the motor stimulant effect of LY 171555 was observed
      also after chronic, but not acute, treatment with desmethylimipramine (DMI),
      mianserin (MIA) or repeated electroconvulsive shock (ECS). Chronic treatment with
      IMI failed to modify the effect of SKF 38393 (motor stimulation, grooming and
      penile erection), but reversed the sedative effect of B-HT 920 into a motor
      stimulant response. The motor stimulant response to LY 171555 in IMI-pretreated
      animals was suppressed by L-sulpiride, a D2 antagonist, and by a combination of
      reserpine with alpha-methyltyrosine (alpha-MT), but it was only partially
      antagonized by high doses of SCH 23390, a selective D1 antagonist. The results
      indicate that chronic treatment with ADs potentiates the behavioural responses
      mediated by the stimulation of postsynaptic D2 receptors in the mesolimbic system
      and suggest that this behavioural supersensitivity is due to enhanced
      neurotransmission at the D1 receptor level.

PMID- 1979238
TI  - Alpha 1-adrenergic receptors in the brain: characterization in astrocytic glial
      cultures and comparison with neuronal cultures.
AB  - Binding of [125I]HEAT to membranes prepared from primary cultures of astrocytic
      glial cells was time-dependent and 70-85% specific. Various adrenergic agonists
      and antagonists competed for [125I]HEAT binding according to the potencies of
      prazosin greater than, yohimbine greater than or equal to, clonidine,
      norepinephrine (NE), and propranolol. Scatchard analysis showed the Bmax of 209
      fmol/mg protein and a Kd of 184 pM for [125I]HEAT binding by astrocytic glial
      membranes. Pretreatment of astrocytes with NE resulted in a dose-dependent
      downregulation of [125I]HEAT binding sites with a maximal response observed after
      8 h at 100 microM NE. Removal of NE from cultures after pretreatment resulted in
      a time- and protein synthesis-dependent recovery of binding sites to control
      levels within 120 h. Incubation of astrocytic glial cultures with NE stimulated
      phosphoinositide (PI) hydrolysis in a time- and dose-dependent manner with a
      maximal stimulation of 2-fold observed in 60 min by 100 microM NE. Clonidine
      expressed differential effects on alpha 1-adrenergic receptors of the neuronal
      and astrocytic glial cultures. Pretreatment with 10 microM clonidine caused a 40%
      decrease in the Bmax of [125I]HEAT binding without influencing the Kd value in
      neuronal cultures. This downregulatory effect of clonidine was associated with a
      reduction in the ability of NE to stimulate PI hydrolysis in clonidine pretreated
      cells. In contrast to neuronal cultures, clonidine neither downregulated
      [125I]HEAT binding sites nor stimulated PI hydrolysis in glial cultures.

PMID- 1979239
TI  - Insulin co-injection suppresses the thermogenic response to glutamate
      microinjection into the VMH in rats.
AB  - Selective stimulation of ventromedial hypothalamic nucleus (VMH) neurons by
      microinjection of the excitatory amino acid glutamate sharply increased
      interscapular brown adipose tissue (IBAT) and core temperatures in urethane
      anaesthetized rats. This effect was blocked by co-injection of insulin (0.1-1
      microgram) though not an inactive insulin analog, TNB3 insulin. Injection of
      insulin (1 microgram) into the contralateral VMH or systemic administration of
      insulin (1 microgram) had no effect on the thermogenic response to intra-VMH
      glutamate. These results complement those showing that intra-VMH insulin
      suppresses the basal firing rate of sympathetic nerves to IBAT and diminishes
      cold-induced nonshivering thermogenesis in BAT and add support to the view that
      insulin functions as an inhibitory signal on VMH neurons controlling
      thermogenesis in BAT.

PMID- 1979240
TI  - Gangliosides prevent MPTP toxicity in mice--an immunocytochemical study.
AB  - The role of gangliosides in preventing neuronal degeneration was examined in a 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse parkinsonian
      model. Intraventricular injections of a ganglioside mixture prior to MPTP
      treatment reduced MPTP's toxicity on tyrosine hydroxylase-positive neurons in the
      substantia nigra. This raises the interesting possibility that early ganglioside
      administration may be beneficial in the treatment of neurodegenerative disorders.

PMID- 1979242
TI  - Sports-medicine considerations of lesser metatarsalgia.
AB  - In this article I have attempted to discuss some of the injuries seen in the
      lesser metatarsals of athletes. Athletic injuries in many cases do not differ
      greatly from those seen in the nonathletic population. The diagnosis, prevention,
      and treatment of athletic injuries might parallel the same injuries seen in the
      general population. I have tried to extend my experience to the reader. Like any
      practitioner, my treatment is colored by many factors. I try to assess every
      athletic injury by what I call the eight "Ses" of sports medicine. Shoe gear,
      stretching, strength, sport, surface, speed, style, and support. Each of these
      categories is examined for its relationship to cause and prevention of the
      injury. In many cases, a simple change in the athletic shoe gear can eliminate a
      problem. The same is true for the style of play or running form. The importance
      of strength and flexibility in the athlete cannot be overemphasized. The surface
      on which and speed at which an event is played can influence injury rates and
      methods of prevention. The sport is often the sole cause for certain injuries.
      Most of all, from a podiatric standpoint, the structure or biomechanics of the
      injury must be assessed. It is from this viewpoint that we as podiatrists can
      make the largest contribution in sports medicine. We are uniquely qualified by
      our training to spot and correct injuries due to mechanical overload and failure
      of foot mechanics. No other specialty has the background in performing
      biomechanically sound surgery. Simple and straightforward podiatric techniques
      are often successful in prevention and treatment of sports injuries.

PMID- 1979241
TI  - Prophylactic treatment of grass pollen-induced asthma with cetirizine.
AB  - In a double-blind randomized parallel-group study, six investigators enrolled 43
      subjects to study the prophylactic effect of 10 mg cetirizine b.i.d. on grass
      pollen-induced asthma. The control group received 60 mg b.i.d. terfenadine, given
      to avoid withdrawals from the trial because of hay fever symptoms. Subjects were
      included in the study between the appearance of the first symptoms of hay fever
      and those of pollen-induced asthma. The hay fever and asthma symptoms, visual
      analogue scores (VAS), FEV1 and self-assessment data on complaints, salvage
      treatment and peak-flow values were statistically analysed. Both treatments were
      well tolerated, with a low and similar incidence of side-effects. During the last
      3 weeks of treatment, six (32%) of the 19 subjects on cetirizine who were
      evaluable for efficacy remained free of asthma complaints, and another two (10%)
      had only a single minor attack. None had a grade 3 (incapacitating) attack.
      Conversely, only one (5%) of the 20 evaluable subjects on terfenadine remained
      complaint free, and all others (95%) had multiple attacks, which incapacitated
      three (15%) of them. Nasal obstruction, dyspnoea, morning peak flow, consumption
      of beta 2-mimetics and an efficacy index on asthma, combining complaints and
      rescue drug consumption, were significantly better on cetirizine (P less than
      0.05). It is concluded that cetirizine is able to prevent the exacerbation of
      asthma induced by grass pollen.

PMID- 1979243
TI  - Puncture wounds and foreign body reactions.
AB  - Puncture wounds present a clinical dilemma when considering the amount of
      intervention. Through a logical and thorough history and physical examination a
      wound score is reached. This scoring system allows for a more objective approach
      to treatment. Although by no means perfect, wound score will help the clinician
      in decision making for this difficult clinical problem. Guidelines for the total
      score are as follows: 1. If the total score is between 1 and 4, treatment is
      local cleansing and observation. 2. If the total score is between 5 and 8, local
      cleansing, incision and drainage, and exploration for foreign body is performed
      with placement of drain. Oral antibiotic regimen is up to local standards of
      care. 3. If the total score is 9 or more, incision and drainage are mandatory,
      and wound lavage, intravenous antibiotics, hospitalization, and immobilization
      are indicated.

PMID- 1979244
TI  - Assignment of an erbB-like DNA sequence to linkage group VI in fishes of the
      genus Xiphophorus (Poeciliidae).
AB  - The inheritance of 23 protein polymorphisms was compared with the inheritance of
      a DNA restriction fragment length polymorphism (RFLP) of a strongly cross
      hybridizing erbB-related sequence, epidermal growth factor receptor-like-1
      (EGFRL1), in Xiphophorus clemenciae X X. milleri-derived backcross hybrids. Two
      polymorphic bands were noted in this cross with a v-erbB probe after PstI
      digestion: a 10-kilobase (kb) band in X. clemenciae and a 9-kb band in X.
      milleri. Joint segregation analysis of the RFLPs and protein polymorphisms
      indicate that this erbB-related sequence can be assigned to Xiphophorus linkage
      group VI, which also comprises genes coding for glutamine synthetase (GLNS),
      nucleoside phosphorylase-2 (NP2), and transferin (TF). We have designated this
      RFLP as alleles at a locus called EGFRL1 because of very strong cross
      hybridization with the v-erbB probe, known to be homologous to the mammalian EGFR
      gene. This mapping assignment is the first autosomal linkage of an oncogene
      sequence reported in fish, which provide a large number of genetically controlled
      experimental tumor models.

PMID- 1979245
TI  - Modulation of drug sensitivity by dipyridamole in multidrug resistant tumor cells
      in vitro.
AB  - The concept of overcoming multidrug resistance using modulators is based on the
      hypothesis that there will be a synergistic interaction between the modulator and
      the cytotoxic agent. We examined the ability of dipyridamole (DPM) to
      synergistically enhance drug sensitivity in drug-sensitive KB-3-1 cells and their
      drug-resistant variants, KB-GRC1 and KBV1 cells, using median effect analysis to
      produce a quantitative measure of the extent of synergy. The drug-resistant
      variants were resistant to vinblastine (VBL), colchicine (COL), and etoposide (VP
      16) in the order VBL greater than COL greater than VP-16 on the basis of 50%
      inhibitory concentration values obtained by clonogenic assay with continuous drug
      exposure. The extent of staining with the monoclonal antibody HYB-241, directed
      at a Mr 180,000 form of the mdrI gene product, correlated with drug resistance
      for all three drugs (r greater than or equal to 0.92). DPM and verapamil elevated
      the steady state content (Css) of VBL, but there was no correlation between
      elevation of Css and the extent of synergy observed. DPM enhanced the
      cytotoxicity of VBL and COL in a synergistic manner in KB-GRC1 cells, and in KBV1
      cells DPM interacted synergistically with VBL. VPL was synergistic with VBL only
      in KB-GRC1 cells. No synergy was observed in the parental KB-3-1 line. These data
      indicate that, although both DPM and verapamil can increase Css in cells not
      expressing P-glycoprotein, such an increase was not associated with synergy. In
      cells expressing mdrl, synergy was observed, and it was greatest for the
      cytotoxic agent for which expression of mdrl produced the greatest fold
      resistance and enhancement of Css. However, neither the level of resistance, the
      level of expression of mdrl, nor the ability of the modulator to alter Css
      accurately predicted whether the interaction would be truly synergistic. We
      conclude that additional factors determine the nature of the drug interaction.

PMID- 1979246
TI  - Differentiation-dependent expression of I and sialyl I antigens in the developing
      lung of human embryos and in lung cancers.
AB  - The localization of two carbohydrate antigens, I and sialyl I antigens, in the
      lungs of developing human embryos was investigated using specific monoclonal
      antibodies and compared with the distribution patterns of the known embryonic
      antigen, stage-specific embryonic antigen-1 (Lex hapten). When the future bronchi
      were actively developing from the bronchial buds in the lungs of 50- to 53-day
      old embryos, the immature bronchial bud cells were I-, Lex+, while the fully
      differentiated epithelial cells of the larger bronchus were I+, Lex-. When the
      bronchiolar bud cells matured into bronchiolar epithelial cells in the lung of a
      12-week-old embryo, the immature bronchiolar bud cells were I-,Lex+, while the
      fully differentiated epithelial cells of the bronchioles were I+,Lex-. Sialylated
      forms of the antigens finally appeared in the lungs of 18-week-old embryos, when
      the terminal bud cells actively proliferated and underwent the differentiation
      process into epithelial cells of alveoli and alveolar ducts. The immature
      terminal bud cells at this stage were I-, sialyl I-, Lex+, sialyl Lex-i+, while
      the fully differentiated alveolar epithelial cells were I+, sialyl I+, Lex-,
      sialyl Lex-i-. After 8 months, the flattened mature alveolar epithelial cells
      were strongly positive for both I and sialyl I antigens, the strong expression of
      which continued after birth and even into the adult stage. These distribution
      patterns indicate that the I and sialyl I antigens are specific markers for the
      differentiated type cells in each stage of development, while Lex and related
      embryonic antigens were specific to the immature bud cells in every stage. The
      above-described differentiation-dependent expression patterns of these antigens
      seem to be reflected in the distribution of these antigens in human lung cancers,
      i.e., I and sialyl I antigens were expressed in lung cancer cells more weakly
      than in normal lung cells, while the Lex and sialyl Lex-i were expressed in
      cancer cells much more strongly than in normal lung cells. This was further
      reflected in the serum levels of these antigens in the patients with respiratory
      disorders. The distribution pattern of the serum levels of these antigens in
      patients with lung cancers showed sialyl Lex-i greater than sialyl I, indicating
      that these serum antigens originated from the lung cancer lesion where sialyl Lex
      i is much more dominant than sialyl I antigen.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1979247
TI  - In vivo selection of human tumor cells resistant to monoclonal antibody-Vinca
      alkaloid immunoconjugates.
AB  - UCLA-P3 human lung adenocarcinoma cells were grown in nude mice and given
      repetitive treatments of a monoclonal antibody-Vinca alkaloid immunoconjugate.
      Although this therapy resulted in a greater than 4-fold reduction in mean tumor
      mass of the established tumors, some animals experienced a reinitiation of tumor
      growth after cessation of conjugate treatment. Two such animals were treated
      again with high doses of monoclonal antibody-Vinca but one of the tumors was no
      longer regressed by the drug conjugate. The tumor was excised, enzymatically
      dissociated, and grown in tissue culture. Cultured cells were reimplanted in nude
      mice and subjected to further therapy with a monoclonal antibody-Vinca conjugate.
      The resulting tumors were also refractory to the immunoconjugate therapy. This
      cycle was repeated for a total of three times and resulted in the serial in vivo
      selection of three conjugate resistant variants. The mechanism responsible for
      the in vivo resistance of human tumor cells to the monoclonal antibody-Vinca
      immunoconjugate is unknown but does not appear to involve antigen modulation,
      altered tumor cell growth rate, or an apparent decrease in tumor targeting in
      vivo. The resistance was also not accompanied by any detectable elevation in
      multidrug resistance 1 mRNA or P-glycoprotein expression. Significantly, the
      resistance pattern was observed only in vivo and was not maintained by cells
      grown in vitro.

PMID- 1979248
TI  - A Ki-1 (CD30)-positive T (E+, CD4+, Ia+)-cell line, DL-40, established from
      aggressive large cell lymphoma.
AB  - A new human lymphoma cell line, designated DL-40, was established from the
      peripheral blood of a 64-year-old woman with leukemic conversion of aggressive
      large cell lymphoma. The cell line grew in suspension with or without forming
      clumps of cells and exhibited large, round, or multiple nuclei in the relatively
      abundant cytoplasm that was positive for acid phosphatase. The cells expressed a
      Ki-1 antigen (CD30), E+, CD2+, CD4+, CD45+, Ia+ phenotype and had rearranged T
      cell receptor beta chain but were negative for CD15, HTLV-I, and Epstein-Barr
      virus nuclear antigen. Chromosome analysis of this cell line showed a human
      female karyotype with complex hyperdiploid abnormalities. DL-40 cells produced
      tumors histologically similar to the original lymphoma when transplanted into
      nude mice and immunosuppressed hamsters. The DL-40 cell line could provide a
      useful tool for the understanding of biology of the Ki-1-positive non-Hodgkin's
      lymphoma.

PMID- 1979249
TI  - Cytotoxic effects of dihydroorotase inhibitors upon human CCRF-CEM leukemia.
AB  - 6-L-Thiodihydroorotate (TDHO) and 2-oxo-1,2,3,6-tetrahydropyrimidine-4,6
      dicarboxylate (HDDP) are potent inhibitors of mammalian dihydroorotase in vitro
      (R. I. Christopherson, K. J. Schmalzl, E. Szabados, R. J. Goodridge, M. C.
      Harsanyi, M. E. Sant, E. M. Algar, J. E. Anderson, A. Armstrong, S. C. Sharma, W.
      A. Bubb, and S. D. Lyons, Biochemistry, 28: 463-470, 1989). Using human CCRF-CEM
      leukemia cells growing in culture, TDHO and HDDP as the free acids have 50%
      inhibitory concentration (IC50) values of 32 microM and greater than 1000 microM,
      respectively, whereas for TDHO methyl ester, the IC50 value is 25 microM, and for
      HDDP dimethyl ester, the IC50 value is 21 microM. These IC50 values were not
      affected by addition of dihydroorotate, uridine, or deoxycytidine to the culture
      medium. TDHO methyl ester (25 microM) had only slight inhibitory effects upon the
      dihydroorotase reaction of de novo pyrimidine biosynthesis in growing leukemia
      cells, cells arrested in G2 + M phases of the cell cycle. At 250 microM TDHO
      methyl ester, analysis of cell extracts by high-performance liquid chromatography
      showed that after 4 h carbamyl aspartate had accumulated from undetectable levels
      to 760 microM, whereas UTP decreased from 580 to 110 microM and CTP from 350 to
      86 microM, indicating inhibition of dihydroorotase in growing leukemia cells. IMP
      accumulated from 63 to 350 microM, total guanylates increased while adenylates
      decreased, and the adenylate energy charge decreased from 0.91 to 0.69 after 4 h.
      The cellular concentration of 5-phosphoribosyl 1-pyrophosphate increased from 180
      to 290 microM due to sparing from pyrimidine nucleotide biosynthesis resulting in
      complementary stimulation of the de novo purine pathway. HDDP dimethyl ester at
      concentrations of up to 250 microM had no discernable effect upon pyrimidine or
      purine nucleotide biosynthesis. At 25 microM HDDP-dimethyl ester, cells arrested
      in G2 + M phases initially, with accumulation of cells in G1/G0 at later times.
      These data suggest that the primary mechanisms of growth inhibition for TDHO and
      HDDP involve inhibition of cell cycle progression from late G2 or M phase to G1
      phase and that blockade of the pyrimidine pathway by TDHO is a secondary effect
      found at higher concentrations.

PMID- 1979250
TI  - Differential expression of transglutaminase in human erythroleukemia cells in
      response to retinoic acid.
AB  - Two human erythroleukemia cell lines, HEL and K562, express transglutaminase
      activity. The enzyme was identified as a tissue transglutaminase following
      chromatographic purification. All-trans-retinoic acid (10 microM) stimulated
      differentiation in HEL cells as judged by a 4-fold increase in hemoglobin content
      and a reduction in cell proliferation. The transglutaminase activity increased 9
      fold. This increase in transglutaminase was the result of a pretranslational
      regulation of the gene as revealed by Northern blot analysis of mRNA. These
      changes were not a result of cell apoptosis, since parallel DNA degradation
      catalyzed by a Ca2(+)-dependent endonuclease could not be demonstrated. The K562
      cells, in contrast, showed no transglutaminase induction following exposure to
      retinoic acid and displayed no changes in maturation markers or cell growth.

PMID- 1979251
TI  - Sequential emergence of distinct resistance phenotypes in murine erythroleukemia
      cells under adriamycin selection: decreased anthracycline uptake precedes
      increased P-glycoprotein expression.
AB  - First-step Adriamycin (doxorubicin)-resistant mutants of the murine
      erythroleukemia cell line PC4 were cloned from Adriamycin-containing (10 ng/ml)
      methylcellulose at a frequency of 3 x 10(-4). They demonstrated 1.6- to 2.4-fold
      stable resistance to Adriamycin. Most were cross-resistant to etoposide, but not
      to vincristine, and were without enhanced expression of mdr genes, which code for
      P-glycoproteins. Two different murine erythroleukemia cell lines, PC4 and C7D,
      were passaged in suspension culture into stepwise increasing amounts of
      Adriamycin. No high-level resistant mutants were isolated de novo; cells
      initially displayed low-level resistance to Adriamycin and etoposide. Two
      stepwise doublings of the drug concentration were needed before PC4 cells
      acquired vincristine resistance, but there was no detectable overexpression of
      mdr or a change in anthracycline uptake. In a subsequent doubling of Adriamycin
      concentration, the cells showed a further increase in resistance to all three
      drugs and now a decreased anthracycline accumulation. However, there was still no
      detectable increase in mdr expression as judged by Northern analysis of poly(A)+
      enriched RNA and Western blot analysis of membrane proteins. Only after a fourth
      doubling of Adriamycin concentration did the cells demonstrate enhanced
      expression of mdr and P-glycoprotein. Equivalent mutants of C7D were selected,
      but generally at lower Adriamycin concentrations. Verapamil partially lowered
      resistance, but failed to restore parental susceptibility in any mutant; it
      caused an increased uptake in those mutants showing decreased anthracycline
      accumulation, including those that did not overexpress mdr. This study
      demonstrated different resistance phenotypes among mutants appearing
      spontaneously under stepwise drug selection; mutants with vincristine resistance
      and decreased anthracycline uptake preceded those associated with over-expression
      of P-glycoprotein.

PMID- 1979252
TI  - Relationship of polymorphisms near the rat prolactin, N-ras, and retinoblastoma
      genes with susceptibility to estrogen-induced pituitary tumors.
AB  - Chronic treatment of rats with the synthetic estrogen diethylstilbestrol is known
      to induce the formation of pituitary tumors, and such tumor induction is highly
      dependent on the strain of rat used. We examined three previously discovered
      restriction fragment length polymorphisms in rats to determine whether these
      correlated with susceptibility to tumor formation. The results indicate that the
      presence of particular alleles of the polymorphic N-ras and retinoblastoma (Rb)
      genes does not correlate with tumor susceptibility. A polymorphism upstream of
      the rat prolactin (Prl) gene is due to the presence or absence of an Alu-like
      sequence. Results of this study indicate that animals bearing the allele lacking
      this Alu-like insertion are more likely to develop larger pituitary tumors in
      response to diethylstilbestrol than are animals in which the Prl allele contains
      the insertion. In addition, we show that the N-ras, Rb, and Prl genes are
      dispersed in the rat genome and that the polymorphic alleles of the Prl genes are
      segregating as classical Mendelian alleles. These results suggest that the
      difference in the Prl gene itself or in some closely linked gene is related to
      tumor resistance or susceptibility.

PMID- 1979253
TI  - Expression of ERBB2 in human gastric carcinomas: relationship between p185ERBB2
      expression and the gene amplification.
AB  - The expression of p185ERBB2 in a total of 34 human gastric carcinoma tissues as
      well as in corresponding normal mucosa was examined by Western blotting. More
      than 70% of both tumor tissues and normal mucosa showed p185ERBB2 expression at
      various levels. Eighteen (55%) cases revealed higher levels of p185ERBB2 in the
      tumor than in normal mucosa, while 13 (38%) cases showed lower levels in the
      tumor tissues. Higher expression of p185ERBB2 was frequently observed in well
      differentiated adenocarcinomas, with the incidence between well differentiated
      type and poorly differentiated type being significantly different (P less than
      0.05). Comparative immunohistochemical analysis revealed the consistent results
      with p185ERBB2 expression obtained by Western blotting in well differentiated
      adenocarcinomas. Of the 34 cases, three well differentiated adenocarcinomas had
      extremely high levels of p185ERBB2. ERBB2 gene was amplified in two of the three
      tumors, but the amplification differed by the tumor site from where the sample
      was obtained. Another tumor which showed an extremely high level of p185ERBB2 but
      no gene amplification demonstrated a high level of binding protein to the TATA
      box that is located in the promoter of the ERBB2 gene. A high level of TATA
      binding protein was also detected in gastric carcinoma cell lines which contain a
      single copy of ERBB2 gene and a high expression of p185ERBB2.

PMID- 1979254
TI  - [XbaI polymorphism in intron 22 of factor VIII and gene potential for prenatal
      diagnosis of hemophilia A].
AB  - Polymorphism of an XbaI restriction endonuclease site in intron 22 of the factor
      VIII gene was studied. 79 heredity-unrelated X chromosomes from 83 Chinese were
      analyzed. The frequency of the polymorphic site was 0.56, providing polymorphism
      information content (PIC) of 0.49. Fourteen out of 17 families with hemophilia A
      could be diagnosed by the Xba 1/22i restricted fragment length polymorphism
      (RFLPs). Therefore, as a genetic marker within the factor VIII gene, Xba I/22i
      RFLPs should be useful for prenatal diagnosis of hemophilia A and for detection
      of its carriers.

PMID- 1979255
TI  - The stomach: factors of importance to the anaesthetist.

PMID- 1979256
TI  - Neuromuscular blocking agents used with antibiotics.

PMID- 1979257
TI  - Beta-adrenergic drug therapy in newborn canine endotoxic shock.
AB  - The mortality of septic shock remains high in newborns. Although the
      effectiveness of adrenergic drug therapy continues to be controversial,
      adrenergic drugs have been used for the treatment of newborn endotoxic shock. To
      elucidate the effects of beta-adrenergic drugs on the fulminant hemodynamic
      deterioration of newborn endotoxic shock, newborn dogs (2-10-day-old, 264-800 g)
      were given Escherichia coli lipopolysaccharide (LPS; 10 mg/kg iv) and treated
      with isoproterenol (0.1 micrograms/kg/min) or dopamine (5 micrograms/kg/min)
      infusion from 5 to 120 min after LPS injection. Isoproterenol attenuated the
      effects of LPS by increasing the mean arterial pressure (32 +/- 2 vs. 13 +/- 1
      mmHg at 120 min), cardiac output (183 +/- 29 vs. 118 +/- 23 ml/min/kg at 120
      min), and the survival time (5.3 vs 2.9 hr). However, dopamine did not improve
      the hemodynamic deterioration. As dopamine-beta-hydroxylase activity in the blood
      was significantly lower in newborn dogs than in adult dogs, inadequate response
      of newborn dogs to dopamine was thought to be in part due to enzymatic
      immaturity.

PMID- 1979258
TI  - Glutamine synthetase activity of developing astrocytes is inhibited in vitro by
      very low concentrations of lead.
AB  - This study has dealt with the inhibition by lead of glutamine synthetase (GS)
      activity in homogenates of mixed glial primary cultures, 95% enriched in
      differentiating astrocytes. A 70% inhibition was observed with a lead
      concentration of only 2.5 microM. Prevention of the inhibition by addition of
      EDTA or dithiothreitol is compatible with the conclusion that the effect is
      mediated by binding of lead ion to sulfhydryl moieties of the enzyme. Among
      several other cations tested, only mercury, which has a similarly high binding
      affinity for sulfhydryl moieties, inhibited the enzyme. The inhibitory effect of
      lead was relatively specific, since no inhibition of another astrocytic marker
      enzyme, lactate dehydrogenase, of the oligodendroglial marker enzyme, 2',3'
      cyclic nucleotide 3'-phosphohydrolase, or of the plasma membrane marker, Na,Ka
      ATPase, was observed with concentrations of lead that produced a 70% decrease of
      GS. Because of the critical role of GS in regulation of extracellular glutamate,
      the findings raise the possibility that glutamate-induced neuronal injury is
      involved in the genesis of the cognitive defects associated with chronic low
      level lead exposure in young children.

PMID- 1979259
TI  - The 8th International Congress of Clinical Enzymology. May 30-June 1, 1989,
      Toronto, Canada. Proceedings.

PMID- 1979260
TI  - The effect of non-insulin-dependent diabetes on serum concentrations of tumor
      associated carbohydrate antigens of CA19-9, CA-50, and sialyl SSEA-1 in
      association with the Lewis blood phenotype.
AB  - Serum concentrations of the tumor-associated carbohydrate antigens CA19-9, CA-50,
      and sialyl SSEA-1 were measured in non-insulin-dependent diabetic patients
      without diseases causing the elevation of those antigens, and the relationship to
      diabetic conditions was studied. The patients of the Lewis blood group phenotype
      of Lea (23%) had higher serum CA19-9, CA-50, and sialyl SSEA-1 than those of Leb
      (67%) and Le(-) (10%). Lea patients with high HbA1c (greater than 10%) had
      significantly higher serum CA19-9 and CA-50 than those with low HbA1c (less than
      or equal to 7%). Leb patients with high HbA1c also had elevated CA19-9 and sialyl
      SSEA-1. In Leb patients, diabetic nephropathy was associated with increased CA19
      9 levels. Diabetic retinopathy was also accompanied by high carbohydrate antigens
      in Leb patients, but the difference was not significant. Leb patients treated
      with sulfonylurea or insulin had increased CA19-9 and CA-50. The changes in serum
      concentrations of these carbohydrate antigens might have some relationship not
      only to the Lewis blood phenotype, but also to diabetes.

PMID- 1979261
TI  - Pyridostigmine does not reverse dexamethasone-induced growth hormone inhibition.
AB  - Glucocorticoids inhibit the growth hormone (GH) response to a variety of stimuli,
      including GH-releasing hormone (GHRH) in vivo, but they increase GHRH-stimulated
      GH secretion when added, in vitro, to animal and human pituitary cells. This
      discrepancy has led to the hypothesis that glucocorticoids act in vivo by
      increasing somatostatin secretion from the hypothalamus. To examine this
      hypothesis, we used a cholinergic drug, pyridostigmine (PD), which reduces
      hypothalamic somatostatin secretion. Eight normal volunteers were studied. They
      underwent four tests: (1) GHRH test; (2) Dex + GHRH (GHRH test after treatment
      the night before, with dexamethasone (Dex)); (3) PD + GHRH; (4) Dex + PD + GHRH.
      Dex significantly inhibited the GH response to GHRH expressed as area under the
      GH/time curve (AUC, microgram/1/min) (mean +/- SEM = 895.2 +/- 196.6 vs 1970.9 +/
      600.1, P less than 0.05). PD significantly increased the AUC of GH secretion in
      PD + GHRH compared with GHRH alone (3541.2 +/- 571.3 vs 1970.9 +/- 600.1, P less
      than 0.01) but by no means restored completely the normal GH response to GHRH,
      when given to Dex-pretreated subjects. Furthermore, the mean AUC of Dex + PD +
      GHRH was significantly lower than that of PD + GHRH (1621.7 +/- 500.6 vs 3541.2
      +/- 571.3, P less than 0.01), demonstrating that Dex continues to exert its
      inhibitory effect on GH secretion in the presence of PD. These results suggest
      that glucocorticoid-induced GH inhibition does not act solely through an increase
      in hypothalamic somatostatin secretion.

PMID- 1979262
TI  - Treatment of macroprolactinomas with a new non-ergot, long-acting dopaminergic
      drug, CV 205-502.
AB  - Eleven patients with prolactin-producing pituitary adenomas were treated with the
      new non-ergot, long-acting dopamine agonist, CV 205-502, for a period of 2-18
      months (mean 11 months). Tumour volumes ranged from 1.9 to 64 ml in seven
      patients who were newly diagnosed, and from 0.1 to 3.1 ml in four patients who
      had been treated for macroprolactinomas by oral bromocriptine or depot
      bromocriptine (Parlodel LAR). Plasma prolactin values ranged from 3.5 to 360 U/l
      before institution of CV 205-502 treatment in these 11 patients. The following
      observations were made: (1) plasma prolactin values fell dramatically in all
      patients, and values within the normal range were obtained in five patients at
      once-daily doses of CV 205-502 between 0.075 and 0.300 mg; (2) tumour size
      reduction was obtained in all patients with macroadenomas on pretreatment CT
      scans. Tumour reduction was associated with the development of a partial empty
      sella in five patients, and with visualization of the pituitary in six cases; (3)
      bitemporal hemianopia (five patients) disappeared in four patients and improved
      in one patient. Oculomotor palsy receded in one patient; (4) signs of anterior
      pituitary insufficiency improved or normalized in most cases affected; (5) mild
      nausea or dizziness during the first days of CV 205-502 treatment and/or during
      several days after a dose increase were observed in three patients. We conclude
      that CV 205-502 in a once daily dose is an effective and safe alternative in the
      long-term treatment of macroprolactinomas.

PMID- 1979263
TI  - [Cryptogenetic ulcerative colitis. Our clinical experience with new therapeutic
      approaches].
AB  - Sixteen patients with flare-ups of ulcerative colitis were studied. Before and
      after treatment, patients were submitted to the customary laboratory tests and to
      x-ray (contrast enema) and endoscopic examination, biopsy material being
      harvested during the latter. Treatment consisted in the oral administration of 2
      4 g 5-ASA daily for 30 days. Only one patient did not tolerate 5-ASA which was
      withdrawn. All other patients had good or very good results with remission of
      symptoms.

PMID- 1979264
TI  - Noradrenaline thermogenesis in conscious and anaesthetised pouched mice
      (Saccostomus campestris).
AB  - 1. The metabolic response to injections of noradrenaline (NA) and saline
      (control) was investigated in conscious and anaesthetised (sodium pentobarbitone)
      pouched mice, Saccostomus campestris. 2. NA injection produced a calorigenic
      response which was significantly greater than that elicited by saline injection
      in both conscious and anaesthetised animals. 3. This calorigenic response was
      enhanced by motor activity in conscious pouched mice, but the exclusion of
      measurements recorded during visible activity eliminated the influence of
      movement. 4. Anaesthetised pouched mice underwent mild Hypothermia and displayed
      a retarded metabolic response to NA injection which suggests that anaesthesia
      affects the expression of NA-induced thermogenesis. 5. The validity of proposed
      techniques for the measurement of NA thermogenesis is further discussed.

PMID- 1979265
TI  - Temperature regulation and basal metabolic rate in the spotted skunk, Spilogale
      putorius.
AB  - 1. Metabolic rate, body temperature, and evaporative water loss of six spotted
      skunks were measured at air temperatures between 8 and 40 degrees C. 2. The mean
      metabolic rate of spotted skunks at thermoneutral air temperatures was 30.5%
      below that predicted by body mass. 3. Thermal conductance, body temperature, and
      rates of evaporative water loss were like those of similar sized mammals. 4. The
      non-elongate body form, omnivorous diet, and low level of activity of spotted
      skunks distinguish them from other mustelids and may account for their lower-than
      expected basal metabolism.

PMID- 1979266
TI  - Effects of genetic selection on growth rate and intestinal structure in the
      domestic fowl (Gallus domesticus).
AB  - 1. Pieces of small intestine taken from chickens subjected previously to
      continuous selection, relaxed selection or no selection for rapid growth were
      used to estimate villus surface area and microvillus development to determine
      what effects genetic selection might have on factors controlling intestinal
      function. 2. Crypt size and the rates at which enterocytes migrated out of crypts
      were also measured, after injection of tritiated thymidine, to determine the time
      course of microvillus elongation. 3. Differences in growth rates measured between
      highly selected, relaxed selected or unselected birds were found to be correlated
      with parallel changes in villus surface area. Selection for growth did not change
      the density, dimensions or pattern of development of enterocyte microvilli.
      Microvilli did, however, produce a maximal 20-fold increase in villus surface
      area under all conditions. 4. Crypt size and enterocyte migration rates did not
      vary significantly between tissue taken from unselected and relaxed selected
      chickens. Tissue taken from highly selected birds had a crypt size and enterocyte
      migration rate 40% higher than values found for the other two groups of chickens.
      5. The possibility that early genetic selection increased growth potential by
      uncoupling diet-induced changes on crypt hyperplasia from secondary effects on
      villus structure, and that later selection increased growth potential by
      increasing appetite, is discussed.

PMID- 1979267
TI  - Role of Ca2+ and prostaglandin in regulation of active Na+ transport in frog
      skin.
AB  - 1. The role of prostaglandins and intracellular Ca2+ in regulation of active
      transepithelial sodium transport in frog skin were studied by examinations of
      effects of the calcium ionophore A23187 on short-circuit current (SCC) and
      intracellular voltage. 2. A23187 and arachidonic acid induced a marked increase
      in both SCC and prostaglandin E2 synthesis. 3. In indomethacin treated skins
      A23187 did not stimulate but on the contrary inhibited the basal SCC. 4. The
      A23187-induced increase in SCC was associated with a decrease in the fractional
      resistance of the apical membrane and a depolarization of the cells. 5. In skins
      pretreated with indomethacin, the A23187 induced inhibition of SCC coincided with
      a slight hyperpolarization of the cellular potential and an increase in
      fractional resistance of the apical membrane.

PMID- 1979268
TI  - Activation of glucose transport by activatory receptor agonists of adenylate
      cyclase in rat adipocytes.
AB  - 1. Catecholamine, glucagon, and adrenocorticotropic hormone stimulated 2
      deoxyglucose (2-DG) uptake via an increase in glucose transporters in plasma
      membranes, similarly to insulin. 2. In contrast to the action of insulin, the
      stimulating effects of these agonists on 2-DG uptake were abolished when Gi was
      not activated. 3. The mode of the 2-DG uptake stimulation was partially different
      among these agonists.

PMID- 1979269
TI  - [Carrier detection and gene analysis in a Duchenne muscular dystrophy family].
AB  - Probe C7, pERT87-15, 754 which on the short arm of the X chromosome are used in
      the linkage analysis of a DMD family by the use of restriction fragment length
      porlymorphism (RFLP) and serum CPK, CPK-MB are detected. Three obligated carriers
      are determined and we also find a deletion to pERT87-15 in this family.

PMID- 1979270
TI  - [The ambiguity of the mRNA polyadenylation sites in the human embryonic liver].

PMID- 1979271
TI  - Aneuploidy in Drosophila. III: Aneuploidogens inhibit in vitro assembly of taxol
      purified Drosophila microtubules.
AB  - The in vitro effects of aneuploidogens on taxol-purified microtubules from whole
      Drosophila melanogaster and mouse brain were studied by a spectrophotometric
      assay and electron microscopy. Colchicine, acetonitrile, propionitrile,
      acrylonitrile, dimethylsulfoxide (DMSO), griseofulvin, and cadmium chloride
      inhibit microtubule assembly, whereas methoxyethyl acetate (MEA) does not.
      Qualitatively similar results were observed with D. melanogaster and mouse brain
      microtubules. The in vitro results from D. melanogaster correlate well with
      previously published results from in vivo assays monitoring induced sex
      chromosome aneuploidy in that effective aneuploidogens are observed to affect
      microtubule assembly. The inclusion of taxol does not appear to qualitatively
      affect the assembly assays with the chemicals tested. In contrast with results
      from assembly assays, the tested aneuploidogens, including colchicine, do not
      promote disassembly to taxol-purified microtubules. It is possible that taxol has
      shifted the equilibrium and stabilized the formed microtubules to the extent that
      they are no longer sensitive to aneuploidogen-induced disassembly.

PMID- 1979272
TI  - Time course of the effect of intravenous dimetindene maleate.
AB  - In order to evaluate the time course of its effects, dimetindene maleate has been
      investigated in a histamine provocation model in man. Eight healthy male
      volunteers were treated i.v. with 4 mg dimetindene maleate or sodium chloride
      solution in a double blind, cross over study. Intracutaneous histamine injections
      were given at -1, 2, 5, 14, 17, 20, 23, 26, and 29 h following drug
      administration and the areas of flares and wheals were measured after 5, 10, 20,
      and 30 min. There was strong inhibition of the development both of flares and
      wheals, which was more pronounced for the former. Baseline adjusted areas under
      the curve differed significantly following drug and placebo treatment. The
      maximum effect was observed at 2 h. The mean residence time of the inhibitory
      effect was calculated to be approximately 13 h compared to the mean residence
      time of dimetindene in blood of approximately 5 h, which indicates a non-linear
      relationship between blood level and effect.

PMID- 1979273
TI  - Effects of the 5-HT3 antagonist GR38032F (ondansetron) on benzodiazepine
      withdrawal in rats.
AB  - Effects of the 5-HT3 receptor antagonist GR38032F (ondansetron) on
      chlordiazepoxide withdrawal were assessed in rats which received chlordiazepoxide
      b.i.d. for 21 days at doses up to 40 mg/kg per injection. Withdrawal signs
      recorded were: body weight and food intake, which fell and then recovered over 9
      days. Saline or GR38032F (1.0, 0.1 or 0.01 mg/kg) were administered b.i.d. during
      withdrawal. Clear withdrawal signs were seen in rats treated with saline after
      chronic chlordiazepoxide. However, GR38032F at 0.1 mg/kg reduced the severity of
      withdrawal. At 0.01 mg/kg GR38032F shortened withdrawal duration, but did not
      diminish peak withdrawal signs. At 1.0 mg/kg GR38032F, did not attenuate
      withdrawal signs at all. GR38032F (0.01-1.0 mg/kg) had no effect on ad lib food
      intake, therefore the attenuation of withdrawal was probably not simply due to
      stimulation of appetite. These data support recent claims that GR38032F
      attenuates benzodiazepine withdrawal, and they indicate that this effect shows an
      inverted U-shaped dose-response curve.

PMID- 1979275
TI  - Relaxant effect of benzodiazepines on uterine rings isolated from estrogen
      treated rats.
AB  - K(+)-contracted rat uterine rings were relaxed in a concentration-dependent
      manner by the benzodiazepines Ro 5-4864, diazepam and clonazepam, as well as by
      the putative peripheral benzodiazepine antagonist PK 11195. The relaxation
      induced by diazepam was not counteracted by the central antagonist Ro 15-1788 (10
      microM), and the relaxant effects of Ro 5-4864 and of diazepam were not prevented
      by either the GABAA antagonist bicuculline (10 microM) or the beta-adrenoceptor
      antagonist propranolol (1 microM). The mechanism underlying the relaxant effects
      of benzodiazepines on K(+)-contracted uterine rings is still under study.

PMID- 1979274
TI  - Adenosine A2 stimulation of tyrosine hydroxylase in rat striatal minces is
      reversed by dopamine D2 autoreceptor activation.
AB  - The adenosine agonist, 2-chloroadenosine, stimulated tyrosine hydroxylase
      activity in rat striatal minces; this effect was attenuated by activation of
      dopamine (DA) D2 autoreceptors with N-n-propylnorapomorphine and antagonized by
      theophylline. Forskolin and 8-bromo-cAMP also increased tyrosine hydroxylase
      activity and their effects were not altered by 2-chloroadenosine. D1, alpha, beta
      and 5-HT agonists did not affect tyrosine hydroxylase activity. Evidently, A2
      receptors on DA nerve terminals stimulate striatal DA synthesis and this effect
      is negatively modulated by D2 autoreceptors, probably via changes in
      intracellular cAMP levels.

PMID- 1979276
TI  - Body temperature discriminates between full and partial benzodiazepine receptor
      agonists.
AB  - The benzodiazepine full agonist loprazolam and the beta-carboline ZK 93423
      produced hypothermia in mice (1-30 mg/kg i.p.). Maximal effects were seen at
      relatively low doses of these compounds. In contrast, the partial agonists Ro 17
      1812 (a benzodiazepine) and ZK 91296 (a beta-carboline), did not modify rectal
      temperature at doses up to 30 mg/kg i.p. (which would be receptor saturating).
      Body temperature may therefore be a useful test for discriminating between full
      and partial agonists at the benzodiazepine receptor.

PMID- 1979277
TI  - Spermidine enhancement of [3H]MK-801 binding to the NMDA receptor complex in
      human cortical membranes.
AB  - The effects of spermidine on the binding of [3H]MK-801 to the N-methyl-D
      aspartate (NMDA) receptor complex was studied in human cerebral cortical
      membranes. [3H]MK-801 binding was increased from 56 +/- 5 fmol/mg protein (mean
      +/- S.E.M., n = 7) to 319 +/- 71 fmol/mg protein in the presence of 200 microM
      spermidine. The ED50 for spermidine stimulation of [3H]MK-801 binding was 89 +/-
      22 microM (mean +/- S.E.M., n = 6). In the presence of glutamate (1 microM) plus
      glycine (1 microM) the ED50 was reduced to 5.5 +/- 0.7 microM. The increase in
      binding in the presence of spermidine was characterised by an increase in the
      rate of association of [3H]MK-801. In the presence of spermidine. [3H]MK-801 was
      inhibited by AP5. 7-chlorokynurenic acid and ifenprodil with IC50 values of 0.5
      +/- 0.3 24 +/- 19 and 91 +/- 28 microM, respectively. None of these antagonists
      was a competitive inhibitor of the spermidine stimulation of [3H]MK-801 binding.
      Thus spermidine modulates the NMDA receptor complex in human brain, providing
      further evidence that the complex is similar in rat and human cortex.

PMID- 1979278
TI  - Restriction endonuclease analysis of chromosomal DNA from Listeria monocytogenes
      strains.
AB  - Restriction endonuclease analysis of chromosomal DNA was applied to thirteen
      Listeria monocytogenes strains alongside the more conventional typing methods of
      serotyping and phage typing. The organisms were isolated from cases of sporadic
      listeriosis (nine strains); from an occasional nosocomial cluster (two strains);
      and from food samples (two strains). Purified DNAs were digested with EcoRI
      restriction endonuclease, and restriction fragments separated by electrophoresis.
      Restriction patterns correlated well with phage patterns, but also allowed typing
      of the phage-untypable strains. DNA fingerprinting appears to be a potentially
      helpful tool for epidemiological investigations of listeric infections,
      particularly when phage typing fails to determine the identity or diversity of
      the isolates.

PMID- 1979279
TI  - [The correlation of the serotonin-positive and anxiolytic activities of
      nonbenzodiazepine substances].
AB  - The anxiolytic activity of serotonin agonists (buspirone, ipsapirone, campirone,
      caplapirone, 1-pyrimidinyl-piperazine) determined in rats on 3 experimental
      models of anxiety closely correlates with the degree of inhibition of impulse
      release of 3H-serotonin by electrically stimulated slices of the midbrain raphe
      dorsal nucleus (r = +0.85) but not the slices of the cerebral hemispheric cortex
      (r = +0.60) of the rats. The anxiolytic activity of neuroleptics (chlorpromazine,
      trifluorperazine), antidepressant (amitriptyline, imipramine) and beta-carbolines
      (harmane, 3.4-tetramethyleneharmane) corresponds well (r = +0.94) to the ability
      of the drugs to potentiate the hyperpolarizing effects of serotonin in the rat
      sensory ganglion.

PMID- 1979280
TI  - [Monoamine antagonism in relation to the direct effect of neuroleptics on the
      release of stimulating amino acid neuromediators].
AB  - In the experiments on the superfused synaptosomes of the rat brain cortex it was
      shown that both typical and atypical neuroleptics in the micromolar range of
      concentrations decrease K(+)-stimulated 3H-D-aspartate release. Serotonin (10(-5)
      M) and dopamine (10(-7) M) do not affect D-aspartate release. Serotonin abolishes
      the action of all typical neuroleptics studied (haloperidol, chlorpromazine,
      fluphenazine) and of sulpiride and clozapine, but not of carbidine. Dopamine
      antagonizes only the effect of atypical neuroleptics.

PMID- 1979281
TI  - [The types of central serotonin receptors, their functional role and
      participation in the action of psychopharmacologic agents].
AB  - The review deals with the classification of the central serotoninergic receptors
      based on the data of the radioligand studies. The localization of the receptors
      and the biochemical, electrophysiological and behavioral effects mediated by the
      activation of different types of the central serotoninergic receptors are
      considered. The involvement of the serotoninergic mechanisms of the brain in the
      anxiolytic effect of buspirone and the related compounds are discussed as well as
      in the antipsychotic and antianxiety effects of neuroleptics.

PMID- 1979282
TI  - Fundal height in normal pregnant Nigerian women: anthropometric gravidogram.
AB  - Fundal height measurements in centimeters (FH) have always been an objective
      method of evaluating fetal growth in pregnancy. The popular Mcdonald's rule
      refers mainly to caucasions unfortunately. Since FH may actually vary in an
      anthropological sense it was considered necessary to apply Mcdonald's rule to
      African subjects. Pregnant Nigerian women were studied to observe how their
      fundal height values compared with those obtained for caucasian women in western
      communities. A gravidogram was derived for the 10th, 50th and 90th centiles.
      Values outside the range of 10-90th centiles are to be used for the prediction of
      small-for-dates and large-for-dates babies accordingly. Prediction formulae for
      the various centiles derived from regression analysis were obtained and their
      usefulness in clinical anthropological practice using fundal height measurement
      highlighted. A simple universal formula for African subjects is presented. Normal
      values of pregnant women for somatotype, height, and abdominal girth are also
      presented. The result of this survey demonstrates a significant difference in
      fundal height values of African women from those of the hitherto utilized
      standards derived from the study of caucasian women, especially in early
      pregnancy. This report suggests an early intra-uterine growth retardation in the
      African pregnancies which is corrected in the third trimester.

PMID- 1979283
TI  - Some characteristics of labor in ethnic minorities in Amsterdam.
AB  - A retrospective study of labor in immigrants, subdivided into Blacks, Asians and
      Mediterraneans (Turks and Moroccans) and autochthonous Dutch in Amsterdam over a
      10-year period showed definite differences. The second stage was shortest in
      Blacks and Mediterraneans but they sustained perineal tears and episiotomies less
      frequently. Differences in positions at birth were small except for occipito
      posterior position which was very rare in Asians and Mediaterraneans. The rate of
      cesarean section was highest and that of instrumental vaginal delivery lowest in
      Blacks, and latter being highest in Asians. Retained placenta occurred less often
      in immigrants than in Dutch.

PMID- 1979284
TI  - The relationship between beta-endorphin levels and uterine muscle contractions
      during labor.
AB  - Plasma beta-endorphin (BE) levels (8.6 +/- 0.8 pmol/l) (mean +/- SE) were lower
      in the third trimester than in non-pregnant controls (14.8 +/- 1.1 pmol/l) (P
      less than 0.001), increased during labor, to 29.3 +/- 4.4 pmol/l (P less than
      0.005) and decreased, 72 h after delivery, to 3.5 +/- 0.4 pmol/l (P less than
      0.001). BE levels were found to correlate significantly with uterine muscle
      contraction (r = 0.966, P less than 0.05) and with cervical effacement (r =
      0.974, P less than 0.05) during labor.

PMID- 1979285
TI  - Pregnancy outcome following Wurm's operation: elective versus emergency.
AB  - Wurm's technique for correction of an incompetent os during pregnancy is a
      simple, but not well recognized procedure. In this study, an attempt has been
      made to evaluate this procedure for elective and emergency cases. Pregnancy
      outcome of 142 patients who underwent Wurm's operation at the Nehru Hospital,
      Postgraduate Institute of Medical Education and Research, Chandigarh is
      presented. Twenty pregnancies resulted in abortion, 47 pregnancies terminated
      preterm and 75 pregnancies continued beyond 37 weeks. A total of 119 live births
      yielded a success rate of 83.3%. There were three stillbirths and six infants
      died during the neonatal period resulting in a fetal salvage of 81%. These
      results are comparable to those reported for other procedures.

PMID- 1979286
TI  - Influence of suckling on plasma concentrations of somatostatin, insulin and
      gastrin in lactating women.
AB  - The effects of suckling on plasma somatostatin, insulin and gastrin values were
      evaluated in eight nursing women on the 3rd to 4th day postpartum. Plasma
      prolactin levels were also determined. Prolactin levels increased in response to
      suckling, as expected. Insulin levels also rose, whereas somatostatin and gastrin
      concentrations did not change after suckling. It is possible that the suckling
      induced hyperinsulinemia blunts the somatostatin response to suckling in humans.

PMID- 1979287
TI  - Multiple diagnoses and procedures during hysterectomy.
AB  - Seldom does a gynecologic patient, who needs a hysterectomy, have a single
      diagnosis. Among 2892 gynecologic patients who needed a hysterectomy, only 127
      had a single diagnosis. The rest had two to ten separate diagnoses. Therefore,
      96.4% also needed other gynecologic procedures at the time of hysterectomy--4842
      other operative procedures during 1925 abdominal hysterectomies, and 2356
      associated operative procedures during 864 vaginal hysterectomies. Prior to the
      time of hysterectomy, 15.07% of these patients had had major gynecologic
      operations, but after hysterectomy (+ +) only 2.9% needed any subsequent
      gynecologic operations. We conclude that among gynecologic patients, chart
      reviews or coding systems which are based only on a single diagnosis, or computer
      systems which are limited to 2, 3, or 4 diagnoses, will usually be incomplete,
      inaccurate, and misleading.

PMID- 1979288
TI  - Sequential Gn-RH superagonist and medroxyprogesterone acetate treatment of
      uterine leiomyomata.
AB  - A group of 48 women with symptomatic leiomyomata were treated during 6 months
      with the short-acting Gn-RH superagonist analog buserelin. The first (group C)
      was followed up for an additional six months of no medication. The second (group
      M) was treated for 6 additional months with medroxyprogesterone acetate (MPA) at
      doses decreasing from 200 to 25 mg/day. Buserelin therapy significantly decreased
      uterine size (P less than 0.001) in all patients, the average final volume being
      48.5% of the original (from 262 +/- 147 ml to 127 +/- 85.4 ml). In group C there
      was a significant (P less than 0.001) re-growth during the post-treatment
      observation period (from 120 +/- 81.0 ml to 198 +/- 77.2 ml); a significant (P
      less than 0.01) re-growth was also observed in group M during MPA medication
      (from 132 +/- 77.2 ml to 170 +/- 96.0 ml). The agonist had also a marked effect
      on fibroids: on average they decreased from 75.1 +/- 74.3 ml to 24.7 +/- 23.3 ml
      (P less than 0.025). In group C during the post-buserelin period of observation
      without treatment, there was a significant re-growth from 23.7 +/- 21.6 ml to
      47.7 +/- 27.5 ml (P less than 0.001), whereas in group M treatment with MPA
      prevented any significant re-growth (from 25.6 +/- 24.8 to 30.6 +/- 32.9 ml; P
      greater than 0.3).

PMID- 1979289
TI  - Study of Norplant implants in Shanghai: three-year experience.
AB  - A clinical follow-up study conducted in Shanghai, China confirmed earlier reports
      that the Norplant implants, Norplant-1 and Norplant-2, are both highly effective
      with high continuation rates. The implants, however, tend to cause menstrual
      disturbance, spotting and bleeding. The mean hemoglobin value, however, did not
      change and the blood pressure remained stable. The report of 8 cases of
      thrombocytopenia among 301 Norplant-2 users is a source of concern.

PMID- 1979290
TI  - Combined intrauterine and tubal pregnancy after in vitro fertilization and embryo
      transfer.
AB  - A case of combined intrauterine and tubal pregnancy after in vitro fertilization
      and embryo transfer is reported. As soon as the diagnosis was made at 9 weeks
      gestation, the fetal heart movement of the tubal pregnancy disappeared, and the
      patient was managed without surgery throughout the pregnancy course. After an
      infant was delivered, a right salpingectomy was performed and the diagnosis was
      histologically confirmed. Risk factors and treatments of combined pregnancy are
      discussed.

PMID- 1979291
TI  - Bilateral tubal and twin pregnancies in Ile-Ife, Nigeria.
AB  - Three cases of unilateral tubal twin pregnancies and four cases of simultaneous
      bilateral tubal pregnancy recorded in a Nigerian University Teaching Hospital
      were reviewed. The incidences were 1 in 68 and 1 in 51 ectopic pregnancies
      respectively. High twinning rates within the environment and tubal damage from
      pelvic infections were considered as possible etiologic factors.

PMID- 1979292
TI  - Induction of ovulation and pregnancy following lateral oophoropexy for Hodgkin's
      disease.
AB  - Present therapy for Hodgkin's disease which primarily affects young patients may
      produce long term remissions in more than 50% of cases. Potential injuries to the
      reproductive system from radiation or chemotherapy are significant considerations
      in therapeutic planning. Assessment of the effects of infradiaphragmatic
      radiation on germ cells may avoid ovarian ablation in women of reproductive age.
      This report addresses ovarian function and fertility following lateral
      oophoropexy and repositioning for Hodgkin's disease.

PMID- 1979293
TI  - Schmidt's syndrome: a rare cause of puberty menorrhagia.
AB  - Schmidt's syndrome, also known as polyglandular deficiency syndrome, is the
      presence of Addison's disease and hypothyrodism in a single patient. It is
      usually associated with other autoimmune disorders like vitiligo, diabetes
      mellitus, myasthenia gravis. A rare case of an 18-year-old girl having Schmidt's
      syndrome and vitiligo who presented with puberty menorrhagia is reported. A brief
      review of the literature is also given.

PMID- 1979294
TI  - Receptor-mediated regulation of calcium channels and neurotransmitter release.
AB  - Ca2+ influx into the nerve terminal is normally the trigger for the release of
      neurotransmitters. Many neurons possess presynaptic receptors whose activation
      results in changes in the quantity of neurotransmitter released by an action
      potential. This paper reviews studies that show that presynaptic receptors can
      regulate the activity of Ca2+ channels in the nerve terminal, resulting in
      changes in the influx of Ca2+ and in neurotransmitter release. Neurons possess
      several different types of voltage-sensitive Ca2+ channels. Ca2+ influx through N
      type channels appears to trigger transmitter release in many instances. In other
      cases Ca2+ influx through L channels can influence transmitter release.
      Neurotransmitters can inhibit N channels through a G protein-mediated
      transduction mechanism. The G proteins are frequently pertussis toxin substrates.
      Inhibition of N channels appears to involve changes in their voltage dependence.
      Neurotransmitters can also regulate neuronal K+ channels. Activation of these K+
      channels can lead to a reduction in Ca2+ influx and neurotransmitter release;
      these effects are also mediated by G proteins. Thus neurotransmitters may often
      regulate both presynaptic Ca2+ and K+ channels. These two effects may be
      synergistic mechanisms for the regulation of Ca2+ influx and neurotransmitter
      release.

PMID- 1979295
TI  - Floral homeotic mutations produced by transposon-mutagenesis in Antirrhinum
      majus.
AB  - To isolate and study genes controlling floral development, we have carried out a
      large-scale transposon-mutagenesis experiment in Antirrhinum majus. Ten
      independent floral homeotic mutations were obtained that could be divided into
      three classes, depending on whether they affect (1) the identity of organs within
      the same whorl; (2) the identity and sometimes also the number of whorls; and (3)
      the fate of the axillary meristem that normally gives rise to the flower. The
      classes of floral phenotypes suggest a model for the genetic control of
      primordium fate in which class 2 genes are proposed to act in overlapping pairs
      of adjacent whorls so that their combinations at different positions along the
      radius of the flower can specify the fate and number of whorls. These could
      interact with class 1 genes, which vary in their action along the vertical axis
      of the flower to generate bilateral symmetry. Both of these classes may be
      ultimately regulated by class 3 genes required for flower initiation. The
      similarity between some of the homeotic phenotypes with those of other species
      suggests that the mechanisms controlling whorl identity and number have been
      highly conserved in plant evolution. Many of the mutations obtained show somatic
      and germinal instability characteristic of transposon insertions, allowing the
      cell-autonomy of floral homeotic genes to be tested for the first time. In
      addition, we show that the deficiens (def) gene (class 2) acts throughout organ
      development, but its action may be different at various developmental stages,
      accounting for the intermediate phenotypes conferred by certain def alleles.
      Expression of def early in development is not necessary for its later expression,
      indicating that other genes act throughout the development of specific organs to
      maintain def expression. Direct evidence that the mutations obtained were caused
      by transposons came from molecular analysis of leaf or flower pigmentation
      mutants, indicating that isolation of the homeotic genes should now be possible.

PMID- 1979296
TI  - The orthodenticle gene encodes a novel homeo domain protein involved in the
      development of the Drosophila nervous system and ocellar visual structures.
AB  - The orthodenticle (otd) locus of Drosophila is required for embryonic
      development, and null mutations of otd cause defects in head development and
      segmental patterning. We show here that otd is necessary for the formation of the
      embryonic central nervous system (CNS). otd mutations result in the formation of
      an abnormal neuropil and in the disappearance of identified neurons associated
      with the midline of the CNS. In addition, otd is allelic to ocelliless (oc), a
      mutation that causes the deletion of the ocelli of the adult fly. We have
      identified a transcription unit corresponding to the otd locus and find that it
      is expressed early in a stripe near the anterior pole of the cellular blastoderm
      and later in the region of the CNS from which these neurons normally arise. The
      predicted otd protein contains a well-conserved homeo domain and is therefore
      likely to be a transcriptional regulator involved in specifying cell fate both in
      the embryonic CNS and in the ocelli.

PMID- 1979297
TI  - abdA expression in Drosophila embryos.
AB  - The abdominal A (abdA) gene is one of three transcription units in the Bithorax
      Complex of Drosophila encoding a homeo box protein; it is flanked by
      Ultrabithorax (Ubx) and Abdominal B (AbdB). The abdA gene is required for
      segmental identity of the second through eighth abdominal segments. The
      transcription unit of abdA is approximately 20 kb long and encodes a protein of
      330 amino acids. The abdA homeo box is almost identical to the homeo box of Ubx
      but is quite different from the AbdB homeo box. A polyclonal antibody to abdA
      protein stains embryonic nuclei in segments A1-A7 (parasegments 7-13). The iab-2,
      3, and 4 mutant classes define positive cis-regulatory elements that induce
      expression of abdA in segments A2-A4 (parasegments 7-9), respectively. Once a
      pattern of abdA expression is turned on in a given parasegment, it remains on in
      the more posterior parasegments, so that the complex pattern of expression is
      built up in the successive parasegments. The abdA product appears to repress
      expression of Ubx whenever they appear in the same cell, but abdA is repressed by
      AbdB only in the eighth and ninth abdominal segments.

PMID- 1979298
TI  - Cloning of the Schwanniomyces occidentalis glucoamylase gene (GAM1) and its
      expression in Saccharomyces cerevisiae.
AB  - The Schwanniomyces occidentalis glucoamylase (GAM)-encoding gene (GAM1) was
      isolated from a lambda Charon4A genomic library using synthetic
      oligodeoxynucleotides as probes. GAM1 contains an ORF of 2874 nucleotides (nt)
      coding for 958 amino acids. S1 mapping revealed that the transcript has only a
      very short 5'-untranslated leader of 8-12 nt. Disruption and displacement of the
      GAM1 gene in Sc. occidentalis resulted in loss of the ability to grow on starch
      efficiently. The gam1 strains still exhibit low GAM activity suggesting that at
      least a second weakly expressed GAM-encoding gene (GAM2) is present in Sc.
      occidentalis. Expression of the Sc. occidentalis GAM1 gene in Saccharomyces
      cerevisiae was achieved after promoter exchange. S. cerevisiae cells transformed
      with centromere plasmids carrying the GAM1 gene fused to promoters of different
      S. cerevisiae genes, namely GAL1, PDC1 and ADH1, efficiently secrete GAM and are
      able to grow with soluble starch as a sole carbon source. The essential enzymatic
      properties of the GAMs secreted from S. cerevisiae and Sc. occidentalis are
      identical, although the modifications of the proteins are different.

PMID- 1979299
TI  - The cloning and functional characterization of the nifH gene of Rhodospirillum
      rubrum.
AB  - Dinitrogenase reductase (the nifH product) from Rhodospirillum rubrum is
      regulated by a post-translational modification system encoded by draTG. As
      demonstrated in this report, the cloning, sequencing, and functional
      characterization of the nifH gene provides a basis for further analysis as well
      as revealing interesting features of gene organization. The coding regions of
      nifH and draT are separated by only 400 bp, though the genes are divergently
      transcribed and differentially regulated. The construction of a nifH insertion
      caused a Nif- phenotype and destroyed the mutant's ability to synthesize both
      dinitrogenase and dinitrogenase reductase, verifying functionality and
      transcriptional organization of the nifHDK genes.

PMID- 1979300
TI  - The genome of Haemophilus influenzae Rd has a unique NotI site.
AB  - Previous analysis of physical maps of Haemophilus influenzae, which is circular
      and 1.9 Mb in length [Lee and Smith, J. Bacteriol. 170 (1988) 4402-4405; Kauc et
      al., J. Bacteriol. 171 (1989) 2474-2479], did not detect any NotI (GCGGCCGC)
      restriction sites. A transposon, Tn916, was constructed to contain a NotI linker
      cloned into its NciI site and introduced into the H. influenzae chromosome. NotI
      digestion of chromosomes containing a Tn916-associated NotI site followed by
      separation of fragments by field-inversion gel electrophoresis revealed the
      presence of two fragments obtained by two NotI cuts, one in Tn916 and the other,
      a unique, 'natural' NotI site in the original chromosomal DNA. The examination of
      other Haemophilus strains demonstrated the presence of one or more NotI sites in
      all of those tested.

PMID- 1979301
TI  - An improved method for the detection of Dcm methylation in DNA molecules.
AB  - The intrinsic insensitivity of EcoRII recognition sites in RF DNAs of phage M13
      and vector M13mp18 towards this restriction endonuclease can be overcome by
      adding site-specific oligodeoxyribonucleotide duplexes to the restriction sample.
      Since Dcm- DNA but not Dcm(+)-methylated DNA becomes susceptible under these
      conditions, this procedure constitutes an improvement of the Dcm methylation
      assay.

PMID- 1979302
TI  - Deletions at the N terminus of bacteriophage phi 29 protein p6: DNA binding and
      activity in phi 29 DNA replication.
AB  - Deletions corresponding to the first 5 or 13 amino acids (aa), not counting the
      initial Met, have been introduced into the N terminus of the phage phi 29 protein
      p6. The activity of such proteins in the in vitro phi 29 DNA replication system,
      their capacity to interact with the phi 29 DNA ends, and their interference with
      the wild type (wt) protein p6 activity have been studied. The initiation activity
      of protein p6 decreased considerably when 5 as were deleted and was undetectable
      when 13 aa were removed. The mutant proteins were unable to specifically interact
      with the phi 29 DNA ends. These results indicate the need of an intact N terminus
      for the activity of protein p6. However, such N-truncated proteins inhibited both
      the specific binding of the wt protein p6 to the phi 29 DNA ends and its activity
      in phi 29 DNA replication.

PMID- 1979303
TI  - Disruption of the gene XRN1, coding for a 5'----3' exoribonuclease, restricts
      yeast cell growth.
AB  - As a step toward determining the metabolic role(s) of a 5'----3' exoribonuclease
      (XRN1), a yeast gene, XRN1, encoding XRN1, was first cloned, then disrupted to
      test its essentially or effect on yeast cell growth. Clones in the high-copy
      number plasmid YEp24 cause overproduction (fivefold) of XRN1 in yeast cells, as
      measured by either poly(A) hydrolytic activity or immunoreactivity. Restriction
      mapping and deletion analysis showed that the XRN1 gene is located on a 6.7-kb
      XbaI-XhoI fragment of chromosome VII. The normal gene was disrupted in two
      haploid yeast strains by integrating a fragment with a BglII-deleted segment
      replaced with the yeast URA3 gene, and the disrupted strains lack XRN1.
      Successful transformation of haploid cells showed that the gene is not essential,
      but its absence markedly affected the cell growth rate. The growth defect is
      corrected by introduction of the XRN1 gene on a plasmid back into the disrupted
      yeast.

PMID- 1979304
TI  - Tardive dyskinesia: managing a common neuroleptic side effect.
AB  - Neuroleptics are useful medications for the treatment of psychosis and severe
      behavioral disturbances in the elderly. Unfortunately, older patients are at a
      high risk of developing deleterious side effects from these medications,
      especially persistent tardive dyskinesia (TD). Diagnosis, risk factors, and cause
      and treatment of TD are discussed. It is important to do a careful assessment as
      to the indications for neuroleptic use, monitor closely for the development of TD
      and other side effects, and work closely with the patient and family in making
      decisions about neuroleptic use.

PMID- 1979305
TI  - Ha-ras-1 alleles in Norwegian lung cancer patients.
AB  - We have examined DNA restriction fragment length polymorphisms (RFLP) of the Ha
      ras-1 gene in DNA from 118 lung cancer patients and 123 unaffected controls. When
      DNA samples were digested with MspI/HpaII restriction endonucleases. Southern
      blot analysis demonstrated 4 common, 4 intermediate and 7 different rare alleles
      in the combined population after hybridization to the pGDa1 probe. Six of the
      rare alleles were unique for the lung cancer group and 1 rare allele for the
      control group. The frequency of rare alleles in lung cancer patients (10/236) was
      significantly different (P less than 0.01) from the control group (1/246). The
      lung cancer group also had a significantly lower frequency of the common 2.57 kb
      fragment than the controls (P less than 0.02). The results thus indicate that Ha
      ras genotyping may be of value in lung cancer risk assessment.

PMID- 1979307
TI  - A new marker at DXS 115 useful for carrier detection in hemophilia A.
AB  - In this brief communication we report a new intergenic polymorphism at DXS115 as
      a marker for detection of heterozygotes in families at risk for hemophilia A.
      Total genomic DNA was isolated from white blood cells, double digested by KpnI
      and XbaI and hybridized with EcoRI/SstI fragment of the genomic probe p482.6. The
      incidence of the polymorphic 5.1-kb fragment was estimated as 0.069 in a German
      population. A technical advantage of using the XbaI/KpnI RFLP is that both the
      intragenic XbaI-RFLP in intron 22 of factor VIII gene and the new intergenic RFLP
      can be evaluated at the same time.

PMID- 1979306
TI  - Assignment of the Nance-Horan syndrome to the distal short arm of the X
      chromosome.
AB  - There are three types of X-linked cataracts recorded in Mendelian Inheritance in
      Man (McKusick 1988): congenital total, with posterior sutural opacities in
      heterozygotes; congenital, with microcornea or slight microphthalmia; and the
      cataract-dental syndrome or Nance-Horan (NH) syndrome. To identify a DNA marker
      close to the gene responsible for the NH syndrome, linkage analysis on 36 members
      in a three-generation pedigree including seven affected males and nine carrier
      females was performed using 31 DNA markers. A LOD score of 1.662 at theta = 0.16
      was obtained with probe 782 from locus DXS85 on Xp22.2-p22.3. Negative LOD scores
      were found at six loci on the short arm, one distal to DXS85, five proximal, and
      six probes spanning the long arm were highly negative. These results make the
      assignment of the locus for NH to the distal end of the short arm of the X
      chromosome likely.

PMID- 1979308
TI  - Cloning of the breakpoints of a deletion associated with choroidermia.
AB  - In order to characterize a previously described submicroscopic deletion
      encompassing (part of) the choroideremia (tapetochoroidal dystrophy: TCD) gene,
      we have cloned a 10.5-kb EcoRI fragment from the patient's DNA; this fragment
      carries the junction between both deletion endpoints ("junction fragment"). The
      distal portion of this fragment defines a new marker within, or just distal to,
      the TCD gene. This marker has been employed to confirm the diagnosis in several
      affected family members, and to rule out carriership in a female at risk with
      conspicuous clinical signs.

PMID- 1979309
TI  - Haplotype distribution and molecular defects at the phenylalanine hydroxylase
      locus in Italy.
AB  - In order to investigate the molecular basis of phenylketonuria (PKU) in Italy, we
      characterized the RFLP haplotypes at the phenylalanine hydroxylase gene in 38
      unrelated Italian PKU families. The distribution of haplotypes associated with
      PKU alleles differs from that of other European populations. In particular,
      haplotypes 1 and 6 are present in 39.7% and 17.6% of the PKU chromosomes, whereas
      the frequencies of haplotypes 2 and 3 are 5.9% and 2.9%, respectively. The
      characterization of PKU mutations using the polymerase chain reaction and allele
      specific oligonucleotides shows that 1 out of 2 haplotypes 3 carries the splicing
      mutation and that 2 out of 4 haplotypes 2 carry the missense mutation associated
      with these haplotypes in North European populations. Our results indicate that
      the two molecular defects most frequent in Northern Europe represent a minority
      of PKU mutations in Italy.

PMID- 1979310
TI  - The Na+/H+ antiporter: a "melt" polymorphism allows regional mapping to the short
      arm of chromosome 1.
AB  - The Na+/H+ antiporter is a ubiquitous membrane-associated protein that plays an
      important role in the regulation of intracellular pH. APNH, a gene encoding the
      antiporter, has been cloned and mapped to the short arm of chromosome 1 by in
      situ hybridization. Using the polymerase chain reaction, we have amplified a 376
      base pair fragment corresponding to the 5' end of APNH. We have detected a
      polymorphism within this fragment by denaturing gradient gel electrophoresis.
      Using polymorphisms at other 1p loci (ALPL, the gene for alkaline phosphatase, RH
      and D1S57), we have been able to map APNH telomeric to D1S57 and close to RH and
      ALPL by genetic linkage. APNH is a plausible candidate gene for human essential
      hypertension; the APNH polymorphism combined with a knowledge of its genetic map
      location allow this candidate to be tested in hypertensive kindreds and sib
      pairs.

PMID- 1979311
TI  - Localization of the gene for human proliferating nuclear antigen/cyclin by in
      situ hybridization.
AB  - Proliferating cell nuclear antigen (PCNA)/cyclin has been localized by in situ
      hybridization to the short arm of human chromosome 20 with a peak of grains over
      band 20p13. In addition, there were two strong secondary peaks of grains over
      11p15.1 and Xp11.4 indicating the presence of two related genes in man.

PMID- 1979312
TI  - An HhaI polymorphism is present in factor IX genes of Asian subjects.
AB  - Hemophilia B is caused by decreased factor IX procoagulant activity. An HhaI
      restriction site polymorphism near the factor IX gene has been detected by the
      polymerase chain reaction. Frequency and linkage data already observed in
      Caucasians are confirmed and the polymorphism is also prevalent in the factor IX
      genes of Black and Asian populations.

PMID- 1979313
TI  - Detection by denaturing gradient gel electrophoresis of a new polymorphism in the
      apolipoprotein B gene.
AB  - The apolipoprotein B gene is subject to mutations that may be important in
      coronary heart diseases. We have used polymerase chain reaction and denaturing
      gradient gel electrophoresis to characterize a single nucleotide substitution in
      the apolipoprotein B gene. This mutation affects amino acid 4311 of the protein
      and converts asparagine to serine. It was found in 24% of the 81 unrelated
      individuals analyzed. Moreover, another mutation was detected by sequencing in a
      single individual.

PMID- 1979314
TI  - Brain monoamines during footshock-induced aggression in paired rats.
AB  - Regional brain monoamine concentrations were investigated following footshock
      induced fighting behaviour in paired rats, by a spectrophotofluorometric method.
      The dopamine (DA) levels of the diencephalon-midbrain (DM), and that of the
      caudate nucleus (CN), were significantly augmented as compared to unshocked but
      paired rats, the increase being substantially more in DM. Noradrenaline (NA)
      concentrations of both DM and pons-medulla (PM) increased to almost similar
      extents, though the data remained statistically insignificant in comparison to
      controls. The 5-hydroxytryptamine (5HT) of both DM and PM, however, recorded a
      decrease, which was statistically significant in the latter brain area. The
      biochemical data are consonant with the reported facilitatory effect of central
      DA, and the inhibitory role of central 5HT, in experimental aggression. The
      observed changes in NA levels, for which a role in experimental aggression
      remains equivocal, may be due to the stress of footshock kept minimal due to the
      coping factor of fighting in response to the shock.

PMID- 1979316
TI  - Effect of some beta-blockers and procaine on adrenaline-induced pulmonary edema
      and lung surfactant activity in rats.

PMID- 1979315
TI  - Acute neurobehavioural toxicity of phosphamindon and its drug-induced alteration.
AB  - Phosphamidon, a systemic organophosphate insecticide, (1.4 mg/kg - dose 1/4th of
      LD50 given ip), produced several autonomic, neurological and behavioral effects
      in mice with peak effects being at 15 min. Similar dose in rats also abolished
      conditioned avoidance response. Pre-treatment with atropine, iproniazid, alpha
      methyl-p-tyrosine, p-chlorophenylalanine or thiosemicarbazide reduce many of
      these effects. This suggests that phosphamidon toxicity involves the central
      cholinergic, adrenergic, serotonergic and GABAergic systems in addition to
      peripheral cholinergic effects.

PMID- 1979318
TI  - Comparison of receptors for 987P pili of enterotoxigenic Escherichia coli in the
      small intestines of neonatal and older pig.
AB  - Enterotoxigenic Escherichia coli isolates that express 987P pili colonize the
      small intestine and cause diarrhea in neonatal (less than 6-day-old) but not in
      older (greater than 3-week-old) pigs. However, 987P+ E. coli isolates adhere in
      vitro to small-intestinal epithelial cells from pigs of both ages. This indicates
      that older pigs as well as neonatal pigs contain receptors for 987P pili and that
      resistance in older pigs is not due to a lack of intestinal receptors for 987P
      pili. In this study, we demonstrated that 3-week-old gnotobiotic pigs, like
      neonatal pigs, were colonized and developed diarrhea when challenged with 987P+
      E. coli. We compared 987P receptors in small-intestinal epithelial cell brush
      borders and in intestinal washes (luminal contents) from less than 1-day-old, 3
      week-old gnotobiotic, and 3- to 4-week-old weaned pigs. Samples were separated by
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis and blotted onto
      nitrocellulose filters, and 987P binding was demonstrated by immunoassay using
      purified 987P pili. Multiple 987P-binding components ranging from 33 to 40 kDa
      were found in brush borders from both 987P-susceptible (neonatal and gnotobiotic)
      and 987P-resistant (older) pigs: 987P binding to these receptors, which we called
      987R, did not correlate with 987P susceptibility. A less than 17-kDa 987P
      receptor, 987M, was found in the mucus fraction of intestinal washes from 987P
      resistant older pigs. Only trace amounts of 987M were detected in 987P
      susceptible neonatal and gnotobiotic pigs. 987M comigrated with the 987P receptor
      previously isolated from adult rabbits. Receptors for 987P in the mucus of older
      pigs may inhibit 987P-mediated intestinal colonization by preventing the
      attachment of 987P+ enterotoxigenic E. coli to intestinal epithelial receptors
      for 987P.

PMID- 1979317
TI  - Expression of Tac antigen component of bovine interleukin-2 receptor in different
      leukocyte populations infected with Theileria parva or Theileria annulata.
AB  - The Tac antigen component of the bovine interleukin-2 receptor was expressed as a
      Cro-beta-galactosidase fusion protein in Escherichia coli and used to raise
      antibodies in rabbits. These antibodies were used for flow cytofluorimetric
      analysis to investigate the expression of Tac antigen in a variety of Theileria
      parva-infected cell lines and also in three Theileria annulata-infected cell
      lines. Cells expressing Tac antigen on their surface were found in all T. parva
      infected cell lines tested whether these were of T- or B-cell origin. T cells
      expressing Tac antigen could be CD4- CD8-, CD4+ CD8-, CD4- CD8+, or CD4+ CD8+.
      Tac antigen expression was observed both in cultures which had been maintained in
      the laboratory for several years and in transformed cell lines which had recently
      been established by infection of lymphocytes in vitro with T. parva. Northern
      (RNA) blot analysis demonstrated Tac antigen transcripts in RNA isolated from all
      T. parva-infected cell lines. Three T. annulata-infected cell lines which were
      not of T-cell origin were also tested. Two of them expressed Tac antigen on their
      surface. Abundant Tac antigen mRNA was detected in these T. annulata-infected
      cell lines, but only trace amounts were demonstrated in the third cell line,
      which contained very few Tac antigen-expressing cells. In all cell lines tested,
      whether cloned or uncloned, a proportion of the cells did not express detectable
      levels of Tac antigen on their surface. This was also the case for a number of
      other leukocyte surface markers. In addition, we showed that the interleukin-2
      receptors were biologically functional, because addition of recombinant
      interleukin-2 to cultures stimulated cell proliferation. Recombinant interleukin
      2 treatment also resulted in increased amounts of steady-state Tac antigen mRNA.
      The relevance of interleukin-2 receptor expression on Theileria-infected cells is
      discussed.

PMID- 1979320
TI  - Human phagocytes have multiple lipid A-binding sites.
AB  - Bacterial lipopolysaccharide (LPS) is a potent stimulus of cells, yet a target
      protein for LPS has not been defined. We used two approaches to define LPS
      binding sites on cell surfaces: one assay measured binding of LPS-coated
      erythrocytes (ELPS) to cultured human cells, and a second measured binding of a
      radiolabeled probe, [32P]lipid IVA, to intact leukocytes. The first approach
      identified the CD11-CD18 family of integrins as lipid A-binding sites in human
      phagocytes, and the latter approach demonstrated saturable lipid A binding to
      intact murine macrophages, as well as to an approximately 95-kDa binding protein
      in purified membrane preparations. Because CD18 has a known molecular mass of 95
      kDa, we sought to determine whether the [32P]lipid IVA-binding site was CD18.
      Binding of ELPS and [32P]lipid IVA to human macrophages was found to differ with
      respect to temperature, divalent cation dependence, cellular specificity, and
      susceptibility to competition by polyanions. To determine whether the previously
      described 95-kDa lipid A-binding protein was CD18, nitrocellulose-immobilized
      RAW264.7 membrane proteins were probed with [32P]lipid IVA and subsequently
      immunoblotted with a monoclonal antibody to murine CD18. The lipid A-binding
      protein has an electrophoretic mobility slightly different from that of CD18.
      Moreover, monoclonal antibodies and polyclonal antiserum to the CD11-CD18 family
      of proteins did not inhibit lipid IVA binding to intact human macrophages.
      Finally, mononuclear cells from two patients with CD18 deficiency failed to form
      rosettes with ELPS but bound [32P]lipid IVA normally. Thus, different LPS
      preparations may bind to cells in a CD18-dependent or -independent manner. Since
      ELPS is particulate and lipid IVA is a fine dispersion, the identity of the
      binding site may depend on the physical state of the LPS.

PMID- 1979319
TI  - pap-2-encoded fimbriae adhere to the P blood group-related glycosphingolipid
      stage-specific embryonic antigen 4 in the human kidney.
AB  - A subtype of P fimbriae, encoded by the pap-2 gene cluster, has been analyzed for
      agglutination of erythrocytes and for binding to cryostat sections of the human
      kidney. We have demonstrated that pap-2-encoded fimbriae are capable of binding
      to erythrocytes from some animal species and to human erythrocytes which express
      globoside and the LKE (stage-specific embryonic antigen 4 [SSEA-4]) antigen. The
      pap-2 fimbriae bind to Bowman's capsule in the human kidney. Monoclonal
      antibodies directed against glycosphingolipids were used for the detection of
      specific P blood group-related antigens in the human kidney and on erythrocytes.
      Preincubation of kidney sections with monoclonal antibody MC813-70, which binds
      to the SSEA-4 antigen, inhibited adherence of purified pap-2-encoded fimbriae to
      Bowman's capsule. We suggest that one receptor for pap-2-encoded fimbriae is the
      antigen known as LKE (Luke) on human erythrocytes or SSEA-4 in the tissues.

PMID- 1979321
TI  - Conservation of Neisseria gonorrhoeae pilus expression regulatory genes pilA and
      pilB in the genus Neisseria.
AB  - The pili of Neisseria gonorrhoeae mediate bacterial adhesion to the host
      susceptible tissues. We have previously reported the identification of two genes,
      pilA and pilB, which act in trans to regulate pilus expression. Besides this
      regulatory function, pilA participates in an essential function for bacterial
      viability. Here we show that pilA and pilB homologs are also present in a variety
      of other members of the Neisseriaceae family of bacteria in contrast to the
      gonococcal pilin gene which hybridizes only to the pathogenic Neisseria species.

PMID- 1979322
TI  - Response of low and high protein select lines of pigs to the feeding of the beta
      adrenergic agonist ractopamine (phenethanolamine).
AB  - The effect of ractopamine, a phenethanolamine beta-adrenergic agonist, on growth,
      nutrient utilization and carcass composition was studied in two lines of pigs
      that were fed high (24%) or low (12%) protein diets. Of the two lines of pigs
      that had been selected for seven generations for rapid lean growth when fed
      either the higher (HS line) or low (LS line) protein diet, the HS line tended to
      exhibit a leaner carcass when fed either diet. Ractopamine, at 20 ppm in the
      diet, was fed from 60 kg live body weight until slaughter at 90 kg. When compared
      with their respective line-diet control group, the greatest response to
      ractopamine treatment was observed in the LS-12 group; at 90 kg, that group had
      31% less carcass lipid (P less than .05) and 17% more carcass protein (P less
      than .05). Considering the change that took place only between 60 and 90 kg live
      body weight, this translated into 57% less lipid and 59% more protein deposited
      in the carcasses with ractopamine treatment. This group also was 73% more
      efficient (P less than .05) in converting dietary protein to carcass protein but
      39% less efficient (P less than .05) in energy utilization. Response to
      ractopamine treatment was least by the LS-24 group, followed by the HS-12 and HS
      24 groups. A line x diet x treatment interaction (P less than .05) was noted for
      whole-carcass lipid, backfat, longissimus muscle area and efficiency of protein
      utilization.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1979324
TI  - The F pilus of Escherichia coli appears to support stable DNA transfer in the
      absence of wall-to-wall contact between cells.
AB  - Separation of HfrC-F- mating pairs of Escherichia coli by a filter 6 microns
      thick with straight-through pores 0.01 to 0.1 micron in diameter did not prevent
      DNA transfer. We conclude that the F pilus alone is capable of acting as a stable
      conduit for cell-to-cell DNA transfer.

PMID- 1979323
TI  - Role of the nac gene product in the nitrogen regulation of some NTR-regulated
      operons of Klebsiella aerogenes.
AB  - A positive, genetic selection against the activity of the nitrogen regulatory
      (NTR) system was used to isolate insertion mutations affecting nitrogen
      regulation in Klebsiella aerogenes. Two classes of mutation were obtained: those
      affecting the NTR system itself and leading to the loss of almost all nitrogen
      regulation, and those affecting the nac locus and leading to a loss of nitrogen
      regulation of a family of nitrogen-regulated enzymes. The set of these nac
      dependent enzymes included histidase, glutamate dehydrogenase, glutamate
      synthase, proline oxidase, and urease. The enzymes shown to be nac independent
      included glutamine synthetase, asparaginase, tryptophan permease, nitrate
      reductase, the product of the nifLA operon, and perhaps nitrite reductase. The
      expression of the nac gene was itself highly nitrogen regulated, and this
      regulation was mediated by the NTR system. The loss of nitrogen regulation was
      found in each of the four insertion mutants studied, showing that loss of
      nitrogen regulation resulted from the absence of nac function rather than from an
      altered form of the nac gene product. Thus we propose two classes of nitrogen
      regulated operons: in class I, the NTR system directly activates expression of
      the operon; in class II, the NTR system activates nac expression and the
      product(s) of the nac locus activates expression of the operon.

PMID- 1979325
TI  - Evidence for salt-associated restriction pattern modifications in the
      archaeobacterium Haloferax mediterranei.
AB  - DNA restriction pattern modifications were detected when Haloferax mediterranei
      was grown in low (10%) salt concentrations. After cells were grown again in
      optimal (25%) salt concentrations, the original pattern was recovered. These salt
      associated DNA modifications were revealed with 5% of the 160 DNA fragments
      cloned and used as probes in hybridization experiments. Patterns obtained when
      genomic DNA was digested with different restriction enzymes showed that these
      modifications are related not to insertions or deletions in genome but to
      modifications of some specific sequences.

PMID- 1979326
TI  - Surface orientation and antigen properties of Rh and LW polypeptides of the human
      erythrocyte membrane.
AB  - Time course digestion of intact human erythrocytes and right side-out vesicles
      with carboxypeptidase Y altered the Rh polypeptides and removed the 125I label
      that is normally incorporated by cell-surface radioiodination, but did not affect
      the RhD, Rhc, or RhE antigens. Under the same conditions, however, the LW
      antigens were rapidly destroyed. Digestion of inside-out and right side-out
      vesicles with aminopeptidase M was without any detectable effect on the Rh and LW
      antigens or polypeptides, although glycophorin A was degraded from right side-out
      but not from inside-out vesicles. These findings demonstrate that the C-terminal
      domain of the Rh and LW polypeptides is exposed at the external surface of human
      erythrocytes and indicate, in addition, that the LW antigens and tyrosine
      residue(s) of the LW and Rh proteins, respectively, are located close to the C
      termini of these polypeptides. Further studies using monoclonal and polyclonal
      antibodies showed that LW antigen expression is inhibited by treatment of red
      cells with EDTA and is selectively restored by Mg2+, but not by Mn2+ or Ca2+,
      whereas the Rh antigens were not affected under these conditions. In addition, O-
      and N-glycanase digestion of the LW glycoprotein removed its sugar chains, but
      did not alter significantly the epitopes recognized by the monoclonal anti-LW
      antibody.

PMID- 1979327
TI  - Protransglutaminase E from guinea pig skin. Isolation and partial
      characterization.
AB  - We have isolated protransglutaminase E, the zymogen form of epidermal
      transglutaminase E, from the skin of the adult guinea pig. This zymogen is the
      source of the large majority of soluble transglutaminase activity of skin. A
      molecular weight value for protransglutaminase E of 77,800 +/- 700, estimated by
      sedimentation equilibrium, is in close agreement with the apparent values
      determined by exclusion chromatography and by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. Treatment of the proenzyme with dispase,
      proteinase K, trypsin, or thrombin produces active enzyme. The enzyme,
      transglutaminase E, formed by the action of dispase, was observed to exist in the
      native state as a molecule indistinguishable in size from the zymogen. Under
      denaturing conditions, however, the enzyme dissociates into two fragments with
      molecular weights of 50,000 and 27,000. The observation that reducing agents are
      not needed for this dissociation suggests a noncovalent association of the two
      peptide chains in the native enzyme. Evidence that the catalytically essential 
      SH group of the enzyme residues in the Mr 50,000 fragment and that only the Mr
      27,000 fragment possesses an unmasked amino terminus provides the basis for a
      proposed model of zymogen activation. Whether the noncatalytic fragment plays a
      role in catalysis is not known because separation of the fragments of native
      enzyme was not achieved.

PMID- 1979328
TI  - A novel membrane-bound serine esterase in human T4+ lymphocytes immunologically
      reactive with antibody inhibiting syncytia induced by HIV-1. Purification and
      characterization.
AB  - A novel membrane-bound serine esterase, named tryptase TL2, which is
      immunologically reactive with the antibody inhibiting induction of syncytia by
      human immunodeficiency virus-1 (HIV-1) (Hattori, T., Koito, A., Takatsuki, K.,
      Kido, H., and Kutunuma, N. (1989) FEBS Lett., 248, 48-52), has been purified from
      a human T4+ lymphocyte clone. The enzyme has a molecular mass of 198 +/- 15 kDa,
      as judged by gel-permeation liquid chromatography, and is composed of two
      subunits of 32 kDa and four subunits of 28 kDa, as shown by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis. Studies with model peptide substrates
      showed that the enzyme preferentially recognized L-arginine and cleaved Boc-Gln
      Gly-Arg-4-methyl-coumaryl-7-amide and Boc-Gln-Ala-Arg-4-methyl-coumaryl-7-amide
      with high efficiency at a pH optimum of 8.5. The enzyme was strongly inhibited by
      the envelope glycoprotein gp 120 of HIV-1, by synthetic peptides with the
      sequence GPGR in their center, which corresponds to the principal neutralizing
      epitope of the gp 120s of various HIV-1 strains, by Kunitz-type inhibitors with
      the sequence GPCR in their active site, such as trypstatin, HI30, and [Arg15,
      Glu52]aprotinin and by the microbial inhibitors leupeptin and antipain. Studies
      on the subcellular distribution of tryptase TL2, immunohistochemical analysis,
      and cell surface radioiodination indicated that the enzyme is mainly localized in
      the plasma membrane.

PMID- 1979329
TI  - Partial recovery of lymphocyte activity in patients with colorectal carcinoma
      after curative surgical treatment and return of plasma glutamate concentrations
      to normal levels.
AB  - Glutamate was recently found to inhibit the membrane transport of cystine and to
      impair the function of macrophages and lymphocytes in vitro. Elevated plasma
      glutamate concentrations in patients with advanced carcinoma were also found to
      be quantitatively correlated with reduced lymphocyte reactivity in these persons.
      We now investigated the questions whether glutamate levels in tumor patients
      would decline to approximately normal levels after tumor resection and, if so,
      whether this would be correlated with a recovery of lymphocyte reactivity. We
      report that plasma glutamate levels as well as the concomitantly elevated plasma
      lactate levels of patients with colorectal carcinoma return to practically normal
      levels within 1 week after curative surgery. This is accompanied by a rapid
      recovery of the lymphocyte reactivity against concanavalin A. Lymphocyte
      responses against pokeweed mitogen and phytohemagglutinin, in contrast, remain
      impaired for at least 6 months, indicating that elevated glutamate levels in
      patients with colorectal carcinoma are associated with a long-lasting defect in
      the immune system.

PMID- 1979330
TI  - Polymerase chain reaction amplification of the constant and variable regions of
      the Bacteroides nodosus fimbrial gene.
AB  - Serogrouping of Bacteroides nodosus is based on antigenic differences in fimbriae
      of the different New Zealand prototype strains. Because of the time needed to
      isolate and grow pure cultures of B. nodosus and the difficulty in distinguishing
      between different serogroups because of cross-agglutination, a new DNA-based
      diagnostic approach based on the fimbrial gene sequence of B. nodosus was
      developed. Published nucleotide sequences of the fimbrial genes for serogroups A,
      G, D, and H showed conservation at the 5' end, coding for the N terminus, and
      variability at the 3' end, coding for the C terminus. The polymerase chain
      reaction was used to amplify both the constant and variable regions of the
      fimbrial genes. Constant-region oligonucleotide primers were used to amplify a
      100-base-pair fragment from the constant regions of the fimbrial genes of 10 New
      Zealand serogroups. Serogroup-specific oligonucleotide primers for serogroups A
      and H allowed amplification of a 282-base-pair fragment from serogroup A and a
      363-base-pair fragment from serogroup H. Thus, amplification of the constant and
      variable regions of the fimbrial gene allows rapid detection and grouping of B.
      nodosus.

PMID- 1979331
TI  - Characterization of prototype and clinically defined strains of Streptococcus
      suis by genomic fingerprinting.
AB  - A collection of Streptococcus suis strains from animal and human infections was
      examined for DNA-banding patterns after restriction endonuclease digestion and
      agarose gel electrophoresis. The endonuclease HaeIII produced the most
      discriminating restriction profiles among 23 serotypes studied. DNA from
      serotypes 9, 11, 12, and 16 was resistant to HaeIII cleavage. DNA from serotypes
      9 through 16 was cleaved with HindIII and showed substantial genomic differences.
      We also examined 106 epidemiologically unrelated strains isolated from cases of
      pig meningitis or pneumonia and 5 strains isolated from cases of human meningitis
      in order to compare genomic fingerprinting and serotyping as epidemiological
      tools. Heterogeneity was found among fingerprints of serologically identical
      isolates, indicating genetic diversity within some serotypes. DNA fingerprints of
      some serotype 2 strains from different sources appeared identical, suggesting a
      clonal relationship among strains of this serotype. The data suggest that this
      technique represents an important tool for examining the natural history of
      disease caused by S. suis.

PMID- 1979332
TI  - Identification of restriction fragment length polymorphisms in DNA from
      Mycobacterium paratuberculosis.
AB  - DNAs from 34 mycobactin-dependent isolates of Mycobacterium paratuberculosis and
      1 isolate of M. paratuberculosis 18 were digested with four restriction
      endonucleases. Southern hybridization experiments were performed with a 32P
      labeled oligonucleotide DNA probe derived from the sequence of IS900, an
      insertion sequence present in 15 to 20 copies per M. paratuberculosis chromosome.
      The probe hybridized with DNA from each of the mycobactin-dependent isolates, and
      restriction fragment length polymorphisms were detected among the isolates with
      each restriction endonuclease used. Restriction fragment length polymorphism
      analysis may permit identification of various strains of M. paratuberculosis,
      which has not been possible with other techniques.

PMID- 1979333
TI  - Basis for defective proliferation of peripheral blood T cells to anti-CD2
      antibodies in primary Sjogren's syndrome.
AB  - Anti-CD2-induced T cell proliferation was analyzed in the peripheral blood
      samples of 31 primary and 8 secondary untreated Sjogren's syndrome patients. Anti
      CD2-stimulated PBMC proliferation was very low in about one-third of primary
      Sjogren's syndrome samples, despite the number of CD2+ cells being similar in
      primary and secondary Sjogren's syndrome and normal PBMC samples. The depressed
      response to anti-CD2 was mainly found in anti-Ro+/La+ patients. Experiments on
      purified T cells demonstrated that a defect at the T cell level was responsible
      for the anti-CD2 unresponsiveness. Cell proliferation failure was associated with
      poor IL-2 and IL-2 receptor mRNA expression and, consequently, IL-2 and IL-2
      receptor synthesis. Since defective anti-CD2-induced mitogenesis could be
      reversed by phorbol myristate acetate, but not calcium ionophore A23187, it is
      probably correlated with impaired protein kinase C activation. Comparison of anti
      CD2-triggered PBMC proliferation in treated and untreated patients and a long
      term study of nine patients showed that the defect is a stable characteristic in
      primary Sjogren's syndrome patients, but that it can be reversed by
      pharmacological immunosuppression.

PMID- 1979334
TI  - Association between a T cell receptor restriction fragment length polymorphism
      and systemic lupus erythematosus.
AB  - The present study was designed to test the possibility that T cell receptor genes
      are associated/linked to those involved in systemic lupus erythematosus (SLE).
      Genomic DNA was isolated from 31 unrelated Caucasian SLE patients, 34 unrelated
      Caucasian normals, 5 multiplex American Caucasian SLE families, 9 multiplex
      Mexican SLE families, and 13 unrelated Mexican normals. The DNA was digested with
      Pst I, electrophoresed, and transferred to membranes by the Southern blot method.
      The blots were probed with a cDNA probe for the alpha chain of the T cell
      receptor. 13 polymorphic RFLP patterns were recognized. 1.3- and 3.0-kb band
      pairs were observed in 15 of 31 of American Caucasian patients and 4 of 34
      American Caucasian controls (chi square, 8.81; P less than 0.002; relative risk,
      7); there was no association of any RFLP pattern with Mexican SLE. The cDNA probe
      was cut with Rsa I, EcoR I, and Ava II into fragments corresponding to the V, J,
      C, and 3'UT regions. Only the fragment corresponding to the constant region
      reacted with the 1.3/3.0-kb band pair. These observations suggest that a genetic
      marker of the constant region of the alpha chain of the T cell receptor is
      associated with genes involved in SLE.

PMID- 1979335
TI  - A point mutation in transthyretin increases affinity for thyroxine and produces
      euthyroid hyperthyroxinemia.
AB  - In a family expressing euthyroid hyperthyroxinemia, an increased association of
      plasma thyroxine (T4) with transthyretin (TTR) is transmitted by autosomal
      dominant inheritance and is secondary to a mutant TTR molecule with increased
      affinity for T4. Eight individuals spanning three generations exhibited the
      abnormality. Although five of eight individuals had elevated total T4
      concentrations, all affected individuals were clinically euthyroid and all had
      normal free T4 levels. Purified TTR from the propositus had an affinity for 125I
      T4 three times that of control TTR. Exons 2, 3, and 4 (representing greater than
      97% of the coding sequence) of the TTR gene of DNA prepared from the propositus'
      peripheral blood leukocytes were amplified using the polymerase chain reaction
      (PCR) and were sequenced after subcloning. Exons 2 and 3 were indistinguishable
      from normal. In 50% of clones amplified from exon 4, a substitution of adenine
      (ACC) for guanine (GCC) in codon 109 resulted in the replacement of threonine-for
      alanine, a mutation confirmed by amino acid sequencing of tryptic peptides
      derived from purified plasma TTR. The adenine-for-guanine substitution abolishes
      one of two Fnu 4H I restriction sites in exon 4. PCR amplification of exon 4 of
      TTR and restriction digestion with Fnu 4H I confirmed that five affected family
      members with increased binding of 125I-T4 to TTR are heterozygous for the
      threonine 109 substitution that increases the affinity of this abnormal TTR for
      T4.

PMID- 1979336
TI  - Lack of 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase/isomerase in fibroblasts
      from a child with urinary excretion of 3 beta-hydroxy-delta 5-bile acids. A new
      inborn error of metabolism.
AB  - Cultured fibroblasts were shown to be capable of catalyzing the conversion of 7
      alpha-hydroxy-cholesterol to 7 alpha-hydroxy-4-cholesten-3-one, an important
      reaction in bile acid synthesis. The apparent Km was approximately 7 mumol/liter
      and Vmax varied between 3 and 9 nmol/mg protein per h under the assay conditions
      used. The assay was used to investigate fibroblasts from a patient who presented
      with a familial giant cell hepatitis and who was found to excrete the
      monosulfates of 3 beta, 7 alpha-dihydroxy-5-cholenoic acid and 3 beta, 7 alpha,
      12 alpha-trihydroxy-5-cholenoic acid in urine (Clayton, P. T., J. V. Leonard, A.
      M. Lawson, K. D. R. Setchell, S. Andersson, B. Egestad, and J. Sjovall. 1987. J.
      Clin. Invest. 79:1031-1038). In addition 7 alpha-hydroxy-cholesterol was found to
      accumulate in the circulation. Cultured fibroblasts from this boy were completely
      devoid of 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase/isomerase activity.
      Fibroblasts from his parents had reduced activity, compatible with a heterozygous
      genotype. The results provide strong evidence for the suggestion that this
      patient's liver disease was caused by a primary defect in the 3 beta-hydroxy
      delta 5-C27-steroid dehydrogenase/isomerase involved in bile acid biosynthesis.

PMID- 1979337
TI  - Molecular cloning and sequence of the complementary DNA encoding human
      mitochondrial acetoacetyl-coenzyme A thiolase and study of the variant enzymes in
      cultured fibroblasts from patients with 3-ketothiolase deficiency.
AB  - Complementary DNAs encoding the precursor of human hepatic mitochondrial
      acetoacetyl-CoA thiolase (T2) (EC 2.3.1.9) were cloned and sequenced. The cDNA
      inserts in these clones were 1,518 bases in length when overlapped, and encoded
      the 427-amino acid precursor of this enzyme (45,199 mol wt). This amino acid
      sequence included a 33-residue leader peptide moiety and a 394-amino acid subunit
      of the mature enzyme (41,385 mol wt). The T2 gene expression in fibroblasts from
      four patients with 3-ketothiolase deficiency was analyzed by Northern blotting.
      The T2 mRNA in all four cell lines had the same 1.7 kb as that of the control.
      However, the amounts of T2 mRNA differed: the content was reduced in two cell
      lines (cases 1 and 3), whereas it was within a normal range in others (cases 2
      and 4). Pulse labeling followed by subcellular fractionation revealed that the T2
      proteins in the fibroblasts from these patients are present in the mitochondria.
      These results suggest that different mechanisms are involved in the enzyme
      defects in the four patients.

PMID- 1979338
TI  - Phenotypic and functional characterization of T cells from patients with
      myasthenia gravis.
AB  - A study of cell surface phenotypes of PBL of myasthenia gravis (MG) patients
      showed that their T cells had a significantly higher percentage of 4B4+ T cells
      (the helper/inducer subset) than age- and sex-matched controls. The PBL of MG
      patients proliferated significantly higher than those of normal subjects (NS) in
      response to the purified alpha chain of the acetylcholine receptor (AChR). Anti
      AChR antibody was present in sera of 88% of MG and none of the NS. The PBL B
      cells from MG only, when cultured with autologous T cells and stimulated with
      either pokeweed mitogen (69%), or AChR-alpha chain (38%), secreted antibody to
      AChR-alpha chain, whereas T and B cells alone secreted no antibody. T cells from
      PBL of MG patients were more readily cloned than T cells of NS, by limiting
      dilution, in the presence of recombinant IL-2 and in the absence of AChR-alpha
      chain. About 50% of T cell clones from MG patients, compared to none from NS,
      proliferated to AChR-alpha chain. This response was HLA-DR restricted. MG T cell
      clones did not display significant cytotoxic activity, as compared to control T
      cell clones. Our results indicate that in MG, 4B4+ regulatory T cells play their
      role in the pathogenesis of MG, not by cytotoxicity, but more likely by their
      ability to stimulate specific antibody production by B cells.

PMID- 1979340
TI  - Immunocytochemistry of glutamate at the synaptic level.
AB  - High concentrations of glutaraldehyde (2-5%) were found optimal for fixation of
      glutamate. In the absence of glutaraldehyde, (para)formaldehyde does not
      permanently retain L-[3H]-glutamate or D-[3H]-aspartate previously taken up into
      brain slices. Rats were fixed by rapid transcardial perfusion with 2.5%
      glutaraldehyde/1% (para)formaldehyde, and brain samples osmicated, embedded in
      epoxy resin, sectioned, and exposed to specific antisera to glutamate (conjugated
      to carrier protein by glutaraldehyde), followed by colloidal gold-labeled second
      antibody. The gold particle density was higher over putative glutamatergic nerve
      terminals than over any other tissue elements (two to three times tissue average
      in cerebellum and hippocampus). Calibration by test conjugates containing known
      concentrations of fixed glutamate processed in the same fluid drops as the tissue
      sections indicated that the concentration of fixed glutamate in putative
      glutamatergic terminals in hippocampus CA1 was c. 20 mmol/liter. The grain
      density over the parent cell bodies was only slightly higher than the tissue
      average. (Grain densities over test conjugates of other amino acids, aldehyde
      fixed to brain macromolecules, were similar to that over empty resin. Labeling
      was blocked by glutamate-glutaraldehyde but not by other glutaraldehyde-treated
      amino acids.) In other experiments, brain slices were incubated in oxygenated
      artificial cerebrospinal fluid (CSF) and then immersion-fixed and processed as
      above. Here, the ration of grain densities in putative glutamatergic terminals vs
      other tissue elements was greater than in perfusion-fixed material. Comparison of
      intra-terminal areas poor and rich in synaptic vesicles suggested that in this
      preparation vesicles contained at least three times the glutamate concentration
      of cytosol. In the glutamatergic synapses of the giant reticulospinal axons in
      lamprey the ratio was over 30. Prolonged K+ depolarization of hippocampal and
      cerebellar slices reduced the nerve terminal glutamate immunoreactivity in a
      Ca2(+)-dependent manner. The results suggest that glutamate is released by
      exocytosis at excitatory synapses and show that immunocytochemistry can be used
      to study the cellular processing of small molecules.

PMID- 1979339
TI  - Human immunodeficiency virus-1 glycoproteins gp120 and gp160 specifically inhibit
      the CD3/T cell-antigen receptor phosphoinositide transduction pathway.
AB  - The interference of the recombinant HIV-1 glycoproteins gp160 and gp120 with the
      CD3/T cell antigen receptor (TcR)-mediated activation process has been
      investigated in the CD4+ diphtheria toxoid-specific human P28D T cell clone. Both
      glycoproteins clearly inhibit the T cell proliferation induced in an antigen
      presenting cell (APC)-free system by various cross-linked monoclonal antibodies
      specific for the CD3 molecule or the TcR alpha chain (up to 80% inhibition).
      Biochemical studies further demonstrate that exposure of the T cell clone to both
      glycoproteins (gps) specifically inhibits the CD3/TcR phospholipase C (PLC)
      transduction pathway, without affecting the CD3/TcR cell surface expression.
      Thus, inositol phosphate production, phosphatidic acid turnover, intracellular
      free calcium, and intracellular pH increase induced by CD3/TcR-specific MAbs are
      specifically impaired in gps-treated P28D T cells. Addition of purified soluble
      CD4 prevents binding of gps to T cells and overcomes all observed inhibitions.
      Maximal inhibitions are obtained for long-term exposure of the T cell clone to
      gps (16 h). No early effect of gps is observed. By contrast, gp160 and gp120 fail
      to suppress the CD2-triggered functional and biochemical P28D T cell responses.
      These results demonstrate that, in addition to their postulated role in the
      alteration of the interaction between CD4 on T lymphocytes and MHC class II
      molecules on APC, soluble HIV-1 envelope glycoproteins may directly and
      specifically impair the CD3/TcR-mediated activation of PLC in uninfected T cells
      via the CD4 molecule.

PMID- 1979341
TI  - Immunogold electron microscopic demonstration of glutamate and GABA in normal and
      deafferented cerebellar cortex: correlation between transmitter content and
      synaptic vesicle size.
AB  - Selective labeling of mossy fiber terminals and parallel fibers was obtained in
      rat cerebellar cortex by a glutamate antibody produced and characterized by
      Hepler et al. The high-resolution electron microscopic immunogold demonstration
      of this amino acid offered the possibility of determining the size and shape of
      synaptic vesicles in glutamate-positive mossy endings. Mossy terminals that
      stained with the glutamate antibody formed two distinct populations, one with
      spherical synaptic vesicles with an average diameter of 34.0 nm (more than 90% of
      all mossy fiber endings) and one with pleomorphic and smaller synaptic vesicles
      which had an average diameter of 28.5 nm. We present experimental evidence that
      the mossy terminals with large round vesicles are of extracerebellar origin,
      whereas those with small pleomorphic synaptic vesicles are endings of
      nucleocortical fibers. The presence of two distinct classes of gamma-aminobutyric
      acid (GABA)-containing axon terminals within cerebellar glomeruli has also been
      demonstrated; those originating from the cerebellar nuclei contain large (36.2
      nm) synaptic vesicles, whereas the majority of GABA-stained axon terminals that
      are of local (cortical) origin contain small (29.1 nm) synaptic vesicles. It
      therefore appears that, at least in the case of glutamate and GABA, morphological
      characterization of the axon terminals based on the size and shape of synaptic
      vesicles is not a reliable indicator of their functional nature (i.e., whether
      they are excitatory or inhibitory); convincing evidence for the identity of the
      transmitter can be obtained only by electron microscopic immunostaining
      procedures. Our results also suggest the existence of both inhibitory and
      excitatory feedback from cerebellar nuclei to cerebellar cortex.

PMID- 1979342
TI  - c-erbB-2 expression in breast cancer detected by immunoblotting and
      immunohistochemistry.
AB  - Evidence that the c-erbB-2 proto-oncogene is important in prognosis and
      oncogenesis in a number of human malignancies is increasing. DNA (Southern)
      hybridization and immunoblotting (Western) techniques are most commonly utilized
      to determine the amplification and protein expression of this proto-oncogene,
      respectively. These extraction techniques are often time consuming, costly, and
      subject to variability depending on the histological characteristics of the
      tumor. Immunohistochemistry (IHC), on the other hand, is more often time and cost
      effective. In addition, IHC may offer enhanced sensitivity over extraction
      techniques because of the in situ nature of analysis. In data presented here, 71
      cases of human mammary carcinoma were concomitantly assessed for c-erbB-2 gene
      copy number and oncoprotein expression by dilution DNA hybridization and IHC,
      respectively. In 65 (92%) of 71 cases, high-level expression was associated with
      gene amplification, whereas moderate or low-level expression was associated with
      a normal diploid gene copy number. In five of the six discrepant cases, IHC
      predicted amplification which was not corroborated by Southern analysis. In these
      cases, tumor mass was limited by the intraductal component of the lesion or by an
      abundance of stromal elements within the specimen. In 39 of the 71 total cases,
      Western immunoblotting was compared with IHC in the assessment of oncoprotein
      expression. Concordance was found in 33 (85%) of 39 cases. In four of the six
      discrepant cases, high levels of c-erbB-2 expression were demonstrated by IHC but
      not by immunoblotting. In these cases, intraductal disease and stroma-rich tumors
      again led to a relative paucity of neoplastic tissue within the specimens. We
      conclude that IHC offers a favorable alternative to either Southern analysis or
      Western immunoblotting in the assessment of c-erbB-2 gene copy number and
      expression levels of oncoprotein in human mammary carcinoma. Furthermore, IHC may
      prove advantageous to either extraction technique in specimens with limited tumor
      mass, such as biopsy materials, stroma-rich tumors, or early stage lesions such
      as intraductal carcinoma.

PMID- 1979343
TI  - Retroperitoneal fibrosis after surgery for aortic aneurysm in a patient with
      periarteritis nodosa: successful treatment with corticosteroids.
AB  - A 54-year-old man with hepatitis B virus-related periarteritis nodosa developed
      retroperitoneal fibrosis with bilateral hydronephrosis 2.5 months after placement
      of an aortobifemoral prosthesis for abdominal aortic aneurysm. Retroperitoneal
      fibrosis disappeared after treatment with corticosteroids. This observation is
      interesting in the light of the hypothesis that retroperitoneal fibrosis is
      caused by vasculitis.

PMID- 1979344
TI  - Treatment of drug-induced agranulocytosis with recombinant GM-CSF.
AB  - A 53-year male patient, treated for rheumatoid arthritis with sulphasalazine,
      developed a total agranulocytosis. When this state had prevailed for at least 10
      d no bone marrow granulocyte progenitor cells were detectable. Intravenous GM-CSF
      treatment was initiated 5 d later, and the patient recovered within the next 6 d.
      GM-CSF treatment for severe agranulocytosis deserves further investigation.

PMID- 1979345
TI  - Advances in treatment of anxiety and depressive disorders.

PMID- 1979346
TI  - Borna disease virus-induced meningoencephalomyelitis caused by a virus-specific
      CD4+ T cell-mediated immune reaction.
AB  - After intracerebral inoculation of Borna disease virus (BDV). Lewis rats develop
      a persistent infection of the central nervous system which is pathohistologically
      represented by perivascular encephalitic lesions predominantly in the grey
      matter. In previous studies it has been shown that a cell-mediated immune
      response causes Borna disease (BD). In order to define further the immune cell
      responsible for this immunopathological disease, a BDV-specific T cell line, NM1,
      was established and cultured in vitro. Phenotypically this T cell line was
      characterized by cytofluorometry as CD4-positive (CD4+). Proliferation assays
      with syngeneic and allogeneic antigen-presenting cells, and blocking experiments
      with monoclonal antibodies, revealed major histocompatibility complex class II
      antigens to be restriction elements. After passive transfer of this virus
      specific CD4+ T cell into immunosuppressed BDV-infected recipients, full-blown
      disease could be induced. Immunohistological examination of the cells involved in
      perivascular inflammatory infiltrates in BDV-infected rats and in recipients of
      the NM1 T cell line revealed a dominance of macrophages and CD4+ T cells. The
      presence of these cells in encephalitic lesions strongly suggests a delayed type
      of hypersensitivity reaction as the pathogenetic mechanism of BD.

PMID- 1979347
TI  - The extracellular domain of HER2/neu is a potential immunogen for active specific
      immunotherapy of breast cancer.
AB  - The proto-oncogene HER2/neu encodes a protein tyrosine kinase (p185HER2) that is
      homologous to the human epidermal growth factor receptor. Amplification and/or
      overexpression of HER2/neu occurs in multiple human malignancies and appears to
      be integrally involved in progression of some breast and ovarian cancers. Because
      of this fact, HER2/neu is an intriguing target for specific cancer therapeutic
      strategies. One such strategy is active specific immunotherapy, in which the
      immune system is targeted at specific antigens expressed by tumor cells. We have
      employed a transfected cell line that secretes the extracellular domain of
      p185HER2 as a source of HER2-derived immunogen in a guinea pig model. The
      immunized animals developed a cellular immune response, as monitored by delayed
      type hypersensitivity, and antisera derived from immunized animals specifically
      inhibited the in vitro growth of human breast tumor cells overexpressing
      p185HER2. These data provide support for an immunotherapeutic approach to cancers
      characterized by overexpression of the HER2/neu proto-oncogene.

PMID- 1979349
TI  - Clinical and laboratory effects of prolonged therapy with sulfasalazine, gold or
      penicillamine: the effects of disease duration on treatment response.
AB  - Serial observations for up to 5 years of clinical score (a subjective global
      assessment), serum C-reactive protein (CRP) and the erythrocyte sedimentation
      rate (ESR) were analyzed in 3 groups of patients with active rheumatoid arthritis
      (RA) requiring treatment with a second line drug. The groups comprised 315
      patients (243 women, 72 men) who had sulfasalazine (SAS); 203 patients (141
      women, 62 men) who had sodium aurothiomalate (gold) and 163 patients (131 women,
      32 men) who had penicillamine. The groups matched in most respects but the gold
      group had a smaller proportion of women, a shorter median disease duration and a
      higher median CRP than the remaining 2 groups. The penicillamine group contained
      a higher proportion of seropositive patients. In each group there were
      significant improvements in clinical score, CRP and ESR for all time points from
      6 to 30 months; these improvements were maintained for longer (up to 60 months
      for SAS) in the SAS and gold groups but the differences between the drugs after
      30 months were probably a consequence of falling number of patients, not
      differing drug potencies. The mean ESR and CRP levels fell to about 30 mm/h and
      20-30 mg/l, respectively. Response was defined as (1) treatment duration greater
      than 6 months, (2) clinical score improvement greater than 4 by 6 months, (3) ESR
      fall to less than 30 mm/h by 6 months. By these criteria 142 of 681 patients
      (20.9%) responded; the response rates were SAS 20.3%, gold 24.1%, penicillamine
      17.8%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1979348
TI  - Separation and growth of human CD4+ and CD8+ tumor-infiltrating lymphocytes and
      peripheral blood mononuclear cells by direct positive panning on covalently
      attached monoclonal antibody-coated flasks.
AB  - A direct positive panning technique was developed in order to achieve highly
      purified CD4+ and CD8+ cells. Fresh peripheral blood mononuclear cells or tumor
      infiltrating lymphocytes derived from bulk cultures were applied to modified
      polystyrene surfaces to which anti-CD4 or anti-CD8 monoclonal antibodies were
      covalently attached. Adherent cells were allowed to grow in the original flask
      and were then harvested and cultured in IL-2-containing medium. This positive
      immunoselection technique resulted in CD4+ and CD8+ cell subsets with high cell
      viability and a high degree of purity. In several samples, the isolated cell
      subsets were subsequently subjected to a negative immunomagnetic bead selection
      in order to remove reciprocal cell subset contamination or double-positive
      CD4+/CD8+ cells. The isolated cells maintained their ability to proliferate, kept
      their phenotypic profiles, and remained functionally intact after long-term
      growth in culture without the further addition of mitogenic or allogeneic cell
      stimulation. This approach is a simple, rapid, and reproducible technique that
      might be useful on a large scale to isolate and to grow T-cell subsets for
      research and for clinical use.

PMID- 1979350
TI  - Regulation of thyroid hormone receptor and c-erbA mRNA levels by butyrate in
      neuroblastoma (N2A) and glioma (C6) cells.
AB  - Butyrate produced a biphasic modulation of the thyroid hormone receptor in
      neuroblastoma N2A cells increasing receptor number by 20-35% at concentrations
      0.25-0.75 mM and decreasing receptor levels by 30-55% at 2-4 mM. The half-life of
      the receptor, as assessed by its disappearance after incubation with 18 microM
      cycloheximide was 8.4 hr in control cells and 10.3 hr and 5.0 hr in cells
      incubated with 0.25 and 4 mM butyrate, respectively. This compound increased the
      abundance of multyacetylated forms of histone H4 from 30% in control cells to
      almost 70% with butyrate 4 mM. In glioma C6 cells, the fatty acid produced a dose
      dependent increase of receptor levels (up to 3-4-fold with 2-5 mM butyrate) and
      had little effect in increasing multiacetylation (from 30% in controls to 42-46%
      with 2-5 mM butyrate). Recent studies have shown that the c-erbA proto-oncogen
      codes for the thyroid hormone receptor. In N2A and C6 cells, 2 c-erbA-related
      mRNAs, one measuring 2.6 kb and the other 6 kb, were detected. Both forms were
      differently regulated by butyrate. This compound decreased the abundance of the
      2.6 kb forms in both cell types, even at the concentrations at which there was an
      elevation of receptor levels. Only the largest mRNA correlated with receptor
      concentration increasing by 2-3-fold after treatment of C6 cells with butyrate,
      and undergoing a smaller but biphasic change in N2A cells. Our data suggest that
      modification of chromatin structure probably secondary to acetylation induces
      changes in thyroid hormone receptor levels in neuroblastoma and glioma cells by
      affecting both receptor stability and receptor mRNA levels.

PMID- 1979351
TI  - Developmental and regional expression of basic fibroblast growth factor mRNA in
      the rat central nervous system.
AB  - A cDNA clone encoding rat basic fibroblast growth factor (bFGF) was used as a
      hybridization probe to determine the level of bFGF mRNA during rat brain
      development as well as in different adult rat brain regions. In the rat brain, a
      3.7kb bFGF mRNA was detected together with lower levels of two minor bFGF mRNA
      species of 1.8kb and 1.5kb, respectively. The 3.7kb bFGF mRNA was detected in the
      rat brain already at embryonic day 16, the earliest time point tested. The
      embryonic brain contained 1.5 to 2 times higher levels of the 3.7kb bFGF mRNA
      than the adult brain. The amount of the 3.7kb bFGF mRNA in the adult rat brain
      was approximately 50 times higher than the level of beta-nerve growth factor mRNA
      in the rat brain. bFGF mRNA was found in all 12 brain regions tested in the adult
      rat brain with the highest level in colliculi, cerebral cortex, thalamus, and
      olfactory bulb. The lowest levels were found in pons and medulla oblongata. All
      three bFGF mRNA species showed the same regional distribution in the brain. In
      contrast to nerve growth factor mRNA, the level of bFGF mRNA in the neonatal
      hippocampus was slightly decreased 10 days after a cholinergic denervation by
      transection of the fimbria-fornix.

PMID- 1979352
TI  - Rapid, sensitive, and simple method for quantification of both neurotoxic and
      neurotrophic effects of NMDA on cultured cerebellar granule cells.
AB  - A simple and sensitive method adapted from the staining of living cells with
      fluorescein diacetate was developed to rapidly estimate the number of living
      cells remaining in a culture dish 24 hr after a few min of NMDA treatment of
      cerebellar neurons. This method consists of the measurement, after cell lysis, of
      the total amount of fluorescein produced from fluorescein diacetate by the living
      granule cells present in each culture dish. We show that this method can also be
      used to quantify the survival effect of chronic exposure of granule cells to
      either K+ or NMDA. In both cases, the fluorescence measured was found to be
      proportional to the number of fluorescein-labelled cells counted under a
      fluorescence microscope, indicating that the present method can be used to
      quantify both toxic and trophic effects of NMDA on cerebellar granule cells. This
      study confirms that these two NMDA effects occur at the same NMDA concentration,
      and both are inhibited by MK 801 in the same concentration range. We showed,
      moreover, that granule neurons developed in the presence of NMDA are much less
      sensitive to NMDA toxicity than neurons developed in K(+)-enriched medium.

PMID- 1979353
TI  - Properties of acetylcholinesterase in axolemma-enriched fractions isolated from
      bovine splenic nerve.
AB  - The properties of acetylcholinesterase (AChE) in axolemma-enriched fractions
      (AEF) from bovine splenic nerve were investigated to see if they differed in any
      way from those of the AChE in diaphragm muscle. The axolemmal enzyme had a low Km
      for acetylthiocholine (ca. 90 microM), exhibited substrate inhibition, and had a
      well-defined optimum of substrate concentration of 1 mM. The rate of hydrolysis
      of substrate decreased with increasing acyl chain length (acetyl- greater than
      propionyl- greater than butyryl-). The AChE inhibitors eserine and hexamethonium
      were competitive inhibitors of the membrane-bound enzyme, whereas lidocaine was a
      noncompetitive inhibitor; these results were comparable to the effect of these
      inhibitors on diaphragm muscle AChE. The axolemmal enzyme was more efficiently
      solubilized and more stable in nonionic detergents such as Triton X-100 and Tween
      20 than charged detergents such as lysolecithin and zwitterionic detergents.
      These results indicate that the AChE present in bovine splenic nerve AEF is
      identical to the previously characterized AChE from other sources.

PMID- 1979354
TI  - Advances in understanding trauma and burn injury. June 21-23, 1990, Washington,
      D.C. Proceedings.

PMID- 1979355
TI  - Immunomodulation of musk-moxa-string therapy in patients with scrofula.
AB  - The effects of musk-moxa-string therapy on the immune system in man were
      investigated in 39 patients with scrofula. Before treatment, the numbers of
      peripheral blood (PB) CD3+ and DC4+ cells and the ratio CD4+/CD8+ were found to
      be lower in patients with scrofula than in normal subjects, while those of B
      cells and DR+ cells were higher. Response of peripheral blood mononuclear cells
      (PBMC) to phytohemagglutinin (PHA) diminished in patients with scrofula. At month
      2-6 of musk-moxa-string therapy the number of PB CD8+ cells showed slight
      diminution along with significant increases in CD3+ and CD4+ cells and CD4+/CD8+
      ratio in total lymphocytes (P less than 0.001). In vitro a marked increased
      blastogenic response to mitogen stimulation with PHA was observed in PBMC of
      patients with scrofula after treatment (P less than 0.001). In contrast, B
      lymphocytes, monocytes, DR+ cells and blastogenic response to concanavalin A and
      pokeweed mitogen were not influenced by musk-moxa-string therapy.

PMID- 1979356
TI  - Action of thyrotropin-releasing hormone in experimental hemorrhagic shock-
      cardiovascular mechanism.
AB  - Thyrotropin-releasing hormone (TRH) could improve mean arterial pressure (MAP),
      myocardial contractile parameters (+/- dp/dtmax, Vpm and Vmax) and increase
      plasma epinephrine level significantly at 10 min after TRH administration in
      hemorrhagic shock rabbits, but the action of TRH on MAP and the myocardial
      contractility did not appear in rabbits pre-treated with reserpine (4 mg/kg, 24 h
      pre-treatment, i.v.). TRH had no effects on myocardial contractility and MAP at
      20 and 30 min after administration to rabbits pre-treated with beta-adrenergic
      blocker propranolol (1 mg/kg, 1 h before TRH injection i.v.), but it did exert
      effects on these parameters in rabbits pre-treated with alpha-adrenergic blocker
      phenoxybenzamine. Experiments in vitro showed that, although TRH (10(-4) M/L) had
      no direct effect on heart, left atrium and aortic strip, it did potentiate the
      inotropic effects of isoprenaline and dopamine on the left atrium. These results
      suggested that antishock effect of TRH is related to adrenergic system. TRH
      stimulates sympathomedullary system to secrete epinephrine and sensitize the beta
      receptors, but not alpha-receptors. Thus, TRH improves cardiac contractility,
      cardiac output and hemodynamics during hemorrhagic shock. The sensitization of
      the beta- and dopamine receptors played an important role in producing direct
      peripheral actions of TRH.

PMID- 1979357
TI  - Population and pedigree studies reveal a lack of association between the dopamine
      D2 receptor gene and alcoholism.
AB  - Using the dopamine D2 receptor clone lambda hD2G1, Blum et al recently found that
      the D2/Taq I allele (A1) was present in 69% of 35 deceased alcoholics but in only
      20% of an equal number of controls. To assess this association further, we
      evaluated the D2/Taq I polymorphism and a single-strand conformation polymorphism
      detected by polymerase chain reaction and nondenaturing gel electrophoresis (PCR
      SSCP) of the 3' noncoding region of the D2 receptor gene. We studied 40 unrelated
      white alcoholics, 127 racially matched controls, and two white pedigrees. The
      Schedule for Affective Disorders and Schizophrenia-Lifetime Version (SADS-L)
      clinical diagnostic interviews were rated blindly by two clinicians. The SADS-L
      interviews and other data were then used to ascertain diagnoses according to the
      Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition (DSM
      III-R) criteria. Alcoholics were subtyped according to age of onset, severity,
      presence of antisocial personality, and family history. No significant
      differences in either D2/Taq I or PCR-SSCP allele frequencies were observed
      between alcoholics, subpopulations of alcoholics, or controls. The PCR-SSCP
      polymorphism provided independent information against linkage at the D2 receptor
      locus. Several recombinants between the D2/Taq I locus and alcoholism were
      observed in two white families with an alcoholic parent who possessed the A1
      allele. This study does not support a widespread or consistent association
      between the D2 receptor gene and alcoholism.

PMID- 1979358
TI  - [Treatment of priapism with intracavernous injection of etilefrine
      hydrochloride].
AB  - A case of priapism following epidural anesthesia was reported. A 67 year old man
      received epidural anesthesia for the transurethral resection of a malignant
      bladder tumor. Epidural anesthesia which he had wanted to receive was given
      through the L3 to L4 intervertebral space with 18 ml of 2% lidocaine. The penile
      erection occurred while he was prepared and draped. Additional 8 ml of 1%
      lidocaine failed to overcome it and the operation cancelled. After this episode,
      he had anesthesia on 5 occasions in 2 years. General anesthesia was given 3 times
      without penile erection, but epidural block was tried on 2 occasions, which was
      followed by penile erection. For the penile erection, intracavernous injection of
      etilefrine hydrochloride was effective and surgical procedure could be done
      smoothly. The mechanism of priapism remained unclear but imbalance of the
      autonomic nervous system may be a involved. This case suggests that
      intracavernous injection of etilefrine hydrochloride is effective for treatment
      of penile erection during transurethral surgery.

PMID- 1979359
TI  - [Detection of tumor suppressor genes by use of RFLP markers].

PMID- 1979360
TI  - [Relations of glutamate and aspartate contents of the heart and its energy state
      after ischemia].
AB  - Ischemia and subsequent reperfusion with 5.5 mM glucose or sodium acetate were
      studied for impact on energy metabolism of the guinea pig isolated heart and
      glutamate, aspartate, and alanine levels in it and myocardial outflow. Acetate
      reperfusion resulted in a more significant reduction in the pool of adenine
      nucleotides and total creatine (phosphocreatine + creatine) by 48 and 60% of the
      baselines, respectively than did glucose reperfusion (as much as 65 and 76%
      reduction, respectively). The total glutamate and aspartate pool was twice as
      less as the baseline after reperfusion with any of the substrates, with acetate,
      tissue glutamate concentration was decreased by 42% of the baseline, whereas with
      glucose, it was reduced by as much as 62%. The consumption of amino acids was
      largely associated with their implication in alanine synthesis, which was
      stimulated by glycolysis/glucogenolysis at the early stage of reperfusion. The
      residue glutamate and aspartate contents in the reperfused hearts positively
      correlated with the pool of adenine nucleotides, total creatine, and the recovery
      of myocardial contractility. The findings suggest that the myocardial levels of
      these amino acids are closely associated with its energy state following ischemia
      and thus may affect the recovery of cardiac contractility.

PMID- 1979361
TI  - Sialyl-dimeric Lewis-X antigen expressed on mucin-like glycoproteins in
      colorectal cancer metastases.
AB  - Colorectal primary carcinomas and metastases from 20 Dukes' stage C or D patients
      were examined for the immunohistochemical localization and contents of various
      fucosylated N-acetyl-lactosamine oligomers by specific monoclonal antibodies
      (MAbs). MAbs used were SH1, specific for Lewis X antigen; FH4, specific for
      dimeric Lewis X antigen; FH6, specific for sialyl-dimeric Lewis X antigen; and
      KH1, specific for Lewis Y-Lewis X antigen. The distribution of the carbohydrate
      antigens identified by these MAbs was heterogeneous within the primary tumor as
      well as within the metastatic lesion. Examinations of serial sections indicated
      that areas within an individual tumor which were stained with one MAb were not
      always reactive with the other MAbs, although these four MAbs identify closely
      related structures. The degree of MAb reactivity with carcinoma sections was
      classified by percentage positive carcinoma cells, and primary tumors and
      metastases from the same patients were compared. An equivalent or higher
      proportion of carcinoma cells in the metastatic lesions were reactive with MAb
      FH6 than in the primary colon carcinomas, but each correlation was not seen with
      the other MAbs. Electrophoretic separation of tumor tissue extracts followed by
      staining with these MAbs revealed that a component having an approximate
      molecular weight of 1,000,000 is the major site for the binding of MAbs, FH6,
      FH4, and KH1. The electrophoretic mobility of the antigenic molecule on
      polyacrylamide gels as shown by direct MAb bindings was slightly different from
      that of a major sialomucin revealed by wheat germ agglutinin in the same tissues.
      MAb FH6 binding to a high molecular weight component was eliminated by prior
      treatment of the glycoprotein with mild acid or sialidase to remove sialic acid.
      Simultaneously, binding of MAb SH2, specific for dimeric Lex antigen, to this
      component increased. An extract was prepared from a liver metastasis, and high
      molecular weight components were isolated by gel filtration and then fractionated
      by DEAE-cellulose ion exchange chromatography. A fraction eluted from DEAE
      cellulose between 0.10-0.25 M sodium chloride contained most of the MAb FH6
      reactivity, as shown by antibody affinity chromatography. These results support a
      hypothesis that high molecular weight glycoproteins produced by colorectal
      carcinoma tissues are heterogeneous with regard to their carbohydrate chains and
      their antigenic structures may change during tumor progression.

PMID- 1979362
TI  - Optimization of immunocytochemical P-glycoprotein assessment in multidrug
      resistant plasma cell myeloma using three antibodies.
AB  - Seeking to optimize the immunocytochemical assay of P-glycoprotein, a 170
      kilodalton (P-170) molecule associated with multidrug resistance, we experimented
      with a variety of antibodies (JSB-1, C219, and MRK-16), fixation conditions, and
      titers using both human myeloma cell lines and clinical myeloma specimens. Under
      optimized conditions, using all three antibodies and the cell lines as standards
      and controls, the ICC method proved sensitive, specific, reliable, rapid, and
      within the realm of everyday hospital laboratory expertise. The 3 anti-P
      glycoprotein antibodies revealed different reactivities with P-170. Both C219 and
      JSB1 were optimized by fixation in cold acetone. With MRK-16 optimal results were
      obtained on unfixed or formalin fixed specimens. Under optimal fixation and
      titering conditions, low level (DOX 4) detection was possible. Given that the
      three antibodies differ in reactivity and recognize different P-170 epitopes, it
      follows that using the antibodies in a small panel is a useful strategy in
      increasing the likelihood of detecting true P-glycoprotein expression by the
      immunocytochemical method. In dilution experiments, the immunocytochemical method
      was as sensitive as RNase protection assay and more sensitive than Western blot
      detection. Immunocytochemistry coupled to computer-assisted single-cell
      densitometry, showed a strong correlation (R = 0.98) between cellular P-170
      density and in vitro resistance to doxorubicin. Multidrug-resistant specific
      probes for RNA expression and Western blot assays confirmed the specificity of P
      170 expression in both cell lines and clinical samples. Thus, a small panel of
      antibodies, under optimized immunocytochemical conditions, appears to have
      potential as a rapid, sensitive, clinically useful assay for multidrug resistance
      in myeloma.

PMID- 1979363
TI  - Breast milk and neonatal necrotising enterocolitis.
AB  - In a prospective multicentre study on 926 preterm infants formally assigned to
      their early diet, necrotising enterocolitis developed in 51 (5.5%). Mortality was
      26% in stringently confirmed cases. In exclusively formula-fed babies confirmed
      disease was 6-10 times more common than in those fed breast milk alone and 3
      times more common than in those who received formula plus breast milk.
      Pasteurised donor milk seemed to be as protective as raw maternal milk. Among
      babies born at more than 30 weeks' gestation confirmed necrotising enterocolitis
      was rare in those whose diet included breast milk; it was 20 times more common in
      those fed formula only. Other risk factors included very low gestational age,
      respiratory disease, umbilical artery catheterisation, and polycythaemia. In
      formula-fed but not breast-milk-fed infants, delayed enteral feeding was
      associated with a lower frequency of necrotising enterocolitis. With the fall in
      the use of breast milk in British neonatal units, exclusive formula feeding could
      account for an estimated 500 extra cases of necrotising enterocolitis each year.
      About 100 of these infants would die.

PMID- 1979364
TI  - Direct diagnosis of carriers of Duchenne and Becker muscular dystrophy by
      amplification of lymphocyte RNA.
AB  - Rapid detection of deletion and duplication mutations that cause Duchenne and
      Becker muscular dystrophy was achieved in patients and carriers after
      amplification of small amounts of mRNA from peripheral blood lymphocytes. The
      entire coding region of the dystrophin mRNA was amplified in 10 sections by
      reverse transcription and nested polymerase chain reaction, and the products were
      directly visualised on acrylamide minigels with ethidium staining. Major
      structural gene mutations were identified by the appearance of a band of
      different size to that of the wild type. The altered band was readily detected in
      all patients and heterozygous relatives. This non-radioactive test of venous
      blood samples can be used for unambiguous and rapid identification of virtually
      all carriers of deletions or insertions within the dystrophin gene.

PMID- 1979365
TI  - T-cell-directed hepatocyte damage in autoimmune chronic active hepatitis.
AB  - To investigate the function of activated T lymphocytes in autoimmune chronic
      active hepatitis, 7 of 15 T-cell clones from the peripheral blood of 8 patients
      were studied. These clones showed specificity for liver-membrane antigen with
      proliferation when stimulated by rabbit liver cell membranes. 6 of these clones
      reacted with liver-specific lipoprotein complex, and 1 clone (and 3 subclones)
      responded to the asialoglycoprotein receptor (ASGPR), both known targets of
      immune attack in autoimmune chronic active hepatitis. 2 of these clones
      stimulated autologous B lymphocytes to produce liver-membrane-specific
      autoantibodies and antibody to the ASGPR. These results suggest that liver
      membrane-specific activated T lymphocytes in peripheral blood may be important in
      the autoimmune attack of chronic active hepatitis.

PMID- 1979366
TI  - Deficiency of calcitonin gene-related peptide in Raynaud's phenomenon.
AB  - Skin biopsy samples from the fingers of nine patients with primary Raynaud's
      phenomenon, nine with the disorder associated with systemic sclerosis, and eleven
      healthy controls were examined by immunocytochemistry. There were no differences
      between the groups in the distribution of PGP 9.5 (a pan-neuronal marker)
      immunoreactivity, but there was a significant reduction in the number of
      calcitonin gene-related peptide (CGRP) immunoreactive neurons in the skin of
      patients with primary Raynaud's phenomenon and those with systemic sclerosis.
      These findings implicate dysfunction of the CGRP neurovascular axis in the
      pathophysiology of Raynaud's phenomenon.

PMID- 1979367
TI  - Serological and molecular survey for HTLV-I infection in a high-risk Middle
      Eastern group.
AB  - To define the extent of human T-cell leukaemia virus (HTLV-I) infection among a
      group of Jewish immigrants to Israel with an increased frequency of adult T-cell
      leukaemia, various serological and molecular screening methods, including enzyme
      linked immunosorbent assay (ELISA) for anti-HTLV-I, ELISA for antibody to
      recombinant HTLV-I p40tax protein, and molecular detection of infection by
      polymerase chain reaction (PCR) amplification of HTLV-I proviral DNA from
      peripheral blood mononuclear cell DNA, were used. By HTLV-I ELISA the overall
      rate of infection was 12% (24 of 208) among immigrants from Khurusan,
      northeastern Iran; no HTLV-I carriers were detected among 111 unselected Jewish
      immigrants from other parts of Iran. There was unexplained clustering of HTLV-I
      infection within a cohort of 32 elderly women of similar geographic origin in a
      home for old people--14 were seropositive by ELISA and 19 of 29 were positive by
      PCR. The findings in this newly identified high-risk population suggest that in
      addition to ELISA, other screening techniques may be required to detect all
      carriers in high-risk populations.

PMID- 1979368
TI  - Quinine-induced disseminated intravascular coagulation.
AB  - Recurrent disseminated intravascular coagulation occurred in 3 women after
      ingestion of quinine tablets for cramp. All had circulating quinine-dependent
      antibodies to platelets and in 2 there was initial evidence of antibody
      consumption, with low titres that rose steeply over the next few days and
      remained high for many months.

PMID- 1979369
TI  - Preliminary report: protection of cynomolgus macaques against simian
      immunodeficiency virus by fixed infected-cell vaccine.
AB  - Cynomolgus macaques were vaccinated with inactivated simian immunodeficiency
      virus-infected cells and 'Quil-A' as adjuvant at 0, 4, 8, and 36 weeks or at 0,
      4, 8, and 16 weeks. 2 weeks later these animals, together with a similar
      unvaccinated group, were challenged with 10 MID50 (50% monkey infectious doses)
      of a pool of SIVmac251 previously titrated in vivo. Virus was repeatedly isolated
      from unvaccinated animals on at least five separate occasions and proviral DNA
      was detected in circulating lymphocytes by polymerase chain reaction
      amplification. By contrast, virus and proviral DNA were not found in any of the
      vaccinated animals. However, the same vaccination regimen used after live virus
      challenge did not eliminate virus from previously infected macaques.

PMID- 1979370
TI  - Doctors' hours cut--hip, hip.

PMID- 1979372
TI  - Brewing a sausage.

PMID- 1979373
TI  - Mr Major's dream: is social mobility enough?

PMID- 1979371
TI  - AIDS vaccine: hope and despair.

PMID- 1979374
TI  - Indoor air pollution in developing countries.

PMID- 1979375
TI  - Neonatal screening and staggered early treatment for congenital dislocation or
      dysplasia of the hip.
AB  - In 14 264 consecutive newborn babies the results of screening and early treatment
      for congenital dislocation and/or dysplasia of the hip (CDH) were evaluated in a
      prospective follow-up study. Barlow's test was done and the family history was
      recorded. Babies who were positive (n = 140) were immediately given abduction
      treatment. If the screening result was doubtful (133) or if the test was negative
      but the family history positive (685) the child was radiographed at 5 months and
      abduction treatment was started if any form of CDH was seen. Among Barlow
      negative children with no family history (13,306), two reference groups were
      selected--at age 5 months (596) and at age 2 years (4365). Dislocation was missed
      at screening in 0.02%. Dysplasia was seen at 5 months in 15% of Barlow-negative
      children with a positive family history and in 2-3% of the reference group
      children. Crude estimates of the lower limits of validity indices for the
      screening test showed that the test is efficient in the identification of
      dislocation but probably has no value for dysplasia. Of the babies in whom
      treatment was started immediately 17% had relapse dysplasia after withdrawal of
      therapy, 3% had avascular necrosis, and 78% were normal at 2 years. When
      treatment was started at 5 months we found no relapse dysplasia, only 1%
      avascular necrosis, and 53-63% success at 2 years. In children with dislocatable
      hips we propose a wait-and-see treatment strategy, with early ultrasonography or
      radiography at 5 months.

PMID- 1979376
TI  - Controlled trial of immediate splinting versus ultrasonographic surveillance in
      congenitally dislocatable hips.
AB  - 79 infants with congenitally dislocatable hips diagnosed clinically soon after
      birth were examined sonographically and randomised in a controlled trial to
      immediate splinting (n = 41) or sonographic surveillance for 2 weeks (38).
      Infants from this second group were splinted at age 2 weeks if instability
      persisted (11 of 38) or if sonographic abnormality had shown no improvement (4 of
      38). Sonographic findings or clinical outcome did not differ between the two
      groups at birth or at 6 and 12 months' follow-up. We conclude that dislocatable
      hips may be safely watched for 2 weeks after birth to allow spontaneous
      resolution, but that this approach requires considerable resources and attention
      to detail. Our experience confirms the importance of the dynamic sonographic
      scan. The low specificity (70%) of sonographic examination in the first week of
      life makes it an unsatisfactory primary method of screening at birth, but it is a
      most useful adjunct to the clinical screening and management of congenital
      dislocation of the hip.

PMID- 1979377
TI  - US food legislation.

PMID- 1979378
TI  - UK food legislation.

PMID- 1979379
TI  - Is bracken a health hazard?

PMID- 1979380
TI  - Herbal remedies--an alternative.

PMID- 1979382
TI  - USA: Medigap.

PMID- 1979381
TI  - Lancet with less pain.

PMID- 1979384
TI  - All creatures great and very, very small.

PMID- 1979383
TI  - Duty of care to unborn child.

PMID- 1979385
TI  - Neuroectodermal tumours in children born after assisted conception.

PMID- 1979386
TI  - Percutaneous parietal pleurectomy for recurrent spontaneous pneumothorax.

PMID- 1979387
TI  - Intoxication from mercury spilled on carpets.

PMID- 1979388
TI  - Mercury from dental amalgam.

PMID- 1979389
TI  - Transmission of sarcoidosis via cardiac transplantation.

PMID- 1979390
TI  - Enhancement of recovery from psychiatric illness by methylfolate.

PMID- 1979391
TI  - Seizures associated with low-dose alpha-interferon.

PMID- 1979392
TI  - Toothpaste and Crohn's disease.

PMID- 1979393
TI  - Ketoconazole in visceral leishmaniasis.

PMID- 1979394
TI  - Is renal vasculitis increasing in incidence?

PMID- 1979395
TI  - Dogma, denial, and drinking problems.

PMID- 1979396
TI  - Living non-related kidney transplantation in Bombay.

PMID- 1979397
TI  - Inhibition of Helicobacter pylori by acetohydroxamic acid.

PMID- 1979398
TI  - Perception of bleeding risk and heparin prophylaxis.

PMID- 1979399
TI  - Tissue pressure, posture, and venous ulceration.

PMID- 1979400
TI  - Automated records and anaesthetic monitoring.

PMID- 1979401
TI  - World summit for children.

PMID- 1979402
TI  - Benzodiazepine prescribing in New York State.

PMID- 1979403
TI  - Ethics committees.

PMID- 1979404
TI  - The meaning of "screening".

PMID- 1979405
TI  - Lack of association between raised serum lipoprotein(a) and thrombolysis.

PMID- 1979406
TI  - Allergens in latex surgical gloves and glove powder.

PMID- 1979407
TI  - Gowers' shorthand.

PMID- 1979408
TI  - Role of endothelium-derived nitric oxide in maintenance of low fetal vascular
      resistance in placenta.

PMID- 1979409
TI  - Commercial immunoglobulins and HCV.

PMID- 1979410
TI  - Hepatitis A virus immunisation.

PMID- 1979411
TI  - Specificity of anti-HCV ELISA assessed by reactivity to three immunodominant HCV
      regions.

PMID- 1979412
TI  - Detection of Ebola-like viruses by immunofluorescence.

PMID- 1979413
TI  - Cerebral Pneumocystis carinii infection in AIDS.

PMID- 1979415
TI  - AIDS and migrant populations in Nicaragua.

PMID- 1979414
TI  - HIV-1, hepatitis (A,B, and C), and measles in Romanian children.

PMID- 1979416
TI  - Haptoglobin and free haemoglobin in pregnancy-induced hypertension.

PMID- 1979417
TI  - Acyclovir, herpes, and pregnancy.

PMID- 1979418
TI  - Pancoast's tumour due to aspergilloma.

PMID- 1979419
TI  - Safety of contrast echocardiography in screening divers.

PMID- 1979420
TI  - Electromagnetic fields and male breast cancer.

PMID- 1979421
TI  - Trends in prescribing of antihypertensive drugs in Australia, 1977-1987.
AB  - Prescribing of hypotensive agents, beta-blockers and diuretics was analysed using
      data from the Pharmaceutical Benefits Scheme, adjusted to reflect prescribing for
      hypertension, over 1977-1987. Prescribing of these three drug groups combined
      increased by approximately 50% over the period. Notable trends were decreased
      prescribing of bendrofluazide, chlorothiazide and methyldopa and increased
      prescribing of hydrochlorothiazide with amiloride, atenolol, metoprolol and
      prazosin, and, most recently, captopril and enalapril. The increase in
      prescribing of drugs for hypertension, combined with the choice of more expensive
      drugs, has resulted in a substantial increase in the drug costs associated with
      treating hypertension.

PMID- 1979422
TI  - Antioxidant and glutathione-related enzymatic activities in rat sciatic nerve.
AB  - The present work tries to establish the antioxidant capacity of the peripheral
      nervous tissue of the rat, in terms of the enzymatic activities present in this
      tissue that either prevent the formation of activated species as the semiquinone
      radical (DT-diaphorase), protect against activated oxygen species (superoxide
      dismutase, glutathione peroxidase), conjugate natural toxic products or
      xenobiotics (glutathione S-transferase, especially the activity conjugating 4
      hydroxy-nonenal), or complete the glutathione system metabolism (glutathione
      disulfide reductase, gamma-glutamyl transpeptidase). All the activities studied
      are lower in this tissue than they are in liver, except for gamma-glutamyl
      transpeptidase. The relevance of the results obtained and its possible
      relationship with different neuropathies is discussed. It is concluded that the
      peripheral nervous tissue is by far less protected than the liver against
      oxidative damage.

PMID- 1979423
TI  - HIV prevalence estimates and AIDS case projections for the United States: report
      based upon a workshop.
AB  - This document presents conclusions and recommendations from a workshop convened
      to discuss national estimates of human immunodeficiency virus (HIV) prevalence,
      acquired immunodeficiency virus (AIDS) case projections, and the proportion of
      HIV-infected persons with laboratory evidence of immune dysfunction. Appendices
      describe analyses performed before and after the workshop to estimate HIV
      prevalence and to predict future AIDS cases, the prevalence of persons with AIDS,
      and deaths among persons with AIDS. On the basis of these analyses, CDC estimates
      that approximately 750,000 persons in the United States were infected with AIDS
      at the beginning of 1986 and that approximately 1,000,000 Americans are currently
      infected with HIV. At least 40,000 new HIV infections occur each year among
      adults and adolescents, and an estimated 1,500-2,000 new infections occur each
      year among newborns as a result of perinatal HIV transmission. Approximately 60%
      of the estimated 1,000,000 HIV-infected persons in the United States may have T
      helper lymphocyte (CD4+ cell) counts of less than 500/mm3 of blood and may
      benefit from early treatment with zidovudine. The number of AIDS cases will
      continue to increase over the next 4 years, with a projection of 52,000-57,000
      cases to be diagnosed in 1990. Both AIDS case projections and HIV-prevalence
      estimates are influenced by the slowing of the rapid upward trend in AIDS
      incidence that occurred in 1987, particularly among homosexual and bisexual men
      who are not intravenous drug users. Data available during and after the workshop
      suggest that medical therapy or a decline in the incidence of new HIV infections
      among homosexual men in the early 1980s could have contributed to this change in
      trend, but the relative contributions of these and other factors (including
      changes in the completeness or timeliness of AIDS case reporting) require further
      study.

PMID- 1979426
TI  - [Dopamine and dopaminergic drugs as therapeutic agents in heart failure].

PMID- 1979424
TI  - The modulation of [3H]noradrenaline and [3H]serotonin release from rat brain
      synaptosomes is not mediated by the alpha 2B-adrenoceptor subtype.
AB  - The present study aimed at relating the presynaptic alpha 2-adrenoceptors, known
      to modulate noradrenaline and serotonin release, with the recently described
      alpha 2A- and alpha 2B-adrenoceptor subtypes. The effects of the agonist
      oxymetazoline (selective for alpha 2A subtype) and of three adrenoceptor
      antagonists (idazoxan, 1-(2-pyrimidinyl)piperazine (PmP) and prazosin, the last
      one known to be alpha 2B selective) were evaluated on [3H]noradrenaline and
      [3H]serotonin release in superfused synaptosomes from rat brain cortex. These
      drugs were also tested in [3H]yohimbine binding to human platelet membranes
      (containing only alpha 2A receptors) and to neonatal rat lung membranes
      (containing only alpha 2B receptors). The affinity pattern of these compounds at
      alpha 2A-adrenoceptors in binding studies was oxymetazoline greater than =
      idazoxan greater than PmP greater than prazosin; at alpha 2B-adrenoceptors it was
      idazoxan greater than = prazosin greater than PmP = oxymetazoline. Oxymetazoline
      inhibited with high and similar potencies the K(+)-evoked [3H]noradrenaline and
      [3H]serotonin release, IC50 18 and 7 nM, respectively; in the same conditions,
      the IC50 values of noradrenaline were 42 and 168 nM, respectively. The antagonist
      affinity pattern (antagonism against noradrenaline) was idazoxan greater than PmP
      greater than prazosin, either on [3H]serotonin release. These results indicate
      that presynaptic alpha 2 auto- or heteroreceptors do not belong to the alpha 2B
      subtype and suggest that the modulation of noradrenaline and serotonin release
      may be mediated by the alpha 2A-adrenoceptor subtype.

PMID- 1979427
TI  - A kinetic study of the rate of formation of dopamine, 3,4-dihydroxyphenylacetic
      acid (DOPAC) and homovanillic acid (HVA) in the brain of the rat: implications
      for the origin of DOPAC.
AB  - The rates of disappearance of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC)
      and homovanillic acid (HVA) in the brain of rats treated with the tyrosine
      hydroxylase inhibitor alpha-methyl-p-tyrosine were measured. Levels of dopamine.
      DOPAC and HVA in tissue were quantified in the striatum, nucleus accumbens and
      frontal cortex of the rat by means of high pressure liquid chromatography with
      electrochemical detection. Rats were sacrificed 1, 2 or 3 hr after the
      administration of alpha-methyl-p-tyrosine (200 mg/kg, i.p.). Levels of dopamine,
      DOPAC and HVA in tissue were logarithmically transformed, plotted against the
      duration of inhibition of tyrosine hydroxylase and the rate constant of the
      decline of dopamine and of its metabolites calculated. The rate constant of
      decline of DOPAC in each of brain studied was found to be greater than that for
      dopamine. The rate constant for the decline of dopamine was found to be greater
      in areas of the brain presenting the largest DOPAC/dopamine tissue ratios
      (frontal cortex greater than nucleus accumbens greater than striatum). The
      present results suggest that a substantial amount of DOPAC in brain derives from
      a newly formed pool of dopamine.

PMID- 1979425
TI  - Minimal alpha 1- and alpha 2-adrenoceptor-mediated coronary vasoconstriction in
      the anaesthetized swine.
AB  - alpha-Adrenoceptor-mediated coronary vasoconstriction contributes to the
      initiation and aggravation of experimental and clinical myocardial ischaemia.
      However, the extent of alpha 1- and alpha 2-adrenoceptor-mediated constriction
      has not been characterized in the porcine coronary circulation despite the
      frequent use of this experimental model. Fifteen swine were anaesthetized with
      either alpha-chloralose, enflurane or isoflurane to determine the amount of alpha
      adrenoceptor-mediated coronary constriction elicited by either the selective
      alpha 1-adrenoceptor agonist methoxamine or the selective alpha 2-adrenoceptor
      agonist azepexole. The left anterior descending coronary artery was cannulated
      and perfused by an external pump delivering constant blood flow from the carotid
      artery. Following bilateral cervical vagotomy and beta-adrenoceptor blockade with
      propranolol (2 mg kg-1), graded dosages of either one of the alpha-adrenoceptor
      agonists (9-45 micrograms kg-1 min-1) were infused into the coronary perfusion
      line while coronary arterial pressure (CAP) was measured through a distal side
      arm of the cannula to detect changes in coronary vascular resistance. Infusion of
      the alpha-adrenoceptor agonists was terminated when systemic arterial pressure
      increased. Sonomicrometers were used to measure anterior left ventricular wall
      thickening for the assessment of regional contractile function. During
      methoxamine infusion, no increase in vascular resistance was observed during
      alpha-chloralose, enflurane or isoflurane anaesthesia, whereas the infusion of
      azepexole increased CAP from 103 +/- 31 mmHg to 120 +/- 35 mmHg (alpha
      chloralose), from 101 +/- 16 mmHg to 122 +/- 11 mmHg (enflurane) and from 84 +/-
      20 mmHg to 94 +/- 19 mmHg (isoflurane), respectively.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1979428
TI  - The actions of the novel anti-aggressive drug eltoprazine on central neurones in
      the anaesthetised rat.
AB  - 5-Hydroxytryptamine (5-HT) and the novel anti-aggressive drug eltoprazine (1-(2,3
      dihydro-1,4-benzodioxin-5-yl) piperazine hydrochloride) were applied by
      microiontophoresis to spinal motorneurones and also to neurones in the brainstem
      which gave two distinctly different responses to 5-HT. In vitro
      microiontophoretic release studies showed that the electrophoretic mobility of
      eltoprazine and 5-HT were similar and that similar amounts of each drug would be
      applied by similar iontophoretic currents. Cells in the brainstem have been shown
      previously to be excited by 5-HT, acting at a 5-HT2 receptor. Eltoprazine only
      occasionally and weakly mimicked the excitatory effect of 5-HT on these cells.
      Although a potent antagonism of the 5-HT excitation by eltoprazine was observed,
      this was a non-selective effect, as responses to glutamate and D,L-homocysteic
      acid were also reduced. Cells in the lateral brainstem are depressed by 5-HT,
      acting on a receptor which has previously been shown to be of the 5-HT1-like
      group. At this receptor, 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)-tetralin) and
      5-carboxamidotryptamine, are potent agonists. Eltoprazine was a more potent
      depressant agonist than 5-HT on these brainstem neurones. The antagonist
      metergoline did not antagonise responses to either 5-HT or eltoprazine. It is
      suggested however that both drugs act at the same receptor to depress these cells
      because desensitizing the receptor by repeated, frequent applications of 5-HT
      abolished responses to 5-HT and eltoprazine, without altering responses to
      GABA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1979429
TI  - Synaptic potentials mediated by excitatory amino acid receptors in the nucleus
      accumbens of the rat, in vitro.
AB  - Focal stimulation of the dorsal regions of the nucleus accumbens of the rat, in
      vitro, evoked field potentials consisting of two negative waves. The first wave
      probably reflected electrical activation of the presynaptic fibres. This wave was
      resistant to excitatory amino acid antagonists and sulpiride. The second negative
      wave arose from a slower positive going component. These probably evince a
      population spike and field EPSP, respectively. Intracellular studies also
      indicated the occurrence of EPSP's and action potentials. The presumed field EPSP
      and population spike were reduced by kynurenic acid (IC50 approximately 300
      microM) but not by AP5 nor sulpiride. When the Mg2+ was removed, the field EPSP
      was prolonged in a manner fully reversible by the addition of 30 microM D(-)AP5.
      These results indicate that focal stimulation within the nucleus accumbens may
      activate excitatory amino acid-ergic fibres that make synaptic contact with an
      indigenous population of neurones. The postsynaptic receptors were probably of a
      non-NMDA subtype. However NMDA receptor-mediated responses were evident upon
      removal of the Mg2+, suggesting that these receptors could also contribute to
      neuronal excitation under the appropriate physiological conditions.

PMID- 1979430
TI  - Distribution of somatostatin mRNA in the rat nervous system as visualized by a
      novel non-radioactive in situ hybridization histochemistry procedure.
AB  - The cellular localization of preprosomatostatin mRNA in the rat brain and sensory
      ganglia has been examined in detail using a newly developed highly sensitive non
      radioactive in situ hybridization histochemistry procedure. An alkaline
      phosphatase labelled anti-sense 30mer oligodeoxynucleotide probe was used for
      detection of somatostatin mRNA. This probe readily demonstrated somatostatin gene
      expression throughout the rat CNS with very high contrast and good cellular
      localization. As a result, we visualized numerous somatostatin mRNA-positive
      cells in many CNS areas which had previously not been shown to contain a mRNA
      signal. This method detected a number of somatostatin mRNA-positive cells, in the
      mitral cell layer of accessory olfactory bulb, the glomerular layer of the main
      olfactory bulb, the dorsal part of the lateral septum, superficial gray layer of
      superior colliculus, inferior colliculus, anterior ventral cochlear nucleus,
      granular layer and Purkinje cell layer of cerebellum, and substantia gelatinosa
      of medulla and spinal cord, all areas where signal detection using radiolabelled
      in situ probes has previously been rather difficult. The principle advantages of
      the present method include the very precise cellular resolution of signal, the
      rapid reaction time and low background. The sensitivity of the present method
      seems to be at least equivalent to most immunocytochemical procedures and more
      sensitive than most isotopic in situ hybridization methods.

PMID- 1979431
TI  - Decreased tyrosine hydroxylase messenger RNA in the surviving dopamine neurons of
      the substantia nigra in Parkinson's disease: an in situ hybridization study.
AB  - Parkinson's disease is associated with a massive loss in melanized dopaminergic
      neurons in the substantia nigra resulting in a severe striatal dopaminergic
      denervation. The hyperactivity which develops in the remaining striatal
      dopaminergic terminals may be related to an increased rate of tyrosine
      hydroxylation. This could be related to changes in the level of expression of the
      gene coding for tyrosine hydroxylase. Thus, the detection of tyrosine hydroxylase
      messenger RNA was looked for at cellular levels by in situ hybridization
      histochemistry. Image analysis shows that the hybridization signal was
      significantly reduced in the surviving neurons when compared to control. The
      subnormal tyrosine hydroxylase messenger RNA content may express a change in
      level of tyrosine hydroxylase gene transcription, possibly in relation to
      sustained suffering of the neurons still present at late stages of the disease.

PMID- 1979432
TI  - Aspartate-like and glutamate-like immunoreactivities in the inferior olive and
      climbing fibre system: a light microscopic and semiquantitative electron
      microscopic study in rat and baboon (Papio anubis).
AB  - A post-embedding immunogold procedure was used to analyse, in a semiquantitative
      manner, the distributions of aspartate-like and glutamate-like immunoreactivities
      in the inferior olive and climbing fibre system in rats and baboons. The neurons
      in the inferior olive were uniformly labelled for aspartate as well as glutamate,
      indicating a 100% co-localization of these two amino acids in the cell bodies.
      The level of glutamate-like immunoreactivity in the climbing fibre terminals was
      similar to that in the parent cell bodies, as judged by a computer-assisted
      calculation of gold particle densities. In contrast, the level of aspartate-like
      immunoreactivity in the climbing fibre terminals was only one-seventh of that of
      the olivary neurons. No differences were found between the hemispheres and
      vermis. Nerve terminals in the inferior olive were generally moderately labelled
      with the aspartate antiserum, as were cell bodies of astrocytes. With a few
      exceptions, the results obtained in baboons were similar to those in rats.
      Notably, no evidence was found of an enrichment of aspartate-like
      immunoreactivity in climbing fibres. The present results do not support previous
      data suggesting that aspartate is the transmitter of the climbing fibres but
      indicate that glutamate or another excitatory compound should be considered as
      candidate for this role. Our findings show that the presence of aspartate-like
      immunoreactivity in cell bodies is an unreliable indicator of transmitter
      identity.

PMID- 1979433
TI  - Gene testing in the childhood spinal muscular atrophies.

PMID- 1979435
TI  - Immunopathology of cicatricial pemphigoid affecting the conjunctiva.
AB  - Conjunctival biopsy specimens from 13 patients with cicatricial pemphigoid and
      from 13 age-matched healthy individuals undergoing cataract surgery were analyzed
      by light microscopy and immunohistochemical techniques, including a panel of
      monoclonal antibodies used to characterize inflammatory mononuclear cell
      phenotypes. Results of histologic examination of cicatricial pemphigoid specimens
      showed typical squamous metaplasia, vasculopathy, increased numbers of mast
      cells, and abundant plasma cells. All cicatricial pemphigoid specimens
      demonstrated immunoreactants at the epithelial basement membrane zone (BMZ).
      Epithelium of cicatricial pemphigoid conjunctiva showed significantly more T
      helper cells (CD4+), dendritic cells (CD1+), and macrophages (CD14+), and a
      significantly higher helper/suppressor ratio than did controls. In the substantia
      propria, pemphigoid specimens showed dramatically increased inflammatory
      infiltrate with significantly more cells staining, in order of frequency, for T
      cells (CD3+, CD5+), T-helper cells (CD4+), T-suppressor cells (CD8+), macrophages
      (CD14+, Mac-1+), and dendritic cells (CD1+, HLA-DR+). Ten percent of these cells
      expressed interleukin-2 receptor protein (CD25+), indicating T-cell activation.

PMID- 1979434
TI  - Ocular rosacea. A histologic and immunopathologic study.
AB  - Acne rosacea is an idiopathic dermatologic disease that frequently produces
      conjunctival inflammation. The authors studied the histology and immunopathology
      of epibulbar conjunctival biopsy specimens from eight patients with ocular
      rosacea and compared the findings with those from conjunctiva from 13 normal
      individuals. The conjunctival epithelium in ocular rosacea was attenuated and
      infiltrated by inflammatory cells, mainly T-helper/inducer (CD4) cells,
      phagocytic cells, and antigen-presenting (CD14, Mac-1) cells. The difference
      between the normal control group and the rosacea group in the number of
      mononuclear cells forming these populations was statistically significant (P less
      than 0.01). The substantia propria of the rosacea specimens contained large
      subepithelial infiltrates of chronic inflammatory cells, and in some cases frank
      granuloma formation was evident. There was an overall mean increase of nearly all
      cell types, but especially of T-helper cells in the rosacea specimens compared
      with the controls. Interestingly, T-helper/inducer (CD4) cells, which were
      outnumbered by the T-suppressor (CD8) cells in the normal conjunctival epithelium
      (CD4/CD8 = 0.85), outnumbered the CD8-positive cells in the rosacea specimens
      (CD4/CD8 = 1.6). There also was a 3.5-fold increase of the CD4/CD8 ratio in the
      rosacea conjunctival stroma compared with the normal specimens. The mechanism
      involved in rosacea conjunctival inflammation resembles a type IV
      hypersensitivity reaction.

PMID- 1979436
TI  - Changes in selected brain neurotransmitters and their metabolites in the lamb
      after thyroidectomy during the last two trimesters of gestation or the early
      neonatal period.
AB  - To evaluate in a development context the effect of congenital hypothyroidism on
      concentrations of the neurotransmitters norepinephrine, dopamine, and serotonin
      (5HT) in selected brain areas of the ovine fetus, we studied the effect of
      thyroidectomy at three ages on the concentrations of these neurotransmitters and
      their major metabolites, homovanillic acid and 5-hydroxyindoleacetic acid.
      Fetuses underwent thyroidectomy at 90-95 or 105-115 d gestation (term = 147-150
      d) or 1-5 d after birth. Approximately 25 d after thyroidectomy, at d 120-125 or
      130-135 of gestation or 25-30 d after birth, respectively, the ewes were killed
      and fetal brains removed. Neurotransmitters and their metabolites were measured
      by HPLC with electrochemical detection. Thyroidectomy in the 2nd trimester
      increased 5HT in five brain areas: anterior hypothalamus, dorsal medial
      hypothalamus, pons, medulla, and cerebellum. Thyroidectomy in the 3rd trimester
      increased 5HT in the pons and medulla, increased norepinephrine in the dorsal
      medial hypothalamus and pons, and increased homovanillic acid in the posterior
      hypothalamus. Thyroidectomy in the newborn period decreased NE in the anterior
      hypothalamus, ventral medial hypothalamus, and midbrain, decreased 5
      hydroxyindoleactic acid in the posterior hypothalamus, lateral hypothalamus,
      dorsal medial hypothalamus, and ventral medial hypothalamus, and decreased
      homovanillic acid in the dorsal medial hypothalamus and ventral medial
      hypothalamus. From these data we conclude the following: 1) Hypothyroidism causes
      changes in neurotransmitter concentrations only in selected brain areas of the
      ovine fetus, rather than causing generalized and similar changes in all brain
      areas; and 2) 5HT 5-hydroxyindoleacetic acid concentrations are affected more
      often than the other neurotransmitters evaluated, perhaps because the 5HT
      neurotransmitter system is developing at these times.

PMID- 1979438
TI  - [Myocardial revascularization using the internal mammary artery].

PMID- 1979437
TI  - Alpha 1 (but not alpha 2)-adrenoceptor agonists in combination with the dopamine
      D2 agonist quinpirole produce locomotor stimulation in dopamine-depleted mice.
AB  - Mice were premedicated with reserpine and alpha-methyl-p-tyrosine to deplete
      stores of dopamine (DA) (and other neurotransmitters) and to stop DA (and
      noradrenaline (NA] synthesis. In DA-depleted mice, the mixed alpha 1/alpha 2
      agonist clonidine potentiated locomotor stimulation induced by a low dose of
      apomorphine as measured in automated activity cages. Clonidine and the slightly
      alpha 1-selective agonist ST587, but not ST91, an alpha-agonist which does not
      readily cross the blood brain barrier, produced marked stimulation when combined
      with the selective D2 agonist quinpirole. The D1 -selective agonist SKF38393 also
      produced marked excitation when combined with quinpirole. All the selective
      agonists, bar quinpirole which in some cases produced a significant locomotor
      stimulation, were relatively inactive when given alone. A "blind" observational
      analysis of the animals challenged with clonidine plus quinpirole indicated an
      increase in sniffing, rearing and shaking behaviour. In contrast, observation of
      the animals challenged with SKF38393 plus quinpirole indicated increased
      sniffing, rearing and biting and, in one case, increased grooming behaviour.
      Clonidine did not produce excitation (in automated cages) when combined with the
      selective D1 agonist SKF38393. The excitation produced by clonidine plus
      quinpirole was blocked by the selective D2 antagonist raclopride but not by the
      selective D1 antagonist SCH23390. The stimulation was also blocked by the alpha 1
      antagonist prazosin but not by the alpha 2 antagonists idazoxan or yohimbine.
      Biochemical analysis in the striata of mice challenged with clonidine plus
      quinpirole did not provide any obvious biochemical basis for the behavioural
      interaction. It is concluded that alpha 1 receptor agonists in combination with
      D2 DA agonists can produce marked stimulation in DA depleted mice.

PMID- 1979439
TI  - [The association of ankylosing spondylarthritis and periarteritis nodosa].

PMID- 1979440
TI  - Sequences of isopenicillin N synthetase genes suggest horizontal gene transfer
      from prokaryotes to eukaryotes.
AB  - Evolutionary distances between bacterial and fungal isopenicillin N synthetase
      (IPNS) genes have been compared to distances between the corresponding 5S rRNA
      genes. The presence of sequences homologous to the IPNS gene has been examined in
      DNAs from representative prokaryotic organisms and Ascomycotina. The results of
      both analyses strongly support two different events of horizontal transfer of the
      IPNS gene from bacteria to filamentous fungi. This is the first example of such a
      type of transfer from prokaryotes to eukaryotes.

PMID- 1979441
TI  - Selection of the T-cell repertoire in transgenic mice expressing a
      transplantation antigen in distinct thymus subsets.
AB  - Transgenic mice that expressed a transplantation antigen, H-2Kb, in an unusual
      tissue distribution have been developed. Gene-regulatory elements from the
      immunoglobulin heavy-chain locus (Emu enhancer and heavy chain promoter) were
      linked to the class I Kb gene and the construct microinjected into fertilized
      mouse eggs of a different haplotype. It was expected that such gene-regulatory
      elements would direct expression of the foreign class I molecules only to B and T
      lymphocytes. However, expression was also detected in a subset of thymus
      medullary epithelium. The Kb molecules expressed on this thymic subset were
      unable to positively select T cells for passage to the periphery. The mice were,
      however, tolerant of the cell types expressing the foreign Kb molecules and were
      also tolerant of Kb presented as skin grafts. These results suggest that not all
      components of thymic epithelium are involved in positive selection of T cells and
      that transplantation antigens expressed on non-dendritic cells can induce
      tolerance.

PMID- 1979442
TI  - Directed mutagenesis of the redox-active disulphide bridge in glutathione
      reductase from Escherichia coli.
AB  - Directed mutagenesis of the gor gene from Escherichia coli encoding the
      flavoprotein glutathione reductase was used to convert the two cysteine residues
      that comprise its redox-active disulphide bridge to alanine (C42A) and serine
      (C47S) residues. A double mutant (C42AH439A) was also created in which His-439,
      the proton donor/acceptor in the glutathione-binding site, was additionally
      converted into an alanine residue. The C42A and C47S mutants were both unable to
      catalyse the reduction of glutathione by NADPH. The C42A mutant retained the
      transhydrogenase activity of the wild-type enzyme, whereas the C47S mutant was
      also inhibited in this reaction. These results support the view that in the
      catalytic mechanism of E. coli glutathione reductase, the thiolate form of Cys-42
      acts as a nucleophile to initiate disulphide exchange with enzyme-bound
      glutathione and that the thiolate form of Cys-47 generates an essential charge
      transfer complex with enzyme-bound FAD. Titration of the C42A and C42AH439A
      mutants indicated that the imidazole side-chain of His-439 lowered the pKa of the
      charge-transfer thiol (Cys-47) from 7.7 to 5.7, enhancing its ability to act as
      an anion at neutral pH. Several important differences between these mutants of E.
      coli glutathione reductase and similar mutants (or chemically modified forms) of
      other members of the flavoprotein disulphide oxidoreductase family were noted,
      but these could be explained in terms of the different redox chemistries of the
      enzymes concerned.

PMID- 1979444
TI  - Endothelium-derived relaxing factor participates in the increased blood flow in
      response to pentagastrin in the rat stomach mucosa.
AB  - The stimulation of gastric-acid secretion by pentagastrin, a synthetic analogue
      of the endogenous peptide gastrin, is associated with an increased blood flow to
      the stomach mucosa, commonly referred to as functional hyperaemia. There are at
      least two potent vasodilator substances, the local release of which from
      endothelial cells could contribute to this hyperaemia, endothelium-derived
      relaxing factor (EDRF) and prostacyclin. EDRF has been identified as nitric
      oxide, released enzymatically from the guanidino group of L-arginine. In the
      present studies, the involvement of prostacyclin in the pentagastrin-induced
      increase in stomach blood flow was eliminated by using the cyclo-oxygenase
      inhibitor indomethacin. Thus this work was designed to elucidate the
      participation of EDRF/NO in the pentagastrin-induced hyperaemia and not its
      relative importance to prostacyclin. The increase in blood flow to the gastric
      mucosa in response to pentagastrin was measured by laser Doppler flowmetry in
      situ. Inhibition of EDRF/NO biosynthesis with the L-arginine analogues NG
      monomethyl-L-arginine (MeArg) or N omega-nitro-L-arginine (NO2Arg) significantly
      attenuated (by more than 80%) the increase in mucosal blood flow in response to
      pentagastrin. However, infusions of the natural substrate L-arginine reversed the
      inhibitor effect of MeArg on pentagastrin-induced increase in mucosal blood flow.
      Local intra-arterial injections of the endothelium-independent vasodilator
      glyceryl trinitrate produced a dose-related increase in blood flow to the rat
      stomach mucosa that was unaffected by infusion of MeArg. Thus, in the absence of
      prostacyclin, EDRF/NO participates in the pentagastrin-induced increase in blood
      flow to the rat stomach mucosa.

PMID- 1979443
TI  - Novel cell lines display properties of nociceptive sensory neurons.
AB  - Hybrid cell lines derived from neonatal rat dorsal root ganglia neurons fused
      with the mouse neuroblastoma N18Tg2 exhibit sensory neuron-like properties not
      displayed by the parental neuroblastoma. These properties include an inward
      (depolarizing) current with a conductance increase in response to activation of a
      bradykinin receptor, an inward (depolarizing) current with a conductance increase
      in response to the sensory excitotoxin capsaicin, the expression of sensory
      neuropeptides (substance P, CGRP and somatostatin), the expression of
      phosphatidylinositol-anchored molecules including adhesion molecules of the
      immunoglobulin superfamily that can be regulated in serum-free culture by nerve
      growth factor (N-CAM, F-3 and Thy-1), and low permissivity to herpes simplex
      virus infection. These lines thus provide appropriate models for the study of
      mechanisms involved in nociceptor activation and the regulation of expression of
      sensory-neuron specific markers including neuropeptides.

PMID- 1979445
TI  - Accumulation of laminin and microglial cells at sites of injury and regeneration
      in the central nervous system of the leech.
AB  - Profuse sprouting of leech neurons occurs in culture when they are plated on a
      substrate consisting of laminin molecules extracted from extracellular matrix
      that surrounds the central nervous system (CNS). To assess the role of laminin as
      a potential growth-promoting molecule in the animal, its distribution was
      compared in intact and regenerating CNS by light and electronmicroscopy, after it
      had been labelled with an anti-leech-laminin monoclonal antibody (206) and
      conjugated second antibodies. In frozen sections and electron micrographs of
      normal leeches the label was restricted to the connective-tissue capsule
      surrounding the connectives that link ganglia. Immediately after the connectives
      had been crushed the normal structure was disrupted but laminin remained in
      place. Two days after the crush, axons began to sprout vigorously and microglial
      cells accumulated in the lesion. At the same time, labelled laminin molecules
      were no longer restricted to the basement membrane but appeared within the
      connectives in the regions of neurite outgrowth. The distribution of laminin at
      these new sites within the CNS was punctate at two days, but changed over the
      following two weeks: the laminin became aggregated as condensed streaks running
      longitudinally within the connectives beyond the lesion. The close association of
      regenerating axons with laminin suggests that it may promote axonal growth in the
      CNS of the animal as in culture.

PMID- 1979446
TI  - The role of tyrosine at the ligand-binding site of the nicotinic acetylcholine
      receptor.
AB  - Identification of the critical residues in a receptor's ligand-binding site
      provides valuable structural information important for understanding the basis
      for ligand recognition. The design of specific ligands targeted for receptor
      action will depend to a great extent on detailed structural knowledge of this
      kind. Although the nicotinic acetylcholine receptor (nAChR) is perhaps the best
      characterized of all receptors, the detailed configuration of the ligand-binding
      site remains unknown. Structural comparisons of nicotinic agonists and
      antagonists have long predicted a negative subsite on the receptor to interact
      with the positively charged alkyl-ammonium moiety common to nearly all nicotinic
      agents. We have used intrinsic fluorescence spectroscopic analyses together with
      binding studies of selectively modified peptide fragments of the nAChR to suggest
      that one or two invariant tyrosine residues at positions 190 and 198 on the alpha
      subunit provide the critical negative subsite required for ligand binding.
      Tyrosines may similarly be part of the negative subsite of muscarinic receptors
      and other neurotransmitter receptors that bind cationic ligands.

PMID- 1979447
TI  - How to measure inclusive fitness.
AB  - Although inclusive fitness (Hamilton 1964) is regarded as the basic currency of
      natural selection, difficulty in applying inclusive fitness theory to field
      studies persists, a quarter-century after its introduction (Grafen 1982, 1984;
      Brown 1987). For instance, strict application of the original (and currently
      accepted) definition of inclusive fitness predicts that no one should ever
      attempt to breed among obligately cooperative breeders. Much of this confusion
      may have arisen because Hamilton's (1964) original verbal definition of inclusive
      fitness was not in complete accord with his justifying model. By re-examining
      Hamilton's original model, a modified verbal definition of inclusive fitness can
      be justified.

PMID- 1979448
TI  - An exploratory model of the impact of rapid climate change on the world food
      situation.
AB  - A simple, globally aggregated, stochastic-simulation model was constructed to
      examine the effects of rapid climatic change on agriculture and the human
      population. The model calculates population size and the production, consumption
      and storage of grain under different climate scenarios over a 20-year projection
      time. In most scenarios, either an optimistic baseline annual increase of
      agricultural output of 1.7% or a more pessimistic appraisal of 0.9% was used. The
      rate of natural increase of the human population exclusive of excess hunger
      related deaths was set as 1.7% per year and climatic changes with both negative
      and positive impacts on agriculture were assessed. Analysis of the model suggests
      that the number of hunger-related deaths could double (with reference to an
      estimated 200 million deaths in the past two decades) if grain production keeps
      pace with population growth but climatic conditions are unfavourable. If the rate
      of increase in grain production is about half that of population growth, the
      number of hunger-related deaths could increase about fivefold (over past levels);
      the impact of climatic change is relatively small under this imbalance. Even
      favourable climatic changes that enhance agricultural production may not prevent
      a fourfold increase in deaths (over past levels) under scenarios where population
      growth outpaces production by about 0.8% per annum. These results may foreshadow
      a fundamental change where, for the first time, absolute global food deficits
      compound inequities in food production and distribution in causing famine. The
      model also highlights the effectiveness of reducing population growth rates as a
      strategy for minimizing the impact of global climate change and maintaining food
      supplies for everyone.

PMID- 1979449
TI  - Towards clinical and epidemiological application of advances in molecular biology
      of Mycobacterium leprae.

PMID- 1979450
TI  - Traumatic injuries to teeth in Swedish children living in an urban area.
AB  - The prevalence of dental injuries in the permanent dentition was studied in a
      population comprising 1635 Swedish school children aged 7-15 years. A
      retrospective study of dental injuries in the deciduous dentition was also
      carried out. A total of 483 (30%) children in the material had experienced dental
      injuries. Twelve per cent of the injuries had been sustained before the age of 7
      years and 18 per cent after that age. The majority of injuries had occurred
      between the ages 3-10 years. In the permanent dentition, over 75 per cent of the
      injuries recorded had been sustained before the age of 11 years. Boys had a
      higher trauma frequency than girls, the sex ratio being 1.2:1 in the deciduous
      dentition and 1.6:1 in the permanent dentition. Thirty per cent of the injured
      deciduous teeth required some kind of treatment. The corresponding figure for the
      permanent dentition was 46 per cent.

PMID- 1979451
TI  - Enrichment of murine hematopoietic stem cells. Reconstitution of syngeneic and
      haplotype-mismatched mice.
AB  - A method is described to purify murine hematopoietic stem cells. The procedure
      involves fluorescence-activated cell sorting of nonadherent nucleated bone marrow
      cells for the presence of the antigen, Thy1.2, and the absence of the lineage
      specific antigens, Lyt2, L3T4, Mac1, B220, and J11D.2. These Thy1.2+T-B-M-J-
      cells are 200-800-fold enriched in in vitro colony-forming units. Moreover, this
      narrow subset shows enhanced ability to form spleen colonies and engraft lethally
      irradiated mice. Data reported herein demonstrate that these purified pluripotent
      stem cell populations also have enhanced potential for the rescue of lethally
      irradiated haplotype-mismatched mice.

PMID- 1979452
TI  - HLA-DR, DQ, and/or DP genotypic mismatches between recipient-donor pairs in
      unrelated bone marrow transplantation and transplant clinical outcome.
AB  - Sixteen recipient-donor pairs who underwent unrelated BMT were analyzed for their
      HLA-class II identity by DNA-RFLP, in order to evaluate the importance of the
      genotypic HLA-DR, DQ, DP identity in the clinical outcome of unrelated bone
      marrow transplantation. From our study, a clear correlation between the HLA-DR,
      DQ, and DP genetic identity and acute GVHD (aGVHD) is not obvious since the
      number of studied cases is still limited. Nevertheless, it seems that the genetic
      identity influence the clinical outcome and patient survival. Six patients out of
      the ten who experienced severe aGVHD (greater than grade II) differed from their
      respective donors by HLA-DP mismatch in the GVH direction. Two patients rejected
      their grafts, and both presented HLA-DP incompatibilities in both GVH and HVG
      directions. Hence, HLA-DP may function as a transplantation antigen like the
      other HLA-class II molecules (DR, DQ) in unrelated BMT. Accordingly, we propose
      considering it in the pretransplantation histocompatibility testing.
      Nevertheless, further studies with larger numbers of cases should be done in
      order to confirm the role of HLA-DP. No correlation was observed between the
      mixed lymphocyte reaction (MLR) reactivity and the incidence of aGVHD.
      Accordingly, MLR response seems to be an incomplete indicator of GVHD, and a
      functional test is still to be found.

PMID- 1979453
TI  - Renal allograft rejection in CD4+ T cell-reconstituted athymic nude rats. The
      origin of CD4+ and CD8+ graft-infiltrating cells.
AB  - PVG-rnu/rnu nude rats reject a fully allogeneic DA renal allograft after the
      adoptive transfer of naive CD4+ T cells alone, but rejection is accompanied by
      the accumulation of many CD8+ leukocytes within the graft. In order to clearly
      establish the provenance of these CD8+ cells infiltrating rejecting kidney
      allografts, nude recipients (PVG-RT7a) were injected with CD4+ T cells from the
      PVG-RT7b congenic strain bearing an allotypic variant of the leukocyte-common
      antigen. Dual fluorescence and immunohistochemistry demonstrated that
      approximately 75% of the total infiltrate was host-derived; the donor-derived
      RT7b population was almost entirely (92-99%) CD4+, CD5+, CD3+, and alpha beta
      TCR+. At least 97% of the CD8+ cells were of nude origin. There was no evidence
      of donor-derived CD8+ cells or of a CD4+8+ double-staining population.
      Unexpectedly, nearly half of the alpha beta TCR+ cells from the grafts were of
      nude origin.

PMID- 1979455
TI  - [Hantaan virus infections].

PMID- 1979454
TI  - Immunohistochemical expression of c-erbB-2 in human breast cancer by monoclonal
      antibody: correlation with lymph node and ER status.
AB  - c-erbB-2 Protein expression was investigated in a series of fifty primary breast
      cancers by means of a specific monoclonal antibody and immunocytochemistry.
      Specific staining was observed at the plasma membrane level of neoplastic cells,
      according to the reported localization of c-erbB-2 protein. Sixty-four percent of
      tumors scored positive, with a variable amount of stained cells. The rate of
      protein expression was found to exceed the reported gene amplification. No
      relationship was observed between c-erbB-2 protein staining and age, menopausal
      status or histologic subtypes. An inverse association was found between c'erbB-2
      protein staining and estrogen receptor content of tumors, assayed by
      immunocytochemistry. A positive relationship was observed between c-erbB-2
      protein expression and presence of axillary node metastasis. These findings
      suggest that c-erbB-2 protein expression is a marker of tumor aggressiveness and
      that its prognostic power deserves further investigation both in node-positive
      and node-negative patients.

PMID- 1979456
TI  - Increased renal scarring by bacteria with mannose-sensitive pili.
AB  - Renal scars are thought to be the end stage of chronic pyelonephritis and one of
      the most important causes of renal insufficiency and renal hypertension. The role
      of bacterial pili was examined in scar formation after an infection of newly
      constructed bacterial strains using the recombinant DNA technique, which
      possessed either mannose resistant (MR) or mannose sensitive (MS) pili of
      Serratia marcescens. Strains that differed in only a single virulence factor,
      namely, MR or MS pili, were used in a rat model of chronic pyelonephritis. In
      this model, MS-piliated bacteria stimulated renal scarring more severely than non
      piliated or MR-piliated bacteria.

PMID- 1979457
TI  - Correlations between natural resistance to doxorubicin, proliferative activity,
      and expression of P-glycoprotein 170 in human kidney tumor cell lines.
AB  - The natural resistance to doxorubicin of 15 human renal carcinoma cell lines was
      analyzed and compared to proliferative activity and expression of P-glycoprotein.
      We found a significant negative correlation between proliferative activity and
      natural resistance to doxorubicin, as well as between proliferative activity and
      the expression of P-glycoprotein. A positive correlation between resistance and
      expression of P-glycoprotein was found.

PMID- 1979458
TI  - [Monoclonal antibodies to the Karelian fever virus. The characteristics of their
      biological properties].
AB  - Biological properties of 6 variants of monoclonal antibodies (MAb) to Karelian
      fever virus, a member of the alpha-virus serocomplex Sindbis-WEE, produced by the
      available hybridomas. The productivity of hybridomas of the "Karel" series in
      tissue culture and in cultivation as ascitic fluid was evaluated. Among the
      antibodies analysed, all were specific to envelope proteins, of them 2 were
      against protein E2 and four against protein E1. Comparison of MCA biologic
      activity (neutralizing, antihemagglutinating activities, participation in
      immunofluorescence, EIA, and immune blotting) allows one to distinguish four
      different hybridomas among them producing specific antibodies differing in their
      properties.

PMID- 1979459
TI  - [Central presynaptic receptors].
AB  - Experiments on two different inhibitory presynaptic receptor systems are
      presented. 1. Superfused and electrically stimulated brain slices are a widely
      used experimental model to study the release of noradrenaline and its modulation
      by inhibitory alpha-2 adrenoceptors. By using a minisuperfusion chamber we
      succeeded in studying the simplest case of autoinhibition, i.e. the release of
      transmitter induced by a single pulse and two consecutive pulses, respectively.
      When electrical stimulation is performed using a single pulse, no autoinhibition
      is possible, whereas following stimulation with two pulses the transmitter
      released by the first pulse will inhibit the effect of the second pulse. By
      systemically varying the time interval between the two pulses the minimal time
      requirement for development of autoinhibition was determined to be 100 ms. Short
      pulse trains of high frequency such as 4 pulses within 30 ms circumvent
      autoinhibition and cause inhibition-free release by each applied pulse. The
      release of transmitter evoked in this way is not only free from autoinhibition
      but, in addition, easily measurable, which makes this method of stimulation very
      suitable for analyses at presynaptic receptors. By using this approach it became
      possible, for the first time, to determine dissociation constants of antagonists
      and agonists at the central presynaptic alpha-2 adrenoceptor without the
      distortion introduced by autoinhibition occurring during release. 2. There is a
      substantial body of evidence for a role of medullary serotonergic nerve cells in
      the regulation of blood pressure and heart rate. It is hypothesized that the
      serotonergic neurons project to the thoracic spinal cord exerting a tonic
      excitatory influence on presynaptic sympathetic neurons of the intermediolateral
      cell column. Experiments were performed in pentobarbital anaesthetized rats to
      reduce this excitatory tone by activating inhibitory autoreceptors which are
      located on the perikarya and dendrites on the serotonergic cells and which have
      been shown to belong to the 5-HT1A subtype. Local stereotactic injection of the 5
      HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) caused a decrease
      in mean arterial blood pressure (MAP) and heart rate (HR). The effects were
      blocked by pretreatment of the animals with the 5-HT1A antagonist spiroxatrine.
      Moreover, neurochemical lesioning of serotonergic neurons by intracisternal
      injection of the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) abolished the
      effects of 8-OH-DPAT. Bilateral intraspinal injection of 5,7-DHT, which
      interrupts the medullo-spinal serotonergic pathway, markedly attenuated the
      effects of local intramedullary injection of 8-OH-DPAT.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 1979460
TI  - [Anti-somatostatin autoantibodies in the blood serum of patients with
      schizophrenia].
AB  - Solid-phase IEA was used to measure the level of autoantibodies to somatostatin
      in the blood serum of 44 schizophrenics and 24 healthy donors. The patients
      suffering from schizophrenia manifested a higher (p less than 0.01) level of
      immune responsiveness of the blood serum to somatostatin (0.665 +/- 0.03) as
      compared to the control group (0.509 +/- 0.05). The main contribution to the
      differences between the groups as regards the parameter measured is made by
      patients with malignant (0.810 +/- 0.10) and paranoid (0.773 +/- 0.08)
      schizophrenia whereas the patients' subgroup with slow-progressive schizophrenia
      did not differ from normal regarding the level of autoantibodies to somatostatin
      in the serum (0.504 +/- 0.03). These tentative data agree with a hypothesis of
      the involvement of autoimmune processes into the development of schizophrenia.

PMID- 1979461
TI  - [T- and B-lymphocytes and their clinico-pathogenetic significance in patients
      with paranoid schizophrenia].
AB  - As many as 43 patients with first diagnosed paranoid schizophrenia running a
      shift-like course were examined for the blood counts of T and B lymphocytes with
      regard to the treatment conducted and disease standing. The patients received 3
      types of the treatment: insulin, neuroleptics and combined treatment (insulin
      plus neuroleptics). During the treatment and after it, the content of B
      lymphocytes remained practically unchanged (p greater than 0.05) in all the
      patients. The content of T lymphocytes was reduced throughout the whole period of
      affliction with schizophrenia. However, during the combined treatment of the
      disease, a tendency towards increase of T cells was revealed, which coincided
      with the best clinical indicators.

PMID- 1979462
TI  - [Comparative effectiveness of various methods of the treatment of patients with
      attack-like schizophrenia with depressive episodes].
AB  - The clinico-epidemiological method was used to examine the patients' population
      suffering from attack-like schizophrenia with a disease standing of 25 and more
      years. There were altogether 245 persons. Depressive attacks of the endogenous
      type were revealed in 1/3 of the patients, amounting to 153 attacks in total. Of
      these, 76.5% occurred at the disease onset, namely from the first to the fifth
      attack. A comparative all-round study was made of the efficacy of neuroleptics,
      antidepressants and combined therapy of neuroleptics and antidepressants, insulin
      coma ++ therapy and symptomatic remedies bearing in mind such criteria as the
      rate of attack removal, remission duration and quality, the character of the
      maintenance therapy. It has been established that the use of
      psychopharmacotherapy removes a depressive attack of the endogenous type more
      swiftly but long and stable remissions are only ensured by antidepressants.

PMID- 1979463
TI  - [Clinical and economic approach to evaluation of the effectiveness of moditen
      depot and haloperidol decanoate in the maintenance therapy of attack-like
      schizophrenia].
AB  - The efficacy of the use of moditen-depo and haloperidol decanoate as preventive
      anti-recurrence+ therapy was studied and compared in 2 groups of patients
      suffering from attack-like schizophrenia with frequent exacerbations. The cost
      use analysis made it possible to establish their higher efficacy as compared to
      the routine maintenance therapy. Proceeding from the clinical, economic and
      socioeconomic indicators the use of haloperidol decanoate turned out more
      effective than the use of moditen-depo.

PMID- 1979464
TI  - Effects of oxytocin upon the endocrine pancreas secretion and glucose turnover in
      normal man.
AB  - In normal man oxytocin infusion under basal conditions and at pharmacological
      doses evoked a rapid surge in plasma glucose and glucagon levels followed by a
      later increase in plasma insulin levels. Simultaneous [D-3H]glucose infusion
      indicated that oxytocin also produced a prompt and significant increase in
      hepatic glucose output with a secondary increase in glucose disappearance rate.
      Eight healthy volunteers were studied during euglycemic glucose clamp and
      simultaneous [D-3H]glucose infusion, during suppression of endogenous pancreatic
      secretion by cyclic somatostatin (250 micrograms/h) and during exogenous glucagon
      (67 ng/min) and insulin (0.15 mU.kg-1.min-1 from 0 to 120 min and 0.40 mU.kg
      1.min-1 from 121 to 240 min) replacement. During the first 60 min oxytocin (0.2
      U/min) evoked a transient but significant increase in plasma glucose levels and
      hepatic glucose output with a simultaneous suppression of the glucose infusion
      rate. No difference in glucose disappearance and metabolic clearance rates were
      recorded throughout the clamp irrespective of whether oxytocin was infused or
      not. So we conclude that oxytocin exerts a hyperglycemic effect through an A-cell
      stimulation and a glycogenolytic action.

PMID- 1979465
TI  - Inhibition by immunoglobulin G of synthesis of thyroid hormone in thyroid
      cultures from hypothyroid patients with goitrous Hashimoto's thyroiditis.
AB  - Recently, thyroid microsomal antigen was identified as thyroid peroxidase, and
      thyroid microsomal antibody was found to inhibit thyroid peroxidase activity in
      vitro. We investigated the possibility that anti-microsomal antibody inhibits the
      iodination of tyrosine, in vivo. Immunoglobulin G with or without anti-microsomal
      antibody from hypothyroid patients with goitrous Hashimoto's thyroiditis
      inhibited thyroid hormone synthesis in cultured slices of normal human thyroid
      tissue. IgGs with anti-microsomal antibody inhibited 125I thyroidal uptake and
      thyroid hormone synthesis stimulated by TSH more than normal IgG did. However,
      the same results were obtained with IgGs without anti-microsomal antibody. This
      effect did not involve anti-microsomal antibody, anti-thyroglobulin antibody, TSH
      binding inhibitor immunoglobulin, thyroid stimulation-blocking immunoglobulin, or
      the cAMP level of the thyroid tissue. The ratio of organic I to inorganic I with
      stimulation by TSH in slices incubated with IgG from hypothyroid patients with
      goitrous Hashimoto's thyroiditis or normal IgG was not significantly different,
      but was significantly higher in slices incubated with methylmercaptoimidazole.
      Therefore, IgG from hypothyroid patients with goitrous Hashimoto's thyroiditis
      mainly suppressed 125I thyroidal uptake, rather than inhibiting thyroid
      peroxidase activity. In addition, this IgG was present in the serum of 11 of the
      12 hypothyroid patients with Hashimoto's thyroiditis studied. This IgG may be
      involved in the mechanism that causes hypothyroidism in some patients with
      goitrous Hashimoto's disease.

PMID- 1979468
TI  - Proteinuria. Proceedings of the 2nd Roma Nephrology Conference. Fiuggi, September
      22-23, 1989.

PMID- 1979466
TI  - The effect of pre-operative potassium iodide therapy on antibody production.
AB  - Previous studies have suggested that iodide may increase the incidence of thyroid
      disease and anti-thyroid antibodies in predisposed individuals. This study has
      considered the effects of pre-operative potassium iodide (60 mg twice daily, for
      10 days) on the immune system of patients with Graves' disease. The treatment
      regimen used maintained all patients in a clinically and biochemically euthyroid
      state prior to surgery. Potassium iodide significantly increased serum
      thyrotropin receptor antibody levels and B cell activity as determined by
      increased immunoglobulin production from mitogen stimulated peripheral blood
      lymphocytes. These effects were not observed in the two control groups of Graves'
      disease patients. Our in vivo findings would support previous in vitro work
      showing that potassium iodide does act on the immune system and this may be the
      mechanism by which iodide induces thyroid dysfunction in predisposed individuals.

PMID- 1979467
TI  - A symposium: Atherosclerosis and vascular protection. March 16-17, 1990, New
      Orleans, Louisiana. Proceedings.

PMID- 1979469
TI  - Pharmacokinetics of oral contraceptive steroids and drug interactions. A
      symposium. Salzburg, Austria, September 14-16, 1989. Proceedings.

PMID- 1979470
TI  - Treatment of asthma and allergic rhinitis during pregnancy.

PMID- 1979471
TI  - Comparison of cetirizine and terfenadine in the treatment of chronic idiopathic
      urticaria.

PMID- 1979472
TI  - Evaluation of the effect of oral cetirizine on antigen-induced immediate
      asthmatic response.

PMID- 1979474
TI  - Pharmacologic modulation of allergic cutaneous inflammation.

PMID- 1979473
TI  - Double-blind multicenter study of cetirizine in grass-pollen-induced asthma.

PMID- 1979475
TI  - Cetirizine effects on the cutaneous allergic reaction in humans.

PMID- 1979476
TI  - Therapeutic effects of cetirizine in delayed pressure urticaria. Part 1. Effects
      on weight tests and skin-window cytology.

PMID- 1979478
TI  - [Hypertension in Takayasu's disease].

PMID- 1979477
TI  - Cetirizine inhibits delayed pressure urticaria. Part 2. Skin biopsy findings.

PMID- 1979479
TI  - [Pleuropulmonary manifestations of rheumatoid arthritis].

PMID- 1979480
TI  - [Primary prevention of digestive hemorrhages in cirrhotic patients].

PMID- 1979481
TI  - Abnormal function of CD4+ helper/inducer T lymphocytes in a patient with
      widespread human papillomavirus type 3-related infection.
AB  - Human papillomavirus-induced infections may be associated with cellular
      immunodeficiency. However, very little is known about the dysfunctional
      interactions among T lymphocytes, B lymphocytes, and antigen-presenting cells. A
      30-year-old heterosexual man with a 10-year history of persistent multiple
      refractory flat wart lesions containing human papillomavirus type 3-related DNA
      sequence was studied. The patient had a severe depletion of CD4+ T lymphocytes
      and a compensatory increase in the number of CD8+ T lymphocytes. Impaired T
      lymphocyte response to various stimuli was found. Depletion of the increased
      number of CD8+ T lymphocytes, which suppressed immunoglobulin production in
      vitro, did not restore the impaired T-lymphocyte response. Immobilized anti-CD3
      beads that stimulate the T lymphocyte antigen complex in the absence of antigen
      presenting cells indicated a T-lymphocyte defect, rather than a decreased antigen
      presenting cell function. Thus, the pronounced cellular immunodeficiency was due
      to abnormal function of the CD4+ helper/inducer T lymphocytes.

PMID- 1979482
TI  - [14th Brazilian Congress of Neurology. Rio de Janeiro, September 22-27, 1990.
      Proceedings].

PMID- 1979483
TI  - Medical management of phaeochromocytoma in pregnancy.

PMID- 1979484
TI  - Transvection and long-distance gene regulation.
AB  - Numerous genes contain regulatory elements located many tens of kilobases away
      from the promoter they control. Specific mechanisms must be required to ensure
      that such distant elements can find and interact with their proper targets but
      not with extraneous genes. This review explores the connections between
      transvection phenomena, the activation of domains of homeotic gene expression,
      position effect variegation and silencers. These various examples of long
      distance effects suggest that, in all cases, related forms of chromatin packaging
      may be involved.

PMID- 1979486
TI  - Metaphors and the role of genes in development.
AB  - In describing the flawless regularity of developmental processes and the
      correlation between changes at certain genetic loci and changes in morphology,
      biologists frequently employ two metaphors: that genes 'control' development, and
      that genomes embody 'programs' for development. Although these metaphors have an
      admirable sharpness and punch, they lead, when taken literally, to highly
      distorted pictures of developmental processes. A more balanced, and useful, view
      of the role of genes in development is that they act as suppliers of the material
      needs of development and, in some instances, as context-dependent catalysts of
      cellular changes, rather than as 'controllers' of developmental progress and
      direction. The consequences of adopting this alternative view of development are
      discussed.

PMID- 1979485
TI  - Retinoic acid: the morphogen of the main body axis?

PMID- 1979487
TI  - Differential expression of the murine and rat renin genes in peripheral
      subcutaneous tissue.
AB  - We have previously identified peripheral subcutaneous tissue as a bonafide site
      of primary renin expression in the mouse fetus by virtue of oncogene mediated
      tumorigenesis in transgenic mice. In this report we demonstrate that the murine
      renin genes are differentially expressed in this tissue. Through selective
      breeding and differential primer extension we demonstrate that Ren-1d and Ren-1c
      transcripts were several fold more abundant than Ren-2. Renin transcripts were
      also identified in fetal subcutaneous tissues of Spontaneously Hypertensive (SHR)
      and Wistar Kyoto (WKY) rats. We conclude from these studies that expression of
      renin during fetal development may be widespread in rodents with its temporal and
      spatial localization consistent with a role in fetal development.

PMID- 1979488
TI  - Rat follistatin: gonadal and extragonadal expression and evidence for alternative
      splicing.
AB  - Follistatin (FS) or FSH-suppressing protein is a polypeptide which exists in
      multiple forms and has inhibin-like activity. We investigated the distribution of
      tissues expressing FS mRNA. A segment of the rat FS mRNA corresponding to the
      last 157 nucleotides of exon 5 and the first 71 nucleotides of exon 6 was
      prepared by PCR and subcloned in plasmid GEM4Z (pGEM4Z) to produce a radiolabeled
      RNA probe. S1-Nuclease analysis of RNA extracted from rat tissues indicated
      alternative splicing of the rat FS gene and gonadal as well as extragonadal
      expression. In addition to the ovary and testis, the FS mRNA was detected in
      cerebral cortex, pituitary, adrenal, thymus, pancreas, gut, kidney, heart,
      uterus, skeletal muscle and lung. Treatment of female rats with combined Pregnant
      Mare Serum Gonadotropin (PMSG) and human Chorionic Gonadotropin (hCG) increased
      expression of FS mRNA in the ovary. Our results show that the mRNA for the
      precursor of the larger known form of FS (FS 344) is much more abundant than the
      mRNA for the smaller molecule (less than 5%) and that stimulation of FS
      transcription by PMSG and hCG in the ovary does not change this relationship.

PMID- 1979489
TI  - H(+)-ATPase, a primary pump for accumulation of neurotransmitters, is a major
      constituent of brain synaptic vesicles.
AB  - Upon treatment with sodium carbonate, rat brain synaptic vesicles lost ATP
      dependent H+ transport and released major polypeptide components (about 72, 57,
      41, 34 and 33 kDa). These polypeptides, consisting about 15% of the total
      protein, were identified as subunits of H(+)-ATPase by immunoblotting with
      antibodies against H(+)-ATPase from chromaffin granules. The same treatment also
      abolished the ATP-dependent, bafilomycin-sensitive uptakes of glutamate,
      serotonin and gamma-aminobutyrate by the synaptic vesicles. These results
      indicated that H(+)-ATPase is a major constituent of the vesicles (consisting
      about 20% of their total protein) and is a primary pump for accumulation of
      neurotransmitters.

PMID- 1979490
TI  - Pest sequences present in the subunits of phosphorylase kinase.
AB  - We report that the amino acid sequences of all four subunits of rabbit skeletal
      muscle phosphorylase kinase possess one or more regions rich in proline (P),
      glutamic acid (E), serine (S) and threonine (T). alpha and beta subunits contain
      strong PEST sequences, showing PEST scores greater than 0 (Rogers et al. (1986)
      Science 234, 364-368), while gamma and delta subunits contain weak PEST regions
      (negative PEST scores greater than -5.3). In addition to PEST sequences, alpha,
      beta and gamma subunits contain clusters of arginine pairs. The above sequence
      characteristics may serve to signal rapid turnover of phosphorylase kinase.

PMID- 1979491
TI  - Direct and indirect modulation of neuronal calcium currents by G-protein
      activation.
AB  - Evidence is presented for modulation of the various components of neuronal Ca2+
      currents by G-proteins and by gamma-aminobutyric acid B (GABAB) receptor
      activation. The mechanism of these interactions and the possible involvement of
      second messengers is discussed. The role of inhibition of Ca2+ channels in
      presynaptic inhibition of neurotransmitter release is examined.

PMID- 1979492
TI  - Changes in striatal cholinergic, gabaergic, dopaminergic and serotoninergic
      biochemical markers after kainic acid-induced thalamic lesions in the rat.
AB  - Kinetic parameters of 3H-choline, 3H-GABA and 3H-dopamine (DA) uptakes in
      striatal homogenates containing nerve endings were determined 2 to 3 weeks after
      kainic acid injection into the ipsilateral "centre median"-parafascicular complex
      area of the thalamus in the rat. Results showed a marked decrease in 3H-choline
      uptake concomitant with a selective decrease in Vmax. Data also showed a large
      decrease in 3H-GABA uptake resulting from a decreased affinity of uptake sites
      for their substrate. These data were associated with the previously described
      decrease in choline acetyltransferase and increase in glutamic acid decarboxylase
      apparent activity, respectively. An apparent marked increase in 3H-DA uptake was
      likewise measured, mainly related to an increase in Vmax. Determination of
      serotonin (5HT) and 5-hydroxyindole acetic acid (5HIAA) endogenous contents
      showed in the deafferented striatum a decrease in 5HT concentrations associated
      with an increase in 5HIAA levels. Taken together, all these changes in
      neurotransmitter markers suggest that, directly through the thalamostriatal
      pathway or indirectly, the thalamus can exert a complex influence on striatal
      cholinergic and GABAergic neuronal functions as well as on the activity of
      dopaminergic and serotoninergic striatal afferent fibers.

PMID- 1979493
TI  - Comparative analysis of the fragments of highly repeated DNA of Homo, Pan, Macaca
      and Cercopithecus.
AB  - In the present paper the restriction patterns of Homo, Pan troglodytes, Macaca
      fascicularis and Cercopithecus aethiops, obtained by digestion with Eco RI
      endonuclease, were compared. All these species showed two common bands at 0.3 and
      0.6 Kb. In this region another band at 0.5 Kb was present in Macaca fascicularis
      and Cercopithecus aethiops. Furthermore Macaca fascicularis, Cercopithecus
      aethiops and Pan troglodytes showed a series of bands not present in humans. The
      distance matrix shows a strong similarity between Homo and Pan and a decreasing
      similarity with Macaca fascicularis and Cercopithecus aethiops. No intraspecific
      variability was observed.

PMID- 1979494
TI  - [Electric stimulation of the dental pulp in the evaluation of the central effect
      of analgesics].
AB  - We conducted a double-blind cross-over study in ten volunteers aged from 19 to 30
      years, to compare the pain control effects of a single oral dose of two analgesic
      compounds (drug A: propyphenazone mg 250, ethylmorphine mg 5, caffeine mg 5; drug
      B: dipyrone mg 500, diphenhydramine mg 12.5, adiphenine mg 5, ethyl aminobenzoate
      mg 2.5) in an experimental pain model using stimulation of dental pulp. Constant
      voltage stimuli were delivered through silver chloride electrodes placed in
      contact with the vestibular surface of the upper medial incisor. At the beginning
      of the session, the pain input was graded by asking the subject to identify the
      weakest stimulus perceived (threshold level) and the strongest stimulus endurable
      (tolerance level). The range between threshold and tolerance level was divided in
      nine steps plus a subliminal step. The ten steps were delivered randomly, and
      each series of steps was repeated eight times. The subjects were instructed to
      rate the pain sensation in an arbitrary scale of 5 degrees. The procedure was
      repeated at 60 min and 180 min after drug administration. Each subject received
      two tablets of drug A or drug B in two different sessions at weekly intervals.
      Statistical analysis of the procedures showed that neither drug A nor drug B
      significantly affected the pain threshold. Drug A significantly reduced the total
      pain score (P less than 0.01) and its action peaked 60 min after
      administration.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1979495
TI  - Localization of insertion sites by bidirectional sequencing.

PMID- 1979496
TI  - A method for immunocytochemical identification of biocytin-labeled neurons
      following intracellular recording.
AB  - Because of the large number of cell phenotypes in the nervous system, it has been
      difficult to characterize each as to specific electrophysiological properties. We
      have developed a technique that allows the identification of central and
      peripheral nervous system neurons following intracellular recording. We use
      electrodes that contain 2% biocytin to do current- and voltage-clamp recordings;
      the recorded neurons are revealed with streptavidin-fluorescein isothiocyanate
      labeling and identified through immunohistochemical staining for specific
      antigens. Presently, we report on the use of this technique to identify four cell
      types--dopamine, beta-endorphin, vasopressin and oxytocin--in the hypothalamus of
      the mammal. This technique should have widespread applicability for
      electrophysiologists.

PMID- 1979497
TI  - Rat DARPP-32: cloning, sequencing, and characterization of the cDNA.
AB  - DARPP-32, a substrate for cyclic AMP-dependent protein kinase, is highly enriched
      in the caudate nucleus. In the present study, the cDNA for rat DARPP-32 was
      isolated and characterized. When compared to the coding region of bovine DARPP-32
      cDNA, there was 86% identity at the nucleotide level, and 84% identity at the
      amino acid level. The homology in the region previously noted to be similar to
      phosphatase inhibitor-1 remained intact. There were also 3'-untranslated regions
      that were highly conserved. The DARPP-32 mRNA, which appeared as a doublet, was
      widely distributed in the central nervous system and was highly enriched in the
      striatum. Southern blot analysis revealed a simple hybridization pattern,
      consistent with the presence of a single gene coding for rat DARPP-32. Unilateral
      destruction of the nigrostriatal dopaminergic pathway by injection of 6
      hydroxydopamine (6-OHDA) into the substantia nigra did not alter the striatal
      steady state levels of DARPP-32 mRNA.

PMID- 1979499
TI  - Neurotransmitter, opiodergic system, steroid-hormone interaction and involvement
      in the replacement therapy of sexual disorders.
AB  - Dopamine (DA) and serotonin (5-HT) are the neurotransmitters most directly
      involved in sexual activity. DA plays a stimulatory role while 5-HT has an
      inhibitory effect. The two monoaminergic systems modulate the secretion of many
      hormones (GnRH, LH, testosterone, prolactin and endorphins) involved in sexual
      functional capacity. Furthermore, hormones influence synthesis and storage of
      brain neurotransmitters. Impotence can often be associated to clinical depression
      and altered neurotransmitter function. Moreover, stress represents an unbalance
      between various neurotransmitter systems and can induce impotence especially when
      disorders of the endorphinic system are present. Replacement therapy is based
      upon the understanding of these basic concepts. Impotence due to an underlying
      depressive illness must be treated with dopaminergic antidepressant drugs; while
      in stressful conditions a good response to the naloxone test is the preliminary
      criterion to subsequent naltrexone treatment. When a hormonal deficiency has been
      proved, the hormone replacement therapy is of course highly effective
      (gonadotropins in hypogonadotropic syndromes, testosterone in aging, etc.).
      Finally, idiopathic impotence could be treated by DA agonist and/or 5-HT
      antagonist drugs either alone or better yet in association with psychotherapy.

PMID- 1979498
TI  - Developmental expression of mRNAs encoding thymosins beta 4 and beta 10 in rat
      brain and other tissues.
AB  - In the course of screening a fetal rat cerebellum cDNA library for
      developmentally regulated sequences, we have identified a cDNA clone identical in
      sequence to that encoding a protein originally isolated from thymus, thymosin
      beta 10. Based on northern hybridization analyses with gene-specific
      oligonucleotide probes derived from the 3'-untranslated regions of thymosin beta
      10 mRNA and the closely related beta 4 mRNA, we showed that both thymosin mRNAs
      were present at highest levels in fetal cortex and cerebellum but also were
      present at varying levels in all other fetal tissues examined (thymus, spleen,
      lung, kidney, adrenal, heart, and liver). Steady-state levels of thymosin beta 10
      mRNA in cerebellum declined to negligible levels after day 14 of postnatal
      development. Its levels exhibited a similar pattern in developing cortex,
      although the adult cortex had slightly higher thymosin beta 10 mRNA levels. These
      results suggest that thymosin beta 10 mRNA is subject to strong developmental
      regulation in the rat central nervous system. Reduction of thymosin beta 10 mRNA
      levels also was seen during development of kidney, heart, and liver. Levels of
      both thymosin beta 10 and beta 4 mRNAs remained relatively constant during
      development of thymus, spleen, and lung. Thymosin beta 4 mRNA levels dropped much
      less sharply during brain development than did levels of the beta 10 mRNA. Testis
      and ovary contained the highest relative levels of thymosin beta 10 mRNA among
      adult tissues, but little thymosin beta 4 mRNA. A novel thymosin beta 10 mRNA
      species unique to adult testis was detected. These results indicate that both
      thymosins must function in the development of brain and many other organs, as
      well as in different subsets of organs in the adult.

PMID- 1979500
TI  - Pharmacological characterization of tardive akathisia.
AB  - A patient with tardive neuroleptic-induced akathisia was investigated with
      multiple pharmacological challenges. It was noted that the patient responded
      positively to benztropine, bromocriptine, and propranolol, and negatively to
      physostigmine, and showed little or no response to discontinuation of
      neuroleptics and challenges with metoclopramide, metoprolol, atenolol, and
      clonidine. The implications of this pharmacological characterization for the
      understanding of the pathophysiology of tardive akathisia in relation to acute
      akathisia and tardive dyskinesia are discussed.

PMID- 1979501
TI  - A frameshift mutation leading to type 1 antithrombin deficiency and thrombosis.
AB  - Type 1 antithrombin III (ATIII) deficiency, which is the commonest form of
      inherited ATIII defect, is characterized by a quantitative reduction in both
      immunologically and functionally detectable protein. This condition is associated
      with a high incidence of thromboembolic disorder. Previous investigations have
      shown that the ATIII genes in the majority of cases are grossly intact, but the
      precise underlying molecular defects remain unknown. We have investigated the
      molecular basis of a type 1 ATIII deficiency in an Italian kindred by enzymatic
      amplification of the ATIII gene sequences in affected family members and direct
      sequencing of the amplified genomic DNA. A novel mutation, the deletion of a
      single T in the second position of codon 119, was identified in each of the
      affected individuals. The resulting frameshift leads to a premature termination
      in codon 126, effectively resulting in a null allele.

PMID- 1979503
TI  - Address by Dr. Hiroshi Nakajima.

PMID- 1979502
TI  - The molecular genetic analysis of hemophilia A: a directed search strategy for
      the detection of point mutations in the human factor VIII gene.
AB  - A directed-search strategy for point mutations in the factor VIII gene causing
      hemophilia A was used to screen eight potentially hypermutable CpG dinucleotides
      occurring at sites deemed to be of functional importance. Polymerase chain
      reaction-amplified DNA samples from 793 unrelated individuals with hemophilia A
      were screened by discriminant oligonucleotide hybridization. Point mutations were
      identified in 16 patients that were consistent with a model of 5-methylcytosine
      (5mC) deamination. Four new examples of recurrent mutation were demonstrated at
      the following codons: 336 (CGA----TGA), 372 (CGC----TGC), 372 (CGC----CAC), and
      1689 (CGC----TGC). These are functionally important cleavage sites for either
      activated protein C or thrombin. Further novel C----T transitions were identified
      in the remaining arginine codons screened (-5, 427, 583, 795, and 1696),
      resulting in the creation of TGA termination codons. Differences in mutation
      frequency were found both within and between the CpG sites and between ethnic
      groups. These differences are assumed to be due to differences in the level of
      cytosine methylation at these sites, although direct evidence for this inference
      is lacking.

PMID- 1979504
TI  - The last fight against tuberculosis until elimination, a workshop/course of the
      IUATLD-Europe Region and WHO. Opening addresses.

PMID- 1979505
TI  - Resolutions taken at the World Conference on Lung Health, Boston 1990.

PMID- 1979506
TI  - Effects of morphine, H-Tyr-D-Arg-Phe-Lys-NH2 (DALDA) and B-HT920 on non
      cholinergic nerve-mediated bronchoconstriction in pithed guinea-pigs.
AB  - 1. Electrical stimulation (1 ms, 5 Hz, 80 V) for 5 or 15 s at the level of C4-T1
      in the spinal canal of artificially respired pithed guinea-pigs (which had
      received intravenously (i.v.) (+)-tubocurarine chloride 2 mg kg-1, atropine
      sulphate 2 mg kg-1 and pentolinium tartrate 5 mg kg-1) caused constriction of
      airways, indicated by increased insufflation pressure. 2. This non-cholinergic
      constriction was inhibited by morphine (1-3 mg kg-1, i.v.), the peripherally
      acting mu-receptor agonist, H-Tyr-D-Arg-Phe-Lys-NH2 (DALDA, 0.1-1 mg kg-1, i.v.)
      or the alpha 2-adrenoceptor agonist B-HT920 (1-3 mg kg-1, i.v.). 3. The effects
      of either morphine (3 mg kg-1, i.v.) or DALDA (1 mg kg-1, i.v.) were inhibited by
      naloxone (3 mg kg-1, i.v.). Idazoxan (3 mg kg-1, i.v.) inhibited the anti
      constrictor effect of B-HT920 (3 mg kg-1, i.v.), but not that of DALDA (0.1 mg kg
      1, i.v.). 4. Thus activation of peripheral mu-opioid receptors or alpha 2
      adrenoceptors inhibits airways constriction induced by non-cholinergic nerve
      stimulation in the pithed guinea-pig. This preparation therefore provides a
      further method for the in vivo examination of the effects of drugs on non
      cholinergic tracheobronchial constrictor nerve function.

PMID- 1979507
TI  - Functional evidence for heterogeneity of peripheral prejunctional alpha 2
      adrenoceptors.
AB  - 1. We have examined the potencies of a series of alpha 2-adrenoceptor antagonists
      in functional studies of prejunctional alpha 2-adrenoceptors in rat atrium and
      vas deferens, and compared potencies with affinities for the alpha 2A-ligand
      binding site of human platelet and the alpha 2B-site of rat kidney. 2. Antagonist
      potency in rat atrium was expressed as an EC30 (concentration producing 30%
      increase in the stimulation-evoked overflow of tritium in tissues pre-incubated
      with [3H]-noradrenaline). Antagonist potency in rat vas deferens was expressed as
      a pA2 or KB at antagonizing the inhibition by the alpha 2-adrenoceptor agonist
      xylazine of the isometric twitch to a single stimulus, or as an EC30. 3. In
      ligand binding studies, Ki values were obtained for the displacement by alpha
      adrenoceptor antagonists of [3H]-yohimbine binding to human platelet or rat
      kidney membranes. 4. In functional studies, three antagonists (ARC 239, prazosin
      and chlorpromazine) distinguished between prejunctional alpha 2-adrenoceptors of
      rat atrium (EC30) and rat vas deferens (pA2) and showed 49, 12 and 7 times higher
      potency in rat atrium, respectively. ARC 239 was also 17 times more potent in rat
      atrium than rat vas deferens when EC30 values were compared. 5. The correlation
      of affinity for the alpha 2A-site of human platelet was better with prejunctional
      potency in rat vas deferens than rat atrium. 6. The correlation of affinity for
      the alpha 2B-site of rat kidney was better with prejunctional potency in rat
      atrium than rat vas deferens. 7. It is concluded that prejunctional alpha 2
      adrenoceptors of rat vas deferens and rat atrium differ, and these receptors may
      resemble the alpha 2A- and alpha 2B-ligand binding sites, respectively.

PMID- 1979508
TI  - Adrenalectomy abolishes antagonism of alpha-adrenoceptor-mediated hypotension by
      a beta-blocker in conscious rats.
AB  - 1. The effects of a single bolus injection of propranolol, atenolol or ICI
      118,551, non-selective beta-, selective beta 1- and selective beta 2-adrenoceptor
      antagonists, respectively, on mean arterial pressure (MAP) and plasma
      catecholamine concentrations were examined in seven groups of conscious and
      unrestrained adrenalectomized rats receiving a continuous infusion of the alpha
      adrenoceptor antagonist phentolamine. In all rats adrenaline was undetectable in
      the plasma four days after adrenalectomy. 2. In the first three groups,
      phentolamine significantly decreased MAP and increased the plasma concentrations
      of noradrenaline. The injection of propranolol, atenolol or ICI 118,551 in Groups
      I, II and III, respectively, caused a small increase in MAP and a small, but not
      significant, decrease in plasma noradrenaline concentrations. 3. Groups IV, V and
      VI were given a continuous infusion of adrenaline for 1 h prior to the infusion
      of phentolamine, followed by a bolus injection of propranolol, atenolol or ICI
      118,551, respectively. Group VII was treated similarly to IV, but was also given
      daily cortisone replacement after adrenalectomy. Adrenaline slightly, but not
      significantly, decreased MAP while phentolamine significantly decreased MAP and
      increased plasma noradrenaline concentrations in all groups. A subsequent
      injection of a beta-blocker caused a significant increase in MAP in each group
      and a slight decrease in the plasma level of noradrenaline which reached
      statistical significance in group VII. The pressor effect of propranolol was
      significantly greater in the cortisone-treated rats (Group VII) than in Group IV.
      5. The results suggest that adrenaline and adrenocortical steroids are both
      involved in the antagonism of alpha-adrenoceptor-induced hypotension by a beta
      blocker.

PMID- 1979509
TI  - Chronic beta 1-adrenoceptor antagonist treatment sensitizes beta 2-adrenoceptors,
      but desensitizes M2-muscarinic receptors in the human right atrium.
AB  - 1. In 64 patients undergoing coronary artery bypass grafting the effects of
      chronic beta 1-adrenoceptor antagonist (metoprolol, atenolol, bisoprolol)
      treatment on right atrial beta-adrenoceptor and muscarinic M2-receptor number and
      functional responsiveness were investigated. 2. The beta 1-adrenoceptor
      antagonists increased right atrial beta 1-adrenoceptor number, did not affect
      beta 2-adrenoceptor number, and decreased muscarinic M2-receptor number. 3.
      Concomitantly, activation of right atrial adenylate cyclase by 10 microM GTP, 10
      microM isoprenaline and 1 microM forskolin was enhanced and inhibition by 100
      microM carbachol was diminished. 4. On isolated, electrically driven right atria
      the beta 1-adrenoceptor-mediated positive inotropic effect of noradrenaline was -
      even with beta 1-adrenoceptor number increased - not altered, while the beta 2
      adrenoceptor-mediated effect of procaterol was markedly enhanced. However, the
      carbachol-induced negative inotropic effect was decreased. 5. It is concluded
      that chronic beta 1-adrenoceptor antagonist treatment increases beta 1
      adrenoceptor number and concomitantly sensitizes beta 2-adrenoceptor function,
      but desensitizes muscarinic M2-receptor function in the human heart.

PMID- 1979510
TI  - The effectiveness of alpha 2-adrenoceptor activation increases from the distal to
      the proximal part of the veins of canine limbs.
AB  - 1. The effectiveness of alpha 1- and alpha 2-adrenoceptor activation was compared
      at different levels of the saphenous and cephalic vein of the dog in vitro. 2.
      Helically cut strips were used to determine concentration-response curves to
      phenylephrine, noradrenaline, UK-14,304 (5-bromo-6-(imidazoline-2-ylamino)
      quinoxaline) and B-HT 920 (2-amino-6-allyl-5,6,7,8-tetra-hydro-4H-(thiazo)-4,5-d
      azepine). The effect of prazosin and yohimbine on these curves was also studied.
      3. At the distal level, the maximum response to UK-14,304 amounted to 33 and 50%
      of those to noradrenaline in the saphenous and cephalic vein, respectively, while
      at the proximal level the maximum response to UK-14,304 amounted to 72 and 78% of
      those to noradrenaline, in the saphenous and cephalic vein, respectively. 4. In
      both vessels, the results obtained with B-HT 920 were very similar to those for
      UK-14,304. 5. The pD2 values for UK-14,304 - which were identical at the three
      levels of both vessels - and the pA2 values for the antagonism exerted by either
      prazosin or yohimbine against the responses to UK-14,304 indicate that the alpha
      2-adrenoceptors are identical at the different levels of both vessels. 6. These
      results show that the effectiveness of alpha 2-adrenoceptor stimulation increases
      from the distal to the proximal regions of canine limb veins. Apparently, this is
      due to a greater density of alpha 2-adrenoceptors in the proximal regions. 7.
      Yohimbine is much more potent against phenylephrine distally than proximally in
      both vessels. However, after 30 nm phenoxybenzamine - a concentration which
      eliminates the vast majority of alpha,-adrenoceptors without affecting alpha 2
      adrenoceptors - yohimbine became equally potent at both levels, suggesting that
      the difference existing before phenoxybenzamine depended on alpha,-adrenoceptors.
      Hence it is concluded that alpha,-adrenoceptors in distal and proximal portions
      may differ.

PMID- 1979511
TI  - Inhibition of nicotine-induced relaxation of the bovine retractor penis muscle by
      compounds known to have ganglion-blocking properties.
AB  - 1. The relative potency in blocking the nicotine-induced relaxation of the bovine
      retractor penis muscle (BRP) was estimated for 12 drugs known to have ganglion
      blocking properties. 2. The order of potency of the drugs studied was
      mecamylamine greater than chlorisondamine greater than pentolinium greater than
      propantheline greater than (+)-tubocurarine greater than hexamethonium greater
      than emepronium greater than tetraethylammonium greater than glycopyrrolate
      greater than decamethonium greater than butylscopolamine greater than
      scopolamine. 3. The results conform well to those obtained with other
      pharmacological methods used for the estimation of ganglion-blocking activity. 4.
      It is concluded that blockade of the nicotinic relaxation of the BRP can be used
      as an alternative method for quantitative assessment of ganglion-blocking
      activity. 5. Advantages of this technique are that it discriminates well between
      antinicotinic and antimuscarinic activity and that it satisfies most or all
      ethical and economical demands. 6. It is also possible that this method has
      certain value in predicting whether a drug has enough ganglion-blocking activity
      to be likely to cause impotence.

PMID- 1979512
TI  - The anti-adrenergic effect of adenosine and its blockade by pertussis toxin: a
      comparative study in myocytes isolated from guinea-pig, rat and failing human
      hearts.
AB  - 1. In intact ventricular preparation, adenosine has been shown to reduce the beta
      adrenoceptor-induced increase in contraction (the anti-adrenergic effect). In the
      present study we have investigated this effect of adenosine on isolated
      ventricular myocytes from failing human heart and normal guinea-pig and rat
      heart. 2. Adenosine in the absence of beta-adrenoceptor-mediated stimulation had
      no effect on contraction in human and guinea-pig myocytes but produced a variable
      effect in rat myocytes. 3. 8-Cyclopentyl 1,3-dipropylxanthine (CPX), a selective
      A1-receptor antagonist, antagonised the anti-adrenergic effect of adenosine in
      guinea-pig myocytes. 4. The anti-adrenergic effect of adenosine was greater in
      guinea-pig than rat myocytes and even more pronounced in cells isolated from
      failing human heart. 5. Pertussis toxin-pretreatment at 35 degrees C of guinea
      pig and human myocytes abolished the anti-adrenergic effect of adenosine. Longer
      exposure to higher concentrations of pertussis toxin was required for complete
      abolition in human compared to guinea-pig cells. 6. These results support the
      suggestion that the adenosine receptors mediating the anti-adrenergic effect of
      adenosine are of the A1 subtype and are coupled to the inhibitory guanine
      nucleotide binding protein, Gi/Go. 7. Pertussis toxin pretreatment increased the
      sensitivity of guinea-pig myocytes to isoprenaline in the absence of adenosine;
      the EC50 value was decreased by a factor of 10. This suggests that Gi may exert a
      tonic inhibitory effect on the beta-adrenoceptor/adenylate cyclase interaction in
      normal myocardium.

PMID- 1979514
TI  - Sulphasalazine treatment of psoriatic arthritis.

PMID- 1979513
TI  - Methylsulphasalazine in rheumatoid arthritis.
AB  - Methylsulphasalazine, which differs from sulphasalazine by the addition of one
      methyl group, may provide the benefits of the parent drug with fewer side-effects
      in rheumatoid arthritis (RA). We describe the outcome of its use in RA. Of 21
      patients entered into the study, 10 successfully completed 6 months of therapy;
      five developed adverse effects, four withdrew for reasons unrelated to drug
      treatment and two stopped because of inefficacy. No serious adverse effects were
      reported. A statistically significant improvement in most clinical assessments
      was observed from weeks 8-12 onwards. Significant improvement in plasma viscosity
      was observed and there was a trend towards improvement in serum CRP, histidine
      and IgM concentrations. There was a good correlation between mean serial changes
      in clinical and biochemical assessments indicating that the drug may exhibit the
      properties of a second-line agent. Median steady-state serum concentrations of
      methylsulphasalazine and methylsulphapyridine were 26.6 micrograms/ml and 2.85
      micrograms/ml respectively.

PMID- 1979515
TI  - CRF-like effects of sauvagine and urotensin I on synaptosomal tyrosine
      hydroxylase activity of mouse striatum.
AB  - In the present study we have investigated whether sauvagine (SVG) and urotensin I
      (UT), two peptides displaying sequence homology with corticotropin-releasing
      factor (CRF), could affect synaptosomal tyrosine hydroxylase (TH) activity of
      mouse striatum in a manner similar to CRF. The enzyme activity was assayed in
      supernatants obtained following sonication and centrifugation of homogenates
      preincubated with the peptides. SVG and UT produced a concentration-dependent
      increase of TH activity with a half-maximal effect obtained at 5 and 10 nM,
      respectively. SVG and UT were as effective as CRF with maximal stimulations
      corresponding to 52-58% increase of basal enzyme activity, whereas the rank order
      of potency was SVG greater than UT = CRF. Kinetic analysis of TH activity versus
      low concentrations of the pterin co-factor (0.05-0.4 mM) indicated that the
      stimulations elicited by CRF, SVG and UT were associated with an increase in the
      Vmax of the enzyme form with high affinity for the co-factor. The CRF receptor
      antagonist alpha-helical CRF9-41 inhibited the effects of all 3 peptides.
      Moreover, the combined addition of CRF with either SVG or UT did not produce
      additive effects on TH activity. The stimulatory effects of CRF, SVG and UT were
      dependent on the concentration of extracellular free Ca2+, being minimal in a
      Ca2(+)-free medium and maximal at about 0.5 mM extracellular free Ca2+. These
      results indicate that SVG and UT can mimic the effect of CRF on synaptosomal TH
      by acting on a common receptor site associated with a Ca2(+)-dependent mechanism.

PMID- 1979516
TI  - Similar post-lesion receptor readjustments following the unilateral 6
      hydroxydopamine lesion of the dopaminergic mesotelencephalic system in neonatal
      and adult rats.
AB  - The ascending dopaminergic system of adult or 3-day-old rats has been
      unilaterally lesioned by the intraparenchymal injection of 6-hydroxydopamine
      aimed at the medial forebrain bundle at the level of the lateral hypothalamus.
      Nigral dopaminergic neurons disappeared following the lesion on the lesioned side
      in both experimental groups while the depletion of the ventral tegmental area was
      less extensive, especially following the neonatal lesion. Striatal regions were
      markedly depleted of their dopaminergic innervation, although the magnitude of
      the depletion was slightly higher following the adult stage lesion as judged on
      the basis of biochemical measurements (99% vs. 96%). Amphetamine (5 mg/kg) evoked
      an identical ipsilateral rotational response in both experimental groups.
      Moreover, this rotational response was blocked both by the specific D1 receptor
      blocker SCH-23390 (0.1 mg/kg) and the specific D2 receptor antagonist raclopride
      (2 mg/kg). Likewise, contralateral rotational responses to the directly acting D1
      and D2 dopamine receptor agonists SKF-38393 (2.5 mg/kg) and LY-171555 (0.15
      mg/kg) were similar in both experimental groups, both qualitatively and
      quantitatively. These results confirm conclusions obtained in earlier works, and
      indicate that reported differences in behavioral deficits between animals
      lesioned as neonates or adults are not related to differing modifications of
      striatal DA receptor sensitivities.

PMID- 1979517
TI  - Effects of MDMA ('ecstasy') on firing rates of serotonergic, dopaminergic, and
      noradrenergic neurons in the rat.
AB  - 3,4-Methylenedioxymethamphetamine (MDMA), a non-hallucinogenic drug of abuse,
      potently depressed firing rates of a subpopulation of serotonin neurons in the
      dorsal and median raphe. High neurotoxic doses depressed those serotonin neurons
      unresponsive to low doses. Noradrenaline neurons in the locus coeruleus were also
      depressed by moderate doses. Dopamine neurons were unaffected. It is concluded
      that MDMA's unique psychological effects are mediated through a subpopulation of
      serotonergic and noradrenergic neurons, presumably through effects on release
      mechanisms.

PMID- 1979518
TI  - Three histamine receptors (H1, H2 and H3) visualized in the brain of human and
      non-human primates.
AB  - The distribution of histamine H1, H2 and H3 receptors in postmortem human and
      rhesus monkey brain was examined using receptor autoradiography.
      [125I]Iodobolpyramine, [125I]iodoaminopotentine and [3H](R) alpha-methylhistamine
      were used as ligands to label H1, H2 and H3 receptors respectively. The 3
      receptor subtypes were identified in the human and monkey brains. Each receptor
      presented comparable distribution in the two primate brains. H1 and H2 receptors
      were particularly enriched in the caudate and putamen and observed in other brain
      areas such as the neocortex and hippocampus. H3-receptors were found to
      predominate in the basal ganglia where the highest densities were localized in
      the two segments of the globus pallidus. They were also observed in the
      hippocampus and cortical areas. The distribution of these 3 histamine receptors
      in the primate brain suggests the involvement of histaminergic mechanism in the
      functions of many brain areas. In particular, H2 and H3 receptors could play a
      role in the regulation of the basal ganglia functions in primates.

PMID- 1979519
TI  - Lack of excitotoxic cell death in serum-free cultures of rat cerebral cortex.
AB  - The excitotoxicity of glutamate, N-methyl-D-aspartate (NMDA), quisqualate and
      kainate were compared in rat cerebro-cortical cell cultures grown in different
      media. Excitotoxic cell death was examined by phase contrast microscopy and by
      the measurement of lactic dehydrogenase (LDH) activity released in the culture
      medium. Cells grown for 14 days in a serum-free, defined (N2) medium were
      resistant, while sister cultures maintained in the presence of serum responded to
      the excitotoxins by a significant degree of cell death. Cells cultured in serum
      free medium for 7 days, and fed by a serum-containing one for an additional week
      exhibited vulnerability to the excitotoxins. It is concluded that the development
      of excitotoxicity in rat cortical cultures depends on one or more serum
      constituents.

PMID- 1979520
TI  - Somatostatin-28-like immunoreactivity in the rat olfactory bulb.
AB  - Using an immunoperoxidase technique, somatostatin-28-like immunoreactive (LIR)
      neurons were observed in the main and accessory olfactory bulb (MOB and AOB) of
      adult rats. In the MOB, a restricted population of periglomerular cells in the
      glomerular layer, some superficial short-axon cells in the juxtaglomerular layer,
      and some deep short-axon cells in the granule cell layer were IR. The
      periglomerular and the superficial short-axon cells were stained so well that
      they looked like Golgi-impregnated specimens. In the AOB, a very small population
      of small neurons in the glomerular layer, a very few medium-sized and large
      neurons in the external plexiform layer, and some neurons in the granule cell
      layer, which seem to be corresponding to the deep short-axon cells in the MOB,
      were IR. The present results have revealed that different morphological types of
      bulbar neurons are somatostatin-28-LIR; they also indicate neurochemical
      differences between the MOB and AOB.

PMID- 1979521
TI  - Beta-adrenergic agonist-induced long-lasting synaptic modifications in
      hippocampal dentate gyrus require activation of NMDA receptors, but not
      electrical activation of afferents.
AB  - Isoproterenol induced long-lasting potentiation (LLP) of the medial perforant
      path-evoked excitatory post-synaptic potential (EPSP) and long-lasting depression
      (LLD) of the lateral perforant path-evoked EPSP in the absence of perforant path
      activation. The NMDA receptor antagonist D-(-)-2-amino-5-phosphonovaleric acid
      [D(-)APV] blocked the induction of LLP and LLD. After wash, a subsequent exposure
      to isoproterenol induced only LLP of medial perforant path EPSPs; LLD of lateral
      perforant path-evoked EPSPs did not occur. Our results are consistent with the
      hypothesis that beta-adrenergic agonist-induced synaptic modifications in the
      dentate gyrus arise from pre- and postsynaptic events.

PMID- 1979523
TI  - From gradients to axes, from morphogenesis to differentiation.

PMID- 1979522
TI  - A double-blind randomized placebo trial on very high doses of acyclovir in weakly
      symptomatic HIV-patients.
AB  - Herpesvirus infections are thought to be cofactors of the human immunodeficiency
      virus (HIV) disease, and high concentrations of acyclovir (ACV) are active on all
      herpesviruses. Because ACV was shown to delay the cytopathic effect of HIV in
      vitro, we evaluated the effect of intermittent high doses of ACV in mildly
      symptomatic HIV-patients in a randomized double-blind placebo-controlled trial
      with a 4-month treatment period. A total of 30 CDC II and III patients were
      enrolled; 24 (80%) completed the study. Placebo and ACV were given once a week in
      a 3-h infusion with 1 g oral probenecid. Each dose of ACV was 50 mg/kg.
      Pharmacokinetic data were obtained from patients of the preliminary open study.
      The obtained concentrations were effective against both herpesviruses and HIV:
      peak concentrations were 197 and 11 mumol/l in serum and CSF, respectively; the
      CSF:serum ratio of the areas under the curve was 82%. Two patients with placebo
      acquired hairy leukoplakia and detectable antigenemia vs. none in the ACV group
      (p = 0.23). T-helper cell count over the 4-month period decreased in the placebo
      group while it increased in the ACV-treated group (mean of change = -105
      c/microliters vs. +68 c/microliters; p = 0.06). beta 2-microglobulin increased
      with placebo and did not with ACV (mean of change = +0.63 mg/l vs. -0.27 mg/l, p
      less than 0.025). Only one patient had, at one time, transient elevation of
      creatinemia related to ACV. We concluded that weekly high doses of ACV were able
      to delay the progression of some significant markers of HIV disease. Thus,
      preventive/prophylactic treatment of herpesvirus infections could be useful in
      mildly symptomatic HIV patients. Further larger trials using a more feasible
      treatment are warranted.

PMID- 1979524
TI  - What determines the specificity of action of Drosophila homeodomain proteins?

PMID- 1979525
TI  - Mouse Hox-2.2 specifies thoracic segmental identity in Drosophila embryos and
      larvae.
AB  - The mouse genome has a number of homeobox genes that are structurally similar to
      the Drosophila Antenapedia (Antp) gene. We find that one of the mouse Antp-like
      genes, Hox-2.2, when expressed in developing Drosophila cells under control of a
      heat shock promoter, can induce homeotic transformations that are nearly
      identical to those caused by ectopic expression of Antp. In larvae, the Hox-2.2
      induced transformations include thoracic denticle belts in place of head
      structures; in adults, the Hox-2.2 transformations include thoracic legs in place
      of antennae. The phenotypic effects of Hox-2.2 do not depend on the endogenous
      Antp gene, whose spatial limits of expression are unaffected by Hox-2.2
      expression. Thus, in the Drosophila embryo, Hox-2.2 can substitute for some of
      the segmental identity functions of Antp, presumably by regulating the same set
      of downstream genes.

PMID- 1979527
TI  - Does intensive medical therapy influence the outcome in unstable angina?
AB  - Three hundred and forty-six patients of all ages and both sexes were admitted to
      coronary care with documented unstable angina. Management was conservative,
      without the routine use of beta-blockers or calcium antagonists. Mortality was
      3.2%, and the nonfatal myocardial infarction rate was 10.1% during the first 28
      days. After one year, coronary mortality was 10.5% with a nonfatal infarction
      rate of 13.1%. Twenty-six patients were subjected to coronary artery bypass
      surgery, eleven during the first 28 days and fifteen subsequently. No patient
      underwent coronary angioplasty. The factors influencing immediate and long-term
      prognosis in these patients were studied. Persistence of pain in hospital,
      previous chronic angina, and age had an adverse effect on outcome. A total of 143
      patients complained of persistent pain lasting for 24 hours or more. The use of
      beta blockers or calcium antagonists in patients with persistent pain exceeding
      five days did not appear to influence outcome. The current widespread adherence
      to "intensive medical treatment," including the routine use of beta blockers and
      calcium antagonists, is questioned.

PMID- 1979526
TI  - Human Hox-4.2 and Drosophila deformed encode similar regulatory specificities in
      Drosophila embryos and larvae.
AB  - Within the serial array of vertebrate homeobox genes in the Hox complexes, it is
      possible to define a subgroup that is structurally homologous to the Drosophila
      homeotic gene Deformed (Dfd). We wished to test whether a vertebrate Dfd-like
      protein could substitute for any of the regulatory functions of the Dfd protein
      in Drosophila embryos, including its ability to transcriptionally activate the
      Dfd transcription unit. A fusion gene consisting of a heat shock promoter
      attached to the human Hox-4.2 gene was introduced into the Drosophila genome, and
      its regulatory and developmental effects were assayed after heat shock. In
      developing embryonic and larval cells, we find that human Hox-4.2 specifically
      activates ectopic expression of the endogeneous Dfd transcription unit and
      phenocopies a dominant mutant allele of Dfd. Thus, human Hox-4.2 can specifically
      substitute for a normal regulatory function of its Drosophila homolog, Dfd.

PMID- 1979529
TI  - Aggressive behavior in birds: an experimental model for studies of brain-steroid
      interactions.
AB  - 1. Although testosterone (T) stimulates aggressiveness in males of many
      vertebrate species, it is now known that the full expression of T actions in the
      central nervous system requires aromatization to estradiol (E2) and subsequent
      binding of formed E2 to its receptor. 2. We have recently confirmed these as rate
      limiting steps in the control of sex-related and individual differences in
      aggressiveness of the Japanese quail (Coturnix coturnix japonica). 3. In this
      review, we describe some of the neuroendocrine factors which control aggression
      with a focus on our recent studies in quail.

PMID- 1979528
TI  - A case of biopsy-proven myocarditis progressing to autopsy-proven dilated
      cardiomyopathy.
AB  - A 22-year-old man presented with congestive heart failure following flulike
      symptoms. The diagnosis of acute myocarditis was confirmed by endomyocardial
      biopsy, which revealed mild infiltration of inflammatory cells. A favorable
      response to beta-adrenergic receptor blockade was seen, and the patient was
      discharged without symptoms. Five months later, however, congestive heart failure
      recurred, and intracardiac thrombi were demonstrated. The patient died after two
      months. Postmortem examination revealed left ventricular dilatation with slight
      interstitial fibrosis; the diagnosis was dilated cardiomyopathy. Thus,
      progression of biopsy-proven myocarditis to dilated cardiomyopathy 10 months
      after the onset of disease was documented.

PMID- 1979530
TI  - Mechanisms of mammary gland ion transport.

PMID- 1979531
TI  - Activation of dynein adenosine triphosphatase and flagellar motility of
      demembranated spermatozoa by monovalent salts at 40 degrees C in the domestic
      fowl, Gallus domesticus.
AB  - 1. At 40 degrees C, around the normal avian body temperature, demembranated fowl
      spermatozoa with no addition of monovalent chlorides were immotile. 2.
      Demembranated spermatozoa become motile at 40 degrees C when 0.1-0.5 M
      concentrations of NH4Cl, NaCl and KCl were added to the reactivation medium, with
      maximum motility occurring at 0.2-0.3 M in all cases. 3. The addition of NH4Cl,
      NaCl and KCl also stimulated the ATPase activity of crude dynein extract. In
      contrast, LiCl did not appreciably affect motility and ATPase activity. 4. These
      results showed that the flagellar dynein ATPase activity of fowl spermatozoa
      could be stimulated by the addition of certain monovalent chlorides, except LiCl,
      and demembranated spermatozoa might be motile at 40 degrees C.

PMID- 1979532
TI  - Effects of parasympathectomy on protein composition of sympathetically evoked
      parotid saliva in rats.
AB  - 1. Male Wistar rats were given unilateral postganglionic parasympathectomies by
      sectioning the auriculo-temporal nerve. 2. Analyses of the protein compositions
      of sympathetically induced saliva from both glands 1 week later revealed changes
      in the proportions of different secretory proteins, in particular amylase and
      basic proline-rich proteins were decreased. 3. These results suggest that
      parasympathetic impulses are required for the normal synthesis of amylase by
      parotid parenchyma in rats. Basic proline-rich proteins, known to require a
      sympathetic drive for normal synthesis, appear to require a parasympathetic input
      as well.

PMID- 1979533
TI  - Shift of anaerobic to aerobic metabolism in the rats acclimatized to hypoxia.
AB  - 1. Metabolic acclimatization by repeated exposure to a simulated altitude of
      4000, 5000 and 6000 m for 2 hr per day throughout 2 to 11 days was evaluated by
      the increased formation of ketone bodies as a marker of fatty acid oxidation and
      the decreased production of lactate and uric acid, the indicators of anaerobic
      metabolism in rats exposed to an altitude of 8000 m. 2. Pre-exposure of rats to
      an altitude of 5000 m and over caused an acclimatization to hypoxia. The rise of
      the altitude to which rats were pre-exposed reduced the period until the
      acquisition of metabolic acclimatization. 3. Acclimatized rats showed an
      increased activity of mitochondrial glutamate dehydrogenase without changes in
      glycolytic enzyme activity in skeletal muscle, heart and liver. 4.
      Acclimatization to high altitude hypoxia is concluded to involve a shift of the
      anaerobic glycolysis to aerobic metabolism by the increase in the oxidative
      enzymes.

PMID- 1979534
TI  - Extracellular ATP activates Ca2(+)-dependent K+ conductance via Ca2+ influx in
      mouse macrophages.
AB  - 1. Using the perforated patch recording, the effects of ATP on membrane current
      were investigated in mouse peritoneal macrophages. 2. Extracellularly applied ATP
      induced a biphasic current consisting of a initial inward current [Ii(ATP)]
      followed by an outward current [Io(ATP)]. These currents were associated with a
      marked increase in conductance at their peaks. 3. Ii(ATP) reversed close to 0 mV
      and was attenuated by removal of external Na+. 4. Io(ATP) reversed near -80 mV
      and was increased by decreasing the external concentration of K+. 5. Io(ATP) was
      completely abolished by removal of external Ca2+, treatment with an intracellular
      Ca2+ chelator, the acetoxymethyl ester of 1,2-bis (2-aminophenoxy) ethane
      N,N,N',N'-tetra acetic acid (BAPTA-AM) and bath applied quinidine but not
      tetraethylammonium (TEA) or apamin. 6. These results suggest that Ii(ATP) and
      Io(ATP) are due to an activation of nonspecific cationic and Ca2(+)-dependent K+
      conductances, respectively, and raise the possibility that the putative ATP
      receptor may be important in regulating macrophage functions, motility,
      phagocytosis and cytokines secretion.

PMID- 1979536
TI  - Scrotal sonography in infants and children.
AB  - In this review we will attempt to summarize the use of scrotal sonography in
      infants and children. The material is gathered from the literature and from our
      own experience of 197 sonograms performed on 175 pediatric patients. Included
      will be information on testicular development and descent, normal sonographic
      anatomy, classification of scrotal disease, and the final diagnoses of the
      sonograms. Scrotal sonography has proven useful in evaluating undescended testes
      in the inguinal canal and just inside the inguinal ring. It is of limited value
      when the testes are in the abdomen. Sonography can often distinguish the various
      causes of nonpainful scrotal masses such as tumors, hydrocele, and meconium
      peritonitis. Sonography is highly accurate in distinguishing normal from abnormal
      scrotal contents and in separating testicular from extratesticular masses.
      However, sonography does have limitations in distinguishing benign from malignant
      neoplasms or from some inflammatory lesions. Sonography can be successfully used
      in the differential diagnosis of the painful scrotum especially with color flow
      Doppler. Inflammatory diseases that often involve the epididymis can be
      distinguished from torsion. Torsion of the appendages has been diagnosed. In
      cases of scrotal trauma, management decisions are often based on the sonographic
      findings. Conditions that require surgical management such as testicular rupture
      or large testicular hematomas can be recognized. Information is included on a
      variety of miscellaneous conditions such as hydrocele, varicocele, and ambiguous
      genitalia in which sonography has proven valuable.

PMID- 1979535
TI  - The study of energy metabolism in denervated skeletal muscle with 31P-NMR.
AB  - 1. The denervated frog sartorius muscle showed a decrease in the energy store
      more than that in the control. 2. In the caffeine contractures, both the
      denervated and the innervated muscles showed similar sequential changes in the
      relative concentration of phosphocreatine (PCr) to beta-adenosine triphosphate
      (beta-ATP) and inorganic phosphate (Pi) to beta-ATP. Instead, the intracellular
      pH value of the denervated muscle was lower than that of the control. 3. It is
      suggested that phosphate metabolism of the denervated muscle during contracture
      shows little difference from that of the control, nevertheless, the buffering
      capacity is decreased in the early stage of atrophy.

PMID- 1979537
TI  - The different changes of phrenic nerve activity and frequency elicited by
      microinjection of L-glutamic acid into ventrolateral nucleus of the tractus
      solitarius in cats.
AB  - There is only limited information of the neurotransmitters in central respiratory
      control. L-glutamic acid has been proposed as the primary neurotransmitter in the
      nucleus of the tractus solitarius (NTS) in cats. To test whether there is a
      respiratory effect of glutamic acid in the respiratory center or not, we
      microinjected L-glutamic acid (1 M, 0.1 microliter) via 1 microliter Hamilton
      microsyringe into the ventrolateral nucleus of NTS, namely dorsal respiratory
      group (DRG) over two-second intervals with continuous monitoring of phrenic nerve
      activity (PNA), frequency (f), end tidal CO2, blood pressure and heart rate.
      Glutamate induced various respiratory changes including: increase in PNA and f
      decrease in PNA and f [corrected] increase in PNA but decrease in f and decrease
      in PNA but increase in f. In addition to regular changes of PNA or f elicited by
      glutamate microinjection were found. Other patterns of irregular rhythmic changes
      such as absence of PNA, continuous phrenic nerve discharge and irregular phrenic
      nerve discharge with reflex apnea, apneusis and irregular respiration
      respectively were also observed. Glutamic acid appears to significantly modulate
      respiratory drive in DRG. We suggested that L-glutamic acid may be a
      neurotransmitter in the respiratory center and be involved in central respiratory
      control.

PMID- 1979538
TI  - Right ventricular pressure and ventilatory responses to pulmonary gas embolism.
AB  - This study was designed to test the hypothesis that changes in right ventricular
      pressure (PRV) are responsible in part for the altered breathing frequency (f)
      during pulmonary gas embolism (PGE). PGE was induced by infusing air into the
      femoral vein of alpha-chloralose anesthetized dogs. Respiratory flow pattern was
      recorded and analyzed in relation to PRV changes induced resulting from PGE. The
      rise of PRV, whether induced by PGE, by pulmonary artery occlusion, or by acute
      elevation of pulmonary arterial blood flow, was consistently associated with
      increased f. Breathing frequency rose principally through reduction of expiratory
      duration (TE). The inspiratory duration (TI) was shortened somewhat and the
      fractional inspiratory cycle, TI/(TE + TI), increased. The relationships between
      PRV and f were altered by changes of PRV resulting from the administration of
      histamine antagonist, by beta-adrenergic blockade, beta-adrenergic stimulation,
      and by changing pulmonary arterial blood flow. The responses did not occur after
      bilateral cervical vagotomy. These results demonstrate that f during PGE is
      partially regulated in response to changes in PRV and is mediated through the
      vagal afferent.

PMID- 1979539
TI  - Bethanechol induced contraction in mouse spleen.
AB  - Bethanechol was shown to induce contraction in mouse spleen. The possibility of
      initiating such response by stimulating solely muscarinic receptors was tested in
      isolated spleens from mice. The present data showed that bethanechol was able to
      further increase the maximum splenic contraction induced by phenylephrine,
      suggesting that the bethanechol induced contraction was possibly unrelated to
      stimulating adrenergic receptors. Moreover, clonidine which was able to suppress
      the phenylephrine induced splenic contraction, was unable to suppress the splenic
      contraction induced by bethanechol, and this result supported the above notion.
      These data suggest that the bethanechol induced splenic contraction could be the
      result of a direct stimulation of muscarinic receptors in mouse spleens, and an
      indirect effect mediated through the stimulation by bethanechol of sympathetic
      neurotransmitter release from sympathetic varicosities seems unlikely.

PMID- 1979540
TI  - Prevalence and risk factors for tardive dyskinesia: a study in an Italian
      population of chronic schizophrenics.
AB  - The aim of this study was to evaluate tardive dyskinesia (TD) (prevalence and
      possible risk factors, pharmacological and clinical), in a population of
      schizophrenic patients after prolonged institutionalization. A total of 148
      patients (80 male, 68 female) aged between 28 and 87 years (mean 55, SD 11)
      diagnosed according to DSM III were included in the study and assessed for the
      presence and severity of TD using the Abbreviated Rockland Simpson Scale for TD.
      Of the examined population, 32% were found to be affected by TD. Patients over 55
      years had a relative risk of TD that was 2.3 times higher than in subjects under
      55 (P less than 0.05). The most frequent movements were orofacial (60%) and in
      the extremities (56.4%). No significant relationship between duration of
      neuroleptic treatments, illness or hospitalization, anticholinergic drugs and TD
      prevalence was found. Severity was related to age, since there was a positive
      linear relationship between age and Simpson Scale scores (r = 0.45, P less than
      0.01).

PMID- 1979541
TI  - The onset of effect of the H1-antagonist acrivastine ("Semprex") assessed by
      histamine bronchial challenge in volunteers.
AB  - The onset of effect of acrivastine, a new H1-antagonist, has been assessed using
      antagonism of histamine-induced bronchoconstriction in sensitive volunteers.
      Acrivastine administered 30, 45, 60 or 90 min before challenge produced a right
      shift of the histamine dose-response curve of at least 8-fold indicating that a
      clinically desired degree of H1-antagonism was present within 30 min of ingestion
      of the recommended therapeutic dose.

PMID- 1979542
TI  - The association of glycosomal enzymes and microtubules: a physiological
      phenomenon or an experimental artifact?
AB  - Subpellicular microtubules isolated from Trypanosoma brucei parasites were
      fractionated on a phosphocellulose column, and the trypanosomal p52 microtubule
      associated protein was eluted along with two other proteins of 41 and 36 kDa.
      These proteins were found to be the glycosomal enzymes aldolase (41 kDa) and
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH, 36 kDa) by enzyme activity,
      antibody cross-reaction, and N-terminal sequencing. These enzymes were
      coprecipitated with tubulin in the presence of taxol, and aldolase had the
      capacity to polymerize tubulin and crosslink microtubules. Immunolocalization of
      anti-aldolase and anti-GAPDH antibodies did not show an interaction between these
      enzymes and the subpellicular microtubules. The question whether the
      copurification of aldolase and the subpellicular microtubules could reflect a
      physiological phenomenon or may be an experimental artifact is discussed.

PMID- 1979544
TI  - Changes in thermodependence of the tyrosine transaminating activity in
      mitochondria of Drosophila melanogaster larvae due to environmental stress.
AB  - 1. The form of Arrhenius plots of enzyme in mitochondria isolated from Drosophila
      melanogaster larvae exposed to heat shock, ethanol, or ethanol and heat shock,
      solubilized with charged detergents was analysed. 2. Heat shock and ethanol
      caused different changes in membrane microenvironment of the tyrosine
      transaminating activity, which found expression in different forms of Arrhenius
      plots, and different values of activation energy of enzyme. 3. The Arrhenius
      plots of the enzyme from mitochondria of larvae exposed both to ethanol and heat
      shock, solubilized with charged detergents, were similar to those observed for
      mitochondria from organisms exposed only to ethanol.

PMID- 1979543
TI  - Effects of transient forebrain ischemia on peptidergic neurons and astroglial
      cells: evidence for recovery of peptide immunoreactivities in neocortex and
      striatum but not hippocampal formation.
AB  - The effects of transient (30') forebrain ischemia (4 vessel occlusion model) on
      peptidergic neurons and astroglial cells in various diencephalic and
      telencephalic areas have been analyzed. The study was performed at various time
      intervals of reperfusion, i.e. 4 h, 1, 7 and 40 days. Neuropeptide Y (NPY),
      somatostatin (SRIF), cholecystokinin (CCK), vasoactive intestinal polypeptide
      (VIP) and arginine-vasopressin (AVP) immunoreactive (IR) neuronal systems and
      glial fibrillary acidic protein (GFAP)-IR glial cells have been visualized by
      means of the indirect immunoperoxidase procedure using the avidin-biotin
      technique. The analysis was performed by means of computer assisted
      microdensitometry and manual cell counting. At the hippocampal level a huge
      reduction of neuropeptide (CCK, SRIF, VIP) IR cell bodies was observed, still
      present 40 days after reperfusion. On the contrary, in the frontoparietal cortex
      the number of the neuropeptide (CCK, SRIF, VIP, NPY) IR neurons showed a decrease
      at 4 h, 1 and 7 days after reperfusion followed by a complete recovery at 40
      days. A rapid reduction followed by an almost complete recovery (7 days after
      reperfusion) was also observed at striatal level where SRIF- and NPY-IR neurons
      were detected. A marked decrease of NPY-IR terminals was observed in the
      paraventricular and periventricular hypothalamic nuclei and in the
      paraventricular thalamic nucleus. AVP-IR was markedly reduced in the
      magnocellular part of the paraventricular nucleus throughout the analyzed period
      (7 days after reperfusion). GFAP-IR was increased in the hippocampal formation
      and neostriatum while a not consistent increase was observed at neocortical
      level. These data point to a differential recovery of peptide-IR and to a
      different astroglial response in the various brain areas after transient
      forebrain ischemia. Region-specific factors rather than factors related to
      neuronal chemical coding seems to play a major role in determining the
      vulnerability of neuronal populations to transient ischemia.

PMID- 1979546
TI  - [Interindividual hyperpolymorphism of autosomal satellites III of human DNA].
AB  - Hypervariability of DNA restriction fragments from pericentromeric
      heterochromatin detected by autosomal "classic" DNA of satellite III has been
      demonstrated in this work. Using hybridization probe of satellite III DNA
      localized predominantly on the chromosome 9 strong interindividual differences in
      the sets of polymorphic DNA restriction fragments inherited from both paternal
      and maternal sides as well as intraspecies amplifications of some variants of the
      satellite III were observed. The number and intensity of restriction bands are
      identical in both sexes. It is suggested that strong interindividual DNA
      variability may be largely specified by high level of DNA spot mutability in
      satellites III. Pericentromeric "classic" satellites III may serve as efficient
      markers for identification of individuals and for molecular-genetic mapping of
      human genome pericentromeric regions.

PMID- 1979545
TI  - Persistent ectopic expression of Drosophila homeotic genes resulting from
      maternal deficiency of the extra sex combs gene product.
AB  - Like other members of the Polycomb group, the extra sex combs gene (esc) is
      required for the correct repression of loci in the major homeotic gene complexes.
      We show here that embryos lacking both maternal and zygotic esc+ function display
      transient, general derepression of both the Ultrabithorax (Ubx) and Antennapedia
      (Antp) genes during germ band shortening, but Sex combs reduced (Scr) expression
      is almost normal in the epidermis and lacking in the central nervous system
      (CNS). In addition, embryos that are maternally esc- but receive two paternal
      copies of esc+ often are characterized by ectopic expression of the three
      homeotic genes, especially Ubx and Antp in the CNS. Imaginal discs from these
      paternally rescued embryos may show discrete patches of expression of Ubx and Scr
      in inappropriate locations. Thus, lack of esc+ function during a brief period in
      early embryogenesis results in a heritable change in determined state, even in a
      genetically wild type animal. Within these ectopic patches, homeotic gene
      expression may be regulated by the disc positional fields and by cross-regulatory
      interactions between homeotic genes.

PMID- 1979547
TI  - Unique composition of plastid chaperonin-60: alpha and beta polypeptide-encoding
      genes are highly divergent.
AB  - Molecular chaperones of the chaperonin family occur in prokaryotes and in
      plastids and mitochondria. Prokaryotic and mitochondrial chaperonin-60 oligomers
      (Cpn-60) are composed of a single subunit type (p60cpn-60). In contrast,
      preparations of purified plastid Cpn-60 contain approximately equal quantities of
      two polypeptides, p60cpn-60 alpha and p60cpn-60 beta, with slightly different
      electrophoretic mobilities. We have isolated cDNA clones encoding plastid p60cpn
      60 alpha and p60cpn-60 beta polypeptides from Brassica napus and Arabidopsis
      thaliana. The unexpected degree of sequence divergence observed between p60cpn-60
      alpha and p60cpn-60 beta raises questions concerning the structure of the
      oligomer and the functions of these polypeptides. We have also found an amino
      acid sequence motif within all p60cpn-60 sequences which resembles the p10cpn-10
      sequences.

PMID- 1979548
TI  - Stem-loop structures at the 3' end of tobacco Rubisco large subunit mRNA.
AB  - There are two inverted repeat nucleotide (nt) sequences, each capable of forming
      a stem-loop structure (sls) at the 3' end of the tobacco Rubisco large subunit
      mRNA (rbcL). The smaller sls is followed by a larger sls. The in vivo functions
      of the 3' sls of the rbcL mRNA were characterized using the Escherichia coli
      system. S 1 mapping of the rbcL transcripts synthesized in E. coli revealed that
      the 3' end of a major transcript in the bacterial cell is almost identical to the
      3' end of authentic chloroplast (cp) rbcL mRNA. This native 3' end is located 4
      nt downstream from the larger sls for the cp mRNA and 6 nt for the bacterial
      transcript, respectively. Deletion experiments show that the larger sls is
      essential for producing the native 3' end of rbcL mRNA in E. coli. The sls do not
      function as an efficient transcription terminator but can stabilize upstream mRNA
      segments in vivo.

PMID- 1979549
TI  - Location of the dihydroorotase domain within trifunctional hamster dihydroorotate
      synthetase.
AB  - Mammalian dihydroorotase (DHOase, EC 3.5.2.3) is part of a trifunctional protein,
      dihydroorotate synthetase which catalyzes the first three reactions of de novo
      pyrimidine biosynthesis. We have subcloned a portion of the cDNA from the plasmid
      pCAD142 and obtained a nucleotide sequence which extends 2.1 kb in the 5'
      direction from the sequence encoding the aspartate transcarbamoylase (ATCase)
      domain at the 3'-end of the cDNA. The DHOase and ATCase domains have been
      purified from an elastase digest of the trifunctional protein and subjected to
      amino acid (aa) sequencing from their N termini. The sequence of the N-terminal
      24 aa of the DHOase domain has been obtained and aligned with the cDNA sequence.
      The C-terminal residues of the DHOase domain have been identified as Leu followed
      by Val which, when taken with partial sequences of the CNBr fragments of this
      domain, defines the coding sequence of the active, globular DHOase domain
      released by proteolysis. Prediction of protein secondary structure from the
      deduced aa sequence showed that the DHOase domain (Mr 37,751) is separated from
      the C-terminal ATCase domain (Mr 34,323) by a bridging sequence (Mr 12,532)
      consisting of multiple beta-turns.

PMID- 1979550
TI  - [First aid against animal poisons. 4: Jellyfish].

PMID- 1979551
TI  - A quantitative analysis of T lymphocyte populations in human liver allografts
      undergoing rejection: the use of monoclonal antibodies and double immunolabeling.
AB  - The aim of this study was to quantitate T-cell populations infiltrating portal
      tracts, bile ducts and hepatic lobules in 82 biopsy specimens from 25 patients
      after orthotopic liver transplantation. Biopsy specimens taken immediately after
      revascularization of the graft were used as controls. Patients studied include 18
      with initial rejection episodes, 11 with unresolved rejection, five with
      vanishing bile duct syndrome and eight patients with other forms of liver injury.
      Quantitation was done in a blinded fashion for the first 20 biopsy specimens. A
      double immunolabeling technique was used to simultaneously immunolabel bile duct
      structures (with anti-major histocompatibility complex class II or antikeratins)
      and lymphoid populations (with anti-CD2, anti-CD4 or anti-CD8). This facilitated
      the accurate quantitation of intraepithelial lymphocytes within bile ducts. This
      technique also enabled simultaneous detection of CD4 and CD8 antigens on
      lymphocytes in portal tracts. The predominant lymphocyte subtype within biliary
      epithelium during acute and chronic rejection was of the CD2+/CD8+ phenotype.
      CD8+/CD4+ ratio in bile ducts was approximately 5:1 in acute, unresolved and
      chronic rejection. In vanishing bile duct syndrome, double immunolabeling enabled
      the detection of destroyed interlobular bile duct remnants that were not apparent
      on routine hematoxylin and eosin staining. Attached to some of these structures
      were CD8+ lymphocytes. Lobular CD8+ cells were not prominent in acute rejection
      but increased significantly in biopsy specimens from patients with unresolved and
      chronic rejection. In chronic rejection, a selective increase was seen in these
      CD8+ cells in centrizonal regions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1979552
TI  - The role of the epidermal growth factor receptor and the c-erbB-2 protein in
      breast cancer.
AB  - Breast cancer cells are derived from epithelial cells lining the ducts of the
      breast. One of the fundamental characteristics that distinguish tumour cells from
      normal cells is that cancer cells grow in an apparently unregulated way.
      Understanding the mechanisms that regulate the growth and differentiation of
      normal breast epithelial cells and the differences between these systems in
      cancer cells is one of the central goals of research into the cell biology of
      breast cancer.

PMID- 1979553
TI  - New strategy for discovery of enzyme inhibitors: screening with intact mammalian
      cells or intact microorganisms having special functions.

PMID- 1979554
TI  - Pefloxacin in clinical practice. Report of a symposium held in Lisbon, 22-23
      March 1990. Proceedings.

PMID- 1979556
TI  - Clonazepam and bipolar affective disorder.

PMID- 1979555
TI  - Injection site reactions after intramuscular administration of haloperidol
      decanoate 100 mg/mL.
AB  - The authors report four cases of injection site reaction after intramuscular
      administration of haloperidol decanoate 100 mg/mL. In each case, the injection
      site became edematous, red, pruritic, and tender, and a palpable mass remained
      for up to 3 months. No systemic symptoms were reported. All four patients had
      previously received the 50 mg/mL haloperidol decanoate injection without
      incident. Two of these events followed the initial injection of haloperidol
      decanoate 100 mg/mL. Rechallenge with the 100 mg/mL product in one case and the
      50 mg/mL product in two resulted in similar reactions. The incidence of this
      reaction at the authors' facility is estimated to be 7.7%. The authors speculate
      that the reaction is most likely to be related to the concentration of
      haloperidol decanoate in the injection.

PMID- 1979557
TI  - Serotonin reuptake inhibition in the management of depression. Proceedings of a
      satellite symposium in connection with the VIII World Congress of Psychiatry.
      October 18, 1989, Athens, Greece.

PMID- 1979558
TI  - Taxol influences control of protofilament number at microtubule-nucleating sites
      in Drosophila.
AB  - Control of protofilament number has been investigated using Drosophila wings at a
      stage when 15-protofilament microtubules assemble under normal conditions.
      Microtubule nucleation still progressed at the usual microtubule-nucleating sites
      in the presence of taxol. However, provided taxol was introduced before
      microtubule nucleation began, few microtubules with 15 protofilaments assembled.
      Most microtubules were composed of 12 protofilaments (a previously undetected
      value for Drosophila) or 13 protofilaments (which is the value for microtubules
      in most eukaryotic cells). Unexpectedly, a comparatively mild challenge to
      control of nucleation (in vitro wing culture) also promoted assembly of 13
      protofilament microtubules. Hence, the microtubule-nucleating sites may possess a
      relatively labile control specifying 15 protofilaments superimposed upon that for
      maintaining 13-protofilament fidelity.

PMID- 1979560
TI  - Stepwise gradient in thin-layer chromatography of Chelidonium alkaloids.

PMID- 1979559
TI  - Blood platelet formation in vitro. The role of the cytoskeleton in megakaryocyte
      fragmentation.
AB  - We have developed a unique in vitro model that promotes differentiation of
      megakaryocytes into platelets. When megakaryocytes isolated from guinea pig bone
      marrow were cultured on hydrated rat tail collagen gels, cells spontaneously
      formed elongated, beaded processes that fragmented to yield cytoplasmic pieces
      with the same size and internal composition as individual platelets. Addition of
      nocodazole at the initiation of cultures blocked process formation, while
      addition of nocodazole to cells with previously established processes resulted in
      their retraction. The addition of taxol to cultures resulted in abnormally thick
      processes that were tightly adherent to the underlying substratum, and did not
      bead or fragment. Cytochalasin D accelerated process formation and fragmentation
      of megakaryocytes cultured on collagen gels by twofold. On the basis of these
      results, we propose a model for platelet formation in culture that involves the
      following steps: adherence of megakaryocytes to the underlying extracellular
      matrix; dilation of the demarcation membrane system and breakdown of the actin
      rich peripheral zone; microtubule-based extension of pseudopodia, which are no
      longer adherent to the substratum; and fragmentation into platelets by the
      coalescence and fusion of demarcation membrane vesicles with the plasma membrane.
      We feel that this distinctive culture system closely approximates
      thrombocytopoiesis in vivo, thus allowing detailed elucidation of this important
      process.

PMID- 1979561
TI  - Chromatography of beta-adrenergic blocking agents.
AB  - The determination of beta-blockers has posed pharmaceutical analysts with a
      variety of problems arising from the essential characteristics of these compounds
      as bases and the variability of physicochemical properties of individual drugs.
      Liquid chromatography has become the favoured method of analysis and to a certain
      extent there is a standardised approach to analysis based on either solvent or
      solid-phase extraction and reversed-phase high-performance liquid chromatography
      coupled to fluorescence detection. The analyst must be aware of interactions
      occurring during extraction stages. All manipulations should be fully evaluated
      for individual drugs and metabolites prior to use. Other analytical options are
      chosen for specific or more demanding applications. The use of unmodified silicas
      for the liquid chromatography of beta-blockers (and other basic drugs) is an
      example of a potential alternative mode of chromatography. The stereoselectivity
      of the pharmacology of beta-blockers has spawned a great deal of literature
      describing the resolution of enantiomers by chromatographic methods. It is
      envisaged that this area will achieve greater prominence in the future as drug
      development pursues optical purity. The demand for the availability of
      enantiomerically pure pharmaceutical preparations will certainly see developments
      for preparative-scale separations as well as analytical methods and will surely
      promote developments in new and established methods of chromatography.

PMID- 1979562
TI  - Chromatography of histamine H1- and H2-receptor blockers in biosamples.
AB  - This paper reviews thin-layer chromatographic, high-performance liquid
      chromatographic, gas chromatographic and gas chromatographic-mass spectrometric
      procedures for the identification and quantification of sixty histamine H1- and
      ten H2-receptor blockers in biosamples, published from 1984 to 1989. The
      biomedical importance of the published procedures and consequences for their
      choice, the sample preparation and the chromatography itself are discussed. The
      fundamental information about the biosample assayed, work-up, stationary and
      mobile phase, detection mode and sensitivity of each procedure is summarized in
      seven tables. They are arranged according to the chromatographic method and the
      category of histamine receptor blockers. Examples of typical chromatographic
      separations are presented in three figures.

PMID- 1979563
TI  - Bioanalysis of anti-ulcer agents.
AB  - In reviewing the analytical methods for the analysis of anti-ulcer drugs we
      observed an increase in the utilization of solid-phase extraction techniques,
      though the traditional liquid-liquid methods are still predominant. Liquid
      chromatographic techniques are employed more than gas chromatographic methods
      which reflects the general trend in chromatographic analysis for analytes in the
      nanogram range. We foresee a continued increase in the use of solid-phase
      extraction methodology (automated or otherwise) due to the potential for dramatic
      decreases in extraction times, cost and significant enhancement of extraction
      efficiency. Because the therapeutic concentrations of these drugs tend to be in
      the low nanogram range in plasma and the current trend in drug development is
      toward more potent agents, we anticipate the application of more sensitive liquid
      chromatographic detection techniques such as electrochemical and
      chemiluminescence detection to overcome the limitations of currently used
      technology.

PMID- 1979564
TI  - Chromatography of benzodiazepines.
AB  - An overview of methods for the determination of benzodiazepines in biological
      media, based on the application of chromatographic techniques, is presented. A
      general discussion of the techniques in terms of stability, selectivity,
      validation, standardization, detection and sensitivity is given. No single
      technique can be claimed as the method of choice for benzodiazepines. Gas
      chromatography with electron-capture detection has some strong claims and shows
      generally good sensitivity and reproducibility. High-performance liquid
      chromatographic equipment is readily available in most laboratories. The ultimate
      choice of an assay method for benzodiazepines will be determined by the clinical
      application (routine monitoring, pharmacokinetics, overdose, forensic medicine)
      and by the characteristics of the benzodiazepine, the expertise of the analyst,
      the equipment available, the desired sensitivity and specificity and the time
      involved in method development or adaptation and validation.

PMID- 1979565
TI  - Stimulants for ADHD in child patients with Tourette's syndrome: the issue of
      relative risk.

PMID- 1979566
TI  - Effects of clozapine on treatment-resistant akathisia and concomitant tardive
      dyskinesia.

PMID- 1979567
TI  - The pharmacologic treatment of neuroleptic-induced akathisia.

PMID- 1979569
TI  - International Sardinian Congress on Pediatric Endocrinology. Porto Cervo,
      Sardinia, October 7-10, 1990. Abstracts.

PMID- 1979568
TI  - Tardive Meige syndrome responsive to clozapine.

PMID- 1979570
TI  - Workshop on Endocrine Problems in Thalassemia. Porto Cervo, Sardinia, October 11,
      1990. Abstracts.

PMID- 1979571
TI  - Control of viral infections in hospitals.

PMID- 1979572
TI  - Factors affecting the incidence of postoperative wound infection.
AB  - A prospective study of postoperative wounds was carried out in West Dorset to
      determine the incidence of infection, describe the time distribution of
      presentation before and after discharge from hospital and identify possible
      contributory factors. There were 702 consecutive patients admitted to the study
      (600 in-patients and 102 day cases). Fifty one became infected (47 in-patients
      and 4 day cases), corresponding to an overall infection rate of 7.3%. Over 50% of
      infections presented during the first week after operation, and almost 90% were
      diagnosed within 2 weeks of surgery Twenty-eight (55%) wounds that became
      infected presented after hospital discharge. Of 23 specific aetiological
      variables studied, four (age, preoperative stay, shaving and the surgeon) were
      shown to have a statistically significant association with the development of
      wound infection. A strong association between the individual surgeon and the
      development of a wound infection was demonstrated and this supports the need for
      routine surgical audit.

PMID- 1979573
TI  - The impact of methicillin- and aminoglycoside-resistant Staphylococcus aureus on
      the pattern of hospital-acquired infection in an acute hospital.
AB  - Infections due to methicillin- and aminoglycoside-resistant Staphylococcus aureus
      (MARSA) appeared in a new teaching hospital shortly after it opened. The effect
      this had on the pattern of hospital-acquired infections in the four years that
      followed is described. No control measures were applied and MARSA became endemic.
      New infections appeared at a rate of about four for each 1000 patients
      discharged. It established itself at different levels of incidence in various
      specialist units, patients under intensive care being most severely affected.
      MARSA was implicated in half of all hospital-acquired infections due to S. aureus
      but it was not more pathogenic than its more sensitive counterpart. It had little
      impact on the life of the hospital.

PMID- 1979574
TI  - Perioperative wound infection in elective orthopaedic surgery.
AB  - Between 1981 and 1987, 12,907 [corrected] consecutive open elective orthopaedic
      procedures were performed. The in-patient infection rate was 1.43%. There was a
      significantly greater risk of infection in revision total knee replacement
      (15.3%), ankle fusion (9.3%), subtalar fusion (5.8%), primary total knee
      replacement (5.7%), spinal fusion (5.7%) and revision total hip replacement
      (4.5%). Revision surgery carried approximately a threefold greater risk than
      primary procedures. Staphylococci were present in 83% of positive wound cultures.
      Infection rates varied among surgeons but when number and type of procedure were
      taken into account only two surgeons differed significantly from that expected.
      Patients undergoing spinal and hindfoot fusion suffered considerable morbidity as
      a consequence of wound infection. Antibiotic prophylaxis may be helpful in these
      procedures.

PMID- 1979575
TI  - A bacteriological assessment of ampicillin with sulbactam as antibiotic
      prophylaxis in patients undergoing biliary tract operations. The West of Scotland
      Surgical Infection Study Group.
AB  - A prospective audit of 644 patients undergoing biliary tract operations has been
      conducted in ten district general hospitals. All patients received a single dose
      of ampicillin 2 g and sulbactam 1 g as antibiotic prophylaxis. Bacteria were
      cultured from the bile of 121 patients. In patients with sterile bile the
      incidence of postoperative infection was 2.5%, while in those with colonized bile
      it was 22% (P less than 0.0001). The 35 patients from whose bile bacteria of two
      or more species were isolated, had a higher incidence of wound infection (34%)
      than those whose bile yielded only one species of bacterium (17%; P less than
      0.05). Seventeen of the 27 patients with colonized bile who developed
      postoperative infection were shown to be infected by the same organisms that had
      been isolated from their bile. The patients whose bile yielded organisms
      resistant to the prophylactic antibiotic combination did not have a significantly
      higher rate of infection than those from whose bile only sensitive organisms were
      obtained. A marked difference in sensitivity patterns between the participating
      hospitals was observed.

PMID- 1979576
TI  - Mycobacterium chelonei isolation from broncho-alveolar lavage fluid and its
      practical implications.
AB  - Mycobacterium chelonei was isolated from the broncho-alveolar lavage fluid of
      seven patients on eight occasions over a 6-month period. The same bacterium was
      identified in the hospital water supply. Despite the use of a recommended
      disinfection procedure, it proved impossible to eradicate the organism until the
      bronchoscopes were treated with ethylene oxide and the use of tap water in
      rinsing was abandoned.

PMID- 1979577
TI  - A comparison of four culture methods for diagnosing infection in continuous
      ambulatory peritoneal dialysis.
AB  - Dialysate effluent from 41 patients presenting with 54 episodes of CAPD
      peritonitis was examined by four culture techniques, three employing methods for
      the lysis of peritoneal leucocytes. The most efficient method employed a
      distilled water lysis-centrifugation technique (81% of episodes culture
      positive). Filtration (without leucocyte lysis) was less effective (74% culture
      positive). The results of a mechanical leucocyte lysis technique were less
      satisfactory still, the culture positive rate of 74% being compromised by the
      recovery of the infecting organism in low numbers, and by an association with a
      high incidence of plate contamination. The results of a bile-salt lysis technique
      were the least satisfactory (67% culture-positive).

PMID- 1979578
TI  - Elution of disinfectant from polyurethane cannula tubing.
AB  - Cannula tubing (1.6 mm external, 1 mm internal diameter) was fabricated from
      medical grade polyurethane containing 2% 2,4,4'-trichloro-2'-hydroxydiphenyl
      ether ('Irgasan', Ciba-Geigy). When shaken with 10 ml of phosphate-buffered
      saline an equilibrium was set up with only traces of 'Irgasan' in the aqueous
      phase. When phosphate-buffered saline flowed through the tubing, 0.26 mg of
      'Irgasan' per g of tubing per day was eluted, and this was not detectably
      increased by buffers of pH 3 or pH 8.5. However, a 20% lipid emulsion eluted 6 mg
      per g of tubing per day with a flow rate of 250 ml per day and 11 mg with a flow
      rate of 11 per day. These results scaled up show that a 7.11 g Hickman catheter
      would lose 78 mg of Irgasan in the first day with Intralipid, compared to 1.8 mg
      with PBS. If elution by tissue fluids (including blood) does not exceed that by
      Intralipid then comparison with available toxicological data suggests an adequate
      margin of safety for adults, but not for premature babies.

PMID- 1979579
TI  - Use of in-line filters for intravenous infusions.

PMID- 1979580
TI  - Lactate dehydrogenase isoenzyme electrophoresis as a typing method for
      Enterobacter cloacae, Klebsiella oxytoca and Proteus mirabilis.

PMID- 1979582
TI  - Isolated peripheral T cells from GvHR recipients exhibit defective IL-2R
      expression, IL-2 production, and proliferation in response to activation stimuli.
AB  - Graft-vs-host reactions (GvHR) following the injection of class I/II MHC
      disparate parental cells into unirradiated F1 recipient mice result in the
      development of marked immune dysfunction. Following negative selection using
      adherence and antibody and complement depletion, highly purified T cells were
      examined to determine their ability to undergo activation. Three weeks after GvHR
      initiation, unstimulated splenic T cells from GvHR mice displayed normal CD3 and
      IL-2R expression but elevated expression of class I MHC and Ly-6A/E antigens.
      Despite culture with normal F1 accessory cells, both CD4+ and CD8+ GvHR T cells
      exhibited low levels of proliferation to both Con A and anti-CD3 mAb. Although
      following exposure for 12 h to either of these stimuli, GvHR T cells expressed
      normal levels of IL-2R, expression was greatly decreased vs normal T cells
      between 24 and 48 h. In addition, at no timepoint was detectable IL-2 produced by
      GvHR T cells. Importantly, mixing experiments did not demonstrate detectable
      suppressive activity in the purified GvHR T cell subsets. GvHR T cells were also
      tested for their ability to respond to stimuli in the absence of any accessory
      cell population. These cells again did not proliferate to levels equivalent to
      normal T cells. Incubation with PMA and either cytokines (Con A supernatant, rIL
      7) or anti-CD3 mAb resulted in only low levels of proliferation in GvHR T cells.
      Notably, at high ionomycin concentrations together with PMA, GvHR T cells did
      proliferate to equivalent levels as normal cells. However, with decreasing
      concentrations of ionophore, these cells failed to proliferate as well as normal
      cells. In total, these findings demonstrate that GvHR T cells are phenotypically
      and functionally distinct from normal T cells. The results suggest that GvHR T
      cells themselves may contribute to the well-characterized immune depression
      occurring in recipients undergoing GvHR.

PMID- 1979581
TI  - Cell surface modulation of CD26 by anti-1F7 monoclonal antibody. Analysis of
      surface expression and human T cell activation.
AB  - In this paper, we examined in detail the ability of anti-1F7 to modulate 1F7
      (CD26) surface expression as well as analyzed the functional relationship between
      the surface expression of CD3, CD2, and CD26 and human T cell activation. We
      showed that anti-1F7-induced modulation is an energy-dependent process that
      occurs via capping and internalization of the Ag-antibody complex. Although the
      recovery rate for Ag reexpression of 1F7 following optimal modulation is
      relatively delayed, reexpression of 1F7 is greatly accelerated following phorbol
      ester treatment. Most importantly, we demonstrated that modulation of the CD26 Ag
      leads to an enhancement in the proliferative activity of modulated human T cells
      treated with anti-CD3 or anti-CD2, which is preceded by an enhancement in Ca2+
      mobilization. CD26 modulation also led to an increase in anti-CD3- or anti-CD2
      mediated T cell clone proliferation. Finally, whereas modulation of the CD26 Ag
      has an effect on CD3- or CD2-induced T cell activation, modulation of the CD3/TCR
      complex inhibits the proliferative response of T cells incubated with anti-CD3
      plus anti-1F7 or anti-CD2 plus anti-1F7. However, modulation of the CD2 structure
      does not affect anti-CD3- plus anti-1F7-induced human T cell activation. The
      above results thus provide additional evidence that the CD26 Ag plays an integral
      role in the regulation of human T cell activation.

PMID- 1979583
TI  - Thymic stromal cell clone with nursing activity supports the growth and
      differentiation of murine CD4+8+ thymocytes in vitro.
AB  - Thymic stromal cell clone, TNC-R3.1 cell, was established from spontaneous AKR/J
      mouse thymoma. TNC-R3.1 cell, which has the similar properties to thymic nurse
      cells, formed a unique complex with normal thymocyte subpopulations. Flow
      cytometry analysis demonstrated that CD4+8+ and CD4-8- immature thymocytes
      preferentially interacted with TNC-R3.1 stromal cell clone. CD4+8+ thymocytes,
      which interacted with TNC-R3.1 stromal cell clone, contained a higher proportion
      of large size and cycling T cells than did noninteracting CD4+8+ thymocytes. As
      is generally accepted, CD4+8+ thymocytes did not respond to any stimulation such
      as IL-2, anti-CD3 mAb (2C11), or IL-2 plus 2C11. However, culture of isolated
      CD4+8+ thymocytes on TNC-R3.1 stromal cell monolayer in the presence of
      suboptimal dose of IL-2 induced a significant cell growth. Moreover, the addition
      of 2C11 and IL-2 into this coculture system resulted in a dramatic increase of
      the proliferative response of thymocytes. Flow cytometry analysis showed the
      proliferating cells on TNC-R3.1, which originated from CD4+8+ thymocytes, were
      mostly TCR-alpha beta+ CD3+CD4-8+ T cells. These results provide in vitro
      evidence that CD4+8+ thymocytes are at an intermediate stage of T cell maturation
      and TNC-R3.1 stromal cell clone induces the growth and differentiation of CD4+8+
      thymocytes into CD4-8+ T cells.

PMID- 1979584
TI  - Selective signal transduction through the CD3 or CD2 complex is required for
      class II MHC expression by human T cells.
AB  - Ag-dependent activation of human T cells results in high level expression of
      class II MHC molecules. As part of this process, Ag recognition by TCR generates
      a series of second signals including protein kinase C, tyrosine kinase, and Ca2+
      mobilization. To investigate the role of these second messengers in class II MHC
      expression, purified T cells were first stimulated by PMA, ionomycin, OKT3
      accompanied by IL-2, or the mitogenic anti-CD2 antibodies T112 and T113 and were
      then stained with FITC-conjugated anti-class I and -class II MHC antibodies for
      analysis by flow cytometry. OKT3 and IL-2 induced optimal expression of HLA-DR
      (DR) on 70% of T cells with high density. Despite their high mitogenicity,
      induction of class II MHC expression by PMA, even with co-stimulation by
      ionomycin, was reduced to less than 20% of T cells, with an intensity 50-fold
      lower than in OKT3/IL-2-stimulated T cells. Furthermore, PMA inhibited class II
      MHC expression by OKT3/IL-2-stimulated T cells in a dose-dependent manner and
      additional stimuli, such as IL-1, IL-4, IFN-gamma, TCR cross-linkers, or
      monocytes, did not restore class II MHC expression by PMA-activated T cells. DR
      beta mRNA analysis showed that the low induction of class II molecules by PMA
      extends to the transcriptional level. Interestingly, anti-T112 and anti-T113
      induced not only proliferation of T cells but also DR expression on more than 90%
      of T cells. These results indicate that transduction of a specific signal,
      probably selective phosphorylation of the CD3 molecule, contributes to class II
      MHC induction in the process of T cell activation.

PMID- 1979585
TI  - Programmed T lymphocyte death. Cell activation- and steroid-induced pathways are
      mutually antagonistic.
AB  - Both cellular activation signals and exposure to glucocorticoids such as
      dexamethasone (Dex) cause programmed cell death in T cell hybridomas. When cells
      were activated in the presence of Dex, however, the degree of killing that was
      achieved by either stimulus alone was markedly reduced. Dex-induced programmed
      cell death of normal T cell clones was also prevented by cellular activation.
      Cyclosporin A (CsA) completely blocked the activation-induced death of T cell
      hybridomas, but actually enhanced the killing caused by Dex. The addition of CsA
      to activated T cell hybridomas in the presence of Dex allowed killing to proceed,
      consistent with ability of CsA to block activation-induced nuclear gene
      transcription. A number of independent approaches were used to explore the effect
      of activation on the glucocorticoid signaling/effector pathway. First, RU-486,
      which binds the glucocorticoid receptor and is a potent competitive antagonist of
      Dex, did not inhibit activation-induced cell killing. Second, activation of T
      cell hybridomas did not cause the translocation of the glucocorticoid receptor
      from the cytoplasm to the nucleus, nor did it prevent the receptor translocation
      induced by treatment with Dex. Finally, T cell hybridomas were transfected with a
      plasmid containing the chloramphenicol acetyltransferase (CAT) gene under the
      control of two tandemly arranged glucocorticoid-responsive elements. Activation
      of these cells did not induce CAT activity, and did not inhibit the CAT activity
      induced by Dex. In fact, there was a paradoxical increase in CAT activity when
      cells were treated with both stimuli. We conclude that cellular activation does
      not directly utilize the glucocorticoid receptor nor the glucocorticoid pathway
      when inducing programmed cell death. Furthermore, the ability of activation to
      inhibit Dex-mediated killing is not due to interference with the classical
      glucocorticoid signaling pathway, up to and including the initiation of gene
      transcription. Alternative mechanisms of antagonism, as well as the possible
      relevance of this phenomenon to the positive selection of self-recognizing
      thymocytes, are discussed.

PMID- 1979586
TI  - A murine very late activation antigen-like extracellular matrix receptor involved
      in CD2- and lymphocyte function-associated antigen-1-independent killer-target
      cell interaction.
AB  - CD2 and lymphocyte function-associated antigen (LFA)-1 are well known as T cell
      adhesion molecules involved in killer-target cell interactions. However, our
      recent study revealed that molecule(s) other than CD2 and LFA-1 might be involved
      in the lymphokine-activated killer (LAK) cell cytotoxicity against certain target
      cells. In order to characterize such unknown molecules, we established a mAb (RMV
      7) which could inhibit CD2/LFA-1-independent LAK cell cytotoxicity and binding to
      target cells at the effector site. The Ag identified by RMV-7 appeared on splenic
      T cells late after mitogenic stimulation and was a noncovalently linked
      heterodimer composed of a 140-kDa alpha-chain and a 95-kDa beta-chain. RMV-7
      blocked LAK cell binding to fibronectin (FN), fibrinogen, and vitronectin but not
      that to laminin or type IV collagen, indicating that the RMV-7-defined molecule
      is a unique extracellular matrix receptor for FN, fibrinogen, and vitronectin.
      One of its ligand, FN, was found on the surface of several target cells, and LAK
      cell cytotoxicity against them was blocked by anti-FN antibody at the target
      site. Similarly, cytotoxicity of a H-2d-specific CTL clone was inhibited by RMV-7
      and anti-FN antibody as well. These results indicate that a unique very late
      activation Ag-like extracellular matrix receptor on murine CTL and LAK cells
      contributes to target cell binding and cytotoxicity.

PMID- 1979588
TI  - [Biochemical mechanisms of antitumor drug resistance].

PMID- 1979589
TI  - [Angiographic anatomy and pathogenetic mechanisms of angina pectoris:
      implications regarding medical therapy].

PMID- 1979587
TI  - Effects of recombinant tumor necrosis factor-alpha on cultured microvascular
      endothelial cells derived from human dermis.
AB  - We investigated the effects of recombinant human tumor necrosis factor-alpha
      (TNF) on cell proliferation and on expression of MHC class II antigens and
      intercellular adhesion molecule ICAM-1 in human dermal microvascular endothelial
      cells (HDMEC) derived from human foreskin. Second-passage HDMEC were treated with
      0.1-10,000 U/ml TNF for up to 6 d, and cell growth was assessed by cell counts
      and a recently developed fluorogenic assay using 4-methylumbelliferyl heptanoate
      as a substrate. APAAP immunocytochemistry was performed using monoclonal
      antibodies against HLA-DR, HLA-DQ, and ICAM-1. TNF did not markedly inhibit the
      growth of HDMEC but induced expression of HLA-DR (1,000 U/ml and more) and of
      ICAM-1 (1 U/ml and more). Combination with interferon-gamma led to synergistic
      ICAM-1 induction. These results demonstrate a profound effect of TNF on the
      activation of dermal microvascular endothelial cells and suggest a major role of
      TNF in the mediation of leucocyte adhesion to endothelial cells of the skin
      microvasculature with possible implications for the initiation and maintenance of
      inflammatory skin processes.

PMID- 1979592
TI  - Determination of erythrocyte glutathione peroxidase activity and its reference
      range in Chinese adults.
AB  - A method to assess selenium status of the body by measuring glutathione
      peroxidase activity in erythrocytes was studied. Reaction was measured by
      continuous monitoring of the decrease of NADPH at 340 nm. The erythrocyte
      glutathione peroxidase activity was determined at 37 degrees C, pH 7.5 by using
      one of the substrates, t-butyl hydroperoxide, to initiate the reaction, and using
      glutathione reductase as the coupling enzyme. The Km of the enzyme for
      glutathione and t-butyl hydroperoxide were determined to be 1.8 mM and 238
      microM, respectively. The enzyme was stable at -20 degrees C or -70 degrees C for
      at least 5 months, and for at least 2 months when stored at 4 degrees C. The
      within-run and between-run coefficients of variation for this method were 3.3
      4.9% and 3.0-7.1%, respectively. The test was linear up to 100 U/g hemoglobin,
      and had a sensitivity of 0.002 delta A/min at 3 U/L. The reference range of
      erythrocyte glutathione peroxidase in Chinese adults was estimated to be 28.6
      87.8 U/g hemoglobin (n = 84), without a significant difference in the results
      between males and females.

PMID- 1979591
TI  - Constitutive expression of a groEL-related protein on the surface of human
      gamma/delta cells.
AB  - Rabbit antibodies to hsp58 (P1), the human homologue of the Escherichia coli
      stress protein groEL, react specifically in indirect immunofluorescence and
      complement-dependent microcytoxicity experiments with a cell surface antigen
      expressed constitutively by T cell lines bearing gamma/delta receptors. This anti
      hsp58-reactive antigen is not demonstrable on T cells that express alpha/beta
      receptors or on various cells that lack T cell receptors. Certain evidence was
      obtained to suggest that the target antigen on the surface of gamma/delta T cells
      is a approximately 77-kD protein distinct from intracellular hsp58 and known
      members of the hsp70 stress protein family. While the exact nature and
      significance of this anti-hsp58-reactive protein remain to be determined, these
      data may help to clarify the roles of groEL-related stress proteins and
      gamma/delta cells that recognize groEL homologous in immunologic defense against
      infection and in autoimmune disease.

PMID- 1979593
TI  - Human leukocyte antigens in inhabitants of Taiwan.
AB  - Human leukocyte antigens (HLA) were investigated in 200 healthy Taiwan
      inhabitants of Taiwanese (46 persons), Hakka (36), Tai-Ya Tribe (28) Pu-Long
      Tribe (30) Pai-Wan Tribe (30) and Lu-kai (30) descent. In those of Taiwanese and
      Hakka descent, HLA-A11 and A2 were the two most frequently seen human leukocyte
      antigens. HLA-A11 was seen in 69.6% in those of Taiwanese descent and 61.1% in
      those of Hakka descent. HLA-A2 was seen in 50.0% of the Taiwanese and 44.4% of
      the Hakka. For the B loci, B40 (Taiwanese, 43.5%; Hakka, 44.4%), Bw46 (Taiwanese,
      28.3%; Hakka, 19.4%) and B13 (Taiwanese, 15.2%; Hakka, 30.6%) were the most
      common antigens. For the C loci, Cw3 (Taiwanese, 57.1%; Hakka 64.9%), Cw1
      (Taiwanese, 28.6%; Hakka, 35.1%) and Cw7 (Taiwanese, 40.5%; Hakka, 29.9%) were
      commonly seen antigens. The most commonly detected antigens for the DR loci were:
      DR2 (Taiwanese, 45.1%; Hakka, 56.8%) and DR4 (Taiwanese, 37.3%; Hakka, 32.4%).
      These results disclose that no major human leukocyte antigenic differences exist
      between the two aforementioned groups in this study. In addition, there are no
      major differences in Taiwanese and Hakka descent, and those of south and north
      mainland Chinese descent. All bear some antigenic similarities. However, for
      aborigines, the original inhabitants of Taiwan, the HLA antigens are
      significantly different from the Han Chinese as a whole. Characteristic features
      are seen in A24, Bw60, DRw6 and DRw8. In the meantime, a high frequency of common
      antigens are shared among the tribes and consequently a large number of blank
      alleles are seen in the aborigines. This reflects the homozygosity effect which
      is often seen in an isolated society.

PMID- 1979590
TI  - Tumor necrosis factor alpha activates soluble guanylate cyclase in bovine
      glomerular mesangial cells via an L-arginine-dependent mechanism.
AB  - Endothelium-derived nitric oxide (NO) causes vasodilatation by activating soluble
      guanylate cyclase, and glomerular mesangial cells respond to NO with elevations
      of intracellular guanosine 3',5'-cyclic monophosphate (cGMP). We explored whether
      mesangial cells can be stimulated to produce NO and whether NO modulates
      mesangial cell function in an autocrine or paracrine fashion. Tumor necrosis
      factor alpha (TNF-alpha) raised mesangial cell cGMP levels in a time- and
      concentration-dependent manner (threshold dose 1 ng/ml, IC50 13.8 ng/ml, maximal
      response 100 ng/ml). TNF-alpha-induced increases in mesangial cGMP content were
      evident at 8 h and maximal at 18-24 h. The TNF-alpha-induced stimulation of
      mesangial cell cGMP production was abrogated by actinomycin D or cycloheximide
      suggesting dependence on new RNA or protein synthesis. Hemoglobin and methylene
      blue, both known to inhibit NO action, dramatically reduced TNF-alpha-induced
      mesangial cell cGMP production. Superoxide dismutase, known to potentiate NO
      action, augmented the TNF-alpha-induced effect. Ng-monomethyl-L-arginine (L-NMMA)
      decreased cGMP levels in TNF-alpha-treated, but not vehicle-treated mesangial
      cells in a concentration-dependent manner (IC50 53 microM). L-arginine had no
      effect on cGMP levels in control or TNF-alpha-treated mesangial cells but
      reversed L-NMMA-induced inhibition. Interleukin 1 beta and lipopolysaccharide
      (LPS), but not interferon gamma, also increased mesangial cell cGMP content.
      Transforming growth factor beta 1 blunted the mesangial cell response to TNF
      alpha. TNF-alpha-induced L-arginine-dependent increases in cGMP were also evident
      in bovine renal artery vascular smooth muscle cells, COS-1 cells, and 1502 human
      fibroblasts. These findings suggest that TNF-alpha induces expression in
      mesangial cell of an enzyme(s) involved in the formation of L-arginine-derived
      NO. Moreover, the data indicate that NO acts in an autocrine and paracrine
      fashion to activate mesangial cell soluble guanylate cyclase. Cytokine-induced
      formation of NO in mesangial and vascular smooth muscle cells may be implicated
      in the pathogenesis of septic shock.

PMID- 1979594
TI  - Restriction fragment length polymorphism study of families with congenital
      adrenal hyperplasia due to 21-hydroxylase deficiency in Taiwan.
AB  - Congenital adrenal hyperplasia (CAH) is a heterogeneous group of hereditary
      diseases characterized by deficient adrenal cortisol synthesis. Most CAH is due
      to 21-hydroxylase (C21) deficiency. Genomic DNA from several families with 21
      hydroxylase deficiency and normal controls was analyzed by the Southern blot
      hybridization technique. The restriction fragment length polymorphism (RFLP)
      patterns using several endonucleases, such as Taq I, Eco RI and Pvu II, at the
      C21 gene locus showed a very low frequency of variability in normals and most of
      the patients with CAH. One proband with CAH lacked the characteristic 3.7 kb Taq
      I fragment probed with C21 cDNA. This may be due to gene conversion and/or
      deletion events in the functional C21 gene locus. On the other hand, genes
      closely linked to the C21 locus such as C4 and HLA-DR are highly polymorphic.
      Using these flanking genes as probes, it is easy to perform linkage analysis and
      identify the inheritance trait. Prenatal diagnosis will be possible in these
      affected families when an additional pregnancy is expected.

PMID- 1979595
TI  - Early effects of cranial irradiation on hypothalamic pituitary function.
AB  - Hypothalamic pituitary functions were studied in 25 patients before and 6 months
      after cranial irradiation with or without radiosensitizing chemotherapy for
      nasopharyngeal carcinoma. The estimated average total dose was 5,000 cGy to the
      hypothalamus and pituitary gland. The radiosensitizing chemotherapy used was
      endoxan, 4900 +/- 873 mg and/or methotrexate 113 +/- 30 mg. All patients had
      normal pituitary function before radiotherapy. Six months after radiotherapy,
      there was a significant increase in baseline serum thyrotropin (TSH) and follicle
      stimulating hormone (FSH) levels. The TSH response to thyrotropin-releasing
      hormone (TRH) was significantly increased, suggesting primary hypothyroidism due
      to neck irradiation. The peak serum TSH response to TRH became delayed in 21
      patients, suggesting a defect in TRH release. In male patients who did not
      receive radiosensitizing chemotherapy, the FSH response to luteotropic hormone
      releasing hormone (LHRH) increased while the luteinizing hormone (LH) response
      decreased. But in male patients who also received radiosensitizing chemotherapy,
      both the FSH and LH responses to LHRH increased. The adrenocorticotropic hormone
      (ACTH) response to ovine corticotropin-releasing hormone (CRH) did not change,
      while the integrated cortisol response increased. The growth hormone (GH)
      response to growth hormone-releasing hormone (GRH) did not change. The GH
      response to insulin tolerance test (ITT) increased and may be explained by the
      more severe hypoglycemia induced by the same dosage of insulin after radiotherapy
      or the recovery from the previous wasting caused by radiotherapy. There was no
      significant increase in serum prolactin. In conclusion, we demonstrated
      impairment of the hypothalamus-pituitary-endocrine gland axes as early as 6
      months after cranial irradiation with or without chemotherapy.

PMID- 1979596
TI  - Hypercalcemia in squamous cell carcinoma of the head and neck.
AB  - In a consecutive series of 771 patients with pathologically verified squamous
      cell carcinoma of the head and neck, 28 patients (3.6%) had hypercalcemia
      (greater than 11.0 mg/dl) during the course of their disease. The buccal mucosa
      (16/205, 7.8%) and tongue (8/148, 5.4%) were the most frequent primary sites.
      Most of the patients were stage IV patients with recurrence and advanced disease.
      The prognosis was poor with a median survival of only 6 weeks. The possible
      etiology of their hypercalcemia included humoral factors, bone metastases and
      independent primary lung cancer. The treatment of hypercalcemia was evaluated in
      22 patients. Success was noted in all patients initially receiving chemotherapy
      (10 cases) or radiotherapy (3 cases) with or without saline hydration plus
      furosemide diuretics. However, the response rate in patients (9 cases) initially
      receiving hydration plus furosemide diuretics alone was 22% (2/9), with 4 of 7
      failure cases later responding to chemotherapy. It is suggested that
      hypercalcemia be treated with chemotherapy or radiotherapy quickly, along with
      hydration plus diuretics. Also, the serum calcium level must be checked in
      patients with advanced buccal or tongue cancer.

PMID- 1979597
TI  - Radiotherapy for locally recurrent breast cancer.
AB  - A total of 43 breast cancer patients were treated at the Department of Radiation
      Oncology, Mackay Memorial Hospital from January 1978 to December 1987 for
      postoperative local-regional recurrence. Twenty-six patients developed local
      recurrence within 12 months after surgery and 17 patients developed local
      recurrence after 12 months. The mean age for this group of patients was 52 years
      (range: 27-82). There were 26 postmenopausal and 17 premenopausal patients.
      Twenty-four patients had received chemotherapy with cyclophosphamide,
      methotrexate and 5-fluorouracil (CMF) regimen. Four patients were excluded from
      this study due to incompletion of radiotherapy. Sites of local recurrence in the
      remaining 39 patients included: chest wall, single (8) and multiple (4); axilla
      (7); supraclavicular area (5); chest wall with regional node (11); and multiple
      regional nodes (4). All were free of distant metastasis at the initiation of
      radiotherapy. A mean tumor dose of 5000 cGy in 28 fractions was given over a 6
      week period to the chest wall and draining lymphatics, using an AECL Theratron 80
      or a CGR Alcyon MEV Cobalt-60 unit. The overall local control rate was 72%, and
      the 5-year local control rate was 59%. Nine patients experienced a second local
      recurrence, with a median interval of 8 months after radiotherapy. Four of them
      (4/9) also showed evidence of systemic disease at the same time. Distant
      metastasis, the major cause of mortality, appeared in 49% of the patients with a
      median interval of 22.8 months after radiotherapy. The three leading sites of
      distant metastasis were the bones (42%), lungs (37%) and liver (16%).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1979598
TI  - Hemodynamic significance of vectorcardiographic pattern in patients with mitral
      stenosis.
AB  - Vectorcardiographic (VCG) studies were conducted in 71 patients with pure mitral
      stenosis (MS) documented by clinical findings, echocardiograms and cardiac
      catheterization. Among them, 31 were males and 40 females, with ages ranging from
      20 to 58 (mean age 36.3) years. The Frank lead system was adopted for the VCG
      study. By VCG, 67 patients (94.4%) showed right ventricular hypertrophy (RVH),
      among whom 15 (21.2%) were type A, 30 (42.3%) type B and 22 (31.0%) type C. Forty
      five patients (63.4%) were in sinus rhythm (NSR), while the remaining 26 (36.6%)
      were in atrial fibrillation (AF). Patients with type A RVH had a significantly
      higher pulmonary wedge (PAW) and main pulmonary arterial (MPA) pressures than
      those with type B or C. Patients with type C had a higher mean MPA pressure (39.0
      +/- 11.3 mmHg) than those with type B (32.3 +/- 10.1 mmHg) (p less than 0.05).
      Among the 3 types of RVH, the mean right atrial (RA) pressures were similar (p
      greater than 0.05). Patients with AF had a lower mean MPA pressure, but a higher
      RA pressure than those with NSR (p less than 0.05). The maximal anterior force
      and maximal rightward force at the horizontal plane were significantly correlated
      with the mean MPA pressure (r = 0.54 and 0.49, respectively, both p less than
      0.01), but they did not correlated well with the PAW and RA pressures (p greater
      than 0.05). We conclude that in patients with MS, as pulmonary hypertension
      progresses, VCG seems to begin with type B RVH, then emerges into type C and
      finally becomes type A.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1979599
TI  - Pyogenic liver abscess: clinical manifestations and value of percutaneous
      catheter drainage treatment.
AB  - One hundred and sixty-two patients with solitary or multiple pyogenic liver
      abscesses received surgical or medical treatment in the past 8 years. Fifty-seven
      patients were treated medically (medical group), 62 patients received medical
      treatment plus sonogram-guided percutaneous drainage (PCD group), and 43 patients
      received surgical drainage (surgical group). Aerobic gram-negative rods were the
      predominant causative microorganisms. Klebsiella pneumoniae was the most common
      microorganism, occurring in 46.9% (76/162) of the cases. Anaerobes occurred in
      16.7% (27/162) of the cases. In the evaluation of treatment, the success rates
      for these three groups were: medical group, 59.6% (34/57); PCD group, 90.3%
      (56/62); and surgical group, 83.7% (36/43). This retrospective study confirms
      evidence from a small series that medical treatment plus percutaneous catheter
      drainage is efficient and more convenient than conventional surgical drainage for
      pyogenic liver abscesses. The frequent severe septic emboli to distant organs
      noted in this series (11.1%; 18/162) are quite unusual and should be anticipated
      in the future.

PMID- 1979600
TI  - Metabolic evaluation of urolithiasis.
AB  - After detailed instruction, 62 patients with urolithiasis treated at Taichung
      Veterans General Hospital entered this program, which ran from September 1987 to
      November 1988. Based on Pak's classification, there were 13 cases (21.0%) of
      absorptive hypercalciuria, type I (AH-I); 12 cases (19.4%) of absorptive
      hypercalciuria, type II (AH-II); 16 cases (25.8%) of renal hypercalciuria (RH); 3
      cases (4.8%) of hyperuricosuric calcium urolithiasis (HUCU); 11 cases (17.7%) of
      hypocitraturia (Hypocit); 3 cases (4.8%) of hyperoxluria (HO); one case (1.6%) of
      primary hyperparathyroidism (PHPT) and one case (1.6%) of infectious lithiasis.
      Two cases (3.2%) with no metabolic abnormalities were found. Hypocitraturia,
      HUCU, and HO can be the primary abnormal findings, but more often coexist with
      various forms of hypercalciuria as a second factor. If the coexistence is
      considered, hypocitraturia (33 cases, 53.2%) and HUCU (24 cases, 38.7%) were the
      most prevalent categories. Meanwhile, 24 cases (38.7%) had only one physiological
      derangement, 25 cases (40.3%) had two derangements, and 13 cases (21.0%) had
      three. This study indicates that metabolic evaluation can elucidate the
      physiological derangements of urolithiasis, so that further medical treatment can
      be administered selectively.

PMID- 1979601
TI  - Thoracic spondylosis: experience of 4 cases.
AB  - Thoracic spondylosis is relatively uncommon compared to cervical or lumbar
      spondylosis. It may cause spinal canal stenosis and result in radiculopathy,
      neurogenic claudication, and most commonly, myelopathy. We present our experience
      in the management of 4 cases with symptomatic thoracic spondylosis. The lower
      thoracic spine was involved in all 4 cases. The pathological changes are almost
      the same as in cervical or lumbar spondylosis except that ossification of
      ligamenta flava is more common in thoracic spondylosis. The ossified ligamenta
      flava may adhere tightly to the dura mater, and therefore increase the difficulty
      of operation. The results of decompressive laminectomy for thoracic spondylosis
      were acceptable.

PMID- 1979602
TI  - Congenital spinal arachnoid cysts: report of 2 cases with review of the
      literature.
AB  - Two cases of congenital spinal arachnoid cysts with paraparesis are presented.
      Case 1, a 16-year-old male patient, had a 2-year history of progressive weakness
      of the lower limbs. Postmyelographic axial computed tomography (CT) and
      myelography revealed a dorsally located extradural mass. The configuration of the
      mass was further assessed with magnetic resonance imaging (MRI). He underwent
      laminectomy from T8 to L1 with total excision of an extradural arachnoid cyst. A
      communication with the subarachnoid space found at the T8 level was surgically
      closed. The patient made an uneventful recovery. Case 2, a 9-year-old girl,
      developed paraparesis and the cauda equina syndrome two days prior to admission.
      Postmyelographic CT and myelography revealed an anteriorly located intradural
      mass. She underwent laminectomy from C6 to T2 and partial removal of an
      intradural arachnoid cyst. One week later, her neurological functions had
      recovered completely. The literature dealing with this rare spinal lesion is also
      reviewed.

PMID- 1979603
TI  - Neurinoma of the spinal accessory nerve: report of a case.
AB  - We report a patient with neurinoma of the spinal accessory nerve, who complained
      of intermittent occipital headaches, nausea, vomiting, blurred vision and
      unsteady gait. Neurological examination revealed papilledema, bilateral
      horizontal nystagmus and right cerebellar signs. Computed tomography revealed
      mild hydrocephalus, a low-attenuated lesion with a faint capsule after
      enhancement and partial compression of the 4th ventricle in the right posterior
      fossa. Vertebral angiography revealed no definite tumor vessels or stains. Under
      the impression of a posterior fossa tumor, a suboccipital craniectomy with a C1
      and C2 laminectomy was performed. A 4 x 4 x 2.5 cm3 dumbbell tumor arising from
      the left spinal accessory nerve at the C2 level was found 4 x 4 x 2.5 cm3. The
      tumor extended upward through the foramen magnum with upward displacement of both
      tonsils to the right jugular foramen with slight adhesion to the right IX, X and
      XI cranial nerves. The left spinal accessory nerve was severed from the pedicle
      at the C2 level, and the tumor was totally removed. Diagnosis was made during the
      operation. The pathological examination showed neurinoma with cystic
      degeneration. During the following year, atrophy of the left sternocleidomastoid
      and trapezius muscles were noticed. Up to the time of this writing, there had
      been no clinical recurrence.

PMID- 1979604
TI  - Continuous blood glucose monitoring with feedback-controlled glucose infusion
      during surgical management of insulinoma: report of a case.
AB  - Perioperative management of insulinoma may be facilitated by the use of a glucose
      controlled insulin infusion system (GCIIS; Biostator System, Miles Laboratories
      Inc., Elkhart, Ind.). We monitored the blood glucose levels and glucose infusion
      rates before, during and after surgery in a 35-year-old woman with insulinoma.
      After an overnight fast, glucose was infused according to a preset program and
      maintained the blood glucose level at around 50 mg/dl. Depression of the blood
      glucose level and simultaneous elevation of the glucose infusion rate were noted
      when the tumor was massaged. A sharp decrease in the glucose infusion rate
      occurred almost immediately after removal of the tumor. It took about 4 minutes
      for the blood glucose to go up to a level of 90 mg/dl. These results demonstrate
      the usefulness of GCIIS not only in maintaining stationary blood glucose, but
      also in localizing the tumor and in providing evidence of complete removal of the
      tumor. When the infusion system is programmed appropriately, the glucose infusion
      rate, as compared to the blood glucose level, reacts more quickly and sensitively
      to sudden changes in insulin levels.

PMID- 1979605
TI  - A technique using V-shaped transmural suture fixation in percutaneous endoscopic
      gastrostomy.
AB  - A new method of percutaneous endoscopic gastrostomy (PEG) using V-shaped
      transmural suture fixation was performed on 2 patients with advanced carcinoma.
      This method secures the gastrostoma in a way superior to the conventional
      technique. It facilitates exchange of the catheter and avoids potential morbidity
      caused by peritoneal leakage even when tube feeding has been initiated in the
      early post-insertion stage. Inadvertent complications of hematoma formation and
      necrotizing fasciitis can also be prevented.

PMID- 1979606
TI  - [Psychosocial aspect of somatic complaints in patients after myocardial
      infarction].
AB  - The aim of this study was to explore the association between psychosocial
      variables and somatic complaints in terms of the biopsychosocial model. The
      analysis showed that both socioeconomic and psychological variables play a
      prominent role in the subjective complaints of coronary symptoms as follows: (1)
      Functional class: A low occupational index was found to be a predictor of much
      disability. Subjects with higher self-ratings of psychiatric symptoms (i.e.
      phobia, depression, interpersonal hypersensitivity), lower personal well-being
      (i.e. esteem, competence), and major social maladaptation had significantly more
      disability. (2) Chest pain: Patients with a higher morbidity of chest pain were
      more likely to be female, have less education, have more social maladjustment,
      and have less social support. Higher scores of psychiatric symptoms (i.e.
      anxiety, depression, hostility) and a perception of threatening by others were
      highly correlated with the severity of chest discomfort. Physicians should be
      aware of the ways in which psychosocial and biomedical variables may interact at
      many levels, especially for the patients with unexplained physical symptoms or
      social dysfunction.

PMID- 1979607
TI  - [Utilization and medical cost of patients with different insurance coverage among
      group practice centers].
AB  - In order to explore the utilization and medical cost of patients with different
      insurance coverage in group practice centers, we collected patient data in three
      centers from September 1, 1987 to February 28, 1988. We classified the payments
      as self-payment,partial-reimbursement and total-reimbursement. There were 42,234
      visits by 8,111 patients. The average frequency of visits within 6 months was 6.1
      in total-reimbursement patients, 5.2 in partial-reimbursement patients and 2.6 in
      self-payment patients. We found that the frequency of visits increased with age
      in patients with total-reimbursement and partial-reimbursement. On the other
      hand, the frequency decreased after the age of 65 in patients with self-payment;
      whether it was related to the economic problems of the elderly needs further
      study. The highest medical cost per visit was NT$. 343 in total reimbursement
      patients, followed by NT$. 281 in partial-reimbursement patients. The lowest cost
      was NT$. 208 in self-payment patients. Yet, the highest ratio of total drug cost
      by total medical cost per visit was 73.7% in partial-reimbursement patients
      followed by 63.6% in total-reimbursement patients. The lowest ratio was 56.7% in
      self-payment patients. Although the partial-reimbursement system could not
      decrease the ratio of total drug cost by total medical cost per visit, it would
      be beneficial in group practice centers to decrease the patients' visits and the
      medical cost per visit. Therefore, this system should be executed in the future.

PMID- 1979608
TI  - [Progressive supranuclear palsy: clinical report on 7 cases and review of
      literature].
AB  - Progressive supranuclear palsy is sufficiently rare and difficult to diagnose
      that it escaped clinical recognition until 1964, when Steele, Richardson, and
      Olszewski clarified it as a pathologic entity. From January 1981 to June 1989, 7
      patients who fulfilled the Golbe's criteria of progressive supranuclear palsy
      were admitted to the neurological department of National Taiwan University
      Hospital. The mean age at onset was 60 years (range: 53-69 years), and the mean
      age at diagnosis was 63 years), and the mean age at diagnosis was 63 years
      (range: 55-71 years). The study failed to identify any specific risk factors
      associated with progressive supranuclear palsy. Unsteady gait, vertical gaze
      palsy, pseudobulbar palsy, parkinsonian features and dementia were noted in all
      cases. The brain computed tomography revealed mild cortical atrophy and
      ventricular dilatation in 5 patients. Additionally, electroencephalography
      revealed diffuse theta waves in 4 patients and temporal theta waves in 2
      patients, but these findings were nonspecific. Nystagmograms were performed in 3
      patients, and hypometric saccades were noted in all of these patients, and
      uninhibited neurogenic bladder was proven by cystometry in 2 of these patients.
      All patients were treated with levodopa, but none of the patients showed any
      beneficial effects. Two patients died of aspiration pneumonia; the average
      duration from onset to death was about 4 years.

PMID- 1979610
TI  - Metamorphosis of the central nervous system of Drosophila.
AB  - The study of the metamorphosis of the central nervous system of Drosophila
      focused on the ventral CNS. Many larval neurons are conserved through
      metamorphosis but they show pronounced remodeling of both central and peripheral
      processes. In general, transmitter expression appears to be conserved through
      metamorphosis but there are some examples of possible changes. Large numbers of
      new, adult-specific neurons are added to this basic complement of persisting
      larval cells. These cells are produced during larval life by embryonic
      neuroblasts that had persisted into the larval stage. These new neurons arrest
      their development soon after their birth but then mature into functional neurons
      during metamorphosis. Programmed cell death is also important for sculpting the
      adult CNS. One round of cell death occurs shortly after pupariation and a second
      one after the emergence of the adult fly.

PMID- 1979611
TI  - 1990 American Paraplegic Society (APS) annual conference abstract presentations.

PMID- 1979612
TI  - Electrophysiological studies of acetylcholine and the role of the basal forebrain
      in the somatosensory cortex of the cat. I. Cortical neurons excited by glutamate.
AB  - 1. Microelectrodes attached to iontophoretic pipettes were used to isolate 410
      single neurons in the primary somatosensory cortex of halothane-anesthetized
      cats. Basal forebrain (BF) stimulation, when paired with pulses of
      iontophoretically administered glutamate, affected the responsiveness in 24 (54%)
      of 39 neurons; 17 were facilitated, and seven were inhibited. Five minutes after
      BF stimulation the average response for a sample of 20 cells was enhanced by 45%
      (+/- 19). All but one of the effects lasted as long as the cell was studied,
      often greater than 1 h. 2. When atropine was administered while the BF was
      stimulated during glutamate excitation, 7 of 16 cells were enhanced, but the
      average increase was only 16% (+/- 15) for a sample of 15 cells. After the
      atropine had dissipated, four cells were enhanced by the BF stimulus. In three of
      these the enhancement had been blocked previously by atropine. 3. BF stimulation
      had effects similar to iontophoretically administered acetylcholine (ACh), but
      the effects appeared more frequently with BF stimulation than they had with
      acetylcholine administration. 4. We propose that the enhanced neuronal
      responsiveness is due to the release of acetylcholine by cortical terminals of
      cholinergic neurons located in the BF. The BF stimulus may be more effective than
      acetylcholine administration because corticopetal cholinergic fibers may end in
      the immediate vicinity of receptors responsible for long-term changes in membrane
      permeability.

PMID- 1979609
TI  - Regulation of the formation and water permeability of endosomes from toad bladder
      granular cells.
AB  - Osmotic water permeability (Pf) in toad bladder is regulated by the vasopressin
      (VP)-dependent movement of vesicles containing water channels between the
      cytoplasm and apical membrane of granular cells. Apical endosomes formed in the
      presence of serosal VP have the highest Pf of any biological or artificial
      membrane (Shi and Verkman. 1989. J. Gen. Physiol. 94:1101-1115). We examine here:
      (a) the influence of protein kinase A and C effectors on transepithelial Pf
      (Pfte) in intact bladders and on the number and Pf of labeled endosomes, and (b)
      whether endosome Pf can be modified physically or biochemically. In paired
      hemibladder studies, Pfte induced by maximal serosal VP (50 mU/ml, 0.03 cm/s) was
      not different than that induced by 8-Br-cAMP (1 mM), forskolin (50 microM), VP +
      8-Br-cAMP, or VP + forskolin. Pf was measured in endosomes labeled in intact
      bladders with carboxyfluorescein by a stopped-flow, fluorescence-quenching assay
      using an isolated microsomal suspension; the number and Pf (0.08-0.11 cm/s, 18
      degrees C) of labeled endosomes was not different in bladders treated with VP,
      forskolin, and 8-Br-cAMP. Protein kinase C activation by 1 microM mucosal phorbol
      myristate acetate (PMA) induced submaximal bladder Pfte (0.015 cm/s) and endosome
      Pf (0.022 cm/s) in the absence of VP, but had little effect on maximal Pfte and
      endosome Pf induced by VP. However, PMA increased by threefold the number of
      apical endosomes with high Pf formed in response to serosal VP. Pf of endosomes
      containing the VP-sensitive water channel decreased fourfold by increasing
      membrane fluidity with hexanol or chloroform (0-75 mM); Pf of phosphatidylcholine
      liposomes (0.002 cm/s) increased 2.5-fold under the same conditions. Endosome Pf
      was mildly pH dependent, strongly inhibited by HgCl2, but not significantly
      altered by GTP gamma S, Ca, ATP + protein kinase A, and phosphatase action. We
      conclude that: (a) water channels cycled in endocytic vesicles are functional and
      not subject to physiological regulation, (b) VP and forskolin do not have cAMP
      independent cellular actions, (c) activation of protein kinase C stimulates
      trafficking of water channels, but does not increase the number of apical
      membrane water channels induced by maximal VP, and (d) water channel function is
      sensitive to membrane fluidity. By using VP and PMA together, large quantities of
      endosomes containing the VP-sensitive water channel are labeled with fluid-phase
      endocytic markers.

PMID- 1979614
TI  - Comparative studies in hypertension. Report of a symposium. Titisee-Neustadt,
      Germany, 7-9 September 1989. Proceedings.

PMID- 1979613
TI  - Excitatory postsynaptic potentials in rat neocortical neurons in vitro. III.
      Effects of a quinoxalinedione non-NMDA receptor antagonist.
AB  - 1. Intracellular microelectrodes were used to obtain recordings from neurons in
      layer II/III of rat frontal cortex. A bipolar electrode positioned in layer IV of
      the neocortex was used to evoke postsynaptic potentials. Graded series of
      stimulation were employed to selectively activate different classes of
      postsynaptic responses. The sensitivity of postsynaptic potentials and
      iontophoretically applied neurotransmitters to the non-N-methyl-D-asparate (NMDA)
      antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) was examined. 2. As
      reported previously, low-intensity electrical stimulation of cortical layer IV
      evoked short-latency early excitatory postsynaptic potentials (eEPSPs) in layer
      II/III neurons. CNQX reversibly antagonized eEPSPs in a dose-dependent manner.
      Stimulation at intensities just subthreshold for activation of inhibitory
      postsynaptic potentials (IPSPs) produced long-latency (10 to 40-ms) EPSPs (late
      EPSPs or 1EPSPs). CNQX was effective in blocking 1EPSPs. 3. With the use of
      stimulus intensities at or just below threshold for evoking an action potential,
      complex synaptic potentials consisting of EPSP-IPSP sequences were observed. Both
      early, Cl(-)-dependent and late, K(+)-dependent IPSPs were reduced by CNQX. This
      effect was reversible on washing. This disinhibition could lead to enhanced
      excitability in the presence of CNQX. 4. Iontophoretic application of quisqualate
      produced a membrane depolarization with superimposed action potentials, whereas
      NMDA depolarized the membrane potential and evoked bursts of action potentials.
      At concentrations up to 5 microM, CNQX selectively antagonized quisqualate
      responses. NMDA responses were reduced by 10 microM CNQX. D-Serine (0.5-2 mM), an
      agonist at the glycine regulatory site on the NMDA receptor, reversed the CNQX
      depression of NMDA responses.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1979615
TI  - Casual versus ambulatory twenty-four-hour blood pressure measurement in a
      comparative study with bisoprolol or nitrendipine.
AB  - In a double-blind, placebo-controlled, randomly allocated study, the 24-h
      efficacy of a single morning dose of 10 mg of the beta-blocker bisoprolol (n =
      17) versus 20 mg of the calcium channel antagonist nitrendipine (n = 19) was
      assessed using two different methods of blood pressure determination: (1) casual
      blood pressure determinations in the morning before the dose; and (2) ambulatory
      day-time (6 a.m. to 6 p.m.) and night-time (6 p.m. to 6 a.m.) blood pressure
      monitoring using a non-invasive automatic device (Spacelabs 90202). After 4 weeks
      both agents induced significant blood pressure reductions compared to the placebo
      period as assessed by both casual and ambulatory day-time readings, without
      significant differences in the blood pressure reductions induced by the two drugs
      (P less than 0.05). Ambulatory night-time values, however, showed a significant
      blood pressure reduction only for bisoprolol (from 138 +/- 16/84 +/- 12 to 129 +/
      15/77 +/- 11 mmHg); nitrendipine did not induce any significant systolic or
      diastolic blood pressure changes during this period (140 +/- 11/87 +/- 10 to 136
      +/- 13/86 +/- 10 mmHg). Individual response rates were 47% for nitrendipine and
      71% for bisoprolol. The incidence of side effects was comparable under both
      drugs. Our results indicate that bisoprolol was more effective over 24 h than
      nitrendipine. We also conclude that the value of casual blood pressure readings
      for the evaluation of therapeutic agents given once a day seems to be limited in
      comparison to 24-h ambulatory monitoring.

PMID- 1979616
TI  - Uncultured lobster muscle, cultured neurons and brain slices: the neurophysiology
      of zinc.

PMID- 1979617
TI  - Comparison of calculated and experimentally determined punch displacement on a
      rotary tablet press using both Manesty and IPT punches.
AB  - An indirect method of calculating punch displacement on a rotary tablet press
      from measurements of the change in punch force with the turret position was in
      good agreement with direct measurements of punch displacement made using a linear
      variable displacement transducer (LVDT)-slip ring system. The direct measurements
      were made during the compaction of three direct compression agents using Manesty
      punches. However, the agreement between calculated and experimentally determined
      punch displacements was unsatisfactory when IPT punches were used. The IPT
      punches have a much flatter punch head profile than the Manesty punches. Due to
      this difference, the analytic equation does not accurately describe the dynamics
      of the press under normal operating conditions. Terms in the analytic equation,
      determined originally under static conditions, were re-evaluated under dynamic
      conditions for both sets of tooling using the LVDT-slip ring system. Excellent
      agreement for both IPT and Manesty punches was found between punch displacement
      calculated using the revised analytic equation and direct experimental
      measurements. Punch displacements determined from punch head profile and machine
      geometry only, without taking machine deformations into account, were shown to
      differ widely from the calculated and experimental values.

PMID- 1979618
TI  - Stability of liposomes on long term storage.
AB  - The effect of the lipid composition of liposomes on their storage for up to one
      year under different environmental conditions has been examined using 5,6
      carboxyfluorescein as a model drug. When cholesterol and/or alpha-tocopherol were
      included in the liposomes, a significantly greater amount of dye was retained.
      The presence of alpha-tocopherol decreased the breakdown of phosphatidylcholine
      to lysophosphatidylcholine and also reduced the level of peroxidation.
      Carboxyfluorescein retention was further enhanced when liposomes were stored at 4
      degrees C or at room temperature (20 degrees C) in an O2-free atmosphere.
      Lysophosphatidylcholine formation also slowed when the liposomes were kept at 4
      degrees C, or in an O2-free atmosphere. It is concluded that egg yolk lecithin
      liposomes may be stored for long periods at low temperature in an O2-free
      atmosphere or with added stabilizers such as cholesterol and alpha-tocopherol.

PMID- 1979619
TI  - Normal phase HPLC as a model system of specific benzodiazepine-receptor binding.
AB  - The hypothesis that benzodiazepines interact with their receptors in the CNS via
      hydrogen bonding mediated by the carbonyl and imine groups has been studied by
      correlating a physicochemical parameter affected by hydrogen bonds potentially
      accepted or donated by benzodiazepines with their binding constants to
      synaptosomal rat brain membranes. The reference physicochemical system chosen was
      normal phase high-performance liquid chromatography on mu-Bondapack NH2
      (propylamine groups chemically bonded to porous silica) eluted with mixtures of n
      hexane and 2-propanol. A strong correlation has been found for binding of the
      implicated groups to the column and to the receptor.

PMID- 1979620
TI  - Calcium antagonist properties of cinnarizine, trifluoperazine and verapamil in
      guinea-pig normal and skinned trachealis muscle.
AB  - In guinea-pig trachealis, depolarized by a K(+)-rich medium, Ca2+ (0.01-10 mM)
      caused concentration-related spasm. Verapamil (0.5-5 microM), cinnarizine (10-100
      microM) and trifluoperazine (16-160 microM) each produced concentration-dependent
      antagonism of Ca2+ characterized by a rightward and downward displacement of the
      log concentration-effect curve for Ca2+. The rank order of potencies of these
      antagonists, measured as the IC75 against Ca2+ (10 mM)-induced contraction of
      depolarized trachea, was verapamil (5.6 microM) greater than cinnarizine (59
      microM) greater than trifluoperazine (91 microM). In skinned trachea, verapamil
      in concentrations up to 100 microM did not modify the concentration-effect curve
      for Ca2+. In contrast, cinnarizine (59-177 microM) diminished the sensitivity and
      trifluoperazine (273 microM) decreased the responsiveness of the tissue to Ca2+.
      In skinned trachea, trifluoperazine (91 microM) produced greater inhibition of
      Ca2+ (10 microM)-induced contraction after 120 min than after 30 min of
      incubation. Verapamil (100 microM) and cinnarizine (177 microM) were devoid of
      inhibitory effect against the 10 microM Ca2+ standard. In skinned trachea,
      changes in the Ca2+ concentration-effect curve produced by cinnarizine (177
      microM) were reversed after washout whilst those induced by trifluoperazine (273
      microM) persisted. It is concluded that distinct differences exist between the
      three calcium antagonists examined. The action of verapamil is restricted to the
      plasmalemma. That of cinnarizine and trifluoperazine is exerted both on the
      plasma membrane and upon the intracellular contractile machinery.

PMID- 1979621
TI  - Some differential effects of 4-diphenylacetoxy-N-(2-chloroethyl)-piperidine
      hydrochloride on guinea-pig atria and ileum.
AB  - 4-Diphenylacetoxy-N-(2-chloroethyl)-piperidine hydrochloride (I) cyclizes at
      neutral pH to form an aziridinium salt. The formation and breakdown of the salt
      depend on the temperature (in the range 25 to 37 degrees C). In solution at 30
      degrees C, peak levels, corresponding to 60-80% conversion, are reached after
      around 60 min and the half-life exceeds 100 min. In the presence of 0.9% NaCl
      conversion was reduced to 45-60%. I blocks muscarinic receptors in guinea-pig
      ileum and atria irreversibly and it is possible to produce dose-ratios on ileum
      with 10 nM I which are about 100 times those on atria. After about 30 min
      exposure to solutions of I (prepared 15-20 min previously so that formation of
      aziridinium ions is well-established) the graph of log (dose-ratio) against time
      is linear and similar plots were obtained with two different agonists, carbachol
      and ethoxyethyltrimethylammonium. With results for the ileum, extrapolation of
      the line suggests that it does not start from zero (dose-ratio = 1): this is
      because of an initial relatively rapid reversible block. This early phase is
      similar to that seen on ileum with 10 nM 4DAMP methobromide, which is a
      competitive antagonist, so is probably caused by competitive block by the
      aziridinium ion, which closely resembles 4DAMP metho-salts. The subsequent
      irreversible phase should be caused by alkylation of the receptors. I is easy to
      make and should be a valuable tool for the study of muscarinic receptors.

PMID- 1979622
TI  - Effect of nipradilol on myocardial energy metabolism in the dog ischaemic heart.
AB  - The effect of nipradilol, a newly developed beta-adrenoceptor blocking agent with
      a vasodilatory action, on myocardial energy metabolism has been examined in the
      dog ischaemic heart, and compared with that of propranolol. Ischaemia was induced
      by ligating the left anterior descending coronary artery. Either saline,
      nipradilol (0.3 mg kg-1), or propranolol (1 mg kg-1) was injected intravenously 5
      min before coronary ligation. After 3 or 30 min of coronary ligation, the
      ischaemic region of the myocardium was removed, and the endocardial portion used
      to determine the levels of adenosine triphosphate (ATP), adenosine diphosphate
      (ADP), adenosine monophosphate (AMP), creatine phosphate (CrP) and lactate.
      Ischaemia decreased the levels of ATP and CrP, and increased the levels of ADP,
      AMP and lactate. Immediately after the injection of nipradilol, rapid falls in
      blood pressure and heart rate were observed. Pretreatment with nipradilol
      lessened the decreases in the levels of ATP and CrP and the increases in the
      levels of AMP and lactate, caused by 3 min of ischaemia, to the same extent as
      propranolol. However, after 30 min of ischaemia, nipradilol had no effect on
      myocardial metabolism unlike propranolol. These results indicate that nipradilol
      can reduce ischaemic influences on myocardial metabolism as well as propranolol,
      but only in the early stages of ischaemia.

PMID- 1979623
TI  - Augmented potentiation of renal vasoconstrictor responses by thromboxane A2
      receptor stimulation in the alloxan-diabetic rat.
AB  - Dose-response curves were obtained to bolus injections of noradrenaline (NA) and
      5-hydroxytryptamine (5-HT) in blood and Krebs-perfused kidneys of male Wistar
      rats. Vasoconstrictor responses to both NA and 5-HT were significantly attenuated
      in blood-perfused kidneys of alloxan-treated 14 day diabetic rats compared with
      non-diabetic animals. Responses to low doses of NA were also significantly
      attenuated in Krebs-perfused kidneys from diabetic rats but responses to 5-HT
      were augmented. Dose-dependent potentiation of vasoconstrictor responses to NA
      and 5-HT in Krebs-perfused kidneys of both non-diabetic and diabetic rats
      occurred during infusion of the thromboxane A2 (TxA2)-mimetic U46619 [15S)
      hydroxy-11 alpha, 9 alpha-(epoxymethano) prosta-5Z, 13E-dienoic acid). The
      potentiation by U46619 (11 ng mL-1) was inhibited in both groups during infusion
      of the thromboxane receptor antagonist AH23848 [( 1 alpha(Z), 2 beta, 5 alpha]
      (+/-)-7-[5[[(1,1'-biphenyl)-4-yl]methoxyl]-2-(4- morpholinyl)-3-oxocyclopentyl]-4
      heptenoic acid). Infusion of 5-HT in Krebs-perfused kidneys of non-diabetic rats,
      causing a rise in perfusion pressure of similar magnitude to that produced by
      infusion of 111ng mL-1 U46619, did not significantly affect responses to bolus
      injections of NA. Potentiation of vasoconstrictor responses to low concentrations
      of 5-HT by U46619 was significantly greater in Krebs-perfused kidneys of diabetic
      rats than kidneys from non-diabetic animals. Activation of vascular TxA2
      receptors augments the vasoconstrictor effects of 5-HT in Krebs-perfused diabetic
      rat kidneys to a greater extent than in non-diabetic kidneys.

PMID- 1979624
TI  - The effect of malaria infection on the disposition of quinine and quinidine in
      the rat isolated perfused liver preparation.
AB  - The effect of malaria on the disposition of quinine and quinidine was studied in
      livers isolated from young rats infected with merozoites of Plasmodium berghei, a
      rodent malaria model, and non-infected controls. Following bolus administration
      of quinine (1 mg) or quinidine (1 mg) to the 100 mL recycling perfusion circuit,
      perfusate was sampled (0-4 h) and plasma assayed for quinine and quinidine by
      HPLC. Higher quinine (AUC:6470 +/- 1101 vs 3822 +/- 347 ng h mL-1, P less than
      0.001) and quinidine (AUC: 6642 +/- 1304 vs 4808 +/- 872 ng h mL-1, P less than
      0.05) concentrations were observed during malaria infection (MI). MI resulted in
      decreased quinine clearance (CL) (0.33 +/- 0.08 vs 0.64 +/- 0.09 mL min-1 g-1, P
      less than 0.001) and volume of distribution (Vd) (53.0 +/- 13.3 vs 81.2 +/- 23.7
      mL g-1, P less than 0.05) but no significant change in elimination half-life
      (t1/2) (1.93 +/- 0.6 vs 1.37 +/- 0.25 h, P greater than 0.05). With quinidine,
      however, MI resulted in decreased CL (0.38 +/- 0.16 vs 0.64 +/- 0.09, P less than
      0.05) with no change in Vd and a significant increase in t1/2 (1.62 +/- 0.42 vs
      0.88 +/- 0.22, P less than 0.01). In summary, the hepatic disposition of quinine
      and quinidine is altered in the malaria-infected rat.

PMID- 1979625
TI  - The sorption of isosorbide-5-mononitrate to intravenous delivery systems.
AB  - The sorption of isosorbide-5-mononitrate, diluted in 0.9% NaCl or 10% glucose
      solutions, to intravenous delivery systems was investigated. Infusion bags,
      burettes, a syringe, infusion tubings and end-line filters were tested in static
      and in dynamic experiments. No clinically significant sorption was detected
      during those experiments. The use of PVC tubings of different hardness did not
      influence the results.

PMID- 1979626
TI  - Role of unstirred water layer in the exsorption of quinidine.
AB  - Intestinal ++exsorption of salicylic acid, thiopentone, theophylline, and
      quinidine was measured during perfusion of the intestinal lumen with Tyrode
      solution. The effect of pectin or bovine serum albumin added to the perfusate on
      intestinal clearance (CLi) was investigated. Increasing pectin concentration from
      0.0 to 0.5, 1.0 and 1.5% gave CLi values for quinidine of 499 +/- 18, 363 +/- 35,
      237 +/- 56, and 300 +/- 28 mL h-1 kg-1, respectively. One per cent of pectin in
      the perfusate also decreased the CLi of thiopentone, but had no effect on the CLi
      of salicylic acid or theophylline. Pectin may have increased the thickness of the
      unstirred water layer on the mucous membrane and the resistance of drug
      exsorption for some drugs. When bovine serum albumin was added, drug binding in
      the perfusate increased, and the CLi of salicylic acid, thiopentone, and
      theophylline increased; the CLi of quinidine was unaltered. Co-administration of
      theophylline with quinidine decreased the CLi of quinidine without affecting
      quinidine binding in serum or in the perfusate. The CLi theophylline was not
      affected by quinidine. These observations are consistent with the hypothesis that
      the exsorption of quinidine is rate-limited by diffusion through the unstirred
      water layer on the mucous membrane. The CLi of quinidine is affected by the
      microclimate-pH in the unstirred water layer. An alternative possibility is that
      quinidine exsorption is mediated by a carrier-transport pathway.

PMID- 1979627
TI  - The effect of nefopam and its enantiomers on the uptake of 5-hydroxytryptamine,
      noradrenaline and dopamine in crude rat brain synaptosomal preparations.
AB  - The effect of (+/-), (+) and (-)-nefopam on the uptake of 5-hydroxytryptamine (5
      HT), noradrenaline and dopamine in synaptosomal preparations from rat forebrain,
      hippocampus and striatum has been investigated. All three forms of nefopam
      inhibited the amine uptake in the investigated structures, the order of potency
      being (+) greater than (+/-) greater than (-). (+)-Nefopam was 7-30 times more
      potent than (-)-nefopam. The same order of potency has also been found for the
      antinociceptive effect of these three forms, however, the differences were
      smaller. Inhibition of 5-HT and noradrenaline uptake may not be the sole
      mechanism underlying the analgesic effect of nefopam.

PMID- 1979628
TI  - JO 1784, a potent and selective ligand for rat and mouse brain sigma-sites.
AB  - JO 1784 ((+)-cinnamyl-1-phenyl-1-N-methyl-N-cyclopropylene) is a potent ligand
      for (+)-[3H]SKF 10,047 (2'-hydroxy-5,9-dimethyl-2-allyl-6,7-benzomorphan) binding
      sites in rat brain membrane preparations with an IC50 of 39 +/- 8 nM, which is
      comparable to that of haloperidol. The stereoisomer of JO 1784 is ten fold less
      potent. When administered to mice i.p. or p.o. JO 1784 displaced (+)-[3H]SKF
      10,047 (5 muCi i.v.) from its sites in the brain with ID50 values of 1.2 and 3.5
      mg kg-1, respectively. The high selectivity of JO 1784 for the sigma-binding site
      was assessed by its lack of significant affinity for more than 20 other sites
      including those for phencyclidine.

PMID- 1979629
TI  - The effect of fatty acids on the rectal absorption of acyclovir in rats.
AB  - The enhancing effect of fatty acids on the rectal absorption of acyclovir has
      been evaluated in rats. Acyclovir proved to be absorbed to the extent of 3 to 9%
      after oral administration. After rectal administration in the absence of
      absorption-promoter, the bioavailability of acyclovir was 37%. Its rectal
      administration with 4% sodium caprate resulted in enhanced bioavailability (81 +/
      3%).

PMID- 1979630
TI  - Relaxant and beta 2-adrenoceptor blocking activities of (+/- )-, (+)- and (-)
      pindolol on the rat isolated aorta.
AB  - The KCl contracted rat aorta is relaxed by procaterol, (+/- )-, (+)- and (-)
      pindolol. The relaxations to procaterol, but not to (+/- )-pindolol, were
      prevented by ICI 118,551 at 10(-6) M. The relaxations to (+/- )-pindolol are,
      therefore, not due to beta-adrenoceptor agonism. At 10(-7) M ICI 118,551, (+/- )
      , (+)- and (-)-pindolol were beta 2-adrenoceptor antagonists as they inhibited
      the relaxant responses of the aorta to procaterol.

PMID- 1979631
TI  - Comparison of the inhibitory action of aminobeclamide and beclamide on socially
      offensive behaviour.
AB  - The inhibitory effects of aminobeclamide (N-(p-aminobenzyl)-beta
      chloropropionamide) on socially offensive behaviour has been studied and compared
      with those of the parent drug beclamide (N-benzyl-beta-chloropropionamide).
      Following oral administration in mice which had been individually housed for a 28
      day period then paired with normal group-housed opponents, aminobeclamide and
      beclamide both produced significant and dose-related inhibition of socially
      offensive behaviour. Aminobeclamide (20-150 mg kg-1 p.o.) and beclamide (50-250
      mg kg-1 p.o.) gave increased offense onset latency whilst at the same time they
      reduced the incidence of offense encounters/animal and decreased the group
      percentage of animals displaying offense behaviour. It is likely that both drugs
      have similar monoamine modifying effects though this animal study suggests that
      aminobeclamide is 1.5 to 2.7 times more potent than beclamide against socially
      offensive behaviour.

PMID- 1979632
TI  - A rapid gas-liquid chromatographic method for the determination of cotinine and
      nicotine in biological fluids.
AB  - A rapid method is described for the simultaneous measurement of nicotine and
      cotinine in biological fluids using capillary column gas-liquid chromatography.
      Using 100 microliters sample volume the lower limit of detection for both
      nicotine and cotinine was 100 pg mL-1, allowing the method to be used for the
      measurement of these compounds in both smokers and non-smokers. The extraction
      time is 3 min per sample, and by using multi-pipetting and vortexing systems 250
      samples can be extracted per day. The average coefficient of variation over the
      nicotine range 1.0 to 100 ng mL-1 was 3.9% and for cotinine over the range 1.0 to
      1000 ng mL-1 was 2.2%. Saliva cotinine concentrations were quantitatively related
      to passive exposure to parental smoking in a population study of 1118 non-smoking
      schoolchildren.

PMID- 1979633
TI  - Systemic vasculitis in the 1980s--is there an increasing incidence of Wegener's
      granulomatosis and microscopic polyarteritis?
AB  - Thirty-six cases of Wegener's granulomatosis (WG) and microscopic polyarteritis
      (MPA) presenting to the nephrology service in Leicester between 1980 and 1989
      were reviewed. Apart from the diagnostic respiratory tract lesions seen in WG,
      cases of MPA and WG could not be distinguished by age and sex, range and severity
      of organ involvement, response to treatment (oral prednisolone and
      cyclophosphamide), mortality or renal outcome. The combined incidence of WG and
      MPA in 1980-86 was 1.5/million/year. Following the introduction in January 1987
      of an assay for anti-neutrophil cytoplasmic antibody (ANCA), the incidence of WG
      and MPA increased in 1987-89 to 6.1/million/year (p less than 0.0001). Cases seen
      during these two periods did not differ by any clinical parameter except that
      later cases had less severe renal disease at referral and improved renal outcome.
      Median serum creatinine was significantly lower at presentation in 1987-89 (p
      less than 0.02). Of those surviving 3 months from presentation only 1/20 in 1987
      89 had end stage renal failure compared with 4/10 in 1980-86 (p less than 0.02).
      These findings may reflect increasing diagnostic awareness of WG and MPA among
      physicians since the introduction of ANCA.

PMID- 1979634
TI  - Investigation of exercise stress by antihypertensive treatment with a combination
      containing beta-blocker/diuretic or reserpine.
AB  - The effects of a beta-blocker/diuretic combination and a reserpine-containing
      combination on exercise hypertension were compared in 20 patients suffering from
      mild hypertension with a diastolic pressure between 90 and 105 mmHg and a
      positive exercise test. This double-blind, randomized, within-patient, cross-over
      study involved two four-week phases, each preceded by a two-week wash-out period.
      The effect on the double product (tension-time index) and the physical working
      capacity at a heart rate of 170 bpm (PWC170) was also measured. The advantage of
      the preparation containing the beta-receptor blocker was apparent in both phases
      as physical work load increased. The PWC170 was twofold greater in the beta
      receptor blocker group than in the reserpine group. The tension-time index was
      lowered in the normal range in both phases by the beta-blocker combination. The
      reserpine-containing preparation in the second phase did not further enhance the
      improvement produced by the beta-blocker in the first phase. These results
      suggest that it is worth questioning the traditional antihypertensive treatment
      in elderly patients, in whom mild hypertension is common, in order to better
      protect them from cardiovascular complications.

PMID- 1979635
TI  - Antihypertensive effect of bopindolol: a multi-centre study.
AB  - The objective of the study was to investigate the efficacy of different dose
      levels of bopindolol monotherapy in hypertension. This potent nonselective beta
      adrenergic receptor blocker has intrinsic sympathomimetic activity and long
      duration of action. Forty-four patients with essential hypertension of mild (n =
      40) or moderate (n = 4) severity (90 less than DBP less than or equal to 115 mmHg
      at the end of the placebo period) entered and completed the single-blind, placebo
      controlled trial. The study lasted 14 weeks: 2 weeks on placebo, and 12 weeks on
      active treatment during which the initial dose of bopindolol, 1 mg daily, was
      augmented up to 1.5 mg, then to 2 mg at four-week intervals until BP normalized
      or a maximum dose of 2 mg/day bopindolol was reached. The bopindolol was
      administered once a day in the morning. Patients were seen every other week in
      the morning before drug taking, when BP and heart rate, supine and standing, a
      twelve lead ECG and side-effects were recorded. Compared with placebo, supine BP
      was significantly reduced by bopindolol: from 169 +/- 2/103 +/- 1 mmHg to 148 +/-
      3/92 +/- 1, 144 +/- 3/90 +/- 1 and 136 +/- 2/85 +/- 0.6 mmHg at the end of 4, 8
      and 12 weeks of treatments, respectively (P less than 0.01 for each). BP changes
      during standing were similar. Bopindolol lowered the supine heart rate from 84 +/
      2 to 75 +/- 1, 74 +/- 1, 72 +/- 1 beats/min (P less than 0.01).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1979636
TI  - Takayasu's arteritis. Carotid duplex sonographic appearance, including color
      Doppler imaging.
AB  - Takayasu's arteritis (also known as pulseless disease, aortoarteritis, and aortic
      arch syndrome) is a chronic inflammatory arteriopathy that affects the aorta and
      its main branches as well as the pulmonary arteries. We report the carotid duplex
      sonographic findings of Takayasu's arteritis in three patients. Takayasu's
      arteritis can be suspected by noting a long segment of diffuse, homogeneous,
      circumferential vessel wall thickening in the proximal common carotid artery,
      resulting in narrowing of the lumen. The internal and external carotid arteries
      are normal.

PMID- 1979637
TI  - Changes in immunoreactive somatostatin and TRH of the brain and CSF in the
      development of cat amygdaloid kindling.

PMID- 1979638
TI  - A GABA and glutamate immunocytochemical study of cortical neurons of temporal
      epilepsy in humans.

PMID- 1979639
TI  - Excitatory amino acid kindling in rats.

PMID- 1979640
TI  - Renovascular effects of angiotensin II. A symposium. Budapest, Hungary, July 16
      19, 1989. Proceedings.

PMID- 1979641
TI  - [Microsurgical methods in pediatric surgery].
AB  - The paper deals with the results of treatment of 32 children aged from 2 to 12
      years with injuries to the arteries (n = 7), tendons of the hand and fingers (n =
      9), nerves of the fingers (n = 3), cryptorchidism (n = 6), tumour of a finger (n
      = 1), and traumatic amputation of a finger (n = 1). Drainage of a lymph vessel in
      the foot for lymph infusion in +suppurative conditions was carried out in 8
      patients. Optic magnification, inert suture material, and microsurgical
      instruments were used in the operations. The anatomical and functional results
      were excellent and good in 30 patients. In an 8-year-old girl, the results of a
      restorative operation on the flexor tendons of the ring finger of the left hand
      were satisfactory. In a boy two and a half years of age, replantation of the
      index finger of the left hand proved a failure. Microsurgical methods make it
      possible to attain utmost precision in forming vascular anastomoses, applying
      sutures to the nerves of the fingers and tendons, and in other operations.
      Microsurgery holds much promise in pediatric surgery.

PMID- 1979642
TI  - [Incarcerated inguinal hernia associated with invagination and torsion of the
      undescended testis in a child].

PMID- 1979644
TI  - Hormonal treatment of cryptorchidism.

PMID- 1979643
TI  - [Alterations of the cAMP-adenylate cyclase system in the failing human heart.
      Consequences for the therapy with inotropic drugs].
AB  - In heart failure, an increase in the activity of the sympathetic nervous system
      takes place to maintain perfusion pressure to vital organs, resulting in
      increased levels of noradrenaline in the blood of these patients. This permanent
      stimulation produces a down-regulation of cardiac beta-adrenoceptors. Since
      noradrenaline acts primarily on the cardiac beta 1-adrenoceptor subtype, beta 1
      adrenoceptors decrease in number, whereas the beta 2-adrenoceptor subpopulation
      remains unchanged in most instances. Consequently, the positive inotropic
      response to beta-adrenoceptor agonists is diminished. However, there is also a
      decrease in the positive inotropic effect of beta 2-adrenoceptor agonists,
      histamine and cAMP-phosphodiesterase inhibitors such as milrinone, whereas the
      positive inotropic effect of cAMP-independent Na(+)-channel activators such as
      DPI 206-106 and the effects of cardiac glycosides are not diminished. These
      observations suggest a more generalised alteration of the cAMP-adenylate cyclase
      system in the failing heart. Stimulatory guanine nucleotide-binding protein (Gs)
      couples receptors to adenylate cyclase that stimulate cAMP formation, such as
      beta-adrenoceptors, histamine receptors and glucagon receptors. In the failing
      human heart, Gs content has been reported to remain unchanged as compared with
      that in non-failing myocardium. However, there is a 35%-40% increase in
      inhibitory guanine nucleotide-binding proteins (Gi), which are involved in the
      receptor-mediated inhibition of adenylate cyclase. Taken together, two defects of
      the cAMP-adenylate cyclase system have been identified: an increase in Gi content
      and a decrease in the number of beta-adrenoceptors.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1979645
TI  - Effects of the antisense v-myb' expression on K562 human leukemia cell
      proliferation and differentiation.
AB  - Recombinant plasmids containing v-myb' (803 bp fragment of the 3' end of v-myb)
      were constructed to induce sense or antisense v-myb' RNA expression with
      dexamethasone in human cells. These plasmids were used as a tool for the
      investigation of the role of c-myb gene in human leukemia cell proliferation and
      differentiation. They were transfected by electroporation into the K562 human
      leukemia cell line derived from a patient with chronic myelogenous leukemia in
      blastic crisis. After induction of transcription by dexamethasone, the plasmid
      with antisense v-myb' repressed the expression of p75c-myb from the endogenous c
      myb gene of K562 cells. It also reduced the proliferation rate of K562 cells to
      50% of the control level, and induced these K562 cells to express the
      myelomonocytic differentiation cell surface marker CD13 and increased NBT
      reducing activity. The plasmid with sense v-myb' did not have an effect on p75c
      myb expression, the proliferation of K562 cells or the expression of
      myelomonocytic differentiation phenotypes. These observations suggest that
      antisense v-myb' RNA represses p75c-myb expression and that a decrease of p75c
      myb suppresses K562 cell proliferation and induces its differentiation towards
      the myelomonocytic lineage.

PMID- 1979646
TI  - Intracerebral microdialysis as a tool to monitor transmitter release from grafted
      cholinergic and monoaminergic neurons.
AB  - In the present study the microdialysis technique has been used as a tool for the
      study of functional regulation of intracerebrally grafted cholinergic and
      monoaminergic neurons as well as for the analysis of graft-host interactions.
      Fetal noradrenergic, serotonergic, dopaminergic, and cholinergic neurons were
      transplanted into the hippocampus or striatum previously denervated of their
      intrinsic monoaminergic or cholinergic afferents. After a few months survival,
      when the grafts had reinnervated the surrounding target, dialysis probes were
      implanted into the graft-reinnervated region. Although the graft-derived fiber
      and terminal density varied substantially from one animal to another the
      transmitters in the extracellular space were maintained at near-normal levels,
      not only under baseline conditions, but also during K(+)-induced depolarization,
      transmitter-selective uptake blockade, and tetrodotoxin. This suggests that the
      grafted neurons possess efficient autoregulatory properties despite their ectopic
      location. The results also show that monoamine release in the graft-reinnervated
      host target is impulse-dependent, and that the neurons are spontaneously
      functionally active at the synaptic level. Electrical stimulation of the lateral
      habenula (which has previously been identified as a powerful activator of the
      intrinsic hippocampal cholinergic and noradrenergic afferents) produced a similar
      increase in the release of these transmitters in the intact and grafted
      hippocampi. A complex environmental stimulus, such as handling, induced a
      consistent increase in acetylcholine but not noradrenaline release in the
      hippocampus. These findings suggest that grafted cholinergic and noradrenergic
      neurons can be functionally activated by host brain inputs.

PMID- 1979647
TI  - Dopamine-acetylcholine interaction in the striatum studied by microdialysis in
      the awake rat: some methodological aspects.
AB  - In order to evaluate the dopamine/acetylcholine balance hypothesis, sulpiride, (
      )-N-0437, oxotremorine or physostigmine were administered intraperitoneally to
      rats, whereas the extracellular levels of acetylcholine and dopamine in the
      striatum were recorded by microdialysis. The changes in dialysate concentration
      of the transmitters did not support the supposed interaction between dopaminergic
      and cholinergic neurons. Next, we infused direct and indirect dopamine agonists
      such as (-)-N-0437, amphetamine and nomifensine via the dialysis membrane. The
      dopamine agonists had no effect on the release of acetylcholine when the calcium
      concentration of the perfusion fluid was 3.4 mmol/l, but the agonists effectively
      inhibited the release of the transmitter when the calcium concentration was 1.2
      mmol/l. The cholinergic drugs physostigmine, oxotremorine, atropine did not
      affect the release of dopamine.

PMID- 1979649
TI  - Measurement of the in vitro release of endogenous monoamine neurotransmitters as
      a means of identification of prejunctional receptors.
AB  - In contrast to in vivo release methods, in vitro release techniques utilising
      brain slices or synaptosomes affords a simple and reproducible means of measuring
      both receptor affinity and efficacy of drugs acting at prejunctional receptors in
      the CNS. Most studies have used brain tissue loaded with radiolabelled
      neurotransmitter or its precursor via the high affinity uptake system for these
      substances which are present on nerve terminals. Depolarisation evoked release
      induced by either high K+ or electrical field stimulation increases the release
      of radioactivity and this overflow can be readily measured by liquid
      scintillation counting. Recent studies have started to emphasise the measurement
      of the release of endogenous neurotransmitters from brain tissue using similar
      depolarisation stimuli. Examples include the release of dopamine, noradrenaline,
      adrenaline and 5-HT and their control by presynaptic receptors. Most of these
      studies have used HPLC with ECD detection as a means of separating and analysing
      for the transmitter of interest. The relative strengths and weaknesses of the
      measurement of radiolabelled or endogenous neurotransmitter release in vitro as a
      means of identifying presynaptic receptors is discussed.

PMID- 1979648
TI  - Effect of food intake on cardiovascular control in patients with impaired
      autonomic function.
AB  - Food intake results in a variety of responses, with the autonomic nervous system
      playing an important role in maintaining cardiovascular homeostasis. In patients
      with autonomic failure, who have severe sympathetic impairment, food
      substantially lowers blood pressure even in the supine position. This is related
      to a marked increase in splanchnic blood flow, without compensatory changes in
      the rest of the circulation. Of the food components, glucose causes similar
      effects to food, while an isosmotic, isocaloric load of the inert carbohydrate,
      xylose, causes only a small fall in blood pressure. Lipid causes a small, short
      lived fall in blood pressure and protein causes minimal change. Insulin appears
      to contribute to the fall in blood pressure, as bolus injections of insulin (even
      before ensuing hypoglycaemia), or insulin infusions (with an euglycaemic clamp),
      when given intravenously lower blood pressure. Other vasodilatatory gut peptides
      released by food may also play a role. The somatostatin analogue, Octreotide (SMS
      201-995), which inhibits the release of a range of peptides, prevents both
      glucose and food-induced hypotension. Studies of the mechanisms responsible for
      post-prandial hypotension in autonomic failure continue to provide insight into
      the relationship between food intake and the hormonal, peptidergic and neural
      responses which affect the cardiovascular system.

PMID- 1979650
TI  - Brain dialysis of neurotransmitters: a commentary.
AB  - Brain dialysis has become an important tool for investigating changes in the
      extracellular levels of neurotransmitters. This paper reviews the experimental
      variables and criteria that should be considered when interpreting data obtained
      with the brain dialysis method. Brain dialysis can provide important direct
      information on the effect of drugs on transmitter release as shown using
      dopaminergic agonists and antagonists, monoamine uptake inhibitors and drugs of
      abuse.

PMID- 1979651
TI  - In vivo voltammetry with micro-biosensors for analysis of neurotransmitter
      release and metabolism.
AB  - In vivo voltammetry involves the electrochemical detection of central oxidisable
      substances in situ. In association with this technique micro carbon fibre
      electrodes (CFE) are able to separate ascorbic acid (Peak 1) from 3,4
      dihydroxyphenylacetic acid (DOPAC) plus dopamine (DA) (Peak 2) and 5
      hydroxyindoleacetic acid (5-HIAAA) plus serotonin (5-HT) (Peak 3) in vitro. In
      vivo these biosensors detect the amine metabolites, due to their high
      extracellular concentration (microM) compared to the amines (nM). In addition
      homovanillic acid (HVA) (or 3-methoxytyramine (3-MT) in pargyline-pretreated
      mice) (Peak 4) and somatostatin (Peak 5) were also measured in vivo. However,
      potassium-stimulated release of DA has been directly monitored in pargyline
      pretreated mice. In addition, low concentrations (nM) of DA and 5-HT can now be
      selectively monitored in vitro with new biosensors coated with Nafion which
      repels negatively charged species including acid metabolites. In vivo, the
      combination of the Nafion-CFE and normal CFE allowed simultaneous measurements of
      release and metabolism of 5-HT, respectively. This permitted the observation that
      changes in 5-HT release are not necessarily reflected by changes in 5-HIAA
      levels. At present we are developing a Nafion biosensor to monitor basal
      extracellular DA. Electron microscope studies have shown radical modifications in
      the surface and structure of carbon fibres following chemical and electrical
      pretreatments, which may be involved in the development of sensitivity and
      selectivity displayed by the pretreated CFE towards electroactive compounds. A
      new approach for selective detection of neuroamines is the analysis of their
      stimulated fluorescence using LASER. In vitro, the fluorescence of 5-HT is in
      fact clearly distinguishable from that of 5-HIAA. The feasibility of this
      methodology in vivo using fiber optic probes will be explored.

PMID- 1979652
TI  - Fast cyclic voltammetry: measuring transmitter release in 'real time'.
AB  - Fast cyclic voltammetry (FCV) differs from all other voltammetric methods in the
      type of waveform used, the speed of measurement and the applications for which it
      is best suited. The main assets of FCV are its high spatial and temporal
      resolution, the use of a reduction scan and the ease with which it can be
      combined with unit activity recording at the same electrode. The drawbacks of the
      method are the inability to measure basal extracellular amine levels or changes
      in multicomponent signals, and the modest sensitivity of the technique. Principal
      applications of FCV are the monitoring of ionophoresed or pressure-ejected
      monoamines, direct measurement of stimulated amine release and uptake, and the
      study of brain ascorbic acid function. The high spatial (5 microns) resolution of
      FCV is such that the anatomical heterogeneity of brain nuclei can be measured in
      great detail. The temporal resolution (25 ms) means that transmitter release and
      uptake can be measured essentially in 'real time'.

PMID- 1979653
TI  - Modulation of NMDA receptor responsiveness by neurotransmitters, drugs and
      chemical modification.
AB  - The NMDA receptor is intimately involved an a wide range of pathophysiological
      processes in the mammalian brain, including epilepsy and ischemia-induced
      neurodegeneration. The widespread distribution of NMDA receptors places almost
      every area of the brain at risk from NMDA receptor over-activity. However, it is
      clear that the central nervous system can function effectively without imminent
      danger of self-destruction. The focus of this review is the processes that
      control NMDA receptor responsiveness in vivo. The review will cover the
      modulation of the receptor by Mg2+, glycine, Zn2+ and polyamines that is believed
      to occur by virtue of interaction with distinct ligand binding sites on the NMDA
      receptor complex. Studies suggesting a role for receptor phosphorylation and for
      redox modulation will be discussed. Finally, some evidence for indirect
      regulation of cellular responses to NMDA receptor activation by other
      neurotransmitters will be presented.

PMID- 1979654
TI  - Is immune oversuppression the direct cause of AIDS?
AB  - AIDS is presumably caused by HIV, a retrovirus. The main support for this view
      comes from the consistent epidemiological correlation between AIDS and the
      presence of antibody against HIV. Several HIV-associated mechanisms have been
      described to explain the cytopathic effects on helper-T-lymphocytes observed in
      vitro but so far, none of these mechanisms has been confirmed in vivo. On the
      other hand, there is virtually no free virus and HIV RNA synthesis is very low
      both in AIDS patients and in asymptomatic carriers. Thus it is unlikely that HIV
      causes AIDS by acting as a conventional cytocidal virus. Here it is proposed, on
      the basis of current experimental evidence, that an active immune suppression
      mediated by T8+ cells is the direct culprit for a gradual decline of helper-T
      lymphocyte numbers leading to an immunocompromised state in AIDS. The role of HIV
      in triggering and perpetuating a state of immune oversuppression is discussed.

PMID- 1979655
TI  - The concept of migraine as a state of central neuronal hyperexcitability.
AB  - This article explores the hypothesis that migraine with aura is associated with a
      state of central neuronal hyperexcitability. The authors propose that this
      central neuronal hyperexcitability involves overactivity of the excitatory amino
      acids, glutamate, and possibly aspartate. Stimuli that activate the migraine
      attack evoke neuronal depolarization, slow depolarization shifts, and spreading
      suppression of spontaneous neuronal activity possible by glutamate and K+
      dependent mechanisms. A low brain Mg2+ and consequent reduced gating of
      glutamatergic receptors may provide the link between the physiologic threshold
      for a migraine attack and the mechanisms of the attack itself by promoting
      glutamate hyperactivity, neuronal hyperexcitability, and susceptibility to
      glutamate-dependent spreading depression.

PMID- 1979656
TI  - Mitochondrial DNA analysis in Parkinson's disease.
AB  - The reduced form of nicotinamide adenine dinucleotide coenzyme Q reductase
      (complex I) activity has recently been shown to be deficient in the substantia
      nigra of patients dying with Parkinson's disease. This biochemical defect is
      identical to that produced by the neurotoxin 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP), which also produces parkinsonism in humans. Complex I
      comprises 25 polypeptides, seven of which are encoded by mitochondrial DNA.
      Restriction fragment analysis of substantia nigra DNA from six patients with
      Parkinson's disease did not show any major deletion. In two cases, there were
      different novel polymorphisms that were not observed in control brain (n = 6) or
      blood (n = 34) samples.

PMID- 1979657
TI  - Sustained-release (+)-PHNO [MK-458 (HPMC)] in the treatment of Parkinson's
      disease: evidence for tolerance to a selective D2-receptor agonist administered
      as a long-acting formulation.
AB  - 4-Propyl-9-hydroxynaphthoxazine, or MK-458 (HPMC), a selective, nonergot D2
      agonist administered orally twice a day in sustained-release form, was studied as
      adjunctive therapy with carbidopa-levodopa (Sinemet) in 12 Parkinson's disease
      patients with motor response fluctuations. The dosage of agonist was gradually
      increased over 12 weeks to a maximum tolerated level of up to 60 mg/day, and that
      of Sinemet was reduced concurrently. After 8 weeks, reduction of Sinemet averaged
      45.1%, but over the next 4 weeks, despite a continued increase in dosage of the
      agonist, patients were unable to decrease their Sinemet further, and by 12 weeks
      mean reduction in Sinemet was only 32%. Only five patients completed the planned
      24-week study, mostly due to progressive loss of efficacy. The MK-458 is capable
      of partially substituting for Sinemet in dosages employed in this study. Reduced
      sensitivity to the drug can appear over a relatively short time, perhaps as a
      result of down-regulation of postsynaptic dopamine receptors.

PMID- 1979658
TI  - Prevalence of dystonia in veterans on chronic antipsychotic therapy.
AB  - The prevalence of dystonia was studied in 125 veterans on chronic antipsychotic
      therapy using a detailed and systematic examination. Twenty-seven out of 125 had
      dystonic manifestations. The most common areas involved were hands and jaw. There
      was no relation between the presence or absence of dystonia, and duration of
      neuroleptic therapy. There was a tendency for tardive akathisia to occur more
      frequently in patients with dystonia than in those without it (Fisher's exact
      probability test, p = 0.0656). Tardive dystonia in its milder forms may be more
      common than currently believed.

PMID- 1979659
TI  - The let-23 gene necessary for Caenorhabditis elegans vulval induction encodes a
      tyrosine kinase of the EGF receptor subfamily.
AB  - The let-23 gene is required for induction of the Caenorhabditis elegans vulva. It
      is shown that let-23 encodes a putative tyrosine kinase of the epidermal growth
      factor receptor subfamily. Thus, let-23 might encode the receptor for the
      inductive signal required for vulval development. Because let-23 acts upstream of
      let-60 ras in the vulval determination pathway, the identification of the let-23
      product provides support for a link in vivo between tyrosine kinase growth factor
      receptors and ras proteins in a pathway of cell-type determination.

PMID- 1979661
TI  - Ventricular fluid neuropeptides in Parkinson's disease. I. Levels and
      distribution of somatostatin-like immunoreactivity.
AB  - We have measured somatostatin-like immunoreactivity SLI in cerebroventricular
      fluid of patients with Parkinson's disease (PD) and other extrapyramidal
      disorders with hyperkinesia. Patients with PD showed a significantly lower
      concentration of SLI when compared with levels in control patients with chronic
      stable multiple sclerosis or temporal lobe epilepsy. Less markedly decreased
      levels of SLI were also noted in patients with torsion dystonia. Of two patients
      with Huntington's disease one showed a high and one a medium concentration of
      SLI. According to the site of the stereotactic cannula, verified by
      ventriculopathy, SLI concentrations in CSF specimen obtained from the foramen
      Monro tended to be higher than in specimen from a supraforaminal level. Of 5
      other patients with lateral and third ventricle being accessible during the
      passage of the stereotactic cannula, 4 showed higher SLI concentrations in the
      third ventricle compared to the lateral ventricle. High performance liquid
      chromatographic analysis combined with radioimmunoassay showed molecular
      heterogeneity of SLI in CSF. The ratio of SST-14 to SST-28 was higher in the
      third ventricle than in the lateral ventricle.

PMID- 1979660
TI  - MHC class II region encoding proteins related to the multidrug resistance family
      of transmembrane transporters.
AB  - The T-cell immune response is directed against antigenic peptide fragments
      generated in intracellular compartments, the cytosol or the endocytic system.
      Peptides derived from cytosolic proteins, usually of biosynthetic origin, are
      presented efficiently to T-cell receptors by major histocompatibility complex
      (MHC) class I molecules, with which they assemble, probably in the endoplasmic
      reticulum (ER). In the absence of recognizable N-terminal signal sequences, such
      cytosolic peptides must be translocated across the ER membrane by a novel
      mechanism. Genes apparently involved in the normal assembly and transport of
      class I molecules may themselves be encoded in the MHC. Here we show that one of
      these, the rat cim gene, maps to a highly polymorphic part of the MHC class II
      region encoding two novel members of the family of transmembrane transporters
      related to multidrug resistance. Other members of this family of transporter
      proteins are known to be capable of transporting proteins and peptides across
      membranes independently of the classical secretory pathway. Such molecules are
      credible candidates for peptide pumps that move fragments of antigenic proteins
      from the cytosol into the ER.

PMID- 1979662
TI  - Somatostatin inhibition of VIP- and isoproterenol-stimulated cyclic AMP
      accumulation in dissociated cells from rat cerebral cortex.
AB  - Freshly dissociated cerebral cortex cells from adult rats have been used in the
      present study to determine if dual regulation of cyclic AMP levels by inhibitory
      and stimulatory agents can be expressed in the mature brain. Somatostatin, an
      inhibitory agent, barely affected the basal cyclic AMP metabolism while
      vasoactive intestinal peptide (VIP) and isoproterenol, two stimulatory agents
      enhanced cyclic AMP production. However, this increase was depressed by
      somatostatin, which decreased the efficiency, but not the potency, of the effects
      of the two stimulatory agents on cyclic AMP accumulation.

PMID- 1979664
TI  - Autoradiographic distribution of binding sites for the non-NMDA receptor
      antagonist CNQX in chick brain.
AB  - The anatomical distribution of binding sites for the non-N-methyl-D-aspartate
      (non-NMDA) glutamate receptor antagonist [3H]6-cyano-7-nitroquinoxaline-2,3-dione
      ([3H]CNQX) in 1-day-old chick brain was investigated. Specific [3H]CNQX binding
      sites were widely distributed but were particularly densely localised in the
      molecular layer of the cerebellum. In the midbrain, the binding was comparatively
      low, except for relatively high levels in the nucleus isthmi of the optic lobe.
      The distribution of [3H]CNQX binding was markedly different to that of the NMDA
      receptor ligand [3H]MK-801. Overall, the localisation of [3H]CNQX binding was
      similar to the combined distributions of [3H]AMPA and [3H]kainate binding sites.
      Kainate inhibited [3H]CNQX binding throughout the brain. AMPA also inhibited
      [3H]CNQX binding in the fore- and midbrain, but the dense binding in the
      molecular layer of the cerebellum was notable in being AMPA-insensitive.

PMID- 1979663
TI  - A 3,4-dihydroxyphenylalanine oxidation product is a non-N-methyl-D-aspartate
      glutamatergic agonist in rat cortical neurons.
AB  - Applications of solutions of 2,4,5-trihydroxyphenylalanine (TOPA or 6
      hydroxyDOPA) to rat cortical neurons in culture monitored under whole-cell
      voltage clamp with patch electrodes resulted in currents which could be nearly
      completely blocked by the non-N-methyl-D-aspartate (non-NMDA) antagonist 6-cyano
      7-nitroquinoxaline-2,3-dione (CNQX), but only weakly antagonized by the NMDA
      antagonist D.L-2-amino-5-phosphonovalerate (APV). Thus, TOPA can generate
      glutamatergic responses by interacting preferentially with non-NMDA receptors in
      cortical neurons. As these results show that a product closely related to the
      catecholamine precursor 3,4-dihydroxyphenylalanine (DOPA) has glutamatergic
      agonist properties, it is conceivable that catecholamine-containing brain areas
      may be at special risk for excitotoxic damage under certain conditions.

PMID- 1979665
TI  - Quisqualate-induced changes in extracellular sodium and calcium concentrations
      persist in the combined presence of NMDA and non-NMDA receptor antagonists in rat
      hippocampal slices.
AB  - In the CA1 stratum pyramidale of rat hippocampal slices we have used Ca2(+)- and
      Na(+)-sensitive microelectrodes to measure the changes in [Ca2+]o, [Na+]o and
      associated slow field potentials elicited by the iontophoretic application of the
      excitatory amino acids N-methyl-D-aspartic acid (NMDA), quisqualic acid (Quis),
      alpha-amino-3-hydroxy-5-methyl-4-isoazolepropionic acid (AMPA) and glutamic acid
      (Glu) in the presence of the NMDA receptor antagonists 2-amino-5-phosphonovaleric
      acid (AP5) and ketamine and the non-NMDA receptor antagonist 6-cyano-7
      nitroquinoxaline-2,3-dione (CNQX). Although a combination of these antagonists
      blocked stimulation-induced synaptic field potentials as well as AMPA- and NMDA
      induced ionic changes and associated field potentials, Quis-induced ionic changes
      and associated field potentials could still be observed after 60 min. These
      residual Quis signals were also resistant to 2-amino-3-phosphonopropionic acid
      (AP3) and 2-amino-4-phosphonobutyric acid (AP4) suggesting that metabotropic
      receptors do not play a role in the generation of these signals. We suggest that
      the receptor class activated under these conditions may play a role in CNQX/AP5
      resistant epileptogenesis as well as other pathophysiological conditions.

PMID- 1979666
TI  - Ifenprodil and SL 82.0715 potently inhibit binding of [3H](+)-3-PPP to sigma
      binding sites in rat brain.
AB  - SL 82.0715 and ifenprodil are potent anti-ischemic agents, which are believed to
      be due to non-competitive antagonism of N-methyl-D-aspartate (NMDA). It has been
      proposed that SL 82.0715 and ifenprodil non-competitively antagonize the actions
      of NMDA by interacting as antagonists with a polyamine site associated with the
      NMDA/phencyclidine (PCP)/glycine complex. The present study demonstrates that the
      actions of SL 82.0715 and ifenprodil may also be due in part to an interaction
      with sigma binding sites, a property that is not shared with polyamines.

PMID- 1979667
TI  - Immunolocalization of tyrosine hydroxylase and vasoactive intestinal polypeptide
      in nerve fibers innervating human palatine tonsil and paratonsillar glands.
AB  - The presence of tyrosine hydroxylase (TH) and vasoactive intestinal polypeptide
      (VIP) in the nerve fibers of the human palatine tonsil and paratonsillar
      secretory glands is reported. By immunohistochemistry TH-immunoreactive nerves
      and those immunoreactive to VIP were localized to the tonsil, in particular, the
      tonsillar vessel wall, extranodular lymphoid tissue and lymph nodule, and to the
      acinar basal surface of the paratonsillar glands. In the lymph nodule,
      immunoreactive varicose nerve profiles were observed inside the marginal zone.
      The germinal center was devoid of immunoreactive fibers.

PMID- 1979668
TI  - Tyrosine hydroxylase-like (TH) immunoreactivity in human mesolimbic system.
AB  - A practical methodology has been described for the use of human postmortem brain
      tissue in both tyrosine hydroxylase and dopamine beta-hydroxylase
      immunohistochemistry in which in situ perfusion with paraformaldehyde is followed
      by immersion fixation in Bouin's fixative. These studies indicate that TH-like
      immunoreactive fibers and terminals are not uniformly distributed in the human
      hippocampal complex. A distinctive lesser innervation is noted for the structures
      that compose the perforant pathway and may be important for the predilection of
      these areas for pathological change particularly as occurs in Alzheimer's
      disease.

PMID- 1979669
TI  - Depolarizing pulses to neuromuscular terminals of frogs can elicit graded, phasic
      transmitter release in the absence of Ca influx.
AB  - Quantal synaptic currents were recorded by means of a macro-patch-clamp
      electrode, through which the terminal could be also depolarized by current
      pulses. The tip of the electrode was perfused rapidly, applying either Ringer's
      solution or an EGTA-buffered less than 0.1 microM Ca Ringer's. Muscle and nerve
      outside the electrode were superfused with normal or 10 mM Ca Ringer which served
      to keep the resting intracellular Ca concentration, Cair, in the terminal below
      the electrode relatively high. When Ca inflow was prevented by decreasing the Ca
      concentration to less than 0.1 microM, release was depressed, but still
      measurable, for low depolarizations, and much less or not at all depressed for
      large depolarizations to positive membrane potentials. The time course of the
      depressed release without Ca-inflow was the same as that in the controls with Ca
      inflow. It appears that the voltage dependent activator proposed in the Ca
      voltage theory of release can elicit maximal release in the absence of Ca inflow,
      provided Cair is sufficiently high. The voltage dependencies of this activator as
      well as that of Ca inflow can be estimated from the results.

PMID- 1979671
TI  - The A11 catecholamine cell group: another origin of the dopaminergic innervation
      of the amygdala.
AB  - A combination of fluorescent retrograde tracing and immunofluorescence
      histochemistry for tyrosine hydroxylase was employed to re-examine the origin of
      the dopaminergic innervation of the amygdala in the rat. The present data show
      that the major input source of this innervation includes the subparafascicular
      thalamic nucleus as well as the substantia nigra pars compacta and ventral
      tegmental area, but not the substantia nigra pars lateralis.

PMID- 1979670
TI  - Interaction of cholinergic and glutamatergic transmission in the hippocampus: an
      in vitro autoradiographic receptor analysis.
AB  - Quantitative in vitro receptor autoradiography was used to examine the effect of
      acute scopolamine administration on specific binding to components of the N
      methyl-D-aspartate (NMDA) receptor complex in four regions of mouse hippocampus.
      The binding of [3H]glycine to the strychnine-insensitive site was increased 1 h
      after administration of scopolamine hydrobromide (10 mg/kg) in the ventral
      dentate gyrus. The study suggests that rapid alterations in strychnine
      insensitive glycine binding can occur in response to cholinergic perturbations.
      Moreover, these data suggest a delicate interaction between cholinergic and
      glutamatergic projections in the hippocampus.

PMID- 1979672
TI  - Increased somatostatin and enkephalin-like immunoreactivity in the rat
      hippocampus following hippocampal kindling.
AB  - As neuropeptides may play a role in the electrical kindling model of
      epileptogenesis, hippocampal somatostatin, Met-enkephalin and cholecystokinin
      were studied by immunocytochemistry in rats 24 h following full hippocampal
      kindling (three stage 5 seizures). As control animals we used sham-kindled rats,
      unoperated rats and rats subjected to a single electroshock-induced seizure. In
      addition, the distribution of septohippocampal, cholinergic fibers and
      hippocampal mossy fibers were studied by histochemistry. The important finding
      was that after kindling there was, as compared to unoperated control, (1) a
      marked increase of somatostatin immunoreactivity in cell bodies in the dentate
      hilus and their presumed projections area in the outer parts of the dentate
      molecular layer, and (2) a marked increase of Met-enkephalin immunoreactivity in
      hippocampal mossy fiber terminals. We found no evidence of aberrant sprouting of
      mossy fiber collaterals in the fascia dentata.

PMID- 1979674
TI  - Mechanisms of Neural Development and Reorganization. Proceedings of the 15th
      Seiriken Conference on the Molecular and Cellular Mechanisms of Neural
      Development and Reorganization. Okazaki, Japan, February 7-10, 1990.

PMID- 1979673
TI  - A2B5 surface ganglioside binding distinguishes between two GFAP-positive clones
      from a human glioma-derived cell line.
AB  - A human glioma-derived cell line which expresses both the astrocytic markers,
      glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS) and cell
      surface gangliosides recognised by the A2B5 monoclonal antibody has been cloned.
      Two clones are described, which are A2B5-positive and A2B5-negative,
      respectively. These neoplastic clones may provide a suitable in vitro model with
      which to assess the significance of surface ganglioside expression in relation to
      function and lineage of mammalian glia.

PMID- 1979675
TI  - GAP-43 as a 'calmodulin sponge' and some implications for calcium signalling in
      axon terminals.
AB  - In most neurons, the maturation of axonal growth cones to become stable synaptic
      terminals is accompanied by a dramatic decline in the abundance of a major growth
      cone component, GAP-43. Accumulation of GAP-43 persists, however, in a minority
      of mature synaptic terminals. What properties of axons and their terminals are
      affected by these changes in GAP-43 expression? Storm and colleagues first noted
      that the membrane- and calmodulin-binding properties of GAP-43 (a.k.a. P-57 or
      neuromodulin) could allow it to sequester a large fraction of calmodulin to the
      submembranous regions, and to release free calmodulin in response to protein
      kinase C activation. Analysis of evolutionarily conserved sequences in GAP-43
      indicates that these properties are central to the biological effects of the
      protein. If GAP-43 is presumed to inactivate bound calmodulin, the network of GAP
      43 in an axon terminal could be considered a regulatable calmodulin buffer, or
      'calmodulin sponge', absorbing free calmodulin and releasing it in response to
      activation of protein kinase C. Such a calmodulin sponge has properties that
      could be useful in modulating the responses of membrane and cytoskeletal assembly
      events to calcium signals in growth cones, and in mediating long-term
      potentiation of neurotransmitter release from some pre-synaptic terminals.

PMID- 1979676
TI  - Seizure-like activity and glutamate receptors in hippocampal neurons in culture.
AB  - Hippocampal neurons that were grown for prolonged periods in the continuous
      presence of agents that interfere with synaptic transmission, especially
      excitatory synaptic transmission, appeared to become seizure-prone. Washout of
      the synaptic blocking agents, that had been continuously present for several
      weeks to several months, caused the population of neurons to produce an abnormal
      and intense electrical activity. This consisted of two major components:
      spontaneously arising phasic responses that closely resembled paroxysmal
      depolarization shifts and, less frequently, slowly rising depolarizations similar
      to the sustained depolarizations observed during ictus-like episodes in intact
      cortex or cortical slices. We describe here observations on the role of the N
      methyl-D-aspartate (NMDA) and non-NMDA types of glutamate receptors in the
      generation of these activities.

PMID- 1979678
TI  - BamHI RFLP of the inhibin beta B (INHBB) chain gene on chromosome 2.

PMID- 1979677
TI  - The octamer binding factor Oct6: cDNA cloning and expression in early embryonic
      cells.
AB  - We have cloned a cDNA encoding a novel octamer binding factor Oct6 that is
      expressed in undifferentiated ES cells. Expression of the Oct6 gene is
      downregulated upon differentiation of these cells by aggregate formation.
      Furthermore the gene is transiently up regulated during retinoic acid induced
      differentiation of P19 EC cells, reaching maximum levels of expression one day
      after RA addition. Sequence analysis of the cDNA encoding the Oct6 protein
      indicated that the Oct6 gene is a member of the POU-HOMEO domain gene family. The
      gene expresses a 3 kb mRNA encoding a 449 amino acid protein with an apparent
      molecular weight of 45 kD. The sequence of the Oct6 POU domain is identical to
      that of the rat SCIP (Tst-1) gene. The Oct6 expression pattern suggests a role
      for this DNA binding protein in neurogenesis as well as early embryogenesis.

PMID- 1979680
TI  - A PstI polymorphism in the human coagulation factor V (F5) gene.

PMID- 1979679
TI  - PCR assay for a polymorphic PvuII site in the LPL gene.

PMID- 1979681
TI  - Three RFLPs at the 3' end of the cystatin C gene, the disease gene in hereditary
      cystatin C amyloid angiopathy (HCCAA) in Iceland.

PMID- 1979682
TI  - A TaqI RFLP in the human ret proto-oncogene.

PMID- 1979683
TI  - [Lupus-like circulating anticoagulant in periarteritis nodosa].

PMID- 1979684
TI  - Smooth pursuit eye movements in schizophrenia: influences of neuroleptic
      treatment and the question of specificity.
AB  - The authors investigated smooth pursuit eye movements (SPEMs) in 66 schizophrenic
      and 40 major affective patients and 39 healthy controls. The results showed
      significant differences of both patient groups as compared to the controls.
      Schizophrenics with neuroleptic treatment in the preceding 2 years were
      significantly more disturbed than the controls, the affective patients and the
      untreated schizophrenics. Acute neuroleptic medication and neuroleptic treatment
      of a duration of 4-6 weeks appear not to significantly influence the quality of
      SPEMs.

PMID- 1979686
TI  - The pathogenetic role of HLA-B27. Proceedings of the Fifth Bertine Koperberg
      Conference. May 21-23, 1990, Oosterbeek, The Netherlands.

PMID- 1979685
TI  - Vagally induced release of gastrin, somatostatin and bombesin-like
      immunoreactivity from perfused rat stomach. Effect of stimulation frequency and
      cholinergic mechanisms.
AB  - The isolated stomach of rats was vascularly perfused to measure the secretion of
      gastrin, somatostatin (SLI) and bombesin-like immunoreactivity (BLI). The gastric
      lumen was perfused with saline pH 7 or pH 2, and electrical vagal stimulation was
      performed with 1 ms, 10 V and 2, 5 or 10 Hz, respectively. Atropine was added in
      concentrations of 10(-9) or 10(-7) M to evaluate the role of cholinergic
      mechanisms. In control experiments, vagal stimulation during luminal pH 2
      elicited a significant increase of BLI secretion only at 10 Hz but not at 2 and 5
      Hz. Somatostatin release was inhibited independent of the stimulation frequency
      employed. Gastrin secretion at 2 Hz was twice the secretion rates observed at 5
      and 10 Hz, respectively. At luminal pH 7 BLI rose significantly at 5 and 10 Hz.
      SLI secretion was decreased by all frequencies. Gastrin secretion at 2 and 5 Hz
      was twice as high as during stimulation with 10 Hz. Atropine at doses of 10(-9),
      10(-8), 10(-7) and 10(-6) M had no effect on basal secretion of BLI, SLI and
      gastrin. At luminal pH 2, atropine increased dose-dependently the BLI response at
      2 and 5 but not at 10 Hz. The decrease of SLI during 2 and 5 Hz but not 10 Hz was
      abolished by atropine 10(-9) M. SLI was reversed to stimulation during atropine
      10(-7) M at all frequencies. The rise of gastrin at 2 Hz was reduced by 50%. At
      luminal pH 7, atropine had comparable effects with a few differences: the BLI
      response at 10 Hz was augmented and the gastrin response to 2 and 5 Hz was
      reduced. In conclusion the present data demonstrate a frequency and pH-dependent
      stimulation of BLI and gastrin release. The stimulation of BLI is predominantly
      due to atropine-insensitive mechanisms while muscarinic cholinergic mechanisms
      exert an inhibitory effect on BLI release during lower stimulation frequencies (2
      and 5 Hz) independent of the intragastric pH and also during higher frequencies
      at neutral pH. Both, atropine sensitive and insensitive mechanisms are activated
      frequency dependent. The atropine-sensitive cholinergic mechanisms but not the
      noncholinergic mechanisms involved in regulation of G-cell function are pH and
      frequency dependent. Somatostatin is regulated largely independent of stimulation
      frequency and pH by at least two pathways involving cholinergic mechanisms of
      different sensitivity to atropine. These data suggest a highly differentiated
      regulation of BLI, gastrin and SLI secretion and the interaction between these
      systems awaits further elucidation.

PMID- 1979687
TI  - Sensitivity of a Dutch Health Assessment Questionnaire in a trial comparing
      hydroxychloroquine vs. sulphasalazine.
AB  - To measure health status in Dutch rheumatoid arthritis patients, we have
      translated and revised the Health Assessment Questionnaire (HAQ) and added
      questions about psychosocial status from the Arthritis Impact Measurement Scales
      (AIMS). The resultant questionnaire turned out to be reproducible and valid. In a
      double-blind trial comparing Hydroxychloroquine and Sulphasalazine, after 48
      weeks the Physical Disability score showed a significant difference in favour of
      the Sulphasalazine group, reflecting the smaller deterioration in radiographic
      damage in this group. Thus the Physical Disability part of the questionnaire is
      sensitive to difference between two slow-acting anti-rheumatic drugs.

PMID- 1979689
TI  - Clinical evaluation of mitoxantrone in lymphoma therapy. June 6, 1990,
      Lugano,Switzerland. Proceedings.

PMID- 1979688
TI  - Bladder neuropathy and gastric paralysis in polyarteritis nodosa associated with
      hepatitis B virus.

PMID- 1979690
TI  - Hormonal therapy in responsive tumors and in the management of human
      immunodeficiency virus and cancer-associated anorexia/cachexia. Proceedings of an
      international conference. April 6-7, Key Biscayne, Florida.

PMID- 1979691
TI  - Stevens-Johnson syndrome in neuroleptic-carbamazepine combination.
AB  - Three cases of Stevens-Johnson Syndrome developing after the addition of
      Carbamazepine to existing neuroleptic medication are described. In all 3, the
      syndrome developed within two weeks of starting Carbamazepine. It is suggested
      that neuroleptic-Carbamazepine combination predisposes the patient to increased
      risk of Stevens-Johnson Syndrome. This observation is pertinent in everyday
      psychiatric practice as there is indication of increasing prescription of
      Carbamazepine.

PMID- 1979693
TI  - [The therapy of acute radiogenic epitheliolysis with a dressing of hydrocolloids
      and polymers (Biofilm). A report on clinical experience].
AB  - Acute skin lesions following radiotherapy are uncomfortable and unacceptable side
      effects. They are observed predominantly after high surface doses as in
      conventional roentgen or electron beam therapy. To accelerate the wound healing
      we tested a bandage consisting of hydrocolloids and polymers, which is permeable
      for gas and water. Handling, compatibility and effectiveness of this plaster were
      tested in this study. According to the RTOG scoring system 19 irradiated fields
      with grade II to IV lesions were treated. Densitometric measurements of
      verification films with and without Biofilm showed no energy absorption. The
      bandage was comfortable for the patients and easy to handle.

PMID- 1979692
TI  - Excitotoxins can produce protein degradation in the spinal cord.
AB  - Overdistraction and derotation of the scoliotic spine during surgery represent
      potential complications that could lead to spinal cord dysfunction and paralysis.
      Neuronal loss and, consequently, the inability to regain function may be
      attributable to primary damage (eg, mechanical), secondary cell death (eg, such
      as that produced by ischemia) or a combination of both. Beyond intraoperative
      recognition and removal of the rods, effective strategies to prevent this
      neuronal loss have yet to be developed. This emphasizes the need for a clearer
      understanding of the molecular events that contribute to neuronal injury in the
      central nervous system. Considerable evidence has indicated that the excitatory
      transmitter L-glutamate and the N-methyl-D-aspartate (NMDA) excitatory amino acid
      receptor may contribute to the secondary neuronal death observed in a wide
      variety of neurological insults, including ischemia. The current investigation
      was undertaken to elucidate the potential role of the NMDA receptor in spinal
      cord pathology. Isolated rat spinal cords were exposed to anoxic physiologic
      solutions in the presence and absence of Ca++, NMDA receptor agonists, and a
      noncompetitive NMDA receptor antagonist. The extent of neuronal damage was
      assessed by quantitating the degradation of the cytoskeletal neurofilament
      protein. A substantial increase in the loss of neurofilament protein was observed
      in spinal cords exposed to anoxic conditions in the presence of Ca++ as compared
      with the absence of Ca++. Exposure to excitatory amino acid agonists (L-glutamate
      or NMDA) further potentiated the degradation of the neurofilament protein; an
      effect that was reversed by a noncompetitive NMDA receptor antagonist.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1979694
TI  - [Combination of slow-release diltiazem and a beta-blocker in arterial
      hypertension. 2 cases of cardiogenic shock with severe bradycardia].
AB  - Patient 1 received carteolol and captopril for hypertension. Three days after a
      slow-release diltiazem preparation (300 mg) had been introduced, he developed
      cardiogenic shock and sinus bradycardia (heart rate: 30/mn) with acidosis and
      severe hyperkaliemia. He was successfully treated by temporary pacing and
      dobutamine. Patient 2 had received sotalol and captopril for several years.
      Twelve hours after slow release diltiazem had been added, he was found in
      cardiogenic shock and extreme bradycardia with wide QRS, acidosis and
      hyperkaliemia. He died one hour later despite intensive emergency treatment.
      Concomitant use of beta-blockers and calcium channel blockers has been reported
      in patients suffering of severe coronary heart disease. However, several adverse
      reactions similar to our cases have been described. Slow-release diltiazem should
      be avoided in hypertensive patients taking beta-blockers.

PMID- 1979695
TI  - Changes in hepatic lipid metabolism associated with lipid accumulation and its
      reversal in rats given the peroxisome proliferator LY171883.
AB  - Dietary administration of 0.05, 0.1, and 0.3% LY171883 to rats for 1 day caused a
      dose-related increase in hepatic triglycerides. When added to rat liver
      mitochondria in vitro, LY171883 caused competitive inhibition of carnitine
      palmitoyltransferase 1 (CPT-1), the rate-limiting enzyme for mitochondrial fatty
      acid oxidation. This effect appears to be involved in the lipid accumulation. The
      hepatic triglycerides in rats given 0.1% LY171883 increased progressively through
      3 months of treatment. In contrast, hepatic triglycerides in high-dose rats
      returned to control levels by Day 3 and remained there throughout the study. The
      regression of the lipid corresponded with increases in hepatic peroxisomal beta
      oxidation, mitochondrial beta-oxidation, and CPT-1 activity of up to 13-, 7-, and
      3.2-fold, respectively. The 0.1% dose increased these parameters modestly
      compared to those of high-dose rats (2-, 3-, and 1.6-fold, respectively).
      Addition of LY171883 to mitochondria from rats given dietary treatment for 2
      weeks inhibited CPT-I by the same percentage as in control mitochondria. In mid
      dose rats, the induction of CPT-I was largely negated by LY171883 in vitro. Even
      with the inhibition, CPT-I activity in mitochondria from high-dose rats remained
      2-fold higher than that in untreated controls. The data suggest that the
      induction of CPT-I in high-dose rats was sufficient to overcome the inhibitory
      action of LY171883. The increased oxidative capacity in peroxisomes and
      mitochondria led to the regression of the lipid in high-dose rats. The more
      modest increases in fatty acid oxidation in rats given 0.1% LY171883 were not
      sufficient to reverse the lipid accumulation.

PMID- 1979696
TI  - Increase of mammalian intestinal motility by the iminopurine caissarone isolated
      from the sea anemone Bunodosoma caissarum.
AB  - The effects of caissarone (C8H11N5O) on guinea-pig ileum and rat duodenum
      preparations are reported. Caissarone evoked, at first, a small response, as
      compared with that of applied acetylcholine. This effect was blocked by atropine,
      hexamethonium and slightly reduced by tetrodotoxin. The main caissarone effect
      seems to be on the myenteric plexus as it increased spontaneous activity, tone
      and peristalsis; these effects being counteracted by tetrodotoxin, hexamethonium
      and atropine. Extracellular electrophysiological recording of the action
      potentials of myenteric plexus neurons showed an increase in frequency in the
      presence of caissarone. Caissarone potentiated the longitudinal muscle tension
      responses elicited by transmural electric stimulation in both control conditions,
      and when tension was reduced by pretreatment with tetrodotoxin or adenosine
      triphosphate. Caissarone also potentiated the longitudinal muscle tension
      responses to applied acetylcholine and this effect was reduced, but not
      abolished, by tetrodotoxin. Caissarone may have an indirect excitatory action on
      nicotinic receptors at the ganglia or may act as a reversible antagonist of
      purine transmitters released by neurons of the myenteric plexus involved in the
      physiological inhibition of intestinal motility.

PMID- 1979697
TI  - Inhibition of human benzylamine oxidase (BzAO) by analogues of 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine (MPTP).
AB  - A sensitive assay for human plasma BzAO, involving the conversion of 14C
      benzylamine to 14C-benzaldehyde, was developed. MPTP and several of its analogues
      were found to be competitive inhibitors of the enzyme. Ki values for the MPTP
      analogues in the presence of human plasma BzAO were determined. The analogues had
      a different rank order of inhibition of human plasma BzAO compared with the rank
      order of inhibition of bovine plasma BzAO found previously. MPTP and 1-methyl-4
      (2-methylphenyl)-1,2,3,6-tetrahydropyridine (2'-CH3-MPTP), which are potent
      nigrostriatal toxins, were weak inhibitors of human plasma BzAO.

PMID- 1979698
TI  - Drug treatment of stroke and ischemic brain: from acetylsalicylic acid to new
      drugs--100 years of pharmacology at Bayer Wuppertal-Elberfeld. Satellite
      symposium of the XIth International Congress of Pharmacology, Scheveningen, The
      Netherlands, June 28-30, 1990. Proceedings.

PMID- 1979699
TI  - Diverse mechanisms of neuronal protection by nimodipine in experimental rabbit
      brain ischemia.
AB  - The purpose of this study was to verify the possible involvement of nimodipine
      sensitive calcium channels in ischemic Ca2+ influx to hippocampal neurons to
      assess their role in nimodipine neuroprotection. We induced 15-minute global
      cerebral ischemia in pentobarbital-anesthetized and relaxed rabbits, which had
      been implanted with a transhippocampal dialysis probe, by intrathoracic artery
      occlusion combined with hypotension. A part from electroencephalographic and
      morphologic observations, changes in the extracellular concentrations of calcium,
      amino acids, and blood-brain barrier permeability to fluorescein were detected by
      microdialysis of the hippocampus. Nimodipine was applied either intravenously or
      locally to the hippocampus before, during, and after ischemia. Application of
      nimodipine locally or systemically, which had no effect on extracellular amino
      acids, enhanced recovery and normalization of the electroencephalographic
      activity and protected hippocampal neurons from early morphologic changes.
      Intravenous nimodipine reduced the ischemia-evoked drop of extracellular Ca2+ and
      completely prevented postischemic leakage of the blood-brain barrier, whereas
      local nimodipine infusion did not modify these ischemic disturbances. Our results
      suggest that nimodipine-sensitive Ca2+ channels play a minor role in the ischemic
      calcium influx to hippocampal neurons. Nimodipine, apart from a potent vasotropic
      action, may also directly protect brain neurons by intracellular calcium
      antagonism rather than by inhibition of calcium influx.

PMID- 1979700
TI  - The treatment of acute Fasciola hepatica infection in children.

PMID- 1979701
TI  - Nucleic acid probes. Proceedings of a workshop on Nucleic Acid Probes in
      Veterinary Infectious Diseases: Methods and Applications, 10 November 1988,
      Chicago.

PMID- 1979702
TI  - Characterization of Listeria monocytogenes isolates by Southern blot
      hybridization.
AB  - A synthetic deoxyribonucleotide probe for virulent Listeria monocytogenes,
      designated ADO7, was evaluated for its ability to identify restriction fragments
      of L. monocytogenes with nucleic acid sequences homologous with the beta
      hemolysin gene by Southern blot hybridization of clinical and food isolates. The
      synthetic probe hybridized with three restriction fragments (approximately 1.1,
      0.86, and 0.76 kb) of the serotype 1/2A isolates. Southern blot hybridization of
      the serogroup 4B isolates indicated that the nucleic acid sequences homologous
      with the beta-hemolysin gene probe were limited to a single restriction fragment
      of approximately 1 kb.

PMID- 1979703
TI  - Nucleic acid probe characterizes Leptospira interrogans serovars by restriction
      fragment length polymorphisms.
AB  - Restriction endonuclease analysis (REA) of genomic DNA can discriminate between
      many Leptospira interrogans serovars. However, several serovars have similar
      restriction endonuclease digestion patterns which prohibits accurate
      identification. This investigation expands previous REA studies of L. interrogans
      to include serovars in serogroup Tarassovi. Most serovars in this serogroup had
      characteristic digestion patterns by which they could be identified. However,
      four of the serovars in this serogroup had similar digestion patterns, thus
      preventing serovar identification by REA alone. To discriminate between these
      serovars REA was supplemented with Southern blot analysis. The DNA from each
      serovar showed similar but unique patterns when hybridized with a probe
      synthesized from a repetitive sequence element cloned from L. interrogans serovar
      hardjo type hardjo-bovis. The applicability of this technique to characterize
      other serogroups was assessed. One hundred sixty six of 190 serovars screened by
      Southern blot analysis contained sequences which hybridized with the repetitive
      element probe under conditions of relaxed stringency. These results suggest that
      Southern blot analysis using this probe will be a valuable supplement for typing
      L. interrogans.

PMID- 1979704
TI  - Molecular analysis of the pathogenesis of beta-cell destruction in insulin
      dependent diabetes mellitus.

PMID- 1979706
TI  - Central nervous system polyarteritis nodosa.

PMID- 1979709
TI  - 25th Conference of Higher Nervous Functions. Olomouc, Sept. 1989. Proceedings.

PMID- 1979708
TI  - Sympathomimetics for acute severe asthma: should only beta 2-selective agonists
      be used?
AB  - Sympathomimetics have become a mainstay of the treatment of acute asthma.
      Aerosolization of sympathomimetics provides as great or greater bronchodilation
      in acute severe asthma with fewer systemic effects than parenteral therapy.
      Despite the broncho-selectivity achieved with this route of administration,
      cardiostimulation remains the major, dose-limiting factor in the safe use of
      sustained, high-dose therapy with these agents. This article reviews the
      pharmacology, adverse effects, and toxicities of selected beta agonists, as well
      as clinical studies relevant to the question posed in the title. Although the
      ideal study to answer this question has not yet been performed, the authors feel
      that available evidence supports the preferential use of selective beta 2
      agonists in patients with acute, severe asthma who will require high doses of
      beta agonists.

PMID- 1979707
TI  - Neuroleptics and tardive dyskinesia--a case of iatrogenesis.

PMID- 1979710
TI  - From high flow to closed circuit anesthesia. First IFRAP symposium. Ghent, April
      28, 1990. Proceedings.

PMID- 1979705
TI  - Tardive dyskinesia.
AB  - Tardive dyskinesia is a potentially irreversible syndrome of involuntary
      hyperkinetic movements that occur in predisposed persons receiving extended
      neuroleptic (antipsychotic) drug therapy. It is usually characterized by
      choreoathetoid dyskinesias in the orofacial, limb, and truncal regions, but
      subtypes of this syndrome may include tardive dystonia and tardive akathisia.
      Although the mechanisms underlying the pathogenesis and pathophysiology of this
      disorder are unproven, altered dopaminergic functions will likely play a role in
      any explanation of it. Tardive dyskinesia develops in 20% of neuroleptic-treated
      patients, but high-risk groups such as the elderly have substantially higher
      rates. Risk factors include age, female sex, affective disorders, and probably
      those without psychotic diagnoses, including patients receiving drugs with
      antidopaminergic activity for nausea or gastrointestinal dysfunction for extended
      periods. Total drug exposure is positively correlated with tardive dyskinesia
      risk. Management strategies include a careful evaluation of both the psychiatric
      and neurologic states, a broad differential diagnosis, and adjustment of
      neuroleptic agents to the lowest effective dose that controls psychosis and
      minimizes motor side effects. No drug therapy is uniformly safe and effective for
      treating this disorder. A favorable long-term outcome of improvement or
      resolution correlates with younger age, early detection, lower drug exposure, and
      duration of follow-up.

PMID- 1979711
TI  - Restriction fragment length polymorphisms at the methylmalonyl CoA mutase locus
      in normal Chinese.
AB  - L-methylmalonyl-CoA mutase (MCM; E.C. 5,4,99,2) is the apoenzyme for catalyzing
      the isomerization of L-methylmalonyl-CoA to succinyl-CoA. Genetic deficiency of
      MCM leads to the accumulation of precursors and abnormal metabolites of L
      methylmalonyl-CoA. This can be associated with fulminant metabolic acidosis,
      widespread secondary aberrations in systemic metabolic homeostasis, mental
      retardation, or even neonatal death. This disorder is termed methylmalonic
      acidemia (MMA). This report, describes the use of an authentic, full-length
      cloned human cDNA probe, MCM26, kindly provided by Dr. Fred Ledley, for Southern
      blot analysis of genomic DNA. The pattern of EcoRI, Sac I and Hind III
      restriction endonuclease sites is reported from 14 unrelated control individuals
      of Chinese background. A Southern blot by EcoRI to the MCM26b probe reveals
      invariant bands of 4.1, 3.8, and 2.2 kb respectively. By EcoRI to the MCM26c
      probe, 7.2 kb is invariant. By HindIII to the MCM26c probe, invariant bands are
      4.8 and 2.7 kb respectively. By SacI to the MCMb probe, invariant bands are 17,
      8.0, 6.0, 3.6 and 1.8 kb respectively, while the polymorphic band is at 5.6kb.
      When combined with more diverse samples and additional polymorphisms, this
      restriction fragment length polymorphism may be useful for genetic diagnostic and
      linkage studies of MCM in MMA.

PMID- 1979712
TI  - Multiple endocrine neoplasia: how many syndromes?
AB  - The phrase multiple endocrine neoplasia (MEN) generally denotes an association of
      tumors so specific as to constitute a syndrome. Three well-recognized such
      syndromes exist. All are autosomal dominant traits and all have been tentatively
      mapped to specific chromosomes. Other purported endocrine tumor syndromes have
      been suggested either as new entities or as subtypes of the existing MEN
      syndromes. The evidence in favor of these contentions is examined critically.
      Only one "new" association, that of pheochromocytomas and islet cell tumors,
      seems reasonable, and even in this setting, some relatives have had
      manifestations of von Hippel-Lindau syndrome. There is no compelling reason why
      such conditions as von Hippel-Lindau syndrome, peripheral neurofibromatosis,
      McCune-Albright syndrome, and others should be reclassified as MEN syndromes,
      although awareness of their collective endocrine abnormalities is clinically
      important.

PMID- 1979713
TI  - Sexual discordance in monozygotic twins.
AB  - We report on monozygotic (MZ) twins who were discordant for phenotypic sex and
      Ullrich-Turner syndrome (UTS). The nonviable female was hydropic with cystic
      hygromas, ventricular septal defect, bicuspid aortic valve, polysplenia,
      intestinal malrotation, and small ovaries. The male was phenotypically normal.
      The monochorionic, diamniotic placenta had hydropic changes limited to the UTS
      infant's side. Skin samples from the infants and blood from their parents were
      obtained for cytogenetic and molecular analysis. Karyotypes of the twins were
      45,X and 46,XY. Quinacrine polymorphisms on 7 chromosomes and RFLP analysis at 8
      loci showed complete identity. MZ twins discordant for phenotypic sex have been
      described previously. Most of these show evidence of mosaicism in a 45,X patient
      with a normal 46,XY cell line, and a normal 46,XY male. While the issue of
      mosaicism in our case cannot be fully resolved, no mosaicism was found in 50
      cells analyzed cytogenetically from each culture or by PCR analysis of a Y
      specific sequence. The twins probably originated from either postzygotic
      nondisjunction or anaphase lag, followed or accompanied by twinning. The
      discordant placental morphology suggests an embryonic origin of at least part of
      the placental mesenchymal core.

PMID- 1979715
TI  - Somatostatin increases voltage-dependent potassium currents in rat somatotrophs.
AB  - To study the modulatory effects of somatostatin on membrane K+ currents, whole
      cell voltage-clamp recordings were performed on identified rat somatotrophs in
      primary culture. In the presence of Co2+ (2 mM) and tetrodotoxin (1 microM) in
      the bath solution to block Ca2+ and Na+ inward currents, two types of voltage
      activated K+ currents were identified on the basis of their kinetics and
      pharmacology. First, a delayed rectifier K+ current (IK) had a threshold of -20
      mV, did not decay during voltage steps lasting 300 ms, and was markedly
      attenuated by extracellular application of tetraethylammonium (TEA, 10 mM).
      Second, a transient outward K+ current (IA) was activated at -40 mV (from a
      holding potential of -80 mV) and persisted despite the presence of TEA. This IA
      was blocked by 4-aminopyridine (2 mM). Somatostatin (10 nM) increased IK by 75%
      and IA by 45% without obvious effects on steady-state voltage dependency of
      activation or inactivation, and these effects were reversible. This increase in
      K+ currents may contribute in part to the inhibitory effect of somatostatin on
      growth hormone release.

PMID- 1979714
TI  - Proliferation markers Ki-67 and p105 in soft-tissue lesions. Correlation with DNA
      flow cytometric characteristics.
AB  - Frozen tissue immunoreactivity with Ki-67, a monoclonal antibody that recognizes
      a nuclear antigen in nonresting or proliferating cells, was compared to DNA flow
      cytometry results (from fresh tissue) in a diverse group of 60 soft-tissue
      lesions. Both DNA index and Ki-67 score were independently reported to be
      associated with grade and prognosis in sarcomas, but no direct comparison of
      these two variables was made. It was attempted to measure proliferative activity
      in fixed paraffin-embedded tissues immunohistochemically in a subset of lesions
      using an antibody to another nuclear proliferation antigen, p105. Lesions were
      given a grade according to lesion category (reactive, 1; benign, 2; low-grade
      malignant, 3; and high-grade malignant, 4). Ki-67 reactivity correlated
      relatively well with this grading system (r = 0.59); benign lesions usually
      exhibited a low Ki-67 score and malignant lesions usually but not always
      exhibited a high score. For example, some malignant fibrous histiocytomas
      contained only rare positive cells. Some disparity between Ki-67 score and grade
      and within histologic types indicates some independence from these features, a
      fact that may be important when correlation with prognosis is performed. However
      Ki-67 did not correlate well with flow data such as percentage S phase (r =
      0.30), percentage S + G2M phases (r = 0.37), or DNA index (r = 0.39). This
      probably is due to the fact that Ki-67 also marks cells in the G1 phase, whereas
      these are excluded in flow data analyses. Anti-p105 highlighted almost all nuclei
      in all cases tested, including fibromatosis, and did not correlate with Ki-67
      score, histologic grade or DNA flow cytometric data. Results with p105 could not
      be favorably affected by titration experiments. It is reasonable to conclude that
      the Ki-67 score is a variable related to but independent of histologic grade,
      histologic type, and DNA flow values. Whether it is prognostically important in
      human sarcomas, as has been suggested, awaits further clinicopathologic study.

PMID- 1979716
TI  - Distribution and ontogeny of thyrotropin-releasing hormone degrading enzymes in
      rats.
AB  - The distribution and ontogeny of tissue prolyl endopeptidase and pyroglutamyl
      peptidase I activities were studied in the rat from the 7th day before birth to
      adulthood. While low levels of prolyl endopeptidase activity were demonstrable in
      many fetal tissues, activity in brain cortex, hypothalamus, lung, and kidney
      increased dramatically during the 2 wk after birth, gradually returning to adult
      levels. In adult rats, levels of tissue prolyl endopeptidase activity were
      highest in kidney, when compared with the intermediate levels in brain cortex,
      hypothalamus, and liver. Pyroglutamyl peptidase activity was widely distributed
      in adult rat tissues with high levels in kidney and liver that exceeded
      intermediate levels in brain cortex and hypothalamus. Pyroglutamyl peptidase
      activities in fetal gut, brain, and lung tissue were elevated above adult values.
      In contrast to the development changes in prolyl endopeptidase activities,
      pyroglutamyl peptidase activity remained elevated above adult levels only during
      the first week of life. These results indicate that both prolyl endopeptidase and
      pyroglutamyl peptidase activities in the rat are developmentally regulated.

PMID- 1979717
TI  - Cimaterol reduces cathepsin activities but has no anabolic effect in cultured
      myotubes.
AB  - The effect of the beta-adrenergic agonist cimaterol on bovine and chicken primary
      myotubes was assessed. Cimaterol at 10-100 nM concentrations reduced cathepsin B
      benzyloxy-carbonyl-Arg-Arg-4-methyl-7-coumarylamide hydrolyzing activity, as well
      as benzyloxycarbonyl-Phe-Arg-4-methyl-7-coumarylamide hydrolysis, which is a
      substrate for both cathepsin B and cathepsin L. Maximum effect was observed after
      6-16 h treatment. Cathepsin H Arg-4-methyl-7-coumarylamide hydrolyzing activity
      was low and not significantly affected by cimaterol treatment. Despite decreasing
      cathepsin activities, cimaterol also increased proteolysis rates but induced no
      detectable effect on protein synthesis rates. These observations suggest that
      beta-agonists, as a result of a direct action on muscle, can decrease cathepsin
      activities but that beta-agonist-induced muscle hypertrophy may not be due to a
      direct effect on muscle cells.

PMID- 1979718
TI  - Characterization of the opioid receptor type mediating inhibition of rat gastric
      somatostatin secretion.
AB  - The opioid peptides are potent inhibitors of gastric somatostatin-like
      immunoreactivity (SLI) secretion from the isolated perfused rat stomach. In
      addition, inhibition of SLI secretion induced by vagal stimulation is partially
      blocked by naloxone, indicating that endogenously released opioid peptides
      probably play a physiological role in the regulation of SLI release. The opioid
      peptides exert their effects by interacting with a number of different receptor
      types. In the present study, the effect of the selective delta-opioid receptor
      agonists [D-Pen2.5]enkephalin and [D-Pen2,L-Pen5]enkephalin and the mu-receptor
      agonist [D-Ala2, N-methyl (NMe)-Phe4,Gly5-ol]enkephalin on gastric inhibitory
      polypeptide (GIP)-stimulated SLI secretion from the isolated perfused rat stomach
      have been studied. Responses to the less selective delta-agonist [D-Ala2,D
      Leu5]enkephalin, dynorphins 1-8, 1-13, and 1-17, and the extended enkephalin
      forms Met-enkephalin-Arg6-Phe7,Met- enkephalin-Arg6-Gly7-Leu8, and Met-enkephalin
      Arg6-Arg7-Val8-NH2 (metorphamide), have also been investigated. [D-Ala2,NMe
      Phe4,Gly5-ol]enkephalin induced a concentration-dependent inhibition of GIP
      stimulated SLI secretion, with 50% of maximal inhibition at 10 nM. Neither [D
      Pen2.5]enkephalin nor [D-Pen2,L-Pen6]enkephalin (10 nM to 1 microM) had any
      effect on SLI release, and [D-Ala2,D-Leu5] enkephalin inhibited SLI release only
      at high concentrations. Met-enkephalin-Arg6-Phe7 and metorphamide both inhibited
      SLI release, whereas Met-enkephalin-Arg6-Gly7-Leu8 and the dynorphins had little
      or no effect. In conclusion, the strong inhibition of SLI secretion produced by
      [D-Ala2,NMe-Phe4,Gly5-ol] enkephalin and lack of major effect of [D-Pen2.5]
      enkephalin, [D-Pen2,L-Pen5]enkephalin, and the dynorphins indicate that opioid
      peptide-induced inhibition was mediated by interaction with mu-receptors and that
      neither delta or kappa-receptors play a significant role.

PMID- 1979719
TI  - Inhibition of proximal tubule Na(+)-K(+)-ATPase activity requires simultaneous
      activation of DA1 and DA2 receptors.
AB  - This study examines the receptor mechanisms by which dopamine (DA) inhibits Na(+)
      K(+)-adenosinetriphosphatase (ATPase) activity in single permeabilized proximal
      tubule (PCT). Na(+)-K(+)-ATPase activity was inhibited in the presence of both
      DA1- and DA2-specific agonists but not by either agonist alone. The inhibition
      induced by DA (10(-6) M) was attenuated in the presence of either of the two DA2
      specific antagonists S-sulpiride and YM 09151 at 10(-5) M and in the presence of
      the DA1 antagonist SCH 23390 (10(-5) M). PCT adenosine 3',5'-cyclic monophosphate
      (cAMP) levels were significantly increased in the presence of DA and DA1 agonist,
      but DA2 agonist had no effect on cell cAMP levels. Na(+)-K(+)-ATPase activity was
      significantly inhibited in PCT incubated with DA2 agonist (10(-5) M) and
      dibutyryl (DB)-cAMP (10(-6) M) but not with DA2 agonist (10(-5) M) only. PCT
      Na(+)-K(+)-ATPase activity was also significantly inhibited in the presence of
      both DA2 agonist (10(-5) M) and forskolin (10(-6) M). Neither DBcAMP (10(-6) M)
      nor forskolin (10(-6) M) alone inhibited Na(+)-K(+)-ATPase activity. In tubules
      incubated with DA (10(-8) to 10(-9) M), the presence of DBcAMP (10(-6) M)
      enhanced the sensitivity by which DA inhibited Na(+)-K(+)-ATPase activity. We
      conclude that PCT Na(+)-K(+)-ATPase activity is inhibited by a synergistic action
      of the DA1 and DA2 receptors, with the DA1 receptor acting to increase cell cAMP
      levels.

PMID- 1979720
TI  - Ontogeny of DA1 receptor-adenylate cyclase coupling in proximal convoluted
      tubules.
AB  - The natriuretic effect of dopamine (DA) is less in younger than in older animals.
      The natriuretic (DA) is less in younger than in older animals. The natriuretic
      effect of DA is due in part to occupation of renal tubular DA1 receptors, which
      are most abundant in the proximal convoluted tubule (PCT). However, it has not
      been determined whether ontogenic differences in DA1-receptor density, affinity,
      or coupling to intracellular second messengers are involved in the reduced
      natriuretic effect of DA in the young animal. We therefore studied the DA1
      receptor by radioligand binding with the DA1 antagonist 125I-SCH 23982 and the
      effect of DA1 agonists and guanine nucleotides on adenylate cyclase (AC) activity
      in microdissected PCT during development in Wistar-Kyoto rats (WKY). The
      dissociation constant (Kd) and maximum receptor density (Bmax) were similar in
      all groups (Kd, in nM: 11.9 +/- 0.7 at 3 wk, 10.6 +/- 0.4 at 8 wk, and 12.2 +/-
      1.2 at 20 wk; Bmax, in fmol/mm PCT: 0.24 +/- 0.02 at 3 wk, 0.23 +/- 0.01 at 8 wk,
      and 0.24 +/- 0.01 at 20 wk). Basal AC activities were similar, and forskolin (10(
      5) M), which directly stimulates AC, increased AC activity to a similar extent in
      all age groups. However, the DA1 agonists, fenoldopam (10(-5) M) and SND-919-CL2
      (10(-6) M), increased AC activity in PCT to a greater extent in 20-wk-old (55 +/-
      7%) than in 3-wk-old rats (27 +/- 1%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1979721
TI  - Nicotine-induced skeletal muscle vasodilation is mediated by release of
      epinephrine from nerve terminals.
AB  - To determine the role of sympathetic innervation on nicotine-induced alterations
      in peripheral (hindlimb) blood flow in the pentobarbital-anesthetized dog, one
      hindlimb was acutely denervated and remained attached to the body by only the
      femoral artery and vein, whereas the contralateral limb remained innervated and
      intact. Measurements were made of aortic pressure, femoral artery and venous
      pressures, femoral artery flow, and plasma catecholamine levels during
      intravenous systemic infusion of nicotine. The response to nicotine (9-36
      micrograms.kg-1.min-1) on the denervated side was a transient increase followed
      by a persistent decrease in flow and increase in vascular resistance. The
      response in the innervated limb was a large increase in blood flow and decrease
      in vascular resistance. The vasoconstrictor and vasodilator responses could be
      abolished by pretreatment with both propranolol and phentolamine. The vasodilator
      response could not be abolished by cholinergic or histaminergic receptor
      antagonism. Hexamethonium abolished all systemic and peripheral responses to
      nicotine. Desipramine selectively abolished the vasodilator response in the
      innervated hindlimb. The vasodilator and vasoconstrictor responses could be
      mimicked with systemic or local administration of epinephrine. We conclude that,
      in the hindlimbs of dogs, nicotine stimulates the release of epinephrine from
      nerve terminals and/or tissue stores to activate beta 2-adrenoceptors and promote
      vasodilation in skeletal muscle of innervated preparations.

PMID- 1979722
TI  - Functional, physical, and ultrastructural localization of CD15 antigens to the
      human polymorphonuclear leukocyte secondary granule.
AB  - A murine monoclonal IgM antibody, M3, which interferes with both
      polymorphonuclear leukocyte (PMN) phagocytosis and bactericidal activity, was
      used to examine the subcellular location of antigens bearing 3-fucosyllactosamine
      (CD15 antigens) within this cell type. Percoll gradient-separated secondary
      granule fractions were rich in CD15 antigens, with at least seven antigens
      recognizable in SDS-PAGE/electroblot studies. Sonication/sedimentation
      experiments using secondary granule fractions showed that both soluble and
      sedimentable CD15 antigens were present. Exposure of purified PMN to the
      secondary granule secretagogue phorbol myristate acetate caused extracellular
      release of two or three CD15 antigens, which could be purified by
      immunoprecipitation using antibody M3. Triton X-114 phase-partition experiments
      showed that secondary granule fraction CD15 antigens could be partitioned into
      hydrophilic (aqueous phase) and hydrophobic (detergent phase) antigens,
      suggesting that several of these antigens were integral secondary granule
      membrane components. Ultrastructurally, PMN intracellular granules showed two
      patterns of CD15 expression, localization over both granule matrix/granule
      membrane and localization to only granule membrane. Colocalization studies showed
      that lactoferrin and CD15 antigens were both present in a subset of intracellular
      granules, confirming a secondary granule location for these antigens.

PMID- 1979723
TI  - A comparison of neurological, metabolic, structural, and genetic evaluations in
      persons at risk for Huntington's disease.
AB  - We compared four diagnostic data sets for the assessment of individuals at risk
      for Huntington's disease. Fifty-four chorea-free persons were evaluated by
      neurological examination, positron emission tomography measurement of glucose
      metabolism, radiographic computerized tomographic measurement of caudate size,
      and genetic testing at the polymorphic DNA loci D4S10, D4S43, and D4S125. Twelve
      (22%) persons had abnormal caudate metabolism, 6 (11%) had subtle abnormalities
      of motor control, and 7 (13%) had computed tomographic evidence of caudate
      atrophy, compared with an expected gene frequency of 34% for this population. In
      20 persons with unambiguous genetic test results or the subsequent phenotypic
      expression of Huntington's disease (chorea), there was a greater sensitivity of
      the positron emission tomographic measurement of caudate metabolism (75%)
      relative to computed tomography (33%) or the clinical examination (17%) for the
      determination of a subpopulation of probable Huntington's disease gene carriers.
      Hypometabolism of the putamen and globus pallidus, and hypermetabolism of the
      precentral gyrus were also associated with a high probability of carrying the
      Huntington's disease gene. The findings support the hypothesis that abnormalities
      of cerebral metabolism precede clinical or structural (computed tomographic)
      abnormalities in gene-positive individuals at risk for Huntington's disease.

PMID- 1979724
TI  - Dystrophin analysis in Duchenne and Becker muscular dystrophy carriers:
      correlation with intracellular calcium and albumin.
AB  - Immunocytochemical localization and immunoblot analysis of dystrophin in muscle
      fibers of 11 obligate and probable, and 7 possible carriers of Duchenne and
      Becker muscular dystrophy revealed an abnormal expression of the protein in 3 of
      them. Localization of calcium and albumin, as endogenous markers of extracellular
      fluid penetration, showed the presence of both molecules inside some fibers
      lacking dystrophin. Our morphological studies show that the initial stages
      leading to fiber necrosis in Duchenne muscular dystrophy are present in carriers
      with mosaicism. Comparison of dystrophin studies with restriction fragment length
      polymorphism analysis and creatine kinase levels showed that neither
      immunocytochemical nor immunoblot techniques for dystrophin are sensitive enough
      to provide a basis for genetic counseling.

PMID- 1979725
TI  - [Peripheral blood stem cell autografts in pediatric cancer].
AB  - Harvest of peripheral blood stem cells (PBSC) for autografts is a safe, reliable
      procedure with low morbidity in children with cancer, and cryopreserved PBSC are
      useful in reducing cytopenia following marrow-ablative chemotherapy. The colony
      forming unit granulocyte/macrophage (CFU-GM) content of the thawed grafts is an
      important determinant of hematopoietic recovery after PBSC autografts. The
      possible value of high-dose chemotherapy without total body irradiation and PBSCT
      compared to intensified chemotherapy in the treatment of children with very high
      risk lymphoid malignant disorders was reported.

PMID- 1979726
TI  - [Chromosome abnormalities and tumor suppressor gene in childhood cancer].
AB  - Retinoblastoma gene has been cloned, and gene product has been characterized
      precisely. Recently, Wilms' tumor gene has been cloned, and interestingly, its
      expression was found in genitourinary system, suggesting that anomaly of this
      system was due to WT gene itself. Molecular analysis performed in colon cancer
      suggested that several tumor suppressor genes were involved in carcinogenesis and
      progression of this tumor. These findings revealed that tumor suppressor genes
      were involved in the development of adult cancer as well as childhood embryonal
      tumors. Chromosome abnormalities and tumor suppressor gene in childhood cancer
      are reviewed and referred to future prospects.

PMID- 1979727
TI  - Etretinate suppresses ICAM-1 expression by lesional keratinocytes in healing
      cutaneous lichen planus.

PMID- 1979728
TI  - [Outcome of "white coat reaction" induced by nurse and physician in patients with
      hypertension treated with a beta blockader (bisoprolol)].
AB  - The aim of the study was to assess the evolution of Alerting reaction (AR) under
      beta blocker treatment and to discuss its incidence on the management of arterial
      hypertension (AH). In 28 patients (pts), 19 men, 9 females, 46 +/- 12 years old,
      suffering from a mild to moderate AH, blood pressure (BP) was measured, according
      to a ritual circuit by a nurse (N), then a 12-minutes recorded monitoring, then a
      physician (Ph) using a mercury sphygmomanometer in upright, then in supine
      position at the end of the visit (165 +/- 18/108 +/- 13 mmHg, 161 +/- 14/100 +/-
      9 mmHg). Pts received a cardioselective beta blocker, bisoprolol (B), 10 mg once
      daily and BP was evaluated after 1 and 2 months (D30; D60) under identical
      conditions. When compared to monitoring BP, there was a significant increase in
      systolic (S) and diastolic (D) BP, taken by the nurse and the physician,
      attributed to AR (delta SBP; delta DBP). Under B, AR remained unchanged, even
      increased regarding upright DBP at D30, D60 in spite of its efficacy: (formula;
      see text) The study demonstrates that there is no incidence of beta blocker on
      alerting reaction and that AR must be considered to evaluate the treatment and
      avoid an unnecessary or overtreatment. In case of discrepancies, it is suggested
      to perform an ambulatory BP monitoring.

PMID- 1979729
TI  - [Renal effects of intravenous tertatolol in essential arterial hypertension].
AB  - The acute renal effects of intravenous tertatolol were studied in eight patients
      with moderate essential hypertension: the study included a 100 mmol/day sodium
      intake during 3 days. Then, tertatolol was infused after a water load during 2
      consecutive periods of 30 min (priming dose followed by constant infusion) in
      order to obtain plasma concentrations of tertatolol at 2 different levels: 10
      ng/ml, then 40 ng/ml successively; the measurements were obtained at 15, 30, 45
      and 60 min. The renal plasma flow (RPF) and the glomerular filtration rate (GFR)
      were calculated from the 131I-Hippuran clearance and the 125I-Iothalamate
      clearance respectively; a bladder catheter allowed a precise urine collection.
      The results indicate that intravenous tertatolol, at low dose, induced a marked
      and early renal vasodilatation; higher dose of tertatolol attenuated the
      vasodilator response, probably because of a decrease in cardiac output (suggested
      by the decrease in heart rate); thus, the systemic effects would hide the direct
      renal hemodynamic effects of tertatolol. Natriuresis and kaliuresis were
      unchanged by intravenous tertatolol.

PMID- 1979730
TI  - [Binding sites of imidazolines. Study with (3H)-idazoxan in renal cortex of Sabra
      salt-sensitive (SBH) and salt-resistant (SBN) rats].
AB  - Imidazoline binding sites have been characterized in organs modulating blood
      pressure, such as brain and kidney with (3H)-p-aminoclonidine and (3H)-Idazoxan
      respectively. However, the pharmacological characteristics of the imidazoline
      preferring binding sites differ considerably depending on the species
      investigated and the radioligand used. Little is known about the physiological
      relevance of the non-adrenergic (3H)-idazoxan binding sites. As some imidazolines
      and certain alpha-adrenoceptor agonists possess antihypertensive activity, an
      alteration of these binding sites should be considered as a possible causes in
      the development of hypertension. In the present study, we performed binding
      studies with the imidazoline ligand (3H)-idazoxan in renal cortex of hypertensive
      salt-sensitive (SBH) and normotensive salt-resistant (SBN) Sabra rats. (3H)
      idazoxan binding capacities were higher in SBH than in SBN rats. Competition
      studies have shown for (3H)-idazoxan specific binding non-adrenergic
      characteristics exclusively. In these both substrains, (3H)-idazoxan binding
      exhibit pharmacological profile of imidazoline binding sites. However, theses
      sites have also high affinity for guanidino compounds and amiloride.
      Surprisingly, amiloride and some analogues were significantly more potent in SBN
      than in SBH rats. From this study, it is difficult to elucidate the physiological
      role of imidazoline binding sites in renal cortex. However, differences observed
      between SBN and SBH suggest that these sites may play a role in the development
      of hypertension in Sabra rats.

PMID- 1979731
TI  - [Selectivity of a new antihypertensive agent, rilmenidine, for imidazoline
      receptors in the human brain].
AB  - The involvement of the central nervous system in the global hypotensive effect of
      rilmenidine (R) was already suspected after experiments on cats and dogs. Indeed,
      the injection of this drug in the vertebral artery provoked a decrease in the
      arterial blood pressure in these two species. Recently, we showed that
      intracisternal injections of cumulative doses (1 to 300 micrograms/kg) in
      anaesthetized rabbits significantly lowered the blood pressure. In that protocol
      the efficient dose 20% was 1.5 micrograms/kg when it was 70 micrograms/kg for
      intravenous injections. The hypotension was always associated with bradycardia.
      Thus we confirmed that the drop in the arterial blood pressure induced by R was,
      at least partially, due to a central inhibition of the vasomotor tone. When we
      pretreated anaesthetized rabbits, always by intracisternal injections, with
      identical doses of yohimbine or idazoxan (5 nmoles/kg), we observed that idazoxan
      prevented much more the hypotensive effects of R than yohimbine. This study
      demonstrated that R whose chemical structure is close to that of imidazolines was
      much better antagonized by a substance with an imidazoline-like structure than by
      a classical alpha 2-antagonist. These results were confirmed by binding studies
      realized with human brain membranes. Tritiated clonidine was bound to cortical
      membrane preparations, containing mainly alpha 2-adrenoceptors, as well as to
      medullary membrane preparations, containing mainly imidazoline receptors. We
      observed that R selectivity for the medullary imidazoline preferring receptors
      was 2.5 times higher than that of the reference substance, clonidine. So, it
      seems that the central hypotensive effect of R might be related to its
      interaction with imidazoline specific receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1979732
TI  - The action of prolyl-leucyl-glycinamide (PLG) on the nigrostriatal pathway of the
      rat.
AB  - In order to study the nigrostriatal pathway, we obtained the rotatory behavior
      model in male Wistar rats by electrolytic lesion of the left lateral hypothalamic
      region. Animals thus lesioned displayed rotations toward the same side of lesion
      when apomorphine was administered, a result in disagreement with what has been
      obtained in the model with 6-hydroxydopamine lesion. The administration of PLG
      alone was not followed by rotatory behavior but when the compound was
      administered in low doses (0.25 to 1mg/kg) simultaneously with apomorphine to
      animals previously submitted to REM sleep deprivation, a significant increase in
      the number of rotations was observed in comparison with controls and groups
      receiving higher doses of PLG. These results indicate that PLG may act as a
      modulator on dopamine receptors in the striatum.

PMID- 1979733
TI  - Examination of the conformational meaning of "delta-address" in the
      dermenkephalin sequence.
AB  - Comprehensive energy calculations were applied to four opioid-related peptides
      with different receptor selectivities, namely the delta-selective dermenkephalin
      (Tyr-D-Met-Phe-His-Leu-Met-Asp-NH2, DRE), the mu-selective dermorphin (Tyr-D-Ala
      Phe-Gly-Tyr-Pro-Ser-NH2, DRM) and their "hybrid" peptides DRM/DRE (Tyr-D-Ala-Phe
      Gly-Leu-Met-Asp-NH2) and DRE/DRM (Tyr-D-Met-Phe-His-Tyr-Pro-Ser-NH2). It was
      shown that the N-terminal tripeptide "mu-messages" in the delta-selective ligands
      DRE and DRM/DRE can possess similar low energy space arrangements of their
      functionally important elements (the N-terminal alpha-amino group and the
      aromatic moieties of Tyr and Phe), but that these are different from the space
      arrangement of these moieties in mu-selective DRM and DRE/DRM. These results
      suggest that the C-terminal tripeptide "delta-address" in DRE may influence the
      conformation of the "mu-message" in DRM. A refined model for the delta-receptor
      bound conformation of DRE is proposed based on these calculations which is
      similar to that previously suggested for the cyclic delta-selective peptide [D
      Pen2, D-Pen5]enkephalin (DPDPE). This model also has partial correspondence with
      the structure of the delta-selective alkaloid naltrindole.

PMID- 1979734
TI  - Targeting of antiviral drugs to T4-lymphocytes. Anti-HIV activity of
      neoglycoprotein-AZTMP conjugates in vitro.
AB  - The delivery of the anti-HIV agent 3'-azido-3'-deoxythymidine (AZT), in its 5'
      monophosphate form, (in) to human T-lymphocyte MT-4 cells in vitro through
      covalent coupling to neoglycoproteins was investigated. In vivo application of
      this drug targeting concept may lead to increased efficacy and/or diminished side
      effects caused by AZT during the treatment of AIDS and ARC patients. The
      rationale for the design of the neoglycoprotein carriers is based on the
      existence of sugar recognizing lectins on T-lymphocytes. Using a phenyl-linkage
      between sugar and Human Serum Albumin (HSA), various mannose-, fucose-, galactose
      and glucose-containing neoglycoproteins were synthesized. The intrinsic anti-HIV
      activity of these neoglycoproteins was tested in vitro in HIV-1 infected MT-4
      cells. Only the derivative having 40 moles mannose per mole protein (Man40HSA)
      shows pronounced anti-HIV-1 activity itself. This effect may be caused by
      interference of the Man40HSA with the gp120-CD4 mediated virus/MT-4 cell
      interaction. After conjugation with AZTMP, the mannose- as well as the fucose-
      and galactose-containing conjugates exhibited a pronounced activity. Conjugates
      of glucose-HSA and HSA displayed much less activity in spite of the fact that
      drug loading was considerably higher, compared with the galactose, mannose and
      fucose derivatives. In the series of mannose-neoglycoproteins, the Man22HSA-AZTMP
      conjugate was shown to be more than 30 times as active against HIV-1 compared to
      HSA-AZTMP. Selectivity indices of Man7 and Man22HSA-AZTMP were exceeding the AZT
      and AZTMP indices, indicating that these conjugates possess a more selective
      action. Stability experiments indicate that the potent action of the galactose-,
      mannose- and fucose-HSA-AZTMP conjugates is not due to a complete extracellular
      hydrolysis of the covalent drug-protein bond. Since Man22HSA has no intrinsic
      activity in the concentration range used, the antiviral effect is unlikely to be
      explained by synergism of the neoglycoprotein by a component of the cell membrane
      and subsequent internalization and release of the drug from the conjugate may
      play a role.

PMID- 1979735
TI  - Evidence for impaired mitoxantrone and vinblastine binding in P388 murine
      leukemia cells with multidrug resistance.
AB  - Multidrug resistance is associated with a P170 glycoprotein efflux pump that
      limits net drug accumulation in resistant cell lines. Other evidence has
      suggested that diminished net drug uptake in multidrug resistant (MDR) cells is
      due to decreased drug binding as well. To assess the contribution of binding
      differences to net drug accumulation and retention in MDR cells, mitoxantrone and
      vinblastine, two agents commonly associated with the MDR phenotype but with
      different mechanisms of action and intracellular binding sites, were studied in
      P388 murine leukemia cells. For both drugs, resistance was associated with a
      marked reduction in tightly bound drug which can account for the diminished net
      drug accumulation in this cell line; even at 1 microM vinblastine when the
      exchangeable component was one-half that of the sensitive cells, the
      nonexchangeable component was only one-seventh. For mitoxantrone, the
      exchangeable drug component was greater in resistant cells at low drug levels (1
      microM) and similar at high drug levels (10 microM). For vinblastine, the
      exchangeable drug component was decreased in the resistant cells at 1 microM, but
      the difference compared to sensitive cells became neglible at 10 microM. The data
      indicate that diminished net drug uptake in the P388 MDR cell line was associated
      with a marked decrease in tightly bound, i.e. nonexchangeable, drug fractions for
      both mitoxantrone and vinblastine. Therefore, alterations in intracellular
      binding are in important factor in the decreased cellular uptake and retention of
      drugs in the multidrug resistance phenomenon. The relationship between these
      changes and the P170 efflux pump requires further clarification.

PMID- 1979736
TI  - Vasoactive intestinal peptide (VIP) activation of nuclear protein kinase C in
      purified nuclei of rat splenocytes.
AB  - We have examined the actions of vasoactive intestinal peptide (VIP) and certain
      other known immune modulators on a nuclear pool(s) of protein kinase C (PKC) in
      isolated rat splenocyte nuclei. Rat splenocyte nuclei pure by enzymatic and
      electron microscope criteria demonstrated a time- and concentration-dependent
      activation of nuclear PKC (nPKC) by VIP. A biphasic pattern of three bell-shaped
      curves was observed with peak phosphorylation at 10(-15), 10(-9) and 10(-6)M VIP.
      The phosphorylation of endogenous nuclear substrates was characterized as a PKC
      mediated event by use of three known PKC inhibitors, 1-(5-isoquinolinylsulfonyl)
      2-methylpiperazine (H-7), sphingosine, and staurosporine, which produced similar
      phosphate incorporation measurements. Also, this activity was blocked with the
      addition of a monoclonal antibody to PKC. Inhibitors of the ability of VIP to
      activate nPKC included somatostatin, 8-bromo-cAMP, peripheral benzodiazepine
      receptor modulators, and the PKC inhibitors, sphingosine and staurosporine. These
      data have direct relevance to our knowledge of cell-mediated immunity.

PMID- 1979738
TI  - Highlights of the second international conference on systemic lupus
      erythematosus.

PMID- 1979737
TI  - Increased expression of intercellular adhesion molecule 1 on the fibroblasts of
      scleroderma patients.
AB  - The surface expression of intercellular adhesion molecule 1 (ICAM-1) and class I
      and class II major histocompatibility complex molecules on cultured dermal
      fibroblasts from 7 scleroderma patients and 6 control donors was compared.
      Scleroderma fibroblast lines contained 41.0 +/- 3.0% (mean +/- SEM) cells with
      high levels of ICAM-1 expression (ICAM-1-high), whereas 26.9 +/- 1.5% of control
      fibroblasts were ICAM-1-high (P = 0.0003). There were no differences in the
      expression of class I and class II molecules. ICAM-1-high and ICAM-1-low
      fibroblasts produced equal amounts of total protein and procollagen. The increase
      in the number of ICAM-1-high fibroblasts in scleroderma patients may facilitate T
      cell activation and lymphokine production, and thus indirectly contribute to the
      fibrotic process.

PMID- 1979739
TI  - Antineutrophil cytoplasmic antibodies in polyarteritis nodosa related to
      hepatitis B virus.

PMID- 1979740
TI  - Plasmid analysis and restriction fragment length polymorphisms of chromosomal DNA
      allow a distinction between Borrelia burgdorferi strains.
AB  - We examined the relationships of the genomes of five strains of Borrelia
      burgdorferi isolated from ticks, two from North America, including the type
      strain B31, and three from Switzerland. We determined restriction fragment length
      polymorphisms by using eight cloned DNA fragments as hybridization probes to
      genomic Southern blots. Two divergent patterns were observed, represented by B31
      and one Swiss strain on the one hand and the two other Swiss strains on the
      other. The second American strain resembled B31. One of the DNA probes allowed
      distinction between the closely related strains within a group. The close
      resemblance of one Swiss strain to the North American strains suggests the
      possibility of their European origin. All five strains carried a circular plasmid
      of about 29 kb, and three contained an additional species of about 9 kb, both of
      which exhibited homology between the strains. The profiles of linear plasmids
      revealing species of 5.1 kb to 58 kb reflected the polymorphisms of chromosomal
      DNAs. Linear plasmids of similar size shared DNA sequence homology. Some of the
      smaller plasmids tended to become lost during cultivation.

PMID- 1979741
TI  - Organization and nucleotide sequence of the 3' end of the human CAD gene.
AB  - Aspartate transcarbamylase (ATCase) is found as a monofunctional protein in
      prokaryotes and as a part of a multifunctional protein in fungi and animals. In
      mammals, this enzyme along with carbamyl phosphate synthetase II and
      dihydroorotase (DHOase) is encoded by a single gene called CAD. To determine the
      relationship between gene structure and the enzymatic domains of human CAD, we
      have isolated genomic clones of the human gene and sequenced the region
      corresponding to the 3' end of the gene. This includes exons encoding the end of
      the domain for DHOase, the complete domain for ATCase, and the bridge region
      connecting the two enzymatic domains. Three findings emerged. First, in comparing
      the human coding sequence to that obtained for other species that have a CAD
      gene, the length of the bridge region is conserved but its sequence is not. This
      is in contrast to the strong degree of positional identity observed for the
      segments of CAD encoding the DHOase and ATCase domains. Second, sets of exons
      appear to correspond to specific domains and subdomains of the encoded protein.
      Third, while overall there is a strong conservation of protein sequence among the
      ATCases of all species, reflecting conservation in catalytic function, two
      particular regions of the enzyme are more highly conserved among species where
      ATCase is a domain of a multifunctional protein as opposed to species where it is
      a monofunctional protein. Such findings may indicate regions of the ATCase domain
      that provide important structural contacts or functional channels when part of a
      multifunctional protein.

PMID- 1979742
TI  - Characterization of three distinct size classes of human 3-hydroxy-3
      methylglutaryl coenzyme A reductase mRNA: expression of the transcripts in
      hepatic and nonhepatic cells.
AB  - 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase mRNA is expressed in
      two highly differentiated human hepatoma cell lines, HepG2 and Hep3B, at
      exceptionally high levels relative to human fetal liver and fibroblasts. Blotting
      experiments revealed that the mRNA consists of three major size classes of
      approximately 4.7, 4.5, and 4.2 kb that responded coordinately to agents that
      alter HMG-CoA reductase activity. In view of the markedly elevated levels of
      reductase mRNA in the hepatoma cell lines, we compared the pattern of
      transcriptional initiation in these cells with those in normal liver and
      fibroblasts. These analyses revealed a complex pattern of initiation sites, all
      of which were suppressed by oxysterols, extending over approximately 300
      nucleotides. However, all of the major sites detected in the hepatomas could also
      be found in human liver and fibroblasts. Heterogeneity of transcriptional
      initiation does not account for the three major size classes of mRNA detected by
      RNA blotting. RNase H mapping demonstrates that these are produced by use of
      three polyadenylation sites. To determine the extent to which these sites have
      been conserved between the human gene and the previously characterized Chinese
      hamster gene, we cloned and sequenced the 3' untranslated region of the longest
      form of the human mRNA. These studies revealed that, despite a high overall
      degree of sequence conservation, the spectrum of polyadenylation sites used
      differs qualitatively between the two species. Features of the mRNA sequence that
      may contribute to these differences are described.

PMID- 1979743
TI  - Immunological and serological markers predictive of progression to AIDS in a
      cohort of HIV-infected drug users.
AB  - We have performed a prospective 33-month follow-up of the evolution of HIV
      infection in a cohort of 76 HIV-positive intravenous drug users (IVDUs). We
      report on immunological and serological variables that proved to be highly
      predictive of development to AIDS. In a stepwise multivariate analysis of the
      actuarial progression rate we found the number of CD4+ lymphocytes to be the most
      powerful predictor of progression to AIDS. We found no independent predictive
      effects associated with any other variable with predictive power: loss of
      antibody to p24 antigen, anergy, HIV p24 antigenaemia, loss of antibody to p53
      (reverse transcriptase), decreased number of CD8+ T cells, loss of antibody to
      p31, loss of antibody to p17, beta 2-microglobulin level, loss of antibodies to
      gp41 and p64, or immunoglobulin A level. We have found that our data differ from
      those obtained in studies in homosexual men in the different prognostic value of
      those predictive markers. Our findings should help to identify high risk of
      progression to clinical AIDS among IVDUs, thereby assisting in the selection of
      patients for prophylaxis and therapy.

PMID- 1979744
TI  - Factors influencing outcome of treatment with zidovudine of patients with AIDS in
      Australia. The Australian Zidovudine Study Group.
AB  - In a multicentre study of zidovudine therapy in Australia commencing in June
      1987, 308 homosexual or bisexual men with AIDS started on zidovudine by 30 June
      1988. Using follow-up data collected through 31 December 1988, the outcome of the
      first 18 months of zidovudine therapy in these patients has been analysed in
      terms of efficacy, expressed as survival and as time to development of a new AIDS
      defining condition, and in terms of safety, expressed as toxicity. Median
      survival from time of diagnosis of AIDS was 124 weeks, significantly longer (P
      less than 0.001, logrank statistic) than the median survival of 44 weeks in
      historical controls representing AIDS patients prior to the availability of
      zidovudine therapy. Median survival time from starting zidovudine has not been
      reached in these patients, while 172 (56%) developed new AIDS-defining
      conditions, with median time to progression of 48 weeks. Anaemia requiring
      transfusion was experienced by 155 patients (50%). Significant differences (P
      less than 0.01, logrank statistic) in survival were found in favour of patients
      who commenced zidovudine therapy (Dx-zidovudine time) within 12 weeks of
      diagnosis and had baseline Karnofsky scores greater than or equal to 80,
      haemoglobin greater than or equal to 11 g/dl, CD4+ cell counts greater than or
      equal to 50 x 10(6)/l. Therapy-related significant differences (P less than 0.01,
      logrank statistic) in survival were found in favour of patients with no weight
      loss and who received the full zidovudine dose (1.2g) during the first 52 weeks
      of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1979746
TI  - Syncytium induction by fresh HIV isolates: quantitative analysis using a
      transactivation beta-gal assay.
AB  - We used a quantitative bioassay (the beta-gal assay) to visualize and quantify
      syncytium induction by fresh HIV isolates. This bioassay is based on the
      transactivation by tat of a chimeric gene comprising an HIV-1 long terminal
      repeat (LTR) fused to a modified lacZ gene of Escherichia coli. The chimeric gene
      encodes a beta-galactosidase which is translocated to the nucleus. It allows the
      enzymatic staining of all nuclei from HIV-induced syncytia. Using this
      unequivocal assay (the beta-gal assay), we could assess the syncytium-inducing
      properties of fresh HIV isolates after only 4 days of coculture of patient
      lymphocytes with activated normal lymphocytes. Syncytium-inducing HIV isolates
      were detected in 11 out of 40 seropositive patients studied. They were isolated
      mainly from AIDS patients: eight out of 17 grade IV (according to Centers for
      Disease Control criteria) patients were infected with syncytium-inducing strains.
      However, of 23 grade II and III patients tested, syncytium-inducing HIV strains
      were isolated from three cases. These three patients displayed no detectable p24
      antigenaemia and had a CD4+ cell count of greater than 300 cells/microliter. The
      in vitro replication rate of HIV grown from 36 patient blood samples was then
      examined by sequential p24 antigen measurements in coculture supernatants. The 10
      samples leading to syncytium formation also exhibited the highest replication
      rate. The possibility of unequivocally detecting syncytium-inducing strains after
      only a few days of coculture will make this detection routine and rapid. In
      addition, the limited period of amplification required is a significant advantage
      as it minimizes the emergence of HIV variants selected during long-term in vitro
      cultures.

PMID- 1979745
TI  - Infection of cynomolgus monkeys with HIV-2 protects against pathogenic
      consequences of a subsequent simian immunodeficiency virus infection.
AB  - Simian immunodeficiency virus (SIV) infection in cynomolgus macaques leads to
      severe immunodeficiency with a fatal outcome. In contrast, HIV-2 infects these
      primates without apparently causing any immunological abnormalities. In this
      study three cynomolgus monkeys were experimentally infected with HIV-2 strain SBL
      K135 and 168 days later challenged with 10-100 animal infectious doses of the
      closely related SIV strain SM to study protective immunity. At the time of SIV
      challenge the HIV-2-infected monkeys had neutralizing antibodies against HIV-2,
      but virus could no longer be recovered from their peripheral blood mononuclear
      cells (PBMCs) and no clinical symptoms or decrease in CD4+ lymphocytes were
      observed. Follow-up for 9 months after challenge with SIV showed that the HIV-2
      infected monkeys were protected against SIV-induced immunodeficiency (no decrease
      of CD4+ lymphocytes) and lymphadenopathy. However, they were not resistant to SIV
      infection since virus could be recovered from their PBMCs and they developed
      anamnestic antibody responses. Four naive control monkeys which were inoculated
      with the same dose of SIV became persistently infected and developed a decrease
      of the absolute numbers of CD4+ cells and showed a marked lymphadenopathy. Two
      out of four control animals died 58-265 days postinfection with an
      immunosuppressive disease. Immunohistochemical examination showed abundant viral
      antigen in lymph-node biopsies from the SIV-infected control monkeys but absence
      of SIV or HIV-2 antigens in the biopsies from the three HIV-2-preinfected and SIV
      superinfected monkeys. The present study demonstrates possibilities for induction
      of immunity against immunodeficiency induced by a primate lentivirus, a concept
      with application also to HIV infection and AIDS in man.

PMID- 1979748
TI  - Neu (C-erbB-2) oncogene in breast cancer and its possible association with the
      risk of distant metastases. A retrospective study and review of literature.
AB  - By immunohistochemical staining C-erbB-2 (neu) oncogene was found on the cell
      membrane in 19 out of 44 primary breast cancers from a pathology archive. No
      obvious relation was found between neu oncogene, age, and lymph node status and
      tumor size. There was a tendency towards smaller primary tumors and more estrogen
      receptor-negative tumors in the oncogene-positive group. No case of distant
      metastasis during follow-up was found among the oncogene-negative patients, while
      6 oncogene-positive patients developed such metastases. This suggests that the
      neu oncogene is an independent prognostic factor, which might predict the
      development of distant metastasis. Further studies including more patients and
      long-term survival analysis are, however, needed in order to evaluate the
      prognostic significance of the neu oncogene.

PMID- 1979747
TI  - [Pharmacotherapy of the spino-cerebellar syndromes].

PMID- 1979749
TI  - Electron microscopy and image analysis reveal common principles of organization
      in two large protein complexes: groEL-type proteins and proteasomes.
AB  - In an attempt to settle the question of whether the multicatalytic proteinase or
      proteasome exist in all three kingdoms of life--eukaryotes, archaebacteria, and
      eubacteria--we have undertaken a search for them in the eubacterium Comamonas
      acidovorans. We have, in fact, isolated and purified a cylinder-shaped particle.
      However, according to various structural and biochemical criteria this turned out
      to be more reminiscent of the groEL protein from Escherichia coli and its
      homologs than to proteasomes of eukaryotic or archaebacterial origin. N-terminal
      sequencing provided definite proof for its belonging to this family of molecular
      chaperonins. Image analysis of electron micrographs revealed that the C.
      acidovorans groEL-like protein and proteasomes in spite of their significantly
      different dimensions have certain principles of organization in common.

PMID- 1979750
TI  - Joint IUMS/ICFMH and UNESCO consultation on postgraduate teaching in advanced
      food microbiology with recommendation of a core curriculum.

PMID- 1979751
TI  - Opioid needs of terminal care patients: variations with age and primary site.
AB  - The records of 1383, terminal cancer patients have been reviewed to determine
      whether opioid requirements vary in a consistent pattern with age and with site
      of primary cancer. Opioid requirements are shown to decrease with age in a
      regular pattern and from early adult life. Opioid requirements also differ
      significantly with site of primary cancer and there appears to be a discernible
      pattern of opioid need for different cancers. Patients with sexually related
      cancer have the highest opioid requirements, irrespective of sex. When the
      sexually determined cancers are excluded, the analgesic needs of men and women
      are not significantly different (P = 0.191).

PMID- 1979752
TI  - Use of the polymerase chain reaction in the quantitation of mdr-1 gene
      expression.
AB  - The ability of the polymerase chain reaction (PCR) to quantitate expression of
      mRNA was examined in the present study. The model chosen was expression of the
      multidrug resistance gene mdr-1/Pgp in two colon carcinoma cell lines which
      express mdr-1/Pgp at levels comparable to those found in many clinical samples.
      PCR was utilized to evaluate differences in mdr-1/Pgp expression in the two cell
      lines after modulation by sodium butyrate. Thus, comparisons were made across a
      range of mdr-1/Pgp expression as well as comparisons of small differences. The
      PCR was found to be both sensitive and quantitative. Accurate quantitation
      requires demonstration of an exponential range which varies among samples. The
      exponential range can be determined by carrying out the PCR for a fixed number of
      cycles on serial dilutions of the RNA reverse transcription product, or by
      performing the reaction with a varying number of cycles on a fixed quantity of
      cDNA. By quantitation of the difference in PCR product derived from a given
      amount of RNA from the sodium butyrate treated and untreated cells, the
      difference in mRNA expression between samples can be determined. Normalization of
      the results can be achieved by independent amplification of a control gene, such
      as beta 2-microglobulin, when the latter is also evaluated in the exponential
      range. Simultaneous amplification of the control and target genes results in
      lower levels of PCR products due to competition, which varies from sample to
      sample. The PCR is thus a labor-intensive but sensitive method of quantitating
      gene expression in small samples of RNA.

PMID- 1979754
TI  - Seventh International Congress of Biorheology, Part I. Dedicated to Richard
      Skalak. Nancy, France, 18-23 June 1989. Proceedings.

PMID- 1979753
TI  - Development of the Na(+)-dependent hexose carrier in LLC-PK1 cells is dependent
      on microtubules.
AB  - The Na(+)-dependent hexose carrier, an endogenous apical marker, develops during
      differentiation of LLC-PK1, an established cell line with characteristics of the
      proximal tubule. This development was inhibited by the microtubule-disrupting
      drugs, colchicine and nocodazole, while it was insensitive to lumicolchicine.
      This strongly suggests that microtubules are involved in the plasma membrane
      expression of the Na(+)-dependent hexose carrier. We also analyzed the increase
      in activity of endogenous apical and basolateral membrane proteins during the
      polarization process. The development of three apical (Na(+)-dependent hexose
      carrier, gamma-glutamyltransferase and alkaline phosphatase) and one basolateral
      membrane protein (Na+/K(+)-ATPase) was studied during the reorganization of LLC
      PK1 cells into a polarized epithelium. Colchicine inhibited the rapid, transient
      increase in the expression of the Na(+)-dependent hexose carrier during this
      polarization process. A similar result was observed for the development of the
      other apical proteins, while the development of Na+/K(+)-ATPase seemed to be
      largely insensitive to colchicine. Our results are in agreement with the model
      that the vesicles containing the apical membrane proteins use microtubules as
      tracks to reach the plasma membrane. The transport of vesicles containing
      basolateral membrane proteins clearly occurs by a different pathway which is
      independent on an intact microtubular network. Since the inhibition by the
      microtubule-disrupting drugs was complete, it can be concluded that after
      disruption of microtubules, the apical vesicles do not use the basolateral
      pathway by default.

PMID- 1979755
TI  - First line treatment in hypertension.

PMID- 1979756
TI  - Modeling and closed-loop pharmacologic control of the ventricular rate during
      induced atrial fibrillation in anesthetized dogs.
AB  - An automated drug delivery system that provides closed-loop feedback control of
      the ventricular rate during atrial fibrillation is described. The control system
      was designed using a mathematical model of the effect of esmolol infusion in the
      ventricular rate. The model was developed in system identification experiments
      with anesthetized dogs in which atrial fibrillation was induced and maintained by
      rapid atrial pacing. A control system of variable structure, which incorporates a
      transient controller and a regulator, was designed to perform satisfactorily over
      a wide range of subject responses to drug infusion. The transient controller
      brings the ventricular rate to the setpoint with little overshoot. When the
      ventricular rate is near the setpoint, the drug infusion rate is calculated by
      the regulator. The drug infusion rate is constrained to ensure smooth transitions
      in the hemodynamic state of the patient and for safety. Feasibility of the system
      was demonstrated in computer simulations and animal experiments.

PMID- 1979757
TI  - Distinctive chromosomal structures are formed very early in the amplification of
      CAD genes in Syrian hamster cells.
AB  - As visualized by in situ hybridization with fluorescence detection, newly
      amplified CAD genes in 10(5) cell colonies are contained in multiple copies of
      very large regions of DNA, each tens of megabases long. The extra DNA is usually
      linked to the short arm of chromosome B9, which retains CAD at its normal site.
      The widely spaced genes are often interspersed with new G-negative regions.
      Individual cells within a clone have highly variable numbers of CAD genes (range
      2-15). When resistant clones are examined later, at the 10(15) cell stage, the
      amplified genes are usually found in much more condensed structures. We propose
      that, in the initial event of CAD gene amplification, much of the short arm is
      transferred from one B9 chromosome to another. In subsequent cell cycles this
      initial duplication expands rapidly through unequal but homologous sister
      chromatid exchanges. Relatively rare secondary events lead to more condensed
      structures.

PMID- 1979758
TI  - The viral erbA oncogene protein, a constitutive repressor in animal cells, is a
      hormone-regulated activator in yeast.
AB  - The v-erbA oncogene is a retrovirus-transduced and altered copy of a cellular
      gene for a thyroid hormone receptor. In animal cells, the v-erbA protein fails to
      respond to hormone and acts as a dominant negative allele, inhibiting gene
      activation normally conferred by the wild-type thyroid hormone receptor. We
      report here that, unexpectedly, the v-erbA protein acts as a hormone-regulated
      transcriptional activator in S. cerevisiae. We suggest that the ability of v-erbA
      protein to function as a transcriptional repressor or an activator is determined
      by interaction with, or modification by, other cellular factors, and that this
      phenomenon may be relevant to understanding ligand regulation of the normal
      thyroid and steroid hormone receptors.

PMID- 1979759
TI  - Effect of dietary alpha-linolenic acid on equine monocyte procoagulant activity
      and eicosanoid synthesis.
AB  - To investigate the effects of an omega-3 fatty acid-enriched ration on the in
      vitro response of equine monocytes to endotoxin, an 8-week feeding trial was
      conducted in which linseed oil served as the source of the omega-3 fatty acid,
      alpha-linolenic acid. One group of horses was fed a control pelleted ration and
      the other group was fed an 8% linseed oil-enriched pelleted ration. After 8 weeks
      of feeding, monocytes were isolated and incubated in the presence of Escherichia
      coli O55:B5 endotoxin for 6 hr. After 8 weeks on the rations, the mean
      procoagulant activity and thromboxane B2 production by endotoxin-stimulated
      monocytes from horses consuming the linseed oil ration decreased by 51% and 71%,
      respectively, compared with cells from horses consuming the control ration. There
      was no difference in monocyte synthesis of 12-hydroxyeicosatetraenoic acid or
      leukotriene B4 between groups. Fatty acid analysis of membrane phospholipids
      revealed a decrease in the omega-6:omega-3 ratio in monocytes from horses
      consuming the linseed oil ration. These data suggest that dietary supplementation
      with alpha-linolenic acid may modify the response to endotoxin by reducing the
      synthesis of potentially harmful cellular mediators.

PMID- 1979761
TI  - Comparative biochemical and immunological studies on gamma-glutamyltransferases
      from human kidney and renal cell carcinoma applying monoclonal antibodies.
AB  - We have purified gamma-glutamyltransferases (GGT) from human kidneys and renal
      cell carcinomas, and fractionated them according to different lectin-binding
      properties of the isoenzymes. Native polyacrylamide gel electrophoresis and
      isoelectric focusing revealed different GGT-bands (even after desialylation) not
      only among kidney and renal carcinoma, but also among Con A-affine tumor
      fractions separated by ion-exchange chromatography. Mr of native GGTs were
      between 106 to 161 kDa, the pI ranged from pH 3 to 4 (pH 5 to 6 after
      desialylation). Monoclonal antibodies to GGT were produced. One of these, of IgG1
      class and designed 138H11, recognizes human kidney GGT and, in addition, GGT from
      renal cell carcinomas and liver carcinomas. The specificity of mAb 138H11 for GGT
      was confirmed by Western blotting, by immunohistochemistry and by
      immunoprecipitation. The potential usefulness of mAb 138H11 in monitoring renal
      cancer patients and in identification of renal cancer metastases is currently
      being studied.

PMID- 1979760
TI  - Neuronal plasticity in the developing chick brain: interaction of ethanol and
      neuropeptides.
AB  - We have examined the influence of ethanol on cholinergic and catecholaminergic
      neuronal expression in the chick embryonic brain using choline acetyltransferase
      (ChAT) and tyrosine hydroxylase (TH) activities as respective neuronal markers.
      Ethanol (5-20 mg/50 microliters/day), administered to embryos in ovo from day 1
      to 3 of development produced a dose-dependent decrease in ChAT activity while TH
      activity exhibited a dose-dependent increase when embryos were sacrificed on
      embryonic day 8. The optimal neurotoxic dose of ethanol following this paradigm
      was 15 mg/day and the LD50 was 17.5 mg/day for the 3 days. Subsequently, embryos
      were administered ethanol (15 mg) either alone or concomitantly with growth
      hormone-releasing hormone (GH-RH; 100 ng/50 microliters/day). Previous studies
      from this laboratory have demonstrated both potent cholinotropic and
      catecholaminotropic effects for this neuropeptide, results confirmed in this
      study. Co-administration of ethanol and GH-RH resulted in a significant increase
      in ChAT activity as compared to both saline- and ethanol-treated controls when
      examined on day 8 of embryonic growth. No additive effect was observed in TH
      activity following co-administration of ethanol and GH-RH. The findings from this
      study are interpreted to mean that GH-RH represents a potent secondary signal to
      undifferentiated neuroblasts which may lead to a restoration of the cholinergic
      neuronal population following neurotoxic insult by ethanol.

PMID- 1979762
TI  - Gamma-glutamyltransferase from human hepatoma cell lines: purification and cell
      culture of HepG2 on microcarriers.
AB  - After screening different human hepatoma cell lines, we observed that both HepG2
      and PLC/PRF/5 naturally produced large amounts of gamma-glutamyltransferase. We
      optimized HepG2 cell culture conditions and observed that higher cell densities
      were obtained when cells were cultured on microcarriers, particularly when
      Cytodex 3 was used and that cell growth was optimal when DMEM, the basic medium,
      was supplemented with 5% fetal calf serum and 6 mmol/l glutamine. These culture
      conditions allowed us to produce the highest amounts of GGT after about 150 h of
      culture. The GGT obtained from HepG2 cells was partially purified and some of its
      physico-chemical properties characterized. Successive Con A gel chromatography
      separated the activity into two peaks, suggesting that GGT from HepG2 is not
      uniformly glycosylated. Papain-treated HepG2 GGT showed a Mr of about 120 kDa and
      migrated as a single-chain protein in SDS-PAGE. Immunological and kinetic
      properties of the GGT were similar to other human GGTs (liver, kidney and serum).
      It appears that HepG2 GGT could be a source for the preparation of a human enzyme
      reference material.

PMID- 1979763
TI  - A comparative study on the hormonal responses to insulin-induced hypoglycaemia
      using semisynthetic human insulin and pork insulin in patients with type 1
      diabetes mellitus.
AB  - In order to enlighten the controversy on whether human and pork insulin result in
      different hormonal responses to insulin-induced hypoglycaemia, eight C-peptide
      negative, diabetic patients without measurable circulating insulin-binding
      antibodies were exposed to insulin-induced hypoglycaemia in random order with
      highly purified pork insulin (Actrapid) and semisynthetic human insulin (Actrapid
      Human). Hypoglycaemia was provoked by a constant rate IV infusion of insulin
      (0.034 U kg-1 h-1) for 3 h after which the blood glucose recovery was assessed
      for an additional period of 60 min. Both insulin preparations gave close to
      identical responses for glucose, glucagon, growth hormone, adrenaline, and
      somatostatin. The circulating noradrenaline levels were higher during the
      infusion of pork insulin which also yielded a more prominent response of
      pancreatic polypeptide and, after cessation of the insulin infusion, plasma
      cortisol was also higher following pork insulin. It is concluded that human and
      pork insulin induce close to identical responses of the important counter
      regulatory hormones during hypoglycaemia in Type 1 diabetic patients.

PMID- 1979764
TI  - The neurophysiological regulation of growth hormone secretion.
AB  - With the advent of genetic engineering, the importance of GH in the regulation of
      growth and metabolism in domestic species has been clearly demonstrated. Ample
      evidence of an integral role for GH in the processes of growth and lactation
      exists in dairy cattle (1,2), sheep (3), beef cattle (4) and swine (5). For
      example, circulating GH levels are high during the period of rapid growth in
      several species including cattle (6), swine (7) and poultry (8). Endogenous GH
      secretion is primarily controlled by the central nervous system (CNS) via two
      specific hypothalamic neurohormones, growth hormone-releasing factor (GRF) and
      somatostatin (SRIF), an inhibitor of GH release. The secretion of GRF and SRIF is
      governed by a host of neuropeptides and neurotransmitters which provide a
      functional link between higher CNS centers and hypophysiotropic neurons. This
      review will focus on the CNS regulation of GH secretion and circulating factors
      which feedback to either stimulate or inhibit its release.

PMID- 1979765
TI  - The effects of beta agonists on muscle cells in culture.
AB  - Increases in protein synthesis of 12% were found with two myogenic cell lines (L6
      and G8-1) on treatment for 6 hr with the beta-adrenergic agonist cimaterol. In L6
      cells, propranolol blocked the effect. Protein breakdown measured over 18-24 hr
      was unchanged. The Kd for cimaterol binding to the L6 beta-receptor was 26 nM
      which was compatible with its EC50 for the stimulation of protein synthesis
      (approx 5 nM). Evidence provided with muscle cell lines indicates a direct effect
      of cimaterol on protein synthesis, which may contribute to muscle accretion in
      cimaterol-fed animals.

PMID- 1979766
TI  - Plasma and tissue concentrations and molecular forms of somatostatin in calves
      infected with Sarcocystis cruzi.
AB  - The effects of parasitic infection on plasma and tissue content of immunoreactive
      somatostatin (SRIF) were studied in 4-mo old male calves inoculated with the
      protozoan Sarcocystis cruzi. Because feed intake significantly decreased (70%) in
      infected calves around day 28 postinfection (pi), concomitant with the asexual
      replication of S. cruzi and outward expression of clinical signs, the relative
      contributions of infection and associated reduction in nutrition on plasma SRIF
      were evaluated. Treatment groups were: noninfected ad libitum fed (C), infected
      (250,000 S. cruzi oocysts per os) ad libitum fed (I) and noninfected calves
      pairfed to the level of intake of each infected calf (PF). Mean plasma
      concentrations of SRIF (pg/ml) on day 30 pi were: C, 224 +/- 22; I, 742 +/- 150;
      PF, 246 +/- 31 (effect of infection P less than .05). In another study, SRIF was
      measured in plasma and in pancreatic, duodenal, jejunal and ileal tissue extracts
      from normal and S. cruzi infected calves. Plasma and tissue samples were
      collected on day 42 pi. Mean plasma SRIF were 2.5 times higher in infected than
      control calves. Plasma insulin and insulin-like growth factor 1 was lower in
      infected v control calves (P less than .02). Plasma glucagon was similar between
      groups. Duodenal (P less than .05) and jejunal (P less than .02) SRIF content was
      higher in infected than control calves. Chromatography of tissue extracts on
      Sephadex G-50 revealed that the increase in SRIF was accounted for, in part, by
      molecular forms larger than cyclic SRIF-14. Data suggest that peripheral SRIF is
      increased in calves during S. cruzi infection. The increase in SRIF is not solely
      related to plane of nutrition. Altered levels of gut SRIF(s) may be associated
      with perturbed metabolic regulation in parasitized animals through direct effects
      on the gut.

PMID- 1979767
TI  - Evolution and trends in peritoneal dialysis. An international meeting. October 27
      28, 1989. Proceedings.

PMID- 1979769
TI  - Genetics of NIDDM.
AB  - This brief review discusses the current level of understanding of the role of
      genetic defects in the etiology of non-insulin-dependent diabetes mellitus
      (NIDDM) and the use of molecular-genetic methods for this study. Evidence for
      genetic susceptibility is strong, and defects in both insulin production and
      action are suspect. With restriction-fragment-length polymorphisms and genomic
      sequencing, various candidate loci are being evaluated. Evidence that multiple
      genes are involved is only circumstantial. If NIDDM is genetically heterogeneous
      and also influenced by environmental components, population associations and
      linkage analyses in families may not be as easily interpreted as for diseases
      involving single major gene defects.

PMID- 1979768
TI  - [The natural infection rate of mosquitoes by Japanese encephalitis B virus in
      Yunnan Province].
AB  - In July-September 1983-1987, 57,898 adult female mosquitoes belonging to 29
      species of 8 genera were collected from Japanese B encephalitis (JE) epidemic
      areas in Yunnan, China, and were examined by C 6/36 cell method and sucking mouse
      method. Twenty-eight strains of JE virus were isolated from Culex
      tritaeniorhychus, C. whitomorei, C. pseudovishnui, C. fuscocephala, C. annulus,
      C. gelidus, Anopheles sinensis, Mansonia uniformis, Aedes albopictus, Ae. Vexans,
      Ae. lineatopennis, and Ae. assamensis. The positive isolation rates by the two
      methods were 6.19% and 3.33% respectively. The highest positive isolation rate
      12.3% (per 100 pools), moiquito body virus carrier rate 1:208 or moiquito body
      virus carrier rate 4.81% (per 1000 mosquitoes) were found in the middle ten days
      of August, corresponding to epidemic peak of JBE Nine strains of JE virus were
      isolated from C tritaeniorhychus with an isolation rate of 7.44%, natural
      isolation ratio was 1.584 and mosquito body virus carrier rate 1.71%. These
      results indicated that C. tritaeniorhynchus might be the main vector of JE virus
      in Yunnan, while C. whitmorei, C. pseudovishnui and An. sinensis are also
      important vectors of JE virus in Yunnan.

PMID- 1979770
TI  - [Selection criteria for differential therapy with beta receptor blockers].

PMID- 1979771
TI  - The status of periodontal health and oral hygiene of Miraa (catha edulis)
      chewers.
AB  - Two hundred and thirty one miraa chewers and 199 non miraa chewers were assessed
      for gingivitis, loss of attachment and oral hygiene status. The mean gingivitis
      score among miraa chewers was 1.6 and 1.7 among non miraa chewers (P less than
      0.05). The mean facial gingivitis score among miraa chewers was 1.5 and 1.6 among
      non miraa chewers (P greater than 0.05). The mean distal gingivitis score among
      miraa chewers was 1.5 and 1.7 among non miraa chewers (P less than 0.05). The
      mean lingual gingivitis score among miraa chewers was lower than that of non
      miraa chewers (P less than 0.05). The means of loss of attachment of the teeth of
      miraa chewers were equal to those of non miraa chewers. Although the mean surface
      plaque scores of miraa chewers were generally lower than those of non miraa
      chewers, only the mean lingual plaque score of miraa chewers was found to be
      significantly lower than that of non miraa chewers (P less than 0.05). It is
      concluded that the oral hygiene status of miraa chewers was generally better than
      that of non miraa chewers and there was no evidence to show that chewing miraa is
      detrimental to periodontal health.

PMID- 1979772
TI  - Effect of glucocorticoids on alkaline phosphatase, alanine aminotransferase, and
      gamma-glutamyltransferase in cultured dog hepatocytes.
AB  - Glucocorticoid(GC)-induced hepatopathy in the dog is characterized by abnormal
      liver morphology and increases in serum alanine aminotransferase (ALT), gamma
      glutamyltransferase (GGT), and the liver alkaline phosphatase isoenzyme (LALP)
      and by the appearance of an unusual isoenzyme of alkaline phosphatase known as
      the corticosteroid-induced alkaline phosphatase isoenzyme (CALP). It has not been
      shown whether the increases in serum ALT, GGT, and LALP are as a result of an
      increase in production of these enzymes or as a result of the GC-induced
      hepatocellular swelling and possible membrane alterations. Also, it has been
      assumed that the mechanism of production of CALP is via GC-induced gene
      derepression and de novo protein synthesis; however, this hypothesis has not been
      directly tested. Using isolated dog hepatocytes maintained in a confluent
      monolayer culture in the presence and absence of GC or cyclic AMP, no statistical
      increase in serum ALT, GGT, or LALP was observed. A combination of GC and cyclic
      AMP also caused no statistical increase in ALT and GGT; however, we demonstrate
      that these conditions clearly stimulated the de novo synthesis of LALP. These
      conditions do not induce the synthesis of CALP as determined by a sensitive
      immunoassay. The data obtained using this in vitro model suggest that the primary
      mechanism(s) of the in vivo increase of serum ALT and GGT in GC treated dogs may
      be other than that of de novo protein synthesis. Likewise, in vitro production of
      CALP may be a mechanism more complex than the conditions tested in this study.

PMID- 1979773
TI  - Changing concepts in the management of hereditary and sporadic medullary thyroid
      carcinoma.
AB  - Recent linkage of the gene for multiple endocrine neoplasia type 2A and 2B to the
      centromeric region of chromosome 10 has provided new insight into the causes of
      medullary thyroid carcinoma and has provided tools to diagnose gene carriers
      status for this syndrome with greater than 90% certainty. This review focuses on
      how these advances influence the clinical management of both sporadic and
      hereditary medullary thyroid carcinoma and discusses how tests based on the
      genetic linkage studies will aid in the early diagnosis and treatment of this
      syndrome. In addition, the authors have focused on several controversial
      management questions regarding the type and extent of surgery for this thyroid
      tumor, the management of the patient with metastatic disease, and the approach to
      management of other manifestations of multiple endocrine neoplasia types 2A and
      2B. This review attempts to provide a balanced overview of these complex issues.

PMID- 1979774
TI  - International Symposium on Nutritional Toxicology and Food Safety. 11-13 April
      1989, Toulouse, France. Proceedings.

PMID- 1979775
TI  - Intestinal and pancreatic adaptation. Adaptational response and repair mechanisms
      in the enter-pancreatic system. Proceedings of the 4th International Conference,
      Berlin, October 25-28, 1989.

PMID- 1979776
TI  - Effect of massive small bowel resection on components of the peptidergic
      innervation of the rat small intestine.
AB  - The effect of massive small bowel resection on the immunostaining of
      neuropeptides in the submucous plexus of the retained small intestine was
      examined. The neuropeptides chosen were somatostatin and vasoactive intestinal
      polypeptide because these are markers for two of the major populations of neurons
      in the plexus. Three different methods were used to assess the effect of
      resection on the enteric nervous system. Firstly immunocytochemical staining of
      neuropeptide containing neurons and nerve fibers was compared between test and
      control animals. The results demonstrated a significant increase in the number
      and size of the vasoactive intestinal polypeptide containing neurons with no
      change in the number of somatostatin neurons although these were also increased
      in size. Secondly the possibility that the increase in neuron number might be the
      result of neuronal division was examined by 3H-thymidine incorporation
      experiments. The results demonstrated that no neuronal elements were labelled.
      Finally the possibility that the increase in vasoactive intestinal peptide was
      the result of an increase in transcription was assessed by Northern blot
      analysis. The results demonstrated a small but significant increase in mRNA
      levels. It was concluded that massive small bowel resection directly affects
      neuropeptide levels in the submucous plexus, resulting in an increase in
      vasoactive intestinal polypeptide-immunoreactive neurons.

PMID- 1979778
TI  - A landmark for home care in Canada.

PMID- 1979777
TI  - VIP receptors in human SUP-T1 lymphoblasts.
AB  - We characterized a new type of vasoactive intestinal peptide (VIP) receptors in
      the CD4+ Stanford University Pediatric (SUP)-T1 lymphoma cell line, by comparing
      receptor occupancy [in the presence of (125I)helodermin and (125I)(acetyl
      His1)VIP] and adenylate cyclase activation (in the presence of GTP). The order of
      potency of peptides on both parameters was: helodermin greater than (acetyl
      His1)VIP greater than (Phe1)VIP = VIP greater than PHI while secretin was
      ineffective. In membranes, when Gs was permanently activated by Gpp(NH)p or by
      ADP-ribosylation (after pretreating intact lymphoblasts for 2 h with cholera
      toxin), there resulted a variably increased affinity of receptors for VIP-like
      peptides, suggesting reduced receptor selectivity. Preexposing intact
      lymphoblasts to the same peptides induced, within 5 min, homologous
      desensitization (i.e. reduced binding capacity and even more so impaired
      capability to activate adenylate cyclase), whose extent correlated with the Kd of
      each peptide at time 0. After prolonged (16 h) exposure to 30 nM VIP that
      resulted in marked (75%) downregulation, 60% of the adenylate cyclase
      responsiveness could recover within 30-120 min even in the presence of
      cycloheximide, but further resensitization was cycloheximide-sensitive. To
      conclude, VIP receptors coupled to adenylate cyclase showed distinct specificity
      in human SUP-T1 lymphoblasts. Their specificity decreased when Gs was permanently
      activated. In intact cells exposed to VIP-like peptides, the receptors were
      rapidly desensitized, then down-regulated, the resensitization mechanism being
      not immediately inhibited by cycloheximide.

PMID- 1979779
TI  - VIIIth International Symposium on Radioimmunology. Lyon, France, 25-27 April
      1990. Proceedings.

PMID- 1979780
TI  - A novel endothelial cell growth factor circulates in familial multiple endocrine
      neoplasia type 1.

PMID- 1979781
TI  - Expression patterns of mRNAs for ammonia-metabolizing enzymes in the developing
      rat: the ontogenesis of hepatocyte heterogeneity.
AB  - The expression patterns of the mRNAs for the ammonia-metabolizing enzymes
      carbamoylphosphate synthetase (CPS), glutamine synthetase (GS) and glutamate
      dehydrogenase (GDH) were studied in developing pre- and neonatal rat liver by in
      situ hybridization. In the period of 11 to 14 embryonic days (ED) the
      concentrations of GS and GDH mRNA increases rapidly in the liver, whereas a
      substantial rise of CPS mRNA in the liver does not occur until ED 18. Hepatocyte
      heterogeneity related to the vascular architecture can first be observed at ED 18
      for GS mRNA, at ED 20 for GDH mRNA and three days after birth for CPS mRNA. The
      adult phenotype is gradually established during the second neonatal week, i.e. GS
      mRNA becomes confined to a pericentral compartment of one to two hepatocytes
      thickness, CPS mRNA to a large periportal compartment being no longer expressed
      in the pericentral compartment and GDH mRNA is expressed over the entire porto
      central distance, decreasing in concentration going from central to portal.
      Comparison of the observed mRNA distribution patterns in the perinatal liver,
      with published data on the distribution of the respective proteins, points to the
      occurrence of posttranslational, in addition to pretranslational control
      mechanisms in the period of ontogenesis of hepatocyte heterogeneity.
      Interestingly, during development all three mRNAS are expressed outside the liver
      to a considerable extent and in a highly specific way, indicating that several
      organs are involved in the developmentally regulated expression of the mRNAs for
      the ammonia-metabolizing enzymes, that were hitherto not recognized as such.

PMID- 1979782
TI  - Evidence for particulate guanylate cyclase in rat kidney after stimulation by
      atrial natriuretic factor. An ultracytochemical study.
AB  - Cytochemical localization of particulate guanylate cyclase (GC) in rat kidney,
      after stimulation with atrial natriuretic factor (ANF), was studied by electron
      microscopy. In the renal corpuscle GC reaction was localized on podocytes. Other
      segments of the nephron that showed ultracytochemical evidence of GC activity
      were the proximal convoluted tubule, the thick ascending limb of the loop of
      Henle and the collecting tubule. All GC positivity was associated with plasma
      membranes. Samples incubated in basal conditions (without ANF) did not reveal any
      GC reaction product. These results indicate that ANF is a strong activator of
      particulate GC. Our data also suggests that, through the enzyme, ANF acts
      directly on epithelial cells of tubules where Na+ reabsorption occurs. This is in
      agreement with the hypothesis that ANF has a direct tubular effect on
      natriuresis.

PMID- 1979783
TI  - The effect of various levels of ractopamine hydrochloride on the performance and
      carcass characteristics of finishing swine.
AB  - Six trials involving 888 pigs (Study 1) and three trials involving 360 pigs
      (Study 2) were conducted at various geographical locations in the U.S. and Canada
      to evaluate the effect of ractopamine hydrochloride on the performance and
      carcass characteristics of finishing swine. All trials were conducted using a
      randomized complete block design. Trial data were pooled within study for
      statistical analysis. Pigs averaged approximately 64.5 kg (Study 1) and 65.9 kg
      (Study 2) initially and had ad libitum access to a 16% crude protein corn-soybean
      meal or barley-soybean meal diet. Ractopamine was included in the diet at 0, 2.5,
      5, 10, 20 or 30 ppm (Study 1), or at 0, 5, 10, 15 or 20 ppm (Study 2); diets were
      fed for an average of 45 d (Study 1) and 50 d (Study 2) to a final weight of
      about 104.3 kg (Study 1) and 106.6 kg (Study 2). Carcass dissection data were
      collected in three of the six trials in Study 1 (0, 5 and 20 ppm ractopamine) and
      in all three trials in Study 2 (0, 5, 10, 15 and 20 ppm ractopamine). All
      ractopamine levels improved (P less than .05) ADG and feed: gain (Studies 1 and
      2) above those of control pigs. Ractopamine levels of 10 to 30 ppm (Studies 1 and
      2) improved (P less than .05) dressing percentage over controls. Pigs fed
      ractopamine at 5 and 20 ppm (Study 1) and 10, 15 and 20 ppm (Study 2) had
      increased (P less than .05) dissected leanness compared with controls.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1979784
TI  - Manipulation of porcine carcass composition by ractopamine.
AB  - The effect of dietary ractopamine and protein level on growth performance,
      individual muscle weight and carcass composition of finishing pigs were evaluated
      in two experiments. Twelve barrows and 12 gilts (Exp. 1) and 32 barrows (Exp. 2)
      with an average initial weight of 64 kg were penned individually and offered
      ractopamine at 0 or 20 ppm in diets containing 13 or 17% CP in 2 x 2 factorial
      experiments for 28 d. In both experiments, dietary ractopamine improved daily
      gain (P less than .1) and gain-to-feed ratio (P less than .05) at 17% dietary
      protein level but depressed these response criteria at 13% protein level. Leaf
      fat was reduced (P less than .05) and longissimus muscle depth was increased (P
      less than .1) by feeding ractopamine regardless of dietary CP concentration.
      Longissimus, psoas major, semitendinosus, biceps and quadriceps femoris (P less
      than .05) and tensor facia latae (P less than .1) muscles were 8 to 22% heavier
      with ractopamine feeding at 17% dietary CP level. Results from both trials
      suggest that ractopamine improves growth rate and carcass leanness at the higher
      dietary protein level but improves only carcass leanness at the lower protein
      level.

PMID- 1979785
TI  - Effects of ractopamine on genetically obese and lean pigs.
AB  - Twenty-eight genetically obese and 24 lean barrows (65.0 and 68.7 kg average BW,
      respectively) were allotted within genotype to a 16% CP corn-soybean meal basal
      diet or this basal diet + 20 ppm ractopamine (a phenethanolamine beta-adrenergic
      agonist) and allowed ad libitum access to feed for 48 d. Compared to lean pigs,
      obese pigs had lower ADG, gain to feed ratio, longissimus muscle area, predicted
      amount of muscle, and weights of trimmed loin and ham, ham lean, heart, spleen,
      kidney and gastrointestinal tract (P less than .05). Obese pigs also had shorter
      carcass but higher dressing percentage, backfat thickness, fat depth, fat area,
      untrimmed loin weight and fasting plasma urea N concentration (P less than .05).
      Dietary supplementation with 20 ppm ractopamine reduced daily feed intake and
      improved gain to feed ratio in both lean and obese pigs (P less than .05). Pigs
      fed ractopamine had shorter carcasses, less fat depth and fat area, smaller
      weights of stomach and colon plus rectum, but higher dressing percentages,
      longissimus muscle areas, weights of trimmed Boston butts, picnics and loins, ham
      lean and predicted amounts of muscle than pigs not fed ractopamine (P less than
      .05). Supplemental ractopamine had no effect on fasting plasma concentrations of
      urea N, nonesterified fatty acids, triglyceride or glucose (P greater than .05).
      No genotype x ractopamine interactions for the criteria described above were
      detected (P greater than .05). These results suggest that ractopamine will
      improve the efficiency of feed utilization and carcass leanness in swine with
      different propensities for body fat deposition.

PMID- 1979786
TI  - Reduced sensitivity to beta-adrenergic agonists in Basenji-Greyhound dogs.
AB  - To investigate the inhibitory effects of beta-adrenergic agonists and
      aminophylline on pulmonary responsiveness, we evaluated the ability of albuterol
      and aminophylline to attenuate pulmonary responses to aerosol challenge with
      methacholine and histamine in intact Basenji-Greyhound (BG) and selected mongrel
      dogs. Pulmonary responses were measured in untreated dogs and in dogs pretreated
      with albuterol (1 and 2.5 micrograms/kg) or aminophylline. Before aerosol
      challenge, baseline pulmonary resistance (RL) and dynamic compliance (Cdyn) were
      not significantly different between the BGs and the mongrels. In the untreated
      dogs, pulmonary responses to methacholine and histamine aerosols were not
      different between the BGs and the mongrels. Pretreatment with albuterol (1
      microgram/kg) or aminophylline significantly attenuated the pulmonary response to
      methacholine in the mongrels but was without effect in the BGs. Albuterol (2.5
      micrograms/kg) significantly attenuated the pulmonary response to methacholine in
      the BGs and the mongrels; however, this attenuation was significantly greater (P
      less than 0.05) in the mongrels than in the BGs. In response to histamine
      challenge, no differences were seen between the BGs and the mongrels in the
      control state (no pretreatment) or after pretreatment with albuterol or
      aminophylline. This study demonstrates that in BGs pulmonary responsiveness to
      methacholine but not histamine is resistant to inhibition by beta-adrenergic
      agonists. This may result from a qualitative or quantitative defect in either the
      cholinergic or beta-adrenergic receptor or to an abnormality distal to the
      receptors in the signal transduction mechanism at a site where the two signals
      interact.

PMID- 1979787
TI  - Effect of LY171883 on endotoxin-induced lung injury in pigs.
AB  - We evaluated the role of sulfidopeptide leukotrienes as mediators of endotoxin
      induced respiratory failure in pigs. Escherichia coli endotoxin (055-B5) was
      infused intravenously into anesthetized 10- to 14-wk-old pigs at 5 micrograms/kg
      the 1st h followed by 2 micrograms.kg-1.h-1 for 3 h in the presence and absence
      of LY171883, a specific leukotriene D4 (LTD4)/LTE4 receptor antagonist. Endotoxin
      caused hemoconcentration, granulocytopenia, decreased cardiac index, systemic
      hypotension, pulmonary hypertension, increased pulmonary vascular resistance,
      bronchoconstriction, hypoxemia, increased permeability of the alveolar-capillary
      membrane, pulmonary edema, and increased plasma concentrations of thromboxane B2
      (TxB2), prostaglandin F2 alpha (PGF2 alpha), and 6-keto-PGF1 alpha. LY171883 did
      not modify endotoxin-induced cardiopulmonary and hematologic abnormalities,
      except for a modest attenuation of pulmonary hypertension (at 1 h) and increased
      pulmonary vascular resistance (at 1-2 h). Ex vivo stimulation of whole blood with
      calcium ionophore caused large increases in plasma concentrations of TxB2, PGF2
      alpha, and LTB4. These increases were not significantly modified in blood derived
      from pigs treated with LY171883, indicating no inhibition of cyclooxygenase or 5
      lipoxygenase. We conclude that LTD4 and LTE4 are not important mediators of
      endotoxin-induced lung injury in anesthetized pigs, although they may contribute
      modestly to pulmonary vasoconstriction.

PMID- 1979789
TI  - 15th International Cancer Congress. Hamburg, August 16-22, 1990. Part I: Poster
      abstracts.

PMID- 1979788
TI  - Effect of synchronous increase in intrathoracic pressure on cardiac performance
      during acute endotoxemia.
AB  - In the anesthetized closed-chest canine model of Gram-negative endotoxemia (n =
      10), we tested the hypothesis that the effect of cardiac cycle-specific
      intrathoracic pressure pulses delivered by a heart rate-(HR) synchronized high
      frequency jet ventilator (sync HFJV) on systolic ventricular performance is
      dependent on the level of preload. To control for HFJV frequency, hemodynamic
      responses were also measured at fixed frequency within 15% of HR (async HFJV).
      Biventricular stroke volumes (SV) were measured by electromagnetic flow probes.
      Measurements were made before (baseline) and 30 min after infusion of 1 mg/kg
      Escherichia coli endotoxin (serotype 055:B5) and then after 2 mg/kg propranolol
      at both low (less than 10 mmHg) left ventricular filling pressure (LVFP) and high
      (greater than 10 mmHg) LVFP. Ventricular function curves, aortic pressure-flow (P
      Q) relationships, and venous return (VR) curves were analyzed. We found that
      endotoxin did not alter VR curves but shifted the aortic P-Q curves to the left
      with pressure on the x-axis (P less than 0.05). Volume loading increased SV (P
      less than 0.01) because of a rightward shift of the VR curve. No specific
      differences occurred with either sync or async HFJV during endotoxin, presumably
      because of preserved VR and shifted aortic P-Q. The lack of cardiac cycle
      specific effects of ITP appears to be due to the selective endotoxin-induced
      changes in peripheral vasomotor tone that counterbalance any depressed myocardial
      contractility.

PMID- 1979790
TI  - 15th International Cancer Congress. Hamburg, August 16-22, 1990. Part II: Lecture
      abstracts.

PMID- 1979791
TI  - Separation of the enantiomers of beta-receptor blocking agents and other cationic
      drugs using a CHIRAL-AGP column. Binding properties and characterization of
      immobilized alpha 1-acid glycoprotein.
AB  - The effect of the immobilization procedure on the conformation of alpha 1-acid
      glycoprotein (AGP) was investigated by recording the fluorescence spectra of
      native and immobilized AGP. A 20-nm red shift was obtained for the immobilized
      form of AGP compared with the emission maximum of 338 nm obtained for native AGP.
      This demonstrates that the tryptophan residues are exposed on the protein surface
      after immobilization, indicating that the immobilized form of AGP has a more
      unfolded structure than the native AGP. The effect of N,N-dimethyloctylamine on
      the enantioselectivity for some fentiazine derivatives, observed with immobilized
      AGP, was equal to that obtained with AGP as a chiral complexing agent in the
      mobile phase. This demonstrates that even though the immobilization procedure
      affects the conformation of the protein there still exist large similarities
      between native and immobilized AGP concerning chiral recognition. The adsorption
      isotherm of (-)-terodiline was studied by use of the breakthrough technique. The
      adsorption isotherm indicates that (-)-terodiline is adsorbed to one site with
      high affinity and at least one more site with lower affinity. It was also
      observed that the enantiomers of amines, acids and non-protolytic compounds
      compete with the cationic compound, (-)-terodiline, for binding to the same
      sites. The beta-receptor blocking agents atenolol, metoprolol, pindolol,
      alprenolol, oxprenolol and propranolol were resolved on a CHIRAL-AGP column. The
      retention and enantioselectivity are highly influenced by the structure of the
      solute and the nature of the uncharged mobile phase additives. Separation factors
      of 1.2-1.8 were obtained for the beta-blockers under the studied conditions.

PMID- 1979792
TI  - The dopaminergic amacrine cell.
AB  - The detailed morphology of the dopaminergic amacrine cell type has been
      characterized in the macaque monkey retina by intracellular injection of
      horseradish peroxidase (HRP). This cell type was recognized by its large soma in
      an in vitro, wholemount preparation of the retina stained with the fluorescent
      dye, acridine orange. HRP-fills revealed a large, sparsely branching, spiny
      dendritic tree and a number of extremely thin, axon-like processes that arose
      from the soma and proximal dendrites. The axon-like processes were studded with
      distinct varicosities and were traced for up to 3 mm beyond the dendritic tree.
      The true lengths of the axon-like processes were greater than 3 mm, however,
      because the HRP reaction product consistently diminished before an endpoint was
      reached. Both the dendrites and the axon-like processes were narrowly stratified
      close to the outer border of the inner plexiform layer, although in a few cases
      single axon-like processes projected into the outer nuclear and outer plexiform
      layers. The HRP-filled amacrines appeared equivalent to a subpopulation of
      neurons that are intensely immunoreactive for tyrosine hydroxylase (TH). TH
      immunoreactive cells showed a nearly identical soma size and dendritic field size
      range, the same pattern of dendritic branching and spiny morphology, and also
      gave rise to distinct axon-like processes from both the soma and proximal
      dendrites. To test this correspondence more directly, the large acridine stained
      cells were injected with Lucifer Yellow and the retina was subsequently processed
      for TH immunoreactivity using diaminobenzidine as the chromagen. In all cases
      Lucifer Yellow injected cells also showed intense TH immunoreactivity. Spatial
      densities of the TH amacrine cells were therefore used to calculate coverage
      factors for the dendritic trees and for the axon-like components of the HRP
      filled cells. The axon-like processes showed a coverage factor of at least 300,
      about 100 times that of the dendritic fields. This great overlap could be
      directly observed in TH-immunoreacted retinal wholemounts as a dense plexus of
      fine, varicose processes. The density of the TH plexus is greater than the
      density predicted from the lengths (1-3 mm) of the HRP-filled axon-like processes
      however, and suggests that the axon-like processes have an actual length of about
      4-5 mm.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1979794
TI  - Perennial allergic rhinitis: clinical efficacy of a new antihistamine.
AB  - Nasal itching, sneezing, and rhinorrhea are troublesome symptoms in patients with
      perennial allergic rhinitis. Most first-generation H1-receptor agonists achieve a
      50% reduction in these symptoms, but their benefits are frequently offset by
      annoying anticholinergic and sedative side effects. Cetirizine is a major
      metabolite of hydroxyzine that has little anticholinergic activity and causes
      significantly less sedation. In addition, it can be given once a day. In placebo
      controlled comparisons with terfendadine, both active drugs were comparably
      effective and significantly better than placebo in relieving sneezing,
      rhinorrhea, and nasal itching. In a multicenter, double-blind comparison with
      placebo, both cetirizine, 10 and 20 mg given once daily, were similarly effective
      and superior to placebo in reducing the overall symptoms of rhinitis. In another
      multicenter, double-blind study, cetirizine was comparable with diphenhydramine
      and significantly superior to placebo in reducing total symptom severity,
      sneezing, rhinorrhea, and ocular itching. The safety of cetirizine was
      demonstrated in all studies. Cetirizine tended to be less sedating than
      diphenhydramine.

PMID- 1979795
TI  - Urticaria: current therapy.
AB  - Although the ideal treatment for urticaria is identification and removal of its
      cause, no underlying cause can be discerned in the majority of instances. The
      chief clinical problem is the treatment of chronic idiopathic urticaria. H1
      receptor antagonists are the major class of therapeutic agents used in the
      management of chronic idiopathic urticaria. The H1 antagonists have been divided
      into subgroups based on their chemical structure. The second-generation H1
      antagonists now available are particularly advantageous for individuals who must
      remain alert while working. Terbutaline, a beta-adrenergic agonist, is of
      occasional benefit as an adjunct therapy in combination with an H1 antagonist.
      The oral administration of disodium cromoglycate is ineffective in patients with
      chronic idiopathic urticaria, although a few individuals with urticaria caused by
      food allergy may respond to this drug. It is best to avoid repeated injections of
      epinephrine and the systemic administration of corticosteroids. Urticaria has a
      capricious course: it may respond to the administration of placebos or it may
      resolve spontaneously. About 50% of the patients with urticaria are free of
      lesions within 1 year, but 20% continue to have episodes for more than 20 years.

PMID- 1979793
TI  - H1-receptor antagonist treatment of seasonal allergic rhinitis.
AB  - H1-receptor antagonists are usually first-line treatment given for seasonal
      allergic rhinitis. However, many patients suffer with symptoms of allergic
      rhinitis rather than tolerate the sedative and anticholinergic side effects of
      the first-generation H1-receptor antagonists. Researchers have sought to replace
      these older H1-receptor antagonists with a new generation of H1-receptor
      antagonists that approach the optimal therapy: clinically effective, safe, free
      of side effects, and convenient for the patient. Among the new second-generation
      H1-receptor antagonists are terfenadine and astemizole (already marketed) and
      loratadine and cetirizine, which are expected to be approved soon. All four
      demonstrate efficacy, convenience, and minimal side effects on the central
      nervous system. In this review of the current treatment of seasonal allergic
      rhinitis, the clinical studies that compare these four new second-generation H1
      receptor antagonists are discussed.

PMID- 1979796
TI  - Urticaria: clinical efficacy of cetirizine in comparison with hydroxyzine and
      placebo.
AB  - Chronic urticaria is a problem for both physician and patient. In an effort to
      avoid the risks associated with corticosteroid treatment, many first-generation
      H1-receptor antagonists have been tried and found to induce undesirable levels of
      sedation when given in amounts sufficient to control urticaria. Cetirizine, a
      pharmacologically active oxidized metabolite of hydroxyzine, was developed to
      provide selective H1-receptor inhibition without depression of the central
      nervous system. In a 4-week, multicenter, double-blind, placebo-controlled safety
      and efficacy study, cetirizine, in a once-a-day dose (5 to 20 mg), was equivalent
      in efficacy to hydroxyzine in divided doses (25 to 75 mg/day). The incidence of
      somnolence in the cetirizine group was not significantly different from that of
      the placebo group. However, in the hydroxyzine group, the incidence of somnolence
      was significantly higher than that in the placebo group (p = 0.001). The results
      of this study demonstrate that cetirizine has a greater safety margin over the
      older parent drug hydroxyzine.

PMID- 1979798
TI  - Cetirizine: actions on neurotransmitter receptors.
AB  - First-generation H1-antagonist antihistamines, such as hydroxyzine, have the
      ability to cross the blood-brain barrier and cause sedation, which limits their
      usefulness in the treatment of allergic disorders. Cetirizine, a carboxylated
      metabolite of hydroxyzine, possesses the parent compound's antihistaminic
      activity but causes less sedation. We compared the activity of cetirizine at
      central H1 sites with that of hydroxyzine and terfenadine. We also compared the
      ability of cetirizine and three antihistamines to cross the blood-brain barrier.
      In each case we found that the drug's potency at H1 receptors in the central
      nervous system was similar to its activity in displacing H1 receptors in the
      lung. However, the selectivity for H1 receptors varied widely from drug to drug.
      Cetirizine did not bind at any of the receptors investigated, except H1 sites,
      even at concentrations as high as 10 mumol/L. Hydroxyzine and dexchlorpheniramine
      and, to a lesser extent, terfenadine crossed the blood-brain barrier in
      significant amounts. Cetirizine passed into the central nervous system only half
      as readily as terfenadine. These findings suggest that cetirizine's low incidence
      of sedative effects is most likely caused by its diminished potential to cross
      the blood-brain barrier and also may be partly the result of its greater
      selectivity for H1 receptors, compared with its effect at other receptors that
      may be involved in sedation.

PMID- 1979797
TI  - The effects of antihistamines beyond H1 antagonism in allergic inflammation.
AB  - Antigen and cold dry air were used to challenge the upper and lower airways,
      skin, and conjunctiva. In each of these four systems an immediate and late-phase
      reaction to antigen is well characterized. Although the pattern of mediator
      release is different in these four areas, the degree of infiltration of basophils
      and eosinophils in the late-phase reaction appears to be constant. Of a number of
      drugs that can influence these mediators and cell responses, the steroids
      represent a typical mode of action. Steroids block the late-phase response and
      ablate the eosinophil and basophil infiltration. Although the effects of
      antihistamines appear to be similar, they do not appear to be caused by H1
      antagonism; the mechanism of their action is unknown. This discussion will focus
      on these non-H1 antagonist effects of antihistamines in four challenge models,
      particularly the upper airways and skin.

PMID- 1979799
TI  - A review of the effects of antihistamines on mental processes related to
      automobile driving.
AB  - The newer, second-generation H1-receptor antagonists have been shown to have
      potent antiallergic effects without inducing sleepiness. However, because
      traditional antihistamines may cause functional or cognitive impairment, the
      clinician still must consider warning patients about activities that could be
      hazardous. Because the effects of drugs on driving an automobile are difficult to
      measure directly, studies must use surrogate activities in a laboratory setting.
      Effects of antihistamines on the central nervous system are assessed with
      psychomotor tests, which are selected on the basis of their relativity to real
      world activities, to develop a profile of mental processes that may be affected.
      This article reviews the psychomotor tests and study design used to characterize
      the intensity and duration of drug effects after single and multiple doses and in
      combination with other impairing agents such as ethanol. Several studies have
      been published that assess the effects of cetirizine, an H1-receptor blocker, on
      mental performance. In the study discussed here, diphenhydramine hydrochloride
      and hydroxyzine were used as positive controls to demonstrate that the period
      during which some traditional antihistamines impair performance is different than
      the period of reported drowsiness they induce. The results of this series of
      studies show that cetirizine induced minimal changes in mental performance tests
      and only following the highest (20 mg) dose studied.

PMID- 1979800
TI  - Cetirizine: antiallergic therapy beyond traditional H1 antihistamines.
AB  - For three decades, traditional H1 antihistamines have been used in the treatment
      of allergic diseases. They are effective in reducing histamine-related symptoms,
      but the use of such agents has been limited by sedation and anticholinergic side
      effects. These adverse effects are fewer with the recently introduced H1
      antihistamines. One of these, cetirizine, a human metabolite of hydroxyzine, is
      characterized by its high selectivity for the H1 receptor site and its reliable
      and consistent inhibition of histamine-induced allergic reactions. It also blocks
      eosinophil infiltration to the site of allergen-induced cutaneous reactions.
      Cetirizine has proved effective in the treatment of seasonal and perennial
      allergic rhinitis and urticaria. It is excreted primarily by renal mechanisms. It
      is well tolerated by elderly patients. Cetirizine has a low rate of penetration
      of the blood-brain barrier, and it has minimal central nervous system impairment.
      Furthermore, it can be given once a day. Cetirizine's low incidence of sedation
      and anticholinergic side effects contribute to its high profile of safety. In
      this article the characteristics, pharmacology, pharmacokinetics, and mode of
      action of cetirizine are reviewed.

PMID- 1979801
TI  - Advancements in antiallergic therapy: beyond conventional antihistamines. Naples,
      Florida, October 12-15, 1989. Proceedings.

PMID- 1979802
TI  - Recent advances in H1-receptor antagonist treatment.
AB  - The second-generation H1-receptor antagonists terfenadine, astemizole,
      loratadine, and cetirizine are important first-line drugs for the relief of
      symptoms in patients with allergic rhinoconjunctivitis or chronic urticaria and
      may eventually supplant the potentially sedating first-generation H1-receptor
      antagonists in the treatment of these disorders. Terfenadine, astemizole,
      loratadine, and cetirizine produce an incidence of central nervous system and
      anticholinergic adverse effects similar to that produced by placebo. Our ability
      to use H1-receptor antagonists optimally has been greatly enhanced by recent
      pharmacokinetic and pharmacodynamic studies of these medications.

PMID- 1979803
TI  - Effects of cytosine methylation at restriction sites on deoxyribonucleic acid
      (DNA) typing.
AB  - The effects of endogenous 5-methylcytosines on deoxyribonucleic acid (DNA)
      fingerprints were studied. Analysis with methylation-sensitive restriction
      endonuclease Sau3AI and its methylation-insensitive isoschizomer MboI showed some
      differences in the patterns generated as a result of 5-methylcytosines at the
      recognition sites. Moreover, a few bands of sperm DNA did not match those of
      blood DNA from the same individual, a phenomenon only observed in the digests of
      methylation-sensitive endonucleases. These findings indicate the unsuitability of
      methylation-sensitive restriction endonucleases for DNA fingerprinting and other
      forms of DNA typing, because of the tissue-specific status of the methylation.

PMID- 1979804
TI  - Brain markers and suicide: can a relationship be found?
AB  - Recent work suggests that some persons who commit suicide have altered
      neurochemistry in their brains. It remains unclear which of the many reported
      abnormalities are most reliably present and whether they reflect a specific
      psychiatric disorder or a disposition to violent impulsivity. A number of
      technical and interpretive problems must be clarified, but a postmortem test
      indicating that a subject was at high risk for suicide may eventually emerge.
      This approach would not be useful for ruling out suicide, since altered
      neurochemistry is not likely to be involved in every case.

PMID- 1979805
TI  - Binding of K99 fimbriae of enterotoxigenic Escherichia coli to pig small
      intestinal mucin glycopeptides.
AB  - Binding of purified K99 fimbriae to cryostat sections of pig small intestine was
      detected. Binding sites were located in the mucus layer, but not in the
      submucosal connective tissue. High-Mr mucin glycopeptides from pig small
      intestine were found to bind to K99-fimbriated enterotoxigenic Escherichia coli,
      in contrast to non-fimbriated cells. Sialic acid specificity of K99 fimbriae was
      demonstrated by the significant reduction in binding upon desialylation of mucin
      glycopeptides. The binding was saturable and the dissociation constant was
      estimated to be 6 x 10(-7) M. Fimbriated bacteria were calculated to possess 2.3
      x 10(3) binding sites per cell.

PMID- 1979806
TI  - Correlation between ribosomal DNA polymorphism and electrophoretic enzyme
      polymorphism in Yersinia.
AB  - Ribosomal DNA (rDNA) polymorphism was compared with electrophoretic enzyme
      polymorphism for the intra- and interspecies differentiation of Yersinia
      enterocolitica, Y. pseudotuberculosis, Y. intermedia, Y. aldovae, Y.
      frederiksenii and Y. kristensenii. DNA from 90 strains previously classified into
      six zymotypes (Y. enterocolitica and Y. frederiksenii) and into distinct enzyme
      electrophoretic patterns (the four other species) was digested with EcoRI or
      HindIII and analysed by Southern blotting. The six species were clearly
      differentiated from each other. In Y. enterocolitica, the subclassification of
      biotype 1 into zymotypes 1A and 1B was also reflected in the rDNA and the four
      other bio-zymotypes gave four different classes of restriction pattern. In Y.
      frederiksenii, both EcoRI and HindIII gave five distinct riboclasses which
      correlated with the zymotypes. In the four other species, the phenotype
      polymorphism appeared to be better correlated with the restriction fragment
      length polymorphism data in some enzymes than others. The data demonstrate that
      the inter- and intraspecies classification by rDNA polymorphism using two
      restriction enzymes is similar to that based on electrophoretic enzyme
      polymorphism. The analysis could be refined for taxonomic and epidemiological
      purposes by using other restriction enzymes.

PMID- 1979807
TI  - Effect of dietary alpha-linolenic acid on growth, metastasis, fatty acid profile
      and prostaglandin production of two murine mammary adenocarcinomas.
AB  - The purpose of this study was to determine whether dietary (n-3) fatty acids
      would affect mammary tumor growth and metastasis. Weanling female BALB/c mice
      were fed diets that contained 10% corn oil (CO), linseed oil (LO) or a fish oil
      corn oil mix (FO) for 3-8 wk prior to receiving subcutaneous injections of one of
      two syngeneic mammary tumor cell types (410 and 410.4). Tumor growth was assessed
      by monitoring mean tumor diameter and tumor weight upon removal. Feeding LO, but
      not FO, reduced the growth (p less than 0.05) of 410.4 mammary tumors compared
      with growth in those fed CO. Metastasis data paralleled the tumor growth rate.
      Feeding LO and FO enhanced (p less than 0.005) incorporation of (n-3) fatty acids
      into tumors. Tumor prostaglandin E (PGE) production was reduced (p less than
      0.005) by LO and FO, compared with CO. FO feeding reduced 410.4 tumor PGE
      synthesis more (p less than 0.05) than LO feeding, yet tumor growth was only
      inhibited by LO. These data suggest an inhibitory effect of dietary linolenic
      acid [i.e., 18:3 (n-3)] on mammary tumor growth and metastasis. However, this
      effect did not directly correlate with diet-induced changes in PGE synthesis.

PMID- 1979808
TI  - Ractopamine increases total and myofibrillar protein synthesis in cultured rat
      myotubes.
AB  - The ability of the phenethanolamine (beta-adrenergic agonist) ractopamine to
      stimulate cellular protein accretion and protein synthesis in cultured muscle
      cells was evaluated. ELC5 myoblasts (a subclone of rat L6 cells) were
      proliferated in culture (Dulbecco's Modified Eagle Medium plus 10% fetal bovine
      serum at 37 degrees C) to confluency and then allowed to differentiate to form
      myotubes. Myotubes were then further incubated in the presence of 10(-9), 10(-8),
      10(-7), 10(-6) or 10(-5) mol/L ractopamine. A significant (p less than 0.05)
      response in cellular protein accretion was observed for the 10(-6) and 10(-5)
      concentrations when compared to 10(-8) and 10(-9) mol/L ractopamine. Ractopamine
      at 0 and 10(-6) mol/L was used to examine the effect of the beta agonist on
      [35S]methionine incorporation (protein synthesis) into total cellular protein, 43
      kDa proteins and myosin heavy-chain (200 kDa) protein. Protein synthesis in
      response to beta agonist treatment was measured at 4, 24, 48, 72 and 96 h after
      ractopamine addition to the ELC5 myotubes in culture. Ractopamine (10(-6) mol/L)
      increased [35S]methionine incorporation (apparent protein synthesis) at 24 h (p
      less than 0.01), 48 h (p less than 0.05), 72 h (p less than 0.01) and 96 h (p
      less than 0.05) in cultured ELC5 muscle cells. Ractopamine also increased
      apparent protein synthesis rate of the 43-kDa proteins (p less than 0.05) and
      myosin heavy-chain protein (200 kDa) (p less than 0.05). These results indicate
      that ractopamine-enhanced ELC5 myotube protein accretion is mediated, at least in
      part, by stimulating cellular protein synthesis.

PMID- 1979809
TI  - Alpha-2 adrenergic activity of bromocriptine and quinpirole in chicken pineal
      gland. Effects on melatonin synthesis and [3H]rauwolscine binding.
AB  - In the pineal gland and retina of chickens, serotonin N-acetyl-transferase (NAT)
      activity and melatonin content are modulated by different receptors, alpha-2
      adrenergic receptors in pineal gland and D2-dopamine receptors in retina. The
      effect of two D2-dopamine receptor agonists, bromocriptine and quinpirole (LY
      171555), on melatonin synthesis in these tissues was investigated. Systemic
      administrations of bromocriptine and quinpirole decreased nocturnal NAT activity
      and melatonin content of both pineal gland and retina. Bromocriptine was
      equipotent in the two tissues, whereas quinpirole was approximately 100-fold more
      potent in retina than in pineal gland. In pineal gland, the suppressive effects
      of bromocriptine and quinpirole on NAT activity were blocked by yohimbine, a
      selective alpha-2 adrenergic receptor antagonist, but not by spiperone, a D2
      dopamine receptor antagonist. In contrast, bromocriptine- and quinpirole-induced
      decreases of the enzyme activity in retina were antagonized by spiperone, and not
      affected by yohimbine. The nocturnal increase of NAT activity of pineal glands in
      vitro was inhibited with an order of potency clonidine greater than bromocriptine
      greater than quinpirole. Additionally, bromocriptine and quinpirole displaced the
      specific binding of [3H]rauwolscine, an alpha-2 adrenergic receptor antagonist,
      to membranes from chicken pineal gland, with potencies comparable to those
      observed for inhibition of NAT activity in vitro. It is suggested that
      bromocriptine and quinpirole, in addition to their D2-dopaminergic activity, can
      stimulate alpha-2 adrenergic receptors in pineal gland of chicken.

PMID- 1979810
TI  - Effects of chronic norepinephrine administration on sympathetic neurotransmission
      in the isolated perfused rat kidney.
AB  - The effects of chronic NE administration (100 micrograms/kg/hr s.c., 6 days) on
      the stimulus-induced overflow of neurotransmitter from the isolated perfused rat
      kidney were examined. This treatment increased renal NE content and increased the
      absolute stimulus-induced overflow of NE. The increase in absolute overflow was
      not simply the result of the increase in renal NE content as fractional overflow
      was also increased slightly (20%). Alpha adrenoceptor blockade with phentolamine
      eliminated the NE treatment-induced difference in fractional overflow. However,
      the dose-response curves to phentolamine and the alpha-2 adrenoceptor agonist UK
      14,304 on stimulus-induced overflow from the kidney were not significantly
      different after NE treatment. Chronic EPI treatment (same dose) produced an 80%
      increase in fractional stimulus-induced overflow of neurotransmitter but the dose
      response curve to UK 14,304 was shifted only slight to the right (3-fold) of the
      control curve. No influence of prejunctional beta adrenoceptors on stimulus
      induced overflow was observed in either the control of the NE-treated group. In
      conclusion, the data regarding fractional overflow and the effects of the
      phentolamine suggest that NE treatment produces minimal change whereas EPI
      treatment produces marked decreases in the influence in prejunctional alpha
      adrenoceptors. However, although the data with UK 14,304 after NE treatment
      support this conclusion, the failure of EPI treatment to alter the dose-response
      curve to UK 14,304 does not. The apparent contradiction of the results with the
      alpha adrenoceptor agonist in the EPI-treated group as well as the large
      differences between the effects of NE vs. EPI treatment on stimulus-induced
      overflow and prejunctional alpha adrenoceptor function cannot be explained at
      this time.

PMID- 1979811
TI  - Antisecretory and antilesional effect of a new histamine H2-receptor antagonist,
      IT-066, in rats.
AB  - The effects of a new histamine H2-receptor antagonist, IT-066 (3-amino-4-[4-[4-(1
      piperidinomethyl)-2-pyridyloxy]-cis-2-++ +butenylamino]- 3-cyclobutene-1,2-dione
      hydrochloride), were investigated on the secretagogue-induced acid secretion in
      vivo and in vitro, and on experimental gastric and duodenal lesion in rats. IT
      066 (10-60 micrograms/kg) given i.v. inhibited histamine-stimulated acid
      secretion dose-dependently in gastric lumen-perfused rats, and the inhibitory
      effect was observed for about 12 hr. Famotidine (FMD) (10-60 micrograms/kg i.v.)
      also had an antisecretory effect, but the acid secretion recovered to the control
      level 4 hr after the administration. Cold stress plus indomethacin-induced lesion
      was significantly inhibited by IT-066 and FMD given i.v. 30 min before the cold
      stress plus indomethacin treatment. IT-066 given 7 hr before the cold stress plus
      indomethacin treatment also inhibited lesion formation significantly, but such
      antilesional effect was not observed with FMD. In the rat isolated gastric
      mucosal sheet, IT-066 inhibited histamine-stimulated acid secretion dose
      dependently and noncompetitively; its action was produced via a unique mechanism.
      The inhibitory effect of IT-066 remained after washing of the mucosa, and became
      more potent time-dependently. The inhibitory effects of FMD and cimetidine were
      not observed after washing the mucosa. These data suggest that IT-066 has a
      potent and long lasting antisecretory effect in vivo and in vitro, and that these
      properties are responsible for the long lasting antilesional action.

PMID- 1979812
TI  - Prostanoids modulate opioid cerebrovascular responses in newborn pigs.
AB  - The influences of opioids on pial arteriolar diameter and cortical periarachnoid
      cerebrospinal fluid prostanoid concentration were investigated in piglets with
      closed cranial windows. Methionine enkephalin (10(-12)-10(-6) M) increased pial
      arteriolar diameter (139 +/- 4, 149 +/- 3, 178 +/- 3 microns, for control, 10(
      12), and 10(-6) M, respectively). Leucine enkephalin produced similar pial
      arteriolar dilation. In contrast, dynorphin elicited dilation during normotension
      and constriction during hypotension. beta-Endorphin (10(-12)-10(-6) M) decreased
      pial arteriolar diameter (137 +/- 6, 128 +/- 6, 92 +/- 7 microns, for control,
      10(-12) and 10(-6) M, respectively). All four opioids increased cerebrospinal
      fluid 6-keto-prostaglandin (PG)F1 alpha, PGE2, PGF2 alpha and thromboxane B2.
      Indomethacin (5 mg/kg i.v.) blocked methionine and leucine enkephalin and
      dynorphin-induced pial arteriolar dilation, but potentiated beta-endorphin
      induced constriction and the constriction caused by dynorphin in hypotensive
      piglets. These data indicate that prostanoids modulate opioid effects on the
      cerebral vasculature.

PMID- 1979813
TI  - (+)-N-methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine as a discriminative stimulus
      in studies of 3,4-methylenedioxy-methamphetamine-like behavioral activity.
AB  - The stimulus properties of 3,4-methylenedioxymethamphetamine (MDMA)-like
      compounds were studied in rats trained to discriminate saline from (+)-N-methyl-1
      (1,3-benzodioxol-5-yl)-2-butanamine [(+)-MBDB] hydrochloride (7.18 mumol/kg; 1.75
      mg/kg), the alpha-ethyl homolog of MDMA. In previous experiments with (+)-MBDB as
      a test drug, complete substitution was observed for MDMA but not for (+)-lysergic
      acid diethylamide or (+)-amphetamine. In the study reported here, the (+)-MBDB
      cue generalized to MDMA and the parent drug, 3,4-methylenedioxyamphetamine. All
      three drugs exhibited a similar stereoselectivity, the (+)-isomer having potency
      greater than the (-)-isomer. By contrast, the hallucinogens, (+)-lysergic acid
      diethylamide, 2,5-dimethoxy-4-methylamphetamine and mescaline and the
      psychostimulants (+)-amphetamine and (+)-methamphetamine did not substitute for
      (+)-MBDB. Cocaine produced partial substitution. The results support the
      hypothesis that the primary behavioral activity of MDMA-like compounds is unlike
      that of hallucinogens and stimulants and may represent the effects of a novel
      drug class, given the name entactogens. Although the mechanism of action for the
      discriminative stimulus properties of MDMA-like compounds is not known, there is
      evidence that presynaptic serotonergic, but not dopaminergic, mechanisms are
      critical. Finally, 5,6-methylenedioxy-2-aminoindan a non-neurotoxic 3,4
      methylenedioxyamphetamine rigid analog that was previously found to substitute
      for MDMA but not for (+)-lysergic acid diethylamide was found in the study
      described here to substitute completely for (+)-MBDB. The N-methyl derivative 5,6
      methylenedioxy-2-methylminoindan produced similar results. The demonstration of
      entactogen-like discriminative stimulus properties, for drugs devoid of neuronal
      degenerative toxicity potential, serves as evidence of the independent mechanisms
      for these effects in rats.

PMID- 1979814
TI  - Neuroleptics and learning: effects of haloperidol, molindone, mesoridazine and
      thioridazine on the behavior of pigeons under a repeated acquisition procedure.
AB  - The purpose of the present study was to examine the effects of haloperidol (0.3
      10 mg/kg), molindone (0.3-5.6 mg/kg), mesoridazine (0.3-10) and thioridazine (0.3
      25 mg/kg) on the behavior of pigeons exposed to a repeated acquisition procedure.
      At sufficiently high doses, each of these neuroleptics increased error rates
      (interfered with learning) and reduced rate of responding. When the drugs were
      compared on the basis of absolute doses administered, haloperidol disrupted
      behavior at doses considerably lower than the other drugs. If, however,
      chlorpromazine equivalent doses were examined, haloperidol was the least
      disruptive of the four drugs. Comparing the degree of behavioral disruption
      produced by the four drugs with their relative neuroreceptor affinities for
      dopamine D-2, cholinergic muscarinic, histamine H1, alpha-1 adrenergic and alpha
      2 adrenergic receptors suggests that behavioral disruption cannot be attributed
      in any simple way to dopamine or acetylcholine receptor blockade. The
      relationship between the behavioral effects of neuroleptics and their simple
      neuropharmacological actions must be considered as highly tentative.

PMID- 1979815
TI  - Effect of aging on alpha-1 adrenergic stimulation of phosphoinositide hydrolysis
      in various regions of rat brain.
AB  - The effects of aging were examined on the ability of alpha-1 adrenergic receptor
      agonists to stimulate phosphoinositide hydrolysis in three brain regions. Tissue
      minces of thalamus, cerebral cortex and hippocampus from 3-, 18- and 28-month-old
      male Fischer 344 rats were prelabeled with [3H]myoinositol. Exposure of these
      prelabeled minces to phenylephrine and (-)-norepinephrine revealed that
      accumulation of [3H]inositol phosphates was selectively reduced by 20 to 30% in
      the thalamus and cerebral cortex of the oldest age group. Analysis of
      concentration-response and competition binding curves indicated that this
      decrease was due to diminished agonist efficacy rather than diminished receptor
      affinity. The reduction in responsiveness to phenylephrine and (-)-norepinephrine
      in the cerebral cortex and the lack of any changes in the hippocampus parallel
      previously reported changes in the density of alpha-1 adrenergic receptors with
      aging. These data indicate that the ability of alpha-1 adrenergic receptor
      agonists to stimulate phosphoinositide hydrolysis is reduced in some, but not
      all, brain regions of aged Fischer 344 rats.

PMID- 1979817
TI  - Dual effect of amiodarone on mitochondrial respiration. Initial protonophoric
      uncoupling effect followed by inhibition of the respiratory chain at the levels
      of complex I and complex II.
AB  - The effects of amiodarone on the respiration of isolated mouse liver mitochondria
      have been determined. Amiodarone (200 microM) had a biphasic effect on state 4
      respiration supported by either glutamate plus malate or succinate. Initially,
      the respiratory rate was increased. This stimulatory effect was not prevented by
      oligomycin (an inhibitor of ATP synthase). It was associated with marked
      accumulation of amiodarone in the mitochondria, and with collapse of the
      mitochondrial membrane potential. This initial uncoupling effect was followed by
      a progressive decrease in the state 4 respiration rate, leading eventually to
      marked inhibition. Preincubation for 5 min with amiodarone (200 microM) also
      decreased markedly ADP-stimulated (state 3) respiration, ATP production and
      dinitrophenol-stimulated (uncoupled) respiration supported by glutamate plus
      malate (which donate electrons to complex I), and respiration supported by
      succinate (which donate electrons to complex II), but did not affect respiration
      supported by duroquinol (donating electrons to complex III) or by ascorbate plus
      N,N,N',N'-tetramethyl-p-phenylenediamine (donating electrons to cytochrome c).
      Preincubation with amiodarone (150-200 microM) decreased markedly respiration
      mediated by fatty acids of various chain length and respiration mediated by
      citrate, a tricarboxylic acid cycle substrate. We conclude that amiodarone has a
      dual effect on mitochondrial respiration. The initial uncoupling effect is
      probably due to the entry of protonated amiodarone, releasing a proton in the
      matrix. Accumulation of amiodarone soon leads to inhibition of the respiratory
      chain at the levels of complex I and complex II and to decreased ATP formation.

PMID- 1979816
TI  - Respiratory effects of benzodiazepine-related drugs in awake rhesus monkeys.
AB  - The respiratory effects of several benzodiazepine (BZ) agonists and inverse
      agonists were compared with those of buspirone and pentobarbital in awake rhesus
      monkeys. Subjects, fitted with a helmet that served as a pressure displacement
      plethysmograph, were studied in a ventilated, sound-attenuating chamber;
      ventilatory frequency, tidal volume (VT) and minute volume (VE) were determined
      from the plethysmograph signal. During experimental sessions monkeys inhaled
      either 5% carbon dioxide (CO2) mixed in air or air alone according to a fixed
      alternating schedule. BZ agonists (alprazolam, 0.01-1.0 mg/kg; lorazepam, 0.3
      10.0 mg/kg; quazepam, 1.0-5.6 mg/kg) decreased VT and VE during both 5% CO2 and
      air inhalation. Pentobarbital (3.0-30.0 mg/kg) also decreased VT and VE and
      additionally decreased respiratory frequency in monkeys breathing 5% CO2. Two BZ
      inverse agonists, the beta-carbolines beta-CCE and FG 7142 (0.3-5.6 or 10.00
      mg/kg), increased frequency and had no effect on VT, resulting in an increase in
      VE in monkeys breathing either 5% CO2 or air. The weak BZ inverse agonist CGS
      8216 (0.3-5.6 mg/kg) similarly increased ventilation only in monkeys breathing
      air. Buspirone (0.03-0.3 mg/kg), like the beta-carbolines, increased frequency
      and VE and, like the BZ agonists, decreased VT. The BZ antagonist Ro15-1788 (0.1
      3.0 mg/kg) had little or no effect on ventilation, but Ro15-1788 and also CGS
      8216 (both at 1.0 mg/kg) attenuated the respiratory depressant effects of
      lorazepam or alprazolam. In turn, alprazolam (0.03-0.3 mg/kg) and quazepam (1.0
      3.0 mg/kg) attenuated the respiratory stimulant effects of FG 7142.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1979818
TI  - Hypertension, coronary risk and alpha-blockade.

PMID- 1979819
TI  - Alpha 1-adrenoreceptor blockade and the molecular basis of lipid metabolism
      alterations.
AB  - For the past 40 years, adrenoreceptors have been studied as the biomolecular
      mediators of tissue response to catecholamines. An expanded role of alpha
      adrenoreceptors in the regulation of risk factors for coronary heart disease
      (CHD) has recently emerged. Hypercholesterolaemia, hypertension, and cigarette
      smoking are the major risk factors and their interactions are associated with
      increased mortality. Control of hypertension alone has failed to reduce the risk
      of CHD. Conversely, reduction of elevated total cholesterol and low density
      lipoprotein (LDL)-cholesterol has been shown to lower the risk of CHD. As a
      result, multiple risk factor approaches to the management of patients have
      evolved in attempts to reduce deaths from CHD. Selective alpha 1-adrenoreceptor
      antagonists appear to have a dual function in CHD risk management since they
      control elevated blood pressure by peripheral vasodilatation and reduce
      atherogenic lipids by several mechanisms. With selective alpha 1-blockade, the
      number of LDL-cholesterol receptors is up-regulated and 3-hydroxy-3
      methylglutaryl coenzyme A reductase (HMG Co-A reductase) activity is suppressed
      causing reductions in total cholesterol, LDL-cholesterol, and apoprotein B
      levels. Effects on intermediary metabolism reduce synthesis of very low density
      lipoprotein (VLDL) which contributes to a reduction of total triglyceride levels
      and, to a lesser extent, to a reduction of total cholesterol levels. Increased
      lipoprotein lipase activity leads to reduced total triglyceride and VLDL levels
      and to increased high density lipoprotein (HDL)-cholesterol levels. As
      demonstrated by the initial prospective data from Phase I of the Treatment of
      Mild Hypertension Study (TOMHS), both reduction of raised blood pressure and
      beneficial lipid modifications are sustained (1 year) with selective alpha 1
      blockade. The prospective benefits on morbidity and mortality from CHD of such
      favourable changes in these two major risk factors remain to be quantified.

PMID- 1979820
TI  - Doxazosin in 'resistant' hypertension.
AB  - A study of doxazosin added to baseline therapy with a beta-adrenoceptor blocker
      plus a diuretic in the treatment of patients 'resistant' to the baseline therapy,
      showed that it was effective and generally well tolerated. The study was,
      however, open-label and lacked comparison with other third-line drugs.

PMID- 1979821
TI  - Antihypertensive drugs and the hypertensive diabetic patient.
AB  - Hypertension occurs in about 40% of patients with non-insulin-dependent diabetes
      mellitus (NIDDM) in whom the incidence of coronary heart disease is greatly
      increased. Disturbances in lipid metabolism may be an important contributory
      factor. Patterns of lipid change in uncomplicated NIDDM are characterised by a
      raised serum triglyceride and a reduced high density lipoprotein. It is therefore
      likely that therapy for hypertension associated with NIDDM may further influence
      an existing atherogenic lipid profile. Recent studies in diabetic subjects have
      shown that alpha-blockers are associated with a trend towards improving, while
      beta-blockers adversely affect, the lipid profile. Calcium antagonists and ACE
      inhibitors have no adverse effects on the lipid profile.

PMID- 1979822
TI  - Cytoplasmic male sterility in beta is associated with structural rearrangements
      of the mitochondrial DNA and is not due to interspecific organelle transfer.
AB  - Chloroplast (ct) and mitochondrial (mt) DNAs from four cytoplasmic male sterile
      (cms) and 22 normal fertile sugar beet lines and accessions of wild beets from
      the genus Beta have been compared with restriction analyses and Southern
      hybridizations. We have used restriction analyses of ctDNA as a phylogenetic
      marker to confirm the taxonomic relationships between the different cytoplasms.
      According to the ctDNA data, all four cms cytoplasms belong to the same taxonomic
      section, Beta. Restriction patterns of ct and mtDNA from fertile accessions
      produced analogous trees of similarity and showed a close correlation between the
      organellar DNA diversity and the accepted taxonomic classification of the species
      studied. However, the mt-DNA restriction profiles of the four cms types differed
      dramatically from each other and from those of all fertile accessions from the
      genus. No indication of cytoplasmic introgression was found in any of the four
      investigated cms types. Southern hybridization to mtDNA revealed variant genomic
      arrangements in the different fertile and cms cytoplasms, indicating that
      rearrangement of the mitochondrial genome is a common denominator to the
      different cms systems in Beta. It may, indeed, be a common property to
      spontaneously occurring cms in all or most species.

PMID- 1979823
TI  - Fate of ingested immunoglobulin G in the mosquito Aedes aegypti (Diptera:
      Culicidae).
AB  - The amount of bloodmeals ingested by Aedes aegypti was estimated to be 3.00 +/-
      1.05 mg (2.84 +/- 0.99 microliters) in average. The feeding time of a mosquito
      was not necessarily associated with the quantity of the bloodmeal. Nevertheless,
      the number of egg laid after bloodfeeding was apparently dependent on the volume
      of ingested bloodmeals. The change of immunoglobulin G (IgG) in the ingested
      bloodmeals of Aedes aegypti was also evaluated by ELISA. To detect the survival
      of ingested IgG, 5-day-old adult female mosquitoes were allowed to feed on a
      human arm. After completion of feeding, 3 engorged mosquitoes were selected on
      the basis of 6-hour intervals until the 54th hour post ingestion. Selected
      specimens were deprived of their legs and wings, homgenized and centrifuged. The
      supernatants were collected for ELISA procedure. The control groups included the
      blank (PBS) and unfed mosquitoes. All OD405 values representing the amount of IgG
      in the ingested bloodmeal were evaluated as 1.702 +/- 0.017, 0.469 +/- 0.046,
      0.414 +/- 0.084, 0.231 +/- 0.012, 0.180 +/- 0.025, 0.172 +/- 0.006, 0.163 +/-
      0.012, 0.173 +/- 0.007, 0.168 +/- 0.012, and 0.169 +/- 0.014, respectively for
      each interval. A blood sample taken from the same person fed to mosquitoes was
      evaluated to be 1.716 +/- 0.012. The OD405 values of the blank and the unfed
      group were 0.156 +/- 0.019 and 0.159 +/- 0.009, respectively. The result showed
      that IgG ingested by Aedes aegypti may be digested vigorously within 6
      hours.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1979825
TI  - [Proceedings of the 31st annual meeting of Japan Geriatrics Society].

PMID- 1979824
TI  - [Recent advances in human molecular genetics].
AB  - The haploid nucleus of a human cell contains 3 X 10(9) base pairs. Organized in
      linear duplex, this DNA would stretch out to a length of some 90 cm. Thus,
      organization of chromosomes has been a major subject for pioneer cytogenetists.
      Long lasting controversies on the strandedness of chromosomes, together with
      newly developed banding techniques, led us to molecular cytogenetics. Next, the
      discovery of reverse transcriptase, restriction endonucleases, and other
      recombinant DNA methods have enabled us to isolate and characterize genes from
      any organism and to determine the DNA sequences and any encoded protein
      sequences. These new technologies have already helped us to understand many
      inherited diseases at a molecular level. In sickle cell anemia, thalassemia and
      in other mendelian disorders we can know their molecular defects by examining the
      DNA from peripheral leukocytes, without the need for complex biochemical assays
      or biopsies. Southern blot analysis using restriction endonuclease and a probe is
      a basic tool for molecular diagnosis. cDNA or DNA fragments are used as probes.
      Recently, synthesized oligonucleotide probes are available, if the DNA sequence
      of a gene is determined. In addition, restriction fragment length polymorphisms
      (RFLPs), play a very important role in the molecular diagnosis. Linkage analysis
      using RFLPs linked to the gene locus of a certain disease also permits the
      detection of the patients and carriers within families with genetic diseases of
      unknown cause. Starting with the genetic map and physical map, genes for cystic
      fibrosis and Duchenne muscular dystrophy have recently been isolated and cloned.

PMID- 1979826
TI  - [A case of nephrotic syndrome associated with small intestinal ulcers due to
      necrotizing angitis].
AB  - A 34-year-old man was admitted to Prier hospital because of head and right foot
      injuries caused by a traffic accident. Two months after admission, he complained
      of abdominal pain and bloody stool. Shortly after purpura appeared on both legs.
      He received an exploratory laparotomy and showed multiple jejunal ulcer. A
      pathological examination of the jejunum revealed necrotizing vasculitis of the
      small arteries. After the operation, he had arthralgia and the laboratory
      examination showed massive urinary protein. Arthralgia, abdominal pain and bloody
      stool disappeared with the administration of 100 mg per day of prednisolone
      (PSL), but nephrotic syndrome was not relieved. As a result he was referred to
      our hospital. And after admission, PSL was gradually tapered to 60 mg per day.
      Then an open renal biopsy was performed, and pathological examinations revealed
      focal proliferative glomerulonephritis in which 31% of the glomerulus showed
      fibro-cellular crescents. A direct immunofluorescence of the renal biopsy showed
      mesangial deposits of IgA, IgG, C3. The patient was treated with anti-coagulant
      therapy and PSL. Urinary protein was gradually decreased to 0.7 g/day, and his
      creatinine clearance was 23 ml/min five months after the renal biopsy. In this
      case, although the renal biopsy specimens and clinical symptoms were compatible
      with HSP, a pathological examination of jejunum revealed vasculitis of the small
      arteries. In literature, HSP is a syndrome characterized by vasculitis of
      arterioles, capillaries and venules. As a results of those findings, we think the
      diagnosis of this patient is PN with mesangial IgA depositions of renal
      glomeruli.

PMID- 1979827
TI  - Detection of D,L-amphetamine, D,L-methamphetamine, and illicit amphetamine
      analogs using diagnostic products corporation's amphetamine and methamphetamine
      radioimmunoassay.
AB  - Cross-reactivity with Diagnostic Products Corporation (DPC) amphetamine and
      methamphetamine radioimmunoassay (RIA) reagents was determined for amphetamine,
      methamphetamine, and a number of amphetamine analogs. Concentrations from 100 to
      100,000 ng/mL were assayed. 3,4-Methylenedioxyamphetamine (MDA) and 3,4
      methylenedioxymethamphetamine (MDMA) showed significant cross-reactivity for the
      amphetamine and methamphetamine reagents respectively. 4-Hydroxymethamphetamine,
      3,4-methylenedioxyethylamphetamine (MDEA), and N,N-dimethyl-MDA also showed
      significant cross-reactivity with the methamphetamine reagents, but less than
      MDMA. None of the other analogs showed a positive result with the amphetamine or
      methamphetamine reagents at even the highest concentration, although several did
      show measurable cross-reactivity. The L isomers of amphetamine and
      methamphetamine showed substantially less cross-reactivity than the D forms to
      which the respective antibody systems are targeted.

PMID- 1979828
TI  - [NGF remove grower factors and neurotransmitters in the testis--new discoveries
      in reproduction biology].

PMID- 1979829
TI  - Characterization of beta adrenoceptors on cultured endothelial cells by
      radioligand binding.
AB  - The properties of beta-adrenoceptors present on the cultured bovine pulmonary
      artery endothelial cells were studied by radioligand binding. These cell contain
      a high density of beta-adrenoceptors (approximately 16,000 receptors/cell) having
      high affinity (Kd 18 pM) for 125I-iodocyanopindolol (ICYP). Competition binding
      experiments suggested the presence of more than two subtype of beta
      adrenoceptors. 25% of the total population of receptors was found to be of beta 1
      type. The remaining 75% represented a mixed population containing what is
      suggested to be a mixture of beta 2- and atypical beta-adrenoceptors.

PMID- 1979830
TI  - Ketanserin pretreatment attenuates MDMA-induced dopamine release in the striatum
      as measured by in vivo microdialysis.
AB  - Systemic administration of the amphetamine analogue, 3,4
      methylenedioxymethamphetamine (MDMA) produced a dose-dependent increase in the
      extracellular concentration of dopamine (DA) in the striatum as measured by in
      vivo microdialysis in awake, freely-moving rats. The extracellular concentration
      of the DA metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), was significantly
      decreased in dialysate samples following the administration of MDMA (10 and 20
      mg/kg, i.p.). The serotonin-2 (5-HT2) antagonist ketanserin (3 mg/kg, i.p.) had
      no effect on the extracellular concentration of DA or DOPAC in the striatum of
      vehicle- treated rats. The administration of ketanserin (3 mg/kg) 1 hr prior to
      MDMA (20 mg/kg) significantly attenuated the MDMA- induced increase in the
      extracellular concentration of DA without affecting the decrease in DOPAC
      concentrations. These data are suggestive that MDMA administration increases DA
      release in the striatum of awake, freely-moving rats. In addition, MDMA-induced
      increase in the extracellular concentration of DA in the striatum is mediated, in
      part, via 5-HT2 receptor mechanisms.

PMID- 1979832
TI  - Evolution of beta-globin haplotypes in human populations.
AB  - The beta-globin haplotypes of 852 chromosomes from 12 populations in the Asia
      Pacific region are described. These data are combined with those from other
      populations in an investigation of the affinities of regional human populations.
      Both partial maximum-likelihood and distance Wagner methods indicate that
      Africans are the most divergent group, with the remaining populations branching
      in the following order: Australian Aborigines, Highland Melanesians, Lowland
      Melanesians, Indonesians and Micronesians, Polynesians, east Asians, Indians, and
      Europeans. This pattern of relationship is consistent with that indicated by
      other data. Analysis of the evolution and distribution of haplotype occurrence
      provides some limited support for an origin of modern humans in Africa.
      Otherwise, however, it was not useful in further elucidating the evolutionary
      history of human populations.

PMID- 1979831
TI  - Secretion of gamma-glutamyltranspeptidase by the pancreas: evidence for a
      membrane shedding process during exocytosis.
AB  - Gamma Glutamyltranspeptidase (GGT) is a membrane-bound enzyme involved in
      glutathione metabolism. It is present in rat exocrine pancreas at a level which
      is only exceeded by the kidney. It has been previously shown that most of the
      enzyme activity is located in the apical area of the acinar cell, more precisely
      at the level of zymogen granules and plasma membrane. The aim of the present
      study was to examine the secretory behavior of that enzyme. Under resting
      conditions, in vivo, high levels of GGT were found in pancreatic juice and its
      level was not related to protein concentration. Under secretin infusion, a
      relatively constant level of GGT was released, and again, there was no
      correlation between enzyme activity and protein concentration. Following a bolus
      injection of caerulein, an analog of cholecystokinin, marked and concomitant
      rises in protein and GGT levels were observed. Ultracentrifugation, as well as
      gel filtration on Sepharose 4B, demonstrated that the enzyme was not released in
      a soluble form. This observation is in agreement with in vitro determinations on
      isolated zymogen granules showing that GGT is totally associated with the ZG
      membrane and undetect-able in the content of these organelles. The present data
      show that 1 degree GGT is released from the rat pancreas acinar cells in a
      particulate form; 2 degree GGT release is elicited by hormonal stimulation
      coinciding with the exocytotic release of secretory proteins. Our observations
      lead us to propose that in rat pancreas, ZG membrane fragments are released along
      with secretory proteins during exocytosis.

PMID- 1979833
TI  - Evaluation of the mutagenicity of the anti-inflammatory drug
      salicylazosulfapyridine (SASP).
AB  - Salicylazosulfapyridine, commonly known as sulfasalazine or SASP, is an anti
      inflammatory drug that is widely used in the treatment of diseases such as
      ulcerative colitis and Crohn's disease. Increases in sister chromatid exchanges
      (SCE) and micronuclei (MN) frequencies have been reported in lymphocytes of
      patients maintained on SASP therapy for up to 21 months. We have tested SASP for
      its ability to induce chromosome aberrations (ABS) and SCE in cultured Chinese
      hamster ovary (CHO) cells, ABS in mouse bone marrow cells, and MN in erythrocytes
      from both bone marrow and peripheral blood of mice. In vitro assays for ABS and
      SCE were negative. In vivo, SASP administered by single gavage at doses up to
      1000 mg/kg did not increase ABS in bone marrow cells of male B6C3F1 mice;
      however, increases in MN were observed in the peripheral blood erythrocytes of
      male and female B6C3F1 mice administered 675, 1350 or 2700 mg/kg SASP by gavage
      for 90 days. Weak but significant dose-related increases in MN were also observed
      in the bone marrow cells of male B6C3F1 mice administered 500, 1000 and 2000
      mg/kg SASP for 3 days. These positive findings in mice support the role of SASP
      in the induction of MN and SCE in humans, and suggest the need for further
      evaluation of possible adverse human health effects associated with SASP therapy.

PMID- 1979834
TI  - Graded cytopathogenicity of the human immunodeficiency virus (HIV) in the course
      of HIV infection.
AB  - To determine whether the biological variability of HIV-1 has any clinical
      significance, the highly variable cytopathogenicity of 153 HIV-1 strains,
      isolated from 119 hemophiliacs, was related to the number of CD4+ lymphocytes
      present in the patient's blood at the time of virus isolation. It was shown that
      the cytopathogenicity of the HIV-1 isolates was inversely correlated with the
      number of CD4+ lymphocytes. The highest CD4+ cell number were observed in 34
      latently infected patients characterized by HIV seropositivity, failure of virus
      isolation, and detection of viral DNA by the polymerase chain reaction.
      Cytopathogenicity of the HIV-1 isolates was a reliable prognostic marker and
      correlated well with other less-sensitive prognostic parameters, including the
      detection of infectious virus and p24 antigen in the plasma, and the decline of
      p24 antibody in the serum. The results suggest that the viral isolates - if not
      subjected to extensive passage - represent in vivo variants selected from a
      heterogeneous viral population according to the particular immunological
      conditions of the host.

PMID- 1979835
TI  - [Restriction polymorphism in patients with lipid metabolism disorders and
      ischemic heart disease].
AB  - Using the RELP analysis we studied the frequency of X2 allele of apoB gene in
      three groups of patients: 1) men at the age of 20-59 with lipid metabolism
      disorders revealed in population inspection of Oktyabrsky district in Moscow; 2)
      men with ischaemic heart disease and 3) healthy men. It was established that in
      individuals suffering from type IIa hyperlipidemia the frequency of X2 allele was
      significantly higher than in healthy donors from Moscow population. Homozygotes
      for X2 allele of XbaI RELP had 7-9% higher serum cholesterol levels, than
      homozygotes for X1 allele. The study suggests the X2 allele of the apoB gene to
      be associated with the development of high plasma cholesterol level. No
      significant difference in X2 allele frequencies was found between patients with
      ischaemic heart disease and healthy donors. There was also no association found
      between cholesterol and triglyceride levels and the presence of X2 allele in this
      group of patients.

PMID- 1979836
TI  - [Regulation of phenylalanine biosynthesis in the obligate methylotroph
      Methylobacillus M75].
AB  - Regulation of phenylalanine biosynthesis has been studied in the bacterium
      Methylobacillus M75 on the level of enzymes 3-deoxy-D-arabinoheptulose-7
      phosphate-synthase, chorismatmutase, prephenatdehyrataze. The DAHP-synthase is
      shown to be synthesized constitutively and its activity is inhibited by all
      aromatic aminoacids and antranilate. The synthesis of chorismatmutase and
      prephenatdehydratase is repressed by tyrosine, the activity of the latter enzyme,
      besides that, is inhibited by phenylalanine, the effect of which is decreased in
      the presence of tyrosine.

PMID- 1979837
TI  - [The effect of the simultaneous dopamine- and glutamatergic stimulation of the
      nucleus accumbens on synaptic dopamine release in the striatum of freely moving
      rats].
AB  - The influence of n. accumbens on the striatal synaptic dopamine release was
      investigated in freely moving male Sprague-Dawley rats using in vivo intracranial
      dialysis followed by radioenzymatic analysis. It was shown that amphetamine or
      glutamic acid dialysis infusion in the n. accumbens resulted in a decrease in
      striatal extracellular dopamine level while simultaneous infusion of these drugs
      led to increase in striatal level of extracellular dopamine. It is suggested that
      there exist an influence of the n. accumbens on dopamine release in the striatum,
      the sign of this influence being mediated by dopamine-glutamic acid interaction
      in the n. accumbens.

PMID- 1979838
TI  - Effects of delta-9-tetrahydrocannabinol, cannabinol and cannabidiol, alone and in
      combinations, on luteinizing hormone and prolactin release and on hypothalamic
      neurotransmitters in the male rat.
AB  - The acute effects of low oral doses of delta 9-tetrahydrocannabinol (THC),
      cannabinol (CBN) and cannabidiol (CBD) administered alone or in combinations on
      LH and prolactin (PRL) secretion and on hypothalamic norepinephrine (NE),
      dopamine (DA) and serotonin (5-HT) dynamics were examined in adult male rats.
      Plasma LH levels were significantly reduced 60 min after administration of 0.5 mg
      THC/kg body weight and 30, 60 and 120 min after administration of THC + CBN or
      THC + CBD. There were no changes in plasma PRL in response to cannabinoid
      treatments. The turnover of NE in both the median eminence (ME) and medial basal
      hypothalamus (MBH) was dramatically affected by all the cannabinoid treatments.
      Complete suppression of NE turnover occurred 30 min post-THC and 120 min post-THC
      + CBN in the ME and 120 min post-THC + CBD in the MBH. Cannabinoids did not
      significantly affect DA turnover in the MBH or the content of NE, DA, 5-HT or 5
      hydroxyindole-3-acetic acid in either the ME or MBH. These data demonstrate that
      treatment of adult male rats with a low dose of THC suppresses LH secretion and
      that CBN and CBD potentiate this action of THC. Although the mechanisms
      responsible for the inhibition of LH release by cannabinoids cannot be positively
      identified from these experiments, the results suggest that alterations in
      hypothalamic noradrenergic activity may be involved in this effect.

PMID- 1979839
TI  - Somatostatin messenger RNA in hypothalamic neurons is increased by testosterone
      through activation of androgen receptors and not by aromatization to estradiol.
AB  - Growth hormone (GH) secretory patterns are influenced by sex steroids, at least
      in part, through modulation of the secretion of hypothalamic somatostatin (SS)
      and GH-releasing hormone. Neurons in the periventricular nucleus (PeN) expressing
      the messenger RNA (mRNA) for SS are modulated by physiological levels of
      testosterone. However, it is uncertain whether testosterone's action is mediated
      directly by androgen receptor activation or indirectly through aromatization to
      estradiol and subsequent binding to the estrogen receptor. We examined this
      question by evaluating the effectiveness of 17 beta-estradiol and the
      nonaromatizable androgen, dihydrotestosterone (DHT), to mimic the effects of
      testosterone. Adult male rats were castrated and implanted subcutaneously with a
      Silastic capsule that contained either testosterone, 17 beta-estradiol or DHT, or
      a sham capsule. Intact animals were sham-operated. We used in situ hybridization
      to assess the effect of these treatments on SS mRNA signal levels in individual
      neurons of the hypothalamus. Following castration, SS mRNA content was reduced in
      cells of the PeN (intact, 195 +/- 12 grains/cell, vs. castrated, 139 +/- 4
      grains/cell). Replacement with physiological levels of testosterone prevented the
      decline in SS mRNA signal levels (castrated testosterone-replaced, 214 +/- 15
      grains/cell) as did replacement with the nonaromatizable androgen DHT (castrated
      DHT-replaced, 213 +/- 16 grains/cell). Treatment with 17 beta-estradiol failed to
      prevent the postcastration decline in SS mRNA content (castrated estrogen
      replaced, 145 +/- 4 grains/cell). Castrated 17 beta-estradiol-treated animals
      were not significantly different from the castrated sham-treated animals
      (castrated, 139 +/- 4 grains/cell, vs. castrated estrogen-replaced, 145 +/- 4
      grains/cell).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1979841
TI  - Familial cerebral cavernous angiomas.
AB  - Three families with two or more members affected by cavernous angiomas of the
      brain are described and the other 17 reported in the literature are reviewed. The
      familial occurrence of cerebral cavernous angiomas has been considered a rare
      event; nevertheless, the experience of the authors (positive familiarity in three
      patients where two or more relatives have been explored radiologically) suggests
      that cavernous angiomas of the brain might be, at least in most cases, a familial
      disease. Therefore, when a patient with cerebral cavernous angioma is observed, a
      careful familial history and the exploration of the familial members by
      computerized tomography or better still by magnetic resonance must be performed.
      The high frequency of multiple lesions in familial cases, the surgical
      indications and the role of the ultrasonic prenatal diagnosis are also discussed.

PMID- 1979840
TI  - Regulation of dopamine release in vitro from the posterior pituitary by opioid
      peptides.
AB  - Opioid peptides are present in both the posterior pituitary (PP) and stalk-median
      eminence (SME). Their effects on the dopaminergic neurons in the SME are well
      documented, but little is known concerning their role in the regulation of
      dopamine (DA) release from the PP. The objectives of this study were (1) to
      develop an in vitro method suitable for examining the regulation of endogenous DA
      release from PP and SME, and (2) to describe and compare the effects of selected
      opioid peptides on potassium-evoked DA release from these tissues. Tissues were
      dissected from ovariectomized rats and incubated in media. After equilibration,
      two pulses of 28 mM potassium (K+), 3 min each, were delivered 30 min apart. Test
      substances were administered 20 min before the second K+ stimulus. DA in the
      media was determined by high-performance liquid chromatography. Potassium at 28
      and 56 mM elicited a marked increase in DA release from the PP and SME; this was
      abolished by the removal of calcium. The opioid receptor antagonist, naloxone,
      significantly increased the release of DA from both PP and SME by 55%. Dynorphin
      A elicited a significant inhibition of DA release from PP and SME by 33 and 50%,
      respectively. In contrast, methionine enkephalinamide decreased DA release from
      the SME by 50%, but was without effect in the PP. The release of DA from both PP
      and SME was significantly inhibited by beta-endorphin, and this was reversed by
      naloxone. However, beta-endorphin was fourfold more effective in the SME. N
      acetyl-beta-endorphin did not alter DA release. CONCLUSIONS: (1) we have
      developed a simple and sensitive in vitro method for studying the effects of
      hormones and drugs on the release of endogenous DA from PP and SME; (2)
      tuberoinfundibular dopaminergic and tuberohypophyseal dopaminergic nerve
      terminals are subjected to a similar inhibitory control by endogenous opioid
      peptides, and (3) exogenously applied opioid peptides exert differential effects
      on the release of DA from SME and PP which could be attributable to a dissimilar
      distribution of opioid receptor subtypes in these two tissues.

PMID- 1979842
TI  - Cerebral potentials evoked by fast head accelerations.
AB  - Fast, time optimal, voluntary horizontal head rotations produce evoked cerebral
      potentials (EPs). These show distinct amplitudes between 10 and 25 microV and
      latencies of N1 66 ms, N2 178 ms, P1 295 ms and N3 424 ms. Specifically, an
      increase in head acceleration is significantly correlated with a decrease of the
      latency of the EPs and an increase in their normalized amplitude. Control studies
      with isolated proprioceptive stimulation of the wrists and the neck with the head
      fixed provided evidence for the dominant vestibular generation of the head
      movement associated EP that is fine tuned throughout changes in head
      acceleration.

PMID- 1979843
TI  - Cerebral blood flow in experimental intracranial mass lesions. Part I: The
      compression phase.
AB  - We have shown that a rebound of intracranial pressure (ICP) occurring after
      decompression of an intracranial mass lesion is a threshold phenomenon dependent
      upon the cerebral perfusion pressure (CPP) during compression and the duration of
      the compression. In the present study regional cerebral blood flow (rCBF) was
      measured during balloon compression of a degree critical for the development of a
      postdecompression rebound. The effects were compared with those of
      hydrostatically raised pressure which under similar conditions rarely produces a
      rebound of ICP. Disproportionately marked reductions in flow occurred in the
      hemisphere ipsilateral to the balloon, especially in white matter and in cortex
      adjacent to the balloon with flow values of, respectively, 1.1 +/- 0.9 and 6.4 +/
      3.4 ml 100 g-1 min-1. The differences in flow between balloon and hydrostatic
      compression were found to be due to an increased cerebrovascular resistance (CVR)
      caused by a direct compressive effect by the balloon overriding the generalized
      vasodilation which occurs in response to the raised ICP. Thus the increase in CVR
      attributable to compression by the balloon added to the reduction in CPP caused
      by the diffuse increase in ICP. As a consequence flow in large regions of the
      brain was reduced below the thresholds for structural infarction and for
      ischaemic damage to the blood-brain barrier.

PMID- 1979844
TI  - Cerebral blood flow in experimental intracranial mass lesions. Part II: The
      postdecompression phase.
AB  - Cerebral haemodynamics were evaluated after a period of cerebral compression
      produced by subarachnoid fluid infusion or inflation of an epidural balloon.
      Release of the compression resulted in a marked cerebral hyperperfusion which was
      generalized in the case of hydrostatically raised pressure but restricted to
      supratentorial structures after balloon compression. A rebound of intracranial
      pressure (ICP) occurred only after balloon compression, indicating that loss of
      vasomotor tone per se was not the primary reason for the rebound of ICP. In the
      balloon compression experiments the hyperaemia passed into a stage of
      hypoperfusion attributable in part to a reduction in cerebral perfusion pressure
      due to the rebound of ICP and in part to an increase in flow resistance probably
      related to external compression of the vascular bed by the accumulation of brain
      oedema. The observed flow changes, i.e. delayed hypoperfusion preceded by
      hyperaemia, were similar to those after temporary ischaemia, indicating that the
      rebound response is a non-specific postischaemic phenomenon.

PMID- 1979845
TI  - Repetitive ischaemia of cat brain: pathophysiological observations.
AB  - The cumulative effect of repetitive ischaemia on brain injury was studied in
      halothane-anaesthetized cats submitted to three episodes of global cerebro
      circulatory arrest. Ischaemia of 5.0, 7.5 and 10.0 min duration was produced at
      hourly intervals by intrathoracic clamping of the innominate and subclavian
      arteries, and the resulting pathophysiological changes were evaluated by
      recordings on the electroencephalogram (EEG), blood flow and specific gravity.
      During each episode of ischaemia EEG flattened within 15 s. After ischaemia the
      latency of EEG recovery increased with the duration and with the number of
      repetitions of each ischaemic episode, indicating cumulation of
      electrophysiological impairment. The flow studies revealed a minor degree of
      hyperaemia after each ischaemic episode, followed by severe hypoperfusion in the
      caudate nucleus but not in the cerebral cortex. Brain oedema - as assessed by
      specific gravity measurements - developed in the hippocampus after three episodes
      of 5 min ischaemia, and in all grey matter structures investigated after three
      episodes of 10 min ischaemia. To evaluate the resistance of the ischaemically
      injured brain to respiratory hypoxia, total oxygen was repeatedly reduced to 5%
      for 5 min. During these episodes EEG activity progressively declined as a
      function of the length and the repetition of ischaemia. Parallel n.m.r.
      spectroscopic measurements in the same model have demonstrated that disturbances
      of brain energy state during the hypoxic episodes are minor even after three
      episodes of 10 min ischaemia. EEG suppression, in consequence, is an electrical
      shut-down phenomenon for the maintenance of cerebral energy state under critical
      conditions of oxygen delivery.

PMID- 1979846
TI  - Role of brain tissue leukotriene in brain oedema following cerebral ischaemia:
      effect of a 5-lipoxygenase inhibitor, AA-861.
AB  - It has been postulated that lipoxygenase metabolites of arachidonic acid play a
      role in the pathogenesis of cerebral ischaemia. Severe forebrain ischaemia in
      rats was induced by four-vessel occlusion with mild hypotension. After 30 min of
      ischaemia, circulation was restored by removing the arterial clamps and
      increasing blood pressure to preischaemic levels. During 30 min of cerebral
      ischaemia, free arachidonic acid increased by approximately 8.5 times compared
      with the preischaemic level. This accumulation was reversed within 60 min of
      reperfusion. The concentration of leukotriene C4 in brain tissue increased
      significantly during reperfusion: treatment with a 5-lipoxygenase inhibitor, AA
      861, decreased the increase of brain water content associated with reperfusion.
      This study demonstrated that the increased arachidonic acid resulting from
      cerebral ischaemia in rats is metabolized to leukotrienes via the lipoxygenase
      pathway once circulation is restored, and these leukotrienes may play some role
      in the development of postischaemic cerebral oedema.

PMID- 1979847
TI  - Effect of salbutamol on regional cerebral oxygen consumption, flow and capillary
      and arteriolar perfusion.
AB  - This study quantitatively determined the effect of salbutamol (1 microgram kg-1),
      a beta 2-adrenoceptor agonist, on the perfusion of the brain microvasculature,
      cerebral O2 consumption, O2 extraction and cerebral blood flow (CBF) in conscious
      rat. Indices of arteriolar and capillary structure and the percentage of the
      total cerebral microvascular volume/mm3 (% Vv) and number/mm2 (% Na) perfused
      were determined. These parameters were obtained from the perfused microvessels,
      identified by the presence of fluorescein isothiocyanate (FITC) - dextran, and
      compared with the entire microvascular bed, identified by alkaline phosphatase
      stain. Cerebral O2 extraction was determined microspectrophotometrically and CBF
      was determined using 14[C]iodoantipyrine in another group of salbutamol-treated
      rats. The acute administration of salbutamol did not alter systemic arterial
      blood pressure. Significant tachycardia was noted in the salbutamol-treated rats.
      Salbutamol resulted in a significant increase in the percentage of arterioles
      perfused. Average percentage perfused capillary Na increased significantly from
      46 +/- 2 to 88 +/- 1%; %Vv increased significantly and similarly in the
      arteriolar and capillary beds in all brain regions examined. Average cerebral O2
      consumption increased significantly from 3.0 +/- 0.2 to 7.4 +/- 0.7 ml O2 min-1
      100 g-1 with salbutamol, while cerebral O2 extraction was unchanged. Average CBF
      increased from 50 +/- 2 to 142 +/- 9 ml min-1 100 g-1 with salbutamol. Salbutamol
      may increase the perfusion of the regional microvasculature by increasing
      cerebral O2 consumption (metabolic vasodilation) and CBF and microvascular
      perfusion secondarily, although a direct effect of salbutamol on cerebral
      microvessels cannot be ruled out.

PMID- 1979848
TI  - Intracranial pressure-volume response in dog subjected to repeated infusion
      tests: an experimental study.
AB  - Several experimental studies have been made in the past to try to understand the
      nature of the fluid-induced changes in the intracranial pressures of the animals
      by infusing fluid into their craniospinal complex. The objective of the present
      investigation was to study the changes in the characteristics of the ventricular
      and epidural pressure-volume curves when a dog was subjected to repeated fluid
      infusion tests. The animals were subjected to three cycles of infusion tests with
      a time interval of either 10 min or 2 h between any two successive tests. An
      infusion test repeated 10 min after the preceding test exhibited a significant
      change in the characteristics of the ventricular fluid pressure (VFP) response
      but not in the epidural pressure (EDP) response. However, in the case of an
      infusion test which was repeated 2 h after the preceding test, it was observed
      that both the VFP and EDP responses remained the same as those found in the first
      infusion test.

PMID- 1979849
TI  - Actions of sex steroids and corticosteroids on rabbit choroid plexus as shown by
      changes in transport capacity and rate of cerebrospinal fluid formation.
AB  - The effect of betamethasone on choroid plexus transport and CSF formation in
      rabbits was studied. Following 5 days of daily treatment with betamethasone the
      CSF production rate was reduced by 43% as measured by ventriculo-cisternal
      perfusion with radioactive inulin. Accordingly, the Na(+)-K(+)-ATPase activity
      and the transport capacity in the choroid plexus, measured in terms of choline
      (10(-5) M) uptake and accumulation in vitro, decreased (in the lateral ventricles
      by 31% in both cases). Isolated choroid plexuses from rabbits were also used to
      determine uptake and accumulation of choline and the activities of various types
      of ATPases following pretreatment of the animals with 17-beta-oestradiol, alone
      or in combination with progesterone. The combined treatment reduced the choline
      uptake by 35% and also lowered the activity of Na(+)-K(+)-ATPase by 31% without
      influencing tissue wet weight. Thus, the demonstrated influences of
      glucocorticoids and sex steroids on the transport capacity in the choroid plexus
      seem to be important components in their postulated effects on intracranial
      hypertension.

PMID- 1979850
TI  - Influence of biological factors on changes in mean cerebral blood flow velocity
      in normal ageing: a transcranial Doppler study.
AB  - Analysis of the blood flow velocities in the middle cerebral artery by
      transcranial Doppler ultrasonography was performed in 158 healthy volunteers
      (aged 14-70 years; 82 men and 76 women). In a subgroup of 38 men and 21 women the
      end-tidal [CO2] was also measured. The influence of biological factors such as
      age, sex, end-tidal [CO2], and pulsatility and resistance indices on the mean
      blood flow velocity in normal ageing was investigated by multiple regression
      analysis. In both sex groups the measured mean blood flow velocity decreased
      significantly with age (P values less than 0.0003 for women and less than 0.0001
      for men). Women had significantly higher blood flow velocities than men (P =
      0.008) and the age-corrected sex difference of 5.2 cm s-1 did not significantly
      depend on age (P = 0.93). The age-related linear decline of the mean blood flow
      velocity could not be explained by a concomitant decrease of the end-tidal [CO2].
      In a group of subjects older than 50 years, the decrease of the mean blood flow
      velocity was significantly related to the increase of the pulsatility or
      resistance index.

PMID- 1979851
TI  - Glutamate- and aspartate-induced extracellular potassium and calcium shifts and
      their relation to those of kainate, quisqualate and N-methyl-D-aspartate in the
      isolated turtle cerebellum.
AB  - Ion-selective microelectrodes can be used to evaluate the characteristics and
      laminar distribution of excitatory amino acid agonist-induced K+ and Ca2+ shifts
      in the extracellular environment of brain cells. This report describes the
      pattern of K+ increases and Ca2+ decreases elicited by glutamate and aspartate at
      100 microns intervals in the isolated turtle cerebellum. These responses were
      compared to ion shifts evoked by kainate, quisqualate and N-methyl-D-aspartate.
      Glutamate and aspartate produced indistinguishable laminar patterns of ion
      shifts, with the greatest [K+]o and [Ca2+]o shifts in the granular layer. The
      average maximum granular and molecular layer increases in [K+]o were,
      respectively, 130% and 24% larger than the increase in the Purkinje cell layer.
      Kainate-induced increases in [K+]o also followed this granular greater than
      molecular greater than Purkinje cell layer pattern; however, the corresponding
      [Ca2+]o decreases were smaller and more variable. Quisqualate-evoked ion shifts
      in the molecular layer closely mimicked the shape of glutamate- and aspartate
      induced responses. In the granular layer, however, quisqualate caused little ion
      change during iontophoresis followed by large [K+]o and [Ca+]o shifts after the
      end of the pulse. The minimal ion shifts induced during quisqualate application
      in the granular layer gave this agonist the distinction of being the only agent
      tested to have its greatest direct effect in the molecular layer. N-Methyl-D
      aspartate caused large, two-phase [K+]o and [Ca2+]o shifts in the granular layer,
      only small [K+]o rises in the Purkinje cell and ventral molecular layers, and no
      response in the dorsal molecular layer. The lack of similarity between glutamate-
      and aspartate-induced ion shifts in the granular layer and those of any one
      agonist demonstrate the mixed agonist action of glutamate and aspartate in the
      cerebellum. These studies provide new information about the dynamics of
      excitatory amino acid receptor activation that is complementary to
      autoradiographic receptor mapping data and to single cell electrophysiological
      studies.

PMID- 1979852
TI  - Autoradiographic characterization of putative excitatory amino acid transport
      sites.
AB  - Removal of excitatory amino acids from the extracellular space is now postulated
      to occur through at least two distinct transport systems that are distinguished
      by their ionic dependency. Thus, both sodium-dependent and chloride-dependent
      systems have been described in the mammalian central nervous system. In this
      report we attempt to characterize these sites by autoradiography, using D
      [3H]aspartate and L-[3H]glutamate as ligands. Previous studies have shown that
      sequestration of radioligand into membrane vesicles can be a potential artifact
      when examining transport sites. We have found that sequestration can be
      alleviated by incubation of tissue sections in xylenes prior to incubation with
      radioligand. Using in vitro autoradiography we have characterized the two binding
      sites with respect to their distribution, kinetics and pharmacology. Both
      appeared to have a single, saturable binding site with Kds in the low micromolar
      range. Sodium-dependent D-aspartate binding predominated, having a Bmax that was
      five times greater than chloride-dependent L-glutamate binding in whole brain.
      The levels of binding to the two sites varied between brain regions. Sodium
      dependent D-aspartate binding was highest in the cerebellar molecular layer
      greater than dentate gyrus molecular layer greater than entorhinal cortex.
      Chloride-dependent L-glutamate binding was highest in the outer layers of
      cerebral cortex greater than dentate gyrus molecular layer greater than
      entorhinal cortex greater than striatum. Pharmacological characterization of
      these sites also showed major differences. Sodium-dependent D-aspartate binding
      was most potently inhibited by L-aspartate greater than threo-beta
      hydroxyaspartate greater than L-cysteine sulfinic acid greater than L-cysteic
      acid. Chloride-dependent glutamate binding was most potently inhibited by L
      glutamate greater than L-alpha-amino adipic acid greater than quisqualate greater
      than L-serine-o-sulfate. The differences in distribution, ligand binding
      properties and pharmacology of these sites suggest that a significant variable in
      excitatory amino acid circuitry may include heterogeneity in transporters
      associated with excitatory pathways.

PMID- 1979853
TI  - Somatostatin-14 and somatostatin-28 inhibit calcium currents in rat neocortical
      neurons.
AB  - The prosomatostatin-derived peptides, somatostatin-14 and somatostatin-28, are
      believed to function as neurotransmitters or neuromodulators in the cerebral
      cortex. To investigate the molecular mechanisms by which these peptides induce
      their physiological effects in the cerebral cortex, we have examined the effects
      of somatostatin-14 and somatostatin-28 on voltage-dependent Ca2+ currents in rat
      neocortical neurons in culture. Ca2+ currents were recorded using whole-cell
      patch-clamp techniques under conditions in which K+ and Na+ currents were
      blocked. Ca2+ currents were induced by depolarization from the holding potential
      of -80 mV. Somatostatin-14 (100 nM) and somatostatin-28 (100 nM) did not
      significantly affect low-voltage activated Ca2+ currents, but blocked high
      voltage activated Ca2+ currents and slowed the activation of this current. The
      effects of both peptides were concentration-dependent and reversible.
      Furthermore, the effects of somatostatin-14 and somatostatin-28 on the high
      voltage activated Ca2+ currents were not additive, suggesting that both peptides
      regulate this ionic current through similar cellular mechanisms. When patch
      pipettes used to record the Ca2+ currents contained 100 microM cAMP and 0.5 mM
      isobutylmethylxanthine, a phosphodiesterase inhibitor, somatostatin-14 and
      somatostatin-28 still inhibited Ca2+ currents, indicating that the effects of
      these peptides on the Ca2+ currents were cAMP-independent. Inclusion of the non
      hydrolysable guanine triphosphate analogue, guanine triphos-somatostatin-14 or
      somatostatin-28, suggesting the involvement of guanine nucleotide binding
      proteins in the actions of the peptides on the Ca2+ currents.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1979854
TI  - Anatomy of somatostatin-immunoreactive fibres and cell bodies in the rat
      trigeminal subnucleus caudalis.
AB  - The distribution of somatostatin-immunoreactive fibres and cells has been
      analysed in the rat spinal trigeminal subnucleus caudalis. Immunoreactive fibres
      are most concentrated in lamina II outer but fibres and terminals occur also in
      lamina I, lamina II inner, and scattered in the magnocellular region and
      neighbouring lateral reticular area. Immunoreactive cells occur in laminae I and
      II and in the magnocellular region of the nucleus but are most abundant in lamina
      II inner. The lamina II immunoreactive cells are morphologically heterogeneous
      and include types which are similar to cells described in Golgi studies such as
      stalked and islet cells. In order to distinguish somatostatin-immunoreactive
      primary afferents from intrinsic sources of somatostatin such as the lamina II
      neurons, we have used a monoclonal antibody (LD2) which is specific for primary
      afferents. Using dual-colour immunofluorescence we have shown that all
      somatostatin-immunoreactive cells in the trigeminal ganglia express LD2
      immunoreactivity. Quantitative immunostaining density profiles indicate that LD2-
      and somatostatin-immunoreactive fibres overlap mainly in lamina II outer and dual
      colour immunofluorescence confirms that this region contains somatostatin and LD2
      double-labelled fibres. In contrast, lamina I contains more somatostatin- than
      LD2-immunoreactive fibres and fewer double-labelled fibres. The presence of
      double-labelled fibres in outer lamina II indicates that somatostatin
      immunoreactive primary afferents terminate largely in this sublamina. However,
      the small number of double-labelled fibres found suggests that somatostatin
      immunoreactive fibres in laminae I and II are derived mainly from intrinsic
      sources such as the various types of lamina II neurons.

PMID- 1979855
TI  - Dopaminergic cells align along radial glia in the developing mesencephalon of the
      rat.
AB  - Studies were performed to examine the relation of dopaminergic cells and radial
      glia in the developing mesencephalon of the rat at ages E12-E20. Dopaminergic
      cells were immunolabelled with an antiserum which recognizes tyrosine
      hydroxylase, and radial glia were immunolabelled with a monoclonal antibody which
      recognizes vimentin. The vimentin-immunoreactive fibres of radial glia were noted
      at E12. At E12, and more clearly at later time points, the radial glia extended
      from the aqueduct to the pial surface, and this pattern persisted throughout the
      prenatal period. Tyrosine hydroxylase-immunoreactive cells were located along the
      ventral surface of the mesencephalon at age E13. At age E15, E16, and E18 the
      tyrosine hydroxylase-immunoreactive cells were present from the aqueduct to the
      ventral pial surface of the mesencephalon and were aligned along radial glia. Our
      study suggests that radial glia provide paths for migration of dopaminergic cells
      in the mantle layer from E15 to E18 of the developing mesencephalon. It also
      suggests that some dopaminergic cells between E15 and E18 may express tyrosine
      hydroxylase during their migration through the mantle layer and prior to reaching
      the location they occupy in the adult brain.

PMID- 1979857
TI  - Cosmid walking and chromosome jumping in the region of PKD1 reveal a locus
      duplication and three CpG islands.
AB  - The locus responsible for the most common form of autosomal dominant polycystic
      kidney disease (PKD1) is located on chromosome 16p13.3. Genetic mapping studies
      indicate that PKD1 is flanked on the proximal side by the DNA marker 26.6
      (D16S125). Here we show that 26.6 has undergone a locus duplication and that the
      two loci are less than 150kb apart. One of the two loci contains a polymorphic
      TaqI site that has been used in genetic studies and represents the proximal
      boundary for the PKD1 locus. We demonstrate that the polymorphic locus is the
      more proximal of the two 26.6-hybridizing loci. Therefore, four cosmids isolated
      from the distal 26.6-hybridizing locus contain candidate sequences for the PKD1
      gene. These cosmids were found to contain two CpG islands that are likely markers
      for transcribed regions. A third CpG island was detected and cloned by
      directional chromosome jumping.

PMID- 1979856
TI  - Genomic analysis of the major bovine milk protein genes.
AB  - The genomic arrangement of the major bovine milk protein genes has been
      determined using a combination of physical mapping techniques. The major milk
      proteins consist of the four caseins, alpha s1 (CASAS1), alpha s2 (CASAS2), beta
      (CASB), and kappa (CASK), as well as the two major whey proteins, alpha
      lactalbumin (LALBA) and beta-lactoglobulin (LGB). A panel of bovine X hamster
      hybrid somatic cells analyzed for the presence or absence of bovine specific
      restriction fragments revealed the genes coding for the major milk proteins to
      reside on three chromosomes. The four caseins were assigned to syntenic group U15
      and localized to bovine chromosome 6 at q31-33 by in situ hybridization. LALBA
      segregated with syntenic group U3, while LGB segregated with U16. Pulsed-field
      gel electrophoresis confirmed genetic mapping results indicating tight linkage of
      the casein genes. The four genes reside on less than 200 kb of DNA in the order
      CASAS1-CASB-CASAS2-CASK. Multiple restriction fragment length polymorphisms were
      also found at the six loci in three breeds of cattle.

PMID- 1979859
TI  - A HindIII polymorphism in the human NCF2 gene.

PMID- 1979858
TI  - cDNA and deduced amino acid sequence of rat liver prehsp60 (chaperonin-60).

PMID- 1979861
TI  - PstI and RsaI RFLPs in complete linkage disequilibrium at the CYP2E gene.

PMID- 1979860
TI  - An SspI RFLP at the D13S25 locus identified by the anonymous single copy probe H2
      42.

PMID- 1979862
TI  - A SacI RFLP of the human T-cell receptor delta (TCRD) joining segment J2.

PMID- 1979863
TI  - DdeI polymorphism in the HLA-DRA regulatory region.

PMID- 1979864
TI  - BcII RFLP of the plasminogen activator inhibitor type 2 gene (PLANH) on
      chromosome 18q21-q23.

PMID- 1979865
TI  - EcoRV polymorphism detected by cDNA probe for human tryptase beta (TPS2)
      [corrected].

PMID- 1979866
TI  - Isolation of a polymorphic DNA sequence YM44 (D2S78) on chromosome 2.

PMID- 1979867
TI  - An additional NsiI RFLP at the X-linked chronic granulomatous disease (CYBB)
      locus.

PMID- 1979868
TI  - D7S449 detects a HindIII polymorphism tightly linked to the MET gene on
      chromosome 7.

PMID- 1979869
TI  - Prostacyclin and EDRF Symposium. X Congress of the Polish Pharmacological
      Society. Bialystok, September 6-9, 1989. Proceedings.

PMID- 1979871
TI  - Health policy. Proceedings of an international conference. Jerusalem, Israel,
      June 6-19, 1987.

PMID- 1979870
TI  - Cross-tolerance to L-arginine-dependent guanylate cyclase activators in nitrate
      tolerant LLC-PK1 kidney epithelial cells.
AB  - Recently, it was shown that in LLC-PK1 kidney epithelial cells hormones such as
      vasopressin or oxytocin increase cyclic GMP in a receptor-mediated and L-arginine
      dependent manner. In the present study, the possible existence of cross-tolerance
      to vasopressin and oxytocin was investigated in nitrate-tolerant LLC-PK1 cells.
      Pretreatment with 1 mM glyceryl trinitrate for 3 h decreased cyclic GMP
      stimulation by 1 microM vasopressin and 1 microM oxytocin by 49% and 54%,
      respectively. Under the same conditions, cyclic GMP stimulation at 1 microM
      sodium nitroprusside was diminished by 56% whereas the cyclic GMP response to 100
      microM glyceryl trinitrate was virtually abolished. Our results demonstrate that
      a substantial degree of cross-tolerance to L-arginine-dependent guanylate cyclase
      activators occurs in nitrate-pretreated nonvascular cells which may be due to
      glyceryl trinitrate-induced desensitization of soluble guanylate cyclase.

PMID- 1979872
TI  - Transgene-induced mutation of the murine steel locus.
AB  - The product of the steel locus is essential for normal development of three
      distinct populations of stem cells--the neural crest-derived melanoblasts, germ
      cells, and blood cell precursors. Many mutant alleles at steel are lethal in
      homozygotes and produce coat color dilution in heterozygotes. We have identified
      a transgenic mouse with diluted pigmentation that closely resembles that of steel
      heterozygotes. We have demonstrated that the site of transgene insertion is
      genetically linked to the phenylalanine hydroxylase locus on mouse chromosome 10.
      In addition, the chromosome carrying the transgene fails to complement the
      recessive lethality of the Sl allele of steel and the pigmentation defect of the
      Slpan allele. The data indicate that the inserted transgene has disrupted the
      steel locus. The resulting allele, designated Sltg, provides a molecular tag for
      isolation of the steel gene, as well as a new allele for characterization of this
      developmentally important locus.

PMID- 1979873
TI  - In vitro effect of delta 9-tetrahydrocannabinol to stimulate somatostatin release
      and block that of luteinizing hormone-releasing hormone by suppression of the
      release of prostaglandin E2.
AB  - Previous in vivo studies have shown that delta 9-tetrahydrocannabinol (THC), the
      principal active ingredient in marijuana, can suppress both luteinizing hormone
      (LH) and growth hormone (GH) secretion after its injection into the third
      ventricle of conscious male rats. The present studies were designed to determine
      the mechanism of these effects. Various doses of THC were incubated with either
      stalk median eminence fragments (MEs) or mediobasal hypothalamic (MBH) fragments
      in vitro. Although THC (10 nM) did not alter basal release of LH-releasing
      hormone (LHRH) from MEs in vitro, it completely blocked the stimulatory action of
      dopamine or norepinephrine on LHRH release. The effective doses to block LHRH
      release were associated with a blockade of synthesis and release of prostaglandin
      E2 (PGE2) from MBH in vitro. In contrast to the suppressive effect of THC on LHRH
      release, somatostatin release from MEs was enhanced in a dose-related manner with
      a minimal effective dose of 1 nM. Since PGE2 suppresses somatostatin release,
      this enhancement may also be related to the suppressive effect of THC on PGE2
      synthesis and release. We speculate that these actions are mediated by the
      recently discovered THC receptors in the tissue. The results indicate that the
      suppressive effect of THC on LH release is mediated by a blockade of LHRH
      release, whereas the suppressive effect of the compound on growth hormone release
      is mediated, at least in part, by a stimulation of somatostatin release.

PMID- 1979874
TI  - Cross-linked A alpha.gamma chain hybrids serve as unique markers for fibrinogen
      polymerized by tissue transglutaminase.
AB  - Notwithstanding the high degree of amino acid sequence homologies between human
      factor XIIIa on the one hand and intracellular transglutaminases (protein
      glutamine:amine gamma-glutamyltransferase, EC 2.3.2.13) from guinea pig liver or
      human erythrocytes on the other, we find that the two sets of enzymes differ
      remarkably in the mode of cross-linking the same protein substrate--i.e., human
      fibrinogen. In the program of polymerization with factor XIIIa, production of the
      known gamma-gamma' homologous chain pairs is the dominant feature, whereas with
      either intracellular transglutaminase, a series of hitherto unidentified A
      alpha.gamma hybrid chain combinations, designated A alpha p gamma q (p and q = 1,
      2, 3...), is generated and practically no gamma-gamma' dimers are formed. Two
      dimensional electrophoresis is particularly useful for demonstrating the
      production of A alpha p gamma q structures by protein staining as well as by
      immunoblotting against specific antibodies to the A alpha and gamma chains of
      fibrinogen. These findings should aid in deciding whether the direct cross
      linking of fibrinogen by transglutaminase might contribute to thrombotic
      processes in addition to the thrombin- and factor XIIIa-dependent pathway of clot
      formation.

PMID- 1979875
TI  - Susceptibility or resistance to lysis by alloreactive natural killer cells is
      governed by a gene in the human major histocompatibility complex between BF and
      HLA-B.
AB  - The specificity recognized on normal allogeneic cells by a given alloreactive (1
      anti-A) natural killer clone is controlled by a gene locus termed EC1. Because
      the EC1 locus was previously shown to be located on chromosome 6, families
      characterized by a recombinant major histocompatibility complex haplotype were
      analyzed to map this locus more precisely. The breakpoint of recombination was
      studied by standard HLA typing, complement typing, and restriction fragment
      length polymorphism analysis of a series of genes located between the complement
      cluster genes and HLA-B within the major histocompatibility complex region. Three
      of 10 families analyzed were informative. From the data obtained, the EC1 locus
      maps between BF and HLA-B and presumably is one of the normal genes recently
      described in this region.

PMID- 1979876
TI  - The actions of diazepam and serotonergic anxiolytics vary according to the gender
      and the estrous cycle phase.
AB  - The anxiolytic effect of diazepam (0.5, 1.0 and 2.0 mg/kg), buspirone (2.5 and
      5.0 mg/kg), indorenate (2.5 and 5.0 mg/kg) and ipsapirone (5.0 and 10.0 mg/kg)
      was evaluated in male and female rats during the proestrus and metestrus phases.
      The burying behavior test was used to measure the anxiety levels. In this test,
      increases in the behavior latency are interpreted as prolonged reactivity, while
      reductions in the burying behavior are considered to reflect anxiolytic states.
      Diazepam increases in burying behavior latency were consistently higher than
      those observed after serotonergic anxiolytics. Buspirone, at no dose tested,
      affected the burying behavior latency, while indorenate and ipsapirone had only
      minor effects. Male individuals were more sensitive than females to the actions
      of diazepam on burying behavior. The serotonergic anxiolytics produce similar
      responses in both sexes. Metestrus females were much less sensitive to the action
      of all anxiolytics on burying behavior latency than proestrus females. Proestrus
      females were highly sensitive to the actions of diazepam on burying latency as
      compared both with males and metestrus females. Data show that a larger gender
      and within females variation occurs after treatment with diazepam as compared
      with the serotonergic anxiolytics. The results are discussed considering the
      relationships between ovarian hormones and the GABA-benzodiazepinic and
      serotonergic systems.

PMID- 1979877
TI  - Behavioural actions of the serotonergic anxiolytic indorenate.
AB  - Several recent studies have shown that the 5-HT1A agonist indorenate possesses
      antianxiety properties. In the present study we report on other behavioural
      actions of this drug. Indorenate (31.6 mg/kg) induced flat body posture, forepaw
      treading and hind limb abduction, behavioural characteristics of the serotonin
      syndrome. After indorenate injection these same behaviours were observed in
      animals pretreated with p-chlorophenylalanine (400 mg/kg X 3 days), suggesting
      that the action of this compound is not mediated via serotonin release. The beta
      5-HT1 blockers, (-) pindolol (2 mg/kg) or (-) alprenolol (5 mg/kg), did not
      prevent the actions of indorenate on the serotonin syndrome. Indorenate (10
      mg/kg) stimulated the masculine sexual behaviour by reducing the number of
      intromissions preceding ejaculation. Higher doses (17.8 mg/kg) cause a complete
      inhibition of sexual behaviour. (-) Pindolol (2 mg/kg) or (-) alprenolol (5
      mg/kg) did not antagonize the facilitatory actions of indorenate on male sexual
      behaviour. A high dose of indorenate (31.6 mg/kg) resulted in an impairment of
      the motor coordination as tested in a treadmill apparatus. These data reveal that
      indorenate possesses, in addition to its antianxiety effects, other behavioural
      characteristics that, however, appear at higher dose levels.

PMID- 1979878
TI  - Effect of melanotropin release inhibiting factor on changes by haloperidol and
      centbutindole in cerebral cortical 5-hydroxytryptamine receptors.
AB  - The effect of melanotropin release inhibiting factor (Pro-Leu-Gly-NH2, MIF) was
      determined on changes induced by two neuroleptics, haloperidol and centbutindole,
      in cerebral cortical 5-hydroxytryptamine (5-HT) receptors. Male Sprague-Dawley
      rats were injected daily i.p. with vehicle, haloperidol (1.0 mg/kg) or
      centbutindole (0.5 mg/kg), respectively, for 21 days. On day 22, these 3 groups
      were further divided into 2 subgroups and injected with either vehicle or MIF
      (2.0 mg/kg, i.p.) daily for 3 days. 3H-5-HT was used to study 5-HT1 receptors,
      and 3H-spiroperidol to label 5-HT2 receptors in the cerebral cortex. Chronic
      administration of haloperidol significantly increased (39.7%) the maximal binding
      capacity (Bmax) of 3H-5-HT binding to 5-HT1 receptors. Dissociation constant (Kd)
      values did not change. Centbutindole had no effect on 5-HT1 receptors. MIF had no
      effect on 5-HT1 receptors, nor did it alter haloperidol-induced increases in the
      Bmax of 3H-5-HT binding to 5-HT1 receptors. Chronic administration of
      centbutindole significantly increased (61.1%) the Bmax of 3H-spiroperidol binding
      to 5-HT2 receptors. No change occurred in the Kd values. Chronic treatment with
      haloperidol had no effect on 5-HT2 receptor characteristics. MIF had no effect on
      5-HT2 receptors or on the increase in 5-HT2 receptor density induced by
      centbutindole. The behavioral syndrome induced by 5-hydroxytryptophan (5-HTP)
      (50, 100 and 200 mg/kg, i.p.) was also measured in rats treated chronically with
      haloperidol or centbutindole. Haloperidol had no effect on the 5-HTP syndrome,
      whereas centbutindole stimulated by 24-45% the intensity of the
      syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1979879
TI  - Modelling soil productivity and pollution.
AB  - Predictive models of soil and plant processes should be of much benefit both in
      developing and developed countries. They can assist in enabling agronomic
      practices to be better adjusted for differences in conditions; in avoiding
      disasters that can accompany change in land use; in minimizing waste and
      environmental pollution, and in modifying and implementing legislation. These
      views are discussed in the light of recent advances. Particular attention is
      drawn to (i) the excellent relationships linking average national yields,
      nutrient uptakes, etc. to single factors such as average fertilizer application;
      (ii) equations for predicting the behaviour of added chemicals and water in soil
      that have been obtained by rigorous deduction from physical and chemical laws;
      (iii) the discovery of semi-empirical, but nevertheless widely applicable
      quantitative relations for key soil and plant processes, and (iv) the formulation
      and use of computer models for field situations. There is a pressing need to find
      ways of presenting the outcome of this work so that it can be more widely applied
      in practice.

PMID- 1979880
TI  - Modelling of microbial processes that govern degradation of organic substrates in
      soil, with special reference to pesticides.
AB  - We tried to develop deterministic models for kinetics of 2,4-D breakdown in the
      soil based on the following considerations: (i) at low concentrations degradation
      results from maintenance consumption by a large fraction of the soil microbial
      population; (ii) at high concentration in addition to the maintenance consumption
      there is a growth-associated carbon incorporation by a small specific microbial
      population. Values for the biokinetic parameters are consistent with those
      commonly found in the literature. Comparison between observed and simulated
      curves suggests that a non-negligible part of the pesticidal carbon exists as
      microbial by-products.

PMID- 1979881
TI  - Predicting the behaviour of pesticides in soil from their physical and chemical
      properties.
AB  - Increasingly stringent environmental requirements for pesticides mean that both
      biological activity and favourable environmental behaviour must be assessed at an
      early stage in pesticide discovery. Soil behaviour is governed by the physical
      properties of the molecule: partition coefficient, dissociation constant, vapour
      pressure and melting point, which control potential movement under particular
      soil and environmental conditions and the soil persistence. Established chemical
      structure-physical property correlations generally allow physical properties to
      be estimated for the large number of compounds in a synthesis programme with
      adequate precision. Stability to chemical or biological transformations in soil
      is more difficult to estimate but a combination of measurement for a few
      compounds and analogy with known chemical and biological transformation rates for
      various functional groups can give useful structure-stability correlations.

PMID- 1979883
TI  - [Horton's disease and Takayasu disease: an attempt at unification].

PMID- 1979882
TI  - The thermodynamics of bipolarity: a bifurcation model of bipolar illness and
      bipolar character and its psychotherapeutic applications.
AB  - Two models dominate current formulations of bipolar illness: the homeostatic
      model implicit in Freud's psychodynamics and most neuroamine deficit/excess
      theories; and the oscillatory model of exaggerated biological rhythms. The
      homeostatic model is based on the closed systems approach of classic
      thermodynamics, while the oscillatory model requires the open systems approach of
      modern thermodynamics. Here we present a thermodynamic model of bipolarity that
      includes both homeostatic and oscillatory features and adds the most important
      feature of open systems thermodynamics: the creation of novel structures in
      bifurcation processes. According to the proposed model, bipolarity is the result
      of exaggerated biological energy that augments homeostatic, oscillatory and
      creative psychological processes. Only low-energy closed systems tend to rest
      ("point attractor") and entropic disorder. Open processes containing and
      exchanging energy fluctuate between opposite states ("periodic attractors"); they
      are characteristic of most physiological rhythms and are exaggerated in bipolar
      subjects. At higher energies, their strong fluctuations destroy pre-existing
      patterns and structures, produce turbulence ("chaotic attractors"), which sudden
      switches between opposite states, and create new and more complex structures.
      Likewise, high-energy bipolars develop high spontaneity, great fluctuations
      between opposite moods, internal and interpersonal chaos, and enhanced creativity
      (personal, artistic, professional) as well as psychopathology (personality
      deviations, psychotic delusions). Offered here is a theoretical explanation of
      the dual--creative and destructive--nature of bipolarity in terms of the new
      enantiodromic concept of entropy generalized by process theory. Clinically, this
      article offers an integrative model of bipolarity that accounts for many clinical
      features and contributes to a definition of the bipolar personality.

PMID- 1979885
TI  - [Clinical significance of long-acting anti-anginal drugs in the treatment of
      cardiovascular diseases].

PMID- 1979884
TI  - Dexamethasone induction of gamma-glutamyl transferase in primary cultures of
      hepatocytes is enhanced by metyrapone.
AB  - Metyrapone, a cytochrome P-450 inhibitor, reduces by about 3,000 times the
      dexamethasone concentration required to cause a maximal induction of gamma
      glutamyltransferase in adult rat hepatocyte cultures, in itself having no
      inducing activity. Metyrapone effect decreases as dexamethasone concentration
      approaches the optimally inducing one. Metyrapone action on low DEX
      concentrations is dose-dependent while inhibiting 7-ethoxycoumarin O-deethylation
      by 20% to 75%. At the same doses, metyrapone amplifies also the effects of all
      the hormonal concentrations inducing tyrosine aminotransferase. These phenomena
      may be triggered by a modulation of the glucocorticoid biotransformation
      effective at both transcriptional and translational levels.

PMID- 1979886
TI  - Plantar fasciitis in runners. Treatment and prevention.
AB  - Plantar fasciitis is a common overuse injury found in runners. The plantar
      fascia, which is responsible for maintaining the integrity of the longitudinal
      arch, becomes irritated, inflamed or torn by repetitive stresses placed upon it.
      Commonly cited predisposers of plantar fasciitis are excessive pronation, a flat
      or cavus foot, tight Achilles tendon, type of training shoes worn, and errors in
      the training routine. Once the plantar fascia becomes irritated a myriad of
      conservative measures may be used, including everything from rest, ice and
      elevation to steroid injections and, if all else fails, surgery. In most cases
      conservative treatment of one kind or another will alleviate the symptoms of
      plantar fasciitis. However, it is essential to determine and correct the cause of
      the problem in order for the runner to resume normal activity levels. Controlling
      anatomical/biomechanical inefficiencies of the feet, stretching and strengthening
      exercises for the lower extremity, proper training shoes, and reasonable training
      routines will alleviate the symptoms of plantar fasciitis in a large percentage
      of sufferers. To prevent this injury, runners should be aware of the potential
      overuse injury and take precautionary measures, e.g. seek a
      biomechanical/anatomical evaluation from a qualified practitioner. The
      practitioner can then offer suggestions as to the specific steps the runner
      should follow to prevent the injury condition.

PMID- 1979887
TI  - [Angina pectoris--drug therapy and costs in a medical outpatient clinic in
      Switzerland].
AB  - Prescriptions and costs of pharmacotherapy for exertional angina pectoris were
      studied in males treated in 1975, 1980 or 1985 at the outpatient clinic of the
      university of Zurich. Monotherapy was increasingly replaced by two drug regimens
      (1975 43%, 1980 59%, 1985 35%) or by triple therapy (1975 2%, 1980 10%, 1985 28%)
      respectively. In 1985 beta-blocking agents and calcium antagonists were more
      frequently used instead of nitrates in monotherapy. In combined treatment
      modalities, nitrates associated with calcium antagonists or calcium antagonists
      combined with beta blockers were used increasingly in 1985. The most used
      substances in 1985 were isosorbide dinitrate, atenolol and nifedipine. In 1985
      nonselective beta blockers (propranolol, pindolol) were administered almost
      exclusively. The number of tablets administered per day decreased slightly over
      the years, while the doses of most commonly prescribed drugs increased. The cost
      per patient doubled during the observation period. Pharmacotherapy of stable
      angina calculated on the basis of 1985 pharmacy prices rose from 577 SFr. in 1975
      to 1180 SFr. in 1985.

PMID- 1979889
TI  - [Treatment of open fractures of the foot using external fixation].
AB  - The authors give an account of their experience with the use of compression-
      distraction for the treatment of open dislocation fractures of the foot. The
      device was designed by the authors and the results are satisfactory when the
      apparatus is used in the mentioned indications.

PMID- 1979890
TI  - [Cryptorchism in vicunas (Lama vicugna)].
AB  - In 1986 three cases of cryptorchidism were found in 60 vicugnas kept in
      zoological gardens. The castration of one male and the histology of the testicles
      are described. The importance of considering hereditary defects in breeding zoo
      animals is pointed out.

PMID- 1979888
TI  - Proceedings of the seventeenth congress of the Scandinavian Association of
      Urology. July 6-8, 1989, Reykjavik, Iceland. Abstracts.

PMID- 1979891
TI  - Widespread but variable toxicity in scleractinian corals.
AB  - Aqueous and/or aqueous ethanol extracts were made of 58 scleractinian species
      from 11 families, collected from Heron Island, Great Barrier Reef. At least one
      extract from each of 53 species (91%) exhibited activity against at least one
      bioassay system. Extracts from at least one colony of each of 41 species of the
      58 tested were toxic to mice when injected i.p. Cytolysis of sheep red blood
      cells was produced by extracts from at least one colony of each of 49 species of
      the 57 species tested and antibacterial activity was present in extracts from at
      least one colony of each of 37 species of the 55 tested. Only four species from
      45 species assayed yielded extracts toxic to mosquito fish. This is the first
      report of bioactivity in extracts of 46 species of coral and the first report of
      bioactivity of extracts of corals from the families Mussidae, Merulinidae,
      Siderastreidae, Oculinidae and Dendrophylliidae. Variable results on a particular
      bioassay exhibited by extracts from different colonies of a given species were
      analysed by the Generalized Linear Interactive Modelling system (GLIM). Toxicity
      to mice, cytolytic and antimicrobial activity are not significantly correlated
      with each other. No model could be generated to explain the variation in the
      incidence of cytolytic activity nor of antimicrobial activity. However
      antimicrobial activity varied significantly between collection trips and was
      negatively associated with the presence of immature gonads in the colonies. The
      model predicts that toxicity to mice will be higher in extracts collected when
      average maximum monthly air temperature is high.

PMID- 1979892
TI  - Intracolonial variation in toxicity in scleractinian corals.
AB  - Single colonies of the scleractinian corals Lobophyllia corymbosa, Favites
      abdita, Favia matthaii, Favia stelligera, Platygyra daedalea, Leptoria phrygia,
      Cyphastrea serailia, Hydnophora exesa and Astreopora myriophthalma were
      permanently marked with buoys on the reef flat at Heron Island. Great Barrier
      Reef. Portions of colonies were removed up to seven times at intervals of two or
      three months. Aqueous extracts of the colony portions were assayed using six
      bioassay regimes namely, toxicity to mice, toxicity to a coral and a hydroid,
      cytolytic activity on sheep erythrocytes and sea urchin ova and for antimicrobial
      activity on eight bacterial species. The incidence of one type of bioactivity in
      an extract was not correlated with the incidence of any other type of activity in
      that extract. Although each coral colony provided extracts that affected at least
      two of the bioassay systems, different activity profiles were obtained from
      successive extracts of each colony. Thus there is a temporal component to the
      idiosyncratic nature of bioactivity within a given colony of scleractinian coral.

PMID- 1979893
TI  - Restriction fragment-length polymorphism analysis of a second laboratory-derived
      mutant RT1 haplotype.

PMID- 1979894
TI  - Linkage between renin and fumarate hydratase genes in the rat.

PMID- 1979895
TI  - Screening for anti-human T-lymphotropic virus antibody in blood donors and
      polytransfused patients in Apulia (Italy).
AB  - A stringent procedure for the diagnosis of human T-lymphotropic virus (HTLV)
      infection was applied to 1,732 volunteer blood donors, 401 patients with various
      hematological disorders and 78 individuals at high risk for HIV infection. It
      consisted of a viral lysate-based screening assay (Abbott Laboratories, North
      Chicago, Ill., USA), and two confirmatory assays (Western blot and
      radioimmunoprecipitation assay). A confirmed positive sample had to react with at
      least two different HTLV gene products. Evidence of HTLV infection was not found
      in either blood donors or patients with hematological disorders. In fact, HTLV
      infection was only observed in 10 intravenous drug abusers or their sexual
      partners. Contrary to previous reports that claimed HTLV seroprevalences of
      between 0.3 and 8% in blood donors from Apulia (Italy), our data suggest that
      infection with this virus is principally restricted to intravenous drug abusers.

PMID- 1979897
TI  - [Use of autonomic drugs in disorders of the autonomic nervous system].

PMID- 1979896
TI  - [Molecular genetic studies in the von Willebrand's syndrome].
AB  - The successful cloning of the von Willebrand (vW) gene in 1985 and the production
      of gene probes stimulated a number of molecular genetic patient studies. It
      turned out that even in the case of patients with severe vW syndrome gross
      delections were only rarely found. We could not identify a deletion in the eight
      severe vW patients studied. Thus, at the moment it is not possible to directly
      demonstrate the genetic defect in vW patients. However, a number of restriction
      fragment length polymorphisms (RFLPs) within the vW gene were identified. They
      cosegregate with the gene and can be used for segregation analysis of the
      disease. These RFLPs should help to achieve better diagnosis of the vW syndrome
      in the future. This paper shows the data obtained in two families. They
      demonstrate the usefulness of RFLP analysis for diagnosis of carriers of the vW
      syndrome.

PMID- 1979898
TI  - Chemotaxis in Listeria monocytogenes.
AB  - Listeria monocytogenes is a flagellated bacterium with a characteristic tumbling
      motion. It is intriguing to speculate that directional motility might facilitate
      penetration of the intestinal epithelium or selective colonization of the central
      nervous system or gravid uterus. There are conflicting reports on the extent of
      flagellation and degree of motility at temperatures corresponding to the internal
      environment of the mammalian host. No studies of chemotaxis in Listeria have been
      reported. We examined Listeria for flagella, motility, and chemotaxis after
      growth at 10 degrees, 24 degrees, 30 degrees, 37 degrees and 40 degrees C.
      Listeria grown at all temperatures possessed flagella and were motile to at least
      some degree. Those grown at 24 degrees or 30 degrees C were the most abundantly
      flagellated and the most vigorously motile. The bacteria were able to swim
      towards tryptose at all temperatures and toward glucose at all temperatures
      except 40 degrees C.

PMID- 1979899
TI  - Restriction fragment length polymorphisms at the ornithine transcarbamylase locus
      in normal Chinese.
AB  - Ornithine transcarbamylase (OTC) (EC 2.1.3.3) is an hepatic mitochondrial enzyme
      involved in the detoxication of ammonia; it catalyzes the second step of the urea
      cycle, and is X-linked in human beings. Deficiency of OTC results in ammonia
      intoxication and, often, in early infant death, especially in males. This report
      describes the use of a nearly full-length cloned human cDNA for OTC for Southern
      blot analysis of genomic DNA. The pattern of MspI, TaqI, HindIII and EcoRI
      restriction endonuclease sites from 28 control individuals of Chinese backgrounds
      is reported. A Southern blot by Msp I reveals invariant bands of 19.5, 5.2 and
      1.9 kb respectively, as well as one set of polymorphic bands 6.6/6.2 kb. By TaqI,
      invariant bands are 4.8, 2.7, 1.9, 1.7 and 1.4 kb respectively, while polymorphic
      bands are found at 4.1/3.9 kb. By HindIII, 3.2 kb is invariant but 4.0/2.9 kb
      polymorphic. By EcoR I, invariant bands are 9.0, 3.6, 3.4 and 1.45 kb
      respectively, but 2.5 kb is polymorphic. Combined with study of the alteration of
      restriction sites in the informative pedigrees, this information is expected to
      allow accurate heterozygote detection and prenatal diagnosis of OTC deficiency.

PMID- 1979900
TI  - [Clinical evaluation of bunazosin hydrochloride for the treatment of voiding
      disturbances due to neurogenic bladder--a double-blind study].
AB  - The therapeutic utility of bunazosin hydrochloride was evaluated by a multi
      center (67 hospitals) double-blind controlled study in patients who complained of
      voiding disturbances due to neurogenic bladder. For means of comparison,
      bethanechol chloride and placebo were used as reference drugs. Bunazosin
      hydrochloride was orally administered 1.5 mg per day for the first week and 3.0
      mg per day for two weeks thereafter (Group E). Bethanechol chloride 15 mg (Group
      B) and placebo (Group P) were orally administered three times daily for three
      weeks. Three hundred and twenty-three cases were subjected to this study. The
      global improvement rating was analyzed for 244 cases (83 in Group E, 78 in Group
      B and 83 in Group P). The global utility rating (GUR) was analyzed for 252 cases
      (84 in Group E, 81 in Group B and 87 in Group P). Three hundred and twenty cases
      (107 in Group E, 104 in Group B and 109 in Group P) were analyzed with respect to
      overall safety rating (OSR). The global improvement ratings (excellent and good)
      were 32.5% in Group E, 28.2% in Group B and 21.2% in Group P. In the evaluation
      of GUR, Group E was superior to Group P. In addition, the incidence judged to be
      useless in Group E was significantly lower than that in Group B. There were no
      differences in OSR among these three groups. In the total evaluation of the
      subjective symptoms, the rates of improvement were not different among these
      three groups. In the total evaluation of the objective findings, the improvement
      rate in Group E was significantly higher than that in Group P. In addition, the
      deterioration rate in Group E was significantly lower than that in Group B. In
      objective findings before and after administration of bunazosin hydrochloride
      (Group E), the volume of residual urine, the rate of residual urine and the
      average flow rate improved significantly However, the bladder capacity, the
      maximum resting bladder pressure and the maximum urethral pressure did not change
      significantly. Bunazosin hydrochloride improved the objective findings regardless
      of the bladder capacity and the maximum resting bladder pressure. These
      significant improvements were marked in the neurogenic bladder patients who were
      able to urinate and in the patients whose urethral pressure was high. There were
      no differences in the incidence of side effects or in the appearance of abnormal
      values of laboratory findings in these three groups. Neither specific signs nor
      serious clinical side effects except those reported previously were
      observed.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1979902
TI  - [Stress on the coxal end of the femur during loading in the hip joint flexion
      posture].

PMID- 1979901
TI  - Dialysable nonspecific inhibitor of lymphocyte proliferation related to E
      receptors (CD2).
AB  - Several investigators have pointed out that lymphocytic function may be
      profoundly affected by soluble factors occurring in human serum. It was observed,
      previously, that the addition of normal human serum dialysate (NHSD), at the
      beginning of lymphocyte cultures, inhibited the proliferative response to
      phytohemagglutinin (PHA) and to allogeneic cells. This suppressive effect was
      removed by previous absorption of NHSD with sheep erythrocytes (E). These data
      suggested that the dialysable fraction of human serum contains a suppressive
      factor, apparently related to the human T cell receptor for E (T11 or CD2). In
      this study we investigated at which phase of the proliferative response does the
      inhibition induced by NHSD take place. In order to confirm the relationship
      between this inhibitory factor and E-receptors, the NHSD was subjected to passage
      through a sepharose affinity column sensitized with an anti-E-receptor serum.
      This anti-E-receptor serum was obtained by immunizing a sheep with autologous E
      sensitized with human E-receptors. Time-course experiments showed that NHSD
      inhibited lymphocyte proliferation induced by PHA even when added to the cultures
      18-24 h after mitogenic stimulation. In bidirectional mixed lymphocyte cultures
      the impairment of the proliferative response was inversely proportional to the
      time of NHSD addition. NHSD also inhibited the interleukin-2 (IL2) mediated
      proliferation of lymphoblasts previously exposed to PHA to ensure IL-2-receptors
      expression. The inhibitory effects of the NHSD were completely removed by
      absorption with E or by passing NHSD through the affinity column sensitized with
      the anti-E-receptor serum.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1979905
TI  - [VIIth International Congress of Parasitology. Paris, 20-24 August 1990.
      Proceedings].

PMID- 1979904
TI  - Trends in Cancer Mortality in Industrial Countries. Report of an international
      workshop. Capri, Italy, October 21-22, 1989. Proceedings.

PMID- 1979903
TI  - Neuroanatomic and neurochemical abnormalities in nonhuman primate infants exposed
      to weekly doses of ethanol during gestation.
AB  - Ethanol was orally administered once per week to 54 gravid pigtailed macaques
      (Macaca nemestrina) in doses of 0.0, 0.3, 0.6, 1.2, 1.8, 2.5 or 4.1 gm/kg from
      the 1st week in gestation or in doses of 2.5, 3.3 or 4.1 gm/kg from the 5th week.
      Mean maternal peak plasma ethanol concentrations (MPPEC's) ranged from 24 +/- 6
      mg/dl at the 0.3 g/kg dose to 549 +/- 71 mg/dl at the 4.1 g/kg dose. Thirty-three
      live born infants were assessed for abnormalities of physical and behavioral
      development. Ocular pathology, neuropathologic and neurochemical assessements
      were done on 31 animals at 6 months postnatal age. Microphthalmia was noted in
      three of the 26 animals exposed to ethanol. Retinal ganglion cell loss was
      significantly associated with intra-uterine ethanol exposure. Microphthalmia and
      retinal ganglion cell loss was observed in both the delayed and full-gestational
      exposed animals. No structural anomalies were found in the brains via gross
      inspection or light microscopy. Chemical abnormalities in the striatal nuclei
      were identified. Striatal dopamine concentrations increased with increasing MPPEC
      exposure (0-249 mg/dl) among animals exposed weekly to ethanol throughout
      gestation. Striatal dopamine concentrations decreased with increasing MPPEC
      exposure (260-540 mg/dl) among animals whose weekly exposure to ethanol was
      delayed until the 5th week of gestation. The same pattern of association was also
      noted between MPPEC and ultrastructural alterations in the caudate nucleus. The
      extent of ultrastructural alterations increased with increasing MPPEC among the
      full-gestational exposed animals and decreased with increasing MPPEC among the
      delayed-dose animals.

PMID- 1979906
TI  - [Miescher's granulomatous cheilitis. Diagnostic and therapeutic aspects].
AB  - Granulomatous cheilitis Miescher is a rare condition of unclear etiology, which
      is discussed as a monosymptomatic feature of Melkersson-Rosenthal-Syndrome, an
      extraintestinal form of Crohn's Disease or an unspecific cutaneous symptom of any
      granulomatous disease. Clinical appearance and diagnostic aspects are described.
      Therapeutical approaches as surgical intervention, corticoid- and sulfasalazine
      therapy and especially efforts with systemic clofazimine treatment are discussed.

PMID- 1979907
TI  - [Current concepts in the treatment of asthma (in the United States)].
AB  - The practice of medicine, in the United States, is regulated by different
      concepts when compared to France. Anti-asthmatic medications are very similar to
      the ones available in Western Europe, except the combinations (e.g.
      Berodual/Duovent), and the 200 mcg Beclomethasone MDls. Environmental control is
      emphasized, as well as a smoke-free environment. Immunotherapy is not
      recommended, although actively prescribed for generating income. For the last few
      years, American and French concepts -and problems-regarding asthma are coming
      closer.

PMID- 1979908
TI  - Takayasu's arteritis: a case report and discussion of differences in eastern and
      western cases.
AB  - The possibility of a different clinical expression of Takayasu arteritis (TA) in
      different geographic areas has been discussed in previous reports. However, many
      aspects of this problem still remain unclear. A very atypical case of TA
      concerning the early onset and the unusually slow progress of the disease is
      reported. Referring to anatomicopathological, clinical, and therapeutic
      prognostic criteria reported in literature from oriental countries, many
      discrepancies appear evident. This is consistent with the hypothesis of two
      different clinical varieties of TA and suggests that, both in its prepulseless
      stage and after its actual recognition, this disease could show a less malignant
      progress in western countries.

PMID- 1979909
TI  - Long-term use of benzodiazepines.

PMID- 1979910
TI  - Polyionic compounds selectively alter availability of CD4 receptors for HIV coat
      protein rgp120.
AB  - We studied the ability of several polyionic compounds, previously shown to have
      activity in vitro against human immunodeficiency virus (anti-HIV) to block
      binding of anti-CD4 and recombinant HIV gp120 to the CD4 receptor on human
      lymphocytes. We found that Evans blue and aurin tricarboxylic acid could
      completely inhibit binding of anti-CD4 (Leu3a) and rgp120 and have selectivity
      for the CD4 receptor. A number of other compounds, including dextran sulfate and
      heparin had no effect on binding of rgp120 and were shown to be nonspecific for
      inhibition of binding of monoclonal antibodies to different T-cell receptors.
      Studies using a number of membrane-active drugs showed that changes in membrane
      potential or ion fluxes were not involved in the inhibition of binding of rgp120
      by Evans blue or aurin tricarboxylic acid.

PMID- 1979911
TI  - The role of alpha 1-adrenoceptors in adrenaline-induced hyperkalaemia.
AB  - The hyperkalaemic action of adrenaline was investigated in 44 anaesthetized
      domestic pigs. Plasma and epicardial concentrations of K+ were measured, in the
      latter case with an ion-selective electrode. Adrenaline 10 micrograms kg-1 caused
      a rapid increase in the plasma concentration of K+ from 4.2 to 5.9 mmol litre-1.
      The magnitude and the time course of epicardial concentration of K+ were similar.
      Alpha-adrenoceptor block with either phentolamine 5 mg kg-1 (non-selective block)
      or prazosin 0.1 mg kg-1 (selective alpha 1-adrenoceptor block) abolished the
      hyperkalaemic effect of adrenaline in the plasma and on the epicardium. The alpha
      1-adrenoceptor agonist phenylephrine increased the K+ concentration, but the
      alpha 2-adrenoceptor agonist UK 14.304 did not cause any change in concentration.
      These results suggest that the hyperkalaemia induced by adrenaline occurs in the
      interstitial fluid of the myocardium and is mediated by alpha 1-adrenoceptors.
      These findings may be important in patients at risk of hyperkalaemia, with
      implications, for example, in the use of suxamethonium during induction of
      anaesthesia.

PMID- 1979912
TI  - Factor XIIIa in nodular malignant melanoma and Spitz naevi.
AB  - The distribution of factor XIIIa-positive dermal dendritic cells was studied in a
      series of nodular malignant melanomas and compared with that seen in Spitz naevi.
      Two patterns of distribution were recognizable: (a) diffusely spread through the
      tumour and (b) located mainly at the periphery of the tumour. These did not
      correlate with the diagnosis of melanoma or Spitz naevus and the distribution
      appeared to be a function of growth pattern of the tumour. The diffuse pattern
      was the most common regardless of diagnosis and the distribution of factor XIIIa
      positive cells is the same in malignant melanoma and Spitz naevi.

PMID- 1979913
TI  - CD4 and CD8 subpopulation changes during high dose intravenous immunoglobulin
      treatment.
AB  - High doses of immunoglobulin, when given intravenously (IVIgG), influence
      lymphocyte subset numbers and function. T-lymphocytes may be subdivided into two
      functionally different groups, helper/inducer (CD4+) and suppressor/cytotoxic
      (CD8+). Considerable functional as well as phenotypic heterogeneity exists within
      the two major subsets. CD4+ cells have been further subdivided into
      helper/inducer and suppressor/inducer sets by the differential binding of two
      monoclonal antibodies 4B4 (CDw29) and 2H4 (CD45R). Similarly, the CD8+ subset may
      be subdivided into suppressor and cytotoxic populations by the differential
      binding of monoclonal antibodies which identify the C3bi receptor (CD11). During
      IVIgG treatment of patients with autoimmune thrombocytopenic purpura (ATP) the
      change in CD4/CD8, due to an absolute increase in CD8+ cells, has been shown to
      correlate with the response to treatment as determined by platelet increase.
      However, the total CD4+ and CD8- numbers may not reflect changes in their
      constituent subpopulations. To examine this possibility the CD4 and CD8
      subpopulations were analysed in 15 ATP patients, during IVIgG treatment, using a
      double fluorescence technique. In 10 of these patients the in vitro response to
      pokeweed mitogen (PWM) and Staphylococcus aureus Cowan I (STA Cowan I) was
      determined. There was no correlation between the change in CD8+ subpopulations
      and response to treatment but there was a correlation between the CD4+ change and
      platelet increment. In addition there was a correlation between the 4B4/2H4
      change and the in vitro response to PWM but no correlation with the response to
      STA Cowan I. These findings suggest that during IVIgG treatment the CD4+ 4B4+
      helper/inducer population is influenced resulting in reduced T-dependent B-cell
      activation.

PMID- 1979914
TI  - c-erbB-2 protein expression in node negative breast cancer.
AB  - We investigated the expression of c-erB-2 protein in two matched groups of breast
      cancer patients, one with and one without relapse. 37 patients with relapse were
      compared with 42 patients without recurrence for time of observation, adjuvant
      treatment, age, menopausal status and estrogen receptor content. Paraffin
      embedded sections were stained with the polyclonal antibody 21N, raised against a
      synthetic peptide from the predicted sequence of the c-erbB-2 protein. The
      staining of c-erbB-2 was measured on a scale of 0 to 3+. C-erbB-2 staining was
      negative in 16 (38%) patients in the relapse-free group, and in 8 (22%) of the
      patients with metastases. Neither disease-free survival (DFS) nor overall
      survival (OS) were dependent upon the extent of c-erbB-2 expression. An analysis
      by estrogen receptor (ER) status (i.e. positive or negative) and by c-erbB-2
      expression (i.e. positive or negative) revealed that patients with ER-positive
      primaries and negative c-erbB-2 have the longest disease-free survival (DFS) and
      overall survival (OS). We conclude that c-erbB-2 expression might be clinically
      useful only if other prognostic variables (e.g. estrogen receptor content in the
      tumor) are also considered.

PMID- 1979916
TI  - Epidural sufentanil for TKR-respiratory depression?

PMID- 1979915
TI  - Toxicity of chronic spinal analgesia in a canine model: neuropathologic
      observations with dezocine lactate.
AB  - The chronic spinal toxicity of dezocine lactate was investigated in mongrel dogs.
      Dogs received chronic intrathecal infusion from implanted infusion pumps for 28
      136 days. Infusion of saline via intrathecal catheters produced leptomeningeal
      fibrosis, sometimes with spinal cord compression. Dezocine lactate infusion, in
      addition to similar leptomeningeal changes, was also associated with severe
      parenchymal lesions in all cases. The exact cause of this toxicity cannot be
      specifically assigned; potential contributing factors include catheter-induced
      reaction, pH of the drug, lactate concentration, osmolality and the pharmacologic
      agent itself. Leptomeningeal reaction in control dogs limits the value of chronic
      intrathecal dog models for assessment of spinal drug toxicity.

PMID- 1979918
TI  - Methylmalonyl-CoA mutase (EC 5.4.99.2) and methionine synthetase (EC 2.1.1.13) in
      the tissues of cobalt-vitamin B12 deficient sheep.
AB  - The changes in the activities of the two vitamin B12-dependent enzymes
      methylmalonyl-CoA mutase (EC 5.4.99.2) and methionine synthetase (5
      methyltetrahydrofolate-homocysteine methyltransferase, EC 2.1.1.13) are described
      in two groups of sheep maintained for 20 weeks on either a cobalt-deficient or a
      Co-sufficient whole-barley diet. At the end of that period, the plasma
      concentrations of vitamin B12 were depressed and those of methylmalonic acid were
      raised in the Co-deficient group. During the course of the experiment hepatic
      holo-mutase activity, measured on biopsy samples, declined in Co-deficient
      animals with a half-life of 73 d. There was a similar, but slower decline in
      lymphocyte holo-mutase activity which fell with a half-life of 125 d. At
      slaughter, there was no difference between Co-sufficient and Co-deficient animals
      in total mutase activity in liver, kidney, brain and spinal cord. In contrast,
      the total-synthetase activity of liver and kidney was reduced by 60 and 30%
      respectively in the Co-deficient animals. There was no change in either group of
      animals in total-synthetase activity, or in either holo-mutase or holo-synthetase
      activity, in brain and spinal cord. In the Co-deficient animals, holo-mutase and
      holo-synthetase activities in liver, the tissue with the greatest activity of
      both enzymes, fell to 25 and 39% respectively, of that of Co-sufficient animals.
      The corresponding reductions for kidney were 12 and 51% respectively. These
      results indicated that activity of both holoenzymes is greatly reduced in Co
      deficient sheep.

PMID- 1979917
TI  - Non-essential nitrogen and protein utilization in the growing rat.
AB  - Three series of nitrogen-balance experiments were carried out on growing rats fed
      on purified isonitrogenous diets (16 g N/kg) to study the importance of non
      essential N and the essential:total N (E:T) ratio for attaining maximum N balance
      (NB) and biological value (BV) of protein. Minimum dietary levels of asparagine,
      proline and glutamic acid required for maximum NB and BV were estimated to be
      1.0, 2.0 and 5.0 g/kg respectively. In an essential amino acid-based diet, the
      levels of individual amino acids were successively reduced to 110% of the
      requirement. Reducing the level of arginine, lysine or methionine + cystine
      resulted in a significant increase in NB and BV while the response of rats given
      the isoleucine-reduced diet significantly decreased. Addition of asparagine,
      proline and glutamic acid in the estimated minimum amounts to an essential amino
      acid-based diet resulted in a significant increase in NB and BV. A further
      significant increase was found when the levels of arginine, lysine and methionine
      + cystine in the diet were reduced to 110% of the requirement. The performance of
      rats fed on the latter diet was similar to that of rats given a diet with the
      optimum E:T ratio. It is concluded that the optimum protein utilization may be
      influenced by the presence of some non-essential amino acids and by the surplus
      of some essential amino acids rather than by the E:T ratio per se.

PMID- 1979919
TI  - Intestinal uptake of dipeptides and beta-lactam antibiotics. I. The intestinal
      uptake system for dipeptides and beta-lactam antibiotics is not part of a brush
      border membrane peptidase.
AB  - The uptake of beta-lactam antibiotics into small intestinal enterocytes occurs by
      the transport system for small peptides. The role of membrane-bound peptidases in
      the brush border membrane of enterocytes from rabbit and pig small intestine for
      the uptake of small peptides and beta-lactam antibiotics was investigated using
      brush border membrane vesicles. The enzymatic activity of aminopeptidase N was
      inhibited by beta-lactam antibiotics in a non-competitive manner whereas
      dipeptidylpeptidase IV was not affected. The peptidase inhibitor bestatin led to
      a strong competitive inhibition of aminopeptidase N whereas the uptake of
      cephalexin into brush border membrane vesicles was only slightly inhibited at
      high bestatin concentrations (greater than 1 mM). Modification of brush border
      membrane vesicles with the histidine-modifying reagent diethyl pyrocarbonate led
      to a strong irreversible inhibition of cephalexin uptake whereas the activity of
      aminopeptidase N remained unchanged. A modification of serine residues with
      diisopropyl fluorophosphate completely inactivated dipeptidylpeptidase IV whereas
      the transport activity for cephalexin and the enzymatic activity of
      aminopeptidase N were not influenced. With polyclonal antibodies raised against
      aminopeptidase N from pig renal microsomes the aminopeptidase N from solubilized
      brush border membranes from pig small intestine could be completely precipitated;
      the binding protein for beta-lactam antibiotics and oligopeptides of apparent Mr
      127,000 identified by direct photoaffinity labeling with [3H]benzylpenicillin
      showed no crossreactivity with the aminopeptidase N anti serum and was not
      precipitated by the anti serum. These results clearly demonstrate that peptidases
      of the brush border membrane like aminopeptidase N and dipeptidylpeptidase IV are
      not directly involved in the intestinal uptake process for small peptides and
      beta-lactam antibiotics and are not a constituent of this transport system. This
      suggests that a membrane protein of Mr 127,000 is (a part of) the uptake system
      for beta-lactam antibiotics and small peptides in the brush border membrane of
      small intestinal enterocytes.

PMID- 1979921
TI  - Evidence that isoproterenol-induced Ca2(+)-mobilization in rat parotid acinar
      cells is not mediated by activation of beta-adrenoceptors.
AB  - The effects of isoproterenol (ISO), a beta-adrenoceptor agonist, on cytosolic
      free Ca2+ ([Ca2+]i) in rat parotid acinar cells were examined using the
      fluorescent Ca2(+)-indicator fura-2. At concentrations up to 1 mM, ISO caused a
      rapid increase in [Ca2+]i in a dose-dependent manner, while addition of 1 microM
      ISO, which evokes the maximum amylase secretion, had only a slight effect on
      [Ca2+]i. There was no such increase in [Ca2+]i with the addition (2 mM) of 8
      bromo-cyclic AMP, a permeant cyclic AMP analogue. The alpha-adrenoceptor
      antagonist phentolamine blocked the ISO-induced [Ca2+]i increase better than the
      beta-adrenoceptor antagonist, propranol, and the muscarinic receptor antagonist,
      atropine. The IC50 value (the concentration which reduces the ISO-induced
      increase in [Ca2+]i by 50%) of phentolamine was estimated to be 7.6 nM, for
      propranolol 13.2 microM and for atropine 3.5 microM. The difference in potency
      between the three antagonists was similar to the difference in blocking the
      [Ca2+]i increase induced by phenylephrine, an alpha-adrenoceptor agonist. These
      results suggest that the Ca2(+)-mobilization in response to high concentrations
      of ISO results from an activation of alpha-adrenoceptors rather than beta
      adrenoceptors.

PMID- 1979920
TI  - Evidence for daunomycin efflux from multidrug-resistant 2780AD human ovarian
      carcinoma cells against a concentration gradient.
AB  - Using a flow-through system human multidrug-resistant 2780AD ovarian carcinoma
      cells were exposed to flowing culture medium containing the anticancer agent
      daunomycin (5 microM). A pulse of medium containing verapamil caused increased
      cellular daunomycin accumulation, resulting in a dip in the fluorescence signal
      from daunomycin in the effluent. After passage of this pulse we observed an
      efflux of more than 90% of this extra accumulated daunomycin within 10 min. This
      daunomycin efflux against a concentration gradient provides evidence for drug
      efflux from these cells being an active process. After the addition of
      methylamine to the medium to increase intravesicular pH, the dip in the
      fluorescence signal was not decreased, indicating that vesicular transport was
      not an important component of this efflux.

PMID- 1979922
TI  - Metabolic problems of the newborn. Proceedings of the IVth International
      Symposium on Neonatology: an update. Venice, March 29-31, 1990.

PMID- 1979923
TI  - Pharmacokinetics of pafenolol after i.v. and oral administration of three
      separate doses of different strength to man.
AB  - The pharmacokinetics of pafenolol were evaluated in 12 healthy subjects after
      administration of three single IV doses (5, 10, and 20 mg) and three oral single
      doses (25, 50, and 100 mg). The drug was discontinuously absorbed. A first peak
      was observed 0.5 to 1.5 h after dosing and a second higher maximum concentration
      was noted 3 to 5 h after the administration in the majority of the experiments.
      The mean systemic availability increased from 27 +/- 5 per cent for the oral 25
      mg dose to 46 +/- 5 per cent for the 100 mg dose, i.e., an increase of about 70
      per cent (p less than 0.05). The half-life of distribution varied between 5 and 6
      min and the apparent volume of distribution (Vz) was about 1.11 kg-1. The
      distribution was linear in the IV dose range studied. Total body clearance was
      about 300 ml min-1. About 50 per cent of the systemically available dose was
      excreted unchanged via the kidneys. Total body clearance decreased by about 13
      per cent (p less than 0.05) by increasing the dose from 5 to 20 mg IV possibly
      because of reduced renal elimination. Mean terminal t1/2 of the IV dose was
      approximately 3.5 h. The corresponding t1/2 of the oral dose was approximately 6
      h indicating absorption rate-limited kinetics of the oral dose.

PMID- 1979924
TI  - Pharmacokinetics of pafenolol in the rat: a suitable model for studying
      absorption mechanisms of a drug exhibiting unusual absorption properties in man.
AB  - The pharmacokinetics of pafenolol, a highly selective beta 1-adrenoceptor
      antagonist, have been studied in starved and unstarved rats. Separate groups
      received intravenous doses (0.3 and 3.0 mumol kg-1) and oral doses (1 and 25
      mumol kg-1). The systemic clearance of pafenolol was constant in the dose range
      investigated where the absolute oral bioavailability increased from 15 to 27 per
      cent in the starved and from 9.1 to 21 per cent in the unstarved rats, when the
      oral dose was raised from 1 to 25 mumol kg-1. The blood concentration profile
      after an oral solution of pafenolol exhibited two peaks in the majority of the
      rats. The major part of the absorption was associated with the second peak which
      appeared about 4 h after dosing in both starved and unstarved rats. Food lowered
      the degree of bioavailability and shifted the tmax1 to about 1 hour compared to
      half an hour in starved rats. The low bioavailability was primarily due to
      incomplete uptake from the gastrointestinal tract. Our study shows that pafenolol
      is absorbed in a similar way to that in man. The mechanisms behind the dose
      dependent bioavailability and the two peaks in the absorption profile after an
      oral solution will be further explained in the rat.

PMID- 1979925
TI  - Does restriction of caffeine intake affect mixed function oxidase activity and
      caffeine metabolism?

PMID- 1979926
TI  - Impaired transendothelial migration by neonatal neutrophils: abnormalities of Mac
      1 (CD11b/CD18)-dependent adherence reactions.
AB  - In order to evaluate the functions of lymphocyte function antigen-1 (LFA-1)
      (CD11a/CD18) and Mac-1 (CD11b/CD18) on neonatal neutrophils, we examined
      neutrophil adhesion to and migration through human umbilical vein endothelial
      cell (HUVEC) monolayers in vitro. Transendothelial migration of adult neutrophils
      was greatly enhanced by preincubation of HUVEC with interleukin-1 (IL-1). This
      migration was significantly inhibited by monoclonal antibodies (MoAbs) against
      LFA-1 (CD11a) and Mac-1 (CD11b) subunits. Migration of neonatal neutrophils was
      markedly diminished compared to adult neutrophils, and MoAbs against LFA-1
      further reduced migration. In contrast, anti-Mac-1 MoAb was not inhibitory.
      Adhesion of adult neutrophils was significantly enhanced by prestimulation of
      HUVEC with IL-1, and was significantly inhibited by MoAbs against LFA-1. Adhesion
      of neonatal neutrophils was near adult levels and comparably inhibited by anti
      LFA-1 MoAb. In addition, adhesion of neonatal and adult neutrophils to purified
      ICAM-1 in artificial planar membranes was comparable and almost completely
      inhibited by anti-LFA-1 MoAb. Chemotactic stimulation induced Mac-1-dependent
      adhesion of adult neutrophils to endothelial cells, purified intercellular
      adherence molecule-1 (ICAM-1) and protein-coated glass. In marked contrast,
      adhesion of neonatal neutrophils to these substrates was not significantly
      increased by chemotactic stimulation. These findings indicate that diminished
      transendothelial migration by neonatal neutrophils is related to abnormal
      interactions of Mac-1 with ICAM-1 and possibly other endothelial ligands. These
      functional deficits may contribute to impaired inflammation and infectious
      susceptibility in human neonates.

PMID- 1979927
TI  - Semen analysis in patients operated on for impalpable testes.
AB  - Semen analysis was performed on 48 men who had undergone orchiopexy, 40 for
      unilateral impalpable testes and 8 for bilateral impalpable testes. Patients with
      unilateral impalpable testes had varying sperm analysis; 18 (86%) of the 23
      patients with unilateral impalpable canalicular testes had normal sperm analysis.
      All patients with bilateral impalpable testes were azoospermic. The subsequent
      quality of the semen is dependent upon the original anatomical positions of the
      undescended testes.

PMID- 1979928
TI  - Light-microscopic localization of somatostatin binding sites in the locus
      coeruleus of the rat.
AB  - Somatostatin (SS14) binding sites within locus coeruleus (LC) were localized at
      the light microscope level by [125I][Tyr0,D-Trp8]SS14 radioautography combined
      with an immunohistochemical/neurotoxic lesioning approach. In intact rats, the
      dense accumulation of SS14 binding sites of LC conspicuously overlapped with the
      cluster of tyrosine hydroxylase (TH) immunoreactive neurons; SS14 specific
      binding was directly proportional to the number of TH immunostained (TH+) cell
      bodies per mg of tissue throughout LC. Complete lesion of catecholaminergic nerve
      cell bodies of LC by intracerebroventricular injection of 6-hydroxydopamine (6
      OHDA) resulted in the total abolition of SS14 specific binding in the structure.
      In addition, specifically bound [125I][Tyr0, D-Trp8]SS14 and TH+ cell density
      were quantified serially in a set of rats bearing various partial neurotoxic
      lesions; a highly significant correlation was found between the two parameters at
      each of the 16 coronal levels of LC examined. The coefficient of proportionality
      was identical at all levels. These results strongly suggest that somatostatin
      binding sites are uniformly localized on all noradrenergic neurons of LC.

PMID- 1979929
TI  - The epileptiform activity induced by 4-aminopyridine in rat amygdala slices:
      antagonism by non-N-methyl-D-aspartate receptor antagonists.
AB  - The effects of excitatory amino acid receptor antagonists kynuretic acid and 6
      cyano-7-nitroquinoxaline-2,3-dione (CNQX) on epileptiform activity induced by 4
      aminopyridine (4-AP) were studied in rat amygdala slices using intracellular
      recording techniques. Five to 10 min after switching to 4-AP-containing solution,
      spontaneous epileptiform bursts were observed in 35 out of 45 slices studied. The
      spontaneous epileptiform events consisted of an initial burst followed by a
      number of afterdischarges. Superfusion with kynuretic acid, a broad-spectrum
      excitatory amino acid receptor antagonist, reversibly reduced the duration of the
      spontaneous bursting discharges in a dose-dependent manner. The frequency of
      spontaneous bursting was also decreased. The IC50, estimated from the graph of
      the concentration-response relationship, was approximately 130 microM. In
      addition, CNQX which is a specific non-N-methyl-D-aspartate (NMDA) receptor
      antagonist blocked the spontaneous and evoked epileptiform bursting. In 11 out of
      15 neurons tested, there was a residual depolarizing component remained. This
      depolarizing component was reversibly blocked by specific NMDA receptor
      antagonist, D,L-2-amino-5-phosphonovaleate (D,L-APV). Relative to the CNQX
      sensitive component, the D,L-APV-sensitive component is much smaller in amplitude
      and shorter in duration indicating that NMDA receptor plays only a minor role in
      this process. These data suggest that the generation or propagation of
      spontaneous epileptiform events induced by 4-AP in the neurons of basolateral
      amygdala is mediated by excitatory amino acids and that activation of non-NMDA
      receptors is of primary importance.

PMID- 1979930
TI  - Analgesic synergy and improved motor function produced by combinations of mu
      delta- and mu-kappa-opioids.
AB  - This study evaluated the effects of intrathecal administration of a low-analgesic
      dose of the selective mu-agonist DAMGO co-administered with sequentially
      increasing doses of either the selective delta-agonist DPDPE or the selective
      kappa-agonist, U50,488H on mechanical nociceptive thresholds in the rat. Potent
      analgesic synergy was observed with both combinations. Since an elevation in
      nociceptive threshold can result from motor deficits, as well as true analgesia,
      we also evaluated the effects of the combination regimens on motor coordination
      using a rotarod apparatus. The combination regimens produced significantly less
      motor deficits than those observed when DPDPE and U50,488H were administered as
      single agents. These findings of enhanced analgesia with decreased motor side
      effects associated with administration of fixed mu/delta or mu/kappa combinations
      suggest that co-administration of opiates that act at different receptors may
      constitute a superior approach to the treatment of pain.

PMID- 1979931
TI  - Chronic benzodiazepine treatment and cortical responses to adenosine and GABA.
AB  - The effects of chronic treatment of mice with clonazepam have been examined on
      the responses of neocortical slices to adenosine, 5-hydroxytryptamine (5-HT) and
      gamma-aminobutyric acid (GABA). Responses to these agonists were measured as
      changes in the depolarisation induced by N-methyl-D-aspartate (NMDA). Added to
      the superfusion medium diazepam blocked responses to adenosine but not 5-HT; this
      effect was not observed with 2-chloroadenosine or in the presence of 2
      hydroxynitrobenzylthioguanosine. GABA was inactive in control slices but chronic
      treatment with clonazepam induced responses to GABA and enhanced responses to
      adenosine but not 5-HT. It is suggested that the induction of GABA responses may
      reflect the up-regulation of GABA receptors, but the increase of adenosine
      responses by clonazepam implies that there is no simple relationship between
      adenosine receptor binding and functional responses.

PMID- 1979932
TI  - The clinical relevance of multidrug resistance.

PMID- 1979933
TI  - Acute heart failure in intensive care: a new approach. Proceedings of a
      symposium. Cambridge (UK), July 1, 1989.

PMID- 1979934
TI  - Enoximone potentiates the positive inotropic effects of beta-1- and beta-2
      adrenoceptor stimulation in human atrial myocardium.
AB  - The aim of these studies was to determine whether phosphodiesterase inhibition by
      enoximone is able to regulate differentially beta 1- and beta 2-adrenoceptor (AR)
      mediated inotropic effects. Strips of human right atrial myocardium were
      stimulated with noradrenaline plus ICI 118,551 (selective beta 1-AR stimulation)
      or adrenaline plus CGP 20,712A (selective beta 2-AR stimulation). Concentration
      effect curves were determined in the absence or presence of enoximone. Enoximone
      alone was shown to produce dose-related positive inotropic effects. In tissues
      from beta 1-blocker-treated patients, enoximone potentiated the responses to both
      beta 1-AR and beta 2-AR stimulation. There was a fall in -log EC50 (mol/l) of 0.7
      +/- 0.2 (mean +/- SEM; n = 6) for beta 1-AR stimulation and of 0.6 +/- 0.1 (n =
      10) for beta 2-AR stimulation. The potentiation of beta 2-AR responses in non
      beta-blocker-treated patients was similar with a fall in -log EC50 (mol/l) of 0.5
      +/- 0.1 (n = 6). The extent of potentiation was not significantly different
      between beta 1-AR and beta 2-AR stimulation, nor between beta 1-blocker-treated
      patients and non-beta-blocker-treated patients. Further experiments showed that
      the potentiation by enoximone of the effects of catecholamines was unaltered by
      diazoxide (n = 6). Enoximone thus causes positive inotropic effects and
      potentiates the effects of catecholamines acting through both beta 1- and beta 2
      AR. These actions are consistent with inhibition of cyclic AMP hydrolysis. The
      potentiation of the effects of catecholamines by phosphodiesterase inhibition
      appears unaltered by prior patient therapy with beta 1 blockers.

PMID- 1979935
TI  - Evaluation of the effect of dietary thiram on gamma-glutamyltranspeptidase
      activity and histopathology of pancreas of rats treated with nitrosomethylurea.

PMID- 1979936
TI  - Di(2-ethylhexyl)phthalate alters carbohydrate enzyme activities and foci
      incidence in rat liver.
AB  - The effect of di(2-ethylhexyl)phthalate (DEHP) on diethylnitrosamine (DEN)
      initiated preneoplastic liver lesions with expression of gamma
      glutamyltranspeptidase (GGTase) and loss of adenosine triphosphatase (ATPase) as
      well as alterations of hepatic carbohydrate metabolism in male and female Sprague
      Dawley rats have been investigated. Two treatment schedules have been compared
      with respect to their sensitivity by the histochemical demonstration of
      preneoplastic islands and by the biochemical determination of alterations in
      enzyme activities of liver homogenates and of serum, the last indicating
      hepatotoxicity. For initiation, a single dose of DEN was given, followed by
      treatment with various doses of DEHP given three times weekly by gavage for 7 or
      11 consecutive weeks. As histochemical enzyme markers, the expression of positive
      GGTase as well as the deficiency in ATPase were used for identification of liver
      foci. The weanling female rats (protocol A) were found to be more sensitive to
      the carcinogenic effect of DEN in view of foci incidence than the mature male
      rats which underwent partial hepatectomy prior to DEN application. The
      administration of 200 mg DEHP/kg body wt increased the incidence of ATPase
      deficient foci in both male and female rats; however, concentrations of 1000 and
      2000 mg DEHP/kg decreased the incidence of liver foci. The number of foci with
      expression of GGTase was only slightly increased in female rats following a DEHP
      concentration of 50 mg/kg, and 200 mg/kg body wt. DEHP alone did not induce
      preneoplastic lesions that could be identified by these two markers. Biochemical
      investigations indicate that DEHP alters the metabolic pattern in liver. An
      increase of the NADP-linked enzymes glucose-6-phosphate dehydrogenase (G6PDH),
      malic enzyme, extra-mitochondrial ICDH as well as an enhancement of NAD-dependent
      alpha-G3PDH and lactate dehydrogenase were found following DEHP administration.
      On the other hand the glycolytic enzymes pyruvate kinase (PK) and enolase as well
      as the gluconeogenetic enzyme fructose-1,6-bisphosphatase (FBPase) were
      significantly reduced. In protocol B (male rats) the reactions of PK, FBPase and
      malic enzyme were more altered after DEHP exposure than in protocol A, while the
      activity of G6PDH was more increased in protocol A. Most enzymes being involved
      in the carbohydrate metabolism are influenced by DEHP in a dose-dependent manner.
      There was no increase in serum FBPase activity in both male and female rats after
      DEHP treatment but a reduction of glutamate-oxalate-transaminase and glutamate
      pyruvate-transaminase activities was observed.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1979937
TI  - Characterization of the DNA damage recognized by an antiserum elicited against
      cis-diamminedichloroplatinum (II)-modified DNA.
AB  - A series of in vitro and in vivo studies were performed to characterize DNA
      damage recognized by an antiserum elicited against DNA modified with cis
      diamminedichloroplatinum(II) (cisplatin). Adducts determined by the cisplatin-DNA
      enzyme-linked immunosorbent assay (ELISA) in human blood cell DNA have been shown
      to correlate well with positive clinical outcome in testicular and ovarian cancer
      patients receiving platinum drug-based chemotherapy (Reed et al. (1990) Proc.
      Natl. Acad. Sci., 84; 5024, and Reed et al. (1988) Carcinogenesis, 9, 1909). DNAs
      from calf thymus, salmon sperm, pBR322 and synthetic oligonucleotides were
      modified with cisplatin in vitro before or after specific DNA digestion steps to
      yield adducted samples of known size and/or chemical composition. These cisplatin
      modified DNAs were assayed by atomic absorption spectrometry (AAS) to assess
      absolute platinum content, and by ELISA to determine the antiserum specificity.
      The antiserum recognizes native cisplatin-modified calf thymus DNA, and native
      oligonucleotides containing intrastrand cis-Pt (NH3)2-d(pGpG) adducts (Pt-GG) and
      intrastrand cis-Pt (NH3)2-d(pApG) adducts (Pt-AG). Modified plasmid DNA fragments
      of varying sizes (down to 309 base pairs) are recognized similarly to cisplatin
      modified calf thymus DNA. The antiserum does not cross-react with individual Pt
      GG or Pt-AG adducts not bound to DNA. In experiments designed to assess the
      relationship between adduct measured by ELISA and total platinum bound to DNA as
      measured by AAS, male and female Sprague-Dawley rats were injected i.p. with
      cisplatin and a dose response for adduct formation was determined in kidney DNA
      samples. Values obtained by ELISA were substantially lower than those measured by
      AAS, and the two were directly related in DNA from kidney tissues of rodents but
      not in DNA from human nucleated blood cells. In rodent samples the ELISA measured
      a consistent 0.2% of the total DNA-bound platinum determined by AAS, with a
      correlation coefficient of 0.91. Among 54 blood cell DNA samples from human
      patients, which gave measurable adduct values in both ELISA and AAS, the ELISA
      measured a variable fraction (0.2-33.0%) of the total DNA-bound platinum measured
      by AAS. We conclude that the cisplatin-DNA ELISA measures a three dimensional
      lesion in DNA that is formed in direct proportion to total DNA-bound platinum in
      rat kidney, but that in human biological samples, interindividual variability
      precludes a relationship that conforms to simple mathematical algorithms.

PMID- 1979938
TI  - Differential upregulation of intercellular adhesion molecule-1 in coeliac
      disease.
AB  - The expression of intercellular adhesion molecule-1 (ICAM-1) was studied on
      peroral jejunal biopsies from patients with coeliac disease. The biopsies from
      untreated patients exhibited greater staining of the superficial lamina propria
      cells compared with treated patients and controls. A gluten challenge in treated
      patients produced an altered staining pattern within 2 h. The results demonstrate
      the role of ICAM-1 expression in coeliac disease, providing further evidence for
      the role of lamina propria cells in the pathogenesis of this condition.

PMID- 1979939
TI  - A T cell receptor beta chain polymorphism is associated with patients developing
      insulin-dependent diabetes after the age of 20 years.
AB  - We have studied the BglII polymorphism near the T cell receptor beta chain
      constant region (TcR-C beta) gene, HLA-DR genotypes and certain autoimmune
      features in 102 patients with type I (insulin-dependent) diabetes. There was a
      significant decrease in the frequency of the 1:1 genotype (P = 0.008) and an
      increase in the 1:2 genotype (P = 0.03) of the BglII TcR polymorphism in the
      group of patients who developed type-I diabetes after the age of 20 years. This
      group of patients also showed an increased incidence of autoantibodies
      (especially islet cell antibody), a family history of diabetes and the presence
      of other autoimmune diseases. The frequency of this polymorphism in patients who
      developed type I diabetes before the age of 20 years was similar to a non
      diabetic group. These results suggest that there are two genetically distinct
      groups of patients with type I diabetes. HLA-DR3 and HLA-DR4 genotypes were also
      increased in the diabetic patients but no significant difference was observed
      between HLA-DR genotypes, the TcR-C beta genotypes, the age of diagnosis or with
      other autoimmune features. Patients developing type I (insulin-dependent)
      diabetes after the age of 20 years have an additional genetic susceptibility for
      diabetes associated with the TcR-C beta gene.

PMID- 1979941
TI  - Electroretinographic effects induced in humans by psychopharmacologic agents.
AB  - We studied the effects of single doses of different dopamine agonists and
      antagonists on the electroretinogram of a group of healthy volunteers. The
      results demonstrated significant b-wave amplitude changes after drug
      administration, suggesting that electroretinograms can be employed to evaluate
      the effects on retinal dopaminergic activity induced by psychotropic drugs and
      that the study of the electroretinographic effects of psychopharmacologic agents
      can provide new insights into the relationship between retinal dopaminergic
      mechanisms and the electroretinogram b-wave origin.

PMID- 1979940
TI  - Isolation, characterization, and physical localization of 33 human X-chromosome
      RFLP markers.
AB  - In a search for highly polymorphic X-specific loci, the X-chromosome DOE Ch35
      phage library (LAOXNL01) was screened with three oligonucleotides representative
      of minisatellite consensus sequences. A total of 170 clones containing human
      inserts were isolated by hybridization to the oligonucleotide sequences; each was
      tested for polymorphism on five random female DNAs with six restriction enzymes.
      Among the 53 clones demonstrating a polymorphic pattern, 47 were of distinct
      origin. Twelve of the polymorphisms (23%) were determined to be autosomal.
      Polymorphisms for the remaining 35 clones were characterized, These polymorphisms
      represent 33 new X-chromosome RFLP loci, since two pairs of clones detected
      partially overlapping patterns. A pattern of similar length variation with
      multiple enzymes ("VNTR-type") was demonstrated in 6 (50%) of the 12 non-X
      polymorphic clones. However, only 3 (9%) of the 33 X polymorphic loci showed VNTR
      like patterns, suggesting a decreased amount of VNTR polymorphism on the X
      chromosome. The 33 polymorphic X loci were physically localized with a set of
      rodent x human somatic cell hybrid DNAs representing nine different X-chromosome
      breakpoints.

PMID- 1979942
TI  - [Results of a survey on the use of delayed-action neuroleptics in psychiatry].
AB  - Depot neuroleptics have been empirically used for 30 years by psychiatrists. An
      inquiry was performed among private and public psychiatrists. The goal of the
      study was to understand the prescription rules of depot neuroleptics. A
      questionnaire was systematically sent to all psychiatrists working in Loire
      Atlantique. The answer rate was 41.4% which is quite good for this kind of
      inquiry. The main indications of depot neuroleptics were chronic deliria and
      schizophrenia. Dosages are not accorded to negative or productive symptoms.
      Therapists do not think that there are efficacy differences between marketed
      drugs. Few of them use therapeutic windows. Prescriptions were not adjusted
      following drug pharmacokinetic parameters. So this work lays down rules about
      rational prescriptions and drug monitoring of depot neuroleptic concentrations.

PMID- 1979943
TI  - [Prescription of neuroleptics for children].
AB  - The discovery of neuroleptics has certainly not had the same impact in child
      psychiatry as it has had in adult psychiatry. Yet, these substances are widely
      used with children. Prescription is generally based on a few simple rules:
      treatment is started with low doses which are progressively increased, so as to
      reach an optimal posology which establishes a balance between clinical efficiency
      and side effects; plasmatic levels may be monitored on a regular basis. The
      emergence of adverse effects continues to remain the essential preoccupation of
      the clinical practitioner; it is the reason why so many treatment plans are
      discontinued (on a short term basis, acute dyskinesia, sedation, hypotension,
      weight gain; on a long-term basis, passiveness, tardive dyskinesia, but this is
      seldom observed in children). As a result, one must be careful in prescribing
      neuroleptics to youngsters and consider other drugs whenever possible. Following
      a brief review of the kinetic specificities of neuroleptics in children, we
      describe the general modalities of prescription for this age group and give some
      personal results as illustrative examples. We then discuss the issue of tolerance
      and side effects.

PMID- 1979944
TI  - [Use of electroconvulsive therapy in adolescence].
AB  - Few studies report the use of ECT in adolescents. Within a period of 3 years, 9
      patients aged 15 to 19 were treated by ECT in our department. Indications were
      acute schizophrenia, delusional depression and delusional mania, resistant to
      usual medication. ECT proved to be a safe treatment with good short-term outcome.
      Long-term outcome did not seem to be modified by treatment. These results are
      discussed in relation to the use of ECT in adults and adolescents reported in the
      literature.

PMID- 1979946
TI  - The effects of the partial beta 1-agonist xamoterol on heart rate and ventricular
      arrhythmias in patients with mild to moderate heart failure.
AB  - A major concern with the use of oral inotropes in chronic heart failure is their
      propensity to exacerbate cardiac arrhythmias. In a double-blind randomized
      placebo-controlled crossover study of xamoterol, a novel beta 1-partial agonist,
      24 h ambulatory electrocardiograms were obtained in 26 patients prior to and at
      the end of 13-week treatment periods. During treatment with xamoterol there was
      no significant change in mean hourly number of ventricular extrasystoles compared
      with baseline and placebo (30 +/- 17 vs 56 +/- 42 and 18 +/- 7, respectively), or
      in the number of patients showing complex forms (multiform VEs, pairs,
      ventricular tachycardia) (20/26 vs 19/26 and 19/26, respectively), or ventricular
      tachycardia alone (5/26 vs 4/26 and 6/26, respectively). Xamoterol therapy also
      stabilized heart rate variability over the 24 h period.

PMID- 1979945
TI  - An autoregulatory enhancer element of the Drosophila homeotic gene Deformed.
AB  - The stable determination of different anterior-posterior regions of the
      Drosophila embryo is controlled by the persistent expression of homeotic selector
      genes. One mechanism that has been proposed to explain the persistent expression
      of the homeotic gene Deformed is an autoactivation circuit that would be used
      once Deformed expression had been established by earlier acting patterning genes.
      Here we show that a large cis-regulatory element mapping approximately 5 kb
      upstream of the Deformed transcription start has the properties predicted for a
      Deformed autoregulatory enhancer. This element provides late, spatially localized
      expression in the epidermal cells of the maxillary and mandibular segments which
      is wholly dependent upon endogenous Deformed function. In addition, the
      autoregulatory enhancer can be activated ectopically in embryos and in imaginal
      disc cells by ectopic expression of Deformed protein. Deletion analysis of the
      autoregulatory element indicates that it contains compartment specific sub
      elements similar to those of other homeotic loci.

PMID- 1979947
TI  - Morphometry and function of islet cells after different forms of drainage at
      pancreatic transplantation in rats.
AB  - The survival of endocrine cells of the islets is crucial for a successful
      transplantation of the pancreas in the treatment of diabetes mellitus. In the
      present investigation, we compared the effect of four techniques of whole
      pancreas transplantation in rats on the endocrine cells of islets of Langerhans.
      Impairment of the endocrine function of the pancreas with a decrease in the k
      value was seen after 6 months in the group with duct ligation, and after 12
      months in the groups with latex and ethibloc occlusion. An open pancreatic duct
      maintains a more stable endocrine function than in duct-ligated or occluded
      grafts. Fasting plasma insulin and somatostatin were elevated in transplanted
      rats. Whichever method of transplantation we chose, the cell ratio remained
      unchanged compared with the control group, even after 12 months. Therefore, only
      intact islet architecture enables a normal endocrine pancreatic function.

PMID- 1979948
TI  - Diet- and hormone-induced reversal of the carbamoylphosphate synthetase mRNA
      gradient in the rat liver lobulus.
AB  - A hybridocytochemical analysis of adult liver from normal control and from
      hormonally and dietary-treated rats was carried out, using radioactively-labelled
      probes for the mRNAs of glutamine synthetase (GS), carbamoylphosphate synthetase
      (CPS) and phosphoenolpyruvate carboxykinase (PEPCK). In line with previous
      findings, GS mRNA is exclusively expressed in a small pericentral compartment,
      CPS mRNA exclusively in a contiguous large periportal compartment and PEPCK mRNA
      across the entire porto-central distance. The density of labelling in CPS and
      PEPCK mRNA-positive hepatocytes decreases in a porto-central direction.
      Starvation resulted in a reversal of the gradient of CPS mRNA within its
      periportal compartment; glucose refeeding counteracted this effect. Livers of
      glucocorticosteroid-treated, starved or diabetic rats also revealed a reversal of
      the normal gradient of CPS mRNA, but now across the entire porto-central
      distance. The patterns of expression of GS and PEPCK mRNA remained essentially
      unchanged, notwithstanding substantial changes in the levels of expression. It is
      concluded that blood-borne factors constitute the major determinants for the
      expression patterns of CPS mRNA within the context of the architecture of the
      liver lobulus.

PMID- 1979949
TI  - Molecular conformation of achatin-I, an endogenous neuropeptide containing D
      amino acid residue. X-ray crystal structure of its neutral form.
AB  - The molecular conformation of achatin-I neutral form (H-Gly-D-Phe-Ala-Asp-OH), an
      endogenous neuropeptide, was elucidated by X-ray crystal analysis. The molecule
      has a type II' beta-turn structure with the D-Phe-Ala residues at the corner of
      the bend, which is further stabilized by two NH(Gly)...C gamma = O sigma(Asp) and
      NH(Asp)...C gamma = O sigma(Asp) intramolecular hydrogen bonds. This turn
      conformation may be an important feature of achatin-I related to its
      neuroexcitatory activity.

PMID- 1979950
TI  - Characteristics of insulin resistance in Turner syndrome.
AB  - The characteristics of insulin resistance, in Turner syndrome are still unclear.
      For this purpose in 4 patients with Turner syndrome and in 8 control females we
      performed an euglycaemic hyperinsulinemic glucose clamp at the following insulin
      infusion rates (50 and 100 mU/Kg x h), each period lasting 120 min. A
      simultaneous infusion of D-3-H-glucose allowed us to determine in basal
      conditions and during the clamp hepatic glucose output and glucose disappearance
      rate (Rd). In basal conditions plasma glucose (4.8 +/- 0.1 vs 4.6 +/- 0.2 mmol/1
      p = NS) and plasma glucagon (102 +/- 7.5 vs 112 +/- 11.3 ng/l p = NS) were
      similar in both groups despite higher plasma insulin (19 +/- 1.8 vs 7 +/- 2.2
      mU/l p less than 0.05) and C-peptide (1.0 less than 0.1 vs 0.8 +/- 0.06 pmol/l p
      less than 0.05) levels in patients with Turner syndrome. In the last 60 min of
      the lower insulin infusion rate glucose infusion rate (4.1 +/- 0.3 vs 2.9 +/- 0.4
      mg/Kg x min p less than 0.05) and glucose disappearance rate (3.89 +/- 0.12 vs
      2.63 +/- 0.11 mg/Kg x min p less than 0.01) were significantly reduced in
      patients with Turner. On the contrary hepatic glucose output was similarly
      suppressed in both groups of subjects. Doubling the insulin infusion rate, we
      obtained similar results in patients and controls respectively. So we conclude
      that in Turner syndrome the insulin resistance state is mainly due to a muscular
      receptor defect.

PMID- 1979952
TI  - Technology assessment should be a joint effort.

PMID- 1979951
TI  - Age-dependent hepatic lipogenic enzyme activities in starved-refed rats.
AB  - Food intake, plasma glucose, insulin (I) and triiodothyronine (T3) and liver
      glucose 6-phosphate dehydrogenase (G6P-DH), malic enzyme (ME). ATP-citrate lyase,
      acetyl-CoA carboxylase (AcCoACx) and fatty acid synthase (FAS) activities were
      measured in 2 and 22 months old rats before, after 3 d starvation and 2,4,6. 24
      and 48 h refeeding a high carbohydrate (74% w/w) diet. Expressed per 100 g of
      body weight, the carbohydrate intake of old rats was 55% lower than that of young
      rats. Plasma insulin was higher in old than in young rats and decreased (-40%)
      after starvation and returned to control values 4 h after refeeding. In young
      rats plasma insulin fell after starvation (-85%) and returned to normal values 2
      h after refeeding. No significant differences were observed in plasma [T3]
      between the two groups. During the first 6 h of refeeding, plasma glucose
      increased 2-fold and returned to control values after 24 h in young rats. In old
      rats, plasma glucose returned to its control value after 2 h. Compared to the
      starved level, 48 h after refeeding, G6P-DH, ME, ATP-citrate lyase, AcCoACx and
      FAS activities increased 5- to 6-fold in young rats, while in old rats the
      increase was much smaller and represented 35% of that observed in young rats.
      These results suggest, that the age-related reduction in inducibility of hepatic
      lipogenic enzymes of rats refed a high carbohydrate diet after starvation may be
      due to a spontaneous decrease in the carbohydrate intake and to a decrease
      effectiveness of insulin (insulin resistance).

PMID- 1979953
TI  - Taxol treatment of experimental proliferative vitreoretinopathy.
AB  - Taxol is a potent stabilizer of microtubules, and inhibitor of in vitro
      replication, migration, and contraction of fibroblasts. It has been found to
      limit the development of experimental tractional retinal detachments in
      nonvitrectomized rabbit eyes. We used taxol in vitrectomized, phakic rabbit eyes
      with experimentally induced proliferative vitreoretinopathy and tractional
      retinal detachments. Taxol was dissolved in 30% DMSO because of poor aqueous
      solubility. A single 0.1 ml intravitreal dose of 2 x 10(-4) M taxol in 30% DMSO
      was injected immediately after 250,000 heterologous corneal fibroblasts had been
      injected; 0.1 ml of 30% DMSO was injected into control eyes. Taxol reduced the
      incidence of tractional retinal detachments seen 3-4 weeks later. When taxol
      injection was delayed for 3 days after the initial intravitreal injection of
      fibroblasts into nonvitrectomized eyes, the extent of retinal detachments was
      reduced, but the incidence of retinal detachment was unchanged from the untreated
      eyes at the end of 4 weeks. These data indicate that taxol may be most useful
      when given early in the course of proliferative vitreoretinopathy.

PMID- 1979955
TI  - The inhibition of thromboxane A2 release by beta-sympathomimetics.

PMID- 1979954
TI  - Experimental non-steroidal anti-inflammatory drug-induced enteropathy in the rat:
      similarities to inflammatory bowel disease and effect of thromboxane synthetase
      inhibitors.
AB  - We have validated an established animal model of acute inflammatory bowel disease
      in indomethacin-treated rats. Studies in both in vitro and in vivo 51chromium
      labelled ethylenediamine tetra-acetate (51Cr-EDTA) permeability and tissue
      myeloperoxidase activity, a marker of inflammatory cell invasion, showed
      increased permeability and enzyme levels, respectively, in treated animals
      compared to controls (in vitro 51Cr-EDTA permeability: (mean (SE] control 0.10
      (0.02) microliter/mg per tissue, experimental 0.17 (0.02) (p < 0.01, 2 way
      analysis of variance); in vivo 51Cr-EDTA permeability: control 3.9 (1.3) (% dose
      recovered), experimental 12.1 (1.5) (p < 0.01); tissue myeloperoxidase: control
      10.8 (0.4) mU/mg, experimental 17.2 (0.5) p less than 0.01). Pretreatment or
      simultaneous treatment of indomethacin-treated animals with glucocorticoids,
      sulphasalazine, or tetracycline reduced the permeability changes and the tissue
      inflammatory response (in vitro 51Cr-EDTA permeability: (mean (SE] sulphasalazine
      + indomethacin 0.11 (0.2) microliter/mg tissue (p < 0.01), prednisolone +/-
      indomethacin 0.12 (0.02) (p < 0.01), tetracycline + indomethacin 0.12 (0.02) (p <
      0.01]. Glucocorticoids and sulphasalazine, but not tetracycline, administered
      after the indomethacin also partially corrected the permeability and inflammatory
      changes induced by indomethacin (in vitro 51Cr-EDTA permeability: sulphasalazine
      0.15 (0.02) microliter/mg, p < 0.02; prednisolone 0.12 (0.02) microliter/mg, p <
      0.01). This approach was used to investigate the effects of two different
      thromboxane synthetase inhibitors in indomethacin-treated animals. Simultaneous
      treatment with thromboxane synthetase inhibitors and indomethacin prevented the
      51Cr-EDTA permeability and tissue myeloperoxidase increases induced by
      indomethacin alone (in vitro 51Cr-EDTA permeability: thromboxane synthetase
      inhibitors + indomethacin 0.11 (0.01) microliter/mg (p0.01); tissue
      myeloperoxidase: 11 (0.4) mU/mg, (p < 0.01). Thromboxane synthetase inhibitors
      administered after the indomethacin also partially corrected the permeability and
      inflammatory changes induced by indomethacin (in vitro 51Cr-EDTA permeability:
      thromboxane synthetase inhibitors 0.12 (0.02) mU/mg (p < 0.01); tissue
      myeloperoxidase 13.8 (0.5) (p < 0.01). These studies indicate that thromboxane
      synthetase inhibitors partially correct the intestinal lesion non-steroidal anti
      inflammatory drug enteropathy and may therefore be of use in inflammatory bowel
      diseases in humans.

PMID- 1979956
TI  - Defective, deleted or converted CYP21B gene and negative association with a rare
      restriction fragment length polymorphism allele of the factor B gene in
      congenital adrenal hyperplasia.
AB  - Defects in the enzyme, steroid 21-hydroxylase, result in congenital adrenal
      hyperplasia (CAH), a common autosomal recessive disorder of cortisol
      biosynthesis. The gene encoding this protein (CYP21B) and a closely linked
      pseudogene (CYP21A) have been mapped in the HLA complex on chromosome 6p,
      adjacent to the complement genes C4B and C4A, about 80 kb from the factor B gene.
      Molecular analyses of patients with CAH have shown that the cause of the defect
      may be either a deletion, a point mutation or a conversion of the active gene.
      Linkage of the disease to HLA has previously been studied by several groups. We
      have analyzed DNAs from patients with classical and non-classical CAH and from
      their family members, by probing with CYP21, C4 and BF cDNAs. In 70% of the CAH
      haplotypes studied, the defective CYP21B gene was indistinguishable from its
      structurally intact corresponding gene in Southern blot analysis, and presumably
      bore point mutations. In the remaining chromosomes, evidence for gene
      conversions, deletions and various deleterious mutations of the CYP21B gene is
      given. Moreover, our linkage studies show that a polymorphic TaqI cleavage site
      in the factor B gene, recently described by us, may be a new and useful genetic
      marker, because we found this TaqI restriction site only in unaffected haplotypes
      carrying functional CYP21B genes and, therefore, in negative association with the
      defective CYP21B gene.

PMID- 1979957
TI  - Analysis of gene-dosage effects on the expression of CD18 by trisomy 21
      lymphoblastoid cell-lines using a statistical model to fit flow cytometry
      profiles.
AB  - It is not clear whether Down syndrome, the phenotypic expression of
      constitutional trisomy for chromosome 21 (T21), is the result of generalised
      disruption of homeostasis resulting from genetic imbalance, or the over
      expression of specific genes on chromosome 21. In order to understand the effect
      of gene dosage more clearly, we have analysed the predicted and actual levels of
      expression of the leucocyte integrin beta subunit CD 18 on the surface of T21
      leucocytes. Previous studies showed that CD18 expression by T21 lymphoid cell
      lines (LCL) is greater than on normal LCL. We have now developed a computer model
      that compares the observed and predicted CD18 flow cytometric profiles for
      trisomy 21 LCL. Three parameters (alpha, beta and gamma) have been defined that
      measure different aspects of gene dosage. Using the computer model to calculate
      these parameters, we have carried out a series of paired comparisons between
      normal and T21 LCL. The results show that, in some T21 LCL, increased CD18
      expression is proportional to the existing gene dosage, in another set the effect
      is additive, whereas in others there is a combination of proportional and
      additive effects. The results suggest that gene regulation can exert pleiotropic
      effects on gene-dosage, and is consistent with a model in which gene dosage
      itself is the cause of disrupted homeostasis.

PMID- 1979959
TI  - Germinal mosaicism from grand-paternal origin in a family with Duchenne muscular
      dystrophy.
AB  - We have identified a Duchenne muscular dystrophy (DMD) pedigree with an
      unexpected pattern of inheritance. Using marker restriction fragment length
      polymorphisms detected by probes that lie within and outside the DMD gene, we
      could demonstrate that the maternal grandfather has transmitted two distinct
      types of X chromosomes to his offspring. This original observation may be
      explained by postulating that the DMD mutation must have occurred during mitosis
      in early germline proliferation, leading to a germline mosaicism within this male
      ancestor.

PMID- 1979958
TI  - Association analysis of lipid levels and apolipoprotein restriction fragment
      length polymorphisms.
AB  - We have analyzed the correlation between restriction site variants (RFLPs;
      restriction fragment length polymorphisms) of the apolipoprotein AI, AII, B, CI
      and CII genes and serum lipid levels in a sample of male Norwegians. We find no
      significant association between any of the RFLPs and lipid levels.

PMID- 1979960
TI  - BglII restriction fragment length polymorphisms at the human p53 gene locus.

PMID- 1979961
TI  - Beta-globin gene haplotypes in Polynesians are predominantly southern Chinese in
      type.
AB  - beta-Globin gene haplotypes obtained in Polynesian Samoans were similar to those
      described in Southern Chinese. An atypical HindIII restriction fragment length
      polymorphism detected with pRK29, a 3' beta-globin gene probe, was present at a
      gene frequency of 7% in Samoans. Haplotype patterns suggest that this
      polymorphism may have arisen by 1 or 2 mutational events. DNA haplotypes derived
      from the beta-globin gene cluster confirm nuclear and mitochondrial DNA data that
      Polynesian precursor populations were East Asian in origin.

PMID- 1979962
TI  - Restriction fragment length polymorphism of the D5S4 locus in Italy.
AB  - Five Italian samples were examined for an EcoRI restriction fragment length
      polymorphism associated with a DNA sequence of unknown function, located on
      chromosome 5. No significant difference was observed between the samples. The
      allele frequencies in Italy were D5S4ES = 0.697, D5S4EF = 0.303.

PMID- 1979963
TI  - [Press workshop "HIV infection risk in the hospital for patients and medical
      personnel"; Cologne, July 24, 1990].

PMID- 1979964
TI  - Trophic effects of enkephalin, beta-endorphine and dynorphine on ventral spinal
      cord in culture.
AB  - We studied trophic effects of enkephalin (ENK), beta-endorphine (END) and
      dynorphine (DYN) on explanted cultures of ventral spinal cord from 13-14 day old
      rat embryo. The addition of each of these three neuropeptides to the growth
      medium caused no changes in neurite extension and in increased number of glial
      cells compared to control samples. The results indicate that neurite appearance
      is neither prompted nor inhibited by addition of ENK, END and DYN. It is
      considered that ENK, END and DYN are not growth factor of cultured ventral spinal
      cord of rat embryo.

PMID- 1979965
TI  - Melanocyte-stimulating hormone and persistent tardive dyskinesia: a hypothesis.
AB  - An increased incidence of abnormal perioral movements has recently been reported
      in drug-naive pinealectomized rats with further accentuation of these movements
      following administration of haloperidol. Analysis of the temporal course of the
      development of the perioral dyskinetic movements revealed that the onset of these
      movements occurred within 4 days postoperatively and peaked at 3 weeks to plateau
      over the following 4-6 weeks. Increased pituitary Melanocyte-stimulating hormone
      (MSH) content has been reported in pinealectomized rats. Elevation of MSH content
      in the pinealectomized rats occurred within 3 days of surgery and was followed by
      normalization within 4 weeks. These findings suggest that compensatory mechanisms
      involving hypothalamic-pituitary MSH release must have been activated to induce
      normalization of pituitary MSH levels. Moreover, reduction of pituitary MSH
      levels may have coincided with attenuation in the severity of the perioral
      dyskinetic movements. It is possible that the development of tardive dyskinesia
      (TD) may in part be associated with increased brain and plasma MSH levels and
      that impaired hypothalamic-pituitary regulatory mechanisms of MSH release may be
      associated with persistent TD. The pineal gland may be implicated in this process
      as diminished melatonin secretion may be associated with disinhibition of MSH
      release. Thus, the above hypothesis complements and extends the recently
      presented "melatonin hypothesis" and suggests that research of pineal
      hypothalamic interactions may be crucial to the further understanding of TD.

PMID- 1979966
TI  - Paroxysmal episodes of rapid blinking during hallucinatory activity in a
      schizophrenic patient: a possible mechanism involving pineal-mediated 'fine
      tuning' of dopaminergic functions.

PMID- 1979967
TI  - The relationship of pineal calcification to tardive dyskinesia.

PMID- 1979969
TI  - Tardive dyskinesia associated with depression in a bipolar patient: possible role
      of melatonin.
AB  - Several clinical studies have suggested that patients with affective disorder are
      at high risk for developing tardive dyskinesia (TD). An intriguing aspect of the
      relationship between TD and affective disorders involves mood dependent
      alterations in the severity of TD in bipolar patients. In most reported cases,
      depressive episodes have been reported to be associated with exacerbation of TD,
      while manic episodes were accompanied by attenuation of TD. Current neurochemical
      hypotheses of TD do not explain adequately the relationship of TD to depression
      or mania in bipolar patients. A patient with bipolar illness is presented in whom
      TD emerged concurrently with the onset of depression that developed during
      management of an acute manic episode. It is suggested that decline in melatonin
      secretion with onset of the depression was associated with the emergence of TD.
      Thus, the increased incidence and risk of TD in bipolar patients may in part be
      related to decreased melatonin secretion, while increased melatonin secretion
      during manic episodes may have protective effect against the development of TD.

PMID- 1979968
TI  - MIF-induced augmentation of melatonin functions: possible relevance to mechanisms
      of action of MIF-1 in movement disorders.
AB  - MIF-1, a synthetic tripeptide with MSH-release inhibitory properties, has been
      reported to improve symptoms of Parkinson's disease, attenuate levodopa-related
      dyskinesias and diminish the dyskinetic movements of Tardive dyskinesia. More
      recently, MIF-1 has been reported partially to protect against the nigro-striatal
      dopamine depleting effects of MPTP in mice, raising the possibility that it may
      exert protective effects against the development of Parkinson's disease. There is
      evidence to suggest that MIF-1 increases nigro-striatal dopaminergic activity,
      but its ability to improve symptoms in patients with Parkinson's disease,
      levodopa-related dyskinesias and Tardive dyskinesia cannot be explained solely on
      the basis of the drug's effect on striatal dopaminergic neurons. MIF-1 has been
      reported to potentiate the melanocyte-lightening effect of melatonin in rats and
      its effects in patients with Parkinson's disease and Tardive dyskinesia are
      associated with marked mood elevation. It is, therefore, possible that the
      effects of MIF-1 in movement disorders are associated with increased melatonin
      secretion. Thus, hypothalamic MIF may modulate nigro-striatal dopaminergic
      functions in part via pineal melatonin. Such an interaction represents a novel
      mechanism by which hypothalamic peptides act to modulate the expression of
      movement disorders.

PMID- 1979970
TI  - The association of pineal calcification with drug-induced dystonic movements.
AB  - There is evidence that reduced melatonin secretion is associated with the
      pathophysiology of neuroleptic-induced movement disorders including tardive
      dyskinesia and Parkinsonism. It has been recently reported that pinealectomized
      rats developed increased incidence and severity of spontaneous chewing movements
      compared to normal controls. Increased chewing movements in rats has been
      suggested to reflect acute drug-induced dystonias in humans. To investigate the
      relationship between melatonin secretion and the pathophysiology of neuroleptic
      induced dystonic movements, the presence and size of pineal calcification (PC) on
      CT scan was studied in relation to the severity of dystonic movements in 34
      neuroleptic-treated chronic schizophrenic patients. The incidence of
      pathologically enlarged PC (greater than 1 cm in diameter) in the schizophrenic
      patients was 8-9 times greater than the incidence reported in the literature
      among nonpsychiatric patients. In addition, there were significant differences (p
      less than .0001) between the severity of dystonic movements in patients with no
      PC and those with pathologically enlarged PC, and between the severity of the
      dystonic movements in patients with PC of less than 1 cm and those with PC of
      greater than 1 cm diameter. These findings indicate an association between the
      pathophysiology of neuroleptic-induced dystonic movements and the presence of
      enlarged PCs and suggest that disturbances of melatonin secretion is associated
      with the emergence of neuroleptic-induced dystonic movements in schizophrenic
      patients. Further studies using direct measurements of plasma melatonin levels
      are required more precisely to confirm the association between pineal melatonin
      secretion and the pathophysiology of drug-induced dystonic movement disorders.

PMID- 1979972
TI  - The characterization of beta adrenoceptor subtypes in the rat amygdala and
      hippocampus.
AB  - (-)-[125I]Iodocyanopindolol [-]ICYP), is a ligand with high specific activity and
      nearly equal affinity for beta 1 and beta 2 adrenoceptors in a variety of
      tissues. Unfortunately, (-)ICYP also has affinity for 5HT1B serotonin receptors.
      To get an accurate estimate of beta adrenoceptors in the rat amygdala and
      hippocampus, (-)ICYP binding studies were done with membranes from these limbic
      structures in the presence of 10 microM serotonin to prevent the binding of (
      )ICYP to serotonin receptors. Under these conditions. (-)ICYP binding to
      amygdaloid and hippocampus membrane preparations is saturable and reversible.
      Scatchard analyses revealed in both regions a single class of binding sites with
      an equilibrium dissociation constant (KD) of 18.5 pM for the amygdala and 19.6 pM
      for the hippocampus. The hippocampus has a significantly lower density of binding
      sites (Bmax) than amygdala (51.6 vs 62.3 fmol/mg membrane protein, p less than
      .05). The two brain regions do not differ with respect to kinetic reactions in
      that both show comparable slow association and dissociation rates. However, the
      dissociation reactions do reveal two affinity states for the binding sites in
      both areas. Detailed competition analyses with beta adrenoceptor subtype
      selective drugs (ICI-89406 and ICI-118551) show that in both regions about 70% of
      the beta adrenoceptor population is of the beta 1 subtype with the remainder
      being beta 2 subtype.

PMID- 1979971
TI  - Pineal calcification and subtypes of tardive dyskinesia.
AB  - There is evidence that reduced melatonin secretion is associated with the
      pathophysiology of tardive dyskinesia (TD). To investigate the relationship
      between melatonin secretion and TD, I evaluated scores of subtypes of TD with CT
      scan measurements of pineal calcification (PC) size in 77 chronic
      institutionalized schizophrenic and bipolar patients. There was a significantly
      greater incidence of pathologically enlarged calcified pineal glands (greater
      than 1 cm in diameter) in the patients (18.1%) compared to the reported incidence
      in the literature in nonpsychiatric subjects (1%). In addition, there was a
      significant association between scores of limb-axial (but not orofacial)
      dyskinesias and the presence of pathologically enlarged PC (p less than 0.05).
      These findings support the notion that the pathophysiology of orofacial
      dyskinesias may be distinct from limb-axial dyskinesias. In addition, since it is
      possible that a pathologically enlarged calcified pineal gland is associated with
      reduced melatonin secretion, these findings add further support to implicate
      decreased melatonin secretion in the pathophysiology of TD. Further studies using
      direct measurements of plasma melatonin levels are required to define more
      precisely the relationship between TD and melatonin secretion.

PMID- 1979973
TI  - Topographic subtypes of tardive dyskinesia: relationship to seborrhea.

PMID- 1979974
TI  - Suppression by adrenoceptor beta-agonists of vascular permeability increase and
      edema formation induced by arachidonate metabolites, platelet-activating factor,
      and tumor-promoting phorbol ester TPA.
AB  - Air-pouch-type inflammation was induced by injecting sodium carboxymethyl
      cellulose solution containing leukotriene C4 (LTC4, 3.20 x 10(-7) M, 0.2
      micrograms/ml) and prostaglandin E2 (PGE2, 5.68 x 10(-6) M, 2.0 micrograms/ml),
      platelet-activating factor (PAF, 1 x 10(-6) M, 0.52 micrograms/ml), or 12-O
      tetradecanoyl phorbol 13-acetate (TPA, 1.62 x 10(-6) M, 1.0 micrograms/ml) into
      an air pouch made on the dorsum of rats. Vascular permeability and tissue edema
      formation were significantly increased by injecting the phlogogen solution. The
      histamine level in the pouch fluid was dramatically increased by injecting TPA
      but not by LTC4 and PGE2, or PAF. Injection of isoproterenol or procaterol with
      the phlogogen solution produced dose-dependent suppression of both vascular
      permeability increase and tissue edema formation. However, the TPA-induced
      increase in the histamine level was not suppressed in parallel with the decrease
      of vascular permeability or tissue edema formation. These results indicate that
      beta-agonists suppress vascular permeability response and local tissue edema
      formation not by inhibiting mast cell degranulation, but by inhibiting the
      reactivity of the local vasculature to chemical mediators such as arachidonate
      metabolites, PAF, and histamine and serotonin released from mast cells.

PMID- 1979975
TI  - Production of both 8-hydroxydeoxyguanosine in liver DNA and gamma
      glutamyltransferase-positive hepatocellular lesions in rats given a choline
      deficient, L-amino acid-defined diet.
AB  - The comparative carcinogenic activities of a choline-deficient, L-amino acid
      defined diet (CDAADD) and a purified choline-deficient diet (CDD) for rat liver
      were studied in terms of both 8-hydroxydeoxyguanosine induction, a marker of DNA
      damage induced by oxidative stress, and development of gamma-glutamyltransferase
      (GGT)-positive putative preneoplastic lesions, including foci and hyperplastic
      nodules. Twelve weeks after the beginning of treatment, DNA damage could be
      detected in the liver DNA of rats receiving either CDAADD or CDD, the degree
      being significantly greater in the former case. Similarly, while GGT-positive
      liver lesions were induced by both CDAADD and CDD, the numbers were higher and
      the areas of lesions were larger in rats receiving CDAADD than in those given
      CDD. Histologically, hyperplastic nodules were induced in the livers of animals
      administered CDAADD whereas only foci were seen in the CDD case. The results thus
      indicate that oxidative stress might be directly involved in rat liver
      carcinogenesis by CDD and, to a greater degree, with CDAADD.

PMID- 1979976
TI  - Heterogeneity of proliferative activity in nodule-in-nodule lesions of small
      hepatocellular carcinoma.
AB  - Surgically resected small hepatocellular carcinomas showing "nodule-in-nodule"
      formation were analyzed in terms of cell proliferative activity. The analysis was
      achieved by successful immunohistochemical demonstration of proliferating cell
      nuclear antigen in formalin-fixed paraffin-embedded tissue sections. Eight
      nodules (up to 3 cm in diameter) examined were either atypical adenomatous
      hyperplasia or hepatocellular carcinoma of low histologic grade, containing a
      discrete inner nodular area composed of obvious hepatocellular carcinoma of
      higher histologic grade. In all cases, the proliferating cell nuclear antigen
      labeling index of the latter area was much higher than that of the former, which
      in turn was slightly higher than that of the non-cancerous liver of the patient
      in 6 cases. The data presented here provide supporting evidence that the
      successive emergence and expansion of a more rapidly proliferating subclone
      within a nodule result in the stepwise progression of malignancy of human
      hepatocellular carcinoma.

PMID- 1979978
TI  - Blood sucking insects and transmission of HIV infection.

PMID- 1979977
TI  - Monoclonal anti-P-glycoprotein antibody-dependent killing of multidrug-resistant
      tumor cells by human mononuclear cells.
AB  - Mouse monoclonal antibodies (MRK16 and MRK17) against human multidrug-resistant
      cancer cell lines were tested for antibody-dependent cytotoxicity mediated by
      human blood mononuclear cells, using a 4-h 51Cr release assay. MRK16 (IgG2a
      isotype) was shown to be more effective than MRK17 (IgG1 isotype). Moreover, when
      four pairs of drug-resistant and their parent sensitive human cancer cells were
      tested for antibody-dependent cell-mediated cytolysis (ADCC) using MRK16, only
      the drug-resistant cell lines were susceptible to ADCC reaction. When highly
      purified lymphocytes (greater than 99%) and monocytes (greater than 97%) were
      isolated from blood mononuclear cells by centrifugal elutriation and adherence,
      MRK16 promoted both lymphocyte- and monocyte-mediated tumor cell killing, whereas
      MRK17 induced only a lymphocyte-mediated ADCC reaction. These results suggest
      that MRK16 of IgG2a subtype may be a useful therapeutic agent in eradication of
      drug-resistant cancer cells expressing P-glycoprotein through ADCC reaction.

PMID- 1979979
TI  - Regulation of insulin gene expression by glucose and calcium in transfected
      primary islet cultures.
AB  - To study the regulation of insulin gene expression by physiological regulators,
      primary cultures of rat islet cells were transfected with portions of the rat
      insulin I gene 5'-flanking sequence linked to the reporter gene chloramphenicol
      acetyltransferase (CAT). Incubation of the cells in increasing glucose
      concentrations led to a parallel increase in both CAT activity and CAT mRNA
      levels. Pretreatment of the cells with the beta-cell-specific toxin
      streptozotocin reduced CAT activity 97%. Beta-Cell-specific expression of CAT was
      also demonstrated by co-staining the transfected cells with antisera to both CAT
      and insulin. Experiments showing a reduction in the response to glucose in the
      presence of the calcium channel blocker verapamil suggest that calcium plays a
      role in the glucose response, possibly via regulation of factors interacting with
      this limited portion of the insulin gene.

PMID- 1979980
TI  - Site-specific phosphorylation of tyrosine hydroxylase after KCl depolarization
      and nerve growth factor treatment of PC12 cells.
AB  - The phosphorylation and activation of tyrosine hydroxylase was examined in PC12
      cells following depolarization with KCl or treatment with nerve growth factor.
      Both treatments activate tyrosine hydroxylase (TH) and increase enzyme
      phosphorylation. Site-specific analysis of the tryptic phosphopeptides of TH
      isolated from [32P]phosphate-labeled PC12 cells demonstrated that the major
      phosphorylated peptide (termed "H25") did not contain any of the previously
      reported phosphorylation sites. Phosphoamino acid analysis of this peptide
      demonstrated that the phosphorylated residue was a serine. Synthetic tryptic
      peptides containing putative phosphorylation sites were prepared, and subjected
      to high performance liquid chromatography analysis and isoelectric focusing. The
      tryptic phosphopeptide containing serine 31 comigrated with the H25 peptide
      during both of these analytical techniques. The tryptic phosphopeptide produced
      by the phosphorylation of tyrosine hydroxylase by the recently discovered proline
      directed protein kinase and the phosphorylated synthetic phosphopeptide TH2-12
      are clearly separated from H25 by this analysis. We conclude that serine 31 is
      phosphorylated during KCl depolarization and nerve growth factor treatment of
      PC12 cells and that this phosphorylation is responsible for the activation of
      tyrosine hydroxylase. Since this site is not located in a sequence selective for
      any of the "classical" protein kinases, we suggest that a novel protein kinase
      may be responsible for the phosphorylation of this site. Since serine 31 has a
      proline residue on the carboxyl-terminal side, the possibility that this kinase
      may be related to the recently reported proline-directed protein kinase is
      discussed. Other sites that are also phosphorylated on TH during KCl
      depolarization include serine 19, which is known to be phosphorylated by
      calmodulin-dependent protein kinase II. A schematic model for the regulation of
      tyrosine hydroxylase activity by phosphorylation of the NH2-terminal regulatory
      domain is presented.

PMID- 1979981
TI  - Direct photoaffinity labeling of gizzard myosin with [3H]uridine diphosphate
      places Glu185 of the heavy chain at the active site.
AB  - The active site of chicken gizzard myosin was labeled by direct photoaffinity
      labeling with [3H]UDP. [3H] UDP was stably trapped at the active site by addition
      of vanadate (Vi) and Co2+. The extraordinary stability of the
      myosin.Co2+.[3H]UDP.Vi complex (t1/2 greater than 5 days at 0 degrees C) allowed
      it to be purified free of extraneous [3H]UDP before irradiation began. Upon UV
      irradiation, greater than 60% of the trapped [3H]UDP was photoincorporated into
      the active site. Only the 200-kDa heavy chain was labeled, confirming earlier
      results (Maruta, H., and Korn, E. (1981) J. Biol. Chem. 256, 499-502) using
      [3H]UTP. Extensive tryptic digestion of photolabeled myosin subfragment 1
      followed by high performance liquid chromatography separations and removal of
      nucleotide phosphates by treatment with alkaline phosphatase allowed two labeled
      peptides to be isolated. Sequencing of the labeled peptides and radioactive
      counting showed that Glu185 was the residue labeled. Since UDP is a "zero-length"
      cross-linker, Glu185 is located at the purine-binding pocket of the active site
      of smooth myosin and adjacent to the glycine-rich loop which binds the
      polyphosphate portion of ATP. This Glu residue is conserved in smooth and
      nonmuscle myosins and is the same residue identified previously by [3H]UTP
      photolabeling in Acanthamoeba myosin II (Atkinson, M. A., Robinson, E. A.,
      Appella, E., and Korn, E. D. (1986) J. Biol. Chem. 261, 1844-1848).

PMID- 1979983
TI  - Immunohistochemical analysis of the visual wulst of the pigeon (Columba livia).
AB  - The avian wulst, a laminated "bulge" in the dorsal telencephalon, contains
      several distinct regions. The posterolateral portion (visual wulst) has been
      proposed to be an avian equivalent of the mammalian striate cortex. The present
      study examines specific neurotransmitters and neuropeptides within the visual
      wulst by immunohistochemical techniques. Antisera and monoclonal antibodies
      against choline acetyltransferase (ChAT), nicotinic acetylcholine receptor
      (nAChR), tyrosine hydroxylase (TH), serotonin (5-HT), glutamic acid decarboxylase
      (GAD), gamma-aminobutyric acid A receptor (GABAAR), cholecystokinin (CCK),
      substance P (SP), leucine-enkephalin (L-ENK), neurotensin (NT), neuropeptide Y
      (NPY), somatostatin (SRIF), corticotropin-releasing factor (CRF), and vasoactive
      intestinal polypeptide (VIP) were used. Somata and neuropil displaying specific
      immunoreactivity were generally distributed in accordance with the laminar
      cytoarchitectonic organization of the wulst. The superficial layer of the wulst,
      the hyperstriatum accessorium, contained the highest densities of TH-, 5-HT-, SP
      , NPY-, SRIF-, CRF-, and VIP-positive neuropil in the wulst, whereas the highest
      density of CCK- and NT-staining was found in the deepest layer of the wulst, the
      hyperstriatum dorsale. In addition to the traditionally defined four laminae of
      the wulst, the immunoreactive staining revealed several subregions within each
      lamina. The most dorsolateral portion of the wulst contained the highest
      densities of ChAT- and L-ENK-stained fibers in the wulst, as well as moderately
      dense staining of neuropil for 5-HT-, TH-, SP-, and CCK-like immunoreactivity.
      The nAChR-immunoreactivity was faint and distributed rather uniformly throughout
      the wulst. The results suggest that the wulst consists of multiple regional
      variations within layers comparable to laminar variations found within different
      cytoarchitectonic areas of the mammalian neocortex.

PMID- 1979982
TI  - Equivalent helper functions of human "naive" and "memory" CD4+ T cells for the
      generation of alloreactive cytotoxic T lymphocytes.
AB  - Cells comprising the CD4+ T-cell population are heterogeneous with regard to
      function, maturation, and the expression of membrane molecules such as the CD45RA
      antigen. Previous analyses of the CD4+ subsets defined by CD45RA antigen
      expression have shown that the ability to provide help for antibody production is
      restricted to cells within the CD4+CD45RA- subset. In the present studies, we
      have examined the ability of "naive" CD4+CD45RA+ cells and "memory" CD4+CD45RA-
      cells to provide help for the generation of alloreactive CD8+ cytotoxic T
      lymphocytes. When purified CD4+CD45RA+ or CD4+CD45RA- cells were cultured with
      autologous CD8+ cells and allogeneic E- stimulator cells, both subsets were
      consistently able to provide help for CD8+ cytotoxic T-cell development. In
      contrast, the ability to provide help for antibody production was restricted to
      cells in the CD4+CD45RA- subset. Differences in the mechanisms of the helper
      functions for these two systems were also identified. Whereas exogenous
      interleukin-2 (IL-2) could replace the help provided by either CD4+ subset for
      cytotoxic T-cell generation, IL-2 had only minimal effects on immunoglobulin
      production. Thus, our studies highlight the contrasting cellular requirements and
      mechanisms involved in "help" for B-cell differentiation versus cytotoxic T
      lymphocyte generation, and they show that the helper/inducer functions of human
      CD4+ cells are not mediated solely by the CD4+CD45RA- subset.

PMID- 1979984
TI  - Omeprazole in H2 receptor antagonist-resistant reflux esophagitis.
AB  - We conducted a retrospective review of 25 patients with severe reflux esophagitis
      treated with omeprazole because of failure of H2 receptor antagonists to heal
      their esophagitis. Prior to beginning omeprazole (40 mg/day), all patients were
      on H2 antagonists for at least 9 months and still had endoscopic evidence of
      longitudinal (grade II) or circumferential (grade III) distal esophageal
      ulceration. Omeprazole therapy brought about complete endoscopic healing in 24 of
      25 patients (96%). Twenty-three of 24 healed patients were then restarted on H2
      antagonists as maintenance therapy. Repeat endoscopy was performed if symptoms
      recurred. Fourteen of 24 patients (58%) had recurrence of endoscopic esophagitis
      documented between 26 and 300 days from the time of starting maintenance therapy.
      Two of these 14 patients opted for antireflux surgery, whereas the remaining 12
      were once again given omeprazole, which again resulted in symptom resolution in
      all patients. These data suggest that most patients with H2 receptor antagonist
      resistant ulcerative esophagitis cannot be successfully maintained on H2
      antagonists even after the ulcers have been healed with omeprazole. Further
      studies are required to determine the role of omeprazole compared to other
      treatments in the long-term maintenance therapy of these patients.

PMID- 1979986
TI  - Molecular analysis of two recombinant mouse strains with crossovers in the E
      alpha recombination hot spot.
AB  - Recombination in the E alpha gene of the mouse major histocompatibility complex
      has been found to occur only in mice derived from crosses between strains with
      the k and p haplotypes. In the present paper the crossover sites of six
      additional strains were examined by RFLP analysis. These recombinant strains were
      derived from crosses between strains (B10.RPD1, B10.RPD2) with crossovers in the
      E alpha gene and B10.M (H-2f). Four have crossover sites between the E alpha gene
      and the S region. One recombinant (B10.RFD7) also crossed over within the E alpha
      gene and a second (B10.RPF1) crossed over within a segment located to the left of
      the E alpha gene. This study suggests that the DNA sequence responsible for
      recombination in the E alpha gene is also present in the B10.RPD1 and B10.RPD2
      recombinant strains.

PMID- 1979985
TI  - Refractory parastomal ulcers: a multidisciplinary approach.
AB  - Chronic parastomal ulcers in patients with ileostomy or colostomy stomas are
      unusual. Previous reports have implicated infections, fistulas, recurrent
      inflammatory bowel disease (IBD), pyoderma gangrenosum, and trauma. Over the past
      8 years we have evaluated 10 cases of such refractory parastomal ulcers that
      occurred at a mean of 11 years after stomal surgery. Eight patients had had an
      ileostomy for IBD while two had undergone colostomy for colon cancer. Five
      patients with IBD were diagnosed as having pyoderma gangrenosum ulcerations. They
      required systemic treatment for a mean of 25 weeks to effect ulcer healing. The
      other five patients had either parastomal ulcers on the basis of dermatoses
      (contact dermatitis, eczema, or bullous pemphigoid) or contact ulcers due to face
      plate pressure and parastomal dermatitis. These patients received topical
      treatment with healing of ulcers in a mean of 4 weeks. We conclude that
      parastomal ulcers occurring in patients without IBD or IBD patients without
      classic pyoderma gangrenosum require early dermatologic evaluation as they
      respond relatively quickly to appropriate local therapy.

PMID- 1979987
TI  - HLA in juvenile dermatitis herpetiformis: clinical heterogeneity correlated with
      DNA and serological polymorphism.
AB  - A group of 30 Italian children affected by Dermatitis Herpetiformis (DH) was
      analysed for HLA region polymorphisms with both serological and DNA methods.
      Serological typing was performed on HLA-A, B, C, DR, DQ antigens and C4A, C4B, Bf
      polymorphisms. DNA RFLPs obtained with TaqI enzyme were investigated with cDNA
      probes specific for DR beta, DQ alpha and DQ beta genes. The results were
      correlated with intestinal involvement and age at onset of the disease. The
      following observations were made: (1) the intestinal biopsies revealed a direct
      correlation between degree of lesions and age at onset of DH; (2) a significantly
      increased relative risk (RR) was found for the following HLA antigens: A1 (RR =
      2.2), B8 (RR = 6.2), Cw7 (RR = 3.9), C4AQ0 (RR = 7.4), DR3 (RR = 5.2), DR7 (RR =
      4.4), DRw53 (RR = 4.7), DQw2 (RR = 6.0); (3) B8 and DR3 were significantly more
      frequent in patients with severe intestinal lesions; and (4) of the two DR3
      subtypes revealed by RFLP typing, only 3.1 showed an increased frequency in DH
      patients (RR = 8.4). It is suggested that the susceptibility to Juvenile DH is
      determined by the same genes, within the HLA region, that are associated with
      Coeliac Disease.

PMID- 1979988
TI  - [Free internal mammary artery for coronary bypass].
AB  - We studied 12 cases of free internal mammary artery (IMA) grafting. We used IMAs
      as free grafts mainly because of its shortness (6 cases 50%) and injury during
      dissection (4 cases 33%) and found the varicose change of saphenous vein in 5
      cases (42%). Most of the grafting sites are distal parts of coronary arteries.
      Proximal anastomosis sites are other vein grafts (3 cases), other IMA grafts (3
      cases), vein grafts interposing to the aorta (3 cases), and aorta (1 case).
      Patency rate of the free IMA grafts 4 weeks after operations was good (82%). Free
      IMA grafting is safe alternative to in situ IMA grafting when IMA grafts are
      short or injured and saphenous vein grafting is impossible.

PMID- 1979989
TI  - 'Teeth in the neck'.

PMID- 1979990
TI  - Impact of echocardiography on the management of patients with mitral valve
      prolapse.
AB  - OBJECTIVE: To determine whether echocardiography affects the decisions to use
      beta blockers or to recommend bacterial endocarditis prophylaxis in patients
      suspected of having mitral valve prolapse (MVP). DESIGN: Retrospective review of
      echocardiograms and clinical records. SETTING: Military tertiary care hospital.
      PATIENTS: 127 patients with clinically suspected MVP (105) or incidentally
      discovered MVP (22). MAIN RESULTS: Beta blockers were used more often in patients
      with suspected MVP and positive echocardiograms (45%) than in patients with
      normal echocardiograms (13%, p less than 0.001). Bacterial endocarditis
      prophylaxis was recommended more often in patients with suspected MVP and
      positive echocardiograms (65%) than in patients with normal echocardiograms (11%,
      p less than 0.001). Presence or absence of a murmur did not influence the
      decision to recommend bacterial endocarditis prophylaxis. Patients in whom MVP
      was incidentally discovered were unlikely to receive either beta blockers or the
      recommendation for bacterial endocarditis prophylaxis. CONCLUSIONS: The results
      of echocardiography affect the decisions to use beta blockers or to recommend
      bacterial endocarditis prophylaxis in patients with suspected MVP.

PMID- 1979992
TI  - Acute cervico-facial oedema and loss of consciousness following ingestion of
      barracuda fish.
AB  - A young male presented with acute cervico-facial swelling and loss of
      consciousness, following ingestion of barracuda flesh. He recovered after
      administration of anti-histamines and steroids. Toxicity associated with
      barracuda is discussed.

PMID- 1979991
TI  - Pharmacokinetic-pharmacodynamic modeling of the central nervous system effects of
      heptabarbital using aperiodic EEG analysis.
AB  - The concentration EEG effect relationship of heptabarbital was modeled using
      effect parameters derived from aperiodic EEG analysis. Male Wistar rats (n = 10)
      received an intravenous infusion of heptabarbital at a rate of 6-9 mg/kg per min
      until burst suppression with isoelectric periods of 5 sec or longer. Arterial
      blood samples were obtained and EEG was measured continuously until recovery of
      baseline EEG and subjected to aperiodic analysis for quantification. Two EEG
      parameters, the amplitudes per second (AMP) and the total number of waves per
      second (TNW), in five discrete frequency ranges and for two EEG leads were used
      as descriptors of the drug effect on the brain. The EEG parameters responded both
      qualitatively and quantitatively different to increasing concentrations of
      heptabarbital. Monophasic concentration effect curves (decrease) were found for
      the frequency ranges greater than 2.5 Hz and successfully quantified with a
      sigmoidal Emax model after collapsing the hysteresis by a nonparametric modeling
      approach. For the parameter TNW in the 2.5-30 Hz frequency range the value of the
      pharmacodynamic parameters EC50, Emax, and n (means +/- SD) were 78 +/- 7 mg/L,
      11.4 +/- 1.7 waves/sec and 5.0 +/- 1.5, respectively. For other discrete
      frequency ranges, differences in EC50 were observed, indicating differences in
      sensitivity to the effect of heptabarbital. In the 0.5 +/- 2.5 Hz frequency range
      biphasic concentration effect relationships (increase followed by decrease) were
      observed. To fully account for the hysteresis in these concentration effect
      relationships, postulation of two effect compartments was necessary. To
      characterize these biphasic effect curves two different pharmacodynamic models
      were evaluated. Model 1 characterized the biphasic concentration effect
      relationship as the summation of two sigmoidal Emax models, whereas Model 2
      assumed the biphasic effect to be the result of only one inhibitory mechanism of
      action. With Model 1 however realistic parameter estimation was difficult because
      the maximal increase could not be measured, resulting in high correlations
      between parameter estimates. This seriously limits the value of Model 1. Model 2
      involves besides estimation of the classical pharmacodynamic parameters Emax,
      EC50, and n also estimation of the maximal disinhibition Amax. This model is a
      new approach to characterize biphasic drug effects and allows, in principle,
      reliable estimation of all relevant pharmacodynamic parameters.

PMID- 1979993
TI  - Psychotropic drugs and mental retardation: 2. A comparison of psychoactive drug
      use before and after discharge from hospital to community.
AB  - The use of psychoactive medication was examined among 64 people with mental
      retardation who moved from two hospitals to the community as part of a plan of
      resettlement. There was no significant difference between the overall use of
      antipsychotic drugs 2 years before discharge, on the date of discharge and after
      at least 6 months (mean 25 months) of community living, although changes in drugs
      and doses prescribed had taken place. About 39% of people were receiving
      antipsychotics, 32% receiving antiepileptics, 7% receiving antidepressants and 8%
      receiving benzodiazepines.

PMID- 1979994
TI  - Error-prone SOS repair can be error-free.
AB  - Most of the mutagenesis that accompanies the SOS repair of ultraviolet light
      induced lesions in the single-stranded DNA of phage S13 is eliminated when the
      groES or the groEL gene of Escherichia coli is defective. Therefore, this SOS
      mutagenesis is not a necessary consequence of what is commonly called error-prone
      repair, but is additionally imposed on the repair system by the GroE heat shock
      proteins, which are responsible for the assembly of polypeptides into multimeric
      structures.

PMID- 1979995
TI  - [Immunophenotypic analysis of human endothelial cells].
AB  - Very Little is known about the immunological attributes of human endothelial
      cells. In this study, we performed immunologic phenotypic analysis of cultured
      human dermal microvascular endothelial cells in comparison with human umbilical
      vein endothelial cells and examined the ability of various biologic response
      modifiers to alter the phenotypes. Using FACS analysis, both types of the cells
      appear to lack many of the cell surface markers of immunologically proficient
      cells, E.G. OKT4, OKT8, Leu7, FcIgG receptor, complement receptors, IL-2 receptor
      and HLA-Dr, but they possess beta 2-microglobulin and DAF. HLA-Dr antigens can be
      induced on both types of endothelial cells by gamma-IFN in a dose and time
      dependent manner. Both types of endothelial cells possess several kinds of Cell
      Adhesion Molecules (CAMs), such as ICAM-1, CD44, LFA-3, but not LFA-1 or CD2.
      ICAM-1 but not LFA-3 or CD44 can be upregulated by exposure of both types of
      endothelial cells to gamma-IFN, IL-1 and TNF. These data suggest that endothelial
      cells of the dermal microvasculature may play central roles in a variety of
      different cutaneous inflammation.

PMID- 1979996
TI  - Parental origin and mechanism of formation of X chromosome structural
      abnormalities: four cases determined with RFLPs.
AB  - Parental origin and mechanism of formation of X chromosome structural
      abnormalities were studied in one each case of dup(X)(pter----p11.4::p22.1---
      qter), del(X)(qter----p11:), i(X)(qter----cen----qter), and inv dup(X) (pter---
      q22::q22----pter) using various X-linked RFLPs as genetic markers. Segregation
      and densitometric analyses on polymorphic DNAs revealed that the dup(Xp) and the
      del(Xp) are both of paternal origin and the i(Xq) and i dic(X) are of maternal
      origin. The dup(Xp) had arisen by an unequal sister chromatid exchange and the
      del(Xp) had occurred through an intrachromosomal breakage-reunion mechanism, both
      in the paternal X chromosome. The i(Xq) had arisen either through centromere
      fission of a maternal X chromosome, followed by duplication of its long-arm, or
      through a translocation between two maternal X chromosomes after meiotic crossing
      over. The inv dup(X) arose through sister chromatid breakage and reunion in a
      maternal X chromosome. These results, together with those of previous studies,
      suggest that the de novo abnormalities due to events involving centromere
      disruption arise predominantly during oogenesis, while those due to simple
      breakage-reunion events occur preferentially during spermatogenesis.

PMID- 1979997
TI  - Effect of a serotonin blocking agent on renal hemodynamics in the normal rat.
AB  - These studies were designed to explore the effects of ketanserin (K), a
      serotonergic S2-receptor blocker on glomerular filtration rate (GFR), renal
      plasma flow (RPF) and autoregulation of renal blood flow (RBF) in the normal,
      anesthetized rat. Two doses of ketanserin were used: a high dose that, in
      addition to its serotonin blocking effect, possessed alpha 1-adrenergic blocking
      capacities; and a low dose that acted only as a serotonin S2 blocking agent. The
      effects of the high dose were compared to the effects of phenotolamine. Both the
      high dose of K and phentolamine resulted in a similar fall of systemic blood
      pressure from 117 +/- 4 to 78 +/- 3 and from 121 +/- 4.5 to 76 +/- 5 mm Hg,
      respectively (P less than 0.01). Despite this fall, GFR and RPF remained
      unchanged from 2.36 +/- 0.16 +/- to 2.26 +/- 0.12 ml/min, and from 5.33 +/- 0.41
      to 5.76 +/- 0.5 ml/min with K, while both parameters significantly decreased with
      phentolamine. A remarkable preservation of the autoregulation of RBF until a
      renal perfusion pressure (RPP) of 70 to 75 mm Hg was noted with K, but not with
      phentolamine or Ringer infusion. With the low dose of K, a significant rise in
      GFR and PAH clearance was noted, from 2.12 +/- 0.17 to 2.59 +/- 0.18 and from
      4.81 +/- 0.35 to 5.66 +/- 0.48 ml/min, respectively (P less than 0.05). A similar
      preservation of autoregulation of RBF was observed. Our studies suggest that in
      the pressure ranges below normal autoregulation of RBF in the rat, serotonin
      blockade is associated with maintenance of both GFR and RBF.

PMID- 1979998
TI  - Amperozide, a putative anti-psychotic drug: uptake inhibition and release of
      dopamine in vitro in the rat brain.
AB  - The effects of amperozide (a diphenylbutylpiperazinecarboxamide derivative) on
      the uptake and release of 3H-dopamine in vitro were investigated. Amperozide
      inhibited the amphetamine-stimulated release of dopamine from perfused rat
      striatal tissue in a dose-dependent manner. With 1 and 10 microM amperozide there
      was significant inhibition of the amphetamine-stimulated release of dopamine, to
      44 and 36% of control. In contrast, 10 microM amperozide significantly
      strengthened the electrically stimulated release of dopamine from perfused
      striatal slices. Amperozide 1-10 microM had no significant effect on the
      potassium-stimulated release of dopamine. 10 microM amperozide also slightly
      increased the basal release of 3H-dopamine from perfused striatal tissue. These
      effects on various types of release are similar to those reported for uptake
      inhibitors (Bowyer et al, 1984). The uptake of dopamine in striatal tissue was
      inhibited by amperozide with IC50 values of 18 microM for uptake in chopped
      tissue and 1.0 microM for uptake in synaptosomes. Amperozide also inhibited the
      uptake of serotonin in synaptosomes from frontal cortex, IC50 = 0.32 microM and
      the uptake of noradrenaline in cortical synaptosomes, IC50 = 0.78 microM. In
      conclusion, amperozide shows uptake-inhibiting properties in both release and
      uptake studies done in vitro on the rat. In the in vivo studies, however,
      amperozide differs from dopamine uptake inhibitors.

PMID- 1979999
TI  - Direct stimulation of pituitary prolactin release by glutamate.
AB  - The ability of glutamate and other excitatory amino acids to stimulate prolactin
      secretion when administered to adult animals is hypothesized to depend on a
      central site of action in the brain, but there are no data to support this
      position. An alternative hypothesis was tested that glutamate would stimulate
      prolactin release when applied directly to primary cultures of dispersed adult
      female rat anterior pituitary cells studied in a perifusion protocol. Glutamate
      increased the rate of prolactin release within two minutes in a self-limited
      manner. Glutamate-stimulated prolactin release was augmented about 4-fold by
      elimination of magnesium from the perfusate and was associated with stimulation
      of pituitary calcium flux. Ketamine and MK-801 both reduced the basal rate of
      prolactin release and abolished the effects of glutamate. Pituitary cells of 10
      day-old rats responded similarly to glutamate. Exposure to glutamate did not
      influence subsequent responses to physiological hypothalamic secretagogues, thus
      the likelihood of toxicity was minimized. These results suggest that the N-methyl
      D-aspartate (NMDA) subclass of the glutamate receptor complex is involved.
      Prolactin secretion may be regulated physiologically through a functional
      glutamate receptor on pituitary cells.

PMID- 1980000
TI  - Description of a hybridoma bank towards Bordetella pertussis toxin and surface
      antigens.
AB  - This paper describes the development of a murine bank of monoclonal antibodies
      against Bordetella pertussis toxin, filamentous hemagglutinin (FHA), pili,
      lipopolysaccharide (LPS), or outer membrane proteins (OMPs). Subunits S1, S2, S3
      of pertussis toxin (PT) bound immunoglobulins and glycoproteins such as fetuin
      and haptoglobin in an unspecific manner. The specificity of monoclonal antibodies
      towards subunits S1, S2, S3 or S4 of PT could be demonstrated by using purified
      immunoglobulins or their Fab2 fragments. A set of FHA-specific monoclonal
      antibodies could be differentiated on the basis of their binding to the various
      breakdown products present in FHA preparations. Pili-specific monoclonal
      antibodies reacted with either native pili or denatured pilin, and both
      demonstrated serotype specificity. Monoclonal antibodies to Bordetella pertussis
      OMPs were directed to either the virulent phase-regulated trypsin-sensitive,
      detergent-extractable OMPs 92 kDa, 32 kDa, and 30 kDa or the non-virulent phase
      expressed, not-trypsin sensitive OMPs 38 kDa, 33kDa, and 18 kDa.

PMID- 1980001
TI  - Characterization of bovine septicemic, bovine diarrheal, and human enteroinvasive
      Escherichia coli that hybridize with K88 and F41 accessory gene probes but do not
      express these adhesins.
AB  - Certain DNA probes derived from accessory genes of cloned K88 and F41
      determinants hybridize with Escherichia coli strains that express K88 or F41 and
      with certain other E. coli strains that do not express these antigens. We found
      that these probes hybridized with human enteroinvasive E. coli, and with bovine
      E. coli isolates which produced a fatal septicemia in experimentally infected
      piglets. These strains did not hybridize with probes derived from the structural
      subunit genes encoding the K88 and F41 antigens. E. coli strains isolated from
      turkeys with septicemia, Shigella and Salmonella strains did not hybridize to the
      K88 and F41 accessory gene probes. The K88 and F41 accessory genes probes
      hybridized with a 200 kb plasmid which is required for invasion by human
      enteroinvasive E. coli. The K88 and F41 accessory gene homology in the bovine
      isolates was located on a 150 kb transmissible plasmid but was unrelated to
      plasmids encoding aerobactin, Vir, or colicin V, which are suspected virulence
      factors in septicemic E. coli. A common plasmid-encoded antigen was associated
      with bovine isolates that hybridized with the K88 and F41 accessory gene probes.
      This included strains which express CS31A, a surface antigen associated with
      bovine septicemic E. coli, which also hybridized with the K88 and F4 accessory
      gene probes. The results suggest that the K88 and F41 accessory gene probes
      hybridized with sequences that may be associated with a common mechanism of pilus
      expression in distinct groups of E. coli pathogens.

PMID- 1980003
TI  - Regulation of branched-chain amino acid biosynthesis in Neurospora crassa:
      cloning and characterization of the leu-1 and ilv-3 genes.
AB  - The genes coding for the branched-chain amino acid biosynthetic enzymes comprise
      an integrated regulatory system. The expression of the several structural genes
      coding for enzymes of the isoleucine-valine and leucine pathways is controlled in
      parallel by the positive-acting regulatory gene, leu-3. The leu-1 and ilv-3
      genes, coding for beta-isopropyl-malate dehydrogenase and aceto-hydroxyacid
      synthase, respectively, were cloned from a cosmid library. Restriction fragment
      length polymorphism analysis revealed that the two cloned fragments indeed mapped
      to the genomic locations of the leu-1 and ilv-3 genes, respectively. Northern
      blot analysis demonstrated that the leu-1 gene is transcribed to give an mRNA of
      approximately 1.5 kb, whereas the ilv-3 transcript size is 2.6 kb. The expression
      of both genes appears to be regulated at the transcriptional level. One leu-3
      regulatory mutant was greatly deficient in both leu-1 and ilv-3 mRNAs, whereas
      another leu-3 allele showed an unusual antiparallel pattern of regulation.

PMID- 1980002
TI  - Aspartokinase genes lysC alpha and lysC beta overlap and are adjacent to the
      aspartate beta-semialdehyde dehydrogenase gene asd in Corynebacterium glutamicum.
AB  - A 2.1 kb DNA fragment of the recombinant plasmid pCS2, isolated from an
      aminoethyl cysteine (AEC)-resistant and lysine-producing Corynebacterium
      glutamicum mutant strain, and which confers AEC resistance and lysine production
      on the wild-type G. glutamicum ATCC 13032 was analysed. DNA sequence analysis of
      this fragment revealed three large open reading frames (ORFs). The incomplete
      ORF1 does not contain the 5' end of the coding region. ORF2, which uses the same
      reading frame as ORF1, is identical to the 3' end of ORF1 and encodes a putative
      protein of 172 amino acids (aa) and of Mr 18,584. ORF3 encodes a putative protein
      of 344 aa and of Mr 36,275. The amino acid sequences deduced from ORF1 and ORF2
      display strong homologies to those of the alpha- and beta-subunits of the
      Bacillus subtilis aspartokinase II. It is therefore proposed that the incomplete
      ORF1, termed lysC alpha, encodes part of the alpha-subunit of the C. glutamicum
      aspartokinase whereas the complete ORF2, termed lysC beta, encodes the beta
      subunit of the same enzyme. ORF2 is responsible for AEC resistance and lysine
      production due to a feedback-resistant aspartokinase. The amino acid sequence
      deduced from ORF3, termed asd, is highly homologous to that of the Streptococcus
      mutans aspartate beta-semialdehyde dehydrogenase (ASD). Plasmids carrying the C.
      glutamicum asd gene complemented Escherichia coli asd mutants. Increase in ASD
      activity by a factor of 30-60 was measured for C. glutamicum cells harbouring
      high copy-number plasmids with the C. glutamicum asd gene.

PMID- 1980005
TI  - Cellular fatty acid-binding proteins. First International Workshop on Fatty Acid
      Binding Proteins. Maastricht, The Netherlands, September 4-5, 1989. Proceedings.

PMID- 1980004
TI  - Elicitor-specific induction of one member of the chitinase gene family in Arachis
      hypogaea.
AB  - Chitinases are believed to play an important role in plant defence against
      bacterial and fungal attack. In peanut (Arachis hypogaea) chitinase genes form a
      small multigene family. Four chitinase cDNAs (chit 1-4) were isolated from
      cultured peanut cells. Expression of individual chit genes was assayed by the
      polymerase chain reaction (PCR) followed by analysis of restriction fragment
      length polymorphisms (RFLP). UV irradiation, dilution of cell cultures and
      treatment with Phytophthora megasperma (Pmg) elicitor or yeast extract were used
      to induce expression of chit genes. The chit 3 gene is constitutively expressed
      at a low level in untreated as well as in treated cultures; the expression of
      chit 4 gene is induced by each of the stimuli tested, whereas the chit 1 gene is
      activated by cell culture dilution and by yeast extract treatment. The chit 2
      gene is strongly activated by treatment with cell wall components from the fungus
      Phytophthora megasperma but not by the other stimuli. These results indicate that
      chit 2 gene expression may be controlled by pathogen-specific regulatory
      elements.

PMID- 1980006
TI  - pHAZE: a shuttle vector system for the detection and analysis of ionizing
      radiation-induced mutations.
AB  - We have designed and constructed a shuttle vector system, pHAZE, that is
      maintained as an episome in normal human fibroblasts, has a low background
      mutation frequency, and is capable of detecting a spectrum of mutations,
      including deletions up to 8.3 kb. The efficacy of this system was demonstrated by
      using it to analyze mutations produced by X-rays, which induced both point
      mutations and large deletions in pHAZE.

PMID- 1980007
TI  - Preferential loss of maternal alleles in sporadic Wilms' tumour.
AB  - Loss of heterozygosity at loci on the short arm of chromosome 11 has been
      reported in 31% (11/38) of Wilms' tumours in our series. Lymphoblastoid cell
      lines were prepared from the parents of 10/11 of the patients showing allele loss
      in their tumours. In 9 of the cases, where the parental origin of the alleles
      could be followed, it was the paternal alleles which were retained in the tumour.
      This preferential loss of the maternal alleles implies a role for genomic
      imprinting in the pathogenesis of Wilms' tumour.

PMID- 1980009
TI  - First-line management of sinusitis: a national problem? Palm Beach, Florida,
      April 27, 1990. Proceedings.

PMID- 1980008
TI  - Restriction fragment length polymorphisms in the rat N-ras and retinoblastoma
      genes: their identification and characterization.
AB  - We have observed restriction fragment length polymorphisms for the N-ras and
      retinoblastoma (Rb) genes between rat strains that are susceptible or resistant
      to induction of pituitary tumors by diethylstilbestrol (DES). Thirteen other
      proto-oncogenes tested displayed the same restriction patterns between all
      samples. The N-ras polymorphism is observed with more than one restriction
      nuclease and the N-ras and Rb polymorphisms are not a result of DES treatment.
      The N-ras polymorphism is inherited in a Mendelian fashion and there appear to be
      two separate loci in the rat genome that are detected by the N-ras probe. For
      both the N-ras and Rb genes there is an 'extra' fragment in the tumor-resistant
      animals that is not seen in the susceptible rats. These polymorphisms may
      indicate regions of the genome that play a role in determining susceptibility to
      pituitary tumors or any of a number of other chemically induced tumors.

PMID- 1980010
TI  - Thirteenth European Conference on Visual Perception. Paris, France, 4-7 September
      1990. Abstracts.

PMID- 1980011
TI  - What every family and community has a right to know about malaria.

PMID- 1980012
TI  - Localized neuropathy following jellyfish sting.
AB  - This report describes the case of an 18 year old female who sustained a jellyfish
      sting on her right wrist. She subsequently developed complete radial, ulnar and
      median nerve palsies distal to the site of the sting, which recovered fully over
      the next 10 months. We believe this to be due to a direct neurotoxic effect of
      the jellyfish venom.

PMID- 1980013
TI  - [Sleep disorders related to anxiety].
AB  - Sleep disorders related to depressive illness are now well documented. However,
      sleep disturbances associated with anxiety have only been explored in recent
      time. All types of anxiety (generalized anxiety, obsessive-compulsive disorders,
      panic attack) are associated with sleep disorders such as early insomnia, sleep
      interruption and low efficiency of sleep. The EEG approach gives different
      results according to the type of anxiety. Generalized anxiety is associated with
      total sleep time reduction and low efficiency of sleep. Sleep is unstable with
      numerous awakenings. Longer periods of stage 1 and 2 sleep are observed and slow
      wave sleeps as well as REM sleep time is reduced. REM sleep latency may be
      reduced in obsessive compulsive disorders. Although sleep abnormalities observed
      in anxiety disorders differ from those observed in depressive disorders, none of
      these features can be considered specific of anxiety.

PMID- 1980014
TI  - [Evolution of the definition of AIDS. The main classifications of HIV infection].
AB  - The purpose of this paper is to trace the evolution of AIDS definition and
      describe the principal classification systems of HIV infection as defined since
      1981. Our work is principally based on data from the American Centers of Disease
      Control on the one hand (clinical evaluation of infection stage) and from the
      Walter Reed Institute (immunological evaluation of infection stage) on the other
      hand. To describe this disease with multiple aspects the separate use of these
      two classification systems does not provide a thorough evaluation of the
      patient's condition. Non consensus had been reached to date, although an
      agreement on this matter would foster an important epidemiological and
      therapeutic progress in both adult and childhood patients.

PMID- 1980015
TI  - [Effects and side effects of depot neuroleptics as perceived by patients].
AB  - A relatively wide acceptance of neuroleptic depot medication was seen among the
      patients of a large psychiatric hospital on the occasion of a survey conducted on
      a randomly chosen day. Patients described their experience of undesirable side
      effects. A basic common trait of disturbances of the feeling tone caused by depot
      neuroleptics was the simultaneous occurrence of conflicting emotions. Complaints
      by patients treated with depot neuroleptics about undesirable side effects can
      thus be better differentiated from their experience of the underlying psychotic
      disease and certain forms of experience that are typical of the personality
      concerned.

PMID- 1980016
TI  - Two-tier diagnosing in psychiatry.
AB  - This article addresses the question: what is the most productive way to
      systematize abnormal behavior in order to study its biological roots? Though
      nosology still occupies the premier position in biological psychiatry, it is, in
      and by itself, a treacherous beacon. Syndromal organization of psychopathology is
      likewise seriously flawed. A functional organization of psychopathology is
      considered the most appropriate framework for biological research and a plea is
      made for a two-tier diagnostic system of psychiatric disorders. Tier one
      comprises the nosological diagnosis, and tier two a detailed depiction of the
      component psychological dysfunctions. Such a two-tier diagnostic system would
      bring psychopathology onto a true scientific footing.

PMID- 1980017
TI  - Skin conductance responding in schizophrenic patients with abnormal involuntary
      movements.
AB  - The present study tested the hypothesis that neuroleptic treatment modifies the
      skin conductance response (SCR) to loud tones. Schizophrenic patients with and
      without drug-induced abnormal involuntary movements were tested before and after
      drug withdrawal. During the on-drugs session, habituation of SCR correlated with
      the daily neuroleptic dose, and patients with tardive dyskinesia (TD) showed the
      fastest habituation of SCR. These findings were interpreted as indicating that
      SCR is attenuated by neuroleptics present during the examination and that TD
      patients demonstrate a preferential susceptibility to this effect. Withdrawal of
      medication resulted in slowing of SCR habituation only in TD patients, following
      which the entire sample showed a similar rate of habituation. These findings
      suggest that accelerated SCR habituation is not a stable trait of TD patients.

PMID- 1980018
TI  - Cholinergic neurotransmission: functional and clinical aspects. Proceedings of
      Nobel Symposium 76. Lidingo Island, Stockholm, August 1989.

PMID- 1980019
TI  - Implications of multiple transmitter system lesions for cholinomimetic therapy in
      Alzheimer's disease.

PMID- 1980020
TI  - Neuropharmacology of amyotrophic lateral sclerosis.

PMID- 1980021
TI  - Spontaneous synaptic activity at developing neuromuscular junctions.

PMID- 1980022
TI  - [Regional differences in drug use in relation to the causes].
AB  - The purpose of the study was in comparison of drug use in the treatment of
      coronary disease or hypertension in the random selected representative population
      sample of Warsaw and Tarnobrzeg province . In the study women and men aged 35 to
      64 years were included according to POL-MONICA studies. Among 2646 subjects
      studied in Warsaw 23% used drugs whereas among 2722 subjects from the Tarnobrzeg
      province the drug users represented 12.1%. The most frequently used drugs in the
      treatment of coronary disease were nitrates, curantyl and beta-blockers. The drug
      use in subjects with coronary disease (DDD/1000 inhabitants/day) was 4.5-fold
      higher in Warsaw than in the Tarnobrzeg province . The most frequently drug used
      in treatment of hypertension in Warsaw were beta-blockers and diuretics, whereas
      in the Tarnobrzeg province among men diuretic and composed drug preparations;
      women in the last region used frequently composed drug preparations and smooth
      muscle relaxants. The relationship between the use of particular drug groups and
      the region was significant in women. The hypotensic drug use in Warsaw was twice
      as high as in the Tarnobrzeg voivodship despite similar frequency of hypertension
      in both regions.

PMID- 1980024
TI  - [Treatment of Wolff-Parkinson-White syndrome associated with asthma].
AB  - We performed division of accessory pathways in five asthma patients associated
      with Wolff-Parkinson-White (WPW) syndrome, for whom the administration of a beta
      blocker for the tachycardia is contraindicated, and the administration of
      bronchodilators for the asthma attack may cause premature ventricular
      contractions. As a result, the tachycardic attacks disappeared postoperatively,
      both at rest and following administration of bronchodilators. Radical treatment
      of WPW syndrome by division the accessory pathway is considered to be necessary
      for the safe treatment of asthma.

PMID- 1980023
TI  - Helodermin, but not cholecystokinin, somatostatin, or thyrotropin releasing
      hormone, acutely increases thyroid blood flow in the rat.
AB  - In the present study, we investigated whether peptides located within the thyroid
      gland, but not directly found in nerve fibers associated with blood vessels,
      might influence thyroid blood flow. Specifically, we evaluated the effects of
      helodermin, cholecystokinin (CCK), somatostatin (SRIF) and thyrotropin releasing
      hormone (TRH) given systemically on thyroid blood flow and circulating thyroid
      hormone levels. Blood flows in the thyroid and six other organs were measured in
      male rats using 141Ce-labeled microspheres. Circulating thyrotropin (TSH) and
      thyroid hormone levels were monitored by RIA. Helodermin (10(-10) mol/100 g BW,
      i.v. over 4 min) markedly elevated thyroid blood flow (52 +/- 6 vs. 10 +/- 2
      ml/min.g in vehicle-infused rats; n = 5). Blood flows to the salivary gland,
      pancreas, lacrimal gland and stomach (but not adrenal and kidney) were also
      increased during helodermin infusions. CCK, SRIF, and TRH were without effect on
      blood flows to the thyroid and other organs even though these peptides were
      tested at higher molar doses than helodermin. Helodermin, CCK, or SRIF did not
      affect thyroid hormone or plasma calcium levels. As expected however, plasma TSH
      and T3 levels were increased at 20 min and 2 h, respectively, following TRH
      infusions. Since helodermin shares sequence homology with VIP, we next compared
      the relative effects of these two peptides on thyroid and other organ blood
      flows. VIP (10(-11) mol/100 g BW, i.v.) was more potent in increasing blood flows
      to the thyroid, salivary gland, and pancreas than an equimolar dose of
      helodermin. This study shows that while helodermin, like VIP, has the ability to
      increase thyroid and other organ blood flows, it appears to be a less potent
      vasodilator.

PMID- 1980025
TI  - [Regular inhalation therapy with antiasthmatic agents].

PMID- 1980026
TI  - [Preliminary report on the effect of low doses of azidothymidine (AZT) in the
      treatment of patients with stage III infection by human immunodeficiency virus
      (HIV)].
AB  - Ten patients with CDC stage III of infection by HIV were treated with AZT at
      doses of 300 mg/day (100 mg tid). There were 5 males and 5 females, the median
      age being 40.5 yr' (range 26-46). Seventy percent of them had transfusion
      associated HIV infection and the rest had been infected by the sexual route. A
      positive clinical response was observed in 100% of the group after 16-24 weeks of
      treatment: the Karnofsky performance status increased from 64% to 94% (p less
      than 0.01), the white blood cell count raised from 3.7 to 6.0 K/microL (p less
      than 0.01), the number of helper lymphocytes (CD4+) also raised significantly
      from 248.2 to 470.7/uL (p less than .01). Only two patients required red blood
      cells transfusions. The life expectancy at 82 weeks was 90%. Toxicity was both
      moderate and transitory. It is concluded that low doses of AZT (300 mg/day)
      produce similar clinical results as doses of 1200-1500 mg/day. A larger study is
      needed to support our preliminary findings.

PMID- 1980027
TI  - [Clinical comparison of butamirate citrate with a codeine-based antitussive
      agent].

PMID- 1980028
TI  - Nursing the mind. Minimizing adverse drug reactions.

PMID- 1980029
TI  - [The function of beta receptors in chronic left ventricular insufficiency].
AB  - Hyperactivity of the noradrenergic sympathetic system is one of the essential
      "compensatory"mechanisms in chronic left ventricular failure. The ensuing
      stimulation of myocardial beta-adrenergic receptors results in an increase of
      heart rate and contractility which, to some extent, counterbalances the
      alteration of left ventricular function, but rapidly reaches its limits: the
      excessive shortening of diastoles and, mostly, the increase of myocardial oxygen
      demand neutralize the beneficial haemodynamic effect of beta-adrenergic
      stimulation, especially when ischaemia is the cause of the heart failure; the
      chronic exposure of adrenergic receptors to noradrenaline in high concentrations
      leads to desensitization, to a "down regulation" which primarily affects the beta
      1 receptors and spares, at least partly, the myocardial beta 2 receptors which
      seem to play a quantitatively important inotropic role, particularly in chronic
      heart failure. These new data on the physiology of the cardiac noradrenergic
      system have major therapeutic consequences: in practice, the positively inotropic
      beta-stimulants can only be used for a short period in acute episodes of heart
      failure; - the use of beta-blockers in low doses is now considered in the
      treatment of some forms of heart failure; the mechanism of their therapeutic
      action remains controverted, and their long-term effectiveness in a large patient
      population is under study; - a new pharmacological class, beta-adrenoceptor
      partial agonists, seems to give satisfactory clinical and haemodynamic results in
      mode-rate heart failure, A wider clinical evaluation is needed to determine the
      therapeutic role of theses new pharmacodynamic agents.

PMID- 1980031
TI  - Thalidomide induced alteration in secondary structure of rat embryonic DNA in
      vivo.
AB  - Teratogenicity of thalidomide was demonstrated in Wistar rats following a single
      maternal intravenous injection during the embryonic organogenetic period. When
      compared to day 13 embryonic DNA isolated from untreated control mothers,
      differences were observed in the mean wet weights of day 13 embryos from rats
      treated with thalidomide during days 10 or 11 of gestation, and significantly
      less amounts of embryonic DNA were recovered from mothers similarly treated on
      days 10 or 12 of their respective gestation periods. Rat embryonic DNA may be
      separated into two fractions by stepwise elution from benzoylated DEAE-cellulose
      (BD-cellulose) columns with 1.0 M NaCl (SE-DNA) and 1.8% (w/v) caffeine (CE-DNA)
      solutions, respectively. Other studies using bacterial, yeast, and rat liver DNA
      suggested that the first fraction contains native DNA, whereas the second may
      exhibit some degree of single-stranded character. Similar reproducible
      chromatographic profiles were obtained using a novel "batch method" developed for
      general application. Rat embryonic DNA was monitored by labelling in vivo with an
      i.p. injection of [methyl-3H]-thymidine (3H-TdR) during days 5, 6, and 7 of the
      gestation period. All samples were analysed on day 13 of gestation. A simple
      increase in percentage of caffeine-eluted DNA was not detected in thalidomide
      treated samples; however, diversity of percent (%) CE-DNA within litter was
      noted. Briefly, the percent CE-DNA values for embryos in one litter were ranked
      and arbitrarily grouped in classes with limits of mean +/- 1 SD, mean +/- 2 SD,
      and so on to generate a characteristic profile of percent CE-DNA distribution.
      The number of embryos within the range of each SD unit was expressed as a
      percentage of each litter. A plot of the ranges of percent CE-DNA versus
      percentage of each litter was used to illustrate the distribution profile of the
      particular litter and to be used for comparison between samples from untreated
      control and thalidomide and/or dimethylformamide (DMF) treated DNA. Treatment of
      day 12 mothers with thalidomide produced a majority of embryos having percent CE
      DNA values similar to those of untreated controls with the exception of the
      inclusion of a second population of embryos with much higher percent CE-DNA
      values than those of the untreated controls. Similar treatment of day 11 animals
      produced a majority of embryos still having percent CE-DNA values similar to
      those of untreated controls and also having a second group of embryos with a
      lower percent CE-DNA values than those of untreated controls.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 1980030
TI  - The serotonin receptor subtype 2 locus HTR2 is on human chromosome 13 near genes
      for esterase D and retinoblastoma-1 and on mouse chromosome 14.
AB  - Serotonin (5-hydroxytryptamine) functions as a neurotransmitter and a hormone.
      Its diverse actions are mediated by at least seven distinct cell surface receptor
      subtypes. The serotonin receptor subtype 2 (gene symbol HTR2) is a G-protein
      coupled receptor, expressed primarily in the cerebral cortex, where upon
      stimulation it stimulates the hydrolysis of inositol phospholipids. We have
      mapped the HTR2 locus to human chromosome 13 and to mouse chromosome 14 by
      somatic cell hybrid analysis. Linkage studies in CEPH families, using a PvuII
      RFLP detected with the HTR2 probe, revealed tight linkage between HTR2 and ESD,
      the locus for esterase D. The most likely position for HTR2 is between ESD and
      RB1, the retinoblastoma-1 gene. The homologous loci in mouse, Rb-1 and Esd(Es-10)
      are on mouse chromosome 14, close to ag, agitans, a recessive neurological
      mutation. Having mapped Htr-2 to mouse chromosome 14, we predict that it falls
      into this known conserved gene cluster.

PMID- 1980032
TI  - Induction of sister chromatid exchanges with hypotonic treatment.
AB  - Hypotonic NaCl solutions and diluted culture medium were tested for induction of
      sister chromatid exchanges (SCEs) and chromosomal aberrations (CA). Hypotonic
      treatment conditions were found to induce high frequencies of CA and SCEs.
      However, an increase in SCEs was observed only in cells that also had CA.
      Possible lesions and mechanisms leading to SCEs and CA are discussed.

PMID- 1980033
TI  - Simultaneous induction of mutagenic and cancerogenic effects in T x HT mice with
      transplacental ethylnitrosourea treatment.
AB  - The relationship between mutagenesis and carcinogenesis was investigated in T x
      HT crossbred mice using diaplacental application of ethylnitrosourea (ENU) at
      different stages of embryonal development. Mutagenesis was detected by induction
      of coat color spots, and the carcinogenic response was investigated in a long
      term follow-up study of the F1-generation. The animals were particularly
      sensitive to induction of tumors at the central nervous system (CNS)
      skull/vertebra interface (30% and 20% in ENU-treated male and female offspring,
      respectively, compared with less than 1% in controls). There was a correlation
      between the appearance of these tumors and the presence of color spots. This
      correlation was low but statistically significant in female offspring. Three
      other types of tumors showed a correlation with the presence of coat color spots.
      Liver tumors were significantly increased in color spot-positive females but
      unchanged in males. Lung tumors were reduced in color spot-positive males and
      appeared earlier in color spot-positive females. There was a lower incidence of
      lymphoma/leukemia in all spot-positive mice. The reduction in tumor incidence
      beyond the spontaneous rate in spot-positive animals might be caused by a high
      cytolethal response to ENU in the relevant organs and tissues.

PMID- 1980034
TI  - Effects of alkylating antineoplastics alone or in combination with 3
      aminobenzamide on genotoxicity, antitumor activity, and NAD levels in human
      lymphocytes in vitro and on Ehrlich ascites tumor cells in vivo.
AB  - Enhanced cytogenetic damage by the homo-aza-steroidal ester of p-bis(2
      chloroethyl)-aminophenylacetic acid (ASE) was observed when human lymphocytes in
      vitro or Ehrlich ascites tumor (EAT) cells in vivo were exposed to nontoxic
      concentrations of 3-amino-benzamide (3-AB). 3-AB at these concentrations was
      found to enhance synergistically the cytogenetic damage induced in vivo by
      cyclophosphamide (CP), a metabolically activated chemotherapeutic, or
      chlorambucil (CBC) in EAT cells. One hour before i.p. injection of 5
      bromodeoxyuridine (BrdUrd) adsorbed to activated charcoal, EAT-bearing mice
      treated i.p. with ASE or CP showed a dose-dependent increase in sister chromatid
      exchange (SCE) rates and cell division delays. The treatment of human lymphocytes
      in vitro with ASE led to the depletion of cellular NAD, and addition of 3-AB, a
      potent inhibitor of poly(ADP-ribose)polymerase [P(ADPR)polymerase], to ASE
      treated human lymphocytes prevented the drop of NAD, which remained at
      approximately control levels. Also, the in vivo treatment of EAT cells with CBC,
      ASE, or CP led to the depletion of NAD, whereas addition of 3-AB to CBC-, ASE- or
      CP-treated cells prevented the drop of NAD, which remained at nearly control
      levels. 3-AB in conjunction with CBC, ASE, or CP increased the survival time of
      the EAT-bearing mice and markedly reduced the ascitic volume. Thus cytogenetic
      damage induced by ASE plus 3-AB in vitro and by CBC, ASE, or CP plus 3-AB in vivo
      correlates well with 1) the prevention of NAD depletion in the presence of 3-AB
      in cells treated with the same alkylating agents in vitro or in vivo and 2) the
      in vivo antitumor effect by ASE, CBC, or CP in combination with 3-AB.

PMID- 1980035
TI  - Effects of quercetin, a plant flavonol, on the two-stage transformation in vitro.
AB  - Quercetin was examined for the effects on the two-stage chemical transformation
      of BALB/3T3 cells. Quercetin showed initiating action to induce transformation in
      the cells which were treated with quercetin and subsequently with 0.49 microM 12
      O-tetradecanoyl-phorbol-13-acetate (TPA). Both the proportion of dishes with
      transformed foci and the average number of foci per dish increased with the
      concentration of quercetin (15-45 microM). However, initiating treatment with
      quercetin did not induce transformation without subsequent TPA treatment.
      Quercetin inhibited the promotion caused by 0.49 microM TPA in the transformation
      initiated by 1.9 microM 2-methylcholanthrene (MCA). The inhibitory effect of 30
      microM quercetin was 56% in the number of foci per dish. Thus quercetin was found
      to have initiating effect on the transformation of BALB/3T3 cells, but to
      restrain the promotion by TPA.

PMID- 1980036
TI  - Mutagenic and teratogenic effects of cyclophosphamide on the chick embryo:
      chromosomal aberrations and cell proliferation in affected and unaffected
      tissues.
AB  - Chromosomal aberrations and cell proliferation were analyzed in the chick embryo
      blood, limb bud, and facial tissues 12 and 24 hours after cyclophosphamide (CP)
      administration on day 3. The cytogenic findings were compared with teratogenic
      effects evaluated on incubation day 8. Low dose (0.3 micrograms) resulting in
      heart defects exclusively, increased the frequency of aberrant cells with
      simultaneous depression of cell proliferation in blood only. High dose of CP (6
      micrograms), besides the heart defects, also induced facial clefts and limb
      malformations, and strong clastogenic effects associated with mitotic inhibition
      were observed in all tissues investigated. The results support the idea that the
      consequences of mutagenic action of cyclophosphamide--cell cycle delay and
      excessive death of cells with unstable aberrations--result in abnormal
      morphogenesis.

PMID- 1980037
TI  - Image analysis and mathematical correlation between cell number and diameter of
      colonies in soft agar as a measurement of growth in soft agar.
AB  - Automated image analysis was used to measure the colony diameter and estimate the
      cell number in colonies under conditions for anchorage-independent growth (AIG).
      The calculated values for the number of AIG cells in a colony of a diameter
      greater than or equal to 60 microns were decidedly different from the actual
      values obtained by either automated or manual cell counting. Like animal cells
      that exhibit AIG, these colonies demonstrating anchorage independence can be
      enumerated reproducibly. However, the assumption is incorrect that the number of
      cells (N) in a colony expressing AIG varies directly with a change in the
      diameter of a colony (d). Whether one counts the number of cells manually in a
      colony of a definite diameter or arbitrarily uses a diameter function of greater
      than or equal to 60 microns as a linear distance that indicates the presence of
      50 or more cells in a colony, each procedure has its own built-in bias. In
      procedures that require quantitative data, the most reliable procedure is to
      standardize the values for diameter of colonies with cell numbers in colonies.

PMID- 1980038
TI  - Species differences in renal gamma-glutamyl transpeptidase activity do not
      correlate with susceptibility to 2-bromo-(diglutathion-S-yl)-hydroquinone
      nephrotoxicity.
AB  - Administration of 2-bromo-(diglutathion-S-yl)hydroquinone (2-Br-[diGSyl]HQ) (10
      30 mumol/kg; i.v.) to rats causes severe renal proximal tubular necrosis. gamma
      Glutamyl transpeptidase (gamma-GT) catalyses the first step in the metabolism of
      glutathione (GSH) and its S-conjugates and the toxicity of 2-Br-(diGSyl)HQ can be
      emeliorated by inhibition of renal gamma-GT. Species differences in the specific
      activity of renal gamma-GT have been reported and we now describe the
      relationship between renal gamma-GT and species differences in susceptibility to
      2-Br-(diGSyl)HQ nephrotoxicity. Although rats exhibited the highest specific
      activity of renal gamma-GT, and were the most sensitive species toward 2-Br
      (diGSyl)HQ-mediated nephrotoxicity, renal gamma-GT activity did not correlate
      with susceptibility in the other species examined. Indeed, the guinea pig, which
      expressed the lowest activity of renal gamma-GT between the species (8% of the
      rat) was the only other rodent found to be responsive toward 2-Br-(diGSyl)HQ at
      the highest dose tested (200 mumol/kg; intracardiac). Thus, factors other than
      gamma-GT activity probably play an important role in modulating species
      susceptibility to 2-Br-(diGSyl)HQ nephrotoxicity. Although the reason(s) for the
      interspecies variation in response to 2-Br-(diGSyl)HQ are unclear at present, it
      seems possible that differences in both renal biochemistry, such as differences
      in the relative activities of cysteine conjugate N-acetyl transferase and
      deacetylase, and renal physiology, contribute to the observed results.

PMID- 1980039
TI  - Intracerebral grafting of genetically modified cells acting as biological pumps.

PMID- 1980040
TI  - Novel anxiolytics that act as partial agonists at benzodiazepine receptors.
AB  - Benzodiazepines in clinical use have a range of pharmacological activities. Some,
      e.g. sedation, tolerance and addiction, are not welcome. Undesirable side-effects
      of drugs are often controlled by developing compounds that bind more selectively
      to one particular receptor subtype. An alternative approach, discussed here by
      Willy Haefely and colleagues, is the development of partial agonists which
      exploit regional differences in receptor reserve to tease apart biological
      responses. Partial agonists for the benzodiazepine modulatory site on the GABAA
      complex have been developed and their pharmacological profiles can be interpreted
      to suggest that neurons mediating anticonvulsant and anti-anxiety effects do
      indeed have a higher receptor reserve than neurons mediating other unwanted
      effects. This suggests that benzodiazepine receptor partial agonists may have
      important therapeutic potential.

PMID- 1980041
TI  - The release and uptake of excitatory amino acids.
AB  - In this article, David Nicholls and David Attwell describe recent advances in our
      understanding of the mechanisms by which excitatory amino acids are released from
      cells, and of the way in which a low extracellular glutamate concentration is
      maintained. Glutamate can be released from cells by two mechanism: either by
      Ca2(+)-dependent vesicular release or, in pathological conditions, by reversal of
      the plasma membrane uptake carrier. The contrasting pharmacology and ionic
      dependence of the glutamate uptake carriers in the vesicle membrane and in the
      plasma membrane explain how glutamate (but probably not aspartate) can function
      as a neurotransmitter, and why the extracellular glutamate concentration rises to
      neurotoxic levels in brain anoxia.

PMID- 1980042
TI  - [Disorders and correction of lung functions in acute destructive cholecystitis].
AB  - On the day of operation for acute destructive cholecystitis functions of external
      ventilation prove to be disturbed due to deterioration of pulmonary blood flow (2
      6 times) and ventilation (1.3-3 times). The degree of these disturbances are in
      direct dependence on the degree of the inflammatory process in gallbladder and
      time of preoperative observation. At the same terms after emergency
      cholecystectomy the lung functions were reestablished considerably quicker and
      was more valuable than after operations on urgent indications. Inclusion of
      adrenoblocking agents into conservative treatment of acute cholecystitis before
      and after operation facilitates more effective and quicker recovery of lung
      functions.

PMID- 1980043
TI  - [Orchiopexy in children].

PMID- 1980044
TI  - [Lectures presented at the International Conference on Medicine in a Catastrophe.
      Moscow, May 22-24, 1990].

PMID- 1980045
TI  - [Hantaan virus serotypes circulating in foci of the Far Eastern region of the
      USSR].
AB  - Studies on serodifferentiation by indirect immunofluorescence antibody method and
      neutralization test of Hantaan virus strains isolated from human patients and
      rodents revealed circulation on the Maritime Territory of 5 virus serotypes and
      demonstrated that rodents of one species could be virus carriers of different
      virus serotypes. On the basis of the antigenic similarity of strains isolated
      from human patients, field mice, and Clethrionomys rufocanus it is concluded that
      the virus serotypes circulating among rodents of these species may play a role in
      the etiology of cases of hemorrhagic fever with renal syndrome.

PMID- 1980046
TI  - A critical review of the medical treatment of portal hypertension.
AB  - There are three distinct phases during which treatment might influence the
      outcome in patients with portal hypertension and variceal bleeding: treatment of
      the active bleeding episode, the prevention of recurrent haemorrhage and perhaps
      most controversially the use of prophylactic therapy to avert the first bleeding
      episode. For the treatment of active haemorrhage injection sclerotherapy is
      almost certainly the treatment of choice when the expertise is available. In the
      absence of such, vasoconstrictor therapy continues to be widely adopted as a
      temporizing measure. The efficacy of vasopressin as a single agent has been
      limited by associated cardiovascular complications. The addition of nitroglycerin
      to a vasopressin regime has recently been shown to reduce such complications and
      to improve overall efficacy. Somatostatin represents an alternative
      vasoconstrictor with increasing evidence of efficacy in the absence of serious
      complications. Long-term injection sclerotherapy is widely accepted as the first
      line treatment to prevent recurrence of variceal haemorrhage although early
      rebleeding, prior to the obliteration of varices, represents an important
      limitation of therapy. Alternative local endoscopic therapy using tissue
      adhesives or banding of varices are under evaluation. The major claims of benefit
      initially attributed to oral propranolol for the prevention of rebleeding have
      now been considerably modified and a specific role remains to be defined. Both
      injection sclerotherapy and B-adreno-receptor have been proposed as prophylactic
      therapy to prevent the first variceal haemorrhage. Two extremely positive reports
      of prophylactic sclerotherapy have received little further support and there are
      now few protagonists of this approach.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1980047
TI  - Adrenergic influence on bile secretion--an experimental study in the cat.
AB  - The influence on bile secretion of electrical stimulation of the splanchnic
      nerves and arterial infusion of adrenergic agonists was studied in anaesthetized
      cats. The bile salt secretion was supported by a continuous intravenous infusion
      of sodium glycocholate. Electrical stimulation of the splanchnic nerves reduced
      the volume outflow of bile from 0.71 to 0.44 ml h-1 kg-1 body wt and raised the
      bile acid concentration in bile, while the bile salt secretion rate was not
      affected. This response was reduced but not blocked by pretreatment with
      phentolamine, an alpha-adrenergic blocker, at a dose that prevented the blood
      pressure response. Infusion of noradrenaline, a mainly alpha-adrenergic agonist,
      into the hepatic artery mimicked the response. Infusion of isoprenaline, a beta
      adrenergic agonist, also reduced the volume outflow of bile from the liver. The
      biliary clearances of mannitol and polyethylene glycol 900, both of which are
      suggested to reflect canalicular events, were reduced by stimulation of the
      splanchnic nerves and infusion of noradrenaline. It is concluded that stimulation
      of the alpha-adrenergic receptors reduces the bile acid-independent bile
      secretion. This reduction in bile flow induced by stimulation of the splanchnic
      nerves and infusion of noradrenaline is elicited mainly at the canalicular level.

PMID- 1980048
TI  - [Fertility after the surgical treatment of cryptorchism].
AB  - The authors carried out a study on the ejaculates of 85 men at the age of 16 to
      38 years, who underwent surgical intervention for treatment of unilateral and
      bilateral cryptorchidism. The patients were divided into two basic groups:
      orchidopexy was made in 66 patients with cryptorchidism and unilateral
      orchidectomy was performed in 19 patients with atrophy of the cryptorchidic
      testis. Surgical treatment of cryptorchidism improved fertile capability in
      15.30% of the patients. The high percentage of 84.70% of the infertile patients
      after surgical treatment of cryptorchidism raises the question for earlier
      surgical treatment of cryptorchidism up to 5 years of age. Orchidectomy is
      indicated in abdominal or highly retained in the inguinal canal testis with very
      short blood vessels. Orchidectomy is also indicated in patients with atrophic
      testes, in whom perspective for fertile capability lacks and presents high risk
      of malignization.

PMID- 1980049
TI  - [H2-receptor antagonists in obstetrical-gynecological anesthesiological practice.
      II. New H2-receptor antagonists].

PMID- 1980050
TI  - Anaesthetic management of a patient with a single ventricle and
      phaeochromocytoma.

PMID- 1980051
TI  - The relationship between bovine major histocompatibility complex class II
      polymorphism and disease studied by use of bull breeding values.
AB  - The predictive value of class II DQ and DYA polymorphisms of the bovine major
      histocompatibility (MHC) complex (BoLA) for the incidence of disease in dairy
      cattle was estimated in a sample of 196 progeny-tested AI bulls of the Swedish
      Red and White breed. The BoLA DQ and DYA types of the bulls were determined by
      analysing restriction fragment length polymorphisms (RFLPs). Breeding values of
      bulls for clinical mastitis, all diseases including clinical mastitis and
      diseases other than clinical mastitis were used as measures of disease resistance
      or susceptibility. The relationship between MHC polymorphism and bull breeding
      values for disease resistance was evaluated statistically by linear regression
      analysis. A significant association between the haplotype DQ1A and susceptibility
      to clinical mastitis was revealed. No other DQ haplotype nor the DYA locus has a
      significant effect on any of the disease traits studied.

PMID- 1980052
TI  - Restriction fragment length polymorphism of bovine lysozyme genes.
AB  - Genetic polymorphism of bovine lysozyme (LYZ) genes was investigated by analysing
      restriction fragment length polymorphism (RFLP). The analysis revealed three RFLP
      loci designated LYZ1, LYZ2 and LYZ2. Each system included two or three allelic
      variants. Evidence for close genetic linkage of the three loci was found. There
      was also a significant linkage disequilibrium among the three loci in a sample of
      about 200 breeding bulls from one breed. No statistically significant association
      was found between LYZ RFLPs and breeding values of bulls for disease or milk
      production traits.

PMID- 1980054
TI  - Myelination and Dysmyelination. Papers presented at a conference. Arlington, Va,
      November 16-18, 1989. Proceedings.

PMID- 1980053
TI  - An AluI polymorphism near the 5' end of the goat epsilon IV globin gene.

PMID- 1980055
TI  - [Drug prescription in myocardial postinfarction: results of the EPPI (etude de
      prescription postinfarctus). A French cooperative study].
AB  - An enquiry into the prescribing behaviour in patients discharged from hospital
      after myocardial infarction was performed in 36 hospital departments in France
      and included 528 patients. Each patient was prescribed an average of 3.6 drugs.
      The most commonly prescribed drug was Aspirin (63.3%) followed by the calcium
      antagonists (61.7%) long acting nitrate derivatives (49.5%) and betablockers
      (41.5%). These results suggest that many post-infarction prescriptions disregard
      recently acquired scientific knowledge.

PMID- 1980056
TI  - Identification of pancreatic glucagon cells in the cartilaginous fish
      Scyliorhinus canicula by ultrastructural immunocytochemistry.
AB  - The ultrastructural localization of glucagon in the presence of Scyliorhinus
      canicula was investigated. We used a post-embedding immunoelectron microscopy
      method on pancreatic samples fixed in glutaraldehyde and osmicated before
      embedding. Contrasting with uranyl acetate and lead citrate was also performed
      after immunolabelling, but best results were obtained with uranyl acetate only.
      Glucagon-like immunoreactivity was located in round granules (300-600 nm)
      surrounded by a limiting membrane. The matrix varied in electron density and
      exhibited a dense core surrounded by a less dense mantle. The granules were seen
      in two different cell types, which differed in the electron density of their
      cytoplasm. Glucagon-immunoreactive cells were the largest pancreatic cells types
      and were often localized near somatostatin-containing cells.

PMID- 1980057
TI  - The endocrine pancreas of Triturus cristatus: an immunocytochemical study.
AB  - The endocrine pancreas of Triturus cristatus carnifex was studied with the aid of
      immunocytochemical methods, showing cells immunoreactive to anti-insulin serum (B
      cells), a small population of cells immunoreactive to anti-glucagon serum only (A
      cells), rare cells positive to anti-PP serum only (PP or F cells), and a larger
      population of cells immunoreactive both to anti-glucagon and to anti-PP sera. B
      cells lied in the core of the islet, while the A/PP cells were located at the
      periphery, forming digitations extending into the exocrine parenchyma. D cells
      were present in small number in the islet while they were more numerous scattered
      in the exocrine parenchyma. A/PP cells as well as D cells showed one or two long
      cytoplasmic extensions often in contact with blood vessels.

PMID- 1980058
TI  - Neutron beam design, development, and performance for neutron capture therapy.
      Proceedings of an international symposium. March 29-31, 1989, Cambridge,
      Massachusetts.

PMID- 1980059
TI  - [Pasteurella multocida (type D and A) and atrophic rhinitis of swine-
      hemagglutination, fimbriae and adhesion in vitro in the nasal mucosa of swine
      fetuses].
AB  - 79 strains of P. multocida were investigated, mostly isolated from porcine nasal
      cavities, and a mannose-resistant hemagglutination with guinea pig and human
      group 0, but not with porcine erythrocytes was found. Fimbriae as adhesins were
      demonstrated only on 2 strains. A correlation between capsular type,
      hemagglutination, fimbriation and toxigenicity on the examined P. multocida
      strains was not observed. Three strains were investigated for the adherence to
      the nasal mucosa of neonatal pigs; aggregates shown by scanning electron
      microscopy indicate colonization; a correlation of adherence with surface
      proteins and slime production of P. multocida is discussed.

PMID- 1980060
TI  - Polymorphism of mitochondrial DNA (mtDNA) in cattle and buffaloes.
AB  - Mitochondrial DNA (mtDNA) from two breeds of cattle, viz., [Hariana (Bos
      indicus), Holstein (Bos taurus)] and Indian water buffalo (Bubalis bubalus), was
      analyzed using 13 restriction endonucleases which recognized an average of about
      40 six-base sites. Polymorphism among cattle was detected with six of these
      enzymes. The two Holstein differed at six sites, whereas the Hariana breed (Bos
      indicus) did not show any site polymorphism. Surprisingly, the Hariana type
      differed by only one site from one of the Holstein types. The total size of
      buffalo mtDNA was estimated to be 16.4 kb. Polymorphism within the Murrah buffalo
      breed was observed with respect to a Bg/I site. Scarcely any of the restriction
      fragments of buffalo mtDNA matched those of cattle mtDNA.

PMID- 1980061
TI  - Polymorphisms and gross structure of glycophorin genes in common chimpanzees.
AB  - Using human alpha glycophorin cDNA probe and six restriction enzymes, we examined
      the homologues of human glycophorin genes in genomic DNA of 11 unrelated
      chimpanzees. We show that, in contrast to the human, the chimpanzee exhibits an
      unusual array of nonrandomly distributed restriction fragment length
      polymorphisms (RFLP). No clear correlation was found between the RFLP and the V-A
      B-D blood-group phenotypes of the subjects, with one possible exception. However,
      pairs of allelic RFLP occurring at a relatively high frequency were identified.
      In addition, the homology of chimpanzee glycophorin genes to the human genes was
      examined using as probes synthetic oligonucleotides specifying distinct regions
      of human glycophorin genes. We show that the glycophorin gene family in the
      chimpanzee consists of at least three members that are homologous to the human
      alpha, delta, and E genes (glycophorins A, B, and E) and may share a similar
      gross structure and overall organization.

PMID- 1980063
TI  - Changes in the properties of cytosolic acetyl-CoA carboxylase studied in cold
      clamped liver samples from fed, starved and starved-refed rats.
AB  - We have used the cold-clamping technique to study the changes in acetyl-CoA
      carboxylase activity that occur in the cytosolic and mitochondrial fractions of
      the liver of fed, starved and starved-refed rats. No evidence was found for a
      role of the mitochondrial enzyme as a pool from which cytosolic carboxylase could
      be replenished upon refeeding of starved rats. Starvation for 24 h or 48 h
      induced changes in the expressed (assayed at 20 mM-citrate), total (citrate- and
      phosphatase-treated) and citrate-independent activities of cytosolic carboxylase,
      as well as in its Ka for citrate. The expressed/total activity ratio was low even
      in the fed state and was depressed further by starvation. The effects of
      refeeding occurred in two phases: an acute phase (approx. 1 h) in which the
      starvation-induced changes in Ka and expressed/total activity ratio were rapidly
      reversed, and a prolonged slow phase in which the two parameters attained values
      that were lower and higher, respectively, than those in the normal fed state.
      Refeeding also resulted in a gradual increase in citrate-independent activity of
      acetyl-CoA carboxylase. An additional marked increase in this activity occurred
      only in 48 h-starved-refed rats between 24 h and 48 h of refeeding. These
      findings are discussed in terms of the observed time courses of changes in
      lipogenic rates that occur in vivo in starved-refed rats and of the possible
      molecular mechanisms involved.

PMID- 1980065
TI  - Significance of transglutaminase-catalyzed reactions in growth and development of
      filarial parasite, Brugia malayi.
AB  - A novel form of transglutaminase enzyme [EC 2.3.2. 13] was identified in adult
      worms of Brugia malayi. The molecular size of this enzyme was 22-kilodaltons as
      determined by Western blot and immunoprecipitation, using a monoclonal (CUB 7401)
      or polyclonal antibodies against guinea-pig liver tissue transglutaminase. The
      enzyme was present in female worms only; adult males contained no detectable
      levels of the enzyme peptide. Possible involvement of transglutaminase-catalyzed
      reactions in growth and survival of filarial parasites was studied by using
      various enzyme-specific pseudosubstrates. Presence of these inhibitors resulted
      into a significant inhibition of microfilariae production and release by gravid
      female worms in a dose-dependent manner. These results suggest that
      transglutaminase-catalyzed reactions are essential for development of in utero
      growing embryos to mature microfilariae.

PMID- 1980064
TI  - Site-directed mutagenesis of beta-lactamase I. Single and double mutants of Glu
      166 and Lys-73.
AB  - Two single mutants and the corresponding double mutant of beta-lactamase I from
      Bacillus cereus 569/H were constructed and their kinetics investigated. The
      mutants have Lys-73 replaced by arginine (K73R), or Glu-166 replaced by aspartic
      acid (E166D), or both (K73R + E166D). All four rate constants in the acyl-enzyme
      mechanism were determined for the E166D mutant by the methods described by
      Christensen, Martin & Waley [(1990) Biochem. J. 266, 853-861]. Both the rate
      constants for acylation and deacylation for the hydrolysis of benzylpenicillin
      were decreased about 2000-fold in this mutant. In the K73R mutant, and in the
      double mutant, the rate constants for acylation were decreased about 100-fold and
      10,000-fold respectively. All three mutants also had lowered values for the rate
      constants for the formation and dissociation of the non-covalent enzyme-substrate
      complex. The specificities of the mutants did not differ greatly from those of
      wild-type beta-lactamase, but the hydrolysis of cephalosporin C by the K73R
      mutant gave 'burst' kinetics.

PMID- 1980066
TI  - Staurosporine, a potent inhibitor of C-kinase, enhances drug accumulation in
      multidrug-resistant cells.
AB  - Staurosporine, a potent inhibitor of C-kinase, enhances accumulation of
      vincristine (VCR) in multidrug-resistant cells. We investigated this enhancement
      by two methods: (I) ATP-dependent VCR binding system; (II) azidopine
      photolabeling system. The ATP-dependent VCR binding to the resistant cell
      membrane was inhibited more efficiently by staurosporine than by verapamil.
      Staurosporine also inhibited the azidopine photolabeling of P-glycoprotein. These
      results indicate that staurosporine, an inhibitor of C-kinase, might directly
      bind to P-glycoprotein as well as antitumor agents and Ca2+ channel blockers.
      These findings also indicate that C-kinase might be involved in the function of P
      glycoprotein.

PMID- 1980062
TI  - Molecular mechanisms of drug resistance.

PMID- 1980067
TI  - Multiple mRNAs of monkey tyrosine hydroxylase.
AB  - The multiplicity of tyrosine hydroxylase (TH) mRNA was examined in two species of
      primate, Macaca irus and Macaca fuscata, one species of insectivore, Sunkus
      murinus and one species of rodent, rat. To investigate the TH multiplicity, total
      RNAs from various species of animals were reverse transcribed and 5' portion of
      TH cDNAs were amplified by polymerase chain reaction. The resulted DNA fragments
      were analyzed by agarose gel electrophoresis. Two types of TH mRNA corresponding
      to type 1 and type 2 were detected in adrenal gland and brain of both species of
      primate. In contrast, only a single form of TH mRNA was detected in Sunkus
      murinus and rat.

PMID- 1980068
TI  - Strategic location of calcium channels at transmitter release sites of frog
      neuromuscular synapses.
AB  - The localization of Ca2+ channels relative to the position of transmitter release
      sites was investigated at the frog neuromuscular junction (NMJ). Ca2+ channels
      were labeled with fluorescently tagged omega-conotoxin GVIA, an irreversible Ca2+
      channel ligand, and observed with a confocal laser scanning microscope. The Ca2+
      channel labeling almost perfectly matched that of acetylcholine receptors which
      were labeled with fluorescent alpha-bung-arotoxin. This indicates that groups of
      Ca2+ channels are localized exclusively at the active zones of the frog NMJ.
      Cross sections of NMJs showed that Ca2+ channels are clustered on the presynaptic
      membrane adjacent to the postsynaptic membrane.

PMID- 1980069
TI  - Induction and expression of long- and short-term neurosecretory potentiation in a
      neural cell line.
AB  - In a neural cell line, the secretion of excitatory amino acids in response to a
      depolarizing stimulus is potentiated by the addition of serotonin. The duration
      of this potentiation is dependent on the strength of the stimulus. Persistent
      secretory potentiation induced by a strong stimulus requires the activation of
      both serotonin and NMDA receptors. Inhibiting the NMDA receptor during serotonin
      presentation prevented the induction of potentiation. The temporal characteristic
      of the potentiation is correlated with the elevation of cAMP levels. Serotonin
      exposure while inhibiting NMDA receptors results in a transient elevation of cAMP
      levels, whereas coactivation with NMDA and serotonin results in a persistent
      elevation of cAMP. Thus, it is possible to obtain potentiation of secretion in a
      single cell either transiently or persistently. The timing of potentiated
      responses in this system is of the same magnitude as that in similar systems used
      as models for short-term and long-term memory.

PMID- 1980070
TI  - Characterization of a target-derived neuronal cholinergic differentiation factor.
AB  - The sympathetic innervation of rat sweat glands undergoes a target-induced switch
      from a noradrenergic to a cholinergic and peptidergic phenotype during
      development. Treatment of cultured sympathetic neurons with sweat gland extracts
      mimics many of the changes seen in vivo. Extracts induce choline
      acetyltransferase activity and vasoactive intestinal peptide expression in the
      neurons in a dose-dependent fashion while reducing catecholaminergic properties
      and neuropeptide Y. The cholinergic differentiation activity appears in
      developing glands of postnatal day 5 rats and is maintained in adult glands. It
      is a heat-labile, trypsin-sensitive, acidic protein that does not bind to heparin
      agarose. Immunoprecipitation experiments with an antiserum directed against an N
      terminal peptide of a cholinergic differentiation factor (CDF/LIF) from heart
      cells suggest that the sweat gland differentiation factor is not CDF/LIF. The
      sweat gland activity is a likely candidate for mediating the target-directed
      change in sympathetic neurotransmitter function observed in vivo.

PMID- 1980071
TI  - [Localization of RFLP probe Fr. 3-42 at 16p 13 band by in situ hybridization].
AB  - Recombinant plasmid clone Fr. 3-42(HGM9 no. D16S21) containing a human single
      copy DNA segment of 1.9kb was hybridized to human chromosome preparations. Twenty
      eight percent of hybridized metaphases exhibited silver grains at the terminal
      region of short arm of chromosome 16 (16p13). Close linkage between this probe
      and the human alpha 1 hemoglobin gene was demonstrated in another study.

PMID- 1980072
TI  - [Changes in serum levels of specific and total IgE in patients with allergic
      rhinopathy treated with H2 antagonists].
AB  - A study has been made of the effects of H2 antagonists in patients with perennial
      allergic rhinitis with sensitivity towards a single allergen: parietaria. During
      two years of observation. The patients underwent three cycles of treatment "a la
      demande". In 70% of the cases an improvement was observed in the symptomatology
      and a decrease in total serum IgE, while specific IgE remained unvaried.
      Subsequent treatments showed results overlapping the first, with further
      improvements.

PMID- 1980073
TI  - Clinical significance of receptor regulation in cardiovascular and respiratory
      diseases. Satellite symposium to the IV World Conference on Clinical Pharmacology
      and Therapeutics. Essen, FRG, July 28-30, 1989. Proceedings.

PMID- 1980074
TI  - Differential regulation of human cardiac beta-adrenergic and muscarinic receptors
      by chronic beta-adrenoceptor antagonist treatment.
AB  - In patients undergoing coronary artery bypass grafting chronic beta 1
      adrenoceptor antagonist treatment increased right atrial beta 1-adrenoceptor
      number, did not affect beta 2-adrenoceptor number and decreased muscarinic M2
      receptor number. Concomitantly, the M2-receptor-mediated negative inotropic
      effect of carbachol was reduced, while the beta 1-adrenoceptor-mediated positive
      inotropic effect of noradrenaline was not altered. The beta 2- adrenoceptor
      mediated positive inotropic effect of procaterol, however, was markedly enhanced.
      We conclude that chronic beta 1-adrenoceptor antagonist treatment increases beta
      1-adrenoceptor number, sensitizes beta 2-adrenoceptor function and desensitizes
      M2-receptor function in the human heart.

PMID- 1980075
TI  - Phorbol-12,13-dibutyrate antagonizes the alpha 1-adrenoceptor-mediated positive
      inotropic effect in the rabbit ventricular myocardium.
AB  - The phorbol ester phorbol-12,13-dibutyrate (PDBu) elicited a slight but
      significant positive inotropic effect (PIE) (10-100 nM) in the presence of a beta
      adrenoceptor antagonist (+/-)-bupranolol (300 nM). PDBu (10-1000 nM) inhibited
      the alpha 1-adrenoceptor mediated PIE in a concentration-dependent manner, while
      beta-adrenoceptor-mediated PIE was not decreased by PDBu up to 300 nM. Thus, PDBu
      exerted a differential effect on alpha- and beta-adrenoceptor-mediated PIE, and
      was much more effective than 12-O-tetradecanoylphorbol-13-acetate (TPA) in
      antagonizing the alpha-adrenoceptor-mediated PIE. These findings imply that (1)
      certain subcellular process of myocardial alpha-adrenoceptor stimulation may be
      specifically antagonized by an activation of protein kinase C induced by PDBu or
      TPA; (2) there may be species difference in the response to activation of protein
      kinase C, which results in differential modulation of myocardial alpha 1
      adrenoceptor-mediated regulation of contractility among different mammalian
      species.

PMID- 1980076
TI  - Different desensitization mechanisms of two alpha 1-adrenoceptor subtypes in the
      contraction of rabbit aorta.
AB  - Using alpha 1-adrenoceptor selective antagonists chlorethylclonidine (CEC) and
      WB4101, both functional and radioligand binding studies showed that rabbit aorta
      contains at least two pharmacologically distinct alpha 1-adrenoceptor subtypes of
      approximately 10% alpha 1a and 90% alpha 1b receptors, and that each receptor
      subtype has a distinct role in the alpha 1-adrenoceptor-mediated vasoconstrictive
      response through different biochemical mechanisms for increasing intracellular
      Ca2+; alpha 1a receptors cause tonic response predominantly dependent on the
      influx of extracellular Ca2+, while alpha 1b receptors stimulate
      phosphoinositides (PI) hydrolysis/intracellular Ca2+ mobilization and cause
      phasic response mainly independent of extracellular Ca2+. Incubation of rabbit
      aorta with 10 microM noradrenaline (NA) for 2 h resulted in a reduction in the
      phasic response and PI hydrolysis to NA with no change in the tonic response.
      Similar to the NA incubation, the protein kinase C stimulator PMA (1 microM)
      selectively attenuated alpha 1b-receptor mediated PI hydrolysis and phasic
      contraction but had little effect on alpha 1a-receptor-mediated tonic response.
      The protein kinase C inhibitor H-7 (10 microM) blocked these inhibitory effects
      of PMA. Treatment with H-7 (10 microM) prevented the NA-induced alpha 1b receptor
      desensitization in inositol monophosphate (IP) formation and phasic response. The
      results suggest that activation of C kinase may be involved in the development of
      selective desensitization of alpha 1b receptors by a short-time in vitro
      incubation of NA.

PMID- 1980077
TI  - Cyclic AMP antagonizes mitogen-induced accumulation of inositol phosphates in
      human peripheral mononuclear leucocytes in vitro.
AB  - The effect of intracellular increases of cyclic adenosine monophosphate (cAMP) on
      the accumulation of inositol phosphates (IPs) in response to various mitogens in
      vitro in human peripheral mononuclear leucocytes (MNL) was investigated. The beta
      adrenoceptor agonists inhibited mitogen-induced IPs-accumulation by about 30-50%
      with a rank order of potency isoprenaline greater than adrenaline much greater
      than noradrenaline. This rank order corresponded with the order of potency of the
      beta-adrenoceptor agonists to generate cAMP. The beta-adrenoceptor agonist
      induced inhibition of IPs-accumulation in response to mitogen could be completely
      prevented by the beta 2-adrenoceptor selective antagonist ICI 118,551, but not by
      the beta 1-adrenoceptor selective antagonist CGP 20712A. Furthermore, the
      isoprenaline-induced inhibition of IPs-accumulation in response to mitogen could
      be enhanced by the phosphodiesterase inhibitor IBMX. We conclude that cAMP
      antagonizes mitogen-induced IPs-accumulation in human peripheral MNL in vitro.

PMID- 1980078
TI  - Effect of calcium and beta-adrenoceptor antagonists on beta-adrenoceptor density
      and Gs alpha expression in human atria.
AB  - In 21 patients undergoing open heart surgery the effects of the beta-adrenoceptor
      antagonists propranolol and sotalol and the calcium antagonist nifedipine (alone
      or in combination) on right atrial beta-adrenoceptor density and G protein
      expression were studied. The non-selective beta-adrenoceptor antagonists
      increased both right atrial beta 1- and beta 2-adrenoceptor density; this
      increase was not affected by nifedipine. There was no correlation between beta
      adrenoceptor density and expression of the G protein subunit Gs alpha suggesting
      independent regulation of the gene expression for G proteins and their coupled
      receptors.

PMID- 1980079
TI  - Independent sensitization of beta-adrenoceptors and adenylate cyclase in acute
      myocardial ischaemia.
AB  - 1. Acute myocardial ischaemia provokes sensitization of the adenylate cyclase
      system. This sensitization could be differentiated in a receptor-linked and an
      enzyme-linked sensitization. The increase in the number of beta-adrenoceptors in
      the plasma membranes was observed already after 15 min of global ischaemia (50 +/
      2 to 67 +/- 6 fmol mg-1 protein) and persisted after 50 min of ischaemia. The
      maximally isoprenaline-stimulated adenylate cyclase activity rose from 66 +/- 7
      to 100 +/- 10 pmol cAMP min-1 mg-1 protein after 15 min of global ischaemia
      indicating the receptor-mediated sensitization of the beta-adrenergic system.
      However, after 50 min of ischaemia the isoprenaline-stimulated adenylate cyclase
      was reduced by about 50% despite the continuous increase of beta-adrenoceptors in
      the plasma membranes. 2. Additionally direct stimulation of the adenylate cyclase
      by forskolin revealed an increased enzyme activity after 15 min of global
      ischaemia (300 +/- 20 vs 378 +/- 25 pmol cAMP min-1 mg-1). Prolonged periods of
      ischaemia, however, caused a decline of the total adenylate cyclase activity (232
      +/- 24 pmol cAMP min-1 mg-1 protein). This demonstrates an enzyme-specific
      sensitization of the adenylate cyclase, which in contrast to the rise in beta
      adrenoceptors is only transient. This enzyme-specific sensitization or the late
      inactivation of the enzyme occur independently of receptor activation and cannot
      be prevented by beta-adrenoceptor blockade (10(-6) M alprenolol) prior to the
      ischaemic insult.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1980081
TI  - The effects of ras gene expression on glucocorticoid receptors in mouse
      fibroblasts.
AB  - Analysis of induction of glutamine synthetase activity by dexamethasone showed a
      2-fold increase in NIH3T3 but no change in NIH3T3 ras (EJ-ras) cells. The
      observed increase could be abolished by the antagonist RU486. The lack of
      response in ras transformed cells might reflect oncoprotein effects on the
      glucocorticoid receptor (GR). Several GR parameters were studied in order to
      clarify this point. Total GR level was the same for both cells; cytoplasmic
      receptor level however, was 3 times lower in NIH3T3 ras than in NIH3T3 cells.
      Hormone-receptor binding affinity, specificity, thermostability, sedimentation
      coefficient, molecular weight as well as the cytoplasmic GR transformation ratio
      were similar for the two cell lines. On the other hand, the fraction of the total
      receptor pool involved with the recycling process was approximately 20% lower in
      NIH3T3 ras than in NIH3T3 cells. After 24 h of dexamethasone treatment, no GR
      down regulation was observed in NIH3T3 ras cells, whereas normal NIH3T3 cells
      exhibited a decrease of GR binding capacity around 80%. Further studies are
      necessary to define the mechanisms underlying the association between
      glucocorticoid insensitivity, and modifications in the GR nuclear/cytoplasmic
      ratio, in the recycling GR fraction and in the down-regulation process observed
      in ras transformed cells.

PMID- 1980080
TI  - The role of DA1- and DA2-receptors in the control of blood pressure.
AB  - 1. Endogenous dopamine, acting through specific receptors on blood vessels, renal
      tubules and adrenal cortical cells, may play a role in the development and
      maintenance of the hypertensive state. 2. In hypertensive patients, activation of
      the DA1-receptor with intravenous fenoldopam produces a rapid and sustained
      reduction in blood pressure, in contrast to the tachyphylaxis seen in some rat
      models. 3. Activation of the DA2-receptor also represents a viable
      antihypertensive approach, based on the chronic efficacy of hydergine. However,
      none of the recently developed selective DA2-receptor agonists has been shown to
      reduce blood pressure in man. 4. Since animal experiments suggest qualitatively
      different antihypertensive profiles for quinpirole and SK&F 101468, both presumed
      to be selective agonists at the DA2-receptor, it may be possible to design new
      DA2-receptor agonists more effective as antihypertensive drugs. 5. Dopamine
      receptors at different sites, even if of the same subtype, can be differentially
      regulated; this may be a consequence of activation of multiple second messenger
      systems by receptor occupation.

PMID- 1980082
TI  - Working toward clinical nursing excellence.
AB  - The professional nursing literature offers limited explication of the meaning of
      clinical nursing excellence, thus few strategies to facilitate and maintain
      excellence in practice. The purpose of this paper is to describe a workshop that
      was designed to give definition and practice directions for the concept of
      "clinical nursing excellence". Workshop participants were the nursing leaders of
      a large Canadian university teaching hospital. The program structure was
      presented by a working committee from within that group and the content was
      provided by those in attendance. The objectives for this two-day workshop were:
      1. To identify characteristics of clinical nursing excellence within the
      organization. 2. To describe programs, activities, and functions (current and
      future) that are consistent with clinical nursing excellence. 3. To identify
      those factors inhibiting and supporting clinical nursing excellence within the
      institution. 4. To promote networking and communication between nursing leaders
      within the Nursing Department. 5. To promote Departmental/Directorate development
      of a plan for further enhancement of clinical nursing excellence. This
      cooperative workshop was deemed a worthwhile endeavour for all participants.
      Nurse administrators may find the process and or products of this workshop useful
      for identifying departmental strategies to enhance nursing practice.

PMID- 1980083
TI  - Mapping of reactive sulfhydryls in avian liver 3-hydroxy-3-methylglutaryl
      coenzyme A synthase.
AB  - Avian liver mitochondrial 3-hydroxy-3-methylglutaryl coenzyme A synthase contains
      seven sulfhydryls per 53 kDa subunit. Peptides that harbor these sulfhydryls can
      be mapped by reverse-phase HPLC separation of tryptic digests of denatured 14C
      carboxymethylated enzyme. Native enzyme is inactivated by a variety of reagents
      that target cysteine residues. Of particular interest is the enzyme's sensitivity
      to reagents (e.g., CdCl2, copper phenanthroline) that target vicinal thiols. The
      identity of the cysteines which are modified by these reagents can be determined
      by peptide mapping after denaturation. 14C-carboxymethylation and trypsin
      digestion of the sample. While the extent of reaction of any particular cysteinyl
      sulfhydryl depends on the identity of the reagent employed, three of the
      protein's seven cysteinyl sulfhydryls are frequently modified upon inactivation
      of the enzyme. The peptides which contain these reactive sulfhydryls have been
      isolated and their sequences have been determined by Edman degradation
      techniques. Comparison of these sequences with the deduced primary structure of
      the rodent cytosolic enzyme (Gil et al. (1986) J. Biol. Chem. 261, 3710)
      indicates strong homologies. These homologies allow assignment of the reactive
      residues as Cys-129, Cys-224 and Cys-268. The sensitivity of these residues to
      reagents that target vicinal thiols, coupled with the fact that cys-129 is the
      residue involved in formation of the acyl-S-enzyme intermediate (Vollmer et al.
      (1988) Biochemistry 27, 4288), suggests that these three residues may be closely
      juxtaposed within the enzyme's catalytic domain.

PMID- 1980084
TI  - Analysis of the kinetic mechanism of halophilic NADP-dependent glutamate
      dehydrogenase.
AB  - The amination of 2-oxoglutarate catalyzed by NADP-specific glutamate
      dehydrogenase (EC 1.4.1.4, L-glutamate:NADP+ oxidoreductase (deaminating)) from
      Halobacterium halobium has been analyzed by initial rate, graphical analysis, and
      product and competitive inhibition studies. Initial rate and graphical analysis
      reveal that a B term (representing 2-oxoglutarate) is not statistically necessary
      for an initial rate equation. However, the absence of a B term does not
      distinguish between ordered and random binding of NADPH and ammonia. The patterns
      of product inhibition by NADP+ and L-glutamate, and competitive inhibition by
      hydroxylamine and succinate permit deduction of the kinetic mechanism as ordered,
      with NADPH, 2-oxoglutarate and ammonia added in that order, and L-glutamate
      release preceding NADP+ release.

PMID- 1980085
TI  - Technical considerations in aortocoronary bypass grafting.
AB  - Since the inception of aortocoronary bypass surgery, many technical advances have
      been rapidly achieved. Early experience was limited to reversed saphenous vein
      grafting of single vessel coronary artery disease. Multiple grafts to several
      vessels soon became commonplace and sequential grafting techniques were
      developed. Expanded use of the internal mammary artery resulted after analysis of
      superior patency rates achieved with this conduit. Use of alternative conduits
      such as upper extremity veins, allogenic veins, synthetic graft material
      (polytetrafluorethylene), radial artery, splenic artery, and gastroepiploic
      artery have been explored. Apart from the gastroepiploic vessel, none of these
      alternative conduits have been suitable. A grat deal of effort has been directed
      at the mechanisms of saphenous vein occlusion including technical considerations,
      early thrombosis, intimal hyperplasia and graft atherosclerosis. Platelet
      inhibition and lipid reduction have shown promise in improving patency rates.
      Further work in these areas should lead to even better results.

PMID- 1980086
TI  - [Modifying effects of neurotropin on post-radiation disorders of neuromediator
      processes in the autonomic function regulation centers].
AB  - In experiments on Wistar rats, it was shown that 6 months after exposure to
      ionizing radiation (X-radiation 0.5 Gy and intraperitoneal 131I 6.5 mCu/kg) the
      hypothyroid state was accompanied by changes in inhibitory and excitatory
      mediation that are characteristic of chronic radiation stress in cerebral
      structures responsible for regulation of autonomic and animal functions and a
      relative deficiency of the hypothalamopituitary-adrenocortical axis. Application
      of therapeutic doses of neurotropin 3 months after radiation levelled the pattern
      of chronic radiation stress and diencephalic disorders that underlie disturbances
      of some systemic functions of the organism.

PMID- 1980087
TI  - [Increase of the number of bone marrow T-suppressor cells under inhibition of
      immunogenesis during changes of the activity of the neuromediator system].
AB  - Increase of serotoninergic system activity and blockade of dopaminergic system
      activity led to the change of T- and B-lymphocyte distribution in immunocompetent
      organs of non-immunized animals. Increase of suppressor cel number with Lyt2.2
      phenotype was found in bone marrow of C57Bl/6 mice under activation of
      serotoninergic system (blockade of serotonin reuptake by sertraline) as well as
      under blockade of dopaminergic system by administration of dopamine autoreceptor
      agonist--3-PPP. Role of bone marrow in neuro-immunomodulation is discussed.

PMID- 1980088
TI  - [Long-term follow-up study on surgical treatment of cryptorchism in children].
AB  - This article reports 1010 cases of cryptorchism managed by surgical treatment
      during the recent 30 years. The age range of the patients was from 4 months to 14
      years. This series includes 342 left side, 456 right side and 212 bilateral
      lesions. Orchiopexy was performed on 1145 testes with three different forms of
      fixation excluding 33 cases of absent testis and 44 cases of testicular agenesis.
      Four hundred and fifty-five cases (527 testes) were available for follow-up
      study. Four hundred and seventeen testes (79.1%) descended into the scrotum,
      while 237 testes (45%) manifested atrophy. The results showed that orchiopexy
      into sub-dartos pouch and surgical treatment during 1 to 2 years of age can give
      the best results. In this article is discussed the age for surgical treatment,
      procedure of testicular fixation, surgical treatment of cryptorchism with
      impalpable testes, prevention of testicular atrophy etc.

PMID- 1980089
TI  - Severe secretory diarrhea with elevated gastrin-releasing peptide controlled by
      somatostatin analogue: a case report.
AB  - Gastrin-releasing peptide immunoreactivity has been seen in functioning endocrine
      tumours which are recognized as a major cause of secretory diarrhea. The authors
      describe a case of a 52-year-old woman who had secretory diarrhea (5 L/d) with
      markedly elevated gastrin-releasing peptide levels associated with islet cell
      hyperplasia. No tumour could be identified. The diarrhea was controlled by
      somatostatin analogue.

PMID- 1980090
TI  - Dermatobia hominis myiasis masquerading as an infected sebaceous cyst.
AB  - In an apparently routine case, what appeared to be infected sebaceous cysts of
      the scalp turned out to harbour botfly larvae imported from a tropical country.
      Although the parasite Dermatobia hominis is not indigenous to the United States,
      cutaneous myiasis caused by the fly is fairly common in Central and South
      America, and several cases have been reported in people returning or emigrating
      from these regions. The authors therefore suggest that infection resulting from
      D. hominis invasion be considered in persons who present with furuncular lesions
      and give a history of travel to endemic areas.

PMID- 1980091
TI  - Tardive dyskinesia and the law.

PMID- 1980092
TI  - Tardive dyskinesia: legal and preventive aspects.
AB  - Tardive dyskinesia is a complication associated with long term neuroleptic drug
      treatment that can be the object of litigation. Such litigation has occurred
      recently in the United States, where awards of considerable value have been
      granted to plaintiffs. Circumstances that can lead to TD litigation are presented
      as well as guidelines for the prescription of neuroleptics, the prevention of
      litigation and of the syndrome itself. Five lawsuits associated with TD serve as
      a backdrop for the discussion.

PMID- 1980093
TI  - Microtubule-associated proteins from Antarctic fishes.
AB  - Microtubules and presumptive microtubule-associated proteins (MAPs) were isolated
      from the brain tissues of four Antarctic fishes (Notothenia gibberifrons, N.
      coriiceps neglecta, Chaenocephalus aceratus, and a Chionodraco sp.) by means of a
      taxol-dependent, microtubule-affinity procedure (cf. Vallee: Journal of Cell
      Biology 92:435-442, 1982). MAPs from these fishes were similar to each other in
      electrophoretic pattern. Prominent in each preparation were proteins in the
      molecular weight ranges 410,000-430,000, 220,000-280,000, 140,000-155,000, 85,000
      95,000, 40,000-45,000, and 32,000-34,000. The surfaces of MAP-rich microtubules
      were decorated by numerous filamentous projections. Exposure to elevated ionic
      strength released the MAPs from the microtubules and also removed the filamentous
      projections. Addition of fish MAPs to subcritical concentrations of fish tubulins
      at 0-5 degrees C induced the assembly of microtubules. Both the rate and the
      extent of this assembly increased with increasing concentrations of the MAPs.
      Sedimentation revealed that approximately six proteins, with apparent molecular
      weights between 60,000 and 300,000, became incorporated into the microtubule
      polymer. Bovine MAPs promoted microtubule formation by fish tubulin at 2-5
      degrees C, and proteins corresponding to MAPs 1 and 2 co-sedimented with the
      polymer. MAPs from C. aceratus also enhanced the polymerization of bovine tubulin
      at 33 degrees C, but the microtubules depolymerized at 0 degrees C. We conclude
      that MAPs are part of the microtubules of Antarctic fishes, that these proteins
      promote microtubule assembly in much the same way as mammalian MAPs, and that
      they do not possess special capacities to promote microtubule assembly at low
      temperatures or to prevent cold-induced microtubule depolymerization.

PMID- 1980094
TI  - Ca/Ba/Sr-induced conformational changes of ciliary axonemes.
AB  - Macrocilia of the ctenophore Beroe undergo Ca/Ba/Sr-dependent activation of
      ciliary beating and microtubule sliding disintegration [Tamm, J. Comp. Physiol.
      A163:23-31, 1988a; Tamm, Cell Motil. Cytoskeleton 11:126-138, 1988b; Tamm, Cell
      Motil. Cytoskeleton 12:104-112, 1989; Tamm and Tamm, Proc. Natl. Acad. Sci.
      U.S.A. 86:6987-6991, 1989]. Here we report that detergent-extracted macrocilia
      show an ATP-independent conformational change in response to high concentrations
      of Ca, Ba, or Sr ions. When applied locally by iontophoresis, these ions induce a
      rapid planar curvature of the distal end of the macrociliary shaft, followed by a
      slower relaxation to the rest position. Tip curling occurs in a direction
      opposite to the physiological Ca/Ba/Sr response. When applied uniformly in the
      bath, a threshold concentration of 10(-1) M Sr is required to induce curling of
      the tip, and the distal ends remain curved. Calmodulin antagonists do not inhibit
      the tip curling response. Previous workers found that Ca induces changes in the
      helical shape of isolated doublet microtubules [Miki-Noumura and Kamiya, Exp.
      Cell Res. 97:451-453, 1976; Miki-Noumura and Kamiya, J. Cell Biol. 81:355-360,
      1979; Takasaki and Miki-Noumura, J. Mol. Biol. 158:317-324, 1982] and sperm
      axonemes [Okuno and Brokaw, Cell Motil. 1:349-362, 1981] and suggested that
      conformational changes in microtubules may play a role in Ca regulation of
      ciliary motility. We propose that the Ca/Ba/Sr-induced curling of the
      macrociliary tip is due to similar helical changes of doublet microtubules, some
      of which in macrocilia are prevented from sliding by permanent connections
      (compartmenting lamellae) between adjacent axonemes within the shaft. Although
      the tip curling response does not appear to be directly relevant to the
      physiological Ca response of macrocilia, it provides a novel system for
      investigating Ca-induced conformational changes of microtubules independent of
      dynein-powered active sliding.

PMID- 1980095
TI  - [3 new cases of internal male pseudohermaphroditism].
AB  - The authors report 3 new cases of Male Internal Pseudohermaphrodism. It is a
      scarce entity. The discovery is fortuous during the cure of hernia or
      cryptorchidism. The family history has nothing particular. The main problem of
      this syndrome is its treatment. Our attitude consisted in conserving the
      mullerian derivatives and treating the hernia or the cryptorchidism. Hysterectomy
      is not justified for the following reasons; no case of cancerisation of the
      mullerian derivatives has not yet been reported. The vasa deferens and uterus are
      in intimate relationship; the dissection is therefore dangerous. We did not
      perform systematic castration in order to protect fertility. The removal of the
      testis is performed only when the gland is intraabdominal and undescendable
      considering the major risk of cancerisation.

PMID- 1980096
TI  - X-linked myopia: Bornholm eye disease. Linkage to DNA markers on the distal part
      of Xq.
AB  - Linkage analysis in a family with X-linked myopia gave a positive LOD score (z =
      4.8 at theta = 0) for linkage to F8C. These results suggest a provisional
      assignment for the locus of this syndrome to the distal part of the X chromosome
      at Xq28. Based on the clinical and genetic evidence, a redefinition of this
      clinical syndrome, named Bornholm Eye Disease (BED), was made to include
      amblyopia, myopia, and deuteranopia. Facultative signs were optic nerve
      hypoplasia, reduced electroretinographic flicker function, and non-specific
      retinal pigment abnormalities.

PMID- 1980097
TI  - Gene-gene interaction between the low density lipoprotein receptor and
      apolipoprotein E loci affects lipid levels.
AB  - A restriction fragment length polymorphism (RFLP) at the low density lipoprotein
      receptor (LDLR) locus, detectable with the restriction enzyme PvuII has been
      studied in a second series of Norwegian subjects, believed to be representative
      of the general population. The results confirm the association of normal alleles
      at the LDLR locus with differences in age- and sex-corrected total and LDL
      cholesterol. A gene identified as one of the alleles in this RFLP appears to
      eliminate the effect of the apolipoprotein E4 (apoE4) gene on cholesterol (or its
      allele must be present for the apoE4 effect on lipid level to manifest itself).
      The findings in this series substantiate previous indications that normal alleles
      are of importance in the control of LDLR activity and that normal LDLR alleles
      contribute to the population variation in cholesterol. Finally, they confirm that
      an interaction between LDLR and apoE genes contributes to the population
      variation in total and LDL cholesterol.

PMID- 1980098
TI  - Different pathohistological presentations of acute renal involvement in Hantaan
      virus infection: report of two cases.
AB  - We present two patients with Hantaan virus infection, admitted to the Department
      of Nephrology, Skopje, at the same time, with the same clinical presentation
      (chills, fever, abdominal pain, hemorrhages, nausea, headache, proteinuria,
      hematuria, oliguria, acute renal failure) but with different pathohistological
      findings and different disease courses. In the first case diffuse proliferative
      glomerulonephritis was found, with a complete recovery of renal function after a
      month, with a mild proteinuria and erythruria during the second and the third
      month. In the second case, glomeruli were normal in general, with slight
      mesangial proliferation found in two out of twenty, but interstitial edema,
      lymphocyte infiltrations and tubular changes were noted. Complete recovery was
      not noted after 3 months of follow-up. The patient is now without hemodialysis
      treatment, with polyuria, in the stable phase of chronic renal failure which is
      not improving.

PMID- 1980099
TI  - Adult metachromatic leukodystrophy without deficiency of arylsulphatase.
AB  - An adult case of metachromatic leukodystrophy, proved by characteristic findings
      of the brain and superficial sural nerve biopsies, but with absence of deficiency
      of arylsulphatase A activity in the leucocytes, was reported. The long course of
      thirty years, the absence of deficiency of arylsulphatase A activity, the
      discrepancy between the normal conduction velocity of the peripheral nerves and
      the typical pathological findings of the superficial sural nerve under the light
      and electron microscopes and the significance of the diffuse hypodense areas and
      high intensity signals of the cerebral white matter on CT and MRI respectively,
      were discussed.

PMID- 1980100
TI  - Histamine modulates dopamine-induced contraction in canine tracheal smooth
      muscle.
AB  - Since exogenous dopamine is commonly used to treat patients of cardiovascular
      failure, its action on the histamine-sensitized airways is critical for asthmatic
      subjects. In this study, in vitro canine airway smooth muscle preparation were
      employed to investigate whether histamine-treatment affects the responsiveness of
      airway smooth muscle to dopamine. The results of our study demonstrate that, at
      dopamine tachyphylaxis of canine tracheal smooth muscle, histamine treatment
      could recover the contraction to dopamine. In the muscle strips sensitized with
      histamine, the dopamine-induced contraction was decreased by the antagonist to
      alpha 2-adrenoceptors and increased by the antagonist to beta 1-adrenoceptors. It
      is concluded that histamine can modulate the dopamine response of canine tracheal
      smooth muscle by sensitizing, transiently, multiple receptors in the muscle which
      are responsible for the contractile response to dopamine.

PMID- 1980101
TI  - [Ultimate tensile strength of plasma- and laser-welded cast titanium (Titaniumer,
      Ohara)].
AB  - The ultimate tensile strength (UTS) of titanium castings (Titaniumer, Ohara) as
      cast and after plasma-welding, laser-welding and soldering was investigated
      according to DIN 13912. The UTS of titanium as cast was 567 (+/- 36) MPa. After
      plasmawelding UTS decreased by 69% on the average, after laser-welding by 20%,
      after soldering with Ag65Cu20Pd15 (1060 degrees C) by 46% and after soldering
      with Ag72Cu20Ti8 (980 degrees C) by 63%. The highest tensile strength was
      observed in laser-welded titanium under the conditions described.

PMID- 1980102
TI  - The Third Japan-US Conference on Biostatistics in the Study of Human Cancer.
      November 11-13, 1988, Hiroshima, Japan. Proceedings.

PMID- 1980103
TI  - Symposium on structural properties for determining mechanisms of toxic action.
      October 18-20, 1988, Duluth, Minnesota. Proceedings.

PMID- 1980105
TI  - The functional and structural roles of residues Gln114 and Glu117 in elongation
      factor Tu.
AB  - The effects of substituting residues Gln114 by Glu and Glu117 by Gln, both
      situated in the vicinity of the guanine-nucleotide-binding pocket, were
      investigated in the isolated N-terminal domain (G domain) of elongation factor Tu
      with respect to the binding of the substrate GDP/GTP, GTPase activity and
      stability. The major change in the interaction with the guanine nucleotides is a
      lower affinity for GTP and a reduced GTPase activity when Gln114 is substituted
      by Glu. This mutation also abolishes most of the selective effects on the GTPase
      activity induced by the different monovalent cations. Substitution of Glu117 by
      Gln does not affect the interaction with the guanine nucleotides or the GTPase
      activity of the G domain in an essential way, but it reduces the stability
      towards denaturation of the G-domain.GDP complex. Our results therefore suggest,
      that Gln114 is involved in keeping a functional conformation of the guanine
      nucleotide-binding pocket, whereas Glu117 participates in the regulation of the
      overall conformation of the G domain. Neither of these two residues appears to
      play a role in the actual GTPase mechanism.

PMID- 1980106
TI  - Uptake of glutamate in Corynebacterium glutamicum. 1. Kinetic properties and
      regulation by internal pH and potassium.
AB  - The active uptake system for glutamate in Corynebacterium glutamicum is inducible
      by growth on glutamate as sole energy and carbon source and is also susceptible
      to catabolite repression by glucose. The basic level of uptake activity is low in
      glucose-grown cells (1.5 nmol.mg dry mass-1.min-1), it is intermediate when
      acetate is the carbon source (3.8 nmol.mg dry mass-1.min-1) and becomes fully
      induced by glutamate (15 nmol.mg dry mass-1.min-1). In all cases the uptake has,
      except for different Vmax values, identical kinetic and energetic properties, and
      is characterized by a low apparent Km value of 0.5-1.3 microM and by high
      substrate specificity. The transported substrate species is the deprotonated form
      which can also be concluded from the extremely high pH optimum of transport above
      pH 9. Glutamate uptake in cells grown in media with low K+ concentration is not
      influenced by external Na+ but is drastically stimulated by addition of K+.
      Stimulation by K+ could be separated into two different mechanisms. (a) Addition
      of K+ increases the internal pH, thereby stimulating glutamate uptake which is
      regulated by the internal pH in C. glutamicum. The apparent pK of the internal
      'pH switch' is 6.6; below this value, uptake of glutamate is inhibited. (b)
      Internal K+ also directly promotes glutamate uptake. Effective uptake of
      glutamate can be observed only when the cytosolic K+ concentration exceeds a
      threshold value of about 200 mM. Stimulation of glutamate uptake by external K+
      is not due to functional coupling of K+ and glutamate transport but reveals the
      necessity to replenish the internal K+ pool.

PMID- 1980104
TI  - Overview of herbicide mechanisms of action.
AB  - Commercial herbicides exhibit many different mechanisms of action. Several
      enzymes involved in biosynthesis of amino acids are sites of action for
      herbicides. A large number of different herbicide classes inhibit photosynthesis
      by binding to the quinone-binding protein, D-1, to prevent photosynthetic
      electron transfer. Several different types of herbicides apparently cause
      accumulation of photodynamic porphyrins by inhibiting protoporphyrinogen oxidase.
      Bipyridyliums and heteropentalenes cause the production of superoxide radicals by
      energy diversion from photosystem I of photosynthesis. Lipid synthesis is the
      site of action of a broad array of herbicides used in controlling monocot weeds.
      Herbicides of several classes apparently act by inhibiting mitosis through direct
      interaction with tubulin. Several other molecular sites of herbicide action are
      known. Despite a growing body of knowledge, the exact molecular sites of action
      of many herbicides are unknown. Some herbicides are known to have more than one
      site of action. Virtually all knowledge of herbicide structure-activity
      relationships is semiempirical. In addition to site of action structure-activity
      relationships, herbicide structure and chemical properties also strongly
      influence absorption, translocation, bioactivation, and environmental stability.
      Considering how little is known about all the potential sites of herbicide
      action, it is unlikely that during the next decade more than a relatively small
      number of site-specific herbicide structure-activity relationships will be
      developed.

PMID- 1980107
TI  - Uptake of glutamate in Corynebacterium glutamicum. 2. Evidence for a primary
      active transport system.
AB  - The inducible glutamate uptake system in Corynebacterium glutamicum (Kramer, R.,
      Lambert, C., Hoischen, C. & Ebbighausen, H., preceding paper in this journal) was
      characterized with respect to its mechanism and energy coupling. All possible
      secondary active uptake mechanisms can be excluded. Glutamate transport is not
      coupled to the translocation of H+, Na+ or K+ ions. Although changes in membrane
      potential and uptake activity cannot completely be separated, no correlation
      between these two parameters is observed. The uptake of glutamate resembles a
      primary active, ATP-dependent transport mechanism in several respects. (a) The
      substrate affinity is very high (1.3 microM). (b) Accumulation of glutamate
      reaches values of greater than 2.10(5), at least as high as those reported for
      binding-protein-dependent systems in Gram-negative bacteria. (c) The uptake is
      unidirectional. Even after complete deenergization, the accumulation ratio was
      not significantly reduced. (d) The rate of glutamate uptake is directly
      correlated to the cytosolic ATP content and also to the ATP/ADP ratio. This is
      shown by varying internal ATP by different procedures applying inhibitors (NaCN,
      dicyclohexyl carbodiimide), uncouplers (carbonyl m-chlorophenylhydrazone),
      ionophores (valinomycin), and even by shifting the cells to anaerobiosis. Uptake
      is not promoted by cytosolic ATP levels below 1.5 mM, the maximum uptake rate is
      reached at 4-5 mM ATP.

PMID- 1980109
TI  - In vitro analysis of age-related changes in the developmental potential of bone
      marrow thymocyte progenitors.
AB  - Mechanisms underlying the age-related decrease in the developmental capacity of
      thymocyte progenitors from the bone marrow (BM) were analyzed, focussing on
      interaction of these cells with the thymic microenvironment. We employed the
      experimental model in which mixtures of young and old mouse BM cells, congenic
      for the Thy-1 marker, were seeded onto fetal thymus (FT) explains depleted of
      self lymphocytes and the levels of Thy-1+ cells developing from each of the two
      donor types were measured. When cells from young and old BM donors were seeded
      simultaneously, in saturating quantities, a higher level of T cells developed
      from the young donors. To find out whether there were originally more thymocyte
      progenitors in the young BM, we carried out the competitive colonization under
      limiting dilution conditions and found that the advantage of the young had
      diminished under these conditions, thus suggesting that the age-related changes
      could not be related solely to quantitative differences. We then incubated the FT
      sequentially with old donor cells for 24 h, followed by young for an additional
      48 h and found that the advantage of the young progenitors was eliminated. We
      thus established that the initial stage of colonization of the FT was important
      in determining the outcome of the subsequent development. The kinetics of
      simultaneous competition within the FT, however, revealed that the advantage of
      the young BM-derived cells became significant only from day 7 in organ culture,
      thus suggesting that sequential divisions of these cells were at a higher level
      than those of the old. Recolonization of FT explants by young or old BM-derived
      thymocytes obtained from the first colonization of the FT stroma showed a
      reduced, but still significant advantage for the young BM-derived cells over the
      old. Thus, we concluded that the old BM thymocyte progenitors manifested a
      qualitative disadvantage which became apparent during competitive colonization of
      the FT.

PMID- 1980108
TI  - Immunization of susceptible hosts with a soluble antigen fraction from Leishmania
      major leads to aggravation of murine leishmaniasis mediated by CD4+ T cells.
AB  - This study was performed in order to define Leishmania major antigens that
      function as disease-modulating immunogens in susceptible BALB/c mice. A soluble
      leishmanial antigen preparation (S-SLA) derived from highly infective stationary
      phase L. major parasites was fractionated by preparative gel electrophoresis. In
      vitro, the low molecular mass fraction (less than 31 kDa) of S-SLA fraction D (FR
      D) was found to be a potent stimulator of L. major-specific Th1 and Th2 helper
      cell clones. In vivo, immunization with FR D induced a Th2-biased immune response
      in BALB/c mice as determined by the numbers of splenic CD4+ cells secreting
      interleukin 4 and interferon-gamma according to limiting dilution analyses. In
      addition, FR D caused significant disease exacerbation in parasite-infected
      susceptible mice as assessed by the local lesion development and the numbers of
      parasites in lymph nodes and spleen. This effect was observed after local
      subcutaneous application of FR D as well as after systemic immunization
      (intrasplenic or intraperitoneal). Transfer experiments revealed, that the
      disease-aggravating effect of FR D was mediated by CD4+ T cells. From these
      results it is concluded that leishmanial protein preparations exist that not only
      fail to induce protective anitparasitic immunity, but can mediate disease
      exacerbation, independently of the primary application site of the immunogen. The
      existence of such structures may serve the parasite as a means to evade the
      host's immune attack and may also have implications for the development of
      vaccines.

PMID- 1980110
TI  - A monoclonal antibody directed against the human intercellular adhesion molecule
      (ICAM-1) modulates the release of tumor necrosis factor-alpha, interferon-gamma
      and interleukin 1.
AB  - ICAM-1 is a cell surface glycoprotein which is one of the ligands for the
      leukocyte function-associated antigen (LFA-1). It is involved in leukocyte
      adhesion to endothelial cells as well as in immune functions requiring cell-cell
      contact. The quantitative expression of ICAM-1 in various cell types can be
      either induced or enhanced by treatment with cytokines, such as interferon-gamma
      (IFN-gamma), tumor necrosis factor (TNF)-alpha or interleukin 1 (IL 1), a
      phenomenon which results in the augmentation of binding to LFA-1-positive cells.
      In contrast, treatment with anti-ICAM-1 antibodies blocks this binding. A
      monoclonal antibody (mAb), termed 7F7, which recognizes an epitope on ICAM-1, was
      used to investigate the role of ICAM-1 in cytokine production by T lymphocytes
      and monocytes. Production of TNF-alpha. IFN-gamma and IL1 was significantly
      inhibited (p less than 0.01) by the incubation of mAb 7F7 with phytohemagglutinin
      activated blood mononuclear cells (MNC) or isolated E rosette-positive T
      lymphocytes. The maximal level of inhibition was reached with 1 microgram/ml of
      purified antibody. A similar inhibition was obtained using saturating
      concentrations of 400 microliters/ml of mAb 7F7 hybridoma supernatant
      corresponding to an inhibitory activity of 1 microgram of purified mAb. In
      contrast, granulocyte/macrophage-colony-stimulating factor release showed a
      heterogeneous response over five experiments with an increase found in three
      experiments and a decrease in two experiments. Addition of increasing
      concentrations of supernatant or purified mAb to unstimulated MNC or T lymphocyte
      cultures had no effect on cytokine release. The observed inhibition of the
      production of TNF-alpha. IFN-gamma and IL 1 by antibody-mediated blockade of the
      ICAM-1 structure probably represents a negative circuit that serves to tune the
      activation of leukocytes and to avoid an overproduction of cytokines.

PMID- 1980111
TI  - Evidence that in X-linked immunodeficiency with hyperimmunoglobulinemia M the
      intrinsic immunoglobulin heavy chain class switch mechanism is intact.
AB  - X-linked immunodeficiency with hyperimmunoglobulinemia M (XHM) reflects an
      impairment of the immunoglobulin (Ig) heavy (H) chain class switch of B
      lymphocytes from IgM to IgG and IgA. XHM is recessive; female carriers manifest
      normal IgG and IgA production. Due to random X chromosome inactivation in all
      somatic cells of females, about half of the lymphocytes of XHM carriers are not
      able to express an intact XHM gene. An intrinsic defect of the Ig H chain class
      switch mechanism in XHM B lymphocytes would thus lead to a skewed X chromosome
      inactivation pattern in the IgG- and IgA-expressing B lymphocytes of female
      carriers. IgM-, IgG- and IgA-expressing B lymphoblastoid cells (BLC) were
      established by Epstein-Barr virus transformation of peripheral blood mononuclear
      cells of two female XHM carriers. In an analysis of differential methylation of
      the polymorphic DXS255 loci, random X chromosome inactivation patterns were found
      in populations of T lymphocytes, in IgM-expressing B lymphocytes and in IgG- or
      IgA-expressing B lymphocytes. The heterogeneity of Ig H chain rearrangements and
      the Ig light chain usage in the IgA- or IgG-expressing BLC clones that had
      inactivated the X chromosome which carries the intact XHM gene and in BLC clones
      with the homologous X chromosome inactivated were similar. The results indicated
      that the intrinsic Ig H chain class switch mechanism in XHM B lymphocytes is
      fully intact. We conclude that the XHM gene encodes a class switch inducer that
      is transferred to B lymphocytes.

PMID- 1980112
TI  - The induction of skin graft tolerance in major histocompatibility complex
      mismatched or primed recipients: primed T cells can be tolerized in the periphery
      with anti-CD4 and anti-CD8 antibodies.
AB  - Mice given short courses of anti-CD4 and anti-CD8 monoclonal antibodies became
      tolerant of allogeneic skin grafted at the same time. Tolerance could be obtained
      without T cell depletion across multiple minor antigen mismatches, both in naive
      and primed animals, demonstrating that peripheral T cells could be tolerized,
      even if they had been previously activated. Where donor and recipient were
      incompatible across the whole major histocompatibility complex, specific
      tolerance could be achieved by using a combination of depleting followed by non
      depleting antibodies, where each alone was unsuccessful. Although mice clearly
      tolerated their original skin grafts, we observed in some strain combinations
      that a second fresh, but genotypically identical graft, was slowly rejected. Such
      mice also possessed T cells which could proliferate to donor-type stimulator
      cells in vitro. Whatever the mechanisms, we have demonstrated that operational
      transplantation tolerance can be achieved with simple, non-toxic antibody
      therapy. The introduction of comparable tolerance-inducing regimens in clinical
      organ transplantation could obviate the need for long-term immunosuppression and
      its unfortunate side effects.

PMID- 1980113
TI  - A three-dimensional model system to study the interactions between human
      leukocytes and endothelial cells.
AB  - Leukocyte adhesion to endothelial cells and migration into the subendothelial
      matrix was studied with a three-dimensional model system, consisting of human
      endothelial cells cultured on a loose collagen matrix. We developed a new method
      to separate the endothelial cell monolayer and adhering leukocytes, from the
      subendothelial matrix, allowing simultaneous analysis of leukocyte adhesion and
      transendothelial migration. Monocytes adhered more avidly to untreated
      endothelial cells than did neutrophils (2.5 +/- 0.3 vs. 1.0 +/- 0.2 leukocytes
      per endothelial cell). Only a small fraction (10%-20%) of these leukocytes
      migrated into the subendothelium. Pretreatment of endothelial cells with
      interleukin 1 (IL 1) enhanced adhesion (20%), but not migration of monocytes. In
      contrast, neutrophil adhesion was markedly and in a time-dependent manner
      increased by IL 1 treatment (i.e. 200% after 6 h and 110% after 24 h of IL 1
      treatment). Moreover, IL 1 pretreatment enhanced neutrophil migration twofold.
      Activation of leukocytes with formyl-methionyl-leucyl-phenylalanine (fMLP)
      enhanced both monocyte and neutrophil adhesion, but did not affect leukocyte
      migration. Under all conditions, monocyte adhesion was only partly (30%-40%)
      inhibited by monoclonal antibodies (mAb) against the common beta subunit of the
      leukocyte-cell adhesion molecules (LeuCAM: CD18) and 25%-30% by mAb against the
      alpha subunit of LFA-1 (CD11a). In contrast, mAb against the alpha subunits of
      Mac-1 (CD11b) and p150.95 (CD11c) were hardly effective. fMLP-mediated neutrophil
      adhesion was reduced to below baseline levels by anti-LeuCAM (CD18) mAb, whereas
      the LeuCAM contribution in IL 1-mediated neutrophil adhesion was less pronounced
      and varied in time. IL 1-mediated neutrophil migration, however, was completely
      blocked by anti-LeuCAM mAb. fMLP-mediated neutrophil adhesion was inhibited by
      mAb against the alpha subunits of Mac, while mAb against the alpha subunits of
      LFA-1 and Mac-1 both reduced IL 1-mediated adherence. In summary, we describe a
      novel leukocyte adhesion/migration method and demonstrate that the contribution
      of the LeuCAM complex in leukocyte-endothelium interaction varies depending on
      cell type and stimulus used.

PMID- 1980114
TI  - A unique subset of normal murine CD4+ T cells lacking Thy-1 is expanded in a
      murine retrovirus-induced immunodeficiency syndrome, MAIDS.
AB  - Some strains of mice inoculated with LP-BM5 murine leukemia virus (MuLV) develop
      a syndrome, termed mouse acquired immunodeficiency syndrome (MAIDS),
      characterized by progressive lymphoproliferation and profound immunodeficiency.
      LP-BM5 MuLV is a virus mixture that contains ecotropic (eco) and mink cell focus
      induced MuLV and a defective genome that is the proximal cause of disease. Flow
      cytometry analyses of spleen and lymph nodes from susceptible C57BL/6 mice
      infected with this virus mixture revealed the presence in spleen and peripheral
      lymph nodes of a previously unrecognized subset of CD4+CD3+ T cells that are Thy
      1-. The frequency of these cells increased with progression of disease,
      eventually comprising between 30% and 50% of all CD4+ cells. Infection of A/J
      mice, a strain which is genetically resistant to development of MAIDS, did not
      induce an increase of this T cell population, indicating that infection with the
      virus mixture was insufficient to induce its proliferation. A central role for
      the defective virus in this process was suggested by the finding that C57BL/6
      mice infected with LP-BM5 eco alone did not have increased frequencies of Thy-1
      CD4+ cells in spleen. Studies of spleen and peripheral lymph node cells from
      normal mice demonstrated the presence of Thy-1-CD4+ cells at frequencies of 1%
      2%. Studies using two anti-T cell monoclonal antibodies, SM6C10 and SM3G11, that
      define four CD4+ subsets showed that Thy-1-CD4+ T cells from normal and infected
      mice were present only in the 6C10- subsets.

PMID- 1980115
TI  - Conservation of engrailed-like homeobox sequences during vertebrate evolution.
AB  - The Drosophila melanogaster developmental gene engrailed (en) is a member of a
      distinct subfamily of homeobox genes with a wide phylogenetic distribution. Here
      we report the use of reduced stringency polymerase chain reaction (PCR) to
      amplify and clone 8 genes related to en from 5 vertebrate species, including
      representatives of the most ancient vertebrate lineages. Nucleotide and deduced
      amino acid sequence comparisons between mouse, toad, zebrafish, lamprey and
      hagfish genes reveal extensive evolutionary conservation, and suggests that 2 en
      like genes have been retained in most vertebrate lineages.

PMID- 1980116
TI  - Delayed skin reaction caused by a coelenterate.
AB  - We report a delayed skin reaction, histologically characterized by liquefaction
      degeneration of the basal layer, which was observed in a 30-year-old man
      returning from Guadeloupe. It was most likely due to contact with a marine
      animal.

PMID- 1980117
TI  - The sheep growth hormone receptor: molecular cloning and ontogeny of mRNA
      expression in the liver.
AB  - Two overlapping cDNA clones encoding the sheep growth hormone (GH) receptor were
      isolated from a sheep liver cDNA library. The translated amino acid sequence
      predicts a polypeptide precursor of 634 amino acids with a calculated molecular
      weight of 70,799. The mature GH receptor comprises an extracellular domain of 242
      amino acids, a hydrophobic transmembrane region of 24 amino acids, and a
      cytoplasmic domain of 350 amino acids. The nucleotide and translated amino acid
      sequences display extensive similarity with sequences established for GH
      receptors from a number of other mammalian species. A prominent transcript of 4.5
      kb and a minor transcript of 1.9 kb are detected following Northern blot
      hybridization of poly(A)+ RNA isolated from sheep liver. The onset of GH receptor
      mRNA expression in the liver is developmentally regulated: GH receptor
      transcripts are first detected by Northern blot hybridization in liver taken from
      a term (145 days of gestation) fetus and reach maximum levels within one week
      following birth. Ribonuclease protection assays reveal heterogeneity within the
      5' untranslated region of GH receptor mRNA transcripts detected in liver and a
      number of other tissues. At least one transcript appears to be expressed in a
      liver-specific fashion, supporting a role for alternative RNA splicing in the
      tissue-specific regulation of sheep GH receptor expression.

PMID- 1980118
TI  - A new Drosophila homeo box gene is expressed in mesodermal precursor cells of
      distinct muscles during embryogenesis.
AB  - Several Drosophila homeo box genes have been shown to control cell fates in
      specific positions or cell groups of the embryo. Because the mechanisms involved
      in the pattern formation of complex internal organs, such as the musculature and
      the nervous system, are still largely unknown, we sought to identify and analyze
      new homeo box genes specifically expressed in these tissues. Here, the molecular
      analysis and expression pattern of one such gene, containing both a homeo box and
      a PRD repeat, is described. This gene, designated S59, is expressed in a small
      number of segmentally repeated mesodermal cells approximately 2 hr
      postgastrulation. Gradually, four groups of S59-expressing mesodermal cells
      appear in each abdominal hemisegment, each one giving rise to a particular
      somatic muscle after fusion with surrounding myoblasts. Thus, individual
      precursors for particular muscles, which we call "founder cells," are specified
      relatively early during mesodermal development. The expression of a particular
      homeo box gene in these cells suggests that distinct programs of gene expression
      are active in subsets of mesodermal cells after germ band elongation, resulting
      in a specification of their developmental fates. In addition to the mesoderm, S59
      is expressed in a subset of neuronal cells of the CNS and their precursors and
      also in cells of a small region of the midgut.

PMID- 1980119
TI  - A multisubunit factor, CstF, is required for polyadenylation of mammalian pre
      mRNAs.
AB  - We have purified and characterized a factor required for accurate polyadenylation
      of mammalian pre-mRNAs in vitro. This factor, called cleavage-stimulation factor
      (CstF), is composed of three distinct polypeptide subunits of 77, 64, and 50 kD.
      Using monoclonal antibodies directed against the 64- and 50-kD subunits, we show
      that CstF is required for efficient cleavage of polyadenylation substrates.
      Furthermore, CstF present in unfractionated nuclear extracts interacts with pre
      mRNAs containing the signal sequence AAUAAA, but not AAGAAA, in such a manner
      that the 64-kD subunit can be cross-linked to the RNA by UV light. This
      polypeptide is thus identical to the previously described 64-kD nuclear protein
      that binds to AAUAAA-containing RNAs. Finally, indirect immunofluorescence of
      fixed cells indicates that CstF is distributed diffusely throughout the nucleus
      in a granular pattern distinct from the "speckled" pattern displayed by factors
      involved in pre-mRNA splicing, but similar to that of heterogeneous nuclear
      ribonucleoproteins. A model is presented in which CstF binds specifically to
      nascent RNA polymerase II transcripts and, by interacting with other factors,
      results in a rapid initiation of 3'-end processing of pre-mRNAs.

PMID- 1980120
TI  - Interactions between lymphocytes and cells of the blood-retina barrier:
      mechanisms of T lymphocyte adhesion to human retinal capillary endothelial cells
      and retinal pigment epithelial cells in vitro.
AB  - We have studied the adhesion of human CD4+ lymphocytes to cultured human retinal
      vascular endothelial cells (EC) and human retinal pigment epithelial cells (RPE),
      both of which comprise the cellular components of the blood-retina barrier. We
      have observed differences in the lymphocyte-RPE and the lymphocyte-EC
      interactions. Firstly, RPE cells were found to express high levels of the
      adhesion molecule ICAM-1 constitutively, whereas EC expressed ICAM-1 only after
      induction with IFN-gamma. In addition, lymphocyte binding to normal and minimally
      stimulated RPE (5 U/ml, 4 hr) was predominantly ICAM-1 dependent, but after
      maximal stimulation (500 U/ml, 4 days), increased lymphocyte adhesiveness
      included an ICAM-1-independent component, which was apparently not due to
      involvement of MHC class II or CD2 molecules. In contrast, binding of lymphocytes
      to unstimulated EC involved both an ICAM-1-dependent and an ICAM-1-independent
      mechanism, the latter being subject to inhibition by monoclonal antibody to CD2.
      Studies of adhesion at 4 indicated that no binding occurred to normal or
      stimulated RPE, but binding to EC was observed, albeit reduced to 50% of the 37
      binding level, and this implies that the LFA-3/CD2 adhesion pathway may also be
      involved in lymphocyte binding to EC. Overall, the results indicate a functional
      difference between RPE and EC affecting T-cell adhesion, migration and activation
      at the blood-retinal barrier, which must be considered when devising therapies to
      prevent lymphocyte infiltration of the eye.

PMID- 1980122
TI  - [Glucophage Symposium--NIDD today. Helsingor, Denmark, September 7-8, 1990.
      Proceedings].

PMID- 1980121
TI  - Phenotypic characteristics of antigen-bearing cells in the draining lymph nodes
      of contact sensitized mice.
AB  - Following contact sensitization of mice there is a rapid accumulation of
      dendritic cells (DC) within lymph nodes draining the site of exposure. Previous
      studies have revealed that cells bearing high levels of contact allergen can also
      be identified within the low buoyant density fraction of draining lymph node
      cells, and it has been assumed that the majority of these are DC. The purpose of
      the present study was to establish the phenotypic characteristics of the antigen
      bearing cells which appear in lymph nodes within hours of skin painting with
      contact allergens, including the contact sensitizing fluorochromes fluorescein
      isothiocyanate (FITC) and rhodamine B isothiocyanate (RITC). Indirect
      immunofluorescence and two-colour immunofluorescence analyses revealed that
      initially all antigen-bearing cells which arrive in the draining lymph nodes
      express class II MHC antigens and exhibit a dendritic morphology. Phagocytic
      cells, cells reactive with F4/80 and anti-Mac-1 antibodies and lymphoblasts are
      not associated with detectable levels of antigen. In addition, although Thy-1+
      cells co-fractionate with lymph node DC they are not dendritic in nature and are
      not associated with antigen. These data are compatible with the hypothesis that
      following skin sensitization epidermal Langerhans' cells bind antigen and
      transport it to the regional lymph nodes. In addition, it is clear that the
      recently described population of Thy-1+, Ia- dendritic cells within the murine
      epidermis do not perform a similar function.

PMID- 1980123
TI  - Aminopeptidase N is directly sorted to the apical domain in MDCK cells.
AB  - In different epithelial cell types, integral membrane proteins appear to follow
      different sorting pathways to the apical surface. In hepatocytes, several apical
      proteins were shown to be transported there indirectly via the basolateral
      membrane, whereas in MDCK cells a direct sorting pathway from the trans-Golgi
      network to the apical membrane has been demonstrated. However, different proteins
      had been studied in these cells. To compare the sorting of a single protein in
      both systems, we have expressed aminopeptidase N, which already had been shown to
      be sorted indirectly in hepatocytes, in transfected MDCK cells. As expected, it
      was predominantly localized to the apical domain of the plasma membrane. By
      monitoring the appearance of newly synthesized aminopeptidase N at the apical and
      basolateral surface, it was found to be directly sorted to the apical domain in
      MDCK cells, indicating that the sorting pathways are indeed cell type-specific.

PMID- 1980126
TI  - Anti-HIV-1 activity of antiviral compounds, as quantitated by a focal immunoassay
      in CD4+ HeLa cells and a plaque assay in MT-4 cells.
AB  - The inhibitory effects of a series of antiviral compounds on human
      immunodeficiency virus type 1 (HIV-1) were evaluated in a plaque assay (PA) in MT
      4 cells and a focal immunoassay (FIA) in CD4+ HeLa cells. Similar 50% inhibitory
      concentrations (IC50) were obtained for the sulfated polysaccharides when
      measured by PA or FIA: the IC50 values of dextran sulfate and pentosan
      polysulfate were 0.8 microgram/ml and 0.35 microgram/ml, respectively. Also,
      comparable IC50 values (ranging from 1.42 to 2.71 microM) were obtained for
      purine 2',3'-dideoxyribosides (i.e. DDA, DDI and DDG) when evaluated by PA or
      FIA. In contrast, the IC50 values of pyrimidine 2',3'-dideoxyribosides were
      invariably 4- to 10-fold lower when monitored by PA than FIA: the IC50s of AZT,
      D4T and DDC in the PA were 0.015, 0.094 and 0.038 microM, respectively, and in
      the FIA were 0.062 microM, 0.29 microM and 0.46 microM, respectively. The
      differential anti-HIV-1 activities found with AZT, D4T and DDC in the PA and FIA
      systems may at least be related in part to differences in the metabolism of the
      compounds (i.e. phosphorylation by thymidine kinase or 2'-deoxycytidine kinase)
      between MT-4 and CD4+ HeLa cells. The novel anti-HIV-1 compounds tetrahydro
      imidazo[4,5,1-jk][1,4]-benzodiazepin-2(1H)-thione (TIBO) derivatives, R82150 and
      R82913, and the acyclouridine derivative 1-[(2-hydroxyethoxy)methyl]-6
      phenylthiothymine (HEPT) were also more inhibitory to HIV-1 in the PA than FIA
      system. The IC50 values of R82150, R82913 and HEPT, as based on PA, were 0.005,
      0.003 and 0.79 microM, respectively. Their IC50 values, as based on FIA, were
      0.020 microM, 0.015 microM and 3.77 microM, respectively. The TIBO derivatives
      emerged as the most effective HIV-1 inhibitors of the compounds tested whether
      assayed by PA or FIA.

PMID- 1980125
TI  - Oncogene amplification correlates with dense lymphocyte infiltration in human
      breast cancers: a role for hematopoietic growth factor release by tumor cells?
AB  - One hundred six primary breast cancer samples were analysed for c-erbB2, int-2,
      and c-myc gene amplification. Surgically confirmed nodal involvement was observed
      in 42%. Level of gene amplification was studied by Southern and/or slot blot
      techniques. Amplified c-erbB2 gene sequences were present in 21.5% of all
      samples. Int-2 was amplified in 13.1% and c-myc was amplified in 10.3%. In a non
      parametric test (Kruskal-Wallis) a strong negative association was found between
      high levels of c-erbB2 amplification and absence of estrogen receptor (ER) (P =
      .0009) or progesterone receptor (PR) (P = .011) expression. No correlations were
      found between all or high levels of amplification of each oncogene separately or
      combined with T, N, grade, multifocality of tumor, or associated carcinoma in
      situ. There was a trend approaching statistical significance for patients with c
      erbB2 amplifications to have positive lymph nodes at surgery (P = 0.09). A
      somewhat surprising finding however was a very strong association between
      oncogene amplification and dense lymphocyte infiltration of the tumor (P = .05).
      This correlation is even stronger when only high levels of amplification are
      considered, either for each oncogene separately (P = .0048) or in combination (P
      = .0007). We propose that malignant cell cytokine production may help explain
      this observation.

PMID- 1980127
TI  - Prevention of opioid side effects.
AB  - Physician education in cancer pain management is seriously deficient. Many
      problems occur with opioids simply because of therapeutic ignorance. Opioid side
      effects are best prevented by using morphine as the drug of first choice for
      severe pain. Anticipation and prevention of opioid side effects avoids most
      problems. Physicians need to be aware of how to transfer patients from one opioid
      to another or from one route of administration to another. Side effects common in
      clinical practice are constipation, nausea/vomiting, dry mouth, and sedation. The
      importance of the issues of tolerance, dependence, and respiratory depression
      have been exaggerated.

PMID- 1980124
TI  - ICAM-1 (CD54): a counter-receptor for Mac-1 (CD11b/CD18).
AB  - While the leukocyte integrin lymphocyte function-associated antigen (LFA)-1 has
      been demonstrated to bind intercellular adhesion molecule (ICAM)-1, results with
      the related Mac-1 molecule have been controversial. We have used multiple cell
      binding assays, purified Mac-1 and ICAM-1, and cell lines transfected with Mac-1
      and ICAM-1 cDNAs to examine the interaction of ICAM-1 with Mac-1. Stimulated
      human umbilical vein endothelial cells (HUVECs), which express a high surface
      density of ICAM-1, bind to immunoaffinity-purified Mac-1 adsorbed to artificial
      substrates in a manner that is inhibited by mAbs to Mac-1 and ICAM-1. Transfected
      murine L cells or monkey COS cells expressing human ICAM-1 bind to purified Mac-1
      in a specific and dose-dependent manner; the attachment to Mac-1 is more
      temperature sensitive, lower in avidity, and blocked by a different series of
      ICAM-1 mAbs when compared to LFA-1. In a reciprocal assay, COS cells
      cotransfected with the alpha and beta chain cDNAs of Mac-1 or LFA-1 attach to
      immunoaffinity-purified ICAM-1 substrates; this adhesion is blocked by mAbs to
      ICAM-1 and Mac-1 or LFA-1. Two color fluorescence cell conjugate experiments show
      that neutrophils stimulated with fMLP bind to HUVEC stimulated with
      lipopolysaccharide for 24 h in an ICAM-1-, Mac-1-, and LFA-1-dependent fashion.
      Because cellular and purified Mac-1 interact with cellular and purified ICAM-1,
      we conclude that ICAM-1 is a counter receptor for Mac-1 and that this receptor
      pair is responsible, in part, for the adhesion between stimulated neutrophils and
      stimulated endothelial cells.

PMID- 1980128
TI  - Restriction fragment length polymorphisms in isolates of Aspergillus fumigatus
      probed with part of the intergenic spacer region from the ribosomal RNA gene
      complex of Aspergillus nidulans.
AB  - Differences in restriction fragment length polymorphisms (RFLPs) have been
      detected in isolates of Aspergillus fumigatus. Genomic DNA from 11 isolates was
      digested with EcoRI, separated by electrophoresis, Southern blotted and probed
      with DNA from the intergenic spacer or non-transcribed spacer region of the rRNA
      gene complex of Aspergillus nidulans. Three distinct RFLP patterns were detected
      which differed from the control patterns observed with A. nidulans, Aspergillus
      flavus and Aspergillus niger hybridized with the same probe. Furthermore, the
      differences in RFLP patterns in the A. fumigatus isolates were not detected when
      probed with DNA coding for the rRNA complex in Saccharomyces cerevisiae. These
      findings may be of use in the study of the epidemiology and pathogenesis of
      infections caused by A. fumigatus.

PMID- 1980129
TI  - Developing concepts of the synapses.

PMID- 1980130
TI  - Dynorphin A-(1-17) induces alterations in free fatty acids, excitatory amino
      acids, and motor function through an opiate-receptor-mediated mechanism.
AB  - The endogenous opioid dynorphin A-(1-17) (Dyn A) has been implicated as a
      mediator of tissue damage after traumatic spinal cord injury (TSCI) and causes
      hindlimb paralysis when administered intrathecally. Motor impairment following
      intrathecal Dyn A is attenuated by antagonists of excitatory amino acids (EAAs);
      whether opioid receptors mediate such injury has been questioned. TSCI causes
      various biochemical changes associated with secondary tissue damage, including
      alterations in tissue amio acids, phospholipids, and fatty acids. Such changes
      reflect injury severity and correlate with motor dysfunction. The present studies
      examined whether dynorphin administration causes similar biochemical alterations
      and whether effects of Dyn A can be modified by treatment with opioid-receptor
      antagonists. At 24 hr after intrathecal Dyn A, there were significant declines in
      tissue levels of glutamate, aspartate, and glycine. Increases in total free fatty
      acids were found at 2 and 24 hr, reflecting changes in both saturated and
      unsaturated components, which were associated with significant decreases in
      tissue cholesterol and phospholipid phosphorus at the earlier time point. Each of
      these neurochemical changes, as well as corresponding motor deficits, were
      limited by pretreatment with the opioid antagonist nalmefene. In separate
      experiments, both nalmefene and the selective kappa-opioid antagonist nor
      binaltorphimine (nor-BNI) limited dynorphin-induced motor dysfunction; effects of
      nor-BNI were dose related, and those of nalmefene were stereospecific. Therefore,
      behavioral and neurochemical consequences of Dyn A administration are mediated in
      part through opiate receptors, most likely kappa-receptors.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1980131
TI  - The interactions between plasma membrane depolarization and glutamate receptor
      activation in the regulation of cytoplasmic free calcium in cultured cerebellar
      granule cells.
AB  - The complex modulation of cytoplasmic free calcium concentration ([Ca2+]c) in
      primary cultures of cerebellar granule cells in response to glutamate receptor
      agonists has been the subject of several contradictory reports. We here show that
      3 components of the [Ca2+]c response can be distinguished: (1) Ca2+ entry through
      voltage-dependent Ca2+ channels, following KCl- or receptor-evoked
      depolarization, (2) Ca2+ entry through NMDA receptor channels, and (3) liberation
      of internal Ca2+ via a metabolotropic receptor. Depolarization with KCl induced a
      transient [Ca2+]c response (subject to voltage inactivation) decaying to a
      sustained plateau (largely inhibited by nifedipine). The NMDA response was
      potentiated by glycine, totally inhibited by (+)5-methyl-10,11-dihydro-5H
      dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801), and blocked by Mg2+ in a
      voltage-sensitive manner. Polarized cells displayed small responses to
      quisqualate (QA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid
      (AMPA). Depolarization enhanced a transient response to QA, but not to AMPA.
      Trans-1-amino-1,3-cyclopentanedicarboxylic acid (trans-ACPD), a selective agonist
      for the metabolotropic glutamate receptor, caused a transient elevation of
      [Ca2+]c, which was blocked by prior exposure to QA but not AMPA. The prolonged
      [Ca2+]c response to kainate (KA) can be resolved into 2 major components: an
      indirect NMDA receptor-mediated response due to released glutamate and a
      nifedipine-sensitive component consistent with depolarization-mediated entry via
      Ca2+ channels. 6-Cyano-7-nitroquinoxaline-2,3-dione (CNQX), QA at greater than 10
      microM, and AMPA (but not trans-ACPD) reversed the KA response, consistent with
      an inactivation of the KA receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1980132
TI  - Chronic levodopa treatment alters basal and dopamine agonist-stimulated cerebral
      glucose utilization.
AB  - The effect of chronic levodopa administration on the functional activity of the
      basal ganglia and its output regions was evaluated by means of the 2-deoxyglucose
      (2-DG) autoradiographic technique in rats with a unilateral 6-hydroxydopamine
      lesion of the nigrostriatal pathway. The rates of local cerebral glucose
      utilization were studied under basal conditions as well as in response to
      challenge with a selective D1 or D2 dopamine-receptor agonist. Levodopa (100
      mg/kg/d, i.p.) was administered for 19 d either continuously via infusion with an
      osmotic pump or intermittently by twice-daily injections. Following a 3-d
      washout, glucose utilization was found to be decreased by both levodopa regimens
      in the nucleus accumbens; intermittent levodopa also decreased glucose
      utilization in the entopeduncular nucleus, subthalamic nucleus, ventrolateral
      thalamus, ventromedial thalamus, ventroposterolateral thalamus, and lateral
      habenula. In control (lesioned and treated chronically with saline) rats, the D1
      agonist SKF 38393 (5 mg/kg, i.v.) increased 2-DG uptake in the substantia nigra
      pars reticulata and entopeduncular nucleus ipsilateral to the lesion by 84% and
      56%, respectively. Both continuous and intermittent levodopa blunted the SKF
      38393-induced elevation in glucose metabolism in the substantia nigra pars
      reticulata, while intermittent levodopa also attenuated the increase in the
      entopeduncular nucleus. The D2 agonist quinpirole (0.4 mg/kg, i.v.) did not
      increase glucose utilization in any brain region in control animals; following
      intermittent levodopa treatment, however, quinpirole increased 2-DG uptake by 64%
      in the subthalamic nucleus and by 39% in the deep layers of the superior
      colliculus on the ipsilateral side.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1980133
TI  - Different classes of glutamate receptors and GABA mediate distinct modulations of
      a neuronal oscillator, the medullary pacemaker of a gymnotiform electric fish.
AB  - Gymnotiform electric fish generate distinct communicatory signals by modulating
      the rate of their electric organ discharges (EODs). Each EOD is triggered by a
      command pulse from the medullary pacemaker nucleus (PN), which contains pacemaker
      cells and relay cells. The firing rate of this nucleus is modulated by inputs
      from the diencephalic prepacemaker nucleus (PPN). The NMDA receptor blocker APV
      and the kainate/quisqualate receptor blocker CNQX, administered to the PN,
      suppress different types of modulations, indicating that different classes of
      glutamate receptors mediate the generation of different modulations. A comparison
      of the 2 genera, Hypopomus and Eigenmannia, reveals that sustained modulations,
      such as smooth rises in the rate of pacemaker cell firing and the selective
      silencing of the relay cells (only observed in Hypopomus), are mediated by NMDA
      receptors, whereas the brief and rapid acceleration, called "chirp" or "decrement
      burst," is mediated by kainate/quisqualate receptors. Application of the GABA
      blocker bicuculline reveals that the 2 genera differ in the mechanism by which
      they slow the firing rate of their pacemaker. Whereas Hypopomus uses GABAergic
      inhibition to slow down and ultimately silence its pacemaker cells, Eigenmannia
      reduces tonic, APV-sensitive excitation originating from its PPN and lacks
      GABAergic inhibition in the PN.

PMID- 1980135
TI  - Expression of multiple neurotransmitter receptors by sympathetic preganglionic
      neurons in vitro.
AB  - Neurons in the CNS generally receive inputs form multiple afferent sources. These
      afferent systems seldom all use the same neurotransmitter, so most central
      neurons are required to express multiple neurotransmitter receptors. This work
      addresses the issue of how multiple neurotransmitter receptors are regulated on
      the surface of individual neurons. We made whole-cell voltage-clamp recordings
      from identified chick sympathetic preganglionic neurons (SPNs) in dissociated
      cell cultures. The neurons were derived from stage 30-31 (7 d) chick embryos and
      were studied within the first week in vitro. We found that by 1 week in vitro,
      most SPNs responded to the application of GABA, glycine, and glutamate. The
      responses of SPNs to the amino acid neurotransmitters were similar to the
      responses of other CNS neurons to these 3 substances. SPNs became sensitive to
      these substances at different times in culture. At 1 d in vitro, most cells
      already responded to GABA, and about half of the cells also responded to glycine
      and kainate. In contrast, responses to NMDA and quisqualate were usually not seen
      until day 3-4 in vitro. Although there was a general trend for the amplitude of
      the responses of SPNs to each of the neurotransmitters to increase with time in
      vitro, there was an immense amount of cell-to-cell variability. By measuring the
      amplitudes of the responses of a series of SPNs to all 3 transmitters, we were
      able to test whether a common regulatory mechanism governed the level of
      responsiveness of SPNs to all 3 amino acid transmitters. We found no correlation
      between cells in the amplitudes of their responses to the 3 transmitters. Both
      the differences in time course of appearance of responsiveness and the lack of
      correlation in the amplitude of responses suggest that the multiple receptors on
      the surface of SPNs in vitro are independently regulated.

PMID- 1980134
TI  - Dual effect of glycine on NMDA-induced neurotoxicity in rat cortical cultures.
AB  - To examine the roles of glycine in neurotoxicity caused by NMDA, primary rat
      cortical cultures were exposed to 100-300 microM NMDA plus glycine (0-3000
      microM) or other glycine analogs in a simple saline solution, and toxicity was
      assessed by the amount of lactate dehydrogenase (LDH) released from the cultures.
      NMDA-induced neurotoxicity was abolished by 100 microM D-2-amino-5
      phosphonovaleric acid (D-APV), phencyclidine (IC50, 4.1 microM), and Mg (IC50,
      7.5 mM), or by reducing [Ca]0 to 0.1 mM. NMDA-induced neurotoxicity could also be
      abolished by 7-chlorokynurenic acid (IC50, 8.6 microM), suggesting the presence
      of residual glycine in the culture medium (confirmed by high-performance liquid
      chromatography measurement). Moreover, in the presence of 30 microM 7
      chlorokynurenic acid, glycine, D-serine, D-alanine, beta-fluoro-D-alanine, and 1
      aminocyclopropanecarboxylic acid could restore the neurotoxic action of NMDA, and
      their relative potencies and relative efficacies were the same as measured in
      electrophysiological assays in Xenopus oocytes or cultured neurons. The addition
      of greater than 100 microM glycine doubled the excitotoxic effect of NMDA. The
      potency of glycine was low (EC50, 27 microM), and this effect was not due to a
      direct action on the NMDA receptor. The above-mentioned agonists were unable to
      substitute for glycine, even at high concentrations (1 mM). On the other hand,
      beta-alanine, taurine, and GABA (1 mM) did potentiate NMDA neurotoxicity, and
      strychnine (IC50, 550 nM) could greatly reduce neurotoxicity in the presence of 1
      mM glycine plus 300 microM NMDA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1980136
TI  - Patterns of glutamate immunoreactivity in the goldfish retina.
AB  - Postembedding silver-intensified immunogold procedures reveal high levels of
      glutamate immunoreactivity in "vertical" elements of the goldfish retina: (1) Red
      sensitive and green-sensitive cones display strong glutamate immunoreactivity,
      especially in their synaptic terminals, but blue-sensitive cones are poorly
      immunoreactive. (2) All type Mb (on-center) and Ma (off-center) mixed rod-cone
      bipolar cells and all identifiable cone bipolar cells are highly glutamate
      immunoreactive. We find no evidence for bipolar cells that lack glutamate
      immunoreactivity. (3) The majority of the somas in the ganglion cell layer and
      certain large cells of the amacrine cell layer resembling displaced ganglion
      cells are strongly glutamate immunoreactive. (4) Despite their high affinity
      symport of acidic amino acids, the endogenous levels of glutamate in Muller's
      cells are among the lowest in the retina. (5) GABAergic neurons possess
      intermediate levels of glutamate immunoreactivity. Quantitative
      immunocytochemistry coupled with digital image analysis allows estimates of
      intracellular glutamate levels. Photoreceptors and bipolar and ganglion cells
      contain from 1 to 10 mM glutamate. The bipolar and ganglion cell populations
      maintain high intracellular glutamate concentrations, averaging about 5 mM,
      whereas red-sensitive and green-sensitive cones apparently maintain lower levels.
      Importantly, photoreceptor glutamate levels are extremely volatile, and in vitro
      maintenance is required to preserve cone glutamate immunoreactivity in the
      goldfish. GABAergic horizontal and amacrine cells contain about 0.3-0.7 mM
      glutamate, which matches the values predicted from the Km of glutamic acid
      decarboxylase. Muller's cells and non-GABAergic amacrine cells contain less than
      0.1 mM glutamate. Though Muller's cells are known to possess potent glutamate
      symport, they clearly possess equally potent mechanisms for maintaining low
      intracellular glutamate concentrations.

PMID- 1980137
TI  - The osteogenic potential of two composite graft systems using osteogenin.
AB  - The purpose of this study was to determine the quantity of new bone formation in
      critical sized calvaria defects in rats treated with two composite graft systems.
      The systems consisted of either a combination of the bone inductive protein
      (osteogenin) plus type I collagen (Os + C) or the combination of osteogenin with
      coralline hydroxyapatite (Os + HA). Additional treatments consisted of coralline
      hydroxyapatite (HA) or untreated control defects. After 28 days the calvaria were
      recovered and processed for quantitative radiography (radiomorphometry) and
      histomorphometry. Histomorphometric results were based on quantitation of
      regenerated trabecular bone. Results indicated that the Os + C combination
      produced substantially more bone than the Os + HA, HA, or control groups (P less
      than 0.05). Radiomorphometric assessment was based on the detection of
      radiopacity in the calvarial wounds. Due to the radiopaque property of HA, it was
      not possible to accurately quantitate the radiopacity of the regenerating bone
      from HA and host bone. Therefore, conclusions about the efficacy of the
      treatments must be derived from histomorphometric data. Results from histometric
      measurements of healing indicate that the Os + C combination has the greatest
      potential for regenerating calvarial bone defects. The potential for osteogenin
      in regenerating alveolar bone lost due to periodontal disease is suggested by
      these studies.

PMID- 1980138
TI  - Simultaneous reconstruction of both feet with a vascularized latissimus dorsi
      free flap.
AB  - Simultaneous reconstruction of both feet with a single vascularized latissimus
      dorsi free flap is reported. The authors describe the repair of extensive dorsal
      and plantar defects, as well as of heel lesions secondary to osteitis of the
      calcanei. The latissimus dorsi free flap serves well in combining the classic
      cross-leg procedure with microsurgical techniques.

PMID- 1980140
TI  - Circling behavior exhibited by a transgenic insertional mutant.
AB  - We report here of an abnormal circling behavior expressed in the TgX15 transgenic
      mouse line as a result of insertional mutagenesis. Homozygous transgenic mice
      expressed the phenotype while heterozygous transgenics were normal. We also found
      that the dopamine D2 receptor binding sites in the striata of the circling mice
      were significantly elevated by about 31% compared to normal heterozygous
      transgenic mice. Other transgenic lines constructed with the same transgene
      appeared normal suggesting that, in the TgX15 line, a genetic locus significant
      in mammalian motor behavior has been disrupted.

PMID- 1980139
TI  - Decrease in tyrosine hydroxylase, but not aromatic L-amino acid decarboxylase,
      messenger RNA in rat olfactory bulb following neonatal, unilateral odor
      deprivation.
AB  - Unilateral naris cauterization in rats results in occlusion of the affected naris
      and blockade of odorant access to ipsilateral olfactory receptor cells in the
      olfactory epithelium. These receptor cells project exclusively to the olfactory
      bulb (OB) and appear to regulate expression of the dopaminergic phenotype in a
      population of OB juxtaglomerular neurons. Unilateral odor deprivation results in
      a loss of normal stimulatory input to the OB and a marked and specific decrease
      in ipsilateral OB tyrosine hydroxylase (TH) expression. The expression of co
      localized aromatic L-amino acid decarboxylase (AADC) is not similarly affected.
      We have used this procedure in neonatal rats to examine the effect of stimulus
      deprivation on OB TH and AADC mRNA levels. Both Northern blot and in situ
      hybridization analyses revealed a pronounced decrease in ipsilateral as compared
      to contralateral OB TH mRNA levels 40 days after naris closure. In contrast, the
      levels of OB AADC mRNA were unaltered by naris closure. By in situ hybridization
      histochemistry, both TH and AADC mRNAs were localized to OB juxtaglomerular
      neurons. Odor deprivation was associated with an apparent region-specific
      reduction in TH mRNA within the ipsilateral OB glomerular layer. By densitometric
      analysis, the loss of TH-specific message was quantitatively consistent with the
      decrease in TH activity, suggesting that the observed plasticity of OB
      dopaminergic neurons following functional deafferentation can be attributed to a
      selective, transneuronally-mediated down regulation of TH gene transcription.

PMID- 1980141
TI  - Genetic mapping with dispersed repeated sequences in the rice blast fungus:
      mapping the SMO locus.
AB  - The SMO genetic locus in strains of the fungus Magnaporthe grisea that infect
      weeping lovegrass, directs the formation of correct cell shapes in asexual
      spores, infection structures, and asci. We have identified and characterized a
      Smo- strain of M. grisea that infects rice. The smo mutation in this strain
      segregates as a single gene mutation and is allelic to previously identified smo
      alleles. A marked reduction in pathogenicity co-segregates with the Smo-
      phenotype, suggesting that the SMO locus plays a role in rice pathogenicity. A
      family of dispersed repeated DNA sequences, called MGR, have been discovered in
      the nuclear DNA of M. grisea rice pathogens. Genetic crosses between Smo- rice
      pathogens and Smo+ non-rice pathogens were used to follow the segregation of the
      SMO locus and individual MGR sequences. Using DNA blot analysis with cloned MGR
      hybridization probes, we mapped the SMO locus to a chromosomal region flanked by
      two closely linked MGR sequences. We demonstrated that the copy number of MGR
      sequences could be reduced in subsequent crosses to non-rice pathogens of M.
      grisea, and that new MGR sequences did not occur following meiosis indicating
      that these sequences are stable in the genome. We conclude that restriction
      fragment polymorphism mapping with cloned MGR sequences as hybridization probes
      is an effective way to map genes in the rice blast fungus.

PMID- 1980142
TI  - A previously unrecognized glutamine synthetase expressed in Klebsiella pneumoniae
      from the glnT locus of Rhizobium leguminosarum.
AB  - Using glnT DNA of Rhizobium meliloti as a hybridization probe we identified a R.
      leguminosarum biovar phaseoli (R. l. phaseoli) locus (glnT) expressing a
      glutamine synthetase activity in Klebsiella pneumoniae. A 2.2 kb DNA fragment
      from R. l. phaseoli was cloned to give plasmid pMW5a, which shows interspecific
      complementation of a K. pneumoniae glnA mutant. The cloned sequence did not show
      cross-hybridization to glnA or glnII, the genes coding for two glutamine
      synthetase isozymes of Rhizobium spp. While in previous reports on glnT of R.
      meliloti and Agrobacterium tumefaciens no glutamine synthetase activity was
      detected, we do find activity with the glnT locus of R. l. phaseoli. The
      glutamine synthetase (GSIII) activity expressed in a K. pneumoniae glnA strain
      from pMW5a shows a ratio of biosynthetic to transferase activity 10(3)-fold
      higher than that observed for GSI or GSII. GSIII is similar in molecular weight
      and heat stability to GSI.

PMID- 1980143
TI  - Ante mortem cerebral amino acid concentrations indicate selective degeneration of
      glutamate-enriched neurons in Alzheimer's disease.
AB  - There is little information about major constituents of the brain in Alzheimer's
      disease. In the case of amino acids most of the previous data are contradictory.
      These have been interpreted in an anatomic and neurotransmitter as well as a
      metabolic context. To help clarify this, the contents of 14 amino acids and
      ethanolamine were determined in samples of neocortex from diagnostic craniotomies
      of 15 demented patients (10 with Alzheimer's disease) and other neurosurgical
      procedures (57 patients, 18 with intractable depression). A comprehensive survey
      of the effects of possible complicating factors on the concentrations of amino
      acids showed that artefacts were few; this was in contrast to a post mortem
      series of brains (16 with Alzheimer's disease and 16 controls; six regions
      assayed). We have used the ante mortem data to provide the basis for an accurate
      comparison of amino acid values between Alzheimer and control samples. In
      Alzheimer's disease, the mean contents of many amino acids were slightly higher
      (sum of the increases of those significantly affected was 15 nmol/mg protein)
      whereas glutamate content alone was significantly reduced (by 16 nmol/mg
      protein). This was not a feature of depression or a group of patients with other
      dementias. Glutamate content of Alzheimer samples was related to pyramidal neuron
      density in cortical layer III. These alterations were detected relatively early
      during the course of Alzheimer's disease and are considered to be due to loss of
      corticocortical glutamatergic association pathways.

PMID- 1980144
TI  - Differential alpha-1 and alpha-2 adrenergic effects on hypothalamic corticotropin
      releasing factor and plasma adrenocorticotropin.
AB  - There is presently no consensus as to the nature of the catecholaminergic
      influence on the regulation of corticotropin-releasing factor. The potential role
      that the alpha-adrenergic system plays was investigated by measuring hypothalamic
      corticotropin-releasing factor-like immunoreactivity and plasma
      adrenocorticotropin, following manipulation of alpha-1 and alpha-2 adrenergic
      receptor activation. Administration of the alpha-1 agonist methoxamine did not
      significantly alter either plasma adrenocorticotropin or hypothalamic
      corticotropin-releasing factor. Administration of the alpha-2 agonist clonidine
      resulted in a 24-fold increase in plasma adrenocorticotropin and a significant
      decrease in median eminence corticotropin-releasing factor, consistent with its
      release. Corticotropin-releasing factor in the remainder of the hypothalamus was
      not altered. Concurrent administration of clonidine with the selective alpha-2
      antagonist yohimbine prevented the clonidine-induced changes in plasma
      adrenocorticotropin and hypothalamic corticotropin-releasing factor, consistent
      with the clonidine effect being mediated through alpha-2 receptors. Concurrent
      administration of clonidine with methoxamine did not prevent these effects,
      suggesting that the effect of clonidine was not mediated through presynaptic
      inhibition of noradrenergic adrenergic neurotransmission. Inhibition of protein
      synthesis by anisomycin induced changes in corticotropin-releasing factor and
      adrenocorticotropin which were not altered by combined treatment with methoxamine
      or clonidine. These data suggest differential roles for alpha-1 and alpha-2
      systems in the regulation of corticotropin-releasing factor. Results from alpha-2
      adrenergic activation were consistent with stimulation of corticotropin-releasing
      factor release, an effect mediated by a postsynaptic alpha-2 mechanism.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1980145
TI  - A comparison of the effect of calcium channel ligands and GABAB agonists and
      antagonists on transmitter release and somatic calcium channel currents in
      cultured neurons.
AB  - Glutamate release has been examined from cultured cerebellar granule neurons in
      the rat using the technique of prelabelling the releasable pool of glutamate with
      [3H]glutamine. Glutamate release was stimulated in control neurons by 2-min
      incubation with 50 mM K+, or in neurons continuously depolarized in Ca2(+)-free
      50 mM K+ medium, by 2-min incubation with medium containing 5 mM Ca2+. The
      ability of the Ca2(+)-channel agonist (+)-202-791 to increase the stimulated
      release of [3H]glutamate was approximately doubled in the depolarized condition.
      The antagonist enantiomer (-)-202-791 produced a small inhibition of K(+)
      stimulated release, whereas (-)-202-791 completely inhibited Ca2(+)-stimulated
      release from depolarized neurons at concentrations greater than 10 nM. (-)
      Baclofen (100 microM) inhibited transmitter release similarly (25-30%) under the
      two conditions. Calcium-channel currents were recorded from cultured dorsal root
      ganglion neurons under control conditions at a holding potential of -80 mV, or in
      neurons depolarized to -30 mV. (-)-202-791 produced a greater effect at -30 than
      at -80 mV although even at -30 mV the inhibition was slow in onset and
      incomplete. (-)-Baclofen (100 microM) inhibited the amplitude of the calcium
      channel current at both holding potentials by 30-50%, although it did not clearly
      slow activation of the current at the depolarized holding potential. The GABAB
      receptors associated with inhibition of glutamate release and of calcium-channel
      currents were both markedly blocked by phaclofen but not by 2-OH-saclofen. These
      findings suggest that the GABAB receptor associated with inhibitory modulation of
      transmitter release, and that associated with inhibition of calcium-channel
      currents show pharmacological similarities, and are able to exert their action
      even at levels of steady depolarization at which most N-type channels should be
      inactivated.

PMID- 1980146
TI  - Direct cutaneous hyperalgesia induced by adenosine.
AB  - The intradermal injection of adenosine produces a dose-dependent decrease in
      mechanical nociceptive threshold in the hindpaw of the rat that is not attenuated
      by elimination of indirect pathways for the production of hyperalgesia. Adenosine
      induced hyperalgesia is mimicked by the A2-agonists, 5'-(N-ethyl)-carboxamido
      adenosine and 2-phenylaminoadenosine but not by the A1-agonist, N6
      cyclopentyladenosine and antagonized by the adenosine A2-receptor antagonist, PD
      081360-0002 but not by the A1-antagonist, 1,3-dipropyl-8-(2-amino-4
      chlorophenyl)xanthine. The latency to onset of adenosine and 2
      phenylaminoadenosine hyperalgesia is similar to that produced by prostaglandin
      E2, a directly acting hyperalgesic agent but shorter than that produced by
      leukotriene B4, which acts indirectly. 2-Phenylaminoadenosine hyperalgesia is
      prolonged by rolipram, a phosphodiesterase inhibitor. Both 2-phenylaminoadenosine
      and prostaglandin E2 hyperalgesia are antagonized by the A1-agonist N6
      cyclopentyladenosine and the mu-agonist, [D-Ala2, NMe-Phe4, Gly-ol]enkephalin.
      However, 1-acetyl-2-(8-chloro-10,11-dihydrodibenz[b,f]oxazepine-10-ca rbonyl)
      hydrazine, a prostaglandin-receptor antagonist, inhibits prostaglandin E2 (Taiwo
      and Levine, Brain Res. 458, 402-406, 1988) but not 2-phenylamino-adenosine
      hyperalgesia and PD 081360-0002, the adenosine receptor antagonist, inhibits 2
      phenylamino-adenosine but not prostaglandin E2 hyperalgesia. These data suggest
      that adenosine is a directly acting agent that produces hyperalgesia by an action
      at the A2-receptor and that this hyperalgesia is mediated by the cAMP second
      messenger.

PMID- 1980147
TI  - A pharmacological analysis of the neuronal circuitry involved in distension
      evoked enteric excitatory reflex.
AB  - Isolated segments of guinea-pig small intestine were set up in a partitioned bath
      to study the enteric excitatory reflex evoked by distension. The gut was
      distended by a rubber balloon inserted at the aboral end and contractions of the
      circular muscle were recorded at the oral end. The oral and aboral ends of the
      gut were separated by an intermediate compartment of the bath. Inflation of the
      intraluminal balloon with 0.075-0.35 ml water elicited reproducible and
      distension-dependent contraction. This enteric orally directed (ascending)
      excitatory reflex was abolished by tetrodotoxin irrespective of the compartment
      in which it was applied. Hyoscine (0.3 microM) almost abolished the enteric
      excitatory reflex when it was applied to the oral compartment. This indicates
      that the transmission from the final motor neurons to the circular muscle is
      mainly cholinergic, acting via muscarinic receptors. Hyoscine had no effect on
      the enteric excitatory reflex when added to the intermediate compartment. When
      hyoscine was added to the aboral compartment, it decreased the enteric excitatory
      reflex elicited by low distension stimuli to 70% of control and decreased the
      enteric excitatory reflex elicited by higher distension stimuli to 95% of
      control. This indicates that ganglionic transmission involving muscarinic
      receptors at the site of distension in the aboral bath contributes to the enteric
      excitatory reflex. Hexamethonium (100 microm) greatly depressed the enteric
      excitatory reflex when applied to any compartment indicating that nicotinic
      transmission is most important in the afferent, intermediate and efferent
      components of the reflex and that the reflex pathway involves a polysynaptic
      chain of cholinergic interneurons.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1980148
TI  - Korean hemorrhagic fever: environmental health and medical surveillance measures.
AB  - Throughout history, battles, campaigns, and wars have often been decided by
      diseases, rather than bullets and tacticians. During the Korean War, Korean
      hemorrhagic fever (KHF) afflicted several thousand allied soldiers and an unknown
      number of Communist soldiers. This disease, and other members of a closely
      related group, the hemorrhagic fevers with renal syndrome, represent a continuing
      worldwide military and civilian threat. Through inexpensive and flexible
      environmental health measures, and readily available medical surveillance and
      testing, it is now possible to reduce the risk from this disease. In this paper,
      we will outline various environmental health measures developed to reduce the
      risk of contracting KHF and the justification for their use. We will also discuss
      a medical surveillance and testing program designed to get at-risk and
      symptomatic individuals to definitive care quickly in order to reduce overall
      morbidity and mortality.

PMID- 1980149
TI  - Neural substrates of latent inhibition: the switching model.
AB  - Latent inhibition (LI) refers to decrement in conditioning to a stimulus as a
      result of its prior nonreinforced preexposure. It is a robust phenomenon that has
      been demonstrated in a variety of classical and instrumental conditioning
      procedures and in many mammalian species, including humans. The development of LI
      is considered to reflect decreased associability of, or attention to, stimuli
      that predict no significant outcome. The fact that LI is considered to be a
      reflection of attentional processes has become of increasing importance to
      neuroscientists who see LI as a convenient tool for measuring the effects of drug
      treatments and lesions on attention. The present article surveys the data on
      brain systems, which have been studied in regard to their involvement in LI.
      These are reviewed and discussed separately in sections on noradrenergic,
      cholinergic, dopaminergic, serotonergic, and septo-hippocampal manipulations. On
      the basis of these data, it is concluded that the neural substrates of LI include
      the mesolimbic dopaminergic system, the mesolimbic serotonergic system, and the
      hippocampus. It is proposed that the preexposed stimulus loses its capacity to
      affect behavior in conditioning, even though it predicts reinforcement, because
      the hippocampus inhibits the switching mechanism of the nucleus accumbens via the
      subiculum-accumbens pathway. This action of the hippocampus is modulated by the
      mesolimbic serotonergic system via its interactions with the hippocampal or
      mesolimbic dopaminergic systems, or both.

PMID- 1980150
TI  - Functional effects of neural grafting in the mammalian central nervous system.
AB  - Grafts of fetal and nonfetal brain tissues have been successfully implanted into
      the mammalian central nervous system (CNS). The functional effects of neural
      grafting in the CNS of rodents and nonhuman primates in a variety of situations
      are reviewed. Research areas discussed included the effects of dopamine-rich
      grafts in animal models of Parkinson's disease and acetylcholine-rich grafts in
      animals with lesions of the cholinergic pathways to the neocortex and
      hippocampus. Graft effects also are examined in aged animals and genetic mutants.
      In addition, the effects of neural grafts on circadian rhythmicity, reproductive
      functions, and conditioned taste aversion are discussed. The beneficial
      functional effects of neural grafts and the possible mechanisms and implications
      for these effects are discussed, including the possibility that the CNS exhibits
      a regional biochemical specificity that influences the outcome of neural graft
      procedures.

PMID- 1980151
TI  - [First Puerto Rican Congress on Women and Health. Puerto Rico, November 9 and 10,
      1989. Proceedings].

PMID- 1980152
TI  - Pressor responses in rats following intravenous dynorphin A(1-13) administration
      are blocked by AVP-V1 receptor antagonism.
AB  - Hemodynamic (blood pressure and heart rate) experiments were conducted in
      conscious and/or anesthetized male Sprague-Dawley (S.D.), heterozygous and
      homozygous Brattleboro rats given intravenous (iv) dynorphin A(1-13), arginine
      vasopressin (AVP), norepinephrine (HCl, (NE) or sterile saline before and 10 min
      after an iv bolus injection of a specific receptor antagonist. These receptor
      blockers (kappa receptor antagonist Mr2266, alpha adrenoceptor antagonist
      phentolamine HCl or the AVP-V1 receptor antagonist d(CH2)5Tyr-(Me)AVP were given
      in equimolar concentrations (15 nmol/kg iv). In all conscious S.D. groups, iv
      injection of AVP (60 pmol/kg), NE (12.5 nmol/kg) and dynorphin A(1-13) (60
      nmol/kg) evoked significant increases in mean arterial pressure (MAP) associated
      with concomitant bradycardia. The hemodynamic responses to 'both' AVP and
      dynorphin A(1-13) were blocked if given subsequent to AVP-V1 administration but
      not following phentolamine or Mr2266 pretreatment. The pressor and bradycardic
      responses of conscious heterozygous and homozygous Brattleboro rats after iv AVP
      or dynorphin again were only blocked by the AVP-V1 receptor antagonist.
      Anesthetized heterozygous and homozygous Brattleboro rats again showed pressor
      responses following iv AVP, NE or dynorphin A(1-13) but with slight or no
      associated bradycardia. The rise in blood pressure with AVP 'and' dynorphin A(1
      13) in these groups also was only blocked by the d(CH2)5Tyr(Me)AVP antagonist.
      The results indicate that the pressor responses of rats given intravenous
      dynorphin A(1-13) involve the interaction of AVP-V1 receptors and suggest a
      functional interaction of these two neuropeptides in the modulation of vascular
      tone.

PMID- 1980153
TI  - [Diffuse interstitial pneumopathies caused by lentivirus (HIV-1) in humans and
      animals].
AB  - Lentiviruses belong to the retroviruses family (ie RNA viruses with reverse
      transcriptase activity); they induce inflammatory and/or degenerative slowly
      progressive diseases, affecting various organs. Some lentiviruses preferentially
      infect lymphocytes (HIV-1 and HIV-2, SIV and FIV) and are associated with
      infectious and tumoral disorders. Most lentiviruses induce a pulmonary disease,
      typically diffuse interstitial pneumonia. The visna/maedi-virus of sheep infects
      monocyte macrophage cells and the pulmonary lesions are macrophagic and
      neutrophilic alveolitis, lymphoid infiltration, myomatosis and interstitial
      fibrosis. Such pulmonary lesions are also induced by the goat and equine
      lentiviruses. In humans infected by HIV-1 or HIV-2, a diffuse interstitial lung
      disease also occurs; the histological findings are of alveolitis associated with
      lymphoid peribronchovascular infiltrates. The mechanism of formation of the
      lesions involves complex cellular interactions (especially between macrophage and
      lymphocyte, via cytokine production). These interactions are well modelled by
      small ruminant lentivirus induction of interstitial pneumonia.

PMID- 1980154
TI  - Etiology and epidemiology of acute respiratory tract infection in children in
      developing countries. Irvine, California, 20-22 October 1988. Proceedings.

PMID- 1980155
TI  - CD4+ T-cell clones from autoimmune thyroid tissue cannot be classified according
      to their lymphokine production.
AB  - In order to define whether CD4+ T cells from autoimmune and non-autoimmune
      thyroid tissue could be classified according to their mediator production,
      lymphokine production was studied in 63 thyroid-derived CD4+ T-cell clones from
      four patients with Graves' disease, one with Hashimoto's thyroiditis, and one
      with non-toxic goitre (9-12 clones per patient). The production of interleukin 2
      (IL-2), gamma interferon (IFN-gamma), tumour necrosis factor alpha (TNF-alpha),
      lymphotoxin (LT), interleukin 6 (IL-6) and transforming growth factor beta (TGF
      beta) was assessed at the mRNA level by slot-blot analysis in unstimulated clones
      as well as after activation with monoclonal anti-CD3 (OKT3) and IL-2. No
      lymphokine production was found in unstimulated clones, whereas 56% of the clones
      produced all six lymphokines simultaneously after stimulation. In the remaining
      44% usually not more than one lymphokine was missing from the complete panel.
      Lymphokine mRNA concentrations varied between different clones and different
      patients, but, in this small sample, not between the diseases from which the
      clones were originated. There was a significant correlation between IL-6, LT, and
      IL-2 mRNA levels and T-cell helper function, which was estimated by the
      stimulation of thyroid microsomal autoantibody production using autologous
      peripheral B cells. TGF-beta and IFN-gamma mRNA expression was unrelated to T
      cell help. The results demonstrate that intrathyroid T cells from autoimmune and
      non-autoimmune thyroid disorders cannot be classified according to their
      lymphokine production, unlike some results with in vitro-induced mouse T-cell
      clones, where two populations, Th1 and Th2, have been described. Single T cells
      are capable of producing a whole panel of lymphokines and thus are capable of
      triggering a multitude of different processes.

PMID- 1980156
TI  - Analysis of age-related degeneracy of T-cell repertoire: localized functional
      failure in CD8+ T cells.
AB  - The repertoire and frequency of alloreactive T cells in aged mice were examined
      by limiting dilution analysis of the mixed-lymphocyte reaction (MLR). Mice were
      aged in specific pathogen-free conditions up to 31 months, and MLR of their
      spleen cells under limiting dilution conditions was examined at various stages of
      ageing. The frequency of alloreactive T cells was found to decrease in mice more
      than 14 months of age, and the value reached about 1/3 of that of young mice of 2
      months of age. The slope analysis of cell dose-response curves of MLR indicated
      the existence of two interacting T-cell populations, i.e. CD4+ and CD8+,
      cooperation between which is required for the full manifestation of MLR in
      limiting dilution conditions. The decrease in the alloreactivity of aged spleen
      cells was ascribed to the selective functional loss of the CD8+ population,
      because the CD4+ but not the CD8+ T-cell fraction from aged mice could restore
      the limiting factor in MLR. The decrease in the cooperative activity of CD8+ T
      cells in allo-MLR starts much earlier than the decrease in the number of CD8+ T
      cells in the spleen.

PMID- 1980157
TI  - Immunological marker analysis of mitogen-induced proliferating lymphocytes using
      BrdU incorporation or screening of metaphases. Staphylococcal protein A is a
      potent mitogen for CD4+ lymphocytes.
AB  - The proliferative effects of the mitogens phytohaemagglutinin (PHA), concanavalin
      A (Con A), pokeweed mitogen (PWM), and staphylococcal protein A (SpA) were
      investigated using two different methods which enable immunological marker
      analysis of proliferating cells: either surface marker labelling followed by BrdU
      incorporation or screening of metaphases after surface marker labelling.
      Therefore peripheral blood mononuclear cells from six healthy volunteers were
      stimulated with these four mitogens. Both PHA and Con A gave rise to more CD8+
      than CD4+ proliferating cells. PHA, but not Con A, induced B-cell proliferation
      as well. PWM mainly caused T-cell proliferation. SpA also appeared to be a potent
      T-cell mitogen in addition to its capacity to induce B-cell proliferation.
      However, in contrast to the other mitogens SpA predominantly stimulated CD4+
      cells.

PMID- 1980158
TI  - Hot spots for growth hormone gene deletions in homologous regions outside of Alu
      repeats.
AB  - Familial growth hormone deficiency type 1A is an autosomal recessive disease
      caused by deletion of both growth hormone-1 (GH1) alleles. Ten patients from
      heterogeneous geographic origins showed differences in restriction fragment
      length polymorphism haplotypes in nondeleted regions that flanked GH1, suggesting
      that these deletions arose from independent unequal recombination events.
      Deoxyribonucleic acid (DNA) samples from nine of ten patients showed that
      crossovers occurred within 99% homologous, 594-base pair (bp) segments that
      flanked GH1. A DNA sample from one patient indicated that the crossover occurred
      within 454-bp segments that flanked GH1 and contained 274-bp repeats that are 98%
      homologous. Although Alu repeats, which are frequent sites of recombination, are
      adjacent to GH1, they were not involved in any of the recombination events
      studied. These results suggest that length and degree of DNA sequence homology
      are important in defining recombination sites that resulted in GH1 deletions.

PMID- 1980159
TI  - Localization and biosynthesis of functional thrombomodulin in human
      megakaryocytes and a human megakaryoblastic cell line (MEG-01).
AB  - The localization and biosynthesis of functional thrombomodulin (TM) on the cell
      surfaces of human platelets, megakaryocytes and a human megakaryoblastic cell
      line (MEG-01) were investigated. TM was demonstrated on the cell surfaces and in
      cytoplasms of human platelets, megakaryocytes and MEG-01 by an indirect
      immunofluorescent technique using monospecific rabbit anti-human TM serum.
      Immunoelectronmicroscopic analysis revealed that TM was localized in plasma
      membranes of MEG-01 cells as well as human megakaryocytes. 125I-monoclonal
      antithrombomodulin IgG binding assay showed that one MEG-01 cell possessed
      approximately 78,000 TM molecules on its cell surface. Thrombin-dependent protein
      C activating-cofactor activity was demonstrated on MEG-01 cells. Northern
      hybridization technique using cDNA probe of TM revealed that poly(A)(+)-RNA from
      MEG-01 cells showed a single band of 3.8 kb similar to that from human
      endothelial cells. These data suggest that human megakaryocytes synthesize
      functional TM, and thereby platelets possess TM on their surfaces. TM on
      platelets may participate in the activation of protein C at the site of a
      hemostatic plug.

PMID- 1980160
TI  - Restriction fragment length polymorphism (RFLP) of two HLA-B-associated
      transcripts (BATs) genes in healthy Danes.
AB  - The restriction fragment length polymorphism (RFLP) of the two human HLA-B
      associated transcripts (BATs) genes, BAT1 and BAT2, was investigated using 5
      different restriction enzymes and two human BAT1 and BAT2 cDNA probes. Two of the
      enzymes, NcoI and RsaI, revealed polymorphic patterns which were investigated in
      healthy Danes. The cDNA/restriction enzyme combination BAT1/NcoI identifies
      polymorphic bands at 12 kb, 8 kb, 2.5 kb, and 1.1 kb, while the BAT2/RsaI
      combination identifies polymorphic bands at 3.3 kb, 2.7 kb, 2.3 kb, and 0.9 kb.
      The frequencies of these markers were determined in 90 unrelated Danes. Co
      dominant segregation and allelic behavior was seen for the BAT1/NcoI 12 kb and 8
      kb bands and the BAT2/RsaI 2.7 kb and 2.3 kb bands, respectively. It is possible
      that the BAT2/RsaI 3.3 kb band represents a rare allele of the BAT2/RsaI system.
      The BAT2/RsaI 2.3 kb marker was strongly negatively associated with HLA-B8 and
      HLA-DR3 while there were no strong associations between the BAT1 and BAT2
      markers, but the BAT2/RsaI 2.7 kb marker was strongly positively associated with
      the TNF alpha/NcoI 5.5 kb marker, which in turn is positively associated with HLA
      B8 and HLA-DR3. The negative associations between the BAT2/RsaI 2.3 kb marker and
      HLA-B8 and HLA-DR3 raise the question as to whether this BAT allele may play a
      role in protecting against certain autoimmune diseases.

PMID- 1980161
TI  - Functional properties of HLA-DR-BON alleles associated with DQw5(w1) and with
      DQw7(w3): a family study.
AB  - Among the DR specificities undefined by serology, DR-BON is peculiar because RFLP
      cannot distinguish it from the well-defined allele DR1 even if the two
      specificities are very different functionally. The occurrence of two DR-BON-like
      alleles in the same family, one associated to the DQw5 split of DQw1 and the
      other associated to the DQw7 split of DQw3, enabled us to compare the properties
      of these alleles. The RFLP analysis showed a typical DR1-like picture for both
      alleles when probed with DR beta, but for one of the alleles the DQ beta probe
      gave a DQw7 pattern. Primary mixed lymphocyte cultures showed weak to moderate
      stimulation between cells from individuals identical for one haplotype and
      differing for the DR-blank haplotypes, but by test with cloned reagents we were
      not able to define differences between the two DR-blank molecules. Two
      dimensional gel electrophoresis and spot-test with a probe covering the third
      hypervariable region of the DRB1 gene showed no difference between the two
      alleles. We thus think that the two DR alleles are identical and that the
      stimulation observed in primary cultures probably is caused by incompatibility
      for DQ and DP or class I.

PMID- 1980162
TI  - The HLA-DR4-associated DQw8 allele is confined to HLA-DR3/DR4 heterozygous type I
      (insulin-dependent) diabetics.
AB  - The HLA-DR4 specificity revealed a relative risk of 8.5 (chi 2 = 99.6; p less
      than 0.0001) when 193 type I diabetics were compared to 305 controls. Prevalence
      of the HLA-DR4-associated DQ types, i.e. DQw7 and DQw8, were determined, using a
      restriction fragment length polymorphism (RFLP) typing that combines the
      probe/enzyme combinations DQB/Taq I and DQB/Bam HI. The HLA-DQw8 specificity was
      confined to HLA-DR3/DR4 heterozygous patients when compared to controls (chi 2 =
      4.9; p less than 0.025) or to all other DR4-heterozygous patients (chi 2 = 6.7; p
      less than 0.01). No association with HLA-DQw8 was seen in HLA-DR1/DR4 or HLA
      DR"X"/DR4 (X not equal to 1,3,4) heterozygous patients. Due to the excess of HLA
      DR3/DR4 patients the DQw8 allele is a risk factor in type I diabetics, but in HLA
      DR1/DR4 and DRX/DR4 heterozygotes one might suggest that DQB1 and DRB
      combinations confer HLA-associated susceptibility.

PMID- 1980163
TI  - HLA class II typing by digestion of PCR-amplified DNA with allele-specific
      restriction endonucleases will fail to unequivocally identify the genotypes of
      many homozygous and heterozygous individuals.
AB  - Recently, a new technique for HLA class II genotyping has been introduced, the
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
      method, claimed to be a practical alternative to conventional serological and
      cellular HLA class II typing (1-3). The PCR-RFLP technique is ingenious,
      relatively rapid and does not require hybridization with sequence-specific
      oligonucleotide probes. However, analysis of whether homozygous and heterozygous
      combinations of PCR-RFLP patterns for the various investigated HLA class II loci
      are unique or not unfortunately shows that only 19% of DRB homozygous and
      heterozygous combinations are unique. The figures for the DQA1, DQB and DPB loci
      are 56%, 29% and 65%, respectively. As not all nucleotide sequences analyzed in
      the above-mentioned studies (1-3) gave rise to unique PCR-RFLPs and as more
      sequences now are known, for the DRB1, DRB3, DRB5 and DPB1 loci (4), the
      frequencies of unique PCR-RFLP patterns for the different HLA class II loci will
      be reduced even further. Thus, the present analysis demonstrates that the PCR
      RFLP technique, performed as described in references 1-3, is not yet ready to be
      used for routine HLA class II genotyping. The resolution of the PCR-RFLP method
      can be improved by various modifications. However, the role of a modified PCR
      RFLP technique in HLA class II typing still remains to be shown.

PMID- 1980164
TI  - PCR-RFLP method holds great promise for complete HLA class II genotyping.

PMID- 1980165
TI  - [Oxidation of lactate in isolated rat heart mitochondria].
AB  - In unwashed mitochondria the oxidation of L-lactate (with NAD+) proceeds in
      presence of the added lactate dehydrogenase. The respiration is characterized by
      the high rate in state 4 and is stimulated by ADP. This process takes place in
      unwashed mitochondria and homogenate of the heart in absence of added lactate
      dehydrogenase. Oxidation of lactate with NAD+ is inhibited by rotenone. It has
      been also revealed that the oxidation of glutamate is insufficiently altered in
      presence of lactate (with NAD+) in unwashed mitochondria as compared with the
      washed ones. It is supposed that the stimulating effect of lactate with NAD+ on
      the mitochondria respiration is not so much a result of the membrane-damaged
      action as a result of oxidation of lactate dehydrogenase reaction products:
      phosphorylative oxidation of pyruvate and nonconjugated oxidation of NADH.
      Utilization of these products takes place in the main respiratory chain,
      including its first stage.

PMID- 1980166
TI  - Evidence of long distance airborne transmission of Aujeszky's disease
      (pseudorabies) virus.
AB  - Aujeszky's disease has been the subject of an eradication campaign in Denmark
      since 1980. A detailed knowledge of the virus strains present in the country was
      provided by restriction fragment analyses of older clinical isolates, and of
      isolates from all the virologically confirmed outbreaks since 1985. The
      introduction of foreign strains into southern border areas was demonstrated
      during the winters of 1984/85, 1986/87 and 1987/88. An epizootic during the
      winter of 1987/88 was shown to correlate with an unusual predominance of
      southerly winds. Both conventional and specific pathogen free herds became
      infected. A herd level case-control analysis of the outbreaks during the winter
      of 1987/88 revealed that there was a positive correlation between the risk of
      infection and the size of the herd. The observations support the hypothesis of
      airborne transmission of the disease.

PMID- 1980167
TI  - Immunohistochemical investigation and northern blot analysis of c-erB-2
      expression in normal, premalignant and malignant tissues of the corpus and cervix
      uteri.
AB  - Seventy specimens of normal endometrium (n = 13) and cervix (n = 12), endometrial
      hyperplasia (n = 4), cervical dysplasia (n = 20), endometrial (n = 11) and
      cervical carcinoma (n = 8) and uterine metastases of mammary carcinomas (n = 2)
      have been analysed for c-erB-2 expression with immunohistochemistry employing a
      monoclonal anti ERBB-2 antibody and Northern-blot hybridization using single
      stranded RNA probes. In comparison with the c-erbB-2 mRNA expression level found
      in normal samples, two advanced and poorly differentiated endometrial
      adenocarcinomas (FIGO IV) and two ductal mammary carcinomas which had
      metastasized to the uterus, together with three carcinomas in situ of the cervix,
      showed c-erbB-2 enhanced transcription level. All other endometrial samples
      including adenomatous hyperplasia and nine endometrial carcinomas (FIGO I), and
      all other lesions of squamous epithelial origin displayed transcriptional
      activities at or below the baseline level. Immunohistochemical study of ERBB-2
      protein expression showed staining in most samples, although different in
      distribution and intensity. Staining of endometrial glands was seen in unevenly
      distributed cells or cell clusters. In contrast, for endocervical glands,
      labelling was observed distinctly on basally located cells (reserve cells) and at
      the subapical side of luminal cells. Faint labelling of the basal cell layer was
      also observed in squamous epithelia. It was more pronounced in severe cervical
      dysplasia and carcinoma in situ. In carcinomas of glandular origin,
      dedifferentiation was accompanied by an increase in cytoplasmic labelling,
      whereas the intensity of staining was not related to differentiation in squamous
      cell carcinomas. While data derived from Northern blots are suggestive of c-erbB
      2 overexpression to indicate an advanced and dedifferentiated state of tumours of
      glandular origin, staining with an anti-ERBB-2 antibody occurred in both normal
      and atypical squamous and glandular epithelia and may indicate regular
      proliferation and/or differentiation-associated events.

PMID- 1980169
TI  - Abundant dendritic cells express HLA-DR in pleomorphic adenomas.
AB  - Most pleomorphic adenomas were found to contain abundant dendritic cells (DC)
      with major histocompatibility complex (MHC) class II (HLA-DR) expression. Their
      immunohistochemical staining features were suggestive of dendritic histiocytic
      cells. Extensive phenotypic characterization by two-colour immunofluorescence
      staining for various cell markers was performed. The DC expressed both HLA class
      I and II determinants, vimentin, S-100 protein, and various monocyte-related
      markers (10G11, 3D10, 7G5 or CD11a, 8C2) but were negative for leucocyte common
      antigen (CD45), Leu-6 (CD1), and the myelomonocytic L1 antigen. Characterization
      of HLA-DR positive DC isolated by an immunomagnetic bead method confirmed the
      immunohistochemical staining pattern that corresponds to the phenotype of
      interdigitating cells. Morphological and immunological implications of the
      abundant presence of these cells in pleomorphic adenomas are discussed.

PMID- 1980168
TI  - Tumor infiltrating leukocytes (tils) during progressive tumor growth and BCG
      mediated tumor regression.
AB  - Tumor regression was induced by intralesional injection with BCG, 7 days after
      inoculation of line 10 hepatocellular carcinoma cells into strain 2 guinea pigs.
      Tumor-infiltrating leukocytes (TILS) were characterized immunohistochemically
      with 11 monoclonal antibodies (MoAbs) during the induction phase of line 10
      immunity, and during immune-mediated regression of the tumor, at days 12 and 28
      after tumor cell inoculation, respectively. At day 5 after BCG-injection (day 12
      after tumor cell inoculation), there were no major differences between the TIL
      subpopulations of the BCG-treated and untreated tumors. The TILS were mainly T
      cells, as identified by MoAbs against Pan T-cells (CT5), T-cytotoxic/suppressor
      cells (CT6) and T-helper/inducer cells (H155). A limited number of macrophages
      was also present. However, at day 21 after BCG-treatment (28 days after tumor
      cell inoculation), the fibrous stroma was increased dramatically in most of the
      BCG-treated tumors, and as a result, the tumor cell islets were smaller than in
      control tumors. In the BCG treated tumors, the numbers of T-cells and macrophages
      were increased. In growing and regressing tumors, MHC class I and II antigens
      were strongly expressed in TILS and in the tumor stroma. Line 10 tumor cells
      prior to inoculation expressed no MHC class I or II antigens. In the centers of
      the tumor islets at days 12 and 28, expression of these antigens was not found.
      However, MHC class I and II antigens were expressed on tumor cells at sites where
      they lay close to the fibrous stroma or TILS. This observation was made in
      progressively growing tumors and was most apparent in BCG-treated tumors.

PMID- 1980170
TI  - The age at onset of diabetes influences functional and structural changes in the
      pituitary-thyroid axis of streptozocin-diabetic male rats.
AB  - Severe structural changes leading to marked alterations in secretory activity are
      known to occur in the pituitary-thyroid axis 1 month after induction of
      postpuberal streptozocin (SZ)-diabetes. However, SZ-diabetic rats of different
      age groups have not been compared, nor has the maturity of the pituitary and
      thyroid glands at the onset of diabetes been correlated with the type and
      evolution of functional and structural changes. We thus induced diabetes in 1
      month (prepuberal of 3-month (postpuberal) old male rats and compared diabetic
      with control groups 4 and 8 months after SZ or saline injection. We determined:
      1) pituitary and thyroid weights, 2) the basal plasma TSH, T3, and T4
      concentrations, and 3) several morphometrical measurements in the pituitary and
      thyroid glands. After 4 months, 1) the pituitary and thyroid weights were
      decreased, 2) plasma TSH and T3 were unchanged, plasma T4 was reduced. and 3) the
      number of thyrotropes, degenerative changes of follicle cells, and colloid area
      were increased, the follicle cell height as well as the number of fused cold
      follicles decreased, and the follicle area was unchanged in diabetic compared
      with control rats. The lesions were more conspicuous in pre- than in postpuberal
      diabetic animals. After 8 months, plasma TSH, T3, and T4 were decreased in
      diabetic compared with control rats. Except for the increased colloid area, all
      other lesions were similar, though more severe in prepuberal diabetic rats after
      8 than 4 months. Few changes were found in postpuberal diabetic rats.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1980172
TI  - Innervation and maturation of muscular tissue in testicular teratomas in strain
      129/Sv-ter mice.
AB  - In strain 129/Sv-ter mice, teratomas develop spontaneously during the 13th day of
      gestation. These testicular germ cell tumors exhibit characteristics of different
      germ layers closely resembling normal embryonic tissue. We investigated the
      interrelationship between nervous and muscular tissues (often found side by side)
      in teratomas of 4-week-old 129/Sv-ter mice. In well-differentiated mouse
      teratomas, histochemically and immunohistochemically distinct muscle fiber types
      could be distinguished, but not with all reactions. According to its aerobic
      oxidative capacity, teratoma muscle tissue was comparable with normal muscles.
      However, with respect to myosin-related properties, fiber type differentiation
      was incomplete. The muscle fibers - generally arranged in bundles - contained one
      centrally located endplate which was contacted mostly by a single nerve terminal.
      From this, proper endplate zones within the fiber bundles were formed.
      Occasionally "type grouping" was encountered, suggesting collateral axonal
      branching paralleled by synapse elimination. Together with the earlier in vivo
      observation of muscular contractions, we assume that teratoma muscle fibers are
      innervated by nerve cells (within the nervous tissue compartments) corresponding
      to spinal motoneurons. Thus, myogenesis, maturation and innervation of skeletal
      muscular tissue in mouse teratomas are largely comparable to normal development.

PMID- 1980171
TI  - Effect of nitrendipine on cardiac and renal lesions and arterial hypertrophy.
      Protective effect of a low dose of calcium antagonist in deoxycorticosterone
      induced hypertensive rats.
AB  - A low dose of nitrendipine (1 mg/kg twice daily) ameliorated the percent
      incidence and severity of vascular lesions in the kidney and heart induced by
      deoxycorticosterone (DOC). Less protection was offered by administration of 1
      mg/kg of the calcium antagonist once daily. A lower dose of the antagonist (0.5
      mg/kg) administered twice daily produced almost no protection against myocardial
      scars, but the percent incidence and severity of renal tubular casts and
      glomerular changes were similar to those following injection of 1 mg/kg of the
      antagonist twice daily. DOC induced hypertrophy of the media in aorta, coronary
      artery and renal interlobular artery and renal arteriole. Neither 1 mg/kg once or
      twice daily nor 0.5 mg twice daily of calcium antagonist modified the hypertrophy
      of the arterial vasculature in the hypertensive DOC group. We conclude that a low
      dose of the calcium antagonist dissociates at least in part lesions but not
      hypertrophy from the increased systolic blood pressure, because the antagonist
      protects against vascular lesions induced by the hypertension. The antagonist
      likely acts on the endothelial cell of the vessels alone or combined with an
      effect on the vascular smooth muscle cells.

PMID- 1980173
TI  - Effects of vitamin A-deficiency and inflammation on the conducting airway
      epithelium of Syrian golden hamsters.
AB  - The effects of vitamin A-deficiency and inflammation were studied in the
      conducting airways of Syrian golden hamsters. An important goal of the study was
      to characterize epithelial changes that occur early in vitamin A-deficiency, that
      might precede yet predispose to infection, and precipitate inflammatory changes
      in the lungs. Age-matched vitamin A-replete control and vitamin A-deprived
      hamsters were killed at 33 days of age (preweight-plateau); at 41 days of age
      (weight plateau-early weight loss); and at 48-55 days of age (prolonged weight
      plateau followed by weight loss). A tablet containing bromodeoxyuridine (BrdU)
      was implanted subcutaneously into each hamster 7 h before it was killed. No
      changes were seen in the conducting airway epithelium of vitamin A-deprived
      hamsters in the preweight plateau. However, labelling of secretory cells for BrdU
      was reduced 6-7 fold in the epithelium lining the lobar bronchus (p less than
      0.0002) and the bronchioles (p less than 0.0001), and the proportions of ciliated
      cells were decreased (p less than 0.0001) at both airway levels in vitamin A
      deficient hamsters in the weight plateau-early weight loss stage. Changes in
      cellular morphology were minimal in the intrapulmonary airway epithelium at this
      time but a few small focal patches of epidermoid metaplasia were seen in the
      tracheal epithelium. Small foci of inflammation were closely associated with the
      airways in the weight plateau, and the inflammation became more widespread when
      the deficiency was prolonged. The results suggest that the defense of the lungs
      to infection was impaired initially in the vitamin A-deficient hamsters by a
      widespread reduction in the numbers of ciliated cells throughout the epithelium
      of the conducting airways (trachea, bronchi, bronchioles). At the foci of
      inflammation, labelling of epithelial secretory cells for BrdU was greatly
      increased at all airway levels. A highly stratified cornifying epidermoid
      metaplasia developed in the tracheal epithelium, and goblet cell metaplasia
      developed in the cranial portion of the lobar bronchus, in association with
      submucosal inflammation. Goblet cell metaplasia appeared to be the only
      abnormality that was not reversed when vitamin A was restored to the diet.

PMID- 1980174
TI  - Immunohistochemical demonstration of cytochrome P-450 monooxygenase in
      regenerating tracheal epithelium: a recapitulation of fetal development.
AB  - The cytochrome P-450 monooxygenase enzymes, NADPH-reductase and form 2, were
      demonstrated immunohistochemically in hamster tracheal epithelium that was
      regenerating after mechanical injury. Bromodeoxyuridine (BrdU), a thymidine
      analogue, was used to map the location and extent of the wound sites between 8
      and 144 h post-injury. In the control and non-wounded areas of the epithelium,
      the secretory cells were labelled for the monooxygenase enzymes. Label was
      heaviest in the apical cytoplasm of these columnar cells. At 8 h, secretory cells
      at the wound margins migrated to cover the wound sites, becoming progressively
      flattened. Reaction product for monooxygenase enzymes was strong in these flat
      cells but immunolabelling for BrdU was very low. At 24 h many cells at the wound
      sites were labelled for BrdU (indicative of a high rate of cell division). Some
      cells were labelled for monooxygenase but many were not stained at this time. At
      48 and 72 h post-injury, none of the cells within the wound sites (regenerating
      epithelium) were stained. Immunochemical labelling for the monooxygenase enzymes
      was restored to the nascent secretory cells as they differentiated in the wound
      sites, beginning at 96 h post-injury. Labelling was stronger at 120 and 144 h
      post-injury, comparable to that in the control epithelium. The observations
      suggest that the monooxygenase enzymes were retained by the secretory cells in
      the wound sites before they divided but were lost from their progeny. Then, the
      temporal sequence of monooxygenase expression was similar to the pattern of
      differentiation of nascent secretory cells during fetal development of the
      tracheal epithelium.

PMID- 1980176
TI  - Cell culture amplification of a defective Marek's disease virus.
AB  - A highly amplified 4-kb EcoRI fragment was present in DNA isolated from high cell
      culture passaged stocks (greater than 93 passages) of 281MI/1, a serotype 2
      Marek's disease virus (MDV). The isolated 4-kb fragment is amplified in the
      presence of MDV, replicating as a high molecular weight, head-to-tail concatemer.
      When the 4-kb fragment was cloned into pUC18 and cotransfected with MDV DNA into
      chicken embryo fibroblast cells, the plasmid clone also replicated as a high
      molecular weight concatemer.

PMID- 1980175
TI  - Cloning and mapping of the potato virus Y genome and its in vitro expression.
AB  - Full-length cDNA of genomic RNA of potato virus Y (PVY) was cloned in one piece
      into a lambda vector. The order of the EcoRI and SalI fragments of the inserted
      cDNA was determined. This is the first report of the cloning of a long,
      expressible, potyvirus genome. The availability of such a clone is a prerequisite
      for any further study of the molecular biology of this group of viruses, as they
      are expressed into a self-processed primary polyprotein.

PMID- 1980178
TI  - [Usefulness and cogency of gene probes in paternity questions (Personal
      experiences: 1989/90].
AB  - In cases of disputed parentage usually more than 20 polymorphic systems (red and
      white cell antigens, serum markers and enzyme markers) have to be analyzed using
      a battery of different techniques. A more recent method involving analysis of
      restriction fragment length polymorphism in highly polymorphic genes allows
      assignment of offspring to their parents. To test the latter method, 28 paternity
      cases were studied in parallel using conventional systems and detection of RFLPs
      of probes MS 1, MS 31, MS 43, and g 3, developed by Jeffreys et al. Furthermore,
      the cogency of exclusion of parentage, the average power of exclusion and the
      probability of parentage is calculated using published mutation rates and gene
      frequencies of the four probes. In conclusion, use of the four gene probes has
      both theoretically and practically turned out to be a powerful method for
      parentage testing.

PMID- 1980177
TI  - Two-step transformation of rat 3Y1 cells by the adenovirus E1A and E1B genes.
AB  - The transformation of rodent cells by the adenovirus E1A and E1B genes was very
      efficient when these genes were physically linked. When they were cleaved, the
      transformation became very inefficient. To clarify this difference, the chimeric
      E1B genes in which either the adenovirus enhancer or the human beta-actin
      promoter was linked to the 5' side of the E1B gene were introduced into rat 3Y1
      cells. The saturation density of these cell lines (eB or APrB) was similar to
      that of parental 3Y1 cells. When eB or APrB cell lines were supertransfected with
      the E1A gene, discrete dense foci were developed after 5-6 weeks, while the
      supertransfection of 3Y1 derivative cell lines, in which the enhancer-unlinked
      E1B gene was introduced, did not develop any dense foci. Analysis of the E1A and
      E1B transcripts in these cell lines indicated that the E1B gene is efficiently
      expressed in the presence of the E1A gene products if the enhancer is linked to
      the E1B gene and that an increased level of E1B proteins is required for an
      efficient expression of the E1A gene. These results indicated that E1A and E1B
      genes in separate pieces of DNA are capable of cooperatively transforming 3Y1
      cells if appropriate cis-acting elements are attached and high-level expressions
      are achieved.

PMID- 1980179
TI  - Aspiration pneumonitis: risk factors and management of the critically ill
      patient.
AB  - Pulmonary aspiration of gastric contents is a significant source of patient
      morbidity, mortality, and increased healthcare costs. Prevention by identifying
      patients at risk for aspiration and initiating prophylaxis is the most effective
      method of reducing complications associated with aspiration pneumonitis. H2
      receptor antagonists are among the best prophylactic agents because of their
      efficacy in reducing gastric acidity and their convenience of administration.

PMID- 1980180
TI  - Achieving pH control in the critically ill patient: the role of continuous
      infusion of H2-receptor antagonists.
AB  - Stress-related gastric mucosal damage is a common occurrence in intensive care
      unit (ICU) patients. Because of the significant morbidity and mortality
      associated with this mucosal damage, many ICU patients routinely receive
      prophylactic therapy, usually with histamine H2-receptor antagonists (H2RAs).
      Gastric acid secretion occurs in a circadian pattern, with late afternoon and
      evening surges. H2RAs by continuous infusion may control this uneven pattern of
      secretion more effectively than H2RAs given by bolus injection. More studies are
      needed to identify the target ICU population for prophylactic treatment.

PMID- 1980181
TI  - Controlling gastric pH: the impact of newer agents on the critically ill patient.
AB  - The critically ill patient is at increased risk for developing erosive injury of
      the stomach, duodenum, and esophagus. To date, the most effective way to prevent
      and treat this problem is by assuring excellent intensive care support and by
      reducing gastric acid secretion. The histamine H2-receptor antagonists (H2RAs)
      are effective in both prevention and treatment of such gastric mucosal injury.
      Newer agents are available that have potential for use in this setting, although
      none have been studied as extensively in critically ill patients as have the
      H2RAs. These new agents include proglumide, pirenzepine, misoprostol, omeprazole,
      and somatostatin. To date, only the latter has been extensively studied in
      critically ill patients. Omeprazole, which suppresses acid very effectively, may
      be problematic in the critically ill, limited by its oral dosage form, acid
      labile properties, and potential drug interactions.

PMID- 1980182
TI  - Hemodynamic effects of H2-receptor antagonists.
AB  - Histamine H2-receptor antagonists (H2RAs) often are administered to intensive
      care unit patients in an attempt to reduce gastric acidity and to prevent stress
      related mucosal damage. These agents have an extremely low overall incidence and
      severity of adverse reactions; however, hemodynamically significant hypotension
      has been noted. Clinical studies with rapidly administered intravenous cimetidine
      in critically ill patients have demonstrated a depression in blood pressure in up
      to 75 percent of patients. Ranitidine, also studied in this setting, does not
      appear to induce similar hemodynamic changes. The newer H2RAs, famotidine and
      nizatidine, have not been evaluated in critically ill patients.

PMID- 1980183
TI  - Overview of the safety profile of the H2-receptor antagonists.
AB  - Reports of adverse drug reactions due to histamine H2-receptor antagonists
      (H2RAs) are rare considering their wide usage. Cimetidine produces central
      nervous system and endocrine toxicities more often than other H2RAs. Drug-drug
      interactions are of potentially greater concern with H2RAs, especially because
      the critically ill patient routinely receives many drugs. H2RAs may alter the
      absorption, metabolism, or renal excretion of concurrently administered drugs.
      Gastrointestinal absorption of drugs, such as ketoconazole, that dissolve poorly
      in the absence of adequate acid may be reduced. Inhibition of hepatic oxidative
      drug metabolism of agents such as warfarin, theophylline, and phenytoin, is
      primarily a problem with cimetidine. Adverse effects will be seen in predisposed
      individuals and the time course will depend on the pharmacokinetics of the object
      drug. The other H2RAs are less likely to inhibit drug metabolism and affect renal
      clearance of procainamide than is cimetidine.

PMID- 1980185
TI  - [Anxiety and disorders caused by anxiety].

PMID- 1980184
TI  - Pathophysiology, monitoring, and management of the ventilator-dependent patient:
      considerations for drug therapy, emphasis on stress ulcer prophylaxis.
AB  - Adult respiratory distress syndrome (ARDS), or noncardiac pulmonary edema, is a
      form of acute hypoxemic respiratory failure. The goals of treatment for patients
      with ARDS are to provide supportive therapy, to reverse the underlying etiology
      or pathology, and to prevent subsequent complications. Supportive therapy
      consists of supplemental oxygen, positive end-expiratory pressure, and, often,
      mechanical ventilation. The reversal of the underlying pathology varies according
      to the etiologic origin of ARDS. Complications from ARDS include stress ulcers,
      which occur when gastric aggressive and defensive functions become unbalanced.
      Antacids and cytoprotective agents are used for stress ulcer prophylaxis, but
      histamine H2-receptor antagonists are now regarded as the standard of care.
      Because all the marketed H2-receptor antagonists are efficacious, choice of the
      agent is based on the adverse effect profile and drug interactions. No definitive
      data currently exist linking stress ulcer prophylaxis regimens that raise
      intragastric pH to a significant risk for nosocomial pneumonia.

PMID- 1980187
TI  - [Adrenergic betareceptors and cardiac insufficiency].
AB  - Noradrenergic sympathetic tone is always increased in chronic left ventricular
      failure of which it is one of the main compensatory mechanisms. Beta-1-adrenergic
      stimulation increases the heart rate and left ventricular contractility. However,
      the efficacy of this "compensatory" mechanism is limited on the one hand by the
      energetic cost of inotropic stimulation and, on the other hand, by the phenomenon
      of desensitisation and down-regulation of myocardial beta-1-receptors during
      intense and prolonged noradrenergic stimulation as observed in chronic cardiac
      failure. These physiopathological concepts raise the question of the indications
      of drugs affecting betareceptors in cardiac failure. Positive inotropic beta
      mimetics can only be used during short periods of acute decompensation: low dose
      betablocker therapy protects the betareceptors from the phenomenon of
      desensitisation and seem to exert a beneficial action in this way in some cases
      of cardiac failure; these preliminary results require confirmation by large scale
      controlled therapeutic trials. Finally, a new pharmacological class of drugs, the
      beta-1 adrenergic partial agonists, seems to be useful in the management of
      moderate degrees of cardiac failure due to ischemic heart disease.

PMID- 1980186
TI  - HIV-1 infection in a cohort of haemophilic patients.
AB  - The course of HIV infection in 53 haemophilic patients aged 5-20 years was
      evaluated by clinical examination and laboratory tests. During the evaluation
      time (median 30 months) two patients died of AIDS and 32 patients (60%)
      deteriorated when assessed by the Brodt-Helm classification. Nineteen patients
      (37%) had decreased absolute helper cell counts (less than 500 CD4 positive
      cells/microliters), and 45 patients (87%) had reduced helper cell to lymphocyte
      ratios (less than 0.35). HIV-1 was isolated from peripheral lymphocytes in 29 of
      46 patients. As the disease progressed the number of positive viral cultures
      increased. Considerable progression of the HIV infection was seen in haemophilic
      children and adolescents during the median evaluation period of 30 months. The
      transition from symptomless HIV infection to immunodeficiency was easily
      recognised. A lowered ratio of helper cells to lymphocytes seems to be a useful
      marker of the beginning of the deterioration of the immune system.

PMID- 1980188
TI  - [Treatment of arrhythmias in chronic cardiac insufficiency].
AB  - Arrhythmias are frequent and associated with a poor prognosis, especially when
      they arise from the ventricle. Although the correction of predisposing factors
      and improvement of hemodynamic conditions are essential, the use of
      antiarrhythmic drugs in this context poses problems. The treatment of even
      complex ventricular extrasystoles has not been shown to effectively prevent the
      serious arrhythmias responsible for sudden death. Depression of left ventricular
      function and: Or proarrhythmic effects of antiarrhythmic therapy in some
      patients, probably offset the benefits observed in others. The treatment of
      atrial arrhythmias remains traditional: reduction by drugs or electrotherapy and
      prevention of recurrences, or simply slowing the ventricular response. Sustained
      ventricular tachycardia and resuscitated ventricular fibrillation should be
      managed more aggressively, not by empirical antiarrhythmic treatment but by
      medical therapy guided by the results of electrophysiological studies, and, when
      this fails, by non-medical treatment: fulguration, implantable defibrillator,
      antiarrhythmic surgery, or even cardiac transplantation.

PMID- 1980189
TI  - Low molecular weight alanine aminopeptidase of human serum: separation and some
      characteristics.
AB  - An alanine aminopeptidase, which has characteristics different from those of
      known alanine cleaving aminopeptidases, was partially purified from human serum
      by Sephadex G-200 gel chromatography and DEAE Sepharose column chromatography.
      The enzyme exhibited a molecular weight of 58,000 by gel chromatography. The pI
      of the enzyme was 5.0, and it was inactivated at 60 degrees C in 20 min. The
      enzyme readily hydrolyzed L-alanine beta-naphthylamide, but hardly hydrolyzed the
      other tested beta-naphthylamides. The Km value for L-alanine beta-naphthylamide
      was 0.29 mM, the pH optimum 7.5. The activity of the enzyme was enhanced by
      chloride ions and by sulfhydryl ethylenediaminetetraacetic compounds, and was
      inhibited by sulfhydryl blocking ethylenediaminetetraacetic agents, and bestatin.
      Furthermore, 1.10 phenanthroline and ethylenediaminetetraacetic acid were
      inhibitory, and the activity was restored by CoCl2 and ZnCl2. The enzyme is a
      chloride-enhanced thiol dependent metalloaminopeptidase.

PMID- 1980190
TI  - [A membrane-bound alanine aminopeptidase from Acinetobacter calcoaceticus. 3.
      Inhibition of the enzyme].
AB  - The alanine aminopeptidase from Acinetobacter calcoaceticus is inhibited by SH
      reagents like p-hydroxymercuribenzote, Ellman's reagent, N-bromosuccinimide, and
      metal chelating agents like 1,10-phenanthroline. The AAP is competitively
      inhibited by L-amino acids such as leucine, phenylalanine, and valine having
      hydrophobic side chains. Bacitracin (Ki = 2.0.10(-6) mol/l) inhibits AAP stronger
      than puromycin (Ki = 8.0.10(-6) mol/l). In contrast, the Aeromonas aminopeptidase
      (EC 3.4.11.10) is stronger inhibited by bestatin (Ki = 1.8.10(-8) mol/l) than the
      membrane-bound AAP from Acinetobacter calcoaceticus. However, the binding of
      bestatin by both membrane-bound enzymes. Acinetobacter-AAP and microsomal
      aminopeptidase M (EC 3.4.11.2), with Ki values of 8.10(-6) mol/l is in the same
      range.

PMID- 1980191
TI  - Relationships between octanol-water partition data, chromatographic indices and
      their dependence on pH in a set of beta-adrenoceptor blocking agents.
AB  - A thorough investigation on the dependence of octanol/water distribution
      coefficients (log D) of basic and amphiprotic beta-blocker drugs on pH and pKa
      values has been carried out. An attempt is made to clarify the factors which
      govern the chromatographic parameters (log k') in reversed-phase high performance
      liquid chromatography (RPLC) in terms of chemical structure and of distribution
      coefficients. The correlations between log D and log k' of different compounds
      show that the bulkiness and the branching of nitrogen substituent are controlling
      factors in RPLC measurements. Finally, an ion pair chromatographic system is
      considered for the prediction of octanol/water partition coefficients.

PMID- 1980192
TI  - Nucleotide sequences and novel structural features of human and Chinese hamster
      hsp60 (chaperonin) gene families.
AB  - A number of clones that specifically hybridize to the human hsp60 cDNA
      (chaperonin protein; GroEL homolog) were isolated from human and Chinese hamster
      ovary cell genomic libraries. DNA sequence analysis shows that one of these
      clones, pGem-10, is completely homologous to the human hsp60 cDNA (in both coding
      and noncoding regions) with no intervening sequences. The other human clones
      analyzed were all nonfunctional pseudogenes containing numerous small additions,
      deletions, and base substitutions, but no introns. On the basis of sequence data,
      six different hsp60 pseudogenes were identified in human cells. In addition, we
      also cloned and completely sequenced a genomic clone from CHO cells. This clone,
      which was also a pseudogene, contained a small 87-nucleotide intron near the 3'
      end. Southern blot analysis of human, mouse, and Chinese hamster DNA, digested
      with unique restriction enzymes (no sites in cDNA), indicates the presence of
      about 8-12 genes for hsp60 in the vertebrate genomes. The sequence data, however,
      suggest that most of these genes, except one (per haploid genome), are likely to
      be nonfunctional pseudogenes.

PMID- 1980193
TI  - Cloning and characterization of a novel member of the cytochrome P450 subfamily
      IVA in rat prostate.
AB  - To isolate cDNAs for forms of cytochrome P450 from rat prostate, a lambda gt11
      cDNA library from this tissue was screened with a mixture of oligonucleotide
      probes directed against the conserved heme binding region of different P450
      isozymes. A cDNA clone (PP1) encoding a part of a novel form of cytochrome P450
      was isolated and the deduced amino acid sequence showed 76% identity with
      cytochrome P450 IVA1, indicating that PP1 is a member of the same subfamily.
      Northern blot analysis of total RNA from prostates of untreated rats revealed
      that two mRNAs of approximately 2.8 and 2.2 kb hybridize to PP1. The level of
      mRNA was induced fivefold above the level in intact animals by androgen treatment
      of castrated rats. Analysis of poly(A)+RNA levels in different tissues on
      Northern blots showed high constitutive expression of PP1 in the kidney, but no
      signal was detectable with RNA from liver; a weak signal was detected in the
      retina. Subsequent screening of a rat kidney cDNA library led to the isolation of
      the full-length clone KP1, which differs from Pp1 only in three nucleotide
      positions. KP1 is 1,957 bp long and contains a 1,527-bp-long open reading frame
      encoding a protein of 508 amino acids. In situ hybridization of rat kidney
      sections with PP1 showed that this P450 form is expressed in the outer stripe of
      the outer medulla, indicating its localization in the proximal tubules.

PMID- 1980194
TI  - The Sixth International Conference on AIDS. San Francisco, California. June 20
      25, 1990.

PMID- 1980195
TI  - The localization of somatostatin-like immunoreactivity in the alimentary tract of
      the sheep with observations on the effect of an infection with the parasite
      Haemonchus contortus.
AB  - Cells containing somatostatin immunoreactivity were localized in the alimentary
      tract of parasite-free sheep by indirect immunocytochemistry, using an antiserum
      raised to ovine somatostatin. Nerve fibres showing somatostatin-like
      immunoreactivity were identified in the oesophagus, reticulum wall and groove,
      rumen pillar and wall, omasum sulcus and abomasum. Varicose fibres were found in
      the myenteric plexuses of the duodenum, jejunum, ileum and colon. The greatest
      distribution of endocrine cells (99 cells mm-2) was found in the antrum of the
      abomasum with 47, 29, 12 and 6 cells mm-2 respectively in the fundus, the first
      part of the duodenum, mid-jejunum and ileum. Some of the parasite-free sheep
      which had never experienced infection with larvae of the abomasal nematode,
      Haemonchus contortus, were paired with similar sheep in an experiment to
      investigate the effect of parasitism on nitrogen metabolism in the small
      intestine. The protocol of this experiment required observations before and after
      parasite infection, with final observations 2 weeks after removal of the
      infection by treatment with an anthelmintic drug. The sheep were then killed and
      tissues taken from each paired animal. Tissues from the recently parasitized
      sheep showed increases of D cells in the fundus and antrum of the abomasum. At
      present it is not clear if these increases were related to parasitism, per se, or
      were the post-treatment indicators of healing and recovery from infection with
      parasite larvae.

PMID- 1980196
TI  - A method to analyze allele-specific methylation.
AB  - We have developed a method to analyze the methylation patterns of individual
      alleles of a gene. The target gene must have alleles identifiable by restriction
      fragment length polymorphism analysis. The method involves separation of the
      alleles after digestion by restriction enzyme digestion and electrophoresis,
      followed by recovery from the gel on ion-exchange paper. Methylation analysis can
      be done on the separate alleles by Southern blot after digestion by methylation
      sensitive enzymes. As an example, we studied human c-Ha-ras-1 and showed that the
      methylation patterns of different alleles are stable and inherited. The method
      can be applied to the study of inheritance and methylation in genes where alleles
      can be identified by restriction fragment length polymorphism.

PMID- 1980198
TI  - Third Symposium on Lactic Acid Bacteria--Genetics, Metabolism and Applications.
      Wageningen, The Netherlands, 17-21 SEptember 1990. Proceedings.

PMID- 1980197
TI  - Maternally administered esmolol decreases fetal as well as maternal heart rate.
AB  - Fetal heart rate was monitored during the administration of esmolol 100
      micrograms/kg/min to a 36-year-old, 29-week pregnant woman who was undergoing
      craniotomy for surgical treatment of six cerebral aneurysms. During stable
      general anesthesia, sodium nitroprusside was administered to induce moderate
      hypotension; at the same time, esmolol was infused to control maternal
      tachycardia. Within minutes after starting the esmolol infusion, maternal heart
      rate decreased from 100 beats/minute to 65 beats/minute, and fetal heart rate
      decreased from 160 beats/minute to 130 beats/minute. Upon termination of the
      infusion 3 hours later, both maternal and fetal heart rate returned to
      preinfusion values. No adverse effects of esmolol infusion were noted in the
      mother or fetus.

PMID- 1980199
TI  - Up tempo, down tempo.

PMID- 1980200
TI  - Selective beta-adrenoceptor partial agonist effects of pindolol and xamoterol on
      skeletal muscle assessed by plasma creatine kinase changes in healthy subjects.
AB  - 1. The effects of selective beta-adrenoceptor partial agonist activity on plasma
      creatine kinase (CK) and skeletal muscle symptoms were studied in normal
      volunteers. 2. A drug with beta 1-selective partial agonist activity (xamoterol)
      and one with partial agonist activity acting mainly through beta 2-adrenoceptors
      (pindolol) were each given for 3 weeks in a randomised double-blind crossover
      study in 10 subjects. Five additional subjects received only one drug. Plasma CK
      levels were monitored during a baseline placebo run-in phase, the active
      treatment period and a placebo washout phase which continued until CK levels
      returned to baseline. 3. The degree of beta-adrenoceptor antagonism was
      determined by the inhibition of exercise-induced tachycardia and was similar for
      the two drug doses used. 4. During pindolol administration plasma CK levels rose
      compared with pretreatment baseline levels and with levels during xamoterol
      administration which did not rise. After pindolol was withdrawn CK levels reached
      higher peaks in some subjects after 1-5 days. 5. Muscle cramps were reported by
      five subjects during pindolol administration and by one of these subjects but to
      a lesser extent during xamoterol administration. 6. Pindolol may produce this
      effect, which was not seen with xamoterol, because of its specific beta 2
      adrenoceptor partial agonist activity. Elevations in plasma CK produced by this
      type of drug or its withdrawal may cause confusion in the diagnosis of muscle
      disease or myocardial infarction unless the myocardial isoenzyme is measured.

PMID- 1980201
TI  - Sleep laboratory studies on single dose effects of suriclone.
AB  - 1. In a double-blind, placebo-controlled sleep laboratory study single doses of
      suriclone, a new non-benzodiazepine anxiolytic binding to benzodiazepine
      receptors, were investigated with respect to sleep and awakening. 2. Sixteen
      healthy young volunteers spent 10 nights in the sleep laboratory: 1 adaptation
      night, 1 baseline night and 4 drug nights (placebo; 0.2 mg, 0.4 mg suriclone; 2
      mg lorazepam as reference drug) and 4 subsequent wash-out nights (drug-interval:
      1 week). Somnopolygraphic investigations (22.30 h to 06.00 h) were commenced 0.5
      h after drug-intake. A self-rating scale for sleep and awakening quality as well
      as psychometric tests were completed in the morning. 3. Hypnotic effects were
      most pronounced after lorazepam in regard to total sleep time and sleep
      efficiency. After lorazepam as well as after 0.4 mg suriclone nocturnal
      awakenings decreased significantly as compared with placebo, which was reflected
      in an improved subjective sleep quality after both dosages. Suriclone 0.2 mg did
      not induce any alterations in all night sleep. 4. In the morning, well-being,
      drowsiness and reaction time performance deteriorated after lorazepam as compared
      with placebo but not after suriclone. The latter was significantly superior to
      lorazepam with respect to subjective awakening quality, well-being, emotional
      rapport, drowsiness and attention. 5. Blood pressure and pulse remained unchanged
      after all of the drugs. Critical flicker frequency and muscle strength decreased
      only after lorazepam as compared with placebo.

PMID- 1980203
TI  - Development of morphological types and distribution patterns of amacrine cells
      immunoreactive to tyrosine hydroxylase in the cat retina.
AB  - Using an antibody against tyrosine hydroxylase on newborn to 30-day kitten
      retinas, we have been able to follow the development of the dopaminergic amacrine
      cells of the cat retina by light-microscopical investigations of retinal
      wholemounts. The Type 1 or large Toh+ amacrine cells described by others (Oyster
      et al., 1985; Tork & Stone, 1979) and named A18 from a Golgi study (Kolb et al.,
      1981), is at birth (P1) an immature neuron with a small cell body and two or
      three simple thick radiating dendrites stratifying in stratum 1 with many of the
      dendrites ending in enlarged growth cones. With increasing postnatal age, the
      cell body size increases from 12.5 microns diameter to reach 15.5 microns
      diameter at P30. The dendritic fields also increase in size and complexity. At
      P1, cells of the central area exhibit dendritic appendages which then develop
      progressively until at P13 (after eye opening) they are part of rudimentary rings
      and by P30 the dendritic plexus of Toh+ dendrites and rings in stratum 1, typical
      of the adult cells, are complete. Toh+ stained processes with growth cones that
      run deep in stratum 5 of the inner plexiform layer and processes passing to the
      outer plexiform layer first become apparent at P1 in cells of central inferior
      retina but not till after P13 are these processes clearly expressed. At P1, the
      total number of Toh+ Type 1 cells is approximately 4000 and this number remains
      unchanged to the adult retina. However, the retina increases in size over the P1
      P30 stage and thus the mean density of Type 1 Toh+ cells decreases from 30/mm2 at
      P1 to 18/mm2 at P30. The maximum density of Type 1 Toh+ cells occurs in central
      retina 2-4 mm superior temporal to the area centralis, corresponding to the
      maximum rod photoreceptor concentration. A second type of small Toh+ amacrine
      cell can be visualized at P1. This Type 2 cell is characterized by a much smaller
      cell body than Type 1 cells (9 microns diameter), and with faintly stained
      dendrites located in stratum 3 of the inner plexiform layer. During later
      postnatal days, Type 2 cells gradually become unstainable and only few are still
      seen in far peripheral retina by P23. Type 2 Toh+ cells from a total population
      of 40,000 cells at P1 with their highest density occurring in peripheral retina.
      By P13, they cannot be seen in central retina and are reduced to a total
      population of cells staining for the antibody of 7400 cells in far peripheral
      retina.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1980202
TI  - The efficacy of beta-adrenoceptor and calcium-entry blockers in hypertensive
      blacks.
AB  - The data on treatment of hypertension in black patients with beta-adrenoceptor
      blockers (BB) or calcium-entry blockers (CEB) have been reviewed. There is much
      evidence that in monotherapy BB are no better than inert placebo for the majority
      of hypertensive black patients. Their hypotensive action in blacks is less than
      that induced by other antihypertensive agents, mainly diuretics. Comparative
      evaluation of the responsiveness of blacks, whites, and Indians to BB therapy
      showed a poorer control of blood pressure (BP) among blacks than among nonblacks.
      However, when combined with diuretic therapy, BBs are equipotent in blacks and
      whites. The reasons for the hyporesponsiveness of black patients to BB therapy
      are not fully understood. On the other hand, CEBs appear to be as efficacious as
      diuretic therapy in hypertensive blacks. In addition, they lower blood pressure
      to the same extent in black and white patients. They are also proven to be
      effective adjunctive therapy to diuretics for hypertension in blacks. The reason
      for the better responsiveness of blacks to CEB therapy might include the severity
      of hypertension in blacks, their low plasma renin, their blunted sympathetic
      activity, and their high intracellular sodium concentration.

PMID- 1980204
TI  - Glycine stimulates calcium-independent release of 3H-GABA from isolated retinas
      of Xenopus laevis.
AB  - A perfusion system was used to monitor the release of [3H]-GABA from isolated
      retinas of Xenopus laevis. Measurable release was stimulated by glycine at
      concentrations as low as 200 microM. Glycine-stimulated release was blocked by
      strychnine, and was not reduced in "calcium-free" Ringer's solution (0 Ca2+/20 mM
      Mg2+). Glutamate also stimulated calcium-independent release, using
      concentrations as low as 100 microM. In contrast, release stimulated by 25 mM
      potassium was reduced by 80% in calcium-free medium. In most experiments,
      agonists were applied in six consecutive 4-min pulses separated by 10-min washes
      with Ringer's solution. Under these conditions, the release stimulated by 0.5 mM
      glutamate or 25 mM potassium decreased by at least 50% from the first to the
      second pulse, and then gradually decreased with successive applications. In
      contrast, the response to 0.5 mM glycine at first increased and then only
      gradually decreased with successive pulses. These patterns of response to
      different agonists were similar in calcium-free medium. Somatostatin (-14 or -28)
      also stimulated release, and this effect was inhibited by AOAA, an inhibitor of
      GABA degradation. In the presence of AOAA, somatostatin had little effect, except
      at high concentrations of somatostatin (5 microM), which increased both basal and
      glycine-stimulated release. In contrast to somatostatin, glycine-stimulated
      release was much larger in the presence of AOAA. Autoradiography was used to
      investigate which cell types released [3H]-GABA under our conditions.
      Autoradiograms showed that horizontal cells and a population of apparent "off"
      bipolar cells were well-labeled by [3H]-GABA high-affinity uptake. In addition,
      light labeling was seen over numerous amacrine cells. After application of
      glycine, glutamate, or potassium, there was a decrease in label density over
      horizontal cells.

PMID- 1980205
TI  - Quantitative immunogold analysis reveals high glutamate levels in synaptic
      terminals of retino-geniculate, cortico-geniculate, and geniculo-cortical axons
      in the cat.
AB  - A postembedding immunogold procedure was used to estimate quantitatively, at the
      electron-microscopical level, the intensity of glutamate (GLU) immunoreactivity
      in different identifiable profiles of the lateral geniculate nucleus (LGN) and
      perigeniculate nucleus (PGN) of the cat. Synaptic terminals of retinal and
      cortical origins in the LGN, and of axon collaterals of geniculo-cortical relay
      cells in the PGN, were identified by previously determined ultrastructural
      features. Processes of interneurons or relay cells were identified by being
      immunoreactive or non-immunoreactive, respectively, in serial thin section
      reacted with a GABA antibody. The results showed that synaptic terminals of
      geniculo-cortical relay cells in the PGN have significantly higher levels of GLU
      immunoreactivity than their parent somata or dendrites in the LGN; this suggests
      transmitter storage of this amino acid in these terminals. By contrast, synaptic
      terminals of interneurons did not show enrichment of GLU relative to their parent
      somata. This argues against the possibility that the relative enrichment of GLU
      in relay cells terminals is due to factors other than presynaptic storage. In
      addition, axon collateral terminals of relay cells in the pGN, as well as retinal
      and cortical terminals in the LGN, showed significantly higher GLU
      immunoreactivity than GABAergic terminals. These immunocytochemical results
      suggest that GLU is a neurotransmitter in the retino-geniculate, cortico
      geniculate, and geniculo-cortical pathways in the cat.

PMID- 1980206
TI  - Changes in the properties of the thyrotropin receptor antibody in patients with
      Graves' disease after radioiodine treatment.
AB  - We investigated the effect of a single dose of 131I upon thyrotropin receptor
      antibodies (TRAb) in 21 patients with Graves' disease. The thyrotropin receptor
      antibodies were assessed by parallel measurements of thyrotropin binding
      inhibitor immunoglobulin (TBII), thyroid stimulating antibody (TSAb) and thyroid
      stimulation blocking antibody (TSBAb) in serum by radoreceptor assay, stimulation
      of adenlate cyclase and inhibition of TSH-stimulated adenylate cyclase activation
      in FRTL-5 cells, respectively. Prior to radioiodine treatment, TBII was detected
      in all 21 patients and TSAb in 19 patients. After radioiodine treatment, TBII
      activities did not change during the 12-months observation period, but in eight
      patients TSAb activities gradually decreased and were undetectable at the end of
      the 12-month observation period. Persistence of TSAb was not associated with the
      clinical outcome. Eight patients developed hypothyroidism within one year after
      radioiodine treatment. Three of the hypothyroid patients developed TSBAb, and the
      appearance of TSBAb coincided with the development of hypothyroidism. These
      results suggest that TSBAb might develop after radioiodine treatment in a
      minority of patients with Graves' disease and that the appearance of TSBAb, in
      addition to radiation-induced thyroid destruction, might be involved in the
      development of hypothyroidism following radioiodine treatment.

PMID- 1980207
TI  - Contribution of histidine residues to the conformational stability of
      ribonuclease T1 and mutant Glu-58----Ala.
AB  - The pK values of the histidine residues in ribonuclease T1 (RNase T1) are
      unusually high: 7.8 (His-92), 7.9 (His-40), and 7.3 (His-27) [Inagaki et al.
      (1981) J. Biochem. 89, 1185-1195]. In the RNase T1 mutant Glu-58----Ala, the
      first two pK values are reduced to 7.4 (His-92) and 7.1 (His-40). These lower pKs
      were expected since His-92 (5.5 A) and His-40 (3.7 A) are in close proximity to
      Glu-58 at the active site. The conformational stability of RNase T1 increases by
      over 4 kcal/mol between pH 9 and 5, and this can be entirely accounted for by the
      greater affinity for protons by the His residues in the folded protein (average
      pK = 7.6) than in the unfolded protein (pk approximately 6.6). Thus, almost half
      of the net conformational stability of RNase T1 results from a difference between
      the pK values of the histidine residues in the folded and unfolded conformations.
      In the Glu-58----Ala mutant, the increase in stability between pH 9 and 5 is
      halved (approximately 2 kcal/mol), as expected on the basis of the lower pK
      values for the His residues in the folded protein (average pK = 7.1). As a
      consequence, RNase T1 is more stable than the mutant below pH 7.5, and less
      stable above pH 7.5. These results emphasize the importance of measuring the
      conformational stability as a function of pH when comparing proteins differing in
      structure.

PMID- 1980208
TI  - Active-site mutations of diphtheria toxin: effects of replacing glutamic acid-148
      with aspartic acid, glutamine, or serine.
AB  - Glutamic acid-148, an active-site residue of diphtheria toxin identified by
      photoaffinity labeling with NAD, was replaced with aspartic acid, glutamine, or
      serine by directed mutagenesis of the F2 fragment of the toxin gene. Wild-type
      and mutant F2 proteins were synthesized in Escherichia coli, and the
      corresponding enzymic fragment A moieties (DTA) were derived, purified, and
      characterized. The Glu----Asp (E148D), Glu----Gln (E148Q), and Glu----Ser (E148S)
      mutations caused reductions in NAD:EF-2 ADP-ribosyltransferase activity of ca.
      100-, 250-, and 300-fold, respectively, while causing only minimal changes in
      substrate affinity. The effects of the mutations on NAD-glycohydrolase activity
      were considerably different; only a 10-fold reduction in activity was observed
      for E148S, and the E148D and E148Q mutants actually exhibited a small but
      reproducible increase in NAD-glycohydrolytic activity. Photolabeling by
      nicotinamide-radiolabeled NAD was diminished ca. 8-fold in the E148D mutant and
      was undetectable in the other mutants. The results confirm that Glu-148 plays a
      crucial role in the ADP-ribosylation of EF-2 and imply an important function for
      the side-chain carboxyl group in catalysis. The carboxyl group is also important
      for photochemical labeling by NAD but not for NAD-glycohydrolase activity. The pH
      dependence of the catalytic parameters for the ADP-ribosyltransferase reaction
      revealed a group in DTA-wt that titrates with an apparent pKa of 6.2-6.3 and is
      in the protonated state in the rate-determining step.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1980209
TI  - Identification of glycoinositol phospholipid linked and truncated forms of the
      scrapie prion protein.
AB  - Analysis of carboxy-terminal peptides derived from endoproteinase Lys-C digests
      of the scrapie isoform of the hamster prion protein revealed that the majority of
      the molecules are glycoinositol phospholipid linked through ethanolamine attached
      at serin-231. However, approximately 15% of PrPSc had a carboxy-terminal peptide
      that ends at glycine-228. It is intriguing that this glycine is part of the PrP
      sequence Gly-Arg-Arg, which is an established target sequence for the proteolysis
      and release of bioactive peptides from larger precursors. The mechanism of
      formation, as well as the role of the truncated carboxy terminus in the
      dissemination and neuropathology of scrapie, remains to be determined.

PMID- 1980210
TI  - Direct evidence for GTP and GDP-Pi intermediates in microtubule assembly.
AB  - Identification of the kinetic intermediates in GTP hydrolysis on microtubules and
      characterization of their assembly properties is essential in understanding
      microtubule dynamics. By using an improved glass filter assay that selectively
      traps microtubules with a dead time of 2 s and monitoring taxol-induced rapid
      assembly of microtubules from [gamma-32P,3H]GTP-tubulin 1:1 complex, direct
      evidence has been obtained for GTP- and GDP-Pi-microtubule transient states in
      the early stages of the polymerization process. A simple kinetic analysis of GTP
      hydrolysis on microtubules within two sequential pseudo-first-order processes led
      to apparent first-order rate constants of 0.065 s-1 for the cleavage of the gamma
      phosphate and 0.02 s-1 for the liberation of Pi, assuming a simple random model.
      Apparent rate constants for GTP hydrolysis and Pi release were independent of the
      composition of the buffer used to polymerize tubulin. The significance of these
      values with respect to those derived from previous studies from this and other
      laboratories and the possibility of a vectorial model for GTP hydrolysis are
      discussed.

PMID- 1980211
TI  - Histidine-40 of ribonuclease T1 acts as base catalyst when the true catalytic
      base, glutamic acid-58, is replaced by alanine.
AB  - Mechanisms for the ribonuclease T1 (RNase T1; EC 3.1.27.3) catalyzed
      transesterification reaction generally include the proposal that Glu58 and His92
      provide general base and general acid assistance, respectively [Heinemann, U., &
      Saenger, W. (1982) Nature (London) 299, 27-31]. This view was recently challenged
      by the observation that mutants substituted at position 58 retain high residual
      activity; a revised mechanism was proposed in which His40, and not Glu58, is
      engaged in catalysis as general base [Nishikawa, S., Morioka, H., Kim, H.,
      Fuchimura, K., Tanaka, T., Uesugi, S., Hakoshima, T., Tomita, K., Ohtsuka, E., &
      Ikehara, M. (1987) Biochemistry 26, 8620-8624]. To clarify the functional roles
      of His40, Glu58, and His92, we analyzed the consequences of several amino acid
      substitutions (His40Ala, His40Lys, His40Asp, Glu58Ala, Glu58Gln, and His92Gln) on
      the kinetics of GpC transesterification. The dominant effect of all mutations is
      on Kcat, implicating His40, Glu58, and His92 in catalysis rather than in
      substrate binding. Plots of log (Kcat/Km) vs pH for wild-type, His40Lys, and
      Glu58Ala RNase T1, together with the NMR-determined pKa values of the histidines
      of these enzymes, strongly support the view that Glu58-His92 acts as the base
      acid couple. The curves also show that His40 is required in its protonated form
      for optimal activity of wild-type enzyme. We propose that the charged His40
      participates in electrostatic stabilization of the transition state; the
      magnitude of the catalytic defect (a factor of 2000) from the His40 to Ala
      replacement suggests that electrostatic catalysis contributes considerably to the
      overall rate acceleration. For Glu58Ala RNase T1, the pH dependence of the
      catalytic parameters suggests an altered mechanism in which His40 and His92 act
      as base and acid catalyst, respectively. The ability of His40 to adopt the
      function of general base must account for the significant activity remaining in
      Glu58-mutated enzymes.

PMID- 1980212
TI  - Determinants of visual pigment absorbance: identification of the retinylidene
      Schiff's base counterion in bovine rhodopsin.
AB  - The role of negatively charged residues in tuning the absorbance spectrum of
      bovine rhodopsin has been tested by mutating each aspartate and glutamate to
      asparagine and glutamine, respectively. Previous work demonstrated that
      aspartate83, glutamate122, and glutamate134 can be replaced by neutral residues
      with little or no effect on the absorbance spectrum of the resulting pigment
      [Nathans, J. (1990) Biochemistry 29, 937-942]. With one exception, mutations at
      the remaining 19 aspartate and glutamate residues result in very nearly wild-type
      absorbance spectra. The exception is glutamate113: mutation to glutamine causes
      the pigment to absorb at 380 nm, reflecting deprotonation of the retinylidene
      Schiff's base. Upon addition of either chloride, bromide, or iodide, the
      absorbance rapidly shifts to 495, 498, or 504.5 nm, respectively, reflecting
      protonation of the Schiff's base. The progressive red shift observed upon
      addition of halides with larger atomic radii strongly suggests that halides are
      serving as the Schiff's base counterion. Halides have no effect on the absorbance
      spectrum of wild-type rhodopsin. I infer, therefore, that glutamate113 is the
      retinylidene Schiff's base counterion in wild-type rhodopsin. Sakmar et al.
      [(1989) Proc. Natl. Acad. Sci. U.S.A. 86, 8309-8313] and Zhukovsky and Oprian
      [(1989) Science 246, 928-930] have arrived at the same conclusion based upon a
      related series of experiments. These data support a model in which spectral
      tuning in bovine rhodopsin results from interactions between the polyene chain of
      11-cis-retinal and uncharged amino acids in the binding pocket.

PMID- 1980213
TI  - Escherichia coli maltodextrin phosphorylase: contribution of active site residues
      glutamate-637 and tyrosine-538 to the phosphorolytic cleavage of alpha-glucans.
AB  - The role of Escherichia coli maltodextrin phosphorylase (EC 2.4.1.1) active site
      residues Glu637 and Tyr538 which line the sugar-phosphate contact region of the
      enzyme was investigated by site-directed mutagenesis. Substitution of Glu637 by
      an Asp or Gln residue reduced kcat to approximately 0.2% of wild-type activity,
      while the Km values were affected to a minor extent. This indicated participation
      of Glu637 in transition-state binding rather than in ground-state binding. 31P
      NMR analysis of the ionization state of enzyme-bound pyridoxal phosphate
      suggested that Glu637 is also involved in modulation of the protonation state of
      the coenzyme phosphate observed during catalysis. Despite loss of proposed
      hydrogen-bonded substrate contacts, the Tyr538Phe mutant enzyme retained more
      than 10% activity; the apparent affinity of all substrates was slightly
      decreased. Mutations at either site affected the error rate of the enzyme (ratio
      of hydrolysis/phosphorolysis). Besides a role in substrate binding, the hydrogen
      bond network of Tyr538 supports the exclusion of water from the active site.

PMID- 1980214
TI  - The p220 component of eukaryotic initiation factor 4F is a substrate for multiple
      calcium-dependent enzymes.
AB  - Eukaryotic initiation factor 4F (eIF-4F) is a multisubunit protein that functions
      in the first step of the binding of capped mRNAs to the small ribosomal subunit.
      Its largest polypeptide component, p220, is cleaved following poliovirus
      infection. This is thought to inactivate eIF-4F function, thereby preventing cap
      dependent initiation of translation of cellular mRNAs. In this report, we show
      that p220 in extracts of uninfected HeLa cells is specifically lost in the
      presence of calcium. The responsible activities have been partially purified and
      identified as the calcium-dependent, neutral, cysteine proteases calpains I and
      II. In addition, a third calcium-dependent activity was resolved from the
      calpains and also results in the loss of p220. This activity has properties
      similar to a transglutaminase and copurifies with tissue transglutaminase through
      several chromatographic steps. None of these calcium-dependent activities appears
      to mediate p220 cleavage in poliovirus-infected cells.

PMID- 1980215
TI  - A new form of guanylyl cyclase is preferentially expressed in rat kidney.
AB  - On the basis of the conserved amino acid sequences of the catalytic domain of
      both soluble and plasma membrane forms of guanylyl cyclase, we have used the
      polymerase chain reaction to identify a new form of guanylyl cyclase that is
      expressed principally in kidney. The cDNA for this new form (GC-S beta 2) codes
      for a 76.3-kDa protein, which most closely resembles a 70-kDa subunit (GC-S beta
      1) of the lung soluble guanylyl cyclase. The mRNA for GC-S beta 1 is
      preferentially expressed in lung and brain, whereas GC-S beta 2 mRNA is more
      abundant in kidney and liver. An 86 amino acid carboxyl-terminal region extends
      beyond the C-terminus of GC-S beta 1 and contains a consensus sequence (-C-V-V-L)
      for isoprenylation/carboxymethylation. This is the first demonstration of
      heterogeneity among the heterodimeric forms of guanylyl cyclase and suggests
      differential regulation.

PMID- 1980216
TI  - Heterodimerization of the erbB-1 and erbB-2 receptors in human breast carcinoma
      cells: a mechanism for receptor transregulation.
AB  - The erbB-1 and erbB-2 protooncogenes encode homologous membrane receptors that
      respectively bind epidermal growth factor (EGF) and a still incompletely
      characterized ligand. Binding of EGF to its receptor is known to increase
      tyrosine phosphorylation of the erbB-2/neu receptor in tumor cells. To
      investigate the mechanism of this transregulatory pathway, we analyzed the
      interactions between the two receptors in SKBR-3 human breast carcinoma cells.
      Chemical cross-linking of 125I-labeled EGF revealed that the radiolabeled EGF
      receptor coimmunoprecipitates with the erbB-2/neu receptor. In addition a cross
      linked species of 360-kdalton molecular mass is also coimmunoprecipitated. The
      formation of the latter species is absolutely dependent on the presence of EGF
      receptor and thus appears to represent a heterodimer of the erbB-1 and erbB-2
      receptors. In vitro kinase reaction assays revealed that receptor
      heterodimerization is induced by EGF binding and leads to a dramatic increase in
      the self-phosphorylation capacity of the dimerized receptors. Moreover, analysis
      of living SKBR-3 cells suggested that most of the EGF-induced transregulation of
      the erbB-2/neu receptor is due to receptor heterodimerization. In conclusion,
      heterodimers of erbB-1 and erbB-2 receptors may provide a mechanism for dual
      transductory functions of growth factors of breast tumor cells.

PMID- 1980217
TI  - Counterflow of L-glutamate in plasma membrane vesicles and reconstituted
      preparations from rat brain.
AB  - Membrane vesicles from rat brain exhibit sodium-dependent uptake of L
      [3H]glutamate in the absence of any transmembrane ion gradients. The substrate
      specificity of the process is identical with (Na+ + K+)-coupled L-glutamate
      accumulation. Although these vesicles are prepared after osmotic shock and are
      washed repeatedly, they contain about 1.5 nmol/mg of protein endogenous L
      glutamate, apparently located inside the vesicles. The affinity of the process
      (Km approximately 1 microM) is similar to that of (Na+ + K+)-dependent
      accumulation by the L-glutamate transporter. Membrane vesicles have been
      disrupted by the detergent cholate, and the solubilized proteins have been
      subsequently reconstituted into liposomes. The reconstituted proteoliposomes also
      exhibit the above uptake--with the same characteristics--provided they contain
      entrapped cold L-glutamate. Counterflow is optimal when sodium is present on both
      sides of the membrane, but partial activity is still observed when sodium is
      present either on the inside or on the outside. Increasing the L-glutamate
      concentration above the Km results in counterflow completely independent of cis
      sodium. The initial rate of counterflow is 100-200-fold lower than that of net
      trans potassium dependent flux. The rate of net flux in the presence of trans
      sodium or lithium is about 10-fold lower than when choline or Tris are used
      instead. However, the rate of counterflow (no internal potassium present) was not
      stimulated by replacing internal sodium or lithium by internal choline.
      Therefore, optimal functioning of the transporter requires internal potassium
      while internal sodium and lithium are inhibitory.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1980218
TI  - Diagnostic utility of flumazenil in coma with suspected poisoning: a double
      blind, randomised controlled study.
AB  - OBJECTIVE: To assess the diagnostic value and safety of the benzodiazepine
      antagonist flumazenil in patients with coma of unclear origin with suspected
      poisoning. DESIGN: Double blind, placebo controlled, randomised study. SETTING:
      Intensive care unit at a major teaching hospital. PATIENTS: 105 Unconscious
      adults admitted consecutively with suspected drug overdosage during 18 months
      from a total of 362 cases of poisoning. Exclusion criteria were pregnancy,
      epilepsy, obvious poisoning with drugs identified unequivocally from information
      from relatives or others as other than benzodiazepines, and coma score greater
      than 10 on a scale graded from 4 to 20. Patients were allocated randomly to
      receive flumazenil (21 men and 32 women) or placebo (25 men and 27 women).
      INTERVENTIONS: Intravenous injection of flumazenil (10 ml, 0.1 mg/ml) or placebo
      (10 ml vehicle alone) given double blind over three minutes. MAIN OUTCOME
      MEASURES: Serum and urine concentrations of benzodiazepines, antidepressants, and
      several other agents; blood gas tensions; standardised evaluation on admission
      and five minutes after the injection by means of coma scale score and urgent
      diagnostic or therapeutic interventions indicated according to the history and
      clinical examination; standardised interview after the injection to try to
      ascertain further information; and adverse reactions. RESULTS: Benzodiazepines
      were found in the serum in 36 of the 53 patients in the flumazenil group and in
      37 of the 52 who received placebo. The average coma scale score increased
      significantly after injection in the flumazenil group (6.4 v 12.1, p less than
      0.001) but not in the placebo group. In the flumazenil group several
      interventions were rendered unnecessary by the injection: gastric lavage and
      urinary catheterisation (19 patients each), intubation (21), artificial
      ventilation and computed tomography of the brain (three patients each), blood
      culture and lumbar puncture (one patient each), and electroencephalography (two).
      In the placebo group the indications for these procedures did not change in any
      patient after injection. The 95% confidence interval for the difference in
      reduction of the frequency of indications for gastric lavage after injection
      between the two groups was 21% to 51%, that for intubation 25% to 55%, and that
      for urinary catheterisation 21% to 51%. In the flumazenil group 21 patients gave
      valuable information on their drug ingestion within 10 minutes after injection
      compared with only one in the placebo group (p less than 0.001). Nine adverse
      reactions were recorded in the flumazenil group, eight of which were graded as
      mild and one severe. The safety of the antagonist was acceptable, even though 60%
      of the patients in the flumazenil group had multiple drug poisoning including
      benzodiazepine. No epileptic seizures or arrhythmias were recorded. CONCLUSION:
      Flumazenil is a valuable and safe differential diagnostic tool in unclear cases
      of multiple drug poisoning.

PMID- 1980219
TI  - Progression of HIV infection in misusers of injected drugs who stop injecting or
      follow a programme of maintenance treatment with methadone.
AB  - OBJECTIVE: To see whether misusers of injected drugs who stop injecting or switch
      to a programme of maintenance treatment with methadone have a reduced risk of
      progression of HIV infection when compared with a group of persistent misusers.
      DESIGN: Observational cohort study in HIV seropositive subjects with a current or
      past history of misusing injected drugs. SETTING: HIV outpatient clinic at the
      University Hospital of Zurich, Switzerland. PATIENTS: 297 Current and former
      parenteral drug misusers (median age 27) with asymptomatic HIV infection. During
      the observation period 80 subjects adhered to a programme of maintenance
      treatment with methadone, 124 continued with parenteral drug misuse, and 93
      former misusers remained free of illicit drugs. No antiretroviral treatment was
      given during the study. MAIN OUTCOME MEASURES: Probability of progression of HIV
      infection from asymptomatic to symptomatic (Centers for Disease Control stage IV)
      as calculated by life table analysis and compared in the three groups of patients
      by means of a log rank test, and predictors of disease progression as analysed
      with a Cox proportional hazards regression model. RESULTS: The 297 patients were
      followed up for a median of 16 months. The median duration of injecting drug
      misuse before enrollment was 7.1 years. There were no significant differences
      among the three groups with respect to CD4+ counts at the beginning of the study
      (median 0.44 x 10(9)/l). Life table analysis showed a significantly lower
      probability of progression of HIV disease in both the methadone treated group and
      former drug misusers than in persistent injecting drug misusers. Multivariate
      regression analysis showed a relative risk of progression of the disease of 1.78
      (95% confidence interval 1.20 to 2.67; p less than 0.01) in persistent injecting
      drug misusers, 0.48 (0.29 to 0.77; p less than 0.01) in the methadone treated
      group, and 0.66 (0.41 to 1.06; p = 0.085) in former drug misusers. CONCLUSIONS:
      Stopping the misuse of injected drugs slows the progression of HIV disease in
      infected subjects. Drug treatment programmes are effective in secondary
      prevention of HIV associated morbidity.

PMID- 1980221
TI  - Letter from Brasilia. Yellow fever.

PMID- 1980220
TI  - Salmeterol in nocturnal asthma: a double blind, placebo controlled trial of a
      long acting inhaled beta 2 agonist.
AB  - OBJECTIVE: To determine whether inhaled salmeterol, a new long acting inhaled
      beta adrenergic agonist, reduces nocturnal bronchoconstriction and improves sleep
      quality in patients with nocturnal asthma. DESIGN: Randomised, double blind,
      placebo controlled crossover study. SETTING: Hospital outpatient clinics in
      Edinburgh. SUBJECTS: Twenty clinically stable patients (13 women, seven men) with
      nocturnal asthma, median age 39 (range 18-60) years. INTERVENTIONS: Salmeterol 50
      micrograms and 100 micrograms and placebo taken each morning and evening by
      metered dose inhaler. Rescue salbutamol inhalers were provided throughout the run
      in and study periods. MAIN OUTCOME MEASURES: Improvement in nocturnal asthma as
      measured by peak expiratory flow rates and change in sleep quality as measured by
      electroencephalography. RESULTS: Salmeterol improved the lowest overnight peak
      flow rate at both 50 micrograms (difference in median values (95% confidence
      interval for difference in medians) 69 (18 to 88) l/min) and 100 micrograms (72
      (23 to 61) l/min) doses twice daily. While taking salmeterol 50 micrograms twice
      daily patients had an objective improvement in sleep quality, spending less time
      awake or in light sleep (-9 (-4 to -44) min) and more time in stage 4 sleep (26
      (6-34) min). CONCLUSIONS: Salmeterol is an effective long acting inhaled
      bronchodilator for patients with nocturnal asthma and at a dose of 50 micrograms
      twice daily improves objective sleep quality.

PMID- 1980222
TI  - HIV infection in the Edinburgh haemophiliac cohort.

PMID- 1980223
TI  - Histochemical strategies in the study of neural evolution.
AB  - The use of histochemical methods, including enzyme histochemical,
      immunohistochemical and pathway tracing methods, as tools for testing hypotheses
      about the mechanism of neural evolution is reviewed. Many hypotheses have been
      proposed to explain aspects of neural evolution, including the occurrence of
      encephalization, quantitative changes in homologous cell populations, changes in
      the alignment, orientation and parcellation of neuronal populations into
      cytoarchitectonic units, and the appearance of new neuronal phenotypes. It is
      argued here that neural evolution must be viewed as a set of coordinated changes
      in neural circuits, rather than as a set of discrete events. For illustrative
      purposes the present discussion focuses on the use of histochemical methods in
      testings hypotheses about neural evolution in the basal ganglia system of
      amniotes. Three problem areas are considered: the bases for (1) differences in
      the alignment and organization of catecholaminergic and noncatecholaminergic
      neurons into cytoarchitectonic fields within the substantia nigra; (2)
      differences in the relative size and neurotransmitter organization of the caudal
      nigral cell groups and (3) differences in the organization of pallidal efferent
      systems, including the organization of pallidal-pretectal and pallidal-thalamic
      projection systems. Furthermore, the role of comparative data in framing
      hypotheses concerning the adaptive significance of such changes is also
      considered.

PMID- 1980224
TI  - Cyclic AMP-induced shape changes of astrocytes are accompanied by rapid
      depolymerization of actin.
AB  - Agents that increase intracellular cyclic AMP produce a process-bearing
      morphology in astrocytes. We have examined short-term re-arrangements of the
      astrocyte cytoskeleton during this shape conversion. Primary cultures of
      astrocytes from neonatal rat forebrain were grown at low density as polygonal
      shaped cells. Treatment with 1 mM dibutyryl cAMP in the absence of serum produced
      rapid changes in cell shape (100% of cells as flat to 90% showing cytoplasmic
      contraction and processes in 60 min). In the presence of serum, similar changes
      took place, but more slowly. No changes in total cellular levels of GFAP,
      vimentin, tubulin or actin were observed over a 2-h period of treatment. There
      was a shift in actin from a Triton X-100-insoluble pool to a soluble pool, with a
      40% reduction in insoluble actin. The kinetics of this shift paralleled kinetics
      of shape change. The shift also corresponded to a loss of stress fibers,
      visualized with rhodamine-phalloidin. Intermediate stages of stress fiber loss
      were observed as short, wavy or small ring profiles. Colchicine prevented the
      dBcAMP-induced changes in shape. If cells were first treated with taxol, however,
      subsequent exposure to colchicine did not inhibit contraction. Thus, dBcAMP,
      presumably through a cAMP-dependent kinase, depolymerizes actin in stress fiber
      form as cells contract. In addition, an intact microtubule system may be required
      for the changes in shape. Treatment with dBcAMP also caused the disappearance of
      vinculin-containing attachment sites, indicating that adhesion plaques, or at
      least the association of vinculin with them, are lost during the time of
      microfilament bundle dissociation.

PMID- 1980225
TI  - Most somatostatin-immunoreactive neurons in the rat fascia dentata do not contain
      the calcium-binding protein parvalbumin.
AB  - A selective loss of somatostatin (SS)-containing neurons in the hilar region has
      been reported in patients suffering from temporal lobe epilepsy. Conversely,
      neurons containing calcium-binding proteins such as parvalbumin (PARV) are known
      to be very resistant under experimental seizure conditions. In this study, we
      analyzed the coexistence of SS and PARV in neurons of the rat fascia dentata by
      using serial semi-thin cryostat sections for pre-embedding immunocytochemistry.
      Our results show that only 5.7% of the SS-immunoreactive hilar neurons contain
      PARV. The data suggest that SS-containing hilar neurons are less protected
      against seizure-induced calcium overload than other neurons containing calcium
      binding proteins.

PMID- 1980226
TI  - Carnosine-, calcitonin gene-related peptide- and tyrosine hydroxylase
      immunoreactivity in the mouse olfactory bulb following peripheral denervation.
AB  - We report the effects of olfactory peripheral deafferentation by intranasal
      irrigation with ZnSO4 on carnosine and CGRP immunoreactivities in the mouse
      olfactory system. In the normal rodent olfactory epithelium carnosine
      immunoreactivity is associated with the olfactory receptor neurons. Conversely,
      CGRP immunoreactivity appears to be associated with the trigeminal innervation of
      the nasal cavity. Following lesion the magnitude of carnosine immunoreactivity in
      the olfactory epithelium is strongly reduced while CGRP immunoreactivity is
      unaffected. In the olfactory bulb, deafferentation causes a strong reduction of
      carnosine immunoreactivity in the glomerular layer and, concurrently, of TH
      immunoreactivity in the juxtaglomerular neurons. CGRP immunoreactive fibers in
      the olfactory bulb are abundant in the glomerular layer both before and after
      deafferentation. These data demonstrate that, in the adult mouse, the
      immunocytochemically detectable levels of CGRP are not altered following lesion
      and indicate CGRP is not released directly from the olfactory neurons to induce
      TH production.

PMID- 1980228
TI  - Antagonism of stimulation-produced antinociception from ventrolateral pontine
      sites by intrathecal administration of alpha-adrenergic antagonists and naloxone.
AB  - Focal electrical stimulation of the ventrolateral pontine tegmentum in conscious
      rats induced antinociception in approximately one-half of the animals screened,
      as indicated by a marked suppression of the thermally evoked tail-flick flexion
      reflex. The effectiveness of ventrolateral pontine stimulation in elevating tail
      flick latency was significantly reduced by intrathecal microinjection of 30
      micrograms of the non-selective alpha-adrenergic antagonist phentolamine, and was
      largely abolished by a 60-micrograms dose of this drug. The blockade of
      ventrolateral pontine stimulation-produced antinociception by phentolamine was
      maximal by 15 min postinjection, and was still evident 60 min after drug
      microinjection. Ventrolateral pontine stimulation-produced antinociception was
      also attenuated by intrathecal administration of the alpha 2-selective antagonist
      yohimbine (37 micrograms) and the opioid antagonist naloxone (30 micrograms), but
      not the alpha 1 antagonist WB-4101 (37 micrograms), the beta-adrenergic
      antagonist propranolol (111.6 micrograms) nor the serotonergic antagonist
      methysergide (30 micrograms). However, the antagonism of pontine stimulation
      produced antinociception by naloxone was unlike that of phentolamine and
      yohimbine, in that it developed slowly and was only evident at 60 min
      postinjection. Hence naloxone's site of action may be distant from the injection
      site. These data indicate that the thermal antinociception produced by
      stimulation of the ventrolateral pons is mediated through spinal alpha 2
      receptors and opioid receptors of uncertain location. The close proximity of many
      of the effective electrode placements to the rostral A5 and ventral subcoerulear
      A7 noradrenergic cell groups suggests that noradrenergic spinopetal projections
      arising from these groups are involved in mediating the antinociception induced
      by stimulating these sites.

PMID- 1980227
TI  - Synaptic effects of intraspinal stretch receptor neurons mediating movement
      related feedback during locomotion.
AB  - The flattened lamprey spinal cord contains stretch-sensitive edge cells located
      along the lateral margin, with dendritic processes sensing the lateral bending of
      the cord during each swim cycle. These intraspinal stretch receptor neurons
      provide movement-related sensory feedback input to the generator network for
      locomotion causing a powerful entrainment of the rhythm. In order to elucidate
      the synaptic effects of edge cells we have performed paired intracellular
      recordings and staining with Lucifer yellow. Monosynaptic connections that may
      explain entrainment were found to locomotor central pattern generator
      interneurons. Edge cells with an ipsilateral axon elicited excitatory
      postsynaptic potentials (EPSPs) in ipsilateral interneurons. In addition, such
      edge cells evoked kainate/quisqualate receptor mediated EPSPs in ipsilateral
      motoneurons. This pathway mediates an intraspinal stretch reflex analogous to the
      muscle spindle mediated stretch reflex of mammals. Edge cells with a
      contralateral axon produced monosynaptic glycinergic IPSPs in contralateral
      neurons, including contralateral edge cells.

PMID- 1980229
TI  - Stereospecific transport of Tyr-MIF-1 across the blood-brain barrier by peptide
      transport system-1.
AB  - Previous studies have suggested that peptide transport system-1 (PTS-1), the
      saturable system that transports Tyr-MIF-1, the enkephalins, and related peptides
      out of the central nervous system (CNS), exhibits stereospecificity. In the
      present studies, we showed that 125I-L-Tyr-MIF-1, but not 131I-D-Tyr-MIF-1, was
      cleared from the CNS more rapidly than could be accounted for by nonspecific
      mechanisms. Such clearance was inhibited by a 1.0 nmol dose of L-Tyr-MIF-1, but
      not by D-Tyr-MIF-1. Neither L- nor D-Tyr-MIF-1 altered the much lower clearance
      of I-D-Tyr-MIF-1 from the brain. Radioactivity recovered from the vascular space
      after the injection of 125I-Tyr-MIF-1 into the lateral ventricle of the brain
      eluted by HPLC primarily as intact peptide, demonstrating that most of the Tyr
      MIF-1 was not degraded during transport. By contrast, the nonsaturable
      unidirectional influx of Tyr-MIF-1 into the CNS did not distinguish between the
      isomers. These studies confirm and extend the observations that Tyr-MIF-1 is
      transported out of the CNS by a saturable, stereospecific transport system as an
      intact peptide while the influx into the CNS is by a nonsaturable mechanism that
      does not distinguish between the isomers.

PMID- 1980230
TI  - Microdialysis in the posterior hypothalamus: sodium chloride affects
      norepinephrine release, mean arterial pressure, heart rate and behavior in awake
      rats.
AB  - A microdialysis probe, implanted in the posterior hypothalamus (PH) was used to
      examine changes of extracellular norepinephrine (NE) in freely moving rats from
      which mean arterial pressure (mAP) and heart rate (HR) were continuously
      monitored. Artificial cerebrospinal fluid (aCSF) was pumped through the probe and
      10-microliters dialysate samples were collected at 5-minute intervals and
      analyzed for NE by radioenzymatic assay. High sodium chloride (NaCl)-aCSF
      solution elicited pressor and tachycardiac responses and locomotor activity
      coupled with significant increases in levels of dialysate NE. The latter and the
      associated cardiovascular effects were significantly attenuated by perfusate
      lidocaine (0.5%). When alpha-adrenergic receptors in PH were blocked by
      phenoxybenzamine (0.165 M), high NaCl-aCSF released NE but the associated
      cardiovascular effects were attenuated. In addition, intravenous ganglionic
      blockade with hexamethonium (25 mg/kg) also attenuated cardiovascular responses
      during the high NaCl-aCSF perfusion of PH. These results indicate that PH is one
      of the important areas for central actions of NaCl and that the cardiovascular
      and locomotor responses produced by central NaCl, in part, depend on
      neuroadrenergic activity in PH.

PMID- 1980232
TI  - Proceedings of the Second International Symposium on Improvement of Antitumor
      Drug Therapeutic Index by Toxicity Reduction. Heidelberg, 6-7 November 1989.

PMID- 1980231
TI  - Effects of cocaine on tyrosine hydroxylase activity in brain areas from SHR and
      WKY.
AB  - Basal tyrosine hydroxylase activity was the same in the nuclei accumbens and
      hypothalami of WKY and SHR. Basal striatal enzyme activity was lower in SHR than
      in WKY. Acute and subacute cocaine administration altered enzyme activity only in
      striata and nuclei accumbens of WKY. The central dopaminergic system of SHR
      appears to be less active and less sensitive to cocaine than that of WKY.

PMID- 1980233
TI  - Modulation of antitumour drug resistance: experimental laboratory data and
      results of clinical evaluation.
AB  - Laboratory studies have provided a number of interesting leads relating to
      modulation of antitumour drug resistance. Several ideas have been evaluated
      clinically and phase I studies with certain newer agents are planned.

PMID- 1980234
TI  - Cyclic GMP regulates free cytosolic calcium in the pancreatic acinar cell.
AB  - The present studies were performed in order to measure the effects of cyclic GMP
      (cGMP) on the regulation of free cytosolic calcium [( Ca2+]i) in the pancreatic
      acinar cell. In guinea pig dispersed pancreatic acini the findings demonstrated
      that the Ca2+ ionophore, Br A23187, caused a sustained increase in [Ca2+]i in the
      presence of 3 mM CaCl2 in the media and a transient 20 fold rise in cellular cGMP
      followed by a sustained 3-4 fold rise in cellular cGMP. Increasing cellular cGMP
      with nitroprusside, hydroxylamine or dibutyryl cGMP had no effect on resting
      [Ca2+]i. However, these agents attenuated the increase in [Ca2+]i resulting from
      Br A23187-induced Ca2+ influx. Nitroprusside also attenuated the carbachol
      induced sustained rise in [Ca2+]i that resulted from Ca2+ influx. The
      nitroprusside effect on carbachol-stimulated acini occurred without decreasing
      Ca2+ influx across the plasma membrane or alteration in the mobilization of Ca2+
      from the intracellular agonist-sensitive pool. Inhibition of the increase in
      cellular cGMP caused by Br A23187 by the guanylate cyclase inhibitor, 6-anilino
      5,8-quinolinedione (LY83583), resulted in augmentation of the increase in
      [Ca2+]i. This augmentation was reversed with dibutyryl cGMP. These results
      indicated that cGMP regulated [Ca2+]i in the pancreatic acinar cell. The
      mechanism involves the removal of Ca2+ from the cytoplasm.

PMID- 1980235
TI  - Effects of the alpha 2-adrenoceptor agonist UK14304 on pressor responses in
      pithed rats.
AB  - 1. Intravenous infusions of UK14304 (0.3-10 micrograms/kg per min) in pithed rat
      produced dose-dependent pressor responses which were not affected by prazosin (10
      micrograms/kg) but were reduced by yohimbine (0.3 mg/kg). 2. Pressor responses to
      noradrenaline (0.1 micrograms/kg), phenylephrine (1 micrograms/kg) and
      vasopressin (10 mU/kg) were enhanced during infusions of UK14304 (0.03-1
      micrograms/kg per min). Likewise, pressor responses to spinal sympathetic
      stimulation were enhanced during infusions of low concentrations of UK14304 (0.03
      0.3 microgram/kg per min) but were reduced during infusion of a higher
      concentration of UK14304 (10 micrograms/kg per min). 3. After administration of
      yohimbine (0.3 mg/kg) or the calcium channel blocking drug diltiazem (infused at
      50 micrograms/kg per min), pressor responses to noradrenaline and UK14304 were
      reduced, and responses to noradrenaline during infusion of UK14304 were not
      enhanced. 4. Prazosin (10 micrograms/kg) revealed a secondary depressor component
      in the response to sympathetic stimulation which is due to beta-adrenoceptor
      activation, since it was abolished by ICI 118551 (0.3 mg/kg). In the presence of
      ICI 118551 plus prazosin, pressor responses to sympathetic stimulation were
      enhanced during infusions of UK14304. 5. The depressor response to nitroprusside
      and the depressor component of responses to sympathetic stimulation after
      prazosin were enhanced during infusions of UK14304 at concentrations that
      increased the blood pressure. 6. The findings show that alpha 2-adrenoceptor
      activation enhanced the pressor responses to sympathetic nerve stimulation,
      noradrenaline, phenylephrine and vasopressin in the pithed rat and beta
      adrenoceptor activation produced depressor responses which increased with
      increasing blood pressure.

PMID- 1980236
TI  - Alpha-adrenergic blockers: mechanism of action, blood pressure control, and
      effects of lipoprotein metabolism.
AB  - The sympathetic nervous system plays a major role in the pathogenesis of
      essential hypertension and is mediated by the alpha and beta receptors. The alpha
      receptor is divided into two types, alpha 1 and alpha 2, based on response to
      epinephrine and norepinephrine. alpha 1-Adrenergic receptors have a high affinity
      for drugs such as prazosin, doxazosin, and terazosin, which act to reduce blood
      pressure by selective blockade of the receptor. These agents provide a rational
      approach to the treatment of hypertension by correcting elevated total peripheral
      resistance, the fundamental hemodynamic abnormality in essential hypertension. In
      contrast, early alpha-adrenergic receptor blockers nonselectively blocked both
      alpha 1 and alpha 2 receptors and were unsuitable as antihypertensive agents
      because they induced tachycardia and patients developed a tolerance to them
      rapidly. alpha 1-Adrenergic blockers also have beneficial effects on plasma
      lipoproteins, tending to decrease levels of triglycerides and cholesterol and
      increase levels of high-density lipoprotein (HDL) cholesterol and the HDL
      cholesterol/total cholesterol ratio. beta-Adrenergic blockers, such as
      propranolol and atenolol, have been shown to have an adverse effect on the lipid
      profile by tending to increase levels of triglycerides and decrease HDL
      cholesterol. A number of mechanisms contribute to these effects, in particular,
      adrenergic modulation of lipoprotein lipase and the triglyceride secretion rate.
      Doxazosin has been shown to increase the activity of LDL receptors, which may be
      partly responsible for its beneficial effect on plasma lipids and
      lipoproteins.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1980237
TI  - Elevated c-myc messenger RNA in multiple myeloma cell lines.
AB  - Oncogene analyses of four human myeloma cell lines provided no indication of gene
      amplification or rearrangement using DNA probes for the met, raf, abl, mos, erb
      B, Her-2-neu, fos, myb-7, fms, L-myc, sis, and myb-1 genes. However, a consistent
      elevation of up to 23-fold in the level of c-myc mRNA was observed in all of the
      cell lines studied. No restriction fragment length polymorphism (in exons one,
      two, or three) or c-myc gene amplification has as yet been demonstrated to
      account for the c-myc mRNA elevation. The c-myc mRNA has a half-life of 25 min
      which is comparable to that observed in other systems. The elevation in c-myc
      mRNA is further evidence for the role of the c-myc proto-oncogene in the
      pathogenesis of myeloma.

PMID- 1980239
TI  - Polymorphisms in the gene coding for cholesteryl ester transfer protein are
      related to plasma high-density lipoprotein cholesterol and transfer protein
      activity.
AB  - 1. Cholesteryl ester transfer protein activity may have a physiological effect on
      high-density lipoprotein levels. 2. We examined restriction fragment length
      polymorphisms associated with the cholesteryl ester transfer protein gene and the
      apolipoprotein AI gene in a group of 60 unrelated subjects selected from an
      initial survey of 5000 subjects on the basis of their high-density lipoprotein
      levels being high or low at the extremes of the distribution. The activities of
      cholesteryl ester transfer protein and lecithin:cholesterol acyltransferase
      (phosphatidylcholine-sterol acyltransferase, EC 2.3.1.43) were also determined.
      Analysis by selection of those with a low high-density lipoprotein cholesterol
      level (less than or equal to 1.1 for males, less than or equal to 1.2 for
      females) gave 32 individuals with 24% B2 alleles. Selection of subjects with a
      high-density lipoprotein cholesterol level (less than or equal to 2 mmol/l) gave
      17 with 62% B2 alleles. 3. The group with low levels of high-density lipoprotein
      cholesterol had higher activity of cholesteryl ester transfer protein and
      significantly elevated triacylglycerol levels when compared with the group with
      high levels of high-density lipoprotein cholesterol. 4. A further significant
      finding was the correlation of the MspI restriction fragment length polymorphism
      detected by the apolipoprotein AI gene with lecithin:cholesterol acyltransferase
      activity.

PMID- 1980238
TI  - Independent mutations in the flanking sequence of the alpha-1-antitrypsin gene
      are associated with chronic obstructive airways disease.
AB  - Two restriction fragment length polymorphisms (RFLPs) of the flanking sequence of
      the alpha 1-antitrypsin (AAT) gene, detected with the restriction enzymes HindIII
      and TaqI, have been reported to occur more commonly in patients with chronic
      obstructive airways disease (COAD). Their frequencies were investigated in 20
      Caucasian families with a family history of COAD and in 140 unrelated COAD
      patients none of whom had AAT deficiency. The HindIII polymorphism was present in
      six index cases of 20 families (p = 0.0015) and 14 of the unrelated patients (p =
      0.061) compared with one of 60 healthy unrelated controls. The TaqI polymorphism
      was present in five of 101 healthy unrelated controls and in three index cases of
      the 20 families. In the unrelated patient group 28 of 140 had the polymorphism
      (chi 2 = 10.01, p = 0.0016) and corresponds to a mean log odds ratio of 1.56 (95
      per cent confidence limits of 0.58-2.56). The polymorphisms occurred
      independently of each other and were not associated with AAT deficiency in the
      basal state.

PMID- 1980240
TI  - Use of beta-adrenergic blocking agents in congestive heart failure.
AB  - The use of beta-adrenergic blocking agents in patients with congestive heart
      failure (CHF) is reviewed. The sympathetic nervous system plays an important
      compensatory role in maintaining inotropic support of the failing heart;
      therefore, beta blockers have long been considered contraindicated in CHF
      patients. However, prolonged excessive activation of the sympathetic nervous
      system may be detrimental. Several clinical trials have shown improved functional
      status and hemodynamic indices in some patients with dilated cardiomyopathy who
      received beta blockers. The maximum effect required up to 12 months. Two studies
      also showed trends toward improved survival. Aspects of study design that appear
      to be associated with the observation of a favorable response to beta blockade in
      CHF patients are a low initial dosage, gradual adjustment of the dosage, and a
      sufficient duration of therapy. Trials with unfavorable results lacked one or
      more of those design characteristics. Mechanisms proposed to underlie the
      beneficial effects of beta blockers in CHF patients include up-regulation of beta
      receptors, reduction in cardiac energy requirements, protection of the myocardium
      against norepinephrine toxicity, and anti-arrhythmic effects. Most studies were
      conducted in patients with idiopathic dilated cardiomyopathy; it is unknown
      whether beta-blocker therapy is equally beneficial in patients with CHF arising
      from other causes. Metoprolol is the agent for which there is the most
      experience; comparative efficacy trials have not been conducted. Beta-adrenergic
      blockers appear to be beneficial in some patients with CHF. Further trials are
      needed to identify the patients most likely to respond and the drugs most likely
      to work.

PMID- 1980241
TI  - Psychotropic medication in the elderly. A survey of prescribing and clinical
      outcome.
AB  - Due to the increasing elderly population, an increased number of elderly patients
      requires treatment for mental and behavioural disorders. There are relatively few
      clinical studies of the prescribing of psychotropic drugs in patients over 65
      years of age. A prospective study was undertaken at three centres caring for the
      elderly, encompassing patients from general nursing homes and a psychiatric
      department. Entry of patients into the survey was determined by the clinical
      decision to prescribe psychotropic medication and an age of 65 years or older.
      Included in the study were 160 patients. The main reasons for initiating
      psychotropic medication were indicated, and anamnestic data were collected.
      Initial and continuing dosages of psychotropic medication were recorded. The
      clinical condition was assessed at the start of treatment and after four and
      eight weeks, utilising the Clinical Global Impressions (CGI) scale. The patient's
      daily activity using an abbreviated Stockton Geriatric Rating Scale (SGRS) was
      assessed. Side effects were recorded using the UKU Scale. Clinical improvement
      was seen in about half of the patients with the best effect in patients with
      mainly psychotic symptoms. Patients with chronic dementia-related problems
      responded less well. Side effects were few and generally mild. This situation may
      relate to cautious introduction of the medication and adoption of low-dose
      regimens. All centres avoided, if possible, psychotropic polypharmacy.

PMID- 1980242
TI  - Alterations of growth fraction and DNA content in K562 cells by differentiating
      agents.
AB  - The growth fraction, estimated by the monoclonal antibody Ki-67 labeling, and DNA
      content, assessed by ethidium bromide staining, were determined simultaneously in
      K562 leukemic cells by flow cytometry. A multiparametric analysis enabled the
      fraction of the cell population with G1, S, and G2 + M contents in Ki-67-positive
      and Ki-67-negative cells to be evaluated. Butyric acid (BUT) was used as positive
      control. The fraction of Ki-positive cells decreased with the BUT concentration,
      while the proportion of cells with G1 DNA content increased only in the Ki
      negative cells. Adriamycin, aclacinomycin A, and fagaronine induced
      differentiation, as assessed by benzidine staining and glycophorin A expression.
      These drugs decreased the fraction of Ki-positive cells by more than 50% for both
      anthracyclines and by 25% for fagaronine. Following treatment, Ki-negative cells
      displayed a G1, but also a G2 and a S DNA content in different proportions,
      indicating that induction of quiescent cells by differentiating agents is not a
      uniform process and is worthy of interest.

PMID- 1980244
TI  - Radiation-induced cell transformation: transformation efficiencies of different
      types of ionizing radiation and molecular changes in radiation transformants and
      tumor cell lines.
AB  - This study aims to compare the efficiencies of 5.4 keV soft X-rays, alpha
      particles, and gamma-rays in transforming C3H 10T1/2 cells and to assess the
      sequence of cellular and molecular changes during the process of radiation
      induced transformation of Syrian hamster embryo (SHE) cells. The somewhat more
      densely ionizing soft X-rays are more effective than gamma-rays both for cell
      inactivation and cell transformation. The relative biological effectiveness (RBE)
      appears to be independent of dose; it is approximately 1.3 for either end point.
      The RBE of alpha-particles versus gamma-rays, on the other hand, increases with
      decreasing dose; the dose dependence is somewhat more apparent for cell
      transformation than for cell inactivation. SHE cells transformed by different
      types of ionizing radiation and related tumor cell lines isolated from nude mice
      tumors were found to have a distinct growth advantage compared to primary SHE
      cells, documented by higher plating efficiencies, shorter doubling times, and
      higher cloning efficiencies in semisolid medium. Most transformed and tumor cell
      lines that were investigated have elevated mRNA levels for the H-ras gene, some
      of them show restriction fragment length polymorphisms of the H-ras gene, and
      some exhibit a substantially amplified c-myc gene. In a sequence analysis of the
      Syrian hamster H-ras gene of eight tumor cell lines from radiation transformants,
      we have not found any mutation in codons 12, 13, 59, 61, nor in the flanking
      regions of these codons. The transformed and tumor cell lines tend to have lower
      chromosome numbers than primary SHE cells.

PMID- 1980243
TI  - [The role of disorders in the central mechanisms of neurohumoral regulation in
      the outcome of a viral infection (experimental influenza)].

PMID- 1980245
TI  - Increased aspartic acid release from the iron-induced epileptogenic focus.
AB  - Evidence has been growing in recent years for the involvement of excitatory
      neurotransmitter amino acids in the etiology of epilepsy. The precise mechanism
      of this involvement, however, remains unknown. In the present study, in vitro
      release and uptake of [3H]aspartic acid and [3H]glutamic acid were investigated
      in focal cerebral cortex in the iron-induced model of post-traumatic epilepsy in
      the rat. The animals were injected with FeCl3 or saline into the cerebral cortex
      and release and uptake studied in cortical slices from both acute and chronic
      foci (30 min and 3 weeks post injection, respectively), using a superfusion
      system. The results showed: (a) a significant increase in K(+)-stimulated
      aspartic acid release from the acute iron injected focus as compared to the
      corresponding saline injected cortex; and (b) no significant differences in the
      release of glutamic acid or in the uptake of glutamic acid and aspartic acid
      between the iron injected and the saline injected cortex. The finding of
      increased aspartic acid release suggests that this amino acid may play a role in
      the mechanism of iron-induced epilepsy in the rat.

PMID- 1980246
TI  - The excitatory amino acid antagonist amino-phosphono-valeric acid (APV) provides
      protection against penicillin-induced epileptic activity in the rat.
AB  - The effects of intraperitoneal injection of 2-amino-5-phosphono-valeric acid
      (APV) on EEG-monitored penicillin-induced epileptic activity in rats were
      evaluated. A significant decrease in the frequency of spikes occurred with low
      APV dosages (10 and 20 mg/kg), while an almost complete disappearance of spike
      activity was observed at higher APV doses (40 and 160 mg/kg). Our data suggest
      that excitatory amino acids play a relevant role in penicillin-induced epileptic
      activity in rats.

PMID- 1980247
TI  - Receptor site specificity for the acute effects of beta-N-methylamino-alanine in
      mice.
AB  - DL-beta-N-methylamino-alanine (DL-BMAA; 1-10 mumol i.c.v.) in mice induced a
      syndrome of: ataxia, ptosis, scratching, jumping, myoclonic jerks, clonic muscle
      spasms and tonic seizure, which was unaffected by pretreatment with D(-)-4-(3
      phosphonoprop-2-enyl)-piperazine-2-carboxylate (D(-)-CPPene; i.p.), or by co
      administration of gamma-D-glutamylamino-methylsulphonate (gamma-D-GAMS with DL
      BMAA; i.c.v.). Pretreatment with 1-(aminophenyl)-4-methyl-7,8-methylendioxy-5H
      2,3-benzodiazepine (GYKI 52466; i.v.) decreased the incidence of clonic seizures
      for DL-BMAA, kainic acid and RS-alpha-amino-3-hydroxy-5-methyl-4-isoxazole
      propionate (RS-AMPA; i.c.v.). These results suggest an involvement of the
      AMPA/quisqualate subtype of excitatory amino acid receptors in acute BMAA
      toxicity.

PMID- 1980248
TI  - Lack of a dopamine autoreceptor selective profile of B-HT 920 in functional in
      vitro model systems of D2 receptors in rat striatum.
AB  - Based on the results of in vivo studies, the thiazoloazepine derivative B-HT 920
      has been proposed to be a selective agonist of dopamine autoreceptors. In the
      present study, we investigated the effects of B-HT 920 in two functional in vitro
      model systems of D2 receptors and compared these effects with the effects of the
      classical D2 agonist LY 171555. B-HT 920 and LY 171555 concentration dependently
      inhibited the electrically evoked release of radiolabeled dopamine and
      acetylcholine and the forskolin-induced stimulation of adenylate cyclase activity
      in rat striatal tissue slices with comparable efficacies. In striatal tissue
      slices prepared after 6-hydroxydopamine-induced destruction of dopaminergic
      terminals, both drugs were still able to inhibit forskolin-stimulated adenylate
      cyclase activity with a efficacy similar to that in tissue obtained from
      unlesioned rats. It is concluded that, in vitro, B-HT 920 is an agonist at both
      presynaptic and 'normosensitive' postsynaptic D2 receptors showing relatively
      high intrinsic activity.

PMID- 1980250
TI  - Catecholamines, opioid peptides, and true opiates in the chromaffin cells of the
      eel: immunohistochemical evidence.
AB  - An immunohistological analysis of the chromaffin cell system of the American eel
      revealed the presence of tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase
      (DBH) in all cells. However, phenylethanolamine-N-methyltransferase (PNMT) was
      seen only in a fraction of the chromaffin cells. This suggests the presence of
      both norepinephrine and epinephrine cells and the absence of specific dopamine
      cells. The chromaffin cells are most numerous in the anterior region of the
      posterior cardinal vein, where they occupy a subendothelial position. Their
      number decreases caudally, and a relatively small number are present in the
      larger veins of the opisthonephric kidney. No PNMT-positive cells were identified
      in this region, although a radioenzymatic assay had previously shown the presence
      of epinephrine. Methionine-enkephalin immunoreactivity seems to be restricted to
      the chromaffin cells. However, particularly large amounts of leucine
      immunoreactivity occur in the interrenal cells, with smaller quantities in the
      chromaffin cells. The chromaffin cells of the eel also contain morphine
      immunoreactivity.

PMID- 1980249
TI  - [Changes in hormone and neurotransmitter action with aging].
AB  - The paper is concerned with the mechanisms underlying an interaction between
      hormones and neurotransmitters and the specific receptors of glandular and
      nervous tissues during aging. The heterogeneous++ pattern of age changes in
      different receptors and in different tissues in described. Most prevalent are the
      phenomena of the reduced number of receptors but not their affinity, and at the
      postreceptor level--the deranged capacity of calcium mobilization. The
      possibility of correction of age changes in hormonal and neurotransmitter
      actions, both at the receptor and postreceptor level, is stressed.

PMID- 1980252
TI  - High transformation frequency of nonsporulating mutants of Streptomyces griseus.
AB  - Three different bld mutants from S. griseus ATCC 10137 were isolated by
      nitrosoguanidine mutagenesis. They simultaneously lost the capability of
      antibiotic production and the formation of pigments. The three bld mutants were
      differently affected by different carbon sources. Two of these mutants showed a
      high efficiency of transformation with several plasmid vectors, in contrast to
      the low efficiency of transformation showed by the wild type. We showed that S.
      griseus ATCC 10137 and the three bld mutants possess an enzymatic activity that
      protects their DNAs against the digestion by SacI. Antibiotic and pigment
      production, and low transformability with plasmid DNA were together restored in
      spontaneous spo+ revertants.

PMID- 1980251
TI  - Stimulants of ileal salt transport in neuroendocrine system of the desert locust.
AB  - Proteinaceous factors from the corpora cardiaca (CC) and ventral ganglia (VG)
      stimulate KCl transport across voltage-clamped preparations of locust ilea in a
      dose-dependent manner. These factors may act via cAMP as the second messenger
      because this cyclic nucleotide and agents which increase its cellular level all
      mimic the stimulatory effects of CC and VG extracts. The CC and VG factors are
      apparently different compounds because they differ in the time course of ileal
      short-circuit current (Isc) initiated, in heat stability, and in extraction
      properties. Because saline extracts of the CC have similar effects on both ileal
      and rectal segments of locust hindgut, the ileal stimulant from the CC may be the
      chloride transport-stimulating hormone, described by Phillips et al. (Canad. J.
      Zool. 58, 1851-1860, 1980) which acts to stimulate rectal Isc.

PMID- 1980253
TI  - A cloned chromosomal DNA fragment which differentiates Yersinia pestis from
      Yersinia pseudotuberculosis and Yersinia enterocolitica.
AB  - Chromosomal DNA from reference Yersinia strains was digested individually with 9
      restriction endonucleases. DNA fragments were separated and analyzed by
      electrophoresis through agarose gels. The clearest fragment patterns were
      obtained when EcoRI was employed. The Y. pestis fragment pattern obtained after
      the use of this enzyme showed the presence of a unique DNA fragment with
      molecular mass 1400 bp. This DNA fragment was cloned, purified, labeled with 32P
      and then used to probe EcoRI digests of all three Yersinia species. A strong
      hybridization signal was obtained with Y. pestis strain. No such signal was found
      with Y. pseudotuberculosis or Y. enterocolitica. These results indicate that the
      DNA fragment is species specific and could be used as a diagnostic DNA probe for
      Y. pestis.

PMID- 1980254
TI  - Limited repertoire of the C-terminal region of the M protein in Streptococcus
      pyogenes.
AB  - We have amplified genomic sequences (emm) that may encode M protein from strains
      of Streptococcus pyogenes using the polymerase chain reaction (PCR). Genomic DNA
      from 22 isolates representing 14 M serotypes was selected for the study. Primers
      which corresponded to the observed N-terminal signal sequence and the variable C
      terminal sequences of emm6, emm49 and ennX were used. PCR products using emm6 and
      emm49 oligonucleotides were classified into two mutually exclusive groups which
      correspond to the presence or absence of serum opacity factor. These findings
      support the concept of limited heterogeneity in the C-terminal sequences of the M
      protein.

PMID- 1980255
TI  - [Pharmacological properties of (+/-)-4-[2-hydroxy-3-(3-(2-methoxyphenoxy)-2
      propylamino)propoxy]-1(2H) -isoquinolinone (N-1518), a new combined alpha- and
      beta-adrenoceptor blocking drug].
AB  - The alpha, beta-adrenergic blocking, antihypertensive and vasodilating properties
      of N-1518 were compared with those of labetalol. N-1518 blocked alpha- and beta
      adrenoceptors competitively as indicated by parallel rightward displacement of
      the dose-response curve of each agonist in isolated organs and in anesthetized
      dogs. As judged by pA2 values and DR10 values, N-1518 was as potent as labetalol
      in blocking alpha- and beta-adrenoceptors. The beta 1/alpha 1 ratio of N-1518 was
      8.3 for pA2 values in isolated organs and 13.6 for DR10 values in anesthetized
      dogs, respectively. N-1518 inhibited dose-dependently the pressor response to
      intravenous administration of noradrenaline, but labetalol did not depress the
      response to noradrenaline in anesthetized dogs. N-1518 is composed of four
      optical isomers. The SR-isomer was the most potent in blocking beta-receptors,
      and the RR-isomer was the most potent in blocking alpha-receptors. N-1518 has no
      intrinsic sympathomimetic activity in reserpinized rats and has no local
      anesthetic activity in guinea pigs. Single oral administration of N-1518 produced
      a fall in blood pressure in conscious SHR and renal hypertensive dogs without
      causing tachycardia. Intra-arterially administered N-1518 in the dog hindlimb
      resulted in vasodilation as indicated by the increase in blood flow. The
      magnitude of the responses was approximately 3 times more potent than that of
      labetalol.

PMID- 1980257
TI  - Re-evaluation of current methodology of toxicity testing including gross
      nutrients. 5-7 April 1989, Belgium. Proceedings.

PMID- 1980256
TI  - [Antihypertensive effect of naftopidil (KT-611), a novel alpha 1-adrenoceptor
      antagonist, in freely moving experimental hypertensive rats and dogs].
AB  - The antihypertensive effect of naftopidil (KT-611) following single oral
      administration was investigated in normotensive Wistar Kyoto rats (WKY),
      spontaneously hypertensive rats (SHR), DOCA-Salt hypertensive rats (DHR), 2
      kidney 1-clip renal hypertensive rats (RHR) and Grollman type renal hypertensive
      dogs with 1-kidney (RHD); and it was compared with that of the selective alpha 1
      adrenoceptor antagonist prazosin. The blood pressure and heart rate were measured
      under the unanesthetized, unrestrained state through an arterial catheter that
      was chronically implanted into the abdominal aorta. In SHR and WKY, both KT-611
      (10 and 30 mg/kg, p.o.) and prazosin (1 and 3 mg/kg, p.o.) markedly inhibited the
      pressor response to the alpha 1-adrenoceptor agonist phenylephrine (3
      micrograms/kg, i.v.). KT-611 (10 to 100 mg/kg, p.o.) showed a dose-dependent
      hypotensive effect in SHR, DHR and RHR but not in WKY. The hypotensive effect of
      KT-611 reached maximum at 0.5-1 hr, lasted for 4-6 hr and was more potent in DHR
      and RHR than in SHR. The potency of KT-611 was 1/10-1/30 weaker than that of
      prazosin. In RHD, single oral administration of KT-611 (1 to 10 mg/kg) caused a
      dose-dependent and long-lasting hypotensive effect. These results suggest that KT
      611 has a long-lasting hypotensive effect in experimental hypertensive animal
      models.

PMID- 1980258
TI  - Exogenous somatostatin raises plasma insulin levels in patients with insulin
      dependent diabetes mellitus.
AB  - The effect of cyclic somatostatin on circulating insulin levels was studied in
      eight patients with insulin-dependent diabetes mellitus (IDDM). The study was
      performed after an overnight fast when their subcutaneous depots of insulin had
      been depleted during i.v. insulin substitution for 18 hours. A constant rate i.v.
      insulin infusion (0.4 mU/kg/min) was given for 240 min and somatostatin was co
      infused between 60-120 min (100 micrograms/h) and 180-240 min (250 micrograms/h)
      respectively. Plasma insulin, blood glucose and hematocrit were measured at 15
      min intervals. Hematocrit fell from 41.7 to 38.3% during the study period.
      Somatostatin increased the plasma insulin levels, corrected for the changes of
      hematocrit, by approximately 8% in the low dose (P less than 0.05) as well as in
      the high dose (P less than 0.05) period. It is concluded that somatostatin
      interferes with the clearance of insulin thereby increasing the circulating
      plasma insulin levels in IDDM patients without residual insulin secretion.

PMID- 1980259
TI  - Normal inhibition by somatostatin of glucose-stimulated B cell secretion in the
      obese subjects.
AB  - Aim of the present study was to evaluate whether the inhibitory effect of
      somatostatin on pancreatic B-cell secretion is normal in nondiabetic obese
      subjects. For this purpose plasma C-peptide concentrations were measured in 10
      nondiabetic obese subjects and 10 nonobese healthy controls during a 4-h
      hyperglycemic (11 mmol/l) glucose clamp. Somatostatin was infused (2.5 nmol/min)
      during the third hour of the study period in order to inhibit glucose-stimulated
      B-cell secretion. Fasting C-peptide averaged 0.46 +/- 0.04 nmol/l (mean +/- SEM)
      in nonobese subjects, and 0.85 +/- 0.08 nmol/l in obese patients (P less than
      0.001). In the period 0-120 min the area under the plasma C-peptide curve was
      significantly higher in obese than in nonobese subjects (292 +/- 23 vs. 230 +/-
      17 nmol/l x 120 min, P less than 0.05), however, in the last 20 min of the
      glucose infusion period without somatostatin (100-120 min) plasma C-peptide was
      not significantly different in the two groups (2.94 +/- 0.32 nmol/l in nonobese
      subjects and 3.21 +/- 0.19 nmol/l in obese patients, p = NS). During somatostatin
      infusion while maintaining hyperglycemia, plasma C-peptide decreased in both
      groups, and in the period 160-180 min it averaged 0.89 +/- 0.12 nmol/l in control
      subjects and 0.93 +/- 0.08 nmol/l in obese patients (P = NS), with a percent
      reduction similar in the two groups (70 +/- 2% in controls and 71 +/- 2% in obese
      patients). After discontinuing somatostatin infusion, plasma C-peptide increased
      to concentrations which were higher in obese than in nonobese subjects.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1980260
TI  - Effects of pancreastatin on pancreatic hormone secretion in the dog.
AB  - In the anaesthetized dog, porcine pancreastatin (98 pmol/min) was infused for 10
      min into the pancreaticoduodenal artery either alone or during infusion of
      glucose. Blood was sampled from the pancreaticoduodenal vein. We found that
      pancreastatin inhibited pancreatic insulin output only under normoglycaemic
      conditions. Furthermore, pancreastatin significantly stimulated pancreatic
      glucagon and somatostatin outputs both during normo- and hyperglycaemic
      conditions. Our results show that pancreastatin has the capability to affect
      directly the three pancreatic hormone secretions in dogs.

PMID- 1980261
TI  - Mechanism of action of growth-hormone-releasing hormone in stimulating insulin
      secretion in vitro from isolated rat islets and dispersed islet cells.
AB  - Human growth-hormone-releasing hormone [(1-44)NH2] (hGHRH) was a potent stimulus
      for insulin release from rat islets of Langerhans in vitro; the optimum
      concentration used was 10(-11) M. The dose response curves for hGHRH effects on
      insulin secretion were notably different in intact islets of Langerhans compared
      to cultured dispersed islet cells. Pancreatic islets responded to a very low
      hGHRH concentration (10(-12) M), but at a higher hGHRH concentration (10(-9) M)
      no stimulation of insulin release was observed. When somatostatin antiserum was
      included in the incubation medium, hGHRH (10(-9) M) stimulated insulin release
      from intact islets. In cultured dispersed islet cells, which are principally
      insulin-secreting B cells, hGHRH directly and potently stimulated insulin release
      even at a concentration of 10(-9) M. Addition of somatostatin (10(-7), 10(-8) M)
      significantly reduced the hGHRH-induced insulin-secretory responses of dispersed
      islet cells. hGHRH (10(-11)-10(-9) M) raised islet cAMP levels; individually,
      hGHRH and theophylline exerted positive effects on insulin release, their
      combined effect was greater than that caused by either one. We conclude that
      hGHRH directly affects insulin secretion in vitro by a cAMP-dependent mechanism,
      and that the difference in responses of intact islets versus islet cells to
      increasing concentrations of hGHRH may be related to hGHRH-induced release of
      somatostatin in intact rat islets.

PMID- 1980262
TI  - Computers and quantitative approaches to diabetes. An international symposium.
      Sydney, Australia, November 1988. Proceedings.

PMID- 1980263
TI  - Model-based analysis of CD4+ lymphocyte dynamics in HIV infected individuals.
AB  - The previously suggested mathematical model of CD4+ lymphocyte depletion in HIV
      infected individuals is analyzed and further developed. The model assumes that
      CD4+ lymphocyte depletion is caused by HIV products. Fairly good simulation of
      CD4+ lymphocyte dynamics is obtained, when limitation of HIV growth by specific
      cytotoxic T cells is included in the model. As it is probable that the
      substantial decrease of CD4+ lymphocytes, this type of influx control mechanism
      is also included in the model. It is shown that the simulated CD4+ lymphocyte
      dynamics agree with the observed data, analogously as in the earlier considered
      case of the constant influx. Moreover, the depleting effect of HIV products on
      mature and/or immature CD4+ lymphocytes is analyzed by the model. Also, another
      modification of the model assuming that CD4+ lymphocyte depletion is due to their
      destruction by cytotoxic T cells specific for HIV antigens, gives simulation
      results comparable to those obtained by the original version of the model, where
      the mechanism of the depletion is not specified.

PMID- 1980265
TI  - Central modulation of croton oil induced subacute inflammation in rats.
AB  - Earlier studies from this laboratory have indicated that CNS exerts a modulatory
      influence over acute inflammation in rats. The present study examines the
      existence of a similar modulatory effect of CNS on a subacute inflammatory
      paradigm, the croton oil-induced granuloma pouch in rats. The inflammatory
      exudate, collected on 6th day after croton oil administration, was found to be
      substantially less in intracerebroventricular (icv) cannulated and artificial
      cerebrospinal fluid administered rats as compared to their uncannulated saline
      (ip) administered counterparts. This effect may be due to stress induced by
      cannulation. Centrally administered pharmacological agents which attenuate
      central monoaminergic, cholinergic or prostaglandin systems had insignificant
      effects on the inflammatory exudate. However, induced increase in central
      noradrenergic activity was found to attenuate the inflammation when the treatment
      was done before, but not 48 hr after, the induction of the inflammation. In
      contrast, induced increase in central serotonergic activity had no effect on the
      volume of the inflammatory exudate at either time period. Steady state levels of
      rat brain noradrenaline and serotonin, but not dopamine, were enhanced by the
      inflammatory procedure. However, these effects may be attributed to the stress
      induced by croton oil inflammation. The investigation indicates that the
      modulatory influence of CNS remains limited to the acute phase of inflammation,
      being exerted mainly by the central noradrenergic system. Once the inflammation
      has progressed, this modulatory influence of CNS is no longer apparent.

PMID- 1980264
TI  - Divergent regulation of beta 2-adrenoceptors and adenylate cyclase in the Cyc-
      mouse T lymphoma cell line TL2-9.
AB  - The radiation leukemia virus-induced murine Cyc- T lymphoma cell line TL2-9
      expressed one homogeneous population of beta 2-adrenoceptors based on competition
      curves of [125I]cyanopindolol with the specific antagonist ICI 118.551 and three
      beta-adrenergic agonists. These receptors were uncoupled from adenylate cyclase
      due to the absence of Gs. The catalytical unit was directly stimulated by MnCl2,
      forskolin, and even more markedly in the simultaneous presence of both reagents.
      In contrast, the enzyme was inhibited in the presence of Gpp[NH]p, probably
      through interaction with Gi. Indeed, this inhibitory effect was constrained by
      preincubating cells in the presence of pertussis toxin and a 41 kDa protein was
      specifically ADP-ribosylated in the presence of the toxin. This cell line was
      therefore analogous to the Cyc- cell line derived from the murine S49 lymphoma
      cell line. When added to the culture medium, butyrate (2 mM) induced beta 2
      adrenoceptors, the expression of these uncoupled receptors depending on protein
      synthesis, as judged by inhibitory effects of cycloheximide. In contrast, dBcAMP
      (1 mM) and TPA (tumor-promoting agent phorbol ester) increased the rate of
      disappearance of beta 2-adrenoceptors. Butyrate, dBcAMP and TPA systematically
      decreased adenylate cyclase activity. Besides, TPA (but neither butyrate nor
      dBcAMP) reduced the efficacy of Gpp[NH]p in inhibiting adenylate cyclase,
      suggesting a proportionately higher alteration of Gi. We conclude that beta 2
      adrenoceptors, uncoupled from adenylate cyclase, are regulated independently from
      the catalytical unit and Gi, in this Cyc- T lymphoma cell line.

PMID- 1980266
TI  - Dose related protective effect of azelastine on histamine induced
      bronchoconstriction in extrinsic asthma.
AB  - The effect of single oral doses of the antiallergic agent azelastine
      hydrochloride (1.1, 2.2 and 4.4 mg) was compared to placebo on airway response to
      histamine challenge in 12 asymptomatic extrinsic asthmatics with proven bronchial
      hyperresponsiveness to inhaled histamine in a randomized double-blind crossover
      trial. All doses of azelastine resulted in a significant protection compared to
      placebo. The effects of 2.2 and 4.4 mg were equivalent and superior compared to
      1.1 mg. A naturally small but statistically significant bronchodilator effect was
      observed 4 h after the two higher doses of azelastine. Tiredness was reported by
      two patients, the symptom occurred following each placebo and the active drug.

PMID- 1980267
TI  - Cutaneous periarteritis nodosa.

PMID- 1980268
TI  - The use of sulfasalazine in atrophie blanche.
AB  - Atrophie blanche can be a chronic condition for which there is no satisfactory
      treatment. Two patients with atrophie blanche who had not responded to various
      therapeutic modalities were given a trial of sulfasalazine 1 g three times daily.
      The ulcers healed within 3 months in both cases. In view of these positive
      results, patients should be treated with sulfasalazine to determine the efficacy
      of this drug in atrophie blanche.

PMID- 1980269
TI  - Synthesis and 11C-labelling of the ACTH fragment analogue H-Met(O2)-Glu-His-Phe-D
      Lys-Phe-OH (Org 2766) via its homocystine-containing precursor.
AB  - The hexapeptide dimer (H-Hcy-Glu-His-Phe-D-Lys-Phe-OH)2 was synthesized using
      solution methods and characterized. Its conversion into H-Met(O2)-Glu-His-Phe-D
      Lys-Phe-OH, Org 2766, was studied on a small scale in as short a time as
      possible; reduction of the disulfide bond using Na/NH3, reaction with CH3I,
      oxidation with H2O2 and catalyst and purification by HPLC were carried out
      starting with 2 mg of the dimer in a total preparation time of approximately 22
      min, starting with the addition of CH3I. The preparation of the 11C-labelled
      analogue was carried out by methylation with 11CH3I. Restrictions imposed by
      working with carbon-11 will be discussed.

PMID- 1980270
TI  - Relationship of neuroleptic-induced akathisia to drug-induced parkinsonism.
AB  - Akathisia refers to subjective inner restlessness and a feeling of the need to
      move. Its occurrence in association with Parkinson disease suggests a common
      underlying pathophysiological mechanism. We investigated the relationship of
      neuroleptic-induced akathisia to drug induced parkinsonism in a group of 123
      neuroleptic-treated elderly chronic schizophrenic inpatients (mean age: 63.9 +/-
      8.9 years). In addition, since neuroleptic-induced akathisia has been noted to be
      more common in females, we studied the severity of akathisia separately by
      gender. Akathisia was present in 40 patients (32.5%). We found no significant
      differences in the severity of akathisia between patients with and these without
      parkinsonism. Although a significantly larger proportion of females than males
      had akathisia, there were no significant differences in respect of parkinsonism.
      Our findings do not support a major role for the dopaminergic system in the
      pathophysiology of akathisia might be related to dysfunction of nondopaminergic
      systems.

PMID- 1980271
TI  - The management of acute headache: a worldwide perspective. Proceedings of an AASH
      symposium, 32nd annual meeting and advanced course, June 22nd, 1990.

PMID- 1980272
TI  - Testicular seminoma associated with torsion of the spermatic cord in two
      cryptorchid stallions.
AB  - Two adult horses had colic attributable to spermatic cord torsion and
      strangulation of abdominally retained neoplastic testes. Both horses had caudal
      abdominal soft tissue masses palpable per rectum. One horse was treated
      successfully by surgical removal of the testis, and the other was euthanatized
      without treatment. Histopathologic diagnosis of the involved testes was
      testicular seminoma. Spermatic cord torsion of an abdominally retained testis
      should be considered in the differential diagnosis of signs of abdominal pain in
      cryptorchid stallions, especially those with a palpable caudal abdominal mass.

PMID- 1980273
TI  - Morphological, histochemical and immunohistological studies of the paracervical
      ganglion in prepubertal, pregnant and adult, non-pregnant guinea-pigs.
AB  - The morphology and ultrastructure of the paracervical ganglion were examined in
      prepubertal and pregnant guinea-pigs using the light and electron microscope. The
      neuropeptide and acetylcholinesterase content of the neuronal perikarya and SIF
      cells, nerve fibres and nerve terminals of the ganglion were examined in
      prepubertal, adult, non-pregnant and pregnant guinea-pigs. The ganglion consisted
      of up to seven different sized clusters of neuronal perikarya lying parallel to
      the long axis of the uterovaginal junction, with 60 or more neuronal perikarya in
      any one cluster in the paracervical connective tissues. The number of neuronal
      perikarya within each cluster was related to the total area of each cluster. The
      light and electron microscopy of the clusters was typical of autonomic ganglia,
      though no vacuolated neurons were observed as has been reported in the rat. The
      neuropeptide and acetylcholinesterase content of the ganglionic clusters was not
      different in prepubertal and adult, non-pregnant guinea-pigs. In pregnant guinea
      pigs there was an apparent small decrease in numbers of neuronal perikarya
      containing the neuropeptides VIP, NPY or TH immunoreactivities, though no
      quantitative studies were undertaken. In pregnancy no SIF cells were detected,
      though in prepubertal and non-pregnant, adult guinea-pigs these cells contained
      TH, NPY or SP immunoreactivity.

PMID- 1980274
TI  - Enzymes of transmitter and energy metabolism in rat middle ear and extraocular
      muscles.
AB  - To further investigate the peculiar characteristics of the middle ear and
      extraocular muscles, compared to the extensively studied skeletal muscles of the
      limbs, activities of enzymes of transmitter and energy metabolism were measured
      in homogenates of these muscles from albino and pigmented rats. These activities
      were compared to those for a masticatory muscle and for three hindlimb muscles
      chosen for their preponderance of either slow oxidative, fast glycolytic, or fast
      oxidative glycolytic fibers. Activities of the neuromuscular transmitter enzymes
      choline acetyltransferase and acetylcholinesterase were relatively very high in
      the extraocular and middle ear muscles. The activity of malate dehydrogenase, an
      enzyme of oxidative energy metabolism, was as high in the extraocular,
      masticatory and stapedius muscles as in the oxidative hindlimb muscles, but was
      lower in tensor tympani. The activity of lactate dehydrogenase, an enzyme of
      glycolytic energy metabolism, was remarkably low in both middle ear muscles. The
      results are consistent with high innervation density in the extraocular and
      middle ear muscles, and highly oxidative metabolism in the extraocular and
      stapedius muscles. Metabolic differences between the stapedius and tensor tympani
      suggest a relatively more active role for the former in the function of the rat
      middle ear.

PMID- 1980275
TI  - Tumor necrosis factor enhances the neutrophil-dependent increase in endothelial
      permeability.
AB  - We examined the effect of tumor necrosis factor alpha (TNF alpha) on the increase
      in pulmonary microvascular endothelial monolayer permeability induced by
      activated neutrophils (PMN). Layering of PMN onto endothelial monolayers followed
      by activation of PMN with phorbol 12-myristate 13-acetate (PMA) increased 125I
      albumin clearance rate across the monolayers. Pretreatment of endothelial
      monolayers for 6 hr with TNF alpha (200 U/ml) potentiated the PMN-dependent
      increase in endothelial permeability, whereas 1 hr or 6 hr pretreatment of
      endothelial monolayers with 200 U/ml and 100 U/ml, respectively, TNF alpha did
      not enhance the response. Adherence of PMN to the endothelial cells was increased
      at 1 and 6 hr after TNF alpha (200 U/ml) treatment, but the adherence response
      was markedly greater following 6 hr of TNF alpha. The TNF alpha treatment of
      endothelial cells did not enhance neutrophil activation responses to PMA.
      Pretreatment of PMN with IB4, a MAb to the CD18 integrin, the common beta subunit
      of the adhesion proteins LFA-1, Mac-1, and p150,95 of PMN, reduced the increases
      in PMN adherence and the endothelial monolayer permeability induced by the 6 hr
      TNF alpha treatment. In contrast, pretreatment of PMN with OKM-1, a MAb to the
      CD11b epitope (alpha-subunit), had no effect on the adherence and the
      potentiation of the increase in permeability. The potentiation of the PMN
      dependent permeability increase and enhanced endothelial adhesivity at 6 hr after
      TNF alpha priming of endothelial cells was dependent on protein synthesis. The
      results indicate that protein synthesis-dependent expression of an endothelial
      ligand for CD18 and resultant endothelial hyperadhesiveness potentiates the PMN
      mediated increase in endothelial permeability after TNF alpha activation of
      endothelial cells. The priming of endothelial cells by TNF alpha may be a
      critical step in the mediation of endothelial injury.

PMID- 1980276
TI  - Liquid chromatographic studies on the aqueous solution conformation of
      substituted benzamides related to remoxipride.
AB  - A series of disubstituted benzamides related to the sterically hindered 2,6
      dimethoxybenzamide drugs, such as remoxipride, are prepared. The structure
      retention relationships for these compounds are studied on hydrocarbon stationary
      phases in various hydroorganic mobile phases. The 2,6-dimethoxybenzamide displays
      a very low capacity factor under these reversed-phase conditions, suggesting that
      steric crowding prevents the formation of an amide-methoxy N-H...O intramolecular
      hydrogen bond. The corresponding 2-hydroxy-6-methoxybenzamide shows a dramatic
      increase in affinity for the hydrocarbon stationary phase, which is
      characteristic of strong intramolecular hydrogen bonding in these compounds.
      These results suggest that the aromatic ring--carbonyl aqueous solution
      conformation is almost 90 degrees in amides like remoxipride and changes to
      coplanarity upon demethylation of one methoxy group.

PMID- 1980277
TI  - Interaction of neuropsychological and psychological factors in two cases of
      "space phobia".
AB  - Recent theories of psychological disorders are beginning to break down the
      traditional dichotomy between mental and physical processes. The present paper
      reports on two cases of space phobia in which this is especially apparent.
      Neuropsychological assessment indicated subtle disturbance in visuospatial
      functioning. The emotional response to this dysfunction appeared, however, to be
      somewhat excessive given the subtlety of the deficit. This is seen as a
      psychological reaction to a neuropsychological dysfunction.

PMID- 1980278
TI  - Multicenter evaluation of the hemodynamic effects of bisoprolol in patients with
      mild to moderate hypertension.
AB  - Twenty-six patients with mild-to-moderate essential hypertension participated in
      a 6-week outpatient, multicenter, randomized, double-blind, placebo-controlled
      two-way crossover study to assess the hemodynamic effects of bisoprolol (20 mg
      QD) at steady state. Hemodynamic assessments included sitting blood pressure,
      heart rate, and left-ventricular ejection fraction by radionuclide
      ventriculography after 7 days of bisoprolol or placebo at trough (24 h post-dose)
      and peak (3 h post-dose) values. The group adjusted mean ejection fraction was
      not significantly different in patients receiving bisoprolol compared with the
      placebo group at either peak or trough measurements; in fact, means in patients
      taking bisoprolol were slightly higher than in the placebo group. No symptomatic
      hypotension was documented. Blood pressure, measured 24 hours after dosing, was
      significantly lower in those receiving bisoprolol when compared with the placebo
      group, by 7.7 mm Hg and 9 mm Hg for diastolic and systolic blood pressure,
      respectively. Similarly, mean values of heart rate were 10 beats/min lower in the
      bisoprolol patients than in the placebo group. Only headache and insomnia
      occurred as adverse events. Bisoprolol (20 mg QD) effectively lowered blood
      pressure over a 24-hour period without significantly reducing ejection fraction
      or causing adverse clinical or biochemical events.

PMID- 1980280
TI  - [An analysis of the distribution by molecular weight of an aggregate of
      biologically active compounds taking into account their possible penetration
      through gap-junction channels].
AB  - Analysis of molecular weight distribution of most well-known biologically active
      compounds demonstrates that all known types of bioregulatory compounds, excluding
      most peptides, have molecular mass less than 800 Da, i.e. they may penetrate the
      gap junction channels and, hence, play a part of intratissue regulators. Possible
      consequences of the analysis performed for understanding the role of neurohumoral
      regulation in phylogenesis and ontogenesis of multicellular eukaryotes have been
      discussed.

PMID- 1980279
TI  - An intracellular study of respiratory neurons in the rostral ventrolateral
      medulla of the rat and their relationship to catecholamine-containing neurons.
AB  - Intracellular recording and labelling with Lucifer yellow of respiratory neurons
      in the rostral ventrolateral medulla were carried out in urethane-anaesthetised
      rats. A combined immunofluorescence and immunoperoxidase technique enabled an
      assessment of the tyrosine hydroxylase immunoreactivity, as well as an
      examination of the morphology of inspiratory and expiratory neurons in this part
      of the medulla oblongata. The results demonstrate: a) that respiratory neurons in
      the rostral ventrolateral medulla of the rat are intermingled with catecholamine
      containing neurons of the C1 cell group, but are not themselves catecholamine
      containing; b) that many non-spinally projecting respiratory neurons have axonal
      arborisations within the ventrolateral medulla in the same region as the C1 cell
      group, other respiratory neurons, and neurons reported to have a cardiovascular
      function; and c) that the dendrites of respiratory neurons in this region radiate
      throughout the ventrolateral medulla and frequently approach the ventral surface.

PMID- 1980281
TI  - [Phospholipid methylation and the synaptosomal uptake of mediator amino acids].
AB  - The decrease in neurotransmitter amino acid uptake was observed in rat brain
      synaptosomes incubated with S-adenosyl-L-methyl-methionine. The inhibitory effect
      of neurotransmitter as a consequence of methylation of synaptic membrane is more
      pronounced in stimulatory transmitter amino acids. The effect of phospholipids on
      amino acid uptake in rat brain synaptosomes decreases with age.

PMID- 1980282
TI  - Inhibitory effect of the somatostatin analog octreotide on rat pituitary tumor
      cell (GH3) proliferation in vitro.
AB  - The effects of somatostatin-14 (SS-14) and the somatostatin-analog octreotide
      (SMS 201-995, Sandostatin) on proliferation of GH3 pituitary tumor cells were
      investigated in vitro. SMS 201-995 exerted a significant, but transient,
      inhibition on GH3 cell growth which reached a maximum at 24 h and was no longer
      detectable at 48 h. The concentration that evoked the strongest inhibitory effect
      was 10 nM SMS 201-995, while lower and higher doses resulted in a less pronounced
      effect. The inhibitory effect SMS 201-995 exerted on cell proliferation was
      associated with a dose- and time-related reduction in both c-myc and c-fos mRNA
      levels. SS-14 had no noteworthy influence on either cell proliferation or c-myc
      and c-fos protooncogene expression. These data demonstrate that SS-analogs
      transiently inhibit pituitary tumor cell proliferation in vitro.

PMID- 1980283
TI  - A rapid method for genotyping mice for T cell receptor V beta a and V beta b
      haplotypes by PCR analysis of whole blood.
AB  - Strains of laboratory mice bearing a germline deletion of some T cell receptor V
      beta genes have proven useful in a variety of studies of T cell receptor
      function. Analysis of genetic crosses between deleted and wild type strains can
      provide information about the relevance of genes located within the deletion to
      specific T cell responses. Existing techniques for genotyping offspring of such
      crosses usually involve flow cytometric analysis which may not be available to
      all laboratories. Recent nucleotide sequence data indicate the presence of two
      restriction enzyme site polymorphisms in the closely linked V beta 1 gene which
      discriminate between deleted and wild-type strains. Amplification of a DNA
      segment containing the diagnostic sites by polymerase chain reaction followed by
      restriction enzyme digestion of the product offers a simple and rapid method for
      genotyping animals.

PMID- 1980284
TI  - Effect of compression speed on the tensile strength of tablets of binary mixtures
      containing aspirin.
AB  - Mixtures of aspirin with sodium chloride, sucrose, Starch 1500 or Emcompress have
      been compressed to two maximum upper punch pressures at two compression speeds.
      Non-linear relationships between tensile strength and composition, and tablet
      porosity and composition were found in all cases. Tablets of the individual
      materials compressed at fast speed showed either little change or a reduction in
      tensile strength when compared with those compressed at slow speed. For mixtures
      of aspirin with Starch 1500, tablets compressed at fast speed were weaker and
      more porous than those compressed at slow speed. However, some mixtures of
      aspirin with sodium chloride, sucrose or Emcompress gave tablets with greater
      tensile strength and lower porosity when prepared at fast compression speed
      compared with tablets prepared at slow speed. This behaviour was attributed to
      the modification of the consolidation behaviour of the aspirin by the second
      material.

PMID- 1980285
TI  - Evaluation of in-vitro percutaneous absorption across human skin and in animal
      models.
AB  - The in-vitro permeability characteristics of human skin have been examined and
      compared with results in laboratory animals using various types of penetration
      enhancers. The study was focused on evaluation of predictable validity of the
      data obtained in animals mostly used in permeation studies. The results in man
      using the same penetration enhancers were about 30% of the value in the rat. The
      least potent enhancer was dimethylsulphoxide and the maximum efficacy was
      observed with sodium laurylsulphate in the rat experiments while in man the
      results were approximately equal when using any of the studied enhancers.
      Comparison of the results of experiments performed with N-methyl-2-pyrrolidone in
      several laboratory animals and man showed that the skin permeability in man is
      approximately 4 times lower than with the rat. Man and guinea-pig were not
      significantly different in these experiments. There were no significant
      differences in laurocapram penetration enhancing effect in the concentration
      range 0.1 to 0.5%, but there was an optimum concentration of laurocapram of 1%.
      The results showed quantitative differences in percutaneous absorption in various
      animal species in comparison with man. These differences should be considered in
      selecting a suitable model for preclinical drug evaluation. The guinea-pig skin
      penetration seems to be most similar to that in man.

PMID- 1980286
TI  - Erythrocytes as carriers for L-asparaginase. Methodological and mouse in-vivo
      studies.
AB  - L-Asparaginase has been encapsulated in Swiss mouse or human erythrocytes by
      hypotonic haemolysis followed by isotonic resealing and reannealing. The details
      of incorporation and properties of carrier erythrocytes are presented. When L
      asparaginase loaded into 51Cr-labelled erythrocytes, was infused intravenously,
      the same half-life was found for asparaginase and 51Cr. In addition, L
      asparaginase loaded into erythrocytes was much more effective in eliminating
      plasma asparagine compared with the same dose of free L-asparaginase injected in
      solution, during a sustained period (14 days).

PMID- 1980287
TI  - Influence of the endothelium on vascular responses of aortae from endotoxic rats.
AB  - Intraperitoneal injection of endotoxin diminished the in-vitro contractile
      response of rat aorta to phenylephrine or clonidine, whether the intimal layer
      was disrupted or not. The relaxing responses to acetylcholine and sodium
      nitroprusside in aorta precontracted with 10(-6) M phenylephrine were similar
      between control and endotoxic groups. However, when the precontractile force
      following phenylephrine was adjusted to an equivalent level, the relaxing
      responses to acetylcholine and sodium nitroprusside were diminished in the
      endotoxic aorta compared with the controls. There was no significant difference
      between the two groups in the increase in cyclic GMP levels induced by
      acetylcholine or by sodium nitroprusside. These results suggest that aortae from
      endotoxic rats show decreased responsiveness to alpha-adrenoceptor stimulation
      not because of enhancement of the endothelium-derived relaxing factor but because
      of abnormality in the vascular smooth muscle which is not specific for subtypes
      of the alpha-adrenoceptor.

PMID- 1980289
TI  - The effect of some anti-inflammatory agents on elastase release from neutrophils
      in-vitro.
AB  - In view of the potential role of released polymorphonuclear leucocyte elastase in
      causing tissue damage, the effect of commonly used anti-inflammatory drugs on
      elastase release from neutrophils has been studied in-vitro. Elastase release
      from neutrophils exposed to the synthetic bacterial cell wall peptide N-formyl-L
      methionyl-L-leucyl-L-phenylalanine (10(-6) M) was quantitated using a radiometric
      immunoassay and a functional assay of elastase. Prednisolone and non-steroidal
      anti-inflammatory drugs inhibited elastase release at concentrations from 0.1 mM
      0.1 nM. No inhibition by sulphosalicylic acid, D-penicillamine or chloroquine
      sulphate was observed. The clinical relevance of these findings is discussed.

PMID- 1980288
TI  - Role of presynaptic purinoceptors and cyclic AMP on the noradrenaline release in
      cat cerebral arteries.
AB  - Field electrical stimulation (ES), K+ (50 mM) or ionophore X-537A (0.01 mM)
      induced tritium release from cat cerebral arteries preincubated with
      [3H]noradrenaline (NA). Adenosine and AMP (0.5 mM) did not modify tritium release
      caused by ionophore X-537A, but these agents and ATP (0.5 mM) significantly
      reduced that elicited by ES and K+; this reduction was antagonized by 1-methyl-3
      isobutylxanthine (MIX; 0.05 mM). Inosine (0.5 mM) and the agonist of purinergic
      A2-receptors, 5'N-ethyl-carboxamide adenosine (NECA; 0.5 mM) had no effect, but
      the agonist of purinergic A2-receptors L-N6-phenylisopropyl adenosine (L-PIA; 0.1
      mM) diminished tritium efflux caused by ES and K+. The adenosine inhibition of ES
      induced radioactivity release was not affected by indomethacin (0.05 mM). MIX
      (0.05 mM) increased tritium release evoked by ES and K+. Agents that increase
      intracellular cyclic (c)AMP levels, such as dibutyryl cAMP (0.5 mM), the
      phosphodiesterase inhibitor Ro 20-1724 (0.1 mM), and the activators of adenylate
      cyclase, forskolin (0.005 mM) and NaF (2 mM) reduced tritium secretion elicited
      by ES and K+. However, the intracellular increase of cyclic GMP (cGMP) caused by
      8-Br-cGMP did not affect this secretion. Dipyridamole (0.05 mM) and the adenosine
      deaminase inhibitor erythro-9-2-hydroxy-3 nonyl adenosine (EHNA; 0.1 mM) also
      produced inhibition of tritium secretion elicited by ES and K+. Dipyridamole
      reduced both the uptake of [3H]NA and [3H]adenosine.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1980290
TI  - The pharmacokinetics and pharmacodynamics of a new thromboxane synthetase
      inhibitor, 6-(1-imidazolylmethyl)-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid
      (DP-1904) in man after repeated oral doses.
AB  - The pharmacokinetics of DP-1904, a new potent and selective thromboxane
      synthetase inhibitor, and its effects on ex-vivo prostanoid formation have been
      studied in groups of Japanese normal male volunteers, who received repeated oral
      doses of 200 mg every 12 h for 4 doses, or 400 mg every 24 h for 2 doses, or 200
      mg every 12 h for 14 doses. The drug was well tolerated by all subjects without
      evidence of adverse reactions. Repeated administration showed no significant
      changes in half-lives, tmax values, cmax values and AUC values. DP-1904 did not
      exhibit time-dependent kinetics. Its plasma levels were lower than the
      quantifiable level (50 ng mL-1) at 12 h after each dose. These data suggest no
      significant accumulation of DP-1904 in normal volunteers. DP-1904 reduced the
      serum thromboxane B2 by about 80% during the medication, the serum concentrations
      returning to about 44, 75 and 20% of the predrug control values at 36 h after the
      last 200 mg doses and 48 h after the last 400 mg dose.

PMID- 1980292
TI  - The influence of density on the gastrointestinal transit of pellets.
AB  - The gastric emptying, intestinal transit and caecum arrival times of 1 mm pellets
      of density 1.5 and 2.8 g cm-3 have been assessed in fed and fasted volunteers by
      means of gamma-scintigraphy. The pellets were prepared by
      extrusion/spheronisation, coated with ethylcellulose and labelled with technetium
      99m. The position of the pellets in the gastro-intestinal tract was followed by a
      double-headed gamma camera to allow detailed information over a period of up to
      10 h. Analysis of variance established that there was a highly significant
      difference in the time for 50% of the pellets to empty from the stomach both in
      fed and fasted states. The 2.8 g cm-3 pellets had an extended resident time in
      both the fed and fasted states. The gastric emptying time was prolonged in the
      fed state. There was no significant difference in intestinal transit time between
      the two formulations nor whether the volunteers were fed or fasted. The caecum
      arrival time was therefore modified only by the gastric emptying time.

PMID- 1980291
TI  - Interspecies pharmacokinetic scaling of some iodinated organic acids.
AB  - We have investigated the possibility of interspecies scaling of relationships
      between the structure and total plasma clearance in a group of nine organic acids
      (iododerivatives of benzoic, phenylacetic and hippuric acids) in rabbits, rats
      and mice. The intercompound comparison established the dependence of total plasma
      clearance predominantly on the molecular structure in all the animals under
      study, but the dependence on drug lipophilicity was also meaningful. For
      interspecies scaling of total plasma clearance, the use of a biological clock
      with an effective renal plasma flow as the unit seemed most suitable and is
      probably connected with the principal role of the kidney in the elimination of
      the compounds under study.

PMID- 1980293
TI  - The interaction of orally administered iron with levodopa and methyldopa therapy.
AB  - The ability of methyldopa and levodopa to interact with both ferrous and ferric
      iron under a variety of conditions likely to be encountered physiologically has
      been examined. Spectrophotometric studies of ferrous sulphate in the presence of
      methyldopa indicate that no complexation occurs below pH2, whilst between pH 4-9,
      a variety of iron-methyldopa complexes is formed. The formation of these
      complexes is fast at high pH (pH 9: t1/2 less than 5 s), whilst the rate slows as
      the pH is lowered (pH 4: t1/2 greater than 30 min). These complexes are
      characteristic of iron-catecholate species, indicating that in the presence of
      methyldopa (and levodopa) ferrous iron undergoes autoxidation to the ferric form.
      The tight binding of ferric iron to methyldopa is predicted to alter the
      biodistribution characteristics of the complex with respect to the unchelated
      components. Furthermore, under the acid conditions of the stomach, redox cycling
      can occur. This will result in both catechol oxidation and production of the
      toxic hydroxyl radical. The findings suggest that care should be exercised when
      simultaneous administration of either methyldopa or levodopa with ferrous
      sulphate is indicated.

PMID- 1980294
TI  - Paracetamol potentiates stress-induced gastric ulceration in rats.
AB  - The effect of paracetamol on gastric ulcers produced by restraint at 4 degrees C
      for 2 h (stress) was studied in rats. Paracetamol treatment s.c. or p.o., with a
      dose as high as 250 mg kg-1, did not produce any haemorrhagic lesions in the
      glandular mucosa. Oral administration with 250 mg kg-1, however, significantly
      reduced the mast cell count in the gastric glandular mucosa and potentiated
      haemorrhagic ulceration but not mast cell degranulation caused by stress. The
      potentiating action was maximum when paracetamol was given between 15 and 30 min
      before stress. Ranitidine, astemizole, dimethylsulphoxide, sucralfate and
      verapamil did not protect against the adverse action of paracetamol on stress
      evoked lesions. This study suggests that paracetamol worsens stress-induced
      stomach ulceration by an action which appears not to be due to histamine release,
      free radical production or intracellular calcium disturbance in the gastric
      mucosa.

PMID- 1980295
TI  - A single injection of a biodegradable microsphere formulation of the ACTH-(4-9)
      analogue ORG 2766 accelerates functional recovery after brain damage.
AB  - The functional recovery from impaired motor activity induced by 6-hydroxydopamine
      lesions in rat nucleus accumbens was accelerated by subcutaneous treatment with
      the ACTH-(4-9) analogue Met/O2/-Glu-His-Phe-D-Lys-Phe (ORG 2766). Treatment was
      effective after daily injections of ORG 2766 dissolved in saline during the first
      6 days following the lesion (ED50: 28.5 ng kg-1 day-1) or after a single
      injection of the peptide in a biodegradable microsphere formulation administered
      after the lesion (ED50: 8.9 ng kg-1 day-1). This study shows that a single
      injection of a microsphere preparation can replace multiple injections with ORG
      2766 in order to facilitate functional recovery after brain damage.

PMID- 1980296
TI  - The in-situ absorption of antipyrine as a measure of intestinal blood flow in
      Fluosol-DA haemodiluted rats.
AB  - The effect of moderate Fluosol-DA haemodilution on intestinal blood flow has been
      investigated in the rat. Antipyrine in-situ intestinal absorption is blood flow
      limited, and did not alter 0.5, 24, 48, or 72 h after haemodilution with 40 mL kg
      1 Fluosol. Thus the intestinal blood flow rate is maintained as part of the
      physiological response to ensure adequate perfusion of the vital organ.

PMID- 1980297
TI  - Effect of phospholipid emulsifiers on physicochemical properties of intravenous
      fat emulsions and/or drug carrier emulsions.
AB  - The physicochemical properties of soy bean oil emulsions stabilized with purified
      egg lecithins (phosphatides) of various concentrations have been examined. The
      zeta potential of the emulsion droplets and the mean particle size of oil
      droplets in 10% (w/w) o/w-type emulsion decreased with increasing emulsifier
      concentration and then levelled off at more than 1.2% (w/w). In rheological
      measurements, at the initial stage, the viscosity of 10% (w/w) o/w-type emulsion
      gradually increased with increasing purified egg lecithin concentration, at the
      next stage, a plateau was reached at about 1.0-1.4% (w/w), and at the final
      stage, the viscosity curve showed a dramatic increase. These results indicate
      that emulsions stabilized by purified egg lecithin at more than 1.2% (w/w) are
      likely to be sufficiently stable.

PMID- 1980298
TI  - The effect of chronic captopril administration on hepatic blood flow of the rat.
AB  - The effect of chronic captopril administration on indocyanine green (ICG)
      clearance and hepatic extraction has been studied in the rat using the intact
      liver for ICG clearance and the isolated perfused liver for ICG extraction. The
      captopril was added to the drinking water to give a calculated daily intake from
      0-45 mg kg-1. Hepatic clearance of ICG was dose related from 16.5 +/- 2.4
      (control) to 7.2 +/- 1.6 mL min-1 kg-1, respectively. The hepatic extraction of
      ICG was not significantly different (37 +/- 6%) from the control value in groups
      on 4 and 45 mg kg-1 daily. Since ICG clearance and extraction are dependent on
      hepatic blood, a change in ICG clearance without a change in the extraction
      reflects a similar change in the hepatic blood flow. This remained unchanged at
      daily captopril intakes of 1 and 4 mg kg-1 and decreased when the daily intake
      was 10 mg kg-1 or higher. If these results in the rat are applicable to man, the
      chronic administration of therapeutic doses of captopril (0.5-2 mg kg-1) will not
      affect the hepatic blood flow.

PMID- 1980299
TI  - Diffusion coefficient in native mucus gel of rat small intestine.
AB  - The diffusion coefficients of [3H] water, urea, benzoic acid, antipyrine,
      aminopyrine, alpha-methyl-glucoside, L-phenylalanine and of hydrogen ions were
      measured at 38 degrees C in native mucus gel from rat small intestine. The
      diffusion in the gel was reduced to 37-53% (for hydrogen ions to 7%) compared
      with buffer solution. In addition, the buffering capacity of the gel retarded the
      permeation of hydrogen ions before a steady state flux was attained. A model
      calculation revealed that in the preparation a gel layer of 80 microns thickness
      represents 23% of the total permeation resistance for substances with high
      epithelial permeability. The aqueous part of the pre-epithelial diffusion
      resistance amounts to 77% of the total resistance.

PMID- 1980300
TI  - Inhibitory action of calcitonin gene-related peptide (CGRP) in the mouse colon.
AB  - The effect and mechanism of action of calcitonin gene-related peptide (CGRP) have
      been investigated on the mouse distal colon. CGRP caused a concentration
      dependent relaxation which was not blocked by classical pharmacological
      antagonists. The response pattern was characterized by a relatively rapid onset
      and long sustained duration. The results suggest that CGRP itself may contribute
      to regulating the muscular tone of the mouse colon.

PMID- 1980301
TI  - Antinociceptive and anti-inflammatory activity of a novel quipazine derivative
      (AAL-13): a selective inhibitor of 5-hydroxytryptamine reuptake.
AB  - The anti-inflammatory and antinociceptive activities of a novel quipazine
      derivative 2(4-(3-chloropropyl)piperazinyl) quinoline (AAL-13), a selective
      inhibitor of 5-hydroxytryptamine (5-HT) reuptake, has been examined. Anti
      inflammatory activity was assessed by mesuring the inhibition of a cotton pellet
      granuloma and of carrageenan-induced paw oedema in rats, and of cantharidin
      induced topical inflammation in the mouse ear. Antinociceptive activity was
      studied by using the modified Randall-Selitto method. Indomethacin was used as a
      reference. AAL-13 slightly inhibited granuloma formation (13%, P less than 0.02)
      at 100 mg kg-1 day-1 for 7 days, whereas half that dose had no significant
      effect. There was significant inhibition of carrageenan-induced rat paw oedema
      (35%, P less than 0.05 and 103%, P less than 0.001) 3 h after single doses of AAL
      13 (50 and 100 mg kg-1 p.o., respectively). Three hours after i.p. injection, the
      oedema inhibition was 58% (P less than 0.05) and 86% (P less than 0.001) for
      doses of 25 and 50 mg kg-1, respectively. In comparison, indomethacin (3, 6 and
      12 mg kg-1 p.o.) inhibited oedema by 59% (P less than 0.02), 65% (P less than
      0.01) and 63% (P less than 0.02), respectively. Intraperitoneally, only the 12 mg
      kg-1 dose produced significant inhibition (82%, 3 h after carrageenan injection,
      P less than 0.05). AAL-13 (1.5 mg/ear) had a significant anti-inflammatory effect
      on the mouse ear (52%, inhibition, P less than 0.05), while indomethacin (3
      mg/ear) gave 43% inhibition (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1980302
TI  - Cyclosporin A treatment enhances angiotensin converting enzyme activity in lung
      and serum of rats.
AB  - Nephrotoxicity and arterial hypertension are the most common side effects of
      treatment with cyclosporin A (CSA). Its effects on angiotensin converting enzyme
      (ACE) activity in the renal cortex, lung and serum of nephrotoxic rats have been
      investigated. Wistar rats were treated with CSA (20 mg kg-1 day-1 i.p.) or
      vehicle (olive oil containing 10% ethanol) for 14 days. On day 15, the rats were
      killed and ACE activity determined by radiometric assay using [3H]hippuryl-glycyl
      glycine as substrate. CSA treatment resulted in a decrease in creatinine
      clearance, urine flow and body weight and a significant increase in serum and
      lung ACE activities (436 +/- 9 vs 391 +/- 7 nmol mL-1 min-1, P less than 0.001;
      184 +/- 8 vs 142 +/- 10 nmol mg-1 min-1 P less than 0.01, respectively). In
      contrast, renal cortex ACE activity was reduced in the CSA-treated rats (0.35 +/-
      0.02 vs 0.51 +/- 0.02 nmol mg-1 min-1, P less than 0.01). ACE activities in the
      renal cortex and serum were not affected by treatment with gentamicin (80 mg kg-1
      day-1) for 11 days. In rats treated simultaneously with CSA and captopril (50 mg
      kg-1 day-1) ACE activity in the serum, lung and renal cortex was inhibited by 95,
      93 and 92%, respectively. These changes in ACE activity were associated with a
      decreased systolic blood pressure in the rats receiving CSA and captopril.
      Therefore, ACE activity in the serum and lung of CSA-treated rats was increased,
      while its activity in the renal cortex was reduced.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1980303
TI  - Mean residence time: an invalid estimation method.

PMID- 1980304
TI  - British Pharmaceutical Conference 1990. Science proceedings: 127th meeting.
      Cardiff, September 10-13, 1990.

PMID- 1980305
TI  - [Studies on the synthesis of condensed pyridazine derivatives. I. Synthesis and
      benzodiazepine receptor binding studies of 2-substituted-4,4a,5,6
      tetrahydrobenzo[h]cinnolin-3(2H)-ones and related compounds].
AB  - A series of 2-substituted-4,4a,5,6-tetrahydrobenzo[h]cinnolin-3(2H)-ones and
      related compounds were synthesized and tested for their ability to displace
      [3H]diazepam from rat brain membranes. Among them, compounds bearing 4
      methoxyphenyl, 4-chlorophenyl, or 4-methylphenyl group at the position-2 were
      found to have high affinity to the benzodiazepine receptor. 2-(4-Methoxyphenyl)-9
      methyl- and 2-(4-methoxyphenyl)-9-methoxy-4,4a,5,6-tetrahydrobenzo[h]cinnolin-
      3(2H)-ones (8b-14 and 8b-15, respectively) showed a potent affinity comparable to
      that of diazepam. These results suggest that a topographical planarity or
      pseudoplanarity of these molecules is essential for high affinity to the
      benzodiazepine receptor. The structure-activity relationships are discussed.

PMID- 1980306
TI  - [Studies on the synthesis of condensed pyridazine derivatives. II. Synthesis and
      anxiolytic activities of 2-aryl-4,4a,5,6-tetrahydropyridazino[4,3-c]quinolin
      3(2H)-ones, 2-aryl-4a,5-dihydro-2H-(1)benzothiopyrano[4,3-c]pyridazin-3(4H)-ones,
      and related compounds].
AB  - A series of 2-aryl-4,4a,5,6-tetrahydropyridazino[4,3-c]quinolin-3(2H)- ones, 2
      aryl-4a,5-dihydro-2H-(1)benzothiopyrano[4,3-c]pyridazin-3( 4H)-ones, and related
      compounds were synthesized and tested for their ability to displace [3H]diazepam
      from rat brain membranes in vitro, and to prevent bicuculline-induced convulsions
      in mice in vivo. Among them, 2-(4-chlorophenyl)-4a,5-dihydro-2H
      (1)benzothiopyrano[4,3-c]pyr idazin-3(4H)- one (16b) showed remarkable activities
      both in vitro (Ki 48 nM) and in vivo (ED50 12.4 mg/kg, p.o.). The trans sulfoxide
      (19a) of 16b exhibited anxioselective pharmacological activities. Compound 19a
      was equipotent with diazepam in the anticonflict assay (Vogel type, rat, MED 10
      mg/kg, p.o.) while exhibiting reduced muscle relaxation (rotarod test) and
      narcotic potentiation. The structure-activity relationships are discussed.

PMID- 1980307
TI  - Liquid chromatographic assay and pharmacokinetics of halazepam and its metabolite
      in humans.
AB  - A reversed-phase high-performance liquid chromatographic method is described for
      simultaneous quantification of halazepam and its major active metabolite,
      nordiazepam, in plasma. The method uses a solid-phase extraction procedure to
      prepare plasma samples. After extraction, the methanolic extract is evaporated,
      and the residue is then reconstituted in a small volume of mobile phase (a 40:60,
      v/v, mixture of 0.02 M phosphate buffer, pH 4.0, and methanol) and
      chromatographed. The total chromatography time for a single sample is
      approximately 10 min. A sensitivity of 1 ng/mL for halazepam and nordiazepam is
      attained when 1 mL of plasma is extracted. Analytical recovery of halazepam and
      nordiazepam added to the plasma ranged from 89 to 96%. The maximum within-day and
      day-to-day coefficients of variation for each compound at the concentration range
      of 2 to 100 ng/mL were 8.7 and 10.3%, respectively. Suitability of the method was
      assessed in a preliminary pharmacokinetic study in which three subjects were
      given a single 20-mg oral dose of halazepam following an overnight fast. It
      appeared from our kinetic analysis that halazepam is a drug with a fairly rapid
      absorption phase that is followed by a slow elimination phase. Mean oral plasma
      clearance of halazepam was 24 L/h. The mean apparent elimination half-life of
      nordiazepam (45.22 h) is considerably longer than that of halazepam (21.15 h).

PMID- 1980308
TI  - Report of the workshop on in vitro and in vivo testing and correlation for oral
      controlled/modified-release dosage forms.

PMID- 1980309
TI  - Your CE topic (no. 52). Therapeutic inhalation aerosols in the treatment of
      asthma.

PMID- 1980310
TI  - Meta-analysis of sulfasalazine in ankylosing spondylitis.
AB  - At present there is no widely accepted therapy for ankylosing spondylitis (AS), a
      progressive debilitating disease. The effectiveness of sulfasalazine in AS still
      lacks strong evidence, as well, the magnitude of its benefit is unknown. A meta
      analysis was carried out to assess the effectiveness of sulfasalazine in AS. A
      search of the literature was done using Medline, Index Medicus, the reference
      lists of articles located and contacting content experts to reveal unpublished
      studies. Five randomized controlled trials (RCT) comparing sulfasalazine to
      placebo were located and assessed methodologically. The methodologic quality of
      all 5 RCT was considered satisfactory and consequently these studies were
      included in the meta-analysis. The pooled estimate of clinical benefit (and its
      95% confidence interval) favoring sulfasalazine, over and above that observed in
      the placebo group was as follows: Duration of morning stiffness -28.2% (-54.6 to 
      1.8%); severity of morning stiffness -30.6% (-52.5 to -8.7%); severity of pain 
      26.7% (-44.3 to -9.1%); general well being -7.1% (-24.3 to 10.0%); erythrocyte
      sedimentation rate -9.2% (-24.8 to 6.4%); and IgA -11.7% (-18.8 to -4.7%).
      Adverse effects, mostly mild, were more frequently observed in the sulfasalazine
      group (odds ratio [OR] = 1.5746, p = 0.1082). The occurrence of dropouts (OR =
      1.1554, p = 0.6119) was similar in both groups. Sulfasalazine is a safe and
      effective drug in the short term treatment of AS.

PMID- 1980311
TI  - Macroscopic and microscopic gut lesions in seronegative spondyloarthropathies.
AB  - A retrospective study by ileocolonoscopy and multiple biopsies was performed on
      96 patients with seronegative spondylarthropathy, 17 patients with osteoarthritis
      (OA) and 19 patients with chronic abdominal discomfort. Under these conditions,
      inflammatory gut lesions were detected in 66.7% of the patients with
      spondyloarthropathy, 12.5% with OA and 15.8% with chronic abdominal discomfort.
      In 10 patients treated by sulfasalazine (Salazopyrine), pathologic lesions
      disappeared simultaneously with an improvement of the rheumatic conditions.
      comparison between patients treated and untreated with nonsteroidal inflammatory
      drugs (NSAID) demonstrated that NSAID did not enter into the etiopathology of the
      intestinal lesions. Our study therefore confirms the high incidence of
      inflammatory gut lesions among patients with spondylarthropathy which seems not
      to be related to NSAID therapy.

PMID- 1980312
TI  - Challenging the pyramid--a new look at therapeutic approaches for rheumatoid
      arthritis. March 9-10, 1990, Miami, Florida. Proceedings.

PMID- 1980313
TI  - Challenging the pyramid. A new look at therapeutic approaches for rheumatoid
      arthritis. Earlier intervention with second line therapies.
AB  - It is clear that nonsteroidal antiinflammatory drugs (NSAID) may help control the
      pain and swelling of rheumatoid arthritis (RA) but do not retard joint
      destruction. Similarly, prednisone is effective in controlling pain and swelling
      but it cannot be established that it prevents or delays joint damage. When added
      to NSAID and prednisone, second line drugs (DMARD) have the potential to provide
      additional control of synovitis and improve function. Each second line drug has a
      unique tolerability and safety profile. Patients who are more likely to have a
      progressive course should be evaluated for second line drugs rather than risk
      irreversible damage.

PMID- 1980314
TI  - Combination therapy of rheumatoid arthritis--rationale and overview.
AB  - Currently available therapeutic agents for the treatment of rheumatoid arthritis
      are unsatisfactory for many patients, due either to inefficacy, loss of
      effectiveness with time, or toxicity. One approach is to study drugs in
      combination, at lower than usual dosages of each, in order to achieve greater
      efficacy with fewer adverse reactions. To aid in this review of published trials,
      the various combinations have been arbitrarily divided into combinations of
      cytotoxic (antiproliferative) drugs with each other, and combinations of
      noncytotoxic drugs. Of the noncytotoxic combinations, intramuscular gold with D
      penicillamine appeared to offer the best results without increased side effects
      when compared to each one used alone. The most promising cytotoxic combination
      was methotrexate with azathioprine.

PMID- 1980315
TI  - Challenging the pyramid. A new look at terapeutic approaches for rheumatoid
      arthritis. Patient selection.
AB  - The goals of therapy for rheumatoid arthritis (RA) address alleviation of pain;
      prevention of joint destruction, deformity, and disability; and maintenance of
      life style. Disease modifying antirheumatic drugs (DMARD) are among the most
      important agents to accomplish these goals, but guidelines for their introduction
      into management have not been clearly established. In 1986 a survey regarding
      DMARD usage was conducted among 1057 specialists in arthritis. The key criteria
      used in patient selection were progressive pattern of disease, persistent
      synovitis, and the degree of swollen joints. Eighty-four percent of respondents
      waited 3 to 6 months from the time of initial diagnosis of RA before starting
      DMARD. Parenteral gold was then the most preferred DMARD.

PMID- 1980316
TI  - Use of LeuM1 monoclonal antibody for the diagnosis of Hodgkin's disease.
AB  - Monoclonal antibody to LeuM1, a granulocyte-related differentiation antigen,
      represents a highly effective reagent for detection of diagnostic "Reed
      Sternberg" cells and variants in paraffin-embedded tissues of Hodgkin's disease.
      The "Reed Sternberg" cell in all the cases of Hodgkin's disease except lymphocyte
      predominance variety revealed positive intracytoplasmic/paranuclear granular
      staining with LeuM1 marker. The R-S cells in lymphocyte predominance variety
      contain probably sialylated LeuM1 antigen. All the cases of non-Hodgkin's
      lymphoma and reactive lymphadenitis showed no staining with LeuM1 monoclonal
      antibody. Therefore this antibody represents a potentially helpful diagnostic
      discriminant in the assessment of Hodgkin's disease and its distinction from non
      Hodgkin's lymphomas and morphologically similar reactive lymphoid lesions.

PMID- 1980317
TI  - [Use of vecuronium bromide for anesthesia for renal transplantation].
AB  - We used vecuronium on 7 patients for renal transplants and recorded the muscle
      relaxant effect using an Anesthesia and Brain Monitor; we also compared them with
      patients with normal renal function. Results show that there were no significant
      differences between renal transplant patients and patients with normal renal
      functions in regard to the time of appearance of effect, duration of effect and
      recovery rate but the effect was somewhat prolonged in the renal transplant
      patients. Therefore, although vecuronium is said to be a muscle relaxant with
      little renal dependency, and it is used on renal transplant patients with renal
      insufficiency, the possibility of a prolonged effect must be considered. It is
      important to monitor continuously by a muscle relaxant monitor, grasp adequately
      the conditions of muscle relaxation, and observe carefully the postoperative
      respiratory conditions.

PMID- 1980318
TI  - [Rapid detection and identification of mycobacterial DNA by PCR].
AB  - We have developed a highly sensitive and rapid PCR assay for detection and
      identification of mycobacterial species. Two sets of PCR primers were prepared;
      one was for the 19 kDa antigen gene and the other for the dna J gene. The PCR for
      19 kDa antigen gene was found to be specific to the M. tuberculosis complex; M.
      tuberculosis, M. bovis and M. africanum. On the other hand, the PCR for the dna J
      gene was able to detect a broad spectrum of mycobacterial species including M.
      tuberculosis, M. avium, M. intracellulare and M. kansasii. The sensitivity of PCR
      was similar to that of the culture method for precultured M. tuberculosis whereas
      PCR was much more sensitive than the culture for clinical samples. The procedure
      of decontamination by sodium hydroxide for clinical samples could reduce the
      viability of M. tuberculosis while it did not affect mycobacterial DNA. The
      nucleotide sequence homologies among major mycobacteria were also determined
      following PCR for the dna J gene. This allowed us to make restriction maps for
      each mycobacterium. We have demonstrated that the PCR-RFLP for the dna J gene
      will be a useful laboratory test for rapid identification of tuberculous and
      nontuberculous mycobacterial species.

PMID- 1980319
TI  - [Heterogeneity of restriction enzyme cleavage pattern of molluscum contagiosum
      virus DNA].
AB  - The total NDAs obtained from a clinically atypical molluscum contagiosum (MC)
      found in a 47-year-old, male immunosuppressed renal allograft recipient and from
      seven MC of usual infantile cases were digested with BamHI restriction enzyme and
      analyzed by agarose gel electrophoresis. Three different cleavage patterns were
      observed and tentatively named MCV-a, -b and -c. All the infantile cases were
      infected by either MCV-a or MCV-b, both of which showed similar cleavage
      patterns. In contrast, the immunosuppressed patient was infected by MCV-c, whose
      cleavage pattern was quite different from those of MCV-a and -b. These results
      clarified the heterogeneity of MCV in Japanese patients with MC and implied the
      correlation between MCV types and clinical features of MC.

PMID- 1980320
TI  - Takayasu's arteritis with heart failure due to atherosclerosis.
AB  - An autopsy case of an elderly man with Takayasu's arteritis and atherosclerosis
      is presented. Ischemic signs and symptoms including anginal attack were
      aggravated with activity of arteritis despite administration of prednisolone
      throughout the entire course. The autopsy revealed severe atherosclerosis over
      the aorta and its branches, and arteritis in the fibrotic stage in localized
      area. Vessels of vital organs including heart and kidneys, did not show
      Takayasu's arteritis but were atherosclerotic. This case highlights the numerous
      problems encountered in the treatment of elderly patients with vasculitis such as
      Takayasu's arteritis.

PMID- 1980321
TI  - A case of malignant pheochromocytoma treated with 131I-metaiodobenzylguanidine
      and alpha-methyl-p-tyrosine.
AB  - A 47-year-old man had surgery for paraaortic paraganglioma in 1980 and 1985. In
      1987, his urinary excretion of catecholamines and metabolites was extremely high.
      Scintigraphy with 131I-metaiodobenzylguanidine (MIBG) showed multiple bone and
      liver metastases. He was treated twice with infusions of 3.7 GBq of 131I-MIBG.
      After the first treatment, he had transient hypertension and pain in the back and
      right leg. Subsequent 131I-MIBG scintigraphy showed that the number of metastatic
      tumors had decreased. The second treatment was less effective. Excess
      catecholamines were treated with alpha-methyl-p-tyrosine (MPT), a catecholamine
      synthesis inhibitor, at doses between 250 and 2000 mg/day, which significantly
      decreased urinary NE excretion. This is the first case treated with 131I-MIBG in
      Japan.

PMID- 1980323
TI  - [Physiological control mechanism of gastrointestinal motility].

PMID- 1980324
TI  - [Clinico-bacteriological studies on the etiology of bacterial prostatitis. II.
      Virulence factors of E. coli in bacterial prostatitis].
AB  - The virulence factors of E. coli in bacterial prostatitis were studied using 59
      E. coli isolated from uncomplicated prostatitis. O-antigens of prostatitis
      derived E. coli belonged to some specific serotypes such as 0-4, 6, 18, 22 and
      the haemolysin production was positive in 64.4%. With regard to the fimbriae, the
      majority of the strains had type 1 fimbriae (81.4%). Mannose resistant (MR)
      fimbriae were also positive in 59.3% and both type 1 and MR fimbriae were
      positive in 55.9%. Among MR strains, P-fimbriated and S-fimbriated strains were
      present in 25.7% and 28.6%, respectively, indicating that these two MR fimbriae
      were not always specific for the prostatitis-derived E. coli. Although the
      specific adhesion of E. coli onto the human prostatic epithelium mediated by MR
      fimbriae was equivocal, that mediated by type 1 fimbriae was observed clearly.
      Therefore, type 1 fimbriae was thought to be one of the most significant
      virulence factors in the pathogenesis of prostatitis caused by E. coli.

PMID- 1980322
TI  - The treatment of pheochromocytoma associated with pseudo-obstruction and
      perforation of the colon, hepatic failure, and DIC.
AB  - The case of a 59-year-old man with paralytic ileus (pseudo-obstruction)
      associated with pheochromocytoma is reviewed. Paralytic ileus is believed to have
      been the result of overstimulation of alpha and beta receptors on the intestine
      by catecholamines. Phentolamine, bunazocin, propranolol, bethanechol and
      midaglizole in single administrations or in combination were administered.
      Phentolamine infusion clearly relieved the symptom, but ileus recurred, and the
      patient died of respiratory failure, liver dysfunction and disseminated
      intravascular coagulation syndrome. The significant role of catecholamines in
      causing these symptoms is discussed, and the management of this relatively rare
      complication is reviewed.

PMID- 1980325
TI  - [Hyperbaric oxygen and antianginal agents: experimental and clinical aspects of
      their interaction].

PMID- 1980326
TI  - [Comment on combined use of beta-adrenergic stimulants and beta-adrenoblockers].

PMID- 1980327
TI  - [The significance of disorders of neurohumoral regulation in the pathogenesis of
      acute cholecystitis].

PMID- 1980328
TI  - [Abuse potential of benzodiazepines. Sensible use means continuous follow-up].

PMID- 1980329
TI  - GBR-12909 and fluspirilene potently inhibited binding of [3H] (+)3-PPP to sigma
      receptors in rat brain.
AB  - Fluspirilene and GBR-12909, two compounds structurally similar to BMY-14802 and
      haloperidol, were assessed for their ability to interact with sigma receptors.
      Fluspirilene, an antipsychotic agent that interacts potently with dopamine
      receptors, inhibited the binding of [3H]-(+) 3-PPP (IC50 = 380 nM) more potently
      than rimcazole, a putative sigma antagonist that was tested clinically for
      antipsychotic activity. GBR-12909, a potent dopamine uptake blocker, also
      inhibited the binding of [3H]-(+) 3-PPP with an IC50 of 48 nM. However, other
      compounds that block the re-uptake of catecholamines, such as nomifensine,
      desipramine, imipramine, xylamine, benztropine and cocaine, were much weaker than
      GBR-12909 as sigma ligands. Thus, GBR-12909 and fluspirilene, compounds
      structurally similar to BMY-14802, are potent sigma ligands.

PMID- 1980330
TI  - Alpha adrenergic drugs inhibit [3H]-QNB binding to muscarinic receptors of rat
      heart, brain and parotid gland membranes.
AB  - Alpha adrenergic agonists and antagonists as clonidine, guanfacine, yohimbine,
      phenylephrine and prazosin inhibited the [3H]-QNB binding to rat brain cortex
      muscarinic acetylcholine receptor (mAChR, M-1 subtype), heart (M-2 subtype) and
      parotid gland homogenate (M-3 subtype) in a dose-dependent competitive fashion.
      Ki values were between 10(-6) and 10(-3) M. Hill coefficients were about 1. No
      correlation was found between mAChR inhibiting capacity of these drugs and their
      activity on alpha adrenergic receptors. In contrast, other transmitters, as
      dopamine, GABA, glutamic acid, histamine, serotonin, isoproterenol and platelet
      activating factor (PAF) did not affect the QNB binding.

PMID- 1980331
TI  - Somatostatin content and binding in small intestinal mucosa from fed, fasted, and
      refed rabbits.
AB  - The present study is an investigation of the effects of 12- to 96-hours'
      starvation and 96-hours' starvation plus 48-hours' refeeding on both somatostatin
      like immunoreactivity (SLI) and cytosolic somatostatin binding sites in rabbit
      small intestinal mucosa. The SLI concentration increased after 24 h in duodenal
      and jejunal mucosa, but not in ileal mucosa, and reached its highest value after
      96 h of fasting. The number of specific high and low-affinity somatostatin
      binding sites, but not their affinity, decreased with the duration of fasting in
      the same gut segments, refeeding of fasted animals resulted in a return to normal
      control values for small intestine mucosal SLI and somatostatin binding.

PMID- 1980332
TI  - [Effects of chorionic gonadotropin (hCG) therapy on the immune system].
AB  - Humoral and cellular immunologic parameters were evaluated in 13 prepuberal
      cryptorchid boys before, during and 3 months after hCG therapy. Before treatment,
      all the immunologic parameters were normal except for a higher percentage of T
      suppressor-cytotoxic cells (CD8+). During therapy, the percentage of CD8+ cells
      and lymphocyte response to ConA significantly decreased, and returned to the
      control level after hCG withdrawal. The possible effects of long-term hCG
      treatment on the immune system remains to be determined.

PMID- 1980333
TI  - [Medical treatment of acromegaly with dopaminergic agents].
AB  - The medical treatment of acromegaly with dopaminergic drugs has its
      physiopathological premise in the observation that agents capable of stimulating
      dopaminergic receptors directly are capable of determining GH secretion
      inhibition in a large percentage of acromegalic patients. Chronic administration
      of 5-20 mg/die of bromocryptin, long acting dopaminergic agonist, leads to a
      stable reduction in the levels of GH and somatomedin C (SmC) in about 50% of
      patients. However, these are only normalised in 20%. Treatment induces marked
      improvement in the clinical and metabolic changes typical of acromegalic disease.
      The therapeutic effect of dopaminergics may be maintained for periods of
      treatment lasting years but upon suspension of treatment pH levels return quickly
      to pretreatment levels. The antitumoral effect of the dopaminergic frequently
      encountered in prolactinomas is a rarer event in acromegaly and occurs more
      readily in patients with mixed secreting GH and PRL tumours than in pure GH.
      Currently octractide, a long lasting somatostatin analogue, is the most effective
      drug in the medical treatment of acromegaly; however the dopaminergic agonists
      remain a valid alternative.

PMID- 1980334
TI  - A new class of S sequences defined by a pollen recessive self-incompatibility
      allele of Brassica oleracea.
AB  - Self-incompatibility in Brassica oleracea is controlled by a single genetic locus
      (the S locus) with nearly 50 different alleles. In this paper, we report the
      characterization of the S2 allele, a pollen recessive self-incompatibility allele
      that exhibits weak DNA homology to the other previously sequenced S locus
      glycoprotein genes (SLG-6, -13, -14, -22 from alleles S6, S13, S14 and S22,
      respectively). Stigma cDNA clones with sequence homology to SLG-13 were isolated
      from two different S2 homozygous strains belonging to two different B. oleracea
      cultivars, var. alboglabra (Chinese kale) and var. italica (broccoli). The two S2
      cDNA sequences are 90% homologous to each other, but only 70% homologous to SLG
      13. Using the Chinese kale S2 genetic background, we demonstrate that the
      isolated alboglabra cDNA sequence is a transcript from a gene, designated SLG-2A
      that resides at the S locus, and propose that it is a putative determinant of S2
      allelic specificity. Among the estimated 10-15 genomic copies of SLG-related
      genes detected in the S2 genome, we cloned and characterized the SLG-2A gene and
      another closely related and genetically linked gene copy, SLG-2B. A complete open
      reading frame that is 94% homologous to SLG-2A is located within SLG-2B. The
      existence of this intact duplicated S gene raises the possibility that SLG-2B may
      also be involved in the functioning of self-incompatibility in Brassica oleracea.

PMID- 1980335
TI  - Restriction fragment length polymorphism analysis of somatic hybrids between
      Lycopersicon esculentum and irradiated L. peruvianum: evidence for limited donor
      genome elimination and extensive chromosome rearrangements.
AB  - The genome composition of asymmetric somatic hybrids, obtained by fusion of leaf
      protoplasts from Lycopersicon esculentum and gamma-irradiated leaf protoplasts
      from L. peruvianum, was characterised by Southern blot analysis using 29
      restriction fragment length polymorphism markers. Eight "low dose hybrids" and
      seven "high dose hybrids" (irradiation dose 50 Gray and 300 Gray, respectively)
      were analysed. By densitometric scanning of the autoradiographs, the number of
      alleles for each locus of the component species was established. In general,
      elimination of alleles from the irradiated L. peruvianum donor genome was limited
      and ranged from 17%-69%. Three L. peruvianum loci, located on chromosomes 2, 4
      and 7, were present in all asymmetric hybrids, suggesting linkage to the
      regeneration capacity trait which was used in selecting them. The loss of donor
      genome was dose-dependent. Low dose hybrids contained more alleles, loci and
      complete chromosomes from L. peruvianum than high dose hybrids, whereas the high
      dose hybrids contained more incomplete chromosomes. In most hybrids some L.
      esculentum alleles were lost. The possible implications of these results for the
      use of asymmetric hybrids in plant breeding are discussed.

PMID- 1980336
TI  - Mapping of insertion element IS30 in the Escherichia coli K12 chromosome.
AB  - We identified seven phage clones containing the insertion element IS30 in a
      lambda phage library mini-set, which includes 476 clones carrying chromosomal
      segments that cover almost the entire chromosome of Escherichia coli K12 W3110
      (Kohara et al. 1987). We could assign locations and orientations to four copies
      of IS30 (named is30A to is30D) on the W3110 chromosome by restriction analysis of
      phage DNAs containing them. These IS30s were present at the same locations in
      chromosomes of both W3110 and another E. coli K12 strain JE5519, and thus are
      assumed to be present in other E. coli K12 derivatives, including early isolates.
      Among the IS30 copies found, one (is30B) contained a large deletion and possessed
      only a 181 bp stretch of the right terminal region of IS30.

PMID- 1980337
TI  - Structural variability in the genome of the Thermoproteus tenax virus TTV1.
AB  - Six variants of the TTV1 genome, including the primary isolate, have been
      characterized. DNA sequence comparison of 'wild-type' virus (WT) and one of the
      variants (VT3) showed that differences are due to insertions and deletions that
      were confined to contiguous portions of two distinct ClaI fragments. Seven
      similar short DNA sequences (30-102 bp) were involved in the variation. The
      deletions and insertions of these short DNA sequences occurred in every case
      adjacent to the 8 bp consensus sequence 5'-ACXCCTAC-3' which formed the 5' flank
      of the segments involved.

PMID- 1980338
TI  - Receptor-like oncogenes: functional analysis through novel experimental
      approaches.
AB  - A growing proportion of the known protooncogenes encode putative receptors for
      growth/differentiation factors. The detection and identification of the
      hypothetical ligands of these presumed receptors, and the elucidation of their
      biological roles constitute a new biochemical challenge. Employing the neu
      protooncogene, here three experimental approaches to these problems are
      described. Stimulatory anti-receptor antibodies appear to mimic the action of the
      presumptive ligand of the neu receptor, and also lead to the conclusion that the
      oncogenic receptor, unlike the normal p185neu, is functionally equivalent to a
      ligand-stimulated receptor. Second, an experimental strategy was developed for
      the detection of the neu ligand. Employing this approach a candidate ligand was
      detected in the growth medium of certain oncogene-transformed fibroblasts.
      Thirdly, engineered chimeras of the neu gene and the gene for the EGF-receptor
      enabled construction of a neu receptor that is responsive to a heterologous
      ligand. Combinely, these approaches may provide a detailed biological picture of
      the action of the putative ligand, and may be generally applicable in the study
      of other receptor-like oncogenic proteins.

PMID- 1980339
TI  - Contribution of CR3, CD11b/CD18 to cytolysis by human NK cells.
AB  - The complement receptor CR3 molecule functions in direct intercellular contacts
      mediated by its beta chain, CD18. Similarly to the Fc receptor (CD16), CR3 is a
      marker of human natural killer cells. We have shown that opsonization of NK
      targets with iC3b leads to their increased lytic sensitivity. Opsonization could
      be achieved by incubating certain B and T cell lines in human serum. The
      expression of CR2 was a prerequisite for C3 fragment fixation. The CR2 negative
      cell line, P3HR1 could be opsonized by incubation in human serum when induced to
      express the EBV envelope glycoprotein gp350. C3b or iC3b could also be deposited
      artificially on cell surfaces by chemical coupling to surface reactive
      antibodies. Similarly to the function of macrophages and monocytes, contact with
      opsonized targets exclusively through the iC3b binding site of CR3 did not seem
      to trigger NK function. We attempted to clarify the functional role of other CR3
      ligands. The beta chain of the molecule, CD18, was essential to the NK effect.
      The NK targets did not seem to interact with the beta-glucan binding epitope on
      the alpha chain of CR3, CD11b. On the other hand, the cytolytic function could be
      enhanced through this epitope with the appropriate ligand.

PMID- 1980341
TI  - Chemical dependency and prescription drugs.

PMID- 1980340
TI  - Lymphocyte interacting adhesion molecules on brain microvascular cells.

PMID- 1980342
TI  - Distribution and rearrangements of alleles of c-Ha-ras-1 protooncogene and their
      correlation with the development of lung, ovarian and thyroid cancers.
AB  - The protooncogene c-Ha-ras-1 locus in 84 cancer patients was examined for allelic
      restriction fragment length polymorphism. The distribution of four common c-Ha
      ras-1 alleles (a1, a2, a3 and a4) in lung, ovarian and thyroid cancer patients
      was analyzed. In approximately half (8 out of 15) of lung and ovarian carcinomas
      possessing the a4 allele, alterations of the c-Ha-ras-1 locus (deletion of allele
      with the shorter fragment length, amplification of a4 allele, change of allele
      fragment length) were detected as compared to 2 cases of rearrangement out of 40
      tumors lacking the a4 allele. An increased a4 allele frequency was found in
      individuals with lung and ovarian tumors as compared to controls presented in
      literary data and thyroid cancer patients. On the other hand, homozygosity for
      the a2 locus resulting from the deletion of another allele, and increased a2
      allele frequency in thyroid cancer patients were observed. Thus the a4 and a2
      alleles of c-Ha-ras-1 may perhaps be viewed as genetic markers of predisposition
      to lung, ovarian and thyroid cancer, respectively, in combination with other
      clinical parameters.

PMID- 1980343
TI  - [Mollaret benign recurrent aseptic meningitis. Case report, results of
      cerebrospinal fluid cytology and review of the literature].
AB  - Mollaret's recurrent aseptic meningitis is a rare disease of unknown etiology and
      excellent prognosis, characterized by short attacks of meningeal irritation,
      fever and pleocytosis with first polymorphonuclear, then mononuclear
      predominance. A case is reported, in which the characteristic so-called
      endothelial cells in the CSF were identified as monocytes with immunocytochemic
      methods. The remaining fraction of CSF cells mainly consisted of T-lymphocytes
      with a majority of CD4 positive cells and an increased portion of CD38 positive
      cells. Between attacks, patients are asymptomatic. The course is self-limiting.
      Specific treatment is unknown.

PMID- 1980346
TI  - Peripubertal treatment with N-methyl-D-aspartic acid or neonatally with
      monosodium glutamate accelerates sexual maturation in female rats, an effect
      reversed by MK-801.
AB  - Recent reports from several laboratories have implicated the excitatory
      neurotransmitter glutamate as a component in the neural regulation of sexual
      maturation. In the rat we have previously proposed that a hypothalamic opioid
      restraint mechanism may ultimately be overridden by maturation of an excitatory
      drive, culminating in first ovulation. We have now investigated whether glutamate
      may be the excitatory factor. Treatment of immature female rats with single,
      daily injections of two N-methyl-D-aspartate (NMDA) antagonists--dextrorphan (18
      mg/kg) and MK-801 (0.1 mg/kg)--beginning on the 27th postnatal day, significantly
      delayed the timing of vaginal opening (VO). Interestingly, treated rats reached
      VO in spite of continued antagonist treatment. The antagonist effect was reversed
      by preinjection of NMDA, suggesting that endogenous glutamate exerts its effect
      via an NMDA-subtype glutamate receptor. Injection of NMDA alone (15 mg/kg; once
      daily) produced a striking synchronization of VO such that all treated rats
      showed VO over a 24-hour period compared to a normal distribution of several days
      for control rats. In a model of first ovulation, i.e., rats induced to ovulate by
      pregnant mare serum, MK-801 (1 mg/kg) arrested treated rats at proestrus. This
      was readily reversible after discontinuing injections. A lower dose of MK-801
      (0.1 mg/kg/day) was ineffective in delaying ovulation. In a second series of
      experiments we studied the consequences of a neonatal hypothalamic lesion which
      destroys glutamate-sensitive neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1980345
TI  - Hydrocortisone regulates arylsulfatase A (cerebroside-3-sulfate-3-sulfohydrolase)
      by decreasing the quantity of the enzyme in cultures of cells dissociated from
      embryonic mouse cerebra.
AB  - Previous work from our laboratory (Biochem. J. 219:689-697 (1984] had shown that
      hydrocortisone stimulated the net accumulation of the myelin-specific sulfolipid
      in cultures of cells dissociated from embryonic mouse cerebra. This accumulation
      caused by hydrocortisone was shown to be due to a decrease of sulfolipid
      degradation by arylsulfatase A (ASA) and not due to a stimulation of its
      synthesis by a sulfotransferase. Both ASA activity and the turnover of sulfolipid
      were decreased by hydrocortisone to 60-62% of untreated cells. In current work
      the same decrease in enzyme activity was obtained and enzyme linked immunosorbent
      assays demonstrate that hydrocortisone decreased the number of ASA protein
      molecules to 61% of untreated cells [(-)hydrocortisone: 0.31 +/- 0.06 ng
      ASA/microgram protein; (+)hydrocortisone: 0.18 +/- 0.04 ng ASA/microgram
      protein]. This decrease in the number of ASA molecules correlates well with the
      decrease in both the enzyme activity and the sulfolipid turnover, which suggests
      that the major mode of inhibition of ASA activity by hydrocortisone involves a
      decrease in the concentration of ASA in the cells rather than some other
      mechanism of inhibition.

PMID- 1980344
TI  - Effect of age and monosodium-L-glutamate (MSG) treatment on neurotransmitter
      content in brain regions from male Fischer-344 rats.
AB  - Peripheral administration of monosodium-L-glutamate (MSG) has been found to be
      neurotoxic in neonatal rats. When administered in an acute, subconvulsive dose
      (500 mg/kg i.p.), MSG altered neurotransmitter content in discrete brain regions
      of adult (6 month old) and aged (24 month old) male Fischer-344 rats.
      Norepinephrine (NE) content was reduced in both the hypothalamus (16%) and
      cerebellum (11%) of adult rats, but was increased in both the hypothalamus (7%)
      and cerebellum (14%) of aged rats after MSG treatment. MSG also altered the
      dopamine content in adult rats in both the posterior cortex and the striatum,
      causing a reduction (23%) and an increase (12%), respectively. Glycine content in
      the midbrain of aged rats increased (21%) after MSG injection. Of particular
      interest is the widespread monoamine and amino acid deficits found in the aged
      rats in many of the brain regions examined. NE content was decreased (11%) in the
      cerebellum of aged rats. Dopamine content was reduced in both the posterior
      cortex (35%) and striatum (10%) of aged rats compared to adult animals. Cortical
      serotonergic deficits were present in aged rats with reductions in both the
      frontal (13%) and posterior cortex (21%). Aged rats also displayed deficits in
      amino acids, particularly the excitatory amino acids. There were glutamate
      deficits (9-18% reductions) in the cortical regions (posterior and frontal) as
      well as midbrain and brain stem. Aspartate, the other excitatory amino acid
      transmitter, was reduced 10% in the brainstem of aged rats. These data indicate
      that an acute, subconvulsive, dose of MSG may elicit neurochemical changes in
      both adult and aged male Fisher-344 rats, and that there are inherent age-related
      deficits in particular neurotransmitters in aged male Fisher-344 rats as
      indicated by the reductions in both monoamines and amino acids.

PMID- 1980347
TI  - A comparison of the psychopharmacological profiles of phencyclidine, ketamine and
      (+) SKF 10,047 in the trimethyltin rat model.
AB  - The potential neuroprotective effects of phencyclidine, ketamine and (+) SKF
      10,047 were investigated in the trimethyltin (TMT)-treated rat. Of the three
      drugs used in this study, only phencyclidine (5 mg/kg i.p.) reversed the
      behavioral hyperactivity and deficits in spatial localization of TMT-treated
      rats. Neurochemically, phencyclidine and (+) SKF 10,047 were without effect on
      the neurotransmitters (e.g. noradrenaline, dopamine, serotonin and 5-hydroxindole
      3-acetic acid), examined in the amygdaloid cortex and hippocampal regions, while
      ketamine increased the steady state concentrations of 5-HIAA in the amygdaloid
      cortex. These results suggest the involvement of the phencyclidine receptor in
      reversal of the behavioural impairments produced by TMT in rats. The significance
      of these results with respect to phencyclidine and sigma receptors is discussed.
      The lack of effect of (+) SKF 10,047 in this model may reflect behavioural
      differences between phencyclidine and sigma ligands. It may be concluded that the
      TMT model can be exploited for studying the mechanism of action of molecules
      liable to have an effect at the phencyclidine receptor site, as opposed to the
      sigma receptor.

PMID- 1980348
TI  - Electrophysiological effects of dermorphin on locus coeruleus neurons of rat.
AB  - Intracellular recording was used to study the effects of dermorphin on neurons of
      the locus coeruleus in the rat, in a totally submerged brain slice preparation.
      Dermorphin caused the inhibition of spontaneous firing of all neurons of the
      locus coeruleus tested, with an IC50 of 7 nM. Based on the inhibition of
      spontaneous firing rate, dermorphin was 16.5 times more potent than morphine.
      Larger concentrations of dermorphin (30-100 nM) further hyperpolarized the
      neurons of the locus coeruleus and simultaneously caused a reduction in input
      resistance. These effects were antagonized by naloxone, with a dissociation
      equilibrium constant of 0.8 nM. The hyperpolarization of neurons of the locus
      coeruleus, caused by dermorphin, was reversed at a membrane potential of -112 mV
      in this preparation. Furthermore, this hyperpolarization was blocked by cesium
      chloride and barium chloride. Thus, these data suggest that dermorphin binds to
      mu-opioid receptors on the cell membrane of neurons of the locus coeruleus. This
      leads to opening of the inward-going rectification potassium channels, resulting
      in the observed hyperpolarization of the membrane.

PMID- 1980349
TI  - Modulation of prodynorphin peptides release from the rat spinal cord in vitro.
AB  - The release of immunoreactive (ir-) dynorphin (DYN) and alpha-neoendorphin (alpha
      NEO) from spinal cord slices was investigated in rats. A stable, spontaneous, in
      vitro release of these peptides (6.7 +/- 0.3 of ir-DYN and 15.5 +/- 0.3
      fmol/min/g wet tissue of ir-alpha-NEO) was measured in superfusates using highly
      sensitive radioimmunoassays. The exposure of the slices to the superfusion medium
      containing 57 mM K+ or 50 microM veratridine increased circa three times the
      basal release of the peptides. The K(+)-evoked release of ir-alpha-NEO was Ca2(+)
      dependent, and the veratridine stimulation was abolished by 1 microM
      tetrodotoxin. Modulation of the alpha-neoendorphin release from the lumbar
      enlargement of the rat spinal cord by various neuroactive compounds was studied
      in vitro. Noradrenaline (1 microM) slightly enhanced the K(+)-induced release of
      ir-alpha-NEO, but was without effect on the basal release. On the other hand,
      GABA (10 microM) and muscimol (1 microM) inhibited the K(+)-stimulated release of
      the peptide. The effect of muscimol was attenuated by bicuculline (10 microM).
      Other compounds, such as serotonin (1 microM), naloxone (1 microM), U-50, 488H
      and bicuculline, altered neither the basal nor the K(+)-induced release. These
      data indicate that both ir-DYN and ir-alpha-NEO are stored in a releasable pool
      in the spinal cord, which supports the concept that prodynorphin peptides can
      serve as neurotransmitters in this structure. Furthermore, this study suggests
      that the spinal cord prodynorphin system may be under an inhibitory gabaergic and
      an excitatory catecholaminergic control.

PMID- 1980350
TI  - Cellular localization of somatostatin mRNA in rat retina.
AB  - In an attempt to determine the localization of the messenger RNA (mRNA) encoding
      somatostatin in the rat retina, we studied Sprague-Dawley rats by in situ
      hybridization histochemistry using radiolabelled oligodeoxyribonucleotides
      complementary for rat somatostatin mRNA. Among the layers of retina, we found
      specific labelling in the soma of some cells in the innermost and outermost
      laminae of the inner nuclear layer and in the ganglion cell layer; no specific
      labelling was observed in the inner and outer plexiform layers or in the outer
      nuclear layer. These data indicate the major site of somatostain synthesis within
      the rat retina.

PMID- 1980351
TI  - Effect of antiepileptic drugs on somatostatin release in vitro.
AB  - In the present study we investigated the effect of antiepileptic drugs on high
      potassium (50 mM) stimulated somatostatin release in rat cortical slices in a
      superfusion system. The somatostatin-like immunoreactivity (SLI) in superfusate
      was determined by radioimmunoassay. The antiepileptic drugs studied, vigabatrin,
      valproate, carbamazepine, phenobarbital, primidone, clonazepam and phenytoin were
      tested at a concentration range of 1-1000 microM). Of the drugs used vigabatrin
      had the most significant inhibitory effect on SLI release (IC50 = 240 microM).
      Vigabatrin also caused a concomitant, dose-dependent increase in superfusate
      gamma-amino butyric acid (GABA) level. A 30% decrease in the release of SLI
      followed incubation with valproate and carbamazepine, but only at high drug
      concentrations (1000 microM). Phenobarbital, primidone, clonazepam and phenytoin
      did not affect SLI release. Addition of GABA to superfusate caused a dose
      dependent decrease in the amount of SLI release (IC50 = 56 microM). In
      conclusion, at low concentrations the antiepileptic drugs had only minor effects
      on SLI release. At higher concentrations, however, vigabatrin and valproate
      decreased the release of SLI, which may relate to their ability to elevate tissue
      levels of GABA.

PMID- 1980352
TI  - [44th National Congress of the Italian Society of Anesthesia, Analgesia,
      Resuscitation and Intensive Therapy. Santa Margherita di Pulo, October 22-26,
      1990. Proceedings].

PMID- 1980353
TI  - [The use of muscle relaxants in continuous infusion in thoraco-abdomin al
      surgery].

PMID- 1980354
TI  - [Antagonism with flumazenil of sedation by benzodiazepine during loco-regional
      anesthesia].

PMID- 1980355
TI  - [Clinical evaluation of the effectiveness of flumazenil (RO 151788) after
      anesthesia with benzodiazepine only].

PMID- 1980357
TI  - Deliberations on nursing administration practice.
AB  - Blair and O'Brien orient us to the conference where this issue's articles on
      nursing administration education originated. The authors stress the critical need
      for development of nursing administration theory.

PMID- 1980356
TI  - [Our experience in the use of somatostatin in upper digestive hemorrhages].
AB  - The paper illustrates the Authors' personal experience of the use of somatostatin
      in high digestive hemorrhages. Endoscopy continues to be the principal method for
      hemorrhage diagnosis and therapy and the additional use of somatostatin
      undoubtedly accelerates recovery by blocking gastric and pancreatic secretions
      and blood flow at the splanchnic level.

PMID- 1980358
TI  - [New antiproliferative agents].

PMID- 1980359
TI  - [Upper respiratory tract infections: update and discussion. Meeting of the 29th
      Congress of French Pediatrics. Lyon, 4 July 1990. Proceedings].

PMID- 1980360
TI  - Guided mastery treatment of agoraphobia: beyond stimulus exposure.

PMID- 1980362
TI  - Dopamine receptor agonists and antagonists.

PMID- 1980361
TI  - Ipsapirone, a new anxiolytic drug, stimulates catecholamine turnover in various
      regions of the rat brain.
AB  - Ipsapirone, a new anxiolytic drug with a high affinity to 5-HT1A receptors, given
      in a dose of 10 mg/kg ip markedly accelerated noradrenaline disappearance after
      inhibition of tyrosine hydroxylase with alpha-methyl-p-tyrosine (250 mg/kg ip) in
      the cortex, hippocampus and hypothalamus of male Wistar rats. It also increased
      disappearance of dopamine and the level of 3,4-dihydroxyphenylacetic acid and
      homovanillic acid in the striatum. At the same time, the level of 5
      hydroxyindoleacetic acid was decreased in the cortex, striatum, hypothalamus, but
      not changed in the hippocampus. 8-OH-DPAT, a selective agonist of 5-HT1A
      receptors, used in a dose of 5 mg/kg sc was less effective, having accelerated
      noradrenaline disappearance in the cortex and hypothalamus, and having increased
      only the level of homovanillic acid in the striatum. The effect of ipsapirone on
      catecholamine turnover might be secondary in relation to inhibition of the
      serotonin neurons. A direct interaction between ipsapirone and its metabolite 1
      PP with alpha 1- and alpha 2-adrenoceptors is very likely, too.

PMID- 1980363
TI  - Clinical use of dopamine receptor agonists.
AB  - The development of novel DA receptor agonists, with various receptor
      selectivities, has confirmed the therapeutic utility of modulationing the
      peripheral dopaminergic system as Goldberg proposed 30 years ago. In addition to
      the acute therapy of heart failure, circulatory shock, and renal dysfunction, for
      which low dose DA has been standard therapy for many years, there is substantial
      evidence that DA receptor modulation will make a significant contribution to the
      chronic therapy of hypertension and congestive heart failure. However,
      development of drugs with adequate oral bioavailability remains a priority if we
      are to exploit fully these therapeutic possibilities.

PMID- 1980364
TI  - Pharmacological profile of the dopamine agonist, RS-45946.

PMID- 1980365
TI  - Eicosanoids, impotence and pharmacologically induced erection.

PMID- 1980366
TI  - Differential affinities of AF-DX 116, atropine and pirenzepine for muscarinic
      receptors of guinea pig gastric fundus, atria and urinary bladder: might atropine
      distinguish among muscarinic receptor subtypes?
AB  - The pA2 values and the Schild plots of the antimuscarinic drugs AF-DX 116,
      atropine and pirenzepine for muscarinic receptors of isolated guinea pig gastric
      fundus (acid secretion) and atrial and urinary bladder preparations (contractile
      force) obtained from the same animals were calculated against bethanechol as the
      agonist. The antimuscarinic drugs concentration-dependently shifted the
      concentration-response curves to bethanechol to the right without any change in
      the maximum response. The analysis of data based on Schild plots was consistent
      with a simple competitive antagonism, since regression slopes did not differ
      significantly from unity. The pA2 values indicated a significantly higher
      affinity of AF-DX 116 and atropine for atrial muscarinic receptors with respect
      to those of the gastric mucosa or urinary bladder. By contrast, in the case of
      pirenzepine the pA2 values for the three tissues did not differ significantly.
      These results suggest that each examined tissue apparently contains homogeneous
      population of acetylcholine muscarinic (M2) receptors. The pA2 values found for
      AF-DX 116 and atropine suggest, however, that the putative M2 subtype of atrial
      muscarinic receptor differs from both those of the gastric fundus and those of
      the urinary bladder.

PMID- 1980367
TI  - Effects of histamine on protein and glycoprotein production of isolated pig
      gastric mucosal cells.
AB  - The production of glycoprotein and protein by isolated pig gastric non-parietal
      cells was measured by incorporation of N-acetyl-[14C]-D-glucosamine [(
      14C]GlcNAc) and [3H]-L-leucine [( 3H]Leu), respectively, into acid insoluble
      material (AIM). Histamine enhanced incorporation of the tracers into cellular and
      released AIM in a concentration-dependent manner. The H2 receptor antagonist
      ranitidine completely blocked the effects of histamine (100 mumol/l) on [3H]Leu
      incorporation into cellular and released AIM (IC50 37 and 32 mumol/l,
      respectively) but had no inhibitory effect on the 16,16-dimethylprostaglandin-E2 
      and forskolin-stimulated tracer incorporation. The H1 receptor antagonist
      mepyramine did not inhibit the histamine effect. We conclude that histamine is a
      stimulant of protein, via H2 receptors, and glycoprotein production of isolated
      pig gastric non-parietal cells.

PMID- 1980368
TI  - Hemodynamic changes that accompany the pressor response to propranolol in
      urethane anesthetized rats subjected to alpha-blockade.
AB  - It has been shown that a paradoxical pressor response to a beta-blocker occurs in
      rats given an alpha-blocker. The dual-isotope microsphere technique was used to
      investigate the hemodynamic changes that accompany the pressor response to
      propranolol in phentolamine-treated, urethane-anesthetized rats. Rats were
      divided into four groups (n = 8 per group): group I received 10 min of saline
      infusion; group II received intravenous infusion of phentolamine (300
      micrograms/kg/min) for 10 min; group III received intravenous injection of
      propranolol (100 micrograms/kg) after 20 min of phentolamine infusion, and group
      IV received intravenous injection of saline after 20 min of phentolamine
      infusion. In groups I and IV, saline did not cause any significant hemodynamic
      changes. In group II, phentolamine decreased the mean arterial pressure (MAP) and
      total peripheral resistance (TPR) by 34 +/- 3 mm Hg and 0.28 +/- 0.07 mm
      Hg/min/ml, respectively. Arterial conductances in the skeletal muscle and skin
      were increased to 157 and 165% of control values, respectively. Cardiac output
      and conductances in other tissues and organs were not significantly affected. In
      rats given phentolamine (group III), propranolol raised MAP (+40 +/- 2 mm Hg) by
      increasing TPR (+0.41 +/- 0.03 mm Hg/min/ml). Vascular conductances in the
      skeletal muscle, skin and kidneys were decreased to 38, 57 and 69% of control
      values, respectively. Conductances in other tissues and organs were not
      significantly affected. Our results show that propranolol raised MAP by
      increasing flow resistance, primarily via the reversal of the vasodilator effects
      of phentolamine in the muscle and skin.

PMID- 1980369
TI  - [FDA phase II and phase III drug evaluation of antipsychotic agents].

PMID- 1980370
TI  - [Problems on FDA phase IV drug evaluation of antipsychotic agents].

PMID- 1980371
TI  - Phencyclidine-induced disruption of an aversely motivated two-choice successive
      discrimination in the rat.
AB  - Rats were trained to performed an aversely motivated discriminative task in a
      shuttle-box. The administration of phencyclidine (PCP), 2 mg kg-1 SC at -20 min,
      produced disruption of discriminative performance and an increase in intertrial
      crosses. There were no changes in avoidance performance or in avoidance latency.
      Pretreatment with haloperidol, 0.1 or 0.2 mg kg-1 SC at -40 min, or remoxipride 8
      mg kg-1 IP at -30 min, did not antagonize the PCP-induced disruption of
      discriminative performance, nor was the PCP-induced increase in number of
      intertrial crosses antagonized. In fact, there appeared to be a further increase
      in intertrial crosses, above PCP levels, by haloperidol treatment and this effect
      was statistically significant after remoxipride treatment. The present results,
      together with previous observations that also d-amphetamine disrupts
      discriminative conditioned avoidance behavior, suggest the possibility that this
      model could be used in the search for new, non-dopaminergic, antipsychotic drugs.

PMID- 1980372
TI  - Metabolic mapping of the effects of intravenous methamphetamine administration in
      freely moving rats.
AB  - The 2-[14C]deoxyglucose method was used to examine the effects of acute
      intravenous administration of methamphetamine (0.5-2.5 mg/kg) on rates of local
      cerebral glucose utilization in freely-moving rats. These effects were correlated
      with the effects of methamphetamine on locomotor activity assessed simultaneously
      in the same animals. Methamphetamine administration resulted in widespread dose
      dependent increases in glucose utilization within structures of the
      extrapyramidal motor system. Rates of glucose utilization were positively
      correlated with locomotor activity in the globus pallidus, substantia nigra
      reticulata, entopeduncular nucleus, subthalamic nucleus, and the lateral
      cerebellar cortex. In contrast, within the limbic system alterations in metabolic
      activity were smaller and more selective. Glucose utilization was increased in
      the nucleus accumbens at all doses tested, but alterations in glucose utilization
      in the ventral tegmental area, amygdala, and anterior cingulate were observed
      only at the highest doses of methamphetamine tested. Significant increases in
      rates of glucose metabolism were also found in the substantia nigra compacta and
      in the median and dorsal raphe nuclei. Dopamine and serotonin are depleted in
      these regions, as well as in the ventral tegmental area where glucose utilization
      was also increased, following chronic treatment with high doses of
      methamphetamine. These changes in glucose utilization may be indicative of
      disturbances in the biochemical processes involved in the neurotoxic effects of
      methamphetamine.

PMID- 1980373
TI  - Effects of chronic treatments with amineptine and desipramine on motor responses
      involving dopaminergic systems.
AB  - The acute effects of increasing doses of the antidepressant drugs amineptine (5
      40 mg/kg, IP) and desipramine (5-20 mg/kg IP) were studied in mice on three
      parameters of the activity (the horizontal activity, the vertical activity and
      the number of small movements without displacement) measured in a computerized
      Digiscan actimeter. The horizontal and vertical activities were dose dependently
      and similarly increased by acute amineptine, whereas the number of movements
      without displacement was increased up to 10 mg/kg with no further significant
      modification up to 40 mg/kg; in contrast, all three parameters were reduced in an
      identical manner by desipramine. The changes in the responses to the selective D
      1 dopamine (DA) receptor agonist SK&F 38393 (1.87-30 mg/kg, SC), to the selective
      D-2 DA receptor agonist LY 171555 (0.1-1.6 mg/kg, SC) and to the selective DA
      uptake inhibitor GBR 12783 (1.25-20 mg/kg, IP) were measured on the three
      parameters of activity in mice chronically treated with amineptine (20 mg/kg, IP
      twice daily during 15 days) or by desipramine (10 mg/kg, IP, twice daily during
      15 days). The chronic treatments with amineptine or desipramine did not modify
      the motor stimulant effects GBR 12783 and of SK&F 38393 on the three parameters
      (excepted for a slight modification of the horizontal activity for 7.5 mg/kg SK&F
      38393 in mice chronically treated with amineptine). In contrast, the motor
      inhibitory effects of the lowest doses of LY 171555 (0.1-0.4 mg/kg) were strongly
      reduced in mice chronically treated with amineptine or desipramine but only on
      the horizontal activity with no change on the vertical activity and on the number
      of small movements without displacement.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1980375
TI  - Treatment of neuroleptic induced akathisia with the 5-HT2 antagonist ritanserin.
AB  - Akathisia is a frequent and distressing side effect of antipsychotic medication.
      Little is known about its pathophysiology. Treatment trials of serotonin
      antagonists in Parkinson's disease and neuroleptic-induced Parkinsonism have been
      disappointing, with the possible exception of akathisia which has been reported
      to respond favorably to ritanserin. We report first results of a single-blind
      trial of ritanserin in the treatment of neuroleptic-induced akathisia. Ten
      patients received a mean dose of 13.5 mg/day (SD +/- 5.8) ritanserin for 2 to 4
      days. Treatment response was assessed by the Hillside Akathisia Scale (HAS). HAS
      baseline ratings were 16.4 (+/- 6). After 3 days of treatment, these values
      dropped to 7.4 (+/- 5.2). This amelioration was statistically significant (p =
      .0069 matched-pairs signed rank test). Two patients did not respond. These
      results, although preliminary in nature, are encouraging and warrant further
      studies.

PMID- 1980374
TI  - Cocaine and local anesthetics: stimulant activity in rats with nigral lesions.
AB  - Cocaine and several other local anesthetics were tested for their ability to
      induce rotational behavior in rats with unilateral 6-hydroxydopamine lesions of
      substantia nigra. Acute administration of bupivacaine, chloroprocaine,
      etidocaine, lidocaine, mepivacaine, procaine or tetracaine failed to induce
      active rotation in this sensitive assay of dopamine agonist activity. On the
      other hand, cocaine or dimethocaine treatment induced active rotation directed
      ipsilaterally to the lesioned side, indicating indirect dopamine agonist
      activity. Repeated administration of cocaine or dimethocaine at 1-week intervals
      resulted in increased rotational response (i.e., sensitization) while there was
      no suggestion of sensitization or induction of rotational behavior after weekly
      repeated administration of procaine or tetracaine. Daily administration of
      mepivacaine, procaine or tetracaine for 5 days also failed to induce rotation.
      Dimethocaine thus was found similar to cocaine and different from the other local
      anesthetics tested both in terms of frank stimulant activity and development of
      sensitization upon repeated administration.

PMID- 1980376
TI  - Repartitioning effect of a mixed beta-agonist on body composition.
AB  - Subcutaneous administration of a mixed beta-agonist to young rats induced no
      changes in animal growth and food conversion efficiency. However, a
      repartitioning effect was found with increases in lean tissue and decreases in
      body fat. The enhancement of muscle protein deposition was attributed to a fall
      in protein breakdown as muscular cathepsin A activity was lower in treated rats.
      A reduction of muscle reduction-oxidation state is associated to those changes in
      protein metabolism.

PMID- 1980377
TI  - Temporary cessation of long-term maintenance treatment with omeprazole in
      patients with H2-receptor-antagonist-resistant reflux oesophagitis. Effects on
      symptoms, endoscopy, serum gastrin, and gastric acid output.
AB  - To study the effects of sudden withdrawal of long-term maintenance therapy with
      omeprazole for up to 4 years, 14 patients with resistant reflux oesophagitis were
      asked to stop their treatment temporarily. Ten days after withdrawal median basal
      acid output had increased significantly (p = 0.01) from 0 (range, 0-1.18) on day
      1 to 1.95 (range, 0-8.45) mmol/h on day 10. Median serum gastrin levels were
      raised during treatment with omeprazole but decreased significantly from 166 to
      42 ng/l within the 10 days of the study (p = 0.01). The median integrated gastrin
      response after meal stimulation decreased significantly (p less than 0.001) from
      758.6 ng/l on day 1 to 267.9 ng/l on day 10. On day 10 after withdrawal of
      omeprazole all patients had endoscopic and symptomatic evidence of recurrent
      oesophagitis. Reflux patients receiving maintenance treatment with omeprazole for
      up to 4 years showed prompt normalization of serum gastrin levels and return of
      gastric acid production within 10 days after stopping the treatment.
      Consequently, there was a fast recurrence of aggravation of reflux symptoms and
      oesophagitis.

PMID- 1980378
TI  - Spontaneous bilateral rupture of kidneys in a patient with polyarteritis nodosa.
      A case report.
AB  - A previously well 42-year-old man presented with a three-hour history of pain in
      the right flank of acute onset. At laparotomy he was found to have a ruptured
      right kidney which was treated by nephrectomy. Eight days later he developed
      similar symptoms on the left: at operation 21 of blood were drained and
      nephrostomy and catheterisation carried out. He recovered after a complicated
      postoperative course, and histological examination of the removed kidney, and
      biopsy specimens, showed classic polyarteritis nodosa. This is a rare cause of
      spontaneous rupture of the kidney but must be considered whenever a patient
      presents with renal haemorrhage of unknown cause.

PMID- 1980379
TI  - Spontaneous neurodegeneration in transgenic mice with mutant prion protein.
AB  - Transgenic mice were created to assess genetic linkage between Gerstmann
      Straussler-Scheinker syndrome and a leucine substitution at codon 102 of the
      human prion protein gene. Spontaneous neurologic disease with spongiform
      degeneration and gliosis similar to that in mouse scrapie developed at a mean age
      of 166 days in 35 mice expressing mouse prion protein with the leucine
      substitution. Thus, many of the clinical and pathological features of Gerstmann
      Straussler-Scheinker syndrome are reproduced in transgenic mice containing a
      prion protein with a single amino acid substitution, illustrating that a
      neurodegenerative process similar to a human disease can be genetically modeled
      in animals.

PMID- 1980380
TI  - Systemic drug interactions with topical glaucoma medications.
AB  - Topically administered ophthalmic medications are capable of attaining clinically
      important serum concentrations, as evidenced by the variety of systemic side
      effects they can produce. These drugs are therefore also capable of interacting
      with other drugs administered orally and intravenously. This is especially
      important when medications are administered to an elderly population, who are
      often receiving multiple medications. The Physician's Desk Reference and the
      United States Pharmacopeia Drug Information directory contain numerous warnings
      of potential interactions between topical glaucoma medications and systemically
      administered drugs. Unfortunately, literature supporting such interactions is
      limited, both in quantity and quality, being anecdotal in many cases. This report
      summarizes available information regarding the nonocular interactions between
      topical ophthalmic glaucoma medications and other systemically administered
      medications. Clinical evidence of these interactions is lacking in many cases.

PMID- 1980381
TI  - Azidothymidine (AZT) in the treatment of symptomatic HIV-1-infected hemophiliacs.
AB  - Twenty-one immunodeficiency virus 1 (HIV 1)-positive hemophilic patients were
      treated with Azidothymidine (AZT) for symptomatic HIV infection. The median
      observation period was 20.5 months. At 25 months the probability of survival was
      82%, the probability of progression of disease from CDC III or IV C2 to IV C1
      (AIDS) was 20% in patients on continuous AZT treatment and 50% in patients with
      interruption of treatment. Three patients developed severe leukopenia and 3
      patients severe anemia during AZT treatment. In 1 patient a dose-dependent
      striking increase of transaminases during AZT treatment was observed. In 7
      patients treatment was interrupted, in 1 patient because of anemia, in 1 because
      of pruritus and in 5 patients because of non-compliance. No significant changes
      in the consumption of clotting factor concentrates and number of bleeding
      episodes before and during AZT treatment were noted. We conclude, that both
      hematological and non-hematological side effects of AZT in HIV 1-infected
      hemophilic patients are comparable to those seen in other risk groups. AZT does
      not increase the bleeding tendency in this patient group.

PMID- 1980382
TI  - [Sotalol. Beta-blockade and class III antiarrhythmic effect].

PMID- 1980383
TI  - Disposition and nephrotoxicity of 3-amino-1-hydroxypropylidene-1,1-bisphosphonate
      (APD), in rats and mice.
AB  - The purpose of this study was to investigate the disposition and the
      nephrotoxicity of 3-amino-1-hydroxypropylidene-1, 1-bisphosphonate (APD
      pamidronate) in order to elucidate the mechanism of the non-linearity of the
      renal elimination of this drug. The fate of APD labelled with [14C]APD was
      studied in mice and rats for a range of doses (0.5-40 mg/kg) and indicators of
      renal function were monitored. In both species, the percentage of dose excreted
      during the first 24-h after treatment fell dramatically as a function of the
      dose. However, the renal burden of APD rose linearly for doses of APD below 10
      mg/kg and increased non-linearly over this threshold. In contrast the
      concentration of APD in both bone and liver, which together account for a large
      proportion of the dose, appeared to increase proportionally with dose. There was
      no evidence, therefore, that the non-linear renal elimination of APD was due to
      an increased uptake of APD by tissues. Conversely, the significant fall in the
      renal excretion of APD was paralleled by a striking loss in body weight, and for
      high doses, by a fall in the creatinine clearance. An increased enzymuria
      suggested the loss of brush border membranes and the release of lysosomal
      contents by proximal tubular cells. Morphological studies confirmed this and
      revealed a focal proximal tubular necrosis 6 days post dosing. We conclude that
      the nephrotoxicity of APD accounts for the non-linear renal elimination of this
      drug.

PMID- 1980384
TI  - Racial differences in baseline cyclic adenosine monophosphate concentrations per
      million T-lymphocytes and protein concentrations.
AB  - beta-Adrenergic blockers are less efficacious as monotherapy for the treatment of
      hypertension in blacks as compared with whites. Because beta-adrenergic
      stimulation and blockade differ between racial groups, biochemical differences in
      the beta-adrenergic pathway may exist. It is the intent of this report to show
      underlying similarities and differences, at least in part, in the beta-adrenergic
      pathway (e.g., baseline cAMP and protein concentrations) using the T-lymphocyte
      as the model system. A total of 20 (n = 10 black, n = 10 white) normotensive male
      volunteers were recruited, begun on a low-sodium diet to normalize serum
      catecholamines, and blood was collected for lymphocyte beta-receptor isotherm
      binding experiments and cAMP determination. There were no differences in Bmax,
      sites per cell, or kd. Basal cAMP concentrations were significantly higher in the
      black group (16.0 +/- 9.8 pmol/10(6) cells) compared with the white group (7.0 +/
      1.8 pmol/10(6) cells) (p less than 0.05). Protein levels from the lymphocyte
      suspension were also higher in the black group (1,081.0 +/- 367.7 micrograms/ml)
      compared with the white group (766.8 +/- 220.4 micrograms/ml) (p less than 0.05).
      Normalization of cAMP for protein yielded 83.2 +/- 55.4 fmol/micrograms protein
      in the black group and 56.6 +/- 29.8 fmol/micrograms protein in the white group
      (p = 0.11). Altered protein levels may be a confounding variable in studies of
      this type. Further work is necessary to identify the nature and significance of
      this protein elevation, its relationship to the adenylate cyclase system in
      lymphocytes, and the source of the cAMP elevation noted herein.

PMID- 1980385
TI  - [Antidepressive agents in the elderly].
AB  - Depressive disorders are the most common psychiatric illness in the elderly. All
      tricyclic antidepressants show comparable therapeutic efficacy, thus the choice
      of drug is based on their side effects profiles rather than on degree of
      therapeutic efficacy. The secondary amines nortriptyline and desipramine are
      drugs of choice for the elderly depressive patient because of their relatively
      mild side effects profile. New-generation antidepressants remain second choice.
      Patients suffering from a psychotic depression often require a combination of an
      antidepressant drug with an antipsychotic drug. Addition of lithium to a cyclic
      antidepressant can produce a rapid and lasting remission in patients with a major
      depressive disorder who do not respond to a cyclic antidepressant alone.
      Treatment with MAO-inhibitors or electroconvulsive therapy can also be considered
      in refractory cases.

PMID- 1980386
TI  - [Multiple endocrine neoplasms type I].
AB  - The patient had been treated ten years previously for acromegaly. At present he
      was in hypercalcaemic crisis owing to multiple hyperparathyroid adenomas. He had
      multiple small pancreatic glucagonomas and a malignant duodenal gastrinoma which
      led to recurrent episodes of duodenal and gastric ulcers with perforations and
      hemorrhages. The hypercalcaemia increased the hypergastrinaemia significantly and
      probably accelerated the ulcer diathesis. This patient illustrates well how
      severe and complicated the clinical situation can be in patients with MEN-1 and
      emphasizes the importance of being aware of the syndrome.

PMID- 1980387
TI  - [The participation of histamine and serotonin in the genesis of acute kidney
      failure in patients with hemorrhagic fever with renal syndrome].
AB  - In order to explore possible involvement of histamine and serotonin in acute
      renal failure related to hemorrhagic fever with renal syndrome (HFRS), selected
      markers or renal lesions have been compared with biochemical findings in highly
      severe cases. Literature reports and the study results lead the authors to
      conclude that histamine and serotonin are obviously pathogenetic determinants of
      HFRS since their concentrations in plasma of these patients are increased 3-fold.
      It is suggested that the biologically active substances may be a link between
      renal disease and hyperergy in severe and critical disease forms.

PMID- 1980388
TI  - [Immunological research in cryptorchism accompanied by infertility].
AB  - An overview of the recent literature shows that immune processes, primarily
      autoimmune events, occur in cryptorchid patients with infertility. The aim of
      this study was to examine cellular and systemic immune responses in these
      patients. Fifteen infertile cryptorchid patients have been investigated for the
      presence of circulating autoantibodies using immunofluorescence and
      immunoperoxidase techniques. The study evaluated selected testicular structures
      and levels of immune products (IgA, IgG, IgM or immune complexes) in testicular
      biopsy samples. The results of the study showed no relation of infertility to
      systemic immune disturbance in most cryptorchid patients.

PMID- 1980389
TI  - [Effect of ketamine anesthesia on patients with severe trauma at the pre-hospital
      stage on the course and outcome of shock].
AB  - Under study were remote results of treatment of patients with critical traumas
      followed by shock who were given prehospital Ketamine anesthesia. The data
      obtained were compared with remote results of treatment of patients who did not
      receive anesthesia at the prehospital stage or who were given narcotic analgetic
      drugs for anesthesia. Reliable data were obtained showing the course of trauma
      disease to be more favourable in a group of patients who were given Ketamine
      anesthesia at the prehospital stage.

PMID- 1980390
TI  - [Prevention of the first gastroesophageal hemorrhage in patients with portal
      hypertension].

PMID- 1980391
TI  - Drugs recently released in Belgium. Fluconazole--xamoterol fumarate.

PMID- 1980392
TI  - Pharmacological and clinical aspects of glaucoma therapy.

PMID- 1980393
TI  - [Effects of disodium cromproxate on spontaneous beating and action potentials of
      cultured myocardial cells of neonatal rats].
AB  - Disodium cromproxate (SCP) is an anti-allergic drug. SCP 80, 160, 320 mumol/L
      markedly increased spontaneous beating rate of cultured myocardial cells,
      especially SCP 160 mumol/L. SCP 320, 640 mumol/L increased the amplitude, maximal
      rate of rise and prolonged the duration of the action potentials of the cultured
      myocardial cells of neonatal rats. The maximal diastolic potential was not
      affected by SCP.

PMID- 1980394
TI  - Primary structure of the gene coding for the haemagglutinin of influenza virus
      A/Leningrad/385/80(H3N2): detection of a point mutation responsible for the
      antigenic drift.
AB  - Primary structure of the gene coding for haemagglutinin (HA-gene) of influenza
      virus A/Leningrad/385/80(H2N2) isolated during the epidemics of influenza in
      Leningrad in 1980 was determined. The close relationship of HA gene of this virus
      to the corresponding gene of the virus A/Bangkok/1/79(H3N2) was confirmed. It was
      shown that a single mutation in an antigenic site (the change from isoleucine to
      leucine at position 51 of HA1 gene) caused an antigenic drift. One silent
      mutation was detected (nucleotide 428 of HA1 gene) which points at the
      relatedness of strains A/Leningrad/385/80 with A/Bangkok/2/79 and with other more
      recent strains. These data allowed to determine the position of the strain
      A/Leningrad/385/80 HA gene regarding to the evolutionary relationships of HA
      genes of influenza A (H3N2 subtype) viruses. The branch leading to the above
      mentioned strain is supposed to start from a point common for strains isolated
      following A/Bangkok/1/79. The mutations of HA genes presented in this subgroup
      were analysed supporting the notion on limited evolutionary potential of the
      subtype H3N2 influenza viruses.

PMID- 1980395
TI  - Monoclonal antibodies against the nucleoprotein of mumps virus: their binding
      characteristics and cross-reactivity with other paramyxoviruses.
AB  - Twelve monoclonal antibodies (MoAbs) directed against the nucleoprotein (NP) of
      mumps virus were analysed for their binding characteristics. Competitive binding
      in enzyme-linked immunosorbent assay divided them into eight groups. Two of the
      MoAbs recognized exclusively 66 kD polypeptide of NP, two recognized 66 kD and 60
      kD, and one recognized 66 kD (and 60 kD to a lesser extent) in Western blot
      assays under either denaturing or partially denaturing conditions. Under
      partially denaturing condition, another five MoAbs reacted faintly but the
      remaining two did not react at all. Under denaturing condition, on the other
      hand, these seven MoAbs showed little reactivity with any polypeptide.
      Furthermore, denaturation resulted in formation of other polypeptides 55 kD, 50
      kD, and 43 kD which all were detected by MoAbs reacting with 66 kD and/or 60 kD.
      Previously demonstrated antigenic cross-reactivity among the NPs of mumps virus
      and those of human parainfluenza viruses type 2 and type 4 in
      radioimmunoprecipitation assay using polyclonal antisera was confirmed by an anti
      NP MoAb which showed little reactivity in denaturing Western blot assay.

PMID- 1980396
TI  - Immunogenicity of peptides cleaved by cyanogen bromide from Japanese encephalitis
      virus envelope glycoprotein E.
AB  - Envelope glycoprotein (E) prepared from purified Japanese encephalitis (JE) virus
      was cleaved with cyanogen bromide (CNBr) followed by sodium dodecyl sulphate
      polyacrylamide gel electrophoresis (SDS-PAGE). Mice were immunized with 36 kD, 27
      kD, and 8 kD bands from CNBr-cleaved and 54 kD band from control specimens.
      Neutralization test was positive in one out of two anti-54 kD, in none of the
      anti-36 kD, and all of anti-27 kD and anti-8 kD sera at 1:10 dilution.
      Geometrical mean ELISA titre was the highest for anti-54 kD followed by anti-36
      kD, anti-27 kD, and anti-8 kD sera. Reactivity of these sera to CNBr-cleaved
      fragments in Western blotting indicated that the 8 kD fragment was a part of the
      27 kD but was not included in the 36 kD fragment, while the 27 kD and 36 kD
      fragments shared an overlapping part. These fragments were located on the E
      protein by N-terminal amino acid sequencing of each fragment purified by reversed
      phase high-performance liquid chromatography and by comparison with the
      nucleotide sequence of the E protein gene. The 36 kD fragment was located between
      the third and the ninth methionine and covered most of the N-terminal side of the
      E protein. In contrast, the 27 kD fragment was located between the fourth and the
      tenth methionine and included the 8 kD fragment which was situated between the
      ninth and the tenth methionine near to the C-terminus of the E protein.
      Denaturation-resistant neutralizing epitope(s) appeared to be present on the 8 kD
      fragment, but not on the 36 kD fragment.

PMID- 1980397
TI  - Serum antibodies to human enteric coronavirus-like particles in Australia, South
      Africa, Indonesia, Niue, and Papua New Guinea.
AB  - Relatively high levels of antibody to human enteric coronavirus-like particles
      were detected in the sera from rural Aborigines in Australia. Levels were
      generally much lower in the sera from urban Aborigines, and extremely low to not
      detectable in the sera from Europeans. Antibody to coronavirus-like particles was
      also detected in the sera from rural blacks from South Africa, in the sera from
      Indonesia and Niue, and also possibly in the sera from rural villagers from Papua
      New Guinea, but in the latter case at only very low level.

PMID- 1980398
TI  - Identification of an immunodominant region on the isolated bovine leukaemia virus
      (BLV) major envelope protein gp51 by monoclonal antibodies presumably not exposed
      during natural BLV infection.
AB  - A panel of newly isolated monoclonal antibodies (MoAbs) is described which are
      specific for bovine leukaemia virus (BLV) envelope protein gp51. Epitope mapping
      using competition antibody binding assays and binding studies with gp51-related
      fusion proteins and synthetic peptides show that they are directed against seven
      independent antigenic determinants. Four of them are unrelated to the epitopes
      described earlier (Bruck et al., 1982a). We define three binding regions for the
      MoAbs on the gp51 molecule. The region between amino acids 170 and 217 is highly
      immunogenic when the isolated protein is used for immunization, and seems to be
      inaccessible for immune recognition when gp51 is associated with the virus
      envelope as it occurs during natural BLV infection.

PMID- 1980399
TI  - Inactivating and mutagenic effects of nitrosoguanide on human cytomegalovirus.
AB  - Human cytomegalovirus (HCMV) was exposed for 24 hr to 10-30 micrograms/ml
      nitrosoguanidine (NG) at different times postinfection. NG treatments performed
      24 to 48 hr after infection of human IAFP-1 fibroblasts with HCMV interfered most
      significantly with the replication of the virus. No correlation was found,
      however, between the inactivating effect of NG at this particular stage of the
      replication cycle and the induction of HCMV temperature-sensitive mutants. All
      the 17 HCMV mutant strains isolated on this occasion showed the same BamHI, Cfo
      I, Hpa II and Sph I restriction profiles which is indicative of mutations caused
      by single base changes.

PMID- 1980400
TI  - Replication of Langat virus in immunocompetent cells of mice subjected to
      immobilization stress.
AB  - Immobilization stress (hypokinesis) in Balb/c mice may aggravate asymptomatic
      infection with Langat virus (strain TP-21) as evidenced by 4-fold increased
      lethality in comparison with control animals. The virus levels in the spleen and
      brain of stressed and infected mice and the in vitro yield of the virus in
      immunocompetent cells derived from stressed mice were significantly higher than
      in controls. Enhanced virus replication in latter cells may contribute to
      increased accumulation of the infectious agent in lymphatic tissues, which would
      facilitate virus invasion into CNS followed with acute disease and death of
      animals.

PMID- 1980401
TI  - The immune response to influenza vaccines.
AB  - Specific immunity to influenza is associated with a systemic immune response
      (serum haemagglutination inhibition antibody), local respiratory immune response
      (virus-specific local IgA and IgG antibodies in nasal wash), and with the cell
      mediated immune response. Both inactivated and live influenza vaccines induce
      virus-specific serum antibody which can protect against infection with influenza
      virus possessing the same antigenic specificity. In the absence of serum
      antibodies, local antibodies in nasal wash are a major determinant of resistance
      to infection with influenza virus. In comparative studies in humans it was shown
      that nasal secretory IgA develops chiefly after immunization with live cold
      adapted (CA) vaccine, but persistent nasal secretory IgG was detected in both CA
      live and inactivated vaccines. The origin of nasal wash haemagglutination
      inhibition (HI) antibodies is not completely known. Recently it was found that
      cytotoxic T-cells (CTL) play an important role in immunity against influenza and
      in clearance of influenza virus from the body. In primed humans, inactivated
      influenza vaccine stimulates a cross-reactive T-cell response, whereas the
      ability of inactivated vaccine to stimulate such immunity in unprimed humans has
      not been determined. Data on the T-cell response to live vaccine in humans are
      limited to the development of secondary T-cell responses in primed individuals
      vaccinated with a host-range (HR) attenuated vaccine. The data obtained have
      shown that immunity induced by inactivated influenza vaccines is presumably
      dependent on the stimulation of serum antibody. Live CA vaccines not only
      stimulate a durable serum antibody response, but also induce long-lasting local
      respiratory tract IgA antibody that plays an important role in host protection.

PMID- 1980402
TI  - Monoclonal antibodies in the treatment of infectious disease. Proceedings of a
      symposium. December 4, 1989, Atlanta, Georgia.

PMID- 1980403
TI  - Genetic relatedness of Legionella longbeachae isolates from human and
      environmental sources in Australia.
AB  - The genetic relatedness of Legionella longbeachae isolated in Australia since
      1987 was investigated by restriction fragment length polymorphism (RFLP) analysis
      and allozyme electrophoresis. Three radiolabeled probes were used in Southern
      hybridizations for the RFLP studies. They were Escherichia coli 16S and 23S rRNA
      and cloned fragments of L. longbeachae selected empirically from genomal banks in
      lambda and a cosmid. The legionellae included in the study comprised 11
      Legionella longbeachae serogroup 1 organisms isolated from humans, 28 L.
      longbeachae serogroup 1 isolates from environmental sources, and 3 L. longbeachae
      serogroup 2 environmental isolates. These were compared with the American Type
      Culture Collection reference strains of both serogroups and some other related
      Legionella species. Results of allozyme and RFLP analysis showed that all the
      isolates from humans and all but three of the environmental L. longbeachae
      serogroup 1 isolates were closely related. They were also closely related to L.
      longbeachae serogroup 1 ATCC 33462. There was wider variation among the three L.
      longbeachae serogroup 2 environmental isolates. One of these was closely related
      to L. longbeachae serogroup 2 ATCC 33484. RFLP studies with the rRNA probe
      provided the most discrimination among isolates but did not distinguish between
      the two serogroups.

PMID- 1980404
TI  - Dehydroepiandrosterone and a beta-agonist, energy transducers, alter antioxidant
      enzyme systems: influence of chronic training and acute exercise in rats.
AB  - We examined the influence of dehydroepiandrosterone (DHEA), a beta-agonist, and
      exercise training on enzymes that detoxify toxic oxygen species. Feeding 0.4%
      DHEA decreased hepatic cytosolic (c) selenium-dependent glutathione peroxidase
      (GPX), (-26%, P less than 0.0001) and increased hepatic mitochondrial (m) Mn
      superoxide dismutase (SOD), (+38%, P less than 0.001). DHEA decreased myocardial
      c-GPX (-21%, P less than 0.05) when compared to a beta-agonist (beta A; L644969
      Merck and Co.) fed at 5 ppm but neither differed from the Control (C). In
      contrast, the beta A increased hepatic m-GPX (+25%, P less than 0.05). In
      skeletal muscle, DHEA and beta A decreased muscle c-GPX by 20 and 12%,
      respectively (P less than 0.0009). DHEA increased both muscle (+20%, P less than
      0.01) and myocardial (+20%, P less than 0.05) c-glutathione S-transferase (GST)
      over beta A (+20%, P less than 0.01) but neither was significantly different from
      C. Similar to DHEA, chronic training (Tr) (1 h/day, 5 days/week at 27 m/min, 15%
      grade on treadmill) decreased hepatic c-GPX (-16%, P less than 0.003). Tr
      elevates muscle c-GPX (+36%, P less than 0.05) in C. Tr increased myocardial c
      GPX by 28% in the beta A-treated rats, whereas Tr decreased myocardial c-GPX by
      22% in the C (P less than 0.05, interaction). One hour of acute exercise (Ex)
      (70% VO2 max relative work load) decreased hepatic homogenate catalase (-12%, P
      less than 0.02) and increased hepatic m-Mn SOD (+28%, P less than 0.03). Ex
      decreased myocardial c-GST (P less than 0.05) only in the DHEA-treated rats. DHEA
      and Tr may improve efficiency of oxygen utilization at the tissue level with
      lower antioxidant enzyme activity in liver and locally protective up-regulation
      in muscle. beta A stresses oxygen utilization systems and liver responds by up
      regulation of antioxidant enzymes. The increase in myocardial c-GPX activity in
      the beta A-treated group may be a protective effect against indirect
      catecholamine-induced myocardial necrosis which results from free radical
      generation.

PMID- 1980405
TI  - Avian liver 3-hydroxy-3-methylglutaryl-CoA synthase: distinct genes encode the
      cholesterogenic and ketogenic isozymes.
AB  - Full length cDNA (1.85 kb) coding for an avian liver 3-hydroxy-3-methylglutaryl
      CoA (HMG-CoA) synthase has been isolated and sequenced. The cDNA isolation relied
      on hybridization to a 32P-labeled oligonucleotide coding for a portion of the
      active site of HMG-CoA synthase. The identity of the avian liver cDNA was
      confirmed by comparison of the deduced amino acid sequence with experimentally
      determined protein sequence data generated upon isolation and analysis of several
      cysteine-containing tryptic peptides prepared from the purified ketogenic avian
      liver enzyme. Structural comparisons with the hamster enzyme also support this
      assignment. In liver, two distinct forms of HMG-CoA synthase exist to support
      cholesterogenic and ketogenic pathways, although this latter pathway accounts for
      most of the enzyme activity. In order to determine which isozyme is encoded by
      the isolated avian liver cDNA, the deduced amino acid composition, protein
      sequence, and pI have been compared with the corresponding protein chemistry data
      that were experimentally determined using the ketogenic enzyme. Results of these
      comparisons unambiguously indicate that the cDNA encodes the avian liver
      cholesterogenic enzyme. Observed differences between deduced and empirically
      determined sequence data rule out the possibility that differential splicing of a
      primary transcript derived from one gene can account for both isozymes.

PMID- 1980406
TI  - [Clinical and laboratory problems of modern chemotherapy and chemoprophylaxis of
      infections].

PMID- 1980407
TI  - 1,2-Dichloropropane (DCP) toxicity is correlated with DCP-induced glutathione
      (GSH) depletion and is modulated by factors affecting intracellular GSH.
AB  - Acute 1,2-dichloropropane (DCP) poisoning in humans is relatively frequent in
      Italy, where DCP is widely diffused as a constituent of commercial solvents and
      dry cleaners. In this study we have investigated the effects of DCP on
      intracellular glutathione (GSH) content in main target tissues of male Wistar
      rats, i.e. liver, kidney and blood, in order to establish if a correlation
      between DCP-induced GSH depletion and tissue damage exists. Administration of DCP
      (2 ml/kg body weight orally) caused a dramatic loss of tissue GSH occurring 24 h
      after DCP intoxication, followed by a slow restoration approaching physiological
      levels after 96 h. GSH depletion was associated with a marked increase in serum
      GOT, GPT, 5'-nucleotidase, gamma-glutamyl transpeptidase, alkaline phosphatase,
      urea and creatinine, and a significant degree of hemolysis. When animals were
      pretreated with a GSH depleting agent, buthionine-sulfoximine (BSO) (0.5 g/kg
      body weight) i.p. 4 h before DCP intoxication, an increase of overall mortality
      was found, significantly different from the group of animals treated with DCP
      alone. On the contrary, the administration of a GSH precursor, N-acetylcysteine
      (NAC) i.p. (250 mg/kg body weight) 2 and 16 h after DCCP intoxication prevented
      the dramatic loss of cellular GSH and reduced the extent of injury in target
      tissues, as demonstrated by laboratory indices. Furthermore, statistical analysis
      of the data revealed a correlation between: (1) depletion of liver GSH and
      increase in serum GOT, GPT, 5'-nucleotidase, (2) depletion of kidney GSH and
      increase in serum urea and creatinine and (3) depletion of blood GSH and the
      occurrence of hemolysis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1980408
TI  - In vivo biliary excretion and in vitro cellular accumulation of thyroxine by rats
      or cultured rat hepatocytes treated with a novel histamine H1-receptor
      antagonist.
AB  - Rats treated with temelastine (SK&F 93,944), a novel histamine H1-receptor
      antagonist, develop thyroid lesions characterized by hypertrophy and colloid
      depletion. To investigate the mechanism underlying the lesion the biliary
      clearance and hepatocellular accumulation of radio-labelled iodothyronines was
      measured in rats or cultured rat hepatocytes. Treatment with temelastine
      increased both the biliary clearance (approximately 300% of control) and
      hepatocellular accumulation (approximately 200%) of thyroxine (T4) but had little
      or no effect on tri-iodothyronine (T3). Chromatographic analysis of bile samples
      from temelastine-treated rats showed that the majority (approximately 78%) of T4
      was present in the unconjugated form. This contrasted with data from
      phenobarbitone-treated rats which showed that approximately 80% of T4 in the bile
      was present as the glucuronide conjugate. Studies with cultured hepatocytes
      showed that the hepatocellular accumulation of T4 was energy dependent. At 4
      degrees C the treatment-related increases in accumulation of T4 were abolished,
      suggesting that temelastine is specifically affecting the high affinity, energy
      dependent system which preferentially transports thyroxine into hepatocytes.
      Because temelastine is metabolized extensively, investigations were undertaken to
      discover if the hepatic effects were caused by the parent compound or an
      oxidative metabolite. The results showed that the hepatocellular accumulation of
      T4 remained increased in hepatocytes co-incubated with temelastine and 1
      aminobenzotriazole (a suicide inhibitor of cytochrome P450), even though no
      measurable P450 could be found in the cells. Also, in studies with two major
      "rat" metabolites of temelastine, i.e. 93,944-Met I or 93,944-Met VIII,
      treatments failed to reproduce the responses seen with the parent
      compound.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1980409
TI  - Bispyridinium (oxime) compounds antagonize the "ganglion blocking" effect of
      pyridostigmine in isolated superior cervical ganglia of the rat.
AB  - The "antidotal effectiveness" of several bispyridinium compounds (HGG 12, HGG 65,
      HGG 70, HI 6, HLo and HLo 12) against the acetylcholinesterase (AChE) inhibitor
      pyridostigmine was evaluated in isolated superior cervical ganglia of the rat.
      Compound action potential amplitudes were inhibited by pyridostigmine in a
      concentration-dependent manner. HI 6 and atropine proved to be the most effective
      compounds in antagonizing the "ganglion blocking" action of pyridostigmine. Their
      relative effectiveness (PE value) was 5.4 and 4.2, respectively. All of the six
      bispyridinium compounds inhibited carbachol-induced, nicotinic, ganglionic
      surface depolarizations. The antinicotinic potencies of HI 6 and HLo 7 were about
      one order of magnitude lower (apparent KI values: 294 and 330 mumol/l) than the
      antinicotinic potencies of HGG 12, HGG 65, HGG 70 and HLo 12 (apparent KI values
      ranging from 19 to 41 mumol/l). The antinicotinic potencies of the bispyridinium
      compounds did not correlate with their in vitro protection of synaptic
      transmission in sympathetic ganglia. Moreover, the effectiveness of atropine
      points to the importance of antimuscarinic properties of possible "antidotes" for
      the maintenance of ganglionic transmission in cases of AChE poisoning.

PMID- 1980410
TI  - Sensitivity of transglutaminase in rat tissues to administration of acrylamide in
      vivo.

PMID- 1980411
TI  - [The effects of constituents of an antitussive and expectorant preparation on
      physical dependence on and antitussive activity of dihydrocodeine].
AB  - The effects of constituents of an antitussive and expectorant preparation on
      physical dependence potential and antitussive activity of dihydrocodeine (DC)
      were studied. Rats were treated with DC, methylephedrine (ME), chlorpheniramine
      (CP), and caffeine (CA) singly or simultaneously admixed with food (DC 0.125, ME:
      0.25, CP: 0.05, CA: 0.25 mg /g of food) for 7 days. Subsequently, rats were
      treated with naloxone (0.5 mg/kg, sc) and withdrawal signs produced were
      observed. Naloxone-precipitated body weight loss in DC-treated rats was
      suppressed by simultaneous administration of the three drugs (ME, CP and CA) or
      CP, which is a H1-receptor antagonist. In abrupt withdrawal, the withdrawal signs
      were also suppressed by CP. Moreover, tripelennamine, the same kind of H1
      receptor antagonist, suppressed naloxone-precipitated withdrawal signs, but
      cimetidine H2-receptor antagonist, did not suppress them. These results may
      suggest that H1-receptor antagonists suppress the development of physical
      dependence on DC, and that H1-receptors play an important role in the physical
      dependence. On the other hand, the cough reflex was induced by electric
      stimulation in order to evaluate the influence of ME, CP, and CA on antitussive
      effect of DC in guinea pigs. ME enhanced the effect of DC. These experimental
      findings suggest that the constituents of the antitussive and expectorant
      preparation suppress the development of physical dependence on DC, though they
      increase the antitussive effect of DC.

PMID- 1980413
TI  - Symposium on Marine Foods, International Foundation for the Promotion of
      Nutrition Research and Nutrition Education, Knokke, September 28-29, 1989.
      Proceedings.

PMID- 1980412
TI  - H2-receptor antagonism is not pro-arrhythmic in a chronic canine model.
AB  - Seven to 28 days after coronary artery ligation, programmed electrical
      stimulation was performed in conscious dogs. Groups of 6 previously inducible
      dogs in which no arrhythmia could presently be achieved were randomly allocated
      to receive quinidine, cimetidine, ranitidine or placebo. Results were assessed
      for the drugs' ability to induce ventricular tachycardia or fibrillation, and
      compared with placebo using Fisher's Exact Test. In the placebo group 4/6 dogs
      remained unchanged, one developed an arrhythmia, and one died. With quinidine,
      3/6 dogs developed an arrhythmia (0.5 mg/kg, 4.0 mg/kg, 4.0 mg/kg) and three died
      (4 mg/kg, 8 mg/kg, 16 mg/kg) (p less than 0.05 compared with placebo). With
      cimetidine, 4/6 dogs remained unchanged, one developed an arrhythmia after 4
      mg/kg, and one died after 0.5 mg/kg. After ranitidine 3/6 dogs remained unchanged
      and three died (1.0 mg/kg, 4.0 mg/kg, 16.0 mg/kg). PR, QTc, QRS, refractory
      periods, and mean systolic pressure remained unchanged after placebo, cimetidine,
      and ranitidine, but QTc increased (p less than 0.05) and mean systolic pressure
      fell (p less than 0.01) after quinidine. Heart rate did not change following
      placebo, but increased (p less than 0.05) after each of the three drug
      treatments. These results fail to show a significant arrhythmogenic effect of
      cimetidine or ranitidine in a model validated by the significant pro-arrhythmic
      effects of quinidine. The cause of death in all cases was ventricular
      fibrillation.

PMID- 1980414
TI  - Nutritional fatty acids control. Composition and function of cerebral membranes.

PMID- 1980415
TI  - [Comparative clinical studies of oral premedication in childhood with reference
      to various pharmaceuticals].
AB  - In a randomized prospective study of 206 children aged between one and 14, the
      influence of oral praemedication on the psychic condition and with regard to
      anaesthesiologic measures was investigated. Heart rate, inhibition of salivation
      and the kind and frequency of side-effects were also examined. The praemedication
      was carried out using diazepam (0.3 mg/kg), promazin (1.0 mg/kg), promethazin
      (1.0 mg/kg) and chlorphenaethazin (1.0 mg/kg). It was not possible to determine
      statistically relevant differences between the various drugs concerning the fixed
      criteria. In general, however, diazepam seems to achieve the best results. In the
      younger children (1 to 6 years) a frequent and insufficient effect of
      praemedication was noted immediately. Oral praemedication proved to be a valuable
      and practicable method which was well tolerated by the great majority of the
      children.

PMID- 1980417
TI  - Chaperone function: the assembly of ribulose bisphosphate carboxylase-oxygenase.

PMID- 1980416
TI  - Amino acid sequence of the acidic Kunitz-type trypsin inhibitor from winged-bean
      seed [Psophocarpus tetragonolobus (L.) DC].
AB  - The primary sequence of trypsin inhibitor-2 (WBTI-2) from Psophocarpus
      tetragonolobus (L.) DC seeds was determined. This inhibitor consists of a single
      polypeptide chain of 182 amino acids, including four half-cystine residues, and
      an N-terminal residue of pyroglutamic acid. The sequence of WBTI-2 showed 57%
      identity to the basic trypsin inhibitor (WBTI-3) and 50% identity to the
      chymotrypsin inhibitor (WBCI) of winged bean, and 54% identity to the trypsin
      inhibitor DE-3 from Erythrina latissima seed. The similarity to the soybean
      Kunitz trypsin inhibitor (40%) and the other Kunitz-type inhibitors from
      Adenanthera pavonina (30%) and wheat (26%) was much lower. Sequence comparisons
      indicate that the Psophocarpus and Erythrina inhibitors are more closely related
      to each other than to other members of the Kunitz inhibitor family.

PMID- 1980418
TI  - The synapsins.

PMID- 1980420
TI  - Dracunculiasis.

PMID- 1980419
TI  - Nerve growth factor synthesis and its regulatory mechanisms: an approach to
      therapeutic induction of nerve growth factor synthesis.
AB  - Nerve growth factor (NGF) is a protein necessary for the differentiation and
      maintenance of peripheral sympathetic neurons, certain sensory neurons, and
      cholinergic neurons of the basal forebrain. NGF is synthesized in target areas of
      NGF-responsive neurons. This protein binds to specific cell surface receptors on
      the nerve terminals and is retrogradely transported to the cell bodies of the
      neurons, during which various physiological functions are expressed. In spite of
      its physiological importance, the regulatory mechanisms of NGF synthesis are
      unknown. We approached this problem from an in vitro cellular aspect and in turn
      applied the knowledge obtained to in vivo studies on the regulation of NGF
      synthesis. Nonneuronal cells, such as astroglial cells, fibroblast cells, and
      Schwann cells, synthesize and secrete NGF in cultures. NGF synthesis by these
      cells is growth dependent, suggesting that the expression of some genes relevant
      to cell growth is associated with upregulation of NGF synthesis. To elucidate
      neuronal influences, we tested various neurotransmitters and found that
      catecholamines and their analogues have stimulatory effects on NGF synthesis of
      nonneuronal cells. From the results of a structure-activity relationship,
      alkylcatechol compounds with an alkyl group at position 4 of the catechol ring
      show a potent stimulatory activity in vitro. Evidence that NGF has a potent
      protective activity on neuronal degeneration both in the central nervous system
      (CNS) and peripheral nervous system (PNS) is accumulating. NGF is a macromolecule
      that cannot pass through the blood-brain barrier, suggesting a limited
      availability of this protein for therapeutic use in diseases with neuronal
      degeneration in the CNS. We considered that compounds with a low molecular weight
      that elicit stimulatory activity on NGF synthesis are much more useful and
      practical for therapeutic purposes. Therefore, we investigated alkylcatechol
      compounds and their diacetyl derivatives, and found them to be able to induce NGF
      synthesis in the rat PNS in vivo. This is the first step in developing an agent
      capable of inducing NGF synthesis for therapeutic use in the future. The
      physiological and/or therapeutic significance of NGF induction is discussed.

PMID- 1980421
TI  - The management of cardiac arrhythmias: The role of encainide and sotalol. A
      symposium. March 24-25, 1988. Proceedings.

PMID- 1980422
TI  - Beta-phenylethylamine (PEA): an endogenous anxiogen? Three series of experimental
      data.
AB  - Like the anxiogenic drugs caffeine, pentylenetetrazole, and yohimbine, the
      endogenous neuroactive monoamine beta-phenylethylamine (PEA) is effective in
      three tests for anxiogens in mice. In a social interaction test it reduced both
      the number and duration of contacts. In a conflict situation test (a dark-light
      chamber) it reduced the number of transitions between dark and light
      compartments. Diazepam, a standard anxiolytic, prevented both effects of PEA.
      Intracerebroventricular administration of PEA induced generalized clonic seizures
      which were antagonized by various anxiolytics but not by the tested doses of
      butyrophenone neuroleptics and standard anticonvulsants effective in other tests
      for convulsants.

PMID- 1980423
TI  - Conformational study of a somatostatin analogue in DMSO/water by 2D NMR.

PMID- 1980424
TI  - Structural and functional characterization of the mouse multidrug resistance gene
      family.
AB  - The mouse multidrug resistance (mdr) gene family is composed of three closely
      related genes mdr1, mdr2 and mdr3. To clarify the role of these three genes in
      the emergence of multidrug resistance and to initiate a structure-function
      analysis of the corresponding proteins, we have isolated full length cDNA clones
      corresponding to their respective cellular RNA transcripts. Sequence analyses
      indicate that the three encoded polypeptides are highly similar sharing the same
      predicted structural features and a high degree of sequence homology (85% to
      92%). The three genes are contiguous on a 625 kb chromosomal segment and appear
      to result from two consecutive gene duplication events. Hybridization studies
      with gene specific probes in independently derived multidrug resistant cell lines
      and transfection experiments with full length cDNA clones indicate that mdr1 and
      mdr3 but not mdr2 overexpression can induce multidrug resistance. In transfected
      cells, multidrug resistance is linked to a decreased drug accumulation and an
      concomitant increased ATP-dependent drug efflux. Mutational analysis indicates
      that both predicted ATP binding domains in mdr1 are absolutely essential for
      biological activity. The study of chimeric proteins constructed between
      biologically active mdr1 and inactive mdr2 indicate that both ATP binding domains
      of mdr2 are functional and suggest that transmembrane domains of mdr1 are
      essential for the drug resistance phenotype conferred by this protein. Finally,
      although mdr1 and mdr3 can confer multidrug resistance, drug survival
      characteristics of mdr1 and mdr3 transfectants indicate that both proteins have
      overlapping but distinct substrate specificities.

PMID- 1980425
TI  - Strategies to circumvent multidrug resistance due to P-glycoprotein or to altered
      DNA topoisomerase II.
AB  - Strategies to circumvent different forms of multidrug resistance (MDR) in tumor
      cells will be discussed. The form of MDR associated with overexpression of P
      glycoprotein. Pgp-MDR, is well-understood, and its features are briefly
      described. Many clinically useful lipophilic organic bases have been shown to
      interfere with drug efflux mediated by Pgp, consequently circumventing or
      overcoming this form of MDR. Based on these empiric observations, screening and
      molecular modeling efforts are being employed to develop new modulators of Pgp
      MDR. However, because inhibition of normal tissue Pgp can cause unacceptable
      toxicities, new strategies to circumvent Pgp-MDR in tumors must be sought.
      Possibilities range from pharmacokinetic modeling to the development of tissue
      specific inhibitory antibodies or antisense oligonucleotides. Tumor cells
      expressing altered DNA topoisomerase II express a more restricted form of MDR,
      termed at-MDR, that will be discussed briefly and compared with Pgp-MDR.
      Modulators of Pgp-MDR are without effect in cells expressing only at-MDR.
      However, some analogs of anthracyclines appear to act via a topo II-independent
      pathway and can circumvent this form of resistance. Also, alterations in
      topoisomerase II may have consequences for other cellular functions, as at-MDR
      cells appear to have defects in DNA repair pathways, suggesting other areas for
      therapeutic exploitation.

PMID- 1980426
TI  - Salmeterol.

PMID- 1980427
TI  - [Microsurgical repair of heel and sole defects].
AB  - Since 1984, microsurgical technique has been applied to reconstruct and repair
      the defects of heel and sole in 21 cases by replantation and implantation. Among
      them, 12 cases were heel defects, 3 cases were fore-sole defects and 6 cases were
      complete sole defects. Emergency repair and reconstruction has been performed in
      13 cases and late reconstruction in 8 cases. All flaps survived. Our main
      experiences were: 1. All sorts of defected tissues should be reconstructed at the
      same time. 2. The selection of donor area should be according to the
      principles:lateral or medial leg flap should be used for moderate defects;
      lateral thoracic flap for large defects; and the flap of center sole for small
      defects. 3. Debridement of focus should be done thoroughly.

PMID- 1980428
TI  - Phencyclidine and related compounds evoked [3H]dopamine release from rat
      mesencephalic cell cultures by a mechanism independent of the phencyclidine
      receptor, sigma binding site, or dopamine uptake site.
AB  - At concentrations greater than or equal to 100 microM, phencyclidine (PCP), N-(1
      (2-thienyl)-cyclohexyl)piperidine (TCP), and MK-801 induced [3H]dopamine release
      from dissociated cell cultures of rat mesencephalon. This release was Ca2+
      independent and tetrodotoxin insensitive. Tetrodotoxin (2 microM) itself had no
      effect on spontaneous release of [3H]dopamine. [3H]Dopamine release was induced
      by 1,3-di(2-tolyl)guanidine, a sigma ligand, and by 4-aminopyridine (1-3 mM), a
      K+ channel blocker. No stereoselectivity was observed for [3H]dopamine release
      evoked by the dioxadrol enantiomers, dexoxadrol, and levoxadrol, or by
      enantiomers of N-allylnormetazocine (SKF 10,047). The selective dopamine uptake
      inhibitor 1-(2-[bis(4-fluorophenyl)methoxy]ethyl)-4-(3-phenylpropyl)piperazine
      dihydrochloride (GBR 12909) did not affect spontaneous or TCP-evoked [3H]dopamine
      release. Together, these data suggest that the dopamine-releasing effects of PCP
      like compounds on the mesencephalic cells were not mediated by actions at the PCP
      receptor or sigma binding site, Ca2+, or Na+ channels, or at the high affinity
      dopamine uptake site. It remains conceivable that blocking actions of PCP-like
      compounds at voltage-regulated K+ channels may at least partly explain the
      response. These results are discussed in comparison with findings in intact
      brain.

PMID- 1980430
TI  - Acute dystonic reaction in normal humans caused by catecholamine depletion.
AB  - Five of 24 (21%) normal men (volunteers) administered alpha-methyl-para-tyrosine
      (AMPT), a catecholamine-depleting agent, developed acute dystonic reactions. The
      finding that catecholamine depletion without receptor blockade is sufficient to
      cause acute dystonia suggests that a variety of neurotransmitter imbalances may
      lead to idiopathic primary dystonia.

PMID- 1980429
TI  - Reexamination of dopamine as the prolactin-release inhibiting factor (PIF):
      supplementary agent may be required for dopamine to function as the physiological
      PIF.
AB  - A large number of studies have been performed concerning dopamine's inhibitory
      effect on prolactin release, but many of these studies have examined the effect
      of dopamine dissolved in a solution containing ascorbic acid. Ascorbic acid,
      routinely used to protect dopamine from oxidation, alone does not stimulate or
      inhibit prolactin release, but it can potentiate the inhibitory effect of
      dopamine in a static monolayer culture system by approximately 100 times. We have
      closely examined the inhibitory effect of dopamine on prolactin release in the
      absence of ascorbic acid using a perifusion system. Male rat adenohypophyses were
      dispersed with trypsin and cultured in a Petri dish to form cell clusters.
      Inhibition of prolactin release by dopamine (1 mumol/L) in the absence of
      ascorbic acid was sustained for only 63 min during the 2-h perifusion period.
      Following a 2-h period of incubation of dopamine in the same experimental
      solution, the dopamine concentration was reduced from 1 to 0.18 mumol/L, yet this
      "2-h-old dopamine" was still effective in inhibiting prolactin release
      (approximately 30 min). This result suggests that the lactotrophs may be
      desensitized by chronic exposure to a high concentration of dopamine in the
      absence of ascorbic acid. In contrast, when a low concentration of dopamine (3
      nmol/L) containing ascorbic acid (0.1 mmol/L) was perifused, inhibition of
      prolactin release was sustained for the entire 2-h perifusion period. Although
      there may be a large number of explanations for dopamine's transient inhibitory
      effect on prolactin release, the present results suggest that dopamine may
      require supplementary agent(s) to effectively inhibit prolactin release and thus
      function as the prolactin release inhibitory factor (PIF).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1980431
TI  - [Influence of microinjection of dynorphin antibody into periaqueductal gray (PAG)
      on analgesia induced by electroacupuncture of different frequencies in rats].
AB  - Previous studies have shown that 2 Hz but not 100 Hz electroacupuncture (EA)
      stimulation released beta-endorphin in PAG of the rat to induce analgesia. The
      present study was undertaken to see whether dynorphin plays a role in PAG in
      mediating analgesia induced by low and high frequency EA. Injection of affinity
      purified dynorphin antibody (1:350,000 in RIA titer) 1 microliter into PAG
      blocked 2 Hz EA analgesia almost completely, and 15 Hz EA analgesia partly,
      leaving 100 Hz EA analgesia intact. This blocking effect was totally disappeared
      when the antibody was diluted to 1/10 of its original concentration (1:35,000).
      Besides, injection of dynorphin into PAG through chronically implanted cannula
      showed no analgesic effect. The results suggest that the blockade of 2 Hz EA
      analgesia by high titer dynorphin antibody injected into PAG may have been the
      result of cross reactivity of the antibody to other opioid peptides (such as beta
      endorphin, enkephalin, etc) released in the PAG area. The data also stress the
      importance of using antibodies of proper titer and concentration to exclude false
      positive or false negative conclusions in adopting the antibody microinjection
      techniques, as was repeatedly shown in the immunohistochemical studies.

PMID- 1980432
TI  - [Experiment research on moxibustion treating infected EHFV rat].
AB  - In this experiment, we established a rat model of EHFV infected by abdominal
      cavity, and observed the effect of moxibustion on the changes of antigens,
      antibodies, neural transmitters in blood and tissue on 60 weanling Wistar rats
      with EHF. The rats were divided into three groups: normal control group (N.
      group), EHF control group (C. group) and EHF with moxibustion group (M. group) at
      random. Moxibustion was given at "Shenshu" for 30 minutes daily, 7 days. The 14th
      day after infection of EHFV, blood and lungs of the rats were fetched. The
      results obtained are as follows: 1. The effect value of EHF antibodies dilution:
      in C. group, it is 1:267 +/- 82 (n = 8), in M.group, it is 1:336 +/- 176 (n =
      10), there is a significantly different of specific antibodies between C.group
      and M.group. The results show that moxibustion had an effect of enhancing the
      function of immune system in rats with EHF. 2. The examination rate of EHFV
      antigens in lungs, in C.group, it is 62.5% (n = 8), in M.group, it is 49.4% (n =
      16). The results show that moxibustion may enhance the immune function and the
      effect of eliminating virus of lymphocytes in lungs. 3. The value of BUN in
      serum: in N.group, it is 15.3 +/- 2.50 (n = 10), in C.group, it is 24.63 +/- 7.24
      (n = 10), and in M.group, it is 16.36 +/- 4.59 (n = 26). There is a significantly
      different between C.group and N.group or M.group (P less than 0.001). There is no
      significantly different between N.group and M.group (P greater than
      0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1980433
TI  - Effects of humoral factors in viscera-auriculopoint response in rabbits--a cross
      circulation experiment.

PMID- 1980434
TI  - Neurotoxins from venoms of the Hymenoptera--twenty-five years of research in
      Amsterdam.
AB  - 1. In co-operation with colleagues in Europe, Japan and the U.S.A., 25 years of
      research in Amsterdam have provided new views on the way some hymenopteran
      insects incapacitate their prey by a diversity of neurotoxins, resulting in block
      of synaptic transmission in CNS or neuromuscular junctions, or affecting voltage
      dependent phenomena in nerve and muscle fibers. 2. Nicotinic synaptic
      transmission in the insect CNS is irreversibly blocked at the presynaptic side by
      kinins, or reversibly and postsynaptically blocked by philanthotoxins. 3.
      Glutamatergic neuromuscular transmission is reversibly blocked by philanthotoxins
      at the pre- and/or postsynaptic side. 4. A presynaptic block of neuromuscular
      transmission was found with the Microbracon toxins. 5. An irreversible
      deactivation, without paralysis, of cockroaches is caused by a sting of Ampulex
      compressa into the suboesophageal ganglion. 6. Poneratoxin, a 25 amino acid
      residue polypeptide, isolated from an ant venom, is the first described
      hymenopteran neurotoxin affecting excitability of nerve and muscle fibres by
      changing the kinetics of the voltage-dependent sodium channel.

PMID- 1980435
TI  - Possibility of anti-estrogen action from estriol specific binding sites in rabbit
      uterus.
AB  - 1. This study was designed to investigate the clomiphene or tamoxifen binding to
      receptor sites for estradiol-17 beta (E2R) and estriol (E3R) in the rabbit
      uterus. 2. Those so-called anti-estrogenic compounds tended to inhibit E2-E2R and
      E3-E3R bindings equally. 3. The inhibitor constant of clomiphene for E2R was
      approximately 3.8 x 10(-8) M at 4 degrees C and that for E3R approximately 1.8 x
      10(-8) M at 4 degrees C in a given case, determined by charcoal assay. 4. It is
      suggested that the anti-estrogenic compounds demonstrate their effects after
      binding either to E2R or to E3R. 5. There were some tissue differences of the
      contents between E2R and E3R. For example, the uterus and the cortex contained
      E2R, and the pituitary E3R more than the other.

PMID- 1980436
TI  - Adaptive changes of H+ secreting cells in the epidermis of the leopard frog Rana
      pipiens.
AB  - 1. Mitochondria-rich (MR) cells in the integument of the southern leopard frog,
      Rana pipiens, berlandieri, were stained with AgNO3 under a variety of
      environmental and metabolic treatment conditions known to increase H+ excretion
      rates across the skin. In this tissue AgNO3 proved to be a good stain for
      discriminating the MR cell populations from the granular cells. 2. High salinity
      adapted southern frogs showed no change in the MR cell population. The inability
      of the MR cell number to significantly increase suggested that the increased H+
      excretion rates previously seen in these animals were not due to increased MR
      cell proliferation. 3. The MR cell population was found to increase in the NaNO3
      adapted frogs, demonstrating the contribution of altered extracellular Cl-
      concentrations on the regulation of MR cell density. 4. Animals that were placed
      in chronic metabolic acidosis or pre-treated with ibuprofen demonstrated an
      increased MR cell population. The current observations are consistent with
      previous findings that these treatment regimes increase H+ excretion, suggesting
      that one of the cellular adaptive mechanisms responsible for increasing H+
      excretion involves increasing the MR cell density. 5. The results further suggest
      that prostaglandins may play a role in regulating H+ excretion in MR cells, and
      that either changes in intracellular pH or prostaglandin formation regulates cell
      proliferation.

PMID- 1980437
TI  - A comparison of hepatic P450 induction in rat and trout (Oncorhynchus mykiss):
      delineation of the site of resistance of fish to phenobarbital-type inducers.
AB  - 1. A comprehensive approach was taken to delineate the site of refractivity of
      trout to phenobarbital-type (PB-type) hepatic monoxygenase (MO) inducers. 2.
      Model inducers beta-naphthoflavone (BNF; 3-MC-type), and PB as well as the
      polychlorinated biphenyl isomers, 3,4,5,3',4',5'-hexachlorobiphenyl (3,4,5-HCB; 3
      MC-type) and 2,4,5,2',4',5'-hexachlorobiphenyl (2,4,5-HCB; PB-type) were used to
      assess MO activities, total cytochromes P450, and [35S]-methionine incorporation
      into de novo synthesized microsomal protein in both trout and rats. 3. In rainbow
      trout immunodetection of P450 isozymes and nucleic acid hybridization of rainbow
      trout P(1)450 mRNA using pfP(1)450-3' (trout 3-MC-inducible, P450IA1 gene) and
      genomic DNA using pfP(1)450-3' or pSP450-oligo (rat PB-inducible, P450IIB1 gene)
      cDNAs were carried out. 4. In rainbow trout, PB and 2,4,5-HCB do not increase
      hepatic MO activities, total cytochromes P450, de novo synthesis of microsomal
      protein, levels of P450 isozymes, or levels of P(1)450 mRNA. 5. Rainbow trout
      have, within their genome, DNA with sequence(s) similar to rat P450IIB1, but
      inducibility of this P450 in trout by PB-type inducers is lacking.

PMID- 1980438
TI  - Relationship between selenium, immunity and resistance against infection.
AB  - 1. Food selenium content, selenium supply and selenium needs are presented, along
      with methods of evaluation of selenium status. Glutathione peroxidase, a selenium
      containing enzyme, is ubiquitous in the organism. 2. Some experimental studies on
      animal models reported a positive relationship between selenium status and
      resistance against infections. 3. Only one study in humans concerned the
      mechanisms of immune functions in selenium deficiency. Several experimental works
      suggest that severe selenium deficiency compromises T-cell dependent immune
      functions such as the blastogenic response to mitogens, but selenium deficiency
      was concomitant with vitamin E deficiency in most of them. Delayed
      hypersensitivity response is controversial in selenium-supplemented rats and
      guinea-pigs. 4. Selenium deficiency in animals decreases the antibody response,
      especially if associated with vitamin E deficiency. Low dietary selenium
      supplementation of healthy animals has a positive effect upon humoral responses.
      5. Despite some controversies, most experimental studies on selenium-deficient
      animals report normal phagocytosis and an altered bactericidal capacity of
      neutrophils. The decrease in glutathione peroxidase activity of polymorphonuclear
      cells following selenium deficiency could explain some of these alterations. 6.
      Splenic Natural Killer cells activity is enhanced in selenium-supplemented,
      healthy animals.

PMID- 1980439
TI  - Neuronal uptake of noradrenaline in the rat isolated trachea: effect of ageing.
AB  - 1. The neuronal uptake of 3H-noradrenaline in isolated trachea strips of the rat
      was analysed from cocaine-resistant 2 min accumulation of 3H-noradrenaline from
      reserpine pre-treated animals. 2. Neuronal uptake of 3H-noradrenaline was
      demonstrated to exist in isolated trachea of rats at different ages (4, 12 and 20
      months old). 3. The determination of kinetic parameter values (Vmax and apparent
      Km) of neuronal 3H-noradrenaline uptake indicated that this transport process was
      not modified by ageing.

PMID- 1980440
TI  - Demyelinisation in the spinal cord of vitamin B12 deficient fruit bats.
AB  - 1. Vitamin B12 deficiency induced in the fruit bat by a combination of dietary
      deprivation and exposure to nitrous oxide (N2O) is accompanied by profound
      neurological impairment, thus providing an experimental model for the study of
      vitamin B12 neuropathy. 2. Electron microscopy of the spinal cord of vitamin B12
      deficient bats shows marked changes in the myelin of the posterior columns in the
      form of distension, separation and vacuolation of myelin lamellae similar to the
      changes described in the dietary induced B12 deficient monkey model. 3. No
      equivalent change occurred in bats exposed to N2O and supplemented with vitamin
      B12.

PMID- 1980441
TI  - Brain amines and neocortical EEG in young and aged rats.
AB  - 1. Frontal and parieto-occipital electroencephalography (EEG) of young (4 months
      old) and aged (17 and 22 months-old) Wistar rats were analyzed, both during
      movement and during waking immobility. 2. The levels of monoamines, serotonin and
      their metabolites were measured from the frontal cortex, parieto-occipital
      cortex, hippocampus, brainstem and midbrain. 3. In aged rats, as compared to
      young rats, the most apparent changes of the quantitative EEG spectrum were the
      decreased amplitude of alpha (5-10 Hz) and beta (10-20 Hz) frequency bands in the
      frontal and parieto-occipital cortices during both movement and waking immobility
      behavior (p less than 0.05). 4. The levels of dopamine (DA), homovanillinic acid
      (HVA), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) or the ratios of 5
      HT/5-HIAA and DA/HVA did not differ between young and aged rats in any brain
      region studied, with the exceptions of brainstem DA and parieto-occipital 5-HIAA,
      which were elevated in aged rats (p less than 0.05). 5. In the frontal cortex,
      hippocampus and midbrain, noradrenaline (NA) levels of aged rats were slightly
      increased as compared to young rats (p less than 0.05). 6. NA levels of the
      parieto-occipital cortex and brainstem did not change during aging. 7.
      Furthermore, there were no clear correlations between the decreased amplitude of
      the quantitative EEG spectrum and monoamine or serotonin concentrations, or the
      ratios of 5-HT/5-HIAA and DA/HVA in the cerebral cortex of aging Wistar
      rat.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1980442
TI  - Isolation of geodiatoxins 2-4 from the marine sponge Geodia mesotriaena.
AB  - 1. In a previous study of the marine sponge Geodia mesotriaena von Lendenfeld for
      antineoplastic constituents, evidence was obtained for the presence of several
      toxins and geodiatoxin 1 was isolated. 2. Further separations guided by bioassay
      using CDF1 mice have led to the isolation of three additional chromoprotein
      toxins lethal at 8 mg/kg.

PMID- 1980443
TI  - Effect of cefatrizine and cephaloglycine on L-leucine absorption in rat jejunum.
AB  - 1. The oral cephalosporins: cefatrizine and cephaloglycine inhibit the L-leucine
      absorption in vivo on rat jejunum. 2. This inhibition is dose and time dependent
      and the effect is irreversible. 3. These antibiotics have a systemic effect on L
      leucine absorption. 4. The inhibition of these antibiotics affect only leucine
      transport, without affecting the diffusion. 5. Cefatrizine and cephaloglycine
      inhibit the basolateral (Na(+)-K+) ATPase activity in rat jejunum.

PMID- 1980444
TI  - The distribution of calmodulin in the mucosa of the avian oviduct and the effect
      of p-p'-DDE on some of its metabolic parameters.
AB  - 1. Since calmodulin or some closely related peptide may activate the Ca2(+)
      transporting system in the avian eggshell gland, the calmodulin content in
      different parts of the oviduct mucosa was determined in egg-laying birds killed
      at 1600 hr. 2. The highest content was noted in the shell gland mucosa both in
      egg-laying ducks and hens. The calmodulin content was high even in the isthmus
      part, where the shell formation begins. 3. Treatment of ducks (Indian runner
      variety) with DDE (40 ppm for 45 days) did not influence the calmodulin content
      of the shell gland, however. 4. The content of the protein avidin, the formation
      of which is stimulated by progesterone, was increased significantly in the
      oviduct. The carbanhydrase activity did not change significantly. 5. The dry
      weight of the shell gland was reduced by DDE administration in ducks but not in
      domestic fowls. 6. These and earlier observations indicate that DDE can act as an
      partial agonist which is able both to stimulate and to inhibit reactions in the
      shell gland and other parts of the oviduct. 7. In vivo DDE in the dose used
      probably acted on higher centres, influencing the activity of the shell gland and
      probably other parts of the oviduct. 8. A regulation centre which influences
      several sexual functions is the hypothalamic-hypophyseal region, but the
      endocrine function of the ovary has also been considered.

PMID- 1980445
TI  - Depuration kinetics of hexachlorobenzene in the clam, Macoma nasuta.
AB  - 1. The depuration rate constant for [14C]hexachlorobenzene (HCB) in the clam,
      Macoma nasuta, was determined following a short-term exposure to HCB contaminated
      seawater. 2. Depuration was not correlated with ventilation volume, nor did the
      amount of sediment ingested during depuration have a significant effect. 3. The
      half-life for HCB in M. nasuta was estimated to be 16 days with a
      bioconcentration factor of 3490 (wet weight basis).

PMID- 1980446
TI  - Antihypertensive effect of tryptic hydrolysate of milk casein in spontaneously
      hypertensive rats.
AB  - 1. Repeated oral administrations of tryptic hydrolysate of bovine milk casein
      (CEI) showed antihypertensive effect in spontaneously hypertensive rats. 2.
      Single oral administration of CEI antagonized the pressor response to angiotensin
      I. 3. Bovine milk casein hydrolysate inhibited the angiotensin I-converting
      enzyme (ACE) activity. Three peptides with ACE-inhibiting activity were isolated
      from CEI. 4. It is suggested that ACE-inhibiting peptides in the tryptic
      hydrolysate milk casein are absorbed from the intestinal tract and produce an
      antihypertensive effect.

PMID- 1980447
TI  - Beta-endorphin-like and adrenocorticotropin-like materials in turtle heart and
      intestine.
AB  - 1. Turtle heart and intestine acetone powders were extracted with an acetone
      water-HCl mixture. An acid acetone powder resulted by adding a copious volume of
      acetone to the extract. The powder was subjected to gel filtration on Sephadex G
      25 and ion exchange chromatography on CM-cellulose. 2. In turtle heart,
      corticotropin-like bioactivity was distributed among chromatographic fractions
      (derived from material unretarded on Sephadex G-25) unadsorbed and adsorbed on CM
      cellulose. The highest opiate receptor binding activity and beta-endorphin-like
      immunoreactivity were adsorbed on CM-cellulose. 3. In turtle intestine,
      corticotropin-like bioactivity was absent. Opiate receptor binding activity was
      present in fractions unretarded as well as in fractions retarded on Sephadex G
      25, indicating a molecular weight of greater and smaller than 5000 respectively.
      4. The highest opiate receptor binding activity and beta-endorphin-like
      immunoreactivity were found in a fraction adsorbed on CM-cellulose.

PMID- 1980448
TI  - Behavioral genetic analysis of regional mouse brain biogenic amines, acidic
      metabolites and motor activity.
AB  - 1. Comparative analyses of regional brain biogenic amines and spontaneous
      locomotor activity of three mouse strains suggest a genotype dependent
      relationship. 2. A positive correlation between striatal dopamine and locomotor
      activity was determined in the inbred albino BALB/c mouse strain. 3. An inverse
      relationship between some brain regions serotonin and motility was found in the
      inbred black C57BL/6 mouse strain. 4. No correlation could be established between
      brain monoamines and motor activity in the hybrid CDF-1 mouse strain. 5. The
      results suggest that inbred BALB/c and C57BL/6 mouse strains may be useful animal
      models for studying dopaminergic and serotonergic acting agents, respectively.

PMID- 1980449
TI  - Effects of sodium and temperature on naloxone binding in brain tissues of a
      urodele amphibian.
AB  - 1. Partially purified brain membranes obtained from male rough-skinned newts
      (Taricha granulosa) were used to determine the effects of NaCl and temperature on
      the specific binding of the opioid receptor antagonist [3H]naloxone. 2. The
      addition of NaCl to the incubation medium at concentrations up to 400 mM produced
      a dose-related increase of the specific binding of [3H]naloxone. 3. The addition
      of other salts to the incubation medium had less pronounced effects: KCl and
      MgCl2 slightly increased and decreased, respectively, the specific binding of
      naloxone, and CaCl2 had no effect. 4. Results of an equilibrium saturation
      experiment showed that the addition of 200 mM NaCl resulted in over a 10-fold
      increase in the number of high affinity (KD = 0.61 nM) binding sites for
      naloxone, with no changes in the number of low affinity (KD = 21.8 nM) binding
      sites. 5. Changes in NaCl concentrations did not significantly affect either
      dissociation constant. 6. The binding of [3H]naloxone was temperature-dependent;
      it increased when the incubation temperatures were elevated from 0 degree C to 37
      degrees C. 7. Results obtained for this urodele amphibian are compared with those
      available for other vertebrate species.

PMID- 1980450
TI  - Glucagon and insulin responses to alpha-adrenergic subtype receptor blockade in
      sheep.
AB  - 1. Five sheep were used to investigate the influences of alpha-adrenergic subtype
      receptor blockade on the secretion of both glucagon and insulin. 2. The glucagon
      secretion was stimulated through an alpha 2-adrenergic subtype mechanism. 3. The
      secretion of insulin was inhibited by an alpha 2-adrenergic subtype mechanism in
      conscious sheep.

PMID- 1980451
TI  - The effect of alpha blockade on iontophoresis-induced ocular shedding of latent
      HSV-1 W in different host animals.
AB  - Previous studies demonstrated that non-specific beta blockade promoted ocular
      shedding of latent HSV-1 in the mouse and rabbit iontophoresis models. The
      present study examined the effect of topical alpha blockers, thymoxamine and
      corynanthine, on reactivation and induced ocular shedding of latent HSV-1 W in
      different host animals. Latent trigeminal ganglionic infection was established in
      Balb/c mice and New Zealand rabbits following corneal inoculation with HSV-1 W
      strain, and later confirmed by co-cultivation. Treatment with coded eye drops
      (thymoxamine, corynanthine or BSS was begun one day prior to iontophoresis
      induction and continued BID OU for 5 days. Reactivation and recovery of latent
      HSV-1 was determined by daily ocular swabs, and characteristic HSV-1 cytopathic
      effect in Vero cells. In Balb/c mice, topical administration of thymoxamine 0.5%
      or corynanthine 5% significantly reduced the number of virus-positive eyes, virus
      positive mice, and total virus-positive swabs per experiment, whereas the
      inhibitory effect was minimal in NZ rabbits. We conclude that alpha blockade may
      alter the reactivation signal that is mediated via the adrenergic system, and
      that different host factors (as expressed in different species) may play an
      important role in this process.

PMID- 1980452
TI  - Contact lens surface deposits increase the adhesion of Pseudomonas aeruginosa.
AB  - Soft contact lenses are bathed with tear components during wear and surface
      deposits accumulate. This report shows that Pseudomonas aeruginosa adheres to the
      surface of worn extended wear contact lenses in direct proportion to the amount
      of lens surface deposits as determined by the Rudko method (P less than .05).
      More hydrophobic bacteria adhered 10 times greater than bacteria which were
      relatively hydrophilic (P less than .005). The effect upon bacterial adhesion of
      enzyme and surfactant cleaning of worn extended wear contact lenses was
      investigated by two independent methods: one involving a high inoculum and the
      other a low inoculum of Pseudomonas. Treatment of worn lenses with commercially
      available enzymes such as papain and pork pancreatin as well as treatment with
      neuraminidase, mannosidase, glucosidase and alkylcarboxylic acid for as long as
      48 hours failed to reduce subsequent bacterial adhesion in both the high and low
      inoculum experiments. We conclude that soft contact lens surface deposits are a
      major determinant in the adhesion of Pseudomonas aeruginosa to the worn lens
      surface and that enzyme cleaning of worn lenses does not significantly reduce
      bacterial adhesion.

PMID- 1980453
TI  - Treatment of NIDDM with insulin agonists or substitutes.
AB  - Non-insulin-dependent diabetes mellitus (NIDDM) is a common disorder occurring in
      3-6% of adults in most western populations. In the United States, 29% of patients
      with diabetes take insulin; of these, 76% have NIDDM. Insulin therapy is usually
      required at some time in NIDDM. Insulin therapy improves the abnormalities of
      NIDDM (reduced beta-cell function, increased hepatic glucose production, reduced
      peripheral glucose disposal, lipid abnormalities). Insulin and sulfonylurea
      agents have comparable effects on mild forms of NIDDM, but for more severe forms,
      insulin is usually superior. Combination insulin-sulfonylurea treatment may
      improve the response to sulfonylureas, although long-term well-controlled trials
      have not been conducted. Short-term insulin treatment may restore response to
      sulfonylureas. Other promising treatments (human proinsulin, nasal insulin,
      somatostatin) have not shown any advantage over conventional insulin therapy.
      Insulin causes hypoglycemia and peripheral hyperinsulinemia. The hazards of
      hyperinsulinemia, e.g., weight gain and hypoglycemia, have been overstated, and
      questions about its atherogenic effects remain to be resolved. The effect of
      glycemic control on macro- and microvascular complications has not been
      established; however, maintaining fasting blood glucose levels of less than 6.7
      mM may protect against progression of retinopathy, neuropathy, and nephropathy
      and reduce the severity of ischemic stroke. Dosage algorithms generally use
      intermediate- or long-acting insulin to control basal glycemia, with regular
      insulin added before meals if needed to control postprandial glycemia. Effective
      therapy depends on the patient being informed, cooperative, and willing to self
      monitor blood glucose. Insulin treatment intermittency increases the risk for
      immune complications (resistance and allergy). Overall, patients with NIDDM can
      benefit from insulin therapy.

PMID- 1980454
TI  - Changes in [K+]0 at the vitreal surface compared with those around receptors in
      the isolated rabbit retina.
AB  - Isolated rabbit retinas were superfused from the receptor side with a plasma
      saline mixture kept at 35 degrees C. The vitreal side was exposed to an
      atmosphere of humidified warm oxygen. In one study the second-order neuronal
      activity was suppressed with aspartate and glutamate; in another study
      transmission was not blocked. When all neurons were active, [K+]0 around
      receptors was 4.5 +/- 0.4 mM in the dark. During a long (60s) exposure to light
      stimulus, [K+]0 dropped to 73% of the dark value and reaccumulated to 80%. At the
      vitreal surface, [K+]0 in the dark was 4.7 +/- 0.8 mM. During the 60s light
      stimulus, [K+]0 increased transiently, dropped to 83% of the dark value, then
      increased again to 91%. A continuous decrease of [K+]0 at the vitreal surface
      during long light stimuli concurrent with the increase of [K+]0 around receptors
      would indicate that the spatial buffering capability of the Muller cells
      contributes to the reaccumulation of potassium. Such a decrease, however, was not
      detected. After the blockage of transmission, [K+]0 values did not vary
      significantly from those after light stimulus in unblocked preparations. In the
      dark, [K+]0 was 5.2 +/- 0.9 mM at the vitreal surface and 4.6 +/- 0.4 mM around
      the receptors.

PMID- 1980455
TI  - Interactions of cryptosin with mammalian cardiac beta-adrenoceptors.
AB  - Cryptosin - a new cardenolide from the leaves of Cryptolepis buchanani R & S was
      found to be a potent positive inotropic agent. In experiments with dog heart ex
      vivo, the rise in the cardiac rate associated with an increase in dP/dtmax and
      left ventricular pressure (LVP) correlated with changes in the beta-adrenoceptor
      densities as measured by the binding of 3H-Dihydroalprenolol (DHA). A significant
      change in the beta-adrenoceptor densities was observed when cryptosin was
      incubated with guinea pig and dog heart sarcolemmal membranes in vitro. Analysis
      of the binding of 3H-DHA in post-cryptosin treated membranes indicated a non
      specific type of interaction of cryptosin with mammalian cardiac beta
      adrenoceptors.

PMID- 1980456
TI  - Increased reduced glutathione and glutathione S-transferase activity in chronic
      cephaloridine nephrotoxicity studies in the rat.
AB  - The effect of repeated cephaloridine treatment on renal glutathione and related
      enzymes has been investigated in young adult male and female Sprague-Dawley rats.
      Animals were given intraperitoneally daily doses of either 750 mg/kg for two
      weeks or 500 or 750 mg/kg for three months. Measurement of blood and urinary
      parameters (electrolytes, urea, creatinine) did not reveal any renal function
      impairment and histological examination confirmed the absence of renal damage. By
      contrast, an increase in reduced glutathione (2 to 3-fold) and glutathione S
      transferase activity (1.5 to 2-fold) was observed. These results are consistent
      with the development of an adaptative phenomenon to cephaloridine subchronic
      treatment in the rat, leading to a tolerance to high repeated doses.

PMID- 1980457
TI  - Evaluation of toluene exposure via drinking water on levels of regional brain
      biogenic monoamines and their metabolites in CD-1 mice.
AB  - Toluene, a potentially neurotoxic substance, is found in trace amounts in
      groundwater. Adult male CD-1 mice were continuously fed drinking water ad libitum
      containing 0, 17, 80, and 405 mg/liter toluene. After a 28-day treatment, animals
      were tested for endogenous levels of the biogenic monoamines norepinephrine (NE),
      dopamine (DA), and serotonin (5-HT) and their respective metabolites. 3-methoxy-4
      hydroxymandelic acid (VMA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic
      acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA), in six discrete brain
      regions. The maximum toluene-induced increases of biogenic amines and their
      metabolites generally occurred at a toluene concentration of 80 mg/liter. In the
      hypothalamus, a major NE-containing compartment, the concentrations of NE
      significantly increased by 51, 63, and 34% in groups dosed with 17, 80, and 405
      mg/liter, respectively. Significant increases of NE were also observed in the
      medulla oblongata and midbrain. Concomitantly, concentrations of VMA increased in
      various brain regions. Concentrations of DA were significantly higher in the
      corpus striatum and hypothalamus. Alterations in levels of DA metabolites, DOPAC
      and HVA, were marginal. Toluene significantly increased concentrations of 5-HT in
      all dissected brain regions, except cerebellum, and increased the 5-HIAA levels
      in the hypothalamus, corpus striatum, and cerebral cortex.

PMID- 1980458
TI  - Employment of CEPEX enclosures for monitoring toxicity of Hg and Zn on in situ
      structural and functional characteristics of algal communities of River Ganga in
      Varanasi, India.
AB  - Effects of Hg and Zn on in situ nitrogen fixation, autotrophic index, pigment
      diversity, 14CO2 uptake, and change in algal community structure of Ganges water
      have been studied for the first time using CEPEX chambers in aquatic ecosystem of
      India. A concentration-dependent decrease in in situ nitrogenase activity of
      Ganges water with Hg and Zn has been noticed. No ethylene production was observed
      at 0.8 microgram/ml of Hg. However, an increase in the autotrophic index was
      observed in CEPEX enclosures treated with Hg and Zn. The AI value was maximum at
      0.8 microgram/ml Hg after an incubation of 15 days. An increase in pigment
      diversity also followed the pattern of AI with the test metals used. Inhibition
      of 14CO2 uptake of phytoplankton of Ganges water was maximum at 0.8 microgram/ml
      Hg (79%) followed by Zn (69%). Carbon fixation showed an increase for 1 hr, after
      which no appreciable change was noticed. Maximum inhibition of algal number was
      observed at 0.8 microgram/ml Hg followed by 8.0 micrograms/ml of Zn in the CEPEX
      chamber. Members of Chlorophyceae showed more tolerance than Cyanophyceae and
      Bacillariophyceae. The filamentous forms were more tolerant to Hg and Zn. In
      contrast, unicellular forms were more sensitive to Hg. The test of significance
      (ANOVA) showed that metal-induced variations in pigment diversity, the
      autotrophic index, and the 14CO2 uptake were highly significant (P less than
      0.001).

PMID- 1980459
TI  - [The effect of dopaminergic pharmacological agents on the pancreatic islet
      apparatus in rats].
AB  - Experimental studies were carried out on white male sexual mature healthy rats
      with induced alloxan diabetes, to clarify the role of dopaminergic system in the
      regulation of functions of the insular apparatus of the pancreas. The experiments
      were performed by the following drugs: bromrcripine, levodopa, a combination of
      revodopa plus carbidopa and haloperidol. Parameters of carbohydrate metabolism
      were determined in the course of acute and chronic experiments. The results
      sustained the hypothesis for participation of dopaminergic system in the
      regulation of production and secretion of insulin and respectively in the control
      of carbohydrate metabolism. Independent studies were carried out on white rats
      with alloxan diabetes after combined administration of dopaminergic
      pharmacological drugs and sulphanylureic preparation (SUP)-glybenclimide. The
      mechanisms of interaction after the combined administration of the investigated
      drugs under the conditions of experimental diabetes mellitus were clarified. The
      obtained results supplement data, in support of the hypothesis for the role of
      dopamine as a neuromediator in the regulation of the insular apparatus of the
      pancreas.

PMID- 1980460
TI  - [Liposomal systems--prospective drug forms. II. The creation and characterization
      of liposomal systems for the oral use of narcotic analgesics].
AB  - Liposomal systems were prepared for oral usage of narcotic analgesics morphine
      and phentanyl. The systems were examined for homogeneity in respect to seize size
      and form of liposomal structures by a diffraction-laser method and electron
      microscopy. The liposomal drug forms were studied on biological experiment as the
      change in the body temperature of rats was described. It was established that in
      rats oral usage of liposomal systems with morphine respectively with phentanyl
      caused significantly better effect in comparison with active substances, not
      taken in liposomes.

PMID- 1980461
TI  - Pharmacology of the hypothermic response to 5-HT1A receptor activation in humans.
AB  - The selective 5-HT1A receptor ligand ipsapirone (IPS) caused dose-related
      hypothermia in humans. The response was attenuated by the nonselective 5-HT1/2
      receptor antagonist metergoline and was completely antagonized by the
      nonselective beta-adrenoceptor antagonist pindolol, which interacts
      stereoselectively with the 5-HT1A receptor. The selective beta 1-adrenergic
      antagonist betaxolol had no effect. The findings indicate that IPS-induced
      hypothermia specifically involves activation of (presynaptic) 5-HT1A receptors.
      Therefore, the hypothermic response to IPS may provide a convenient in vivo
      paradigma to assess the function of the presynaptic 5-HT receptor in affective
      disorders and its involvement in the effects of psychotropic drugs.

PMID- 1980462
TI  - ICI 141,292 (epanolol)--pharmacokinetics after single and repeated oral
      administration in the elderly with moderate renal impairment.
AB  - The pharmacokinetics of ICI 141,292 (epanolol) were studies over 3 days after a
      single oral 200 mg dose and then over 24 h after 12 consecutive daily oral 200 mg
      doses in 16 elderly subjects (aged 65 to 94 years) with moderate renal impairment
      (mean creatinine clearance 33.2 ml.min-1). There was wide inter-individual
      variability in peak plasma ICI 141,292 concentrations (Cmax) but no significant
      difference was found between mean Cmax after a single dose (44.3 ng.ml-1) and
      after 12 doses (37.4 ng.ml-1). The mean observed time to peak plasma ICI 141,292
      concentration (tmax) after a single dose (1.61 h) did not differ significantly
      from that after 12 doses (1.75 h). On several occasions an analytically
      significant second peak in ICI 141,292 plasma concentration was observed.
      Following the peak(s), the plasma concentrations declined biphasically and a mean
      terminal phase plasma half-life (t1/2) of 28.3 (range 10.2-84.8) h was calculated
      after a single dose. The inter-individual variability in the area under the
      plasma concentration-time curve to 24 h AUC (0-24) was 54 fold but there was no
      significant difference between AUC (0-24) after a single dose (mean 226.0 ng.h.ml
      1) and AUC (0-24) after 12 consecutive doses of ICI 141,292 (mean 232.4 ng.h.ml
      1). The results show that consecutive daily administration of 12 oral doses of
      ICI 141,292 (200 mg) does not result in significant accumulation of drug in
      elderly subjects with moderate renal impairment.

PMID- 1980463
TI  - Withdrawal of chronic beta-adrenoceptorblockade: effects on haemodynamics, blood
      lipids and haemostatic variables.
AB  - The effect of cessation of chronic beta-adrenoceptorblockade on heart rate, blood
      pressure, blood lipids and selected haemostatic factors have been measured in 22
      patients recovering from myocardial infarction. Clinical examination and blood
      tests were performed before and 12 weeks after withdrawal of beta-adrenoceptor
      blockade, which had lasted for an average of 3 y. No effect was found on blood
      pressure. There was a significant increase in heart rate of 12%. Total
      cholesterol declined by 9%, high density lipoprotein (HDL-cholesterol) increased
      by 12%, and triglycerides decreased by 6%. The triglyceride dependent factors,
      plasminogen activator inhibitor (PAI-1) and factor VII-phospholipid complex, were
      not affected.

PMID- 1980464
TI  - Repeated dose effects of lormetazepam and flurazepam upon driving performance.
AB  - The residual effects of lormetazepam 1 mg and 2 mg in soft gelatine capsules on
      driving performance were assessed and compared to those of flurazepam 30 mg,
      which is also a powerful hypnotic, but possesses a far less favourable
      pharmacokinetic profile with a long-acting sedative metabolite. Driving
      performance was tested 10 to 11 h and 16 to 17 h post administration, after 2
      days on placebo (baseline), and 2, 4 and 7 days of drug treatment (active), and
      after 1 and 3 days following the resumption of placebo (washout). The driving
      test consisted of operating an instrumented motor-vehicle over a 72 km highway
      circuit in light traffic. Flurazepam 30 mg significantly impaired the ability to
      control the lateral position of the vehicle compared to placebo baseline
      measurements. The degree of impairment was substantial in the female subjects and
      was greater in the morning than in the afternoon. Lormetazepam 1 mg showed no
      residual effect on driving performance. Lormetazepam 2 mg impaired driving
      performance to some extent on the following morning, 10 to 11 h post
      administration, but no residual effect was found in the afternoon. All drugs
      improved sleep quality and prolonged sleep duration to more or less the same
      extent.

PMID- 1980465
TI  - Biliary excretion of H2-receptor antagonists.
AB  - The biliary excretion of ranitidine and famotidine has been studied using
      percutaneous biliary drainage in patients with complete extrahepatic biliary
      obstruction due to pancreatic carcinoma. Following 50 mg ranitidine i.v. 0.7 to
      2.6% of the dose was recovered in bile collected over 24 h. At steady state (300
      mg ranitidine/d po) a similar amount (0.3 to 1.0% of daily dose) was excreted by
      this route (n = 3). Following single i.v. (20 mg) and oral (40 mg) doses of
      famotidine (n = 2), even lower percentages (0.1% and 0.4%, respectively) were
      recovered in the 24 h bile. This negligible biliary excretion cannot account for
      the so-called second peak phenomenon observed in some individuals following a
      single dose of an H2-receptor antagonist.

PMID- 1980466
TI  - Influence of okadaic acid on the control of liver mRNA levels.

PMID- 1980468
TI  - pH-induced structural transitions in beta-lactoglobulin.

PMID- 1980467
TI  - Dipeptidyl peptidase IV in human lymphocytes: molecular properties.

PMID- 1980469
TI  - The polymerase chain reaction applied to identification of specific alleles of
      the bovine milk protein genes.

PMID- 1980470
TI  - Reduction in transglutaminase activity associated with tumour metastasis is due
      to the presence of an inactive form of the enzyme.

PMID- 1980471
TI  - Pharmaceutical research in Canada.

PMID- 1980472
TI  - Calcium-induced vasocontractions after alpha-2 adrenergic receptor activation in
      the dog saphenous vein: comparison to calcium-induced contractions after
      potassium-depolarization.
AB  - 1. Calcium mediated contractile effects were evoked in phenoxybenzamine (10(-7)
      M)-pretreated dog saphenous vein (DSV) rings under the continuing presence of
      norepinephrine (3 x 10(-5) M), a condition that selectively activates alpha 2
      (alpha 2)-adrenergic receptors. 2. Calcium-induced contractions in this model
      were dose-dependently inhibited by the alpha 2 antagonists rauwolscine and SKF
      86466, while the calcium channel blockers nifedipine and verapamil produced only
      small non-dose related inhibitions. The receptor antagonists sulpiride,
      buspirone, pyrilamine and atropine showed no inhibitory effect. 3. In contrast,
      rauwolscine and SKF-86466 produced no inhibition of the calcium-evoked
      contractions in potassium-depolarized DSV rings, in which nifedipine and
      verapamil exhibited potent calcium antagonist activity. 4. These data provide
      evidence to support the presence of alpha 2 related receptor-operated calcium
      channels in vascular smooth muscle, which are pharmacologically distinguishable
      from potential-dependent calcium channels.

PMID- 1980473
TI  - The membrane stabilizing and beta 1-adrenoceptor blocking activity of (+)- and (
      )-propranolol on the rat left atria.
AB  - 1. The membrane stabilizing and beta 1-adrenoceptor blocking activities of (+)-
      and (-)-propranolol have been determined using the rat left atria. 2. (+)- And (
      )-propranolol have membrane stabilizing activity. Thus a low concentration of (-)
      propranolol, 10(-8) M, and a higher concentration of (+)-propranolol, 10(-6) M,
      inhibited the responses to electrical stimulation. A high concentration of (+)-
      and (-)-propranolol, 10(-5) M, also inhibited the maximal combined response to
      electrical stimulation and isoprenaline. 3. As competitive beta 1-adrenoceptor
      antagonists, (-)-propranolol was over a 100 times more potent than (+)
      propranolol.

PMID- 1980474
TI  - Calcium-dependent actions of the convulsant barbiturate, CHEB, on transmitter
      release at the rat neuromuscular junction.
AB  - 1. The effect of convulsant barbiturates on spontaneous and evoked acetylcholine
      release was studied at the rat neuromuscular junction in vitro. 2. The convulsant
      barbiturates (+)-5-(1,3-dimethylbutyl)-5-ethyl barbituric acid [(+)-DMBB], 5-(2
      cyclohexylideneethyl)-5-ethyl barbituric acid (CHEB), 5-ethyl-5-(3-methylbut-2'
      enyl) barbituric acid (3M2B) and 5-ethyl-5-(1,3-dimethylbut-1'-enyl) barbituric
      acid (1,3M1B) all produced a concentration-dependent increase in miniature end
      plate potential (MEPP) frequency. 3. With CHEB (100 microM) this increase in MEPP
      frequency was found to be dependent on the [Ca2+]o. CHEB in 0.5 mM [Ca2+]o did
      not alter MEPP amplitude, but in 1.3 and 2.5 mM [Ca2+]o CHEB significantly
      reduced the amplitude. 4. At a [Ca2+]o of 0.5 mM, CHEB produced an increase in
      both EPP amplitude and quantal content, while at 1.3 mM [Ca2+]o CHEB did not
      alter EPP amplitude or quantal content. 5. The plot of log quantal content vs log
      [Ca2+]o showed a parallel shift to the left in the presence of 100 microM CHEB.
      This change occurred without any alteration in the maximum quantal content. This
      suggests that the enhancement of transmitter release may be mediated by an effect
      on calcium fluxes in the pre-junctional nerve terminal.

PMID- 1980475
TI  - Evidence for postsynaptic alpha 1- and alpha 2-adrenoceptors mediating
      catecholamine-induced negative chronotropic ventricular responses in the
      conscious dog.
AB  - 1. Adrenaline (0.25-1 microgram/kg), noradrenaline (0.125-0.5 microgram/kg) and
      dopamine (25-100 micrograms/kg) given in the conscious dog with chronic atrio
      ventricular block after beta-adrenoceptor blockade, increased ventricular cycle
      length (VCL) and mean blood pressure (MBP). 2. Atropine (muscarinic receptor
      blocker) reduced the catecholamine-induced effects on VCL without modifying their
      hypertensive effects. 3. Phenoxybenzamine or phentolamine (alpha-adrenoceptor
      blockers) only decreased the effects of adrenaline on VCL but suppressed those of
      noradrenaline and dopamine. They only reduced the effects of adrenaline and
      noradrenaline on MBP, but reversed that of dopamine. 4. Yohimbine (alpha
      adrenoceptor blocker) suppressed the catecholamine-induced effects on VCL, and
      reduced strongly the hypertensive effects of adrenaline and noradrenaline and
      reversed that of dopamine. 5. Thus, these results show the existence of negative
      chronotropic postsynaptic alpha-adrenoceptors in the ventricles.

PMID- 1980476
TI  - Differential activation of Xenopus homeo box genes by mesoderm-inducing growth
      factors and retinoic acid.
AB  - What is the nature of positional information during embryogenesis? By using
      Xenopus homeo box genes as anteroposterior (A-P) markers, we confirm the findings
      of others that mesoderm-inducing growth factors and retinoic acid (RA) can
      provide positional information along the axis of the body. Xenopus tissue culture
      mesoderm-inducing factor (XTC-MIF) selectively activates an anteriorly expressed
      homeo box gene (XlHbox 1), while basic fibroblast growth factor (bFGF) activates
      selectively a posteriorly expressed homeo box gene (XlHbox 6). RA activates
      expression of the posterior gene XlHbox 6, but not of XlHbox 1. This activation,
      however, requires exposure to growth factors. The data suggest that growth
      factors and RA may cooperate with each other to provide positional information in
      vertebrates.

PMID- 1980477
TI  - Endonucleolytic cleavage of a maternal homeo box mRNA in Xenopus oocytes.
AB  - We have identified a messenger RNA (mRNA) sequence from a Xenopus homeo box
      containing gene that is the target for a sequence-specific endoribonuclease in
      vivo. Synthetic RNA transcribed from an allele of the maternal gene Xlhbox2B is
      efficiently cleaved when injected into Xenopus oocytes. The cleavage sequence
      lies between the protein-coding region and a 600-base 3'-untranslated region.
      Intermediates in degradation are readily observed: Both the 5' and 3' products of
      cleavage are recovered, thus showing that the cleavage activity is an
      endonuclease. When a 90-base region of the Xlhbox2B sequence is inserted into a
      second homeo box RNA that is normally stable, it is sufficient to confer an
      identical cleavage reaction on the hybrid RNA. The cleaved region contains a
      repeated sequence motif and is cut at multiple sites. Inhibition of translation
      does not affect the rate or extent of cleavage, while the coinjection of
      antisense RNA complementary to the 90-base region completely blocks the reaction.
      Because most mRNAs are not found on polysomes during oogenesis, translation
      independent cleavage at such sites may provide a novel post-transcriptional
      mechanism to regulate the amount of mRNA available for embryogenesis.

PMID- 1980478
TI  - The oct-1 homeo domain contacts only part of the octamer sequence and full oct-1
      DNA-binding activity requires the POU-specific domain.
AB  - The ubiquitous octamer-binding protein oct-1 contains a POU domain required for
      DNA binding, which can be subdivided into a POU-specific domain and a POU homeo
      domain. We have overproduced the POU domain and the POU homeo domain in a
      vaccinia expression system, purified both polypeptides to near homogeneity, and
      compared their DNA-binding properties. In contrast to the POU domain, the homeo
      domain protects only part of the octamer sequence in the Ad2 origin against
      breakdown by DNase I or hydroxyl radicals. Analysis of purine contacts by DMS and
      DEPC interference assays shows that the Ad2 octamer can be divided into two
      regions: one that is recognized both by the POU domain and the homeo domain in an
      identical fashion, and one that is only recognized by the POU domain. This
      suggests that the POU-specific domain is responsible for the additional contacts
      located at one side of the octamer. In agreement with this, mutating the first 3
      nucleotides (ATG) of the octamer affected binding by the POU domain but not by
      the homeo domain. The apparent binding affinities to different octamer sites were
      compared. The homeo domain binds 600-fold less efficiently to the canonical
      octamer sequence (ATGCAAAT) than the POU domain. The difference is only sevenfold
      for the Ad2 octamer, whereas both Kd values are almost identical for the HSV ICP4
      TAATGARAT motif. Both the POU and homeo domains recognize target sequences for
      mammalian homeo box proteins. We conclude that the octamer can act as a bipartite
      recognition sequence for oct-1 and that the POU-specific domain contributes to
      the binding affinity, as well as to the specificity, by providing additional
      contacts.

PMID- 1980479
TI  - Multidrug resistance: focus in hematology.
AB  - The appearance of chemoresistance is the most relevant limitation of
      chemotherapy. It has been shown that multidrug resistance (MDR) is frequently
      related to the expression of a membrane glycoprotein (P-170). This protein is
      able to bind ATP and leads to decreased accumulation of structurally unrelated
      antineoplastic drugs extensively used in the management of hematological
      patients. The availability of monoclonal antibodies and probes allowed extensive
      studies both "in vitro" and "in vivo" of the protein structure and of its
      mechanism of action. The P 170 activity may be antagonized by drugs able to
      compete with chemotherapic agents for the binding or by calcium antagonists that
      inhibit the expulsion activity of the protein. P 170 has been found in variable
      percentages of several hematological malignancies such as leukemia,
      myelodysplastic syndromes, myeloma and lymphoma. The reported data seem to
      indicate that the patients carrying P 170-positive neoplastic cells should be
      treated with drugs that are not bound by the protein. However, the possibility of
      inhibiting the protein function and the recent reports suggesting the use of P
      170 as a target for immunotoxins could be the basis for new therapeutic
      protocols.

PMID- 1980480
TI  - HTLV-I positive adult T-cell leukaemia-lymphoma: report of a typical case from
      Italy.
AB  - A case of acute adult T-cell leukemia-lymphoma (ATLL) was observed in northeast
      Italy, presenting with fever, lymphadenomegaly, splenomegaly, hypercalcemia and
      renal failure. Leukaemic cells were morphologically typical, expressed a T-cell
      CD4+ phenotype, did not display any helper functions, and grew in vitro under
      supply of exogenous interleukin-2. Antibodies to human T-cell lymphotropic virus
      (HTLV-I) were found in the serum, and the virus was isolated from leukaemic
      cells. The family members who could be tested were seronegative. The patient had
      never travelled outside Italy, had never received blood transfusions and did not
      belong to any known categories at risk of viral disease transmission. Present
      knowledge of the epidemiology of HTLV-I infection warns that other cases of HTLV
      I induced disease are expected to occur outside already recognised endemic areas.
      This case suggests that untraceable, presumably short-term exposures can also
      account for HTLV-I transmission.

PMID- 1980482
TI  - Use of psychostimulants for the elderly.
AB  - As the number of people over age 65 continues to grow, a clear understanding of
      the usefulness and limitations of psychostimulants in treating elderly persons
      becomes more important. The authors review the limited literature and discuss the
      use of psychostimulants for treating "senility," including their effects on
      cognition, amotivational syndromes, and depression. They conclude that early
      studies of "senile" patients suffered from a lack of clear diagnostic standards
      and did not address the issue of whether measurements of the target symptoms
      being assessed were reliable or valid. The authors suggest that future studies
      more clearly define age groups, diagnostic criteria, and scales to measure the
      effects of psychostimulants.

PMID- 1980481
TI  - Angiocentric lymphoma: a case report.
AB  - A group of rare lymphoproliferative disorders, now called
      angioimmunoproliferative lesions, are histologically characterized by mononuclear
      cells surrounding and infiltrating vessel walls. This process results in
      angiodestruction and originates necrosis. Angiocentric lymphoma, a neoplasia
      generally deriving from the T cell lineage, is the most aggressive form of these
      entities characterized by prevalent extranodal involvement. A case of primary
      angiocentric lymphoma with lymph-nodel and systemic presentation and rapidly
      fatal outcome is described.

PMID- 1980483
TI  - Medication compliance and substance abuse among schizophrenic patients.
AB  - The relationship between use of alcohol and street drugs and compliance with
      prescribed medication before admission to an acute psychiatric inpatient setting
      was studied in 42 schizophrenic patients, more than half of whom had a history of
      alcohol abuse or dependence. Most patients, even those without a history of
      alcohol abuse, admitted to drinking alcohol in the month before admission.
      Alcohol abusers drank significantly more often and drank significantly greater
      quantities than nonabusers. The majority of patients were noncompliant with
      prescribed medication before admission, and most of these patients specifically
      reported being noncompliant when drinking alcoholic beverages.

PMID- 1980484
TI  - The AIMS examination.

PMID- 1980485
TI  - Manic depressive illness not linked to factor IX region in an independent series
      of pedigrees.
AB  - We studied seven informative kindreds segregating for manic depressive illness
      (MDI), consistent with X-chromosome transmission of the trait (families do not
      show affective disease in both a father and a son), using markers mapped to the
      region of Xq27-Xq28. The lod scores were consistently below -2 in the region
      extending from about 10 cM centromeric from the Factor IX locus (F9) to the
      colorblindness region. This study does not replicate previous reports of linkage
      of MDI to Factor IX (Xq27) and colorblindness region (Xq28) chromosomal markers
      in other kindreds.

PMID- 1980486
TI  - Structure of the human methylmalonyl-CoA mutase (MUT) locus.
AB  - The MUT locus encoding the enzyme methylmalonyl-CoA mutase is defective in mut
      forms of methylmalonic acidemia. This locus has been mapped to chromosome 6p12
      21.1. We report cloning and characterization of this locus which comprises 13
      exons spanning greater than 35 kb of the genome. The MUT locus exhibits consensus
      sequences for transcription, splicing, and polyadenylation. The putative promoter
      region was localized in a CG island 5' to exon I and was shown to direct
      expression of a beta-galactosidase reporter gene in cultured cells. Of interest
      is the observation that the first intron occurs within the 5' untranslated
      region, and no introns separate the mitochondrial targeting sequences and the
      mature apoenzyme. An informative HindIII polymorphism was localized within the
      coding sequence and can be assayed using the polymerase chain reaction. These
      studies describe the structure of the MUTlocus and provide a foundation for
      characterization of mutations in mut methylmalonic acidemia.

PMID- 1980487
TI  - Direct haplotyping by double digestion of PCR-amplified creatine kinase (CKMM):
      application to myotonic dystrophy diagnosis.

PMID- 1980488
TI  - Dissociation of signal transduction via Thy-1 and CD3 antigens in murine T cells.
AB  - To understand the proliferation/differentiation of immature thymocytes which have
      not express T cell antigen receptor (TCR), we studied whether Thy-1 has signal
      transducing capacity. Thy-1+ CD3-TCR- cells including thymocytes from BALB/c
      embryos and SCID mice and nude mouse splenic cells did not show proliferative
      responses in the culture with anti-Thy-1 (G7) plus phorbol myristate acetate
      (PMA), whereas Thy-1+ CD3+ cells from normal thymus or spleen did show a response
      to them. Since Thy-1-mediated activation is suggested to require co-expression of
      the CD3-TCR complex, we compared the T cell proliferative response in mature T
      cells stimulated with anti-Thy-1 (G7) and anti-CD3-epsilon (2C11). Under the
      presence of PMA or IL-2, accessory cell-depleted splenic T cells were cultured
      with G7 or 2C11. PMA augmented the proliferative response of splenic T cells
      cultured with G7 much more than that with 2C11. IL-2, however, showed reciprocal
      effect on the proliferation of G7 and 2C11-treated splenic T cells. These data
      suggest that signals triggered via Thy-1 and CD3-epsilon may provide a distinct
      intracellular pathway for T cell activation.

PMID- 1980490
TI  - Cyclic hexapeptides related to somatostatin. Conformational analysis employing 1H
      NMR and molecular dynamics.
AB  - We report the conformational analysis of a series of cyclic hexapeptides related
      to the hormone somatostatin utilizing 1H NMR spectroscopy and NOE restrained
      molecular dynamics. The conformational preferences and results from biological
      analysis of these analogs (previous paper) allow for refinement of the current
      understanding of the structure-activity relationship of somatostatin. For most of
      the molecules examined, a beta II' turn about the D-tryptophan-lysine residues,
      postulated to be required for biological activity, was present. From the NOE
      restrained molecular dynamics, it can be seen that the turn structure is
      important for the maintenance of the proper orientation of the side chains of the
      adjacent phenylalanine, tryptophan and lysine. The biologically active analogs
      have the side chains of lysine and D-tryptophan extended away from the 18
      membered ring in close proximity to each other for a significant portion of the
      dynamic simulations. Although other conformations are accessible and monitored
      during the simulations, we believe this is important for biological recognition.
      The absence of the beta II' turn at the D-tryptophan-lysine disrupts this side
      chain array producing inactive molecules. The role of the bridging region, the
      Phe-Pro dipeptide, is to stabilize the beta II' turn and help maintain the proper
      orientation of the biologically important side chains.

PMID- 1980489
TI  - Cyclic hexapeptides related to somatostatin. Synthesis and biological testing.
AB  - As a continuation of our program to study the structure-function relationship of
      the peptide hormone somatostatin, we report the synthesis and biological
      potencies of a series of cyclic hexapeptide analogs related to somatostatin. The
      parent peptide of this series was designed by Veber and coworkers, c[-Pro6-Phe7-D
      Trp8-Lys9-Thr10-Phe11-], and has been reported to be superactive in the
      inhibition of the release of growth hormone. (The superscript numbers refer to
      the positions of residues in native somatostatin). The series of analogs has been
      designed to examine the role of the so-called bridging region, Phe11-Pro6, which
      has been postulated to be important in maintaining the proper conformation of the
      biologically active tetrapeptide, Phe-D-Trp-Lys-Thr. We have incorporated
      peptidomimetics and the retro-inverso modification into the bridging region of
      the molecule, with the aim of affecting the conformational preferences found in
      the parent peptide. Results from the biological assay--in vitro inhibition of
      growth hormone--and the conformational analysis (adjoining paper) of our analogs
      will provide insight into the relationship between structure and biological
      activity of somatostatin.

PMID- 1980491
TI  - Quantitative structure-activity relationships for sea anemone polypeptide toxins.
AB  - Sea anemone polypeptides vary considerably in their affinities for sodium
      channels occurring in different excitable cells. The amino acid sequence
      variation in a set of six sea anemone type I polypeptide toxins (46-49 residues
      long), was parameterized using descriptor scales z1, z2, and z3, derived from a
      large number of amino acid physicochemical properties. The pharmacological
      properties of the toxins were represented by the results from four bioassays on
      crab, mouse, and rat brain and from rat heart. By means of the descriptor scales
      and the multivariate data analytical method PLS (partial least squares
      projections to latent structures), it was possible to develop quantitative
      structure-activity relationships (QSAR). Using the QSARs derived from the set of
      six polypeptide toxins the pharmacological properties of two homologous sea
      anemone polypeptide toxins were predicted. Thus it is shown that QSARs may be
      formulated for relatively long bioactive polypeptides. The QSARs indicate that 11
      different amino acid positions may be of importance, but that positions no. 5,
      21, 28, 34, 37, and 40 were of main importance in modeling the relative
      toxicities of the six polypeptides.

PMID- 1980492
TI  - Ghana: ICN/WHO Workshop spreads word on AIDS.

PMID- 1980493
TI  - Increase in the level of P-glycoprotein mRNA expression in multidrug-resistant
      K562 cell lines treated with sodium butyrate is not accompanied with erythroid
      differentiation.
AB  - We examined the effect of hemin, sodium butyrate and mitomycin C on levels of P
      glycoprotein mRNA in human myelogenous K562 cells by northern blot analysis.
      After treatment with sodium butyrate a dose-dependent increase of P-glycoprotein
      mRNA expression was observed in the adriamycin-resistant K562 and vincristine
      resistant K562 lines. With 10 mM sodium butyrate, the level of P-glycoprotein
      mRNA reached 20 times that of control adriamycin-resistant K562 and with 30 mM
      sodium butyrate, it exceeded 5 times that of control vincristine-resistant K562.
      In contrast, hemin and mitomycin C had almost no effect on P-glycoprotein mRNA.
      In this experiment, since expression of P-glycoprotein mRNA was not necessarily
      accompanied with induction of erythroid differentiation, the increased amount of
      P-glycoprotein mRNA is unlikely to be a result of differentiation.

PMID- 1980495
TI  - Gene expression of D-amino acid oxidase in rabbit kidney.
AB  - Although D-amino acid oxidase (DAO) [EC 1.4.3.3] activity in rabbit kidney
      extract was undetectable, protein immunoreactive toward rabbit anti-pig kidney
      DAO antiserum and RNAs that hybridized with fragments of human and pig DAO cDNAs
      were detected distinctly in the rabbit kidney. A cDNA clone, RD22, was isolated
      from the rabbit kidney cDNA library by hybridization with a fragment of human DAO
      cDNA. Analysis of the nucleotide sequence revealed a 2,018 nucleotide sequence
      encoding a protein consisted of 347 amino acids. The number of amino acid
      residues was identical with those of human and pig DAOs, and the amino acid
      sequence showed 80 and 83% identity with pig and human DAOs, respectively. RNAs
      that hybridized with RD22 DNA fragment also existed in rabbit kidney, and their
      sizes were the same as those of the RNAs detected with the human and pig DAO cDNA
      fragments. RD22-derived protein was hardly synthesized by an in vitro expression
      system. However, a cDNA fragment lacking most of the 5'-untranslated region and
      its mutants containing base changes around the initiation codon did direct
      protein synthesis. Moreover, the protein derived from the partial cDNA fragment
      containing a large part of the coding region sequence showed immunoreactivity
      toward anti-pig DAO antiserum. The results suggest that one of the causes of the
      very poor synthesis of DAO protein in rabbit kidney is translational suppression
      in the synthetic process.

PMID- 1980494
TI  - In vitro bone formation on coral granules.
AB  - We investigated the ability of fetal rat bone cells isolated after collagenase
      digestion to differentiate in vitro and to produce a mineralized matrix on coral
      granules. Scanning electron microscopy examination of the surface of the seeded
      coral granules revealed that cells attached, spread, and proliferated on the
      material surface. Bone nodule formation was studied in this in vitro system by
      direct examination under an inverted phase contrast microscope. The initial event
      observed was the appearance of cells with phosphatase alkaline activity arranged
      in several layers and forming a three-dimensional organization around the coral
      particles. By Day 7, nodule formation began and a refringent material appeared
      and extended to the background cells during the following days. By Day 15, some
      coral granules were embedded in a mineralized matrix. Histologic results
      demonstrated the formation of a mineralized tissue with the appearance of woven
      bone.

PMID- 1980497
TI  - Assay of gamma-glutamylcysteine synthetase and glutathione synthetase in
      erythrocytes by high-performance liquid chromatography with fluorimetric
      detection.

PMID- 1980496
TI  - A centrosomal antigen localized on intermediate filaments and mitotic spindle
      poles.
AB  - A monoclonal antibody (CTR2611) raised against centrosomes isolated from human
      lymphocytes (KE37) stains the pericentriolar material and intermediate filaments
      in the same cells. In MDCK cells, where most of the microtubules do not originate
      from the pericentriolar region during interphase, the antigen is distributed
      along intermediate filaments. At the onset of mitosis, a large fraction of the
      CTR2611 antigen associates with the minus-end domain of the microtubules of the
      mitotic spindle but not with the pericentriolar region itself. Treatment of
      mitotic MDCK cells with taxol leads to the assembly of many microtubule asters in
      the cytoplasm at the expense of the mitotic spindle. The CTR2611 antigen is
      present in the center of each of these asters. Similar asters can also be
      produced in vitro by adding taxol to concentrated Xenopus egg mitotic cytoplasm.
      Again, the antigen is found close to the center of the asters. These results
      suggest that CTR2611 antigen is associated with a material involved in
      microtubule nucleation or microtubule minus-end stabilization. The monoclonal
      antibody recognizes a 74 x 10(3) Mr polypeptide and other polypeptides at 120 x
      10(3) Mr and 170 x 10(3) Mr. The 74 x 10(3) Mr polypeptide is found in all
      species examined so far, suggesting that it contains a highly conserved epitope.

PMID- 1980499
TI  - Cyclosporine in dermatology. Proceedings of a symposium. Orlando, Florida,
      January 27-28, 1990.

PMID- 1980498
TI  - New natural products in cancer chemotherapy.
AB  - Four new and clinically relevant antineoplastic natural products are reviewed.
      Taxol is derived from the bark of the western yew. It promotes the formation of
      microtubule bundles which deform the cytoskeleton and interfere with mitosis.
      Although phase II efficacy testing is incomplete, taxol is effective in the
      treatment of patients with ovarian carcinoma and has some activity in patients
      with non-small cell lung cancer and melanoma. It remains untested against several
      other neoplasms. The chief toxicities of taxol are myelosuppression, mucositis,
      anaphylactoid reactions, and peripheral neuropathy. Homoharringtonine is the most
      active and abundant of the cephalotaxine esters derived from the genus
      Cephalotaxus. This agent appears to act at the ribosome to inhibit protein
      synthesis and has clinical activity in patients with acute myelogenous leukemia.
      The dose limiting toxicities of homoharringtonine are hypotension and
      myelosuppression. SKF 104864 and CPT-11 are derivatives of camptothecin which are
      still in early clinical trials. They are cytotoxic in vitro, acting through an
      interaction with topoisomerase I to induce DNA fragmentation. The spectra of
      activity and toxicity of SKF 104864 and CPT-11 are still undefined. All four of
      these new natural products offer possibilities for clinical activity for patients
      with a variety of malignancies.

PMID- 1980500
TI  - Proliferating cell nuclear antigen/cyclin in cultured human keratinocytes.
AB  - Expression of proliferating cell nuclear antigen (PCNA)/cyclin in cultured human
      keratinocytes was studied using an antibody from an SLE patient as the reagent.
      By indirect immunofluorescence staining, SV40-transformed human keratinocytes
      expressed PCNA/cyclin in 40-45% of the cells as a nulcear granular fluorescence.
      After synchronization of these cells, their nuclear distribution pattern during
      the S phase was sequential and showed a clear correlation with DNA synthesis.
      Primary cultured keratinocytes grown in high Ca+ medium expressed PCNA/cyclin in
      10-15% of the cells with a similar staining pattern. These positively stained
      cells were confined to the basal and immediate suprabasal layers of the
      stratified culture sheet. The keratinocytes disaggregated by trypsin were
      separated according to cell size through a screen of Nitex monofilament cloth.
      The cells smaller than 15 microns in diameter synthesized abundant PCNA/cyclin,
      while the larger cells expressed very low levels. These results indicate that the
      expression of PCNA/cyclin correlates with DNA synthesis in cultured
      keratinocytes, but is not associated with their differentiation process.

PMID- 1980501
TI  - State of the art in typing: Klebsiella spp.

PMID- 1980502
TI  - The use of the wound scoring method 'ASEPSIS' in postoperative wound
      surveillance.
AB  - For the purposes of wound surveillance programmes and clinical trials, a wound
      scoring method, ASEPSIS, makes assessment of wound sepsis more objective and
      reproducible by allotting points both for the appearance of the wound in the
      first week and for the clinical consequences of infection. ASEPSIS was compared
      with other definitions of wound infection in 1029 surgical patients and its
      suitability for surveillance and detection of risk factors were examined.
      Satisfactory healing was recorded in 867 patients, disturbance of healing in 74
      and minor, moderate and severe wound infection in 41, 24 and 23 patients
      respectively. An ASEPSIS score over 20 points was more sensitive and as specific
      as the presence of pus as an indicator of changes in management resulting from
      infection. Multiple regression analysis of ASEPSIS scores indicated that
      operation type, ward, degree of contamination, age, body mass index, and
      preoperative stay in hospital were significant risk factors. In matching 52
      infected patients with uninfected controls, any wound score over 10 points was
      associated with a significant delay in discharge from hospital (median 3 days, P
      less than 0.0005).

PMID- 1980503
TI  - Effect of three plastic catheters on survival and growth of Pseudomonas
      aeruginosa.
AB  - The effect of polyvinylchloride (PVC), polyurethane (PU) and siliconized latex
      (SL) catheters on the survival and growth of six non-mucoid and three mucoid
      strains of Pseudomonas aeruginosa was evaluated. Pseudomonas aeruginosa (1 x
      10(8)) was incubated in PBS alone (control) or with 30 1-cm length segments of
      each catheter and the number of viable microorganisms was determined after 8 h,
      1, 2, 5, 7 and 10 days. The presence of PVC catheters significantly favoured the
      survival and growth of non-mucoid strains in comparison to the control (P less
      than 0.05 at 5 days, P less than 0.01 at 7 days and thereafter); a similar result
      was observed with SL catheters (P less than 0.05 at 2 days, P less than 0.01 at 5
      days and thereafter). No differences were observed with PU catheters. The number
      of mucoid microorganisms decreased with time in all controls and suspensions
      containing segments of catheter, but non-mucoid revertants appeared and quickly
      increased in the presence of PVC and SL (but not PU) catheters. Eluates of PBS
      previously containing PVC or SL segments induced a 100- to 500-fold increase in
      the growth of a non-mucoid strain in comparison with PBS alone. It is concluded
      that some plastic catheters can release substance(s) that favour the viability of
      P. aeruginosa.

PMID- 1980504
TI  - Epidemiological surveillance of Acinetobacter species.
AB  - Two hundred and sixty Acinetobacter isolates were recovered from 237 patients
      over a 2-year period; 156 isolates from 135 spinal cord injuries unit (SCIU)
      patients and 104 isolates from 102 patients in all the other hospital units. In
      SCIU patients, 133 isolates were recovered from the urine, 21 from wounds and
      aspirates, one from sputum and one from blood culture. In non-SCIU patients, 12
      isolates were recovered from urine, 43 from wounds and aspirates, 48 from sputum
      and one from blood culture. Sixty-nine percent of isolates from SCIU patients
      showed resistance to gentamicin compared to 3% from non-SCIU patients. Gentamicin
      resistant Acinetobacter anitratus was recovered from many environmental sites in
      the SCIU wards and from the hands of seven of 94 SCIU staff members tested.
      Serial rectal swabs were obtained from 79 newly-diagnosed SCIU patients. Ninety
      two percent of those patients followed for up to 5 months acquired gentamicin
      resistant Acinetobacter anitratus in their intestinal tract. API 2ONE profiles
      and antibiograms suggested that two distinct gentamicin-resistant strains of A.
      anitratus had become endemic in the SCIU and that nosocomial transmission was a
      frequent occurrence.

PMID- 1980505
TI  - An in-use evaluation of decontamination of polypropylene versus steel bedpans.
AB  - A prospective cross-over study in three different wards has demonstrated the lack
      of effect of two disinfectants compared with a detergent when added to the
      washing cycle of automatic bedpan washers that employ hot water centrally
      supplied at 60 degrees C. An unexpected and potentially important finding was
      that polypropylene pans were much more effectively cleaned and decontaminated
      than their stainless steel counterparts. The role, if any, of bedpans in the
      epidemiology of nosocomial infections remains a mystery. The continued absence of
      information clearly incriminating these ubiquitous devices in the transmission of
      potential pathogens, or of genes encoding antibacterial drug resistance, raises
      questions as to whether extensive efforts to achieve a high degree of
      decontamination of bedpans are necessary at all.

PMID- 1980506
TI  - Economic effects of nosocomial infections in cardiac surgery.
AB  - A study of 60 infected patients and matched controls showed that nosocomial
      infection in cardiac surgery cost each patient an additional 2207 yuan (pounds
      290). The cost of multisite infection was much higher. Infected patients were in
      hospital for a mean of 14 extra days.

PMID- 1980507
TI  - Pseudomonas aeruginosa orbital cellulitis in four neutropenic patients.
AB  - Four neutropenic patients on a haematology ward developed orbital cellulitis due
      to different strains of Pseudomonas aeruginosa over a 7-month period.
      Investigation of patients and the ward environment revealed two P. aeruginosa
      isolates indistinguishable from the infecting strains in a plastic washing bowl
      and a sink in a single cubicle respectively. These items were unlikely to have
      been the sources of the infecting strains but were a potential cross infection
      hazard. Treatment of orbital cellulitis is discussed briefly.

PMID- 1980508
TI  - Revised guidelines for the control of epidemic methicillin-resistant
      Staphylococcus aureus. Report of a combined working party of the Hospital
      Infection Society and British Society for Antimicrobial Chemotherapy.

PMID- 1980509
TI  - Cryptosporidium muris is particularly hazardous for people with suppressed immune
      systems from drugs or diseases, e.g. AIDS.

PMID- 1980510
TI  - Human infections with strains of Agrobacterium.

PMID- 1980511
TI  - Preventable hazard of blood spillages at venepuncture.

PMID- 1980512
TI  - Endotoxins on surgical gloves.

PMID- 1980513
TI  - Seven FMRFamide-related and two SCP-related cardioactive peptides from Helix.
AB  - Pulmonate snails have a more complex array of cardioexcitatory peptides than
      other molluscs, and Helix has a more complex array than most other pulmonates.
      Since a full characterisation of the cardioexcitatory peptides is necessary for
      an understanding of physiology, we sought to identify the members of two families
      of such peptides - the small cardioactive peptides (SCPs) and the FMRFamide
      related peptides (FaRPs) - from Helix aspersa. We characterised the peaks of
      immunoreactivity from HPLC both by their elution times and by their molecular
      weights as determined by fast atom bombardment mass spectrometry (FABms). These
      two criteria, used in parallel, facilitated our identification of several known
      peptides: MNYLAFPRMamide, identical to SCPB of Aplysia; two tetrapeptide FaRPs,
      FRMRamide and FLRFamide; and three hepatapeptide FaRPs, NDPFLRFamide,
      SDPFLRFamide and pQDPFLRFamide. Of these peptides, only FMRFamide and
      pQDPFLRFamide have previously been reported from Helix. We also discovered an
      additional SCP and two novel FaRPs and sequenced them. The SCP is Ser-Gly-Tyr-Leu
      Ala-Phe-Pro-Arg-Met-amide (SGYLAFPRMamide), and the heptapeptide FaRPs are Asn
      Asp-Pro-Tyr-Leu-Arg-Phe-amide (NDPYLRFamide) and Ser-Glu-Pro-Tyr-Leu-Arg-Phe
      amide (SEPYLRFamide). When these nine peptides were tested on isolated Helix
      ventricles, the SCPs were the most potent cardioexcitors, the heptapeptide FaRPs
      were next, and the tetrapeptides had the least activity.

PMID- 1980514
TI  - Initiation of swimming activity in the medicinal leech by glutamate, quisqualate
      and kainate.

PMID- 1980515
TI  - Proceedings of the 10th International Congress of the International Society for
      the Study of Vulvar Disease, Washington, D.C., October 1989.

PMID- 1980516
TI  - Exclusion of autosomal dominant polycystic kidney disease type II (ADPKD2) from
      160 cM of chromosome 1.
AB  - Autosomal dominant polycystic kidney disease is a heritable disorder and recent
      studies have shown genetic heterogeneity, with some, but not all, families
      showing linkage with markers on chromosome 16p. Members of a large ADPKD family,
      unlinked to chromosome 16, have been typed for 12 marker loci located on both
      arms of chromosome 1. Multipoint analysis excluded ADPKD2 from the region between
      D1S81 (pTHH33) and D1S67 (pHHH106) on the long arm and between Rh and PGM1 on the
      short arm. This excludes the disease locus from about 61% of chromosome 1.

PMID- 1980517
TI  - [Adrenergic mechanisms in pathophysiology and treatment of chronic circulatory
      failure].

PMID- 1980518
TI  - An assessment of the validity of densitometric measures of striatal tyrosine
      hydroxylase-positive fibers: relationship to apomorphine-induced rotations in 6
      hydroxydopamine lesioned rats.
AB  - The power of immunohistochemical staining as a tool for the study of the
      neurochemical anatomy of the brain would be greatly enhanced if quantitative
      measures of staining were to be developed. We have here assessed the reliability
      and validity of two population measures of extent of fiber innervation: percent
      area occupied by staining, and average optical density (AOD) of staining. We have
      evaluated these measures for tyrosine hydroxylase-positive staining of the
      striatum in relation to apomorphine-induced rotational behavior in 6
      hydroxydopamine lesioned rats. We have found that inter-operator reliability for
      the area measure is high (r = 0.98). Apomorphine-induced rotations were observed
      when the area measured was reduced to 2% or less of the control side, and when
      the density measure was reduced to 15% or less. These results are similar to
      those obtained previously for biochemical assay of TH activity, which showed
      rotations at reductions to 10% or less. We conclude that these density measures
      provide valid relative indices of extent of fiber innervation on the same
      section. The AOD measure appears to be more sensitive at lower levels of
      innervation.

PMID- 1980519
TI  - The role of type 1 pili in the pathogenesis of Escherichia coli infections: a
      short review and some new ideas.

PMID- 1980520
TI  - A strategy for the pharmacotherapy of personality disorders.
AB  - Current research reveals that biological factors play an important role in
      shaping normal and disordered personality features. Judicious use of medications
      can facilitate the treatment of individuals with personality disorders.

PMID- 1980521
TI  - [Immunohistochemical study of epidermal growth factor receptor and c-erbB.2
      oncogene product in bile duct carcinoma: preliminary report].

PMID- 1980522
TI  - A new family of polymorphic genes in Saccharomyces cerevisiae: alpha
      galactosidase genes MEL1-MEL7.
AB  - Using genetic hybridization analysis we identified seven polymorphic genes for
      the fermentation of melibiose in different Mel+ strains of Saccharomyces
      cerevisiae. Four laboratory strains (1453-3A, 303-49, N2, C.B.11) contained only
      the MEL1 gene and a wild strain (VKM Y-1830) had only the MEL2 gene. Another wild
      strain (CBS 4411) contained five genes: MEL3, MEL4, MEL5, MEL6 and MEL7. MEL3
      MEL7 were isolated and identified by backcrosses with Mel- parents (X2180-1A,
      S288C). A cloned MEL1 gene was used as a probe to investigate the physical
      structure and chromosomal location of the MEL gene family and to check the
      segregation of MEL genes from CBS 4411 in six complete tetrads. Restriction and
      Southern hybridization analyses showed that all seven genes are physically very
      similar. By electrokaryotyping we found that all seven genes are located on
      different chromosomes: MEL1 on chromosome II as shown previously by Voll-rath et
      al. (1988), MEL2 on VII, MEL3 on XVI, MEL4 on XI, MEL5 on IV. MEL6 on XIII, and
      MEL7 on VI. Molecular analysis of the segregation of MEL genes from strain CBS
      4411 gave results identical to those from the genetic analyses. The homology in
      the physical structure of this MEL gene family suggests that the MEL loci have
      evolved by transposition of an ancestral gene to specific locations within the
      genome.

PMID- 1980523
TI  - Localization by restriction fragment length polymorphism mapping in potato of a
      major dominant gene conferring resistance to the potato cyst nematode Globodera
      rostochiensis.
AB  - A major dominant locus conferring resistance against several pathotypes of the
      root cyst nematode Globodera rostochiensis was mapped on the linkage map of
      potato using restriction fragment length polymorphism (RFLP) markers. The
      assessment of resistance versus susceptibility of the plants in the experimental
      population considered was based on an in vivo (pot) and an in vitro (petri dish)
      test. By linkage to nine RFLP markers the resistance locus Gro1 was assigned to
      the potato linkage group IX which is homologous to the tomato linkage group 7.
      Deviations from the additivity of recombination frequencies between Gro1 and its
      neighbouring markers in the pot test led to the detection of a few phenotypic
      misclassifications of small plants with poor root systems that limited the
      observation of cysts on susceptible roots. Pooled data from both tests provided
      better estimates of recombination frequencies in the linkage interval defined by
      the markers flanking the resistance locus.

PMID- 1980524
TI  - Molecular genetic analysis of chalcone synthase in Lycopersicon esculentum and an
      anthocyanin-deficient mutant.
AB  - Twelve loci have previously been identified in tomato (Lycopersicon esculentum)
      that control the intensity and distribution of anthocyanin pigmentation; these
      are useful genetic markers because they encode phenotypes that are readily
      visualized in the hypocotyls of emerging seedlings. In order to obtain molecular
      probes for tomato anthocyanin biosynthesis genes, we isolated two cDNAs which
      encode chalcone synthase (CHS), one of the key enzymes in anthocyanin
      biosynthesis, from a tomato hypocotyl cDNA library. By comparing their nucleic
      acid sequences, we determined that the two CHS cDNAs have an overall similarity
      of 76% at the nucleotide level and 88% at the amino acid level. We identified
      hybridization conditions that would distinguish the two clones and by Northern
      analysis showed that 1.5 kb mRNA species corresponding to each cDNA were
      expressed in cotyledons, hypocotyls and leaves of wild-type seedlings.
      Hybridization of the cDNAs at low stringency to genomic blots indicated that in
      tomato, CHS genes comprise a family of at least three individual members. The two
      genes that encode the CHS cDNAs were then placed onto the tomato genetic map at
      unique loci by restriction fragment length polymorphism mapping. We also assayed
      the activity of CHS and another enzyme in the anthocyanin pathway, flavone 3
      hydroxylase, in hypocotyl extracts of wild-type tomato and a number of
      anthocyanin-deficient mutants. Five mutants had reduced CHS activity when
      compared to the wild-type controls. Of these, three were also reduce in flavone 3
      hydroxylase activity, suggesting a regulatory role for these loci. The other two
      mutants were preferentially reduced in CHS activity, suggesting a more specific
      role for these loci in CHS expression.

PMID- 1980525
TI  - Temporal specificity in the action of stimuli during the formation of associative
      ultrastructural reorganizations in neurons of the cerebral cortex.
AB  - A morphometric investigation of various components of the synapses of neurons of
      the sensorimotor region of the cerebral cortex of rats with different variants of
      combined and uncombined repeated microiontophoretic application of glutamate and
      acetylcholine has been carried out. A substantial dependence of the character and
      expressivity of the reorganizations of the thickness of the postsynaptic density
      (PSD), of the width of the synaptic cleft, and the length of the active zone of
      the synapses, on the temporal relationships in the action of mediators has been
      identified: significant changes in the thickness of the PSD appeared only with
      the combined applications of the stimuli (neuromediators); the maximum thickening
      of the PSD was induced by the combined action of glutamate and acetylcholine with
      a 3-second delay in the latter. A hypothesis is presented according to which the
      temporal specificity in the integration of associable signals arriving at neurons
      is determined by the kinetics of the various interacting biochemical regulator
      mechanisms.

PMID- 1980527
TI  - Competitive inhibition of NMDA-mediated responses by guanine nucleotides in brain
      synaptic membranes treated with Triton X-100.
AB  - The effect of guanine nucleotides on physiological responses mediated by the N
      methyl-D-aspartate (NMDA)-sensitive subclass of brain excitatory amino acid
      receptors was examined by using NMDA-sensitive [3H]L-glutamic acid (Glu) binding
      as well as [3H](+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imi ne
      (MK-801) binding in rat brain synaptic membranes treated with a low concentration
      of Triton X-100. The NMDA-sensitive [3H]Glu binding was significantly inhibited
      by the addition of some guanine nucleotides such as GTP, GDP, 5'
      guanylylimidodiphosphate and guanosine 5'-O-(3-thiotriphosphate), but not by
      other nucleotides or nucleosides such as guanosine, cyclic GMP, adenosine, AMP,
      ADP, ATP, CTP, ITP and UTP. Inclusion of GTP not only attenuated the ability of
      NMDA to displace [3H]Glu binding in a concentration-dependent manner, but also
      lowered the affinity of the binding sites for [3H]Glu without altering their
      densities. The inhibitory potency of an antagonist highly selective to the NMDA
      receptors (+/-)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonate on [3H]Glu
      binding also deteriorated with GTP at concentrations above 10 microM. Addition of
      Glu induced a concentration-dependent potentiation of [3H]MK-801 binding through
      an activation of the NMDA-sensitive receptors, and the potency of Glu to
      potentiate the binding was markedly reduced by the afore-mentioned positive
      guanine nucleotides in a competitive manner. In contrast, GTP at 0.1 mM non
      competitively weakened the stimulatory property of glycine to additionally
      enhance the binding found in the presence of Glu alone. These results suggest
      that some guanine nucleotides may have a relatively high affinity for NMDA
      recognition sites within the NMDA receptor complex in the brain.

PMID- 1980526
TI  - The role of cGMP in the extinction of the reactions of identified neurons of the
      edible snail in response to acetylcholine.
AB  - The possible role of cGMP in the regulation of the extinction of the reactions of
      the RPa4, RPa3, and LPa3 neurons of the edible snail in response to acetylcholine
      (ACh), applied rhythmically to the soma of the neuron by means of
      microiontophoresis, has been investigated. It was demonstrated that activators of
      guanylate cyclase which increased the level of cGMP in the cell, namely, sodium
      nitroprusside and sodium azide (5.10(-4)-10(-3) mole/liter), when applied
      intracellularly, intensify the extinction of inward transmembrane current and of
      depolarization of the membrane in response to ACh. The hypothesis of the
      participation of cGMP-dependent phosphorylation of membrane proteins in the
      regulation of the rate of development, depth, and duration of short-lived
      plasticity of the cholinoreceptors of the neuron is proposed.

PMID- 1980528
TI  - Excitatory amino acid transmitters and their receptors in neural circuits of the
      cerebral neocortex.
AB  - In 1954, L-glutamate (Glu) and L-aspartate (Asp) were first suggested as being
      excitatory synaptic transmitters in the cerebral cortex. Since then, evidence has
      mounted steadily in favor of the view that Glu and Asp are major excitatory
      transmitters in the neocortex. Many of the experimental studies which reported
      how Glu/Asp came to satisfy the criteria for transmitters in the neocortex are
      reviewed here, according to the methods employed. Since the question of which
      particular synaptic sites in cortical neural circuits Glu/Asp operate as
      excitatory transmitters has not previously been reviewed, particular attention is
      given to efferent, afferent and intrinsic neural circuits of the visual and
      somatosensory cortices, where circuitry is relatively clearly delineated. Recent
      studies using chemical assays of released amino acids, high-affinity uptake
      mechanisms of Glu/Asp from nerve terminals, the direct micro-iontophoretic
      administration of Glu/Asp antagonists, and immunocytochemical techniques have
      demonstrated that almost all corticofugal efferent projections employ Glu/Asp as
      excitatory synaptic transmitters. Evidence indicating that thalamocortical
      afferent projections, including geniculocortical projections and some intrinsic
      connections are glutamatergic, is also reviewed. Thus, the results highlighted
      here indicate that the main framework of neocortical circuitry is operated by
      Glu/Asp. Pharmacological studies indicate that synaptic receptors for Glu/Asp can
      be classified into a few subtypes, including N-methyl-D-aspartate (NMDA) and
      quisqualate/kainate (non-NMDA) types. Some evidence indicating the sites of
      operation of NMDA and non-NMDA receptors in neocortical circuitry is reviewed,
      and the distinct, functional significance of these two types of Glu/Asp receptors
      in information processing in the neocortex is proposed.

PMID- 1980529
TI  - Muscarinic control of gallbladder dynamics. A study using 99Tcm-HIDA and
      cholinergic agonists and antagonists.
AB  - We studied 12 normal subjects who underwent four 99Tcm-HIDA examinations. Imaging
      was performed with 111 MBq at 1 image/min for 60 min, and was registered on a
      computer on a 64 x 64 word matrix. Normalized and background corrected time
      activity curves on the gallbladder were obtained from which total and cumulative
      10 min interval emptying was calculated. During the first examination (control),
      10 min after the beginning of acquisition, 1 ml saline solution was injected
      subcutaneously. The second examination was performed injecting 5 mg bethanechol
      subcutaneously instead of saline solution. During the third and fourth
      examinations 10 mg pirenzepine and 0.15 mg/10 kg atropine were injected i.v.
      respectively, 5 min before bethanechol injection. Wilcoxon's test was used to
      compare the first and second studies and the latter with the third and fourth
      studies. The median value of gallbladder emptying at 60 min was 2% with saline
      solution injection and 27.5% with bethanechol. This difference was significant
      from minute 30 onwards. Atropine administration inhibited gallbladder emptying
      completely in all cases, with significant differences (P less than 0.01) in
      relation to bethanechol values following the first 30 min of the examination.
      Gallbladder emptying was observed in the study with pirenzepine, but was
      significantly inferior to the bethanechol values after the first 30 min.

PMID- 1980530
TI  - Rethinking quality--nationally and regionally.

PMID- 1980531
TI  - [Reconstructive surgery of malunited joint fractures of the foot].
AB  - Innovative diagnostic methods such as the CT scan, MRI and 3rd-dimensional models
      of the foot and free-flap surgery to improve the soft tissues in the foot have
      all introduced new dimensions in reconstructive foot surgery. Of the foot bones
      only intra-articular fractures of the astragalus should be corrected because of
      its key position and the involvement of three joints. In double and triple
      arthrodesis, the axes and lengths of the medial and lateral columns should be
      corrected to prevent arthritis at the higher or lower joint level. Pan-talar
      arthrodesis can be worse than a well-done amputation below the knee. Cannulated
      6.5 cancellous screws in double and triple arthrodesis and 3.5 corticalis screws
      in Lisfranc fusions allow stable fixation and function early after treatment.

PMID- 1980532
TI  - Enzymes of transmitter and energy metabolism in cat middle ear muscles.
AB  - Activities of the enzymes choline acetyltransferase (ChAT) and
      acetylcholinesterase (AChE), which metabolize the neuromuscular transmitter
      acetylcholine, and malate and lactate dehydrogenase (MDH and LDH), enzymes of
      oxidative and glycolytic energy metabolism, respectively, were measured in the
      middle ear muscles of the cat. For comparison, the same enzyme activities were
      measured in extraocular muscle tissue and in three hindlimb muscles rich in
      either slow oxidative (soleus), fast glycolytic (white part of vastus lateralis),
      or fast oxidative glycolytic (plantaris) muscle fibers. ChAT and AChE activities
      were much higher in middle ear muscles than in hindlimb muscles, consistent with
      a denser neuromuscular innervation, as in extraocular muscles. By contrast, MDH
      and LDH activities were remarkably low in the middle ear muscles, lower than in
      any of the hindlimb muscles or the extraocular muscles. Denervation of the
      stapedius muscle by peripheral transection of the facial nerve resulted in
      decreases in all four enzyme activities without associated changes in the tensor
      tympani. Surgical ablation of the peripheral facial nerve supply to the stapedius
      muscle appears to be a feasible option for producing its denervation. The results
      suggest some rather specialized chemical characteristics for the middle ear
      muscles.

PMID- 1980533
TI  - Argon laser irradiation of the otolithic organ.
AB  - An argon laser was used to irradiate the otolithic organs of guinea pigs and
      cynomolgus monkeys. After stapedectomy, the argon laser (1.5 W x 0.5 sec/shot)
      irradiated the utricle or saccule without touching the sensory organs. The stapes
      was replaced over the oval window after irradiation. The animals used for acute
      observation were killed immediately for morphologic studies; those used for long
      term observation were kept alive for 2, 4, or 10 weeks. Acute observation
      revealed that sensory and supporting cells were elevated from the basement
      membrane only in the irradiated area. No rupture of the membranous labyrinth was
      observed. Long-term observation revealed that the otolith of the macula utriculi
      had disappeared in 2-week specimens. The entire macula utricili had disappeared
      in 10-week specimens. No morphologic changes were observed in cochlea,
      semicircular canals, or membranous labyrinth. The saccule showed similar changes.

PMID- 1980534
TI  - Free amino acid analysis of guinea pig perilymph: a possible clinical assay for
      the PLF enigma?
AB  - Controversy prevails regarding the accuracy of the clinical diagnosis of
      perilymphatic fistula (PLF). The diagnosis of PLF has been based on the
      subjective evaluation of vestibular function tests and the intraoperative
      macroscopic visualization of "clear fluid" from the oval/round windows at the
      time of exploratory tympanotomy. However, the subjective visual characterization
      of PLF varies among observing surgeons. Furthermore, perilymph can be
      "contaminated" with serum, blood, cerebrospinal fluid (CSF), and local
      anesthesia. This article presents a scientific biochemical microassay for the
      free amino acid profile of perilymph. Microaliquots of uncontaminated perilymph
      were sampled from the bilateral round windows (scala tympani) of 20 guinea pigs
      and analyzed for 19 free amino acid concentrations (FAAC) by high-performance
      liquid chromatography (HPLC). These samples were compared with the FAAC of guinea
      pig serum samples. Perfect predictor value ranges were nonoverlapping for 12 of
      19 free amino acids in perilymph vs. plasma. Amino acid microassay of middle ear
      fluid for verification of "true" perilymph vs. nonperilymph fluids by the
      identification of nonoverlapping FAA markers may allow scientific verification of
      the existence of PLF in "suspected" patients.

PMID- 1980535
TI  - Suppression of a hind limb flexion withdrawal reflex by microinjection of
      glutamate or morphine into the periaqueductal gray in the rat.
AB  - Microinjection into the midbrain periaqueductal gray (PAG) or lateral reticular
      formation (LRF) of the neuronal excitant glutamate produces analgesia, and
      suppresses the responses of a fraction of spinal dorsal horn neurons to noxious
      heat applied to ventral hind paw skin. Microinjection of morphine into the PAG
      also produces analgesia, but has been reported to frequently facilitate, as well
      as to suppress or have no effect, on nociceptive spinal neurons. In anesthetized
      rats, we tested whether (a) glutamate microinjections into PAG or LRF, and (b)
      morphine microinjections into PAG, affected the isometric force of hind limb
      withdrawal elicited by the same noxious heat stimuli on the hind paw as used in
      single-unit studies of dorsal horn neurons. Glutamate (0.5 M; 0.1-0.5 microliter)
      microinjected at 9/12 PAG and 8/10 LRF sites suppressed the reflex, and had no
      effect or facilitated the reflex from the remaining sites. Morphine (5 micrograms
      in 0.5 microliter) microinjected at each of 10 PAG sites suppressed the reflex in
      a naloxone-reversible manner. Suppression usually began shortly after morphine,
      peaked at 20-40 min, and lasted greater than 60 min. The integrated flexion
      reflex thus appears to be more susceptible to chemical midbrain stimulation under
      these experimental conditions, compared to previous studies of single dorsal horn
      neurons.

PMID- 1980536
TI  - Pharmacokinetic and pharmacodynamic profiles of opioid analgesics: a sameness
      amongst equals?

PMID- 1980537
TI  - Profiles of opioid analgesia in humans after intravenous bolus administration:
      alfentanil, fentanyl and morphine compared on experimental pain.
AB  - This report examines the relationship of plasma drug concentration to analgesic
      effect following bolus doses of alfentanil, fentanyl and morphine and assesses
      individual differences in analgesic response among volunteers. We predicted that
      the 3 opioids would yield disparate analgesic profiles because their
      physicochemical and pharmacokinetic characteristics differ. Ten healthy
      volunteers received intravenous bolus doses of either alfentanil, fentanyl,
      morphine or normal saline on different days. We stimulated their teeth
      electrically and measured brain evoked potential (EP) and pain report (PR)
      repeatedly over 2 h to assess analgesic effect. Concurrently, we drew 18 blood
      samples to assess opioid plasma concentrations during the test period. The
      relationship between opioid plasma concentration and analgesic effect was well
      defined for alfentanil but ambiguous for morphine. Fentanyl exhibited a marked
      hysteresis. We observed noteworthy individual differences in analgesic response
      with all 3 drugs but these differences were greatest for morphine and least for
      alfentanil. Inter- and intrasubject variability in analgesic response across
      drugs is related to the physicochemical properties of the drugs tested.

PMID- 1980539
TI  - On the IIIrd Latin American Cystic Fibrosis Congress (III Congreso
      Latinoamericano de Fibrosis Quistica and III Simposio Pan-americano de
      Neumonologia Pediatrica)

PMID- 1980538
TI  - Effect of altering smooth muscle tone on maximal expiratory flows in patients
      with tracheomalacia.
AB  - We obtained maximal partial expiratory flow-volume (PEFV) curves using the rapid
      compression technique in three infants with intrathoracic tracheomalacia. Maximum
      flows were quantitated at functional residual capacity (VmaxFRC). Studies were
      performed at baseline, after inhalation of methacholine (MCh) and after
      inhalation of albuterol. At baseline, all three patients had significantly lower
      than normal VmaxFRC values, and two patients displayed expiratory flow limitation
      during tidal breathing. VmaxFRC improved significantly after MCh administration,
      but fell back toward or below baseline after albuterol. Additionally, the ratio
      of forced to tidal flows at mid-tidal volume (Vmid(forced/tidal), a reflection of
      expiratory flow reserve, increased after MCh administration and decreased after
      albuterol. Two patients also received oral bethanechol: 2.9 mg/M2, q 8 hr for 10
      days, after which PEFV curves were repeated. Both Vmax FRC and Vmid(forced/tidal)
      were increased over baseline after bethanechol administration, but decreased
      after albuterol. These results suggest that in patients with abnormally
      collapsible tracheae, stimulation of tracheal smooth muscle can improve airway
      stability, thereby increasing forced expiratory flows. Additionally, relaxation
      of airway smooth muscle by bronchodilators can have the opposite effect and
      exacerbate obstruction.

PMID- 1980540
TI  - Toxoplasma gondii infection during pregnancy: T lymphocyte subpopulations in
      mothers and fetuses.
AB  - Prenatal diagnosis of fetal toxoplasmosis is possible with the use of fetal blood
      sampling, amniocentesis and ultrasound examination. The purpose of this study was
      to describe T lymphocyte subsets (CD3, CD4 and CD8) in mothers and their fetuses
      when Toxoplasma gondii infection occurred during pregnancy. Maternal and fetal
      blood samples were obtained in 86 cases and 9 fetuses showed T. gondii infection.
      Control groups consisted of 30 healthy nonpregnant women and 30 pregnant women.
      Pregnant women with T. gondii infection showed an increase in the suppressor
      (CD8) T subpopulation and a significant depression in the total helper (CD4) T
      cells. These alterations were more important in mothers whose fetus was infected.
      We showed the progressive maturation of the fetal immune system with a regular
      increase of all T lymphocyte subsets. Marked alterations were observed in the 9
      infected fetuses (depression of CD4 population and lower CD4/CD8 ratio). In the
      future these differences might be used as a new marker of the severity of fetal
      lesions and become a useful diagnostic tool.

PMID- 1980541
TI  - Increments in plasma homovanillic acid concentrations after neuroleptic
      discontinuation are associated with worsening of schizophrenic symptoms.
AB  - 1. Thirty-two male schizophrenic patients participated in this study. 2. Plasma
      concentrations of the dopamine metabolite, homovanillic acid (pHVA) were assessed
      once on neuroleptic medication and twice a week for a maximum of six weeks after
      its discontinuation. 3. Psychiatric symptomatology was assessed once on
      neuroleptic medication and once a week for a maximum of six weeks after its
      discontinuation, using the brief psychiatric rating scale (BPRS). 4. pHVA and
      total BPRS score increased significantly after discontinuation of neuroleptic as
      compared to baseline. 5. The magnitude of pHVA and BPRS increments after
      discontinuation of neuroleptic correlated significantly. 6. Results of this study
      suggest that worsening of schizophrenic symptoms after discontinuation of
      neuroleptic treatment is associated with increased pHVA concentrations.

PMID- 1980542
TI  - Subjective neuroleptic response and treatment outcome under open and double-blind
      conditions--a preliminary report.
AB  - 1. A patient's early subjective response to a neuroleptic was recorded in 17
      schizophrenic patients following a fixed dose of neuroleptic under both open and
      double-blind placebo-controlled conditions. 2. High correlations were found
      between a patient's subjective response at 2.5, 24 and 48 hours after the initial
      dose, suggesting that the timing of the initial subjective response rating is not
      critical. 3. The relationship between the psychiatric improvement and subjective
      response was not significant under double-blind conditions (r = 0.004), while the
      relationship under the open condition showed a trend towards significance
      comparable to earlier reports (r = 0.32). 4. The findings question the usefulness
      of applying early subjective response to a neuroleptic to predict clinical
      improvement.

PMID- 1980543
TI  - Aspartic acid release from cerebral cortical slices of E1 mice with high seizure
      susceptibility.
AB  - Unlike their parent strain ddY mice, inbred mutant E1 mice are highly susceptible
      to convulsive seizures upon tossing stimulation. The uptake and release of
      [3H]aspartate by cerebral neocortical slices were investigated in non-stimulated
      E1 mice [E1(-)], in stimulated E1 mice [E1(+)] and also in ddY mice using a
      superfusion system. The uptake and release of aspartate in E1(-) were lower than
      in E1(+) or ddY. However, the aspartate level in the cerebral cortex of E1(-) was
      higher compared to that of E1(+) or ddY. Addition of aspartate into the medium
      resulted to a decreased potassium-stimulated aspartate release in ddY, an
      increased in E1(-), and no change in E1(+). The results suggest that abnormal
      state of aspartate release and/or uptake in cerebral cortex of E1 mice may
      contribute to their increased susceptibility of seizures.

PMID- 1980544
TI  - Intestinal motility disorder induced by peroxides: possible role of lipid
      peroxidation.
AB  - The effect of oxidative stress on the rat small intestine was investigated by
      pretreatment of isolated segments from the jejunum with hydrogen peroxide or
      cumene hydroperoxide. Both peroxides induced responses in the small intestine,
      viz. a contraction followed by a slow relaxation. The contraction could be
      blocked by the cyclooxygenase inhibitor indomethacin and the phospholipase A2
      inhibitor quinacrine, suggesting a role for prostaglandins in the response.
      Pretreatment of intestinal segments with the peroxides diminished the muscarinic
      cholinergic response to methacholine. The lipoxygenase inhibitor
      nordihydroguaiaretic acid (NDGA) and the antioxidant butylated hydroxytoluene
      (BHT) both protected against the damage induced by cumene hydroperoxide, but did
      not influence the effect of hydrogen peroxide on the muscarinic response. In
      contrast to hydrogen peroxide, cumene hydroperoxide induced lipid peroxidation in
      intestinal membranes, which could also be blocked by NDGA or BHT. We conclude
      that cumene hydroperoxide alters the muscarinic response in the rat jejunum by
      the induction of lipid peroxidation, whereas the damage by hydrogen peroxide is
      probably induced intracellularly.

PMID- 1980545
TI  - Current concepts in emesis control. Sixth International Conference on Cancer
      Nursing. August 15, 1990, Amsterdam. Proceedings.

PMID- 1980546
TI  - [Drug-induced arterial hypertension].

PMID- 1980547
TI  - [Parkinsonian syndrome. Etiology, diagnosis, treatment].

PMID- 1980548
TI  - Highlights of Gastroenterology in The Netherlands, 1990. Proceedings of a
      symposium. 19-22 April 1990, Crete, Greece.

PMID- 1980549
TI  - Potential hazards of long-term acid suppression.
AB  - Neuroendocrine cell (carcinoid) tumours have been reported in the acid-secreting
      part of the stomach of rodents after long-term administration of a range of
      potent chemically diverse antisecretory agents. Although evidence shows a link
      between the sequence of acid suppression, hypergastrinaemia, and neuroendocrine
      cell hyperplasia, other factors are also thought to be involved in neoplastic
      transformation. Prolonged hypochlorhydria or achlorhydria resulting in bacterial
      colonization of the stomach may allow the generation of carcinogenic substances.
      Other as yet unidentified trophic factors may be involved in tumour formation. In
      view of the potential risks associated with these agents, there must be concern
      about the possible consequences in man of marked suppression of acid. It seems
      wise to limit the use of these more potent agents to situations in which
      conventional therapy has failed and to short-term treatment.

PMID- 1980550
TI  - [Humoral factors in the modulation of sustained discharges of polymodal
      nociceptors].
AB  - By using a model of sustained discharges of polymodal nociceptors (PMN) due to
      injection of a compound algogenic substance into the skin in anesthetized rats,
      it was found that stimulation of the sciatic nerve inhibited or facilitated at
      first and then inhibited the PMN sustained discharges markedly. In a
      crossperfused preparation, stimulation of the sciatic nerve of donor rat caused
      the similar effects on sustained discharges of PMN of the recipient rat.
      Injection of the animal serum after stimulation of the sciatic nerve affected PMN
      activity obviously. The inhibitory course of most units could not be reversed by
      naloxone. In the animal tolerance to morphine, the effects of stimulation of the
      sciatic nerve could still be obtained. Preadministration of reserpine almost
      completely abolished the facilitatory effect. The results indicate that sustained
      activity of PMN could be modulated by some humoral factors due to somatic
      afferents. The inhibitory substances in the humoral factor seem to be both opioid
      and nonopioid in nature. The facilitatory substance seem to be a catecholamine.

PMID- 1980551
TI  - [Inhibitory effect of secretin on gastric motility in isolated vascular perfused
      rat stomach].
AB  - Effect of secretin on gastric motility was studied on the preparation of isolated
      vascular perfused rat stomach. The results showed: (1) Secretin markedly
      inhibited spontaneous as well as pentagastrin stimulated antral motility. (2)
      Antisecretin serum completely abolished the inhibitory effect of secretin on
      antral motility. (3) Antisomatostatin serum and indomethacin blocked the
      inhibitory effect on antral motility induced by secretin. The results indicated
      that the inhibitory effect of secretin might be produced through direct action of
      secretin on secretin receptors and mediated partially by the local somatostatin
      and prostaglandin in gastric antrum.

PMID- 1980552
TI  - A nucleotide substitution in a Bg1 II site is responsible for the RFLP
      discrimination between DPw4 and DPa.
AB  - In a previous work we showed that the two functionally different specificities
      DPw4 and DPa could only be differentiated by RFLP analysis using two mutually
      exclusive fragments (respectively, Bg1 II 5.29 kb for DPw4 and 7.24 kb for DPa).
      The DP Workshop synthetic analysis localized these fragments in the DPA2
      pseudogene region. Our results demonstrate, however, that they are located
      between the A1 and B1 genes; the Bg1 II restriction site responsible for the 5.29
      kb fragment was localized between the first and second exon of the DPB1 gene and
      inside the 7.24 kb fragment. A single mutation point inside this restriction site
      is responsible for the absence of the 5.29 kb fragment, changing the specificity
      attributed by RFLP typing.

PMID- 1980553
TI  - Mitochondria, molecular chaperone proteins and the in vivo assembly of
      microtubules.
AB  - Two proteins, P1 and P2, which are specifically altered in mammalian cell mutants
      resistant to antimitotic drugs, have been identified as the homologs of two
      members of the class of proteins known as molecular chaperones. P1 is localized
      in mitochondria and P2-related proteins are involved in the translocation of
      proteins to mitochondria. To account for these and a number of other
      observations, a new model for in vivo microtubule assembly is proposed.

PMID- 1980554
TI  - Immunocytochemistry of thyroid C-cell complexes in dogs.
AB  - Ten thyroid C-cell complexes from five male and five female Beagle dogs, 1 to 2
      years old, were studied using single and double immunocytochemical staining with
      the peroxidase-antiperoxidase technique. The antigens tested included
      thyroglobulin, calcitonin, calcitonin gene-related peptide, somatostatin, neuron
      specific enolase, and neurotensin. All C-cell complexes contained four cell types
      in various proportions: 1) follicular cells staining for thyroglobulin; 2) C
      cells staining for calcitonin, calcitonin gene-related peptide, and neuron
      specific enolase; 3) stellate cells and cuboidal cells in follicle-like
      structures staining positively for somatostatin; and 4) undifferentiated cells
      staining negatively for all antigens. No positive immunoreactivity for
      neurotensin was detected. These findings support the hypothesis that thyroid C
      cell complexes are ultimobranchial remnants that can give rise to thyroid
      follicles and C-cells.

PMID- 1980555
TI  - In situ hybridization for the detection of human parvovirus B19 nucleic acid
      sequences in paraffin-embedded specimens.
AB  - Parvovirus infection of pregnant women leading to a transplacentar infection of
      the fetus may result in hydrops fetalis, and ultimately in intrauterine death of
      the fetus. In situ hybridization with a biotinylated as well as with a 35S
      labeled probe for human parvovirus B19 was performed on formalin-fixed paraffin
      embedded (FFPE) tissue from a fetus suffering from non-immunologic hydrops
      fetalis. Histology was suggestive of viral infection probably with human
      parvovirus. Parvovirus DNA could be detected and precisely localized mainly in
      the nuclei of erythroid precursors cells within fetal blood vessels of all organs
      examined. There was no detection of B19 nucleic acid in parenchymal cells of the
      placenta or the fetal organs, nor within maternal blood cells. These findings are
      in agreement with the well-known properties of animal parvoviruses to replicate
      exclusively in proliferating cells. Taking into consideration the problems in
      diagnosing human parvovirus infection by light microscopy, we conclude that in
      situ hybridization with an appropriate non-radioactive probe is a valuable, rapid
      and safe complementary detection method for the diagnosis and study of human
      parvovirus infections. The 35S-labeled probe is more sensitive than the
      biotinylated probe, but has the disadvantages of lower resolution of the signal,
      longer duration of the assay, the hazard of radioactivity and the shorter shelf
      life of the probe.

PMID- 1980556
TI  - Lymphocytes from hepatic inflammatory infiltrate kill rat hepatocytes in primary
      culture. Comparison with peripheral blood lymphocytes.
AB  - In the last few years it has become possible in the liver to isolate lymphocytes
      from inflammatory infiltrates and to culture them in vitro. Most of the
      lymphocyte clones obtained are CD 8+ cytotoxic cells, but interactions between
      these lymphocytes and hepatocytes in primary culture have not been analysed
      previously. In this study, cloned human T lymphocytes from liver biopsies and
      from the peripheral blood of patients with chronic hepatitis B or primary biliary
      cirrhosis, after phenotypical and functional characterization into CD 8+ or CD 4+
      cytotoxic lymphocytes, were activated in an antigen-independent fashion by adding
      either anti CD 3 or anti CD 2/R-3 monoclonal antibodies to the cell suspension.
      The activated cells were then coincubated with rat hepatocytes in primary
      culture. The killing capacity of the activated lymphocytes was monitored by light
      and electron microscopy and by measurement of lactic dehydrogenase (LDH)-release
      into the culture medium. It was found that cytotoxic CD 8+, but not CD 4+ helper
      lymphocytes very effectively killed hepatocytes. The killing effect was dependent
      on the time of cocultivation and on effector-target (E/T) ratio. Total breakdown
      of the hepatocyte monolayer was achieved after 10-20 h coculture and at an E/T
      ratio of 10 to 1. As LDH-release in the culture medium reached about 80% of the
      total LDH-content, most of the hepatocytes were lysed by activated lymphocytes.
      Cytotoxic activity of clones obtained from different biopsies was comparable with
      that of clones from peripheral blood. Hepatocytes in primary culture seem to be
      very sensitive to the killing capacity of activated cytotoxic lymphocytes.

PMID- 1980557
TI  - Uniform response of c-raf expression to differentiation induction and inhibition
      of proliferation in a rat rhabdomyosarcoma cell line.
AB  - The clonal rat rhabdomyosarcoma cell line BA-HAN-1C is composed of proliferating
      mononuclear cells, some of which spontaneously fuse to terminally differentiated
      myotube-like giant cells. Both the induction of differentiation by retinoic acid
      (RA) and by sodium butyrate (NaBut), as well as the inhibition of proliferation
      by fetal calf serum (FCS)-depleted medium uniformly resulted in the same effects.
      There was a significant (p less than 0.001) inhibition of proliferation and
      induction of cellular differentiation, as evidenced by a significant (p less than
      0.05) increase in creatine kinase activity. Furthermore, after exposure to RA
      supplemented or FCS-depleted medium, a significant (p less than 0.001) increase
      in the number of myotube-like giant cells was observed. These effects were
      preceded by a uniform enhancement of c-raf mRNA expression, which became evident
      6 h after exposure to RA, NaBut and FCS-depleted media. C-raf mRNA expression
      persisted at an elevated level throughout the observation period of 5 days after
      exposure to RA or NaBut, whereas the increased expression of c-raf mRNA observed
      after FCS-depletion declined near to the basal level after only 24 h.
      Furthermore, a transient c-fos mRNA expression was observed 15 and 30 min after
      exposure to RA-supplemented and FCS-depleted medium but not after exposure to
      NaBut. The present results suggest a possible role of c-raf in the regulation of
      differentiation and proliferation of this cell line. Since all our experiments
      with RA, NaBut and FCS-depletion resulted in an early peak of c-raf mRNA
      expression, it is suggested that this early peak may be sufficient to trigger
      events crucial for differentiation and proliferation of BA-HAN-1C tumor cells.

PMID- 1980558
TI  - Collagenase of hepatocytes and sinusoidal liver cells in the reversibility of
      experimental cirrhosis of the liver.
AB  - In order to explore the cellular source(s) and the behaviour of the
      collagenolytic activity previously described in rat liver homogenates, in the
      reversibility of experimental cirrhosis of the liver, enriched suspensions of
      hepatocytes and of sinusoidal liver cells were obtained by a procedure which
      employs low EDTA concentrations and no bacterial collagenase. Cell suspensions
      were prepared from three different groups of animals: 1) normal controls, 2) rats
      with CCl4-induced cirrhosis of the liver, and 3) rats with swine serum-induced
      cirrhosis of the liver. Animals were sacrificed in each group upon completion of
      treatment and also after 3, 6 and 12 months. In each liver wet weight and
      collagen concentration were determined, and collagenolytic activity of both
      enriched cell suspensions was measured separately. In addition, histological
      studies of liver tissue and ultrastructural examination of cell suspensions were
      performed by standard procedures. Enriched suspensions of both normal hepatocytes
      and sinusoidal liver cells display Ca2(+)-dependent collagenolytic activities.
      Both cell suspensions obtained from each of the two types of cirrhotic livers
      show normal or slightly increased average levels of collagenase activity at the
      time of treatment discontinuation, when average liver collagen content ranges
      from 6 to 10-fold over normal, suggesting that the normal collagenase/collagen
      ratio is disturbed and that collagenolytic activity is deeply decreased in
      relation to the actual liver collagen load.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1980559
TI  - Selenium complexes in the anterior pituitary of rats exposed to L
      selenomethionine.
AB  - Selenium precipitates were demonstrated histochemically by silver amplification
      at light and electron microscopic levels in the anterior pituitary of rats
      exposed to L-selenomethionine (SeMeth). By electron microscopy (EM), the silver
      amplified selenium complexes were identified in somatotrophs, corticotrophs and
      gonadotrophs. Precipitates were observed mainly in the secretory granules and to
      a lesser extent in the lysosomes. The staining intensity increased with
      increasing amounts of SeMeth. Following a single injection of 3.7 mg Se/kg a
      substantial increase in staining was observed during the first 48 h after
      injection and precipitates could still be observed in the anterior pituitary
      after 2 weeks. During a long-term study where the rats were exposed to selenium
      contained in the drinking water (3.0 mg Se/l drinking water for 1, 2 or 4 weeks)
      an increasing amount of precipitates were observed during the first 2 weeks
      followed by a small decrease in staining intensity. Organic selenium, or rather a
      metabolite, is suggested to form bands with endogenous metal, primarily zinc, as
      has been suggested in the brain and anterior pituitary after exposure to sodium
      selenite.

PMID- 1980560
TI  - Immunophenotype of thymoma-associated lymphoid cell component of T-cell type. A
      new analytic procedure in keeping with structural heterogeneities.
AB  - The phenotype of the lymphoid cell component of 35 thymomas was investigated by
      analyzing cryostat sections and lymphocyte suspensions. The morphology in each
      case was determined by examining multiple tissue samples from different parts of
      the tumor. Structural heterogeneity was shown in 14 thymomas, and a homogeneous
      morphology of cortical or medullary or mixed types in the others. To assess
      whether this heterogeneity was correlated with differences in the lymphoid
      phenotype, we analyzed both lymphocyte suspensions and frozen sections from the
      same samples. Phenotypical differences in the suspensions of each thymoma in the
      heterogeneous group were noted and similar differences were also observed in the
      cryostat sections. Phenotypical abnormalities were found in some thymomas. They
      consisted of the simultaneous expression of cortical and medullary markers, which
      was most marked in the heterogenous mixed-type thymomas invading the lung.
      Furthermore, the global phenotype was tested on a pool of lymphocyte suspensions
      in all thymomas. This procedure distinguished cortical, medullary and
      intermediate cortico-medullary immunophenotype models which closely correlated
      with the tumor histology. It was concluded that, due to the frequent structural
      and immunological heterogeneity of thymomas, correct assessment of their lymphoid
      component requires a two-step analysis. This comprises: 1) individual suspensions
      from samples taken from different areas of the same thymoma, and 2) a pool of
      these suspensions. The first step will reveal the different immunological
      characteristics. In the second, the lymphocyte phenotype, which may vary widely
      throughout the tumor, will be represented in its totality. These findings may be
      of great help in predicting clinical patterns, especially possible malignant
      evolution.

PMID- 1980561
TI  - Immunohistochemical demonstration of collagenase and tissue inhibitor of
      metalloproteinases (TIMP) in synovial lining cells of rheumatoid synovium.
AB  - Degradation of fibrillar collagens is a central process in joint destruction in
      rheumatoid arthritis. Collagenase responsible for the collagenolysis has been
      immunolocalized on the extracellular matrix components at the cartilage/pannus
      junction in the rheumatoid joint, but very little is known about cellular source
      of the proteinase. In this paper monospecific antibodies against collagenase and
      tissue inhibitor of metalloproteinases (TIMP) were applied to rheumatoid and
      normal synovium to identify cells synthesizing and secreting the enzyme and its
      inhibitor. By treating the specimens with the monovalent ionophore, monensin,
      both collagenase and TIMP could be immunolocalized in hyperplastic synovial
      lining cells in rheumatoid synovium, but not in the cells of normal synovium.
      Dual immunolocalization studies demonstrated that the majority of the lining
      cells (approximately 64%) produce both collagenase and TIMP, while approximately
      3% of the cells were positive only for collagenase, and 11% only for TIMP.
      Neither collagenase nor TIMP was immunolocalized on the extracellular matrix
      components in the synovia examined. These data suggest that synovial lining cells
      in rheumatoid arthritis secrete both collagenase and TIMP into the joint cavity.
      The role of collagenase in joint destruction in rheumatoid arthritis is discussed
      with reference to the regulation of the activity by TIMP.

PMID- 1980562
TI  - Methodological approaches to immunohistochemical demonstration of beta
      hexosaminidase in human placental and renal tissue with monoclonal antibodies.
AB  - The lysosomal enzyme, beta-hexosaminidase (Hex), was studied in full-term human
      placentas and in renal tissue using monoclonal antibodies raised against Hex
      purified from human placentas. The immunohistochemical reaction for Hex was
      pronounced in trophoblastic cells and macrophages of the basal plate and the
      smooth chorion, but was faint or negative in the amnion as well as in the
      syncytiotrophoblast and Hofbauer cells of the chorionic villi. The maternal
      decidual cells of the basal plate were negative. Biochemical enzyme analysis
      showed the highest activity in basal plate cells (containing trophoblast,
      decidual cells, macrophages and neutrophils) and a low activity in the chorionic
      villi. Placental tissue was less positive with monoclonal antibodies specific for
      Hex A, compared with antibodies reacting with both Hex A and Hex B. Epithelial
      cells of the renal proximal tubules were positive to the same degree with
      antibodies recognizing both Hex A and Hex B as well as those recognizing only Hex
      A.

PMID- 1980563
TI  - Establishment of an epithelioid malignant schwannoma cell line (YST-1).
AB  - A novel cell line, YST-1, was established from an epithelioid malignant
      schwannoma (EMS) that occurred in the upper arm of an 8-year-old girl. YST-1
      cells were polygonal and stellate in shape, contained abundant free ribosomes,
      mitochondria, lysosomes and rough-surfaced endoplasmic reticulum, and grew stably
      with a population doubling time of 40 h. Immunohistochemically, vimentin, S100
      protein and S100 protein beta subunit were positive in the cytoplasm. The xeno
      transplanted tumor in nude mice was composed of cells with an epithelioid
      arrangement similar to the original tumor. The borders of the tumor cells were
      connected intimately without desmosomal junctions, and there were abundant
      organelles in the cytoplasm. YST-1 cells were considered to be of value for
      studying the nature and histogenesis of EMS.

PMID- 1980564
TI  - [Tuberculous lupus].
AB  - A 39-year-old patient, veterinary feldsher, suffering for 3 years from
      tuberculosis luposa with multiple foci of involvement, is described. The process
      was complicated by lymphostasis and eczema on the left arm.

PMID- 1980565
TI  - Antibody prevalence against rubella among hospital personnel in Nigeria:
      implications for health care system and immunisation policy.
AB  - Among 385 sera from Nigerian hospital personnel aged 15-39 years, 289 (75%) had
      an antibody titer corresponding to immunity against rubella, compared with 346
      (90%) of the sera from Swedish women of the same age group. The frequency of high
      immune level against rubella did not change with age among Nigerians compared
      with a decrease in immunity with increasing age in the Swedish individuals. This
      probably is due to the differences between the dynamics of the development of
      natural immunity and immunity acquired through vaccination. In Nigeria, socio
      economic factors were related with the degree of immune responses while sex was
      not. The results highlight the importance of immunization among hospital
      personnel and eventual vaccination of the whole population in Nigeria and the
      continuous surveillance of rubella immunity and periodic re-evaluation of
      immunization policies.

PMID- 1980566
TI  - Echinococcus multilocularis: characterization of a DNA probe.
AB  - A 0.6 kb DNA fragment has been isolated from a genomic sublibrary of the cestode
      Echinococcus multilocularis. This DNA-fragment showed a strong hybridization
      signal to 32PdCTP labeled total DNA prepared from E. multilocularis metacestode
      material. The fragment was subcloned into the Escherichia coli vector Bluescript
      BS+ resulting in the recombinant plasmid pAL1. The recombinant parasite DNA probe
      was labeled by biotinylation and hybridized to Southern blots of resolved
      EcoRI/PstI digested genomic DNA originating from E. multilocularis, E. granulosus
      and other helminth species (Taenia hydatigena, T. crassiceps, T. saginata,
      Mesocestoides corti, Hymenolepis diminuta, Moniezia expansa). The Southern blot
      hybridization experiments revealed that the DNA probe pAL1 was specific for E.
      multilocularis and E. granulosus. By comparison of the hybridization banding
      patterns a clear discrimination between E. multilocularis and E. granulosus was
      possible at the genome level. Furthermore, pAL1 was used to detect genetic
      variation within a set of different E. multilocularis isolates which had been
      experimentally maintained in mice by parasite tissue transplantation.

PMID- 1980567
TI  - Development of cloned DNA probes for the identification of snail intermediate
      hosts within the genus Bulinus.
AB  - DNA fragments have been isolated from Bulinus cernicus and cloned in Escherichia
      coli strain JM109 using pUC18 as the vector. Four recombinant plasmids designated
      pBC123, pBC126, pBC127 and pBC134 were selected for further analysis and were
      shown by both dot and Southern blot hybridisations to have different
      specificities to species representing the four species groups of Bulinus. Non
      specific hybridisation occurred with pBC126 whereas pBC123 and pBC134 hybridised
      only to B. cernicus. Partial restriction maps of the inserts revealed sequence
      differences between pBC123 and pBC134. Intermediate specificity was shown by
      pBC127 as this probe hybridised only to DNA from snails of the B. forskalii group
      and B. truncatus of the B. truncatus/tropicus complex. The results demonstrate
      the potential of DNA probes for the identification and characterisation of
      intermediate hosts of schistosomes.

PMID- 1980568
TI  - Improved identification of Nannomonas infections in tsetse flies from The Gambia.
AB  - Trypanosomes from 36 midgut infections were isolated in procyclic culture from
      Glossina morsitans submorsitans and G. palpalis gambiensis in The Gambia. Twenty
      eight stocks (78%) were identified using DNA probes specific for: (a) Trypanosoma
      (Nannomonas) congolense savannah type, (b) T. (N.) congolense riverine-forest
      type, (c) T. (N.) simiae and (d) Trypanozoon, T. simiae and savannah type T.
      congolense were found only in G.m. submorsitans while the riverine-forest type T.
      congolense was restricted to populations of G.p. gambiensis from two isolated
      areas of relict forest: one Trypanozoon stock was isolated from G.m.
      submorsitans. T. congolense accounted for only 17% of all Nannomonas infections,
      as identified by dissection, in G.m. submorsitans. This re-emphasises the
      importance of differentiating infections below the subgeneric level when
      estimating challenge to domestic animals. T. simiae could not be distinguished
      from T. congolense by the arrangement of trypanosomes in the fly proboscis. The 8
      stocks which were not identified by DNA probes were separated into two groups on
      the basis of hybridization with total DNA probes and the cycle of development in
      experimental tsetse. One group of four isolates, all from G.m. submorsitans, was
      a new kind of Nannomonas which appeared to be common and widespread in The
      Gambia. The second group, which was found only in G.p. gambiensis, had a
      stercorarian cycle of development, maturing in the hindgut, and was
      morphologically similar to insect forms of the crocodile parasite T. grayi.

PMID- 1980570
TI  - Antibodies to Plasmodium falciparum in an indigenous population from a malaria
      endemic area of Malaysia.
AB  - Indirect fluorescent antibody (IFA) tests and enzyme-linked immunosorbent assays
      (ELISA) were used to measure antibodies to Plasmodium falciparum in an indigenous
      population in an area of Malaysia with high malaria prevalence. The results of
      three surveys were analyzed to examine the relation of these serologic measures
      with age, parasite rate, and spleen size. For children 0-4 years old, increasing
      spleen size was associated with an increasing likelihood of malaria parasitemia,
      while for 5-9 year olds the two variables were unrelated. Parasite rate declined
      with age and ELISA titre increased with age in all surveys; IFA titre was
      consistently high and did not vary with age. Neither antibody measure was
      significantly correlated with either the presence or the actual density of
      parasitemia. These antibody measures are most useful as adjuncts to the more
      traditional techniques of malaria assessment.

PMID- 1980569
TI  - The occurrence of loiasis, mansonellosis and wuchereriasis in the Jarawa River
      Valley, central Nigeria.
AB  - In a study to assess the status of filariasis in the Jarawa River Valley of the
      savanna area of Nigeria, 940 self-selected residents from 10 villages were
      examined between March 1984 and April 1987. Overall results showed 105 (11.2%)
      had microfilaraemia and/or clinical signs of filariasis. Sixty-four (6.8%) and 20
      (2.1%) persons, respectively, were infected with Mansonella perstans and Loa loa
      microfilariae (mff). Four of the 28 villagers examined had Wuchereria bancrofti
      mff in their night blood samples whereas 17 (1.8%) of all residents surveyed had
      clinical filariasis mainly due to lympho-obstructive manifestations: hydrocele (n
      = 11, 64.7%); enlargement of the inguinal nodes (n = 8, 47.1%) and elephantiasis
      (n = 2, 11.8%).

PMID- 1980571
TI  - Large-scale rearing of Glossina longipennis in the laboratory.

PMID- 1980572
TI  - Efficacy of low doses of praziquantel in taeniasis.
AB  - Early experimental studies suggested that doses of 1 to 5 mg of praziquantel
      (PZQ) per kg are effective against several intestinal cestodiases. The usually
      recommended single dose of PZQ in human taeniasis is 5 or 10 mg/kg. A study in T.
      saginata taeniasis showed a full efficacy at a dose of 2.5 mg/kg. A field study
      confirmed that a dose between 3.4 and 7.5 mg/kg was effective in expulsion T.
      solium tapeworms in man. A dose of 2.5 mg of PZQ per kg would be safer and more
      economical in population-oriented interventions aiming at control of T. solium
      taeniasis in man.

PMID- 1980573
TI  - Clinical implications of delayed growth of the Lyme borreliosis spirochete,
      Borrelia burgdorferi.
AB  - Lyme borreliosis, a spirochetal infection caused by Borrelia burgdorferi, may
      become clinically active after a period of latency in the host. Active cases of
      Lyme disease may show clinical relapse following antibiotic therapy. The latency
      and relapse phenomena suggest that the Lyme disease spirochete is capable of
      survival in the host for prolonged periods of time. We studied 63 patients with
      erythema migrans, the pathognomonic cutaneous lesion of Lyme borreliosis, and
      examined in vitro cultures of biopsies from the active edge of the erythematous
      patch. Sixteen biopsies yielded spirochetes after prolonged incubations of up to
      10.5 months, suggesting that Borrelia burgdorferi may be very slow to divide in
      certain situations. Some patients with Lyme borreliosis may require more than the
      currently recommended two to three week course of antibiotic therapy to eradicate
      strains of the spirochete which grow slowly.

PMID- 1980574
TI  - Trypanosoma brucei evansi: dyskinetoplasia and loss of infectivity after long
      term in vitro cultivation.
AB  - Bloodstream forms of a stock of Trypanosoma brucei evansi were propagated in
      vitro for more than 14 months. After that period, all organisms were
      dyskinetoplastic and had lost their infectivity for mice. An increase in
      diminazene aceturate resistance in vitro was observed whereas the susceptibility
      to isometamidium chloride, quinapyramine sulphate and suramin was unaltered.
      Trypanosomes derived from the long term culture had a surface coat.

PMID- 1980575
TI  - Cimetidine's low price: can we afford it?

PMID- 1980576
TI  - Stability of nizatidine in extemporaneous oral liquid preparations.
AB  - The stability of nizatidine in extemporaneous oral liquid preparations stored at
      room and refrigerated temperatures was studied. Preparations containing
      nizatidine in a final concentration of approximately 2.5 mg/mL were made by
      mixing the contents of a 300-mg nizatidine capsule with commercial juices
      (Gatorade, Stokely-Van Camp; Cran-Grape, Ocean Spray; apple juice, Sundor Brands;
      and V8 vegetable juice, Campbell Soup) and with aluminum hydroxide-magnesium
      hydroxide suspension (Maalox, Rorer). A control solution was prepared in water.
      Samples of each preparation were stored at 15-30 degrees C and at 5 degrees C.
      Initially and after 4, 8, 24, and 48 hours of storage, the samples were visually
      inspected, tested for pH, and analyzed in triplicate by high-performance liquid
      chromatography for nizatidine content. No appreciable changes in appearance or pH
      occurred. The only extemporaneous preparations with greater than 10% loss of
      nizatidine potency at 48 hours were the Cran-Grape and V8 preparations at room
      temperature. There was no correlation between pH of the preparations and changes
      in drug concentration. In the Maalox and V8 preparations, the drug powder did not
      dissolve uniformly. In all the preparations tested, nizatidine was stable for at
      least eight hours at refrigerated and room temperatures. In all except the Cran
      Grape and V8 preparations, the drug was stable for 48 hours under both storage
      conditions.

PMID- 1980577
TI  - Predictability of difficult laryngoscopy in patients with long-term diabetes
      mellitus.
AB  - The laryngoscopic conditions of 62 diabetic patients who underwent renal
      transplantation or vitrectomy were studied. Anaesthesia was induced with fentanyl
      and a sleep dose of thiopentone. Conditions for direct laryngoscopy after 0.1
      mg/kg vecuronium were scored from 0 to 3 (easy-very difficult). All patients gave
      their palm prints after operation which were scored: 0, phalangeal areas
      completely visible; 1, phalangeal areas partly visible; 2, phalangeal areas
      hardly visible; 3, only fingertips printed. The incidence of difficult
      laryngoscopy was 31%. The higher the scores in the palm test, the more difficult
      was the laryngoscopy. The correlation coefficient between these two factors was r
      = 0.6 (p less than 0.001). Our study shows that joint rigidity possibly caused by
      tissue glycosylation may also involve laryngeal and cervical areas resulting in a
      strenuous laryngoscopy. A defective palm print is a warning sign for difficult
      laryngoscopy.

PMID- 1980578
TI  - [The dose-response relationship and time course of the neuromuscular blockade by
      alcuronium].
AB  - Although alcuronium has been in clinical use for almost 40 years, there is still
      considerable controversy in the literature regarding its neuromuscular blocking
      potency, the time course of the drug action and the side effects. The aim of this
      study was to investigate the dose-response relationship of alcuronium and to
      compare the time course of its neuromuscular effects with vecuronium following
      intubation doses of both compounds. METHODS. The study was carried out in two
      parts. In the first part 60 patients and in the second part 30 consenting ASA
      class I or II patients 20-60 years of age were included. The patients were
      undergoing elective gynecological or intra-abdominal operations. In the first
      part the patients received six different doses of alcuronium (60, 90, 120, 150,
      180 or 210 micrograms/kg) in order to establish its dose-response relationship.
      Each dose was administered to ten patients. In the second part patients received
      either 300 micrograms/kg alcuronium (n = 15) or 100 micrograms/kg vecuronium (n =
      15), and the time course of these two compounds (onset time, duration 25%,
      duration 75% and the recovery index) were compared. To test the reversibility,
      ten patients in each group received 30 micrograms/kg neostigmine at 25% recovery
      of T1. The neuromuscular effects of alcuronium and vecuronium were quantitated by
      EMG using the DATEX relaxograph. RESULTS. The log-logit analysis of the dose
      response data revealed an ED50 of 111 micrograms/kg and an ED95 of 250
      micrograms/kg, which is in reasonable agreement with the measured effects
      following 120 micrograms/kg and 210 micrograms/kg alcuronium, resulting in 52 +/-
      21% and 96 +/- 4% T1 depression, respectively. The onset time, duration 25%,
      duration 75% and spontaneous recovery index following 300 micrograms/kg
      alcuronium (5.0 +/- 3.4 min, 62 +/- 25 min, 119 +/- 38 min and 58 +/- 34 min)
      appeared to be significantly longer (P less than 0.05) than those observed after
      100 micrograms/kg vecuronium (3.2 +/- 1.2 min, 33 +/- 7 min, 49 +/- 9 min and 18
      +/- 7 min), respectively. The most striking finding of this study is the enormous
      individual variations observed in both neuromuscular potency and the time course
      of action of alcuronium. Following 150 micrograms/kg (routinely employed in daily
      clinical practice), the magnitude of T1 depression ranged between 19% and 100%.
      The same vast individual variations were observed in the time course of action
      following 300 micrograms/kg of alcuronium. The onset time, duration 25%, duration
      75% and spontaneous recovery index ranged between 1.3 and 14 min, 22 and 110 min,
      93 and 186 min and 32 and 116 min, respectively. CONCLUSIONS. The ED50 and ED95
      values for alcuronium found in this study are in the same order of magnitude as
      106.8 micrograms/kg and 135 micrograms/kg for ED50 and with 280 micrograms/kg for
      ED95, respectively, as reported by others. The long duration with slow recovery
      and the wide individual variation in the neuromuscular effects observed in our
      study have been reported earlier. Based on the above observations and because of
      the availability of better alternatives with fewer side effects, we conclude that
      alcuronium should be added to the list of obsolete neuromuscular blocking agents,
      together with gallamine and d-tubocurarine.

PMID- 1980579
TI  - The effect of dopexamine HCl upon collateral perfusion of the acutely ischemic
      myocardium in anesthetized dogs.
AB  - The effects of low-dose (10(-9) and 3 x 10(-9) mole/kg/min) infusions of
      dopexamine HCl, a new synthetic catecholamine with beta 2-adrenergic and DA1
      dopaminergic agonostic actions, was tested in anesthetized dogs, with and without
      acute ligation of the left anterior descending coronary artery. The infusions
      caused diastolic arterial blood pressure to fall by 12 +/- 4 and 23 +/- 5 mmHg,
      respectively. Microsphere-estimated collateral blood flow to the ischemic
      myocardium did not change significantly during the drug infusions. The findings
      suggest that low doses of dopexamine HCl do not cause coronary "steal" from
      acutely ischemic myocardium.

PMID- 1980580
TI  - [Anesthetics responsible for anaphylactic shock. A French multicenter study].
AB  - Combined allergological and anaesthetic consultations have been started in the
      last few years in eight French Teaching Hospitals so as to explore peranaesthetic
      anaphylactoid shocks. A survey was carried out in these centers in order to
      collect patients investigated with the same protocol, for the assessment of the
      incidence of anaphylaxis in France, as well as the involved drugs. Investigations
      were always carried out at least 6 to 8 weeks after the accident. The tests used
      to diagnose IgE-dependent anaphylaxis were skin tests (prick and intradermal
      tests, carried out in all eight centers), the radioimmunological assay of
      specific anti-quaternary ammonium IgE, together with an inhibition test with
      thiopentone and propofol (six centers), leukocyte histamine release (five
      centers) and human basophil degranulation tests (three centers) for those drugs
      for which no specific antibody assay exists. The collected data involved 1,240
      patients, investigated within the last four years. Anaphylaxis was diagnosed in
      821 patients (66.2%). Muscle relaxants were responsible in 668 cases (80% of
      cases of anaphylaxis). Suxamethonium was the main cause (54.3% of shocks due to
      muscle relaxants), followed by vecuronium (15.3%). General anaesthetics
      (hypnotics and benzodiazepines) were responsible for 9.2% of all cases of
      anaphylaxis opioids for 2.6%. There were only three cases of shock due to local
      anaesthetic agents. Latex and ethylene oxide are becoming increasingly involved.
      It would therefore seem mandatory to carry out after any anaphylactoid accident
      an assessment with sensitive and specific tests for anaphylaxis. Diagnosing
      anaphylaxis means that the involved drug should be used never again in that
      patient. Because muscle relaxants are by far the most involved drugs,
      anaesthetists should use them only when really required.

PMID- 1980581
TI  - [Asthma and gastroesophageal reflux. Outcome of asthma after longterm medical
      treatment of the reflux].
AB  - Over one half of the cases of chronic severe childhood asthma, refractory to
      conventional therapy and without other over aetiology, are associated to
      gastroesophageal reflux (GER). The aetiopathogenic role of GER in asthma is
      uncertain, and is only confirmed when therapy of the former induces evident
      improvement of the latter. We have instituted medical antireflux therapy over two
      years in 17 patients (17.6%) became asymptomatic after less than three months of
      therapy, and a further four (23.5%) by the sixth month. Seven patients showed
      clinical improvement by the third month (41%) and even a greater one by the sixth
      month, only very slight symptoms persisting thereafter. In three cases (17.6%)
      there was no improvement after two years of outcome of asthma and the persistence
      or not of pathological between the outcome of asthma and the persistence or not
      of pathological 24-hour pHmetry. On the contrary. macroscopic oesophagitis
      disappeared in the cases of asthma with good outcome, but persisted in all the
      cases who remained symptomatic. In conclusion, we consider that medical
      management of GER associated to asthma should be maintained for at least six
      months (if the clinical course so permits) before considering a surgical
      indication.

PMID- 1980582
TI  - Complementation of a pleiotropic Nif-Gln regulatory mutant of Rhodospirillum
      rubrum by a previously unrecognized Azotobacter vinelandii regulatory locus.
AB  - A spontaneous pleiotropic Nif- mutation in Rhodospirillum rubrum has been
      partially characterized biochemically and by complementation analysis with
      recombinant plasmids carrying Azotobacter vinelandii DNA in the vicinity of ORF12
      [Jacobson et al. (1989) J. Bacteriol 171: 1017-1027]. In addition to being unable
      to grow on N2 as a nitrogen source the phenotypic characterization of this and
      other metronidazole enriched spontaneous mutants showed (a) no nitrogenase
      activity, (b) the absence of NifHDK polypeptides, (c) a slower growth rate on
      NH4+, (d) approximately 50% higher glutamine synthetase (GS) activity than the
      wild-type, which was repressible, (e) an inability to switch-off GS activity in
      response to an NH4+ up-shift, and (f) an inability to modify (32P-label) the GS
      polypeptide. The apparent relationship between the absence of nifHDK expression
      and the absence of GS adenylylation cannot be explained in terms of the current
      model for nif gene regulation. However, R. rubrum transconjugants receiving A.
      vinelandii DNA which originated immediately upstream from nifH, restored all
      aspects of the wild-type phenotype. These data suggest a here-to-fore
      unrecognized relationship between nif expression and GS switch-off
      (adenylylation) activity, and the existence of a previously unidentified
      regulatory locus in Azotobacter that complements this mutation.

PMID- 1980583
TI  - Measurement of carvedilol enantiomers in human plasma and urine using S-naproxen
      chloride for chiral derivatization.
AB  - The enantiospecific procedure for assaying carvedilol includes the extraction of
      the drug from plasma or urine with diisopropylether after alkalization of the
      sample with pH 9.8 buffer. After evaporation of the org. solvent a chiral
      derivatization is performed using S-(+)-naproxen chloride. The HPLC separation of
      the diastereomeric amides is possible on a silica gel stationary phase with a
      mixture of n-hexane, dichloromethane, and ethanol as mobile phase. Detection of
      the products is performed by fluorescence measurement at 285/355 nm. Preliminary
      pharmacokinetic studies after i.v. infusion of racemic compound to healthy
      volunteers showed that the concentrations of the R-(+)-enantiomer exceeded those
      of the S-(-)-enantiomer. Overall, both carvedilol enantiomers exhibited a high
      clearance with preference for the S-enantiomer. The difference was even more
      expressed after p.o. dosage indicating a stereoselective first-pass effect with
      higher extraction of the levorotatory enantiomer, which is more potent with
      respect to beta-adrenoceptor antagonistic activity.

PMID- 1980584
TI  - Synthesis of transmitter glutamate and the glial-neuron interrelationship.
AB  - Glutamate in glutamatergic neurons exists in a cytosolic pool, as well as a
      transmitter pool, which is assumed to be localized in synaptic vesicles.
      Transmitter glutamate released from glutamatergic neurons is taken up by both
      neurons and glial cells, giving rise to a flux of glutamate from neurons to
      astrocytes. In astrocytes, glutamine is formed from glutamate by the glial
      specific enzyme glutamine synthetase (EC 6.3.1.2). Glutamine diffuses back to
      neurons, where glutamate is formed by phosphate-activated glutaminase (EC
      3.5.1.2). However, this cycle is not stoichiometric, and glutamine obtained from
      glial cells cannot replenish all transmitter glutamate lost from neurons. 2
      Oxoglutarate is another putative precursor for transmitter glutamate. Net
      synthesis of citric acid cycle intermediates is dependent on carbon dioxide
      fixation to pyruvate, catalyzed by pyruvate carboxylase (EC 6.4.1.1). Since this
      enzyme is exclusively glial, a net flow of citric acid cycle intermediates from
      glial cells to neurons probably exists. The quantitative contribution of each
      transmitter precursor may not be the same in different regions of the brain and
      may vary with the metabolic state of the neuron. The pool of transmitter
      glutamate is most likely regulated by the activity of glutamate-forming enzymes
      in the nerve terminal, and/or by uptake/release of glutamate and glutamate
      precursors through the synaptosomal plasma membrane.

PMID- 1980585
TI  - Interrelationship between glutamate and membrane-bound ATPases in nerve cells.
AB  - Plasma membrane potential generated by Na+, K(+)-ATPase provides the driving
      force for high-affinity, Na(+)-dependent uptake of glutamate into the cytoplasm
      of glutamatergic nerve endings and glial cells. Ca2(+)-calmodulin-dependent
      ATPase in the plasma membrane and Ca2(+)-ATPase in the endoplasmic reticulum
      influence the intracellular [Ca2+] and, therefore, the exocytotic release of
      neurotransmitter glutamate. The membrane potential across the membrane of the
      synaptic vesicles, generated by a H(+)-ATPase, provides the driving force for
      synaptic vesicular uptake of glutamate as well as that of GABA and glycine.
      Hypoxia and ischemia lead to release of glutamate, perhaps in consequence of an
      increased endogenous pool of glutamate and/or lack of substrate (ATP) for the
      ATPases. This release, rather than being exocytotic, is believed to result mainly
      from a reversal of the Na(+)-dependent high-affinity glutamate transporter in the
      plasma membrane.

PMID- 1980586
TI  - Present concepts in the adult respiratory distress syndrome (ARDS). Proceedings
      of a symposium. Lausanne, Switzerland, June 1989.

PMID- 1980587
TI  - Present role of sleep study in lung disease: Methods and application in adults.
      Report of a workshop. October 6-8, 1988, Veruno (Novara), Italy. Proceedings.

PMID- 1980589
TI  - Novel approaches to the endocrine therapy of breast cancer.

PMID- 1980588
TI  - Differentiation of cultured human breast cancer cells (AU-565 and MCF-7)
      associated with loss of cell surface HER-2/neu antigen.
AB  - The relationship between terminal cell differentiation and changes in the
      subcellular levels of the HER-2/neu antigen was investigated in cultured human
      breast cancer cells: AU-565 cells (which overexpress the HER-2/neu gene) and MCF
      7 cells (which do not overexpress this gene). Differentiation was achieved by
      treating the cells with mycophenolic acid (MPA), phorbol 12-myristate 13-acetate
      (PMA), retinoic acid (RA), or the TA-1 monoclonal antibody to the extracellular
      domain of the HER-2/neu protein. Ten to twenty percent of the cells in untreated,
      sparsely growing AU-565 cultures exhibited morphological maturation characterized
      by large lacy nuclei surrounded by sizable flat cytoplasms. A fraction of these
      cells harbored milk factors such as casein and large lipid droplets. Treatment of
      the AU-565 cells for 4 d with 9 microM MPA, 1.6 nM PMA, 2.5 microM RA, or 1
      microgram/mL TA-1 antibody resulted in cell growth inhibition and an increase in
      the percentage of cells (48-97%) that exhibit a mature phenotype. MCF-7 cells
      were also susceptible to differentiation by MPA and RA, but to a lesser degree
      than the AU-565 cells. Differentiation in the AU-565 and MCF-7 cells was
      associated with reduced immunostaining for the HER-2/neu protein at the cell
      surface membrane and with a transient increased diffuse immunostaining for this
      protein in the cytoplasm.

PMID- 1980591
TI  - [Alveolo dental injuries in children].
AB  - The frequency of alveolo-dental traumas in children necessitates a thorough study
      of their etiopathogenesis, diagnosis and therapy. The paper describes the
      authors' personal experience.

PMID- 1980590
TI  - [Tumor markers in liver metastases of colorectal carcinoma].
AB  - Colorectal cancer is a potentially curable tumour when diagnosed in the early
      stages. In order to improve the results obtained up to now, we propose
      application of a diagnostic program among patients who undergo curative resection
      for colorectal adenocarcinoma, which would consist of using a panel of tumor
      markers, in combination with endoscopic, histologic and ultrasonographic
      diagnostic methods. For this study we studied 105 patients, divided into two
      groups: A) Group 1: 30 control patients. B) Group 2: 75 patients diagnosed as
      having colorectal cancer. We performed the preoperative determination of a series
      of tumor markers (CEA, CA 19.9, GGT and PHI), endoscopy/biopsy and hepatic
      ultrasonography on these patients. Our results suggest that the design of the
      preoperative diagnostic program makes early detection of hepatic metastases
      possible. The tumor marker panel combination provided a visible increase in
      sensitivity for detecting hepatic metastases.

PMID- 1980592
TI  - [Dental-legal report for evaluation of dental injuries of traumatic origin].

PMID- 1980593
TI  - [Private insurance protection for tooth injuries in a school setting. Current
      status and trends].

PMID- 1980595
TI  - Manpower development opportunities in the Pacific: a call for resolve and
      strategic action.

PMID- 1980594
TI  - [Medico-legal and medico-social aspects of evaluation of dental injury in civil
      disability].

PMID- 1980596
TI  - World declaration on the survival, protection and development of children. World
      Summit for Children. United Nations, New York.

PMID- 1980597
TI  - Cell-cycle regulation of insulin-stimulated tyrosine aminotransferase activity in
      rat hepatoma cells.
AB  - Amongst the proteins that are subjected to variation during the cell division
      cycle few are under hormonal regulation. The variation in amount of tyrosine
      aminotransferase (TAT) in the hepatic tissue is under the control of glucagon,
      glucocorticoids and insulin. It has been reported that the inducibility of TAT
      activity by dexamethasone in rat hepatoma (HTC) is limited to the late G1 and the
      S portions of the cell cycle. Evidence is presented in this report that in the
      rat hepatoma Fao, insulin (which has the capability to promote both cell growth
      and hormonal effects via its own receptors) modulates the TAT activity during the
      cell cycle. The maximal insulin-stimulated induction of TAT activity was observed
      at the end of the G1 phase and then decreased as cells progressed through their
      mitotic cycle. The number of insulin binding sites per cell was decreased by only
      30% during the same period of time. Furthermore, the extent of receptor
      autophosphorylation decreased in the same proportion, suggesting that insulin
      receptors remained functional through the whole cell cycle. In fact, another
      insulin-stimulated cellular function, neutral amino-acid transport, was not
      modified as cells progressed into the S phase. Hydroxyurea, which is known to
      prevent cell progression into the S phase, stabilized the insulin-induced TAT
      activity at its maximal level for several hours. Reciprocally, removal of
      hydroxyurea resulted in a concomitant decrease in TAT activity and reinitiation
      of DNA synthesis.

PMID- 1980598
TI  - Exercise capacity, hemodynamic, and neurohumoral changes following acute and
      chronic administration of flosequinan in chronic congestive heart failure.
AB  - We evaluated the responses to 90 minutes and 8 days of therapy with a new long
      acting vasodilator flosequinan in ten patients with moderate chronic congestive
      heart failure in an open, uncontrolled study. Acute administration of 100 mg
      orally resulted in a decrease of preload, with a reduction of left ventricular
      end-diastolic volume, left ventricular end-diastolic pressure, pulmonary
      capillary wedge pressure, and right atrial pressure. Following the acute
      administration, we found no significant changes of heart rate, cardiac index,
      stroke volume, peripheral vascular resistance, ejection fraction, and dp/dt.
      Chronic application for 8 days (100 mg/day) showed persistent effects on preload,
      with a significant decrease of pulmonary capillary wedge pressure, right atrial
      pressure, and pulmonary arterial pressure. After 8 days of treatment, cardiac
      index was significantly increased from 2.2 +/- 0.2 l/min/m2 to 2.8 +/- 0.2
      l/min/m2 (p = 0.013) and stroke volume from 57 +/- 10 ml to 74 +/- 9 ml (p =
      0.022). Peripheral vascular resistance decreased by ml (p = 0.022). Peripheral
      vascular resistance decreased by 28%. After 8 days, bicycle exercise capacity
      increased significantly from 383 +/- 44 sec to 422 +/- 43 sec (p = 0.01) and the
      patients were able to increase their walking distance over a 6-minute exercise
      test from 426 +/- 46 m to 477 +/- 33 m (p = 0.007), with a concomitant decrease
      of dyspnea (p = 0.013). Plasma renin concentration showed only a rise 90 minutes
      after the acute administration on day 8 of the study, and atrial natriuretic
      peptide and 6-keto-prostaglandin F1-alpha decreased significantly.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1980599
TI  - Induction of cell differentiation in melanoma cells by inhibitors of IMP
      dehydrogenase: altered patterns of IMP dehydrogenase expression and activity.
AB  - To study the induction of differentiation in human melanoma cells, we treated 12
      melanoma cell lines with mycophenolic acid and tiazofurin, inhibitors of IMP
      dehydrogenase (IMPDH). In all cell lines studied, both agents inhibited cell
      growth and increased melanin content. However, the degree of growth inhibition
      did not necessarily correspond to the increase in melanin content. A detailed
      analysis of the HO and SK-MEL-131 cell lines indicated that mycophenolic acid and
      tiazofurin caused a time- and dose-dependent increase in the expression of a
      series of other maturation markers, including formation of dendrite-like
      structures, tyrosinase activity, and reactivity with the CF21 monoclonal
      antibody. The growth inhibition and melanogenesis induced by the IMPDH inhibitors
      was abrogated by the addition of exogenous guanosine. No such effect was observed
      after treatment of the cells with phorbol 12-myristate 13-acetate or retinoic
      acid, two other inducers of differentiation in these cells. The mycophenolic acid
      and tiazofurin-treated cells also showed an increased level of IMPDH mRNA and
      protein, perhaps because of compensation for the inhibitor-mediated decrease in
      IMPDH activity. In contrast, treatment with phorbol 12-myristate 13-acetate or
      retinoic acid resulted in decreased levels of IMPDH mRNA and protein. The lack of
      a consistent pattern of IMPDH expression in the cells treated with IMPDH
      inhibitors and phorbol 12-myristate 13-acetate or retinoic acid suggests that the
      altered expression of IMPDH is not a general requirement for the induction of
      cell differentiation in these cells. Our results also suggest that IMPDH
      inhibitors may provide a useful approach to circumvent the differentiation block
      in melanoma.

PMID- 1980601
TI  - Lack of evidence for autocrine feedback regulation by somatostatin in
      somatostatin receptor-containing meningiomas.
AB  - The somatostatin (SS), the SS mRNA, and the SS receptor contents were measured
      and compared in 25 human meningiomas. The SS tissue content, measured with
      radioimmunoassay, amounted to 2.89 +/- 0.82 pg/mg tissue (mean +/- SEM). The SS
      mRNA levels visualized by in situ hybridization using a 32P-labeled synthetic
      oligonucleotide probe were undetectable in all cases. SS receptors were measured
      with autoradiography using the octapeptide SS analogue 125I-204-090 as
      radioligand and were found to be present in high density in all meningiomas. For
      comparison, three SS-producing tumors, i.e., two human medullary thyroid
      carcinomas and one neuroendocrine gut tumor, were shown to have a high level of
      immunoreactive tissue SS, reaching, respectively, 2807, 401, and 22 pg/mg tissue,
      as well as moderate to high levels of SS mRNA detected with in situ
      hybridization. It can be concluded that meningioma tissue is not synthesizing
      significant amounts of SS in situ and that the low amount of tissue SS found in
      these tumors is likely to be due to SS transported there from a distant source,
      via blood, cerebrospinal fluid, or axons from nerve fibers terminating in this
      tissue. The high number of SS receptors found in meningiomas is therefore
      unlikely to be regulated by an autocrine SS production from the meningioma tissue
      itself but rather from another, unknown distant SS source.

PMID- 1980600
TI  - Isolation of novel complementary DNA clones from T lymphoma cells: one encodes a
      putative multiple membrane-spanning protein.
AB  - Five novel complementary DNA (cDNA) clones which are differentially expressed
      between two closely related T lymphoma cell clones were isolated using
      subtraction-enriched differential screening. SL12.4 cells, from which the cDNAs
      were isolated, have characteristics of thymocytes at an intermediate stage in
      development and cause prominent extranodal ovarian tumors in syngeneic animals. A
      sister cell clone, SL12.3, derived from the same tumor, has a distinct phenotype
      and causes more aggressive, diffuse lymphomas. Four of the five novel genes are
      expressed in normal thymus, activated spleen cells, or gut-associated lymphoid
      tissue. The DNA sequence and predicted protein sequence are presented for one of
      the novel cDNA clones. This novel cDNA clone detects mRNA in normal thymus, gut
      associated lymphoid tissue, and ovarian tissue. The predicted protein has four
      putative transmembrane-spanning regions. The expression of the transcript is
      repressed in somatic cell hybrids formed from SL12.4 cells fused with three
      different T lymphoma cell lines which lack detectable mRNA complementary to the
      novel cDNA clone. This trans-negative regulation suggests that the expression of
      the gene is regulated by repressional mechanisms.

PMID- 1980602
TI  - Regulation of the epidermal growth factor receptor gene expression in a
      morphological variant isolated from an epidermal growth factor receptor-deficient
      small cell lung carcinoma cell line.
AB  - Most cell lines derived from small cell lung carcinoma grow in an anchorage
      independent manner; they neither possess epidermal growth factor binding activity
      nor express epidermal growth factor receptor (EGFR) mRNA. A variant AD320, which
      grew in an anchorage-dependent manner with altered morphology, was isolated from
      the small cell lung carcinoma cell line Lu134 by treatment with the demethylating
      agent 5-azacytidine. The analysis, using methylation-sensitive restriction
      enzymes, revealed that the methylation pattern was altered only in the structural
      region of the EGFR gene; EGFR mRNA and epidermal growth factor binding activity
      could be detected in the variant. In addition, drastic changes in gene expression
      including a decrease of creatine kinase B mRNA and an increase of c-myc mRNA were
      observed. The EGFR in the variant appeared to be an active part of the
      transmembrane signaling machinery since c-fos and c-jun mRNA accumulated after
      epidermal growth factor treatment, followed by EGFR and c-myc mRNA accumulation.
      A potent tumor promoter, 12-O-tetradecanoylphorbol-13-acetate, also induced EGFR
      mRNA. Thus, the inducible regulatory mechanism for the EGFR gene was activated in
      the variant even though the EGFR gene was constitutively expressed.

PMID- 1980603
TI  - The p49/TaqI Y-specific polymorphisms in three groups of Indians.
AB  - The TaqI/p49 Y-specific RFLPs were studied in 98 Indians coming from 3 locations
      in the country. A new allele (G0) and five new haplotypes (XX-XXIV) were found,
      not present in Caucasians and in Africans. In the genealogy of haplotypes, the
      new Indian haplotypes appear grouped together, and all Indian haplotypes occupy
      an intermediate position between Caucasian and African haplotypes.

PMID- 1980605
TI  - Sclerally directed processes of dopaminergic interplexiform cells reach the outer
      nuclear layer in rat and monkey retina.
AB  - Tyrosine hydroxylase-immunolabeled wholemounts and sections of rat and monkey
      retina were observed at both the light- and electron-microscopic level. Small
      processes derived from sclerally directed processes of dopaminergic
      interplexiform cells were observed ascending to the outer nuclear layer where
      they were distributed between photoreceptor cells. A role in the regulation of
      disc shedding and/or melatonin biosynthesis is proposed for dopamine released at
      this level.

PMID- 1980604
TI  - Regional distribution of cystic fibrosis linked DNA haplotypes in Italy, a
      collaborative study.
AB  - In view of the reported variations of cystic fibrosis (CF) associated haplotypes
      among populations, a detailed analysis of the distribution of two tightly linked
      DNA markers (Xv-2c and KM.19) in 18 Italian regions was performed. Haplotypes
      were determined for 405 CF chromosomes carrying the mutation, and showed
      significant heterogeneity between the North, Center, and South of Italy and the
      island of Sardinia. KM.19/PstI Restriction Fragment Length Polymorphism (RFLP)
      showed significant heterogeneity in these four areas, and was statistically
      correlated with the geographic distribution of the disease, while Xv-2c/TaqI
      polymorphism, like the haplotypes of normal chromosomes, was more uniformly
      distributed over the same four areas. Correlation coefficients between the
      markers and the mutation have been used to obtain additional indications on the
      physical distance between the markers and the fibrosis locus.

PMID- 1980606
TI  - No evidence for loss of alleles at 11p in HBV negative hepatocellular carcinomas.
AB  - The aim of the present study was to determine whether loss of DNA sequences at
      the chromosome arm 11p, where presumed tumor suppressor genes are located, might
      occur in hepatocellular carcinomas (HCCs) of hepatitis B virus (HBV) negative
      patients. Normal liver and HCC genotypes were compared at 6 loci on 11p with 7
      polymorphic probes detecting 10 restriction length polymorphisms (RFLPs). Each of
      the 8 paired normal-tumor tissue samples was informative for at least three
      different loci on 11p13-pter. None of them showed loss of constitutional
      heterozygosity for those markers. The retainment of 11p alleles suggests that
      mechanisms other than loss of tumor suppressor genes on llp are involved in
      hepatocarcinogenesis of HBV negative patients.

PMID- 1980607
TI  - Cytogenetics and DNA amplification in colorectal cancers.
AB  - In vitro cultivated cells of 28 colorectal cancers were analyzed for chromosomal
      abnormalities that might signal amplification of DNA, either as double minutes
      (DMs) or homogeneously staining chromosomal regions (HSRs). Cells derived from 18
      tumors showed DMs in 10 to 100% of all metaphases examined. Surveys that employed
      a panel of available oncogene probes failed to detect amplification of a known
      cellular oncogene with the exception of three cases where the ERBB2 gene was
      amplified. In one of these three cases neither DMs nor HSRs were detectable. Our
      studies show that from 28 lines established in culture, 19 (68%) show
      amplification of DNA, and indicate that DNA amplification is a frequent genetic
      alteration in colorectal cancers in addition to other genetic changes.
      Amplification is correlated with high Dukes stage, but not with histological
      grade. The identity of the amplified DNA remains to be established for most
      cases.

PMID- 1980608
TI  - Molecular evaluation of abnormalities of the short arm of chromosome 1 in
      neuroblastoma.
AB  - Cytogenetic analyses have documented the consistent deletion of part of the short
      arm of chromosome 1 in neuroblastoma cells suggesting the presence of a
      suppressor gene in this chromosomal region. To determine, the smallest region of
      deletion overlap at the molecular level on independently derived tumors and to
      define the location of the breakpoints more precisely, Southern analyses were
      performed on a somatic cell hybrid panel containing the normal and altered
      chromosomes 1 from seven neuroblastoma lines. By this method we were able to
      analyze a panel of 20 cloned sequences and two isozymes to determine the location
      of the breakpoints. Our findings indicate that the proximal breakpoints of
      chromosome 1 deletions ranged over a distance of more than 50 cM with the most
      distal deletion breakpoint occurring between MYCL1 and D1S57. In addition, using
      restriction fragment length polymorphisms, it was determined that in at least
      three of the five cell lines in which MYCL1 was deleted from a chromosome 1, the
      gene was translocated to another chromosome thus retaining the diploid
      complement. We propose that the neuroblastoma susceptibility gene is located
      distal to MYCL1 and that there is another gene which is linked to MYCL1 that may
      be involved in this neoplasm.

PMID- 1980609
TI  - Demonstration of acquired hemizygosity and clonality in acute lymphoblastic
      leukemia with chromosome 7 abnormalities using hypervariable DNA probes.
AB  - Clonal abnormalities of chromosome(s) 7 were investigated in two patients with
      acute lymphoblastic leukemia. The abnormal karyotypes were 46,XY,
      7,del(6)(q13q21), + i(7q)/47,XY,del(6), + i(7q) in case 1, and 46,XX,
      7,t(4;11)(q21;q23), + i(7q) in case 2. DNA from leukemic tissue was investigated
      with Southern blotting using hypervariable DNA probes lambda MS31 and p lambda g3
      located on 7p and 7q, respectively. Restriction fragment length polymorphisms
      (RFLPs) were detected on the short arm in case 1 and on both arms in case 2, and
      a marked difference in intensity between the two alleles was observed. In case 1
      the acquired hemizygosity of 7p, suggested by the cytogenetic findings, was
      confirmed by Southern blotting. Thus, one chromosome 7 formed the i(7q) and the
      other No. 7 was duplicated. In case 2 the results of the Southern blotting
      indicated that the size of the clone with i(7q) was considerably greater than
      suggested by cytogenetic analysis of the few available metaphase cells.

PMID- 1980610
TI  - Loss of genetic information in central nervous system tumors common to children
      and young adults.
AB  - The clonal loss of genetic information as revealed by the comparison of normal
      and tumor DNA restriction fragment length alleles has permitted the determination
      of the genomic positions of cancer-recessive mutations. Here we have applied this
      approach to the analysis of 19 central nervous system tumors that constitute four
      histologic groups and occur most frequently in children and young adults. The
      detectable loss of genetic information from cases of medulloblastoma (11
      examined) indicates that among such tumors, loss occurs most frequently from the
      short arm of chromosome 17. For the ependymomas examined (four cases), chromosome
      22 was the preferred site for detectable loss. Analysis of pilocytic astrocytomas
      of the cerebellum (three cases) failed to reveal genetic alterations of any type
      among such tumors, a finding unique to this histologic group. The single choroid
      plexus papilloma examined demonstrated loss of genetic information from
      chromosome 3. Among the 19 tumors, multiple cases of loss were observed from
      chromosomes 10, 11, 13, and 22, and from the short arm of chromosome 17.
      Therefore, with regard to the chromosomal locations of implied tumor suppressor
      genes, these results are consistent with those described for intracranial tumors
      occurring more commonly in adults of middle to advanced age.

PMID- 1980611
TI  - Effects of anticholinergic medication on memory in schizophrenia.
AB  - Verbal memory and reaction time of ten schizophrenic patients were compared at
      two different serum anticholinergic levels. Verbal recall was worse at higher
      drug levels, while reaction time tended to be improved by anticholinergic
      treatment. Implications for studies of memory in schizophrenia are considered.

PMID- 1980612
TI  - Do neuroleptics impair learning in schizophrenic patients?
AB  - Dopamine (DA) has been shown to be involved in reward-related (incentive)
      learning but not stimulus-stimulus (s-s) associative learning. Schizophrenic
      individuals receive neuroleptics (DA receptor blockers) for therapy and therefore
      may have impaired incentive learning. To test this hypothesis, in experiment 1,
      schizophrenic outpatients receiving haloperidol or flupenthixol and matched
      controls were tested on tasks involving incentive or s-s learning. Patients were
      also given the Brief Psychiatric Rating Scale (BPRS). Results showed the patients
      to be significantly impaired in every task. However, only impairments of s-s
      learning were correlated with psychiatric state. Thus, deficits on the tasks
      involving incentive learning were interpreted as resulting from neuroleptic drugs
      rather than psychiatric state. Experiment 2 tested 26 schizophrenic inpatients
      receiving a variety of neuroleptics (converted to chloropromazine equivalency
      (CPZEQ)) on the same tasks. A blood sample was collected from the patients and
      from age-matched controls and prolactin levels were found to be significantly
      higher in the patients. Multiple regression analysis was used on patient data to
      determine whether prolactin level or CPZEQ were related to performance. It was
      found that incentive learning but not s-s associative learning was significantly
      predicted by one of these two indexes of neuroleptic drug dose. The results of
      these experiments provide some support for the hypothesis that neuroleptics might
      impair incentive but not s-s associative learning in schizophrenics. The
      observation that neuroleptics affect human incentive learning might lead to more
      efficient use of behavior modification programs in the treatment of
      schizophrenia.

PMID- 1980613
TI  - Neuroleptic drug effects on cognitive function in schizophrenia.
AB  - Neuropsychological test performance was compared in 37 neuroleptic treated DSM
      III schizophrenic patients, 27 untreated schizophrenic patients, and 27 normal
      controls. Neuroleptic treated patients performed significantly less well than
      untreated patients at recalling a complex figure, at planning on a mazes test,
      and had poorer fine motor coordination. Controls and untreated patients performed
      equally well on these tests. The results were not altered in 16 neuroleptic
      treated patients who had been prescribed low doses of benztropine, nor 38
      patients who reported prior substance abuse. Similar cognitive impairments are
      observed in Parkinson's disease and are associated with dopaminergic antagonist
      drugs in schizophrenics. Therefore, they do not comprise part of the
      Schizophrenic Deficit State. Two tests were better performed by controls than
      patients. Reaction time was slower and more variable in both treated and
      untreated patient groups than controls. The recall of paraphrased passages was
      significantly poorer in both patient groups than controls, a finding that is
      robust in subgroups matched for IQ. Neuroleptic treatment was associated with
      significantly better performance on this test.

PMID- 1980614
TI  - Lymphocyte subsets in schizophrenic disorders. Relationship with clinical,
      neuromorphological and treatment variables.
AB  - Peripheral blood lymphocyte subsets and serum immunoglobulin levels were assessed
      in 42 patients and 37 healthy controls. 24 patients were free from neuroleptic
      medication and 15 had never been treated with neuroleptics. 31 patients had a
      diagnosis of schizophrenia (DSM-III criteria) and 11 a diagnosis of a disorder of
      the schizophrenic spectrum. As compared to healthy subjects, the drug naive
      schizophrenic patient group showed an increase of T suppressor lymphocytes, while
      the drug-treated schizophrenic group showed an increase of T helper lymphocytes.
      The drug-treated schizophrenic group differed from the drug naive one relative to
      a decrease of T suppressor lymphocytes. As compared to healthy subjects, the drug
      naive spectrum disorder patients showed an increase of absolute number of
      lymphocytes, while the drug treated spectrum group showed an increase of B
      lymphocytes. These findings did not correlate with any clinical or
      neuromorphological variables taken into account.

PMID- 1980615
TI  - Association of CD2 and T200 (CD45) in mouse T lymphocytes.
AB  - A monoclonal antibody (mAb 12-15) reactive with the mouse CD2 was found to co
      precipitate a high-molecular-weight glycoprotein from mouse thymocyte, splenic
      lymphocyte, Con A blast, and T cell tumor detergent lysates which was identified
      as the leukocyte common T 200 glycoprotein (CD45). The reactivity was specific
      for CD2 since antibodies to CD3 did not co-precipitate the T200 glycoprotein. mAb
      12-15 did not react with immunoaffinity-purified T200 glycoprotein, ruling out
      the possibility that the antibody detected a cross-reactive epitope. Biochemical
      data indicated that the association of CD2 with T200 was not generated during
      lysis of the cell and that the molecular complex was non-covalently linked since
      it could be destroyed by high salt washing or boiling in SDS. Distribution
      analysis in Triton X114-H2O revealed that, in contrast to free T200 molecules,
      the complexed T200 was enriched in the detergents phase. To investigate the CD2
      T200 association in more detail at the cell surface, modulation of CD2 and T200
      was studied. Modulation could be induced on Con A blasts by monoclonal antibodies
      followed by cross-linking with a FITC-conjugated second antibody. Within 24 h the
      expression of CD2 or T200 was reduced to approximately 10-20% of the initial
      value on the majority of cells. However, two-color fluorescence showed that
      modulation of CD2 did not lead to co-modulation of CD3 or T200. A possible
      physiological role of CD2-T200 complexes is discussed.

PMID- 1980616
TI  - CD4+CD8+ murine intestinal intraepithelial lymphocytes.
AB  - We have studied a population of CD4+ intestinal intraepithelial lymphocytes using
      two-color flow cytometric analyses, and in highly purified fluorescent-activated
      cell-sorted preparations. Although CD4+ T cells present within the epithelial
      immune compartment comprised only approximately 10-20% of the total intestinal
      epithelial lymphoid cells, an unusually high proportion of those CD4+ lymphocytes
      expressed a CD4+CD8+ phenotype which is rarely encountered in peripheral T cells.
      By comparison, CD4+ lymphocytes from spleen or lymph nodes existed exclusively as
      single-positive T cells. Analyses of CD4 and CD8 expression on lymphocytes from
      Peyer's patches, the lamina propria, and IEL indicated that CD4+CD8+ lymphocytes
      were unique to the IEL. Using CD4+CD8+ preparations obtained by fluorescent
      activated cell sorting, CD4+CD8+ epithelial T cells were found also to express
      CD3 and Thy-1 surface markers. This heretofore undescribed extrathymic population
      of double-positive T cells constitutes a unique peripheral T cell subset which
      may be involved in intestinal T cell maturation and development, or could
      represent a highly specialized effector population.

PMID- 1980617
TI  - Surface expression of CD4 and Thy-1 on mouse thymic stromal cells.
AB  - Subpopulations of thymic stromal cells (TSC) and T lymphocytes have been
      antigenically defined as a basis for understanding intrathymic cellular
      communications which result in the mature T-cell repertoire. In the current study
      we present data that the markers CD4 and Thy-1, standard T lymphocyte markers in
      mice, are also expressed by subpopulations of freshly isolated and cultured TSC.
      This was shown by flow cytometric analyses and fluorescence microscopy
      respectively. Use of F(ab')2 fragments of anti-CD4 mAb demonstrated specific
      antibody binding and not that due to FcR binding. Double-labelling experiments
      illustrated that the subpopulation of CD4+ stromal cells includes cells bearing
      the MAC-1 antigen. The majority of Thy-1+ stromal cells were epithelial cells
      (determined by double-labelling cultured TSC with anti-cytokeratin); however,
      there was also a novel subpopulation of non-epithelial stromal cells present.
      Whilst actual synthesis of these glycoproteins has not yet been demonstrated,
      their existence as surface antigens on TSC to any degree could have major
      relevance to the understanding of intrathymic intercellular events. It also
      cautions that experiments on T cell lineage relationships based on in vivo
      injection of anti-CD4 antibodies be interpreted with care.

PMID- 1980618
TI  - A transfected human muscarinic receptor fails to substitute for the T cell
      antigen receptor complex in CD2-initiated signal transduction.
AB  - Several T cell surface molecules can activate signal transduction pathways that
      lead to T cell activation. Like the T cell antigen receptor (TCR), several other
      molecules, including the sheep erythrocyte receptor CD2, are able to activate the
      phosphatidylinositol (PI) signal transduction pathway upon stimulation with
      appropriate agonists. However, CD2-initiated activation of this pathway is
      dependent on the functional expression of the TCR. Since the T cell does not
      express other known receptors that activate the PI pathway independent of the
      TCR, the specificity of the CD2 requirement for a functional TCR is not known. To
      evaluate the specificity of this requirement, we examined the functional capacity
      of CD2 to activate the PI pathway in a TCR-deficient cell which had been
      transfected with a heterologous receptor, the human muscarinic subtype 1 receptor
      (HM1). HM1 is a member of the cholinergic family of receptors and is known to
      activate the PI pathway. HM1 can function in the absence of the TCR in a Jurkat
      derived T cell host. Here we demonstrate through calcium fluorimetry and PI
      metabolism assays that HM1 is unable to substitute functionally for the TCR in
      CD2-initiated signal transduction. These results suggest a specific functional
      interaction between CD2 and the TCR in CD2-mediated activation of the PI pathway
      in T cells.

PMID- 1980619
TI  - CD4 and CD8 T cells from SIV-infected macaques have defective signaling responses
      after perturbation of either CD3 or CD2 receptors.
AB  - Single-cell clones, designated E11S, C11R, and A1S, were obtained from the HuT-78
      T cell line persistently infected with an isolate of Simian immunodeficiency
      virus (SIV), SIV/Mne. The infected clones, unlike uncloned uninfected HuT-78
      cells, no longer expressed the CD4 marker and, after their CD3 receptors were
      cross-linked, had dramatically reduced intracellular free calcium ([Ca2+]i)
      responses. In one clone, E11S, the unresponsiveness was not limited to the
      inositol phospholipid pathway of signaling since a reduction in CD3-mediated
      activation of protein tyrosine kinase-dependent phosphorylation also was evident
      in this SIV-infected clone. These results led us to test whether T lymphocytes
      from animals infected with SIV had defective [Ca2+]i responses prior to
      detectable changes in CD4 levels or lymphadenopathy. The [Ca2+]i responses to
      both CD3 mAb and CD2 mAb were 10-50% less in T cells from Walter Reed stage 2
      animals than in healthy controls. This anergy was more pronounced in chronically
      infected animals progressing to Walter Reed stage 3/4. The responses of these
      animals could not be augmented even when combinations of CD3 and CD4 mAb were
      used. Both CD4+CD44lo T cells, which are not infected with SIV, and the
      CD4+CD44hi T cell subset, previously shown to be the reservoir of SIV infection
      in blood, had pronounced defective responses to CD3 mAb. Similarly, both CD4+ and
      CD8+ T cells were consistently unresponsive in chronically infected animals,
      again implying that an indirect mechanism, rather than SIV infection per se, may
      be responsible for this immune dysfunction.

PMID- 1980620
TI  - Killer T's, macrophages, and NK's. The Fourth International Cell-Mediated
      Cytotoxicity Workshop, sponsored by the Pittsburgh CancerInstitute, and the
      University of Pittsburgh Medical Health Care Division, Oglebay Park, WV, USA,
      June 10-13, 1990.

PMID- 1980621
TI  - Pathways to release. Mechanisms of Exocytosis, a Jacques Monod Conference,
      sponsored by the Centre National de la Recherche Scientifique, Aussois, France,
      June 17-23, 1990.

PMID- 1980622
TI  - The ins and outs of transposition. Molecular Mechanisms of Transposition and its
      Control, sponsored by the European Molecular Biology Organization, Roscoff,
      France, June 24-28, 1990.

PMID- 1980624
TI  - [Quantitative determination of transplantable hemopoietic stem cells by limiting
      dilution method].
AB  - The concentration of hemopoiesis restoring units (HRU) in bone marrow of mice was
      assayed by using the limiting dilution method in transplantation to lethally
      irradiated mice. 7 to 12.7 HRU were found in 10(6) bone marrow cells of CBF1 mice
      and 19.2 to 50.6 HRU in BCT6F1 mice when the survival of the recipients was
      registered in 4 weeks after transplantation. The proportion of not surviving
      recipients increased with time when marrow doses were low (2.5 X 10(4) to 2 X
      10(5) cells or 0.5-2.5 HRU per mouse) and remained stable when middle or high
      marrow doses (10(6)-10(7) cells) were used.

PMID- 1980623
TI  - [Study of dipeptidyl peptidase IV as a surface marker of human natural killer
      cells].
AB  - The enriched populations of natural killer (NK) cells have been obtained using
      two different approaches. The first one was based on the separation in a density
      gradient of Percoll and further formation of rosettes with sheep erythrocytes.
      This method allowed to isolate the population containing approximately 70% of
      CD16(+)-cells. The second approach consisted in separating lymphocytes on a flow
      cytofluorometer FACS II. Using this method the population with 80% CD16(+)-cells
      was isolated from PBMC. Studies on morphological, phenotypical and functional
      characteristics of the first population revealed that NK cells constituted 70% of
      total number of cells; T-lymphocytes, 8-lymphocytes and monocytes constituted the
      minor population (10%, 8% and 1% respectively). Activity of DPIV was determined
      on both cell populations obtained. As it was shown, approximately 27% of the
      cells isolated using percoll density gradient and 22% of the cells after the
      separation on a flow cytofluorometer carried the enzyme molecules on the cell
      surface. The results of the present study apparently indicate that part of NK
      cells (about 10%) is characterised by the presence of DPIV on the cell surface.

PMID- 1980625
TI  - Amino acid sequence of cadmium-binding peptide induced in a marine diatom,
      Phaeodactylum tricornutum.

PMID- 1980626
TI  - Qualitative and quantitative high performance liquid chromatographic analysis of
      monoamine neurotransmitters and metabolites in cerebrospinal fluid and brain
      tissue using reductive electrochemical detection.
AB  - The application of reductive coulometric electrochemical detection for analysis
      of the monoamine neurotransmitters norepinephrine, dopamine, and serotonin and
      their common metabolites in brain and cerebrospinal fluid following separation by
      isocratic high performance liquid chromatography is described. The high
      sensitivity and screening capabilities of coulometric electrodes permits the
      accurate quantitation of as little as 3-5 pg of these compounds in tissue
      following a simple single step purification procedure. Moreover, comparison of
      peak height ratios obtained from analysis of authentic reference standards and
      tissue samples at selected multiple electrode potentials provides a
      straightforward means for qualitative evaluation of peak identification and
      purity during analysis of biological samples. The method is comparatively
      inexpensive and precise within and between day coefficients of variation for most
      compounds range from 2-5%. Thirty samples can be run in duplicate in a 24 h
      period.

PMID- 1980628
TI  - Insight and psychosis.

PMID- 1980627
TI  - Monoamines and abnormal behaviour. A multi-aminergic perspective.
AB  - Classical nosology has been the cornerstone of biological psychiatric research;
      finding biological markers and eventually causes of disease entities has been the
      major goal. Another approach, designated as 'functional', is advanced here,
      attempting to correlate biological variables with psychological dysfunctions, the
      latter being considered to be the basic units of classification in
      psychopathology. Signs of diminished DA, 5-HT and NA metabolism, as have been
      found in psychiatric disorders, are not disorder-specific, but rather are related
      to psychopathological dimensions (hypoactivity/inertia, increased
      aggression/anxiety, and anhedonia) independent of the nosological framework in
      which these dysfunctions occur. Implications of the functional approach for
      psychiatry include a shift from nosological to functional application of
      psychotropic drugs. Functional psychopharmacology will be dysfunction-orientated
      and therefore geared towards utilising drug combinations. This prospect is hailed
      as progress, both practically and scientifically.

PMID- 1980629
TI  - Role of the gut proteinases from mosquito larvae in the mechanism of action and
      the specificity of the Bacillus sphaericus toxin.
AB  - Gut proteinases from larvae of mosquito species both susceptible and not
      susceptible to Bacillus sphaericus converted the 43-kDa toxin to a 40-kDa
      polypeptide exhibiting enhanced cytotoxicity to mosquito cell cultures. The toxin
      was also activated by gut proteinases from the nonsusceptible Lepidoptera
      Spodoptera littoralis in vitro and in vivo. Therefore, the specificity of
      Bacillus sphaericus toxin does not seem to be determined by gut proteinase
      action. However, susceptibility of mosquito cell cultures did not reflect the
      specificity of the toxin, which must now be investigated at the cellular level in
      the larvae.

PMID- 1980630
TI  - Structural studies of acidic polymers produced by the O23 reference strain of
      Serratia marcescens: presence of amide-linked glutamic acid.
AB  - The major fraction of an acidic galactoglucomannan present in lipopolysaccharide
      extracts from cell walls of the O23 reference strain of Serratia marcescens has
      the tetrasaccharide repeating-unit shown. In a minor fraction, L-glutamic acid
      was amide-linked to about half of the D-glucuronic acid residues. The possible
      contributions of the acidic polymers and a neutral polymer produced by the
      organism to cross-reactions with other serogroups are discussed.

PMID- 1980632
TI  - Effect of ibopamine, a dopamine congener, on arrhythmias in heart failure.
AB  - Patients with heart failure exhibit a high prevalence of both ventricular and
      supraventricular arrhythmias, and the ventricular arrhythmias are characterized
      by multiform, bigeminal and paired beats as well as nonsustained ventricular
      tachycardia. The prognosis of heart failure is severe and approximately half of
      the patients die suddenly. In view of the high prevalence of arrhythmias in heart
      failure and the complex ventricular arrhythmias, it is important to consider the
      effect of antifailure treatment on such arrhythmias. Dopaminergic drugs represent
      one interesting therapeutic alternative. Ibopamine is an orally active
      dopaminergic substance and acts mainly as a vasodilator in patients with heart
      failure. According to published investigations on ibopamine in heart failure,
      this drug does not seem to have a proarrhythmic effect.

PMID- 1980631
TI  - Pharmacological profile of ibopamine. A summary of experiments on anaesthesized
      dogs.
AB  - This review summarizes the results obtained with ibopamine on anaesthesized dogs.
      Ibopamine is a dopamine-related drug active by oral route, namely the
      diisobutyric ester of N-methyl-dopamine. Ibopamine is able to activate dopamine
      specific and adrenergic receptors in the heart and circulation, inducing a
      vasodilating activity together with a mild positive inotropic effect without
      increasing heart rate and myocardial O2 consumption. The activation of dopamine
      and adrenergic receptors mediates a direct vasodilation postjunctional DA1 and
      beta 2 receptors and an indirect vasodilation (presynaptic DA2 and alpha 2
      receptors) through the inhibition of the release in norepinephrine, the renin
      angiotensin system, and the secretion of aldosterone and vasopressin, thus
      antagonizing the neurohormonal alterations in congestive heart failure through a
      receptor mechanism. Ibopamine can also activate beta 1- and beta 2 and very
      modestly vascular synaptic alpha 1- and alpha 2-receptors, thus inducing a mild
      positive inotropic activity and avoiding a drop in arterial pressure which might
      take place in presence of the intense vasodilation induced by the drug. There is
      some difference in potency between dopamine and epinine. Epinine is the active
      metabolite of ibopamine and is more active than dopamine on DA1, DA2, alpha 1,
      alpha 2 and beta 1 and beta 2 receptors. Ibopamine can be safely associated with
      captopril and digoxin but not with nifedipine.

PMID- 1980633
TI  - Long-term treatment of congestive heart failure with oral ibopamine. Effects of
      rhythm disorders and neurohormonal alterations.
AB  - A group of 30 patients with II-III NYHA class cardiac insufficiency was treated
      with ibopamine in association with other drugs for a 6-month period. The patients
      were submitted to a 24-h ambulatory ECG Holter monitoring, chest X-ray, Doppler
      echocardiography in order to calculate total peripheral vascular resistance.
      Blood levels of aldosterone and renin-angiotensin activity in plasma were also
      measured, together with norepinephrine excretion. The measurements and recordings
      were performed in basal conditions before the trial, and were repeated after the
      first, second, third and sixth month. Laboratory tests were performed at the
      baseline and after 6 months. The results showed a significant decline in the
      number of ventricular and supraventricular ectopic beats after treatment. Heart
      rate did not change. Cardio-thoracic ratio decreased significantly along with
      peripheral vascular resistance. A very noticeable decline in all three
      neurohormonal parameters, i.e. norepinephrine excretion, blood level of
      aldosterone and renin activity in plasma was observed after 1 month's treatment,
      and this reduction was still present without any attenuation after 6 months. No
      significant changes were observed in routine laboratory tests.

PMID- 1980634
TI  - Hemodynamic and neurohumoral effects of ibopamine in patients with chronic
      congestive heart failure.
AB  - Ibopamine is a new, orally active dopamine-like drug with inotropic and
      vasoactive properties. With a predominant action on dopaminergic (DA) and beta
      receptors, ibopamine increases cardiac output, reduces peripheral vascular
      resistances and increases renal blood flow, exerting a lesser effect on preload
      parameters. This hemodynamic improvement is manifested in subjects with normal
      myocardium as well as in patients with heart failure in different stages of the
      syndrome including refractory heart failure, and it is also present after
      relatively long-term treatment without evidence of pharmacological tolerance.
      Probably in relation with DA2 activation, ibopamine also modulates the
      neurohumoral consequences of heart failure with a decrease in plasma renin
      activity and norepinephrine and aldosterone plasma levels, both acutely and after
      chronic administration, an effect that can be beneficial in the long-term
      treatment of patients with chronic congestive heart failure.

PMID- 1980635
TI  - The cytotoxic and cytolytic activity of equinatoxin II from the sea anemone
      Actinia equina.
AB  - The cytotoxic and cytolytic effects of equinatoxin II (EqT II) from the sea
      anemone Actinia equina L. were studied on exponentially growing and synchronized
      V-79-379 A cell line in culture. The cell viability test and the determination of
      the cytolytic effect by cell counting confirmed both cytotoxic and cytolytic
      activity of EqT II. Additionally, cytocidal and cytostatic effects depending on
      the toxin concentration were observed. The presence of fetal calf serum in the
      cell culture medium reduced both cytocidal and cytostatic effects by two
      magnitudes and prevented cytolysis. Combining EqT II and serum resulted in an
      insoluble complex which was cytostatic even when isolated and resuspended in the
      culture medium, while the supernatant retained both cytocidal and cytostatic
      activity. No significant difference in sensitivity between synchronized and
      exponentially growing cells could be detected after EqT II treatment.

PMID- 1980636
TI  - S phase duration measurement by combined PCNA/cyclin immunostaining and
      radioautography after a single pulse-labelling with 3H-thymidine.
AB  - A method for measuring S phase duration is described and evaluated that combines
      single pulse labelling with 3H-thymidine (TdR), detected by radioautography, and
      proliferating cell nuclear antigen (PCNA)/cyclin immunostaining to replace the
      second pulse labelling of the classical double-labelling method. Conditions were
      set up in which nuclei showing one or both types of label were readily
      distinguished, hence allowing to verify that cell fluxes in and out of S phase
      were equal. S phase durations thus measured in different tissues of the mouse
      were concordant with those obtained by the double 3H-TdR labelling or from
      labelled mitoses curves. Our method might be used with archived samples of
      methanol-fixed cells or tissues, singly labelled with 3H-TdR or with
      bromodeoxyuridine.

PMID- 1980638
TI  - Effects of meals on gastric emptying and small intestinal transit times of a
      suspension in the beagle dog assessed using acetaminophen and
      salicylazosulfapyridine as markers.
AB  - Effects of the amount and the composition of meals on gastric emptying and small
      intestinal transit times of a suspension were investigated in beagle dogs using
      acetaminophen and salicylazosulfapyridine as markers. Gastric emptying time was
      affected both by the amount and the composition of a meal; it was prolonged
      proportionally to the amount of a solid meal and varied among the 3 kinds of test
      meals of the same energy content in the following rank order: lard greater than
      skimmed milk greater than mashed potatoes. The inter-individual variation of
      small intestinal transit time in a fed state was smaller than that in a fasted
      state, whereas the mean transit times in both states were similar. Small
      intestinal transit time was not affected by the amount of the solid meal. On the
      other hand, it varied among the 3 kinds of test meals in the following rank
      order: lard greater than mashed potatoes greater than skimmed milk. It is
      noteworthy that small intestinal transit time in the beagle dog is approximately
      2 h shorter than that in humans both in fasted and fed states.

PMID- 1980637
TI  - Studies on analgesic oligopeptides. VI. Further studies of synthesis and
      biological properties of tripeptide alkylamides, Tyr-D-Arg-Phe-X.
AB  - Nine analogs based on a structure of Tyr-D-Arg-Phe-X (X = alkylamides or
      alkylhydrazide containing electron-withdrawing atoms or groups) were newly
      synthesized and their biological properties were examined by the opioid receptor
      binding properties of mu-, delta- and kappa-receptors, guinea-pig ileum (GPI)
      assay and analgesic activity in the tail pinch test after subcutaneous
      administration in mice. Analogs with X = NHCF2CF3, Sar-ol, or NH(CH2)2CN showed
      potent activities in the GPI and analgesic assays and high affinity for mu
      receptor. An analog with X = taurinamide was found to possess 4-fold higher mu
      receptor selectivity than that of [D-Ala2, MePhe4, Gly-ol5]enkephalin (DAGO). The
      receptor binding properties of previously reported analogs [Chem. Pharm. Bull.,
      33, 1528 (1985); ibid., 33, 4865 (1985); ibid., 36, 4834 (1988)] were also
      examined for overall discussion of the structure-activity relationships of this
      series of tripeptide amides.

PMID- 1980639
TI  - Efficacy of emetic and United State pharmacopoeia ipecac syrup in prevention of
      drug absorption.
AB  - The efficacy of both the emetic syrup prepared in the previous report and the
      United States Pharmacopoeia (USP) ipecac syrup concerning the prevention of drug
      absorption was investigated in 4 beagle dogs using a randomized and cross-over
      design. In order to control the intragastric pH of the beagle dogs, the
      administration of pentagastrin or hydrochloric acid (HCl)-glycine buffer (pH 1.5)
      was tested. The intragastric pH changed from 7.2 to 1.8 with the intramuscular
      administration of pentagastrin, but the primary emesis occurred more slowly. On
      the other hand, the HCl-glycine buffer (pH 1.5) gave the appropriate emesis.
      Therefore, the HCl-glycine buffer (pH 1.5) was used to control the intragastric
      pH of the beagle dogs. Acetaminophen (AcA), salicylic acid (SA) and kanamycin
      (KM) as markers were administered orally after conditioning the intragastric pH
      at 1.5. The emetic syrup or the USP ipecac syrup was then administered. The
      recovery rate of AcA and KM from vomit was 42-65%. The emetic syrup and the USP
      ipecac syrup significantly reduced the absorption of AcA from the calculation of
      pharmacokinetic parameters compared to the control syrup. It was observed that
      the absorption of cephaeline (CP) in the emetic syrup was less than that of CP in
      the USP ipecac syrup.

PMID- 1980640
TI  - Direct inhibition of pepsinogen secretion from rat gastric chief cells by
      somatostatin.
AB  - Effects of somatostatin on pepsinogen secretion was investigated in the rat in
      vivo and in vitro. In the perfused rat stomach, somatostatin inhibited
      secretagogue-induced acid secretion in dose-dependent manner. However, effects of
      somatostatin on secretagogue-induced pepsinogen secretion were obscure. To
      clarify the effects of somatostatin on the chief cells, gastric mucosal cells
      were isolated by a proteolytic enzyme. Somatostatin inhibited carbachol- and
      cholecystokinin octapeptide-induced pepsinogen secretion from dispersed gastric
      mucosal cells in a dose-dependent manner. Histamine-induced pepsinogen secretion,
      which was recovered by culturing, was also inhibited by somatostatin. These
      results suggest that somatostatin inhibits secretagogue-induced pepsinogen
      secretion directly.

PMID- 1980641
TI  - Synthesis and biological activity of [MeTyr1,MeArg7,D-Leu8]-dynorphin A(1-9)-NHEt
      and [D-Cys2-Cys5,MeArg7,D-Leu8]-dynorphin A(1-9)-NH2.
AB  - The opioid activities of [MeTyr1]-Dyn(1-7)-NH2, [MeTyr1,D-Leu8]-Dyn(1-8)-NH2,
      [MeTyr1,D-Leu8]-Dyn(1-9)-NH2, [MeTyr1,D-Leu8]-Dyn(1-10)-NH2, [MeTyr1,D-Leu8]
      Dyn(1-11)-NH2, and [MeTyr1,D-Leu8,12]-Dyn(1-13)-NH2 were examined in the
      bioassays (guinea pig ileum, mouse vas deferens and rabbit vas deferens). Because
      [MeTyr1,D-Leu8]-Dyn(1-9)-NH2 showed the most potent opioid activity of the
      peptides tested, the biological activities of two kinds of Dyn(1-9) analogues,
      [MeTyr1,MeArg7,D-Leu8]-Dyn(1-9)-NHEt and [D-Cys2-Cys5,MeArg7,D-Leu8]-Dyn(1-9)-NH2
      were determined and compared with those of [MeTyr1,MeArg7,D-Leu8]-Dyn(1-8)-NHEt
      and [D-Cys2-Cys5,MeArg7,D-Leu8]-Dyn(1-8)-NHEt in the three bioassays, in the
      receptor binding assays, and in the mouse tail pinch test after subcutaneous
      administration. The results suggest that the extension of the C-terminal in the
      peptide chain of [MeArg7,D-Leu8]-Dyn(1-8)-NH2 analogues by Arg is ineffective for
      increasing the kappa-opioid activities, kappa-receptor selectivity and/or
      analgesic effects of the peptides.

PMID- 1980642
TI  - Expression of vasopressin and opiates but not of oxytocin genes studied by in
      situ hybridization in embryonic rat brain primary cultures.
AB  - Expression of arginine-vasopressin (AVP), oxytocin (OT), dynorphin and enkephalin
      genes was studied with the in situ hybridization technique in embryonic rat brain
      serum-free cultures. Neurones were prepared from hypothalamus and
      extrahypothalamic structures of 16-day-old rat embryos. After 7 days in culture,
      AVP gene expression occurred in hypothalamic cultures only, whereas ProOT mRNAs
      were undetectable. By contrast, prodynorphin and proenkephalin mRNAs could be
      detected in both hypothalamic and extrahypothalamic cultures, however, with a
      higher number of cells containing proenkephalin mRNAs. These observations
      demonstrated that AVP, dynorphin and enkephalin, but not OT genes, can be
      expressed in cultures prepared from embryonic rat brain as young as 16 days old.
      This is the first report of an early expression of opioid peptide genes within
      the central nervous system suggesting that opioids could be involved in the early
      phases of nervous system development.

PMID- 1980643
TI  - The actions of tulobuterol on isolated preparations of gravid human myometrium.
AB  - 1. The effects of tulobuterol (Abbott 54173) on the contractile force developed
      by electrically stimulated strips of gravid (gestation 36-40 weeks) human uterine
      muscle were compared with those of isoprenaline and adrenalin. 2. Isoprenaline
      produced inhibition of electrically evoked contractions of myometrium from 12 of
      17 women at concentrations at or below 1 mumol/L (range 0.001-1 mumol/L). It
      enhanced contractions at concentrations of 10-50 mumol/L. In tissues from the
      remaining five women isoprenaline produced neither inhibitory nor excitatory
      effects. Adrenalin (0.1-50 mumol/L) was found to enhance contractile force in a
      concentration-dependent manner (EC50 = 0.30 mumol/L). 3. In the presence of
      metoprolol (0.3 mumol/L), a selective antagonist at beta 1-adrenoceptors, the
      isoprenaline concentration-response relationship was shifted to the left,
      indicating that beta 1-adrenoceptors are present and that they mediate excitation
      in the human uterus. 4. In contrast tulobuterol (in neither the presence nor
      absence of metoprolol), in the same concentration range as isoprenaline and
      adrenalin, (0.001-50 mumol/L) was found to have no effect on the electrically
      evoked contraction of gravid human uterine muscle strips.

PMID- 1980645
TI  - Epilepsy and education: cognitive functions in learning behavior. A symposium.
      New Delhi, India, October 1989.

PMID- 1980644
TI  - [Studies on enzyme activities relating to amino acid mobilization in biopsied
      muscles].
AB  - We evaluated glutamine synthetase (GS) and alanine aminotransferase (GPT)
      activities in biopsied muscle from 40 cases of various neuromuscular diseases. GS
      and GPT catalyze the synthesis of glutamine and alanine, respectively, from amino
      acids derived in part from the breakdown of muscle proteins. The subjects were 7
      cases of muscular dystrophy; 1 Duchenne type (DMD), 3 limb-girdle type, 2
      facioscapulohumeral type (FSH), 1 Fukuyama type (FCMD); and 1 myotonic dystrophy
      (MyD); 5 mitochondrial myopathies; 11 inflammatory myopathies including 6
      polymyositis and 3 myopathy associated with collagen disease; 5 endocrinological
      myopathies including 2 periodic paralysis; and, 11 cases of neurogenic
      amyotrophies [4 amyotrophic lateral sclerosis (ALS), 4 spinal progressive
      muscular atrophy (SPMA) and 3 other types]. Control subjects were 8 patients with
      thigh operations. Biopsied muscle was homogenized and assayed for GS activity by
      the method of Smith et al.; GPT was assayed by commercial kit. Protein was
      assayed by the method of Lowry et al. Enzyme activities between mean -2SD and
      mean +2SD of controls were considered to be the normal range. GS activity in
      control subjects was 28.22 +/- 7.13 (mean +/- SD) nmol glutamine formed/mg
      protein/hr. Fifteen of 40 cases showed increased enzyme activity, including DMD
      and FCMD, the acute phase of polymyositis, and periodic paralysis. GPT activity
      in controls was 16.56 +/- 4.05 IU/mg protein. Sixteen of 40 patients showed
      increased enzyme activity: FCMD, FSH, MyD, inflammatory and endocrinological
      myopathy, and ALS. On the other hand, mitochondrial myopathy showed significantly
      decreased activity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1980646
TI  - On concanavalin A-treated striatal neurons quisqualate clearly behaves as a
      partial agonist of a receptor fully activated by kainate.
AB  - In cultured striatal neurons, maximal [3H]GABA release stimulated by quisqualate
      (QA) or alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) was 10-20
      times smaller than that stimulated by kainate (KA), and we have previously
      reported that QA or AMPA competitively inhibited KA-evoked GABA release. Since
      the lectin concanavalin A (Con A) has been shown to inhibit QA receptor
      desensitization, the interaction between QA and KA was further studied in Con A
      treated neurons. Con A dose-dependently and specifically potentiated QA- or AMPA
      evoked [3H]GABA release, so that maximal responses of QA or AMPA were half of
      that of KA. The responses of these agonists were inhibited by 6-cyano-7
      nitroquinoxaline-2,3-dione (CNQX) with similar apparent Ki values, indicating
      that they resulted from non-NMDA receptor activation. In Con A-treated neurons,
      QA and AMPA competitively inhibited the KA-induced GABA release. The apparent
      affinities of QA and AMPA in inhibiting the KA response were identical to their
      affinities in stimulating GABA release. Moreover, the maximal KA response
      measured in the presence of QA or AMPA was identical to that measured with KA
      alone. These results clearly indicate that to stimulate GABA release from Con A
      treated striatal neurons, QA and AMPA behave as partial agonists of a receptor
      fully activated by KA. These results further support the hypothesis that QA, AMPA
      and KA act on a common receptor type in striatal neurons.

PMID- 1980647
TI  - Characterization of Ca2(+)-mobilizing excitatory amino acid receptors in cultured
      chick cortical cells.
AB  - The effects of glutamate and other more selective excitatory amino acid (EAA)
      analogs on intracellular free calcium concentration ( [Ca2+]i) were examined in
      Fura 2-loaded cultured chick embryo cortical cells (90% neuronal). Four EAA
      receptors were evident in these studies: an N-methyl-D-aspartate (NMDA) receptor,
      a kainate receptor, and two quisqualate receptors. The [Ca2+]i response to NMDA
      was blocked or reversed by selective antagonists such as 2-amino-5
      phosphonovalerate (APV), MK801 and ketamine, as well as by desmethylimipramine
      and dextromethorphan. Glycine potentiated the [Ca2+]i response to NMDA, and high
      concentrations of glycine selectively overcame blockade by kynurenic acid, 6
      cyano-7-nitroquinoxaline-2,3-dione (CNQX), and cis-piperidine-2,3-dicarboxylic
      acid (PDA). The [(Ca2+]i response to kainate was generally larger than the NMDA
      response, and the kainate response desensitized slightly over the first minute.
      CNQX was more potent as an antagonist of the kainate response than of the NMDA
      response, even in the absence of added glycine; kynurenic acid and PDA conversely
      had little effect on the kainate response in these cells at concentrations which
      blocked the NMDA response. The desensitization of the [Ca2+]i response to kainate
      was greatly augmented by quisqualate and by the putative ionotropic quisqualate
      receptor agonist alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA).
      In the absence of kainate, both quisqualate and AMPA increased [Ca2+]i though
      less so than did NMDA or kainate. Quisqualate (and AMPA and glutamate) were not
      acting as partial agonists at the kainate receptor, since the potency of these
      agonists in reversing the kainate [Ca2+]i response was independent of kainate
      concentration. Quisqualate, but not AMPA, also produced a small increase in
      [Ca2+]i which preceded the negative effect of this agonist on the kainate
      response. This increase in [Ca2+]i could also be evoked by quisqualate or
      glutamate after inhibition of the kainate response by AMPA. Quisqualate and
      glutamate, but not the other EAA agonists, also increased [Ca2+]i after chelation
      of extracellular calcium with EGTA. This effect appears to be mediated by the
      metabotropic quisqualate receptor. These cells should provide a useful system for
      studying regulation and interactions of EAA receptors, and for screening drugs
      which might act at these receptors.

PMID- 1980648
TI  - Structural requirements of ATP for activation of basal and atrial natriuretic
      factor-stimulated guanylate cyclase in rat lung membranes.
AB  - ATP has been reported to increase basal and atrial natriuretic factor (ANF)
      stimulated guanylate cyclase activity. The structural features of ATP involved in
      the activation of guanylate cyclase were examined by employing a variety of ATP
      analogs with modification either at the phosphate chain or at the ribose moiety.
      Among the natural adenine nucleotides, ATP and ADP were able to increase both
      basal and ANF-stimulated guanylate cyclase activities in rat lung membranes. AMP
      had no effect. ATP was more effective than AMPPCP (the non-hydrolyzable analog of
      ATP), and ADP was more effective than ADP beta S and AMPCP (the hydrolysis
      resistant analogs of ADP) to increase basal and ANF-stimulated guanylate cyclase
      activities. Removal of the oxygen atom from the ribose moiety of ATP or ADP
      significantly reduced their potency. Thus, the length of the phosphate chain and
      the hydroxyl groups at the ribose moiety are both determinants for nucleotide
      mediated guanylate cyclase activation.

PMID- 1980649
TI  - Kinetic characterization of atrial natriuretic factor-sensitive particulate
      guanylate cyclase.
AB  - The present investigation describes kinetic characteristics of membrane-bound and
      Triton X-100-solubilized atrial natriuretic factor (ANF)-sensitive guanylate
      cyclase from bovine adrenal cortex. The kinetic analysis of both enzyme forms
      suggests that in the presence of manganese, ANF induces or stabilizes at least
      two apparent GTP*Mn2(+)- and in addition two Mn2(+)-binding sites. Addition of
      the natriuretic drug amiloride favors this state. ATP increases the vmax in the
      presence of ANF for GTP*Mg2+, but not for GTP*Mn2+ as a substrate. With GTP*Mg2+,
      amiloride has no effect on basal or ANF-stimulated activity, but slightly reduces
      the effect of ATP. Under all conditions tested, the enzyme follows regular
      Michaelis-Menten kinetics in the presence of Mg2+ and exhibits positive
      cooperativity with Mn2+. Positive cooperativity is also retained after Triton
      extraction. The results indicate that Triton extraction has no major influence on
      the kinetic properties of particulate guanylate cyclase when the extraction
      procedure is done carefully. The data also support the suggestion that multiple
      interactions of subunits might occur upon activation of the enzyme by ANF in the
      presence of Mn2+.

PMID- 1980650
TI  - Residues of some veterinary drugs in animals and foods. Joint FAO/WHO Expert
      Committee on Food Additives.

PMID- 1980652
TI  - [News and important progress in the fight against AIDS at the 6th International
      Conference in San Francisco].

PMID- 1980651
TI  - Specifications for identity and purity of certain food additives. Joint FAO/WHO
      Expert Committee on Food Additives.

PMID- 1980653
TI  - [Strong inhibition of gastric acid secretion: when is it justifiable?].

PMID- 1980654
TI  - A multi-center double-blind controlled trial of ursodeoxycholic acid for primary
      biliary cirrhosis.
AB  - A multi-center double-blind controlled trial of ursodeoxycholic acid (UDCA) for
      treatment of primary biliary cirrhosis (PBC) was carried out. Twenty two and 23
      patients were treated with 600 mg/day UDCA and placebo, respectively, for 24
      weeks. In UDCA-treated patients, fall of serum aspartate aminotransferase,
      alanine aminotransferase, alkaline phosphatase and gamma-glutamyltranspeptidase
      activities started within 4 weeks after start of the trial and continued
      throughout the trial period. The serum IgM level fell in 7 UDCA-treated patients
      examined but not in 10 placebo-treated patients examined. Serum bilirubin
      concentration showed no significant change at the end of the study in either of
      UDCA- and placebo-treated group of patients. There was no significant difference
      between these two groups with respect to the frequency of improvement of
      pruritus. In UDCA-treated patients, serum bile acid composition changed markedly,
      though its concentration showed no significant change. The percentage of total
      bile acid which ursodeoxycholic acid took up increased, whereas those which
      cholic acid, chenodeoxycholic acid and deoxycholic acid took up were decreased.

PMID- 1980655
TI  - Regulation of noradrenaline release in human cerebral arteries via presynaptic
      alpha 2-adrenoceptors.
AB  - 1. Electrical stimulation induced tritium release from branches of human middle
      cerebral arteries preincubated with [3H]noradrenaline (NA), which was reduced by
      the alpha 2-adrenoceptor agonists, clonidine and B-HT 920, and not affected by
      the alpha 1-agonist, methoxamine. 2. The stimulated tritium release was inhibited
      by yohimbine (alpha 2-antagonist), and increased by phentolamine (alpha
      antagonist) and prazosin (alpha 1-antagonist). 3. The inhibitory effect of
      clonidine was antagonized by yohimbine. 4. NA uptake was markedly reduced when
      the interval between the death and the autopsy was greater than 5 hr. 5. These
      data indicates the existence of presynaptic inhibitory alpha 2-adrenoceptors, but
      not alpha 1, in human cerebral arteries, and that the adrenergic nerve endings
      start to degenerate from 5 hr after death.

PMID- 1980656
TI  - Deadenylation of maternal mRNAs during Xenopus oocyte maturation does not require
      specific cis-sequences: a default mechanism for translational control.
AB  - The meiotic maturation of Xenopus oocytes initiates significant changes in the
      translation of a number of maternal mRNAs that coincide with alterations in their
      polyadenylation states. A considerable number of maternal mRNAs are deadenylated
      in mature oocytes, thereby reducing their translational efficiencies. In this
      report we demonstrate that deadenylation does not require specific cis-acting
      sequences. Polyadenylated RNAs derived from either ribosomal protein or beta
      globin mRNAs, or that contain non-mRNA-derived sequences, are deadenylated in
      mature oocytes. Translation of a substrate RNA is not required for its
      deadenylation. G10 mRNA is representative of a class of mRNAs that is
      translationally activated at maturation and contains the cytoplasmic
      polyadenylation element (U)6AU. A deletion mutant G10 transcript that lacks the
      (U)6AU element is not polyadenylated in mature oocytes but is deadenylated
      instead. Insertion of the (U)6AU element into the 3'-untranslated region of the
      ribosomal protein L1 mRNA is sufficient to prevent both its deadenylation and
      polysomal release in mature oocytes. These results indicate that the
      deadenylation and translational inactivation of maternal mRNAs during Xenopus
      oocyte maturation occur by a default pathway in which transcripts lacking a
      cytoplasmic polyadenylation element undergo poly(A) removal.

PMID- 1980657
TI  - Poly(A) removal during oocyte maturation: a default reaction selectively
      prevented by specific sequences in the 3' UTR of certain maternal mRNAs.
AB  - Certain maternal mRNAs lose their poly(A) tails during early development and
      concomitantly become translationally inactive. In this report we analyze the
      mechanism of poly(A) removal during frog oocyte maturation by injecting short
      synthetic RNAs. We demonstrate that removal of poly(A) during oocyte maturation
      is a default reaction: In the absence of any specific sequence information,
      poly(A) is removed. However, poly(A) removal can be prevented by specific
      sequences in the 3'-untranslated regions of certain maternal mRNAs. These
      sequences are also required for poly(A) addition during oocyte maturation and
      include AAUAAA and a nearby U-rich element. Mutations in either AAUAAA or the U
      rich element cause loss of poly(A) and not merely a failure to extend the poly(A)
      tail. We infer that poly(A) addition is required to escape poly(A) loss. The
      enzyme that removes the poly(A) during oocyte maturation appears to be a 3'----5'
      nuclease that prefers a 3'-terminal poly(A) segment. We discuss possible
      mechanisms by which poly(A) addition might circumvent default poly(A) removal and
      consider whether poly(A) removal is also a default reaction in somatic cells.
      Finally, we consider the possible implications of our results for the selectivity
      of poly(A) addition and removal, and for translational regulation during early
      development.

PMID- 1980658
TI  - Interactions of the Oct-1 POU subdomains with specific DNA sequences and with the
      HSV alpha-trans-activator protein.
AB  - Trans-activation by the herpes simplex virus (HSV) protein, alpha TIF (VP16), is
      dependent on an inducible enhancer sequence that contains a homolog of the
      octamer element. An ordered series of multiprotein complexes can be assembled on
      this enhancer, requiring the interactions of Oct-1, alpha TIF, and two additional
      cellular factors (C1 and C2). Oct-1 binds to the octamer homolog, whereas alpha
      TIF, also a sequence-specific DNA-binding protein, recognizes sequences within
      the HSV enhancer core. The partially purified C1 factor interacts directly with
      alpha TIF in the absence of DNA and is required to form a stabile Oct-1/alpha
      TIF/C1 factor complex. The POU domain of Oct-1 is a bipartite sequence
      recognition structure, as both the POU-specific box and the POU homeo box
      contribute directly to the recognition of the octamer element. Surprisingly, the
      POU homeo box alone is sufficient to direct the cooperative binding of alpha TIF
      and to assemble the Oct-1/alpha TIF/C1 factor complex.

PMID- 1980659
TI  - [Central neurotransmitters and regulation of gastric acid secretion].
AB  - Central neurotransmitter and/or neuromodulator candidates reported to affect
      gastric acid secretion are: (excitatory) acetylcholine, thyrotropin releasing
      hormone, GABA, oxytocin; (inhibitory) noradrenaline, adenosine, bombesin,
      calcitonin-gene related peptide, corticotropin releasing factor, beta-endorphin,
      neurotensin, neuropeptide Y, insulin-like growth factor II and prostaglandins.
      Regulation of gastric acid secretion by central administration of these
      substances in experimental animals such as rats and dogs are briefly reviewed,
      and central inhibitory mechanisms of this function are discussed based on our
      studies with noradrenaline and bombesin. Roles of hypothalamic nuclei such as the
      ventromedial nucleus and the lateral hypothalamus in regulation of autonomic
      nerve activities are also described as an introductory note.

PMID- 1980660
TI  - [Effectiveness of various combination therapies in patients with coronary heart
      disease].
AB  - There is only a limited number of studies available comparing the effectiveness
      of various combinations of anti-ischemic and antianginal substances in the same
      patients with coronary artery disease and stable angina pectoris and even these
      are restricted to either only a few drugs or a single point in time for testing.
      Accordingly, this study was undertaken to determine to what extent the
      combination of two or three drugs with different anti-ischemic mechanisms of
      action such as the long-acting form of the beta-blocker metoprolol and isosorbide
      dinitrate (ISDN) in sustained-release form as well as the calcium channel
      blockers nisoldipine and diltiazem in sustained-release form, which previously
      have not been tested in combination, are capable of enhancing effectiveness and
      prolonging duration of action. In a double-blind, randomized, crossover study in
      eleven patients with documented coronary artery disease and stable angina
      pectoris the effects of monotherapy with 200 mg metoprolol in long-acting form
      were compared with those of combined treatment with 120 mg ISDN sustained-release
      or 10 mg nisoldipine or 120 mg diltiazem sustained-release as well as ISDN and
      nisoldipine and finally, ISDN and diltiazem by means of an intraindividual
      analysis. For assessment of anti-ischemic and antianginal effects, symptom
      limited exercise testing was carried out before as well as three, eight, twelve
      and 24 hours after medication. The parameters analyzed were ST-segment depression
      at the highest comparable workload, ischemia-free and symptom-free exercise
      capacity (one minute prior to ST-segment depression of 1 mm or onset of angina
      pectoris) as well as the systolic blood pressure--heart rate product at the
      highest comparable workload and at the highest ischemia-free workload, that is
      one minute prior to an ischemic reaction of 1 mm. Based on the ST-segment
      depression, all combinations of two drugs (metoprolol and ISDN at three hours;
      metoprolol and diltiazem at eight hours) led to a significant or at least
      relative increase of effectiveness. On comparison of the various double
      combinations, those with nisoldipine showed an early dissipation of action which,
      twelve hours after administration, was significantly less marked than those with
      diltiazem. Of the two tested triple combinations, metoprolol, ISDN and diltiazem
      was either significantly more effective than the various double combinations
      (metoprolol and ISDN or metoprolol and nisoldipine, both at eight and twelve
      hours; metoprolol and diltiazem, twelve hours) or relatively more effective and
      showed clear prolongation of the effects in excess of twelve hours.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 1980661
TI  - Chromosomal analysis in Japanese couples with repeated spontaneous abortions.
AB  - Balanced chromosome rearrangements have been found at an increased frequency in
      couples with pregnancy wastage, especially recurrent spontaneous abortions,
      compared with the general population. In the present study, chromosomal analysis
      of peripheral blood cells, as one of the routine examinations of patients with
      repeated reproductive wastage, was performed on both partners of 639 Japanese
      couples. Among the 639 couples, 32 major chromosomal anomalies (5.0%) and 23
      minor chromosomal variants (3.6%) were found. Both partners of one couple had an
      abnormal karyotype. The 32 major anomalies consisted of 19 reciprocal
      translocations, 9 Robertsonian translocations, one large inversion, two triple-X
      females, and one Turner mosaicism. The 23 minor variants included 15 cases of
      pericentric inversion of chromosome 9. The total number of pregnancies in the 54
      couples with chromosomal anomalies was 181, but they resulted in only 18 normal
      liveborn neonates, indicating a 90.1% abortion rate. The present statistical
      study indicates that major chromosomal anomalies seem to be involved in repeated
      reproductive wastage.

PMID- 1980662
TI  - Comparison between laparotomy and operative laparoscopy in the treatment of
      moderate and severe stages of endometriosis.
AB  - A retrospective study was designed to compare the results of treatment of
      moderate and severe stages of endometriosis by laparotomy and by laparoscopy.
      Patients were divided into three groups: the first consisted of 42 patients
      treated by laparotomy followed immediately with danazol treatment for 6-9 months;
      the second, 44 patients treated by operative laparoscopy followed immediately
      with danazol treatment for 4-6 months; and the third, 62 patients treated by
      operative laparoscopy followed immediately with danazol treatment for 6-10 weeks.
      The cumulative pregnancy rate in the laparoscopy groups was better than that of
      the laparotomy group. Most patients who failed to conceive underwent a second
      look laparoscopy for reevaluation. Residual endometriosis and associated
      adhesions were noticed least in the third group. It is concluded that operative
      laparoscopy could be efficiently used for the treatment of moderate or even
      severe endometriosis.

PMID- 1980663
TI  - Abdominal pregnancy as a result of gamete intrafallopian transfer (GIFT) and
      subsequent treatment with methotrexate: case report.
AB  - A patient underwent a minilaparotomy for gamete intrafallopian transfer (GIFT),
      and subsequently developed an abdominal pregnancy. The patient was treated with
      methotrexate, and a good resolution was obtained, with total disappearance of
      beta-hCG titers after 22 days from the beginning of therapy.

PMID- 1980664
TI  - Changes in American A.I.D. practice during the past decade.
AB  - We conducted a survey of donor artificial insemination (AID) practices within the
      United States. The survey document was sent to 360 practitioners listed by
      national infertility organizations as performing AID. In addition, we queried 100
      practices that had responded to a similar survey in 1978. AID was actually
      performed during the survey year by 167 of the 282 respondents. Relatively few
      practices (23%) inseminated more than 10 patients per month. Donor payments
      increased from a mean of $25 to $40 over that period. A significant increase in
      the use of frozen semen was found. A majority of practices (52%) used a
      combination of basal body temperature and urinary LH to time inseminations. The
      fraction of practitioners who inseminated unmarried women increased substantially
      since the previous survey. The maximum number of pregnancies resulting from a
      single donor has not changed over the decade. However, on the average, a single
      donor is fathering fewer children. The percentage (39%) of practices that
      inseminate women because of genetic disease in the husband's family has remained
      about the same. Records of donors and AID children were maintained by 40% of the
      respondents, representing no change from the previous survey. Our data suggest
      that as many as 23,400 infants may have resulted from AID conceptions during the
      survey year. Further changes in the practice of AID can be expected as a result
      of the 1988 federal recommendations that all donor inseminations be undertaken
      with cryopreserved, quarantined semen.

PMID- 1980665
TI  - Artificial insemination with fresh donor semen.
AB  - One hundred and thirty-four patients received artificial insemination with fresh
      donor semen (AID). Using the life-table method of analysis, 72 pregnancies
      occurred, yielding a crude conception rate of 53.7%. The 134 women received an
      average of three inseminations per cycle for a total of 1,282 inseminations near
      the day of ovulation. The majority of pregnancies occurred by the seventh cycle.
      Forty-two pregnancies were achieved using a single donor; 30 pregnancies required
      changing the donor once, twice, or more. Among 42 patients who subsequently were
      treated with clomiphene citrate, 16 conceived. Two of these patients became
      pregnant after receiving hMG and hCG additionally. The life-table analysis of
      cumulative pregnancy rates following infertility therapy provides a relatively
      simple, powerful, and reliable tool for evaluating the effectiveness of therapy
      and its benefits. Patients should be advised that their chances of conception
      with AID approach that of normal fertile couples, provided that these patients
      persist in their treatment.

PMID- 1980666
TI  - Endometriosis-associated infertility: evaluation of preoperative use of danazol,
      gestrinone, and buserelin.
AB  - In order to assess adequately the effectiveness of danazol, Gestrinone, and
      Buserelin, a prospective nonrandomized study was initiated in 126 patients with
      laparoscopically confirmed ovarian endometriosis. After hormonal therapy,
      laparotomy with microsurgical resection of endometriotic cysts was carried out.
      Regression (greater than 25%) of ovarian endometriosis was noted in 30%, 34%, and
      73% of cases after danazol, Gestrinone, and Buserelin, respectively. The
      pregnancy rate in moderate endometriosis (53%) differed significantly from the
      rate obtained in severe endometriosis (45%). The highest percentages were found
      after Buserelin therapy. In conclusion, Buserelin emerged superior to danazol or
      Gestrinone treatment. Nevertheless, hormonal treatment leads to an incomplete
      suppression of ovarian endometriotic implants and this suggests the necessity of
      surgically removing invasive ovarian endometriosis.

PMID- 1980667
TI  - Stability and purity profile of gonadorelin acetate: a high-purity gonadotropin
      releasing hormone.
AB  - Recently, several reports of adverse reactions after pulsatile GnRH (gonadorelin
      hydrochloride) infusion therapy have appeared in the medical literature. Although
      the cause of these reactions has been associated with GnRH itself, the
      contributions of impurities and degradation products in the administered drug
      have not been determined, suggesting that the use of high-purity material may be
      advantageous in controlling unwanted side effects. This study evaluates the
      purity and long-term stability of a new GnRH product, gonadorelin acetate
      (Lutrepulse, Ortho Pharmaceutical Corporation). Both the purity and potency of
      the drug substance, the lyophilized product for injection, and the reconstituted
      material that would be transferred to the infusion pump system were monitored
      using high-performance liquid chromatography. The gonadorelin acetate drug
      substance was found to be stable for at least 12 months when stored at 24 degrees
      C in 50% relative humidity, and showed no degradation even under accelerated
      storage conditions. Similarly, the lyophilized product also showed excellent
      stability for at least 18 months when stored at 24 degrees C in 50% relative
      humidity. Upon reconstitution, gonadorelin acetate was found to be stable for at
      least 45 days when stored at 24 degrees C or 37 degrees C.

PMID- 1980668
TI  - The effect of intrauterine insemination on uterine activity.
AB  - Intrauterine insemination (IUI) may lead to very painful uterine cramps, which
      are due to the effect of the prostaglandin (PG) content of human semen. The
      purpose of this study is to present the reactivity of the human uterus to the
      placement of raw semen in the intrauterine space and to evaluate the related
      response patterns. A statistically significant uterine activity change was
      observed between the periods before and after intrauterine insemination. Three
      minutes after IUI, an increase in uterine activity was observed; it became most
      prominent at five to ten minutes. This stimulation was sustained for 30 minutes
      and decreased gradually. Although there is an increase in uterine activity
      following intrauterine insemination, neither pelvic pain nor abdominal discomfort
      was reported. According to this observation, we suggest that a semen volume of 1
      mL might be used safely for intrauterine insemination.

PMID- 1980669
TI  - Inhibition of postsurgical adhesions by liposomes containing nonsteroidal
      antiinflammatory drugs.
AB  - Intraperitoneal administration of liposomes containing the nonsteroidal
      antiinflammatory drugs (NSAID) ibuprofen or tolmetin was tested for their
      efficacy in the prevention of adhesion formation. Both NSAIDs were able to reduce
      adhesions in an animal model for moderate adhesion formation. However, tolmetin
      containing liposomes were more efficacious than ibuprofen-containing liposomes in
      the reduction of adhesion formation following bilateral uterine abrasion and
      devascularization surgery.

PMID- 1980670
TI  - Effect of somatostatin analogs on gastric acid secretion in dogs and rats.
AB  - The effects of several superactive analogs of somatostatin on gastric acid
      response to various exogenous and endogenous stimulants were investigated in
      conscious dogs and rats with gastric fistulae (GF). The inhibition was compared
      to that induced by somatostatin-14 (S-S-14) at two dose levels. Several
      octapeptide analogs of somatostatin including D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp
      NH2 (RC-160) and D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2 (RC-121), which were
      superactive in tests on suppression of GH levels, were 4-5 times more potent than
      S-S-14 in inhibiting desglugastrin-stimulated gastric acid secretion in GF dogs.
      The analog RC-160 also reduced the rise in serum gastrin levels and gastric acid
      secretion induced by sham feeding (SF) in dogs with gastric and esophageal
      fistulae (EF), but did not decrease food consumption. Gastric acid secretion
      induced by histamine (80 micrograms/kg/h) in dogs was not affected by 1-5
      micrograms/kg/h of analog RC-121 or by 5 micrograms/kg/h of S-S-14. Analogs RC
      160, RC-121, and RC-98-I (D-Trp-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-NH2) and others
      also powerfully inhibited desglugastrin-induced potent as S-S-14 in dogs but its
      activity was higher in rats. The results indicate that octapeptide analogs which
      are superactive in GH-inhibition tests are also more potent than S-S-14 in
      suppressing gastric acid secretion. These findings may be of clinical value.

PMID- 1980671
TI  - Evidence for presence of Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) in human brain cortex.
AB  - Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) was previously isolated from bovine hypothalamus.
      We have now purified it from the parietal cortex of human brain tissue by gel
      filtration chromatography and four subsequent high performance liquid
      chromatographic steps. During isolation, the peptide content was followed by
      radioimmunoassay and compared with the elution of synthetic Tyr-MIF-1 in
      identical chromatographic systems. This extends evidence for the presence of Tyr
      MIF-1 from bovine to human brain tissue and from hypothalamus to cortex.

PMID- 1980672
TI  - Studies on somatostatin with time-resolved spectroscopy and molecular dynamics
      simulations.
AB  - Somatostatin was studied by time-resolved fluorescence spectroscopy and by
      molecular dynamics simulations. The results obtained indicate the existence of
      mainly one conformation in DMSO, and the existence of several conformations in
      other solvents. Molecular dynamics simulations showed that the most important
      region for activity (residue 7-9) is also the most flexible region in the
      peptide.

PMID- 1980673
TI  - Distress, neuromodulation, and ontogeny. Papers presented at the international
      congress. Madonna di Campiglio, Italy, July 26-29, 1989. Proceedings.

PMID- 1980674
TI  - Beta-endorphin in peripheral mononuclear cells: physiological and pharmacological
      modifications.

PMID- 1980675
TI  - Does HIV cause AIDS? An updated response to Duesberg's theories.
AB  - AIDS is an acquired immunodeficiency syndrome caused by the lentivirus HIV and
      characterized by a successive depletion of CD4 helper/inductor lymphocytes. The
      humoral and cellular immune deficiency is the basis for the development of
      opportunistic infections and tumors. Because of a multitude of different
      bacterial, viral, and parasitic opportunistic agents, AIDS is typified by a
      number of divergent clinical symptoms. As with many lentiviruses, HIV is
      difficult to demonstrate in the organism, especially in asymptomatic carriers.
      Although the rate of infection in peripheral lymphocytes appears to be low, there
      is an increasing amount of virological and immunological data which help to
      explain the slow but irreversible failure of the immune defense. We still know
      relatively little about the pathogenic mechanisms of HIV, although a number of
      the presently available experimental results provide useful starting points for
      subsequent investigations. Peter H. Duesberg recently published that HIV and AIDS
      may well be correlated, but stated that HIV is not the cause of AIDS. Duesberg
      bases his hypothesis on the fact that HIV fulfills neither Koch's classic
      postulates nor several more of his own postulates for viral pathogenesis.
      Following the summary of individual pathogenic mechanisms of HIV infection, the
      separate points of Duesberg's hypothesis are discussed in detail. It is made very
      clear that the magnitude of epidemiologic, clinical, and experimental
      observations and results argue for a causal role of HIV and AIDS.

PMID- 1980676
TI  - U.S. v. Charters.

PMID- 1980677
TI  - Survival of both young and aged sympathetic neurons in the adrenal cortex after
      autotransplantation.
AB  - Sympathetic ganglion tissue of 3-months- and 18-months-old Fischer-344 rats was
      autotransplanted into the adrenal gland in order to determine the effect of aging
      on the survival of grafted neurons. Adrenal cortex was chosen as the host tissue
      because it is well vascularized and has a high concentration of glucocorticoids,
      which stimulate the synthesis of catecholamines. At 4 weeks following the
      transplantation, the density of neurons was decreased in all transplants, but
      approximately the same proportion of remaining neurons showed tyrosine
      hydroxylase immunoreactivity as in intact ganglia. At 8 weeks, a subpopulation of
      large neurons showed an increased accumulation of age pigment. The heavily
      pigmented neurons were usually devoid of catecholamines, whereas small non
      pigmented neurons frequently showed strong catecholamine histofluorescence and
      tyrosine hydroxylase immunoreactivity. There was no marked difference between old
      and young animals in the survival of transplanted neurons. The results show that
      the sympathetic neurons from both 3-months-and 18-months-old animals survived the
      autotransplantation procedure. The humoral environment of the adrenal cortex may
      be beneficial for the restoration of the integrity of sympathetic neurons.

PMID- 1980678
TI  - Distribution and ontogeny of chromogranin A and tyrosine hydroxylase in the
      carotid body and glomus cells located in the wall of the common carotid artery
      and its branches in the chicken.
AB  - Development and distribution of chromogranin A and tyrosine hydroxylase in the
      carotid body and glomus cells located in and around arteries were examined in
      chickens at various developmental stages by an immunohistochemical staining. In 9
      day-old embryos, numerous cells immunoreactive for tyrosine hydroxylase were
      already detected in the connective tissue surrounding the carotid body. Some of
      these cells also showed immunoreactivity for chromogranin A. At 10 days of
      incubation, a few cells immunoreactive for tyrosine hydroxylase and chromogranin
      A were detected within the carotid body parenchyma. At 12 days of incubation,
      almost all glomus cells of the carotid body were intensely immunoreactive for
      these substances. Furthermore, numerous tyrosine hydroxylase- and chromogranin A
      immunoreactive cells were observed in the wall of the common carotid artery,
      along the whole length of the carotid body artery, and around the roots of the
      inferior thyroid artery, the ascending esophageal artery and the
      esophagotracheobronchial artery; the cells already exhibited adult pattern of
      distribution at this stage of development. Thereafter, glomus cells
      immunoreactive for both substances gradually increased in number and in intensity
      of immunoreactivity with age, although the cells located in the wall of the
      common carotid artery lost immunoreactivity for tyrosine hydroxylase after
      hatching.

PMID- 1980679
TI  - Predominant periportal expression of the phosphoenolpyruvate carboxykinase and
      tyrosine aminotransferase genes in rat liver. Dynamics during the daily feeding
      rhythm and starvation-refeeding cycle demonstrated by in situ hybridization.
AB  - The zonal distribution of phosphoenolpyruvate carboxykinase (PCK) and tyrosine
      aminotransferase (TAT) mRNA in liver was studied by in situ hybridization with
      radiolabelled cRNA probes and the abundance of PCK and TAT mRNA was quantified by
      Northern blot analysis of total RNA with biotinylated cRNA probes. Livers were
      taken from rats during a normal 12 h day/night rhythm, when they had access to
      food only during the dark period from 7 pm to 7 am, or during refeeding, when
      they had access to food after having been starved for 60 h. 1. Daily feeding
      rhythm: High levels of PCK mRNA were distributed mainly in the periportal and
      intermediate zone during the fasting period at noon and 6 pm. Feeding caused a
      rapid decrease in PCK mRNA level and a restriction of PCK mRNA localization to
      the periportal area within the first 2 h. No further alterations were observed
      during the following hours of the feeding period. TAT mRNA was distributed also
      in the periportal and intermediate zone during the fasting period. Feeding first
      reduced the mRNA level without changing the distribution pattern. Then towards
      the end of the feeding period TAT mRNA increased again to half-maximal levels and
      became restricted mainly to the periportal area. 2. Starvation-refeeding cycle:
      High amounts of PCK mRNA as well as of TAT mRNA were localized predominantly in
      the periportal and intermediate zone after 60 h of starvation. PCK and TAT mRNA
      both decreased markedly during the first 2 h of refeeding and then remained
      almost constant.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1980680
TI  - Comparative analysis of human cytomegalovirus a-sequence in multiple clinical
      isolates by using polymerase chain reaction and restriction fragment length
      polymorphism assays.
AB  - The human cytomegalovirus (HCMV) a-sequence (a-seq) is located in the joining
      region between the long (L) and short (S) unique sequences of the virus (L-S
      junction), and this hypervariable junction has been used to differentiate HCMV
      strains. The purpose of this study was to investigate whether there are
      differences among strains of human cytomegalovirus which could be characterized
      by polymerase chain reaction (PCR) amplification of the a-seq of HCMV DNA and to
      compare a PCR method of strain differentiation with conventional restriction
      fragment length polymorphism (RFLP) methodology by using HCMV junction probes.
      Laboratory strains of HCMV and viral isolates from individuals with HCMV
      infection were characterized by using both RFLPs and PCR. The PCR assay amplified
      regions in the major immediate-early gene (IE-1), the 64/65-kDa matrix
      phosphoprotein (pp65), and the a-seq of the L-S junction region. HCMV laboratory
      strains Towne, AD169, and Davis were distinguishable, in terms of size of the
      amplified product, when analyzed by PCR with primers specific for the a-seq but
      were indistinguishable by using PCR targeted to IE-1 and pp65 sequences. When
      this technique was applied to a characterization of isolates from individuals
      with HCMV infection, selected isolates could be readily distinguished. In
      addition, when the a-seq PCR product was analyzed with restriction enzyme
      digestion for the presence of specific sequences, these DNA differences were
      confirmed. PCR analysis across the variable a-seq of HCMV demonstrated
      differences among strains which were confirmed by RFLP in 38 of 40 isolates
      analyzed. The most informative restriction enzyme sites in the a-seq for
      distinguishing HCMV isolates were those of MnlI and BssHII. This indicates that
      the a-seq of HCMV is heterogeneous among wild strains, and PCR of the a-seq of
      HCMV is a practical way to characterize differences in strains of HCMV.

PMID- 1980681
TI  - Laboratory investigation of Acanthamoeba keratitis.
AB  - Following the diagnosis of Acanthamoeba keratitis in a contact lens wearer, the
      antimicrobial susceptibility of the clinical isolate and the environmental source
      of the infection were investigated. Contrary to previous reports, in vitro
      antimicrobial testing showed that the infecting strain was inherently resistant
      to propamidine isethionate. Restriction endonuclease digestion analysis of
      Acanthamoeba whole-cell DNA of strains isolated from the patient's cornea,
      contact lens storage container, saline rinsing solution, and kitchen cold-water
      tap showed that the isolates were identical. This implicates, for the first time,
      domestic tap water as the source of Acanthamoeba sp. in this infection. It is
      therefore recommended that the use of homemade saline solutions and the rinsing
      of contact lenses in tap water be strongly discouraged.

PMID- 1980683
TI  - [Selection of therapeutic methods for unstable angina pectoris].

PMID- 1980682
TI  - Oligonucleotide probe for detection of the enteropathogenic Escherichia coli
      (EPEC) adherence factor of localized adherent EPEC.
AB  - The enteropathogenic Escherichia coli adherence factor (EAF) probe detects
      isolates of enteropathogenic E. coli that exhibit localized adherence to HEp-2
      cells. A 21-base oligonucleotide probe was constructed on the basis of a sequence
      from within the 1-kb EAF probe and was shown to have greater sensitivity and
      specificity than the EAF fragment probe in detecting localized adherent E. coli.

PMID- 1980684
TI  - [Drug therapy of unstable angina].

PMID- 1980685
TI  - Human apolipoprotein A-I gene promoter polymorphism: association with
      hyperalphalipoproteinemia.
AB  - An apolipoprotein A-I gene promoter polymorphism, due to an adenine (A) to
      guanine (G) transition 78 base pairs upstream from the transcription initiation
      site, was studied by amplification of the corresponding region of the apoA-I
      gene, DNA sequencing, and allele-specific oligonucleotide hybridization. The
      frequency of the polymorphism was studied on female and male individuals
      classified into three groups according to the high density lipoprotein (HDL)
      cholesterol concentration. The allelic frequencies for the A polymorphism were
      0.10, 0.14, 0.27 in women and 0.08, 0.17, 0.14 in men in the lowest, in the
      intermediate (between 10th and 90th percentile), and the highest decile of HDL
      cholesterol levels, respectively. Statistical analysis showed a significant
      difference of allelic frequencies between the highest and the lowest deciles (P
      less than 0.006) and between the highest and the intermediate deciles of HDL
      cholesterol in women (P less than 0.04) but not in men. As the sequences
      surrounding the polymorphism are known to be involved in transcription
      modulation, it is possible that the A-G transition polymorphism may have an
      influence on apoA-I synthesis and, in consequence, on the HDL cholesterol levels
      in women.

PMID- 1980686
TI  - Homologous and heterologous regulation of somatostatin-binding sites on chicken
      adenohypophysial membranes.
AB  - Binding of 125I-labelled [Tyr1]-somatostatin (125I-[Tyr1]-SRIF) to pituitary
      caudal lobe membranes was suppressed in immature chickens 1 and 2 h after i.v.
      administration of unlabelled SRIF at concentrations of 1-100 micrograms/kg. In
      vitro preincubation of chicken pituitary glands for 0.5-4.0 h with 0.1 mumol
      SRIF/l similarly reduced the binding of 125I-[Tyr1]-SRIF to caudal lobe membrane
      preparations. After a 4-h incubation in 0.1 mmol SRIF/l, the withdrawal of SRIF
      from the incubation media was accompanied 4 h later by a partial recovery in the
      binding of 125I-[Tyr1]-SRIF to pituitary membranes. Passive immunoneutralization
      of endogenous SRIF resulted in a prompt (within 1 h) and sustained (for at least
      24 h) suppression of 125I-[Tyr1]-SRIF binding to pituitary membranes. The i.m.
      administration of cysteamine (300 mg/kg) to 12-week-old birds depleted
      hypothalamic SRIF stores and decreased the density of 125I-[Tyr1]-SRIF-binding
      sites in the caudal and cephalic lobes of the chicken pituitary gland. The
      reduction in SRIF content and in SRIF-binding sites occurred within 1 h of
      cysteamine administration and was maintained for at least 24 h. In 6-week-old
      birds, cysteamine (300 mg/kg) administration suppressed pituitary binding of 125I
      [Tyr1]-SRIF for at least 5 days. Circulating concentrations of GH were markedly
      decreased 1 and 4 h after cysteamine injection, but not after 24 h.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1980687
TI  - Predictive value of cytomegalovirus viraemia for the occurrence of CMV organ
      involvement in AIDS.
AB  - In HIV-infected patients, the presence of cytomegalovirus (CMV) viraemia is
      predictive of the development of acquired immunodeficiency syndrome (AIDS), but
      it is not known whether it predicts further occurrence of CMV organ involvement.
      To assess the predictive value of CMV viraemia in the occurrence of CMV organ
      involvement, CMV blood cultures were performed at the onset of AIDS in 71
      patients. They were prospectively followed up for at least 6 months, with a mean
      of 16.6 +/- 7 months (6-36 months). CMV viraemia was present in 28/71 patients
      (39.5%) at the onset of AIDS. CMV organ involvement occurred in 18/71 patients
      (25.4%) after 8.7 +/- 3.3 months. Fourteen of the 28 patients (50%) with early
      CMV viraemia developed CMV organ involvement after 7.7 +/- 6.3 months as compared
      with 4/43 patients (9.3%) who were not viraemic at the onset of AIDS with a mean
      follow-up of 11.8 +/- 3.8 months (P less than 0.001). At the time of CMV organ
      involvement, CMV viraemia, however, was present in 94.4% of the cases. No
      differences in survival was observed between initially viraemic and non-viraemic
      patients. No difference has found in mean CD4 cell count between viraemic and non
      viraemic patients. This high predictive value of early CMV viraemia in AIDS for
      the occurrence of CMV organ involvement underlines the need for repeated search
      for CMV organ involvement when CMV viraemia is detected, and for less toxic
      antiviral drugs that might be used earlier.

PMID- 1980688
TI  - Benzodiazepines: therapeutic, biological, and psychosocial issues.

PMID- 1980689
TI  - Pharmacological mechanisms of benzodiazepine withdrawal.
AB  - The pharmacology of the benzodiazepine receptor is unusual in relation to other
      receptors in that there exist three types of ligand: agonists (e.g. diazepam),
      which are anxiolytic and anticonvulsant; antagonists (e.g. flumazenil), which are
      neutral; and inverse agonists (e.g. FG 7142), which are anxiogenic and
      proconvulsant. Chronic administration of agonists leads to tolerance and
      withdrawal, and produces a global shift in benzodiazepine receptor function with
      attenuation of agonist and enhancement of inverse agonist actions. These changes
      appear without alterations in receptor number or affinity, and may reflect a
      shift in efficacy, "withdrawal shift", at the receptor. Treatment with flumazenil
      during benzodiazepine agonist administration, or even in the period after the
      last dose, can prevent or reverse this efficacy shift as indicated by a lack of
      sensitization to inverse agonists. The clinical implications of these findings
      are discussed.

PMID- 1980690
TI  - Neuroendocrine effects of benzodiazepines.
AB  - Benzodiazepine administration has been associated with alterations in
      neuroendocrine function both in experimental animals and in humans. Clinical and
      laboratory data indicate that the beta-carbolines, a class of active
      benzodiazepine receptor inverse agonists, cause behavioral and neuroendocrine
      changes characteristic of anxiety and stress. In contrast, the "classic"
      benzodiazepine receptor agonists such as diazepam can reduce anxiety and inhibit
      stress-induced increases in anterior pituitary hormone secretion. Although the
      site of action and mechanisms by which benzodiazepines alter anterior pituitary
      hormone secretion are still under investigation, evidence suggests that the
      effects are mediated in the brain, primarily through actions at benzodiazepine
      receptors in the hypothalamus. The benzodiazepines may act at GABA-coupled
      benzodiazepine receptors in the hypothalamus or other regions of the brain to
      potentiate the effects of endogenous GABA. It also is believed that brain
      monoamines may modulate the effects of endogenous GABA. Brain monoamines have
      also been reported to modulate the effects of benzodiazepines on stress-induced
      hypothalamic-pituitary-adrenocortical function. Direct effects of the
      benzodiazepines on central- and peripheral-type benzodiazepine receptors in the
      anterior pituitary have also been documented.

PMID- 1980691
TI  - Benzodiazepines and alcohol.
AB  - The frequency and quantity of alcohol consumption is a major consideration in
      patients who need treatment with benzodiazepines. Alcohol affects the GABA
      benzodiazepine-chloride ionophore complex and has an agonist-like action. Thus,
      additive interactions should be expected from combining alcohol with
      benzodiazepines. Furthermore, alcohol has clinically meaningful anxiolytic
      efficacy, and many anxious patients may take advantage of that fact. Therefore,
      co-administration of alcohol and benzodiazepines is to be expected in an anxious
      patient receiving benzodiazepines who does not totally abstain from alcohol. This
      article reviews three clinically relevant issues concerning benzodiazepines and
      alcohol: (1) interactions of benzodiazepines with social drinking in patients
      taking benzodiazepines for indications unrelated to alcoholism; (2) use of
      benzodiazepines in treatment of alcohol withdrawal; and (3) use of
      benzodiazepines in patients with alcohol dependence.

PMID- 1980692
TI  - The benzodiazepines as drugs of abuse.
AB  - Benzodiazepines are rarely used as "party" or "good time" drugs. Recent studies
      of drug abuse liability have found that benzodiazepines are minor euphoriants:
      they are neither sought nor valued on the same level as cocaine, methaqualone, or
      even alcohol. Although they do have mild to moderate euphoriant effects in
      recreational drug users, detoxified chronic alcoholics and, at very high dosages,
      detoxified sedative "addicts", only a small proportion of patients entering drug
      abuse treatment programs cite benzodiazepine use as their primary drug problem.
      However, it is difficult to estimate the extent to which benzodiazepines are
      primary drugs of abuse, i.e. the extent of their ability to induce euphoria with
      psychic dependence and active drug-seeking behavior. This may be due in part to
      inconsistent or ambiguous reporting terminology and reliance on laboratory
      studies without comparisons with actual street use. In addition, it is unclear if
      patients admitted to emergency rooms for non-medical use of benzodiazepines are
      typical of all patients who abuse these drugs. This article will examine the
      current data available on benzodiazepine abuse and will assess the extent to
      which benzodiazepines are used as primary drugs of abuse.

PMID- 1980693
TI  - Benzodiazepine dependency discontinuation: focus on the chemical dependency
      detoxification setting and benzodiazepine-polydrug abuse.
AB  - Benzodiazepines are commonly encountered in both psychiatric and chemical
      dependency treatment settings. However, in the chemical dependency setting,
      benzodiazepines are most frequently used as secondary drugs of abuse, and are
      most often found within a polydrug use pattern. Benzodiazepine use by the drug
      abusing population consists of the combined use of benzodiazepines with other
      psychoactive drugs. They are used to medicate cocaine toxicity, as a secondary or
      tertiary drug to boost the effects of alcohol or heroin, and by those who have
      developed tolerance and dependence to sedative-hypnotic drugs. The presence of an
      anxiety disorder, a family history of addiction, or benzodiazepine polydrug use
      will significantly affect the type of withdrawal a patient will experience and
      its treatment course. Medical procedures accepted for benzodiazepine
      discontinuation include (1) graded reduction; (2) substitution of a long-acting
      benzodiazepine; and (3) phenobarbital substitution.

PMID- 1980694
TI  - Efficacy of benzodiazepines in panic disorder and agoraphobia.
AB  - Until recently, the benzodiazepines were believed to be ineffective in the
      treatment of panic disorder, with and without agoraphobic avoidance. Recent
      trials have shown, however, that panic disorder patients respond to
      benzodiazepines as well as to tricyclic antidepressants and monoamine oxidase
      (MAO) inhibitor antidepressants. Most of the controlled-trial investigations of
      benzodiazepines in panic disorder patients have evaluated the effects of
      alprazolam. However, early uncontrolled trials using other benzodiazepines have
      documented their effectiveness in panic disorder as well. This article reviews
      the evidence of the efficacy of alprazolam and other benzodiazepines in the
      treatment of panic disorder and their clinical use.

PMID- 1980695
TI  - Future directions in the treatment of anxiety.
AB  - Future directions for anxiety disorders may be split into three areas: research,
      clinical practice, and public attitudes. With regard to research, we must learn
      much more about the clinical course of anxiety disorders. Is it a short-term
      disease or a lifetime illness characterized by recurrence and chronicity? Our
      classification system must be refined and diagnostic criteria sharpened. Clinical
      practice issues are of greatest importance to the medical community and to our
      patients. We must increase our knowledge of what treatments to prescribe for what
      disorders, and develop approaches to discontinuation which are practicable. We
      must work in the public arena to foster the notion that anxiety disorders are
      diseases, and not expressions of character flaws. We must educate our colleagues
      in the mental health profession, our colleagues in the general health care
      community, and the general public at large.

PMID- 1980696
TI  - Benzodiazepines: therapeutic, biological and psychosocial issues. Symposium
      summary.
AB  - In approaching the end of this symposium discussed at this conference, we have
      examined a wealth of information on the appropriate use of benzodiazepines, and
      find ourselves paradoxically only at the beginning. The issues we have approached
      extend from molecules to society. Many questions remain unanswered; many issues
      remain unresolved. In essence, the future requires far more systematic studies
      than are yet in hand. Relative value must be assigned to the topics in an attempt
      to distinguish issues that truly are problematic from those that are nonissues.
      It is clear that as physicians, we want to be more informed in the management of
      complications of all beneficial medications, including benzodiazepine use. After
      all, balancing the risks and benefits of any therapeutic option in the treatment
      of human ailments is what the art and science of medicine are all about.
      Furthermore, if we are to counter the hysteria that can surround almost any form
      of medical therapy, we have a responsibility to educate patients, physicians, and
      the general public about the burden of psychiatric disorders, and the risks and
      benefits of treatment.

PMID- 1980697
TI  - Depression and panic anxiety: the effect of depressive co-morbidity on response
      to drug treatment of patients with panic disorder and agoraphobia.
AB  - Numerous studies have established that there is increased co-morbidity of
      depressive symptoms among patients with panic disorder with and without
      agoraphobia, but questions remain as to whether the symptom pattern and clinical
      course are similar to that of primary depressions. The Cross-National
      Collaborative Panic Study was initiated to study the effects of alprazolam, a
      triazolobenzodiazepine, in the treatment of panic disorder. In the first phase,
      which included more than 500 subjects, alprazolam was compared against placebo.
      In the second phase, alprazolam was compared with imipramine and placebo in a
      double-blind, randomized, controlled trial. Results of both the first and second
      phases will be reviewed as they bear on the issue of drug treatment of secondary
      depression accompanying panic disorder. The presence of depressive symptoms does
      not adversely influence anti-panic and anti-phobic response to medication.
      Equivalent drug-placebo differences occur on multiple measures of anxiety-
      including the number and intensity of panic attacks, phobias, anticipatory
      anxiety, and overall anxiety.

PMID- 1980698
TI  - Cardiovascular considerations in selection of anti-panic pharmacotherapy.
AB  - Patients with panic disorder may be at increased risk for cardiovascular
      morbidity and mortality. There is also preliminary evidence that some
      cardiovascular risk factors may be increased in patients with panic disorder.
      Since anti-panic medications can alter cardiovascular function, the
      cardiovascular effect of these medications should be considered, particularly
      when used in patients with cardiovascular disease. This article will review the
      cardiovascular side effects of anti-panic medications.

PMID- 1980700
TI  - The nosology of abuse and dependence.
AB  - Physicians who prescribe benzodiazepines often are asked by their patients if
      these drugs might be addicting or have potential for abuse. Clarifying these
      concepts is difficult because of numerous "gray areas" of drug use and confusion
      over medical criteria for such terms as "addiction", "dependence", and
      "tolerance". Many of the efforts to clarify the terminology regarding substance
      habituation, abuse, and addiction have resulted in additional confusion. They
      have resulted in overlapping definitions of abuse and dependence, the injection
      of moral judgments into scientific terms, and difficulty separating the diagnoses
      of the physical dependence (caused by prolonged use of a wide variety of drugs,
      many of which are never abused) from that of physical dependence secondary to an
      abusive pattern of use. This article will trace the history of the various
      definitions currently in use, and will suggest newer terminology to replace
      misleading or erroneous terms.

PMID- 1980699
TI  - Do benzodiazepines have a role in the prevention or treatment of coronary heart
      disease and other major medical disorders?
AB  - Increased coronary disease rates, as well as increased all-cause mortality, in
      persons with high levels of hostility/anger and in persons suffering from panic
      disorder or phobic anxiety suggest that biological concomitants of these
      traits/conditions lead to major medical illnesses. Benzodiazepines have effects,
      e.g. blunting of stress hormone responses, that could prevent disease in persons
      so predisposed. It will be necessary to identify subgroups with sufficiently high
      absolute rates of disease risk to justify pharmacological interventions, and then
      to carry out controlled prevention trials to document the benefits, before such
      approaches can be recommended for the general population. This approach (use of
      drugs when other measures fail) is now standard for more traditional risk
      factors, such as hyperlipidemia and hypertension. In contrast to primary
      prevention, a stronger case can be made for the use of benzodiazepines in
      secondary prevention. Research has shown benzodiazepine treatment to improve
      control of angina and to reduce "silent ischemia", directly suggesting clinical
      benefits to be gained from the effects of benzodiazepines to reduce stress
      hormone responses. While benzodiazepines have long been prescribed for the
      postmyocardial infarction patient, there are no controlled clinical trials
      documenting such benefits. These are now clearly in order so that the use of
      benzodiazepines in coronary patients can be advised on a rational basis.

PMID- 1980701
TI  - Short-acting versus long-acting benzodiazepines: discontinuation effects in panic
      disorders.
AB  - An increasing body of evidence suggests that benzodiazepines--which have long
      been considered the drugs of choice in the treatment of various anxiety disorders
      due to their relative lack of side effects, lack of adverse drug reaction, their
      safety, and increased efficacy over other agents--are effective in the treatment
      of panic disorders. Originally, the benzodiazepines were believed to be devoid of
      dependence-inducing properties, even at high doses. Recent evidence, however,
      suggests that discontinuation of both high and normal doses of both short- and
      long-acting benzodiazepines generally results in similar withdrawal symptoms,
      including anxiety and sleep and perceptual disturbances. This article presents a
      brief review of benzodiazepine withdrawal, with an emphasis on the
      discontinuation of these drugs following treatment of panic disorders. In
      particular, short-acting and long-acting drugs may present different features
      following long-term treatment and withdrawal. Preliminary results from a study
      comparing alprazolam and diazepam are presented to illustrate this point in
      contrast to expectations: the problems associated with withdrawal of both agents
      were comparable.

PMID- 1980702
TI  - Benzodiazepine discontinuation syndromes.

PMID- 1980703
TI  - A practical approach to benzodiazepine discontinuation.
AB  - Non-medical use of benzodiazepines is rare among patients with anxiety disorders.
      Numerous studies have found that non-medical use, or abuse, of benzodiazepines
      occurs usually among patients with histories of alcohol and drug abuse--those who
      use those drugs to get "high". This article distinguishes between medical and non
      medical use of benzodiazepines in clinical practice, and offers practical
      approaches to discontinuation of benzodiazepine treatment for both medical and
      non-medical users of those medicines. The major barrier to clear thinking about
      the abuse of benzodiazepines is the confusion of "addiction" and "withdrawal".
      Addiction means high, unstable dosing outside medical and social boundaries for
      "recreational" purposes, loss of control over use, and continued use despite
      clear evidence of harm. Alcoholism and heroin addiction are typical examples of
      addiction (Kalant, 1989). In contrast, withdrawal is a pharmacological
      consequence of discontinuation of a substance on which a person has become
      dependent. Many drug-addicted people have only minor withdrawal symptoms when
      they stop drug use. Many medical patients, with no evidence of addiction, have
      withdrawal symptoms when they stop treatment, especially when they stop abruptly
      (e.g. surgical patients using narcotic analgesics and epileptics using
      benzodiazepines or barbiturates in their treatment). Addiction to
      benzodiazepines, in the sense of loss of control over use and continued despite
      harm, is virtually limited to people with pre-existing drug or alcohol abuse,
      while withdrawal symptoms after prolonged daily use are common among medical
      users of benzodiazepines. The serious nature of both drug abuse and anxiety
      disorders is not emphasized sufficiently during medical school or in the
      professional literature. The distress and disability from which both groups of
      patients and their families suffer is profound. Fortunately, both drug abuse and
      anxiety patients receive tremendous benefit from successful treatments, both
      pharmacological and nonpharmacological (DuPont, 1986a; DuPont, 1984). This
      article discusses the use of benzodiazepines in two distinct populations--drug
      abusers and patients with anxiety disorders--and helps clinicians distinguish
      between the use of benzodiazepines in the two groups. The central distinction
      made in this article is reflected in the common use of the words "drugs" and
      "medicines". The former term often denotes non-medical substance use, while the
      latter term refers to traditional pharmacotherapy.

PMID- 1980704
TI  - The GABAA/benzodiazepine receptor: implications for the molecular basis of
      anxiety.

PMID- 1980705
TI  - Seasonal abundance and diel landing periodicity of Sabethes chloropterus
      (Diptera: Culicidae) in Trinidad, West Indies.
AB  - The seasonal occurrence and diel landing periodicity of Sabethes chloropterus
      (Humboldt) was studied weekly for 1 yr using the human bait catch in the Pt.
      Gourde Forest, Trinidad, W.I. Population abundance remained low throughout the
      dry season (16%) but increased after the onset of the rains in May and peaked by
      the middle of the rainy season (July-October). The diurnal periodicity of landing
      was unimodal during the wet season with a major peak between 1200-1600 hours and
      bimodal during the dry season with peaks at 0800-1000 and 1200-1400 hours. This
      study documents for the first time the periodicity of landing by Sa. chloropterus
      at ground level and suggests reasons for failure to detect the yellow fever virus
      at this level.

PMID- 1980706
TI  - Isolation of Escherichia coli expressing 987P fimbrial antigen from suckling
      piglets.

PMID- 1980707
TI  - [21st Congress of the Society for Nephrology, Badgastein, 23-26 September 1990.
      Proceedings].

PMID- 1980708
TI  - Poorly expressed CD2 antigen on the leukemic cells of adult T-cell leukemia
      implicate more aggressive clinical course?

PMID- 1980709
TI  - [Prolactinoma is more frequent among men than among women. A dopamine agonist is
      effective in the treatment].

PMID- 1980710
TI  - [Increased incidence of testicular retention. Hormonal treatment is more and more
      common].

PMID- 1980711
TI  - Mannose-sensitive haemagglutination in the absence of piliation in Escherichia
      coli.
AB  - The relationship between type 1 pilus structure and the mannose-sensitive adhesin
      was investigated by analysing the properties of an 11.2 kb fragment of DNA
      derived from the chromosomal pil region of a type 1 piliated uropathogenic strain
      of Escherichia coli. The recombinant plasmids pHA9 and pSJH9, containing the
      cloned fragment, conferred a mannose-sensitive haemagglutination (MSHA)-positive
      but non-piliated phenotype on recipient cells of ORN104. Most of the DNA
      sequences homologous to the pilA and hyp genes were not present in the 11.2 kb
      insert, and the genetic information necessary for MSHA in the absence of
      piliation spanned a 6.5 kb region of the cloned fragment. The polypeptides
      expressed by pSJH9 were examined in minicells and Tn1000 insertions in three
      genes encoding proteins of molecular weights 90 kD, 29 kD and 17 kD abolished the
      MSHA phenotype.

PMID- 1980712
TI  - The role of direct oligonucleotide repeats in gonococcal pilin gene variation.
AB  - Previous studies indicate that gonococcal pilin phase and antigenic variation
      occur by intragenomic pilin gene recombination, the outcome of which resembles
      that of gene conversion. During such transitions, the expressed complete pilin
      gene (pilE) acquires a novel sequence corresponding to that of a silent pilin
      gene (pilS). In the present study, we find that internal deletions of pilE can
      produce pilus-/pilus+ phase transitions: direct oligonucleotide repeats in the
      pilin-encoding portion of pilE bracket the deleted segments. A novel, orthodox
      pilE is formed upon repair of the internal deletions, with pilS sequence probably
      acting as a template for repair. Such deletion/repair of pilE is suggested as a
      principal mechanism underlying gonococcal pilus variation.

PMID- 1980713
TI  - Type V collagen as the target for type-3 fimbriae, enterobacterial adherence
      organelles.
AB  - Tissue-binding specificity of the type-3 fimbriae of pathogenic enteric bacteria
      was determined using frozen sections of human kidney. A wild-type Klebsiella sp.
      strain and the recombinant strain Escherichia coli HB101(pFK12), both expressing
      type-3 fimbriae, as well as the purified type-3 fimbriae effectively bound to
      sites at or adjacent to tubular basement membranes, Bowman's capsule, arterial
      walls, and the interstitial connective tissue. Bacterial adherence to kidney was
      decreased after collagenase treatment of the tissue sections. Recombinant strains
      expressing type-3 fimbriae specifically adhered to type V collagen immobilized on
      glass slides, whereas other collagens, fibronectin or laminin did not support
      bacterial adherence. In accordance with these findings, specific binding of
      purified type-3 fimbriae to immobilized type V collagen was demonstrated.
      Specific adhesion to type V collagen was also seen with the recombinant strain
      HB101(pFK52/pDC17), which expresses the mrkD gene of the type-3 fimbrial gene
      cluster in association with the pap-encoded fimbrial filament of E. coli, showing
      that the observed binding was mediated by the minor lectin (MrkD) protein of the
      type-3 fimbrial filament. The interaction is highly dependent on the conformation
      of type V collagen molecules since type V collagen in solution did not react with
      the fimbriae. Specific binding to type V collagen was also exhibited by type-3
      fimbriate strains of Yersinia and Salmonella, showing that the ability to use
      type V collagen as tissue target is widespread among enteric bacteria.

PMID- 1980714
TI  - Physiology and pathophysiology of pulmonary circulation.
AB  - The lungs provide not only respiratory function, but also are involved in
      metabolism and maintaining homeostasis. The lungs receive the entire cardiac
      output, circulating blood cells and hormones. The metabolically active vascular
      endothelial cell lining participates in degrading and synthesizing various
      hormones and vasoactive substances which affect the pulmonary as well as systemic
      circulation. The normal state is maintained through complex interaction of the
      circulating hormones, maturation of the system, the physiological state of the
      lung cells and metabolism. Any noxious stimulus can disrupt this delicate balance
      and adversely affect the metabolism of various substances, thus producing an
      abnormal state. In this review, some of these factors including therapeutic
      implications are discussed.

PMID- 1980715
TI  - [The prevention of traumatic dentoalveolar lesions in pedodontics].

PMID- 1980716
TI  - Ca2+ redistribution from bound to free form is required for tumor necrosis factor
      actions in 30A5 preadipocytes.
AB  - Tumor necrosis factor/cachectin (TNF) inhibits differentiation of 30A5
      preadipocytes into adipocytes. In this process, TNF inhibits the expression of
      the gene for acetyl-coenzyme-A carboxylase, the rate-limiting enzyme for
      biogenesis of long chain fatty acids. One of the early reactions caused by TNF is
      the Ca2+ redistribution of Ca2+ from the bound form to the free form. This Ca2+
      redistribution results in a transient Ca2+ efflux. High concentrations of Mg2+
      inhibit Ca2+ redistribution and efflux. This inhibition reverses the repression
      of acetyl-coenzyme-A carboxylase and reverses the TNF inhibition of the
      differentiation of 30A5 preadipocytes into adipocytes. This indicates that Ca2+
      redistribution between the bound and the free form is an obligatory event in the
      sequence of actions caused by TNF in 30A5 cells.

PMID- 1980717
TI  - Human factor IXLincoln Park: a molecular characterization.
AB  - Using genomic DNA prepared from peripheral blood samples of a patient with factor
      IX deficiency, all eight exons as well as sequences around the splice junctions
      and putative promoter region of human factor IX DNA have been subjected to
      polymerase chain reaction (PCR) amplification and sequenced. Comparison of these
      sequences with normal factor IX gene sequences revealed an insertion in exon VIII
      that resulted in the alteration of 11 amino acids and the addition of 23 amino
      acids, all at the carboxy terminal of factor IX. This insertion destroys an Msp I
      restriction site; carrier detection and antenatal diagnosis in affected kindreds
      can be performed by testing for the absence of this site. This is the first
      characterization of a mutation in which insertion in the carboxy terminal region
      of factor IX causes factor IX deficiency. The genetic change in factor IX in this
      patient is called Factor IXLincoln Park.

PMID- 1980718
TI  - CGP 28014, a new inhibitor of cerebral catechol-O-methylation with a non-catechol
      structure.
AB  - CGP 28014 (N-(2-pyridone-6-yl)-N',N'-di-n-propylformamidine) or its
      methanesulfonate salt CGP 28014 A was suspected to be a catechol-O-methyl
      transferase (COMT) inhibitor because it was found to reduce the levels of
      homovanillic acid (HVA) and to increase those of 3,4-dihydroxyphenylacetic acid
      (DOPAC) in the rat striatum, after oral or intraperitoneal administration. These
      effects were maintained after repeated administration. The compound was only
      weakly active as a COMT inhibitor in vitro. However, its effect on striatal HVA
      and DOPAC was not prevented by pretreatment with the inhibitor of microsomal drug
      metabolizing enzymes in the liver, proadifen, indicating that, if CGP 28014 acts
      as a prodrug, its conversion to the active compound is not by oxidative
      metabolism in the liver. Also, there was no evidence that conversion to 2-amino-6
      hydroxypyridine could explain its effects. The in vivo effect of CGP 28014 was
      substantiated in two additional in vivo test systems. Thus, it inhibited the
      accumulation of 3-methoxytyramine in the rat striatum after MAO inhibition by
      clorgyline, and the formation of O-methyl-DOPA from exogenously administered
      DOPA. It proved to be equipotent or nearly so with tropolone, and also showed a
      similar duration of action. Similar to tropolone, it increased S
      adenosylmethionine levels in the striatum. Pyrogallol, on the other hand,
      decreased them, because being a substrate of COMT, it consumes methyl groups.
      This suggests that CGP 28014 does not inhibit COMT because it is a substrate of
      the enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1980719
TI  - Analysis of alpha-2 adrenergic agonist effects on the delayed nonmatch-to-sample
      performance of aged rhesus monkeys.
AB  - The administration of alpha-2 adrenergic agonists to aged monkeys has been shown
      to ameliorate their cognitive deficits on the delayed response (DR) task, a test
      of spatial working memory (3,5). The present experiment tested whether the alpha
      2 agonists, clonidine and guanfacine, would also improve working memory for
      object feature recognition, as tested by the delayed nonmatch-to-sample (DNMS)
      task. Five aged monkeys were trained on DNMS and were found to have mild
      performance deficits comparable to those reported previously for monkeys of
      similar age (32). However, during the subsequent two years of drug testing, the
      animals' baseline performance steadily improved, and conditions had to be made
      progressively more difficult to produce errors in performance. Clonidine and
      guanfacine significantly altered the DNMS performance of the aged monkeys, but
      drug-induced improvement was not as robust for DNMS as it was for DR. Clonidine
      produced a triphasic dose/response curve: Impairment was observed at both very
      low and high doses, while modest improvement was seen in the middle dose range
      (average maximal improvement of 21 +/- 2.4%). Although improvement could
      occasionally be replicated for some doses, the clonidine dose/response curves
      were remarkably inconsistent in the middle dose range. Similarly, doses of
      guanfacine which had previously produced optimal improvement on the DR task,
      produced only small but significant improvement in DNMS performance (average
      improvement of 11 +/- 3% for the 0.00011-0.000011 mg/kg dose range).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1980720
TI  - Age-related subsensitivity of cerebellar Purkinje neurons to locally applied beta
      1-selective adrenergic agonist.
AB  - Previous electrophysiological studies in aged rats have revealed a number of
      deficits in noradrenergic neurotransmission in the central nervous system. Such
      deficits include subsensitivity to the depressant effects of norepinephrine on
      cerebellar Purkinje neurons, which has been attributed specifically to altered
      beta adrenergic receptor-mediated processes. The objective of this study was to
      determine which beta adrenergic receptor subtype, beta 1 or beta 2, is
      responsible for this age-related subsensitivity. The effects of beta 1 and beta 2
      agonists on spontaneous activity of Purkinje neurons was first examined in young
      rats and the selectivity of these agents was validated using selective beta 1 and
      beta 2 antagonists. The effects of the selective beta 1 and beta 2 agonists were
      then compared in young (3-month-old) and aged (18- and 26-month-old) Fischer 344
      rats. These agents were applied to Purkinje neurons by pressure microejection
      from multibarreled micropipettes and the change in neuronal action potential
      discharge rate was recorded. Both dobutamine, a beta 1-selective agonist, and
      zinterol, a beta 2-selective agonist, induced dose-dependent inhibitions of
      Purkinje cell firing rate. Dobutamine-induced inhibitions were blocked by the
      selective beta 1 antagonist, ICI 89406 and not by the beta 2-selective
      antagonist, ICI 118551; conversely, zinterol-induced inhibitions were not blocked
      by ICI 89406 but were blocked by the presence of ICI 118551. Purkinje neurons of
      both groups of aged rats were significantly less sensitive to locally applied
      dobutamine than Purkinje cells of young rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1980721
TI  - Selective age-related changes in neuronal markers and smooth muscle reactivity in
      cerebrovascular beds of Fischer 344 rats.
AB  - Choline accumulation, choline acetyltransferase (ChAT) and glutamic acid
      decarboxylase (GAD) activities were measured simultaneously in various
      cerebrovascular beds and brain areas from Fischer 344 rats aged 4.5 and 22
      months. A slight (25%) but not significant decrease in choline accumulation was
      observed concomitantly with a significant increase (187%, p less than 0.05) in
      ChAT activity in the major cerebral arteries of the 22-month-old rats. In small
      cortical pial vessels and selected brain regions, cholinergic and GABAergic
      biochemical markers remain unaltered in aged rats. The vasomotor reactivity of
      the basilar artery was investigated in rats of 4.5, 12, 22 and 30 months of age.
      In the 22-month-old rats, maximal responses to 5-hydroxytryptamine (-25%, no
      significant) and prostaglandin F2 alpha (-30%, p less than 0.05 by ANOVA) were
      less intense as compared to other age-groups despite preserved contractile
      responses to dopamine, uridine triphosphate or a depolarizing concentration of
      K+. Relaxations induced by histamine, acetylcholine, noradrenaline, adenosine and
      somatostatin were strictly comparable among the different age-groups. The
      sensitivity of the basilar artery to all vasoactive agents failed to demonstrate
      any correlation with age. Our study suggests that cerebrovascular cholinergic and
      GABAergic markers undergo minor and selective changes with increasing age.
      Further, basilar artery vasomotor functions appeared relatively spared by the
      aging process despite age-related selective decreases in contractile responses to
      5-hydroxytryptamine and prostaglandin F2 alpha.

PMID- 1980722
TI  - Sex-related alterations in hypothalamic tyrosine hydroxylase after neonatal
      monosodium glutamate treatment.
AB  - This study compared tyrosine hydroxylase (TH) mRNA signal levels, relative
      quantity of TH protein, and the catalytic activity of TH in the
      tuberoinfundibular dopaminergic neurons (TIDA) of male and ovariectomized (OVEX)
      female rats. In addition, the effects of monosodium glutamate (MSG) neurotoxicity
      on these parameters of TH regulation were evaluated. Neonatal rats were injected
      with MSG (4 mg/g body weight) or 10% sodium chloride (controls) on alternate days
      for the first 10 days of life. Females were ovariectomized on day 45 of age, and
      all rats were used between 60 and 80 days of age. The TH mRNA signal levels, as
      assessed by an in situ hybridization technique, were 2-fold higher in control
      females than in control males, whereas the number of TH mRNA-containing cells was
      similar between sexes. The TH immunostainings of the TIDA perikarya in the
      arcuate nucleus and of the nerve terminals in the median eminence were
      qualitatively more intense in females than males. The catalytic activity of TH,
      as determined by in vitro DOPA accumulation in the stalk-median eminence, was 3
      fold greater in females than males. Neonatal MSG-treatment resulted in a marked
      reduction in the number of TH mRNA-containing cells and TH-immunopositive cells
      in the arcuate nucleus of both sexes, as well as a decrease in the intensity of
      TH immunostaining in the median eminence. The cellular mRNA signal levels for TH
      were markedly reduced in females after MSG treatment, but were unchanged in
      males. MSG treatment reduced TH activity to 20% of control levels in females, but
      did not alter enzyme activity in males.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1980723
TI  - Hypothalamic neurochemistry and feeding behavioral responses to clonidine, an
      alpha-2-agonist, and to trifluoromethylphenylpiperazine, a putative 5
      hydroxytryptamine-1B agonist, in genetically obese Zucker rats.
AB  - Genetically obese Zucker rats are hyperphagic, hyperinsulinemic and hyperlipemic.
      In order to investigate pathophysiological mechanisms underlying hyperphagia in
      these animals, monoamine metabolism and turnover were studied in discrete
      hypothalamic nuclei known to participate in the control of feeding behavior.
      Neurochemical studies in genetically obese Zucker rats and in their lean
      littermate controls were complemented by investigating feeding behavioral
      responses to the acute administration of clonidine (15 and 30 micrograms/kg
      i.p.), an alpha 2-adrenoceptor agonist, and to trifluoromethylphenylpiperazine
      (TFMPP; 1, 2 and 5 mg/kg s.c.), a putative serotonergic 5-hydroxytryptamine-1B
      receptor agonist. Obese Zucker rats had significantly lower concentrations of 5
      hydroxyindoleacetic acid, the main deaminated metabolite of 5-hydroxytryptamine,
      in the nucleus paraventricularis (PVN) and in the nucleus ventromedialis (VMN),
      when compared to their lean littermate controls. The rate of accumulation of 5
      hydroxytryptophan after decarboxylase inhibition was reduced in the PVN, nucleus
      supraopticus, nucleus periventricularis and nucleus suprachiasmaticus of the
      obese rats. No differences were observed in basal concentrations of
      norepinephrine, dopamine or 3,4-dihydroxyphenylacetic acid between obese and lean
      Zucker rats in the brain areas studied. However, the rate of accumulation of 3,4
      dihydroxyphenylalanine was lower in the VMN and in the median eminence of the
      obese rats. The feeding behavioral tests showed significantly augmented
      hyperphagic responses to clonidine in obese Zucker rats. The anorexic effect of
      TFMPP was similar in both phenotypes. It is concluded that serotonergic activity
      is reduced in obese Zucker rats, particularly in the PVN, which plays a key role
      in the control of feeding behavior. The reduced serotonergic activity may be
      associated with enhanced alpha 2-adrenoceptor-mediated feeding responses in obese
      Zucker rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1980724
TI  - Multihormonal control of pre-pro-somatostatin mRNA levels in the periventricular
      nucleus of the male and female rat hypothalamus.
AB  - The influence of sex steroids as well as the possible involvement of dopaminergic
      pathways in the modulation of pre-pro-somatostatin (SS) mRNA levels was
      investigated by quantitative in situ hybridization in the hypothalamic
      periventricular nucleus (PeN) in adult male and female rats. In situ
      hybridization was performed using a [35S]-labeled cDNA probe encoding pre-proSS
      mRNA. Gonadectomy performed 14 days earlier decreased the mean number of silver
      grains/neuron corresponding to the relative pre-proSS mRNA levels by 22% in male
      and by 18-28% in female rats. A 14-day treatment with the nonaromatizable
      androgen dihydrotestosterone (DHT) increased the mean number of silver
      grains/neuron by 34-40% in gonadectomized animals of both sexes. Moreover,
      administration of 17 beta-estradiol (E2, 0.25 microgram twice daily) increased
      pre-proSS mRNA levels by 40% in ovariectomized (OVX) animals. Such treatment with
      E2 or DHT changed the frequency distribution profile of the hybridization signal
      intensity, thus increasing the percentage of highly labeled neurons (greater than
      or equal to 61 grains/neuron) by 10 to 12-fold. A 14-day treatment with the D2
      dopamine receptor agonist bromocriptine (BRO) increased pre-proSS mRNA levels by
      15 and 28% in intact female and OVX animals, respectively, while the dopaminergic
      antagonist haloperidol (HAL) decreased the value of this parameter by 20 and 30%.
      Furthermore, BRO increased pre-proSS mRNA levels by 10 and 20% in intact and
      castrated male rats, respectively, whereas HAL decreased pre-proSS mRNA levels by
      25 and 14% in the same groups of animals. Administration of E2 in combination
      with HAL in OVX animals increased pre-proSS mRNA levels by 70% compared to those
      measured in OVX animals treated with HAL alone. In HAL-treated castrated male
      rats, administration of DHT increased the relative pre-proSS mRNA levels by 35%
      compared to those measured in castrated animals treated with HAL alone. The
      present data clearly demonstrate that androgens and estrogens as well as dopamine
      mediated mechanisms could play a regulatory role in pre-proSS mRNA levels in
      somatostatinergic neurons in the hypothalamic PeN in both male and female rats.

PMID- 1980725
TI  - Evaluation of the role of prolyl endopeptidase and pyroglutamyl peptidase I in
      the metabolism of LHRH and TRH in brain.
AB  - Intraneuronal peptide regulatory mechanisms are still poorly understood. The
      cytosolic enzymes prolyl endopeptidase (EC 3.4.21.26) and pyroglutamyl peptidase
      I (E.C.3.4.19.3) degrade both TRH and LHRH. Previous studies from this laboratory
      have not supported a role for these enzymes in the control of TRH levels. These
      studies have now been extended to cell and organ cultures and examine the effects
      of enzyme inhibition on LHRH. Exposure of dispersed hypothalamic cells or median
      eminences in culture to Z-Pro-Prolinal and pyroglutamyl diazomethyl ketone,
      specific inhibitors of prolyl endopeptidase and pyroglutamyl peptidase I
      respectively, did not change TRH content or recovery of released TRH. In vivo and
      in vitro treatment with these inhibitors did not modify the content of LHRH or
      recovery of this peptide upon release from several brain regions except in the
      olfactory bulb where an unexpected decrease in levels was observed. Olfactory
      bulb levels of TRH also decreased but only after prolonged in vivo inhibitor
      treatment. The decrease in olfactory bulb LHRH and TRH could not be accounted for
      by enzyme induction and is likely due to a non-specific or indirect effect of the
      inhibitors on the processing of these peptides. These studies demonstrate that
      levels of LHRH and TRH in brain are not controlled by cytosolic peptidases.

PMID- 1980726
TI  - Effect of somatostatin on the canine gallbladder motility.
AB  - Somatostatin (SOM) at doses up to 1 microgram was not effective on the motility
      of canine and guinea pig gallbladder smooth muscle preparations in vitro. When
      the preparations were contracted by field electrical stimulation (0.7 ms, 40 Hz)
      the cholecystokinin octapeptide (CCK OP) enhanced these contractions while SOM
      inhibited them. These effects were accompanied, respectively, by an increase or a
      decrease in [3H] acetylcholine (ACh) release in the intrinsic cholinergic nerve
      terminals. SOM (0.5 to 2 micrograms/kg i.v.) inhibited the spontaneous and the
      CCK OP-activated gallbladder pressure in conscious dogs. The effect of atropine
      (10-50 micrograms/kg) was similar to that of SOM when injected intravenously in
      conscious dogs. It is suggested that the inhibitory effect of SOM on gallbladder
      pressure in conscious dogs is probably mediated by a decrease in ACh release by
      cholinergic neurons.

PMID- 1980727
TI  - Evaluation of psychotropic drug consumption related to psychological distress in
      the elderly: hospitalized vs. nonhospitalized.
AB  - The use of psychotropic drugs in general has become more extended in the past 20
      years. The elderly, particularly geriatric inpatients, are the group with the
      highest consumption. The aim of the present study was to evaluate in two groups
      of elderly, hospitalized patients (H) vs. nonhospitalized subjects (nH),
      psychotropic drug consumption related to psychological distress. This was carried
      out in a total 238 subjects aged above 65 years (112 geriatric inpatients and 126
      interviewed in social welfare centers). Sociodemographic, clinical and
      pharmacological data, general health and psychological distress were evaluated.
      The latter was assessed by means of the Symptom Distress Checklist (SCL-90) which
      included 9 subscales. 23% of the subjects received psychotropic drugs (P), of
      which 84% were benzodiazepines, 10% antidepressants and 1.5% antipsychotics.
      After evaluating the SCL-90 subscales, it was noted that anxiety, depression and
      obsessiveness/compulsiveness scored higher in P subjects than in those not
      receiving psychotropic drugs (nP). When treated nH and H were analyzed
      separately, it was observed that the former scored higher in anxiety and
      depression, while the latter showed higher scores in anxiety and
      obsessiveness/compulsiveness. Considered globally, the H group compared to nH
      showed higher scores in depression. Although evaluating psychotropic drug
      utilization in geriatric patients is complex due to the large number of
      influencing factors, SCL-90 has proved to be useful for assessing the qualitative
      aspects of this drug consumption in the elderly.

PMID- 1980728
TI  - [500 days of somatostatin treatment].
AB  - A group of 11 patients received somatostatin for a minimum period of 30 days.
      Patients affected by pancreatic fistulae following either chronic and acute
      pancreatitis of surgery were admitted to the study. Other published reports are
      not explicit about the possible side-effects of such a long period of full-dose
      therapy (lasting at least twice the recommended cycle). In this case, having been
      forced to continue therapy, no significant side-effects were observed and the
      therapy retained its effectiveness and tolerability up to the end of the study.

PMID- 1980729
TI  - Intrathecal N-methyl-D-aspartate induces hyperexcitability in rat dorsal horn
      convergent neurones.
AB  - We have investigated the effects of intrathecal (i.t.) N-methyl-D-aspartate
      (NMDA) and an NMDA antagonist D-2-amino-5-phosphonovalerate (APV) on spontaneous
      and evoked activity in rat dorsal horn convergent neurones. Extracellular
      recordings were made from 54 convergent neurones located in both the superficial
      and deep dorsal horn. NMDA induced a dose-dependent increase in the spontaneous
      firing rate of convergent neurones, with 1 microM and 1 mM NMDA producing firing
      rates significantly greater than i.t. saline. In addition, NMDA induced
      hyperexcitability to subsequent noxious mechanical stimuli at 1 microM and 1 mM,
      and to innocuous stimuli at 1 mM. The NMDA-induced spontaneous hyperexcitability
      was reversed by pretreatment with 1 microM APV i.t. Diffuse noxious inhibitory
      controls (DNIC) applied to areas of the body remote from the receptive field also
      inhibited the NMDA-induced effects. There was no difference between the responses
      of superficial and deep dorsal horn neurones, suggesting a uniform excitatory
      action of NMDA on convergent neurones. Our results support a role for the NMDA
      receptor in mediating a central component of hyperalgesia, at the level of the
      spinal cord dorsal horn.

PMID- 1980730
TI  - Characterization of the presynaptic calcium channels involved in glutamate
      exocytosis from rat hippocampal mossy fiber synaptosomes.
AB  - Calcium antagonists inhibit both the Ca2(+)-dependent and -independent release of
      endogenous glutamate from intact synaptosomes. In the present study, the
      inhibitory potency of several different classes of calcium antagonists were
      determined under conditions that control for an effect of these compounds on the
      Ca2(+)-independent component of glutamate release. The following order of
      inhibitory potency was derived: flunarizine and cinnarizine greater than
      diltiazem greater than verapamil, nifedipine and nimodipine greater than omega
      conotoxin much greater than amiloride, phenytoin, gadolinium and nickel. Only the
      diphenylpiperazine derivatives inhibited Ca2(+)-dependent glutamate release with
      an IC50 value of less than 10(-5) M. This finding indicates that no one type of
      presynaptic calcium channel predominantly mediates Ca2(+)-dependent glutamate
      release from hippocampal mossy fiber terminals. It is suggested that the
      exocytosis of glutamate from rat hippocampal mossy fiber synaptosomes may be
      mediated by multiple types of calcium channels.

PMID- 1980731
TI  - Dopaminergic drugs influence the intensity of catalepsy induced by
      microinjections of carbachol into the reticular formation.
AB  - Carbachol microinjections into the mesencephalic and pontine reticular formation
      in rats induced intense and long-lasting catalepsy. Systemically administered
      haloperidol potentiated, while apomorphine and L-DOPA reduced the cataleptogenic
      effect of carbachol. These results indicate the existence of functional relations
      between the cholinergic cataleptogenic mechanism in the reticular formation and
      the dopaminergic system. They are interpreted in the light of known anatomical
      ascending and descending interconnections between the reticular formation and
      basal ganglia.

PMID- 1980732
TI  - Differences in beta-adrenergic regulation of cyclic AMP formation in cerebral
      cortical slices of the rat and spiny mouse--Acomys cahirinus.
AB  - In both the rat and Acomys cahirinus the adrenergic cyclic AMP generating system
      in the brain is dependent not only on beta-, but also on alpha-adrenoceptors. The
      relative role of alpha-adrenoceptors is much greater in the Acomys cahirinus.
      This feature makes the Acomys an interesting animal model for investigating the
      role of alpha-beta-adrenoceptor coupling in generation of cyclic AMP and the
      mechanism of action of antidepressant treatment.

PMID- 1980733
TI  - [Magnesium sulfate as adjuvant in beta-2-sympathicomimetic inhalation therapy of
      bronchial asthma].
AB  - The protective effects of inhaled MgS04 on exercise-induced asthma were studied
      in 13 children aged 6-13 years. The patients performed 6 min. running test on 3
      separate days. Spirometry (FEV1, SRAW, VK, PF) was recorded on each test day 10
      min. after medicament inhalation directly before and instantly, 2, 5, 10 and 20
      min after the running test. t-tests on the mean revealed no significant effects
      on spirometric measurements (p less than 0.1), but in 6 patients MgS04-inhalation
      prevented FEV1--decreases greater than 20%. The combination gave better
      protection compared to salbutamol alone demonstrated from the measurements after
      exercise testing. Thus, MgS04-inhalation could be useful in the protective
      treatment of asthma.

PMID- 1980734
TI  - The effect of somatostatin on insulin and glucose levels during insulin infusion
      in anesthetized dogs.
AB  - The purpose of the study was to examine the transhepatic and peripheral effects
      of somatostatin (SN) infusion on plasma glucose and insulin during insulin (IN)
      infusion. Hepatic blood flow was measured electromagnetically during intermittent
      sampling from the portal and hepatic veins, femoral artery, and right external
      jugular vein. Hepatic blood flow [sum of portal vein (PV) and hepatic artery] was
      similar during IN or IN + SN infusions. IN concentrations decreased in the portal
      vein from 374.8 +/- 50.3 to 295.8 +/- 25.9 pM (p less than 0.01) when SN was
      infused with IN. Hepatic venous plasma IN concentration also decreased from 143.6
      +/- 26.6 to 88.3 +/- 10.1 pM (p less than 0.01). Plasma IN concentrations in the
      femoral artery and jugular vein remained unchanged. Hepatic insulin extraction
      changed from 64 +/- 4% during IN to 72 +/- 3% during IN + SN (p less than 0.01).
      Hepatic clearance and total body clearance were unchanged. Peripheral venous
      glucose with a nadir of 3.82 +/- 0.2 mM during IN alone decreased to a nadir of
      3.16 +/- 0.27 mM (p less than 0.01) during IN + SN infusion. Mean portal venous
      glucose concentrations were 5.0 +/- 0.27 and 3.4 +/- 0.19 mM, respectively (p
      less than 0.01). In two additional experiments in which endogenous C-peptide
      concentrations were examined in the portal vein and femoral artery, C-peptide
      levels were lower during IN + SN compared to IN alone. We conclude that SN used
      to suppress endogenous insulin secretion increases hepatic insulin extraction,
      lowers glucose concentrations, and suppresses endogenous C-peptide levels to a
      greater extent than insulin infusion alone.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1980735
TI  - Pancreatic polypeptide and other pancreatic hormones in spontaneously diabetic
      BB/W rats.
AB  - The BB/W strain of rats develop spontaneous insulin-dependent diabetes. Diabetic
      BB/W rats have a marked insulinopenia and greatly diminished levels of insulin in
      their pancreas. Using a radioimmunoassay for rat pancreatic polypeptide (PP), we
      have examined the content of PP in extracts of the total pancreas and also the
      regional PP concentration of the three pancreatic lobes. Radioimmunoassays for
      glucagon, somatostatin (SRIF) and insulin were also made on these extracts.
      Compared with nondiabetic BB/W rat pancreas, pancreatic extracts from severely
      diabetic BB/W rats contained 30% as much PP, 31% as much glucagon, 19% as much
      SRIF, and 0.5% as much insulin. The rat PP radioimmunoassay was used to determine
      the elution pattern of PP-like antigens in gel chromatography fractions and to
      measure in vitro secretion of PP from perifused pancreatic slices obtained from
      diabetic and nondiabetic animals. PP-like immunoreactivity was observed in two
      zones in the elution from the gel columns when extracts from normal or diabetic
      rats were chromatographed. The major zone of immunoreactivity eluting at the
      volume expected for intact monometric rat PP accounted for 67% of the PP-like
      immunoreactivity in the case of nondiabetic rats and greater than 80% of the PP
      like immunoreactivity found in extracts from severely diabetic rats. The minor
      zone of PP-like immunoreactivity eluted at a volume similar to the position of
      tetradecapeptide SRIF contained the remainder of detected PP-like
      immunoreactivity. Tissue slices from diabetic rats secreted more PP and glucagon
      than slices from nondiabetic rats when slices were perifused with a medium
      containing leucine, carbachol, and cholecystokinin, even though diabetic pancreas
      has smaller amounts of PP, glucagon, SRIF, and insulin. Stimulated insulin
      secretion was virtually absent when tissue slices from diabetic rats were
      perifused. These results indicate that in the BB/W diabetic rat: (a) pancreatic
      glucagon, PP, and SRIF are moderately decreased and insulin levels are
      drastically reduced, (b) lower levels of degraded or low molecular weight form of
      immunoreactive PP occurs in the diabetic rat pancreas compared to the normal rat,
      (c) the diabetic pancreas secretes more PP and glucagon and much less insulin
      than pancreas from nondiabetic rats when perifused under stimulating conditions.
      The diabetes occurring in the BB/W appears to be a severe type I diabetes
      characterized by reduced content of insulin, glucagon, SRIF, and PP in the
      pancreas of these animals. However, secretion of glucagon and PP were not reduced
      in this in vitro system.

PMID- 1980736
TI  - Spatial filtering and spatial primitives in early vision: an explanation of the
      Zollner-Judd class of geometrical illusion.
AB  - The apparent length and orientation of short lines is altered when they abut
      against oblique lines (the Zollner and Judd illusions). Here we present evidence
      that the length and orientation biases are geometrically related and probably
      depend upon the same underlying mechanism. Measurements were done with an 'H'
      figure, in which the apparent length and orientation of the cross-bar was
      assessed by the method of adjustment while the orientation of the outer flanking
      lines was varied. When the flanking lines are oblique the apparent length of the
      central line is reduced and its orientation is shifted so that it appears more
      nearly at right-angles to the obliques than is in fact the case. Measurements of
      the orientation and length effects were made in three observers, over a range of
      flanking-line angles (90, 63, 45, 34 and 27 deg) and central line lengths (9, 17,
      33 and 67 arc min). The biases increased with the tilt of the flanking-lines, and
      decreased with central line length. The extent of the length bias could be
      accurately predicted from the angular shift by simple trigonometry. We describe
      physiological and computational models to account for the relation between the
      orientation and length biases.

PMID- 1980737
TI  - Human attention: the exclusion of distracting information as a function of real
      and apparent separation of relevant and irrelevant events.
AB  - A leading theory suggests that human vision operates by separate and parallel
      analysis of each of the simple features of the visual scene; but computation of
      the identity of objects, which needs combination of these features, is undertaken
      selectively and only for some parts of the incoming information. It is known that
      the identity of distracting events affects reaction time only for distractors
      spatially close to the reaction signal. This suggests that the selection is
      spatially based; perhaps taking place in the projection areas. Experiments on
      this topic have, however, normally considered events only at a fixed viewing
      distance; in this study different viewing distances were employed. It was found
      that, over the range of conditions used, the ability to exclude irrelevant
      distractors depended upon the true physical separation and not on the angular
      separation at the eye of the observer. Hence the 'attention' system must operate
      at a point later than the computation of true physical location, rather than at
      the very early stage where angular separation only is available.

PMID- 1980738
TI  - Coupled potassium channels induced by arachidonic acid in cultured neurons.
AB  - Exposure of the inside surface of patches of membrane excised from cultured rat
      hippocampal neurons to arachidonic acid (10-100 microM) caused the appearance of
      potassium currents of variable amplitude similar to those activated by GABA or
      baclofen in cell-attached patches. The amplitude of single-channel currents
      increased with time after exposure to 20 or 50 microM arachidonic acid and also
      increased when arachidonic acid concentration was increased from 20 to 50 or 100
      microM. Current-amplitude probability histograms had peaks at integral multiples
      of an 'elementary' current. It is proposed that arachidonic acid or its
      metabolites cause synchronous opening and closing of coupled conducting units (co
      channels) in cell membranes.

PMID- 1980740
TI  - Behaviour of cells mutant for an EGF receptor homologue of Drosophila in genetic
      mosaics.
AB  - The Drosophila homologue of the epidermal growth factor receptor (DEGFr or DER,
      also called torpedo or top) has many mutant alleles that cause either embryonic
      lethality (both early and late), pupal lethality or female sterility, possibly
      corresponding to degrees of hypomorphism. We have studied the clonal behaviour of
      some lethal alleles in genetic mosaics in the imaginal development of thorax,
      head and tergite epidermis. These alleles cause reduced cell viability to
      different degrees (measured in frequency and size of clones), smaller cell sizes,
      abnormal patterning of sensory-organ differentiation and lack of differentiation
      of macro-chaetae and veins. These effects are cell-autonomous but also cause
      abnormal differentiation in wild-type cells surrounding the clones. In addition,
      we have studied the phenotypes of double mutant combinations of viable top
      alleles with wing-pattern mutants, some related to other Drosophila proto
      oncogenes, to reveal gene interactions in the role(s) of DER in cell
      proliferation and differentiation. We discuss how those complex cell-behaviour
      phenotypes and genetic interactions are related to the molecular nature of the
      DER.

PMID- 1980739
TI  - ATP inhibits smooth muscle Ca2(+)-activated K+ channels.
AB  - There has been much recent interest in the roles played by smooth-muscle K+
      channels in protecting cells against ischemic and anoxic insults and in
      therapeutic vaso- and bronchodilation (Buckingham 1990; Longmore & Weston 1990).
      A K+ channel, which is uniquely sensitive to cytoplasmic ATP (KATP), has been
      identified as a likely candidate for mediating these important functions (Standen
      et al. 1989). We now show, by using electrophysiological techniques in three
      different types of smooth muscle, that a large-conductance voltage and Ca2(+)
      sensitive channel, otherwise indistinguishable from the the large-conductance
      Ca2(+)-activated K+ channel (BK channel), is also sensitive to cytoplasmic ATP
      and cromakalim. ATP, in a dose-dependent manner, decreased the probability of
      channel opening (Po) of rabbit aortic, rabbit tracheal and pig coronary artery BK
      channels with a Ki of 0.2-0.6 mM. Cromakalim, 10 microM, partially reversed the
      ATP induced inhibition and increased Po. Our observations raise the possibility
      that the ubiquitous BK channel may play a role during pathophysiological events.

PMID- 1980741
TI  - Active mariner transposable elements are widespread in natural populations of
      Drosophila simulans.
AB  - The occurrence of active, or autonomous, mariner elements was investigated by
      crossing white-peach mutant Drosophila simulans females with wild-type males from
      various geographic origins. From a total of 194 experimental crosses only 17
      failed to produce progeny with eye mosaicism (MOS, i.e. pigmented spots in
      otherwise white-peach eyes). Therefore, active mariner elements inducing somatic
      excision of the copy inserted at the white locus are abundant in all populations
      sampled. In the experimental crosses the frequency of mosaic offspring ranged
      from 0 to 100%, showing that the phenotypic expression is highly variable. The
      MOS phenotype, measured by the number of spots on the eyes, is quite variable
      within the progeny of single crosses. Although a difference was observed in the
      average MOS score (percentage of mosaic flies) between northern and southern
      populations of France, there was no indication of long range variation between
      geographic populations. Neither was there a systematic difference between
      recently collected populations and samples kept several years as isofemale lines.

PMID- 1980742
TI  - Selective coupling of different muscarinic acetylcholine receptors to neuronal
      calcium currents in DNA-transfected cells.
AB  - Acetylcholine (ACh) can inhibit calcium currents (ICa) in nerve cells by
      activating muscarinic ACh receptors (mAChR). There are several different genetic
      subtypes of mAChR. It is not known which subtype(s) are responsible for ICa
      inhibition. To resolve this issue, we measured ICa inhibition by ACh with patch
      clamp recording, by using Ba2+ as charge carrier, in clones of NG108-15
      neuroblastoma x glioma hybrid cells transfected with DNA for mAChRI, II, III and
      IV. Control (non-transfected) cells showed a mean maximum inhibition of peak ICa
      of 12.8 +/- 1.8% (n = 36) at 1 mM ACh. No consistent increase in inhibition was
      detected in vector-transfected cells, or in cells transformed to express mAChRI
      or mAChRIII. In contrast, inhibition was significantly increased in clones
      transformed to express mAChRII or mAChRIV. Inhibition was not correlated with the
      number of muscarinic receptors as determined by 3H-quinuclidinyl benzilate
      binding. Inhibition in both control and transfected cells was prevented by
      pretreatment with pertussis toxin (PTx). Inhibition persisted in the presence of
      extracellular or intracellular dibutyryl cyclic AMP, and hence is not because of
      inhibition of adenylate cyclase. We conclude that the inhibition of neuronal ICa
      is mediated preferentially by mAChRII and mAChRIV, via a PTx-sensitive GTP
      binding protein.

PMID- 1980743
TI  - Radiolabelled cellular blood elements. Proceedings of the 5th International
      Symposium. Vienna, September 10-14, 1989.

PMID- 1980744
TI  - Domains of mental functioning: Attempts at a synthesis. Federal Republic of
      Germany, December 4-8, 1989. Proceedings.

PMID- 1980745
TI  - Metabolism and role of glutamate in mammalian brain.

PMID- 1980746
TI  - In vivo electrochemical measurements in the CNS.

PMID- 1980747
TI  - Cysteine sulphinate (CSA) as an excitatory amino acid transmitter candidate in
      the mammalian central nervous system.

PMID- 1980748
TI  - Laurentian Hormone Conference. proceedings.

PMID- 1980749
TI  - Guanylate cyclase receptor family.
AB  - The plasma membrane forms of guanylate cyclase contain a highly conserved
      catalytic domain, which is also conserved in the soluble form of the enzyme and
      in mammalian adenylate cyclase. A protein kinase-like domain lies to the amino
      terminal side of the catalytic domain and appears to be required for signaling
      via cGMP; it might also signal, itself, through phosphotransferase activity. This
      domain is present in the growth factor receptors, but appears not to be a
      component of other guanylate cyclases or adenylate cyclases. A single
      transmembrane domain then separates the cyclase catalytic and protein kinase-like
      domains from the putative ligand-binding domain. At least two plasma membrane
      forms of gunaylate cyclase (i.e., GC-A and GC-B) have now been identified, and
      their ligand specificities appear to be distinctly different. The tissue/cellular
      distribution of this family of receptors is now of potential importance, since
      specific agonists might differentially regulate physiological processes via the
      secondary messenger, cGMP, dependent on cellular distribution of the receptors.

PMID- 1980750
TI  - Forbeck forum on improved drug delivery to brain tumors.

PMID- 1980751
TI  - [Sympatholytic drugs: inhibitors of sympathetic termination functioning and
      blockaders of adreno-receptors].

PMID- 1980752
TI  - [Sulfasalazine for the treatment of rheumatoid polyarthritis. Results after 36
      months].

PMID- 1980753
TI  - [The characteristics of the action of ethacizine and its combination with digoxin
      and glutamic acid on the hemodynamic indices and myocardial contractile capacity
      in patients with a heart rhythm disorder].
AB  - A study was made of the effect of ethacizine administered in a single dose and
      continuously on myocardial contractility and hemodynamics in 78 patients with
      coronary heart disease, neurocirculatory dystonia and myocardiodystrophy
      suffering from impaired cardiac rhythm. In 28 patients, ethacizine was
      administered in combination with glutamic acid and in 23 with digoxin. In
      patients with coronary heart disease, particularly in those with heart failure,
      ethacizine produced a negative inotropic effect. Introduction into the treatment
      of digoxin or glutamic acid smoothed over the cardiodepressive action of the
      drug. When administered continuously in a dose of 150-300 mg/day, ethacizine is
      an effective antiarrhythmic drug.

PMID- 1980754
TI  - Ipecacuanha asthma: an old lesson.

PMID- 1980755
TI  - [The electrochemical indices of soldered dentures with titanium nitride-based
      multilayered coatings].
AB  - Development of an optimal design of multilayer dentures has involved studies of
      the effects of the material used to make the intermediate layer, its thickness
      and mode of application on the corrosive electrochemical behavior of orthodontic
      articles. Application of intermediate layers was found to reduce the magnitude of
      polarization current and improve the corrosion resistance of a soldered
      structure. The best effect was achieved with the design with a protective coating
      of Cr-Ti composition of stainless steel, applied by vacuum method, and galvanic
      Cr. The corrosion protecting characteristics of this sublayer were found to
      depend on the quality of the soldered junction: if it is defective, the
      protective effect is poor whatever the type of coating. The study has confirmed
      the necessity of protective coatings application to soldered half-finished
      articles and the efficacy of multilayer coatings with the surface layer of
      titanium nitride.

PMID- 1980756
TI  - The structure of the homeodomain and its functional implications.
AB  - The three-dimensional structure of the homeodomain, as determined by nuclear
      magnetic resonance spectroscopy, reveals the presence of a helix-turn-helix
      motif, similar to the one found in prokaryotic gene regulatory proteins. Isolated
      homeodomains bind with high affinity to specific DNA sequences. Thus, the
      structure-function relationship is highly conserved in evolution.

PMID- 1980757
TI  - Adhesive fimbriae produced in vivo by Escherichia coli O139:K12(B):H1 associated
      with enterotoxaemia in pigs.
AB  - Two strains of E. coli O139:K12 (B):H1 were compared in vitro and in the
      intestinal environment. Both strains colonized the small intestines of
      experimentally inoculated pigs and exhibited in vivo a similar relationship to
      the microvillus border as enterotoxigenic E. coli (ETEC). Strain 107/86 grown on
      blood agar expressed numerous long flexible non-haemagglutinating fimbriae which
      were antigenically distinct from the known fimbriae of porcine ETEC. It adhered
      in vitro to porcine enterocyte brush border fragments. Strain 124/76 grown on
      blood agar was devoid of fimbriae and did not adhere to brush border fragments.
      However, fimbriae morphologically and antigenically indistinguishable from those
      of strain 107/86 were detected in the intestinal environment by direct
      immunofluorescence and by immuno electron microscopy.

PMID- 1980758
TI  - Ultrastructure of neutrophilic granulopoiesis in the bone marrow of patients with
      chronic myeloid leukemia (CML). A morphometric study with special emphasis on
      azurophil (primary) and specific (secondary) granules.
AB  - In seven patients with chronic myeloid leukemia (CML) and ultrastructural and
      morphometric study was performed on neutrophilic granulopoiesis in bone marrow
      trephine biopsies. Bone marrow specimens from five patients without hematological
      abnormalities served as controls. In stable phases of CML, abnormalities of the
      maturing granulocytic lineage were most conspicuously expressed by an
      infrequently occurring nuclear disfiguration (blebs and disturbed bridging of
      segments). Morphometric evaluation included the numbers of azurphil (primary) and
      specific (secondary) granules, the cisternal length of the endoplasmic reticulum
      and the area of the mitochondrial profiles. These variables could be determined
      in early and late myeloblasts, promyelocytes, metamyelocytes, band cells and
      mature polymorphonuclear granulocytes. Statistical analysis with regard to
      control specimens demonstrated no significant differences in the total amount of
      neutrophil granules or of the other cell organelles.

PMID- 1980759
TI  - Pancreatic cell proliferation in normal rats studied by in vivo autoradiography
      with 3H-thymidine.
AB  - In vivo 3H-Thymidine autoradiographic investigations of DNA synthesis in acinar,
      islet and duct cells in the pancreas of normal rats showed that activity was
      dependent on age. The proliferation of acinar and islet cells, which was high in
      young animals, decreased exponentially with age; proliferation of the ductal
      cells on the other hand, increased until the animals became mature. These
      findings suggest that the physiological regeneration of acinar and islet cells,
      as well as their replacement after injury in adult animals commences from
      pancreatic ducts.

PMID- 1980760
TI  - Isolation of a growth and mitosis inhibitory peptide from mouse liver.
AB  - The isolation of a liver peptide that inhibits the growth, mitosis rate and
      thymidine incorporation in regenerating liver is described. The peptide has the
      structure Pyroglu-gln-gly-ser-asn, and the deamidated forms are also active. The
      peptide probably belongs to a class of growth inhibitors with a high degree of
      tissue specificity. Two such peptides have previously been isolated from the
      epidermis (Reichelt et al. 1987) and from colonic tissue (Skraastad et al. 1987).

PMID- 1980761
TI  - Renal tissue injury and proliferative response after successive treatments with
      anticancer platinum derivatives and tobramycin.
AB  - The administration of anticancer platinum derivatives such as cisplatin, or
      aminoglycoside antibiotics is frequently associated with tubular necrosis which
      can eventually lead to acute renal failure. Previously, we have shown that renal
      tissue injury induced by these drugs elicits a process of tissue repair involving
      the stimulation of cell proliferation. The present study was undertaken to
      examine the morphological alterations and the proliferative response resulting
      from tobramycin administration to animals previously challenged with the platinum
      derivatives cisplatin and carboplatin. Female Sprague-Dawley rats were treated
      i.p. with cisplatin (8 mg/kg delivered in four daily injections) or carboplatin
      (40 mg/kg given in one injection) and sacrificed 21 or 60 days after drug
      administration. Tobramycin was administered i.p. twice a day at a daily dose of
      10 mg/kg over the ten days preceding sacrifice. At 1 h before sacrifice, each
      animal received i.p. 200 microCi of [3H] thymidine for the measurement of DNA
      synthesis and cell proliferation (determined by histoautoradiography). Successive
      treatments with cisplatin and tobramycin appeared to produce an increase in the
      severity of histopathological alterations such as tubular necrosis and cystic
      degeneration. Moreover, cisplatin pretreatment dramatically increased the
      severity of tobramycin-induced lysosomal phospholipidosis. Histopathological
      alterations were followed by an important proliferative response partly
      associated with tubular regeneration but also due to fibroblastic proliferation
      which led to peritubular fibrosis. Surprisingly, the additive effect of cisplatin
      and tobramycin on renal injury became particularly striking with increasing time
      intervals between treatments. In contrast, successive treatments with carboplatin
      and tobramycin did not cause significative changes of the degree of renal injury,
      compared with either drug given alone.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1980762
TI  - Natural killer (NK) activity of cultured S100 beta-positive T-leukemia cells.
AB  - In order to clarify the function of human S100 beta-positive T-cells, S100 beta
      positive T-leukemia cells (S100 beta TLC) were examined in vitro. S100 beta TLC
      were obtained from the peripheral blood of a patient with S100 beta-positive T
      cell leukemia and enriched by an E-rosetting method. Two dimensional flow
      cytometric analysis indicated that the vast majority of the E-positive fraction
      were S100 beta TLC expressing CD3 and CD8 antigens. Although S100 beta TLC
      expressed CD3 antigen, they were negative for the alpha/beta and gamma/delta T
      cell antigen receptor (TCR) defined by monoclonal antibodies (mabs) WT-31 and
      delta TCS-1, respectively. It was speculated that S100 beta TLC initially
      expressed alpha/beta TCR but lost it during malignant transformation. When S100
      beta TLC were cultured for 24 h, they acquired cytotoxic activity towards various
      NK-sensitive cell lines including K-562, Molt-3 and CEM-CCLF, but did not exhibit
      lysing activity towards NK-resistant cell lines including Raji, Daudi and MT-1.
      Despite the NK-activity of cultured S100 beta TLC, they lacked the morphological
      features of large granular lymphocytes (LGL). S100 beta TLC did not exhibit
      lymphokine-activated killer (LAK) activity. When S100 beta TLC were cocultivated
      with NK-sensitive cells or NK-resistant cells, they selectively bound to NK
      sensitive cells, indicating that they lysed target cells by cell-to-cell contact.
      The finding that S100 beta TLC lacked TCR molecules and their NK activity was not
      inhibited by mabs reactive with the CD3-TCR complex indicated that the CD3-TCR
      complex was not involved in their target recognition.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1980763
TI  - Expression of c-myc and c-fos mRNA in colorectal carcinoma in man.
AB  - Thirty colorectal carcinomas, 1 adenoma of the colon, 1 case of Crohn's disease
      and 13 specimens of non-neoplastic colorectal mucosa were examined for
      qualitative and quantitative expression of the c-myc and c-fos protooncogenes.
      These genes encode nuclear proteins, which are both believed to regulate gene
      transcription. Oncogene expression was evaluated at the mRNA level by in situ
      hybridization and Northern blot analysis. Densitometric analysis of the specific
      bands on Northern blots revealed a highly significant overexpression of c-myc
      mRNA in colorectal carcinomas compared with non-neoplastic tissue (p less than
      0.001). Furthermore, increased expression of c-myc mRNA was found in moderately
      and poorly differentiated carcinomas compared with well differentiated ones. In
      contrast to c-myc, c-fos mRNA expression was significantly lower in carcinomas
      than in non neoplastic tissue (p less than 0.02). Neither, c-myc nor c-fos mRNA
      levels showed a clear-cut correlation with tumor stage. We conclude that c-myc
      mRNA overexpression plays an important role in the progression of colorectal
      carcinomas. In contrast enhanced c-fos mRNA expression may be related to cell
      differentiation, both in tumors and non-neoplastic tissue.

PMID- 1980764
TI  - Expression of several growth factors and their receptor genes in human colon
      carcinomas.
AB  - We have examined the expression of mRNAs for epidermal growth factor (EGF),
      transforming growth factor-alpha (TGF-alpha), EGF receptor (EGFR), PDGF-A chain
      (PDGFA), PDGF-B chain (PDGFB) and PDGF receptor (PDGFR) genes in seven human
      colorectal carcinoma cell lines and 18 human colorectal carcinomas. In surgically
      resected specimens of the 18 colorectal tumors, TGF-alpha, EGFR, PDGFA, PDGFB and
      PDGFR mRNAs were detected at various levels in 15 (83%), 9 (50%), 18 (100%), 8
      (44%) and 12 (67%), respectively. They were also detected in normal tissues.
      Interestingly, EGF mRNA was detected in only five (28%) of the tumors, but not in
      normal mucosa. Expression of EGF was also confirmed immunohistochemically in
      tumor cells. Of the five tumors expressing EGF, four expressed EGFR mRNA and
      showed a tendency to invade veins and lymphatics. All the colorectal carcinoma
      cell lines expressed TGF-alpha mRNA, and five cell lines expressed EGFR mRNA
      simultaneously. Production of TGF-alpha protein by DLD-1 and CoLo320DM cells was
      confirmed by TGF-alpha specific monoclonal antibody binding assay. The
      spontaneous 3H-thymidine uptake by DLD-1 was suppressed by an anti-TGF-alpha
      monoclonal antibody. PDGFA and PDGFB mRNA were also expressed in four cell lines,
      but PDGFR and EGF mRNA was not detected. These results suggest that human
      colorectal carcinomas express multi-loops of growth factors and that TGF-alpha
      produced by tumor cells functions as an autocrine growth factor in human colonic
      carcinoma.

PMID- 1980765
TI  - Morphometry of nucleoli as an indicator for grade of malignancy of bladder
      tumors.
AB  - To establish a new indicator for the classification of human urinary bladder
      cancers, the nucleoli of normal epithelial and neoplastic cells were analyzed,
      using morphometric techniques. By electron microscopy, the nucleolar profiles of
      cells from grade 2 and 3 transitional cell carcinomas were often small and
      irregular. Morphometry showed that the nucleolar volumes, nucleolar/nuclear
      volume ratios, volume densities of various nucleolar components, and the numbers
      of fibrillar centers (FCs) altered significantly with an increase in tumor grade.
      In particular, an increase in FC numbers in the nuclei of higher grade tumors was
      associated with a decrease in individual volume. The number of FCs in intact
      urothelial cells obtained from patients with bladder tumors is significantly
      larger than in the normal urothelial cells. This may be related to the
      multicentric origin of bladder cancers. These results suggest that morphometric
      analysis of nucleoli is useful in evaluating the degree of differentiation and
      invasive capacity of human bladder tumor cells. In particular, the number and
      individual volume of FCs may be an indicator of tumor malignancy.

PMID- 1980766
TI  - [The first impressions of the therapeutic effect of mequitazine (Primalan) in
      allergic patients].
AB  - The therapeutic efficacy of Mequitasin (Primalin) was studied in 31 allergic
      patients--26 patients with allergic rhinitis and 5 patients with skin rashes (4
      patients with acute urticaria and 1 patients with atopic dermatitis). The
      patients were given 1 tablet Primalin twice daily in the course of 14 days. In
      the patients with allergic rhinitis the effect of the treatment was considered
      very good in 42.41% of the patients treated, good--in 50% and lack of effect--in
      7.69% of the patients. In the patients with urticaria and atopic dermatitis the
      results were very good in 60%, good--in 20% and no effect in 20% of the patients
      treated. Side effects were found in 5 patients: in 3 patients--mild up to
      moderate drowsiness, in 1 patient--weakness and 1 patient--dryness in the nose.

PMID- 1980767
TI  - [Hypertension, insulin resistance and diabetes mellitus: pathophysiological
      interactions and therapeutic consequences].
AB  - The pathophysiological connections between insulin resistance, hypertension and
      type 2 diabetes are discussed in this review article. Increased blood pressure
      levels are often found in type 2 diabetic patients long before the diabetes
      itself is diagnosed. By contrast, in type 1 diabetes hypertension is
      predominantly the consequence of diabetic glomerulopathy. Non-pharmacological
      strategies should be favoured in the treatment of hypertension in type 2 diabetic
      patients before specific pharmacological intervention is started.
      Antihypertensive treatment with beta-blocking agents and diuretics is criticized
      by many experts in the field of metabolic disorders, since these drugs induce a
      deterioration of glycaemic control and lipid metabolism in diabetic patients.
      Since calcium channel blockers, ACE inhibitors and alpha 1-specific blocking
      agents have no influence on metabolism, these drugs are recommended for the
      antihypertensive treatment of diabetic patients. Further studies should be
      undertaken to clarify, whether ACE-inhibitors have a specific nephroprotective
      effect. Since most type 2 diabetic patients do not develop diabetic nephropathy,
      a possible nephroprotective effect of ACE inhibitors is only relevant to the
      antihypertensive treatment of type 1 diabetic patients.

PMID- 1980769
TI  - [Octreotide Symposium. 4-5 May 1990, Frankfurt. Proceedings].

PMID- 1980768
TI  - [Antihypertensive drug therapy in diabetes mellitus].

PMID- 1980770
TI  - [Modification of the exocrine pancreas function by octreotide].

PMID- 1980771
TI  - [Effect of somatostatin and octreotide on exocrine pancreas function and
      gastrointestinal motility in fasting conditions].

PMID- 1980772
TI  - [Modification of the motility of stomach, intestine and gallbladder by
      octreotide].

PMID- 1980773
TI  - Somatostatin receptor imaging with 123I-Tyr3-Octreotide.
AB  - Somatostatin receptors have been shown to be present at all main sites of its
      action, such as the anterior pituitary gland, the exocrine and endocrine
      pancreas, the mucosa of the gastrointestinal tract and the central nervous system
      (1, 2). Somatostatin receptors can be measured by two different approaches (3).
      First by direct biochemical techniques, i.e. binding studies on tissue
      homogenates in vitro, which allow precise characterization of the affinities and
      kinetics of these receptors. Secondly, receptors can also be visualized in tissue
      sections with autoradiography. This last method has the advantage of identifying
      histologically the tissues containing these receptors. High numbers of high
      affinity somatostatin receptors have been found on most growth hormone secreting
      pituitary tumors, as well as on many endocrine pancreatic tumors and carcinoids
      (4, 5). These receptors probably form the pathophysiological basis for the
      successful control of hormonal hypersecretion by most of these tumors during
      treatment with octreotide (Sandostatin). Several other human tumor types have
      also been recognized to contain large numbers of high affinity somatostatin
      receptors. All 27 meningiomas investigated contained these receptors, while well
      differentiated glia-derived brain tumors like most oligo-dendrogliomas and (low
      grade) astrocytomas, but not glioblastomas contain somatostatin receptors (6-9).
      Somatostatin receptors have also been found on 20-40% of human breast cancers
      (10).

PMID- 1980774
TI  - [Clinical applications of octreotide in gastro-entero-pancreatic (GEP) tumors].

PMID- 1980775
TI  - [Treatment of therapy-resistant acromegaly using Sandostatin].

PMID- 1980776
TI  - [Drug treatment of acute esophageal varices hemorrhage using vasoactive
      substances (somatostatin and octreotide)].

PMID- 1980777
TI  - [Possibilities of application of octreotide in surgery. 1)Treatment of
      gastrointestinal fistulas; 2)Prevention of complications in pancreatic surgery].

PMID- 1980778
TI  - Future medical prospects for Sandostatin.
AB  - Because of its widespread distribution within the nervous system and the gastro
      enteropancreatic (GEP) system and its diverse physiological inhibitory actions on
      various gastrointestinal functions, including endocrine and exocrine secretion,
      motility, liver and splanchnic blood flow and absorption, native somatostatin has
      been viewed as a possible therapy for many diseases. However, its short duration
      of action and consequent limited clinical usefulness have been overcome with the
      availability of Sandostatin, a long-acting, synthetic octapeptide analogue of the
      naturally occurring hormone. Sandostatin represents a significant advance in the
      treatment of GH and TSH secreting pituitary tumours and GEP endocrine tumours
      (carcinoid tumour, VIPoma, glucagonoma, insulinoma, and gastrinoma). Preclinical
      in vitro and animal studies have shown the antineoplastic activity of the
      compound. Moreover, because of a possible direct effect on somatostatin receptor
      positive endocrine tumour cells and indirect effect whereby Sandostatin lowers
      GH, IGF-1 and numerous gastrointestinal peptides, Sandostatin may prove useful as
      an adjunctive therapy in cancer patients. In vivo labelling of somatostatin
      receptor-positive tumours with radiolabelled somatostatin analogues now allows
      localisation of such tumours and their metastases. Moreover, targeted irradiation
      of these tumours by beta particle emitting isotopes attached to such somatostatin
      analogues may become possible. The use of Sandostatin in acute oesophageal
      variceal bleeding, pancreatic pseudocysts, gastrointestinal and pancreatic
      external fistulae, short bowel syndrome, dumping syndrome and AIDS-related
      refractory hypersecretory diarrhea has provided encouraging results. Preliminary
      reports indicate efficacy of Sandostatin in psoriasis, autonomic neuropathy
      (postprandial and orthostatic hypotension) and its ability to reduce height
      velocity in tall adolescents. The ultimate role of Sandostatin as a therapeutic
      agent in these disorders is being explored in prospective clinical
      trials.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1980779
TI  - [Determination of the activity of gamma-glutamyltransferase in severely hemolytic
      blood samples].

PMID- 1980780
TI  - [Magnetic resonance imaging of the foot].
AB  - We evaluated the diagnostic value of magnetic resonance imaging retrospectively
      in 72 patients (76 examinations). 10 examinations were normal, 2 showed normal
      variants, 21 inflammatory disease, 2 osteoarthritis, 7 neoplasia, 21 traumatic
      changes, 3 pathology in systemic disease, 5 avascular necrosis, 5 iatrogenic
      changes. When considering the original reports, accuracy had been 72.4%,
      sensitivity 75%, specificity 62.5%. After review of the hard copies several
      diagnoses were revised, improving the values to 86.6%, 84.4% and 100%
      respectively. Compared with other radiologic examinations the main advantages of
      magnetic resonance imaging were its high contrast resolution and the free choice
      of the imaging plane. The main disadvantages were the reduced spatial resolution
      compared to CT and the significantly worse definition of calcification and
      cortical bone. In conjunction with other radiologic and clinical examinations
      magnetic resonance imaging played an important role in the examination of
      avascular necrosis, inflammation, tendon pathology and neoplasia.

PMID- 1980781
TI  - [Synthesis and analgesic activity of 1-substituted derivatives of 4
      methoxycarbonyl-4-N-propionylanilinepiperidine].
AB  - In this paper, the synthesis and analgesic activities of a series of 1
      substituted derivatives of N-[1-(2-phenylethyl)-4-methoxycarbonyl-4-piperidinyl]
      N-propionylanil ine (4-methoxycarbonyl fentanyl) are reported. Preliminary
      pharmacological results showed that most compounds in this series exhibited
      typical morphine-like action and that replacement of beta-phenyl group in the 1
      position of piperidine ring of 4-methoxycarbonyl fentanyl by some substituents
      e.g., some substituted vinyl groups, heterocyclic (or alcyclic) radicals, alkyl
      groups or N-methyl-anilino groups, can keep strong analgesic activity.
      Especially, some substituted vinyl groups were found to be effective groups which
      could replace 1-beta-phenyl group of 4-methoxycarbonyl fentanyl. Compounds N-[1
      (3, 4-dimethyl-3-pentenyl)-4-methoxycarbonyl-4-piperidinyl]-N-
      propionylaniline(1321) and N-[1-(4-methyl-3-pentenyl)-4-methoxycarbonyl-4
      piperidinyl]-N- propionylaniline(1302) exhibited higher analgesic activity than
      that of 4-methoxycarbonyl fentanyl.

PMID- 1980782
TI  - [Stripping voltammetric determination of perphenazine and some antipsychotic
      drugs at carbon paste electrodes].
AB  - A sensitive electrochemical method for the determination of four drugs:
      perphenazine, fluphenazine chlorpromazine and trifluperazine is reported. These
      compounds exhibited accumulation at carbon paste electrodes in an open circuit.
      Differential pulse voltammetric determination gave linear calibration curves in
      the range of 0.02-1 microgram/ml. Detection limits found were 5-7 ng/ml. The
      drugs in tablets and body fluids were determined directly without separation. The
      preconcentration mechanism and determination conditions in a new kind of carbon
      paste piston electrode were investigated. Adsorption and extraction played
      important roles in accumulation process and the ratio of these two parts was
      measured by chronocoulometry.

PMID- 1980783
TI  - Investigation of 2-hydroxylamino-5-ethyl-5-sec-pentylbarbituric acid for
      anxyolitic action.
AB  - Comparative tests were performed on male albino rats to study the activity of the
      original hydroxylamine barbiturate HB-7, with phenobarbital (PhB) and
      pentobarbital (PB) using the conflict situation test (after Vogel et al., 1971)
      with thirsty rats (deprived of water for 48 hours). The three barbiturates
      studied (HB-7, PhB and PB) were administered intraperitoneally in four doses (5,
      10, 15 and 20 mg/kg). Two parameters were registered: number of punished
      responses (electrical shocks punishing attempts to drink) and the number of non
      punished responses (approaching the drinking tube) for the 5-min period of
      observation. In a second group of experiments the same test was used to study the
      effect of picrotoxin and of its combinations with the effective doses of HB-7,
      PhB and PB. The three barbiturates tested were found to have an anxiolytic
      effect, i.e. to increase the number of attempts to drink water, in the higher
      doses used. Picrotoxin causes a decrease in the number of punished responses
      (anxiomimetic effect). When HB-7, PhB and PB are combined with picrotoxin, the
      latter eliminates their anxiolytic action. The conclusion reached is that the
      anxiolytic action of the barbiturates tested is probably connected with an effect
      on the GABA-ergic transmitter system in the central nervous system.

PMID- 1980784
TI  - Effects of somatostatin and motilin on the motor and myoelectrical activity of
      the canine stomach and small intestine in vivo.
AB  - The experiments were performed on six starved dogs with chronic fistula in the
      stomach and small intestine and with chronically implanted electrodes on the
      smooth-muscle wall of these organs. Motilin (15-25 ng/kg i.v.) induced fastedtype
      peristaltic contractions accompanied by migrating myoelectrical spike activity in
      the stomach and small intestine. Somatostatin (0.5-2 micrograms/kg i.v.)
      inhibited the spontaneous contractile activity and the spike potentials in both
      organs. The antagonistic effect of somatostatin on the spontaneous and motilin
      induced contractions resembled the effect of atropine and probably resulted from
      the decreased acetylcholine release in the cholinergic neurons.

PMID- 1980785
TI  - Neuroleptic malignant syndrome: a subtype of lethal catatonia?

PMID- 1980787
TI  - Early appearance of tyrosine hydroxylase immunoreactive cells in the
      mesencephalon of mouse embryos.
AB  - The development of mesencephalic catecholaminergic neurons in the embryonic and
      fetal mouse was analysed in tissues fixed with 5% acrolein using polyclonal
      rabbit antibodies against tyrosine hydroxylase (TH), the first enzyme in
      catecholamine synthesis. The first TH positive cells were identified as early as
      day 8.5-9 of gestation and some expressed TH while apparently still migrating
      from the proliferative layer. The number of catecholamine cells increased
      dramatically by embryonic day 9.5-10; at gestation days 10.5-11 numerous TH
      positive cells bearing many neurites were localized in the ventral part of the
      mesencephalon but they were not yet separated into two different groups (A9 and
      A10). After 13 days of gestation two separate catecholaminergic groups could be
      visualized, although many TH positive cells with long neurites (putative
      dopaminergic neurons) could still be seen at the edges of the ventricle, and
      appeared to be moving towards the ventral mesencephalon. On the basis of these
      results the possibility that catecholamine cells that are produced early during
      the development of the midbrain may have neurotrophic and/or morphogenetic roles
      is discussed.

PMID- 1980786
TI  - Development of neurotransmitter systems in the mouse embryo following acute
      ethanol exposure: a histological and immunocytochemical study.
AB  - Acute maternal ethanol administration to C57B1/6J mice on gestational day 7 (GD7)
      results in facial and brain abnormalities similar to those reported in human
      fetal alcohol syndrome (FAS). Using this model, we assessed the damage to brain
      structures using histological methods and changes in developing neurotransmitter
      systems with immunocytochemistry. Cholinergic neurons in the forebrain were
      stained with a monoclonal antibody to choline acetyltransferase (ChAT).
      Catecholaminergic neurons in the midbrain and serotoninergic neurons in the
      hindbrain were stained with polyclonal antisera to tyrosine hydroxylase (TH) and
      serotonin (5-HT), respectively. Forebrain deficiencies, including loss of midline
      structures (olfactory bulbs, midline septation, medial septal area) and deficits
      in lateral and dorsal regions (neostriatum and cerebral cortex) were found in
      both GD14 embryos and GD18 fetuses. In severely affected offspring, complete loss
      of the septal region resulted in conjoined lateral ventricles and a reduction in
      the thickness of the ventricular zone surrounding the single ventricle, as well
      as a severe loss of ChAT neurons which would normally be located in this
      territory. However, no consistent changes were seen in the distribution or size
      of TH or 5-HT neuronal cell groups in the midbrain and hindbrain. These
      differences in effects on specific neurotransmitter systems reflect the fact that
      the forebrain is most severely affected by early ethanol administration, whereas
      the hindbrain is relatively spared. Such differential effects could produce an
      imbalance in developing neurotransmitter systems in the embryonic and fetal
      brain, which could explain some of the functional deficits observed in children
      with FAS.

PMID- 1980788
TI  - [Surgical management of shoulderblade fractures].
AB  - Fractures of the scapula are a domain of conservative therapy. In the majority of
      cases early restoration of function produces good results. Nevertheless there are
      types of fractures which should be reduced in open procedures and treated by an
      osteosynthetic method stable enough to ensure early mobilisation. A report of 5
      patients is presented, 2 of whom showing severe, 1 light and the remaining 2 no
      concomitant injuries. Indications, access, choice of procedure and results are
      described.

PMID- 1980789
TI  - [Temporary extra-articular Bosworth' fixation in complete shoulder joint
      separation. Follow-up results of 41 surgically treated patients].
AB  - 41 patients were reviewed who suffered from complete separation of the
      acromioclavicular joint which was operated on with an extraarticular clavicular
      coracoid fixation by means of a Bosworth screw. In 82% of the cases a subjective
      and functionally good to excellent result was found. Only one patient complained
      about difficulties in managing daily life. One patient showed a subluxation of
      the acromioclavicular joint in X-ray with 10kp extension, all other patients
      demonstrated stabile relations of the ligaments. The coraco-clavicular
      calcifications of the ligaments increased with the number of months after
      operation without a negative influence on functions. An operation without much
      irritation and in a short period of time, the early beginning of functional
      therapy and the impressive results of the review show that the technique after
      Bosworth appears superior to other comparable procedures.

PMID- 1980790
TI  - [Juxta-articular osteoid osteoma--Image morphology and diagnosis].
AB  - Juxta-articular osteoid osteomas as a cause of persistent pain of the shoulder,
      elbow and knee are presented basing on three own observations and a review of the
      literature. The sequence of the imaging examinations is equivalent to the osteoid
      osteomas in other localisations. CT permits a clear presentation of the nidus in
      the complex juxta-articular anatomy. Juxta-articular osteoid osteomas often show
      an absent or small perifocal osteosclerosis, whereas a laminar periosteal
      reaction was seen in all own cases.

PMID- 1980791
TI  - [Femoral fractures in osteodystrophy deformans (Paget's disease). Treatment
      results].
AB  - Between 1958 and 1986 21 fractures of the femur in Osteodystrophia deformans
      (Paget's disease) were treated at the accident hospital Meidling; of these 13
      patients were female and 8 of male. The average age was 73.4 years. In two cases
      the basic illness was known, in 19 cases the fracture was the first manifestation
      of the illness. In 7 cases a polyostotic manifestation was evident. The fractures
      were localized as follows: 7 in the proximal, 7 in the middle, 1 in the distal
      third of the shaft, 5 subtrochanteric, 1 supracondylar. Apart from one
      subtrochanteric torsion fracture, all were flexure fractures without splinters.
      19 fractures were stabilized by an operation: 17 by intramedullary nailing (with
      cerclage), 1 steep plate, 1 Ender nail. One case was treated by an extension,
      whereas in one case no operation was performed. The following complications were
      observed: one fracture of the steep plate, one delayed healing of the fracture
      after intramedullary nailing. No infections could be observed. In general,
      healing of the fracture in Osteodystrophia deformans does not seem to be delayed.
      The different possibilities of intramedullary nailing of the femur - possibly
      together with osteotomies to eliminate curvature - can be recommended for
      fractures in Osteodystrophia deformans.

PMID- 1980792
TI  - [Alternative treatment methods in complex fractures and fracture-dislocations of
      the anterior tarsus].
AB  - Obtaining and maintaining an anatomic reduction are the keystones in the
      treatment of severe midtarsal injuries to avoid long-term disability. The use of
      the small external fixator or the minidistractor allows an indirect reduction
      with careful management of the soft tissues. By leaving the external fixation for
      at least 8 weeks the important length of the medial and lateral longitudinal arch
      can be maintained. Further advantages are the postoperative observation of the
      soft tissues and circulation without cast immobilisation.

PMID- 1980793
TI  - [The classification of osteomyelitis].
AB  - The article presents the classification of osteomyelitis commonly used by us,
      where the four typical characteristics are described by means of figure codes:
      Cause of infection (A), duration of infection (D), bone findings (K) and soft
      part findings (W) at the beginning of osteomyelitis therapy. The characteristics
      are represented by different figure combinations, single-digit figures being
      sufficient for description, whereas multiple-digit figures (maximum: 4) are
      required for more exact typing. Each characteristic is coded separate from the
      others, thus making it possible to communicate individual characteristics. --Our
      findings are always based on simple measurement data. Bone defects are calculated
      approximately spatially by means of transformation. The concepts and definitions
      are explained. --Classification is intended to be helpful when compiling
      differentiated statistics and to enable a comparison in case of diagnostic or
      therapeutic studies on osteomyelitis.

PMID- 1980794
TI  - [Closed tendon injuries of the hand].
AB  - Cases of subcutaneous tendon ruptures of the hand were compiled over a period of
      10 years; the lesions were all traumatic rather than due to degenerative illness.
      The 914 injuries fall into two categories: 867 extensor and 47 flexor tendon
      ruptures. The localisation of the lesions is most often distal. The extensor
      tendon lesion is accompanied more often by a ruptured bony fragment; the distal
      flexor tendon is mostly torn-off bony fragment. The extensor tendon ruptures can
      be subdivided as follows: distal injuries of the extensor aponeurosis in the DIP
      joint (751 cases), IP joint (31), tractus intermedius (27), ext. carpi radialis
      longus (5) and brevis (1), ext. carpi ulnaris (6); proximal ruptures of the ext.
      pollicis longus (42), ext. digitorum communis II and indicis (1 each) and ext.
      carpi radialis longus and brevis (1 each). The flexor tendon lesions are as
      follows: distal injuries to flex. digitorum profundus (32 cases), flex. pollicis
      longus (9), and the opponens pollicis, which is classified under this heading
      (2). Proximal lesions to flex. pollicis longus (2) and flex. digitorum profundus
      and superficialis (1 each).

PMID- 1980795
TI  - [The significance of acalculous cholecystitis in prolonged respiratory failure in
      severely burned patients].
AB  - Acalculous cholecystitis is a very rare complication in severely burned patients.
      The correlation between acalculous cholecystitis and the development of a
      protracted pulmonary failure is demonstrated in 5 patients. Marked improvement of
      pulmonary function was achieved by cholecystectomy in all patients.

PMID- 1980796
TI  - [The meniscus suture. Results of a clinical and sonographic follow-up study].
AB  - The goal of our clinical and ultrasonographic study was to evaluate the results
      of the patients who underwent meniscal suture between June 1983 and December 1987
      in our clinic. 41 patients (82%) were examined by the author, the mean follow-up
      time was 40 months. The mean Lysholm score rate was 93.4 points. 72.9% were able
      to return to their former sports level. 3 patients were suggested to have
      recurrence, but this could not be proven by arthroscopic and ultrasonographic
      means. High grade congruency of clinical and sonographic examination was obvious
      as it was in the literature. The meniscal suture healed in 92.5% so we recommend
      the procedure if ever possible.

PMID- 1980797
TI  - [Self-detaching incision foil].

PMID- 1980798
TI  - [Requirements for the physician's referral letter: is it necessary to instruct
      the colleague who takes over treatment?].

PMID- 1980799
TI  - Ultrastructural study of the interaction between eosinophilic granulocytes and
      third and fourth stage larvae of Onchocerca volvulus.
AB  - The interaction in vitro between eosinophil effector cells and third and fourth
      stage larvae of Onchocerca volvulus was studied by electron microscopy. The
      morphological observations demonstrated different mechanisms of attack of
      eosinophil cells that are dependent upon the time of incubation. Rapid adherence
      to the cuticle of the target, flattening, secretion of granule contents, vacuole
      formation and, finally, complete degranulation of the eosinophils were seen after
      incubation with third stage larvae and moulting stages. Alterations of the
      epicuticular and cuticular structures could be found near the attachment site of
      the cells. The eosinophils, however, showed no interactions with fourth stage
      larvae of this filarial parasite.

PMID- 1980800
TI  - Malaria and its treatment in rural villages of Aboh Mbaise, Imo State, Nigeria.
AB  - We examined the malaria situation among 489 children under 5 years of age in the
      rural villages of Aboh Mbaise, Nigeria, using a combination of a standard
      questionnaire technique and laboratory diagnosis to confirm clinical
      observations. The results show a high prevalence rate of 52.8% for Plasmodium
      falciparum in this area. The geometric mean parasite density (GMPD) was
      19,361.4/mm3. The proportion of children with fever and/or parasitaemia was not
      related to age, although the numbers in the febrile group appeared to increase
      with age. Using 37.5 degrees C as the threshold for fever, 48.7% of the heavily
      infected group (more than 1000/mm3) were afebrile while 51.3% were febrile. High
      grade temperatures above 38 degrees C were associated with high parasitaemia
      above 10,000 parasites/mm3. Of the 911 children who died in the area within the
      last five years, 22.4% died of fever of unknown origin, 39.7% from malaria, 22.5%
      from convulsion, 10.5% from diarrhoea and 4.6% from cough. Chloroquine is the
      drug of choice for the treatment of malaria and there were many cases of drug
      abuse, and use of sub-curative doses prescribed by non-medically qualified staff.

PMID- 1980802
TI  - Effect of trypanosome infection, control of parasitaemia and control of anaemia
      development on productivity of N'Dama cattle.
AB  - One hundred and forty six calving interval records were built up from 64 N'Dama
      cows maintained for 3.5 years under a high natural tsetse challenge in Zaire.
      Matching health and performance data were recorded monthly to allow simultaneous
      evaluation of the effects of different criteria of trypanotolerance represented
      by time detected parasitaemic, parasitaemia score and packed red cell volume
      percent (PCV) on reproductive performance, calf weaning weight and cow
      productivity. Control of development of anaemia, measured by PCV value during
      trypanosome infection, had the major effect on all three performance traits. The
      repeatability of this criterion (0.33) was almost equal to that of calf weaning
      weight, indicating PCV measurement might be suitable for identification of more
      trypanotolerant animals. Simultaneous evaluation of the relative effects of
      control of development of anaemia in both the pre-weaner calf and its dam, on
      calf performance, suggested that its measurement in an animal might be feasible
      at an early post-weaner stage. Guidelines for work to develop practical field
      tests for trypanotolerance involving post-weaners maintained for varying lengths
      of time in high natural challenge situations are suggested.

PMID- 1980801
TI  - Mixed Schistosoma haematobium and S. mansoni infection: effect of different
      treatments on the serum level of circulating anodic antigen (CAA).
AB  - In this study, levels of circulating anodic antigen (CAA) in serum were
      investigated after differential treatment of 160 Sudanese patients with mixed
      Schistosoma haematobium and S. mansoni infections. The patients were randomly
      divided into four groups, which were treated with metrifonate (two doses of 10
      mg/kg bodyweight), oxamniquine (60 mg/kg), praziquantel (40 mg/kg), or a
      multivitamin preparation, respectively. Serum, stool and urine samples were taken
      prior to treatment as well as one month and five months after chemotherapy.
      Before chemotherapy CAA levels were similar in the four groups. Antigenemia
      remained unchanged in the control group. In patients treated with praziquantel or
      oxamniquine the concentration of CAA decreased to a similar extent. However,
      whereas in the praziquantel group absence of CAA was already observed one month
      after treatment, clearing of CAA from the circulation seemed to take longer in
      patients treated with oxamniquine. Treatment with metrifonate did not result in a
      reduction of the CAA titres.

PMID- 1980803
TI  - Evaluation of a field test for trypanotolerance in young N'Dama cattle.
AB  - In three separate tests in 1987, 1988 and 1989, a total of 436 one-year-old
      N'Dama cattle were maintained for 12, 18 and 24 weeks under a medium natural
      tsetse-trypanosome challenge in Gabon, Central Africa. Matching health and
      performance data were recorded on 4, 10 and 13 occasions respectively, to allow
      simultaneous evaluation of the effect of different criteria of trypanotolerance
      on animal performance. Under trypanosome prevalences of 25, 31 and 9%,
      respectively, ability to control the development of anaemia had a very major
      effect on daily weight gain, four times that of the ability to control
      parasitaemia, while previous exposure to trypanosome infection from birth to one
      year had no effect. Anaemia control, measured by average packed red cell volume
      percent (PCV) over the test period or by lowest PCV reached, was more closely
      associated with animal performance than when measured by average PCV when
      detected as parasitaemic. Above average PCV values in the first two measures
      resulted in a 44% to 48% superior daily weight gain over below average PCV
      values. PCV post-test recovery was shown to be rapid following a single
      trypanocidal drug treatment. In practice, it appeared that a suitable field test
      would be where natural infection could be effected as early in the test as
      possible and anaemia control measurements carried out over 6 weeks of detected
      parasitaemia. A field test would become even more feasible if satisfactory
      correlation could be obtained between the results of natural infection and those
      of an experimental alternative.

PMID- 1980804
TI  - Resistance to benzimidazoles in Haemonchus contortus of sheep in Tanzania.
AB  - This study was undertaken to establish whether resistance to benzimidazole
      anthelmintics was present in gastrointestinal nematodes of sheep and goats at the
      university farm of Sokoine University of Agriculture, Morogoro, Tanzania. Groups
      of lambs were treated with albendazole at 3.8 mg/kg (recommended dose rate), 5.6
      mg/kg and 10.0 mg/kg and a fourth group was untreated. Seven days after
      treatment, faecal egg count reductions (FECR) were found to be 94.3%, 97.6% and
      99.3% and 14 days after treatment FECR of the same groups were 83.0%, 81.3% and
      99.6%, respectively. Larval cultures indicated that only H. contortus were
      present in post-treatment samples. This strain of H. contortus, (DASP) and
      another strain of H. contortus (MKATA), considered susceptible to anthelmintics,
      were used in an experimental in vivo study and for an in vitro egg hatch assay.
      Treatment with fenbendazole at the recommended dose of groups of lambs infected
      with either strains showed no reduction in the DASP strain and a 70.5% reduction
      in the MKATA strain. The in vitro egg hatch assay established a significant
      difference (p less than 0.05) in hatchability of eggs of the two strains. The
      development of the high level of resistance to fenbendazole in the DASP strain is
      related to the history of anthelmintic usage and management of sheep and goats at
      the university farm.

PMID- 1980805
TI  - Acquired resistance in goats following a single primary Schistosoma bovis
      infection.
AB  - The course of Schistosoma bovis infection was monitored in West African Dwarf
      Goats over a 34-week period following primary, experimental exposure (3000
      cercariae/animal) and over a 17-week period following challenge exposure (2500
      cercariae/animal) of goats harbouring 17-week old primary infection. For
      comparison, groups of challenge control and parasite-free control animals were
      monitored. Maximal egg excretion observed from week 8 to 12 following primary
      infection was accompanied by reduced weight gain, marked anaemia,
      hypoalbuminaemia and eosinophilia. These changes gradually diminished in parallel
      with decreasing egg excretion from week 14 onwards. Challenge infection induced
      neither additional egg excretion nor adverse effects in primary-infected animals.
      This was in contrast to challenge control animals which revealed the typical
      course of experimental schistosome infection including a peak of egg excretion,
      weight gain affection, and associated clinico-pathological changes. It was
      concluded that goats are capable of mounting an effective regulatory response to
      single primary S. bovis infection as well as to superimposed homologous challenge
      infection. Further elucidation of the regulatory response to S. bovis infection
      in goats are needed in order to determine its possible immunological background
      and epidemiological impact.

PMID- 1980806
TI  - Subspecific kDNA probes for major clones of Trypanosoma cruzi.

PMID- 1980807
TI  - Salivary gland infection: a sex-linked recessive character in tsetse?
AB  - Male tsetse, when infected in the laboratory with trypanosomes of the subgenus
      Trypanozoon, usually produce greater salivary gland infection rates than females
      of the same species. We show that a single sex-linked gene model can be fitted to
      most recently published data for salivary gland infection rates in tsetse. The
      maturation of Trypanosoma congolense infections is shown to be independent of fly
      sex. The possible effects of genetic control of maturation of Trypanozoon
      infections in tsetse populations on the transmission of sleeping sickness are
      considered.

PMID- 1980808
TI  - Recovery of tryptophan in peptides and proteins by high-temperature and short
      term acid hydrolysis in the presence of phenol.
AB  - The addition of 3% (w/v) phenol to 6 M HCl largely prevented the destruction of
      tryptophan during rapid hydrolysis of peptides and proteins at 166 degrees C for
      25 min or at 145 degrees C for 4 h. This hydrolysis procedure was advantageous
      for amino acid microanalysis using conventional high-performance liquid
      chromatography with a precolumn derivatization technique. The recovery of
      tryptophan from proteins was at least 80%. The addition of phenol also improved
      the recovery of methionine and carboxymethylcysteine. The amount of tryptophan in
      proteins electroblotted onto a polyvinylidene difluoride membrane was determined
      by this method.

PMID- 1980809
TI  - [Gastroduodenal incretory cells in duodenal ulcer with different levels of
      gastric secretion].
AB  - Immunomorphological PAP method was used in 20 patients with duodenum ulcer and in
      10 control individuals to study gastrin (G)-, somatostatin (D)- and calcitonin
      gene-related peptide (CGRP) cells in biopsies of the stomach and duodenum. The
      gastrin and pepsinogen level in the blood, basal and acid production stimulated
      by pentagastrin were also studied. All patients are subdivided into two groups by
      their acid production: those with hypersecretion and those with normal secretion.
      The group with hypersecretion was not homogeneous: some patients had deficiency
      of D-cells (sometimes in combination with G-cell hyperplasia) and others had a
      relative and absolute decrease of the number of CGRP cells in combination with
      foci of parietal cells in pylorus. These patients showed a tendency to the
      hypergastrinemia and significant hyperpepsinogenemia I in the blood. Stomach
      hyperplasia in the duodenum, multiple duodenal ulcers, erosive gastroduodenitis
      and ulcers in close relatives occurred more frequently in these patients. G- and
      CGRP cells are found to be similar in the form and localization. It is not
      excluded that G-cell contains, apart from gastrin 1-17, calcitonin-gene related
      peptide.

PMID- 1980810
TI  - [The morphological characteristics of endocrine-cell cancers of the large
      intestine].
AB  - Histological variants of colon carcinoma depending upon the quantity of endocrine
      cells are distinguished on the basis of 66 malignant epithelial colon tumours
      morphological investigation. Special emphasis was made on the characteristics of
      the endocrine cell carcinoma, combined tumours with a combination of glandular
      and endocrine components, and amphicrin neoplasms. A trabecular-glandular variant
      of endocrine cell carcinoma is found to be predominant in the colon. The criteria
      are suggested for the identification of endocrine-cell tumours.

PMID- 1980811
TI  - Activity of dipeptidyl peptidase II and dipeptidyl peptidase IV in human gingiva
      with chronic marginal periodontitis.
AB  - The activity of DPP II was higher in gingiva from patients with periodontitis,
      but the activity of DPP IV, post-proline cleaving enzyme and collagenase-like
      peptidase was not significantly higher than that of the control group. As DPP II
      activity is known to be altered in immunological diseases, these findings may
      suggest some role for DPP II in the pathogenesis of chronic marginal
      periodontitis.

PMID- 1980812
TI  - Analysis of B complex polymorphism in Rous sarcoma progressor and regressor
      chickens with B-G, B-F, and B-L beta probes.
AB  - Molecular polymorphism of the B complex was studied in serologically defined B19
      haplotypes by use of class I, class II, and class IV probes in Southern blot
      experiments in chickens. All chickens studied shared identical class IV
      restriction patterns. In contrast, class I and class II probes revealed six and
      five subtypes of B19 haplotype, respectively. These subtypes may be resolved in
      three homozygous genotypes and their corresponding heterozygous combinations.
      Previous genetic selection allowed us to distinguish two subpopulations in these
      B19 chickens with regard to the fate of Rous sarcoma virus (RSV)-induced tumors.
      Molecular genotyping was applied to B19 chickens challenged with RSV in order to
      determine whether there is a correlation between one of the molecularly defined
      subtypes and the progressor/regressor phenotypes of the chickens. None of the
      molecularly defined subtypes correlated with the progressor or regressor
      phenotype of the challenged birds.

PMID- 1980814
TI  - International Minisymposium on Food Technology in the Year 2000. Helsinki,
      November 14, 1989. Proceedings.

PMID- 1980813
TI  - DNA damage and repair in human tissues. A symposium. October 1-4, 1989, Upton,
      New York. Proceedings.

PMID- 1980815
TI  - Postnatal ontogeny of gamma glutamyltranspeptidase activity of pancreas in
      essential fatty acid deficient rats treated with nitrosomethylurea.
AB  - The effect of essential fatty acid deficiency and nitrosomethylurea treatment on
      postnatal levels of pancreatic gamma-glutamyltranspeptidase was studied. A
      significant increase of gamma-glutamyltranspeptidase activity and changes in
      fatty acid composition were observed in essential fatty acid deficient rats, from
      the 14th day of life on. Pancreatic gamma-glutamyltranspeptidase of
      nitrosomethylurea injected rats in essential fatty acid deficiency and controls
      was significantly diminished at the 30th day, with no significant differences in
      both nutritional conditions. The results indicated: 1. Concomitant changes in
      gamma-glutamyltranspeptidase activity and fatty acid composition of rat pancreas
      in essential fatty acid deficiency, 2. A significant reduction of pancreatic
      gamma-glutamyltranspeptidase activity following a single intraperitoneal
      injection of nitrosomethylurea at day one of life and 3. No interacting effects
      of essential fatty acid deficiency and nitrosomethylurea on gamma
      glutamyltranspeptidase activity of rat pancreas.

PMID- 1980816
TI  - Lipoprotein and hepatic lipase gene variants in coronary atherosclerosis.
AB  - Lipoprotein lipase is the rate determining enzyme for the removal of triglyceride
      rich lipoproteins from the blood stream. We examined whether genetic variation at
      the lipoprotein lipase gene locus is related to the occurrence of premature
      coronary artery disease. Two restriction fragment length polymorphisms, revealed
      by the enzymes HindIII and PvuII, demonstrated alleles designated H1 (17.5 kb),
      H2 (8.7 kb), P1 (7.0 kb), P2 (4.4 kb and 2.5 kb) respectively. These were studied
      in 70 Caucasian subjects with severe coronary atherosclerosis in comparison with
      122 Caucasian healthy controls. The allelic frequencies for cases and controls
      were respectively: H2 0.770, 0.579 (P less than 0.001); P2 0.575, 0.554 (P NS).
      The allelic frequencies of the HindIII and BglII polymorphic sites at the hepatic
      lipase gene locus were also studied in the same groups of subjects. These showed
      no differences between cases and controls. We conclude that DNA variation at or
      adjacent to the lipoprotein lipase gene may contain genetic determinants for the
      occurrence of premature coronary artery disease.

PMID- 1980817
TI  - Molecular properties of the histamine H2-receptor. Covalent inhibition by
      tetraamine disulfides.
AB  - A series of tetraamine disulfides related to benextramine (an alpha
      adrenoreceptor and H2-receptor antagonist) in which the distance between the
      inner and the outer nitrogens were changed from five to nine methylenes has been
      studied. Both effects of the displacement of the disulfide bridge by two
      methylenes and those of the progressive removal of two of the four nitrogens on
      the pharmacological profile have been assessed. Peak potency appeared to be
      associated with eight methylenes between the inner and the outer nitrogens and to
      four cationic charges as in the most active analogue 4 which was also
      investigated to assess its receptor specificity towards histamine H1 and
      muscarinic M2 and M3 receptors. The finding that the carbon analogue 11 (two
      methylenes for the disulfide bridge) was devoid of activity is consistent with
      the hypothesis that histamine H2-receptor inhibition is the result of a covalent
      bond formation by a way of a disulfide-thiol interchange reaction between the
      disulfide moiety of tetraamine disulfides and a receptor thiol group. However,
      the possibility that tetraamine disulfides may not act at the H2-receptor but
      beyond the receptor cannot be excluded.

PMID- 1980818
TI  - [Quantitative determination of strychnine and brucine in semen Strychni and its
      preparations by gas chromatography].
AB  - Contents of strychnine and brucine in dry seeds of Strychnos nux-vomica and its
      preparations were determined by gas chromatography. The determination conditions
      were:support Gas Chrom Q; liquid phase 3% OV-101; stainless steel column 0.5 m x
      3 mm; column temperature 265 degrees C; FID detector.

PMID- 1980819
TI  - [Simultaneous determination of brucine and strychnine in semen Strychni by dual
      wavelength spectrophotometry and studies on processing principles of semen
      Strychni].
AB  - The paper reports the experimental result of the simultaneous quantitative
      determination of strychnine (ST) and brucine(BR) in Semen Strychni by dual
      wavelength spectrophotometry. The result shows that there are some deviations in
      the official method, because the wavelength combination might not have been
      chosen rightly and the correct coefficient is inconsistent with the facts. We
      have made a study of the thermal stability of ST and BR, too. On this basis a
      baking principle for Semen strychni is spelt out.

PMID- 1980820
TI  - Changing concepts in HIV infection: challenges for the 1990s.

PMID- 1980821
TI  - Trends in survival of Danish AIDS patients from 1981 to 1989.
AB  - Length of survival was analysed in relation to year of diagnosis, AIDS-indicative
      disease, age, risk behaviour, zidovudine therapy, and CD4 cell count and serum
      immunoglobulin (Ig) levels at the time of diagnosis in a group of 231 consecutive
      adult Danish AIDS patients reported before 1 January 1988. The cumulative
      survival rate was 53% (95% confidence interval 47-59%) at 1 year, 29% (22-36%) at
      2 years and 18% (10-26%) at 3 years. Length of survival increased significantly
      (P less than 0.001) over time for patients who were initially diagnosed with
      Pneumocystis carinii pneumonia (PCP), 17% (3-31%) at 2 years prior to 1986, 32%
      (16-49%) in 1986 and 52% (34-69%) in 1987, whereas survival remained stable for
      patients with other AIDS-indicative diseases. Survival was similar for patients
      who were diagnosed with Kaposi's sarcoma alone and PCP alone. Independent
      predictors of a shortened survival were a CD4 cell count less than 200 x 10(6)/l,
      a serum IgA level greater than 4 g/l, and an initial diagnosis with opportunistic
      infections other than PCP. In addition, the multivariate analysis suggested an
      improved survival in recent years for patients diagnosed with PCP, independent of
      other factors examined. We conclude that length of survival in AIDS patients is
      highly variable. Determinants of progression include CD4 cell count, serum IgA
      level, and presenting disease. Survival has increased markedly for patients with
      PCP and median survival now exceeds 24 months.

PMID- 1980822
TI  - The proliferative response of peripheral blood mononuclear cells to
      streptokinase. A study of patients receiving a single intravenous infusion of
      purified streptokinase.
AB  - In vitro proliferative PBM responses were investigated for 26 patients with and 5
      patients without acute myocardial infarction. All patients were initially treated
      with streptokinase (1.5 MIU infused for 1 hour). Five weeks after the disease
      increased responses to streptokinase, PPD and PHA were seen; but only for
      streptokinase had original nonresponders become responders (7 out of 14
      nonresponders). The increased responsiveness to streptokinase could be detected
      five days after antigen infusion, and CD-2 positive cells constituted a major
      part of the proliferating PBM population. The responses after antigen infusion
      varied within a wide range both for patients with and without myocardial
      infarction.

PMID- 1980823
TI  - Biology of sarcomas.

PMID- 1980824
TI  - Glycosphingolipid function in cancer.

PMID- 1980825
TI  - Recent advances in hepatitis B viruses and hepatocellular carcinoma.
AB  - The data reviewed at this meeting reinforce the notion that HBV may contribute to
      the development of liver cancer through a variety of mechanisms, including
      activation of oncogenes (c-myc and N-myc) by insertional mutagenesis, expression
      of viral proteins (X and pre-S2/S) that function as trans-activators and possibly
      oncoproteins, and introduction of chromosomal defects through enzymatically
      mediated integration into the host genome. Not all of these mechanisms appear to
      be active in every tumor, however. Thus, future work will be aimed at
      characterizing each mechanism in more detail and determining its relative
      importance in the carcinogenic process.

PMID- 1980826
TI  - The effect of neuroleptic and antiparkinsonian medication on the gag reflex.
AB  - A polygraph assessment of medicated psychiatric patients suggests anticholinergic
      effects are the primary cause of a diminished gag reflex. Sex differences
      indicate that females are relatively protected.

PMID- 1980827
TI  - A comparison of masking effects of haloperidol versus molindone in tardive
      dyskinesia.
AB  - An experimental method was utilized to compare the masking effects of two
      neuroleptic agents--molindone and haloperidol--on 18 neuroleptic-treated
      schizophrenic patients exhibiting operationally defined withdrawal-exacerbated
      tardive dyskinesia. After a week on one of these two medications at
      preestablished doses equivalent to that of the pre-study neuroleptic, molindone
      masked total AIMS scores by significantly less (12%) than haloperidol (27%).
      Similarly, during a second week when the dose of these neuroleptics was
      equivalent to 200% that of the pre-study dose, molindone masked the total AIMS
      score significantly less (23%) as compared to haloperidol (53%). Several
      interpretations of this finding are considered. This study demonstrates the
      feasibility of a method that may offer a model for understanding pharmacological
      differences among neuroleptic medications.

PMID- 1980829
TI  - Hyperventilation: current controversies of definitions and diagnosis. Abstracts
      of papers presented at the Eighth Annual Symposium on Respiratory
      Psychophysiology.

PMID- 1980828
TI  - Combined electroconvulsive and neuroleptic therapy in schizophrenia refractory to
      neuroleptics.
AB  - The results of treatment in 13 schizophrenic patients (nine males, four females)
      who underwent electroconvulsive therapy (ECT) because of varying degrees of
      therapy resistance to neuroleptics (therapy failures, renewed and in some cases
      catatonic exacerbation under neuroleptic therapy, neuroleptic intolerance) are
      reported. The single treatments, which were carried out on average 12 times
      (between six and 20 times), led from very good to good remission in a period of
      between 10 and 7 years in nine patients. Four patients did not respond
      adequately: the small improvement of psychopathology on discharge correlated with
      unfavorable outcome. In three of these patients, the asthenic syndrome was found
      on admission and persisted. In patients with good remission, neuroleptics could
      be reduced after ECT by over 70%, and over 50% in patients with poor remission.
      This result confirms corresponding literature data with regard to neuroleptics.
      The results in this highly selected group also confirm Bleuler's 'one third rule'
      of remissions, also the fact that global outcome does not correlate with response
      to neuroleptics, as well as confirming the relevance of the psychopathological
      state on discharge as an outcome predictor.

PMID- 1980830
TI  - Therapeutic approaches to hyperventilation and asthma. Abstracts of papers
      presented at the Ninth Annual Symposium on Respiratory Psychophysiology.

PMID- 1980831
TI  - Gamma-glutamyltransferase induction by dexamethasone in cytochrome P-450-depleted
      rat liver.
AB  - The effects of the cytochrome P-450 depletion by cobaltic protoporphyrin IX on
      the postnatal glucocorticoid-inducibility of the membrane-bound enzyme gamma
      glutamyltransferase have been assessed in the rat liver. Dexamethasone-induced
      gamma-glutamyltransferase activity in 14-, 28- and 77-day-old rats was high, weak
      and absent, respectively, and inversely correlated with the physiological
      cytochrome P-450 activity. In the liver acinus, the enzyme was reexpressed by the
      zone 1 and zone 2 hepatocytes in suckling rats, substantially only by the zone 1
      hepatocytes in just weaned rats. Following cytochrome P-450 depletion, gamma
      glutamyltransferase induction by dexamethasone was more rapid, more intense and
      more extended in the liver acinus, occurring also in the zone 3 hepatocytes in
      suckling rats, in the zone 2 and a few zone 3 hepatocytes in just weaned rats.
      Further, the enzyme induction occurred also in adult rats in the zone 1 and in
      some zone 2 cells. This shows that cytochrome P-450 modulates the extent of
      hepatic gamma-glutamyltransferase induction by dexamethasone in postnatal rat
      hepatocytes. The phenomenon may be consequent on hormone biotransformation
      changes caused by the cytochrome P-450 depletion.

PMID- 1980832
TI  - Current status of toremifene, a new antiestrogenic agent for the treatment of
      breast cancer. A symposium. San Antonio, TX, USA, December 7, 1989.

PMID- 1980833
TI  - Transmitter release: prepackaging and random mechanism or dynamic and
      deterministic process.
AB  - Stepwise variations in end-plate potential amplitudes that are also multiples of
      spontaneous miniature end-plate potentials (MEPPs) demonstrate a quantal nature
      of evoked transmitter release at the vertebrate neuromuscular junction. Both the
      number of quanta which form relatively small end-plate potentials (EPPs) and the
      time intervals between MEPPs were found to fit Poisson statistics. These
      observations suggested that the release process randomly liberates uniform
      quantities of transmitter. Initial studies showed that quantal size remained
      stable after seemingly high rates of release which was interpreted to indicate
      that a large store of equally sized, equally available, and independently
      releasable quanta are present in the nerve terminals. The observation of numerous
      presynaptic vesicles that contain transmitter provided a morphological basis for
      prepacked transmitter (i.e., quanta). However, physiological studies over the
      last 15 years have yielded data that are difficult to incorporate into the
      quantum-vesicle hypothesis. With normal conditions and during most treatments
      which increase the rate of release, two classes of MEPPs have been found and both
      show a substructure. The bell-MEPP class was characterized by Fatt and Katz and
      the smaller skew-MEPP class has been studied by Kriebel. The ratio of the two
      classes and substructure compositions of both classes are variable. Short series
      of MEPPs and unitary EPPs (U-EPPs) show preferred amplitudes and longer series of
      MEPPs and U-EPPs show stepwise variations in amplitude. Slow-MEPPs and giant
      MEPPs belong to the skew class and represent nearly synchronous bursts of smaller
      MEPPs. Transmitter packet formation, preferred amplitudes, stepwise variations in
      amplitudes, random-like distributions and organized bursts can be simulated by a
      simple deterministic system, the drop formation process, that is known for its
      periodic and chaotic behaviors which are determined by the single parameter of
      flow rate. MEPP intervals, sizes and classes, are also dependent on rates of
      release which demonstrate that the release process(es) is highly organized and
      sensitive to different conditions. We demonstrate that the processes of drop
      formation and release of a packet of transmitter have similar properties and that
      deterministic characteristics describe MEPP and U-EPP time dependencies and
      amplitude substructures. The data and model presented here suggest that packet
      size of acetylcholine may be determined at the moment of release.

PMID- 1980834
TI  - Physiological and behavioral responses to corticotropin-releasing factor
      administration: is CRF a mediator of anxiety or stress responses?

PMID- 1980835
TI  - Actions of 5-HT1 ligands on excitatory synaptic transmission in the hippocampus
      of alert rats.
AB  - 1. The effects of 5-hydroxytryptamine1 (5-HT1) ligands on excitatory synaptic
      transmission were examined in the stratum radiatum of the CA1 region of the
      dorsal hippocampus of alert, gently restrained, rats. 2. 5-HT produced a dose
      dependent reduction in the amplitude of the electrically evoked population
      excitatory postsynaptic potential (e.p.s.p.) when injected directly into the
      hippocampus via a cannula (dose producing 50% maximum inhibition, ED50 = 0.46
      microgram). 3. Direct intrahippocampal (i.h.) application of buspirone (ED50 =
      0.29 microgram), gepirone (1 microgram), ipsapirone (1 microgram), BMY 7378 (0.1
      microgram) and 5-carboxamidotryptamine (5-CT, 0.02 microgram) mimicked the
      inhibitory effect of 5-HT. 4. Systemic injection of buspirone (ED50 = 0.88 mg kg
      1, i.p.), BMY 7378 (0.01 mg kg-1, i.p.) and RU 24969 (1 mg kg-1, s.c.) also had
      an inhibitory effect on the amplitude of the e.p.s.p. 5. Injection of 8-hydroxy-2
      (di-n-propylamino) tetralin (8-OH-DPAT, 2 micrograms) and spiroxatrine (1
      microgram) i.h. alone had no effect on the e.p.s.p. amplitude but prevented the
      inhibitory effect of 5-HT. 6. Systemic injection (i.p.) of methysergide (5 mg kg
      1) and spiroxatrine (1 mg kg-1) antagonized the inhibitory effect of buspirone
      whereas pretreatment with ketanserin (1 mg kg-1), trifluoperazine (1 mg kg-1) and
      idazoxan (1 mg kg-1) had no effect on the response to buspirone. 7. It is
      concluded that hippocampal synaptic transmission is highly sensitive to the
      agonist and antagonist properties of 5-HT1 ligands in the alert rat.

PMID- 1980836
TI  - Contractile and relaxant responses of the canine isolated spinal artery to
      vasoactive substances.
AB  - 1. Effects of vasoactive substances were investigated in the canine isolated
      spinal branch of the intercostal artery (SBICA). 2. Addition of angiotensin II
      (AII), vasopressin, noradrenaline (NA), adrenaline, 5-hydroxytryptamine (5-HT),
      and dopamine each produced concentration-dependent contraction in the SBICA,
      whereas prostaglandin F2 alpha, histamine, and tyramine caused only slight
      contraction. The decreasing order of the potency of contractile agents was AII
      much greater than vasopressin = NA greater than 5-HT greater than adrenaline much
      greater than dopamine. 3. Although the pD2 value for phenylephrine (5.31 +/-
      0.36) was smaller than that for NA (6.48 +/- 0.13), there was no significant
      difference in Emax value between these two agonists in the SBICA. On the other
      hand, xylazine produced only a slight contraction, the pD2 value being 3.59 +/-
      0.08. Phentolamine (10(-8)-10(-6) M) and prazosin (10(-8)-10(-6) M) competitively
      inhibited the NA-induced contraction, while yohimbine (10(-8)-10(-6) M) did not.
      4. Acetylcholine (ACh), sodium nitroprusside (SNP), ATP, ADP, and adenosine
      caused concentration-dependent relaxations in SBICA following contraction with
      NA. On the other hand, isoprenaline up to 10(-4) M did not produce any
      relaxation. The decreasing order of potency of the relaxant agents was ACh
      greater than SNP much greater than ATP = ADP = adenosine. 5. The ACh-induced
      relaxation was competitively inhibited by atropine and was abolished by
      mechanical removal of the endothelium. Aspirin (5 x 10(-5) M) did not affect the
      relaxant response to ACh, while oxyhaemoglobin (10(-5) M) and methylene blue (10(
      5) M) produced significant attenuation. 6. These results suggest that NA produces
      contraction of the isolated canine SBICA which is mainly mediated via alpha 1
      adrenoceptors and that ACh causes a relaxation of the SBICA due to release of
      endothelium-derived relaxing factor (EDRF) from the endothelial cells.

PMID- 1980837
TI  - Anaesthetic suppression of transmitter actions in neocortex.
AB  - 1. The effects of general anaesthetics were investigated on neuronal
      sensitivities to transmitter substances, which were determined by iontophoretic
      applications of acetylcholine, glutamate, N-methyl-D-aspartate (NMDA) and gamma
      aminobutyrate (GABA) during intracellular recording in in vitro slice
      preparations of neocortex (guinea-pig). 2. In most of the 65 neurones studied,
      perfusion of isoflurane (0.5-2.5 minimum alveolar concentration (MAC)) or
      Althesin (25-200 microM) and, in some cases, halothane (0.5-2 MAC), markedly
      reduced the depolarizing responses and associated membrane conductance changes
      evoked by dendritic applications of acetylcholine, glutamate, NMDA and GABA. 3.
      The order of depression was acetylcholine greater than glutamate or NMDA much
      greater than GABA. This selectivity could also be assessed from the EC50 for the
      isoflurane-induced depression of the just-maximal responses to acetylcholine,
      which was 0.9 MAC compared with an EC50 = 1.9 MAC for the suppression of
      glutamate responses. The selectivity was less pronounced in the case of the
      actions of Althesin, where the EC50s were 75 microM for the depression of
      acetylcholine responses and 90 microM for the depression of glutamate responses.
      4. The hyperpolarizing responses observed when GABA was applied near the
      perikaryon in 7 neurones, were slightly reduced (approximately 15%) in 4, and
      unchanged in 3 neurones during anaesthetic application. 5. The pronounced
      depression of the responsiveness to the putative arousal transmitters and an
      observed blockade of acetylcholine-induced potentiation of glutamate actions
      suggest that anaesthetics produce unconsciousness, at least in part, by
      interfering with subsynaptic mechanisms of neocortical activation.

PMID- 1980838
TI  - Increased midbrain dopaminergic cell activity following 2'CH3-MPTP-induced
      dopaminergic cell loss: an in vitro electrophysiological study.
AB  - Several days after the administration of 1-methyl-4-(2'-methylphenyl)-1,2,3,6
      tetrahydropyridine (2'CH3-MPTP) to the BALB/cJ mouse there is a loss of midbrain
      dopaminergic neurons, a reduction of forebrain dopamine (DA) content, and an
      elevation in forebrain DA turnover. The purpose of the present study was to
      determine whether the increase in forebrain DA turnover is related to an increase
      in dopaminergic neuronal activity. In vitro extracellular single unit recordings
      were made from midbrain dopaminergic neurons in the substantia nigra pars
      compacta (nucleus A9) and ventral tegmental area (nucleus A10) of BALB/cJ mice.
      The experimental animals were treated intraperitoneally with 40, 50 or 55 mg/kg
      2'CH3-MPTP and killed 7-15 days later. Forebrain DA concentrations were decreased
      below control values by the two higher toxin doses in the caudate-putamen (67%
      and 78%, respectively), but not in the nucleus accumbens. DA turnover increased
      more than 2-fold in the caudate-putamen, but was unchanged in the nucleus
      accumbens. Nucleus A9 cells, in the 2'CH3-MPTP-treated animals, exhibited a 3
      fold increase in the number of spontaneously active cells, and an 84% increase in
      basal firing rates. There was also a positive correlation between the A9 cell
      firing rates, and the DA turnover in the striatum of the toxin-treated mice.
      Nucleus A10 cells, in the 2'CH3-MPTP-treated animals, exhibited neither changes
      in number of spontaneously active cells nor changes in firing rates.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1980839
TI  - MPTP produces reversible disappearance of tyrosine hydroxylase-containing retinal
      amacrine cells.
AB  - To determine whether 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) alters
      the tyrosine hydroxylase (TH) immunoreactivity of murine dopaminergic retinal
      amacrine cells, 8-10-week-old C57BL/6J mice were treated with i.p. with saline or
      cumulative doses of MPTP ranging from 10 to 300 mg/kg. Paraformaldehyde-fixed
      retinal whole mounts and cross sections were examined using immunochemistry with
      a tyrosine hydroxylase (TH) or a choline acetyltransferase (ChAT) polyclonal
      antibody and an avidin-biotin peroxidase reaction. Both TH+ amacrines and ChAT+
      retinal neurons showed somal and process morphology and distributions that were
      commensurate with previous studies of the same or several related species. At 20
      days following the MPTP treatment, there was a loss of TH+ amacrines according to
      a logarithmic relationship relative to MPTP dosage. The loss ranged from 18 to
      87% for the dosage range without any decrease in the numbers of ChAT+ neurons.
      The TH+ amacrines were deleted randomly from the retinas without any peripheral
      central predilection. By 273 days after MPTP treatment, the number of TH+
      amacrines had returned to values found for age-matched controls demonstrating
      that the loss of TH immunoreactivity was reversible and occurred without
      destruction of TH+ amacrines. Computer densitometry revealed that the MPTP
      treated TH+ amacrines were divided into two distinct populations: one with normal
      TH immunodensity levels and a second with TH immunodensity levels below our
      detection capability. Increasing the MPTP dosage increased the proportion of TH
      amacrines in the second population. The transient and completely reversible
      disappearance in the number of TH+ amacrines: (1) appears to form the basis for
      the decreased concentrations of dopamine and the loss of catecholamine
      fluorescent neurons previously described for MPTP-treated mouse retinae; (2) may
      underlie the defects in the electroretinograms of MPTP-treated monkeys, and (3)
      may result as a response to neurite damage similarly to the alterations in
      protein synthesis in other central neurons following axonal damage.

PMID- 1980840
TI  - A distinctive soma size gradient among catecholaminergic neurones of human
      retinae.
AB  - We have examined the soma diameters and distribution of catecholaminergic (CA)
      cells in human retinae, by using an antibody to tyrosine hydroxylase (TH), the
      rate limiting enzyme in the production of catecholamines. TH-immunoreactivity was
      detected in two classes of cells (CA1 and CA2 cells). CA1 cells had relatively
      large somata (mean diameter 14 microns) located in either the inner nuclear layer
      (INL) or in the ganglion cell layer and extensive dendrites spreading into the
      other strata of the inner plexiform layer (IPL). CA2 cells had smaller, weakly
      labelled somata (mean diameter 9.6 microns) located principally in the inner
      regions of the INL and weakly labelled dendrites extending into the IPL. The mean
      density of CA2 cells in the far retinal periphery was approximately 38/mm2. The
      number of CA1 cells averaged approximately 15,600 per retina, with a mean density
      of 16/mm2. The density distribution of CA1 cells closely paralleled the
      distribution of ganglion cells, their density peaking at the foveal rim, with an
      area of relatively high density extending horizontally from the macula region
      toward the nasal margin (along the visual streak). A distinctive gradient was
      detected among the soma diameters of CA1 cells: they were largest in the mid
      periphery, in a visual streak-like configuration around the optic disk. This
      gradient of soma size among CA cells closely corresponds to the density
      distribution of the rod photoreceptors in human retinae.

PMID- 1980841
TI  - Dose-dependent destruction of the coeruleus-cortical and nigral-striatal
      projections by MPTP.
AB  - In order to determine whether 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
      produces neuronal death or the loss of tyrosine hydroxylase (TH)
      immunoreactivity, 4 catecholaminergic nuclei in the mouse: substantia nigra
      compacta (SNc), locus coeruleus (LC), ventral tegmental area (VTA) and the A13
      nucleus in the hypothalamus were quantitatively examined. Serial sections were
      taken through the rostrocaudal extent of each nucleus: alternate sections were
      incubated with TH antiserum and reacted with an immunoperoxidase technique while
      the alternate set was Nissl stained. Counts and 3 dimensional reconstructions of
      TH reactive somata were made for each nucleus for saline-treated controls and
      mice treated with different doses of MPTP (37.5, 75, 150 and 300 mg/kg). TH
      positive neurons were counted along with their counterparts on the Nissl-stained
      alternative sections to both identify the catecholaminergic neurons and to
      measure their destruction. Concentrations of striatal dopamine and cortical
      norepinephrine were measured for all dosages of MPTP in order to determine the
      relationship between dosage, target tissue neurotransmitter concentration and
      neuronal destruction. By 20 days after MPTP injection there was a dose-dependent
      random loss of TH-immunoreactive neurons that was almost identical in all 4
      nuclei examined. Analysis of the Nissl versus TH cell counts revealed that MPTP
      resulted in neuronal destruction in the SNc and the LC rather than just a loss of
      TH immunoreactivity. There was no difference in sensitivity to MPTP between the
      SNc and the LC. Decreases in cortical norepinephrine concentrations were about
      one third of the decreases of LC neuronal counts for all MPTP doses; while
      decreases in striatal dopamine and SNc cell loss was similar to the LC for the
      two lower doses of MPTP but for the higher doses, the relationship approached or
      exceeded a one to one ratio. Hence estimates of neuronal death based upon target
      tissue transmitter concentrations could not be made using the same relationship
      for SNc and the LC catecholaminergic neurons and use of the same relationship for
      higher MPTP dosages results in an underestimate of LC neuronal destruction
      relative to that in the SNc.

PMID- 1980842
TI  - Arachidonic acid metabolites do not mediate modulation of neurotransmitter
      release by adenosine in rat hippocampus or striatum.
AB  - The possible involvement of arachidonic acid metabolites as mediators of the
      modulation of neurotransmitter release by adenosine, acetylcholine, and GABA was
      examined in brain slices of rat hippocampus and striatum. The synaptic modulatory
      effects of these 3 agents on excitatory transmission in the CA1 region of
      hippocampus were completely unaffected by a phospholipase inhibitor (p
      bromophenacyl bromide, BPB; 10-50 microM), a lipoxygenase inhibitor
      (nordihydroguaiaretic acid; 5-50 microM), the cyclooxygenase inhibitor
      indomethacin (10-20 microM), and a cyclooxygenase/lipoxygenase inhibitor (U53059;
      5-10 microM). BPB was also found to be ineffective in altering the modulation of
      transmission by adenosine in the perforant path, and the adenosine inhibition of
      electrically stimulated release of endogenous dopamine from striatal slices.
      Arachidonic acid itself also had no effect on synaptic transmission. While these
      experiments do not rule out such a role for arachidonic acid or its metabolites
      in mammalian brain, they suggest that in a number of systems the inhibition of
      transmitter release must occur through an entirely independent mechanism.

PMID- 1980843
TI  - Paroxetine as an in vivo indicator of 3,4-methylenedioxymethamphetamine
      neurotoxicity: a presynaptic serotonergic positron emission tomography ligand?
AB  - The present study sought to determine whether [3H]paroxetine, a potent and
      selective inhibitor of serotonin uptake in vitro, could be used to label the
      serotonin transporter in the rat brain in vivo such that it might be employed to
      develop a presynaptic serotonergic positron emission tomography ligand. Tritium
      labeled paroxetine was administered intravenously to rats by means of tail vein
      injection. Four hours later, specific [3H]paroxetine binding was determined by
      subtracting non-specific binding in the cerebellum from total binding in other
      brain regions of interest. The distribution of specific [3H]paroxetine binding
      paralleled the distribution of serotonin uptake sites in all brain regions
      examined. Pretreatment with serotonin re-uptake inhibitors (citalopram or
      sertraline) reduced in vivo specific [3H]paroxetine binding by as much as 99%.
      Specific in vivo [3H]paroxetine binding was further characterized through the use
      of 5,7-dihydroxytryptamine (5,7-DHT), a known serotonergic neurotoxin. 5,7-DHT
      (200 micrograms, i.c.v.) caused a marked reduction in specific [3H]paroxetine
      binding, and induced a prolonged depletion of regional brain serotonin. In a
      final study, the feasibility of using in vivo [3H]paroxetine binding as an
      indicator of serotonergic damage induced by another neurotoxin (3,4
      methylenedioxymethamphetamine, MDMA) was tested. MDMA-treated rats showed a
      profound reduction in in vivo [3H]paroxetine binding, along with a lasting
      depletion of regional brain serotonin. These results demonstrate that
      [3H]paroxetine can be used to label serotonin uptake sites in the rat brain in
      vivo, and that the damage induced by serotonergic neurotoxins can be detected
      using in vivo [3H]paroxetine binding as an indicator. Paroxetine (or one of its
      derivatives) therefore holds promise as a PET ligand for studying serotonergic
      neurons in the living human brain in health as well as after neurotoxic injury.

PMID- 1980844
TI  - Loss of dopamine receptors in the olfactory bulb of patients with Alzheimer's
      disease.
AB  - The presence and localization of dopamine D2 receptors was studied by means of in
      vitro autoradiography with [3H]N-n-propylnorapomorphine in olfactory bulbs
      obtained postmortem from Alzheimer patients and age-matched controls. It appeared
      that, in 5 age-matched controls, the greatest density of dopamine D2 receptors
      was found in the glomerular layer of the bulb. In 6 of 7 Alzheimer patients, the
      labeling of the glomerular layer was decreased so that glomerular and granular
      layer did not differ in labeling density. Tangles, as revealed by Thioflavin S
      staining, were present in all different layers of the bulbus in Alzheimer
      patients. Observation of Nissl-stained preparations revealed that mitral cell
      bodies in bulbs of these patients were not present. Since mitral cells are
      projection neurons with targets in the entorhinal and piriform cortex, the
      observation of loss of these cells supports the hypothesis of early involvement
      of the olfactory system in Alzheimer's disease and the spread from the olfactory
      mucosa and bulb to the cerebral cortex and hippocampus via degeneration of
      interconnecting neurons. Moreover, in vivo detection of bulbar dopamine receptors
      might in the future provide a diagnostic tool for the early detection of senile
      dementia of the Alzheimer type.

PMID- 1980845
TI  - Heterogeneous distribution of cytochrome oxidase activity in the rat substantia
      nigra: correlation with tyrosine hydroxylase and dynorphin immunoreactivities.
AB  - Cytochrome oxidase (COase) activity, an endogenous marker of neuronal activity,
      was examined in the substantia nigra of the adult rat at the light-microscopic
      level. In addition, the pattern of histochemical staining observed for COase
      activity was correlated with immunohistochemistry for tyrosine hydroxylase (a
      marker of dopaminergic neurons) and for dynorphin (a peptide present in afferents
      from the striatum). Differential oxidative metabolic activity was revealed in
      subregions of the substantia nigra by COase histochemistry. Neurons of the
      substantia nigra pars compacta (SNc), ventral tegmental area, and ventrally
      displaced dopaminergic neurons were characterized by little or no staining for
      COase. In contrast, the substantia nigra pars reticulata (SNr) possessed a
      heterogeneous distribution of COase activity that was characterized by denser
      staining in the ventrolateral than the dorsomedial part of the nucleus throughout
      its rostrocaudal extent, with the exception of the most rostral levels. This
      pattern of COase activity was inversely correlated with the density of ventrally
      descending tyrosine hydroxylase-positive dendrites arising from the medial
      portion of the SNc, as well as with the density of dynorphin immunoreactivity.
      The results suggest that the SNc and SNr possess distinct levels of oxidative
      metabolic activity. Furthermore, within the SNr itself, different levels of COase
      activity characterize subpopulations of neurons which may be differentially
      regulated by both striatal and dopaminergic influences.

PMID- 1980846
TI  - Locally evoked potentials in slices of the rat nucleus accumbens: NMDA and non
      NMDA receptor mediated components and modulation by GABA.
AB  - In a slice preparation of the rat nucleus accumbens (Acb), local electrical
      stimulation elicited a field potential composed of two negative peaks, followed
      by a positive wave. The early negative peak was identified as a non-synaptic
      compound action potential, the late negative peak as a monosynaptic population
      spike (PS) and the positive wave as a mixture of an excitatory and an inhibitory
      postsynaptic potential (PSP). Both the PS and the PSP exhibited a marked degree
      of paired-pulse facilitation. The quisqualate/kainate receptor antagonist 6-cyano
      7-nitroquinoxaline-2,3-dione (CNQX; 2 microM) and the broadly acting glutamate
      receptor antagonist kynurenic acid (300 microM) reversibly abolished or reduced
      both the PS and PSP. In contrast, nicotinic, muscarinic and N-methyl-D-aspartate
      (NMDA) receptor antagonists had no suppressive action. Washout of Mg2+ from the
      superfusion medium reversibly enhanced and prolonged the PSP and this effect was
      blocked by the NMDA receptor antagonist D(-)-2-amino-5-phosphonopentanoic acid (D
      AP-5). The gamma-aminobutyric acid antagonist picrotoxin (60 microM) enhanced the
      PS and induced secondary spikes which were superimposed on a prolonged PSP. Most
      of this prolongation was abolished by D-AP-5. It is concluded that locally evoked
      synaptic responses in the Acb are mediated by glutamate or aspartate, and that
      NMDA receptor mediated activity evoked by low frequency stimulation is
      substantial in Mg2(+)-free medium or during reduced GABAA receptor activity, but
      not under normal conditions.

PMID- 1980847
TI  - Neurotoxic effects of excitatory amino acids in the mouse spinal cord:
      quisqualate and kainate but not N-methyl-D-aspartate induce permanent neural
      damage.
AB  - Despite extensive evidence for the neurotoxic effects of excitatory amino acids
      (EAA) in the brain little is known about their neurotoxic action in the spinal
      cord. In this study we attempted to produce differential lesions of spinal
      neurons by pretreating mice, intrathecally, with high concentrations of the EAA:
      N-methyl-D-aspartate (NMDA), quisqualate and kainate. Pharmacological, behavioral
      and histological consequences were examined 1, 3, 7 and, in some cases, 30 days
      after pretreatment. A single, intrathecal, injection of high concentrations of
      quisqualate and kainate but not NMDA, resulted in damage to spinal cord neurons.
      The highest concentrations of these agonists produced, in some animals, a
      massive, non-selective destruction of neurons within the lumbar spinal cord,
      accompanied by complete paralysis of the hindlimbs. Pretreatment with lower
      concentrations of intrathecal kainate or quisqualate produced damage to spinal
      interneurons, as well as more limited damage to motor neurons. No detectable
      motor deficit could be detected but a decrease in responsiveness to noxious
      stimuli was observed. Such damage also manifest as a permanent decrease in the
      sensitivity of the spinal interneurons, as well as more limited damage to motor
      neurons. No detectable motor deficit could be detected but a decrease in
      responsiveness to noxious stimuli was observed. Such damage also manifest as a
      permanent decrease in the sensitivity of the spinal cord to EAA, as seen from the
      decrease in biting behavior elicited by intrathecal EAA. The neurotoxic effects
      of quisqualate were completely blocked by the quisqualate/kainate receptor
      antagonist glutamylaminomethylsulphonate (GAMS), but not the NMDA antagonist 2
      amino-5-phosphovalerate. GAMS attenuated the effects of kainate only
      partially.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1980849
TI  - Electrophysiological evidence for activation of NMDA receptors and its antagonism
      by MK-801 in cerebral ischemia.
AB  - We studied the effects of iontophoretically administered MK-801 (50-150 nA) on
      ischemic changes on the CA1 hippocampal field potential. Twenty rats under
      urethane anesthesia, of which the hippocampal field response was depressed or
      lost upon ligation of the carotid arteries, were used. MK-801 applications
      starting before carotid ligation, decreased the depression of the field response
      in 8 of 11 trials. MK-801 was applied after the appearance of ischemic changes
      and partly restored the deteriorated hippocampal field potential in 16 of 34
      penetrations. MK-801 was ineffective in preventing or restoring the severely
      depressed or lost evoked activity. During ischemia a DC potential shift of -32.6
      +/- 3.7 mV (n = 10) was recorded. MK-801 reduced the amplitude of the DC
      potential shift by 50% when applied before (n = 6) or after (n = 4) the
      initiation of ischemia. Activation of N-methyl-D-aspartate (NMDA) receptors by
      glutamate or N-methyl-DL-aspartate (NMDLA) induces a slow negative wave on the
      field response. During ischemia a similar negative wave spontaneously appeared in
      9 trials and was also induced with low currents (5-10 nA) of NMDLA which were
      insufficient to evoke the NMDA-mediated wave before ischemia. These data provide
      electrophysiological evidence that NMDA receptors are activated during ischemia
      and MK-801 reduces ischemia neuronal dysfunction.

PMID- 1980848
TI  - Methylenedioxymethamphetamine-induced hyperthermia and neurotoxicity are
      independently mediated by 5-HT2 receptors.
AB  - Methylenedioxymethamphetamine (MDMA) produced a significant hyperthermia in rats
      which was antagonized in a competitive manner by the selective 5-HT2 antagonist,
      MDL 11,939. The 5-HT antagonist also blocked MDMA-induced neurotoxicity as
      assessed by the decline in regional 5-HT concentrations observed 1 week later.
      These two effects of MDL 11,939 were dissociated at higher doses of MDMA where
      the antagonist still provided virtually complete protection against the
      neurochemical deficits but only partially attenuated the hyperthermic response.
      In contrast to the effect of the 5-HT2 antagonist, haloperidol did not alter MDMA
      induced hyperthermia but did antagonize its long-term neurochemical effects.
      Similarly, coadministration of the selective 5-HT uptake inhibitor, MDL 27,777,
      did not affect the hyperthermia produced by a high dose of MDMA but completely
      prevented the depletion of 5-HT. When the MDMA-induced hyperthermia was prevented
      by temporarily maintaining animals at reduced ambient temperature, the
      neurochemical changes normally observed 1 week later were also blocked. Although
      these results demonstrate that the drugs tested do not antagonize MDMA-induced
      neurotoxicity by interfering with its effect on body temperature, they do
      indicate that MDMA-induced hyperthermia may contribute to the development of the
      drug's long-term neurochemical effects.

PMID- 1980850
TI  - Expression of somatostatin receptors is impaired in the cerebellum of developing
      Brattleboro rats.
AB  - Somatostatin (SRIF) receptors are expressed in the external granule cell layer of
      the rat cerebellum during early postnatal life. The aim of the present study was
      to investigate the distribution and biochemical characteristics of SRIF binding
      sites in the cerebellum of homozygous (vasopressin deficient) Brattleboro rats,
      which exhibit a selective impairment of their granule cell layer. This study has
      been conducted in 13-day-old rats by means of membrane-binding assay and
      autoradiography using [125I-Tyr0,DTrp8]S14 as a radioligand. In the cerebellum of
      homozygous Brattleboro rats, Scatchard plot analysis revealed the existence of a
      single class of SRIF receptors with similar Kd values as in Long-Evans or
      heterozygous Brattleboro rats (180-200 pM). Conversely, a marked reduction of the
      concentration of SRIF binding sites was observed in Brattleboro rats as compared
      to heterozygous or Long-Evans rats. In homozygous Brattleboro rats,
      autoradiographic studies revealed that the concentration of SRIF receptors was
      reduced in all lobules of the cerebellum as compared to Long-Evans. In addition,
      the magnitude of the decrease of receptor concentration was greater than the loss
      of granule cells observed in the homozygous Brattleboro rat. These results
      indicate that the expression of SRIF receptors by immature granule cells of the
      cerebellum is markedly reduced in Brattleboro rats. Whether the impairment of
      SRIF receptors in diabetes insipidus rats can directly be ascribed to vasopressin
      deficiency remains to be determined.

PMID- 1980851
TI  - DA2/NT receptor balance in the mesostriatal and mesolimbocortical systems after
      chronic treatment with typical and atypical neuroleptic drugs.
AB  - Typical and atypical neuroleptic drugs show several clinical and behavioral
      effects, possibly related to the different anatomical sites of the action in the
      mesolimbocortical or mesostriatal dopaminergic systems. Because of the
      interaction between dopamine (DA) and neurotensin (NT) in the target areas of
      these systems, and in order to study if the different action of typical and
      atypical neuroleptic drugs could be related to a modification of the DA/NT
      balance, we investigated DA2 and NT receptor modifications--by means of
      quantitative receptor autoradiography--after chronic treatment with low dosage of
      haloperidol, chlorpromazine, thioridazine and clozapine. We described a decrease
      of NT receptor density in the target areas of the mesolimbocortical system
      produced by all the treatments. This effect does not match with DA2 receptor
      modifications. On the contrary, the block of DA transmission obtained by high
      dosage of haloperidol induces an increase of NT receptor density. Our results
      further demonstrate the regulation of NT transmission by DAergic drugs.

PMID- 1980852
TI  - Long-term survival of GABA-, enkephalin-, NADPH-diaphorase- and calbindin-d28k
      containing neurons in fetal striatal grafts.
AB  - Neurons in long-term striatal grafts were examined to determine if they retain
      the neurotransmitter characteristics of cells in younger grafts. In addition,
      calbindin-d28k, a ubiquitous marker of medium spiny neurons, was used to examine
      the overall frequency and ultrastructural characteristics of spiny neurons in the
      older grafts. Grafts from 17-day fetal striata were injected into the quinolinic
      acid-lesioned caudate nucleus in 5 adult rats. After 16 months, the neostriatum
      was processed for the localization of immunoreactive GABA, calbindin, enkephalin
      and NADPH-diaphorase (-d) activity. The proportions of GABA-, enkephalin- and
      NADPH-d-labeled neurons to total Nissl-stained neurons in the 16-month-old grafts
      (25 +/- 6, 13 +/- 4, and 3 +/- 3, respectively) were similar to findings in 2
      month-old grafts. Calbindin-positive cells formed the highest proportion (36.3 +/
      3) of labeled neurons in the older grafts. Nuclear and spine morphology of
      immunoreactive calbindin cells varied more in the grafts than in host caudate.
      Results show that there is long-term survival and stability of GABA, enkephalin
      and NADPH-d cell populations in the grafts and that some grafted spiny neurons
      may exhibit altered phenotype from those of host striatum.

PMID- 1980853
TI  - Dynorphin A: in vivo release in the spinal cord of the cat.
AB  - The antibody microprobe technique was used to study the release of immunoreactive
      dynorphin A within the lower lumbar spinal cord of anaesthetised cats. A basal
      release was observed in the dorsal horn, centered in the region of lamina I, but
      was abolished by spinal cord transection at the thoracolumbar junction. Release
      of dynorphin A in the lamina I region was evoked by high-frequency electrical
      stimulation of unmyelinated primary afferent fibres, whereas stimulation of
      myelinated (including A delta) afferents was ineffective. Evidence was also
      obtained for release in laminae V-VI and at the spinal cord surface. These
      results suggest that in the lumbar spinal cord of the cat, dynorphin A is
      released in the superficial dorsal horn by impulses in descending pathways and in
      somatic unmyelinated primary afferent fibres.

PMID- 1980854
TI  - Anti-IgE- and anti-IgA-induced eosinophil migration in atopics and healthy
      volunteers.

PMID- 1980855
TI  - Immunology and treatment of mosquito bites.
AB  - Cutaneous reactions to mosquito bites are usually pruritic weals and delayed
      papules. Arthus-type local and systemic symptoms can also occur but anaphylactic
      reactions are very rare. Both clinical and experimental evidence suggest that the
      various bite reactions result from sensitization to the mosquito saliva injected
      into the skin during feeding. Recent immunoblot studies have shown both IgG- and
      IgE-class anti-mosquito antibodies, but their species-specificity and clinical
      importance is at present unknown. In addition to an Arthus-type mechanism, both
      cutaneous late-phase reactivity and cell-mediated immunity may be involved in the
      pathophysiology of delayed mosquito-bite lesions. Cutaneous sensitization to
      mosquito bites can be divided into five different stages ranging from the stages
      of immediate wealing and delayed bite papules, to the stage of non-reactivity. No
      desensitization treatment is generally available for mosquito allergy but it has
      recently been shown that cetirizine, a potent non-sedating antihistamine, is
      effective against the wealing and pruritus caused by mosquito bites.

PMID- 1980856
TI  - Histamine, antihistamines and atopic eczema.
AB  - Histamine is known to be a classical inducer of pruritus. In atopic eczema, itch
      is a prominent feature (regarded by some even as a 'primary lesion'!). One of the
      most potent chemical mediators of itch is histamine. Histamine, together with
      other mediators may play a role in the pathophysiology of atopic eczema: the
      increased release of histamine from basophil leucocytes of atopic patients has
      been described, as well as elevated histamine levels in plasma and skin during
      acute exacerbations of eczematous lesions. Therefore, application of H1
      antagonists seems to be a rational regime in the symptomatic treatment of atopic
      eczema. Nevertheless, some controversy exists regarding the clinical efficacy of
      orally applied H1 antagonists in this disease, especially with regard to the
      newer non-sedating compounds such as terfenadine, astemizole, loratadine and
      cetirizine. Review of the literature shows that there are studies demonstrating a
      clear-cut antipruritic effect of non-sedating H1 antagonists. Thus the sedative
      action does not seem necessarily to be connected with therapeutic efficacy in
      treating itch in atopic eczema. Newer studies show that cetirizine exerts an
      additional inhibitory effect on eosinophils. This may broaden the therapeutic
      spectrum of this H1 antagonist in diseases with eosinophil involvement.

PMID- 1980857
TI  - Late-phase cutaneous reactions to platelet activating factor and kallikrein in
      urticaria.

PMID- 1980858
TI  - [Early repair of deep burns of the foot].
AB  - Early repair of 11 feet of 10 burned patients over four-year period was
      presented. The injured or necrosed vessel, tendon, nerve and bone joint were
      retained during debridement and covered with different kind of flaps including
      free flap. The good appearances and functions were obtained in 9 feet, one ankle
      joint showed slightly disability and five digits of the rest feet were amputated.
      The characteristics of the burned foot was also discussed in this paper.

PMID- 1980859
TI  - [Use of free flaps for covering deep burns in functional sites].
AB  - From July 1980 to July 1988, 10 free flaps were used to cover deep burn on wrist,
      elbow, heel and hand. The wounds can be closed in time and the functions can be
      rehabilitated early. The results were not satisfied if the traditional methods
      were used to cover the infected and necrotic muscle, tendon, nerve, blood vessel,
      bone and joint due to electric, hot compressed or flame burns. The choice of
      using free flaps should be very careful because the operation time is relatively
      longer, the procedure is more complex, and the general condition of the patient
      may be interfered. The more serious results may be got if the free flap does not
      survive. It is recommended to use antero-lateral femoral free flap, because the
      sites of blood vessels are constant, the donor area can be hidden from view, the
      thickness and softness are satisfied.

PMID- 1980860
TI  - A guide to benzodiazepine selection. Part I: Pharmacological aspects.
AB  - Since absorption rates, volumes of distribution and elimination rates differ
      greatly among the benzodiazepine derivatives, each benzodiazepine has a unique
      plasma concentration curve. Although the time to peak plasma levels provides a
      rough guide, it is not equivalent to the time to clinical onset of effect. Two
      half-lives can be described: the alpha half-life, the rate of decline in plasma
      concentrations due to the process of drug redistribution from the central to the
      peripheral compartment, and the beta half-life, the rate of decline due to the
      process of drug elimination due to metabolism. The frequent classification of
      benzodiazepines into long, intermediate, and short-"acting" categories based on
      their terminal beta half-lives is unfounded; the duration of action is much more
      dependent on the alpha half-life. Benzodiazepines with short beta half-lives are
      commonly thought to be preferable because they accumulate less. However, with
      repeated use, sedation and cognitive neuromotor impairment usually diminish
      progressively despite stable or even rising benzodiazepine plasma concentrations,
      whereas anxiolytic effects generally persist over time.

PMID- 1980861
TI  - Depressive stupor and chlordesmethyldiazepam.

PMID- 1980862
TI  - Amniotic fluid microvillar enzyme activity in fetal malformations.
AB  - Prenatal diagnosis of cystic fibrosis based on amniotic fluid microvillar enzyme
      activity assay has become routine practice in the past few years. Normal (median)
      values of these enzymes were determined in 177 normal healthy pregnancies between
      15-20 gestational weeks and were related to enzyme values measured in 50
      pregnancies complicated with congenital malformations, 6 monogenic inherited
      diseases and 4 chromosomal aberrations. It is concluded that increased trehalase
      activity has diagnostic importance in detecting fetal kidney diseases, and radial
      renal syndrome (with elevated GGT activity), while low enzyme activities may
      indicate chromosomal aberrations (with no signs of intestinal obstruction). With
      the collection of further data, the analysis of these enzymes might provide an
      opportunity to set up diagnostic procedures for the detection of other, non-CF
      related cases.

PMID- 1980864
TI  - First International Conference on Advances in Clinical Haematology: Current
      practice and future directions for quality assessment in laboratory haematology.
      Durham, North Carolina, 18-19 September 1989.

PMID- 1980863
TI  - Dopaminergic treatments for hyperprolactinaemia.
AB  - Hyperprolactinaemia is a frequent cause of anovulatory sterility, although
      spontaneous pregnancy may occur occasionally. Dopaminergic treatment is highly
      effective for the treatment of both idiopathic and tumoral hyperprolactinaemia.
      If the only cause of infertility is chronic anovulation due to
      hyperprolactinaemia, an 80% pregnancy rate can be anticipated. Because of these
      results, surgical treatment is still needed only rarely. Pregnancy, either
      spontaneous or drug-related, is usually uneventful for the mother and is not
      associated with any increase in abortion, twins or malformations. Pregnancy
      related tumour growth occurs rarely and can be treated successfully with
      dopaminergic drugs. On the contrary, there is more frequently improvement after
      pregnancy of the biochemical and clinical disorders associated with
      hyperprolactinaemia.

PMID- 1980865
TI  - Cytokines and infections (AIDS excluded): Eleventh Symposium of the Pharmaco
      clinique Roussel-Uclaf, Paris, 8-9 June 1989.

PMID- 1980866
TI  - Comparison of hepatic drug metabolizing enzymes in three-month-old lambs and
      kids.
AB  - 1. The comparative activity of hepatic cytochrome P-450 monooxygenase system,
      glucuronyl-transferase, glutathione S-transferase and N-acetyltransferase was
      studied in three-month-old male and female Lacaune lambs and male Saanen kids. 2.
      The study of mixed-function oxidase components showed that total cytochrome P-450
      ranged from 0.54 in kids to 0.85-0.88 nmol/mg-1 in lambs. Male lambs had higher
      levels than kids (122-165%) for aminopyrine, benzphetamine, ethylmorphine and
      erythromycin demethylases or benzo(a)pyrene hydroxylase whereas NADPH-cytochrome
      c reductase was 1.19-fold lower in lambs. 3. Sex-related changes were observed in
      lambs in case of microsomal benzo(a)pyrene hydroxylase activity which appeared
      1.31-fold more potent in male liver. Cytosolic N-acetyltransferase accepting
      sulfamethazine as substrate was about 8-fold higher in female than in male lambs.
      4. The analysis of samples from various liver lobes, indicated the heterogenous
      distribution of microsomal proteins which is related to higher concentrations of
      both cytochrome b5, NADPH-cytochrome c reductase and p-nitrophenol
      glucuronyltransferase in left lobes.

PMID- 1980867
TI  - The frog spinal cord: a model to study methanethiol-central nervous system
      interaction.
AB  - 1. The effects of methanethiol (MT), DL-dithiothreitol (DTT) and N-ethyl
      maleimide (NEM) were studied on the electrical activities of the frog cord. 2.
      Methanethiol depressed spontaneous dorsal and ventral root potentials, whereas no
      effects were observed on evoked responses. 3. N-ethyl-maleimide, a SH modifying
      agent, irreversibly depressed electrical cord activities. 4. DL-Dithiothreitol, a
      SH reducing agent, dramatically increased spontaneous electrical cord pattern. 5.
      It is suggested that interneuronal membrane sulphydryl groups of dorsal horn cell
      population are involved in the origin of spontaneous electrical cord activities
      and that MT interacts with these interneurones, probably oxidizing membrane SH
      groups.

PMID- 1980868
TI  - Muscarinic receptor activity change after prolonged treatment with growth hormone
      and somatostatin.
AB  - 1. The effect of 10-day treatment with growth hormone (GH) (1 mg/kg body weight
      day) and somatostatin (SRIF) (0.25 mg/kg body weight day) subcutaneously on the
      activity of muscarinic (M) receptors in rat hypothalamic, pituitary and cerebral
      cortical membrane fractions was studied using (3H)quinuclidinyl benzylate
      [(3H)QNB] as radioligand. 2. The administration of GH and SRIF significantly
      decreased the M-receptor binding affinity in the hypothalamus. 3. In the
      pituitary the M-receptor affinity was increased after both GH and SRIF treatment.
      4. In the hypothalamus and the pituitary the binding capacity of muscarinic
      receptors was unchanged. 5. In the cerebral cortex the chronical GH injection
      induced an increase in the number of antagonist binding sites and a decrease of
      their affinity, while the similar SRIF treatment led to an increase of the
      binding affinity without any change of M-receptor capacity. 6. These results
      indicate that GH and SRIF selectively and region-specifically modulate muscarinic
      receptor binding affinity and capacity and provide new insight into the feedback
      regulatory mechanisms of GH secretion.

PMID- 1980869
TI  - Morphine induces aggression but not analgesia in the naked mole-rat
      (Heterocephalus glaber).
AB  - 1. The antinociceptive effect in the mole-rat of morphine (1, 10, 20 or 30 mg/kg)
      and nefopam (10 or 20 mg/kg) was studied. 2. In the hotplate test, morphine had
      no analgesic effect. A reduced response latency after morphine (10 and 20 mg/kg)
      could possibly be explained by hyperactivity and excited behaviour. 3. After
      morphine (10, 20 and 30 mg/kg) most of the animals died after fighting when kept
      in colony cages. Aggressive behaviour and death was prevented by naloxone, or by
      keeping the animals in single cages. 4. Nefopam (20 mg/kg) significantly
      increased the latency for the nociceptive response. 5. It was concluded that in
      the mole-rat, opioid systems in the CNS may not be involved in the regulation of
      nociception, but in the regulation of agonistic and motor behaviour.

PMID- 1980871
TI  - Autonomic control of heart rate in the adult, aquatic Notophthalmus viridescens
      viridescens.
AB  - 1. We investigated the role of the autonomic nervous system in the control of the
      heart rate using an isolated heart preparation. 2. Addition of the
      parasympathetic blocker, atropine, to the organ bath resulted in an increase in
      heart rate as expected. 3. Addition of the sympathetic blocker, ergotamine, to
      the organ bath showed no change in the heart rate. 4. Addition of the sympathetic
      blocker, propranolol, to the organ bath resulted in the expected decrease in
      heart rate. 5. Both the sympathetic and parasympathetic nervous systems appear to
      play a role in the control of the heart rate.

PMID- 1980870
TI  - Transmitter release modulated by isoprenaline in the dog isolated mesenteric
      vein.
AB  - 1. The effects of isoprenaline on the release of transmitter substances from
      perivascular adrenergic nerves were estimated from the excitatory junction
      potential (ejp) and outflow of noradrenaline in the dog mesenteric vein. 2.
      Isoprenaline increased the ejp amplitude and decreased the evoked release of
      noradrenaline. Yohimbine potentiated the former and converted the latter to an
      increased outflow. 3. Therefore, stimulation of prejunctional beta-adrenoceptor
      by isoprenaline increases the release of noradrenaline from perivascular
      adrenergic nerves. 4. Possible involvement of prejunctional alpha-adrenoceptors
      in the isoprenaline-induced modulation of transmitter release was also suggested.

PMID- 1980873
TI  - Purification and characterization of cytochrome P-450 isozymes from phenobarbital
      induced adult hen liver.
AB  - 1. Two cytochrome P-450 isozymes (P-450 PB-A, PB-B) and cytochrome b5 were
      purified from livers of phenobarbital-treated adult hens. 2. Both the enzymes
      exhibited the same apparent molecular weight (54,000). 3. They could be
      distinguished on the basis of immunochemical properties, spectral properties,
      peptide pattern after partial proteolysis, tryptic peptide pattern, and N
      terminal sequence. 4. The antibodies raised against P-450 PB-A and PB-B did not
      cross-react with microsomal P-450s of rat, mice, cat, or catfish species by
      immunoblotting.

PMID- 1980872
TI  - Threonine6-bradykinin in the venom of the wasp Colpa interrupta (F.)
      presynaptically blocks nicotinic synaptic transmission in the insect CNS.
AB  - 1. The venom of the solitary scoliid wasp Colpa interrupta (F.) shows a kinin
      activity, when tested on a cascade of mammalian smooth muscle preparations, and,
      in addition, a contraction of the rat colon. 2. The venom also irreversibly
      blocks the nicotinic synaptic transmission from the cercal nerve to a giant
      interneuron in the sixth abdominal ganglion of the cockroach, Periplaneta
      americana. 3. The same activities have been found within one HPLC fraction. 4.
      However, rechromatography of this fraction resulted in four subfractions being
      active on smooth muscles. 5. One fraction caused contraction of the colon, three
      other fractions contained kinin-activity. 6. Only the most active kinin fraction
      blocked synaptic transmission in the insect CNS. 7. This fraction contained
      threonine-bradykinin. 8. Synthetic Thr-bradykinin causes irreversible presynaptic
      activation-induced block of transmission in the insect CNS.

PMID- 1980874
TI  - Accumulation and metabolism of 2,4,6-trichlorophenyl-4'-aminophenyl ether by
      carp.
AB  - 1. Accumulation of 2,4,6-trichlorophenyl-4'-aminophenyl ether (CNP-amino) in carp
      was investigated for 14 days. CNP-amino in carp could be divided into free CNP
      amino [CNP-amino(I)] and bound CNP-amino [CNP-amino(II)]. 2. The bioconcentration
      factors (BCF) of CNP-amino(I + II) in carp were 90 +/- 38 (mean +/- SD, n = 3)
      for muscle, 402 for liver, 501 for kidney and 5368 for gallbladder after 14 days
      exposure. 3. 2,4,6-Trichlorophenyl-4'-acetamide phenyl ether (CNP-acetamide) was
      detected as metabolites of CNP-amino in muscle and viscera of carp.

PMID- 1980875
TI  - Cyanide intoxication. II. The effects of systematic cyanide challenge on
      indicative toxicity parameters.
AB  - 1. Present studies were carried out to establish the action of cyanide maintained
      at a high level during a period as long as desired. 2. One of the earliest
      effects of cyanide seems to be the inhibition of hepatic rhodanese. These changes
      do not seem to occur in the blood. 3. Available cyanide labile-sulfur was always
      altered, unless cyanide tissue levels could not be detected. 4. The inhibitory
      action of cyanide on enzymatic reaction involving Schiff base intermediates was
      also corroborated through its effect on delta-aminolevulinate acid dehydratase
      activity. 5. S-Adenosyl-L-methionine was not able to modify the toxic cyanide
      action.

PMID- 1980876
TI  - The effects of pentachlorophenol (PCP) at the toad neuromuscular junction.
AB  - 1. Effects of PCP at the frog neuromuscular junction were studied in vitro in
      sciatic nerve sartorius muscle of the toad Pleurodema-thaul. 2. Within the
      concentration 0.003-0.1 mM, PCP caused a dose-time-dependent block of evoked
      transmitter release acompanied by an increase in the rate of spontaneous quantal
      release. 3. PCP induced an increase in miniature endplate potential (MEPP)
      frequency and it was not antagonized in a Ca2(+)-free medium, indicating that it
      does not depend upon Ca2+ influx from the external medium, but may act by
      releasing Ca2+ from intraterminal stores. 4. The present data, together with
      previous results concerning PCP at eighth sympathetic ganglia indicate that 3,4
      diaminopyridine (3,4-DAP) counteracts the effects of PCP on synaptic
      transmission. This result suggests that PCP interfering Ca2+ influx occurs during
      depolarization of motor nerve terminals.

PMID- 1980877
TI  - A slow and a fast secretory compartment of POMC-derived peptides in the
      neurointermediate lobe of the amphibian Xenopus laevis.
AB  - 1. Peptide release from the neurointermediate lobe of Xenopus laevis has been
      studied using dual pulse-chase incubation, superfusion and HPLC techniques. 2.
      Lobes release pulse-labelled material in two phases, the first phase lasting
      about 6 hr, the second persisting up to 14 hr. 3. In both phases similar, POMC
      derived peptides are released. Their release can be inhibited by dopamine. 4.
      When release during the first phase is inhibited, newly synthesized peptides are
      shunted into the second release pathway. 5. It is concluded that the
      neurointermediate lobe contains two release compartments. The possible locations
      of these compartments within melanotrope cells have been discussed.

PMID- 1980878
TI  - Central versus peripheral opioid regulation of ingestive behavior in the domestic
      fowl.
AB  - 1. Three experiments were conducted to determine whether opioid regulation of
      ingestive behavior in the domestic fowl is mediated at sites within the central
      nervous system (CNS) or peripheral tissues. 2. Food and water intake were
      significantly decreased by the intramuscular (im) injection of naloxone
      hydrochloride (NHCl) and naloxone methobromide, which have a high and low
      ability, respectively, to cross the blood-brain barrier. 3. Water, but not food,
      intake was significantly decreased by the intracerebroventricular (ICV) injection
      of NHCl. However, water intake was not affected by the im injection of doses
      which were effective when given ICV. 4. These results suggest that in the
      domestic fowl there is a peripheral component to opioid regulation of food
      intake, while opioid regulation of water intake seems to be mediated at
      peripheral sites and within the CNS.

PMID- 1980879
TI  - Drug metabolism in Octodon degus: low inductive effect of phenobarbital.
AB  - 1. Differential effects of phenobarbital pre-treatment on liver microsomal drug
      metabolizing enzymes were registered in Octodon degus. 2. Glucuronidation
      reaction for morphine was decreased but that for p-nitrophenol was significantly
      increased. 3. Oxidative reactions such as naphthalene hydroxylation, morphine and
      aminopyrine N-demethylation were modestly increased. 4. In phenobarbital treated
      Octodon degus, testosterone metabolic pathways were decreased, not inducible or
      absent. 5. Spectral studies revealed two binding sites with different affinities
      for aniline in Octodon degus liver microsomes. 6. The poor phenobarbital
      induction on drug metabolism in Octodon degus may be a result of deficiency of
      androgen metabolic pathways associated to drug metabolizing enzymes.

PMID- 1980880
TI  - Bioconcentration and excretion of diazinon, IBP, malathion and fenitrothion by
      carp.
AB  - 1. Bioconcentration and excretion of diazinon, IBP, malathion and fenitrothion
      were studied for carp (Cyprinus carpio L.). 2. The concentrations of these
      pesticides in muscle and viscera of the carp reached plateaus in 12-48 hr
      exposure. 3. The average values of bioconcentration factors (BCF) for diazinon
      were 20.9 in muscle, 60.0 in liver, 111.1 in kidney and 32.2 in gallbladder over
      the 168 hr exposure period. Similarly, those values were 4.3-26.7 for IBP, 2.7
      17.3 for malathion, and 36.0-157.1 for fenitrothion. 4. The excretion rate
      constants of malathion (hr-1) were 0.13 for muscle, 0.12 for liver, 0.08 for
      kidney and 0.06 for gallbladder. Those of diazinon, IBP and fenitrothion (g.ng
      1.hr-1) were 0.002-0.024 for muscle, 0.001-0.020 for liver, 0.0004-0.004 for
      kidney and 0.002-0.023 for gallbladder, respectively.

PMID- 1980881
TI  - Some selected haematological indices in Wistar rats in the vanadium-ethanol
      interaction.
AB  - 1. Wistar rats of both sexes daily received an ethanol solution of ammonium
      metavanadate (AMV) of 0.3 mg V/cm3 5% ethanol concentration as sole drinking
      liquid, for a period of 4 weeks. 2. The reference groups received for drinking
      aqueous AMV solution, or 5% ethanol, or water. 3. In animals drinking both water
      and ethanol AMV solution a decrease in the erythrocyte count and haemoglobin
      level was noted together with an increase of the percentage of reticulocytes and
      polychromatophilic erythrocytes in the peripheral blood. 4. A small rise of the
      percentage of polychromatophilic and orthochromatic erythroblasts was at the same
      time noted in the bone marrow of animals receiving ethanol AMV solution. 5. In
      the group of animals drinking 5% ethanol a fall of the erythrocyte count was
      observed and a rise of the leukocyte count, particularly of lymphocytes. 6.
      Substitution of water by 5% ethanol solution as solvent for AMV did not have any
      distinct influence on the toxicity of the tested compound.

PMID- 1980882
TI  - Inositol-1,4,5-trisphosphate and non-hydrolysable GTP analogue induced calcium
      release from intracellular stores of the Helix pomatia neurons.
AB  - 1. Cytoplasmic Ca2+ concentration ICaIin and membrane potential of single Helix
      pomatia neurons was studied by Fura-2 fluorescence measurement and conventional
      current clamp methods. 2. Intracellular injection of inositol-1,4,5-trisphosphate
      (IP3) and nonhydrolysable GTP analogue (Gpp/NH/p) led to a rise of ICaIin; in
      contrast, GTP injection did not cause significant ICaIin changes. 3. We suggest
      that both IP3 and Gpp/NH/p directly activated Ca release from intracellular
      stores.

PMID- 1980883
TI  - In vitro metabolism of delta-11-tetrahydrocannabinol in the mouse, rat, guinea
      pig, rabbit, hamster, gerbil and cat.
AB  - 1. Liver microsomes were prepared from rats, rabbits, guinea pigs, hamsters,
      gerbils, a cat and three strains of mice, and were incubated with delta-11
      tetrahydrocannabinol (delta-11-THC). The extracted metabolites were separated by
      chromatography on Sephadex LH-20 and examined by gas chromatography and combined
      gas chromatography/mass spectrometry. 2. Eleven metabolites were identified;
      these were formed by aliphatic hydroxylation of all positions of the pentyl
      chain, allylic hydroxylation at C-10 and C-8 (alpha and beta), and by the epoxide
      diol pathway. 3. The ratio of the metabolites varied considerably between the
      species. Mice and rats favoured hydroxylation at C-8-alpha with very little
      hydroxylation of the pentyl chain. 4. In the guinea pig, however, hydroxylation
      of the pentyl chain, particularly at C-4', produced the major metabolites; very
      little hydroxylation occurred at C-8. 5. Side-chain hydroxylation was also
      favoured by the gerbil. 6. In the cat and hamster, 8-beta-hydroxylation was by
      far the major metabolic route, accounting, in the cat, for nearly 70% of the
      recovered metabolites. 7. The rabbit, on the other hand, favoured the epoxide
      diol pathway with over 70% of the recovered metabolites being accounted for by
      the 9,11-dihydro-diols. 8. The results emphasise the need to make appropriate
      choices of animal models for metabolic and toxicological studies in humans.

PMID- 1980884
TI  - Amiloride inhibits contraction and serotonin modulation of Aplysia muscle.
AB  - 1. Serotonin (5-HT) potentiates acetylcholine (ACh)-elicited contractions of
      Aplysia buccal muscles. Serotonin potentiation was significantly reduced by 0.03
      mM, 0.1 mM, and 0.3 mM amiloride. 2. Unpotentiated ACh-elicited contractions were
      significantly reduced by 0.1 mM and 0.3 mM amiloride. 3. Amiloride reduced ACh
      elicited depolarization. The reduction in contraction caused by 0.3 mM amiloride
      (to 16% of control) was larger than could be explained by the reduction in
      depolarization (86% of control). 4. Amiloride had no effect on tension in skinned
      muscle fibers, indicating that amiloride probably did not have a direct effect on
      contractile mechanisms. 5. Potentiation of contraction produced by zero sodium
      (Tris substituted, 0 Na-Tris) medium could be abolished by 0.3 mM amiloride. 6.
      Zero Na-Tris increased 45Ca influx 2.7-fold. In the presence of 0.3 mM amiloride,
      0 Na-Tris increased 45Ca influx only 1.4-fold. 7. Amiloride (0.3 mM) reduced the
      elevation of muscle cAMP caused by 10(-6) M 5-HT by 60%. Zero Na-Tris did not
      cause a change in muscle cAMP.

PMID- 1980885
TI  - Carrageenans solubilize asymmetric acetylcholinesterase from nicotinic
      cholinergic synapses.
AB  - 1. Acetylcholinesterase (AChE) catalyzes the hydrolysis of acetylcholine at
      cholinergic synapses in both vertebrate and invertebrates organisms. 2. The
      asymmetric synaptic AChE is attached to the extracellular matrix (ECM) of the
      neuromuscular junction through heparin sulphate proteoglycans (HSPGs). 3. It has
      been shown previously that heparin-like glycosaminoglycans (GAGs) can solubilize
      this enzyme from the cholinergic synapses. 4. The present paper describes the
      solubilization of asymmetric AChE by different marine macroalgal polysaccharides,
      called carrageenans. 5. Important differences were found among all the
      carrageenans tested; they released 15-50% of the total AChE activity normally
      solubilized by heparin. 6. Carrageenans extracted from tetrasporic stages of
      Iridaea ciliata and I. membranacea were always better extracting agents than
      those from the cystocarpic stages of these algae, suggesting that lambda-like
      carrageenans are involved. 7. This hypothesis was confirmed by extracting AChE
      with purified carrageenans.

PMID- 1980886
TI  - Effect of anti-inflammatory drugs on the activity of antioxidant enzymes and in
      vivo peroxidation products in the liver and kidney of rat.
AB  - 1. Four groups of rats were injected with four different anti-inflammatory drugs
      (indomethacin, phenylbutazone, acetylsalicylic acid and hydrocortisone) and the
      activities of superoxide dismutase, catalase and glutathione peroxidase were
      studied in the liver and kidney. 2. The drugs treatment resulted in decreased
      activity of the enzymes in both organs compared to the control animals. 3. In
      vivo tissue peroxidation was also effected by the drugs used. 4. Our results
      indicate that the changes of oxygen free-radical metabolism contribute to the
      action of these drugs in vivo.

PMID- 1980887
TI  - Monoamine oxidase activity in embryos of pike (Esox lucius).
AB  - 1. Mitochondrial MAO specific activity was measured in eggs and early embryos of
      the teleostean fish Esox lucius using tryptamine, 5-hydroxytryptamine (5-HT) and
      phenylethylamine (PEA) as substrates. 2. Tryptamine is the most readily
      deaminated substrate in mitochondria isolated from unfertilized eggs and embryos
      at the stages of cleavage, blastula and gastrula. 3. Monoamine oxidase activity
      gradually decreases during development and at the gastrula stage it is
      respectively 80% (tryptamine), 70% (5-HT) and 50% (PEA) of that found in the egg
      using the corresponding substrate. 4. The inhibition of egg MAO activity by
      clorgyline and deprenyl measured in E. lucius eggs using tryptamine as substrate,
      indicates the presence of a single form of MAO not corresponding to the MAO A and
      MAO B described in terrestrial vertebrates.

PMID- 1980889
TI  - [Prenatal diagnosis of hemophilia A by DNA analysis].
AB  - Prenatal diagnosis of hemophilia A and B was carried out in our hospital by DNA
      analysis in early and late villi and amniotic cells. Fifteen women with family
      history of hemophilia were studied by different sets of DNA probes and
      restrictive enzymes from Nov. 1986 to March 1989. Two of the 15 women were proved
      not carriers by blood sample assaying. Two did not show sites of polymorphism and
      another was not reported owing too small a DNA sample of amniotic cells. Among
      other 10 cases, 4 were proven normal male fetus, 1 proven affected male fetus was
      induced, and 5 were proven female fetus with 2 carriers.

PMID- 1980888
TI  - Isoelectric analysis of 3H-pargyline-labelled monoamine oxidase in rat and carp.
AB  - 1. After selective binding of [3H]pargyline to either monoamine oxidase (MAO) A
      or MAO B in the rat liver, MAO B alone in the rat brain and MAO in carp brain and
      liver, molecular weight and isoelectric points (pI) of these MAO were determined
      by sodium dodecyl sulphate (SDS)-polyacrylamide gel electrophoresis and
      isoelectric focusing and results obtained were compared. 2. For all tissues
      tested, SDS-polyacrylamide gel electrophoresis of [3H]pargyline-bound samples
      revealed a labelled protein band of an apparent mol. wt of 60,000 da. 3.
      Estimation of radioactivity of [3H]pargyline bound after isoelectric focusing
      revealed a single protein band with acidic pI values of about 5.5 for rat brain
      and liver MAO B. 4. Moreover, the pI values of about 7.5 were obtained for carp
      brain and liver MAO. This basic value was also found for MAO A in the rat liver
      MAO A.

PMID- 1980890
TI  - Alpha 1-adrenoceptor stimulation increases intracellular pH and Ca2+ in
      cardiomyocytes through Na+/H+ and Na+/Ca2+ exchange.
AB  - The effects of alpha 1-adrenergic stimulation on intracellular pH (pHi) and Ca2+
      concentration ([Ca2+]i) were investigated in isolated rat cardiomyocytes with
      fluorescence dyes, BCECF and fura-2, respectively. In the presence of 5 or 25 mM
      HCO3- norepinephrine (NE) increased pHi in a dose-dependent manner. Intracellular
      alkalinization was inhibited by prazosin and phentolamine but not by yohimbine.
      NE-induced alkalinization was inhibited in the presence of a Na+/H+ exchange
      inhibitor (5-(N,N-hexamethylene) amiloride (HMA)), a C kinase inhibitor (H-7) or
      a calmodulin inhibitor (W-7), or in the absence of extracellular Na+. NE also
      increased [Ca2+]i following the pHi increase, which was abolished in the absence
      of extracellular Na+ or Ca2+. This Ca2+ influx was inhibited by HMA but not by
      diltiazem (10(-5) M). Thus, we conclude that alpha 1-adrenergic stimulation
      enhances Na+/H+ exchange by activation of C kinase, thereby allowing
      intracellular alkalinization, and that subsequent activation of Na+/Ca2+ exchange
      increases Ca2+ influx.

PMID- 1980891
TI  - The effects of dopamine D1 and D2 receptor agonists and antagonists in monkeys
      withdrawn from long-term neuroleptic treatment.
AB  - The effects of dopamine D1 and D2 receptor agonists and antagonists were studied
      in eight Cebus apella monkeys previously treated with haloperidol for two years.
      SKF 81297 (specific D1 receptor agonist) induced oral hyperkinesia of variable
      intensity (P less than 0.01): some of the monkeys developed extreme lip smacking,
      tonque protrusions and licking movements while others developed only slight lip
      movements. A combined treatment of SKF 81297 with LY 171555 (full D2 receptor
      agonist) or SCH 23390 (D1 receptor antagonist) inhibited the oral hyperkinesia
      induced by SKF 81297 (P less than 0.01, P less than 0.02, respectively).
      Raclopride (D2 receptor antagonist) did not statistically change oral
      hyperkinesia (P less than 0.2), although five monkeys showed increased oral
      movements; most of these monkeys had pre-existing hyperkinesia. Treatment with
      SCH 23390 or raclopride resulted in an identical dystonic/cataleptic syndrome.
      SKF 81297 inhibited the dystonia induced by SCH 23390, while it did not
      significantly affect raclopride dystonia. The investigation indicates that oral
      dyskinesia may be related to an imbalance in D1 receptor and D2 receptor
      stimulation in favor of D1 receptors. The question now is whether D1 receptor
      antagonists, which may have antipsychotic potential, will produce tardive
      dyskinesia after long-term use.

PMID- 1980892
TI  - Effects of the alpha 1-adrenoceptor antagonist R-(-)-YM12617 on isolated human
      penile erectile tissue and vas deferens.
AB  - The effects of the selective alpha 1-adrenoceptor antagonist, R-(-)-YM12617 (5-[2
      [[2-(0-ethoxyphenoxy)ethyl]amino] propyl]-2-methoxybenzenesulphonamide HCl), were
      investigated in isolated human corpus spongiosum, corpus cavernosum, and vas
      deferens. R-(-)-YM12617 concentration dependently and competitively inhibited
      contractions induced by noradrenaline in human penile erectile tissue (pA2 value
      in corpus spongiosum = 9.92), and the drug was approximately 12 times more potent
      than prazosin (pA2 value = 8.83). In the vas deferens, R-(-)-YM12617 and prazosin
      inhibited electrically induced contractions concentration dependently, and
      abolished the contractions at 10(-6) and 10(-5) M, respectively. The -log IC50
      values for R-(-)-YM1261 and prazosin were 8.46 and 7.50, respectively. It is
      concluded that R-(-)-YM12617 is a potent inhibitor of alpha 1-adrenoceptors in
      human penile erectile tissues and vas deferens, and that the drug, if injected
      intracavernosally, may be useful for the treatment of penile erectile
      dysfunction.

PMID- 1980893
TI  - New strategies in molecular genetic studies of X-linked retinitis pigmentosa.
AB  - New techniques developed in the past few years are being used to isolate the
      genes responsible for X-linked retinitis pigmentosa. The use of hypervariable
      probes in linkage, the construction of genetic and physical maps, and the search
      for putative gene sequences of interest are described.

PMID- 1980894
TI  - [Structural characterization of the somatostatin receptors on rat cerebrocortical
      membranes].
AB  - We characterized structurally the receptors for somatostatin in rat cerebral
      cortex by affinity labeling with [125I-Tyr1] somatostatin. [125I-Tyr1]
      somatostatin was cross-linked to cerebrocortical membranes using photoreactive
      cross-linker: N-5-azido-2-nitrobenzoyloxy-succinimide. Analysis by
      autoradiography revealed a broad band centered at Mr = 72,000 in the presence or
      absence of dithiothreitol. Affinity labeling of and specific [125I-Tyr1]
      somatostatin binding to cerebrocortical membranes were decreased similarly by
      adding unlabeled somatostatin or nonhydrolyzable guanine nucleotide analogue,
      guanyl-5'-yl imidodiphosphate, in a dose dependent manner. The pretreatment of
      cerebrocortical membranes with islet activating protein resulted in a decrease in
      subsequent affinity labeling of the protein. The cross-linked protein could be
      solubilized with Zwittergent 3-12 and poorly with digitonin, triton X-100 and NP
      40. When exposed to agarose-coupled lectins, the solubilized labeled protein was
      absorbed to wheat germ agglutinin, partially to ricin communis-II, and not to
      concanavalin A or lentil lectin. The Mr = 72,000 protein bound to wheat germ
      agglutinin-agarose was eluted with not only N,N',N"-triacetylchitotriose but also
      N-acetylglucosamine. These results suggest that somatostatin receptors on
      cerebrocortical membranes are a monomeric glycoprotein with a Mr = 70,000
      containing no disulfide-linked binding subunit, which is coupled to islet
      activating protein-sensitive guanine nucleotide regulatory protein.

PMID- 1980895
TI  - Intestinal amino acid transport: an overview.

PMID- 1980896
TI  - Modulation of gamma-glutamyltranspeptidase activity in rat liver plasma membranes
      by thyroid hormone.
AB  - 1. In adult male and female rats, liver plasma membrane gamma
      glutamyltranspeptidase activities were 16-fold higher in the propylthiouracil
      (PTU)-induced hypothyroid state than in the control euthyroid state; thyroxine
      (T4)-replacement resulted in an 80% restoration to control levels. 2. Liver
      plasma membrane gamma-glutamyltranspeptidase activities were 6.7-fold higher in
      PTU-induced congenitally hypothyroid rats than in control euthyroid rats; T4
      replacement reduced enzyme activities to 37% of control levels. 3. In adult rats,
      in response to the development and recovery from tri-iodothyronine (T3) excess,
      liver plasma membrane gamma-glutamyltranspeptidase activities were inversely
      related to, and out of phase by 12 hr, to the earlier changes in T3. 4. Liver
      gamma-glutamyltranspeptidase is a thyroid hormone-dependent enzyme.

PMID- 1980897
TI  - Mechanisms of antibiotic resistance and implications for therapy. Proceedings of
      an international symposium. Rio de Janeiro, 19 April 1988.

PMID- 1980899
TI  - Progress in animal retroviruses. 21st Congress of the International Association
      of Biological Standardization. Annecy, France, 4-6 October 1989.

PMID- 1980898
TI  - Effects of suramin on hormone release by cultured rat anterior pituitary cells.
AB  - Suramin is a polyanionic compound which has been used in the treatment of
      trypanosomiasis and acquired immunodeficiency syndrome (AIDS), while preliminary
      success has been reported in the treatment of cancer. However, suramin also
      causes adrenal insufficiency. We have previously reported that suramin
      selectively inhibited corticotropin (ACTH)-stimulated corticosterone release by
      dispersed adrenal cells in a dose-dependent manner via a direct interaction with
      the ACTH molecule. The present study was undertaken in order to investigate the
      effect of suramin on hormone release by dispersed rat anterior pituitary cells.
      Suramin at a concentration of 100 microM inhibited both basal and secretagogue
      stimulated ACTH release by cells cultured in minimal essential medium (MEM) only,
      while it had no effect on ACTH release by cells cultured in MEM + 10% fetal calf
      serum (FCS) or MEM + 0.1% bovine serum albumin (BSA). In addition, suramin also
      caused a parallel decrease of prolactin (PRL) and growth hormone (GH) release by
      cells cultured in MEM only, suggesting a toxic, rather than a selective effect of
      suramin on anterior pituitary cells cultured in MEM only. In addition, suramin
      potentiated the effect of thyrotropin-releasing hormone (TRH) on PRL release by
      cells cultured in MEM + 10% FCS and suppressed the inhibitory effect of dopamine
      (DA) on PRL release by cells cultured in MEM + 10% FCS and in MEM + 0.1% BSA.
      Comparable suppressive effects of suramin on growth hormone-releasing hormone
      (GHRH)-stimulated and somatostatin (SRIH)-inhibited GH release were found in
      cells cultured in MEM + 0.1% BSA but not in cells cultured in MEM + 10%
      FCS.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1980900
TI  - Asymptomatic feline leukemia virus carrier cats have an enhanced susceptibility
      to feline immunodeficiency virus-induced disease.

PMID- 1980901
TI  - SIVsmm infection of macaque and mangabey monkeys: correlation between in vivo and
      in vitro properties of different isolates.
AB  - Simian immunodeficiency virus from sooty mangabey monkeys (SIVsmm), a lentivirus
      closely related to SIV from macaques and the human immunodeficiency virus type 2
      (HIV-2), is pathogenic for various species of macaques but is nonpathogenic for
      mangabeys. Comparison of in vivo and in vitro responses of macaques and mangabeys
      or their lymphocytes, respectively, to SIVsmm infection indicated that lack of
      disease in mangabeys apparently was not due to effective control of virus
      expression by the immune system because SIVsmm-infected, asymptomatic mangabeys
      have high viral loads. Failure of mangabeys to develop disease may be related to
      the fact that the prototype SIVsmm (SMM-9) replicated in, but was not cytopathic
      for, mangabey CD4+ cells. In contrast, replication of SMM-9 in peripheral blood
      mononuclear cells from pigtailed macaques resulted in specific loss of CD4+ cells
      and induction of an AIDS-like disease. A variant of SMM-9, designated SMM-PBj14,
      was identified, however, that was extremely cytopathic for mangabey CD4+ cells
      and also induced acute lethal disease in both macaques and mangabeys. Acute
      disease was associated with extensive lymphoid hyperplasia, which was correlated
      in vitro with induction of proliferation of PBMC in SMM-PBj14-infected cultures.
      Infectious molecular clones of SMM-PBj14 exhibited the same in vitro and in vivo
      properties as SMM-PBj14. Future analysis of chimeric viruses may lead to the
      identification of specific regions of the viral genome that influence the various
      in vivo and in vitro properties of these SIVsmm isolates.

PMID- 1980902
TI  - Reduction of beta-adrenoceptor function by oxidative stress in the heart.
AB  - The effect of oxidative stress on beta-adrenoceptor function in the heart was
      determined. To this end ventricle membranes, field-stimulated rat left atria and
      field-stimulated rat right ventricle strips were exposed to 0.1 mM cumene
      hydroperoxide for 20 min. It was found that oxidative stress increased beta
      adrenoceptor number and reduced c-AMP formation in the ventricle membranes. In
      the rat left atria and rat right ventricle strips the efficacy of beta
      adrenoceptor agonists was reduced to approximately 30% of the control value,
      whereas maximal beta-adrenoceptor-mediated response was reduced to 50%. Using
      membranes from control atria and from atria exposed to oxidative stress, it was
      found that oxidative stress had no effect on beta-adrenoceptor density, nor on
      the affinity of (-)isoproterenol for the receptor. c-AMP production in membranes
      prepared from atria exposed to oxidative stress was reduced to approximately 30%
      of the c-AMP production in membranes prepared of control atria. In addition, it
      was found that the shape of the function that transduces the stimulus which is
      generated by receptor activation into an effect, is not altered by oxidative
      stress. It was concluded that the reduction of the efficacy of beta-adrenoceptor
      agonists by oxidative stress is probably caused by the reduction of c-AMP
      formation. Because the efficacy of forskolin and of dibutyryl c-AMP was not
      affected by oxidative stress, the reduced c-AMP formation is probably caused by
      an impaired coupling between the receptor and adenylate cyclase. The reduction of
      maximal beta-adrenoceptor-mediated response might be the result of cytotoxic
      aldehydes that are produced during oxidative stress. In ischemia, catecholamine
      release and subsequent beta-adrenoceptor hyperstimulation lead to cardiotoxicity.
      As shown in the present study, oxidative stress reduces beta-adrenoceptor
      function. This might represent a protective physiological feedback mechanism that
      protects the heart against excessive beta-adrenoceptor stimulation.

PMID- 1980903
TI  - Non-adrenergic, non-cholinergic influences on rabbit gastric tone.
AB  - In the rabbit "in vivo", arterial infusions of adenosine 5'-triphosphate (ATP)
      and vasoactive intestinal polypeptide (VIP) not only evoked gastric inhibitory
      motor responses, but influenced the tone of the stomach. ATP increased and VIP
      decreased the gastric tone. The effects on the tone appeared strictly related to
      the inhibitory motility patterns elicited in the stomach by the two non
      adrenergic, non-cholinergic neurotransmitters.

PMID- 1980905
TI  - Fogarty/WHO International Conference on Cellular Mechanisms in Malaria Immunity.
      Bethesda, MD, April 3-6, 1990. Proceedings.

PMID- 1980904
TI  - [Sudden death in psychiatric patients].

PMID- 1980906
TI  - The role of CD4+ T cells in the protective immune response to Plasmodium chabaudi
      in vivo.
AB  - CD4+ T cells are an essential component of the protective immune response to
      Plasmodium chabaudi. In order to determine whether the presence of CD4+ T cells
      is necessary throughout a primary infection for a protective immune response to
      develop mice were depleted of their CD4+ T cells in vivo by treatment with
      specific antibodies. Removal of CD4+ T cells during the acute phase of infection
      renders mice incapable of clearing their infection. In contrast, removal of CD4+
      T cells after this time did not affect their ability to control their
      parasitaemia. The ability to control parasitaemia correlated with appearance of
      malaria-specific IgG antibodies. Our data, therefore, suggest a mechanism
      requiring the presence of CD4+ T cells during the acute pre-IgG period. Later,
      after IgG has been produced, this mechanism is no longer required.

PMID- 1980907
TI  - Cellular mechanisms in immunity to blood stage infection.
AB  - We studied mechanisms of immunity to blood stage infection in the mouse malarias
      Plasmodium vinckei and Plasmodium yoelii 17X. Infection with P. vinckei was
      uniformly lethal, whereas P. yoelii 17X caused a self-limited, nonlethal
      infection. Transfer of immune CD4+ T cells conferred protection against P. yoelii
      in nude mice. Previous studies by others had suggested that immunity to P. yoelii
      may be related to MHC class I expression on reticulocytes and found that CD8+ T
      cells alone transferred protection in immunodeficient mice. However, in our
      experiments, immune CD8+ T cells failed to transfer protection. In the P. vinckei
      system, both B cell-deficient and immunologically intact mice developed immunity
      to P. vinckei after parasite infection and drug cure. In vivo depletion of CD4+ T
      cells abrogated immunity in these immune mice. Adoptive transfer of CD4+ T cells
      failed to protect nude or normal mice from P. vinckei infection, but the transfer
      of immune CD4+ T cells reconstituted immunity in CD4-depleted immune mice.
      Splenectomy of immune mice resulted in the complete loss of immunity. Despite the
      fact that immunity to P. vinckei could be achieved with live parasite infection
      and drug cure, immunization of mice with killed P. vinckei with various adjuvants
      failed to protect mice from live challenge. In contrast, immunization with killed
      P. vinckei antigens in combination with attenuated Salmonella typhimurium SL3235
      induced a high degree of protective immunity. These results suggest that
      induction of immunity against virulent malarias requires both induction of CD4+ T
      cells and certain splenic alterations caused by parasite infection or S.
      typhimurium.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1980908
TI  - Mutations with multiple independent origins in surface antigens mark the targets
      of biological selective pressure.
AB  - This manuscript documents the existence and importance of a small subset of
      mutations in Plasmodium falciparum genes that continually reoccur in separated
      populations. Here we describe how to identify recurrent mutations using a novel
      application of pre-existing computer programs designed to trace genealogy.
      Perhaps the most striking example of this phenomenon occurs in the cytotoxic T
      cell epitope of a malaria surface antigen, the circumsporozoite (CS) protein of
      P. falciparum, where identical sequence types clearly have multiple independent
      origins. The importance of this observation is that it conclusively demonstrates
      selective pressure on these sequences and indicates that there is a significant
      natural mechanism relating to the circumsporozoite protein that affects the
      success of malaria sporozoites.

PMID- 1980909
TI  - Peptide analysis of the T cell response to the malaria circumsporozoite (CS)
      protein.
AB  - The T cell response to the circumsporozoite (CS) protein is still not well
      understood. There is still not agreement on the degree of immunological non
      responsiveness or even on the basic question of whether the response to native CS
      protein requires T cells at all. Recombinant proteins and synthetic peptides are
      tools that are helping us learn the basics of the immune response to this
      protein. Here, the human and murine responses to the protein are probed using
      these valuable research tools. Then, the possibility of using peptide vaccines is
      discussed.

PMID- 1980910
TI  - Hepatic phase of malaria is the target of cellular mechanisms induced by the
      previous and the subsequent stages. A crucial role for liver nonparenchymal
      cells.
AB  - Both the sporozoites and the erythrocytic stages can modulate the hepatic phase
      by cytokines, notably IFN-gamma, TNF and IL-6, either directly or as a result of
      a cascade of events, and by MHC-restricted and antibody-dependent cell-mediated
      cytotoxicity. The role played by CD8+ T cells in inducing protective immunity
      against pre-erythrocytic stages is clearly established. The potential interest of
      triggering peptide-primed CD4+ T cells has to be considered regarding protection.
      Indeed, CD4+ T cells induced by the non-repetitive part of the CS protein of
      Plasmodium yoelii are protective, by eliminating malaria from hepatocytes. The
      crucial role of the liver NPC has to be emphasized, their participation in TNF
      schizonticidal effect and in ADCC mechanisms being strongly supported by our
      data.

PMID- 1980911
TI  - Therapeutic effectiveness and tolerance of 5-aminosalicylic acid in short term
      treatment of patients with ulcerative colitis at a low or medium phase of
      activity.
AB  - The therapeutic effectiveness and tolerance of 5-aminosalicylic acid (5ASA),
      compared with Salazosulphapyridine (SASP) in treatment of ulcerative colitis have
      been evaluated in 86 patients with the disease at a low or medium phase of
      activity. After a treatment of six weeks, an improvement was noted in 63.6%
      (5ASA) and 61.3% (SASP) of these patients. However in no case was a complete
      remission of the disease observed on the basis of endoscopic inspection. In
      patients with pancolitis the improvement was lower (37.5% with 5ASA, 40% with
      SASP). The only side-effect was gastric intolerance, which occurred in 18.1% of
      the 5ASA and in 19% of the SASP patients. In conclusion we can assume that 5ASA
      and SASP largely overlap each other as regards both therapeutic effectiveness and
      occurrence of side-effects.

PMID- 1980912
TI  - Anti-inflammatory properties of a preparation containing low doses of copper,
      gold and silver.
AB  - The efficacy of a drug containing three heavy metals together has been tested in
      adjuvant-induced arthritic rats. Treated rats were injected with 22.8 micrograms
      copper gluconate, 0.2 microgram gold thioglucose and 6.8 micrograms silver
      proteinate each day during a period of 29 days. The drug treatment was found to
      diminish the increases in plasma levels of haptoglobin, ceruloplasmin, PGE2, 6
      keto-PGF1 alpha and copper, the decrease in the iron plasma level induced by
      Freund's adjuvant and the paw swelling. No effect was seen on the plasma levels
      of TXB2, Zn, Se, Mn and Ni. Therefore the simultaneous administration of low
      doses of gold, copper and silver had a real anti-rheumatic property in this
      model. These results should be of interest for the long-term treatment of
      arthritis.

PMID- 1980914
TI  - [Beliefs and hopes in antioxidant therapy. Satellite symposium. Bochum, 21
      September 1990].

PMID- 1980913
TI  - [Regulation of beta receptors--practical consequences for therapy].

PMID- 1980915
TI  - Expression of the multidrug resistance gene in human tumors.
AB  - The expression of MDR1 gene was investigated in human solid tumors with respect
      to adriamycin resistance. Forty fresh human surgical specimens were analyzed by
      RNA dot blot assay for their expression of the human MDR1 gene and by
      immunohistological staining using a monoclonal antibody against P-glycoprotein
      (MDR1 gene product). The MDR1 mRNA level was increased in 11 cases of 40 cancer
      patients, including three rectal cancers, two breast cancers, two gastric
      cancers, one colon cancer, one renal cell carcinoma, one gall bladder cancer and
      one malignant lymphoma of stomach. However, considerable variation of the MDR1
      mRNA level was noted among cancers of a specific type. Immunohistochemical
      studies with the monoclonal antibody were shown to be positive in 18 tumors. In
      all tumors tested, the MDR1 mRNA level and the immunohistochemical analysis
      showed a significant correlation. However, two of five tumors which resisted
      adriamycin treatment were found to be negative in MDR1 transcript, but positive
      in immunohistological analysis. These results indicate that immunohistochemical
      analysis would be more sensitive for detecting P-glycoprotein-expression, and
      that resistance to adriamycin, being multifactorial, can be associated at least,
      in part with the increased amount of MDR1 gene product.

PMID- 1980916
TI  - Immunoreactivities for chromogranin A and B, and secretogranin II in the guinea
      pig endocrine pancreas.
AB  - The chromogranins are acidic proteins present in various endocrine cells and
      organs. They consist of chromogranin A (CgA), chromogranin B (CgB) and
      secretogranin II (SgII). In the pancreas, these proteins or their breakdown
      products are possibly involved in the regulation of pancreatic hormone secretion.
      The guinea-pig endocrine pancreas was now investigated immunohistochemically for
      the presence of the chromogranins in five endocrine cell types. CgA is a regular
      constituent of insulin (B-), pancreatic polypeptide (PP-) and enterochromaffin
      (EC-) cells. In addition, a minority of somatostatin (D-) cells were
      immunoreactive for CgA. CgB immunoreactivities were very faint and exclusively
      observed in B-cells. SgII was found in B- and PP-cells; a faint immunostaining
      for SgII was also seen in a few glucagon (A-) cells. Typically, the densities of
      CgA or SgII immunoreactivities varied among the members of a given cell
      population, e.g. among individual B- or PP-cells. The present findings about the
      heterogeneities of immunoreactivities for the chromogranins are in line with
      findings obtained in pancreatic endocrine cells of other species. The true
      reasons for these heterogeneities are enigmatic. It seems probable, however, that
      the corresponding immunoreactivities depend on the intracellular processing of
      the chromogranins which in turn might be related to the metabolic state of
      endocrine cells. This has to be examined in future by experimental
      investigations.

PMID- 1980918
TI  - Susceptibility to develop celiac disease is primarily associated with HLA-DQ
      alleles.
AB  - We have recently reported that the susceptibility to develop celiac disease (CD)
      seems to be primarily associated to a particular combination of an HLA-DQA1
      (DQA1*0501) and an HLA-DQB1 (DQB1*0201) allele: i.e., a particular DQ alpha/beta
      heterodimer. To investigate whether certain DP alleles might also contribute to
      the genetic susceptibility, DPA1 and DPB1 genes of 94 CD patients and 132 healthy
      controls were examined by probing in vitro amplified DNA with sequence-specific
      oligonucleotide probes corresponding to all hitherto known DPA1 and DPB1 alleles.
      The frequencies of the DPA1*0201 and of the DPB1*0101 alleles were increased in
      CD patients compared to healthy controls (0.31 versus 0.14 and 0.25 versus 0.08,
      respectively). However, these DP alleles were in linkage disequilibrium with CD
      associated DQ alleles in the normal population, and the difference in frequency
      of these DP alleles was no longer significant when CD patients and healthy
      controls carrying the CD-associated DQA1*0501 and DQB1*0201 alleles were
      compared. DQB1*0201 homozygous individuals were overrepresented among DQB1*0201
      positive patients compared to controls. When DQB1*0201 heterozygous patients and
      controls were compared, nearly identical frequencies of the DPA1*0201 and the
      DPB1*0101 alleles were found. Thus, the observed increase of the DPA1*0201 and
      DPB1*0101 alleles among CD patients seems mainly to be caused by linkage
      disequilibrium to the CD-associated DQ alleles.

PMID- 1980917
TI  - Histochemistry of reactive oxygen-species (ROS)-generating oxidases in cutaneous
      and mucous epithelia of laboratory rodents with special reference to xanthine
      oxidase.
AB  - Cutaneous and mucous epithelia of various organs of laboratory rodents were
      analysed histochemically for reactive oxygen species (ROS)-generating oxidases
      using cerium methods. High activities of xanthine oxidase and also superoxide
      dismutase were present in orthokeratotic stratified squamous epithelia of skin,
      lips, esophagus and forestomach and parakeratotic keratinizing stratified
      epithelia of vagina, tongue and penis. Moreover, activity was found in simple
      epithelium of the uterus and intestine of rats, mice and guinea-pigs. Moderate
      activities of monoamine oxidase and D-amino acid oxidase were only seen in
      enterocytes of large and small intestine, whereas alpha-hydroxy acid oxidase
      could not be detected at all. With the use of specific inhibitors for superoxide
      anions-producing xanthine oxidase and H2O2-generating superoxide dismutase it was
      shown that epithelial cells of all studied external and internal surface
      epithelia contain a highly effective xanthine oxidase-superoxide dismutase
      system. It is hypothesized that this system might have a general microbicidal
      function and might play a special role in tumor promotion of the skin.

PMID- 1980919
TI  - Evaluation of HLA-class II identity between unrelated individuals by serological
      typing, DNA-RFLP method, and mixed lymphocyte reaction.
AB  - Seven groups, each consisting of two to nine unrelated HLA-A, -B, and -DR
      serologically identical individuals, were analyzed by DNA-restriction fragment
      length polymorphism (RFLP) and mixed lymphocyte reactions (MLR) in order to
      evaluate HLA-class II identity between unrelated individuals and to assess the
      importance of HLA-class II incompatibilities detected by DNA-RFLP in the
      allogeneic reactions. It is clear that DNA-RFLP represents a powerful typing
      method for HLA-DR, -DQ, and -DP since the combinations of the RFLP band patterns
      define all the serological specificities and most of the cellular specificities
      to give a highly accurate typing. This report shows that an HLA-DP
      incompatibility induces proliferation in primary mixed lymphocyte culture (MLC)
      between unrelated HLA-A, -B, -DR, -DQ, and -DW identical individuals, which may
      suggest the importance of this molecule as a transplantation antigen, especially
      for unrelated bone marrow transplantations. Still, an isolated HLA-DPw4/HLA-DP a
      disparity did not induce any proliferation in MLC. Moreover, our results show
      that DQw7 (w3)/DQw8 (w3) disparity associated with HLA-DR4 represents a
      nonfunctional incompatibility in MLR. The HLA-Dw subtypes of HLA-DR specificities
      can induce a high proliferative response in MLC. The HLA-Dw subtypes of HLA-DR
      specificities can induce a high proliferative response in MLC. Finally, DNA-RFLP
      typing represents a reliable method for the selection of histocompatible donor
      recipient pairs and could potentially reduce many logistic problems and delays in
      live-donor transplantation, especially for unrelated bone marrow transplantation.

PMID- 1980920
TI  - The complexity of DRw6 and DR5 haplotypes in American blacks demonstrated by
      serology, cellular typing, and restriction fragment length polymorphism analysis.
AB  - This study describes the diversity of DRw6 and DR5 haplotypes in the American
      black population using serology, cellular typing, and restriction fragment length
      polymorphism (RFLP) analysis. DRw6 (DRw13 and DRw14) and DR5 (DRw11 and DRw12)
      haplotypes are observed at a high frequency in this population (DRw6: 32%, DR5:
      30%). Many of these haplotypes express undefined HLA-D specificities and unusual
      DQ and DRw52 associations which previously have not been well characterized or
      reported (e.g., DRw13, DQw5, DRw52c, D-; DRw13, DQw2, DRw52a, D-; DRw11, DQw5,
      DRw52c, D-). Serologic analysis of class II alleles in American blacks suggests
      the presence of DRw13, DRw11 and DQw6 allelic variants and demonstrates the
      difficulty in defining DRw6 and DR5 in this population. The class II genes from
      four American black families expressing many of the novel DRw13, DRw14, DRw11,
      and DRw12 haplotypes defined by serology and mixed leukocyte culture were further
      characterized by RFLP analysis. The data presented here along with other
      published data identify at least eight DRw13 haplotypes (DRw13A-DRw13H) in the
      human population. Five of these haplotypes exhibit an undefined HLA-D
      specificity. Three DRw14 haplotypes (DRw14A-DRw14C) and eight DR5 haplotypes
      (DRw11A-DRw11E and DRw12A-DRw12C) were also identified. The novel DRw6 and DR5
      haplotypes observed in American blacks may arise from differences in DRB1, DQA1,
      and DQB1 genes as well as from differences in the combinations of alleles of
      these genes encoded by a haplotype. The serologic and RFLP analyses suggest that
      some DRw13 and DRw11 haplotypes represent transitional steps between DRw13 and
      DRw11 in the evolutionary pathway which generated the DRw52 family.

PMID- 1980922
TI  - International Symposium on Chromatography (CIS'89). Tokyo, October 17-20, 1989.
      Proceedings.

PMID- 1980921
TI  - The HLA-DR beta 16 allogenotype constitutes a risk factor for hypertrophic
      scarring.
AB  - Nineteen patients that had developed hypertrophic scars subsequent to thermal
      injury were typed for HLA class II allogenotypes with the restriction fragment
      length polymorphism technique. A significant association was found with DR beta
      16 (pc = 1.45 x 10(-4); relative risk = 12.25). This finding adds evidence to
      other data suggesting that immunologic phenomena are involved in pathologic
      scarring. Moreover, the results presented here have allowed an identification of
      a genetically determined risk factor for hypertrophic scar formation located in
      the HLA region.

PMID- 1980923
TI  - Antimutagenicity and binding of lactic acid bacteria from a Chinese cheese to
      mutagenic pyrolyzates.
AB  - The microbiological characteristics of Nai Ge Da, a traditional cheese in China,
      was investigated. The lactic acid bacteria species were identified as
      Streptococcus cremoris, Streptococcus lactis ssp. diacetylactis, Streptococcus
      faecalis, and Leuconostoc paramesenteroides, Leuconostoc dextranicum, and
      Leuconostoc mesenteroides. Streptococcus cremoris, and Leuconostoc
      paramesenteroides were the dominant strains. The antimutagenicities and binding
      of strains of S. cremoris and S. lactic ssp. diacetylactis to mutagenic
      pyrolyzates was investigated. The lyophilized cells of strains showed the highest
      inhibitory effect on the 3-amino-1,4-dimethyl-[5H]pyrido[4,3-b] indol (Trp-P-1)
      and 3-amino-1-methyl-[5H]pyrido[4,3-b] indol (Trp-P-2), but many strains had no
      significant inhibition against 2-amino-6-methyldipyrido[1,2-a:3',2'-d] imidazole
      (Glu-P-1). The Trp-P-1 and Trp-P-2 were effectively bound to all bacterial cells,
      but binding of Glu-P-1 to cells was not effective. Among the strains tested, S.
      cremoris C-25 not only indicated highest binding to Trp-P-1 and Trp-P-2, but it
      also it had a 25.36% binding ability with Glu-P-1. When all strains were
      autoclaved for 15 min at 120 degrees C, binding ability to mutagens was reduced
      by 3 to 19%. The decrease of binding ability of S. cremoris C-25 was much less,
      being only 2%. After heating at 80 degrees C for 3 h, the binding ability of all
      strains to mutagenic pyrolyzates was not much different from those of parent
      viable cells.

PMID- 1980924
TI  - [Pathologic and Clinical Biochemistry '90. 18th Congress of the Clinical
      Chemistry and Laboratory Diagnostics Society of the GDR with international
      participation and cooperation with the German Society of Clinical Chemistry and
      the Society for Clinical and Experimental Immunology of the GDR. Halle/Saale, 13.
      15. November 1990].

PMID- 1980925
TI  - Actions of excitatory amino acids on brisk ganglion cells in the cat retina.
AB  - 1. Retinal ganglion cell activity was recorded extracellularly in the intact cat
      eye. We examined the effects of iontophoretically applied glutamate (GLU),
      aspartate (ASP), and the specific agonists kainate (KA), quisqualate (QQ), (RS)
      alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA), and N-methyl-D
      aspartate (NMDA) on the spontaneous and light-driven activity of ganglion cells.
      2. ASP and GLU increased the spontaneous as well as the light-driven activity of
      all brisk cell types. The effects of the two drugs were very similar. The
      activity of most cells remained at a constant increased level during prolonged
      application of these drugs. 3. KA also excited all brisk ganglion cell classes
      and caused effects very similar to those of GLU and ASP but was effective at a
      much lower concentration. In general, brisk ganglion cells responded most
      vigorously to KA application. 4. QQ excited approximately 50% of all ON-X and OFF
      X cells encountered, the other 50% of the X cells and all Y cells were inhibited
      during QQ-application. This inhibition was quite likely due to the stimulation of
      glycinergic and GABAergic interneurons, because it was reduced or abolished
      during application of the respective antagonists strychnine and bicuculline. All
      ganglion cells apparently received either direct or indirect excitatory input
      from QQ receptors, which can be revealed by blocking the inhibitory interneurons.
      5. The major actions of QQ on the discharge rate of ganglion cells are mimicked
      by AMPA. Hence, the actions of QQ are likely to be mediated by the "classical" QQ
      receptor, ion-channel complex rather than by the recently described type of QQ
      receptor that is coupled to a second messenger system. 6. NMDA excited ON-X, OFF
      X, and OFF-Y cells but inhibited ON-Y cells. Excitatory and inhibitory NMDA
      effects could be blocked by the specific NMDA-receptor antagonists D(-)-2-amino-7
      phosphono-heptanoate (AP-7) or 3-((+/-)-2-carboxypiperazin-4-yl)propyl-1
      phosphonic acid (CPP). If the GABAergic transmission was blocked by bicuculline,
      the NMDA-induced inhibition of ON-Y cells was abolished. We conclude that NMDA
      activates GABAergic interneurons that in turn reduce the activity of ON-Y cells.

PMID- 1980926
TI  - The effect of varying stimulus intensity on NMDA-receptor activity in cat visual
      cortex.
AB  - 1. A study was made of the relative contribution of N-methyl-D-aspartate (NMDA)
      and non-NMDA receptors to the visual responses of cells in different layers of
      the cat visual cortex at different levels of excitatory drive (which was varied
      by altering the stimulus contrast). 2. Receptive fields were mapped for 121 cells
      in area 17 of cat cortex. Cells were characterized to determine the optimal
      visual stimulus, the brightness of which was then varied relative to background
      luminance to construct a contrast-response (C-R) curve for each cell. Curves were
      made during control conditions and during application of agonists (NMDA and
      quisqualate) and/or antagonists [(D)-2-amino-5-phosphonovaleric acid (D-APV) and
      6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)] to examine the excitatory amino acid
      components of the visual response. 3. Threshold responses were obtained with
      stimuli between 1/60 and 1.8 X background luminance. The cell response, measured
      by firing rate, was linearly related to stimulus contrast over 1-2 decades and
      saturated at higher contrasts. 4. Application of APV reduced the slope of the
      linear portion of the C-R curve for cells located in layers II and III (average
      reduction, 59% of control). APV did not decrease the threshold to stimulation.
      The "just suprathreshold" responses to stimulation were reduced by the same
      proportion as the saturation responses for individual cells. The principal effect
      was therefore to reduce the gain of the C-R curve in these layers. 5. Application
      of APV reduced the spontaneous activity of cells located in layers IV, V, and VI
      with little if any effect on the gain of the C-R curve. This suggests a tonic
      background level of NMDA-receptor activation in these layers, which is not
      directly related to the visual response. 6. Low levels of NMDA increased the gain
      of the C-R curve in layers II/III and V/VI. On the other hand, low levels of
      quisqualate increased the overall level of firing without affecting the gain of
      the C-R curve. NMDA did not increase the gain of the curve in layer IV. 7. These
      experiments show that visual stimuli that produce just suprathreshold responses
      activate NMDA receptors. The degree of activation is proportionally the same for
      small responses and large responses for an individual cell. Rather than finding a
      threshold for NMDA-receptor activation, a continuous range of NMDA-receptor
      influence was observed over the entire response range.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1980928
TI  - Proceedings of the Tenth World Congress of the International Society for the
      Study of Vulvar Disease, Washington, D.C., October 22-26, 1989.

PMID- 1980927
TI  - Components of field potentials evoked by white matter stimulation in isolated
      slices of primary visual cortex: spatial distributions and synaptic order.
AB  - 1. We have recorded profiles of the spatial distributions of extracellular field
      potentials in transverse slices of rat primary visual cortex. Responses were
      evoked by electrical stimulation near the white matter/layer VI border and
      sampled from layers I to V along the radial axis orthogonal to the laminae and
      intersecting the stimulation site ("on-beam" recording). To assess the activity
      of "horizontal" connections, we also recorded profiles along axes parallel to the
      cortical lamination ("off-beam" recording), usually in layer III. Overall, our
      goal was to extend understanding of the physiology and organization of
      neocortical circuitry and to provide a basis for comparisons of data from
      different experiments and experimenters when neocortical field potentials are
      used in studies of plasticity and pharmacology. 2. Responses were highly specific
      with respect to the cortical layers. We distinguish four major components: two
      kinds of population spike ("S1" and "S2") and two slower waveforms ("W1" and
      "W2"). The latter appear to represent flow of current in apical dendrites of the
      supragranular layers. Component W1, the earliest slow component, is a
      synaptically driven field potential dipole that is positive in layer I and
      negative in layer II. Based on estimates of current source densities (CSDs), we
      attribute this to entry of depolarizing current into dendrites and/or cell somata
      in layer II, ascending intradendritic current, and passive depolarization of
      inactive dendritic membrane in layer I. Component W1 rises during the 20 ms after
      stimulation and falls during the 50-100 ms thereafter. Component W2 is also
      positive in layer I but maximally negative in layer III. It rises for
      approximately 100 ms after stimulation and decays during the following 400-800
      ms. 3. Component S1 does not depend on synaptic transmission because it persists
      during the application of glutamate receptor antagonists or medium that is low in
      Ca2+. This component is largest in layer III, radial to the site of stimulation.
      There, it is a negative deflection, typically 1-2 mV in amplitude and lasting
      roughly 2 ms, with a latency to peak between 2 and 4.5 ms. Component S1 is most
      likely a population spike due to synchronized firing of cell somata activated
      antidromically via unmyelinated efferent axons. 4. Component S2 is a short (less
      than 20 ms) burst of population spikes specifically in layer III. Individual S2
      spikes closely resemble S1 spikes, and we propose that the same neuronal
      population generates both. However, S2 spikes require glutamatergic synaptic
      transmission.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1980929
TI  - Policies for managing hypertensive patients: a survey of the opinions of British
      specialists.
AB  - In September 1988 medically-qualified members of the British Hypertension Society
      were asked to complete anonymously a questionnaire relating to their views on the
      management of hypertensive patients. Of 149 questionnaires posted, 90 were
      returned (60%). There was general agreement that non-pharmacological measures,
      particularly weight loss and alcohol restriction, are effective treatments.
      However, there was wide variation in the minimum level of blood pressure
      considered to warrant drug treatment and little consensus regarding measurement
      policies or target blood pressures. The drugs of first choice were beta-blockers
      (54% in men, 35% in women) and thiazide diuretics (28% in men and 47% in women),
      and they were also the most frequent second choices with 54% of respondents
      advocating 'stepped-care' based on these drugs. The maximum age at which
      respondents would be prepared to introduce antihypertensive drugs varied widely
      although 63% considered that thiazide diuretics are first choice in the elderly.
      These findings demonstrate a broad range of opinion on the management of
      hypertension among British specialists, and suggest a continuing need for large
      clinical trials.

PMID- 1980931
TI  - The role of ACE inhibitors in current clinical practice. The place of
      perindopril: a review. Proceedings of two symposia. 8 November and 15 November,
      1989.

PMID- 1980930
TI  - Alpha-blocker therapy; a possible advance in the treatment of diabetic
      hypertension--results of a cross-over study of doxazosin and atenolol monotherapy
      in hypertensive non-insulin dependent diabetic subjects.
AB  - Hyperglycaemia, a raised fibrinogen, an increased serum triglyceride and a
      reduced HDL-cholesterol are common metabolic features of non-insulin dependent
      diabetes mellitus (NIDDM). Hypertension is frequently associated with NIDDM,
      however the influence of antihypertensive therapy on these combined factors in
      the diabetic is at present unclear. In a double-blind placebo-controlled
      crossover study in 20 stable NIDDM subjects with hypertension, the metabolic
      effects of 6 weeks' treatment with the alpha-blocker, doxazosin, was compared
      with treatment with the beta-blocker, atenolol. Similar and significant
      reductions in BP were produced by both drugs. Significant increases in weight,
      HbA1, apoprotein B, serum triglyceride and cholesterol/HDL ratio were observed
      with atenolol therapy. Doxazosin therapy was associated with opposite patterns of
      changes in fasting glucose, lipids and lipoproteins but only for serum
      triglyceride was difference between treatments significant. Fibrinogen was not
      altered by either treatment. Conclusions from this study indicate; 1) adrenergic
      mechanisms may be an important influence on glucose homeostasis and lipid
      metabolism in NIDDM and 2) the beta-blocker, atenolol, has a small adverse effect
      on weight, glycaemic control and the atherogenic lipid profile, whereas the alpha
      blocker, doxazosin, has no such effect and may, in part, correct the disturbances
      of lipoprotein metabolism characteristic of NIDDM.

PMID- 1980932
TI  - Analysis of eight Sipple's syndrome patients and review of eighty-two cases from
      the Japanese literature.
AB  - Eight Sipple's syndrome patients from four families have been reviewed. One
      family had the largest number of members with pheochromocytoma and/or medullary
      thyroid carcinoma. A total of 82 cases (47 females and 35 males) collected from
      the Japanese literature during the period 1960-1989, are also reviewed. The ages
      ranged from 22 to 73 (median 41) years, 13%, being over the age of 60 years
      (elderly patients). Pheochromocytoma occurred bilaterally in 72% of cases. With
      Sipple's syndrome, a relatively high urinary excretion of the epinephrine
      fraction and a high content of epinephrine in the tumor tissues were thought to
      be characteristic. Seventy-three patients underwent adrenalectomy with a
      successful outcome for 62 (85%). There needs to be careful periodic follow-up
      after unilateral adrenalectomy. Medullary thyroid carcinoma (MTC) also occurred
      bilaterally and was multicentric in 66% of cases, and was often found to be
      metastasized to the cervical lymph nodes at the time of surgery (35%).
      Parathyroid disease was found in 22% of cases: parathyroid adenoma in nine,
      hyperplasia in 10. Fourteen patients (17%) died of surgical complications,
      hypertensive crisis caused by excessive catecholamine release and/or widespread
      MTC metastases.

PMID- 1980933
TI  - [Current principles of the treatment of prolonged QT interval syndrome].

PMID- 1980934
TI  - Treatment of tardive akathisia with clonidine.
AB  - Two cases of tardive akathisia, which were misdiagnosed as anxiety originating
      from a schizophrenic disorder, had been treated with anxiolytics in addition to
      neuroleptics and anticholinergics. The diagnoses were changed to tardive
      akathisia, the anticholinergics were discontinued, and the patients were treated
      with clonidine successfully. In view of the similar effects of clonidine and
      anticholinergics, the pathophysiology of tardive akathisia must be very similar
      to that of tardive dyskinesia.

PMID- 1980935
TI  - Renal ammonia and bicarbonate production in chronic renal failure.
AB  - A characteristic feature of chronic renal failure (CRF) is decreased urinary NH4+
      excretion and an alteration in systemic acid-base balance. In normal humans,
      glutamine is an important precursor of urinary NH4+; however, in CRF, renal
      glutamine extraction is significantly decreased. This finding suggests that
      alternate sources for urinary NH4+ exist. In addition to being an important
      precursor of urinary NH4+, the metabolism of glutamine generates alpha
      ketoglutarate, an important substrate for new renal HCO3- generation in the
      proximal tubule. A useful model of the metabolic derangements in human CRF is the
      subtotally nephrectomized rat. In this review, the ammoniagenic pathways in this
      model of CRF are characterized with an emphasis on the role of glutathione and
      gamma-glutamyltransferase. In addition, recent data are presented on the
      production and partitioning of NH4+ and HCO3- into blood and urine in normal rats
      and rats with CRF.

PMID- 1980936
TI  - Genotype at the P450scc locus determines differences in the amount of P450scc
      protein and maximal testosterone production in mouse Leydig cells.
AB  - A genetic difference in maximal testosterone production in Leydig cells relates
      to differences in the genotype at the P450scc locus. The genetic relationship
      between the P450scc gene, the amount of Leydig cell P450scc protein, and maximal
      testosterone production was determined in the F2 generation of mice derived from
      SWR/J mice (SWR), a high Leydig cell testosterone-producing strain, and from
      C3H/HeJ (C3H), a low Leydig cell testosterone-producing strain. A restriction
      fragment length polymorphism was identified in the P450scc gene between SWR and
      C3H mice. This restriction fragment length polymorphism was used to identify F2
      mice homozygous for the SWR or the C3H alleles of the P450scc gene. The two types
      of homozygous mice were compared with regard to maximal testosterone production
      and the amounts of P450scc, P45017 alpha, and 3 beta-hydroxysteroid dehydrogenase
      isomerase (3 beta HSD) proteins. Maximal testosterone production, amounts of
      P450scc and 3 beta HSD were significantly greater in the SWR than in the C3H
      progenitor mice. In the F2 mice, homozygous for either the SWR or the C3H allele
      of P450scc, the differences in maximal testosterone production and the amount of
      P450scc protein were comparable to the differences in the two progenitor strains.
      A significant correlation (r = 0.75; P less than 0.01) was found between the
      amount of P450scc protein and maximal testosterone production. No differences in
      the amounts of P45017 alpha or 3 beta HSD were observed in the F2 males.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1980937
TI  - Estrogen-dependent effects of bombesin on in vivo growth hormone secretion in the
      rat.
AB  - Previous studies carried out in normal male or ovariectomized female rats have
      shown that bombesin plays an inhibitory role on growth hormone (GH) secretion.
      Since estrogens play an important role in the neuroregulation of GH secretion, we
      have studied the effects of bombesin on basal GH secretion and GH responses to GH
      releasing hormone (GHRH) in untreated and estrogen-treated male rats (200
      micrograms estradiol valerate s.c., 1 single dose 3 days before the experiment or
      every 3 days for 2 weeks). All the experiments were carried out in rats
      anesthetized with pentobarbital. GH responses to GHRH (1 microgram/kg) were
      inhibited by bombesin (100 micrograms/kg) in untreated rats, but were markedly
      increased in rats treated with estrogens either 3 days before or for the previous
      2 weeks. Similarly, bombesin administration (25 or 100 micrograms/kg) in estrogen
      treated rats induced a clear-cut, dose-related increase in basal GH levels. This
      stimulatory effect of bombesin was not affected by passive immunization with
      antisomatostatin antiserum (750 microliters i.v., 60 min before) and only
      partially blocked by anti-rGHRH antiserum (750 microliters i.v., 1 h before). In
      conclusion, our data show that bombesin exerts an inhibitory effect in normal
      male rats but a stimulatory one in estrogenized rats. This latter effect is
      independent of somatostatin and only partially blocked by anti-rGHRH serum.

PMID- 1980938
TI  - Nurses should share experiences in bid to implement Project 2000.

PMID- 1980939
TI  - Application of biotechnology for the diagnosis and control of ticks and tick
      borne diseases.
AB  - Current and potential applications of biotechnology to detect and control
      anaplasmosis, bovine babesiosis, cowdriosis, and theileriosis are examined in the
      light of dramatic advances in molecular biology. Vaccines and the diagnostic use
      of nucleic acid probes, restriction fragment length polymorphisms, and monoclonal
      antibodies are discussed in detail, as are novel genetic methods for increasing
      the resistance of livestock to disease. Strategies are suggested for using
      molecular and non-molecular approaches in integrated programmes for controlling
      haemoparasitic diseases of livestock.

PMID- 1980940
TI  - [Effectiveness of various methods of conservative therapy of cryptorchism in
      boys].

PMID- 1980941
TI  - Centrally administered vasopressin antagonizes pentobarbital-induced narcosis and
      depression of hippocampal cholinergic activity.
AB  - Intracerebroventricular (ICV) microinjection of arginine vasopressin (AVP) to
      pentobarbital-anesthetized rats produced shortening of the duration of narcosis.
      This analeptic effect was blocked by atropine, indicating the central cholinergic
      nature of the response. AVP also increased hippocampal sodium-dependent high
      affinity choline uptake activity that had been depressed by the barbiturate. The
      AVP analeptic effect was blocked by pretreatment with a V-1 (vasopressor), but
      not a V-2 (antidiuretic), vasopressin receptor antagonist. These results suggest
      that ICV AVP produces its analeptic effect by interacting with central V-1
      receptors to activate a hippocampal cholinergic arousal system. The cholinergic
      arousal effect may be a factor in the memory enhancing property of AVP.

PMID- 1980942
TI  - Centrally administered neuropeptide Y enhances the hypothermia induced by
      peripheral administration of adrenoceptor antagonists.
AB  - The distribution of neuropeptide Y in the brain includes extensive coexistence
      within adrenaline- and noradrenaline-containing neurons and many of its actions
      are often associated with adrenergic systems. Since neuropeptide Y
      immunoreactivity is particularly intense in the preoptic area, one of the
      principal sites for thermoregulation, we have tested the effects of neuropeptide
      Y on core temperature in normothermic rats, and rats rendered hypothermic by
      systemic treatment with adrenergic antagonists. In the normothermic rat,
      intracerebroventricular administration of 1 microgram of neuropeptide Y did not
      have a significant effect on core temperature. Intraperitoneal treatment with the
      alpha 1-adrenoceptor antagonist, prazosin, or the beta-adrenoceptor antagonist,
      propranolol, caused an immediate and significant hypothermia; the
      intracerebroventricular administration of 1 microgram of neuropeptide Y, 10
      minutes after these drugs, strongly potentiated their hypothermic effect.
      Although intraperitoneal treatment with the alpha 2-adrenoceptor antagonist,
      idazoxan, had no hypothermic effect per se, the intracerebroventricular
      administration of NPY 10 minutes after this antagonist led to a significant
      decrease in core temperature.

PMID- 1980943
TI  - Synthesis, biochemical and pharmacological properties of BUBUC, a highly
      selective and systemically active agonist for in vivo studies of delta-opioid
      receptors.
AB  - Based on the results of conformational studies of linear and cyclic delta-opioid
      peptides such as BUBU [Tyr-D-Ser(OtBu)-Gly-Phe-Leu-Thr(OtBu)] and DPLPE c[Tyr-D
      Pen-Gly-Phe-Pen], a new enkephalin-related peptide, Tyr-D-Cys(StBu)-Gly-Phe-Leu
      Thr(OtBu) (BUBUC) was synthesized and tested for its opioid activity and
      selectivity at both the peripheral and central levels. Amongst all the synthetic
      compounds described so far, BUBUC appears to be the most highly delta-selective
      probe [KI (mu) = to 2980 nM, KI (delta): 2.9 nM, KI (mu)/KI (delta) approximately
      1000]. This selectivity was confirmed by the results of pharmacological studies,
      including measurements of supraspinal analgesia and behavioral changes in mice.
      In the later test, BUBUC was shown to increase the rearing activity after IV
      administration at very low concentrations (0.1 mg/kg) and this effect was
      reversed by the delta-selective antagonist naltrindole. No antinociceptive
      response was observed at a 10-fold higher concentration. Thanks to its enzymatic
      stability and its hydrophobicity. BUBUC is the first systemically active, highly
      selective delta agonist and should therefore be useful to characterize the
      physiological role of delta-opioid receptors.

PMID- 1980944
TI  - Does prostacyclin affect transmitter release at the mouse neuromuscular junction?

PMID- 1980945
TI  - The guinea pig myenteric plexus as a tool to characterize drugs active at the
      glycine recognition site of the NMDA receptors.

PMID- 1980946
TI  - Central nervous system (CNS) modulation of immune system development: role of the
      thymic beta 2-adrenergic receptor.

PMID- 1980947
TI  - Brain dysfunction and the immune system: lymphocyte's beta-adrenergic receptor in
      Down syndrome.

PMID- 1980948
TI  - Role of D1 and D2 receptors in the regulation of intraocular pressure.

PMID- 1980949
TI  - Ions and intracellular mechanisms involved in the effects of L-glutamate on
      arginine vasopressin release: in vitro researches on rat neurohypophysis.

PMID- 1980951
TI  - Prevalence and severity of dementia. 5th Congress of the International Federation
      of Psychiatric Epidemiology. June 6-8, 1990, Montreal, Quebec, Canada.

PMID- 1980950
TI  - Dystrophin protein and RFLP analysis for fetal diagnosis and carrier confirmation
      of Duchenne muscular dystrophy.
AB  - A pregnant woman with indeterminate Duchenne muscular dystrophy (DMD) carrier
      status, but with DMD diagnosed in her deceased brother (unavailable for study),
      presented for prenatal diagnosis, intending to continue the pregnancy only if
      proven unaffected with DMD with near absolute certainty. Creatine kinase (CK)
      assays to clarify carrier status were inconclusive. Male sex in the fetus was
      identified, but DNA restriction fragment length polymorphism (RFLP) analysis was
      not yet available to this centre to investigate the possible transmission of the
      DMD gene, and the pregnancy was terminated. Tissue histology and dystrophin
      protein analysis demonstrated the absence of DMD. In a situation with proven
      maternal carrier status, future fetal inheritance of the opposite maternal X
      chromosome would indicate the presence of DMD. However, maternal carrier status
      remained in doubt through a second pregnancy, even with RFLP studies, and was
      finally established when dystrophin analysis confirmed the presence of DMD in the
      second fetus. Histologic findings are presented, contrasting features in the two
      fetuses. The value of dystrophin analysis for establishing the diagnosis of fetal
      DMD, in this case proving maternal carrier status in a difficult situation, and
      for demonstrating DMD gene:RFLP haplotype relationships is illustrated.

PMID- 1980952
TI  - Subgroups in Alzheimer's disease: fact or fiction?
AB  - Alzheimer's disease, which accounts for the majority of all dementing disorders,
      presents with a wide spectrum of demographic, neuropsychological, pathological
      and biochemical characteristics. It has become increasingly clear that
      Alzheimer's disease is indeed heterogeneous and lack of success in symptomatic
      treatment may be in part related to this. In an attempt to evaluate the utility
      of possible subgrouping schemas, we reviewed current criteria used to subclassify
      patients with Alzheimer's disease. Results suggest that although treatment
      attempts may have to take a more individualized approach, most current
      subgrouping concepts will probably have limited therapeutic utility.

PMID- 1980953
TI  - Cognitive dysfunction in schizophrenia followed up over 5 years, and its
      longitudinal relationship to the emergence of tardive dyskinesia.
AB  - In this study, 51 chronic schizophrenic in-patients were evaluated for a range of
      demographic, clinical and medication variables, and followed up over five years.
      There was no significant overall change in cognitive function in this patient
      group as a whole, suggesting the absence of active disease at this stage of the
      illness. The only correlate of individual instances of cognitive deterioration
      over the study period was the emergence of new cases of tardive buccal-lingual
      masticatory but not of limb-truncal dyskinesia, and the greater severity of such
      movement disorder. A positive family history was also identified prospectively as
      a predictor of the emergence of tardive dyskinesia in chronic schizophrenia.

PMID- 1980954
TI  - Subjective utility ratings of neuroleptics in treating schizophrenia.
AB  - This study developed a method for measuring subjective costs and benefits of
      psychiatric treatments. Forty-one patients rates the relative bothersomeness of
      symptoms of schizophrenia and side effects of neuroleptics. Thirty-four
      psychiatrists made parallel ratings from the perspective of the average patient
      (individual utility) and of the patient's family and society (institutional
      utility). Psychiatrists predicted patients' ratings moderately well, but
      misjudged the bothersomeness to patients of 24% of side effects and 20% of
      symptoms. When considering the patient's perspective, both schizophrenic patients
      and psychiatrists rated symptoms as no more bothersome than side effects.
      However, psychiatrists saw side effects as significantly less bothersome than
      symptoms when considering costs to society. The subjective utility of neuroleptic
      medications for schizophrenia is most justifiable from an institutional
      perspective.

PMID- 1980955
TI  - [Effect of somatostatin on the digestive tract functions].

PMID- 1980957
TI  - Genetic analysis of the transfer region of the IncN plasmid N3.
AB  - Using lambda::Tn5 insertion mutagenesis and screening for conjugation, the
      boundaries of the IncN plasmid N3 transfer region were determined. Sensitivity to
      phage IKe infection was used to monitor that part of the N3 transfer region which
      harbours genes for pilus synthesis and assembly. We cloned this region, creating
      plasmid pBG21. Escherichia coli cells transformed with pBG21 became sensitive to
      phage IKe and produced pili, as shown by electron microscopy. Various plasmid
      constructions containing parts of the pilus-encoding region were used for
      expression in a minicell system and for expression in an in vitro translation
      system, thus characterizing for the first time some of the gene products of
      domain I (Winans and Walker, 1985a) of the transfer region.

PMID- 1980956
TI  - Tissue distribution and cytofluorometric analysis of oral mucosal T cells in the
      BALB/c mouse.
AB  - The incidence and distribution of Thy-1.2+, Lyt-2.2+ and L3T4+ cells in the
      murine oral mucosa were investigated using qualitative and quantitative
      approaches. From immunostaining of frozen tissue sections, it appeared that the
      majority of oral T cells are located either in the epithelium or within the minor
      salivary gland network. The occurrence of Thy-1.2+, L3T4+ and Lyt-2.2+ cells at
      these sites points to two strategic lines of defence in the event of mucosal
      infections or aggression. A quantitative analysis of oral T-cell subsets was made
      possible by optimizing an enzymatic digestion procedure which preserves all three
      T-cell surface markers. Flow cytometric analysis of oral mucosal cells
      demonstrated that the helper phenotype is about twice as numerous as the
      cytotoxic/suppressor phenotype in the mucosa. Furthermore, in single cell
      suspensions, virtually all Thy-1+ cells were either L3T4+ or Lyt-2.2+ in the
      mucosa and in the spleen. From this frequency analysis and our previous studies,
      we conclude that T cells are a major component of the oral immune system, being 2
      3 times as numerous as B cells or macrophages. Present data on the spatial
      distribution and characteristic ratio of T-cell subsets assess the basal activity
      of the local T-cell populations in healthy animals and lay the basis for
      comparative studies of both qualitative and quantitative variations occurring
      during mucosal infections or autoimmune reactions.

PMID- 1980958
TI  - Clostridium bifermentans serovar malaysia: sporulation, biogenesis of inclusion
      bodies and larvicidal effect on mosquito.
AB  - Sporulation of Clostridium bifermentans serovar malaysia, which has a larvicidal
      activity towards mosquitoes, was examined by electron microscopy. Parasporal
      inclusion bodies lacking a crystalline structure were first detected at t5 (5 h
      after the end of exponentional growth). Also, the presence of "brush-bottle"-like
      appendages appearing first at t5 was noted; these remained attached to the spores
      when released after sporangium lysis. Larvicidal activity assayed on Anopheles
      stephensi larvae appeared at t0 and increased rapidly to a maximum between t5 and
      t8. However, a decrease in bacterial toxicity occurred with sporangium lysis.

PMID- 1980959
TI  - Molecular analysis of human bladder cancer.

PMID- 1980960
TI  - Orthodontic soldering on the model.

PMID- 1980961
TI  - Use of beta 2-adrenergic drugs in obstructive respiratory tract diseases of
      childhood.
AB  - The chemical structure and clinical application of beta 2-mimetic drugs used
      currently in obstructive respiratory tract diseases of childhood have been
      discussed. It has been pointed out that these drugs may be used as
      bronchodilators in manifesting obstruction and as prophylactic agents in chronic
      forms of such obstructive diseases. The aerosol forms of these compounds are the
      most effective but this route of administration meets some technical difficulties
      and cannot be used in children younger than 5-6 years. In the treatment of this
      age group, besides the tablet and elixir forms, the aerosol inhalation is the
      most useful. Selective slow-release beta 2-mimetics introduced about 25 years ago
      are successfully used in form of monotherapy or combination therapy in
      respiratory tract obstructions.

PMID- 1980963
TI  - [The use of beta-blockers in acute myocardial infarct].

PMID- 1980964
TI  - [Symposium: Parkinson disease. Current aspects of diagnosis and therapy.
      Abstracts].

PMID- 1980962
TI  - A preliminary study on the effects of atropine sulphate on bradycardia and heart
      blocks during romifidine sedation in the horse.
AB  - Romifidine (STH 2130-Cl or Sedivet) is an alpha 2-agonistic imino-imidazol
      sedative for intravenous use in horses recently developed by Boehringer
      Ingelheim, Vetmedica GmbH. An exploratory study was done in nine warm-blood
      horses, randomly divided into three groups, which received different dosages of
      romifidine (0.04, 0.08 and 0.12 mg/kg of body weight (BWT) intravenously (i.v.))
      with at least one week's interval between tests. Romifidine induced a marked
      bradycardia accompanied by second degree atrioventricular (AV) block and some
      sinus blocks at all tested dosages. A placebo (NaCl 0.9% i.v.) given 5 min before
      and after romifidine did not affect the cardiac disturbances induced by
      romifidine. A low dose of atropine sulphate (0.005 mg/kg of BWT i.v.) given 5 min
      before romifidine counteracted the bradycardia and caused a normal to increased
      heart rhythm at all romifidine dosages. A higher dose of atropine sulphate (0.01
      mg/kg of BWT i.v.) administered 5 min before sedation induced a tachycardia
      (average 70 beats/min) at all romifidine dosages and completely prevented the
      bradycardia and the heart blocks. The positive chronotrope effects of atropine
      sulphate were attenuated by increasing doses of romifidine. The effects of
      atropine sulphate (low or high doses) given 5 min after romifidine only appeared
      after 5 min. Both dosages counteracted the bradycardia and suppressed the heart
      blocks. No atropine-dependent side effects were observed in non-fasted horses.
      The degree of the romifidine induced sedation was not affected by the use of
      atropine sulphate given before or after romifidine.

PMID- 1980965
TI  - [Alcohol and various occupational medicine aspects].
AB  - Alcohol related laboratory parameters had been taken from 407 employees (336
      males, 71 females) aged 18-65 years on occasion of the annual occupational health
      survey 1989. In relation to anamnesis, drinking habits and medical findings gamma
      glutamyl transpeptidase (gamma-GT) and mean corpuscular volume (MCV) of
      erythrocytes had been used as markers. Signs of alcohol overconsumption could be
      seen in 2.8% of the females and in 16.3% of the males, 6.2% of the latter showing
      somatically complicated abuse. Alcohol dependence was found in 2.1% of the
      females. In addition 33 employees of a malt factory obtaining an allowance of 2l
      beer a day had been investigated; 12.1% proved addicts; 9.1% were found to be
      medically relevant abusers with somatic complications. MCV and gamma-GT turned
      out to be useful criteria pointing at alcohol overconsumption when used in
      coherence with anamnesis and medical examination. These parameters are to be
      obtained by the works' medical officer easily. The importance of those problems
      concerning the medical check-up for certain occupations is pointed out and the
      necessity of different means of medical care as well.

PMID- 1980966
TI  - [Disorders of neurohumoral regulation of functions of the immune system].

PMID- 1980967
TI  - Production, circulation, and excretion of melanin-related metabolites in B16
      melanoma-bearing mice.
AB  - Urinary 5-S-cysteinyldopa (5-S-CD) has been used as a biochemical marker of
      melanoma metastasis. A method was developed for determining the eumelanin-related
      metabolites 5(6)-hydroxy-6(5)-methyoxyindole-2-carboxylic acids (5H6MI2C and
      6H5MI2C) in small volumes of serum. We compared these indoles and 5-S-CD
      regarding the correlation of their production in melanoma, circulation in blood,
      and excretion in urine, with the weight of highly pigmented, B16 mouse melanoma.
      An excellent correlation was found between the serum concentration of 5H6MI2C +
      6H5MI2C (r = 0.92) and 5-S-CD (r = 0.89) and tumor weight. However, the urinary
      excretion of 5H6MI2C + 6H5MI2C and 5-S-CD did not show any significant
      correlation. These results suggest that 5H6MI2C + 6H5MI2C and 5-S-CD in serum may
      better reflect melanoma progression than those in urine. Furthermore, comparison
      of the contents of these melanin-related metabolites between highly pigmented and
      less pigmented B16 melanomas suggests that 5-S-CD may be accumulated in pigmented
      melanoma by virtue of binding to melanin and that catechol-O-methyltransferase
      (COMT) may play a regulatory role in pigmentation.

PMID- 1980968
TI  - 5-S-cysteinyldopac in human urine.
AB  - 5-S-Cysteinyldopac, a compound hitherto demonstrated only in brain tissue, has
      been isolated and quantified in urine. The urines from 12 individuals were found
      to contain 20 +/- 9.1 micrograms 5-S-cysteinyldopac/24 hours. Incubation of 5-S
      cysteinyldopamine with MAO-containing tissue did not give any formation of 5-S
      cysteinyldopac, indicating that this compound is formed by nucleophilic addition
      of cysteine directly to dopac. The findings give further evidence for a small but
      significant non-specific oxidation of endogenous catechol derivatives in vivo, a
      fact to be considered when using 5-S-cysteinyldopa as a measure of pigment
      metabolism.

PMID- 1980969
TI  - Possible formation of cutaneous amyloid from degenerative collagen fibers.
      Ultrastructural collagen changes and the immunoreactivity of cutaneous
      amyloidosis employing anti-type I, III, IV, V collagen antibodies.
AB  - The origins of primary cutaneous amyloid have been investigated and several
      possibilities are proposed. We investigated here several cases by electron
      microscopy and found in all cases characteristic filamentous changes which were
      identical with amyloid structures in the collagen bundles. These observations
      suggested a possible pathway of cutaneous amyloid formation from degenerative
      collagen fibers. Further studies were performed using immunoelectron
      microscopical and immunohistochemical methods employing a panel of anti-collagen
      antibodies to examine the reactivity of amyloid to them. Our results were much
      more suggestive of the collagen origin of this kind of amyloid.

PMID- 1980970
TI  - The distribution of Fc gamma RI, Fc gamma RII and Fc gamma R III on Langerhans'
      cells and keratinocytes in normal skin.
AB  - The distribution of Fc-receptors for IgG (FcR) on human epidermal cells (EC) was
      characterized in situ using monoclonal antibodies (MoAbs) by indirect
      immunofluorescence staining of cryosections. The results showed heterogeneity of
      FcR expression on Langerhans' cells (LC) and keratinocytes (KC). The MoAb IV.3
      against FcR II (CDw32) gave granular staining of most LC whereas the MoAb 32.2
      against FcR I (CD64) occasionally stained a few dendritic cells. 32.2
      demonstrated weak granular staining along the outer aspect of KC in stratum
      spinosum and stratum basale and intense staining of stratum corneum and stratum
      granulosum. The MoAbs Leu 11b against FcR III (CD16) and B1D6 reacting with a
      placental FcR with low affinity for IgG gave intense linear membrane staining of
      KC. Leu 11b produced strongest staining of stratum granulosum and B1D6 the
      strongest staining of stratum spinosum and basale. The results confirm our
      previous observations of FcR in situ on LC and KC in normal skin using functional
      assays and demonstrate that these EC possess different types of low affinity FcR.
      The data support the contention of an immune function of KC. FcR may be mediators
      for interaction between KC and LC. The FcR activity in stratum granulosum may
      have an immune function as a barrier against microorganisms and other antigens.

PMID- 1980971
TI  - Interleukin-1 decreases the number of Ia+ epidermal dendritic cells but increases
      their expression of Ia antigen.
AB  - It is generally accepted that ETAF/IL-1 is produced in epidermis by both
      keratinocytes and Langerhans' cells. We have studied the density and morphology
      of Ia+ epidermal dendritic cells in mice after systemic or intracutaneous
      injection of recombinant IL-1 beta. We found that rIL-1 beta decreased the
      density of Ia+ dendritic cells in the time period 2-7 days after rIL-1 beta
      administration. However, the remaining dendritic cells were enlarged and more
      arborized with increased expression of Ia antigen 1-4 days after injection of rIL
      1 beta. The implication of the results is that ETAF/IL-1 modulates the function
      of Langerhans' cells through autocrine and paracrine regulation.

PMID- 1980973
TI  - In vivo hydration and water-retention capacity of stratum corneum in clinically
      uninvolved skin in atopic and psoriatic patients.
AB  - Hydration and the water-retention capacity of stratum corneum have been
      investigated in uninvolved psoriatic and atopic skin and compared with that of
      healthy controls. Thirty-three subjects of either sex and matched for age entered
      the study. The subjects were free from all signs of skin disease and skin
      dryness. Hydration was evaluated by means of transepidermal water loss and skin
      capacitance measurements. Water-retention capacity was investigated using the
      plastic occlusion stress test. Atopic skin differed significantly from uninvolved
      psoriatic and control skin which had a reduced water content and an increased
      transepidermal water loss. Furthermore, the skin surface water loss profile
      representing the stratum corneum water-retention capacity was significantly lower
      in normal atopic skin. The data suggest that clinically normal skin may be
      functionally abnormal, resulting in a defective barrier that could lead to higher
      risk of irritant or contact dermatitis.

PMID- 1980972
TI  - Interleukin-1 release from peripheral blood monocytes and soluble interleukin-2
      and CD8 receptors in serum from patients with atopic dermatitis.
AB  - In 31 adult patients with atopic dermatitis, the capacity to secrete interleukin
      1 (IL-1) from peripheral blood mononuclear cells and from purified monocytes was
      investigated following stimulation with lipopolysaccharide. We also measured
      soluble interleukin-2 receptor levels (sIL-2R) and CD-8 receptor in serum from
      some of the patients in order to estimate the degree of lymphocyte stimulation in
      vivo. We observed that purified monocytes from patients with atopic dermatitis
      released more IL-1 than unseparated blood mononuclear cells did and also had
      significantly greater IL-1 activity than non-atopic donors. Addition of histamine
      in concentrations of 10(-7) to 10(-4) M did not suppress, but rather augmented
      the IL-1 activity release. An increased monocyte-IL-1 release could lead to
      increased T lymphocyte activity. We observed that 60% of the patients had
      increased sIL-2R concentrations in serum. There was no correlation between serum
      IgE and sIL-2R. Our observations indicate that monocytes in atopic dermatitis
      patients release increased quantities of IL-1, supporting an augmented T
      lymphocyte activation in the patients.

PMID- 1980974
TI  - Herpes simplex virus antigens and inflammatory cells in oral lesions in recurrent
      erythema multiforme. Immunoperoxidase and autoradiographic studies.
AB  - Herpes simplex virus (HSV) antigens were sought in 15 biopsy specimens from both
      lesional mucosa and clinically healthy looking oral mucosa between attacks in
      patients with erythema multiforme (EM). Four of the eight biopsy specimens
      obtained from lesional EM mucosa stained positively with HSV-1-and/or HSV-2
      specific antisera applied in direct immunoperoxidase staining. Of the 16 tissue
      specimens used as controls, two displayed positive staining with HSV-1 and/or HSV
      2. Five of the seven biopsy specimens from macroscopically healthy oral mucosa
      obtained between attacks from patients with recurrent EM stained positively with
      HSV-1 and/or HSV-2. Of the six tissue specimens used as controls, three stained
      positively. Most of the local inflammatory mononuclear cells belonged to the T
      cell series, mainly to the CD-4 subset. A small proportion of the local T cells
      were blast transformed as assessed by CD-25 expression and [3H]thymidine
      incorporation. This, together with the findings showing a lower degree of
      activation in the biopsy from macroscopically healthy looking mucosa between
      attacks suggest an active role of the cell-mediated immune response in the
      genesis of oral lesions in EM. The persistence of HSV antigens, and the well
      established role of HSV as a precipitating factor in recurrent EM, suggest that
      HSV may be involved, but since HSV seems to be present in other mucosal lesions
      as well as in clinically healthy mucosa, quite frequently an additional, hitherto
      unknown factor must be present in order that EM may occur.

PMID- 1980976
TI  - Nickel in nails, hair and plasma from nickel-hypersensitive women.
AB  - The concentrations of nickel in finger-nails, toe-nails, hair and plasma from 71
      nickel-hypersensitive women and 20 non-hypersensitive women were determined.
      Nickel concentrations in finger-nails were significantly higher than in toe-nails
      in both the nickel-hypersensitive group and the control group. Nickel-sensitive
      women had significantly higher levels of nickel in toe-nails, hair and plasma
      than had control subjects, whereas there was no significant difference in nickel
      concentration in finger-nails between the two groups. No correlation could be
      demonstrated between nickel levels in any combination of nails, hair and plasma
      in the nickel-hypersensitive or in the control group.

PMID- 1980975
TI  - A transmission electron microscopical study of dysplastic naevi.
AB  - In this study those features of naevi that fulfil the clinical and light
      microscopical criteria of dysplastic naevi have been further examined with
      transmission electron microscopy. The results have been compared with the
      structure of normal control skin and compound naevi. In dysplastic naevi most
      melanosomes were abnormal, with spherical melansomes, an incomplete inner
      structure and uneven melanin deposit, cigar-shaped melanosomes and
      macromelanosomes. The intraepidermal border between the nests of dysplastic naevi
      were uneven and the dysplastic melanocytes extended their cell bodies among
      surrounding keratinocytes with a tendency to invade the epidermis in an upward
      direction. These findings will serve as additional criteria for dysplastic naevi.

PMID- 1980977
TI  - Use of alternative medicine by patients with atopic dermatitis and psoriasis.
AB  - In a questionnaire study at a university hospital in Norway, 227 of 444 patients
      with atopic dermatitis (51.1%) and 215 of 506 patients with psoriasis (42.5%)
      reported previous or current use of one or more forms of alternative medicine.
      Homoeopathy, health food preparations and herbal remedies were used most. Use was
      related to disease duration, disease severity and--among the atopic dermatitis
      patients--the inefficacy of therapy prescribed by physicians, as judged by the
      patients. The use of alternative medicine is commonplace and should be of concern
      to dermatologists.

PMID- 1980978
TI  - Alternative therapy for atopic dermatitis and psoriasis: patient-reported
      motivation, information source and effect.
AB  - In a questionnaire study, 227 patients with atopic dermatitis and 215 with
      psoriasis, who had used alternative medicine, were asked to state their main
      reason for trying alternative medicine. The answers indicated that the absence of
      satisfactory effect of physician-provided therapy was the most decisive factor.
      Their main information sources on alternative therapies were persons without skin
      disease, and the mass media. The majority reported no improvement, or even
      aggravation of their skin disease, as a result of alternative treatments (except
      for diet changes). These findings emphasize the need for documentation of effect
      of alternative medicine, as well as for further research and education efforts in
      order to improve therapy for atopic dermatitis and psoriasis.

PMID- 1980980
TI  - Patients with mood depression have a high prevalence of seborrhoeic dermatitis.
AB  - Prevalence and severity of seborrhoeic dermatitis were studied in 150 patients
      with psychiatric disorders, including schizophrenia, mood disorders, anxiety and
      organic mental illness. As a control group, we examined 150 patients waiting for
      surgery and regarded as obviously anxious. Thirty-eight psychiatric patients were
      found to have seborrhoeic dermatitis, versus 13 in the surgery group. This
      statistically significant difference was entirely ascribable to patients with
      depression.

PMID- 1980979
TI  - Differences in the skin surface pH and bacterial microflora due to the long-term
      application of synthetic detergent preparations of pH 5.5 and pH 7.0. Results of
      a crossover trial in healthy volunteers.
AB  - Skin cleansing preparations consisting of identical synthetic detergents but
      differing in pH-value (pH 5.5 and 7.0) were applied twice daily on the forehead
      and forearm of healthy volunteers in a randomized crossover trial. The skin
      surface pH was found to be significantly higher when the neutral preparation had
      been used, as was the propionibacterial count (p less than 0.05). The number of
      propionibacteria was significantly linked to the skin pH. Hence even minor
      differences in the pH of skin cleansing preparations seem to be of importance for
      the integrity of the skin surface. This should be taken into account when
      planning the formulation of optimal skin care products.

PMID- 1980981
TI  - The effect of clobetasol-17-propionate and crude coal tar on dithranol-induced
      inflammation. A clinical and biochemical study.
AB  - Clobetasol-17-propionate (CP) and crude coal tar (CT) have an anti-inflammatory
      potential. Both agents have been advocated to suppress irritation of the skin
      during dithranol treatment. The effect of CP and CT on dithranol-induced
      irritation was studied by the assessment of erythema and measurement of alkaline
      phosphatase (ALP) as a direct reflection of the metabolic activity of the
      endothelial cells. Dithranol was applied for 2 h in the relatively high
      concentration of 10%, which resulted in a marked inflammation of the skin in all
      volunteers. Neither CP nor CT influenced the erythema. In contrast, CP and CT had
      a synergistic effect on the dithranol-induced induction of ALP. In conclusion,
      the present study indicates that CP and CT are not indicated for the treatment of
      dithranol-induced irritation.

PMID- 1980982
TI  - Increased subcutaneous adipose tissue blood flow in UVB-inflamed human skin. The
      existence of a cutaneous-subcutaneous reflex mechanism?
AB  - In 4 healthy subjects a skin area 10 mm in diameter was exposed to twice the
      minimal erythema dose of UVB. Subcutaneous blood flow (SBF) in the area was
      measured by the local 133-Xenon washout technique before and 8, 24, 48 and 72 h
      after induction of inflammation. Local skin temperature (TS) was monitored with
      electrical thermocouples. SBF gradually increased by 400% and peaked 24 to 48 h
      after induction of inflammation, while TS peaked after 8 h (+3 degrees C). The
      disparity in skin temperature and subcutaneous blood flow indicates that TS is
      not the governing factor in the increase in SBF. As release of inflammatory
      mediators from the cutis influencing the subcutis and a local effect of UVB on
      subcutis are unlikely, we suggest the existence of a cutaneous-subcutaneous
      vascular reflex mechanism as an explanation for the increased subcutaneous blood
      flow.

PMID- 1980983
TI  - Analysis of lithogenous factors in lichen planus.
AB  - A search for possible lithogenous factors was under-taken in a group of 42 lichen
      planus (LP) patients (15 with urolithiasis and 27 without). Normal mean values of
      calcium, phosphorus, uric acid and creatinine were found in the serum and in the
      24-hour urine collection. However, 9 patients (21%) manifested laboratory
      deviations consisting of hyperuricemia, hyperuricosuria or hypercalciuria, or
      combinations of the three. The prevalence of hyperuricemia among LP patients was
      greater than in matched controls and vis-a-vis the recorded prevalence of
      hyperuricemia in the general population and in other calcium stone formers. These
      findings may suggest involvement of metabolic defects in LP.

PMID- 1980984
TI  - Psoriasis and polyneuropathy. Three case histories.
AB  - Neurophysiological examination of 3 psoriasis patients with symptoms of
      polyneuropathy revealed varying degrees of both sensory and motor nerve affection
      and indicated nerve fibre loss as well as demyelination. Previous reports have
      suggested a connection between peripheral nerves and psoriasis.

PMID- 1980985
TI  - Penetration and enrichment of flufenamic acid in calf skin from patients with
      stasis dermatitis.
AB  - To investigate the hypothesis that the application of medicaments to skin from
      the lower leg of patients with stasis dermatitis might lead to their enhanced
      enrichment, compared with uninvolved skin from the same region, a penetration
      study was performed with flufenamic acid. In 5 patients with pronounced changes
      of chronic venous insufficiency and in 5 control patients without chronic venous
      insufficiency the flufenamic acid content in skin sections parallel to the
      surface was determined by HPLC. In chronic venous insufficiency-skin, the
      flufenamic acid concentration was higher in all skin levels compared to control
      skin. This enrichment of the substance could lead to a prolonged and more intense
      contact with antigen-presenting cells in this region, thus promoting the
      development of contact allergies observed so frequently in this pathologic
      condition.

PMID- 1980986
TI  - Lysozyme and IgA values in patients with atopic dermatitis.
AB  - Ten patients with atopic dermatitis had significantly depressed lysozyme levels
      in saliva, compared with controls, whereas no differences were found in lysozyme
      activity in serum of patients and controls. The concentrations of IgA in saliva
      of patients with atopic dermatitis were also significantly lower than in
      controls, whereas IgA in patients' serum was within normal levels.

PMID- 1980987
TI  - Darier's disease with involvement of both submandibular glands.
AB  - Salivary gland obstruction in association with Darier's disease is described.
      Histological examination of both submandibular glands revealed squamous
      metaplasia of the ducts with suprabasal cleft formation and occlusion of the
      lumen.

PMID- 1980988
TI  - Notalgia paresthetica--puzzling posterior pigmented pruritic patch. Report on two
      cases.

PMID- 1980989
TI  - Generalized morphea with blisters. A case report.
AB  - A patient suffering from generalized morphea developed blisters in the morpheic
      plaques on her buttocks. The plaques had an increased concentration of serum
      aminoterminal propertice of type III procollagen, an echo response and thickened
      skin on ultrasound scanning, and compact bundles of collagen fibrils with bimodal
      distribution of the diameters. The blisters appeared as an echo-free band in the
      subepidermal zone by ultrasound scanning. Electron microscopy revealed blisters
      in the upper papillary dermis, surrounded by degraded collagen fibrils.

PMID- 1980990
TI  - Effect of nootropic and psycho-stimulants on children with infantile brain
      damages.

PMID- 1980991
TI  - Histamine and abnormal automaticity in barium- and strophanthidin-treated sheep
      Purkinje fibers.
AB  - We used intracellular microelectrodes to study the effects of histamine on both
      normal and abnormal automaticity in sheep Purkinje fibers. Histamine, dimaprit
      and 4-methylhistamine caused a similar reduction of the action potential duration
      in driven Purkinje fibers. Histamine (10-6 M) induced spontaneous activity in p
      previously quiescent preparations more often than did equimolar concentrations of
      dimaprit and 4-methylhistamine. The effects of histamine on automaticity were
      enhanced in the presence of barium In fact histamine, at concentrations which
      were unable to induce automaticity in normal preparations, induced it in the
      presence of barium. In Purkinje fibers manifesting barium-induced automatic
      activity, histamine (10-7--10-6M) significantly increased the average number of
      spontaneous action potentials and shortened the time of their appearance. In the
      same range of concentrations, histamine dose-dependently increased the iological
      manifestation of calcium overload. Histamine (10-6--10-4M) increased the OAP
      amplitude of strophanthidin -treated Purkinje fibers, eventually inducing
      triggered extrabeats. All these previously described effects were selectively
      blocked by cimetidine (10-5 M). It is concluded that histamine may induce cardiac
      arrhythmias under conditions of calcium overload and that this effect may be due
      to induction or enhancement of oscillatory afterpotentials.

PMID- 1980992
TI  - The choice of controlled hypotension during repair of intracranial aneurysms:
      techniques and complications.
AB  - Induced hypotension is frequently used during cerebral aneurysm dissection and
      clipping to reduce the risk of rupture. The ideal hypotensive agent does not
      exist and many drugs are currently used for the purpose of inducing hypotension.
      When used correctly serious complications are rare. These complications are
      either related to (1) the physiological effects of hypotension on the vital
      organs, namely, the brain, the heart, the lungs, the liver and the kidneys, or
      (2) the pharmacology of the respective hypotensive agent used which currently
      include the direct vasodilators-sodium nitroprusside and nitroglycerin;
      inhalation agents--isoflurane, enflurane and halothane; ganglionic blocker-
      trimethaphan; alpha/beta blockers- labetalol, esmolol; calcium channel blockers;
      and the experimental compound adenosine. Familiarity with both the physiology and
      pharmacology of induced hypotension will reduce the risk of complications of this
      useful technique.

PMID- 1980993
TI  - [The beginnings, development and decline of a technique: controlled deep arterial
      hypotension].
AB  - Everything started with hypovolemic hypotension (bleeding). But that was the
      stone age. Later, postural and drug induced normovolemic methods were used. The
      golden age of deliberate hypotension spanned the period from 1948 to 1980,
      culminating in 1975. The benefit/risk ratio was first positive, then variable and
      turned out to be questionable with the advent of deep hypotension, a challenge to
      brain hemodynamics. Progress in hemostasis surgical practices defeated deliberate
      hypotension. Today it is only applied in exceptional cases.

PMID- 1980994
TI  - Atrial-specific granule number and plasma atrial natriuretic peptide in rats:
      effects of beta-adrenoceptor blockade and sodium intake.
AB  - An interrelationship between atrial natriuretic peptide (ANP) and the renin
      angiotensin system has been established. Both of these hormonal systems are
      modulated by sodium balance. The role of the beta-adrenoceptor in the regulation
      of release of ANP is not clear. We therefore undertook a study to examine changes
      in atrial-specific granule number and plasma ANP level following beta
      adrenoceptor blockade in rats on low and high sodium intakes. A low-sodium diet,
      as compared with a high-sodium diet, elevated right and left atrial-specific
      granule number (right atria 54.6 +/- 8.7 vs. 42.3 +/- 5.7; left atria 47.7 +/-
      7.7 vs. 30.6 +/- 3.4 granules/unit area) and plasma renin activity (28 +/- 3.7
      vs. 5.4 +/- 0.8 ng AI/ml/hr). Plasma ANP levels were lower in the low-sodium
      animals (98 +/- 34 vs. 345 +/- 38 pg/ml). When treated with the nonspecific beta
      adrenoceptor blocker propranolol, the elevated plasma renin activity and atrial
      specific granule number in rats on a low sodium intake were significantly less.
      Neither of these parameters changed in rats on a high sodium intake. Conversely,
      propranolol treatment resulted in lower plasma ANP levels in rats with high
      sodium intake. The already-suppressed plasma ANP level in rats on a low-sodium
      diet was unaltered with beta-adrenoceptor blockade. The results suggest that
      dietary sodium intake is an important determinant of the response of atrial
      specific granule number and plasma ANP levels following beta-adrenoceptor
      blockade with propranolol.

PMID- 1980995
TI  - Assignment of the polymorphic intestinal mucin gene (MUC2) to chromosome 11p15.
AB  - A cDNA coding for a mucin expressed in intestine has recently been cloned (Gum et
      al. 1989). We describe here the use of this cDNA to map the gene (MUC2) to human
      chromosome 11 using somatic cell hybrids, and to make the regional localization
      to 11p15 by in situ hybridization. Analysis of the CEPH (Centre d'Etude du
      Polymorphisme Humain) families revealed that MUC2 forms part of the tight linkage
      group on 11p15 which contains HRAS, INS, TH and HBBC.

PMID- 1980996
TI  - The human Y chromosome shows a low level of DNA polymorphism.
AB  - Six new Y-specific probes have been isolated and are reported. Along with another
      six already described they have been used in a systemic search for male specific
      RFLPs. An overall number of 46515 nucleotides have been screened with 12 enzymes
      and no polymorphic pattern observed. Our data reveal a greatly reduced level of
      polymorphism compared with other chromosomes.

PMID- 1980997
TI  - Changes of CD2 receptor density determined by electron microscopy on blood
      lymphocytes following radiation treatment for breast cancer.
AB  - Changes of relative CD2 receptor on lymphocytes were examined in 11 women
      following radiation treatment for breast cancer by electron microscopy using
      antibody-coated gold particles. Proportions of blood lymphocytes with a high
      density of CD2 receptors were reduced, whereas those with no or a low density of
      such receptors were increased after radiation treatment.

PMID- 1980998
TI  - Ras, C-myc and C-erbB-2 oncoprotein expression in non-AIDS Mediterranean Kaposi's
      sarcoma.
AB  - We have studied ras p21, c-myc p62 and c-erbB-2 oncogene expression in fourteen
      Greek patients with NON AIDS Mediterranean Kaposi's sarcoma using
      immunohistochemical analysis. Elevated expression of ras p21 expression was
      observed in all 14 cases studied (8 of which had intense levels of staining),
      whereas expression of c-myc and c-erbB-2 was less frequent, (6 out of 13 cases
      tested showed elevated c-myc expression and 6 out of 13 showed elevated c-erbB-2
      expression). This report indicates that aberrant ras p21 oncogene expression is a
      feature of Kaposi's sarcoma and may be important in the early stages of this
      disease.

PMID- 1980999
TI  - Selective reduction of quisqualate (AMPA) receptors in Alzheimer cerebellum.
AB  - Multiple sites involved in glutamatergic neurotransmission were examined in the
      cerebellar cortex of 6 patients with Alzheimer's disease and 6 age-matched
      control patients by using quantitative ligand-binding autoradiography.
      Quisqualate (AMPA) receptor binding was markedly reduced in the molecular layer
      of the cerebellum from patients with Alzheimer's disease (167 +/- 13 pmoles/gm)
      compared with control patients (280 +/- 13 pmoles/gm). In adjacent sections from
      the same patients and controls, there was preservation of kainate and N-methyl-D
      aspartate receptor binding in the cerebellum from patients with Alzheimer's
      disease compared with control patients. Neuropathological examination of the
      cerebellar cortex revealed the presence of plaques and preservation of Purkinje
      cells in the patients with Alzheimer's disease.

PMID- 1981000
TI  - Influence of antacid and ranitidine on the pharmacokinetics of oral cefetamet
      pivoxil.
AB  - The purpose of this investigation was to assess the influence that treatment with
      antacid and ranitidine had on the pharmacokinetics of oral cefetamet pivoxil in
      18 healthy male volunteers. Each subject received, in an open-labeled,
      randomized, three-way crossover design, a single oral dose of 1,000 mg (two
      tablets) of cefetamet pivoxil 10 min after a standard breakfast during each of
      the following treatments: treatment A, control period; treatment B, antacid (80
      ml of suspension; Maalox 70) administered on the evening before cefetamet pivoxil
      dosing (-12.5 h) and again 2 h before and 2 h after a standard breakfast;
      treatment C, ranitidine (150 mg) administered twice a day for 4 days and again 1
      h and 10 min prior to cefetamet pivoxil dosing. Plasma and urine samples were
      collected over a 24-h period following cefetamet pivoxil administration.
      Cefetamet was analyzed by high-performance liquid chromatography. Oral
      bioavailability parameters (area under the concentration-time curve from 0 to 12
      h, area under the concentration-time curve from 0 h to infinity, time to maximum
      concentration of drug in plasma, and maximum concentration of drug in plasma)
      were obtained by noncompartmental techniques. The results showed that none of
      these bioavailability parameters was significantly (P greater than 0.05) affected
      by antacid or rantidine coadministration. A compartmental analysis showed no
      significant differences. In addition, the terminal elimination half-life and the
      fraction of cefetamet excreted unchanged in the urine was also not significantly
      (P greater than 0.05) affected by antacid or ranitidine exposure. Relatively wide
      intrasubject variability was observed for time to maximum concentration of drug
      in plasma and terminal elimination half-life in several of the 18 subjects
      studied. Although these irregularities did not appear to be strongly associated
      with a particular treatment, they increased in subjects in both the antacid and
      H2-receptor antagonist treatment groups compared with those in subjects in the
      control treatment group. We conclude that antacid and ranitidine treatment likely
      does not alter the bioavailability of oral cefetamet pivoxil.

PMID- 1981001
TI  - Restriction fragment length polymorphism of the Vibrio anguillarum serovar O1
      virulence plasmid.
AB  - Seventy-eight strains of Vibrio anguillarum serovar O1, all harboring one 65- to
      70-kilobase plasmid, were typed according to restriction fragment length
      polymorphism of the plasmid. Six types, three of which comprised 96% of the
      strains examined, were produced with the restriction endonuclease BamHI. The
      fragment length polymorphism type did not correlate to any of 12 different
      phenotypic properties tested.

PMID- 1981002
TI  - [ Biological criteria for prediction of the clinical course leading to AIDS].

PMID- 1981003
TI  - Effect of human seminal plasma on the lytic activity of natural killer cells and
      presumptive identification of participant macromolecules.
AB  - Using the lytic activity of natural killer (NK) cells as an in vitro parameter,
      the immunoregulatory properties of human seminal plasma (SePl) and participant
      macromolecules have been investigated. Significant (P less than 0.05) suppression
      of NK cell activity by SePl and chromatographically separable fractions was
      demonstrated in association with high and low molecular weight (Mr)
      macromolecules. SePl suppression was retained after heating to 56 degrees C for
      30 min, and appeared to function at the level of the effector, rather than target
      cell. Physicochemical characterization of high and low Mr fractions provided
      presumptive identification of the participation of transglutaminase and
      prostaglandins as the principal molecules contributory to SePl immunosuppression.

PMID- 1981004
TI  - Locomotor stepping initiated by glutamate injections into the hypothalamus of the
      anesthetized rat.
AB  - Glutamate (50 mM, 50 nl) injected into the tuberal and posterior hypothalamus was
      tested for capacity to elicit locomotor stepping. Rats (n = 23) were anesthetized
      with Nembutal and suspended by a sling in a stereotaxic apparatus such that
      locomotor stepping rotated a wheel. In 61 of 275 sites tested, stepping was
      initiated by glutamate injections within 60 s. Positive sites were widespread and
      contained in the lateral hypothalamus, the perifornical area, the dorsomedial
      nucleus, and the zona incerta. The perifornical and lateral hypothalamic sites
      were most likely to have locomotor responses and the shortest latencies. These
      findings indicate that selective activation of hypothalamic neurons as opposed to
      fibers of passage can initiate locomotion.

PMID- 1981005
TI  - IgE-mediated drug fever due to histamine H2-receptor blockers.
AB  - Drug-induced fever due to histamine H2-receptor blockers was experienced by a 55
      year-old man. The patient became febrile 5 days after receiving cimetidine, and
      continued to be febrile until the drug was stopped. His maximum body temperature
      was above 40 degrees C. Challenge tests with cimetidine and ranitidine showed
      that the fever was caused by the H2-blocker. The patient's serum IgE
      concentration increased markedly to 2590 IU/ml 10 days after admission, and skin
      tests for cimetidine and ranitidine were positive. Lymphocyte stimulation tests
      were positive for both drugs (stimulation indices: 193% for cimetidine and 325%
      for ranitidine). Cimetidine-induced fever has generally been thought to be due to
      a direct effect on the thermoregulatory centre in the hypothalamus, on the basis
      of experimental studies of the injection of cimetidine to the cerebral
      ventricles. However, clinical evidence has not excluded an allergic involvement
      in this type of drug-induced fever. This patient's fever was proven to be due to
      administration of the H2-blocker, and the mechanism of action was IgE-mediated.

PMID- 1981006
TI  - Novel structure and genetics of prions causing neurodegeneration in humans and
      animals.

PMID- 1981007
TI  - Establishment and characterization of a human CD4 positive cell bank for HIV
      related studies.
AB  - The human CD4 positive cell lines JM, CCRF, CEM, U937, HL60 and THP-1 have been
      cleared of mycoplasma contamination and defined by DNA fingerprinting and cell
      surface phenotype marker analysis. These cells have been banked and are now
      available as a source of standardized cell lines for HIV related research.

PMID- 1981008
TI  - Methylprednisolone in the treatment of Wegener's granulomatosis, polyarteritis
      nodosa and Churg-Strauss angiitis.

PMID- 1981009
TI  - Antitumor effects of analogs of LH-RH and somatostatin: experimental and clinical
      studies.
AB  - Many clinical approaches for the treatment of hormone-sensitive tumors are being
      developed based on analogs of LH-RH and somatostatin. Inhibition of the pituitary
      gonadal axis forms the basis for oncological applications of LH-RH agonists like
      [D-Trp6]-LH-RH and new LH-RH antagonists free of edematogenic effects such as [Ac
      D-Nal(2)1-D-Phe(4Cl)2-D-Pal(3)3,D-Cit6,D-Ala10]-LH -RH (SB-75). Agonists and
      antagonists of LH-RH have been used in patients with prostate cancer and might be
      also beneficial for the treatment of breast cancer and ovarian, endometrial and
      pancreatic carcinomas. Some of the effects of LH-RH analogs can be due to direct
      action since LH-RH receptors have been found in these cancers. The use of
      sustained delivery systems based on microcapsules of PLG, makes the treatment
      more efficacious. Octapeptide analogs of somatostatin such as D-Phe-Cys-Tyr-D-Trp
      Lys-Val-Cys-Trp-NH2 (RC-160) and related analogs were designed specifically for
      antitumor activity. These somatostatin analogs, by virtue of having a wide
      spectrum of activities appear to inhibit various tumors through multiple
      mechanisms. Direct antiproliferative actions of somatostatin analogs appear to be
      mediated by specific receptors located on tumor cells. High affinity binding
      sites for RC-160 and related analogs have been found in human pancreatic,
      prostate, breast and ovarian cancers and brain tumors such as meningiomas. In
      vivo administration of analog RC-160 inhibits the growth of Dunning R-3327
      prostate cancers in rats, MXT mammary tumors in mice and BOP-induced ductal
      pancreatic cancers in hamsters. Combination of microcapsules of RC-160 with [D
      Trp6]-LH-RH results in synergistic potentiation of the inhibition of these
      cancers. Somatostatin analog RC-160 and LH-RH antagonist SB-75 are the object of
      further experimental studies and clinical trials aimed at the exploration of
      their inhibitory effects on the processes of malignant growth.

PMID- 1981010
TI  - Somatostatin receptors in malignant tissues.
AB  - High affinity somatostatin receptors (SS-R) have been identified in membrane
      homogenates or tissue sections from several hundred human tumors. SS-R were found
      in most tumors originating from SS target tissues, i.e. GH- and TSH-producing
      pituitary tumors, endocrine gastroenteropancreatic (GEP) tumors (including
      metastases) and brain tumors, including gliomas and neuroblastomas. SS-R were
      also expressed in several tumors originating from various other tissues, i.e.
      breast and small cell lung carcinomas, some colorectal cancers, and medullary
      thyroid carcinomas. In general, most of the SS-R+ tumors are well-differentiated
      and/or have neuroendocrine features. They often have low or absent epidermal
      growth factor receptor (EGF-R) expression. In some tumors (i.e. breast tumors) SS
      R are not homogeneously distributed, making SS-R autoradiography a particularly
      useful tool for assessing SS-R status. SS-R are functional in pituitary and GEP
      tumors where they mediate hormone secretion inhibition. In these and in the other
      SS-R+ tumors, SS-R may also mediate antiproliferative effects of SS, as evidenced
      in animals where growth of SS-R+ tumor xenografts is inhibited by SS analogs. For
      diagnosis, SS-R+ tumors and metastases can be localized in vivo by scanning
      techniques after 123I-labelled SS analog injection.

PMID- 1981011
TI  - Somatostatin receptor imaging in vivo localization of tumors with a radiolabeled
      somatostatin analog.
AB  - This paper presents the results of the visualization of somatostatin (SS)
      receptor positive tumors in man after the i.v. administration of the SS analog
      Tyr3-octreotide coupled to 123I. It is an easy, quick and harmless procedure
      which allows imaging of primary and (often unexpected) secondary deposits and/or
      multiple localizations of the majority of endocrine pancreatic tumors, metastatic
      carcinoids and pituitary tumors, as well as of a multitude of tumors with
      neuroendocrine characteristics and well-differentiated brain tumors and
      meningiomas. In the case of hormone-secreting tumors a positive scan in most
      instances also predicts the subsequent successful therapy with octreotide.

PMID- 1981012
TI  - Somatostatin analogues in the treatment of breast and prostate cancer.
AB  - Newly developed somatostatin analogues may be useful agents in the treatment of
      breast and prostate cancer. Potential mechanisms of antitumor action include
      suppression of circulating levels of trophic hormones and growth factors as well
      as direct effects at the tumor level, potentially involving autocrine/paracrine
      mechanisms. Pilot clinical trials conducted in heavily pretreated women with
      advanced breast cancer indicate that SMS 201-995 (Sandostatin R) has minimal
      toxicity and moderately suppresses stimulated growth hormone secretion and basal
      somatomedin-C level. Somatostatin analogues have also been found to retard the
      growth of experimental prostate cancer, particularly when used in combination
      with LHRH analogues. The therapeutic efficacy of these compounds used alone or in
      combination with other agents in the treatment of breast and prostate cancer
      remains to be established in larger clinical trials involving less heavily
      pretreated patients.

PMID- 1981013
TI  - Growth factor-receptor pathway interfering treatment by somatostatin analogs and
      suramin: preclinical and clinical studies.
AB  - Interference in growth factor mediated pathways is a new strategy in the
      treatment of cancer. Somatostatin analogs can inhibit hormone and growth factor
      secretion, while suramin can block the binding of several growth factors to their
      receptors. In addition, somatostatin analogs can cause direct growth inhibitory
      effects after binding to tumoral somatostatin receptors. We tested the efficacy
      and endocrine effects of chronic treatment with three somatostatin analogs
      (Sandostatin, R RC-160 and CGP 15-425) or suramin in several tumor models and in
      patients with various types of cancer. Treatment with somatostatin analogs caused
      growth inhibition of breast cancer cells (MCF-7) in vitro, and of rat
      transplantable pancreatic (50-70% inhibition) and prostatic Dunning tumors (12%
      inhibition). No tumor growth inhibition was observed with respect to DMBA-induced
      rat mammary tumors, a transplantable colon tumor and a rhabdomyosarcoma in rats.
      In 34 patients with metastatic pancreatic or gastrointestinal adenocarcinomas
      chronic Sandostatin treatment caused stable disease in 27% of the patients, but
      no objective remissions. Somatostatin receptors were found in the responding MCF
      7 mammary tumor cells, rat pancreatic tumors and in 20-45% of human breast cancer
      specimens [J. Steroid Biochem. Molec. Biol. 37 (1990) 1073-1077], but not in rat
      DMBA-mammary tumors or in 10 human pancreatic adenocarcinomas. Suramin caused
      significant dose-dependent growth inhibition of human breast cancer cells in
      vitro and of rat pancreatic tumors in vivo in the presence of plasma levels up to
      150 micrograms/ml. In a preliminary clinical study concerning 11 patients with
      various tumor types we observed significant hematological, biochemical, endocrine
      and clinical side effects, but no objective remissions in spite of relevant peak
      plasma suramin concentrations of 270-330 micrograms/ml. IN CONCLUSION:
      somatostatin analogs and suramin can cause growth inhibition of various
      experimental tumors in vitro and in vivo, but the clinical value has to be
      established for several types of cancer, especially with respect to suramin and
      suramin-like compounds.

PMID- 1981015
TI  - Proceedings of the second international EORTC symposium on hormonal manipulation
      of cancer: peptides, growth factors and new (anti-)steroidal agents. Rotterdam,
      The Netherlands, 9-11 April 1990.

PMID- 1981014
TI  - In vivo manipulation of human breast cancer growth by estrogens and growth
      hormone: kinetic and clinical results.
AB  - Since 1983, a series of experimental and clinical studies have been carried out
      on the possibility of enhancing the chemotherapy effectiveness in breast cancer
      by expanding the fraction of cycling cells. Theoretically estrogens should
      recruit breast cancer cells and this fact should result in a higher killing
      efficiency of antiproliferative drugs. Actually it has been clearly shown, by
      means of the thymidine labeling index and primer-dependent alpha-DNA polymerase
      assay, that low doses of diethylstilbesterol are able to increase the tumor
      proliferative activity of human breast cancer in vivo (estrogenic recruitment).
      Three randomized trials have been carried out (one in locally advanced and two in
      metastatic breast cancer) comparing conventional polychemotherapy vs chemotherapy
      with estrogenic recruitment. Only limited advantages have been observed in these
      trials. Searching for new modalities of kinetic manipulation of tumors,
      recombinant human growth hormone has been employed in a pilot study: the
      preliminary results indicate that it largely enhances tumor proliferative
      activity, suggesting the possibility of employing a growth factor system to
      increase chemosensitivity.

PMID- 1981016
TI  - Genetic changes in somatostatin receptor positive breast tumors.
AB  - Forty-nine primary breast tumors were analyzed for the expression of the
      somatostatin receptor (SSR) and genetic changes in the RB tumor suppressor gene.
      Twenty-four tumor samples were shown to contain receptors for somatostatin and in
      eight of these SSR-positive tumors we observed a mutation in the RB gene.
      However, since also in the group of SSR-negative tumors in eight of the 25 cases
      an alteration of the RB gene was observed, loss of this tumor suppressor gene is
      not specific for the SSR-positive subgroup of breast tumors. A similar, equal
      distribution between SSR-positive and SSR-negative breast tumors was observed for
      the six tumor samples which showed amplification of the neu proto-oncogene.

PMID- 1981017
TI  - A double-blind comparison of bisoprolol and captopril for treatment of essential
      hypertension in the elderly.
AB  - The aim of the study was to compare the antihypertensive efficacy and safety of a
      new beta blocker with high beta 1 selectivity, bisoprolol, with captopril in 28
      elderly patients, aged over 65 years, with mild-to-moderate essential
      hypertension (WHO classes I and II). After a placebo run-in period of 4 weeks,
      the patients were randomly allocated to receive bisoprolol (5 mg od) or captopril
      (25 mg bid) (double-dummy technique) for 6 weeks, according to a crossover double
      blind design, with a 4-week washout period between the two active treatments. The
      doses were doubled after 2 weeks if the supine blood pressure was greater than
      160/95 mmHg. In basal conditions and after 2, 4, and 6 weeks of each treatment,
      the blood pressure and heart rate were assessed both in the supine and erect
      positions. At the same time, the side effects and quality of life were
      investigated by a checklist and a self-assessment questionnaire. Standard
      laboratory tests and a resting ECG tracing were performed before and after each
      active treatment. The data from 24 patients (4 dropouts) showed a significant
      antihypertensive effect of both treatments (p less than 0.01) with a reduction of
      diastolic blood pressure to values less than or equal to 95 mmHg in 75% (18/24)
      of the patients treated with bisoprolol and in 83.3% (20/24) of those treated
      with captopril, without significant differences between the two drugs. Bisoprolol
      also produces a marked but symptom-free reduction of heart rate compared with
      captopril (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1981018
TI  - Felodipine prevents the poststenotic myocardial ischemia induced by alpha 2
      adrenergic coronary constriction.
AB  - Alpha 2-adrenoceptor-mediated coronary constriction contributes to the
      precipitation of myocardial ischemia during sympathetic activation. Felodipine is
      a novel dihydropyridine calcium-channel antagonist with vascular selectivity. In
      this study, the effect of felodipine on alpha 2-adrenoceptor-mediated
      poststenotic coronary constriction was investigated. In ten open-chest dogs, the
      selective alpha 2-adrenoceptor agonist BHT 933 (200 micrograms IC) was infused
      before and after production of a severe stenosis on the left circumflex coronary
      artery. BHT 933 increased calculated resistance of the intact left circumflex
      coronary artery from 1.16 +/- 0.30 (SD) to 2.00 +/- 0.70 mmHg*min*100 g/ml (p
      less than 0.05) without changing posterior systolic wall thickening
      (sonomicrometry) (14.2 +/- 2.8% vs. 14.1 +/- 2.7%). In the presence of a severe
      stenosis, BHT 933 increased poststenotic coronary resistance from 1.59 +/- 0.54
      to 2.88 +/- 1.16 mmHg*min*100 g/ml (p less than 0.05) and decreased posterior
      systolic wall thickening from 11.9 +/- 2.7% to 8.2 +/- 3.1% (p less than 0.05).
      In contrast, after intravenous pretreatment with felodipine (4 micrograms/kg),
      intracoronary infusion of BHT 933 did not change coronary resistance (1.69 +/-
      0.61 vs. 1.61 +/- 0.64 mmHg*min*100 g/ml) and posterior systolic wall thickening
      (12.1 +/- 3.0% vs. 12.6 +/- 2.9%). In conclusion, felodipine prevents alpha 2
      adrenoceptor-mediated coronary constriction and ischemic regional myocardial
      dysfunction distal to a severe coronary stenosis.

PMID- 1981019
TI  - Interaction of tertatolol with rifampicin and ranitidine pharmacokinetics and
      antihypertensive activity.
AB  - The interaction of the new beta-receptor antagonist tertatolol with rifampicin
      and ranitidine was investigated in ten patients with arterial hypertension (WHO
      stages I-II). They were treated orally with a single dose of tertatolol 5 mg
      alone and, after randomized allocation, with ranitidine 150 mg twice daily or
      rifampicin 600 mg once daily for 1 week each (tertatolol 5 mg was concurrently
      administered on the seventh day of the treatment phases). Following each
      therapeutic phase, circadian blood pressure values as well as kinetic parameters
      were obtained. On treatment with tertatolol alone, maximum plasma concentrations
      were 123.7 +/- 32.4 ng/ml (mean +/- SD) and were reached after 1.95 +/- 1.77
      hours. The tertatolol elimination half-life was 9.0 +/- 7.1 hours.
      Coadministration of ranitidine did not significantly alter the kinetic parameters
      and antihypertensive effect of tertatolol. Rifampicin, however, decreased the
      maximum plasma levels of tertatolol to 80.6 +/- 18.5 ng/ml and markedly shortened
      the elimination half-life to 3.4 +/- 2.6 hours (p less than 0.01 compared with
      tertatolol alone). Urinary excretion of parent tertatolol and unchanged 4-hydroxy
      tertatolol was decreased under rifampicin, and a tendency to a reduction in the
      effect of tertatolol on circadian blood pressure values was observed. Twenty-four
      hours after administration, the heart rate in those patients on tertatolol alone
      (68 +/- 6 beats/min) was lower than in those on tertatolol plus rifampicin (74 +/
      7 beats/min). In conclusion, a pronounced pharmacokinetic interaction, with a
      limited consequence in terms of pharmacodynamic effects, was found in the present
      study when tertatolol was administered with rifampicin, but not with ranitidine.

PMID- 1981020
TI  - Effects of nifedipine versus hydralazine on sympathetic activity and cardiac
      function in patients with hypertension persisting on diuretic plus beta-blocker
      therapy.
AB  - In patients with hypertension persisting on combined diuretic and beta-blocker
      therapy, the effects of an additional 9-week therapy with a calcium antagonist
      (nifedipine) versus a classical arterial vasodilator (hydralazine) were compared
      for changes in blood pressure (BP), plasma catecholamines (n = 15), and left
      ventricular (LV) systolic and diastolic function (n = 6). Both drugs lowered BP,
      but nifedipine was significantly more effective in lowering systolic BP.
      Hydralazine increased both supine and standing plasma norepinephrine, nifedipine
      increased them only in the standing position and to a lesser extent. Patients on
      beta1-selective (n = 5) versus nonselective (n = 10) blockade showed similar
      responses. Left ventricular systolic function was not affected by hydralazine,
      whereas nifedipine increased the rate of ejection. In contrast, LV diastolic
      function was not affected by nifedipine, whereas hydralazine improved the peak
      filling rate. We conclude that arterial vasodilation by a calcium antagonist
      causes less sympathetic activation than caused by a classical arterial
      vasodilator. However, during short-term therapy in patients already on a diuretic
      and a beta blocker, nifedipine appears not to improve decreased LV diastolic
      function.

PMID- 1981022
TI  - Serotonin antagonism reduces the adverse symptoms of beta blockade.
AB  - Beta-adrenoceptor antagonists (beta blockers) are a well-established first-line
      treatment for hypertension, but they have been associated with unwanted symptoms
      including cold extremities, lethargy, and nightmares. Ketanserin is a serotonin
      S2-receptor antagonist that has previously been shown to reduce blood pressure in
      hypertensive patients by reducing systemic vascular resistance. Hypertensive
      patients whose sitting diastolic blood pressure was greater than or equal to 95
      mmHg, despite at least 4 weeks therapy with an optimal dose of beta blocker, were
      selected for the study. The beta-blocker dose remained constant throughout the
      study, but patients were randomly allocated to receive ketanserin 20 mg twice
      daily, ketanserin 40 mg twice daily, or bendrofluazide 5 mg each morning plus
      placebo at night in addition to the beta-blocker therapy. One hundred and forty
      two patients completed the symptom questionnaire at randomization and after 12
      weeks treatment. The treatment groups were well matched for age, sex, weight, and
      blood pressure. Blood pressure was reduced significantly by all treatments, and
      there were no between-group differences. Bendrofluazide adversely affected
      alertness (p less than 0.05) and concentration (p less than 0.01) whereas
      ketanserin had no significant effect and the ketanserin 20 mg twice daily group
      had better concentration than the bendrofluazide group (p less than 0.05).
      Ketanserin treatment reduced the incidence of nightmares (p less than 0.05 for 20
      mg twice daily and 40 mg twice daily) and was an improvement over bendrofluazide
      treatment in this respect (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1981021
TI  - Electrophysiologic effects of intravenous xamoterol in patients with sinus node
      dysfunction.
AB  - The electrophysiologic effects of xamoterol were studied in ten patients with
      electrophysiologic evidence of sinus node dysfunction. A significant shortening
      of mean sinus cycle length, maximal corrected sinus-node recovery time, and the
      mean of the three longest corrected sinus-node recovery times was observed after
      intravenous administration of 0.1 mg/kg of xamoterol. The atrioventricular (AV)
      conduction time and the effective and functional refractory periods of the AV
      node were shortened as the effective refractory period of the atrium. These
      effects suggest that xamoterol could be tried safely for the treatment of
      patients with moderate symptoms due to sinus-node disease.

PMID- 1981023
TI  - Effects of ketanserin tartrate on 3-hydroxy, 3-methylglutaryl coenzyme A
      reductase activity in cultured human skin fibroblasts.
AB  - Ketanserin tartrate (ketanserin) is a new antihypertensive drug that is a
      selective 5HT2 serotonergic receptor antagonist and at high concentrations
      antagonizes the alpha 1-adrenergic receptor. Several reports have indicated that
      ketanserin clinically decreases plasma low density lipoprotein (LDL) cholesterol.
      In order to clarify the mechanisms of this LDL cholesterol reduction by
      ketanserin, we investigated the effects of ketanserin on 3-hydroxy, 3
      methylglutaryl coenzyme A(HMG CoA) reductase activity to cultured human skin
      fibroblasts. We also studied the effects of ritanserin (a 5HT2 serotonergic
      receptor antagonist) and prazosin HCl (an alpha 1-adrenergic receptor antagonist)
      on HMG CoA reductase activity in cultured human skin fibroblasts. Human skin
      fibroblasts were cultured in Dulbecco's modified Eagle's (DME) medium containing
      10% fetal calf serum. Before the cells reached confluence, the medium was changed
      to DME containing 10% lipoprotein-deficient serum. After incubation for 48-72
      hours, the drugs under investigation were added to the medium. The cells were
      incubated for 14 hours and harvested after washing with phosphate buffered
      saline. In our study, ketanserin decreased HMG CoA reductase activity in a dose
      dependent manner up to 300 ng/ml (550 nM). Prazosin also decreased HMG CoA
      reductase activity in a dose-dependent manner up to 40 ng/ml (95 nM); ritanserin
      decreased HMG CoA reductase activity at concentrations of 100 nM and 200 nM.
      These findings suggest that the combination of alpha 1-adrenergic receptor and
      5HT2 serotonergic receptor antagonist effects of ketanserin inhibits HMG CoA
      reductase activity and that this suppression is probably one of the mechanisms
      for the plasma LDL cholesterol reduction resulting from ketanserin treatment.

PMID- 1981024
TI  - The Glu 2- ... Arg 10+ side-chain interaction in the C-peptide helix of
      ribonuclease A.
AB  - Previous studies have identified Lys 1, Glu 2, and His 12 as the charged residues
      responsible for the pH-dependent stability of the helix formed by the isolated C
      peptide (residues 1-13 of ribonuclease A). Here we examine whether the helix
      stabilizing behavior of Glu 2- results from a Glu 2- ... Arg 10+ interaction,
      which is known to be present in the crystal structure of ribonuclease A. The
      general approach is to measure the helix content of C-peptide analogs as a
      function of three variables: pH (titration of ionizing groups), amino acid
      identity (substitution test), and NaCl concentration (ion screening test). In
      order to interpret the results of residue replacement, several factors in
      addition to the putative Glu 2- ... Arg 10+ interaction have been studied:
      intrinsic helix-forming tendencies of amino acids; interactions of charged
      residues with the alpha-helix macrodipole; and helix-lengthening effects. The
      results provide strong evidence that the Glu 2- ... Arg 10+ interaction is linked
      to helix formation and contributes to the stability of the isolated C-peptide
      helix. NMR evidence supports these conclusions and suggests that this interaction
      also acts as the N-terminal helix stop signal. The implications of this work for
      protein folding and stability are discussed.

PMID- 1981025
TI  - Characterization of immobilized hepatocytes as liver support.
AB  - Hepatocytes isolated from rat liver were immobilized within Ca-alginate.
      Immobilized hepatocytes could remove ammonia and other toxic substances causing
      hepatic coma, such as indole, phenol, bilirubin, and short chain fatty acids.
      Although free hepatocytes lost those activities within 2 days, immobilized
      hepatocytes maintained those activities for more than 7 days. Immobilized
      hepatocytes induced tyrosine aminotransferase (TAT) in the presence of
      dexamethasone and dibutyryl-cAMP and retained the ability to induce TAT for more
      than 7 days. Biologically active form of coagulation factor II, prothrombin could
      be synthesized and secreted into medium by immobilized hepatocytes. Moreover,
      immobilized hepatocytes produced glucose from lactate, alanine, fructose, and
      galactose. Like adult rat liver, growth-related function and liver-specific
      function in immobilized hepatocytes were reciprocally controlled by cell density.
      There are both alpha-, and beta-adrenergic receptors in membrane of liver cells,
      and the adrenergic action of epinephrine is alpha-predominant in adult rat liver.
      Monolayer-cultured hepatocytes can not maintain alpha-adrenergic response.
      However, immobilized hepatocytes maintained alpha-adrenergic response as shown in
      vivo. Those characteristics of immobilized and three-dimensionally cultured
      hepatocytes are regarded almost the same as liver cells in vivo. Furthermore,
      therapeutic effect of immobilized hepatocytes on the hepatic failure were
      confirmed in the experiment using hepatocytes damaged with D-galactosamine.
      Therefore, it is suggested that immobilized hepatocytes could be applied to a
      hybrid artificial liver support.

PMID- 1981026
TI  - [Acute pulmonary edema in a 2-year-old child during peridural anesthesia].
AB  - A case of post obstructive pulmonary oedema in a two year old asthmatic child
      under epidural anaesthesia is described in this case report. The possible causes
      and mechanisms of this complication and its management are discussed. This
      discussion underlines that a minor degree of upper airway obstruction might have
      been capable of producing pulmonary oedema because of the altered lung function
      in this child.

PMID- 1981027
TI  - Na(+)-dependent Ca2+ influx in bovine adrenal chromaffin cells.
AB  - Bovine adrenal chromaffin cells were loaded with Na+ via either acetylcholine
      receptor-associated ion channels or voltage-sensitive Na+ channels. There were
      increases in [Ca2+]i, 45Ca2+ uptake and catecholamine secretion in both types of
      Na(+)-loaded cells relative to control cells in which Na+ loading had been
      prevented by hexamethonium and tetrodotoxin, respectively. These results show the
      presence of Na(+)-dependent Ca2+ influx activity in chromaffin cells which is
      probably mediated by the reverse mode of a Na+/Ca2+ exchanger.

PMID- 1981028
TI  - Comparative pharmacokinetics of sulpiride and N-[(1-butyl-2-pyrrolidinyl)methyl]
      2-methyl-5-sulfamoyl-2,3- dihydrobenzofuran-7-carboxamide hydrochloride, a new
      lipophilic substituted benzamide in rats.
AB  - The pharmacokinetics of a new lipophilic substituted benzamide N-[(1-butyl-2
      pyrrolidinyl)methyl]-2-methyl-5-sulfamoyl-2,3- dihydrobenzofuran-7-carboxamide
      hydrochloride (1) and sulpiride in both plasma and brain were investigated in
      rats. The octanol-water partition coefficients of the base of 1(2) and sulpiride
      were 6.3 and 0.2, respectively. The eliminations of 2 from plasma and brain were
      similar to those of sulpiride. The systemic bioavailabilities of 1 and sulpiride
      after oral administration of 200 mg/kg were 60.9 +/- 10.9 and 18.2 +/- 6.4%,
      respectively. The brain concentrations of 2 were about 2-3 times higher than
      those of sulpiride until 4 h after oral administration of 100 mg/kg. The
      brain/plasma ratios of 2 were about 2 times higher than those of sulpiride. These
      results indicate that the penetration of 2 through the gastrointestinal membrane
      and/or the blood-brain barrier are higher than those of sulpiride.

PMID- 1981029
TI  - Prenatal diagnosis of the neurofibromatoses.
AB  - This article reviews the application of genetic linkage analysis to molecular
      prenatal diagnosis using the neurofibromatoses as an example. The clinical
      manifestations and diagnostic criteria for these diseases are reviewed first,
      followed by a brief description of the principles underlying genetic linkage
      analysis, the detection of DNA polymorphisms and their application to the cloning
      of the NF1 gene. The last two sections review the molecular diagnosis and some of
      the problems in prenatal genetic counseling for NF1.

PMID- 1981030
TI  - Comparisons of hemodynamics throughout the life span of the Bio 14.6
      cardiomyopathic with the F1B normal hamster.
AB  - 1. Comparisons of left intraventricular end diastolic and systolic pressures,
      cardiac output, dP/dt, stroke volume and heart rate were made between the Bio
      14.6 cardiomyopathic and F1B normal hamster at 45, 80, 150 and 240 days of age.
      2. Comparisons of the ventricular calcium and taurine contents were made between
      the two strains of hamsters at similar ages. 3. Interstrain comparisons of the
      240 day Bio 14.6 with age matched F1B hamsters and intrastrain comparisons with
      45 day Bio 14.6 hamsters showed a decreased stroke volume, cardiac output and
      dP/dt with an increased left intraventricular end diastolic pressure, ventricular
      weight, ventricular weight/body weight ratio, heart calcium and taurine. 4.
      Despite the decreased left ventricular systolic pressure and cardiac output in
      the 80 day and older groups of Bio 14.6 hamsters, no compensatory increase in
      heart rate was observed.

PMID- 1981031
TI  - Seasonal change in metabolic rate of Drosophila simulans.
AB  - 1. Second-generation descendents of wild-caught female Drosophila simulans
      Sturtevant collected at different seasons from Gainesville, Florida, USA, were
      reared under a constant temperature and food level but with seasonally variable
      photoperiods. 2. Body weight and metabolic rate, after adjustment to a common
      body weight, were higher in descendents of flies collected in fall and winter. 3.
      Temperature sensitivity (Q10) of metabolic rate was also related to season:
      higher Q10 values were associated with seasons of increasing temperatures and
      lower Q10 values were associated with seasons of decreasing temperatures. 4.
      These metabolic characteristics may be adaptive in enhancing activity at lower
      temperatures and conserving energy at higher temperatures.

PMID- 1981032
TI  - Changes in mammary blood flow during the lactation period in goats measured by
      the ultrasound Doppler principle.
AB  - 1. Mammary blood flow was measured during the lactation period in two low- and
      two high-yielding dairy goats (peak milk yields approx. 1.5 and 3.6 kg/day
      respectively), using the ultrasound Doppler principle for determination of blood
      velocity in both milk veins (subcutaneous abdominal veins) of the animals, and
      ultrasound scanning for measurement of cross-sectional area of the veins. 2. Milk
      vein cross-sectional area ranged from 0.11 to 0.38 cm2 in the four goats, with a
      close to significant (P = 0.06) difference between the veins in the two sides of
      the animals. Cross-sectional area remained constant during the lactation period.
      Changes in mammary blood flow was therefore caused by changes in blood velocity.
      3. Milk vein blood velocities ranged from 4.4 to 34.7 cm/sec independently of the
      time of the day, and were of the same magnitude in the two sides of the animals.
      Except in one goat (P = 0.1), blood velocity decreased significantly (P less than
      0.01) with progressing lactation, during which period also milk yield was
      declining. 4. In the two low-yielding goats, a positive linear relationship (R2 =
      0.20) was found between milk yield and milk vein blood velocity, whereas a
      diminishing exponential relationship (R2 = 0.97) was found in the two high
      yielding goats. At a given milk vein blood velocity, high-yielding goats obtained
      a higher milk yield and also responded to changes in blood velocity (up to
      approx. 15 cm/sec) with greater increases in milk yield than low-yielding
      goats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1981033
TI  - Aldosterone increases gustatory neural response to NaCl in frog.
AB  - 1. The effect of aldosterone on frog gustatory response was investigated by
      recording integrated responses of the whole glossopharyngeal nerve elicited by
      taste stimuli. 2. After aldosterone (1 microM) was perfused to the basolateral
      side of taste cells through the lingual artery, the gustatory neural response for
      a NaCl stimulus was greatly enhanced, but the gustatory responses for CaCl2,
      hydrochloric acid, quinine hydrochloride and galactose were not affected. 3. At 3
      and 6 hr after the onset of aldosterone perfusion, the magnitudes of the
      responses for NaCl increased to 2.0 and 3.6 times the control, respectively. 4.
      These results suggest that aldosterone may regulate the gustatory responses for
      monovalent salts alone.

PMID- 1981034
TI  - Spontaneous hypoxaemia and right ventricular hypertrophy in fast growing broiler
      chickens reared at sea level.
AB  - 1. At 6 weeks of age, the time of most rapid body growth, fast growing broiler
      chickens showed more right ventricular hypertrophy than slower growing chickens.
      2. The degree of right ventricular hypertrophy was directly related to blood
      haematocrit and indirectly related to arterial oxygen saturation (estimated in
      the chickens using an ear oximeter designed for man). 3. When oxygen saturation
      was estimated sequentially from 6 to 17 weeks of age, mean oxygenation improved
      with age, partly due to the death of the chickens with the worst saturations, but
      also because of an improvement in oxygenation of the survivors.

PMID- 1981035
TI  - Large variations in skeletal muscle carnitine level fail to modify energy
      metabolism in exercising rats.
AB  - 1. The importance of carnitine status in energy metabolism during exercise was
      studied in experimentally carnitine-depleted or supplemented rats. 2. Muscle
      carnitine concentration can be decreased by 40% with D-carnitine and increased by
      40% with L-carnitine supplementation. 3. In spite of large variation of carnitine
      content, neither the exercising capacity nor the rate of muscle or liver
      glycogenolysis were modified during submaximal exercise. 4. The increased lipid
      metabolism induced by exercise can be adequately supported by endogenous levels
      of tissue carnitine. 5. Before any impairment in energy metabolism during
      exercise can be demonstrated, carnitine concentration has to be reduced to a
      level close to that measured with primary carnitine deficiency, i.e. less than 20
      mumol/l of plasma.

PMID- 1981036
TI  - Ionic conductances in two types of sensory neurons in the leech, Macrobdella
      decora.
AB  - 1. Ion conductances were investigated in two kinds of leech sensory neurons (PM
      and N1 cells) which differ in their membrane excitability and action potential.
      2. In the PM cell body excitable membrane behavior is dominated by only two
      currents, a sodium current (INa) and a delayed rectifier (IK). 3. In contrast, in
      the N1 cell INa and IK is supplemented with the presence of a transient potassium
      current, IA. 4. A comparison between INa and IK in the two cell types did not
      reveal any significant difference in activation and inactivation kinetics of
      either current between neurons. 5. Thus, the properties and presence of the A
      current in the N1 cell and not in the PM cell may account for the functional
      difference in excitability of the two kinds of neurons.

PMID- 1981037
TI  - Effects of recombinant human growth hormone in juvenile Nile crocodiles
      (Crocodylus niloticus).
AB  - 1. Recombinant human growth hormone (hGH) showed somatotropic activity in
      juvenile Nile crocodiles (Crocodylus niloticus). 2. Body weight of crocodiles
      receiving 3.25 micrograms hGH/g body weight twice a week was increased by 49%
      after five weeks of treatment, compared to 31% increase in controls. 3. Total
      length was increased by 15 and 5%, respectively, in the two groups. 4. Food
      conversion efficiency increased from 28% in the controls to 36% in the hormone
      injected animals. 5. Cessation of hormone treatment was followed by reduced
      appetite and decreasing body growth.

PMID- 1981038
TI  - The effect of long-term treatment by the angiotensin I-converting enzyme
      inhibitor enalapril on renal function and left ventricular hypertrophy in severe
      essential hypertension.
AB  - The therapeutic effect of long-term enalapril administration was studied in 20
      patients with severe essential hypertension (EH), resistant to intensive therapy
      with a combination of 3 or 4 antihypertensive drugs. Addition of enalapril
      (Renitec MSD from 5 to 40 mg/day) to the previous therapy allowed to maintain
      blood pressure within limits not exceeding 150/95 mmHg during a 12-month study in
      more than 80% of previously resistant patients. Left ventricular hypertrophy
      regressed in all patients and dilatation of the left ventricle seen in 4 patients
      disappeared during enalapril treatment. Serum sodium creatinine did not change
      significantly. Serum potassium increased slightly but remained within the normal
      range. Proteinuria had a tendency to diminish and N-acetyl-beta-D-glucosaminidase
      activity in the urine dropped within normal limits. Based on their results, the
      authors conclude that enalapril is suitable for the long-term treatment of
      patients with severe EH, resistant to intensive antihypertensive therapy, with
      minimal side effects, good tolerance and a tendency for amelioration of cardiac
      and renal function.

PMID- 1981039
TI  - Actions of excitatory amino acid antagonists on synaptic inputs to the rat medial
      vestibular nucleus: an electrophysiological study in vitro.
AB  - The actions of excitatory amino acid (EAA) antagonists on synaptic inputs to
      neurons in the rat medial vestibular nucleus (MVN) from ipsilateral vestibular
      afferents and vestibular commissures were studied in brain stem slice
      preparations. Antagonists used were 2-amino-5-phosphonovalerate (APV), a
      selective antagonist for the N-methyl-D-aspartate (NMDA) type of EAA receptors, 6
      cyano-7-nitroquinoxaline-2,3-dione (CNQX), a selective antagonist for the
      quisqualate/kainate (non-NMDA) type of EAA receptors and kynurenate (KYNA), a
      broad spectrum antagonist for the three types of EAA receptors. MVN neurons were
      classified as having mono- or polysynaptic inputs from vestibular afferents and
      commissural fibers by calculating synaptic delay. An application of APV through
      the perfusion medium suppressed 82% of cells activated monosynaptically from
      commissures, while it suppressed only 9% of cells activated monosynaptically from
      vestibular afferents. The application of KYNA proved much less selective,
      suppressing 83% of the former group of cells and 93% of the latter. CNQX
      suppressed almost all the cells of both groups. The sensitivity of monosynaptic
      inputs to KYNA, CNQX or APV was not significantly different from that of
      polysynaptic inputs irrespective of sources of inputs. These results suggest that
      excitatory synaptic inputs to MVN neurons are mediated mainly through non-NMDA
      type of EAA receptors from vestibular afferents and through NMDA as well as non
      NMDA types of EAA receptors from commissures.

PMID- 1981040
TI  - Role of NMDA and non-NMDA receptors in synaptic transmission in rat piriform
      cortex.
AB  - The pharmacology of synaptic transmission was studied in slices of rat piriform
      cortex using the selective non-NMDA glutamate receptor antagonist 6.7
      dinitroquinoxaline-2,3-dione (DNQX) and the selective NMDA receptor antagonist D
      2-amino-5-phosphonopentanoate (D-AP5). DNQX produced a dose-dependent blockade of
      synaptic transmission at both lateral olfactory tract and associational system
      synapses with half-maximal effects at about 2.5 microM. D-AP5 had no significant
      effects on field potentials recorded in medium containing 2.5 mM Mg++. However in
      low Mg++ (100-200 microM) medium, D-AP5 did reduce a slow component of
      postsynaptic responses in both synaptic systems. In Mg(++)-free medium, 20 microM
      DNQX did not completely block transmission; the remaining response components
      were blocked by D-AP5. These results suggest that normal synaptic transmission in
      the two main inputs to the superficial layers of piriform cortex is mediated by
      non-NMDA receptors but that NMDA receptors can also participate under conditions
      where the Mg++ block of the NMDA channel is alleviated.

PMID- 1981042
TI  - [A feldsher-midwife center worth its money].

PMID- 1981041
TI  - Comments to: P. Liesi, E.-M. Salonen, D. Dahl, A. Vaheri, and S.-J. Richards.

PMID- 1981043
TI  - Phobic anxiety and clumsiness in a 10-year-old girl.
AB  - During assessment of a girl with a long-standing phobic state, it was found that
      she also had previously unrecognised perceptuo-motor problems, which were
      associated with continuing problems in balance and spatial awareness. Her phobia
      improved after a desensitisation programme, but the physical disorder persisted,
      despite physiotherapy. The authors conclude that the girl's phobic anxiety may
      have had its origin in her experience of the perceptual disorder during
      development.

PMID- 1981045
TI  - [Comments on the contribution "Changes in T-cell subpopulations in normal
      pregnancy and in patients with spontaneous abortions" by C. J. Thaler, L. J.
      Behnken, H. D. Taubert].

PMID- 1981044
TI  - [Significance of neu-protein for prognosis of breast cancers].
AB  - In 147 primary breast carcinomas, over-expression of NEU-protein was detected
      immuno-histochemically. 20 tumours (13.6%) showed a positive reaction.
      Correlations with established prognostic factors, showed a significant
      relationship to unfavourable histological grading and negative oestrogen receptor
      status, as well as to the negative status of both oestrogen and progesterone
      receptors. However, no correlation could be demonstrated with the progesterone
      receptor alone. Only a trend without significance was demonstrated to the tumour
      size and proliferation rate-indicated by the Ki-67 antibody. No correlation
      existed to the status of the axillary nodes. Overexpression of NEU-protein proved
      to have a significant influence on the disease-free survival and overall survival
      in a median follow-up time of 31 months. Nevertheless, this could be shown only
      for tumours with metastasis in axillary nodes, but not for nodal negative
      tumours. A possible Longer follow-up time is necessary, to show a difference of
      results for the latter group.

PMID- 1981046
TI  - Behavioral and neuroendocrine response to psychosocial stress in male rats: the
      effects of the 5-HT 1A agonist ipsapirone.
AB  - The effect of the 5-HT 1A agonist ipsapirone on the behavior, plasma
      catecholamine, and corticosterone levels was studied in male Wistar rats during
      the psychosocial stress of confrontation with a confined dominant opponent 24 hr
      after defeat. The effect of the drug was also studied during a predefeat
      confrontation with the confined (would-be dominant) rat. Blood samples were
      withdrawn via a permanent heart catheter. The drug (5 mg/kg, ip) or vehicle was
      given 30 min before transportation to the experimental room. Ipsapirone had no
      major effects on the plasma hormone concentrations and had no influence upon the
      behavioral response to the confined rat. At the postdefeat test ipsapirone led to
      a significant increase of immobility, whereas both rearing and time spent
      sniffing the cage were diminished. Postdefeat psychosocial stress resulted in an
      increase of the hormone, particularly catecholamine levels. These responses were
      further elevated by the drug. The presence of high corticosterone levels in the
      home cage after postdefeat ipsapirone treatment leads to the hypothesis that
      postsynaptic 5-HT 1A receptor hypersensitivity develops after the social stress
      of defeat.

PMID- 1981048
TI  - Completion of the intron-exon structure of the gene for human type II procollagen
      (COL2A1): variations in the nucleotide sequences of the alleles from three
      chromosomes.
AB  - A new procedure for preparing cosmid libraries was used to isolate three alleles
      for the human gene for type II procollagen (COL2A1). Over 20,000 bp of one allele
      were completely sequenced and over 10,000 bp of the two other alleles were
      sequenced. The data located and defined 26 exons and introns of the gene not
      previously analyzed. The results completed the structure of the gene except for
      the newly discovered exon 2A that undergoes alternative splicing (Ryan et al.,
      1990, Trans. Ann. Meet. Orthop. Res. Soc. 15:65). As a result, it is the most
      completely known structure of a gene for a human fibrillar collagen. The results
      confirm the previous impression that exon sizes are highly conserved among the
      genes for the three major fibrillar collagens. Comparison of clones from the
      three alleles defined five neutral variations in coding sequences and seven
      variations in the intron that also are probably neutral variations. The normal
      sequences and the variations in sequences will be important for identifying
      different alleles and haplotypes of the gene and for the analysis of genetic
      mutations in the gene that cause diseases of cartilage such as chondrodysplasias
      and osteoarthritis.

PMID- 1981047
TI  - A physical linkage group in human chromosome band 11q23 covering a region
      implicated in leukocyte neoplasia.
AB  - Six genes on human chromosome band 11q23 have been linked by pulse-field gel
      electrophoretic analysis with the order cen-CD3E-CD3D-CD3G-PBGD-CBL2-THY1-qter.
      The corresponding long-range restriction map covers 1.8 Mb, the telomeric half of
      which (PBGD-CBL2-THY1) is localized to subband 11q23.3. Four genes (CD3E, CD3D,
      CD3G, and PBGD) can be positioned precisely, and with known transcriptional
      orientation, with respect to rare-cutter restriction sites. The linkage group
      covers a region implicated in leukocyte malignancy: several nonrandom neoplasia
      associated translocation chromosomes have breakpoints which separate the CD3
      genes from PBGD, CBL2, and THY1. Thus, we are able to localize such breakpoints,
      and consequently any affected candidate genes, to the 750 kb between CD3G and
      PBGD.

PMID- 1981049
TI  - A refined linkage map for DNA markers around the pericentromeric region of
      chromosome 10.
AB  - A refined genetic linkage map for the pericentromeric region of human chromosome
      10 has been constructed from data on 12 distinct polymorphic DNA loci as well as
      the locus for multiple endocrine neoplasia type 2A (MEN 2A), a dominantly
      inherited cancer syndrome. The map extends from D10S24 (at 10p13-p12.2) to D10S3
      (at 10q21-q23) and is about 70 cM long. Overall, higher female than male
      recombination frequencies were observed for this region, with the most remarkable
      female excess in the immediate vicinity of the centromere, as previously
      reported. Most of the DNA markers in this map are highly informative for linkage
      and the majority of the interlocus intervals are no more than 6 cM apart. Thus
      this map should provide a fine framework for future efforts in more detailed
      mapping studies around the centromeric area. A set of ordered cross-overs
      identified in this work is a valuable resource for rapidly and accurately
      localizing new DNA clones isolated from the pericentromeric region.

PMID- 1981050
TI  - Zinc finger protein gene complexes on mouse chromosomes 8 and 11.
AB  - Two murine homologs of the Drosophila Kruppel gene, a member of the gap class of
      developmental control genes that encode a protein with zinc fingers, were mapped
      to mouse chromosomes 8 and 11 by using somatic cell hybrids and an interspecific
      backcross. Surprisingly, both genes were closely linked to two previously mapped,
      Kruppel-related zinc finger protein genes, suggesting that they are part of gene
      complexes.

PMID- 1981051
TI  - Mapping of Col3a1 and Col6a3 to proximal murine chromosome 1 identifies conserved
      linkage of structural protein genes between murine chromosome 1 and human
      chromosome 2q.
AB  - We have investigated the degree of synteny between the long arm (q) of human
      chromosome 2 and the proximal portion of mouse chromosome 1. To define the limits
      of synteny, we have determined whether mouse homologs of seven human genes
      mapping to chromosome 2q cosegregated with anchor loci on mouse chromosome 1. The
      loci investigated were NEB/Neb, ELN/Eln, COL3A1/Col3a1, CRYG/Len-2, FN1/Fn-1,
      VIL/Vil, and COL6A3/Col6a3. Ren-1,2 and Acrg were included as two proximal mouse
      chromosome 1 anchor loci. The segregation of restriction fragment length
      polymorphisms at these loci was analyzed in the progeny of Mus spretus x C57BL/6J
      hybrids backcrossed to the C57BL/6J inbred strain. We found that five of the
      structural protein loci and the two anchor loci form a linkage group on proximal
      murine chromosome 1. The proposed gene order of this group of linked markers is
      centromere - Col3a1 - Len-2-Fn-1-Vil-Acrg-Col6a3-Ren1,2. Neb and Eln are linked
      neither to each other nor to any other marker on proximal mouse chromosome 1.
      Therefore, the mouse loci Col3a1 and Col6a3 are identified as flanking markers of
      the linkage group of structural protein loci. The estimated genetic map distances
      are Col3a1-13.3 cM-Len-2-3.4 cM-Fn-1-3.8 cM-Vil-9.6 cM-Acrg-2.1 cM-Col6a3-18.3 cM
      Ren1,2. The available map information for human chromosome 2q markers and mouse
      chromosome 1 markers presented here tentatively identifies Col3a1 and Col6a3 as
      the border markers that define the limits of the syntenic chromosome segment. The
      order of mouse genes on chromosome 1 and their human homologs on chromosome 2q
      also appears to be conserved, suggesting that mapping of murine genes on the
      conserved segment may be useful to predict gene order in man.

PMID- 1981052
TI  - Molecular and cytogenetic analysis in two patients with microdeletions of 7p and
      Greig syndrome: hemizygosity for PGAM2 and TCRG genes.
AB  - Greig cephalopolysyndactyly syndrome (GCPS) is an autosomal dominant disorder
      that has been mapped to 7p13. We have investigated two patients with GCPS and a
      cytogenetically visible microdeletion of the short arm of chromosome 7 with gene
      probes that have been assigned close to the proposed Greig locus. Deletion
      breakpoints were determined from high-resolution G- and R-banded chromosomes. In
      patient BC with a de novo deletion (7p12.3-7p14.2) we have found a loss of the
      genomic region containing the T-cell receptor gamma (TCRG) gene cluster, whereas
      the other patient IR with a deletion (7p11.2-7p13) due to a de novo translocation
      was apparently normal for this region. Gene dosage analysis revealed a loss of
      the phosphoglycerate mutase muscular form (PGAM2) gene locus in both patients.
      Hox 1.4 and interferon-beta 2 (IFNB2) showed a normal gene dosage. Our
      investigations revealed the following ordering and assignments of the studied
      genes: PGAM2 and GCPS in 7p12.3-13; TCRG in the distal part of 7p13-7p14.2; Hox
      1.4 and IFNB2 distal to 7p14.2. Our results suggest a location of the TCRG gene
      more proximal than that reported previously. Furthermore, we were able to exclude
      the Hox 1.4 gene from involvement in the pathogenesis of GCPS.

PMID- 1981053
TI  - Molecular genetic markers spanning mouse chromosome 10.
AB  - Somatic cell hybrids, recombinant inbred (RI) strains, and progeny of an
      intersubspecific backcross were typed by Southern blot analysis to prepare a
      linkage map of mouse chromosome 10. The seven genetic markers in this map, four
      of which had not previously been positioned, include genes involved in
      oncogenesis (Gli, Myb, Tra-1), proviral integration (Emv-25), and immune
      responses (Ifg, Ifgr, Pfp). The linkage map spans much of the chromosome and
      covers a region of the mouse genome with few molecular markers. The gene order
      established here demonstrates that the genes for murine interferon-gamma (Ifg)
      and its receptor (Ifgr) are at opposite ends of the chromosome and that Ifgr and
      the Myb oncogene are closely linked, a factor that may be related to their joint
      transcriptional enhancement in some plasmacytoid lymphosarcomas.

PMID- 1981054
TI  - A molecular genetic linkage map of mouse chromosome 7.
AB  - The homology between mouse chromosome 7 and human chromosomes 11, 15, and 19 was
      examined using interspecific backcross animals derived from mating C3H/HeJ
      gld/gld and Mus spretus mice. In an earlier study, we reported on the linkage
      relationships of 16 loci on mouse chromosome 7 and the homologous relationship
      between this chromosome and the myotonic dystrophy gene region on human
      chromosome 19. Segregation analyses were used to extend the gene linkage
      relationships on mouse chromosome 7 by an additional 21 loci. Seven of these
      genes (Cyp2a, D19F11S1h, Myod-1, Otf-2, Rnu1p70, Rnu2pa, and Xrcc-1) were
      previously unmapped in the mouse. Several potential mouse chromosome 7 genes
      (Mel, Hkr-1, Icam-1, Pvs) did not segregate with chromosome 7 markers, and
      provisional chromosomal assignments were made. This study establishes a detailed
      molecular genetic linkage map of mouse chromosome 7 that will be useful as a
      framework for determining linkage relationships of additional molecular markers
      and for identifying homologous disease genes in mice and humans.

PMID- 1981055
TI  - Localization of the gene for the trans-acting transcription factor Sp1 to the
      distal end of mouse chromosome 15.
AB  - The mouse chromosomal location for the gene (Sp1-1) encoding the trans-acting
      transcription factor Sp1 has been determined. Analysis of restriction fragment
      length polymorphisms in recombinant inbred, congenic, and interspecific backcross
      mice using human and mouse cDNA probes demonstrated that Sp1-1 is a single gene
      closely linked to the mammary tumor virus integration site-1 (Int-1) on the
      distal end of chromosome 15. Sp1 is a zinc finger protein, but Sp1-1 is not
      closely linked to any of the other zinc finger protein genes that have been
      mapped in mouse. Int-1 and other markers flanking the Sp1-1 locus are part of a
      conserved linkage group represented on human chromosome 12q.

PMID- 1981056
TI  - Genetic mapping of the gene for Ca2+/calmodulin-dependent protein kinase IV (Camk
      4) to mouse chromosome 18.
AB  - Southern blot analysis of Chinese hamster x mouse somatic cell hybrids was used
      to map the gene for a serine/threonine protein kinase expressed in brain and
      testis. This locus, termed Camk-4, encodes Ca2+/calmodulin-dependent protein
      kinase IV. Progeny of an interspecific backcross were analyzed to position Camk-4
      in the centromeric region of chromosome 18 near two mutations known to affect
      neurological function and fertility. This raises the possibility that a defect in
      Camk-4 may be responsible for one of these mutant phenotypes.

PMID- 1981058
TI  - Clone and genomic repositories at the American Type Culture Collection.

PMID- 1981059
TI  - [Symposium: Drug therapy of cardiac insufficiency. Padova, 12-14 October 1990].

PMID- 1981057
TI  - The Pit-1 transcription factor gene is a candidate for the murine Snell dwarf
      mutation.
AB  - Two nonallelic mouse mutations with severe dwarf phenotypes are characterized by
      a lack of growth hormone, prolactin, and thyroid stimulating hormone. The cells
      that normally synthesize these pituitary hormones express a common transcription
      factor called GHF-1 or Pit-1. Using an intersubspecific backcross, we have
      demonstrated tight linkage of the Pit-1 and Snell dwarf (dw) genes on mouse
      chromosome 16. No recombination was observed between Pit-1 and dw in 110
      individuals examined. Southern blot analysis of genomic DNA reveals that the Pit
      1 gene is rearranged in C3H/HeJ-dwJ/dw mice but not in coisogenic +/+ animals,
      providing molecular evidence that a lesion in the Pit-1 gene results in the Snell
      dwarf phenotype. Demonstration of low levels of Pit-1 expression in Ames dwarf
      (df) mice implies that both Pit-1 and df expression may be required for pituitary
      differentiation.

PMID- 1981060
TI  - HLA-DQA2 (DX alpha) polymorphism and insulin dependent diabetes.
AB  - A certain HLA-DQA2 locus TaqI fragment, DX alpha"U", has been reported to be
      associated with insulin-dependent diabetes mellitus (IDDM). Reports of various
      studies in this vein have ranged from stating that the association of DQA2"U"
      with IDDM exists even among subjects positive for HLA-DR3 and -DR4 to stating
      that the association of DQA2"U" with diabetes can be attributed to linkage
      disequilibrium between the DQA2"U" and some component(s) on the affected
      haplotypes. Using a synthetic 97-base probe corresponding to a portion of an
      intron of DQA2, in a Southern blot analysis of IDDM and control subjects from
      Wisconsin, we were able to confirm the association of DQA2"U" with diabetes.
      However, among DR3 subjects there was no significant association between DQA2"U"
      and diabetes (p = 0.26). Although there was a (nonsignificant) association of
      IDDM with DQA2"U" among DR4-positive subjects (p = 0.14), this can be completely
      attributed to linkage disequilibrium between DQA2"U" and DQw8. We also sequenced
      most of the second exon (corresponding to the alpha 1 domain of the DQA2
      glycoprotein) from five individuals that were homozygous for either DQA2"U" or
      DQA2"L." The only polymorphisms observed were a "silent" mutation at position 36
      and one example of a difference that would result in a change of amino acid at
      position 41.

PMID- 1981062
TI  - Control of prostaglandin-induced parturition in sows by injection of the beta
      adrenergic blocking agent carazolol or carazolol and oxytocin.
AB  - Although parturition commonly is induced in swine with prostaglandin F2 alpha or
      one of its analogs, variation in response to the treatment is large. The purpose
      of this investigation was to more precisely terminate parturition. Two
      experiments were conducted. Sows all received prostaglandin analog followed, 20 h
      later, by different doses of the beta-adrenergic blocking agent carazolol and(or)
      oxytocin. Treatment with 3 mg of carazolol alone caused parturition to commence
      within 2.6 +/- .23 (SEM) h after injection. Parturition was complete in 2.0 +/-
      .13 h and proceeded smoothly without the necessity of manual assistance. Adding
      2.5 I.U. of oxytocin to the 3 mg of carazolol speeded the onset of labor (1.7 +/-
      .17 h). However, in some cases parturition was interrupted and the time passing
      between the birth of the first and the last piglet was prolonged to 2.5 +/- .28
      h. We conclude that by applying carazolol 20 h after a prostaglandin analog,
      parturition in swine may be terminated very effectively.

PMID- 1981061
TI  - Major histocompatibility complex genes influence the outcome of HIV infection.
      Ancestral haplotypes with C4 null alleles explain diverse HLA associations.
AB  - Several alleles at multiple HLA loci have been found to be associated with
      infection with human immunodeficiency virus (HIV): HLA A1; B8, B35; Cw7, Cw4;
      DR1, DR3 and DQ1, are associated with particular disease manifestations and/or
      disease progression. Furthermore, in a pilot study we have shown an increase in
      the frequency of C4 null alleles and suggested that all the reported HLA alleles
      could reflect association with a limited number of ancestral haplotypes (AHs). On
      this occasion, we studied 122 Caucasoid patients classified according to Centers
      for Disease Control (CDC) criteria. The control group consisted of 67
      seronegative homosexual or bisexual males at risk of developing HIV infection. C4
      null alleles were unequivocally present in 58% of patients in CDC IV compared
      with 33% of the seronegative subjects (chi 2 = 5.65, p less than 0.05).
      Furthermore, C4 null alleles could be excluded in only 8% and 16% of CDC III and
      IV, respectively, but in 30% of the seronegative subjects. An increased frequency
      of three AHs largely accounted for the increases in C4 null and HLA alleles. To
      examine the role of specific AHs we undertook a longitudinal analysis of a
      subgroup of 26 patients who seroconverted under observation. Seventeen of these
      patients were followed for 32 to 63 months. All seven patients with the 8.1 AH
      (A1, CW7, B8, BfS, C4AQ0, C4B1, DR3, DQ2) developed low CD4 lymphocyte counts
      (less than 450 x 10(6)/l) compared with only 2 of 10 patients without this
      haplotype (p less than 0.002). All three deaths occurred in patients with the 8.1
      AH. The acquired immunodeficiency syndrome developed in three further cases with
      either 8.1- or B35-bearing (35.x) haplotypes. Sequential CD4/8 ratios showed an
      early and progressive decline in individuals with 8.1 or 35.x. Since the 8.1 and
      35.x AHs contain deletions of the central major histocompatibility complex (MHC)
      genes, we suggest that the genes affecting HIV infection and progression are
      within the central MHC region.

PMID- 1981063
TI  - Ofloxacin--developments in therapy. Third International Symposium on Ofloxacin.
      Scheveningen, The Netherlands, 26-27 April 1990.

PMID- 1981064
TI  - On the meaning of Maslach's three dimensions of burnout.
AB  - The dimensionality of Maslach's (1982) 3 aspects of job burnout--emotional
      exhaustion, depersonalization, and personal accomplishment--was examined among a
      sample of supervisors and managers in the human services. A series of
      confirmatory factor analyses supported the 3-factor model, with the first 2
      aspects highly correlated. The 3 aspects were found to be differentially related
      to other variables reflecting aspects of strain, stress coping, and self-efficacy
      in predictable and meaningful ways. Implications for better understanding the
      burnout process are discussed.

PMID- 1981065
TI  - Isolation and partial characterization of angiotensinase A and aminopeptidase M
      from urine and human kidney by lectin affinity chromatography and high
      performance liquid chromatography.
AB  - Angiotensinase A (ATA) and aminopeptidase M (APM) were partially purified from
      human urine specimens and human kidney particles using wheat germ lectin affinity
      chromatography, anion-exchange Fast Protein Liquid Chromatography (FPLC) (Mono
      Q), chromatofocusing (Mono P, FPLC) and Superose 12 gel filtration. APM, a
      globular 5-nm glycoprotein, is localized in the brush border membrane of the
      proximal tubule; angiotensin II-degrading ATA is present on glomerular endothelia
      and podocytes and, to lesser extent, in the brush border. For the first time,
      both peaks of ATA and APM activity from urine samples were separated by the above
      mentioned techniques with only slight overlap; ATP (146,000 dalton: pI4.8) was
      enriched more than 20-fold and APM (153,000 dalton, pI4.7) more than 50-fold
      compared with the activity of the starting material. Using similar separation
      steps, ATA and APM solubilized from kidney particles could not be resolved into
      two distinct peak fractions, however, except after hydrophobic interaction
      chromatography. Thus urine is a major source for the preparation of individual
      ATA and APM fractions, necessary to generate specific anti-enzyme antibodies for
      diagnostic purposes.

PMID- 1981066
TI  - [Recent advance in the treatment of hypertension].

PMID- 1981067
TI  - Relative abuse liability of different benzodiazepines in drug abusers.
AB  - There is a convergence of data from various sources suggesting that there are
      meaningful differences among the benzodiazepines with respect to their
      attractiveness as drugs of abuse for drug abusers. Laboratory studies of
      subjective and reinforcing effects in drug abusers, interviews with drug abusers,
      clinical judgment of medical professionals, and epidemiological studies all
      indicate that diazepam, in particular, has a greater abuse liability than many of
      the other benzodiazepines. Some of the available data also suggest that lorazepam
      and alprazolam are more diazepam-like in having relatively high abuse liability,
      while oxazepam, halazepam, and possibly chlordiazepoxide, are relatively low in
      this regard. These differences in abuse liability among benzodiazepines are
      analogous to the widely recognized differences in abuse liability within the
      barbiturate class that have proved to be important in helping guide clinicians'
      drug prescribing practices.

PMID- 1981068
TI  - Zuclopenthixol: a new generation of antipsychotic drugs. An open clinical trial.
AB  - Fifteen patients (20-49 years of age) with mania or acute psychosis were treated
      with zuclopenthixol acetate (Clopixol, Acuphase). One injection of 75-100 mg
      produced significant amelioration of psychotic symptoms with minimal side
      effects. The duration of action of the drug was found to be about 72 hours.

PMID- 1981069
TI  - Can bright light be conceptualized as a pharmacological treatment?

PMID- 1981070
TI  - Nifedipine in the treatment of tardive dyskinesia.
AB  - There have been several case reports of improvement in tardive dyskinesia (TD)
      after treatment with calcium-blocking agents. We have conducted prior single
      blind (rater-blind) studies of verapamil and diltiazem and found a statistically
      significant improvement in TD with verapamil, and a small improvement that did
      not reach statistical improvement after diltiazem treatment. We now report a
      single-blind (rater-blind) study of a third calcium antagonist, nifedipine, in
      the treatment of TD. Nifedipine (30-60 mg/day) was administered to eight
      schizophrenic patients with TD. Mean AIMS scores on items 1-7 decreased from 12.9
      +/- 2.0 (SD) at baseline to 10.8 +/- 2.7 after treatment (t = 3.66, p = 0.01).
      All subjects were able to tolerate the maximal dose of nifedipine without
      significant side effects. TD is known to be affected by drugs that affect
      dopamine neurotransmission. Several lines of pre-clinical and clinical evidence
      suggest interactions between the calcium antagonists and the CNS dopamine system
      and provide a possible explanation for the effects on TD seen with calcium
      antagonists.

PMID- 1981071
TI  - Serum SLX levels in patients with non tumoral pathologies. Our experience in 189
      cases.

PMID- 1981073
TI  - Managing coronary heart disease risk in hypertensive smokers. Report of a
      symposium. Hong Kong. 16 February 1990.

PMID- 1981072
TI  - [Five cases of listeriosis in the elderly].
AB  - We reported five cases of listeriosis (sepsis and meningitis) in the elderly in
      our hospital during the last 4 years, where no cases of listeriosis had been
      found. These 5 cases had diabetes mellitus, lung cancer, chronic respiratory
      failure, gastric ulcer and aplastic anemia respectively as their underlying
      diseases. At the onset of listeriosis, 3 cases received corticosteroid and 3
      cases received H2-blocker. 2 patients were cured and 3 patients died. Three
      autopsy cases had meningitis or meningoencephalitis and 2 cases of these autopsy
      cases had granulomatous changes in these spleens. In serotypes of Listeria
      monocytogenes (L. monocytogenes), 4 cases were 4b and 1 cases was 1b. All 5
      strains were resistant to 3rd generation cephems. Wide uses of 3rd generation
      cephems and H2-blocker may be one of the reasons for the recent increase of
      listeriosis. Ingestion of contaminated food is the pathogenetic mechanism for
      initiating L. monocytogenes infections. And following the change of eating habits
      and the increase of imported foods, food-born listeriosis may increase. We
      suppose the increase of L. monocytogenes infections and must give attention to L.
      monocytogenes infections.

PMID- 1981074
TI  - Acute effects of doxazosin and atenolol on smoking-induced peripheral
      vasoconstriction in hypertensive habitual smokers.
AB  - The acute effects of selective alpha 1 inhibition with doxazosin (0.5-0.7 mg
      intravenously) and beta 1-blockade with atenolol (0.1 mg/kg body weight,
      intravenously) on smoking-induced peripheral vasoconstriction were investigated
      in 24 hypertensive habitual smokers. Forearm blood flow was measured by venous
      occlusion plethysmography and skin blood flow was estimated by thermography and
      laser doppler flowmetry. After the patients had smoked two cigarettes, plasma
      adrenaline elevations were similar under basal conditions and after drug
      administration; plasma noradrenaline remained unchanged. The smoking-induced
      increase in the heart rate was attenuated by atenolol compared with basal values.
      The smoking-induced increase in systolic blood pressure was more marked after
      atenolol and doxazosin (P less than 0.05) than before the drug administration.
      The smoking-induced increase in diastolic blood pressure was enhanced by atenolol
      (P less than 0.05) but unchanged by doxazosin. Smoking increased forearm vascular
      resistance under basal conditions (P less than 0.05) and after atenolol (P less
      than 0.01) but not after doxazosin. Similarly, skin temperature was significantly
      reduced by smoking under basal conditions and after the administration of
      atenolol (P less than 0.001) but not doxazosin. The smoking-induced reduction in
      skin blood flow was attenuated by doxazosin compared with atenolol (P less than
      0.05). Thus, smoking-induced muscular and cutaneous vasoconstriction was
      inhibited by doxazosin as opposed to atenolol in hypertensive habitual smokers.
      This may reflect unmasked beta-adrenoceptor mediated vasodilation in addition to
      attenuated alpha 1-adrenoceptor mediated vasoconstriction.

PMID- 1981075
TI  - Blood pressure and heart rate response to repeated smoking before and after beta
      blockade and selective alpha 1 inhibition.
AB  - In normotensive volunteers who habitually smoked more than 20 cigarettes a day, 1
      h beat-to-beat blood pressure recordings were taken. Measurements were made using
      a non-invasive finger device when the subjects were not smoking (1 h, control)
      and during an hour in which the subjects were asked to smoke four cigarettes, one
      every 15 min. The first cigarette smoked produced a marked increase in systolic
      and diastolic blood pressures and the heart rate. The peak blood pressure and
      heart rate values observed for the first cigarette did not change when the
      remaining three cigarettes were smoked, indicating that the responses were
      neither attenuated nor increased by repeated smoking. However, after each
      cigarette, the pre-smoking values did not return to baseline, but were
      successively greater for the second, third and fourth cigarettes, indicating that
      blood pressure and the heart rate undergo a persistent increase during smoking.
      Compared with the hour-long non-smoking period, mean values over the smoking
      period were 18.8%, 14.0% and 29.7% higher for systolic and diastolic blood
      pressure and the heart rate, respectively. Cigarette smoking also increased the
      blood pressure and heart rate standard deviations around the mean, thereby
      increasing the variability. The effects of atenolol and doxazosin on the blood
      pressure and heart rate responses to smoking were investigated in two placebo
      controlled, single-blind, randomly allocated, crossover studies. Compared with
      placebo, atenolol (50-100 mg given once a day for 4 days) significantly
      attenuated the smoking-induced increase in the heart rate but not the increase in
      systolic or diastolic blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1981076
TI  - Selective alpha 1 inhibition with doxazosin in hypertensive smokers and non
      smokers: haemodynamic and metabolic effects.
AB  - Hypertensive cigarette smokers have an especially high risk of coronary heart
      disease. Doxazosin, which has beneficial effects on haemodynamic factors and
      lipid metabolism, may be suitable for treating these patients. The haemodynamic
      and metabolic effects of doxazosin were investigated in a 16-week open, parallel,
      comparative study of 64 heavy cigarette smokers and 69 non-smokers after a 4-week
      placebo period. Of the 133 patients who entered, six patients (one smoker and
      five non-smokers) withdrew due to adverse events. Doxazosin significantly reduced
      blood pressure without reflex tachycardia in both the smokers and the non
      smokers. The therapeutic success rates (reduction in sitting diastolic blood
      pressure to less than or equal to 90 mmHg and greater than or equal to 5 mmHg
      reduction, or greater than or equal to 10 mmHg reduction from baseline) were
      similar for the smokers (93.3%) and the non-smokers (92.5%). Doxazosin
      significantly decreased total cholesterol and low-density lipoprotein (LDL)
      cholesterol, but increased high-density lipoprotein (HDL) cholesterol and the
      HDL:total cholesterol ratio in both smokers and non-smokers. Doxazosin corrected
      the reduction in HDL cholesterol caused by smoking; compared with baseline,
      doxazosin increased HDL cholesterol by 19% in hypertensive smokers. The
      beneficial effects of doxazosin on blood pressure and the lipid profile were
      apparent in the change in the 10-year probability of developing coronary heart
      disease as calculated by the Framingham equation; the calculated risk of coronary
      heart disease decreased by 39% in smokers and by 33% in non-smokers. Plasma
      fibrinogen and plasminogen activator inhibitor, which independently contribute to
      atherosclerosis, were significantly reduced by doxazosin in the non-smokers but
      not in the smokers.

PMID- 1981077
TI  - Long-term effects of doxazosin and atenolol on serum lipids and blood pressure in
      hypertensive smokers.
AB  - On the basis of a 1-year double-blind comparative study of doxazosin and atenolol
      in hypertensive patients, we have previously described sustained and
      significantly different drug effects on the blood lipid profile. The present
      paper presents a retrospective analysis of the smoking subgroups for each drug
      regimen, for both the original 12-month double-blind period and for a further 12
      month open-label period. The changes in blood lipids were qualitatively and
      quantitatively similar in both the smoking subgroup and in the full study
      population (smokers and non-smokers). In the hypertensive smokers doxazosin
      increased high-density lipoprotein (HDL) cholesterol (+9.4%) and decreased
      triglycerides (-10.9%) whereas atenolol had the opposite effect, decreasing HDL
      cholesterol (-5.6%) and increasing triglycerides (+20.7%). The antihypertensive
      effects of doxazosin (n = 24) and atenolol (n = 23) were comparable over 24
      months of treatment. Eighteen (75%) doxazosin and 17 (73.9%) atenolol patients
      reached the blood pressure goal (sitting diastolic blood pressure less than or
      equal to 90 mmHg with at least a 5-mmHg reduction, or a greater than or equal to
      10-mmHg reduction from baseline). As a consequence of the lowered blood pressure
      and favourable lipid changes, doxazosin decreased the risk of coronary heart
      disease (as calculated from the Framingham risk equation) by -24.4% (P less than
      0.05). However, the calculated risk was not significantly reduced by atenolol (
      2.1%). It is concluded that the smoking status of the patient has no obvious
      implications for the safety, efficacy or metabolic effects of doxazosin.

PMID- 1981078
TI  - Induction and upregulation of adhesion receptors in oral and dermal lichen
      planus.
AB  - The expression pattern of well-defined cell surface adhesion receptors called VLA
      family, LFA-1 and ICAM-1 was determined semiquantitatively in biopsies of oral (n
      = 12) and dermal lichen planus (n = 5) and compared to normal uninvolved human
      oral mucosa (n = 12) and skin (n = 12) using an indirect immunoperoxidase
      technique. In both oral and dermal lichen planus, an induction of the beta 1
      integrins VLA-1 and VLA-3 and an upregulation of VLA-6 was found in T cells
      infiltrating the basement membrane zone. These cell surface molecules function as
      receptors for collagen, fibronectin and laminin. A focal induction of ICAM-1 on
      basal keratinocytes could be detected at sites of intramucosal T cells. These
      results suggest that investigated adhesion receptors are crucially involved in
      the aggregation of T cells in both conditions. Further investigations have to be
      done to determine the functional role of these adhesion receptors in lichen
      planus.

PMID- 1981079
TI  - Epidemiology, clinical features and prognostic value of HIV-1 related oral
      lesions.
AB  - Between February 1987 and February 1990, we studied 737 antibody anti HIV-1
      positive (AbHIV+) subjects referred to the Infectious Diseases Institute of the
      University of Turin (Italy) in order to evaluate types, prevalences, relations
      with clinical stages, distributions in risk-groups and prognostic significances
      of HIV-1 related oral lesions. The study evidenced the high prevalence of oral
      lesions, especially mycoses, in the investigated population: 40.3% of the
      patients showed, in fact, HIV-1 related oral lesions. The 37 months follow-up of
      55 AbHIV+ with oral hairy leukoplakia (HL) and 101 patients with oral candidiasis
      (OC), demonstrated that the probability of developing AIDS in patient with HL was
      0.381 at 15, 0.635 at 25 and 0.824 at 37 months. In the patients with OC the
      probability was 0.294 at 15 months, 0.524 at 25 and 0.781 at 37 months.

PMID- 1981080
TI  - Akathisia. When treatment creates a problem.
AB  - 1. Akathisia is a state of restlessness and motor agitation, which includes
      subjective feelings of inner tension, emotional unease, anxiety, a constant need
      to move, restless motor activity, and an inability to tolerate inactivity or
      rest. 2. Akathisia is often unrecognized or misdiagnosed as agitation or anxiety
      of psychiatric origin; this often leads to inappropriate increases in the
      antipsychotic dosage, which then potentiates its severity, or to the misuse of
      antianxiety agents, which masks symptoms. 3. Akathisia can be easy to recognize
      by simple clinical observation of the patient's behaviors, especially if the
      symptoms worsen after increases in antipsychotic dosages or the frequent use of
      as needed medications. Assessment must also include the patient's own report.

PMID- 1981081
TI  - [The activity of gamma glutamyltransferase in the urine of sheep].
AB  - The activity of gamma glutamyltransferase (GGT) was measured in sheep urine using
      a method developed for the routine assay of serum. Despite variation in urine pH
      and specific gravity, this method gave reproducible results. Serial dilutions of
      urine samples to which bovine GGT extract was added, showed a linear relationship
      for GGT values between 48 U l-1 and 373 U l-1. When a saline solution of GGT was
      added to urine and serum to compare the behaviour of GGT in the two fluid
      mediums, no difference could be demonstrated. The presence of non-specific enzyme
      inhibitors for GGT in sheep urine could not be established, eliminating the need
      for urine dialysis before the assessment of GGT activity. GGT activity remained
      the same in urine samples that were stored at 4, 25 and -20 degrees C for 12 and
      24 hours. Serial urine samples from 16 sheep were collected for 24 hours and the
      activity of GGT and the creatinine concentration were measured. Although there
      was significant variation in the measured GGT and creatinine values, the ratio of
      GGT:creatinine remained constant. The mean urine GGT:creatinine ratio was found
      to be 29.1 with a standard deviation of 7.0. A population reference value for
      urine GGT: urine creatinine ratio in clinically normal sheep was calculated to be
      43.1.

PMID- 1981082
TI  - Pharmacokinetics of intravenously, intramuscularly and intra-adiposely
      administered carazolol in pigs.
AB  - The beta-blocking agent carazolol is used for the prevention of stress syndromes
      in pigs. Little is known of the pharmacokinetics of this drug, and therefore of
      its residue status in meat. In this study carazolol pharmacokinetics were
      investigated in a randomized three-way cross-over design in five pigs. A dose of
      0.025 mg/kg was given intravenously, intramuscularly and intra-adiposely (in the
      subcutaneous fat layer). Carazolol was rapidly distributed and had a short half
      life of 1.2-4.2 h. The distribution volume was calculated to be 0.22-0.65 l/kg.
      After intramuscular or intra-adipose administration the absorption pattern was
      biphasic. A rapid initial phase was followed by a slow second phase. Absorption
      was found to be incomplete at 24 h after intramuscular and intra-adipose
      administration ranging from 24 to 59% and 25 to 66%, respectively. The biphasic
      behaviour could be explained by retention of the drug in the tissues after
      absorption of the solvent was complete. A few hours after intravenous
      administration only negligible amounts of the drug were circulating in the body;
      however, considerable amounts of drug might have remained at the intramuscular or
      intra-adipose injection site.

PMID- 1981083
TI  - Experience with anti-hypertensive drug therapy in a hypertension clinic--1972
      1983. A retrospective analysis.
AB  - Retrospective experience with drug therapy in 747 patients with essential
      hypertension registered from 1972-1983 is reported. Five hundred patients were
      seen between 1972 to 1978 and 247 between 1979-1983; the latter group was
      characterised by the use of beta blockers as first line drugs. Hypertension was
      graded according to level of diastolic blood pressure as mild, moderate and
      moderately severe or severe in 423, 211, and 113 patients, respectively. The
      overall response to treatment at 6 months was satisfactory in 66.2% of mild,
      50.2% of moderate and 58.4% of severe grades of hypertension. A large number of
      patients in both the groups having varying grades of severity needed at least 2
      to 3 drugs for the control of hypertension. The side effects of drugs were
      generally mild which included general weakness with diuretics; skin rash, nasal
      congestion and pruritus with methyldopa; cold extremities with beta blockers and
      palpitations with prazosin.

PMID- 1981084
TI  - [Results of the conservative treatment of urinary incontinence in women].
AB  - We reviewed 115 incontinent women undergoing conservative treatment. Urinary
      incontinence was caused by pelvic floor weakness (genuine stress incontinence) in
      54 patients, by involuntary detrusor contraction (detrusor instability) in 38 and
      by both (mixed type) in 23. Tricyclic antidepressants or alpha-adrenergic
      stimulators were given to 30 patients with pelvic floor weakness; Incontinence
      disappeared in 4 patients (13%) and was improved in other 3 patients (10%).
      Twenty-two patients with pelvic floor weakness underwent pelvic floor exercise
      with or without medication; Incontinence disappeared in 8 patients (36%) and was
      improved in other 11 patients (50%). The presence or absence of medication did
      not affect the results. Twenty-eight patients with involuntary detrusor
      contraction underwent bladder training combined with medication of detrusor
      relaxants. Incontinence disappeared in 4 patients (14%) and was improved in other
      13 patients (46%); There was no significant difference in the results between
      smooth muscle relaxants and tricyclic antidepressants. Of the 23 patients with
      mixed type, 11 underwent bladder training with medication; Incontinence
      disappeared in 2 patients (18%) and was improved in 3 patients (27%). The
      remaining 11 patients received medication, pelvic floor exercise or urethral
      dilatation, and only 2 patients were cured or improved of incontinence. Follow-up
      of the patients with involuntary detrusor contraction or mixed type showed that
      urinary incontinence tended to recur after discontinuation of medication. These
      results indicate that incontinent women with pelvic floor weakness should be
      treated first with pelvic floor exercise, and then with bladder training with
      medication. Although it has only a limited effect, it is an acceptable treatment
      of urinary incontinence caused by involuntary detrusor contraction.

PMID- 1981085
TI  - The right to refuse treatment: an application of the economic principles of
      decision-making under uncertainty.
AB  - When courts do not defer to professional medical judgement alternative ways must
      be found to make treatment decisions for persons who are deemed incompetent.
      Rather than impose the preferences of society upon the mentally ill individual,
      US courts favoured alternative procedures such as substituted judgement and the
      principle of the patient's best interest.

PMID- 1981086
TI  - Developmental-stage-specific plasmid supercoiling in Chlamydia trachomatis.
AB  - Chlamydia trachomatis elementary body (EB) and reticulate body (RB) developmental
      stages have polymorphic plasmid DNA. Several plasmid forms separated by gel
      electrophoresis were identified as topoisomers by treatment with topoisomerase I.
      Among these topoisomers was one form unique to EBs and one form unique to RBs.
      The unique EB plasmid topoisomer was characterized as highly supercoiled, on the
      basis of band migrations by gel electrophoresis and its appearance by electron
      microscopy. The unusual physical state of this topoisomer was probably mediated,
      in part, by DNA-specific structural proteins. The unique RB plasmid topoisomer
      was a supercoiled form of lower superhelical density than the other identified
      topoisomers. Developmental-stage-specific differences in super-helical density of
      plasmid DNA suggest cause-and-effect relationships between DNA topology and
      metabolic activity in RBs and metabolic quiescence in EBs.

PMID- 1981087
TI  - Studies on Clostridium acetobutylicum glnA promoters and antisense RNA.
AB  - The Clostridium acetobutylicum glnA gene has two transcript start sites under the
      control of promoters p1 and p2. Initiation of transcription was regulated by
      nitrogen and a downstream region was implicated in the regulation of transcript
      initiation by nitrogen in Escherichia coli. Putative antisense RNA was produced
      from a single downstream transcript start site under the control of p3. An up
      promoter mutation in p3 resulted in lower levels of glutamine synthetase (GS)
      activity. Putative antisense RNA had a role in down-regulating GS expression but
      was not involved in regulation by nitrogen. Deletion of downstream inverted
      repeat sequences resulted in very low levels of GS activity.

PMID- 1981089
TI  - [44th National Congress of the Italian Society of Anesthesia, Analgesia, and
      Resuscitation and Intensive Care. S. Margherita di Pula, October 22-26, 1990].

PMID- 1981088
TI  - Characterization of a Mycobacterium tuberculosis insertion sequence belonging to
      the IS3 family.
AB  - A repetitive element (IS986), previously isolated from Mycobacterium tuberculosis
      and shown to detect multiple restriction fragment-length polymorphisms (RFLPs),
      has been sequenced. It consists of a potential insertion sequence of 1358bp, with
      30-bp inverted repeat ends. IS986 has four potentially significant open reading
      frames (ORFs): ORFa1, ORFa2 and ORFb on one strand and ORFc on the complementary
      strand. The sequences of the potential translated products identify IS986 as a
      member of the IS3 family, with an apparent frameshift between ORFa1 and ORFa2.
      IS986 has potential as a highly specific probe for detection and typing of M.
      tuberculosis, as well as for transposon mutagenesis of mycobacteria. The sequence
      of IS986 is virtually identical to that of another recently described element,
      IS6110 (Thierry et al., 1990).

PMID- 1981090
TI  - [Neurochemistry of the posterior column of the spinal cord].

PMID- 1981091
TI  - Involvement of the amygdaloid complex in neuromodulatory influences on memory
      storage.
AB  - Neuromodulatory systems activated by training experiences appear to play a role
      in influencing memory storage processes. The research summarized in this paper
      examined the effects, on memory, of posttraining administration of treatments
      affecting adrenergic, opioid peptidergic and GABAergic systems. When administered
      after training, drugs affecting these systems all produce dose- and time
      dependent effects on memory storage. The drug effects on memory are blocked by
      lesions of the amygdaloid complex as well as lesions of the stria terminalis, a
      major amygdala pathway. The effects of drugs affecting these neuromodulatory
      systems are also blocked by injections of beta-adrenergic antagonists
      administered to the amygdaloid complex. Thus, the findings suggest that the
      neuromodulatory systems affect memory storage through influences involving the
      activation of beta-adrenergic receptors within the amygdala. These findings are
      consistent with the view that the amygdala is involved in regulating the storage
      of memory in other brain regions.

PMID- 1981092
TI  - Behavioural physiology of serotonergic and steroid-like anxiolytics as antistress
      drugs.
AB  - Pharmacological studies are useful tools to understand the neurobiological basis
      of behavioural and physiological stress mechanisms. Ipsapirone, a 5-HT1A
      autoreceptor agonist is a representative of novel anxiolytics without the
      disadvantages of benzodiazepam-like drugs. Behavioural, physiological and
      neuroendocrine studies in the rat are reviewed which were aimed to investigate
      the antistress properties of ipsapirone during reexposure to various conditioned
      emotional stress situations. It is demonstrated that in certain situations,
      probably due to a stress-induced sensitisation of postsynaptic 5-HT1A receptors,
      anxiolytic doses of the drug may show prostress (anxiogenic) behavioural and
      neuroendocrine effects. Furthermore, brain corticosteroid receptors, probably
      interacting with the serotonergic transmission, are involved in
      anxiogenic/prostress processes. In this respect antagonists of the brain
      mineralocorticoid-like (type I) receptors may be important antistress drugs of
      the future.

PMID- 1981094
TI  - [Algodystrophic syndromes. Physiotherapy and rehabilitation].

PMID- 1981093
TI  - [Achievements in endocrinology].

PMID- 1981096
TI  - [A new method for detection of DNA polymorphisms using the polymerase chain
      reaction].

PMID- 1981095
TI  - [Psychoses in epilepsy].
AB  - The heterogenous psychoses in epilepsies, caused by well known conditions, are
      not rare but associated with regularly a few of seizure-types not with the nature
      and development of attacks. Polar transitional ranks and converging courses of
      schizophrenic (accentuated) syndromes in epilepsies and idiopathic schizophrenias
      are rather frequent. Also (sub-)acute schizophrenic psychoses are corresponding
      to the complete palette of first and second rank symptoms (K. Schneider) of
      idiopathic schizophrenias. After manifestations of epilepsy these syndromes can
      appear at any time. It is given a profile of risks. Progressive avoidance of a.
      phenylaceturea, b. mixtures of antiepileptics did not put an end to psychotic
      syndromes: Long-term therapies with 1. Polytherapy, 2. Primidone and Phenytoin
      (dosedependant) as well as 3. Ethosuximide (-monotherapy) cause a disorder of
      feed back mechanisms, especially a disturbed regulation of vigilance and sleeping
      waking-cycle and their psychological correlates. Carbamazepine and Sodium
      Valproate are, plasma-level-controlled of preventive antipsychotic effect.
      Selected neuroleptics of rather slight epileptogenic potency are of going down
      importance. Benzodiazepines are required mostly in prepsychotic syndromes,
      Lithium compounds in selected cases. There is no more alternative seizures or
      psychosis.

PMID- 1981097
TI  - Nephrotoxicity: mechanisms, early diagnosis and therapeutic management. 4th
      International Nephrotoxicity Symposium. Surrey, England, July 1989.

PMID- 1981098
TI  - Effects on renal hemodynamics and tubular function of the contrast medium iohexol
      in renal patients.
AB  - Renal function was assessed in 20 (11 female and 9 male, age 21-76 years, mean
      53) renal patients with a creatinine clearance 25-145 ml/min, mean 95, to
      evaluate the effects of iohexol, a non-ionic low-osmolar contrast medium.
      Intravenous urography was performed in 16 patients and computed body tomography
      in 4, using a dose of iohexol ranged between 0.6-3.3 (mean 1.17) g/kg b.w.
      Different parameters of renal function were determined in the week preceding and
      1, 3 and 5 days after the administration of iohexol. The principal renal effect
      of iohexol was an increase of urinary alanine aminopeptidase, gamma
      glutamyltransferase, lactate dehydrogenase, alkaline phosphatase and N-acetyl
      beta-D-glucosaminidase. The maximum increase of enzymuria was observed on day 1
      after the administration of iohexol. In most cases enzymes returned to base-line
      values within 3 days. No relevant variation of renal hemodynamics (glomerular
      filtration rate and effective renal plasma flow) was observed after iohexol. In
      conclusion, iohexol can increase of urinary enzymes, but the effect is rapidly
      reversible and is not accompanied by a clinically significant impairment of renal
      hemodynamics.

PMID- 1981100
TI  - [Beta-blocker therapy for chronic heart failure in patients with dilated
      cardiomyopathy].

PMID- 1981099
TI  - Liver enzyme abnormalities in subacute thyroiditis.
AB  - In a retrospective study of liver function tests in subacute thyroiditis, 13 out
      of 22 patients with the disease demonstrated an elevation of alkaline phosphatase
      level. Less prevalent abnormalities were elevations in gamma-glutamyl
      transpeptidase (5 pts), alanine (4 pts) and aspartate (3 pts) aminotransferase
      activities. These enzyme alterations were not correlated with thyroid hormone
      levels, concomitant diseases, drugs or alcoholic intake, and normalized in six
      patients followed until recovery. A benign, short-lived and subclinical hepatic
      involvement is common in subacute thyroiditis.

PMID- 1981101
TI  - Unusual proliferation of the pancreatic endocrine cells in adults, suggestive of
      islet cell metaplasia.
AB  - We present two adult autopsy cases with malignancy, in which unusual
      proliferation of the pancreatic endocrine cells was observed. Histopathological
      examination revealed extensive proliferation of the pancreatic endocrine cells
      throughout the pancreata in both cases. The islets of the pancreas were enlarged
      with irregular contours. An admixture of the islet cells, acinar cells and
      ductular epithelial cells was also observed. Immunohistochemically, these islets
      were composed of the endocrine cells of various types, i.e. A-, B-, D- and PP
      cells, and they showed a predominance of PP-cells. Clinically, endocrine
      hyperfunction of the pancreas was not detected in either cases. Although this
      histological change may be described as endocrine cell hyperplasia or dysplasia,
      the close connection of the islet cells, acinar cells and ductular epithelial
      cells might rather suggest metaplastic change of the acinar or ductular cells
      into the islet cells under unknown stimuli.

PMID- 1981102
TI  - Electroencephalographic effects of modafinil, an alpha-1-adrenergic
      psychostimulant, on the sleep of rhesus monkeys.
AB  - An electroencephalographic (EEG) study on the rhesus monkey, primate model of
      human sleep, showed the significant wakening effect of a new psychostimulant,
      Modafinil. The first experiment, with single administration of three increasing
      doses of Modafinil (3, 6, and 12 mg/kg), was to determine the efficient threshold
      dose; the second experiment, with repeated administration of 22.5 mg/kg during 4
      days, was to determine whether continuous wakefulness could be obtained without
      apparent behavioral disorders. Results of the first experiment showed a wakening
      effect above 6 mg/kg, but 12 mg/kg induced a sharp wakening effect with a
      significant decrease in all sleep stages. The second experiment induced important
      insomnia in all subjects for 4 days and 4 nights. No behavioral disorder was
      observed. Modafinil has a wakening effect at the dose of 6 mg/kg in rhesus
      monkeys and induces quasicontinuous wakefulness for 4 total days and nights with
      daily administration of 22.5 mg/kg, with no behavioral disorders. Modafinil
      should therefore find interesting applications in sleep disorder treatments.

PMID- 1981103
TI  - Pharmacology of drugs for conscious sedation.
AB  - In endoscopic monitoring and treatment of gastrointestinal disease, it is
      important that patients will accept repeated examination. They are less likely to
      do so if the procedure is remembered as distressing or uncomfortable, as is
      likely when it is performed under topical anaesthesia alone. The aim of conscious
      sedation is a lightly sedated patient, who is awake, cooperative on demand,
      amnesic, and free from anxiety and fear. Various drugs in low doses can be used
      to meet these criteria. Among these are phenothiazines, butyrophenones,
      barbiturate and non-barbiturate hypnotics, benzodiazepines, and the hypno
      analgesic, ketamine. As benzodiazepines offer both sedative and profound amnesic
      and anxiolytic effects, these drugs are used for conscious sedation worldwide.
      Diazepam has been the 'gold standard' of sedation, but the more modern
      benzodiazepines, particularly midazolam, are now more commonly used. In general,
      benzodiazepines demonstrate a broad therapeutic range. In accordance with dose,
      however, sedative drugs may induce side-effects, such as drowsiness, lowering of
      blood pressure, and respiratory depression. In addition, some may induce more
      wide-ranging side-effects, such as histamine liberation and anaphylactic
      reactions, thrombophlebitis, and pain on injection. They may have severe drug
      interactions when used in combination with local anaesthetics, hypnotics and
      opioids. In older patients, lower doses are necessary for sedation. Sedative
      drugs should be administered slowly, to avoid haemodynamic and respiratory side
      effects.

PMID- 1981104
TI  - Which agent and how to deliver it? A review of benzodiazepine sedation and its
      reversal in endoscopy.
AB  - Amnesia, relaxation, and cooperation, not anaesthesia, should be the clinical end
      points when using intravenous sedative drugs for endoscopic procedures. Diazepam
      has now been replaced by midazolam as the first-choice sedative agent to achieve
      these effects. Midazolam, when used in correct doses, is more suited to endoscopy
      than diazepam because of its shorter elimination half-life, larger volume of
      distribution, and faster total body clearance. Midazolam is also clinically
      superior, as it achieves amnesia in twice as many patients and at lighter levels
      of sedation than with diazepam. The routine use of opioids in combination with
      benzodiazepines is to be avoided, as it increases the likelihood of adverse
      cardiopulmonary events. The availability of the specific benzodiazepine
      antagonist, flumazenil, is not an excuse for the administration of excessive
      doses of benzodiazepines. Flumazenil is an essential emergency drug when
      benzodiazepine-induced sedation is used. Reversing single-dose benzodiazepine
      induced sedation after outpatient endoscopy enables earlier accurate retention of
      information and earlier discharge and may have significant cost-benefit
      implications.

PMID- 1981105
TI  - Antimicrobial prophylaxis. Proceedings of a symposium. Oslo, May 4-5, 1990.

PMID- 1981106
TI  - Response to "Effects of caffeine on behavior of schizophrenic inpatients".
AB  - This article addresses itself to the apparent conflict between those reports
      indicating that caffeine affects schizophrenic behavior and the present study
      which failed to show substantial behavior or medication changes with caffeine. It
      is suggested that there are important subgroups of schizophrenic patients who are
      unusually sensitive to caffeine's apparent psychotogenic actions as reported in
      case reports and data on violence and destruction. It is also suggested that
      there are subgroups of schizophrenia which seem to require increased medication
      doses to "cover" caffeine effects.

PMID- 1981107
TI  - Schizophrenia: a subcortical neurotransmitter imbalance syndrome?
AB  - Recent animal experiments suggest that glutamate plays a fundamental role in the
      control of psychomotor activity. This is illustrated by the finding that even in
      the virtually complete absence of dopamine, a marked behavioral activation is
      produced in mice following suppression of glutamatergic neurotransmission. This
      article discusses the possibility that a deficient activity within the cortico
      striatal glutamatergic pathway is an important pathophysiological component in
      some cases of schizophrenia and that glutamatergic agonists may prove beneficial
      in this disorder. In a broader perspective, schizophrenia may be looked upon as a
      syndrome induced by a neurotransmitter imbalance in a feedback-regulated system,
      where dopamine and glutamate play a crucial role in controlling arousal and the
      processing of signals from the outer world to the cerebral cortex via the
      thalamus.

PMID- 1981108
TI  - Neuroleptics: effects on neuropsychological function in chronic schizophrenic
      patients.
AB  - We have reviewed the literature from the 1950's to the present on the effects of
      neuroleptics on perceptual and neuropsychological function in chronic
      schizophrenic patients. In contrast to previous reviews, we have delineated the
      acute and chronic effects of neuroleptics on individual cognitive and motor tasks
      by drug, dose, and length of administration. To date, studies have shown that
      acute administration of neuroleptics impairs performance on some, but not all,
      tasks requiring vigilance and attention, and on some tasks requiring motor
      behavior. Chronic administration of neuroleptics, however, improves performance
      on some tasks requiring sustained attention and visuomotor problem-solving skills
      depending on dose and length of administration. Moreover, there is consistent
      evidence to suggest that chronic administration of neuroleptics in this patient
      population does not impair neuropsychological function independent of motor
      function. These findings have direct implications regarding the risk/benefit
      ratio and legal ramifications for the use of neuroleptics in chronic
      schizophrenic patients.

PMID- 1981109
TI  - [Symposium: Venous thromboembolism in orthopedic surgery: A risk to be prevented.
      10 September 1990, Montreal, Canada].

PMID- 1981110
TI  - Complex osteocutaneous injuries--timing of reconstruction. A report of 3 cases.
AB  - Twenty-seven patients with osseous trauma and soft-tissue loss were subjected to
      a treatment protocol aimed at obtaining definitive wound coverage within 10 days
      of injury. Reconstructive procedures included 19 successful microvascular tissue
      transfers as well as 8 pedicle flaps. The rate of serious complications was 8%,
      and patient morbidity was significantly reduced compared with a previous regimen
      of late reconstruction. An outline of the protocol is presented and technical
      points, which might enhance results, are discussed.

PMID- 1981111
TI  - Dopamine neuron ontogeny: electrophysiological studies.
AB  - The ontogeny of nigrostriatal dopamine (NSDA) neurons was examined with single
      unit extracellular electrophysiological methods. The physiological and
      pharmacological characteristics of 2-, 4-, and 5-week-old rat pup NSDA neurons
      were compared with those of adults (8-10 weeks old). Although the basal discharge
      rate, conduction velocity, and firing pattern of NSDA neurons from 4- and 5-week
      old rats were similar to adults, the 2-week-old-rats differed significantly in
      all three of these physiological characteristics. The conduction velocity and
      basal discharge rate were found to be significantly lower in the 2-week-old pups
      relative to adults. In addition, there were significantly fewer bursting NSDA
      neurons in 2-week-olds than there were in adults. Two and 4-week-olds exhibited
      significantly lower sensitivity to cumulative intravenous doses of apomorphine.
      In contrast, the sensitivity to cumulative intravenous doses of quinpirole was
      found to be similar across all age groups. It is evident that the pharmacological
      and physiological properties of NSDA neurons are in a dynamic state of flux
      during postnatal development. These electrophysiological findings are discussed
      in the context of the perinatal development of midbrain DA systems.

PMID- 1981112
TI  - Positron emission tomography (PET) studies of dopaminergic/cholinergic
      interactions in the baboon brain.
AB  - Interactions between the dopaminergic D2 receptor system and the muscarinic
      cholinergic system in the corpus striatum of adult female baboons (Papio anubis)
      were examined using positron emission tomography (PET) combined with [18F]N
      methylspiroperidol [( 18F]NMSP) (to probe D2 receptor availability) and [N-11C
      methyl]benztropine (to probe muscarinic cholinergic receptor availability).
      Pretreatment with benztropine, a long-lasting anticholinergic drug, bilaterally
      reduced the incorporation of radioactivity in the corpus striatum but did not
      alter that observed in the cerebellum or the rate of metabolism of [18F]NMSP in
      plasma. Pretreatment with unlabelled NMSP, a potent dopaminergic antagonist,
      reduced the incorporation of [N-11C-methyl]benztropine in all brain regions, with
      the greatest effect being in the corpus striatum greater than cortex greater than
      thalamus greater than cerebellum, but did not alter the rate of metabolism of the
      labelled benztropine in the plasma. These reductions in the incorporation of
      either [18F]NMSP or [N-11C-methyl]benztropine exceeded the normal variation in
      tracer incorporation in repeated studies in the same animal. This study
      demonstrates that PET can be used as a tool for investigating interactions
      between neurochemically different yet functionally linked neurotransmitters
      systems in vivo and provides insight into the consequences of multiple
      pharmacologic administration.

PMID- 1981113
TI  - Gamma-glutamyl transferase in neonatal non-hemolytic indirect hyperbilirubinemia.
AB  - Serum gamma-glutamyl transferase (GGT) activities were determined on the third
      day of life in healthy controls (n:15) and in infants with non-hemolytic
      hyperbilirubinemia (n:16). GGT activities were 39.6 +/- 28.4 units/ml and 46.6 +/
      26.7 units/ml, respectively. There was no statistical difference between both
      groups (p greater than 0.05).

PMID- 1981114
TI  - [Value of retinal fluorescence angiography in Takayasu disease].

PMID- 1981115
TI  - [Epidemiologic characteristics of hemorrhagic fever with renal syndrome in a
      disease reservoir near Foca].

PMID- 1981116
TI  - Effect of omeprazole on serum gastrin levels: influence of age and sex.
AB  - Serum gastrin levels were determined in 120 consecutive patients (43 females, 77
      males) with peptic disease 24 h post dose after 4 weeks continuous omeprazole (40
      mg daily) treatment. Serum gastrin levels were elevated in 33 (28%) but exceeded
      the twice normal range in only 6 patients (5%). Age and sex did not influence the
      magnitude of gastrin levels. Gastrin increments induced by omeprazole compared to
      pretreatment with H2-blockers in 60 cases were similar in both males (42 +/- 10
      pg/ml) and females (44 +/- 9 pg/ml). It is concluded that the magnitude of
      gastrin increases observed during omeprazole therapy are small and independent of
      age and sex.

PMID- 1981117
TI  - [Does omeprazole damage genes?].

PMID- 1981118
TI  - [The use of H-1 antihistamine preparations in neurodermatitis patients].
AB  - Correlations between clinical variants of neurodermatitis course and patients'
      lymphocyte sensitivity to histamine are analyzed. The atopic form is associated
      with high lymphocyte sensitivity to histamine. Administration of H-1
      antihistaminic agents to these patients is not always justified. Antihistaminic
      drugs should be prescribed to neurodermatitis patients with due consideration for
      the individual sensitivity of patient's lymphocytes to histamine.

PMID- 1981119
TI  - [Stimulant therapy of hyperkinetic syndrome in childhood and adolescence].

PMID- 1981120
TI  - [Etiological, determinant and systemic mechanisms of disorders of the central
      nervous system].
AB  - New concepts are related of the etiology and pathogenesis of a number of nervous
      disorders, resting on the theory of the generator, determinant and systemic
      mechanisms. It has been shown that after brain damage the development of the
      pathological process in this organ is put into effect by the endogenous
      mechanisms common to the altered nervous system itself. These mechanisms include
      origination of the generators of pathologically enhanced excitation, pathological
      determinants and pathological systems. Formation of the indicated pathological
      structural and functional formations comprises typical processes brought about,
      respectively, at the levels of interneuronal, systemic and ++intersystemic
      relations. These processes eventuate in formation of the pathological systems of
      the brain.

PMID- 1981121
TI  - Venous thromboembolism--managing the risk. Proceedings of a symposium. Berlin,
      October 6-7, 1989.

PMID- 1981122
TI  - Aging and stress-induced changes in choline and glutamate uptake in hippocampus
      and septum of two rat strains differing in longevity and reactivity to stressors.
AB  - Stress induced changes in neurochemical indices of neurotransmission are more
      pronounced in the septohippocampal cholinergic system of Wistar Kyoto rats, which
      are behaviorally more reactive to stressors and have a shorter life span, than in
      Brown Norway rats. Moreover, pronounced degeneration of septohippocampal
      cholinergic neurons occurs earlier in life in Wistar Kyoto rats. In the present
      study the high affinity synaptosomal uptakes of choline and glutamate were used
      as indices for cholinergic and glutamatergic systems respectively. Following 2 hr
      of mild restrain stress increases in both uptake systems were observed in all
      regions examined (hippocampus, septum and frontal cortex). The stress-induced
      increases were generally similar in young (3 months) and aged (20 months) rats of
      both strains. The noted exception was that choline uptake levels, which were
      reduced in the hippocampus of unhandled aged WKY rats, remained unchanged after
      stress. The results confirm the involvement of the septohippocampal cholinergic
      system in the response to acute stress and extend the findings to include the
      hippocamposeptal glutamatergic system activation as well. It is suggested that in
      spite of neuronal degeneration during aging, these responses to stress can be
      maintained by compensatory efforts of neurons that remain intact.

PMID- 1981123
TI  - Proceedings of the Fourth International Conference on Immunobiology and
      Prophylaxis of Human Herpesvirus Infections. October 4-6, 1989, Fukuoka, Japan.

PMID- 1981124
TI  - Addictive behaviors and benzodiazepines: 2. Are there differences between
      benzodiazepines in potential for physical dependence and abuse liability?
AB  - This paper examines data on the question of possible differences between
      benzodiazepines in abuse liability and potential for causing physical dependence.
      The data on potential for causing physical dependence indicates that all
      benzodiazepines cause physical dependence and there is little evidence for
      substantial differences between them in this respect. The evidence for
      substantive differences between benzodiazepines with respect to abuse liability
      is reviewed: problems with methodology and with definitions make problematic the
      assertion of some authors that there are clinically meaningful differences in
      abuse liability. There is general agreement that all benzodiazepines have at
      least some abuse liability.

PMID- 1981125
TI  - [Sipple's syndrome: a case report].
AB  - A 41-year-old woman was hospitalized for evaluation of diabetes mellitus and
      hypertension. The hormonal and radiological examinations revealed that she had
      pheochromocytoma of bilateral adrenal gland and medullary carcinoma of thyroid
      gland. Therefore, she was diagnosed as having Sipple's syndrome. She had no
      definite familial history, but her two sisters, already dead, had been strongly
      suspected of having had pheochromocytoma. First, bilateral adrenalectomy was
      performed and secondly, total thyroidectomy, excision of parathyroid and cervical
      lymph node dissection were performed. Histopathological diagnosis was
      pheochromocytoma of bilateral adrenal gland, medullary carcinoma of thyroid gland
      and chief cell hyperplasia of parathyroid gland. We report a case of Sipple's
      syndrome, which probably is the 88th case in Japan, with the review of the
      previous Japanese literature.

PMID- 1981126
TI  - [Efficacy of combination of Ea-0643 (bunazosin hydrochloride) and bethanechol
      chloride in patients with neurogenic bladder].
AB  - Bethanechol chloride, a cholinergic agent and bunazosin hydrochloride, an alpha
      adrenergic blocking agent were administered orally to 28 patients with neurogenic
      bladder due to peripheral nerve disorders. To compare the effect of the two
      drugs, one of the drugs was initially administered orally for 2 weeks, and then
      both of them were administered for the next 2 weeks. Since there were some
      significant differences in the patient background between the two groups, it was
      difficult to compare the two drugs. However combined use of these drugs resulted
      in both objective and subjective good responses in those patients.

PMID- 1981127
TI  - [Anesthesia in the diagnostic stages of cerebral arteriovenous malformations in
      children under 3 years of age].
AB  - From 1974 through 1989, 36 patients with arteriovenous malformations were treated
      in the neuroradiological unit of the Santobono Children's Hospital, in Naples, 7
      of these patients were younger than 3 years of age. During such a time-span,
      dramatic improvements in diagnostic work-up were jelded by introduction of CT
      scan and MRI; better angiographic techniques, progress in anaesthesia drugs,
      equipment and procedures and more rational surgical modalities. Anaesthesia must
      be tailored in each patient with special consideration of the clinical and
      neurological conditions of the patients as well of the neuroradiological
      procedure, specifically, with minimal side effects on cardiovascular and
      respiratory functions as well on intracranial pressure. The present paper discuss
      of equipment for cardiovascular assistance and drugs to be employed in the
      various steps of the diagnostic work-up of such patients.

PMID- 1981129
TI  - Program and abstracts of the Joint Convention of the 5th International Child
      Neurology Congress and the 3rd Asian and Oceanian Congress of Child Neurology.
      Tokyo, November 4-9, 1990. Abstracts.

PMID- 1981128
TI  - [Peroperative recovery in surgery of arteriovenous malformations in children
      under the age of 3 years].
AB  - From 1974 through 1989, 36 patients with arteriovenous malformations were studied
      in the neurosurgical department of the Santobono Children's Hospital in Naples; 7
      of these patients were younger than three years of age: 5 underwent surgery. The
      remaining 2 patients presented, respectively, an aneurysm of the vein of Galen
      and an arteriovenous malformation of the brain stem. Improvements in surgical and
      anesthesiological techniques allow to treat lesions considered as not amenable to
      surgery until recent years, with minimal occurrence of preoperative and
      postoperative complication and a significant amelioration of prognosis.

PMID- 1981130
TI  - [The effect of anesthesia on the neurohumoral regulation system and water
      electrolyte balance during aortocoronary bypass].
AB  - Two methods of multicomponent general anesthesia distinct in the analgetic agent
      used to ensure analgesia have been compared. In group I (6 patients) analgesia
      was ensured by fentanyl at a dose of 10 micrograms/(kg/min), in group II (7
      patients) it was ensured by pyritramide (dipidolor) at a dose of 2 mg/kg for the
      whole operative period. The study has shown that during aortocoronary bypass
      surgery in patients with ischemic heart disease analgesia is better ensured by
      pyritramide than by fentanyl administration. The latter technique of analgesia
      should be improved, as the current modification causes almost twice as great
      stress-reaction as the one employing pyritramide.

PMID- 1981131
TI  - Determination of some beta-blockers as dabsyl derivatives by HPLC.
AB  - A HPLC method has been developed that permits the sensitive determination of beta
      adrenergic blocking drugs, including acebutolol, metoprolol, oxprenolol,
      pindolol, and propranolol. These compounds were converted to their chromophoric
      dabsyl derivatives and were separated by a reversed phase chromatographic column
      (mu-Bondapak C18) with methanol-water (75:25) as isocratic mobile phase. The
      derivatives were detected by a variable wavelength detector operating at 430 nm.
      The method was applied to commercial pharmaceutical preparations and the results
      were statistically compared with those obtained by official methods using t- and
      F-tests.

PMID- 1981132
TI  - Papers presented at the International Conference on Structure and Functions of
      Biomembranes. Calcutta, India, November 28-December 2, 1989. Proceedings.

PMID- 1981133
TI  - [DNA polymorphisms and haplotypes in the apoAI-CIII gene region and coronary
      heart disease].
AB  - Polymorphisms and haplotypes identified by DNA Restriction Fragment Length
      Polymorphisms in the apoAI-CIII gene region were investigated both in 33 Chinese
      patients with coronary heart disease and 50 unrelated healthy subjects, using
      genomic DNA hybridization analysis with a 1.0 kb fragment of the human apoAI gene
      cDNA. The frequencies of the S2 and M2 alleles were 0.167 and 0.22 in healthy
      subjects, 0.11 and 0.24 in patients respectively. There were no differences in
      the frequencies of the S2 and M2 alleles between patients and healthy subjects.
      Since none of the subjects had the genotypes, S1S2M1M1, S2S2M1M2 and S2S2M1M1,
      all of the S2 alleles were considered to be associated with the M2 alleles at
      least in Chinese population. The alleles identified by the apoCIII Sst-I and
      apoAI Msp-I polymorphisms are in linkage disequilibrium. The individuals with the
      haplotype S1-M2 were significantly increased in patients compared with the ones
      in healthy subjects (26% versus 4.6%; chi 2 = 6.91, d.f = 1, P less than 0.01).
      The results of the present study suggest that both the apoCIII Sst-I and apoAI
      Msp-I polymorphisms may be a useful genetic marker for the analysis of apoAI-CIII
      gene complex and the haplotype S1-M2 may be a useful linkage marker for the
      putative atherogenic gene in Chinese.

PMID- 1981134
TI  - Clinical evaluation of serum N-acetyl-beta-D-glucosaminidase as a liver function
      test.
AB  - Serum N-acetyl-beta-D-glucosaminidase has been shown to be a sensitive indicator
      of liver function. The enzyme activity in serum from patients with different
      forms of hepatic disease was found to be elevated. A comparison is also made with
      routine liver parameters. The frequencies of pathological serum levels of the
      routine measurements made are in relatively good agreement with earlier reports.

PMID- 1981135
TI  - Modulation of the renin-aldosterone system by iodotyrosines as tyrosine
      hydroxylase inhibitors.
AB  - This study shows that MIT and DIT stimulate aldosterone secretion. This may be
      due to their tyrosine hydroxylase inhibitory property. Dopamine abolishes the
      stimulation. Prolonged MIT administration enhances the stimulation of aldosterone
      secretion and can cause hypokalemia. Volume expansion reverses the
      hyperaldosteronism. PRA and blood pressure do not change, even after prolonged
      MIT intake.

PMID- 1981136
TI  - [Sulfasalazine in rheumatology].
AB  - Sulphasalazine (SLZ) has proved to be a drug effective in inducing clinical
      improvement or remission in chronic inflammatory rheumatic diseases (other than
      inflammatory bowel diseases) such as rheumatoid arthritis (RA) and some
      seronegative spondyloarthropathies, in a fashion similar to that of long-acting,
      second-line drugs in RA. Several clinical studies agree upon the efficacy of the
      compound employed at a dose of 2-3 g/day and upon the incidence of side effects,
      which appear to be equivalent to or lower than those related to traditional
      disease-modifying drugs employed in RA. The following points should be clarified
      and developed with regard to the use of SLZ in chronic rheumatic diseases: main
      mechanism(s) of action, improvement of therapeutic strategy (i.e.: combined
      treatments, maintenance therapy), prevention and control of main side effects,
      and its preferential use or limits in the management of a larger number of
      inflammatory rheumatic diseases.

PMID- 1981137
TI  - An evaluation of the alpha-adrenoceptor antagonism produced by SK&F 86466 in
      healthy normotensive males.
AB  - SK&F 86466 is a novel, potent alpha-adrenoceptor antagonist which, in animal
      experiments, is reported to show a high selectivity for alpha 2-adrenoceptors at
      both pre- and post-junctional sites. The effects of two intravenous doses of 80
      and 200 micrograms kg-1 of SK&F 86466 were assessed in a placebo-controlled,
      double-blind, randomised study in eight young, healthy, normotensive males. Two
      indices of alpha-adrenoceptor activity were investigated: i) Pressor
      responsiveness to the relatively selective alpha 1-adrenoceptor agonist
      phenylephrine and to the preferential alpha 2-adrenoceptor agonist alpha
      methylnoradrenaline. ii) Circulating levels of noradrenaline. SK&F 86466 at a
      dose of 200 micrograms kg-1 produced rightward shifts of the pressor dose
      response curves to both agonists: a 1.4 fold shift for phenylephrine (P = 0.023)
      and a 1.6 fold shift for alpha-methylnoradrenaline (P = 0.051). Erect plasma
      noradrenaline sampled at 105 min into the infusion was significantly increased
      from 2.9 to 5.0 nmol l-1 by SK&F 86466 200 micrograms kg-1 (P = 0.002). The
      change in the phenylephrine responses indicates post-junctional alpha 1
      adrenoceptor blockade and the rise in noradrenaline is consistent with pre
      junctional alpha 2-adrenoceptor antagonist activity. Overall the results of this
      study suggest that SK&F 86466, at a dose of 200 micrograms kg-1, causes both
      alpha 1- and alpha 2-adrenoceptor antagonism in human subjects.

PMID- 1981138
TI  - [Study of the APUD cells of the gastric mucosa].
AB  - The results of an histochemical and microscopic study of the APUD cells carried
      on gastric biopsies are reported. Endocrine cell hyperplasia, microscopically
      detected, was particularly evident in atrophic gastritis (type A chronic
      gastritis) and adenomas. The presence of the APUD cells confirmed by
      electronmicroscopy, which revealed granules of 200 NM with a central nucleus and
      a membrane-separating electron-lucent ring, gives a further contribution to the
      hypothesis of a possible association between endocrine cell hyperplasia and
      intestinal metaplasia.

PMID- 1981139
TI  - [Role of surgery in the therapy of peptic ulcer after arrival of H2-blocking
      drugs].
AB  - This retrospective study was undertaken to determine if the advent of H2-blockers
      has altered the surgical treatment and the outcome of patients with peptic ulcer
      disease. The records of patients undergoing surgery for peptic ulcer disease at
      Montecchio Maggiore Hospital, Vicenza (Italy), from 1968 to 1977 (group A) and
      from 1979 to 1989 (group B) were reviewed. Data recorded included, ulcer
      location, surgical procedures (emergency or elective), indications for emergency
      surgery (perforation, bleeding). Statistical analysis was performed by means of
      the chi-square test. From 1968 to 1989, 15.810 surgical operations were
      performed: the indication was peptic ulcer disease in 398 cases (2.51%). The
      percentage of surgical operations performed for peptic ulcer was 3.54% in group A
      and 1.55% in group B. A marked decline in surgery for peptic ulcer was noted in
      group B, concerning both elective and emergency surgery; surgical interventions
      strongly decreased for both duodenal and gastric ulcer. This study demonstrates
      that H2-blockers have definitely altered the surgical treatment for peptic ulcer
      disease.

PMID- 1981140
TI  - [Echographic study of cryptorchidism].
AB  - The authors, after a nosologic review of cryptorchidism, illustrate their
      positive diagnostic experience with ultrasound. Limits as well as clinical
      advantages, in relation to the diagnosis and follow-up, are also described.

PMID- 1981141
TI  - Influence of triiodothyronine on the polypeptide composition of the intestinal
      brush border membrane during amphibian metamorphosis.
AB  - Brush border fragments (BBF) were isolated from homogenates of intestinal
      epithelium prepared from four groups of tadpoles: premetamorphic larvae,
      thyrostatic larvae, spontaneously metamorphosed larvae, and triiodothyronine (T3)
      induced froglets. Isolation was accomplished by a combination of both Ca2+
      precipitation and differential centrifugation methods. These preparations were
      routinely enriched seven- to-eleven-fold for the two amphibian brush border
      marker enzymes, gamma-glutamyltransferase and maltase. Comparison by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) with silver
      staining revealed the presence of a polypeptide of Mr 27,000 only after
      spontaneous and T3-induced metamorphosis. One-dimensional SDS-PAGE together with
      lectin staining showed six strongly concanavalin A reactive polypeptides (Mr
      52,000, 57,000, 65,000, 80,000, 130,000 and 150,000) in both preparations
      examined. Immunoblot analyses allowed us to detect in both preparations the
      presence of villin (Mr 105,000), a cytoskeletal component of microvilli. Two
      dimensional isoelectric focusing IEF/SDS-PAGE together with silver staining
      showed the polypeptides of Mr 41,500, 43,000, 60,500 and 101,000 to be specific
      components of the primary intestinal epithelium brush border. In contrast six
      polypeptides of Mr 27,000, 52,000, 58,000, 59,000 and 95,000 were only detected
      in intestinal BBF after spontaneous and T3-induced metamorphosis. Their presence
      is under the control of the thyroid hormone. The results provide new insight
      regarding the subcellular localization of polypeptides whose synthesis changes
      during spontaneous (Figiel et al., 1987) and T3-induced metamorphosis (Figiel et
      al., 1989).

PMID- 1981142
TI  - The Xenopus laevis Hox 2.1 homeodomain protein is expressed in a narrow band of
      the hindbrain.
AB  - The expression pattern of the Xenopus homeodomain protein Hox 2.1 during
      development was determined using an affinity-purified antibody directed against a
      carboxyterminal peptide. Nuclear staining was detected in a very narrow band of
      the hindbrain. This pattern was compared to that of the previously described
      Xenopus gene XIHbox 1 in serial sections and found to be more anterior than the
      XIHbox 1 long protein expression but overlapping with that of the short protein.
      Xenopus Hox 2.1 protein expression is restricted to a much narrower antero
      posterior band than that reported for mouse Hox 2.1 RNA expression by in situ
      hybridization.

PMID- 1981143
TI  - The presence of c-erbB-2 gene product-related protein in culture medium
      conditioned by breast cancer cell line SK-BR-3.
AB  - The Mr 185,000 glycoprotein encoded by human c-erbB-2/neu/HER2 gene, termed c
      erbB-2 gene product, shows a close structural similarity with epidermal growth
      factor receptor and is now regarded to be a growth factor receptor for an as yet
      unidentified ligand. Abundant c-erbB-2 mRNA was demonstrated by Northern blot
      studies in the human breast cancer cell line SK-BR-3. Cellular radiolabeling
      experiments followed by immunoprecipitation with three different anti-c-erbB-2
      gene product antibodies, recognizing extracellular domain, kinase domain, and
      carboxyl-terminal portion, respectively, demonstrated the production of a large
      amount of c-erbB-2 gene product which had the capacity to be phosphorylated.
      Immunization of mice with concentrated culture medium conditioned by SK-BR-3
      cells always generated antibodies against c-erbB-2 gene product, demonstrating
      that this culture medium contained substance(s) immunologically indistinguishable
      from c-erbB-2 gene product. This observation was supported by the successful
      development of a monoclonal antibody against c-erbB-2 gene product, GFD-OA-p185
      1, by immunizing mice with this culture medium. The biochemical nature of the
      substance(s) present in the culture medium was further characterized. When the
      culture medium conditioned by [35S]cysteine-labeled SK-BR-3 cells was
      immunoprecipitated by three different anti-c-erbB-2 gene product antibodies, only
      the antibody recognizing extracellular domain precipitated the [35S]-labeled
      protein with a molecular weight of 110,000, namely p110. The newly developed
      monoclonal antibody also immunoprecipitated this protein.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1981144
TI  - Preferential retention of paternal alleles in human retinoblastoma: evidence for
      genomic imprinting.
AB  - The origins of the initial mutations in sporadic retinoblastoma were explored
      using polymorphic markers from chromosome 13q. The paternal chromosome was
      maintained in 3 of 3 informative bilateral tumors which had undergone reduction
      to homozygosity for regions of this chromosome. The paternal chromosome was
      maintained in 7 of 8 informative unilateral tumors which likewise demonstrated a
      reduction of homozygosity. These data are in contrast to previously published
      studies of chromosome retention in unilateral retinoblastoma [Dryja, T. P.,
      Mukai, S., Petersen, R., Rapaport, J. M., Walton, D., and Yandel, D. W. Nature
      (Lond.), 339: 556-558, 1989; Zhu, Z., Dunn, J. M., Phillips, R. A., Goddard, A.
      D., Paton, K. E., Becker, A., and Gallie, B. L. Nature (Lond.), 340: 312-313,
      1989] and provide the first evidence that genomic imprinting may play a role in
      this disease.

PMID- 1981145
TI  - Transforming growth factor-alpha expression is enhanced in human mammary
      epithelial cells transformed by an activated c-Ha-ras protooncogene but not by
      the c-neu protooncogene, and overexpression of the transforming growth factor
      alpha complementary DNA leads to transformation.
AB  - MCF-10A cells are a spontaneously immortalized normal human mammary epithelial
      cell line. MCF-10A cells were transfected with two expression vector plasmids
      containing either a human point-mutated c-Ha-ras protooncogene or the rat c-neu
      protooncogene. c-Ha-ras-transfected MCF-10A cells grow as colonies in soft agar,
      exhibit a 3- to 4-fold increase in their growth rate in serum-free medium, and
      show a reduced mitogenic response to exogenous epidermal growth factor (EGF) or
      transforming growth factor-alpha (TGF alpha) as compared to MCF-10A cells. c-Ha
      ras-transfected MCF-10A cells express a 4- to 8-fold increase in TGF alpha mRNA
      levels and secrete 4- to 6-fold more TGF alpha protein as compared to MCF-10A
      cells. Addition of either an anti-TGF alpha neutralizing monoclonal antibody or
      an anti-EGF receptor blocking monoclonal antibody to the Ha-ras-transformed MCF
      10A cells produces a 50 to 80% inhibition of colony formation of these cells in
      soft agar. c-neu-transfected MCF-10A cells grown in soft agar and exhibit an
      increase in their growth rate in serum-free medium at a level comparable to that
      observed in Ha-ras-transformed MCF-10A cells. Addition of an anti-c-erbB-2
      monoclonal antibody inhibits the anchorage-independent growth of these cells in
      soft agar. However, c-neu-transformed MCF-10A cells show no increase in TGF alpha
      secretion and no change in their responsiveness to exogenous EGF or TGF alpha. A
      recombinant retroviral vector containing the human TGF alpha gene was also
      introduced into MCF-10A cells. TGF alpha-infected MCF-10A cells secrete 15- to 20
      fold more TGF alpha protein than MCF-10A cells, form colonies in soft agar,
      exhibit an enhanced growth rate in serum-free medium, and show a decreased
      mitogenic response to exogenous EGF or TGF alpha at a level equivalent to Ha-ras
      transformed MCF-10A cells. Growth of TGF alpha-infected MCF-10A cells in soft
      agar is completely inhibited by anti-TGF alpha neutralizing or anti-EGF receptor
      blocking monoclonal antibodies. These results suggest that TGF alpha is an
      intermediary in the transformation of human mammary epithelial cells by an
      activated c-Ha-ras gene, but not by the c-neu gene, and demonstrate that
      overexpression of this growth factor is able to transform immortalized human
      mammary epithelial cells which also express a sufficient complement of functional
      EGF receptors.

PMID- 1981146
TI  - Somatostatin and prosomatostatin in the retina of the rat: an
      immunohistochemical, in-situ hybridization, and chromatographic study.
AB  - Specific antisera, raised in rabbits, against somatostatin 1-14, somatostatin 1
      28, the fragment 1-12 of somatostatin 1-28, and prosomatostatin 20-36 were used
      for immunohistochemistry and gel filtration of the rat retina. With all antisera,
      immunoreactive perikarya could be located in the inner nuclear and ganglion cell
      layers. In the inner nuclear layer, amacrine cells with processes extending
      predominantly into the first sublayer of the inner plexiform layer were observed.
      Some processes extended also to the ganglion cell layer. In addition,
      somatostatin-immunoreactive interplexiform cells were present in the inner
      nuclear layer. In the ganglion cell layer, perikarya were found located in the
      midperiphery and in the far periphery of the retina. The neurons located in the
      midperiphery of the retina possessed a round perikaryon from which processes
      could be followed going into the inner plexiform layer, where they dichotomized
      in the third and first sublayers. The perikarya in the far periphery of the
      retina near the ora serrata exhibited an ovoid-shaped cell body from which
      processes extended horizontally in a bipolar manner in the layer itself. By use
      of an [35S]-labeled antisense oligonucleotide probe, in situ hybridization of the
      rat retina showed the presence of perikarya in the inner nuclear layer and
      ganglion cell layer containing mRNA encoding for prosomatostatin. Gel filtration
      of the retinal extracts followed by radioimmunoassay showed the presence of
      somatostatin 1-14, the fragment 1-12 of somatostatin 1-28, and prosomatostatin 1
      64. However, somatostatin 1-28 was not detected. The results obtained in this
      study verify the presence of somatostatin 1-14 in the rat retina located in
      perikarya and processes in the inner nuclear and ganglion cell layers. The
      positive in-situ hybridization signals show that the intraneuronal somatostatin
      immunoreactivity is due to synthesis of the peptide and not uptake in the
      neurons. The presence of the somatostatin propeptide and fragments of this
      propeptide, in both intraretinal perikarya and fibers, indicate a
      posttranslational modification of this neuropeptide in the perikarya and the
      processes as well.

PMID- 1981147
TI  - Freshly isolated Thy-1+ dendritic epidermal cells express T cell receptor gamma
      delta-CD3.
AB  - Within murine epidermis exists a population of Thy-1+ DEC which express membrane
      Thy-1 antigen, but lack CD8 or CD4 antigen. We examined freshly obtained non
      cultured Thy-1+ DEC both by immunofluorescence and by biochemical techniques to
      identify the protein products of the T cell receptor (TCR) and the associated CD3
      complex on these cells. Virtually all of the Thy-1+ DEC are brightly positive in
      CD3 expression with immunofluorescence using the monoclonal antibody 145-2C11. By
      immunoprecipitation, using this same antibody and polyclonal anti-TCR-gamma
      antibody, the only TCR heterodimer detected on the freshly isolated Thy-1+ DEC is
      the gamma delta heterodimer. These findings suggest that in the phenotype and TCR
      expression, Thy-1+ DEC are analogous to CD8-, CD4- early fetal thymocytes.

PMID- 1981148
TI  - Activation of tat-defective human immunodeficiency virus by ultraviolet light.
AB  - Ultraviolet light (UV) is known to cause activation of gene expression from the
      human immunodeficiency virus type 1 (HIV-1) promoter. To address the question of
      whether tat-defective HIV-1 provirus could be rescued by UV irradiation we
      examined its effect on HeLa cells containing integrated proviruses with tat
      mutations. Exposure of these cells to an optimal dose of UV resulted in the
      production of infectious viruses. The degree of UV activation and reversion to
      infectious virus appeared to depend on the nature of the original tat mutation.
      Two of the mutants required cocultivation with tat-expressing cells to fully
      generate replication competent viruses, while a third mutant required only
      cocultivation with H9 cells. Sequencing of cDNA from cells infected with this
      last mutant demonstrated that the parental mutant sequence was retained and that
      genotypic revertants to the wild-type as well as new mutant sequences were
      generated. These results suggest that tat-defective HIV-1 provirus can be
      activated by UV and can subsequently revert to wild-type virus. This study raises
      the possibility that UV exposure of immune cells in the skin plays a role in the
      activation of defective HIV-1 in vivo.

PMID- 1981149
TI  - Depressive syndromes in schizophrenic patients after discharge from hospital. ANI
      Study Group Berlin, Dusseldorf, Gottingen, Munich.
AB  - A total of 364 schizophrenic outpatients who were stabilized for 3 months on
      continuous neuroleptic therapy after discharge from the hospital were rated
      according to three different scales for depressive syndromes (Brief Psychiatric
      Rating Scale anxious depression factor, AMDP/depression, and the self-rating PD-S
      depression scale). Between 19.5% and 27.5% of the patients were rated as
      depressed, or 35.7%-42.8%, when mild depressive syndromes were included. There
      were low, but significant correlations between demographic or life-event data and
      depression scores on the self-rating scale, whereas fewer correlations were found
      on the observer ratings. No associations were found between social adjustment and
      depression. Moderate correlations were found between measures of the apathetic
      syndrome and depression ratings, while observer ratings showed higher
      correlations than the self-rating. High depression scores, especially in the
      observer ratings, correlated with scales for global psychopathological assessment
      (CGI, GAS). There were significant correlations between extrapyramidal rigidity
      and observer rating depression scores, whereas the total amount of neuroleptics
      given had no influence. These results are interpreted on the basis of hypotheses
      about depressive syndromes in schizophrenia.

PMID- 1981151
TI  - Drug trials and heterogeneity in schizophrenia: the mean is not the end.

PMID- 1981152
TI  - MRI in tardive dyskinesia: shortened left caudate T2.
AB  - High-resolution magnetic resonance imaging of the brain was performed on 18 male
      schizophrenic patients, 14 with a cumulative exposure to neuroleptics of more
      than 1 year and 4 with less than 3 months of exposure. Calculated T2 relaxation
      time values were obtained for the basal ganglia. Patients with tardive dyskinesia
      (n = 9) had significantly shortened left caudate T2 relaxation times when
      compared to patients without tardive dyskinesia (n = 5). The group of four
      patients with fewer than 3 months' exposure to neuroleptics demonstrated a
      significantly greater variability of their left caudate T2 values. T2 relaxation
      time shortening may be related to iron levels in the basal ganglia and may be of
      predictive value in evaluating risk of tardive dyskinesia.

PMID- 1981153
TI  - Xylazine enhances porcine myometrial contractility in vitro: possible involvement
      of alpha 2-adrenoceptors and Ca2+ channels.
AB  - The effects of xylazine on porcine myometrial contractility were studied in vitro
      using uterine strips to determine the alpha 2-adrenergic influences during the
      diestrous stage of the estrous cycle. Xylazine (10(-8)-10(-5) M) caused a dose
      dependent increase in the amplitude of myometrial contractility. The alpha 2
      adrenoceptor antagonists idazoxan and yohimbine (10(-8)-10(-6) M) blocked the
      effects of xylazine in a dose-dependent manner. Yohimbine was approximately 10
      times more potent than idazoxan in this regard. In contrast, an alpha 1
      adrenoceptor antagonist prazosin (10(-7) and 10(-6) M) did not block the xylazine
      induced increase in myometrial contractility, but a higher dose of prazosin (10(
      5) M) did reduce the effects of xylazine. When the porcine uterine strips were
      pretreated with Ca2(+)-free Tyrod's solution or verapamil, a Ca2+ channel
      blocker, the effects of xylazine on myometrial contractility were completely
      abolished, whereas those of carbachol were only moderately reduced. The results
      suggest that the xylazine-induced myometrial contractility is mediated by alpha 2
      adrenoceptors and that this effect is mediated, at least in part, by Ca2+
      channels, whereas the effect of carbachol is attributed to an increase in both
      Ca2+ entry and release of Ca2+ from intracellular pools.

PMID- 1981154
TI  - The proceeding of the International Symposium on Liquid Chromatography and
      Enzymes. 9-11 April 1990, London, UK.

PMID- 1981150
TI  - Glutamate in the mammalian CNS.
AB  - The excitatory amino acid glutamate plays an important role in the mammalian CNS.
      Studies conducted from 1940 to 1950 suggested that oral administration of
      glutamate could have a beneficial effect on normal and retardate intelligence.
      The neurotoxic nature of glutamate resulting in excitotoxic lesions (neuronal
      death) is thought possibly to underlie several neurological diseases including
      Huntington's disease, status epilepticus. Alzheimer's dementia and
      olivopontocerebellar atrophy. This neurodegenerative effect of glutamate also
      appears to regulate the formation, modulation and degeneration of brain
      cytoarchitecture during normal development and adult plasticity, by altering
      neuronal outgrowth and synaptogenesis. In addition to its function as a
      neurotransmitter in several regions of the CNS, glutamate seems to be
      specifically implicated in the memory process. Long-term potentiation (LTP) and
      long-term depression (LTD), two forms of synaptic plasticity associated with
      learning and memory, both involve glutamate receptors. Studies with antagonists
      of glutamate receptors reveal a highly selective dependency of LTP and LTD on the
      N-methyl-D-aspartate and quisqualate receptors respectively. The therapeutic
      value of glutamate receptor antagonists is being actively investigated. The most
      promising results have been obtained in epilepsy and to some extent in ischaemia
      and stroke. The major drawback remains the inability of antagonists to permeate
      the blood-brain barrier when administered systemically. Efforts should be
      directed towards finding antagonists that are lipid soluble and able to cross the
      blood-brain barrier and to find precursors that would yield the antagonist
      intracerebrally.

PMID- 1981155
TI  - Serum levels of methadone in maintenance clients who persist in illicit drug use.
AB  - This study examined pharmacological factors contributing to persisting drug abuse
      by methadone maintenance clients. Three groups of clients, drawn from one
      treatment programme, were studied: persistent heroin users, persistent
      benzodiazepine users, and control subjects who were not using illicit drugs in
      addition to methadone. Persistent abusers mostly had high trough serum methadone
      levels, and their ongoing drug use appears to reflect a preference for a
      different drug effect rather than inadequate methadone dose. Several clients did
      have the expectation that methadone should prevent them from using other drugs;
      such expectations may diminish the effectiveness of treatment.

PMID- 1981156
TI  - The patterns of neurotransmitter and neuropeptide co-occurrence among striatal
      projection neurons: conclusions based on recent findings.
AB  - The neurotransmitter organization of striatal projection neurons appears to be
      less complex than once thought. Only 4 major evolutionarily conserved populations
      appear to be present. The neurons of two of these populations contain SP, DYN and
      GABA, with one of these two populations consisting of striatonigral projection
      neurons and the other of striatopallidal projection neurons. The two additional
      major populations of striatal projection neurons consist of striatopallidal and
      striato-nigral neurons that both contain both ENK and GABA. Although these
      conclusions greatly simplify the understanding of the organization of striatal
      projection neurons by suggesting that only a few major populations are present,
      these conclusions complicate understanding of neurotransmission between these
      neurons and their target areas by suggesting that each neuron utilizes multiple
      neuroactive substances to influence target neurons. Further studies will
      therefore be required to explore the mechanisms of neurotransmission by which
      striatal neurons communicate with their target areas.

PMID- 1981157
TI  - The effect of neuroleptics on cognitive and psychomotor function.
AB  - There has been great variability and inconsistency in the reported effects of
      neuroleptic drugs on cognitive and psychomotor function in both patients and
      normal controls. Experimental design rather than any particular cognitive or
      psychomotor test appears to have determined the sensitivity of detection of
      neuroleptic drug effects. In general, sedative phenothiazines have been found to
      depress psychomotor function and sustained attention, but higher cognitive
      functions are relatively unaffected. In the majority of studies of schizophrenic
      patients, both cognitive function and attention improve with neuroleptic
      treatment, in parallel with clinical recovery. Negative symptoms are not
      increased and usually show slight improvement with neuroleptic treatment.
      Controls are more sensitive than schizophrenic patients to neuroleptic drug
      induced impairments. Tolerance has been seen in patients but has not been
      demonstrated in normal volunteers. The way in which neuroleptics produce their
      beneficial effects in patients remains unknown. Three main hypotheses to replace
      early arousal theories are proposed: normalisation of attention, facilitated
      indirectly by suppression of 'released' limbic dopamine hyperactivity;
      normalisation of asymmetrical temporohippocampal function; or direct improvement
      of attentional processing. Studies of the effects of new antipsychotic drugs with
      selective actions and the development of more reliable and selective tests of
      psychomotor and cognitive functions are required.

PMID- 1981158
TI  - Extrapyramidal signs, primitive reflexes and frontal lobe function in senile
      dementia of the Alzheimer type.
AB  - Of 146 elderly subjects suffering from Alzheimer-type dementia, 44% were found to
      have significant extrapyramidal signs. Although extrapyramidal signs were more
      common in those who had taken neuroleptic drugs in the preceding six months, 22
      subjects (15%) who were drug free also had extrapyramidal signs. Scores for
      cognitive function and for 'frontal lobe' signs (verbal fluency, evidence of
      perseveration, and primitive reflexes) were found to correlate well with scores
      for extrapyramidal signs, suggesting that they reflect changes in a common
      substratum. It is tentatively suggested that this might be an abnormality in the
      dopamine system.

PMID- 1981159
TI  - Benzodiazepine withdrawal.

PMID- 1981160
TI  - Cholera toxin-B subunit blocks excitatory effects of opioids on sensory neuron
      action potentials indicating that GM1 ganglioside may regulate Gs-linked opioid
      receptor functions.
AB  - In a previous study, we demonstrated that cholera toxin-A subunit, as well as the
      whole toxin, selectively blocks opioid-induced prolongation of the Ca2+ component
      of the action potential duration (APD) in dorsal root ganglion (DRG) neurons,
      indicating mediation of this excitatory effect by Gs-linked opioid receptors. The
      present study shows that pretreatment of DRG neurons with the B subunit of
      cholera toxin (1-10 ng/ml; greater than 15 min) can also block mu/delta and kappa
      opioid-induced APD prolongation, but not shortening. Since the B subunit binds
      selectively to GM1 ganglioside located on the cell surface, these results suggest
      that this ganglioside may regulate Gs-linked excitatory opioid receptor functions
      in DRG neurons. Possible contamination of purified B subunit preparations of
      cholera toxin with traces of the more potent A subunit was eliminated by heating
      the stock solution to 56 degrees C for 20 min. Exposure of DRG neurons to an
      affinity-purified anti-GM1 antiserum also blocked opioid-induced APD
      prolongation, providing further evidence that GM1 ganglioside may play an
      essential role in excitatory opioid modulation of the action potential of these
      cells. The blockade by cholera toxin-B subunit and anti-GM1 antibodies of opioid
      induced APD prolongation is best accounted for by the following hypothesis: CTX-B
      interferes with an endogenous GM1 ganglioside component of the excitatory, but
      not inhibitory, opioid receptor complex on DRG neurons that may allosterically
      regulate coupling of the receptors via Gs to adenylate cyclase/cyclic adenosine
      monophosphate-dependent ionic conductances.

PMID- 1981161
TI  - Increase of tyrosine hydroxylase-like immunoreactive neurons in the nucleus
      accumbens and the olfactory bulb in the rat with the lesion in the ventral
      tegmental area of the midbrain.
AB  - A small number of neurons in the nucleus accumbens of the rat showed tyrosine
      hydroxylase-like immunoreactivity (TH-LI). These TH-LI neurons had medium-sized
      cell bodies with several spiny dendrites. When a lesion was produced in the
      ventral tegmental area of the midbrain by injecting 6-hydroxydopamine, TH-LI
      neurons in the nucleus accumbens, as well as those in the olfactory bulb, were
      increased in number on the side ipsilateral to the lesion. The results indicated
      that expression of TH might be enhanced in some neurons deprived of dopaminergic
      afferent fibers.

PMID- 1981162
TI  - The evolution of nigrostriatal neurochemical changes in the MPTP-treated squirrel
      monkey.
AB  - The MPTP-treated monkey has become an important model for the study of
      Parkinson's disease. However, studies on the acute evolution of the neurotoxic
      effects of MPTP in primates are lacking. In the present study, 17 squirrel
      monkeys were given a single subcutaneous injection of MPTP (2.5 mg/kg). The
      behavioral effects and the concentrations of dopamine (DA), dihydroxyphenylacetic
      acid and homovanillic acid were determined in caudate, putamen and substantia
      nigra 1, 3, 5 (n = 3/time point) and 10 days (n = 6) after drug administration.
      Two animals were studied neuropathologically 8 and 9 days after MPTP. Profound
      parkinsonism was evident in all animals after 1 day and neuropathological
      examination revealed severe nerve cell destruction in the substantia nigra.
      Surprisingly, although 50-75% reductions in nigral DA were observed 1 and 3 days
      after MPTP, caudate DA was not reduced and putaminal DA was increased at these
      time points. The temporal sequence of these events differs markedly from that
      which occurs in the MPTP-treated mouse and suggests that, in the monkey, nigral
      cell bodies may represent an important initial site of MPTP-induced damage. Five
      and 10 days after MPTP, nigral DA depletions remained greater than 60% of control
      and striatal DA was reduced 50-85%. At these time points, the putamen was always
      more affected than the caudate. This interregional pattern of striatal DA
      deficits is similar to that seen in idiopathic Parkinson's disease.

PMID- 1981163
TI  - Intraventricular injection of neurotensin reduces dopamine D2 agonist binding in
      rat forebrain and intermediate lobe of the pituitary gland. Relationship to serum
      hormone levels and nerve terminal coexistence.
AB  - In order to investigate neurotensin-dopamine receptor interactions in vivo, the
      effects of intraventricular injection of neurotensin were analyzed on S(-)[N
      propyl-3H(N)]propylnorapomorphine [( 3H]NPA) binding in cryostat sections of the
      forebrain, hypothalamus and pituitary gland, and on serum levels of prolactin,
      luteinizing hormone and corticosterone in the male rat. The relationship of
      modulation of [3H]NPA binding with neurotensin-dopamine coexistence in nerve
      terminals was analyzed by investigating coexistence of neurotensin and tyrosine
      hydroxylase (TH) immunoreactive nerve terminals in various brain areas, using a
      double immunohistofluorescence procedure. Intraventricular injections of
      neurotensin (0.03-3 nmol, 30 min) reduced dose-dependently specific [3H]NPA
      binding (0.25 nM) in the caudate-putamen (-38 +/- 4%), nucleus accumbens (-42 +/-
      5%), tuberculum olfactorium (-52 +/- 7%) and in the intermediate lobe of the
      pituitary gland (-17 +/- 2%). Coexistence of neurotensin and TH was demonstrated
      in nerve terminals in the prefrontal, cingulate, piriform and entorhinal cortex
      and in the cortical and deep nuclei of the amygdaloid cortex. It was not possible
      to demonstrate coexistence in the caudate-putamen, nucleus accumbens, tuberculum
      olfactorium and median eminence, in view of the high density of dopamine nerve
      terminals present in relation to the few visualized neurotensin terminals. Nor
      could coexistence be demonstrated in the few remaining TH-positive nerve
      terminals following unilateral 6-hydroxydopamine lesions (8 micrograms per 4
      microliters; one week) in spite of increased numbers of neurotensin-containing
      cell bodies and terminals in the ipsilateral dorsomedial caudate. Neurotensin
      injection markedly decreased serum prolactin levels and increased serum
      corticosterone levels by about 60%, whereas serum levels of luteinizing hormone
      were unaffected. The present study indicates that central dopamine D2 receptors
      may be regulated by neurotensin in vivo and that the neurotensin involved most
      likely is released from nerve terminals not containing dopamine, since fibers
      showing coexistence were only found in prefrontal and limbic cortical areas.

PMID- 1981164
TI  - Excitatory amino acid involvement in retinal degeneration.
AB  - Amino acid analysis using high-performance liquid chromatography demonstrated
      high levels of the excitatory amino acids, aspartate and glutamate, in the
      retinas of congenitally blind chicks at the time of photoreceptor degeneration.
      Concentrations of aspartate were about 2 times higher in blind chicks than in
      retinas of age-matched sighted chicks that were carriers for the genetic defect.
      Glutamate levels were similar in blind chicks and carriers at 1 day of age, but
      doubled and tripled sighted chick values at 1 week and 2 weeks of age in blind
      chick retinas. Light microscopic immunocytochemistry using antibodies that
      recognize aspartate and glutamate revealed increased levels of these two amino
      acids specifically in the photoreceptor layer of blind chicks. This report is the
      first to demonstrate high endogenous levels of excitatory amino acids associated
      with a hereditary degeneration of photoreceptor cells.

PMID- 1981165
TI  - GABAB receptors play a major role in paired-pulse facilitation in area CA1 of the
      rat hippocampus.
AB  - Extracellular recordings of field potentials in area CA1 of the rat hippocampal
      slice have been used to investigate paired-pulse facilitation. Field potentials
      were evoked by maximal stimulation of the Schaffer collateral/commissural fibres.
      The height of the population spike (PS) in stratum pyramidale (str. pyr.) and the
      area under the field excitatory postsynaptic potential (EPSP) following the PS in
      the stratum radiatum (str. rad.) were quantified. These values were used to
      describe the time course of paired-pulse facilitation. Facilitation of the PS was
      maximal 50 ms after the conditioning pulse and was present over a period of about
      500 ms. However, facilitation of the late area (LA) of the field EPSP was maximal
      afer 125 ms and had an overall duration of 1-2 s. The N-methyl-D-aspartate (NMDA)
      receptor antagonist, 2-amino-5-phosphonovaleric acid (APV), had no effect on
      paired-pulse facilitation of either the LA or the PS. The gamma-aminobutyric acid
      B (GABAB) agonist baclofen increased facilitation of the PS. This was mainly due
      to a reduction of the unconditioned response. Facilitation of the LA was reduced
      by both baclofen and the GABAB antagonist, 2-OH-saclofen. Baclofen increased the
      LA of the unconditioned response, while this was unaffected by 2-OH-saclofen. The
      LA of facilitated responses was decreased by 2-OH-saclofen while the effect of
      baclofen on these responses was more complex. Baclofen reduced the LA of
      maximally facilitated responses, while the LA of slightly facilitated responses
      was increased. The results show that different mechanisms are involved in the
      facilitation of the LA and the PS. Furthermore, activation of GABAB receptors
      makes a large contribution to paired-pulse facilitation of the field EPSP. It is
      also suggested that recording of extracellular fields in str. rad. in response to
      paired-pulse stimulation provides a simple electrophysiological model for testing
      the effect of agents which act at the GABAB receptor.

PMID- 1981166
TI  - MK-801 blocks dynorphin A (1-13)-induced loss of the tail-flick reflex in the
      rat.
AB  - Dynorphin A (1-13) administered intrathecally to rats results in a dose-dependent
      loss of the tail-flick reflex. This effect is mediated, at least in part, by N
      methyl-D-aspartate receptors. We examined the influence of pretreatment or post
      treatment with MK-801 on this behavioral response. MK-801 administered i.p. 30
      min prior to dynorphin provided dose-dependent protection against loss of the
      tail-flick reflex with an ED50 of 0.06 mg/kg. MK-801 administered after dynorphin
      had a dose- and time-dependent protective action. The dose of 0.06 mg/kg
      protected 63% of the animals from loss of the tail-flick reflex when injected 15
      min after dynorphin. In contrast, 3 mg/kg did not protect animals when injected
      15 min after dynorphin, but did protect 50% of the animals when injected 30 min
      post-dynorphin. Although we cannot exclude other effects mediated by MK-801,
      these data support our previous findings that dynorphin-induced loss of the tail
      flick reflex involves the N-methyl-D-aspartate-receptor complex and support the
      contention that the process(es) initiated by dynorphin injection proceed rapidly
      (minutes rather than hours).

PMID- 1981167
TI  - Alpha-adrenergic receptor agonists, but not antagonists, alter the tail-flick
      latency when microinjected into the rostral ventromedial medulla of the lightly
      anesthetized rat.
AB  - The present experiments, part of an ongoing study designed to characterise the
      role of norepinephrine (NE) in regulating the activity of putative nociceptive
      modulatory neurons in the rostral ventromedial medulla (RVM), assessed the
      effects of alpha-adrenergic receptor-selective agents on the nociceptive
      threshold (as measured by the tail-flick withdrawal response on noxious heat).
      These microinjection studies were carried out in the barbiturate-anesthetized
      rat, a preparation which is favourable for acute neurophysiological studies. The
      data obtained demonstrate that, as observed by others in the awake animal,
      activation of alpha 2-adrenergic receptors in the RVM produces hypoalgesia.
      However, unlike in the awake animal, when antagonists selective for either the
      alpha 1- or alpha 2-adrenergic receptor are microinjected alone into the RVM
      there is no change in the nociceptive threshold. These data suggest that the
      alpha 2-adrenergic receptor has a postsynaptic location and that barbiturate
      anaesthesia suppresses a tonically active or noxious stimulus-activated
      noradrenergic input to the RVM that is present in the awake animal.

PMID- 1981168
TI  - Culture of mature hippocampus slices for 4 days in a newly developed medium:
      preservation of transmitter release and leucine incorporation into protein.
AB  - A procedure and a medium for sustaining mature hippocampus slices in vitro for 4
      days are described. The ionic composition of the medium, in which the slices were
      incubated for 1 h of recovery following preparation, strongly affected their
      ability, 4 days later, to take up and to release D-[3H]aspartate and [14C]GABA. A
      medium deficient in Na+ and Ca2+ proved best for recovery of the fresh slices
      prior to transfer to culture medium. The newly developed CSF-like culture medium
      was the best among several media tested in maintaining the potential of the
      slices for uptake and for induced release of D-[3H]aspartate and [14C]GABA.
      Glutamine, present in most culture media, appeared to be particularly toxic.
      Relative to fresh slices, the slices after 4 days in culture maintained 118% and
      97% of the uptake of D-[3H]aspartate and of [14C]GABA respectively. K(+)-induced
      release of D-[3H]aspartate and of [14C]GABA was 104% and 82% of the respective
      values in fresh slices. Under the optimal culture conditions worked out, the
      slices also regained a considerable capacity for incorporation of labelled
      leucine into protein, which was low in fresh slices.

PMID- 1981169
TI  - Effects of pertussis toxin on caudate neuron electrophysiology: studies with
      dopamine D1 and D2 agonists.
AB  - The selective D1 and D2-agonists SKF-38393 and N-0437 respectively, were tested
      in caudate pretreated with PT. A paired recording paradigm was used where the
      contralateral untreated caudate served as a control. Micropipettes were used to
      locally apply SKF-38393 and N-0437 onto neurons in both control and PT-pretreated
      caudate. A significant attenuation of the responses to the D2 agonist were
      observed after PT administration. Only 1 out of 12 cells tested on the PT side
      demonstrated any response to locally applied N-0437, whereas 90% of the neurons
      responded to the drug on the control side. Neurons from both the PT-pretreated
      and control caudates responded to locally applied SKF-38393. In addition to the
      specific D1 and D2 receptor agonists, DA and the indirect dopamine agonist PCP
      were tested for changes in responsiveness. Dopamine was equally efficacious at
      both control and PT-pretreated caudate neurons, which suggest that dopamine
      locally applied from the micropipette can interact with the unperturbed D1
      receptors in the PT-pretreated caudate. On the other hand, the response to PCP
      was significantly attenuated after PT administration, which suggest that
      endogenously released DA preferentially interacts with the D2 receptor subtype.
      Taken together these data suggest an important role for the D2 receptor in the
      physiology of dopamine responsiveness in the caudate nucleus.

PMID- 1981170
TI  - Hemispheric asymmetry in behavioral response to D1 and D2 receptor agonists in
      the nucleus accumbens.
AB  - The present study examined the locomotor response of rats to unilateral
      injections of the mixed D1/D2 agonist apomorphine, the D2 agonist quinpirole, and
      the D1 agonist SKF 38393 into the left or right nucleus accumbens (NA) of male
      Sprague-Dawley rats. There were 2 main findings. First, unilateral (left or
      right) injections of apomorphine, quinpirole, or SKF 38393 all provoked locomotor
      hyperactivity. The second and more important finding was that, at specific
      dosages, apomorphine and SKF 38393 injections into the right NA produced
      significantly more locomotor hyperactivity than identical injections into the
      left NA. These findings suggest the presence of asymmetries in the NA which may
      involve quantitative differences in the distribution of D1 and D2 receptors.

PMID- 1981171
TI  - Ontogeny of somatostatin expression in primary cultures of cortical neurons
      parallels that seen in vivo.
AB  - The expression of somatostatin (SS) was followed during the development of rat
      cortical neurons growing in primary cultures. The appearance of SS mRNA is
      delayed in cultures of cortical neurons, where it is not readily detectable prior
      to 5 days in culture. Between 5 and 11 days in vitro, there is a large increase
      in the level of SS mRNA in these cultures. The analysis of SS immunoreactive
      neurons indicates that they represent a significant proportion of the total
      neuronal population in these cultures. The majority of these neurons are bipolar
      or stellate in morphology, although some pyramidal cells are also immunoreactive
      for SS. More neurons are immunoreactive for SS28 than for SS28(1-12).
      Immunoreactivity for SS28(1-12) is primarily localized throughout the entire soma
      and neurites, while SS28 reactivity is mainly perinuclear in location. These
      results indicate that the development of SS neurons in primary cortical culture
      parallels normal cortical SS ontogeny in vivo, suggesting that these cultures
      provide a suitable model for the study of intrinsic neocortical peptidergic
      neurons.

PMID- 1981172
TI  - Dapiprazole, a selective alpha-1 adrenoceptor antagonist, inhibits diuresis but
      not polydipsia produced by amphetamine in rats.
AB  - Chronic amphetamine administration has been found to produce diuresis and
      polydipsia in rats. We have found that dapiprazole acutely suppresses the
      diuretic, but not the ingestive, effects of amphetamine. To see whether diuresis
      is the physiological stimulus driving amphetamine-mediated polydipsia, we
      injected rats daily with d,l-amphetamine and the alpha-1 adrenergic antagonist
      dapiprazole. Throughout 19 days of treatment, dapiprazole completely prevented
      the increased urine output produced by amphetamine, but did not affect the
      development of polydipsia. This finding rules out a renal site of the primary
      action for amphetamine-mediated polydipsia and proposes water and electrolyte
      imbalance produced by chronic amphetamine administration as a model of the
      polydipsia and hyponatremia that develop in some psychotic patients.

PMID- 1981173
TI  - Intrathecal administration of calcitonin gene-related peptide (CGRP) increases
      heart rate and decreases arterial pressure in the urethane anesthetized rat.
AB  - Intrathecal administration of CGRP (2.15-8.60 nmol) to the ninth thoracic
      vertebral segment of the spinal cord in the urethane anesthetized rat provoked an
      increase in heart rate (peak effect of 72 bpm) and a decrease in arterial
      pressure (maximum fall of 15 mmHg). Administration of CGRP to the T2 level (n =
      10) or intravenously (n = 6) produced qualitatively and quantitatively similar
      effects to those observed following administration to the T9 level. The drop in
      pressure resulting from intrathecal administration was unaffected by prior
      intrathecal administration of lidocaine (250 micrograms), systemic administration
      of hexamethonium (5 mg/rat), bilateral vagotomy, or combined bilateral
      vagotomy/hexamethonium treatment. The failure of these manipulations to alter the
      hypotension induced by intrathecal CGRP injection suggests that this effect was
      caused by leakage into the periphery. The cardioacceleration elicited by
      intrathecal CGRP was attenuated by intrathecal lidocaine administration and by
      combined bilateral vagotomy/hexamethonium treatment, but not by either treatment
      alone. These results suggest that CGRP's tachycardic effect is mediated by a
      direct spinal action involving both sympathetic and parasympathetic mechanisms.

PMID- 1981174
TI  - Organization of peptidergic and catecholaminergic efferents from the nucleus of
      the solitary tract to the rat amygdala.
AB  - Previous studies have focused on the role of the central nucleus of the amygdala
      (CeA) in cardiovascular and other amygdaloid functions. The combined retrograde
      tracing/immunohistochemical method was used to test for the presence of
      enkephalin, neurotensin, neuropeptide Y, and catecholamine neurons within the
      nucleus of the solitary tract that send efferents to the CeA. After injections of
      retrograde tracer into the CeA, retrogradely labeled neurons were observed within
      the caudal, medial nucleus of the solitary tract. Most CeA-projecting neurons
      were located ipsilaterally within the medial nucleus of the solitary tract at the
      level of the area postrema. Retrogradely labeled enkephalin- and neurotensin
      immunoreactive neurons were found within the medial nucleus of the solitary tract
      at this level, while retrogradely labeled neuropeptide Y-immunoreactive neurons
      were found within the medial nucleus of the solitary tract rostral to the area
      postrema. About 60-74% of CeA-projecting cells were also immunoreactive for
      tyrosine hydroxylase. Approximately 9% of retrogradely neurons were
      phenylethanolamine-N-methyltransferase immunoreactive. The results provide
      evidence that within the nucleus of the solitary tract, peptidergic CeA
      projecting neurons have a topographic distribution. In addition, noradrenergic
      neurons within the A2 group, rather than adrenergic neurons of the C2 group,
      provide the bulk of catecholaminergic input to the CeA from the nucleus of the
      solitary tract. Cell counts indicate that each of these peptides may be
      colocalized (to varying extents) within catecholamine-producing neurons. Also the
      catecholaminergic and enkephalinergic contribution to the ascending pathway from
      the nucleus of the solitary tract to the CeA distinguishes it neurochemically
      from the descending pathway. Thus, although there are afferent and efferent
      connections between the nucleus of the solitary tract and CeA, their
      peptidergic/neurotransmitter connections are not necessarily reciprocal. Input
      from nucleus of the solitary tract peptidergic and catecholaminergic neurons to
      the CeA may be important in the etiology of a number of pathophysiological
      conditions including hypertension, gastric ulcers, and schizophrenia.

PMID- 1981175
TI  - Tyrosine hydroxylase-positive fibers and neurons in transplanted striatal tissue
      in rats with quinolinic acid lesions of the striatum.
AB  - Using the quinolinic acid (QA) animal model of Huntington's disease (HD) the
      dopaminergic afferent input to intrastriatal striatal grafts was examined. After
      bilateral striatal lesions with QA (15 nmol), 4 microliters of fetal (E17)
      striatal tissue were delivered into the lesioned striata. Twenty-eight weeks
      posttransplantation the tissue was processed for TH immunocytochemistry and
      cresyl violet staining. In addition fetal intact brains (E17) were also processed
      for TH immunocytochemistry and cresyl violet staining. Viable striatal grafts
      were located within the host striatum and in some cases within the lateral
      ventricles. TH-positive fibers were present within the graft and also groups of
      TH-positive cell bodies were seen in some of the grafts. TH immunocytochemistry
      on E17 fetuses revealed several groups of TH-positive neurons one of which was
      placed immediately ventral to the developing striatal ridge. The origin of TH
      positive innervation within the graft is discussed.

PMID- 1981176
TI  - MIF-1 and Tyr-MIF-1 do not alter GABA binding on the GABAA receptor.
AB  - The endogenous brain peptides MIF-1 and Tyr-MIF-1 have been reported to alter
      binding at several sites on the GABAA receptor. To determine whether these
      peptides affect binding at the GABA site, we assessed effects of MIF-1 and Tyr
      MIF-1 on [3H]SR 95531 binding in mouse cortical synaptosomal membranes. Neither
      peptide altered [3H]SR 95531 binding across a wide range of concentrations (10(
      12)-10(-6) M). Scatchard analysis indicated no change in either apparent affinity
      or receptor density at both the high-affinity and low-affinity GABA sites with
      MIF-1 or Tyr-MIF-1, 10(-9) M. Thus, MIF-1 and Tyr-MIF-1 do not affect binding at
      the GABA site on the GABAA receptor.

PMID- 1981177
TI  - Milestones in clinical pharmacology. Psychotropic drugs.

PMID- 1981178
TI  - [New findings in the pathogenesis and diagnosis of disorders of growth and
      development in children including receptor disorders].

PMID- 1981179
TI  - Association of DNA-haplotypes in the human LDL-receptor gene with normal serum
      cholesterol levels.
AB  - For the low density lipoprotein receptor (LDLR), many mutations have been
      characterized which identify this gene as one with an important role in lipid
      metabolism in patients with familial hypercholesterolemia (FH). Genetic
      heterogeneity at this locus raises the possibility that the LDLR may also
      contribute to variation in cholesterol levels in the normocholesterolemic
      population. We have determined genotypes at the LDLR locus using restriction
      fragment length polymorphisms (RFLPs) detected with the enzymes StuI, ApalI,
      PvuII and NcoI in 324 normocholesterolemic individuals from Germany. A
      significant association (p less than 0.01) was detected between the cutting site
      for the PvuII RFLP and lower cholesterol levels, and variation associated with
      this polymorphism explains 3% of the sample variance in cholesterol levels. In
      family studies we have determined four-RFLP haplotypes of 148 independent LDLR
      genes and have observed 9 haplotypes in the population. Three of these haplotypes
      containing the cutting site for PvuII are associated with a reduction in plasma
      LDL-cholesterol levels. Phylogenetic analysis indicates that these three
      haplotypes are related by evolutionary history, and this suggests that a single
      functionally important sequence change in the LDLR explains our observations. Our
      data confirm other reports and strongly suggest that the LDLR locus may be one of
      those genes involved in determining serum cholesterol levels in the normal
      population.

PMID- 1981180
TI  - Exclusion mapping of the Cohen syndrome gene from the Prader-Willi syndrome
      locus.
AB  - Karyotype and DNA analyses using DNA probes were carried out in a family with the
      Cohen syndrome. Two affected brothers had normal chromosomal constitutions. A
      major deletion or duplication of genomic DNA fragments hybridized with the DNA
      probes, pML34 at D15S9 locus and pTD3-21 at D15S10 locus, assigned on 15q11-q12
      was not detected in the patients. In addition, a linkage of the syndrome to D15S9
      and D15S10 loci was not observed in the family. These data suggest that a gene
      for the Cohen syndrome is excluded from the 15q11-q12 region, on which a gene for
      the Prader-Willi syndrome is assigned, and that the Cohen syndrome is distinctly
      different from the Prader-Willi syndrome, although clinical manifestations of the
      Cohen and the Prader-Willi syndromes are very similar.

PMID- 1981181
TI  - Common intragenic and extragenic polymorphisms of blood coagulation factors VIII
      and IX are different in Chinese and Caucasian populations.
AB  - In order to examine the possibilities of carrier detection and prenatal diagnosis
      in hemophilia A and B in the Chinese region of Suzhou, we analyzed four different
      RFLPs within the factor IX gene and two intragenic RFLPs and one extragenic RFLP
      for the factor VIII gene. The results obtained show important differences between
      the Chinese and Caucasian populations. No polymorphism was found within the
      factor IX gene in the Chinese population and the informativity obtained for the
      factor VIII gene was quite different between the two populations for each RFLP
      studied.

PMID- 1981182
TI  - Diagnosis of familial amyloidotic polyneuropathy in France.
AB  - Two cases of familial amyloidotic polyneuropathy (FAP) in a French family are
      reported. Clinical onset was in the fifth and sixth decades with decreased
      sensation in the lower limbs followed by involvement of the upper extremities.
      Motor changes appeared later and evolved to restrict ambulation. Cardiac
      involvement with congestive heart failure and arrhythmias was the cause of death.
      DNA analysis was performed on ten members of this family. Restriction enzyme
      analysis of amplification products of exons 2, 3 and 4 of the prealbumin gene
      were negative for the methionine-30, alanine-60 and serine-84 mutations but
      positive for the tyrosine-77 mutation. The tyrosine-77 prealbumin mutation was
      first described in a family from Illinois with origin in Germany. The discovery
      of the tyrosine-77 gene in the family from Picardy may help to determine the
      origin of this disease and tell us if one mutation has been spread around the
      world, as we suspect, with many kindreds having the methionine-30 gene, or
      whether there have been separate spontaneous mutational events, perhaps a
      peculiarity of this site in the prealbumin gene.

PMID- 1981184
TI  - Artificial intra-abdominal cryptorchidism in young adult rats leads to
      irreversible azoospermia.
AB  - To study reversibility of artificial intra-abdominal cryptorchidism, in four
      groups of 5 rats at 3 months of age vasocystostomies (a microsurgical operation
      anastomosing both sperm ducts into the urine bladder) were carried out. This
      procedure enables sperm output measurements, which was performed by putting the
      animals for 24 h in metabolic cages. Four weeks later 15 of the remaining animals
      were operated again to induce artificial cryptorchidism. In a fourth group, 3
      animals were sham-operated only, leaving the testes in place. Two weeks later in
      the animals of group I cryptorchidism was reversed by an orchiopexy operation; in
      group II orchiopexy was carried out after 4 weeks, in group III after 8 weeks. In
      group IV the animals were sham-operated again. Evaluation of sperm output took
      place for 3 months after orchiopexy. In the 1st week after vasocystostomy the
      animals showed a large variation in sperm output, but 2 weeks later, all animals
      had sperm output between 30-60 x 10(6) of spermatoza/24 h. Immediately after
      cryptorchidism sperm output decreased dramatically, and 2 weeks later all animals
      were azoospermic, except for sham-operated controls. After orchiopexy not one of
      the experimental animals showed any return of spermatozoa. We concluded that
      intra-abdominal cryptorchidism soon leads to irreversible damage to the testes
      resulting in azoospermia.

PMID- 1981183
TI  - Growth hormone and prolactin response to rehydration during exercise: effect of
      water and carbohydrate solutions.
AB  - The effect of progressive rehydration with either water or a carbohydrate
      solution on the plasma growth hormone (GH) and prolactin (PRL) response to
      exercise was examined together with plasma somatostatin. Five subjects underwent
      four 3-h experimental sessions at 36 degrees C in which 25-min exercise periods
      alternated with 5-min rest periods. The sessions were conducted without fluid
      replacement (DH) or under rehydration with either water or isosmotic carbohydrate
      solutions AISO (acid) or NISO (neutral). The fluid was given every 10 min after
      the 1st h of exercise. Plasma GH increased significantly (p less than 0.01) under
      DH after 2 and 3 h of exercise; this increase was prevented by rehydration with
      water, AISO and NISO. Plasma glucose was significantly higher following AISO and
      NISO rehydration compared with DH. This possibly influenced the GH response, but
      there was no difference between plasma glucose levels under DH and water
      rehydration at any time. The solutions tended to attenuate the increase in heart
      rate, rectal temperature and plasma cortisol, suggesting that the lack of GH
      response under rehydration conditions is a result of decreasing physiological
      stress levels. The GH response could not be explained by plasma somatostatin,
      which tended to decline in all sessions. Plasma PRL did not increase in any of
      the sessions, confirming that exercise without rehydration is a more potent
      stimulator of GH than of PRL. It is concluded that progressive rehydration with
      water is sufficient to prevent the exercise-induced increase in plasma GH.

PMID- 1981185
TI  - Ontogeny of locomotor activity and grooming in the young rat: role of dopamine D1
      and D2 receptors.
AB  - Locomotor activity and grooming were assessed in 11- and 17-day-old rat pups
      after treatment with selective dopamine (DA) D-1 and D-2 agonists (SKF 38393 and
      quinpirole, respectively) and antagonists (SCH 23390 and sulpiride,
      respectively). Quinpirole enhanced the locomotor activity of both the 11- and 17
      day-olds, effects antagonized by either SCH 23390 or sulpiride. Drug-induced
      increases in grooming were apparent only after high doses (30.0 mg/kg i.p.) of
      SKF 38393 (11- and 17-day-olds) or when SKF 38393 (15.0 mg/kg i.p.) was given in
      conjunction with sulpiride (11-day-olds). In general, these results suggest that
      challenge with selective DA agonists and antagonists induces patterns of
      responding which are similar to those typically observed in adult rats. Moreover,
      these results indicate that rat pups, like adults, require a functioning DA D-1
      receptor system for the expression of DA D-2-mediated activity.

PMID- 1981186
TI  - Alpha 1-adrenoceptor subtypes and the regulation of peripheral hemodynamics in
      the conscious rat.
AB  - The peripheral hemodynamic effects of SZL-49, a prazosin analog capable of
      selectively inactivating the alpha 1a-adrenoceptor subtype, was evaluated in the
      conscious rat. One hour after SZL-49 administration, total peripheral vascular
      resistance and arterial blood pressure significantly decreased and cardiac output
      and heart rate increased. Twenty-four hours after SZL-49, blood pressure returned
      to control preinjection levels while peripheral resistance remained decreased and
      cardiac output and heart rate were elevated. The phenylephrine dose-response
      curves for mean arterial blood pressure and total peripheral vascular resistance
      were shifted to the right but the maximal responses were not decreased. These
      data show that the alpha 1a receptor plays a role in the tonic maintenance of
      arterial blood pressure. The alpha 1b receptor appears to participate in the
      response to exogenously administered agonists.

PMID- 1981187
TI  - Peripheral analgesia and activation of the nitric oxide-cyclic GMP pathway.
AB  - We have previously described the analgesic effect of dibutyryl cyclic GMP or
      acetylcholine (ACh) injected into rat paws. Since ACh induces nitric oxide (NO)
      release from endothelial cells, we investigated the possible involvement of the
      NO-cyclic GMP pathway in ACh-induced analgesia, using a modification of the
      Randall-Selitto rat paw test. We found that sodium nitroprusside, which releases
      NO non-enzymatically, caused antinociception in the rat paw made hyperalgesic
      with prostaglandin E2. The analgesic effect of sodium nitroprusside and ACh was
      enhanced by intraplantar injection of an inhibitor of cyclic GMP
      phosphodiesterase (MY 5445) and was blocked by a guanylate cyclase inhibitor,
      methylene blue (MB). The analgesia induced by ACh, but not by sodium
      nitroprusside, was blocked by NG-monomethyl-L-arginine (L-NMMA), an inhibitor of
      the formation of NO from L-arginine. L-arginine itself had little or no effect
      upon prostaglandin-induced hyperalgesia but caused significant analgesia in paws
      inflamed with carrageenin. This analgesia was blocked by MB, as well as by L
      NMMA, and was potentiated by MY 5445. These results suggest that ACh-induced
      analgesia was mediated via the release of NO. The results also indicate that the
      guanylate cyclase system is stimulated in the inflammatory reaction. The
      analgesia resulting from activation of this system is possibly overshadowed by
      substances that concomitantly stimulate nociceptor hyperalgesic mechanisms.

PMID- 1981188
TI  - Pharmacological properties of the NMDA receptor involved in somatostatin release
      from cortical neurons.
AB  - Glutamate increases somatostatin release from cultured cerebral cortical neurons,
      presumably through a N-methyl-D-aspartate (NMDA) receptor type. We report here
      that the NMDA response was potentiated by D-serine (10 microM) and that this
      potentiation was blocked by kynurenic acid (4-hydroxyquinoline-2-carboxylic acid;
      KYN). A higher concentration of D-serine (100 microM) reduced the antagonistic
      effect of KYN. Furthermore, the NMDA response exhibited another characteristic
      property of the NMDA receptor: it was decreased by low concentrations of Zn2+ (50
      microM). In contrast, Zn2+ slightly but significantly potentiated the quisqualate
      (QA)- and kainate (KA)-induced responses.

PMID- 1981189
TI  - Azelastine and desmethylazelastine suppress acetylcholine-induced contraction and
      depolarization in human airway smooth muscle.
AB  - We examined the effects of a new anti-asthmatic drug, azelastine, and its
      principal metabolite, desmethylazelastine, on the in vitro electromechanical
      response of human airway smooth muscle during cholinergic stimulation. Membrane
      potential and isometric force were simultaneously measured using an intracellular
      microelectrode and a microforce transducer. Desmethylazelastine significantly
      suppressed acetylcholine-induced depolarization and contraction at 10(-6) M,
      whereas azelastine produced similar results at 10(-4) M, suggesting that the
      metabolite may be the principal compound acting upon the airway smooth muscle
      cell.

PMID- 1981190
TI  - Dopamine D1 receptor stimulation increases striatal acetylcholine release in the
      rat.
AB  - The effect of selective D1 receptor agonists on acetylcholine (ACh) release in
      the striatum was investigated using in vivo microdialysis. Administration of the
      reactive enantiomer, (+)-SKF 38393 (2, 10 mg/kg s.c.), doses which elevate
      grooming and sniffing behaviour, increased ACh release by 40 and 75%,
      respectively. Another D1 receptor agonist CY 204-283 (1 mg/kg s.c.) also produced
      a 75% increase in ACh output. The racemate (+/-)-SFK 38393 (20 mg/kg s.c.)
      increased ACh output by 60% and this was completely blocked by the D1 receptor
      antagonist SCH 23390 (0.3 mg/kg s.c.). In contrast, administration of the D2
      receptor antagonist raclopride (1 mg/kg s.c.), 60 min after (+/-)-SKF 38393 (20
      mg/kg s.c.), further increased ACh release. These results suggest that activation
      of D1 receptors increases ACh release in vivo and that D1 and D2 receptors have
      opposing roles in the regulation of striatal ACh release.

PMID- 1981191
TI  - Precise diagnosis of airflow obstruction - does it matter for treatment? The
      assessment of reversibility; what drugs?

PMID- 1981192
TI  - Long-term treatment in asthma and COPD.

PMID- 1981194
TI  - Antianxiety drugs: nonbenzodiazepines.

PMID- 1981193
TI  - Therapeutic implications of a precise diagnosis of airflow obstruction.

PMID- 1981195
TI  - Phenothiazines and tricyclics.

PMID- 1981196
TI  - Androgen regulation of the mRNA encoding a major protein of the mouse vas
      deferens.
AB  - A cDNA encoding the major mouse vas deferens protein (MVDP) has been cloned and
      characterized. Using in situ hybridization we have identified the epithelial
      cells of the vas deferens as the site of synthesis of MVDP mRNA. Northern blot
      analysis suggests that a high level of an mRNA corresponding to the MVDP gene is
      present in the mouse vas deferens whereas the amount of MVDP mRNA in vas deferens
      of other species studied, or in other mouse tissues, even if present, is
      undetectable. Steady-state levels of MVDP mRNA are decreased by approximately 42%
      3 days after castration but a significant hybridization signal is still observed
      even 50 days after castration. Testosterone treatment for 2 weeks is necessary to
      completely reverse the effect of castration. In vitro transcription assays on
      isolated nuclei showed that the hormonal induction of the MVDP gene is achieved
      mainly at transcriptional level.

PMID- 1981197
TI  - Audit and follow-up of chronic benzodiazepine tranquillizer use in one general
      practice.
AB  - A search of the records of one general practice, serving 5282 patients, generated
      a list of 72 patients (1.36%) who had been using a benzodiazepine tranquillizer
      continuously for more than 6 months. These patients were interviewed and asked to
      discontinue the use of these drugs with the help of their general practitioner.
      An individual approach for each patient was agreed between the general
      practitioner and the patient. Patients who initially did not agree to try to stop
      the drug were included in the study. After 1 year, 27 (37.5%) of the patients had
      stopped using the benzodiazepine completely and 24 (33.3%) had reduced their
      previous consumption by more than 50%. This outcome was independent of sex, age,
      drug used, duration of use, whether they were exceeding the original dose of the
      drug and attendance at a consultant psychiatric clinic. It was significantly more
      likely that the patient would stop taking the drug if they originally wished to
      do so, but several of those who initially did not want to try to stop were able
      to do this. The excess number of consultations for the patients in the study for
      the year of the study compared with the year before the study only constituted
      0.35% of the total number of consultations in the practice. The results were
      better than expected and the exercise was felt to be worthwhile, particularly as
      the increase in workload was very small.

PMID- 1981198
TI  - [Gastric acid secretion and histamine H2 receptor antagonists].

PMID- 1981199
TI  - Control of oxidative damage in rheumatoid arthritis by gold(I)-thiolate drugs.
AB  - The roles of anti-arthritic gold(I)-thiolate drugs such as disodium
      aurothiomalate ('Myocrisin') in the modulation or promotion of oxygen radical
      mediated oxidative damage in vivo are reviewed. In particular, the precise
      molecular mechanisms by which these novel second-line agents exert their
      therapeutic effects are discussed in terms of (i) the direct and indirect control
      of enzymes involved in the generation or scavenging of reactive oxygen species
      (ROS) such as superoxide ion, hydrogen peroxide and hydroxyl radical, (ii) the
      protection of proteins and relevant enzyme systems against attack by ROS and
      (iii) their direct involvement in the production (at appropriate 'target' sites)
      or scavenging of ROS in vivo. In addition, the role of the orally-effective
      gold(I)-phosphine complex auranofin in the control of oxidative damage in
      rheumatoid arthritis is also discussed.

PMID- 1981200
TI  - [Adverse drug effects in bronchial asthma].

PMID- 1981201
TI  - Eighteenth congress of the Czechoslovak Society for Microbiology of the
      Czechoslovak Academy of Sciences. Plzen (Czechoslovakia) July 11-13, 1989.
      Abstracts.

PMID- 1981202
TI  - Effect of CRL 41034 on the adrenergic neuroeffector interaction in the canine
      saphenous vein.
AB  - Experiments were designed to determine the effect of CRL 41034, a buflomedil
      analogue, on the adrenergic responsiveness of canine veins. Rings of saphenous
      vein (without endothelium) were suspended for isometric tension recording in
      modified Krebs-Ringer bicarbonate solution at 37 degrees C. CRL 41034 produced a
      concentration-dependent inhibition of the contractions evoked by the alpha
      adrenergic agonists norepinephrine, phenylephrine and UK 14304 which was
      insensitive to the blockade of neuronal uptake by cocaine. CRL 41034 was more
      potent in inhibiting the concentration-dependent contractions evoked by UK 14304
      than those by phenylephrine and the antagonism it caused against the response to
      UK 14304 fulfilled the criteria for competitivity. CRL 41034, at 10(-5) M
      significantly depressed, and at 10(-4) M abolished the contractions induced by
      electrical stimulation of the adrenergic nerves and those evoked by the indirect
      sympathomimetic amine tyramine. Strips of canine saphenous vein were superfused
      after incubation with [3H] norepinephrine. During sympathetic nerve activation,
      CRL 41304 increased the stimulation-evoked overflow of [3H] norepinephrine and 3
      methoxy-4-dihydroxyphenylglycol; in the presence of rauwolscine the compound only
      increased the stimulation-evoked overflow of 3,4-dihydroxyphenylglycol. These
      experiments suggest that the major vascular effects of CRL 41034 in canine veins
      are blockade of alpha 2-adrenoceptors on vascular smooth muscle, and inhibition
      of prejunctional alpha 2-adrenoceptors on adrenergic nerve endings.

PMID- 1981204
TI  - Beta-blockers and portal hypertension, hemodynamic effects and prevention of
      recurrent gastrointestinal bleeding.
AB  - It has been demonstrated that propranolol might reduce portal pressure by
      reducing cardiac output in patients with cirrhosis and it has thus been
      hypothesized that beta-blockers may be useful as pharmacological treatment for
      portal hypertension (1). Subsequently, further studies have detailed the systemic
      and splanchnic circulatory effects of beta-blockers in patients with portal
      hypertension and in different models of portal hypertension in animals, and
      several controlled studies have been performed. This article reviews the
      hemodynamic effects of beta-blockers in portal hypertension, and reports clinical
      trials on the prevention of recurrent gastrointestinal bleeding.

PMID- 1981203
TI  - Vasoconstrictor therapy in bleeding esophageal varices.

PMID- 1981205
TI  - Prophylactic treatment of esophageal varices before bleeding.
AB  - After years of effort, the treatment of an episode of bleeding from a ruptured
      varix remains unsatisfactory, as does prophylaxis of rebleeding. As a consequence
      it was logical to try to prevent bleeding before the first hemorrhage has
      occurred (primary prophylaxis). Shunt surgery proved to be useful in terms of
      bleeding rate, but side effects and operative risk made this method inapplicable
      for prophylaxis. Endoscopic sclerotherapy was efficient in terms of bleeding
      rate, but doubts about its efficacy in improving survival, together with
      difficulties in performing repeated endoscopies over the long term, have limited
      its use in primary prophylaxis. Beta-blockers have proved useful for preventing
      bleeding and, in some studies, for improving survival. Further studies are still
      necessary to accurately identify the suitable target population, the method of
      follow-up and the duration of treatment. Although some groups have started using
      beta-blockers for prophylaxis before bleeding on a routine basis, others consider
      this treatment only for prospective randomized trials.

PMID- 1981206
TI  - Financing multiple births: a personal point of view.

PMID- 1981207
TI  - The metabolic basis of the fetal alcohol syndrome.

PMID- 1981208
TI  - Preliminary experience with embryo intrafallopian transfer (EIFT).
AB  - Embryo intrafallopian transfer was accomplished in 10 patients. Approximately 48
      hours after oocyte retrieval, the embryonic cleavage stage was evaluated and from
      two to six embryos were transferred to the fallopian tubes at the 2- to 8-cell
      stage using a laparoscopic technique. Five clinical pregnancies resulted; four
      patients have given birth to five healthy babies (one set of twins) and one had a
      miscarriage. These results are encouraging, and we believe that transfer of
      embryos to the fallopian tubes may be an alternative to GIFT or IVF treatment in
      selected groups of patients.

PMID- 1981209
TI  - Opposite responses to the addition of leuprolide acetate to human menopausal
      gonadotropin therapy in two perimenopausal women.
AB  - Leuprolide acetate was used to suppress the endogenous gonadotropins in order to
      prevent premature luteinization in two women under ovulation induction therapy.
      One patient had previously developed premature luteinization with clomiphene
      citrate, but consistently produced only one mature follicle with hMG therapy.
      However, when leuprolide acetate was started prior to hMG during an attempt for
      in vitro fertilization, it failed to stimulate even a mild rise in her serum
      estradiol. The other patient, who was not able to make a mature follicle with hMG
      alone because of premature luteinization, was enabled to make mature follicles
      with leuprolide therapy alone (without hMG). The exact mechanism for these
      totally different responses to leuprolide acetate in two perimenopausal women is
      not known.

PMID- 1981210
TI  - Infertility in a rural area of Jiangsu Province: an epidemiological survey.
AB  - Using a random stratified, multistage, and probability sampling procedure, the
      rate of infertility in the rural area of Jiangsu Province was determined through
      interviews with 2,578 married women of reproductive age. The overall infertility
      rate was 5.0%. A significantly higher rate was found for couples in which the
      husbands were engaged in cotton farming. The study also confirmed the higher
      infertility rate among smokers found in other studies. The infertility rate was
      much higher in the Northern Jiangsu Distinct than in the Southern District,
      suggesting a relationship between infertility and economic/educational
      conditions.

PMID- 1981211
TI  - Gonadotropin releasing hormone (GnRH): mode of action and clinical applications.
      A review.

PMID- 1981212
TI  - Episodic luteinizing hormone release in idiopathic oligospermia.
AB  - The pathophysiology of idiopathic oligospermia (IO) is not fully understood. As
      some males with IO, particularly those with low normal testosterone (T), may
      respond favorably to human menopausal gonadotropin/human chorionic gonadotropin
      (hMG/hCG), aberration in gonadotropin release may be implied in these subjects.
      Therefore, episodic luteinizing hormone (LH) was studied in five males with IO
      and normal T and compared to six normal control males. Blood samples were
      obtained every 20 minutes, commencing at 8 A.M. over a period of six to eight
      hours and assayed for FSH and LH. T was determined at 0, 100, 180, 300, 360, and
      480 minutes. Mean LH of 44.6 +/- 4.8 ng/mL (mean + standard error of the mean) in
      IO was higher than the mean LH of 32.2 + 3.1 ng/mL in the control group (P less
      than .025). Mean FSH of 204.2 +/- 20.3 ng/mL in IO was higher than mean FSH of
      143.1 +/- 22.0 ng/mL in the control group (P less than .05). Mean T of 430 + 56
      ng/dL in IO was comparable to 471 +/- 59.2 in the control group. The frequency of
      LH pulses was similar in both groups. The mean pulse amplitude of LH, 27 +/- 5.5
      ng/mL, in IO was significantly higher than in the control group (15 +/- 2.2
      ng/mL) (P less than .05). Although a central mechanism cannot be excluded, our
      data support a possible abnormality in testicular function in some males with IO.

PMID- 1981213
TI  - Sulfasalazine inhibits the binding of TNF alpha to its receptor.
AB  - Sulfasalazine was found to exhibit a dose-dependent inhibition of human mucosal
      and peripheral blood cytotoxic T-cell function. The drug also inhibited the
      cytotoxic activity of supernatants from anti-CD3-triggered T-cells against murine
      L929 fibroblasts. TNF alpha has previously been shown to be primarily responsible
      for the lytic activity of such supernatants and this was confirmed. Sulfasalazine
      also inhibited the lytic activity of recombinant TNF alpha. When tested under
      conditions where TNF alpha was allowed to bind to but not lyse the target cells,
      the results suggested that the drug inhibits the action of this cytokine by
      inhibiting its binding to the cell membrane receptor. Additional evidence for an
      inhibitory effect of sulfasalazine on the membrane binding of TNF alpha was
      obtained by demonstrating a dose-dependent displacement of 125I-TNF alpha from
      HL60 cells. Although sulfasalazine is often considered to be a pro-drug for site
      specific delivery of its component fragments 5-ASA and sulfapyridine, the results
      demonstrate an immunopharmacological property of the parent compound that is not
      shared with its component molecules.

PMID- 1981215
TI  - Catecholaminergic, GABAergic, and hippocamposeptal innervation of GABAergic
      "somatospiny" neurons in the rat lateral septal area.
AB  - This study deals with the neurochemical characterization of the rat lateral
      septal area (LSA) somatospiny neurons and their innervation by hippocamposeptal,
      catecholaminergic, and GABAergic fibers. Electron microscopic single and double
      immunostaining methods were used to label catecholaminergic fibers and GABAergic
      cells and boutons. Axon terminals originating in the hippocampus were labeled by
      acute anterograde axon degeneration induced by fimbria-fornix transection 36
      hours before sacrifice. Three types of experiments were performed. The convergent
      catecholaminergic and hippocamposeptal innervation of LSA somatospiny neurons was
      studied by combining immunostaining for tyrosine hydroxylase (TH) with fimbria
      fornix transection. GABAergic neurons and their hippocamposeptal afferents were
      identified and characterized in colchicine pretreated animals immunostained for
      glutamic acid decarboxylase (GAD) combined with fimbria-fornix transection. The
      third experiment aimed at simultaneously visualizing the relationships between
      catecholaminergic boutons, hippocamposeptal excitatory amino acid containing axon
      terminals and GABAergic profiles by double immunostaining for TH (the PAP
      technique) and GAD (the immunogold method) combined with fimbria-fornix
      transection. The results are summarized as follows: 1) The same LSA somatospiny
      neurons receive synaptic inputs from the hippocampus and TH immunoreactive fibers
      which form pericellular baskets around these cells. 2) LSA somatospiny neurons
      are GABAergic and are postsynaptic targets of GABAergic boutons with unknown
      origin and hippocamposeptal axon terminals. 3) The double immunostaining
      experiment, finally, provided direct evidence that the same GABAergic somatospiny
      neurons are postsynaptic targets of both catecholaminergic and hippocamposeptal
      afferents. The synaptic interconnections described in this study provide
      anatomical basis for a better understanding of the action of catecholamines,
      excitatory amino acids, and GABA on the activity of LSA neurons.

PMID- 1981214
TI  - Comparative immunohistochemistry and histochemistry of dipeptidyl peptidase IV in
      rat organs during development.
AB  - The occurrence of dipeptidyl peptidase (DPP) IV during development in Wistar rat
      organs was studied on day 10, 16 and 21 of gestation and on day 1, 4, 8, 13, 21,
      26 and 60 after birth comparing immunohistochemistry and activity histochemistry.
      A polyclonal antibody, as well as monoclonal antibodies recognizing four
      different epitopes (A-D) of the DPP IV molecule, were employed for the
      immunohistochemical studies. In all investigated tissues, immunoreactivity with
      the polyclonal antibody appeared earlier than DPP IV activity and was already
      present on day 10 of gestation in the plasma membranes of embryonic and
      extraembryonic (decidual) cells. At these and other sites, e.g. brain capillary
      endothelium and tracheal or bronchial epithelium, immunoreactivity with the
      polyclonal antibody decreased or disappeared after birth and enzyme activity
      never developed. Immunoreactivity with the monoclonal antibodies appeared later
      than that with the polyclonal antibody, and mostly in those structures where DPP
      IV activity was subsequently found. The monoclonal antibody against epitope D
      showed a high reactivity in the epididymal duct, renal collecting ducts and in
      all domains of the hepatocyte plasma membrane, where neither DPP IV activity nor
      immunoreactivity with the other antibodies were observed. Our results also
      suggest that DPP IV might be present as a molecule before it becomes
      catalytically active and that immunoreactivity occurs at more sites than DPP IV
      activity. However, it cannot be excluded that the polyclonal antibody and the
      monoclonal antibody against the epitope D cross-react with as yet uncharacterized
      proteins, which express common epitopes during embryonic development, but are not
      present in the tissues of adult Wistar rats.

PMID- 1981216
TI  - Tyrosine hydroxylase-like immunoreactivity in the brain of fifth instar Rhodnius
      prolixus Stal (Hemiptera: Reduviidae).
AB  - The distribution of tyrosine hydroxylase-like immunoreactivity was mapped in
      whole-mount preparations of the brain of fifth instar Rhodnius prolixus Stal.
      Immunoreactivity was limited to neuronal cell bodies and processes, which were
      distributed over both ventral and dorsal surfaces of the CNS. The brain,
      excluding the optic lobes, contained about 160 tyrosine hydroxylase-like
      immunoreactive cells. Each optic lobe contained two groups of small round cell
      bodies, which were too numerous to count. The wide distribution of
      immunoreactivity suggests that tyrosine hydroxylase is present in neurons with
      diverse central functions. Tyrosine hydroxylase is the rate-limiting enzyme in
      catecholamine synthesis in vertebrates. A comparison of a map of the distribution
      of catecholamine-induced fluorescence obtained using the glyoxylic-acid technique
      (Flanagan; J. Insect Physiol. 30(9):697-704, 1984) with that generated for
      tyrosine hydroxylase reveals considerable overlap between the two systems,
      suggesting that tyrosine hydroxylase is used in the catecholamine pathway in this
      insect. The mapping of these reactive neurons is an important step for
      identification of unique tyrosine hydroxylase-containing neurons, and is our
      initial step in the analysis of identified catecholamine-containing neurons in R.
      prolixus.

PMID- 1981217
TI  - Peptide-containing nerve fibres in guinea-pig coronary arteries:
      immunohistochemistry, ultrastructure and vasomotility.
AB  - The peptidergic innervation of guinea-pig coronary arteries was investigated by
      means of immunohistochemical, ultrastructural and in vitro pharmacological
      techniques. A network of nerves was demonstrated in all major epicardial arteries
      by means of an antiserum to the neuronal marker protein gene product 9.5. The
      majority of nerve fibres possessed neuropeptide Y (NPY) and tyrosine hydroxylase
      (TH) immunoreactivity, the number and distribution of nerves immunoreactive for
      NPY being similar to that of nerves containing TH immunoreactivity. Numerous
      nerve fibres displaying immunoreactivity for substance P, neuropeptide K and
      calcitonin gene-related peptide (CGRP) were also found. In double-stained
      preparations substance P immunoreactivity was co-localized with CGRP and with
      neuropeptide K immunoreactivities in the same varicose nerve fibres.
      Ultrastructural studies revealed the presence of numerous axon varicosities at
      the adventitial-medial border. NPY immunoreactivity was localized in large
      granular vesicles in nerve varicosities which also contained numerous small
      granular vesicles. Large granular vesicle-containing nerves also displayed
      immunoreactivity for dopamine-beta-hydroxylase. With an in vitro method, the
      vasomotor responses to perivascular peptides were characterized in epicardial and
      intramyocardial arteries. In epicardial arteries neither noradrenaline nor NPY
      elicited a contractile response. Only in some intramyocardial arteries was an NPY
      mediated contraction demonstrated. No potentiating effect of noradrenaline and
      NPY was observed in either epicardial or intramyocardial arterial segments. In
      contrast, CGRP, substance P and vasoactive intestinal peptide (VIP) all produced
      a concentration-dependent relaxation of both epicardial and intramyocardial
      arteries. These results suggest that peptide-containing nerves associated with
      guinea-pig coronary arteries may predominantly be involved in mediating
      vasodilation.

PMID- 1981218
TI  - The Captopril Prevention Project: a prospective intervention trial of angiotensin
      converting enzyme inhibition in the treatment of hypertension. The CAPPP Group.
AB  - The Captopril Prevention Project (CAPPP) is a prospective, randomized, multi
      centre intervention trial designed to investigate whether antihypertensive
      treatment with the angiotensin converting enzyme (ACE) inhibitor captopril may
      reduce cardiovascular mortality and morbidity more than a therapeutic regimen
      which does not include an ACE inhibitor. Secondary objectives are to compare
      total mortality, the development or deterioration of ischaemic heart disease,
      left ventricular failure, atrial fibrillation, diabetes mellitus and possible
      differences in renal function in the two groups. Male and female patients with
      essential hypertension, aged 25-66 years, will be randomly allocated to
      antihypertensive treatment which will comprise either the use of the ACE
      inhibitor captopril or will exclude all types of ACE inhibitors. Some 275
      hypertension centres and health care centres in Sweden and Finland will take part
      in this multi-centre trial. A total of 7000 patients will be recruited and
      studied for an average period of 5 years, the assumption being that a 20%
      difference in cardiovascular mortality between the two groups can be detected
      with a power of 80% at the 5% significance level (two-sided test).

PMID- 1981219
TI  - Characterization of adrenergic receptors of the cat iris and nictitating
      membrane.
AB  - Graded pupillary dilations and nictitating membrane (NM) contractions were
      elicited in anesthetized cats by electrical stimulation of the preganglionic
      sympathetic nerve or by i.a. administration of norepinephrine (NE) or
      phenylephrine into the carotid artery. Pupil and NM responses were measured
      simultaneously from the same side. Alpha-adrenoceptor antagonists were
      administered intravenously. All of the alpha 1-adrenoceptor blockers tested
      produced a dose-related reduction of NM responses to both neural and agonist
      activation; the potency rank order was prazosin greater than WB-4101 greater than
      phentolamine greater than phenoxybenzamine (PBZ). In contrast, responses of the
      iris dilator were antagonized only by WB-4101 and PBZ. The iris was almost
      totally refractory to doses of prazosin and phentolamine that blocked NM
      responses by more than 75% of control. Neither alpha 2- nor beta-adrenoceptor
      antagonism produced significant inhibition of neural or agonist activation of
      either organ (with the exception of high doses of yohimbine on the NM). These
      results suggest that the postjunctional adrenoceptors of the NM are exclusively
      of the alpha 1-adrenoceptor subtype. In contrast, those of the iris dilator
      muscle cannot be easily classified pharmacologically as either alpha 1 or alpha 2
      adrenoceptors.

PMID- 1981220
TI  - Distribution and induction of alkoxyresorufin O-dealkylases and gamma-glutamyl
      transpeptidase in porcine ciliary epithelium.
AB  - Nonpigmented epithelial (NPE) cells and pigmented epithelial (PE) cells were
      separated from porcine ciliary body by a simple surgical procedure. Using primary
      cultures of separated cells, basal and induced activities of 7-ethoxy resorufin
      (ER) O-dealkylase, 7-pentoxy resorufin (PR) O-dealkylase, and gamma-glutamyl
      transpeptidase (GGTP) were determined. These enzymatic activities were primarily
      associated with NPE cells; PE cells showed little or no activity. Treatment of
      NPE cells with phenobarbital for 48 hours resulted in about 5-fold increase in PR
      O-dealkylase activity but not ER-Odealkylase activity. Conversely, 3
      methylcholanthrene treatment increased ER O-dealkylase activity 5-6 times over
      the basal level but had little or nor effect on PR O-dealkylase activity. The
      enhancement of enzymatic activities by inducers was completely inhibited by
      cyclohexamide. NPE cells exhibited higher GGTP activity than PE cells. Both
      phenobarbital and 3-methylcholanthrene augmented the GGTP activity of NPE cells
      but not of PE cells. The physiological significance of the regional differences
      in enzyme distribution was discussed.

PMID- 1981221
TI  - Review: alpha 2 and DA2 agonists as antiglaucoma agents: comparative pharmacology
      and clinical potential.
AB  - Alpha-2 (alpha 2) and DA2 agonists lower intraocular pressure (IOP) in laboratory
      animals and man. Like beta-blockers, alpha 2 and DA2 agonists appear to lower IOP
      by reducing aqueous inflow. These agents share a common mode of action on
      sympathetic nerve terminals, where they modulate the release of
      neurotransmitters. However, one can demonstrate that peripheral prejunctional
      alpha 2 and DA2 receptors on sympathetic neurons are separate entities by
      utilizing selective agonists and antagonists. In addition to their prejunctional
      actions, alpha 2 agonists act postjunctionally in the iris root/ciliary body
      (IRCB). Moreover, utilizing selective postjunctional alpha 2 adrenoceptor
      antagonists, heterogeneity can be demonstrated between ocular pre- and
      postjunctional adrenoceptors. Stimulation of postjunctional alpha 2 adrenoceptors
      in the IRCB can inhibit the cellular responses to endogenous neurotransmitters
      and hormones that are coupled positively to adenylate cyclase. Based upon these
      observations, one can predict that alpha 2 agonists should have a broader
      spectrum of action in the eye than beta-receptor antagonists. Three bioassays
      were used in the activity analysis of alpha 2 and DA2 agonists. Prejunctional
      (neuronal) activity was determined in the cat nictitating membrane preparation in
      which frequency-related (2-8 Hz), neuronally induced contractions were inhibited
      by these compounds. Postjunctional activity was assayed on isolated rabbit IRCB
      tissue where cAMP levels were stimulated by either isoproterenol or VIP in the
      absence and presence of the test agonist (alpha 2 or DA2). In this system, it has
      been demonstrated that alpha 2 agonists have inhibitory properties, but DA2
      agonists are inactive.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1981222
TI  - Plasma carnitine levels in liver cirrhosis: relationship with nutritional status
      and liver damage.
AB  - The plasma level of carnitine, a co-factor involved in many metabolic reactions,
      is high in alcoholic liver cirrhosis, due to an increased amount of esterified
      carnitine. To determine if this alteration is linked to alcoholic liver disease
      or to liver cirrhosis per se. total carnitine, free carnitine, total esterified
      carnitine, short chain acylcarnitine and long chain acylcarnitine were measured
      in 41 patients suffering from liver cirrhosis of different aetiology and
      severity. In 19 of these patients, acetylcarnitine was also measured. Moreover,
      multivariate analysis was performed to assess the association of carnitine plasma
      levels with nutritional and liver disease indices. Of the nutritional indices
      (creatinine/height ratio, mid upper arm muscle circumference and triceps
      skinfold) only triceps skinfold appeared to be weakly correlated with carnitine
      (with long chain acylcarnitine). Significantly high levels of acetylcarnitine,
      short chain acylcarnitine, total esterified carnitine and total carnitine were
      found in cirrhotics independently of the aetiology of cirrhosis, even though a
      trend towards higher levels of acetylcarnitine was evident in heavy drinkers.
      Direct correlations of gamma-glutamyltransferase with acetylcarnitine,
      acetylcarnitine/free carnitine, short chain acylcarnitine/free carnitine and
      total esterified carnitine/free carnitine were found. Carnitine plasma levels did
      not differ in the three Pugh-Child's classes; however, a trend towards higher
      levels of acetylcarnitine was found in Pugh-Child's class C. In conclusion, the
      high levels of acetylcarnitine, short chain acylcarnitine, total esterified
      carnitine and total carnitine found in cirrhosis were linked to liver disease.
      Alcohol abuse seemed only to be an exacerbating factor.

PMID- 1981223
TI  - Secondary prevention of ischemic stroke with low dose acetylsalicylic acid.
AB  - In order to evaluate the efficacy of low dose acetylsalicylic acid (ASA) for the
      secondary prevention of ischemic stroke, this cooperative multicenter clinical
      trial was conducted on a non-blind basis. Patients having a first transient
      ischemic attack (TIA), reversible ischemic neurological deficit (RIND) or
      completed ischemic stroke were eligible for this trial. A total of 590 patients
      including 47 cases of TIA, 23 cases of RIND and 520 cases of completed stroke
      entered this study. These patients were allocated by the time of admission to one
      of the following 5 trial regimens: (1) vasodilators having no known inhibitory
      effect on platelet function (control group), (2) dipyridamole (DP) 50 mg 3 times
      a day (DP group), (3) ASA 300 mg once a day (ASA 300 mg group), (4) ASA 300 mg
      once in combination with DP 50 mg 3 times a day (ASADP group), and (5) ASA 100 mg
      once a day (ASA1 group). No difference in effect between the control and DP
      groups was observed, nor between the ASA 300 mg and ASADP groups. Therefore, we
      combined the control and DP groups to make a non-ASA group, and joined the ASA
      300 mg and ASADP groups to make an ASA3 group. The differences in the cumulative
      event-free rate appeared to be significant between the non-ASA group and the ASA3
      group and also between the non-ASA group and the ASA1 group. But the frequency
      distribution of age, territory of stroke, diabetes mellitus, cardiac disease,
      hematological disease and hyperuricemia were significantly different among these
      3 study groups. We thus included these covariates in the Cox's proportional
      hazard model to control their possible confounding effects.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1981224
TI  - Plasma atrial natriuretic peptide in patients with chronic renal failure.
AB  - Plasma atrial natriuretic peptide (ANP) levels were measured in non-dialyzed and
      dialyzed chronic renal failure (CRF) patients and in normal subjects. Changes in
      plasma ANP in response to hemodialysis (HD) and to isolated ultrafiltration (UF)
      were also investigated in dialyzed CRF patients. Plasma ANP levels were
      significantly higher in 28 non-dialyzed CRF patients than in 27 normal subjects
      (mean +/- SEM, 174.0 +/- 25.9 vs 25.0 +/- 1.9 pg/ml, p less than 0.001). Plasma
      ANP levels did not correlate with blood urea nitrogen or serum creatinine,
      however patients with advanced renal failure (creatinine clearance less than 10
      ml/min) with cardiomegaly (cardiothoracic ratio greater than 50%) or hypertension
      (BP greater than 140/90 mmHg) had significantly higher plasma ANP levels than
      those who were not. A 6-hour HD significantly decreased the plasma ANP level
      (423.4 +/- 71.3 to 220.6 +/- 40.0 pg/ml, p less than 0.001) and body weight in 21
      dialyzed CRF patients, and the decrement in plasma ANP showed a positive
      correlation with the decrement in body weight (r = 0.425, p = 0.056). In 8
      dialyzed CRF patients, we further performed a 1-hour isolated UF for removal of
      isoosmotic intravascular fluid without changes in the solute concentrations,
      followed by a subsequent 5-hour HD. The decrease in plasma ANP during the 1-hour
      UF period was 68% of the total ANP decrement for the whole 6-hour study. The
      average plasma ANP level was decreased with 94.6 +/- 42.5 pg/ml/kg/h in the UF
      period compared to 3.5 +/- 1.4 pg/ml/kg/h in the HD period (p less than
      0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1981225
TI  - Renal excretion of oxalate in patients with chronic renal failure or
      nephrolithiasis.
AB  - This study was carried out in order to investigate renal oxalate excretion in a
      group of normal subjects (n = 40), a group of patients with uremia (n = 52) and a
      group with nephrolithiasis (n = 34). We found that the mean concentrations of
      oxalate in the 24-hour urine specimens of both patient groups were below the
      normal range. Although the renal creatinine clearance (CCR) was significantly
      decreased in some stone patients (n = 14), decreased renal oxalate clearance was
      noted only in those patients with severe renal failure. Thus, plasma oxalate was
      found to be elevated only in patients with chronic renal failure (mean +/- SD,
      49.7 +/- 12.4 mumol/l), while the normal value was 17.0 +/- 6.7 mumol/l. The mean
      tubular excretion fraction of oxalate was also found to increase markedly in
      uremia with a mean of 26.3 +/- 17.3% (in normal subjects, 11.7 +/- 7.5%), but
      their mean daily urinary excretion of oxalate decreased to 63.2 mumol/day (mean
      value of 232.6 mumol/day in normal subjects). A positive correlation was observed
      between oxalate and creatinine, and between oxalate and calcium excretion, which
      was not found in normal subjects or patients with kidney stones. In
      nephrolithiasic patients, the daily excretion of oxalate, calcium and phosphate
      had no discernible increment and the mean excretory ratio of oxalate, calcium or
      phosphate to creatinine was all within normal limits. But when the CCR of stone
      patients was below 80 ml/min, their daily excretion of oxalate and calcium
      decreased significantly (p less than 0.01) and the excretory ratio of phosphate
      to creatinine markedly increased.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1981227
TI  - Antimicrobial activities of six new oral cephem antibiotics.
AB  - Six newly developed oral cephem antibiotics, which included 5 with an
      aminothiazolyl side chain, viz., cefixime, cefotiam hexetil, cefpodoxime
      proxetil, cefteram pivoxil, ceftibuten, and one with a conventional side chain
      design, BMY 28100, were tested for their antimicrobial activities. Three
      traditional oral beta-lactam antibiotics, ampicillin, cephalexin, and cefaclor,
      were used as reference antibiotics. The 5 aminothiazolyl cephems were more active
      than the reference drugs against clinical isolates of Escherichia coli,
      Klebsiella pneumoniae and Haemophilus influenzae. All 6 new drugs showed poor
      activity against clinical isolates of Enterobacter cloacae, Pseudomonas
      aeruginosa, and enterococci. They were better than cephalexin and cefaclor, but
      slightly poorer than or the same as ampicillin in activities against
      Streptococcus pyogenes and Streptococcus pneumoniae. Cefotiam hexetil, BMY 28100,
      and cefpodoxime proxetil were also more active than cephalexin against
      Staphylococcus aureus. Although the 6 tested new oral cephems demonstrated little
      difference in their activities against different bacteria, they all showed
      greater antimicrobial activity than the traditional oral antibiotics now in
      clinical use.

PMID- 1981226
TI  - Assessment of proteinuria by using the protein/creatinine ratio of single-voided
      urine.
AB  - Quantitative 24-hour urine protein excretion is used in the diagnosis, the
      monitoring of therapeutic effects and the prognosis of renal disease. However,
      this method is time-consuming, cumbersome and often inaccurate. Many studies have
      shown that the single voided urine protein/creatinine (Pr/Cr) ratio relates well
      with 24-hour urine protein excretion and can be substituted for evaluating some
      conditions. In our study, 41 patient with renal disease (25 men, 16 women) with a
      mean age of 43 years (range, 20-79 years), not only collected 24-hour urine, but
      also collected single voided urine at four different times. There was an
      excellent correlation between 24-hour urine protein excretion and the single
      voided urine Pr/Cr ratio at various degrees of creatinine clearance and ranges of
      proteinuria. The highest correlation was found in urine specimens collected at
      16:00 hours with a correlation coefficient (r) of 0.91. Other urine specimens
      also showed a good relation with a correlation coefficient of above 0.80. The
      creatinine clearance (Ccr) greater than or equal to 70 ml/min group showed a
      better relationship than the Ccr less than 70 ml/min group. The proteinuria more
      than 1.0 g/day group also showed a better relationship than the group with
      proteinuria of less than 1.0 g/day. However, these differences were not
      statistically significant. No significant differences between the different age
      groups or sexes, using the single voided urine Pr/Cr ratio to estimate the 24
      hour urine protein excretion were found. It is concluded that the single voided
      urine Pr/Cr ratio correlates highly with 24-hour urine protein excretion and
      could be an alternative means for disease monitoring and screening.

PMID- 1981228
TI  - A comparison of diabetic control status between urban and rural diabetic patients
      in Taiwan.
AB  - Between 1985 and 1987, in two urban and five rural areas in Taiwan, a total of
      16,636 subjects aged 40 or over were screened for diabetes mellitus according to
      the WHO criteria. Four hundred and fifty-two previously diagnosed patients and
      274 newly diagnosed patients were found. All were non-insulin-dependent
      diabetics. The blood glucose control status was compared between the urban and
      rural previously diagnosed diabetics. Those living in the rural areas were found
      to have better control with a higher percentage under regular treatment. Stepwise
      multiple regression failed to discover a significant correlation between control
      status and any of the following factors: sex, age, body mass index (BMI),
      diabetic duration, treatment regularity, exercise, occupation, education, family
      income and the presence of hypertension or large vessel diseases. About 30% of
      the patients in rural areas and 40% in urban areas were poorly controlled. This
      indicates that our diabetic control program should be strengthened.

PMID- 1981229
TI  - Effect of dietary therapy on pancreatic beta cell function in noninsulin
      dependent diabetes mellitus.
AB  - Twenty-four noninsulin-dependent diabetics, who were newly diagnosed or had
      discontinued therapy for at least 10 months, were studied for the effect of
      dietary therapy on pancreatic beta cell function. The mean fasting plasma glucose
      (176 +/- 14 vs 212 +/- 16 mg/dl, p less than 0.01) and glycosylated hemoglobin
      (HbA1c, 8.6 +/- 0.5 vs 9.4 +/- 0.6%, p less than 0.001) decreased significantly
      after 1 month of dietary control, although there was no significant change in
      mean body weight (57.4 +/- 2.0 vs 57.7 +/- 2.0 kg, p greater than 0.5). The mean
      incremental serum C-peptide (delta CP) response to oral glucose stimulation
      (OGTT) increased (4.6 +/- 0.6 vs 3.5 +/- 0.7 ng/ml, p less than 0.01), but that
      to intravenous glucagon (GT) did not (2.5 +/- 0.2 vs 2.7 +/- 0.2 ng/ml, p greater
      than 0.1). In 12 patients whose glycemic control improved after dietary
      treatment, there was a good correlation between the decrement in fasting plasma
      glucose and the increment in delta CP response to OGTT (r = 0.66, p less than
      0.05). IN CONCLUSION: after 1 month of dietary therapy in noninsulin-dependent
      diabetics, (1) the serum C-peptide response to OGTT, but not to GT, improved; (2)
      the beta cell secretion increased only in those patients with improved glycemic
      control; (3) there was a good correlation between glycemic control and beta cell
      function.

PMID- 1981230
TI  - Serum copper and zinc levels in patients with cervical cancer.
AB  - The serum copper (SCL) and zinc (SZL) levels were measured in 99 patients with
      cervical cancer and 50 patients with uterine myoma as controls. The mean SCL in
      the control group was 109.4 +/- 17.4 micrograms/ml as compared to 117.1 +/- 14.6
      micrograms/dl and was not significant (NS) in 17 carcinoma in situ (CIS)
      patients, 142.3 +/- 14.2 micrograms/dl in 30 stage I patients (p less than
      0.001), 159.0 +/- 16.6 micrograms/dl in 22 stage II patients (p less than 0.001),
      171.6 +/- 25.7 micrograms/dl in 10 stage III or IV patients (p less than 0.001),
      and 166.2 +/- 32.2 micrograms/dl in 20 recurrent patients (p less than 0.001).
      The SCL returned to control level 2 weeks after surgical treatment for the stage
      I and II patients (mean 110.6 +/- 19.6 and 108.7 +/- 20.4 micrograms/dl,
      respectively, p less than 0.001). The SZL was 97.2 +/- 15.8 micrograms/dl in
      control patients and only showed a significant decrease in stage III or IV and
      recurrent patients (67.2 +/- 16.6 and 70.4 +/- 17.2 micrograms/dl, respectively).
      Concerning the copper/zinc ratio, the control group was 1.13 +/- 0.07 as compared
      to 1.17 +/- 0.07 in CIS (p = 0.06), 1.51 +/- 0.24 in stage I (p less than 0.001),
      1.85 +/- 0.37 in stage II (p less than 0.001), 2.66 +/- 0.61 in stage III or IV
      (p less than 0.001), and 2.50 +/- 0.75 in recurrent patients (p less than 0.001).
      Taking mean +/- 2.5 SD of the control values as cut off points, the percentages
      of the recurrent patients with abnormal SCL, SZL, and a Cu/Zn ratio were 65, 30
      and 90%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1981231
TI  - Evaluation of urease test, gram stain, culture, and histology in the detection of
      Campylobacter pylori.
AB  - To evaluate the commonly available tests for detection of Campylobacter pylori
      infection in the human stomach, we prospectively performed endoscopy and biopsy
      from the antrum of the stomach in 121 consecutive patients. Four tests, including
      the urease test, Gram stain, culture, and the hematoxylin and eosin (H & E) stain
      were used to detect the presence of C. pylori. A C. pylori positive was defined
      by a positive culture or positive results in two of the other three tests. The
      sensitivity of the urease test, Gram stain, culture, and H & E stain was 95%,
      95%, 71%, and 97%, respectively, and the specificity of those tests was 96%,
      100%, 100%, and 73%, respectively. For diagnosis, theoretically, all four tests
      should be performed from the biopsy specimens. In our experience, the culture was
      less sensitive, and the H & E stain was less specific, while the urease test and
      Gram stain were more rapid and had high sensitivity and specificity in the
      detection of C. pylori infection.

PMID- 1981232
TI  - Surgical treatment of tibial shaft fracture: experience of 207 cases.
AB  - From January 1984 to March 1988, 210 tibial shaft fractures in 207 patients
      treated by intramedullary nails, and by plate and screws and extraskeletal
      fixation were studied. There were 166 men and 41 women. Of the fractures, 95
      (42.2%) of the 210 tibial shaft fractures were closed fractures and 115 (54.8%)
      were open fractures [Grade I: 44 (21.0%), Grade II: 39 (18.6%), and Grade III: 32
      (15.2%)]. The incidence of associated injury was 44.3% and it was highest in the
      group with extraskeletal fixation (64.7%). Intramedullary nailing was performed
      in the majority of these fractures (127 out of 210) and yielded the best results
      in this series. Kuntscher's nailing resulted in nonunion in 3 cases (2.8%),
      superficial infections in 3 cases (2.8%) and deep infections in 4 cases (3.8%).
      Interlocking nailing resulted in nonunion in 1 case (4.8%), superficial infection
      in 1 case (4.8%) and deep infections in 3 cases (14.3%). Plate and screws
      fixation was performed primarily for metaphyseal fractures (71.4%) and resulted
      in nonunion in 4 cases (8.1%), superficial infection in 1 case (2.0%) and deep
      infection in 5 (10.2%). In the group treated with extraskeletal fixation,
      inasmuch as there were more cases of compromised soft tissue (open fracture,
      97.1%), a higher incidence of associated major injuries (64.7%) and more cases of
      comminution of the bone (67.6%), the final results were less satisfactory.
      Nonunion was noted in 26.5% of the cases, superficial infection in 2.9% of the
      cases, and deep infection in 32.4% of the cases. From our study, we conclude that
      in appropriately selected patients, surgical fixation of tibial shaft fractures
      can produce a good functional recovery with an acceptable low rate of
      complications.

PMID- 1981234
TI  - Retroperitoneal neurilemoma: clinical features in 10 cases.
AB  - Neurilemoma is a rare tumor in the retroperitoneal cavity. Up to 1984, less than
      50 cases had been reported in the English literature. We observed 10 cases of
      retroperitoneal neurilemoma with histologic proof at our hospital. The major
      symptoms were abdominal pain (80%) and body weight loss (40%). Physically
      palpable abdominal masses were found in 90% of the cases. The laboratory data
      were all within normal limits, except for a mild elevation of the eosinophil
      count in 4 cases. Radiologic examination demonstrated the tumor in most cases.
      Abdominal ultrasonography was very effective in the detection of these tumors.
      Surgical resection was the treatment of choice. Some patients suffered from leg
      numbness after the operation. Recurrent rate was high, up to 20% therefore, long
      term follow-up is mandatory.

PMID- 1981233
TI  - Carpal bone dislocations: review of 20 cases.
AB  - Twenty cases of carpal bone dislocation were encountered during a 7-year period,
      with an average of 27 months of follow-up. There were 10 types of dislocation in
      this series, the most common type was transscaphoid perilunate dislocation seen
      in 9 cases. In addition, there were 2 scaphoid subluxations, 1 volar lunate
      dislocation, 1 dorsal perilunate dislocation, 1 scaphoid perilunate dislocation,
      1 hamate and pisiform dislocation, 1 transhamate pisiform dislocation, 1
      trapezoid and 2-5 carpometacarpal joint dislocation, 1 trapezium, trapezoid and 2
      4 carpometacarpal joint dislocation, and 2 trapezium periscapholunate
      dislocations. Methods of treatment included open reduction, closed reduction,
      proximal row carpectomy, total wrist arthrodesis, and excision of the lunate. In
      this series, the patterns of dislocation were different for crushing injuries and
      dorsiflexion injuries. The clinical results associated with the soft tissue
      injuries of the ipsilateral hand were mostly caused by crushing forces. Although
      carpal instabilities were noted, there was no significant correlation between the
      clinical and radiographic results in some of our cases. Best results invariably
      relied on a stable anatomic reduction and an adequate period of immobilization.
      Poor results were demonstrated in those cases with incomplete initial reduction,
      secondary degenerative arthrosis, or nonunion.

PMID- 1981235
TI  - Pregnancy induces the presence of a thyroid-stimulating antibody in a thyrotropin
      binding inhibitory immunoglobulin positive, hypothyroid woman with transient
      thyrotoxicosis in offspring.
AB  - A 27-year-old woman had a goiter and transient hyperthyroidism when she was 18
      years old. Symptoms subsided after treatment with medication (without use of
      radioactive iodine) for one month. She delivered a child without complications at
      23 years of age. Hypothyroidism developed when she was 25 years old. Under the
      impression of autoimmune thyroiditis with hypothyroidism, she was treated with
      levothyroxine 150 micrograms/day. She became pregnant again one year later. Her
      thyrotropin-binding inhibitory immunoglobulin (TBII) was very high before and
      during pregnancy, and after delivery. Thyroid-stimulating antibody (TSAb) was not
      detectable during the 2nd trimester, but elevated in association with a decrease
      in dosage of levothyroxine during the 3rd trimester. She delivered a male baby at
      full-term. The newborn's TBII was high at 4 days old and it gradually developed
      into hyperthyroidism with symptoms of irritability, poor weight gain, tachycardia
      and jaundice. Hyperthyroidism subsided after temporary treatment with methimazole
      and propranolol. The medication was discontinued at the age of 82 days. Follow-up
      thyroid function was normal at the age of three and a half months. In the mother,
      TSAb gradually decreased, although TBII was still very high. The dosage of
      levothyroxine was again increased. This study demonstrates that pregnancy may
      alter the ratio of TBII and TSAb, and modify the functional state of the thyroid
      of the mother. Therefore, in patients with autoimmune thyroiditis during
      pregnancy, serial follow-up of thyroid function and TBII (and TSAb, if possible)
      may help the doctor to properly adjust the treatment.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1981236
TI  - Albright's syndrome with acromegaly and Hashimoto's thyroiditis: report of a
      case.
AB  - The case of a 35-year-old woman with Albright's syndrome, acromegaly and
      Hashimoto's thyroiditis is presented. She had noted deformity of the left
      mandible and chest from childhood. She developed persistent galactorrhea and
      amenorrhea after the delivery of her second child. X ray of the skull, and a head
      CT, revealed a pituitary tumor and fibrous dysplasia of the left mandible,
      sphenoid, zygomatic bone and pteryoid plate. Serum GH and PRL levels were
      markedly elevated. She received recontouring surgery of the left mandible, and a
      pathological examination confirmed the diagnosis of fibrous dysplasia. Chest X
      ray also showed fibrous dysplastic change of the left 4th, 5th, 6th and 7th ribs
      and left clavicle. Because of poor response to bromocriptine, she received a
      craniotomy to remove the pituitary macroadenoma. Pathological examination of the
      tumor revealed an acidophilic tumor. Postoperative radiotherapy was given for
      residual active tumor. She developed adrenal crisis two months after radiotherapy
      when she discontinued replacement therapy. The diagnosis of Hashimoto's
      thyroiditis was arrived at by palpation of the goiter, elevated thyroid
      antibodies, ultrasound pictures of the thyroid, fine needle aspiration cytology
      and hypothyroidism. To our knowledge, this is the first report of Albright's
      syndrome with Hashimoto's thyroiditis. The hypothesis of autoimmune disease is
      proposed to explain the hypofunction of the endocrine glands associated with
      Albright's syndrome.

PMID- 1981237
TI  - Primary myelofibrosis in children: report of 4 cases.
AB  - From 1982 to 1985, four cases of primary myelofibrosis were diagnosed in our
      department. Three were boys and one was a girl. Their ages ranged from 7 months
      to 15 years. The diagnosis was made based on anemia, leukoerythroblastic change
      and presence of giant platelets in the peripheral blood, and a bone marrow biopsy
      showing myelofibrosis. Most of them had anemia, fever, and hepatosplenomegaly on
      admission. The anemia was severe and refractory to repeated transfusions and
      steroid therapy in 3 out of the 4 cases. Splenectomy was performed in 1 case, but
      without satisfactory results. The clinical course and blood pictures in one case
      resembled leukemia of megakaryocyte lineage (M7), but results of marker studies
      of the blast cells ruled out the possibility of M7. Three of them underwent
      leukemic transformation within 2 years and died soon after. The other one died of
      sepsis 2 weeks after diagnosis. Myelofibrosis in childhood occurs rarely,
      however, when it does, it always runs a rapid and fatal course.

PMID- 1981238
TI  - Sleeve resection of congenital tracheal stenosis associated with pulmonary artery
      sling: report of a case.
AB  - A 20-month-old boy was diagnosed as having congenital tracheal stenosis
      associated with left pulmonary artery sling. A tracheal segmental resection with
      transposition of the left pulmonary artery out of the vascular sling via right
      thoracotomy was performed using high frequency jet ventilation. The above
      procedure was used instead of traditional vascular transposition through a left
      thoracotomy. Postoperatively, the bronchoscopic view of the trachea was patent.

PMID- 1981239
TI  - Proliferating cell nuclear antigen (PCNA) immunolocalization in paraffin
      sections: an index of cell proliferation with evidence of deregulated expression
      in some neoplasms.
AB  - Proliferating cell nuclear antigen (PCNA) is a 36 kD nuclear protein associated
      with the cell cycle. A monoclonal antibody, PC10, that recognizes a fixation and
      processing resistant epitope has been used to investigate its tissue
      distribution. Nuclear PCNA immunoreactivity is found in the proliferative
      compartment of normal tissues. PCNA immunoreactivity is induced in lectin
      stimulated peripheral blood mononuclear cells in parallel with bromodeoxyuridine
      incorporation and the number of cells with PCNA immunoreactivity is reduced by
      induction of differentiation in HL60 cells. In non-Hodgkin's lymphomas a linear
      relation between Ki67 and PCNA staining was demonstrated. These data suggest that
      in normal tissues and lymphoid neoplasms, PCNA immunolocalization can be used as
      an index of cell proliferation. However, in some forms of neoplasia, including
      breast and gastric cancer and in vitro cell lines, the simple relation between
      PCNA expression and cell proliferation is lost. In some breast and pancreatic
      tumours there is apparent deregulation of PCNA with increased expression in
      tissues adjacent to the tumours. The over-expression in some tumours and in
      adjacent morphologically normal tissue may represent autocrine or paracrine
      growth factor influence on PCNA gene expression.

PMID- 1981240
TI  - Phenotypic markers of lymphocyte and mononuclear phagocyte activation within
      rheumatoid nodules.
AB  - We investigated rheumatoid subcutaneous nodules using monoclonal antibodies
      recognizing functional determinants on mononuclear phagocytes (Mph) and
      lymphocytes. Mph at the center of rheumatoid nodules showed strong expression of
      the leukocyte intergrins CR3 and p150,95 which would be consistent with the
      presence of a central chemotactic stimulus. Mph expression of FcR1, a gamma
      interferon regulated molecule, was decreased in 5/13 cases despite strong
      expression of MHC class II. There was a variable unstructured infiltrate of T
      lymphocytes, a majority of which were CD8 positive. Lymphocytes showed increased
      MHC class II expression but interleukin 2 receptor expression was low. We
      discerned no relationship between the number, distribution or phenotype of the T
      cell infiltrate and the phenotype of the predominant Mph population.

PMID- 1981241
TI  - Responses of the colonic epithelium to auranofin: evidence for involvement of
      enteric nerves.
AB  - Auranofin, the orally effective gold compound, stimulated the canine colonic
      epithelium in vitro. It increased short circuit currents across both the
      innervated mucosal and functionally "nerve-free" epithelial preparation, when
      added to either the luminal or serosal solutions. Serosal responses were
      inhibited by tetrodotoxin (TTX). A hydrophilic gold compound, sodium
      aurothiosulphate produced similar effects but only on serosal addition. Gold
      compounds can thus alter colonic transport activating enteric nerves and
      releasing a neurotransmitter. Thus gold induced diarrhea could have a significant
      neural component.

PMID- 1981243
TI  - Aortitis syndrome (Takayasu's arteritis) associated with SLE.

PMID- 1981242
TI  - The effect of antirheumatic drugs on interleukin 1 (IL-1) activity and IL-1 and
      IL-1 inhibitor production by human monocytes.
AB  - Interleukin 1 (IL-1) is an important mediator of immune regulation, inflammation
      and joint destruction in arthritis. The objective of our study was to investigate
      the effect of a number of representative antirheumatic agents on the activity of
      IL-1 and the production of both IL-1 and IL-1 inhibitor by human monocytes. IL-1
      activity and production were measured by its effect on the proliferation of
      murine thymocytes; IL-1 inhibitor production was assayed by inhibition of IL-1
      mediated thymocyte proliferation. Dexamethasone (10-100 nM) inhibited IL-1
      production and IL-1 mediated thymocyte proliferation. High concentrations of
      indomethacin, aspirin, and 12 other nonsteroidal antiinflammatory drugs (NSAID)
      inhibited IL-1 activity, or production or both. Methotrexate inhibited IL-1
      activity without affecting IL-1 production. D-penicillamine inhibited IL-1
      activity and tended to inhibit IL-1 production. Gold compounds inhibited IL-1
      activity, but only auranofin inhibited IL-1 production. Acetaminophen in high
      concentrations (1 mg/ml) inhibited IL-1 activity and production. Colchicine
      inhibited IL-1 activity but not IL-1 production. No drug tested induced, by
      itself, the production of IL-1 inhibitor or enhanced the production of IL-1
      inhibitor.

PMID- 1981244
TI  - Chronic pain and substance abuse: a pilot study of opioid maintenance.
AB  - Recent reports suggest that opioid maintenance may be appropriate for treatment
      resistant patients with chronic nonmalignant pain syndromes. However, a history
      of substance abuse is thought to be a contraindication for such treatment. We
      present a pilot study of a methadone maintenance-type treatment for patients with
      both chronic pain and substance abuse, evaluating the ability to attract and hold
      patients, the methodology for assessing change, and the potential problems and
      pitfalls. Weekly random urinalysis, weekly psychotherapy, and quarterly self
      report tests of pain, mood, and function were used to evaluate change. Three out
      of 4 patients remained in treatment for 19-21 months, stopped needle use, and/or
      markedly decreased substance abuse, and appear to have improved functionally.
      Surprisingly, all 3 patients had significant psychopathology requiring treatment
      with psychotropic medication. This treatment may warrant further research.

PMID- 1981246
TI  - [Diagnosis of hemorrhagic fever with renal syndrome].
AB  - The authors observed 22 patients with hemorrhagic fever with the renal syndrome
      (HFRS). The diagnosis turned out to be difficult in outpatient clinics as all the
      patients were referred to hospital with erroneous diagnoses. Epidemiological
      causes of infection of HFRS were indicated. The authors singled out 3 periods in
      a course of this disease with characteristic symptoms. The diagnosis was
      confirmed serologically in the reaction of indirect immunofluorescence, a 4-fold
      increase and over in antibody titer was observed. A case history was presented.

PMID- 1981245
TI  - Heterosexual transmission of HIV in hemophiliacs.
AB  - Of 686 hemophiliacs who are being treated at our institution, 402 (59%) are HIV
      sero-positive. One hundred seventy-eight heterosexual partners of HIV-infected
      hemophiliacs have been serologically examined; 19 (11%) are HIV-positive. So far
      none of the seropositive partners suffers from ARC or AIDS. The rate of
      heterosexual transmission of HIV is statistically significantly correlated with
      the CD4+ count of the HIV-infected index patient. No such correlation was found
      with the index patient's clinical stage or the isolation of HIV from the index
      patient's blood. Of 39 seronegative female partners who were investigated
      clinically and immunologically, 17 showed pathologically increased numbers of
      CD8+ counts. In one case, HIV was transmitted from a female patient with von
      Willebrand's disease to her husband. As compared to other groups at risk for
      AIDS, the rate of heterosexual HIV transmission is comparatively low in
      hemophiliacs. The exact reason for this difference is not yet known. The
      relevance of the immunopathological findings in seronegative sexual partners of
      hemophiliacs also remains to be determined.

PMID- 1981247
TI  - [2 cases of fibrosing alveolitis in patients with rheumatoid arthritis treated
      with chrysanol].

PMID- 1981248
TI  - [Activation of transcription of the tyrosine aminotransferase gene in the rat McA
      RN 7777 hepatoma cell line by cycloheximide].
AB  - The expression of the tyrosine aminotransferase (TAT) mRNA after cycloheximide
      treatment was analysed by Northern blotting method in Morris rat hepatoma cell
      lines. The level of TAT mRNA increased after 6-8 h of cycloheximide treatment
      only in the McA-RH 7777 cell line. McA-RH 7777 nuclear run-off assay showed that
      TAT transcription was induced by cycloheximide treatment. Both glucocorticoid and
      cycloheximide modulated TAT gene transcription in a synergistic way. There was no
      induction of TAT expression following cycloheximide or cycloheximide
      glucocorticoid simultaneous treatment in another cell line (McA-RH 8994), while c
      myc and c-fos expression was superinduced by cycloheximide treatment. The
      possible mechanism of transcription regulation and its damage in hepatoma cells
      is discussed.

PMID- 1981249
TI  - Molecular analysis of selection for benzimidazole resistance in the sheep
      parasite Haemonchus contortus.
AB  - The molecular basis for the resistance of the sheep parasitic nematode Haemonchus
      contortus to the benzimidazole (BZ) group of anthelmintics was investigated.
      Three BZ-susceptible and three resistant populations from different geographical
      locations were characterized with respect to the egg-hatch assay with
      thiabendazole (TBZ), mebendazole (MBZ) binding tests and restriction fragment
      length polymorphism (RFLP) after Southern blotting. Cloned H. contortus alpha-
      and beta-tubulin genes were used as probes to analyze the RFLPs of genomic DNA
      prepared from mixtures of infectious larvae (L3) or adults. The susceptible
      populations showed, with both alpha- and beta-tubulin probes, 2 to 6 different
      fragments, depending on the restriction enzyme used. The three resistant
      populations showed as many fragments with the alpha-tubulin probe as the
      susceptible populations, but when probed with beta-tubulin only 1 or 2 fragments
      were visible, but always less than in the susceptible populations. An in vitro
      selection experiment was carried out using a susceptible population that was
      isolated in the laboratory before BZ came on the market. The results showed that
      after two selections with increasing amounts of TBZ, the population had become
      resistant, according to the egg-hatch assay values and MBZ binding assay. Using
      RFPL, the number of beta-tubulin probe reactive DNA fragments was reduced from 5
      to 1. Analysis of the DNA of individual male adults of susceptible populations
      indicated a heterogeneity among the individual worms regarding the number of beta
      tubulin probe reactive fragments (1 to 4) and frequency of the specific
      fragments. Usually, only one specific fragment (9 kb) was found in the resistant
      individuals. This 9-kb fragment was already present in some individuals in the
      susceptible population although it was in combination with other fragments. This
      would imply that genes conferring BZ resistance were present in H. contortus
      populations before BZ came on the market, and could explain the fast selection
      for BZ resistance in the field.

PMID- 1981250
TI  - [Neuroleptic-induced palilalia. A currently undescribed side effect].

PMID- 1981251
TI  - Workshop on neurologic complications of pertussis and pertussis vaccination.
AB  - A multidisciplinary workshop held from September 29 to October 1, 1989, at Airlie
      House, Warrenton, Virginia, considered the neurologic complications of whooping
      cough and pertussis vaccine. Pertussis mortality in the U.S. in 2-3/1000 cases.
      Seizures occur in 1.9% of cases, and encephalopathy in 0.3%. Reviewing all data,
      it appears likely that a combination of one or more bacterial toxins, asphyxia,
      CO2 retention and loss of cerebral vascular autoregulation is responsible for
      neurologic symptoms. The timing of the encephalopathy suggests that it results
      from increased lysis of bacteria, and release of endotoxin. The encephalopathy is
      not confined to the paroxysmal phase. In evaluating side-reactions to the
      vaccine, the following must be kept in mind: 1. Vaccines are not standardized
      between manufacturers. 2. For a given manufacturer, vaccines are not standard
      from one batch to the next. 3. Unless the vaccine is properly prepared and
      refrigerated, its potency and reactivity varies with shelf life. In fact, the
      whole question of vaccine detoxification has never been systematically
      investigated. Listed in order of increasing severity, observed adverse reactions
      include irritability, persistent, unusually high pitched crying, somnolence,
      seizures, a shock-like "hypotensive, hyporesponsive" state, and an
      encephalopathy. Since the neurologic picture is not specific for pertussis
      vaccination, its temporal relationship to the vaccination is the critical
      variable for determining causation. Although the majority of seizures following
      pertussis vaccination are associated with fever, it was the consensus of the
      neurologists attending the workshop, that these do not represent febrile
      convulsions, but are non-benign convulsions. The incidence of post-vaccine
      encephalopathy is difficult to ascertain.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1981252
TI  - The non-competitive NMDA-receptor antagonist MK-801 prevents the massive release
      of glutamate and aspartate from rat striatum induced by 1-methyl-4
      phenylpyridinium (MPP+).
AB  - The concentrations of dopamine (DA) and of the excitatory amino acids (EAAs)
      glutamate (Glu) and aspartate (Asp) were measured in dialysates from the striatum
      of awake rats in order to study the link between the release of DA and of EAAs
      induced by the infusion of 1-methyl-4-phenylpyridinium ion (MPP+). DA and EAAs
      were detected simultaneously by HPLC-EC. The infusion of MPP+ at the
      concentration of 1 mM elevated DA levels in the perfusates, but did not affect
      EAA release. However, MPP+ at 10 mM maximally stimulated Glu and Asp release to
      230- and 68-fold of baseline, respectively. In this condition, pretreatment with
      the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 (5 mg/kg, i.p.)
      prevented the MPP(+)-induced EAA release. In contrast, MK-801 had no effect on DA
      release induced either by 1 or 10 mM MPP+. These results suggest that MPP(+)
      induced DA and EAA release are independently regulated processes. In addition,
      the finding that MK-801 inhibits MPP(+)-induced EAA release suggests that EAAs
      may act on NMDA receptors to stimulate their own release through a positive
      feedback mechanism.

PMID- 1981253
TI  - GABA receptor modulation of tyrosine hydroxylase gene expression in the rat
      adrenal gland.
AB  - Chromaffin cell gamma-aminobutyric acid (GABA) receptors play a role in
      modulating catecholamine secretion. The present experiments examined the role of
      GABA receptors in modulation of tyrosine hydroxylase (TH) induction in rat
      adrenal gland. Administration of bicuculline, a GABA antagonist, had no effect on
      TH activity or TH mRNA. However, bicuculline potentiated reserpine's effect on TH
      activity and TH mRNA induction. These data suggest that GABA receptors modulate
      induction of TH and TH mRNA in the adrenal gland.

PMID- 1981254
TI  - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced damage of striatal
      dopaminergic fibers attenuates subsequent astrocyte response to MPTP.
AB  - Acute administration of the dopaminergic neurotoxicant 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP) to the C57BL/6 mouse caused a rapid decrease in the
      amount of striatal tyrosine hydroxylase (TH), a marker of the nigrostriatal
      dopaminergic pathway, followed by a large increase in the astrocyte protein,
      glial fibrillary acidic protein (GFAP). The astrocyte (GFAP) response declined to
      baseline three weeks after administration of MPTP. Administration of a second
      dosage of MPTP at this time evoked a second GFAP response. The magnitude of the
      second response, however, was decreased in comparison to the response seen after
      only a single exposure to MPTP. Increasing the initial dosage of MPTP resulted in
      greater reductions of the second GFAP response. These data indicate that MPTP
      induced damage or loss of striatal dopaminergic neurons reduces the signal
      available for initiating astrogliosis and thereby reduces the astrocyte response
      to a second exposure to MPTP.

PMID- 1981255
TI  - Glycine facilitates induction of long-term potentiation of evoked potential in
      rat hippocampus.
AB  - Effects of glycine were investigated in Schaffer/commissural-CA1 pyramidal cell
      synapses of the rat hippocampal slices. Perfusion of glycine (0.05 mM) did not
      change baseline population spikes evoked by test stimulation but significantly
      enhanced short-term potentiation induced by a single shorter tetanus (100 Hz, 11
      impulses); the effects resulted in production of long-term potentiation (LTP).
      LTP produced by a longer tetanus (100 Hz, 100 impulses, 2 trains) was not
      significantly influenced. Higher concentration (0.5 mM) of glycine increased the
      baseline spike amplitude. All these effects of glycine were not observed in the
      presence of 10(-5) M 2-amino-5-phosphonovalerate, an N-methyl-D-aspartate (NMDA)
      antagonist. These results demonstrate that glycine can facilitate induction of
      LTP probably by activating NMDA receptor.

PMID- 1981256
TI  - Antianxiety agents: a historical perspective.

PMID- 1981257
TI  - Novel anxiolytic agents: actions on specific subtypes of central 5-HT receptors.

PMID- 1981258
TI  - Serenics, serotonin and aggression.

PMID- 1981259
TI  - Mechanism based approaches to anticonvulsant therapies: modulation of inhibitory
      and excitatory transmission.

PMID- 1981260
TI  - CGP 37849 and CGP 39551: novel competitive N-methyl-D-aspartate receptor
      antagonists with potent oral anticonvulsant activity.

PMID- 1981261
TI  - Gepirone hydrochloride: preclinical pharmacology and recent clinical findings.

PMID- 1981262
TI  - Mechanism-based approaches to anticonvulsant therapy.

PMID- 1981263
TI  - Pharmacology of the serotonergic anxiolytic tandospirone (SM-3997).

PMID- 1981264
TI  - Ipsapirone: a novel anxiolytic and selective 5-HT1A receptor ligand.

PMID- 1981265
TI  - CGS 18102A, a benzopyranopyridine anxiolytic with 5-HT1 agonist and 5-HT2
      antagonist properties.

PMID- 1981266
TI  - CGS 20625, a novel pyrazolopyridine with selective anxiolytic activity.

PMID- 1981267
TI  - A novel potent non-benzodiazepine anxioselective agent with reduced dependence
      liability: ICI 198, 256.
AB  - ICI 198,256, a member of the cinnoline series, was shown to be a potent
      anxiolytic agent in several species of animals. In addition, ICI 198,256
      exhibited potent activity as an antagonist of both metrazole and bicuculline
      induced convulsions. The salient features of ICI 198,256 are that it possesses
      minimal sedative liability, lower ethanol interaction and possibly lower
      dependence liability than benzodiazepines (e.g., diazepam). Neurochemically, this
      structurally novel anxiolytic compound is potent and selective for the Type 1
      (cerebellar) BZ receptors in vivo as well as ex vivo, and in addition shows an
      agonist BZ-like profile in a variety of systems. Thus, ICI 198,256 may offer
      several significant advantages in the treatment of anxiety in humans than
      existing benzodiazepines.

PMID- 1981268
TI  - Preclinical anxiolytic profiles of 7189 and 8319, novel non-competitive NMDA
      antagonists.
AB  - Antagonists at excitatory amino acid receptors, especially the N-methyl-d
      aspartate (NMDA) subtype, have been shown to possess anticonvulsant and
      anxiolytic properties (Clineschmidt et al., 1982; Croucher et al., 1982; Bennett
      and Amrick, 1986). 7189 and 8319, two closely related benzeneethanamines, are
      potential novel anxiolytic agents which bind with high affinity to the NMDA
      receptor at the non-competitive site and are relatively non-toxic (LD50's-160
      mg/kg, ip). 7189 and 8319 showed anxiolytic effects in schedule controlled
      conflict assays as well as in the social interaction (SI) and elevated plus maze
      (EPM) procedures in rats. Following intraperitoneal administration of 7189 at 20
      to 60 mg/kg, conflict responding was increased from 2- to 7-fold in the modified
      Cook and Davidson and Geller conflict paradigms. 8319, at 2.5 to 5 mg/kg,
      produced a two fold increase in conflict responding. In the non-schedule
      controlled procedures, 7189 at 20 mg/kg increased SI time by 23% while in the EPM
      at 10 to 20 mg/kg, open arm exploration time increased by 41 to 77%. Likewise,
      8319 at 2.5 and 5 mg/kg increased open arm exploration and SI time by 50 and 37%,
      respectively. In summary, 7189 and 8319 were efficacious in four behavioral
      procedures predictive of potential anxiolytic agents. Although these compounds
      have not been submitted for clinical evaluation, they may represent a new class
      of beneficial compounds for the treatment of anxiety.

PMID- 1981270
TI  - Training in medical psychotherapy: cross-cultural diversity. Selected papers of
      the 14th International Congress of Medical Psychotherapy. Lausanne, October 9-15,
      1988.

PMID- 1981269
TI  - CGS 19755: a novel competitive N-methyl-D-aspartate (NMDA) receptor antagonist
      with anticonvulsant, anxiolytic and anti-ischemic properties.
AB  - CGS 19755 is a potent and selective competitive antagonist at NMDA receptors in
      the brain. In preclinical animal tests, the compound produces anticonvulsant,
      anxiolytic and anti-ischemic effects. CGS 19755 is not very active when
      administered orally, and intravenous administration is the most practical for
      clinical application. The anti-ischemic potential of CGS 19755 provides the most
      attractive application for clinical investigation.

PMID- 1981271
TI  - Grafting genetically modified cells to the brain: conceptual and technical
      issues.

PMID- 1981272
TI  - IIIrd International Symposium on Neural Transplantation. Cambridge, 6-11 August,
      1989. Proceedings.

PMID- 1981273
TI  - Genetically altered and defined cell lines for transplantation in animal models
      of Parkinson's disease.

PMID- 1981274
TI  - The effect of site of transplantation and histocompatibility differences on the
      survival of neural tissue transplanted to the CNS of defined inbred rat strains.

PMID- 1981275
TI  - Allograft rejection overcome by immunoselection of neuronal precursor cells.

PMID- 1981277
TI  - Response characteristics of neocortical graft neurons to host somatosensory
      input.

PMID- 1981276
TI  - Exogeneous expression of L-dopa and dopamine in various cell lines following
      transfer of rat and human tyrosine hydroxylase cDNA: grafting in an animal model
      of Parkinson's disease.

PMID- 1981278
TI  - Cellular reaggregation in vivo: modular patterns in intrastriatal grafts derived
      from fetal striatal primordia.

PMID- 1981279
TI  - Cellular localisation of neurotransmitter mRNAs in striatal grafts.

PMID- 1981280
TI  - Connectivities of the striatal grafts and laminin guiding.

PMID- 1981281
TI  - Neural transplantation (auto-adrenal, fetal nigral and fetal adrenal) in
      Parkinson's disease: the Mexican experience.

PMID- 1981282
TI  - Benzodiazepine augmentation of the treatment of disruptive psychotic behavior.

PMID- 1981284
TI  - [XIIIth annual meeting of the French Society of Rhumatologie and the Third French
      Congress of Rhumatologie. Paris, 22-24 November 1990. Abstracts].

PMID- 1981285
TI  - The Second European Symposium on Stone Disease, Basle, 22-24 March 1990.

PMID- 1981283
TI  - Role of neurotransmitters in the central regulation of the cardiovascular system.
AB  - The last decade has seen tremendous progress in determining the nature of the
      neurotransmitters which regulate central nervous system pathways involved in the
      regulation of blood pressure. Investigations are now pursuing the identity and
      functional importance of neurotransmitters contained within pathways shown to be
      important in cardiovascular regulation. In addition, several key components of
      the brain stem networks involved in the control of sympathetic activity have been
      identified. For example, numerous studies indicate the importance of neurons
      located in the rostral ventrolateral medulla in the regulation of SPN. Indeed,
      this area contains medullospinal sympathoexcitatory neurons which represent the
      final site of integration of many brain stem and reflex pathways involved in the
      regulation of sympathetic nerve activity. The neurotransmitter which is utilized
      by this medullospinal pathway remains unknown. Epinephrine, substance P and
      glutamate have all been hypothesized as primary chemical mediators in the
      descending pathway from the brain stem to SPN. Interestingly, lesions of, or
      antagonists to, epinephrine, substance P, glutamate and 5-HT neurons all abolish
      sympathetic activity and reduce blood pressure to a level similar to that in a
      spinal animal. Clearly, not all these transmitters are primary mediators of
      sympathetic information carried from the brain stem to the spinal cord. It is
      likely that monoamines and neuropeptides act in the IML, as in other area of the
      central nervous system, as neuromodulators to set the level of excitability of
      SPN rather than relaying sympathetic information over a functionally specific
      medullospinal pathway. This conclusion is supported by the observation that
      midline medullary 5-HT neurons provide a tonic excitatory input to SPN, but
      receive no afferent inputs from other central sympathetic or baroreceptor
      pathways. However, the firing of 5-HT neurons appears to relate to the state of
      vigilance of the animal. This suggests that 5-HT neurons may lower the threshold
      of SPN to sympathetic inputs during states of wakefulness. In addition, the time
      course of the norepinephrine-mediated slow EPSPs and IPSPs in SPN is consistent
      with a gain-setting function. By analogy, epinephrine is likely to act as a
      neuromodulator in the IML rather than to serve as the primary mediator of
      sympathetic information descending from the rostral ventrolateral
      medulla.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1981286
TI  - Second European Symposium on Stone Disease. Basle, 22-24 March, 1990.

PMID- 1981287
TI  - Laser lithotripsy of ureteral calculi.

PMID- 1981288
TI  - [Laser lithotripsy with the neodymium YAG laser].
AB  - Laser-induced shock wave lithotripsy (LISL) with a Q-switched neodymium-YAG laser
      depends on the generation of a laser-induced breakdown in the fluid surrounding
      the stone. An oscillating plasma bubble is created, directing shock waves towards
      the stone. These cavitational effects fragment the calculus into small particles.
      A new bifunctional laser is introduced: this allows both nanosecond pulses for
      shock wave generation and disintegration of urinary calculi and millisecond
      pulses for biliary stones and tissue coagulation. It can be supplied with 320-,
      400-, and 600-micron fibers. We have treated 189 ureteric stones in 185 patients
      with laser lithotripsy utilizing flexible ureteroscopes (n = 26) or rigid
      ureteroscopes (n = 159). It proved possible to fragment 179 stones into small
      pieces. In eight patients LISL was not successful. A rigid cystoscope that can be
      dismantled into an upper and lower hemisheath for the introduction of flexible
      endoscopes into the ureter without prior dilatation of the ureteral orifice was
      used in 15 patients.

PMID- 1981290
TI  - [Laser lithotripsy with automatic shut-off on tissue contact].
AB  - A group of 88 patients with 89 ureteral calculi were treated with the pulsed dye
      laser. Visual control was carried out through 8.5-F or 9.5-F ureteroscopes. The
      laser has automatic shut-off via spectrum analysis of back-scatter laser light.
      Effective laser pulses can therefore only be induced in the case of contact with
      the stone. Of the 89 stones 58 (65.2%) were completely fragmented by laser
      lithotripsy, 15 (16.8%) by laser lithotripsy in combination with ESWL and 9
      (10.1%) by other ureteroscopic techniques. Ureterolithotomy was necessary only in
      1 case (1%). There were 5 calculi (5.6%) that were too hard for fragmentation.
      The pulsed dye-laser is a safe and effective treatment modality for ureteral
      calculi that are not accessible for ESWL or in which ESWL has been unsuccessful.
      Further experimental and clinical trials will have to show whether miniature
      probes for electrohydraulic lithotripsy, dye-laser with automatic shut-off, or
      alexandrite laser will be the method of choice for lithotripsy of ureteral
      calculi.

PMID- 1981289
TI  - [Experimental results and initial clinical experiences with the alexandrite laser
      lithotripter].
AB  - Although extracorporeal shock wave lithotripsy has become the standard therapy
      for urolithiasis, there are still indications for endoscopic stone treatment.
      Laser lithotripsy in association with flexible or semirigid "miniscopes" has
      become increasingly important for this form of therapy. So far the Nd: YAG and
      the pulsed dye laser have been used for laser lithotripsy in clinical
      applications. Since each system has its specific drawbacks, the new solid state
      alexandrite laser was developed to combine the advantages of the two existing
      systems. In order to evaluate the lithotriptic potential of the alexandrite
      laser, a stone model and eight human calculi were exposed to the laser in an
      experimental setting. Results with the stone model were comparable to those
      obtained with a reference Nd: YAG system. Adequate destruction was possible in
      all the human calculi except for one monohydrate stone. In the second part of the
      study, bladder and ureteric wall were exposed to the laser in ten female pigs,
      with different numbers of shock waves at various energy levels. While there was a
      relatively high incidence of early changes, late histological specimens 4-5 weeks
      after the exposure did not reveal any significant pathology. There was no
      stricture-formation in the ureter. Finally 12 patients were treated with
      ureteroscopical laser lithotripsy, and 8 of these were evaluatable. All were
      stone free without any additional lithotripsy and did not develop any secondary
      changes in the ureter. The alexandrite laser can therefore be expected to become
      a safe, reliable and cost-effective alternative for endoscopic stone treatment.

PMID- 1981292
TI  - [The surgical realization of optimal timing for undescended testicle].
AB  - An account is given in this paper of surgical indications to cope with
      cryptorchism. Views on timing of surgical action have undergone considerable
      change over the past 35 years, ranging from prepuberty to the second year of age,
      the latter date being considered optimal now. Optimal timing is not kept in
      practice, as may be seen from a regional longitudinal study over 25 years as well
      as from a representative inquiry among 17 centres of paediatric surgery across
      the GDR over the same period of time and from a cross-section analysis of all
      boys operated on for cryptorchism throughout the GDR in 1986. All medical doctors
      serving at infant welfare centres and day nurseries are invited to refer affected
      boys to surgeons at an earlier date. The existing health system for children and
      adolescents is considered to provide good conditions for lowering the average age
      at surgery.

PMID- 1981291
TI  - [Basic program of myocardial infarct after-care].
AB  - The further diagnostics and therapy is performed after classification of the
      patients in groups with different prognosis. The decision, whether or not an
      invasive diagnostics is necessary and which medicaments are prescribed is based
      on the results of non-invasive diagnostic measures. The beta-blockers are the
      most important group of medicaments. Anticoagulants and antiarrhythmic drugs are
      used within limited and defined indication. A broad application of thrombocyte
      aggregation inhibitors seems to be justified according to latest studies. The
      consequent elimination of coronary risk factors has ascertained prognostic
      effects.

PMID- 1981293
TI  - Adrenergic innervation of the ductus deferens in young and aging rats: a morpho
      functional investigation.
AB  - The pattern of adrenergic innervation and the responsiveness to alpha-agonists of
      the epididymal and prostatic portions of the ductus deferens from young and aging
      rats were examined. The histochemical pictures showed that the distribution of
      the adrenergic fibres varies between the 2 ends of the ductus deferens, with a
      greater density in the prostatic portion. Tissues from rats aged 20 months showed
      the same difference in the adrenergic pattern between the 2 portions. Generally,
      the fluorescent bundles from the tissues of senescent animals seemed to be more
      numerous and compact. The functional data appear to be in contrast with the
      morphological observations, because the epididymal tract of young rats showed the
      highest responsiveness to alpha-agonists. An inverse correlation between the
      number of adrenergic fibres and receptor responsiveness is hypothesized.

PMID- 1981294
TI  - Localization of somatostatin-like immunoreactive fibres in the trigeminal
      principal sensory nucleus of the cat.
AB  - The location and distribution of nerve fibres and terminals displaying
      somatostatin-(SOM)-like immunoreactivity (LI) has been examined in cat trigeminal
      principal sensory nucleus (Vp) using the peroxidase-antiperoxidase technique. The
      varicose SOM-LI nerve fibres form a fine network in the Vp. SOM-positive
      terminals are distributed throughout Vp but they are particularly abundant in the
      ventral subdivision of the nucleus (Vpv). The labelled terminals make
      predominantly asymmetric axodendritic synaptic contacts. SOM-LI terminals only
      rarely form symmetrical synapses with non-reactive neuronal elements and are also
      present free in the neuropil. No SOM-LI perikarya are detected in the Vp. The
      results of the present study suggest that the majority, if not all, of SOM-LI
      fibres in the Vp are probably of primary afferent origin and may be involved in
      relaying trigeminal sensation to neuron located in this brain area.

PMID- 1981295
TI  - A statistical trial of subclassification for tardive dyskinesia.
AB  - The authors applied a statistical method to subclassify tardive dyskinesia (TD)
      in 71 psychiatric patients. Based on two-step statistical procedures and findings
      reported previously, TD is considered to consist of 2 subgroups: a classical
      dyskinesic group and a dystonic group. Symptoms manifested in the former group
      are seen most frequently in the oral region while the latter group, which is
      usually called tardive dystonia, is manifested by movement disorders in the trunk
      and extremities, predominantly. Abnormal movements occurring in the facial region
      characterize a population whose members may belong to either group.

PMID- 1981296
TI  - Predicting neuroleptic response from a combination of multilevel variables in
      acute schizophrenic patients.
AB  - A predetermined set of 22 sociodemographic, psychosocial, clinical,
      neurocognitive and biochemical potential predictor variables was tested in 98
      schizophrenic patients admitted for relapse. The patients were treated with
      neuroleptics, mostly with haloperidol, for 28 d. Ten of the 22 variables
      correlated significantly with the neuroleptic response. Using stepwise multiple
      regression analyses, an optimal combination of 5 predictors was found to be in
      hierarchical order: disturbances of premorbid adjustment, intensity of positive
      symptoms at admission, family history of schizophrenia, working ability during
      the year before admission and serum dopamine-beta-hydroxylase. The 5 best
      predictors explained 29% of outcome variance, and all 22 variables together
      explained 35%. Such neurological characteristics as neurological soft signs,
      handedness, abnormal voluntary movements, spontaneous blink rate and cognitive
      impairment did not predict the treatment response. Several psychopathological,
      psychosocial and clinical predictors known from the literature could also be
      confirmed by cross-validation.

PMID- 1981297
TI  - Clinical characteristics of the Pisa syndrome.
AB  - The Pisa syndrome is not yet well characterized, although there have been
      increasing reports on its prevalence and the clinical features of drug-induced
      dystonia. In this report, we present 20 cases of the Pisa syndrome and discuss
      the clinical symptoms compared with those of classical types of drug-induced
      dystonia. The Pisa syndrome may occur not only as a subtype of acute dystonia but
      also as a subtype of tardive dystonia. Abnormal findings on brain CT were noted
      in both acute and tardive types of the Pisa syndrome, indicating that, like
      tardive dystonia, the Pisa syndrome may be associated with cerebral lesions.
      Young female patients were susceptible to both acute and tardive types of the
      Pisa syndrome, but the prevalence of both types of dystonia was inconsistent in
      these patients. Thus, it seems likely that very complicated pathophysiological
      changes in the brain are involved in the development of the Pisa syndrome.

PMID- 1981298
TI  - [Biological bases of obsessive-compulsive disorder].
AB  - Obsessive Compulsive Disorder, combines several characteristics which suggest an
      organic etiopathology. The evidence relies on: genetic studies; the treatment
      response to drugs with serotonergic profile; the appearance of obsessive
      compulsive disorder after cerebral nervous system damages; the existence of
      neurophysiological alterations; good response to neurosurgery and negative course
      evaluation. In spite of all, the studies of the biological bases of the Obsessive
      compulsive Disorder are scarce, which perhaps can be explained due to its
      relatively low incidence. The present paper reviews all available studies in this
      area, those referred to family predisposition, dysfunctions of neurotransmission
      systems, specific biological markers or those common to depression and the most
      recent research (including new brain imaging techniques) on organic etiology of
      this disorder.

PMID- 1981299
TI  - [The delusion of lycanthropic transformation].
AB  - The authors describe one case of Lycanthropy and revise the literature about this
      theme. They observe that Lycanthropy has received scant attention in the modern
      literature, but appears to have survived into modern times. In some cases the
      patient (as a Delusion) has the belief that he has been transformed into an
      animal. In other cases there appears only what seems to be behaviour of an
      animal. About the first group, the authors make a phenomenological analysis and
      present a clinical case of Lycanthropic delusion.

PMID- 1981300
TI  - GABA and benzodiazepine receptor subtypes. Molecular biology, pharmacology, and
      clinical aspects. Proceedings of the 6th Capo Boi Conference on Neuroscience.
      Villasimius, Italy, June 1989.

PMID- 1981301
TI  - GABAA and GABAB receptor pharmacology in cultured spinal cord neurons.

PMID- 1981302
TI  - Chronic benzodiazepine administration: effects in vivo and in vitro.
AB  - Chronic benzodiazepine administration is associated with neurochemical
      alterations in the GABAergic system, as determined in a variety of animal models
      and tissue culture systems. In animals, effects of chronic benzodiazepine
      agonists on receptor binding are uncertain, but several studies indicate a
      decrease in GABA-dependent chloride uptake. In contrast, limited data indicate
      that chloride uptake is increased after chronic antagonist administration, and
      results of inverse agonist administration are uncertain. Most animal studies are
      limited by lack of attention to drug choice and to pharmacokinetic variables, and
      by failure to determined delivered drug concentrations. More limited data in
      tissue culture systems are conflicting with regard to effects on benzodiazepine
      binding, but recent studies indicate that GABA-dependent chloride uptake may be
      decreased after chronic agonist exposure, and increased after chronic antagonist
      and inverse agonist administration. Data from these systems may complement
      results obtained in intact animals, and cultures may allow more detailed
      examination of the kinetics and specificity of drug effects.

PMID- 1981303
TI  - "Spare receptors" and "partial agonists"--romantic terms to explain a
      pharmacology deriving from the structural diversity of GABAA receptors.

PMID- 1981304
TI  - Zolpidem and alpidem: two imidazopyridines with selectivity for omega 1- and
      omega 3-receptor subtypes.

PMID- 1981305
TI  - The differences in the pharmacological profiles of various benzodiazepine
      recognition site ligands may be associated with GABAA receptor structural
      diversity.

PMID- 1981306
TI  - Overview. Purinergic mechanisms.
AB  - An overview of the history of studies of the biological actions of extracellular
      ATP is presented. The basis of the subdivision of receptors for purines into P1
      purinoceptors for adenosine and P2-purinoceptors for ATP and ADP are considered,
      as well as the recent proposal for subdivision of the ATP receptors into P2X-,
      P2Y-, P2Z-, and P2T- purinoceptor subtypes. These purinoceptor subtypes are
      discussed with respect to their transduction mechanisms, their distribution, and
      their physiological roles, including their roles in cotransmission and
      neuromodulation.

PMID- 1981307
TI  - ATP as a cotransmitter.

PMID- 1981308
TI  - Purine nucleosides and nucleotides as central nervous system modulators.
      Adenosine as the prototypic paracrine neuroactive substance.

PMID- 1981309
TI  - HLA-DR RFLP distributions in two groups of aboriginal Australians.
AB  - HLA-DR and -DQ typing by restriction fragment length polymorphism (RFLP) in
      Aboriginal Australians from the Kimberleys and from Coen shows a restricted
      number of HLA-DR types in these populations. The polymorphism is essentially
      limited to DR2, DR4, DRw14 and DRw8. The most common DR.DQ RFLP haplotype in
      Aborigines shows a novel arrangement of DR and DQ alleles that has important
      implications for histocompatibility matching if the RFLP patterns reflect
      functional variation in HLA class II molecules.

PMID- 1981310
TI  - Comparative cytotoxicities of a series of ellipticine and olivacine derivatives
      on multidrug resistant cells of human and murine origins.
AB  - The MDR P-glycoprotein has been described as a major factor of multidrug
      resistance. This transmembrane glycoprotein acts like an energy dependent efflux
      pump which possesses a broad specificity. It seems to be acting as a pump
      requiring drug fixation prior to extrusion. With the aim of investigating which
      parameters influence the recognition of drugs by the MDR system, we have
      determined the toxicities of different drugs on human and murine sensitive and
      resistant cell lines. For this purpose we have isolated and characterized a human
      adriamycin-resistant cell line, CEM/Adr, which presents an MDR phenotype. The
      tested drugs were ellipticine and olivacine derivatives which differ through
      discrete lateral chain substitutions. The influence of lateral chain
      lipophilicity and nitrogen quaternarization on drug recognition was studied.
      Small modifications in the chemical structure of the drugs have induced large
      changes in their toxicities and in the cross-resistance levels of the MDR cells
      to the tested compounds. The cross-resistances of the murine and human cells to
      the various compounds were strikingly different. The validity of murine screening
      models in the selection of anti-tumor drugs for human therapy must therefore be
      questioned.

PMID- 1981311
TI  - Fat supplementation to the gestation diet of older sows and its effect on
      maternal and fetal fat metabolism.
AB  - Sows that had had 3 previous litters were fed either a diet with no added fat
      (low fat) which was rich in linoleic acid (56.7% 18:2n-6), or a high fat diet
      containing lard, high in total saturates (28.9%) and oleic acid (37.8% 18:1n-9)
      during gestation. Backfat build-up in the sows on the high fat diet was
      accelerated compared to the low fat group. On day 110 of gestation, fetuses were
      removed. The fat content of the diet had no significant effect on sow weight gain
      during gestation, and the number or body weight of fetuses. Activities of sow
      liver and adipose and fetal liver malic enzyme, glucose-6-phosphate dehydrogenase
      (G-6-P) and acetyl-CoA-carboxylase (ACoABx) were measured. Only fetal liver
      ACoABx and sow adipose G-6-P were significantly affected by the sow's diet.

PMID- 1981312
TI  - [Patient-controlled analgesia in postoperative pain--PCA].

PMID- 1981313
TI  - Protein kinase C and calcium. 85th Conference of the Society for Biological
      Chemistry. Konstanz, September 17th, 1990. Abstracts.

PMID- 1981314
TI  - Modern methods in protein and nucleic acid analysis. 86th Conference of the
      Society for Biological Chemistry. Konstanz, September 18th, 1990. Abstracts.

PMID- 1981315
TI  - Effects of glutamate on the serotonin-induced responses of vestibular neurons.
AB  - The aim of this work was to verify whether and how spontaneous or glutamate(GLU)
      induced enhancements of the neuronal firing rate modified the responsiveness of
      the vestibular neurons to microiontophoretic application of serotonin (5-HT).
      During experiments performed on anaesthetized Wistar rats the responses to 5-HT
      applications were studied in neurons of the lateral vestibular nucleus identified
      by the antidromic activation upon stimulation of the vestibulospinal tract. The
      magnitude (in percent) of the 5-HT induced excitatory responses decreased
      (hyperbolic correlation, r = 0.91) when the background mean firing rate was
      enhanced spontaneously or by long-lasting application of GLU. Even in high
      discharging units, the response never changed its sign. The trend to a depression
      of the response to 5-HT in function of the background discharge was observed when
      either the enhancement of firing occurred spontaneously and it was induced by an
      application of GLU, no significant difference (F-test) being found between the
      two cases. It is concluded that serotoninergic afferents can exert a strong
      control upon the vestibular neurons when the background activity is depressed,
      and only a weak influence when the neuronal firing is enhanced by other
      excitatory afferents. It remains to verify whether the type of interference
      observed between GLU and 5-HT is specific or can be also detected between 5-HT
      and other excitatory neuromediators.

PMID- 1981316
TI  - Alcohol and drug interactions.
AB  - Interactions of ethyl alcohol with various drugs are common. Their consequences
      vary depending on the effects of the drugs concerned, the doses of drugs and
      alcohol given and their mode of administration. Pharmacokinetic interactions
      refer to altered tissue concentrations of alcohol or drugs or both and their
      metabolites which sometimes lead to serious toxic reactions. The kinetic
      interactions take place in the absorption or metabolism of alcohol or the drug,
      whereas significant interactions in their distribution phase are rare.
      Pharmacodynamic interactions refer to the combined actions, even serious ones,
      which primarily take place at the tissue (receptor?) level, with or without an
      important pharmacokinetic component of interaction. Acute substantial doses of
      alcohol given quickly tend to inhibit microsomal drug metabolism and thus enhance
      the effects of drugs. Chronic administration of alcohol usually induces the
      synthesis of cytochrome P-450 isoenzyme P-450 II E1, thus accelerating the
      metabolism of its own and, depending on the circumstances, of various drugs as
      well. Reduced actions of the agents may then ensue. If the (toxic) effect of a
      drug (e.g., paracetamol) depends on the formation of active metabolites acute
      intake of alcohol may, paradoxically, reduce the drug effect, while chronic
      alcohol intake enhances it. Induction of hepatic enzymes by alcohol may affect
      the turnover of endogenous vitamins and hormones, or even produce carcinogenic
      substances.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1981317
TI  - Withdrawal phenomena after atenolol and bopindolol: hormonal changes in normal
      volunteers.
AB  - 1. In order to observe and compare the withdrawal phenomena which follow
      treatment with the beta-adrenoceptor blocking drugs, bopindolol (with partial
      agonist activity PAA) and atenolol (without PAA), two groups of six normal
      volunteers were studied before, during and after 16 days drug administration. 2.
      Measurements of plasma levels of cortisol, prolactin, insulin, noradrenaline,
      adrenaline, glucose and potassium were made during a pre-treatment baseline
      period, on maximum dose and for 21 days after drug withdrawal. Isoprenaline
      infusions were given to determine sensitivity of heart rate responses and
      haemodynamic changes measured in response to physiological manoeuvres. 3.
      Following atenolol withdrawal the results show hormonal evidence of adrenergic
      overactivity in the form of elevation of plasma cortisol, insulin and glucose
      levels. After bopindolol withdrawal there was, in contrast, an overshoot of
      plasma prolactin and a persistent elevation of plasma potassium and adrenaline
      post-isoprenaline. 4. The hormonal changes which follow withdrawal of atenolol
      and bopindolol are associated with haemodynamic changes reported elsewhere
      (Walden et al., 1990). 5. These observations provide confirmatory evidence of a
      post beta-adrenoceptor blockade withdrawal syndrome which differs between the two
      drugs studied and this may reflect the properties of the drugs, in particular the
      PAA of bopindolol.

PMID- 1981318
TI  - Withdrawal phenomena after atenolol and bopindolol: haemodynamic responses in
      healthy volunteers.
AB  - 1. The effect of withdrawal of atenolol and bopindolol administration was studied
      in 12 normal volunteers; six on each drug. 2. Following sub-maximal cycle
      ergometer exercise training six sets of base-line observations were made of heart
      rate (HR) and blood pressure (BP) responses; supine, 60 degrees head-up tilt,
      during graduated isoprenaline infusion and sub-maximal cycle exercise. 3. The
      results show that withdrawal phenomena occur following both drug treatments.
      Atenolol produced a hypersensitivity to isoprenaline and a small overshoot of HR
      in response to physiological manoeuvres. In contrast bopindolol produced a
      prolonged state of reduced sensitivity to isoprenaline and some evidence of
      overshoot of HR with physiological manoeuvres. The differences between the
      responses may be explained by the different properties of the two beta
      adrenoceptor blocking drugs. 4. Some subjects showed clear evidence of overshoot
      of HR and BP on exercise demonstrating that certain individuals may be more prone
      to have withdrawal effects than others. 5. The length of time during which
      withdrawal phenomena can occur is probably longer than has previously been
      realised. 6. Hormonal changes were found in the withdrawal period (Walden et al.,
      1990).

PMID- 1981319
TI  - Effect of UK-52,046, an alpha 1-adrenoceptor antagonist, on baroreflex function
      in man.
AB  - 1. In a placebo controlled study (six healthy male subjects), the effects of UK
      52,046 (0.4 microgram kg-1 i.v.) and prazosin (0.25 mg i.v.) on baroreflex
      function were compared, at doses which produced antagonism to phenylephrine, but
      which had no effect on supine blood pressure. 2. Baroreflex function [delta R-R
      interval ms mm Hg-1 change in SBP] was assessed following increases in systolic
      blood pressure (SBP) with phenylephrine and during the Valsalva manoeuvre. 3. At
      these doses neither UK-52,046 nor prazosin had an effect on supine SBP or heart
      rate; however following prazosin, standing SBPs at 5 s (69.7 +/- 7.6 mm Hg) and
      at 3 min (65.5 +/- 11.7 mm Hg) were less than the respective pre-treatment (P
      less than 0.05) values (96.0 +/- 2.9, 110.3 +/- 6.2 mm Hg) and placebo (82.7 +/-
      5.6, 98.7 +/- 11.1 mm Hg). UK-52,046 had no significant effects on standing SBP
      at 5 s or 3 min. At 5 s, pre- and post-treatment R-R intervals (584 +/- 26, 541
      +/- 27 ms respectively) were not significantly different with prazosin, but at 3
      min the post-treatment R-R interval following prazosin (519 +/- 17 ms) was less
      (P less than 0.05) than the pre-treatment value (658 +/- 36 ms). 4. UK-52,046 had
      no effect on baroreflex sensitivity (12.7 +/- 1.3 ms mm Hg-1) compared with
      placebo (17.9 +/- 2.7 ms mm Hg-1).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1981320
TI  - Tremor and the anti-obesity drug BRL 26830A.
AB  - The thermogenic beta 3-adrenoceptor agonist BRL 26830A has been shown to increase
      weight loss in dieting subjects but tremor was a frequent adverse effect. We have
      investigated the magnitude and nature of this tremor after a single oral dose in
      18 subjects. Two complementary techniques were used to attach the recording
      apparatus to the subjects to give both isotonic and isometric measures of tremor.
      Increases of 84% and 40% respectively were found due to exaggeration of
      physiological tremor presumably mediated through concomitant beta 2-adrenoceptor
      stimulation. The use of beta 3-adrenoceptor agonist drugs in the treatment of
      obesity may increase but the development of an agent without tremor inducing
      properties would be an obvious advantage.

PMID- 1981321
TI  - The effects of beta-adrenoceptor antagonists and levomepromazine on the metabolic
      ratio of debrisoquine.
AB  - The in vivo inhibitory effect of five beta-adrenoceptor antagonists and
      levomepromazine on debrisoquine metabolism was assessed in 37 subjects. The
      debrisoquine phenotyping test was performed before and after 7 days' treatment
      with oxprenolol (40 mg three times daily), propranolol (20 mg three times daily),
      timolol (10 mg twice daily), pindolol (5 mg twice daily), metoprolol (50 mg twice
      daily) or levomepromazine (10 mg daily), each of which was given to six-seven
      subjects. No clear change in the urinary metabolic ratio of debrisoquine/4-OH
      debrisoquine (MR) was seen with any of the single beta-adrenoceptor antagonist
      treatments, but the MR value increased significantly when all beta-adrenoceptor
      blocker treatments were considered together. Debrisoquine metabolism was clearly
      impaired after levomepromazine 10 mg daily for 7 days; the mean MR increased from
      1.24 +/- 1.6 to 4.70 +/- 5.23 (P = 0.018) and the excretion of 4
      hydroxydebrisoquine decreased from 0.92 +/- 0.46 mg to 0.31 +/- 0.19 mg (P =
      0.043). Thus, levomepromazine changes MRs towards those characteristic of
      phenotypically poor metabolizers, but beta-adrenoceptor antagonists at the doses
      examined have only a marginal effect.

PMID- 1981322
TI  - Lithium and the natriuretic response to gludopa, fenoldopam and dopamine.

PMID- 1981324
TI  - Adequacy of peritoneal dialysis. Abstracts of the X Annual Conference on
      Peritoneal Dialysis. Dallas, Texas, February 8-10, 1990.

PMID- 1981323
TI  - Lithium and the renal response to gludopa, fenoldopam and dopamine.

PMID- 1981325
TI  - [Endocrine cells of the small intestine in experimental strangulated intestinal
      obstruction].
AB  - In experiment on 25 cats reproducing small intestinal obstruction it has been
      established that the number of endocrine cells (EC) and the degree of their
      saturation with secretory granules increase in 3 and 6 h after the experiment.
      These indices decrease by 12 and 25 h after the experiment. The results obtained
      enable to reveal the EC participation in acute intestinal obstruction
      pathogenesis and to suppose the influence of released serotonin by paracrine way
      on mucous membrane as well as distant action on peristalsis and blood flow
      through intramural nerve plexus.

PMID- 1981326
TI  - Influence of HLA-DP mismatches on primary MLR responses in unrelated HLA-A, B,
      DR, DQ, Dw identical pairs in allogeneic bone marrow transplantation.
AB  - The success of bone marrow transplantation relies on class I and class II HLA
      identity between donor and recipient but until now the impact of DP mismatches on
      primary mixed lymphocyte reaction (MLR I) responses has not yet been clearly
      established. HLA-DP typing has been performed by a RFLP method on 10 patients and
      their 22 selected potential donors (HLA-A, B, DR, DQ, Dw identical according to
      serological, RFLP and oligotyping methods). HLA-DP-matching was then correlated
      with MLR I responses obtained (1) in 22 HLA-A, B, DR, DQ, Dw identical donor
      recipient pairs (patient series) and (2) in 30 HLA-A, B, DR, DQ, Dw identical
      donors pairs used as the control series. We showed that MLR I responses involving
      patients cells were always lower than those involving control cells (p less than
      0.02 in case of two DP-mismatches and p less than 0.001 in the case of one DP
      mismatch). Moreover, in the control series two or one DP mismatches influenced
      MLR I responses in 91% and 77% of the cases respectively; however, there was a
      greater scatter of response values which could be explained by the degree of
      sequence homology between the DP mismatched alleles. In cases with no DP
      mismatch, no proliferative response was observed. Overall, these results suggest
      that the conventional technical conditions of MLR I do not allow detection of
      mismatches other than the well known HLA specificities.

PMID- 1981327
TI  - Dopaminergic modulation of cholinergic responses in rat medial prefrontal cortex:
      an electrophysiological study.
AB  - The neuromodulatory action of dopamine (DA) on acetylcholine (ACh)-evoked
      responses of prefrontal cortex (PFC) neurones were investigated
      electrophysiologically in rats anaesthetised with a combination of urethane and
      ketamine. Iontophoretic application of ACh-excited prefrontal cortex neurones.
      Concurrent application of DA (5-15 nA) resulted in complex changes in the ACh
      evoked responses: (1) DA depressed spontaneous background discharges (designated
      as noise) proportionally more than the ACh-evoked discharges (designated as input
      signals), thus yielding an enhanced signal/noise ratio. This increase in
      signal/noise ratio by dopamine was reversed by iontophoretic application of the
      Da D2 antagonist sulpiride (20-50 nA). Nevertheless, iontophoretic application of
      D2 agonist quinpirole (5-35 nA) enhanced the ACh-evoked response, but was
      accompanied by some increase in spontaneous discharge, thus yielding no change in
      the signal/noise ratio. (2) DA also increased the signal/noise ratio by inducing
      a net increase of the ACh-evoked response but simultaneously suppressed the
      spontaneous activity of PFC neurones. This effect was more prominent following
      blockade of D1 receptors by SCH23390 (6 mg/kg, i.p.), suggesting that D1
      receptors may normally inhibit D2 receptor function in the PFC. In addition,
      endogenous DA in the PFC did not play a significant part in modifying the ACh
      evoked responses since the modulation of ACh-evoked response by DA or its D1 and
      D2 agonists was similar in both saline control and alpha-methyl-p-tyrosine
      pretreated rats. (3) When ejected with larger iontophoretic current (16-35 nA),
      DA suppressed both the ACh-evoked and spontaneous discharge and this effect was
      mimicked by D1 agonist SKF38393 (5-15 nA). Taken together, these results suggest
      that complex dopaminergic modulation of the cholinergic responses of prefrontal
      cortex neurones are mediated by D1 and D2 receptors. This DA action may have a
      functional role in the cognitive-integrative processes occurring in the
      prefrontal cortex.

PMID- 1981328
TI  - Prolonged electrophysiological maturation of transplanted hippocampal neurons.
AB  - The CA1 region of the rat hippocampal formation was lesioned by transient
      forebrain ischemia and subsequently repopulated with dispersed fetal hippocampal
      neurons. Using the hippocampal slice preparation, 7-12 months post
      transplantation, intracellular recordings were made during synaptic activation
      and extracellular calcium measurements were made during iontophoretic application
      of excitatory amino acids. The data indicate that the developmental period of the
      transplanted neurons is prolonged with respect to N-methyl-D-aspartate (NMDA)
      receptor-mediated responses and may be involved in maintaining calcium dependent
      developmental processes such as fiber outgrowth.

PMID- 1981329
TI  - Dendritic action potentials activated by NMDA receptor-mediated EPSPs in CA1
      hippocampal pyramidal cells.
AB  - Intradendritic recordings were obtained in rat CA1 hippocampal pyramidal cells.
      Repetitive stimulation produced substantial short-term potentiation of the
      dendritic excitatory postsynaptic potential (EPSP) which was partly attributable
      to activation of n-methyl-D-aspartate receptors. Accompanying the potentiated
      synaptic response were Na(+)-mediated spikes which appeared to originate at
      multiple sites in the dendritic arbor. These discrete dendritic action potentials
      are rarely distinguishable in somatic recordings, but may contribute to the
      subthreshold response at the pyramidal cell body. In addition, dendritic spikes
      may interact with other voltage-dependent dendritic conductances.

PMID- 1981330
TI  - Spinal cholinergic and monoaminergic receptors mediate descending inhibition from
      the nuclei reticularis gigantocellularis and gigantocellularis pars alpha in the
      rat.
AB  - Focal electrical stimulation and glutamate microinjection in the nuclei
      reticularis gigantocellularis (NGC) and gigantocellularis pars alpha (NGC alpha)
      both inhibit the nociceptive tail-flick (TF) reflex in rats. The present
      experiments were undertaken to determine the transmitter(s) at the level of the
      lumbar spinal cord mediating descending inhibition of the TF reflex produced by
      activation of the NGC/NGC alpha. Intrathecal administration of atropine (7.2-57.6
      nmol) produced a dose-dependent increase in the electrical stimulation threshold
      required for inhibition of the TF reflex. Phentolamine (47.2 or 94.4 nmol) and
      methysergide (32 or 64 nmol) also increased the stimulation threshold
      significantly, but only at the greater doses. Neither naloxone (27.5 or 55 nmol)
      nor mecamylamine (49.1 or 98.2 nmol) affected stimulation thresholds for
      inhibition of the TF reflex. Stimulation at threshold intensities for inhibition
      did not change the blood pressure significantly at most sites of stimulation in
      the NGC/NGC alpha (25/39). Intrathecal administration of atropine, phentolamine
      or methysergide did not affect resting blood pressure or changes associated with
      stimulation in most cases, although inhibition of the TF reflex by stimulation in
      the NGC/NGC alpha was affected consistently by these pretreatments. Similarly,
      glutamate (100 nmol, 0.5 microliter/1.5 min) microinjection produced a short
      lasting inhibition (4.63 +/- 0.70 min, n = 19) of the TF reflex. Glutamate
      microinjection produced both pressor and depressor effects which were not
      affected by intrathecal pretreatment. Inhibition of the TF reflex by glutamate
      was attenuated significantly by intrathecal pretreatment with atropine,
      scopolamine, phentolamine and methysergide, but not naloxone or mecamylamine.
      These findings suggest that either a descending or local spinal cholinergic
      system, together with descending serotonergic and noradrenergic systems, are
      involved in the centrifugal inhibition of spinal nociceptive transmission from
      the NGC/NGC alpha.

PMID- 1981331
TI  - A new chromogen for use in HRP-tract tracing and double-label
      immunocytochemistry.
AB  - A new chromogen, Indophane Blue (IB) was tested for use in HRP-tract tracing and
      double-label immunocytochemistry. Although TMB was slightly more sensitive and
      delineated individual labeled fibers better than IB in tract-tracing experiments,
      there were two advantages to using IB over TMB. First, the IB reaction could be
      performed at a pH of 6.0, rather than the pH of 3.3 required for TMB, resulting
      in much better preservation of tissue. Second, there was no crystalline artifact
      as has been observed with TMB. In the double-label immunocytochemistry
      experiments, the combination of diaminobenzidine for the first chromogen and IB
      as the second, provided excellent contrast.

PMID- 1981332
TI  - Lumbar cerebrospinal fluid concentrations of somatostatin and neuropeptide Y in
      multiple sclerosis.
AB  - The cerebrospinal fluid (CSF) concentrations of somatostatin and neuropeptide Y
      were investigated by use of radioimmunoassay in patients suffering from chronic
      progressive multiple sclerosis. The somatostatin level was significantly
      decreased in the CSF of patients with multiple sclerosis compared to the control
      group. The magnitude of this change was more pronounced in patients with severe
      clinical symptoms of the illness. The CSF neuropeptide Y concentration did not
      differ from the control values. These findings suggest a selective involvement of
      somatostatin neurotransmission in multiple sclerosis.

PMID- 1981334
TI  - Proceedings of the First International Conference on Cytokines and Cell Motility.
      New York City, May 24, 1990.

PMID- 1981333
TI  - Chromosomal translocation t(1;22) and sis oncogene variant with gene
      amplification in a case of atypical malignant lymphoma.
AB  - sis Oncogene amplification and PstI restriction enzyme variant were found in a
      patient of atypical malignant lymphoma with chromosomal translocation t(1;22). A
      diagnosis of atypical malignant lymphoma was made because dual rearrangements of
      both beta chain of T-cell receptor gene and heavy and kappa chains of
      immunoglobulin genes were observed by DNA analysis extracted from the lymph node.
      Amplification of sis was estimated to be about fivefold by dot blot. BamHI and
      EcoRI digested DNA hybridized with sis probe from blood and lymph nodes revealed
      identical bands. Lymph node DNA digested with PstI showed an extra band when
      compared with DNA samples extracted from peripheral blood. Other oncogenes, such
      as myb, abl, and myc showed no variant or amplification. These findings suggest
      that sis is abnormally rearranged in this lymphoma. One possible role of genes on
      chromosome 22, including sis oncogene, in the pathogenesis of this atypical
      malignant lymphoma is discussed.

PMID- 1981335
TI  - [Asthma, bronchial hyperreactivity, neuropeptides].

PMID- 1981336
TI  - [The role of neuropeptides in asthma].

PMID- 1981337
TI  - Seasonal variations in the content of catecholamines in carp heart (Cyprinus
      carpio).
AB  - 1. Seasonal changes in epinephrine and norepinephrine contents were demonstrated
      in ventricular muscle tissues of carp heart. 2. Patterns of changes in
      epinephrine and norepinephrine contents were similar; high during late spring-to
      summer and low in winter; however, the fluctuation in epinephrine content was
      greater than that of norepinephrine. 3. Tyramine caused a positive inotropic
      effect in isolated electrically-stimulated ventricular muscles of carp heart. The
      inotropic effect was totally blocked by reserpine, reduced by propranolol, but
      not altered by atenolol. 4. These results suggest that the catecholamines
      released from sympathetic nerve terminals may contribute to the regulation of the
      seasonal change in the function of cardiac muscles in the carp.

PMID- 1981338
TI  - The effect of thermal acclimation on the activity of arylhydrocarbon hydroxylase
      in rainbow trout (Oncorhynchus mykiss).
AB  - 1. The possibility that temperature acclimation (to 10 or 18 degrees C for 28
      days) would alter the cytochromes P-450 of rainbow trout was addressed. 2. The
      specific content of LM4b (P-450 IA1), the trout isozyme responsible for
      activation of polynuclear aromatic hydrocarbons, was lower in 18 degrees C fish
      than it was in 10 degrees C fish. 3. Kinetic analysis of aryl hydrocarbon
      hydroxylase indicated that, while thermal acclimation caused no change in Vmax,
      it lowered the apparent Km of this enzyme for benzo[a]pyrene when assayed at
      acutely shifted temperatures. 4. Thermal acclimation of fish may have
      significance when feral populations are subjected to acute temperature shifts.

PMID- 1981339
TI  - Effects of some autonomic drugs and neuropeptides on the mechanical activity of
      longitudinal and circular muscle strips isolated from the carp intestinal bulb
      (Cyprinus carpio).
AB  - 1. The mechanical responses to some autonomic drugs and neuropeptides of
      longitudinal muscle (LM) and circular muscle (CM) strips isolated from the carp
      intestinal bulb were investigated in vitro. 2. Acetylcholine and carbamylcholine
      caused concentration-dependent transient contraction of both LM and CM strips.
      Tetrodotoxin had no effect, but atropine selectively decreased the contractile
      responses to acetylcholine and carbamylcholine. 3. Excitatory alpha-2 and
      inhibitory beta adrenoceptors were present in both LM and CM strips. 4. 5
      Hydroxytryptamine (5-HT) caused concentration-dependent contraction of both LM
      and CM strips. Tetrodotoxin, atropine and methysergide decreased the contractile
      responses to 5-HT. 5. Some neuropeptides (angiotensin I, angiotensin II,
      bombesin, bradykinin, neurotensin, somatostatin and vasoactive intestinal
      polypeptide) did not cause any mechanical response (contraction or relaxation) in
      either smooth muscle strip. 6. Substance P (SP), neurokinin A (NKA) and
      neurokinin B (NKB) caused contraction of both LM and CM strips. However, the time
      course of the contraction in LM was different from that in CM. The order of
      potency was NKA greater than SP greater than NKB in LM strips and NKA greater
      than SP much greater than NKB in CM strips. In LM strips, the contractile
      responses to tachykinins were unaffected by spantide and methysergide, but partly
      decreased by tetrodotoxin and atropine. On the other hand, the contractile
      responses of CM strips were unaffected by tetrodotoxin, atropine, methysergide
      and spantide. 7. Dynorphin (1-13) (DYN), leucine-enkephalin (L-Enk) and
      methionine-enkephalin (M-Enk) caused concentration-dependent contraction of both
      LM and CM strips. The order of potency was DYN greater than M-Enk greater than L
      Enk. Naloxone selectively decreased the responses to opiate peptides. 8. The
      present results indicate that acetylcholine, carbamylcholine, catecholamines, 5
      HT, tachykinins (SP, NKA and NKB) and opiate peptides (DYN, L-Enk and M-Enk)
      affect the mechanical activity of LM and CM strips isolated from the carp
      intestinal bulb through their specific receptors.

PMID- 1981340
TI  - Effect of insulin and adrenergic agonists on glucose transport of porcine
      adipocytes.
AB  - 1. Insulin increased basal 2-deoxyglucose uptake in isolated swine adipocytes by
      75%. In the absence of insulin, isoproterenol did not inhibit basal 2
      deoxyglucose transport. 2. Adenosine deaminase plus isoproterenol or theophylline
      alone reduced insulin effect by 10 and 40%, respectively. Isoproterenol alone or
      with 2-chloroadenosine did not inhibit insulin effect on glucose transport
      activity. 3. Insulin effect was inhibited by isoproterenol in the presence of
      theophylline but not in the presence of adenosine deaminase. 4. These results
      suggest that catecholamines do not counter-regulate basal and insulin-stimulated
      glucose transport in swine adipocytes.

PMID- 1981341
TI  - Serum chemistries of Coturnix coturnix japonica given dietary manganese oxide
      (Mn3O4).
AB  - 1. Plasma creatinine and inorganic phosphorus were increased in manganese oxide
      (Mn3O4)-treated adult male Coturnix quail, but BUN, BUN/creatinine ratio, uric
      acid, and total calcium were decreased. 2. Serum enzymes (alkaline phosphatase,
      glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and lactic
      dehydrogenase) were elevated in Mn3O4-treated adult male Coturnix quail, but
      creatine phosphokinase was not affected. 3. Dietary Mn3O4 at 5000 ppm did not
      produce overt signs of toxicosis.

PMID- 1981342
TI  - Hemolytic potency and phospholipase activity of some bee and wasp venoms.
AB  - 1. The action of crude venoms of four aculeate species: Apis mellifera, Vespa
      crabro, Vespula germanica and Vespula vulgaris on human erythrocytes was
      investigated in order to determine the lytic and phospholipase activity of
      different aculeate venoms and their ability to induce red blood cell hemolysis.
      2. Bee venom was the only extract to completely lyse red blood cells at the
      concentration of 2-3 micrograms/ml. 3. Phospholipase activity in all of the
      examined vespid venoms was similar and the highest value was recorded in V.
      germanica. 4. Vespid venoms exhibited phospholipase B activity, which is lacking
      in honeybee venom. 5. In all membrane phospholipids but lecithin,
      lysophospholipase activity of vespid venoms was 2-6 times lower than the relevant
      phospholipase activity. 6. The incubation of red blood cells with purified bee
      venom phospholipase A2 was not accompanied by lysis and, when supplemented with
      purified melittin, the increase of red blood cell lysis was approximately 30%.

PMID- 1981343
TI  - Movements of the large intestine in the anuran larvae, Xenopus laevis.
AB  - 1. The contractile behavior of the large intestine of Xenopus laevis tadpoles was
      studied. 2. The large intestine is divided into a colon and rectum, and shows
      three types of movements: rhythmic ascending (antiperistaltic) waves of
      contraction originating at the anal end of the large bowel, rhythmic longitudinal
      contractions in the rectum and colon, and irregular contractions. The first two
      patterns occur in the large bowel in situ and thus appear mature. The last one
      occurred only in older preparations, and thus appeared pathological. 3.
      Antiperistaltic waves of contractions and longitudinal contractions are generated
      independent of each other, suggesting that circular muscles and longitudinal
      muscles contract separately. 4. Acetylcholine, adrenaline and noradrenaline
      augment motility. 5. The premetamorphic motility of the large bowel is similar to
      that seen in adult frogs. Comparable motility was not observed elsewhere in the
      larval alimentary tract. The large intestine appears to be the first portion of
      the anuran alimentary tract to acquire the adult physiological and morphological
      profile.

PMID- 1981344
TI  - Differential modulation of mouse brain biogenic amines by haloperidol and
      pimozide: implications in Tourette's syndrome.
AB  - 1. A comparison between the effect of equal dose regimens of Tourette's
      medications on mouse motor activity and regional brain monoamines suggests
      differential responses which may underlie drug-induced side-effects. 2.
      Haloperidol was more potent than pimozide in altering striatal dopamine
      concentration which may account for the greater incidence of haloperidol-induced
      extrapyramidal disorders compared to pimozide. 3. Pimozide, but not the
      haloperidol treatment, altered brain serotonin concentrations to suggest a
      decrease in turnover rate which may underlie pimozide-caused sedation in
      Tourette's syndrome. 4. Pimozide was more potent than haloperidol in duration of
      behavioral depression which suggests differential dopamine receptor subtypes
      blockade. 5. Pimozide was more potent than haloperidol in altering 3 of the 6
      brain regions content of norepinephrine-derived normetanephrine which may be
      responsible for the increase in blood pressure reported during pimozide
      treatment.

PMID- 1981345
TI  - Actions of carbaryl on the ionic transport across the isolated skin of Rana
      esculenta.
AB  - 1. Carbaryl, a carbamate used as a pesticide, increases the short-circuit current
      (SCC) across the isolated frog skin in a dose-dependent manner. 2. This effect is
      due to the stimulation of sodium absorption and chloride secretion. 3. Carbaryl
      action on short-circuit current is unrelated to its inhibitory power on
      cholinesterase; this statement is supported by two experimental results: (a)
      carbaryl is equally active on both sides of the skin, (b) atropine pretreatment
      does not inhibit the carbaryl action on SCC.

PMID- 1981346
TI  - Characterization of the muscarinic cholinergic receptor in the opossum (Didelphis
      virginiana, Kerr) submandibular gland: differences in receptor density and
      subtype compared with higher mammalian species.
AB  - 1. Kinetic, saturation and inhibition radioligand binding experiments with [3H]-N
      methylscopolamine and [3H]quinuclidinyl benzilate were used to characterize the
      muscarinic cholinergic receptor in opossum (Didelphis virginiana, Kerr)
      submandibular salivary gland membranes. 2. The receptor density in opossum
      submandibular gland was found to be more than 3-fold higher than in rat, and 22
      fold higher than in human, submandibular glands. 3. Inhibitor equilibrium
      dissociation constants for the antagonists pirenzepine, dicyclomine, atropine, N
      methylscopolamine and AF-DX 116 revealed that the muscarinic receptor present in
      opossum submandibular gland appears to be the M1 subtype rather than the M3
      subtype found in human and rat.

PMID- 1981347
TI  - Ca2(+)-mobilizing receptors of gastrulating chick embryo.
AB  - 1. Gastrulating chick embryo cells (stages 3-5 by HH) possess Ca2(+)-mobilizing
      receptors for ACh and ATP; insulin and noradrenaline have a weaker effect on
      [Ca2+]i mobilization. 2. The ED50 value for ACh is 4 (+/- 0.5) X 10(-6) M and for
      ATP 20 (+/- 5) X 10(-6) M. 3. Addition of ACh and ATP to dissociated chick embryo
      cells causes rapid accumulation of IP3. 4. The stimulatory effects of ACh and ATP
      on [Ca2+]i mobilization and IP3 rapid formation are both additive.

PMID- 1981349
TI  - A comparative study of the biological properties of Australian elapid venoms.
AB  - 1. The hemorrhagic, procoagulant, anticoagulant, protease, phosphodiesterase,
      alkaline phosphomonoesterase, L-amino acid oxidase, acetylcholinesterase,
      arginine ester hydrolase, phospholipase A, 5'-nucleotidase and hyaluronidase
      activities of 39 samples of venoms from 13 species (15 taxa) of Australian
      elapids were determined and the Sephadex G-75 gel filtration patterns for some of
      the venoms were also examined. 2. The results indicate that Australian elapid
      venoms can be divided into two groups: procoagulant Australian venoms (including
      N. scutatus, N. ater, O. scutellatus, O. microlepidotus, P. porphyriacus, T.
      carinatus, H. stephensii and P. textilis) and non-procoagulant Australian venoms
      (including A. superbus, P. colletti, P. australis, P. guttatus and A.
      antarcticus). 3. The non-procoagulant Australian venoms exhibited biological
      properties similar to other elapid venoms, while the procoagulant Australian
      venoms exhibited some properties characteristic of viperid venoms. 4. The data
      show that information on venom biological properties can be used for
      differentiation of many species of Australian elapids. 5. Particularly useful for
      this purpose are the hyaluronidase, alkaline phosphomonoesterase,
      acetylcholinesterase, and the procoagulant activities and the Sephadex G-75 gel
      filtration patterns of the venoms.

PMID- 1981350
TI  - The 3rd symposium on portal hypertension.

PMID- 1981348
TI  - Comparative studies on the effects of some enkephalin agonists on the ERG of frog
      and turtle.
AB  - 1. Effects of mu-agonist morphine in a concentration of 1.10(-5)-1.10(-6) M and
      delta-agonist Dalargin in a concentration of 1.10(-5)-1.10(-8) M on
      electroretinogram (ERG) of frog (mixed type of retina) and turtle (predominantly
      cone retina) were investigated. 2. The enkephalin agonists studied influenced
      both types of retina in a different manner, producing mainly inhibitory effects.
      3. Variability in mu-receptors sensitivity in the turtle retina, most probably
      depending on the seasons, was observed. 4. The data obtained show that opiate
      sensitive mechanisms control the bioelectric activity of the distal layers of
      frog and turtle retina. 5. Species specificity and variability in sensitivity of
      the opiate receptors are discussed.

PMID- 1981351
TI  - Symposium on Steroids and Neuronal Activity. London, 23-25 January 1990.

PMID- 1981352
TI  - Steroid effects on neuronal activity: when is the genome involved?
AB  - For over four decades steroids have been regarded first as facilitators of
      enzymic reactions and subsequently as activators of genomic activity. The brain,
      long studied in terms of its bioelectric properties and anatomical connectivity,
      has now been recognized as a complex target tissue for genomic effects of steroid
      hormones, which bring about long-lasting alterations in brain structure and
      neurochemistry as well as changes in behaviour and neuroendocrine function.
      Studies of steroid effects on brain bioelectric activity have also shown rapid
      effects which are difficult to explain by a strictly genomic mechanism. One way
      to distinguish between genomic and non-genomic effects is by the time course,
      with extremely rapid effects being non-genomic and delayed effects being genomic.
      Effects with onset latencies of minutes to an hour may be due to either
      mechanism. Examples illustrating genomic actions include delayed effects of
      oestrogen which alter oxytocin and GABAA receptors and induce spines on dendrites
      and delayed glucocorticoid effects on neuronal survival. There are also examples
      of apparent genomic effects of oestradiol which interact with rapid and
      apparently non-genomic effects of progesterone: progesterone rapidly promotes
      spread of oestrogen-induced oxytocin receptors in ventromedial hypothalamus and
      rapidly modifies oestrogen-regulated GABAA receptor density in hypothalamus. The
      former effect is one produced by progesterone itself whereas the latter effect
      may be related to the ability of progesterone metabolites to interact with the
      chloride channel of the GABAA-benzodiazepine receptor complex.

PMID- 1981353
TI  - Beta-agonists and asthma mortality. What have we learned, what questions remain?

PMID- 1981354
TI  - Cetirizine. A review of its pharmacological properties and clinical potential in
      allergic rhinitis, pollen-induced asthma, and chronic urticaria.
AB  - Cetirizine, a piperazine derivative and carboxylated metabolite of hydroxyzine,
      is a potent histamine H1-receptor antagonist with antiallergic properties. It has
      marked affinity for peripheral histamine H1-receptors and, at the standard dose
      of 10mg daily, lacks the CNS depressant effects of standard antihistamines. In
      addition, it inhibits histamine release and eosinophil chemotaxis during the
      secondary phase of the allergic response. Results from controlled clinical trials
      indicate that cetirizine is an effective and well tolerated treatment of seasonal
      and perennial allergic rhinitis and chronic idiopathic urticaria. Cetirizine
      appears to be as effective as conventional dosages of terfenadine,
      chlorpheniramine and hydroxyzine in relieving symptoms associated with these
      disorders and produces a markedly lower incidence of sedation than
      chlorpheniramine, hydroxyzine and several other standard antihistamines. Thus,
      cetirizine appears to provide a useful alternative to other 'nonsedating'
      antihistamines; cetirizine may also have a future role in the treatment of
      allergic asthma and certain forms of physical urticaria.

PMID- 1981355
TI  - The lateral spread of ictal discharges in neocortical brain slices.
AB  - The in vitro brain slice technique was used to examine the lateral propagation of
      spontaneous electrographic ictal episodes across adjacent areas of guinea pig
      neocortex. Epileptiform activity was induced by perfusing slices with Mg-free
      artificial CSF. Simultaneous field potential recordings of ictal episodes were
      obtained from 4 micropipettes placed 1-3 mm apart across coronal slices in middle
      cortical layers. Two types of lateral spread were characterized. Ictal episodes
      often developed focally and then spread as a slowly moving wavefront traveling at
      less than 0.3 mm/sec into adjacent, uninvolved cortex. By contrast, other
      episodes began nearly synchronously at all cortical sites. The individual
      afterdischarges that composed each ictal episode propagated rapidly across the
      cortex at greater than 30 mm/sec and were triggered by multiple pacemakers. Ictal
      episodes always terminated abruptly across the entire slice. The NMDA-receptor
      antagonist, 2-amino-phosphono-valerate, applied focally between recording sites,
      blocked rapid propagation across treated areas and resulted in the emergence of
      spatially separate, independent pacemakers. Pacemaker failure is the proposed
      mechanism for simultaneous and generalized termination of ictal episodes in this
      in vitro model of epileptogenesis.

PMID- 1981356
TI  - Rat ventral mesencephalon grown as organotypic slice cultures and co-cultured
      with striatum, hippocampus, and cerebellum.
AB  - Tissue slices of rat ventral mesencephalon (VM), striatum, hippocampus and
      cerebellum were prepared from late fetal (E21) to 7 day old (P7) rats and
      cultured for 3 to 60 days by the roller tube technique before they were stained
      immunocytochemically for tyrosine hydroxylase (TH), a marker of dopaminergic (DA)
      neurons and fibres. The TH immunoreactive (TH-i), DA neurons retained their
      morphological in vivo characteristics in the VM slice cultures consisting of the
      substantia nigra (SN) and the ventral tegmental area (VTA). The general
      morphology of the described neuronal cell types did not appear to change when the
      VM slices were co-cultured with striatal tissue, a major normal target of the DA
      neurons, but an extensive innervation of the striatum by TH-i nerve fibres was
      observed. In co-cultures of VM and hippocampus, a minor target organ of DA
      fibres, growth of TH-i nerve fibres was observed mainly into the opposing edge of
      the hippocampal slice. In co-cultures of VM and cerebellum, which is normally
      devoid of DA fibres, no significant growth of TH-i nerve fibres into the
      cerebellar slices was observed. Besides suggesting a target orientated growth of
      ventral mesencephalic DA fibres, the results point to the further use of VM slice
      cultures in the study of the developmental, plastic and regenerative properties
      of DA neurons.

PMID- 1981357
TI  - Early lesion of mystacial vibrissae in rats results in an increase of
      somatostatin-labelled cells in the somatosensory cortex.
AB  - Recent studies in the developing cortex have shown that during the first 2
      postnatal weeks somatostatin (SRIF)-containing neurons appear in greater numbers.
      After this time their numbers decline significantly probably due to cell death
      (Cavanagh and Parnavelas 1988). In this study we report changes in the
      distribution of SRIF-labelled cells in the somatosensory cortex of adult rats
      following unilateral lesions of mystacial vibrissae at birth. Specifically, we
      observed that the side contralateral to the lesion contained a significantly
      greater number of labelled cells compared to the ipsilateral side. We suggest
      that the decline in cell numbers observed during normal development is reduced
      following early deafferentation.

PMID- 1981359
TI  - Respiratory muscle fatigue.

PMID- 1981358
TI  - Release of met-enkephalin and its modulation through acetylcholine receptors in
      the rabbit superior colliculus.
AB  - This report presents evidence for the depolarization-dependent release of met
      enkephalin from the superior colliculus of the rabbit. Collicular tissue was
      placed in superfusion chambers and met-enkephalin accumulation in the superfusate
      was measured by radioimmunoassay. Exposure to high potassium concentrations (30
      mM and 56 mM) increased met-enkephalin release. This is the fourth transmitter
      shown to be released from collicular tissue. Furthermore, we have obtained the
      first evidence that suggests that met-enkephalin release is susceptible to
      muscarinic modulation. While the depolarization-dependent release of met
      enkephalin was depressed in the presence of atropine (1 microM), hexamethonium
      (100 microM) did not block the increase of met-enkephalin release induced by high
      potassium.

PMID- 1981360
TI  - From alveoli back to bronchi: new perspectives of bronchoalveolar lavage.

PMID- 1981361
TI  - [Inhibin and activin].

PMID- 1981362
TI  - [Basic and clinical studies of neuropeptide-producing carcinoma].

PMID- 1981363
TI  - Bioavailability of single and multiple doses of enteric-coated mesalamine and
      sulphasalazine.
AB  - The bioavailibity of mesalamine from enteric-coated mesalamine and sulphasalazine
      was determined following a single dose and at steady state in healthy subjects in
      crossover studies. Plasma concentrations and urinary excretion of mesalamine and
      its major metabolite, N-acetyl-5-aminosalicylic acid, were measured. After a
      single dose of enteric-coated mesalamine, about 10 h elapsed before the onset of
      measurable plasma drug concentrations, probably representing gastro-intestinal
      transit prior to drug release near the ileocaecal junction. The elimination
      kinetics were similar for a single oral dose and steady state using enteric
      coated mesalamine, but after both single and multiple administration of enteric
      coated mesalamine only about 20% of the mesalamine given was absorbed, with about
      80% estimated to remain for colon therapeutic activity. It is concluded that,
      despite different mechanisms of mesalamine release, enteric-coated mesalamine and
      sulphasalazine produced similar mesalamine absorption.

PMID- 1981364
TI  - Use of the recombinant human thyrotropin receptor (TSH-R) expressed in mammalian
      cell lines to assay TSH-R autoantibodies.
AB  - We report on two assays for autoantibodies to the TSH-R which have been developed
      using materials from mammalian cells transfected with the cDNA for the human TSH
      R. In the first, a particulate fraction has been prepared from COS cells,
      transiently expressing the human TSH-R and used in a radioreceptor assay in
      conjunction with bovine 125I-TSH. Immunoglobulins (IgGs) from patients with
      Graves' disease (n = 11) and idiopathic myxoedema (n = 2) have been used as
      competitors of 125I-TSH binding to the COS TSH-R membranes and the results have
      been compared with those obtained with a commercially available kit for measuring
      TSH-R autoantibodies, which uses solubilised porcine TSH-R. Both assays showed
      similar performance, being particularly sensitive to antibodies from patients
      with idiopathic myxoedema. In the second assay system we have used a CHO cloned
      cell line (JP26) stably transfected with the human TSH-R. A selection of IgG
      preparations from patients with Graves' disease and of six normal controls was
      used to test the ability of this cell line to detect thyroid stimulating
      immunoglobulins (TSAb) by increasing its cAMP production. The assay was performed
      under two conditions: in standard (isotonic) medium or in hypotonic medium.
      Freshly thawed human thyrocytes incubated in hypotonic medium served as a
      reference method. Only five patients scored positive when tested in the JP26 cell
      line under isotonic conditions. When the assay was performed in a hypotonic
      medium, a significant positive correlation was observed between the results given
      by JP26 cells and human thyrocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1981365
TI  - Differential coupling with pertussis toxin-sensitive G proteins of dopamine and
      somatostatin receptors involved in regulation of adenohypophyseal secretion.
AB  - D2 dopamine receptors and somatostatin receptors in adenohypophyseal cells are
      coupled through G proteins to various transduction mechanisms. To study the
      involvement of these different transduction mechanisms and of various G proteins
      in the dopamine and somatostatin regulation of prolactin (PRL), growth hormone
      (GH) and thyroid-stimulating hormone (TSH) secretions, we have pretreated the
      adenohypophyseal cells in primary culture with increasing doses of pertussis
      toxin. The guanosine triphosphate (GTP) dependency of the negative coupling of
      dopamine and somatostatin receptors with adenylate cyclase in the same membrane
      preparation from anterior pituitary cells was different. In fact, higher GTP
      doses were requested to obtain dopamine inhibition, suggesting that different G
      proteins were involved in the coupling of these two receptors with adenylate
      cyclase. However, the inhibition of adenylate cyclase activity by both
      neurohormones was fully sensitive to pertussis toxin pretreatment with a similar
      IC50 for the toxin. The IC50 for the toxin was also similar for the blockade of
      dopamine or somatostatin inhibition of the three-hormone secretion as well as for
      the stimulation on basal PRL or GH secretion or the reduction of thyrotropin
      releasing hormone (TRH)-stimulated prolactin secretion, suggesting that the toxin
      acts through similar mechanisms on these different phenomena. Pretreatment of the
      cells with Bordetella pertussis toxin differentially affected the effects of both
      neurohormones on the three cell types. A complete reversion of the inhibition of
      secretion was observed only in the case of somatostatin on PRL and TSH cells. In
      contrast, the somatostatin inhibition of GH secretion was only partially reversed
      by the pertussis toxin pretreatment. This was also the case of dopamine
      inhibition of PRL secretion. It can be concluded that: (1) On PRL secretion
      dopamine and somatostatin do not share all the mechanisms since the intensity of
      their inhibition and the reversibility of their effects by pertussis toxin were
      differential. (2) Different mechanisms of action are implicated in the effect of
      somatostatin on PRL, GH and TSH secretions. (3) Different G proteins might be
      involved in the coupling of dopamine and somatostatin receptors with adenylate
      cyclase.

PMID- 1981366
TI  - Expression of HOX homeogenes in human neuroblastoma cell culture lines.
AB  - Mammalian genes containing a class-I homeobox (HOX genes) are highly expressed in
      the embryonic nervous system. As a first step towards the molecular analysis of
      the role these genes play in neural cells, we studied the expression of four
      human HOX genes in five neuroblastoma (NB) cell lines - SK-N-BE, CHP-134, IMR-32,
      SK-N-SH and LAN-1 - during the process of differentiation induced by treatment
      with retinoic acid (RA). The four genes, HOX1D, 2F, 3E and 4B, located at
      corresponding positions in the four HOX loci, share a high degree of sequence
      similarity with the Drosophila Deformed homeotic gene and constitute a homology
      group, group 10. One of these genes, HOX1D, is not expressed in the cells used,
      whereas the other three are highly expressed in untreated and RA-induced NB
      cells, even though the expression pattern in the various lines is slightly
      different for the three genes. Our analysis reveals a complex and specific
      expression pattern in these lines, paving the way to an identification of
      different NB-cell populations by means of specific HOX gene expression schemes.
      On the other hand, in every line studied, morphological maturation toward a
      neuronal differentiated phenotype appears to be associated with increased HOX
      gene expression.

PMID- 1981367
TI  - Immunomodulatory properties of certain amino acids influence the
      immunostimulating properties of specific peptides.
AB  - Using the previously obtained data that amino acids could influence the thymus
      dependent immune response, the significance of amino acids in the
      immunostimulating activity of peptides has been studied. The effect of seven
      synthetic fragments of murine Thy-1 antigen, non-sulfated cholecystokinin (CCK
      8), the two tetrapeptides at the N- and C-terminal fragments of CCK-8, as well as
      neurotensin (NT) have been investigated. It has been found that both NT and those
      Thy-1 fragments which consisted of immunologically inert amino acids, did not
      influence the immune response in mice. CCK-8, its C-terminal fragment and those
      Thy-1-antigen peptides which contained immunoactive amino acids at C- or N
      terminus or both, stimulated IgM-plaque forming cells (PFC) in animals. The N
      terminal CCK-8 tetrapeptide showed negligible activity. The possibility of the
      existence of two independent immunoregulatory systems--one amino acids based and
      the other dependent upon a sequence of amino acids in the peptide is being
      discussed.

PMID- 1981368
TI  - Aldolase DNA polymorphism in subterranean mole-rats: genetic differentiation and
      environmental correlates.
AB  - We analysed the genetic diversity and environmental correlates of the aldolase A
      and B genes by means of restriction endonucleases (DNA RFLP analysis), in the
      four chromosomal species (2n = 52, 54, 58 and 60) of the actively speciating
      subterranean mole-rats of the Spalax ehrenbergi superspecies in Israel. The
      results indicated that: (i) both aldolase genes are highly polymorphic; (ii)
      fragment frequencies and fragment profiles display geographical patterns and
      significant ecological correlates; (iii) discriminant analysis largely succeeded
      in separating the four chromosomal species on the basis of variation of aldolase
      RFLPs.

PMID- 1981369
TI  - Quantitative genetic background effects on the Antennapaedia phenotype in
      Drosophila melanogaster.
AB  - Genetic background variation influencing expression of the Antennapaedia homeotic
      phenotype was examined by crossing the Antp73b allele of the Antennapaedia locus
      reciprocally into seven isogenically derived wild type strains of Drosophila
      melanogaster and their genetically heterogeneous parent strain, Dover. The parent
      Antp73b strain's Antennapaedia phenotype shows a small patch of untransformed
      antennal tissue remaining on the homeotic femur. The size of this patch was used
      as an assay for background variation influencing expression of the Antp73b
      homeotic mutation. Patch size varied approximately six-fold across the different
      genetic backgrounds. Effects of maternal parent, sex, and sex-linkage were also
      observed.

PMID- 1981370
TI  - Cefpodoxime proxetil: a third-generation oral cephalosporin. International
      Congress for Infectious Diseases, Montreal, Canada, 15-19 July 1990.

PMID- 1981371
TI  - Prophylactic H2 receptor antagonists before surgery?

PMID- 1981372
TI  - CD4 cells from patients with autoimmune thyroid disease secrete interferon gamma
      after stimulation by thyroid microsomal antigen; CD8 cells suppress this
      secretion.
AB  - The production of interferon gamma (IFN gamma) by peripheral blood mononuclear
      cells (PBMC) from normal persons and patients with autoimmune thyroid disease
      (AITD) has been studied in vitro either spontaneously or after stimulation with
      thyroid microsomal antigen (TMc) or liver microsomal antigen (LMc). The numbers
      of IFN gamma secreting cells were measured by a spot-ELISA technique. AITD PBMC
      spontaneously contained significantly more IFN gamma secreting cells than did
      normal control PBMC. Moreover, TMc antigen caused a significantly greater number
      of IFN gamma secreting cells in AITD PBMC than did LMc antigen, whereas there was
      no significant difference between the two antigens in the normal control PBMC
      preparations. Thus TMc antigen caused a stimulation of the number of IFN gamma
      secreting cells only in the AITD PBMC and not in the normal PBMC. CD4 plus B
      cells or CD4 cells alone (with monocytes in both instances) contained more IFN
      gamma secreting cells under unstimulated conditions than did CD8 cells in both
      groups. AITD CD4 plus B cells (or CD4 cells) contained more IFN gamma secreting
      cells than did normal cells, but there was no significant difference between both
      groups in terms of the number of CD8 IFN gamma secreting cells. Normal CD4 plus B
      cells (or CD4 cells) responded to TMc antigen significantly more than did total
      normal PBMC at 10 and 1,000 ng/ml TMc. This was not the case when patients' CD4
      plus B cells (or CD4 cells) were compared with patients' total PBMC, in which
      there were no significant differences. This suggests that CD8 suppressor activity
      was inadequate in AITD and thus the deletion of CD8 cells did not result in an
      increase in IFN gamma secreting cells. When TMc antigen was added to AITD CD8
      cells, there was a significant diminution of IFN gamma secreting cell numbers at
      10 and 1,000 ng/ml TMc. Moreover, adding autologous CD8 cells to CD4 plus B cells
      resulted in a significant suppression of IFN gamma production at 100 and 1,000
      ng/ml TMc in both groups. AITD CD8 cells appeared to be somewhat less effective
      than normal CD8 cells, but this did not reach significance. It is thus concluded
      that AITD CD4 cells respond specifically to TMc antigen. CD4 production of IFN
      gamma appears to be suppressed by CD8 cells activated with antigen and the CD8
      cells appear to be involved in the regulation of IFN gamma production by the CD4
      cells.

PMID- 1981373
TI  - Central neuroregulation of hypothalamic corticotropin-releasing hormone (CRH-41)
      secretion.

PMID- 1981374
TI  - Taxus spp. needles contain amounts of taxol comparable to the bark of Taxus
      brevifolia: analysis and isolation.
AB  - New sources for the antitumor natural product taxol [1] are needed as demands for
      this promising cancer chemotherapeutic agent increase. Presently, supplies of
      taxol for clinical studies are obtained from the bark of Taxus brevifolia, a
      potentially limited source. Using analytical methods, the needles and stems of
      six Taxus species have been examined for taxol [1] and 10-deacetylbaccatin III
      [5], a related compound that can be converted to taxol through a semi-synthetic
      route. Amounts of taxol comparable to quantities reported from the bark of T.
      brevifolia were found in the needles of four of the Taxus species investigated.
      In addition, taxol was isolated from the needles of one Taxus species. Thus,
      Taxus needles may provide a renewable source of this valuable compound.

PMID- 1981375
TI  - CSF somatostatin-like immunoreactivity in dementia of Parkinson's disease.

PMID- 1981376
TI  - [Surgical treatment of nonspecific aorto-arteritis].
AB  - The authors analyse experience with 273 operations carried out in 273 patients;
      107 operations were conducted on the branches of the aortic arch, 136 were
      performed for the "middle aorta syndrome", and 30 operations were performed in
      affections of the terminal aorta and the iliac arteries. Experience is also shown
      in operative treatment of 32 patients with coexistent affections of the "middle
      aorta" and the branches of the aortic arch, the surgical tactics and the sequence
      of operations in this type of pathology are discussed. Problems dealing with the
      classification of nonspecific aorto-aortitis (NAA) are discussed, and the
      authors' classification of the variants of the vascular manifestations of the
      process is suggested. The authors draw attention to the need for preoperative
      management of patients with UAA for correcting the activity of the inflammatory
      process. Hemosorption and immunocorrective therapy are suggested for this
      purpose. Means for improving the results of surgical treatment of patients with
      UAA are suggested. The total mortality was 13%.

PMID- 1981377
TI  - [Experience with 303 operations in nonspecific aorto-arteritis (Takayasu
      syndrome)].
AB  - From analysis of his personal 25-year experience the author suggests a
      classification of aorto-arteritis and discusses the incidence of various clinical
      syndromes. Among the 303 operations only 14 were nephrectomies, the remaining
      were reconstructive vascular operations. Most interventions were conducted on the
      branches of the aortic arch (115 operations), renal (112 operations) and visceral
      (73 operations) arteries. In reconstruction of the branches of the aortic arch,
      preference is given to extrathoracic shunting (64 operations), in the absence of
      the necessary conditions a bifurcation carotid or carotid-subclavian shunt from
      the ascending aorta is carried out (42 operations). In reconstruction of the
      thoracoabdominal aorta preference is given to a thoracophrenolumbotomy approach
      suggested by the author and the method of transaortic endarterectomy. The author
      describes a new method for the management of inflammation in patients with
      aortitis by means of cyclophosphamide and methylprednisolone. The good late-term
      results occur due to arrest of the inflammation. The results of the surgical
      methods are much more effective than those of nonoperative therapy alone.

PMID- 1981378
TI  - [Neuropharmacological reactivity of the body exposed to extreme factors: the
      effect of radiation].
AB  - The functional state of neurochemical structures of male mice was investigated
      after their gamma-irradiation with 137Cs (1.9 Gy/min) at a dose of 100 Gy. The
      animals were treated with the following drugs that produce selective effects on
      specific receptors: galanthamine (0.5 mg/kg), amizyl (30 and 60 mg/kg), arpenal
      (30 mg/kg), phenamine (3, 6 and 10 mg/kg) phentolamine and obsidan (1 mg/kg),
      haloperidol (0.5 and 1 mg/kg), apomorphine (2 mg/kg), phenazepam (0.05 and 2
      mg/kg), phenibut (200 mg/kg), and strychnin (0.1 and 0.2 mg/kg). The physical
      performance of the animals was measured with the aid of a swimming test applied 2
      and 6 hours after irradiation. The results point to the development of
      heterologous desensibilization of receptors at early post-irradiation periods.
      The high effectiveness of agonists and antagonists of CNS transmitters in the
      nonirradiated animals and their low effectiveness in the irradiated animals may
      be considered as an indicator of post-radiation injury of specific receptors.
      This seems to be responsible for partial or total resistance of irradiated
      animals to the regulatory effects of neurotransmitters. These
      neuropharmacological interactions may obviously be modified in response to the
      combined effects of space flight factors.

PMID- 1981380
TI  - [Microflora of drinking water reclaimed from waste water in an hermetically
      closed environment].
AB  - Microorganisms dwelling in drinking water reclaimed from water containing water
      in an enclosed environment were identified. The microbial species in the water
      reclaimed from the condensate of hydrogen peroxide decomposition products and
      from the air humidity condensate showed specific features and differences when
      compared to those in natural water.

PMID- 1981379
TI  - [Pharmacological correction of stress reactions after hyperthermia].
AB  - It was demonstrated experimentally that aminazine, phentolamine, nuredal,
      sapilent, teperin, dopegyt improved significantly the health status of animals
      exposed to high temperature and in many cases prevented their death. This gives
      evidence that the sympathetic nervous system plays a leading role in heat stroke
      and that sympathotrophic drugs can be used for protective purpose during acute
      overheating.

PMID- 1981382
TI  - Valproate potentiates and picrotoxin antagonizes the anxiolytic action of ethanol
      in a nonshock conflict task.
AB  - The purpose of this study was to examine the effects of the indirect GABA agonist
      valproate and the indirect GABA antagonist picrotoxin on the anxiolytic (anti
      conflict) activity of ethanol in a behavioral conflict task that does not employ
      electroshock. This task (negative contrast) quantifies how animals respond to an
      abrupt, unexpected reduction in reward. Treatment with valproate alone did not
      elevated depressed behavior engendered by abrupt reduction in reward. However,
      when administered together with a sub-effective dose of ethanol (0.5 g/kg),
      valproate (50-200 mg/kg) dose-dependently potentiated the anxiolytic action of
      ethanol. Picrotoxin (2 mg/kg) antagonized the anxiolytic effects of a larger dose
      of ethanol (1.0 g/kg) given alone, as well as the ability of valproate to enhance
      the anxiolytic effects of smaller dose of ethanol (0.5 g/kg). As such, these data
      support a role for GABA in mediating the anxiolytic activity of ethanol.

PMID- 1981381
TI  - Hantavirus infection in laboratory and wild rodents in Argentina.
AB  - Serum samples from urban and laboratory rats, laboratory mice and wild and
      laboratory cricetids in Argentina were tested by immunofluorescence and plaque
      reduction neutralization tests to investigate prevalence of anti-Hantavirus
      antibodies. A total of 102 sera were obtained from laboratory rodents in 4
      different animal-rooms, 31 from harbor rats and 30 from wild cricetids in 1985
      1987. Anti-Hantavirus antibodies were detected in 22.5% of Rattus norvegicus in 3
      of the animal-rooms but harbor rats were found to be free of Hantavirus
      infection. Previously, the presence of anti-Hantavirus antibodies had been
      demonstrated in the sera obtained from laboratory workers in these same 3 animal
      rooms; it can be concluded that the laboratory rats were the source of this human
      infection. On the contrary, laboratory mice and cricetids failed to show
      Hantavirus infection while the wild vesper mouse Calomys musculinus (the main
      Junin virus reservoir) showed a prevalence of 23.5%. The presence of Hantavirus
      infection is hereby reported for the first time in wild C. musculinus and in
      laboratory R. norvegicus in Argentina.

PMID- 1981383
TI  - [Cytogenetic study of 201 subjects with altered reproductive fitness].
AB  - The A. report a cytogenetic study performed on 201 subjects with a defective
      reproductive fitness. In total, they detected 37 chromosomal changes (18.4%): 7
      in 48 subjects (24 couples) with sterility (14.5%), 11 in 96 with hypogonadism
      and/or criptorchidism (11.4%), 15 in 38 women with oligoamenorrhoea (39.4%) and 4
      in 4 patients with Morris syndrome (100%). On the contrary, no chromosomal change
      was detected in 15 patients with pure gynecomastia. The A. discuss the
      significance of these chromosomal aberrations, and particularly: the mosaicism
      XO/XX, because this chromosome picture may be associated with fertility, as in
      our case; the isodicentric X, because the patient showed the clinical features of
      the Turner's syndrome; the inv(11), because the patient showed a progressive
      oligoamenorrhoea, leading us to retain that some chromosome changes, by
      determining a severe gametic selection, may cause infertility in these subjects.
      the t(13;14), detected in men with azoospermia, because these changes confirm the
      presence of a gametic selection, mostly in men. Therefore, according to other
      reports, the A. suggest that the cytogenetic investigations should be performed
      in all subjects with abnormal reproductive fitness, for a more accurate
      diagnostic iter.

PMID- 1981384
TI  - Evidence for involvement of N-methyl-D-aspartate receptor in tonic inhibitory
      control of dopaminergic transmission in rat medial frontal cortex.
AB  - Bilateral infusion of DL-2-amino-5-phosphonovalerate (DL-APV) (which is a
      competitive antagonist for N-methyl-D-aspartate (NMDA) receptor) into the medial
      frontal cortex of conscious rats increased the amount of 3,4
      dihydroxyphenylacetic acid (DOPAC) and the DOPAC/dopamine (DA) ratio in the
      cortical area. Moreover, intra-prefrontal injection of DL-APV, D-APV, DL-2-amino
      7-phosphonoheptanoate and 3-[(+/-])-2-carboxypiperazin-4-yl]-propyl-1-phosphonate
      (which are selective NMDA receptor antagonists), but not the L-isomer of APV and
      gamma-glutamyl-aminomethyl sulphonate (a relative antagonist for non-NMDA
      receptors), facilitated prefrontal DA utilization in a NMDA-reversible manner.
      These findings suggest that NMDA-type excitatory amino acid receptors may be
      involved in a tonic inhibitory regulation of dopaminergic transmission in the
      medial frontal cortex in vivo.

PMID- 1981385
TI  - Autoradiographic localization of alpha 2-adrenoceptors in chick brain.
AB  - alpha 2-Adrenoceptors were localized in the chick brain by 'in vitro' receptor
      autoradiography using [3H]UK 14304 as a ligand. High or very high densities of
      binding sites were found in the hyperstriatum, tuberculum olfactorium,
      hypothalamic nuclei, tectum opticum and some medullary nuclei. Comparatively,
      intermediate densities were observed over the thalamic nuclei and locus ceruleus,
      among others. Low densities of alpha 2-adrenoceptors were detected in the
      paleostriatum, hippocampus and cerebellum. Our data indicate that alpha 2
      adrenoceptors in the chick brain present similar properties and homologous
      anatomical distribution to those reported in mammalian brain.

PMID- 1981386
TI  - GABAA and GABAB antagonists prevent the opioid inhibition of endogenous
      acetylcholine release evoked by glutamate from rat neostriatal slices.
AB  - We have examined the role of the GABAergic system in the opioid inhibition of
      endogenous acetylcholine (ACh) release from rat neostriatal slices by blocking
      either gamma-aminobutyric acid-A (GABAA) or GABAB receptors. GABAergic
      antagonists (bicuculline or phaclofen) completely blocked mu- (morphine or DAGO)
      and delta-opioid (DPDPE) inhibition of glutamate-evoked endogenous ACh release in
      a concentration-dependent manner. However, GABA antagonists were ineffective in
      blocking the opioid inhibition of potassium-evoked endogenous ACh release. These
      findings point to the important role of the GABAergic system in the regulation of
      mu- and delta-opioid inhibition of cholinergic neurons stimulated by glutamate.

PMID- 1981387
TI  - Excitatory amino acid neurotoxicity at the N-methyl-D-aspartate receptor in
      cultured neurons: protection by SKF 10,047.
AB  - SKF 10,047 (N-allylnormetazocine) was found to be neuroprotective against
      glutamate-induced excitotoxicity in our model system of energy-stressed neurons
      which rapidly succumb to glutamate via N-methyl-D-aspartate (NMDA) receptor
      mediated events. The 50% protective concentration (PC50) of the (+) and (-)
      enantiomers was 3.3 microM and 9 microM, respectively, against the toxic action
      of 100 microM glutamate. Protection by SKF 10,047 seemed to be mediated by the
      lower-affinity phencyclidine (PCP) binding site rather than the higher-affinity
      sigma-site since the potent sigma-ligand (+)-3-(3-hydroxyphenyl-N-1
      propyl)piperidine [+)-3-PPP) did not protect at concentrations up to 2 mM. A
      reversed stereoselectivity was apparent for neuroprotection since (-)-3-PPP was
      weakly protective with a PC50 of 1.5 mM. These data suggest that energy-stressed
      rat cerebellar granule cells are a useful model for identifying neuroprotective
      agents, as shown by SKF 10,047.

PMID- 1981388
TI  - The pathology of experimental Lasiospermum bipinnatum (Thunb.) Druce (Asteraceae)
      poisoning in sheep. I. Hepatic lesions.
AB  - Poisoning with the plant Lasiospermum bipinnatum was studied in 9 lambs.
      Intraruminal doses, varying from 1-12 g/kg/day of dried plant, were administered
      to 8 animals and 1 was fed 2.5 g/kg/day of the material mixed with maize meal for
      13 days. Periodic serum analyses were done to monitor liver function. Lambs given
      6-12 g/kg/day died or were killed in extremis. Clinical signs included
      progressive anorexia and depression in all these lambs and icterus in 2 animals.
      Lambs given 1-4 g/kg/day were sacrificed after about 2 weeks. Clinical signs in
      these animals were minimal or absent. Hepatosis was found in all the lambs, the
      severity of which correlated with levels of plant administered. Centrilobular
      necrosis and haemorrhage occurred in 2 of the 4 lambs given high doses; single
      cell necrosis of hepatocytes was observed with intermediate doses, and diffuse
      degeneration, which was more severe peripherally, was seen at various doses. In 1
      lamb, degeneration was most severe midzonally. Bile ductule epithelial
      proliferation was observed in 7 of the 9 poisoned animals. Marked hypertrophy of
      hepatocellular smooth endoplasmic reticulum was seen in 3 lambs given low doses.
      The hepatic lesions were compared with those reported for poisoning by other
      hepatotoxic plants belonging to the family Asteraceae and found to be
      indistinguishable.

PMID- 1981389
TI  - Intrathecal and epidural somatostatin in rats: can antinociception, motor effects
      and neurotoxicity be separated?
AB  - In the present investigation, the antinociceptive, motor blocking and neurotoxic
      effects of intrathecal and epidural somatostatin (SST) were assessed in rats
      implanted with lumbar intrathecal and epidural catheters. The doses studied were
      5, 7.5, 10, 12.5 and 15 micrograms intrathecally and 100, 250, 400 and 500
      micrograms epidurally. It appears that if the intrathecal doses of SST are kept
      below 15 micrograms and the epidural doses below 250 micrograms, the prolonged
      tail-flick latency can be separated from the transient motor blockade. The
      antinociception appears not to be attributable to neurotoxicity by the
      histological evidence available.

PMID- 1981390
TI  - [Effect of H1- and H2-histamine receptor blockaders on lesions of the gastric
      mucosa evoked by exogenous histamine in guinea pigs].
AB  - It was demonstrated in experiments on guinea pigs with the use of a histamine
      model of ulcerogenesis that blocking agents of H1-histamine receptors produced a
      more marked gastro-protective effect than H2-antagonists. The results of the
      study confirm the hypothesis that histamine-induced ulceration of the gastric
      mucosa occurs through the mediation of H1-receptors. H2-histamine receptors play
      a secondary role in this process.

PMID- 1981391
TI  - Propranolol treatment of paruresis (psychogenic urinary retention): a brief case
      report.
AB  - Propranolol, a nonselective beta-blocker, was administered to a client with
      paruresis (psychogenic urinary retention) following a novel in vivo exposure
      treatment. The client did not report a significant increase in his ability to
      urinate in public facilities during subsequent exposures. Rationale for including
      propranolol as an adjunct to exposure therapy of paruresis is discussed.

PMID- 1981392
TI  - Resetting of renal autoregulation in conscious dogs: angiotensin II and alpha1
      adrenoceptors.
AB  - It has recently been shown, that common carotid occlusion (CCO) impairs
      autoregulation of renal blood flow (RBF) and glomerular filtration rate (GFR).
      This study was designed to investigate the mechanisms by which a moderate
      sympathetic stimulus influences RBF and GFR autoregulation. CCO provided a
      moderate sympathetic stimulus, and impaired autoregulation by increasing the
      lower autoregulatory limit of RBF and GFR by 21-30 mmHg. Basal RBF and GFR were
      not affected. A low-dose intrarenal infusion of the alpha 1-adrenoceptor agonist
      methoxamine (which did not change total RBF or GFR) induced a similar shift as
      CCO (n = 5, RBF: +31 +/- 11 mmHg, P less than 0.05; GFR: +24 +/- 4 mmHg, P less
      than 0.01). In another group it was shown, that a combination of CCO with an
      intrarenal angiotensin II (A II) blockade (saralasin) did not significantly alter
      the response to CCO (n = 7). These data suggest an alpha 1-adrenergic pathway for
      the sympathetic resetting of autoregulation. An augmented A II formation does not
      play a major role in mediating this effect.

PMID- 1981393
TI  - GABAergic and dopaminergic transmission in the rat cerebral cortex: effect of
      stress, anxiolytic and anxiogenic drugs.
AB  - Benzodiazepines produce their pharmacological effects by regulating the
      interaction of GABA with its recognition site on the GABAA receptor complex. In
      fact, the anxiolytic effect of benzodiazepines may be considered the consequence
      of the activation of the GABAA receptors induced by these drugs. On the contrary,
      beta-carboline derivatives which bind with high affinity to benzodiazepine
      recognition sites modulate the GABAergic transmission in a manner opposite to
      that of benzodiazepines. Thus, these compounds reduce the function of the GABA
      coupled chloride channel and produce pharmacological effects (anxiogenic,
      proconvulsant and convulsant) opposite to those of benzodiazepines. Taken
      together, these data strongly indicate that the GABAA receptor complex plays a
      major role in the pharmacology, neurochemistry and physiopathology of stress and
      anxiety. This conclusion is further supported by the finding that the function of
      the GABAA/benzodiazepine receptor complex may be modified by the emotional state
      of the animals before sacrifice. Accordingly, using an unstressed animal model,
      the 'handling-habituated' rats, it has been demonstrated that stress, like
      anxiogenic drugs, decreases the function of GABAA receptor complex, an effect
      mimicked by the in vivo administration of different inhibitors of GABAergic
      transmission and antagonized by anxiolytic benzodiazepines. Moreover, a long
      lasting down regulation of GABAergic synapses can be obtained after repeated
      administration of anxiogenic, proconvulsant and convulsant negative modulators of
      GABAergic transmission. The latter finding further suggests that GABAergic
      synapses undergo rapid and persistent plastic changes when the GABAergic
      transmission is persistently inhibited. Finally, the evidence that the activity
      of mesocortical dopaminergic pathways is altered in opposite manner by drugs that
      either inhibit or enhance the GABAergic transmission indicates that GABA has a
      functional role in regulation of dopaminergic neurons in the rat cerebral cortex.
      Altogether these results suggest that cortical GABAergic and dopaminergic
      transmission play a major role in the pharmacology, neurochemistry and pathology
      of the emotional states and fear.

PMID- 1981394
TI  - Central serotonergic function in parasuicide.
AB  - 1. Central 5-HT is thought to be involved in neuronal inhibition and as such as a
      modulating influence in restraining the organism from responding to (e.g.,
      especially adverse) stimuli. 2. Evidence for a role of central 5-HT in suicide
      arises from reduced concentrations of brain 5-HT or 5-HIAA in brain stem, reduced
      binding of [3-H]-IMI in brain tissue of frontal cortex/hypothalamus, and
      increased binding of radioligands to 5-HT-2 receptors in the frontal cortex. 3.
      Evidence for a role of central 5-HT in parasuicide arises from reduced
      concentrations of lumbar CSF 5-HIAA, reduced PRL responses to d,l-fenfluramine
      challenge, and increased CORT responses to 5-HTP challenge. 4. Since reduced
      central 5-HT activity appears to be consistently associated with impulsive
      aggression, it is possible that suicidal and parasuicidal acts in individuals
      with evidence of reduced central 5-HT activity are a manifestation of reduced
      impulse control. 5. Agents which enhance central 5-HT function and/or diminish
      the activity of neuronal systems involved in arousal (e.g. norepinephrine or
      dopamine) should be efficacious in reducing parasuicidal behavior.

PMID- 1981395
TI  - Central D1- and D2-receptor occupancy during antipsychotic drug treatment.
AB  - 1. It has been unequivocally shown that antipsychotic compounds reduce
      dopaminergic transmission. A relationship in vitro between the potency for the
      antipsychotic effect and the blockade of D2-dopamine receptors has been shown. No
      such relationships have been demonstrated for any other central receptor
      population. 2. Positron emission tomography (PET) has made it possible to
      investigate interactions of psychotropic drugs with central receptors in the
      living human brain. Using the selective D2 receptor antagonist raclopride
      labelled with positron emitting isotope 11C, it has been shown that chemically
      distinct classical neuroleptics in conventional doses occupy a high degree (65
      89%) of the D2-receptors in the human brain. The results substantiate the opinion
      that the antipsychotic effects is mediated by a blockade of D2-dopamine
      receptors. 3. The degree of binding to D1-receptors using the 11C-labelled D1
      antagonist from Schering (SCH 23390) as the ligand was also determined. The D1
      receptor occupancy seemed to be dependent on the type of the antipsychotic
      compound studied. 4. The atypical neuroleptic compound clozapine demonstrated a
      different binding profile than the classical neuroleptics. Thus, clozapine in
      conventional doses occupied D2-receptors to a smaller extent (40%, 40%, 65%) than
      classical neuroleptics. The occupation of D1-receptors was higher (40%, 42%) than
      that of classical compounds (0-36%). 5. The unique clinical profile of clozapine
      may be related to its potency on both D1- and D2-receptors. The distribution of
      D1-receptors varies from that of D2-receptors in the human brain which may be one
      reason for the importance of blocking both D1- and D2-receptors for a full
      antipsychotic response.

PMID- 1981396
TI  - Modulation of high-affinity CNS dopamine D2 receptor by L-pro-L-leu-glycinamide
      (PLG) analogue 3(R)-(N-L-prolylamino)-2-oxo-1-pyrrolidineacetamide.
AB  - 1. In our previous studies, we reported that one of the conformationally
      constrained analogues of PLG, 3(R)-(N-L-prolylamino)-2-oxo-1-pyrrolidineacetamide
      (PAOPA), was found to be extremely potent in enhancing the [3H]ADTN binding when
      membranes were preincubated with this compound. The PAOPA was without effect when
      directly added to assay tubes. In this study, the compound PAOPA was examined on
      agonist binding to high affinity state of the dopamine D2 receptor. 2. The potent
      analogue PAOPA was able to prevent the GTP-induced conversion of high affinity
      state of dopamine D2 receptor to low affinity state. 3. PLG analogue PAOPA
      modulates the affinity states of the dopamine D2 receptor possibly by affecting
      its interaction with the G-protein(s).

PMID- 1981399
TI  - [Anaerobic non-clostridial microflora in necrotic phlegmons of the face and
      neck].

PMID- 1981398
TI  - The effect of Xylometazoline on the mucosa of human maxillary sinus.
AB  - A stuffy and running nose are two of the most expressed symptoms of acute
      rhinosinusitis and have made the use of decongestants very common. The
      medication, oral or nasal, gives relief from symptoms but its effect on the
      healing of the infection, positive or negative, is not clear. The effect of
      Xylometazoline on the blood flow, the pulse amplitude and the gas exchange in the
      antral mucosa of the maxillary sinus was studied in five healthy subjects. Our
      experiments show that the mucosal pulse amplitude and the blood flow are strongly
      reduced by insufflation of Xylometazoline but the gas exchange in the mucosa is
      only lowered to a minor extent. The reduction in gas exchange is not great enough
      to allow the gas mixture to be altered. The defence mechanisms in the antral
      mucosal lining, i.e. the mucociliary-, the immuno- and the phagocytotic
      mechanisms are all dependent on the blood flow and the gas exchange through
      narrow maxillary ostia of the pumping effect generated by the mucosal pulse wave.
      The reduction in blood flow and pulse amplitude in the maxillary mucosa caused by
      Xylometazoline leads us to consider that, although not harmful then it is at
      least not helpful, in healing rhinosinusitis. Since oral decongestants have
      almost the same effect on the mucosa as nasal decongestants, we do not think that
      any of the medicines faciliate the healing of infections in the upper airways
      even if they make the patient feel better during the infection.

PMID- 1981397
TI  - [Drug combinations in the treatment of arterial hypertension].
AB  - The discovery of new classes of antihypertensive drugs has changed the therapy of
      essential arterial hypertension. New combinations of antihypertensive drugs are
      also possible. The aim of the present work is to give practical guidelines for
      the prescription of an association of antihypertensive drugs and to present a
      review of the current literature on the efficacy and safety of these therapeutic
      combinations.

PMID- 1981400
TI  - Hepatocellular carcinoma in South African Indians resident in Natal.
AB  - Hepatoma is a rare disease in Natal Indians. It occurs in male patients in the
      fifth decade. They have no history of alcohol intake. The main presenting feature
      is abdominal pain, weight loss and hepatomegaly. Blood tests reveal a raised
      alkaline phosphatase, hypoalbuminaemia, hypergammaglobulinaemia and markedly
      raised gamma glutamyl transferase. The tumour is a single large expanding mass in
      the right lobe. The patient usually presents in a late stage of the illness and
      shows a progressive downhill course. Hepatitis B virus infection is emerging as
      the likeliest carcinogen.

PMID- 1981401
TI  - The influence of hypoxic cell-free perfusion and ischemia on cell morphology in
      the proximal tubular S2-segment of the rat kidney.
AB  - In the present study, in-situ perfused rat kidneys were used as a model to
      demonstrate the different morphological changes induced by various periods of
      warm ischemia or of warm hypoxic cell-free perfusion. Light and electron
      microscopic evaluation revealed no changes in the S2 proximal tubular cells after
      short exposure times of up to 4 min, whereas longer periods resulted in changes
      ranging from slight alterations (at 10 min) to severe damage (at 60 min). Warm
      hypoxic cell-free perfusion induced obvious alterations in the proximal tubular
      cells somewhat sooner than warm ischemia. The microscopical findings were
      consistent with the statistics of a detailed morphometrical analysis performed on
      the mitochondrial diameter. The results were further substantiated by counting
      intramitochondrial electron-dense condensations ('flocculent densities') as
      indicators of irreversible cell alteration.

PMID- 1981403
TI  - Atypical differentiation of bronchiolar epithelial cells following experimental
      pneumonia.
AB  - In the bronchiolar and alveolar epithelial responses to experimentally induced
      organizing pneumonia in the rat evoked by Streptococcus pneumoniae type 25, the
      appearance of lamellar body-containing bronchiolar cells is reported. Such cells,
      which are interspersed among proliferating type 2 pneumocytes in the form of
      intraalveolar and bronchiolar buds, also stain immunohistochemically with
      antisera to alveolyn, a surfactant-associated protein. We believe this phenomenon
      supports an hypothesis that in response to specific stimuli, proliferation of a
      common precursor cell of both the bronchiolar Clara cell and the type 2
      pneumocyte occurs, with varying expression of a latent or precursor capacity for
      surfactant secretion.

PMID- 1981402
TI  - Differentiation-promoting effects of mammary-derived growth inhibitor (MDGI) on
      pluripotent mouse embryonic stem cells.
AB  - Pluripotent embryonic stem cells (line BLC6), when cultivated in vitro as
      embryoid bodies and injected subcutaneously into syngeneic mice, form
      teratocarcinomas consisting of embryonal carcinoma cells and differentiated
      tissues of all three primary germ layers. In order to study the possible effects
      of the mammary-derived growth inhibitor (MDGI) on the differentiation pattern of
      the tumors developing in the mice, BLC6 cell-derived embryoid bodies were treated
      in vitro for 4 days with either MDGI or a synthetic peptide composed of the C
      terminal 11 amino acids of MDGI. In those tumors, significantly more
      differentiated neural tissue and lesser proportions of undifferentiated embryonic
      carcinoma cells (ECC) were found in the MDGI- and peptide-treated groups,
      compared with controls. The results are discussed with respect to a possible
      differentiation-promoting capacity of MDGI.

PMID- 1981404
TI  - Absence of the Epstein-Barr virus genome in the normal thymus, thymic epithelial
      tumors, thymic lymphoid hyperplasia in a European population.
AB  - It has previously been shown that the Epstein-Barr virus (EBV) genome may be
      detected in some thymic tumors. We have investigated specimens of normal thymus,
      thymitis with lymphoid hyperplasia and a large spectrum of thymic epithelial
      tumors obtained from european patients for the presence of EBV genome by in situ
      hybridization and DNA-blotting methods. Cell lines established from seven of the
      thymic tumors were also tested for EBV. No EBV genome was demonstrated in any of
      the tumors examined, which included various types of thymoma and thymic
      carcinomas, nor in the non-neoplastic thymic specimens. However, unlike previous
      reports, no examples of lymphoepithelial-like thymic carcinoma, nor specimen from
      Asian patients were included in this study. We suggest that EBV is linked to a
      specific epithelial tumor type, namely the lymphoepithelial-like carcinoma,
      regardless of its site, and not to thymic tumors in general.

PMID- 1981405
TI  - Eosinophilic globule cells in mouse MFH-like sarcomas. Light and electron
      microscopic studies.
AB  - Light and electron microscopic observations were made on eosinophilic globule
      (EG) cells found in 27 subcutaneous malignant fibrous histiocytoma (MFH)-like
      sarcomas in aged ICR mice. These tumors, which were composed of fibroblast-like
      cells as the major component, with small numbers of histiocyte-like cells and
      undifferentiated cells, showed one or more of five growth patterns: storiform,
      pleomorphic, fascicular, myxoid, and hemangiopericytoma-like. EG cells were
      interspersed among the tumor cells and were also present in metastatic lesions.
      They were pleomorphic in shape and contained various numbers of cytoplasmic
      globules, which were positive with the periodic acid-Schiff reaction and
      resistant to diastase digestion. Electron microscopic observation revealed that
      these cells had small finger-like and pseudopodia-like projections, and contained
      varied numbers of characteristic osmiophilic globules and glycogen particles in
      the cytoplasm which seemed to become more abundant as the cells differentiated.
      The osmiophilic globules consisted of a dense homogeneous core and a marginal
      area rich in small vesicular membranous structures. A small population of EG
      cells exhibited features suggesting differentiation to fibroblasts; these were
      characterized by an increased amount of rough endoplasmic reticulum. It is
      suggested that the EG cell is a neoplastic cell, perhaps derived from a primitive
      mesenchymal cell, although an inflammatory cell origin is also possible.

PMID- 1981406
TI  - A quantitative study of epithelial alterations during the early stages of
      experimental colonic tumorigenesis in mice.
AB  - The weekly administration of 1,2-dimethyl-hydrazine (DMH) by subcutaneous
      injection for a period of 16-20 weeks is a well known procedure for producing
      colonic tumors in mice and rats. Quantitative histomorphological, histochemical
      and kinetic studies, as well as investigation of the significance of epithelial
      cell density were carried out in mice between the 7th and the 91st day after the
      first DMH injection. These studies showed that between the 28th and the 35th day,
      several simultaneous alterations in the colonic epithelium involving modification
      of glandular form, decreased mucus secretion, an increase in epithelial cell
      density and an increase in the number of S phase cells (BrdU labeling index: LI).
      Around the 35th day, the glands tended to expand and from the 35th to the 63rd
      day, they were stretched and displayed compartments of dedifferentiated and non
      mucinous crypts (DNMC). In these crypts the cell density became very high,
      reaching twice the control value on the 91st day. This feature was accompanied by
      alteration in cell morphology and by an increase in the available basement
      membrane area. A decrease in mucus secretion was apparent from the 14th day and
      by the 63rd day, mucus secretion was only about 60% of the control value in all
      crypts. The LI was increased until the 35th day following which a paradoxical and
      progressive decrease occurred in all glandular compartments.

PMID- 1981407
TI  - Analysis of Epstein-Barr viral genomes in lymphoid malignancy using Southern
      blotting, polymerase chain reaction and in situ hybridization.
AB  - 109 malignant lymphomas were surveyed by Southern blot analysis and polymerase
      chain reaction (PCR) for Epstein-Barr virus (EBV) DNA and compared with 16
      examples of non-neoplastic lymphadenopathy and 4 normal thymuses. In specimens
      positive by the method of Southern and PCR, in situ hybridization studies were
      performed on formalin-fixed, paraffin-embedded sections. By Southern blot
      analysis, two of seven Hodgkin's disease samples (29%) (one of mixed cellularity
      and the other of lymphocyte predominance type), three of 56 B-cell lymphomas
      (5.6%) and five of 46 T-cell lymphomas (11%) demonstrated EBV DNA. However, the
      16 examples of lymphadenitis and the 4 normal thymuses showed no EBV DNA. With
      PCR, EBV DNA was identified in one B-cell lymphoma, nine T-cell lymphomas, ten
      lymphadenitis specimens and two of the normal thymus, in addition to the positive
      specimens determined by the Southern blotting method. These results indicate that
      the presence of EBV DNA is not related to lymphoid malignancy, but enhancement of
      the DNA is demonstrated in some neoplastic conditions. By in situ hybridization,
      EBV genomes were not detected in all PCR-positive cases, but only in those
      positive by Southern blot analysis.

PMID- 1981408
TI  - Results of the First International Granulocyte Serology Workshop.
AB  - Eleven laboratories participated in the First International Workshop of
      Granulocyte Serology. Participants were asked to identify any granulocyte
      reactive antibodies present in 12 human sera distributed as unknown samples.
      Granulocyte immunofluorescence and granulocyte micro-agglutination were the most
      commonly used techniques. The incidence of false-positive and false-negative
      reactions was 15 and 4%, respectively. Most laboratories were able to distinguish
      between granulocyte-specific and anti-HLA antibodies using platelet absorption.
      The identification of the specificity of granulocyte-specific antibodies caused
      the most problems; these were correctly identified on only 57% of occasions.

PMID- 1981409
TI  - Retroviral infections transmitted by blood transfusion.
AB  - Modifications in donor screening and the introduction of laboratory testing of
      donated blood for anti-HIV-1 and anti-HTLV-I have resulted in a significant
      reduction in the risks of retroviral infections from blood transfusion.
      Presently, the American Red Cross detects an average of eight carriers of human
      immunodeficiency virus, type 1 (HIV-1) per 100,000 otherwise acceptable blood
      donors (0.008 percent), compared with an average of 35 per 100,000 (0.035
      percent) when testing for HIV-1 antibodies began in 1985. Surveillance studies in
      the United States indicate a small likelihood that HIV-2 carriers will pass
      current screening procedures and be accepted as blood donors. Even if an HIV-2
      infected person were to be accepted as a blood donor, there is a 42-92 percent
      likelihood that this person's blood would be detected as infective for HIV-2 and
      excluded because of serological cross-reactions that occur in the EIA for HIV-1
      antibodies. During 1989, which was the first year that donated blood was
      routinely tested for antibodies to human T-lymphotropic virus, type I (HTLV-I) in
      the United States, approximately nine in 100,000 donors (0.009 percent) were
      confirmed positive for antibodies to HTLV-I, and their donated blood was
      excluded. Subsequent testing has revealed that a significant number of these
      persons whose sera was reactive by the HTLV-I EIA were, in fact, infected by HTLV
      II. Epidemiological studies of human retroviral infections (HIV-1, HIV-2, HTLV-I,
      and HTLV-II) continue to provide important data and direction for improving
      criteria for qualifying blood donors.

PMID- 1981410
TI  - [Drug therapy under physical conditioning and during phase III rehabilitation in
      patients following acute myocardial infarct].
AB  - In the framework of the secondary prevention after acute myocardial infarction
      the interaction between physical conditioning (pK) and medicamentous therapy was
      analysed and a retrospective evaluation of the therapy was performed during the
      rehabilitation phase III. During the physical conditioning (n = 110) in 31% of
      the patients changes of the medicamentous therapy rendered themselves necessary
      (15% increase of the dose, 16% reduction of the dose and withdrawal of a
      medicament, respectively). In the rehabilitation phase III (n = 277) 72% of the
      patients were given nitrates, 68% calcium antagonists and 55% beta-receptor
      blocking agents (43% double, 29% triple combinations) and 15% digitoxin. The aim
      of the medicamentous therapy is the treatment of the myocardial ischaemia and its
      sequels, taking into consideration the positive effects of the physical
      conditioning and the influence on the quality of life.

PMID- 1981411
TI  - [Scanning electron microscopic study of the fractured surfaces of Sipal 306
      dental alloy after soldering and laser welding].

PMID- 1981413
TI  - [Morphology and development of dopaminergic neurons in the cat retina].
AB  - Morphology and development of dopaminergic neurons has been studied in the kitten
      retina, using tyrosine hydroxylase (TH) immunocytochemistry. TH immunoreactive
      (TH+) cells are already presented in whole amount and sectioned retina at first
      postnatal day (P1). According to soma size, shape, dendritic process pattern and
      immunoreactivity, two classes, type I or large dark staining TH+ cells and type
      II or small light staining TH+ cells are recognized. The TH I cells which
      consisting of normal placed DA amacrine cells, displaced DA amacrine cells and DA
      interplex-form-like cells, gradually mature during postnatal development, while
      TH II cells decrease quickly and through disappear at P30. After eye opening TH I
      amacrine cells, especially their dendrites develop quickly. The soma diameters
      increase from 11.8 microns (P1) to 14.2 microns (P30). The dendritic fields
      increase in size and complexity. At P1 the thick radiating dendrites emerge from
      the cell body with small or large "spines" and many growth cones. At P13 the
      dendritic field is markedly enlarged and only a few growth cones can be seen on
      some stained dendrites. In addition, the dendritic spines are no longer apparent
      and they are a part of rudimentary rings. By P30 the dendritic plexus of TH+
      dendrites and rings in the out most part of IPL, typical of the adult cells, are
      complete. The influence of light on the development of DA cells after eye opening
      and the possibility of neurotransmitter changing are discussed.

PMID- 1981412
TI  - [The effect of depolymerization of cytoplasmic microtubules on initiation of DNA
      synthesis by growth factors in cells].
AB  - PPP (platelet-poor plasma) alone can not stimulate DNA synthesis in Go C3H/10T1/2
      cells.50 ng/ml of EGF promoted partial Go cells to enter S phase. However, there
      was an apparent synergic effect of simultaneous treatment with 50 ng/ml EGF and
      5%PPP, their synergic effect to stimulate DNA synthesis in Go cells was the same
      as 10% calf serum. Taxol can resist the depolymerization of microtubules. After
      treatment with taxol (10 mumol/L), the progression from Go to S phase in C 3 H 10
      T 1/2 cells was inhibited. This inhibition was especially exhibited at early
      stage of transition from Go to S phase. The result indicated that Go cells can
      not enter S phase without the depolymerization of microtubules. It showed that
      DNA synthesis was stimulated by the simultaneous treatment with colcemid (0.1
      microgram/ml) and growth factors (50 ng/ml EGF + 5% PPP or 10% Calf serum). But
      without the stimulation of growth factors, the unique effect of depolymerization
      of microtubules can not stimulate DNA synthesis. The results present evidence
      indicating that the depolymerization of microtubules has the potency to elevate
      DNA synthesis in Go cells stimulated by growth factors. This potency was also
      appeared at early stage of progression from Go to S phase. We suggest that the
      depolymerization of cytoplasmic microtubules and synergic effect of growth
      factors are involved in account for the transition from Go to S phase in C 3 H 10
      T 1/2 cells.

PMID- 1981414
TI  - Therapeutic interventions which may improve survival in patients with coronary
      artery disease.

PMID- 1981415
TI  - Comparison of Candida albicans adherence to human corneocytes from various
      populations.
AB  - Epidemiological data indicate that patients suffering from diabetes,
      hypothyroidism, obesity, or following prolonged treatment with antibiotics,
      corticosteroids or oral contraceptives, have an increased tendency to develop
      cutaneous candidiasis. Since it is generally believed that attachment of
      microorganisms to host cells is an initial step in the evolution of infection,
      the aim of the present study was to investigate whether cells from susceptible
      individuals have increased capacity to bind the fungus. Corneocytes collected
      from the forearms of individuals of these susceptible groups were exposed in
      vitro to Candida albicans and adhesion to the cells was evaluated in comparison
      with adherence to cells from a non-susceptible population. Adherence in vitro was
      assayed microscopically and evaluated quantitatively by two parameters: 1)
      percentage of adherence - number of corneocytes with adhering yeasts on their
      surface, and 2) the total number of adhered yeasts. Results of the study revealed
      that the mean percentage of adherence and the mean total number of yeasts
      adhering to cells from individuals of the susceptible populations was twice as
      high as values in a healthy population. Statistical analysis of the data by
      Student's t-test indicated that the difference was significant (p less than
      0.001).

PMID- 1981416
TI  - Sodium hydroxide-induced subclinical irritation. A test for evaluating stratum
      corneum barrier function.
AB  - This report concerns the development of a short, simple, non-invasive test for
      assessing sensitivity to irritant dermatitis. Application of NaOH (0.005-2.0
      mol/l) to human skin resulted in significantly greater skin surface water loss
      directly after exposure (1-15 min) than of control (water). The increase in skin
      surface water loss after NaOH application was dose-dependent (0.005-0.1 mol/l)
      and application time-dependent (1-10 min). Application times exceeding 10 min did
      not further increase skin surface water loss and doses higher than 0.1 mol/l
      reversed the effect on skin surface water loss. 15 min after removal of the
      alkali, skin surface water loss baseline values were almost regained. This
      procedure did not cause visible reactions or discomfort for the volunteers. In a
      subsequent experiment, volunteers were exposed to 0.2 mol/l NaOH for 5 min on one
      forearm and to 1% sodium lauryl sulfate for 24 h contralaterally. Skin surface
      water loss after 5 min of NaOH application was significantly correlated with
      transepidermal water loss measurements after 24 h of sodium lauryl sulfate patch
      application. This is, to our knowledge, the first description of a procedure for
      quantifying interindividual differences in stratum corneum barrier function
      without inducing visible changes or causing volunteers discomfort. Use of this
      model should help to further investigate skin barrier function as well as to test
      protective devices and barrier creams.

PMID- 1981418
TI  - Enhanced response of psoriasis to UVB therapy after pretreatment with a
      lubricating base. A single-blind controlled study.
AB  - Forty-three out-patients with stable plaque-type psoriasis involving 10-30% of
      the skin participated in a single-blind controlled study. The psoriasis lesions
      on one half of the body were treated with a lubricating base of the oil-in-water
      type before UVB exposure, while those on the other side of the body received UVB
      only. The rates of improvement of scaling, infiltration and erythema were
      compared in 127 symmetrical pairs of psoriasis plaques. The scores for the three
      variables were then summed to yield a total score for the effect of treatment.
      After only 2 weeks of treatment and throughout the treatment period the rate of
      improvement in the total score was significantly (p less than 0.001) accelerated
      on the body half treated with the emollient compared with the control side.
      Pretreatment with a suitable lubricating base can thus result in shorter
      treatment periods, which means that the surrounding skin will be exposed to
      smaller doses of UVB, with a diminished risk of actinic damage.

PMID- 1981417
TI  - Reactive changes in the Langerhans' cells of human skin caused by occlusion with
      water and sodium lauryl sulphate.
AB  - Human skin was patch tested with sodium lauryl sulphate or with water only for 48
      h and biopsied immediately and after 24 h, then analyzed by immunocytochemistry
      and electron microscopy. Sodium lauryl sulphate produced a decrease in the number
      of epidermal Langerhans' cells and an increase in dermal Langerhans' cells, with
      individual variations. The 48-h water occlusion controls showed only slight
      reactions. Unexpectedly, quite pronounced reactive changes were seen 24 h after
      termination of water occlusion. Thus, dermal Langerhans' cells were commonly
      increased and epidermal Langerhans' cells tended to decrease in number. The
      results indicate that the 24-h interval is not a period of recovery but a period
      in which more pronounced reactive changes occur. Hydration over 48 h followed by
      dehydration leading to temporary damage to the epidermal barrier may explain the
      present findings. Some of the reactive changes observed after sodium lauryl
      sulphate exposure probably represent the additive effects of occlusion and sodium
      lauryl sulphate treatment.

PMID- 1981419
TI  - Prevalence of primary cutis verticis gyrata in a psychiatric population:
      association with chromosomal fragile sites.
AB  - The prevalence of cutis verticis gyrata was studied in a psychiatric
      institutional population of 494 patients, the majority of whom were mentally
      retarded or had chronic schizophrenia. Twenty-two subjects (21 males and 1
      female) were found to have primary cutis verticis gyrata, yielding a prevalence
      of about 4.5%. The frequency of the scalp disorder was 11.4% among mentally
      retarded patients and 1.7% in schizophrenic subjects. A cytogenetic study was
      performed on patients with primary cutis verticis gyrata. In 9 out of 21 subjects
      there was evidence of chromosomal fragile sites: 5 patients had fragile sites on
      the X-chromosome, in 2 there was fragility of chromosome 12 and in 2, fragility
      of chromosome 9. The fragile X-site is the genetic marker of the 'fragile X
      syndrome', a sex-linked inherited disorder often associated with mental
      retardation and other neuropathological findings.

PMID- 1981420
TI  - Acitretin excretion into human breast milk.
AB  - Retinoid transfer into breast milk was studied in a psoriatric woman receiving
      oral acitretin at a dosage of 40 mg once daily. Concentrations of the parent
      compound and its main metabolite, 13-cis acitretin, were measured in serum and
      mature milk during the initial nine days of therapy, using reverse-phase high
      performance liquid chromatography. At steady-state, trace amounts of the drug and
      metabolite (30-40 ng/ml) appeared in breast milk corresponding to a milk/serum
      concentration ratio of about 0.18. Acitretin was almost exclusively distributed
      in the fatty layers of the milk. Although the estimated amount of the drug
      consumed by a suckling infant would correspond to only 1.5% of the maternal dose,
      the toxic potential of acitretin justifies its avoidance in breast-feeding women.

PMID- 1981421
TI  - Skin lesions in renal transplant patients after 10-23 years of immunosuppressive
      therapy.
AB  - Ninety-eight patients with 10-23 years of uninterrupted immunosuppressive therapy
      due to renal transplants were investigated for signs of skin disease. Thirty
      seven per cent had or had had premalignant or malignant skin lesions. This is
      significantly different from a control population (p less than 0.0001). There was
      also a correlation between the length of the immunosuppressive therapy and the
      risk of acquiring squamous cell skin cancers (p less than 0.05). Fifty-five per
      cent had common viral warts at the time of the present examination. The duration
      of immunosuppressive therapy also correlated with the presence of warts (p less
      than 0.01). Seven patients had mycosis and four patients had seborrheic eczema.
      In one-third of the patients the skin appeared normal.

PMID- 1981422
TI  - Parental education in the treatment of childhood atopic eczema.
AB  - To evaluate the role of health education in the treatment of childhood atopic
      eczema, an eczema school was arranged for the parents. Fifty consecutive patients
      (aged 4 months-6 years 2 months) with atopic eczema of varying severity were
      randomly assigned into two groups; one group receiving routine information given
      by the physician during the medical visit, and the other group also visiting a
      trained nurse to receive further information on eczema treatment and practical
      training in controlling atopic eczema. The therapeutic effect was better in the
      group which had received extra guidance. We suggest that systematic training in
      eczema treatment should be organized as an important part of eczema treatment.

PMID- 1981423
TI  - Expression of protein kinase C isozyme in human Langerhans' cells.
AB  - Protein kinase C is a key molecule controlling signal transduction into the cell.
      We recently reported that protein kinase C II isoenzyme, but neither I nor III
      isozyme, was expressed in epidermal Langerhans' cells of the adult mouse, and
      that none of these isozymes was detected in keratinocytes. In this study, we
      examined the expression of protein kinase C isozymes in human Langerhans' cells
      in vivo to see whether the expression of protein kinase C II isozyme in
      Langerhans' cells is a mouse-specific trait. Immunohistochemical studies revealed
      that protein kinase C II isozyme, but neither I nor III isozyme, was expressed in
      epidermal Langerhans' cells. None of these isozymes was detected in
      keratinocytes. These results suggest that the expression of protein kinase C II
      isozyme in epidermal Langerhans' cells in vivo is not a mouse-specific trait and
      that protein kinase C II isozyme is a novel phenotypic marker for epidermal
      Langerhans' cells in human as well as mouse skin.

PMID- 1981424
TI  - Induction of Langerhans' cell mitosis in vivo after orchiectomy on mice.
AB  - We recently reported that male mice have fewer Langerhans' cells (LCs) than
      females and that orchiectomy resulted in an increased LC density. In this study
      we demonstrate that orchiectomy induces a transient increase in the number of
      paired LCs (PLCs) before the increase in LC density occurs. The results of double
      staining for adenosine triphosphatase (ATPase) and 5-bromo-2'-deoxyuridine (BrdU)
      showed that all examined PLCs had incorporated the intraperitoneally injected
      BrdU, while only 0.7% of the unpaired LCs were BrdU-positive; that supported the
      notion of PLCs as being divided daughter LCs. Orchiectomy appears to induce a
      transient increase in mitotic activity of LCs resulting in the increased LC
      density.

PMID- 1981425
TI  - Comparison of the minimal phototoxic dose in topical 4,5', 8-trimethylpsoralen
      PUVA treatment of caucasian skin and of oral mucous membrane.
AB  - The minimal phototoxic dose values for UVA radiation of psoralen-treated skin and
      of oral mucous membrane were studied in 16 healthy volunteers. A commercial 0.01%
      trioxalen ointment was used as the topical photosensitizer. In all 16 persons the
      radiation dose needed to induce erythema was greater for the buccal mucosa than
      for the skin, and the average buccal minimal phototoxic dose was 2.3-fold that of
      the cutaneous minimal phototoxic dose.

PMID- 1981426
TI  - Twenty-nail dystrophy treated with topical PUVA.
AB  - A case of twenty-nail dystrophy treated with topical PUVA is described. The
      patient, a 19-year-old woman, had a 4-year history of a nail dystrophy involving
      all finger- and toe-nails. The finger-nail changes were treated with topical
      PUVA, dose 0.7-1.4 J/cm2 x 3/week. After 7 months excellent improvement was seen,
      while the untreated toe-nails were unaffected. A maintenance dose of 0.7 J/cm2 x
      3/week was necessary to prevent recurrence. We suggest that topical PUVA is worth
      trying for the treatment of twenty-nail dystrophy.

PMID- 1981427
TI  - Intralesional interferon-alpha 2b treatment of basal cell carcinoma.
AB  - Ten patients with histologically proven basal cell carcinoma were treated with
      sublesional injections of interferon-alpha 2 b (Introna), 1.5 x 10(6) units per
      injection, three times per week for 3 weeks. Six of the treated lesions cleared
      completely without further therapy. These lesions measured less than 19 x 19 mm.
      There was no relapse during an observation period of up to 21 months. Non-healing
      tumours were large (greater than 20 x 20 mm) and two of them were of nodular
      type. Side effects were negligible, if present at all. Introna seems to offer a
      valuable alternative treatment for selected cases of basal cell carcinoma, when
      excision or X-ray therapy cannot be performed.

PMID- 1981428
TI  - Chronopharmacokinetics of 5-methoxypsoralen.
AB  - Diurnal variations in drug pharmacokinetics are a well known phenomenon.
      Chronopharmacology studies now appear to be attracting increasing interest with a
      view to establishing an optimum therapeutic prescription. In order to determine
      possible chronobiological variations of 5-methoxypsoralen (5-MOP)
      pharmacokinetic, 5-MOP blood concentrations were quantified in 8 healthy subjects
      after drug ingestion at different times during the day. Stolk's High Performance
      Liquid Chromatography technique was used to assess the 5-MOP serum
      concentrations. Each subject underwent three pharmacokinetic studies after oral
      ingestion of 5-MOP (1.2 mg/kg), in conjunction with a standardized low-lipid
      meal. The first pharmacokinetic study was started in the morning, the second in
      the afternoon and the third in the evening. Drug intake was at intervals of 2
      days, to avoid drug accumulation. The results showed that the evening intake of
      the drug induced a higher 5-MOP maximum concentration and a higher 'area under
      curve' than morning or afternoon ingestion. This study suggests an optimized PUVA
      therapy, when performed in the evening.

PMID- 1981429
TI  - Pemphigus vulgaris associated with pregnancy. A case report from Japan.
AB  - We present a case of pemphigus vulgaris which developed during pregnancy. The
      newborn infant was normal. Bullous lesions were successfully treated by pulse
      therapy with high-dose corticosteroids. This is, to our knowledge, the first
      report in English from Japan describing pemphigus vulgaris associated with
      pregnancy.

PMID- 1981430
TI  - Beneficial response to megoestrol acetate in AIDS-related cachexia and a possible
      megoestrol withdrawal-associated syndrome?
AB  - A man with AIDS is described in whom a profound weight loss was converted into a
      weight gain by treatment with megoestrol acetate, a synthetic progesterone. His
      appetite improved and was accompanied by a feeling of improved well-being.
      Following abrupt discontinuation of the drug, there was a significant but
      transient depression of mood and appetite associated with loss of energy; it is
      suggested that this complex of symptoms might represent a megoestrol acetate
      withdrawal-associated syndrome.

PMID- 1981431
TI  - Alagille syndrome. A case report.
AB  - A 5-year-old physically and mentally retarded female child born of non
      consanguineous parents, who had had disseminated skin lesions for 4 1/2 years, is
      presented. She had persistent neonatal jaundice associated with clay-coloured
      stools and generalized pruritus which receded by the age of 2 years. Examination
      revealed characteristic facies, moderate hepatosplenomegaly, cardiac murmur and
      widespread smooth yellow papules and nodules on ears, trunk, bony prominences and
      palms. Ophthalmic examination revealed corneal opacities. Liver function tests
      and lipidogram were abnormal. A diagnosis of Watson-Alagille Syndrome was made on
      the basis of characteristic facies, xanthomatosis and cholestatic jaundice.

PMID- 1981432
TI  - Ulceration of the palms and soles. An unusual feature of cutaneous T-cell
      lymphoma.
AB  - Two patients, one with Sezary syndrome and one with mycosis fungoides are
      described, in whom lesions on the palms and soles were associated with extensive
      ulceration and gave rise to diagnostic difficulty. Extensive ulceration of the
      palms and soles is uncommon; its presence should alert clinicians to the
      possibility of cutaneous T-cell lymphoma.

PMID- 1981434
TI  - The effect of grenz ray therapy on pustulosis palmoplantaris. A double-blind
      bilateral trial.
AB  - The effect of grenz ray therapy in the treatment of pustulosis palmoplantaris was
      assessed in 15 patients by randomly allocating active treatment of the lesions of
      one side of the body, while the lesions on the other side, which received
      stimulated therapy, served as a control. Four Gy of grenz rays 10 kV were applied
      on 6 occasions at intervals of 1 week. A significantly better therapeutic result
      was recorded on the lesions which had received active grenz ray therapy. However,
      the therapeutic response was moderate. It is concluded that grenz ray therapy
      could be useful in pustulosis palmoplantaris mainly as an adjunct to other
      therapies.

PMID- 1981433
TI  - Papular eruption in helminth infestation--a hypersensitivity phenomenon? Report
      of four cases.
AB  - This communication reports on generalized papular eruption in Man, coinciding
      with infestation due to dwarf tapeworm (Hymenolepis nana), pinworm (Enterobius
      vermicularis) and whipworm (Trichuris trichiura). The assumed allergic-hyperergic
      reaction was evident from itching, blood and tissue eosinophilia, increased serum
      IgE and clearing up after focus of infestation therapy. Pinworm and whipworm
      therapy was initially accompanied by Jarisch-Herxheimer phenomenon.

PMID- 1981435
TI  - The effects of tetracyclines and erythromycin on complement activation in vitro.
AB  - The effects of tetracycline, minocycline and erythromycin on complement
      activation in vitro were studied. At concentrations of 100 mg/l or less, these
      antibiotics did not inhibit the capacity of Propionibacterium acnes to cleave C3
      in normal human serum or in serum chelated of Ca2+ allowing complement activation
      by the alternative pathway alone. The antibiotics had no effect (at 100 mg/l) on
      total haemolytic activity of complement in normal human serum. This study did not
      provide evidence to support the hypothesis that the efficacy of these antibiotics
      in the therapy of inflammatory acne vulgaris can be explained by inhibition of
      complement activation.

PMID- 1981436
TI  - A double-blind comparison of topical clindamycin and oral minocycline in the
      treatment of acne vulgaris.
AB  - Sixty-six patients with moderate to severe facial acne vulgaris were entered in a
      12-week double-blind study to compare the efficacy of topical clindamycin
      phosphate 1% twice daily and oral minocycline 50 mg twice daily. Both treatments
      gave significant overall improvements from baseline observations in acne grade
      and inflamed lesion counts, but not in noninflamed lesion counts. There were no
      significant differences between the two treatment groups in respect of acne
      grade, inflamed or non-inflamed lesion counts. Both treatment regimes were well
      tolerated. This study has shown that topical clindamycin twice daily is an
      effective alternative to oral minocycline 50 mg twice daily in the treatment of
      moderate to severe facial acne vulgaris.

PMID- 1981437
TI  - Response of atypical bullous pyoderma gangrenosum to oral minocycline
      hydrochloride and topical steroids.
AB  - An 80-year-old Caucasian female with rheumatoid arthritis and recurrent atypical
      bullous pyoderma gangrenosum is described. There was no evidence of any
      underlying myeloproliferative disorder. Rapid healing occurred in response to
      oral minocycline hydrochloride and topical clobetasol propionate.

PMID- 1981438
TI  - Renal transplantation and isotretinoin.

PMID- 1981439
TI  - Pharmacology and mechanism of action of existing and new neuroleptics.

PMID- 1981440
TI  - [The value of laparoscopy in the diagnostic evaluation of cryptorchism with non
      palpable testicles].
AB  - From 1986 to 1989, diagnostic laparoscopy was performed in 12 boys, before
      operation of non-palpable testes. Cryptorchidism was unilateral in all but one
      case. Preoperative physical examination and ultrasonographic studies of the
      inguinal region had been performed in all of them and failed to localize the
      testis. Laparoscopy demonstrated six intra-abdominal testes in five children:
      five testes were brought down into the scrotum and one was removed because
      endoscopic diagnosis of complete epididymo-testicular dissociation. Four of the
      seven other boys were not operated on because of laparoscopic findings. In the
      last three cases, systematic surgical exploration of the inguinal region was
      performed and demonstrated total atrophy of the testis. Performed in good
      condition the procedure is very safe and simple to achieve. It does not increase
      significantly the duration of the operation and gives objective elements for the
      operative procedure.

PMID- 1981441
TI  - Spread of herpes simplex virus (HSV) strains SC16, ANG, ANGpath and its glyC
      minus and GlyE minus mutants in DBA-2 mice.
AB  - Herpes simplex virus type 1 (HSV-1) strains SC16, ANG, its pathogenic variant
      ANGpath and the mutants ANG-pathgC18 glycoprotein C (glyC) negative and ANGpathI2
      4 (glyE negative) were compared for their ability to spread in DBA-2 mice after
      peripheral inoculation. Virus infectivity assay in 9 organs at days 2, 3, 4, 5,
      6, and 10 post-infection (p.i.) and morphologic examinations (immunofluorescence,
      PAP staining) showed the following: SC16, ANG, and ANGpath spread first (days 2-3
      p.i.) by haematogenic route to spleen, liver, and adrenal gland. Since day 4 the
      invasion of the vegetative and peripheral nervous system took place in SC16 and
      ANGpath-infected mice, followed by virus spread to the spinal cord and brain
      stem. In ANG-infected mice the invasion of peripheral nervous system was minimal
      although both ANG as well as ANGpath spread along the axons. In ANG pathC18
      infected mice a relatively prolonged viraemic phase (days 2-4 p.i.) represented
      with foci of virus antigen-containing cells in spleen, liver, and mesenterial
      connective tissue was accompanied with a low grade invasion of the peripheral
      nervous system (days 3-4 p.i.). No spread by any route of ANGpathI2-4 was
      observed after intraperitoneal inoculation. When comparing ANGpath and SC16, the
      latter seemed slightly more lethal, since ANGpath killed 67.2% of DBA-2 mice
      which were given 2 X 10(6) PFU/0.1 ml by i.p. route as compared to the 100%
      lethality of SC16-infected animals.

PMID- 1981442
TI  - Antiviral activities of pyrimidine nucleoside analogues: some structure--activity
      relationships.
AB  - Seventeen nucleoside derivatives (derived from arabinosylcytosine, resp.
      cytidine, 5-fluorouracil and uracil) were tested by agar-diffusion plaque
      inhibition test for their antiviral activity with herpes simplex, vaccinia, fowl
      plague, Newcastle disease and western equine encephalomyelitis viruses. The
      highest antiviral activity against DNA viruses exhibited arabinosylcytosine, N4
      acylarabinosylcytosines, arabinosylthiouracil, cyclocytidine and its 5'
      chloroderivative. RNA viruses were inhibited by 5-fluorouridine only, whereas
      other tested compounds were ineffective or showing marginal activity only. By
      search for relationship between chemical structure and antiviral activity a
      tendency was found of higher antiviral activity at lower lipophilicity. This is
      probably due to better transport of the studied compounds into cell. The chemical
      structure, however, is the main reason of antiviral activity.

PMID- 1981443
TI  - Studies on the antiviral activity of inorganic heteropolyanions against Semliki
      forest virus in vivo and vaccinia virus in vitro.
AB  - Seven new inorganic heteropolyanions were tested for their antiviral activity.
      One of these, sodium 12-tungstoborate, was found to protect mice from Semliki
      forest virus and mouse embryo fibroblast monolayers from vaccinia virus
      infections. In mice these heteropolyanions exhibited no synergistic antiviral
      activity with the interferon inducing mycoviral double-stranded RNA.

PMID- 1981444
TI  - Isolation and characterization of Sedlec virus, a new bunyavirus from birds.
AB  - A pathogenic agent designated AV 172 was isolated from the blood of a Reed
      Warbler (Acrocephalus scirpaceus) out of 767 samples from birds belonging to 35
      species and 14 families. The birds (largely wetland passerines) were captured in
      the reed-belt littoral of Nesyt fishpond in southern Moravia, Czechoslovakia,
      during the years 1984 to 1987. Virus AV 172 has been found to represent probably
      a new species (designated virus "Sedlec") of family Bunyaviridae. Sedlec virus is
      pathogenic to suckling and adult mice when inoculated intracerebrally (i.c.) but
      not intraperitoneally (i.p.) and its ether-sensitive spherical particles measures
      90-100 nm.

PMID- 1981445
TI  - Antibodies to human coronaviruses 229E and OC43 in the population of C.R.
AB  - Of 1200 human sera tested by enzyme-linked immunosorbent assay (ELISA), 53%
      contained antibodies to human coronavirus (HCV) 229E and 88% to HCV OC43. The
      sera were from persons aged 13 months to 80 years, both males and females, and
      were collected in four different regions in 1986. The percentage of positives
      increased with increasing age and tended to vary according to the geographic
      area. Additional paired human sera from 218 patients with acute respiratory
      diseases (ARD) were collected between October 1986 and June 1987 in Prague.
      Significant antibody rises to HCV strain 229E were detected in 7 (3.2%) patients
      9 months to 17 years old, to HCV strain OC43 in 4 (1.8%) patients under 2 years
      of age.

PMID- 1981446
TI  - Dual infection of Ixodes ricinus ticks with two viruses of the tick-borne
      encephalitis complex.
AB  - Ixodes ricinus female ticks were inoculated with Skalica (SK) virus (non
      pathogenic for adult albino mice by subcutaneous route) and 14 days later they
      were challenged with strain 198 of Tick-borne Encephalitis (TBE) virus (highly
      pathogenic for adult albino mice by subcutaneous route). After additional 14 days
      of incubation, 42.9 to 65.0% of the adult (10-12 g) albino mice infested with
      these double infected ticks developed antibodies to TBE without signs of sickness
      (transmission of SK virus), while paralysis or death was registered in 35.0 to
      57.1% of infested mice (transmission of strain 198) depending on the
      concentration of strain 198 used for inoculation of ticks. However, a low degree
      of interference to superinfection with strain 198 was observed, when the
      dissected tick salivary glands were examined by subcutaneous inoculation of adult
      albino mice (more than 90% of examined salivary glands contained strain 198
      virus).

PMID- 1981447
TI  - Indirect haemolysis test in Q-fever.
AB  - Sheep erythrocytes sensibilized with the lipopolysaccharide (LPS) extracted from
      Coxiella burnetii phase 1 cells were used in indirect haemolysis test (IHT). The
      test was highly sensitive and specific. Its use seemed reasonable when following
      the chronic course of Q-fever by serologic methods.

PMID- 1981448
TI  - Electrophoresis of the complementary strands of the double-stranded Kemerovo
      virus RNAs in agarose-urea gel.
AB  - Single-stranded (ss)RNAs derived from 10 double-stranded (ds)RNA segments of
      Kemerovo virus (KV) were separated into 13 RNA bands by agarose-urea gel
      electrophoresis. The complementary strands of the dsRNA segments 1, 9 and 10
      displayed different electrophoretic mobility. An attempt was made to determine
      the origin of the ssRNA bands. The ssRNA bands originating from the dsRNA
      segments 1, 2, 3, 9 and 10 were identified unequivocally, while those originating
      from the dsRNA segments 4, 5, 6, 7 and 8 were characterized partially. The minus
      RNA strands of the dsRNA segments 9 and 10 exhibited higher electrophoretic
      mobilities as their complementary plus RNA strands.

PMID- 1981449
TI  - Growth of Igbo-Ora virus in some tissue cultures.
AB  - VERO, MRC5, MDCK, and MA104 cells were tested for their ability to support the
      growth of Igbo-Ora virus. In VERO and MRC5 cell cultures the virus replicated to
      high titres causing apparent cytopathic effects (CPE) (cell rounding and complete
      lysis) and formation of complement fixing antigens. The virus grew to lower
      infectious titre in MDCK and MA104 cell cultures in which CPE was limited to cell
      rounding only.

PMID- 1981450
TI  - Detection of antibodies to the western and the eastern type of haemorrhagic fever
      with renal syndrome in patient's sera from Slovakia.
AB  - We present serological evidence of infection with western and eastern type of
      haemorrhagic fever with renal syndrome (HFRS) virus in patient's sera from
      Slovakia by indirect immunofluorescence. Treatment of sera with 2-mercaptoethanol
      decreased levels of haemagglutination-inhibition (HI) antibodies to the eastern
      type of HFRS suggesting primary infection of the patients by this virus.

PMID- 1981451
TI  - Relationship between the prostaglandin cascade and virus infection.
AB  - Several prostaglandins are continuously produced in every cell. They activate
      protein kinases by regulating cyclic nucleotide synthesis. Modifications of the
      phosphorylation of virus polypeptides and alterations in the microtubular system
      of host cells can result in the reactivation of latent viruses. Prostaglandins
      have a very important role in directing cell cycle. Abnormal tyrosine kinase
      activities during viral cell transformation are responsible for the malignant
      changes and consequently severe alterations are observed in the endogenous
      prostaglandin production. External modification of this cascade can revert
      malignant signs to normal. Furthermore, virus infection or cell transformation
      could be promoted by the immunosuppressive effects of overproduced
      prostaglandins. They damage interferon release and co-operation between the
      different cell types of the immune system. Enzyme inhibitors of the prostaglandin
      cascade or prostaglandin analogues may exert influence on all of these
      phenomenon, providing future therapeutic agents.

PMID- 1981452
TI  - Comparison of the action of ionizing radiation and UV-light on lambda phage.
      Influence on phage adsorption, DNA injection, replication, and DNA repair.
AB  - The influence of gamma radiation, X-rays, UV-light at 254 nm and 365 nm, the
      latter combined with furocoumarin sensitizers has been studied on plaque forming
      ability, phage adsorption, DNA injection, and replication processes. UV-light
      (365 nm) plus furocoumarin treatment of phage particles gave rise to two types of
      DNA crosslinks. Type I crosslink corresponded to furocoumarin mediated covalent
      linkage between adjacent sites in opposite strands of the double helix. Crosslink
      type II (hairpin crosslink) required a highly condensed DNA and corresponded to
      the covalent linking of adjacent sites in double helical segments of a folded DNA
      molecule. The relationships of the type I crosslinks to inhibition of DNA
      replication and of the type II crosslinks to suppression of the DNA injection
      process are discussed. Pronounced deviations in phage inactivation have been
      obtained by X-ray radiation alone compared with UV-light (254 nm) pretreated and
      subsequently X-ray irradiated probes. The observed protective effect of the
      latter was described in terms of an inducible repair mechanism. The same
      protection has been observed by combination of gamma radiation with a sublethal
      UV-light (254 nm) dose.

PMID- 1981453
TI  - Lymphokine release as measurement of anti-mouse hepatitis virus type 3 (MHV3)
      cellular reactions in various mouse lines exhibiting differential
      susceptibilities to MHV3-induced paralysis.
AB  - We found that susceptibility to Murine Hepatitis Virus, type 3 (MHV3)-induced
      paralysis is controlled by genes of the H-2 complex. In this article, we compared
      MHV3 antigen specific cellular reactions, in congenic mice harbouring different H
      2 genes (or gene). In a first set of experiments, paralysis susceptible (B10.A x
      A/J)F1, partly susceptible (B10.AQR x A/J)F1 and resistant (B10.Q x A/J)F1
      hybrids were infected with live MHV3. Three weeks or more post-infection (p. i.),
      the spleens and peritoneal exudate (PE) cells from the mice were put into
      culture. Killed MHV3 was added to cultures, and antigen specific lymphokine
      production and utilization were measured: IL-1 production by PE cells after 24 hr
      in culture, IL-2 production by splenocytes after 24 hr in culture, IL-2
      utilization (as appraised by splenocyte proliferation) after 96 hr in culture. No
      clearcut difference, resulting from genetic disparity, could be observed in the
      antigen-specific responses. In a second set of experiments, mice were primed with
      ultra-violet radiation killed MHV3. In that case, increases of IL-1 production by
      PE cells, of IL-2 production by splenocytes and splenocyte proliferation were
      always observed, compared to PE cells and splenocytes from non-primed (control)
      donor mice. However, in latter case, addition of MHV3 antigen to cultures did not
      result in augmentation of antigen specific IL-2 production and utilization. Here
      again, no genetic effect was observed. We conclude from these results that MHV3
      infection elicited strong lymphokine responses, but that antigen-specific IL-1
      and IL-2 production did not correlate with the susceptibility to MHV3-induced
      paralysis.

PMID- 1981454
TI  - Identification of an infectious laryngotracheitis virus equivalent to the herpes
      simplex virus type 2 major DNA binding protein (ICP8).
AB  - A region of homology between the genomic DNA of infectious laryngotracheitis
      virus (ILTV), an avian herpesvirus, and the region encoding the herpes simplex
      virus type 2 (HSV-2) major DNA binding protein (ICP8) has been detected by the
      use of nick translation and Southern blot analysis. Further, a monoclonal
      antibody directed against the HSV-2 ICP8 protein detected has antigenic cross
      reaction with ILTV as demonstrated by indirect immunofluorescence.

PMID- 1981455
TI  - Influenza virus detection in clinical specimens.
AB  - The authors compared the results of influenza A (H1N1) and influenza A (H3N2)
      virus detection in nasopharyngeal swabs from flu patients by molecular
      hybridization (MH), ELISA, virus isolation and seroconversion. Using the
      immunofluorescence (IF) technique influenza virus was detected in cell
      suspensions from the first chick embryo passage. Altogether 63 swabs from various
      epidemic seasons were separated into 3 groups according to specimen sampling and
      storage. It was shown that influenza virus RNA could be found in 16 out of 22
      swab specimens (72%) stored at -70 degrees C without thawing and that ELISA
      revealed the influenza virus antigen in 19 cases (86%); in contrast, IF was
      positive in 6 (27%) and virus isolation in 5 (22%) cases only. However, the
      positive rate of MH decreased to 9% in 21 swab specimens repeatedly thawed and
      stored at -20 degrees C and was completely negative after prolonged storage of
      repeatedly thawed samples. Despite these conditions, ELISA was still successful
      in both latter sample groups (71-80%). For specificity control, 29 samples coming
      from patients with influenza B virus and other respiratory virus diseases (adeno-
      and respiratory syncytial virus) were used.

PMID- 1981457
TI  - Immunological markers in patients with different forms of viral hepatitis B
      treated by "conventional" therapy or with HuIFN alpha.
AB  - Selected immunological, biochemical, and other viral hepatitis B (VH-B) markers
      were followed and analysed during "conventional" or human interferon alpha (HuIFN
      alpha) therapy of patients with different forms of VH-B. The immunological data
      obtained from "conventionally"-treated acute hepatitis B (AH-B), prolonged acute
      hepatitis B (AH-BP) or chronic active hepatitis B (CAH-B) patients disclosed
      differences unsatisfactory for comparison of the influence of HuIFN alpha therapy
      on changes of the immunological markers. More valuable data were obtained through
      continuous registration of the dynamics of selected blood markers. Partial
      effects on immunological parameters were seen after HuIFN alpha administration to
      2 patients with developing CAH-B infection. Progression of the disease was
      markedly halted in these both patients after IFN treatment.

PMID- 1981456
TI  - Transient increase of HBsAg levels following human IFN alpha treatment signalises
      the patient's response in chronic active hepatitis B.
AB  - Eleven patients in early stages of chronic active hepatitis B (CAH-B) were
      treated for weeks or months with a natural or recombinant human interferon alpha
      (Hu IFN alpha). Changes of serum levels of selected hepatitis B virus (HBV)
      markers were observed after Hu IFN alpha administration. Increase of HBsAg level
      accompanied by more or less simultaneous HBeAg level depression was the most
      interesting observation. These changes were well expressed in 5 reactive patients
      only; they usually ceased after withdrawal of IFN therapy. Reaction of the
      remaining 6 patients was either poor or not demonstrable. The possible mechanism
      for HBsAg/HBeAg serum level changes during the IFN therapy of CAH-B is discussed.

PMID- 1981458
TI  - Latency competence of herpes simplex virus strains ANG, ANGpath and its gC and gE
      minus mutans.
AB  - The latency competence of herpes simplex virus type 1 (HSV-1) strains SC16, KOS,
      ANG, ANGpath and its mutants ANGpathgC18 (gC minus, spontaneous point mutation),
      KOSgC39 (gC minus deletion), ANGpathI2-4 (gE minus deletion), and ANGpathgCI-8
      (gE and gC minus double mutan) was compared and DBA/2 mice. While the latent SC16
      and KOS reactivated spontaneously in explanted homolateral trigeminal ganglion
      fragments coming from Velaz DBA/2 mice, methylation inhibitor 5-azacytidine (5
      AzaC) was required to achieve reactivation of SC16 in the ganglion explants from
      Hannover DBA/2 mice. Reactivation of ANGpath in the cultured trigeminal ganglia
      from both lines of DBA/2 mice occurred only in the presence of the drug. The
      compound also enhanced the reactivation incidence in the ganglion explants from
      ANG-infected Hannover DBA/2 mice but not from Velaz DBA/2 mice: in the latter it
      remained low even in the presence of the inducer. Both gE- mutants failed to
      establish latency as judged by the failure of reactivation either in the presence
      or the absence of 5-AzaC. This seemed in accordance with the absence of neural
      (quick axonal) spread of these mutans in mice (Rajcani et al., 1990). In
      contrast, both gC- mutans established latency: ANGpathgC18 at an unchanged rate
      and KOSgC39 at a lower frequency than the parent strain.

PMID- 1981459
TI  - Intracellular localization of recombinant vaccinia virus produced HIV antigens
      and their use for confirmation of HIV seropositivity.
AB  - Recombinant vaccinia strains vC5 and vE234L expressing the rp50 and rgp160/rgp120
      recombinant proteins were used in immunoblot and immunofluorescence assays. No
      false reactions were found, although 30 sera giving false reactivity with gag or
      env encoded proteins in a commercial immunoblot assay were included into the test
      panel. We recommend the recombinant protein-based assay for confirmation and
      discrimination of HIV seropositivity.

PMID- 1981460
TI  - Radioimmunoassay and oligonucleotide mapping of A/HswlN1 influenza viruses
      isolated from humans and animals.

PMID- 1981461
TI  - A simple and effective method of preparing rotavirus antigen in preparative
      quantities.

PMID- 1981462
TI  - Are animal retroviruses potential candidates for an AIDS vaccine?

PMID- 1981463
TI  - Occurrence and potential importance of angiotensin-converting enzyme in semen of
      boars.
AB  - The activities of angiotensin-converting enzyme (ACE) and leucinaminopeptidase
      (LAP) are positively correlated with corresponding concentrations of sperm cells
      in semen of boars kept under normal conditions. The spermatozoa bound ACE
      activity, in general, does not reflect differences in the quality of semen (bull
      and boars). On the other hand, the ACE activity directly bound on the sperm cells
      is significantly elevated, if 'exogenic noxes' (by feeding or keeping) influence
      the fertility of boars in a drastic manner. These results are discussed with
      regard to the differential diagnostic importance for estimating the semen quality
      and to the causal relations between increased enzyme binding and injury of sperm
      cells.

PMID- 1981464
TI  - Detection of anticonvulsants and their metabolites in urine within a "general
      unknown" analysis procedure using computerized gas chromatography-mass
      spectrometry.
AB  - Detection of the anticonvulsants carbamazepine, clonazepam, diazepam,
      ethosuximide, mephenytoin, mesuximide, methylphenobarbital, phenobarbital,
      phenytoin, primidone, propylhexedrine, sultiame, trimethadion and their
      metabolites in urine is described. The method presented is integrated in a
      general screening procedure (general unknown analysis) for several groups of
      drugs, detecting several hundred drugs and over 1000 metabolites. It includes
      cleavage of conjugates by acid hydrolysis, isolation by liquid-liquid extraction,
      derivatization by acetylation, separation by capillary gas chromatography and
      identification by computerized mass spectrometry. Using mass chromatography with
      the selective ions m/z 58, 104, 113, 117, 165, 193, 204 and 246, the possible
      presence of anti-convulsants and/or their metabolites was indicated. The identity
      of positive signals in the reconstructed mass chromatograms was confirmed by a
      visual or computerized comparison of the stored full mass spectra with the
      reference spectra. The sample preparation, mass chromatograms, reference mass
      spectra and gas chromatographic retention indices are documented.

PMID- 1981465
TI  - Comprehensibility of patient education literature.

PMID- 1981466
TI  - Results of N-methyl-D-aspartate antagonists in perinatal cerebral asphyxia
      therapy.
AB  - Perinatal cerebral asphyxia, which results in significant neurologic and
      cognitive disabilities in infants and children, remains a major health problem.
      Potential neurologic sequelae include cerebral palsy, mental retardation, and
      epilepsy. Over the next few years, neuroprotective agents that prevent asphyxial
      neuronal injury and death are likely to be developed. These agents may also be
      effective in prophylaxis and treatment of chronic neurologic disorders, including
      epilepsy and neurodegenerative disorders, such as Huntington disease.

PMID- 1981467
TI  - CHARGE and Joubert syndromes: are they a single disorder?
AB  - A patient with the CHARGE association (Coloboma of the eye, Heart defect, Atresia
      of the choana, Retarded growth and development, Genital hypoplasia, and Ear
      anomalies or deafness) had intermittent hyperpnea and cerebellar hypoplasia;
      therefore, he had both the CHARGE association and Joubert syndrome. The 2
      syndromes have not been previously linked. We discuss their similarities and
      review the literature.

PMID- 1981468
TI  - Arylsulfatase A (ASA) defect and psychiatric illness. A review.
AB  - The detection of homozygous (disease state) and heterozygous (carrier) forms of
      metachromatic leukodystrophy (MLD) and their prevalence among psychiatric
      individuals are reviewed. Levels of Arylsulfatase A (ASA) activity in peripheral
      leukocytes, mixed white cell populations, and lymphocytes are compared in normal
      and psychiatric patients. The prevalence of low levels of enzyme activity in
      psychiatric patients, and the implications of such levels with regard to the
      metabolic disease states and associated psychiatric illnesses are discussed. In
      addition, the use and reliability of leukocyte enzyme assay systems as a criteria
      for determining and distinguishing between the homozygous and heterozygous
      conditions are evaluated.

PMID- 1981469
TI  - Is spontaneous orofacial dyskinesia an artefact due to incomplete drug history?
AB  - One percent of elderly people living outside of institutions have spontaneous
      dyskinesia. Patients in institutions have an average prevalence of 5% for this
      disorder, with some rates as high as 37%. It is possible that many institutional
      cases are in fact occult tardive dyskinesia related to past antipsychotic drug
      use. A survey of an institutional sample of elderly patients revealed a much
      higher rate of past exposure to antipsychotics (86%) than of current use (26%) in
      organically impaired patients. Despite a high prevalence of dyskinesia, no cases
      were found without past exposure to antipsychotics.

PMID- 1981470
TI  - The ets-1 gene and ataxia telangiectasia.

PMID- 1981472
TI  - Origin of extra chromosome 21 in 343 families: cytogenetic and molecular
      approaches.
AB  - As the knowledge of parental origin and meiotic stage of nondisjunction is the
      prerequisite to evaluation of the possible etiological factors in trisomy 21, we
      have examined 343 families with at least one Down syndrome child. Of these, 322
      were primary trisomies, including 24 mosaics, and 21 were structural
      rearrangements. This study was carried out by analysing chromosome 21 cytogenetic
      heteromorphisms and molecular RFLPs. In our study first maternal meiotic
      nondisjunction (75.3%) is the most common mechanism leading to primary trisomies.
      In the 24 mosaic cases, the most frequent error occurred at the first meiotic
      division (83%). The origin of structural rearrangements was maternal in 15 of 21
      cases. Trisomy 21q21q was due to an isochromosome, and not to a translocation.

PMID- 1981471
TI  - Jellyfish envenomation: a summer epidemic.
AB  - During the summer of 1987 the shores of Israel were infested by waves of
      jellyfish. Thirty patients, mainly children, suffering various degrees of painful
      injuries to different parts of their bodies were treated in our emergency ward. A
      typical case is reported and the appropriate treatment recommended.

PMID- 1981473
TI  - Study of the origin of nondisjunction in a family with two cases of Down syndrome
      using cytogenetic and molecular polymorphisms.
AB  - We analyzed the possibility of inherited predisposition to nondisjunction in a
      family with two cases of Down syndrome using restriction fragment length
      polymorphisms and cytogenetic heteromorphisms. In both patients the extra
      chromosome 21 was the result of a nondisjunction event at first meiotic division
      in the mother. Since both patients are maternally related, genetic predisposition
      cannot be excluded in this family.

PMID- 1981474
TI  - Crossing over and chromosome 21 nondisjunction: a study of 60 families.
AB  - To test the hypothesis that meiotic nondisjunction may be caused by reduced
      chiasma frequency, hence recombination, we investigated 60 families with a
      trisomic child affected with Down syndrome (DS). We analyzed cytogenetic
      heteromorphisms (CH) and a number of restriction fragment length polymorphisms
      spanning regions 11.1 through 22.3 of 21q in both parents, in the DS child and,
      when available (21 families), in a normal sib. The parental origin and meiotic
      stage of nondisjunction were determined by combining the results of both CH and
      RFLP analysis. Crossover events were detected as switches in the parental
      haplotype expected in both DS and normal sibs. Available recombination frequency
      data were used to calculate the expected number of crossover events in
      nondisjoined and in normally segregating chromosomes, given the allele
      combination present in each family. The observed number of crossover events in
      normal meioses and in second-division nondisjunctions were consistent with the
      calculated figures. However, a significant reduction in the observed number of
      crossover events was found in nondisjoined chromosomes derived from errors in the
      first meiotic division and, in particular, in the proximal portion of 21q.

PMID- 1981475
TI  - Pericentric inversion of chromosome 9: prevalence in 300 Down syndrome families
      and molecular studies of nondisjunction.
AB  - The incidence of Down syndrome (DS) families where one of the parents is an
      heterozygous carrier of pericentric inversion of the heterochromatic region of
      chromosome 9-inv(9) (qh) - was determined in 3 independent groups of 100 families
      each. The total number of 17 such families found in the sample is significantly
      greater than the expected number of 5.73 for a sample of non-DS families of equal
      size. Consequently, the statistical association of the presence of inv (9) (qh)
      in one parent with the birth of a DS offspring, and the correlative 3-fold
      increased risk of a DS child for such families, seem to be demonstrated. A study
      of the origin of nondisjunction, using restriction fragment length polymorphism
      (RFLP) segregation analysis with a sufficient number of chromosome 21 specific
      probes, has provided complete information in 7 of 8 available families. Although
      the statistical interpretation of the results is not straightforward, due to the
      small size of the sample, the observed data do not contradict the assumption that
      the presence of inv (9) (qh) in a parent increases, by a factor of about 3, the
      chance that the offspring will inherit an extra chromosome 21 from that parent.
      Nevertheless, gathering further data appears desirable because stronger evidence
      would have relevance both for clinical implications and for the understanding of
      the function of heterochromatin, particularly with respect to meiotic and mitotic
      processes.

PMID- 1981476
TI  - Nondisjunction of chromosome 21.
AB  - Chromosome heteromorphisms and restriction fragment length polymorphisms were
      used to study the origin of the extra chromosome in 54 trisomy 21 conceptuses.
      The parental origin was determined in 43 cases, with 39 (91%) being maternally
      and 4 (9%) parentally derived. Analysis of recombination demonstrated the
      presence of one or two cross-overs in most cases for which sufficient information
      was available, suggesting that failure to pair/exchange at meiosis I is
      relatively unimportant in the genesis of trisomy 21.

PMID- 1981477
TI  - Papers presented at the Third Phagocyte Discussion Meeting. Bacteria-phagocyte
      interaction. Edinburgh, Scotland, Ul.

PMID- 1981478
TI  - [Lymphocyte subpopulations in periodontal diseases].
AB  - With the use of inmunohistochemists technics, is possible to determine the
      lymphociter quotient T helps/T suppresers as the proportion of cells that
      expresses molecules DR in its membrane in patients affected on various degrees of
      gingivitis/periodontitis. The results demonstrates the non existence of a
      significative relation between the quotient valnes and the damage degrees. It mas
      observed an incremention the number of cells that had got histocompatibility
      molecules DR in its surface as the degree of damage increased.

PMID- 1981480
TI  - [VII Congress of the Spanish Society of Parenteral and Enteral Nutrition. Palma
      de Mallorca, 3, 4, 5 May 1990].

PMID- 1981479
TI  - [Experimental cryptorchism in the Wistar rat].
AB  - Experimental cryptorchidism was performed on Wistar rats, fixing the left
      testicle into the peritoneum for a month. Animals under study (84) were divided
      into four groups: control, control treated with hCG, cryptorchid and cryptorchid
      treated with hCG. Cryptorchid testes were biopsied at three, five and eight
      months and all were excised at 12 months. Cellular counts on spermatogonia, young
      and late spermatocytes, Sertoli cells and vacuolized Sertoli cells, together with
      the slough tubular and germinal cell percentage and the tubular diameter, let us
      affirm by means statistical studies (ANOVA, Chi square) that a testes recovering
      is already shown at the age of five months, although this recovering still
      differs from the one shown in the control groups.

PMID- 1981481
TI  - Evidence that the stimulatory effect of neurotensin on dopamine release in rat
      nucleus accumbens slices is independent of dopamine D2-receptor activation.
AB  - Neurotensin (NT, 10(-9) M and 10(-7) M) increased the electrically stimulated
      release of [3H]dopamine (DA) in rat nucleus accumbens slices. This effect was not
      altered by activation of DA D2-receptors with high or low concentrations of
      quinpirole (10(-6) M and 10(-8) M) or blockade of DA D2-receptors with near
      maximal concentrations of sulpiride (10(-6) M and 10(-5) M). The sulpiride
      mediated increase in [3H]DA release and the release induced by NT were additive.
      These results suggest that NT functions independently of DA D2-receptor
      activation to modulate DA release in the nucleus accumbens. NT did not modulate
      the simultaneous release of [14C]acetylcholine.

PMID- 1981482
TI  - Irreversible receptor inactivation reveals differences in dopamine receptor
      reserve between A9 and A10 dopamine systems: an electrophysiological analysis.
AB  - Partial receptor inactivation was used as a tool to examine whether differences
      in receptor reserve exist between the dopamine receptor populations which mediate
      responses of substantia nigra (A9) and ventral tegmental area (A10) dopamine
      neurons to dopamine agonist drugs. The irreversible receptor inactivator, N
      ethoxycarbonyl-2-ethoxy-1,2- dihydroquinoline (EEDQ), was administered to rats
      intraperitoneally at a dose of 6 mg/kg (in an ethanol-water vehicle).
      Approximately 24 h after EEDQ treatments, extracellular, single-unit recording
      experiments were carried out. In the first series of experiments, dose-response
      curves were constructed for the inhibition of A9 and A10 dopamine cell firing by
      intravenous administration of the potent dopamine agonist, R-(-)-N-n
      propylnorapomorphine (NPA). For the A9 dopamine cell group, EEDQ pretreatments
      caused a 3-fold rightward shift in the NPA dose-response curve (ED50S, 0.3 vs 0.8
      micrograms/kg for vehicle- and EEDQ-treated rats, respectively), but there was no
      change in the maximum attainable response (greater than 95% inhibition of cell
      firing). For A10 neurons, the same EEDQ treatments produced a greater rightward
      shift in the dose-response curve to NPA (ED50s, 0.6 vs 5.4 micrograms/kg for
      vehicle- and EEDQ-treated rats), and also depressed the maximum response by about
      25% relative to the control (vehicle) curve. The dose-response curves from each
      region were subjected to Furchgott analysis to determine relative receptor
      occupancy-response relationships for NPA. For the A9 system, a steep, hyperbolic
      occupancy-response plot revealed that a 50% inhibitory response required only 4%
      receptor occupancy, while complete (greater than 95%) inhibition of cell firing
      required about 30% occupancy. This suggests about a 70% receptor reserve for this
      agonist in inhibiting A9 dopamine cell firing. The occupancy-response curve for
      A10 cells was less steep with 50% and maximal (greater than 95%) responses
      occurring when 11 and 70% of receptors were occupied by the agonist, indicating
      only about a 30% reserve for A10 cell responses to NPA. While the level of
      'spare' receptors differed substantially between the two areas, calculated pseudo
      KA values were similar (7.7 micrograms/kg for A9 cells and 5.5 micrograms/kg for
      A10 cells), suggesting no regional differences in receptor affinity. To explore
      where the differences in receptor reserve might reside, a second series of
      studies evaluated the effects of iontophoretically applied dopamine and NPA on
      both cell groups in vehicle- and EEDQ-treated rats.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 1981483
TI  - Activation of brown adipose tissue thermogenesis by chemical stimulation of the
      posterior hypothalamus.
AB  - The posterior hypothalamus (PH) is involved in the generation of behavioral
      thermoregulatory responses, but the importance of the PH in the control of
      autonomic thermoregulatory responses such as heat production in brown adipose
      tissue (BAT) is not well defined. In the present study, selective stimulation of
      PH neurons by local application of the excitatory amino acid glutamate (250 nl of
      1 M solution, unilaterally) caused a sharp, transient increase in interscapular
      BAT (IBAT) and core temperature in urethane-anesthetized rats. This effect was
      blocked by pretreatment with the sympathetic ganglionic blocker, chlorisondamine
      chloride (2 mg/kg) or the beta-adrenergic receptor blocker, propranolol (2
      mg/kg), implicating the involvement of the sympathetic system. The effect of
      intra-PH injection of glutamate on IBAT and core temperatures could be mimicked
      by injection of the gamma-aminobutyric acid (GABA) receptor antagonist,
      bicucullin methiodide (BMI, 50 ng), into the same PH site. This effect of BMI
      could be blocked by co-injection of the GABA(A) receptor agonist, muscimol (25
      ng). Further, BMI co-injection potentiated the effect of intra-PH injection of
      glutamate on IBAT and core temperatures. Conversely, muscimol co-injection
      prevented the stimulatory effect of intra-PH injection of glutamate. Taken
      together, the results indicate that direct chemical stimulation of neurons in the
      PH can activate an autonomic mechanism controlling heat production in BAT.
      Further, they suggest the neural mechanism in the PH mediating this effect is
      tonically inhibited by GABA, as blockade of GABAergic function in the PH produces
      an effect similar to that observed after direct stimulation of PH neurons with
      glutamate.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1981484
TI  - Activation of a brain type Na pump after glutamate excitation of cerebral
      neurons.
AB  - Rat cerebral neurons matured in culture were stimulated with glutamate, and the
      effects of glutamate on the activities of the Na pump isoforms were investigated.
      Glutamate increased the total Na pump activity via a remarkable increase in the
      activity of the brain type (highly digitalis-sensitive) isoform and a slight
      decrease in the common type (weakly digitalis-sensitive) isoform activity. The
      effects of glutamate were produced in response to an enhancement of [Na+]i in the
      neurons, which resulted from passive Na+ influx through glutamate receptor
      mediated cation channels. These results suggest that the Na pump isoforms in
      neurons differ in their physiological significance and that the brain type
      isoform plays an important role in restoring concentration gradients of Na+ and
      K+ after neuronal excitation.

PMID- 1981485
TI  - Effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in goldfish brain.
AB  - The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which
      selectively damages dopaminergic neurons in mammals, caused a marked depletion of
      tyrosine hydroxylase (TH) immunoreactivity in the goldfish brain. The concomitant
      ultrastructural observations showed the neurotoxic effect of MPTP on
      telencephalic, diencephalic and medullar neurons. The affected neurons revealed
      darkening of the cytoplasm and swelling of the mitochondria and the endoplasmic
      reticulum. Concomitant significant decreases in dopamine (DA) and noradrenaline
      (NA) levels were determined in the brain areas where morphological observations
      were performed. The loss of catecholamine levels was completely prevented by the
      treatment with the monoamine oxidase (MAO) inhibitor pargyline to prevent MPTP
      oxidation. The results indicate that in goldfish brain, acute MPTP administration
      causes selective catecholamine depletion, without altering the serotoninergic
      system.

PMID- 1981486
TI  - tGS ganglioside induces peculiar morphological features in grafted dopaminergic
      cells and promotes motor recovery in rats with unilateral lesions in the
      nigrostriatal dopamine pathway.
AB  - A cell suspension of substantia nigra from fetal rats was introduced into the
      ipsilateral caudate nucleus of rats with unilateral lesions in the nigrostriatal
      dopamine pathway, and effects of bovine total ganglioside (tGS) and
      monosialoganglioside (GM1) treatment on the morphological features of the
      transplanted cells and recovery from motor imbalance (rotation induced by
      methamphetamine) were investigated. Gangliosides (30 mg/kg) were administered
      intraperitoneally once a day for 2 weeks after transplantation to test animals
      while control animals received saline alone. tGS animals showed definite motor
      recovery in the 2nd week (P less than 0.05) while control and GM1 animals
      exhibited slight recovery only. At 6 weeks after transplantation, motor imbalance
      disappeared in all 3 groups. Tyrosine hydroxylase (TH) immunocytochemical
      staining revealed that in the 2nd week TH-positive cells in tGS animals had more
      primary dendrites and more large neurites (meganeurites) than did controls. TH
      positive cells of all 3 groups often had spiny processes at that time. In the
      20th week, TH-positive cells became more multigonal and had wider dendritic
      fields in all groups, and had less meganeurites and spines. Motor recovery of
      each animal was dependent on the number of TH-positive cells and no significant
      difference was observed in the number of TH-positive cells among the three
      groups. tGS treatment for 2 weeks without grafting induced immunohistologically
      no axonal sprouting in the substantia nigra, medial forebrain bundle, accumbens
      and caudate nucleus when the chemical lesions were complete. Data suggest that
      tGS induces hypertrophy but not hyperplasia of the transplanted nigral cells, and
      increases the morphological plasticity. This might be the basis for promotion of
      recovery in motor function after transplantation.

PMID- 1981487
TI  - Effects of antibodies to dynorphin A and beta-endorphin on lateral hypothalamic
      self-stimulation in ad libitum fed and food-deprived rats.
AB  - Many laboratories have reported that systemically administered naloxone has
      little or no effect on lateral hypothalamic self-stimulation (LH ICSS). In the
      present study, lateral ventricular infusion of beta-endorphin antiserum and a
      high dose of naloxone (100 micrograms) produced small but significant increases
      in stimulation frequency threshold for LH ICSS. beta-Endorphin activity, mediated
      by a non-mu (e.g. delta or epsilon) receptor, may therefore be involved in the
      reinforcement of self-stimulation behavior. When rats are deprived of food for 24
      h, LH ICSS thresholds decline. Under this condition, systemic naloxone elevates
      the LH ICSS threshold, often returning it to the pre-deprivation level. In the
      present study, lateral ventricular infusion of dynorphin A(1-13) antiserum
      similarly reversed the threshold-lowering effect of food deprivation. The effects
      of systemic naloxone and intraventricular dynorphin A antiserum on LH ICSS, which
      are specific to food-deprived animals, may be related to previous findings that
      these two treatments elevate LH stimulation threshold for eliciting feeding
      behavior. Results of the ICSS and stimulation-induced feeding studies suggest a
      model for the mediation of incentive stimuli by dynorphin A activity that is
      afferent to LH 'reward' neurons and positively gated by 'hunger'. An hypothesized
      role for 'hunger'-gated dynorphin A release in potentiating the hedonic response
      to alimentary stimuli and drugs of abuse is discussed.

PMID- 1981488
TI  - Long-term survival of grafted cells, dopamine synthesis/release, synaptic
      connections, and functional recovery after transplantation of fetal nigral cells
      in rats with unilateral 6-OHDA lesions in the nigrostriatal dopamine pathway.
AB  - In animal models of hemi-Parkinson's disease, survival of grafted nigral cells,
      their synaptic connections, dopamine (DA) synthesis/release, and recovery from
      motor disturbances were investigated, and these were compared among 3 groups of
      animals raised for 3 months, 1 year and 2 years after the transplantation. Fetal
      nigral DAergic cell suspensions were transplanted in the ipsilateral caudate
      nucleus of rats with unilateral 6-OHDA lesions in the nigrostriatal DA pathway.
      Motor disturbances, assessed by methamphetamine-induced rotation, recovered
      partly in the 2nd week, significantly in the 4th week after the grafting, and
      remained stable thereafter. Many tyrosine hydroxylase (TH)-positive cells were
      detected along the grafting tracks. The number of TH-positive cells was similar
      in the 3 groups of animals. These TH-positive cells made synaptic connections in
      the host caudate. By in vivo microdialysis measurement, extracellular DA,
      dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) around the grafted
      sites recovered to 30-100% of those of controls. No significant differences were
      observed in the concentration of DA, DOPAC and HVA among 3 groups of animals.
      They also responded to methamphetamine loading though the magnitudes were
      smaller. Using a TH cDNA probe, TH-positive cells were found to express TH mRNA
      in in situ hybridization-autoradiographic analysis. Data indicate that grafted
      fetal DAergic cells survive, synthesize and release DA, make synaptic connections
      in the host brain and ameliorate motor disturbances for over 2 years. There were
      no differences in these parameters among the 3 groups of animals, and no untoward
      side effects were observed even at 2 years after the grafting. Thus it was
      confirmed that the grafting of neuronal cells into the brain is a promising
      approach to restore disturbed function.

PMID- 1981489
TI  - Central somatostatin: a re-examination of its effects on feeding.
AB  - Previous investigations of centrally administered somatostatin (SRIF) have tended
      to employ pharmacological (nmol and greater) doses of the peptide. Under this
      protocol contradictory findings of feeding effects have been reported. There is
      evidence that the use of physiological doses can induce a completely distinct
      response from that obtained with pharmacological doses. In order to discern
      whether physiological doses of centrally administered somatostatin have any
      effect on feeding. SRIF in doses ranging from 0.4 pmol to 3 nmol were
      administered into the lateral ventricles of rats. Low pmol doses (0.4-40)
      administered during the light photoperiod increased 1 h feeding whereas 3 nmol
      decreased 1 h feeding. None of the doses tested during the dark photoperiod
      significantly altered 1 h food intake. Similarly, no significant change in 24-h
      food intake was observed following injections of any of the doses tested, whether
      in the light or dark. A dose of SRIF that increased feeding (1 pmol) did not
      significantly alter 1 h water intake when applied centrally in the light nor did
      it alter spontaneous locomotor activity. Furthermore, when applied peripherally
      it did not change 1 h food intake. These studies suggest that SRIF may work
      centrally to regulate food intake. A similarity exists between SRIF's feeding
      effects and the feeding effects we have previously described following central
      injections of growth hormone-releasing factor (GRF), both in terms of dose
      response and photosensitivity. This suggests that these 2 peptides may act via a
      common mechanism to regulate food consumption; possibly in co-ordination with
      their regulation of growth hormone release. The possibility that such feeding
      regulation occurs as part of a short intrahypothalamic feedback loop is
      discussed.

PMID- 1981490
TI  - Developing neural crest cells in culture: correlation of cytochrome oxidase
      activity with SSEA-1 and dopamine-beta-hydroxylase immunoreactivity.
AB  - This study examines possible changes in energy demands by developing neural crest
      cells in vitro using cytochrome oxidase (C.O.) histochemistry and
      immunohistochemical labeling of adrenergic (autonomic) cells and primary sensory
      neurons. Cytochrome oxidase is a key enzyme for oxidative metabolism and energy
      production, and it is used as a sensitive metabolic marker for neurons in the
      brain and dorsal root ganglia. In primary neural crest cell cultures, C.O.
      staining intensities differ among 4 distinct cellular populations (sensory
      neurons, adrenergic cells, pigment cells, and non-neuronal neural crest cells).
      At all stages, pigment cells exhibit extremely low C.O. staining. Neurons (both
      primary sensory and adrenergic cells) have higher C.O. activity than other cell
      types such as non-neuronal neural crest cells. This indicates that neurons have
      higher energy demands and presumably higher levels of functional activity than
      other cell types at least under the present culture conditions. All neurons in
      neural crest cell cultures elevate their energy demands during development,
      implying that energy metabolism and functional activity increase with neuronal
      maturation. At all stages, early determined sensory neurons exhibit more intense
      C.O. staining than late-developing sensory neurons. The difference in C.O.
      activity between the two populations of sensory neurons may be caused by
      different levels of functional activity due to their different time course of
      development. Tetrodotoxin (TTX) at 0.5-1 microM concentrations causes a decrease
      in the level of C.O. activity in the early determined sensory neurons, which may
      be correlated with a decrease in the functional activity of these neurons. Triple
      staining combining C.O. histochemistry with indirect immunofluorescence of
      antibodies against the stage specific embryonic antigen-1 (SSEA-1, which labels
      quail sensory neurons) and dopamine-beta-hydroxylase (DBH, which labels
      adrenergic cells) distinguish the level of C.O. activity between sensory neurons
      and autonomic cells. DBH+ cells exhibit relatively low C.O. staining. However,
      the C.O. activity among SSEA-1+ neurons varies from high to low levels. In
      general, SSEA-1+ sensory neurons are much more C.O. reactive than DBH+ autonomic
      cells. This suggests that developing sensory neurons in culture may have higher
      spontaneous and/or synaptic activity than autonomic neurons.

PMID- 1981492
TI  - Selective beta-1-adrenoceptor partial agonist treatment for congestive heart
      failure.
AB  - Xamoterol is a beta-adrenoceptor partial agonist which selectively acts at the
      beta 1-receptors of the heart. The partial agonist effect modestly increases
      myocardial contractility and appears also to improve diastolic function and
      cardiac output without an increase in myocardial oxygen demand. Improved
      myocardial performance is maintained during exercise while increased heart rate
      is attenuated. Partial agonist activity protects against tachyphylaxis and
      arrhythmogenicity. With chronic treatment, exercise duration and work capacity
      increase and clinical manifestations of heart failure are reduced.

PMID- 1981491
TI  - Regression of left ventricular hypertrophy in patients with essential
      hypertension: outcome of 12 years antihypertensive treatment.
AB  - To assess the regression of cardiac hypertrophy during long-term (12 years)
      antihypertensive treatment, the following parameters were determined in 93
      patients with essential hypertension: SV1 + RV5 by electrocardiography (ECG), and
      septal wall (SW) and posterior wall (PW) thickness by echocardiography (UCG). The
      patients were treated with a thiazide diuretic alone (group 1), thiazide + beta
      blocker (group 2), thiazide + methyldopa or nifedipine (group 3) or nifedipine or
      methyldopa alone (group 4). The blood pressure decreased gradually within 6
      months of treatment. According to ECG, regression of left ventricular hypertrophy
      occurred during the initial 7 years in all groups, whereas in the subsequent 5
      years, statistically significant regression was found only in the patients
      treated with thiazide + other drugs (group 3). By UCG, which was taken only at
      the 7th and 12th year, regression was detectable during the last 5 years in all
      groups. The apparent incidence of regression of hypertrophy was lower in the
      thiazide-alone group (group 1) than in the thiazide + beta-blocker group (group
      2), most likely due to mild hypertension in group 1. A cardiovascular accident
      (nonfatal myocardial infarction) occurred only in 1 patient. We conclude that
      during long-term antihypertensive treatment, persistent, progressive reversal of
      cardiac hypertrophy takes place.

PMID- 1981493
TI  - Bopindolol for the treatment of chronic stable angina pectoris--a clinical study
      of the relationship between dose and effect.
AB  - Following a 4-week placebo period, 19 patients (12 male, average age 62.3 years)
      with chronic stable angina pectoris and a positive exercise test were treated
      with the beta-adrenoceptor antagonists bopindolol at increasing doses of 0.5, 1
      and 2 mg, each being given once daily for 4 weeks. For the final 4 weeks of the
      study, active treatment was replaced by placebo. Maximum tolerated exercise
      (bicycle ergometry, performed 24 h after drug administration) increased dose
      dependently from 519 +/- 59 s (baseline) to 758 +/- 95 s with 2 mg (p less than
      0.001) and fell again to 508 +/- 48 s (placebo). The frequency of anginal attacks
      also fell dose-dependently from an average of 5.4 per week (baseline) to 0.5 with
      2 mg (p less than 0.001) and rose again to 5.1 per week when active treatment was
      stopped.

PMID- 1981494
TI  - Preprotachykinin A mRNA expression in the rat brain during development.
AB  - Expression of preprotachykinin A (PPT-A) mRNA was analyzed by northern blots
      using mRNA prepared from rat brain at 12 different developmental stages ranging
      from embryonic day 15 (E15) to adult. A single PPT-A mRNA of 1.3 kb was detected
      throughout development. PPT-A mRNA was detected as early as E15 and an
      approximately 3-fold increase occurred at birth. This amount remained until 3
      weeks of age when the level increased, reaching a peak at 5 weeks of age. Adult
      amounts were approximately 3-fold higher than the levels at birth. The
      distribution of PPT-A mRNA-expressing cells in rat brain was studied by in situ
      hybridization on sections from embryonic day 20, postnatal days 4 and 7 as well
      as adult. Cells expressing PPT-A mRNA were detected in the forebrain at all 4
      ages analyzed. However, the hybridization pattern and the labeling intensity
      varied in different brain regions during development. In cingulate cortex,
      intense labeling was seen in numerous cells at embryonic day 20 and postnatal
      days 4 and 7, whereas in the adult cingulate cortex only a few scattered labeled
      cells were observed. In frontoparietal cortex labeled cells were found from
      postnatal day 4 to adult, with the highest density of labeled cells at P7.
      Developmental differences in both the distribution of PPT-A mRNA-expressing cells
      and the level of PPT-A mRNA expression were also found in caudate-putamen,
      lateral hypothalamus and amygdala. Thus, our results show several changes in PPT
      A mRNA expression during ontogeny, indicating a region and time-specific
      regulation of PPT-A mRNA expression during brain maturation.

PMID- 1981496
TI  - Contact dermatitis. An international symposium. 17-19 May 1990, Stockholm,
      Sweden.

PMID- 1981497
TI  - The role of MHC class II genes in susceptibility to insulin-dependent diabetes
      mellitus.

PMID- 1981495
TI  - The effect of prenatal exposure to methadone on neurotransmitters in neonatal
      rats.
AB  - The effect of prenatal exposure to methadone via maternal osmotic minipumps was
      studied on neurotransmitter content of 4-day-old male and female rats. Several
      sex-related differences were observed in brain regional neurotransmitter content.
      Prenatal exposure to methadone produced only selective changes in brain regional
      neurotransmitter content. Exposure to methadone in doses sufficient to produce
      maternal and fetal dependence selectively reduced striatal acetylcholine content
      and produced a sex-dependent change in hindbrain acetylcholine.

PMID- 1981498
TI  - Relative predispositional effect of a PADPRP marker allele in B-cell and some non
      B-cell malignancies.

PMID- 1981499
TI  - Human gene mapping 10.5. Oxford Conference (1990). Update to the Tenth
      International Workshop on Human Gene Mapping.

PMID- 1981500
TI  - Report of the committee on the genetic constitution of chromosome 19.

PMID- 1981501
TI  - Report of the committee on the genetic constitution of chromosome 20.

PMID- 1981502
TI  - Report of the committee on the genetic constitution of chromosome 22.

PMID- 1981503
TI  - Report of the committee on human mitochondrial DNA.

PMID- 1981504
TI  - The 1990 catalog of mapped genes and report of the nomenclature committee.

PMID- 1981505
TI  - Quinolone inhibition of cytochrome P-450-dependent caffeine metabolism in human
      liver microsomes.
AB  - Inhibitory effects of the quinolone antibiotics ofloxacin, lomefloxacin,
      pipemidic acid, ciprofloxacin, and enoxacin on caffeine metabolism were examined
      in vitro with human liver microsomes of four donors. All drugs competitively
      inhibited the activity of 3-demethylation, the major pathway of caffeine
      metabolism. Enoxacin, ciprofloxacin, and pipemidic acid were strong inhibitors
      exhibiting Ki values between 0.1 and 0.2 mM. Lomefloxacin and ofloxacin had
      moderate effects with Ki values of 1.2 and 3.6 mM, respectively. The rate of
      caffeine 7-demethylation (which amounted to about 25% of that for 3
      demethylation) was only slightly affected by the quinolones. Minor, but
      inconsistent, effects were found on 8-oxidation to 1,3,7-trimethyluric acid. The
      results indicate that the reduction of caffeine clearance by concomitant
      quinolone application observed in vivo is primarily due to a competitive
      interaction of the inhibiting quinolones with the cytochrome P-450 isoenzyme(s)
      mediating caffeine demethylation.

PMID- 1981507
TI  - Plasma elimination and urinary excretion of methapyrilene in the rat.
AB  - The metabolism and elimination of methapyrilene (2-[(2-dimethylaminoethyl)-2
      thenylamino]pyridine) were characterized after the iv administration of 0.7 mg/kg
      or 3.5 mg/kg methapyrilene HCl plus [14C]methapyrilene HCl to adult male Fischer
      344 rats. Approximately 40% and 35% of the administered dose was excreted in the
      urine in the first 24 hr in the low and high dose groups, respectively, as
      determined by liquid scintillation spectrophotometry. Fecal excretion accounted
      for 38% and 44% of the administered dose in the first 24 hr in the low and high
      dose groups, respectively, as confirmed via combustion analysis. The 24-hr
      urinary metabolic products consisted of one major and five minor radiolabeled
      compounds. The major metabolite was isolated with reversed-phase HPLC and
      identified as methapyrilene N-oxide. This was accomplished by comparison of the
      chromatographic and mass spectral characteristics of this metabolite with that of
      authentic methapyrilene N-oxide. Methapyrilene and mono-N-desmethyl methapyrilene
      also were identified after isolation with reversed-phase HPLC and comparison of
      their mass spectral and/or chromatographic properties with those of authentic
      compounds. The plasma metabolic profile was essentially the same as the urinary
      profile. The elimination of methapyrilene from plasma occurred through a first
      order process. The terminal plasma elimination t1/2 of methapyrilene did not
      increase with increasing doses (2.75 hr, 0.7 mg/kg; 2.81 hr, 3.5 mg/kg); thus,
      methapyrilene does not exhibit dose-dependent elimination over this 5-fold dose
      range.

PMID- 1981506
TI  - Pulmonary elimination and metabolism of 5-fluoro-2'-deoxyuridine in isolated
      perfused rat lung and lung slices.
AB  - Elimination kinetics and metabolism of the cytostatic drug 5-fluoro-2'
      deoxyuridine (FUDR) were studied in isolated perfused rat lung and in incubated
      lung slices. The intact organ exhibited a low clearance of 0.2 to 0.8 ml/min and
      a calculated first-pass extraction of 2 to 7% of the drug inflow. Thus, the
      pulmonary uptake of the fluorinated nucleoside from the circulation is low.
      Within 120 min of perfusion, however, 30 to 45% of the initial FUDR dose was
      metabolized by the isolated rat lung. The nucleobase metabolite 5-fluorouracil
      (FU) represented almost all FUDR metabolites in the medium, indicating that this
      metabolic pathway, mediated by thymidine phosphorylase, is active in lung while
      the enzymic activity for further pyrimidine degradation is low. This was
      demonstrated in incubated lung slices, which have a high capacity to transform
      FUDR into FU, comprising 83 to 95% of the metabolites in the medium. The final
      catabolic metabolite, alpha-fluoro-beta-alanine, was present in trace amounts
      only. It is concluded that the pulmonary tissue contains a marked "intrinsic"
      capacity to transform FUDR into FU, while the metabolic activity for catabolism
      of the nucleobase metabolites FU and 5,6-dihydrouracil is virtually lacking.

PMID- 1981508
TI  - Metabolism of antiparkinson agent dopazinol by rat liver microsomes.
AB  - Metabolism of dopazinol (DZ) by liver microsomes from control and phenobarbital-
      and 3-methylcholanthrene-treated rats has been investigated. Liver microsomes
      from control and treated rats metabolized DZ to N-despropyl-DZ (39-53% of total
      metabolites); 8-hydroxy-DZ, a catechol metabolite (32-39%); and 5- or 6-hydroxy
      DZ (12-20%). The last metabolite was identified as its dehydration product 5,6
      dehydro-DZ. N-Dealkylation was favored only slightly over catechol formation
      (ratio = 1.2) by liver microsomes from control and phenobarbital-treated rats,
      whereas with liver microsomes from 3-methylcholanthrene-treated rats, N
      dealkylation predominated (ratio = 1.7). Liver microsomes from control rats
      metabolized DZ at a rate of 0.86 nmol/nmol cytochrome P-450/min. Pretreatment of
      rats with phenobarbital or 3-methylcholanthrene stimulated rates of metabolism by
      2.4- and 3-fold, respectively. Metabolism of DZ was inhibited by SKF 525-A,
      methimazole, and thiobenzamide. SKF 525-A completely inhibited metabolism of DZ,
      while methimazole and thiobenzamide, two alternate substrates of the microsomal
      flavin-containing monooxygenase (MFMO) inhibited N-dealkylation only. These
      results indicated that while the cytochrome P-450-dependent monooxygenase is the
      primary enzyme system in DZ oxidation, the MFMO also catalyzes the N-dealkylation
      reaction. The catechol metabolite was converted to isomeric O-methylated
      derivatives in approximately 1:1 ratio by purified catechol-O-methyl transferase
      or 105,000g liver cytosol. The late eluting isomer was 8-methoxy-DZ.

PMID- 1981509
TI  - Three N-aralkylated derivatives of 1-aminobenzotriazole as potent and isozyme
      selective, mechanism-based inhibitors of guinea pig pulmonary cytochrome P-450 in
      vitro.
AB  - The potency and cytochrome P-450 (P-450) isozyme selectivity of 1
      aminobenzotriazole (ABT) and three of its N-aralkylated analogues, N-benzyl-1
      aminobenzotriazole (BBT), N-alpha-methylbenzyl-1-aminobenzotriazole (alpha MB),
      and the newly synthesized N-alpha-ethylbenzyl-1-aminobenzotriazole (alpha EB), as
      mechanism-based inhibitors were compared in pulmonary microsomes of untreated and
      beta-naphthoflavone (beta-NF)-induced guinea pigs. All four compounds were
      suicide substrates for pulmonary P-450, resulting in the loss of spectrally
      assayed hemoprotein (up to 50%). Monooxygenase activities were measured with
      isozyme-selective/specific substrates; the O-dealkylation of 7-pentoxyresorufin
      (PRF) for the guinea pig ortholog of rabbit P-450IIB4, the O-deethylation of 7
      ethoxyresorufin for P-450IA1, and the N-hydroxylation of the aromatic amine 4
      aminobiphenyl for P-450IVB1, BBT, alpha MB, and alpha EB were selective for the
      suicidal inhibition of P-450IIB4; for example, 1 microM alpha MB inactivated 95%
      of P-450IIB4-, and approximately 10% of P-450IA1- and IVB1-catalyzed, activity in
      microsomes from beta-NF-induced lungs. Isozyme selectivity was approximately the
      same for alpha EB and slightly lower for BBT, which inactivated relatively more P
      450IA1. At low concentrations, 1 and 10 microM, respectively, ABT preferentially
      inactivated P-450IVB1, consistent with the efficient N-hydroxylation of aromatic
      amines by this form of P-450. alpha EB also was shown to efficiently inactivate P
      450IIB4-catalyzed PRF activity in microsomes prepared from liver of phenobarbital
      induced guinea pigs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1981510
TI  - Formation and reversibility of S-linked conjugates of N-(1-methyl-3,3
      diphenylpropyl)isocyanate, an in vivo metabolite of N-(1-methyl-3,3
      diphenylpropyl)formamaide, in rats.
AB  - The metabolic disposition of N-(1-methyl-3,3-diphenylpropyl) formamide was
      studied in rats. The water-soluble metabolites, N-acetyl-S-[N-(1-methyl-3,3
      diphenylpropylcarbamoyl)]cysteine and S-[N-(1-methyl-3,3
      diphenylpropylcarbamoyl)]glutathione, were identified in urine and bile,
      respectively, of rats doses with the secondary formamide. The structures of these
      metabolites were confirmed by comparison with synthetic standards and by using
      liquid chromatography mass spectrometry and fast atom bombardment mass
      spectrometry. Synthetic standards of these metabolites were obtained by reacting
      the N-(1-methyl-3,3-diphenylpropyl)isocyanate with glutathione or N
      acetylcysteine in methanolic solutions. The isocyanate was obtained in high yield
      by reacting 1-methyl-3,3-diphenylpropylamine with trichloromethyl chloroformate.
      The S-linked conjugates released the isocyanate in mild alkali, but were stable
      under acidic conditions. The released isocyanate was characterized by comparison
      with the synthetic standard using GC/MS and HPLC. A mechanism is proposed for the
      base-catalyzed elimination of the isocyanate from the thiol conjugates.

PMID- 1981511
TI  - In vitro metabolism of (-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl) phenyl]-trans
      4-(3-hydroxypropyl) cyclohexanol, a synthetic bicyclic cannabinoid analog.
AB  - The oxidative metabolism of CP-55,940 [(-)-cis-3-[2-hydroxy-4-(1,1
      dimethylheptyl)phenyl]-trans-4-(3- hydroxypropyl)cyclohexanol] was studied in
      mouse liver S-9 microsomal preparations. [3H]CP-55,940 was incubated in a
      microsomal supernatant enriched with the appropriate cofactors for cytochrome P
      450 oxidative metabolism. HPLC separation of petroleum ether/diethyl ether (1:1)
      extracts facilitated the identification of metabolites by GC/MS after
      derivatization with BSTFA or [2H18]BSTFA. The mass spectral data indicated that
      five monohydroxylated metabolites had been formed that differed with respect to
      the position of hydroxylation on the 1',1'-dimethylheptyl side chain. Two
      additional compounds were detected whose mass spectral data suggested that these
      metabolites were hydroxylated at two positions on the side chain. Side chain
      hydroxylation is consistent with the metabolic profile of delta 9
      tetrhydrocannabinol (delta 9-THC) and other cannabinoid compounds. It is possible
      that these side chain-hydroxylated metabolites retain activity, as is the case
      with similar metabolites formed from delta 9- and delta 8-THC, and thereby
      contribute to the pharmacological profile seen with this potent synthetic
      cannabimimetic agent.

PMID- 1981512
TI  - Species comparison of pharmacokinetics and metabolism of diltiazem in humans,
      dogs, rabbits, and rats.
AB  - Diltiazem (DTZ) is a calcium antagonist widely used in the treatment of angina
      and related heart diseases. It is extensively metabolized into a host of
      metabolites, some of which have potent pharmacological activities. In this study,
      the pharmacokinetics and metabolism of DTZ was investigated in humans, dogs,
      rabbits, and rats after each species (n = 4 or 5) was given a single oral dose of
      DTZ. After the drug administration, blood and urine samples were collected for 12
      and 48 hrs, respectively. DTZ and six of its metabolites were quantitated in our
      laboratory by HPLC. The results indicated that, in humans, the major metabolites
      in plasma were N-monodesmethyl diltiazem (MA), deacetyl diltiazem (M1), and
      deacetyl N-monodesmethyl diltiazem (M2). These metabolites were also detected in
      the plasma of dogs, rabbits, and rats. However, there were quantitative
      differences. For example, in the humans and dogs, MA was the most abundant
      metabolite in plasma, while M1 and M2 were most prominent in the rabbits and
      rats, respectively, and M2 was a relatively minor metabolite in dog plasma. Less
      than 5% of the dose was recovered as unchanged DTZ in the urine of all the tested
      species. The most abundant metabolites in urine appeared to be MA and deacetyl
      N,O-didesmethyl diltiazem, although there were considerable inter- and intra
      species variations. Two additional metabolites were detected in the urine of the
      humans, dogs, and rabbits, but not in the rats. They were tentatively identified
      as O-desmethyl diltiazem and N-O-didesmethyl diltiazem, using electron impact and
      ammonia chemical ionization mass spectrometry.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1981513
TI  - Pharmacokinetics of flobufen and its main active metabolite in the rat.
AB  - Pharmacokinetic study of the anti-inflammatory [3H] flobufen (I) and its active
      metabolite (II) has been carried out in rats given po and iv doses of 2, 10, and
      50 mg/kg I and equimolar doses of II. Various pharmacokinetic parameters of I and
      II [dose normalized AUC; mean residence time (MRT); systemic blood clearance;
      steady state volume of distribution, (Vss)] are dose-independent. I is completely
      absorbed from the gastrointestinal tract and is rapidly (MRT = 7.2 hr) converted
      to II, which is slowly (MRT = 2.6 days) eliminated from the blood. The fraction
      of total blood clearance that forms II is 0.83 following iv dose of I. The Vss of
      the less lipophilic metabolite II is somewhat lower (0.36-0.46 liters/kg) than
      that of the parent drug (0.51-0.56 liters/kg).

PMID- 1981515
TI  - Systemic pharmacokinetics of acetylenic retinoids in rats.
AB  - In order to widen the therapeutic index of retinoids, one approach is to
      synthesize retinoids with reduced systemic distribution. Sixteen acetylenic
      retinoids were evaluated for their systemic disposition kinetics in rats after iv
      doses. Four pharmacokinetic parameters (i.e., total body clearance, volume of
      distribution at steady state, mean residence time, and the elimination half-life)
      were calculated for all retinoids tested. These compounds were categorized into
      four groups according to their functional head group. Retinoic acids having the
      trimethylcyclohexenyl head group as isotretinoin most mimicked isotretinoin in
      disposition profiles among all retinoic acids examined. They had volumes of
      distribution similar to and mean residence times shorter than those of
      isotretinoin. Retinoic acids containing the tetramethyltetralinyl head group as
      arotinoid had extensive tissue distribution and small body clearance. They had
      extended elimination half-lives similar to those observed for etretinate.
      Dimethylchromanyl and dimethylthiochromanyl retinoic acids were more polar; their
      terminal half-lives were reasonably short and no extensive tissue distribution
      was noted. The ethyl retinoates rapidly converted to their corresponding retinoic
      acids after iv doses. All ethyl esters had limited systemic residence times. The
      ethyl nicotinates tended to have much larger body clearance (10- to 25-fold) than
      the ethyl benzoates. After iv administration of ethyl retinoates, the ethyl
      esters disappeared rapidly, while their corresponding retinoic acids became the
      major drug-derived species in blood. The study results demonstrated different
      pharmacokinetic behaviors of acetylenic retinoids with different functional head
      groups.

PMID- 1981514
TI  - In vitro metabolism of cannabichromene in seven common laboratory animals.
AB  - Metabolism of cannabichromene (CBC) was studied in hepatic microsomal incubates
      from mouse, rat, rabbit, guinea pig, cat, hamster, and gerbil. Metabolites were
      extracted with ethyl acetate, concentrated by chromatography on Sephadex LH-20,
      and identified by GC/MS as trimethylsilyl derivatives of both the metabolites
      themselves and their hydrogenated analogues. Thirteen metabolites were
      identified. The major metabolites were monohydroxy compounds with hydroxylation
      at all positions of the pentyl and methylpentenyl chains. An epoxide and its
      derived dihydrodiol were formed from the double bond in the methylpentenyl
      chains. Several unidentified decomposition products were found in the extracts
      from mouse, gerbil, and cat; these appeared to have been produced by the opening
      of the dihydropyran ring. Metabolism varied considerably between the species,
      although the trans-hydroxy metabolite 5'-hydroxy-CBC was the major metabolite in
      most cases. Metabolites hydroxylated in the pentyl chain were more abundant in
      mouse, rabbit, and cat; the hamster, gerbil, and cat produced the most epoxide
      derived material.

PMID- 1981516
TI  - The pharmacokinetics of (-)-carbovir in rats. Evidence for nonlinear elimination.
AB  - This study evaluated the pharmacokinetics and bioavailability of (-)-carbovir in
      rats following iv and po administration at doses of 10 to 120 mg/kg. The systemic
      clearance decreased 5-fold as the iv dose was increased from 10 to 120 mg/kg. At
      lower doses, (-)-carbovir was eliminated primarily by the renal route. The renal
      component of clearance became saturated as the dose was increased, leading to
      nonlinearity in the pharmacokinetics of (-)-carbovir. There were no changes in
      the metabolic clearance or the formation clearance of the major metabolite over
      the dose range of 10 to 60 mg/kg. The clearance value estimated following iv
      bolus administration was a "concentration averaged" value, and was not predictive
      of the steady-state concentrations. IV infusion studies indicated that at plasma
      concentrations less than 2500 ng/ml, the pharmacokinetics of (-)-carbovir were
      linear. The bioavailability was calculated for each treatment level and ranged
      from 43% at 10 mg/kg (iv and po) to 3% at 120 mg/kg (iv and po). The nonlinearity
      in the pharmacokinetics of (-)-carbovir must be taken into account when
      determining the bioavailability. At doses lower than 10 mg/kg, where the serum
      concentrations after iv administration would always remain in the linear range,
      the bioavailability may approach 50 to 60%. Poor bioavailability at high doses in
      the rat may not be reflective of the clinical situation, since the anticipated
      doses will be much lower than those administered in the rat.

PMID- 1981518
TI  - Identification of a glucuronide conjugate of the carbocyclic nucleoside,
      carbovir, isolated from marmoset urine.

PMID- 1981517
TI  - The metabolism and excretion of carbovir, a carbocyclic nucleoside, in the rat.
AB  - The metabolism and disposition of carbovir [(1R-cis)-2-amino 1,9-(4
      (hydroxymethyl)-2-cyclopenten-1-yl)-6H-purin-6-one], an antiviral agent, was
      examined in rats using an isolated perfused liver, and in vivo following iv and
      po administration at two dosing levels. HPLC analysis of perfusate and bile after
      perfusion of the isolated liver with racemic (+/-)[8-3H]carbovir showed
      conversion to two major metabolites. The major component in the bile was shown to
      be a glucuronide conjugate of carbovir. The perfusate contained a single major
      component that was isolated and identified as the 4'-carboxylic acid derivative.
      In vivo excretion balance studies were conducted with [8-14C](-)-carbovir using
      four animals in each dosing group. Following iv administration at 10 mg/kg doses,
      the majority of the dose (77%) was excreted in the urine. At 60 mg/kg iv dosing,
      this value dropped to 42% (the remainder appearing in the feces). With po
      administration at both doses, the bulk of the dose (41-61%) was excreted in the
      feces. HPLC profiling of the urine showed that in all cases, most of the
      radioactivity was accounted for as carbovir and the 4'-acid metabolite. This
      metabolite accounted for up to 25% of the administered dose following 60 mg/kg iv
      administration, and less than 3% following 10 mg/kg po dosing. A second urinary
      metabolite accounting for up to 5% of the dose also was seen in all samples. This
      was isolated and identified as the trans-diastereomer of the 4'-acid (resulting
      from epimerization at the 4' position).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1981519
TI  - Identification of phenolic doxepin glucuronides from patient urine and rat bile.

PMID- 1981521
TI  - The metabolism of ofloxacin in humans.

PMID- 1981520
TI  - Characterization of a quaternary, N-glucuronide metabolite of the imidazole
      antifungal, tioconazole.

PMID- 1981522
TI  - The metabolic fate of 13-cis-retinoic acid in mouse skin microsomal preparations.

PMID- 1981523
TI  - The 1988 Bernard B. Brodie Award lecture. Functional diversity of hepatic
      cytochromes P-450.

PMID- 1981525
TI  - Dose-dependent pharmacokinetics of MK-417, a potent carbonic anhydrase inhibitor,
      in rabbits following single and multiple doses.
AB  - MK-417, a potent carbonic anhydrase inhibitor capable of reducing intraocular
      pressure after topical application, is currently under investigation for the
      treatment of glaucoma. The purposes of this study were to characterize dose
      dependent pharmacokinetics of MK-417 and to determine the accumulating effect of
      the drug during chronic topical administration in rabbits. Because the drug
      resided primarily in the erythrocytes, kinetic analyses were performed on whole
      blood concentration data. Following i.v. administration, both total blood
      clearance and apparent volume of distribution for MK-417 increased
      disproportionately between the low and high dose, while the half-life of the drug
      appeared to be independent of dose. Total blood clearance and apparent volume of
      distribution increased from 0.993 +/- 0.224 ml/hr/kg (mean +/- SD) and 88.6 +/-
      9.4 ml/kg at a dose of 0.05 mg/kg to 2.73 +/- 0.17 ml/hr/kg and 272 +/- 5.5 ml/kg
      at a dose of 1 mg/kg. The dose-dependent kinetics of MK-417 are probably due to
      the saturable binding of carbonic anhydrase. Upon instillation of MK-417 into the
      eyes, the drug was rapidly and well absorbed. At the low dose of 0.05 mg/kg, the
      bioavailability varied from 58% to 98.5% with a mean value of 76.5 +/- 20.5%.
      Prediction of concentrations of MK-417 during chronic topical administration were
      performed based on the corresponding concentrations after a single topical dose
      using an overlay technique. Good agreement between the experimental data and the
      predicted blood concentrations of MK-417 during chronic dosing at 0.05 mg/kg, but
      not at 1 mg/kg, strongly suggests that linear kinetics apply in the case of the
      low dose but not in the case of the high dose.

PMID- 1981524
TI  - Pharmacokinetics and tissue distribution of the renin inhibitor N-(2-(R)-benzyl-3
      tert-butyl-sulfonyl-propionyl)-His-ChacVal-n-butylami ne in marmosets.
AB  - The fate of CGP 38 560 [N-(2-(R)-benzyl-3-tert-butyl-sulfonyl-propionyl)-His
      ChacVal-n-bu tylamine], a potent renin inhibitor, has been studied in marmosets.
      [3H]CGP 38 560 is rapidly cleared from the plasma. The elimination process is
      biphasic, with a t1/2 of 4.8 +/- 1.0 min (mean +/- SD) in the first phase and
      26.6 +/- 8.4 min (mean +/- SD) in the second. The kinetics of elimination from
      plasma are similar when measured both in a radio-inhibitor binding assay and
      radiometrically using 3H-labeled substance. The drug is mainly eliminated in the
      bile, almost 73.8% of the i.v. administered dose being excreted within the first
      60 min. It is detectable in bile in both unchanged (8.6%) and metabolized form.
      HPLC analysis of bile extracts showed at least five tritiated peaks representing
      constituents capable of binding human renin (A, B, C, D, and E). These fractions
      were isolated, purified, and analyzed by mass spectrometry. Peak E corresponded
      to unchanged CGP 38 560. Metabolites A, B, C, and D are more polar than the
      parent compound, as indicated by their retention times upon HPLC analysis. The
      metabolic pathways inferable from the respective molecular weights are
      hydroxylation, oxygenation, and, in one case, cleavage of the n-butylamino group
      located at the COOH-terminal. From comparisons of the pharmacokinetic parameters
      after iv (0.1 mg/kg) and oral (10 mg/kg) administration, it can be estimated that
      the bioavailability of CGP 38 560 in the marmoset is 0.3%.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1981526
TI  - Disposition and metabolism of carbovir in mice dosed intravenously or orally.
AB  - To determine the disposition of carbovir and [3H]carbovir in mice, HPLC and thin
      layer chromatographic assays were developed and mice were dosed iv and by gavage.
      Carbovir had no lethal effect at iv doses up to 500 mg/kg and was stable for 24
      hr in mouse plasma at temperatures ranging from 0-37 degrees C. Binding to plasma
      proteins was minimal. Following an iv dose of 500 mg/kg of carbovir or [3H]
      carbovir, elimination phases with half-lives of 26-37 min (alpha) and 206-330 min
      (beta) were observed for plasma. For mice dosed with 27 mg/kg of [3H]carbovir,
      however, only a single phase with a half-life of 17 min was noted. Of several
      tissues examined, kidney contained the highest concentration of radioactivity.
      For the high dose, 19.0 +/- 2.6% was excreted in the urine in 24 hr as unchanged
      carbovir and 42.2 +/- 2.4% as metabolites; for the low dose, 54.5 +/- 6.1% was
      excreted as carbovir and 26.5 +/- 5.0% as metabolites. When mice were dosed
      orally with 500 mg/kg, plasma concentrations of carbovir were low. The initial
      plasma half-life for carbovir was 69 min; the terminal half-life was 822 min.
      Urinary excretion of unchanged carbovir was 21.3 +/- 7.1%. These results indicate
      that clearance of high doses of carbovir is limited and that its absorption is
      poor after oral dosing.

PMID- 1981527
TI  - Disposition of amiodarone and its proximate metabolite, desethylamiodarone, in
      the dog for oral administration of single-dose and short-term drug regimens.
AB  - A comparative study of the plasma disposition and tissue distribution of
      amiodarone and its proximate metabolite, desethylamiodarone, for a single oral
      dose and short-term oral dosage regimens was conducted in the dog. Four groups of
      male mongrel dogs (six per group) received one of the following oral dosage
      regimens: single dose of 40 mg amiodarone/kg; 40 mg amiodarone/kg/day for 10 days
      and then 30 mg/kg/day for 4 days; 40 mg amiodarone/kg/day for 10 days, 30
      mg/kg/day for 4 days, and then no treatment for 14 days; and 40 mg
      amiodarone/kg/day for 10 days, 30 mg/kg/day for 4 days, and then 20 mg/kg/day for
      5 days/week for 2 weeks. The plasma and tissue amiodarone and desethylamiodarone
      concentrations were determined by HPLC. The plasma concentration of amiodarone
      was greater than that of desethylamiodarone for the four dosage regimens. The
      apparent plasma elimination half-life of amiodarone was prolonged following
      repeated drug administration (3.2 days) compared with a single drug dose (7.5
      hr). There was extensive extravascular distribution of amiodarone and
      desethylamiodarone resulting in progressive tissue accumulation of drug and
      metabolite for the short-term regimens. For most of the dosage regimens, the
      concentration of amiodarone was greater than that of desethylamiodarone in left
      and right ventricles, thyroid gland, adipose tissue, and kidney, whereas the
      parent drug and metabolite concentrations were similar in lung, liver, and brain.
      There was predominant accumulation of amiodarone in adipose tissue and
      desethylamiodarone in lung. After cessation of amiodarone administration, there
      was rapid elimination of parent drug and metabolite from all tissues, except for
      amiodarone from adipose tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1981528
TI  - Pharmacokinetics, N1-glucuronidation, and N4-acetylation of sulfa-6-monomethoxine
      in humans.
AB  - Sulfamonomethoxine (S) is metabolized by O-dealkylation, N4-acetylation, and N1
      glucuronidation. In humans, only N1-glucuronidation (12%) and N4-acetylation
      (36%) takes place. The N1-glucuronide is directly measured by HPLC. When N4
      acetylsulfamonomethoxine (N4) is administered as the parent drug, N1
      glucuronidation does not occur. After an oral dose, fast and slow acetylators
      show a similar t1/2 for S (25.0 +/- 4.6 hr vs. 29.8 +/- 4.8 hr; p = 0.459), and
      the t1/2 of the N4-acetyl conjugate is also similar in fast and slow acetylators
      (25.0 +/- 4.64 hr vs. 29.8 +/- 4.8 hr, p = 0.459). The intrinsic mean residence
      time of N4 is 7.1 +/- 2.3 hr. The mean total body clearance of S is 5.0 +/- 1.3
      ml/min, the renal clearance is 0.84 +/- 0.26 ml/min, and the volume of
      distribution at steady state is 11.7 +/- 3.4 liters. The renal clearance of N4 is
      17.89 +/- 4.19 ml/min. No measurable concentrations of the N1-glucuronide of S
      are found in plasma. The protein binding of S is 92%. N1-glucuronidation results
      in an 80% reduction in the protein binding of S (11%). N4 shows a high protein
      binding of 98%. Approximately 60% of the oral dose of S is excreted in the urine.

PMID- 1981529
TI  - Progesterone metabolism in hepatic microsomes. Effect of the cytochrome P-450
      inhibitor, ketoconazole, and the NADPH 5 alpha-reductase inhibitor, 4-MA, upon
      the metabolic profile in human, monkey, dog, and rat.
AB  - Progesterone was incubated in the presence of NADPH with hepatic microsomes
      isolated from male and female human, monkey, dog, and rat and the effect of 17
      beta-NN-diethylcarbamoyl-4-methyl-4-aza-5 alpha- androstan-3-one (4-MA), an NADPH
      5 alpha-reductase inhibitor, and ketoconazole, a cytochrome P-450 inhibitor, upon
      oxidative metabolism was evaluated. 4-MA caused an increase in detectable
      oxidative products only with microsomes isolated from rat. An increase in 2 alpha
      and 16 alpha-hydroxylation was observed in male rat, and an increase in the
      formation rate of nine products was observed in female rat. delta 6-Progesterone,
      6 beta-, 15 alpha-, 16 alpha-, and 21-hydroxyprogesterone (6 beta-, 15 alpha-, 16
      alpha-, and 21-OHP) were common products in both sexes of all species studied.
      Differences were observed in the formation rate of 2 alpha-, 2 beta-, 6 alpha-, 7
      alpha-, and 17 alpha-OHPs. At the 2-carbon, microsomes isolated from both sexes
      of primates hydroxylated progesterone exclusively at the 2 beta-position.
      Microsomes from both dog sexes and female rat formed 2 alpha- and 2 beta-OHP,
      while microsomes isolated from male rat formed exclusively 2 alpha-OHP. 7 alpha
      Hydroxylation was detected exclusively in rat, and 6 alpha-hydroxylation was
      detected in both dog and rat. 17 alpha-Hydroxylase activity in primates was
      detected only in microsomes from male human. IC50 values associated with
      ketoconazole inhibition of progesterone metabolism differed among
      species.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1981530
TI  - Metabolism of citral, an alpha,beta-unsaturated aldehyde, in male F344 rats.
AB  - Citral is a naturally occurring aliphatic aldehyde of the terpene series and is
      an isomeric mixture of geranial and neral. It is the main component
      (approximately 80%) of lemongrass oil, which is found in all citrus fruits and
      used extensively in the food, cosmetic, and detergent industries. In this study,
      urinary metabolites of citral in male F344 rats were characterized and identified
      by comparison with synthetic standards of known stereochemistry. Stereospecific
      oxidation of citral at the C-8 methyl was investigated, as was the hydrolytic
      sensitivity of biliary and urinary metabolites. For metabolite identification,
      urine was collected over dry ice for 24 hr after a single po 500 mg/kg dose of
      [14C]citral. Elimination in urine was rapid, with approximately 50% of the dose
      excreted within 24 hr. The urine was fractionated by reverse-phase HPLC,
      monitoring both radioactivity and UV. Synthetic standards were prepared; a
      comparison of their spectra with the isolated metabolites was used for
      identification. Citral was rapidly metabolized and excreted as metabolites,
      including several acids and a biliary glucuronide. Seven urinary metabolites were
      isolated and identified: 3-hydroxy-3,7-dimethyl-6-octenedioic acid; 3,8-dihydroxy
      3,7-dimethyl-6-octenoic acid; 3,9-dihydroxy-3,7-dimethyl-6-octenoic acid; E- and
      Z-3,7-dimethyl-2,6-octadienedioic acid; 3,7-dimethyl-6-octenedioic acid; and E
      3,7-dimethyl-2,6-octadienoic acid. Although citral is an alpha,beta-unsaturated
      aldehyde and has the potential of being reactive, the urinary metabolites of
      citral appear to arise from metabolic pathways other than nucleophilic addition
      to the double bond.

PMID- 1981531
TI  - Metabolism of diphenyl sulfoxide in perfused guinea pig liver. Involvement of
      aldehyde oxidase as a sulfoxide reductase.
AB  - To evaluate the metabolic capacity of intact guinea pig liver under normoxic and
      hypoxic conditions, oxidative and reductive metabolism of diphenyl sulfoxide
      (DPSO) was studied by the nonrecirculating perfusion method in situ. DPSO was
      exclusively converted into diphenyl sulfone (DPSO2), an oxidative metabolite,
      under normoxia. When diphenyl sulfide (DPS) was infused, DPSO was eliminated as a
      predominant metabolite. Judging from the susceptibility toward selective
      inhibitors of cytochrome P-450, both oxidative steps appear to be catalyzed by
      cytochrome P-450-dependent monooxygenase rather than flavin adenine dinucleotide
      containing monooxygenase. Under hypoxic conditions, however, DPSO2 formation was
      decreased in parallel with reduced oxygen concentration in the influent
      perfusate, whereas only a trace amount of DPS, a reductive metabolite, was
      detected. On the other hand, coinfusion of an electron donor for aldehyde oxidase
      such as 2-hydroxypyrimidine and benzaldehyde, but not xanthine, markedly
      stimulated the formation of DPS during hypoxia. These results indicate that the
      oxidative pathway catalyzed by cytochrome P-450-dependent monooxygenase is
      predominant in DPSO metabolism under normoxic conditions, whereas only under
      hypoxia does the reductive pathway become the major one if an electron donor for
      aldehyde oxidase exists in intact guinea pig liver.

PMID- 1981532
TI  - Life span profiles of glutathione and acetaminophen detoxification.
AB  - Our previous finding of a glutathione (GSH) deficiency in aging or senescent mice
      suggested that a concomitant decrease in detoxification capacity also may occur.
      To test this, mice at different biological stages of the life span (growth,
      maturity, aging or senescence) were injected with various doses of acetaminophen
      (APAP), and GSH depletion and recovery rates were determined. At intervals for 24
      hr, samples of blood and other tissues were obtained, processed, and analyzed for
      reduced GSH, glutathione disulfide (GSSG), cysteine, and cystine using HPLC with
      dual electrochemical detection. In the uninjected controls, the GSH concentration
      decreased about 30% in all tissues of the aging mouse, but the GSSG cysteine, and
      cystine levels were unchanged during the life span. APAP administration depleted
      liver and lung GSH contents in a dose- and time-dependent manner. Four hr after
      APAP administration, hepatic GSH levels of all ages had decreased 70-80%. After
      24 hr, the GSH levels of the young, growing (3-6 months), and mature (12 months)
      mice recovered to 94 and 66%, respectively, of the controls. In contrast, the
      level in aging (31 months) mice rose only 41%, a lower recovery that was
      correlated with their decreased GSH content. The lungs of old mice also were GSH
      deficient but differed from liver, for there was less GSH depletion by APAP and
      no decrease in GSH recovery. Thus, these findings demonstrate clearly the
      occurrence of decreased detoxification capacity in the GSH-deficient, aging
      mouse.

PMID- 1981533
TI  - Metabolism of the anticonvulsant agent zonisamide in the rat.
AB  - The metabolism of zonisamide [3-(sulfamoylmethyl)-1,2-benzisoxazole], a new
      anticonvulsant, has been studied. In rats dosed with [14C]zonisamide (100 mg/kg,
      ip) 86.5% of the radioactive dose was excreted in the urine over 72 hr. The
      remainder of the radioactive dose (13.5%) was excreted in the feces over the same
      time period. Unchanged drug and eight metabolites were isolated from the urine,
      and the structures of five metabolites were assigned by physicochemical methods.
      metabolism of zonisamide primarily involves reductive and conjugative mechanisms,
      with oxidation of this compound being of minor metabolic significance. The
      percentage of urinary radioactivity accounted for by unmetabolized zonisamide and
      metabolites is as follows: unmetabolized zonisamide (metabolite 9), 32.8%;
      metabolite 8 [N-acetyl-3-(sulfamoylmethyl)-1,2-benzisoxazole], 7.7%; unidentified
      metabolite 7, 2.4%; metabolite 6 (zonisamide glucuronide), 7.6%; metabolite 5 [3
      (carboxy)-1,2-benzisoxazole], 5.4%; unidentified metabolite 4, 13.1%; metabolite
      3 [2-(sulfamoylacetyl)-phenol glucuronide], 12.6%; unidentified metabolite 2,
      3.8%; and metabolite 1 (2-[1-(amino)sulfamoylethyl]phenol sulfate), 2.3%. A total
      of 87.7% of the 0-24 hr urinary radioactivity was accounted for by unchanged
      zonisamide and metabolites.

PMID- 1981534
TI  - Taxol metabolism. Isolation and identification of three major metabolites of
      taxol in rat bile.
AB  - The elimination of nonradioactive taxol in bile and urine was investigated in the
      rat after administration via the caudal vein (10 mg/kg). As in humans, no
      metabolites of taxol were detected by HPLC in rat urine, and only 10% of the
      injected taxol was recovered in urine over a 24-hr period. In contrast, 11.5% and
      29% of the injected taxol was recovered in rat bile as unchanged taxol and
      metabolites, respectively. Among the nine taxol metabolites detected by HPLC, the
      side chain at C13, which is required for pharmacological activity, had been
      removed in only one minor metabolite, baccatin III. The chemical structures of
      the two major hydroxylated metabolites were determined by mass spectrometry (fast
      atom bombardment and desorption chemical ionization) and 1H-NMR spectroscopy. One
      was a taxol derivative hydroxylated on the phenyl group at C3' of the side chain
      at C13, while the other corresponded to a taxol derivative hydroxylated in the m
      position on the benzoate of the side chain at C2. Although these two major taxol
      metabolites were as active as taxol in preventing cold microtubule disassembly,
      they were, respectively, 9 and 39 times less cytotoxic as taxol on in vitro L1210
      leukemia growth. These results show for the first time that there is a
      significant hepatic metabolism of taxol.

PMID- 1981535
TI  - Physiological pharmacokinetics of a new muscle-relaxant, inaperisone, combined
      with its pharmacological effect on blood flow rate.
AB  - This study was designed to develop a physiologically-based
      pharmacokinetic/pharmacodynamic model for drugs whose pharmacokinetics are
      influenced by their dose-dependent pharmacological effects. Since blood flow rate
      is one of the important factors that determine the distribution and elimination
      processes of drugs, we used inaperisone [IPS, (+/-)-4'-ethyl-2-methyl-3-(1
      pyrrolidinyl)-propiophenone hydrochloride], a novel centrally acting muscle
      relaxant that has been found by us to significantly alter muscle and fat blood
      flow rates in a dose-dependent manner, as a model compound. With regard to the
      changes in muscle blood flow rate exhibited by IPS, the brain was shown to be the
      major site of action based on changes in the observed blood flow rates,
      determined by the 51Cr-labeled microsphere method, in rats injected iv and
      intracerebroventricularly with various doses of IPS. Consequently, the blood flow
      rates in the muscle and fat were well correlated with the concentration of IPS in
      the brain using Hill's equation. Moreover, hepatic and renal intrinsic clearances
      of IPS at steady-state were determined by the constant iv infusion method. The
      saturation of in vivo hepatic and renal metabolisms of IPS was found at venous
      plasma concentrations higher than 1 microgram/ml. Taken all together, we
      developed a physiologically-based pharmacokinetic model of IPS combined with its
      pharmacological effect in rats, which could simulate the concentration-dependent
      changes in blood flow rates based on the drug concentrations at the site of
      action.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1981536
TI  - Metabolism of hexafluoropropene. Evidence for bioactivation by glutathione
      conjugate formation in the kidney.
AB  - We investigated the metabolism of hexafluoropropene, a nephrotoxic fluoroalkene,
      in rat liver and kidney subcellular fractions and in rats in vivo. Incubation of
      hexafluoropropene (1 mM) with microsomes and cytosol in the presence of
      glutathione (GSH) yielded S-(1,2,3,3,3-pentafluoropropenyl)glutathione (PPFG) and
      S-(1,1,2,3,3,3-hexafluoropropyl)glutathione (HFPG) as identified by thermospray
      mass spectrometry and 1H-NMR. In liver microsomes, PFPG formation was predominant
      (240 nmol/min/mg protein) over HFPG (36 nmol/min/mg), whereas in cytosol, HFPG
      was the only hexafluoropropene metabolite (136 nmol/min/mg) detectable. In kidney
      microsomes, GSH-conjugate formation could not be detected; in kidney cytosol,
      HFPG was exclusively formed (46 nmol/min/mg). Hexafluoropropene inhalation (800
      ppm for 1 hr) in rats fitted with a biliary cannula resulted in the biliary
      elimination of PFPG without detectable formation of HFPG; the exclusively formed
      urinary metabolite, identified by GC/MS, was N-acetyl-S-(1,1,2,3,3,3
      hexafluoropropy)-L-cysteine. The results show that hexafluoropropene is
      metabolized to two different GSH-conjugates in rat liver and kidney. The data
      also suggest that hexafluoropropene metabolites formed in the liver and
      eliminated with bile are not translocated to the kidney and that intrarenal
      bioactivation by GSH-conjugation may be responsible for hexafluoropropene-induced
      nephrotoxicity.

PMID- 1981537
TI  - In vivo metabolites of S-(2-benzothiazolyl)-L-cysteine as markers of in vivo
      cysteine conjugate beta-lyase and thiol glucuronosyl transferase activities.
AB  - Cysteine conjugate beta-lyases (beta-lyase), enzymes that are present in
      mammalian liver, kidneys, and intestinal microflora, were exploited recently for
      site-selective delivery of 6-mercaptopurine to the kidneys. In this study, in
      vivo beta-lyase activity was assessed using S-(2-benzothiazolyl)-L-cysteine
      (BTC). 2-Mercaptobenzothiazole and 2-mercaptobenzothiazole S-glucuronic acid were
      major metabolites of BTC in rat liver, kidney, plasma, and urine. Total
      metabolite concentrations in liver, kidney, or plasma at 30 min were similar and
      were higher than that detected at 3 hr; metabolites were mostly in the
      glucuronide form. The portions of metabolites excreted in urine at 8 and 24 hr
      were nearly 93 and 99% of that excreted at 40 hr, respectively. Pretreatment of
      rats with aminooxyacetic acid did not alter kidney, liver, plasma, or urinary
      metabolite concentrations. The portion of the BTC dose excreted as metabolites at
      24 hr was independent of the BTC dose (100-400 mumol/kg), age (5-12 weeks), or
      sex of the rats. The rates of in vitro BTC metabolism by guinea pig hepatic and
      renal beta-lyases were slower than those of rats, but the portion of the BTC dose
      recovered as metabolites in guinea pig urine at 24 hr was nearly 60%, which was
      nearly 2-fold higher than that recovered in urine of rats, mice, or hamsters. The
      amounts of total metabolites excreted into urine by mice or hamsters were
      similar, but the portion of metabolites that was in the glucuronide form in
      hamster urine was higher than that in mouse urine.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1981538
TI  - Metabolism and disposition of the dopamine agonist 2-(N-propyl-N-2
      thienylethylamino)-5-hydroxytetralin in conscious monkeys after subsequent i.v.
      oral, and ocular administration.
AB  - The metabolism of 2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin (N-0437)
      was investigated in conscious monkeys after subsequent i.v., oral, and ocular
      administration. The administration of the drug caused some physiological effects,
      such as bradycardia and sedation of the monkeys. During a collection period of
      120 hr, on average 83% was recovered after iv administration and 90% after p.o.
      dosing. After i.v. administration, 44% was excreted in the bile, as compared to
      38% in the urine and about 1% in the feces. After oral administration, bile is
      the major excretion route, accounting for about 60% of the dose, as compared to
      25% in the urine and about 5% in the feces. After ocular administration, on
      average 62% was recovered after 7 hr, excreted in bile and urine in about equal
      amounts. All percentages given above reflect the total amount of radioactivity
      recovered, thus comprising the unchanged drug plus various metabolites. After all
      three dosing routes, N-0437 was metabolized almost completely prior to
      elimination. Direct glucuronidation of the phenolic group proved to be the major
      metabolic pathway of N-0437, comprising about 44% of the dose after i.v. and
      ocular administration and 72% after oral dosing. Hydroxylation of N-0437 at the
      position ortho to the phenolic group present yielded a catechol intermediate,
      which was excreted as a glucuronide and accounted for about 10% of the dose. In
      the monkey, a clear regioselective preference towards glucuronidation at the 6
      position was observed. Besides the glucuronide, the sulfoconjugate of N-0437 was
      a major metabolite after i.v. and ocular administration, accounting for about 15%
      of the dose.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1981539
TI  - Metabolism and covalent binding of [14C]toluene by human and rat liver microsomal
      fractions and liver slices.
AB  - The in vitro metabolism of [14C]toluene by liver microsomes and liver slices from
      male Fischer F344 rats and human subjects has been compared. Rat liver microsomes
      produced only benzyl alcohol from toluene. Liver microsomes from human subjects
      metabolized toluene to benzyl alcohol, benzaldehyde, and benzoic acid. Liver
      microsomes from one human donor also produced p-cresol and o-cresol. The overall
      rate of toluene metabolism by human liver microsomes was 9-fold greater than by
      rat liver microsomes. Human liver microsomal metabolism of benzyl alcohol to
      benzaldehyde required NADPH and was inhibited by carbon monoxide and high pH (pH
      10). but was not inhibited by ADP-ribose or sodium azide. These results suggest
      that cytochrome P-450, rather than alcohol dehydrogenase, was responsible for the
      metabolism of benzyl alcohol to benzaldehyde. Human and rat liver slices
      metabolized toluene to hippuric acid and benzoic acid. The overall rate of
      toluene metabolism by human liver slices was 1.3-fold greater than by rat liver
      slices. Cresols and cresol conjugates were not detected in human or rat liver
      slice incubations. Covalent binding of [14C]toluene to human liver microsomes and
      slices was 21-fold and 4-fold greater than to the comparable rat liver
      preparations. Covalent binding did not occur in the absence of NADPH, was
      significantly decreased by coincubation with cysteine, glutathione, or superoxide
      dismutase, and was unaffected by coincubation with lysine. Protease and
      ribonuclease digestion decreased the amount of toluene covalently bound to human
      liver microsomes by 78% and 27% respectively. Acid washing of human liver
      microsomes had no effect on covalent binding.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1981540
TI  - Diflunisal disposition. Role of gastric absorption in the development of mucosal
      damage and anti-inflammatory potency in rodents.
AB  - Aspirin shows a high incidence of gastric side effects. These are thought to
      result from both systemic and local effects during drug absorption. In contrast,
      a lipophilic derivative of salicylic acid, diflunisal, causes significantly fewer
      adverse gastric effects. This is thought to be due to a lack of gastric
      absorption. To test this hypothesis, three types of experiments were performed
      with diflunisal: 1. Transgastric permeation was quantified under different pH
      conditions, using an isolated mouse stomach model. 2. Ulcerogenic potencies of
      buffered and unbuffered drug solutions were determined in rats. 3. The time
      course of its anti-inflammatory effect and the serum concentrations of
      diflunisal, given alone and with neutralizing buffer, were measured in rats with
      carrageenan-induced paw edema. Corresponding to the low gastric ulcerogenicity,
      absorption of diflunisal in the isolated stomach preparations was very small.
      However, absorption was pH-dependent and ranged between 0.69 and 8.73% with a
      maximum at pH 4.5. Gastric lesions were found to be more evident 24 hr after drug
      administration than after 5 hr. Comparing buffered vs. unbuffered diflunisal
      preparations, no difference in ulcerogenicity was detectable. However, using a
      buffered preparation, the anti-inflammatory effect of diflunisal was enhanced
      significantly (p less than 0.01), and elevated serum concentrations were found (p
      less than 0.05). The results show that raising the solubility of diflunisal does
      not influence gastric absorption or gastric toxicity considerably. However, its
      serum concentrations and systemic anti-inflammatory effects were significantly
      enhanced.

PMID- 1981542
TI  - The metabolism of etintidine in rat, dog, and human.
AB  - The metabolic fate of etintidine, a new H2-receptor antagonist, was studied in
      the rat, dog, and human. Following oral or iv administration of [14C]etintidine
      HCl to rats, 63-72% of the dose was eliminated in urine and 15-28% in feces over
      3 days. In dogs, 52-70% of the administered dose was excreted in urine and 14-18%
      in feces over 5 days. In the urine of both species, the major portion (generally
      greater than 70%) of the radioactivity was associated with parent drug and its
      sulfoxide metabolite. In rats, a distinct sex-related difference in metabolism
      was observed following oral administration of 20 mg/kg doses, with males
      excreting nearly twice the amount of the sulfoxide relative to females. A
      significant sex-related difference in metabolism was not observed in dogs
      following oral administration of a comparable dose, nor was it observed in either
      species following iv drug administration. After oral administration of
      [14C]etintidine HCl to human volunteers, about 86% of the dose was recovered in
      urine and 13% in the feces over a 7-day period. In humans, the major urinary
      metabolite was the N'-glucuronide conjugate. Thus, sulfoxidation does not appear
      to be the major urinary metabolic pathway of the drug in humans, as it is in
      animals. The metabolic fate of etintidine and cimetidine, another H2-receptor
      antagonist, are compared in three species.

PMID- 1981541
TI  - Cytochrome P-450 isozymes in metabolic activation of delta 9-tetrahydrocannabinol
      by rat liver microsomes.
AB  - delta 9-Tetrahydrocannabinol (THC) was incubated with a reconstituted system
      consisting of dilauroylphosphatidylcholine, NADPH-cytochrome c reductase,
      cytochrome b5, and cytochrome P-450 (P-450) isozyme UT-2, UT-4, or UT-5, which
      was purified from liver microsomes of adult male rats. It was biotransformed by
      UT-2 to 11-OH-delta 9-THC and 3'-OH-delta 9-THC, and by UT-4 to 8 beta-OH-delta 9
      THC and 11-OH-delta 9-THC. UT-5, however, showed only a little activity for 11-OH
      delta 9-THC formation. Activity of the isozyme UT-2 for 11-OH-delta 9-THC
      formation from delta 9-THC was calculated to be 4.07 nmol/min/nmol P-450 while
      those of UT-2 for the formations of 16 alpha-OH-testosterone (16 alpha-OH-T), 2
      alpha-OH-T, and androstenedione from testosterone were 14.7, 6.6, and 2.2
      nmol/min/nmol P-450, respectively. Anti-P-450 UT-2 IgG fraction obtained from
      rabbit serum dose-dependently suppressed formations of 16 alpha-OH-T, 2 alpha-OH
      T, and androstenedione from testosterone with liver microsomes of adult male
      rats. The antibody, in the amount that inhibited above 90% of 16 alpha-OH-T and 2
      alpha-OH-T formations from testosterone, also reduced 80% of the microsomal
      formations of 11-OH-delta 9-THC and 3'-OH-delta 9-THC from delta 9-THC, as
      compared with control experiments using preimmune IgG fraction.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1981543
TI  - Ciprofloxacin does not impair the elimination of diazepam in humans.
AB  - The pharmacokinetics of a single iv dose of 10 mg diazepam and the renal
      excretion of its metabolites resulting from N-demethylation and C-3-hydroxylation
      were investigated in 10 healthy volunteers when diazepam was administered alone
      and on day 3 of administration of the fluoroquinolone ciprofloxacin (500 mg twice
      per day). No significant changes in the diazepam half-life, its volume of
      distribution, the total body clearance, or the renal clearance were observed. In
      addition, the renal excretion of the metabolites desmethyldiazepam, 3
      hydroxydiazepam (temazepam), and 3-hydroxydesmethyldiazepam (oxazepam) were not
      altered by ciprofloxacin co-medication. These data demonstrate that in a 500 mg
      twice per day oral dosage, ciprofloxacin does not influence the metabolic
      clearance of diazepam in young healthy volunteers.

PMID- 1981544
TI  - Identification of N-acetyl-S-(2,5-dihydroxyphenyl)-L-cysteine as a urinary
      metabolite of benzene, phenol, and hydroquinone.
AB  - The metabolite 2-(S-glutathionyl)hydroquinone is formed when a microsomal
      incubation mixture containing either benzene or phenol is supplemented with
      glutathione. This metabolite is derived from the conjugation of benzoquinone, an
      oxidation product of hydroquinone. However, neither the glutathione conjugate or
      its mercapturate, N-acetyl-S-(2,5-dihydroxyphenyl)-L-cysteine, have been
      identified as metabolites resulting from in vivo metabolism of benzene, phenol,
      or hydroquinone. To determine if a hydroxylated mercapturate is produced in vivo,
      we treated male Sprague-Dawley rats with either benzene (600 mg/kg), phenol (75
      mg/kg), or hydroquinone (75 mg/kg) and collected the urine for 24 hr. HPLC
      coupled with electrochemical detection confirmed the presence of a metabolite
      that was chromatographically and electrochemically identical to N-acetyl-S-(2,5
      dihydroxyphenyl)-L-cysteine. The metabolite was isolated from the urine samples
      and treated with diazomethane to form the N-acetyl-S-(2,5-dimethoxyphenyl)-L
      cysteine methyl ester derivative. The mass spectra obtained from these samples
      were identical to that of an authentic sample of the derivative. The results of
      these experiments indicate that benzene, phenol, and hydroquinone are metabolized
      in vivo to benzoquinone and excreted as the mercapturate, N-acetyl-S-(2,5
      dihydroxyphenyl)-L-cysteine.

PMID- 1981546
TI  - Disposition in humans of racemic picenadol, an opioid analgesic.
AB  - Racemic picenadol is being tested clinically as an analgesic. The (+)-enantiomer
      of picenadol is an opioid agonist and the (-)-enantiomer is a weak
      agonist/antagonist. The disposition of racemic [14C] picenadol was studied in
      healthy men after a single dose was administered im (N = 3) and orally (N = 5).
      After the dose, virtually none of the radioactivity that appeared in blood was
      associated with the red cells. In plasma, approximately 4% of the radioactivity
      was attributable to the parent drug, the remainder being picenadol glucuronide
      (approximately 35%) and other metabolites. The t1/2 for total radioactivity was 6
      hr, that for the unchanged drug was 3.5 hr. Picenadol was present in plasma
      almost exclusively as the (+)-enantiomer. However, after incubation with
      glucuronidase and sulfatase, plasma contained 2 to 4 times more (-)- than (+)
      picenadol, indicating that more conjugated (-)-picenadol than conjugated (+)
      picenadol was in the plasma. After im and oral administration of [14C]picenadol,
      plasma levels of radioactivity were generally 10 and 70 times higher than those
      in saliva, respectively. More than 90% of the administered radioactivity was
      excreted in the urine, mostly as picendol glucuronide, and lesser amounts of
      picenadol sulfate and N-desmethylpicenadol sulfate. Only about 1% of the
      administered dose of picenadol appeared unchanged in urine. The disposition of
      racemic picenadol in humans was stereoselective, the (-)-picenadol apparently
      being metabolized preferentially over the (+)-enantiomer. This finding was of
      particular interest in view of the dissimilar pharmacologic activities of the
      enantiomers.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1981545
TI  - Effects of sodium salicylate on elimination kinetics of indomethacin and bile
      production in dogs.
AB  - We investigated the effects of sodium salicylate on the elimination kinetics of
      indomethacin in bile duct-cannulated beagles. Indomethacin and metabolites were
      quantified by HPLC in plasma, bile, and urine. Indomethacin was administered as
      iv bolus injection and iv infusion to yield a steady-state plasma concentration
      of approximately 1 microgram/ml. Following sodium salicylate, given either iv (25
      mg/kg) or via duodenal fistula (50 mg/kg), the indomethacin plasma level dropped
      instantaneously by 60-70%. Concomitantly, total systemic clearance from the
      plasma and biliary clearance were increased significantly. In addition, a reduced
      plasma protein binding of indomethacin and a significant increase in the volume
      of distribution were observed. The amount of indomethacin, excreted as free and
      conjugated drug in bile, was significantly increased temporarily by sodium
      salicylate. The total amount eliminated in bile (approximately 70% of the dose),
      however, was not changed by sodium salicylate co-administration. The bile flow
      was significantly enhanced for at least 4 hr. Both phase 1 metabolism and renal
      excretion of indomethacin remained practically unaffected by sodium salicylate
      treatment.

PMID- 1981548
TI  - Metabolic disposition of trimetrexate, a nonclassical dihydrofolate reductase
      inhibitor, in rat and dog.
AB  - The metabolic disposition of trimetrexate, a nonclassical inhibitor of
      dihydrofolate reductase, was characterized in the rat. After iv administration of
      1.2 mg/kg [14C]trimetrexate (as the glucuronate), recovery of total radioactivity
      in urine and feces through 144 hr was greater than 96% of dose. Trimetrexate was
      extensively metabolized, with only 13% of the dose excreted unchanged in urine
      and bile. Profiling of biliary and urinary radioactivity showed three components
      and unchanged drug accounted for the majority of excreted radioactivity (75% of
      dose). Tandem mass spectral analysis of one urinary component suggested
      trimetrexate had undergone N-dealkylation and oxidation to 2,4-diamino-5-methyl-6
      quinazolinecarboxylic acid. Structural assignment for this metabolite was
      confirmed by comparison to authentic reference material. Mass spectral analysis
      of a second component gave a quasimolecular ion (MH)+ at m/z 532 with a key
      fragment ion at m/z 356 (MH-176)+, characteristic of a glucuronide conjugate. The
      proton NMR spectrum of this component was consistent with expectations for a
      glucuronide conjugate of 4'-O-desmethyl trimetrexate. Possible formation of a
      sulfate conjugate was explored by co-administration of unlabeled trimetrexate
      with [35S]sulfate to rats. A 35S-labeled component was excreted in urine, which
      co-eluted with the third major urinary 14C-labeled component observed in the
      first experiment. Mass spectrum of this component was consistent with the
      structure of trimetrexate-4'-O-desmethyl sulfate. In dogs, the disposition of
      trimetrexate was examined using stable isotope-labeled material. The dose was 10
      mg/kg administered iv as a 1:1 mixture of 13C2, 15N-labeled and unlabeled
      trimetrexate glucuronate.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1981547
TI  - Isotope effect studies on the mechanism of the cytochrome P-450IIA1-catalyzed
      formation of delta 6-testosterone from testosterone.
AB  - Testosterone metabolism by cytochrome P-450IIA1 results in four metabolites: 6
      alpha-hydroxytestosterone; 7 alpha-hydroxytestosterone; 17 beta-hydroxy-4,6
      androstadiene-3-one (delta 6-T); and 17 beta-hydroxy-4,6-androstadiene-3-one-6,7
      oxide. The epoxide is formed upon further oxidation of delta 6-T, and its
      formation is in competition with the dissociation of delta 6-T from the active
      site. The analysis of the KM and Vmax values, as well as the product ratios for
      testosterone and three selectively deuterated analogs, strongly suggest that
      delta 6-testosterone formation occurs primarily by initial hydrogen atom
      abstraction at the 6 alpha-position followed by abstraction of the 7 alpha
      hydrogen atom.

PMID- 1981549
TI  - Pharmacokinetics of propafenone enantiomers in rats.
AB  - Pharmacokinetics of propafenone (PPF) enantiomers were investigated in adult male
      Sprague-Dawley rats after iv, po, and ip administration of a single 10 mg/kg dose
      of the racemate. After all routes of administration, the AUC for the (-)
      enantiomer was significantly higher than that of its antipode: the mean +/- SD
      values of (-):(+) AUC ratio were 1.99 +/- 0.228, 2.52 +/- 0.525, and 3.54 +/-
      1.12 for the iv, ip, and po data, respectively. The respective absolute
      bioavailabilities of the (-)- and (+)-enantiomers were 0.422 and 0.254 after po
      administration and 0.493 and 0.402 after ip administration, indicating
      stereoselectivity in the first-pass metabolism of the drug. Only negligible
      amounts of the enantiomers were excreted unchanged into the urine of rats,
      suggesting that elimination of PPF in rats, as in humans, is almost entirely
      dependent on its metabolism. Compared with the iv and ip data, serum
      concentrations of the enantiomers after po administration remained above the
      assay sensitivity for a longer period of time. This was due to the presence of
      multiple peaks in the serum concentration-time courses of the enantiomers after
      po administration. In an exploratory experiment, it was shown that co
      administration of quinidine sulfate drastically increases serum concentrations of
      both PPF enantiomers. The results of our study indicate that, in rats,
      pharmacokinetics of PPF are stereoselective and that the route of administration
      affects the degree of this stereoselectivity.

PMID- 1981550
TI  - Oxidative defluorination of 1,1,1,2-tetrafluoroethane by rat liver microsomes.
AB  - 1,1,1,2-Tetrafluoroethane (R-134a) is a non-ozone-depleting alternative to
      dichlorodifluoromethane for use as an air-conditioning refrigerant and as a
      propellant in anti-asthmatic and other pharmaceutical preparations. Hepatic
      microsomes, supplemented with NADPH, catalyzed the release of F- from R-134a;
      metabolite production was positively correlated with both duration of incubation
      and gas phase [R-134a]. Defluorination of R-134a was inhibited by CO, lack of
      NADPH, or heat denaturation of microsomes. Release of F- from R- 134a
      biotransformation as shown by the near-total lack of dehalogenation during
      anaerobic incubations. R-134a did not produce a difference spectrum (360 to 500
      nm) with either oxidized or dithionite-reduced microsomes. Microsomes from
      phenobarbital- or Aroclor 1254-treated rats produced greater amounts of F- per mg
      protein from high concentrations of R-134a than did microsomes from untreated
      rats, but when normalized for microsomal cytochrome P-450 content both
      phenobarbital and Aroclor treatment decreased the specific activity (nmol F-/nmol
      cytochrome P-450) of R-134a metabolism. Furthermore, while defluorination of R
      134a by microsomes from livers of untreated rats was substrate-saturable (Vmax,
      11 nmol of F-/nmol cytochrome P-450/15 min; KM, 8% R-134a), R-134a dehalogenation
      by microsomes from Aroclor-treated rats was nonsaturable with [R-134a] as high as
      69%. Microsomes from phenobarbital-treated rats retained the saturable, low KM
      activity, but also exhibited the apparently nonsaturable kinetic component when
      [R-134a] was greater than 24%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1981552
TI  - Similar myocardial effects of aging and hypertension.
AB  - Aging has sometimes been referred to as 'blunted hypertension', and hypertension
      as 'accelerated aging'. Systolic arterial pressure increases with aging; the
      increase encompasses both the clinically normal and hypertensive ranges of
      pressure and is due in part to arterial stiffening. Cardiac changes that occur
      with aging in otherwise healthy individuals can occur at a younger age in
      clinically hypertensive individuals and can be produced in young animals by
      experimental hypertension. Such cardiac adaptations in hypertension and aging
      include left ventricular hypertrophy and prolonged Ca2+ activation of contractile
      proteins, leading to a prolonged force-bearing capacity. This is mediated by a
      prolongation of the cytosolic Ca2+ transient, due to a reduced rate of Ca2+
      sequestration by the sarcoplasmic reticulum. The action potential is also
      prolonged. The resultant delayed contractile relaxation, in part, leads to a
      slower velocity of early diastolic left ventricular filling; however, this is
      offset by enhanced atrial filling. Cardiac muscle of the aging and hypertensive
      heart are also less sensitive to beta-adrenergic stimulation. These myocardial
      adaptations with aging and hypertension, in part, are controlled from within the
      genome and permit a relatively normal heart volume and ejection fraction in the
      presence of chronically elevated afterload.

PMID- 1981551
TI  - The use of pig hepatocytes to study the biotransformation of beta-nortestosterone
      by pigs. Identification of glucuronidated 15 alpha-hydroxy-norandrostenedione as
      an important in vitro and in vivo metabolite.
AB  - Porcine hepatocytes were used to examine the biotransformation of beta
      nortestosterone (NOR). Initially, the major metabolite of NOR was
      norandrostenedione (NA), which upon prolonged incubation was further transformed,
      primarily to the glucuronide of 15 alpha-hydroxy-norandrostenedione (15 alpha OH
      NA). No differences were observed in this pattern between hepatocytes isolated
      from livers of sows or castrated male pigs. With increasing culture age, the rate
      of formation of NA did not change, contrary to a decrease in its further
      oxidation and glucuronidation. 15 alpha-OH-NA, primarily as its glucuronide, was
      identified in the urine of pigs injected with NOR. In addition, NA and the
      glucuronide of the parent compound were present in much smaller amounts.

PMID- 1981553
TI  - In vivo interaction of cabergoline with rat brain dopamine receptors labelled
      with [3H]N-n-propylnorapomorphine.
AB  - Cabergoline is a potent dopaminergic agent that interacts with agonists and
      antagonists of dopamine receptors in vitro. We studied the binding of [3H]N-n
      propylnorapomorphine ([3H]NPA) to dopamine receptors after i.v. and oral
      administration of cabergoline to determine whether cabergoline crosses the blood
      brain barrier; bromocriptine was used as a reference drug. Cabergoline and/or its
      active metabolite(s) did cross the blood-brain barrier and reach dopamine
      receptors. Comparative time-course analysis of the regional inhibition of [3H]NPA
      binding showed that cabergoline was more potent than bromocriptine in inhibiting
      [3H]NPA binding and that it occupied the receptor for longer. These effects were
      observed in all areas of the rat brain studied (striatum, olfactory tubercles,
      adeno- and neurohypophysis, thalamus and hypothalamus). Further studies in the
      striatum and adenohypophysis showed that cabergoline receptor occupancy was dose
      dependent and still detectable 72 h after i.v. administration of the drug. While
      cabergoline was more potent in the striatum than in the adenohypophysis when
      administered i.v., the reverse was observed after its oral administration.
      Cabergoline was equally potent in the adenohypophysis after oral and i.v.
      administration, as determined 1 and 8 h later.

PMID- 1981554
TI  - Inhibition of sympathetic neurotransmitter release by modulators of cyclic GMP in
      canine vascular smooth muscle.
AB  - The contractile response to neurally released norepinephrine (NE) from
      sympathetic nerve endings innervating vascular smooth muscle are inhibited by
      substances which raise either cyclic AMP and cyclic GMP concentrations in smooth
      muscle. However, cyclic AMP is believed to facilitate NE release from sympathetic
      nerves whereas the role of cyclic GMP in this process is undefined. We examined
      the effects of presumed modulation of the intraneuronal concentration of cyclic
      AMP and cyclic GMP on sympathetic neurotransmission to isolated canine mesenteric
      artery by measurement of the efflux of [2-14C]NE during transmural nerve
      stimulation (calcium dependent release of NE) and administration of tyramine
      (calcium independent release of NE) and measurement of the contractions to
      exogenous NE and tyramine. Stimulation of adenylate cyclase with forskolin,
      prostacyclin and iloprost, a stable prostacyclin analog, and inhibition of Type
      III cyclic AMP phosphodiesterase with neural specific rolipram, 'non-specific
      pelrinone and milrinone and isobutylmethylxanthine did not enhance the efflux of
      [2-14C]NE from sympathetic nerves innervating the blood vessels. Isoproterenol
      enhanced the efflux of [2-14C]NE. The effect was inhibited by propranolol but not
      affected by milrinone, amrinone or rolipram. Activators of guanylate cyclase (SIN
      1a an active metabolic of molsidomine, nitroglycerin and sodium nitroprusside)
      and inhibitors of Type II cyclic GMP phosphodiesterase (M&B-22948 and verofyllin)
      inhibited the efflux of NE released by transmural nerve stimulation but not by
      tyramine. These data support the conclusion that cyclic GMP may be an inhibitory
      modulator of calcium and depolarization dependent NE release from sympathetic
      nerves, whereas neuronal cyclic AMP may not be a primary modulator of
      neurotransmission to vascular smooth muscle.

PMID- 1981555
TI  - Differences in pharmacological profiles of a new generation of benzodiazepine and
      non-benzodiazepine hypnotics.
AB  - The hypnotics, quazepam (a benzodiazepine), brotizolam (a
      thienotriazolodiazepine), zopiclone (a cyclopyrrolone) and zolpidem (an
      imidazopyridine) have a common ability to bind to the benzodiazepine recognition
      site (omega receptor) within the GABAA receptor. For this reason we compared
      their pharmacological profiles in mice. All compounds shared anticonvulsant and
      central depressant effects. However, the sedative activity of zolpidem appeared
      at much lower doses than did the anticonvulsant and myorelaxant effects but the
      opposite was observed with the other hypnotics. In contrast to brotizolam,
      quazepam and zopiclone, zolpidem did not increase food intake in mice placed in a
      novel environment, indicating that this drug lacks disinhibitory activity.
      Moreover the efficacy of zolpidem at the GABAA receptor, as indicated by its
      activity against convulsions induced by the GABA synthesis inhibitor, isoniazid,
      was much greater than that of other hypnotics. These results suggest that the
      hypnoselective properties observed with zolpidem might be related to a high
      selectivity for the omega 1 recognition site of the GABAA receptor coupled with a
      very high intrinsic activity.

PMID- 1981556
TI  - Selective alpha 2-adrenoceptor blockade does not enhance glucose-evoked insulin
      release.
AB  - An investigation has been made of the effects of the selective alpha 2
      adrenoceptor antagonist, idazoxan, on the plasma immunoreactive insulin and
      glucose responses following a glucose stimulus in conscious euglycaemic rats. UK
      14304 (100 micrograms/kg), a selective alpha 2-adrenoceptor agonist, reduced the
      insulin response and potentiated the hyperglycaemia elicited by an intra-arterial
      glucose load (0.25 g/kg), thereby confirming previous findings that alpha 2
      adrenoceptors can influence pancreatic insulin secretion and glycaemia. The
      effects of UK 14304 were totally abolished by idazoxan (1.0 mg/kg), indicating
      that idazoxan, at the dose studied, effectively antagonized alpha 2-adrenoceptor
      mediated responses. However, idazoxan (1.0 mg/kg) by itself did not significantly
      affect the plasma glucose and insulin responses to glucose challenge. The data
      indicate that selective alpha 2-adrenoceptor blockade per se does not potentiate
      glucose-evoked insulin secretion.

PMID- 1981557
TI  - Anxiolytic potential of a microgram dose of chlordiazepoxide in the open-field
      test.
AB  - Diazepam, when administered in very low doses (100 micrograms/kg), can induce a
      specific inhibition of coarse and ambulation activities in the rat, suggesting a
      novel mechanism of action occurring in the microgram dose range. This study fails
      to reproduce the same effects with chlordiazepoxide. On the contrary, greater
      stimulant and anxiolytic effects were measured with the lowest dose tested (0.1
      mg/kg). These results demonstrate that the familiar effects of benzodiazepines
      should not be extrapolated uncritically to lower dose ranges without empirical
      testing.

PMID- 1981558
TI  - Vinpocetin protects against excitotoxic cell death in primary cultures of rat
      cerebral cortex.
AB  - The protective effect of vinpocetin, a drug clinically useful in brain
      hypoxia/ischemia, was examined in vitro on cerebrocortical cultures treated with
      glutamate and related excitotoxins. The extent of cell death was quantified by
      measuring lactic dehydrogenase activity released from damaged cells into the
      culture medium. Vinpocetin partially protected the cortical cells against cell
      death induced by N-methyl-D-aspartate, quisqualate and kainate, indicating that
      the drug exerts a direct protective action on cerebrocortical cells bearing
      excitatory amino acid receptors.

PMID- 1981560
TI  - Stimulation of the T-cell receptors CD3 and CD2 with OKT3 and OKT11 antibodies
      activates a common pertussis toxin-insensitive G-protein.
AB  - The association of G-proteins with the T-cell-specific receptor structures CD3
      and CD2 was investigated. High-affinity GTPase activity in membrane preparations
      of the human leukemic T-cell line Jurkat could be induced by the monoclonal
      antibodies OKT3 (anti-CD3) and OKT11 (anti-CD2). When combining maximally active
      concentrations of OKT3 and OKT11, no additive effect was seen on GTPase activity.
      In mutant Jurkat cells lacking the CD3 complex but with an intact CD2 receptor,
      neither OKT3 nor OKT11 could stimulate GTPase activity. Activation of CD3 and CD2
      by monoclonal antibodies also stimulated phospholipase C activity as measured by
      breakdown of membrane phosphoinositides in wild-type but not in mutant Jurkat
      cells. Neither GTPase nor phospholipase C activation was sensitive to
      pretreatment with doses of pertussis toxin (PTX) that caused ADP ribosylation of
      a sensitive G-protein. Our data show that the CD3 complex and the CD2 receptor
      may activate a common PTX-insensitive G-protein. The CD2 receptor appears to
      stimulate the G-protein by interacting with the CD3 complex. The data are
      compatible with, but do not prove, that this G-protein is involved in the
      activation of phospholipase C by the two receptors.

PMID- 1981559
TI  - Identification and characterization of a high-affinity glutamate-controlled TCP
      binding site in rat brain postsynaptic densities.
AB  - The kinetic and equilibrium binding parameters of the phencyclidine receptor
      ligand [3H]N-[1-(2-thienyl)cyclohexyl]piperidine (TCP) to a postsynaptic density
      (PSD) subcellular fraction from rat brain were investigated. A single site was
      found, which was identified as the high-affinity TCP binding site by competition
      with dibenzocycloalkenimine (MK-801). In contrast, [3H]TCP binds to two sites on
      the plasma membrane fraction used as a precursor for PSD; on both fractions,
      [3H]TCP binding responds to glutamate by an increase of the association rate, the
      dissociation constant and the number of sites being unchanged. In the PSD
      fraction [3H]3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP), an
      antagonist specific for the N-methyl-D-aspartate (NMDA) site, bound to high- and
      low-affinity sites. These results ascertain the presence and identity of synaptic
      NMDA-gated ion channels, which are assumed in the current hypothesis about
      excitotoxicity, long-term potentiation and learning.

PMID- 1981561
TI  - Effects of dopamine, D-1 and D-2 dopaminergic agonists on the excitability of
      hippocampal CA1 pyramidal cells in guinea pig.
AB  - In hippocampal pyramidal cells (HPCs), Dopamine (DA) application (1 microM)
      produced, in 50% of recorded cells, an hyperpolarization of the resting membrane
      potential (r.m.p.) and an increase of the afterhyperpolarization (AHP) amplitude
      and duration in 79% of recorded cells. DA-induced effects on both the r.m.p. and
      AHP were mimicked by bath application of a D-1 selective agonist, SKF 38393 (20
      microM). In addition, we have observed that a D-1 selective antagonist such as
      SCH 23390 (1 microM) abolished the action of both DA and SKF 38393. In contrast,
      the activation of D-2 receptors through LY 171555 (10 microns) produced, in 50%
      of cells, a depolarization of the r.m.p. and a depression of the AHP in 67% of
      recorded cells. These results suggest that the effects observed in hippocampal
      pyramidal neurons after DA application of micromolar concentration are mediated
      by D-1 subtype of receptors.

PMID- 1981562
TI  - Swallowing responses induced by microinjection of glutamate and glutamate
      agonists into the nucleus tractus solitarius of ketamine-anesthetized rats.
AB  - Swallowing is a patterned motor activity generated by neurons located within the
      nucleus tractus solitarius (NTS). An excitatory amino acid (EAA)
      neurotransmitter, such as glutamate (GLU), is suspected of being involved in the
      initiation of swallowing by NTS neuronal components. However, swallowing can
      still be elicited in animals anesthetized with ketamine, an antagonist of the N
      methyl-D-aspartate (NMDA) subclass of EAA receptors. The present experiments were
      therefore designed to investigate the influence of EAA administration within the
      NTS on the swallowing motor activity of rats anesthetized with ketamine. Pressure
      microinjections of GLU in doses ranging from 25 to 500 pmol elicited swallowing.
      This effect was dose-dependent and was not reproduced when control injections of
      the vehicle solution were performed. Microinjections of the GLU agonists,
      quisqualate (QUIS) and NMDA, in doses ranging between 2.5 and 50 pmol, also
      induced swallowing motor activities. QUIS, like GLU, elicited a short series of
      swallows at a brief latency while NMDA generated long-lasting rhythmic swallowing
      with a longer latency. Swallowing induced by GLU microinjections (100 pmol) was
      suppressed almost completely by local pretreatment with either the broad spectrum
      EAA receptor antagonist, gamma-D-glutamylglycine (250 pmol), or the more
      selective non-NMDA antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (50-100
      pmol), but not by pretreatment with the selective NMDA antagonist, DL-2-amino-5
      phosponovalerate (250 pmol). On the other hand, pretreatment with DL-2-amino-5
      phosphonovalerate (50 pmol) suppressed the deglutitions induced by NMDA
      microinjections (10 pmol) but not those elicited by QUIS microinjections (10
      pmol).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1981563
TI  - NMDA receptor antagonists reduce medial, but not lateral, perforant path-evoked
      EPSPs in dentate gyrus of rat hippocampal slice.
AB  - NMDA receptor antagonists produced differential effects on medial and lateral
      perforant path-evoked excitatory postsynaptic potentials (EPSPs) recorded in the
      dentate gyrus molecular layer of hippocampal slices. D-(-)-2-amino-5
      phosphonovaleric acid (D(-)-APV) and 3[(+/-)-2-carboxypiperazin-4-yl]-propyl-1
      phosphonic acid (CPP) significantly reduced the peak amplitude and total area,
      but not the initial negative slope, of the medial perforant path-evoked EPSP.
      Neither antagonist affected any component of the lateral perforant path-evoked
      EPSP. In contrast, population spikes evoked by stimulation of either pathway were
      depressed.

PMID- 1981565
TI  - Cutaneous manifestations of Takayasu arteritis. A retrospective study of 80
      cases.
AB  - The aim of this retrospective study is to delineate in Europe the frequency and
      type of cutaneous manifestations associated with Takayasu arteritis (TA). Eighty
      patients with TA were analyzed. Symptoms suggestive of Raynaud's syndrome were
      noted in 11 patients (14%) and could be directly related to large vessel
      involvement. Other skin lesions were observed in 10 patients (12.5%). Five had
      acute tender erythematous nodules on the legs with a clinical diagnosis of
      erythema nodosum; 2 had subacute ulcerated nodules of the legs; 1 had pyoderma
      gangrenosum-like ulcerations of the four limbs which resulted from the breakdown
      of subcutaneous nodules; 1 had lupus-like malar flush, and the last one had
      urticarial lesions with livedo reticularis. Skin samples were obtained from 4
      patients. Three of them agreed that reiterated biopsies be done on recurrent
      lesions. A granulomatous vasculitis was observed in 2 cases involving hypodermal
      arterioles in one case and veins in the other. The other pathological findings
      were septal and lobular panniculitis which can be associated with granulomatous
      vasculitis. Different histological findings on reiterated biopsies were
      frequently found. The absence of any other etiology and chronological arguments
      suggested a relationship between these skin lesions and TA. Tuberculosis was
      probable in 1 case but apparently was not related to the skin lesions.

PMID- 1981566
TI  - An introduction to the functional neurochemistry of the auditory system.
AB  - Neurochemistry of the auditory system has become one of the fastest growing areas
      in the study of audition. Many recent advances have implications for not only the
      basic auditory researcher but also the clinician. This article introduces some of
      the fundamentals of auditory neurochemistry as well as some recent developments.
      Also highlighted are some of the studies that appear to have current and future
      clinical significance.

PMID- 1981564
TI  - Neonatal dopamine lesion in the rat results in enhanced adenylate cyclase
      activity without altering dopamine receptor binding or dopamine- and adenosine
      3':5'-monophosphate-regulated phosphoprotein (DARPP-32) immunoreactivity.
AB  - Newborn male Sprague-Dawley rats were treated neonatally with an intracisternal
      injection of 75 micrograms 6-hydroxydopamine (6-OHDA) following desipramine
      pretreatment in order to induce a permanent selective dopamine (DA) lesion. At 60
      70 days of age a massive loss of tyrosine hydroxylase (TH) immunoreactive (IR)
      cells was seen in substantia nigra. The TH-IR terminal density was reduced by 92%
      in striatum, 77% in nucleus accumbens and by 72% in tuberculum olfactorium.
      Quantitative autoradiography using 3H-SCH-23390 and 3H-spiperone did not reveal
      any alteration of DA D1 and D2 receptor binding in the denervated regions
      studied. Furthermore, no change in the Bmax or Kd of 3H-SCH-23390 or 3H-spiperone
      in vitro binding was observed in membrane preparations of striatum following the
      neonatal DA lesion. Basal and DA-stimulated accumulation of cAMP was increased in
      striatal membrane preparations of the neonatally DA-lesioned rats. No alteration
      of the immunoreactivity of the D1 receptor associated phosphoprotein dopamine-
      and adenosine 3':5'-monophosphate-regulated phosphoprotein (DARPP-32), was
      observed as visualized using quantitative immunohistochemistry. Thus, neonatal DA
      lesions seem to induce a selective functional supersensitivity reflected by an
      enhanced activity of D1 receptor-coupled adenylate cyclase, without any
      alteration in the number of affinity of D1 and D2 receptor sites. Furthermore,
      the appearance of DARPP-32 seems to be independent of intact DA input during
      development.

PMID- 1981567
TI  - [Interactions between gastrointestinal epithelial cells and immune system cells].

PMID- 1981568
TI  - In vitro responses of rainbow trout (Oncorhynchus mykiss) somatotrophs to carp
      growth hormone-releasing factor (GRF) and somatostatin.
AB  - To study the hypothalamic control of growth hormone (GH) release in lower
      vertebrates, we employed an in vitro technique using a monolayer cell culture
      system of rainbow trout pituitary glands. Two newly purified carp brain growth
      hormone-releasing factors, carp GRF(1-45) and carp GRF(1-29), and synthetic
      somatostatin-14 (SST-14) were applied to the cultured pituitary cells. The
      results indicate that: (1) The carp GRFs had a dose-related potency in
      stimulating growth hormone release. The dose of half maximum effect (ED50) for
      carp GRF(1-45) was 0.107 nM, and an equal potency for carp GRF(1-29) was 0.388
      nM. (2) SST-14 inhibited GH release having a dose-dependent potency with an ED50
      of 0.186 nM. (3) Osmotic pressure did not influence SST-14 inhibited GH secretion
      but did affect spontaneous GH release. (4) The response of cultured cells was not
      affected by length of incubation period with SST-14 or carp GRF but was affected
      by cell density.

PMID- 1981569
TI  - [Ser5]-somatostatin-14: isolation from the pancreas of a holocephalan fish, the
      Pacific ratfish (Hydrolagus colliei).
AB  - The holocephalan fishes were the first class of vertebrate in evolution to
      develop a pancreatic gland with both endocrine and exocrine parenchyma. An
      extract of the pancreas of one such fish, the Pacific ratfish (Hydrolagus
      colliei) contained somatostatin-like immunoreactivity (141 pmol/g wet wt),
      measured with an antiserum raised against mammalian somatostatin-14. Automated
      Edman degradation and fast atom bombardment-mass spectrometry established the
      primary structure of the major molecular form as Ala-Gly-Cys-Lys-Ser-Phe-Phe-Trp
      Lys-Thr-Phe-Thr-Ser-Cys. A minor component of somatostatin-like immunoreactivity,
      constituting 8% of the total, was of approximate molecular weight 6000. Thus, in
      the ratfish pancreas prosomatostatin-I is processed predominantly to somatostatin
      14, as in the mammalian pancreas, but the resulting tetradecapeptide contains the
      substitution Ser for Asn at position 5.

PMID- 1981570
TI  - [Alpha interferon in oncohematology: update and perspectives. Report of a
      congress. 15 April 1989, Pavia, Italy].

PMID- 1981571
TI  - [Rational basis for the use of alfa-2a recombinant interferon in the treatment of
      mycosis fungoides (MF)].

PMID- 1981573
TI  - Neuropeptides in cutaneous neurofibromas of von Recklinghausen's disease.
AB  - The occurrence of neuropeptides was studied in neurofibromas of von
      Recklinghausen's disease by indirect immunofluorescence. All non-plexiform
      cutaneous neurofibromas contained abundant vasoactive intestinal polypeptide,
      peptide histidine-isoleucine and calcitonin gene-related peptide immunoreactive
      nerves. The nerves were small and unmyelinated. Neuropeptides might be
      responsible for itch that occurs especially in small cutaneous neurofibromas.
      Neuropeptides are also suggested to act as modulators and/or trophic factors for
      neurofibroma growth.

PMID- 1981572
TI  - Receptors for the Fc portion of immunoglobulins (FcR) on murine oral mucosal T
      cells.
AB  - The incidence and distribution of immunoglobulin receptors on oral mucosal T
      cells were investigated. Enrichment of either Thy-1.2, L3T4 or Lyt-2.2-positive
      cells was achieved by the use of a panning procedure following cell extraction by
      an optimized digestion method that preserved all three T-cell markers. The
      percentage of cells possessing Fc receptors was determined by using
      immunoglobulin-coated (IgM, IgG or IgA) fluorescent microspheres in a multipoint
      rosetting assay. We report that approximately 60% of Thy-1.2, L3T4 and Lyt-2.2
      positive cells bear Fc gamma R whereas less than 5% of T cells of any subset bear
      Fc alpha R or Fc mu R. In frozen tissue sections, Fc gamma R+ cells were mainly
      scattered throughout the basal and suprabasal epithelium and were observed at a
      lower frequency in the minor salivary gland network. From their distribution, it
      is anticipated that Fc gamma R+ cells may be involved in the surveillance of the
      epithelium while the minor Fc alpha R+ L3T4+ T lymphocyte population may promote
      the expression of sIgA by resident sIgM-bearing B cells, and their
      differentiation into IgA plasma cells.

PMID- 1981574
TI  - Positron emission tomography studies of neurotransmitter systems.

PMID- 1981576
TI  - Bladder cancer screening in high-risk groups. Proceedings of the international
      conference. September 13-14, 1989.

PMID- 1981575
TI  - Multiple site optical recording of transmembrane voltage (MSORTV), single-unit
      recordings, and evoked field potentials from the olfactory bulb of skate (Raja
      erinacea).
AB  - 1. Multiple site optical recording of transmembrane voltage (MSORTV), together
      with conventional extracellular electrophysiological techniques were utilized
      with in vivo and in vitro preparations of the olfactory bulb of the Atlantic
      skate Raja erinacea to analyze electrical activity simultaneously in layers deep
      to the glomerular layer. 2. In the living animals and the in vitro isolated
      olfactory bulb, orthodromic stimulation evoked a compound action potential in the
      olfactory nerve fibers, followed by a series of early field-potential waves (N1,
      P1, N2, P2, N3, and N4). During paired stimulation experiments, unusual patterns
      of facilitation and suppression were observed for the N2 wave. 3. After
      orthodromic stimulation, single units, presumably mitral/tufted cells, exhibited
      a period of early discharge, followed by a period of suppression of spontaneous
      activity and of their test response in a pair stimulation paradigm. Some neurons
      also exhibited a labile period of reexcitation that was accompanied by a late
      surface negative field potential; these responses were also present in olfactory
      bulb slices. 4. Extrinsic absorption changes obtained from 500-microns saggital
      slices of the olfactory bulb, stained with the pyrazooxonal dye RH-155, consisted
      mainly of two types of depolarizing responses, a fast and a slow component,
      followed under some conditions by a late hyperpolarization. All signals exhibited
      wavelength dependences typical of the action spectrum of RH-155 and were
      abolished in the presence of tetrodotoxin (TTX) or high K+ in the bath. 5. The
      fast component of the optical signal represents synchronous compound action
      potentials conducted by the olfactory nerve fibers or evoked in the mitral/tufted
      somata and axonal pathways. The slow depolarizing optical signal appeared, after
      orthodromic stimuli, mainly in the zone between the glomeruli and the
      mitral/tufted layer; barium (1-10 mM), which depolarizes glial cells, increased
      its size and duration, suggesting that this signal does not reflect a glial
      response to [K+]o. 6. Different condition/test (C/T) intervals produced partial
      or complete suppression of the test response, depending on the recording site and
      the stimulus intensity. Just threshold orthodromic stimuli evoked an intermediate
      period of facilitation of the slow signals. A similar period was also observed in
      the N2 wave of the field potential. 7. Calcium channel blockers such as cadmium
      ion, or a low Ca2+ medium, suppressed the slow optical component whether evoked
      by orthodromic, antidromic, or direct stimulation. gamma-Aminobutyric acid (GABA)
      and baclofen also reduced or blocked the slow component of the extrinsic
      absorption signal.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1981577
TI  - The parenteral controlled release of liposome encapsulated chloroquine in mice.
AB  - Free (0.6 mg), and liposome encapsulated chloroquine (0.6, 3 mg), were injected
      intraperitoneally, intramuscularly and subcutaneously in mice. Intraperitoneal
      administration of liposome-encapsulated chloroquine resulted in high and long
      lasting concentrations of chloroquine in the blood compared with intraperitoneal
      administration of free chloroquine. After administration of the liposome
      encapsulated chloroquine the concentrations in the spleen were also higher,
      indicating that chloroquine liposomes reached the blood compartment intact after
      intraperitoneal administration. After intramuscular and subcutaneous
      administration the chloroquine liposomes acted as a local depot, giving a slower
      release from the subcutaneous fat layer than from the muscle depot. After the 0.6
      mg dose a burst effect was found at about 7 h in most of the animals; this was
      not found after the 3 mg dose. This finding and the slower release after the 3 mg
      dose than after the 0.6 mg dose could be explained by the formation of aggregates
      after the injection.

PMID- 1981578
TI  - AHR-15010--a novel anti-arthritic agent.
AB  - AHR-15010 (3-(2-methoxyphenoxy)-1,2-propanediol bissulphamate ester) is a
      compound of novel structure that displays anti-arthritic activity in adjuvant
      arthritis in rats. When given orally from days 18 through day 50, (excluding
      weekends) after adjuvant injection, AHR-15010, at doses of 3.16 to 100 mg kg-1,
      produced significant anti-inflammatory activity and reduced the severity of the
      hind paw joint lesions as monitored by X-ray analysis. AHR-15010, however, has no
      acute anti-inflammatory activity in the Evans Blue-carrageenan pleural effusion
      assay in rats, has no analgesic activity in mice, and has no activity in a
      classic, delayed-type, hypersensitivity assay in mice or in a cotton pellet
      granuloma test in rats. These data, in conjunction with biochemical data showing
      that AHR-15010 has no prostaglandin synthetase inhibiting activity suggest that
      AHR-15010 is an anti-arthritic with a unique mechanism of action. AHR-15010 is a
      carbonic anhydrase inhibitor. Data are presented that suggest that AHR-15010 and
      acetazolamide, a prototype carbonic anhydrase inhibitor, may present novel
      approaches to the treatment of arthritis.

PMID- 1981579
TI  - Enhancement of morphine clearance following intravenous administration by oral
      activated charcoal in rabbits.
AB  - A single dose of activated charcoal (10 g) significantly reduced the half-life of
      elimination (1.02 +/- 0.10 and 0.70 +/- 0.04 h for the control and treated
      groups, respectively) and mean residence time (1.01 +/- 0.12 and 0.76 +/- 0.05 h
      for the control and treated groups, respectively) of morphine in rabbits. A 40%
      increase in the systemic clearance (85.73 +/- 7.72 and 122.64 +/- 16.32 mL min-1
      kg-1 for the control and treated groups, respectively) and a 30% decrease in AUC
      (204.38 +/- 22.20 and 140.03 +/- 19.32 micrograms h L-1 in the control and
      treated groups, respectively) were also noted. Charcoal administration did not
      significantly alter the volume of distribution (Varea and Vss) or the apparent
      distribution half-life. A two-compartment model adequately described morphine
      kinetics in control and treated rabbits; charcoal administration produced a
      significant increase in the tissue compartment rate constant (K21). This finding
      indicates that activated charcoal not only enhances the systemic elimination of
      morphine, but also accelerates the rate of transfer of morphine from the tissue
      compartment to the central compartment.

PMID- 1981580
TI  - Prostaglandin E2-mediated stimulation of mucus synthesis and secretion by rhein
      anthrone, the active metabolite of sennosides A and B, in the mouse colon.
AB  - Rhein anthrone, the active metabolite of sennosides A and B, stimulated PGE2
      release into the mouse colonic lumen. At 6.24 mg kg-1, it decreased net water and
      Na+ absorption significantly in the case of water, but could not reverse the net
      absorption in mouse ligated colon, although it enhanced net K+ secretion.
      Pretreatment with indomethacin diminished the effects of rhein anthrone except on
      K+ net secretion. Rhein anthrone or PGE2 markedly stimulated mucus secretion and
      synthesis in mouse ligated colon. The enhanced mucus secretion and synthesis
      induced by rhein anthrone were significantly suppressed by pretreatment with
      indomethacin. Our results have shown that the colonic secretion of water and
      electrolytes mediated by PGE2 is partly involved in the rhein anthrone-induced
      diarrhoea but that in mice, the mucoid diarrhoea induced by rhein anthrone
      results mainly from PGE2-mediated mucus synthesis and secretion in the colon.

PMID- 1981581
TI  - Effects of fedotozine on gastrointestinal motility in dogs: mechanism of action
      and related pharmacokinetics.
AB  - The effects of fedotozine, (+)-(1R)-1-phenyl-1-[(3,4,5
      trimethoxy)benzyloxymethyl]-N,N-dim eth yl- n-propylamine, on motility of the
      antrum and small intestine were investigated in dog. In fasted dogs, following
      i.v. administration, fedotozine at 1 and 2 mg kg-1 stimulated and at 5 mg kg-1
      inhibited antral motility. Between 1 to 5 mg kg-1, fedotozine exhibited a
      sustained and potent stimulatory effect on the small intestine inducing 1 to 4
      phases III of the migrating motor complex (MMC) lasting up to 32 min in the
      duodenum and migrating to the jejunum. Following oral administration, fedotozine
      at 2.5 and 5 mg kg-1 constantly stimulated both antrum and small intestinal
      motility. In fed dogs, fedotozine i.v. (2 mg kg-1) increased antral motility and
      induced phase III of MMC in the place of postprandial pattern. Naloxone (0.3 mg
      kg-1 i.v.) and naloxone methylbromide (2 mg kg-1 i.v.) inhibited the stimulatory
      effects of fedotozine on gastrointestinal motility indicating a peripheral opiate
      site of action of the drug whereas phentolamine, hexamethonium, propranolol and
      methysergide were inactive. In-vitro fedotozine showed submicromolar affinity for
      opiate receptors with a weak specificity for the mu-receptors in guinea-pig brain
      and myenteric plexus preparations. Plasma concentrations in dogs receiving
      fedotozine administered orally at 2.5 mg kg-1 (and in all dogs except one at 5 mg
      kg-1) were below the detection limit (less than 20 ng g-1). In contrast, tissue
      concentrations in the muscle and mucosal layers of the gut were above 1 microgram
      g-1.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1981582
TI  - A comparison of the effects of an extract of feverfew and parthenolide, a
      component of feverfew, on human platelet activity in-vitro.
AB  - Extracts of the herb feverfew inhibit human blood platelet aggregation and
      secretion induced by a number of agents in-vitro and this may relate to the
      beneficial effects of feverfew in migraine. We previously identified several
      compounds with antisecretory activity in human blood platelets using adrenaline
      as the stimulant. In the present study, we have compared the inhibitory activity
      of one of these compounds, parthenolide, with that of crude feverfew extract. The
      effects of both on [14C]5-HT secretion from platelets and on platelet aggregation
      induced by a number of different stimulants were determined. The activating
      agents studied included the phorbol ester PMA, ADP, arachidonic acid, collagen,
      the thromboxane mimetic U46619, the calcium ionophore A23187, the diacylglycerol
      analogue OAG and adrenaline. The results show that there are marked similarities
      between the effects of feverfew extract and of parthenolide on both [14C]5-HT
      secretion and platelet aggregation, which is consistent with the effects of
      feverfew extract on platelets being brought about by parthenolide or similar
      compounds in the extract. Only in one case, when A23187 was used as the
      stimulatory agent, was there any discrepancy, which may have been due to
      materials in the extract other than parthenolide. Both feverfew extract and
      parthenolide were more effective as inhibitors of the [14C]5-HT secretion and
      aggregation induced by some agents and not others, and were most effective as
      inhibitors of the [14C]5-HT secretion (but not the aggregation) induced by PMA.
      This suggests that the effects of feverfew/parthenolide on the protein kinase C
      pathway warrants further study.

PMID- 1981583
TI  - Effect on cerebral blood flow of orally administered indomethacin-loaded
      poly(isobutylcyanoacrylate) and poly(DL-lactide) nanocapsules.
AB  - Nanocapsules, containing indomethacin, were prepared either by interfacial
      polymerization of isobutylcyanoacrylate monomers or by interfacial deposition of
      a performed (DL-lactide) polymer. In-vitro release of indomethacin from
      nanocapsules was dependent on the pH of the sink solution and was enhanced by
      addition of albumin. A decrease in cerebral blood flow was noted 15 min after
      oral administration to rats of indomethacin nanocapsules (5 mg kg-1) and lasted
      over 3 h. Empty nanocapsules had no effect. Since release of indomethacin from
      nanocapsules is unlikely to occur in the lumen of the stomach, due to unsuitable
      pH conditions, and nanocapsules have been previously shown to be able to cross
      the intestinal barrier, to reach the villi vessels intact and to protect against
      the ulcerating effect of the free drug, it is suggested that the rapid onset of
      the pharmacological effect was sufficiently induced by free indomethacin released
      in the plasma following absorption of the intact nanocapsules.

PMID- 1981585
TI  - A pharmacodynamic model to predict the time dependent adaptation of dopaminergic
      activity during constant concentrations of haloperidol.
AB  - The concentration-response relationship of the accumulation of brain homovanillic
      acid (HVA) has been studied by giving rats a shorter (12 h) and a longer (76 h)
      constant intravenous infusion of haloperidol, respectively, at rates aiming at
      different steady state blood concentrations of haloperidol of 5 to 30 ng mL-1.
      The observed response on brain HVA concentration vs increasing steady state blood
      concentration of the drug produced a bell-shaped type of curve during the 12 h
      infusion. When the infusion proceeded for 76 h a similar type of curve was
      obtained but it was shifted downwards compared with the 12 h infusion. The
      dopaminergic activity of the rat brain, as reflected by the HVA levels, therefore
      adapted to a lower activity during the prolonged exposure to haloperidol. To
      follow the time course of this adaptation, one steady state level of about 12 ng
      mL-1 was established and kept for 12, 28, 52 and 76 h. The result showed that the
      accumulation of brain HVA decreased over time compared with control animals given
      placebo. A pharmacodynamic model was set up to quantitatively describe the time
      dependent adaptation of HVA accumulation in the whole rat brain during constant
      haloperidol administration. By fitting this model to all three sets of
      experimental data simultaneously, an adaptation half-time of about 38 h +/- 14
      (s.d.) and a tolerance potency of about 7 ng mL-1 were obtained which could be
      used to calculate that, for example, at a constant blood level of 10 ng mL-1
      haloperidol over 5 days the accumulation of brain HVA decreased by approximately
      91% of the maximal decrease.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1981584
TI  - Preferential decrease in dopamine utilization in prefrontal cortex by zopiclone,
      diazepam and zolpidem in unstressed rats.
AB  - This study has compared the effects of a cyclopyrrolone, zopiclone, a
      benzodiazepine, diazepam, and an imidazopyridine, zolpidem, on dopamine (DA) and
      DOPAC levels, and DA utilization (DOPAC/DA ratio) in rat striatum and prefrontal
      cortex. The endogenous levels of DA were significantly increased by both
      zopiclone (2.5, 10 and 40 mg kg-1 p.o.) and diazepam (10 and 40 mg kg-1 p.o.) in
      the prefrontal cortex, whereas striatal DA content was significantly increased
      only with the highest dose of diazepam (40 mg kg-1 p.o.). Diazepam (10 and 40 mg
      kg-1 p.o.) decreased cortical level of DOPAC more markedly than striatal levels,
      whereas zopiclone (40 mg kg-1 p.o.) only slightly decreased striatal DOPAC
      levels. Zopiclone and diazepam dose-dependently decreased DA utilization, an
      effect which was more marked in prefrontal cortex than in striatum. This result
      was confirmed with zolpidem, another benzodiazepine ligand. Zopiclone was most
      potent at decreasing DA utilization at the cortical level. The diazepam-induced
      decreases in DA metabolism and utilization were antagonized by Ro 15-1788,
      suggesting that the effects seen were mediated by specific benzodiazepine
      receptors. Thus, our results clearly show that ligands acting on the
      benzodiazepine receptor GABA receptor chloride ionophore complex can decrease the
      utilization of dopamine in unstressed rats. The preferential decrease in cortical
      DA utilization induced by benzodiazepine ligands may be compared to the well
      known activation by stress of the mesocortical DAergic system.

PMID- 1981586
TI  - The use of enzyme-linked immunosorbent assays to study the plasma disposition of
      sheep polyclonal and rat monoclonal digoxin-specific Fab fragments in the rabbit.
AB  - The plasma disposition of sheep polyclonal digoxin-specific Fab (fragment antigen
      binding) fragments has been studied in rabbits after their intravenous injection
      (1 mg kg-1) using enzyme-linked immunosorbent assays exploiting both the species
      specificity (ELISA1) and the digoxin-specificity (ELISA2) of digoxin-specific Fab
      fragments. The log concentration versus time profiles were best described by a
      biexponential plasma disposition when either assay was used. Although the plasma
      concentrations determined by ELISA1 and ELISA2 at each sampling time were not
      significantly different, there was a tendency for certain ELISA2 values to be
      higher. This resulted in the ELISA2-derived data giving a significantly longer
      distribution half-life (t1/2 alpha), but similar values for elimination half-life
      (t1/2 beta), apparent volume of distribution at steady state (Vdss), and
      clearance. Using ELISA2, which was generally the more sensitive assay, to compare
      the plasma disposition of the sheep polyclonal digoxin-specific Fab fragments
      with rat monoclonal digoxin-specific Fab fragments, it was shown that the rat
      product had a shorter t1/2 alpha (11 vs 22 min), a t1/2 beta which was not
      significantly different (253 vs 168 min), but a faster clearance (1.2 vs 0.7 mL
      kg-1 min-1), associated with a much larger Vdss (321 vs 108 mL kg-1). The
      extracellular fluid volume, using thiocyanate as a marker, was about 216 mL kg-1
      for the nine rabbits used. This suggests that the rat preparation penetrates more
      extensively into the extracellular space and may indicate that some degree of
      extracellular binding or cell penetration is occurring.

PMID- 1981587
TI  - The effects of haematocrit, plasma protein concentration and temperature of drug
      containing blood in-vitro on the concentrations of the drug in the plasma.
AB  - Factors which influence the plasma drug concentrations in whole blood have been
      investigated in-vitro using human blood containing radio-labelled phenytoin or
      chlorpromazine. Phenytoin (3.55 micrograms mL-1, 0.01 mM) or chlorpromazine (2.74
      micrograms mL-1, 0.01 mM) was mixed with normal or modified blood and the plasma
      drug level was measured. Plasma phenytoin and chlorpromazine levels decreased
      with decrease in the protein concentration of plasma, but were not influenced by
      addition of gamma-globulin to the blood specimen. Plasma phenytoin levels
      increased with an increase in haematocrit from 20 to 45%, whereas the
      chlorpromazine level remained constant. The partition coefficients of phenytoin
      and chlorpromazine between blood cells and plasma were almost the same at various
      haematocrit values. By cooling the blood containing each drug to 4 degrees C,
      plasma phenytoin and chlorpromazine levels were higher compared with those at 37
      degrees C. Similar temperature effects on the drug levels in plasma were obtained
      when the washed erythrocytes were resuspended in albumin medium, but not when
      resuspended in saline.

PMID- 1981588
TI  - Effect of structural variations of non-ionic surfactants on surface properties:
      surfactants with semi-polar hydrophobes.
AB  - The surface properties of a series of non-ionic surfactants in which a polar
      group (either an ether or a keto group) has been introduced into a hydrocarbon
      chain of octadecylpolyoxyethylene glycol monoether (C18E17-19) have been
      investigated. Surface tension measurements indicated that the critical micelle
      concentrations for these semi-polar surfactants in aqueous solution were all
      significantly higher than those of C18E22, the corresponding unsubstituted
      octadecylpolyoxyethylene glycol monoether. The minimum areas per molecule of the
      semi-polar surfactants in the surface monolayer were all larger than the area
      obtained for C18E22, from which it was concluded that the hydrophobe, and not the
      polyoxyethylene chain was the main determinant of surface area.

PMID- 1981589
TI  - Differential scanning calorimetry characterization of process-induced variations
      in an ointment base.
AB  - Preparation of an experimental emollient wax-gelled ointment base by two
      processes differing only in cooling rate produced material with markedly
      different physical properties. Differential scanning calorimetry showed that a
      major endotherm, possibly related to a phase change in a major triglyceride wax
      component, Synchrowax HGLC, was different in the two products. Mean enthalpies
      for this major endotherm for the two products were 7.36 J g-1 (s.d. = 0.49, n =
      5) in slow cooled samples and 4.35 J g-1 (s.d. = 0.21, n = 5) in fast cooled
      samples. The degree of order of the Synchrowax HGLC in the ointment is suggested
      as being different in the two preparations and it is this that controls the
      physical properties of the ointment.

PMID- 1981590
TI  - Desipramine and nortriptyline antagonize apomorphine and reserpine hypothermia by
      a different mechanism.
AB  - The reversal of hypothermia, induced by reserpine or by a high (16 mg) dose of
      apomorphine, in male Swiss mice, does not seem to utilize a common mechanism.
      Desipramine (20 mg kg-1 i.p., 60 min) or nortriptyline (8 mg kg-1 i.p., 60 min)
      increased temperature in both reserpine (2.5 mg kg-1 s.c., 18-19 h) and
      apomorphine (16 mg kg-1 s.c., 30 min) treated mice. In apomorphine-treated
      animals the effect of both drugs was reversed by the mixed dopaminergic D1- D2
      antagonist haloperidol (1 mg kg-1 i.p., 90 min), the D1-receptor blocking drug
      SCH 23390 (0.05 mg kg-1 s.c., 30 min), the alpha 1-adrenoceptor blocking drugs
      prazosin (3 mg kg-1 s.c., 90 min) and phenoxybenzamine (20 mg kg-1 i.p., 65 min),
      the beta-adrenoceptor blocking drug (+/-)-propranolol (10 mg kg-1 i.p., 120 min),
      and the opioid antagonist naloxone (2 mg kg-1 i.p., 15 min). In contrast the
      selective D2-antagonist (+/-)-sulpiride (100 mg kg-1 i.p., 90 min), and the alpha
      2-antagonist yohimbine (2 mg kg-1 i.p., 75 min), failed to effect the reversal of
      apomorphine hypothermia brought about by desipramine or nortriptyline. Their
      temperature effects in reserpinized mice were not modified by any of the
      antagonists tested.

PMID- 1981591
TI  - In-vitro antibacterial activity of noxythiolin and taurolidine.
AB  - The minimum inhibitory concentrations (MIC) of noxythiolin and taurolidine were
      determined for strains of Staphylococcus aureus, Escherichia coli and Pseudomonas
      aeruginosa. Tests were performed in broth alone and in broth plus 25% v/v serum
      or 25% v/v urine. Inoculum density was either 10(3), 10(5) or 10(7) colony
      forming units per mL-1. Slight inoculum-dependent variation in the activity of
      both agents was observed for some, but not all, strains of P. aeruginosa and S.
      aureus. A more pronounced medium-dependent increase in activity was observed with
      both drugs, with up to 8-fold reduction of values for MIC when tested in the
      presence of serum or urine. These observations may help to clarify the disparity
      between the observed clinical efficacy of these agents and relatively poor in
      vitro activity when tested using conventional methods in synthetic media.

PMID- 1981592
TI  - Study on the histamine-like activity of guanfacine.
AB  - The effects of guanfacine have been studied on guinea-pig isolated atria and
      diethylstilboestrol-treated rat isolated uterus to determine whether it possesses
      histamine-like activity. Guanfacine produced a concentration-dependent negative
      chronotropic effect which was not modified by ranitidine (0.1 microM). In rat
      isolated uterus contracted by KCl, clonidine (5-5000 microM) produced
      concentration-dependent relaxation which was blocked by ranitidine (0.1 microM),
      but guanfacine only produced relaxation at high concentrations (100-1000 microM),
      and this was not affected by ranitidine (0.1 microM). It is concluded that
      guanfacine, unlike clonidine, does not produce effects due to activation of H2
      receptors in either guinea-pig atria or rat uterus.

PMID- 1981593
TI  - Comparative effects of (+)-propranolol and nonoxynol-9 on human sperm motility in
      vitro.
AB  - Using the modified transmembrane migration method to measure sperm motility, it
      was shown that the surfactant nonoxynol-9 alone, was twice as potent as (+)
      propranolol alone as a spermicidal agent. Addition of (+)-propranolol to
      nonoxynol-9 shifted the dose-response curve to the left of the curves for either
      component alone, and a surprising synergistic action was evident. These
      observations may form the basis for the development of a new advantageous topical
      contraceptive combination product.

PMID- 1981594
TI  - The importance of nucleus accumbens in nicotine-induced locomotor activity.
AB  - Bilateral injections of either nicotine (200 micrograms) or cytisine (30 or 60
      micrograms) into the nucleus accumbens elicited locomotor hyperactivity in rats.
      Pretreatment with mecamylamine (2 mg kg-1, s.c.) was effective in attenuating the
      stimulatory effect of either nicotine or cytisine. This study suggests that
      nicotinic agonists such as nicotine and cytisine produce their locomotor
      excitatory effects through stimulation of the mesolimbic dopaminergic pathway.

PMID- 1981596
TI  - The relative dependence of calcium antagonists and neuroleptics binding to brain
      and heart receptors on drug lipophilicity.
AB  - QSAR analysis of the binding of calcium antagonists to brain and heart tissue
      shows that relative binding to brain tissue increases with increasing
      octanol/water partition coefficients. A number of antischizophrenic drugs follow
      the same pattern.

PMID- 1981595
TI  - Frusemide potentiates acetylcholine and carbachol in contracting the rat urinary
      bladder.
AB  - The interaction between acetylcholine and carbachol, and frusemide, a loop
      diuretic, have been studied on the rat isolated urinary bladder strip
      preparation. Acetylcholine (4.36 x 10(-8) - 1.3 x 10(-6) M) and carbachol (5.5 x
      10(-8) - 6.9 x 10(-6) M) induced contractions and these were significantly
      potentiated by frusemide (3.02 x 10(-6) M). The ratio of EC50 in the absence of
      frusemide to EC50 in the presence of frusemide was 1.58 +/- 0.03 (s.e.m.) for
      acetylcholine and 1.86 +/- 0.14 for carbachol. Potentiation of acetylcholine and
      carbachol contractions by frusemide was not observed in tissues treated with
      hexamethonium (2.5 x 10(-5) M). Rhythmic contractions induced by frusemide alone
      were markedly reduced by hexamethonium (2.5 x 10(-5) M) and tetrodotoxin (10(-6)
      M) but they were not significantly reduced by atropine (1.7 x 10(-6) M). The
      result suggests that frusemide increases the sensitivity of the bladder to
      acetylcholine and carbachol, and that it may have a nicotinic stimulant effect on
      the bladder. This extra-renal action may contribute to its prompt diuretic
      property.

PMID- 1981597
TI  - [Novel phenoxyalkylamine derivatives. VI. Synthesis and alpha-blocking activity
      of alpha-[(phenoxyethylamino)propyl]-alpha-phenylacetonitrile derivatives].
AB  - alpha-[(Phenoxyethylamino)propyl]-alpha-(4-methoxyphenyl) acetonitrile
      derivatives possessing methyl, bromo, nitro, amino or various sulfonamide groups
      at 3-position on ring A and an alkoxy group on ring B were synthesized. Their
      alpha-blocking activities were tested. The activity of 5-[1-cyano-4-[[2-(2
      ethoxyphenoxy) ethyl]amino]-1-isopropylbutyl]-2-methoxy-benzenesulfonamide (15a)
      and 5-[1-cyano-4-[[2-(5-fluoro-2-methoxyphenoxy)ethyl] amino]-1-isopropylbutyl]-2
      methoxybenzenesulfonamide (15c) was close to that of prazosin, a typical alpha
      blocker. Structure-activity relationship of these derivatives is also stated.

PMID- 1981598
TI  - [Studies on the synthesis of condensed pyridazine derivatives. III. Synthesis and
      benzodiazepine receptor binding studies of condensed triazolopyridazine
      derivatives].
AB  - A series of 6H-(1)benzothiopyrano[3,4-e][1,2,4]triazolo[4,3- b]pyridazines and
      6,7-dihydro-(1)benzothiepino[4,5- e][1,2,4]triazolo [4,3-b]pyridazines were
      prepared and tested for their ability to displace [3H] diazepam from rat brain
      membranes. An approximately planar shape of these molecules was essential for
      high affinity to the benzodiazepine receptor. Among them, 11-aryl compounds in
      the latter series were found to have high affinity to the benzodiazepine
      receptor. 11-Phenyl- and 11-thienyl- 6,7-dihydro-(1)benzothiepino[4,5
      e][1,2,4]triazolo[4,3- b]pyridazine (3b-5 and 3b-11 respectively) showed the
      potent affinity comparable to that of diazepam. The structure-activity
      relationships are also discussed.

PMID- 1981599
TI  - Classical phenylketonuria in Bulgaria: RFLP haplotypes and frequency of the major
      mutations.
AB  - RFLP haplotypes and common mutations in the phenylalanine hydroxylase gene have
      been studied in a group of 29 Bulgarian PKU families. Haplotype distribution
      differs from that in other European populations, with a predominance of
      haplotypes 2 and 6 and a total absence of haplotype 3. The amino acid
      substitution in codon 408 is the most frequent molecular defect. The splicing
      defect in intron 12 is not found in Bulgarian PKU patients. Testing for three
      mutations, reported to be common among haplotype 1 and 4 alleles, has shown that
      they occur less frequently in Bulgarian PKU patients. Screening with five pairs
      of allele specific oligonucleotides failed to show the mutation in 59% of the
      patients. These findings add to the evidence that PKU is heterogeneous and that
      significant interpopulation differences exist. At present, DNA data cannot be
      used as an aid in early clinical classification and prognosis of
      hyperphenylalaninaemia in Bulgaria.

PMID- 1981600
TI  - [Significance of digital subtraction angiography for estimation of early results
      of myocardial revascularization after internal mammary artery grafting].
AB  - Between 1st January and 31st December 1987 126 consecutive patients underwent
      full myocardial revascularization using at least one internal mammary artery
      bypass grafting in Department of Cardiovascular Surgery of University of
      Freiburg. In 78 patients (75 males, 3 females) DSA was performed within 8 days
      after surgery to evaluate dynamics of IMA-graft. The age ranged from 38 to 67
      years (mean 53.4 years). DSA study was performed through the brachial artery,
      contrast medium was injected with flow of 10 ml/sec. in counter current. It was
      only one series of angiograms necessary to visualise flow from subclavian artery,
      through IMA to coronary artery. Among 78 investigated patients in 61 (78%) the
      distal anastomosis appeared to be widely patent and flow through the IMA and
      anastomosed coronary artery was sufficient. Patency of one of the branches of IMA
      or stenosis of IMA graft contributed to inadequate flow in 12 patients (15.6%).
      In 5 (6.4%) operated patients the IMA graft was not patent. Counter current
      intraarterial DSA requires much smaller amount of contrast medium than classical
      angiography, moreover avoiding of aortic catheterization with all risks involved.
      The counter current intraatrial DSA is an excellent technics of estimation of the
      flow to grafted coronary arteries. The method is easy to perform, repetitive and
      carry very small risk for the patient. Early postoperative evaluation of IMA
      graft patency is essential for estimation of effectiveness of myocardial
      revascularisation and prognosis for the patient.

PMID- 1981601
TI  - Mesangial cell accessory functions: mediation by intercellular adhesion molecule
      1.
AB  - Mesangial cell (MC) proliferation is an early pathologic alteration
      characteristic of many forms of immune mediated glomerulonephritis. The
      intracapillary position, contractile capacity, and production of cytokines and
      other inflammatory molecules place MC in a pivotal position to initiate, mediate,
      and direct glomerular damage. We as well as others have noted increased levels of
      cytokines including IFN gamma, TNF, and IL-1 and the cell surface MHC class II
      and ICAM-1 molecules in the kidneys of mice with lupus nephritis. MHC class II
      and ICAM-1 molecules are central to the interaction of T cells with antigen
      presenting cells (APC). Since cytokines can increase both MHC class II and ICAM-1
      molecules, we investigated whether mesangial cells could function as APC or
      accessory cells after cytokine stimulation. For these studies we established a
      permanent MC line through transformation with origin-deficient SV40 DNA. Surface
      expression of ICAM-1 was similar in untransformed MC as well as SV40 transformed
      MC from normal mice and in untransformed cells from mice with lupus nephritis.
      Basal expression of ICAM-1 was upregulated rapidly by IFN gamma, TNF, and IL-1.
      MHC class II expression could not be induced with TNF or IL-1 alone but required
      prolonged stimulation with IFN gamma. MC adhered and presented antigen to an
      antigen specific IaK restricted T cell hybridoma. Anti-ICAM-1 mAb decreased
      adhesion and antigen presentation of cytokine stimulated MC. By comparison, MHC
      class II mAb abrogated antigen presentation by MC bearing MHC class II but did
      not block adhesion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1981602
TI  - [Correction of postoperative disorders of the motor-emptying function of the
      digestive tract].

PMID- 1981603
TI  - An isometric method to study respiratory smooth muscle responses in mice.
AB  - An isometric method to measure the smooth muscle tone of murine tracheas in vitro
      was developed. Nine trachea rings from just beneath the larynx were prepared free
      of excess tissue with the help of a binocular microscope. These trachea parts
      were slipped onto supports in an organ bath containing Krebs' solution. Isometric
      tension was measured with a force displacement transducer connected to the upper
      trachea support, and is expressed as changes in grams force. The cholinergic
      agonist carbachol contracted isolated tracheas. Serotonin also induced
      contractions, but was less potent than carbachol. Histamine induced tracheal
      contractions only at very high concentrations. Sympathomimetic beta adrenergic
      agonists relaxed carbachol-precontracted tracheas with the following order of
      potency: isoprenaline (beta 1 and beta 2 adrenoceptor agonist) greater than
      salbutamol (beta 2 adrenoceptor agonist) greater than prenalterol (beta 1
      adrenoceptor agonist). Adrenaline and noradrenaline relaxed carbachol
      precontracted tracheas, with adrenaline being the more potent relaxant. For the
      study of airway reactivity, this mouse trachea model has several advantages over
      immunopharmacologic models: The immune system of the mouse has been characterized
      extensively, and many reagents are available to study the immune system and,
      thus, possible interactions of this system with pharmacological mechanisms. Other
      animal models used in pharmacology are generally less well defined
      immunologically.

PMID- 1981604
TI  - Isolation and primary culture of endocrine cells from canine gastric mucosa.

PMID- 1981606
TI  - [Anaerobic bacteria and their role in recurrent tonsillitis].
AB  - The presence of anaerobic bacteria in 100 palatal tonsils obtained during the
      tonsillectomy, was evaluated in quality and in quantity. 17 species of anaerobic
      bacteria were found. The most frequent were: Bacteroides melaninogenicus,
      Peptostreptococcus anaerobius, Peptostreptococcus intermedius, Propionibacterium,
      Veillonella parvula and Peptococcus asaccharolyticus. In most evaluations their
      density was 10(5)-10(6) in gram of tonsil tissue, sometimes 10(7). Its role in
      recurrent tonsils infections was discussed.

PMID- 1981605
TI  - Dispersed salivary gland acinar cell preparations for use in studies of
      neuroreceptor-coupled secretory events.

PMID- 1981607
TI  - Testicular descent: new insights into its hormonal control.

PMID- 1981608
TI  - [Recommendations of the All-Union Conference on Medico-Social Problems of
      Disability in Childhood (Leningrad, June 12-14, 1990)].

PMID- 1981609
TI  - [Significance of hyper-enzymuria in the diagnosis of paraspecific nephropathies
      in different tuberculosis localizations in children].

PMID- 1981610
TI  - [Neonatal hypoxic-ischemic nephropathy and urinary diagnostic indices: the
      utility of measuring tubular enzymes (NAG and AAP)].
AB  - Feto-neonatal hypoxia can cause a functional kidney impairment, which is often
      temporary and not clinically overt, but sometimes leading to acute renal failure.
      Hypoxic stress may result in a tubulo-interstitial damage, and kidney tubular
      enzymes determination has proved to be an easy, early, and non invasive method to
      define a tubular interstitial lesion. A major target of nephrotoxicity is the
      proximal tubular cell: alterations in brush-border membrane and cytoplasm result
      in increased turnover processes in the kidney cortex, following by a
      corresponding increased excretion of alanine-aminopeptidase (AAP) and N-acetyl
      glucosaminidase (NAG) from the proximal tubular cells, long before glomerular or
      tubular functions are impaired. AAP and NAG excretion is directly correlated with
      the strength and the duration of toxic alteration of the proximal tubule. NAG and
      AAP have been already studied in the adults and the children; they have been
      chosen for this investigation with a double aim: 1) to define the amount of their
      urinary excretion in relation with gestational age at birth; 2) to evaluate if in
      the newborn, independently of the gestational age, their urinary concentration
      may be increased by ischaemic conditions caused by hypoxia. We studied 52 healthy
      newborns (7 preterm of 33-36 weeks and 45 full-term) and 16 newborns with feto
      neonatal hypoxia (8 preterm of 26-36 weeks and full-term) at the forth day of
      life. Urinary NAG and AAP were assayed by colorimetric methods and the results
      expressed as mU/mg. creatininuria.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1981611
TI  - [LHRH and cryptorchism. The results in a selected group of patients].
AB  - The authors report their experience on treatment or cryptorchidism with synthetic
      LHRH intranasally sprayed in a selected group of prepubertal boys (58 cases with
      75 undescended testes). The success rate of the present study, in the patients
      with pretreatment testicular position at or below the external annulus, was 36%
      (24/66 testes). Indications for hormonal therapy are related to the position of
      the testis before treatment.

PMID- 1981612
TI  - Contemporary antifungal therapy: focus on fluconazole. Proceedings of a
      scientific symposium. October 20, 1989, Atlanta, Georgia.

PMID- 1981613
TI  - Classification for traumatic injuries to teeth for epidemiological purposes.

PMID- 1981614
TI  - Prescribing in epilepsy.

PMID- 1981616
TI  - Speculating about pyrazines.
AB  - Of the various types of alerting signals found in nature, odours are the least
      well understood. The worldwide distribution of pyrazines in plants, insects,
      terrestrial vertebrates, marine organisms, fungi and bacteria suggests that they
      are of special significance. We speculate that these molecules served as natural
      points of convergence in the evolution of widespread alerting signals, which are
      used for differing but related intraspecific purposes by various species. In
      aposematic, self-advertising toxic insects and their mimics, for example,
      pyrazines function as additional warning signals; preliminary data indicates that
      their odour can potentiate taste aversion learning in rats and the associative
      learning of immune suppression in mice. The latter suggests that in addition to
      their alerting properties, pyrazine odours may act as ectohormones which interact
      with predator physiology.

PMID- 1981615
TI  - Blood chemistry of human fetuses in the second and third trimesters.
AB  - Six biochemical parameters and four enzyme activities were determined from the
      serum of 76 healthy and 56 pathological human fetuses between the 20th and 38th
      week of pregnancy. In the normal fetuses studied within that period, creatinine,
      immunoglobulin M, lactate dehydrogenase, and gamma-glutamyltransferase increased;
      haemoglobin F and glucose progressively decreased; and alkaline phosphatase was
      at a peak around the 26th week; cholesterol and triglycerides were always low.
      The same parameters were also measured in some of the pathological fetuses and
      compared with their normal counterparts.

PMID- 1981617
TI  - Development of contrast sensitivity and acuity of the infant colour system.
AB  - We have monitored the development of infant colour vision by measuring chromatic
      contrast sensitivity and acuity in eight young infants over a period of 6 months.
      Steady-state visual evoked potentials (VEPS) were recorded in response to both
      chromatic (red-green) and luminance (red-black or green-black) patterns that were
      reversed in contrast over time. For most infants, no response could be obtained
      to chromatic stimuli of any size or contrast before 5 weeks of age, although
      luminance stimuli of 20% contrast gave reliable responses at that age. When
      responses to chromatic stimuli first appeared, they could be obtained only with
      stimuli of very low spatial frequency, 20 times lower than the acuity for
      luminance stimuli. Both contrast sensitivity and acuity for chromatic stimuli
      increased steadily, more rapidly than for luminance stimuli. As the spectral
      selectivities of infant cones are similar to those of adults, the difference in
      rate of development of luminance and chromatic contrast sensitivity and acuity
      stimuli probably reflects neural development of the infant colour system.

PMID- 1981618
TI  - Motion-boundary illusions and their regularization.
AB  - Humans use various cues to understand the structure of the world from images. One
      such cue is the contours of an object formed by occlusion or from surface
      discontinuities. It is known that contours in the image of an object provide
      various amounts of information about the shape of the object in view, depending
      on assumptions that the observer makes. Another powerful cue is motion. The
      ability of the human visual system to discern structure from a motion stimulus is
      well known and has a solid theoretical and experimental foundation. However, when
      humans interpret a visual scene they use various cues to understand what they
      observe, and the interpretation comes from combining the information acquired
      from the various modules devoted to specific cues. In such an integration of
      modules it seems that each cue carries a different weight and importance. We
      performed several experiments where we made sure that the only cues available to
      the observer were contour and motion. It turns out that when humans combine
      information from contour and motion to reconstruct the shape of an object in
      view, if the results of the two modules--shape from contour and structure from
      motion--are inconsistent, they experience a perceptual result which is due to the
      combination of the two modules, with the influence of the contour dominating,
      thus giving rise to the illusion. We describe here examples of such illusions and
      identify the conditions under which they happen. Finally, we introduce a
      computational theory for combining contour and motion using the theory of
      regularization. The theory explains such illusions and predicts many
      more.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1981620
TI  - The regulation of gastrointestinal helminth populations.
AB  - One quarter of the world's human population suffers infection with helminth
      parasites. The population dynamics of the ten or so species, which cause disease
      of clinical significance have been well characterized by epidemiological field
      survey. The parasites are in general highly aggregated between hosts, and their
      populations seem to be temporally stable and to recover rapidly from
      perturbation, including interventions designed to alleviate disease. This paper
      reviews current understanding of the population regulation of helminth species of
      medical significance. Both empirical (field and laboratory) and theoretical
      results are included, and we attempt to interpret the findings in the broader
      context of the population ecology of free-living species. We begin by considering
      the evidence for regulation from field data concerning the temporal stability of
      helminth populations within communities and from the results of perturbation
      experiments. The detection of regulatory processes is then discussed (with regard
      to statistical and logistical considerations), and the evidence from both the
      field and laboratory studies reviewed. Deterministic models are described to
      investigate the possible consequences of regulation imposed at different points
      in the parasite life-cycle. The causes and consequences of parasite aggregation
      are considered, and a stochastic model used to investigate the impact of
      different combination of regulatory processes and heterogeneity generating
      mechanisms.

PMID- 1981619
TI  - Sequence similarities between the gene specifying 1-phosphofructokinase (fruK),
      genes specifying other kinases in Escherichia coli K12, and lacC of
      Staphylococcus aureus.
AB  - The sequence was determined of the 936 nucleotides that compose the fruK gene of
      Escherichia coli K12, together with the final 310 bases of fruF and the initial
      224 bases of fruA, which flank fruK. These genes specify proteins that effect the
      uptake of fructose and its PEP-dependent conversion to fructose 1-phosphate (fruA
      and fruF), and the ATP-dependent phosphorylation of that product to fructose 1,6
      bisphosphate (fruK); together, these genes form the fruFKA operon. The deduced
      amino acid sequence of the fruK product exhibits little similarity to the major 6
      phosphofructokinase of E. coli (pfkA) and the 6-phosphofructokinases present in a
      number of pro- and eukaryotic organisms, but there is 27%, 25% and 22% identify
      of sequence respectively with the minor 6-phosphofructokinase (pfkB) of E. coli,
      the lacC gene product of Staphylococcus aureus and the ribokinase of E. coli.

PMID- 1981621
TI  - Distinguishing error from chaos in ecological time series.
AB  - Over the years, there has been much discussion about the relative importance of
      environmental and biological factors in regulating natural populations. Often it
      is thought that environmental factors are associated with stochastic fluctuations
      in population density, and biological ones with deterministic regulation. We
      revisit these ideas in the light of recent work on chaos and nonlinear systems.
      We show that completely deterministic regulatory factors can lead to apparently
      random fluctuations in population density, and we then develop a new method (that
      can be applied to limited data sets) to make practical distinctions between
      apparently noisy dynamics produced by low-dimensional chaos and population
      variation that in fact derives from random (high-dimensional) noise, such as
      environmental stochasticity or sampling error. To show its practical use, the
      method is first applied to models where the dynamics are known. We then apply the
      method to several sets of real data, including newly analysed data on the
      incidence of measles in the United Kingdom. Here the additional problems of
      secular trends and spatial effects are explored. In particular, we find that on a
      city-by-city scale measles exhibits low-dimensional chaos (as has previously been
      found for measles in New York City), whereas on a larger, country-wide scale the
      dynamics appear as a noisy two-year cycle. In addition to shedding light on the
      basic dynamics of some nonlinear biological systems, this work dramatizes how the
      scale on which data is collected and analysed can affect the conclusions drawn.

PMID- 1981622
TI  - The interplay of population dynamics and the evolutionary process.
AB  - Long-term maintenance of genetic diversity is affected by ecological forces that
      are driven in turn by current levels of genetic variation. The strength of
      population regulation and the consequent patterns of population fluctuations
      determine the likelihood of genetic changes considered pivotal for rapid
      speciation. However, genetic diversity in the susceptibility to regulatory forces
      can reduce the magnitude of such fluctuations and minimize the likelihood of
      genetic revolutions. A group of populations that experiences local extinctions
      and recolonizations may hold lower levels of genetic diversity than in the
      absence of such extinctions, but local adaption, which provides enhanced genetic
      diversity, can reduce the likelihood of local extinctions. Tightly regulated
      populations experience different selection pressures than poorly regulated
      populations, although tighter regulation itself can evolve. When genotypic
      variation affects the outcome of interspecific interactions on a local scale,
      this effect, coupled with appropriate spatial variation, can enhance the
      resilience of the interactive system.

PMID- 1981623
TI  - Serum amino acids, central monoamines, and hormones in drug-naive, drug-free, and
      neuroleptic-treated schizophrenic patients and healthy subjects.
AB  - Basal serum amino acids (including central monoamine precursors), central
      monoamines, and hormones were studied in schizophrenic patients (drug-naive; n =
      20; drug-withdrawn for 3 or more days, n = 67; neuroleptic-treated, n = 23) and
      healthy subjects (n = 90) to answer the following questions: (1) Do neuroleptic
      withdrawn and neuroleptic-naive patients differ on these serum measures? (2) What
      are the effects of neuroleptic treatment on these measures? (3) On which
      variables do drug-free and neuroleptic-treated patients differ? Because serum
      amino acid, central monoamine, and hormone levels were similar in drug-naive and
      drug-withdrawn patients, data from these groups ("drug-free") were combined and
      compared to those of healthy subjects and neuroleptic-treated patients.
      Asparagine, citrulline, phenylalanine, and cysteine were higher, while tyrosine,
      tryptophan, and the ratio of tryptophan to competing amino acids were
      significantly lower in drug-free schizophrenic patients than in healthy subjects.
      Dopamine was increased, and melatonin and thyroid hormones were decreased in drug
      free schizophrenic patients compared to healthy subjects. Norepinephrine,
      epinephrine, and prolactin were higher in neuroleptic-treated men compared to
      drug-free male patients or healthy men. These results are consistent with the
      hypothesis of dopaminergic overactivity in schizophrenia, which might be caused
      by altered amino acid precursor availability and could be related to the decrease
      in melatonin and reduction in thyroid hormone levels.

PMID- 1981624
TI  - [Synaptic transmission and cerebrovascular pathology].

PMID- 1981625
TI  - [The use of positron-emission tomography in psychiatry].
AB  - Positron-emission tomography (PET), a noninvasive analytical method, made
      possible the detection of regional alterations in the central nervous system,
      thus demonstrating "in vivo" the presence of biochemical alterations and the
      organization of cerebral function in the pathological states. The study of
      glucose cerebral metabolism velocity, performed recently with the aid of PET,
      reveals that in the patients with thymic disorders the values recorded for the
      bipolar syndromes differ from those recorded the for unipolar ones. At the same
      time, the direct measurement of the activity of the neuroanatomic structures
      involved in schizophrenia and their response to neuroleptics was possible. This
      technique and the F-fluoro-desixiglucose method were also applied to the patients
      with Alzheimer's disease, multi-infarct dementia, Huntington's disease. Wilson's
      disease and Parkinson's disease. Suggestive alterations of glucose metabolism
      velocity were noticed and the neuroanatomic structures involved in the
      pathological manifestations could be specified.

PMID- 1981627
TI  - Transactions of the XXII Nordic Congress in Clinical Chemistry. Trondheim, June
      25-28, 1990, Norway.

PMID- 1981626
TI  - [The cytochemical characteristics of neutrophilic leukocytes in the peripheral
      blood and synovial fluid of patients with rheumatoid arthritis in the course of
      treatment].
AB  - The authors studied the activity of alkaline and acid phosphatase (AP),
      myeloperoxidase (MP), the level of cationic protein (CP), spontaneous and
      pyrogenal-induced tests of restoration of nitroblue of tetrazolium (HCT-test) in
      the blood and synovial fluid (SF) neutrophils in 116 patients with rheumatoid
      arthritis (RA) in the dynamics of a 3-4-week and subsequent 6-month therapy with
      chrysanol, salazopyridazine and delagil. In the active phase all the patients
      exhibited an abrupt increase in the activity of alkaline and acid phosphatase in
      blood neutrophils, a drop in the level of CP (in 69%), a rise in the activity of
      MP (in 32%); pyrogenal did not induce any capacity for restoring HCT (in 44%).
      Indices of alkaline and acid phosphatase in blood and SF neutrophils and also of
      the induced TCT-test in blood neutrophils correlated with the degree of RA
      activity. Statistically significant positive cytochemical shifts were noted only
      after 6 months of treatment: a decrease in alkaline and acid phosphatase
      activity, a rise in the level of CP, MP and capacity for restoration pf HCT with
      pyrogenal in blood neutrophils. Increase in the correlation of CP or MP levels by
      0.2 or more in blood and SF neutrophils, and also of the normal level of CP in
      blood neutrophils or its increase not less than by 15% 3-4 weeks after the
      beginning of therapy evidence good prognostic informativeness with respect to the
      effectiveness of basic therapy.

PMID- 1981628
TI  - The 32nd SEAMEO-TROPMED Regional Seminar: primary health care as a participative
      approach in the improvement of the quality of life.

PMID- 1981629
TI  - Effectiveness of repellent/insecticidal bars against malaria and filariasis
      vectors in peninsular Malaysia.
AB  - Field tests were conducted to compare the degree of protection from bites of
      Mansonia species and Anopheles maculatus by applying two repellent/insecticidal
      bars, MOSBAR and MOSKIL, to exposed arms and legs. Human test subjects were
      exposed to natural populations of mosquitos for an 8-hour night time period while
      using the repellent/insecticidal bars. MOSBAR gave good protection against the
      bites of Mansonia and An. maculatus. MOSKIL was effective against An. maculatus
      but not against Mansonia. High mortality was observed among the mosquitos
      collected from human test subjects treated with the repellent/insecticidal bars.
      Use of MOSBAR in terms of cost-effectiveness and safety by field and health
      workers entering into malaria and filariasis endemic areas is discussed.

PMID- 1981630
TI  - A mark-release-recapture experiment with Mansonia mosquitos in Malaysia.
AB  - An experiment was carried out with Mansonia mosquitos in an area endemic for
      subperiodic Brugia malayi to assess the applicability of the mark-release
      recapture method to these mosquitos. An estimated 17,880 individuals of six
      species of Mansonia were marked with fluorescent dust and released: 453 Ma.
      annulata, 305 Ma. annulifera, 6,200 Ma. bonneae, 516 Ma. dives, 3,998 Ma. indiana
      and 6,408 Ma. uniformis. Twenty-three marked individuals were recaptured. Most
      recaptures were made one or two nights after their release, but one Ma.
      annulifera was recaptured five nights later and one Ma. bonneae had been marked
      and released 6-11 nights previously. The recaptured mosquitos were collected
      between 0.5 and 2.4 km from their release points.

PMID- 1981631
TI  - The effect of Bacillus thuringiensis israelensis [H-14] on emergence of Mansonia
      mosquitos from natural breeding habitat.
AB  - The measurement of the ultimate effects of the microbial insecticides on mosquito
      density is best obtained by assessment of adult populations. The main aims of
      this study are: (1) to assess the effect of Bacillus thuringiensis israelensis
      (Bti) FC Skeetal and Bactimos briquettes on the emergence rate of Mansonia
      bonneae developed from the introduced first-instar stage larvae and (2) to
      measure the effect of these two formulations of insecticides on Mansonia adult
      populations emerging from the natural breeding plots. Bti Skeetal and Bactimos
      briquettes at the lower applied dosages of 2.3 kg/ha and 1 briquette case/20 m2
      respectively achieved 39-40% pupation rates and 31.5-34.2% adult emergence rates.
      At these low applied dosages, there was little or no direct effect on pupation
      from the surviving larvae and thereafter on the emergence of adults from the
      pupae. A two-fold increase in dosage, however, produced a drastic decline in the
      pupation rate and adult emergence rate. The rates dropped to 6.5% (pupation) and
      4.3% (adult emergence) of the total larvae for Bactimos briquettes and to merely
      1.5% (pupation) and 1.3% (adult emergence) of the total larvae for Skeetal. In
      studying the effect of Bti on the field populations of Mansonia mosquitos, two
      plots each were treated with Bactimos at 1 briquette case/10 m2 and Skeetal at
      4.6 kg/ha. A wooden pyramid-shaped screened cage was placed on a cluster of host
      plants for a period of 2 weeks to trap the emerging adult mosquitoes. There were
      a total of 24 clusters of host plants in each plot.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1981632
TI  - Recommendations for action and research from a symposium and workshop on the
      complications, management and prevention of malaria. The Roche Asian Research
      Foundation.

PMID- 1981633
TI  - [Treatment of patients with chronic obstructive bronchitis and pulmonary
      hypertension during ambulatory care].

PMID- 1981634
TI  - A review of the clinical pharmacokinetics and metabolism of the alpha 1
      adrenoceptor antagonist indoramin.
AB  - 1. The alpha 1-adrenoceptor antagonist indoramin is rapidly and extensively
      absorbed after oral administration, but with only low to moderate bioavailability
      (8-24% median) from the tablet (Baratol). Although plasma protein binding is high
      (72-86%), the drug is widely distributed into tissues (with median Vz 6.3-7.7
      l/kg after i.v. dosage). 2. Elimination of indoramin is rapid in most healthy
      volunteers, with median plasma clearances of 18-26 ml/min per kg, after i.v.
      dosage. Elimination occurs principally by metabolism, the major route being
      indole 6-hydroxylation, followed by sulphate conjugation of 6-hydroxyindoramin.
      The faecal route of excretion predominates (45-50% of dose), with a further 35
      40% in the urine. 3. Extensive variation in single-dose oral pharmacokinetics of
      indoramin is due largely to the existence of a poor metabolizer phenotype which
      co-segregates with that of debrisoquine. 4. On repeated administration (37.5 mg
      twice daily) to healthy volunteers, plasma concentrations of indoramin accumulate
      3-4-fold above those anticipated from single-dose kinetics. However, steady state
      is achieved within the first week of dosing. 5. The pharmacokinetics of indoramin
      are substantially altered in the elderly. The oral AUC for a 50 mg dose is
      increased approx. 5-fold and the t1/2 2.5-fold. 6. Cirrhotic liver disease
      enhances bioavailability and decreases clearance, approx. 2-fold in each case for
      single oral and i.v. doses of 50 mg and 0.15 mg/kg respectively. 7. After oral
      indoramin Cmax and AUC are both raised (58% and 25%, respectively, for a 50 mg
      dose) by co-ingested ethanol (0.5 g/kg). After i.v. indoramin, kinetics are
      unaffected by alcohol, but indoramin (0.175 mg/kg) slightly increases (26%) blood
      ethanol concentrations during the first hour after dosing. 8. The
      pharmacodynamics of indoramin appear to be related to the combined
      pharmacokinetics of the drug and its 6-hydroxylated metabolite, which contributes
      to the antihypertensive effect.

PMID- 1981635
TI  - Bile secretion in man. The effects of somatostatin, vasoactive intestinal peptide
      and secretin.
AB  - In 41 patients, operated upon for common bile duct stones, a temporary bile
      fistula was achieved by means of a T-tube and a Foley-catheter with an occludable
      balloon. To learn more about peptide control of bile secretion, 6-8 days after
      surgery, bile flow was studied before as well as during infusion of the three
      peptides somatostatin, vasoactive intestinal peptide and secretin. The findings,
      also presented in Figure 17, were: 1. During somatostatin infusion, bile
      secretion decreased by 30%, and bile lipid output was reduced by some 10%. The
      clearance of [14C]-erythritol decreased by 25%, indicating an effect on the bile
      acid-dependent canalicular bile secretion (Paper I). 2. Vasoactive intestinal
      peptide (VIP) increased bile secretion by 65%. The concentration of bile lipids
      decreased, whereas the output was uneffected. The bicarbonate concentration
      increased, and the concentrations of sodium and potassium were uneffected. [14C]
      erythritol clearance was not influenced by VIP infusion. Thus, VIP stimulated
      bile secretion at the ductular level (Paper II). 3. VIP increased bile secretion
      by 60%, whereupon secretin increased it by another 70%. Neither of the two
      peptides effected bile acid output. Both VIP and secretin increased bicarbonate
      output, whereas only VIP increased the concentration. The clearance of [14C]
      erythritol was uneffected by VIP infusion, but increased following secretin, as
      did the clearance of [14C]-mannitol. Thus, VIP stimulated bile secretion at the
      ductular level, whereas secretin seemed to stimulate bile secretion both at the
      ductular level and at the bile acid non-dependent canalicular level (Paper III).
      4. Whereas VIP stimulated bile secretion, somatostatin decreased it by some 40%.
      Even when somatostatin was administered during VIP infusion, no reduction of the
      VIP-induced choleresis was seen. VIP increased both bicarbonate concentration and
      output, whereas somatostatin had the opposite effect. The concentration of
      chloride increased following VIP infusion, but decreased following somatostatin.
      The output of bile acids was not influenced by VIP infusion and decreased by
      somatostatin, whereas total lipid concentration increased during somatostatin
      infusion with a decrease when VIP was added. Thus, somatostatin acts on the bile
      acid-dependent canalicular bile secretion and also, to some extent, on the
      ductular secretion. The effects of the two peptides on bile secretion are
      independent of each other (Paper IV). 5. While fasting, 6-8 days after bile duct
      surgery, bile secretion averaged 290 microliters/min. Canalicular bile secretion,
      as measured by the clearance of [14C]-erythritol, constituted some 80% of total
      bile flow. Maximum de novo synthesis of bile acids was 8.7 mmol/24 h, implying a
      8-9 fold stimulation due to interrupted enterohepatic circulation (Paper V). 6.
      No serious side effects from this method with temporary bile fistulas following
      bile duct surgery were found. Therefore, the method is recommended for further
      research on human bile secretion (Paper V).

PMID- 1981636
TI  - Syme's amputation.
AB  - Syme's amputation was performed in one stage in 8 and in two stages in 13
      patients. Failures were defined as those requiring a more proximal amputation and
      were present in patients with vascular disease only. The failure rate was 38% in
      the group with vascular disease and 24% in the total group. Syme's amputation
      provides the patient with a durable end-bearing stump, even in insensitive feet.

PMID- 1981638
TI  - Excitatory amino acids and neuronal plasticity. Proceedings of the European
      Neuroscience Association satellite symposium on excitatory amino acids and
      neuronal plasticity. August 27-31, 1989, Fillerval, France.

PMID- 1981637
TI  - [Open clinical study of the efficacy and safety of Halazepam in anxiety
      disorders].
AB  - Two open clinical studies were done to evaluate the therapeutic effectiveness and
      safety of Halazepam. These studies were carried out on an overall sampling of 81
      somatic patients suffering from adaptive disorders and symptoms of anxiety,
      according to DSMIII criteria. The sampling was made up of 40 patients referred
      for general psychiatric consultation in the Ramon y Cajal Hospital (from any
      other medical or surgical department) and 41 cardiologic patients (both in- and
      out-patients). The mean age of the patients referred for general consultation was
      40.0, and the mean age of the cardiologic patients was 55.5 years. The posologic
      standard was 20-120 mg/day, in a single dose or divided into several doses. The
      following clinical evaluation criteria were applied: Hamilton Anxiety Scale (HS),
      Physician Evaluation of Improvement (PhEI) and Patient Evaluation of Improvement
      (PaEI). To determine the safety of the medication, a modified Dotes Secondary
      Effects Scale was used. At the beginning of the study all the patients had scores
      of less than or equal to 18 on the Hamilton Depression Scale (HDS) and greater
      than or equal to 14 on the Hamilton Anxiety Scale. From the first week on till
      the end of treatment, a statistically significant improvement was observed, based
      on the scores of the different evaluation scales. Halazepam was found to improve
      the anxiety condition in 95.0% of the cardiologic patients and 92.5% of the
      general consultation group. All of the cardiologic patients and 87.5% of the
      general consultation ones completed the minimum study period (4 weeks)
      satisfactorily. The only undesirable effects observed were minor and short-lived,
      and it was not necessary to discontinue treatment in any of the cases. No changes
      were observed in the clinical significance of the analytic parameters monitored.
      The results of this study indicate that Halazepam is a fast, safe, effective and
      easy-to-use drug for treating anxiety.

PMID- 1981639
TI  - Protection by natural and semisynthetic gangliosides from Ca2(+)-dependent
      neurotoxicity caused by excitatory amino acid (EAA) neurotransmitters.

PMID- 1981640
TI  - Periodic inward currents triggered by NMDA in immature CA3 hippocampal neurones.

PMID- 1981641
TI  - A role of NMDA receptors and Ca2+ influx in synaptic plasticity in the developing
      visual cortex.

PMID- 1981643
TI  - Mechanisms of excitatory amino acid-induced stimulation of GABAergic synaptic
      activity in cultures from the rat superior colliculus.

PMID- 1981642
TI  - Spontaneous and evoked NMDA-receptor mediated potentials in the entorhinal cortex
      of the neonate rat in vitro.

PMID- 1981644
TI  - The role of taurine and glutamate during early postnatal cerebellar development
      of normal and weaver mutant mice.

PMID- 1981645
TI  - Regulation of neurite outgrowth from cerebellar granule cells in culture: NMDA
      receptors and protein kinase C.

PMID- 1981646
TI  - Long-term potentiation in the dentate gyrus in vivo is associated with a
      sustained increase in extracellular glutamate.

PMID- 1981647
TI  - Long-term potentiation is not associated with a sustained enhanced release of
      glutamate in the rat hippocampus in vivo and in vitro.

PMID- 1981649
TI  - Delayed onset of potentiation in neocortical EPSPS during long-term potentiation
      (LTP)--a postsynaptic mechanism or heterogeneous synaptic inputs?
AB  - Long-term potentiation (LTP) is an activity-dependent, long-lasting change in the
      efficacy of synaptic transmission, which is a possible neural substrate for
      learning and memory. We have induced LTP at some synapses in slices of rat
      sensorimotor cortex in vitro, by using either brief tetanic stimulation of
      afferent axons or an associative, postsynaptic method of induction. We were
      successful in inducing LTP of excitatory postsynaptic potentials (EPSPs) in 11
      out of 53 neurones in layers III, V or VI. In view of the importance of N-methyl
      D-aspartate (NMDA) receptor activation for the induction of LTP in neocortex, as
      in regions of hippocampus, we hypothesized that the failures of induction of LTP
      might be due to a lack of NMDA-receptor mediated activity in the afferent pathway
      onto layer V and VI neurones. Hence we bath-applied the selective NMDA-receptor
      antagonist 2-amino-5-phosphonopentanoic acid (AP5) and examined its effect on
      composite PSPs evoked in layer V and VI neurones. We found that 94% of PSPs
      (44/47) were partly mediated by NMDA-receptor activity, so a lack of functioning
      NMDA receptors was not likely to be the reason for failures of induction of LTP
      by afferent tetanic stimulation. When we induced LTP (in the absence of AP5) and
      applied AP5 15 to 20 min after the establishment of LTP, the expression of LTP
      was reversibly reduced: during LTP, synaptic responses consisted of an early AP5
      insensitive component and a later AP5-sensitive component. This was seen in both
      EPSPs and field potentials in layers V and VI. Although the depolarising slope of
      most of the neocortical EPSPs was increased during the expression of LTP, we
      found that in 9/11 short latency EPSPs the onset of the potentiated component of
      the EPSP was delayed by a few ms with respect to the onset of the EPSP. In 7 of
      the 9 EPSPs the LTP was induced postsynaptically by pairing an evoked EPSP
      repetitively with intracellular depolarising pulses. The explanation for the
      delayed onset of the potentiated component in these EPSPs could be either that a
      postsynaptic voltage-sensitive mechanism was involved, or that the afferent
      terminals on the neurons were heterogeneous. The afferents responsible for the
      shortest latency components of the neocortical EPSPs may not be capable of
      sustaining LTP.

PMID- 1981648
TI  - Glutamate receptors in cultures of mouse hippocampus studied with fast
      applications of agonists, modulators and drugs.

PMID- 1981650
TI  - Local circuit connections mediated by NMDA and non-NMDA receptors in slices of
      neocortex.

PMID- 1981651
TI  - The role of protein kinase C substrate B-50 (GAP-43) in neurotransmitter release
      and long-term potentiation.

PMID- 1981652
TI  - Different mechanisms and multiple stages of LTP.

PMID- 1981653
TI  - Homocysteic acid as transmitter candidate in the mammalian brain and excitatory
      amino acids in epilepsy.

PMID- 1981654
TI  - Intracellular messengers associated with excitatory amino acid (EAA) receptors.

PMID- 1981655
TI  - [Clinical evaluation of urinary glycyl-prolyl dipeptidyl aminopeptidase in
      patients with urological disease].
AB  - Urinary glycyl-prolyl dipeptidyl aminopeptidase (GP-DAP) activity was measured in
      18 healthy adults and 252 patients with urological diseases. The GP-DAP activity
      was significantly higher in patients with prostatic cancer, bladder cancer or
      renal cancer and also in patients with acute prostatitis or pyelonephritis than
      in healthy adults. GP-DAP activity was also studied during anticancerous
      chemotherapy and proved to be a sensitive parameter for renal damage as are
      urinary N-acetyl-beta-D-glucosaminidase, alanine aminopeptidase, beta 2
      microglobulin, alpha 1-microglobulin, and albumin. The analysis of tissue
      activities suggested that GP-DAP was located not only in the renal parenchyma but
      also in the prostate and seminal vesicles.

PMID- 1981656
TI  - [Morphofunctional characteristics of the heart mitochondria during adrenergic
      stimulation and blockade under ketamine anesthesia].
AB  - A reduction of breathing control in palmitoylcarnitine oxidation without changes
      in phosphorylation efficacy coefficient have been noted upon intraabdominal
      injections of ketamine to rats at a dose of 50 mg/kg. The morphological signs
      noted were: mitochondrial matrix induration and insignificant focal disturbances
      of cardiac apparatus (myofibril) contractility. In beta-adrenergic stimulation of
      the heart by novodrine during ketamine anesthesia a sharp reduction in breathing
      control and phosphorylation efficacy coefficient are observed with the oxidation
      of succinate, caprylic acids and palmitoylcarnitine by myocardial mitochondria.
      Morphologically the disturbance of mitochondrial cysts, appearance of
      mitochondrial myelinic structures and partial destruction of mitochondrial
      membranes have been observed. In beta-adrenergic heart blockade by adrenoblockers
      obsidan and cordanum during ketamine anesthesia, obsidan induces an increase in
      phosphorylation efficacy coefficient, with morphologically normal energy and
      contractility apparatus. Cordanum is not so effective when used during ketamine
      anesthesia.

PMID- 1981657
TI  - The Development and Neural Bases of Higher Cognitive Functions. A conference. May
      20-24, 1989, Philadelphia, Pa.

PMID- 1981658
TI  - Enzyme Engineering 10. Tenth International Enzyme Engineering Conference,
      Kashikojima, Japan, September 24-29, 1989. Proceedings.

PMID- 1981660
TI  - Gamma-glutamyl-transpeptidase.

PMID- 1981659
TI  - Therapeutic effect of hepatocytes entrapped within Ca-alginate.

PMID- 1981661
TI  - Syntheses of gamma-glutamyl peptides by gamma-glutamyltranspeptidase from E.
      coli.

PMID- 1981662
TI  - Genetic profile of cosmopolitan populations: effects of hidden subdivision.
AB  - Natural populations of many organisms exhibit excess of rare alleles in
      comparison with the predictions of the neutral mutation hypothesis. It has been
      shown before that either a population bottleneck or the presence of slightly
      deleterious mutations can explain this phenomenon. A third explanation is
      presented in this work, showing that hidden subdivision within a population can
      also lead to an excess of rare alleles in the total population when the
      expectations of the neutral model are based on the allele frequency profile of
      the entire population data. With two examples (mitochondrial DNA-morph
      distribution and isozyme allele frequency distributions), it is shown that most
      cosmopolitan human populations exhibit excess of rare as well as total allele
      counts, when these are compared with the expectations of the neutral mutation
      hypothesis. The mitochondrial data demonstrate that such excesses can be detected
      from genetic variation at a single locus as well, and this is not due to
      stochastic error of allele frequency distributions. Contrast of the present
      observations with the allele frequency profiles in agglomerated tribal
      populations from South and Central America shows that even when the neutral
      expectations hold for individual subpopulations, if all subpopulations are
      grouped into a single population, the pooled data exhibit an excess of total
      number of alleles that is mainly due to the excess of rare alleles. Therefore, a
      primary cause of the excess number of rare alleles could be the hidden
      subdivision, and the magnitude of the excess indicates the extent of
      substructuring. The two components of hidden subdivision are: 1) Number of
      subpopulations, and 2) the average genetic distance among them. The implications
      of this observation in estimating mutation rate are discussed indicating the
      difficulties of comparing mutation rates from different population surveys.

PMID- 1981663
TI  - The chemotherapy of rodent malaria. XLV. Reversal of chloroquine resistance in
      rodent and human Plasmodium by antihistaminic agents.
AB  - The inherent blood schizontocidal activities of five antihistaminic compounds,
      cyproheptadine hydrochloride (CYP), ketotifen hydrogen fumarate (KET), pizotyline
      hydrogen maleate (PIZ), azatadine maleate (AZAT) and loratadine (LOR) were
      examined against the following organisms: chloroquine-sensitive (CS) Plasmodium
      berghei and chloroquine-resistant (CR) P. yoelii ssp. NS in mice; and CS Tak 9
      clone 96 and CR K1 strain of P. falciparum in vitro. Chloroquine, verapamil and
      desipramine were used as comparison standards. CYP, KET, PIZ were active against
      the CS strain in vivo with ED90 levels between 20 and 30 mg kg-1 (given sc daily
      for four days). They were slightly more active against the CR strain. AZA was
      active, but much less so than the other compounds. LOR, verapamil and desipramine
      were inactive in vivo at the doses tested. Against CS P. falciparum in vitro, all
      five antihistaminics and desipramine were active at EC50 concentrations ranging
      from about 50-80 mumol l-1, while verapamil was only active at 175 mumol l-1.
      Against the CR strain of this parasite, CYP, PIZ and LOR were slightly more
      active than against the CS strain, but KET, AZAT, desipramine and verapamil were
      significantly less active. The action of all these compounds in combination with
      chloroquine was then examined both in vivo and in vitro. The ability of verapamil
      and desipramine to reverse chloroquine resistance in vitro was confirmed, but
      only a low level of reversal was seen with these compounds in vivo. However, CYP,
      KET, PIZ and AZAT produced a marked reversal of chloroquine resistance both in
      vivo and in vitro. The implications of these observations in relation to further
      laboratory and clinical research are discussed.

PMID- 1981664
TI  - Dopamine agonist activity of 8-OH-DPAT.
AB  - We have investigated the effects of 8-OH-DPAT in the mouse isolated vas deferens
      preparation and found it to possess a biphasic (initial inhibition followed by
      potentiation) dose-response curve. The initial inhibitory phase of the dose
      response curve was not antagonized by naltrexone (300 nM), idazoxan (300 nM) or
      propranolol (300 nM), indicating that neither opioid, alpha 2- nor beta-receptors
      were involved in the inhibition. (+/-)-Cyanopindolol (300 nM) was also devoid of
      any antagonist activity versus 8-OH-DPAT, showing that the effect of the compound
      is not due to 5-HT1A or 5-HT1B agonist activity. Domperidone (10 nM),
      fluphenthixol (30 nM) and sulpiride, three chemically dissimilar DA2 antagonists,
      all antagonized the effects of DPAT, indicating that the compound is acting as a
      dopamine agonist in this preparation. A comparison, in the same preparations, of
      the agonist effects of DPAT and apomorphine, showed that DPAT possesses ca 0.01
      the potency of apomorphine. The dose-response curve produced by DPAT was much
      shallower than that produced by apomorphine, indicating that DPAT is only a
      partial agonist in this preparation. This was confirmed by subsequent experiments
      which showed that DPAT, at a concentration of 3 microM, which had no effect on
      dose-response curves to the opioid agonist normorphine, produced a ca 10-fold
      shift in the dose-response curve to dopamine.

PMID- 1981665
TI  - Evidence that 5-HT2 receptors mediate the pressor effect of 8-OH-DPAT in the
      spinally pithed rat.
AB  - The aim of the present experiments was to investigate whether 8-OH-DPAT, a
      selective 5-HT1A agonist, could induce vasoconstriction in vivo and, if so, the
      type of receptors functionally involved. Dose-response curves to bolus
      intravenous doses of 8-OH-DPAT were established in anesthetized spinally pithed
      rats. The peak increase in the mean arterial pressure-log dose (microgram/kg)
      relationship was fitted to a sigmoidal logistic equation. In the control group,
      the dose-response curve was steep. The half maximal dose was 743 micrograms/kg.
      The maximal response was 43 mmHg. Ketanserin, a potent 5-HT2 and alpha 1
      adrenoceptor antagonist (0.25 mg/kg), essentially abolished the effect of 8-OH
      DPAT (maximal rise = 6 mmHg). Ritanserin (0.25 mg/kg) and LY 53857 (100
      micrograms/kg), which have relatively weak affinity for alpha 1-adrenoceptors,
      also markedly reduced the pressor action of 8-OH-DPAT (maximal rise 17 and 9
      mmHg). Prazosin, an alpha 1-adrenoceptor antagonist, slightly reduced the maximal
      response to 8-OH-DPAT (22% reduction). Adrenalectomy did not affect the pressor
      response (42 mmHg). This excluded a contribution of an acute release of
      adrenaline in the blood pressure elevation. (-)Propranolol (5 mg/kg), a beta
      blocker with a 5-HT1A antagonistic action, affected the 8-OH-DPAT-induced blood
      pressure elevation (37% reduction). However, two other beta-blockers with a
      similar 5-HT1A antagonistic property, (-)pindolol (5 mg/kg) and (+/
      )cyanopindolol (10 mg/kg), did not (maximal rise 44 and 39 mmHg). Finally, 8-OH
      DPAT dose-dependently increased local vascular resistances, with a regional
      profile similar to that of 5-HT, with the hindquarter being the most sensitive
      vascular bed. Ketanserin also prevented the vascular effects of 8-OH-DPAT. Our
      pharmacological analyses of the vascular action of 8-OH-DPAT in the spinally
      pithed rat indicated that this drug caused dose-related increases in blood
      pressure. This effect depended on a rise in peripheral vascular resistance,
      particularly in the hindquarter and kidney beds. Our data suggest that the 5-HT1A
      agonistic property of 8-OH-DPAT cannot account for this pressor effect which
      seems to depend on the activation of the vascular 5-HT2 receptor.

PMID- 1981666
TI  - Memory deficits following internal capsule lesions in rats and their improvement
      by L-6-ketopiperidine-2-carbonyl-L-leucyl-L-proline amide (RGH-2202), a
      thyrotropin-releasing hormone analogue.
AB  - A memory deficit model has been developed following bilateral internal capsule
      lesions in rats. During 12-49 days after internal capsule lesions, the rats
      showed a marked impairment of active avoidance acquisition in a step-through
      apparatus, while they exhibited no observable change in native behaviors, except
      a slight increase in exploratory activity. A passive avoidance task in the same
      apparatus was also impaired in internal capsule lesioned rats when examined after
      one-trial training, though the task was gradually acquired by repeated trainings.
      Moreover, the retention of both the active and passive avoidance responses in
      well-trained rats deteriorated after internal capsule lesions. On the other hand,
      internal capsule-lesioned rats did not perform any worse than sham-operated rats
      in a T-maze spontaneous alternation behavior and in a habituation response to a
      novel environment. In the frontal cortex and striatum of internal capsule
      lesioned rats, there was a significant decrease of dopamine, serotonin and their
      metabolites, but no change of acetylcholine levels. The acquisition deficit of
      active avoidance in internal capsule-lesioned rats was improved by thyrotropin
      releasing hormone (TRH, 10 mg/kg, i.p.) and L-6-ketopiperidine-2-carbonyl-L
      leucyl-L-proline amide (RGH-2202, 10 mg/kg, i.p., 0.2 and 1 mg/kg i.v.), but not
      by physostigmine sulfate (0.2 mg/kg, i.p.). These results indicate that bilateral
      internal capsule lesions in rats induce long-term memory deficits which are
      paralleled with a decrease of the contents of monoamines and their metabolites
      and improved by TRH and RGH-2202.

PMID- 1981667
TI  - Comparison between ketanserin and LY 53857 on vascular and cardiac 5-HT2 and
      alpha 1-adrenergic receptors in the pithed rat.
AB  - In normotensive pithed rats, both ketanserin and LY 53857 potently antagonized
      the increase in blood pressure induced by 5-HT in a noncompetitive manner.
      However, LY 53857 differs from ketanserin in that it shifts the pressor dose
      response curve to 5-HT in a parallel way at low doses but in a noncompetitive way
      at higher doses. Ketanserin and LY 53857 were weak antagonists of the pressor
      effects of phenylephrine. LY 53857 was more potent and more selective than
      ketanserin for 5-HT2 vs alpha 1-adrenergic receptors.

PMID- 1981668
TI  - Alpha 2-adrenoceptor-blocking properties of midaglizole (DG-5128) in rats.
AB  - The alpha 2-adrenoceptor antagonistic potency of midaglizole was evaluated and
      compared with that of the selective alpha 2-adrenoceptor antagonists yohimbine
      and idazoxan. Intravenously administered midaglizole, like yohimbine and
      idazoxan, reversed the clonidine-induced inhibition of the tachycardic response
      to cardiac nerve stimulation in pithed rats. Midaglizole, yohimbine and idazoxan
      inhibited the pressor responses to B-HT 920 (alpha 2-adrenoceptor agonist), in a
      dose-related manner, to a greater extent than the response to methoxamine (alpha
      1-adrenoceptor agonist). Conversely, prazosin produced a highly selective
      antagonism of the methoxamine-evoked response in this preparation. Midaglizole
      failed to antagonize centrally mediated hypotension and bradycardia induced by
      intravenous clonidine, whereas the other alpha 2-antagonists attenuated the
      clonidine-induced cardiovascular responses in intact rats. These results suggest
      that midaglizole is a selective alpha 2-adrenoceptor antagonist and, unlike
      yohimbine and idazoxan, is characterized by its ability to block peripheral but
      not central alpha 2-adrenoreceptors when administered systemically.

PMID- 1981669
TI  - Effect of carnosine on the activation of human platelet soluble guanylate cyclase
      by sodium nitroprusside and protoporphyrin IX.
AB  - Effect of carnosine on the activation of soluble guanylate cyclase by sodium
      nitroprusside and protoporphyrin IX was studied using human platelet 105000 g
      supernatants and partially purified heme-deficient guanylate cyclase
      preparations. In experiments with 105000 g supernatants, carnosine (1 mM)
      inhibited the enzyme activation by nitroprusside by about 70%. With the partially
      purified heme-deficient guanylate cyclase, the enzyme activation by nitroprusside
      was lowered by 86%, and the remaining insignificant stimulatory effect remained
      unchanged upon carnosine addition. The stimulatory effect of protoporphyrin IX on
      the partially purified heme-deficient enzyme preparation did not differ from that
      observed with the 105000 g supernatant; carnosine addition had no effect on
      activation of guanylate cyclase by protoporphyrin IX. It was concluded that the
      inhibitory effect of carnosine on the ability of the enzyme to be activated by
      nitroprusside is due to the interaction of carnosine with guanylate cyclase, and
      that it is heme directed.

PMID- 1981670
TI  - Mineralocorticoids modify rat liver delta 6 desaturase activity and other
      parameters of lipid metabolism.
AB  - The changes in linoleyl-CoA desaturase activity of rat liver microsomes were
      studied after a single intraperitoneal injection of 11-deoxycorticosterone or
      aldosterone at physiological doses. Fatty acid of plasma and different liver
      fractions, and physical properties of microsomal membranes were also
      investigated. It was found that the specific activity of delta 6 desaturase
      decreased 4-fold 24 hr after the injection of aldosterone or deoxycorticosterone.
      Pretreatment of the rats with aldosterone led to a significant decrease in the
      percent distribution of palmitic, arachidonic, docosapentaenoic and
      docosahexenoic acids, with a concomitant increase in palmitoleic, oleic and
      linoleic acids in plasma and liver homogenates, microsomes and cytosol fractions.
      A similar pattern was observed after deoxycorticosterone administration. The
      changes resulted in a decreased unsaturation index of all fractions studied and
      were well-correlated with the increase observed in fluorescence depolarization of
      the hydrophobic probe 1,6-diphenylhexatriene in liver microsomal membranes. The
      interlipid and lipid/protein ratios in microsomes remained constant after
      hormonal treatment. These results are consistent with the idea that the
      inhibition of delta 6 desaturase activity and the alterations in fatty acid
      composition induced by mineralocorticoids, are solely responsible for the
      measured decrease in liver microsomal membrane fluidity.

PMID- 1981671
TI  - Influence of diet and obesity on placental amino acid enzyme activities in the
      rat.
AB  - The objective of this study was to assess the impact of dietary obesity and acute
      starvation on the activity of placental enzymes involved in amino acid
      metabolism. Twenty-four hours starvation caused a significant fall (10%) in the
      foetal weight in rats fed standard diet, and this was associated with only modest
      changes in amino acid enzyme activities. In contrast, in obese rats, foetal
      weight was unaffected by acute starvation, and was accompanied by a reduced
      adenylate deaminase activity (24%) and lower ammonia concentrations (50%) in
      placentae of obese rats after 24h starvation. Thus obesity may confer a
      protective effect on the foetus growth during acute starvation of diminishing
      amino acid utilization.

PMID- 1981673
TI  - Phosphorylation by protein kinase C modulates agonist binding to striatal
      dopamine D2 receptors.
AB  - The effect of purified protein kinase C (PKC) on dopamine D2 receptor binding was
      studied. Saturation binding with [3H]spiperone was not affected. In competition
      experiments using agonists PKC-treated membranes showed a significant reduction
      in the proportion of high affinity sites, and the influence of GTP gamma S was
      abolished. These results suggest that PKC-dependent mechanisms can regulate the
      coupling between the dopamine D2 receptor and its G-protein.

PMID- 1981672
TI  - Relaxed specificity of endoproteinase Asp-N: this enzyme cleaves at peptide bonds
      N-terminal to glutamate as well as aspartate and cysteic acid residues.
AB  - Asp-N, an endoproteinase specific for cleavage of protein or polypeptide bonds N
      terminal to aspartate or cysteic acid residues, has been shown to possess a
      similar affinity for certain glutamate residues. Of 18 glutamate residues present
      in 2 cyanogen bromide fragments of apolipoprotein A-I, 5 residues were cleaved at
      rates comparable to that of cleavage at the 12 internal aspartate residues
      present in these polypeptides (all of which were cleaved). Cleavage of these 5
      glutamate residues was obtained under standard enzyme digestion conditions, and
      the identities of all peptides obtained by Asp-N digestion were determined by
      amino acid sequencing of peaks obtained from reversed-phase high performance
      liquid chromatography.

PMID- 1981674
TI  - Tracheobronchial and nasal circulation. A symposium. 7-8 July 1989, Porvoo,
      Finland.

PMID- 1981676
TI  - Effects of neurotransmitters on tracheobronchial blood flow.
AB  - Blood flow in the tracheobronchial airways is regulated by three main nervous
      pathways: 1) sympathetic motor nerves (adrenergic and nonadrenergic); 2)
      parasympathetic motor nerves (cholinergic and noncholinergic); and 3) afferent or
      sensory nerves (peptidergic). Noradrenaline is the main adrenergic mediator which
      produces short-lasting constrictions in both tracheal and bronchial vascular beds
      and in both arteries and veins. These responses are mediated via alpha
      adrenoceptors. The nonadrenergic mediator neuropeptide Y is a vasoconstrictor
      which produces long-lasting responses with larger doses. Acetylcholine is the
      principal mediator of the cholinergic nerves and causes short-lasting dilations
      at all levels of the tracheobronchial circulation (arteries, veins and
      bronchopulmonary anastomoses). These responses are mediated via muscarinic
      receptors. Vasoactive intestinal peptide (VIP) and peptide histidine isoleucine
      (in man peptide histidine methionine) are the main mediators of the
      noncholinergic nerves. Both of them produce vasodilation in the tracheobronchial
      circulation; VIP can cause longer-lasting responses with larger doses. The
      afferent or sensory nerves contain tachykinins, i.e. substance P and neurokinins
      A and B, which are potent vasodilators in the tracheobronchial circulation and
      also potent inducers of postcapillary permeability. Calcitonin gene-related
      peptide is another sensory neuropeptide with ability to produce long-lasting
      vasodilations without affecting microvascular permeability.

PMID- 1981675
TI  - Airway mucosal blood flow: response to autonomic and inflammatory stimuli.
AB  - A major portion of airway blood flow is distributed to the subepithelial tissue
      space and is strategically located to influence both epithelial and airway smooth
      muscle functions. To assess the magnitude and responsiveness of blood flow
      through the subepithelial microvasculature, we measured tracheal mucosal blood
      flow with a soluble gas method in intact sheep. We found responses of tracheal
      mucosal blood flow to pharmacological stimuli alpha- and beta- (adrenoceptor
      agonists) and inflammatory stimuli (antigen and histamine), and demonstrated that
      alterations in mucosal blood flow influence the magnitude and duration of
      allergic airway smooth muscle contraction in the trachea. Mucosal blood flow,
      which under certain circumstances is regulated independently of total airway
      blood flow, could play a critical role in the manifestations of and recovery from
      airway disease.

PMID- 1981677
TI  - Effects of treatment on airway microvascular leakage.
AB  - Microvascular leakage, an essential component of inflammation, probably plays a
      critical role in asthma in producing plasma exudation and thickening of the
      bronchial mucosa which may underlie airway hyperresponsiveness. Several
      therapeutic approaches are possible to reduce this leakage, by blocking either
      the effects or the release of inflammatory mediators which induce the leakage.
      Drugs with these actions might be too specific to be of therapeutic value if many
      mediators are involved, as seems increasingly likely. Reduction of blood flow
      using selective vasoconstrictors is a more attractive approach and alpha 1
      adrenoceptor agonists may be of value. Drugs that act directly on endothelial
      cells are probably the most useful, since they would be effective irrespective of
      the mechanism of leakage. Corticosteroids probably have this property, but
      whether beta-agonists or theophylline are clinically effective against airway
      microvascular leakage is not yet certain. The development of new drugs which can
      inhibit microvascular leakage is an important therapeutic approach for the
      future.

PMID- 1981678
TI  - Synthesis and biological activity of 2-amino-1-oxa-2,3-dihydro-1-H-phenalene
      derivatives.
AB  - The preparation of two 2-dialkylamino-1-oxa-2,3-dihydro-1H-phenalenes (3 and 4)
      is described. Lewis acid-catalyzed Baeyer-Villiger reaction of acenaphthenone (5)
      gave the lactone 6. Reduction afforded the lactol 7, which was reacted with
      amines to give the target compounds 3 and 4. Investigation of the effects of
      these compounds on catechol and indole metabolism revealed that they lack the
      dopamine antagonist or agonist and serotonin agonist properties of the respective
      deoxy analogues.

PMID- 1981679
TI  - Effect of monoclonal antibodies on primate allograft rejection.

PMID- 1981680
TI  - [Molecule--hippocampus--memory. Part I: On the molecular mechanisms of synaptic
      plasticity].

PMID- 1981681
TI  - The efficacy and tolerability of long-term felodipine treatment in hypertension.
      The Scandinavian Multicenter Group.
AB  - The antihypertensive effect of felodipine and hydrochlorothiazide, both given in
      addition to beta-blockers, were compared in this double-blind multicenter study
      in 103 patients. To all patients concluding the study (n = 92), felodipine was
      given openly, and the antihypertensive effect and tolerability was studied for 1
      year. Patients with a diastolic blood pressure greater than or equal to 100 mmHg,
      despite beta-blocker treatment, were randomized to treatment with felodipine 5 mg
      twice daily (n = 51) or hydrochlorothiazide 25 mg (n = 52) once daily for 4
      weeks. The dose was then doubled in all patients for a second 4-week period.
      During open follow-up, all patients were given felodipine 5-15 mg (starting dose
      5 mg) twice daily in addition to the beta-blocker. Hydrochlorothiazide could also
      be added. Reductions in systolic and diastolic blood pressure were significantly
      greater with felodipine than with hydrochlorothiazide at both the low and high
      dose levels. There were significantly more responders (diastolic blood pressure
      less than or equal to 90 mmHg or fall of greater than or equal to 10 mmHg) in the
      felodipine group. Felodipine and hydrochlorothiazide were both well tolerated.
      Hydrochlorothiazide treatment was accompanied by a decrease in serum potassium
      and an increase in serum uric acid. One year of treatment felodipine therapy
      resulted in a blood pressure fall from baseline of 34/23 mmHg. The most commonly
      reported adverse event was ankle edema. No clinically important changes in blood
      tests were seen during felodipine treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1981682
TI  - Prevention of sudden death by beta-blockade.
AB  - Beta-adrenoreceptor blocking agents have been used to relieve symptoms mainly in
      patients with ischemic heart disease. Prophylactic use of beta blockade in
      patients after acute myocardial infarction has shown a reduction in total
      mortality and also in sudden death. The overall total mortality reduction amounts
      to about 30%, whereas the reduction in the sudden death rate is 50%. The
      mechanisms behind this reduction in sudden death are probably manifold.
      Antiarrhythmic effects in ischemic myocardium, prevention of new ischemia, and
      also perhaps other factors may play a role. Apart from the prevention effect in
      chronic ischemic heart disease, beta blockers have also been able to reduce the
      sudden death rate in the long QT syndrome and are suggested for use in congestive
      cardiomyopathy.

PMID- 1981683
TI  - Corneal refractive laser surgery: a critical appraisal of current lasers and
      methods. Saturday, September 15, 1990, Columbia University, New York, New York.

PMID- 1981684
TI  - [T cell receptor gamma delta expression of Thy-1+ dendritic epidermal cells--an
      update].
AB  - Thy-1+ dendritic epidermal cells (Thy-1+DEC) are present in the murine epidermis.
      They are morphologically dendritic and express Thy-1, CD3 and asialoGM1, but not
      CD4 or CD8. T cell receptor (TCR) of Thy-1+DEC is TCR gamma delta. Allison et al
      and Tonegawa et al recently found that TCR of Thy-1+DEC is V gamma 5 J gamma C
      gamma -V delta 1D2J2C delta and has no junctional diversity. This TCR gamma delta
      of Thy-1+DEC is identical to TCR expressed on the earliest fetal thymocytes. It
      is distinct from that of other epithelial associated lymphocytes or other
      thymocytes. The ligand of Thy-1+DEC is not known, although TCR gamma delta of
      adult type could recognize allogenic major histocompatibility complex(MHC) class
      I or class II and mycobacterium antigen, especially heat shock protein. The TCR
      of Thy-1+DEC may not be the homing receptor to epidermis. The further studies are
      needed to elucidate the ligands or functions of Thy-1+DEC.

PMID- 1981685
TI  - Alpha 2-adrenergic agonists stimulate DNA synthesis in Chinese hamster lung
      fibroblasts transfected with a human alpha 2-adrenergic receptor gene.
AB  - To test the hypothesis that agents activating receptors negatively coupled to
      adenylyl cyclase (AC) can stimulate cell proliferation, we have expressed a human
      alpha 2-adrenergic receptor (alpha 2-C10) in CCL39 cells and studied the effects
      of alpha 2-agonists on reinitiation of DNA synthesis in quiescent cells. We
      report that the alpha 2-agonists epinephrine and clonidine stimulate [3H]
      thymidine incorporation in synergy with fibroblast growth factor and that the
      alpha 2-antagonist yohimbine efficiently inhibits this response. Epinephrine- and
      clonidine-stimulated DNA synthesis is completely blocked by pertussis toxin and
      correlates well with the inhibition of prostaglandin E1-stimulated AC. Thus,
      their action closely resembles the action of serotonin in the same cell system,
      which is mediated through 5-HT1b receptors. In fact, serotonin- and epinephrine
      stimulated DNA synthesis reinitiation is not additive, suggesting that both
      agents act through a common pathway. Interestingly, alpha 2-agonists also induced
      a moderate release of inositol phosphates, indicating that alpha 2-adrenergic
      receptors can interact both with the AC and phospholipase C messenger system.
      Activation of phosphoinositide (PI) turnover by epinephrine leads to a
      significant stimulation of Na+/H+ exchange but is insufficient to trigger a
      mitogenic response in CCL39 cells, as will be discussed. We found no evidence for
      epinephrine-induced activation of Na+/H+ exchange by a mechanism independent of
      PI breakdown.Our data show that alpha 2-adrenergic receptors can play a role in
      the regulation of cell proliferation in an appropriate context; also, the data
      support the hypothesis that receptors negatively coupled to AC must be taken into
      account as mediators of growth factor action in fibroblasts, in particular when
      activated in parallel with receptor tyrosine kinases.

PMID- 1981686
TI  - Activation by serotonin of starfish eggs expressing the rat serotonin 1c
      receptor.
AB  - Starfish oocytes were injected with mRNA for the serotonin 1c receptor or with
      rat brain poly A+ mRNA, incubated to allow expression of the membrane protein,
      then matured to eggs by addition of 1-methyladenine. Applying serotonin to these
      eggs caused cortical granule exocytosis like that occurring at fertilization.
      Because the serotonin 1c receptor specifically activates a G-protein, these
      results provide support for the hypothesis that sperm activate eggs by way of a
      receptor-G-protein interaction. The starfish oocyte may be a generally useful
      system for expression of exogenous mRNA for membrane proteins.

PMID- 1981687
TI  - Activation of mu- and delta-opioid receptors present on the same nerve terminals
      depresses transmitter release in the mouse hypogastric ganglion.
AB  - 1. The inhibitory actions of mu- and delta-opioid receptor agonists on the
      strong, single fibre synaptic input to neurones contained in the mouse
      hypogastric ganglion have been examined. 2. The opioid agonists [D
      Ala2,NMePhe4,Gly-ol5]enkephalin (DAMGO, 10 nM-10 microM), morphine (10-30 [D
      Ser2,Leu5,Thr6]enkephalin (DSLET, 3 nM-1 microM), [D-Pen2,D-Pen5]enkephalin
      (DPDPE, 10 nM-10 microM), all depressed the single fibre, all-or-nothing,
      nicotinic, excitatory synaptic potential (e.p.s.p.) recorded in mouse hypogastric
      ganglion neurones. U50488H (0.3-1 microM) was without effect. 3. The effect of
      DSLET, but not that of DAMGO, was reversed by the delta-opioid receptor-selective
      antagonist, ICI 174864 (0.3 microM). Naloxone (0.3 microM) antagonized the effect
      of both DSLET and DAMGO. 4. The site of action of the mu- and delta-receptor
      agonists was on the presynaptic terminals, since at the concentrations which
      depressed the e.p.s.p. these drugs did not affect the resting membrane potential
      or input resistance of the postganglionic neurone body, nor did they depress the
      postganglionic, nicotinic response to exogenously applied acetylcholine. 5.
      Quantal analysis further confirmed the presynaptic site of action; mu- and delta
      opioid receptor agonists decreased the mean number of quanta released per
      stimulus but did not reduce the mean amplitude of the quantal unit. 6. It was
      concluded that mu- and delta-opioid receptors were located on the same
      presynaptic nerve terminals since, in the same neurones, mu- and delta-opioid
      receptor agonists depressed the same single fibre inputs. 7. The potassium
      channel blockers barium and quinine, at concentrations known to block
      opioidactivated somatic potassium conductances, reduced slightly but did not
      abolish the mu- and delta-opioid receptor-mediated inhibition of the e.p.s.p.

PMID- 1981688
TI  - Evidence for the existence of 'atypical' beta-adrenoceptors (beta 3
      adrenoceptors) mediating relaxation in the rat distal colon in vitro.
AB  - 1. Experiments were carried out to characterize the adrenoceptors mediating
      relaxant responses in the rat distal colon. Three agonists were used:
      noradrenaline, isoprenaline and the beta 3-adrenoceptor agonist BRL 37344.
      Phentolamine, propranolol and (+/- )-cyanopindolol were tested as antagonists.
      Tone in the rat distal colon was induced with KCl (30-40 mM) as a spasmogen, and
      relaxations of this KCl-induced tone produced by the agonists were measured. 2.
      Relaxant responses to noradrenaline that were obtained in the presence of
      propranolol (1 microM) were not antagonized by phentolamine (0.01 to 1 microM).
      Relaxant responses to isoprenaline that were obtained in the presence of
      phentolamine (1 microM) were antagonized in a concentration-dependent manner by
      propranolol (0.01 to 3 microM), although this antagonism was weak and non
      competitive. Relaxant responses to BRL 37344 that were obtained in the presence
      of phentolamine (1 microM) were only weakly antagonized by high (1 microM)
      concentrations of propranolol. 3. Tachyphylaxis to BRL 37344 was observed, a
      second concentration-response curve being shifted to the right by 15 fold.
      Exposure of the tissues to BRL 37344 (1 microM) between concentration-response
      curves also caused rightward shifts in the responses to noradrenaline (18 fold)
      and isoprenaline (19 fold) but not to papaverine. 4. In the presence of
      phentolamine (1 microM) and propranolol (1 microM), the rank order of potency of
      the agonists was: (-)-isoprenaline (1.0) greater than or equal to BRL 37344
      (0.93) greater than (-)-noradrenaline (0.3). 5. Responses to BRL 37344 in the
      presence of phentolamine (1 microM) and propranolol (1 microM) were antagonized
      by (+/-)-cyanopindolol (I microM), with an apparent pA2 value of 6.67. Responses
      to isoprenaline, under the same conditions, were antagonized in a competitive
      manner by (+/-)-cyanopindolol (0.1 to 10 microM), with the slope of the Schild
      plot close to unity and a pA2 value of 7.12. 6. The resistance of the relaxant
      responses to antagonism by phentolamine and propranolol, along with the
      relatively high potency of the beta 3-adrenoceptor agonist BRL 37344 and the
      antagonism of 'resistant' responses by (+/-)-cyanopindolol would suggest that
      'atypical' beta 6-adrenoceptors, similar to the beta 3-adrenoceptors of rat
      adipocytes and other tissues, exist in the rat distal colon.

PMID- 1981689
TI  - Two distinct alpha 1-adrenoceptor subtypes involved in noradrenaline contraction
      of the rabbit thoracic aorta.
AB  - 1. Recently, alpha 1-adrenoceptors in blood vessels have been classified into
      three subtypes (alpha 1H, alpha 1L and alpha 1N). We examined which subtype (or
      subtypes) is involved in the noradrenaline-induced contraction of rabbit thoracic
      aorta. 2. Noradrenaline produced a concentration-dependent contraction in the
      rabbit isolated thoracic aorta. Prazosin antagonized the contractions to
      noradrenaline, resulting in a rightward displacement of the concentration
      response curve. However, the shift was not proportional to the concentration of
      prazosin; Schild plots showed that the inhibition by prazosin was biphasic,
      implying that noradrenaline acted through two receptor populations. Two affinity
      constants (pKB values of 10.02 and 8.83) were determined for prazosin at these
      sites. 3. However, under continuous treatment with 1 nM prazosin, or in strips
      pretreated with chlorethylclonidine (CEC; an alpha 1H inactivating agent) to
      remove the contribution of one receptor population, prazosin showed a single pKB
      or pA2 value of approximately 8.3. 4. Yohimbine also produced biphasic antagonism
      of noradrenaline-induced contractions, resulting in two affinity constants (pKB =
      6.52 and 6.17). However, a monophasic Schild plot was obtained for yohimbine
      either in the presence of 1 nM prazosin (pA2 = 6.08) or in strips pretreated with
      CEC (pA2 = 6.03). 5. The Schild plot for HV723 (a selective alpha 1N-antagonist)
      yielded a monophasic slope (pKB = 8.47) and the inhibition was not affected by 1
      nM prazosin or CEC-pretreatment. 6. [3H]-prazosin bound to alpha 1-adrenoceptors
      of the aortic membrane preparations with two different affinities (pKD = 9.94 and
      8.37). The high but not the low affinity site was completely masked by 1 nM
      prazosin and inactivated by pretreatment with CEC. 7. These results strongly
      suggest that noradrenaline-induced contraction of the rabbit thoracic aorta is
      mediated through two distinct alpha l-adrenoceptor subtypes, designated alpha 1H
      and (alpha lL*

PMID- 1981691
TI  - Pediatric Neurosurgery in Europe--state of the art, 1989. First European
      Symposium. June 16-19, 1989, Gardone Riviera, Italy.

PMID- 1981690
TI  - Evidence that the agonist action of dynorphin A(1-8) in the guinea-pig myenteric
      plexus may be mediated partly through conversion to [Leu5]enkephalin.
AB  - 1. The agonist action of the opioid peptide dynorphin A(1-8) on the myenteric
      plexus-longitudinal muscle of the guinea-pig ileum has been characterized. 2. The
      endogenous opioid peptide dynorphin A(1-8) was rapidly degraded by slices of
      myenteric plexus-longitudinal muscle of the guinea-pig ileum. 3. A product of the
      degradation was the delta-receptor preferring [Leu5]enkephalin. Levels of
      [Leu5]enkephalin were markedly increased in the presence of the peptidase
      inhibitors bestatin, thiorphan and captopril. 4. In the myenteric plexus
      dynorphin A(1-8) acted as a kappa-receptor agonist. In the presence of bestatin,
      thiorphan and captopril a mu-receptor agonist effect was observed. This mu
      agonist action was lost in the presence of N-[1-(RS)-carboxy-2-phenylethyl]Ala
      Ala-Phe-p-aminobenzoate, an inhibitor of the endopeptidase enzyme EC 3.4.24.15.
      5. The results suggest that formation of [Leu5]enkephalin from dynorphin A(1-8)
      may be an important conversion process. The enzyme responsible may be the Zn2(+)
      metalloendopeptidase, EC 3.4.24.15.

PMID- 1981692
TI  - Distribution of two forms of somatostatin in the brain, anterior intestine, and
      pancreas of adult lampreys (Petromyzon marinus).
AB  - The distribution of two major immunoreactive forms of somatostatin, somatostatin
      14 and somatostatin-34, within the brain, pancreas and intestine of adult
      lampreys, Petromyzon marinus, was identified using antisera raised against these
      peptides. Immunostaining of the brain is similar in juveniles and upstream
      migrants, and somatostatin-14 is the major somatostatin form demonstrated. A few
      somatostatin-34-containing cells are localized within the olfactory bulbs,
      thalamus and hypothalamus, but cells immunoreactive to anti-somatostatin-34 in
      the hypothalamus and thalamus do not co-localize somatostatin-14. Immunostaining
      of pinealocytes within the pineal pellucida with anti-somatostatin-14 may infer a
      novel function for this structure. Somatostatin-14 and somatostatin-34 are co
      localized within D-cells of the cranial pancreas and caudal pancreas of juveniles
      and upstream migrants. Numerous somatostatin-34-immunoreactive cells are
      distributed within the epithelial mucosa of the anterior intestine but not all of
      these cells cross-react with anti-somatostatin-14. It appears that somatostatin
      34 is the major somatostatin in the pancreo-gastrointestinal system of adult
      lampreys.

PMID- 1981694
TI  - Gastrointestinal absorption of chlorothiazide: evaluation of a method using
      salicylazosulfapyridine and acetaminophen as the marker compounds for
      determination of the gastrointestinal transit time in the dog.
AB  - Gastrointestinal absorption properties of chlorothiazide was investigated in dogs
      by a double-marker method using acetaminophen and salicylazosulfapyridine as the
      markers. The mean absorption time of acetaminophen (MATAAP) and the time for
      first appearance of sulfapyridine in plasma (TFASP) were used for the assessment
      of gastric emptying and oro-colonic transit times, respectively. Chlorothiazide
      absorption efficiency was increased by pretreatment with atropine sulfate. There
      was a good correlation between MATAAP and the extent of bioavailability of
      chlorothiazide, however, there was no correlation between TFASP and the extent of
      bioavailability of the drug. These results indicate that chlorothiazide
      absorption takes place primarily in a limited segment of the upper small
      intestine, supporting the assumption reported previously. This double-marker
      method seems to be a useful tool for the investigation of the relationship
      between drug absorption and its gastrointestinal transit.

PMID- 1981693
TI  - Developmental expression of serotonin-like immunoreactivity in the
      sympathoadrenal system of the chicken.
AB  - The avian sympathoadrenal system has been used as a model to examine the
      differentiation of cells expressing neuroactive substances derived from the
      neural crest. Previous studies have dealt with the expression of the "classical"
      neurotransmitters acetylcholine and catecholamines and of the neuropeptides
      somatostatin and vasoactive intestinal polypeptide. We have used
      immunocytochemistry to examine the developmental expression of the monoamine
      serotonin (5HT) in the chicken sympathoadrenal system. 5HT-like immunoreactivity
      (5HT-LI) was found to be transiently expressed by cells of the sympathetic
      ganglia very early in development (E-5 to E-8), disappearing almost entirely at
      more advanced embryonic stages (E-10 to E-19) and post-hatched chickens where
      only a population of cells similar to mammalian small intensely fluorescent cells
      express immunoreactivity to the amine. In contrast, in the adrenal gland of
      embryos and post-hatched chickens, most chromaffin cells also express 5HT-LI.
      Double labeling experiments show that in both the adrenal gland and the
      sympathetic ganglia catecholaminergic properties and somatostatin
      immunoreactivity are co-expressed with 5-HT-LI. Moreover, the cells that
      transiently express 5HT-LI in sympathetic ganglia also transiently express
      somatostatin. The catecholaminergic cells expressing serotonin and somatostatin
      appear to define a biochemical phenotype common to some chromaffin cells, small
      intensely fluorescent cells and early sympathoblasts.

PMID- 1981695
TI  - [The analgesic treatment of the surgical patient].
AB  - An effective treatment of postoperative pain can achieve a better postop course
      especially in high risk patients. Pain is unacceptable when it can be relieved
      and, beside all it causes vasoconstriction, hypertension, tachycardia, fluid
      retention and pulmonary hypoventilation. A correct use of both narcotic drugs and
      NSAIDs are sufficient in most cases. In high risk patients, mainly after thoracic
      and upper abdominal procedures, insertion of a peridural catheter for drug
      administration can be very useful. The authors discuss the therapeutic
      possibilities according mainly to their experience.

PMID- 1981696
TI  - Diagnosis and management of panic disorder.

PMID- 1981697
TI  - Perspectives on bipolar illness.
AB  - Based on evidence available at present, it appears that heterogeneity does exist
      within bipolar disorder. Persons with mania differ in family history of affective
      illness, their age at the onset of illness, sex, and organic cause and course of
      the illness. The question of how these variables influence an individual's
      response to treatment has never been systematically studied. Multicenter trials
      of the various antimanic agents need to be conducted to determine whether the
      various subgroups of manic patients have different pharmacological response
      profiles. At present, the clinical management of mania is best approached using
      lithium carbonate in a dosage adequate to achieve a 12-hour serum lithium level
      to 1.0 to 1.2 mEq/L. The time to response is usually 2 to 3 weeks, and during
      this period an antipsychotic or benzodiazepine agent may be added to help control
      symptoms such as agitation or sleeplessness. Prophylactic maintenance with 12
      hour serum lithium levels between 0.8 and 1.0 mEq/L should be used for at least 6
      to 12 months after resolution of the manic episode. In patients with more than
      one episode, lithium maintenance therapy may need to be continued indefinitely.
      In patients who are not responsive to lithium, the most prominent alternative
      therapies include anticonvulsants and calcium-channel blocking agents.
      Anticonvulsants (e.g., carbamazepine, valproic acid, clonazepam) are generally
      first used as alternative therapy (either alone, or in combination with lithium),
      followed by a calcium-channel blocker (e.g., verapamil). Clinical practice would
      generally suggest first using the alternative agent alone, then adding lithium if
      response is inadequate.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1981698
TI  - Etizolam in the treatment of generalized anxiety disorder: a double-blind study
      versus placebo.
AB  - A double-blind, placebo-controlled study was carried out in 36 patients diagnosed
      as suffering from Generalized Anxiety Disorder with associated depressive
      symptoms to assess the efficacy and tolerability of two unitary doses of
      etizolam. After a 1-week wash-out period on placebo, patients were assigned at
      random to receive 1 tablet twice daily of either 0.50 mg or 0.25 mg etizolam or
      placebo for 5 weeks. Assessments were made at entry, on Day 21 and Day 35 of the
      patients' condition and symptoms using a battery of four psychometric tests (the
      Hamilton rating scales for anxiety and for depression, the Covi scale for anxiety
      and the Raskin scale for depression). Ten patients were withdrawn before the end
      of the study, 8 because of inadequate response (4 on placebo, 3 on 0.25 mg
      etizolam and 1 on 0.50 mg etizolam) in spite of dosage increase to 1 tablet 3
      times daily, and 2 because of side-effects (both on 0.50 mg etizolam). Analysis
      of the results from the remaining 26 patients showed that, at the 0.50 mg dosage
      level, etizolam produced significant improvement in anxiety and depressive
      symptoms, particularly somatic manifestations, and was significantly more
      effective than placebo or the 0.25 dosage regimen. Etizolam was generally well
      tolerated and the few side-effects reported, mainly daytime drowsiness, were of
      mild to moderate severity.

PMID- 1981699
TI  - [Peripheral blood T-cell subsets in patients with ovarian malignancies].
AB  - Blood samples from 79 subjects (27 cases of ovarian malignancy, 2 ovarian
      borderline epithelial tumor, 38 benign gynecologic disease and 12 healthy women)
      were measured for peripheral blood T-cell subsets using monoclonal antibodies and
      SPA-Ig rosette technique. It was found that in patients with ovarian malignancy,
      the percentage of OKT4+ cells was significantly reduced whereas the percentage of
      OKT8+ cells was markedly increased as compared with those in the healthy women
      and patients with benign gynecologic disease; OKT4/OKT8 ratio declined obviously;
      which were more pronounced in patients with advanced or recurrent tumor.

PMID- 1981700
TI  - Expressing the specificity and the potency of cytochrome P-450 inducers toward 7
      ethoxyresorufin.

PMID- 1981701
TI  - Bioavailability, metabolism, and renal excretion of benzoic acid in the channel
      catfish (Ictalurus punctatus).
AB  - The pharmacokinetics and metabolism of the model compound benzoic acid were
      examined after intravascular (iv) and po administration at 10 mg/kg in the
      channel catfish (Ictalurus punctatus). A two-compartment pharmacokinetic model
      best described the plasma disposition of parent benzoic acid after iv dosing. The
      following pharmacokinetic values were estimated: elimination half-life, 5.9 hr;
      total body clearance, 61 ml/hr/kg; and volume of distribution (steady-state), 369
      ml/kg. Plasma protein binding of [14C]benzoic acid was 18%. Benzoic acid was
      rapidly and extensively absorbed after po administration; absorption half-life
      was 0.8 hr and bioavailability was 95%. Renal excretion was the primary route of
      elimination of benzoic acid and metabolites. More than 80% of the iv-administered
      14C was recovered in the urine in 24 hr. Unchanged benzoic acid comprised more
      than 90% of the urinary radiolabel. The major urinary metabolite was
      benzoyltaurine, which comprised 6-7% of the excreted 14C. Channel catfish were
      qualitatively similar to other teleost fishes in the formation of the taurine
      conjugate of benzoic acid. In contrast, the primary mammalian metabolite is the
      glycine conjugate, hippuric acid.

PMID- 1981702
TI  - Isozymes of cytochrome P-450 that metabolize naphthalene in liver and lung of
      untreated mice.
AB  - Four isozymes, designated P-450m50a, P-450m50b, P-450m51a, and P-450m51b, have
      been isolated from liver microsomes of untreated male CD-1 mice.
      Electrophoretograms revealed that the molecular weights of P-450m51a and P
      450m51b were about 51,000, whereas those of P-450m50a and P-450m50b were about
      49,700 and 49,500, respectively. The present study is concerned mainly with the
      elucidation of the characteristics of P-450m50b and P-450m51a, since they appear
      to be major forms of cytochrome P-450 in mouse liver. End group analyses have
      revealed that these forms differ not only from P1-450, isolated previously from
      mouse liver, but also from any other known isozymes of cytochrome P-450.
      Naphthalene was metabolized by both P-450m50b and P-450m51a, but the turnover
      number of P-450m50b was 2-4 times greater than that of P-450m51a. Moreover, P
      450m50b formed predominantly (1R,2S)-naphthalene 1,2-oxide, as determined by the
      formation of trans-1(R)-hydroxy-2(R)-glutathionyl-1,2-dihydronaphthalene, whereas
      P-450m51a formed both (1R,2S)- and (1S,2R)-naphthalene 1,2-oxide in about equal
      amounts. Although cytochrome P-450c, isolated from rat liver, is also known to
      convert naphthalene predominantly to (1R,2S)-naphthalene 1,-2-oxide, an antibody
      prepared against cytochrome P-450c failed to inhibit the formation of the
      glutathione conjugate when the 1R,2S-oxide was formed by either pure P-450m50b or
      by microsomes from mouse lung. Thus, P-450m50b probably is not orthologous to
      cytochrome P-450c.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1981703
TI  - Effect of diabetes on disposition and renal handling of cefazolin in rats.
AB  - The effects of early-stage diabetes on disposition and renal handling of
      cefazolin (CEZ) were investigated in streptozotocin-induced diabetic rats.
      Significant increase in renal clearance was found in the diabetic rats (88%) and
      a strong correlation was obtained between renal and systemic clearance; however,
      there was no change in the volume of distribution. The results suggest that
      systemic clearance was increased as the result of enhancement of urinary
      excretion rate. Unbound fraction of CEZ in plasma was also increased by 60% in
      the diabetic rats and the increase may be due to the increase in glycosylated
      protein and plasma-free fatty acids. The filtration clearance for free drug in
      diabetic rats, which was estimated as glomerular filtration rate, was increased
      by about 1.9-fold compared to the normal rats, but the secretion clearance did
      not change in the two groups. Since kidney hypertrophy was observed in the
      diabetic rats, filtration and secretion clearance for free drug were normalized
      by means of kidney weight. After normalization for kidney weight, the two
      parameters were significantly reduced, indicating that the true kidney functions
      were impaired under the diabetic state. The parameters for CEZ secretion, maximum
      velocity and Michaelis-Menten constant, were also reduced in diabetic rats,
      suggesting that proximal tubule cell functions for secretion were altered in the
      diabetic rats. These results suggest that systemic and renal clearance was
      apparently increased in early-stage diabetes, whereas true kidney functions were
      impaired.

PMID- 1981704
TI  - Identification of urinary metabolites of cannabidiol in the dog.
AB  - Three dogs were treated with cannabidiol (CBD) and urine samples were collected
      periodically to 30 hr. Metabolites were extracted with ethyl acetate before and
      after hydrolysis with beta-glucuronidase, and examined by GC/MS,. Thirty-seven
      metabolites were identified and another nine partially characterized. Twenty-one
      of the identified metabolites have not been reported before for this drug. The
      major oxidative metabolic routes were 6-hydroxylation, both alpha and beta, and
      beta-oxidation. At 10 hr the major metabolites of this type were 6-hydroxy
      4'',5''-bis,nor-CBD-3''-oic acid and 6-oxo-4'',5''-bis,nor-CBD-3''-oic acid,
      whereas at 22 hr, further beta-oxidation had occurred to give 6-hydroxy
      2'',3'',4'',5''-tetrakis,nor-CBD-1"pr-oic acid as the major metabolite. Other
      metabolic routes were carboxylic acid formation at C-7 accompanied by
      hydroxylation in the side chain, and dihydroxylation of the C-8,9 double bond.
      Three compounds, 4''-hydroxy-CBD, 5''hydroxy-CBD, and 6-oxo-CBD were found at
      early times as glucose conjugates in concentrations that exceeded those of the
      other metabolites. The unconjugated forms of these metabolites were not found and
      none of the identified oxidized metabolites were found as glucosides. Only 4'',6
      dihydroxy-CBD was found conjugated with glucuronic acid.

PMID- 1981705
TI  - First-pass metabolism of gentisamide: influence of intestinal metabolism on
      hepatic formation of conjugates. Studies in the once-through vascularly perfused
      rat intestine-liver preparation.
AB  - Gentisamide (GAM) metabolism was studied in a once-through in situ perfused rat
      intestine-liver preparation in a manner which mimicked the first-pass effect. GAM
      (2.56 to 392 microM) was delivered into the intestine via the superior mesenteric
      artery at a flow of 7.5 ml/min. The intestinal venous outflow into the portal
      vein and the hepatic arterial flow (2.5 ml/min; without drug) served as dual
      inflows into the liver. The steady state intestinal extraction ratios (E1, 0.33
      to 0.06) and hepatic extraction ratios (EH, 0.84 to 0.37) were highly
      concentration dependent, decreasing with increasing GAM concentrations.
      Gentisamide-5-glucuronide was found to be the major intestinal metabolite, and
      gentisamide-2-sulfate was also formed, albeit to a much lesser extent. However,
      hepatic metabolism of GAM revealed 5-sulfation and glucuronidation as the
      predominant pathways, with GAM 2-sulfation as a minor pathway. About 1 to 3% and
      7% of dose was excreted into lumen and bile, respectively, mostly as GAM-5G. From
      the metabolic data, the fitted parameters confirmed that more enzymes exist in
      the liver than in intestine for the processing of GAM. The Km for 2-sulfation by
      the intestine was higher than the apparent Kms observed for 2- and 5-sulfation in
      liver. However, the Kms for 5-glucuronidation for both the intestine and liver
      were similar. The interrelationship between intestine and liver formation of
      first-pass metabolites showed that, at low GAM input concentration entering the
      IL preparation, the intestine, being the anterior organ, regulated the available
      substrate for hepatic elimination, and hence reduced the contribution of hepatic
      metabolism in the overall first-pass effect.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1981706
TI  - Estimations of intestinal and liver first-pass metabolism in vivo. Studies on
      gentisamide conjugation in the rat.
AB  - In this paper a method is introduced to study both intestinal and liver
      metabolism in the intact rat by cannulation of the jugular vein, carotid artery,
      pyloric vein (into the portal vein), and bladder. In this preparation, the rat
      received an initial dose followed by iv (I) and then intraportal (II) infusions.
      Gentisamide (2,5-dihydroxybenzamide, GAM) was used since it forms monosulfate
      (GAM-2S and GAM-5S) and monoglucuronide (GAM-5G) conjugates, metabolites that are
      not further metabolized. After administration of tracer amounts of radiolabeled
      gentisamide ([3H]GAM), the concentration ratio of [3H]GAM in the portal vein and
      carotid artery [CPV(I)/CA(I)] during iv infusion, and the ratio of carotid artery
      concentrations for intraportal to iv infusions [CA(II)/CA(I)] provided the
      intestine and liver availabilities, respectively; the corresponding extraction
      ratios for the intestine and liver were 0.26 to 0.27 and 0.37 to 0.41. Similar
      concentration ratios for the conjugates during iv administration [CPV(I)/CA(I)]
      showed intestine formation of GAM-5G, and to a lesser extent, GAM-2S, since the
      ratios exceeded unity; GAM-5S was not formed by the intestine since the ratio was
      unchanged. The ratio of the carotid arterial concentrations for intraportal to iv
      infusions that revealed hepatic formation showed similar values (1.77 and 1.71)
      for GAM-2S and GAM-5S, but variable (decreases and increases) GAM-5G values,
      whose mean value approximated unity. All findings were consistent with data
      obtained from the perfused rat liver preparation and the combined perfusion of
      rat intestine-liver preparation, where GAM-5G and GAM-2S were shown to be formed
      by the intestine, and where sulfation was the preferred pathway in the
      liver.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1981707
TI  - Cyclosporin A drug interactions. Screening for inducers and inhibitors of
      cytochrome P-450 (cyclosporin A oxidase) in primary cultures of human hepatocytes
      and in liver microsomes.
AB  - In previous papers we demonstrated that cyclosporin A (CsA) was specifically
      oxidized in rabbit and human liver by cytochrome P-450IIIA. We therefore
      anticipated that any drug that is an inducer or an inhibitor of this cytochrome
      should lead to interaction with CsA when given in association with it. In order
      to confirm this hypothesis, primary cultures of human hepatocytes and human liver
      microsomes were used to "reproduce" in vitro clinically significant interactions
      observed between CsA and drugs known either as specific inducers (i.e.,
      rifampicin) or as specific inhibitors (i.e., erythromycin) of P-450IIIA. Our
      results were in close agreement with the clinical reports. Human hepatocytes
      maintained in primary cultures for 72 hr in the presence of 50 microM rifampicin
      exhibited increased levels of P-450IIIA, determined by Western blot using
      specific antibodies, and concomitant increase in CsA oxidase activity, determined
      by HPLC analysis of extra and intracellular media. Conversely, these cultures
      exhibited erythromycin concentration-dependent decreases in CsA oxidase activity
      when incubated in the presence of 5, 20, and 100 microM erythromycin. In
      addition, a Lineweaver-Burk analysis of the erythromycin-mediated inhibition of
      CsA oxidase activity in human liver microsomes revealed competitive inhibition
      (with Ki of 75 microM) as expected, this macrolide being a specific substrate of
      P-450IIIA. Using this experimental approach, 59 molecules representative of 17
      different therapeutic classes were screened for inducers and inhibitors of CsA
      oxidase activity. Our results allowed us to elucidate the molecular mechanism of
      previously observed, but unexplained, drug interactions involving CsA, and to
      detect drugs that should interfere with CsA metabolism as inducers or inhibitors.
      Drugs detected as potential inducers of CsA oxidase included: rifampicin,
      sulfadimidine, phenobarbital, phenytoin, phenylbutazone, dexamethasone,
      sulfinpyrazone, and carbamazepine. Drugs detected as potential competitive
      inhibitors included: triacetyloleandomycin, erythromycin, josamycin, midecamycin,
      ketoconazole, miconazole, midazolam, nifedipin, diltiazem, verapamil,
      nicardipine, ergotamine, dihydroergotamine, glibenclamide, bromocriptine,
      ethynylestradiol, progesterone, cortisol, prednisone, prednisolone, and
      methylprednisolone. Finally, cefoperazone, cefotaxime, ceftazidime, isoniazide,
      doxycycline, spiramycin, sulfamethoxazole, norfloxacin, pefloxacin, vancocin,
      trimethoprim, amphotericin B, valproic acid, quinidine, cimetidine, ranitidine,
      omeprazole, diclofenac, aspirin, paracetamol, debrisoquine, guanoxan, captopril,
      furosemide, acetazolamide, sparteine, gliclazide, and imipramine were found not
      to interfere with the hepatic metabolism of CsA.

PMID- 1981708
TI  - In vitro metabolism of the novel antiinflammatory agent 6-(4'-fluorophenyl)-5-(4'
      pyridyl)-2,3-dihydroimidazo-[2,1-b]-thiazole.
AB  - 6-(4'-Fluorophenyl)-5-(4'-pyridyl)-2,3-dihydroimidazo-[2,1-b]-thia zole (SK&F
      86002) is a dual inhibitor of arachidonic acid metabolism which has therapeutic
      potential for the treatment of inflammatory diseases. Previous studies in rats,
      in vivo, demonstrated that SK&F 86002 metabolism proceeds by sequential steps of
      sulfur and nitrogen oxidation. Therefore, these studies were designed to 1)
      identify the enzymes (flavin vs. cytochrome P-450-dependent monooxygenases) which
      were responsible for SK&F 86002 metabolism in vitro in hepatic microsomal
      suspensions from Sprague-Dawley rats, 2) characterize sex-dependent differences,
      and 3) quantitate the effect of pretreatment with SK&F 86002. All three steps in
      the sequential metabolism of SK&F 86002 to the N-oxide sulfone metabolite were
      quantitated individually. The three oxidation steps appeared to be catalyzed
      primarily by cytochrome P-450; heat inactivation (used to destroy flavin
      monooxygenase) had little effect on the metabolism of each compound. Further,N
      octylamine failed to stimulate the metabolism of any compound and the cytochrome
      P-450 inhibitors (SK&F 525-A, metyrapone, and alpha-naphthoflavone) resulted in a
      marked inhibition of the metabolism of all three substrates. Maximal velocities
      for metabolism of all three substrates (SK&F 86002, sulfoxide, and sulfone) in
      microsomes isolated from male rats, were 3- to 5-fold greater than observed in
      female rats. Furthermore, pretreatment of male rats with SK&F 86002 (60 mg/kg/day
      for 3 days) resulted in a change in the in vitro metabolism of all three
      substrates generally characterized by an increase in Vmax and/or a fall in
      km.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1981710
TI  - Absorption of a novel prodrug of L-dopa, L-3-(3-hydroxy-4
      pivaloyloxyphenyl)alanine (NB-355). In vitro and in situ studies.
AB  - Absorption mechanism and absorption site of a prodrug of L-DOPA, L-3-(3-hydroxy-4
      pivaloyloxyphenyl)alanine (NB-355, 1) was investigated using rats. Prodrug 1 (0.5
      mM) was taken up by intestinal tissue segments time-dependently in vitro at pH
      6.0. However, the rate of uptake was less than that of L-dopa. Inhibitors of the
      amino acid active transport system (L-Phe, dinitrophenol, ouabain) had no effect
      on the uptake of prodrug 1. In the intestinal tissue segments, prodrug 1 was
      extensively hydrolyzed by diisopropylfluorophosphate-sensitive esterase(s). To
      characterize the absorption site, gastrointestinal tracts were ligated to make
      acute loops in situ and prodrug 1 or L-dopa was injected into the loops. L-dopa
      disappeared rapidly from the lumen of the jejunum. In contrast, prodrug 1
      disappeared rapidly from the ileum rather than the duodenum or jejunum. From
      these results, it was suggested that prodrug 1 was slowly absorbed primarily from
      the lower small intestine.

PMID- 1981709
TI  - The disposition of 2-cyano-1-methyl 3-(4-(4-methyl-6-oxo-1,4,5,6-tetrahydro
      pyridazin-3-yl)phenyl)guanidine in animals.
AB  - 2-Cyano-1-methyl 3-(4-(4-methyl-6-oxo-1,4,5,6-tetrahydro-pyridazin-3
      yl)phenyl)guan idine (SK&F 94836), a new positive inotrope/vasodilator, is being
      evaluated for the treatment of congestive heart failure. The absorption,
      metabolism, and disposition of the compound have been investigated in the rat,
      mouse, and dog. SK&F 94836 was rapidly absorbed, widely distributed, and rapidly
      and completely excreted primarily via the urine. There was no evidence of
      metabolism of the compound in any of the species studied. The compound showed
      minimal interaction with cytochrome P-450. The compound contains a chiral center.
      The enantiomers have been shown not to interconvert in either rat or dog. The
      serum protein binding was low in all species, including humans, and exhibited no
      stereoselectivity. Studies conducted in rat and dog using constant rate co
      infusion of racemic SK&F 94836 and radiolabeled inulin have demonstrated that
      SK&F 94836 is eliminated by active tubular secretion.

PMID- 1981712
TI  - Thiopurine methyltransferase isozymes in human renal tissue.
AB  - Thiopurine methyltransferase (TPMT) catalyzes the S-methylation of thiopurine
      drugs such as 6-mercaptopurine (6-MP). Levels of TPMT activity in human tissue
      are controlled by a common genetic polymorphism. On a genetic basis, 88.6% of
      humans have high, 11.1% have intermediate, and 0.3% have very low or undetectable
      levels of enzyme activity. Ion exchange chromatography of a pooled human kidney
      preparation yielded two peaks of TPMT activity. Approximately 83-88% of the
      enzyme activity eluted as a major peak (peak I), while 12-17% eluted in a
      distinct second peak (peak II). Each of these isozymes was then purified further
      by gel filtration chromatography. The two isozymes had similar pH optima, similar
      KM values for the reaction co-substrates, 6-MP and S-adenosyl-L-methionine, and
      similar Ki and Ks values for the TPMT inhibitor 3,4-dimethoxy-5-hydroxybenzoic
      acid. Electrophoretic mobilities of the two isozymes were identical, and both had
      molecular weights of approximately 30,000. To determine whether tissue from
      individual subjects with different presumed genotypes for the TPMT genetic
      polymorphism contained one, the other, or both isozymes, TPMT activities were
      measured in renal preparations from 48 patients. Of these patients, 40 (83%) had
      high and 8 (16%) had intermediate levels of activity. Ion exchange chromatography
      of renal preparations from three individuals with intermediate and three
      individuals with high TPMT activities showed that all six samples contained both
      isozymes in similar proportions. Our results demonstrate that two isozymes of
      TPMT are present in the human kidney.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1981711
TI  - The formation, disposition, and hepatic metabolism of dimethylnitrosamine in the
      pig.
AB  - The disposition, metabolism, and endogenous formation of N-nitrosodimethylamine
      (NDMA) from nitrosatable precursors was studied in the intact pig and in animals
      with cannulated hepatic and portal veins and catheterized bile ducts. Rates of
      disappearance of NDMA from peripheral venous and arterial blood after iv
      injections were virtually identical and the compound appeared in bile after a lag
      time of about 1 hr, with a subsequent decline in biliary concentration at about
      the same rate as in circulating blood. Measurements of NDMA in portal and hepatic
      vein blood after oral doses of 10, 1.0 and 0.1 mg/kg, respectively, showed
      progressively greater hepatic extraction with levels in the hepatic vein
      approaching the limits of detection after the lowest dose. Both halothane and
      ethanol virtually abolished the hepatic extraction of NDMA, presumably due to
      their known inhibitory action on its metabolism in the liver. Endogenous
      formation of NDMA and N-nitrosomorpholine after oral doses of the amines plus
      nitrite was demonstrated by their detection and measurement in the portal vein
      blood. Morpholine was nitrosated more effectively than dimethylamine and
      inhibited the nitrosation of the latter when the two amines were given together.
      NDMA was found in the portal blood after sequential oral administration of
      aminopyrine and nitrite, the concentration being considerably greater after
      fasting for 24 hr than after a 2-hr fast when much food was present in the
      stomach.

PMID- 1981714
TI  - Identification and distribution in the rat of acidic metabolites of tamoxifen.
AB  - Chromatographic analysis of acidic fractions of urinary radioactivity from
      immature female rats which had received the triarylethylene antiestrogen
      tamoxifen (TAM), labeled with 14C, resulted in the identification of two new
      metabolites. These were tamoxifen acid (TA), in which the side chain of TAM was
      changed to an oxyacetic acid moiety, and 4-hydroxytamoxifen acid (4-HTA), which
      had a similarly altered side chain plus a phenolic hydroxy group in its
      structure. In contrast to other TAM metabolites and other arylacetic acids,
      neither TA nor 4-HTA were eliminated as glucuronic acid or glycine conjugates in
      urine. Only small amounts of acidic radioactivity were found in liver tissue 24
      and 48 hr after dosing, and none was detected in uterine tissue. However, TA plus
      4-HTA accounted for 2.8% and 2.9% of the administered dose eliminated within 24
      hr in urine and feces, respectively. These results suggest that TA and 4-HTA are
      important final products of TAM metabolism and that these, unlike other
      hydroxylated and/or dealkylated metabolites of this drug, may not contribute to
      the antiuterotrophic effects of TAM.

PMID- 1981713
TI  - Covalent binding of zomepirac glucuronide to proteins: evidence for a Schiff base
      mechanism.
AB  - Carboxylic acids can undergo irreversible binding to proteins via their acyl
      glucuronide metabolites. Such binding occurs in humans and in vitro for bilirubin
      and the anti-inflammatory drugs zomepirac and tolmetin and may have toxicological
      significance. The mechanism of the binding is uncertain, but is thought to
      involve nucleophilic displacement of glucuronic acid by free cysteine thiols,
      tyrosine, or lysine residues of the protein. We now present evidence, using
      zomepirac glucuronide, for an alternative mechanism where irreversible binding
      occurs by isomerization of the glucuronide and formation of an imine linkage
      between the glucuronic acid moiety of the conjugate and a lysine or terminal
      amino group of the protein. Involvement of a protein thiol in the binding
      mechanism was ruled out by experiments with the thiol blocking agent, p
      hydroxymercuribenzoate. Moreover, significant irreversible binding occurred when
      the cysteine free protein, alpha s1-casein, was incubated in solution with
      zomepirac glucuronide in vitro. When zomepirac glucuronide was added to solutions
      with albumin in the presence of the imine trapping reagent, sodium cyanide, or
      the reducing agent, sodium cyanoborohydride, irreversible binding of zomepirac
      increased 8.3- and 5.5-fold relative to controls, respectively, after 6 hr at 37
      degrees C. The product formed after treatment of solutions of zomepirac
      glucuronide and albumin with sodium cyanoborohydride was stable in dilute acid,
      whereas similar acid treatment of zomepirac-albumin adduct from control
      incubations, obtained after sodium cyanide exposure, released 30% of the total
      adduct. Only isomeric conjugates of zomepirac glucuronide were released from
      zomepirac-albumin adduct by mild acid; no beta 1-isomer was detected.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1981715
TI  - Pharmacokinetics of the anti-AIDS drug 2',3'-dideoxyinosine in the rat.
AB  - The pharmacokinetics of 2',3'-dideoxyinosine (ddlno) was examined in the male
      Fischer 344 rat using reversed phase HPLC with UV and radiochemical detection.
      Following iv doses of 12, 25, and 100 mg/kg, the parent drug was rapidly
      eliminated from plasma (mean residence time, 6.3 min; systemic clearance, 64
      ml/min/kg). The mean terminal elimination half-life was 28 min and the volume of
      distribution at steady state was 0.39 liter/kg. Orally administered [3H]ddlno
      (100 mg/kg) was not significantly bioavailable in the rat, with only 8-11% of the
      dose absorbed as the parent compound over a 2 hr period. Peak plasma drug
      concentrations occurred 10 to 20 min following oral administration. Solution
      stability data suggested that ddlno was unstable at gastric pH (pH 1, t1/2 less
      than 30 sec). However, elevation of gastric pH with sodium bicarbonate prior to
      oral administration of ddlno was not effective in increasing the bioavailability
      of the parent drug. The drug and its metabolic products were extensively
      distributed into rat tissue 48 hr after iv or oral administration. Following iv
      infusion of [3H]ddlno to steady state conditions, the highest tissue-to-plasma
      ratios of radioactivity were found in the kidney (2.2), liver (1.7), and spleen
      (1.5). Renal clearance accounted for 99% of the eliminated dose. Liver perfusion
      studies showed that ddlno was not subject to significant hepatic clearance (less
      than 10%) and that the metabolism was not inducible with phenobarbital.

PMID- 1981716
TI  - Metabolism and cytotoxicity of acetaminophen in hepatocyte cultures from rat,
      rabbit, dog, and monkey.
AB  - Acetaminophen (APAP)-induced cytotoxicity and metabolism were studied in
      hepatocyte cultures isolated from the rat, rabbit, dog, and monkey. Cytotoxicity
      was evaluated by morphological examination and by alanine aminotransferase and
      aspartate aminotransferase released into the cell culture medium. The toxicity
      results obtained by these two methods were in agreement and can be explained by
      the biotransformation of APAP in each species. Rat and dog hepatocyte cultures
      contained the most APAP-sulfate conjugates, while the rabbit, dog, and monkey
      hepatocyte cultures contained the most APAP-glucuronide conjugates. The
      percentage of APAP-glutathione conjugate was very low in all species, indicating
      that either very little of the toxic APAP metabolite, N-acetylbenzoquinoneimine,
      was formed, or in the species susceptible to N-acetylbenzoquinoneimine-induced
      cytotoxicity, the glutathione S-transferase activity or the amount of glutathione
      was low. Rabbit hepatocytes transformed the most APAP during both short and long
      periods of exposure. Of the four species, the dog hepatocytes exhibited the
      highest level of APAP-induced cytotoxicity. The sensitivity of dog hepatocytes to
      APAP may be due to their low conjugating enzyme activity. Rat hepatocytes
      utilized all three pathways of APAP-biotransformation to prevent APAP-induced
      cytotoxicity. Monkey hepatocyte cultures had a very large capacity to transform
      APAP to a glucuronide conjugate and a very high level of glutathione S
      transferase activity, and therefore did not exhibit any cytotoxicity. These
      studies indicate that the competing pathways of APAP conjugation in hepatocyte
      cultures from different species explain the differences observed in APAP-induced
      cytotoxicity.

PMID- 1981717
TI  - Metabolism of the carcinogen 3-methylcholanthrene in human bone marrow
      preparations.
AB  - The metabolism of 3-methylcholanthrene was investigated by incubating the
      hydrocarbon with human bone marrow preparations in air for 60 min at 37 degrees
      C. The major metabolites were identified by HPLC and GC/MS as 1-hydroxy-3
      methylcholanthrene, 1-keto-3-methylcholanthrene, and cholanthrene. The results
      demonstrate that the potent carcinogen, 3-methylcholanthrene, can undergo
      biochemical reactions in preparations of human bone marrow, giving rise to the
      formation of metabolites which are known to be carcinogenic in rats and mice.

PMID- 1981718
TI  - Pharmacokinetics of codeine after parenteral and oral dosing in the rat.
AB  - The pharmacokinetics of codeine was examined in six male Sprague-Dawley rats
      following iv bolus (3 mg/kg) and oral (5 mg/kg) codeine in a randomized crossover
      design. Whole blood concentrations of codeine and its O-demethylated metabolite,
      morphine, were determined by HPLC with electrochemical detection. Following iv
      codeine administration, the distribution and elimination are best described by an
      open two-compartment model. The weight normalized volume of distribution of
      (Vdarea) and total body clearance (CL) were 5.1 +/- 1.7 liters/kg and 6.2 +/- 1.5
      liters/kg/hr, respectively. Mean residence time of codeine averaged 34.1 +/- 6.9
      minutes. The ratio of AUCmorphine/AUCcodeine was 0.05 +/- 0.02. The absolute
      bioavailability of codeine calculated was 8.3 +/- 3.2%, indicating extensive
      first pass metabolism of codeine. An equivalent amount of codeine and morphine
      were present in the rat following oral codeine. Thus, the amount of morphine
      formed following codeine administration depends on the route of codeine
      administration.

PMID- 1981719
TI  - Pharmacokinetics of a novel butylated hydroxytoluene-thiazolidinone CNS
      antiischemic agent LY256548 in rats, mice, dogs, and monkeys.
AB  - Mice, rats, dogs, and monkeys were given a single 50 mg/kg oral dose of
      [14C]LY256548. Plasma levels of radioactivity and LY256548 were determined, as
      was the excretion of radioactivity. Peak plasma levels of LY256548 occurred prior
      to those of radioactivity in mice, dogs, and monkeys, but were coincident in
      rats. The Cmax of LY256548 in rats, mice, dogs, and monkeys was 0.17, 0.30, 0.04,
      and 0.02 microgram/ml, respectively. However, the Cmax of radioactivity was 10
      fold greater than that of LY256548 in rats and mice, 24-fold greater in dogs, and
      40-fold greater in monkeys. The half-lives of LY256548 were substantially less
      than those of radioactivity in all four species. The oral absorption of LY256548
      in rats, dogs, and monkeys was 45%, 7%, and 12%, respectively. The systemic
      bioavailability of LY256548 in rats, dogs, and monkeys was 6%, 0.4%, and 3%,
      respectively. Extensive biotransformation of LY256548 was observed in all four
      species. Fecal excretion of radioactivity was the primary mode of elimination,
      being 95% in rats, 81% in mice, 100% in dogs, and 68% in monkeys.

PMID- 1981720
TI  - Acetylator genotype-dependent expression of arylamine N-acetyltransferase and N
      hydroxyarylamine O-acetyltransferase in Syrian inbred hamster intestine and
      colon. Identity with the hepatic acetylation polymorphism.
AB  - Human epidemiological studies suggest an association between rapid acetylator
      phenotype and the incidence of colorectal cancer. Genetic regulation of acetyl
      coenzyme A-dependent N-acetyltransferase (NAT) and O-acetyltransferase (OAT)
      enzymatic activities may play a role in the metabolic activation of arylamine
      chemicals in the intestine and colon. In this study, the inheritance of
      acetyltransferase activity in the intestine and colon was investigated in the
      Syrian inbred hamster model. Relatively high levels of both arylamine NAT and N
      hydroxyarylamine OAT activities were expressed in hamster intestine and colon
      cytosols, at levels similar to those in the liver. Acetylator genotype-dependent
      levels of NAT activity were expressed towards p-aminobenzoic acid and the
      carbocyclic arylamine carcinogens 2-aminofluorene (AF), 4-aminobiphenyl, and beta
      naphthylamine. However, acetylator genotype-independent activity was found with
      the heterocyclic arylamine carcinogens 2-aminodipyrido[1,2-a:3',2'd]imidazole, 3
      amino-1-methyl-5H-pyrido[4,3-b]indole, and 2-amino-9H-pyrido-[2,3,b]indole. F1
      hybrid heterozygous acetylator progeny expressed unimodal levels of
      acetyltransferase activity intermediate between the homozygous rapid and slow
      acetylator parental strains. F2 generation progeny segregated into three modes
      (low, intermediate, and high) in a ratio of 1/2/1, and both sets of backcrosses
      yielded bimodal distributions of low and intermediate or high and intermediate in
      equal ratios. The genetic data is consistent with simple autosomal Mendelian
      inheritance of two codominant alleles (rapid and slow) at a single genetic locus,
      the polymorphic acetyltransferase gene. Levels of N-hydroxy-2-aminofluorene OAT
      activity were acetylator genotype-dependent in liver, intestine, and colon
      cytosols, which correlated well with AF NAT activity.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1981721
TI  - Stereochemical differences in the metabolism of 3,4-methylenedioxymethamphetamine
      in vivo and in vitro: a pharmacokinetic analysis.
AB  - The in vivo N-demethylation of (+) and (-)3,4-methylenedioxymethamphetamine
      (MDMA) to 3,4-methylenedioxyamphetamine (MDA) was determined and the
      pharmacokinetic relationship between the two compounds calculated. The levels of
      MDA formed after iv administration of (+)MDMA to male rats were about 3 times
      greater than those for (-)MDMA, although the plasma levels of the parent drugs
      were comparable. Plasma MDA concentrations were lower in phenobarbital-pretreated
      rats, but SKF 525-A pretreatment, at the dose used, had minimal effects. In liver
      microsome experiments conducted with microM concentrations of (+)MDMA, 3,4
      dihydroxymethamphetamine (N-methyl-alpha-methyldopamine) was shown to be the
      major metabolite. MDA was also formed in vitro, but the enantioselectivity was
      the opposite of that found in vivo, pointing out the difficulties in
      extrapolation of in vitro observations to in vivo disposition. The high levels of
      MDA observed after administration of (+)MDMA to intact animals suggest that this
      active metabolite could be important in the overall effects of (+)MDMA.

PMID- 1981722
TI  - Glucuronidation of 2-arylpropionic acids pirprofen, flurbiprofen, and ibuprofen
      by liver microsomes.
AB  - Acylglucuronide formation from the 2-arylpropionic acids pirprofen, flurbiprofen,
      and ibuprofen, three nonsteroidal anti-inflammatory drugs (NSAIDs), was
      investigated in rat liver microsomes using an HPLC method and 14C-labeled UDP
      glucuronic acid as co-substrate. Pirprofen was the best substrate of UDP
      glucuronosyltransferase with a Vmax/Km of 45.4, as compared with 8.0 and 1.6 for
      flurbiprofen and ibuprofen, respectively. Glucuronidation of the drugs was
      significantly increased upon treatment of rats with phenobarbital; 3
      methylcholanthrene or clofibrate failed to induce the activity. At the dose of
      100 mg/kg body weight for 1, 3, and 5 days, pirprofen was unable to induce its
      own glucuronidation. However, this treatment caused a transient increase, after 1
      day, of several isoform activities monitored with 4-nitrophenol, 1-naphthol, 4
      methylumbelliferone, terpenes, and testosterone as substrates. After 3 and 5 days
      these activities were decreased, especially when glucuronidation of 4-nitrophenol
      and 4-methylumbelliferone was considered, glucuronidation of the terpenes cis
      myrtanol, borneol, nopol, and of testosterone being similar to control values. By
      contrast to clofibrate, administration of pirprofen to rats decreased bilirubin
      UDP-glucuronosyltransferase in a time-dependent fashion with a maximal decrease
      of 59% after 5 days. Treatment of rats with pirprofen also decreased markedly the
      formation of flurbiprofen glucuronide. Comparison of NSAID glucuronidation
      between several species indicated that it was most potent in monkeys, dogs, and
      humans. Cats were also efficient in that respect. Gunn rats, which are
      genetically deficient in bilirubin glucuronidation, were able to form
      acylglucuronides from the drugs, thus indicating that these 2-arylpropionic acids
      were not substrates of the bilirubin isozyme.

PMID- 1981723
TI  - Identification of DP-1904 and its ester glucuronide in human urine and
      determination of their enantiomeric compositions by high-performance liquid
      chromatography with optical activity and ultraviolet detection.
AB  - The parent compound and one metabolite have been isolated from urine of five
      healthy male volunteers who received a single 200 mg oral dose of DP-1904. These
      compounds were extracted by using a Sep-Pak C18 cartridge and purified by the
      preparative HPLC method. On the basis of proton magnetic resonance and mass
      spectral data, unchanged drug and its ester glucuronide have been identified in
      human urine. DP-1904 has one asymmetric carbon and is used as a racemate in the
      current clinical trial. The enantiomeric compositions of unchanged DP-1904 and
      aglycon of DP-1904 glucuronide were determined by HPLC with optical activity and
      ultraviolet detection. The (R)-(+)-enantiomer percentages in unchanged DP-1904
      and aglycon of its ester glucuronide in human urine collected at 0-4 hr after
      oral dosing were 60 +/- 1.3% and 38 +/- 1.4% (mean +/- SE, n = 5), respectively.
      The 0-4 hr urine collection represented approximately 80% of the given dose.
      These studies demonstrate that DP-1904 undergoes stereoselective disposition in
      humans. However, the difference in urinary excretion between DP-1904 enantiomers
      was rather small.

PMID- 1981724
TI  - Biotransformation of sufentanil in liver microsomes of rats, dogs, and humans.
AB  - The biotransformation of sufentanil (SUF), an analog of the synthetic opioids
      fentanyl and alfentanil, was investigated in liver microsomes of rats, dogs, and
      humans. The drug was extensively metabolized and the metabolism was found to be
      very similar, both kinetically and metabolically, in the three species. The
      initial metabolism of SUF occurred monophasically in man and dog and biphasically
      in the rat over a concentration range of 0.13-20.1 microM. The apparent Vm values
      were 7.30 and 6.15 nmol metabolized.min-1.mg protein-1, and the apparent Km
      values were 4.98 microM and 15.2 microM for dog and human microsomes,
      respectively. In rat microsomes, apparent Km values were 0.10 and 20.8 microM,
      and the apparent Vm values were 0.10 and 7.32 nmol metabolized.min-1.mg protein-1
      for the high and low affinity site, respectively. The major metabolic pathways
      were similar in the three species and included oxidative N-dealkylation at the
      piperidine nitrogen, oxidative N-dealkylation of the piperidine ring from the
      phenylpropanamide nitrogen, oxidative O-demethylation, and aromatic
      hydroxylation. Desmethyl-SUF was formed at the shorter incubation times but
      quickly metabolized into secondary metabolites. The major metabolites which could
      be detected at the end of the incubation were N-[4-(methoxymethyl)-4-piperidinyl]
      N-phenylpropanamide, N-[4-(hydroxymethyl)-4-piperidinyl]-N-phenylpropanamide, and
      N-phenylpropanamide. The relevance of the in vitro results is discussed in
      relation to previous in vivo studies of the metabolism of SUF in rats, dogs, and
      humans.

PMID- 1981726
TI  - Metabolism of benzene in rat hepatocytes. Influence of inducers on phenol
      glucuronidation.
AB  - Alterations of benzene metabolism in liver markedly influence benzene toxicity at
      extrahepatic target tissues. Therefore, generation of 11 phase I and II
      metabolites of benzene (including phenol, hydroquinone, catechol, benzene-1,2
      dihydrodiol, their sulfates and glucuronides, and phenylglutathione) was compared
      in hepatocytes from 3-methylcholanthrene (MC)- or phenobarbital-treated rats and
      from untreated controls. At 0.1 mM benzene, total metabolism appeared to be
      unchanged by treatment with inducers. Phenylsulfate (35%), phenylglucuronide
      (15%), and phenylglutathione (12%) represented the major metabolites in
      hepatocytes from untreated controls. With hepatocytes from MC-treated rats, a
      pronounced shift from phenylsulfate to phenylglucuronide (increase to 34%) was
      observed, while the formation of unconjugated phenol, hydroquinone, and catechol
      was decreased (from 16 to 10%). A similar shift from sulfation to glucuronidation
      was seen in similar studies with phenol. Lineweaver-Burk analysis of microsomal
      phenol UDP-glucuronosyltransferase activity suggested that MC-treatment induced a
      high affinity isozyme (KM = 0.14 mM), in addition to the low affinity isozyme (KM
      = 3.1 mM) present in liver microsomes from untreated and phenobarbital-treated
      rats. It is concluded that induction by MC of a high affinity hepatic phenol UDP
      glucuronosyltransferase effectively shifts benzene metabolism toward formation of
      less toxic metabolites. This shift may reduce toxic risks at extrahepatic target
      tissues.

PMID- 1981727
TI  - Distribution and disposition of trospectomycin sulfate in the in vivo rat,
      perfused rat liver, and cultured rat hepatocytes.
AB  - Trospectomycin sulfate is an experimental, aminocyclitol antibiotic. It has been
      shown in preclinical, chronic safety studies in the dog and rat to elicit a
      reversible, lysosomal phospholipidosis in liver. The present experiments were
      conducted to characterize the tissue distribution and disposition of
      3H]trospectomycin sulfate in the male rat, perfused rat, perfused rat liver, and
      cultured rat hepatocytes. Following a 5 mg/kg iv dose to four rats, approximately
      70% of the dose was recovered within 24 hr primarily in urine as unchanged drug,
      and the remainder was eliminated with a terminal phase half-life in blood and
      tissues of 3 days. Fecal excretion was relatively minor (16% of the dose
      recovered in feces in 7 days) until later timepoints, when it was the principal
      pathway of terminal phase elimination. The liver sequestered approximately 10% of
      the dose and had the highest tissue levels of drug at all times measured. Liver
      perfusion experiments indicated that trospectomycin accumulated in a hepatic
      depot compartment as parent drug by a first-order process which was nonsaturable
      up to a 1 mM concentration of drug. Biliary excretion of unchanged trospectomycin
      by the perfused liver was slow (approximately 3% of the dose in 2 hr) and
      occurred by both paracellular and transcellular mechanisms. The hepatic depot
      compartment appeared to be responsible for transcellular biliary excretion, and
      thus for the sustained fecal excretion observed in vivo. Subcellular distribution
      experiments indicated that at least 50% of the drug in the hepatic depot was
      sequestered in organelles having a broad density range. The existence of a
      trospectomycin depot compartment was also demonstrated in cultured
      hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1981725
TI  - Identification of the rabbit and human cytochromes P-450IIIA as the major enzymes
      involved in the N-demethylation of diltiazem.
AB  - Oxidative metabolism of diltiazem (DTZ), a calcium channel blocker, was
      investigated in rabbit and human liver microsomes as well as in primary cultures
      of human hepatocytes. DTZ N-demethylation, the major metabolic pathway in man,
      was strongly increased by treatment of animals, patients, and hepatocyte cultures
      with rifampicin and other inducers of the P-450IIIA subfamily. In a reconstituted
      system with purified forms of P-450 and NADPH cytochrome P-450 reductase, P
      450IIIA7 exhibited the highest DTZ N-demethylase activity. In both rabbit and
      human liver microsomes, this activity was highly correlated with erythromycin
      demethylase, a characteristic substrate of P-450IIIA, or with an
      immunoquantitated level of P-450IIIA, and was specifically inhibited by anti-P
      450IIIA7 polyclonal and monoclonal antibodies. Cyclosporin A, another specific
      substrate of P-450IIIA in rabbit and human, competitively inhibited DTZ N
      demethylase in both species. In primary cultures of human hepatocytes treated
      with various inducers, including rifampicin, dexamethasone, phenobarbital,
      phenylbutazone or beta-naphthoflavone, the rate of release of N-demethyl-DTZ in
      the extracellular medium was highly correlated with the intracellular level of P
      450IIIA, which appeared to be strongly induced by rifampicin and phenobarbital
      and to a lesser extent by dexamethasone and phenylbutazone. In aggregate, these
      results are consistent with the view that in both rabbit and human, cytochromes P
      450 from the P-450IIIA subfamily are the major enzymes involved in the N
      demethylation of DTZ. Accordingly, drugs which may be specific substrates or
      inducers of this P-450 are likely to influence both the side effects and the
      efficacy of this molecule.

PMID- 1981729
TI  - The identification of urinary metabolites of doxepin in patients.
AB  - The metabolism of doxepin was investigated in three patients who provided
      cumulative urine samples on each of 3 successive days. These samples were
      examined by means of stereoselective HPLC or HPLC combined with mass spectrometry
      through a plasmaspray interface (LCMS). In addition, sufficient quantities of the
      major metabolites were isolated from the urine by column chromatography. The
      isolated metabolites were examined by HPLC, proton nuclear magnetic resonance
      spectroscopy (1H-NMR), and chemical ionization and/or electron impact mass
      spectrometry (EIMS). The resultant spectra and chromatographic properties were
      compared with authentic reference standards. The metabolites were identified as
      (E)-2-hydroxydoxepin, (E)-2-hydroxy-N-desmethyldoxepin, (Z)- and (E)-N
      desmethyldoxepin, and (Z)- and (E)-doxepin N-oxide. There was no evidence of
      hydroxylation at the oxymethylene bridge. A further metabolite previously
      unreported was tentatively identified by LCMS and EIMS as an aromatic hydroxy-N
      desmethyldoxepin hydrated at the exocyclic double bond. This metabolite was
      present in very low amounts, precluding its analysis by 1H-NMR. Moreover, this
      type of compound dehydrated readily in vitro, and numerous attempts to synthesize
      reference materials were unsuccessful. The tentative identification of this
      hydrated metabolite lends significant support to a possible mechanism responsible
      for the enrichment of cis-N-desmethyldoxepin over time in plasma.

PMID- 1981728
TI  - Influence of a single dose of ethanol on the kinetics of valproic acid in rats.
AB  - A study was made of the influence of ethanol on the kinetics of valproic acid
      (VPA) in rats that received single doses of both compounds. Three groups of
      animals received a single dose of VPA (100 mg/kg) through a gastric tube, alone
      (Group I: controls) or together with ethanol at doses of 2.5 mg/kg (Group IIa)
      and 5 mg/kg (Group IIb). VPA was determined using the homogeneous immunoassay
      EMIT. VPA kinetics were fitted to an open two-compartment model with a first
      order two phase absorption process defined by the constants Ka1 and Ka2, where
      Ka1 would reflect the rate of gastric emptying, and Ka2 could express the true
      absorption constant. The groups of animals receiving ethanol showed a
      statistically significant decrease (p less than 0.05) in plasma concentrations of
      VPA compared with the control group. Ka2 increased in groups IIa and IIb compared
      with the control group (35.79 hr-1 and 36.61 hr-1 vs. 28.18 hr-1). However, Ka1
      decreased in group IIb as compared with the control rats (2.34 hr-1 vs. 4.18 hr
      1), whereas no modifications were seen in group IIa (4.35 hr-1). The t1/2 beta
      was greater in groups IIa and IIb than in the controls (8.77 hr and 7.78 hr vs.
      4.55 hr), and Ke was lower in those groups than in the controls (0.86 hr-1 and
      0.48 hr-1 vs. 0.98 hr-1), suggesting a decrease in the elimination of VPA
      following administration of a single dose of ethanol.

PMID- 1981730
TI  - Induction of cytochrome P-450 isozyme 3a (P-450IIE1) in rabbit olfactory mucosa
      by ethanol and acetone.
AB  - Cytochrome P-450 isozyme 3a, the alcohol-inducible form of cytochrome P-450 (P
      450IIE1), was previously identified in rabbit nasal microsomes with the use of
      immunochemical techniques; the occurrence of this cytochrome in the nasal mucosa
      was subsequently confirmed through RNA hybridization experiments. However, in
      contrast to the well established inducibility of isozyme 3a in liver and kidney
      by alcohol treatment of the animals, no induction was observed in the nasal
      tissue with the use of a polyclonal anti-3a antibody for immunochemical
      quantitation. Recently, two new P-450 isozymes, designated NMa and NMb, were
      identified in rabbit nasal microsomes, and were found to have overlapping
      substrate specificity with isozyme 3a. Moreover, the two new cytochromes cross
      react with the polyclonal anti-3a antibody that was used in the earlier study for
      quantitation of nasal isozyme 3a. These recent findings invalidate our previous
      conclusion that isozyme 3a is not induced by ethanol treatment of rabbits. In the
      present study, immunoblot quantitation of isozyme 3a was performed with a
      monoclonal anti-3a antibody that does not recognize either NMa or NMb, and the
      nasal microsomal metabolism of butanol was examined at various substrate
      concentrations. We have found that the level of isozyme 3a protein in nasal
      mucosa is elevated about 2-fold after treatment of the animals with ethanol and
      about 6-fold after treatment with acetone. Furthermore, corresponding increases
      in the rate of microsomal butanol oxidation were observed at low substrate
      concentrations. Thus, we conclude that P-450 isozyme 3a is, in fact, inducible in
      the nasal tissues by ethanol or acetone treatment of rabbits.

PMID- 1981731
TI  - Excretion and metabolism of recainam, a new anti-arrhythmic drug, in laboratory
      animals and humans.
AB  - The metabolic disposition of recainam, an antiarrhythmic drug, was compared in
      mice, rats, dogs, rhesus monkeys, and humans. Following oral administration of
      [14C]recainam-HCl, radioactivity was excreted predominantly in the urine of all
      species except the rat. Metabolite profiles were determined in excreta by HPLC
      comparisons with synthetic standards. In rodents and rhesus monkeys, urinary
      excretion of unchanged recainam accounted for 23-36% of the iv dose and 3-7% of
      the oral dose. Aside from quantitative differences attributable to presystemic
      biotransformation, metabolite profiles were qualitatively similar following oral
      or iv administration to rodents and rhesus monkeys. Recainam was extensively
      metabolized in all species except humans. In human subjects, 84% of the urinary
      radioactivity corresponded to parent drug. The major metabolites in mouse and rat
      urine and rat feces were m- and p-hydroxyrecainam. Desisopropylrecainam and
      dimethylphenylaminocarboxylamino propionic acid were the predominant metabolites
      in dog and rhesus monkey urine. Small amounts of desisopropylrecainam and p
      hydroxyrecainam were excreted in human urine. Selective enzymatic hydrolysis
      revealed that the hydroxylated metabolites were conjugated to varying degrees
      among species. Conjugated metabolites were not present in rat urine or feces,
      while conjugates were detected in mouse, dog, and monkey urine. Structural
      confirmation of the dog urinary metabolites was accomplished by mass spectral
      analysis. The low extent of metabolism of recainam in humans suggests that there
      will not be wide variations between dose and plasma concentrations.

PMID- 1981732
TI  - Metabolism of 2-chloro-1,1-difluoroethene to glyoxylic and glycolic acid in rat
      hepatic microsomes.
AB  - The complete metabolic fate of the volatile anesthetic halothane is unclear since
      2-chloro-1,1-diflurorethene (CDE), a reductive halothane metabolite, is known to
      readily release inorganic fluoride upon oxidation by cytochrome P-450. This study
      sought to clarify the metabolism of CDE by determining its metabolites and the
      roles of induce cytochrome P-450 forms in its metabolism. Upon incubation of
      [14C]CDE with rat hepatic microsomes, two major radioactive products were found
      which accounted for greater than 94% of the total metabolites. These compounds
      were determined to be the nonhalogenated compounds, glyoxylic and glycolic acids,
      which were formed in a ratio of approximately 1 to 2 of glyoxylic to glycolic
      acid. No other radioactive metabolites could be detected. Following incubation of
      CDE with hepatic microsomes isolated from rats treated with cytochrome P-450
      inducers, measurement of fluoride release showed that phenobarbital induced CDE
      metabolism to the greatest degree at high CDE levels, isoniazid was the most
      effective inducer at low CDE concentrations, and beta-naphthoflavone was
      ineffective as an inducer. These results suggest that CDE biotransformation
      primarily involves the generation of an epoxide intermediate, which undergoes
      mechanisms of decay leading to total dehalogenation of the molecule, and that
      this metabolism is preferentially carried out by the phenobarbital- and ethanol
      inducible forms of cytochrome P-450.

PMID- 1981733
TI  - Interaction of cotinine with rat hepatic microsomal P-450. Comparison with
      metyrapone and immunomodulation of cotinine and metyrapone binding by monoclonal
      anti-cotinine antibodies.
AB  - The ability of the major nicotine metabolite, cotinine, to interact with rat
      liver microsomal cytochrome P-450 and the immunomodulatory effects of anti
      cotinine antibodies were studied. Cotinine induced type II spectral changes with
      both microsomes from phenobarbital (PB)-induced rats and purified P-450 with
      apparent Ks values of 97 and 750 microM, respectively. In contrast, the Ks value
      was 0.3 microM for metyrapone and 5 microM for nicotine with both the microsomes
      and purified enzyme. The apparent Ki value for cotinine inhibition of 7
      pentoxyresorufin O-dealkylase activity with the microsomes (87 microM) was
      approximately 87- and 870-fold higher than for nicotine and metyrapone,
      respectively. Monoclonal antibodies produced against cotinine cross-reacted
      equally well with metyrapone. They specifically blocked enzyme binding of both
      drugs based on dose-dependent inhibition of spectral changes, and reversed the
      metyrapone-induced inhibition of microsomal O-dealkylase activity. In contrast,
      antibodies to nicotine did not cross-react with cotinine or metyrapone and had no
      effect on their activity, although they did block the action of nicotine. These
      results demonstrate that cotinine binding to P-450 from PB-induced rats and
      inhibition of functional activity in vitro are qualitatively like the effects of
      metyrapone and nicotine, and that monoclonal anti-cotinine antibodies are useful
      molecular probes of the interactions between cotinine and metyrapone with the
      enzyme.

PMID- 1981734
TI  - Hepatic protein arylation, glutathione depletion, and metabolite profiles of
      acetaminophen and a non-hepatotoxic regioisomer, 3'-hydroxyacetanilide, in the
      mouse.
AB  - The metabolism and disposition of acetaminophen (APAP) and a non-hepatotoxic
      regioisomer, 3'-hydroxyacetanilide (AMAP), were investigated in the mouse using
      14C-labeled analogues. Covalent binding of metabolites of both compounds was
      observed on the order of 1 nmol/mg tissue protein. AMAP binding was much higher
      than that of APAP at 1 hr, but by 24 hr, AMAP binding was significantly lower
      than that of APAP. APAP binding peaked at 3 hr and did not decrease significantly
      thereafter. Despite the high early levels of covalent binding, AMAP was not as
      effective in causing glutathione depletion as was APAP. This was reflected in the
      urinary metabolite profiles of the two compounds. Approximately twice as much
      APAP was cleared through thioether conjugation compared to AMAP, based on an
      analysis of urinary metabolites. These results and results of other studies
      suggest that electrophilic metabolites of AMAP are more reactive than those of
      APAP, and do not diffuse as far from their site of formation, which may spare
      some critical target proteins from damage.

PMID- 1981735
TI  - Metabolism of 1,1-dichloro-cis-diphenylcyclopropane by rat liver microsomes.
AB  - The metabolic fate of the anti-estrogen 1,1-dichloro-cis-diphenylcyclopropane
      (Analog II), was studied in vitro with phenobarbital-induced rat liver microsomal
      fractions. The presence of five metabolites was directly or indirectly
      established. Biotransformation products were isolated by TLC and HPLC techniques
      and, when possible, the structures were confirmed through comparison with
      synthetic samples. The presence of an allyl chloride, highly reactive, metabolic
      intermediate was stated.

PMID- 1981736
TI  - Identification of the urinary metabolites of tacrine in the rat.
AB  - Tacrine (THA) is a potent cholinesterase inhibitor being studied for the
      treatment of Alzheimer's disease. The metabolism and excretion of THA were
      studied in rats following a single oral dose of 20 mg/kg of THA. The results show
      THA was extensively metabolized in rats after oral administration. Three major
      urinary metabolites were isolated by HPLC on a semi-prep analytical phenyl
      column, and subsequent purification of the individual fractions on a semi-prep
      analytical cyano column. The major metabolic pathways involve the hydroxylation
      of the saturated ring at positions 1, 2, and 4. The structures of the metabolites
      9-amino-1,2,3,4-tetrahydroacridin-1-ol (1-OH-THA), 9-amino-1,2,3,4
      tetrahydroacridin-2-ol (2-OH-THA), and 9-amino-1,2,3,4-tetrahydroacridin-4-ol (4
      OH-THA) were determined by electron impact mass spectrometry and/or 1H-NMR, and
      compared with synthetic references. The urinary excretion of THA and metabolites
      was quantitated by HPLC with UV detection. About 60% of the oral dose was
      eliminated as total THA, 1-OH-THA, 2-OH-THA, and 4-OH-THA over a 48-hr collection
      interval; and the non-conjugated THA and hydroxylated metabolites accounted for
      45% of the dose.

PMID- 1981737
TI  - Hepatic microsomal metabolism of sulfamethoxazole to the hydroxylamine.
AB  - Sulfonamides are oxidized to protein reactive cytotoxic metabolites by murine
      hepatic microsomes. Mononuclear leukocytes from patients with idiosyncratic
      reactions to sulfonamides were more susceptible to toxicity from these
      metabolites than were leukocytes from a control population, suggesting that these
      metabolites play a role in the pathogenesis of such reactions. Here we have shown
      that murine hepatic microsomes oxidize sulfamethoxazole at the N4-position to
      form the hydroxylamine. Formation of the hydroxylamine was dependent on the
      presence of microsomes, NADPH, and oxygen. The addition of SKF 525-A, cimetidine,
      or gassing with carbon monoxide inhibited formation. The enzymic activity was
      stable at 37 degrees C in the absence of NADPH. Ascorbic acid, N-acetylcysteine,
      and reduced glutathione significantly increased the yield of hydroxylamine,
      presumably by decreasing further oxidation and covalent binding. Microsomes
      prepared from mice treated with phenobarbital or beta-naphthoflavone catalyzed
      the formation of the hydroxylamine more readily than did microsomes from
      untreated mice. These results demonstrate that cytochrome P-450-mediated
      oxidation of sulfamethoxazole results in the formation of hydroxylamines, which
      can be further oxidized to more reactive intermediates. These metabolites are
      likely involved in the pathogenesis of idiosyncratic reactions.

PMID- 1981738
TI  - Factors affecting the expression of trifluoroacetylated liver microsomal protein
      neoantigens in rats treated with halothane.
AB  - Previous studies have shown that antibodies in the sera of halothane hepatitis
      patients recognize trifluoroacetylated liver microsomal proteins (neoantigens) of
      100 kDa, 76 kDa, 59 kDa, 57 kDa, and 54 kDa. In the present investigation,
      factors that might affect the level of expression of the neoantigens were
      investigated. A study of the time course of neoantigen expression in halothane
      treated rats revealed that the 100 kDa, 76 kDa, 59 kDa, and 57 kDa neoantigens
      were longer-lived than the 54 kDa neoantigen and could be detected in the liver
      up to a week after the administration of halothane. Pretreatment of rats with
      isoniazid, which is known to induce cytochrome P-450 IIE1, appeared to increase
      the expression of each of the neoantigens, whereas inducers of several other
      forms of cytochrome P-450 had either very little effect or decreased the
      expression of several of the neoantigens. Female rats appeared to express some of
      the neoantigens at a higher level than that found in males. Examination of the
      organ distribution of the trifluoroacetylated neoantigens showed that, of the
      tissues examined, only the liver contained appreciable levels of the neoantigens.
      These results indicate that the level of expression and possibly the
      immunogenicity of the trifluoroacetylated liver neoantigens may be influenced by
      their half-lives and the repertoire of cytochrome P-450 present in the liver.

PMID- 1981739
TI  - The metabolic pathways of tianeptine, a new antidepressant, in healthy
      volunteers.
AB  - The metabolism of tianeptine, a novel antidepressant that presents original
      neurochemical properties, was studied after a single oral administration of
      radioisotopically (14C) labeled compound to six healthy male volunteers. After 7
      days, approximately 66% of the dose was eliminated by renal excretion (55% during
      the first 24 hr). Tianeptine is extensively metabolized, and 24 hr after the
      administration, the unchanged molecule contributed in urine for less than 3% of
      the administered dose. Chromatographic and mass spectral studies showed that beta
      oxidation of the amino acid side chain is the major route of biotransformation
      for tianeptine. Three major metabolites, accounting for 29% of the dose, were
      products of beta-oxidation. The metabolite profiles of tianeptine in feces and
      plasma were qualitatively similar to that in urine.

PMID- 1981740
TI  - Pharmacokinetics and protein binding of salicylate metabolites in rats.

PMID- 1981741
TI  - Age-associated alterations in diazepam metabolizing enzyme activities in male and
      female rats.

PMID- 1981742
TI  - Disposition and metabolism of oligodeoxynucleoside methylphosphonate following a
      single i.v. injection in mice.

PMID- 1981743
TI  - Influence of isoniazid, phenobarbital, phenytoin, pregnenolone 16-alpha
      carbonitrile, and beta-naphthoflavone on halothane metabolism and hepatotoxicity.

PMID- 1981744
TI  - Isolation of cDNA fragments hybridizing to rat brain-specific mRNAs.
AB  - A cDNA minilibrary in pUC18 has been generated from 3-month-old rat brains. Two
      hundred clones were randomly selected and sequenced. Comparison with a nucleic
      acid and protein data bank revealed a number of cDNA fragments not homologous to
      any published sequence. Northern blot analyses of some of these clones yielded 5
      brain-specific cDNA fragments. The full-length cDNA for one of these clones has
      been isolated and completely sequenced. It corresponds to an mRNA of about 1,500
      nucleotides, which is present in brain and, to a lesser extent, in heart and
      skeletal muscle. Its expression is developmentally regulated in the rat brain
      from 14-day embryos to 3-month-old adults. A very recent comparison with the EMBL
      nucleotide sequence data bank showed that this mRNA codes for a brain-specific
      snRNP-associated protein.

PMID- 1981745
TI  - Cytochemical and immunocytochemical study on the peroxisomes of rat liver after
      administration of a hypolipidemic drug, MLM-160.
AB  - After administration of a hypolipidemic drug, MLM-160, to male rats, liver
      peroxisomes were studied by biochemical, cytochemical, and immunocytochemical
      methods. The activities of D-amino acid oxidase, glycolate oxidase, and urate
      oxidase increased 2 to 3-fold by the treatment. The increase of the oxidases was
      confirmed by immunoblotting analysis. By light microscopy, immunoreaction for
      catalase was present in the cytoplasmic granules of hepatocytes. The stained
      granules formed some clusters and overlapped each other after MLM-160 treatment.
      However, immunostaining for D-amino acid oxidase and urate oxidase was present in
      discrete fine granules which did not overlap each other. By electron microscopy,
      many peroxisomes showed ring-like extensions and cavitation of the matrix, often
      giving the appearance of a peroxisome-within-a-peroxisome. In many cases, these
      unusual peroxisomes seemed to be interconnected with each other. Within the
      peroxisomes, the catalase was localized in the matrix. Urate oxidase was
      associated with the crystalloid cores. D-amino acid oxidase was localized focally
      in a small part of the matrix where the catalase was mostly negative. In
      conclusion, the administration of MLM-160 to male rats induces some peroxisomal
      oxidases, accompanying the appearance of unusual peroxisomes. The precise
      localization of peroxisomal enzymes suggested that there are subcompartments
      within the liver peroxisomes as shown in rat kidney peroxisomes.

PMID- 1981746
TI  - Induction of glutamine synthetase in periportal hepatocytes by cocultivation with
      a liver epithelial cell line.
AB  - Cocultures of periportal, glutamine synthetase-negative (GS-) hepatocytes with
      endothelial cells of human veins or epithelial cells of rat liver (clone RL-ET
      14) were established for testing whether GS could be induced in the hepatocytes
      by interactions between the different cell types. While GS activity in
      endothelial cells was below detection level that of RL-ET-14 cells decreased from
      62 mU/mg (24 h) to 38 mU/mg (168 h). During cocultivation with endothelial cells
      no change in the low GS activity could be detected. In contrast, when periportal
      hepatocytes were cocultured with RL-ET-14 cells, GS activity of the cocultures
      increased continuously from 26 mU/mg (24 h) to 56 mU/mg during cultivation for
      168 h. Immunocytochemical staining of the cocultures for GS showed that this rise
      of GS activity was associated with an increase of GS level in the periportal
      hepatocytes and a decrease in the RL-ET-14 cells. Correspondingly, cultivation of
      periportal hepatocytes with media conditioned by the RL-ET-14 cells led to an
      increase in GS activity which, however, remained below that of cocultures, while
      conditioned medium of hepatocytes resulted in a decrease of GS activity in pure
      cultures of RL-ET-14 cells. "Separated" cocultures, where hepatocytes and RL-ET
      14 cells reached each other only at the border of a circular area, demonstrated
      that induction of GS was highest in the marginal hepatocytes and lowest in those
      located in the center indicating that besides (a) soluble factor(s) other kinds
      of cell-cell interactions might be responsible for full induction of GS
      expression in periportal hepatocytes.

PMID- 1981747
TI  - Risk factors for adverse drug reactions--epidemiological approaches.
AB  - Age by itself is not an important risk factor for ADRs. Age-related changes are
      the consequence of a number of individual factors, for example morbidity
      associated with polypharmacy, decline in renal or liver function in the elderly,
      hypoalbuminaemia, reduced body weight, etc. The relationship between
      gastrointestinal bleeding and non-steroidal anti-inflammatory drugs can be
      assessed globally in large cohort studies with access to computerized data, but
      complete accuracy requires access to the original patient records. The increase
      in the risk of GI bleeding in users of NSAIDs and aspirin was 50% above that in
      non-users. About a quarter of ADRs in hospitalized patients seem not to arise
      from purely pharmacological mechanisms. They are mainly due to allergic,
      anaphylactoid, or idiosyncratic reactions and to intolerance. In such non
      pharmacological reactions, the time of exposure, reaction time, and even dosage
      may be important factors in identification of the causal drug. The use of
      benzodiazepines can be optimized by taking into account potency, time of action
      and the different syndromes encountered after withdrawal. Following long-term use
      problems of relapse and rebound are being increasingly recognized, in addition to
      organic withdrawal symptoms. In psychiatric patients extrapyramidal disorders due
      to neuroleptics are common. The rates of these ADRs differ markedly between
      various drugs, even after dosages and co-medications are taken into account.
      Epidemiological screening for potentially carcinogenic drugs can only be done in
      large cohorts of patients with pre-recorded full information sets as may be found
      in an HMO (Health Maintenance Organization). The findings of several such studies
      have been published in specialist cancer journals.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1981748
TI  - Comparative study of mifentidine and ranitidine in the short-term treatment of
      duodenal ulcer.
AB  - The efficacy and safety of mifentidine 20 mg at night, a new, potent, long-acting
      H2-receptor antagonist, has been compared with ranitidine 300 mg at night in 60
      patients with acute duodenal ulcer, in a randomized double-blind study. Antacid
      tablets were allowed as additional treatment for pain relief. The treatment
      lasted for 4 weeks. After 4 weeks of treatment the healing rate was similar;
      amongst the patients who completed the treatment, healing was 68% for
      mifentidine, 63% for ranitidine, and on intention-to-treat analysis, healing in
      both groups was 63%. Pain relief and antacid consumption were similar in both
      groups. Clinically significant adverse effects were not detected and any changes
      in laboratory values were minimal, clinically insignificant and reversible.
      Mifentidine appears to be an effective and safe once-a-day treatment for acute
      duodenal ulcer disease.

PMID- 1981749
TI  - Identification of the opioid receptor types mediating beta-endorphin-induced
      alterations in dopamine release in the nucleus accumbens.
AB  - In the present study we used in vivo microdialysis to examine the influence of
      beta-endorphin on dopamine (DA) release in the nucleus accumbens of anesthetized
      rats and to identify the opioid receptor types mediating its effects.
      Microdialysis probes were inserted into the nucleus accumbens and perfusates were
      analysed for DA and its metabolites, dihydroxyphenylacetic acid (DOPAC) and
      homovanillic acid (HVA), using a reversed phase HPLC system with electrochemical
      detection for separation and quantification. Intracerebroventricular (i.c.v.)
      administration of beta-endorphin resulted in a dose-dependent increase in DA and
      its metabolites. Pretreatment with the selective delta-antagonist ICI 174,864
      significantly attenuated the beta-endorphin-induced increase in DA release and
      metabolism whereas pretreatment with the selective mu-antagonist CTOP resulted
      abolition of the beta-endorphin effect. These data demonstrate that the blockade
      of either mu- or delta-opioid receptors is sufficient to antagonize the
      stimulatory effects of beta-endorphin on DA release and metabolism. As such,
      these findings suggest that the concomitant activation of both mu- and delta
      receptors underlies the effects of beta-endorphin on DA release in the nucleus
      accumbens.

PMID- 1981750
TI  - Effects of dopamine D1 and dopamine D2 receptor agonists on coronary and
      peripheral hemodynamics.
AB  - This study evaluated the coronary dopamine receptors by using the dopamine D1
      receptor agonist fenoldopam, dopamine D2 receptor agonist propylbutyldopamine,
      and their selective antagonists SCH23390 and domperidone. Left circumflex
      coronary flow (CF), coronary perfusion pressure at constant flow, left
      ventricular hemodynamics, and total peripheral vascular resistance (TPR) were
      measured in pentobarbital-anesthetized dogs at constant arterial pressures. At
      doses of 200, 500 and 5000 nM, both fenoldopam and propylbutyldopamine induced
      dose-related inotropic effects, as evidenced by maximal dp/dt and cardiac output,
      an increase in CF, decrease in coronary vascular resistance and a decrease in
      TPR. Fenoldopam was more potent in its cardiac and coronary effects while
      propylbutyldopamine was more potent peripherally. On the basis of dosage used,
      the positive inotropic effects of fenoldopam and propylbutyldopamine were much
      weaker than dopamine. After beta-receptor blockade, the inotropic and coronary
      effects of fenoldopam and propylbutyldopamine were extremely attenuated.
      Domperidone could largely antagonize the propylbutyldopamine-induced inotropic
      and coronary effects while SCH23390 showed no significant effect. In addition,
      under our experimental conditions, the fenoldopam- and propylbutyldopamine
      induced decreases in TPR were markedly reduced by SCH23390 and domperidone,
      respectively. The results indicate that the coronary effects of fenoldopam and
      propylbutyldopamine result not from a primary coronary vasodilating action, but
      from vasodilation secondary to positive inotropic effects. Both dopamine D1 and
      dopamine D2 receptors are involved in the peripheral vascular hemodynamics.

PMID- 1981751
TI  - Imidazoline receptors in rat liver cells: a novel receptor or a subtype of alpha
      2-adrenoceptors?
AB  - An imidazoline/guanidine receptor has been characterized in rat liver cells.
      Binding of [3H]idazoxan, a selective benzodioxan antagonist, to imidazoline
      receptor on intact fresh hepatocytes (Bmax = 801 +/- 23 fmol/mg protein, Kd = 11
      +/- 0.8 nM) and to liver membranes (Bmax = 400 +/- 38 fmol/mg protein, Kd = 10 +/
      2 nM) was saturable at 4 degrees C within 3.5 h and at 30 degrees C within 30
      min, respectively. Rat lung membranes had more imidazoline sites (Bmax = 578 +/-
      30 fmol/mg protein, Kd = 14 +/- 1.4 nM) than alpha 2-adrenoceptors (Bmax = 175.0
      +/- 20.0 fmol/mg protein, Kd = 4.8 +/- 2.0 nM). We also screened other tissues
      for imidazoline sites; the ratio of adrenoceptors to total sites labeled with
      [3H]idazoxan displaced by cirazoline was lower in rat lung compared to rat brain
      and human platelets. The imidazoline receptor has common pharmacological
      properties with alpha 2-adrenoceptors, although it is not a subtype of the
      adrenoceptor, since it bound neither the endogenous agonists norepinephrine and
      epinephrine, nor the selective alpha 2-antagonists yohimbine and phentolamine.
      All guanidine type alpha 2-adrenoceptor drugs (e.g. guanbenz, guanoxan) and
      imidazolines (e.g., UK-14,304, naphazoline) competed with high affinity for the
      liver imidazoline receptor. The lack of effect by Gpp(NH)p, a non-hydrolysable
      GTP analogue, on the affinity of guanidine- and imidazoline-type ligands for
      liver imidazoline receptors suggests that the mode of action of these drugs at
      imidazoline receptors is different than at conventional alpha 2-adrenoceptors.
      Ionic changes were considered as a possible mechanism underlying the alpha 2
      adrenoceptor effects in various cells. Opening of K+ channels by alpha 2
      adrenoceptors agonists is a pathway which might be shared by imidazoline-type
      agonists at imidazoline sites. Indeed, 4-aminopyridine, a K+ channel blocker,
      inhibited the specific binding of [3H]idazoxan to liver cells with an IC50 of
      0.34 +/- 0.07 mM a concentration which is effective in blocking K+ channels in
      neuronal cells. Similarly, Cs+ and NH4+ effectively interfered with [3H]idazoxan
      binding, suggesting a possible coupling of imidazoline sites to K+ gating. The
      endogenous ligand clonidine-displacing substance (CDS), which was isolated from
      bovine brain and which binds to alpha 2-adrenoceptors in brain membranes and
      human platelets competed with idazoxan at rat liver imidazoline
      receptors.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1981752
TI  - Non-adrenergic non-cholinergic relaxation mediated by nitric oxide in the canine
      ileocolonic junction.
AB  - The nature of the inhibitory non-adrenergic non-cholinergic (NANC)
      neurotransmitter was studied in circular muscle strips of the canine terminal
      ileum and ileocolonic junction. Nitric oxide (NO) induced tetrodotoxin-resistant
      NANC relaxation, similar to that induced by electrical stimulation or
      acetylcholine (ACh). Incubation with the stereospecific inhibitors of NO
      biosynthesis, NG-monomethyl-L-arginine (L-NMMA) and NG-nitro-L-arginine (L-NNA),
      resulted in an increase of basal tension in the ileocolonic junction which was
      partly reversed by L-arginine but not by D-arginine. Moreover, L-NMMA and L-NNA,
      but not D-NMMA, concentration dependently inhibited the NANC relaxation in
      response to electrical stimulation and ACh, but not that in response to NO or
      nitroglycerin. This inhibitory effect was reversed by L-arginine but not by D
      arginine. Hemoglobin reduced the NANC relaxation in response to electrical
      stimulation, ACh and nitroglycerin, and abolished the responses to NO. Our
      results suggest that NO or a NO releasing substance mediates the NANC relaxation
      in the canine terminal ileum and ileocolonic junction.

PMID- 1981753
TI  - Physical dependence induced in DBA/2J mice by benzodiazepine receptor full
      agonists, but not by the partial agonist Ro 16-6028.
AB  - Continuous administration of triazolam, alprazolam or diazepam for a 7-day period
      by means of minipumps or chronic (17 days) p.o. treatment with alprazolam induced
      clear physical dependence in DBA/2J mice as assessed by precipitation of a
      withdrawal syndrome with an i.v. injection of the benzodiazepine receptor partial
      inverse agonist Ro 15-3505. In contrast, no precipitated withdrawal signs were
      observed following chronic exposure to high doses of the benzodiazepine receptor
      partial agonist Ro 16-6028. The use of minipumps and precipitation with a
      benzodiazepine receptor antagonist permits a simple and rapid evaluation of the
      physical dependence liability of potent compounds acting at the benzodiazepine
      receptor. Furthermore, these results support the hypothesis that benzodiazepine
      receptor partial agonists are less likely to induce physical dependence than full
      agonists.

PMID- 1981754
TI  - [The basic principles of chemical signal transmission in effector cells].

PMID- 1981755
TI  - [Secondary messengers in the hormonal regulation of the functional activity of
      the main and mucoid cells in the stomach].
AB  - The messenger role of Ca+2, cyclic nucleotides and inositol triphosphates in the
      stimulation of pepsinogen and mucous secretion were studied using isolated pig
      [correction of nug] gastric chief cells and guinea pig mucous cells, resp.
      Pepsinogen secretion was stimulated by agents either working at the postreceptor
      adenylate cyclase (AC) level (db-cAMP, forskolin) or after 12-o-tetradecanoyl
      phorbol-13-acetate (TPA) stimulation of protein kinase C (PK C). Similar
      secretory effects were observed with histamine (H), carbachol (C) and
      cholecystokinin (CCK). [Ca-2] in was elevated by C and by CCK, but not by H in
      both types of cells. Like TPA, both C and CCK, but not H, stimulated the Ca+2
      sensitive particulate PK C. H increased the activity of cAMP-dependent PK A.
      PGE2, C and CCK were found to increase inositol-1,4,5-triphosphate content in
      mucous cells. The findings indicate that two pathways of the regulation of
      pepsinogen and mucous secretion (AC-cAMP-PK C and phosphoinositol breakdown
      cascade) can act synergistically.

PMID- 1981756
TI  - [The participation of the hypophyseal-adrenal system in regulating alpha 2
      adrenoreceptor reactivity. The effects of extreme exposures and alpha 2
      adrenoblockaders].
AB  - The simulation of the hypo- and hyperactivity of the hypophysis-adrenocortical
      system induced considerable changes in the reactivity of alpha 2-adrenoceptors,
      as well as in the resistance of the organism to stressful influences. The
      findings support the assumption that the blockade of alpha 2-adrenoceptors is one
      of the key features in the adaptive mechanism of the glycocorticoid hormones
      action.

PMID- 1981757
TI  - [The suppression of neurogenic vascular reactions by a factor released into the
      blood during immobilization stress].
AB  - In isolated segment of the rat tail artery perfused with the animal donor's blood
      the effect of suppression of neurogenic vascular tonus, in immobilization of the
      animal donor, was found in 80% of cases. In 62% of cases, the suppression
      occurred at the beginning of the immobilization and seemed to be due to the
      effect of hypothetical humoral factor on the synapse area. In 38% of cases, the
      suppression started within 30-40 min of the immobilization start and had a
      different cause. The adaptive significance of these responses is discussed.

PMID- 1981758
TI  - [Glucocorticoid control of the mediator process in the brain structures during
      immediate adaptation].
AB  - In male rats with a high and low blood levels of corticosterone, the activity of
      serotonin-, dopamine-, noradrenaline-, glycine, GABA-, and cholinergic processes
      was shown to depend on the glycocorticoid content in the organism and receptor
      binding of 3H-corticosterone in different brain structures. The formation of
      adequate processes of neurotransmitter adaptation to a short-term vibration is
      only possible at a fairly high level of glycocorticoids in the organism.

PMID- 1981759
TI  - Tardive dyskinesia.

PMID- 1981760
TI  - Associations between restriction site polymorphism and enzyme activity variation
      for esterase 6 in Drosophila melanogaster.
AB  - Thirty-five nucleotide polymorphisms were found in a 21.5-kbp region including
      the Est6 locus among 42 isoallelic lines extracted from a single natural
      population of Drosophila melanogaster. The heterozygosity per nucleotide pair was
      estimated to be 0.010 overall, but was lower in sequences hybridizing to
      transcripts than in those not hybridizing to transcripts. Eleven of 36 pairwise
      comparisons among the nine most common polymorphisms showed significant gametic
      disequilibrium. Four of these polymorphisms were also significantly associated
      with the major EST6-F/EST6-S allozyme polymorphism. Significant disequilibrium
      was generally restricted to polymorphisms less than 1-2 kbp apart. Previously
      reported measures of EST6 activity in virgin adult females proved not to be
      significantly associated with any of the six most common nucleotide polymorphisms
      located in the Est6 coding region or the 1.5 kbp immediately 5'. However, the 11
      haplotypes for five of these polymorphisms that lie in the 1.5-kbp 5' region
      could explain about half of the previously reported variation among the lines for
      both EST6 activity and the amount of EST6 protein in virgin adult males. One
      particular polymorphism, for a RsaI site 530 bp 5' of the initiation codon, could
      explain 21% of the male activity variation among lines. This site is embedded in
      a large palindrome and we suggest that sequences including or close to this site
      may be involved in the regulation of EST6 synthesis in the ejaculatory duct of
      the adult male.

PMID- 1981761
TI  - Homology of melanoma-inducing loci in the genus Xiphophorus.
AB  - Several species of the genus Xiphophorus are polymorphic for specific pigment
      patterns. Some of these give rise to malignant melanoma following the appropriate
      crossings. For one of these pattern loci from the playfish Xiphophorus maculatus
      the melanoma-inducing gene has been cloned and found to encode a novel receptor
      tyrosine kinase, designated Xmrk. Using molecular probes from this gene in
      Southern blot analyses on single fish DNA preparations from 600 specimens of
      different populations of various species of the genus Xiphophorus and their
      hybrids, either with or without melanoma-predisposing pattern, it was shown that
      all individuals contain the Xmrk gene as a proto-oncogene. It is located on the
      sex chromosome. All fish that carry a melanoma-predisposing locus which has been
      identified by Mendelian genetics contain an additional copy of Xmrk, closely
      linked to a specific melanophore pattern locus on the sex chromosome. The
      melanoma-inducing loci of the different species and populations are homologous.
      The additional copy of Xmrk obviously arose by a gene-duplication event, thereby
      acquiring the oncogenic potential. The homology of the melanoma-inducing loci
      points to a similar mechanism of tumor suppression in all feral fish populations
      of the different species of the genus Xiphophorus.

PMID- 1981762
TI  - Genetic structure and DNA sequences at junctions involved in the rearrangements
      of Bacillus subtilis strains carrying the trpE26 mutation.
AB  - Studies on the region upstream to ribosomal operon rrnD of Bacillus subtilis led
      to the characterization of two of the four chromosomal junctions involved in the
      rearrangements (a translocation and an inversion) of the strains carrying the
      trpE26 mutation. Genetic analysis, by integrative mapping, showed linkage of rrnD
      to cysB and hisA (both on segment A) in the trpE26-type strains. Physical
      analysis showed that the region upstream to rrnD is now linked to the trpE-ilvA
      chromosome segment as demonstrated by analyzing restriction site-polymorphism
      between 168 and trpE26-type strains. Similar experiments confirmed the previous
      genetic data on linkage in these areas in strains carrying novel rearrangements
      derived from the trpE26-type strains: stable merodiploids and inversions. The
      nucleotide sequence of the area 5' to rrnD in both types of strains (168 and
      trpE26), the region downstream of the citG gene and the region carrying the
      trpE26 mutation (made available to us by D. Henner) provided evidence for the
      molecular basis of the differences in structure, allowed the identification of
      the break points and revealed the presence of a polypurine region upstream to
      rrnD as seen in other systems in B. subtilis. No extensive homology was found
      between pairs of junctions so far sequenced. The models proposed by C.
      Anagnostopoulos for the role of DNA sequences of intrachromosomal homology
      involved in the transfer of the trpE26 mutation and the formation of novel
      arrangements require therefore reevaluation.

PMID- 1981763
TI  - Decreasing gradients of gene conversion on both sides of the initiation site for
      meiotic recombination at the ARG4 locus in yeast.
AB  - We have constructed eight restriction site polymorphisms in the DED81-ARG4 region
      and examined their behavior during meiotic recombination. Tetrad analysis reveals
      decreasing gradients of gene conversion on both sides of the initiation site for
      meiotic recombination at the ARG4 locus, extending on one side into the ARG4
      gene, and on the other side into the adjacent DED81 gene. Gene conversion events
      can extend in both directions from the initiation site as the result of a single
      meiotic event. There is a second gradient of gene conversion in DED81, with high
      levels near the 5' end of the gene and low levels near the middle of the gene.
      The peaks of gene conversion activity for the DED81 and ARG4 gradients map to
      regions where double-strand breaks are found during meiosis. The implications of
      these results for models of meiotic gene conversion are discussed.

PMID- 1981764
TI  - Transformation of chloroplast ribosomal RNA genes in Chlamydomonas: molecular and
      genetic characterization of integration events.
AB  - Transformation of chloroplast ribosomal RNA (rRNA) genes in Chlamydomonas has
      been achieved by the biolistic process using cloned chloroplast DNA fragments
      carrying mutations that confer antibiotic resistance. The sites of exchange
      employed during the integration of the donor DNA into the recipient genome have
      been localized using a combination of antibiotic resistance mutations in the 16S
      and 23S rRNA genes and restriction fragment length polymorphisms that flank these
      genes. Complete or nearly complete replacement of a region of the chloroplast
      genome in the recipient cell by the corresponding sequence from the donor plasmid
      was the most common integration event. Exchange events between the homologous
      donor and recipient sequences occurred preferentially near the vector:insert
      junctions. Insertion of the donor rRNA genes and flanking sequences into one
      inverted repeat of the recipient genome was followed by intramolecular copy
      correction so that both copies of the inverted repeat acquired identical
      sequences. Increased frequencies of rRNA gene transformants were achieved by
      reducing the copy number of the chloroplast genome in the recipient cells and by
      decreasing the heterology between donor and recipient DNA sequences flanking the
      selectable markers. In addition to producing bona fide chloroplast rRNA
      transformants, the biolistic process induced mutants resistant to low levels of
      streptomycin, typical of nuclear mutations in Chlamydomonas.

PMID- 1981765
TI  - Molecular evolution of Drosophila metallothionein genes.
AB  - The metallothionein genes of Drosophila melanogaster, Mtn and Mto, may play an
      important role in heavy metal detoxification. Several different tandem
      duplications of Mtn have been shown to increase cadmium and copper tolerance, as
      well as Mtn expression. In order to investigate the possibility of increased
      selection for duplications of these genes in natural populations exposed to high
      levels of heavy metals, we compared the frequencies of such duplications among
      flies collected from metal-contaminated and non-contaminated orchards in
      Pennsylvania, Tennessee and Georgia. Restriction enzyme analysis was used to
      screen 1666 wild third chromosomes for Mtn duplications and a subset (327) of
      these lines for Mto duplications. The frequency of pooled Mtn duplications found
      ranged from 0% to 20%, and was not significantly higher at the contaminated
      sites. No Mto duplications were identified. Estimates of sequence diversity at
      the Mtn locus among a subsample (92) of the duplication survey were obtained
      using four-cutter analysis. This analysis revealed a low level of polymorphism,
      consistent with both selection at the Mtn locus, and a fairly recent origin for
      the duplications. To further examine this hypothesis, we sequenced an Mtn allele
      of Drosophila simulans and measured the amount of nucleotide sequence divergence
      between D. simulans and its sibling species D. melanogaster. The levels of silent
      nucleotide polymorphism and divergence in the Mtn region were compared with those
      in the Adh region, using the neutrality test of R.R. Hudson, M. Kreitman and M.
      Aguade.

PMID- 1981766
TI  - The effect of L-acetylcarnitine on some reproductive functions in the
      oligoasthenospermic rat.
AB  - The effect of L-acetylcarnitine (LAC) on some parameters of male reproductive
      function was studied on rats made oligoasthenospermic with dibromochloropropane
      (DBCP). DBCP depresses sperm count and motility. After one injection of the drug,
      LAC induces a recovery of both sperm count and motility but after two injections
      it is ineffective. This effect is also shown visually by microscopic examination
      of seminiferous tubules. Among the enzymatic activities evaluated as biochemical
      markers of testicular function both lactate dehydrogenase and NADPH-cytochrome P
      450-reductase increased significantly (P less than 0.05) after treatment with LAC
      in normal rats. LAC also stimulates testosterone production. It is suggested that
      LAC may affect testicular function.

PMID- 1981767
TI  - Effect of Somatostatin on TSH levels in non-toxic sporadic goiter.
AB  - Somatostatin (SS-14; growth hormone-release inhibiting hormone) was infused into
      eight patients with non-toxic sporadic goiter and into eleven normal control
      subjects. Each patient was given 150 microgram(s) of somatostatin as an
      intravenous bolus and 350 microgram(s) by infusion over a period of 60 minutes.
      Somatostatin did not lower the basal TSH levels as compared to the pre-infusion
      levels in this type of goiter, but produced a decrease in the TSH response to TRH
      during and after the infusion.

PMID- 1981768
TI  - Depressed tubular adenoma of the stomach: pathological and immunohistochemical
      features.
AB  - We examined 12 depressed tubular adenomas of the stomach pathologically and
      immunohistochemically in order to clarify the difference between the depressed
      type and the elevated type. Depressed tubular adenomas showed shallow mucosal
      depression and, of the 12, nine were endoscopically diagnosed as early gastric
      cancer. Histologically, the adenoma cells showed dysplasia in varying degree and
      focal adenocarcinoma occurred in two adenomas measuring over 2 cm. The mean
      height of the adenoma glands was 0.63 +/- 0.31 mm in the 12 depressed adenomas
      and 1.32 +/- 0.43 mm in 44 elevated adenomas, while the mean heights of the
      subjacent mucosa were 0.18 +/- 0.19 mm and 1.07 +/- 0.71 mm, respectively. Thus,
      depressed adenomas resulted from paucity of the mucosa subjacent to the adenoma
      glands and the height of the adenomatous glands was half that found in the
      elevated type. Goblet cells, a variety of endocrine cells and lysozyme-containing
      cells were found in nine, nine and eight depressed adenomas, respectively, in
      variable numbers. Hyperplasia of these cells was also detected in depressed
      adenomas showing mild or moderate dysplasia. Immunohistochemical examination
      revealed no difference in the phenotypic expression of adenoma cells as between
      the depressed and the elevated type.

PMID- 1981770
TI  - Local application of somatostatin in the rat ventrolateral brain medulla induces
      apnea.
AB  - Local injections of the tetradecapeptide somatostatin (SOM) into the brain stem
      region were performed in anesthetized and decerebrate rats. SOM administration
      (0.6-1.8 nmol) into the nucleus paragigantocellularis and the nucleus reticularis
      lateralis of the ventrolateral medulla oblongata induced ventilatory depression
      and apnea. The occurrence of apnea was dose dependent and attributed to the
      anesthetic depth, and it was seen within 60-240 s after injection. In
      anesthetized rats the apnea was seen as a termination or a continuous decrease in
      tidal volume while respiratory frequency remained unaltered. SOM-induced apnea
      was caused by depression of central inspiratory drive. SOM injections into the
      dorsal medulla were ineffective in eliciting apnea, although a ventilatory
      depression but no apnea was induced in the awake unanesthetized state. In
      addition to its effect on basal ventilation, SOM administration in the
      ventrolateral medulla resulted in a blunted ventilatory response to hypoxic and
      hypercapnic stimuli in anesthetized rats. We conclude that SOM has potent
      inhibitory effects on respiration that are specifically located in the nucleus
      paragigantocellularis and the nucleus reticularis lateralis.

PMID- 1981769
TI  - Purification of a low-molecular-weight excitatory substance from the inner ears
      of goldfish.
AB  - The neurotransmitter released by the hair cell has not been identified; little is
      known about other neuroactive substances that may be important in hair-cell organ
      function. To identify neuroactive substances in hair cell tissue, we have
      examined substances in extracts of the inner ears of goldfish that can excite
      afferent fibers innervating hair cells. The extracts contain an unidentified low
      molecular-weight (LMW) excitatory substance that is a candidate to be the hair
      cell neurotransmitter. The LMW excitatory substance has been highly purified by a
      sequential combination of (1) treatment with cation-exchange resin; (2) gel
      permeation chromatography; (3) gradient-elution cation-exchange chromatography;
      (4) isocratic-elution cation-exchange chromatography; and (5) high-performance
      anion-exchange chromatography. Based upon its separation behavior in these
      purification steps, the LMW excitatory substance may be a small, zwitterionic
      compound with titratable anionic and cationic groups.

PMID- 1981771
TI  - Molecular analysis of 25 Chinese families with Duchenne/Becker muscular
      dystrophy.
AB  - Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are allelic
      X-linked progressive neuromuscular diseases. We have collected 25 Chinese
      families each with at least one DMD/BMD patient for DNA analysis in the Xp21
      region. Eight genomic probes, 6 within and 2 flanking the DMD gene, and 7
      restriction enzymes were used to detect 9 restriction fragment length
      polymorphisms (RFLPs): C7-EcoRV, J-Bir-BamHI, pERT87-30-BglII, pERT87-15-BamHI,
      pERT87-15-XmnI, pERT87-1-XmnI, XJ1.1-TaqI, XJ5.1-SphI, and 754-PstI. From
      analysis of unrelated subjects, we found that the 4 most informative RFLPs in the
      linkage study were pERT87-15-XmnI, pERT87-1-XmnI, XJ5.1-SphI and J-Bir-BamHI. Two
      flanking markers, C7 and 754, were noninformative in most families. Three
      families (12%) had gene deletion: family M-25 at pERT87-1 to 87-30; M-105 at XJ
      5.1, 1.1, pERT87-1, and 87-15; and M-110 at XJ5.1, 1.1, and pERT87-1 to 87-30.
      Two recombinations were detected: M-10 between C7 and pERT87-15; and M-39 between
      J-Bir and pERT87-15. In the 25 mothers with affected sons, 2 had gene deletion, 1
      was homozygous at all 9 polymorphic loci and the other 22 were heterozygous at
      more than one locus. Twenty-four at-risk female siblings were studied for
      carriership. Nine were classified as at high risk of carriership, 13 at low risk
      of carriership by haplotyping, and the remaining two were uncertain, with one due
      to recombination and the other to maternal homozygous haplotypes. Gene deletion
      and RFLP analysis are very useful in genetic counseling of Chinese DMD/BMD.

PMID- 1981772
TI  - Cutaneous thermal thresholds in normal subjects and diabetic patients without
      symptoms of peripheral neuropathy.
AB  - An automated system operating on the Peltier principle and using a two
      alternative forced-choice testing technique was applied to measure the heat and
      cold thermal thresholds (HT and CT) in 63 normal subjects and 68 diabetic
      patients who had no clinical symptoms of peripheral neuropathy. To compare large
      and small nerve fiber functions, 34 of the diabetic group were also tested for
      vibration perception threshold (VPT) and nerve conduction velocity (NCV). The
      testing algorithm of the devices selected for used, including reference
      temperature and number of turns, was investigated for assessment of variability
      and reliability. The age effect on thermal thresholds was found in the normal
      group (p less than 0.001). There was a significant difference between HT and CT
      in an individual (p less than 0.01). CT was greater than HT in 68% of the
      subjects. The diabetic group had significantly higher thermal thresholds than the
      normal group (HT, 0.30 +/- 0.32 degree C vs 0.10 +/- 0.05 degree C, p less than
      0.005; CT, 0.39 +/- 0.43 degree C vs 0.15 +/- 0.09 degree C, p less than 0.005).
      Thermal thresholds greater than the linear regression estimate for age plus three
      standard errors of estimate were defined as abnormal. The abnormality rate in
      diabetics was 33.8% for HT and 22.1% for CT. Of the 34 patients, 91.1% had
      abnormal results in at least one of the three tests: 47.1% abnormal for HT or CT,
      67.6% for VPT, and 26.4% for NCV. No correlation existed between the thermal
      threshold and VPT (p greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1981773
TI  - Fungemia: analysis of 43 cases.
AB  - This report reviews the cases of 43 patients with 48 episodes of fungemia, and
      examines the clinical significance of fungemia and the results of treatment. All
      episodes were nosocomial infections. Candida albicans (60.4%), Candida
      parapsilosis (16.7%), and Candida tropicals (14.6%) were the most common fungal
      pathogens isolated from blood cultures. Patients with Candida albicans had a
      better survival rate than those with other species (p = 0.011). Polymicrobial
      fungemia was noted in 5 patients (11.6%). Most patients had underlying diseases
      and predisposing factors. Intravascular catheters (100%), broad-spectrum
      antibiotics administration (100%), surgical procedures (46.5%) and total parental
      alimentation (41.9%) were the most common predisposing factors. The clinical
      manifestations were not characteristic and consisted of nonspecific signs of
      sepsis. The overall mortality rate was 79%. We did not find any improvement in
      the mortality rate of our patients treated with amphotericin B. Early
      recognization, immediate removal of predisposing factors, and correction of
      underlying conditions is most important for patients with fungemia. We also
      suggest that fungal infection should be considered early when a febrile patient
      at high risk dose not improve with broad-spectrum antibacterial therapy.

PMID- 1981775
TI  - Isokinetic study of muscle strength in osteoarthritic knees of females.
AB  - The present investigation was aimed at assessing the difference in peak torque
      between normal and osteoarthritic (OA) knees in females. Fifty-five female
      osteoarthritic patients with 85 osteoarthritic knees were studied. Thirty-three
      normal females of similar age were also collected as a control group. The muscle
      torque of the knee flexor and extensor was assessed by a Cybex II dynamometer.
      The speed of isokinetic contraction was set at 30 RPM, 5 RPM, and 0 RPM. The
      muscle torque of the affected knee in patients with unilateral osteoarthritis was
      found to be significantly greater than that of those with bilateral
      osteoarthritis (p less than 0.05). The peak torque of OA patients at the faster
      speed (30 RPM) showed significant deterioration with age. Compared with the value
      for controls, the deficit of peak torque in geriatric patients was significant (p
      less than 0.05), especially at the faster speed (30 RPM). The decrease in
      extensor torque in OA knees tended to be greater than that of flexor torque,
      especially in patients less than 51 years of age at 5 RPM and 0 RPM. Age,
      duration of illness and the grading of X-ray change accounted for isokinetic
      torque differences in osteoarthritic knees.

PMID- 1981774
TI  - Clinical observations and virological study of aseptic meningitis in the
      Kaohsiung area.
AB  - During 1988, an endemic outbreak of aseptic meningitis was noted in the Kaohsiung
      area. Throughout the year, a total of 89 cases were identified by cerebrospinal
      fluid (CSF) examination at the Pediatric Department of Kaohsiung Medical College.
      The peak incidence was from June to October. Scattered cases still occurred
      during November and December. The male to female ratio was 1.7:1 and the age
      distribution ranged from 1 month to 15 years old. Two peaks of age distribution
      were observed; one in infancy and the other in the 4-7 year old age group. Most
      of them exhibited fever (94.4%), headache (68.9%), and vomiting (68.5%). Other
      associated symptoms and signs included neck stiffness, sore throat, cough,
      Brudzinski's sign, abdominal pain, seizure, dizziness, rhinorrhea, diarrhea,
      Kernig's sign, skin rash, hyperemic conjunctiva, apnea, and oral ulcers. Most of
      them had CSF white blood cell (WBC) counts less than 1000/mm3, normal or mild
      elevated protein, and normal CSF/plasma sugar ratio. Three patients were found to
      have a virus in their CSF without pleocytosis. Virus isolations from CSF throat
      swabs and/or rectal swabs were performed in 65 patients, half of them (35/65,
      53.8%) had positive results including echovirus type 9 (sixteen), echovirus type
      30 (eighteen), and adenovirus type 3 (one). Echovirus type 9 was predominant
      during July and August whereas echovirus type 30 became predominant after
      September. All patients recovered spontaneously without any sequelae.

PMID- 1981776
TI  - Chronic intravascular hemolysis after valvular surgery.
AB  - The Phenomenon of intravascular hemolysis following cardiac valvular surgery was
      studied among 156 randomly selected patients. There were 76 men and 80 women,
      varying in ages between 15 and 71 years, with a mean age of 48.3 years. The time
      interval between the study and the operations ranged from 2 to 163 months with a
      mean of 41.1 months. The prosthetic valve was used in 129 patients; the xenograft
      tissue valve in 26 and the mechanical valve in 103. Subclinical hemolysis
      occurred in 68.9% of the 129 patients who had one or more prosthetic valve
      implants and in 14.8% of the 27 patients who underwent plastic repair of the
      mitral valve. Compared among the groups with different valve prosthesis,
      hemolysis could be detected in 81.6% of the patients with a mechanical prosthetic
      valve and in 23.1% of those with a bioprosthetic tissue valve (p less than 0.05).
      Twelve patients who had a valve prosthesis were documented to have symptomatic
      gallstones with an incidence of 9.3%. Among them, only 2 patients had biliary
      colic and required cholecystectomy to relieve the associated symptom. Anemia,
      secondary to the hemolysis, occurred in 3.8% of those with a xenograft tissue
      valve and 8.8% of those with a mechanical valve (p less than 0.05). None of them
      needed a blood transfusion. None had related renal impairment. In conclusion, the
      mechanical valve prosthesis has a higher incidence of hemolysis than the
      xenograft valve. Though the mechanical valve prosthesis has its own merits, the
      xenograft tissue prosthesis is superior in this respect.

PMID- 1981777
TI  - An autopsy case of Reye's syndrome associated with acute pancreatitis, acute
      renal failure and disseminated intravascular coagulopathy.
AB  - A three-and-a-half-year-old boy was transferred to our hospital under the
      impression of Reye's syndrome. The laboratory data showed hypoglycemia,
      hyperammonemia and elevated serum transaminases. A remarkable high serum amylase
      level of 2,223 IU/L and CAm/CCr of 36% was noted. A blood urea nitrogen level of
      143 mg/dl was found on the third day and a creatinine level of 8.7 mg/dl on the
      fourth day. Disseminated intravascular coagulopathy (DIC) and systemic candidal
      infection complicated his final course. He died after intensive treatment for
      eleven days. Hemorrhagic pancreatitis and fatty change of the liver were noted at
      autopsy. Disseminated candidal invasion was noted within the kidneys, cerebrum,
      and lungs. Tonsillar herniation, systemic candidiasis and bronchopneumonia were
      believed to be the causes of his death. It is extremely rare for all three
      complications, acute pancreatitis, acute renal failure and DIC, to occur in
      Reye's syndrome at the e time.

PMID- 1981778
TI  - Delayed erythropoiesis after major ABO-incompatible bone marrow transplantation:
      report of a case.
AB  - Major ABO-incompatible bone marrow transplantation (BMT) may be associated with
      delayed erythropoiesis. A 38-year-old man (blood group O) with chronic
      myelogenous leukemia received a BMT from his histocompatibility antigen (HLA)
      identical brother (blood group A). The pre-BMT anti-A titer of the patient was
      1:4. The harvested marrow was depleted of RBC by 6% hydroxyethyl starch
      sedimentation and Ficoll-Hypaque gradient centrifugation. No acute hemolysis
      occurred after marrow infusion. Myeloid and megakaryocytic series engrafted
      promptly. However, delayed erythropoiesis up to day 266 was found. Prolonged
      presence of anti-A antibody was noted for more than 250 days after BMT, although
      the peak titer was only 1:8. After the reconstitution of bone marrow, the
      erythroid series was confirmed as donor origin (RBC cell typing A). It is
      proposed that the prolonged presence of anti-A antibody probably produced from
      the residual host B lymphocytes, would destroy the regenerating erythroid
      precursors. Also, use of cyclosporin A may be associated with higher rates of
      prolonged production of anti-A/B antibodies and the subsequent delayed
      erythropoiesis.

PMID- 1981779
TI  - Staphylococcus aureus endocarditis in drug addicts: report of 2 cases.
AB  - Two young men presented with prolonged hectic fever and chills followed by chest
      pain, dyspnea and hemoptysis. The chest films revealed multiple lung infiltrates,
      and blood cultures yielded Staphylococcus aureus. Echocardiographic examination
      confirmed the diagnosis of tricuspid valve endocarditis. Multiple punctate
      lesions in the bilateral inguinal areas and dragon tattoos over the forechest
      gave rise to the suspicion of drug abuse. After prolonged antimicrobial therapy,
      bacteremia was eliminated, and elective vegetectomy and valvuloplasty were
      performed on one of the patients. The other one suffered recurrent episodes of
      pulmonary embolism. Disappearance of the large vegetation was disclosed by
      echocardiography. Both of them eventually regained their health with the
      abstinence of drugs. This report illustrates two typical cases of infective
      endocarditis in drug addicts.

PMID- 1981780
TI  - Eosinophilic gastroenteritis with eosinophilic ascites: report of a case.
AB  - Eosinophilic gastroenteritis is a relatively uncommon disease of unknown
      etiology. Eosinophilic ascites resulting from significant serosal involvement is
      the rarest clinical subtype. The case reported here is of a 30-year-old male
      presenting with abdominal pain, diarrhea, and ascites. His personal history
      included childhood asthma, allergic rhinitis, and recurrent urticaria. The
      clinical picture was characterized by peripheral eosinophilia and eosinophilic
      infiltrates of the stomach and small bowel. Computed tomogram (CT) of the abdomen
      showed generalized thickening of the gastric and small bowel wall. Paracentesis
      revealed exudative ascites rich in eosinophils. The patient experienced an
      impressive response to steroid therapy.

PMID- 1981781
TI  - Protein synthesis in rat intestine in vitro: the acute effect of ethanol.
AB  - We studied the rate of 3H-leucine incorporation and the acute effect of ethanol
      on rat jejunum employing a newly-developed method originally for determining
      rapid solute uptake in vitro. 3H-leucine incorporation was linear up to 12 min
      and significantly inhibited by 10 microM of cycloheximide, a specific inhibitor
      for protein synthesis. The inhibition was 86% at 100 microM indicating that the
      rate of 3H-leucine incorporation was a good index for protein synthetic activity
      in the intestinal cells. Incorporation was not changed significantly by 8%
      dilution (with water) but was inhibited by 8% ethanol to less than 1/4 of the
      control level. Lower concentrations of ethanol had no consistent effects. The
      action of ethanol was rapid, independent of the precursor level, and was not
      readily reversible. Although the nature of ethanol's action was not clear,
      sucrose, in a dose-dependent manner, also significantly inhibited incorporation
      rapidly, indicated that the action of media hyperosmolality could not be
      eliminated as part of the cause of inhibition induced by ethanol.

PMID- 1981782
TI  - Neonatal hepatic hemangioendothelioma identified by real-time ultrasound: report
      of a case.
AB  - Sonographic findings emphasizing vascular imaging in the identification of a
      resectable huge hepatic hemangioendothelioma in a 1-day-old neonate are reported.
      The prominent sonographic features consisted of dilated hepatic veins, enlarged
      celiac trunk and hepatic artery, indicating arteriovenous shunting, in addition
      to the complex echo pattern of the mass itself. Moreover, sonographic
      visualization of marked caliber discrepancy between hepatic and splenic arteries
      at their origin from the celiac trunk readily provided another subjective
      evidence of hepatic artery dilatation, further reflecting the hypervascularity of
      this hepatic mass. Hence meticulous ultrasonic study of such hepatic masses with
      special attention to their enlarged feeding and draining vessels can provide a
      simple and noninvasive approach for early recognition of this vascular hepatic
      tumor in the immediate newborn period.

PMID- 1981783
TI  - [Drug interaction between digoxin and bisacodyl].
AB  - Digoxin is one of the inotropic agents commonly used to improve cardiac
      performance in patients with congestive heart failure and to control ventricular
      response in atrial fibrillation and other supraventricular tachycardias.
      Bisacodyl (dulcolax), a stimulant laxative, is also commonly prescribed to
      prevent straining at stool or constipation in these patients. Therapeutic
      monitoring of digoxin is helpful in the evaluation of clinical response and
      intoxication of digoxin. For the convenience of serum level measurement, digoxin
      is usually administered at night before sleep to allow ample time for tissue
      distribution and then blood sampling the next morning. Concomitant use of these
      drugs may increase the likelihood of drug interaction. Eleven healthy volunteers,
      aged 22-26, were studied within 35 days accordingly in four phases. The serum
      digoxin concentration (SDC) in phase 2 (digoxin and bisacodyl together) showed a
      significant decrease as compared with phase 1 (digoxin alone) (0.58 +/- 0.03 vs.
      0.66 +/- 0.03 ng/ml, M +/- SE, p less than 0.05). The percentage of SDC changes
      was down to -11.7 +/- 5.4%. Phase 4 (digoxin taken 2 hours before bisacodyl)
      showed an increase in SDC in comparison with phase 3 (digoxin alone) but was not
      statistically significant (0.65 +/- 0.03 vs. 0.62 +/- 0.03 ng/ml, M +/- SE, p
      greater than 0.05). The average frequency of diarrhea was 3.5 times in the first
      day of phase 2 and 2.7 times in the first day of phase 4. We conclude that in
      volunteers bisacodyl interacts with digoxin resulting in reduction of the SDC.
      Interference of the absorption is the most likely mechanism.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1981784
TI  - [Microalbuminuria in insulin-dependent diabetes mellitus: a comparison of
      specimen collection, analytic methods and relationship with glycemic control and
      blood pressure].
AB  - The excretion of small quantities of urinary albumin (microalbuminuria = urinary
      albumin excretion rate, UAER = 20-200 micrograms/min) may predict renal function
      in both insulin-dependent and noninsulin-dependent diabetes. We compared
      radioimmunoassay with the immunoturbidimetric method to detect early increases in
      urine albumin concentration. More problems have been encountered in deciding
      which method of collecting urine best differentiate between early onset diabetic
      nephropathy and normality. Random urine samples collected at clinics are
      convenient but show wide variations in concentration and the effects of exercise.
      Such variations may be overcome by using a rest period and correcting for urine
      creatinine concentration. We studied 21 IDDM patients (12 female, 9 male), aged
      13-33 years old (mean 21) and 11 nondiabetics (6 female, 5 male), aged 15-30
      years old (mean 23). All gave negative results on testing with Albustix at clinic
      visits. All subjects passed urine immediately after they got up in the morning.
      The results disclosed: (1) The correlation coefficient of albumin excretion
      (micrograms/ml) in the urine collected overnight with that collected over 24
      hours was good (r = 0.89, p less than 0.001). (2) When the albumin excretion rate
      of the urine collected overnight was expressed as microgram albumin/mg
      creatinine, the correlation was also as good as the 24-hr urine albumin excretion
      (microgram albumin/mg creatinine) (r = 0.87, p less than 0.001). (3) The results
      of our study support the use of urine samples collected overnight, corrected for
      creatinine, to estimate microalbuminuria.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1981785
TI  - [Fournier's gangrene: report of 3 cases].
AB  - Fournier's gangrene is defined classically as a fulminant, rapidly spreading
      infection of the scrotum that also involves the perineum, penis and abdominal
      wall. The pathologic findings are described as synergistic gangrene secondary to
      a polymicrobial flora with a poorly defined portal of entry. We report 3 cases of
      Fournier's gangrene. Case 1 was a 67 years old who was admitted with the chief
      complaint of scrotal swelling and necrosis. Case 2 was a 59 years old who was
      admitted with the problem of scrotal swelling and pain, he had sought other
      medical help without success, and was then transferred to our hospital. Case 3
      was a 62 years old who was admitted with the chief complaint of scrotal swelling
      and pain for 2 days. These 3 patients were all found to have diabetes mellitus.
      All 3 patients required aggressive surgical debridement, broad-spectrum
      antibiotics and adjunctive measures. Blood cultures were usually negative and pus
      cultures were typically aerobic gram-negative rods and gram-positive cocci and
      anaerobic bacteria of various types, especially Bacteroids fragilis. Our pus
      cultures revealed Escherichia coli and Staphylococcus aureus in Case 1,
      Enterobacter cloacae in Case 2 and E. coli, B. fragilis and Pseudomonas
      aeruginosa in Case 3. This disease is no longer a disease of young men. After
      1945, the average age in 119 reported cases was 51.3 years and the average age of
      our cases was 62.7 years. Before the era of antibiotics, scrotal gangrene was not
      a rarity. In these modern times, in spite of seeking medical attention early,
      patients still developed scrotal gangrene and the mortality rate is
      high.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1981786
TI  - [Penile revascularization: report of 4 cases].
AB  - From February to June in 1989, 4 patients consulted our ward with the complaint
      of impotence. After each patient's history and physical examination were taken, a
      series of tests were administered which included hepatic and renal function,
      blood sugar, cholesterol, triglyceride, testosterone, prolactin level, nocturnal
      penile tumescence (NPT), duplex sonography, cavernosography, and internal
      pudendal arteriography. The results of these tests suggested vasculogenic
      impotence and penile revascularization was attempted. In 2 patients the Michal-II
      method was used. The second patient was treated with the Virag-V method. In the
      fourth patient, the Michal-II method was combined with the administration of the
      Virag-V method. After 6 months of follow-up, objective tests such as NPT and a
      Duplex scanning examination showed moderate improvement in the patients who
      received the Virag-V method, alone or in combination with the Michal-II method.
      Subjectively, all the patients except the one who received just the Virag-V
      method, felt improvement in erection angle, penetration, and satisfaction. We
      conclude that penile revascularization may be a more noninvasive, physiological
      alternative to penile prosthesis for some cases of vasculogenic impotence.

PMID- 1981787
TI  - [Cavernous hemangioma of the heart: report of a case].
AB  - Cavernous hemangioma of the heart is a very rare disease. A 57-year-old male
      patient was admitted due to frequent onset of dull chest pain, which had been
      occurring for about 1 year. The pain was not related to exercise and was not
      relieved with nitroglycerin. On echocardiographic examination, a tumor was shown
      in the outflow tract of the right ventricle and was confirmed with computer
      tomography. He underwent open heart surgery for resection of the tumor. After a
      median sternotomy and opening of the pericardial cavity, a reddish-brown-colored
      tumor, 3 cm in diameter, was found protruding from the epicardial layer of the
      right ventricular outflow tract. The tumor involved all layers of the ventricle
      and could be resected only with the help of the cardiopulmonary bypass technique.
      The defect in the right ventricle was repaired with a woven dacron patch. The
      patient recovered without incident after the operation, and experienced no chest
      pain during 7 months of follow-up. Histology showed it to be a cavernous
      hemangioma.

PMID- 1981788
TI  - Some neuronal properties of PC12 cells differentiated by the K-ras oncogene.
AB  - When infected with a virus containing the Kirsten-ras oncogene, rat
      phaeochromocytoma or PC12 cells elaborated neurites and ceased mitosis, that is,
      they underwent neuronal differentiation. Such differentiated cells could be
      replaced and maintained up to 20 weeks in vitro without the need of an exogenous,
      continuous supply of nerve growth factor (NGF). The neurites of K-ras infected
      PC12 cells, filled with microtubules and actin which was concentrated within the
      growth cones, resembled those of primary neurons in vitro. As in the NGF-primed
      PC12 cells, two types of secretory vesicles were present in the K-ras-infected
      PC12 neurites: large (100 nm), dense core granules, and small (45 nm), clear
      vesicles. Compared to naive PC12 cells, K-ras infected PC12 cells had (a) higher
      activities of acetylcholinesterase and choline acetyltransferase, two enzymes
      involved in acetylcholine metabolism; (b) enhanced activity of tyrosine
      hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis; (c) a
      higher, evoked norepinephrine release; and (d) similar levels of sodium-dependent
      uptake of both choline and norepinephrine. Although the total content of
      catecholamines in K-ras-differentiated PC12 cells was less than that of naive
      cells, both norepinephrine and dopamine were present in substantial amounts and
      norepinephrine was released after stimulation. According to their enzymatic
      activity, these cells can also synthesize acetylcholine and thus have potential
      as donors for the intracerebral replacement of either catecholaminergic or
      cholinergic neurotransmitters.

PMID- 1981790
TI  - [Studies on the contractile mechanism of isolated gastric smooth muscle cells of
      guinea pig--investigation of the histamine receptor].
AB  - Investigation about the histamine receptors of gastric smooth muscle cells was
      done using isolated gastric smooth muscle cells of guinea pig. Isolated gastric
      smooth muscle cells were prepared from the stomach of guinea pig by percoll
      density gradient centrifugation after enzymatic digestion with collagenase and
      dyspase. Contraction of the cells was determined by image of phase-contrast
      microscopy and digitizer and expressed as the mean per cent of control in cell
      axis length. The concentration of intracellular Ca2+ ([Ca2+]i) was measured with
      the calcium-sensitive dye fura-2. Tested drugs were added to the incubation
      medium containing 2 mM CaCl2. Both contractile response and [Ca2+]i increased
      following histamine stimulation in a dose-dependent manner from 10(-7) to 10(-4)
      M, and those peaks were obtained in application of 10(-4) M pyridylethylamine, a
      H1 receptor agonist, made an increase in [Ca2+]i as much as 10(-4) M histamine.
      But 10(-4) M dymaprit, a H2 receptor agonist, made only small increase in
      [Ca2+]i, whose value was similar to that in application of only 2 mM CaCl2. 10(
      4) M pyrilamine, a H1 receptor antagonist, inhibited the response to 10(-4) M
      histamine, and the value was similar to that in application of only 2 mM CaCl2.
      Cimetidine, a H2 receptor antagonist, did not inhibit the response to 10(-4) M
      histamine stimulation at all. From those results it is concluded that the action
      of histamine to the gastric smooth muscle cells of guinea pig may be mediated
      through H1 receptor, but not through H2 receptor.

PMID- 1981789
TI  - Cytotoxicity of equinatoxin II from the sea anemone Actinia equina involves ion
      channel formation and an increase in intracellular calcium activity.
AB  - Equinatoxin II is a 20-kDa basic protein isolated from the sea anemone Actinia
      equina. The aim of our work was to investigate the primary molecular basis for
      the cytotoxic effects of equinatoxin II in two model systems: single bovine
      lactotrophs and planar lipid bilayers. Previous work has shown that equinatoxin
      II produces rapid changes in cell morphology, which are dependent on external
      calcium. It has also been reported that addition of equinatoxin II increases
      membrane electrical conductance, which suggests that the cytotoxic action of
      equinatoxin II involves an increase in the permeability of membranes to Ca2+.
      Extensive changes in cytosolic Ca2+ activity are thought to invoke irreversible
      changes in cell physiology and morphology. In this paper, we show that
      morphological changes brought about by equinatoxin II in bovine lactotrophs are
      associated with a rapid rise in cytosolic Ca2+ activity, monitored with a fura-2
      video imaging apparatus. Moreover, incorporation of equinatoxin II into planar
      lipid bilayers produces Ca2+ permeable ion channels. This suggests that the mode
      of equinatoxin II cytotoxicity involves the formation of cation (Ca2+) permeable
      channels in cell membranes.

PMID- 1981791
TI  - [Effects of H2-receptor antagonist on gastrin and somatostatin secretion of rat
      stomach].
AB  - To investigate the effects of 14 days administration of H2-receptor antagonist
      (famotidine) on gastric gastrin and somatostatin secretion, bombesin and glucagon
      were perfused in the isolated pancreas-duodenum deprived rat stomach. Then serum
      gastrin concentration, gastric mucosal gastrin and somatostatin content, and
      gastric mucosal G-cell and D-cell numbers were examined. The 14 days
      administration of famotidine caused the significant increase of basal gastrin
      secretion, antral G-cell hyperplasia, high gastrin sensitivity to the stimulation
      by bombesin, and the low somatostatin sensitivity to the stimulation by glucagon.
      These facts would suggest that 14 days famotidine administration disturbed not
      only gastrin secretion but also somatostatin secretion. These results may
      contribute, at least in part, to the high recurrence of ulcers after withdrawal
      of H2-receptor antagonists.

PMID- 1981792
TI  - Further evidence for abnormal hindquarter tone in spontaneously hypertensive
      rats.
AB  - In spontaneously hypertensive rats (SHR) and normotensive control rats (NCR),
      hindquarter flow was observed in the conscious state with an electromagnetic flow
      probe chronically implanted around the terminal aorta. Arterial pressure was
      recorded with an indwelling catheter in the common carotid. When arginine
      vasopressin was infused intravenously at a rate of 12.5 ng/(kg.min), the increase
      in hindquarter resistance, calculated as arterial pressure divided by hindquarter
      flow, was significantly (p less than 0.005) augmented after ganglionic blockade
      with hexamethonium in SHR but not in NCR. This is explicable by assuming a tonic
      sympathetic vasoconstrictor activity in the hindquarters of SHR, reflexive
      inhibition of which partially offsets vasoconstrictor effect of infused
      vasopressin.

PMID- 1981793
TI  - Inhibition of proliferative responses and interleukin 2 productions by
      salazosulfapyridine and its metabolites.
AB  - Mixed lymphocytes reactions (MLR) and concanavalin A (Con A)- or
      phytohemagglutinin (PHA)-stimulated proliferative responses were dose-dependently
      inhibited by salazosulfapyridine (SASP) and cyclosporin A (CsA) in the
      concentration ranges of 1 x 10(-5) -5 x 10(-4) M and 10-1000 ng/ml, respectively.
      Such a significant inhibition was not observed with metabolites of SASP,
      sulfapyridine (SP) and 5-aminosalicylic acid (5-ASA). In addition, SASP and CsA
      inhibited the production of interleukin 2 (IL-2) from splenocytes in these
      experiments. The inhibitory effect of CsA on IL-2 production practically
      correlated with that on proliferative responses, whereas SASP showed a less
      marked inhibitory effect on IL-2 production than on proliferative responses.
      Neither SP nor 5-ASA inhibited the IL-2 production. In the Con A-induced
      proliferative response, SASP showed a full inhibition even when added after 4-8
      hr of culture, but CsA did not. The splenocytes that were pulsed with Con A for 4
      hr could proliferate in response to Con A-supernatant or purified IL-2. CsA
      exhibited the inhibitory activity only when present during the time of Con A
      pulsing, while SASP acted on the subsequent stage of the response, exerting its
      inhibitory effect. These findings suggest that SASP down-regulates the immune
      response by a mechanism apparently distinct from that of CsA.

PMID- 1981794
TI  - Selective and competitive histamine H2-receptor blocking effect of famotidine on
      the blood pressure response in dogs and the acid secretory response in rats.
AB  - Famotidine has been already demonstrated to be a competitive H2-receptor
      antagonist in the stomachs of dogs and cats. The present experiments were carried
      out to examine the effects of famotidine on changes in blood pressure induced by
      dimaprit and several other agonists in vagotomized, anesthetized dogs and on
      changes in gastric acid secretion induced by histamine in stomach-perfused,
      anesthetized rats. Famotidine caused a parallel displacement of the dimaprit dose
      response curve to the right with a DR10 value of 0.059 mumols/kg, indicating that
      famotidine is 166 times more potent than cimetidine in vascular H2-blocking
      activity. On the contrary, famotidine did not affect the depressor responses to 2
      pyridylethylamine and histamine that were antagonized by mepyramine. The
      histamine dose-response curve was displaced to the right more markedly after
      simultaneous administration of mepyramine and famotidine than after mepyramine
      alone. The effects of methacholine, phenylephrine and isoproterenol on blood
      pressure were not influenced by famotidine in doses up to 720 nmol/kg. In rats,
      famotidine also caused a parallel displacement of the acid dose-response curve to
      histamine to the right with a DR3 value of 24 mumols/kg/hr in stomach-perfused
      rats anesthetized with pentobarbital, exhibiting a potency 108 times greater than
      that of cimetidine. Analysis of the acid dose-response curve with the Edie
      Hofstee transformation showed that famotidine, like cimetidine, was a competitive
      H2-receptor antagonist.

PMID- 1981795
TI  - A method for determining urinary enzyme activities as nephrotoxic indicators in
      rats.
AB  - A simple, useful method was developed for detecting drug nephrotoxicity in rats.
      Rat urine excreted by stimulation of the sacral part of the back was collected in
      a beaker, and enzymes in 0.2 ml of the urine were partially purified by
      centrifugal ultrafiltration using an Amicon MPS-1 kit. Activities of N-acetyl
      beta-D-glucosaminidase (NAG), alanine aminopeptidase (AAP), gamma
      glutamyltranspeptidase (gamma GTP) and lactate dehydrogenase (LDH), and the
      protein concentration of the enzyme preparation suspended in phosphate-buffered
      saline were represented as creatinine ratios. A marked increase in these enzyme
      activities and protein concentration were observed in rats with kidneys damaged
      by treatment with cephaloridine, HgCl2, cisplatin or gentamicin. The patterns of
      increase of these indicators differed with the drug, but in general, LDH showed
      the highest response and NAG, the longest lasting one. These data agreed with the
      results reported by other researchers using dialyzed 24-hr urine. Thus, we
      concluded that this method is an efficient one for determining drug
      nephrotoxicity in rats.

PMID- 1981796
TI  - [Childbirth in Zurich is performed safely and intimately].

PMID- 1981797
TI  - [Perinatology meeting in Jyvaskyla city].

PMID- 1981798
TI  - [Glad to be a woman].

PMID- 1981799
TI  - [The family viewpoint main topic at Midwifery Meeting].

PMID- 1981800
TI  - [Polyarteritis nodosa. Considerations on a clinical case].
AB  - A case of polyarteritis nodosa is reported. The patient, a 56-year-old white
      woman, had cutaneous nodules, ulcers and livedo reticularis over the limbs.
      Abdominal angiography revealed the presence of microaneurysms. Hypertension,
      rheumatic heart disease (under anticoagulation therapy) and diabetes mellitus,
      were also detected. The controversial attempt in distinguishing between systemic
      and cutaneous polyarteritis is emphasized, and the influence of warfarin on skin
      lesions morphology is discussed.

PMID- 1981801
TI  - Plasmid-encoded production of coli surface-associated antigen 1 (CS1) in a strain
      of Escherichia coli serotype O139.H28.
AB  - Production of coli surface-associated antigen 1 (CS1) by Escherichia coli strain
      E24377 of serotype O139.H28 was controlled by a plasmid that also encoded heat
      stable and heat labile enterotoxins and CS3. The presence of a regulatory
      sequence was detected on this plasmid by hybridization with the cfaD gene that
      regulates expression of colonization factor antigen I fimbriae and is at least
      96% homologous with the rns sequence controlling production of CS1 or CS2
      fimbriae by strains of serotype O6.H16 of appropriate biotype. A separate
      plasmid, pDEP20, carrying the structural genes for CS1 synthesis was identified
      and transformed into E. coli strain HB101 or a derivative of strain E24377
      without large plasmids. Transformants carrying pDEP20 did not produce CS1
      fimbrial antigen, but antigen expression was obtained when a cloned cfaD gene or
      a wild-type plasmid carrying the rns sequence was introduced. Transposon
      mutagenesis with Tn1000 identified a 3.7 kbp region of pDEP20 essential for
      production of CS1 fimbriae. Genes encoding production of CS1 fimbriae were cloned
      on a 9.9 kbp BamHI fragment and were expressed in the presence of the cfaD
      sequence. A strain producing both CS1 and CS2 antigens was constructed by
      introduction of the cloned cfaD gene into a strain of serotype O6.H16 biotype C
      carrying plasmid pDEP20.

PMID- 1981802
TI  - Geographically distinct isolates of Mycobacterium leprae exhibit no genotypic
      diversity by restriction fragment-length polymorphism analysis.
AB  - Differentiation of microorganisms for taxonomic purposes is based primarily on
      phenotypic characteristics, which are the direct or cumulative result of gene
      expression. Since expression of phenotypic characteristics usually relies on in
      vitro growth of a microorganism, non-cultivable organisms, such as Mycobacterium
      leprae, present major problems for the identification of potential variants based
      on phenotypic similarities or differences between individual isolates. We have
      employed the use of restriction fragment-length polymorphism (RFLP) analysis of
      chromosomal DNA of M. leprae isolates, including human isolates from
      geographically distinct regions of the world and isolates from a Sooty Mangabey
      monkey and an armadillo, to assess the relatedness among these isolates.
      Restriction endonuclease (EcoRI, BstEII, PstI, and PvuI) digests of chromosomal
      DNA were analysed using DNA probes encoding all or part of the 12 kD, 18 kD, 28
      kD, 65 kD and 70 kD proteins of M. leprae as well as a probe containing an M.
      leprae-specific sequence repeated up to 20 times in the M. leprae chromosome.
      Comparison of the resulting autoradiographs showed that the RFLP patterns were
      all identical, indicating that these isolates contained no polymorphism with
      respect to the restriction endonuclease sites analysed. In addition, RFLP
      patterns of two separate human M. leprae isolates remained unchanged after three
      cycles of experimental infection in the armadillo model. These results indicated
      that the M. leprae isolates tested in this study were indistinguishable at the
      genotypic level, strongly suggesting homogeneity among members of this species.

PMID- 1981803
TI  - Functional importance of the Escherichia coli ribosomal RNA leader box A sequence
      for post-transcriptional events.
AB  - To shed more light on the controversial findings concerning the functional
      participation of the highly conserved nut-like leader box A sequence element in
      ribosomal RNA transcription antitermination we have carried out a mutational
      study. We have substituted the box A and combined this mutation with several
      deletions comprising the rRNA leader elements box B, box C and the tL region. The
      mutations are located within the genuine rrnB operon cloned on multicopy
      plasmids. We determined the effects of the mutations on cell growth, rRNA
      accumulation and ribosomal subunit stoichiometry. Cells transformed with the
      mutated plasmids were affected in their growth rate, and showed a surprising
      deficiency of the promoter-proximal 16S compared to the 23S RNA, indicative of a
      post-transcriptional degradation event. Accordingly, we could demonstrate a
      reduced amount of free 30S relative to 50S ribosomal subunits in exponentially
      growing cells. Similar stoichiometric aberrations in the ribosome pool were
      detected in conditionally Nus factor-defective strains. The results show that the
      leader box A sequence within rRNA operons has important post-transcriptional
      functions for 16S RNA stability and ribosomal subunit stoichiometry. A model is
      proposed, describing the biogenesis and quality control of ribosomes based on
      rRNA leader and Nus-factor interactions. It is compatible with the previously
      observed effects of box A in antitermination.

PMID- 1981804
TI  - Effects of N-methyl-D-aspartate receptor ligands on yeast sporulation.
AB  - Earlier studies have suggested that glutamate may play an important role in the
      transition between the mitotic (vegetative) and meiotic (sporulative) stages of
      the life cycle in the yeast Saccharomyces cerevisiae. Glutamate is also a major
      excitatory neurotransmitter in the vertebrate brain, and its actions are mediated
      by the excitatory amino acid (EAA) family of receptors, the three best
      characterized of which are the N-methyl-D-aspartate (NMDA), quisqualate (Q), and
      kainate (K) receptors. As an initial test of the possibility that glutamate
      action in S. cerevisiae might be mediated by an EAA-like receptor mechanism, the
      effects of ligands that define the functional domains of the vertebrate NMDA
      receptor have been examined. The responses of S. cerevisiae cells to ligands that
      act at four distinct sites on the NMDA receptor provide the first evidence for an
      NMDA-like receptor-mediated system involved in the control of yeast sporulation.

PMID- 1981805
TI  - Release of the vascular permeability factor in minimal change nephrotic syndrome
      is related to CD4+ lymphocytes.

PMID- 1981806
TI  - Dopamine deficiency syndrome in children with a special reaction to treatment
      with levodopa preparations.
AB  - The authors describe the dopamine deficiency syndrome in children with the
      disease beginning during their first year and unusual dystonia symptoms resulting
      in total immobilization and speech loss. All symptoms of the disease can be
      eliminated by low doses of nakom but reappear on withdrawal of the drug. Tyrosine
      hydroxylase studies made on these patients at various stages of the disease
      showed a different pattern of enzyme activity from that observed in children with
      similar pathology failing to improve dramatically under nakom treatment.

PMID- 1981807
TI  - Takayasu's disease.
AB  - A fourteen years old girl developed Takayasu's arteritis (pulseless disease)
      since six months prior to investigation. This unusual form of arteritis is common
      in Japan and Korea but has rarely been reported in individuals born in the United
      States. In Indonesian literature it has never been documented so far. The
      etiology is unclear. The literature currently but forward the hypothesis of an
      autoimmune basis and treatment with steroid. Although a tuberculin sensitization
      pathogenesis has been suggested, a close temporal relationship with the onset of
      a tuberculous process has not previously been documented. The likelihood of
      uncovering tuberculin sensitivity or active tuberculosis in patients with
      Takayasu' arteritis is substantially higher than in the general population in all
      countries analyzed. The natural history of this arteritis is highly variable. The
      adolescent described in this paper has demonstrated no response either to
      antituberculosis therapy, or to heparin and corticosteroid as suggested by
      Ishikawa, 1987. The patient died on the 59th day of hospitalization after getting
      syncopal attacks followed by shock.

PMID- 1981808
TI  - [Risk factors of testicular neoplasms].

PMID- 1981809
TI  - The actions of some beta-receptor agonists and xanthines on isolated muscle
      strips from the human oesophago-gastric junction.
AB  - Isolated preparations from the circular muscle layer of the human oesophago
      gastric junction were mounted in organ baths and isometric tension recorded.
      During an equilibration period, active resting tension developed suggesting that
      the preparations were representing the lower oesophageal sphincter. Active
      tension was abolished by exposing the preparations to Ca(++)-free medium. The two
      xanthines theophylline and enprofylline almost equipotently relaxed the
      preparations in a concentration-dependent manner (10(-7)-10(-3) M). Within
      therapeutic concentrations, theophylline inhibited active resting tension by 30
      60%, while enprofylline lowered tension by less than 20%. Inhibitory actions of
      adenosine were demonstrated, and this suggests that adenosine antagonism is not
      the mechanism of action for xanthines in the oesophagus. Non-selective beta
      receptor stimulation with isoprenaline inhibited active tension by 70% (10(-7)
      M), while beta 2-receptor stimulation with terbutaline inhibited tension by 47%
      (10(-5) M). Dobutamine, believed to preferentially stimulate beta 1-receptors,
      inhibited active tension in a concentration-dependent manner (10(-7)-10(-4) M).
      Metoprolol (10(-6) M), a selective beta 1-receptor antagonist, shifted the
      concentration-response curve for isoprenaline to the right, but left the maximal
      response unchanged. It is concluded that xanthines and beta-receptor agonists
      have inhibitory actions on circular muscle from the human oesophagogastric
      junction. The experimental data suggest the presence of beta 1- as well as beta 2
      receptors, both mediating inhibition of active resting tension.

PMID- 1981810
TI  - Analgesic and behavioural effects of Morinda citrifolia.
AB  - The traditional therapeutic indications for the use of Morinda citrifolia L.
      (Rubiaceae) have been investigated. The lyophilised aqueous extract of roots of
      M. citrifolia was evaluated for analgesic and behavioural effects in mice. The
      extract did not exhibit any toxic effects but did show a significant, dose
      related, central analgesic activity in the writhing and hotplate tests; this
      effect was confirmed by the antagonistic action of naloxone. Furthermore,
      administration of M. citrifolia extract at high dosages decreased all behavioural
      parameters in the two compartment test, the light/dark choice situation test, and
      the staircase test; together with the induced sleeping time, these results are
      suggestive of sedative properties.

PMID- 1981811
TI  - [EEG performance spectral mapping during drug therapy in a patient with
      schizophrenic psychosis].
AB  - In a paranoid-hallucinatoric patient with chronic course and acute exacerbation a
      EEG mapping study during neuroleptic treatment was carried out. The typical
      changes of the alpha power spectra in schizophrenic psychoses as well the
      normalization after neuroleptic treatment could be found in the alpha map. The
      changes were in correlation to the clinical state.

PMID- 1981812
TI  - Workload contribution of a physician assistant in an ambulatory care setting.
AB  - To evaluate the workload contribution of a Physician Assistant (PA) in an
      Ambulatory Care-Walk-in setting the number of patients registered, seen by the
      PA, and by the Supervising Physician (SP) was used. The simple average was drawn
      for comparison purposes. Quality of care assessment done by record review of
      patients seen. The workload contribution of the PA was 10.8%, that of the SP was
      11.6%, with a joint contribution of 22.5%. The non supervising physician average
      was 11.2%. The quality of care assessment showed 100% compliance with the first
      four, and 93% compliance with the last three criteria. A PA makes an efficient
      workload contribution in this setting, not endangering the workload contribution
      of the supervising physician, who is able to maintain a similar workload
      contribution to that of a non supervising physician.

PMID- 1981813
TI  - Defining treatment refractoriness in schizophrenia.
AB  - Addressing the need for research on the nature of refractoriness to antipsychotic
      drug therapy exhibited by a substantial minority of schizophrenic patients,
      Philip R.A. May and Sven Jonas Dencker instigated an international study group to
      discuss this problem, beginning with the International Congress of
      Neuropsychopharmacology in Goteborg, Sweden, in 1980. The study group
      subsequently met in Haar, Federal Republic of Germany, in 1985; in Banff, Canada,
      in 1986; and again in Telfs, Austria, in 1988. The study group set three
      objectives: (1) to clarify the concept of treatment resistance or refractoriness;
      (2) to suggest criteria for defining or rating the degree of treatment
      refractoriness; and (3) to explore the role of psychosocial and drug therapies in
      increasing the responsiveness of the treatment refractory patient. This position
      article represents a distillation of the study group's efforts to define
      treatment refractoriness in schizophrenia.

PMID- 1981814
TI  - Basic principles of recombinant DNA use for prenatal diagnosis.

PMID- 1981815
TI  - The application of oligonucleotide probes to HLA class II typing of the DRB sub
      region.
AB  - A plan for DRB typing at the sequence level is detailed. Only one polymerase
      chain amplification reaction is needed and the application of a limited number of
      short oligonucleotide probes allows an almost complete definition of DRB alleles.
      The scheme was tested on 40 homozygous cell-lines selected to cover a wide range
      of specificities, and 40 RFLP-typed controls. The results are presented and
      discussed. The simplicity and accuracy of this scheme are emphasized.

PMID- 1981816
TI  - Selective PCR-RFLP method to distinguish HLA-DR1 from HLA-DR-"Br" (Dw Bon)
      alleles: applications in clinical histocompatibility testing.

PMID- 1981818
TI  - Dietary lipids and the central nervous system. A symposium. Stockholm, November 2
      3, 1988. Proceedings.

PMID- 1981817
TI  - Effects of intracerebroventricular administration of adrenoceptor-agonists on the
      regulation of renal water and electrolytes handling through endocrine, renal and
      hemodynamic function.
AB  - In order to assess the roles of central adrenoceptors in the release of atrial
      natriuretic peptide (ANP), aldosterone (ALD), vasopressin (AVP) and renin as well
      as in the regulation of renal and cardiovascular functions, either norepinephrine
      (NE; 0.07 microgram/kg/min), guanabenz (GB; alpha 2-agonist; 0.4
      microgram/kg/min), methoxamine (MET; alpha 1-agonist; 0.4 microgram/kg/min), or
      isoproterenol (ISO; beta-agonist; 0.07 microgram/kg/min), dissolved in the
      artificial cerebrospinal fluid (ACSF), was intracerebroventricularly (i.c.v.)
      administered at a rate of 10 microliters/min for 30 min in anesthetized dogs. In
      the control study, the drugs were omitted. NE decreased mean arterial pressure
      (MAP), urinary osmolality (Uosm) and plasma ALD and AVP concentrations, and
      increased urine flow (UF). GB increased UF and urinary K excretion without any
      changes in urinary Na excretion, but decreased plasma ALD and AVP, heart rate,
      and Uosm without changes in MAP. ISO decreased MAP and plasma ALD, and increased
      Na and K output, renal plasma flow and UF with decreased Uosm. MET and ACSF
      failed to affect any of these parameters. Glomerular filtration rate, plasma ANP
      concentration and renin activity did not change in any of the studies. The
      present results suggest that central alpha 2- and beta-adrenoceptors may
      attenuate ALD and/or AVP release without changes in ANP and renin release, and
      decrease blood pressure, thereby causing a diuresis and natriuresis.

PMID- 1981819
TI  - Eicosanoids and the central nervous system.

PMID- 1981820
TI  - Tyrosine hydroxylase- and corticotropin releasing factor-immunoreactivity in the
      olfactory bulb of the opossum (Didelphis virgianina).
AB  - The nerve fiber layer of the opossum olfactory bulb, formed by axons originating
      from bipolar neurons in the olfactory epithelium, and glomeruli are intensely
      immunoreactive for olfactory marker protein. The surrounding extra-glomerular
      neuropil contains numerous periglomerular neurons immunoreactive for either
      tyrosine hydroxylase or corticotropin releasing factor. Dendrites of both types
      of immunoreactive neurons extend into the intraglomerular neuropil. CRF
      immunoreactive neurons are fewer in number than TH-immunoreactive neurons and are
      observed primarily in the periglomerular region. Occasional, scattered TH
      immunoreactive neurons are seen in the deeper layers of the olfactory bulb.

PMID- 1981821
TI  - Effects of long-term administration of gentamicin in the vestibular macula.

PMID- 1981822
TI  - Presence of dipeptidyl aminopeptidase in the developing inner ear of the guinea
      pig as revealed by immunohistochemistry.

PMID- 1981823
TI  - Permethylation and tandem mass spectrometry of oligosaccharides having free
      hexosamine: analysis of the glycoinositol phospholipid anchor glycan from the
      scrapie prion protein.
AB  - Permethylation of the glycan isolated from the glycoinositol phospholipid (GPI)
      anchor of the scrapie prion protein (PrPSc) trimethylates a free hexosamine to
      form a quarternary ammonium salt, substantially increasing the sensitivity for
      analysis by mass spectrometry. This derivatization induces specific fragmentation
      reactions in collision-induced dissociation spectra obtained on a four-sector
      tandem mass spectrometer, identifying the branching pattern of the PrPSc GPI
      glycan.

PMID- 1981824
TI  - Impaired immunity in AIDS. The mechanisms responsible and their potential
      reversal by antiviral therapy.
AB  - The inability of CD4+ T cells of HIV-1-infected patients to mount an effective
      immune response is widely believed to explain the increased susceptibility of
      these patients to opportunistic infections. Although the full explanation for T
      cell dysfunction in HIV-1 infection is not yet understood, at least two
      fundamentally distinct mechanisms are thought to contribute: depletion of CD4+ T
      cells and qualitative CD4+ T-cell dysfunction independent of T-cell depletion.
      Many HIV-1-infected patients manifest reduced T-cell responses to recall antigens
      prior to measurable CD4+ T-cell depletion, and among the proposed explanations
      for this phenomenon are gp120-mediated interference with T-cell activation by way
      of inhibition of CD4-class II major histocompatibility complex (MHC) determinant
      interactions, gp41-mediated inhibition of protein kinase C-dependent T-cell
      activation, formation of gp41 cross-reactive antibodies that react with MHC class
      II determinants, transforming growth factor-beta (TGF-beta)-mediated
      immunosuppression, and decreased functions of antigen-presenting and antigen
      processing cells (macrophages and bone marrow-derived dendritic cells). Despite
      their detection in most HIV-1-infected patients, these qualitative T-cell defects
      do not herald the onset of life-threatening disease. The appearance of severe
      clinical manifestations of AIDS, particularly opportunistic infections, occurs
      primarily in patients whose CD4+ T-cell count is significantly reduced. Depletion
      of CD4+ T cells may be a direct consequence of HIV-1 infection that occurs as a
      result of syncytia formation, autoantibody-mediated cytolysis, gp120-specific
      antibody-dependent cytolysis, and/or gp120-specific T-cell mediated cytolysis.
      The thymus is severely affected in patients with late-stage disease, and although
      there is no proof that the failure of the thymus to regenerate new T cells
      contributes to T-cell depletion in patients with AIDS, the likelihood seems high
      that this is the case. Indeed, if prolonged suppression of HIV-1 replication can
      be achieved with newer anti-HIV drugs or combinations of drugs, reconstitution of
      a normal immune system seems likely, provided that the capacity to regenerate T
      cells has not been irrevocably lost as a consequence of viral infection. In
      summary, available evidence indicates that HIV-1 uses a complex array of
      mechanisms to disrupt T-cell mediated immunity, but because most of these involve
      a direct role for HIV-1 proteins, such mechanisms are likely to be reversible if
      suppression of HIV-1 replication can be achieved.

PMID- 1981825
TI  - Seasonal changes of parafollicular and follicular cells of the dormouse thyroid
      (Myoxus glis): an ultrastructural and immunocytochemical study.
AB  - The follicular epithelium of dormouse thyroid consists of two distinct cellular
      types, follicular and parafollicular cells. Parafollicular cells can be easily
      identified by their high cytoplasmic dye-affinity for phloxine, round to ovoid
      shape, basal arrangement and lack of contact with follicular colloid. The wide
      cytoplasmic matrix is clear and contains many secretory granules of variable
      electron density whose contents histochemically appears to be proteic with a lean
      glucidic component. Furthermore immunocytochemical reactions with antibodies
      against calcitonin and somatostatin showed that both hormones are co-stored in
      the secretory granules of all parafollicular cells. Both follicular and
      parafollicular cells show seasonal morphological variations in their secretory
      activity. Follicular cell activity is high in summer, reaches a peak in late fall
      or prehibernation and progressively slows down throughout hibernation.
      Parafollicular cells exhibit a fair synthetic activity in summer, in fall, and in
      the animals captured during winter hibernating sleep and killed after 12 days
      stay in laboratory. In winter sleep, granules with interrupted membrane and
      cottony contents are prevalent and the ultrastructural aspects suggest an intense
      discharge of secretion. The results are compared with those from other
      hibernating mammalians and discussed in the light of blood calcium values and
      seasonal balances of other metabolisms.

PMID- 1981826
TI  - Impact of methylparathion and malathion on cholinergic and non-cholinergic enzyme
      systems of penaeid prawn, Metapenaeus monoceros.
AB  - The nervous tissue AChE, BUChE and glutaminase activity levels were significantly
      inhibited, whereas glutamine synthetase activity, acetylcholine and glutamine
      contents were increased significantly following the sublethal exposure of prawn,
      Metapenaeus, monoceros to methylparathion and malathion. During OPI exposure
      ammoniagenesis was triggered by increased deamination of purines and oxidative
      deamination of glutamate. This results in the hyperammonemia. As a consequence of
      hyperammonemia, the OPI exposed prawn tissue have adopted the suitable mechanisms
      to detoxity the ammonia by enhancing the synthesis of urea and glutamine. From
      the study, it has been observed that 10 days of reclamation period is not enough
      but the prawn nervous tissue showed efficient mechanisms for the detoxification
      or biodegradation of OPI molecules, which will pave way for the successful
      survival prawns.

PMID- 1981827
TI  - ACNP satellite workshop: Subtypes of receptors for serotonin and their effectors.
      Maui, Hawaii, December 15-17, 1989. Proceedings.

PMID- 1981828
TI  - Quantitative structure-activity relationships of salicylamide neuroleptic agents.
AB  - The in vitro antidopamine activity of substituted N-[(1-alkyl-2
      pyrrolidinyl)methyl]-6-methoxysalicylamides was found to be well correlated with
      the hydrophobic and electronic nature of substituents at the 3-position, and with
      the steric nature of groups replacing the hydrogen atom of the salicyl hydroxy
      group. In contrast, only the hydrophobic and steric characteristics were found to
      be important in the in vivo activity of these neuroleptics. This difference
      suggests that different mechanisms are probably involved in their in vitro and in
      vivo actions, and that the relevant receptors are slightly different in
      structure. The in vitro results suggest that electron donation by the 3
      substituent strengthens the formation of a hydrogen bond between the carbonyl
      group of the amide moiety and a hydrogen of the receptor.

PMID- 1981829
TI  - [Role of beta-2-mimetic agents in the treatment of asthma].
AB  - Recent modifications of pre existing Beta 2 drugs and new substances with a
      prolonged bronchodilator effect may improve asthmatic treatment, in term of
      duration of benefit and compliance to medication. Evaluation of bronchodilation
      is still debated. When single dose of drug is administered, nycthemeral rhythm,
      baseline pulmonary function are to be taken in account. In case of long term
      treatment studies, evaluation of the effects is based upon clinical score,
      sequential pulmonary function tests, morning and evening peak expiratory flow
      rates. Risks way be related to be related to beta 2 drugs or concomitant therapy
      or associated pathology. Indications of dose and route administration are related
      to asthma severity. Question to state if beta 2 drugs may be considered as
      prevention treatment. Studies with compounds exhibiting prolonged bronchodilating
      effect are able to reduce nocturnal asthma, peak flow instability and to improve
      clinical scores and pulmonary function.

PMID- 1981831
TI  - X chromosome linked immunodeficiency.
AB  - Six human immunodeficiency diseases have been associated with the X chromosome by
      family studies. Genetic mapping with restriction fragment length polymorphisms
      (RFLPs) has permitted assignment of these diseases to specific loci on the X
      chromosome. Each of the disease entities maps to a single locus, confirming that
      the diagnostic criteria describe single diseases. X-linked chronic granulomatous
      disease and Wiskott-Aldrich syndrome map to loci on the short arm of the X
      chromosome; X-linked severe combined immunodeficiency, X-linked
      agammaglobulinemia, X-linked immunodeficiency with hyper-IgM, and X-linked
      lymphoproliferative syndrome map to loci on the long arm. Lyon's hypothesis
      predicts that these X-linked immunodeficiencies may be detectable in carriers of
      the diseases as a result of X chromosome inactivation of the normal disease gene.
      Four of the immunodeficiency diseases, X-linked agammaglobulinemia, X-linked
      severe combined immunodeficiency (SCID), Wiskott-Aldrich syndrome, and X-linked
      chronic granulomatous disease, affect cellular development so that carriers have
      a monomorphic population of immunocytes. The specific immunocyte development
      affected in carriers varies according to the disease. Genetic mapping of the
      diseases, with a collection of informative RFLPs, provides a tool that permits
      probability-based prenatal diagnosis. Carrier detection complements the RFLP
      based genetic mapping, serving to confirm X-linkage in carriers.

PMID- 1981830
TI  - Neu (c-erbB-2), a tumor marker in carcinoma of the female breast.
AB  - The c-erbB-2 oncogene encodes a transmembrane phosphoglycoprotein. This molecule
      appears to be a growth factor receptor in the family of tyrosine kinase growth
      factor receptors; however, its ligand has not yet been identified. Amplification
      and/or overexpression of c-erbB-2 in breast adenocarcinomas occurs frequently and
      its occurrence implies a more advanced malignancy. This functional tumor marker
      is readily identified by appropriate DNA and antibody probes. The large external
      domain of the c-erbB-2 gene product is a promising target for immunodiagnostic
      and immunotherapeutic modalities.

PMID- 1981832
TI  - Effect of tiacrilast, a mast cell mediator-release inhibitor, on murine
      experimental contact dermatitis.
AB  - The effect of tiacrilast, a mast cell mediator-release inhibitor, was studied in
      dinitrofluorobenzene-induced allergic and croton oil- or dimethyl sulfoxide
      induced irritant murine contact dermatitis. At 1% concentration, the compound
      significantly reduced the ear swelling in both allergic and irritant dermatitis
      and preserved the mast cell architecture on histopathology. These findings
      suggest that mast cells participate in the elicitation of murine contact
      dermatitis.

PMID- 1981833
TI  - Vaccine and AIDS. San Marino Conference. Republic of San Marino, October 7-11,
      1990. Abstracts.

PMID- 1981835
TI  - [The role of protirelin tartrate (TRH-T) in the rehabilitation of the post-stroke
      patient. XC National Congress of the Italian Society of Internal Medicine. Rome,
      16-20 October 1990].

PMID- 1981834
TI  - Human immunodeficiency virus (HIV) circulating immune complexes in infected
      children.
AB  - Circulating immune complexes (CIC) were studied for the presence of human
      immunodeficiency virus (HIV) antigens (HIV-Ag) in 55 children infected by the
      human immunodeficiency virus type 1 (HIV-1). CIC were elevated in 85% of
      patients. In 33 of 55 patients CIC included at least one HIV-Ag (HIV-Ag-CIC).
      Sixty percent of patients had p17 antigen, 50% had p24 antigen, and 16% had gp120
      associated with CIC. Levels of HIV-Ag-CIC did not correlate with free serum HIV
      antigens. Patients with high HIV-Ag-CIC had a more severe clinical course and 90%
      of those with markedly elevated HIV-Ag-CIC (greater than 3+) have died within 6
      to 24 months. HIV-Ag-CIC were also present in some patients including neonates
      and young infants in whom free HIV-Ag was undetectable. Monitoring of HIV-Ag in
      isolated CIC may be of value for early detection of HIV infection and for
      monitoring of disease outcome.

PMID- 1981837
TI  - [Diagram for management of dental trauma].

PMID- 1981836
TI  - Cyclic GMP alterations in fetal rat cerebrum after global intrauterine ischemia:
      role of guanylate cyclase phosphorylation.
AB  - Changes in the levels of cyclic AMP (cAMP) and cyclic GMP (cGMP) have been
      measured in brains of 20-day-old rat fetuses exposed to global intrauterine
      ischemia. Ischemia of different duration (0.5-30 minutes) did not alter the level
      of cAMP. In contrast, cGMP levels increased as a result of ischemia. This
      increase was seen even after a short period of ischemia (less than 5 minutes) and
      was maximal after 5 minutes, where a threefold increase could be observed. This
      stimulation was transient: after 30 min of ischemia, cGMP returned to the control
      level. Accumulation of cGMP can be related to the activation of guanylate
      cyclase, the activity of which is doubled after 15 minutes of ischemia.
      Immunoprecipitation of guanylate cyclase after in vivo labeling of the fetal
      brain with 32Pi revealed a threefold increase in the phosphorylation of the
      enzyme after 15 minutes of ischemia. The possible role of these modifications in
      cGMP metabolism during the course of ischemia is discussed.

PMID- 1981838
TI  - Presumptive catecholaminergic ganglion cells in the pigeon retina.
AB  - An antiserum directed against tyrosine hydroxylase (TH), the rate-limiting enzyme
      in the synthesis of dopamine, was used to study the pigeon retina. Labeled cells
      were observed in both the inner nuclear layer (INL) and ganglion cell layer
      (GCL). Two populations of TH-immunoreactive neurons were observed in the INL.
      Some of these cells were 7-10 microns in diameter and gave rise to processes that
      arborized in three layers of the inner plexiform layer (IPL). These cells
      appeared similar to the dopaminergic amacrine cells described previously (Marc,
      1988). Other labeled cells in the INL were 12-20 microns in diameter and were
      recognizable as a previously described subpopulation of TH-immunoreactive
      displaced ganglion cells (Britto et al., 1988). A population of labeled cells was
      observed in the GCL. Counts of these cells in two retinae revealed 5000 and 7000
      cells, respectively. They ranged in size from 8-15 microns in diameter in the
      central retina and from 8-20 microns in diameter in the peripheral retina. The
      density of labeled cells was highest in the central retina and red field and
      lowest in the retinal periphery. The difference in cell size and cell density as
      a function of eccentricity is characteristic of the total population of ganglion
      cells in the avian retina (Ehrlich, 1981; Hayes, 1982). Some of the TH-positive
      cells in the GCL could be classified as ganglion cells for two reasons: (1) The
      axons of many of the TH-positive cells in the GCL were TH-immunoreactive as well
      and could be followed to the optic nerve head. (2) The injection of rhodamine
      labeled microspheres into the nucleus geniculatus lateralis, pars ventralis
      (GLv), resulted in the retrograde labeling of many of the TH-positive cells in
      the contralateral retina.

PMID- 1981839
TI  - A submicroscopic homozygous deletion at the D3S3 locus in a cell line isolated
      from a small cell lung carcinoma.
AB  - We have used 14 DNA probes, which detect 19 different restriction enzyme length
      polymorphisms, to search for heterozygosity on chromosome 3 in five cell lines
      isolated from patients with small cell lung carcinoma. The cell lines on
      karyotype analysis did not show the deletion in chromosome 3 characteristic of
      this disease. Our objective was to determine if allelic loss had occurred by some
      chromosomal mechanism other than deletion. Two of the cell lines are consistent
      with allelic loss having occurred by whole chromosome loss and reduplication. The
      third may have lost only the short arm due to i(3q) formation. The fourth cell
      line has an i(3q) chromosome, together with a translocation product involving the
      distal portion of the short arm of chromosome 3. Lack of evidence of
      heterozygosity for this distal portion of 3p suggests that a copy of the 3p
      homologue is involved in the translocation and therefore does not explain allelic
      loss of of the other homologue. The fifth, while also likely to have lost one
      chromosome homologue, has a submicroscopic deletion on all chromosome 3s, only
      detectable by RFLP analysis. Such homozygous deletions have recently proved
      useful in the isolation of tumour suppressor genes.

PMID- 1981840
TI  - Biologically Engineered Polymers 1989. A conference. 31 July-2 August 1989,
      Cambridge, United Kingdom. Proceedings.

PMID- 1981841
TI  - Overcoming inhibitions. Translational Control sponsored by the Cold Spring Harbor
      Laboratory, Cold Spring Harbor, NY, USA, September 13-17, 1989.

PMID- 1981842
TI  - Yeast cell biology: the wave of the present. Yeast Cell Biology sponsored by the
      Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA, August 15-20, 1989.

PMID- 1981843
TI  - A cyclin built for two. New Approaches to Understanding Cell Cycle Regulation
      sponsored by the Molecular Biology and Molecular Cytology Study Sections,
      Division of Research Grants, National Institutes of Health Bethesda, MD, USA,
      October 11, 1989.

PMID- 1981844
TI  - Human immunodeficiency virus type-2 gene expression: two enhancers and their
      activation by T-cell activators.
AB  - The human immunodeficiency viruses (HIVs) may include a spectrum of retroviruses
      with varying potential to infect their host, undergo long periods of latent
      infection, and induce pathology. Since expression of the viruses is in large part
      regulated by the sequence elements in their long terminal repeats (LTRs), this
      study was directed to an analysis of the regulatory elements in the HIV-2 LTR.
      The HIV-2 LTR was found to contain two enhancers. One of these enhancers is, in
      part, identical to the HIV-1 enhancer. This enhancer in HIV-1 is the T-cell
      activation response element; in HIV-2, however, it is the second enhancer that is
      mainly responsible for activation in response to T-cell activators. The second
      enhancer interacts with two nuclear binding proteins (85 kD and 27 kD mobility)
      that appear to be required for optimal enhancer function and activation.
      Observations such as these encourage the speculation that there may be subtle
      differences in the regulation of HIV-1 and HIV-2 expression that may be relevant
      to the possible longer latency and reduced pathogenicity of HIV-2.

PMID- 1981845
TI  - The peach, the fly, and the patterns of life. Cell-cell Interactions in Early
      Development, the Forty-Ninth Annual Symposium of the Society for Developmental
      Biology, Washington, DC, USA, June 27-30, 1990.

PMID- 1981846
TI  - September 14, 1990: the beginning.

PMID- 1981847
TI  - Interaction of ATP with acetyl-CoA carboxylase from rat liver. The role of the
      polyphosphate chain. Affinity labelling with alkylating amides of ATP and ADP.
AB  - The interaction of a number of ATP analogs with a modified triphosphate moiety as
      well as 2-chloro-ethyl-amino derivatives of nucleotides, 4(N-2-chloroethyl-N
      methylamino)-benzyl-gamma-amide of ATP and the corresponding ADP beta-amide with
      acetyl-CoA carboxylase (EC 6.4.1.2.) from rat liver has been studied.
      Halophosphonate derivatives of ATP have been synthesized from bromomethylene
      diphosphonic acid and found to be reversible inhibitors of the enzyme. ATP and
      ADP alkylating amides have proved to form a reversible complex with the ATP
      binding site and to modify a group in the acetyl-CoA-binding site. The
      bicarbonate ion accelerates the process of inactivation. The estimate of the
      distance between the ATP-binding site and the acetyl-CoA-binding site ranges
      within 0.8-1.2 nm.

PMID- 1981848
TI  - [Subcellular distribution of adenosine system enzymes in the hypothalamus and
      hippocampus of the rat brain].
AB  - The subcellular distribution of 5'-nucleotidase and adenosine deaminase in rat
      brain hypothalamus and hippocampus was studied. In the hippocampus the 5'
      nucleotidase activity was shown to be much higher than in the hypothalamus, while
      the adenosine deaminase activity, contrariwise, is nearly two times as high as
      that in the hypothalamus. During the analysis of subcellular distribution 5'
      nucleotidase and adenosine deaminase were detected in all fractions under study,
      i. e., in nuclear, soluble, myelin fractions as well as in synaptic membranes,
      synaptosomes and "pure" mitochondria. The highest 5'-nucleotidase activity was
      found in the myelinic and synaptic fractions both in the hypothalamus and in the
      hippocampus. The highest adenosine deaminase activity was detected in the soluble
      fraction of the above structures. The enzyme activity in synaptic membranes and
      synaptosomes was nearly two times as low.

PMID- 1981849
TI  - [Role of aminopeptidases in enkephalin catabolism: comparative study of the
      regional distribution of aminopeptidases and enkephalinase A in the rat brain].
AB  - In order to elucidate the role of aminopeptidases in enkephalin catabolism in rat
      brain, the local distribution of two types of cerebral cellular membrane
      aminopeptidases (puromycin-sensitive and puromycin-insensitive ones) and of the
      enkephalin system marker, enkephalinase A, was studied. It was found that the
      distribution patterns of the former enzymes differ essentially from that of
      enkephalinase A. Study of coupling between the enzymatic activities in different
      regions of rat brain revealed a strong correlation between the activities of
      puromycin-insensitive aminopeptidase and enkephalinase A in midbrain (including
      hypothalamus). It was supposed that in midbrain the role of aminopeptidase M in
      intrasynaptic inactivation of enkephalins is much more conspicuous than in other
      regions of rat brain. The puromycin-sensitive aminopeptidase activity does not
      seem to play a role in enkephalin catabolism.

PMID- 1981850
TI  - [An endogenous regulator of the guanylate cyclase activity of human platelets].
AB  - Chromatography of soluble human platelet guanylate cyclase (105,000 g
      supernatant) on DEAE-cellulose in a linear gradient of NaCl (0-0.5 M) in 50 mM
      Tris-HCl buffer pH 7.6 gave two protein peaks, I and II, of which only peak II
      possessed the guanylate cyclase activity (0.18-0.22 M NaCl). The protein fraction
      I was found to possess an inhibiting activity; its addition to the partially
      purified enzyme decreased the guanylate cyclase activity by 60-70% in the
      presence of Mg2+ with no effect on the enzyme activity in the presence of Mn2+.
      The isolated enzyme lost (by approximately 80%) its ability to be activated by
      sodium nitroprusside; the latter was reconstituted after addition of the
      inhibiting fraction. The data obtained testify to the heme origin of the
      endogenous inhibitor of human platelet guanylate cyclase.

PMID- 1981852
TI  - Zolantidine-induced attenuation of morphine antinociception in rhesus monkeys.
AB  - The effect of zolantidine dimaleate (ZOL), the first brain-penetrating histamine
      H2 receptor antagonist, was determined on morphine (MOR) antinociception (ANC) in
      rhesus monkeys. ZOL (0.75 mg/kg, s.c., given every 30 min), completely attenuated
      the ANC resulting from the lowest dose of MOR tested (1.0 mg/kg), with no effect
      on the responses to higher doses (3-10 mg/kg). ZOL had no effect on baseline
      nociceptive responses in the absence of MOR. Taken with previous studies on the
      pharmacological specificity of ZOL, the ANC properties of histamine, and more
      extensive studies in rodents, the present results suggest that opiates like MOR
      relieve pain in primates by mechanisms that include activation of brain H2
      receptors.

PMID- 1981851
TI  - [Effect of N-(6-aminohexyl)-5-chloronaphthalene-1-sulfamide (W-7) and its analogs
      on the activity of soluble guanylate cyclase and on human platelet aggregation].
AB  - The effect of N-(omega-aminoalkyl) derivatives of naphthalene-1-sulfamide on the
      activity of soluble guanylate cyclase and on human platelet aggregation at the
      first (reversible) step of the guanylate cyclase reaction was studied. Low
      (approximately 10(-7)-10(-6) M) concentrations of the above compounds were shown
      to stimulate the guanylate cyclase activity; some derivatives caused simultaneous
      inhibition of platelet aggregation induced by ADP. Some fragments of the chemical
      structure of the molecules responsible for the enzyme activity regulation in the
      tested systems were identified. The naphthalene-1-sulfamide derivatives carrying
      6-aminohexyl or 8-amino-octyl groups of the sulfamide substituent as well as
      chlorine atom at positions 4 or 5 of the naphthalene ring appeared to be the most
      potent activators of platelet guanylate cyclase and inhibitors of platelet
      aggregation at the reversible step of the enzymatic reaction.

PMID- 1981853
TI  - Nigrostriatal dopamine mediates the stimulatory effects of corticotropin
      releasing factor on methionine-enkephalin and dynorphin release from the rat
      neostriatum.
AB  - This study examined the effects of corticotropin-releasing factor (CRF) on the in
      vitro release of methionine-enkephalin (Met-enkephalin) and dynorphin in
      neostriatal slices taken from rats with unilateral 6-hydroxydopamine (6-OHDA)
      induced lesions of the nigrostriatal DA pathway. In neostriatal slices from
      control saline-infused animals and in those from the contralateral hemisphere of
      6-OHDA-lesioned animals, CRF (10(-10) M) administered as a 90-min pulse exerted
      potent stimulatory effects on both Met-enkephalin and dynorphin release. In the
      neostriatal slices of 6-OHDA-lesioned striata, both the basal release and tissue
      content of Met-enkephalin were significantly (P less than 0.01) higher (2-fold)
      than those of control animals and the contralateral hemisphere of 6-OHDA-lesioned
      animals; however, neither the basal release nor the tissue content of dynorphin
      in 6-OHDA-lesioned striata was significantly different from control striata. In
      response to CRF (10(-10) M) the release of both Met-enkephalin and dynorphin were
      significantly diminished in slices of 6-OHDA-lesioned striata. These data support
      previous studies suggesting that nigrostriatal DA itself may exert a tonic
      inhibitory action on the activity of striatal Met-enkephalin neurones; however,
      DA may not have the same influence on striatal dynorphin neurons. However, the
      results of this study demonstrate that the action of CRF on Met-enkephalin as
      well as dynorphin release from the rat neostriatum is DA dependent. The data
      suggest that CRF receptors in the rat neostriatum may be localized on
      nigrostriatal/nigropallidal DA terminals/collaterals.

PMID- 1981854
TI  - Esmolol: effects on isoprenaline- and exercise-induced cardiovascular stimulation
      in conscious dogs.
AB  - Esmolol, a recently developed ultra-short acting beta-adrenoceptor blocking
      agent, was evaluated in 12 conscious chronically instrumented dogs with intact
      autonomic reflexes. The significance of its beta 1-adrenoceptor selectivity was
      examined at various cardiovascular activation levels established by either
      incremental isoprenaline infusion or graded treadmill exercise. The observed
      parameters were heart rate, systolic and diastolic arterial blood pressure, left
      ventricular dp/dtmax, and left ventricular end-diastolic pressure. Intravenous
      infusion of esmolol (25 and 250 micrograms.kg-1.min-1) led to a dose-dependent
      reduction of the isoprenaline-induced increase in positive dp/dtmax. The
      concomitant increase in heart rate was suppressed to a lesser extent.
      Characteristically of a beta 1-selective agent, esmolol had only a slight effect
      on the isoprenaline-induced reduction in diastolic blood pressure. The impact of
      esmolol on exercise-induced hemodynamic activation was much smaller. Exercise
      induced increase in positive dp/dtmax was more sensitive to beta-adrenoceptor
      blockade than the concomitant increase in heart rate. Diastolic blood pressure
      was not influenced significantly. beta-Adrenoceptor blockade was virtually
      reversed within 20 min of discontinuation of esmolol infusion.

PMID- 1981855
TI  - Alpha 1-adrenergic partial agonists utilize cytosolic Ca2+ more effectively for
      contraction in aortic smooth muscle.
AB  - Fura 2 loaded thoracic aorta strips from rabbits were used. Norepinephrine,
      phenylephrine, clonidine, and tizanidine induced an increase in cytosolic Ca2+
      concentration [( Ca2+]i) and muscle tension in a concentration-dependent manner.
      A positive correlation between [Ca2+]i and tension development owing to the
      agonists was noted. The slope of regression lines between [Ca2+]i and tension
      development for clonidine and tizanidine, alpha 1-adrenergic partial agonists,
      were significantly steeper than those for norepinephrine and phenylphrine, alpha
      1-adrenergic full agonists. The intrinsic activities of the partial agonists
      obtained from tension development were greater than those from changes in
      [Ca2+]i. These results suggest that the partial agonists cause a greater muscle
      tension than the full agonists at the same level of [Ca2+]i.

PMID- 1981856
TI  - Characterization of myometrial desensitization to beta-adrenergic agonists.
AB  - Continuous exposure of ovine myometrial strips exposed to isoproterenol (10
      microM) resulted in only transient inhibition with contractions returning within
      60 min. Rechallenging these strips with isoproterenol failed to induce
      inhibition, confirming the occurrence of desensitization. In contrast, exposure
      of myometrial tissue to isoproterenol for only 5 min did not result in
      desensitization. Myometrial strips exposed to isoproterenol demonstrated a
      significant increase in cAMP content associated with inhibition of contractile
      activity and a subsequent fall in cAMP content upon desensitization. Elevation of
      endogenous cAMP levels by either inhibition of cAMP-dependent phosphodiesterase
      activity (0.5 mM isobutylmethylxanthine, in ovine strips) or direct activation of
      adenylyl cyclase (10 microM forskolin, in rat strips) induced a rapid and
      significant inhibition of myometrial contractile activity in desensitized tissue.
      Scatchard analysis of the binding of the beta-adrenoceptor antagonist,
      [125I]iodocyanopindolol, revealed a significant reduction in the concentration of
      beta-adrenergic receptors (but no change in binding affinity) in desensitized
      myometrial tissue. Incubation of desensitized tissue with fresh buffer for 3 h
      induced only a partial recovery in responsiveness to isoproterenol. These data
      suggest that prolonged, but not acute, exposure of the myometrium to beta
      adrenergic agonists induces a state of desensitization that is associated with a
      down-regulation of beta-adrenoceptors but maintenance of postreceptor function.

PMID- 1981857
TI  - [The role of intra- and extracellular Ca++ in coronary vessel contraction induced
      in vitro by noradrenaline following a beta-adrenergic block].
AB  - Previous studies reported that norepinephrine (NE) induces contraction of the
      calf isolated coronary arteries after beta-adrenergic blockade with propranolol
      (PR), and that the effect disappeared after phentolamine. An higher Ca++
      concentration increased the response of preparation to NE, whereas the reduction
      of the concentration reduced the response. In isolated coronary arteries the
      baseline tone and contractile response to NE after PR were studied as influenced
      by DA and nicardipine (NI). NI always induced vessel relaxation and DA induced a
      contraction followed by relaxation. The NE contraction was not abolished in
      calcium-free medium but in presence of DA and was reduced by NI in the medium
      containing Ca++. We conclude that NE induces contractions by facilitating the
      influx of the extracellular Ca++ and by promoting the liberation of intracellular
      bound Ca++.

PMID- 1981858
TI  - [The midterm clinical results of myocardial revascularization with the internal
      mammary artery].
AB  - After a 3-year (1985-1988) experience of myocardial revascularization using
      internal mammary artery (AMI) grafts and after having excluded (1986) an higher
      operative mortality and morbidity, clinical medium-term results have been
      analysed. The first 144 patients discharged alive after AMI bypass surgery in
      1985 were clinically evaluated, with a mean interval of 21 months from surgery
      (range: 5-29 months). Exercise electrocardiographic test was performed by 100
      patients, and angiography repeated in 15. Actuarial survival function was
      estimated by Cutler-Ederer method: 2-year actuarial survival was 99.3 +/- 0.7%
      (94 +/- 1.8%, when operative deaths were included). Non fatal myocardial
      infarction occurred in 3 patients and, at follow-up, 26 were symptomatic for
      angina: 2 patients underwent re-operation and 2 angioplasty. Two years after AMI
      bypass surgery, actuarial estimate of ischemic event-free patients was 70.9 +/-
      4.5% (67.7 +/- 4.5%, when operative deaths were included): 73 out of 100 exercise
      tests were negative for both angina and ischemia, although only 43 patients,
      reached maximal work load; 9 were positive for both angina and ischemia and 18
      for ischemia only. All patients who underwent angiographic evaluation (15
      patients, 11 of whom because of angina relapse) had AMI grafts open, while in
      only 4 patients all the implanted grafts were open.

PMID- 1981860
TI  - [Pharmacology of a new antihypertensive agent, metazosin (Kenosin)].
AB  - Metazosin (KENOSIN) displaces 3H-prazosin from its bond to alpha-1 receptors of
      the cerebral cortex, antagonizes the effects of phenylephrin on spinal rats and
      on perfused peripheral vascular regions, which demonstrates that it is a blocker
      of alpha-1 adrenergic receptors. It does not affect the central alpha-2
      adrenergic receptors. No peripheral antiserotonin effect was found. Metazosin
      decreases the blood pressure in normotensive and hypertensive animals. On
      intravenous administration, the decrease commences very rapidly after the onset
      of administration. In dogs, systolic and diastolic blood pressure, cardiac
      output, peripheral resistance and pressure in the pulmonary artery are decreased.
      In animals with experimentally increased pressure in the lesser circulation it
      produces a decrease in pressure. On the basis of hypotensively active doses in
      experimental animals, the administration of 5 mg was proposed as the clinica
      pose. Results of the 1st stage of clinical trials have demonstrated that this
      dose is effective in persons with the systolic pressure higher than 120 mm Hg. At
      present the effect of metazosin is tested on hypertonic patients.

PMID- 1981859
TI  - Somatostatin-binding sites on rat telencephalic astrocytes. Light- and electron
      microscopic studies in vitro and in vivo.
AB  - Using a somatostatin-gold conjugate as ligand, high-affinity binding sites for
      this neuropeptide were demonstrated at three levels: (i) cultured astrocytes from
      rat cortex, (ii) hippocampal slice cultures, and (iii) frozen tissue sections of
      rat telencephalon. The conjugate proved as active as the native peptide in
      competing for the binding sites. Light-microscopic visualization of bound ligand
      was achieved by silver intensification of the colloidal gold. This method is
      faster and yields superior resolution compared with autoradiography. Cultured
      astrocytes from cortex and hippocampus could be labeled by the ligand. At the
      light- and electron-microscopic level, astrocytes could be double-labeled by the
      somatostatin-gold conjugate and immunostaining for glial fibrillary acidic
      protein (GFAP). In hippocampal slice cultures, the conjugate did not penetrate
      into the neuropil because of a covering glial layer. However, a portion of this
      completely GFAP-positive covering glia reacted with the somatostatin ligand. In
      frozen brain sections, apart from delicate punctate structures, two types of
      labeled glia cells were seen: single stellate astrocytes and perivascular glia
      cells.

PMID- 1981862
TI  - [Spontaneous ascent of testes originally located in the scrotum].
AB  - The authors draws attention to possible postnatal changes the position of the
      testicle in the sensent of ascent. According to data in the literature and the
      author's own experience this ascent usually occurs as late as during school age.
      Causes of the altered position of the testicle are discussed. The condition is
      nowadays accepted but it is rare. From the practical aspects it is, however,
      necessary to examine the genitals of boys repeatedly and not only by a single
      examination. In case of a permanently inguinal position of the testicle the boy
      should be referred to a surgical department to prevent secondary damage of the
      testis by its incorrect position.

PMID- 1981861
TI  - Plastid inheritance in Pisum sativum L.
AB  - Cultivar variability for levels of plastid DNA (cpDNA) in the germ cell line of
      germinated pea pollen has suggested the possibility of biparental plastid
      transmission. In order to examine this possibility further, RFLP markers were
      used to follow the transmission of cpDNA from parents to their F1 offspring.
      Results from these inheritance studies clearly indicate the presence of only
      maternal plastid markers in the F1 progeny of each cross examined, irrespective
      of the pollen cpDNA levels of the paternal parent. The same result is obtained
      for F1 progeny produced from crosses using pollen characterized by comparatively
      high cpDNA content, even when offspring are sampled at early developmental
      stages. Thus, there appears to be little correspondence between pollen
      cytological data indicating potential paternal plastid transmission and data from
      molecular marker studies confirming that P. sativum generally follows a
      uniparental-maternal mode of plastid inheritance. Insufficient F1 progeny were
      examined to exclude instances of trace biparentalism.

PMID- 1981863
TI  - [Abnormal placement of the testes].
AB  - The authors defined a uniform classification of abnormal positions of the testes.
      They recommend also a uniform therapeutic procedure: after the first year of life
      treatment with human chorionic gonadotropin in one or two curves, if orchiopexy
      fails.

PMID- 1981864
TI  - [Experimental cryptorchism].
AB  - The authors evaluate the effect of hormonal treatment with chorionic gonadotropin
      on histological structures of the testes in experimental work and in artificially
      induced cryptorchism in the rabbit; they evaluate histological findings in
      cryptorchid and normally descended testes.

PMID- 1981865
TI  - [Role of central endogenous dynorphin in control of ACTH and prolactin release
      during resting and stress].
AB  - To determine the role of central endogenous dynorphin (Dyn) in resting and stress
      induced release of ACTH and prolactin (PRL), Dyn (1-17) antiserum (AS) or normal
      rabbit serum (NRS) were microinjected into the 3rd ventricle of freely-moving
      male rats. Plasma ACTH and PRL levels were measured by radioimmunoassay (RIA)
      using RIA kits supplied by NIADDK. Our results clearly indicate that Dyn (1-17)
      AS and NRS had no effect on resting secretion of ACTH and PRL, and restraint
      stress-induced release of ACTH and PRL were simultaneously lowered significantly
      in the Dyn (1-17) AS-treated group as compared with the NRS-treated group. The
      results suggest that central endogenous dynorphin plays an important role in
      stimulating the concomitant release of ACTH and PRL under certain stresses.

PMID- 1981866
TI  - [Immunofluorescent studies on cytoplasmic microtubule complex (CMTC) of Vero
      cells treated with 5,6-diphenylpyridazin-3-one derivatives].
AB  - Effects of six derivatives of 5,6-diphenyl-pyridazin-3-one (DPP) on CMTC of Vero
      cells were studied by means of the tubulin indirect immunofluorescence technique.
      Results showed that the effects were different with different derivatives and
      dose-dependent. Although PD033 had been know to be potent in inhibiting
      microtubule assembly in vitro, it showed little effect on disturbing CMTC in
      vivo. Besides having the effects mentioned above, PD032 also induced the
      formation of free microtubules similar to those induced by taxol.

PMID- 1981867
TI  - CAPD: host defence, nutrition and ultrafiltration. Report of an international
      conference. London, November 1989.

PMID- 1981868
TI  - Dendritic keratopathy associated with beta-blocker eyedrops.
AB  - Four patients with chronic open-angle glaucoma developed a dendriform corneal
      epithelial lesion. Two were associated with the use of topical betaxolol for 2
      months and 6 weeks, and two were related to topical levobunolol. Resolution
      occurred within 2 weeks of discontinuation of the beta-blocker eyedrop. The
      distinctive pattern of dendritic epithelial keratopathy associated with these
      topical medications may be due to epithelial toxicity with subsequent
      regeneration.

PMID- 1981870
TI  - 4th International Symposium on Hypertonic Resuscitation (Salt IV). Garmisch
      Partenkirchen, FRG, June 17-19, 1990. Abstracts.

PMID- 1981869
TI  - Remoxipride. A review of its pharmacodynamic and pharmacokinetic properties, and
      therapeutic potential in schizophrenia.
AB  - Remoxipride is a substituted benzamide of the same class as sulpiride, and has a
      pharmacodynamic profile consistent with central antidopaminergic activity. It is
      a weak, but relatively selective, central dopamine D2-receptor antagonist and
      appears to have preferential affinity for extrastriatal dopamine D2-receptors. It
      also has marked affinity for central sigma receptors. Clinical data from
      noncomparative and comparative studies show that remoxipride has antipsychotic
      acticvity in patients with chronic schizophrenia, and acute exacerbation of
      chronic schizophrenia, with activity on both positive and negative symptoms. Its
      overall efficacy in these studies was similar to that of haloperidol.
      Importantly, however, remoxipride produced a substantially lower incidence of
      extrapyramidal effects than haloperidol. Further long term comparative studies
      are required to ascertain the relative suitability of remoxipride for preventing
      relapse in psychotic patients, and to determine whether tardive dyskinesia occurs
      in remoxipride recipients--the latter has not been reported with remoxipride to
      date. Thus, while further experience (particularly of a long term comparative
      nature) is needed, at present remoxipride appears to offer an important
      tolerability advantage over haloperidol.

PMID- 1981871
TI  - Epileptiform activity induced by 4-aminopyridine in rat amygdala neurons: the
      involvement of N-methyl-D-aspartate receptors.
AB  - The involvement of the N-methyl-D-aspartate (NMDA) receptor in the epileptiform
      activity induced by 4-aminopyridine (4-AP) was studied in rat amygdala slices
      using intracellular recording techniques. Stimulation of the ventral endopyriform
      nucleus evoked an excitatory postsynaptic potential (EPSP). After exposure to 4
      AP (200 microM) the amygdala slices usually exhibited spontaneous and evoked
      epileptiform activity. The epileptiform events had an average duration of 522 +/-
      78 ms with a frequency of 0.5-8.5 bursts/min. Superfusion of 6-cyano-7
      nitroquinoxaline-2,3-dione (CNQX), a selective non-NMDA receptor antagonist,
      practically abolished the epileptiform bursting. However, there remained a
      residual depolarizing component in 13 out of 18 neurons. This CNQX-resistant
      component was markedly enhanced both in amplitude and duration when extracellular
      Mg2+ was removed and could be reversibly blocked by the specific NMDA receptor
      antagonist, DL-2-amino-5-phosphonovaleate (DL-APV). Compared with the CNQX
      sensitive component, the APV-sensitive component had a much smaller amplitude
      shorter duration. These data suggest that the NMDA receptor is likely to play
      only a minor role, and activation of the NMDA receptor may contribute to but is
      not required, for the generation of these bursts.

PMID- 1981872
TI  - Pharmacological evaluation of the beta-adrenoceptor agonist properties of N
      benzyl substituted trimetoquinol analogues.
AB  - The beta 1- and beta 2-adrenoceptor agonist properties of trimetoquinol (TMQ, I)
      and N-benzyl ring substituted TMQ analogues (II, 4'-methylbenzylTMQ; III, 4'
      chloro-benzylTMQ; IV, 4'-methoxybenzylTMQ; V, 4'-nitrobenzylTMQ; VI, 3',4'
      dichlorobenzylTMQ; and VII, 4'-aminobenzylTMQ) were studied in guinea pig atria
      and trachea. All compounds gave concentration-dependent responses in atria and
      trachea, and the rank order of beta-adrenoceptor agonist potency was I greater
      than VII greater than II greater than V greater than IV greater than VI greater
      than III and I greater than VII greater than IV = VI greater than V greater than
      III greater than II, respectively. Whereas the N-benzyl substitution reduced
      potency for beta-agonist activity, the beta 2/beta 1-selectivity ratio was
      enhanced by addition of groups to the N-benzyl ring, and the rank order of beta 2
      selectivity was VI (10-fold) greater than III (8-fold) = IV (8-fold) greater than
      VII (3-fold) greater than V = I greater than II. The results show that varying
      the nature of substituents on the N-benzyl ring of TMQ produces compounds which
      retain greater beta 2-selectivity.

PMID- 1981873
TI  - Receptor mechanisms for 5-hydroxytryptamine (5-HT) in isolated ovine umbilical
      vein.
AB  - 5-Hydroxytryptamine (5-HT) and 2,5-dimethoxy-4-methyl-amphetamine (DOM) produced
      a concentration-dependent contraction in isolated umbilical veins obtained from
      fetal lambs within 2 weeks of term. Contractions to 5-HT were antagonized by
      ketanserin, mianserin and methiothepin with the dissociation constants (KB) being
      2.17 +/- 0.36, 1.37 +/- 0.55 and 1.98 +/- 0.48 nM, respectively. The order of
      potency of serotonergic agonists in this tissue was: DOM greater than 5-HT
      greater than alpha-methyl-5-HT greater than 1(3-chlorophenyl) piperazine (mCPP)
      greater than m-trifluoromethyl-phenylpiperazine (TFMPP) greater than 8-hydroxy
      dipropylaminotetralin (8-OH-DPAT) = 2-methyl-5-HT. alpha-Methyl-5-HT was a full
      agonist compared to 5-HT. DOM possessed greater affinity but less efficacy than
      that of 5-HT. The affinities and efficacies of the other agonists studied were
      lower than those of 5-HT. Variation in the sensitivity and potency of agonists is
      primarily due to variations in their affinity for 5-HT receptors. Assessment of
      receptor occupancy vs. functional response demonstrated very little, if any,
      receptor reserve for 5-HT receptors in this tissue. Contractile responses to DOM,
      8-OH-DPAT, mCPP and 2-methyl-5-HT were effectively blocked by ketanserin. The
      dissociation constants (KB) of ketanserin against these agonists were as follows:
      DOM, 2.78 +/- 0.85 nM; 8-OH-DPAT, 3.47 +/- 1.12 nM; mCPP, 1.45 +/- 0.51 nM; 2
      methyl-5-HT, 1.99 +/- 0.74 nM. The dissociation constant of MDL 72222 (3-tropanyl
      3,5-dichlorobenzoate) vs. 5-HT was 13833 nM. No antagonism by prazosin (10(-7) M)
      or yohimbine (10(-7) M) of the responses to 5-HT was observed. These results
      indicate that 5-HT2 receptors are present in the ovine umbilical vein. 5-HT3
      receptors were not present in this tissue. Activation of alpha-adrenoceptors was
      not involved in the contractions to 5-HT.

PMID- 1981874
TI  - The mammary gland and integumentary system of laboratory animals. International
      Symposium and Histopathology Seminar, Chuominkan, Nara city, Japan, 5th-8th
      April, 1989. Abstracts.

PMID- 1981875
TI  - The mouse erythrocyte binding receptor is expressed on human keratinocytes.
AB  - Immunocytes and different types of epidermal cells share cell surface antigen
      characteristics e.g. keratinocytes react specifically with the Leu 11 (CD16)
      monoclonal antibody and they express MHC class II and OKM5 (CD36) antigens after
      gamma-interferon stimulation. The present study provides evidence that a
      subpopulation of human keratinocytes most probably at a certain stage of
      differentiation, possesses the mouse erythrocyte binding receptor the marker of a
      human B lymphocyte subset. This finding is a further evidence for the
      relationship between the epidermis and the immune system.

PMID- 1981877
TI  - [Potassium dependency of the effect of beta-adrenergic substances on spontaneous
      activity of human myometrium strips in vitro].

PMID- 1981876
TI  - [Structure and function of the receptors of human thrombocytes].

PMID- 1981878
TI  - Down-regulation of steroidogenic cytochrome P450XVII in cryptorchid rat testes.
AB  - The objective of the present study was to investigate the regulation of a key
      component of testicular androgen biosynthesis, i.e. the cytochrome P450XVII of
      the steroid-17 alpha-monooxygenase/C17,20-lyase, after surgical induction of
      bilateral cryptorchidism in vivo. Seven days after induction of cryptorchidism,
      P450XVII concentrations are diminished (as compared to sham-operated controls) by
      64% in isolated purified Leydig cells but only by 44% in the total Leydig cell
      compartment of the testis, since the Leydig cell yield from cryptorchid testes is
      by 53% higher than that from control testes. Using microsomal suspensions
      prepared from testicular homogenates, P450XVII content per testis equivalent is
      found to be decreased by 36% seven days after incubation of cryptorchidism,
      whereas the P450XVII concentration per gram testis is not changed due to
      testicular involution. Fourteen days after induction of cryptorchidism, the
      induction of the Leydig cell system appears to superimpose on the down-regulation
      of P450XVII. The study demonstrates both a strong sensitivity of P450XVII to
      short-term elevation of testicular temperature and a differentiation between
      effects of cryptorchidism on total testicular content and specific cellular and
      subcellular concentration of this steroidogenic protein.

PMID- 1981880
TI  - The role of reduced glutathione during the course of acute haemolysis in glucose
      6-phosphate dehydrogenase deficient patients: clinical and pharmacodynamic
      aspects.
AB  - Tissue hypoperfusion leads to cellular oxidative and peroxidative damage due to
      biochemical disorders in the oxygen and substrate metabolism. The metabolic
      turnover of glutathione (GSH) represents one the main cytoprotective systems
      against the peroxide attack and the depletion or defect in resynthesis of this
      compound is accompanied by pathological consequences. In the present study the
      clinical effects of glutathione depletion were investigated in conditions of
      acute tissue hypoxia due to marked haemolysis in glucose-6-phosphate
      dehydrogenase deficient patients (favism syndrome). In these subjects a
      significant marker of the tissue oxidative damage was represented by the uric
      acid blood levels, presumably linked to xanthine-hypoxanthine altered metabolism.
      To antagonize the effects of oxyradical pathology, reduced glutathione was
      administered to a group of patients and the results confirmed the cytoprotective
      role played by the GSH supplementation. The GSH action was evident on the tissue
      metabolism and this supports the opinion that reduced glutathione could represent
      a new and interesting therapeutic approach in marked and acute hypoxic
      conditions.

PMID- 1981879
TI  - Negligible metabolic effects of long-term oral treatment with a new beta 2
      agonist: broxaterol.
AB  - Drugs that stimulate adrenergic receptors are expected to affect glucose and
      lipid metabolism. Therefore, it was deemed to be of interest to assess whether
      the new selective beta 2-adrenoceptor agonist, broxaterol, exerts any metabolic
      effect. Broxaterol has been evaluated in 21 patients, 18 men and 3 women, aged 34
      to 80 years, with a diagnosis of reversible obstructive airways disease.
      Broxaterol was administered orally at doses of 0.5 mg thrice daily for 1-12
      months, according to an open design. In addition to metabolic parameters (plasma
      glucose, insulin, high and low density lipoprotein-cholesterol, triglycerides,
      free fatty acids, glycerol, sodium, potassium), arterial pH, partial arterial
      oxygen and carbon dioxide pressure, lung function tests--forced expiratory volume
      in one second (FEV1), maximum mid-expiratory flow (MMEF75-25) and specific
      airways conductance (SGaw)--heart rate and blood pressure were assessed at
      baseline and after 1, 2, 3, 4, 5, 6, 9, 12 months of treatment. No statistically
      significant change from baseline was observed in the levels of plasma glucose,
      cholesterol, triglycerides, or free fatty acids. Plasma levels of insulin,
      glycerol and sodium only increased in the first three months of treatment; a
      slight hypokalaemia was also observed during the same period. The bronchodilation
      (significant increase in FEV1, MMEF75-25, SGaw) was maintained throughout the
      study; no hospital admission was necessary. Tremor, palpitations and restlessness
      were reported in six patients; no significant changes in heart rate and blood
      pressure were observed. The data suggest that the metabolic effects of long-term
      treatment with oral broxaterol can be considered as very negligible.

PMID- 1981881
TI  - Chemical synthesis of a neurotoxic polypeptide from the sea anemone Stichodactyla
      helianthus.
AB  - The sea anemone Stichodactyla helianthus neurotoxin I, a 48-residue polypeptide,
      was synthesized by automated solid phase methodology. The fully reduced
      polypeptide was subsequently refolded in the presence of a glutathione
      oxidoreduction buffer to the biologically active species containing three
      disulfide bonds. The overall yield after rigorous purification was 12.5%. The
      circular dichroism (CD), and proton nuclear magnetic resonance (1H NMR) spectra
      of the HPLC-purified synthetic toxin were indistinguishable from those obtained
      concurrently with the natural toxin. A subtilisin digest of the synthetic
      neurotoxin generated peptide fragments identical to that of a sample of the
      natural toxin subjected to the same treatment. The toxicity of the synthetic
      polypeptide was identical to that of the natural toxin (crab LD50, 3.1
      micrograms/kg). The equilibrium dissociation constant (28 nM) for interaction of
      the synthetic toxin with crab axolemma vesicles was nearly identical to that of
      the natural toxin (25 nM).

PMID- 1981882
TI  - Synthetic peptides including acidic clusters as substrates of yeast casein kinase
      2.
AB  - The synthesis is reported of a series of glutamyl peptide analogs of the model
      substrate H-Ser-Glu-Glu-Glu-Glu-Glu-OH of casein kinase-2 (CK-2). A convenient
      HPLC method for the separation of slightly different acidic peptides is also
      reported. The site specificity of yeast casein kinase-2 (Y-CK2) is examined with
      the aid of synthesized peptide substrates.

PMID- 1981883
TI  - On the contribution of mathematical models to the understanding of
      neurotransmitter release.

PMID- 1981884
TI  - Potential neurotrophic factors in the mammalian central nervous system:
      functional significance in the developing and aging brain.

PMID- 1981885
TI  - Quinoxalinediones as excitatory amino acid antagonists in the vertebrate central
      nervous system.

PMID- 1981886
TI  - Acquired immune deficiency syndrome and the developing nervous system.

PMID- 1981887
TI  - Single-channel studies of glutamate receptors.

PMID- 1981888
TI  - Genome evolution in the mosquitoes and other closely related members of
      superfamily Culicoidea.
AB  - Karyotypes and nuclear DNA amounts of 36 species belonging to twelve genera of
      mosquitoes and other closely related taxa in the superfamily Culicoidea (Dixidae,
      Chaoboridae, and Culicidae) were studied. The results showed an eight-fold range
      in haploid DNA amounts and a 4.5-fold range in total chromosomal lengths. It is
      concluded that the evolutionary trend in this superfamily has been an overall
      increase in total haploid DNA amounts from the primitive Dixidae to the highly
      evolved Culcidae, with a concomitant increase in overall chromosome sizes.

PMID- 1981890
TI  - High-performance liquid chromatographic assay of dilevalol, a beta-adrenoceptor
      blocker, in rat and human plasma.

PMID- 1981889
TI  - Phenotypic characterization of macrophage subpopulations and localization of
      factor XIII in the stromal cells of carcinomas.
AB  - The infiltration of macrophages both within and at the margin of malignant
      neoplasms can be extensive, but their functions are not well defined. Definitions
      of the antigenic phenotype defined by various monoclonal antibodies may allow
      insight into macrophage function. Single and double immunoenzymatic labelling
      techniques were used to characterize sub-populations of macrophages both within
      and at the margin of breast carcinoma and colorectal carcinoma using a panel of
      antibodies. Factor XIII, previously identified in macrophage cytoplasm, was
      localized at the same sites. Two major groups of tumour-associated macrophages
      were identified; class II MHC+, CD11c+ macrophages predominated within the
      neoplasm, whereas CD14+ macrophages were the major population at the invasive
      margin. Factor XIII+ macrophages were also seen predominantly at the invasive
      margin. Phenotypic variation between macrophage sub-populations may reflect
      functional variation such that macrophages may be beneficial or detrimental for
      neoplastic growth. Factor XIII derived from macrophages may be important in
      stabilization of fibrin deposits associated with the neoplasm.

PMID- 1981891
TI  - Rapid determination of serum oxatomide levels with on-line precolumn solid-phase
      extraction.

PMID- 1981892
TI  - [Drug therapy of intractable Pseudomonas infections].

PMID- 1981893
TI  - Apolipoprotein A-I metabolism in subjects with a PstI restriction fragment length
      polymorphism of the apoA-I gene and familial hypoalphalipoproteinemia.
AB  - Familial hypoalphalipoproteinemia (hypoalpha), characterized by a decreased high
      density lipoprotein level, is associated with an increased incidence of premature
      cardiovascular disease. Restriction fragment length polymorphism analysis of
      genomic DNA has detected a polymorphism for the PstI restriction endonuclease
      near the apoA-I gene, with either a 2.2 or a 3.3 kb fragment. The latter has been
      previously found to occur with significantly higher frequency in probands of
      families with familial hypoalpha. ApoA-I was isolated from three unrelated
      subjects with familial hypoalpha and the 3.3 kb PstI polymorphism of the apoA-I
      gene, and from normal control subjects. The apoA-I from the hypoalpha subjects
      was structurally normal as determined by amino acid analysis and by two
      dimensional gel electrophoresis. When normal apoA-I and hypoalpha apoA-I were
      simultaneously injected into either normal controls or hypoalpha subjects, both
      forms of apoA-I were catabolized at the same rate in the same subject, indicating
      that the hypoalpha apoA-I is also metabolically normal. Analysis of the kinetics
      of metabolism of apoA-I in the hypoalpha subjects, compared to the normal
      controls, revealed that the reduced plasma levels of apoA-I were due to an
      increased apoA-I fractional catabolic rate, and that the synthetic rate was
      normal. Based on these results, we conclude that the apoA-I gene in these
      hypoalpha subjects is normal, and the PstI polymorphism near the apoA-I gene,
      which is associated with familial hypoalpha, is likely to be a marker for a
      mutant gene closely linked to, but not in, the apoA-I gene.

PMID- 1981894
TI  - Purification, and biochemical and structural characterization of a fimbrial
      haemagglutinin of Renibacterium salmoninarum.
AB  - Renibacterium salmoninarum was shown to possess peritrichous fimbriae. Electron
      microscopy of strains FMV 84-01 and ATCC 33209T revealed short, flexible fimbriae
      less than 2 nm in diameter. These surface appendages were isolated from the
      bacteria by a procedure involving water extraction and urea solubilization. The
      fimbrin was purified to homogeneity by Fast Pressure Liquid Chromatography, and
      shown by SDS-PAGE to be a protein of 57 kDa. Isoelectric focusing under non
      denaturing conditions indicated a pI of 4.8. The protein had an amino acid
      composition rich in glycine, Asx (aspartic acid and asparagine), valine and
      alanine; methionine was absent. Approximately 33% of the amino acid residues were
      hydrophobic. Immunoblotting using a polyclonal antiserum raised against whole
      cells showed that the 57 kDa protein was the immunodominant antigen on the cell
      surface. Immunogold labelling using polyclonal antibodies raised against the
      fimbrin revealed an alignment of gold particles along the fimbriae. Purified
      fimbriae caused agglutination of rabbit erythrocytes and antifimbrial serum
      inhibited this haemagglutination. Altogether the results indicate that the
      fimbriae on the surface of R. salmoninarum are responsible for the
      haemagglutinating activity.

PMID- 1981895
TI  - The fimbriae of human enterotoxigenic Escherichia coli strain 334 are related to
      CS5 fimbriae.
AB  - Escherichia coli strain 334 is a human enterotoxigenic strain of serotype O15:H11
      which had previously been shown to produce 'attachment pili'. These fimbriae were
      compared with other colonization factors. From strain 334 a mannose-resistant
      haemagglutination positive colony 334A and a mannose-resistant haemagglutination
      negative variant 334C were isolated. By electron microscopy the fimbriae of
      strain 334A were shown to have a helical structure resembling coli-surface
      associated antigen (CS5) fimbriae. An antiserum was raised to strain 334A and
      absorbed with a fimbriae-negative variant of that strain, 334C. By immuno
      electron microscopy this antiserum was shown to coat fimbriae of strain 334A but
      not CS5 fimbriae produced by strain E17018A. Conversely, CS5 antiserum did not
      coat the fimbriae produced by strain 334A. No antigenic cross-reaction was
      detected between these intact fimbriae when anti-strain 334A serum and CS5
      antiserum were used in immunodiffusion tests. By enzyme-linked immunosorbent
      assays (ELISAs) the fimbriae of strain 334A were shown to be antigenically
      unrelated to most other human ETEC adhesins, namely colonization factor antigens
      (CFA/I, CFA/III and CFA/IV), coli-surface-associated antigens (CS1, CS2, CS3,
      CS4, CS6 and CS17) and putative colonization factors (PCFO159:H4 and PCFO166).
      However, a heated suspension of strain 334A reacted weakly with CS5 antiserum in
      an ELISA. By SDS-PAGE the fimbriae of strain 334A were shown to consist of
      subunits of similar size to CS5 subunits, that is about 21.5 kDa. Western
      immunoblotting revealed that the subunits of 334A and CS5 fimbriae shared common
      epitopes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1981897
TI  - Effect of surface characteristics of theophylline anhydrate powder on hygroscopic
      stability.
AB  - The hygroscopicity of theophylline anhydrate has been investigated by gas
      adsorption and hydration kinetic methods. Type 1 theophylline anhydrate was
      obtained by recystallization from distilled water at 95 degrees C, and type II
      was obtained by dehydration of theophylline monohydrate. The X-ray diffraction
      pattern of types I and II agreed with the data of theophylline anhydrate.
      However, the diffraction peaks of the (200) and (400) planes of type I were much
      stronger than those of type II. The particles of type I were clear crystalline
      like single crystals. However, the particles of type II had many cracks. The gas
      affinity balance (H/N) of type II, measured by gas adsorption, was about 7 times
      that of type I. After the hygroscopicity of types I and II had been tested at
      various levels of relative humidity (RH) at 35 degrees C, type I was stable at
      less than 82% RH, but transformed into the monohydrate at more than 88% RH. Type
      II was stable at less than 66% RH and transformed into the monohydrate at less
      than 75% RH. The hydration data of type I at 88% RH and type II at 75% RH were
      calculated for hydration kinetics using various solid-state kinetic models, but
      no particular model could be preferred from these data.

PMID- 1981898
TI  - Moisture adsorption-desorption effect on the structure of inclusion complex of 6
      chloro-2-pyridylmethyl nitrate and beta-cyclodextrin.
AB  - A new anti-anginal drug, 6-chloro-2-pyridylmethyl nitrate (FR46171), was found to
      form a complex with beta-cyclodextrin (beta-CyD), molecular ratio 1:1. The
      FR46171/beta-CyD complex thus prepared showed a moisture adsorption-desorption
      hysteresis characteristic of hydrophilic polymers. The moisture adsorption
      desorption isotherm and differential scanning calorimetry indicated that the
      moisture adsorbed FR46171/beta-CyD complex includes 13-15 mol of water while the
      moisture desorbed complex includes 5 mol of water. X-ray diffraction patterns of
      these samples confirmed their different structures. The scanning electron
      photomicrographs and the surface areas (BET) suggested that the moisture
      adsorption-desorption hysteresis observed in FR46171/beta-CyD complex can be
      attributed to reversible hydrogen bonding between water molecules and hydroxyl
      groups.

PMID- 1981896
TI  - The effect of solubilized water on the size and shape of lecithin micelles in an
      apolar solvent.
AB  - The changes in the size and shape of the micelles of soya lecithin in
      trichlorotrifluoroethane following the solubilization of increasing quantities of
      water have been examined by dynamic and static light scattering and viscometric
      techniques. Micelles in systems with water/lecithin molar ratios. R. of less than
      2.6 were oblate and exhibited no significant changes in asymmetry or aggregation
      number with changes in the amount of solubilized water. Spherical micelles were
      evident in systems with R = 2.6 whereas prolate micelles were present in
      solutions of higher water content (3.5 less than or equal to R less than or equal
      to 5.2). An increase of R in these systems caused a decrease in the axial ratio
      and an increase in the aggregation number of the micelle.

PMID- 1981899
TI  - Rapidly absorbed solid oral formulations of ibuprofen using water-soluble
      gelatin.
AB  - Rapidly absorbed oral dosage forms of ibuprofen using water-soluble gelatin
      (hydrolysate of common gelatin: mean mol. wt: 6000) have been studied and
      compared with tablets prepared with common gelatin (mean mol. wt: 100,000) and
      commercial tablets. Spray-dried and speed-kneaded powders, two types of granules
      and tablets were prepared with water-soluble gelatin. The in-vitro dissolution
      rates of water-soluble gelatin preparations were significantly faster than those
      of commercial tablets, whereas the tablets prepared using common gelatin had
      slower dissolution rates than commercial tablets. Water-soluble gelatin enhanced
      the dissolution rate of ibuprofen by improving the wettability of the drug
      particle surface by water, without any interaction in solution and the solid
      state. The absorption behaviour of various preparations was evaluated in four
      beagle dogs. The peak concentration time (tmax) of the water-soluble gelatin
      preparations was significantly shorter than that of tablets prepared with common
      gelatin and commercial tablets. The maximum concentration (cmax) and the area
      under the serum concentration-time curve (AUCo-10 h) were similar in all cases.
      The serum concentration profiles of water-soluble gelatin solid preparations were
      almost the same as those of the solutions. On the other hand, the profiles of the
      common gelatin tablets were similar to those of the commercial tablets. The mean
      absorption time (MAT) from water-soluble gelatin preparations was about 0.7 h,
      while the MAT from commercial tablets and common gelatin tablets was about 1.2 h.
      The differences in the MAT of water-soluble gelatin preparations and commercial
      tablets or common gelatin tablets were the same as the differences in mean
      dissolution time (MDT) in gastrointestinal fluid.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1981900
TI  - Changes in intracellular Ca2+ produced in the mouse diaphragm by neuromuscular
      blocking drugs.
AB  - Differences between the effects of depolarizing and competitive neuromuscular
      blocking drugs on Ca2(+)-aequorin luminescences (Ca2+ transients) emitted during
      twitches were compared in indirectly-stimulated diaphragm muscles of mice.
      Succinylcholine enhanced intracellular Ca2+ transients at concentrations of 1.3
      2.5 microM and inhibited them at concentrations of 5.0-50 microM, demonstrating a
      biphasic response as in the case of twitch tensions. However, the response to
      Ca2+ transients was two to three times more sensitive than the response to twitch
      tension. Decamethonium 2.4-96 microM and carbachol 5.5-109 microM produced
      similar results. In contrast, pancuronium and (+)-tubocurarine inhibited them in
      the same concentration ranges. The relation between Ca2+ transients and twitch
      tensions was hyperbolic and was computer-simulated by the Hill equation in the
      case of succinylcholine, decamethonium and carbachol, whereas it was represented
      by a single exponential equation in the case of pancuronium, (+)-tubocurarine,
      and submaximal nerve-stimulation voltage. Spontaneous Ca2+ transients, on the
      other hand, were generated only in response to depolarizing drugs at
      concentrations having a neuromuscular blocking effect. These results suggest that
      depolarizing and competitive neuromuscular blocking drugs affect intracellular
      Ca2+ mobilization by different routes mediated by acetylcholine receptors.

PMID- 1981901
TI  - Evaluation of protein binding effect on local disposition of oxacillin in rat
      liver by a two-compartment dispersion model.
AB  - The effect of protein binding upon the hepatic uptake of oxacillin was evaluated
      in the rat isolated perfused liver, based on the two-compartment dispersion model
      by means of the fast inverse Laplace transform (FILT). The perfusion experiment
      was carried out using the perfusates without and with bovine serum albumin (BSA,
      40 g L-1). Oxacillin was injected as a pulse through the portal vein, and the
      outflow concentration-time course of oxacillin was fitted to the dispersion model
      using the non-linear least squares program MULTI(FILT). The partition ratio (k'),
      which is the measure of the extent of the reversible distribution into the
      hepatic tissue, was 0.163 +/- 0.041 (s.d.) in the presence of BSA, and 0.095 +/-
      0.018 in the absence of BSA, which suggests interaction of the albumin-bound drug
      with the hepatic tissue. The elimination rate constant (ke) from the perfusate in
      the absence of BSA was 8.0 +/- 0.55 min-1 and that in the presence of BSA was 3.3
      +/- 1.4 min-1 while the unbound fraction of the drug in the presence of 40 g L-1
      BSA was 0.282. The hepatic elimination rate of oxacillin was not proportional to
      the unbound concentration of drug suggesting hepatic uptake of the bound
      fraction.

PMID- 1981902
TI  - Microcalorimetric study for the binding of ionic drugs to human erythrocytes and
      the ghost membranes.
AB  - The binding of phenothiazine derivatives (as cationic drugs) and non-steroidal
      anti-inflammatory drugs (as anionic drugs) to human erythrocytes and ghost
      membranes has been compared with respect to their thermodynamic characteristics,
      by flow microcalorimetry at pH 7.4 and 37 C. From enthalpyentropy correlation, it
      was shown that anionic and cationic drugs are bound to different binding sites on
      the membranes. Phenothiazines bind to a single common site of the erythrocyte
      membranes with relatively high binding affinities (K = 10(4)-10(5) M-1). The
      binding is entropy-driven and characterized by a small negative enthalpy (delta
      H) and a positive entropy change (delta S), reflecting hydrophobic interactions.
      However, the binding reaction for the intact erythrocytes shows large negative
      values for both delta H and delta S. The values of K for the membranes and delta
      H for the intact erythrocytes increased with the increase of the hydrophobic
      character of the substituent group at the C-2 position of the phenothiazine
      nucleus (H less than Cl less than CF3). The results indicate that phenothiazines
      bind and or penetrate to the inner membranes of the erythrocytes and react with
      intracellular components such as haemoglobin, while anti-inflammatory drugs bind
      to the surface protein on the membranes with a lower affinity (K = 10(3) M-1)
      than phenothiazines, reflecting the small negative delta H and positive delta S
      for the interaction with intact erythrocytes.

PMID- 1981903
TI  - Cerebral pharmacokinetics of ipsapirone in rats after different routes of
      administration.
AB  - Ipsapirone, a putative non-benzodiazepine anxiolytic, was extensively metabolized
      in rats to 1-(2-pyrimidinyl)piperazine (1-PP) which accumulated in the brain.
      Neither the route of administration (i.p. or p.o.), nor prolonged administration
      of ipsapirone or 1-PP affected their accumulation in the rat brain. The
      cytochrome P450 level and ethylmorphine N-demethylase activity in rat liver
      microsomes were unchanged by chronic treatment with ipsapirone or 1-PP. The
      results indicate that 1-PP may contribute to the alpha 2-adrenoceptor antagonism
      of ipsapirone in rats and that chronic treatment with the drug does not affect
      its biotransformation to 1-PP.

PMID- 1981904
TI  - The preservation of functional activity of smooth muscle and endothelium in pig
      coronary arteries after storage at -190 degrees C.
AB  - Pig coronary arteries have been investigated in-vitro using fresh tissue or after
      storage at -190 C in foetal calf serum containing 1.8 M dimethyl sulphoxide.
      Attention was paid to modulation of contractile activity and endothelium
      dependent relaxation. After cryopreservation of the arteries maximal contractile
      responses to both 5-hydroxytryptamine (5-HT) and prostaglandin F2 alpha (PGF2
      alpha) were markedly reduced and the pD2 values for both agonists were slightly,
      but significantly, diminished. Nevertheless, 5-HT antagonism by ketanserin and
      pizotifen was unchanged. Endothelium-independent relaxant responses of
      precontracted arteries to isoprenaline, forskolin, 3-isobutyl-1-methylxanthine,
      nitroprusside, atriopeptin III and cromakalim were generally unchanged after
      storage. Mechanical removal of the endothelium by rubbing enhanced the
      contractile response to PGF2 alpha in both fresh and stored arteries to a similar
      extent. In addition, endothelium-dependent relaxant responses to both 5-HT and
      substance P were well maintained, suggesting release of endothelium-derived
      relaxing factor by the stored arteries. The evidence suggests that after
      cryopreservation of pig coronary arteries at -190 degrees C mechanisms of
      relaxation, in particular those which are endothelium-dependent, are well
      maintained.

PMID- 1981905
TI  - The effects of oral administration of (-)-menthol on nasal resistance to airflow
      and nasal sensation of airflow in subjects suffering from nasal congestion
      associated with the common cold.
AB  - The effects of oral administration of a lozenge containing 11 mg (-)-menthol on
      nasal resistance to airflow (NAR) and nasal sensation of airflow in 62 subjects
      suffering from nasal congestion associated with naturally acquired common cold
      infection have been studied. NAR was measured by posterior rhinomanometry and
      nasal sensation of airflow by means of a visual analogue scale (VAS). The effects
      of the lozenge were compared with a candy placebo lozenge in a double blind
      randomized trial. NAR showed a significant increase (P less than 0.05) in both
      the menthol and placebo groups over the 2 h experiment with no difference between
      the groups at any time. The VAS scores showed significant changes of subjective
      improvement in nasal sensation of airflow (P less than 0.001) in the menthol
      treated group 10 min after dosing whereas the placebo group showed no change. It
      is concluded that dosing with 11 mg menthol in subjects with common cold has no
      effect on NAR as measured by posterior rhinomanometry but causes a marked change
      in nasal sensation of airflow with a subjective sensation of nasal decongestion.

PMID- 1981907
TI  - Effect of zinc sulphate on acetic acid-induced gastric ulceration in rats.
AB  - The effects of zinc sulphate on gastric ulcer healing rate and mucosal mucus
      content of acetic acid-induced ulceration in rats have been assessed. Daily
      treatment with zinc sulphate progressively accelerated ulcer healing in a dose
      dependent manner with a significant increase observed on day 15 after ulcer
      induction in rats treated with 44 and 88 mg kg-1 zinc sulphate. A significant
      increase in gastric mucosal adherent mucus was also observed in those animals
      treated with 88 mg kg-1 zinc sulphate. The results suggest that a minimum
      treatment period of 15 days is needed for the zinc sulphate to be effective, and
      that zinc ions may promote gastric ulcer healing by enhancing mucus formation to
      prevent acid back-diffusion into the gastric mucosa.

PMID- 1981906
TI  - Potent inhibition of prostaglandin inactivation in rabbit gastric antral mucosal
      slices by selenium ions in-vitro.
AB  - The effect of selenium ions on prostaglandin (PG) catabolism and synthesis in
      rabbit gastric antral mucosal slices has been examined. Selenium ions had a
      potent inhibitory effect on the inactivation process for PGE2 and PGF2 alpha.
      Simultaneously, the levels of PGE2 and PGF2 alpha were increased. These results
      suggest that selenium ions have the potential to increase the levels of
      biologically active PGs in gastric mucosa by preventing their inactivation and
      that this effect may represent some pharmacological action of selenium ions.

PMID- 1981908
TI  - Polyphloretin phosphate (PPP) antagonists of prostaglandin action also inhibit
      prostaglandin biosynthesis in-vitro.
AB  - Several polyphloretin phosphate (PPP) fractions (low mol. wt LC1259; high mol. wt
      LC1261; crude mixture, LC101) were confirmed in their established property as
      antagonists of the pharmacological actions of prostaglandins in a preparation of
      guinea-pig isolated ileum stimulated by prostaglandin (PG)E2. Further samples of
      the same material were then compared in-vitro with indomethacin in their ability
      to inhibit prostaglandin biosynthesis from arachidonic acid by a microsomal
      enzyme preparation. All three PPP fractions potently inhibited prostaglandin
      generation, with the rank order of potency LC1259 = LC101 = indomethacin greater
      than LC1261. The oral LD50 in mice was 25 mg kg-1 for indomethacin and greater
      than 1 g kg-1 for LC101. PPP fractions (especially LC101) may therefore have
      therapeutic potential as anti-inflammatory agents.

PMID- 1981910
TI  - Negative inotropic effect induced by diethylamiloride (DEA) in rabbit myocardium.
AB  - The effects of the Na+/H+ exchange blocking drug diethylamiloride (DEA) on
      mechanical function have been studied in the rabbit isolated, arterially perfused
      interventricular septum. At concentrations of 10(-6)-10(-5) M, DEA induced a
      significant, dose-dependent, negative inotropic effect (a 54% decrease from
      control values at the highest concentration), which was slow to develop. After a
      45 min washout, recovery was almost complete (95 +/- 3.4%). At concentrations
      greater than 5 x 10(-5) M, DEA induced a rapid and marked decrease in developed
      tension, associated with a progressive decrease in excitability and incomplete
      recovery. Resting tension was not significantly modified at any of the
      concentrations tested. At greater than 10(-6) M DEA enhanced significantly the
      transient negative inotropic effect of the brief intracellular acidosis induced
      by removal of NH4Cl perfusion, both by decreasing the minimal value of developed
      tension and by increasing the time required to produce this effect. These effects
      suggest that the dose-dependent DEA negative inotropic effect could be mediated
      by a progressive intracellular acidosis produced by inhibition of the Na+/H+
      exchange system.

PMID- 1981911
TI  - Ketamine as an anaesthetic in dogs.

PMID- 1981909
TI  - Cortisone: a potent GABAA antagonist in the guinea-pig isolated ileum.
AB  - In the guinea-pig isolated ileum, cortisone at 0.001-10 nM induced a non
      competitive, dose-dependent antagonism of GABAA-receptor-mediated contractile
      responses to applied GABA, depressing the maximum contractile response to GABA
      (100 microM), without affecting contractile responses to acetylcholine or
      cholinergic twitch contractions. At higher concentrations (greater than 10 nM),
      cortisone depressed contractile responses to acetylcholine (10-100 nM) and
      cholinergic twitch responses to transmural stimulation. Cortisone is thus the
      most potent non-competitive antagonist at GABAA-receptor complexes in the guinea
      pig ileum. From molecular modelling, sterically there appeared little difference
      between cortisone and cortisol, the latter being an enhancer of GABAA-receptor
      mediated action in the ileum. However, there were significant differences in
      electrostatic potentials between the two steroids, due to the different levels of
      oxidation at C11 which may contribute to such opposing actions.

PMID- 1981912
TI  - Simultaneous determination of sulfasalazine and its metabolites sulfapyridine and
      N-acetylsulfapyridine in human serum by ion-pair high-performance liquid
      chromatography using a polymer-based column.
AB  - An HPLC method is described for the simultaneous and rapid determination of
      sulfasalazine (salicylazosulfapyridine) and two of its metabolites, sulfapyridine
      and N-acetylsulfapyridine, in human serum. The range of quantitation is 0.1 to 12
      micrograms/mL for sulfasalazine and sulfapyridine and 0.25 to 12 micrograms/mL
      for N-acetylsulfapyridine. Serum is mixed with acetonitrile containing the
      internal standard sulfamethazine and the ion-pairing agent tetraethylammonium
      chloride. The acetonitrile extract is concentrated and analyzed by HPLC, using a
      new polymer-based column, and detected by UV spectroscopy at 270 nm. This paper
      is the first both to describe the simultaneous analysis of all three of the
      compounds from serum and to present sulfasalazine concentration-time data
      following oral administration to humans.

PMID- 1981913
TI  - Inhibition of neurotransmitter release by botulinum neurotoxins and tetanus toxin
      at Aplysia synapses: role of the constituent chains.
AB  - 1. The effects on the release of transmitter by botulinum neurotoxins (BoNT;
      types A, B, E), tetanus toxin (TeTx), constituent chains or fragments were
      studied on identified cholinergic and non-cholinergic synapses in Aplysia. 2.
      Cholinergic synapses in the buccal ganglion were found to be greater than 100
      fold more sensitive to extracellular application of BoNT than to TeTx whereas in
      non-cholinergic synapses of the cerebral ganglion the potencies of the toxins
      were reversed. When intracellularly applied TeTx and BoNT were found nearly
      equipotent. This disparity in the susceptibilities of BoNT and TeTx to inhibit
      transmission was attributed to differences in the toxin's acceptors or uptake
      systems in the two neurone types. 3. Micro-injection into cholinergic neurones of
      the isolated renatured toxins' chains showed that both light and heavy chains of
      BoNT are intracellularly required whereas the light chain of TeTx alone is
      sufficient. 4. The heavy chain of BoNT as well as that of TeTx were found to
      mediate internalization of active moieties via its amino-terminal half.
      Furthermore the heavy chain of one toxin could internalize the light chain of the
      other.

PMID- 1981914
TI  - A topological model of the NMDA-glycine receptor model.

PMID- 1981915
TI  - PET demonstrates different behaviour of striatal dopamine D-1 and D-2 receptors
      in early Parkinson's disease.
AB  - Striatal dopamine D-1 receptor binding was investigated in vivo with positron
      emission tomography (PET) in five patients with early Parkinson's disease using
      [11C]-SCH 23390. All patients had predominantly unilateral symptoms and showed a
      significant reduction in the accumulation of [18F]-6-F-DOPA in the striatum
      contralateral to the symptoms. None of the patients had received any
      antiparkinsonian medication. The striatal and cerebellar radioactivity was
      measured and corresponding striatum/cerebellum ratios were counted. The mean
      striatum/cerebellum ratio of [11C]-SCH 23390 binding was symmetric between the
      hemispheres. By contrast, the striatum/cerebellum ratio of [11C]raclopride
      binding, labelling dopamine D-2 receptors, was increased significantly in the
      hemisphere contralateral to the symptoms as compared with the opposite
      hemisphere. Thus, the present results show that the behaviour of striatal D-1 and
      D-2 receptors is different in early Parkinson's disease.

PMID- 1981916
TI  - Quisqualate- and NMDA-sensitive [3H]glutamate binding in primate brain.
AB  - Excitatory amino acids (EAA) such as glutamate and aspartate are probably the
      neurotransmitters of a majority of mammalian neurons. Only a few previous studies
      have been concerned with the distribution of the subtypes of EAA receptor binding
      in the primate brain. We examined NMDA- and quisqualate-sensitive [3H]glutamate
      binding using quantitative autoradiography in monkey brain (Macaca fascicularis).
      The two types of binding were differentially distributed. NMDA-sensitive binding
      was most dense in dentate gyrus of hippocampus, stratum pyramidale of
      hippocampus, and outer layers of cerebral cortex. Quisqualate-sensitive binding
      was most dense in dentate gyrus of hippocampus, inner and outer layers of
      cerebral cortex, and molecular layer of cerebellum. In caudate nucleus and
      putamen, quisqualate- and NMDA-sensitive binding sites were nearly equal in
      density. However, in globus pallidus, substantia nigra, and subthalamic nucleus,
      quisqualate-sensitive binding was several-fold greater than NMDA-sensitive
      binding. In thalamus, [3H]glutamate binding was generally low for both subtypes
      of binding except for the anterior ventral, lateral dorsal, and pulvinar nuclei.
      In the brainstem, low levels of binding were found, and strikingly the red
      nucleus and pons, which are thought to receive glutamatergic projections, had
      approximately 1/20 the binding observed in cerebral cortex. These results
      demonstrate that NMDA- and quisqualate-sensitive [3H]glutamate binding are
      observed in all regions of primate brain, but that in some regions one subtype
      predominates over the other. In addition, certain areas thought to receive
      glutamatergic projections have low levels of both types of binding.

PMID- 1981917
TI  - Neurotransmitter changes in Alzheimer's disease: implications to diagnostics and
      therapy.
AB  - Changes in the cholinergic, serotonergic, noradrenergic, dopaminergic, GABAergic
      and somatostatinergic neurons were investigated to determine their roles in
      Alzheimer's disease (AD). Markers for these systems were analyzed in postmortem
      brain samples from 20 patients with AD and 14 controls. In the CSF study, markers
      for the cholinergic neurons (choline esterase, ChE) and for the somatostatinergic
      neurons (somatostatin-like immunoreactivity, SLI) were assayed for 93 and 75
      probable AD patients and 29 and 19 controls, respectively. Activity of choline
      acetyltransferase (CAT) was decreased by 50-85% in four cortical areas and
      hippocampus in patients with AD, but not in other areas of the brain, indicating
      a profound deficit in the function of cholinergic projections ascending from the
      nucleus basalis to the cerebral cortex and hippocampus in AD. Muscarinic receptor
      binding was reduced by 18% in the frontal cortex but not in other areas of the
      brain in AD. Serotonin (5HT) concentrations were reduced (by 21-37%) in
      hippocampal cortex, hippocampus and striatum; and 5HT metabolite levels were
      lowered (by 39-54%) in three cortical areas, thalamus and putamen in AD patients.
      Concentrations of noradrenaline (NA) were reduced (18-36%) in frontal and
      temporal cortex and putamen. These data imply that serotonergic and noradrenergic
      projections are also affected in AD but less than the cholinergic neurons.
      Dopamine (DA) concentrations in AD patients were reduced by 18-27% in temporal
      and hippocampal cortex and hippocampus, while HVA, the metabolite of DA, was
      unaltered. Glutamic acid decarboxylase activity was not altered in AD. SLI was
      decreased (28-42%) in frontal, temporal and parietal cortex, but not in thalamus
      and putamen in patients with AD. Frontal tangle scores correlated most strongly
      with cortical CAT activity reduction and less so with decreases of 5HT, NA and
      DA, indicating a closer correlation with the cholinergic changes and severity of
      AD than with other neurotransmitter deficiencies. ChE activity and SLI were
      reduced by 20% and 35%, respectively, in CSF of the whole group of AD patients as
      compared to the controls. Comparison of CSF findings between four subgroups of
      dementia severity indicated that the SLI was already reduced in the group of
      mildest AD (-31%), while ChE activity was not. Although ChE activity in CSF
      declined in relation to dementia severity, however, the maximal reduction was
      only modest (-30%). On the other hand, SLI in CSF showed only a slight further
      reduction (up to -41%) as the dementia become more severe.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 1981918
TI  - Renal brushborder membrane vesicle. Study of marker enzymes and uptake of
      nutrients in Mycobacterium leprae infected mice.
AB  - The renal brush border membrane vesicles (BBMV) were used to elucidate the early
      biochemical functional status during the course of experimental M. leprae
      infection in mice. The activities of the characteristic brush-border enzymes viz:
      alkaline phosphatase, leucine amino peptidase and gamma-glutamyl transpeptidase
      were found to be significantly decreased (p less than 0.001) at 3 and 6 months
      after infection. The transport of nutrients viz: D-glucose, L-alanine, L-lysine
      and L-aspartate across BBMV showed similar pattern. The activity of brush border
      enzymes and transport of nutrients across the membrane returned to normal at 9
      months post-infection suggesting regeneration of the brush border membrane.

PMID- 1981919
TI  - No major defect detected in the gene of familial hypo-retinol-binding
      proteinemia.
AB  - Retinol-binding protein (RBP), a plasma protein with a molecular weight of 21,000
      daltons, binds to retinol with a 1:1 molar ratio and transports it to the
      peripheral tissues. Familial hypo-retinol-binding proteinemia (hypo-RBPnemia) was
      detected in a 2-year-old girl who developed keratomalacia, and in her mother and
      sister. They persistently showed half the normal levels of RBP and retinol.
      Restriction fragments of leukocyte DNA, created by digestion with BamHI, EcoRI
      and PstI when human RBP complementary DNA was used as a probe, showed the same
      patterns in both the affected and unaffected family members. These results
      indicate that familial hypo-RBPnemia could be attributed to such minor changes as
      point mutations, rather than large deletion or insertion in the RBP gene.

PMID- 1981920
TI  - Restriction fragment length polymorphisms among Japanese detected with a
      dihydropteridine reductase cDNA gene probe.
AB  - Using a human dihydropteridine reductase (DHPR) cDNA, the frequency of
      restriction fragment length polymorphisms (RFLPs) with restriction endonucleases
      AvaII, MspI, NcoI and HinfI was estimated in unrelated, unaffected Japanese. The
      allele frequencies are different from those found in Caucasians, especially with
      MspI and HinfI. However, approximately 60% of Japanese are heterozygous for at
      least one of the RFLPs and analysis of one family with DHPR deficiency was shown
      to be informative. RFLP linkage analysis will be useful in the Japanese
      population as previously reported for Caucasians.

PMID- 1981921
TI  - Prenatal exclusion of ornithine transcarbamylase (OTC) by using RFLP analysis.

PMID- 1981923
TI  - The optic nerve. Padua, Italy, November 1988.

PMID- 1981922
TI  - [The H2-antagonist therapy withdrawal syndrome: the possible role of
      hyperprolactinemia].
AB  - Patients previously treated with H2-receptor blocking agents (cimetidine or
      ranitidine) exhibited a complex neurobehavioral and gastroenteric syndrome,
      including anxiety, insomnia, anorexia, growing thin, irritability, tachycardia,
      diarrhoea, nausea, vomiting, abdominal pain, headache, vertigo. These symptoms
      were dramatically reduced by administration of cimetidine or ranitidine, and
      reappeared with a new suspension of the therapy. The withdrawal syndrome from H2
      receptor antagonists was reversed by treatment with domperidone (10 mg three
      times per day), a potent hyperprolactinaemic drug which does not cross the blood
      brain barrier. These results suggest that the drop in prolactin levels that
      occurs when cimetidine or ranitidine are suspended may contribute to the
      development of the withdrawal syndrome.

PMID- 1981924
TI  - Global warfare against AIDS, report on the Sixth International Conference on
      AIDS, San Francisco, California, 20-25 June, 1990.
AB  - Reports of AIDS cases continue to increase in all countries. Heterosexual
      transfer is on the rise with subsequent implications for maternity care. Young
      men and women at the beginning of their sexual lives are at great risk for HIV
      exposure since unprotected sexual intercourse is rampant. Behaviour changes are
      necessary. Society is charged to indiscriminately care for all of its members.
      Legal protection for people with AIDS is necessary. Orphans, mothers and families
      need special assistance. The challenge has been made. History will determine our
      success.

PMID- 1981925
TI  - The role of medication in falls among the elderly in a long-term care facility.
AB  - This case-control study examines the relationship between falls and drug use in
      elderly residents of a long-term care facility. The drug use and functional
      status of 57 first-time fallers were compared retrospectively with those of 90
      residents who had never fallen. Fallers were taking significantly more drugs than
      controls. Hypnotic/anxiolytics and cardiac drugs carried a twofold increase in
      the risk of falling. Fallers were restrained less often, were more often
      ambulatory, and had been at the institution for a shorter time than controls.
      Previous studies have failed to use control groups or have selected controls by
      length of stay, possibly introducing bias into the results. A large prospective
      study is needed to determine whether these results are generalizable to the
      elderly institutionalized population as a whole.

PMID- 1981926
TI  - Effect of partial removal of frontal or parietal bone on concentrations of mRNAs
      coding for preprocholecystokinin and preprosomatostatin in rat neocortex.
AB  - Partial removal of the frontal or parietal bone increased concentrations of mRNAs
      coding for preprocholecystokinin and preprosomatostatin in rat parietotemporal
      cortex by more than 170 and 67%, respectively, when measured 3 days after the
      operation. The increases were independent of the anaesthetic agent used during
      the operation and were transient with a maximum usually observed 3 days after the
      operation. They occurred not only in areas close to or under the removed bone
      part, but also in more distant areas. Thus, removal of the frontal bone also
      enhanced levels of preprocholecystokinin- and preprosomatostatin-mRNA in the
      parietotemporal and occipital cortex. mRNA concentrations were increased in the
      inner as well as outer layers of the cortex. The possible experimental and
      pathophysiological implications of the observed changes in gene expression of
      both neuropeptides in neocortical neurons are discussed.

PMID- 1981929
TI  - Salivary complaints: a manifestation of depressive mental illness.

PMID- 1981928
TI  - Role of delta opioid receptors in the effects of inhibitors of enkephalin
      degrading peptidases on the horizontal and vertical components of locomotion in
      mice.
AB  - In the present study we report the effects of inhibitors of enkephalin-degrading
      peptidases on spontaneous locomotion in mice and the involvement of delta opioid
      receptors in these effects. Animals received intracerebroventricularly (i.c.v.)
      or intravenously (i.v.) enkephalinase inhibitors (thiorphan and acetorphan),
      aminopeptidase inhibitors (bestatin and carbaphethiol) or mixed peptidase
      inhibitors (kelatorphan). The i.c.v. co-administration of bestatin and thiorphan
      (50 micrograms + 50 micrograms) induced an increase in both the horizontal and
      vertical components of locomotion. A similar pattern was observed after the
      i.c.v. administration of kelatorphan (8.5-50 micrograms) or the i.v. co
      administration of acetorphan and carbaphethiol (5 mg/kg + 10 mg/kg). The opiate
      antagonist naltrexone (1 mg/kg, s.c.) failed to reverse the excitolocomotor
      effects of kelatorphan or of bestatin and thiorphan and antagonized only
      partially the effects of acetorphan and carbaphethiol. Naloxone (2 mg/kg-10
      mg/kg, s.c.) partially reversed the increase in locomotion elicited by bestatin
      and thiorphan. The pretreatment with the delta opioid antagonists ICI 154,129 (20
      micrograms, i.c.v.) or ICI 174,864 (2-4 micrograms, i.c.v.) strongly decreased
      the effects of all the peptidase inhibitors we tested. These results suggest that
      endogenous enkephalins may control via delta opioid receptors the horizontal and
      vertical components of locomotor activity in mice.

PMID- 1981927
TI  - Proopiomelanocortin (POMC)-derived peptides and sleep in the rat. Part 1-
      Hypnogenic properties of ACTH derivatives.
AB  - The sleep-wake effects of the proopiomelanocortin (POMC)-derived peptides, i.c.v.
      injected, are reported. Adrenocorticotropic hormone (ACTH, 1 microgram) induces
      an awakening effect, while its two derivatives, desacetyl-alpha-MSH (des-alpha
      MSH, 1ng) and corticotropin-like intermediate lobe peptide (CLIP, 10 ng), are
      respectively able to increase slow wave sleep (SWS) and paradoxical sleep (PS);
      the hypnogenic effect of CLIP is also observed in hypophysectomized rats.
      Furthermore, two hypothalamic factors known to be involved in the control of POMC
      derivatives were also injected; MSH inhibiting Factor (MIF) does not influence
      the vigilance states, while Corticotropin Releasing Factor (CRF, 1 microgram)
      increases the waking state. Finally, some preliminary results, obtained with a
      restraint stress and suggesting a possible interrelation between stress, sleep
      and POMC derivatives, are discussed.

PMID- 1981930
TI  - [Changes in the sensitivity of the central nervous system to fenazepam at
      different stages of the recovery period after systemic circulatory arrest in
      rats].
AB  - Chronic experiments were conducted on rats subjected to 10-minute circulatory
      arrest to study the effect of intraperitoneal phenazepam (2 mg/kg) injection in
      various periods after resuscitation on some behavior indices. It was found that
      the changes in the quantitative (the degree of the effect) and qualitative (the
      extent of the effect) manifestations of the tranquilizing effect of phenazepam
      were determined by the different stages of restoration (from 1 to 21 days) after
      resuscitation. The results provide evidence of a definite stage character in the
      reactivity of the central nervous system in relation to pharmacological effects
      after resuscitation and, possibly, may reflect the functional reorganization of
      the work of the receptor complex and ion conductivity in the postresuscitation
      period.

PMID- 1981931
TI  - [The changes in the enzymatic activity of glutathione metabolism in
      immobilization stress and their possible significance].
AB  - Immobilization of rats for 20 minutes and for 4 hours activates glutathione
      peroxidase in the heart, liver, and kidneys and glutathione transferase in the
      heart and liver, but inhibits gamma-glutamyl transferase in the liver and
      kidneys. Most of these changed values become normalized one hour after cessation
      of 4-hour stress. Propranolol completely prevents activation of glutathione
      peroxidase and glutathione transferase by stress. The changes in the activity of
      the glutathione metabolism enzymes are evidently of a protective character in
      relation to lipid peroxidation.

PMID- 1981932
TI  - [Liver function in patients with pulmonary tuberculosis and alcoholism].

PMID- 1981933
TI  - [Effect of thymic immunomodulators on the system of cyclic nucleotides of splenic
      T-lymphocytes after BCG vaccination].
AB  - The experiments on guinea pigs was performed to study the effects of thymogen ,
      thymalin and vilosene on the activity of cAMP, cGMP, adenylate cyclase, guanylate
      cyclase, cAMP- and cGMP-phosphodiesterases in T lymphocytes during BCG
      vaccination. It was shown that the disease was accompanied by increased activity
      of enzymes of anabolism and catabolism of cyclic nucleotides. Thymogen and
      thymalin mainly activated the synthesis of cGMP, thus causing the shift of
      cAMP/cGMP value below the reference level. At the same time vilosene increased
      this value in the process of a repeated BCG injection.

PMID- 1981934
TI  - Growth promotion in farm animals.

PMID- 1981935
TI  - Variable-interval schedules of timeout from avoidance: effects of anxiolytic and
      antipsychotic drugs in rats.
AB  - Concurrent performances were studied in rats under conditions where responses on
      one lever postponed shock on a Sidman avoidance schedule and responses on another
      lever produced periods of signaled timeout from avoidance on a variable-interval
      schedule. Chlorpromazine decreased rates of responding on both the timeout and
      avoidance levels to about the same extent. The effects of chlordiazepoxide and
      CGS 9896 depended upon the event maintaining responding. Both drugs increased
      responding on the timeout lever at doses that concurrently decreased responding
      on the avoidance lever. Thus, the novel anxiolytic CGS 9896 produced effects that
      closely resembled those of the benzodiazepine anxiolytic, chlordiazepoxide. Like
      chlorpromazine, buspirone decreased both avoidance and timeout responding.
      Despite the documented anxiolytic properties of buspirone, its actions here were
      unlike those of the other anxiolytic drugs tested. Nonetheless, the
      differentiation between drugs obtained with the timeout from avoidance procedure
      indicates its utility for behavioral pharmacology.

PMID- 1981936
TI  - The D2 agonist quinpirole potentiates the discriminative stimulus effects of the
      D1 agonist SKF 38393.
AB  - Although there are two dopamine (DA) receptors (D1 and D2) in the brain, the
      functional role, particularly of D1 receptors, has remained unclear. Recent
      research has suggested that D1 and D2 receptors interact synergistically in the
      generation of certain D2 agonist-induced motor responses. On the other hand, an
      antagonistic interaction between the receptors has been reported for D1 agonist
      induced perioral movements. The purpose of the present experiment was to
      characterize further the interaction between D1 and D2 receptors using a drug
      discrimination paradigm, a behavioral paradigm that is sensitive and selective
      for D1 and D2 agonist and antagonist activity. Rats (N = 8) were trained to
      discriminate the D1 agonist SKF 38393 (SKF; 10 mg/kg, IP, 30 minutes presession)
      from saline (1.0 ml/kg, IP, 30 minutes presession) in a 2-lever, food-reinforced
      drug discrimination paradigm, SKF (0.2-12.8 mg/kg) produced a dose-related
      increase in SKF-appropriate responding (maximum 87.5% at 12.8 mg/kg). The D2
      agonist quinpirole (QUIN; 0.012-0.1 mg/kg, IP, 10 minutes presession) given alone
      did not substitute for SKF (maximum 37% SKF-appropriate responding at 0.05
      mg/kg). QUIN (0.012 or 0.025 mg/kg) in combination with SKF significantly (p less
      than 0.05) shifted the SKF dose-response function to the left, suggesting that
      stimulation of D2 receptors can potentiate a behavioral effect mediated by D1
      receptors. Furthermore, when taken together with previous findings that SKF
      failed to potentiate the discriminative stimulus effects of QUIN, the present
      results suggest that the nature of D1/D2 receptor interactions depends not only
      upon the behavior under investigation but also upon the receptor action that the
      behavior reflects.

PMID- 1981937
TI  - 5-HT1A agonist effects on punished responding of squirrel monkeys.
AB  - Buspirone and other drugs that act as 5-HT1A agonists appear to be clinically
      effective anxiolytics in humans, yet their anticonflict effects, though robust in
      pigeons, are equivocal in rodents. In the present study we examined the effects
      of the benzodiazepine midazolam and a series of 5-HT1A agonists on punished
      responding of squirrel monkeys. Lever presses were reinforced according to a
      fixed-interval 3-min schedule; in addition, each thirtieth lever press was
      punished. Midazolam produced large increases in response rates, whereas none of
      the 5-HT1A compounds produced any increases in responding. Most of these drugs
      decreased response rates at the higher doses examined. Although the reasons for
      the discrepancy between species in the anticonflict effects of serotonergic
      anxiolytics cannot be specified, the different anatomical distribution of 5-HT1A
      binding sites across species may suggest a different functional role for this
      receptor.

PMID- 1981938
TI  - Cocaine produces cholinergically mediated analeptic and EEG arousal effects in
      rabbits and rats.
AB  - Cocaine (1-5 mg/kg, IV) shortened the duration of loss of righting reflex
      produced in pentobarbital-narcotized rabbits. This effect was completely blocked
      by scopolamine (1 mg/kg, IV), but not by scopolamine methylbromide, suggesting
      that a central cholinergic mechanism was involved. In urethane-anesthetized rats
      cocaine (1 mg/kg, IV) consistently generated hippocampal EEG theta rhythm lasting
      about 40 min. This effect was also abolished by scopolamine. These results
      suggest that cocaine produced behavioral and EEG arousal responses that involved
      the septohippocampal cholinergic system.

PMID- 1981939
TI  - Cytochemical markers of neural and endocrine cells. XXX. Symposium of the
      International Association of Histochemists. Gargellen, Austria, September 21-24,
      1988. Proceedings.

PMID- 1981940
TI  - Ultrastructure of the dynorphin-immunoreactivity in rat brain hippocampal mossy
      fiber system.
AB  - In rat hippocampus, the opioid peptide dynorphin A (1-17) is present in a
      subpopulation of the mossy fiber terminals, as shown by ultrastructural
      immunocytochemistry. The immunoreactive boutons exhibit all features
      characteristic for giant mossy fiber boutons, as e.g. inclusions of neighboring
      giant boutons which may or may not be dynorphin A-positive. At early survival
      times after selective lesioning the mossy fiber system with colchicine, lysosomes
      indicative for the proceeding degeneration are present in boutons still
      immunoreactive for dynorphin A as well as in non-immunoreactive boutons. This
      observation provides evidence that the dynorphinergic terminals are in fact the
      endings of the granule cells.

PMID- 1981941
TI  - Transglutaminase immunoreactivity in the male genital tract of the rat.
AB  - The distribution of transglutaminase immunoreactivity in the male genital system
      of the rat has been studied at the light and electron microscopic levels using a
      highly specific polyclonal antibody. The antibody is obviously secreted in an
      apocrine fashion in the dorsal prostate as well as the coagulating gland. This
      moiety is responsible for semen clotting. In addition to the secretory moiety,
      epididymal sperm contain endogenous immunoreactive material in the cytoplasmic
      droplet. Whether this is added to the sperm within the epididymis--as is the
      immunoreactive material on the sperm head--or already present in developing sperm
      has to be elucidated by further immunoelectron microscopic studies.

PMID- 1981942
TI  - [Chromogranins in endocrine cells of the digestive system].

PMID- 1981943
TI  - Structural comparison of assemblies from brain microtubule proteins of different
      vertebrates.
AB  - Formerly, we reported for microtubule protein (MTP), i.e. tubulin plus
      microtubule-associated proteins (MAPs), from porcine brain that the protofilament
      number of microtubules and the percentage of aberrant assemblies depend on taxol
      and MAP activity (Bohm et al., BBA 800, 119, 1984). Now, it is demonstrated that
      these effects can be also observed when MTPs from other higher vertebrate brains
      (Guinea pig, mouse chicken) were used. Comparing the structural features of
      assemblies formed from these kinds of MTP with each other no significant
      differences were found, excepted chicken MTP which produces more aberrant
      assemblies in the presence of taxol.

PMID- 1981944
TI  - Use of DNA amplification for rapid detection of dengue viruses in midgut cells of
      individual mosquitoes.

PMID- 1981945
TI  - Proceedings of the Xth meeting of the World Society for Stereotactic a nd
      Functional Neurosurgery. Maebashi, Japan, October 1989.

PMID- 1981946
TI  - Neural transplantation in mouse Parkinson's disease.
AB  - A complete recovery from the methamphetamine-induced rotational response was
      shown in C57BL/6 (H-2b) mice which had had unilateral 6-OHDA lesions in the
      nigrostriatal pathway about 60 days after transplantation of approximately 1 x
      10(6) dopamine-rich cells from syngeneic or allogeneic (C3H/HeN, H-2k) mouse
      embryos (ED 15), without immunosuppressive agents. Morphological examination
      showed tyrosine-hydroxylase-immunoreactive cell clusters around the needle tract
      in the mice which were transplanted not only with syngeneic cells but also with
      allogeneic cells. This might indicate that so-called immunosuppressive agents are
      not necessary for grafted embryonic cells to survive in an allogeneic mouse
      brain.

PMID- 1981947
TI  - Radioiodine treatment in recurrences of subacute thyroiditis.
AB  - The three cases of subacute thyroiditis treated by radioiodine were refractory to
      systemic corticoid therapy (2-3 recurrences in a mean duration of 7.6 mos) and to
      external antiinflammatory radiotherapy (relapses after 2 and 4 mos,
      respectively). No relapse after radioiodine administration has appeared (mean
      follow-up period: 3 yrs) and post-iodine hypothyroidism was mild.

PMID- 1981948
TI  - Acetaminophen toxicity to cultured rat embryos.
AB  - We tested the effects of acetaminophen on cultured rat embryo development. When
      added directly to culture media at 300 microM, a concentration approximately
      twice the human therapeutic blood level, acetaminophen caused abnormalities in
      the cultured embryos. Sera from both rats and monkeys following gavage with
      acetaminophen were also toxic to cultured embryos. The sera toxicities were
      related to acetaminophen concentrations, and the toxicity could be removed by
      serum dialysis. With regard to the metabolism of acetaminophen, glutathione
      levels in the yolk sac decreased in a concentration related fashion with addition
      of the drug. Also, buthionine sulfoximine, an inhibitor of glutathione synthesis,
      appeared to enhance acetaminophen embryo toxicity, and N-acetylcysteine, a
      glutathione precursor, appeared to protect embryos from acetaminophen toxicity.
      These results suggested that acetaminophen embryo toxicity resulted from direct
      exposure of embryos to acetaminophen and not a maternal metabolite.

PMID- 1981949
TI  - 32P-assay of DNA adducts in white blood cells and placentas of pregnant women:
      lack of residential wood combustion-related adducts but presence of tissue
      specific endogenous adducts.
AB  - Residential wood combustion (RWC), which has been increasingly used as a heating
      source, is of health concern because emissions from RWC contain carcinogenic
      polycyclic aromatic hydrocarbons (PAH). To assess health risk, the possible
      formation of PAH-DNA adducts in white blood cells (WBC) and placentas of
      nonsmoking women exposed to RWC smoke during pregnancy was measured by a nuclease
      P1-enhanced 32P-postlabeling assay having a sensitivity limit of one lesion per
      10(9-10) DNA nucleotides. DNA samples isolated from 12 exposed specimens (8 WBC,
      4 placentas) and 13 unexposed control specimens (8 WBC, 5 placentas) were
      hydrolyzed to mononucleotides, which were then 32P-labeled and separated by high
      resolution thin-layer chromatography. Comparison of autoradiograms of exposed DNA
      samples with those of controls failed to show exposure-related adducts. All
      placental DNA maps exhibited one major (47 +/- 10%) and 12 minor extra spots,
      however, that were not seen on WBC-DNA maps. These derivatives corresponded to an
      average of 12 (+/- 6) modifications in 10(9) nucleotides. Similarly, WBC DNA
      showed four spots that were absent in placental DNA and were not quantified
      because of their low levels. Neither placental nor WBC DNA adducts coincided
      chromatographically with the product formed by the reaction of benzo(a)pyrene
      diol epoxide I with N2 of guanine in DNA. Although these results suggest that RWC
      smoke does not elicit detectable levels of aromatic DNA adducts in humans, lack
      of evaluation of RWC exposure levels leaves some uncertainty in this conclusion.
      The results, however, clearly show that placental and WBC DNA contain covalent
      modifications that are unrelated to RWC exposure. These DNA derivatives may be
      caused by ingestion and/or inhalation of, or skin contact with, low levels of
      environmental genotoxicants or may arise from endogenous electrophiles of as yet
      unknown origin.

PMID- 1981950
TI  - Analysis of the syndrome of congenital malformations induced in genetically
      defined mice by acute riboflavin deficiency.
AB  - The role of genetics in the expression of a complex syndrome of teratologically
      induced congenital malformations was examined by the use of three inbred strains
      and 15 related crosses of mice. The syndrome, which included various limb, brain,
      orofacial, gastrointestinal, and miscellaneous malformations, was induced by an
      intense riboflavin deficiency produced by feeding the antagonist galactoflavin
      during midgestation. Analyses of the data showed that, although all three strains
      shared the major and most other features of the syndrome, there occurred in its
      manifestation vast quantitative and qualitative differences among them, in which
      they were resembled by their related crosses such as to constitute strain
      specific malformation patterns. The results can be regarded as typifying an
      animal counterpart of human situations, the three strains representing in toto
      the mouse family, each strain individually exhibiting the variety that occurs
      between siblings in expressing a single syndrome.

PMID- 1981951
TI  - Dangerous properties of petroleum-refining products: carcinogenicity of motor
      fuels (gasoline).
AB  - Gasoline contains large numbers of dangerous and cancer-causing chemicals such as
      benzene, butadiene, toluene, ethylbenzene, xylene, trimethyl pentane,
      methyltertbutylether (MTBE) and many others. For the U.S. alone approximately 140
      billion gallons of gasoline were consumed in 1989. An increase in only ten cents
      per gallon in price of gasoline generates 14 billion dollars in extra profit per
      year for oil industry cartel. Laboratory animals exposed to gasoline developed
      cancers in different tissues and organs. A number of epidemiological studies in
      humans provide evidence of increased cancer risk of leukemia, kidney, liver,
      brain, lymphosarcoma, lymphatic tissue pancreas and other tissues and organs.

PMID- 1981952
TI  - Induction of micronuclei and toxic effects in embryos of pregnant rats treated
      before implantation with anticancer drugs: cyclophosphamide, cis-platinum,
      adriamycin.
AB  - To evaluate a possible relationship of maternal exposure to anticancer drugs
      during the preimplantation period to blastopathies and postimplantation
      embryotoxicity, CD female rats were injected intraperitoneally on day 3 of
      pregnancy with 15 and 30 mg/kg of cyclophosphamide (CPA), 2 and 4 mg/kg of
      Adriamycin (ADR), 3 and 6 mg/kg of cis-platinum (Cis-Pt), or with 5 ml/kg of
      saline. Blastocysts were collected on day 5 of gestation and evaluated for gross
      morphology, cell number, and micronuclei. Some females were sacrificed on day 21
      of pregnancy in order to evaluate postimplantation embryotoxicity. A reduction in
      cell number/blastocyst was observed only in animals exposed to Cis-Pt 6 mg/kg;
      vice versa, a dose-related increase of micronuclei and of blastocysts with
      micronuclei was found in all groups treated with the anticancer agents. A
      significant increase of postimplantation loss was recorded in the groups treated
      with high doses of Cis-Pt and ADR, but no clear signs of teratogenicity were
      observed.

PMID- 1981954
TI  - Selectivity of action can be achieved with compounds acting at second messenger
      targets.

PMID- 1981953
TI  - ADP-ribosylation of cerebrocortical synaptosomal proteins by cholera, pertussis
      and botulinum toxins.
AB  - Certain microbial toxins ADP-ribosylate G proteins that may be related to those
      postulated to participate in secretion, whilst botulinum neurotoxins, produced by
      Clostridium botulinum, block Ca2(+)-dependent neurotransmitter release. Thus,
      botulinum, pertussis and cholera toxins were examined for ADP-ribosyl transferase
      activity using isolated nerve terminals. Although type D botulinum, cholera and
      pertussis toxins exhibited such enzymic activity, this was not detectable with
      types A or B botulinum neurotoxins or their individual chains, in any
      synaptosomal fraction. Botulinum type D and pertussis toxins ADP-ribosylated
      proteins with mol. wt approximately 24,000 and 42,000 respectively, whereas
      cholera toxin modified several proteins including a 51,000/47,000 mol. wt
      doublet. Pre-incubation of synaptosomes with type A, B or D toxins did not
      inhibit type D-induced labelling in the corresponding lysate. Similar pre
      incubations with cholera or pertussis toxins reduced ADP-ribosylation of their
      substrates. Hence, under conditions in which these botulinum toxins were shown to
      block Ca2(+)-dependent transmitter release no ADP-ribosylated substrate was
      produced in the intact nerve terminals. Moreover, direct correlation was not
      found between the concentration dependencies of type D toxin for protein
      modification and inhibition of [3H]noradrenaline release from synaptosomes. These
      collective findings implicate C3, a non-neurotoxic contaminant of type D, in the
      enzymic action. The substrate for type D toxin was found in the cytosolic
      fraction and to a lesser extent in synaptic membranes, the reverse of the
      situation for pertussis toxin. A combination of the membranes and cytosol was
      required for maximal labelling of the 51,000/47,000 doublet by cholera toxin.
      Purified synaptic vesicles contained proteins labelled by type D and pertussis
      toxins but lacked major cholera toxin substrates. Future research will determine
      the possible involvement of these toxin-susceptible vesicular proteins in
      transmitter release.

PMID- 1981955
TI  - [Rehabilitation of patients with short amputation stumps of the feet after blast
      injuries].
AB  - The author has performed 18 operations for correction of short amputation stumps
      after burst injury. Effective results were obtained in 12 patients. In patients
      with abruption of the anterior part of the foot operations after A. V. Rozhkov
      and V. A. Kudryavtsev are recommended.

PMID- 1981956
TI  - [The treatment of hypertension patients with neurological disorders].
AB  - The authors describe the efficiency of complex treatment of patients suffering of
      hypertensive disease with phenomena of dyscirculatory encephalopathy. It is
      concluded that cavinton and pyracetam depending on the type of central
      hemodynamics and type of vegetative nervous activity proved effective.

PMID- 1981957
TI  - [The APUD system and the prospects for using neuropeptides in the clinic (a
      review of the literature)].

PMID- 1981958
TI  - [Pharmachem's salazopyrine in rheumatoid arthritis].
AB  - 35 patients with classical form of rheumatoid arthritis were treated with
      Salazopyrin N "Pharmachim" prepared with the basic substance of the firm "AB
      Uppsala"--Sweden. Side effects were seen in 9 patients and in 3 of them the
      treatment had to be discontinued. After a six months course of treatment
      remission was found in 18 patients (51%), in 8 patients (22.8%) the result was
      considered "good" with reduction of the inflammatory activity and in the
      remaining 5 patients there was little or no effect. The results coincide with
      those of other authors and support the data for the beneficial action of
      Salazopyrin N as a basic means in the treatment of rheumatoid arthritis. They
      also prove that the Bulgarian drug Salazopyrin N is of good quality and can be
      successfully used in the treatment of rheumatoid arthritis.

PMID- 1981959
TI  - Immunochemical and ultrastructural studies of an ovarian strumal carcinoid.
AB  - An ovarian strumal carcinoid which synthesized peptide hormones, but did not
      induce the carcinoid syndrome, was analysed histochemically,
      immunohistochemically and ultrastructurally. Dot-immunobinding assays were
      performed in order to determine the endocrine gene expression. The amylase
      resistant colloid was found to be PAS-positive in the follicular portions of the
      tumour. Carcinoid cells showed Grimelius positive argyophilic granules in the
      subnuclear position. The Fontana-Masson argentaffin reaction was negative.
      Immunohistochemistry for adrenocorticotropic hormone (ACTH) revealed strong
      reactivity in the follicular areas of the carcinoid. The immunoreactivity for
      somatotropic release inhibiting factor (SRIF) was found positive in the
      trabecular portion of the carcinoid tumour, thyroglobulin in the follicles.
      Neuron-specific enolase, protein S-100 A/B, synaptophysin and chromogranin A
      evoked weak cytoplasmic immunostaining of the tumor cells. Dot-immunobinding
      assays substantiated these immunohistochemical results, except for the
      thermolabile protein S-100 A/B. Electron microscopy of tumor cells showed
      numerous electron-dense cytoplasmic granules, 250 to 350 nm in diameter, both in
      follicular and trabecular areas of the tumor. Plasma levels of tumor-associated
      ACTH, SRIF and thyroglobulin were measured by radioimmunoassay and were found to
      be within the normal range.

PMID- 1981961
TI  - Proceedings of the workshop on Application of Cybernetics in Clinical
      Neurophysiology. Naples, February 15th, 1990.

PMID- 1981960
TI  - [Brain mechanisms of perception of realized and non-realized stimulus. Vitebsk,
      May 10-17, 1989].

PMID- 1981962
TI  - Adenyl cyclase activity in human alveolar macrophages.
AB  - The inflammatory mediators PGE2, DC-PGI2 and histamine as well as the beta
      adrenergic drugs isoprenaline and salbutamol increase intracellular cyclic AMP
      concentrations whereas Platelet Activating Factor does not induce any change in
      adenyl cyclase activity of normal human alveolar macrophages. Functional H2
      histaminergic and beta 2-adrenergic receptor-subtypes are coupled to macrophage
      adenyl cyclase.

PMID- 1981963
TI  - Amino acids as modulators of cholinergic nerves in airways.
AB  - The bronchial smooth muscle of rat was examined for contractile responses to
      excitatory amino acids. The electrical field stimulation (EFS) which induces
      release of ACh, induced contraction which was enhanced by exogenous L-glutamate
      (L-glu). The ED50 of L-glu was 3.5 +/- 0.1 mM. Inhibition of the release by TTX
      or by HC-3 completely abolished the potentiation of the EFS-induced contraction
      by L-glu. The effect of L-glu is therefore probably a prejunctional effect.
      Concentrations of L-glu higher than 22 mM inhibited the EFS evoked contractions,
      and enhanced the tonus of the muscle by a postjunctional stimulation. The ED50 of
      ACh was not altered by L-glu. In contrast, an increase of the intrinsic activity
      (alpha) of ACh was seen, providing evidence for a postjunctional potentiation of
      ACh induced contraction. L-glu did not inhibit AChE-activity at concentrations up
      to 50 mM, indicating that the effect is not due to an accumulation of ACh. A
      relaxation of the EFS-induced bronchial smooth muscle contraction was seen with
      high concentrations of D-glu, L-asp, L-alpha-amino adipate and ibotenate. Neither
      L-GDEE nor DL-APV had any inhibitory effect on L-glu and L-asp induced alteration
      of EFS-evoked contraction or on the L-glu enhanced tonus of the bronchial smooth
      muscle. Kainate, NMDA and quisqualate had only minor transient potentiating
      effects on the EFS-induced contraction.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1981964
TI  - International seminar on pharmacokinetics of veterinary drugs. 11-12 October
      1989, Fougeres, France. Proceedings.

PMID- 1981965
TI  - The prognostic value of thyrotropin receptor antibody (TRAb) levels in Graves'
      disease.

PMID- 1981966
TI  - Research in health sciences, an indispensable tool for development. 14-15
      December 1989, Antwerp, Belgium.

PMID- 1981967
TI  - Pattern formation in plants and animals.

PMID- 1981968
TI  - Potential histamine H2-receptor antagonists. Synthesis, conformational studies
      and activity of novel 3-oxo-1,2,5-thiadiazole 1,1-dioxide derivatives.
AB  - New histamine H2-receptor antagonists bearing a novel "urea equivalent", the 3
      oxo-1,2,5-thiadiazole 1,1-dioxide ring, have been synthesized in a transamination
      reaction. Open chain derivatives have also been obtained. Theoretical
      conformational analysis of the compounds has been carried out using a molecular
      modelling program. Semiempirical CNDO/2 calculations have also been performed.
      The antisecretory and cytoprotective activities of the compounds have been
      evaluated.

PMID- 1981969
TI  - Antianaphylactic and antihistaminic activity of the non-steroidal anti
      inflammatory compound nimesulide in guinea-pig.
AB  - Nimesulide (4-nitro-2-phenoxymethane sulfonanilide, Aulin, Mesulid) is a non
      steroidal anti-inflammatory compound which shows antihistaminic activity and
      inhibits the immune release of histamine. The antihistaminic activity of this
      compound is specific for H1-receptor and has been demonstrated on isolated strips
      of guinea-pig trachea and on histamine-induced multiphasic inotropic response in
      left atria of guinea pig electrically driven. The effect of nimesulide is of non
      competitive type and, at the concentration of 1 x 10(-5) mol/l, is nearly 2 time
      less potent than pyrilamine (mepyramine) at 1 x 10(-6) mol/l. Nimesulide (1.6
      mumol/kg i.v.) inhibits both bronchoconstriction (69%) and TXB2 formation (93%)
      induced by histamine (0.05 mumol/kg i.v.) in anaesthetized guinea-pigs. In
      contrast indomethacin (1.6 mumol/kg i.v.) decreases the generation of TXB2 (89%)
      without affecting the enhancement in tracheal insufflation pressure induced by
      histamine. In actively sensitized guinea-pigs both nimesulide and indomethacin
      protect the animals from deadly anaphylactic crisis. The rise in tracheal
      pressure induced by the antigenic challenge is inhibited of 80% and 63%
      respectively by nimesulide and indomethacin (6.4 mumol/kg i.v.). At this dose the
      two compounds reduced of 90% approximately the immunological release of TXB2 in
      the circulation. The release of histamine, induced by the anaphylactic reaction
      caused in perfused lungs obtained from actively sensitized guinea-pigs, is
      lessened by nimesulide (EC50 = 3.06; fid. lim. 2.59-3.63 mumol/l) and potentiated
      by indomethacin (EC50 = 0.89; fid. lim. 0.67-1.17 mumol/l).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1981970
TI  - International Symposium. Health-related water microbiology. International
      Association on Water Pollution Research and Control Specialist Group on Health
      Related Water Microbiology. 1-6 April 1990, Federal Republic of Germany.
      Abstracts.

PMID- 1981971
TI  - Synthesis and activity of 1,4-dihydropyridine analogues of histamine H2-receptor
      antagonists.
AB  - Compounds of the type Het-CH2-S-CH2-CH2-Y were prepared, in which Het was 2-, 3-
      or 4-pyridyl, and Y was a derivative of 2-cyano-1,1-iminodiamine or 2-nitro-1,1
      ethenediamine in which the terminal nitrogen was incorporated into a 1,4
      dihydropyridine ring (general structure 7; X = NCN or CHNO2). Pharmacological
      testing using the histamine-induced guinea pig atrial chronotropic response
      indicated that the pyridyl substituent position was a determinant of activity,
      the activity order within each isomeric series being usually 2-pyridyl greater
      than 3- and 4-pyridyl. There was no significant difference in activity between
      otherwise similar compounds derived from 2-cyano-1,1-iminodiamine (7, X = NCN) or
      2-nitro-1,1-ethenediamine (7, X = CHNO2). All compounds had a substituent (R)
      attached to the C-4 position of the dihydropyridine ring, and the nature of the R
      substituent influenced the H2-antagonist activity, the relative activity order
      being usually n-Bu greater than Ph greater than Me. In general, the incorporation
      of the terminal nitrogen into a 1,4-dihydropyridyl ring system favoured
      biological activity, 1-(2-[(4-Pyridylmethylthio)ethylamino])-1-(1-[3-(4, 4
      dimethyloxazolin-2-yl)-4-n-butyl-1,4-dihydropyridyl)-2- cyanoimine (7f) was the
      most potent H2-receptor antagonist exhibiting an activity approaching that of
      cimetidine.

PMID- 1981972
TI  - The discovery of the first beta-adrenergic blocking agents.

PMID- 1981973
TI  - Synthesis of 3-dialkylaminochromans via thallium(III)-induced cyclization of
      allyl aryl ethers.
AB  - The sulfur-containing 3-alkylaminochromans, 5-methoxy-3-[N-(2- methylthioethyl)
      propylamino]chroman (15), 5-hydroxy-3-[N-(2-methylthioethyl)propylamino]chroman
      (5) and 5-methoxy-8-methylthio-3-(dipropylamino)chroman (6), have been prepared
      from 8-bromo-5-methoxy-3-chromanol (11). This precursor was synthesized from 3
      allyloxy-4-bromoanisole (8), by a thallium(III)-mediated ring-closure reaction.
      Compound 11 also served as starting material for the synthesis of 8-bromo-3
      (dipropylamino)-5-methoxychroman (7).

PMID- 1981974
TI  - Inosine monophosphate dehydrogenase inhibitors. Probes for investigations of the
      functions of guanine nucleotide binding proteins in intact cells.
AB  - Taken together, the above reports indicate that the IMP dehydrogenase inhibitors
      are valuable probes for investigation of the biological functions of guanine
      nucleotides in intact cells. While these agents have minor effects on levels of
      other nucleotides and enzymes, non-specific effects can be monitored by addition
      of guanine or guanosine to provide substrates for the salvage pathway of guanine
      nucleotide synthesis. The most important question yet to be resolved in employing
      these agents is why incomplete depletion of intracellular guanine nucleotides
      results in such dramatic effects on G-protein function. Since the level of GTP in
      resting cells is approximately 0.5 mM, even a 90% reduction in GTP levels should
      leave enough nucleotide to adequately activate most known G-proteins, as the
      latter display high binding affinities for guanine nucleotides in cell free
      systems. Several explanations have been proposed to account for this disparity.
      Much of the intracellular guanine nucleotide may be bound or compartmentalized
      and therefore unable to interact with certain G-proteins. Possibly, G-proteins in
      the intracellular environment possess a much lower affinity for GTP that they do
      in cell free system. It may be to the cells' advantage that relatively minor
      fluctuations in levels of GTP result in pronounced alterations in the biological
      function of G-proteins as this effect may provide a physiologically important
      mechanism for the regulation of G-proteins in vivo. Further studies are necessary
      to clarify the mechanisms involved in the regulation of the biological function
      of G-proteins and oncogene products by guanine nucleotides in intact cells.

PMID- 1981975
TI  - Effects of a new bifunctional psoralen, 4,4',5'-trimethylazapsoralen and
      ultraviolet-A radiation on murine dendritic epidermal cells.
AB  - Although some psoralens are therapeutically active in the treatment of cutaneous
      hyperproliferative diseases when combined with UVA (320-400 nm) radiation, the
      toxic effects of these compounds have led physicians to seek new
      photochemotherapeutic agents. One such agent is 4,4',5'-trimethylazapsoralen
      (TMAP), a new bifunctional psoralen compound. We investigated the effects of
      repetitive treatments with TMAP plus UVA radiation on the number of dendritic
      immune cells in murine epidermis and on the induction of phototoxicity. Mice
      treated 3 times per week for 4 weeks with 129 microgram TMAP plus 10 kJ/m2 UVA
      radiation exhibited no gross or microscopic evidence of phototoxicity. During
      this treatment, the numbers of ATPase+, Ia+, and Thy-l+ dendritic epidermal cells
      were greatly reduced, and by the end of the treatment period, few dendritic
      immune cells could be detected. We conclude that morphological alterations of
      cutaneous immune cells can occur in the absence of overt phototoxicity, and that
      TMAP plus low-dose UVA radiation decreases the numbers of detectable Langerhans
      cells and Thy-1+ cells in murine skin.

PMID- 1981976
TI  - Survey of pediatrician's attitudes towards pediatric dental health.

PMID- 1981977
TI  - Effects of dilevalol in the anesthetized pig with a partially occluded coronary
      artery.
AB  - The beta-adrenoceptor antagonist dilevalol in a total dose of 430 micrograms/kg
      i.v., potently suppressed isoprenaline-induced increases in heart rate and max
      LVdP/dt (dose ratios of 42 +/- 6 and 38 +/- 5, respectively, in anesthetized
      pigs), but a dose of 1430 micrograms/kg did not appreciably modify phenylephrine
      induced increases in arterial blood pressure (dose ratio less than 4) in both
      anesthetized and conscious pigs. The actions of dilevalol on ischemic myocardium
      of anesthetized pigs were investigated following a reduction of left anterior
      descending artery flow by 85-90%. Dilevalol (300 micrograms/kg), administered
      after 15 minutes of ischemia, did not affect the ischemia-induced changes in
      systemic hemodynamics (such as heart rate, max LVdP/dt and cardiac output),
      myocardial perfusion, and wall-thickening of the ischemic segment during the
      following 15 minutes of ischemia and 2 hours of reperfusion. The reasons for the
      lack of antiischemic actions are most likely the absence of negative chronotropy
      and an absence of afterload reduction by dilevalol.

PMID- 1981978
TI  - Molecular and cellular mechanisms of action of drugs used to modulate the immune
      response.

PMID- 1981980
TI  - [The Cancerology Forum in 1990].

PMID- 1981979
TI  - Action of drugs in the denervated heart.

PMID- 1981981
TI  - [Roferon: present and future indications].

PMID- 1981982
TI  - Respiratory infections in children. World Conference on Lung Health, 20-24 May
      1990, Boston.

PMID- 1981983
TI  - [Comparison of beta-blocking agents pharmacokinetics in obese and non-obese
      subjects].
AB  - We compared in obese patients and normal subjects, the pharmacokinetics of three
      drugs with different solubility: d,l-sotalol markedly hydrophilic, d,l
      propranolol highly lipophilic, d,l-bisoprolol moderately lipophilic. In obese
      subjects the pharmacokinetic data calculated for sotalol (total clearance (CL),
      volume of distribution (V beta), half-life of elimination (t1/2), were comparable
      with those measured in the controls. Data on bisoprolol showed that total V beta
      increased with excess of body weight, but V beta/kg of body weight was lower in
      obese subjects than in the controls, CL tended to increase and t1/2 was similar.
      As concerned propranolol, total V beta and V beta/kg were significantly lower in
      obese than in control subjects. Cl was decreased in obese patients and t1/2 was
      similar for both groups. It appears that in the obese the diffusion of
      liposoluble beta-blockers in the fatty excess weight remains limited. It is
      possible that a vasoconstrictive effect induced by beta-blockers in adipose
      tissues could restrict their tissular distribution.

PMID- 1981984
TI  - The rapid molecular genetic diagnosis of cystic fibrosis by polymerase chain
      reaction: an experience report.
AB  - The authors report their experience with about two thousand DNA amplifications by
      polymerase chain reaction (PCR) in prenatal diagnosis of cystic fibrosis. The
      method is demonstrated on examples of diagnostic informativity and prenatal
      diagnosis examination in a family at 1 in 4 risk of the disease using closely CF
      linked diagnostic polymorphisms: J3.11/MspI, MetH/MspI, CS7/HhaI, KM19/PstI, Mp6
      d9/MspI and XV2c/TaqI, PCR methodology and safety precautions are discussed.

PMID- 1981985
TI  - Clinical and molecular problems of polycystic kidney disease.
AB  - Using nephrological, genealogical and molecular genetic methods, the authors
      examined 85 members of 19 families with autosomal dominant polycystic kidney
      disease. With the aid of probe 3'HVR, alpha-globin and restriction endonuclease
      Pvu II, the families were found 95% informative. The rate of diagnostic
      reliability was also 95%. The authors verified the homogeneity of the disease in
      the Czech population and the applicability of the probe and endonuclease for
      molecular gene diagnostics in the population.

PMID- 1981986
TI  - NSAIDs--reducing the risk. Proceedings of a symposium. Rio de Janeiro, 19
      September, 1989.

PMID- 1981987
TI  - [The analgesic action of narcotic analgesics and clopheline after the ionizing
      irradiation of rats].
AB  - The ionizing radiation (150 Gy) extended the rat tail flick latency, decreased
      the pain-relief effects of morphine and opioids and enhanced the analgesic effect
      of clopheline. The radiation was followed by a decrease of vocalization threshold
      with a reduction of morphine- and clopheline-induced analgesia. Naloxone (0.1
      mg/kg) eliminated the postradiation analgesia and did not change the hyperalgesic
      effect of the radiation.

PMID- 1981988
TI  - [The effect of catecholaminergic agents on the efficacy of immunostimulants].
AB  - The influence of combinations of immunostimulants (prodigiosin, methyluracil,
      levamisole) and catecholaminergic agents (dopamine, haloperidol, noradrenaline,
      phentolamine, isoproterenol, propranolol) on the results of antibiotic therapy of
      acute generalized Proteus infection and primary immune response to ram
      erythrocytes was studied on outbred albino mice. It was established that the
      agents influencing dopaminergic, alpha- and beta-adrenergic receptors can in some
      cases change the efficiency of the studied immunostimulants. The direction and
      degree of their action depend on the administration schedule.

PMID- 1981989
TI  - [The pharmacokinetic and immunopharmacological aspects of prodigiozan interaction
      with psychotropic agents].
AB  - In experiments on white male mice it was found that an immunostimulant
      prodigiozan suppresses the activity of cytochrome P-450-dependent liver
      monohygenases that results in modulation of the activity of neuroleptics
      (aminazine and haloperidol) administered against its background. Their activity
      is assessed by the "open field "test" and the "tail suspension test". One could
      observe a delay of the occurrence of the neuroleptics' effect and prolongation of
      the effect. Acute toxicity of aminazine was shown to decrease. The changes are
      most probably due to a slowing of metabolism of the neuroleptics in the liver. On
      the other hand, administration of neuroleptics against the background of
      prodigiozan fails to affect its immunostimulating effect despite diverse
      influences of the drugs on the activity of the liver monooxygenase.

PMID- 1981990
TI  - Influence of postnatal maternal stress on blood pressure and heart rate of
      juvenile and adult rat offspring.
AB  - Autonomic control of blood pressure (BP) and heart rate (HR) was tested in
      offspring of rat dams that were unmanipulated (controls) or exposed repeatedly to
      either (1) Postnatal restraint, (2) Postnatal s.c. injections of alkaline saline,
      or (3) Prenatal s.c. alkaline saline. Under urethane anesthesia, BP was higher
      than control in 20-day-old offspring of restrained dams and lower at 80 days. The
      magnitude of the BP response to autonomic ganglionic blockade (chlorisondamine)
      changed in parallel; the control HR accelerator response was reversed at 20 days
      and enhanced at 80 days. Postnatal maternal injections increased BP in 20-day-old
      offspring and lowered it at 80 days. The BP response to blockade was unchanged;
      HR acceleration was attenuated at 20 days and increased at 80 days. No influence
      of Prenatal maternal injections was seen in adult offspring. CONCLUSION: Post-
      not prenatal maternal stress disrupts BP and HR control in rat offspring;
      disruption is greater after restraint than injection. There is sympathetic
      hyperactivity in preweanlings and hypoactivity in adults.

PMID- 1981991
TI  - A detailed multipoint gene map of chromosome 1q.
AB  - Utilizing genotyping data for 23 markers, we have constructed a 21-locus
      multipoint genetic map of the long arm of chromosome 1. Five new RFLPs are
      reported. The map integrates anonymous loci from previous primary linkage maps
      and incorporates markers for 10 coding sequences. These markers form a continuous
      linkage group of 85 cM in males and 141 cM in females. The map was constructed
      employing the LINKAGE and CRIMAP computational methodologies via a stepwise
      algorithm.

PMID- 1981992
TI  - Molecular cloning of the t complex responder genetic locus.
AB  - Although mouse t haplotypes carry recessive mutations causing male sterility and
      embryonic lethality, they persist in wild mouse populations via male transmission
      ratio distortion (TRD). Genetic evidence suggests that at least five t-haplotype
      encoded loci combine to cause TRD. One of these loci, called the t complex
      responder (Tcr), is absolutely required for any deviation from Mendelian
      segregation to occur. A candidate for the Tcr gene has previously been
      identified. Evidence that this gene represents Tcr is its localization to the
      appropriate genomic subregion and testis-specific expression pattern. Here, we
      report the molecular cloning of the region between recombinant chromosome
      breakpoints defining the Tcr locus. These results circumscribe Tcr to a 150- to
      220-kb region of DNA, including the 22-kb candidate responder gene. This gene and
      two other homologs were created by large genomic duplications, each involving
      segments of DNA 10-fold larger than the individual genes.

PMID- 1981993
TI  - Sex, strain, and species differences affect recombination across an
      evolutionarily conserved segment of mouse chromosome 16.
AB  - A region of substantial genetic homology exists between human chromosome 21
      (HSA21) and mouse chromosome 16 (MMU16). Analysis of 520 backcross animals has
      been used to establish gene order in the homologous segment. D21S16h and Mx are
      shown to represent the known proximal and distal limits of homology between the
      chromosomes, while Gap43, whose human homolog is on HSA3, is the next proximal
      marker on MMU16 that has been mapped in the human genome. Recombination
      frequencies (RFs) in four intervals defined by five loci in the HSA21-homologous
      region of MMU16 were analyzed in up to 895 progeny of eight different
      backcrosses. Two of the eight crosses were made with F1 males and six with F1
      females. The average RF of 0.249 in 265 backcross progeny of F1 males was
      significantly higher than the 0.106 average recombination in 320 progeny of F1
      females in the interval from D21S16h to Ets-2. This is in contrast to HSA21,
      which shows higher RFs in female meiosis in the corresponding region.
      Considerable variation in RF was observed between crosses involving different
      strains, both in absolute and in relative sizes of the intervals measured. The
      highest RFs occurred in a cross between the laboratory strain C57BL/6 and
      MOLD/Rk, an inbred strain derived from Mus musculus molossinus. RFs on this cross
      were nearly fivefold higher than those reported previously for an interspecific
      cross between C57BL/6 and Mus spretus.

PMID- 1981994
TI  - Serum amyloid A and P protein genes in familial Mediterranean fever.
AB  - Two recent studies have suggested the involvement of serum amyloid A (SAA) and P
      (APCS) genes in familial Mediterranean fever (MEF). To test the role of SAA and
      APCS in MEF and MEF-amyloidosis, we studied 17 informative families (15
      Armenians, 2 non-Ashkenazi Jews) and 8 MEF patients with amyloidosis using a
      candidate gene approach. No evidence for any MEF-associated polymorphism was
      found in any of the 41 Armenian and Jewish MEF patients tested. Our family
      studies allowed us to rule out tight linkage between SAA and MEF (lod score = 
      2.16, theta less than or equal to 0.06). For APCS we found that the allele
      frequency in the MEF-amyloidosis patients was similar to that in 18 unrelated MEF
      patients without amyloidosis and their 33 healthy parents. Finally, we excluded
      close genetic linkage between APCS and MEF at 8.5 cM or less (lod score = -2.2).

PMID- 1981995
TI  - Mapping of class alpha glutathione S-transferase 2 (GST-2) genes to the vicinity
      of the d locus on mouse chromosome 9.
AB  - Recombinant inbred strains of mice were used to localize the genes coding for the
      class alpha glutathione S-transferase 2 (Gst-2). The genes showed three distinct
      strain distribution patterns, indicating that they occur in at least three
      clusters separable by recombination. All three clusters are located in the
      vicinity of the d locus on mouse chromosome 9, but two of them are closer to d
      than the third. Linked to Gst-2 on mouse chromosome 9 are two enzyme-encoding
      loci, Pgm-3 and Mod-1. The human counterparts of Gst-2, Pgm-3, and Mod-1 map to
      6p12, 6q12, and 6q12, respectively. Thus, the pericentric region of human
      chromosome 6 has its homolog in the segment spanning Gst-2, Pgm-3, and Mod-1 on
      mouse chromosome 9. The fact that the syntenic group extends across the
      centromere of human chromosome 6 can best be explained by a pericentric inversion
      postulated to have taken place in the primate lineage leading to Catarhini.

PMID- 1981996
TI  - [Oxatomide in the treatment of pruriginous skin diseases of various nature].
AB  - A study in two parts was carried out with the aim of developing a formulation of
      oxatomide for topical dermatological use. During the first part of the study the
      safety of 4 formulations (cream and gel at 2.5% and 5%) was evaluated by means of
      the patch-test, while in the second a clinical trial was carried out in order to
      assess the anti-itching efficacy of the formulation chosen on the basis of the
      results of the first part (gel 5%). During the double blind study of safety, only
      one patient out of 33 studied showed a reaction, and with all formulations. In
      the second part of the study 30 patients (16 F, 14 M) were admitted, aged between
      13 and 77 years (mean age 48.2) and suffering from cutaneous diseases with
      itching. The study was open and each subject applied oxatomide gel at 5% twice a
      day for 14 days. There was a subsequent follow-up without therapy of 14 days.
      During the study a significant (p less than 0.01 between times) improvement in
      lesions was observed, with an average reduction of 61% for itching, 54% for
      erythema, 60% for excoriations and 59% for lichenification. Acceptability and
      safety were good. Only one subject suspended treatment due to the onset of
      burning on the site of application. In the follow-up period the therapeutic
      results achieved were generally maintained.

PMID- 1981997
TI  - Cutaneous tuberculosis: atypical skin lesions in immunodepressed patients.
AB  - We report a case of secondary skin tuberculosis due to endogenous secondary
      infection in a 27-year-old subject affected by ulcerative colitis. The clinical
      appearance the lesion was atypical and its classification uncertain. The
      morphology of the lesion and the fact that the primary tubercular complex, at
      pulmonary level, was masked by a simultaneous candidiasis infection were probably
      due to cell-mediated immunodeficiency consequent to the ulcerative colitis and on
      going therapy (Salazopyrin and prednisone). Rapid remission of cutaneous and
      pulmonary lesions was achieved following specific therapy (rifampicin, isoniazid,
      ethambutol).

PMID- 1981998
TI  - Serotonin-, somatostatin- and chromogranin A-containing cells of the urethro
      prostatic complex in the sheep. An immunocytochemical and immunofluorescent
      study.
AB  - The urethral and prostatic epithelial of the sheep contain a large number of
      amine- and/or peptide-producing neuroendocrine cells (NE), also called
      paraneurons. Four different cell types have been immunohistochemically recognised
      among them. The first contains the amine serotonin, the second the protein
      chromogranin A, the third the amine and the protein together and the fourth the
      hormone somatostatin. Serotonin-producing cells are elongated in shape and often
      show cytoplasmic dendrite-like processes directed towards the basal membrane
      and/or the lumen. Chromogranin A-containing cells are polymorphic and constitute
      the more numerous NE subpopulation. Cells containing both the bioactive
      substances seem to be less numerous than the chromogranin A cells and slightly
      more frequent than the serotonin cells. All these cell types are diffused along
      the whole urethro-prostatic complex and show their highest density in the
      collicular zone. Somatostatin-containing cells often show a unique cytoplasmic
      extension directed towards the basal membrane and are rare. It is supposed that
      the presence of serotonin in the urogenital tract is functionally correlated with
      the emission of urine and/or semen, while somatostatin is associated with the
      inhibition of local exocrine and/or endocrine secretions.

PMID- 1981999
TI  - A survey of endocrine cells in the pancreas of the echidna (Tachyglossus
      aculeatus) with special reference to pancreatic motilin cells.
AB  - Pancreatic endocrine cells were examined in a primitive egg-laying mammal, the
      echidna, using immunohistochemistry. Immunoreactive endocrine cells were observed
      using antisera to insulin, glucagon, somatostatin, avian pancreatic polypeptide
      and bovine pancreatic polypeptide. In addition, motilin-immunoreactive cells were
      identified in both the endocrine and exocrine pancreas of pouch-young and adult
      echidnas using three types of motilin antisera. Since the motilin-immunoreactive
      cells did not cross-react with any other pancreatic hormones tested, they are
      identified as an independent endocrine cell type.

PMID- 1982001
TI  - Proceedings of the XII Congress, International Society of Biomechanics. Los
      Angeles, California, 26-30 June 1989.

PMID- 1982000
TI  - Human neutrophil elastase: degradation of basement membrane components and
      immunolocalization in the tissue.
AB  - Human neutrophil elastase was purified to homogeneity as two isozymes named E1
      and E2. The isozymes degraded Type IV collagen, laminin, fibronectin, and heparan
      sulfate proteoglycan similarly to each other. The degradation of such basement
      membrane components by elastase may assist the extravasation of neutrophils in
      the process of inflammation. Among the substrates tested, only type V collagen,
      which is susceptible to neutrophil gelatinase, was resistant to elastase. This
      broad substrate specificity of the enzyme may also contribute to tissue
      destruction at the sites of inflammation. We produced a monoclonal antibody
      against the purified enzyme and applied it to immunohistochemical studies. In
      bronchopneumonia and polyarteritis nodosa, elastase was associated with the
      cleaved elastic fibers, indicating that the enzyme really destroys tissue in
      vivo. In the exudates of rheumatoid joint, elastase was stained as diffuse fine
      granules. Immunohistochemical studies with the monoclonal antibody will provide a
      complementary way to disclose the mechanism of diseases related to neutrophil
      infiltration.

PMID- 1982002
TI  - Determination of loxtidine in human serum by capillary column gas chromatography
      with nitrogen-phosphorus detection.

PMID- 1982003
TI  - Simple high-performance liquid chromatographic method for the analysis of the non
      depolarizing neuromuscular blocking drugs in clinical anaesthesia.

PMID- 1982004
TI  - Liver abnormality in ovarian hyperstimulation syndrome.
AB  - Ovarian hyperstimulation syndrome (OHSS) is a potentially fatal condition
      associated with the therapeutic induction of ovulation in infertility. Liver
      function abnormality has been previously reported in four patients, one of whom
      had ultrastructural abnormalities on liver biopsy. This paper describes a patient
      presenting with severe OHSS 16 days after ovulation had been induced. Liver
      function abnormality was apparent 11 days later, with a sustained rise in
      alkaline phosphatase and aspartate aminotransferase (AST) which lasted up to 2
      months. A liver biopsy performed during the second month of her protracted
      hospital admission showed marked zonal fatty change (acinar zone 1) and
      associated inflammation, with mitochondrial crystalline inclusions and rough
      endoplasmic reticulum dilatation on electron microscopy. This report discusses
      the clinical features and possible aetiological factors.

PMID- 1982005
TI  - Plasticity of GABA- and glutamate-containing terminals in the mouse thalamic
      ventrobasal complex deprived of vibrissal afferents: an immunogold-electron
      microscopic study.
AB  - GABA and glutamate immunogold staining demonstrated that nerve cells of the
      thalamic ventrobasal complex (VB) of mice were positive exclusively for
      glutamate. None of the neuronal perikarya reacted the GABA antibody. By using
      alternate thin sections of the normal VB, it was also shown that large "specific"
      somatosensory and small corticothalamic terminals, both of which contained
      spherical synaptic vesicles, exhibited only glutamate-like immunoreactivity. A
      third axonal type, containing flat-ovoid synaptic vesicles, stained only for
      GABA. Seventy-five days after coagulation of the vibrissal follicles in newborn
      mice, a characteristic multiplication of GABA positive axon terminals was
      observed. In addition, it was demonstrated that, similarly to modified cortical
      endings (Hamori et al., J. Comp. Neurol. 254:166-183, '86), many GABA positive
      terminals appeared as specific afferent endings, replacing the missing "specific"
      vibrissal afferents. This finding shows a remarkable plasticity of inhibitory
      GABA axons during developmental synaptogenesis and provides further evidence that
      the size, location, and the type of attachment of presynaptic terminals are
      dependent on their postsynaptic target.

PMID- 1982006
TI  - Sources of presumptive glutamatergic/aspartatergic afferents to the magnocellular
      basal forebrain in the rat.
AB  - The distribution of presumptive glutamatergic and/or aspartatergic neurons
      retrogradely labeled following injections of [3H]-D-aspartate into the
      magnocellular basal forebrain of the rat was compared with the distribution of
      neurons labeled by comparable injections of the nonspecific retrograde axonal
      tracer wheat germ agglutinin conjugated to horseradish peroxidase. Cells
      retrogradely labeled by wheat germ agglutinin-horseradish peroxidase were found
      in a wide range of limbic and limbic-related structures in the forebrain and
      brainstem. In the telencephalon, labeled neurons were seen in the orbital, medial
      prefrontal, and agranular insular cortical areas, the amygdaloid complex, and the
      hippocampal formation. Labeled cells were also seen in the olfactory cortex, the
      lateral septum, the ventral striatopallidal region, and the magnocellular basal
      forebrain itself. In the diencephalon, neurons were labeled in the midline
      nuclear complex of the thalamus, the lateral habenular nucleus, and the
      hypothalamus. In the brainstem, labeled cells were found bilaterally in the
      ventral midbrain, the central gray, the reticular formation, the parabrachial
      nuclei, the raphe nuclei, the laterodorsal tegmental nucleus, and the locus
      coeruleus. A significant fraction of the afferents to the magnocellular basal
      forebrain appear to be glutamatergic and/or aspartatergic. Only a few of the
      regions labeled with wheat germ agglutinin-horseradish peroxidase were not also
      labeled with [3H]-D-aspartate in the comparable experiments. Most prominent among
      the non-glutamatergic/aspartatergic projections were those from fields CA1 and
      CA3 of the hippocampus, the hilus of the dentate gyrus, the dorsal subiculum, the
      tuberomammillary nucleus, and the ventral pallidum. In addition, most of the
      lateral hypothalamic and brainstem projections to the magnocellular basal
      forebrain were not significantly labeled with [3H]-D-aspartate. In addition to
      these inputs, a commissural projection from the region of the contralateral
      nucleus of the horizontal limb of the diagonal band was confirmed with both wheat
      germ agglutinin-horseradish peroxidase and the anterograde axonal tracer
      Phaseolus vulgaris leucoagglutinin. This projection did not label with [3H]-D
      aspartate or [3H]-GABA, suggesting that it is not glutamatergic/aspartatergic or
      GABAergic. Furthermore, double labeling experiments with the fluorescent
      retrograde tracer True Blue and antibodies against choline acetyltransferase
      indicate that the projection is not cholinergic.

PMID- 1982007
TI  - Cytotoxic effect of glutamate and its agonists on mouse hippocampal neurons.
AB  - The neurodegenerative action of the excitatory amino acid neurotransmitter
      (glutamate) and its exogenous (N-methyl-D-aspartate, kainate) or endogenous
      (quinolinate) analogues were studied on cultures of dissociated nerve cells from
      the embryonal mouse hippocampus. The exposure of primary cultures for 3-6 h to
      these excitotoxins showed that neurons were vulnerable to both glutamate and all
      tested agonists which induced the swelling and vacuolization of neuronal bodies
      accompanied by degeneration of their dendrites. This process terminated by
      complete cell destruction. The neurotoxic effect of glutamate (1 mM) was not
      suppressed by a competitive NMDA receptor antagonist (D, L-2-amino-5
      phosphonovalerate, 0.3 mM) and was only slightly prevented by gamma-D
      glutamylglycine (3mM). The protective action of the latter was more evident in
      the presence of lower glutamate concentration (0.5 mM). The excitotoxic effect of
      N-methyl-D-aspartate (0.1 mM) or quinolinate (0.5mM) was almost completely
      blocked by both antagonists. In contrast, D, L-2-amino-5-phosphonovalerate failed
      to protect hippocampal neurons from damage induced by kainate while partial
      antagonism of kainate neurotoxicity was observed with gamma-D-glutamylglycine.
      These finding suggest that glutamate neurotoxicity may be derived, mainly, from
      the non-NMDA type(s) of glutamate receptor present on hippocampal cell membranes
      with a low effectiveness to suppress this effect by selective competitive NMDA
      antagonist. Possible involvement of glutamate receptor(s) in the early dendritic
      outgrowth of hippocampal neurons and in the process of neuronal "cell death" is
      discussed.

PMID- 1982008
TI  - [Undescended testes. Current state of knowledge].
AB  - Undescended states are a frequent abnormality, which still has a controversial
      pathogenesis. The gubernaculum testis plays a major part, with a double hormonal
      control by anti-mullerian and androgenic hormones. Undescended testes present
      with acquired histological lesions that start developing during the 2nd year of
      life. Similar lesions can appear in the normally descended contralateral testis.
      Once acquired, these lesions are hardly or not reversible, and often associated
      with abnormalities of the epididymis and of the vas deferens. Infertility and
      cancer of the testis are the major risks of evaluation of this affection. The
      risks of cancer have been reassessed, and are now estimated to be 5 to times as
      high as for healthy men. Surgical descent of the testis does not decrease the
      risks. Cancer of the testis can be prevented by searching for in situ carcinoma
      on surgical biopsies. However, a population at higher risks, in which screening
      would be effective, still has to be defined among the patients with undescended
      testis, as the incidence of in situ carcinoma in a population with a history of
      undescended testis is about 2%. Hormonal treatments with HCG our LH-RH must
      always be used as first-intention treatments as they are innocuous, but they are
      not very effective. The treatment of an undescended testis is therefore mainly
      surgical. The decision must be made during the second year of life, before
      histological lesions of the testes occur.

PMID- 1982009
TI  - Cancer of the exocrine pancreas: new horizons. Proceedings of a symposium. June
      15-17, 1989, Toledo, Ohio.

PMID- 1982010
TI  - HIV-1 variability and progression to AIDS: a longitudinal study.
AB  - HIV-1 replicative activity and its relation to the clinical and immunological
      evolution of infection was studied in a group of 150 HIV-1 seropositive Italian
      i.v. drug abusers over a 1 year period. HIV-1 was isolated from 90 (60%)
      subjects; two groups of isolates were distinguished, according to replicative
      activity "in vitro" and ability to induce cytopathic effects in cell cultures,
      and were termed "rapid-high" and "slow-low" viruses, in agreement with other
      workers. Rapid-high viruses were recovered more frequently from patients with
      ARC/AIDS, while slow-low viruses seemed related to the asymptomatic period of
      infection. The replicative properties of HIV-1 seem to affect strongly the course
      of disease. In fact, an important CD4 cell decline occurred in asymptomatic
      subjects with rapid-high virus infection; asymptomatic subjects with negative
      viral cultures or with slow-low viruses showed no such decline. Asymptomatic
      subjects with negative viral cultures had no signs of disease during the
      observation period, while 9% with slow-low virus and 45% with rapid-high virus
      progressed to AIDS.

PMID- 1982011
TI  - Nutritional losses due to food preparation and possibilities of their prevention.
      XIV International Congress of Nutrition. August 25th., 1989, Seoul, Korea.

PMID- 1982013
TI  - Indirect ambulatory blood pressure monitoring. An international conference. 1-3
      March 1990, Berlin, Germany.

PMID- 1982012
TI  - Aspartyl- and glutamyl-lysine crosslinks formation and their nutritional
      availability.
AB  - Transglutaminase-catalyzed incorporation of L-lysine into wheat gliadin rendered
      the lysine-fortified protein poorly digestible in the in vitro tests. In rat
      feeding tests, however, the luminal leavings and excreta collected after
      administration of the [14C]lysine-fortified gliadin contained less than one-tenth
      of the radioactivity originally administered to rats. The enzymes, gamma
      glutamylamine cyclotransferase and 5-oxoprolinase, known to occur in animal
      kidney are at least in part responsible for the observed high availability of
      isopeptide bound lysine. A novel enzyme which is capable of directly hydrolyzing
      the cross-linked isopeptide into component amino acids and peptides, "N epsilon
      (gamma-glutamyl)lysine hydrolase" was found in the isolated microorganisms which
      can use the synthesized N epsilon-(gamma-glutamyl)lysine as their only source of
      carbon and nitrogen. The enzyme(s) appear to be effectively used for improving
      digestibility and availability of protein matrixes formed in normal metabolism
      and by heat and/or shear treatment commonly used in food processing.

PMID- 1982014
TI  - NMDA antagonists prevent hypothermic injury and death of mammalian spinal
      neurons.
AB  - Prolonged (2-6 h) cooling of monolayer cultures of dissociated murine spinal cord
      at temperatures below 17 degrees C caused pronounced swelling of neuronal
      perikarya and dendrites. The numbers of swollen neurons in a culture increased as
      the temperature was reduced, and at 7 degrees C-10 degrees C all of the neurons
      were swollen. On rewarming the cultures to 37 degrees C, the majority of the
      swollen neurons died (up to 74% at 10 degrees C). Glial cells were not affected.
      Addition of the NMDA antagonists D-2-amino-5-phosphonovalerate (DAPV, 100
      microM), ketamine (100 microM), and dibenzocyclohepteneimine (MK801, 10 microM)
      to spinal cord cultures before lowering the temperature to 10 degrees C minimized
      the dendrosomatic swelling and reduced neuronal mortality from 74% to 10%. These
      data show a surprising sensitivity of some neurons to nonfreezing low
      temperatures and suggest direct involvement of the NMDA receptor in hypothermia
      related neuronal death.

PMID- 1982015
TI  - [Clinical investigation of urinary dipeptidyl aminopeptidase IV (DAP IV) activity
      in patients with primary glomerular diseases].
AB  - To assess the role of urinary dipeptidyl aminopeptidase IV (DAP IV) in glomerular
      diseases, we measured urinary levels of DAP IV in 55 patients with chronic
      glomerulonephritis (CGN), 41 patients with nephrotic syndrome (NS), 21 patients
      with chronic renal failure (CRF) and 48 normal controls. The urinary DAP IV
      levels in patients with CGN were significantly higher than those in normal
      controls and were higher in patients with more active disease. The frequency of
      normal urinary DAP IV levels in patients with CGN was significantly lower than
      that of normal urinary N-acetyl-beta-D-glucosaminidase (NAG) levels in those with
      CGN. The urinary DAP IV levels in patients with NS were the highest among the 3
      patient groups. The urinary DAP IV/g.protein ratio was significantly lower in the
      patients with minimal change nephrotic syndrome than in those with membranous
      glomerulonephritis or membranoproliferative glomerulonephritis. In both patients
      with CGN and those with NS, urinary DAP IV levels correlated significantly with
      the amounts of urinary protein and the urinary NAG levels. The urinary DAP IV
      levels in patients with CRF were lower than those in patients with CGN and NS who
      had normal GFR, and there was a significant negative correlation between the
      urinary DAP IV levels and the serum creatinine levels. We conclude that the
      measurement of urinary DAP IV is useful for detecting or monitoring glomerular
      disease.

PMID- 1982016
TI  - [Human immunodeficiency virus type 2 infection: is it really present in our
      area?].

PMID- 1982017
TI  - Inhibition of angiotensin III formation by thiol derivatives of acidic amino
      acids.
AB  - Angiotensin III is formed by removal of the N-terminal Asp residue of angiotensin
      II in a reaction catalyzed by glutamyl aminopeptidase (aminopeptidase A EC
      3.4.11.7). Thiol derivatives of glutamate and aspartate in which the alpha-COOH
      group was replaced by -CH2SH were synthesized as inhibitors of glutamyl
      aminopeptidase. Glutamate thiol was a potent inhibitor of glutamyl aminopeptidase
      (Ki = 4 x 10(-7) M) but even more potently inhibited microsomal alanyl
      aminopeptidase (Ki = 2.5 x 10(-7) M). Aspartate thiol (beta-homocysteine) was a
      less potent but more selective inhibitor of glutamyl aminopeptidase (glutamyl
      aminopeptidase: Ki = 1.2 x 10(-6) M; microsomal alanyl aminopeptidase: Ki = 7.5 x
      10(-6) M). Neither compound inhibited cytosolic leucyl aminopeptidase. Aspartate
      thiol blocked the conversion of angiotensin II to angiotensin III. These
      derivatives are more selective than amastatin and may be of value in studies
      probing the biological significance of angiotensin III.

PMID- 1982018
TI  - U.N. convention on the rights of children.

PMID- 1982020
TI  - 3rd International MONICA Congress. Nice (France), September 15-16, 1989.

PMID- 1982019
TI  - Ready as ever.

PMID- 1982021
TI  - [Hispanic-Portuguese Congress of Cardiology. 28-31 October 1990, Seville.
      Abstracts].

PMID- 1982022
TI  - Etodolac: the role of a new NSAID in the management of arthritis and pain. Tenth
      Pan American Congress of Rheumatology and the Seventeenth Congress of the Mexican
      Society of Rheumatology. Guadalajara, Mexico, March 15, 1990.

PMID- 1982023
TI  - [Cholecystokinin octapeptide (CCK-8) antagonized analgesia mediated by mu and
      kappa opioid receptors].
AB  - CCK-8 has been shown to antagonize the analgesia produced by morphine or
      endogenous opioid peptides. The present study was performed to clarify the
      interaction between CCK-8 and different opioid ligands. Analgesia produced by
      intrathecal (I.T.) injection of the specific mu receptor agonist PL017 10 ng or
      kappa receptor agonist NDAP 500 ng can be antagonized by I.T. injection CCK-8 at
      a dose as small as 4 ng. In contrast, analgesia produced by I.T. injection of the
      delta receptor agonist DPDPE (6.5, 13 and 26 micrograms) was not blocked by CCK-8
      (4 ng or 40 ng, I.T.). The antagonistic effect of CCK-8 on PL017 and NDAP could
      be completely reversed by proglumide (3 micrograms, I.T.). I.T. injection of CCK
      8 (4 or 40 ng single dose or cumulative dose of 0.1, 0.2, 0.5 and 1.0 microgram
      at 10 min intervals) produced neither analgesia nor hyperalgesia. In conclusion,
      CCK-8 preferentially antagonizes opioid analgesia mediated by mu and kappa
      receptors, and this antagonistic effect is mediated by CCK receptors.

PMID- 1982024
TI  - [Effects of dynorphin A and CCK-8 on synaptosomal 45Ca uptake of the rat spinal
      cord].
AB  - Cholecystokinin octapeptide (CCK-8) and angiotensin I (AI) have been shown in
      behavioral studies being endogenous antiopioid substrates (AOS). To assess their
      antiopioid mechanism at postreceptor level, we observed the effects of the three
      opioids and the two AOS on 45Ca uptake of the rat spinal synaptosomal
      preparations. Morphine, Dyn A and DPDPE at concentrations of 10 nmol/L to 1
      mumol/L, produced a mild suppression of 45Ca uptake of synaptosomal preparations
      from ventral spinal cord. CCK-8 showed a mild suppression only at a concentration
      of 1 mumol/L. In synaptosomes prepared from dorsal spinal cord, Dyn A but not
      morphine or DPDPE, produced a strong inhibition of 45Ca uptake which was blocked
      by nor-BNI, a kappa receptor antagonist, at 1 mumol/L. While CCK-8 (10 nmol/L to
      1 mumol/L) also suppressed 45Ca uptake, it could antagonize the suppressive
      effect induced by Dyn A. In contrast to CCK-8, AI (10 nmol/L to 1 mumol/L)
      influenced neither on synaptosomal 45Ca uptake, nor on Dyn A suppression of 45Ca
      uptake. The results presented above fit very well with our behavioral studies,
      i.e., CCK-8 antagonized opioid analgesia in both the brain and the spinal cord,
      whereas AI antagonized opioid analgesia in the brain but not in the spinal cord.
      It is therefore concluded that antagonism of the opioid suppression of
      synaptosomal 45Ca uptake might be one of the mechanisms for the antiopioid
      activity of CCK-8 and AI.

PMID- 1982026
TI  - The place of dipyridamole in modern cardiology: the benefits of 30 years'
      experience. The proceedings of a symposium at the XIth World Congress of
      Cardiology. 13 February 1990, Manila.

PMID- 1982025
TI  - [Influence of septohippocampal lesion on the levels of some neurotransmitters and
      enzymes in the rat hippocampus].
AB  - Partial deafferentation of the hippocampus was obtained by transection of
      unilateral partial fimbria-fornix. On the seventh postoperational day, there
      appeared in the lesioned hippocampus respectively a 72.5%, 45.7% and 52.2%
      reduction in acetylcholine content, choline acetyltransferase and cholinesterase
      activity. A concomitant 16.3%, 31.1% and 30.3% reduction in noradrenaline,
      dopamine and serotonin content respectively was also observed, while amino acids
      content did not show any change. The results indicate that the cholinergic and
      monoaminergic afferents of the hippocampal formation in the rat reach their
      target regions via the fimbria-fornix.

PMID- 1982027
TI  - Sendai-forum on Clinical Neurology.

PMID- 1982028
TI  - Involuntary movements.
AB  - Movements disorders are prominent symptoms in many neurological diseases,
      especially with affection of the basal nuclei. Several of these diseases have
      characteristic symptoms and signs, whereas clinical diagnosis is more difficult
      in other diseases. The various movement disorders, hypokinesia, hyperkinetic
      syndrome, tremor etc. are defined and described, and clinical features of the
      various diseases were commented on.

PMID- 1982029
TI  - Intractability of complex partial seizure with secondary generalization: kindling
      studies in cats.
AB  - Among many factors linked to an intractability of partial seizure secondarily
      generalized, changes in the brain resulting from repeated epileptic seizures are
      discussed mainly in light of our evidence obtained from kindling studies in cats.
      In addition, the literatures on biological mechanisms of the kindling effect are
      reviewed briefly. The evidence demonstrated and reviewed here indicates that: 1)
      limbic structure is not susceptible to develop generalized convulsions initially,
      2) repeated attacks of limbic seizures result in a profound reduction in seizure
      threshold at the primary epileptogenic focus in the limbic structures, 3) once a
      limbic seizure developed to secondarily generalized convulsion, it seldom changes
      into the original partial seizure, 4) kindled events in the limbic structures are
      more profound and persistent than that in the cerebral cortex, and 5) repetition
      of focal cortical or limbic seizures may eventually produce spontaneous
      convulsive seizures originating in the limbic structures. These findings strongly
      suggest that the limbic system, rather than the cerebral cortex, is more
      susceptible to a lasting functional change resulted from seizure repetition,
      which can lead to an intractability of epilepsy with partial seizure. Lasting
      changes in the cell membrane including long-lasting enhancement of inositol
      phospholipid hydrolysis of the amygdala stimulated by excitatory amino acid
      appear important for development of trans-synaptic changes underlying the
      kindling-induced seizure susceptibility.

PMID- 1982030
TI  - Ammon's horn sclerosis: its pathogenesis and clinical significance.
AB  - Sclerosis of the cornu Ammonis or Ammon's horn sclerosis (AHS) is an "often
      described, yet hitherto enigmatic phenomena" as Spielmyer put it in 1927. It has
      been found in cases with ischemia, anoxia or hypoglycemia and in more than half
      of the epileptic brains examined at autopsy. Various theories about its
      pathogenesis have been propounded. Among them, the "Pathoklise" theory of the
      Vogts and the vascular theory of Spielmeyer and his associates were prevailing
      until recently. In 1953, two articles were published to contribute to the
      pathogenesis of ictal automatism (a type of complex partial or temporal lobe
      seizures). One is the incisural sclerosis theory by Penfield and his associates
      and the other is the Ammon's horn sclerosis theory by Sano and Malamud. The
      former authors described a diffuse sclerosis of the infero-mesial temporal
      structures without, however, specifically relating it to AHS. They considered it
      was the result of localized anoxia of that portion of the brain caused by
      incisural herniation occurring during parturition. Sano and Malamud maintained
      that AHS is a result of convulsions, a distinct scar adjacent to which
      epileptogenic foci may develop in the course of time to cause ictal automatism.
      The latter theory was corroborated by Sano, Falconer and others. Falconer
      expanded the theory to the assertion that not only ictal automatism but other
      types of intractable epilepsy may be due to "mesial temporal (Ammon's horn)
      sclerosis". The most recent development in the pathogenesis of AHS is the
      excitotoxicity theory. Namely, AHS is caused by excessive excitation of neurons,
      probably by putative excitatory neurotransmitters, especially, glutamate. For
      this theory, there is a significant body of evidence. The problem of AHS, an old
      research subject and a matter of long-lasting controversy, has now been updated
      and become one of the newest topics in the field of experimental neurobiology.

PMID- 1982031
TI  - [The characteristics of calcium and phosphorus metabolism in the body under the
      conditions of an altered habitat].

PMID- 1982032
TI  - [The role of Hantaan virus serotypes in the etiology of hemorrhagic fever with
      renal syndrome in the Far East of the USSR].
AB  - The employment of two serological tests (indirect fluorescence antibody technique
      and neutralization test) demonstrated the leading role of Hantaan virus serotype
      1 strains isolated from field mice in the pattern of the incidence of hemorrhagic
      fever with renal syndrome (HFRS). Proofs of the etiological importance of strains
      of serotypes 3 and 5 occurring in brown rats and Cl. rufocanus were obtained. No
      data on any association of human HFRS cases with strains of serotype 4 isolated
      from reed voles could be demonstrated.

PMID- 1982033
TI  - Iscom (immunostimulating complex) vaccines containing mono- or polyvalent pili of
      enterotoxigenic E. coli; immune response of rabbit and swine.
AB  - Iscom (immunostimulating complex) vaccines were prepared to contain K88ab, K88ac,
      K99 and 987P pili (fimbriae) of enterotoxigenic E. coli bacteria as monovalent or
      quadrivalent preparations. The iscoms injected into rabbits and into pigs
      elicited similar or higher immune response in both animal species than the oil
      adjuvanted vaccine containing about 5 times more of the same pilus protein. It is
      concluded that inclusion of pili into iscoms results in immunogenic preparations
      likely worth pursuing for vaccine production against enterotoxic colibacillosis
      of newborn pigs. The iscoms did not induce local reaction at the injection sites
      in contrast to the oil adjuvanted vaccines.

PMID- 1982034
TI  - Metipranolol and tergurid induced enhancement of delayed hypersensitivity and
      sedative effect in stressed calves.

PMID- 1982035
TI  - Comparison of pharmacotherapeutic procedures in the treatment of sexual deviant
      behaviour.

PMID- 1982036
TI  - The paradox effect of psychostimulants in the treatment of the child hyperkinetic
      syndrome.

PMID- 1982037
TI  - HLA class II (DR, DQ) in Japanese patients with type 1 diabetes mellitus.
AB  - DNA restriction fragment length polymorphism (RFLP) typing of HLA-DR and DQ
      alleles of 60 Japanese type 1 (insulin dependent) diabetic patients and 115
      controls was performed. RFLP typing of DRB1 showed increased frequency of DR9 and
      decreased frequencies of DR2 and DRW6 among patients compared to controls. In the
      RFLP typing of BamHI-digested DNA to DQ beta probe (BamHI-DQB1), the incidence of
      the 10.26 kb fragment, which represents either DQW4, DQW8 or DQW9, was markedly
      elevated in the patients, whereas the incidence of DQW6 was reduced. The
      predicted DR-DQ haplotype study revealed that DR4-DQW4 or DQW8, DRW8-DQW4 or DQW8
      and DR9-DQW9 may contribute to susceptibility to type 1 diabetes. When
      serological typing of the 13 DRW8 patients was performed, all the 11 DRW8
      patients carrying DQW4 or DQW8 (BamHI-10.26 kb) were positive for DQW3. These
      results indicated that the HLA-DQ locus may play an important role in the
      development of type 1 diabetes in the Japanese as well as other ethnic groups and
      that the DRW8-DQW8 haplotype may predispose to the disease in Japan.

PMID- 1982038
TI  - [Study on metabolism of phenmetrazine-like drugs and their metabolites].
AB  - We have studied the metabolism of phenmetrazine, phendimetrazine and morazone,
      and their metabolites in urine. A sensitive, specific method using GC/NPD was
      applied to the determination of the rate of excretion of the drugs
      quantitatively, diphenylamina being used as the internal standard. The ether
      extract was derivatized with TFAA reagent, the metabolites and their TFA
      derivatives were identified by GC/NPD and GC/MSD methods. Norephedrine, cathine,
      ephedrine and pseudoephedrine in small amount were identified.

PMID- 1982039
TI  - Neurotransmitters and pre- and post-junctional receptors involved in the
      vasoconstrictor response to sympathetic nerve stimulation in rat tail artery.
AB  - The study was prompted by the need to re-evaluate, in view of the complexity of
      the evidence in the literature, the relative roles of different sympathetic
      transmitters and receptors in the contractile response of the tail artery of
      adult normotensive rats to electrical field stimulation. By the pharmacological
      approach employed, noradrenaline and adenosine 5'-triphosphate appeared to
      contribute to this response; the possible roles of other putative transmitters
      such as neuropeptide Y could not be examined due to lack of specific antagonists.
      Noradrenaline, clearly the main mediator, exerted both excitatory and inhibitory
      effects, acting in part via different receptors depending on the stimulus
      parameters. Thus, yohimbine and prazosin (alpha 2- and alpha 1-adrenoceptor
      antagonists, respectively) were about equally effective as inhibitors of the
      noradrenaline-mediated contractile response to stimulation with short trains
      and/or at low frequency, but the response caused by long trains and/or high
      frequency stimulation was much more strongly inhibited by prazosin than by
      yohimbine. As expected, yohimbine enhanced the [3H]noradrenaline overflow
      response to long but not to short stimulus trains, presumably because in the
      latter case the noradrenaline concentration in the relevant biophase was too low
      to activate the pre-junctional alpha 2-adrenoceptors. Finally, propranolol, an
      unselective beta-adrenoceptor antagonist, enhanced the neurogenic contraction,
      indicating that noradrenaline restricts this response by effects via post
      junctional beta-adrenoceptors. Adenosine triphosphate appeared to exert dual,
      excitatory as well as inhibitory, post-junctional effects. Thus, the P2x
      purinoceptor desensitizing agent, alpha, beta-methylene adenosine triphosphate,
      abolished the initial phase, but enhanced the amplitude of the neurogenic
      contraction, without affecting the nerve stimulation-induced overflow of
      [3H]noradrenaline. The results indicate that noradrenaline and adenosine
      triphosphate, the main mediators of the neurogenic contraction of this
      preparation, act in a more complex fashion than earlier thought; they argue
      against a significant direct contribution by other putative transmitters but do
      not exclude that such agents may act indirectly as modulators of this response.

PMID- 1982040
TI  - Effects of destruction of preoptic catecholaminergic nerve terminal on
      acupuncture analgesia.
AB  - The present work studied the effect of preoptic catecholamine on acupuncture
      analgesia. The catecholaminergic terminals were destructed by microinjection of 6
      hydroxydopamine into the preoptic area and the destruction was checked by
      fluorescence histochemical method. The results showed that the destruction of
      catecholaminergic terminals significantly enhance acupuncture analgesia,
      suggesting that the reduction of catecholamine content in the preoptic area may
      enhance acupuncture analgesia.

PMID- 1982041
TI  - Differential effects of various electrical parameters on peripheral and central
      nerve regeneration.
AB  - Optimal factors for small DC current electrical stimulation for nerve
      regeneration were studied. These studies are consistent with previous data and
      values expected for a return of function following Peripheral Nervous System
      (PNS) damage. This work represents the first detailed investigation of a dose
      response in the PNS using applied electric fields. As such, using the stimulator
      design described herein, we have found that a delivery of 1.4 microA DC (about
      8mV/cm field strength) to a nerve cuff will result in a more rapid increase of
      axon numbers in the distal slump with no detectable adverse influence of chronic
      delivery of current. Since it appears as though the regenerative capacity in the
      PNS and CNS is related to increased blood flow brought upon by the electric
      field, then it is important to consider this result in the final analysis of the
      mechanism of electric field induced nerve regeneration. Studies aimed at
      describing the mechanisms by which such regeneration occurs are now underway.

PMID- 1982042
TI  - Differentiation of acupuncture and nonacupuncture points by difference of
      associated opioids in the spinal cord in production of analgesia by acupuncture
      and nonacupuncture point stimulation, and relations between sodium and those
      opioids.
AB  - Antiserum of methionine-enkephalin (Met-Enk) applied intrathecally abolished
      acupuncture analgesia (AA) caused by low frequency stimulation of an acupuncture
      point (tibial muscle, APS) of rats, but antisera of leucine-enkephalin (Leu-Enk)
      and dynorphin (Dyn) did not. Antiserum of Dyn applied intrathecally abolished
      analgesia (NAA) produced by stimulation of a nonacupuncture point (NAPS) which
      was revealed by lesion in the analgesia inhibitory system (AIS), whereas antisera
      of Met-Enk and Leu-Enk did not. NAA was antagonized by the kappa-receptor
      antagonist, Mr2266, and analgesia was produced by the kappa-agonist, U50-488H, in
      the AIS lesioned rats. Potentials in the dorsal periaqueductal central gray (D
      PAG) evoked by APS were antagonized by naloxone and antiserum of Met-Enk, and
      those in the lateral PAG (L-PAG) evoked by NAPS were antagonized by Mr2266 and
      antiserum of Dyn. After adrenalectomy, AA, potentials in the D-PAG, and analgesia
      caused by stimulation (SPA) of the D-PAG were abolished 12 hour; and NAA,
      potentials in the L-PAG, and SPA of the L-PAG were abolished in 24 hour. All were
      then restored one hour after intravenous application of 1 ml of 5% NaCl solution.
      AA and NAA which were augmented for several hours before their abolition after
      adrenalectomy were not antagonized by naloxone nor M 2266, respectively. However
      naloxone and Mr2266 did antagonize AA and NAA, respectively, one hour after
      treatment with 1 ml of 5% NaCl solution.

PMID- 1982043
TI  - Clinical uses of P6 acupuncture antiemesis.
AB  - Having seen pregnant women pressing the P6 point as a preventative for morning
      sickness, stimulation of this point for 5-10 minutes by invasive (manual or
      electrical acupuncture) or non-invasive (transcutaneous electrical stimulation or
      acupressure) means was studied as an antiemetic. In well controlled studies it
      was shown that acupuncture administered before the opioid premedication
      significantly reduced postoperative sickness for 6-8 hours. Non-invasive methods
      were effective for a shorter period of time, with nausea and/or vomiting often
      occurring after 2 hours. To be effective the treatment has to be given before the
      opioid. Its effect can be abolished by local anesthesia. Stimulation of a dummy
      point near the elbow is ineffective. While acupressure reduces morning sickness,
      the pressure has to be applied for 5 minutes every 2 hours. There is probably a
      large psychological element in this. The most rewarding results are obtained when
      P6 stimulation is used in conjunction with standard antiemetics before cancer
      chemotherapy. Here again the invasive approach is more effective than non
      invasive. Recent studies have involved self-stimulation using a portable battery
      operated square wave stimulator fixed at 10 Hz, and a large EKG surface electrode
      on the P6 point. Stimulation is applied for 5 minutes every two hours. While
      modern antiemetics can control vomiting, they are relatively ineffective against
      nausea, but this can be controlled by regular use of the stimulator. The results
      are most promising.

PMID- 1982044
TI  - Simple non-invasive early detection and localization of specific cancer tissues
      of internal organs and differentiation of cancer tissue from surrounding areas
      infected by cancer related viruses, as well as evaluation of their micro
      circulatory condition & drug uptake using the BI-Digital O-Ring Test.
AB  - In 1984, the author first developed a simple, quick, non-invasive, economical
      method of detecting cancer in specific internal organs, using the Bi-Digital O
      Ring Test (BDORT), with a microscope slide of specific cancer of a specific
      internal organ as a reference control substance. The detection rate for cancer
      screening was much greater than with any standard diagnostic tests. When imaging
      was performed using the BDORT, the area of positive response to the cancer
      positive slide was often much greater than the actual size of the cancer itself.
      This was due to the fact that most of the cancer tissue of the lungs or digestive
      system contained viruses such as HTLV-3 (often found in adenocarcinoma of the
      lung, stomach, head of pancreas, and colon) or HTLV-1 (often found in small-cell
      carcinoma of the lung and certain types of leukemia). The extent of the virus
      positive area was often far greater than that of the cancer tissue itself and was
      distributed in a much greater area surrounding the cancer. For this reason, the
      virus alone showed a response which could be mistaken for cancer tissue. The
      author succeeded in differentiating the exact location of cancer tissue itself
      from surrounding cancer related virus (with or without other microbes) positive
      area by using a pair of identical microscope slides with the same cancer tissue.
      One of the slides was exposed to ultra-violet rays (peak wavelength of 253.7 nm
      mercury vapor atomic resonance spectral line) for 40 seconds-4 minutes. After
      this exposure, the BDORT response to the virus (with or without other microbes)
      associated with the cancer tissue was completely eliminated, while the response
      to the cancer tissue was maintained. Using an ultraviolet exposed cancer slide,
      the imaging of the part of the body which responded to this virus-free cancer
      slide indicated the actual location of the cancer tissue, which was often
      confirmed by standard X-ray or other imaging methods when the thickness of the
      tumor was relatively large. These cancers detectable by standard laboratory tests
      had strikingly weakening response to the BDORT (-3.5 and -4), with ultra-violet
      exposed cancer slide as well as for antibody of Oncogen C-fos. The smallest size
      of cancer tissue detected by this method was less than 1mm in diameter in the
      very early stage of the cancer, which usually cannot be detected by current
      laboratory tests.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1982045
TI  - Abstracts and short papers of the 6th International Symposium on Acupuncture and
      Electro-therapeutics. New York City, October 25-28, 1990.

PMID- 1982046
TI  - Importance of using soluble derivatives in assessing bilirubin interference: the
      example of gamma-glutamyltransferase.
AB  - In assessing possible in vitro interference from bilirubin on analytical methods,
      different results are to be expected from using either unconjugated (uB) or
      conjugated (cB) bilirubin as test materials, because of their different
      solubilities. In vitro interference of a synthetic soluble bilirubin derivative
      (ditauro-bilirubin, dtB) on gamma-glutamyltransferase activity measurement has
      been studied, in comparison with uB. In three out of five analytical
      methods/systems for the measurement of the enzyme activity, significantly higher
      (negative) interference was observed in the presence of the soluble derivative.
      Whichever the mechanism for the observed effect, the opportuneness of using
      soluble derivatives in order to assess bilirubin interference is pointed out:
      pathological serum specimens, submitted for laboratory investigations, are indeed
      frequently loaded with soluble bilirubin conjugates.

PMID- 1982047
TI  - [Editorial symposium. Surgery of morbid obesity].

PMID- 1982048
TI  - Clinical correlations of the neurobiological changes of aging.
AB  - Increasing age is associated with increased risk of developing both dementia and
      depression; both conditions appear to be associated with structural changes in
      the cerebral cortex. In depression, there was evidence for regional alterations
      in cortical neurons either as a result of the disease or its treatment. In
      Alzheimer's disease, a key change is likely to be either shrinkage or loss of
      corticocortical pyramidal neurones which probably use glutamate as their
      transmitter. The putative pathogenic role of glutamate and energy metabolism, as
      well as an approach to treatment of symptoms are outlined.

PMID- 1982049
TI  - Restriction site variation, length polymorphism and changes in gene order in the
      mitochondrial DNA of the yeast Kluyveromyces lactics.
AB  - The purpose of this work was to compare mitochondrial DNA restriction
      endonuclease patterns in strains of the yeast Kluyveromyces lactis, from
      different sources, to see how conserved is the organization of this organellar
      genome. The mitochondrial DNA of five independently-isolated strains and one of
      unknown origin were compared. Strains NRRL Y-1205, NRRL Y-8279 and NRRL Y-1140
      gave identical patterns. Strain NRRL Y-1564 showed an insertion, with respect to
      the other three, of approximately 1250 bp. Strain W600B had also an insertion
      with extra restriction sites for EcoRI, HpaI, HaeIII, HincII and XbaI. On the
      other hand, strain Y-123 showed a restriction pattern quite different from the
      others. Sequences putatively encoding apocytochrome b, ATPase subunit 9 and
      ribosomal RNA large subunit, were localized on the physical maps of three
      strains. Results demonstrated that the order of these three genes shows a common
      feature in strains W600B and WM37 (auxotroph of Y-1140) but a different
      distribution in WM27 (auxotroph derived from Y-123). All these facts explain the
      extensive intraspecific polymorphism observed in the mtDNA of this yeast.

PMID- 1982050
TI  - [Study of tall stature in children. Low paradoxically low answer of growth
      hormone to stimulation with ornithine].

PMID- 1982051
TI  - Liver function in normal pregnancy.
AB  - Liver function tests were measured in a longitudinal study of 64 women throughout
      normal pregnancy. Standard liver function tests and postprandial levels of
      cholesterol, triglycerides, protein and albumin were measured at each visit.
      Serum alkaline phosphatase, cholesterol and triglyceride levels increased
      significantly throughout pregnancy (p less than 0.001) while serum transaminases
      and bilirubin remained within the normal range. Total protein and albumin levels
      decreased significantly (p less than 0.001).

PMID- 1982052
TI  - International Symposium. Mathematical models of cellular processes. November 19
      23, 1989, Holzhau.

PMID- 1982053
TI  - Effectiveness of cast-joined Ni-Cr-Be structures.
AB  - This study tested the load transfer effectiveness of cast-joined structures under
      flexural loading conditions. Bars of Rexillium III alloy (Ni-Cr-Be) were tested
      under four-point bending conditions in an Instron testing machine. Six specimens
      were prepared for each of five interlocking designs. After wax elimination of the
      investment mold, new metal was cast into the central interlock area. Strain
      gauges were bonded across the interfaces between the as-cast and secondary cast
      structures on the bottom surface, and the specimens were loaded to failure in a
      four-point-bending fixture. Failure was assumed at a strain level of 0.1%, which
      corresponds to the tensile failure strain of feldspathic porcelain. Three as-cast
      bars were tested as controls. The average failure load of an interlock design
      used by Weiss and Munyon was significantly higher (P less than 0.05) than that of
      the remaining four designs but was significantly lower (P less than 0.05) than
      that of the solid bar. At the critical strain level of 0.1%, the load-transfer
      effectiveness of the Weiss and Munyon design was less than 22%. The results
      suggest that the cast-joining technique may increase the risk of failure in
      clinical situations where high flexural stresses exist.

PMID- 1982054
TI  - In-vivo metabolism of 4-substituted arylpiperazines to pharmacologically active 1
      arylpiperazines.
AB  - A common metabolic process of 4-substituted arylpiperazine pharmacological agents
      is cleavage of the side-chain to yield 1-arylpiperazines. These metabolites are a
      well-known class of centrally active compounds and their formation may therefore
      be a pharmacologically significant pathway, at least in certain species, for
      derivates that undergo extensive cleavage of the arylpiperazine side-chain. Of
      pharmacological relevance is the observation that they may have a spectrum of
      pharmacological actions different from the parent compound(s). As illustrated by
      the anxiolytic agent buspirone, its derivates gepirone and isapirone and their
      common metabolite 1-(2-pyrimidinyl)-piperazine (PmP), parents drug(s) and
      metabolite may have quite different mechanism of action. In other cases, the 1
      arylpiperazine metabolite and its parent drug(s) may act antagonistically (i.e. 1
      (m-chlorophenyl)-piperazine, mCIPP, and its parent drugs trazodone and
      etoperidone). The kinetic properties of 1-arylpiperazine metabolites may differ
      from those of the parent compound, particularly in relation to the extent to
      which they enter the brain, the site of action of most of these compounds. The
      examples given although limited, provide evidence that kinetics and
      pharmacological studies on 1-arylpiperazine metabolites are important in seeking
      to understand the mechanism of action of the 4-substituted derivatives and in
      extrapolating pharmacological finding from animals to man.

PMID- 1982055
TI  - A microiontophoretic study of the role of excitatory amino acids at the afferent
      synapses of mammalian inner hair cells.
AB  - The results presented indicate that L-glutamate is involved in mediating
      excitatory afferent neuro-transmission in the mammalian cochlea. Glutamate
      applied directly into the subsynaptic inner hair cell region of the adult guinea
      pig with the aid of microiontophoretic techniques evoked neuronal firing. By
      using competitive antagonists for glutamate receptors, a further study was
      carried out in order to identify possible receptor types. Such included N-methyl
      D-aspartate (NMDA), kainate and quisqualate receptors, which are defined by
      selective agonist action. The glutamate-induced cochlear firing rate was
      antagonized by D-2-amino-7-phosphonoheptanoate (AP-7), suggesting that the
      receptor involved is of the NMDA type. Further studies with glutamic acid
      diethylester (GDEE) showed that glutamate-induced activity could also be blocked
      by this substance. Since GDEE depresses responses to quisqualate, non-NMDA
      receptors also have to be taken into consideration.

PMID- 1982056
TI  - Blockade of synaptic transmission from hair cells to auditory afferent nerves by
      6-cyano-2,3-dihydroxy-7-nitroquinoxaline, a selective non-NMDA receptor
      antagonist.
AB  - 6-Cyano-2,3-dihydroxy-7-nitroquinoxaline (CNQX) is a new, potent and selective
      competitive antagonist for the non-N-methyl-D-aspartate (non-NMDA) type of
      excitatory amino acids receptors. We studied the effect of CNQX on the compound
      auditory nerve action potential (CAP), cochlear microphonics (CM), summating
      potential (SP) and endocochlear potential (EP). CNQX in doses of 10-20 microM
      reduced the CAP magnitude and increased the N1 latency without affecting the CM,
      SP, or EP. Parallel shifts of CAP amplitude- and latency-intensity functions were
      observed. The CAP suppressed by 10 microM CNQX was completely reversed by a 10
      min washout with artificial perilymph. As 10 microM and 20 microM CNQX seem to
      exert a selective antagonism for non-NMDA receptors, results indicate that non
      NMDA receptors play a major role in synaptic transmission from hair cells to
      auditory afferent nerves.

PMID- 1982057
TI  - [Treatment with somatostatin of variceal digestive hemorrhage: a one-year
      prospective].
AB  - Twenty-two patients with variceal bleeding were treated with somatostatin,
      receiving a bolus of 250 mcg followed by an infusion at a rate of 250 mcg/hour.
      Bleeding stopped in sixteen patients (72.7%). Definitive control was attained in
      13 patients (59.2%). Mortality was 31.8%. Somatostatin was not effective in
      patients with large varices, jet bleeding and hepatic insufficiency. Only minor
      side effects were recorded in four patients (18.2%).

PMID- 1982058
TI  - Characterization of the hemodynamic activities of fenoldopam and its enantiomers
      in the dog.
AB  - Fenoldopam (SK&F 82526) is a potent and selective dopamine DA-1 agonist with
      demonstrated renal vasodilator and antihypertensive activities in experimental
      animals and humans. Fenoldopam is a racemic mixture of two enantiomers, SK&F R
      82526 and SK&F S-82526. The R-enantiomer is uniformly reported to be more potent
      than the racemate; in contrast, there is controversy regarding potency of the S
      enantiomer. In these studies, the renal and systemic hemodynamic activities of
      fenoldopam and its enantiomers are characterized in anesthetized,
      phenoxybenzamine-treated dogs. The results show that the renal and systemic
      vasodilator activities of fenoldopam are properties of the R-enantiomer; the S
      enantiomer is essentially inactive. The renal and systemic vasodilator properties
      of SK&F R-82526 are antagonized in a competitive fashion by the DA-1 antagonist,
      SK&F R-83566, but not the DA-2 antagonist, domperidone. Ganglionic blockade did
      not attenuate renal vasodilation associated with SK&F R-82526. Thus, the
      mechanism of SK&F R-82526-associated vasodilation, like that previously
      established for fenoldopam, is via stimulation of postganglionic DA-1 receptors.

PMID- 1982059
TI  - Comparative effects of celiprolol, propranolol, oxprenolol, and atenolol on
      respiratory function in hypertensive patients with chronic obstructive lung
      disease.
AB  - The aim of the study was to compare the pulmonary effects of four beta-blockers
      with different ancillary properties: propranolol (non-beta 1 selective without
      ISA), oxprenolol (non-beta 1 selective with ISA), atenolol (beta 1 selective),
      and celipropol (beta 1 selective with mild beta 2-agonist and alpha 2-antagonist
      activity) in hypertensive patients with chronic obstructive lung disease. Ten
      asthmatic patients, all males, aged 50-66 years were studied. Entry criteria were
      a) DBP greater than or equal to 95 mmHg and less than or equal to 115 mmHg; b)
      FEV1 less than 70% of the theoretical values; c) FEV1 increase of at least 20%
      after salbutamol inhalation (200 micrograms). After a 2-week washout period on
      placebo, each patient received propranolol (80 mg/day), oxprenolol (80 mg/day),
      atenolol (100 mg/day), and celiprolol (200 mg/day) for 1 week, according to a
      randomized, cross-over design. At the end of the washout and of each treatment
      period, airway function, assessed by FEV1, FVC, and FEV1%, was evaluated by
      spirometry both in the basal condition and after salbutamol inhalation. Unlike
      propranolol and oxprenolol, which significantly reduced FEV1 and inhibited the
      bronchodilator response to inhaled salbutamol, atenolol and celiprolol did not
      significantly affect respiratory function and did not antagonize salbutamol
      effects. Celiprolol more closely approached placebo in its respiratory effects
      than did atenolol, although the differences were not statistically significant.

PMID- 1982060
TI  - Human neuroblastoma tumor cell lines correspond to the arrested differentiation
      of chromaffin adrenal medullary neuroblasts.
AB  - We have examined the hypothesis that nonhematopoietic malignancies may contain
      cells corresponding to those which occur during the differentiation of tissue
      precursors. Neuroblastoma, an embryonal tumor of the adrenal medulla, was studied
      because of its well described ability to differentiate both in vivo and in vitro.
      We examined the expression of four genes during development of the human adrenal
      medulla: tyrosine hydroxylase, chromagranin A, pG2, and beta-2-microglobulin. The
      sequential expression of these genes by adrenal neuroblasts marks successive
      stages during maturation of the chromaffin lineage. We also observed a population
      of neuroblasts during adrenal medullary development that did not express any of
      these four genes, suggestive of adrenal medullary cells differentiating along
      nonchromaffin lineage(s). We then evaluated 27 neuroblastoma cell lines for the
      expression of these genes and found that 24 expressed chromaffin markers, with 19
      of these mimicking the pattern of gene expression found during development. Three
      cell lines did not express tyrosine hydroxylase, chromogranin A, or pG2,
      consistent with either a very undifferentiated neural crest cell or maturation
      along a nonchromaffin lineage. These data indicate that neuroblastoma tumor cells
      correspond to adrenal neuroblasts arrested during morphogenesis of the adrenal
      medulla and raise the possibility that malignant transformation of cells at
      different stages of tissue maturation may contribute to the diversity that
      characterizes tumors of solid tissues.

PMID- 1982061
TI  - Characterization of the 5' end of the growth-regulated Syrian hamster CAD gene.
AB  - The carbamoylphosphate synthetase-aspartate transcarbamylase-dihydroorotase (CAD)
      gene encodes a tri-functional protein catalyzing the first three steps in de novo
      pyrimidine biosynthesis. Studies correlating CAD gene expression with cellular
      proliferation indicate the importance of understanding the regulation of the CAD
      gene. As a first step, the structure of the promoter region of the Syrian hamster
      CAD gene has been determined. Sequence analysis of 1671 base pairs of DNA
      revealed that the CAD promoter region is very GC rich. Primer extension analysis
      indicated that the transcription initiation site of the CAD gene is downstream
      from two GC boxes (consensus binding sites for the transcription factor Sp1).
      There is no TATA box appropriately spaced upstream from the transcription
      initiation site. Using RNase protection mapping, S1 nuclease analysis, and
      comparison to consensus splice donor/acceptor sites, the 5' end of the CAD gene
      has been determined to consist of a 241-base pair first exon, a 187-base pair
      first intron, a 140-base pair second exon, and a second intron that extends at
      least three kilobase pairs. Using conditions optimized for this GC-rich promoter,
      accurate transcription can be achieved in vitro. Analysis of CAD promoter
      deletions indicated that sequences extending only 114 base pairs upstream and 225
      base pairs downstream from the transcription initiation site are sufficient for
      accurate and efficient transcription in vitro. DNase I footprinting reactions
      using this promoter fragment have identified three regions that bind proteins in
      a HeLa nuclear extract.

PMID- 1982062
TI  - Familial occurrence of cryptorchidism.
AB  - A case of Cryptorchidism involving a father and all his four sons who are product
      of a nonconsanguineous marriage has been described. From a review of the
      literature, as well as evidence derived from the family history, it is suggested
      that the mode of inheritance may be autosomal dominant with incomplete penetrance
      or multifactorial.

PMID- 1982063
TI  - Amplification of cellular oncogenes: a predictor of clinical outcome in human
      cancer.
AB  - Increased dosage of cellular oncogenes resulting from amplification of DNA is a
      frequent genetic abnormality of tumor cells and the study of oncogene
      amplification has been paradigmatic for the usefulness of molecular genetic
      research in clinical oncology. Certain types of human tumors carry an amplified
      cellular oncogene at frequencies of up to 50-60%. Human neuroblastoma has been
      prototypic for the importance of oncogene amplification in tumorigenesis, and
      evidence is emerging that amplification may be an early event involved in a more
      malignant form of this cancer. It is unclear at which stage amplification plays a
      role in other cancers. Amplification of cellular oncogenes is a good predictor of
      clinical outcome in some human malignancies.

PMID- 1982064
TI  - Molecular mapping of deletion sites in the short arm of chromosome 3 in human
      lung cancer.
AB  - We used 10 restriction fragment length polymorphism (RFLP) probes spanning the
      length of the short arm of chromosome 3 (3p) to map deletion sites in human lung
      cancer. Two approaches were used. 1) When a patient's tumor and normal tissue
      were available, loci with allelic heterozygosity in the normal tissue were tested
      for loss of alleles at 3p. 2) When the corresponding normal tissue was not
      available, the frequency of heterozygosity at each locus in a panel of tumors was
      compared to the corresponding published frequencies in nontumor tissue of healthy
      individuals or patients with lung cancer. In 14 small cell lung carcinomas (SCLC)
      with normal DNA for comparison, allele loss was found at all heterozygous loci,
      with one exception at a locus near the 3p centromere (D3S4). In the total of 53
      SCLCs, which included tumors without paired normal tissue, frequency of
      heterozygosity was significantly reduced in all 10 3p loci. Three loci, DNF 15S2,
      RAF1, and D3S18, were homozygous in all tumors in the SCLC panel. These loci,
      which are in regions 3p21 and 3p25, may thus be involved in the origin or
      evolution of SCLC. We also investigated 24 non-SCLC tumors. In this panel,
      frequency of heterozygosity was significantly reduced at seven of the 10 loci
      tested. Comparison of the results shows that the pattern of allele loss on 3p is
      different in SCLC and non-SCLC, suggesting a difference in pathogenesis at the
      genetic level.

PMID- 1982065
TI  - [Regulation of secretion and synthesis of gastrointestinal hormones: studies with
      cultured gut endocrine cells].
AB  - Small number of endocrine cells are diffusely distributed in the gut mucosa.
      Studies on their secretory mechanisms have been further complicated by numerous
      neural, paracrine, and endocrine factors affecting their response. Recent
      technical development for isolation and culture of gut endocrine cells has
      circumvented these problems and enabled to study their receptors, signal
      transduction mechanism, and biosynthesis of gut hormones. In this review, current
      progress made in the cellular physiology of gut endocrine cells is summarized.

PMID- 1982066
TI  - Thy-1-positive dendritic epidermal cells contain a killer protein perforin.
AB  - The killer cell characteristics of Thy-1-positive dendritic epidermal cells (Thy
      1+ DEC) were examined. Four Thy-1+ DEC clones which were established from athymic
      nude mice exhibited spontaneous or lectin-redirectable cytotoxic activity against
      some murine tumor cell lines in a 4 h 51Cr-release assay. A colorimetric assay
      for benzyloxycarbonyl-L-lysine-thiobenzyl ester esterase revealed a strong serine
      esterase activity expressed in all cell clones. In addition, Northern blot
      analysis using a murine perforin cDNA probe revealed that all four Thy-1+ DEC
      clones expressed abundant mRNA for perforin, as do most killer T cells. More
      importantly, immunocytochemical staining with an anti-perforin monoclonal
      antibody revealed that not only all four Thy-1+ DEC clones but also a part of
      freshly isolated Thy-1+ DEC from normal and nude mice contained perforin. These
      results demonstrate that Thy-1+ DEC exhibit typical killer cell characteristics
      in vitro and in vivo. These data also suggest that Thy-1+ DEC may play a
      cytotoxic role in protecting the integrity of skin from infection or neoplastic
      transformation.

PMID- 1982067
TI  - Activation of protein kinase C is crucial in the regulation of ICAM-1 expression
      on endothelial cells by interferon-gamma.
AB  - ICAM-1 (CD54) is expressed on endothelial cells and serves as an important ligand
      for the white cell adhesion molecule CD11a/CD18 (LFA-1). Many studies have
      demonstrated that increased numbers of white cells binding to endothelial cells
      correlate with the level of ICAM-1 expression on endothelial cells. Several
      cytokines, including IFN-gamma, increase ICAM-1 expression in cultured human
      endothelial cells. We have analysed the second intracellular messenger pathways
      involved in IFN-gamma-induced up-regulation of ICAM-1 expression in endothelial
      cells. IFN-gamma induced a rapid activation of phospholipase C, leading to a
      breakdown of phosphoinositoldiphosphate (PIP2) into diacyglycerol (DAG) and
      inositoltriphosphate (IP3). DAG is a natural activator of the protein kinase C
      pathway. We were able to show that the effect induced by IFN-gamma could be
      inhibited by a protein kinase C inhibitor, H7, in a dose-dependent manner and
      mimicked by PMA, which stimulates protein kinase C. IFN-gamma induced a 5-fold
      translocation (activation) of protein kinase C from the cytosol into the
      endothelial cell membrane. Elevation of the IP3 levels led to activation of the
      calcium-dependent pathway. An inhibitor of calcium calmodulin, W7, decreased the
      IFN-gamma induced ICAM-1 expression, and addition of calcium ionophore to
      endothelial cells could replace IFN-gamma in the up-regulation of ICAM-1.
      Finally, IFN-gamma caused a significant increase in the calcium flux of
      endothelial cells. cAMP and cGMP had no effect on the regulation of ICAM-1
      expression on cultured human endothelial cells.

PMID- 1982068
TI  - Induction of human TCR gamma delta + and TCR gamma delta-CD2+CD3- double negative
      lymphocytes by bacterial stimulation.
AB  - When human blood mononuclear cells (MNC) were incubated with heat-killed
      bacteria, proliferation of MNC was observed 5 days after stimulation, showing a
      peak on day 7. Interestingly, the bioassay of the culture supernatant and
      Northern blot analysis of mRNA demonstrated that no IL-2 production was
      associated with these proliferative responses. The induced lymphoblasts consisted
      predominantly of TCR gamma delta + (22.4 +/- 9.3%) and TCR gamma delta-CD2+CD3
      (33.2 +/- 11.8%) double negative lymphocytes (n = 10), which were initially minor
      populations (less than 10%) in freshly isolated MNC. The prominent induction of
      TCR gamma delta + cells was confirmed by Northern blot analysis. TCR gamma delta
      + cells induced by bacterial stimulation seemed to generate from lymphocytes
      lacking the apparent expression of gamma delta TCR. The inducing capability for
      double negative cells is present in a large number of species of bacteria,
      especially Gram-positive bacteria. Gel filtration analysis of ultrasonicated
      filtrates of Staphylococcus aureus and Streptococcus pyogenes revealed that a
      substance with an Mr of 25-26 kd could be substituted for whole bacterial
      particles in the cell proliferative responses. In contrast to the purified
      protein derivative (PPD)-induced response, the response described here was
      inducible in the cord blood of neonates who had not yet been exposed to the
      corresponding bacterial infection. The physicochemical properties of the
      sonicated filtrates were different from those of PPD. These results suggested
      that the present phenomenon may be nonspecific, polyclonal (or oligoclonal)
      activation of TCR gamma delta + and TCR gamma delta -CD2+CD3- cells by bacterial
      stimulation.

PMID- 1982069
TI  - Angel dust and other antagonists. Neurobiology of the NMDA Receptor: from
      Chemistry to Clinic, sponsored by the Society for Neuroscience, University of
      Pittsburgh, Pittsburgh, PA, USA, October 27-28, 1989.

PMID- 1982070
TI  - The maternal-effect gene fsh is essential for the specification of the central
      region of the Drosophila embryo.
AB  - The maternal-effect gene, female sterile (1) homeotic (fsh), has been implicated
      in the determination of segmental organization and identity. We have analyzed the
      spatial patterns of expression of several segmentation and homeotic genes in fsh
      deficient embryos. We observed perturbations in the expression of the
      Ultrabithorax gene in parasegments 6, 7, and 8, consistent with the domain in
      which homeotic transformations occur in adults derived from such embryos.
      Further, the expression of the gap gene Kruppel and the pair-rule gene even
      skipped is altered, especially in the central region of the embryo. Our results
      suggest that the defects in segmental organization in fsh-deficient progeny are
      mediated primarily but not exclusively through a restriction of the domain of
      Kruppel expression.

PMID- 1982071
TI  - The DNA binding specificity of the Drosophila fushi tarazu protein: a possible
      role for DNA bending in homeodomain recognition.
AB  - Segmentation in Drosophila melanogaster is controlled by a network of interacting
      genes, many of which encode a homeodomain that confers sequence-specific binding
      to DNA. One of these, fushi tarazu (ftz), is a transcription factor that
      regulates a number of segmentation and homeotic genes, including Antennapedia
      (Antp). To determine the DNA binding specificity of the ftz homeodomain, we
      performed DNase I footprint analysis on ftz protein binding sites located near
      the two Antp promoters using a beta-galactosidase/ftz fusion protein synthesized
      in E. coli. A consensus sequence for the fusion protein's preferred binding site
      was derived from 19 sites. The consensus sequence contains an ATTA motif, as do
      the reported consensus sequences for the engrailed (en), even-skipped (eve), and
      bicoid (bcd) Drosophila homeodomain proteins. We propose DNA bending as an
      explanation for the presence of a shared motif between proteins with divergent
      recognition helices: according to this model, bases in ATTA would not directly
      contact amino acid side chains of the recognition helix but rather would be
      necessary for bending of the DNA around the homeodomain, perhaps facilitating
      important protein-DNA contacts.

PMID- 1982072
TI  - The role of autophosphorylation in modulation of erbB-2 transforming function.
AB  - The product of the erbB-2 gene is a 185-kD receptor-like glycoprotein. erbB-2
      gp185 displays constitutive tyrosine kinase activity and transforms NIH 3T3 cells
      when expressed 100-fold over the normal levels. We have analyzed the role of
      tyrosine kinase function and of receptor autophosphorylation in the regulation of
      erbB-2 biological activity. Abolition of erbB-2 gp185 tyrosine kinase function
      resulted in complete loss of its transforming activity and the absence of in vivo
      tyrosine phosphorylation. The steady-state content of phosphotyrosine in erbB-2
      gp185 was found to be solely dependent on receptor autophosphorylation and to be
      dependent on the specific enzymatic activity of the erbB-2 protein. The major
      sites of erbB-2 autophosphorylation were shown to be in its COOH-terminal domain.
      Biological analysis of erbB-2 mutants containing either individual or multiple
      Tyr----Phe substitutions at the potential sites of autophosphorylation revealed
      that autophosphorylation upregulates erbB-2 gp185 transforming activity.
      Autophosphorylation did not modulate receptor turnover. A Tyr----Phe substitution
      of erbB-2 Tyr-877 homologous to pp60c-src Tyr-416 did not alter erbB-2 biological
      and biochemical properties, thus excluding the possibility that phosphorylation
      of this residue, located in the kinase domain, modulates erbB-2 gp185 catalytic
      function. Hence, autophosphorylation of tyrosine residues localized in its COOH
      terminus appears to be required for optimal coupling of erbB-2 gp185 with its
      mitogenic pathway.

PMID- 1982073
TI  - Up the down staircase. Signal Transduction and Gene Activation in Development: a
      UCLA Symposium sponsored by Amgen, Steamboat Springs, CO, USA, March 31-April 7,
      1990.

PMID- 1982074
TI  - The B cell grows up. B-lymphocyte Development: a UCLA Symposium sponsored by
      Immunex and Ortho, Park City, UT, USA, March 31-April 6, 1990.

PMID- 1982075
TI  - Imports, exports, and quality control. Intracellular Routing of Protein
      Molecules, sponsored by the Karolinska Institute, Center for Biotechnology,
      Huddinge, Sweden, May 18-19, 1990.

PMID- 1982076
TI  - Thyroid hormone and neoplastic transformation.

PMID- 1982077
TI  - [The participation of cholinergic structures at different levels in shaping the
      immediate adaptation of the pancreas to food quality in ontogeny].
AB  - The experiments on rats showed that the urgent enzymatic adaptations of the
      pancreas to the quality of food have not been inherent, but have been created in
      the ontogeny. These adaptations are usually absent during transition to the
      definitive feeding (23rd day of life). Adaptation for protein stimulant appears
      in the moment of taking away of mother (30th day of life) and becomes persistent
      for protein and fat stimulants by the 90th day of life (adult rats). The blockade
      of different levels' cholinergic structures prevents the normal development of
      urgent specific pancreas adaptations in all investigated ages.

PMID- 1982078
TI  - [The effect of the deprivation of paradoxical sleep on the rotational and
      stereotyped behavior induced by selective agonists of the dopamine receptors].
AB  - The ability of selective D1 and D2 agonists of dopamine (DA) receptors SKE-38393
      and Ly-171555 to induce rotational and stereotypes behaviour were studied in rats
      with unilateral striatal kainic acid lesion before and after procedure of REM
      sleep deprivation (REMSD) lasting for 5 days. It was found that REMSD SKF-38393
      given along induced the ipsilateral rotation. REMSD increased the circling and
      decreased an oral stereotype simultaneously when SKF-38393 and Ly-171555 were
      given together. The depletion of brain DA in part with alpha-methyl-p-tyrosine
      (AMPT) in nondeprived rats fails to influence the rotational behaviour and
      stereotype when SKF 38393 was injected 30 min following Ly-171555. After REMSD
      the AMPT pretreatment prevents the rotational behaviour caused by Ly-171555 which
      restores SKF-38393. The results suggest that prolonged REMSD may induce
      nonidentical changes in the sensitivity of the postsynaptic D1 and D2 receptors.

PMID- 1982079
TI  - [THe selective effect of neuroleptics on a dopamine-dependent behavioral disorder
      in rats in the extrapolation escape test].
AB  - The low doses of neuroleptics restored the ability of 1-DOPA treated rats to
      escape behaviour from acute stress situation (in the extrapolation escape test).
      Non-antipsychotic benzamides and phenothiazine, antidepressants and
      benzodiazepine tranquilizers were inactive. On the whole, the effectiveness of
      neuroleptics was in accordance with clinical data. The loss of ability to escape
      in 1-DOPA treated rats was accompanied by stereotypes hyperlocomotion in the
      water. Various psychotropic drugs decreased only hyperactivity without the
      influence on escape behaviour. Both forms of behavioral pathology were prevented
      by central aromatic acid decarboxylase inhibitor. However, the loss of ability to
      escape behavior only is selective and sensitive to neuroleptics action.

PMID- 1982080
TI  - [The role of fibronectin in the pathogenesis of meningococcal infection].
AB  - We have characterized an interaction of 20 strains of Neisseria meningitidis
      serogroups A, B, C, 29E, W-135 and Z with immobilized fibronectin of human
      plasma. The adhesion of meningococci to fibronectin was determined by the extent
      of piliated cells and did not depend on the meningococcal serogroup. Binding of
      non-piliated or weakly piliated strains (2-5% of piliated cells in the stock) was
      sufficiently greater than those piliated (8-10%), where the adhesion to
      fibronectin was not at all observed. The examination of two well-piliated strains
      showed that the loss of pili resulted in the increase of bacterial adhesion to
      fibronectin. Constants of association and dissociation of piliated and non
      piliated strains to fibronectin were calculated. The role of meningococci
      fibronectin interaction in the pathogenesis of meningococcal infection is
      discussed.

PMID- 1982081
TI  - [Pili determined by the tra genes of F-like plasmids].
AB  - The study of structural and functional features of plasmid-specific pili
      synthetized by E. coli cells under control of 27 F-like plasmids was performed.
      All the plasmids determined the pili of "flexible" type which were classified
      into 3 groups on the basis of difference in cell sensitivity to pili-specific
      phages f1, f2, Q. The possible role of transposons in the variation of pili
      functional properties was supposed.

PMID- 1982082
TI  - [The epiphysis (pineal body) and the APUD system].
AB  - Light and electron microscopic studies were conducted on 10 humans who died of
      the different cardiac diseases; and 20 guinea pigs pineal glands. Pinealocytes or
      secretory cells of the pineal gland have morphological likeness with the APUD
      system cells. They have a well-developed endoplasmic reticulum, Golgi complex,
      mitochondrial component and in cytoplasm dense-core vesicles are discovered.
      However the pinealocytes have a neuron-like structure and they are not separate
      cells as apudocytes, but they are a principal component of the pineal parenchyma
      in which pinealocytes are in tight interactions with glia, blood vessels and
      nerve terminations. Analysis of morphological and functional similarity and
      difference between pinealocytes and apudocytes allows to consider pineal gland as
      an APUD organ. A circadian rhythmicity of some secretory vesicles in pinealocytes
      of the guinea pig has been established.

PMID- 1982083
TI  - [GABAergic modulation of amnesic trace reproduction by activation of the
      dopaminergic system].
AB  - Features of amnesia trace reactivation by activation of different links of
      dopaminergic system synaptic apparatus following the change of benzodiazepine,
      GABAA and GABAB receptors activity are found in experiments in mice. Diazepam
      pretreatment increases bupropion effectiveness, prolongs duration of enhanced
      passive avoidance response retrieval during D-1 and D-2 receptors activation by
      (+)3-PPP and decreases both characteristics under selective D-2 receptor
      activation by quinpirole. Activation of GABAA and GABAB receptors induces the
      attenuation of quinpirole effect and the duration of (+)3-PPP action.

PMID- 1982084
TI  - Are neuronal precursor cells committed to coexpress different neuroactive
      substances in early amphibian neurulae?
AB  - Considering the initial expression of neurotransmitters and neuropeptides
      immediately after neural induction in amphibian embryos, we previously pointed
      out that a neuronal cell population emerges from neural plate (NP) and neural
      fold (NF) expressing very early specific cholinergic, catecholaminergic,
      GABAergic and peptidergic traits. The purpose of the present work was to
      investigate the extent to which the neuroblasts that are present in the
      neurectoderm immediately after gastrulation are committed to give rise to
      multiple subsets of neurons containing various combinations of neuroactive
      transmitters rather than to different subpopulations of neurochemically
      homogeneous neurons. By means of double immunocytochemical localization with a
      monoclonal TOH-antibody and polyclonal antibodies against GABA or somatostatin,
      no coexistence of neurotransmitters and neuropeptide was ever found in neuronal
      subpopulations arising in vitro from NP or NF. The early emergence, under the
      same conditions, of distinct neuronal subpopulations as a consequence of neural
      induction strongly suggests that, at the gastrula stage, the neural precursor
      population most probably does not constitute a homogeneous set of cells.

PMID- 1982085
TI  - [Dissemination of arboviruses transmitted by mosquitoes in Czechoslovakia and the
      epidemiologic consequences].
AB  - In Czechoslovakia three new arboviruses isolated from mosquitoes were discovered-
      Tahyna, Calovo and Lednice--which circulate on our territory. The submitted paper
      summarizes the results of long-term oecological studies of these viruses, in
      particular their vectors and hosts. The differences between individual viruses in
      this respect are very marked and from them also differences in the circulation of
      these viruses follow. There are also very marked differences in their
      distribution, as apparent from the isolation of 83 strains of the viruses from
      more than 263,000 mosquitoes 61 of whom belong to the Tahyna virus, 15 to the
      Calovo virus and 7 to the Lednice virus. The Tahyna virus was isolated from 8
      mosquito species, virus Calovo and Lednice only from a single one. While vectors
      of the Tahyna virus, mainly from the genus Aedes, are widespread as far as
      biotypes, radius of action and hosts are concerned, and they attack man, vectors
      of the Calovo and Lednice virus--Anopheles maculipennis s.l. and Culex modestus-
      have much more restricted activities as regards biotype, radius of action, hosts
      and contact with humans. The above reasons explain also the high prevalence of
      antibodies against the Tahyna virus in the population living in the natural focus
      of this virus and the relatively high number of diseases, in particular in
      children, where every seventh influenza--like case and every fifth case with
      manifestations of meningoencephalitis can be ascribed to this virus. The low
      prevalence of antibodies the Calovo virus in humans is explained by the marked
      zoophilia of vectors of this virus.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1982086
TI  - [Mechanism of action of benzodiazepines].

PMID- 1982087
TI  - [Summaries of reports presented at the 18th conference of the Commission for
      Experimental Cardiology of the J.E. Purkinje Physiological Society, Cesky
      Krumlov, October 4-6 1989].

PMID- 1982088
TI  - New dopamine receptor agonists in heart failure and hypertension. Implications
      for future therapy.

PMID- 1982089
TI  - Calcium antagonists in hypertension. Proceedings of a symposium. Bangkok,
      Thailand, February 9, 1990.

PMID- 1982090
TI  - Mutual priming effects of GHRH and arginine on GH secretion: informative
      procedure for evaluating GH secretory dynamics.
AB  - To establish a single and reliable test for evaluating GH secretion, we examined
      successive GH provocation by two agents with different modes of action: GHRH and
      arginine (Arg). In 4 normal subjects, a bolus injection of 50 micrograms of GHRH
      followed by 0.5 g/kg Arg infusion after 90 min evoked two GH peaks and the
      priming of the GHRH potentiated Arg-induced GH peak by 88% of that by Arg alone.
      In contrast, Arg pretreatment suppressed the GHRH-induced GH peak to a level of
      15%. This inhibitory effect of Arg priming was not recovered by an increase in
      the GHRH dose (100 micrograms) or by prolongation of the GHRH injection period to
      180 min. During Arg infusion, plasma somatostatin (SRIH) was significantly
      reduced and there was a linear correlation between Arg-induced GH peaks and basal
      TSH levels. This suggests that GH release by Arg is mediated by suppression of
      hypothalamic SRIH. One subject showed a blunted GH peak in response to GHRH but a
      normal peak in response to Arg repeatedly, suggesting an endogenous hypertonicity
      of SRIH. In 4 other normal subjects, the effect of endogenous GH fluctuation on
      the GHRH-Arg test was examined in the morning, afternoon and evening. The GH
      secretory profile was fairly consistent in individuals, but in 2 of them, GH
      response to GHRH was exaggerated in the evening and Arg-unresponsiveness ensued.
      This potentiation of GH release appears to be due to an increase in endogenous
      GHRH secretion or a decrease in SRIH tone. The GHRH-Arg test is therefore able to
      evaluate GH secretory dynamics through two major mechanisms, GHRH stimulation and
      SRIH inhibition in a single procedure, reducing the incidence of false negative
      GH response to Arg.

PMID- 1982091
TI  - Parasympathetic nervous system in patients with Graves' disease determined by R-R
      interval variations on electrocardiogram.
AB  - Little is known about an interrelationship between thyroid dysfunction and
      parasympathetic nervous system. R-R interval variations on electrocardiogram
      (ECG) have been considered to be reliable indicator reflecting abnormalities of
      parasympathetic nervous system. We have attempted to apply this technique in
      patients with hyperthyroidism. Studies were conducted in 60 healthy subjects and
      57 patients with Graves' disease. R-R interval variations were expressed as
      coefficient of variation on 100 heart rates at the time of resting (CVq) and deep
      respiration (CVd). A negative correlation between R-R interval variations (CVq,
      CVd) and ages was observed in healthy subjects. CVq was significantly lower in
      untreated Graves' disease than in antithyroid drug-treated Graves' disease and
      control subjects. A similar result also was obtained in CVd. Decreased CVq in
      untreated patients with Graves' disease was restored by administration of beta
      blockades, propranolol and metoprolol, but not by administration of alpha
      blockade, bunazosine. The present investigation suggests that there are
      hypofunctions in parasympathetic nervous system associated with beta (especially
      beta one) effects in patients with hyperthyroidism due to Graves' disease.

PMID- 1982092
TI  - Third International Berlin-Conference for Sexology. July 10-15, 1990. Abstracts.

PMID- 1982093
TI  - Comparative effects of pancuronium and vecuronium on rat diaphragm and isolated
      hepatocytes.

PMID- 1982094
TI  - Bioenergetic studies of bloodstream forms of Trypanosoma brucei: electrical and
      H+ gradients.

PMID- 1982095
TI  - Potential therapeutic exploitation of the pulmonary polyamine uptake system.

PMID- 1982096
TI  - Bioprecursor approach to drug targeting.

PMID- 1982097
TI  - Adaptations of glucose metabolism in white-fat adipocytes at weaning in the rat
      are concomitant with specific gene expression.

PMID- 1982098
TI  - Inhibition of the bloodstream/procyclic transformation in Trypanosoma brucei.

PMID- 1982099
TI  - Role of the pentose phosphate pathway in the provision of precursors for nucleic
      acid biosynthesis in bloodstream Trypanosoma brucei.

PMID- 1982100
TI  - Molecular forms of angiotensin-converting enzyme in brain microvessels.

PMID- 1982101
TI  - Activity and expression of hepatic mitochondrial 3-hydroxy-3-methylglutaryl-CoA
      synthase during the starved-to-fed transition.

PMID- 1982102
TI  - Identification of asialo GM1 as a binding structure for Escherichia coli
      colonization factor antigens.
AB  - We have examined the binding of colonization factor antigens, (CFAs) of
      enterotoxigenic Escherichia coli to gangliosides and asialo gangliosides by using
      immuno-thin layer chromatography. CFA/II and its subcomponents (CS1, CS2 and CS3)
      as well as the subcomponent CS4 of the CFA/IV complex bound to asialo ganglioside
      GM1.

PMID- 1982103
TI  - Specific detection of Escherichia coli and Shigella species using fragments of
      genes coding for beta-glucuronidase.
AB  - The occurrence of beta-glucuronidase activity, a main characteristic of
      Escherichia coli and the presence of the uid chromosomal region of E. coli,
      coding for this enzyme, were tested on representative members of enteric
      bacteria. DNA hybridization techniques using uid probes and amplification
      experiments of uidA gene by the polymerase chain reaction (PCR) confirmed the
      specificity of uid genes for E. coli and Shigella spp. (i.e., S. boydii, S.
      dysenteriae, S. flexneri and S. sonnei), independent of the beta-glucuronidase
      phenotype of bacterial strains. This specificity seemed to be conserved when
      studies were extended to a wide range of bacteria. It was not possible to
      distinguish E. coli from Shigella spp. The detection sensitivity using double
      stranded DNA radiolabeled probes was 3 x 10(4) bacteria and could be brought down
      to 8 bacteria by PCR. Thus, the uid genes appeared to be ideal candidates for DNA
      probes technology to detect E. coli-Shigella species.

PMID- 1982104
TI  - The detection of genetic variation in Leptospira interrogans serogroup
      ICTEROHAEMORRHAGIAE by ribosomal RNA gene restriction fragment patterns.
AB  - Deoxyribonucleic acid from Leptospira interrogans serogroup ICTEROHAEMORRHAGIAE
      reference strains together with clinical and animal isolates were cleaved with
      EcoRI, electrophoresed and transferred to nylon membranes. An Escherichia coli
      MRE 600, 16S + 23S ribosomal RNA template was used in the synthesis of a single
      strand biotin-labelled cDNA probe using a reverse transcriptase. Ribosomal RNA
      cistrons present in the DNA fragments of strains were located using the cDNA
      probe. Between 4 and 7 well defined ribosomal RNA restriction bands were detected
      for the leptospires studied that varied in size from 12.1 to 0.57 kb. The
      hybridisation patterns were distinctive and unique for the reference strains that
      allowed for their characterisation. Similar patterns were observed for I.
      budapest M 20, I. "icterohaemorrhagiae" Ictero I and the type strain, I.
      icterohaemorrhagiae RGA. Clinical isolates and a isolate from a rat were compared
      with reference strain DNA patterns and identified as being similar to I.
      copenhageni M 20, I. "icterohaemorrhagiae" Ictero I and I. icterohaemorrhagiae
      RGA. These results indicate that ribosomal DNA fingerprinting may be useful in
      the classification and molecular epidemiology of pathogenic leptospires.

PMID- 1982105
TI  - Identification and characterization of a GroEL homologue in Rhodobacter
      sphaeroides.
AB  - A protein closely related to the Escherichia coli GroEL protein has been isolated
      from Rhodobacter sphaeroides. Native and SDS-polyacrylamide gel electrophoresis
      of this protein have shown that it is present in the cell as a multimeric complex
      of Mr 670,000 which is composed of a monomer of Mr 58,000. Antisera raised
      against the Mr 58,000 polypeptide have been shown to cross-react with GroEL and
      the alpha subunit of the pea plastid chaperonin. The N-terminal amino acid
      sequence of the Mr 58,000 polypeptide is identical to that of GroEL at 15 of 19
      residues and is also closely related to the alpha subunit of the pea plastid
      chaperonin, though less so to the beta subunit.

PMID- 1982106
TI  - Heparin and secondary prevention of acute myocardial infarction.
AB  - Patients surviving acute myocardial infarction (AMI) may experience several
      clinical events (reinfarction, congestive heart failure, sudden death) still
      responsible for high mortality rates. AMI early complicated by residual angina,
      left ventricular dysfunction, or malignant arrhythmias has a worse prognosis.
      Secondary prevention of myocardial infarction and death has been the end point of
      many clinical trials in the past two decades. It is well known that beta blockers
      prevent sudden death if administered chronically after AMI. Meta-analysis of
      controlled randomized trials demonstrated a significant reduction in reinfarction
      and vascular death with long-term antiplatelet treatment. Oral anticoagulants
      prevent fatal and non-fatal reinfarction and show a trend towards lower mortality
      rates, though treated patients have a higher incidence of haemorrhagic events,
      particularly stroke. Early administration of heparin gave contradictory results
      on short-term prevention of myocardial infarction and death after AMI. Data on
      long-term heparin therapy point out a significant reduction in recurrent AMI and
      a trend towards a decrease in general mortality.

PMID- 1982107
TI  - Epidemiology and treatment of gastric Campylobacter pylori infection: more
      questions than answers.
AB  - Two-hundred and ten consecutive patients undergoing routine gastroscopy were
      additionally investigated for evidence of Campylobacter pylori (C.p.). 106
      patients were positive in one or more tests: 99.1% using a rapid urease detecting
      test (CLO-test), 80.2% histology, 78.3% cytology and 60% culture. We found no
      difference between the CLO-test results from biopsies taken from different parts
      of the stomach in individual patients. C.p. was found in 100% of patients with
      significant chronic antral gastritis, 67.7% with gastric ulcers, 65% with
      duodenal ulcers and in 12.1% of normal individuals. The C.p. infection was
      apparently eliminated in 50% of cases treated with bismuth subsalicylate (BSS)
      for four weeks. The combination of BSS with amoxicillin, tinidazole or an H2
      receptor antagonist offered no advantage over BSS alone. Treatment with BSS led
      to improvement in symptoms and histological findings including healing of ulcers
      in patients with or without persistent C.p. infection. The recurrence of C.p.
      infection after apparently successful treatment was, however, 75% in 4 weeks. In
      conclusion, C.p. infection correlates strongly with the presence of chronic
      gastritis, and significantly with gastric and duodenal ulceration. The best
      diagnostic approach is the combination of a rapid urease detecting test and
      histology. C.p. infection is of long duration and difficult to eliminate. The
      most effective treatment for C.p. infection remains BSS as single agent.

PMID- 1982108
TI  - Comparison of 150 mg nizatidine BID or 300 mg at bedtime, and 150 mg ranitidine
      BID in the treatment of gastric ulcer--an 8-week randomized, double-blind
      multicentre study.
AB  - One hundred and one active gastric ulcer patients concluded an 8-week,
      randomized, double-blind multicentre study, planned with the aim to compare the
      effectiveness of a new H2 blocker, nizatidine, with ranitidine. Thirty-three
      patients received 300 mg nizatidine at bedtime, 34,150 mg nizatidine b.i.d. and
      34,150 mg ranitidine b.i.d. The three groups were well matched for the common
      clinical parameters. After 4 weeks, healing rates were 51.5% (confidence
      intervals 95%: 34.1-68.9%), 61.8% (41.2-82.4%), 76.5% (51-102%), respectively. At
      this check point ranitidine showed a significantly better outcome than did 300 mg
      nizatidine at bedtime (p less than 0.05). After 8 weeks, healing rates were 81.8%
      (54.1-109.5%), 88.2% (58.7-117.7%) and 88.2% (58.7-117.7%); these differences
      were not statistically significant. Age, sex, ulcer symptoms, alcohol and
      cigarette consumption, concomitant treatments, ulcer size and site and length of
      ulcer history were all found not to influence ulcer healing. Pain relief and
      antacid consumption were comparable in the three treatment groups. No clinically
      significant unwanted effects were recorded throughout the study. Nizatidine can,
      in our opinion, be successfully used in the treatment of active gastric ulcer.

PMID- 1982109
TI  - Studies on four restriction fragment length polymorphisms of the type I collagen
      genes in two Italian populations.
AB  - Type I collagen, the most abundant of the collagen protein family, is encoded by
      two genes, COL1A1 and COL1A2. Two random population samples, one from central
      Italy and one from southern Italy, were studied for 1 restriction fragment length
      polymorphism (RFLP) of COL1A1 (RsaI) and 3 RFLPs of COL1A2 (EcoRI, RsaI and
      MspI). A considerable heterogeneity for COL1A1/RsaI was found not only between
      Italians and English but even among Italians. The potential usefulness of these
      RFLPs and haplotypes as anthropogenetic markers, particularly in distinguishing
      Caucasoids from Negroids, has been discussed.

PMID- 1982110
TI  - Treatment of traumatic dental injuries. Shift in strategy.
AB  - A more conservative approach to the treatment of traumatic dental injuries has
      been made possible by knowledge concerning the pathogenesis of external root
      resorption, increased knowledge about wound healing processes in the pulp and
      periodontium, as well as by advances in restorative dentistry (reattachment of
      crown fragments with a dentin bonding system, the use of adhesive bridges, and
      advances in autotransplantation and implantation). However, a rethinking by the
      public, clinicians, and third-party payers is necessary for these procedures to
      gain wider acceptance. The present article describes the state of the art of
      treating dental trauma in the hope that these advances can become an accepted
      part of the dental trauma armamentarium and not merely scientific curiosities.

PMID- 1982111
TI  - Effect of temperature on alpha 2- and alpha 1-adrenoceptor-mediated responses in
      the pithed rat and in the rat vena cava.
AB  - 1. The influence of body temperature on the alpha 1- and alpha 2-adrenoceptor
      mediated pressor responses has been investigated in the pithed rat. 2. The
      pressor responses to noradrenaline, to the full alpha 1-adrenoceptor agonists
      phenylephrine and cirazoline and to tyramine were not influenced by lowering the
      temperature from 36-37 degrees C to 27-29 degrees C. In contrast, the dose
      response curves for the pressor effects of the partial alpha 1-adrenoceptor
      agonist ST 587 and of the alpha 2-adrenoceptor agonist B-HT 920 (2-amino-6-allyl
      5,6,7,8-tetrahydro-4H-thiazolo-[4,5-d]-azepine), B-HT 933 (2-amino-6-ethyl
      5,6,7,8-tetrahydro-4H-[4,5-d]azepine), clonidine, moxonidine and M-7 (2
      dimethylamino-5,6-dihydroxy-1,2,3,4-tetrahydronaphthalene hydrobromide) were
      markedly depressed (without change in the ED50 values), when the body temperature
      was lowered from 36-37 degrees C to 27-29 degrees C. 3. After i.v. administration
      of yohimbine, there was a rightward shift of the dose-response curve for B-HT
      920, and the degree of this shift was the same at all temperatures investigated.
      4. In the rat vena cava preincubated with [3H]-noradrenaline, the B-HT 920
      induced alpha 2-adrenoceptor-mediated inhibition of electrically evoked tritium
      overflow was also reduced at lower temperature. 5. These results are compatible
      with the suggestion that cooling decreases the alpha 2-adrenoceptor-mediated pre-
      and postsynaptic responses in the rat vena cava and pithed rat respectively,
      leaving the pressor effect induced by full, but not partial alpha 1-adrenoceptor
      agonists in the pithed rat unaffected. 6. These differences may partly be related
      to differences in receptor reserve for alpha 1- and alpha 2-adrenoceptors in the
      pithed rat preparation.

PMID- 1982112
TI  - Modulation of gastric acid secretion by peripheral presynaptic alpha 2
      adrenoceptors at both sympathetic and parasympathetic pathways.
AB  - 1. The effects of the alpha 2-adrenoceptor agonist detomidine, and the
      antagonists idazoxan and CH-38083 were examined on gastric acid secretion from
      non-vagotomized and vagotomized stomach lumen-perfused rats. The effects of
      detomidine on acid secretion from isolated guinea-pig gastric fundus were also
      evaluated. 2. In both non-vagotomized and vagotomized rats i.p. administration of
      detomidine significantly increased acid secretion, whereas i.c.v. detomidine was
      without effect. The stimulant action of i.p. detomidine was antagonized by both
      i.p. idazoxan and CH-38083 as well as by pretreatment with reserpine. 3. In
      vagotomized and reserpinized rats whose acid secretion was increased by
      electrical stimulation of the left vagus nerve, i.p. injection of detomidine
      caused inhibitory effects on acid secretion which were fully antagonized by both
      i.p. idazoxan and CH-38083. 4. Both idazoxan and CH-38083 caused a significant
      increase in acid secretion induced by vagal stimulation. At higher doses the two
      antagonists displayed a potentiating effect on vagally induced acid secretion
      only when they were associated to i.v. infusion of prazosin and propranolol. 5.
      Detomidine was without effect on acid secretion from isolated guinea-pig gastric
      fundus, whereas histamine or bethanechol caused a marked and dose-dependent
      stimulant action. 6. Overall, these results provide evidence that peripheral
      presynaptic alpha 2-adrenoceptors modulate both adrenergic inhibitory and
      cholinergic excitatory influences on rat gastric acid secretion.

PMID- 1982113
TI  - Mechanisms of positional signalling in the developing eye of Drosophila studied
      by ectopic expression of sevenless and rough.
AB  - In the developing eye of Drosophila cell fate is controlled by a cascade of
      inductive interactions. Little is known about how the specificity of positional
      signalling is achieved such that directly adjacent progenitor cells reproducibly
      choose distinct developmental pathways. The determination of the R7 photoreceptor
      in each ommatidium depends on the presence of the sevenless protein which acts as
      a receptor for positional information on the R7 precursor. The rough gene encodes
      a homeodomain protein that plays an instructive role in the determination of the
      R3 and R4 photoreceptor cells. The use of ectopic expression of sevenless and
      rough has provided insight into the mechanisms of positional signalling and the
      normal function of rough. Ubiquitous expression of sevenless does not alter cell
      fate suggesting that the inducing signal is both spatially and temporally
      controlled. Conversely, ectopic expression of rough in the R7 precursor causes a
      transformation of R7 cells into R1-6 type cells. This indicates that rough acts,
      similar to other homeobox genes, as a selector gene that determines the fate of
      single cells.

PMID- 1982114
TI  - EMBO workshop: dynamics of cellular motor proteins.

PMID- 1982115
TI  - Abstracts of the EMBO Workshop on Dynamics of Cellular Motor Proteins. Cambridge,
      UK, 8-13 September, 1990.

PMID- 1982116
TI  - Cardiovascular responses elicited by chemical stimulation of the rostral
      ventrolateral medulla in conscious, unrestrained rats.
AB  - The cardiovascular effects of microinjection of L-glutamic acid into the rostral
      ventrolateral medulla have been investigated in anaesthetized and in conscious,
      unrestrained rats. In conscious rats L-glutamic acid (0.36, 1.2 and 2.4 nmol)
      produced significant increases in blood pressure, generally accompanied by a
      bradycardia. A lower dose of L-glutamic acid (0.12 nmol) had no effect on blood
      pressure or heart rate. The cardiovascular responses elicited by L-glutamic acid
      (2.4 nmol) were completely abolished by intravenous infusion of the ganglion
      blocker, pentolinium. However, in urethane-anaesthetized rats, the pressor
      response (+27 +/- 2/+21 +/- 2 mmHg) to microinjection of L-glutamic acid (2.4
      nmol) was markedly less than that seen in conscious rats (+64 +/- 6/+47 +/- 3
      mmHg) and there was a tachycardia (+21 +/- 2 beats/min) rather than a
      bradycardia. These results corroborate previous studies, carried out in
      anaesthetized animals, indicating that stimulation of the rostral ventrolateral
      medulla provides direct and/or indirect excitatory drive to the preganglionic
      sympathetic neurons of the spinal cord to increase blood pressure, but
      demonstrate a marked difference in sensitivity in conscious vs urethane
      anaesthetized animals.

PMID- 1982117
TI  - Central effects of an alpha 2-adrenergic antagonist on fetal lambs: a possible
      mechanism for hypoxic apnea.
AB  - In 12 chronically-prepared fetal lambs at 128-135 days gestation, a specific
      alpha 2-antagonist, L-657,743 (Merck) was infused into a lateral cerebral
      ventricle for periods of up to 24 h. Control infusions of artificial CSF had no
      effect. L-657,743 at a dose rate sufficient to block the actions of injected
      clonidine did not affect breathing incidence or episode duration, electrocortical
      activity, heart rate, arterial pressure or blood gases during normoxic
      conditions. However, 5 out of 6 preparations receiving L-657,743 while hypoxic
      continued to breathe during hypoxia instead of becoming apneic as normal. The
      central effects of alpha 2-adrenergic blockade appear to be specific to hypoxia.
      It is concluded that fetal hypoxic apnea may be mediated by inhibitory alpha 2
      adrenergic receptors which can be blocked by the antagonist L-657,743.

PMID- 1982118
TI  - Fine structure of tyrosine hydroxylase-like immunoreactive neurons and terminals
      of the hypothalamic arcuate nucleus and median eminence in young and aged rats.
AB  - Tyrosine hydroxylase (TH)-like immunoreactive neurons, fibers, and terminals in
      the hypothalamic arcuate nucleus and median eminence of young (8 weeks old) and
      aged (24 months old) rats were investigated at light and electron microscopic
      levels by means of the peroxidase anti-peroxidase (PAP) method. In the arcuate
      nucleus, TH-like immunoreactive neuronal perikarya of young animals contained
      well-developed cell organelles such as rough-surfaced endoplasmic reticulum
      (rER), mitochondria, Golgi apparatus, polysomes, as well as dense granules.
      Immunoreactive neuronal elements appeared as both presynaptic and postsynaptic
      elements. In aged rats, TH-like immunoreactive neuronal perikarya as well as non
      immunoreactive ones were found to include many lysosomes or inclusions, and many
      neuronal elements with degradative changes were observed. In the external layer
      of the median eminence of young animals, many immunoreactive nerve endings were
      found around the pericapillary spaces of portal vessels and often terminated
      adjacent to the basement membranes of the pericapillary spaces. Immunoreactive
      fibers having close contact with non-immunoreactive fibers were also observed. In
      aged animals, degradative changes such as axons with swollen and watery
      appearance and myelin figures were observed in the neuronal elements, although
      many immunoreactive nerve endings were seen around the pericapillary spaces.

PMID- 1982119
TI  - Hemolysis following correction of ventricular septal defect.
AB  - Hemolysis following repair of a ventricular septal defect (VSD) is an unusual
      complication. Three cases of patients who had simple VSD are described here.
      After repair of the VSD, the postoperative course was complicated by the
      intravascular hemolysis induced by the interaction between the red blood cells
      and the double velour Dacron patch. Thus the patients' hemodynamic status
      deteriorated. The first 2 patients had a course of hemoglobinuria,
      hyperamylasemia, hyperglycemia, malignant hypertension, hepatospenomegaly, acute
      renal failure and hypertensive encephalopathy. One patient, who did not undergo
      reoperation, died due to multiple organ failure; the other one, who underwent
      operation revision in order to arrest the hemolysis, died of sepsis. Early
      reoperation was performed in the remaining patient to replace the double velour
      Dacron patch with a pericardium-covered knitted Dacron patch, and he survived.
      Hemolysis ceased in both patients who had the double velour Dacron patch replaced
      with a pericardium-covered patch. A review of the literature failed to show
      previous reports concerned with hemolysis associated with repair of a simple VSD.
      We now report what we believe to be the first cases in the literature with this
      unique clinical course following hemolysis.

PMID- 1982120
TI  - Coarctation of aorta coexisting with pheochromocytoma: report of a case.
AB  - A patient was admitted for a study of his hypertension because coarctation of the
      aorta (COA) was suspected. His history also provided clues of pheochromocytoma. A
      computed tomography (CT) scan revealed a right-side supraadrenal tumor. A study
      of urine catecholamine showed a strong positive result. Cardiac catheterization
      revealed that the patient had a postductal COA and a supraadrenal tumor. Surgery
      and pathology confirmed that the patient had pheochromocytoma.

PMID- 1982121
TI  - Leiomyoma of the bronchus: report of a case successfully treated by Nd-YAG laser
      via fiberoptic bronchoscope.
AB  - A 42-year-old woman presented with chronic cough and dyspnea. A leiomyoma of the
      right middle lobe of the bronchus was diagnosed by bronchoscopic biopsy and
      treated successfully by neodymium-yttrium aluminum garnet laser, via fiberoptic
      bronchoscope. The presentations of bronchial leiomyoma are mainly due to partial
      or complete occlusion of the involved bronchus. Symptoms are mainly cough,
      wheeze, chest pain and fever, as a result of atelectasis, consolidation, collapse
      or bronchiectasis. The management of this benign tumor of the lung is discussed,
      and the importance of early diagnosis and conservative therapy are emphasized.

PMID- 1982122
TI  - [Non-Hodgkin's lymphoma in adults: a clinico-pathologic study of 169 cases].
AB  - From 1983 to 1988, non-Hodgkin's lymphoma was diagnosed in 169 patients ranging
      from 19 to 89 years of age (mean 49). They were investigated using both
      unifactorial and multivariate regression (Cox model) analyses to determine the
      relationship of survival rate and prognostic factors including age, sex,
      histology, B symptom and clinical stage. All cases were histologically classified
      according to the criteria of the working formulation and were staged according to
      the Ann Arbor classification. Non-Hodgkin's lymphoma occurred roughly 9 times as
      frequently as Hodgkin's disease. The lymph nodes of the neck and inguinal regions
      were noted to be the most common sites of involvement. However, extranodal
      lymphomas originated most frequently from the stomach. For the patients with non
      Hodgkin's lymphoma, the proportions of low grade, intermediate grade, and high
      grade were 10.7%, 59.1% and 20.7%, respectively. The remaining 9.5% of cases were
      unclassified (7.7%) and true histiocytic (1.8%). The most common subtype was
      diffuse large cell (33.7%). Lymphoblastic lymphoma was found to have a
      predilection for young male adults. Follicular lymphomas occurred mainly in mid
      adult life. The patients with high grade lymphoma almost always presented the
      advanced stage. The median survival time (MST) of our series was 20 months, the 3
      year survival rate was 43.3% and the 5-year survival rate was 30.40%. Statistical
      studies of both unifactorial (p less than 0.01) and multivariate regression (p
      less than 0.05) analyses showed that patients with an age greater than 60 years
      old, having B symptom, clinically advanced stage, or both histologically
      intermediate and high grade experienced a much poorer prognosis.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1982123
TI  - [Epidemiologic study of pathogens causing nosocomial infections].
AB  - Nosocomial infection is a global problem. It significantly adds to the expected
      duration of hospitalization resulting with an increased economic burden and
      represents a leading cause of death. The characteristics of nosocomial infection
      vary from country to country and also changes with time. In order to understand
      the pathogens causing nosocomial infection in the large teaching hospital in
      Taiwan, we collected and analysed the surveillence data of nosocomial infection
      at the National Taiwan University Hospital from 1981 to 1989. We found that the
      nosocomial infection rate had been around 4-5% annually since 1981 till 1989. As
      ranked according to the site of infection, surgical wound infections were the
      most common, followed by the urinary tract, respiratory tract, and blood stream
      infections. However, the incidence of surgical wound infections had decreased
      gradually. About one third of nosocomial infections were caused by multiple
      microorganisms. The most frequently isolated pathogen has changed from
      Escherichia coli in early years to Pseudomonas aeruginosa in the most recent
      years. Gram-negative aerobic bacteria has been the major pathogens resulting in
      nosocomial infections for the past 9 years, accounting for 55-66%. In contrast,
      fungi have increased rapidly from 1.8% of total isolates in 1981 to 7.7% in 1989.
      Gram-positive cocci have also increased in recent years. The leading pathogen by
      infection site was P. aeruginosa in surgical wound infections, E. coli in urinary
      tract infections, and P. aeruginosa in respiratory tract infections. In earlier
      years E. coli was the major isolate in bacteremic cases, but glucose non
      fermenters, including P. aeruginosa, Acinetobacter calcoaceticus and others, plus
      Enterobacter species-emerged as the major pathogens of recent years.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1982124
TI  - [Blood viscosity and blood factors in non-embolic cerebral infarction].
AB  - We compared blood viscosity at a high and a low shear rate, hematocrit, as well
      as levels of fibrinogen, cholesterol, triglyceride and high density lipoprotein
      cholesterol between 42 patients with nonembolic cerebral infarction and 39 normal
      subjects. Blood viscosity, levels of fibrinogen, cholesterol and triglyceride
      were significantly higher, and high density lipoprotein-cholesterol levels were
      significantly lower, in patients than in normal persons. Blood viscosity had a
      positive correlation with hematocrit and fibrinogen, and a negative correlation
      with high density lipoprotein-cholesterol, but no correlation with cholesterol
      and triglyceride.

PMID- 1982125
TI  - Detection of human papillomavirus DNA in human cervical lesions by tissue in situ
      nucleic acid hybridization.
AB  - Cervical cancer is one of the most common female cancers in Taiwan. Certain types
      of human papillomavirus (HPV) are frequently detected in the epithelial
      precancerous and cancerous lesions of the cervix. By the use of tissue in situ
      hybridization, we investigated the relationship of various types of HPV (group I,
      HPV-6 & 11, group II, HPV-16 & 18, group III, HPV-31, 33 & 35) with cervical
      condyloma, carcinoma as well as precancerous lesions. Group I HPV DNAs were
      mainly found in cervical condylomatous lesions (2/2) of the cervix and cervical
      intraepithelial neoplasia I (CIN I) (2/4), but were only occasionally found in
      CIN II (1/4), CIN III (1/9) or non-keratinized squamous cell carcinoma (1/15).
      HPV DNAs of groups II and III were mainly detected in lesions of CIN III (5/9)
      and invasive squamous cell carcinoma (large cell, keratinized type: 4/7; large
      cell, non-keratinized type: 11/15). HPV DNA sequences were invariably detectable
      only in the cell nuclei of condyloma or dysplastic epithelium or invasive
      carcinoma. However, they could not only be detected in the upper layer dysplastic
      cells and koilocytes but also in the well and poorly differentiated cervical
      cancer cells. The distribution of HPV DNA positive cells in the carcinomas fell
      into four different patterns: (1) upper zone and non-invasive regions of the
      carcinoma (11/22, 50%), (2) basal zone and invasive regions (2/22, 9%), (3)
      randomly scattered (7/22, 32%), and (4) extensively distributed over the whole
      tumor lesions (2/22, 9%). Thus, our results are consistent with a strong
      correlation between the presence of HPV-16, 18, 31, 33 and 35 and malignant
      conversion of cervical epithelial cells.

PMID- 1982126
TI  - Interactions between cloned gingival or periodontal ligament cells and oral
      epithelial cells in vitro.
AB  - Interactions between epithelial cells and fibroblast clones were examined to
      determine whether various fibroblasts clones derived from gingival or periodontal
      tissues responded differently to oral epithelial cells. We provide evidence that
      epithelial root sheath (ERS) cells enhanced collagen type I (CI) expression in
      most periodontal clones, whereas ERS cells variably influenced CI expression of
      gingival fibroblast clones. Modulation of collagen type III (CIII) expression in
      both gingival and periodontal clones by ERS cells was less in magnitude and
      mostly suppressive in gingival clones. Fibronectin (Fn) expression in many
      gingival and periodontal clones was decreased in cells associated with ERS cells.
      On the other hand, the influence of gingival epithelial cells on fibroblast
      clones tended to be inhibitory, especially in periodontal clones. Thus, gingival
      epithelial (GE) cells suppressed the expression of collagen types I and III and
      Fn in most periodontal clones. Except for suppression of Fn expression, GE cells
      had less influence on CI and CIII expression in gingival clones. The modulations
      of fibroblast extracellular matrix components by ERS and GE have profound
      implications for the regulation of the development, repair and regeneration of
      the periodontal tissues.

PMID- 1982127
TI  - Polymorphic locus in the 5'-flanking region of human insulin gene and non-insulin
      dependent diabetes mellitus.
AB  - The etiology of non-insulin-dependent diabetes mellitus (NIDDM) is still unclear,
      but appears to involve some genetic factors. There have been disputes over the
      association between DNA sequences flanking the insulin gene and NIDDM. In order
      to characterize insulin gene polymorphism in the Chinese population and elucidate
      its association with NIDDM, 100 unrelated Chinese subjects living in Taiwan were
      observed for polymorphism of this hypervariable region. Most of them were
      descendants of immigrants from the southern part of mainland China. Among them,
      52 were nondiabetic controls, and 48 were subjects with NIDDM. Insulin gene
      polymorphism was classified into classes 1, 2 and 3 alleles according to Bell et
      al. Neither the class 2 allele nor the genotype for the homozygous class 3 allele
      was not observed in this study. The allelic frequencies of class 1 and 3 genes
      were 97% and 3% in the nondiabetic subjects, and 99% and 1% in the NIDDM group,
      respectively. The frequencies of genotypes 1/1 and 1/3 were 94% and 6% in
      nondiabetics and 98% and 2% in the NIDDM group, respectively. No significant
      association was found between insulin gene polymorphism and NIDDM. It is
      concluded that DNA marker flanking the insulin gene may not be associated with
      the development of NIDDM in Chinese subjects.

PMID- 1982128
TI  - Islet cell and other organ-specific autoantibodies in Chinese children with
      insulin-dependent diabetes mellitus.
AB  - Islet cell autoantibodies (ICA) and other organ-specific autoantibodies were
      detected in 27 Chinese children with insulin-dependent diabetes mellitus (IDDM).
      The frequency of ICA within the first year of diagnosis was 67%, and it declined
      as the duration of the disease increased. The frequencies of thyroid microsomal
      autoantibodies and gastric parietal cell autoantibodies were 26% and 11%,
      respectively. None of the patients had adrenal autoantibodies. These results are
      comparable to those reported in Caucasian patients. Similar frequencies of islet
      cell autoantibodies and other organ-specific autoantibodies in children with IDDM
      between Chinese and Caucasians suggest that the autoimmune process may play an
      important role in the pathogenesis of Chinese children with IDDM.

PMID- 1982129
TI  - Relation between body composition, anthropometry, and glucose tolerance.
AB  - Based upon the results of a 75 g oral glucose tolerance test, 305 subjects (157
      men and 148 women), who were admitted to the National Cheng Kung University
      Hospital for health check-up, were divided into diabetic (n = 47, 25 men and 22
      women), impaired glucose tolerance (IGT) (n = 53, 27 men and 26 women) and normal
      (n = 205, 105 men an 100 women) groups. All diabetics were of non-insulin
      dependent diabetics. Body composition and anthropometries including body mass
      index (BMI), thickness of triceps skinfold (TSF), arm muscle circumference (AMC),
      and blood pressure were compared among these three groups. Body composition
      (percentage of fat, lean mass and total body water) was significantly correlated
      to BMI, TSF, AMC, blood pressure, blood glucose, hemoglobin Alc (HbAlc) and
      cholesterol. BMI was significantly correlated to blood pressure, blood glucose,
      HbAlc, triglyceride and serum glutamic pyruvic transaminase (SGPT) levels. TSF
      and AMC were not correlated to blood pressure, blood glucose, HbAlc or blood
      lipids. However, in defining adiposity, TSF seems more sensitive than BMI. The
      data of the IGT group did not show a significant difference from those of the
      normal group except for a higher systolic pressure and a 2-hour plasma glucose
      level after a 75 g oral glucose loading. The diabetic group showed significantly
      higher BMI, systolic pressure, triglyceride, and SGPT levels than both the IGT
      and normal groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1982130
TI  - Opsonizing effect of normal cerebrospinal fluid on Staphylococcus aureus.
AB  - The opsonizing effect of normal cerebrospinal fluid (CSF) on Staphylococcus
      aureus has been demonstrated through phagocytic assay. Radiolabelled S. aureus
      was opsonized using various CSF preparations and then ingested by neutrophils.
      Uptake of S. aureus by neutrophils was 31 +/- 12% for untreated CSF, 28 +/- 14%
      for ethylene-glycol-bis(beta-aminoethyl ether) -N,N-tetraacetic acid(EGTA)
      chelation, 18 +/- 5% for heat-treated (50 degrees C), 14 +/- 8% for heat
      inactivated (56 degrees C), 11 +/- 6% for S. aureus-absorbed, and 5 +/- 4% for
      heat-inactivated and S. aureus-absorbed, respectively. Indirect
      immunofluorescence antibody assay revealed that IgG was the class of
      immunoglobulins involved in the opsonic activity of CSF, and complement 3 (C3)
      deposition was weakly detected in S. aureus. These results suggest that both heat
      labile (complement) and heat-stable (antibody) factors are crucial for the
      opsonization of S. aureus by normal CSF. We conclude that activation of the
      complement by S. aureus in normal CSF is through an alternative pathway and is
      enhanced by the presence of a specific antibody (IgG).

PMID- 1982131
TI  - In vitro fragmentation of renal calculi of different components using
      electrohydraulic shock wave, ultrasound, and pulsed dye laser as energy sources:
      a preliminary report.
AB  - Renal calculi of five different components (whewellite, weddellite,
      struvite/apatite, uric acid, and cystine) received in vitro fragmentation by
      three energy sources currently available in endourology: electrohydraulic shock
      waves, ultrasound, and pulsed dye laser. Weddellite, struvite/apatite, and uric
      acid calculi were sufficiently disintegrated by all three energy sources.
      Whewellite stone was best treated by electrohydraulic shock waves, while cystine
      calculus was penetrated only by ultrasound. The ultrasonic lithotriptor was
      safer, but weaker and more cumbersome. The electrohydraulic lithotriptor was more
      powerful, but violent. The laser lithotriptor was both safe and powerful.
      However, there was not a single energy source that sufficiently disintegrated all
      five kinds of calculi mentioned.

PMID- 1982132
TI  - Surgical treatment of the ruptured bladder: 22 years reviewed.
AB  - During the 22-year interval from 1964 to 1985, 36 patients with bladder injuries
      were treated at the Kaohsiung Medical College Hospital. Thirty-two cases were
      male (89%) and 4 cases were female (11%), the sex ratio of patients was 8 to 1,
      respectively. The average patient age was 33 years and 75% were less than 40
      years of age. Hematuria was present in all of the patients and it was microscopic
      in 25%. Traffic accidents accounted for 55% of the injuries; penetrating trauma
      was responsible in only 6% of the patients. Of the 36 bladder trauma cases, 11
      (30.5%) had intraperitoneal injury, 24 (66.7%) had extraperitoneal injury and 1
      (2.8%) had intraperitoneal and extraperitoneal injury. Of the 28 cases with
      pelvic fracture and bladder trauma in this study, 18 (60%) had extraperitoneal
      rupture, and 9 (30%) had intraperitoneal rupture. The position of intraperitoneal
      rupture was mostly at the posterior wall and dome, whereas that of the
      extraperitoneal rupture was partly located at the anterior wall and the bladder
      neck. Bladder rupture was treated by operative repair of the defect, bladder
      drainage by suprapubic cystostomy and/or urethral catheter and drainage of the
      perivesical space. The mortality rate with the ruptured bladder was 17%. Multiple
      injuries associated with the ruptured bladder and postoperative complications
      especially septic shock, were the main causes of mortality.

PMID- 1982133
TI  - Evaluation of vasculogenic impotence using dynamic penile washout test.
AB  - Two control volunteers and 8 impotent patients entered this study for evaluation
      of arterial function and venous competence of the corpus cavernosum. The skin and
      corporeal xenon-133 (Xe-133) penile washout tests were conducted on each person
      before and 5 and 60 minutes after an intracavernous injection of prostaglandin
      E1. The half-time clearance (T 1/2) and blood flow (Q) were used for evaluation.
      The parameters of the skin washout test obtained from impotent patients changed
      from T 1/2 = 14.3 +/- 6.2 minutes, Q = 3.75 +/- 2.56 ml/100g tissue/minute
      preinjection to T 1/2 = 5.23 +/- 1.78, Q = 9.96 +/- 2.69 at 5 minutes post
      injection and T 1/2 = 3.89 +/- 0.86, Q = 12.9 +/- 3.0 at 60 minutes post
      injection, p less than 0.01; while the corporeal washout test changed from T 1/2
      = 84.6 +/- 107.1 minutes, Q = 2.91 +/- 3.17 ml/100g tissue/minute to T 1/2 = 41.2
      +/- 99.6, Q = 10.6 +/- 9.7 and T 1/2 = 13.9 +/- 16.2, Q = 7.78 +/- 6.35, p less
      than 0.05, respectively. The flow ratio (post-injection/pre-injection) was 1.01
      6.04 at 5 minutes and 1.39-8.01 at 60 minutes later in the skin washout test, and
      1.07-72.2 at 5 minutes and 0.60-45.7 at 60 minutes in the corporeal washout test.
      However, the individual variations were considerable. This study suggests that
      the Xe-133 penile washout test after an intracavernous injection may help in
      demonstrating the hemodynamics of the cavernosal arteries and dorsal arteries,
      and in evaluating the severity of penile vascular impairment. Moreover, the flow
      ratio may reflect vascular compliance; the higher the ratio, the better the
      compliance.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1982134
TI  - The atrioventricular conduction axis of hearts with isolated ventricular septal
      defects.
AB  - We studied the surgical anatomy of 14 hearts with isolated ventricular septal
      defects and the precise relationship of the atrioventricular conduction axis to
      their rims. Ten of these hearts were investigated by serial sectioning of their
      atrioventricular conduction systems. All defects were divided into perimembranous
      or muscular types as previously suggested by Soto et al. The distinguishing
      feature of the perimembranous defect was that the central fibrous body formed
      part of its rim, this fact indicated that the conduction tissue was always to the
      right of the surgeon's hand when the defect was approached through the right
      atrium. The precise relationship of the ventricular conduction tissues varied
      depending upon whether the perimembranous defect extended into the inlet,
      trabecular or outlet components of the muscular septum. The nonbranching bundle
      was closest to the septal rim in the inlet and trabecular defects, frequently
      being buried in a remnant of the interventricular membranous septum. However, in
      these defects the nonbranching and branching bundles were also found in other
      specimens remote from the septal crest, yet were carried on the left ventricular
      aspect of the septum. In perimembranous inlet defects, the penetrating bundle
      detoured deep into the central fibrous body. In perimembranous outlet defects,
      the conduction tissues were remote from the septal crest. In contrast to these
      findings, the conduction tissues were away from the edges of the defects in
      trabecular and outlet muscular defects. In conclusion, in the perimembranous
      inlet defect, the placement of the sutures on the annulus of tricuspid valve
      should be avoided in view of its abnormal long penetrating bundle.

PMID- 1982135
TI  - Effects of chronic administration of perfluorooctanoic acid on fatty acid
      metabolism in rat liver: relationship among stearoyl-coenzyme A desaturase, 1
      acylglycerophosphocholine acyltransferase, and acyl composition of microsomal
      phosphatidylcholine.
AB  - Male and female rats were fed on a diet containing 0.01% (w/w) perfluorooctanoic
      acid (PFOA) for 2, 22, or 26 weeks and effect of PFOA on activities of microsomal
      1-acylglycerophosphocholine acyltransferase, microsomal stearoyl-coenzyme A (CoA)
      desaturase, peroxisomal beta-oxidation and on acyl composition of microsomal
      phosphatidylcholine in liver were studied. The treatment of male rats with PFOA
      for 2 weeks caused increases in the activities of stearoyl-CoA desaturase, 1
      acylglycerophosphocholine acyltransferase, and peroxisomal beta-oxidation. The
      elevated activities of microsomal 1-acylglycerophosphocholine acyltransferase and
      peroxisomal beta-oxidation were unchanging throughout the long-term treatment.
      The induced activity of microsomal 1-acylglycerophosphocholine acyltransferase
      was found to be highly correlated with the induced activity of peroxisomal beta
      oxidation. In contrast to these two enzymes, the increased activity of stearoyl
      CoA desaturase by the short-term treatment of rats with PFOA did not last for 26
      weeks, although the activity in rats treated for the long-term was higher than
      that of age-matched controls. The treatment of male rats with PFOA caused great
      alterations in the acyl composition of microsomal phosphatidylcholine. The high
      correlation seen between proportion of 18:1 in the C-2 position of
      phosphatidylcholine and activities of both stearoyl-CoA desaturase and 1
      acylglycerophosphocholine acyltransferase suggest that these two enzymes
      participate actively in the regulation of acyl composition of phosphatidylcholine
      in rat liver. The present results show that hepatic responses to PFOA remain
      consistent throughout the period of the administration, but the elevated
      activities of the hepatic enzymes and the altered acyl composition of microsomal
      phosphatidylcholine returned to control levels within 4 weeks after PFOA was
      withdrawn from the diet. Even after the chronic administration of PFOA, these
      parameters of female rats responded only slightly to the challenges by the
      chemical, which indicates a marked sex-related difference being still apparent in
      the response of rat liver to PFOA.

PMID- 1982136
TI  - The coating and the encapsulation of an interactive powder mixture and its
      application to sustained release preparations.
AB  - Fine cohesive isoprenaline HCl particles adhered to the surface of coarser potato
      starch particles to form interactive mixtures. These were coated with magnesium
      stearate by dry mixing. To check if there was a lowering of homogeneity in the
      latter stage, the degree of mixing was investigated before and after adding
      magnesium stearate. The surface appearance of magnesium stearate-coated
      interactive mixtures became smoother as mixing time increased or the temperature
      of the powder bed during mixing was raised. Ultimately, the magnesium stearate
      encapsulated the particles of interactive mixture. The coated interactive
      mixtures improved sustained release of isoprenaline HCl over the starch mixtures
      alone, the effect depending on the density of the magnesium stearate. Only in
      encapsulated mixtures was the release rate of drug decreased as the amount of
      magnesium stearate increased. The release of isoprenaline HCl from the
      interactive mixtures followed first-order kinetics. A linear relationship existed
      between the first-order rate constant and the reciprocal thickness of the
      magnesium stearate film, indicating a diffusion-controlled system with the film
      having some pores.

PMID- 1982137
TI  - Kinetics of the intestinal uptake of zinc acexamate in normal and zinc-depleted
      rats.
AB  - The uptake of zinc as acexamic acid salt in the small intestine of the
      anaesthetized rat was shown to be a two-phase process in normal animals. The
      first phase is rapid mucosal binding which satisfies the Freundlich isotherm
      equation and which involves about 30 per cent of the initially perfused zinc. The
      second phase was characterized as an apparent absorption step which obeys
      Michaelis-Menten and first-order combined kinetics, with the following
      parameters: Vm = 6.51 mg h-1; Km = 2.96 mg; ka = 0.306 h-1. In largely non
      saturated conditions, an apparent global rate constant of about 2.50 h-1 was
      calculated. No significant interference due to endogenous zinc excretion into the
      small intestine was observed during the absorption period. In zinc-deficient
      animals, the two phases were not so well characterized. Binding was non-linear
      and apparent absorption efficiency was much greater at high zinc concentrations,
      so no evidence of saturable kinetics was found, thus confirming the hypothesis of
      a homeostatic zinc regulation mechanism.

PMID- 1982138
TI  - Alpha 2-adrenoceptor-mediated inhibitory and excitatory effects of detomidine on
      rat gastric acid secretion.
AB  - The effects of the selective alpha 2-adrenoceptor agonist detomidine on gastric
      acid secretion from pylorus-ligated and stomach-perfused rats have been
      investigated. In pylorus-ligated rats i.p. injection of detomidine markedly
      inhibited acid secretion, this effect being prevented by yohimbine or idazoxan.
      Under the same conditions, idazoxan significantly increased secretion in a dose
      independent fashion. In non-vagotomized and vagotomized stomach-perfused rats
      i.p. detomidine stimulated acid secretion: this excitatory effect was antagonized
      by idazoxan. The present results suggest that both inhibitory and excitatory
      gastric secretory effects of detomidine are mediated by alpha 2-adrenoceptors on
      cholinergic and adrenergic nerves, respectively. The stimulant activity of
      idazoxan on gastric secretion from pylorus-ligated rats may be interpreted in
      terms of increased excitatory vagal tone following the blockade of inhibitory
      alpha 2-adrenoceptors.

PMID- 1982139
TI  - Comparison of the antisecretory effects of loperamide and loperamide oxide in the
      jejunum and the colon of rats in-vivo.
AB  - The antidiarrhoeal effect of loperamide is caused by its antimotility and
      antisecretory properties. In-vivo experiments in the rat jejunum and colon have
      been performed to compare the antisecretory effect of loperamide with the effect
      of its prodrug, loperamide oxide. Both loperamide and loperamide oxide
      administered intraluminally, equally and dose dependently (2 to 250 micrograms mL
      1) reduced PGE2-induced net fluid secretion (32 ng min-1 i.a.) in the jejunum and
      colon. The antisecretory effect of both drugs is blocked by naloxone (1 mg kg-1
      s.c.). It is concluded that loperamide oxide administered intraluminally is
      reduced to loperamide and has the same antisecretory potency as loperamide in
      jejunum and colon. The effect appears to be mediated via opiate receptors. The
      observation that loperamide cannot be detected in the colonic lumen two h after
      oral administration suggests that the drug is delivered from the blood stream to
      the site of action after absorption in the small intestine.

PMID- 1982140
TI  - Differential influence of laboratory anaesthetic regimens upon renal and
      hepatosplanchnic haemodynamics in the rat.
AB  - Renal blood flow in rats anaesthetized with the combination
      alphaxolone/alphadolone (3.90 mL min-1 (g tissue)-1) was significantly (P less
      than 0.05) greater than in rats anaesthetized with ketamine midazolam (3.24 mL
      min-1 (g tissue)-1, pentobarbitone (3.19 mL min-1 (g tissue)-1),
      fentanyl/fluanisone midazolam (2.84 mL min-1 (g tissue)-1) or urethane (1.99 mL
      min-1 (g tissue)-1). Renal blood flow in the urethane anaesthetized rats was
      significantly (P less than 0.05) lower than in animals anaesthetized with the
      other anaesthetic regimens, and is consistent with literature reports of a
      depressive effect of urethane anaesthesia upon xenobiotic renal clearance in the
      rat. Hepatosplanchnic blood flow was highest in the alphaxolone/alphadolone
      anaesthetized animals (71.7 mL min-1 kg-1), with the urethane anaesthetized
      animals demonstrating a significantly (P less than 0.05) lower (33.4 mL min-1 kg
      1) blood flow. The fentanyl fluanisone/midazolam (65.4 mL min-1 kg-1),
      pentobarbitone (61.1 mL min-1 kg-1), and ketamine/midazolam (51.4 mL min-1 kg-1)
      regimens resulted in hepatosplanchnic blood flows of intermediate magnitude. The
      observed marked differential effects of the anaesthetic regimens upon renal and
      hepatosplanchnic blood flows may dramatically influence drug disposition in the
      experimental animal, and be of significance to laboratory pharmacokinetic studies
      in which anaesthesia is used.

PMID- 1982141
TI  - Gonadal influence on the metabolism and haematological toxicity of dapsone in the
      rat.
AB  - Administration of dapsone (33 mg kg-1) to intact rats resulted in a marked
      elevation of methaemoglobin levels in male (435.0 +/- 105.2% met Hb h) compared
      with female rats (59.0 +/- 17.2% met Hb h). However, the clearance of dapsone was
      significantly faster in males compared with females. Female rats showed very low
      levels of methaemoglobin which were accompanied by significantly higher blood
      concentrations of parent drug. Clearance of dapsone in castrated animals was less
      than one-third of that of the intact sham-operated males (252.2 +/- 67.2 vs 81.4
      +/- 33.0 mL h-1). Likewise, clearance of dapsone in ovarectomized rats was
      approximately half that of intact females. There were no significant differences
      in the disposition of dapsone between the ovarectomized (AUC 431.0 +/- 31.7
      micrograms h mL-1; t1/2, 15.62 +/- 1.8 h) and castrated (AUC, 450.6 +/- 150.9
      micrograms h mL-1; t1/2, 17.6 +/- 7.9 h) animals. However, methaemoglobin levels
      in castrated males, although less than a third of those of intact males,
      significantly exceeded those of ovarectomized animals. There was no significant
      difference between the four groups of animals with respect to red cell
      sensitivity to the methaemoglobin-forming capacity of the toxic metabolite of
      dapsone, the hydroxylamine. Metabolic conversion of dapsone to the hydroxylamine
      in the presence of NADPH was 7.6 +/- 1.5% for liver microsomes from intact males
      and was significantly greater (P less than 0.05) than the corresponding values
      for liver microsomes from castrated rats (5.3 +/- 0.59%). Conversion of dapsone
      to dapsone-NOH by liver microsomes from intact females and ovarectomized animals
      was below 1% in both cases.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1982142
TI  - A possible reduction in the renal clearance of ciprofloxacin by fenbufen in rats.
AB  - The change in plasma concentration-time profile, serum protein binding and renal
      and biliary clearances of ciprofloxacin caused by coadministration of fenbufen
      has been studied in rats administered an intravenous dose of ciprofloxacin (5 mg
      kg-1) alone or with fenbufen (10 mg kg-1). Coadministered fenbufen significantly
      prolonged the plasma elimination half-life of ciprofloxacin from 40.5 to 57.6 min
      and tended to reduce the total body clearance of this quinolone by about 20%. The
      extent of ciprofloxacin binding to rat serum protein was not affected by
      fenbufen, nor did it affect the biliary clearance of the quinolone. However,
      fenbufen tended to reduce renal clearance and significantly decreased the
      cumulative renal excretion of the quinolone during at least the first 3 h after
      drug administration. These results suggest a possible reduction of ciprofloxacin
      clearance owing to inhibition of renal excretion by fenbufen.

PMID- 1982143
TI  - Pharmacokinetics of GM1 ganglioside following parenteral administration.
AB  - The pharmacokinetic parameters of monosialotetrahexosylganglioside (GM1) have
      been determined in healthy volunteers at 3 dose levels: 100, 200, 300 mg. Each
      dose was administered to separate groups of 12 volunteers. GM1 levels were
      determined in plasma, urine, and faeces by a method based on the property of the
      cholera toxin beta subunit to react specifically with GM1 ganglioside. A non
      compartmental model was applied to determine standard pharmacokinetic parameters.
      The average AUC increased with dose (1002 +/- 121.2, 1306 +/- 146.1, 3155 +/-
      121.6 micrograms mL-1 h after 100, 200, 300 mg, respectively). Plasma clearance
      was less than 3 mL min-1 and the distribution volume was close to the plasma
      volume (on average between 4.3 and 7.2 L). Mean residence time was about 43 h for
      all doses. GM1 was not detected in urine, while in faeces the amount of GM1
      determined was similar to the baseline values obtained before dosing.

PMID- 1982144
TI  - Renal responses to magnesium lithospermate B.
AB  - Renal responses to magnesium lithospermate B isolated from Salviae miltiorrhizae
      radix were examined in normal rats. Urinary sodium, potassium, prostaglandin E2
      and kallikrein excretion was significantly increased after magnesium
      lithospermate B administration, whereas excretion of urinary 6-keto-prostaglandin
      F1 alpha and thromboxane B2 was unchanged. Rats administered with the drug also
      revealed a slight elevation of plasma renin activity and the levels of
      angiotensins I and II. Plasma aldosterone was decreased slightly. No significant
      changes were observed in angiotensin-converting enzyme or blood pressure.

PMID- 1982145
TI  - Design of a polyvinyl alcohol hydrogen containing phospholipid as controlled
      release vehicle for rectal administration of (+/-)-propranolol HCl.
AB  - Polyvinyl alcohol hydrogels which contained phospholipid, egg yolk lecithin or
      hydrogenated soya lecithin were designed as a transrectal delivery system for
      propranolol hydrochloride. The hydrogel preparations containing phospholipid were
      prepared by a low-temperature crystallization method. The release profile of
      propranolol from hydrogel preparations containing phospholipid complied with
      Fickian diffusion (Higuchi model). The release of propranolol from the hydrogel
      preparation decreased with higher contents of phospholipid (approximately 2%
      w/w). In rats plasma concentrations of propranolol after rectal administration of
      hydrogel preparations containing phospholipid (1 and 2% w/w) were prolonged
      compared with those of rats receiving preparations without phospholipid.

PMID- 1982146
TI  - Inhibition of gastric H+, K(+)-ATPase by chalcone derivatives, xanthoangelol and
      4-hydroxyderricin, from Angelica keiskei Koidzumi.
AB  - Two chalcone derivatives, xanthoangelol (1) and 4-hydroxyderricin (II) isolated
      from Angelica keiskei Koidzumi, inhibited pig gastric H+, K(+)-ATPase with IC50
      values of 1.8 and 3.3 microM, respectively. The inhibition by I or II was
      competitive with respect to ATP and was non-competitive with respect to K+ I and
      II also inhibited K+, stimulated p-nitrophenyl phosphatase, with IC50 values of
      1.3 and 3.5 microM, respectively. Proton transport in-vitro was inhibited by I or
      II, in a dose-dependent manner, 1 at 100 mg kg-1, i.p. significantly inhibited
      acid secretion and the formation of stress-induced gastric lesions. These results
      suggest that the antisecretory effect of 1 is due to the inhibition of gastric
      H+, K(+)-ATPase.

PMID- 1982147
TI  - Comparison of intestinal and peritoneal dialysis of theophylline and
      phenobarbitone in rats.
AB  - Intestinal dialysis of drugs by oral administration of activated charcoal has
      been compared with peritoneal dialysis in rats. The average amounts of
      theophylline transported over 120 min into the intestinal lumen and the
      peritoneal cavity were 15.7 and 16.5% of the intravenous dose (10 mg kg-1),
      respectively, showing no significant difference, whereas the amount of the same
      intravenous dose of phenobarbitone transported from the blood into the intestinal
      lumen (7.8%) was significantly smaller than that entering the peritoneal cavity
      (12.5%). The net water flux showed that secretion predominated in the peritoneal
      transport whilst absorption predominated in the intestinal transport for both
      drugs. However, the net water flux in the intestinal lumen after intravenous
      theophylline (as aminophylline) was significantly smaller than that following
      phenobarbitone. The differences in transport across the two membranes could be
      due to differences in the intrinsic properties of the could be due to differences
      in the intrinsic properties of the membranes, such as the surface area, the
      thickness of the membrane and the distribution of blood vessels. Differences
      could also be due to differences in the pharmacological effects of the drugs.

PMID- 1982148
TI  - Distribution of griseofulvin in the rat: comparison of the oral and topical route
      of administration.
AB  - Effective penetration of griseofulvin across the dermal barrier has been achieved
      using an anhydrous solvent system of benzyl alcohol (10%), acetone (40%), and
      isopropanol (50%). There were quantitative differences in the relative
      accumulation of griseofulvin in skin compared with internal organs, when the
      topical and oral routes of administration were compared. The topical route
      enhanced localized concentrations of griseofulvin at the site of application, and
      these persisted for several days. After daily topical application a steady state
      was reached at day 3, when the diffusion across the skin barrier and epidermal
      loss seemed to equal the total amount applied to the skin surface. The
      application of griseofulvin topically, required a much smaller amount of drug to
      achieve similar integumentary levels compared with the amount required orally.

PMID- 1982149
TI  - The excitatory effect of dopamine on isolated canine tracheal smooth muscle.
AB  - The effect of exogenous dopamine on canine tracheal smooth muscle has been
      studied in-vitro. Dopamine at concentrations over 10(-5)M induced contractions of
      tracheal muscle strips and repeated exposures resulted in desensitization
      (tachyphylaxis) of the muscle. The sensitivity of the response varied
      dramatically among muscle strips. At lower concentrations, dopamine caused
      neither muscle relaxation nor inhibition of contractions evoked by 10(-6)M
      acetylcholine. Both a dopaminergic antagonist, haloperidol (10(-5) and 10(-4)M),
      and an alpha-adrenoceptor antagonist, phentolamine (10(-7) to 10(-5)M),
      attenuated the contraction to 10(-3)M dopamine. The beta-adrenoceptor antagonist,
      propranolol (10(-8) to 10(-6)M), enhanced the contraction. However, the
      contraction could only be abolished by phentolamine at 10(-4) M. Thus, in canine
      tracheal smooth muscle, the contractile response to dopamine is predominantly
      through the activity of alpha-adrenoceptors and the role of dopaminergic
      receptors is vague. It is suggested that the weakness of the dopamine-induced
      contraction results from an antagonism between alpha- and beta-adrenoceptor
      effects and the dopamine tachyphylaxis may reflect a gradually decreased
      activation of the alpha-adrenoceptor mechanism in comparison with the beta
      adrenoceptor mechanism.

PMID- 1982150
TI  - Effects of clenbuterol treatment on the responses to vasodilators in urethane
      anaesthetized rats.
AB  - Seven or 14 days of treatment with the beta 2-adrenoceptor agonist clenbuterol,
      0.3 mg kg-1, s.c., twice daily, increased the basal mean blood pressure in
      normotensive urethane-anaesthetized rats. The elevated pressure values were
      maintained until 48 h after the end of the 14 day treatment. Clenbuterol
      treatment decreased the vasodilatory responses to the beta-adrenoceptor agonist
      isoprenaline and adenosine, agents which act through an increase in intracellular
      cyclic AMP. Decreased responses were maintained until 48 h after a 14 day
      treatment with clenbuterol. On the other hand, its administration to rats for 14
      days did not modify the vasodilator responses to acetylcholine or sodium
      nitroprusside, two agents that exert their effects by enhancing cyclic GMP. The
      increase in mean blood pressure in urethane-anaesthetized rats after clenbuterol
      treatment may be a consequence of a reduced vasodilator beta 2-adrenoceptor
      mediated response to circulating catecholamines.

PMID- 1982151
TI  - Effect of naproxen sodium on the net synthesis of glycosaminoglycans and protein
      by normal canine articular cartilage in-vitro.
AB  - The effects of the non-steroidal anti-inflammatory drug, naproxen sodium, on the
      metabolism of normal canine articular cartilage has been examined. At a
      concentration approaching that achieved in synovial fluid of patients treated
      with the drug (i.e. 30 micrograms mL-1) naproxen sodium had no significant effect
      on net synthesis of either glycosaminoglycans or protein in organ cultures of
      femoral condylar cartilage, nor did it increase the proportion of newly
      synthesized glycosaminoglycans recovered from the culture medium, suggesting that
      it had no direct effect on the integrity of the extracellular matrix.

PMID- 1982152
TI  - Acute treatment with clonidine or calcium entry blockers on opioid withdrawal in
      guinea-pig ileum.

PMID- 1982153
TI  - Bivalent effects of human growth hormone in experimental myocardial infarcts.
      Protective when administered alone and aggravating when combined with beta
      blockers.
AB  - Human growth hormone (hGH) administered alone revealed itself as a useful drug to
      prevent ventricular aneurysm formation in experimental myocardial infarctions in
      rats and is also able to diminish and change the usually expected pattern of wall
      necrosis. A protective action on the collagen framework of myocytes has been
      confirmed as one of the main causes responsible for the above mentioned findings.
      There are other positive metabolic actions on the myocardial cell although not
      completely known yet. These actions are revealed by an atypical picture of
      infarction which appears regionally reduced and with a patchy intracellular
      distribution. In an opposite fashion, when hGH was administered together with
      beta blockers, a rapid and extensive deleterious action occurred at the
      ventricular wall, a very high incidence of ventricular aneurysms and an increased
      extension of myocardial infarcts were the most outstanding features. The
      histologic picture in this series resembles that of a rapidly evolving diabetic
      cardiomyopathy.

PMID- 1982154
TI  - [Effect of anapriline on myocardial contraction and systemic vascular resistance
      in patients with stage II hypertension].

PMID- 1982155
TI  - [Changes in prostaglandin levels in the blood of patients with various forms of
      chronic colitis before and after treatment].
AB  - Plasma prostaglandins have been studied in 306 patients with chronic nonspecific
      ulcerative colitis. These were found elevated and related to the disease gravity.
      Treatment succeeded in normalizing prostaglandin, concentrations only in mild
      ulcerative colitis. In catarrhal pancolitis PGE levels moderately increased
      before treatment returned to normal at the end of it. In spastic colon
      pretreatment lack of PGF2 alpha persisted. Evaluation of plasma prostaglandins
      can serve an additional diagnostic procedure to improve pathogenetic therapy of
      chronic colitis.

PMID- 1982156
TI  - [Analysis of fatal outcome in hemorrhagic fever with renal syndrome].
AB  - The analysis of 88 lethal outcomes of hemorrhagic fever with renal syndrome
      (HERS) showed the occurrence of adenohypophyseal hemorrhage and necrotic foci in
      75.5% of cases as well as combined involvement of adenohypophysis and adrenals in
      18.4%. Pathogenetically, adenohypophyseal affection is related to anatomical
      physiological features of the vessels, microcirculatory disorders, acute venous
      congestion. Contributing factors may be acute DIC syndrome, relapsing and
      prolonged collapses, hyperhydration leading to brain edema and hemostasis.
      Uncontrollable vomiting recorded in all the deceased patients seemed to promote
      destruction of adenohypophysis. Clinically, this gross pathomorphology ++ was
      equivalent to severe form of the disease--hypopituitary coma. Proper prophylaxis
      of the above complications is one of the conditions entailing reduction of
      mortality in HFRS.

PMID- 1982157
TI  - Identification and purification of murine hematopoietic stem cells by flow
      cytometry.

PMID- 1982158
TI  - [The effect of the "37 degrees C--low pH" signal on cells of Yersinia pestis].
AB  - It is established that the synthesis of adhesion piles registered by the results
      of immunoenzyme analysis and immunoblotting starts 90 min after the action on
      apilated cells of plaque microbe EB-76 of the signal "37 degrees C-low pH"
      (cultivation at 37 degrees C and acidic pH). Under these conditions a part of
      cell piline is in a form connected with cells and only inconsiderable part (to
      20%) is represented in a form of "classical" piles possessing hemagglutinating
      activity. It is shown that in first 7h after the interaction of the signal "37
      degrees-low pH" synthesis of adhesion piles quantitatively prevails over the
      synthesis of antigen of the fraction I of plaque microbe.

PMID- 1982159
TI  - [The dynamics of the EEG indices of the brain sensory systems during mental
      activity with modality-specific information presentation].

PMID- 1982160
TI  - Experimental brain ischaemia: assessment of injury by magnetic resonance
      spectroscopy and histology.
AB  - Phosphorus magnetic resonance spectroscopy (31P-MRS) was made to measure changes
      in brain high energy phosphate compounds, adenosine triphosphate (ATP) and
      phosphocreatine (PCr), inorganic phosphorus (Pi) and intracellular pH (pHi)
      during a prolonged period of incomplete brain ischaemia produced, in
      anaesthetized dogs, by bilateral carotid occlusion together with haemorrhagic
      hypotension for intervals of up to 300 min. Mean arterial blood pressure (MABP)
      was lowered in a stepwise fashion, until signs of metabolic decompensation (as
      estimated by MRS) occurred. At that point MABP was varied against further
      evidence of metabolic decompensation in an attempt to maintain a more constant
      degree of insult. At the end of the ischaemic period MABP was restored and the
      animals observed during a 3 h recovery period. At the end of the recovery period
      the brains were perfusion-fixed for histological examination. A semi-quantitative
      method of histological evaluation was used to determine the degree of
      histological damage. This permitted assignment of an 'ischaemic score' to the
      tissue sampled from each animal. Comparisons were then made between the magnitude
      of this 'ischaemic score' and the changes in metabolic and physiological
      variables (ATP, PCr, pHi and MABP) as well as an estimator of phosphorylation
      potential (PCr/Pi), which were all measured during the ischaemic insult.
      Histological examination showed a wide variety of neuronal alterations, including
      dark and pale type injury, which correlated directly with the metabolic
      derangements brought about by ischaemia. The degree of damage determined from
      this histological assessment correlated best with the duration and degree of
      change in PCr/Pi, supporting the use of this ratio as a critical index of
      cellular energy state. In particular there was a strong linear relationship
      between the degree of leucocyte recruitment and changes in PCr/Pi. To summarize,
      metabolic changes, determined by MRS, correlate with the degree of histological
      damage, and in turn, the classical descriptions of acute ischaemic neuronal
      injury appear to be validated by MRS determinations of metabolic changes during
      ischaemia.

PMID- 1982161
TI  - Transcranial Doppler monitoring in severe brain damage: relationships between
      intracranial haemodynamics, brain dysfunction and outcome.
AB  - Transcranial Doppler (TCD) monitoring in the middle cerebral (MCA) and common
      carotid arteries (CCA) was studied in 105 comatose patients with severe brain
      damage. TCD-measured velocity waveforms in the MCA were evaluated in relation to
      loss of cerebral function as assessed by EEG and compressed spectral arrays, loss
      of brain stem function as measured by somatosensory and auditory evoked
      potentials, loss of all brain function and the clinical outcome. The velocity
      waveforms exhibited six patterns: continuous forward flow (FF); diastolic no flow
      (NF); diastolic reverse flow with (RF) or without (DRF) diastolic FF; brief
      systolic FF (SFF); and undetectable (U). In the 58 fatal cases, the appearance of
      RF/DRF or SFF in the MCA more often preceded loss of brain stem function than
      loss of cerebral function. A U pattern in the MCA, which was confirmed by loss of
      FF in the CCA, was correlated with loss of brain stem function. Only one of the
      47 survivors showed DRF in the MCA. No patients in whom SFF or U was observed in
      the MCA survived. Therefore the presence of these patterns is reliably predictive
      of brain death. Intracranial diastolic reverse flow (DRF), however, indicates
      imminent loss of brain function and the need for prompt resuscitative measures.

PMID- 1982162
TI  - Postoperative monitoring of cerebral blood flow in patients harboring
      intracranial aneurysms.
AB  - Fifteen patients harbouring intracranial aneurysms were monitored
      postoperatively. A thermal diffusion flow probe was placed on the cortex, in an
      area of interest, and continuous recording of cerebral blood flow (CBF) was
      carried out for 1-4 days. Vasospasm can also be detected by clinical
      deterioration, increased velocity by transcranial Doppler, and by angiographical
      evidence of decrease in vessel calibre. A comparison was made between these
      methods of determining vasospasm and changes in CBF. Three patients had
      unruptured aneurysms and no evidence of vasospasm. These patients had a range of
      CBF from 44 to 100 cc 100 g-1 min-1 with a daily mean of 78 cc 100 g-1 min-1. One
      patient was operated on, in a delayed fashion, after a period of vasospasm on
      post-subarachnoid haemorrhage (SAH) Day 18 and was found to have a CBF of 40 cc
      100 g-1 min-1 when the pCO2 was 21 Torr and the mean blood pressure (BP) was 99
      Torr. The development of vasospasm was correlated with a CBF of less than 40 cc
      100 g-1 min-1. Some patients with vasospasm also develop a significant drop in
      CBF during the period of monitoring. Using these criteria, CBF monitoring
      predicted the development of vasospasm in seven patients, was compatible with the
      clinical course in three patients and was misleading in two patients. In the
      seven patients in which CBF predicted vasospasm, changes were seen in CBF prior
      to changes observed by clinical examination, transcranial Doppler, and/or
      angiography.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1982163
TI  - Oxygen protects rat brain from ischaemic injury.
AB  - Interruption of the oxygen supply to the brain promotes functional and structural
      damage of the brain, such as oedema and swelling. The most prominent cellular
      reaction to this type of damage has been found to be trophic or proliferative
      changes in glial cells. We examined dynamic changes in glial cells adjacent to
      the infarcted tissue in response to oxygenation. Results showed that astrocyte
      proliferation was seen more at 3 than at 7 days after middle cerebral artery
      occlusion, while their numbers with and without oxygenation were almost the same.
      The proliferation of microglia, however, was seen more with than without
      oxygenation. However, microglia seem to be able to secrete an angiogenetic factor
      under hypoxic conditions, and are active in terms of superoxide dismutase (SOD).
      Cerebral blood flow is directly related to tissue oxygen content and its
      autoregulatory capacity has been found to be greater as the volume contracts. As
      a result, we suggest that the application of oxygen-treated microglia to
      ischaemic tissue could diminish tissue damage, and that the most effective
      oxygenation can be achieved by the withdrawal of blood and reduction of the
      intracranial pressure.

PMID- 1982164
TI  - A guanine nucleotide-binding protein in human astrocytoma.
AB  - We compared, by immunoblotting and immunohistochemical staining, the distribution
      of the alpha subunit of Go in human normal brain tissue with that in human brain
      tumours of neuroectodermal origin. The ten tumour samples included seven high
      grade astrocytomas (grades III and IV) and three low-grade astrocytomas (grade
      II). Immunoreactivity of high-grade astrocytomas with the alpha subunit of Go (Go
      alpha) antibody was lower than that of low-grade astrocytomas and normal white
      matter. In the immunohistochemical study, neoplastic cells in the astrocytomas
      were found to contain little or no significant Go alpha, although nonlesional
      white matter was strongly stained with Go alpha antibody. This study suggests
      that Go alpha antibody may assist in defining the boundary of an astrocytoma, and
      the difference in Go content may affect the alteration in the physical properties
      of the membrane, which exhibit, in part, the character of the transformation.

PMID- 1982165
TI  - Increased cerebral blood flow in idiopathic pseudotumour cerebri.
AB  - Cerebral blood flow was studied in nine patients with idiopathic pseudotumour and
      one patient with cortical vein thrombosis in Denver, Colorado using the 133Xe
      inhalation method. Globally elevated blood flows were found in all of the
      idiopathic pseudotumour patients averaging 149% of control values generated in
      the same setting. The patient with the cortical vein thrombosis demonstrated
      normal global flows. Possible pathophysiological mechanisms for these findings
      are discussed.

PMID- 1982166
TI  - Time-sequential change of amino acid neurotransmitters--GABA, aspartate and
      glutamate--in the rat basal ganglia following middle cerebral artery occlusion.
AB  - To clarify the involvement of neurotransmitters in the remote metabolic effect
      following focal ischaemia, amino acid neurotransmitter candidates--GABA,
      aspartate and glutamate--were measured time-sequentially in the basal ganglia
      following middle cerebral artery occlusion in the rat, which is known to produce
      a change in glucose metabolism and blood flow in the remote basal ganglia. GABA
      and aspartate content decreased in the ipsilateral substantia nigra from the
      second to the 28 th postoperative day. The same tendency was observed in the
      ipsilateral globus pallidus. Glutamate did not change significantly in either
      nucleus. In the contralateral side, GABA increased significantly in the
      substantia nigra throughout the experimental period and in the striatum during
      the first seven days. These results indicate that the destruction of strionigral
      tract by focal ischaemia induced the decrease of inhibitory GABA in the
      ipsilateral substantia nigra. The increase of metabolism in this nucleus may be
      caused by the decrease of the inhibitory effect.

PMID- 1982167
TI  - Unilateral carotid artery ligation in the Mongolian gerbil as a model for testing
      infarction-reducing therapies.
AB  - This study evaluates infarct size measurement as an indicator of cerebral
      ischaemia outcome in a placebo-controlled trial of potential cerebral protection
      in the unilateral carotid artery ligation in the Mongolian gerbil. Ibuprofen was
      used in an effort to manipulate infarct size as this agent has been shown to
      reduce ischaemia in myocardial infarction. Using measurements obtained through an
      infarct-sizing technique and a statistical power analysis of the method, the
      sample sizes needed to obtain significant results were projected for this model.
      In this case, it was not possible to demonstrate an effect of ibuprofen on
      infarct size although a tendency towards larger infarct size in ibuprofen-treated
      compared with placebo-treated gerbils was observed (36.1 +/- 10.1% versus 30.0 +/
      17.5%). The sample sizes needed to find significant changes in infarct size
      indicate that this model finds a practical use in studying therapies which will
      alter infarct size by at least 50%. For example, to detect a 30% change in
      infarct size, 33 successfully infarcted gerbils per group would be needed, but a
      50% change would require a more tenable 13 infarcted gerbils per group. However,
      given the 40% infarction rate of occluded gerbils seen in this study, almost 33
      gerbils per group would be required to detect a 50% change. In addition,
      somatosensory evoked potential was compared with neurological examination as a
      predictor of infarction. It would be helpful to be able to pre-screen for
      infarcted gerbils immediately after occlusion in order to direct infarcted
      gerbils into control and treated groups. Somatosensory evoked potential
      successfully predicted infarction with a 90% accuracy in 21 gerbils compared with
      neurological evaluation which was 100% accurate. But the somatosensory evoked
      potential prediction was made within 15 min of occlusion as opposed to the 6 h of
      observation during which the neurological evaluation was made.

PMID- 1982168
TI  - Brain mitochondrial redox state, tissue haemodynamic and extracellular ion
      responses to four-vessel occlusion and spreading depression in the rat.
AB  - Fibre-optic surface fluorometer reflectrometry was used to monitor the NADH
      (nicotine adenine dinucleotide) redox state from rat brain during three- or four
      vessel occlusion. To compare the completeness of the electrocauterization of the
      vertebral arteries and the effectiveness of the anterior cerebral arteries, two
      light guides were implanted above the cerebral hemispheres. The NADH level was
      measured and correlated with the changes in the intensity of the reflected light
      at the excitation wavelength (366 nm) and to the ECoG (electrocorticogram). In
      the present study, we used ten rats in which unilateral and bilateral carotid
      occlusion were performed. In a second group of rats we tested the effects of four
      vessel occlusion on the metabolic and extracellular K+ and Ca2+ activities as
      compared with those recorded under spreading depression conditions. These
      experiments were done by using the multiprobe assembly (MPA) approach. The
      results could be summarized as follows: (1) in the four-vessel occlusion model,
      the level of cerebral ischaemia could be estimated quantitatively, in real-time,
      by monitoring the NADH redox state; (2) unilateral carotid occlusion (after
      vertebral coagulation) led to a variable level of ipsilateral ischaemia,
      depending upon the blood flow compensation between the two hemispheres; (3) fibre
      optic fluorometry enabled the correlation of NADH redox state with other
      physiological parameters as well as during after-brain ischaemia; (4) using the
      MPA in rats exposed to four-vessel occlusion as well as spreading depression, we
      identified the differences between the two pathological states, although there
      were some similarities in the ion homeostasis responses.

PMID- 1982169
TI  - Pathogenesis and histopathology of saccular aneurysms: review of the literature.
AB  - In this paper, the major theories on the formation and growth of saccular
      aneurysms are reviewed on the basis of previous clinical, pathological and
      experimental studies. Which is the critical layer is still the focus of debate.
      Current ideas can be summarized as follows: most researchers think that
      disruption of the internal elastic lamina is an essential requirement for the
      creation of saccular aneurysms because it is this layer that provides most of the
      strength to the arterial wall, especially in cerebral arteries. Degeneration of
      this layer is a constant feature of all saccular aneurysms. A coexisting medial
      defect and haemodynamic stress at an apex may aggravate degeneration at that
      point. Hypertension does not seem to be the major factor in some aneurysm
      patients, but it may facilitate the formation and growth of saccular aneurysms.
      An atheroma is often associated with saccular aneurysms, but its effect on this
      pathological process is still unknown. Other factors are discussed concisely.
      Previous experimental methods and their results pertaining to the formation and
      growth of this type of aneurysm are also reviewed. A reproducible animal model is
      still required to allow various theories to be tested.

PMID- 1982170
TI  - An acute experimental model of saccular aneurysms in the rat.
AB  - A new and reproducible saccular aneurysm model has been developed at the
      bifurcation of the common carotid artery in rats. The details of the experimental
      methods and results are described. It is strongly suggested that the internal
      elastic lamina is a critical layer in saccular aneurysm formation, because an
      experimental saccular aneurysm can be produced immediately by transluminally
      damaging the inside of the arterial wall at the bifurcation of the common carotid
      artery. This saccular aneurysm model has several advantages: (i) it can be
      induced quickly and the success rate approaches 100% in rats; (ii) this technique
      can produce satisfactory experimental saccular aneurysms for other aneurysm
      studies, and in the future it will also be possible to use this technique to
      produce experimental saccular aneurysms in cerebral arteries of large animals.

PMID- 1982171
TI  - Observations on experimental saccular aneurysms in the rat after 2 and 3 months.
AB  - After 2 and 3 months we re-exposed 20 experimental saccular aneurysms. Under the
      operating microscope, we measured their sizes and compared them with the sizes
      immediately after induction. All aneurysms had grown significantly and none was
      thrombosed. Pathological examinations showed that the sac of the aneurysm was
      similar to that of the human saccular aneurysms. Based on the operating
      microscopy and pathological findings we postulate that abnormal histological
      structure and haemodynamic stress are the major causes of aneurysm enlargement.
      We also noted that there were some regenerative processes in these experimental
      aneurysm walls. The results prove that this model is reliable, because these
      aneurysms have the main characteristics of human saccular aneurysms, not only
      grossly but also microscopically.

PMID- 1982172
TI  - Immunotherapy for recurrent malignant glioma: an interim report on survival.
AB  - We present interim survival data for a group of 83 adult patients with recurrent
      malignant glioma treated by implanting stimulated autologous lymphocytes into the
      tumour bed following surgical debulking. The patients were treated 6 months or
      more prior to data analysis. Fifty-nine patients were male and 24 female. The
      mean age for the entire group was 48.4 years and the mean Karnofsky rating (KR)
      was 67.2. Eight of the patients had grade II tumours, 33 had grade III tumours
      and 42 had grade IV tumours. Statistical analysis focuses on tumour grade, KR and
      patient age, factors that have been shown to affect survival in previous studies.
      Multifactorial analyses are employed to identify interrelationships among factors
      related to survival. Seven patients (8%) did not respond to immunotherapy, 76
      (92%) had a good initial response. Twenty-five patients (30.1%) are living and 18
      (22%) have shown no evidence of recurrence. Results are evaluated in the light of
      those obtained in trials of other experimental therapies for recurrent malignant
      gliomas. It is concluded that the present protocol offers a safe and
      comparatively effective treatment option.

PMID- 1982173
TI  - Effect of antisecretory factor on Escherichia coli STa enterotoxin-induced
      alkalinisation of pig jejunal acid microclimate.
AB  - The effect of challenge by Escherichia coli STa enterotoxin on pig jejunal
      mucosal surface pH was investigated in vivo. Exposure to STa resulted in a rapid
      and reversible alkalinisation (P less than 0.001) of the jejunal mucosa from 6.27
      +/- 0.11 (5) to 6.89 +/- 0.03 (5). This action of STa is probably mediated
      through cyclic 3'5'-guanosine monophosphate (cGMP) since the 8-bromo analogue of
      cGMP induced the same effect as that observed after STa challenge. The action of
      STa on mucosal pH was partially inhibited by pre-administration of an
      antisecretory factor (ASF) preparation. The action of 8-bromo cGMP was unchanged
      by the presence of ASF. This implies that ASF inhibition occurs during the early
      stages of STa action prior to stimulation of guanylate cyclase. This effect of
      STa on the pig jejunal mucosal surface pH, or acid microclimate, may explain why
      weak acid supplementation of oral rehydration solutions can be ineffective in
      certain types of diarrhoeal disease.

PMID- 1982174
TI  - Beta-adrenoceptor-mediated depolarization of the resting membrane in guinea-pig
      papillary muscles: changes in intracellular Na+, K+ and Cl- activities.
AB  - Effects of beta-adrenergic stimulation on the membrane potential and
      intracellular Na+, K+ and Cl- activities were examined in isolated guinea-pig
      ventricular muscles using conventional and ion-selective electrodes.
      Isoproterenol in concentrations of 30 nM - 1 microM produced a transient
      depolarization followed by a slight hyperpolarization in electrically stimulated
      or quiescent papillary muscles. The negative logarithm of the concentration
      producing 50% maximum effect (pD2) for the membrane-depolarizing effect of
      isoproterenol was smaller than that for the positive inotropic effect, suggesting
      that a higher level of cAMP accumulation is required to produce the transient
      depolarization. Whereas the isoproterenol(1 microM)-induced depolarization was
      not blocked by tetrodotoxin (10 microM), nifedipine (10 microM), Cs+ (5 mM), Ba2+
      (0.3 mM), amiloride (1 mM) or ouabain (10 microM), it was significantly
      attenuated by anthracene-9-carboxylic acid (1 mM), a Cl(-)-channel blocker.
      Intracellular K+ activity increased, whereas intracellular Na+ activity slightly
      decreased during the transient depolarization. Intracellular Cl- activity
      significantly decreased during the isoproterenol-induced depolarization of the
      resting membrane. These results suggest that an inward current resulting from
      outward Cl- movement, rather than inward Na+ movement, may be involved in the
      beta-adrenoceptor-mediated membrane depolarization.

PMID- 1982175
TI  - Gastrin- and somatostatin-immunoreactive cells of the antral mucosa in patients
      with duodenal or gastric ulcers. An immunocytochemical study.
AB  - Gastrin- and somatostatin-immunoreactive cells in biopsies taken from the
      prepyloric portion of the antrum from 15 patients with duodenal ulcer, 16
      patients with gastric ulcer, and a control group of 19 patients without
      histopathological alterations of the antral mucosa were studied using peroxidase
      anti-peroxidase and immunogold-silver staining methods in combination with
      morphometry. Numerical densities and sizes (immunoreactive areas) of the cells
      demonstrated were measured and compared between all three groups. Gastrin- and
      somatostatin-immunoreactive cells were located most frequently in the lower
      midzone of the gastric crypts. None of the parameters measured showed a
      correlation with age or sex. The group with duodenal ulcer tended to exhibit
      gastrin- and somatostatin-cell-hyperplasia whereas the size of both cell types
      remained unchanged. In comparison with the control group, the numerical density
      of gastrin-immunoreactive cells was significantly increased in gastric ulcer
      patients, whereas the numerical density of somatostatin-immunoreactive cells was
      decreased in this group. Immunoreactive areas of both cell types were
      significantly increased in patients with gastric ulcer.

PMID- 1982176
TI  - 8th congress of USSR pathologists.

PMID- 1982177
TI  - [Current methods of DNA sequencing].

PMID- 1982178
TI  - The drug management of severe alcohol withdrawal syndrome.
AB  - We describe the various phases of the alcohol withdrawal syndrome with special
      reference to the pitfalls of using neuroleptics. We outline the importance of
      adequate sedation using either benzodiazepines or chlormethiazole. We provide a
      critical appraisal of the currently employed anti-epileptic medication in the
      alcohol withdrawal syndrome. We also indicate the usefulness of analgesic nitrous
      oxide as a screening test in differentiating the cases of alcohol withdrawal
      syndrome needing further intensive therapy to prevent progression to delirium
      tremens.

PMID- 1982179
TI  - Adrenoceptors in airway smooth muscle.
AB  - This review examines the roles and functional significance of alpha and beta
      adrenoceptor subtypes in airway smooth muscle, with emphasis on human airway
      function and the influence of asthma. Specifically, we have examined the
      distribution of beta-adrenoceptors in lung and the influence of age, the
      epithelium, respiratory viruses and inflammation associated with asthma on airway
      smooth muscle beta-adrenoceptor function. Sites of action, beta 2-selectivity,
      efficacy and tolerance are also examined in relation to the use of beta 2
      agonists in man. In addition, alpha-adrenoceptor function in airway smooth muscle
      has been reviewed, with some emphasis on comparing observations made in airway
      smooth muscle with those in animal models.

PMID- 1982180
TI  - Pharmacological properties of the stimulant khat.
AB  - The chewing of the stimulant leaf khat is a habit that is widespread in certain
      countries of East Africa and the Arabian peninsula. During the last decade,
      important progress has been made in understanding the pharmacological basis for
      the effects of khat. It is now known that the CNS action of this drug is due to
      the presence of the alkaloid cathinone, and the results of various in vitro and
      in vivo experiments indicate that this substance must be considered a natural
      amphetamine. It is the purpose of the present review to describe briefly the khat
      habit and to summarize the pharmacology of khat and of its active constituents.

PMID- 1982181
TI  - Receptor-regulated calcium entry.
AB  - A wide variety of hormones and neurotransmitters activate cellular responses by
      mobilizing cellular Ca2+. In general, this Ca2+ mobilization response is
      comprised of a release of Ca2+ from intracellular stores, as well as increased
      entry of Ca2+ into the cytoplasm from the extracellular space. The mechanism for
      release of intracellular Ca2+ results from the Ca2(+)-mobilizing actions of a
      second messenger, D-myo-inositol 1,4,5-trisphosphate. Inositol polyphosphates
      appear also to be involved in the activation of Ca2+ entry, but the mechanism by
      which this is accomplished is less clear. According to the capacitative model for
      Ca2+ entry, the depletion of the agonist-regulated intracellular Ca2+ pool by the
      action of D-myo-inositol 1,4,5-trisphosphate is somehow coupled to the activation
      of Ca2+ entry. The evidence for this model comes from the demonstration, by
      diverse strategies, that the same Ca2+ entry mechanism normally activated by
      Ca2(+)-mobilizing agonists can be equally well triggered by depletion of the
      intracellular Ca2+ pool, even in the absence of receptor activation or elevated
      cellular levels of inositol polyphosphates.

PMID- 1982182
TI  - [Biochemical markers in relation to the degree of alcohol dependence].
AB  - In 93 alcohol dependent patients following laboratory tests were done: gamma
      glutamic transpeptidase (GGTP), aspartate aminotransferase (SGOT), mean
      erythrocyte volume (MCV), triglycerides (TGL), and HDL-cholesterol to whole
      cholesterol ratio (HDLC%). The psychometric evaluation was made by MAST
      questionnaire and by authors clinical scale for the evaluation of alcohol
      dependence. Lover values of GGTP and SGOT were shown in patients during
      abstinence than in subjects continuing drinking. Patients more severely dependent
      showed higher HDLC%. The more frequent abnormalities reflected: GGTP (33.7%), MCV
      (33.7%), and HDLC (31.4%). The use of these 3 markers allowed to reveal
      abnormalities in 72.1% of subjects, while the use of all 5 markers - in 81.4%.
      The identification significance of markers was different in persons with more and
      less severe alcohol dependence. Three most sensible markers in the group of less
      dependent subjects were GGTP, MCV, TGL (60% of subjects showed abnormalities
      regarding these markers). Among more severe dependent subjects HDLC%, GGTP, and
      MCV were most sensible markers (78.4% of abnormalities). Using all 5 markers the
      abnormalities in the group of less severe dependent subjects were found in 71.4%,
      and in the group of more severe dependent patients--in 88.2%.

PMID- 1982183
TI  - [Psychotropic effect of clonidine--the role of alpha 2 adrenergic receptors in
      the pathogenesis of mental disorders].

PMID- 1982184
TI  - Clinical pharmacology and Leonhard's classification of endogenous psychoses.
AB  - Introduction of therapeutically effective psychotropic drugs focused attention on
      the heterogeneity of psychiatric populations within the traditional diagnostic
      categories of psychiatric disorders. Recognition that valid diagnostic concepts
      are essential for progress in the biology and pharmacotherapy of psychiatric
      disorders resulted in a revival of interest in psychiatric nosology with a
      special emphasis on Leonhard's classification of 'endogenous psychoses'. Of
      particular importance for psychopharmacology in Leonhard's system is the
      recognition of two distinctive populations within the schizophrenic disorders,
      i.e., 'unsystematic schizophrenias' and 'systematic schizophrenias'; three
      distinctive populations within the bipolar disorders, i.e., 'manic-depressive
      illness,' 'cycloid psychoses' and 'unsystematic schizophrenias'; and two
      distinctive populations within depressive disorders, i.e., 'unipolar depression'
      and 'bipolar depression'. In this paper supporting data for Leonhard's
      classification of 'endogenous psychoses' are presented.

PMID- 1982185
TI  - [Current findings in hepatic fibrogenesis].

PMID- 1982186
TI  - [Nuclear stethoscopy. The clinical technic, methods and applications].
AB  - The paper reports on a new way of cardiological, radionuclidic investigation of
      the patients, a technique used for the first time in Romania. The technique and
      investigation method are presented in detail, with emphasis on some more
      important stages. As resulting from the description of the methodology, the
      performances of the left ventricle consist of three types of radioactivity/time
      curves at: first passage, beat by beat, and their summation. Of the advantages
      offered by the nuclear stethoscope, mention should be made that, besides the
      evaluation of systolic and diastolic parameters, it monitors the left ventricle
      functions in the rhythm disturbances, beat by beat, and being mobile, it permits
      the investigation at the patient's bed. Finally, the paper presents several cases
      investigated by the authors, and their special clinical applicability.

PMID- 1982187
TI  - [Current developments in the diagnosis and treatment of periarteritis nodosa].

PMID- 1982188
TI  - [Silent myocardial ischemia].

PMID- 1982189
TI  - [The cholestasis syndrome. A critical evaluation of an exploratory strategy].
AB  - The authors studied 160 cases of biliary stasis: 120 having intrahepatic cause
      (101 hepatic cirrhoses and 19 primitive biliary cirrhoses) and 40 extrahepatic
      cause (17 choledochal lithiases and 23 cancers of the pancreas head) and check up
      the diagnosis value of two investigation algorithms: echography, the first
      investigation, followed by hepatic biopsy puncture, if the intrahepatic biliary
      ducts are not dilated, or transhepatic cutaneous cholangiography if the
      intrahepatic biliary ducts are dilated in comparison with intravenous
      cholangiography in the first investigation. Echography has an increased diagnosis
      yield (96% sensitivity, 99% specificity), is cheap, noninvasive and is the first
      imaging exploration used in biliary stasis syndrome.

PMID- 1982190
TI  - [Early cirrhosis, an early modality of the evolution of acute hepatitis. The
      clinico-biological, immunological and morphological aspects].
AB  - A group of 12 patients with recent acute hepatitis (8/86 with HVB and 4/22 with
      alcoholic hepatitis) had a rapid evolution (under 2 years) towards hepatic
      cirrhosis (early H.C.). The clinical-biological, immunological and morphological
      study made evident several characteristics, which became predictive markers of
      the early cirrhotic evolution of acute hepatitis. Clinically, a persistence of
      dyspeptic disorders and appearance of several systemic manifestations is noticed.
      Biologically, the maintenance of some increased transmainases, variable
      bilirubinemia and decrease of serinemia. Immunologically, the transfer of IgM
      towards increased IgM, the decrease of the total T lymphocyte and of T1
      substrate, the increase of the active B and T lymphocyte. The morphologic
      exploration is decisive for specification of the diagnosis in the early hepatic
      cirrhosis.

PMID- 1982191
TI  - [Bacterial immunofluorescence in the intestinal juice in relation to other
      cellular and humoral immunity factors in the intestinal juice and blood serum of
      patients with chronic nonspecific enteropathy].

PMID- 1982192
TI  - [Nifedipine pharmacokinetics in liver cirrhosis patients after the administration
      of a single oral dose].
AB  - The niphedipine pharmacokinetics was investigated in the patients with hepatic
      cirrhosis, in comparison with a group of healthy subjects, after administering
      unique doses of 10 mg per os. The niphedipine concentrations in serum were
      determined by a gas chromatography method. The niphedipine pharmacokinetics may
      be described in correspondence with the open pharmacokinetic model. The values of
      pharmacokinetic parameters of niphedipine in the patients with hepatic cirrhosis
      are significantly modified in comparison with those noticed in the healthy
      subjects. An increase in the level of the maximum concentrations (158 ng/ml
      versus 68 ng/ml), of the biological half time (11.9 hours versus 2.5 hours) and
      of the area under the curve of the drug concentrations in time (450 ng.ml-1.hour
      versus 205 ng.ml-1.hour) were found. The relative bioavailability [correction of
      biodisponibility] of niphedipine was double in the patients with hepatic
      cirrhosis versus the healthy subjects. The modified pharmacokinetics of
      niphedipine in the patients with hepatic cirrhosis and the great individual
      variations found, require a decrease of the dose in this category of patients and
      a surveillance of the clinical effect.

PMID- 1982193
TI  - [The adverse digestive effects of nonsteroidal anti-inflammatory agents. Current
      physiopathological and clinical aspects. I. The adverse effects on the digestive
      track].

PMID- 1982194
TI  - Fate and effects of toxic chemicals in large rivers and their estuaries.
      Proceedings of an international symposium. Quebec City, Canada, 10-14 October
      1988.

PMID- 1982195
TI  - [Chronic pain in cancer patients].
AB  - Cancer pain relief is a public health problem. A WHO method has been developed,
      which provides for drugs to be administered immediately if there is pain, to be
      given "by the clock" rather than "on demand" and to be increased from nonopioids
      to weak opioids and then to strong opioids until the patient is free from pain.

PMID- 1982196
TI  - Relationship of major histocompatibility complex class II genes to inhibitor
      antibody formation in hemophilia A.
AB  - Approximately 14% of transfused hemophiliacs develop an anti-factor VIII
      inhibitory antibody which specifically neutralizes factor VIII procoagulant
      activity. In this study an association of the major histocompatibility complex
      (MHC) with inhibitor antibody formation was evaluated by restriction fragment
      length polymorphism (RFLP) analysis using BamHI, EcoRI, HindIII, PstI, PvuII and
      TaqI digested genomic DNA probed with DP beta, DQ alpha, DQ beta and DR beta
      class II MHC gene probes. The RFLP patterns for 16 non-inhibitor and 11 inhibitor
      hemophiliac patients were analyzed. These 24 enzyme:probe combinations generated
      231 fragments. Fifteen (15) fragments associated with the inhibitor phenotype;
      odds ratios ranged from 5.1 to 45 and lower bounds of 95% confidence intervals
      were greater than 1.000 for all 15 fragments. Five (5) fragments associated with
      non-inhibitors, with odds ratios ranging from 6.4 to 51.7. This report
      establishes a MHC related genetic basis for the inhibitor phenotype. No
      statistically significant differences in the distribution of serologically
      defined HLA-DR phenotypes were observed between the inhibitor and non-inhibitor
      groups.

PMID- 1982197
TI  - [12th All-Union Congress of Roentgenologists and Radiologists (Radiodiagnosis)].

PMID- 1982198
TI  - [Sugar. Nutritive medical significance of sugar--current status. A symposium.
      Biebelried, 11-12 May 1990].

PMID- 1982199
TI  - Twin Biology. Proceedings of the Sixth International Congress on Twin Studies.
      Rome, 28-31 August 1989.

PMID- 1982200
TI  - Spinal neuronal pathology associated with continuous intrathecal infusion of N
      methyl-D-aspartate in the rat.
AB  - Continuous intrathecal infusion of N-methyl-D-aspartate (NMDA) at the level of
      the lumbar enlargement of the spinal cord in middle-aged rats produced dose
      dependent toxicity of spinal cord neuronal systems. Toxicity was enhanced by
      coadministration of glycine, but was significantly reduced when NMDA was co
      administered with the competitive inhibitor DL-2-amino-5-phosphovaleric acid or
      the noncompetitive inhibitor MgSO4. The toxic effects of NMDA were manifest most
      dramatically and at the lowest concentrations in the neuropil, while neuronal
      loss was obvious at higher concentrations. The distribution and intensity of
      reactive astrocytosis was consistent with the known regional and subcellular
      distribution of NMDA receptors in the spinal cord of rats. The increase in
      ribosomes and rough endoplasmic reticulum observed in anterior horn cells
      suggested an increase of cell metabolism reflecting either a nonspecific response
      to injury or a specific increase in cell metabolism secondary to sustained
      activation of NMDA receptors. The present studies implicate excitatory amino acid
      receptors of the NMDA type in producing toxicity to selected neuronal populations
      of the spinal cord. This model provides a system for studies of the protective
      effects and rescue of neuronal populations susceptible to the toxic effects of
      excitatory amino acids.

PMID- 1982201
TI  - The in vivo and in vitro activity of AHR-13268D, a new
      antiallergic/antihistaminic agent.
AB  - AHR-13268D (4-[3-[4-[Bis(4-fluorophenyl)hydroxymethyl]-1-
      piperidinyl]propoxy]benzoic acid, sodium salt) is a potent, long-acting water
      soluble, antiallergic and antihistaminic agent. AHR-13268D protects sensitive
      guinea pigs from collapse induced by aerosolized antigen; 1, 5, and 24 h ED50s in
      the test were 0.27, 0.25, 0.93 mg/kg, PO, respectively. AHR-13268D was also
      active when given as an aerosol, the 1 h ED50 = 0.29%. In the rat passivefoot
      anaphylaxis test. AHR-13268D was slightly more active (1.55 times) than AHR-5333B
      when given orally 1 h prior to challenge and equipotent to cromolyn when given
      intravenously immediately prior to challenge. AHR-13268D displayed potent, long
      acting antihistaminic activity in naive guinea pigs; the 1, 5, and 24 h oral
      ED50s being in the range of 0.3 mg/kg. AHR-13268D (10 to 20 mg/kg, PO) attenuated
      the skin responses to ascaris antigen in sensitive dogs and did not alter the EEG
      pattern or sleep/wake patterns of cats at doses in vast excess of its
      antihistaminic activity. In vitro, AHR-13268D was a potent inhibitor of histamine
      release from rat peritoneal mast cells (IC50 = 0.51 nM) and was as potent as the
      reference 5-LO inhibitor phenidone in inhibiting antigen-induced contractions of
      guinea pig ileum in the presence of pyrilamine, atropine, and imidazole (IC50
      approximately 300 microM). AHR-13268B was bioavailable (approximately 88%) from
      capsules or from oral solutions.

PMID- 1982202
TI  - Central cardiovascular responses of histamine and homodimaprit in normal and
      hypophysectomized rats.
AB  - Central administration of histamine in conscious rats produced half the pressor
      response in hypophysectomized rats compared to normal animals. The pressor
      response was blocked completely by hexamethonium in hypophysectomized rats but
      not at all in normal rats. Homodimaprit given centrally, gave pressor effects of
      equal magnitude in both groups. In normal rats, it caused significantly higher
      blood blood pressure following ganglionic blockade, whereas in hypophysectomized
      rats hexamethonium did not block the response to homodimaprit. These results,
      plus previous findings, show that histamine, given centrally, raises blood
      pressure in normal conscious animals by releasing vasoactive substances from the
      brain. In hypophysectomized rats it stimulates sympathetic output. Homodimaprit,
      on the other hand, produces its pressor action by the release of vasoactive
      substances from the brain both in normal and hypophysectomized animals. A
      hypothesis is proposed to suggest that parallel neuronal processing occurs in the
      brain when histamine is given.

PMID- 1982203
TI  - The clinical significance and management of calcific pulp obliteration.
AB  - In this paper, the biological events that give rise to the radiographic
      appearance called calcific pulp obliteration will be described, as will the
      anatomical and histological changes that attend its presence. There will also be
      a review of the studies that explore the relative incidence of this pulp change
      subsequent to trauma, and the incidence of attending periapical disease that
      should indicate to the clinician that some form of treatment is required.
      Finally, the endodontic management of these teeth will be described with emphasis
      on the types of adjustments that can be made to minimize the chance for a
      procedural accident.

PMID- 1982204
TI  - Metabolism of glutamine in erythrocytes infected with the human malaria parasite:
      Plasmodium falciparum.
AB  - The metabolism of glutamine was studied in erythrocytes infected with Plasmodium
      falciparum, comparatively to normal cells, in presence or not of DON (6-diazo-5
      oxo-L-norleucine) or acivicin, two glutamine antagonists which have been shown to
      inhibit the growth of P. falciparum in vitro. Extracellular glutamine was
      partially converted into glutamate using two routes corresponding to gamma
      glutamyl transpeptidase (GGT) and glutaminase activities. In cells infected with
      mature trophozoites, the observed enhancement of the glutamine influx and of the
      glutamate formation was consistent with the enhancement of GGT and glutaminase
      activities.

PMID- 1982205
TI  - Multiplication of the class I alcohol dehydrogenase locus in mammalian evolution.
AB  - Chromosomal DNA samples derived from various primates and other mammals (horse,
      sheep, rabbit, and mouse) were digested with restriction endonuclease and
      hybridized with a probe of the sixth exon of the human ADH gene, which is highly
      conserved in the class I alcohol dehydrogenase of these mammalian species. The
      copy number of the class I ADH gene in each species was estimated from the number
      of hybridized bands. Primate DNA samples showed three distinct bands in the blots
      of PstI digest and DraI digest. Moreover, most of the bands from primate DNA
      showed a similarity in size so as to allow us to assign the ADH1, ADH2, and ADH3
      homologues in each species. In contrast, mouse has only one gene, and rabbit,
      sheep, and horse seem to have only two genes, for the class I ADH, which showed
      divergent hybridization bands. These results are consistent with the view that
      the human class I ADH gene cluster has been generated through gene multiplication
      events which occurred before the Catarrhini branch point in the course of primate
      evolution.

PMID- 1982206
TI  - Restriction fragment length polymorphisms detected in N-ras-related sequences of
      rats and their linkage analyses.
AB  - Novel restriction fragment length polymorphisms (RFLPs) in inbred rats were
      revealed with the human N-ras gene as probe. Three fragments hybridizing to the
      probe were detected by Southern blot hybridization under highly stringent
      conditions, and one of the fragments showed variation in inbred rat strains.
      Furthermore, on hybridization under low-stringency conditions, an additional
      fragment hybridizing to the probe was observed, and this fragment also showed
      interstrain variation. These two variant fragments showed different distributions
      in 27 inbred rat strains and segregated in backcross progeny as codominant
      alleles of independent single autosomal loci. Therefore, the loci for these RFLPs
      were named Nras-1 and Nras-2, respectively. Analyses of linkages between the
      RFLPs and 11 other loci revealed that the Nras-2 locus was closely linked to the
      c locus (3.7 +/- 2.6%), which belongs to rat linkage group I.

PMID- 1982208
TI  - Cell type-specific enhancement in the Drosophila embryo by consensus homeodomain
      binding sites.

PMID- 1982207
TI  - Genetic diversity at an oncogene locus and in mitochondrial DNA between
      populations of cancer-prone Atlantic tomcod.
AB  - It has been reported that Atlantic tomcod (Microgadus tomcod) from the Hudson
      River exhibit an extremely high incidence of liver tumors. More than 90% of
      spawning 2-year-old fish display hepatocellular carcinomas. In contrast,
      representatives of this species from a relatively pristine environment show a
      much lower incidence of tumors. Genomic DNA and mitochondrial DNA (mtDNA) were
      isolated from tomcod from the Hudson River, New York, and the Saco River and
      Royal River, Maine. We found a statistically significant difference in the
      frequency of PstI-generated restriction fragment length polymorphisms in the abl
      cellular oncogene between Hudson and Maine tomcod. Allelic variation was observed
      at two of the three abl domains scored. A single composite genotype seen in
      approximately 40% of Hudson River fish was seen in only one Maine fish. This
      polymorphism enabled us to differentiate a Hudson River population from that
      encountered in the Maine rivers. This is the first demonstration of a population
      specific polymorphism at a cellular oncogene locus in any species. In contrast,
      no restriction site polymorphisms were seen in mtDNA between the populations. The
      lack of mtDNA diversity in these fish is consistent with the geological history
      of the area. In combination, these results suggest that the genetic diversity
      observed at the c-abl oncogene locus must have been a fairly recent event and
      that oncogene loci may be particularly sensitive to mutational change.

PMID- 1982209
TI  - Protection by pyroglutamic acid and some of its newly synthesized derivatives
      against glutamate-induced seizures in mice.
AB  - The protection by pyroglutamic acid (CAS 98-79-3) and derivatives Ia-i (injected
      i.p.) against glutamate- and NMDA (N-methyl-D-aspartate) (i.c.v.) induced
      seizures in mice has been studied in comparison with known antiepileptics and
      antagonists of excitatory aminoacids. The potency of pyroglutamic acid and some
      derivatives (Id,f,g,h) against glutamate-induced convulsions was similar to that
      shown by glutamic acid diethylester and by valproic acid. Interestingly,
      pyroglutamic acid did not affect NMDA-induced convulsions which were well
      antagonized by both 2-amino-5-phosphono valeric acid and by diazepam. Thus,
      pyroglutamic acid may represent the starting for synthesis of excitatory
      aminoacid antagonists acting at non NMDA receptors.

PMID- 1982210
TI  - Chronic intravenous toxicity of the new antibiotic cefpirome in monkeys.
AB  - Chronic intravenous toxicity studies in monkeys were carried out with 3-[(2,3
      cyclopenteno-1-pyridinium)-methyl]-7-[2-syn-methoximino - 2-(2-aminothiazol-4-yl)
      acetamido]-ceph-3-em-4-carboxylate (cefpirome, HR 810; CAS 84957-29-9) a new
      cephalosporin derivative. In a 90-day study in rhesus monkeys (4 males/4 females
      per group) dosages of 0, 50, 160 and 500 mg/kg/day were administered. In a 6
      month study 5 groups of 6 male and 6 female cynomolgus monkeys received NaCl
      solution (0.9%), the vehicle, and 50, 200 or 800/400 mg/kg/d (the highest dosage
      had to be lowered after the first week due to acute drug intolerance). For
      clarification of the dose relationship to the findings in the 800/400 mg/kg
      group, a supplementary 6-month study with 500 mg/kg cefpirome including a vehicle
      control was also performed. 50 mg cefpirome/kg/d was well tolerated; so too were
      160 and 200 mg/kg apart from a slight beta 2-microglobulinuria and/or enzymuria.
      Almost exclusively at the high dosages retching and vomiting, and exclusively at
      the high dosages diarrhea, inappetence and physical weakness were sporadically
      seen in the first phase of the studies. 500 and 400 mg/kg led to increasing signs
      of discrete renal tubular changes (enzymuria, beta 2-microglobulinuria,
      cylindruria and minimal histological changes in 2 animals of the 400 mg/kg
      group). In one rhesus monkey (500 mg/kg) and two cynomolgus monkeys (800 mg/kg)
      severe kidney damage had developed within the first week. In all dosage groups of
      the 90-day study special histological methods revealed a dose-dependent increase
      and enlargement of lysosomes in the epithelia of the proximal renal tubules.
      Increased cytolysis was, however, not observed. In all the studies there was a
      dose-dependent increase in the kidney weights of the intermediate and highest
      dosage groups. The females of the 400 mg/kg group showed slight anemia
      accompanied by a slight increase in the reticulocyte count. One animal of this
      group died prematurely probably due to pulmonary embolism. The signs of slight
      renal impairment including lysosome enlargement, and the slight anemia proved to
      be reversible.

PMID- 1982212
TI  - The degradation of bioactive peptides and proteins by dipeptidyl peptidase IV
      from human placenta.
AB  - The degradation of several bioactive peptides and proteins by purified human
      dipeptidyl peptidase IV is reported. It was hitherto unknown that human gastrin
      releasing peptide, human chorionic gonadotropin, human pancreatic polypeptide,
      sheep prolactin, aprotinin, corticotropin-like intermediate lobe peptide and (Tyr
      )melanostatin are substrates of this peptidase. Kinetic constants were determined
      for the degradation of a number of other natural peptides, including substance P,
      the degradation of which has been described earlier in a qualitative manner.
      Generally, small peptides are degraded much more rapidly than proteins. However,
      the Km-values seem to be independent of the peptide chain length. The influence
      of the action of dipeptidyl peptidase IV on the biological function of peptides
      and proteins is discussed.

PMID- 1982211
TI  - Type of fimbriation determines adherence of Klebsiella bacteria to human
      epithelial cells.
AB  - Clinical isolates of three Klebsiella strains (encapsulated and nonencapsulated
      mutants) with type 1 (mannose-sensitive, MS+MR-), type 3 (mannose-resistant, MS
      MR+) and type 1 and 3 (MS+MR+) fimbriae were investigated for their ability to
      adhere to epithelial cells. Considerable adhesion to human buccal, tracheal,
      pulmonary and uroepithelial cells could be demonstrated. Independent of
      encapsulation and type of epithelial cells, adhesion of MS+MR+ (type 1.3)
      fimbriated Klebsiella bacteria was significantly stronger than adhesion of
      microorganisms carrying only type 1 (MS+MR-) or type 3 (MS-MR+) fimbriate,
      respectively. Adherence of nonencapsulated type 1 and 3 (MS+MR+) fimbriated
      Klebsiella bacteria to mammalian cells was significantly inhibited in the
      presence of D-mannose. Certain carbohydrates (D-glucose, D-galactose) did not
      interfere with this adhesion process.

PMID- 1982213
TI  - Microtubules, mitochondria, and molecular chaperones: a new hypothesis for in
      vivo assembly of microtubules.
AB  - In Chinese hamster ovary cells, a number of independent mutants selected for
      resistance to antimitotic drugs have been found to be specifically altered in two
      major cellular proteins, designated P1 (relative mass (Mr) approximately 60-63
      kilodaltons (kDa] and P2 (Mr approximately 69-70 kDa), which appeared microtubule
      related by a number of genetic and biochemical criteria. Antibodies to P1 have
      been found to bind specifically to mitochondria that showed specific association
      with microtubules in interphase cells. Biochemical and cDNA sequence studies on
      P1 showed that this protein, which is localized in the matrix compartment, is the
      mammalian homolog of the highly conserved chaperonin family of proteins (other
      members include the GroEL protein of Escherichia coli, the 60-kDa heat-shock
      protein of yeast, and the rubisco subunit binding protein of plant chloroplasts).
      The chaperonin proteins in various systems play a transient but essential
      molecular chaperone role in the proper folding of polypeptide chains and their
      assembly into oligomeric protein complexes. Our studies on P2 protein established
      that it corresponds to the constitutive form of the major 70-kDa heat-shock
      protein of mammalian cells (i.e., hsc70), which also acts as a molecular
      chaperone in the intracellular transport of nascent proteins to organelles such
      as mitochondria and endoplasmic reticulum. To account for the above, as well as a
      number of other observations (e.g., binding of fluorescent-labeled antimitotic
      drugs to mitochondria, association of tubulin with mitochondria as well as other
      membranes, and high affinity binding of antimitotic drugs to free tubulin but not
      to assembled microtubules), a new model for the in vivo assembly of interphase
      microtubules is proposed. The model ascribes a central role to the
      mitochondrially localized chaperonin (i.e., P1) protein in the intracellular
      formation of tubulin dimers and in their addition to the growth sites in
      microtubules. The proposed model also explains a number of other observations
      related to microtubule assembly in the literature.

PMID- 1982214
TI  - Inhibitors of chymotrypsin-like activities selectively block the mitotic pathway
      in rat hepatoma cells.
AB  - We provide evidence that both covalent and non-covalent inhibitors of
      chymotrypsin-like activities inhibit the insulin-induced DNA replication, while
      the hormonal metabolic effects such as induction of tyrosine aminotransferase
      activity or increase of amino-acid transport remain unchanged. Besides, the
      protease inhibitors that we tested were without any effect on both the
      autocatalytic phosphorylation of insulin receptors and the tyrosine kinase
      activity towards poly(glutamate/tyrosine). The inhibitory effect of protease
      inhibitors on DNA synthesis was also visible when fibroblast growth factor (FGF)
      was used to commit cells in the proliferative cycle. This observation proves that
      the involvement of a putative protease is not restricted to the insulin mitogenic
      pathway. Finally, we observed that Fao cells totally escaped the inhibitory
      action of a covalent inhibitor of chymotrypsin after having been exposed to
      insulin for 10 h. We propose that a chymotrypsin-like activity is involved in the
      intracellular signalling leading to the proliferation of rat hepatoma cells up to
      a non-return point situated in the middle of G1 (6-8 h).

PMID- 1982215
TI  - Regulation of the multidrug resistance gene in regenerating rat liver.
AB  - The MDR1 gene encodes an Mr 170,000 energy-dependent drug efflux pump (P
      glycoprotein) which transports hydrophobic agents such as Adriamycin, colchicine,
      the Vinca alkaloids, and actinomycin D out of cells. Increased expression of the
      mdr gene has been observed in preneoplastic and neoplastic carcinogen-induced rat
      liver nodules as well as in regenerating rat liver, suggesting that the mdr gene
      is regulated in response to liver injury. To determine whether the increased
      levels of mdr mRNA seen in regenerating liver are the result of an increased rate
      of transcription or a posttranscriptional event, nuclear run-on assays were
      performed on nuclei isolated from regenerating rat livers 4-72 h after partial
      hepatectomy. Whereas Northern blot analysis of regenerating rat liver
      demonstrated a greater than 20-fold increase in mdr mRNA levels, there was little
      or no increase in mdr gene transcription as measured by nuclear run-on analyses.
      beta-Actin and metallothionein gene transcription levels, known to increase
      transiently in regenerating liver, both showed increased nuclear run-on activity
      4 h posthepatectomy, indicating that the nuclei were functional. Failure to
      demonstrate a substantial increase in mdr gene transcription suggests that the
      observed increase in mdr mRNA levels may result from a posttranscriptional event
      such as message stabilization. The sequence of the 3' noncoding region of the
      MDR1 gene shares strong homology with other unstable mRNAs, suggesting that RNA
      stabilization could account for the rise of mdr mRNA after partial hepatectomy.

PMID- 1982216
TI  - Contribution of quisqualate/kainate and NMDA receptors to excitatory synaptic
      transmission in the rat's visual cortex.
AB  - Action of antagonists for excitatory amino-acid (EAA) receptors on
      extracellularly and intracellularly recorded responses of layer II/III cels to
      electrical stimulation of the underlying white matter were studied in a slice
      preparation of rat's visual cortex. Antagonists used were 2-amino-5
      phosphonovalerate (APV) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), which
      are selective antagonists for EAA receptors of N-methyl-D-aspartate (NMDA) and
      quisqualate/kainate (non-NMDA) type, respectively. In extracellular recordings,
      it was found that responses of almost all of the cells were suppressed by CNQX.
      In contrast, sensitivity to APV was different between cells with short-and long
      latency responses; 81% of the former responses were not suppressed by APV, while
      about a half of the latter were suppressed. Excitatory postsynaptic potentials
      (EPSPs) evoked by white-matter stimulation were recorded intracellularly from 42
      neurons. Most of polysynaptically elicited EPSPs were sensitive to AVP, whereas
      the majority of monosynaptic EPSPs, were not. CNQX almost completely suppressed
      EPSPs irrespective of monosynaptically or polysynaptically evoked, but in some
      cases slow EPSPs with low amplitude were spared. These CNQX-resistant EPSPs were
      elicited polysynaptically and had an anomalous voltage dependence, a
      characteristic of NMDA receptors. It is suggested that non-NMDA receptors
      contribute dominantly to first-order synaptic transmission while NMDA receptors
      participate substantially in second-order transmission so as to serve as a
      booster of outputs from visual cortex.

PMID- 1982217
TI  - [Neonatal brain-derived carcinostatic factor (NBCF)--cytocidal action to
      neuroblastoma cells and molecular characters as a glycoprotein].
AB  - Neuronal cells as many as 40-70% in several regions of the brain are destined to
      suffer from programmed cell death at the terminal stage of the ontogenesis. At
      the stage the mouse brain secretes some species of cell growth-inhibitory factors
      including a novel glycoprotein (62KD, pI9.1) which inhibits DNA synthesis and
      proliferation of tumor cells preferentially over those of normal cells. The
      factor was designated as NBCF (neonatal brain-derived carcinostatic factor)
      because it is not produced at stages other than neonatal and prenatal stages or
      from other organs. The activity is exhibited through a protenic body of NBCF as
      an active principle, whereas the glycan moiety contributes assumedly to secretion
      and/or activity stabilization. NBCF is cytocidal more markedly to neuroblastoma
      cells than a diversity of other tumor cells; the susceptibility to NBCF becomes
      marked when neuroblastoma cells are undifferentiated.

PMID- 1982218
TI  - The role of monocytes in IL-3 enhancement of human T cell proliferation.
AB  - We have assessed the role of recombinant human interleukin 3 (rIL-3) in the
      activation and proliferation of peripheral blood lymphocytes (PBL) and their
      various subsets. rIL-3 significantly enhanced the CD2-responsiveness of
      unfractionated PBL. Proliferating cells were mainly T lymphocytes and most of
      them expressed CD4. This effect was absent following adherent cell depletion from
      PBL. rIL-3 also failed to directly activate purified lymphocytes, nor did it
      increase T cell responsiveness to mitogens and/or IL-2. By contrast, rIL-3
      induced monocyte functions as enhancement of IL-1 production was observed
      following treatment of these cells by rIL-3. This effect was removed by anti IL-3
      mAb addition to these cultures. In addition, anti IL-1 antibody partially
      inhibits IL-3-derived responses. Together, these data strongly suggest that IL-3
      stimulation of T lymphocytes is related mainly to its ability to enhance monocyte
      functions.

PMID- 1982219
TI  - Immunoregulatory functions of paf-acether. VI. Inhibition of T cell activation
      via CD3 and potentiation of T cell activation via CD2.
AB  - In the present report we further explored the role of paf-acether (paf), a
      phospholipid cytokine, in the modulation of T cell activation induced via the CD2
      and the CD3 pathways. Evidence was obtained that paf inhibited T cell
      proliferation induced by immobilized CD3 mAb (OKT3i), but potentiated that
      induced by a combination with the CD2 mAb, anti-(T11.1 + D66). Both effects were
      dose-dependent between 2 and 10 microM paf, and specific in that lysoPC, a
      phospholipid closely related to paf, had no effect. The inhibition became
      apparent after 48 h and was maintained up to 144 h of culture, whereas the
      enhancement was observed only by 96 h of culture. Interestingly, paf was able to
      inhibit OKT3i mAb response when added to cultures as late as 24-48 h after the
      initiation of a 96 h incubation. By contrast, paf enhanced the proliferative
      response only when added concomitantly with anti-(T11.1 + D66) mAb, suggesting
      that it modulates an early event of T cell activation. paf, which enhanced T cell
      proliferation induced via the CD2 pathway, also led to a substantial up
      regulation of IL-2 secretion and CD25 expression. Moreover, paf markedly
      augmented IL-4 secretion upon CD2 mAb stimulation. Finally, when T cells were
      triggered via the CD3 molecule, paf inhibited the proliferative response but also
      down-modulated CD25 expression without impairing IL-2 secretion. When considered
      together, these data demonstrate that paf, a phospholipid cytokine released
      during inflammatory reactions, play a differential regulatory role in T cell
      activation induced via the CD3 and CD2 (T11.1 + D66) pathways.

PMID- 1982220
TI  - Molecular cloning of cDNA encoding MS2 antigen, a novel cell surface antigen
      strongly expressed in murine monocytic lineage.
AB  - cDNA clones which strongly hybridized with a 3.1 kb mRNA from mouse macrophages
      and macrophage cell lines and weakly with mRNA from P815 but not from a variety
      of other cell lines and tissues were isolated from cDNA libraries constructed
      using mRNA from murine macrophage cell lines and peritoneal macrophages.
      Treatment of a macrophage cell line with macrophage stimulators significantly
      enhanced transcription of the mRNA. Sequencing analysis of these clones
      demonstrated that the cDNA consisted of 3036 bp insert containing a 2478 bp open
      reading frame followed by a 538 bp 3' untranslated region. The amino acid
      sequence, deduced from the nucleotide sequence of the cDNA, predicted a protein
      containing a signal peptide, an extracellular region, a transmembrane domain, and
      a cytoplasmic tail. The extracellular region had five putative N-glycosylation
      sites and a cysteine-rich domain, whereas the cytoplasmic region consisted of a
      proline-rich amino acid sequence significantly similar to CD2. SDS-PAGE and
      NEPHGE SDS-PAGE analysis of the immunoprecipitated membrane of the macrophage
      cell lines prepared by using rabbit anti-MS2 peptide antibody raised against a
      synthetic peptide preparation relative to a hydrophilic region of the MS2 amino
      acid sequence confirmed that MS2 protein is a cross-linked protein having
      approximate molecular sizes of 89 kd and pl 6.5-7.0. These results show that MS2
      protein is a novel cell surface antigen expressed mainly in monocytic lineages.

PMID- 1982221
TI  - Alteration of human epidermal transglutaminase during its activation.
AB  - The effects of enhancement of enzymatic activity by heating at 56 degrees C or by
      limited treatment with dimethylsulfoxide, trypsin and cathepsin D on two forms
      (Mr = 50 kDa and 72 kDa) of human epidermal transglutaminase were studied by
      immunoblots using rabbit antihuman epidermal transglutaminase. Both 50 kDa and 72
      kDa transglutaminase bands were detected without any alteration in the mobility
      of the transglutaminase bands during activation induced by heating at 56 degrees
      C or by pretreatment with dimethylsulfoxide. With a preincubation period longer
      than 60 min, the trypsin pretreated sample showed progressive disappearance of
      the 72 kDa transglutaminase band in conjunction with the loss of transglutaminase
      activity. On the other hand, samples preincubated with cathepsin D showed a
      complete disappearance of the 50 kDa band after 180 min. These studies suggest
      the different forms of human epidermal transglutaminase may regulate enzyme
      activity each other during normal epidermal differentiation.

PMID- 1982222
TI  - What determines the time course of neurotransmitter release in fast synapses?

PMID- 1982223
TI  - Mediators of vasogenic brain edema.

PMID- 1982224
TI  - Modulation of glutamate effects by GABA in neocortical and archicortical
      structures.

PMID- 1982225
TI  - Excitation of brain stem neurons by noradrenaline and histamine.

PMID- 1982226
TI  - Heat shock proteins induce pores in membranes.
AB  - Human heat shock protein (hsp) 70 and bacterial protein groEL promote leakage of
      calcein from liposomes induced by human serum albumin signal peptide, by S.
      aureus alpha toxin or by diphtheria toxin. Hsp 70 and groEL, as well as two
      mycobacterial homologues hsp 71 and hsp 65, induce ion conducting pores across
      planar lipid bilayers at low or neutral pH. It is concluded that hsp induce pores
      in membranes and that this may contribute to their action within cells.

PMID- 1982227
TI  - Cationic and anionic amino acid transport studies in rat red blood cells.
AB  - The transport of L-proline, L-lysine and L-glutamate in rat red blood cells has
      been studied. L-proline and L-lysine uptake were Na(+)-independent. When the
      concentration dependence was studied both showed a non-saturable uptake
      assimilable to a difussion-like process, with high Kd values (0.718 and 0.191 min
      1 for L-proline and L-lysine respectively). Rat red blood cells showed high
      impermeability to L-glutamate. No sodium dependence was observed and the Kd value
      was low (0.067 min-1). Our results show firstly, that rat red blood cells do not
      have amino acid transport systems for anionic and cationic amino acids and
      secondly that erythrocytes show no sodium-dependent L-proline transport, and that
      these cells are very permeable to this amino acid.

PMID- 1982228
TI  - Autologous bone marrow transplantation for acute myeloid leukemia following in
      vitro treatment with neuraminidase and monoclonal antibodies.
AB  - Although monoclonal antibodies (MoAbs) to CD15, especially PM-81, react with
      leukemic blasts from the majority of patients with acute myeloid leukemia (AML),
      a small subset of patients have cells that are CD15 negative or dim. We
      determined previously that neuraminidase will increase the reactivity of PM-81
      with AML blasts, as well as blasts from many patients with acute lymphoblastic
      leukemia (ALL). In this report, we describe the laboratory results and clinical
      course of the first patient with AML whose harvested bone marrow was treated with
      neuraminidase prior to MoAbs and complement treatment. Neuraminidase increased
      the percentage of the patient's leukemia cells that reacted with PM-81 from 18%
      to 90% and more than doubled the percentage of AML blasts that were lysed by PM
      81 and complement. The patient suffered no acute toxicity, engrafted rapidly, and
      was transfusion independent by day 21 post-ABMT. This report demonstrates the
      probable safety and efficacy of pretreatment of bone marrow with neuraminidase,
      and increases the number of patients with AML or ALL who may benefit from ABMT
      using marrow purging with MoAb to CD15.

PMID- 1982229
TI  - Effects of hypomagnesia on transmitter actions in neocortical slices.
AB  - 1. The effects of hypomagnesia on the neuronal responses induced by
      iontophorectically applied acetylcholine, glutamate, N-methylaspartate (NMDA) and
      gamma-aminobutyric acid (GABA) were investigated using intracellular recording
      techniques in in vitro slices of sensorimotor cortex (guinea-pigs). 2. Perfusion
      with Mg-free media, with or without tetrodotoxin (TTX), induced a small
      hyperpolarization (approximately 4 mV) and a small decrease (approximately 10%)
      in the input resistance of neurones. During TTX-blockade of Na-spike genesis,
      spontaneous depolarizing waves of low frequencies were observed in neurones of
      slices under Mg-free conditions. 3. The effects of acetylcholine and to a lesser
      extent, GABA actions, were depressed in a dose-dependent, reversible manner by
      decreases in the [Mg2+] of the perfusing media. In neurones of slices that had
      been incubated in Mg-free artificial cerebrospinal fluid to ensure a maximal
      depletion, the responses to these transmitters were potentiated by each
      sequentially administered increase in extracellular [Mg2+]. The actions of NMDA
      were potentiated during perfusion of Mg-free media. However, the responses to
      glutamate, which may activate receptors for NMDA, were either depressed or
      unchanged under these conditions. 4. A regulatory role for external Mg cations in
      the responses of neocortical neurones to the transmitter substances,
      acetylcholine and GABA, can be inferred from these investigations which simulate
      hypomagnesemia. The dose-dependent depression of GABA actions by low
      extracellular [Mg2+] additionally provides a plausible mechanism that may
      contribute to the neuronal hyperexcitability that is observed during conditions
      of hypomagnesemia.

PMID- 1982230
TI  - Receptors involved in mechanical responses to catecholamines in the circular
      muscle of guinea-pig stomach treated with meclofenamate.
AB  - 1. In circular muscle strips of the fundus and corpus of guinea-pig stomach,
      mechanical responses to catecholamines were studied mainly in the presence of a
      prostaglandin biosynthesis inhibitor, meclofenamate. 2. Normal preparations
      developed considerable muscle tone, and adrenaline (10-100 microM) in the
      presence of 3-5 microM propranolol produced a multiphasic response, generally
      consisting of transient relaxation and contraction, followed by slow relaxation
      and then contraction. Responses to phenylephrine were similar to those of
      adrenaline. 3. Meclofenamate (0.3 microM) nearly abolished the muscle tone and
      under this condition, both adrenaline and phenylephrine produced a simple
      contraction. This response was strongly inhibited by prazosin, but only weakly by
      yohimbine. 4. When muscle tone was maintained by prostaglandin E2 (10 nM) in the
      presence of meclofenamate, phenylephrine (30 microM) produced transient
      relaxation followed by slow contraction in most preparations. These were strongly
      inhibited by prazosin. Adrenaline produced a similar response, but the relaxation
      was only partially reduced by prazosin. The remaining relaxation was more
      dominant in the middle fundic region and this was considered to be mediated
      through beta-adrenoceptors. 5. It is concluded that in the circular muscle of the
      fundic region of guinea-pig stomach, endogenous prostaglandins are involved in
      maintaining muscle tone and in modifying the response to catecholamines and that
      both contraction and relaxation are mediated by alpha 1-adrenoceptors.

PMID- 1982231
TI  - Effects of putative neurotransmitters and related drugs on withdrawal
      contractures of guinea-pig isolated ileum following brief contact with
      [Met5]enkephalin.
AB  - 1. Brief exposure for 2 min of guinea-pig isolated ileum to [Met5]enkephalin
      (MEnk) and noradrenaline has been shown previously to produce withdrawal
      contractures on washout of the agonist or addition of naloxone (MEnk) or
      phentolamine (noradrenaline). 2. The present study was undertaken to investigate
      firstly, whether other putative neurotransmitters and/or related drugs which
      inhibit transmitter release also produced withdrawal responses following 2 min
      contact with the ileum and secondly, whether they affected the opioid withdrawal
      response. 3. Adenosine (1-5 microM), but not U-50,488H (1-5 microM), somatostatin
      (0.01-5 microM), ocreotide (1-5 microM), baclofen (1-25 microM) or dopamine (5,
      50 microM), produced a contracture on washout following 2 min contact with the
      ileum. The adenosine (5 microM) washout contracture, in common with MEnk and
      noradrenaline washout contractures, was inhibited by the substance P antagonist,
      spantide (10 microM). 4. Added 30 s before washout at a concentration of 5
      microM, noradrenaline, U-50,488H, adenosine, somatostatin and ocreotide
      significantly inhibited the washout withdrawal response following 2 min contact
      of the ileum with MEnk, 1 microM. A higher concentration of baclofen, 250 microM,
      also inhibited this response. 5. The naloxone (1 microM)-precipitated withdrawal
      response following contact of the ileum with MEnk, 1 microM, for 2 min, was
      inhibited only by noradrenaline (5 microM) and U-50,488H (5 microM). 6. It is
      concluded that during naloxone-precipitated opioid withdrawal an additional
      population of enteric motor neurones is recruited which is not involved in the
      washout withdrawal response and these neurones have less diversity of presynaptic
      receptors mediating inhibition of transmitter release than cholinergic motor
      neurones.

PMID- 1982233
TI  - Rhythmic bursting patterns induced in neurons of the rat nucleus tractus
      solitarii, in vitro, in response to N-methyl-D-aspartate.
AB  - The activity of nucleus tractus solitarii (NTS) neurons was recorded
      extracellularly on rat brainstem slices. Depending on the neuron, bath
      application of N-methyl-D-aspartate (NMDA; 30-120 microM) elicited either a
      pattern of rhythmic bursting or repetitive firing. The rhythmic bursting pattern
      was characterized by trains of action potentials occurring at a rate of 0.36-2
      Hz. With most of the neurons, the mean burst duration and the mean discharge
      frequency ranged between 200 and 800 ms and between 20 and 40 Hz, respectively.
      Both the repetitive and the rhythmic bursting patterns were reversibly blocked
      when DL-2-amino-5-phosphonovalerate (80 microM) was applied. Application of
      quisqualate (30-60 microM) or glutamate (300-1200 microM) on NTS neurons induced
      only repetitive firing even in neurons exhibiting a rhythmic bursting pattern
      under NMDA. The present findings show that rhythmic bursting patterns can be
      generated within the isolated NTS under activation of NMDA receptors. The
      rhythmic bursting resulted probably from local NTS mechanisms (synaptic
      interactions or neuronal intrinsic properties) which might be involved in
      physiological rhythmic activities organized at the NTS level, such as swallowing.

PMID- 1982232
TI  - Functional characterization of neuronal pre and postsynaptic alpha 2-adrenoceptor
      subtypes in guinea-pig submucosal plexus.
AB  - 1. The alpha 2-adrenoceptors on cell bodies of submucosal neurones, on
      presynaptic cholinergic nerve terminals innervating submucosal neurones, and on
      presynaptic sympathetic fibres innervating submucosal arterioles were
      characterized in functional studies by use of subtype selective ligands. 2. Both
      membrane hyperpolarization and presynaptic inhibition of nicotinic excitatory
      synaptic potentials (e.p.s.ps) produced by UK 14304 were similarly antagonized by
      idazoxan, yohimbine. SKF 104078, WB 4101 and ARC-239. Antagonism was competitive
      and dissociation equilibrium constants were the same for both effects. 3.
      Vasoconstriction of submucosal arterioles in response to stimulation of the
      sympathetic nerves (20 Hz for 2 s) was inhibited by UK 14304 and clonidine:
      concentrations producing half-maximum responses were 6 nm and 10 nM respectively.
      Idazoxan, yohimbine, WB 4101 and SKF 104078 antagonized this action, with
      dissociation constants similar to those for antagonism of the postsynaptic
      membrane hyperpolarization and presynaptic inhibition of nicotinic e.p.s.ps. 4.
      Oxymetazoline was a partial agonist when membrane hyperpolarization or
      presynaptic inhibition of nicotinic e.p.s.ps were measured but a full agonist
      when presynaptic inhibition of sympathetically-mediated arteriolar
      vasoconstriction was measured. As an agonist, oxymetazoline produced half maximum
      responses at 80-120 nM; the dissociation constant for oxymetazoline as an
      antagonist was 130 nM. 5. Neither prazosin nor chlorpromazine (up to 30 microM)
      altered any of the three responses to alpha 2-adrenoceptor agonists. 6. It is
      concluded that alpha 2-adrenoceptors present on submucosal neuronal cell bodies,
      on presynaptic cholinergic nerve terminals and on presynaptic sympathetic nerve
      terminals are the alpha 2A subtype. However, functional characterization of this
      subtype differs from that provided by ligand binding studies.

PMID- 1982234
TI  - Selective unilateral inactivation of striatal D1 and D2 dopamine receptor
      subtypes by EEDQ: turning behavior elicited by D2 dopamine receptor agonists.
AB  - The unilateral intrastriatal injection of the irreversible dopamine (DA) receptor
      blocker N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) induces a marked
      decrease in the density of D1 (-48%) and D2 (-51%) DA receptors available for
      binding to [3H]SCH 23390 and [3H]raclopride, respectively. A challenge dose of
      the D2 agonist LY 171555 (1 mg/kg, i.p., 24 h after EEDQ) causes intensive
      ipsiversive circling behavior, whereas the selective D1 agonist SKF 38393 (20
      mg/kg, i.p., 24 h after EEDQ) is unable to induce rotations. The density of D1
      and D2 DA receptors returns to basal levels by 7 days after the intrastriatal
      infusion of EEDQ. This biochemical recovery is associated with a progressive
      decrease in the number of rotations elicited by a challenge dose of LY 171555,
      suggesting that EEDQ does not cause any relevant neuronal damage. A selective
      inactivation of striatal D1 or D2 DA receptors can be obtained by injecting EEDQ
      30 min after the administration of the D2 antagonist raclopride (20 mg/kg, i.p.)
      or of the D1 antagonist SCH 23390 (2 mg/kg, s.c.), respectively. The intensity of
      the circling behavior induced by LY 171555 24 h after EEDQ in animals with a
      selective inactivation of D2 DA receptors is similar to that found in rats in
      which both D1 and D2 DA receptors have been inactivated. In contrast, LY 171555
      does not cause rotations when the density of D1 DA receptors is selectively
      decreased by EEDQ in rats pretreated with raclopride.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1982235
TI  - Tetanus during a high extracellular calcium pulse overrides the block of long
      term potentiation seen at 20 degrees C in the hamster hippocampal slice.
AB  - Extracellular CA1 pyramidal cell activity was measured at different temperatures
      in hamster hippocampal slices with bath Ca2+ concentration set at either 2.0 mM
      or 4.5 mM. Records taken before and after tetanic stimulation of Schaffer
      collateral/commissural pathways were compared to determine if long-term
      potentiation (LTP) developed. LTP, which cannot be elicited at 20 degrees C with
      2.0 mM calcium in the bath, was elicited at 20 degrees C when a tetanus was
      administered during a high calcium (4.5 mM) pulse. This LTP was limited to the
      tetanized pathway and was blocked by APV. Moreover, to elicit LTP at 20 degrees
      C, high (4.5 mM) extracellular calcium was needed both during and for several
      minutes following the tetanus. We conclude that mechanisms responsible for a
      thermal block of LTP are sensitive to calcium and that the thermal block can be
      overcome by increasing the amount of calcium that enters a cell during a tetanus.

PMID- 1982236
TI  - Involvement of a protein kinase C-dependent process in long-term potentiation
      formation in guinea pig superior colliculus slices.
AB  - Superior colliculus (SC) slices were prepared from guinea pig. Electrical
      stimulation was applied to the optic layer (OL) of the SC slices and the
      postsynaptic potential (PSP) was evoked in the superficial grey layer (SGL) of
      the SC. Tetanic stimulation to the OL evoked long-term potentiation (LTP) in the
      PSP. To investigate the involvement of the protein kinase C (PKC) system on the
      LTP formation in the SC, the effects of PKC activator (phorbol ester) and PKC
      inhibitors (polymyxin B, melittin and H-7) on the LTP formation have been
      studied. Application of phorbol ester to the medium at concentrations between 10(
      8) and 10(-10) M increased the amplitude of the PSP. On the other hand, the
      presence of phorbol ester at a concentration of 10(-6) M increased the glutamate
      release from the SGL slices. Tetanic stimulation which could not induce LTP by
      itself could elicit LTP during application of phorbol esters at the low
      concentration (3 X 10(-12) M). PKC inhibitors such as polymyxin B (10(-7) M),
      melittin (10(-8) M) and H-7 (10(-4) M) prevented LTP formation. When H-7 was
      applied once after LTP was formed, the enhanced PSP reduced to the original
      level. These results strongly indicate the involvement of PKC system on the LTP
      formation in the SC slices.

PMID- 1982237
TI  - Protection by ethanol of cortical neurons from N-methyl-D-aspartate-induced
      neurotoxicity is associated with blocking calcium influx.
AB  - Effect of ethanol on N-methyl-D-aspartate (NMDA)-induced neurotoxicity in rat
      dissociated cortical cells (8-12 day cultures) was studied. Treatment of cells
      with NMDA (50 and 500 microM) for 15 min caused cytotoxic effects on the cells,
      as examined by microscopic observations and lactate dehydrogenase release from
      cells 18 h after the treatment. Ca2+ is essential for these effects in medium
      during treatment. Presence of ethanol (50-300 mM) simultaneously with NMDA
      protected cells from the cytotoxicity depending on the concentration of ethanol.
      Calcium accumulation in cells on addition of NMDA, as monitored by fluorescence
      ratio (F405/F485) of Indo-1-preloaded cortical cells, was also decreased
      depending on the concentration of added ethanol. APV (200 microM) and ketamine
      (100 microM) blocked both the cytotoxicity and cellular calcium accumulation due
      to NMDA. These results suggest that ethanol effects its protection of neurons
      from NMDA-induced cytotoxicity by blocking the receptor-mediated calcium influx.

PMID- 1982238
TI  - Septohippocampal cholinergic pathway and penile erections induced by dopaminergic
      and cholinergic stimulants.
AB  - Penile erection was studied in rats injected with pilocarpine, amantadine and
      apomorphine. Pilocarpine and apomorphine are direct stimulants of muscarinic and
      dopaminergic receptors, respectively, while amantadine is reported to be an
      indirect stimulant of dopaminergic nerves. Single intraperitoneal injection of
      pilocarpine (0.1-3.2 mg/kg), amantadine (1-32 mg/kg) and apomorphine (0.01-1
      mg/kg) increased the number of penile erections with bell-shaped dose-response
      curves. The penile erections, irrespective of the stimulant used, were
      antagonized by doses (0.032-1 mg/kg) of scopolamine but not by those of
      methylscopolamine. Sulpiride treatment (1-32 mg/kg) had little effect on
      pilocarpine-induced penile erection while it attenuated dose-dependently the
      apomorphine- and amantadine-induced ones. Medial septum and fimbria-fornix
      lesions abolished penile erections by amantadine and apomorphine but not by
      pilocarpine. The similar results with amantadine and apomorphine suggest that the
      drugs activate postsynaptic dopamine receptors, which indirectly activate the
      septohippocampal cholinergic pathway to induce penile erections. Possible linkage
      between dopaminergic and cholinergic nerves is discussed.

PMID- 1982239
TI  - Stimulation of the hypothalamic paraventricular nucleus produces analgesia not
      mediated by vasopressin or endogenous opioids.
AB  - The analgesic effect of electrical stimulation of the hypothalamic
      paraventricular nucleus (PVN) was studied. Additionally, the involvement of
      vasopressin and opioid peptides in this process was examined by comparing
      vasopressin-deficient (Brattleboro) and Long-Evans rats and by administering the
      opiate antagonist naloxone. Rats were chronically implanted with a stimulating
      electrode in the parvocellular (PVN-Pc) and magnocellular (PVN-Mg) divisions of
      the PVN. At least 10 days after surgery, the analgesic effects of PVN stimulation
      were examined in lightly anesthetized rats, using the tail-flick method, and in
      unanesthetized rats, using the hot-plate test. PVN stimulation produced marked
      analgesia in both tests. Current threshold for analgesia was lower from PVN-Pc
      than from PVN-Mg. Threshold did not differ significantly between Brattleboro and
      Long-Evans rats and was not affected by naloxone administration. The results
      indicate that the PVN is part of the brain's pain inhibitory system, and show
      that the analgesia induced by PVN stimulation is not mediated by either
      vasopressin or opioid peptides.

PMID- 1982240
TI  - Evidence for clonidine presynaptically modulating amino acid release in the
      rostral ventral medulla: role in hypertension.
AB  - Reports suggested that the predominant site of action for the antihypertensive
      effects of clonidine is the rostral ventrolateral medulla (RVL), the presumed
      tonic vasomotor center. This study examined whether clonidine directly interacts
      with nerve terminal alpha 2-adrenergic receptors in the RVL to inhibit the
      release of sympathoexcitatory transmitters like glutamate (Glu) and aspartate
      (Asp), and/or facilitate the release of sympathoinhibitory transmitters like
      gamma-aminobutyric acid (GABA). Release of GABA and Glu was measured from
      synaptosomes prepared from the rostral ventral medulla of spontaneously
      hypertensive rats (SHR), a genetic model of hypertension, and normotensive Wistar
      Kyoto rats (WKY). Quantification of neurotransmitter release was performed by
      high-performance liquid chromatography. Depolarization with 35 mM K+
      significantly increased by 58-110% the release of GABA, Glu and Asp; however, no
      strain differences were observed. In contrast, spontaneous release of GABA and
      Asp was significantly lower in SHR than that of WKY (-36 and -41%, respectively);
      this effect was not observed for Glu. Clonidine (1 and 10 microM) enhanced the
      spontaneous release of GABA (+44%), Asp (+50%) and Glu (+70%) in SHR, but not
      WKY; this effect was prevented by yohimbine (1 microM). These data, together with
      previous findings, support the presence of facilitory alpha 2-adrenergic
      receptors on nerve terminals of GABAergic, glutamatergic and aspartatergic
      neurons in the rostral ventral medulla. These findings also suggest the existence
      of another inhibitory transmitter that may mediate the actions of clonidine to
      decrease sympathetic outflow from the RVL.

PMID- 1982241
TI  - Motor neurone disease serum and beta-N-methylamino-L-alanine stimulate
      thyrotrophin-releasing hormone production by cultured brain cells.
AB  - We have investigated the effects of serum from patients with motor neurone
      disease (MND) and of the plant-derived excitotoxin beta-N-methylamino-L-alanine
      (L-BMAA) on thyrotrophin-releasing hormone (TRH) and somatostatin (SS) production
      by fetal rat brainstem cell cultures. Compared to age- and sex-matched normal and
      neurological disease control sera, MND sera produce a 2- to 3-fold increase in
      TRH content of the cultures with no change in SS levels. L-BMAA produced similar
      dose-related and stereospecific effects on the cultures increasing TRH levels to
      2-fold with no effect on SS levels. These findings may be relevant to the
      understanding of the aetiology of MND.

PMID- 1982242
TI  - Amyloid beta/A4 protein precursor is bound to neurofibrillary tangles in
      Alzheimer-type dementia.
AB  - Localization of amyloid beta/A4 protein precursor (APP) in Alzheimer's
      neurofibrillary tangles (NFT) was examined immunohistochemically. Antiserum
      directed to N-terminal of APP intensely labeled intracellular NFT and some
      neuropil threads. The NFT, extracted from Alzheimer brains by detergent
      treatments, were also immunoreactive with this antiserum. Antisera to other parts
      of APP labeled NFT after the formic acid pretreatment. However, Western blot
      analysis of NFT demonstrated no immunoreactive bands with APP antiserum. These
      findings suggest that APP is a minor component of the NFT.

PMID- 1982243
TI  - Cografts of adrenal medulla with peripheral nerve enhance the survivability of
      transplanted adrenal chromaffin cells and recovery of the host nigrostriatal
      dopaminergic system in MPTP-treated young adult mice.
AB  - Schwann cells from transected peripheral nerve segments are known to produce
      nerve growth factor (NGF). We performed adrenal medullary grafts or cografts of
      adrenal medulla and sciatic nerve into the striatum of MPTP-treated young adult
      mice, and compared the survivability of grafted chromaffin cells and the recovery
      of intrinsic host DA fibers using computerized image analysis of tyrosine
      hydroxylase (TH)-immunoreactive (IR) fibers and neurochemical analysis with high
      performance liquid chromatography (HPLC). Adrenal medullary chromaffin cells
      cografted with sciatic nerve survived better than those in adrenal grafts alone;
      host DA fiber recovery was more prominent in mice with cografts than in mice with
      adrenal grafts alone. A large number of TH-IR surviving cells in cografted mice
      showed long neuronal processes which were rarely seen in the mice receiving
      adrenal graft alone. We conclude that cograft of adrenal medulla and sciatic
      nerve promotes intrinsic host DA fiber recovery better than adrenal medulla
      grafts alone, and that survivability of grafted chromaffin cell may promote host
      DA fiber recovery. Adrenal medullary autografts have been used in patients with
      Parkinson's disease; we suggest that if this approach is to be used in the
      future, methods to increase the survivability of grafted chromaffin cells, such
      as co-grafting with pieces of peripheral nerve, be considered to enhance the
      survivability of the chromaffin cells, which might be closely related to the
      functional recovery of the patients by this grafting procedure. Of course, such
      strategies as the present cografting approach must be demonstrated to work in
      older animals using older donor tissue before proceeding to this next step in
      humans.

PMID- 1982244
TI  - Effect of subchronic administration of ethanol and methylmercury in combination
      on the tissue distribution of mercury in rats.
AB  - The effect of oral administration for 14 weeks of 8 g.kg-1.day-1 ethanol and 0.5
      mg.kg-1.day-1 methylmercuric chloride in combination to rats fed isocaloric diets
      has been investigated. Ethanol, in contrast to published studies, failed to
      influence the tissue distribution of methylmercury and its inorganic mercury
      metabolite in brain and kidney, and did not inhibit the increase in kidney weight
      induced by methylmercury. Ethanol and methylmercury, in combination and
      individually, reduced the renal but not the hepatic activity of gamma
      glutamyltransferase, but did not affect the renal and biliary concentration of
      reduced glutathione. Further study is required to determine the circumstances
      under which ethanol can influence the tissue distribution of methylmercury and
      its inorganic mercury metabolite.

PMID- 1982245
TI  - Invasive electrophysiologic studies as predictor of sudden death and for
      treatment of patients with aborted sudden death.

PMID- 1982246
TI  - Electrophysiological effects of a chemical defibrillatory agent, dibenzepin.
AB  - STUDY OBJECTIVE: The aim was to study the cellular cardiac electrophysiological
      effects of the antifibrillatory drug, dibenzepin. DESIGN: Standard microelectrode
      techniques were used to measure the effects of dibenzepin (3 microM, 9 microM) on
      conduction time, Vmax and input resistance in canine papillary muscles, in vitro,
      at three paced cycle lengths (1000, 400, 200 ms). Results were compared when
      adrenaline (0.5-5 microM) or propranolol (0.2 microM) were present. EXPERIMENTAL
      MATERIAL: Papillary muscles (n = 25) from hearts of adult mongrel dogs, weight 13
      18 kg, were used. MEASUREMENTS AND MAIN RESULTS: Dibenzepin, at 3 microM, caused
      significant reduction of Vmax at cycle lengths less than or equal to 400 ms.
      Paradoxically, the conduction time decreased at all three cycle lengths when
      measured along the longitudinal axis of the fibre between two microelectrodes
      spaced 2 mm apart. Superfusion of dibenzepin (3 microM) and propranolol (0.2
      microM) significantly reduced Vmax and lengthened conduction time at all cycle
      lengths. Dibenzepin reduced input resistance from 1.45 to 0.76 M omega, thereby
      suggesting that improved coupling may occur between cells to account for the
      shortening of conduction time. Propranolol blocked these results. CONCLUSION: The
      defibrillatory action of dibenzepin may be related to a decreased intercellular
      resistance caused by increased catecholamine availability during fibrillation.
      This would result in improved conduction and, thereby, a decrease of the critical
      number of asynchronous re-entrant circuits necessary to maintain fibrillation.

PMID- 1982247
TI  - Tissue-specific expression of mRNA in mouse lymphocytes detected by v-fos but not
      by human c-fos DNA probes.
AB  - Transcription of the c-fos gene is known to be induced transiently by many types
      of cellular stimuli in various cultured cell lines; however, several authors have
      reported that the c-fos gene is constitutively transcribed in lymphoid cells. We
      detected, in fact, abundant transcripts which hybridized with a v-fos DNA probe
      in nuclear run-off transcripts and poly(A)+ RNA of both quiescent mouse splenic
      lymphocytes and unstimulated monocytic tumor cell lines. However, human c-fos
      cDNA did not hybridize with most of these transcripts. No signal was detected by
      v-fos probe in nuclear run-off transcripts of 3T3 fibroblasts, and c-fos was
      inducible in both the 3T3 cells and the monocytic tumor cell lines. In quiescent
      lymphocytes, only the 0.3 kb HincII-PvuII portion of v-fos DNA, which contains a
      repeat of CAAAA, hybridized with these transcripts; neither other parts of v-fos
      nor human c-fos DNAs did. These results suggest that a significant portion of the
      previously reported 'constitutive' transcripts detected by v-fos DNA in
      lymphocytes and monocytes are not transcripts of c-fos but of other sequences
      which are specifically expressed in lymphoid cells and have homology with the 0.3
      kb HincII-PvuII fragment of v-fos.

PMID- 1982248
TI  - [Determination of lymphocyte subsets in pulmonary tuberculosis by Mc-Ab- rosette
      reagent method].
AB  - The lymphocyte subsets in peripheral blood were determined in 73 cases of active
      pulmonary tuberculosis and 40 healthy subjects using rosette reagent of
      monoclonal antibody (McAb) to anti-T lymphocyte. The results showed that the
      percentages of T3, T4, T8, and T4/T8 ratio were 54.3 +/- 6.7%, 34.3 +/- 7.9%,
      35.5 +/- 10.0%, 1.0 +/- 0.4 of patients group 66.3 +/- 7.9%, 45.3 +/- 6.3%, 29.9
      +/- 5.8% and 1.6 +/- 0.3 of healthy control group respectively. There was
      statistically significant difference between these two groups (P less than 0.01).

PMID- 1982249
TI  - [Reappearance of dengue in New Caledonia from 1985 to 1988].
AB  - From 1971 to 1980, dengue outbreaks occurred in New-Caledonia due to dengue
      viruses type 2, 1 and 4 successively. After an eclipse of four years, dengue
      reappeared in 1985 through 1988. Out of 109 cases confirmed by virus isolation,
      dengue serotypes 1, 2, 3 and 4 caused 15, 23, 17 and 54 cases respectively; in 28
      other cases, the Flavivirus type could not be identified and in 26 cases an
      Alphavirus (Ross River) was pointed out. The DEN 3 virus, unknown in New
      Caledonia before 1985, was discretely transmitted until 1988. The 1989 outbreak
      showed the necessity of rigorous vector control measures.

PMID- 1982250
TI  - [Survey of mosquitoes in the department of Aisne (France): Parc de l'Ailette in
      1989].
AB  - Before undertaking a campaign of mosquito control in a tourist area, a survey on
      the breeding sites and the present species has been done between March and
      November 1989. Fifteen species have been found, ten of them new for the
      department.

PMID- 1982251
TI  - Non-HLA genetic factors and insulin dependent diabetes mellitus in the Japanese:
      TCRA, TCRB and TCRG, INS, THY1, CD3D and ETS1.
AB  - Polymorphism of the genes encoding the alpha, beta, and gamma chains of the human
      T-cell receptor (TCRA, TCRB, and TCRG), insulin gene (INS), and three closely
      linked polymorphic genes on chromosome 11q23, Thy-1 (THY1), T3-D (CD3D), and c
      ets proto oncogene (ETS1) were investigated among 56 unrelated patients with
      insulin-dependent diabetes mellitus (IDDM) and 48 healthy controls. Only eight of
      the 17 enzymes examined revealed restriction fragment length polymorphism (RFLP),
      with the use of TCRA, TCRB, and TCRG. No significant association was observed.
      Polymorphism after BglI, SstI, and TaqI digestion was observed for the INS gene.
      In consideration of the three classes within the insulin-gene-linked DNA
      polymorphism alleles, A1 and more rarely A2 alleles were found, but with no
      significant frequencies. THY1 and CD3D genes were polymorphic after MspI
      digestion but no significant association was observed. Conversely, the ETS1 gene
      showed polymorphism after TaqI, SstI, and AvaII were used. Only a significant
      AvaII-polymorphic fragment (p less than 0.03) was found. However, this
      significant association disappeared when the correct p value was applied. These
      results were compared to findings in Caucasians and some differences were noted.
      The polymorphism observed in this study may be useful in genetic studies on
      immunologically affected populations.

PMID- 1982252
TI  - Antibodies to CD4 in individuals infected with human immunodeficiency virus type
      1.

PMID- 1982253
TI  - New method for isolation of venom from the sea anemone Actinia cari. Purification
      and characterization of cytolytic toxins.
AB  - 1. Venom from the sea anemone Actinia cari was obtained by the "milking" method.
      Two lethal and hemolytic polypeptide toxins, caritoxins I (CTX I) and II (CTX
      II), were isolated with gel and ion exchange chromatography. 2. The mol. wt of
      the pure toxin was 19,800. The isoelectric points of CTX I and II were 9.45 and
      10.0, respectively. The toxins had similar amino acid compositions lacking
      cysteine. 3. The intravenous CTX I and CTX II lethal dose (LD50) in mice was
      found to be 54 +/- 25 and 90 +/- 1 micrograms/kg, respectively. Their hemolytic
      activity was inhibited by sphingomyelin.

PMID- 1982254
TI  - [Relationship between serum antibody to Bacteroides gingivalis and clinical
      parameters in periodontitis patients].
AB  - Prevalence and proportion of black-pigmented Bacteroides species (BPB) in
      supragingival and subgingival plaque were determined in ten adult periodontitis
      patients. Serum antibody against Bacteroides gingivalis (Bg) of these patients
      were tested using ELISA. Clinical parameters (PI, GI, PD, AL) were collected
      prior to blood withdrawn. Results showed that BPB were detected in all patients.
      Mean serum anti-Bg IgG level was significantly greater in the patient group than
      that in healthy control group. Although the sample size was too small to show
      statistical difference, there was a trend showing the sera anti-Bg IgG level
      tended to be greater in accordance with the increase of disease severity and
      BPB%.

PMID- 1982255
TI  - [The relationship between IL-2 production and T cell subpopulation in patients
      with systemic lupus erythematosus].
AB  - The authors reported IL-2 production and T cell subpopulation of peripheral blood
      lymphocytes from patients with systemic lupus erythematosus(SLE). The results
      indicated that patients with SLE showed a decreased IL-2 production and a
      decreased T4/T8 cell ratio. The relation between IL-2 production and T4/T8 ratio
      was also observed. Our data suggest that IL-2 production correlates significantly
      with T4/T8 cell ratio.

PMID- 1982256
TI  - [Diagnosis and treatment of pheochromocytoma. Report of 49 cases].
AB  - From 1958 to 1990, 49 patients with pheochromocytoma were treated surgically. The
      tumors were located in the adrenal gland in 34 cases (69.4%) and in the extra
      adrenal gland in 15 cases (30.6%). In two cases the tumors were
      pheochromoblastoma and in 6 cases the tumors were asymptomatic. Determination of
      urine VMA has a screening value for patients with pheochromocytoma. The
      corresponding rate was 91.3% by B-ultrasonography to localize the tumor. CT
      scanning can clearly identify pheochromocytoma of its size and relation to the
      adjacent organs, which may provide a basis for the selection of operative
      methods. Administration of alpha-adrenoceptor blocking drugs and expanding blood
      volume are very important procedures, which can effectively reduce the mortality
      rate.

PMID- 1982257
TI  - [Symposium on postoperative infections of open heart surgery].

PMID- 1982258
TI  - [The role and mechanism of berberine on coronary arteries].
AB  - Berberine increased coronary artery flow of anesthetized open-chest canines and
      isolated guinea pig hearts with ventricular fibrillation induced by electric
      stimulus. The rabbits were protected by berberine from ischemic ECG changes
      caused by posterior pituitary hormones. Spasm of isolated swine coronary arterial
      rings responded to ergometrine was able to be prevented and treated effectively
      by berberine. On isolated swine coronary arterial strips, berberine shifted
      norepinephrine cumulative dose-response curve rightward parallelly without
      decreasing the maximal response. The pA2 value was 6.7. Contraction treatment
      effects post-PBMV, the cardiac function tended to decline with time, the decrease
      of ejection fraction, stroke volume and cardiac output were 0.03 +/- 0.007, 5.44
      +/- 1.04 ml and 0.44 +/- 0.08 L/min respectively. This might be due to the
      unsuccessful control of activity of rheumatism after PBMV and it is necessary to
      pay attention to in the future.

PMID- 1982259
TI  - [Effects of terazocin on hypertensive patients].

PMID- 1982260
TI  - A case of first trimester prenatal diagnosis of 21-hydroxylase deficiency with
      human complement C4 cDNA probe.
AB  - Early prenatal diagnosis of 21-hydroxylase (21-OHase) deficiency would enable
      treatment to be done to protect the fetus from masculinization and/or life
      threatening adrenal crisis at birth. We report here the prenatal diagnosis of 21
      OHase deficiency with human complement component C4 cDNA to probe DNA from
      chorionic villi at 10 weeks of gestation. Southern analysis with human C4 cDNA
      identified TaqI restriction fragment length polymorphisms (RFLPs) in the family.
      Family analysis with these RELPs showed that the fetus was not affected at
      greater than 99% probability, because the frequency of recombination between the
      21-OHase B gene and the C4 gene would be extremely low.

PMID- 1982261
TI  - Serum hyaluronan concentration determined by radiometric assay in patients with
      pretibial myxedema and Graves' ophthalmopathy.
AB  - The serum concentration of hyaluronan (HA) was measured by radiometric assay in
      patients with pretibial myxedema (PTM) and Graves' ophthalmopathy (GO). The mean
      HA concentration in the patients (n = 8) was 21.2 +/- 15.3 (mean +/- SD)
      microgram/l, while that of Graves' disease without skin or eye involvement (n =
      7) was 23.5 +/- 11.0 (mean +/- SD) microgram/l and that of the control (n = 8)
      was 25.5 +/- 16.4 (mean +/- SD) microgram/l. We conclude that local accumulation
      of glycosaminoglycan in PTM or GO is not associated with an increase in the serum
      HA concentration.

PMID- 1982262
TI  - European Group for Breast Cancer Screening. Recommendations for breast cancer
      screening.

PMID- 1982263
TI  - Dissociation constants and relative efficacies estimated from the functional
      antagonism of beta-adrenoceptor agonists on transmural stimulation in rat vas
      deferens.
AB  - In rat vas deferens, the beta-adrenoceptor agonists, isoprenaline, salbutamol,
      terbutaline and fenoterol, inhibited the contractions elicited by transmural
      electrical stimuli to an extent which depended on voltage magnitude. The dose
      response curves for these agonists were shifted slightly to the right when the
      amplitude of the twitch was increased up to twice its original size.
      Consequently, the values of pD2 for the respective agonists obtained with a '50%
      twitch' and a '100% twitch' were: 7.6 and 7.5, 6.8 and 6.6, 6.2 and 6.0, 7.6 and
      7.4. In addition, the maximal effects of the agonists were significantly reduced
      (by 13-18%). The values of other parameters for the same agonists, calculated
      according to a model for functional antagonism, were: negative log of
      dissociation constants (pKa): 7.2, 6.3, 6.2 and 7.2; percent receptors occupied
      to induce a half-maximal effect (y50): 42, 46, 63, and 53; relative intrinsic
      efficacy (er): 1.0, 0.9, 0.7, and 0.8. The usefulness of this type of functional
      antagonism as an alternative method for the estimation of drug-receptor
      parameters is discussed in the light of receptor theory.

PMID- 1982264
TI  - Chloral hydrate anesthesia antagonizes the neurotoxicity of 3,4
      methylenedioxymethamphetamine.
AB  - We report that maintaining rats under chloral hydrate anesthesia for the first 3
      h following the administration of 3,4-methylenedioxymethamphetamine (MDMA) blocks
      the decrease in forebrain concentrations of 5-hydroxytryptamine (5-HT) measured 1
      week later. In contrast, the acute effect of MDMA (3 h) on forebrain 5-HT was not
      altered by the anesthetic. This protective effect of chloral hydrate was not due
      to an anesthetic-induced hypothermia but may be related to the hypothesized role
      of dopamine in the neurotoxic effects of MDMA.

PMID- 1982265
TI  - Effects of methylenedioxymethamphetamine on the release of monoamines from rat
      brain slices.
AB  - The effects of 3,4-methylenedioxymethamphetamine (MDMA) on monoamine release were
      investigated in superfused slices of rat striatum and hippocampus. MDMA (10
      microM) increased the resting release of radioactivity from slices incubated in
      [3H]dopamine, [3H]5-hydroxytryptamine or [3H]noradrenaline. These effects of MDMA
      (10 microM) were blocked by the neuronal uptake inhibitors, cocaine (10 microM),
      fluoxetine (1 microM) and desmethylimipramine (1 microM), respectively. MDMA (10
      microM) enhanced the stimulation-induced efflux of radioactivity from slices
      incubated in [3H]noradrenaline but not from slices incubated in [3H]5
      hydroxytryptamine or [3H]dopamine. These results demonstrate for the first time a
      direct noradrenaline-releasing action of MDMA and differential effects of MDMA on
      the stimulation-induced release of noradrenaline, dopamine and 5
      hydroxytryptamine from rat superfused brain slices.

PMID- 1982266
TI  - A novel in vivo test for drugs affecting central serotonergic and adrenergic
      systems.
AB  - In urethane-anaesthetized rats, myoclonic twitches of the anterior digastricus
      muscle were evoked by L-5-hydroxy-tryptophan (L-5-HTP, 50-100 mg/kg iv.), the
      serotonin (5-HT) receptor agonist, quipazine (1-8 mg/kg i.v.) and the 5-HT
      releaser, fenfluramine (4-8 mg/kg i.v.). The effect of L-5-HTP or quipazine on
      the frequency of twitches was inhibited by the 5-HT receptor antagonist
      cyproheptadine. Also L-DOPA (100 mg/kg i.p.) or the alpha 1-adrenoceptor agonist,
      cirazoline (0.3-3 mg/kg i.v.) evoked twitches of the muscle which were inhibited
      by the alpha 1-adrenoceptor antagonist, prazosin. In decerebrate, artificially
      respired rats, neither L-5-HTP nor L-DOPA evoked the twitches. The frequency of
      twitches evoked by fenfluramine but not by L-DOPA was increased by the alpha 2
      adrenoceptor agonist, clonidine (0.2 and 0.4 mg/kg i.v.); clonidine's effect was
      abolished by the alpha 2-adrenoceptor antagonist, yohimbine. The beta 2
      adrenoceptor agonist, salbutamol (0.01-1 mg/kg i.v.) had no effect on
      fenfluramine-induced twitches. It is concluded that (1) activation of 5-HT
      receptors or alpha 1-adrenoceptors in the brain of urethane-anaesthetized rats
      evokes twitches of the anterior digastricus muscle, and (2) this preparation can
      be utilized as a test to study the action of compounds on central 5-HT and
      adrenergic systems.

PMID- 1982267
TI  - Stimulation of both D1 and D2 dopamine receptors increases behavioral activation
      and ascorbate release in the neostriatum of freely moving rats.
AB  - Electrochemically modified carbon-fiber electrodes were used to assess the
      effects of indirect (amphetamine and GBR-12909) as well as direct D1 (SKF-38393)
      and D2 (quinpirole) dopamine agonists on extracellular ascorbate in the
      neostriatum of awake, behaving rats. Relative to controls, 2.5 mg/kg d
      amphetamine and 20.0 mg/kg GBR-12909 produced marked behavioral activation
      concomitant with a significant increase in ascorbate. Comparable effects were
      observed following the combined administration of 10.0 mg/kg SKF-38393 and 1.0
      mg/kg quinpirole, but not after either of these drugs alone. Thus, behavioral
      activation and release of neostriatal ascorbate were closely related to the
      concurrent stimulation of both D1 and D2 dopamine receptors.

PMID- 1982268
TI  - Predominant acetylcholine-induced vasoconstriction in isolated, perfused simian
      facial veins.
AB  - Using the cannula insertion method, we investigated the vascular response to
      acetylcholine (ACh) and other vasoactive substances. ACh consistently induced
      only vasoconstriction, whereas isoproterenol and norepinephrine usually induced
      dilatation. Vasoconstriction induced by phenylephrine was less potent than that
      induced by ACh. Clonidine and xylazine did not induce significant vascular
      responses. ACh-induced constrictions were readily inhibited by atropine and
      slightly potentiated by physostigmine. They were slightly but significantly
      inhibited by pirenzepine (a muscarinic M1-receptor antagonist), but not
      influenced by AF-DX 116 (a M2-receptor antagonist). 4-DAMP (4-diphenylacetoxy N
      methylpiperidine; a M3-receptor antagonist), strongly inhibited the ACh-induced
      constrictions. They were not modified by bunazosin but slightly suppressed by
      diltiazem. Removal of the endothelium did not significantly modify the ACh
      induced constrictions. From our results, we conclude that the simian facial vein
      has many constrictory muscarinic receptors, especially of the M3 subtype.

PMID- 1982269
TI  - Anticonvulsant action of SCH 23390 in the striatum of the rat.
AB  - This study investigates the role of forebrain D1 receptors in the motor
      expression of seizures induced by pilocarpine. Conscious rats receiving bilateral
      intracaudate injections of saline, just failed to convulse to 200 mg/kg
      pilocarpine, but responded vigorously to 600 mg/kg of the cholinomimetic. LY
      171555 significantly protected rats against 600 mg/kg pilocarpine, when delivered
      into the anterior striatum, as also did SCH 23390, from all rostrocaudal levels
      of the striatum. Intrastriatal SKF 38393 or CY 208-243 neither facilitated nor
      ameliorated pilocarpine-induced convulsions. SCH 23390 was also anticonvulsant
      from the nucleus accumbens, while intra-accumbens CY 208-243 was without effect.
      It is concluded that SCH 23390 affords protection against pilocarpine-induced
      limbic motor seizures by blocking the effects of endogenous dopamine released
      tonically onto D1 receptors in the corpus striatum and nucleus accumbens. The
      inability of additional D1 receptor stimulation to intensify such seizures, could
      indicate that forebrain D1 receptors are already maximally stimulated by the
      endogenous transmitter.

PMID- 1982270
TI  - Bunazosin induces use-dependent slowing of conduction in guinea-pig ventricular
      myocardium.
AB  - The use-dependent effects of bunazosin on the maximal rate of rise (Vmax) of the
      action potential and conduction velocity were studied in isolated papillary
      muscles of guinea-pig. Standard microelectrode techniques were used to monitor
      the conduction and action potential of the muscles. In the presence of 30 microM
      bunazosin, the time constants for the start of the use-dependent inhibition of
      Vmax during a 0.2, 1, 2 and 3 Hz stimulation were (means +/- S.E.M. in s) 30.9 +/
      8.0, 15.0 +/- 1.6, 7.4 +/- 0.9 and 3.9 +/- 0.7 (n = 4) and those for conduction
      velocity were 17.3 +/- 2.3, 17.3 +/- 5.2, 6.5 +/- 0.9 and 3.4 +/- 0.2,
      respectively. These results showed that in the cardiac ventricular muscle of the
      guinea-pigs, bunazosin produces use-dependent changes in conduction velocity with
      onset kinetics comparable to those measured simultaneously using Vmax. The
      characteristics of the use-dependent inhibition of conduction velocity induced by
      bunazosin are similar to those found with slow kinetic drugs such as disopyramide
      rather than with fast ones.

PMID- 1982271
TI  - Isolated bovine cerebral arteries from rostral and caudal regions: distinct
      responses to adrenoceptor agonists.
AB  - Responsiveness to norepinephrine and related agents was compared in isolated
      bovine anterior cerebral (ACA). middle cerebral (MCA), intracranial internal
      carotid (ICA), posterior communicating (PCOM), posterior cerebral (PCA) and
      basilar arteries (BA). Norepinephrine contracted the strips from ACA, MCA and
      ICA, but relaxed those from PCOM, PCA and BA. In the presence of propranolol, the
      amine-induced contractions tended to be potentiated in ACA, MCA and ICA, and the
      relaxations in PCOM, PCA and BA were reversed to contractions. The maximum
      contractions induced by norepinephrine in ICA and ACA treated with propranolol
      were significantly greater than those in PCA and BA, but the EC50 values did not
      differ among arteries. In ACA and MCA, the contractions induced by phenylephrine
      were greater than those induced by clonidine. The contractions induced by
      norepinephrine and phenylephrine were attenuated by prazosin but not influenced
      by yohimbine in ACA and MCA treated with propranolol. These findings indicate
      that the responses to norepinephrine evidently differ in bovine cerebral arteries
      of rostral (ACA, MCA and ICA) and caudal regions (PCOM, PCA and BA), possibly due
      to different functioning of alpha/beta receptors. The amine-induced contraction
      predominantly seen in the rostral arteries appears to be associated with
      activation of the alpha 1 adrenoceptor subtype.

PMID- 1982272
TI  - Repeated stimulation of dopamine D1 receptors enhances the effects of dopamine
      receptor agonists.

PMID- 1982273
TI  - European Orthodontic Society. 66th Congress. Copenhagen, 1990 26-30 June.
      Abstracts.

PMID- 1982274
TI  - Effects of chronic treatment with the leukotriene D4-antagonist compound LY171883
      on B6C3F1 mice.
AB  - A 2-year toxicity/oncogenicity study was done to evaluate the potential effects
      of the leukotriene antagonist LY171883 in B6C3F1 mice. Dietary concentrations of
      LY171883 during the initial 7 months of the study were 0.0, 0.005, 0.015, or
      0.05% but were increased to 0.0, 0.0075, 0.0225, or 0.075% during Months 7
      through 24. The estimated average daily compound intake was 0.0, 7.3, 22.5, or
      80.5 mg/kg for males and 0.0, 9.2, 27.5, or 95.9 mg/kg for females. Survival was
      not adversely affected by treatment, however, body weight of males and females in
      the high dose group was significantly lower than that of controls. The chronic
      toxicity was localized primarily to the liver. Liver weights were increased in
      males in the high dose group and in females in the mid and high dose groups.
      Microsomal p-nitroanisole-O-demethylase activity was increased in mid and high
      dose females. Hepatic peroxisomal beta-oxidation was increased approximately
      twofold in both sexes in the high dose group only. Centrilobular eosinophilic
      granular change of hepatocytes was a common histopathologic finding in male and
      female mice in the high dose group, with the incidence and severity being greater
      in females. An increased incidence of hepatocellular carcinomas was observed in
      female mice in the mid and high dose groups. The number of male mice in the high
      dose group with hepatocellular carcinomas was higher than that of controls but
      the change was not statistically significant. Hepatocellular adenomas were
      increased in females in the high dose group but not in males. All groups of
      treated females had increased nodular hepatocellular hyperplasia.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1982275
TI  - A partial map of the barley genome incorporating restriction fragment length
      polymorphism, polymerase chain reaction, isozyme, and morphological marker loci.
AB  - Nine low copy number genomic DNA clones, a ribosomal sequence, and seven cDNA
      clones were found to identify polymorphisms in cultivated barley (Hordeum vulgare
      L.). An F2 population consisting of 100 plants was produced from a cross between
      a high-yielding two-rowed feed barley cultivar and a genetic marker stock
      homozygous for nine recessive and one dominant morphological marker genes.
      Through the use of these 10 well-distributed marker genes, five previously mapped
      isozyme loci, and two storage-protein loci, the approximate recombinational
      location for each of 17 restriction fragment length polymorphism loci was
      estimated. One clone, pMSU21, identified variation that appeared to be the result
      of a small insertion-deletion event that differentiated two-rowed and six-rowed
      genotypes. This difference was characterized, and one allele was sequenced.
      Oligonucleotide primers that flanked the insertion-deletion event were
      synthesized, and DNA samples from the F2 population were subjected to polymerase
      chain reaction sequence amplification. The variation identified by this technique
      was determined to be allelic to the variation identified using pMSU21 in Southern
      blot analysis. Maps of previously undescribed informative clones are included.

PMID- 1982276
TI  - [Adjustment of intermodal relations between subjective evaluation of
      psychological state and psychophysiological functions in performing precision
      operations].
AB  - 156 operators were examined with regard to the psychophysiological state indices
      complex. Evaluation was made of the correlation between the investigated
      parameters and the operators' personal perceptions of their state. It was
      revealed that the changes on the scales of "personal perception" in case with the
      local fatigue were characteristic of specific working operations, whereas the
      "activity" scale indices correlated with the systemic fatigue dynamics.

PMID- 1982277
TI  - Effect of HIV-1 infection on CD4 cells in a hemophilia cohort.

PMID- 1982278
TI  - Prenatal diagnosis of inherited hemoglobinopathies.

PMID- 1982279
TI  - Molecular analysis of severe von Willebrand disease in Italian patients.

PMID- 1982280
TI  - Antihistaminic activity and side effect profile of epinastine and terfenadine in
      healthy volunteers.
AB  - New H1-receptor antagonists are assessed not only for their H1 antihistaminic
      activity but also for their central nervous system (CNS) side effects. Fifteen
      healthy subjects received a once daily dose of 5 mg, 10 mg or 20 mg of
      epinastine, or a twice daily dose of 60 mg of terfenadine or placebo in a
      randomized double-blind (double-dummy) crossover study. The response to histamine
      induced skin wheals was compared. CNS effects were evaluated by a multiple
      reaction time task, a finger tapping test and a self-rating scale (Bf-S von
      Zerssen) to assess mood state. Epinastine attenuated the wheal size in response
      to histamine in a dose-dependent manner. In addition, all epinastine dosages had
      a distinctly faster onset of action than terfenadine. All active treatments (5
      mg, 10 mg, 20 mg epinastine and 60 mg terfenadine) attained their maximum effects
      4 h after administration. At this time point and also 12 h after administration,
      20 mg of epinastine were significantly more effective than 60 mg of terfenadine.
      Single 10 mg and 20 mg doses of epinastine were as effective as terfenadine given
      twice daily, and significantly more effective than placebo 24 h after drug
      administration (i.e. 12 h after the second dose of terfenadine). The psychometric
      tests for CNS effects did not reveal any difference among epinastine, terfenadine
      and placebo. In conclusion, epinastine is one of the most effective peripherally
      acting H1 antagonist which lacks significant CNS side effects and is suitable as
      a once daily dosage regimen.

PMID- 1982281
TI  - Effect of cimetidine on the pharmacodynamics, pharmacokinetics and
      biotransformation of a single oral dose of alpidem.
AB  - Alpidem is a new imidazopyridine derivative acting as an anxiolytic which may be
      prescribed with H2 receptor antagonists in patients with peptic ulcer. An open
      trial design (cimetidine, 1 g daily for 22 days) was carried out in eight healthy
      subjects. Alpidem, 50 mg was administered orally at 09:00 prior to any treatment
      and on days 2 and 18 of the cimetidine treatment period. Antipyrine clearance was
      also determined before and on day 21. Under these experimental conditions, the
      inhibitory effect of cimetidine on the cyt. P-450 monooxygenase system has been
      demonstrated (reduced clearance of antipyrine and its three main urinary
      metabolites) but the plasma pharmacokinetics of alpidem and its three main plasma
      metabolites did not appear to be modified. Alpidem induced no sedative effect but
      there was an insignificant trend to impair slightly the psychometric tests 1 h
      post-drug by the combination with cimetidine. Pharmacokinetic and pharmacodynamic
      evaluations did not show significant interactions with cimetidine following
      alpidem 50 mg administration.

PMID- 1982283
TI  - The joule, the adipocyte and obesity. A symposium held at the 5th annual NAASO
      Conference. Banff, 1988. Proceedings.

PMID- 1982282
TI  - T3 plus high doses of beta-blockers: effects on energy intake, body composition,
      bat and heart in rats.
AB  - The effects of a combined treatment with supraphysiological doses of the thyroid
      hormone T3 (15 micrograms/kg BW/day, s.c.) and high doses of a predominant beta 1
      blocker (atenolol, 12.5 and 25 mg/kg BW, 3X/day, s.c.) or a non-specific beta
      blocker (propranolol, 5 mg/kg BW s.c. and 33 mg/kg BW p.o., each 3X/day) on
      energy intake, body composition and the heart were studied in overfed rats with
      an increased body fat content. The goal of the study was to investigate whether
      the above treatment constitutes a therapy for obesity in that T3 causes weight
      and fat loss and the beta-blockers prevent the unwanted T3-effects on the heart
      (tachycardia and increased heart weight). T3 did not increase energy intake above
      the level seen in overfed animals. It caused loss of body weight due to loss of
      fat but not protein, an increase in interscapular brown adipose tissue (IBAT)
      weight and fat, tachycardia and an increase in heart weight. Atenolol and
      propranolol blocked T3-induced tachycardia. With the exception of the highest
      propranolol dose which abolished the T3-induced increase in IBAT fat content, the
      beta-blockers did not modify the other T3 effects. Thus, in spite of the weight
      and fat loss and the lack of significant protein loss and tachycardia observed
      under T3/high dose beta-blockers treatment, the T3-induced increase in heart
      weight makes this treatment unsuitable as a therapy for obesity.

PMID- 1982284
TI  - Effects of age, neuropsychological impairment, and medication on regional
      cerebral blood flow in schizophrenia and major affective disorder.
AB  - Reports of abnormalities of regional cerebral blood flow (rCBF) in patients with
      schizophrenia and major affective disorder are contradictory. To gain a better
      understanding of the possible sources of these contradictions, the rCBF and
      neuropsychological functioning of 15 schizophrenics, 15 patients with major
      affective disorder, and 15 age-matched controls were studied. No group
      differences in overall rCBF, percent frontal deviation in flow, or rCBF
      asymmetries were observed. Both overall rCBF and percent frontal deviation of
      rCBF were reduced with greater age and with increasing neuropsychological
      impairment. Dosage of neuroleptic medication was associated with reduced whole
      brain flow, not with percent frontal deviation flow. Previously reported
      differences in the resting rCBF of schizophrenics might be more closely related
      to the age of the subjects and to their neuropsychological impairment rather than
      the inherent progression of the disorder.

PMID- 1982285
TI  - Experimental cryptorchidism in the adult mouse: I. Qualitative and quantitative
      light microscopic morphology.
AB  - Morphologic changes in the testes of adult mice after experimentally induced
      cryptorchidism were studied by light microscopy and stereology. Increasing
      duration of cryptorchidism resulted in a gradual decrease in the volume of
      seminiferous tubules per testis, and this was associated with germ cell
      degeneration. The volumes of Sertoli cell lipid droplets increased, and dilations
      of the intercellular space between the Sertoli cell junctions was observed in the
      cryptorchid testis. The luminal volume of the seminiferous tubule was reduced by
      50% after 28 days of cryptorchidism. However, the volumes of intertubular tissue
      and Leydig cells in control and cryptorchid testes were not significantly
      different. Leydig cell number per testis increased, and the average volume of a
      Leydig cell decreased gradually with the progression of the cryptorchid state.
      The volume of the connective tissue cells in the intertubular area increased, but
      no significant volume change was observed in the volume of intertubular
      macrophages. After 28 days, the cryptorchid testis contained a significantly
      increased volume of blood vessels and a reduced volume of lymphatic space per
      testis. These observations clearly demonstrate that, although the mouse is a
      species closely related to the rat, the morphologic changes that occur in the
      Leydig cell population after induction of experimental cryptorchidism in this
      species is different.

PMID- 1982287
TI  - 7th Danube Symposium on Chromatography. Leipzig, August 21-25, 1989.

PMID- 1982288
TI  - Chiral stationary phase for the facile resolution of beta-adrenoceptor blocking
      agents.

PMID- 1982286
TI  - Experimental cryptorchidism in the adult mouse: II. A hormonal study.
AB  - Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and
      testosterone levels and secretory capacity of the in vitro stimulated testis were
      determined in control and bilateral cryptorchid mice after 7, 14, 21, and 28
      days. In a separate study, serum FSH, LH, and testosterone levels were measured
      in unilateral and bilateral cryptorchid, hemicastrate, and bilaterally castrate
      adult mice after 28 days of treatment. Serum FSH levels were significantly
      increased in bilaterally cryptorchid mice compared to controls (0 days) at 7, 14,
      21, and 28 days, but serum LH and testosterone levels did not change. At 28 days,
      the elevated serum FSH levels in the unilateral and bilateral cryptorchid mice
      were not different than those in hemicastrate mice. However, the FSH levels in
      bilaterally castrate mice after 28 days were significantly higher than all other
      groups. Serum LH and testosterone levels were significantly different only in the
      bilaterally castrate group, compared to control levels. Both the normal and
      cryptorchid testes of all ages studied were capable of producing equal levels of
      testosterone in vitro, both basally and with a human chorionic gonadotropin (hCG)
      dose of 700 mIU/ml (maximum stimulatory dose for both the normal and the 28 day
      cryptorchid testes). Changes that occur in mice with experimentally induced
      cryptorchidism are not identical to those seen in the rat. Serum FSH levels
      increase, but no changes occur in serum LH and testosterone levels. Additionally,
      a cryptorchid mouse testis is not hyperresponsive to hCG stimulation in vitro.

PMID- 1982289
TI  - Emotional processing and fear measurement synchrony as indicators of treatment
      outcome in fear of flying.
AB  - Minimal-therapist-involvement stress inoculation training was used to treat
      flying phobics. Relative to no-treatment controls, treatment subjects reported
      more fear reduction, were more likely to participate in an exposure session, and
      flew more during a two-month follow-up period. Subjects who exhibited synchronous
      changes in heart rate and report of anxiety during exposure had greater fear
      reduction than subjects showing less synchrony. Subjects who voluntarily took
      plane flights in the two months following treatment showed greater indications of
      emotional processing during in vivo exposure. Relative to flight avoiders, fliers
      had higher mean heart rate in the plane, a greater reduction in heart rate from
      the beginning to the end of the flight, and greater reported fear reduction from
      pre- to post-flight.

PMID- 1982291
TI  - ICAM-1 and LFA-1 expressions in the lesional skin of annular erythema associated
      with Sjogren syndrome.
AB  - ICAM-1 and LFA-1 expression was studied in the lesional skin of ten cases of
      annular erythema associated with Sjogren syndrome. Most of the infiltrating
      mononuclear cells around blood vessels expressed LFA-1 in addition to its strong
      expression on vascular endothelial cells and focal expression on the epidermal
      basal cell layer in 3 cases. ICAM-1 expression on vascular endothelial cells was
      similar to LFA-1, although relatively focal and weak expression was observed on
      mononuclear cells. ICAM-1 expression on keratinocytes was focal and limited to
      the basal cell layer in annular erythema. These findings suggest that strong
      expression of ICAM-1 on endothelial cells but not keratinocytes and LFA-1 on
      mononuclear cells might play some role in the induction of skin lesions in
      annular erythema associated with Sjogren syndrome.

PMID- 1982290
TI  - Situational exposure treatment versus panic control treatment for agoraphobia. A
      case study.
AB  - Situational in vivo exposure has been widely used in the treatment of
      agoraphobia. However, only a low to moderate proportion of individuals treated
      with this approach have shown a high level of therapeutic gain. The recent
      recognition of panic as central to the development and maintenance of a great
      many cases of agoraphobic avoidance suggests that treatments focused directly on
      panic may contribute to a more comprehensive approach to agoraphobia. The present
      single case demonstrates that whereas two modes of situational exposure produced
      only limited improvement an approach focused directly on panic had greater
      effectiveness. The specific effects of the treatment components within the panic
      control package are analyzed in detail.

PMID- 1982292
TI  - [Multiple forms of mammalian sialidase and their physiological significance].

PMID- 1982294
TI  - Nature of the mononuclear infiltrate and the mechanism of muscle damage in
      juvenile dermatomyositis and Duchenne muscular dystrophy.
AB  - Normal skeletal muscle does not express class I MHC antigens. In contrast, these
      antigens are strongly expressed at the periphery of muscle fibres in patients
      with juvenile dermatomyositis (JDM) and Duchenne muscular dystrophy (DMD).
      Interferons can induce the expression of class I antigens, but in this study
      interferon-gamma could not be detected in JDM muscle biopsy specimens using four
      different immunocytochemical techniques. However, an infiltrate of mononuclear
      cells capable of synthesising interferons was present in biopsies from JDM and
      DMD patients. The predominant cell types detected in both diseases were
      macrophages and T lymphocytes, these two cell types comprising more than 80% of
      the infiltrating mononuclear cells. A striking predominance of CD4+
      helper/inducer T cells was observed. The majority of these cells expressed class
      II MHC antigens and were, therefore, considered to be activated. Additional
      evidence for the functional activity of CD4+ T cells was derived from the finding
      that it was this population of cells from JDM biopsies which proliferated in
      response to interleukin-2 in vitro. T cell subsets in peripheral blood were also
      investigated in JDM and DMD patients. Only in the case of JDM were any
      significant differences from normal observed, where a significant reduction in
      the number of peripheral blood CD8+ T cells resulted in an elevation of
      CD4+/CD/8+ ratios. The role of CD4+ T cells and aberrant class I MHC antigen
      expression in mediating muscle damage in JDM and DMD is discussed.

PMID- 1982293
TI  - Mild brain atrophy in early HIV infection: the lack of association with cognitive
      deficits and HIV-specific intrathecal immune response.
AB  - Brain MRI and/or CT were performed on 72 HIV-infected patients at various stages
      of the disease, and on 34 controls. The neuroradiological findings were related
      to duration of the infection, neurological symptoms, and cognitive abnormalities
      as well as to immunological findings in the CSF and blood. All types of brain
      atrophy were more severe and more frequent in HIV-infected subjects than in
      controls. Patients with neurological symptoms, those with advanced HIV infection,
      and patients with a duration of HIV infection of more than 4 years showed the
      most severe and most frequent neuroradiological abnormalities, including central
      and cortical atrophy, brain stem atrophy, and cerebellar atrophy. Subjects with
      cognitive defects exhibited more severe central atrophy than cognitively intact
      patients. However, slight brain atrophy and/or parenchymal lesions were found in
      57% of cognitively intact HIV-seropositive individuals. Patients with brain
      atrophy and those with radiologically normal brain, both showed increased
      intrathecal synthesis of total IgG, and intrathecal HIV-antibody synthesis.
      However, a declined general immune response and a lowered CSF leukocyte count
      were seen predominantly in patients with brain atrophy. The results suggest that
      subcortical, neurologically "silent" areas of brain white matter are an early
      target of HIV infection.

PMID- 1982296
TI  - Evaluation of methodology for assessing release characteristics of
      thermosoftening vehicles.
AB  - Methodology has been devised for the testing and evaluation of the mechanistic
      release of drug or markers from thermosoftening materials, as represented by the
      Gelucire class of excipients, which could be predictive. Release of a drug
      (anhydrous theophylline) and a marker (D&C yellow No. 10) was determined using a
      calibrated stationary disc/rotating fluid system. Of the fourteen commercially
      available Gelucire excipients, six were investigated in detail (G46/07, G48/09,
      G50/02, G50/13, G53/10, G62/05) and found to have biphasic release profiles.
      Lipid soluble materials demonstrated predominantly diffusion-controlled release,
      while water-dispersible materials absorbed water and showed signs of swelling
      which led to erosion as an additional component of the release characteristics.

PMID- 1982295
TI  - Synthesis and pharmacological properties of nebivolol, a new antihypertensive
      compound.
AB  - The synthesis of alpha,alpha' (iminobis(methylene]-bis-(3,4-dihydro-2H
      1benzopyran-2-metha nol) derivatives and the stereochemistry and pharmacological
      profile of this new class of antihypertensive compounds are described. Finally,
      the selection and pharmacological profile of the preferred compound of this
      series, nebivolol and its enantiomers, is discussed.

PMID- 1982297
TI  - Pre- and post-junctional alpha-adrenoceptor-mediated responses in the rat gastric
      fundus in-vitro.
AB  - The effects of alpha 1- and alpha 2-adrenoceptor agonists on smooth muscle tone
      and on cholinergic excitatory and non-adrenergic, non-cholinergic inhibitory
      responses to field stimulation have been investigated in the rat gastric fundus
      in-vitro. None of the alpha-adrenoceptor agonists tested, noradrenaline,
      phenylephrine, cirazoline, guanoxabenz or UK-14,304 showed any contractile
      effects at concentrations up to 30 microM. In preparations where tone was raised
      by barium (0.5-2 mM), the mixed alpha 1- and alpha 2-adrenoceptor agonist
      noradrenaline (0.01-10 microM), and the selective alpha 1-adrenoceptor agonists
      cirazoline (0.01-10 microM) and phenylephrine (0.01-10 microM) produced
      concentration-dependent relaxations which were antagonized by the alpha 1
      adrenoceptor antagonist prazosin (0.01-1.0 microM). The selective alpha 2
      adrenoceptor agonists UK-14,304 (0.03-30 microM) and guanoxabenz (0.03-30
      microM), had no relaxant effects in raised tone. UK-14,304 (0.03-1.0 microM)
      produced a concentration-dependent inhibition of cholinergic nerve-induced
      responses which was antagonized by the alpha 2-adrenoceptor antagonist idazoxan
      (0.03-1.0 microM) but not by prazosin (0.03-1.0 microM). Noradrenaline (0.03-1.0
      microM) also produced an inhibition of cholinergic nerve-induced responses which
      was antagonized by idazoxan (0.03-1.0 microM). A small component of the
      noradrenaline inhibitory effects was antagonized by prazosin (10%). Cirazoline
      (0.03-1.0 microM) produced a small inhibition of cholinergic nerve-induced
      responses which was antagonized by prazosin (0.03-1.0 microM). The prazosin
      sensitive components of the inhibitory effects of noradrenaline and cirazoline
      occurred at concentrations which also produced post-junctional
      relaxation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1982298
TI  - Effect of recombinant human erythropoietin on new anaemic model rats induced by
      gentamicin.
AB  - The effects of recombinant human erythropoietin (r-HuEPO) on haematological
      parameters were studied in rats in which uraemia and anaemia had been induced by
      gentamicin, an aminoglycoside antibiotic and a nephrotoxic agent. After the
      occurrence of slight polycythaemia, the red blood cell count, haematocrit and
      haemoglobin concentration decreased by 20-30% compared with those of the control
      (saline-injected) rats. At the end of gentamicin treatment, the endogenous serum
      EPO level had decreased to about 40% compared with that of control rats.
      Gentamicin-treated rats showed marked elevation of blood urea nitrogen, extensive
      tubular necrosis in the kidney and haemosiderin deposition in the spleen. In the
      osmotic fragility test, the fragility of erythrocytes significantly increased
      compared with that of control rats. These findings indicate that the anaemia
      induced by gentamicin is due not only to a deficiency of EPO but also to an
      enhancement of fragility of erythrocytes in an azotaemic environment. The
      administration of r-HuEPO during anaemia markedly increased red blood cell count,
      haematocrit and haemoglobin concentration. It is suggested that a gentamicin
      treated rat is a useful and convenient anaemic model and r-HuEPO is useful for
      treatment of anaemia in acute renal failure.

PMID- 1982299
TI  - Impairment of endothelium-dependent relaxation and changes in levels of cyclic
      GMP in carotid arteries from stroke-prone spontaneously hypertensive rats.
AB  - Endothelium-dependent relaxation of carotid arteries and changes in levels of
      cyclic (c)GMP between stroke-prone spontaneously hypertensive (SHRSP) and Wistar
      Kyoto (WKY) rats have been compared. The concentration-response curve for
      acetylcholine (ACh)-induced relaxation was shifted to the right in carotid
      arteries from SHRSP. Relaxation responses produced by calcimycin (A 23187) and
      melittin, both endothelium-dependent agents, were depressed in carotid arteries
      from SHRSP. Relaxation responses produced by sodium nitroprusside and 8-Br-cGMP
      were similar to those in strips from WKY. ACh-induced production of cGMP was
      significantly decreased in carotid arteries from SHRSP when compared with the
      level for similarly treated strips from WKY. These results suggest that
      functional changes in endothelium, but not guanylate cyclase activity or cGMP
      sensitivity in the carotid arteries, may occur in hypertension. Thus, impaired
      endothelium-dependent relaxation in SHRSP may play an important role in
      hypertensive vascular diseases such as stroke.

PMID- 1982301
TI  - Alpha-adrenoceptor involvement in swim stress-induced antinociception in the
      mouse.
AB  - Three different intensities of swim stress produced stress-induced
      antinociception (SIA) in mice which was assessed either by the reduction in the
      number of abdominal constrictions produced by acetic acid or by an increase in
      reaction time on a hot-plate. The involvement of alpha-adrenoceptors in the three
      models of SIA was investigated using selective antagonists. SIA produced by the
      mild stress of a 30 s warm water swim was attenuated by idazoxan (0.5-1 mg kg-1),
      and by yohimbine at a dose (1 mg kg-1) which reduced antinociception produced by
      clonidine (12.5-50 micrograms kg-1). Indoramin (1-2 mg kg-1) did not affect this
      model of SIA, but reversed phenylephrine induced inhibition of the constrictions.
      A 3 min room temperature swim increased reaction times on the hot-plate and this
      naloxone-sensitive SIA was reduced significantly by prazosin (1-2 mg kg-1),
      idazoxan (0.5-1 mg kg-1) and yohimbine (0.5-1 mg kg-1) but enhanced by clonidine
      (0.5 mg kg-1) and noradrenaline (NA) (10 micrograms i.c.v.). Mice treated with 6
      hydroxydopamine (60 + 60 micrograms i.c.v.) were hypersensitive to the hot-plate
      and did not develop SIA. Levels of noradrenaline in the brain (minus the
      cerebellum) were decreased after the room temperature swim SIA. The most severe
      stress of a cold water swim produced SIA on the hot-plate which was initially
      naloxone-insensitive.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1982300
TI  - The possible mechanism of interaction between xanthines and quinolone.
AB  - To clarify the mechanism of interaction between theophylline and enoxacin, the
      effects of enoxacin and its metabolite, 4-oxo-enoxacin, on the disposition of new
      xanthine derivatives, 1-methyl-3-propylxanthine (MPX) and 3-propylxanthine
      (enprofylline), as models of theophylline have been investigated in rats.
      Pretreatment with enoxacin significantly delayed the elimination of MPX from
      plasma. No significant change in the volume of distribution of MPX was observed
      in the presence of enoxacin, but the total body clearance of MPX was
      significantly decreased by approximately 60 and 80% after pretreatment with 25
      and 100 mg kg-1 of enoxacin, respectively. The amount of the decrease in total
      body clearance depended on the dose of enoxacin. 4-Oxo-enoxacin had little or no
      effect on MPX disposition. A newly developed quinolone, NY-198, which does not
      affect the disposition of theophylline, also did not affect the disposition of
      MPX. Enoxacin also had no effect on the disposition of enprofylline. These
      results indicate that the mechanism for decrease in theophylline clearance
      induced by enoxacin may not be due to its metabolite, 4-oxo-enoxacin, but to
      enoxacin itself, and that enoxacin does not inhibit solely the elimination
      process depending on cytochrome P450 isoenzyme for N-demethylation. It is likely
      that enoxacin has no influence on the renal excretion of xanthines.

PMID- 1982302
TI  - Prevention by a Ginkgo biloba extract (GBE 761) of the dopaminergic neurotoxicity
      of MPTP.
AB  - In mice implanted subcutaneously with osmotic minipumps releasing the neurotoxic
      agent N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 7 days (105
      micrograms h-1/mouse) (approximately 100 mg kg-1 day-1) a significant reduction
      (approximately 25%) in the striatal dopaminergic nerve endings was observed. This
      neurotoxic effect was prevented by the semi-chronic ingestion of a Ginkgo biloba
      extract for 17 days (GBE 761, approximately 100 mg kg-1 day-1). The high
      concentrations (approximately 1 g L-1) at which GBE 761 in-vitro either prevented
      the uptake of [3H]dopamine by synaptosomes prepared from striatum, or prevented
      the specific binding of the pure dopamine uptake inhibitor [3H]GBR 12783 to
      membranes prepared from striatum suggests that the prevention of the MPTP
      neurotoxicity does not depend on an inhibition of the MPTP uptake by dopamine
      neurons. This is also suggested by the lack of prevention of the in-vitro
      striatal binding of [3H]GBR 12783 administered i.v. at a tracer dose, in mice
      pretreated for 8 days with GBE 761 (100 mg kg-1 p.o.) and receiving a
      supplementary gastric administration of GBE 761 (100 mg kg-1) 1 h before testing.
      Similar treatment with GBE 761 did not modify the toxicity for dopamine neurons
      of 6-hydroxydopamine (20 micrograms) directly injected into the striatum of rats.

PMID- 1982303
TI  - Cut-off effect in antimicrobial activity and in membrane perturbation efficiency
      of the homologous series of N,N-dimethylalkylamine oxides.
AB  - The antimicrobial activity of the homologous series of N,N-dimethylalkylamine
      oxides (DMAO) was found to be quasi parabolically dependent on alkyl chain length
      with a maximum at n approximately 15 and n approximately 12 for Staphylococcus
      aureus and Escherichia coli, respectively. The physiochemical properties of DMAOs
      as characterized by critical micelle concentrations, retention times of 1-alkenes
      generated from DMAOs by gas-liquid chromatography, Rm values in reversed phase
      chromatography, and bacterial lipid/aqueous phase partition coefficients were
      found to correlate with the alkyl chain length. The effect of DMAOs on the
      structure of the model membrane prepared from isolated lipids from Escherichia
      coli as detected by a spin probe method was maximal for the alkyl chain length n
      approximately 10-12 coinciding with the maximum in the antimicrobial activity
      observed with Escherichia coli. It is suggested that the cut-off in the DMAO
      antimicrobial activity is caused by the cut-off in the DMAO perturbing effect on
      the membrane structure.

PMID- 1982304
TI  - A disintegration test for vaginal tablets: comparison with BP test.
AB  - To improve the disintegration test for vaginal tablets described in the British
      Pharmacopoeia (BP), a monitoring apparatus was added, and tested with seven
      effervescent and five non-effervescent tablets. A tablet was placed on the metal
      disc of the BP disintegration apparatus, and the guided plate was placed on the
      tablet. The guided plate moved downward smoothly in a cylinder as the tablet
      disintegrated. The movement was recorded by using a kymograph. The end-point and
      process of disintegration of the tablet were automatically recorded and the
      results obtained suggest that the modified test is a useful tool for the quality
      control of vaginal tablets.

PMID- 1982305
TI  - Synthesis and resolution of the novel appetite suppressant 2-benzylmorpholine, a
      nonstimulant isomer of phenmetrazine.
AB  - The synthesis of 2-benzylmorpholine from allylbenzene together with its
      resolution into its (+)- and (-)-enantiomers is reported. Oral dosing of the
      racemate to dogs caused appetite suppression with an ED50 of 3 and 5.5 mg kg-1 at
      1 and 2 h, respectively, after access to a meat meal. No stimulant activity was
      observed in dogs given oral doses of 200 mg kg-1 but the appetite suppressant
      effect in dogs declined during 20 days of chronic oral dosing at 10 mg kg-1.
      Appetite suppression activity was shown to reside in the (+)-enantiomer.

PMID- 1982306
TI  - Phenytoin-bupropion interaction: effect on plasma phenytoin concentration in the
      rat.
AB  - The effect of coadministration of bupropion (50 mg kg-1, p.o.) on the disposition
      profile of phenytoin has been studied in the rat. Plasma phenytoin concentration
      was measured serially for 10 h by HPLC. Bupropion had little or no effect on the
      pharmacokinetic parameters of an acutely administered dose of phenytoin.
      Following multiple doses of phenytoin however (i.e. steady state) the
      coadministration of bupropion resulted in significant increases in the
      elimination half-life (t 1/2), the area under the plasma concentration-time curve
      (AUC) and the time to maximum plasma concentration (tmax). Allowing for the
      limitations of single dose studies, these results point to a possible
      pharmacokinetic interaction between bupropion and phenytoin--the clinical
      significance of which needs to be assessed.

PMID- 1982307
TI  - The effect of cigarette smoke on the plasma piroxicam concentrations in rats.
AB  - The plasma concentration of unchanged piroxicam has been determined at 15, 30, 60
      and 90 min after 10 mg kg-1 oral administration of the drug to rats exposed to
      cigarette smoke or pretreated with phenobarbitone, 3,4-benzpyrene or ethanol.
      Plasma piroxicam concentrations decreased in rats pretreated with phenobarbitone,
      3,4-benzpyrene and ethanol and in rats 24 h after exposure to cigarette smoke.

PMID- 1982308
TI  - The binding of physostigmine to human serum albumin.
AB  - The binding of [3H]physostigmine to crystallized human serum albumin (HSA) has
      been investigated using equilibrium dialysis. The percentage bound to 1% (w/v)
      HSA decreased from 18 to 4% as the total concentration of physostigmine increased
      from 3.3 nM to 2.7 microM (0.9 to 750 ng mL-1). A single class of specific
      binding sites with a large affinity constant, K = 8 x 10(7) L mol-1, was
      identified. The concentration of binding sites was approximately 3 nM. The
      Michaelis constants for human serum cholinesterase and albumin were the same; an
      explanation for these results is that the drug is binding to a trace
      cholinesterase, in the albumin.

PMID- 1982309
TI  - Plasma protein binding of disulfiram and its metabolite diethylthiocarbamic acid
      methyl ester.
AB  - The human plasma protein binding of disulfiram and its metabolite,
      diethylthiocarbamic acid methyl ester has been studied by an ultrafiltration
      technique. Both compounds were bound principally to albumin (mean 96.1 and 79.5%)
      over the ranges 200-800 and 345-2756 nM, respectively. The average number of
      binding sites was approximately 1 for both substances, whereas the average
      association constants were 7.1 x 10(4) and 6.1 x 10(3) M-1, respectively. Log P
      (octanol/water) was 2.81 for disulfiram and 1.85 for diethylthiocarbamic acid
      methyl ester.

PMID- 1982310
TI  - Susceptibility of bacterial isolates from AIDS patients to six fluoroquinolones.
AB  - The susceptibilities to ciprofloxacin, DR-3355 (S-(-)-ofloxacin), enoxacin,
      lomefloxacin, ofloxacin and PD127,391 of 69 significant bacterial isolates from
      HIV-positive patients at the City Hospital, Edinburgh have been determined. With
      the exception of the enterococci, most of the strains tested (including
      staphylococci, Escherichia coli and Pseudomonas aeruginosa) were susceptible to
      the fluoroquinolones. Ciprofloxacin was the most active of the clinically
      available drugs followed by ofloxacin, lomefloxacin and enoxacin. PD127,391 and
      DR-3355, the new fluoroquinolones tested, were at least as active as
      ciprofloxacin. Hence bacterial infections in AIDS patients should respond to
      fluoroquinolone therapy.

PMID- 1982311
TI  - The pharmacokinetics of artemisinin after oral, intramuscular and rectal
      administration to volunteers.
AB  - The pharmacokinetics after oral, intramuscular and rectal administration of
      artemisinin, a new potent antimalarial drug, to healthy volunteers has been
      examined. The study was set-up as a four-way cross-over design with a wash-out
      period of one week between the test days. In ten volunteers artemisinin
      concentrations in serum were monitored using a reversed phase HPLC assay with UV
      detection after derivatization. After oral administration, artemisinin was
      rapidly but incompletely absorbed, the mean absorption time was 0.78 h and the
      bioavailability relative to the intramuscularly injected suspension in oil 32%.
      The mean residence time of the latter (10.6 h) was 3 times that of the oral
      formulation (3.4 h). This seems to enable a twice daily dosage regimen for the
      intramuscular oil injection, while the oral formulation necessitates a more
      frequent dosing interval. After intramuscular injection and rectal administration
      of an aqueous suspension, very low and variable artemisinin concentrations in
      serum were observed, probably indicating a poor and erratic absorption.

PMID- 1982312
TI  - Influence of the method of fluosol-DA administration on antipyrine metabolism in
      the rat.
AB  - Antipyrine disposition has been determined in the rat following administration of
      Fluosol-DA by an intravenous infusion without blood removal or a haemodilution
      procedure, and compared with data from sham haemodiluted rats (blood removed and
      returned) and control rats which only received antipyrine. Antipyrine total body
      and renal clearance and the formation clearance of two of its metabolites were
      affected differently at 48 h by the pretreatments. The haemodilution procedure
      enhanced, the sham haemodilution reduced, and the intravenous infusion had no
      effect on the phenobarbitone inducible cytochrome P450 isoenzyme activity.

PMID- 1982313
TI  - Responses to excitatory amino acids of Purkinje cells' and neurones of the deep
      nuclei in cerebellar slice cultures.
AB  - 1. The actions of the endogenous excitatory amino acids (EAAS) glutamate (Glu),
      aspartate (Asp) and homocysteate (HCA) on Purkinje cells and neurones of the deep
      nuclei in cerebellar slice cultures were investigated using intracellular
      recordings in the single-electrode voltage-clamp mode and the whole-cell
      configuration of the patch-clamp technique. 2. Purkinje cells and neurones of
      deep cerebellar nuclei were identified according to their localization in the
      living cultures, their morphology as revealed by intracellular injections of
      Lucifer Yellow and their immunoreactivity to antibodies to the 28 kDa Ca2(+)
      binding protein. 3. When Purkinje cells were voltage-clamped near their resting
      membrane potential in a TTX-containing salt solution, Glu, Asp and HCA induced
      inward currents which were abolished by 6-cyano-7-nitroxaline-2,3-dione (CNQX), a
      selective antagonist of the non-N-methyl-D-aspartate (NMDA) subtype of EAA
      receptors. The selective antagonist of NMDA receptors, D-(-)-2-amino-5
      phosphonovaleric acid (D-APV), was ineffective in blocking the responses induced
      by these three amino acids. NMDA, even at high concentrations and in magnesium
      free bathing solution, had no detectable effect on membrane properties of
      Purkinje cells grown in culture during 11-34 days. 4. In magnesium-containing
      saline, the amplitude of the responses induced by Glu, Asp and HCA was a linear
      function of the membrane potential. 5. In contrast, neurones of the deep
      cerebellar nuclei were responsive to NMDA and the inward currents induced by Glu,
      Asp and HCA were partially blocked both by CNQX and by D-APV. 6. In magnesium
      containing saline, the amplitude of the currents induced by NMDA as well as by
      the three endogenous EAAs decreased at hyperpolarizing holding potentials whereas
      the current-voltage relation of the responses induced by quisqualate (QA) was
      strictly linear. 7. It is concluded that Purkinje cells in cerebellar slice
      cultures do not express NMDA receptors and that excitation of these neurones by
      the endogenous amino acids Glu, Asp and HCA is mediated exclusively through the
      activation of non-NMDA receptors. In the same preparation, neurones of the deep
      cerebellar nuclei possess NMDA and non-NMDA receptors which can be both activated
      by the three endogenous excitatory amino acids.

PMID- 1982314
TI  - Amino acid-mediated EPSPs at primary afferent synapses with substantia gelatinosa
      neurones in the rat spinal cord.
AB  - 1. Fast excitatory postsynaptic potentials (EPSPs) evoked by stimulation of A
      delta and C fibres were examined by intracellular recording from substantia
      gelatinosa (SG) neurones in a transverse slice preparation of adult rat spinal
      cord. 2. Single low-intensity stimuli applied to the dorsal root activated A
      delta fibres and evoked monosynaptic EPSPs in 70% of SG neurones. In 5% of SG
      neurones, increasing the intensity and duration of stimulation evoked solely C
      fibre-mediated EPSPs. About 20% of neurones received both A delta and C fibre
      input from primary afferents. 3. Low concentrations of tetrodotoxin (TTX,
      approximately 50 nM) blocked EPSPs evoked by stimulation of A delta fibres
      without affecting those evoked by C fibre stimulation. Higher concentrations of
      TTX (500 nM) also blocked C fibre-evoked responses. 4. EPSPs evoked by A delta
      and C fibre stimulation reversed in polarity at membrane potentials near 0 mV,
      similar to the reversal potential of spontaneous EPSPs and of the potential
      change evoked by exogenous glutamate. 5. A delta and C fibre-evoked EPSPs were
      depressed by kynurenate and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX); C fibre
      evoked EPSPs appeared to be less sensitive. 6. In the presence of TTX, only 50%
      of SG neurones were depolarized by L-glutamate. However, neurones which exhibited
      no direct response to L-glutamate received afferent-evoked EPSPs which were
      sensitive to CNQX. In sensitive neurones, the depolarization evoked by L
      glutamate was depressed by only approximately 15% in the presence of CNQX,
      whereas afferent-evoked EPSPs recorded from the same neurone were almost
      completely suppressed. Combined application of DL-2-amino-5-phosphonovaleric acid
      (APV) and CNQX depressed the response to L-glutamate by only approximately 25%.
      7. These findings suggest that A delta and C fibres use L-glutamate or a related
      amino acid as a transmitter at synapses with substantia gelatinosa neurones. The
      postsynaptic actions of this transmitter are mediated predominantly by non N
      methyl-D-aspartic acid (NMDA) receptors. The failure of CNQX and APV to
      completely block the L-glutamate-evoked depolarization of substantia gelatinosa
      neurones raises the possibility that exogenously applied L-glutamate activates a
      non-NMDA receptor distinct from that which mediates the actions of the
      synaptically released afferent transmitter.

PMID- 1982316
TI  - Restriction enzyme analysis of mitochondrial DNA of Acanthamoeba strains in
      Japan.
AB  - Eight isolates, identified as either Acanthamoeba castellanii or A. polyphaga
      from human eye infections, contact lens containers, and soil in Japan, were
      characterized by restriction fragment length polymorphisms (RFLP) of
      mitochondrial DNA (mtDNA). Mitochondrial DNA was digested with either Bgl II,
      EcoR I, Hind III, Hpa I, Sca I or Xba I, electrophoresed in agarose gels, and
      stained with ethidium bromide. Four distinct RFLP phenotypes that refer to the
      collection of six fragment size patterns obtained for a single strain with six
      enzymes, were discovered among the eight strains used in this study. Three
      strains morphologically classified as A. polyphaga share a single RFLP phenotype
      with the Ma strain of A. castellanii. The interspecific sequence differences of
      7.06-12.74% in DNA nucleotide were estimated from the proportion of DNA fragments
      shared by each pair of mtDNA.

PMID- 1982315
TI  - Properties of excitatory postsynaptic currents recorded in vitro from rat
      hippocampal interneurones.
AB  - 1. We studied excitatory synaptic currents activated by stimulation of Schaffer
      collateral-commissural fibres and recorded from interneurones in the CA1 region
      of hippocampal slices using whole-cell techniques. 2. Interneurones were
      identified by their location outside the cell layer and their morphology as seen
      with differential interference contrast (DIC) microscopy and by filling with
      Lucifer Yellow (LY). 3. The excitatory postsynaptic current (EPSC) had a fast,
      voltage-insensitive component and a slow component which had a region of negative
      slope resistance between -70 and -40 mV. The slow voltage-dependent component was
      abolished by the N-methyl-D-aspartate (NMDA) receptor antagonist (DL-2-amino-5
      phosphonovalerate (APV) 50 microM) which had little effect on the fast component.
      Conversely, the fast component was abolished by the non-NMDA receptor antagonist
      6-cyano-7-nitoquinoxaline-2,3-dione (CNQX; 10 microM), which had no effect on the
      slow component. 4. The rise time of the fast component ranged from 1 to 3 ms and
      the decay time constant ranged from 3 to 15 ms. The rise time of the slow
      component ranged from 5 to 11 ms and the decay time constant ranged from 50 to
      100 ms. 5. It is concluded that although the morphology of the excitatory
      synapses onto interneurones differs considerably from those onto pyramidal cells,
      their electrophysiological and pharmacological properties are very similar.

PMID- 1982317
TI  - Impact of H2-receptor antagonists on the outcome of treatment of perforated
      duodenal ulcer.
AB  - One hundred and eighty-five patients were perforated duodenal ulcer were treated
      at one hospital over the 21-year period which straddled the introduction of H2
      receptor antagonists. Of these 107 had simple closure, 58 simple closure with
      immediate H2-receptor antagonists and 20 immediate definitive surgery. The
      overall operative mortality rate was 5.4%. The rate of subsequent definitive
      surgery declined significantly in the years after the introduction of H2-receptor
      antagonists. Only a minority of those who came to subsequent definitive surgery
      had done so within the first year, the percentage rising from 16% at 1 year to
      43.7% at 10 years. Of the patients treated by simple closure alone, 44.3% had
      subsequent definitive surgery compared with 24.1% having H2-receptor antagonists
      in addition, but this difference was not statistically significant using life
      table analysis. Review of the 104 patients available in 1989 showed no
      significant differences in symptoms between the treatment groups. The only
      preoperative predictor of subsequent definitive operation was non-steroidal anti
      inflammatory drug consumption which showed a negative correlation. A 3-month
      history of dyspepsia before perforation did not predict the need for subsequent
      surgery. The symptomatic results in a different group of patients who had
      undergone highly selective vagotomy subsequent to a previous perforation were no
      different from patients treated by simple closure alone or with immediate
      prescription of H2-receptor antagonists. Bloating, however, was significantly
      more common after highly selective vagotomy. We believe that perforated duodenal
      ulcer should be treated by simple closure.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1982318
TI  - Orchidopexy: the younger the better?
AB  - The optimum age for orchidopexy in childhood remains controversial. Many believe
      that it should be performed before the child's second birthday, when irreversible
      changes occur in testicular morphology. Others have shown an increase in the risk
      of damage to the spermatic cord structures in early operation, resulting in
      gonadal atrophy. We reviewed 200 patients: 100 had had orchidopexy before and 100
      after their second birthday. From the case records and from long-term review, we
      found that 5% of the testes in each group became atrophic. Some testes, which
      were 'normal' at the 6-month review, had subsequently failed to increase in size,
      whereas some which were initially diagnosed as 'atrophic' had grown, by long-term
      follow-up to a similar, normal size compared with the contralateral organ. In the
      older group, we also found that 19 testes that had previously been diagnosed as
      having descended normally had ascended subsequently.

PMID- 1982320
TI  - [Diabetology--Japan in the World--from the 18th IDF Congress and recent diabetes
      journal].

PMID- 1982319
TI  - [Peripheral blood stem cell transplantation (PBSCT)].

PMID- 1982321
TI  - [Role of somatostatin carbohydrate metabolism system].

PMID- 1982322
TI  - [Clinical significance of urinary alanine aminopeptidase in diabetes mellitus].

PMID- 1982323
TI  - [Clinical significance of urinary glycyl-prolyl dipeptidyl aminopeptidase in
      diabetic nephropathies].

PMID- 1982324
TI  - [Role of glucagon in carbohydrate metabolism system].

PMID- 1982325
TI  - Sex difference in adrenergic receptor-mediated glycogenolysis in rat livers.
AB  - Catecholamine-induced stimulation of hepatic glycogenolysis in male and female
      rats was studied by detecting the cytosolic free Ca2+ concentration ([Ca2+]i),
      cAMP generation and adrenergic receptor function. Increase in alpha 1-adrenergic
      receptor-mediated [Ca2+]i and beta-adrenergic receptor-mediated cAMP generation
      were examined using isolated hepatocytes. No difference was found in the alpha 1
      adrenergic receptor-mediated response of [Ca2+]i in fura-2-loaded hepatocytes
      between males and females, while epinephrine-induced cAMP accumulation in
      hepatocytes was about 3-fold higher in females. The alpha 1- and beta-adrenergic
      receptor properties of the plasma membrane were evaluated by ligand binding
      studies using [3H]prazosin (alpha 1-adrenergic antagonist) and
      [125I]iodocyanopindolol (beta-adrenergic antagonist); and little sex difference
      was found in either affinity or the number of binding sites of [3H]prazosin and
      [125I]iodocyanopindolol. Activation of adenylate cyclase by forskolin and GTP
      gamma-S was also similar for both sexes. These results suggest that the sex
      difference of beta-adrenergic response is due to a difference in the guanine
      nucleotide regulatory binding proteins (G proteins) and/or beta-adrenergic
      receptor-Gs protein (the stimulatory G protein of adenylate cyclase) coupling
      ability.

PMID- 1982326
TI  - Binding profile of SM-9018, a novel antipsychotic candidate.
AB  - The present study employed various receptor-binding assays to clarify the
      biochemical characteristics of SM-9018. SM-9018 possessed very high affinity for
      5-HT2, D2 and 5-HT1A receptors (Ki = 0.61, 1.4 and 2.9 nM, respectively), and it
      had moderate affinity for alpha 1 and D1 receptors (Ki = 17 and 41 nM,
      respectively). However, SM-9018 had only negligible affinity for alpha 2, opiate,
      glutamate, phencyclidine, benzodiazepine and GABAA receptors. These results
      suggest that SM-9018 may be a novel antipsychotic agent with binding affinity for
      5-HT2 and 5-HT1A receptors.

PMID- 1982327
TI  - [Hypertrophic cardiomyopathy (clinical aspects, diagnosis and treatment)].

PMID- 1982328
TI  - [Postprandial lipid metabolism and atherosclerosis. International symposium.
      Frankfurt, 10 March 1990].

PMID- 1982329
TI  - [The indications for benzodiazepines in the treatment of insomnia].
AB  - We interviewed 219 patients with a questionnaire to evaluate the prevalence of
      insomnia, and to assess whether benzodiazepine therapy was correctly indicated.
      Insomnia was present in 86 patients (39%), being initial in more than one half.
      Thirty-two of the patients with insomnia were receiving benzodiazepines (37%), 24
      of whom (75%) had been treated for more than one year. The drug was incorrectly
      indicated in 18 (56%), in most cases because it was inappropriate for the type of
      the patient's insomnia. In six of these patients (33%), incorrect indication was
      related with self-medication. The benzodiazepine was incorrectly indicated in all
      the patients with diurnal oversedation. We emphasize the frequency of incorrect
      indications of these drugs, and we insist on the need that general practitioners
      have of a better knowledge of the pharmacokinetics of each drug, which is the
      basis for a correct indication.

PMID- 1982330
TI  - [A second drug in nonatopic asthma insufficiently controlled with beta 2
      adrenergic stimulants: budesonide versus theophylline].
AB  - We assessed whether theophylline or budesonide (an inhaled corticosteroid) is the
      most adequate drug to be added to the treatment of patients insufficiently
      controlled with beta agonists (procaterol). Two comparable groups of nonatopic
      asthmatic adults (n = 24), aged between 16 and 66 years (42 +/- 17), were
      investigated in a crossed, randomized study. After 4 weeks with procaterol + 800
      micrograms of budesonide, the forced expiratory flow improved (p less than 0.01),
      the degree of bronchial hyperreactivity to histamine was reduced (p less than
      0.001), the daily recorded symptomatology almost disappeared in all and the
      number of procaterol inhalations was reduced (p less than 0.05). The combination
      of theophylline + procaterol during 4 weeks did not improve these parameters from
      their baseline values. It was concluded that inhaled steroids are the drugs of
      choice in patients with asthma which is not controlled only with beta agonists.

PMID- 1982331
TI  - [Benzodiazepines and insomnia: should they always go together?].

PMID- 1982332
TI  - Antagonistic effects of growth hormone-releasing factor (GRF) and somatostatin on
      locomotor activity: GRF-induced hyperkinetic syndrome.
AB  - In order to investigate the potential antagonistic actions of the two main
      neuroregulators of the somatotropinergic system (GRF-SS-GH-SM axis), growth
      hormone-releasing factor (GRF) and somatostatin (SS) at the central level, the
      effects of GRF and SS on locomotor activity (LA) were studied in a computerized
      system. Male Wistar rats (N = 6-9 per group) received i.p. or i.c.v. GRF(1-44)NH2
      or SS(1-14) in doses ranging from 0.1-30 micrograms, and LA was automatically
      recorded in the OUCEM-86 system (Osaka University Computerized Electronic Maze)
      for 30-min periods. The peripheral administration of SS (1 microgram, i.p.) did
      not alter LA, while GRF (1 microgram, i.p.) increased LA from 20.35 +/- 4.18 to
      36.25 +/- 6.98 IO/min (p less than 0.005). After central injection, SS (1
      microgram; i.c.v.) decreased LA from 31.16 +/- 6.90 to 20.88 +/- 2.82 IO/min (p
      less than 0.005) and GRF (1 microgram, i.c.v.) increased LA to 47.60 +/- 5.35
      IO/min (p less than 0.005). SS- and GRF-induced LA changes were time- and dose
      dependent (SS: ED50 = 1.83 nmol, Emax = 6.10 nmol; GRF: ED50 = 99.1 pmol, Emax =
      1.98 nmol). The maximum effect of GRF appeared during the first 5 min, showing
      activity 10-15 sec post-injection, while the lowest activity induced by SS was
      registered 15-30 min after injection, although a significant reduction in LA was
      detected 5-10 sec after i.c.v. administration. With doses higher than 10
      micrograms (i.c.v.) SS provoked "barrel rotation", tremors and stereotyped
      behaviors. The GRF-induced hyperkinetic syndrome showed a linear pattern with
      doses up to 10 micrograms, and a plateau with 10-15 micrograms. Doses higher than
      20 micrograms induced convulsion, uncontrolled movements and a high death rate
      during the following 12-24 h. In conclusion, according to the present results,
      GRF and SS exert antagonistic effects on LA in a time- and dose-dependent manner,
      the former stimulating LA, and the latter inhibiting it.

PMID- 1982333
TI  - Down-regulation of squamous cell-specific markers by retinoids: transglutaminase
      type I and cholesterol sulfotransferase.

PMID- 1982334
TI  - Characterization of strains of Salmonella enterica subsp. enterica serovar Wien
      isolated in Italy: an epidemiological evaluation.
AB  - In the years 1987-1988, 110 strains of Wien serovar were isolated from a
      gastroenteritis outbreak in a neonatal unit in Palermo (Sicily). These strains
      showed different drug resistance patterns and plasmid profiles. Analysis of
      endonuclease restriction fragments of chromosomal DNA by hybridization with E.
      coli rRNA has demonstrated that a single bacterial clone or its derivatives were
      responsible for the outbreak. Furthermore, the study of 139 strains, isolated
      since 1970 from different geographic locations of the Mediterranean area, has
      confirmed a notable degree of homogeneity within Wien serovar, even though the
      detection of genetic polymorphisms in some isolates suggests that a number of
      distinct bacterial strains contributes to maintain the circulation of Wien
      serovar.

PMID- 1982335
TI  - [Further studies on the relationship between beta 2-agonists and hypokalemia in
      acute bronchial obstruction].

PMID- 1982336
TI  - Detection of DNA polymorphisms between two inbred mouse strains--limitations of
      restriction fragment length polymorphisms (RFLPs).
AB  - Type I (insulin-dependent) diabetes in humans is characterized by a T cell
      mediated destruction of insulin-secreting pancreatic beta cells. This autoimmune
      response is very similar to that seen in the non-obese diabetic (NOD) mouse
      strain. Originally bred from the ICR cataract-prone strain, NOD mice
      spontaneously develop T cell mediated insulitis and type I diabetes by the age of
      6 months. Backcross studies with the NOD mouse strain indicate segregation of at
      least three recessive genes. One of these, Iddm-1, has been shown to be tightly
      linked to the mouse MHC, H-2 on chromosome 17. Comparative studies with diabetic
      patients has also shown linkage to human HLA with protective and predisposing
      haplotypes being present within the population. In this study we have attempted
      to identify restriction fragment length polymorphisms (RFLPs) between the genomes
      of the NOD mouse strain and the diabetes-resistant strain C57BL/10. Such
      polymorphic loci will be used to screen DNAs from backcross animals that are
      diagnosed diabetic in an attempt to identify probes linked to the non-H2 disease
      susceptibility genes.

PMID- 1982337
TI  - Activation of postsynaptic striatal dopamine receptors, monitored by efflux of
      cAMP in vivo.
AB  - Intracerebral dialysis was used to monitor the change of extracellular
      concentration of striatal cAMP in rats anaesthetised with chloral hydrate.
      Forskolin (1-10 microM), an activator of adenylate cyclase, caused a
      concentration-dependent increase in efflux of cAMP, which was decreased by
      (+)PHNO (10 microM), an effect probably mediated by D2 sites, since (-)
      sulpiride, a D2 receptor antagonist prevented these effects. Dopamine (1-100
      microM) also increased the efflux of cAMP but only when the activity of monoamine
      oxidase and reuptake of dopamine were concomitantly blocked. The D1 receptor
      agonist SKF 38393 (1-100 microM) caused a concentration-dependent increase in
      efflux of cAMP, which was blocked by the D1 receptor antagonist SCH 23390 (1-100
      microM), but was unaffected by the D2 receptor antagonist sulpiride (10 microM)
      or by depletion of the concentration of striatal dopamine after pretreatment with
      6-hydroxydopamine. Taken together, these results indicate that intracerebral
      dialysis may be used to monitor the interaction of drugs with post-synaptic
      dopamine receptors in vivo.

PMID- 1982338
TI  - The effect of chronic administration of nicotine and withdrawal on somatostatin
      concentration and binding in brain of rat.
AB  - The effects of chronic administration of nicotine (20 or 30 days) and its
      withdrawal on somatostatin-like immunorectivity and the binding of 125I-Tyr11
      somatostatin in the frontoparietal cortex and hippocampus of the rat were
      investigated. Chronic administration of nicotine resulted in a decrease in the
      total number of specific somatostatin receptors, while the affinity of the
      receptors was unaltered and somatostatin-like immunoreactivity was unchanged in
      both areas of the brain. Three weeks after ending chronic exposure to nicotine in
      the second experimental group, the number of somatostatin receptors had returned
      to the same values as those of saline-treated rats.

PMID- 1982339
TI  - 6,7-Dinitroquinoxaline-2,3-dione and 6-nitro,7-cyanoquinoxaline-2,3-dione
      antagonize responses mediated by N-methyl-D-aspartate and NMDA-associated glycine
      recognition sites in vivo: measurements of cerebellar cyclic-GMP.
AB  - Direct intracerebellar administration of quisqualate resulted in marked increases
      in levels of cGMP in the cerebellum of the mouse, with a Hill number of 2.0.
      Quinoxalinediones, DNQX (6,7-dinitroquinoxaline-2,3-dione) and CNQX (6-nitro,7
      cyanoquinoxaline-2,3-dione) attenuated the quisqualate-induced response. 6,7
      Dinitroquinoxaline-2,3-dione also attenuated the D-serine-induced increases in
      levels of cGMP in a competitive manner. Intracerebellar injection of DNQX also
      antagonized the response to parenterally-administered harmaline. Similar results
      were also obtained with CNQX. These results indicate that these quinoxalinediones
      can attenuate the responses, mediated through the NMDA-associated glycine
      recognition sites, as well as the NMDA receptor complex. However, the glycine
      antagonist HA-966 (3-amino-1-hydroxypyrrolidone-2), at doses which completely
      reversed the increases induced by D-serine, failed to alter the response to
      quisqualate, indicating a lack of effect of glycine antagonists on quisqualate
      mediated synaptic events. These results further support the interaction of the
      quinoxalinediones, DNQX and CNQX, with the NMDA receptor complex as established
      in receptor binding and electrophysiological studies.

PMID- 1982340
TI  - Neurotensin attenuates dopamine D2 agonist quinpirole-induced inhibition of
      midbrain dopamine neurons.
AB  - The effects of intracerebroventricular (i.c.v.) administration of NT on the
      activity of midbrain DA neurons were studied in rats using single unit recording
      techniques. NT (i.c.v., 50 micrograms) was found to have no significant effect on
      the spontaneous activity of DA cells. On the other hand, NT treatment
      significantly attenuated the inhibitory effect of quinpirole (i.v.), a specific
      D2 agonist, on a subpopulation of DA cells. This result is consistent with
      previous behavioral and biochemical studies suggesting that NT may produce some
      of its effects through modulation of central DA systems.

PMID- 1982341
TI  - Diminished corticotropin and enhanced prolactin responses to 8-hydroxy-2(di-n
      propylamino)tetralin in methylenedioxymethamphetamine pretreated rats.
AB  - Although (+/-) methylenedioxymethamphetamine (MDMA) has been reported to deplete
      serotonin (5-HT) and destroy 5-HT terminals in the brains of animals, the
      functional sequelae of such alterations remain to be established. In the present
      study, a blunted corticotropin and an enhanced prolactin response to the 5-HT1A
      agonist 8-hydroxy-2(di-n-propylamino)tetralin (8-OH DPAT) was found in rats
      treated two weeks previously with a single dose of MDMA (2.0 or 20.0 mg/kg, sc).
      These results suggest that neurochemical changes produced by MDMA are associated
      with functional alterations as manifested by abnormal 5-HT receptor-coupled
      neuroendocrine responses.

PMID- 1982342
TI  - Microiontophoretic application of muramyl-dipeptide upon single cortical,
      hippocampal and hypothalamic neurons in rats.
AB  - Muramyl-dipeptide (MDP), a metabolite of bacterial cell walls, has a variety of
      biological effects, including the induction of acute phase serum glycoproteins
      and fever, and the promotion of slow wave sleep. Muramyl-dipeptide and other
      products, derived from immune responses, may act directly in the CNS to recruit
      secondary autonomic and endocrine responses to disease. To test this hypothesis
      the properties of single neuron discharges, following local application
      (microiontophoresis) of MDP within the somatosensory cortex, the dorsal
      hippocampus and the medial basal hypothalamus were studied in rats. The results
      obtained from cortical (N = 30), hippocampal (N = 28) and hypothalamic (N = 32)
      neurons demonstrated a direct effect of MDP upon all three regions of the brain.
      In addition, MDP modified the responses of these same neurons to morphine. These
      results support a role of MDP in the process of neuro-immune modulation and
      further demonstrate an interaction between lymphoid agents and opioids in the
      CNS.

PMID- 1982343
TI  - Effect of alpha2 antagonists and an agonist on EEG slowing induced by scopolamine
      and lesion of the nucleus basalis.
AB  - In the present study, the effects of an alpha 2 agonist (clonidine, 1.0 mg/kg
      i.p.) and two antagonists (atipamezole, 1 and 10 mg/kg s.c. and yohimbine, 3.0
      mg/kg i.p.) were studied on the EEG activity of naive rats, pretreated with
      either saline or scopolamine (0.8 mg/kg), or rats receiving lesioning of the
      nucleus basalis. The alpha 2 antagonists increased fast activity (alpha and
      beta). Clonidine increased slow wave activity (increased in spectral amplitudes)
      during periods of immobility and mobility. The EEG slowing, induced by
      scopolamine, was not alleviated by antipamezole or yohimbine, but in immobile
      rats, an increase in the delta and theta amplitudes was augmented by clonidine.
      In nucleus basalis-lesioned rats, the increase in delta activity was partially
      normalised by the alpha 2 antagonists. The decrease in the beta amplitude,
      induced by lesioning of the nucleus basalis, was not alleviated with either
      atipamezole or yohimbine. Clonidine increased the slow wave activity in nucleus
      basalis-lesioned rats and induced an increase in delta and theta bands during
      immobility. No changes were induced by clonidine in the EEG recorded from rats
      with lesions of the nucleus basalis.

PMID- 1982344
TI  - The glutamate-mediated release of dopamine in the rat striatum: further
      characterization of the dual excitatory-inhibitory function.
AB  - A push-pull cannula supplied with an artificial cerebrospinal fluid containing
      the tritiated precursor of dopamine, [3H]tyrosine, was implanted in the caudate
      nucleus of rats anesthetized with halothane. The extracellular dopamine and
      dihydroxyphenylacetic acid were measured in successive 20 min fractions (both in
      their tritiated and unlabeled form) and the ratio between the two forms
      calculated. Glutamate was added to the superfusing cerebrospinal fluid to
      investigate its role in the process of dopamine release. The release of dopamine
      and the efflux of dihydroxyphenylacetic acid were activated by a low
      concentration (10(-8) M) of glutamate. In contrast, a higher concentration (10(
      4) M) of the amino acid reduced the release of dopamine. These results first
      confirmed the presence of a dual mechanism of control, by glutamate, of the
      dopamine release in the striatum depending on the extracellular concentration.
      Secondly, these treatments affected the dihydroxyphenylacetic acid amount and
      predominantly the tritiated form of dopamine, suggesting that the glutamate
      induces an important increase of the amine synthesis, in spite of a moderate
      effect on the release. The reversal of the inhibition by applications of
      tetrodotoxin (5 x 10(-7) M) and bicuculline (10(-4) M) confirmed that it was
      mediated by an indirect mechanism involving a GABAergic neurotransmission. In
      addition, the increase of the spontaneous dopamine release during bicuculline
      application suggested the existence of a tonic mechanism of inhibition of
      dopamine release in the striatum. This was confirmed by the fact that local
      xylocaine-induced anesthesia of the sensory motor cortex increased the
      spontaneous release of dopamine in the striatum.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1982345
TI  - Striatal opiate mu-receptors are not located on dopamine nerve endings in the
      rat.
AB  - In rat striatal slices, the autoradiographic analysis of [3H]naloxone binding
      allows one to define highly labelled patches corresponding to the striosomes and
      representing about 17% of the total striatal volume, surrounded by a poorly
      labelled zone, the matrix. Previous studies have shown that the density of these
      mu-opiate receptor binding sites is decreased by about 28% following destruction
      of the striatal dopamine innervation suggesting a partial localization of these
      receptors on dopamine presynaptic nerve endings. These results were confirmed
      but, in addition, we have shown that a chronic (30 days) blockade of dopamine
      transmission obtained by treatment of the animals with a long acting neuroleptic
      induces a similar decrease of mu binding sites. Further experiments made with D
      Pen2,D-Pen5-[tyrosyl-3-5(n)-3H] enkephalin, a selective delta opiate receptor
      agonist, have revealed that the density of delta opiate binding sites is
      decreased (30%) in rats with striatal dopamine denervation but not in those
      treated with the long acting neuroleptic. These data indicate that part of these
      delta receptors is located on dopamine nerve terminals but are not in favour of
      the presence of mu receptors on these nerve terminals. The decrease in
      [3H]naloxone binding sites induced by prolonged interruption of dopamine
      transmission can be attributed to postsynaptic events.

PMID- 1982346
TI  - N-methyl-D-aspartate, kainate and quisqualate release endogenous adenosine from
      rat cortical slices.
AB  - N-Methyl-D-aspartate, kainate, and quisqualate released endogenous adenosine from
      superfused slices of rat parietal cortex. N-Methyl-D-aspartate-evoked adenosine
      release was blocked by D,L-2-amino-5-phosphono-valeric acid and (+)-5-methyl
      10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK-801),
      indicating that it was receptor-mediated, although it did not show the expected
      potentiation in the absence of Mg2+. In contrast, N-methyl-D-aspartate-evoked
      release of [3H]noradrenaline from the same slices was markedly potentiated in
      Mg2(+)-free medium. Therefore, the lack of Mg2+ modulation of N-methyl-D
      aspartate-evoked adenosine release was not due to depolarization-induced
      alleviation of the Mg2+ block in the slices. Kainate-evoked adenosine release was
      diminished by the non-specific excitatory amino acid antagonist, gamma-D-glutamyl
      glycine, and kainate- and quisqualate-evoked adenosine release was diminished by
      6,7-dinitroquinoxaline-2,3-dione, indicating that these agonists release
      adenosine by acting at non-N-methyl-D-aspartate receptors. Tetrodotoxin decreased
      N-methyl-D-aspartate- and kainate-evoked adenosine release by 40% and 19%
      respectively, indicating that release was mediated in part by propagated action
      potentials in the slices. Total release of adenosine by N-methyl-D-aspartate,
      kainate or quisqualate was not diminished in the absence of Ca2+. A second
      exposure to kainate following restoration of Ca2+ to slices previously
      depolarized in the absence of Ca2+ resulted in an amount of adenosine release
      equal to an initial release by slices in the presence of Ca2+, a result
      suggesting the presence of separate Ca2(+)-dependent and Ca2(+)-independent pools
      of adenosine. The present experiments demonstrate that activation of all three
      major subtypes of excitatory amino acid receptors in the cortex releases
      adenosine, possibly from separate Ca2(+)-dependent and -independent pools.
      Adenosine released from the cortex following excitatory amino acid stimulation
      may, by acting at inhibitory P1 purinoceptors, diminish excitatory
      neurotransmission and protect against excitotoxicity.

PMID- 1982347
TI  - A novel behavioral model of neuropathic pain disorders produced in rats by
      partial sciatic nerve injury.
AB  - Partial nerve injury is the main cause of causalgiform pain disorders in humans.
      We present here a novel animal model of this condition. In rats we unilaterally
      ligated about half of the sciatic nerve high in the thigh. Within a few hours
      after the operation, and for several months thereafter, the rats developed
      guarding behavior of the ipsilateral hind paw and licked it often, suggesting the
      possibility of spontaneous pain. The plantar surface of the foot was evenly
      hyperesthetic to non-noxious and noxious stimuli. None of the rats autotomized.
      There was a sharp decrease in the withdrawal thresholds bilaterally in response
      to repetitive Von Frey hair stimulation at the plantar side. After a series of
      such stimuli in the operated side, light touch elicited aversive responses,
      suggesting allodynia to touch. The withdrawal thresholds to CO2 laser heat pulses
      were markedly lowered bilaterally. Suprathreshold noxious heat pulses elicited
      exaggerated responses unilaterally, suggesting thermal hyperalgesia. Pin-prick
      evoked such exaggerated responses bilaterally (mechanical hyperalgesia). In a
      companion report, we show that these abnormalities critically depend on the
      sympathetic outflow. Based on the immediate onset and long-lasting perpetuation
      of similar symptoms, such as touch-evoked allodynia and hyperalgesia, and the
      resemblance of the contralateral phenomena to 'mirror image' pains in some humans
      with causalgia, we suggest that this preparation may serve as a model for
      syndromes of the causalgiform variety that are triggered by partial nerve injury
      and maintained by sympathetic activity.

PMID- 1982348
TI  - The maturation of the somatostatin systems in the rat visual cortex.
AB  - The development of somatostatin-immunoreactive (SS) neurons and processes in the
      rat visual cortex (VC) was studied in animals from embryonic day 20 (E20) to
      postnatal day 21 (D21). Three distinct patterns of immunoreactivity were seen.
      From E20 to birth (D0), VC was characterized by a small number of mainly bipolar
      SS neurons throughout the cortical plate. In the perinatal period, from D1 to D6,
      there were large numbers of immature immunoreactive neurons which were confined
      to layer VI and the subplate zone, a few bipolar neurons in the cortical plate
      and an extremely dense plexus of SS processes throughout the neuropil. The third
      phase, from D8 to weaning, was characterized by the absence of immature SS
      neurons, an increase in the number of multipolar SS neurons and a decrease in the
      density of SS fibers. By D15, the time of eye-opening, the number and
      distribution of SS neurons and processes was close to that seen in the adult.
      These results indicate that the SS system of neurons and fibers is among the
      earliest of the transmitter systems to be established in VC and suggests a role
      for the peptide in cortical organization as well as visual processing.

PMID- 1982349
TI  - Regulation of TRH release by the cultured neonate rat pancreas.
AB  - The TRH secretory responsiveness of the pancreatic islet cell clusters from
      newborn rat in organ culture was studied. Basal TRH secretion was stable over a 9
      day period. The response to various secretagogues was tested on day 4. TRH
      secretion was stimulated by high potassium-induced depolarization and also
      through both cAMP and protein kinase-C dependent pathways. Like insulin, TRH
      release was stimulated by glucose and arginine and inhibited by somatostatin.
      These data suggest the existence of a common mechanism for TRH and insulin
      secretion by the pancreatic beta-cells.

PMID- 1982350
TI  - Somatostatin binding to dissociated cells from rat cerebral cortex.
AB  - A method has been developed for the study of somatostatin (SS) binding to
      dissociated cells from rat cerebral cortex. Binding of [125I] [Tyr11]SS to cells
      obtained by mechanical dissociation of rat cerebral cortex was dependent on time
      and temperature, saturable, reversible and highly specific. Under conditions of
      equilibrium, i.e., 60 min at 25 degrees C, native SS inhibited tracer binding in
      a dose-dependent manner. The Scatchard analysis of binding data was linear and
      yielded a dissociation constant of 0.60 +/- 0.08 nM with a maximal binding
      capacity of 160 +/- 16 fmol/mg protein. The binding of [125I] [Tyr11]SS was
      specific as shown in experiments on tracer displacement by the native peptides,
      SS analogues, and unrelated peptides.

PMID- 1982351
TI  - Ultrastructural demonstration of synaptic connections between calcitonin gene
      related peptide immunoreactive axons and dynorphin A(1-8) immunoreactive dorsal
      horn neurons in a rat model of peripheral inflammation and hyperalgesia.
AB  - Synaptic contact between dynorphin A(1-8)-like immunoreactive lamina V spinal
      neurons and calcitonin gene-related peptide-like immunoreactive axon terminals
      was demonstrated using the immuno-electron microscopic mirror technique in a rat
      model of peripheral inflammation and hyperalgesia. Adjacent tissue sections were
      immunocytochemically labeled for either dynorphin A(1-8) or calcitonin gene
      related peptide and examined at the electron microscopic level for the presence
      of synaptic contacts. The results suggest that some opioid neurons which exhibit
      a dynamic increase in dynorphin peptide associated with peripheral inflammation
      and hyperalgesia receive direct monosynaptic input from presumptive nociceptive
      primary afferents.

PMID- 1982352
TI  - Effect of caerulein on decreased latency of passive avoidance response in rats
      treated with NMDA receptor antagonists.
AB  - The effect of subcutaneous injection of caerulein on memory impairment induced by
      intracerebroventricular administration of NMDA receptor antagonists was examined
      in the passive avoidance response of the rat. When rats were treated with AP5,
      AP7, CPP or MK-801, the retention latencies decreased markedly. However, in rats
      that received caerulein immediately after the training trials, the latency
      increased to some extent. Pretreatment with caerulein and subsequent injection of
      the competitive NMDA receptor antagonists AP5, AP7 and CPP caused a more apparent
      increase in the latency. The noncompetitive NMDA receptor antagonist MK-801 was
      not affected by pretreatment with caerulein. The difference might be, at least in
      part, due to the sites of action of these NMDA receptor antagonists.

PMID- 1982353
TI  - Molecular analysis of endogenous virus ev21-slow feathering complex of chickens.
      1. Cloning of proviral-cell junction fragment and unoccupied integration site.
AB  - Sex-linked slow-feathering gene, K, is genetically associated with the presence
      of an avian endogenous retrovirus ev21 in White Leghorns (WL). An EcoRI fragment
      corresponding to the endogenous virus ev21-cell junction fragment and a fragment
      homologous to the proviral unoccupied site (US) were cloned, respectively, from
      genomic DNA libraries of two WL chickens: an ev21-only female and an ev-negative
      male. A 1.7-kilobase pairs (kbp) fragment cleaved from the cloned proviral US by
      the HaeIII restriction endonuclease was the most informative probe to molecularly
      characterize the occupied and unoccupied integration sites of ev21 locus.
      Restriction fragment length polymorphism analysis of slow-feathering (SF) and
      rapid-feathering (RF) chickens from various commercial breeds, using the US
      HaeIII 1.7-kbp probe, indicated that the complete genetic association between
      ev21 and SF phenotype is common among other lines of SF chickens and was not
      restricted to WL. It was also shown that there was at least one additional DNA
      region highly homologous to DNA sequences flanking the EV21 integration site in
      the chicken genome. In SF birds of either sex this additional repeat was
      distinguishable from the site occupied by ev21 (OR) and represents an unoccupied
      repeat (UR). Analysis of DNA from RF revertant females showed novel patterns of
      reversion. In Type I RF revertants, RF is associated with the complete excision
      of proviral ev21 DNA sequences. In Type II revertants, the UR homologous to the
      cell sequences flanking ev21 integration site is excised, but proviral ev21
      sequences remain intact. A hypothesis to explain these types of reversion is
      suggested. It postulates a close association between OR and UR on the Z
      chromosome.

PMID- 1982354
TI  - Unilateral injections of a D2 but not D1 agonist into the frontal cortex of rats
      produce a contralateral directional bias.
AB  - Unilateral manipulations of frontocortical dopamine have been found in previous
      studies to produce a directional bias in the circling behaviour of rats. Agonists
      produced contralateral circling and antagonists produced ipsilateral turning. To
      examine the role of dopamine receptor subtypes, the present studies investigated
      the ability of unilateral intrafrontal cortical microinjections of the D1
      agonist, SKF 38393 or the D2 agonist, quinpirole to produce contralateral
      circling in rats. The antagonist, cis-flupenthixol was also tested and was
      expected to produce ipsilateral circling. In 3 separate experiments, rats
      received 7 50-min sessions in a circular arena separated by at least 48 hr. The
      first and final sessions were preceded by no injection, the second and sixth by
      saline [or the inactive trans isomer (2.5 micrograms) in the flupenthixol
      experiment] and the middle 3 sessions by doses of cis-flupenthixol (1, 10, 25
      micrograms in 0.5 microliter), quinpirole (3, 6, 12 micrograms) or SKF 38393 (2,
      4, 8 micrograms), the order being counterbalanced across rats. cis-Flupenthixol
      and quinpirole produced dose-dependent ipsi- and contralateral circling,
      respectively, whereas SKF 38393 was without significant effect. No reliable
      directional bias was seen in any no-injection, saline or trans-flupenthixol
      sessions. Results suggested that the D2 receptor may mediate the motor effects of
      frontal cortical dopamine.

PMID- 1982355
TI  - A comparison of benzodiazepine, serotonin, and dopamine agents in the taste
      reactivity paradigm.
AB  - Previous studies have shown that rats' positive, palatability-dependent
      consummatory reactions to infused tastes are selectively facilitated by a
      benzodiazepine agonist (chlordiazepoxide), and that this effect can be blocked by
      the coadministration of benzodiazepine antagonists (e.g., Ro 15-1788). The
      purpose of the present study was to determine whether agents acting at other
      receptor sites (dopaminergic, serotonergic), which have been shown to modulate
      food consumption, might also modify rats' palatability-dependent reactivity to
      infused tastes. In this experiment, the benzodiazepine agonist, diazepam,
      facilitated positive palatability reactions, while dopaminergic agents
      (haloperidol, apomorphine, amphetamine) had no significant effects on either
      positive or aversive reactions. The putative 5-HT1A agonists, buspirone and
      gepirone, had a general inhibitory action on both positive and aversive
      palatability reactions. These results are surprising in view of the effects of
      serotonergic and dopaminergic agents on food and fluid intake. Our results
      suggest that the benzodiazepine receptor system may play a special role in the
      neural control of appetite through its enhancement of the positive palatability
      of tastes. Dopamine systems, by contrast, appear to control food intake by
      modulating processes that are independent of food affect evaluation.

PMID- 1982356
TI  - Benzodiazepine-induced antagonism of opioid antinociception may be abolished by
      spinalization or blockade of the benzodiazepine receptor.
AB  - The mechanisms underlying benzodiazepine antagonism of opioid antinociception
      were studied using the tail flick test and the hot plate test in mice. Both
      single-dose and repeated diazepam treatment antagonized the antinociceptive
      effect of morphine. The specific benzodiazepine antagonist flumazenil completely
      reversed the antagonism between diazepam and morphine. Mid-thoracic spinalization
      also abolished the antagonism, indicating that the antagonism takes place at
      higher levels in the CNS. Neither diazepam nor midazolam showed any affinity for
      opioid mu or kappa receptors in membranes prepared from mouse forebrain. Taken
      together with the results of other studies of interactions between GABAergic
      drugs and opioids, the results indicate that a benzodiazepine receptor-mediated
      mechanism at higher levels in the CNS, possibly in the brainstem, blocks the
      effect of opioids on nociceptive transmission.

PMID- 1982357
TI  - Demonstration of cell types among cone bipolar neurons of cat retina.
AB  - We identified all the cone bipolar cells (80) in a small patch of one retina and
      then studied in detail the complete subset (42) that sends axons to sublamina b
      of the inner plexiform layer. The point was to learn whether the 'types'
      suggested previously, based on a few examples from a large population, could be
      substantiated or whether there would be intermediate forms. Tissue from the area
      centralis (1 degree eccentricity), was prepared as a series of 279 ultrathin
      sections and photographed in the electron microscope. Thirteen cells were
      reconstructed completely and parcelled into five categories (b1-b5) based on
      external morphology. For nine of these cells (two from categories b1-b4 and one
      from b5) most of the synaptic inputs and outputs were identified. When these nine
      cells were parcelled according to their synaptic patterns, they sorted into the
      same five categories. The remaining 29 cells in the population, though not
      reconstructed, were studied in detail by tracing their processes through the
      series. Ten of these cells, those near the margin of the series, were incomplete.
      The other 19 cells had essentially the same distribution of morphologies and
      synaptic patterns as the subset studied by total reconstruction: when plotted in
      multiparametric space, they formed distinct clusters corresponding to the five
      morphological categories. There was no hint of intermediate forms. That all the
      neurons in the population sort into some cluster (no intermediate forms), and
      that each neuron sorts into the same cluster by different criteria, argues that
      the clusters represent natural types. Each type forms a regular array in the
      region studied with an axonal 'coverage factor' that is close to one.

PMID- 1982358
TI  - Convergence and divergence of cones onto bipolar cells in the central area of cat
      retina.
AB  - In the central area of cat retina the cone bipolar cells that innervate sublamina
      b of the inner plexiform layer comprise five types, four with narrow dendritic
      fields and one with a wide dendritic field. This was shown in the preceding paper
      (Cohen & Sterling 1990 a) by reconstruction from electron micrographs of serial
      sections. Here we show by further analysis of the same material that the coverage
      factor (dendritic spread x cell density) is about one for each of the narrow
      field types (b1, b2, and b4). The same is probably true for the other narrow
      field type (b3), but this could not be proved because its dendrites were too fine
      to trace. The dendrites of types b1, b2, and b4 collect from all the cone
      pedicles within their reach and do not bypass local pedicles in favour of more
      distant ones. The dendrites of type b5, the wide-field cell, bypass many
      pedicles. On average 5.1 +/- 1.0 pedicles coverage on a b1 bipolar cell; 6.0 +/-
      1.2 converge on a b2 cell and 5.7 +/- 1.5 converge on a b4 cell. Divergence
      within a type is minimal: one pedicle contacts only 1.2 b1 cells, 1.0 b2 cells,
      and 1.0 b4 cells. Divergence across types is broad: each pedicle apparently
      contacts all four types of the narrow-field bipolar cells that innervate
      sublamina b. Each pedicle probably also contacts an additional 4-5 types of
      narrow-field bipolar cell that innervate sublamina a. There are several possible
      advantages to encoding the cone signal into multiple, parallel, narrow-field
      pathways.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1982359
TI  - Determinants and consequences of eating and drinking. Paris, France, July 4-8,
      1989.

PMID- 1982360
TI  - Effects of intracerebroventricular injection of dynorphin, leumorphin and alpha
      neo-endorphin on operant feeding in pigs.
AB  - Young pigs, which are useful experimental animals for biomedical research, were
      prepared with lateral intracerebroventricular (ICV) cannulae and housed
      individually in cages fitted with operant panels, with food and water ad lib. ICV
      injection of 200 micrograms of dynorphin A 1-17 or 1-13 resulted in a significant
      meal commencing within 2-5 min. Shorter fragments of dynorphin (1-10, 1-9, 1-8)
      were ineffective at inducing feeding as was dynorphin B (rimorphin). In the same
      situation, leumorphin and alpha neo-endorphin (200 micrograms) elicited
      significant feeding but beta neo-endorphin did not. Dynorphin 1-17 or 1-13,
      administered 5 min before feeding started, increased meal size when pigs were fed
      after 4-h deprivation. Naloxone ICV (0.4 mg) significantly reduced food intake in
      pigs feeding after 4-h deprivation and its main effect was in the second half of
      the meal. Naloxone also abolished the effect of ICV dynorphin. It is concluded
      that dynorphin and related endogenous opioids are involved in the regulation of
      food intake in pigs.

PMID- 1982361
TI  - Multiple cholecystokinin (CCK) receptors and CCK-monoamine interactions are
      instrumental in the control of feeding.
AB  - Almost two decades ago, exogenous cholecystokinin (CCK) was shown to suppress
      food consumption in rats. Since then, CCK has been detected not only in
      peripheral tissue but extensively throughout the central nervous system.
      Furthermore, specific CCK receptors have been described, and a distinction drawn
      between CCK-A and CCK-B receptors. Recently, potent, orally active CCK
      antagonists, which show a high degree of selectivity for either CCK-A or CCK-B
      receptors, have been introduced. The present report reviews recent evidence
      obtained in studies using devazepide (a selective CCK-A receptor antagonist) and
      L-365,260 (a selective CCK-B/gastrin receptor antagonist). Both compounds
      increased food consumption and postponed the onset of satiety in well-satiated
      rats. L-365,260 was more potent, suggesting that central CCK-B type receptors may
      mediate the satiety effects of endogenously released CCK. Only devazepide was
      effective in blocking the feeding-suppressant effect of exogenous CCK, indicating
      that CCK-A type receptors mediate this effect. In a second series of studies,
      devazepide but not L-365,260 antagonized the anorectic effect of either d
      fenfluramine or systemically administered 5-HT. Hence, CCK-A type receptors
      appear to be involved in the anorectic effects of these serotonergic drugs. We
      propose that CCK and 5-HT mechanisms involved in mediating satiety are mutually
      interdependent. Possible interactions between CCK and catecholaminergic
      mechanisms are also briefly considered.

PMID- 1982362
TI  - [Changes in the diagnosis and treatment of borderline personality disorder at the
      Fukuoka University Hospital].

PMID- 1982363
TI  - Molecular and cellular mechanisms of neuronal plasticity in normal aging and
      Alzheimer's disease. Presentations made at the National Institute on Aging
      symposium. May 3, 1989, Bethesda, Maryland.

PMID- 1982364
TI  - Integration by the neuronal growth cone: a continuum from neuroplasticity to
      neuropathology.

PMID- 1982365
TI  - Intracortical processes regulating the integration of sensory information.
AB  - The mechanisms that link sensory inputs in spatially separated regions of cortex
      can be elucidated by analyzing the mechanisms that generate receptive field
      properties in cortical neurons under conditions that mimic the waking state; a
      state when learning, memory and the modification of synaptic strength can be most
      readily demonstrated. Important advances in understanding receptive field
      mechanisms in sensory cortex have arisen from studying the precise relationship
      between the mystacial vibrissae or "whiskers" and their neural representation in
      separate cortical domains or "barrels". The anatomical precision of whisker
      projections to barrels permits a unique delineation of thalamocortical and
      intracortical components of cortical cell responses based on latency and security
      of response to peripheral receptor stimulation. When recorded in awake animals or
      even under very light anesthesia, cortical neurons show two components to their
      response to whisker movement. Neurons in layer IV of a whisker's primary
      projection zone respond with short latency (7-10 msec) and a high response
      magnitude (two or more action potentials (spikes) per stimulus). This "Center
      Receptive Field" (CRF) for layer IV cells is generated in large part by sensory
      fiber inputs from the thalamus. The CRF is restricted to 1.4 whiskers on average
      and is the only response detectable when cortical responses are depressed by deep
      anesthesia. In the "waking state" the same neuron often will respond to
      deflection of 4-6 surrounding whiskers, but only at longer latency (15-40 msec)
      and with fewer spikes per stimulus. These more labile responses form an
      excitatory surround receptive field (SRF). Sensory information that is transduced
      by individual whiskers and that generates the SRF of a cortical neuron achieves
      this added response complexity through intracortical mechanisms. The control of
      the mechanisms that determine the dissemination of sensory information within
      cortex include: (1) regulating the level of GABAergic inhibition; and (2)
      potentiation or depression of the response level generated by repeated sensory
      experience. State-dependent "modulatory" inputs to cortex, such as the
      noradrenergic and cholinergic fiber system, could regulate the degree of
      horizontal spread of a sensory input, in part through global changes in the level
      of inhibition and/or regulating the amplitude of cortical responses, thereby
      determining the level of associative interactions between sensory inputs.

PMID- 1982366
TI  - Glucocorticoids, hippocampal damage and the glutamatergic synapse.

PMID- 1982367
TI  - Nerve growth factor induces gene expression of the prion protein and beta-amyloid
      protein precursor in the developing hamster central nervous system.

PMID- 1982368
TI  - Excitotoxin-mediated neuron death in youth and old age.
AB  - Here I have discussed current issues in excitotoxicology (neurotoxicity of Glu
      and related agents) with special emphasis on the NMDA receptor and its possible
      role in neuropsychiatric disorders. I have briefly described several classes of
      anti-excitotoxic agents which are currently under study for their ability to
      protect neurons against excitotoxin-mediated neuronal degeneration. There is
      growing interest in the possibility that such agents, especially NMDA antagonists
      will prove useful in the clinical management of neurodegenerative disorders;
      however, neither their efficacy nor safety has been adequately established at
      present. With the plethora of new information about the NMDA receptor--ionophore
      complex, one tends to forget that non-NMDA receptors can also mediate excitotoxic
      events. Thus, although we know less about the physiology and make up of non-NMDA
      receptors, it seems likely that new information, as it becomes available, will
      reveal new links between endogenous excitotoxins and neuropsychiatric disease
      processes. In particular, since NMDA receptors are relatively more sensitive in
      early life and non-NMDA receptors more sensitive in adulthood, it is reasonable
      to postulate the greatest involvement of the former in developmental
      psychoneuropathology and the latter in neurodegenerative diseases of the elderly.

PMID- 1982369
TI  - Neurono-glial interactions and neural plasticity.

PMID- 1982370
TI  - Widowhood and anxiety.

PMID- 1982371
TI  - Haemorrhagic fever with renal syndrome: evaluation of ELISA for detection of
      Puumala-virus-specific IgG and IgM.
AB  - IgM and IgG ELISA to Puumala virus were evaluated using sera from patients with
      haemorrhagic fever with renal syndrome (HFRS) from different geographical
      regions: Sweden, Denmark, Norway, Belgium and the European USSR. IgM ELISA proved
      useful in the diagnosis of HFRS in patients from all the regions mentioned above.
      Specific IgM could be detected as early as day 1 post onset of disease, and
      patients remained IgM-positive for several months. Specific IgG ELISA antibodies
      were also frequently detected in acute sera, and acute-convalescent serum pairs
      often failed to show a significant titre rise or increase in optical density (OD)
      values. This limits the use of IgG ELISA in patient diagnosis. Sera collected 2
      years after infection revealed higher IgG ELISA OD readings than convalescent
      sera, and very high values were still detectable 10 to 20 years postinfection.
      IgG ELISA is therefore useful for the testing of immunity and in
      seroepidemiological studies. Acute and convalescent sera from HFRS patients in
      Korea and the Asian USSR showed no or only very weak reactivity in the Puumala
      virus IgG and IgM ELISA. These results are consistent with the "one-way" crossing
      described earlier.

PMID- 1982372
TI  - Antigenic variations in West Nile virus strains isolated in Madagascar since
      1978.
AB  - The antigenic interrelationship between 52 Madagascan West Nile isolates and two
      prototype viruses (Eg101 and G2266) was assessed by an immunofluorescent
      technique using monoclonal antibodies. This analysis enabled us to define 5
      groups of variants, 4 of which were closer to the Egyptian strain (Eg101) than to
      the Indian prototype (G2266). Groups II and V were dominant whereas strains of
      groups I and IV were less numerous. One strain belonging to group III was
      antigenically similar to the Indian strain. Antigenic variations were observed
      among viruses isolated from man, birds and different mosquito genera. Geographic
      variations were also observed. Exchanges exist between Madagascar and the African
      continent by means of migratory birds which seem to be instrumental in
      disseminating the virus and introducing the antigenic variants.

PMID- 1982373
TI  - [Detection of a carrier of hemophilia B by restriction polymorphism using a non
      radioactive hybridization technique].

PMID- 1982375
TI  - Toxic exudate from the hard coral Goniopora tenuidens.
AB  - Ten colonies of Goniopora tenuidens were placed individually in sea water for 1
      hr after which time the sea water was assayed using toxicity to another hard
      coral Galaxea fascicularis and to other colonies of G. tenuidens. Sea water from
      eight of the 10 colonies assayed was toxic to at least one of the bioassay
      organisms. Thus, G. tenuidens can extrude biologically active substances that
      adversely affect potential competitors, both interspecific and conspecific.

PMID- 1982374
TI  - Modification of carboxyl groups in sea anemone toxin RTX-III from Radianthus
      macrodactylus.
AB  - The toxin was treated with [14C]trimethyloxonium tetrafluoroborate or [3H]glycine
      methyl ester in the presence of 1-ethyl-3(3-dimethylaminopropyl) carbodiimide.
      Esterification of separate carboxyl groups with [14C]trimethyloxonium
      tetrafluoroborate decreased the toxicity no more than two-fold. Blocking of any
      single carboxyl group with [3H]glycine methyl ester did not cause more than a two
      fold decrease of toxicity, and modification of two carboxyl groups caused no more
      than a six-fold decrease. Partial localization of modified residues in the amino
      acid sequence was performed. By circular dichroism, it was shown that the
      decrease of toxicity was not associated with alteration of secondary or tertiary
      structure. It is concluded that free carboxyl groups are not absolutely essential
      for toxicity, however they are necessary for expression of the maximum RTX-III
      toxicity.

PMID- 1982376
TI  - Imprinting a determined state into the chromatin of Drosophila.
AB  - The Polycomb gene of Drosophila melanogaster is a member of a class of genes
      involved in the clonal transmission of the repressed state of bomeotic regulatory
      genes through development. Genetic evidence, and the finding of a molecular
      similarity between the Polycomb protein and a heterochromatin-associated protein
      of Drosophila, suggest that this mechanism of repression might be imprinted in
      the structure of the chromatin, rather than being sustained through the action of
      diffusible regulatory factors.

PMID- 1982377
TI  - [Features of the interconversion of alpha-ketoglutarate--glutamate in brain
      mitochondria of exothermic animals during hibernation].
AB  - It has been found that there exists a correlation in the dynamics of changes in
      the amount of glutamate, alpha-ketoglutarate, glutamine, ammonia and activity
      level or alpha-ketoglutarate dehydrogenase, NADP-glutamate dehydrogenase,
      glutamine synthetase and glutaminase in the brain of young carp in the process of
      winter starvation. It has been stated that under condition of energy deficiency
      and meaningful amount of ammonia in the organism of hibernating fish, its binding
      parallel with the known glutamine synthetase mechanism may proceed in the course
      of the NADP-glutamate dehydrogenase reaction which balance is shifted towards the
      glutamate synthesis. This reaction is supposed to provide the outflow of alpha
      ketoglutarate from the citric cycle, which intensifies energy deficiency of the
      organism.

PMID- 1982378
TI  - [Changes in the content of glutamic, aspartic and gamma-aminobutyric acids in
      mitochondrial fractions of limbic system structures of the dog brain during
      postnatal ontogenesis].
AB  - Calculation of the amount of mitochondria isolated from 1 g of fresh tissue has
      shown that the amount of glutaminic (GA), aspartic (AsA) and gamma-aminobutyric
      (GABA) acids in the initial mitochondrial fraction of the limbic structure
      increased during the postnatal ontogenesis and reached the "adult" level in dogs
      aged 1 year. The GA amount in all the studied periods of the ontogenesis exceeded
      the AsA and GABA levels in the mitochondrial fraction of the limbic structure.

PMID- 1982379
TI  - [52d Cologne Dermatology Meeting of the Cologne University Dermatology Clinic 24
      January 1990].
AB  - Patients with the following diagnoses were presented: pyoderma gangraenosum in a
      patient with myelodysplastic syndrome passing into an acute myelomonocytic
      leukemia and specific cutaneous infiltration, primary genital infection with
      herpes simplex virus, type 1 (HSV-1) in an adult patient, pellagroid, Sweet's
      syndrome with follicular involvement, Sweet's syndrome in a patient with cancer
      of the breast, lichen amyloidosus, angiolymphoid hyperplasia with eosinophilia,
      Darier's disease 1. associated with basal cell carcinoma 2. with specific
      cutaneous infiltrations in a patient with acute myeloid leukemia, body building,
      anabolic steroids and fertility, multiple trichodiscomas and perifollicular
      fibromas, Buschke's scleroedema adultorum, extensive necrobiosis lipoidica
      without diabetes mellitus, extramammary, multifocal type of Paget's disease.

PMID- 1982380
TI  - [Report on the 14th annual congress of the German Society of Lymphology in
      Gottingen].

PMID- 1982381
TI  - [Measuring psychophysiologic variables during conversations. Quantifying pulse
      volume changes].
AB  - Little is known about connections between events in verbal communication and
      related physiological variables. Usually used procedures in quantification of
      pulsevolume data are based on simplifications neglecting essential
      characteristics of the curve between heart beats. It is shown that the concept of
      interbeat-intervals (IBI) underlying conventional methods hides these
      characteristics putting up with a delay in time between heart beats and related
      verbal factors. An alternative procedure of the extraction of period and
      amplitude is demonstrated. A software-package is developed to transform and
      interactively control the analysis of the pulsevolumesignal (filtering and vector
      transformation). As results quasi-continuous time series of period and amplitude
      of the pulsecurve are shown, tracing the shape of the curve in each cardiac
      cycle. Some first applications of the method in stress research are discussed.
      The method is appropriate especially for detecting "short time" changes of
      cardiac activity in naturalistic observational settings (e.g. dyadic
      interaction).

PMID- 1982382
TI  - [Activating effect of various kinds of semantic knowledge].
AB  - The question if preactivation effects are to be observed during the within
      conceptual storage of knowledge, when the prime is a general term or a peripheral
      term, was tested with the aid of the priming instrument. The primary effect
      appears only for the peripheral term-relation when the prime is presented for an
      interval of 1000 ms. During the between-conceptual storage, the central meaning
      of the predicate for active knowledge could not be confirmed. The predicate as
      prime led to no significant preactivation when a matched object-case was
      presented.

PMID- 1982383
TI  - [State-dependent processing of serial signals].
AB  - The relation between EEG patterns and performance, which was found
      experimentally, gives evidence for a state dependent information processing. The
      power distribution of the EEG one second before the stimulus onset determines the
      state measured by the used data acquisition system. To solve the on-line
      identification of the state four different approaches are proposed and compared.
      The two modes of triggering the stimulus onset labeled by alpha wave state and
      non alpha wave state led to significantly different reaction times. The proposed
      stochastic recurrence equation can be used to model the scanning process
      performed by 17 subjects in solving the task of searching the first number in a
      string of characters. The model is based on the decomposition of the measured
      reaction times according to the assumed elementary processes.

PMID- 1982384
TI  - The NCES reconsidered: summary of a 1989 workshop. National Childhood
      Encephalopathy Study.
AB  - A 1989 workshop provided a forum for independent review of the National Childhood
      Encephalopathy Study (NCES). No official summary will be published. Workshop
      panelists noted: firstly, that the magnitude of the reported association between
      acute neurological illness and pertussis vaccine might have been overestimated
      because of bias, but bias was believed unlikely to account for all of the excess
      risk; and secondly that because of problems with study design and methodology,
      the NCES is not informative with regard to long-term outcome of acute
      neurological illness associated with recent diphtheria-tetanus-pertussis (DTP)
      vaccination. The workshop panel discouraged use of the NCES estimate of the
      attributable risk of persistent neurological damage.

PMID- 1982385
TI  - Energy donor-dependent effect of Cd2+ on [14C]glutamate transport in
      Staphylococcus aureus.
AB  - In starved cells of Cd2(+)-sensitive Staphylococcus aureus 17810S preloaded with
      either glutamate or pyruvate, [14C]glutamate transport was blocked by 10 microM
      Cd2+, whereas in cells preloaded with lactate, [14C]glutamate transport was not
      affected. This differential effect of Cd2+ could be due to the presence or
      absence of dithiols in the substrate oxidizing systems. In starved cells of
      Cd2(+)-resistant strain 17810R preloaded with either of the three substrates,
      [14C]glutamate transport was insensitive to 10 microM Cd2+.

PMID- 1982387
TI  - Hearing in the aged. The European Concerted Action Project. Proceedings of a
      workshop held in Helsingor, Denmark. November 26-29, 1989.

PMID- 1982386
TI  - Plasma concentrations of glucagon during hyperglycemic clamp with or without
      somatostatin infusion in obese subjects.
AB  - The aim of the present study was to evaluate whether the inhibitory effect on
      pancreatic A-cell exerted by hyperglycemic hyperinsulinemia and/or by
      somatostatin administration is impaired in human obesity. For this purpose plasma
      glucagon concentrations were measured in 8 obese and 8 nonobese nondiabetic
      subjects during a 4-h hyperglycemic clamp. Synthetic cyclic somatostatin-14 was
      infused at the rate of 2.5 nmol/min during the third hour of the study. Fasting
      plasma glucagon was higher in obese than in nonobese subjects (242 +/- 32 vs 163
      +/- 15 pg/ml, p less than 0.05) (mean +/- SEM). In the last 20 min of the glucose
      infusion period preceding somatostatin administration (100-120 min of the study)
      plasma glucagon averaged 195 +/- 26 pg/ml in obese and 122 +/- 13 pg/ml in
      nonobese subjects (p less than 0.05), with a reduction of 19 +/- 3% in the former
      and 28 +/- 4% in the latter (p = n.s.). In both groups somatostatin infusion did
      not result in a further decrease in plasma glucagon, which averaged 192 +/- 27
      pg/ml in obese and 123 +/- 16 pg/ml in nonobese subjects (p less than 0.05) in
      the 160-180 min period of the study. Also after discontinuing somatostatin
      infusion plasma glucagon levels did not change. These results suggest that in
      human obesity hyperglycemic hyperinsulinemia has a normal inhibitory effect on
      pancreatic A-cell and that somatostatin administration has no additive effect on
      hyperglycemia and hyperinsulinemia in either obese or nonobese nondiabetic
      subjects.

PMID- 1982388
TI  - General histopathological changes in the central nervous system with age.

PMID- 1982389
TI  - Glutamate neurotoxicity in the cochlea: a possible consequence of ischaemic or
      anoxic conditions occurring in ageing.
AB  - Glutamate is considered to be one of the most common neurotransmitters in the
      fast excitatory synapses in the central nervous system. On the other hand, its
      excitotoxic properties are increasingly cited to explain some of the brain damage
      linked with hypoxia and ischaemia: i.e., those that occur frequently in ageing.
      An excess release of glutamate could, either directly or indirectly, activate
      receptors on the postsynaptic neuron, causing ion influxes accompanied by a
      massive entry of water, which would lead to an acute swelling of dendrites. In
      addition, calcium influx deregulates calcium homeostasis, which could lead to
      cell death. In the cochlea, glutamate is now considered to be one of the best
      candidates to mediate neurotransmission between inner hair cells (IHCs) and the
      auditory nerve dendrites. Among the variety of anatomical and physiological
      findings supporting the glutamate hypothesis, is the striking similarity of acute
      damage in the organ of Corti caused by exposure to a glutamate analogue (kainic
      acid), or by hypoxia, or even by an intense loud noise. In all cases an immediate
      swelling is observed, specifically affecting the radial afferents below the IHCs.
      The best explanation for this swelling is related to glutamate (or glutamate
      analogue) excitotoxicity. Thus, some of the cochlear damage that occur with
      ageing, especially the loss of the radial afferent fibres and type I ganglion
      cells, might well be attributed to glutamate excitotoxicity linked to vascular
      atrophy. The present paper discusses this hypothesis.

PMID- 1982390
TI  - [Chromatographic purity tests of various phenothiazine derivatives. I. Thin-layer
      chromatography].
AB  - Chromatographic purity tests of four phenothiazine derivatives chlorpromazine,
      levomepromazine, promethazine and trifluoperazine have been developed. The
      adsorptive and partition methods are suitable to the separation of the above
      substances and intermediates as well as side products of their productions. The
      most common impurities of final products were detected by qualitative purity
      tests. Densitometric quantitative determinations were carried out on silicagel
      layer using the solvent system cyclohexanebenzene-diethylamine. Quantity of
      intermediate impurities were 0.15-0.96%.

PMID- 1982391
TI  - [Chromatographic purity tests of various phenothiazine derivatives. II. Gas
      chromatography].
AB  - Gas chromatographic purity tests of four phenothiazine derivatives
      chloropromazine, levomepromazine, promethazine and trifluoperazine have been
      described. Chromatographic system has been optimized that is suitable to the
      separation of the above substances and their intermediates as well as their side
      products. Thermostabilities of phenothiazine derivatives were determined, their
      thermal decompositions were investigated under gas chromatographic circumstances
      and the data obtained were completed with data of their thermoanalytical tests.
      Optimal conditions have been worked out and by applying them thermal
      decomposition of compounds could be minimized. Authors have drawn attention to
      formation of artificial products which could not be avoided therefore taking into
      account requirements of purity tests the application of the method is
      problematical.

PMID- 1982392
TI  - [Effect of Chinoin-103 on K(+)-activated pNPPase in the rat heart].
AB  - Effect of a new beta receptor blocking agent, an aryl oxybutanolamine derivative,
      the Chinoin--103 on K(+)-activated pNPP-ase activity has been studied.
      Propranolol and practolol were used as reference substances. It has been
      established that Chinoin-103 in concentration of 10(-4) M significantly hindered
      total pNPP-ase activity. On the other hand base pNPP-ase activity did not
      significantly change on the effect of the highest investigable concentration.
      Study of enzyme kinetic parameters has shown that decrease of base pNPP-ase
      activity can be attributed to decrease of reaction rate (Vmax decreases) at the
      same time enzyme affinity to pNPP substrate significantly increases (Km
      decreases). Taking into consideration the structural similarity of propranolol
      and Chinoin--103 it is presumable that Chinoin--103 can interact with components
      of membrane like propanolol and impediment of pNPP-ase activity can be attributed
      to the interaction.

PMID- 1982393
TI  - Effects of four dopamine agonists on l-tetrahydropalmatine-induced analgesia and
      electroacupuncture analgesia in rabbits.
AB  - The effects of icv 4 dopamine (DA) agonists on analgesia caused by iv l
      tetrahydropalmatine (THP) 8 mg/kg or by electro-acupuncture (EA) were studied by
      using the potassium iontophoretic dolorimetry in rabbits. The results showed that
      both THP-induced analgesia and EA analgesia were markedly attenuated by icv of DA
      or apomorphine (Apo), 2 mixed D1/D2 agonists. Similar results were obtained when
      SKF-38393, a selective D1 agonist, was applied. On the contrary, quinpirole
      hydrochloride (Qui), a selective D2 agonist, was found to enhance the analgesic
      action of THP or EA. However, DA, Apo, SKF-38393 or Qui per se did not influence
      the baseline pain threshold. All these observations indicate that functional
      alterations in DA receptor activities may be involved in THP-induced analgesia
      and EA analgesia, in which D1 and D2 subtype receptors exert different roles.

PMID- 1982395
TI  - Consensus on hyperthermia for the 1990s. Clinical practice in cancer treatment.
      XII International Symposium on Clinical Hyperthermia. Rome, April 27-29, 1989.

PMID- 1982394
TI  - [Effects of ranitidine and cimetidine on automaticity in isolated myocardium of
      guinea pig].
AB  - At 0.1-30 mumols/L, neither ranitidine (Ran) nor cimetidine (Cim) inhibited the
      rate of spontaneous contraction in isolated right atria of guinea pig. When the
      concentration was higher than 100 mumols/L, both Ran and Cim exhibited weak
      negative chronotropic effects with IC50 of 109 +/- 3 and 436.5 +/- 1.9 mumols/L,
      respectively. However, the positive chronotropic effects of histamine (H) were
      markedly antagonized by Ran and Cim with IC50 of 0.40 +/- 0.29 and 1.8 +/- 0.6
      mumols/L respectively. Ran (0.1 mumols/L) and Cim (1 mumols/L) competitively
      antagonized the concentration-dependent response of positive chronotropic effect
      mediated by H and had no influence on that induced by isoproterenol in right
      atria of guinea pig. Ran (10 mumols/L) and Cim (50 mumols/L) prevented the
      abnormal automaticity elicited by H and H (0.12 +/- 0.09 mumols/L) + Oua (0.04 +/
      0.02 mumols/L) which acted synergically. The abnormal automaticity induced by
      Oua (1.5 +/- 2.3 mumols/L) was antagonized by Ran (10 mumols/L) and not by Cim
      (50 mumols/L). Our results suggest that these effects of Ran and Cim are mainly
      attributed to cardiac H2 receptor blockade.

PMID- 1982396
TI  - New directions in understanding dementia and alzheimer's disease. Proceedings of
      a conference. May 25-26, 1989, Plattsburgh, NY.

PMID- 1982397
TI  - Fetal alcohol exposure: cellular toxicity and molecular events involved in
      toxicity.

PMID- 1982398
TI  - Alcohol induction of ferritin expression in a human hepatoblastoma cell line (HEP
      G2).
AB  - Hyperferritinemia, an unclear mechanism, is frequently observed in chronic
      alcoholics. The aim of this work was to study the effect of alcohol on ferritin
      expression in a human hepatoblastoma cell line, HepG2. This cell line proved to
      be sensitive to alcohol, since alcohol increased gamma-GT activity both in cells
      and media. The most striking result was the increase of ferritin in cells and
      media by alcohol. Moreover, this effect was specific, since it contrasted with a
      decrease in total protein synthesis and secretion, a decrease in transferrin
      excretion and a lack of effect on orosomucoid. In our model, alcohol was able to
      induce, in a specific manner, ferritin expression.

PMID- 1982399
TI  - Human gastric alcohol dehydrogenase: its inhibition by H2-receptor antagonists,
      and its effect on the bioavailability of ethanol.
AB  - Two types of alcohol dehydrogenase isoenzymes (differing in their affinity for
      ethanol, sensitivity to 4-methylpyrazole, and electrophoretic migration) have
      been identified in the human stomach. At the high ethanol concentrations
      prevailing in the gastric lumen during alcohol consumption, the sum of their
      activities could account for significant oxidation of ethanol. In vitro, these
      activities were inhibited by cimetidine and ranitidine, but not by famotidine. In
      vivo, therapeutic doses of cimetidine (but not of famotidine) increased blood
      ethanol levels when ethanol was given orally, but not when it was given
      intravenously, indicating a significant contribution of the gastric ADH to the
      bioavailability and thereby the potential toxicity of ethanol.

PMID- 1982400
TI  - [Modification of gastrin and somatostatin cells in the gastric antrum in
      experimental diabetes].

PMID- 1982401
TI  - Genetics of response to slow virus (prion) infection.

PMID- 1982402
TI  - Antimicrobial interference with bacterial mechanisms of pathogenicity: effect of
      sub-MIC azithromycin on gonococcal piliation and attachment to human epithelial
      cells.
AB  - The effects of subinhibitory concentrations of azithromycin (CP-62,993) on the
      piliation and attachment properties of Neisseria gonorrhoeae were examined.
      Subinhibitory concentrations of azithromycin significantly reduced the percentage
      of gonococci that expressed assembled pili on their surfaces by decreasing pilin
      subunit synthesis and substantially decreased gonococcal adherence to human
      mucosal cells.

PMID- 1982403
TI  - Application of molecular science to caries and periodontal disease. 4th European
      Symposium of Borderland Between Caries and Periodontal Disease. Geneva,
      Switzerland, 25-26 January 1990.

PMID- 1982404
TI  - Carbohydrates as recognition molecules for bacterial adhesins: methodology and
      characteristics.
AB  - Future attempts at developing inhibitors of dental plaque formation necessitate
      characterization of the bacterial-host, as well as the inter-bacterial
      recognition processes. Bacterial binding to a panel of solid-phase reference
      glycolipids was used to reveal the recognition of internal receptor sequences,
      low-affinity cooperative interactions, and adhesin variants with slightly shifted
      receptor epitopes. This epitopic variation may be a mechanism for shifting the
      host and tissue tropism of the bacteria, and may have evolved in response to the
      topography and expression of receptor epitopes at the host tissue surfaces.

PMID- 1982405
TI  - Sequencing and characterization of the 185 kDa cell surface antigen of
      Streptococcus mutans.
AB  - The gene spa P (formerly designated as spa P1) encoding the Mr 185,000 surface
      antigen I/II of Streptococcus mutans, serotype c (strain NG5) has been sequenced.
      The deduced amino acid sequence of antigen I/II (1561 residues) includes a
      putative signal peptide (residues 1-38), as well as a transmembrane region
      (residues 1537-1556). The N-terminal part of the protein (residues 39-550) is
      particularly rich in alanine and includes three tandem repeats of a sequence of
      82 residues. This region is predicted to be alpha-helical, adopting a coiled-coil
      formation, and may account for the cell surface hydrophobicity associated with
      expression of antigen I/II. In contrast the C-terminal region (residues 800-1549)
      is proline-rich, favouring an extended conformation. Comparison with the sequence
      determined from Strep. mutans strain MT8148 showed that antigen I/II is highly
      conserved with the exception of a short central region (residues 750-805). N
      terminal sequencing of purified antigens I and II components indicated that
      antigen I extends from the amino-terminus of the intact Mr 185,000 surface
      antigen while antigen II extends from residue 996.

PMID- 1982407
TI  - In vivo body composition studies. Proceedings of an international symposium. June
      20-23, 1989, Toronto, Ontario, Canada.

PMID- 1982406
TI  - Genetic approach to the study of epidemiology and pathogenesis of Actinobacillus
      actinomycetemcomitans in localized juvenile periodontitis.
AB  - Actinobacillus actinomycetemcomitans isolates from periodontal pockets were
      examined for restriction fragment-length polymorphism using a characterized 4.7
      kb DNA probe. A total of 6 patterns of RFLP was found in 133 isolates originating
      from 12 subjects. No relatedness was found between RFLP types and serotypes.
      Different periodontal sites within the same subject and different individuals
      within the same family sometimes showed only one type of A. actinomycetemcomitans
      RFLP. When members among the same family showed 2 RFLP types, children were
      always infected with the A. actinomycetemcomitans strains found in at least one
      of the parents. These findings support the concept of familial spread of A.
      actinomycetemcomitans. A. actinomycetemcomitans RFLP type B, corresponding to
      reference strain JP2, seems to be particularly virulent, as indicated from the
      presence of RFLP type B in 3 subjects who converted from a healthy periodontal
      state to localized juvenile periodontitis. RFLP type B was not detected in any of
      the 21 A. actinomycetemcomitans-infected patients with adult periodontitis. The
      RFLP method seems to be useful in determining the epidemiology and possibly the
      potential virulence of periodontal strains of A. actinomycetemcomitans.

PMID- 1982408
TI  - Ethanol-induced inhibition of testosterone biosynthesis in rat Leydig cells: role
      of mitochondrial substrate shuttles and citrate.
AB  - The mechanisms by which ethanol inhibits testicular testosterone synthesis in
      rats were studied in vitro using isolated rat Leydig cells. The ethanol-induced
      inhibition was reversed by 4-methylpyrazole, an alcohol dehydrogenase inhibitor,
      suggesting that ethanol metabolism was responsible for this inhibition. L
      glutamate and pyruvate, when added to the Krebs-Ringer incubation medium,
      reversed the inhibition by ethanol. The membrane glutamate receptor agonists
      kainic acid and quisqualic acid had no effects, indicating metabolic mechanisms
      for the L-glutamate action. This was verified also by observations that the
      metabolic transaminase inhibitors aminooxyacetate and cycloserine inhibited
      testosterone synthesis. In the amino acid supplemented Krebs-Ringer, pyruvate
      could not fully prevent inhibition by ethanol alone, but addition of L-glutamate
      to this medium abolished ethanol-induced inhibition. Experiments performed using
      a new inhibitor of testosterone biosynthesis in intact Leydig cells,
      triethylcitrate, indicated that active citrate metabolism, and/or efflux from
      mitochondria, was essential for the steroidogenic pathway from pregnenolone to
      testosterone in the smooth endoplasmic reticulum. The early steps of hCG
      stimulation before pregnenolone formation were most sensitive to its effect. Our
      results indicate that the inhibition of steroidogenesis by ethanol results from
      decreased availability of the metabolites involved in the substrate shuttles
      maintaining the NAD(P)H redox states between the mitochondrial and the smooth
      endoplasmic reticulum compartments, and that the inhibition can be overcome by a
      proper selection of exogenous sources for these metabolites.

PMID- 1982409
TI  - Circulating immune complexes in systemic necrotizing vasculitis of the
      polyarteritis nodosa group. Comparison of HBV-related polyarteritis nodosa and
      Churg Strauss Angiitis.
AB  - Levels of immune complexes (IC) were measured before treatment in 16 patients
      affected with classic polyarteritis nodosa (PN) or Churg Strauss Angiitis (CSA).
      The six patients with PN were positive for HBV markers. The others presented
      severe asthma. IgG containing immune complexes were measured using Raji cell
      assay. Normal level was 4,642 +/- 509 (mean +/- SEM). IC levels were
      significantly different in patients with and without HBV markers. When HBV was
      present, mean IC level was 7,185 +/- 2,472. In the absence of HBV markers, mean
      IC level was 26,462 +/- 10,796. These results confirm that systemic vasculitis is
      an heterogeneous group of diseases and further suggest that pathogenesis of
      vasculitis is different in patients with asthma and those with HBV markers.

PMID- 1982410
TI  - Lymphocyte population changes in cats naturally infected with feline
      immunodeficiency virus.
AB  - Feline immunodeficiency virus (FIV) is associated with feline acquired
      immunodeficiency syndrome (FAIDS) and has been suggested as a model for HIV
      induced human AIDS. The most obvious immunological defect in HIV infection is a
      reduction in CD4+ cell numbers and an inversion of the CD4:CD8 ratio. To
      determine whether the same is true in FIV infection, we analyzed by flow
      cytometry using a panel of monoclonal antibodies to feline lymphocyte populations
      the CD4:CD8 ratios in cats naturally infected with the virus. We report that 13
      of 19 FIV-infected cats had ratios below the 5th percentile of normal cats (0.57,
      established from analysis of 39 normal cats) and 18 of 19 had ratios below 1.
      Repeated analyses over a period of several months revealed the inverted ratios to
      be consistent. Analysis of lymphocyte numbers in FIV-infected cats shows that the
      inverted ratios are due to a decrease in CD4+ T cells, while CD8+ T and B cells
      remain relatively normal in number. Analysis of a group of cats with a variety of
      other chronic diseases, including feline leukemia virus (FeLV) infections,
      revealed a near-normal distribution of CD4:CD8 ratios. These findings are similar
      to those in HIV infections and indicate that, like HIV, FIV causes a selective
      reduction in CD4+ cells and should be an excellent model for studying retrovirus
      induced AIDS.

PMID- 1982411
TI  - Immunodeficiency in HIV-2 infection: a community study from Guinea-Bissau.
AB  - In a community study in Guinea-Bissau, West Africa, 47 HIV-2-seropositive cases
      and 87 matched controls were evaluated immunologically using immuno-alkaline
      phosphatase linked to avidin-biotin complex for the assessment of CD4 and CD8
      status. HIV-2-seropositive individuals had significantly lower total numbers of
      CD4 cells and CD4/CD8 ratios, 38% having a total number of CD4 cells less than or
      equal to 0.5 x 10(9)/l and 36% having a CD4/CD8 ratio less than or equal to 0.8.
      Total numbers of CD4 cells less than or equal to 0.5 x 10(9)/l or CD4/CD8 ratio
      less than or equal to 0.8 were found in 53% of the HIV-2 seropositives compared
      with 11% among controls [odds ratio (OR) = 7.3; 95% confidence interval (CI): 3.1
      17.1]. Lymphadenopathy was significantly more frequent among HIV-2 seropositives
      than among controls (OR = 3.4; 95% Cl: 1.5-7.6). HIV-2 seropositives with
      lymphadenopathy had significantly fewer lymphocytes (P = 0.008) and lower total
      CD4 (P = 0.029) and total CD8 number (P = 0.011) than HIV-2 seropositives without
      lymphadenopathy. This study indicates that HIV-2 has a significant
      immunosuppressive effect.

PMID- 1982412
TI  - Sequential autonomic function tests in HIV infection.
AB  - Cardiovascular autonomic function tests were carried out on 22 men at varying
      stages of HIV infection. Thirteen were asymptomatic, seven had persistent
      generalized lymphadenopathy, and two had Kaposi's sarcoma. Pupil cycle times were
      also measured. Except for one subject with definite autonomic abnormalities, all
      the rest had almost normal test results. There were no correlations between
      individual tests of immune function and the autonomic test results. The tests
      were repeated 9-18 months later in 12 men, four of whom were taking zidovudine at
      that time. Although there was evidence of progression of HIV-associated immune
      dysfunction, there was no significant deterioration in autonomic function. In the
      single patient with abnormal autonomic function, these changes appeared to
      reverse on treatment with zidovudine.

PMID- 1982413
TI  - A fluoroquinolone (DR-3355) protects human lymphocyte cell lines from HIV-1
      induced cytotoxicity.
AB  - HIV-1 infection of human CD4+ lymphocyte cell lines results in cell death.
      Treatment, but not pretreatment, of infected cells, with a fluoroquinolone
      antibiotic, DR-3355, protects a significant subfraction of cells from HIV-1
      mediated cytolysis. All surviving cells have lost expression of the CD4 antigen,
      but do (MT-4) or do not (CEM) express viral antigens and produce infective virus.
      The rescued CEM and MT-4 cells are phenotypically stable and do not require
      continuous exposure to the drug for survival.

PMID- 1982414
TI  - HIV-2 in Los Angeles.

PMID- 1982415
TI  - Three-dimensional reconstruction of the sevenfolded form of Bacillus subtilis Gro
      EL Chaperonin.
AB  - Bacillus subtilis grown at 42 degrees C produces a major form of Gro EL-like
      chaperonin that has been analyzed by electron microscopy. Most of the views show
      a clear sevenfold symmetry when studied by rotational analysis. The particles
      were classified into defined families by multivariate analysis and supervised
      fuzzy-set classification methods, and those belonging to a sevenfold family were
      averaged to produce a two-dimensional representative projection. These selected
      particles were then used, when titled by 55 degrees in the microscope goniometer
      stage, as the starting projections for a three-dimensional reconstruction
      protocol based on the random conical tilt series method. The resulting
      reconstruction shows the Gro EL-like chaperonin from B. subtilis as a cylindrical
      body with seven well defined lobules arranged almost parallel to the longitudinal
      axis of the particle. There is a channel that is placed along this axis and
      appears fully open in both sides. The geometry of the channel is polar and
      presents differences in both faces of the particle.

PMID- 1982416
TI  - Ontogeny of renal beta adrenoceptors in the sheep.
AB  - The renal vasodilatory response to beta-2 adrenoceptor stimulation is greater in
      fetal than adult sheep. Since this phenomenon could not be explained by
      differences in cAMP-mediated events, we examined the ontogeny of renal beta
      adrenoceptor subtypes by radioligand binding using the beta adrenergic antagonist
      125I-pindolol. The specific binding of 125I-pindolol was saturable, reversible,
      and stereoselective. Competition studies using the selective beta-1 and beta-2
      adrenergic antagonists (ICI 89406 and ICI 118551, respectively) revealed two beta
      adrenoceptor subtypes in adult kidneys but only the beta-2 subtype in fetal
      kidneys. Preincubation of renal cortical membranes with either the beta-1 or the
      beta-2 adrenergic antagonist prior to competition studies in adult kidneys
      decreased specific binding and resulted in the detection of only one beta
      adrenoceptor subtype. Preincubation of fetal kidneys with the beta-1 adrenergic
      antagonist did not affect binding characteristics; preincubation of fetal kidneys
      with the beta-2 adrenergic antagonist markedly decreased specific binding from 64
      +/- 2% (n = 4) to 29 +/- 2% (n = 3) (P less than 0.05). Analysis of Rosenthal
      plots revealed similar beta adrenoceptor densities and affinities between fetal
      and adult kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1982418
TI  - Functional and phenotypic delineation of two subsets of CD4 single positive cells
      in the thymus.
AB  - CD4 single positive thymocytes are the fraction of mature thymocytes that
      contains precursors of MHC class II restricted T cells. In the experiments
      presented here, we demonstrate phenotypic and functional heterogeneity amongst
      CD4 single positive thymocytes from adult mice. Approximately 70% of these cells
      adhere to anti-CD8 antibody-coated dishes and therefore express low levels of CD8
      molecules. They are referred to here as CD8loCD4hi. The remaining 30% are CD8
      CD4hi. The CD8loCD4hi subset also expresses 3-fold higher surface levels of heat
      stable antigen (HSA) than CD8-CD4hi thymocytes. Both CD4hi subsets express high
      levels of the alpha beta TCR/CD3 complex on the cell surface, and can proliferate
      in response to allogeneic cells expressing MHC class II differences but not to
      cells expressing only class I disparate molecules. However, CD8-CD4hi thymocytes
      are self-sufficient in such a proliferative response, whereas CD8loCD4hi
      thymocytes require exogenous IL-2 for optimal proliferation. The results suggest
      that CD8loCD4hi thymocytes are not completely mature. Their phenotype suggests
      that they might be descendants from CD8hiCD4hi double positive thymocytes, and
      that they have begun to down-regulate gradually CD8 and HSA molecules. The
      relationship between the two CD4hi single positive subsets is discussed.

PMID- 1982419
TI  - The embryonic position. The Molecular Biology of Vertebrate Development sponsored
      by the European Molecular Biology Organization, Heidelberg, Germany, September 17
      20, 1990.

PMID- 1982417
TI  - Molecular biology of adrenergic and dopamine receptors and the study of
      developmental nephrology.
AB  - Neurotransmitters convey specific messages by binding to receptors on the cell
      membrane surface. Receptors are linked to membrane-bound, signal-transducing
      proteins which act as intermediaries in the generation of second messengers that
      elicit biological responses. Cell surface receptors could be grouped into
      families that utilize common systems for their signal transmission. These classes
      include the growth factor receptors, the transporter receptors which internalize
      their ligands, ion channels, and G-protein-coupled receptors. In the past few
      years, the cDNAs and/or genes of a number of G-protein-coupled receptors have
      been cloned. Structural analysis of the G-protein-coupled receptors, as well as
      the other classes of receptor, shows that those receptors which use a common
      signaling pathway have similar topographies and share significant sequence
      homology. Adrenergic and dopamine receptors are examples of receptors coupled to
      G proteins. This review outlines some strategies in the study of adrenergic and
      dopamine receptors using molecular biology techniques and how they relate to
      investigations in developmental nephrology.

PMID- 1982420
TI  - The guanylyl cyclase receptor family.
AB  - Cyclic GMP (cGMP) signals through protein kinases, ion channels, and possibly
      other effector systems as a second messenger. Its synthesis is regulated by
      guanylyl cyclase, whose activity is found in various cellular compartments
      including the plasma membrane and cytosol. A soluble form of guanylyl cyclase,
      which occurs as a heterodimer, appears to serve as a receptor for nitric oxide or
      nitrosothiols, or both. Recent research suggests the presence of multiple
      subtypes of the soluble form of guanylyl cyclase and tissue-specific expression
      of the different forms. At least two different forms of the plasma membrane
      guanylyl cyclase are known to occur in various mammalian tissues. One form, GC-A,
      is a receptor for atrial natriuretic peptide, and the binding of ligand causes
      marked increases in cGMP production. The other form, GC-B, is stimulated more
      effectively by a brain natriuretic peptide than by atrial natriuretic peptide,
      but its natural ligand remains in question. Both plasma membrane forms of the
      enzyme contain a single, putative transmembrane domain. The intracellular region
      of both forms contains a protein kinase-like domain just within the transmembrane
      domain. The protein kinase-like domain is followed by a cyclase catalytic region
      near the carboxyl terminus that is homologous to two internally homologous
      domains found in a bovine brain adenylyl cyclase. The possibility that other
      guanylyl cyclase receptor subtypes exist is now being explored. If they do, we
      may subsequently find that a diversity of specific ligands signals through cGMP.

PMID- 1982421
TI  - Wind me up! Wind me down! Regulation of Eukaryotic DNA Replication, sponsored by
      McGill University, Montreal, Canada, March 5-8, 1990.

PMID- 1982422
TI  - Getting unglued about integrins. The Molecular Basis of Cellular Adhesion: A UCLA
      symposium, sponsored by Genentech and Glaxo Steamboat Springs, CO, USA, January
      20-26, 1990.

PMID- 1982423
TI  - Suppressing times. Negative Controls on Cell Growth: a UCLA symposium, sponsored
      by ICI Pharmaceuticals and Smith Kline and French, Taos, NM, USA, March 3-9,
      1990.

PMID- 1982424
TI  - Turned on by activin. Growth and Differentiation Factors and Development: a UCLA
      symposium, Steamboat Springs, CO, USA, March 31-April 7, 1990.

PMID- 1982425
TI  - Trigeminal intraoral schwannomas.
AB  - This article clinically and histologically details four cases of schwannoma
      presenting in uncommon intraoral locations. The diagnosis and conservative
      management of these benign, encapsulated lesions are discussed. The association
      of intraoral schwannomas with multiple endocrine neoplasia syndrome 111 (MENS
      111) and the need to rule out neurofibromatosis are noted.

PMID- 1982427
TI  - Proceedings of the VIth Complement Genetics Workshop and Conference. July 27-29,
      1989, Mainz, FRG.

PMID- 1982426
TI  - Inhibition of functional properties of tetanus antigen-specific T-cell clones by
      envelope glycoprotein GP120 of human immunodeficiency virus.

PMID- 1982428
TI  - C4 DNA RFLP reference typing report.
AB  - One hundred and three individual DNA samples (including 23 families) were studied
      at the gene level during the reference typing of the fourth component of human
      complement at the VIth Complement Genetics Workshop in Mainz (1989). All samples
      were analyzed with the restriction enzyme Taq I and with two DNA probes
      recognizing the 5' ends of both C4 genes and the two adjacent 21-hydroxylase
      genes. This RFLP is informative for the number of C4 genes as well as for their
      respective gene size. We found a high degree of variation regarding the number of
      C4 genes, i.e. haplotypes with 1-3 structural C4 genes of 16 or 22 kb size. By
      correlating these haplotypes to the complotypes obtained by protein typing for
      C2, BF and C4, it became evident that only minor variation of the C4 gene
      structure within a given complotype is present.

PMID- 1982429
TI  - A new homeobox-containing gene, msh-2, is transiently expressed early during
      mesoderm formation of Drosophila.
AB  - Many homeobox-containing genes of Drosophila regulate pathways of
      differentiation. These proteins probably function as promoter- or enhancer
      selective transcription factors. We have isolated a new homeobox-containing gene,
      msh-2, by means of the polymerase chain reactions (PCR) using redundant primers.
      msh-2 is specifically expressed in mesodermal primordia during a short time
      period early in development. It first appears at blastoderm stage just before the
      ventral invagination of the mesoderm and shortly after twist, a gene required for
      mesoderm formation, is expressed. During germband elongation all the mesodermal
      cells in the segmented part of the embryo express msh-2, but soon afterwards msh
      2 becomes restricted to the dorsal mesoderm, which includes the primordia for the
      visceral musculature and the heart. Prior to muscle differentiation, msh-2
      expression ceases, except for two rows of cells that will be included in the
      dorsal vessel. Embryos that are deficient for the chromosomal region, 93C-F,
      which includes the msh-2 gene, show normal mesoderm invagination and dorsal
      spreading. However, later in development no visceral muscle and dorsal vessel
      differentiation can be detected, but some skeletal muscles do form, albeit
      abnormally. msh-2 expression, except for a patch in the head, is dependent on
      twist function. On the other hand, snail, another mesoderm determinant, does not
      appear to be required for msh-2 initiation, but is necessary for the maintenance
      of msh-2 expression after germband elongation. H2.0, a homeo-box-containing gene
      specifically expressed in visceral mesoderm, is not transcribed in the mesoderm
      in 93C-F deficiency embryos.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1982430
TI  - Development and persistence of catecholaminergic neurons in cultured explants of
      fetal murine vagus nerves and bowel.
AB  - Transient catecholaminergic (TC) cells have been found to appear in the vagal
      pathway and bowel of fetal mice and rats. It has been proposed that these cells
      are migrating vagal crest-derived precursors of enteric neurons that lose their
      catecholaminergic properties when they terminally differentiate. In the current
      experiments, segments of fetal mouse gut were explanted before (day E9) TC cells
      or any neural markers could be detected in situ. Tyrosine hydroxylase (TH)
      immunoreactive neurons developed in vitro in 4/12 such explants; therefore, cells
      with a catecholaminergic potential are present in the gut of at least some
      animals prior to the in situ expression of this phenotype. The neurogenic
      potential of cells in the vagal pathway was similarly tested by studying cultures
      of explanted vagus nerves (day E11). These studies revealed that neural
      precursors were present in the vagi and gave rise in vitro to neurons that
      displayed acetylcholinesterase (AChE) activity and neuron-specific enolase (NSE)
      immunoreactivity. A subset of these neural precursors were capable of migrating
      and formed satellite ganglia at a distance from the explants. Coincident
      expression of NSE and TH immunoreactivities was observed, indicating that at
      least some of the neurons that developed in vitro were derived from TC cells.
      Vagal TC cells, therefore, are neurogenic. Catecholaminergic cells did not
      disappear from cultured explants of vagus nerves or gut provided that these
      tissues contained TC cells at the time of explantation. Instead,
      catecholaminergic neurons developed and persisted in vitro for as long as
      cultures were maintained. These neurons contained aromatic L-amino acid
      decarboxylase as well as TH, NSE and neurofilament immunoreactivities. In
      contrast, if the bowel was explanted after the in situ disappearance of TC cells,
      catecholaminergic cells did not arise in the cultures. These experiments indicate
      that the period of time during which a catecholaminergic phenotype is expressed
      by neural precursors in the fetal vagal pathway and gut is not fixed, but can be
      changed by altering the environment of the cells as occurs when the bowel is
      grown in vitro; moreover, contact with non-neuronal cells within the bowel is not
      by itself sufficient to inactivate catecholaminergic expression. The nature of
      the signal responsible for loss of the catecholaminergic phenotype in situ
      remains to be determined; however, the persistence of catecholaminergic
      expression in vitro should facilitate the investigation of this signal.

PMID- 1982431
TI  - Primary structure and embryonic expression pattern of the mouse Hox-4.3 homeobox
      gene.
AB  - We report the cloning, genomic localization, primary structure and developmental
      expression pattern of the novel mouse Hox-4.3 gene. This gene is located within
      the HOX-4(5) complex, at a position which classifies it as a member of the Hox
      3.1 and -2.4 subfamily, the DNA and predicted protein sequences further confirmed
      this classification. Hox-4.3 has a primary structure characteristic of a Hox gene
      but, in addition, contains several monotonic stretches of amino acids, one of the
      'paired'-like type. As expected from its presence and position within the
      complex. Hox-4.3 is developmentally expressed in structures of either mesodermal
      or neurectodermal origin located or derived from below a precise craniocaudal
      level. However, a very important offset between anteroposterior boundaries within
      neuroectoderm versus mesoderm derivatives is observed. Like other genes of the
      HOX-4(5) complex, Hox-4.3 is expressed in developing limbs and gonads, suggesting
      that 'cluster specificity' could be a feature of the HOX network.

PMID- 1982432
TI  - Isolation of an abdominal-A gene from the locust Schistocerca gregaria and its
      expression during early embryogenesis.
AB  - Using sequence homology to Drosophila homeobox-containing genes, we have cloned a
      homologue of abdominal-A from the locust Schistocerca gregaria. The Schistocerca
      clone encodes a stretch of 78 amino acids including the homeodomain and its
      flanking regions identical to the corresponding region of abdominal-A. We have
      shown by in situ hybridization that this gene is transcribed and have used an
      antibody raised against its protein product to examine the expression of
      abdominal-A during early Schistocerca embryogenesis. Schistocerca is a short germ
      insect. Although the segmented body plan is very similar to that of Drosophila,
      the segments are generated sequentially by a process of growth, not
      simultaneously by subdivision of a syncytial blastoderm. In both organisms,
      abdominal-A is expressed throughout the abdomen from a sharp anterior boundary
      located within the first abdominal segment (A1). The initial activation of the
      genes in the two species differs. Schistocerca initiates expression in a small
      group of cells in the anterior of A2, shortly after this segment is defined by
      the appearance of engrailed protein. This contrasts with the appearance of
      abdominal-A expression in Drosophila, which appears simultaneously throughout the
      entire abdomen.

PMID- 1982433
TI  - Alzheimer's disease and aluminum toxicology.

PMID- 1982435
TI  - Prediction of intrinsic clearance of loxtidine from kinetic studies in rat, dog
      and human hepatocytes.

PMID- 1982436
TI  - Maintenance of differentiated function in cultured rat hepatocytes immortalized
      by transfection with viral DNA.

PMID- 1982437
TI  - Glutamate uptake in sinusoidal membrane vesicles isolated from rat liver: effects
      of streptozotocin diabetes.

PMID- 1982434
TI  - Comparative observations on inorganic and organic lead neurotoxicity.
AB  - Environmental and occupational exposure to lead still generates concern, and
      recent studies have focused such concern on the role of body burden of lead
      during the fetal/neonatal period, especially in the genesis of disturbed central
      nervous system development. This discussion provides some comparative
      observations on the neurotoxicity of inorganic and organic lead species. The
      characteristics acute, predominantly cerebellar encephalopathy associated with
      neonatal high lead exposure contrasts to the subtle, axo-dendritic
      disorganization shown to be associated with low-level neonatal inorganic Pb2+
      exposure. There is a preferential involvement of the hippocampus in both low
      level inorganic Pb2+ and organolead exposure, and the clinical syndromes of
      irritability, hyperactivity, aggression, and seizures are common features of
      disturbed hippocampal function. Neurotransmitter system abnormalities have been
      described with inorganic Pb2+, but recent attention has focused on the
      abnormalities in glutamate, dopamine and/or gamma-aminobutyric acid (GABA)
      uptake, efflux, and metabolism. Abnormalities of GABA and glutamate metabolism
      are also found with the organolead species. While the pathogenesis is still
      unclear, the interactive role of Pb2+ on mitochondrial energy metabolism, Ca2+
      uptake, intracellular Ca2+ homeostasis, and neurotransmitter influx/efflux is
      considered. Consideration is given to low-dose inorganic Pb2+ and organolead
      effects on mitochondrial and/or plasmalemmal membranes inducing either Cl-/OH-
      antiport-linked depolarization, inhibition of intracellular ATP biosynthesis and
      transduction. and/or abnormalities induced due to the preferential affinity of
      Pb2+ for intracellular Ca2(+)-cytoplasmic protein, e.g. calmodulin. Testable
      hypotheses are presented that may provide an understanding of the pathogenesis
      underlying dystrophic neuronal development under the influence of inorganic or
      organolead intoxication.

PMID- 1982438
TI  - The effect of prolactin on acetyl-CoA carboxylase activity in mammary explants
      from pregnant sheep.

PMID- 1982440
TI  - Methods in islet transplantation research. International workshop. Bad Nauheim,
      June 1989.

PMID- 1982439
TI  - Peptides incorporating electrophilic glutamine analogues as potential
      transglutaminase inhibitors.

PMID- 1982441
TI  - Roles of CD4+ and CD8+ cells in islet allo- and xeno-graft rejection.
AB  - We investigated the requirement for and the roles of CD8+ cells and CD4+ cells
      for islet graft rejection in allogeneic and xenogeneic combinations by in vivo
      administration of anti-Lyt2 monoclonal antibody (mAb), anti-L3T4 mAb or both to
      the recipient mice. In BALB/c to B6 (H-2 and non-H-2 incompatible combination),
      administration of anti-Lyt-2.2(CD8) or anti-L3T4(CD4) mAb resulted in rejection
      of most of the grafts, although their survival was prolonged significantly.
      Administration of both mAbs together completely blocked rejection and all
      allografts survived over 100 days with mAb administration. In B10.A(5R) to B10.A
      (H-2K and IA incompatible combination) or B10.AQR to B10.A (H-2K incompatible
      combination), administration of either mAb alone induced indefinite allograft
      survival. In bm12 to B6 (IA incompatible combination), allografts were not
      rejected even in nontreated recipients. In rat-to-mouse combinations,
      administration of anti-L3T4 mAb produced marked prolongation of graft survival
      and 3 out of 8 survived over 100 days. Administration of both mAbs also led to
      prolongation of graft survival which was similar to or better than that of anti
      L3T4 mAb alone. The present results indicated that CD4+ and CD8+ cells
      participate in all types of islet graft rejection studied here and that the
      absolute requirements of CD4+ or CD8+ T cell subsets for islet rejection depend
      on genetic as well as species disparity.

PMID- 1982442
TI  - Structure and regulation of rat liver microsomal stearoyl-CoA desaturase gene.
AB  - The cosmid library of rat genomic DNA was screened with the coding region of
      microsomal stearoyl-CoA desaturase (SCD) cDNA as the probe. Two independent
      clones having 36 kb (SCDI) and 31 kb (SCDII) of inserts were isolated. Southern
      mapping analyses revealed that SCDI codes for SCD and SCDII for an SCD-homologue,
      and that the genes differ markedly in the upstream regulatory regions. Nucleotide
      sequence analysis of SCDI revealed that the SCD gene is organized with 6 exons
      and 5 introns spanning about 15 kb, thus coding an mRNA with an open reading
      frame of 1,074 bp of the desaturase. Transcription starts at 114 by upstream of
      the translation initiation codon, and 32 bp upstream of the transcription
      initiation site there is a TATA box. A sequence similar to Fat Specific Element 2
      (FSE2), the negative regulatory element of adipocyte differentiation, was present
      at 45 bp upstream of the TATA box. The tissue distribution and induction due to
      dietary manipulation of SCDI and SCDII mRNAs as revealed by Northern
      hybridization were markedly different from each other.

PMID- 1982444
TI  - 14th International Symposium on Column Liquid Chromatography. Boston, MA, May 20
      25, 1990. Part I.

PMID- 1982443
TI  - Structure and expression of cDNA for D-amino acid oxidase active against
      cephalosporin C from Fusarium solani.
AB  - D-Amino acid oxidase (DAO) was extracted and purified from cultured mycelia of
      Fusarium solani M-0718 (FERM P-2688). The enzyme was able to oxidatively
      deaminate cephalosporin C to 7-beta-(5-carboxy-5-oxopentanamido)cephalosporanic
      acid. Ninety-eight amino acid residues of the F. solani DAO were determined by
      sequence analysis of 9 peptides derived from Acromobacter protease I digests of
      the protein. Complementary DNAs encoding F. solani DAO were isolated from the F.
      solani cDNA library by hybridization with synthetic oligonucleotide probes
      corresponding to the partial amino acid sequences. Analysis of the nucleotide
      sequences of the clones revealed a 1,186-nucleotide sequence with a 5'-terminal
      untranslated region of 41 nucleotides, an open reading frame of 1,083 nucleotides
      that encoded 361 amino acids, and a 3'-terminal untranslated region of 62
      nucleotides. The amino acid sequence of F. solani DAO had 25% homology to that of
      porcine kidney DAO [EC 1.4.3.3] and 37% homology to that of Trigonopsis
      variabilis DAO. The constructed plasmid overproduced F. solani DAO in Escherichia
      coli. The recombinant DAO had almost the same molecular activity as the native
      DAO against cephalosporin C.

PMID- 1982446
TI  - Ring-substituted analogues of tranylcypromine as monoamine oxidase inhibitors.
AB  - 4-Fluorotranylcypromine and 4-methoxytranylcypromine, in which the 4-position of
      the phenyl ring is protected from metabolic ring hydroxylation, were tested for
      their ability to inhibit, relative to tranylcypromine, monoamine oxidase (MAO) -A
      and -B in rat brain after administration of low doses (1.2 and 3.7 mumol/kg) of
      the drugs. One hour after intraperitoneal injection of the lower dose,
      tranylcypromine was weaker than 4-fluorotranylcypromine and 4
      methoxytranylcypromine at inhibiting MAO-A. After long-term (28 day)
      administration of a dose of 3.7 mumol/kg/day (administered via osmotic
      minipumps), 4-fluorotranylcypromine had a slightly stronger inhibitory effect on
      MAO-B than did the other two drugs. At the same time and dose both 4-substituted
      analogues were slightly more potent inhibitors of MAO-A than was tranylcypromine.
      After 28 days of administration at a daily dose of 1.2 mumol/kg/day, both
      analogues produced greater inhibition of MAO-A and -B than did tranylcypromine. 4
      Methoxytranylcypromine and 4-fluorotranylcypromine were similar in their extent
      of inhibition of MAO-B but the former was more potent than the latter at
      inhibition MAO-A.

PMID- 1982445
TI  - T lymphocytes in the cerebrospinal fluid of patients with multiple sclerosis.

PMID- 1982447
TI  - Recent studies on the MAO inhibitor phenelzine and its possible metabolites.
AB  - Although N2-acetylphenelzine (N2AcPLZ) appears to be only a minor metabolite of
      phenelzine (PLZ), other investigations have demonstrated that it may be worthy of
      study as an antidepressant in its own right. In the present report, the
      possibility of ring hydroxylation as a metabolic route for PLZ was investigated
      in the rat. Indirect evidence for such a route was obtained using iprindole, a
      drug known to block ring hydroxylation. Treatment of rats with iprindole followed
      by PLZ was demonstrated to result in increased brain levels of PLZ and beta
      phenylethylamine (control rats were treated with vehicle and then PLZ). The
      possibility that hydroxylation in the para-position might be a metabolic route
      for PLZ has led to interest in the possible use of analogues in which this
      position is blocked with a substituent. In preliminary acute studies at a dose of
      0.1 mmol/kg p-chloro-PLZ was found to have a similar effect to PLZ on the
      inhibition of MAO and to lead to an elevation of catecholamines and 5
      hydroxytryptamine (5-HT) in rat whole brain.

PMID- 1982448
TI  - Taxol content in bark, wood, root, leaf, twig, and seedling from several Taxus
      species.
AB  - Taxol content in various parts of several Taxus species have been determined. The
      weight percent ranged from 0.00003 to 0.069.

PMID- 1982449
TI  - Impairment of cell-mediated immune responses in HTLV-I-associated myelopathy.
AB  - In order to assess in vivo cell-mediated immune functions in HTLV-I-associated
      myelopathy (HAM), we immunized 18 HAM patients with dinitrochlorobenzene (DNCB).
      Of 18 patients, the skin reaction to DNCB was negative in 15. All those 15
      patients also showed anergy to PPD-tuberculin and 9 of 15 patients had a
      persistent lymphocytopenia (less than 1500/mm3). In vitro lymphoproliferative
      responses to mitogens, assayed by a flow fluorocytometric method, were also
      significantly depressed in HAM patients when compared to normal controls. The
      results thus indicate that cell-mediated immune functions are significantly
      impaired in HAM patients.

PMID- 1982450
TI  - Mapping of von Hippel-Lindau disease to chromosome 3p confirmed by genetic
      linkage analysis.
AB  - Genetic linkage studies were performed in 12 British families with von Hippel
      Lindau disease (VHL) using RFLPs at three loci (DNF15S2, THRB, RAF1) on the short
      arm of chromosome 3. Linkage was detected between the VHL disease locus and RAF1
      with a maximum lod score of 3.88 at a recombination fraction of 0.05 (confidence
      interval 0.003-0.18). Multipoint linkage analysis suggested that the most likely
      location for the VHL disease locus is telomeric to THRB. These results confirm
      earlier reports localizing the VHL gene to the short arm of chromosome 3, and
      provide no evidence for genetic heterogeneity.

PMID- 1982451
TI  - Immunological abnormalities in family members of patients with IgA nephropathy.
AB  - We examined several immunological parameters such as the number of T cells with
      CD4 antigen and the receptor for the Fc portion of IgA (T alpha cells), in vitro
      immunoglobulin production by peripheral blood lymphocytes with or without
      pokeweed mitogen and serum levels of immune complexes in 19 healthy family
      members of patients with IgA nephropathy (IgAN). It was shown that the levels of
      serum IgA, T4 cells, CD4/CD8 ratio of T cell subsets, T alpha cells, IgA
      circulating immune-complexes and spontaneous synthesis of immunoglobulins were
      significantly increased in family members of patients with IgAN. No family
      members had proteinuria or hematuria. It was concluded that immunological
      abnormalities, including abnormalities of T cells and B cells, were found not
      only in patients with IgAN but also in their healthy family members. It was
      suggested that some factors in addition to these immunological abnormalities may
      be involved in the development of IgAN.

PMID- 1982452
TI  - Immunological abnormalities in HTLV-I-associated myelopathy: spontaneous release
      of interleukin-2 and interleukin-2 receptor by peripheral blood lymphocytes.
AB  - Ten patients with human T lymphotropic virus type I-associated myelopathy (HAM),
      5 asymptomatic HTLV-I carriers and 11 healthy normal volunteers were studied to
      determine if peripheral blood lymphocytes spontaneously release IL-2 and soluble
      IL-2 receptors. Peripheral blood lymphocytes obtained from HAM patients
      proliferated spontaneously when cultured for 5 days in vitro. Proliferating cells
      were CD3+ lymphocytes and both CD4+ cells and CD8+ cells as shown by morphologic
      and immunohistochemical observations. These T cell responses were also found in
      asymptomatic carriers, but the responses were not as marked as those of HAM
      patients. IL-2 activity in the culture supernatants was much higher in HAM
      patients than in asymptomatic carriers; IL-2 activity correlated well with the
      intensity of spontaneous proliferation of lymphocytes. Furthermore, soluble IL-2
      receptors in the cell-free supernatants from HAM patients were markedly increased
      compared to those from asymptomatic carriers. These results indicate that
      spontaneous proliferation of T cells is intimately related to HTLV-I infection
      and is probably due to autocrine or paracrine pathways which involve IL-2 and IL
      2 receptor system.

PMID- 1982453
TI  - Aging and ATPase activities in rat jejunum.
AB  - In addition to the well-known (Na,K)-ATPase activity, an ouabain-insensitive Na
      ATPase has been evidenced in the basolateral membrane of intestinal and renal
      cells from different mammals. Basolateral membranes of jejunal enterocytes from
      rats of different ages, i.e., very young, young, adult and old were separated by
      self-orienting, Percoll-gradient centrifugation. The total protein content and
      both Na- and (Na,K)-ATPase activities in initial homogenate and final pellets
      were analyzed. The dry weight of homogenate and pellet was also determined. The
      two ATPase activities and the protein content of the basolateral membrane
      fraction decrease with age when referred to the dry weight of the pellet. This
      diminution is also evident in the initial homogenate. The activation curve of Na
      ATPase, hyperbolic in shape, gives Km and Vmax values unaffected by aging. The
      same behaviour is true for the kinetic parameters of (Na,K)-ATPase, which has a
      sigmoidal velocity curve. From these results, it seems that both Na- and (Na,K)
      ATPase have the same characteristics in the basolateral membrane of the
      enterocyte throughout the life span of the animal, but they decrease
      quantitatively with aging.

PMID- 1982454
TI  - Structure, localization and function of FanF, a minor component of K99 fibrillae
      of enterotoxigenic Escherichia coli.
AB  - The DNA sequence of the K99 fanF gene, encoding FanF, was determined. An open
      reading frame of 999 bp was found. The primary structure of FanF was deduced and
      analysis revealed the presence of a signal sequence of 22 amino acid residues.
      The mature protein contains 311 amino acid residues (Mr 33,905 D). The amino acid
      sequence of FanF showed similarity with the K88ab major subunit FaeG. A specific
      mouse antiserum against FanF was prepared by constructing and purifying a hybrid
      Cro-LacZ-FanF protein. Minicell analysis, immunoblotting and
      immunoelectronmicroscopy revealed a pool of FanF in the periplasm of K99
      producing cells and showed, furthermore, that FanF is a minor component of K99
      fibrillae, present at the top and in or along the shaft of the K99 fibrillar
      structures. A fanF mutant plasmid was constructed. Cells harbouring this plasmid
      produced all K99-specific proteins, except FanF, but produced 0.1% of the K99
      fibrillae relative to 'normal' K99-producing cells. Electron microscopic
      observations showed that cells defective in fanF produce only a few (apparently
      short) K99 fibrillae. FanF, therefore, was supposed to play a role in initiation
      and elongation of K99 fibrillae formation. Thin-layer chromatography experiments
      involving purified receptor material showed that FanF is not required for binding
      of K99 fibrillae to the ganglioside receptor. Fibrillae produced by an adhesion
      negative strain carrying a mutation in the K99 major fibrillar subunit were shown
      to contain a normal amount of FanF.

PMID- 1982455
TI  - Characterization of the type 1 fimbrial subunit gene (fimA) of Serratia
      marcescens.
AB  - The nucleotide sequence of a DNA fragment that contains the fimA gene, encoding
      the major fimbrial subunit, of Serratia marcescens IA506 and associated flanking
      sequences has been elucidated. In addition, the origin of transcription has been
      identified and is located 120 base pairs upstream of the fimA initiation codon.
      The predicted amino acid sequence of the FimA polypeptide exhibits some degree of
      sequence homology with the fimbrial subunits encoded by the fimA determinants of
      Klebsiella pneumoniae, Salmonella typhimurium, and Escherichia coli and also to
      Smf2, the major structural component of mannose-resistant (MR) fimbriae of S.
      marcescens. The Serratia adhesin that facilitates haemagglutination mediated by
      type 1 fimbriae is less susceptible to inhibition by D-mannose than has been
      observed to be the case in other type 1 fimbrial adhesins. The molecule
      conferring this adherence specificity has been shown to be distinct from the fimA
      gene product and, therefore, is analogous to the fimbrial systems reported in
      other species.

PMID- 1982456
TI  - Glutamate receptor changes in brain synaptic membranes from human alcoholics.
AB  - Brains from human alcoholics and non-alcoholics were obtained shortly after
      death. The hippocampus was dissected, homogenized, and processed for the
      isolation of a synaptic membrane-enriched fraction and the study of L
      [3H]glutamic acid and 3-((+-)-2-carboxypiperazin-4-yl)-[1,2(3H)propyl-1
      phosphonic acid ([3H]CPP) binding sites. The pharmacological characteristics of L
      [3H]glutamic acid binding to synaptic membranes isolated from hippocampus
      corresponded to the labeling of a mixture of N-methyl-D-aspartate (NMDA), kainate
      and quisqualic acid receptor sites. Synaptic membranes prepared from the
      hippocampus of individuals classified as alcoholics had significantly higher
      density of glutamate binding sites than identically prepared membranes from non
      alcoholic individuals. In addition, there was a clear definition of a population
      of L-glutamate binding sites (approx. 10% of total) in the membranes from
      alcoholics that had a higher affinity for the ligand than the major set of sites
      labeled in membranes from both alcoholics and non-alcoholics. Neither the age of
      the individuals at the time of death nor the time that elapsed between death and
      processing of brain tissue were significant factors in determining either
      recovery of purified synaptic membranes from brain homogenates or L-[3H]glutamate
      binding to synaptic membranes. In order to determine whether some of the changes
      in L-[3H]glutamic acid binding were due to alterations in binding at the NMDA
      receptor subtype, we also measured binding of [3H]CPP to extensively washed crude
      synaptosomal membranes. Membranes from brains of alcoholics had higher affinity
      (3-fold) for [3H]CPP but lower binding capacity (3-fold) when compared with those
      of non-alcoholics.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1982457
TI  - Alterations in synaptosomal neurotransmitter amino acids in "petit-mal" rats at a
      daytime and a nighttime.
AB  - The synaptosomal fractions of 6 brain areas-olfactory tubercles (OT), frontal
      cortex (FC), striatum (Sr), amygdala (A), thalamus (Th), hypothalamus (Hy) - have
      been analyzed for their neurotransmitter amino acids (AA) content in Wistar rats
      exhibiting "petit-mal" epilepsy (PM-E) and in controls (C). The analysis was
      carried out at 11 p.m. (nighttime corresponding to the acrophase for the hourly
      number of spike-wave complexes) and at 11 a.m. (daytime). A day versus night
      rhythmicity is recorded for synaptosomal inhibitory AA in control and in PM-E
      rats. However, day versus night variations are more frequent and more prominent
      in C rats than in PM-E rats. Two day versus night variations exist only in PM-E
      rats: increases of GABA level in Sr and of Asp in Hy. Differences between PME-and
      C in synaptosomal AA content are more likely to be present during the nighttime.
      During this period lower AA values for PM-E rats are found for one or several
      inhibitory AA in OT, Th, and FC. It seems that the differences between PM-E and C
      concerning the inhibitory AA correlate with the number of spike-wave discharges.
      Only in one brain area is there a similar difference for PM-E and C during
      daytime and nighttime: a decreased GABA content for PM-E rats in OT. The decrease
      is larger in nighttime than in daytime. This difference may serve as a marker for
      this epileptic disorder. Moreover, it is in OT that the greatest number of PM-E
      versus C differences in synaptosomal neurotransmitter AA are observed.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1982458
TI  - Somatostatin acts through G-proteins on dopaminergic adenylate cyclase in the
      caudate-putamen of the rat.
AB  - Somatostatin was incubated in an adenylate cyclase assay of a particulate
      fraction of caudate-putamen tissue of the rat in order to examine the effect of
      the peptide on D-1 receptor coupled adenylate cyclase in vitro. Somatostatin was
      able to enhance cyclic AMP formation in the presence of guanylylimidodiphosphate
      and guanosine-triphosphate. In contrast to this, somatostatin inhibited both
      dopamine and forskolin-stimulated cyclic AMP accumulation. Pertussis toxin and
      cholera toxin also depressed forskolin-induced stimulation. Somatostatin was
      found to antagonize these inhibitory effects of pertussis toxin and cholera
      toxin. The results suggest that somatostatin acts through a stimulatory as well
      as an inhibitory guanine nucleotide regulatory protein subtype to affect
      dopaminergic adenylate cyclase activity.

PMID- 1982459
TI  - Effect of 8-bromo-cAMP and dexamethasone on glutamate metabolism in rat
      astrocytes.
AB  - Glutamine synthetase (GS) activity in cultured rat astrocytes was measured in
      extracts and compared to the intracellular rate of glutamine synthesis by intact
      control astrocytes or astrocytes exposed to 1 mM 8-bromo-cAMP (8Br-cAMP) + 1
      microM dexamethasone (DEX) for 4 days. GS activity in extracts of astrocytes
      treated with 8Br-cAMP + DEX was 7.5 times greater than the activity in extracts
      of control astrocytes. In contrast, the intracellular rate of glutamine synthesis
      by intact cells increased only 2-fold, suggesting that additional intracellular
      effectors regulate the expression of GS activity inside the intact cell. The rate
      of glutamine synthesis by astrocytes was 4.3 times greater in MEM than in HEPES
      buffered Hank's salts. Synthesis of glutamine by intact astrocytes cultured in
      MEM was independent of the external glutamine or ammonia concentrations but was
      increased by higher extracellular glutamate concentrations. In studies with
      intact astrocytes 80% of the original [U-14C]glutamate was recovered in the
      medium as radioactive glutamine, 2-3% as aspartate, and 7% as glutamate after 2
      hours for both control and treated astrocytes. The results suggest: (1)
      astrocytes are highly efficient in the conversion of glutamate to glutamine; (2)
      induction of GS activity increases the rate of glutamate conversion to glutamine
      by astrocytes and the rate of glutamine release into the medium; (3) endogenous
      intracellular regulators of GS activity control the flux of glutamate through
      this enzymatic reaction; and (4) the composition of the medium alters the rate of
      glutamine synthesis from external glutamate.

PMID- 1982460
TI  - Delta and kappa opiate receptors in primary astroglial cultures from rat cerebral
      cortex.
AB  - The effects of mu, delta, and kappa receptor-agonists on forskolin stimulated
      cyclic adenosine-3',5'-monophosphate (cAMP) formation were examined in astroglial
      enriched primary cultures from the cerebral cortex of newborn rats. Intracellular
      cAMP accumulation was quantified by radioimmunoassay. Morphine was used as a mu
      receptor agonist, D-Ala-D-Leu-Enkephalin (DADLE) as a delta-receptor agonist and
      dynorphin 1-13 (Dyn) as a kappa-receptor agonist. Basal cAMP levels were
      unaffected by either the opiate agonists or the antagonists used. In the presence
      of the cAMP stimulator forskolin, morphine had no significant effect on the
      cytoplasmic cAMP levels. DADLE caused a dose related inhibition of the forskolin
      stimulated cAMP accumulation. The effects of this delta receptor stimulation was
      blocked with the selective antagonist ICI 174.864. In the presence of Dyn, the
      forskolin stimulated cAMP accumulation was inhibited in a dose related manner.
      This kappa receptor stimulation was blocked with the selective antagonist MR
      2266. Co-administration of DADLE and Dyn resulted in a non additive inhibition of
      the forskolin stimulated accumulation of cAMP. These findings indicate that
      astroglial enriched cultures from the cerebral cortex of rats express delta and
      kappa-receptors co-localized on the same population of cells, and that these
      receptors are inhibitory coupled to adenylate cyclase.

PMID- 1982461
TI  - Effects of two microtubule-depolymerizing drugs, vincristine and vinblastine, on
      porphyrin production by primary neural tissue cultures.
AB  - A porphyrinogenic effect of 10(-5) to 10(-7) M Vincristine (VC) and Vinblastine
      (VB) was observed on primary neural tissue cultures prepared from chicken embryo
      brain in the presence of 10(-3) M delta-aminolevulinic acid. This effect is very
      pronounced in neurocyte cultures, in contrast with the documented neurite
      elongation defect. The microtubule disassembly by VC and VB changed the quantity
      of the porphyrins in the cells and medium of glial cell cultures. The correlation
      was studied between the depolymerization of the microtubules by VC and VB and the
      porphyrin overproduction of primary neural tissue cultures, the investigation
      also extending to 10(-7) M taxol. The direct mediation of nucleotide binding
      proteins of the adenyl-cyclase complex by GTP liberated from beta-tubulin during
      the disassembly of the microtubules is presumed.

PMID- 1982462
TI  - Hippocampal levels of dynorphin A (1-8) in neonatal and 16-week-old spontaneously
      hypertensive rats: comparisons with DOCA-salt hypertension.
AB  - In this study the possible role of hippocampal dynorphin in the development of
      hypertension in spontaneously hypertensive rats (SHR) was investigated by
      determining dynorphin A (1-8) (DN A (1-8] levels in hippocampus in 16 week old
      SRH, Wistar Kyoto (WKY) controls and SHR treated with antihypertensive drugs as
      well as DOCA-salt hypertensive Sprague Dawley (SD) rats, using radioimmunoassay
      (RIA). We found that DN A (1-8) was decreased significantly in both dorsal (-68%)
      and ventral (-58%) hippocampus in SHR compared with WKY rats. Treatment with
      hydralazine and guanethidine (25 mg/kg/24 hr of each drug in drinking water) for
      8 weeks to prevent the development of hypertension in young SHR had no effect on
      this low hippocampal dynorphin level. We failed to find significant changes in
      hippocampal DN A (1-8) level in DOCA-salt hypertensive rats. The low level of
      hippocampal dynorphin existed before the development of hypertension in 6 day
      neonatal SHR (-73%). Hippocampal Met-enkephalin was unchanged in all experimental
      groups except for a slight decrease in neonatal SHR. The results establish a
      genetic difference in the hippocampal dynorphin system of SHR compared with WKY,
      the significance of which, for the development of hypertension, remains to be
      investigated.

PMID- 1982463
TI  - Quantitative radioautographic study of somatostatin receptors heterogeneity in
      the rat extrahypothalamic brain.
AB  - The possible heterogeneity of extrahypothalamic somatostatin receptors was
      studied in rat brain by quantitative radioautography. The respective distribution
      and relative proportion of two somatostatin receptor sub-types (SS1 and SS2) were
      assessed by using two radioligands, the non-selective probe [125I]Tyr3-D-Trp8
      somatostatin14 and the SS1 selective analogue [125I]Tyr3-SMS 201-995. For both
      ligands, adjacent brain sections were processed in the presence of micromolar
      concentrations of either a non-discriminative competitor (somatostatin14) or SS1
      selective analogue (SMS 201-995). The comparative analysis of the specific
      binding remaining in the presence of each non-radioactive competitor permitted a
      semi-quantitative analysis of the proportion of SS1 and SS2 receptor sub-types in
      each brain region examined. Data obtained correlate well with homogenate binding
      results reported previously [Reubi J. C. (1984) Neurosci. Lett. 49, 259-263].
      Although the distribution patterns obtained with both radioligands were similar,
      [125I]Tyr3-SMS 201-995 labelled only a fraction of [125I]Tyr0-D-Trp8
      somatostatin14-labelled sites in certain brain regions. For example, both
      superficial and deep cortical laminae, as well as the basolateral amygdaloid
      nucleus and CA1 hippocampal area exhibited different binding densities with
      [125I]Tyr0-D-Trp8-somatostatin14 depending on the competitor used in the assay
      (somatostatin14 or SMS 201-995). On the other hand, [125I]Tyr3-SMS 201-995
      binding was eliminated in an identical fashion by either competitor in these very
      same brain areas. This suggests the existence of SS1 and SS2 somatostatin
      receptor sub-types in these regions. In all other brain areas examined,
      somatostatin receptor sites are apparently of the SS1 sub-type. The heterogeneity
      of somatostatin receptors observed in certain regions may have relevance for the
      various biological effects induced by somatostatin in the central nervous system.

PMID- 1982464
TI  - Effects of acetylcholine on single cortical somatosensory neurons in the
      unanesthetized rat.
AB  - Experiments have been performed on unanesthetized rats using a chronic restraint
      system. The animal's head was held in a stereotaxic apparatus by means of two
      metallic tubes fixed on the skull with dental cement. Electrodes consisted of a
      recording micropipette (filled with 1 M NaCl and 2% Pontamine Blue) attached to a
      multibarreled micropipette for iontophoresis. Electrode penetrations were
      reconstructed on camera lucida drawings of frontal brain sections. The overall
      percentage of spontaneously active somatosensory neurons was 77% with a mean
      spontaneous activity of 5.9 impulse/s (n = 405). Yet differences were observed in
      the proportions of active cells as well as in the mean spontaneous activity
      between cortical layers (both parameters being significantly higher in layers V
      and VI). Comparison with results obtained under urethane anesthesia [Dykes R. W.
      and Lamour Y. (1988) J. Neurophysiol. 60, 703-724] shows that the percentage of
      the spontaneously active neurons and the mean spontaneous activity were both
      significantly higher in unanesthetized rats (77 vs 36%; 5.9 vs 2.6 impulse/s).
      Nevertheless, the laminar distribution of the most active cells was similar under
      both conditions. In the present study, 52.3% of the neurons (n = 380) were
      excited by acetylcholine and 46% (n = 198) by carbachol. Significantly larger
      percentages of neurons excited by acetylcholine were found in layers Vb and VIb.
      These effects of cholinergic agonists--observed for the first time in
      unanesthetized rats--differed significantly from those previously obtained under
      anesthesia (33 and 34% of neurons excited by acetylcholine and carbachol,
      respectively) [Lamour Y. et al. (1982) Neuroscience 7, 1483-1494].(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1982465
TI  - Quantitative autoradiographic analysis of glutamate binding sites in the
      hippocampal formation in normal and schizophrenic brain post mortem.
AB  - Using quantitative autoradiography, the anatomical distribution of the binding
      sites (kainate, N-methyl-D-aspartate and quisqualate) for the excitatory
      neurotransmitter glutamate has been established in the hippocampal formation from
      control and schizophrenic brains, post mortem. There is a loss of the kainate
      subtype particularly in schizophrenic hippocampi mainly from the CA4/CA3 mossy
      fibre termination zone of the cornu ammonis (CA4 and CA3; control and
      schizophrenic left hippocampus, respectively, 54.2 and 66.6 pmol/g; 18.3 and 17.9
      pmol/g), as well as bilateral losses in the dentate gyrus (left 14.2 pmol/g and
      right 28.0 pmol/g; left 9.5 pmol/g and right 7.9 pmol/g, control and
      schizophrenic, respectively) and parahippocampal gyrus (left 50.8 pmol/g and
      right 41.7 pmol/g, left 27.7 pmol/g and right 25.3 pmol/g, control and
      schizophrenic, respectively). There is complete preservation of N-methy-D
      aspartate sites in schizophrenic hippocampi, and a marginally significant loss of
      the quisqualate binding site in CA4/CA3 regions (left 249 fmol/g and right 306
      fmol/g, left 157 fmol/g and right 148 fmol/g, control and schizophrenic,
      respectively). These findings reflect the possible importance of glutamate in the
      pathophysiology of schizophrenia and represent novel targets for therapeutic
      manipulation in schizophrenia.

PMID- 1982466
TI  - Neuromodulatory effects of corticotropin releasing factor on cerebellar Purkinje
      cells: an in vivo study in the cat.
AB  - Corticotropin releasing factor, a 41 amino acid peptide, has been localized in
      climbing fibers and mossy fibers in the cat's cerebellar cortex. In the present
      study, corticotropin releasing factor was iontophoretically applied to Purkinje
      cells, isolated extracellularly, to assess the effect of this peptide on the
      firing rate of the neuron. By itself corticotropin releasing factor had little or
      no effect on cellular activity. However, this peptide potentiated the excitatory
      effects of aspartate and glutamate, the putative neurotransmitters of the
      climbing fiber and mossy fiber-parallel fiber systems, respectively. In addition,
      corticotropin releasing factor blocked the suppressive effects induced by the
      iontophoretic application of GABA. Finally, it shortened or eliminated the period
      of suppression produced by activation of climbing fibers in the cerebellar
      cortex. These data suggest that corticotropin releasing factor functions as a
      neuromodulator rather than as a neurotransmitter in cerebellar circuitry.

PMID- 1982468
TI  - Augmentation by glycine and blockade by 6-cyano-7-nitroquinoxaline-2,3-dione
      (CNQX) of responses to excitatory amino acids in slices of rat neocortex.
AB  - Responses of neocortical pyramidal cells to excitatory amino acids were recorded
      intracellularly. Agonists and antagonists were applied electrophoretically from a
      separate multibarrel pipette and care taken to ensure that the pipette was
      positioned to evoke optimal responses to N-methyl-D-aspartate (NMDA), or
      homocysteic acid, before control responses were recorded. Responses to NMDA, but
      not those to alpha-amino-3-hydroxy-5-methyl-4-isoxazdepropionic acid (AMPA) or
      quisqualate, were enhanced when glycine was co-applied. Responses to AMPA,
      quisqualate and NMDA were reduced by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)
      applied either electrophoretically, or in the bathing medium, with responses to
      quisqualate being the least and those to AMPA being the most sensitive to CNQX.
      The blockade of NMDA responses by CNQX was selectively reversed by additional
      glycine confirming that CNQX blocks NMDA receptor-channel complexes at the
      glycine, rather than at the NMDA site. Under control conditions, responses to
      glutamate resembled responses to quisqualate, and were relatively insensitive to
      CNQX, 3-((+/-)-2-carboxypiperazin-4-yl)-propyl-l-phosphonic acid and 2-amino-5
      phosphonovalerate, while responses to homocysteic acid resembled responses to
      NMDA and were blocked by these antagonists. This suggested that homocysteic acid
      acted at NMDA receptors, while glutamate acted primarily at non-NMDA receptors.
      However, responses to both glutamate and homocysteic acid were augmented by
      additional glycine when these transmitter candidates were applied close to a "hot
      spot" for NMDA receptor activation. The glycine enhancement of responses to
      glutamate was sensitive to NMDA antagonists, indicating that glutamate can
      activate NMDA receptors in an intact preparation if glycine levels are high
      enough.

PMID- 1982467
TI  - The role of D1 and D2 dopamine receptors in oral stereotypy induced by
      dopaminergic stimulation of the ventrolateral striatum.
AB  - Microinjection of amphetamine into the ventrolateral region of the striatum
      results in compulsive and intense oral stereotypies in the rat. Although these
      stereotyped behaviors are known to be a direct result of excessive stimulation of
      the striatal dopamine neurons, the relative roles of the D1 and D2 receptors in
      oral stereotypies are not clearly understood. It is reported here that
      microinjection of the selective D1 agonist, SKF 38393 (0, 0.3, 3.0, 30.0
      micrograms in 0.5 microliters vehicle) into the ventrolateral striatum resulted
      in no observable changes in behavior during the 30-min test period. However, it
      was observed that intense self-biting emerged 3-4 h following injection.
      Examination of histology from these animals revealed extensive tissue damage and
      the delayed onset of biting was hypothesized to result from a neurotoxic effect
      of SKF 38393. Infusion of quinpirole (0, 0.3, 3.0, 30.0 micrograms in 0.5
      microliter vehicle), a selective D2 agonist, resulted in a dose-dependent
      increase in orofacial behaviors such as licking, wood-chip eating, head-down
      sniffing and mouth movements. Intense oral stereotypies such as biting or gnawing
      were not observed following treatment with quinpirole. Infusion of the mixed
      agonist dopamine (0, 2.0, 10.0, 20.0 micrograms in 0.5 microliter vehicle) into
      the ventrolateral striatum was found to elicit intense oral stereotypy. This
      behavior consisted almost exclusively of self-biting similar to that observed
      following amphetamine microinjection into this region. Haloperidol, when given as
      either a systemic (0.2 mg/kg) or intra-ventrolateral striatum (2.5 micrograms/0.5
      microliter) pretreatment, effectively blocked oral stereotypies induced by
      amphetamine microinjection into the ventrolateral striatum. Pretreatment with
      either the D1 antagonist SCH 23390 (0, 0.01, 0.1 mg/kg, i.p.) or the D2
      antagonist raclopride (0, 0.05, 0.50, 1.0 mg/kg, i.p.) antagonized amphetamine
      induced oral stereotypy in a dose-dependent manner. These findings demonstrate
      that within the striatal site specifically implicated in oral behavior,
      concurrent stimulation of both receptor subtypes is necessary for the expression
      of intense oral stereotypies.

PMID- 1982470
TI  - Synthesis, pharmacological investigations and X-ray studies on new 4,5-dihydro-1H
      2,4-benzodiazepine derivatives.
AB  - The synthesis and biological activity of a series of 4,5-dihydro-1H-2,4
      benzodiazepine is reported. The structure-activity relationship of these new
      compounds was studied based on X-ray investigations. Pharmacological
      investigations have shown that the compounds exert depressive action on the
      central nervous system and exhibit weak neuroleptic activity.

PMID- 1982469
TI  - Dopaminergic interplexiform cells displaced to the ganglion cell layer in the rat
      retina.
AB  - The reconstruction of dopaminergic interplexiform cells visualized by their
      tyrosine hydroxylase immunoreactivity in rat retinal wholemounts demonstrates
      that the immunoreactive processes observed in the inner nuclear and outer
      plexiform layers can belong to dopaminergic cell bodies located in the ganglion
      cell layer. An example of such a displaced interplexiform cell has been analyzed
      by camera lucida drawings, micrographic focal series and computer rotations.

PMID- 1982471
TI  - WHO consultation with women NGOs on AIDS.

PMID- 1982473
TI  - Future perspectives for comprehensive blood gas analysis. Second workshop.
      Copenhagen, 1989.

PMID- 1982472
TI  - World AIDS day 1990 to focus on women.

PMID- 1982474
TI  - [Spontaneous rupture of the kidneys in hemorrhagic fever with renal syndrome].
AB  - During the recent 5 years we had 29 patients with hemorrhagic fever and renal
      syndrome complicated by a spontaneous kidney rupture. This complication occurred
      during an anuric period in 18 patients and within the first 24 hours of restored
      diuresis in 11 patients. Major clinical presentations of the kidney rupture were
      deterioration of lumbar and abdominal pains, meteorism and symptoms of an
      internal bleeding. Palpation revealed hematoma at the site of the ruptured
      kidney, tension of the anterior abdominal wall and symptomatic peritoneal
      irritation. Diagnosis of spontaneous kidney rupture in hemorrhagic fever with the
      renal syndrome (HFRS) relies on clinical, laboratory and ultrasound studies.
      Additional studies are plain urography and retroperitoneal diagnostic puncture of
      the affected site. Conservative therapy was given to 11 patients with erythrocyte
      counts of 3 x 10(12)/l or higher. The treatment was operative in 18 patients.
      Indications for surgery were progressive anemia, a palpable retroperitoneal
      hematoma and symptomatic peritoneal irritation. All patients underwent evacuation
      of blood clots and ligation of the renal ruptures. In the authors' opinion, renal
      decapsulation and pyelostomy are useful in this condition. Bilateral involvement
      and severe renal failure are contraindications for nephrectomy in HFRS. It may be
      used only as a last resort in life-threatening bleeding.

PMID- 1982475
TI  - [Changes in the level of unsaturated fatty acids in rheumatoid arthritis patients
      during treatment].
AB  - Patients with rheumatoid arthritis showed changes of the fatty acid spectrum
      manifested in a reduction of the polyunsaturated acids (linoleic, linolenic,
      arachidonic) and an increase of the level of monounsaturated (oleic,
      palmithooleinic) depended on the course of the disease. Antirheumatic treatment
      produced a positive effect, especially gold preparations, on normalization of the
      level of unsaturated fatty acids in rheumatoid arthritis.

PMID- 1982476
TI  - Selective opening of the blood-tumour barrier by intracarotid infusion of
      leukotriene C4.
AB  - Intracarotid infusions of leukotriene C4 (LTC4) were used to selectively open the
      blood-tumour barrier in rats with RG-2 gliomas. Blood-brain and blood-tumour
      barrier permeability was determined by quantitative autoradiography using 14C
      aminoisobutyric acid. LTC4 (4 micrograms total dose) infused into the carotid
      artery ipsilateral to the tumour increased the unidirectional transfer constant
      for permeability, Ki, two-fold within the tumour while no effect on permeability
      was seen in the normal brain. No gamma glutamyl transpeptidase (gamma-GTP)
      activity was seen in tumour capillaries in contrast to high gamma-GTP in normal
      brain capillaries. These findings suggest that normal brain capillaries may
      resist the vasogenic effects of LTC4 while LTC4 will increase permeability in
      tumour capillaries. This could relate to the ability of gamma-GTP to act as an
      enzymatic barrier and inactivate leukotrienes in normal brain capillaries.
      Intracarotid LTC4 infusion may be a useful tool to selectively open the blood
      tumour barrier for delivery of antineoplastic compounds.

PMID- 1982477
TI  - Excitatory amino acid receptors, oxido-reductive processes and brain oedema
      following transient ischaemia in gerbils.
AB  - A key mechanism of brain injury after cerebral ischaemia is supposed to be the
      iron-dependent formation of highly reactive oxygen free radicals initiated by the
      intracellular accumulation of calcium and promoted by the excess release of
      glutamate. Oxido-reductive processes (formation of superoxide radicals and lipid
      peroxidation) are mediated through NMDA-receptors, while non-NMDA receptors,
      associated with (or being a part of) Na,K-ATPase, are responsible for
      postischaemic brain swelling. The hypothesis was put forward for consideration
      that release of glutamate (and other related endogenous excitatory amino acids)
      due to depolarization in the early minutes of ischaemia and (non)-NMDA
      antagonists may have roles in the development and prevention of metabolic brain
      impairment and cytotoxic oedema, respectively, in the ischaemic state.

PMID- 1982478
TI  - Role of neuroexcitation in development of blood-brain barrier and oedematous
      changes following cerebral ischaemia and traumatic brain injury.
AB  - Potential involvement of neuroexcitatory mechanisms was studied in: 1) repetitive
      forebrain ischaemia in gerbils, 2) global cerebral ischaemia in rats and 3)
      cryogenic injury to the cerebral cortex in rats and gerbils. Uptake of 45Ca was
      used as a marker of injury, whereas ultrastructural localization of calcium was
      assessed with an oxalate-pyroantimonate method. The blood-brain barrier was
      evaluated with immunostaining for serum albumin. Changes in extracellular
      glutamate were estimated by microdialysis and an enzymatic cycling assay. Changes
      in water content were assessed by specific gravity measurements. Repetitive
      ischaemia of 3 x 5 min carotid occlusions produced a cumulative effect with
      regard to development of oedema and neuronal injury. This was associated with
      several-fold increments in glutamate release after repeated insults, whereas
      there was no apparent correlation with energy metabolism disturbances. Other
      studies revealed in all models a development of secondary foci distant to the
      primary impact of ischaemia or cold lesions, which were characterized by calcium
      accumulation in swollen dendrites, chronic neuronal changes and intraneuronal
      uptake of serum proteins, all of these changes being potentially compatible with
      involvement of neuroexcitatory mechanisms.

PMID- 1982479
TI  - Effect of glutamate and its antagonist on shift of water from extra- to
      intracellular space after cerebral ischaemia.
AB  - The effects of glutamate and the excitatory amino acid antagonist, MK-801, were
      investigated on the time course of the shift of water from extracellular to
      intracellular space (progression or cytotoxic oedema) after total brain ischaemia
      in rats. Administration of sodium glutamate intravenously before ischaemia
      accelerated the shift of water dose-dependently. On the contrary, preischaemic
      administration of MK-801, an NMDA antagonist, delayed the progression of
      cytotoxic oedema due to brain ischaemia. We consider that glutamate and NMDA
      antagonists may have important roles in the development and prevention of
      cytotoxic oedema in the ischaemic state.

PMID- 1982480
TI  - Attenuation of glutamate-induced neuronal swelling and toxicity in transgenic
      mice overexpressing human CuZn-superoxide dismutase.
AB  - The role of oxygen-derived free radicals, superoxide in particular, in the
      pathogenesis of neuronal cell death induced by glutamate was studied using
      primary culture cortical neurons from transgenic mice overexpressing human CuZn
      superoxide dismutase. Primary cortical neuron cultures were developed form 15-day
      old fetuses of both transgenic mice and their normal littermates. Both human CuZn
      superoxide dismutase and host mouse CuZn-superoxide dismutase activities in
      cultured neurons were identified by native gel electrophoresis followed by
      nitroblue tetrazolium staining. Cultured neurons grown for 10-12 days in vitro
      were exposed briefly to 0.5 mM glutamate for 5 minutes, followed by biochemical
      and morphological examinations at 2 and 4 hours. Our data have demonstrated that
      glutamate neurotoxicity is significantly reduced in transgenic neurons at 2 and 4
      hours following exposure to glutamate, as measured by the intracellular 3-0
      methyl glucose space, the efflux of lactate dehydrogenase, and by phase-contrast
      and bright-field trypan blue staining. These data indicate that transgenic
      neurons containing two- to threefold the normal amount of CuZn-superoxide
      dismutase activity are protected against glutamate neurotoxicity in vitro. Our
      results suggest that oxidative stress play an important role in glutamate-induced
      neuronal swelling and toxicity.

PMID- 1982481
TI  - Changes in extracellular glutamate concentration after acute subdural haematoma
      in the rat--evidence for an "excitotoxic" mechanism?
AB  - Using a rat model of subdural haematoma which is associated with ischaemic damage
      in the ipsilateral hemisphere, we have measured cerebral blood flow and release
      of excitatory amino acids after the haematoma. A more than sevenfold rise in
      glutamate and aspartate, persisting for forty minutes occurred in the severely
      ischaemic cortex (CBF less than 5 ml 100 gm-1 min-1) and a threefold, sustained
      rise was seen in hippocampus, although CBF was preserved (85 ml/100 g/-1 min-1).
      Excitotoxic mechanisms may, therefore, be involved in the ischaemic damage
      associated with subdural haematoma.

PMID- 1982482
TI  - Ischaemic brain damage associated with tissue hypermetabolism in acute subdural
      haematoma: reduction by a glutamate antagonist.
AB  - Ischaemia results in elevated extracellular glutamate concentrations, and drugs
      which act at the N-methyl-D-aspartate sub-type of glutamate receptor have been
      shown to decrease ischaemic brain damage. Because almost all patients who die
      after severe head injury demonstrate ischaemic brain damage, and acute subdural
      haematoma (ASDH) is one of the commonest complications of severe head injury, we
      have studied this condition in a rat model. Using double-label autoradiography,
      we have measured the effects of ASDH on cerebral glucose utilization and cerebral
      blood flow (RCBF). Following ASDH, increased glucose utilisation was observed in
      some cortical and hippocampal structures, without concomitant increases in blood
      flow. Directly below the ASDH, blood flow and glucose utilization were profoundly
      reduced. Pre-treatment with D-CPP-ene, a competitive NMDA antagonist, resulted in
      amelioration of hypermetabolism induced by the ASDH. The results suggest that
      NMDA antagonists may prevent ischaemic brain damage after ASDH by reducing
      hypermetabolism, induced by glutamatergic mechanisms.

PMID- 1982483
TI  - Glutamine synthetase inhibition prevents cerebral oedema during hyperammonemia.
AB  - The relationship between cerebral oedema and cerebral glutamine accumulation was
      investigated during acute hyperammonemia in anesthetized rats. Six hours of
      ammonium acetate infusion resulted in an increase in cortical glutamine
      concentration and a decrease in specific gravity. Pretreatment with methionine
      sulfoximine inhibited glutamine synthetase, prevented the increase in glutamine
      during hyperammonemia, and prevented the decrease in specific gravity. We
      conclude that the increase in brain water content is linked to the glutamine
      accumulation derived from the detoxification of ammonia by glutamine synthetase.

PMID- 1982485
TI  - [Prevention of nosocomial infections during resuscitation. IIIrd National
      Congress of Hospital Hygiene. Bordeaux 15-16 June 1989].

PMID- 1982484
TI  - Mechanisms underlying glutamate-induced swelling of astrocytes in primary
      culture.
AB  - The effects of glutamate and its agonists and antagonists on the swelling of
      primary astrocytes were studied. Glutamate, aspartate, homocysteate, and
      quisqualate caused a significant increase in astrocytic swelling as measured by 3
      0-methyl-[14C]-glucose uptake and by phase-contrast microscopic observations. N
      methyl-D-aspartate and kainate were not effective, nor were the competitive NMDA
      receptor antagonists. Ketamine and MK-801, the non-competitive NMDA receptor
      antagonists protected the cultured astrocytes against glutamate-induced swelling.
      Moreover, Glu-induced astrocytic swelling was significantly reduced when sodium
      ions were depleted from the culture medium. The sodium ion dependence of Glu
      induced astrocytic swelling is rather specific, since depletion of Ca2+ or Mg2+
      had no effect. Our data suggest that Na(+)-dependent, Glu-mediated cell swelling
      occurs in primary cell cultures of astrocytes.

PMID- 1982486
TI  - Restriction fragment length polymorphism identification of goat alpha s1-casein
      alleles: a potential tool in selection of individuals carrying alleles associated
      with a high level protein synthesis.
AB  - The extensive polymorphism of caprine alpha s1-casein, which is controlled by at
      least seven autosomal alleles segregating in a Mendelian fashion, was
      investigated by RFLP analysis. Genomic DNA from 77 lactating goats, whose
      genotypes had been previously determined by electrophoretic analysis of milk
      proteins, was digested with 11 restriction endonucleases and Southern blots were
      probed with a radiolabelled ovine alpha s1-casein cDNA. Three enzymes, PstI, TaqI
      and Rsa I, allowed the unambiguous identification of known alleles alpha s1-CnA,
      E and O and of the allelic pairs [alpha s1-CnD and F] and [alpha s1-CnB and C].
      Evidence for a second null allele, termed alpha s1-CnO', and for an additional
      allele, designated alpha s1-CnF', was provided, which leads to the identification
      of nine alleles at the alpha s1-Cn locus, in this species. Although only 15 out
      of the 45 expected genotypes could be fully ascertained, this procedure allows
      the identification at birth of animals carrying the alpha s1-CnA, B or C alleles
      associated with a high alpha s1- and whole-casein content.

PMID- 1982487
TI  - Synthetic cationic amphiphiles for liposome-mediated DNA transfection.
AB  - The compounds with efficient DNA transfection ability into eukaryotic cells were
      searched from various synthetic amphiphiles which have cationic heads and long
      saturated hydrocarbon tails. The efficiency of amphiphiles in gene transfer was
      examined by the transient expression of cytochrome b5 from its cDNA in COS cells.
      Among various synthetic amphiphiles, including N-[1-(2,3-dioleyloxy)propyl]-N,N,N
      trimethylammonium chloride which is commercially available lipid, O,O'-didodecyl
      N-[p-(2-trimethylammonioethyloxy)benzoyl]-(L) -glutamate bromide was highest in
      efficiency. The optimum condition for the amount of the amphiphile and DNA, and
      the incubation time were established to be 7.5-15 micrograms/22 mm dish and 1-10
      micrograms/22 mm dish, and 48-72 h, respectively.

PMID- 1982488
TI  - Structure-activity relationships in 1,4-benzodioxan-related compounds. 2. Role of
      the amine function on alpha-adrenoreceptor blocking activity.
AB  - Several WB4101 (1)-related compounds were synthesized. Their alpha-adrenoreceptor
      blocking properties were evaluated in order to understand the kind of interaction
      occurring between the amine function of (1)-related compounds and the alpha
      adrenoreceptor anionic site. The results suggest that a charge reinforced
      hydrogen bond rather than an ion pairing might play a most important role in
      receptor binding.

PMID- 1982489
TI  - Enantiomers of 8-(3-tert-butylamino-2-hydroxypropoxy)-3,4-dihydro-3-oxo-2H-
      (1,4)benzothiazine: racemic resolution, chiral synthesis and biological activity.
AB  - We report the resolution of racemic (+/-)-1 with (R)-(+)-methylbenzyl isocianate
      and the synthesis of (R)-1 and (S)-1 via Sharpless chiral epoxidation. The
      enantio- and tissue-selectivity of such enantiomers, as beta- and alpha
      adrenoceptor antagonists, were studied. Compound 1, while confirming the potent
      beta-blocking activity, displayed a modest enantio-selectivity towards beta 1-
      and beta 2-adrenoceptors. All the compounds displayed no activity as alpha
      adrenoceptor blockers.

PMID- 1982490
TI  - Restriction fragment length polymorphism for the identification of Campylobacter
      jejuni-isolates.
AB  - Companion animals ("pets") are occasionally carriers of organisms pathogenic for
      man. In the present, study fecal samples of clinically inapparent animals with
      direct contact to 204 patients, suffering from campylobacter enteritis, were
      investigated for C. jejuni or C. coli (CJC). CJC positive animals were seen in
      the environment of only five patients (= 2.4%). By comparison of biotypes and
      serotypes of thermostable and thermolabile antigens from human and animal
      isolates no clear epidemiological relationship could be deduced. Using
      chromosomal DNA of the strains, genetic identity of the isolates was studied for
      HaeIII-restriction fragment length polymorphism (RFLP), applying a biotinylated
      commercial CJ probe. The probe was found to be specific for most CJ strains and
      revealed a pattern of one to four bands. In contrast to biotyping no identity of
      patient strains and animal isolates was seen in three cases; one case with
      different biotypes had identical RFLP patterns; one patient CJ strain did not
      show any pattern with the CJ probe. Serotypes were identical for a larger number
      of animal strains but differed in HaeIII RFLP and vice versa. Comparing the
      results from the different technological approaches it seems impossible to give a
      clear statement on the epidemiology of campylobacter infections or carrier state
      by biotyping alone. It is concluded that DNA RFLP patterns are a useful
      additional tool, but for epidemiological analysis a set of different methods
      should be used.

PMID- 1982491
TI  - Elasmobranch vision: multimodal integration in the brain.
AB  - Multimodal sensory areas that include vision have been identified physiologically
      in two separate pallial areas in the telencephalon and in the tectum of the
      mesencephalon. Multisensory integration occurs in the medial pallium of the
      little skate, Raja erinacea, and a primitive squalomorph shark, Squalus
      acanthias, whereas in the advanced galeomorph shark, Ginglymostoma cirratum, a
      major multimodal area is in the dorsal pallium pars centralis. Pars centralis has
      undergone extensive hypertrophy in the evolution of advanced batoids and
      galeomorph sharks. More complete studies are required on individual species to
      assess the possibility that there has been an evolutionary shift in major sensory
      processing areas from medial to dorsal pallium among the elasmobranchs. Most
      retinofugal fibers in elasmobranchs project spatiotopically to the tectum, the
      central zone of which is an area of multimodal integration. The spatiotopic
      tectal map of the electrosense in the little skate includes only that part of the
      electrosensory field that is within the visual field, and individual points on
      the tectum represent the same spatial location in each sense. In both maps the
      region of space near the horizon is greatly overrepresented. For vision this
      corresponds to a band of increased retinal ganglion cell density, and for both
      senses the overrepresentation may be related to the importance of this region of
      space in the skate's natural orienting. Spatial congruence of visual and
      electrosensory maps should ensure that individual tectal cells integrate
      multimodal information in a space-specific fashion.

PMID- 1982492
TI  - Dynamic properties of visual evoked potentials in the tectum of cartilaginous and
      bony fishes, with neuroethological implications.
AB  - We have extended the study of Bullock ('84), who reported on visually evoked
      potentials (VEP) in the tectum of 10 species of elasmobranchs, by adding further
      stimulus regimes, multichannel recording, and additional taxa, particularly
      addressing the question of flicker fusion frequency by electrophysiological signs
      in central processing centers. Using principally the guitarfish, Platyrhinoidis
      and Rhinobatos, and the bass, Paralabrax, with some additional data from 32 other
      species, the findings support the following conclusions: 1. Latency of the first
      main VEP peak, a sharp surface negativity, to a diffuse white flash of submaximal
      intensity while the eye is moderately light adapted varies from less than 20 ms
      in some teleosts to greater than 120 ms in agnathans, holocephalans, and some
      rays. Among the elasmobranchs tested, the sharks are generally faster than the
      rays. Among the teleosts tested, some species are at least three times slower
      than others. There is little overlap between the fastest elasmobranchs and the
      slowest teleosts. 2. After the first VEP peak, later components are more diverse
      than the classic descriptions of one late surface-negative hump; they may include
      also sharp peaks, slow humps, and oscillatory waves extending out to greater than
      1 s postflash. These are highly labile, variable and similar to OFF responses
      after a long light pulse. All these components occur already in the retina,
      whether the optic nerve is intact or cut. Many records do not show the late
      components; in the same preparation, some tectal loci may and others may not. 3.
      Ongoing activity (the micro-EEG, over all frequency bands) is depressed between
      early and late waves after a flash as well as during a long light pulse. 4.
      Repeated flashes above a few per second do not so much cause fatigue of the VEPs
      as reduce or prevent them by a sustained inhibition; large late waves are
      released as a rebound excitation any time the train of flashes stops or is
      delayed or sufficiently weakened. 5. Repeated flashes depress first the early
      waves; later waves follow 1:1 up to an upper following frequency (UFF) of
      approximately 13 Hz in the guitarfishes at optimal intensity and light adaptation
      (15-17 degrees C). A transition zone of gradual fusion from 15 to 30 Hz is marked
      by sputtering or irregular sharp VEPs; above a lower fusion frequency (LFF) of 30
      40 Hz, the flash train becomes equivalent to steady light.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 1982493
TI  - Teleost vision: seeing while growing.
AB  - Teleost fish eyes grow throughout life without compromising visual performance of
      the animal. This is made possible by a set of novel adaptations in the growth and
      development of the eye. Increased retinal area is achieved both by stretching the
      existing retina and by generation of new tissue at the retinal germinal zone at
      the margin of the eye. Rods are added in a fundamentally different fashion than
      are all other retinal cell types: they appear last as new retina is produced at
      the margin and they are inserted throughout the functional retina as it
      stretches. In this way, the animal maintains a constant rod density to preserve
      vision in low light level. Because the larger eye produces a larger image, visual
      acuity improves slightly as the animal grows. Adaptations responsible for
      regulation of retinal growth are analyzed and discussed.

PMID- 1982494
TI  - Comparative biochemistry and biophysics of elasmobranch lenses.
AB  - This presentation compares the features of the lenses of sharks and skates to
      those of land animals, including man. Of all the tissues of vertebrates, the
      chemistry and physical features of the ocular lens have been preserved intact.
      Functionally, while the transmission of light and images is common to both
      classes, the elasmobranch lens shares the added task of refraction with the
      teleosts (as the cornea does not refract in the sea), and the mammal lens is
      deformed to support accommodation, while the elasmobranch lens is not. Light
      filtration by lens pigments does occur mainly in diurnal or shallow-swimming
      species. The same group of lens crystallins is present in sharks (and skates) as
      is present in squirrels (and humans). The same structural arrangement of a mono
      layer of epithelial cells anteriorly and concentric layers of differentiated and
      fiber cells from the periphery to the center apply to most vertebrates. Fiber
      cell ribbon shapes and interdigitating knobs are also very similar, as are the
      fine structures of the fiber cell membranes and the polymerized arrays of actin.
      Yet the elasmobranch lens is hard and spherical, while the mammalian lens is soft
      and disc-shaped. What the chemical basis is for the differing physical states of
      lenses of shark and man remains to be answered. This presentation will document
      the chemical and morphological bases for elasmobranch and mammal lens structure
      and function. It also will show that even though a shark is a primitive
      vertebrate, its lens is still useful as a model to assist in the understanding of
      lens aging, of lens swelling (or lack of it) and the classical basis of cataracts
      (or lack of them).

PMID- 1982495
TI  - Structural features and adaptive properties of photoreceptors in the skate
      retina.
AB  - In the duplex (rod/cone) retinae of most vertebrates, electrical responses
      associated with nocturnal vision can be recorded in relative isolation only over
      a limited intensity range before there is encroachment by signals from the cone
      system; e.g., at mesopic levels of illumination, the rods begin to saturate, and
      the cone mechanism is brought into play. On the other hand, the retinae of some
      sub-species of skate appear to contain only one class of photoreceptors, namely
      rods. Nevertheless, skate photoreceptors, as well as other retinal neurons, are
      able to respond to incremental stimuli presented on background fields so intense
      that 90% or more of the available rhodopsin is bleached during the exposure.
      These and other findings raise some doubts as to whether the skate has, in fact,
      an all-rod retina. In this paper, we present a body of evidence--based on the
      results of photochemical, anatomical, and electrophysiological studies--to
      support the view that only a single class of photoreceptor subserves vision in
      the skate retina. In addition, recent findings will be described that: a)
      demonstrate how the visual cells transform from sluggishly responding rods to
      brisk, cone-like elements, and b) may provide some insight into the functional
      significance of this unusual adaptive property.

PMID- 1982496
TI  - On the duplex nature of the skate retina.
AB  - The skate retina contains only one type of photoreceptor which has rod-like
      properties in the dark-adapted state. In the presence of background illumination,
      the receptors take on cone-like properties, i.e., their photoresponses become
      much faster, are less sensitive to light, and can be elicited in the presence of
      very bright backgrounds. Although the transformation is an extremely slow
      process, the skate retina performs like that of animals with mixed, rod-cone
      retinae. In this report we examine some postreceptoral features which may relate
      to this remarkable behavior. We show, for example, that the skate photoreceptor
      terminals make two kinds of junctions (ribbon synapses and basal junctions) that
      appear analogous to the two kinds of synaptic contacts made by cone terminals in
      other species. Furthermore, two types of horizontal cells are seen in the skate
      retina. Although the light-evoked responses of these horizontal cells are
      similar, there are differences in their current profiles recorded under voltage
      clamp, and in the nature of their dendritic processes. We have also observed
      several unusual postreceptoral structural features that may have some bearing on
      the response properties of the skate retina. In addition, a comparison of the
      adaptive properties of the receptor potential with those of intraretinal
      responses (b-wave, PNR) reveals differences that suggest strongly the presence of
      a network adaptive mechanism originating within the proximal retina. The network
      mechanism appears to be controlled to a large extent by the extracellular
      concentration of potassium [K+]0; i.e., changes in [K+]0 affect significantly the
      sensitivities of the b-wave and PBR, but have little effect on responses arising
      in the distal retina.

PMID- 1982497
TI  - Adaptations of visual pigments to the photic environment of the deep sea.
AB  - This is a summary of studies that bear on the problems of the adaptation of
      visual pigments to the photic environment of the deep sea. The results suggest
      that the spectral absorption of these retinal pigments is shifted toward the blue
      in order to match the dim, blue-green downwelling light and/or the
      bioluminescence of organisms that are critical to the life of the species.
      Through such a spectral match, greater visual sensitivity is achieved for life in
      the special photic condition of their habitat. This adaptation has been found for
      chimaerid fishes, for elasmobranchs, for teleosts, for mammals, and for certain
      crustaceans and cephalopods. The most convincing evidence for such an adaptive
      match has been found in teleosts that have red-emitting photophores. In these
      fishes a photopigment with absorbance shifted toward the red has been found by
      extraction and microspectrophotometry. A few exceptions to this idea of an
      adaptive match have appeared in the literature, the cone pigments, especially,
      being examples of such offset pigments. The malacosteid fishes have been shown to
      have a red-shifted retinal pigment with 11-cis-3-dehydroretinal as the
      chromophore and some invertebrates have also adopted this molecule to adjust the
      spectral absorption to the photic environment or to the bioluminescence. These
      studies are beginning to reveal that visual biochemistry is basically the same in
      vertebrates and invertebrates and that the visual pigment protein arose early in
      phylogeny and has been retained, with appropraite modifications, to the present.

PMID- 1982498
TI  - Rod and cone pigments of the Atlantic guitarfish, Rhinobatos lentiginosus Garman.
AB  - Using both extraction- and micro-spectrophotometric (MSP) methods the visual
      pigment(s) from the rods and cones of the Atlantic guitarfish, Rhinobatos
      lentiginosus, were shown to be spectrally similar, if not identical (lambda max =
      498-499 nm). Color vision, therefore, is unlikely unless mediated via colored oil
      droplets in the inner segments. The identical lambda max for the rod and cone
      pigments suggest that vision in both dim and bright light may correlate with the
      underwater spectrum over the depths and the times of day that guitarfish are
      active. The primary advantage of the blue-green sensitive visual pigments, we
      suggest, is to enhance the contrast of targets silhouetted against the background
      spacelight.

PMID- 1982499
TI  - Visual pathways in elasmobranchs: organization and phylogenetic implications.
AB  - Although earlier experimental studies of the visual system in elasmobranch fishes
      suggested that these fishes possess fewer primary retino-recipient nuclei than
      other gnathostome vertebrates, recent studies utilizing more sensitive tracing
      methods indicate that most elasmobranch species possess ten primary retinofugal
      targets in addition to the optic tectum. Furthermore, many species appear to
      exhibit bilateral retinal projections to these nuclei. Similarly, initial claims
      that the organization of the visual thalamus of elasmobranchs is more primitive
      than that of most other gnathostomes--in that elasmobranchs possess only a single
      thalamic nucleus that receives both retinal and tectal inputs and that only a
      single thalamo-telencephalic projection exists to the telencephalon--have been
      refuted. Many, if not all, elasmobranchs possess a rostrally located dorsal
      thalamic nucleus (anterior thalamic nucleus), that receives retinal and tectal
      inputs and projects bilaterally to the dorsal and medial pallium, and a more
      caudally and dorsally located thalamic nucleus, the dorsal posterior thalamic
      nucleus, that receives bilateral tectal input and projects to the ventrolateral
      periventricular area and/or dorsal pallium of the telencephalon. Thus the
      thalamic organization of elasmobranch fishes is similar to that of other
      gnathostomes.

PMID- 1982500
TI  - Synergistic T-T cell interaction present in alloreactivity: determination of 'MLR
      helper' T cell subsets.
AB  - CD4 and CD8 T cell subsets involved in primary allo-MLR responses were re
      evaluated in the present study. The slope analysis of B6 allo-MLR responses to
      MHC class I-disparate bm1 and class II-disparate bm12 revealed the presence of a
      T-T cell interaction between CD4 and CD8 T cell subsets. The allo-MLR response of
      B6 CD4 T cells to bm12 was completely blocked by anti-L3T4, indicating that the
      function of CD4 T cells is required for allo-MLR responses to bm12. It was
      further demonstrated that the function of CD8 T cells in class II-disparate allo
      MLR is to augment the proliferative response of CD4 T cells. On the other hand,
      CD8 T cells primarily responded to class I-disparate allo-MLR, and CD4 T cells
      function to augment the proliferative response of CD8 T cells. It was further
      indicated that CD4 and CD8 T cells recognize both class I and class II MHC. The
      CD4 T cell recognition of allo-class I and CD8 T cell recognition of allo-class
      II induces insufficient signals for proliferation of these T cells. Thus, the
      class I-reactive CD4 and class II-reactive CD8 T cell subsets function as helper
      cells ('MLR helper' T cells) for proliferating T cells in MLR responses.

PMID- 1982501
TI  - Lymphocyte leukocyte function-associated antigen 1 interacting with target cell
      intercellular adhesion molecule 1 co-activates cytolysis triggered via CD16 or
      the receptor involved in major histocompatibility antigen-unrestricted lysis.
AB  - The binding of leukocyte function-associated antigen 1 (LFA-1) (CD11a/CD18) to
      its natural target ligand, intercellular adhesion molecule 1 (ICAM-1) (CD54), is
      an important step in lymphocyte adhesion to cells and its subsequent activation.
      We studied whether LFA-1-ICAM-1 interactions affect tumor cell susceptibility to
      MHC-unrestricted lysis by TCR-CD3-CD16+ natural killer (NK) and TCR gamma delta +
      CD3+ CD16+/- lymphocytes. Moreover, tumor target cell susceptibility to anti-CD16
      mAb-triggered lysis by TCR- NK cells was investigated. Therefore, ICAM-1+ or ICAM
      1- tumor cell lines were used as target cells. Two melanoma-derived cell lines
      expressing little or no ICAM-1 were relatively resistant to MHC-unrestricted
      lysis as well as anti-CD16 mAb-triggered lysis by fresh or cloned TCR- NK cells.
      The ICAM-1- melanoma cell line was also relatively resistant to MHC-unrestricted
      lysis by TCR gamma delta + clones. Tumor necrosis factor (TNF) induced ICAM-1
      expression on ICAM-1- tumor cells, and simultaneously increased target cell
      susceptibility to MHC-unrestricted as well as to anti-CD16 mAb-triggered lysis.
      This enhanced level of lysis was inhibited by anti-ICAM-1 mAb. Our data
      demonstrate that LFA-1-ICAM-1 interactions increase MHC-unrestricted or CD16
      mediated cytolysis of tumor cells. Anti-CD18 interactions increase MHC
      unrestricted or CD16-mediated cytolysis of tumor cells. Anti-CD18 (LFA-1 beta)
      mAb inhibited MHC-unrestricted lysis of ICAM-1+ and ICAM-1- tumor cells.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1982502
TI  - AIDS in the nineties: from science to policy. Sixth International Conference on
      AIDS. San Francisco, June 20-24, 1990.

PMID- 1982503
TI  - Implications for the San Francisco model of care.

PMID- 1982504
TI  - Natural history of HIV and AIDS.

PMID- 1982505
TI  - Clinical aspects of HIV and AIDS.
AB  - The main messages from the Conference this year were that our management of
      opportunistic infections is improving with increasing therapeutic options
      available and better guidelines as to when to start treatment and prophylaxis.
      Since the first cases of the epidemic were reported in 1981 new drugs have been
      licensed, e.g. ganciclovir, fluxconazole and inhaled pentamidine. These have been
      developed, stimulated by the need for new agents to treat the increasing number
      of unusual infections. While the range of infections may not now be increasing so
      fast, the search for more effective, less toxic, agents continues.

PMID- 1982506
TI  - AIDS in the Nineties: from science to policy. Advances in clinical management.

PMID- 1982507
TI  - Health care workers and HIV/AIDS.

PMID- 1982508
TI  - HIV/AIDS in Africa.

PMID- 1982509
TI  - Psychiatric disorders associated with HIV disease.

PMID- 1982510
TI  - The psychological impact of HIV/AIDS.

PMID- 1982511
TI  - Review of neuropsychological studies of HIV infection.

PMID- 1982512
TI  - HIV/AIDS and sexual behaviour.

PMID- 1982513
TI  - AIDS in the Nineties: from science to policy. Drug users--epidemiology.

PMID- 1982514
TI  - AIDS in the Nineties: from science to policy. Drug user interventions.

PMID- 1982515
TI  - The family and HIV/AIDS.

PMID- 1982516
TI  - Haemophilia and HIV/AIDS.

PMID- 1982517
TI  - Using mass media for HIV/AIDS prevention.

PMID- 1982518
TI  - AIDS in the Nineties: from science to policy. Care in the community and by the
      community.
AB  - As the numbers of people with HIV infection increase the favoured option for care
      in the future is to increase community and home care. Without doubt also the
      statutory services have recognized the need to make prevention, educational and
      care services sensitive and appropriate to the client group they aim to serve and
      many unconventional systems are being put into place in order to do this. The
      reality of community care is so often care by the family and volunteers and there
      has to be some attempt to support informal carers materially and emotionally.
      Without the work of these groups it would be impossible for governmental or
      formal agencies to provide the necessary degree of quality of care. It would seem
      that a combination of pressure from the 'communities' affected by HIV/AIDS and
      flexibility in providing care by statutory and voluntary groups has made it
      possible to provide different schemes of community care or at least made suitable
      service delivery happen more quickly and more appropriately than might otherwise
      have been the case. There was some feeling at the conference that it would be
      comforting to think that some of these innovations, hard won for HIV/AIDS, could
      be replicated for groups of patients in the community who may not have such a
      vocal advocacy group to back them.

PMID- 1982520
TI  - Children and young adults with sex chromosome aneuploidy-- follow-up, clinical
      and molecular studies. Minaki, Ontario, Canada, June 7-10, 1989.

PMID- 1982519
TI  - HIV/AIDS management in Africa--new directions from the San Francisco Conference.

PMID- 1982521
TI  - The parental origin of the missing or additional chromosome in 45,X and 47,XXX
      females.
AB  - We used X-linked DNA polymorphisms to study the parental origin of the missing or
      additional X chromosome in conceptuses with 45,X or 47,XXX chromosome
      constitutions. Fifty-three (80.3%) of 66 cases of sex chromosome monosomy had a
      maternal X, demonstrating that paternal sex chromosome loss is the most common
      error leading to this condition. In contrast, 29 (93.5%) of 31 47,XXX cases
      resulted from maternal nondisjunction. In studies of parental age, we detected no
      obvious parental age effect for sex chromosome monosomy. For the 47,XXXs, there
      was an apparent association between increasing maternal age and errors at
      maternal meiosis I, but not maternal meiosis II. In other analyses, we detected
      no obvious effect of parental origin on the phenotype of either 45,X or 47,XXX
      conceptuses, at least as measured by comparing the ratio of paternal:maternal
      errors among different ascertainment categories.

PMID- 1982522
TI  - [The effect of cofactors on microsomal S-oxygenation of oxyprothepine].
AB  - Oxyprothepine in the medium of the microsomal fraction of the rat liver is
      biotransformed to the corresponding metabolites originating by oxidation of both
      sulfur atoms. The formation of S-oxygenation products is bound to the presence of
      NADPH, with a marked synergism with NADH. Induction with phenobarbital increases
      the formation of the individual metabolites.

PMID- 1982523
TI  - Glutamate toxicity in immature cortical neurons precedes development of glutamate
      receptor currents.
AB  - Cationic fluxes resulting from glutamate receptor activity have recently been
      implicated in neurotoxicity. Immature cortical neurons are insensitive to the
      toxic effects of glutamate receptor stimulation. However, these neurons are
      killed by glutamate via a non-receptor-mediated mechanism thought to stem from
      glutamate's ability to inhibit cystine uptake. To examine the basis for their
      resistance to receptor-mediated toxicity, we have studied the development of
      glutamate receptor-mediated inward currents in cortical neurons in culture using
      the whole-cell voltage-clamp technique. We report that in immature cortical
      neurons (prepared from day-17 fetal brain and cultured for 1-3 days), N-methyl-D
      aspartate, quisqualate, and glutamate are able to evoke only very small inward
      currents in a low percentage of neurons. After 7 days of culture, greater than
      80% of neurons examined exhibited currents activated by these glutamate receptor
      agonists. Although most neurons expressed glutamate agonist-evoked currents after
      7 days in culture, the amplitude of these currents was less than 10% of that
      observed after 15 days in culture. In contrast to currents activated by glutamate
      receptor agonists, those activated by gamma-aminobutyric acid reached maximal
      levels after only 2 days of culture. These results indicate that the delayed
      development of glutamate receptor-mediated currents accounts for the resistance
      of immature cortical neurons to glutamate receptor-mediated toxicity.

PMID- 1982524
TI  - Somatostatin mRNA and molecular forms during development of the rat retina.
AB  - The developmental control of rat retinal somatostatin (SS) expression was
      determined by Northern blot hybridization. The amount of SS transcript is higher
      than adult levels at embryonic day 16 and declines during late prenatal
      development. This pattern parallels the developmental expression of somatostatin
      immunoreactivity. The expression of somatostatin-immunoreactive peptide products
      using gel filtration chromatography was determined over the same period. Three
      molecular weight forms occur during development: a high m.wt. product and two
      smaller peptides which migrate with somatostatin-28 (SS28) and somatostatin-14
      (SS14). SS14 is the peptide that predominates at all developmental time points,
      and is the only form detectable in the adult retina. The transient prenatal
      increase of somatostatin message and peptide suggests a role for this peptide in
      the developing retina.

PMID- 1982525
TI  - Somatostatin gene expression in the developing monkey frontal and cerebellar
      cortices.
AB  - Somatostatin (SRIF) mRNA was determined in the developing monkey frontal and
      cerebellar cortices by the dot blot and the northern blot analyses at embryonic
      day 120 (E120), embryonic day 140 (E140), newborn stage (Nb), postnatal day 60
      (P60) and adult stage (Ad.) At E120, at which time the migration of the cortical
      neurons had already been completed, SRIF mRNA was detectable with 50% of the
      maximal value at E140 in the cerebral frontal cortex (von Bonin and Bailey's area
      FD). After E140, the level of mRNA gradually declined to the adult level by P60
      with 25% of the maximal value. In the cerebellum, SRIF mRNA was highly expressed
      at E120. The level decreased to 18% of the maximum at E140. Between the newborn
      and adult stages, there existed no positive signal of the mRNA. In contrast, both
      fetal and adult liver tissues contained no amounts of SRIF mRNA. We discussed the
      physiological meanings of the enhanced SRIF gene expression in the developing
      monkey cerebral and cerebellar cortices.

PMID- 1982526
TI  - Development and regulation of excitatory amino acid receptors involved in the
      release of arachidonic acid in cultured hippocampal neural cells.
AB  - Release of [3H]arachidonic acid mediated by excitatory amino acid (EAA) receptors
      was investigated from prelabelled primary cultures of hippocampal neurons and
      astroglial cells. Treatment with N-methyl-D-aspartate (NMDA), quisqualate (QA)
      and kainate resulted in age- and dose-dependent stimulation of [3H]arachidonic
      acid release. During development, the maximum response for NMDA was observed
      relatively earlier (at 7 days) than those for QA and kainate (at 14 days) in the
      hippocampal neuronal cultures. The half maximal effects were obtained at about 15
      microM NMDA at all ages studied and about 0.5 microM QA at 14 and 20 days. At
      optimum concentrations NMDA- and QA-induced releases were additive. Unlike with
      neurons, treatment with all the 3 EAA receptor agonists, NMDA, QA and kainate,
      had no significant effect on [3H]arachidonate release in hippocampal astroglial
      cells. In cultured 14-day-old neurons, the increases in NMDA- and QA-mediated
      [3H]arachidonic acid release were completely blocked by the NMDA receptor
      antagonist, 2-amino-5-phosphonovaleric acid, and the ionotropic QA receptor
      antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione, respectively. But the iontropic
      QA receptor agonist alpha-amino-3-hydroxy-5-methyl-isoxazole-4- propionic acid
      (AMPA) had no significant effect on [3H]arachidonate release, indicating that
      interaction between ionotropic QA and metabolotropic QA receptors may be
      essential for optimal QA-mediated arachidonic acid release. At physiological
      concentrations of Mg2+ (1.2 mM), AMPA was found to potentiate NMDA-induced
      release of [3H]arachidonic acid; the effect appeared to be related to a removal
      of Mg2+ blockade mediated by mild depolarisation.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1982528
TI  - [The detection of intergenomic restriction fragment length polymorphism in the
      region of the untranscribed spacer of the ribosomal repeat in cattle].

PMID- 1982527
TI  - Functional maturation of somatostatin neurons and somatostatin receptors during
      development of mouse hypothalamus in vivo and in vitro.
AB  - Ontogenesis of somatostatin (SRIF) neurons and receptors was studied in fetal
      hypothalamic cell cultures kept in serum-free medium, and compared to the in vivo
      developmental pattern. Initial rise in neuronal content of SRIF occurred later in
      vitro than in vivo. In vitro, K(+)-induced SRIF release was only present after
      synaptogenesis. SRIF binding sites were measurable as early as 1 day after birth
      and at an equivalent time in culture, after 6 days in vitro (DIV); their affinity
      was in the nanomolar range. In cultured cells, binding reached a maximum at two
      weeks in vitro and decreased sharply thereafter as a consequence of binding site
      occupancy by the endogenous ligand. Indeed, pretreatment with cysteamine
      decreased SRIF concentration in the neuronal cultures and twice as many binding
      sites as in control cultures of 21 DIV were measured. Competition kinetics using
      unlabelled SMS 201-995 to displace [125I]SRIF revealed two distinct binding sites
      in the neuronal preparations (IC50 = 11 +/- 3 pM and 4.5 +/- 0.8 nM). In
      contrast, only the lower affinity site was present on glial cell preparations
      (1.7 +/- 0.4 nM). SRIF inhibited adenylate cyclase activity in glia and neurons,
      and the onset of SRIF coupling to the second messenger occurred earlier in vitro
      than in vivo. Pertussis toxin pretreatment was equally effective in neuronal and
      glial cell preparations to decrease SRIF binding and to inhibit adenylate cyclase
      activity.

PMID- 1982529
TI  - Changes in the allelic methylation patterns of c-H-ras-1, insulin and
      retinoblastoma genes in human development.
AB  - The methylation status of the c-H-ras-1, insulin and retinoblastoma genes was
      determined in human sperm, hydatidiform mole, fetal tissues, adult lymphocytes
      and adult kidney. Individual alleles of c-H-ras-1 and insulin were
      distinguishable due to presence of endogenous variable number of tandem repeat
      (VNTR) polymorphisms. Both alleles of the latter two genes were extensively
      methylated in sperm compared to the other tissues. Several sites within these
      genes were less methylated in fetal tissues and the two alleles were
      differentially methylated in some cases. The retinoblastoma gene was highly
      methylated in all tissues examined, with the exception of a single site that was
      under-methylated in sperm only. The sperm-specific methylation patterns in all
      three genes could represent imprinting of the parental chromosomes. Since 5
      methylcytosine is inherently mutagenic, it is possible that methylation
      imprinting could alter the susceptibilities of human genes to point mutations.

PMID- 1982530
TI  - [The assessment of the work of the medical personnel at a feldsher-midwife
      center].

PMID- 1982532
TI  - International Symposium on Reverse Cholesterol Transport. Report on a meeting.
AB  - The purpose of this symposium was to provide a forum for the reporting of recent
      findings and the exchange of ideas concerning reverse cholesterol transport, an
      area of intense interest and some controversy. Data from epidemiological studies
      have consistently shown that elevated levels of high density lipoproteins (HDL)
      are an index of increased protection against coronary heart disease. However, the
      mechanism whereby HDL is involved in the prevention and/or reversal of
      atherosclerosis is unknown. According to one of the hypotheses, HDL acts as the
      primary acceptor of unesterified cholesterol from cells and functions jointly
      with the enzyme lecithin:cholesterol acyltransferase (LCAT) and the cholesteryl
      ester transfer protein (CETP) to facilitate the movement of cholesterol from
      peripheral tissues to the plasma and ultimately to the liver. Although this
      mechanism as originally proposed by Glomset is an essential physiological
      mechanism, the clinical significance of this hypothesis remains unsubstantiated.
      Key elements of knowledge are lacking that would allow the linking of cholesterol
      efflux from cells and tissues with specific events in HDL metabolism,
      particularly those that are relevant to the prevention and/or reversal of
      atherosclerosis. Because of the intricate nature of the interaction between the
      components of reverse cholesterol transport, a conference involving the leading
      investigators of the field, where extensive discussion of the findings and ideas
      is allowed, appeared highly desirable. Indeed, from the distance of nearly 4
      months, feedback from the participants indicates that the meeting was highly
      successful and the organizers feel that all the projected goals of the symposium
      were accomplished.

PMID- 1982531
TI  - Peptide opioids and morphine effects on inflammatory process.
AB  - Morphine was found to inhibit human granulocyte aggregation and ATP, thromboxane
      B2 (TxB2), and leukotriene B4 (LTB4) secretion during cell aggregation. None of
      the opioid peptides tested [(D-Ala2, D-Leu5)-enkephalin (DADL), (D-Ala2, N-Me
      Phe4, Gly-ol5)-enkephalin (DAGO) or dynorphin 1-9 (Dyn 1-9)] was capable of
      mimicking morphine effects, while Dyn 1-9 per se induced TxB2 and LTB4 secretion
      from granulocytes. Morphine inhibition of both cell aggregation and ATP, but not
      of arachidonic acid metabolism product secretion, was prevented by naloxone. The
      naloxone-sensitive impairment by morphine of CD11b-CD18 complex surface
      expression observed could play a role in opioid inhibition of granulocyte
      activation.

PMID- 1982533
TI  - Protective effect of pentoxifylline on phorbol myristate acetate-induced acute
      lung injury in rats.
AB  - The pathogenesis of adult respiratory distress syndrome (ARDS) is not clear, and
      its therapy is still a problem. Pentoxifylline, a methylxanthine derivative, can
      inhibit phosphodiesterase activity and thus increase the intracellular cAMP.
      There are also some hypotheses that pentoxifylline can attenuate pulmonary edema.
      In order to evaluate the protective effect of pentoxifylline in acute lung
      injury, we set up an isolated lung perfusion model in rats and induced
      experimental acute lung injury similar to ARDS by intravenously infused phorbol
      myristate acetate (PMA) 7.5 micrograms/300 g body weight. Four groups of
      experimental rats were studied: group 1, normal control group, neither PMA nor
      pentoxifylline was used in 6 rats; group 2 (acute lung injury group), only PMA
      was infused in 8 rats; group 3 (protective group), pentoxifylline 100 mg/300 g
      body weight was given intravenously before PMA infusion in 6 rats; group 4, only
      pentoxifylline was given in 6 rats. Pulmonary arterial pressure (PAP) as well as
      lung weight changes were recorded before and 5, 10, 15, 20 and 25 minutes after
      drug injection. Bronchial lavage fluids were then measured for albumin
      concentration. We found that PAP was strikingly increased in group 2 (54.0 +/-
      8.8 mmHg), but the increase was significantly reduced in group 3 (29.8 +/- 5.8
      mmHg, p less than 0.001). Similarly, the lung weight gain was markedly increased
      in group 2 (4.69 +/- 1.28 g), but was significantly attenuated in group 3 (1.25
      +/- 1.60 g, p less than 0.001). There was no apparent change in PAP and lung
      weight gain throughout the entire procedure in groups 1 and 4.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1982534
TI  - Maximal expiratory flow and volume in Chinese aged 60 years and over.
AB  - To obtain more accurate information about pulmonary function among elderly
      Chinese, we examined spirometry and maximal expiratory flow-volume curves in 180
      healthy nonsmoking subjects (102 women, 78 men) aged 60 years and over in Taiwan.
      Significant (p less than 0.05) age-related negative correlations were noted in
      forced vital capacity (FVC), mean forced expiratory flow between 25% and 75% of
      FVC (FEF25-75%) and maximal flow at 50% of FVC (Vmax50%) in both sexes. Forced
      expiratory volume in one second (FEV1)/FVC and maximal flow at 25% of FVC
      (Vmax25%) were negatively correlated with age in the men. Height was more
      positively correlated with the lung volume of FVC and FEV1 than with the flow
      rate of FEF25-75%, Vmax50% and Vmax25%. These spirometric values were lower in
      elderly Chinese than in elderly Caucasians even after adjustment for height and
      age. When the data were compared to the current prediction formulae used in our
      laboratory, which were mainly derived from healthy subjects younger than 60 years
      of age, FVC appeared well predicted. FEV1 and FEV1/FVC were slightly lower than
      the predicted value. On the contrary, Vmax50% and Vmax25% were much lower than
      the predicted value. This suggests that previous studies may have overestimated
      the flow rates, which may result in misinterpretation of small airways
      obstruction on the elderly. Regression equation were derived for predicting
      ventilatory parameters from elderly Chinese of both sexes. The multiple
      correlation coefficients (r) of flow rates with age and height were smaller than
      those reported in younger people. The standard error of estimate of the mean was
      large in FEF25-75%, Vmax50% and Vmax25% (30-37%).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1982535
TI  - Klebsiella pneumoniae bacteremia: analysis of 100 episodes.
AB  - In 1985, 100 episodes of klebsiella pneumoniae bacteremia in 98 patients were
      treated at the Veterans General Hospital--Taipei. The disease was community
      acquired in 58% and nosocomially acquired in 42%; unimicrobial in 86% and part of
      a polymicrobial bacteremia in 14%. Medical records of 90 episodes were available
      and were analyzed. Portals of entry, in decreasing order of frequency, were
      hepatobiliary (24%), respiratory (20%), and urinary tract (19%). Diabetes
      mellitus, which was found in 25 (28%) patients, was the most common underlying
      disease, followed by malignancies in 13 (14%), biliary tract abnormalities in 9
      (10%), and cirrhosis of the liver in 8 (9%). The most frequent clinical findings
      were fever (89%) and leukocytosis (60%), followed by thrombocytopenia (27%),
      jaundice secondary to bacteremia (22%) and shock (21%). The course of one (1%)
      patient, who was diabetic and had a liver abscess, was complicated by metastatic
      septic endophthalmitis and meningitis. Overall case fatality was 46%. Poor
      prognostic factors included inappropriate antibiotic therapy, respiratory tract
      as a portal of entry and the presence of shock. Cephalosporins and
      aminoglycosides were the most active antibiotics. The use of one or more
      antibiotics, which included at least one cephalosporin, with in vitro activity
      against the corresponding isolate, with adequate dosage and an appropriate route
      of administration significantly reduced deaths directly attributed to K.
      pneumoniae septicemia, 32% (18/57), compared with 88% (21/24) in patients who
      were not treated appropriately (p less than 0.001). Combination therapy with a
      cephalosporin and aminoglycoside in conjunction with surgery in selected cases is
      the treatment of choice for K. pneumoniae bacteremia.

PMID- 1982536
TI  - Legg-Calve-Perthes disease: clinical analysis of 57 cases.
AB  - The rarity of the Legg-Calve-Perthes disease (LCPD) in Chinese children in Hong
      Kong has been reported. However, this hip disorder is not uncommon among children
      in Taiwan between the ages of 3 and 9. Fifty-seven patients with LCPD were
      observed during a 4-year period. Of these, 47 hips in 43 patients were followed
      up through a significant course of the disease, with an average period of 38.8
      months. The mean age at onset of symptoms was 6.6 years for boys and 7.1 years
      for girls. Over half of the patients (67%) were older than 6 years of age at
      onset of the disease. The male: female ratio was 5:1, and the incidence of
      bilateral involvement was 10%. The majority (85%) belonged to Catterall's group 3
      or 4. The skeletal maturity of 17 (68%) these children was delayed an average of
      31.8 months. Fifty-three percent of the patients were from families of low
      socioeconomic status. Delay in diagnosis and presentation with painless limp and
      stiffness were common. Orthotic management was employed in 15 hips. Surgical
      containment, either by varus-rotation femoral osteotomy or innominate osteotomy,
      was achieved in 16 hips. The remaining 16 hips received no treatment. The overall
      results showed an increase in improvement from 19% to 47% after active treatment
      of the disease. The chance of satisfactory treatment was reduced considerably
      when the disease started after the age of 6 years, this was especially obvious in
      untreated hips. No significant differenced in the healing time between the
      nonsurgical group and the surgical group was observed.

PMID- 1982537
TI  - Spinal deformities among children under 10 years old: a clinical analysis of 41
      cases.
AB  - In order to investigate the number, types, severity and the various treatments of
      spinal deformity among children under 10 years old, a retrospective survey of
      registered patients in the scoliosis clinic at the National Taiwan University
      Hospital was performed. Between August 1982 and December 1988, there were 41
      children who had scoliosis with a Cobb angle larger than 10 degrees and the onset
      was before 10 years of age. This number accounted for 3.8% of all scoliotic
      patients during the same time period. Of these children, 19 had idiopathic
      scoliosis (46.3%), 7 with infantile and 12 with juvenile; the other 19 were due
      to congenital, and the remaining 3 were postradiation, a resection of Wilms'
      tumor in 2 and neuroblastoma in 1. In the congenital group, hemivertebra (13
      patients) outnumbered other causes. Twenty three patients (56%) underwent
      surgical correction, the rest were either under regular observation (9 patients),
      bracing (7 patients) or electrical stimulation (2 patients). The average
      preoperative Cobb angle in the operated groups was much larger, being 67.6
      degrees in the infantile; 52.4 degrees in the juvenile; 57 degrees in the
      congenital; and 62 degrees in the postradiation. For those without an operation,
      the angles were smaller than 30 degrees. The indications for surgery were that
      the curvature was in progression, which could not be controlled by conservative
      means, or that in some congenital cases, the curve had the potential tendency to
      exacerbate. From the present study, the percentage of scoliosis under 10 years of
      age was far less than the adolescent group in our clinic.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1982538
TI  - Correlation between sonography and pathology in thyroid diseases.
AB  - Ultrasonography was performed on the thyroid glands of 47 patients with various
      thyroid diseases, in a fresh state, immediately following operation. The thyroid
      glands were then sectioned along the plane of the most significant sonographic
      changes. The pathologic changes of the sectioned plane were observed and compared
      with the sonographic changes. In nodular goiter, the sonographic changes were
      usually heterogeneous. The margin was either well-defined or ill-defined, and
      cystic changes might play a minor or major part in the thyroid nodules. In
      follicular adenoma, the changes were isoechoic in adenoma with embryonal type
      follicles and hyperechoic in adenoma with colloid type follicles. In adenoma of
      the oxyphilic cells, the echogenicity was somewhat greater in the hemorrhagic
      part compared to the area with oncocytic change only. In papillary carcinoma, the
      lesions usually manifested as well-limited, heterogeneous, hypoechoic nodules.
      Cystic degenerations were frequently noted. There were discrete particles
      corresponding to microcalcification in 4 out of 6 cases. In follicular carcinoma,
      the sonographic changes also showed well-limited nodules. However, the
      echogenicity was not decreased as much as in papillary carcinoma, and it could be
      either homogeneous and isoechoic, or hypoechoic. Relatively large particles with
      an acoustic sign, which corresponded to calcification, were noted in 2 out of 4
      cases. In medullary carcinoma, the lesion was well-limited and hypoechoic. The
      particles present in sonography corresponded to calcification in the amyloid. In
      Graves' disease, the main sonographic change was a diffusely homogeneous,
      isoechoic or hypoechoic lesion. Cystic change was rarely present. Dispersed
      particles were rarely present and corresponded to fibrosis in the thyroid
      tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1982539
TI  - Radionuclide transit studies for esophageal function before and after esophageal
      transection and devascularization.
AB  - Nonobstructive swallowing disturbance is a common complication following
      esophageal transection and devascularization to control bleeding from esophageal
      varices. From July 1983 to July 1984, 12 patients underwent both a radionuclide
      esophageal transit study (RETS) and a barium swallowing fluoroscopic study (BSFS)
      before and after surgery to evaluate esophageal function. Before surgery, 9 of
      the 12 patients had no swallowing disturbance and the RETS was normal in 8 cases,
      and the BSFS was normal in all cases. Three patients who received sclerotherapy
      on more than 3 occasions suffered from swallowing disturbances and both the RETS
      and BSFS detected their defective passage. The average distal 1/3 segmental and
      total esophagus transit times were 11.5 +/- 9.9 seconds and 13.0 +/- 10.6 seconds
      among symptom-free patients; and 24.8 +/- 11.8 seconds and 30.1 +/- 14.6 seconds
      among swallowing-disturbance patients. The time prolongation was significant (p
      less than 0.005). After surgery, 5 of 9 preoperative symptom-free patients
      suffered from swallowing disturbances for 10 days and then became symptom free.
      Their serial follow-up RETS and BSFS at 1 month, 3 months and 6 months all showed
      normal results. One preoperative symptom-free patient suffered from a mild
      swallowing disturbance for 2 months. However, only RETS, but not BSFS,
      demonstrated the prolonged proximal segmental esophageal transit time at 1 month
      postoperatively. The remaining 6 patients suffered from prominent swallowing
      disturbances and their initial postoperative RETS demonstrated prolonged
      defective transit or the presence of gastroesophageal (GE) reflux. All these
      events were confirmed by both tests.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1982540
TI  - Rapid and simple immunoassays for measurement of human chorionic gonadotropin
      using monoclonal antibodies.
AB  - Two monoclonal antibodies, designated Gab-35 and Gab-144, were used in
      competitive radioimmunoassay (RIA) and solid-phase sandwich enzyme immunoassay.
      By SDS-polyacrylamide gel electrophoresis and protein blot enzyme immunobinding
      assay, Gab-35 and Gab-144 were shown to react specifically to the alpha-subunit
      and beta-subunit of human chorionic gonadotropin (hCG), respectively. The
      immunoglobulin class and subclass of these two monoclonal antibodies were found
      to be IgG1 by the Ouchterlony double gel immunodiffusion test. The beta-subunit
      specific monoclonal antibody of Gab-144 was used in competitive RIA for
      determination of serum hCG in the range of 5-500 mIU/ml. The assay results
      correlated well with the monoclonal antibody-based RIA system and commercial RIA
      kits using polyclonal antisera. Moreover, the present competitive RIA system
      showed a shorter incubation time (1 hour 20 minutes) and a shorter total assay
      time (1 hour 40 minutes), as compared to those of the commercial RIA kit. A solid
      phase sandwich enzyme immunoassay was developed using a combination of the Gab-35
      antibody-coated microtiter plate and the beta-subunit specific antibody of Gab
      144 conjugated with horseradish peroxidase (HRP). The assay range was 20-200
      mIU/ml, and the incubation time was only 30 minutes. In addition, the solid-phase
      sandwich enzyme immunoassay developed in the present study could also be used as
      a qualitative hCG assay with a cutoff point of 50 mIU/ml as an early pregnancy
      test at or just a few days before the missed period.

PMID- 1982541
TI  - Subacute necrotizing encephalomyelopathy (Leigh's disease): report of a case.
AB  - A 5-month-old male infant was referred to us for evaluation of progressive
      hypotonia. He had growth retardation, feeding difficulty and general weakness.
      Brain sonography and computed tomography demonstrated symmetrical lesions in the
      caudate, lenticular nuclei, thalamus and hypothalamus, suggesting bilateral
      necrosis. Lactate and pyruvate levels in the blood and cerebral spinal fluid were
      persistently elevated. A biopsy of the quadriceps muscle showed increased
      subsarcolemmal mitochondrial enzyme activity on light microscopy. Electron
      microscopy of the muscle showed deformed and bizarre mitochondria. The patient
      eventually died at the age of 8 months. Autopsy showed bilateral necrotic foci in
      the caudate, lenticular nuclei, thalamus, hypothalamus, midbrain, and pons.
      Histopathologic findings included spongiform degeneration of the affected brain
      tissue. The characteristic clinical and pathological findings confirmed this case
      as subacute necrotizing encephalo-myelopathy of Leigh's type. To our knowledge,
      this is the first autopsy-proven case of Leigh's disease in Taiwan.

PMID- 1982542
TI  - Antenatal ultrasonographic diagnosis of hypotelorism.
AB  - Hypotelorism is one of the most important fetal anomalies, which deserves early
      antenatal detection and management. To date, only a few cases of antenatally
      diagnosed hypotelorism have been reported. In this series, we report a case of
      hypotelorism and microphthalmia diagnosed prenatally. A 30-year-old female, G1P0,
      was admitted to our hospital due to chronic bronchitis and a breech presentation
      of the fetus at 38 weeks of gestation. Routine ultrasound screening revealed
      hypotelorism. Associated anomalies detected by ultrasound were alobar
      holoprosencephaly, microcephaly, microphthalmia and oligohydramnios. After
      delivery, hypotelorism with holoprosencephaly was confirmed, which corresponded
      with the antenatal ultrasound findings. In conclusion, systemic routine
      ultrasound screening of fetal orbits is the best way to prenatally detect
      hypotelorism and microphthalmia.

PMID- 1982543
TI  - Congenital Letterer-Siwe disease with intrauterine fetal death: a case report and
      review of the literature.
AB  - Letterer-Siwe disease is a rare proliferative disorder of the Langerhans cells,
      usually encountered inpatients under the age of 3 years. We present an unusual
      case of intrauterine fetal death at the 28th gestational week associated with
      generalized papular skin eruptions and systemic histiocytic infiltrates
      characteristic of Letterer-Siwe disease. Histopathologic features of Langerhans
      cells were further confirmed by immunocytochemistry and electron microscopy. The
      events occurring in pregnancy which may be worth mentioning are: (1) routine
      chest P-A view X-ray exposure of the mother 2 days before LMP, (2) the mother was
      exposed to certain Chinese herbs, in particular, the 101 hair growth solution (A
      Chinese herb mixture used for alopecia; contents unknown) from assisting her
      husband in topical applications, and (3) the mother has worked in front of
      computer monitors 8 hours a day for 10 years.

PMID- 1982545
TI  - Inflammatory pseudotumor of the liver with occlusive endophlebitis: report of a
      case.
AB  - Inflammatory pseudotumor (IPT) of the liver is an extremely rare benign tumor.
      Only 12 cases have so far been reported in the English literature. The etiology
      and pathogenesis of IPT remain obscure. We herein present an additional case of
      IPT of the liver with occlusive endophlebitis in a 36-year-old female.
      Immunohistochemical studies demonstrated the polyclonal nature of the plasma
      cells in the tumor, including IgA, IgM, IgG, kappa and lambda. The inflammatory
      pseudotumor should be kept in mind in the differential diagnosis of hepatic space
      occupying malignant lesions.

PMID- 1982544
TI  - Giant hydronephrosis: report of 4 cases with review of the literature.
AB  - Giant hydronephrosis is uncommon. In 1939, Stirling defined it as the presence of
      more than 1,000 ml of fluid in the collecting system [1]. We herein report 4
      cases of giant hydronephrosis containing 1,900 ml, 3,400 ml, 2,100 ml and 3,200
      ml, respectively. Only 6 cases with a malignant tumor have been reported in the
      literature. Our second case with multiple foci of transitional cell carcinoma
      with squamous metaplasia is presented. This is the first report of this kind of
      pathological morphology with giant hydronephrosis. An erroneous diagnosis is
      often made in cases of giant hydronephrosis. For example, 3 of our 4 patients
      were first diagnosed as ovarian cyst, retroperitoneal hamartoma and hepatic cyst,
      respectively. We have found 523 cases reported in the literature. It is seen more
      often in males than in females (2.4:1) and more often on the left side than on
      the right side (1.8:1). The amount of fluid in the hydronephrotic sac is often
      between 1 and 2 liters. It is usually secondary to ureteropelvic junction
      obstruction, stones or congenital abnormality. Nephrectomy is often performed due
      to severe impairment of renal function. Acute renal failure and cardiopulmonary
      distress developed in our second case after the operation. The reason may be the
      sudden decompression of the huge hydronephrotic sac, which resulted in a change
      in the hemodynamic balance. Therefore, a two-stage procedure with slow
      decompression by percutaneous nephrostomy before the nephrectomy is preferred in
      the compromised patient.

PMID- 1982546
TI  - [Acute hemodynamic effects of upper airway obstruction in normal dogs].
AB  - Eight normal dogs were anesthetized to assess the effects of an upper airway
      obstruction (UAO) on arterial blood gases (ABG) and hemodynamic (HD) parameters.
      Each dog was fitted with an arterial line, a Swan-Ganz catheter and an
      endotracheal tube. The HD parameters including heart rate, systolic blood
      pressure, central venous pressure (CVP), cardiac index (CI), pulmonary capillary
      wedge pressure (PCWP), systemic vascular resistance index (SVRI), pulmonary
      vascular resistance index (PVRI), left ventricle stroke work index (LVSWI) and
      right ventricle stroke work index (RVSWI), were monitored. The baseline ABG and
      HD parameters were taken prior to endotracheal tube clamping, and then checked at
      0.3, 1.5, 3.0, 4.0 and 5.0 minutes. The clamp was subsequently removed to allow
      spontaneous breathing, and then another set of measurements were taken at 5, 15
      and 30 minutes, respectively. The above procedures were then repeated a second
      time. The results showed that UAO can produce the following: (1) decreases in the
      CI, PaO2 and pH; (2) increases in the mean systemic and pulmonary arterial
      pressure, PCWP, SVRI, PVRI, LVSWI, RVSWI, and PaCO2; (3) significant and acute
      changes in PaO2 and pH, with the most significant changes occurring within 90
      seconds after clamping and then reaching a plateau; and (4) repeated UAO
      increases in SVRI and PVRI. In conclusion, upper airway obstructions may possibly
      induce serious ABG and HD changes in humans, as it does in normal dogs.

PMID- 1982547
TI  - [Testicular morphological and biochemical changes after Fowler-Stephens
      orchiopexy in rats].
AB  - Fowler-Stephens orchiopexy is the most common method of treating high-positioned
      undescended testes. Its success rate has been reported to be as high as 50-70%
      based on palpation or in a few circumstances on biopsy. Although it is convenient
      to evaluate testicular function by palpation and/or biopsy, this method is very
      subjective and is not scientific enough. To determine testicular function more
      precisely and objectively, we performed the Fowler-Stephens orchiopexy on Sprague
      Dawley rats and observed the morphological and biochemical changes, including
      assays of LDH, SDH and the testosterone level. In our morphological study, with
      the use of Fowler-Stephens orchiopexy, only 17% (3/18) of the rat tests could be
      salvaged. The others revealed either necrosis or fibrosis. Testicular LDH,
      checked at the 4th postoperative week, revealed 0.62 +/- 0.04 U/mg which was
      statistically different (p less than 0.05) from that of the control group and the
      hemicastrated group (0.77 +/- 0.05 U/mg and 0.76 +/- 0.07 U/mg, respectively).
      The SDH obtained from the testes also revealed significant differences between
      the study group and the control and hemicastrated groups. Values obtained were
      2.67 +/- 0.15 mU/mg, 3.77 +/- 0.4 mU/mg and 3.77 +/- 0.33 mU/mg, respectively (p
      less than 0.05). Using electrophoresis, 3 out of 18 rats had typical X bands,
      which is the classical picture of a normal mature testis. In contrast, the others
      showed faint X bands at the 2nd postoperative week, which subsequently faded
      thereafter. During testicular ischemia, the Leydig cells are more resistant than
      the Sertoli cells and the germinal cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1982549
TI  - [Love--skill and knowledge].

PMID- 1982548
TI  - Effects of FRG-8701 on gastric acid secretion, gastric mucosal lesions by
      necrotizing agents and experimental gastric or duodenal ulcer in rats.
AB  - Effects of FRG-8701, a new histamine H2-receptor antagonist, on gastric acid
      secretion, necrotizing agents-induced gastric lesions and acute gastric or
      duodenal ulcer in rats were studied. In lumen-perfused rats, intravenous
      injection of FRG-8701 reduced gastric acid secretion, and its antisecretory
      effect was almost equipotent to that of famotidine but the duration of action was
      substantially longer. In pylorus-ligated rats, the antisecretory effect of
      intraduodenal FRG-8701 administration was about 7 times more potent than that of
      cimetidine. FRG-8701 effectively inhibited macroscopic gastric hemorrhagic
      lesions induced by various kinds of necrotizing agents. Intraperitoneal injection
      was effective in preventing the lesions as well as oral treatment. The oral ED50
      values for these lesions ranged from 1.1 to 9.4 mg/kg. On the other hand,
      famotidine failed to reduce these lesions, and the cytoprotective effect of
      cimetidine was observed only in high doses compared with the doses for
      antisecretory activity. In addition, the cytoprotective effect of FRG-8701 was
      not affected by the treatment of indomethacin or N-ethylmaleimide. FRG-8701
      showed antiulcer activity against stress and indomethacin gastric ulcer and
      mepirizole duodenal ulcer. Its antiulcer effect was 5-15 times more potent than
      that of cimetidine. These results indicate that FRG-8701 is a new antiulcer drug
      that exerts a potent cytoprotective effect in addition to its gastric
      antisecretory activity.

PMID- 1982550
TI  - [Modern medicinal agents used in rheumatoid arthritis].

PMID- 1982551
TI  - Adherence and pathogenesis of Salmonella enteritidis in mice.
AB  - Adherence of many pathogenic organisms to the host cells has been associated with
      the presence of fimbriae. The exact role of these organelles in the adherence and
      pathogenesis of Salmonella enteritidis is not well established. Utilizing
      hemagglutination tests, S. enteritidis was shown to possess type 1 and type 3
      fimbriae. Polyacrylamide gel electrophoresis of the isolated fimbriae showed that
      type 1 and 3 fimbriae of S. enteritidis had subunit M.r of 17 and 22 kDa,
      respectively. In vitro adherence assays suggested that S. enteritidis utilized
      type 1 fimbriae to adhere to human buccal and mouse small intestine epithelial
      cells. In addition, antibody produced against type 1 and type 3 fimbriae
      protected the mice from infection with a lethal dose of S. enteritidis. These
      results suggest that type 1 and possibly type 3 fimbriae are involved in the
      adherence and pathogenesis of S. enteritidis. The data further suggest that they
      may have a role in the adherence and pathogenesis of the other enteric organisms.

PMID- 1982552
TI  - Pili of an Aeromonas hydrophila strain as a possible colonization factor.
AB  - Aeromonas hydrophila Ae6 had 2 morphologically distinctive kinds of pili. One
      appeared rigid and straight with a diameter of 9 nm (R-pili). The other appeared
      wavy and flexible with a diameter of 7 nm (W-pili). W-pili were very few on the
      cell as compared with R-pili. In this study, W-pili were purified and
      characterized. The pili consisted of a subunit protein with a molecular weight of
      21 kDa as estimated by SDS-PAGE. There was no immunological cross-reaction
      between W-pili and other cellular components. The strain Ae6 and its purified W
      pili adhered to human and rabbit intestine and agglutinated human and rabbit
      erythrocytes. Organisms pretreated with the Fab fraction of anti-pilus antibody
      failed to adhere to the intestine. Pretreatment of intestine with purified W-pili
      blocked adherence of the organisms to the intestine. These results suggest that
      the W-pili are the colonization factor of A. hydrophila Ae6.

PMID- 1982553
TI  - Maternal cocaine addiction. II: An animal model for the study of brainstem
      mechanisms operative in sudden infant death syndrome.
AB  - Respiratory control abnormalities are mechanistic in Sudden Infant Death Syndrome
      (SIDS). In particular, arousal form sleep is an important component of
      respiratory regulation. Cocaine alters central neurotransmitter metabolism,
      particularly the monoamines. The locus coeruleus, the major Norepinephrine (NE)
      neuronal system, is involved in arousal from sleep related apnea and has
      extensive forebrain and brainstem projections. Thus, it is plausible that in
      utero cocaine exposure disrupts the normal maturation of transmitters and/or
      brain structures essential to sleep related respiratory regulation. Infants
      exposed to cocaine in utero may have an increased incidence of SIDS. We propose
      that cocaine use in pregnancy alters the normal maturation of centers and/or
      neurotransmitters involved in respiratory regulation thereby altering postnatal
      respiratory control. We hypothesize that the increased incidence of SIDS in
      cocaine exposed infants may be secondary to deficits in arousal. The study of
      prenatal brain development and of postnatal respiratory control in rabbit pups
      exposed to cocaine in utero will provide a useful model for the study of
      mechanisms operative in SIDS.

PMID- 1982554
TI  - Evidence for kinetoplast and nuclear DNA homogeneity in Trypanosoma evansi
      isolates.
AB  - The kinetoplast DNA minicircles from 13 stocks of trypanosomes designated as
      Trypanosoma evansi were digested with various restriction enzymes. We also
      examined the distribution of restriction site polymorphisms in the nuclear DNA of
      9 of these stocks, using 7 different variable surface glycoprotein (VSG) and non
      VSG probes. Restricted kinetoplast DNA (kDNA) fragments of some of these strains
      were cloned into M13 or PUC 18 vectors and sequenced. The restriction and
      sequence mapping showed that most of T. evansi isolates belonged to the A1 and A2
      types of Borst and to two new closely related types A3 and A4. A notable
      exception was RoTat 4/1 derived from a Sudanese stock which was found to display
      a characteristic brucei-like minicircle heterogeneity. The T. evansi minicircles
      analysed are not only homogeneous in sequence but also the region similar to the
      conserved region in Trypanosoma brucei and Trypanosoma equiperdum is flanked on
      its 5' end by a palindromic repeat of part of the conserved region. The highly
      conserved sequence GGGCGGT which appears to correspond to the initiation of
      synthesis of one of the Okazaki fragments contains an additional G and is located
      as in T. brucei and T. equiperdum about 73 bp 5' from the ORI. The nuclear DNA
      analysis confirms the kDNA study in that all the T. evansi stocks are members of
      a very homogeneous group in terms of sequence divergence. Moreover, our analysis
      also confirms that T. evansi is more closely related to the West African T. b.
      brucei and T. b. gambiense than to other African trypanosomes.

PMID- 1982555
TI  - Differential expression of a family of putative adenylate/guanylate cyclase genes
      in Trypanosoma brucei.
AB  - The expression site for the variant surface glycoprotein (VSG) gene of
      Trypanosoma brucei contains several genes of unknown function (ESAGs, for
      expression site-associated genes). Among these, ESAG 4 shows homology to
      eukaryotic adenylate/guanylate cyclase genes, in the region encoding the
      presumptive enzyme catalytic domain. This gene belongs to a family of related
      sequences, and hybridizes to the genomic DNA of other trypanosomatids, such as
      Trypanosoma congolense, Trypanosoma vivax and Trypanosoma mega. While ESAG 4 is
      transcribed only in bloodstream forms by a RNA polymerase resistant to alpha
      amanitin, at least three other members of this family are transcribed in both
      bloodstream and procyclic forms, by a RNA polymerase sensitive to the drug. These
      genes encode different putative transmembrane proteins showing high sequence
      conservation in the region corresponding to the adenylate/guanylate cyclase
      catalytic domain.

PMID- 1982556
TI  - Blockade of alpha 2-adrenoceptors increases opioid mu-receptor-mediated
      inhibition of the firing rate of rat locus coeruleus neurones.
AB  - In pontine slices of the rat brain, the frequency of spontaneous action
      potentials of locus coeruleus (LC) neurones was recorded extracellularly.
      Noradrenaline 0.1-100 mumol/l, UK 14,304 0.01-100 nmol/l, [Met5]-enkephalin 1
      10,000 nmol/l and [D-Ala2,D-Leu5]enkephalin 0.1-1,000 nmol/l, all depressed the
      firing rate. Rauwolscine 1 mumol/l antagonized the effects of both noradrenaline
      and UK 14,304, but potentiated the effects of [Met5]enkephalin and [D-Ala2, D
      Leu5]enkephalin. Idazoxan 1 mumol/l acted in a similar manner. Prazosin 1 mumol/l
      did not change the effects of either noradrenaline or [Met5]enkephalin. Naloxone
      0.1 mumol/l antagonized both [Met5]enkephalin and [D-Ala2, D-Leu5]enkephalin, but
      failed to alter the effects of either noradrenaline or UK 14,304. Rauwolscine,
      idazoxan and prazosin, all 1 mumol/l, as well as naloxone 0.1 mumol/l, did not
      influence the firing rate when given alone. Desipramine 1 mumol/l inhibited the
      discharge of action potentials in a rauwolscine-antagonizable manner.
      Noradrenaline 10 mumol/l produced the same depression of firing, both in the
      presence of noradrenaline 1 mumol/l and [Met5]enkephalin 0.03 mumol/l. Likewise,
      the effect of [Met5]enkephalin 0.3 mumol/l was the same, irrespective of whether
      it was added to a medium containing [Met5]enkephalin 0.03 mumol/l or
      noradrenaline 1 mumol/l. The spontaneous activity of LC neurones is inhibited by
      somatic alpha 2-adrenoceptors and opioid mu-receptors. We suggest that the two
      receptors interact with each other at a site located between themselves and not
      in the subsequent common signal transduction system.

PMID- 1982557
TI  - Effect of BHT 920 on monoaminergic neurons of the rat brain: an
      electrophysiological in vivo and in vitro study.
AB  - BHT 920 was originally described as a dopamine autoreceptor agonist. In this
      study, the effect of this compound on the firing rate of noradrenergic locus
      coeruleus, serotonergic dorsal raphe and dopaminergic ventral tegmental area
      neurons was examined both in the anaesthetized rat and in rat brain slices.
      Extracellular recordings were performed in cells whose identity was determined by
      electrophysiological, pharmacological and histological criteria. In vivo, BHT 920
      inhibited the firing of locus coeruleus neurons (ID50: 14.5 +/- 4.7
      micrograms/kg, mean +/- SEM) and ventral tegmental area neurons (ID50: 7 +/- 3
      micrograms/kg) at very low doses. As a comparison, the ID50 of clonidine on locus
      coeruleus cells was 5.5 +/- 0.6 microgram/kg and the ID50 of apomorphine on
      ventral tegmental area neurons was 13 +/- 3 micrograms/kg. BHT 920 also decreased
      the firing of dorsal raphe cells, but this effect was obtained at higher doses
      (ID50: 57 +/- 11 micrograms/kg). The in vitro study confirmed the results
      obtained in vivo. BHT 920 potently inhibited the firing of locus coeruleus cells
      (IC50: 71 +/- 28 nM) and was less potent than clonidine (IC50: 5.3 +/- 0.98 nM).
      The compound also inhibited the firing of ventral tegmental area neurons at very
      low concentrations (IC50: 21 +/- 3.3 nM), being more potent than apomorphine
      (IC50: 56 +/- 29 nM). BHT 920 only slightly decreased the firing rate of dorsal
      raphe neurons at 50 microM, showing that the drug has little direct effect on
      these cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1982558
TI  - Modulation of 5-hydroxytryptamine release by presynaptic inhibitory alpha 2
      adrenoceptors in the human cerebral cortex.
AB  - Slices and synaptosomes from human cerebral cortex (which had to be removed to
      reach deeply located tumours) and, for comparison, synaptosomes from guinea-pig
      and rat cerebral cortex were preincubated with [3H]5-hydroxytryptamine and
      superfused with physiological salt solution containing an inhibitor of 5
      hydroxytryptamine uptake. The effects of alpha-adrenoceptor agonists and
      antagonists on the electrically (slices) or potassium-evoked (synaptosomes)
      tritium overflow were studied. In human cerebral cortical slices, the
      electrically-evoked [3H] overflow was inhibited by noradrenaline (pIC25 value:
      6.35); the non-selective alpha-adrenoceptor antagonist phentolamine, at a
      concentration of 0.32 mumol/l, strongly antagonized the inhibitory effect of
      noradrenaline (apparent pA2 value: 8.19) but did not affect the evoked overflow
      by itself. In synaptosomes from humans, guinea-pigs and rats, noradrenaline also
      inhibited the K(+)-evoked [3H] overflow in a concentration dependent manner; the
      alpha 2-adrenoceptor clonidine (1 mumol/l), but not the alpha 1-adrenoceptor
      agonist methoxamine (1 mumol/l), mimicked the effects of noradrenaline; the
      effect of noradrenaline (0.3 mumol/l) was abolished by the alpha 2-adrenoceptor
      antagonist idazoxan (0.5 mumol/l), but not by the alpha 1-adrenoceptor antagonist
      prazosin (1 mumol/l). It is concluded that release-inhibiting adrenoceptors of
      the alpha 2-subtype exist on 5-hydroxytryptamine terminals innervating the
      cerebral cortex in human and guinea-pig brain.

PMID- 1982559
TI  - Adenosine modulation of non-adrenergic non-cholinergic neurotransmission in
      isolated guinea-pig atria.
AB  - Transmural stimulation of non-adrenergic, non-cholinergic sensory nerves in
      guinea-pig atria, isolated from reserpine-pretreated animals, in the presence of
      atropine and the beta-adrenoceptor-blocking drug CGP 20712A, induced a positive
      inotropic effect. Adenosine (0.1-10 microM) concentration-dependently reduced the
      cardiac response to transmural nerve stimulation, without modifying the response
      to exogenous calcitonin gene-related peptide; the inhibitory effect of adenosine
      was antagonized by 1 microM 8-phenyltheophylline. Moreover, the cardiac response
      to field stimulation was enhanced by 8-phenyltheophylline (0.1, 1 microM) and by
      adenosine deaminase (1 microgram/ml), but was reduced by dipyridamole (1 microM).
      These findings indicate the presence of inhibitory adenosine receptors on cardiac
      sensory nerves and suggest a modulatory effect of endogenous adenosine on cardiac
      non-adrenergic, non-cholinergic neurotransmission.

PMID- 1982560
TI  - Dopaminergic regulation of striatal cholinergic interneurons: an in vivo
      microdialysis study.
AB  - In vivo microdialysis was used to study the putative inhibitory effects of
      dopamine on cholinergic interneurons in the striatum of conscious rats. The
      dopamine receptor agonists apomorphine (0.3 and 3 mg/kg, s.c.) and (+/-)N-0437
      (1.4 mg/kg, s.c. decreased interstitial concentrations of acetylcholine while
      increasing those of choline. In contrast, the dopamine receptor antagonists
      haloperidol (0.1 and 1 mg/kg, i.p.) and (+/-)sulpiride (20 mg/kg, i.p.) enhanced
      striatal acetylcholine output but had little effect on choline. Previously, a
      lack of effect of these drugs on striatal acetylcholine was reported. The main
      methodological difference between these studies was that the calcium
      concentration of the microdialysis perfusion solution was 3.4 mM in the former
      study versus 1.2 mM in the present experiments. The results of this study
      reemphasize the importance of the calcium concentration in determining the
      effects of drugs on central neurotransmitter release, and confirm a role of
      dopamine in the regulation of striatal cholinergic interneurons.

PMID- 1982561
TI  - Peripheral vascular and neuronal effects of dopamine receptor agonists. A
      comparison with receptor binding studies in rat striatum.
AB  - A series of dopamine (DA)-receptor agonists was tested in vitro on vascular DA1-
      and neuronal DA2-receptors and the activity observed was compared to their
      ability to compete with [3H]-SCH23390 and [3H]-domperidone binding to rat
      striatal membranes. In rabbit splenic artery, where the presence of the DA1
      receptor is established, DA and related agonists produced a complete
      concentration-dependent relaxation of the thromboxane A2-mimetic U46619-induced
      tone in IBMX (3-isobutyl-1-methylxanthine) treated preparations. The DA
      vasorelaxant effect proved to be mediated by DA1-receptors, being inhibited by
      the selective DA1-receptor antagonist SCH23390. Fenoldopam proved to be the most
      potent agonist in the rabbit splenic artery consistent with the result obtained
      in the D1-receptor binding assay. Epinine was about 5 times more potent than DA
      and only 3 times less active than fenoldopam on DA1-receptors although the D1
      receptor binding study did not reveal major differences from DA. An opposite
      profile was observed with N,N-di-n-propyl dopamine (DPDA) showing a functional
      potency lower than that expected from the binding assay. In cat right atrium, DA
      and related agonists caused concentration-dependent inhibition of the tachycardia
      induced by electrical stimulation. The DA effects proved to be mediated by
      presynaptic DA2-receptor activation, being inhibited by the selective DA2
      receptor antagonist domperidone. The DA2-receptor agonist 6-(di-n-propylamino)
      5,6,7,8-tetrahydro-1,2-naphthalenediol (DP-5,6-ADTN) was the most potent compound
      both in the cat atrium and in the binding assay. Epinine was 2 times more potent
      than DA on DA2-receptors but it showed no differences in the D2-receptor binding
      assay.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1982563
TI  - Stability of somatostatin in total parenteral nutrition.
AB  - The stability of somatostatin, added to a total parenteral nutrition formula, in
      glass containers and in plastic ethylene vinyl acetate containers was
      investigated. The somatostatin concentration decreased immediately from 3
      micrograms/ml to 0.3-0.6 micrograms/ml after addition to the emulsion. In spite
      of this rapid decrease, somatostatin concentrations remained stable with values
      of 0.4-0.7 micrograms/ml during the follow-up period (24 h). These findings could
      be explained assuming adsorption to the surface of the container.

PMID- 1982562
TI  - Biliary hyperplasia and carcinogenesis in chronic liver damage induced in rats by
      phomopsin.
AB  - Phomopsin, a hexapeptide mycotoxin contaminant of lupin plant and seed materials,
      was administered subcutaneously to adult rats at a daily dose rate of 30
      micrograms/kg body weight (approximately 0.005 median lethal dose) for 2, 6 or 17
      wks and the development of liver damage was observed during treatment and for up
      to 2 yr after. All rats injected for 17 wks developed permanent liver damage
      characterized by nodular cirrhosis and extensive biliary hyperplasia.
      Cholangiomas developed in 60% of these rats and cholangiocarcinomas and
      hepatocellular carcinomas in 13%. Similar effects were produced in some rats
      injected for 6 wks, while in others the cessation of treatment was followed by
      almost complete regression of the liver lesions. Livers damaged by 2 wks of
      injection had fully recovered within a few wks. The permanence of the liver
      damage is relevant to the management of stock exposed seasonally to the toxin,
      while its carcinogenic potential in rats, although not high, indicates the need
      for monitoring of the phomopsin content of lupin seed or flour prepared for human
      consumption.

PMID- 1982564
TI  - Effects of drug administration in pregnancy on children's school behaviour.
AB  - Files with prescription data were used to assess possible behavioural changes in
      children, whose mothers used benzodiazepines or neuroleptic drugs during the
      second half of their pregnancy. Prescriptions, bearing the identification number
      of women resident in one district of Prague, filed in pharmacies during 1974 and
      the first three months of 1975 represent the first part of the data. During 1984,
      children born in the appropriate earlier period were searched and linked with the
      earlier prescription data. A group of 68 children with possible exposure to
      neuroleptics and a group of 15 children possibly exposed to diazepam during the
      second half of their intrauterine development were found. Two groups of 55 and 7
      children, respectively, born of mothers without exposure to these drugs, were
      chosen as controls. The teachers of classes attended by these children were
      addressed by a letter and asked to evaluate their behaviour at school. This was
      done by means of a form containing analogue scales evaluating different features
      of behaviour. Each child was compared with its control. The statistical
      evaluation with Student's t-test, regression analysis and analysis of variance
      did not reveal any significant difference between both groups and their controls.

PMID- 1982565
TI  - The selective counterstaining of the plasma membrane improves the immunoelectron
      microscopic detection of neu protein at the cell border.
AB  - The distribution of the neu protein has been studied with two monoclonal
      antibodies in a post-embedding immunogold method on glycolmethacrylate sections.
      Labeling of the cytoplasm was due to binding to mitochondrial cristae. The
      detection of label at the plasma membrane was optimized by selectively staining
      the plasma membrane with phosphotungstic acid at low pH. Strong labeling was
      observed in breast carcinoma cells and faint labeling in other tissues. Brush
      borders were also found to be reactive. neu protein can thus be localized to baso
      lateral and apical cell membranes. An important homology exists with a
      mitochondrial protein.

PMID- 1982567
TI  - Heterogeneous intrahepatic distribution of glutamine synthetase.

PMID- 1982566
TI  - Application of a new electrophoresis technique (2D cryostat section
      electrophoresis) to synovial tissue of RA patients and comparison with
      immunohistochemical staining methods.
AB  - We describe a new two dimensional electrophoresis technique which is based on the
      combination of cryostat section technology and IEF- and SDS-gel electrophoresis.
      The optimal conditions for two dimensional cryostat section electrophoresis are
      investigated. The application of this technique to synovial membranes of patients
      suffering from rheumatoid arthritis and osteoarthritis is described.

PMID- 1982568
TI  - Comparative light microscopic histochemistry of H2O2-generating and H2O2
      scavenging enzymes in extraneural rat tissues.

PMID- 1982569
TI  - Light microscopical detection of D-amino acid oxidase activity in unfixed
      cryostat sections of rat kidney and liver using the cerium-DAB-cobalt-H2O2
      procedure and a semipermeable membrane.
AB  - The two-step method for the light microscopical detection of oxidase activity
      using cerium ions and a visualization procedure with diaminobenzidine and nickel
      or cobalt ions as introduced by Anger-muller and Fahimi, has been improved.
      Inactivation by fixation and leakage of D-amino acid oxidase molecules were
      avoided by the application of unfixed cryostat sections adhered to a
      semipermeable membrane separating the sections from a gelled incubation medium.
      Optimum activity in rat kidney and liver was obtained by increasing the cerium
      concentration from 3 to 30 mM and the Tris-maleate concentration from 100 to 200
      mM in the incubation medium for the first step. D-proline was used as substrate
      and a concentration of 20 mM gave maximum activity. The second visualization step
      was performed in a medium consisting of DAB, cobalt and hydrogen peroxide. Final
      reaction product was found in a granular form in the basal part of the epithelial
      cells of the proximal tubules and in liver parenchymal cells. The activity in
      periportal areas was much higher than in pericentral areas. Cytophotometric
      analysis revealed that a 30 times higher activity could be detected when using
      the membrane technique in comparison with incubations in aqueous media. The
      specificity of the reaction was proven by a nearly complete inhibition of the
      reaction by beta-hydroxybutyrate.

PMID- 1982571
TI  - [The control of GH secretion by GHRH and somatostatin: the current status].

PMID- 1982570
TI  - [Abscessing rhombencephalitis caused by Listeria in an iummunodepressed patient].
AB  - The cerebral trunk infection by Listeria monocytogenes is a very rare process,
      with only 24 described cases and only 2 in immunodepressed patients. We present a
      new case of cerebral trunk encephalitis caused by Listeria in a patient diagnosed
      of Polyarteritis nodosa on steroids and cyclophosamide treatment and fatal
      evolution, and whose hemoculture, spinal fluid culture and cranial CT scan did
      not contribute to the diagnosis. A necrotizing lesion in the protuberance with
      mesencephalic extension was observed in the necropsy study in which intra- and
      extracellular Gram + and silver positive bacilli were detected. Since L.
      monocytogenes was suspected as the causative agent, indirect immunofluorescence
      was performed on histological preparations with hyperimmune anti-L. monocytogenes
      serum giving a clearly positive result. In our case, this technique permitted the
      etiological diagnosis in the absence of positive cultures.

PMID- 1982572
TI  - Evaluation of key gluconeogenic enzymes in experimental biliary obstruction.
AB  - In order to evaluate the usefulness of key gluconeogenic enzymes, in relation to
      the markers commonly used (alkaline phosphatase and gamma-glutamyl
      transpeptidase) for the diagnose of cholestasis the serum activity of
      phosphoenolpyruvate carboxykinase, fructose 1,6-bisphosphatase and glucose-6
      phosphatase has been measured in rats with bile-duct ligation. Among the
      gluconeogenic enzymes studied only phosphoenolpyruvate carboxykinase activity
      increased significantly in the first 48 hours after cholestasis, decreasing
      thereafter to normal values. Both alkaline phosphatase and gamma-glutamyl
      transpeptidase activities showed a very significant increase which persisted
      throughout the experiment. These results seem to indicate that in spite of the
      high organ specificity of these enzymes they do not appear to be useful for the
      diagnosis of cholestasis.

PMID- 1982573
TI  - [Draw me a health center...].

PMID- 1982574
TI  - Myocyte response to stimulation of receptors and ion channels.
AB  - Ventricular myocytes dissociated from adult rat heart and cultured chick embryo
      ventricular cells were utilized to examine mechanisms by which neurotransmitters,
      hormones, and ontogeny modulate expression and function of beta-adrenergic
      receptors and L-type calcium channels. Either freshly dissociated cells or
      cultured cells were studied by an optical-video system to characterize
      contractility and, in some instances, by a microspectrofluorimeter to determine
      [Ca2+]i as reported by fura 2. Ligand binding studies in intact cells and
      membranes were conducted with receptor and ion channel antagonists and agonists.
      Exposure of intact cells to isoproterenol produced contractile de-sensitization,
      loss of high affinity receptors from the sarcolemma and closely coupled decline
      in hormone-sensitive adenylate cyclase activity. De-sensitization was by a
      microfilament-dependent process. Down-regulation depended upon microtubular
      function. During development of the chick heart, there was an increase in number
      of dihydropyridine binding sites, taken as a measure of number of L-type calcium
      channels, at a time when sensitivity to [Ca2+]o and to Bay k 8644 declined.
      Thyroid hormone was capable of up-regulating L-type calcium channels. Prolonged
      exposure to a beta-adrenergic agonist produced coordinate down-regulation of beta
      receptors and calcium channels. Down-regulation was a cAMP-dependent process.
      Thus, the beta-adrenergic receptor and a distal component of the effector
      response coupling system, the L-type calcium channel, can be regulated
      independently and in concert by physiologically and pathophysiologically
      important mechanisms.

PMID- 1982575
TI  - Use of embryonic heart grafted in oculo to assess neurohumoral controls of
      cardiac development.
AB  - Culture of embryonic heart in the anterior eye chamber allows neurohumoral and
      genetic controls of cardiac development to be separated from the influence of
      hemodynamic load. Hearts from 12-day gestation rat embryos grafted into the
      anterior eye chamber of an adult host rat attach to the iris and become
      vascularized and innervated by collaterals from the host iris. The spontaneous
      beating of grafts is pacemaker-driven and under functional neural control. Grafts
      do not beat against a pressure load, allowing the influence of neurohumoral
      factors to be separated from altered hemodynamic load. In oculo, embryonic heart
      differentiates into mature myocardium by most morphologic and biochemical
      criteria. Mature intercalated disks and myofibrils with well-defined Z-lines and
      M-lines are observed. Mature grafts express the high levels of alpha-myosin heavy
      chain characteristic of young adult myocardium. Surgical sympathetic denervation
      of the anterior eye chamber prior to grafting of embryonic hearts compromises
      growth and increases the intrinsic pacemaker rate. Since the grafts are perfused
      by the host circulation, the hormonal milieu of the graft can be altered by
      treatment of the host. Thus, the interaction between hormones and innervation of
      grafts can be studied using the in oculo model system.

PMID- 1982577
TI  - [Round table discussion. Fertilization in vitro].

PMID- 1982576
TI  - A comparison of teicoplanin vs. cephradine and metronidazole in surgical
      prophylaxis: an interim analysis.
AB  - The preliminary results of a trial to examine and compare the safety,
      tolerability and efficacy of a single dose of teicoplanin with three doses of
      cephradine combined with metronidazole are presented in a series of 113 patients
      undergoing elective vascular surgery. There were no obvious differences in the
      infection rates and sepsis indicators in either group. Neither drug regimen
      produced any evidence of renal or hepatic damage, though the levels of three
      hepatocellular enzymes, aspartate aminotransferase (AST), alanine
      aminotransferase (ALT) and gamma-glutamyl-transferase (GGT), were seen to be
      transiently elevated, peaking 7 days post-operatively. The trial continues.

PMID- 1982578
TI  - [Round table discussion. Nursing care--routine deeds or responsible acts?].

PMID- 1982579
TI  - [Round table discussion. Trophic disorders of the skin. How to prevent a
      decubitus ulcer].

PMID- 1982580
TI  - [Round table discussion. Terminal care. Relieve the symptoms, for what quality of
      life?].

PMID- 1982581
TI  - [Round table discussion. Care of burns. Deep wounds and reconstitution of
      tissue].

PMID- 1982582
TI  - [Round table discussion. Hygiene and disinfection. Prevention of bacterial
      contamination in the hospital].

PMID- 1982583
TI  - [Round table discussion. Dependency and the problems of "old age"].

PMID- 1982584
TI  - [Round table discussion. Urinary incontinence].

PMID- 1982586
TI  - [Round table discussion. Nursing care in stomatherapy].

PMID- 1982585
TI  - [Round table discussion. The quality of temporary work. Competence, efficacy, and
      education].

PMID- 1982587
TI  - [Round table discussion. The shortage of nurses in Europe].

PMID- 1982588
TI  - [Round table discussion. Rights, duties and responsibilities of independent
      nurses].

PMID- 1982589
TI  - [Fifth colloquium of the "Cent Gardes"].

PMID- 1982590
TI  - [European meetings of nursing administrators. The first day].

PMID- 1982591
TI  - Ultrastructural changes in the abdominal midgut of the mosquito, Culiseta
      melanura, during the gonotrophic cycle.
AB  - Abdominal midguts of the mosquito, Culiseta melanura, were examined by light and
      electron microscopy 1 hr-14 days days after blood feeding. Epithelial cells were
      drastically altered from columnar to squamous in form after engorgement, and
      returned to columnar by day 4 after feeding. Accumulation of mitochondria along
      brush borders of digestive cells, followed by the appearance of large secondary
      lysosomes, accompanied blood digestion. Evidence was obtained that myelin-like
      material in the lysosomes, probably the result of mitochondrial autolysis, is
      extruded into the lumen. Digestive cells resumed their pre-blood meal appearance
      by 10-14 days post-engorgement. Regenerative cells were scattered throughout the
      basal portion of the epithelium, along with endocrine cells. Other midgut cells
      containing large, microvilli-lined apical cavities were identified in most
      specimens. No evidence of division or differentiation was obtained for any cell
      types.

PMID- 1982592
TI  - Rapid detection of Japanese encephalitis virus by immunofluorescence after
      intracerebral inoculation of mosquito larvae.

PMID- 1982594
TI  - [Antihypertensive drugs and kidney function].

PMID- 1982593
TI  - Fatal infectious mononucleosis in a family.
AB  - Two male siblings, one aged five and a half months (SB), and the other aged six
      months (VB), with fatal infectious mononucleosis phenotype of the X-linked
      lymphoproliferative syndrome, which resulted in the death of both infants, are
      presented. Both patients had been healthy, one until the age of five and a half
      months, and the other until the age of six months. Then, they developed a
      maculopapular rash, hepatosplenomegaly and lymphadenopathy. In one sibling, the
      serum IgG level was low, the IgM and IgA levels were high, and the proportion of
      E-rosette forming cells (E-RFC) and in vitro proliferative response to PHA were
      normal. In the other sibling, however, the serum IgG level was normal, the IgM
      and IgA levels were high and the stimulation index for proliferative response to
      PHA was reduced due to increased spontaneous blastogenesis. Anti-EBV antibodies
      were negative in both siblings, except for the IgM anti-VCA in V.B. A lymph node
      specimen could be studied in one infant and was found to be positive for the EBV
      genome. Postmortem histopathological findings included the absence of cortico
      medullary differentiation and identifiable Hassal's corpuscles in the thymus and
      depletion of T-dependent regions of lymph nodes and spleen in V.B. Atypical
      mononuclear cell infiltration was detected in the portal areas of the postmortem
      liver biopsy in S.B.

PMID- 1982595
TI  - [The regression of left ventricular hypertrophy during the treatment of
      hypertension with different classes of beta blockers].
AB  - 156 patients with hypertension II stage according to the WHO classification and
      left ventricular hypertrophy proved by echocardiographic examination were treated
      in the course of one year with various class beta-blockers. At the end of the
      first month of treatment the thickness of the interventricular wall, of the
      posterior wall and of the left ventricular muscular mass does not change. Till
      the end of the 6th month the thickness of all these three decreases (p less than
      0.0001). The additional decrease at the end of the 12-ve month of treatment is
      insignificant to that at the 6th month. The mean percentage decrease is greater
      by treatment with beta-blockers without inner sympathomimetic activity than with
      beta-blockers with such activity. There is no difference in relation to the
      cardioselectivity of the drug. Till the end of the 12-ve month of treatment the
      left ventricular muscular mass becomes normal in 35.9% of the patients on the
      background of normalized arterial pressure. In 6.4% of the patients the left
      ventricular muscular mass does not change in spite of the decrease of the
      arterial pressure. The percentage reduction of the left ventricular muscular mass
      correlates with the percentage decrease of the systolic (r = 0.603), diastolic (r
      = 0.457) arterial pressure and the heart rate (r = 0.636).

PMID- 1982596
TI  - [The role of intracellular processes in regulating neuronal sensitivity to
      acetylcholine].
AB  - Intracellular regulatory mechanisms of neuronal response to acetylcholine were
      studied on intracellularly perfused isolated neurones of Lymnaea stagnalis using
      voltage-clamp technique. It was found that at the change of concentration of free
      intracellular Ca2+ from 0.06 to 0.7 microM the inhibitory effect of
      intracellularly added serotonin depends on Ca2+, and the modulation of
      acetylcholine responses by intracellular serotonin is unchanged. The blockers of
      calmoduline trifluoperazine and W-7 inhibit inward acetylcholine current at both
      intra- and extracellular introduction. Possible mechanisms mediating the effect
      of intracellularly added serotonin on the membrane cholinoreceptors of neurones
      are discussed.

PMID- 1982597
TI  - [The multiplicity of neurotransmitters: the functional significance].
AB  - The generally accepted synaptic concept is an idealization based on two major
      assumptions essential for a system of neurone to be orderly organized: firstly,
      specificity of anatomical connections between neurones is assumed, and, secondly,
      it is postulated that the signal is transmitted via isolated compartment of
      extracellular space, the synaptic cleft. In the framework of this conceptual
      model, systems can be built using a single sort of signal molecules, and
      knowledge on diversity of neurotransmitters remains unconceptualized. To provide
      that the signal is properly delivered to a due address, neurones can however
      equally utilize the chemical mode of addressing. According to an alternative
      conceptual model proposed by the author, orderliness of a neuronal system is
      based on plurality of signal molecules. To describe the idealized elementary unit
      of heterochemical integration, the term "Heteron" is introduced. Heteron is
      defined as the network of individually specific neurones differing in their
      respective transmitters. It is postulated that (i) the transmitter situation is
      changed evenly throughout the heteron and (ii) responses of sensitive targets to
      a specific transmitter situation are composed into a well co-ordinated whole. The
      functional repertory of a heteron containing n neurones (i.e. n transmitters)
      will thus include at least n integrated states. The conceptual synapse
      corresponds to a theoretical limit of the heteron (when n = 1). It is suggested
      that primitive, simpler nervous systems roughly correspond to a single heteron
      while evolved brains and cords include multiple units of heterochemical
      integration.

PMID- 1982598
TI  - [Indicators of the dexamethasone test in patients with affective disorders after
      administration of neuro- and psychotropic drugs].
AB  - A study was made of the effect of the antidepressants desmethylimipramine,
      mianserin, befol, alpha-adrenoblockers of pyrroxane, phentolamine as well as
      tryptophan, clonidine, propranolol, salbutamol, and the benzodiazepine
      tranquilizer phenazepam on the dexamethasone test (DMT). The drugs possessing
      antidepressive effect in nonsuppressors improved the parameters of the DMT at the
      expense of decreasing the postdexamethasone level of cortisol while the serotonin
      positive drugs tryptophan and befol did not produce any effect on the
      predexamethasone level of cortisol whereas mianserin, desmethylimipramine,
      pyrroxane and phentolamine slightly reduced the predexamethasone level of
      cortisol, influencing to a greater degree the postdexamethasone level. In
      suppressors, the serotonin-positive drugs deteriorated the parameters of the test
      whereas the agents affecting the adrenergic transmission did not change it.
      Phenazepam materially lowered the level of cortisol in suppressors and
      nonsuppressors. It is concluded that the antidepressive action is realized via
      the serotoninergic systems and alpha-adrenoreceptors.

PMID- 1982599
TI  - [Joint session sponsored by 2 academies on the history of Russian psychiatry].

PMID- 1982600
TI  - Side effects of neuroleptics in clinical practice.
AB  - The authors analyzed a set of 65 women patients treated with neuroleptics in a
      period of two years. In the study are assessed in detail the side effects in
      neuroleptic therapy. The results of the research were generalized in the form of
      factors according to the international Structured Adverse Effects Rating Scale.

PMID- 1982601
TI  - [The importance of the blocking of ganglionic N-cholinoreceptors for labor
      induction].

PMID- 1982602
TI  - [Dormicum, aneksat and their use in obstetrical and gynecological operations].

PMID- 1982603
TI  - Molecular studies on LAK cells.
AB  - We have developed a culture system for long-term growth of human LAK cells
      exhibiting an elevated, wide-spectrum anti-tumor cytotoxicity. The phenotypic and
      molecular properties of the final LAK cell populations indicated that they
      consist of three main types: a) NK-like lymphocytes (type I): NKH-1+, Ti
      alpha/beta-, Ti gamma/delta-, CD3-lymphocytes carrying the germline configuration
      of all TCR genes and expressing variable amount of the 1.0 beta mRNA and variably
      sized T delta transcripts; b) gamma/delta-like T lymphocytes (type II) NKH-1+, Ti
      alpha/beta-, Ti gamma/delta+, CD3+ lymphocytes carrying polyclonal rearrangements
      of the gamma and delta genes and expressing high levels of mature gamma and delta
      transcripts; c) alpha/beta-like T lymphocytes (type III): NKH-1+, Ti alpha/beta+,
      Ti gamma/delta-, CD3+ lymphocytes carrying rearrangements of all TCR genes and
      expressing high levels of mature alpha and beta transcripts. We took advantage of
      the high number of available LAK cells to clarify: 1) the origin of the NK-LAK
      delta transcripts. delta gene expression in LGL, NK clones and type I LAK
      cultures revealed six delta transcripts (3.5, 3.1, 2.2, 2.0, 1.5 and 1.3 kb),
      which varied in number and relative abundance in the different samples. None of
      the six known V delta was expressed and the delta locus was retained in its
      germline configuration suggesting that the delta expression is due to a partially
      rearranged or germline transcripts; 2) the origin of the NK-LAK truncated T beta
      transcript. We isolated two different clone types from a type I LAK cell cDNA
      library: a) J-C clones consisting of one of three J beta regions and the
      corresponding C beta 1 or C beta 2 regions; b) X-J-C and C-X clones, containing
      as yet unidentified (X) sequences. The presence of RSSs in J-C clones suggests
      that they derive from mRNAs transcribed from a promoter in the 5'J. Nucleotide
      analysis demonstrated that only one of the isolated clones had the potential to
      code a short T beta protein.

PMID- 1982604
TI  - Susceptibility of multidrug-resistant human T-lymphoblastoid CEM cell line to
      cell-mediated cytolysis.
AB  - The using of multidrug-resistant (MDR) cell variants represents one of the major
      obstacles to an effective cancer therapy based on the administration of cytotoxic
      compounds. In the present article we describe experimental procedures able to
      eradicate, in vitro, by using specific immunological reagent, MDR tumor cells. In
      an allogeneic cell system, natural killer (NK) and lymphokine activated killer
      (LAK) cells result effective against MDR variants of the human T-lymphoblastoid
      CEM cell line. Surprisingly effector cells discriminate in their lytic capacity
      target cells possessing a MDR phenotype. A direct relationship between the degree
      of relative resistance shown by target cells and cytotoxic level exerted by
      peripheral lymphocytes stimulated and non by IL-2 was observed. The preincubation
      of MDR cell variants with a monoclonal antibody (MoAb57) specific for an
      extramembranal epitope of P-glycoprotein induced, in presence of effector cells,
      a strong antibody-dependent cell-mediated cytolysis (ADCC). This phenomenon was
      observed only in MDR variants over-expressing in concomitance with drug
      resistance high level of P-glycoprotein. In identical experimental conditions,
      drug-sensitive parental cells does not show valuable ADCC.

PMID- 1982605
TI  - [Systemic effects of eyedrops].

PMID- 1982606
TI  - Adrenergic vasomotion in the coronary microcirculation.
AB  - The goal of this study was to determine the alpha-adrenergic receptor subtype(s)
      responsible for constriction at different microvascular levels in the coronary
      circulation. To accomplish these goals, the epicardial coronary microcirculation
      of intact beating hearts was viewed through an intravital microscope using
      stroboscopic epi-illumination. An initial study was designed to establish sites
      of alpha-adrenergic constriction to norepinephrine in preparations with intact
      vasomotor tone. For the primary experimental goal, coronary microvascular
      responses to selective alpha 1-adrenergic (phenylephrine) or alpha 2-adrenergic
      (BHT-933) agonists were evaluated, when coronary autoregulatory escape mechanisms
      were blunted during hypoperfusion. Infusion of norepinephrine decreased diameter
      of arterial vessels greater than 100 microns in diameter, but downstream coronary
      arterioles dilated significantly, representing autoregulatory escape from
      adrenergic vasoconstriction. In studies designed to examine the adrenergic
      receptor subtype (during hypoperfusion), phenylephrine produced modest
      constriction of vessels throughout the microcirculation (6-9% decrease in
      diameter), whereas BHT-933 produced marked constriction of small coronary
      microvessels, those less than 100 microns in diameter (24% decrease in diameter).
      From these results we conclude: 1) norepinephrine infusion causes disparate
      responses in the coronary microvasculature: constriction occurs in vessels
      greater than 100 microns in diameter, but dilation, via autoregulatory escape,
      predominates in vessels less than 100 microns in diameter; 2) alpha 1-adrenergic
      receptors are located in coronary arterioles and arteries; and 3) alpha 2
      adrenergic receptors are preferentially located in small coronary arterioles.
      Thus, alpha 1- and alpha 2-adrenergic activation can produce dissimilar
      constrictor effects in the coronary microcirculation during hypoperfusion.

PMID- 1982607
TI  - Neurohumoral regulation of coronary collateral vasomotor tone.
AB  - As a result of gradual coronary occlusion, coronary collaterals are stimulated to
      develop. This maturation process involves not only dilatation of the vessel, but
      the development of new vascular smooth muscle. Experiments have been performed to
      examine vasomotor characteristics of mature coronary collaterals from dogs 3 to 6
      months following ameroid constrictor placement. Studies in Langendorff blood
      perfused hearts have shown that transcollateral resistance does not change during
      either the administration of alpha 1- or alpha 2-adrenergic agonists. Isolated
      collateral vessels studied as rings in organ chambers do not constrict to either
      alpha 1- or alpha 2-adrenergic agonists. These studies show that mature
      collateral vessels are not likely to possess functioning alpha-adrenergic
      receptors. Subsequent experiments using a cover slip autoradiographic ligand
      binding approach have demonstrated a population of beta-adrenergic receptors on
      mature coronary collaterals. Studies of isolated collaterals have demonstrated
      beta-adrenoceptor-mediated relaxation that appears due to a population of mixed
      beta 1- and beta 2-adrenergic receptors. Subsequent studies have demonstrated
      that mature collateral vessels are hyperresponsive to the vasoconstrictor effects
      of vasopressin and that concentrations of vasopressin which may be encountered in
      pathophysiologic conditions can markedly attenuate coronary collateral perfusion.
      Finally, the microcirculation of the collateral-dependent myocardium develops
      endothelial cell dysfunction. This results in impaired endothelium-dependent
      relaxations to adenosine diphosphate and acetylcholine and enhanced
      vasoconstriction to vasopressin. These alterations of the coronary circulation
      may have important implications regarding neurohumoral regulation of myocardial
      perfusion in collateral-dependent myocardium.

PMID- 1982608
TI  - Alpha-adrenergic regulation of myocardial performance in the exercising dog:
      evidence for both presynaptic alpha 1- and alpha 2-adrenoceptors.
AB  - New evidence supporting both presynaptic alpha 1- and alpha 2-adrenoceptors
      playing a role in the regulation of myocardial contractile performance in the
      exercising dog is reviewed. Studies utilized chronically instrumented dogs having
      sonomicrometers for the measurement of regional wall thickening and transducers
      for the measurement of left ventricular and systemic hemodynamics. During steady
      state exercise, either the selective alpha 1-adrenoceptor blocker prazosin (80
      micrograms/kg) or the selective alpha 2-adrenoceptor blocker idazoxan (80
      micrograms/kg) was infused into the left atrium while exercise continued.
      Immediately following the administration of either alpha-adrenoceptor blocking
      agent, there were substantial increases in heart rate, left ventricular dP/dt and
      regional contractile function as assessed using sonomicrometers, and
      norepinephrine release by the myocardium increased substantially. beta-adrenergic
      blockade prevented the heart rate and contractile effects of either alpha 1- or
      alpha 2-adrenoceptor blocker whereas norepinephrine release was further enhanced.
      These effects could not be attributed to baroreceptor unloading. In dogs studied
      under resting conditions with norepinephrine infusion to produce an increase in
      dP/dt similar to that observed during treadmill exercise, no sympathetic
      augmentation was observed following either alpha-blocker. Together, these studies
      provide evidence that both alpha 1- and alpha 2-adrenoceptors participate in the
      modulation of sympathetic neuronal norepinephrine release in the canine
      myocardium.

PMID- 1982609
TI  - Alpha 2-adrenergic coronary constriction in ischemic myocardium during exercise.
AB  - The effect of either selective alpha 1- or alpha 2-adrenoceptor blockade on
      ischemic myocardial blood flow and function was examined in beta-blocked dogs
      trained to run on a motor-driven treadmill. The animals were instrumented with
      sonomicrometers for the assessment of regional systolic wall thickening (%WTh) of
      the left ventricle. For drug infusion, an intracoronary catheter was implanted in
      the circumflex coronary artery and a hydraulic cuff was placed proximally around
      the artery. Following systemic beta-blockade with 0.8 mg/kg propranolol, an acute
      stenosis of the circumflex coronary artery inflated during exercise induced
      severe dysfunction in the posterior wall. Intracoronary infusion of 80
      micrograms/kg of the selective alpha 2-adrenoceptor blocking agent idazoxan
      improved posterior wall (PW)-%WTh from 5.1 +/- 1.6 to 10.8 +/- 2.8% (p less than
      0.06) and regional myocardial blood flow (radiolabelled microspheres) in the
      subendocardium of the posterior wall from 0.17 +/- 0.05 to 0.45 +/- 0.30
      (ml/min)/g (p less than 0.05). No increases in regional blood flow and regional
      myocardial function were observed after infusion of the selective alpha 1
      adrenoceptor blocking agent prazosin (20 micrograms/kg) under the same
      experimental conditions. It is concluded that during severe ischemia, significant
      postjunctional alpha 2-adrenoceptor mediated coronary vasoconstriction exists.
      Regional alpha 2-adrenoceptor blockade, but not alpha 1-adrenoceptor blockade is
      effective in reducing regional ischemia and dysfunction by attenuating
      sympathetic vasoconstriction in the conscious dog.

PMID- 1982610
TI  - Effects of beta-blockade on the incidence of ventricular tachyarrhythmias during
      acute myocardial ischemia: experimental findings and clinical implications.
AB  - Myocardial ischemia and infarction are the most common substrates for life
      threatening ventricular tachyarrhythmias. Experimental and clinical evidence
      suggests that enhanced activity of the sympathetic nervous system plays an
      important role in the genesis of ischemia-related arrhythmias. In animal
      experiments, beta-blockers display significant antifibrillatory effects during
      the acute phase of myocardial ischemia. Preconditions for their antifibrillatory
      effects are high serum- and tissue-concentrations, and absence of a significant
      partial agonist activity. During the delayed phase of ischemic arrhythmias which
      starts 6-8 h after coronary occlusion, beta-blockers gain significance as
      antiarrhythmic and potentially antifibrillatory drugs, if sympathetic activity is
      enhanced. The presently available evidence suggests that the potentially
      antifibrillatory effects of beta-blockers are at least one of the major
      mechanisms by which these drugs may decrease mortality when given
      prophylactically in patients after myocardial infarction. However, it remains to
      be explained why beta-blockers, in a great number of prospective randomized
      trials, have reduced the incidence of sudden death only by an average of about
      30%. This may be the result of their "specific" mechanisms acting in the setting
      of acute myocardial ischemia with enhanced adrenergic tone, whereas in the
      remaining patients other mechanisms such as a chronic arrhythmogenic substrate
      may be operative. A clearer separation of these various mechanisms seems
      mandatory in order to allow a more specific "targeted" administration of beta
      blockers. This is the more important since none of the available prospective
      studies that used antiarrhythmic agents has shown an improvement of prognosis,
      but, instead showed a worsening of the mortality rate.

PMID- 1982611
TI  - Heart rate and beta-adrenergic mechanisms in acute myocardial infarction.
AB  - Increased heart rate is an independent predictor of mortality in patients with
      acute myocardial infarction. Elevated heart rate is due to increased sympathetic
      activity and/or decreased parasympathetic activity. In placebo-controlled trials
      beta-blockers are known to reduce mortality as well as morbidity and these
      effects are most evident among patients with elevated heart rate. Studies on
      circadian variation have demonstrated that there is an increased sympathetic
      activity in the morning as well as a more frequent onset of ischemic attacked
      including acute myocardial infarction and sudden death. There seems to be a close
      relationship between increased sympathetic activity and the onset of ischemic
      events which can be prevented by prophylactic institution of a beta-blocker.

PMID- 1982612
TI  - Coronary vasomotor tone in large epicardial coronary arteries with special
      emphasis on beta-adrenergic vasomotion, effects of beta-blockade.
AB  - Changes in coronary vasomotor tone of large epicardial coronary arteries today
      can be assessed quite accurately by exact measurements of coronary diameters
      applying computer assisted systems. The effect of various vasodilators (nitrates,
      calcium antagonists, EDRF-dependent compounds) was tested in this way. It appears
      that normal coronary artery segments reach a maximum of dilator reserve with an
      increase of luminal diameter of approximately 30-40%; different patterns of
      kinetics were, however, encountered. beta-Blocking agents, both non-selective
      (propranolol) and selective (atenolol), were found to lead to a gradual
      vasoconstriction, i.e., a decrease in diameter by approximately 20-25% over 20
      min, an effect which is overcome by nitrates. New beta-blocking compounds with
      vasodilator properties, such as celiprolol, show no constriction. The
      vasoconstrictor effect of propranolol and atenolol may not only be due to the
      decrease of flow following the drop in myocardial oxygen consumption, but could
      also reflect an unopposed alpha-adrenergic tone. The clinical aspects of this
      observation are discussed.

PMID- 1982613
TI  - Alpha- and beta-adrenergic control of large coronary arteries in conscious
      calves.
AB  - Large and small coronary arteries are subject to control by alpha- and beta
      adrenergic mechanisms. However, controversy exists as to the distribution and
      physiological effects of alpha- and beta-adrenergic receptor subtypes in large
      coronary arteries. Studies in our laboratory have addressed these questions in
      conscious calves, chronically instrumented to measure large coronary artery
      diameter and coronary blood flow. Additionally, adrenergic receptor subtype
      distribution was determined using ligand binding assays in membrane preparations
      isolated from large coronary arteries of calves. Physiological results
      demonstrate, in contrast to the results of most previous studies, that both alpha
      1- and alpha 2-adrenergic receptors elicit constriction of the large coronary
      artery. Studies with ganglionic blockade indicate that the constriction was
      unaltered by autonomic reflexes or presynaptic release of neurotransmitters.
      Selective beta-adrenergic receptor activation demonstrated that both beta 1- and
      beta 2-adrenergic receptors elicit dilation of large coronary arteries, and that
      the vasodilation was direct, i.e., it was not mediated by increases in coronary
      blood flow. Biochemical characterization of adrenergic subtype density indicated
      the presence of both alpha 1- and alpha 2-, as well as beta 1- and beta 2
      adrenergic receptor subtypes. Thus, both biochemical and physiological data
      support the concept that large coronary arteries are regulated by both alpha 1-
      and alpha 2-, as well as beta 1- and beta 2-adrenergic receptor subtypes.

PMID- 1982614
TI  - Comparative effects of loratadine and azatadine in the treatment of seasonal
      allergic rhinitis.
AB  - The efficacy and safety of loratadine 10 mg once daily were compared with
      azatadine 1 mg twice daily in controlling symptoms of seasonal allergic rhinitis.
      The study was a randomized, double-blind, parallel-group design involving 34
      patients receiving either loratadine or azatadine for 14 days. Both treatments
      were effective in relieving the histamine-mediated symptoms of seasonal allergic
      rhinitis. At baseline, 100% and 93% of the patients in the loratadine and
      azatadine treatment groups, respectively, had moderate or severe symptoms of
      disease; at endpoint of treatment 80% of the patients in the loratadine treatment
      group and 92% of those in the azatadine treatment group had mild or no disease
      symptoms. Sedation was reported by fewer patients in the loratadine treatment
      group than in the azatadine group. Thus loratadine is an effective and safe
      antihistamine when given once daily for the symptomatic relief of seasonal
      allergic rhinitis.

PMID- 1982615
TI  - Effect of neonatal undernutrition upon cerebroside sulfate degradation in the
      developing rat brain.
AB  - In order to find out if the decreased accumulation of cerebroside sulfates
      observed in 21-d-old undernourished rats was in part the result of an increased
      rate of catabolism of these galactolipids, the in vivo degradation of brain
      cerebroside sulfates was studied in 18-d-old normal and undernourished rats. Two
      hours after the intracranial injection of the precursor (0 time), the animals
      were injected intraperitoneally with unlabeled sodium sulfate. Labeled
      cerebroside sulfates were measured in the brain up to 48 h after the chase. In
      normal animals, the radioactivity decreased at 24 h and 48 h to 55% and 41%,
      respectively, of the value obtained at 0 time. In undernourished animals,
      degradation was negligible, since the radioactivity attained at 0 time remained
      almost constant up to 48 h. The lack of in vivo degradation of cerebroside
      sulfates observed in the starved rats cannot be explained by a deficiency of
      Arylsulfatase A, since the pattern of activity of the enzyme was similar in both
      groups of animals.

PMID- 1982617
TI  - Fungal infections in the nineties and the role of oral therapy. Proceedings of a
      symposium. London, 25 November 1989.

PMID- 1982616
TI  - [Somatostatin and/or total parenteral nutrition for the treatment of intestinal
      fistulas].
AB  - 61 patients with postoperative enterocutaneous fistulas of the small intestine,
      were admitted to the Intensive Care Unit from 1983 to 1989 and divided in two
      groups. Group A (n = 46) was treated with Total Parenteral Nutrition (TPN), while
      B (n = 15) received a combination of TPN and Somatostatin. The reduction of
      fistula output was significantly greater in group B. Spontaneous closure was
      observed in 30.4% of the cases in group A and in 53.3% in group B. A significant
      difference in the time taken to close the fistula between group A and B (29.7 +/-
      18 versus 11.1 +/- 1.6 days) was observed.

PMID- 1982618
TI  - [Ultrasound diagnosis 90. Three-country-meeting, Bregenz 3-6 October 1990].

PMID- 1982619
TI  - [3d International Symposium on gallbladder lithotripsy, Munich, 13-15 September
      1990].

PMID- 1982620
TI  - [HR/QT ratio during ergometric test: influence of ischemia and beta blocking
      therapy].
AB  - The aim of this study was to analyze the HR/QT relation during exercise in a
      group of patients with effort angina (Group B) in comparison with the same
      relation obtained in a group of normal subjects (Group A) comparable for age and
      sex. The regression analysis was carried out separately during effort in upright
      position and during rest in clinostatic position to avoid influences on QT by the
      patient's posture. During effort in patients of the Group B the regression shows
      a lower value of the slope and of the intercept (p less than 0.001) than those
      obtained in the subjects of the Group A. A similar behaviour is shown also from
      the regressions obtained during rest in the same groups. Thus at the highest HRs
      we observed a longer QT in the Group B. Moreover QT of ischemic patients in the
      presence of ECG signs of ischemia (ST less than or equal to 1 mm) resulted
      significantly longer (p less than 0.01) either during effort and at rest, respect
      to that obtained in Group A at comparable HRs. The analysis of the regression
      HR/QT after administration of atenolol 100 mg per os in a subgroup of patients of
      Group B clearly shows a less prolonged QT at the highest HRs where ECG ischemia
      frequently appears. This fact is demonstrated by the presence of a higher slope
      (p less than 0.05) respect to that obtained in the same group without therapy. In
      conclusion, myocardial transient ischemia provokes a longer QT in patients with
      ischemic heart disease in comparison with normal subjects. Acute therapy with
      atenolol per os is able to condition the regression HR/QT showing a relative
      shortening of QT at the highest HRs respect to that carried out in the same
      patients in absence of therapy.

PMID- 1982621
TI  - [Hemodynamic effects of the nitroprusside test in chronic congestive heart
      failure treated with long-term beta blocking therapy].
AB  - In patients with congestive heart failure (CHF) sympathetic reflexes are
      attenuated because of down regulation of beta receptors. Many Authors suggest
      that betablockers therapy can be useful in selected patients. We wanted to test
      if betablockers therapy could modify sympathetic reflex during nitroprusside
      test. We studied 20 patients: 10 were healthy volunteers and 10 were affected by
      CHF of different origin. They were divided in 4 groups in relation to therapy.
      During nitroprusside infusion we evaluated the following parameters: heart rate
      (HR), mean arterial pressure (MAP), mean pulmonary arterial pressure (MPAP),
      pulmonary capillary wedge pressure (PCWP), right atrial pressure (RAP), cardiac
      index (CI), systemic vascular resistance (SVR), pulmonary vascular resistance
      (PVR). In normal subjects we observed that the heart rate increased and the PAM
      and SVR decreased significantly. Betablockers therapy did not modify hemodynamic
      response of PAM and SVR, while we did not find any modification of the heart
      rate. In patients with CHF we observed a decrease of PAM, MPAP, SVR and PVR.
      Betablockers therapy in CHF did not modify the hemodynamic response to
      nitroprusside test. This effect is probably due to beta adrenergic receptor down
      regulation that decrease the responsiveness to sympathetic stimulation evoked by
      vasodilatation.

PMID- 1982623
TI  - [The role of therapeutic laparoscopy in the surgical treatment of intra-abdominal
      testes in children].
AB  - Over a period of four years (September 1986 to September 1990), 32 impalpable
      testes were found in 24 cryptorchid boys at Sainte-Justine Hospital, Montreal. 11
      (34%) of the impalpable testes were intra-abdominal. Of these, 5 testes were
      hypoplastic and were removed, 3 by a traditional inguinal transperitoneal
      orchiectomy and 2 by laparoscopy; 2 testicles were brought down by classic
      orchiopexy whereas two others underwent a Fowler-Stephens procedure. One of these
      underwent preliminary laparoscopic clipping of the spermatic vessels followed six
      months later by open surgery to bring the testis down on the vas and deferential
      artery and its well-developed collateral circulation. One patient underwent a two
      stage open orchiopexy and another had unilateral testicular autotransplantation.
      The literature is reviewed and surgical indications for therapeutic laparoscopy
      are discussed.

PMID- 1982624
TI  - [Non-palpable testes. Apropos of 161 cases].
AB  - A series of 161 boys with 178 impalpable testes is reviewed. Extended inguinal
      exploration was the main form of investigation and treatment. Hormone injections
      and studies were performed in bilateral cases. Sonography was unhelpful.
      Laparoscopy was not used. Impalpables testes account for 7% of all boys with an
      anomaly of testicular descent and 8.5% of operated boys. One hundred and twenty
      six testes were found, 58 in the abdomen, 68 in the inguinal canal. Thirty one
      nodular vestige were found and all 25 with histopathology were spermatic duct
      residue. In 21 boys no trace of testes or spermatic duct remnant were found.
      Ninety five testes were successfully brought to the scrotum with one (85) or two
      (10) stage procedure. Anomalies of the upper urinary tract in 13 of 21 cases
      without testes or spermatic duct remnant were very rare. In bilateral cases it
      looks better to search a testes whatever the biological responses to gonadotropin
      stimulation.

PMID- 1982622
TI  - A novel 1745-dalton pyroglutamyl peptide derived from chromogranin B is in the
      bovine adrenomedullary chromaffin vesicle.
AB  - 1. Following the recent demonstration of a glutaminyl cyclase activity localized
      in adrenomedullary chromaffin vesicles, an assay was developed to isolate and
      characterize posttranslationally modified peptides from this tissue which contain
      pyroglutamate. This assay consisted of spectrometric identification of peptides
      before and after enzymatic removal of pyroglutamyl residues. 2. Using this
      procedure, a pyroglutamyl peptide (BAM-1745) was isolated and sequenced and was
      shown to be a significant component of adrenomedullary secretory vesicles. 3. A
      computer search through the Swiss-Prot protein sequence database revealed a 93%
      identity of BAM-1745 and a fragment of human chromogranin B (Gln580-Tyr593).

PMID- 1982625
TI  - Advanced apheresis course and Fourth National Component Symposium, February 1990.

PMID- 1982626
TI  - Neurochemical profile of eltoprazine.
AB  - In this paper we present the neurochemical profile of eltoprazine, a drug that
      specifically inhibits offensive aggression. Eltoprazine interacts selectively
      with serotonin (5-HT) receptor subtypes (Ki-values for 5-HT1A, 5-HT1B and 5-HT1C
      receptors are 40, 52 and 81 nM respectively). Affinity for other neurotransmitter
      receptors is much lower (Ki-values greater than 400 nM) than for 5-HT1 receptors.
      The selective interaction with 5-HT1 receptor subtypes is confirmed by in vitro
      autoradiographic studies using radiolabelled eltoprazine. The overall
      distribution of [3H]eltoprazine bears a strong resemblance to the localization of
      5-HT1 binding sites labelled by [3H]5-HT, although some differences are observed.
      Eltoprazine (1 microM) inhibits the forskolin stimulated c-AMP production in
      hippocampus slices of the rat, indicating an agonistic action on the 5-HT1A
      receptor. The K+ stimulated release of 5-HT from rat cortex slices is inhibited
      by eltoprazine (pD2 = 7.8). The maximal response, however, was clearly less than
      that of the full agonist 5-HT, indicating partial agonistic activity on the 5
      HT1B receptor (alpha = 0.5). Eltoprazine has a weak antagonistic action (IC50 = 7
      microM) on the 5-HT1C receptor as revealed by inhibition of the 5-HT-induced
      accumulation of inositol phosphates in the choroid plexus of the pig. In vivo,
      eltoprazine reduces 5-HIAA levels in the striatum, without affecting the 5-HT
      levels. Eltoprazine also reduces the 5-HT synthesis rate as shown by 5-HTP
      accumulation after decarboxylase inhibition. These data indicate that eltoprazine
      acts as a 5-HT agonist in vivo in a dose range that affects aggressive behaviour
      (0.3-3 mg/kg p.o.). Taken together from a variety of neurochemical studies there
      is strong evidence both in vitro and in vivo that the pharmacological actions of
      eltoprazine can be attributed to an interaction with the 5-HT system, most
      probably via a (partial) agonistic action on 5-HT1A and 5-HT1B receptors.

PMID- 1982627
TI  - [2nd National Congress of Gynecology and Obstetrics. October 29-November 2, 1990,
      Guadalajara, Jalisco].

PMID- 1982628
TI  - Determinants of acid secretion.
AB  - Acid secretion is regulated by hormonal factors acting peripherally and
      centrally, as well as neural factors. Gastrin and histamine are the two most
      important peripheral hormonal stimulants, while the vagus is the predominant
      nerve affecting acid secretion. Meal related acid secretion occurs in three
      phases: cephalic, gastric and intestinal. Acid secretion is stimulated in the
      first two phases while it is inhibited in the intestinal phase. Proteins are
      potent acid stimulants but carbohydrates and fats are inhibitors. Tea, coffee,
      milk and alcohol are acid stimulants; on the other hand the damaging influence of
      spices on the stomach may not be related to increased acid secretion.
      Psychological stress has a variable effect. The effect of Helicobacter pylori
      infection on acid secretion is being elucidated. Many drugs modifying acid
      secretion are available and are useful in the treatment of acid peptic disease.

PMID- 1982629
TI  - Conformational analyses on histamine H2-receptor antagonists.
AB  - In a series of compounds with H2-antihistaminic activity, a conformational
      analysis was performed based on force field calculations. The drugs studied were
      cimetidine, ranitidine, famotidine, roxatidine and the conformationally more
      restricted ICI127032. For the compounds containing a flexible chain, the local
      minima conformations and the global minimum conformation were calculated. These
      conformations were used for a systematic structural comparison with all
      energetically allowed conformations of the ICI derivative, with regard to the
      best fit of the common structural features. In this way a pharmacophore could be
      developed consisting of four parts: (1) a polar planar group, uncharged at
      physiological pH; (2) a hydrophobic part formed by aromatic systems or flexible
      chains; (3) an--under physiological conditions--protonated nitrogen atom; and (4)
      a substructure, which contains a hydrogen bond donor site and a hydrogen bond
      acceptor site in a specific spatial arrangement.

PMID- 1982630
TI  - [Determination of P-170 using C-219].

PMID- 1982631
TI  - Assessment of multidrug resistance (MDR) by immunohistochemistry in breast
      carcinoma. Correlation with tumor size and regional node status.

PMID- 1982632
TI  - Mammary carcinoma. A multiparametric (MDR-P-glycoprotein expression, regional
      node status, tumor cells kinetics and receptor status) and immunohistochemical
      study.

PMID- 1982633
TI  - Evidence that the mechanism of gene exchange in Trypanosoma brucei involves
      meiosis and syngamy.
AB  - All pairwise combinations of three cloned stocks of Trypanosoma brucei (STIB
      247L, STIB 386AA and TREU 927/4) were co-transmitted through tsetse flies
      (Glossina morsitans) and screened for the production of hybrid trypanosomes.
      Clones of metacyclic and bloodstream trypanosomes from flies harbouring mature
      infections containing hybrid trypanosomes were established and screened for
      several isoenzyme and restriction fragment length polymorphisms. For each of the
      three combinations of parents, some progeny clones were observed to be of a
      phenotype and genotype indicating that genetic exchange had occurred during
      development of the trypanosomes in flies. These hybrid clones shared three
      salient features: (1) where the parents were homozygous variants the progeny were
      heterozygous, (2) where one of the parents was heterozygous, allelic segregation
      was observed and (3) the progeny clones were shown to be recombinant when two or
      more markers for which one of the parents was heterozygous were examined. These
      results are consistent with the progeny being an F1 in a diploid mendelian
      genetic system involving meiosis and syngamy. Our observations show that all
      possible combinations of the three stocks may undergo genetic exchange. A marker
      analysis of a series of clones each derived from single metacyclic trypanosomes
      showed that individual flies transmit a mixture of trypanosome genotypes
      corresponding to F1 progeny and to parental types, indicating that genetic
      exchange was a non-obligatory event in the life-cycle of the trypanosome. In
      addition, a preliminary analysis of the phenotype of procyclic stage trypanosomes
      derived from flies infected with two stocks, indicates that genetic exchange is
      unlikely to occur at this stage.

PMID- 1982634
TI  - Pharmacology of SK&F R-105058 and R-106114, N-ethyl carbamate ester prodrugs of
      fenoldopam.
AB  - The pharmacology of SK&F R-105058 and SK&F R-106114, N-ethyl carbamate ester
      prodrugs of fenoldopam, was evaluated in pentobarbital-anesthetized dogs. The
      selective dopamine 1 (DA1) antagonist, SCH 23390, significantly attenuated the
      renal vasodilator effects of SK&F R-82526, the active enantiomer of fenoldopam.
      This dose of SCH 23390 also significantly attenuated the increase in renal blood
      flow and decrease in renal vascular resistance induced by the administration of
      either SK&F R-106114 or SK&F R-105058. The cholinesterase inhibitor,
      physostigmine, at a dose that significantly enhanced the renal effects of
      acetylcholine, did not alter the in vivo renal vasodilator effects of SK&F R
      105058 or prevent conversion of SK&F R-105058 to fenoldopam. Thus, these data
      indicate that the renal vasodilator activity of fenoldopam prodrugs involves
      activation of DA1 receptors and that, unlike other carbamate ester prodrugs,
      conversion to the parent compound is unlikely to involve cholinesterase.

PMID- 1982635
TI  - The significance of the assays of urinary enzymes activity in patients with
      systemic lupus erythematosus.
AB  - The hyperexcretion of urinary enzymes with systemic Lupus Erythematosus (SLE) was
      assayed. 31 patients with confirmed SLE (30 women, and 1 man, age 16-33 years)
      were studied. Patients were divided into two groups according to the degree of
      kidney damage: 21 patients with proteinuria, and 10 patients without proteinuria.
      12 patients of the first group had nephrotic syndrome (NS). 30 practically
      healthy subjects served as a control group. In patients with Lupus-nephritis (LN)
      the increase of activities of urinary GGT, AP, BGRS, NAG, and CHE was observed,
      the increase was especially clearly shown in LN-patients with NS. The increase of
      activity of urinary GGT and NAG was shown in the group of SLE patients who did
      not have clinical and laboratory signs of LN, which can be used as early index
      for the damage of tubular epithelium.

PMID- 1982636
TI  - [Therapy with analgesics and anti-rheumatic agents in the aged].

PMID- 1982637
TI  - [Reduction of benzodiazepines. Group treatment positive with tapering off of
      tranquilizing agents].

PMID- 1982638
TI  - Strategies in genetic counseling: Reproductive genetics and new technologies.
      National Education Conference, 1990.

PMID- 1982640
TI  - Differential expression of drug resistance following in vitro exposure of human
      tumour cell lines to fractionated X-irradiation.
AB  - We have established that drug resistance can be expressed following in vitro
      exposure of tumour cells not only to antitumor drugs but also to fractionated X
      irradiation. These data therefore suggest a biological basis for the clinical
      problem of drug resistance that can occur in patients with previously irradiated
      tumors. These observations, if confirmed, have clinical implications for the
      combined modality approach and need to be considered when attempting to identify
      resistant tumour cells in clinical specimens with the aim of monitoring or
      identifying effective drug regimens.

PMID- 1982639
TI  - Mechanisms of multidrug resistance in human tumor cells. The roles of P
      glycoprotein, DNA topoisomerase II, and other factors.
AB  - Multidrug resistance (MDR) associated with overexpression of P-glycoprotein (Pgp)
      is a well-described experimental phenomenon that appears to have clinical
      correlates. However, recent descriptions of non-P-glycoprotein forms of MDR have
      complicated efforts to detect and circumvent MDR in the tumors of patients. One
      major form of natural product MDR appears to be due to alterations in the amount
      of activity of DNA topoisomerase II. Compared to Pgp-MDR cells, cells expressing
      this form of MDR (at-MDR) do not overexpress the mdr1 gene or its product, Pgp,
      are unaltered in drug accumulation and retention, are unaffected by such
      'modulators' of Pgp-MDR as verapamil, and express this phenotype recessively.
      Recently, other MDR cell lines have been described with some characteristics of
      Pgp-MDR (decreased drug accumulation and retention, increased drug cytotoxicity
      by modulators of MDR), but not others (no expression of the mdr1 gene or Pgp).
      Whether any non-Pgp forms of MDR occur in patients' tumors remains to be
      determined.

PMID- 1982641
TI  - Morphologic alterations in drug sensitive vs. drug resistant cells due to
      cytostatic application.

PMID- 1982642
TI  - Reversal of multidrug resistance.

PMID- 1982643
TI  - WHO Director-General announced new initiatives against cocaine at world drug
      summit.

PMID- 1982644
TI  - [Profile of patients with indications for orchidopexy during 1 year at the
      Pediatric Clinic in Olomouc].

PMID- 1982645
TI  - Synthesis and bioactivity of propranolol analogues with a rigid skeleton. I.
AB  - The synthesis of two kinds of propranolol analogues, A and B, with a rigid
      skeleton was investigated. The compounds were designed to help identify the
      conformation involved in beta-adrenergic receptor-propranolol interaction. The
      key intermediate, 2-hydroxy.2,3-dihydronaphtho[1,8-bc]pyran (5), was obtained
      starting from acenaphthenone (1). On sequential dehydration, hydroboration, and
      oxidation, 5 gave 2,3-dihydronaphtho[1,8-bc]pyran-3-one (8), which was converted
      to compound A. Compound 5 was also derived to 2-formyl-2,3-dihydronaphtho[1,8
      bc]pyran (13) via the 2-vinyl compound (12). Condensation of nitromethane with 13
      followed by reduction and alkylation produced the desired compound B. The beta
      blocking activities of A and B were examined.

PMID- 1982646
TI  - [Lymphocyte phenotypes and their correlation with clinical features in systemic
      lupus erythematosus (SLE)].
AB  - Lymphocyte phenotypes of peripheral blood from 32 SLE patients and 30 normal
      subjects were studied with 13 kinds of monoclonal antibodies using indirect
      immunofluorescence technique. The results showed that T4+, T8+, T3+ and T11+
      cells decreased in active cases of SLE, while Ia+, IL2R1+ and PCA-1+ cells
      increased, other B-cell phenotypes (B1, B2, B4, IgM, IgG, IgD) showed no
      significant difference from those of the normal group. Thus, in inactive SLE
      after therapeutic management, the numbers of T3+, T11+, T4+, Ia+ and IL2R1+ cells
      no longer show any abnormality, but the numbers of T8+, PCA-1+ cells and the
      level of serum IgG are still higher than normal. From the above-mentioned
      results, it was shown that: 1. The key change in active SLE is the abnormality of
      immunoregulatory T cells, especially T4+ cells; 2. In active SLE, some of the T
      cells have been activated in vivo and these immunocompetent cells play an
      important role in immunoglobulin production of B cells; 3. The hyperactivity of
      humoral immunity is mainly related to the increase of PCA-1+ cells under the
      regulation of T cells; 4. Both the lymphocyte phenotypes and clinical features of
      SLE showed heterogeneity.

PMID- 1982647
TI  - [Autologous peripheral hematopoietic stem cell transplantation in leukemia].
AB  - Six cases of acute leukemia patients were treated with APHSCT and the clinical
      results were satisfactory. The preparatory marrow ablative chemoradiotherapy
      regimen before APHSCT was same as that for autologous bone marrow transplantation
      (ABMT). The number of mononuclear cells infused to restore the hematopoietic
      function ranged from 1.65 to 2.92 x 10(8)/kg and these cells yielded 0.17 to 2.26
      x 10(4)/kg CFU-GM. The hematopoietic and immunological function of patients
      returned to normal level 25 to 38 days after APHSCT; the recovery was faster than
      that of ABMT and FLT. One patient each died of recurrence of leukemia and fungi
      septicemia 90 and 70 days after transplantation respectively, whereas the other
      four patients have survived for 9, 8, 4, and 2 months respectively.

PMID- 1982648
TI  - [Clinical study and immunological observation on potenlini treatment of epidemic
      hemorrhage fever].
AB  - 439 cases of epidemic hemorrhagic fever (EHF) in the febrile stage of the disease
      were randomly divided into two groups. 226 cases in therapeutic group were
      treated with daily intravenous drip of 60-100 ml potenlini for 3 days. Other
      measures of treatment in this group was just the same as those in the control
      group. The results showed that the duration of both the febrile stage and the
      hypotensive shock stage were shorter and the rate of recovering from hypotensive
      shock stage and oliguric stage in the therapeutic group (P less than 0.01) was
      higher as compared with the control group. BUN, ALT, urinary protein, white blood
      cells and platelets returned to normal level earlier than expected (P less than
      0.01). The occurrence rate of complication and case fatality rate in therapeutic
      group were lower. The research showed that potenlini in the treatment of EHF has
      effects. But it has not remarkable effects on immune adjustment.

PMID- 1982650
TI  - International symposium on urapidil. Proceedings of a satellite symposium
      entitled 'Multiple Action Antihypertensive Therapy with Special Reference to
      Alpha- and 5-HT-Receptors', Berlin, 16 June 1990.

PMID- 1982649
TI  - Pharmacological profile of antihypertensive drugs with serotonin receptor and
      alpha-adrenoceptor activity.
AB  - During the last few years, several antihypertensive drugs with multiple actions
      have been introduced. Most of these hybrid drugs are beta-adrenoceptor blockers
      with an additional vasodilator component, such as labetalol, dilevalol,
      carvedilol and celiprolol. A second category of antihypertensive drugs with
      multiple actions consists of agents which interact simultaneously with
      serotoninergic receptors and alpha-adrenoceptors. Urapidil, ketanserin, and a few
      experimental compounds related to these drugs are examples of this type of
      antihypertensive. They may be characterised pharmacologically as follows: (1)
      Ketanserin is a selective antagonist of serotonin 2 receptors with an additional
      much weaker alpha 1-adrenoceptor antagonistic activity. Its well documented
      antihypertensive activity cannot be explained by either serotonin 2-receptor
      blockade or alpha-adrenoceptor antagonism alone. An unknown type of interaction
      between serotonin 2-receptor and alpha 1-adrenoceptor blockade appears to be
      necessary, either in the periphery or in the CNS. (2) Urapidil is a selective
      alpha 1-adrenoceptor antagonist and, as such, a peripheral vasodilator. In
      addition, it displays central hypotensive activity, probably caused by the
      stimulation of serotonin 1A receptors in the CNS. This component is probably
      additive to the peripheral effect, and is also the background to the lack of
      reflex tachycardia seen with urapidil. The modes of action of both types of drugs
      are discussed in connection with the role of serotonin and its receptors in the
      cardiovascular system, both at the peripheral and the CNS levels.

PMID- 1982651
TI  - Effects of alpha-adrenoceptor antagonists on striated muscle microcirculation of
      conscious rats.

PMID- 1982652
TI  - Central and peripheral hypotensive activity of urapidil and its M1 and M2
      metabolites in the cat.

PMID- 1982653
TI  - Is blockade of alpha 1-adrenoceptors favourable in hypotension induced by
      stimulation of serotonin1A receptors in conscious dogs?

PMID- 1982654
TI  - Antihypertensive treatment with ketanserin shows no evidence of vascular
      serotonin2-receptor and alpha 1-adrenoceptor blockade.

PMID- 1982655
TI  - Aggravation of the severity of the clonidine withdrawal syndrome in conscious
      rats by beta 2-adrenoceptor antagonists.

PMID- 1982656
TI  - Behavioral, biochemical and neurotoxicological actions of the alpha-ethyl
      homologue of p-chloroamphetamine.
AB  - The present set of experiments was designed to examine the effects of extension
      of the alpha-methyl of p-chloroamphetamine (PCA) to an alpha-ethyl. Therefore,
      the alpha-ethyl homologue of PCA, 1-(4-chlorophenyl)-2-aminobutane (CAB), was
      compared to PCA in a number of pharmacological assays. CAB was 2-fold less potent
      than PCA at inhibiting synaptosomal uptake of [3H]5-hydroxytryptamine ([3H]5-HT),
      and 5-fold less potent at inhibiting uptake of [3H]dopamine ([3H]DA). In drug
      discrimination assays, CAB was approximately 3-fold less potent than PCA in
      animals trained to discriminate 3,4-methylenedioxymethamphetamine (MDMA) or its
      alpha-ethyl homologue, S-(+)-N-methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine (S
      (+)-MBDB), from saline. Monitoring with in vivo microdialysis, 10 mg/kg of PCA
      caused a large increase in extracellular DA and a significant decrease in 3,4
      dihydroxyphenylacetic acid (DOPAC) in the striatum. In contrast, 11 mg/kg CAB
      caused no increase and 22 mg/kg CAB caused only a slight increase in
      extracellular DA. Both doses of CAB caused a decrease in extracellular DOPAC. The
      potential 5-HT neurotoxicity of CAB was examined by measuring monoamine and
      metabolite levels and [3H]paroxetine binding at one week following acute doses. A
      10 mg/kg dose of PCA caused an 80% decrease in cortical and hippocampal
      serotonergic markers, while an equimolar dose of CAB decreased only hippocampal 5
      HT and 5-hydroxyindoleacetic acid (5-HIAA) levels. However, 22 mg/kg of CAB
      produced a 20-40% decrease in all serotonergic markers. Thus, extension of the
      alpha-alkyl significantly decreases the dopaminergic effects of PCA. The similar
      decrease in relative 5-HT neurotoxicity and the decreased ability to alter
      dopaminergic systems in vivo and in vitro supports the involvement of DA in the
      neurotoxicity of PCA.

PMID- 1982657
TI  - Effects of selective dopamine D1 and D2 receptor agonists on the rate of GABA
      synthesis in mouse brain.
AB  - The effects of dopamine D1 and D2 receptor agonists and antagonists on the rate
      of GABA synthesis in four regions of mouse brain (corpus striatum, cerebellum,
      cortex and hippocampus) were examined after irreversible inhibition of 4
      aminobutyrate: 2-oxoglutarate aminotransferase (EC 2.6.1.19; GABA-T) by
      gabaculine. The dopamine D2 receptor agonists PPHT, LY 171555 and RU 24213
      exerted a dose-related inhibitory effect on GABA synthesis in these four regions.
      The decreases in the rate of GABA formation were prevented by the dopamine D2
      receptor antagonist S(-)-sulpiride. The dopamine D1 receptor agonists SKF 77434
      and SKF 38393 augmented gabaculine-induced GABA accumulation in the corpus
      striatum only, and this effect was blocked by the dopamine D1 receptor antagonist
      SCH 23390. However, SKF 81297 and SKF 82958, two other dopamine D1 receptor
      agonists, did not affect or only marginally altered the rate of GABA synthesis.
      Stimulation of D2 receptors thus induces a decrease in the rate of GABA formation
      in the four brain areas examined, whereas stimulation of D1 receptors either
      increases GABA synthesis in the corpus striatum or does not alter it. This effect
      appears to be independent of the degree of receptor occupancy.

PMID- 1982658
TI  - Identification of alpha 2-adrenoceptors and non-adrenergic idazoxan binding sites
      in rabbit colon epithelial cells.
AB  - alpha 2-Adrenoceptors are possibly involved in the regulation of the
      hydroelectrolytic flux across the digestive mucosa. As no data are available
      concerning the existence of these receptors in colon epithelial cells, we aimed
      to investigate the existence of alpha 2-adrenoceptors in this tissue using
      tritiated antagonists. [3H]Yohimbine and [3H]rauwolscine were not usable to label
      colonic alpha 2-adrenoceptors because of their very high level of non-specific
      binding. In contrast, the methoxy derivative of idazoxan, [3H]RX821002, appeared
      a convenient radioligand for the purpose. [3H]RX821002 bound with high affinity
      (KD = 6.2 +/- 0.8 nM) to a single population of non-interacting sites (Bmax = 193
      +/- 17 fmol/mg protein). The rank order of potency of catecholamine enantiomers
      and adrenergic drugs to inhibit [3H]RX821002 binding demonstrated that the
      labelled sites are alpha 2-adrenoceptors and that 53% of the receptors are in a
      high-affinity state sensitive to GTP + NaCl. [3H]Idazoxan also bound to colocyte
      membranes, but inhibition by (-)-adrenaline and various imidazoline compounds
      indicated that this radioligands labels alpha 2-adrenoceptors and non-adrenergic
      sites. When experiments were performed under binding conditions impeding the
      interaction of [3H]idazoxan with the alpha 2-adrenoceptors (i.e. in presence of
      10(-4) M (-)-adrenaline), the Bmax of non-adrenergic idazoxan binding sites was
      97 +/- 8 fmol/mg protein and the KD was 3.5 +/- 0.5 nM. The sites were
      pharmacologically characterized with various imidazoline and non-imidazoline
      drugs. In order to study the putative relationship between alpha 2-adrenoceptors
      and non-adrenergic idazoxan binding sites, the expression of both kinds of sites
      was investigated along the crypt-to-surface axis. Crypt cells had a higher number
      of alpha 2-adrenoceptors than surface cells, whereas the number of non-adrenergic
      idazoxan binding sites remained constant. The results show that (i) alpha 2
      adrenoceptors coexist with non-adrenergic idazoxan binding sites in rabbit
      colocytes; (ii) the number of alpha 2-adrenoceptors is higher in crypt cells than
      in surface cells and (iii) alpha 2-adrenoceptors and non-adrenergic binding sites
      are different and unrelated.

PMID- 1982659
TI  - Binding of typical and atypical antipsychotics to 5-HT1C and 5-HT2 sites:
      clozapine potently interacts with 5-HT1C sites.
AB  - We determined the affinity of several typical and atypical antipsychotics for the
      5-HT1C and 5-HT2 sites using radioligand binding assays. Most of the
      antipsychotics tested appeared to bind to 5-HT2 sites with affinities that were
      fairly high (i.e. pKi values between 7 and 9) and significantly higher than for 5
      HT1C sites. In contrast, clozapine was found to have a significantly higher
      affinity for 5-HT1C than for 5-HT2 sites. Clozapine had the highest affinity for
      5-HT1C sites of all the compounds tested. These findings are consistent with the
      hypothesis that an interaction with 5-HT2 receptors may be relevant to the
      clinical activity of typical antipsychotics. The findings also suggest, however,
      that an interaction with 5-HT1C sites may be relevant to the mechanism of
      clinical action of clozapine and, perhaps, of other atypical antipsychotics.

PMID- 1982660
TI  - Mosquito fauna of medical importance in Kumbakkarai: a tourist spot near Madurai
      (Tamil Nadu).

PMID- 1982661
TI  - Omeprazole and acid inhibition: the essential issues. Proceedings of a symposium.
      London, April 1990.

PMID- 1982662
TI  - Treatment of acid-related disorders with gastric acid inhibitors: the state of
      the art.
AB  - Since their introduction in 1976, and until recently, the H2-receptor antagonists
      have been the 'state-of-the-art' gastric acid inhibitors, but the advent of
      omeprazole, the acid pump inhibitor, has necessitated a reassessment of therapy
      for acid-related diseases. In making this reassessment, the following therapeutic
      goals should be considered: rapid and reliable therapeutic effect, safety, simple
      treatment regimen, resolution of recurrence, and cost-effectiveness. Extensive
      clinical evidence indicates that omeprazole offers an advance over the H2
      receptor antagonists in achieving these goals. A series of meta-analyses shows
      that omeprazole gives more rapid symptom relief and more reliable healing than H2
      receptor antagonist, ranitidine, in uncomplicated duodenal ulcer (DU), in
      uncomplicated gastric ulcer (GU) and in reflux oesophagitis (RO). By contrast
      with the H2-receptor antagonists, refractoriness leading to failure to heal is
      virtually unknown with omeprazole. Omeprazole also fulfils the goal of
      therapeutic safety, and this has been documented in extensive short- and long
      term clinical and laboratory studies. Omeprazole has a simple treatment regimen:
      20 mg once daily is recommended in the routine treatment of DU, GU and RO. As a
      result of its high therapeutic success rate, omeprazole is also cost-effective.
      Taking all these factors into account, it is concluded that omeprazole approaches
      the therapeutic targets set for the treatment of acid-related disorders.

PMID- 1982663
TI  - [Dynamics of mental work capacity of 10th-grade students during the school year].

PMID- 1982664
TI  - Effect of serotonergic agents on neuroleptic induced catalepsy in rats.
AB  - Three pharmacological tools namely zimelidine, danitracen and MK 212, were
      selected to examine the nature of involvement of serotonergic neurotransmission
      in catalepsy, an undesirable side effect following administration of neuroleptics
      in rats. Reserpine and haloperidol were chosen as cataleptogenic challenges.
      Zimelidine, a serotonin (5-HT) reuptake blocker, inhibited the manifestation of
      reserpine and haloperidol induced catalepsy. However, a dose dependent effect
      could not be demonstrated beyond 30 mumoles/kg. Danitracen, a 5-HT receptor
      blocker, prevented the occurrence of the symptoms that were observed following
      reserpine treatment but it could not elicit blockade of haloperidol response. MK
      212, an S2 (5-HT2) receptor stimulant forestalled the occurrence of reserpine
      syndrome at lower doses but exhibited cataleptogenic effects at higher doses.
      Besides, MK 212 failed to influence catalepsy following administration of
      haloperidol. It appears that 5-HT exerts a homoeostatic control in the regulatory
      neuraxis in neuroleptic induced neurological side effects.

PMID- 1982665
TI  - Edentulousness and neuroleptic-induced neck and trunk dyskinesia.
AB  - Edentulousness, by disrupting trigeminal propioceptive input from the oral cavity
      to the basal ganglia, may increase the risk for neuroleptic-induced orofacial
      dyskinesia. Since lesions of the globus pallidus alter trigeminal sensory-induced
      reflexive neck muscle activity in rats and the putamen-caudate complex regulates
      vestibular and propioceptive mechanisms, edentulousness could facilitate also the
      expression of neuroleptic-induced neck and trunk dyskinesias. In a sample of 131
      neuroleptic-treated chronic schizophrenic patients, we found that edentulous
      patients exhibited significantly more neck and trunk dyskinesias as compared to
      nonedentulous patients (p less than 005). By contrast, dyskinesias of the face,
      tongue, and extremities did not differ between the two cohorts of patients. Our
      findings imply that edentulousness may increase the risk of neck and trunk
      dyskinesias and highlight the importance of the dental status in tardive
      dyskinesia.

PMID- 1982666
TI  - [Evaluation of T cell subsets in myasthenia gravis by anti-T cell monoclonal
      antibodies].
AB  - In this paper, T lymphocyte subsets were measured in the peripheral blood of 46
      patients with myasthenia gravis (MG) and 86 healthy controls, by using a modified
      microcytotoxicity assay and OKT monoclonal antibodies. The results showed that
      the OKT+3, OKT+4, OKT+8 cells of the patients with MG decreased significantly as
      compared with those of the controls (57.71% versus 66.42%; 34.50% versus 41.65%;
      21.23% versus 27.19% respectively, P less than 0.01), and the OKT4/OKT8 ratio
      increased significantly (2.19 versus 1.64, P less than 0.05). Furthermore, the
      patients with the ocular type had less OKT+8 cells than those with the general
      type (14.19% versus 23.47%, P less than 0.05 and had a high OKT4/OKT8 ratio (3.27
      versus 1.57, P less than 0.01). No correlating changes of T cell subsets with
      clinical conditions in that age, sex, and severity showed, and also that there
      was no difference between the patients whether prednisone was used or not (P
      greater than 0.05).

PMID- 1982667
TI  - Responses of rat isolated intestinal segments to stimulation of perivascular
      mesenteric nerve fibres.
AB  - 1. Isolated preparations of segments of rat jejunum were set up for isotonic
      recording of the activity of the longitudinal smooth muscle and the extrinsic
      nerve supply running with the mesenteric blood vessels was stimulated for 30-s
      periods at 0.5-20 Hz. 2. Contractions were regularly elicited during periods of
      stimulation at 0.5-2 Hz, and were usually elicited during stimulation at 5 Hz,
      but relaxations were usually elicited during stimulation at 10 and 20 Hz. On
      cessation of the period of stimulation, a secondary contraction occurred in most
      preparations regardless of whether the primary response during the period of
      stimulation had been a contraction or a relaxation. 3. Tetrodotoxin (0.9 microM)
      abolished responses during periods of stimulation and the secondary contraction.
      4. The relaxations were mimicked by noradrenaline and were abolished by blockade
      of alpha- plus beta-adrenoceptors but were not affected by hexamethonium,
      indicating that they are attributable to stimulation of postganglionic
      noradrenergic fibres. 5. The contractions were mimicked by acetylcholine and were
      abolished by atropine and hexamethonium, suggesting that they are attributable to
      stimulation of preganglionic cholinergic nerves: they were also abolished in the
      presence of capsaicin, indicating that sensory neuropeptide-containing nerve
      fibres may be involved. 6. The secondary contraction that usually occurred on
      cessation of stimulation was still present after blockade by atropine or
      capsaicin of the contractions occurring during stimulation. It was also present
      after blockade by propranolol and phentolamine of the relaxations occurring
      during stimulation, and was not affected by indomethacin.

PMID- 1982668
TI  - Effects of bromoacetylalprenololmenthane (BAAM), an irreversible beta
      adrenoceptor antagonist, on the rat isolated left atria and portal vein.
AB  - 1. The effects of treatment with bromoacetylalprenololmenthane (BAAM), an
      irreversible beta-adrenoceptor antagonist, for 30 min on the contractile
      responses of the rat left atria and portal vein have been determined. 2. On the
      electrically driven rat left atria, BAAM at 10(-5) M followed by a 60-min wash
      out caused parallel rightward shifts of the isoprenaline response curves with no
      reduction in the maximal response to isoprenaline. 3. Treatment of the atria with
      BAAM at 3 x 10(-5) M caused non-parallel rightward shifts of isoprenaline
      response curves with a reduction in the maximum response to isoprenaline. The KA
      (dissociation constant) for isoprenaline at beta 1-adrenoceptors was 7.3 x 10(-7)
      M. Calculation of receptor occupancy demonstrated that in order to produce a
      maximal response of the rat left atria, isoprenaline had to occupy 12% of the
      beta 1-adrenoceptors. 4. Treatment of the atria with higher concentrations of
      BAAM (greater than or equal to 6 x 10(-5) M) caused a non-specific action, the
      reduction of the response to electrical stimulation. 5. On the rat portal vein,
      BAAM at 3 x 10(-7)-3 x 10(-6) M followed by a 45-min wash-out had no effect on
      the spontaneous contractile activity, caused non-parallel rightward shifts of
      isoprenaline response curves with a depression of the isoprenaline maximum
      responses. Using data derived from experiments with 3 x 10(-7), 10(-6) and 3 x
      10(-6) M BAAM, the KA for isoprenaline at beta 2-adrenoceptor was 6.4, 3.7 and
      7.7 x 10(-7) M and the calculated receptor occupancy was that in order to produce
      a maximal response of the rat portal vein, isoprenaline had to occupy 14, 21 and
      12%, respectively of the beta 2-adrenoceptors. 6. The present study with the rat
      left atria and portal vein has shown that it is possible to determine treatments
      with BAAM that produce no non-specific actions and consequently BAAM may be used
      as an experimental tool in KA and receptor occupancy determinations in these
      tissues.

PMID- 1982669
TI  - Effects of pregnancy and endothelial cell removal on alpha-adrenoceptor-mediated
      responses of rat thoracic aortae.
AB  - 1. The possibility was examined that changes in sensitivity of the aorta to alpha
      adrenoceptor agonists during pregnancy in the rat are due to changes in smooth
      muscle receptor-mediated responses and/or endothelial cell-mediated responses. 2.
      Maximum constrictor responses to phenylephrine (PE) of both endothelium-intact
      and denuded thoracic aortic rings were greater when tissues were obtained from 20
      day pregnant rats compared with non-pregnant ones. For endothelium-denuded
      thoracic aortic rings, the pA2 value for phentolamine as an antagonist of PE was
      not significantly different for rings from 20-day pregnant rats compared with
      rings from non-pregnant rats. 3. Prazosin (1-50 nM) markedly depressed maximum
      contractile responses to PE of endothelium-intact (but not denuded) thoracic
      aortic rings from both non-pregnant and 20-day pregnant rats. However, this
      marked depression of maximum responses by prazosin did not occur in the
      additional presence of yohimbine (10 nM), and yohimbine alone (10-500 mM) did not
      affect maximum responses to PE. There was no significant difference between the
      pA2 value for prazosin against PE-induced contractions of endothelium-denuded
      aortic rings obtained from either non-pregnant or 20-day pregnant rats (in the
      presence of yohimbine, 10 nM). 4. These results provide no evidence for a change
      in aortic smooth muscle alpha-adrenoceptor affinity during pregnancy, although
      maximum responsiveness of aortic smooth muscle to PE is increased on day 20 of
      pregnancy (c.f. non-pregnant controls).

PMID- 1982671
TI  - Liver regeneration after partial hepatectomy: effects of glucose and branched
      chain amino acid.
AB  - The phenomenon of liver regeneration has been observed within several days after
      partial hepatectomy, though there is still much controversy as to its initiation,
      regulation, and the control factors behind it. Male Wistar rats weighing around
      200 g were used as subjects in this study. Partial hepatectomy with resection of
      the median and left lateral lobes (67.31%) was performed. High glucose, low
      glucose, or high or low branched-chain amino acid (BCAA) solutions were given
      intravenously 2 days prior to the partial hepatectomy. The rats were sacrificed
      at 6, 24, 48, and 72 hours after the operation. Remnant liver weight,
      Deoxyribonucleic acid (DNA) content, DNA synthesis rate, and mitotic index were
      chosen as markers for comparing the effects of the glucose and branched-chain
      amino acid solutions on liver regeneration. The results were as follows: (1)
      following removal of two-thirds of a rat's liver, DNA synthesis increased
      abruptly, peaking at 24 hours, the mitotic index reached a maximum at 48 hours,
      and the remaining lobes had doubled in size by 48 hours and had attained around
      90% of the normal liver weight at 72 hours; (2) judging by the results of the
      remnant liver weight, DNA content, and DNA synthesis rate, the low glucose
      infusion rates showed the worst regenerative condition; and (3) the only effect
      of BCAA on liver regeneration observed was that low BCAA infusion rates resulted
      in a lower DNA content in the remnant liver.

PMID- 1982670
TI  - Gut regulatory peptides and pancreatic beta-cell response to nutritional stimuli
      in the elderly.
AB  - Pancreatic beta-cell and gut regulatory peptide responses were investigated in 13
      healthy elderly and 12 young subjects (control group) after a standard meal test.
      In addition to hyperinsulinemia and hypergastrinemia, we found lower basal and
      postprandial total integrated responses (TIR) for gastric inhibitory polypeptide
      and bombesin in the elderly group. The mean postprandial TIR for neurotensin (NT)
      was significantly higher in the aged subjects, but the somatostatin response was
      suppressed in this group.

PMID- 1982672
TI  - Diurnal variation in water, sodium and potassium excretion in primary
      glomerulonephritic patients and its relation to diurnal kallikrein excretion.
AB  - In order to investigate whether or not primary glomerulonephritic patients have
      abnormal diurnal water, sodium, and potassium excretion and its relation to
      diurnal urinary kallikrein excretion (UKE)., we studied the diurnal patterns of
      urinary water, sodium, potassium, and kallikrein excretion in 16 primary
      glomerulonephritic patients and 12 normal persons. Urinary kallikrein activity
      was measured by the enzymatic hydrolysis of synthetic chromogenic substrate S
      2266, and urinary electrolytes were measured by flame photometry. The day, night,
      and 24-hour urine outputs were significantly higher in glomerulonephritic
      patients, but urinary sodium, potassium and kallikrein excretion at all periods
      of collection did not differ between glomerulonephritic patients and normal
      controls. UKE was positively correlated with urinary potassium excretion in both
      normal controls (r = 0.5, p less than 0.05) and glomerulonephritic patients (r =
      0.66, p less than 0.01), whereas no correlation existed between UKE and urinary
      water excretion, or UKE and urinary sodium excretion in either group. The
      day/night output ratio of water, sodium and potassium excretion were not
      different between glomerulonephritic patients and normal subjects. These results
      indicate that: (1) there is no abnormal diurnal water, sodium, potassium, and
      kallikrein excretion in primary glomerulonephritic patients with fair renal
      function; and (2) urinary kallikrein may play a role in the regulation of urinary
      potassium excretion.

PMID- 1982673
TI  - Sonographic presentation in autoimmune thyroiditis.
AB  - We used real-time ultrasonography to examine 60 patients with autoimmune
      thyroiditis, then correlated the ultrasonic pictures with thyroid function,
      thyroid autoantibodies and fine needle aspiration cytology. In these 60 patients,
      45 (75%) showed diffuse goiter, 6 (10%) showed multinodular goiter, and 9 (15%)
      had a solitary thyroid nodule sonographically. One of the 9 patients with a
      solitary nodule was a case of autoimmune thyroiditis combined with papillary
      carcinoma. The echogenicity of the thyroid was more than, the same as, or less
      than that of the adjacent muscles in 17, 22, and 21 patients, respectively. The
      groups were classified as hyperechoic, isoechoic, and hypoechoic, respectively.
      The mean serum T4 level was significantly lower in the hypoechoic group than in
      the hyperechoic or isoechoic groups (p less than 0.01 and p less than 0.05,
      respectively), and the incidence of hypothyroidism was significantly higher in
      the hypoechoic group than in the hyperechoic or isoechoic groups (p less than
      0.001 and p less than 0.005, respectively). In addition, high titers of the
      antithyroid microsomal antibody (greater than or equal to 1280) were present more
      frequently in the hypoechoic group than in the hyperechoic or isoechoic groups (p
      less than 0.01 and p less than 0.05, respectively). There was no significant
      correlation between the cytomorphology and echogenicity of the thyroid in these
      cases. We conclude that sonography has two major uses in evaluating autoimmune
      thyroiditis: First, it is useful in excluding the coexistence of thyroid nodules;
      and second, marked hypoechogenicity of the thyroid implies an active cytotoxic
      autoimmune process and possibly a hypothyroid state.

PMID- 1982674
TI  - Computed tomography in the evaluation of pleural dissemination in lung cancer.
AB  - A total of 19 patients with lung cancer were recognized as unresectable or not
      curatively resectable at thoracotomy due to pleural dissemination during the
      period from January 1984 to March 1989. The computed tomography films of these
      cases were reviewed retrospectively to search for clues of early detection of
      pleural dissemination in order to avoid unnecessary exploration. The findings of
      the pleura in these 19 patients included: fine pleural nodules in 12 cases,
      pleural thickening in 11, pleural surface irregularity in 10, direct pleural
      attachment of the tumor in 8, pleural retraction by the tumor in 7, pleural
      effusion in 5, and chest wall invasion in 5. In this series, 15 out of the 19
      cases had at least one of the following three findings: pleural thickening,
      pleural surface irregularity or pleural nodules. These pleural changes on a chest
      CT should raise the suspicion of pleural dissemination. An additional diagnostic
      procedure to establish diagnosis before exploration is suggested.

PMID- 1982675
TI  - Laser nephelometric quantitation of protein in urine and cerebrospinal fluid.
AB  - We describe a rapid method for the routine determination of protein in
      cerebrospinal fluid (CSF) and in urine using laser nephelometer. The relative
      light scattering (RLS) resulting from the interaction of trichloroacetic acid
      (TCA) and protein is linearly related to the concentration of protein from 0.01
      to 6.0 g/L. Precision studies indicate that the day-to-day coefficient of
      variation (CV) for two CSF controls (0.32 and 0.64 g/L) were 6.4% and 4.9%,
      respectively. The day-to-day CV's for two urine controls (0.39 and 0.84 g/L) were
      5.8% and 2.9%, respectively. Correlation studies with a manual
      spectroturbidimetric method revealed a correlation coefficient of 0.99 for both
      CSF and urine specimens. The proposed method, which uses a smaller sample size,
      is fast and provides greater sensitivity at low ranges due to the ability to
      increase the sensitivity by the laser nephelometer.

PMID- 1982676
TI  - Breath hydrogen test for assessment of lactose malabsorption following rotavirus
      gastroenteritis.
AB  - Ninety infants and young children with acute gastroenteritis were investigated
      for lactose malabsorption. Each of them was given an oral lactose load of 2g per
      kg of body weight after which breath hydrogen excretion was measured, and each
      was observed for clinical symptoms of lactose intolerance. Only 2 patients, given
      2g per kg of lactose, had clinical lactose intolerance. Forty-nine of the 90
      patients studied were found to have the rotavirus antigen in their stools. Forty
      five of them were found to have an abnormal lactose breath hydrogen test (LBHT).
      Twenty-three patients with abnormal LBHT were restarted on a diluted lactose
      containing formula for oral feeding. They required longer hospitalization (mean
      6.7 days, range 3-14 days) and were free of diarrhea in 14 days (mean 7.5 days).
      Twenty-two patients found to have an abnormal LBHT were given a nonlactose
      containing formula (Isomil, Nursoy, Alsoy, ProSobee, or Bebelac FL) when
      restarted on oral feeding. All patients require less than 5 days of
      hospitalization and free of diarrhea in 5 days (mean 3.4 days). The difference
      was statistically significant (p less than 0.05).

PMID- 1982677
TI  - The role of continuous passive motion following total knee arthroplasty.
AB  - A retrospective review of 25 knees with postoperative continuous passive motion
      (CPM) treatment following total knee arthroplasty (TKA) was compared with a
      control group of 25 knees without postoperative CPM. The diagnoses were similar
      in both groups, with osteoarthritis in 43 knees, traumatic arthritis in 2 knees,
      rheumatoid arthritis in 2 knees, osteonecrosis in one knee, and gouty arthritis
      in one knee. Average knee flexion at discharge was 93.2 degrees in the CPM group
      and 86.5 degrees in the control group (p less than 0.01). Eighty percent of the
      CPM group and 64% of the control group had achieved 90 degrees of flexion before
      hospital discharge. The time required to achieve 90 degrees of flexion after TKA
      averaged 9.6 days in the CPM group and 11 days in the control group (p less than
      0.01). There was no significant difference in flexion at 3 months or at 1 year
      postoperatively between the two groups. The duration of hospitalization was not
      significantly different between the two groups. One knee in the CPM group and 3
      knees in the control group required manipulation. Wound hemovac drainage and
      transfusion requirements were not significantly different. The number of pain
      medication was not significantly different between the two groups. The CPM made
      the TKA knee achieve motion earlier with fewer complications.

PMID- 1982678
TI  - Reliability and validity of using a Brief Psychiatric Symptom Rating Scale in
      clinical practice.
AB  - To develop a reliable and valid psychiatric self-rating scale for use in medical
      practice, the authors modified Derogatis' Symptom Check List-90-R (SCL-90-R) and
      designed a shorter form, named Brief Symptom Rating Scale (BSRS). The BSRS
      comprises 50 items, which best reflect the original ten symptom dimensions and
      three indices of psychopathology from the SCL-90-R. The BSRS has been proven in
      different populations to have an excellent split-half reliability as well as good
      internal structure according to factor analysis. In addition, BSRS scores are
      highly correlated with the parental form SCL-90-R among medical populations for
      each symptom dimension and the three indices. The rate of accurate classification
      for BSRS between psychiatric and nonpsychiatric cases was 75.8%, with a
      sensitivity of 66.7% and a specificity of 86.7% by discriminant analysis based on
      10 dimensional scores obtained from 1,638 subjects, randomly selected from the
      Psychiatric Outpatient Clinic, the Family Medicine Clinic and nonpsychiatric
      medical inpatients. Therefore, the BSRS is a satisfactory global measure and case
      finding screening instrument for psychopathology in both psychiatric and
      nonpsychiatric medical settings.

PMID- 1982679
TI  - Aortomesenteric bypass using autogenous saphenous vein graft for superior
      mensenteric artery aneurysm: report of a case.
AB  - We report a 62-year-old man who had symptoms of abdominal angina and was
      diagnosed preoperatively with a superior mesenteric artery (SMA) aneurysm. The
      findings of the CT scan and angiography revealed a 3 X 4 cm saccular aneurysm at
      the proximal site of the SMA. During abdominal exploration, a weak pulsation of
      the SMA branches distal to the aneurysm was felt. The aneurysmal cavity was full
      of old thrombi. Brisk retrograde bleeding from the orifices of the connecting
      collaterals was seen after removal of the thrombi. Our operative procedures
      included endoaneurysmorrhaphy, proximal ligation, and distal interruption of the
      aneurysm. Vascular reconstruction by an aortomesenteric bypass using a segment of
      autogenous saphenous vein graft was also done. After creating the vein graft
      bypass, the weak pulsation of the distal SMA branches became normalized. The
      patient enjoyed an uneventful postoperative course and did not complain of
      abdominal pain on clinical follow up. Four months later, he received an
      evaluation including angiography and CT scan, which confirmed that the vein graft
      was patent and without deformity.

PMID- 1982680
TI  - Common carotid artery dissection diagnosed by ultrasonic image: report of a case.
AB  - Carotid artery dissection is not uncommon and usually starts at the internal
      carotid artery. It rarely begins in the common carotid artery. It may cause
      symptoms of cerebral vascular insufficiency such as stroke and transient ischemic
      attacks. The case reported here is a 38-year-old man with an acute onset of left
      hemiparesis 2 hours after drinking three bottles of beer. Computed tomographic
      scan showed cerebral infarction in the territory of the right middle and anterior
      cerebral arteries. Ultrasonic imagings showed an intimal flap, starting at the
      bifurcation of the right common carotid artery, indicative of arterial
      dissection. Angiography confirmed the diagnosis and the arterial dissection
      appeared to extend into and terminate at the internal carotid artery.

PMID- 1982681
TI  - Pulmonary mucormycosis: the first case with preoperative diagnosis and successful
      surgical treatment in Taiwan.
AB  - Pulmonarycosis is a rare disease, which refers to an infection by fungi belonging
      to the order Mucorales. This organism usually invades the skin, nose mouth,
      paranasal sinus, gastrointestinal tract, lung, brain, eyes and so forth. It
      usually occurs in patients with diabetes mellitus, hematological malignancy or
      other immunocompromised states. Until recently, this disease was rarely diagnosed
      before death. We report a case of pulmonary mucormycosis in a woman with poorly
      controlled diabetes mellitus. This is the first case in Taiwan of pulmonary
      mucormycosis diagnosed preoperatively and treated successfully by lobectomy only.
      Persistent pulmonary lesions resistant to antibiotic treatment in high risk
      patients should arouse the suspicion of mucormycosis. Prompt bronchoscopic
      examination, open lung biopsy and transthoracic pulmonary aspiration cytology and
      biopsy should be done. Surgical resection of localized lesions remains the
      treatment of choice.

PMID- 1982682
TI  - Minimal change myopathy: report of a case.
AB  - A young boy, aged 5 years 7 months, presented with generalized hypotonia and
      proximal muscle weakness, and had exhibited delayed motor milestones since birth,
      He showed talipes planovalgus, a myopathic face, nasal tone vocalization,
      positive Gowers' sign and decreased tendon reflexes, but there was no
      intellectual impairment or seizure. The serum creatine kinase level and
      peripheral nerve conduction velocity, as well as the electromyogram and
      electrocardiogram, were within normal limits. A biopsy specimen from the left
      biceps brachii muscle revealed minimal nonspecific changes and mild variations in
      fiber size with an increased number of undifferentiated type 2C fibers, but no
      subcellular abnormalities were found on either the histochemical or electron
      microscopic examinations. The patient was diagnosed as having minimal change
      myopathy and improved clinically in muscle strength after one year of follow-up.

PMID- 1982683
TI  - Placenta increta in the second trimester of pregnancy: report of a case.
AB  - A rare case of placenta increta in the second trimester of pregnancy is reported.
      The patient was at 15 weeks gestation when the pregnancy, which had been
      complicated by a maternal rubella infection, was terminated at a regional
      hospital. However, vaginal bleeding persisted after the operation in spite of
      medication to control bleeding. Curettage of the uterine cavity one month later
      failed to reveal any retained placental tissue or other pathology. Therefore, an
      exploratory laparotomy was performed, yet nothing particular was found in the
      peritoneal cavity. So, the patient was transferred to our department. Sonography
      revealed a lower uterine mass of 4.0 x 3.3 cm in size. A persistently low serum
      hCG titer was also found. Placenta accreta was highly suspected. Three doses of
      methotrexate were given to control bleeding, yet without results. Hysterectomy
      was finally performed. A histological study revealed placenta increta.

PMID- 1982684
TI  - Conservative treatment for prostatorectal or urethrorectal perforation during
      transurethral surgical procedures.
AB  - From 7 March 1989 to 16 December 1989, we experienced 2 prostatorectal and 2
      urethrorectal perforations during transurethral surgical procedures at the
      National Taiwan University Hospital (3 cases) and Tz'u-Chi General Hospital (1
      case). All 4 patients were men. Their ages ranged from 57 to 76 years with a mean
      of 66 years. All 4 complications were identified immediately. Neither a
      transrectal/suprapubic immediate (or staged) direct suturing, nor a
      colostomy/cystostomy was needed in our series. Instead, we introduced a rectal
      tube coated with gauze soaked in Betadine and vaseline, which fit tightly into
      the rectum for an average of 4 days (range from 3 to 5 days). A 22-Fr three-way
      indwelling Foley catheter with continuous normal saline irrigation was also
      applied for 7 to 14 days (9.5 days on average). Nothing by mouth started
      immediately after the operation (range from 3 to 7 days; 5.3 days on average).
      All 4 patients were discharged in good condition with a mean postoperative stay
      of 14 days (range from 11 to 18 days). No prostatorectal or urethrorectal fistula
      were found during an average follow-up period of 13.5 months (range from 10 to 17
      months).

PMID- 1982685
TI  - Pyeloduodenal fistula: report of 2 cases.
AB  - Pyeloduodenal fistula is a rare event, which can occur spontaneously or be caused
      by trauma. We present two such cases, of which, one was complicated by
      percutaneous nephrolithotomy for a right renal stone and the other occurred
      spontaneously from right renal and perirenal abscesses. Its etiology,
      pathogenesis, clinical manifestations, diagnosis and treatment are discussed. We
      emphasize that with the increasing use of interventional uroradiologic
      procedures, particularly percutaneous nephrolithotomy, we may encounter more
      traumatic pyeloduodenal fistulae.

PMID- 1982686
TI  - Fanconi syndrome: report of a case.
AB  - A 59-year-old female patient was admitted because of muscle weakness in all four
      limbs for a period of 5 days. She had been found to have Graves' disease 4 years
      ago previous to this, and had received a subtotal thyroidectomy 1 year later.
      Hypothyroidism supervened and she had been receiving levothyroxine replacement in
      recent years. She also had non-insulin-dependent diabetes, which was controlled
      with diet only. During the 5 days prior to admission, she developed muscle
      weakness which finally worsened to complete paralysis of all four limbs. Physical
      examination showed tenderness and weakness of the extremity muscles. Abnormal
      laboratory data included serum K, 1.6 mEq/L; P, 1.2 mg/dl; uric acid, 1.6 mg/dl;
      fasting glucose, 267 mg/dl; T3, 36.65 ng/dl; T4, 4.0 micrograms/dl; TSH, 5.35 mu
      u/ml; free T4, 0.57 ng/dl; and metabolic acidosis with pH, 7.298; PCO2, 27.0
      mmHg; and HCO3, 12.8 mEq/L. An EKG showed a prominent U wave, and urinalysis
      revealed renal glucosuria and massive aminoaciduria. An oral sodium bicarbonate
      loading test showed an increasing loss of bicarbonate through the urine, while
      the plasma bicarbonate level was elevated. Clinical manifestations improved after
      the administration of sodium bicarbonate, potassium chloride and neutral
      phosphate.

PMID- 1982688
TI  - [A survey on the appropriateness of the Medical Care Act].

PMID- 1982687
TI  - [Gallium-67 lung scanning in pulmonary tuberculosis].

PMID- 1982689
TI  - Abstracts of the Sixth World Congress on Pain. Adelaide, Australia, 1-6 April
      1990.

PMID- 1982690
TI  - Effects of low doses of neuroleptics on temporal regulation in a differential
      reinforcement of response duration (DRRD) schedule in the dog.
AB  - It has been shown that low doses of neuroleptics could disinhibit behaviour in
      animals as well as in man. This study aims to measure the effects of low doses of
      haloperidol (0.01, 0.05, 0.1 mg/kg) and sulpiride (5, 10, 15 mg/kg) in the dog
      using a differential reinforcement of response duration (DRRD) schedule with
      positive and negative external stimuli. Together with a decrease in response
      rate, a leftward shift in the temporal distribution of response duration is
      measured. These results are discussed in terms of a deregulation of the internal
      clock, a lessening in the ability to wait for the reward, a reduction in the
      frustration of not obtaining reinforcements when errors are made and an increase
      in the sensibility to reinforcement through appetite stimulation or decrease in
      the satiety level.

PMID- 1982691
TI  - The hypothyroid rat as a model of increased sensitivity to dopamine receptor
      agonists.
AB  - Control and hypothyroid rats were challenged with a range of doses (0.5-4
      mumol/kg) of either the nonselective dopamine agonist, apomorphine, or the
      selective D2 receptor agonist. LY 171555, and their stereotyped head-down
      sniffing (SHDS) responses measured. The dose-response curves for both agonists
      were shifted to the left in the hypothyroid rats compared to water-treated
      controls. Increasing doses of the selective D2 antagonist, raclopride, caused a
      parallel shift to the right in the LY 171555-induced SHDS dose-response curve.
      Schild analysis revealed a decreased sensitivity to raclopride in the hypothyroid
      animals. The selective D1 antagonist SCH 23390 was observed to decrease the
      maximal response elicited by LY 171555 in a dose-dependent manner and the
      hypothyroid rats were more sensitive to this effect. It was concluded that
      hypothyroid rats showed an apparent increased sensitivity to D2 receptor agonists
      and a decreased sensitivity to D2 antagonists. In addition, the facilitation
      effect of the D1 receptor on the D2 receptor appeared less tightly coupled in the
      hypothyroid rats.

PMID- 1982692
TI  - Methylenedioxymethamphetamine's capacity to establish place preferences and
      modify intake of an alcoholic beverage.
AB  - Doses of 0.2, 2.0, 6.3 and 20.0 mg/kg 3,4-methylenedioxymethamphetamine (MDMA), a
      putative neurotoxin at serotonergic neurons and a recreational drug, were
      assessed using Sprague-Dawley rats in the conditioned place preference (CPP)
      test. Also, the drug's effects on intake of a sweetened ethanol solution (ES) was
      assessed. The CP testing involved multiple administrations of MDMA with frequent
      periodic testing (weekly for 4 weeks) of MDMA's effects. Doses of 2.0 and 6.3
      mg/kg produced positive CPPs with every test. MDMA also affected rats' gain in
      body weight across the 4 weeks of dosing. The 2.0 mg/kg reliably incremented gain
      in body weight, while the 20.0 mg/kg dose reliably attenuated it. In the drinking
      experiment, water-deprived rats (22 h/day) were given daily opportunities to
      drink either tap water or a sweetened ES. When stable intakes were achieved,
      MDMA's effects were assessed across repeated daily administrations (12 days) and
      subsequently (16 days). MDMA, dose-relatedly, decreased intake of both ES and
      water with the highest dose leading to marked loss in body weight. Intakes of
      fluids were not modified markedly subsequent to dosing. In summary, MDMA is an
      agent that produces a positive CPP (providing further evidence for MDMA's abuse
      liability), produces changes in weight gain and nonselectively reduces fluid
      intake among fluid-deprived rats.

PMID- 1982693
TI  - The effect of LHRH on rat conditioned avoidance behavior: interaction with brain
      catecholamines.
AB  - LHRH (100 micrograms/kg. SC) impairs the acquisition of two-way avoidance
      conditioning. This is partially potentiated by pretreatment with alpha
      methyltyrosine (alpha-MT; 250 mg/kg IP) or fusaric acid (10 mg/kg IP). L-DOPA
      (100 mg/kg IP) administered 5 h after alpha-MT partially reversed its effects.
      The possible roles of brain catecholamines on the behavioral effects of LHRH are
      analysed. Other tentative mechanisms of action are also discussed.

PMID- 1982694
TI  - The influence of conditioned fear-induced stress on the opioid systems in the
      rat.
AB  - In this study the rats were repeatedly placed in a conditioning box, and 30 min
      later were subjected to a mild foot-shock. Anticipation of painful stimuli
      resulted in development of antinociception before a painful stimulus was applied.
      This conditioned fear-induced antinociception was antagonized by naloxone (1
      mg/kg IP), as well as by ipsapirone (10 mg/kg IP), as measured by a tail-flick
      test. Stressed rats were hypersensitive to the analgesic action of morphine (1
      mg/kg SC), but not to the specific kappa agonist U69,593 (0.1 mg/kg SC). In order
      to determine the involvement of the proopiomelanocortin and prodynorphin systems
      in stress we measured levels of their represenative peptides beta-endorphin and
      alpha-neoendorphin using selective RIAs. Biochemical data showed that conditioned
      stress evoked a marked decrease in the beta-endorphin level in the hypothalamus
      and both lobes of the pituitary, together with a three-fold increase in the
      peptide level in the plasma. In contrast, the level of alpha-neoendorphin in the
      hypothalamus, pituitary and spinal cord remained unchanged. Only in the plasma a
      decrease in that peptide content was found. Furthermore, in vitro studies showed
      that the spontaneous and K(+)-stimulated release of beta-endorphin from the
      hypothalamus of rats which had been exposed to a conditioned stimulus was
      enhanced, whereas the release of alpha-neoendorphin from that tissue was
      attenuated. These results suggest a major role of the proopiomelanocortin system
      and, to the lesser extent, of the prodynorphin one in the mechanism of a
      conditioned fear-induced stress.

PMID- 1982695
TI  - Global in vivo replacement of choline by N-aminodeanol. Testing a hypothesis
      about progressive degenerative dementia: I. Dynamics of choline replacement.
AB  - Severe disruption of certain cholinergic pathways is a characteristic feature of
      Alzheimer's disease. Attempts to establish animal models by interfering with
      cholinergic function have not been very successful. We now present data which
      show a substantial and progressive replacement of free and phospholipid-bound
      choline by the novel choline isostere N-amino-N,N-dimethylaminoethanol during its
      dietary administration in place of choline. Free choline in blood fell to
      approximately 20% of controls after 10 to 30 days on diet. Phospholipid-bound
      choline in plasma was reduced to less than 15%, and in erythrocytes to about 22%.
      After 120 days of diet free and bound choline were reduced in most tissues to
      approximately 30% of controls. Only liver retained more than 80% of free choline.
      Acetylcholine was decreased to 33 to 50% of control. Total true and false
      transmitter in experimental animals was in all tissues less that acetylcholine in
      controls, suggesting that muscarinic transmission would be impaired. Moderate
      reduction of choline acetyltransferase activity was seen in striatum and
      myenteric plexus, and of QNB-binding in hippocampus, striatum and myenteric
      plexus.

PMID- 1982696
TI  - Global in vivo replacement of choline by N-aminodeanol. Testing a hypothesis
      about progressive degenerative dementia: II. Physiological and behavioral
      effects.
AB  - We have examined the progressive effects of replacement of dietary choline with
      NADe for a period of 120 days on a broad spectrum of behavioral and physiological
      functions known to involve the cholinergic system. The magnitudes of these
      effects tended to increase with time on the NADe diet, but those related to
      learning and memory were largely confined to the 60-120-day period. Neurochemical
      effects were concomitant with the replacement of Ch by NADe, being consistent
      with a hypocholinergic state as found in such progressive degenerative dementias
      as Alzheimer's disease. As cholinergic functioning was progressively impaired,
      basic physiological ("vegetative") processes appeared not to be affected.
      Apparently the rate at which the hypofunctional state developed was sufficiently
      slow for adjustments to occur, allowing the animal to adapt at a survival level
      to neurochemical changes. More complex behavioral functions were affected
      progressively, cognitive processes (e.g., learning and memory) being most
      sensitive and showing the least adaptability. We propose that the syndrome
      generated by NADe replacement of Ch represents an experimental model of
      progressive degenerative dementia.

PMID- 1982697
TI  - Alpha 2-adrenergic stimulation within the nucleus tractus solitarius attenuates
      vasopressin release induced by depletion of cardiovascular volume.
AB  - The functional role of the nucleus tractus solitarius (NTS) in the regulation of
      arginine-vasopressin (AVP) release mediated by baroreceptor activation was
      investigated by examining the effects induced by the presynaptic alpha-adrenergic
      agonist clonidine. The present data show that microinjection of clonidine into
      NTS resulted in a significant attenuation of AVP secretion induced by hypovolemia
      in the rat. This effect produced by NTS injection of 8 and 10 nmol clonidine was
      prevented by NTS pretreatment with the alpha 2-adrenoceptor blocker, yohimbine
      (10 nmol), indicating alpha 2-adrenergic receptors were required for the
      biological response. These findings suggest that catecholaminergic projections
      from NTS to hypothalamic vasopressinergic neurons play a facilitatory role in
      controlling AVP secretion.

PMID- 1982698
TI  - Kinetic comparison of rat pulmonary and renal gamma-glutamyl transpeptidase
      activities.
AB  - Glutathione (GSH) protects the lung against oxidative injury from environmental
      pollutants. gamma-Glutamyl transpeptidase (GGT) plays an integral role in the
      utilization and degradation of glutathione. Although GGT has been extensively
      studied in the kidney, little is known about GGT activity in the lung. This study
      compares pulmonary and renal GGT activities using L-gamma-glutamyl-p-nitroanilide
      as the substrate. The apparent Km values of pulmonary and renal GGTs were not
      significantly different. The pulmonary apparent maximum velocity was several
      orders of magnitude lower than that of the kidney. Inhibition studies, employing
      L-serine in the presence of 20 microM borate, revealed similar apparent Ki
      values. Pulmonary GGT behaves similar to renal GGT in respect to its affinity for
      substrates and inhibitors but has significantly less activity on a gram protein
      basis.

PMID- 1982699
TI  - [Changes in the general activation level in psychophysiologic studies--II. Values
      of auditory evoked potentials in relation to impression and perception and heart
      rate].
AB  - In psychophysiology all procedures used are accompanied with changes of general
      activation level (GAL) of the subjects. In our study these changes are
      characterized by self-assessment of the internal state and by the mean heart rate
      (HR) of each period. On the basis of these data group mean auditory evoked
      potentials (AEPs) were computed. The influence of the GAL on the N 110- and P 190
      amplitudes of the AEPs was analysed. There was no effect on the P 190-amplitude
      whereas the N 110-amplitude shows distinct responses on changes in GAL. These
      amplitudes diminished when the subjects reported a change of internal state. The
      diminishing of N 110-amplitudes took place as well at an increase as at a
      decrease of the internal state factors. Comparing the HR and the N 110 of the
      AEPs we found an inverse U-shaped dependence. These results are discussed in
      comparison to the literature. Furthermore a model which could elucidate the
      observed findings is presented for a critical discussion.

PMID- 1982701
TI  - [Symposium on Converting Enzyme Inhibitors in Cardiovascular Diseases. Sao Paulo,
      2 September 1989].

PMID- 1982700
TI  - [State and complexity-dependent symmetry identification of 2-dimensional patterns
      and evoked potentials].
AB  - To analyse the influence of structural complexity of visual patterns and of an
      operationally defined cognitive state on evoked potentials some on--line closed-
      loop experiments were carried out. Symmetrical checkerboard patterns generated by
      means of Walsh functions were used as stimuli. The inherent symmetry should be
      recognized by the subjects. The state was defined on the basis of the spectral
      power density distribution of the EEG measured in the time interval of one second
      before the stimulus onset. The two state values were labeled by the state of
      alpha wave dominance and the state of non alpha wave dominance. According to the
      definition for the state of alpha wave dominance 70% of the whole spectral power
      must be contained in the frequency range from 8 Hz until 13 Hz at least.
      Otherwise the prestimulus EEG are labeled by the concept of non alpha wave state.
      The influence of the cognitive state and of the structural complexity on the
      evoked potentials has been verified experimentally. Significantly higher
      amplitudes of the evoked potentials in the time range of 140 ms until 200 ms
      after stimulus onset are due to higher complexity of the stimuli. The state of
      alpha wave dominance led to significantly stronger negativity of the evoked
      potentials in the range of 280 ms until 400 ms after stimulus onset.

PMID- 1982702
TI  - A symposium: What is new in myocardial ischemia? A satellite meeting of the
      European Society of Cardiology Congress. Nice, France, September 1989.

PMID- 1982704
TI  - Proceedings of the Seventh International Congress of Biorheology, Nancy, France,
      18-23 June 1989. Part III.

PMID- 1982703
TI  - An avidin-biotin based enzyme-linked immunosorbent assay for dynorphin A 1-13.

PMID- 1982705
TI  - Can we reverse ischemic penumbra? Some mechanisms in the pathophysiology of
      energy-compromised brain tissue.
AB  - The region surrounding a focal cerebral infarct shows selective rather than
      generalized neuronal damage. The "ischemic penumbra" has been defined
      electrophysiologically as that region which shows a loss of electrical activity
      while retaining some metabolic viability (Astrup et al., Stroke, 1981:6:723-5).
      How factors that contribute to ischemic damage may cause such selective damage to
      subpopulations of neurones will be discussed. Particular attention will be
      directed to the cortical pyramidal cells, thought to be a major component of
      cerebral electrical activity. The N-methyl-D-aspartate (NMDA) class of glutamic
      acid receptors appears to have a role in certain aspects of ischemic damage,
      mediated through excitotoxins and calcium ions. The regulation of this receptor
      complex appears to be unaffected by ischemia, and thus it may provide a target
      for possible therapeutic interventions. Selective neuronal loss tends to be
      associated with neurotransmitter imbalance; therefore, treatments designed to
      correct this imbalance by affecting the activity of those cells less sensitive to
      ischemia may provide an alternative approach to establish normal cerebral
      function.

PMID- 1982706
TI  - The role of detoxifying systems in resistance of tumor cells to cisplatin and
      adriamycin.

PMID- 1982707
TI  - The use of sulphasalazine as a disease modifying antirheumatic drug.
AB  - SASP is a useful DMARD in RA and is probably useful in early ankylosing
      spondylitis, psoriatic arthropathy and reactive arthritis. It shares many of the
      characteristics of other DMARDs such as gold and penicillamine. It produces
      improvement in clinical and laboratory parameters of disease activity, with a
      slow onset of action--8-12 weeks elapse before beneficial effect is noted. SASP
      probably slows radiological progression of RA but definitive proof is difficult
      to obtain. Although side-effects are common, these are often managed by a
      reduction in dose, and serious adverse events requiring cessation of therapy are
      uncommon. Serious side-effects do occur however, and regular monitoring with full
      blood counts is recommended. The mechanism of action of SASP is unknown and this
      remains one of the principal areas of research interest.

PMID- 1982708
TI  - Combination therapy in rheumatoid arthritis.

PMID- 1982709
TI  - [Late gestoses. Selection of reports presented at the national scientific
      conference of the Czech Gynecologic and Obstetrical Society held in Prague March
      1-2 1990].

PMID- 1982711
TI  - Dialysis therapy in the 1990s. International symposium on Dialysis Therapy in the
      1990s. Osaka, October 5-6, 1989.

PMID- 1982712
TI  - Erythropoietin in the 90s. International Symposium, Wurzburg, March 23-24, 1990.

PMID- 1982710
TI  - The action of myocrisin on membrane bound sulphhydryl groups.

PMID- 1982713
TI  - Methods in Phase I. Proceedings of a seminar. Lyon 11-12 January 1990.

PMID- 1982714
TI  - Restrictive and electric disturbance in heart muscle diseases. Selected
      proceedings from the 2nd International Symposium on Cardiomyopathy and
      Myocarditis, September 14-16, 1988, Tokyo, Japan.

PMID- 1982715
TI  - Proceedings of the Second International Workshop and Symposium on Monoclonal
      Antibodies Against Human Red Blood Cells and Related Antigens. 1-4 April, 1990,
      Lund, Sweden.

PMID- 1982716
TI  - Abstracts of the International Workshop on Patient Decision Making in
      Cardiomyopathies: the Role of Echo/Doppler. Bari, Italy, 20-22 May 1991.
      Abstracts.

PMID- 1982717
TI  - [The central nervous system and immunity].
AB  - The neuroendocrine control of the immune response is mediated by products shared
      by both the nervous and the immune system. The "classical" neurotransmitters
      (monoamines, acetylcholine, oligo- and polipeptides) modulate the activity of the
      immunocompetent cells, and vice versa, the products of activated immunocompetent
      cells (interleukins) affect the neurons and the glia-cells. The autonomous
      innervation of the lymphatic tissue receives and transmits impulses. Activation
      of the immune system is accompanied by increased electrophysiological activity of
      the hypothalamus and by altered levels of various hormones. These changes
      contribute to the "fine tuning" of specificity of the immune response. The
      neuroendocrine regulatory mechanisms modulate the immune reactivity to a higher
      or a lower level, and determine the psychophysiological resistance or
      susceptibility to the infectious, autoimmune and neoplastic diseases.

PMID- 1982719
TI  - 1st International Conference on Antifungal Chemotherapy, ICAFC 90. September 24
      26, 1990, Oiso, Japan.

PMID- 1982718
TI  - Oral candidosis in HIV-infected patients. Prognostic value and correlation with
      immunological parameters.
AB  - In a prospective study, 29 patients were observed over a period of 42 weeks for
      signs of oral candidosis (OC), immunological parameters and other typical AIDS
      related events. Before the study started, no OC was observed in any of the
      patients. During the observation period, OC was diagnosed in 12 of the 29
      patients (41%). 5 of these 12 patients (42%) developed full-blown AIDS during the
      42 weeks. In contrast, a progression to AIDS was observed in only 1 of the 17
      patients (5.9%) without OC. The laboratory findings for patients with and without
      OC showed statistically significant differences for neopterin (23.6 against 14.4
      nmol l-1), CD4 counts (417 against 763/mm3) and CD4/CD8 ratios (0.45 against
      0.85). Based on these results, it seems justifiable to consider prophylactic
      measures such as pentamidine inhalation and/or treatment with zidovudine in HIV
      infected patients with immunodeficiency and occurrence of OC.

PMID- 1982720
TI  - [Tardive dyskinesia. A possible complication of chronic treatment with
      neuroleptics].
AB  - Tardive dyskinesia consists of abnormal involuntary movements at the oro-facial
      area (mouth, tongue, maxillary) or generalized choreoathetotic disorders of the
      limbs and trunk occurring in at least 10-20% of chronically neuropsychiatric
      patients exposed to neuroleptics. Age (over 50), gender (female), affective
      disorders, individual predisposition, type of drug, dosage and duration of
      neuroleptic exposure (over 3 months), anticholinergics, appear to be risk
      factors. In this brief review some current pathophysiological mechanisms and
      clinical therapeutical trials are also discussed.

PMID- 1982721
TI  - [A sudden exaltation].

PMID- 1982722
TI  - Observations with Norcuron in general surgery cases.
AB  - Norcuron, a neuromuscular blocking agent of medium duration of action has been
      applied to 50 general surgery patients. The muscle relaxant assured the muscle
      relaxation required for performing operations of 25'-180' duration, if required
      by repeating the drug administration. The drug had no cardiovascular side
      effects. It's action could be easily and rapidly antagonized. In spite of the
      relative overdosage used by the author unexpected phenomenon did not occur and
      the unwanted effects of Norcuron did not develop. The product is a myorelaxant
      which may be safely and flexibly used and the doses of which may be easily
      changed.

PMID- 1982723
TI  - Observations with tinset tablet in allergic respiratory tract diseases.
AB  - The effect of Tinset tablet (30 mg oxatomide) has been examined in 68 patients
      suffering from allergic diseases of the upper respiratory tract or from allergic
      diseases accidentally accompanying different pulmonary diseases. In general the
      daily doses were 2 x 1 tab., occasionally 2 x 2 tab., a number of 12-16-year old
      patients received only 1 tab. daily. On the basis of the clinical symptoms,
      spirometric examinations, and global evaluation it has been concluded that the
      drug may be used most successfully in seasonal rhinitis, allergodermatosis, and
      allergic conjunctivitis cases and in extrinsic allergic asthma of children. The
      therapeutic effectiveness of the drug is insignificant in perennial rhinitis and
      adult extrinsic asthma cases. The somnolence-inducing effect of the drug is
      notable (it developed in 50% of the patients). In 23 of the 68 patients weight
      gain, in 3 cases each gastric complaint or dryness of mouth developed.

PMID- 1982724
TI  - [Scandinavian nurses at the conference: economic know-how gives us influence in
      society].

PMID- 1982725
TI  - The function of chaperones during intracellular protein sorting, folding and
      assembly.

PMID- 1982726
TI  - [Dentofacial injuries (1)].
AB  - A significant percentage of people suffer dental traumatims along his life. In
      view of aesthetic and functional importance of dental traumatisms we carry out a
      aethiological and epidemiological revision, with a study of classification and
      localization of these lesions.

PMID- 1982727
TI  - Ist International Congress on Brain Electromagnetic Topography. September 12-14,
      1990, Osaka, Japan.

PMID- 1982728
TI  - Surface expression of CD11b/CD18 of pseudo-Pelger granulocytes in chronic myeloid
      leukaemia.
AB  - The aim of the present study was to evaluate the surface membrane glycoproteins
      of pseudo-Pelger granulocytes in six patients suffering from chronic myeloid
      leukaemia (CML). We studied the functional and immunochemical activities of five
      monoclonal antibodies (MoAb) minimally reactive with integrin familial antigens
      of pseudo-Pelger granulocytes. The study conducted with cytofluorimetric and
      immunological alkaline phosphatase anti-alkaline phosphatase (APAAP) analysis
      showed a decreased expression of CD11b/CD18 detected by antibodies OKM1, 60.1 and
      60.3 (P less than 0.001). Lymphocyte function associated antigen (LFA-1) was
      expressed in normal amounts in pseudo-Pelger granulocytes. There was decreased
      expression of CD11b/CD18 in pseudo-Pelger granulocytes with respect to controls
      (P less than 0.001) after stimulation with formyl-met-leu-phe (FMLP). We conclude
      that acquired pseudo-Pelger granulocyte dysfunction may be correlated to decrease
      of surface glycoprotein expression of CD11b/CD18.

PMID- 1982729
TI  - Family studies in von Willebrand's disease by analysis of restriction fragment
      length polymorphisms and an intragenic variable number tandem repeat (VNTR)
      sequence.
AB  - We have previously identified a microsatellite variable number tandem repeat
      region of the nucleotide sequence ATCT within intron 40 of the von Willebrand
      factor (vWF) gene. By polymerase chain reaction (PCR) amplification of this
      region, eight major alleles have been demonstrated in the South Wales population,
      with an overall heterozygosity rate of 75%. Direct sequencing has shown that the
      alleles correspond to lengths of between six and 14 ATCT repeats. In the present
      study we describe the use of this variable repeat sequence and previously
      reported restriction fragment length polymorphisms (RFLP) to study inheritance
      patterns in families with type I, IIA and severe type III von Willebrand's
      disease (vWD). The results confirm that analysis of this precisely localized
      intragenic locus provides a highly informative marker for gene tracking studies
      in the major forms of vWD.

PMID- 1982730
TI  - Brain glucose and energy metabolism during normal aging.
AB  - The mature, healthy, non-starved mammalian brain uses glucose only as a source of
      energy in the form of ATP, which is necessary for several metabolic processes,
      such as the maintenance of cellular homeostasis via ion homeostasis, maintenance
      of the integrity of cellular compartments, and intracellular transportation
      processes for the formation of several neurotransmitters, neurotransmission
      itself and a few anabolic reactions. Glucose breakdown contributes to the
      formation of the neurotransmitters: acetylcholine, glutamate, aspartate, gamma
      aminobutyrate, and glycine. Normal cerebral aging is associated with an incipient
      perturbation in both cerebral glucose and related metabolism, that determines an
      energy deficit and thus an imbalance in cell homeostasis after the 7th or 8th
      decade of human life, indicating a threshold phenomenon. This is evidenced by
      morphological/morphobiological abnormalities comprising neuronal loss and
      structural changes. These events are thought to cause a marked reduction in the
      biological plasticity of the brain, which may be severely involved after
      additional stress situations such as ischemia, hypoxia or hypoglycemia. The age
      related increasing perturbation of neuronal homeostasis may represent a stress
      situation capable of inducing heat shock proteins effecting gene activity. Thus,
      several age-related metabolic abnormalities at the cellular level, starting with
      a deficient neuronal glucose and energy metabolism, can be regarded as risk
      factors for neuronal damage and death, and hence reduced mental capacity.

PMID- 1982731
TI  - 40th Annual Pittsburgh Conference and Exposition, Atlanta, Georgia, 6-10 March
      1989.

PMID- 1982732
TI  - Analysis of anticancer drugs in biological fluids: determination of taxol with
      application to clinical pharmacokinetics.
AB  - Taxol, a novel antimitotic, antitumor agent is currently undergoing Phase 1
      clinical trials for the treatment of various tumors. An isocratic HPLC method has
      been developed for the determination of taxol in human plasma and urine. The
      method was then applied to the clinical pharmacokinetics of taxol following 6-h
      intravenous (i.v.) infusions at doses of 175 and 225 mg m-2. A mobile phase of
      methanol-acetate buffer (0.02 M, pH 4.5) (65:35, v/v) was used to elute a C8
      column with detection at 227 nm. The sample preparation involved extraction with
      t-butyl methyl ether followed by further clean-up of the sample by solid-phase
      extraction. The method was linear from 0.10-10 microM injected, with a
      chromatographic run time of 6 min. The results obtained from the clinical study
      indicate that the plasma pharmacokinetics of taxol are best characterized by a
      two compartment open body model. Additionally, the present study resulted in the
      detection of a previously unreported peak which may be a metabolite of taxol.

PMID- 1982733
TI  - National Symposium on Genetic Services for Underserved Populations. Arlington,
      Virginia, May 1989.

PMID- 1982734
TI  - Malaria vaccine development: pre-erythrocytic stages. Proceedings of a
      conference. National Naval Medical Center, Bethesda, Maryland, USA, 12-15 April
      1989.

PMID- 1982735
TI  - The fear behind the fear: a case study of apparent simple injection phobia.
AB  - The interrelations of multiple phobias are illustrated in the case of a female
      student whose presenting complaint of injection phobia did not at first appear to
      be related to her other fears. The rapid amelioration of her presenting complaint
      (sustained at three-month and eight-month follow-up) followed the discovery of
      functional relationships between these fears. The implications of the case with
      respect to Lang's (Anxiety and the Anxiety Disorders, 1985) work on the cognitive
      psychophysiology of emotion, and the investigations of McNeil and Berryman
      (Behavior Research Therapy 27, 233-236, 1989) and Rachman and Lopatka (Behavior
      Research Therapy 24, 653-660, 1986; Behavior Research Therapy 24, 661-664, 1986)
      are discussed.

PMID- 1982736
TI  - A case of maternity testing: exclusion by polymorphic VNTR markers of DNA.
AB  - The genetic markers of a Korean woman and her allegedly adopted child were
      compared to test her maternity. None of 21 conventional markers, including 8 red
      cell antigens, 6 red cell enzymes, and 7 serum proteins, excluded the maternity.
      These results indicate a maternal probability of 0.31 which was too low to
      conclude the true maternity. Human leukocyte antigen (HLA)-A, -B, -C and -DR
      haplotyping was also uninformative in this case. The maternity was consequently
      excluded by the observation of a difference in 2 of 5 variable number of tandem
      repeat (VNTR) markers.

PMID- 1982737
TI  - Mapping of the genes around MEN2A locus using pulsed-field gel electrophoresis.
AB  - The gene for multiple endocrine neoplasia type 2A (MEN 2A) is closely linked to
      RBP3 (retinol-binding protein 3, interstitial, probe IRBP.H4) and the DNA marker
      D10S15 (probe pMCK2), which have been assigned to the proximal long arm of
      chromosome 10 by linkage analysis both in Caucasian and Japanese populations. We
      have constructed a rare-cutting restriction map around the RBP3 and D10S15 loci
      by pulsed-field gel electrophoresis (PFGE). The RBP3 and D10S15 loci appeared to
      be within a single 160 kb MluI fragment. In 5 patients with MEN 2A, gene
      rearrangements, such as a gross deletion, were not found in the 880 kb NruI
      fragment which covered the closest region to the MEN-2A locus from the RBP3 and
      D10S15 loci.

PMID- 1982738
TI  - Biphasic effect of locally applied apomorphine and 2,3,4,5-tetrahydro-7,8
      dihydroxy-1-phenyl-1H-3-benzazepine on the release of striatal dopamine
      investigated by means of brain dialysis.
AB  - The effects of 3 kinds of dopamine (DA) agonists, apomorphine (APO), 2,3,4,5
      tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine (SKF-38393) and quinpirole
      (QPL), on DA release were examined in the caudate-putamen of the freely moving
      rat by means of microdialysis during local administration of various
      concentrations of these DA agonists. Infusion of 10(-4) M and 10(-5) M
      concentrations of APO and 10(-5) M and 10(-6) M of SKF-38393 induced a brief
      increase in DA release followed by a marked decrease. This phenomenon was
      sensitive to tetrodotoxin (10(-6) M) infusion. On the other hand, all the tested
      doses of QPL, 10(-4) M, 10(-5) M, 10(-6) M and 10(-7) M, reduced DA release
      without showing transient increase.

PMID- 1982740
TI  - Torch versus oven preceramic soldering of a nickel-chromium alloy.
AB  - Base metal preceramic solder joints have been described as unpredictable and
      inconsistent in tensile strength. Compared to base metal postoldered joints,
      presoldering with a gas-oxygen torch produces weaker joints that have increased
      porosity and voids. This investigation compared the tensile strength of base
      metal solder joints presoldered with a gas-oxygen torch to that of joints
      presoldered in a porcelain oven under vacuum. The mean (+/- SD) solder joint
      tensile strength was 460.0 (+/- 99.4) MPa for the oven-soldered and 520.2 (+/-
      37.8) MPa for the torch-soldered specimens. A strong, consistent, void-free
      preceramic solder joint was produced between a nickel-chromium base and gold
      solder by both torch- and oven-presoldering techniques; however, preceramic
      soldering with a torch tended to result in a stronger bond.

PMID- 1982739
TI  - The effects of halothane on the contents of putative transmitter amino acids in
      whole rat brain.
AB  - The effects of halothane on brain amino acid contents were investigated in rat by
      using a gas chromatography-mass spectrometry system. The contents of glycine and
      glutamate did not show any consistent changes in 1% or 2% halothane, but
      increased in 3% or 4% halothane. The levels of gamma-aminobutyric acid were not
      altered in any concentrations of halothane. The levels of aspartate increased in
      a dose-dependent manner up to 3% halothane, but returned to the control level in
      4% halothane. These findings suggest that halothane brings the alteration of
      brain amino acid contents by affecting their synthesis and catabolism.

PMID- 1982741
TI  - [Determination of pressure-volume relations from ventriculographs using catheter
      tip manometers].
AB  - The evaluation of cardiac function alone from pressure and volume data can lead
      to misinterpretations. By linking of pressure and volume data a variety of new
      parameters can be calculated. Computer techniques allow the evaluation not only
      of cardiac work, but also of acceleration work and the efficiency of heart power.
      As an example of double blind study with CHD patients the measurement of such
      parameters under invasive diagnostics is demonstrated, facilitating a detailed
      evaluation of cardiac function.

PMID- 1982743
TI  - Neurotransmitters in the cerebral cortex.

PMID- 1982742
TI  - [Acute changes of coronary and global hemodynamics in patients with angina
      pectoris and arterial hypertension caused by celiprolol and metoprolol].
AB  - In 30 hypertensives with angina pectoris the acute action of beta-blockers
      Celiprolol and Metoprolol on the global and coronary haemodynamics was tested
      within cardiac catheter diagnostics. In accordance with no long-term effects
      Metoprolol acts negatively inotrope, chronotrope as well as pre- and post-load
      increasing. Celiprolol lowered the pre- and postload, and increased the cardiac
      output, but did not influence the heart rate. Both medicaments increased coronary
      flow and myocardiac oxygen consumption. From the mentioned effects important
      conclusions for therapy with both Beta-blockers can be derived.

PMID- 1982744
TI  - [Medico-legal aspects of tooth injuries].
AB  - A model for the initial medical certificate is presented. It is a key document in
      the child's record and will constitute a reference during an expertise.

PMID- 1982745
TI  - [Apexification. Apexogenesis].
AB  - With the use of calcium hydroxide, apexification and apexogenesis will result in
      the formation of an apical barrier (osteo-cementum or similar hard tissue) or in
      the apical closure of the traumatised tooth, in order to realise later on, a
      hermetic and permanent root canal obturation.

PMID- 1982746
TI  - HLA-DP incompatibilities induce significant proliferation in primary mixed
      lymphocyte cultures in HLA-A, -B, -DR and -DQ compatible individuals:
      implications for allogeneic bone marrow transplantation.
AB  - The major part of the proliferative response in primary mixed lymphocyte cultures
      (MLC) is caused by HLA-DRB1 incompatibilities. In DRB1-matched pairs the
      proliferation induced by HLA-DRB3, -DQ and -DP mismatches may be unmasked. In
      most previous studies the influence of HLA-DP incompatibilities in primary MLC
      has been investigated in homozygous typing cells representing only a few Dw
      specificities. We were interested in determining the stimulatory capacity of
      isolated HLA-DP mismatches, ascertained by RFLP analysis, in primary MLC in HLA
      A, -B, -DR and -DQ compatible, unrelated heterozygous individuals of many
      different Dw specificities. Thirty-eight MLCs performed with cells from related
      pairs and 67 with cells from unrelated pairs were evaluated. All but nine of the
      MLCs were analyzed in both directions, giving a total of 201 investigated
      reactions. The relative responses (RR) in the three MLCs performed between DP
      incompatible, related pairs were all positive (RR greater than or equal to 8%).
      Eighty of 82 MLCs performed with cells from DP incompatible, unrelated
      individuals were positive, whereas 37 of 46 MLCs between DP compatible, unrelated
      pairs were negative (RR less than 8%) (p less than 10(-10)). The magnitude of the
      RR was influenced by the number of DP mismatches. Thus, the mean RR was
      approximately twice as high in MLCs in which responder and stimulator cells
      differed by two DP antigens (mean RR 60.5%) compared with reactions with only one
      DP mismatch (mean RR 35.4%) (p less than 10(-3)). RFLP-defined HLA-DP
      incompatibilities predict a positive primary MLC in HLA-A, -B, -DR and -DQ
      matched individuals with a high degree of accuracy (98%).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1982748
TI  - Failure of apraclonidine to prevent delayed IOP elevation after Nd:YAG laser
      posterior capsulotomy.
AB  - An elderly pseudophakic man with advanced open-angle glaucoma underwent Nd:YAG
      laser posterior capsulotomy. Pigment deposits were also removed from the anterior
      lens surface with laser applications. In spite of pre- and post-laser treatment
      with topical apraclonidine (Iopidine) and normal IOP 1 hour postoperatively, the
      patient presented the next day with visual acuity of 20/300, corneal edema, pain,
      and IOP of 60 mm Hg. Prompt treatment reduced the pressure and normal visual
      acuity was achieved. While apraclonidine prevents early post-laser elevation of
      IOP in most cases, some pressure elevations may be delayed or persist longer than
      the duration of action of the drug. Examination of patients with advanced
      glaucomatous optic nerve damage is recommended the day after anterior segment
      laser surgery, even when apraclonidine is used at the time of laser surgery and
      IOP is normal 1 to 2 hours postoperatively.

PMID- 1982747
TI  - Apraclonidine hydrochloride: an evaluation of plasma concentrations, and a
      comparison of its intraocular pressure lowering and cardiovascular effects to
      timolol maleate.
AB  - We performed a prospective, placebo-controlled, cross-over study in 20 young
      healthy female volunteers. We evaluated both the cardiovascular and IOP effects
      of both timolol maleate and apraclonidine hydrochloride. In addition, we
      evaluated the plasma levels of various apraclonidine concentrations. We utilized
      0.5% timolol and both the 0.25% and 0.50% concentrations of apraclonidine. Both
      timolol and apraclonidine lowered IOP comparably. Timolol lowered the resting
      pulse rate and blunted exercise-induced tachycardia. Apraclonidine did not affect
      blood pressure or heart rate any differently than placebo. We detected plasma
      levels of apraclonidine in many individuals for up to 8 hours. These serum levels
      were variable and did not appear to relate to the quantity of IOP lowering.

PMID- 1982749
TI  - Epinephrine effects on major cell types of the aqueous outflow pathway: in vitro
      studies/clinical implications.
AB  - We have investigated the possibility that direct cellular effects may mediate the
      action of EPI to lower the IOP. To do this, cultured HTM and SCE cells were grown
      as monolayers over a millipore-filter support structure. The monolayers were
      exposed to various adrenergic agonists and antagonists while flow of the
      perfusate (DME + 5% FBS) was measured using a specially-designed computer-linked
      apparatus. Exposure of the cells to 10(-5) M EPI for around 2 hours led to a
      rapid twofold increase in HC which gradually declines over the next 12 hours.
      Continuous exposure of either cell type (ie, HTM or SCE cells) to EPI or ISO
      resulted in a four- to eightfold increase with a maximal effect measured around
      10 hours and a half maximal effect at 2.5 hours. Administration of c-AMP alone
      gave similar responses. In agreement with clinical studies, timolol blocks EPI's
      effect completely while betaxolol acted as a partial antagonist. These findings
      suggest that the cellular changes and the increase in HC are mediated by a beta-2
      receptor. There are many similarities between the responses observed using our in
      vitro system and the IOP-lowering response observed in vivo after the topical
      application of EPI (eg, concentration, time course, duration, and magnitude). The
      clinical implications of these preliminary results are discussed and it is
      proposed that the described in vitro system may be useful to select new
      adrenergic drugs for glaucoma therapy.

PMID- 1982750
TI  - Central effect of the potent long-acting H1-antihistamine levocabastine.
AB  - The effects of levocabastine (R 50 547; CAS 79516-68-0) on the central nervous
      system were studied in comparison with those of diphenhydramine, ketotifen and
      azelastine. At high doses, levocabastine caused a decrease in locomotor activity,
      prolongation of thiopental-induced sleep, depression of acetic acid-induced
      writhing in mice and inhibition of active avoidance response in rats, but these
      adverse effects were much less potent than those seen in diphenhydramine,
      ketotifen and azelastine. Oxotremorine-induced tremor and salivation in mice were
      delayed after extremely high dosage of levocabastine; however, these were much
      less effective than those seen after diphenhydramine and ketotifen. Levocabastine
      did not affect the tonic extensor seizure induced by maximal electroshock in mice
      which is different from that of diphenhydramine. In EEG analysis, levocabastine
      at a dose of 20 mg/kg caused no significant changes in the EEG recorded from the
      frontal cortex, occipital cortex, hippocampus and amygdala in rats with chronic
      electrodes.

PMID- 1982752
TI  - Some characteristics of rat nigrostriatal dopaminergic neuroconnection during
      development--a combined immunocytochemical and electron-microscopic study.
AB  - The characteristics of the nigrostriatal dopaminergic neuroconnections in
      developing rats are studied by combined immunocytochemical and electron
      microscopic techniques, with an antibody to tyrosine hydroxylase (TH). From the
      embryonic day 21 on, some of the TH-positive nerve fibers are densely packed in
      the striatum to form a patch-like dopamine island. The percentage of the TH
      positive nerve terminals among the labeled profiles is much higher inside than
      outside the dopamine island (P less than 0.01). On the other hand, the TH
      positive terminals mainly form symmetrical axon-dendritic synapses, while most of
      the TH-negative terminals form asymmetrical axon-spinous synapses. The functional
      significance of the characterized dopaminergic connection is discussed.

PMID- 1982751
TI  - Pharmacology of the new H1-receptor antagonist setastine hydrochloride.
AB  - Setastine HCl (N-(1-phenyl-1-[4-chlorophenyl])-etoxy-ethylene-perhydroazepine
      hydrochloride, Loderix; CAS 64294-95-7) is a potent antagonist of histamine H1
      receptor mediated responses. The antihistamine activity of the compound is
      similar to that of clemastine fumarate in the following assays: histamine-induced
      lethality and bronchospasm in guinea-pigs, plasma extravasation in rats, and
      contractile action in isolated guinea-pig ileum. Setastine HCl inhibits
      anaphylactic shock in guinea-pigs sensitized by horse serum. No antiserotonin,
      anticholinergic and antiadrenergic effect of the compound can be detected.
      Setastine HCl has a long lasting (up to 16 h) antihistamine effect with a good
      oral effectiveness. It shows no cardiovascular effects in cats. Setastine HCl
      shows a much weaker CNS depressant activity than clemestine fumarate measuring
      inhibition of amphetamine-induced hypermotility, rotarod performance,
      potentiation of ethanol-narcosis in mice, and prolongation of hexobarbital
      sleeping time in rats. In displacement studies (3H-mepyramine) setastine HCl had
      significantly weaker affinity for the central nervous system (CNS) H1-receptors
      than clemastine fumarate. It is concluded that setastine HCl is a non-sedative
      highly active H1-antagonist.

PMID- 1982754
TI  - Multiple endocrine neoplasia.

PMID- 1982753
TI  - Recombinant bivalent live vaccines against neonatal colibacillosis in piglets.
AB  - The genes of colonization factor K88 and avirulent heat-labile enterotoxin LT A
      B+ of enterotoxigenic E. coli (ETEC) have been ligated, and a vaccine strain
      containing recombinant plasmid that efficiently expresses two antigens has been
      obtained. Using the activity of beta-galactosidase as a selection marker instead
      of drug resistance, another bivalent vaccine strain with the same expression
      level has also been constructed. The vaccine strains have no toxicity and do not
      cause any adverse reactions. In challenge study and field trials, a high degree
      of protection from colibacillosis was afforded to piglets when their dams were
      immunized orally or parenterally. Practice of bivalent live vaccines including
      colonization factor and enterotoxin antigens and without antibiotic resistance
      gene shows effective.

PMID- 1982755
TI  - Autologous transplantation in acute leukemias, including purging.

PMID- 1982756
TI  - Mode of action of beta-adrenergic blocking drugs in hypertension.
AB  - Although they have been in use for over 20 years, the antihypertensive mode of
      action of beta-blocking drugs remains a matter for debate. Blood pressure falls
      with beta-blockers that have beta 1-selectivity, intrinsic sympathomimetic
      activity and membrane activity, but not those with a high level of pure beta
      stimulation. Several suggestions have been made to explain this effect; a direct
      action on the central nervous system, adrenergic neurone blocking, perhaps via
      pre-synaptic beta 2-receptors, anti-renin activity, an increase of vasodilator
      prostaglandins, effects secondary to reduced cardiac output, and resetting of
      baroreceptors secondary to reduced pressor peaks to various pressor stimuli from
      the reduction in cardiac activity consequent to beta-blockade. There are also
      beta-blocking drugs which additionally have direct action to reduce peripheral
      resistance, via beta 2-mediated vasodilation, an alpha-blocking action or a
      direct vasodilator activity. Most attention has been given to a possible
      correlation to the effect of beta-adrenoceptor blocking drugs on the blood
      pressure and renin levels. Several investigations have found patients with high
      renin levels respond best, normal renin patients respond less well and low renin
      patients relatively poorly. However, others have not found a clear relationship.

PMID- 1982757
TI  - Subtype-selective modulation of human beta 1- and beta 2-adrenoceptor function by
      beta-adrenoceptor agonists and antagonists.
AB  - In healthy volunteers a 14-day treatment with the selective beta 1-adrenoceptor
      agonist xamoterol (2 x 200 mg/day) desensitized beta 1-adrenoceptor-mediated
      physiological effects, but did not affect beta 2-adrenoceptor-mediated effects;
      in contrast, a 9-day treatment with the selective beta 2-adrenoceptor agonist
      procaterol (2 x 50 micrograms/day) desensitized beta 1-adrenoceptor-mediated
      physiological effects, but did not affect beta 1-adrenoceptor-mediated effects
      suggesting that in general in man long-term treatment with beta-adrenoceptor
      agonists down-regulates beta-adrenoceptors, but in a beta-adrenoceptor subtype
      selective manner. Similarly, in patients undergoing coronary artery bypass
      grafting chronic treatment with different beta-adrenoceptor antagonists without
      intrinsic sympathomimetic activity subtype-selectively up-regulated beta
      adrenoceptors: non-selective antagonists (propranolol, sotalol) increased both
      cardiac beta 1- and cardiac, saphenous vein and lymphocyte beta 2-adrenoceptors,
      whereas beta 1-selective antagonists (metoprolol, atenolol, bisoprolol) increased
      only cardiac beta 1-, but not cardiac, saphenous vein or lymphocyte beta 2
      adrenoceptors. Such a subtype-selective modulation of human beta 1- and beta 2
      adrenoceptors should be taken into consideration when treating patients
      chronically with beta-adrenoceptor agonists and/or antagonists.

PMID- 1982758
TI  - Comparative properties of various beta-blockers, with an outlook to the future.
AB  - Several beta-adrenoceptor blockers with various ancillary properties besides beta
      receptor blockade are now available for clinical use. In the treatment of
      hypertension, angina pectoris, and certain types of cardiac arrhythmia the
      therapeutic benefit is mediated by beta 1-receptor blockade, whereas the blockade
      of beta 2-adrenoceptors does usually not contribute to the therapeutic efficacy
      and is rather associated with adverse reactions. Accordingly, all properties
      other than beta 1-adrenoceptor blockade should be considered as ancillary
      properties. The following properties of beta-blockers and the therapeutic
      relevance of these properties are to be discussed, together with pertinent
      examples of the drugs involved: beta 1-receptor selectivity and the degree of
      beta 2-receptor blockade; intrinsic sympathomimetic activity (ISA); duration of
      action (to be discussed in connection with the pharmacokinetic properties in
      Prof. Borchard's presentation); lipophilicity, brain penetration and CNS side
      effects, and cardioprotective properties (secondary prevention following
      myocardial infarction). Most of these properties have been investigated in full
      detail and a wide variety of compounds possessing one or more of these properties
      have been introduced. With respect to the future, beta 1-adrenoceptor selectivity
      remains an interesting issue, although it is difficult to imagine that compounds
      which are even more beta 1-selective than bisoprolol can be developed. The
      cardioprotective activity of beta-blockers deserves further investigations, in
      particular with respect to the underlying mechanisms. Finally, many new beta
      blockers are now becoming available with an additional vasodilator component
      which may be caused by different mechanisms, like 'direct' vasodilation, beta 2
      receptor agonism, alpha-adrenoceptor blockade, or angiotensin-converting enzyme
      inhibition. The various mechanisms and possible clinical relevance will be
      discussed.

PMID- 1982759
TI  - Pharmacokinetics of beta-adrenoceptor blocking agents: clinical significance of
      hepatic and/or renal clearance.
AB  - A great number of beta-adrenoceptor blocking drugs are now available for clinical
      use which show great differences with respect to their pharmacokinetic
      properties. Bioavailability might be low because of a low absorption rate after
      oral application in the case of hydrophilic drugs like atenolol or might be low
      because of a high first-pass effect in the liver in the case of metoprolol or
      propranolol. Plasma levels of these latter drugs may vary considerably and
      inhibition of their oxidative metabolism by cimetidine may lead to an increase of
      peak plasma concentrations. In general, lipophilic beta-blockers are metabolized
      in the liver whereas hydrophilic agents are eliminated in the kidneys as
      unchanged drugs. Dose has to be adjusted according to renal function in the case
      of atenolol, carteolol, nadolol, sotalol and acebutolol, which is transformed
      into the active metabolite diacetolol. Drugs like bisoprolol, betaxolol and
      pindolol are eliminated via the liver and the kidneys. Bisoprolol, for example,
      shows a balanced clearance as it is eliminated to about 50% in the liver and 50%
      via the kidneys. Failure of one clearance organ (liver, kidney) leads to a
      maximally twofold increase in plasma half-life of bisoprolol. Being aware of the
      observation that some drugs show a long terminal half-life, it has been
      demonstrated that plasma levels correlate to duration of action. This is of major
      importance for the treatment of coronary heart disease as a once-daily dose
      should be active for 24 h.

PMID- 1982760
TI  - Corneal and conjunctival/scleral penetration of p-aminoclonidine, AGN 190342, and
      clonidine in rabbit eyes.
AB  - The ocular penetration pathways of three alpha 2-adrenergic agents (p
      aminoclonidine, AGN 190342, and clonidine) were investigated in rabbits both in
      vitro and in vivo. The corneal permeabilities of the compounds correlated
      positively with their octanol/water distribution coefficients. The ocular drug
      absorption via corneal and conjunctival/scleral penetration routes was evaluated
      separately after drug perfusion in vivo. In most cases, the corneal route was the
      major pathway for the intraocular drug absorption. However, the
      conjunctival/scleral penetration pathway was the predominant pathway for the
      delivery of p-aminoclonidine, the least lipophilic compound among the three
      drugs, to the ciliary body. The drug concentration in the iris was contributed
      mainly by the corneal route and correlated well with drug lipophilicity.

PMID- 1982761
TI  - Dose-response comparison of broxaterol and salbutamol pressurized aerosols.
AB  - The bronchodilating activity and tolerability of broxaterol and salbutamol
      administered by pressurized metered dose inhalers have been compared in 9 adult
      patients with bronchial asthma and clinically stable and reversible bronchospasm.
      Placebo was used as a control. On 3 different days broxaterol and salbutamol in
      cumulative doses of 100, 200 and 400 micrograms and placebo were administered
      every 30 min according to a double-blind, Latin-square design. After each dose of
      broxaterol and salbutamol the increases in FVC and FEV1 were always significantly
      larger than after placebo. Broxaterol at the doses tested induced a
      bronchodilator response which depended on the dose according to a relation not
      significantly different from a straight line, and with a potency at least
      comparable to that of salbutamol. The tolerability of the two drugs was good:
      only in 1 patient were slight tremors observed after the highest dose of each
      drug. The bronchodilating activity and the tolerability of broxaterol were not
      significantly different from those of salbutamol at the same doses.

PMID- 1982762
TI  - Pharmacokinetics after a single oral dose of bopindolol in patients with
      cirrhosis.
AB  - The plasma concentration-time curve of the hydrolysis product of bopindolol has
      been investigated in 14 patients with cirrhosis and in 15 healthy volunteers
      given a single oral dose of 2 mg bopindolol. Cirrhosis was confirmed by history
      and clinical examination or liver biopsy. The time to maximum concentration,
      maximum concentration and AUC of hydrolyzed bopindolol were similar in the
      patients and controls. However, the elimination half-life was 6.0 h in controls
      and 9.5 h in cirrhotics. Antipyrine clearance was markedly decreased in patients
      with cirrhosis, but no correlation was found with the pharmacokinetic parameters
      of hydrolysed bopindolol. Although the AUC was not significantly altered in
      patients with cirrhosis, the longer half-life of hydrolysed bopindolol suggests
      impairment of its disposition in liver disease, which could lead to significant
      accumulation of drug during chronic dosing.

PMID- 1982763
TI  - Comparative enantioselective pharmacokinetic studies of celiprolol in healthy
      volunteers and patients with impaired renal function.
AB  - The pharmacokinetics of the beta 1-selective adrenergic antagonist (R,S)
      celiprolol has been studied after oral administration of 200 mg celiprolol-HCl to
      8 healthy volunteers and 8 patients with various degrees of impaired renal
      function. No significant difference was found between the two enantiomers in the
      control group or in the patients. In healthy volunteers an average of 9.8% of the
      dose of R-(+)-celiprolol and 9.5% of S-(-)-celiprolol was recovered unchanged in
      the urine. Renal impairment reduced the urinary excretion of both enantiomers to
      the same extent according to the severity of the uraemia, producing higher AUCs.
      Nevertheless, the terminal half-lives of the R- and S-enantiomers were not
      significantly different between the groups. Dosage reduction in patients with
      renal impairment does not seem to be necessary.

PMID- 1982765
TI  - New aspects of pathophysiology and treatment of polycystic ovary syndrome. First
      Tokyo Conference on Reproductive Physiology. Tokyo, August 26, 1989.

PMID- 1982764
TI  - A lack of pharmacokinetic interaction between ranitidine and piroxicam.
AB  - The effects of piroxicam (40 mg) on the pharmacokinetics of ranitidine (150 mg)
      and of ranitidine (150 mg bid) on the pharmacokinetics of piroxicam (20 mg) were
      assessed in two 2-way crossover studies in two groups of 18 healthy male
      subjects. In the first study there were no statistically significant differences
      between the pharmacokinetic variables for ranitidine in the presence or absence
      of piroxicam. The mean maximum plasma concentration (Cmax) was 467 ng.ml-1 for
      ranitidine alone and 466 ng.ml-1 in the presence of piroxicam: mean area under
      the plasma concentration vs time curve (AUC) was 2460 h.ng ml-1 and 2551 h.ng ml
      1 respectively; and the mean terminal half-life (t 1/2) was 3.6 h and 3.8 h
      respectively. In the second study there were no statistically significant
      differences between the pharmacokinetic variables for piroxicam in the presence
      or absence of ranitidine. The mean Cmax was 2.1 micrograms.ml-1 in the presence
      of placebo and 2.0 micrograms.ml-1 in the presence of ranitidine respectively;
      mean AUC was 133 h.microgram ml-1 and 137 h.microgram ml-1 respectively, and the
      mean t 1/2 was 53.6 h and 54.5 h respectively.

PMID- 1982766
TI  - Proceedings of the 4th workshop on tooth morphogenesis and development
      (continuation). Arc and Senans, France, May 30-June 2, 1990.

PMID- 1982767
TI  - The effect of acivicin, an inhibitor of gamma-glutamyl transpeptidase on mouse
      molar development in vitro.
AB  - Gamma-glutamyl transpeptidase (GGT) is a membrane-bound enzyme found on the
      surface of cells having secretory or resorptive functions. GGT has been found to
      be strongly localized in the stellate reticulum of the developing tooth. It has
      been proposed that the role for GGT in tooth development is related to the
      transport of amino acids into the cell via the gamma-glutamyl cycle. In order to
      ascribe a role for GGT and the stellate reticulum in the developing tooth, the
      activity of GGT was inhibited by a daily 1 hour application of the glutamine
      analog, acivicin (Upjohn), to mouse first molar tooth germs in serum free organ
      culture for periods of 5 to 8 days. Acivicin treatment effectively arrested tooth
      development. Additionally, tooth germs were allowed to recover for 4 to 7 days
      following a 4 day treatment with acivicin or they were incubated in media
      supplemented with additional glutamine or nucleosides during the acivicin
      treatment. Tooth germs were able to recover when returned to control medium.
      However, treated teeth were smaller in size than the controls. Glutamine
      partially compensated for the acivicin treatment. Nucleotide supplemented media
      appeared to almost completely override the inhibitory effect of acivicin. It
      appears that the inhibition by acivicin is primarily due to its effect on DNA and
      RNA synthesis. The inhibition of the gamma-glutamyl cycle by acivicin was
      unaffected by the addition of glutamine or nucleosides. Therefore, inhibition of
      the gamma-glutamyl cycle and GGT does not seem to significantly affect the
      development of teeth at the stages studied.

PMID- 1982769
TI  - Current problems in clinical hypertension: summary of a workshop held in
      Martinique, 29-31 October 1989.
AB  - Three major clinical problems in hypertension were discussed by an international
      group of investigators during a 3-day workshop. In particular, the type of
      treatment, what level of blood pressure to treat and what special considerations
      are required in certain categories of patients were the focus of interest. The
      findings of the meeting are outlined here.

PMID- 1982768
TI  - Tubulosine: an antitumor constituent of Pogonopus speciosus.
AB  - From the antitumor-bioactive sap of Pogonopus speciosus, tubulosine [1] was
      isolated, by activity-directed fractionation using the brine shrimp lethality
      test, as the major antitumor constituent. 1H-nmr assignments, obtained from
      HETCOR and COSY, and X-ray crystallographic results are reported for the first
      time. Psychotrine [2] was also isolated, and its spectral data are also reported.

PMID- 1982770
TI  - Implications of the primary prevention trials against coronary heart disease.
AB  - The bulk of the mortality (60%) in hypertension occurs in those with mild to
      moderate elevations of blood pressure, and the chief hazard is coronary disease.
      Although progression in the severity of hypertension has been slowed with drug
      therapy, the benefits for coronary outcome and all-cause mortality have been
      equivocal. Only a 10% reduction in coronary heart disease morbidity and mortality
      has been shown, an improvement that is not only small, but is statistically
      insignificant. Only vascular events such as renal failure, stroke, aortic
      dissection and cardiac failure have been reduced by antihypertensive therapy.
      Recent trials comparing beta-blockers with other antihypertensive drugs have
      failed to show the expected promise based on their effectiveness following a
      myocardial infarction. However, two large trials suggest that they may be
      effective against coronary heart disease in male non-smokers. A number of
      possible reasons for this therapeutic failure to reduce coronary heart disease
      have been postulated. The trials may have been too short to significantly affect
      the atherosclerotic progression. Also, sample sizes were too small to detect a
      sizeable reduction in coronary heart disease events. Furthermore, no attention
      was paid to improvements in the coronary heart disease risk profile, since drugs
      currently in use are known to have adverse effects on blood lipids, glucose
      tolerance and uric acid. It is even possible that a predisposition to sudden
      death is associated with antihypertensive therapy. The trials suggest that in
      attempts to prevent coronary heart disease, control of smoking and of serum
      lipids are particularly important in hypertensive persons and may be more
      effective than controlling the blood pressure alone.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1982771
TI  - Local mechanisms of blood flow control by perivascular nerves and endothelium.
AB  - In addition to the classical transmitters noradrenaline and acetylcholine, other
      transmitters have been identified in perivascular nerves, including 5
      hydroxytryptamine, ATP and a number of peptides. This paper discusses pre- and
      postjunctional neuromodulation of vascular transmission, and cotransmission
      involving noradrenaline, ATP and neuropeptide Y in sympathetic nerves,
      acetylcholine and vasoactive intestinal polypeptide in parasympathetic nerves,
      and substance P, calcitonin gene-related peptide and ATP in 'sensory-motor'
      nerves. Vasomotor nerves derived from intrinsic neurones, for example in the
      heart and gut, are also discussed. Subpopulations of endothelial cells store and
      release a variety of substances, including acetylcholine, substance P, ATP, 5
      hydroxytryptamine, vasopressin and angiotensin II, that act on receptors on
      endothelial cells and lead to the production of endothelium-derived relaxing
      factor (identified as nitric oxide) which, in turn, produces vasodilation in
      response to changes in flow and hypoxia. Endothelium-derived contracting factors
      such as endothelin may also be released. There appears to be a resting dynamic
      balance between endothelium-derived vasodilator tone and sympathetic
      vasoconstrictor tone, which is altered under different physiological and
      pathophysiological circumstances. Long-term (trophic) interactions between
      perivascular nerves and endothelial cells are discussed, as are the changes in
      vascular control mechanisms that occur with ageing and hypertension and in the
      nerves that remain following trauma or surgery.

PMID- 1982772
TI  - [Molecular basis of phenylketonuria].

PMID- 1982773
TI  - Pharmacokinetics of a single intravenous and oral dose of pafenolol--a beta 1
      adrenoceptor antagonist with atypical absorption and disposition properties--in
      man.
AB  - The pharmacokinetics of pafenolol were studied in eight young healthy
      individuals. The doses were 10 mg iv and 40 mg orally. Each dose was labeled with
      100 microCi [3H]pafenolol. The plasma concentration-time curve of the oral dose
      exhibited dual maxima. The second peak was about four times higher than the first
      one. Maximum concentrations were attained after 0.9 +/- 0.2 and 3.7 +/- 0.6 hr.
      The mean bioavailability (F) of the oral dose was 27.5 +/- 15.5%. The reduction
      in F was due mainly to incomplete gastrointestinal absorption. The drug was
      rapidly distributed to extravascular sites; t1/2 lambda 1 was 6.6 +/- 1.8 min.
      The volumes of distribution were Vc = 0.22 +/- 0.08 liter/kg, Vss = 0.94 +/- 0.17
      liter/kg, and Vz = 1.1 +/- 0.16 liters/kg. The iv dose of pafenolol was excreted
      in unchanged form in the urine to 55.6 +/- 5.1% of the given dose and in the
      feces to 23.8 +/- 5.7% within 72 hr. The corresponding recoveries of the oral
      dose were 15.8 +/- 5.9 and 67.0 +/- 10.2%, respectively. About 10% of both doses
      was recovered as metabolites in the excreta. Approximately 6% of the oral dose
      was metabolized to nonabsorbable compounds in the intestine. The mean total
      plasma clearance was 294 +/- 57 ml/min, of which renal clearance, metabolic
      clearance, and gastrointestinal and/or biliary clearance were responsible for 165
      +/- 31, 31 +/- 15, and 95 +/- 32 ml/min, respectively. The half-life of the
      terminal phase determined from plasma levels up to 24 hr after dosing was 3.1 +/-
      0.3 hr for the iv dose and 6.7 +/- 0.7 hr for the oral dose.

PMID- 1982774
TI  - Effects of single doses of propiomazine, a phenothiazine hypnotic, on sleep and
      oxygenation in patients with stable chronic obstructive pulmonary disease.
AB  - Serious respiratory depression may occur in patients with chronic obstructive
      pulmonary disease (COPD), receiving hypnotics during acute exacerbations.
      However, in a previous study on oxygenation during sleep in patients with stable
      hypoxemic non-hypercapnic COPD, we were unable to demonstrate a significant
      negative effect from single doses of nitrazepam and flunitrazepam. We have now
      investigated the effects of propiomazine, a phenothiazine hypnotic, in a double
      blind randomized cross-over study of oxygen saturation and apneas during sleep
      and other sleep variables in 12 non-obese hypoxemic but clinically stable
      theophylline-treated COPD patients (PaO2 8.1 kPa, PaCO2 5.6 kPa, FEV1 31% of
      predicted value). None of the respiratory variables were adversely affected by a
      single oral dose of 25 mg propiomazine, whereas total sleeping time and the sleep
      efficiency index increased.

PMID- 1982775
TI  - [Pharmacology of molluscan giant neurons].

PMID- 1982776
TI  - [Pain therapy for urologic cancer patients at the Potsdam district hospital-
      initial results].
AB  - After two years the results of cancer pain treatment in urological patients at
      the district hospital Potsdam are presented. In 15 patients the WHO recommended
      three-stage analgesics plan was used successfully.

PMID- 1982777
TI  - Phenothiazine compounds enhance phentolamine effects on platelet aggregation and
      thromboxane B2 production.
AB  - In the present study we investigated the influence of phentolamine and the
      phenothiazine compounds chlorpromazine and trifluoperazine on human platelet
      aggregation as well as the effect of the association of phentolamine and the
      phenothiazines on responses to adenosine diphosphate, collagen, thrombin,
      ionophore A23187 and phorbol-myristate acetate, release reaction, thromboxane B2
      synthesis and intraplatelet cyclic adenosine monophosphate levels. Phentolamine
      and phenothiazines exerted a dose-dependent inhibitory effect on aggregation
      induced by different concentrations of adenosine diphosphate and decreased the
      response to other agonists; furthermore, the phenothiazines enhanced the
      inhibitory effects of phentolamine on aggregation and thromboxane B2 synthesis,
      without influencing intraplatelet cyclic adenosine monophosphate levels. Phorbol
      ester-induced platelet activation was also inhibited in a dose-dependent way by
      each compound and by an association of phentolamine and phenothiazines,
      suggesting that the antiplatelet properties of these compounds might also be
      ascribed to intracellular events.

PMID- 1982778
TI  - Increased activity of tyrosine hydroxylase in the cerebellum of the X-irradiated
      dystonic rat.
AB  - The exposure of the cephalic end of rats to repeated doses of X-irradiation (150
      rad) immediately after birth induces a long-term increase in the noradrenaline
      (NA) content of cerebellum (CE) (+ 37.8%), and a decrease in cerebellar weight
      (65.2% of controls), which results in an increased NA concentration (+ 109%).
      This increase in the neurotransmitter level is accompanied by a dystonic syndrome
      and histological abnormalities: Purkinje cells (the target cells for NA afferents
      to CE) fail to arrange in a characteristic monolayer, and their primary dendritic
      tree appears randomly oriented. The injection of reserpine 0.9 and 1.2 mg/kg ip
      to adult rats for 18 h depletes cerebellar NA content in both controls (15.7 +/-
      4 ng/CE and 2.8 +/- 1.5 ng/CE, respectively) and X-irradiated rats (17.1 +/- 1
      ng/CE and 8.3 +/- 2 ng/CE, respectively). The activity of tyrosine hydroxylase
      (TH) in CE of adult rats, measured by an in vitro assay, is significantly
      increased in neonatally X-irradiated animals when compared to age-matched
      controls (16.4 +/- 1.4 vs 6.32 +/- 0.6 nmol CO2/h/mg prot., p less than 0.01). As
      observed for NA levels, a net increase in TH activity induced by the ionizing
      radiation is also measured: 308.9 +/- 23.8 vs 408.2 +/- 21.5 nmol CO2/h/CE, p
      less than 0.01 (controls and X-treated, respectively). These results suggest that
      X-irradiation at birth may induce an abnormal sprouting of noradrenergic
      afferents to CE. The possibility that these changes represent a response of the
      NA system to the dystonic syndrome is discussed.

PMID- 1982779
TI  - The effect of acute and repeated hyperammonemia on gamma-glutamyl transpeptidase
      in homogenates and capillaries of various rat brain regions.
AB  - The effect of hyperammonemia of varying degree and duration on the gamma-glutamyl
      transpeptidase (GGT) activity was studied in the homogenates and capillaries of
      different brain regions of the rat. "Acute" hyperammonemia (750 and 600 mg of
      ammonium acetate per kg b.w. were injected i.p. at 30 min interval, and the
      animals were decapitated immediately), in which blood ammonia was increased 14
      fold, and brain ammonia six-fold above the control level, produced a 20% increase
      of the enzyme activity in cerebellum, and a 17% decrease in gyrus dentatus, but
      had no effect in the frontal cortex and the CA1 and CA3 regions of hippocampus.
      "Subchronic" hyperammonemia (two injections of 600 mg ammonium acetate/kg were
      given at 24 h intervals, and tissue samples were removed 24 h later), that was
      accompanied by only a 60% increase of blood or brain ammonia, increased the
      activity in cerebellum to 38% above control, but produced no effect in the other
      brain regions. "Chronic" hyperammonemia (three injections of 600 mg ammonium
      acetate/kg at 24 h intervals and excision of tissue samples 30 min after the last
      injection), in which blood and brain ammonia were, respectively, 60 and 100%
      higher than in control animals, elevated the GGT activity in the cerebellum by
      57%, in CA1 by 15%, and in CA3 by 21%, but produced no effect in the frontal
      cortex or gyrus dentatus. By contrast, "chronic" hyperammonemia produced a 30%
      increase of GGT activity in cerebral cortical capillaries, but only a 10%
      increase in hippocampal capillaries, and no change in cerebellar capillaries. The
      results suggest that, hyperammonemia of relatively long duration may contribute
      to the enhancement of brain GGT activity observed in chronic forms of hepatic
      encephalopathy. However, ammonia does not appear to activate the enzyme directly.

PMID- 1982780
TI  - The relationship of the metachromatic leukodystrophies to neuropsychiatric
      disorders.
AB  - The possible relationship between the metachromatic leukodystrophies and
      neuropsychiatric disorders is reviewed. Four kinds of evidence are considered:
      psychiatric symptoms as preemergent markers of the neurodegenerative process;
      increased behavioral problems in leukodystrophy families; screening for low
      enzyme levels among psychiatric populations; and studies in model systems.
      Whereas the basic postulate of an increased risk for psychiatric problems among
      individuals with lower levels of the enzymes deficient in the leukodystrophies
      remains attractive, there is no strong evidence in its support. Low enzyme levels
      can be found in psychiatric populations, but they may not be any more frequent
      than in the general population.

PMID- 1982781
TI  - Current approaches to the genetics of coronary heart disease (CHD) including an
      account of work done at Hammersmith Hospital.
AB  - Genetic variability makes a significant contribution to CHD in Western
      populations. The major genetic component in CHD in the general population is
      polygenic; only a small fraction of the total genetic contribution is due to rare
      monogenic disorders such as FH. Two approaches to the investigation of the
      genetics of CHD are described. In the first, the frequencies of the alleles at
      polymorphic sites in the apoB gene were compared in unrelated normal and CHD men.
      There was a positive association between CHD and two of the alleles investigated
      (E- and X-). The significance of these findings is discussed. In the second
      approach, patients with a clinical diagnosis of FH were screened for the presence
      of a rare mutation in the apoB gene giving rise to defective LDL particles. The
      mutation was detected in 3-4% of the screened population. This suggest that the
      apoB mutation may produce a clinical syndrome indistinguishable from FH.

PMID- 1982782
TI  - Selected papers from the tenth annual conference on peritoneal dialysis. Dallas,
      Texas, February 1990.

PMID- 1982783
TI  - A low CA++ level in effluent as a risk factor for the peritonitis in CAPD
      patients.
AB  - In vitro, some studies revealed the importance of the CA++ level in peritoneal
      macrophage functions in CAPD patients. We therefore retrospectively studied the
      relationship between the frequency of peritonitis and the concentration of Ca,
      Ca++, Interferon-r (IFN-gamma), Interleukin-1B (IL-1B) in the Pd effluent.
      Samples were taken during a peritonitis-free period. In a group of patients
      without peritonitis, the mean Ca++ level in the Pd effluent was 2.25 +/- 0.20
      mEq/L, while in the other group with frequent episodes of peritonitis (more than
      one episode per 20 patient-months), the mean Ca++ level in PD effluent was 2.01
      +/- 0.13 mEq/L which was significantly lower than the former (p less than 0.05).
      The mean Ca concentration in Pd effluent was also lower in the group with the
      high frequent peritonitis than the peritonitis-free group, but not significantly.
      The level of IFN-gamma is lower and IL-1B is higher in the group with frequent
      peritonitis than in the peritonitis-free group, although these differences were
      not significant. These evidences suggest that lower Ca++ level in the effluent of
      the frequent peritonitis group may impair the peritoneal macrophage function and
      peritoneal cell-mediated immune function and may increase a risk of the
      peritonitis. These results may offer a new approach for prophylaxis of
      peritonitis in CAPD patients.

PMID- 1982784
TI  - Bacterial peritonitis and beta-2 microglobulin (B2M) production by peritoneal
      macrophages (PM0) in CAPD patients.
AB  - To evaluate the role of bacterial peritonitis in peritoneal macrophage (PMO) Beta
      2 Microglobulin (B2M) production and its relationship with PMO Interleukin-1 (IL
      1) and Leukotriene B4 (LTB4) release we analyzed in 20 CAPD patients (10 with
      peritonitis): 1. in vivo plasma and peritoneal dialysis effluent (PDE) B2M, IL-1
      and LTB4 levels; 2. in vitro B2M, IL-1 and LTB4 release by PMO. Values were
      compared with those seen in the plasma or with peripheral blood monocytes of 30
      hemodialysis (HD) patients (10 treated with Cuprophan-CU-, 10 with
      Polyacrylonitrile - PAN, and 10 with Cellulose Acetate - CA). Results showed that
      in CAPD patients with bacterial peritonitis B2M, IL-1 and LTB4 concentrations in
      the PDE were significantly higher than those seen in CAPD patients without
      peritonitis or in the plasma of HD patients treated with PAN or CA, but were
      similar to those seen in HD patients treated with CU. At the same time, in vitro,
      PMO from CAPD patients with bacterial peritonitis produced more B2M, IL-1 and
      LTB4 than did PMO from CAPD patients without peritonitis or peripheral blood
      monocytes from HD patients treated with PAN or CA. We conclude that in CAPD
      patients bacterial peritonitis is able to induce PMO B2M production, probably via
      a cytokine-mediated process, which may be analogous to what occurs with
      peripheral blood monocytes of HD patients treated with CU.

PMID- 1982785
TI  - Peritoneal dialysis fluid (PDF) C++ and 1,25(OH)2D3 modulate peritoneal
      macrophage (PM0) antimicrobial activity in CAPD patients.
AB  - Our previous in vitro studies have shown that Ca++ and 1,25(OH)2D3 modulate
      peritoneal macrophage (PMO) antimicrobial activity in CAPD patients. We thus
      evaluated in vivo in 24 CAPD patients (12 who had never had peritonitis and 12
      with an overall peritonitis incidence of more than one episode per 8
      patient/month), the effects of different peritoneal dialysis fluid (PDF) Ca++
      concentrations (1.25, 1.75 and 2.25 mmol/L) on PMO: 1. cytoplasmic Ca++
      concentration; 2. superoxide generation; 3. Leukotriene B4 (LTB4) release; 4.
      bacterial killing for staphylococcus epidermidis. The same parameters were also
      evaluated after adding 1,25(OH)2D3 (0.25 microgram/L) to the PDF. Results showed
      a direct correlation between the PDF Ca++ concentration and PMO Ca++ levels,
      superoxide and LTB4 generation, and bacterial killing, such that with 2.25 mmol/L
      of Ca++ these values were significantly higher than those seen with 1.75 mmol/L.
      The addition of 1,25(OH)2D3 potentiated the Ca++ - induced effects. On the
      contrary, with PDF Ca++ levels of 1.25 mmol/L, an inhibition of the
      aforementioned parameters was seen. However, this effect was reversed by the
      addition of 1,25(OH)2D3. These in vivo results confirm the importance of Ca++ and
      1,25(OH)2D3 in PMO antibacterial functions in CAPD patients and may be useful in
      the prophylaxis and therapy of peritonitis.

PMID- 1982786
TI  - Serial peritoneal macrophage function studies in CAPD patients with peritonitis.
AB  - Continuous ambulatory peritoneal dialysis, peritoneal macrophage, IL-1, IFN-r,
      TNF, phagocytosis. Peritoneal macrophages (PM) perform first-line defense
      activity against peritonitis, the most important complication in CAPD therapy.
      Our longitudinal study compared the PM function in 14 patients in a low
      peritonitis occurrence group (LPOG) and 6 in a high peritonitis occurrence group
      (HPOG) before and during peritonitis; all started CAPD therapy after January
      1988. The results show that at the onset of peritonitis, PM function including
      bactericidal killing (BA) activity, phagocytosis index (PI), H2O2 release,
      interleukin-1 (IL-1) and tumor necrosis factor (TNF) secretion can increase
      rapidly in the LPOG. However, this was absent in the HPOG. Both groups had a
      decrease of PM immunological function in the initial 7 to 10 days after onset of
      peritonitis, then PM functions began to return toward their pre-peritonitis
      state. However, in the HPOG, the recovery of PM function was very slow, resulting
      in significantly lower PM functions. In vitro, when normal PM were put into
      peritonitis dialysate, IL-1, TNF production and PI, BA activity of PM were
      decreased. This suppressor activity was absent in the peritonitis-free dialysate.
      These results suggest a suppressor factor(s) in the HPOG peritoneal dialysate may
      decrease the function of PM rather than cause easy peritonitis development.

PMID- 1982787
TI  - Peritoneal macrophages from patients on CAPD show an increased capacity to
      secrete interleukin-1 beta during peritonitis.
AB  - The in vitro release of interleukin-1 beta (IL-1 beta) by peritoneal macrophages
      from CAPD patients was studied during 16 infection free periods (16 patients) and
      13 episodes of peritonitis (10 patients) using an ELISA. Without exogeneous
      stimulation with LPS, peritoneal macrophages released the same amounts of IL-1
      beta. irrespective if they were obtained during an infection free period (473 +/-
      92 pg/ml 24h, means +/- SEM) or during peritonitis (324 +/- 125 pg/ml). However,
      in response to a dose of 5 micrograms/ml of LPS, peritoneal macrophages released
      significantly more (p less than 0.005) IL-1 beta during peritonitis (6155 +/-
      1743 pg/ml). These findings show that during peritonitis, peritoneal macrophages
      are primed in vivo to release more IL-1 beta in vitro after stimulation with LPS,
      indicating that activation of peritoneal macrophages for IL-1 beta secretion
      occurs stepwise.

PMID- 1982788
TI  - Efficacy of vancomycin plus tobramycin as antiperitonitis regimen for patients on
      CAPD.
AB  - From October 1985 to August 1989, 55 episodes of peritonitis were treated with
      intraperitoneal (i.p.) use of Vancomycin (V) and Tobramycin (T), in 35 patients
      (18 males, 17 females). After three rapid IL peritoneal exchanges, the pts
      received i.p. loading dose of V500 mg/L and an intramuscular dose of T 1.7 mg/Kg,
      followed by four IL exchanges, with addition of V15 mg/L and T8 mg/L. The length
      of treatment was 10 days for all pts. The continued administration of V or T as
      the simple antibiotic regimen was based on the antibiogram, while the combination
      of both antibiotics was used in negative cultures. Recurrence of peritonitis was
      seen in 3 episodes (5.4%). No side effects were seen during the therapy. These
      results indicate that the i.p. use of Vancomycin plus Tobramycin are an
      appropriate antiperitonitis regimen in the treatment of CAPD peritonitis.

PMID- 1982789
TI  - Oral treatment of CAPD-peritonitis with ciprofloxacin.
AB  - Peritonitis is still a major problem in CAPD. The synthetic chemotherapeutic
      quinolone ciprofloxacin offers new possibilities for oral treatment of this
      complication. The efficacy of ciprofloxacin as first-line antibiotic was
      investigated in five consecutive peritonitis episodes of five patients. The
      dosage was deduced from a pilot study and consisted of an intra-peritoneal
      loading dose during the first 24 hours. Simultaneously ciprofloxacin was given
      orally and thereafter only the oral medication was continued. The causative
      microorganisms in the 5 episodes were (MIC90 in brackets): nonfermentative Gram
      negative rod, group IVc-2 (0.6 micrograms/ml), S. aureus (0.25 micrograms ml),
      Strep. faecalis (0.4 micrograms/ml), S. aureus + S. epidermidis (both 0.25
      micrograms/ml) and S. aureus (0.13 micrograms/ml). The clinical course was
      uncomplicated and all episodes were cured with ciprofloxacin monotherapy. In 4
      patients all dialysate concentrations exceeded 2.3 micrograms/ml (mean 5.8
      micrograms/ml). In one patient dialysate concentrations varied between 2.2 and
      7.5 micrograms/ml during the first 24 hrs and between 0.4 and 1.2 micrograms/ml
      thereafter. Despite these low dialysate concentrations, the episode caused by S.
      aureus (MIC90 0.25 micrograms/ml) was cured uneventfully. We conclude that
      ciprofloxacin may be useful for the treatment of CAPD peritonitis. Large
      interindividual differences in dialysate concentrations should be taken into
      account.

PMID- 1982790
TI  - How does peritoneal dialysis remove small and large molecular weight solutes?
      Transport pathways: fact and myth.
AB  - The overall exchange characteristics of the peritoneal 'membrane' are similar to
      those of continuous microvascular walls in general. The capillary walls in the
      peritoneum appear to be the principal structures determining the blood-peritoneal
      exchange.

PMID- 1982791
TI  - Staphylococcus aureus exit-site and tunnel infection in CAPD.
AB  - Fifty-six S. aureus episodes of catheter exit-site tunnel infections were
      diagnosed in 40 out of 163 patients treated by CAPD for 30 +/- 22 months, with
      standard double-cuff Tenckhoff catheters. The rate of infection was 1 episode
      every 29 patient/months. Local care and antibiotic therapy were effective in 52%
      of the cases. Whereas in 29 episodes in which the medical therapy failed to
      eradicate the infection the entire area of granulation tissue and cellulitis was
      excised then the outer dacron cuff was shaved from the silicone catheter. With
      this treatment 13 episodes (48%) were cured while, in the remaining 14 patients
      the catheters were removed because of peritonitis in 10; and for failure to
      eradicate the infection in 4.

PMID- 1982792
TI  - Recurrent peritonitis need not be a cause of CAPD dropout.
AB  - Though excessive peritonitis is reported as the cause of 27% of CAPD dropout,
      over a five-year period, only 5 of 41 patients (12%) who had 5 or more episodes
      of peritonitis stopped CAPD because of excessive peritonitis. Their average time
      on CAPD prior to stopping was significantly longer than other dropouts with less
      peritonitis. Only one patient technically could not continue PD. We conclude that
      excessive peritonitis need not be a major cause for CAPD dropout.

PMID- 1982793
TI  - Incidence and spectrum of organisms causing peritonitis in HIV positive patients
      on CAPD.

PMID- 1982794
TI  - Further experience with the Delmed Freedom Set and the Flush Drain/Fill
      sequencing.
AB  - Presented in February 1989 from this program was data that reflected our
      departure from the then recommended procedure of Drain/Flush/Fill sequencing with
      the Delmed Freedom Set. Our procedure was changed to the now accepted
      Flush/Drain/Fill sequencing in this Y-configured, manual disconnect system. The
      improvement in the incidence of peritonitis was reflected in the data that
      demonstrated 1 episode of peritonitis (EOP)/12.4 patient months with the
      Drain/Flush/Fill (D/F/F) sequencing and the improved incidence of 1 EOP/30.4
      patient months Flush/Drain/Fill (F/D/F). Presented here is the cumulative data
      with an additional 144 patient months experience with the F/D/F sequencing of the
      Delmed Freedom Set and its Safelock connectology. The incidence of peritonitis
      remains relatively low, and not significantly different from that initial 1 year
      data, being 1 EOP/29.6 patient months (current) vs. 1 EOP/30.4 patient months (1
      year data).

PMID- 1982795
TI  - Can we obtain a further reduction of peritonitis episodes in CAPD patients
      already using a Y-set with disinfectant?
AB  - A protocol of patient selection and more frequent home visits have significantly
      reduced peritonitis episodes in CAPD patients using Y-set with Amuchina. However,
      no change in dropout rates were observed.

PMID- 1982796
TI  - Follow-up study to assess line changes with peritonitis.
AB  - Most centers change the transfer set each time a patient develops peritonitis.
      The underlying rationale is that development of intraluminal biofilm may favor
      the adherence of microorganisms to the transfer set and reinfect the patient. The
      purpose of this study was to assess the necessity of a line change with each
      episode of peritonitis. We examined 63 consecutive episodes of peritonitis which
      occurred over a period of 58 months in 23 of our CAPD patients. Each patient
      performed 3 to 4 exchanges per day. Two patients used the Abbott sterile
      connection device, the remainder used a Baxter system. In 33 of these episodes a
      line change was performed (group A) and in 30 it was not (group B). The follow-up
      period after each episode of peritonitis was 4 weeks. There were 3 episodes of
      relapsing peritonitis (same organism within 4 weeks of termination of antibiotic
      treatment) at 3 weeks after finishing intraperitoneal antibiotic therapy in group
      A and no episodes of relapsing peritonitis in group B. In conclusion, according
      to our data it appears that a line change may not always be necessary for the
      adequate management of peritonitis in CAPD patients.

PMID- 1982797
TI  - Clinical experience with alumina ceramic transcutaneous connector to prevent skin
      exit infection around CAPD catheter.
AB  - To prevent skin-exit infection, an important CAPD complication, we developed a
      transcutaneous connector made of Alumina ceramic. The new connector could be
      downsized, because an Alumina ceramic is characteristically bio-inert, rigid and
      non-porous. Our animal experiments with Alumina ceramic in soft tissue
      demonstrated the outstanding bio-compatibility of this material. The shape of the
      new transcutaneous connector was of simple cylindrical configuration so as to
      inhibit macrostress beneath the skin. To make contact with this connector in the
      body, a silicon tube was made into a Swan-necked catheter with a disk-shaped
      polyester cuff, which was positioned subcutaneously beneath the transcutaneous
      connector in order to reinforce adhesion to soft tissue. The silicon tube itself
      was L-shaped in its outside portion just before reaching the connector. We are
      now using this new transcutaneous connector made of Alumina ceramic on a CAPD
      catheter in 8 patients. In the longest case of a patient using it, there has been
      no skin-exit infection for 12 months. Also, there has been virtually no
      downgrowth phenomenon in the skin around the connector, and the connector and
      tissue have remained in very close contact, although fibrous connective tissue
      has been seen to form in the area.

PMID- 1982798
TI  - Tissue reaction to deep cuff of Tenckhoff's catheter and peritonitis.
AB  - To define the type of reaction around the deep cuff of Tenckhoff catheters and
      possible implications in peritonitis development, a histological evaluation of
      the tissue reaction around and into the deep cuff was done. Eight catheters,
      functioning for 2 to 40 months and removed for various reasons were studied. In
      all cases foreign body granulomata and fibrosis were found, with prominent giant
      cell formation. An inert birefrigent material, probably dacron particles, was
      found surrounded by giant cells in fibrotic regions and in some cases appearing
      as cytoplasmic inclusions. In 6 cases an inflammatory infiltration was observed,
      while in 4 with relapsing peritonitis, polymorphonuclears and microabscesses were
      also found. It can be suggested that the tissue reaction to deep cuff predisposes
      to local infections and might be a factor for relapsing peritonitis.

PMID- 1982799
TI  - Reposition of a displaced peritoneal catheter: the Helsinki whiplash method.
AB  - Dialysate outflow obstruction caused by displacement of the catheter tip is a
      relatively common complication of peritoneal dialysis, occurring in up to 20% of
      implanted catheters and often requiring surgical intervention. We describe a
      simple method used to reposition straight, Tenckhoff-type catheters. The
      procedure is performed under fluoroscopic control using a 2 mm thick catheter
      guide, bent fo form a slight curve. The catheter guide is introduced near the tip
      of the migrated catheter and then rotated in order to bring the catheter to the
      pelvis. Experiences over the five-year period 84-89 are summarized. In more than
      60% of the patients, the first displacement occurred within one month of
      insertion of the catheter, and 70% of the catheters migrated to the right. The
      procedure was used in 21 patients to treat 50 displacements. In 86% of the cases
      the procedure was successful. 52% of the patients needed only one reposition
      while 48% experienced two or more displacements and subsequent repositions. Five
      patients eventually needed replacement of the catheter or were permanently
      switched to hemodialysis. The reposition procedure was practically free of
      complications.

PMID- 1982800
TI  - Moist heat intraluminal disinfection of CAPD connectors.
AB  - A moist heat technique for disinfecting the inner lumen of commercially available
      connectology used in the exchange process for Continuous Ambulatory Peritoneal
      Dialysis (CAPD) was evaluated. Moist heat was generated by a device (PDM-1) that
      directed microwave energy to heat a sample solution containing a concentration of
      10(6) microorganisms inside a pair of mated plastic CAPD connectors.
      Microorganisms tested included those most prevalent and most problematic in
      causing peritonitis. Testing, performed according to F.D.A. approved standards,
      involved heating a sample solution and then placing the sample solution into
      vials which were then sealed and incubated. Absolute determination of growth
      versus no growth was measured by macroscopic observation. Positive control
      samples were performed in the same manner but were not exposed to heat. Negative
      controls were performed in the same manner in the absence of test organisms. At
      temperatures of approximately 100 degrees C a D-value of 6.6 seconds was
      determined using the organism found the most thermoresistant. A cycle time of 54
      seconds appeared sufficient to achieve a 10(6) population reduction of all
      microorganisms tested. The moist heat technique offers a safe, effective method
      for disinfection of the inner lumen of CAPD connectors.

PMID- 1982801
TI  - Endoscopic diagnosis of catheter trouble in CAPD patients.
AB  - In case of CAPD catheter trouble, we applied a new diagnostic approach using
      industrial fiberoptics. This method was safe and useful to specify the causes of
      the catheter trouble.

PMID- 1982802
TI  - Defining adequacy of CAPD with urea kinetics.
AB  - The purpose of this paper is to explore the validity of applying urea kinetic
      indices to CAPD. According to the peak concentration hypothesis, the values of
      Kt/V required for adequate dialysis are lower for CAPD than for hemodialysis
      because of the continuous steady state nature of CAPD. Pilot clinical studies
      were undertaken in 19 patients to correlate the (Kt/V)urea index with clinical
      assessment of adequacy based on a 12 parameter score. The data shows that the
      correlation between serum urea nitrogen (Kt/V)urea and protein catabolic rate
      (PCR) are in keeping with the theoretical predictions of the urea kinetic model.
      PCR and dietary protein are well correlated. Also, PCR and Kt/V had a high degree
      of positive correlation. Serum creatinine was inversely correlated with
      (Kt/V)creatinine. In 74% of the patients, the clinical assessment of adequacy was
      in agreement with the (Kt/V)urea domains of adequacy established from the peak
      concentration hypothesis and the urea kinetic model. The lack of correlation in
      the remaining 26% is being investigated.

PMID- 1982803
TI  - Application of urea kinetic modeling to adequacy of CAPD therapy.

PMID- 1982804
TI  - Urea kinetic analysis and clinical outcome on CAPD. A five year longitudinal
      study.
AB  - The present study, along with some recent studies, suggests that there is an
      organic link between the amount of dialysis a patient receives and his/her
      nutritional status. The latter, as reflected by serum albumin, is predictive of
      survival on CAPD. It is clear, therefore, that urea kinetic analysis is a
      powerful tool for prescribing and monitoring therapy in CAPD patients.

PMID- 1982805
TI  - PET--a simpler approach for determining prescriptions for adequate dialysis
      therapy.
AB  - Fast Pet test is a modified version of original PET. Only one dialysate sample
      for glucose and creatinine is taken from the total drained dialysate and a blood
      sample at the end of the test exchange. It can be used both for diagnostic and
      prognostic purposes. The Pet and clearance measurements are complementary studies
      which can guide in dialysis prescription.

PMID- 1982806
TI  - Net ultrafiltration volume (nUFV) during IPD with acetate or lactate dialysis
      solutions.
AB  - There is debate as to how much acetate in PD solutions influences the nUFV, so we
      decided to evaluate it during uncomplicated IPD and aseptic peritonitis connected
      with IPD treatment. In 8 patients dialysed with acetate (35 mmol/L) solutions for
      9 +/- 8 months the nUFV (drainage volume minus instillation volume, mL/exchange)
      was calculated for 1.5 and 4.25% glucose exchanges during uncomplicated IPD and
      aseptic peritonitis. Then, lactate (35 mmol/L) buffered solutions were used
      instead of acetate ones and the nUFV was estimated under the same conditions.
      During uncomplicated IPD as well as peritonitis the nUFV was significantly higher
      in exchanges with lactate then with acetate solutions when the glucose
      concentration were comparable. In aseptic peritonitis the nUFV was less decreased
      with lactate than acetate solutions. We conclude during uncomplicated IPD or
      aseptic peritonitis in patients dialysed with acetate buffer the nUFV can be
      improved when acetate in PD solutions is substituted by lactate.

PMID- 1982808
TI  - Is the peritoneal membrane durable indefinitely?
AB  - In general, the permeability characteristics of the peritoneal membrane are well
      maintained with time in the context of current technique survival rates. Some
      data would suggest that there is a tendency toward hyperpermeability in long-term
      PD patients; in a much smaller group of patients this may manifest itself as a
      loss in ultrafiltration capacity in the short term, that is within 2-4 years
      after CAPD initiation. A reduction in factors, which continue to have a
      significant negative effect upon technique survival, such as peritonitis and
      catheter-related infection will see patients remaining on the therapy for longer.
      This may place a sharper focus on ultrafiltration loss in the PD population,
      particularly that associated with increases in the permeability of the
      peritoneum. However, until such time as significant improvements occur it is
      likely the peritoneal membrane will continue to be more durable than the therapy
      in the vast majority of patients. It is now becoming clearer that the rate of
      decline of residual renal function (RRF) may be an important factor in the
      development of sequelae associated with inadequate dialysis. The role of RRF has
      often been overlooked when the clinical manifestations of inadequate UF and
      solute removal have become apparent and further study is required to determine
      the contribution of residual diuresis to the table of prognostic factors
      associated with long-term stability of the PD patient. Nevertheless, it is
      clearly an important parameter worthy of considerable future focus. Although
      membrane performance appears well maintained in general, routine monitoring of
      the mass transfer performance of the peritoneum should be performed. Assessment
      will facilitate focussed dialytic management and allow the clinician to recognise
      and pre-empt potential problems resulting from inadequate dialysis associated
      with decreasing or increasing membrane permeability in the small number of
      patients so affected: such monitoring should include measurement of the mass
      transfer coefficient at onset and every 6-12 months thereafter. However, the
      monitoring of RRF and overall solute clearance is perhaps of more significance in
      view of the contribution of RRF to overall dialytic prescription. The routine
      assessment of these parameters is also encouraged.

PMID- 1982807
TI  - A method to assess efficacy of CAPD: preliminary results.
AB  - Adequacy of dialysis is a primary concern when caring for patients undergoing
      continuous peritoneal dialysis (CAPD). To determine objectively the efficacy of
      CAPD, the use of an 'efficacy number' (EN) calculated from the data obtained in a
      peritoneal equilibration test (PET) for creatinine (cr) is proposed: EN =
      [cr(D/P) x V24] divided by ACPPD3 Where, cr(D/P) is PET-derived dialysate/plasma
      ratio for creatinine at 4 hrs; V24 is the volume of exchanges (L) prescribed for
      24 hrs; ACPPD is adjusted creatinine production based on daily dialysate
      creatinine appearance. PET were performed and the EN calculated in two groups of
      CAPD patients observed over a 10 month period. One group (n = 8) had a poor
      clinical outcome in terms of uremic parameters. The EN in this group was 3.85 +/-
      0.45 (+/- 1 SD) L/g creatinine/day. The other group (n = 4) was considered well
      dialyzed and had a good clinical outcome over 10 months. The EN in this group was
      6.07 +/- 0.40 L/g creatine/day, p less than 0.001. There was no statistically
      significant difference between the two groups in regard to sex, age, length of
      time on dialysis, underlying kidney disease, baseline creatinine, or D/P ratios
      of creatinine and BUN. The 'efficacy numbers' appears to be more useful than the
      D/P ratio alone in determining the adequacy of CAPD. A simple to use nomogram is
      presented which provides guidelines for the clinician to alter the dialysis
      prescription.

PMID- 1982809
TI  - Serum sodium concentration and plasma renin activity in CAPD patients.
AB  - Hyponatremia is not uncommon in patients on CAPD, despite the presence of an
      intraabdominal solution that should preserve normal serum sodium concentration.
      We have examined the relationship between the plasma renin level and serum sodium
      concentration in our CAPD patients. Patients with abnormal causes for increased
      thirst were removed from the study; that is, diabetic patients with fluctuating
      blood sugar or patients on tricyclic antidepressants or clonidine. In forty-one
      patients a statistically significant inverse correlation between serum sodium and
      plasma renin levels was demonstrated. We conclude that thirst stimulation by the
      renin-angiotensin system contributes to the hyponatremia seen in many patients on
      CAPD.

PMID- 1982810
TI  - Erythrocyte Na-stimulated Mg transport in uremic patients undergoing CAPD.
AB  - A derangement of magnesium homeostasis with hypermagnesemia and increased
      intraerythrocyte Mg content [Mgi] has been described in uremic patients, and
      could play a pathogenetic role in both alterations of bone metabolism and
      vascular reactivity, observed in these patients. Recently Feray and Garay
      described in human erythrocytes a transport system which catalyzes outward Mg
      movements in the presence of external Na. These fluxes may be responsible for
      maintaining and regulating a low [Mgi]. The aim of this study was to evaluate in
      16 normal subjects and 14 uremic patients undergoing CAPD: [Mgi] and rate of Na
      dependent and Na-independent Mg efflux in Mg-loaded erythrocytes, in order to
      maximally stimulate Mg efflux. Mean plasma and intraerythrocyte Mg concentrations
      were significantly higher in CAPD than in normal subjects (1.09 +/- 0.20 vs 0.86
      +/- 0.004 mmol/l, p less than 0.001 and 2.57 +/- 0.38 vs 1.96 +/- 0.18 mmol/l
      RBC, p less than 0.001). After an in-vitro Mg load, the intraerythrocyte Mg
      concentration and Na-independent Mg efflux were similar in both groups (17.5 +/-
      1.4 vs 18.2 +/- 4.1 mmol/l RBC and 152 +/- 20 vs 126 +/- 19 mumol/l RBC/h).
      However, the Vmax of erythrocyte Na-stimulated Mg efflux was significantly higher
      in CAPD patients than in normal subjects (357 +/- 48 vs 229 +/- 88 mumol/l RBC/h,
      p less than 0.02). [Mgi] and the rate of Na-dependent Mg efflux were inversely
      related in CAPD patients (r = -0.76; p less than 0.002). These results indicate
      that uremic CAPD patients have a [Mgi] and Vmax of erythrocyte Na-dependent Mg
      efflux higher than normal subjects; this could reflect a compensatory, although
      insufficient, mechanism against high levels of intraerythrocyte Mg concentration,
      as suggested by the correlation between [Mgi] and the rate of Na-dependent Mg
      efflux.

PMID- 1982811
TI  - Intraindividual comparison of ANP, cGMP and plasma catecholamines between HD and
      CAPD.
AB  - Patients with end stage renal failure have elevated plasma levels of atrial
      natriuretic peptide (ANP) which seems to be a sensitive parameter of body fluid
      status. A prospective study comparing patients on hemodialysis (HD) and
      continuous ambulatory peritoneal dialysis (CAPD) was still missing. Six identical
      patients (59 +/- 10 yrs, residual diuresis 1.3 +/- 0.61, 1 data expressed as
      means +/- SEM) were studied in the predialysis phase and under steady state
      conditions on HD and on CAPD. Plasma levels of ANP, cyclic guanosine
      monophosphate (cGMP), adrenaline, noradrenaline and dopamine were determined.
      Blood and dialysate samples were repeatedly taken. Ultrafiltration-volume, dry
      weight and blood pressure were not different between HD and CAPD. ANP and cGMP
      reached the highest plasma levels in the predialysis phase with 421 +/- 180 pg/ml
      and 19.8 +/- 6.4 pmol/ml and decreased after the onset of dialysis treatment. On
      HD mean ANP levels of 279 +/- 175 pg/ml were not significantly different from
      those on CAPD (320 +/- 213 pg/ml). However, cGMP concentrations on CAPD (15.7 +/-
      5.4 pmol/ml) surpassed the values measured on HD (10.5 +/- 3.4 pmol/ml, p less
      than 0.05). Plasma noradrenaline was markedly elevated in the predialysis phase
      (421 +/- 180 pg/ml) and decreased under dialysis treatment. Differences between
      HD and CAPD were not found. Adrenaline and dopamine concentrations fell within
      the normal range.

PMID- 1982812
TI  - Macrophage secretory activity and atherosclerosis during chronic renal failure.
AB  - Accelerated atherosclerosis is a serious complication of chronic renal failure
      (CRF) treated by peritoneal dialysis. In order to study the pathological
      mechanisms underlying its development we are using an animal model, namely the
      C57BL/6J mouse, which develops foam cell-type atherosclerotic lesions after
      surgical induction of CRF. During atherogenesis, monocyte/macrophages move from
      the circulation to the blood vessel wall, migrate through the endothelium, imbibe
      lipid and transform into foam cells. Migration through the endothelium involves
      proteolysis by plasminogen activator (PA) and uptake of lipids involves
      hydrolysis of lipoproteins by lipoprotein lipase (LPL). Both of these enzymes are
      secreted by macrophages. In this paper we report the results of studies on the
      effect of uremia on the secretion of PA and LPL by macrophages from C57BL/6J
      mice. The secretion of PA and LPL by macrophages from uremic mice (as defined by
      BUN levels) was higher than that by cells from control animals. Furthermore,
      whereas macrophage secretion of PA and LPL was significantly less in normal mice
      fed a high fat diet than in mice fed rodent chow, it was increased above control
      levels in uremic animals fed the atherogenic diet. We conclude that increased
      secretion of PA and LPL by macrophages may contribute to atherogenesis in uremic
      C57BL/6J mice.

PMID- 1982813
TI  - Transport of water and solutes in uremic patients with chronic hepatic disease in
      CAPD.
AB  - Ten patients with chronic hepatic disease (CHD) were compared with 34 non-CHD (N)
      pts. All patients underwent a peritoneal equilibration test; the asymptotic
      curves for small solutes transport were transformed into straight lines; protein
      transport was also expressed as a straight line; the slopes of these linear
      functions were used as index of solute transfer. CHD patients showed increased UF
      and transport of all solutes. The well-known relationships between UF and glucose
      absorption and between UF and dialysate sodium concentration were observed in N,
      but not in CHD patients. In patients without hepatic disease there was also a
      relationship between UF and the glucose transport slope, which was not observed
      in CHD pts. These results are probably due to the influence of hepatic lymph
      production plus increased lymphatic removal, observed in non uremic patients
      affected by cirrhosis, on the mechanisms of water and solute transport in CAPD.
      CHD patients can be managed either with CAPD or with short frequent exchanges.
      Ascites production can be evaluated by the difference between the observed UF in
      a patient with CHD and the expected UF in N patients.

PMID- 1982814
TI  - Cell membrane lipid composition in CAPD patients.
AB  - We analyzed the erythrocyte membrane lipid composition in 11 non-diabetic CAPD
      patients on treatment for 3-78 months and in a control group of 12 subjects. The
      mean total values of both saturated fatty acids and unsaturated fatty acids were
      not statistically different in CAPD patients and in controls but the composition
      of fatty acids of in cell membranes was altered. In fact, CAPD patients had a
      higher percentage of monounsaturated fatty acids and a lower percentage of
      polyunsaturated fatty acids than controls. This increase MUFA/PUFA ratio might
      reflect either a preferential cell membrane uptake of MUFA or a relative PUFA
      deficiency due to an increased lipid peroxidation.

PMID- 1982815
TI  - The impact of CAPD treatment on lipid metabolism and cardiovascular risk.
AB  - The metabolism of lipids in CAPD has not been fully elucidated. To further
      clarify the behavior of dyslipidemia in this setting we followed the values of
      total cholesterol (TC), HDL-cholesterol (HDL-C) and apolipoprotein (apo)
      parameters over time (12-24 months) in 40 patients and correlated these values
      and their ratios with clinical (age, gender, race, weight, diabetes, etc.) and
      biochemical (multiphastic screen) information. Mean HDL-C was lower in men (p
      less than 0.04), in whites, (p less than 0.03) and in diabetic patients (p less
      than 0.05), but there were no group differences for mean total cholesterol, mean
      apolipoprotein values, the atherogenic risk ratio TC/HDL-C, or the anti
      atherogenic ratio apo A-I/apo B. Total months on CAPD was found to correlate
      positively with TC/HDL-C (p less than 0.05), an atherogenic risk factor, and to
      correlate negatively with HDL-C (p less than 0.02), an anti-atherogenic index.
      There was also a negative correlation with another anti-atherogenic index, apo A
      I/apo B, which did not reach statistical significance (r = -0.41, p = NS).
      Counterbalancing this apparently increased atherogenic risk is the stability of
      individual parameters for each patient over time in this study. In fact, the good
      news appears to be that TC, HDL-C, apolipoproteins and the risk ratios TC/HDL-C
      and apo A-I/apo B all remained stable over 12-24 months (p = NS by paired t-test
      for all). Thus, we find no evidence for worsening of the uremic dyslipidemia over
      time with CAPD treatment.

PMID- 1982816
TI  - Secondary hyperparathyroidism in CAPD patients: its suppressibility with high
      doses of calcitriol.
AB  - Secondary hyperparathyroidism (HP) is well known complication of long-term
      uremia. CAPD patients show a peculiar behaviour due to loss of vitamin D
      metabolites through peritoneum. Severe degrees of hyperparathyroidism may require
      parathyroidectomy in order to achieve appropriate control. Recently, the
      possibility of controlling this situation with high oral doses of calcitriol has
      been communicated. The purpose of this study is to evaluate the effect of this
      agent on hyperparathyroidism in CAPD patients. Two different groups were
      constituted according to the length of time on dialysis when HP was detected. All
      of the patients had i-PTH serum levels five times higher than the normal values
      (50 pg/ml). During a six month period the daily dose of oral calcitriol was
      increased in order to achieve a reduction in i-PTH level. The results after this
      period showed a significant reduction in i-PTH levels (614 +/- 378 to 241 +/- 80
      pg/ml) with an average increase in oral calcitriol from 0.16 +/- 0.1 to 0.67 +/-
      0.4 with no significant changes in serum calcium or phosphorus. The group with HP
      at start of dialysis achieved these effects easier and with lower doses of
      calcitriol. We conclude that moderately high doses of oral calcitriol control
      secondary hyperparathyroidism in CAPD patients without hypercalcemia.

PMID- 1982817
TI  - The nutritional approach for pediatric patients undergoing CAPD/CCPD.
AB  - The current recommendations for the nutritional management of children treated
      with CAPD/CCPD will be reviewed. The optimal caloric intake for pre-pubertal
      children undergoing dialysis should at least be determined by the recommended
      daily allowances (RDA) of the National Academy of Science for healthy children of
      the same height and age. For pubertal and post-pubertal patients, the prescribed
      energy intake is similar to the RDA for adolescents, 60 kcal/kg for males, and 48
      kcal/kg/day for females. Dietary complex carbohydrates should provide about 35%
      of dietary energy intake. Dietary fat should provide 50% of the dietary intake,
      and the PS:S fatty ratio should be about 1.5:1.0. The recommended protein intake
      for children less than 3 years of age should range between 2.5-3.0 gm/kg/day; for
      children between 3 years of age and puberty 2.5 gm/kg/day; for pubertal patients
      2.0 gm/kg/day, and post-pubertal patients 1.5 gm/kg/day. In general, sodium,
      potassium and water intake vary markedly among patients and should be managed
      individually. Vitamins, folic acid 1 mg/day; peridoxine, B6 5-10 mg/day; and
      ascorbic acid 75-100 mg/day. Vitamin D sterols (i.e., calcitriol) and phosphate
      binding agents mainly calcium carbonate are needed for the prevention and control
      of renal bone disease in such patients. Aluminum containing gels should be
      avoided in order to prevent aluminum accumulation secondary to the ingestion of
      aluminum containing gels.

PMID- 1982818
TI  - Tube feeding in the real world: formulas, equipment, finances, and feeding
      problems.
AB  - When selecting enteral feedings for infants and children on continuous peritoneal
      dialysis care should be taken to meet individual needs to provide for nutritional
      adequacy and normal growth rates. This requires a combination of complete
      feedings plus modules. The feedings should be evaluated frequently to adjust for
      growth and changes in renal function or treatment.

PMID- 1982819
TI  - Tube feeding in children on chronic peritoneal dialysis.
AB  - We feel that tube feeding children on CPD is an important and useful therapy to
      optimize their growth. Strategies to accelerate growth in such children by using
      human growth hormone are interesting and await scientific confirmation with
      controlled trials.

PMID- 1982820
TI  - Measurement of the peritoneal platelet activity through the effluent
      betathromboglobulin levels in CAPD patients.
AB  - Platelet activity is closely related to endothelium and could release factors
      able to influence capillary wall and surrounding tissues. BTG is a protein
      included in platelet vesicles and a measure of its activation. Some alterations
      of peritoneum could be partially related to platelet activity. BTG peritoneal
      transport from blood is weight limited (36000) and consequently, high levels in
      effluent should represent local production. The aim of this study has been to
      characterize peritoneal effluent BTG.12 patients, on CAPD 27 +/- 15 mon., 5
      diabetics were studied. Previous peritonitis was 0.3 +/- 0.4 e/year.
      Determinations performed: Plasma (P) (BTG, T. protein, albumin, platelet count,
      Hcto and Fibrinogen) and Effluent (EF) (BTG, T. protein, Fibrinopeptide A, FDP,
      Fibrinolytic act., Fibrinogen, Plasminogen and Mitogenic induced capacity on
      Swiss 3T3 mice fibroblasts). To evaluate peritoneal function we used mass
      transfer coefficients (MTC) and net UF.R.:BTG levels: P 118 +/- 14 EF 34 +/- 14
      ng/ml P/EF (%) 31 +/- 13 (6-54%). Regression analysis: P BTG did not show
      significant relationship with any of the studied parameters. EF BTG showed direct
      significant correlation (p less than 0.05) with Creatinine-MTC (r: 0.81) and EF
      Fibrinogen (0.68) and in the limit of significance with EF T. prot (0.57) and EF
      Mitogenicity (0.62). P/EF BTF showed significant correlation with creatinine-MTC
      (0.77). The analysis of these values grouping patients showed: diabetes has no
      influence on BTG values, hypertensive patients show higher P/EF BTG values than
      normotensive (39 +/- 9 vs 23 +/- 11%, p less than 0.05) and no influences of
      peritonitis or CAPD period were found.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1982821
TI  - Complications of nasogastric and gastrostomy tube feedings in children with end
      stage renal disease.
AB  - Twelve children with end stage renal disease requiring dialysis received enteral
      feedings via nasogastric (NG) or gastrostomy (G) tube between 1984 and 1989 for
      provision of adequate nutrition. Records were reviewed for frequency and types of
      complications seen. Six patients, ages 1 week to 16 months received NG feedings
      for a total of 32 months. Complications included persistent vomiting with
      recurrent aspiration (2), persistent vomiting with peritoneal dialysis (PD) exit
      site leak (1), sinusitis (1), and refusal to continue NG feeds because of
      patient/parental anxiety (1). Three of the 6 were changed to G tube feedings
      after 2 days to 3 months. The complication rate was 1 per 6.4 patient months.
      Nine patients, ages 4 days to 11 years, received G tube feedings for 64 months.
      The complication rate was similar, 1 per 7.1 months. Complications were PD fluid
      leak around G tube exit site (1), G tube infection (2), G tube obstruction
      requiring tube replacement (3), tube migration producing intestinal obstruction
      (1), and gastrocutaneous fistula (2). Both methods were associated with similar
      complication rates, although somewhat different types of complications were seen.
      The young dialysis patient may have certain unique risks in addition to the
      complications generally associated with enteral feedings.

PMID- 1982822
TI  - Nutritional and behavioural aspects of nasogastric tube feeding in infants
      receiving chronic peritoneal dialysis.
AB  - Eight infants initiated chronic peritoneal dialysis and received nasogastric tube
      feedings during their first month of life. In each case, the nasogastric tube
      feedings were initiated because of poor oral intake and the desire to avert the
      development of an aversive feeding interaction between parent and child. The
      nutritional regimen was designed to allow normal or catch up weight gain
      appropriate for height age. The caloric and protein intake of the infants
      averaged 98.5 +/- 10.2 kcal/kg/day and 2.7 gm/kg/day, respectively, during the
      first year of life. Between 25% and 100% of the formula intake was provided by
      the nasogastric route. Group standard deviation score for height was -1.74 +/-
      0.7 at one year. Five of the infants received behavioral therapy because of
      persistent food refusal. Therapy consisted of reinforcing prompted food
      acceptance and ignoring food refusal. This approach was conducted by a
      multidisciplinary team and successfully converted the non-oral feeder to a total
      oral feeding regimen in each case.

PMID- 1982823
TI  - Growth of small children managed with chronic peritoneal dialysis and nasogastric
      tube feedings: 203-month experience in 14 patients.
AB  - This 203-month experience with CPD and NG feedings in 14 small children weighing
      less than or equal to 10 kg at initiation of CPD for ESRD, provides evidence that
      CPD and vigorous nutritional therapy is effective in maintaining and improving
      growth until a successful renal transplant can be performed. Nutritional therapy
      should be initiated early, if possible when growth begins to decline even before
      the onset of ESRD and the need for CPD. Infants who are less than or equal to 4
      months old at initiation of CPD are more likely to have a complicated clinical
      course and poor growth, despite the provision of CPD and vigorous nutritional
      support. More experience with this group of patients is needed to determine
      appropriate therapy.

PMID- 1982824
TI  - Percutaneous gastrojejunostomy for caloric supplementation in children on
      peritoneal dialysis.
AB  - Experience with percutaneous gastrojejunostomy is described in children on
      chronic cycler peritoneal dialysis. We recommend this mode of enteral
      alimentation for children requiring caloric supplementation.

PMID- 1982825
TI  - Impaired development of oral-motor functions required for normal oral feeding as
      a consequence of tube feeding during infancy.
AB  - The child who is tube fed during the first two years of life is at risk for
      impaired development of normal oral-motor patterns and coordination during
      feeding. In order to ensure as smooth a transition to oral feeding as possible,
      it is necessary to provide the tube-fed child with a framework of normal oral
      sensitization from which he can develop the level of trust in his own oral
      mechanism required to achieve the mature, coordinated oral movements essential to
      development of the normal bite-chew-suck-swallow sequence. While this can be a
      tedious and taxing process, an ongoing program of oral stimulation, training and
      development should be included in the overall management of every young child
      receiving tube feedings.

PMID- 1982827
TI  - Management of a child on CAPD with a ventriculoperitoneal shunt.
AB  - Long term dialysis in children with multiple handicaps has become easier with the
      advent of CAPD. In December 1986, an 11 year old with myelomeningocele in end
      stage renal disease secondary to chronic pyelonephritis required dialysis.
      Placement of a right ventriculoperitoneal shunt had been done at 4 months of age.
      Poor family compliance required placement in medical foster care. The peritoneal
      catheter was replaced three times. Leakage and infection were the major
      complications resulting in catheter replacement. In March 1988 the child required
      shunt extension due to accelerated growth after which she developed relapsing
      peritonitis requiring removal of the peritoneal catheter and externalization of
      the ventriculoperitoneal shunt. A proximal tap of the ventriculoperitoneal shunt
      prior to revision had a negative culture but glucose of 471 when serum glucose
      was 91. Six days after externalization of the shunt and catheter removal, the
      shunt was converted to ventriculoatrial and the PD catheter replaced. Nasogastic
      feedings and cycler dialysis became necessary due to worsening nutritional status
      and hyperabsorption. Successful transplantation occurred 28 months after initial
      dialysis.

PMID- 1982826
TI  - Tegaderm dressings for peritoneal dialysis and gastrojejunostomy catheters in
      children.
AB  - Peritoneal dialysis catheters are at risk for exit-site contamination when
      swimming or bathing. Also in pre-toilet trained children fecal and urine
      contamination can occur. The use of Tegaderm dressings prevents contamination and
      thus minimizes restriction of activity in children.

PMID- 1982828
TI  - Treatment of very young infants with ESRD--renal transplantation as soon as
      possible (less than 1 yr of age): controversy.
AB  - The Pediatric nephrologist is the infant patient's medical advocate, joining with
      the family to efficiently restore renal function and vigor to a child
      incapacitated by renal failure. In this context, renal transplantation, even in
      infancy, is an effective, available therapy holding the potential to improve the
      long term outcome for individual young children.

PMID- 1982829
TI  - Accuracy of erythropoietin determination in the dialysate of CAPD patients.
AB  - In vitro experiments were performed to analyze problems with the determination of
      erythropoietin in dialysate. Human recombinant erythropoietin (EPO; 4000 U/L) was
      added to several fluids, to glass or polystyrene tubes with or without addition
      of bovine serum albumin (BSA) and to dialysate bags. The recovery in peritoneal
      effluent was 4120 +/- 203 U/L (mean +/- SEM). The recovery in the other fluids
      was less than 50% but in glass tubes it increased to 96% after addition of BSA.
      Binding was also found to the dialysate bag, therefore reducing the amount
      available for absorption. We recommend that EPO samples from the dialysate are
      drawn within BSA coated glass tubes.

PMID- 1982830
TI  - Efficacy of recombinant erythropoietin after subcutaneous or intraperitoneal
      administration to patients on CAPD.
AB  - Recombinant erythropoietin (R-EPO) administered i.v. is effective in correcting
      anemia in patients on hemodialysis (HD). As subcutaneous (s.c.) or
      intraperitoneal (i.p.) dosing would be preferable in CAPD patients, we have
      evaluated its efficacy when given by these routes. Sixteen CAPD patients (mean Hb
      7.3 +/- 1.6 g/dl) have been divided into two groups: group A received s.c. self
      administered R-EPO (starting dose 92 +/- 35 U/kg/week) two times a week; in group
      B R-EPO was given i.p. (170 +/- 42 U/kg/week) thrice weekly. The observation
      period lasted about 12 months. All patients reached a target Hb greater than 10
      g/dl. Group A achieved a full response within 9 +/- 2 weeks, group B within 13 +/
      1.7 (p less than 0.005). In group A the starting R-EPO dose was not changed; in
      group B it was increased to 225 +/- 45 U/kg/week. We observed no differences in
      the incidence of peritonitis in the two groups. Our findings show that both R-EPO
      administration routes are safe and efficient in correcting anemia in patients on
      CAPD. A shorter period of treatment and lower doses of R-EPO seem to be required
      to achieve the same target Hb level when using the s.c. rather than the i.p.
      application route.

PMID- 1982831
TI  - Treatment of the anemia with human recombinant erythropoietin in CAPD patients.
AB  - Three homogenous groups of CAPD patients, all of them with plasma hemoglobin
      levels lower than 8 g/dl were studied. Group 1 included 8 patients who received
      EPO by the subcutaneous route (s.c), at doses of 20 u./kg daily; this dose was
      reduced when a hemoglobin level higher than 10.5 g/dl was reached. Group 2
      included 7 patients treated with EPO by subcutaneous route but at doses of 2000
      units twice a week. Group 3 was constituted by 4 patients receiving EPO by
      intraperitoneal route (i.p.), at doses of 4000 u/day, three days a week. All
      patients showed an increase in hematocrit and Hb levels after three months of
      treatment, but the mean EPO dose was quite different comparing the groups,
      maintaining the reached levels at the 9th month; reticulocyte count increased
      only during the first month. The rest of clinical and biochemical parameters did
      not suffer any significant modifications. Our features showed a higher profit,
      that is, higher increase in Hb level with lower dose of EPO in the s.c. group in
      respect to i.p. group. Furthermore, we have registered a marked increase in the
      frequency of exogenous peritonitis in these particular patients while using i.p.
      EPO. In conclusion, we feel that subcutaneous route for H-R-Erythropoietin is an
      ideal way for this treatment, resulting in a more adequate profit ratio than that
      described in hemodialysis patients. The intraperitoneal route is more expensive
      and risky for the peritoneum, probably as a consequence of the increase of
      manipulations.

PMID- 1982832
TI  - Categorization of ultrastructural changes in peritoneal mesothelium, stroma and
      blood vessels in uremia and CAPD patients.
AB  - This paper presents an interim report on the findings of the International
      Peritoneal Biopsy Registry (IPBR). The registry was set up for the collection and
      morphological examination of specimens of peritoneal tissue obtained at surgical
      implantation or removal of the catheter before, during or after treatment with
      continuous ambulatory peritoneal dialysis (CAPD). The key objective of the
      Registry is the accumulation of information on the effect of peritoneal dialysis,
      peritonitis and any other complication of the therapy, on the structural
      integrity of peritoneal mesothelium, stroma and blood vessels.

PMID- 1982833
TI  - One year experience with subcutaneous human erythropoietin in CAPD: correction of
      renal anemia and increased ultrafiltration.
AB  - After 6 months of (recombinant human erythropoietin) rHuEPO treatment we recently
      observed an increased peritoneal ultrafiltration (UF) (Nephron 53: 91, 1989). The
      aim of the present study was to investigate the long term effect of subcutaneous
      (SC) on dialysis efficiency in CAPD. Fourteen patients (11 female, 3 male, mean
      age 42.6, range 18-65 years) with renal anemia (HCT less than 28%) took part in
      the study. rHuEPO was administered s.c. twice weekly in an initial dose of 50
      U/kg body weight. This dose was increased by 25 U/kg body weight every 4 weeks
      till the target HKT of 35% had been achieved. After 12 months of mean time of
      treatment (range 8-14 months) hematocrits had increased from 23.3 +/- 3.2 (x +/-
      SD) to 36.6 +/- 5.3% (p less than 0.005). UF improved from 0.70 +/- 0.22 to 1.03
      +/- 0.47 ml/min (4 hr dwell time, 1.5% glucose monohydrate) (p less than 0.03).
      Increased UF resulted in an augmented creatinine clearance (p less than 0.05). No
      changes were observed in serum chemistries, body weight, pulse rate or
      cardiothoracic index. The observed increase in peritoneal ultrafiltration might
      be due to augmented mesenteric perfusion resulting from improved cardiac
      function. The sustained increase in UF after rHuEPO-induced correction of renal
      anemia may improve the fluid balance on CAPD patients.

PMID- 1982834
TI  - Treatment of anaemia in CAPD patients with recombinant human erythropoietin.
AB  - EPO is an effective therapy of anaemia in CAPD patients. Monitoring serum iron
      level during EPO therapy is essential. Hypertension is frequently seen in
      patients with EPO therapy.

PMID- 1982835
TI  - Clearance of branched chain amino acids by peritoneal dialysis in maple syrup
      urine disease.
AB  - Thirty-eight hours of peritoneal dialysis (PD) was used in an 8-day-old, 3.35 kg
      boy with maple syrup urine disease (MSUD) to enhance the removal of branched
      chain amino acids (BCAA). PD clearances for leucine, isoleucine, and valine were
      3 ml/min/1.73 m2, compared to urinary clearances of 0.16 ml/min/1.73 m2 (0.4
      ml/min/1.73 m2 for isoleucine). The augmented clearance was reflected by a faster
      rate of fall in the plasma leucine level during dialysis (38 microM/hr) than
      before or immediately after dialysis (10 microM/hr). The biochemical improvement
      was accompanied by neurologic improvement in the baby. Once the leucine level
      fell to below 1500 mu + M, the unaugmented rate of fall for leucine (21
      microM/hr) was similar to that augmented by PD. Our experience demonstrates that
      PD is useful for enhancing clearance of BCAA at leucine levels greater than 1500
      microM and that it speeds neurologic recovery.

PMID- 1982836
TI  - Ca++ and 1,25(OH)2D3 regulate in vitro and in vivo the response to human
      recombinant erythropoietin in CAPD patients.
AB  - In vitro studies indicate that the culture medium Ca++ concentration conditions
      the response to erythropoietin of bone marrow erythropoietic cells which also
      have specific receptors for 1,25(OH)2D3. We therefore evaluated in 12 anemic CAPD
      patients: 1) in vitro with increasing concentrations of Ca++ alone or Ca++ plus
      1,25(OH)2D3 a) Ca++ in the bone marrow erythroid cell cytoplasm; b) colony (BFU-E
      and CFU-E) growth from bone marrow erythroid cells. 2) in vivo before and after
      24 weeks of i.v. recombinant human erythropoietin (rHuEPO) therapy a) bone marrow
      erythroid cell cytoplasmic Ca++; b) BFU-E and CFU-E growth. Results showed that
      in CAPD patients, in vitro cytoplasmic Ca++ in bone marrow erythroid cells, and
      BFU-E and CFU-E growth were lower than in normals and the addition of Ca++ caused
      a dose-dependent increase; 1,25(OH)2D3) potentiated these effects; 2, in vivo
      rHuEPO therapy normalized the aforementioned parameters. An inverse relationship
      was seen between the bone marrow erythorid cell cytoplasmic Ca++ levels before
      therapy and the duration of therapy necessary to correct anemia. These data
      underline the role of Ca++ and 1,25(OH)2D3 in erythropoiesis in uremic patients
      and may aid the understanding of the mode of action and the degree of response to
      rHuEPO in CAPD patients.

PMID- 1982837
TI  - Changes of peritoneal membrane function during long-term CAPD.
AB  - Peritoneal equilibration tests (PETs) in patients on CAPD show wide variations.
      To find out whether these are correlated with time on CAPD, we investigated
      changes in PET in 97 tests in 86 patients. 46 PETs were performed with a 1.36%
      glucose solution and 40 PETs with a 3.86% glucose solution at different time
      intervals. Neither did the intra-individual comparison of 11 patients with 1.36%
      glucose solution following 1 year of treatment show any significant change nor
      the inter-individual comparison following a treatment time of 1 and 2 years.
      There was also no difference using a 3.86% glucose exchange, when the results at
      the beginning and after 1 year were compared. However, alterations in
      equilibration ratios were significant after 24 and 36 months of treatment for
      creatinine (36 months versus 0: p less than 0.005), glucose absorption (36 months
      versus 0: p less than 0.01) and UF (36 months versus 0: p less than 0.01). No
      correlation exists between these changes either with the number of peritonitis
      episodes or with the time of treatment. Though, no single factor could be
      identified, patients had an increase in peritoneal permeability especially after
      long-term treatment. Further investigations are necessary to evaluate the reasons
      for these changes.

PMID- 1982838
TI  - Peritoneal dialysis glossary III.

PMID- 1982839
TI  - Diabetic patients on CAPD need less aluminum hydroxide as a phosphate binder than
      non-diabetics.
AB  - A retrospective study was done in 86 patients on dialysis in order to evaluate
      the doses of aluminum hydroxide (OH3 Al) received to achieve a better serum
      phosphate control. Thirty-seven patients were treated with continuous ambulatory
      peritoneal dialysis (CAPD) divided in 22 diabetics and 15 non-diabetics. Forty
      nine patients were treated with hemodialysis (HD), 12 diabetics and 37 non
      diabetics. The doses of 1-25 Dihidroxycholecalciferol (1-25 DOH-D3) were similar
      in all patients. The serum phosphate levels were similar in CAPD and HD patients
      with smaller doses of OH3 AL in CAPD patients (p less than 0.001). Diabetics on
      either technique need less OH3 AL in CAPD (CAPD p less than 0.01; HD p less than
      0.05) to achieve the same or better control of serum phosphorus than non
      diabetics. The overload of glucose on CAPD and the maintained hyperglycemia on
      diabetes mellitus would shift phosphorus into the cell and could explain these
      results. Finally, the less needs of aluminum hydroxide on diabetic patients could
      contribute to their protection against aluminum deposition and its effects.

PMID- 1982840
TI  - CAPD in diabetics: use of aminoacids.
AB  - Advantages of CAPD in diabetic uremic patients may offer better control of visual
      and neurological disease. There remain some undesired side effects, i.e: obesity,
      blood lipid imbalance and loss of appetite due to glucose absorption. In February
      1988 four diabetic uremic CAPD patients (2 males and 2 females with an average
      age of 62.25 +/- 11.32, range 52-76) began treatment substituting one of the
      usual glucose exchanges with 1% aminoacid solution. Treatment time averaged 52
      months (range 9-17). Each month the patients were examined clinically and via
      blood chemistries. Every 3 months clearances, residual renal function, ocular
      fundus and motor nerve conductance velocity were measured. Plasma nitrogen
      increased, while triglycerides, cholesterol and total protein remained unchanged;
      bicarbonate decreased causing slight acidosis. There were no significant
      variations of either clearances or ultrafiltration and the quantity of insulin
      administered decreased. Results confirm that a 1% aminoacid solution can be used
      as an osmotic agent in peritoneal dialysis to prevent some of the complications
      such as blood lipid imbalance. The slight acidosis can be corrected by increasing
      the buffer content of the bag.

PMID- 1982841
TI  - Vascular disease: the critical risk factor for mortality in older patients on
      CAPD.
AB  - Clinical course, complications and outcome were analyzed in 75 patients (14
      women, 61 men) who started CAPD at age 55 years or older (55-81). These patients
      were separated in three groups. Group A patients had high risk for vascular
      disease (diabetes, hypertension, N = 45), group B patients had a presumed lower
      risk for vascular disease (primary renal disease, N = 22), and group C patients
      had miscellaneous conditions (N = 8). Group A was compared to group B. Patient
      and technique survival was statistically higher for group B than for group A. The
      rates of peritoneal dialysis related complications (peritonitis, tissue
      infections, catheter loss, hernias) were comparable between groups A and B.
      Hernias were seen frequently in all groups and had severe sequellae, including
      discontinuation of CAPD. Catastrophic vascular events were also seen in all
      groups, but the frequency of such events, particularly of catastrophic vascular
      events of the limbs, was statistically higher in group A than in group B.
      Vascular disease accounted for the majority of deaths in all groups. Four
      patients died from cardiovascular instability soon after changing from CAPD to
      hemodialysis. In conclusion, vascular disease is the major factor limiting
      survival in older CAPD patients. CAPD is superior to hemodialysis for a
      relatively small fraction of older patients with severe cardiovascular
      instability.

PMID- 1982842
TI  - Peritoneal x-ray and computerized tomography in evaluating abdominal
      complications in CAPD.
AB  - CAPD is a widely accepted therapy, however, some patients develop complications
      that can impede continued therapy. Peritonitis is the most critical problem. A
      series of complications require accurate examination to avoid discontinuing
      necessary therapy, i.e.: leakage, inguinal and ventral hernia, trauma, catheter
      malfunction and scrotal-penile edema. For the past few years we have used
      peritoneal x-ray to evaluate these complications. Recently we have included
      computerized tomography with intraperitoneal contrast. We have studied 20
      patients since 1985. The empty peritoneal cavity is filled with 100 cc of
      iopamidol, a non-ionic, low osmolality contrast, containing 300 mg of iodine/ml.
      No complications were ever encountered during or after these studies. The method
      has proven most useful in therapeutic decisions permitting, very often,
      continuing peritoneal dialysis. The results are extremely reliable due to its
      simplicity and the complete absence of complications.

PMID- 1982843
TI  - Early and late peritoneal dialysate leaks in patients on CAPD.
AB  - Dialysate leaks, which occurred in 386 CAPD patients over 11 years, were analyzed
      retrospectively. 18 patients developed 21 early leaks (within 30 days of catheter
      insertion) and 18 patients developed 28 late leaks (beyond 30 days of catheter
      insertion). 8 patients had multiple (2-6) leaks. Both early and late leaks,
      particularly if they were multiple, were associated with conditions that affect
      adversely tissue healing and tensile strength. Median surgical insertion was
      apparently associated with a higher incidence of early leaks. Early leaks were
      manifested externally, usually through the exit site, and did not require
      imaging. Late leaks were manifested usually by poor dialysate outflow, localized
      edema and subcutaneous fluid collections. One third of the late leaks required
      radiological imaging. Hernias caused 42% of the late leaks. Early leaks were
      managed by temporary discontinuation of CAPD alone (57%) or surgery. Most late
      leaks (67%) required surgery. Conservative means (change to IPD, observation)
      were applied for the management of a few late leaks. Both early and late leaks
      resulted frequently in replacement of peritoneal catheters, but only late leaks
      resulted in permanent discontinuation of peritoneal dialysis. Paramedian surgical
      insertion, waiting period of 10-14 days between catheter insertion and initiation
      of CAPD, and low starting dialysate volumes have resulted in apparent reduction
      of the incidence of the early, but not of the late leaks. Dialysate leaks have
      serious consequences on the performance of CAPD. Early leaks differ from late
      leaks in some clinical manifestations. Preventive measures have decreased the
      incidence of early, but not of the late leaks.

PMID- 1982844
TI  - Comparison between two dialytic populations undergoing renal transplantation.
AB  - The outcome of renal transplantation in CAPD patients is still controversial
      since age and clinical differences often make comparison with hemodialysis
      patients difficult. The aim of this study was to analyse two homogeneous groups
      of patients, on CAPD and on hemodialysis. 18 CAPD (Group A) and 18 hemodialysis
      patients (Group B) were selected for a case-control analysis, matched for age,
      presence of acute tubular necrosis and Cyclosporine A regimen. Group A and B were
      not different for male/female ratio, donor age, HLA-Dr mismatches, arterial
      pressure, cold ischemia, or follow-up. Patient, graft survival and number of
      rejection episodes did not differ significantly at 1 year; serum creatinine at 6
      and 12 months and CyA doses at 1 and 6 months were not different; hospitalization
      rates for first and subsequent admissions did not differ. Infection-free patients
      were 9/18 in Group A and 15/18 in Group B, with 12 episodes in Group A and 3 in
      Group B. Post transplant cholesterol levels showed a trend to increase in both
      groups and triglycerides levels to a decrease; differences in pre and post
      transplant in body weight were not significant at 12 months. In conclusion, the
      outcome of transplantation in CAPD patients is not significantly different from
      that in hemodialysis patients with similar clinical characteristics.

PMID- 1982845
TI  - Feasibility of in-center staff-assisted cycler dialysis.
AB  - Many debilitated elderly patients are not currently considered for peritoneal
      dialysis because they cannot perform the procedure themselves and they lack
      adequate back-up support in the family or extended care facility. They often
      tolerate hemodialysis poorly, and may exhaust their vascular access sites. We
      have provided intermittent in-center staff-assisted cycler dialysis to two
      debilitated elderly patients for a total of 12 patient months. Initial peritoneal
      equilibration tests indicated high solute transport rates in both patients, and
      led us to evolve a regimen based on frequent cycles. We use a 4 days a week
      regimen, cycling 12-14 liters during a 7.5 hour period each day. The patients
      tolerated the treatment well, with improved control of fluid balance and
      maintenance or improvement in appetite compared to baseline periods of CAPD. Mean
      pre-treatment BUN is 87 mg/dl. This is 29% higher than during CAPD, and has been
      stable. The requirement for additional nursing care has been variable but not
      disruptive of other activities once we established a dedicated space and routine.
      Current cycler technology permits consideration of in-center cycling as a
      practical alternative for many patients previously excluded from peritoneal
      dialysis.

PMID- 1982846
TI  - Sclerosing peritonitis complicating continuous ambulatory peritoneal dialysis
      with the use of chlorhexidine in alcohol.
AB  - Sclerosing peritonitis (SP) is an uncommon but serious complication of CAPD with
      various suggested etiology. We have documented 14 cases of SP in 18 CAPD patients
      using chlorhexidine in alcohol (ChA) in the connection procedure; 13 died. Nine
      of the 14 patients had been transferred to haemodialysis or renal
      transplantation, yet all still developed symptoms of SP within a few months after
      transfer even though 5 of them were originally asymptomatic. The main symptoms of
      SP were peritoneal ultrafiltration failure, exudative bloody ascites and
      intestinal obstruction. They present at around 5 years (30-80 months) after
      commencement of CAPD. Four other patients with a comparable duration of ChA
      exposure were continued on CAPD with a Travenol Spike System (TSS) without
      further exposure to ChA. They were all asymptomatic of SP after 9-12 months.
      Comparing the 2 groups of asymptomatic patients at 9 months after transfer, those
      transferred to TSS have a much better outcome than those transferred to HD or
      renal transplantation (P = 0.0476). We concluded that ChA is the main cause of SP
      in our patients and continuing CAPD without further exposure to ChA is a better
      alternative than stopping CAPD in preventing the progression of SP.

PMID- 1982847
TI  - Do peritoneal dialysis providers experience burnout?
AB  - The Maslach Burnout Inventory (MBI) was used to determine whether peritoneal
      dialysis (PD) providers experience burnout. The questionnaire was completed by 55
      physicians, 277 nurses and 4 other PD providers who attended the 9th Annual
      Conference on Peritoneal Dialysis. Our results show that burnout experienced by
      PD providers is comparable to that experienced by other providers in the medical
      field. Specific variables such as single martial status, full time employment and
      additional hemodialysis responsibilities were also identified as factors that may
      be associated with high degree of burnout.

PMID- 1982848
TI  - A multi-center study: clinical practices of HIV infected patients on CAPD/CCPD.
AB  - Our statistics reveal the average patient in our study to be a young black male
      with a history of IVDA with CAPD as the initial dialysis modality. He was most
      often trained on a mechanical assist device, but he still developed frequent
      peritonitis episodes, predominantly gram positive. His survival rate was less
      than 2 years, but he was able to remain independent until he died. Our fears
      about caring for the HIV infected individual cannot be denied. Even though we may
      never be truly comfortable when caring for someone with this disease, it is
      possible to train them to perform home peritoneal dialysis safely and
      effectively. By doing this, we can preserve the patients' independence and
      maintain their dignity while they cope with this overwhelming illness.

PMID- 1982849
TI  - Are peritoneal host defenses really important?
AB  - Peritonitis requires a constant focus of infection plus the presence of foreign
      material, both amply present in the CAPD patient with an indwelling catheter and
      universal bacterial biofilm. Amazingly the great variety of potentially cytotoxic
      and immunodiluent agents with which the CAPD peritoneum is confronted on a daily
      basis does not produce the gross rate of sepsis that might be predicted. Clearly
      the profound reserve capacity of the peritoneal defense mechanisms, whose
      functions and interactions are poorly described and understood, contribute to the
      continuing success of the CAPD modality.

PMID- 1982850
TI  - Clinical significance of peritoneal dialysate IgG levels in CAPD patients.
AB  - To assess the normal range and the clinical significance of peritoneal IgG, the
      levels of these proteins were measured in 24 hour dialysates of 69 patients. The
      mean + SD of IgG levels was 7.2 +/- 4.3 mg/dl. Two patients had peritoneal IgG
      concentrations below and 6 above the mean +/- SD range. There were no significant
      correlations between peritoneal IgG levels and sex, previous hemodialysis, age,
      time of dialysis, number of peritonitis or estimated daily protein intake. In 29
      of these patients dialysate IgG levels measured again one year later did not show
      significant differences between the first and the second determination of IgG
      (from 6.3 +/- 3.3 to 6.6 +/- 3.2 mg/dl), but changes of 10% or more were observed
      in 14 of these patients. Our data show no relation between peritoneal IgG and
      peritonitis episodes. Therefore by these results dialysate IgG cannot be used as
      a reliable index to decide which patients are at high risk for peritonitis.

PMID- 1982851
TI  - Molecular genetics of primary intracranial tumors.

PMID- 1982852
TI  - Bone marrow transplantation in the treatment of lymphoma.

PMID- 1982853
TI  - Recessive mutations in the oncogenesis of certain solid tumors.

PMID- 1982854
TI  - Dystonia--a potential psychiatric pitfall.
AB  - The manifold presentations of dystonia have been acknowledged as a spectrum of
      illness. Dystonia is primarily idiopathic or drug-induced; purely psychogenic
      causes would seem to be rare, although such an aetiology is commonly assumed.
      Response to medication in idiopathic cases is unpredictable, although
      anticholinergic medication and behavioural programmes are being evaluated.

PMID- 1982855
TI  - Aggressiveness, anxiety and drugs.

PMID- 1982856
TI  - How to treat gastroesophageal reflux in children.

PMID- 1982857
TI  - [Hemodynamic effects of the cold pressor test in patients with heart failure
      treated with beta blockers for a long time].
AB  - In congestive heart failure (CHF) the beta-adrenoceptor density and functional
      responsiveness is markedly reduced presumably due to endogenous down-regulation.
      In the last few years evidence has accumulated that betablockers therapy can
      improve clinical condition in selected patients with CHF. To evaluate sympathetic
      response in CHF we measured hemodynamic effects of cold pressor test. This study
      was composed by 20 patients, 10 with CHF of different origin and 10 healthy
      volunteers. They were divided into 4 groups in relation to therapy. We evaluated
      the modification of the following hemodynamic parameters during cold pressor
      test: heart rate, mean arterial pressure, mean pulmonary arterial pressure,
      pulmonary capillary wedge pressure, right atrial pressure, cardiac index,
      systemic vascular resistance, pulmonary vascular resistance. In normal subjects
      we observed hemodynamic modification of heart rate, mean arterial pressure and
      systemic vascular resistance according to many other Authors. In atenolol-treated
      subjects the sympathetic response is strongly attenuated. Patients with CHF not
      treated with betablockers showed an increase in heart rate and in systemic
      vascular resistance and a reduction of cardiac index. Chronic treatment with
      atenolol did not modify heart rate response to cold pressor test. The mean
      arterial pressure increased while the systemic vascular resistance did not show
      any significant modification. We observed a trend to increase of the cardiac
      index; this could explain the beneficial effect of betablockers therapy in
      selected patients.

PMID- 1982858
TI  - [Derivatives of para-hydroxyacetophenone and para-hydroxypropiophenone as a
      potential new beta-adrenolytic agent].
AB  - Within the framework of the study of the structure-effect relationship, a series
      of novel potential beta-adrenolytic agents derived from p-hydroxyacetophenone and
      p-hydroxypropiophenone with an alyloxymethyl and a cycloalkyloxymethyl group in
      the lipophilic part of the molecule and an isopropyl and a tert-butyl group in
      the hydrophilic part on the basic nitrogen were prepared by means of a well-tried
      method. The structure of the prepared drugs was confirmed on the basis of
      interpretation of the IR, UV, 1H-NMR and mass spectra. The results of
      pharmacological evaluation of selected drugs show that the agents poses beta
      adrenolytic and antiarrhythmic activity. From the viewpoint of comparison of the
      individual drugs subjected to testing the presence of an alyl seems more
      advantageous than that of a cyclohexyl. The characteristic of the prepared drugs
      was supplemented by the determination of their partition coefficients, surface
      tension and acute toxicity.

PMID- 1982859
TI  - [Restriction fragment length differences (RFLDs) of genomic DNA from different
      geographical strains of Anopheles sinensis and Anopheles anthropophagus].
AB  - Total DNA was extracted from three geographical strains of Anopheles sinensis and
      two geographical strains of Anopheles anthropophagus and digested respectively
      with three restriction endonucleases (Bgl II, Hae III and Pst I). The restriction
      fragment length differences (RFLDs) of repetitive DNA detected after agarose gel
      electrophoretic separation and ethidium bromide staining were compared among the
      above-mentioned geographical strains of both An. sinensis and An. anthropohagus.
      The results indicated that the band patterns are species- specific and strain
      specific, their main bands being similar while their minor bands being distinctly
      different. Pst I digestion produced unique fragments for three geographical
      strains of An. sinensis while Bgl II digestion produced unique fragments for two
      geographical strains of An. anthropophagus. In view of the variation in
      repetitive DNA of different geographical strains of both An. sinensis and An.
      anthropophagus presented, the RFLDs could be used as a means to distinguish
      various closely related geographical strains of anopheline mosquitoes.

PMID- 1982860
TI  - [Application of DNA recombination technique to parasitological research].

PMID- 1982861
TI  - Graves' disease following hypothyroidism due to Hashimoto's disease: studies of
      eight cases.
AB  - Hashimoto's and Graves' diseases represent the main two types of autoimmune
      thyroid disease. The combination of these two is well known. However, occurrence
      of Graves' disease after primary hypothyroidism is rare. We report seven patients
      with hypothyroidism due to Hashimoto's disease, who developed Graves' disease
      with hyperthyroidism. We also report one patient with hypothyroidism due to
      Hashimoto's disease, who continued to be hypothyroid even in the presence of TSAb
      (thyroid stimulating antibody). These patients were divided into three groups
      according to the changes in thyroid function and clinical course: (1) transient
      hyperthyroidism due to Graves' disease following hypothyroidism; (2) persistent
      hyperthyroidism due to Graves' disease following hypothyroidism; and (3)
      persistent hypothyroidism with positive TSAb. Such changes in thyroid function
      and clinical course seem to be decided by three factors: (1) TSAb and (2) TSBAb
      (thyroid stimulation blocking antibody) activities in the blood and (3) the
      responsiveness of the thyroid gland to TSAb. Seven patients had hyperthyroidism,
      when they had TSAb, which stimulated the thyroid gland; one of these seven
      patients had TSBAb during the hypothyroid state and TSAb during the hyperthyroid
      state, indicating that the alterations in the thyroid state related to the
      balance between the activities of TSAB and TSBAb. Another patient continued to be
      hypothyroid despite the presence of TSAb; his thyroid gland was not palpable and
      could not respond to TSAb.

PMID- 1982862
TI  - Follow-up study of thyroid stimulating-blocking antibodies in hypothyroid
      patients.
AB  - It has been shown that hypothyroidism of some patients may be associated with
      increased activity of thyroid stimulating-blocking antibodies (TSBAb). The
      present study was undertaken to follow the course of thyroid blocking,
      stimulating immunoglobulins and TSH-binding inhibitor immunoglobulins (TBII) in
      six hypothyroid patients who had elevated TSBAb and were treated with T4. Four of
      the six had Graves' disease previously treated with antithyroidal drugs, one had
      Graves' disease treated with 131I and one had subacute thyroiditis and
      subsequently became hypothyroid. The patients were followed for 1-5 years.
      Blocking activity and TBII normalized in four of the six during T4 therapy, so T4
      was discontinued and they remained euthyroid. These data indicate that it is
      important to monitor carefully thyroid function in hypothyroid patients treated
      with a fixed amount of T4 to avoid subclinical hyperthyroidism and its
      consequence, e.g. osteoporosis.

PMID- 1982863
TI  - The responses of arginine vasopressin and adrenocorticotrophin to nausea induced
      by ipecacuanha.
AB  - Ipecacuanha syrup induces emesis by an early peripheral (gastric irritant) action
      and a later central effect at the chemoreceptor trigger zone (CTZ). We have
      studied the responses of plasma AVP, ACTH and ACTH-precursors to early and late
      ipecacuanha-induced nausea in nine healthy male subjects. Symptom severity was
      assessed using a linear analogue scale. All subjects reported 'early' nausea (N1)
      with a latency of 16 +/- 2 min (mean +/- SEM) and eight subjects vomited. Six
      subjects experienced recurrent nausea (N2) (latency 106 +/- 10.4 min) of whom
      five also vomited. The interval between the cessation of N1 and the onset of N2
      was 55 +/- 10.8 min (range 25-80 min). The severity of nausea at the onset of N1
      or N2 was similar but the AVP and ACTH responses were highly variable. Thus,
      while mean plasma AVP concentrations increased during both symptom periods, in
      three subjects during N1 and in three subjects during N2 plasma AVP
      concentrations did not rise above the normal range, despite marked symptoms. No
      clear pattern of AVP response to distinguish early peripheral from late central
      ipecacuanha-induced emesis was demonstrated. Whilst mean plasma ACTH
      concentrations increased during both N1 and N2 there were no changes in mean
      plasma ACTH-precursor concentrations. Analysis of pooled data for N1 and N2
      demonstrated direct correlations between the nausea score and the peak
      incremental plasma responses of either AVP or ACTH and, despite the variability,
      peak incremental concentrations of AVP and of ACTH were also correlated. The data
      indicate that there is no difference in the AVP responses to peripherally or
      centrally stimulated ipecacuanha-induced nausea.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1982864
TI  - Screening for multiple endocrine neoplasia type 1 in patients with recognized
      pituitary adenoma.
AB  - A total of 79 consecutive patients with pituitary tumours were screened for
      multiple endocrine neoplasia type 1 (MEN-1). The 79 patients included 21 patients
      with acromegaly, nine with Cushing's disease, 18 with prolactinomas, three with
      mixed pituitary adenomas (GH and PRL), and 28 patients with no detectable
      hypersecretion of hormones. The screening consisted of: (1) a family history, (2)
      a uniform medical history of the patient using a standard questionnaire, and (3)
      hormonal evaluation including measurements of the serum levels of insulin,
      gastrin, glucagon, somatostatin, vasoactive intestinal polypeptide and pancreatic
      polypeptide. Ionized calcium and glucose concentration in serum were also
      measured. We found no patients with the MEN-1 syndrome. In one patient, we found
      a transient elevation of serum concentrations of pancreatic polypeptide for which
      we have no explanation. In another patient, the serum gastrin concentration was
      elevated secondary to achlorhydria. No other endocrine disorders were found, and
      no patients had relatives with recognized endocrine pancreatic tumours, primary
      hyperparathyroidism (HPT), or pituitary adenomas.

PMID- 1982865
TI  - Isolation and characterization of hemorrhagic metalloproteinase from Vipera berus
      berus (common viper) venom.
AB  - 1. Hemorrhagic metalloproteinase (HMP) was isolated by gel filtration on a
      Sephadex G-100 (superfine) and affinity chromatography on agarose HPS-7. 2.
      Hemorrhagic metalloproteinase is a glycoprotein with mol. wt 56.3 kDa. It
      contains 1 zinc atom per molecule of protein. 3. Hemorrhagic metalloproteinase
      hydrolyzes casein, fibrinogen and splits the insulin B chain at positions Ala14
      Leu15, Tyr16-Leu17, His10-Leu11. It digests A alpha chain of fibrinogen.

PMID- 1982866
TI  - In vitro estimation of non-specific and specific amino acid decarboxylase
      activities in guinea-pigs treated with chlorpromazine.
AB  - 1. In vitro studies of non-specific histidine decarboxylase activity was low or
      absent in control guinea-pigs and unchanged 9 or 27 hr after chlorpromazine (CPZ)
      injection intraperitoneally. 2. However, specific histidine decarboxylase
      activity was found in the control tissues and was increased 9 hr but not 27 hr
      after CPZ injection.

PMID- 1982867
TI  - Radioactive uptake of [14C]histamine by certain tissues in guinea-pigs treated
      and untreated with chlorpromazine.
AB  - 1. Oral administration of [14C]histamine induced the presence of small amounts of
      [14C]histamine in stomach and ileal tissues of control guinea-pigs. In contrast,
      much larger amounts were found after 8 h infusion. 2. Similar amounts of
      [14C]histamine were found in the tissues when [14C]histamine was given by
      intravenous infusion from 24-30 h after chlorpromazine injection.

PMID- 1982868
TI  - Distribution of NADPH-diaphorase positive cells in the rat brain.
AB  - 1. Recent work suggests that neurones in vivo and in culture which contain
      neuropeptide Y and somatostatin and which stain positively for the enzyme NADPH
      diaphorase may be resistant to excitotoxins. 2. We have therefore examined the
      distribution of the enzyme throughout the rat brain. 3. Neurones were found
      intensely or moderately stained at all levels of the neuraxis, but with
      particularly dense clusters of cells in the periaqueductal grey area and dorsal
      raphe nucleus of the hindbrain, the pedunculopontine and interpeduncular nuclei,
      and the dorsal spinal trigeminal nucleus. 4. Intensely stained cells occurred
      with no clear pattern in neocortical and striatal areas, and in nucleus basalis.
      5. The observed distribution of staining is consistent with previous studies in
      other species of limited regions of the CNS. 6. While no consistent functional or
      neurochemical correlate of the NADPH-diaphorase distribution could be proposed,
      the work provides a basis for more detailed investigations of neuronal
      sensitivity to excitotoxins.

PMID- 1982869
TI  - Glutamate dehydrogenase: some properties of the rat brain enzyme from different
      cellular compartments.
AB  - 1. Differences in the GDH activity of neuronal, glial cells and synaptosomes were
      detected. 2. The enzyme was measured in both directions: synthesis and
      degradation of glutamate. 3. Synaptosomes were the region with the highest GDH
      activity. 4. ADP plays an important role in the regulation of the reaction sense.
      5. This effector produced higher activation on the enzyme measured in the
      direction of glutamate synthesis than in the sense of its degradation. 6. The
      enhancement produced by ADP was dependent on the enzyme localization. The ADP
      effect is discussed.

PMID- 1982870
TI  - Iodoacetic acid-induced rigor in ileal longitudinal smooth muscle of guinea-pig.
AB  - 1. Ileal tensions to iodoacetic acid (IAA) develop when tissue ATP concentration
      falls below approximately 60-55% of the control. 2. As the IAA concentration is
      increased (0.1-10 mM), the ATP concentrations decrease rapidly, and both the time
      of the onset and the duration of the contraction shorten. 3. In the presence of
      lactate, IAA failed to decrease the tissue ATP concentration and did not develop
      tension. 4. The contraction to IAA developed in the presence of Ca2+ antagonist,
      D-600 or in Ca2(+)-free solution, however, onset time was prolonged. 5. These
      results suggest that the contraction to IAA is referred to as 'rigor' because it
      increases with decreasing tissue ATP concentration in ileum.

PMID- 1982871
TI  - The action of dopamine receptor antagonists on the secretory response of the
      cockroach salivary gland in vitro.
AB  - 1. A study has been made of the potency of a number of dopamine antagonists to
      inhibit dopamine-induced secretion from the cockroach salivary gland in vitro. 2.
      Chlorpromazine (0.5-5 microM), SCH23390 (10-100 microM), haloperidol (10-100
      microM) and metoclopramide (2 mM) competitively inhibited the secretory response
      to dopamine. In contrast (+/-)sulpiride (1-100 microM) and domperidone (1-100
      microM) had no effect on either basal or dopamine-induced secretion. 3. Apparent
      dissociation constants (KDapp) were obtained using a 'three point assay'. The
      rank order of potency (KDapp in parentheses) was as follows: chlorpromazine (0.2
      microM) greater than SCH23390 (2.2 microM) greater than haloperidol (17.5 microM)
      much greater than metoclopramide (1.2 mM). 4. It is concluded that the receptor
      mediating dopamine-induced secretion in the cockroach salivary gland is similar
      to the D1/DA1 dopamine receptor and distinct from the D2/DA2 receptor found in
      mammalian systems.

PMID- 1982872
TI  - Use of the fish enzyme system in monitoring water quality: effects of mercury on
      tissue enzymes.
AB  - 1. Rosy barb (Puntius conchonius) were exposed to 181 micrograms/l mercuric
      chloride for 48 h and the activity of acid and alkaline phosphatases (AcP and
      AIP), aspartate aminotransferase (AAT), alanine aminotransferase (AIAT), lactic
      dehydrogenase (LDH), and acetylcholinesterase (AchE) were measured in vivo in
      several organs. 2. The AcP activity was inhibited in the liver, gills, kidneys,
      and gut but stimulated in the gonads. With the exception of kidney, the AIP
      activity showed an increase in all the organs examined. The AAT and AIAT were
      generally inhibited in different organs. An increase in LDH activity occurred in
      the cardiac and skeletal muscles while the AchE activity was considerably lowered
      in the brain, gills, and liver. 3. In vitro exposure to mercury at concentrations
      ranging between 10(-10) and 10(-4) M, inhibited the AIP, AAT, AIAT, LDH, and AchE
      activities in the tissues examined. The AcP activity was also depressed in all
      the tissues except in the testes, in which a marginal increase was noted. 4. The
      in vivo and in vitro effects of Hg were not of similar quality implying
      sequestration of toxic cations in the intact animals.

PMID- 1982873
TI  - Comparative study of the edema-inducing activity of snake venoms.
AB  - 1. The edema-inducing activity of 24 venoms from snakes of the subfamilies of
      Elapinae, Hydrophiini, Crotalinae and Viperinae was determined. 2. All snake
      venoms tested are very potent edema inducers. The minimum edema doses of the
      venoms ranged from 0.16 to 3.41 micrograms per mouse paw. 3. The venoms induced a
      rapid onset edema which peaked within 1 h of injection and declined thereafter;
      at low dose, however, some venoms induced a rapid onset edema that sustained over
      a longer duration.

PMID- 1982874
TI  - Vascular smooth muscle relaxation by endothelium-dependent beta 1-adrenergic
      action.
AB  - 1. Norepinephrine (NE) (10(-5) M) in rabbit aorta relaxed ring segments with
      endothelium precontracted with 10(-6) M NE, but not segments without endothelium.
      2. The relaxation was inhibited with metoprolol and methylene blue, but not
      inhibited with yohimbine and indomethacin. 3. NE (10(-5) M) significantly
      elevated tissue c-GMP levels in segments with endothelium. 4. These studies
      suggest that the vascular relaxation by high doses of NE is mediated by the
      release of endothelium-derived relaxing factor (EDRF) induced by the stimulation
      of beta 1-adrenoceptor.

PMID- 1982875
TI  - Analgesic effects of D-amino acids in four inbred strains of mice.
AB  - 1. Prominent strain differences of mice were found in analgesic effects of D
      amino acids. 2. In C57BL/6CrSlc and C3H/HeSlc mice, pain threshold, which was
      determined by using a hot-plate method, increased to 140-175% of the control
      after the systemic treatment of all three D-amino acids employed, such as D
      phenylalanine, -leucine and -methionine, whereas in DBA/2CrSlc or BALB/cCrSlc
      mice, out of three only one D-amino acid, D-phenylalanine or -leucine, produced
      significant increase of pain threshold. 3. This lack of ability to perceive
      analgesic effects of specific amino acids observed in the latter two strains
      suggests that there probably exist different analgesia-inducing mechanisms for
      each of three D-amino acids in mice and the latter two strains lack two of them.

PMID- 1982876
TI  - A sialidase from the hepatopancreas of the shrimp Penaeus japonicus (Crustacea:
      Decapoda): reversible binding with the acidic beta-galactosidase.
AB  - 1. The sialidase purified from the hepatopancreas of Penaeus japonicus is able to
      bind the acidic beta-galactosidase in vitro. No protective protein, Mr 32,000,
      was detected in either purified enzyme preparation. 2. The specific activity of
      the isolated sialidase is 55.0 mU/mg of protein. After polyacrylamide gel
      electrophoresis under denaturing conditions, the purified shrimp enzyme was found
      to consist of monomers of Mr 32,000. 3. The sialidase from shrimp has an
      isoelectric point (pI) of 4.6 +/- 0.1. 4. The shrimp enzyme has the pH optimum at
      5.0 and its Km was 5.5 microM with 2'-(4-methylumbelliferyl)-alpha-D-N
      acetylneuraminic acid as substrate. The enzyme activity was inhibited by either
      Hg2+ or Cu2+ ions.

PMID- 1982877
TI  - Effects of domestic wastewater on serum enzyme activities of brown trout (Salmo
      trutta).
AB  - 1. Chronic injuries of kidney and liver tissue of brown trout caused by domestic
      wastewater were not accompanied by increased activities of serum enzymes (GOT,
      GPT). 2. Increased enzyme activities were only observed in fish with acute
      Saproloegnia infection. 3. It is important to distinguish between acute and
      chronic responses of serum enzymes in diseased fish.

PMID- 1982878
TI  - Cardiac and splenic levels of norepinephrine and dopamine in copper deficient
      pigs and rats.
AB  - 1. Copper deficiency decreased the concentration and content of norepinephrine in
      the hearts of pigs and rats. 2. Concentration, but not content, of norepinephrine
      was decreased in spleen of copper-deficient pigs, while splenic norepinephrine
      levels in rats were not altered by copper deficiency. 3. Cardiac and splenic
      concentrations and contents of dopamine were elevated in copper-deficient pigs
      and rats. 4. Tissue concentrations of catecholamines and the magnitude of change
      due to copper deficiency were greater in pigs than rats.

PMID- 1982879
TI  - Increased susceptibility to transglutaminase of eye lens proteins exposed to
      activated oxygen species produced in the glucose-glucose oxidase reaction.
AB  - In order to test whether a mild oxidative stress could promote the
      transglutaminase damaging effect on eye lens proteins, total lens soluble
      proteins and purified beta L-crystallin have been exposed to H2O2 slowly produced
      by the glucose-glucose oxidase reaction. Soon after the pretreatment, the
      substrate capacity of the lens proteins for an exogenous transglutaminase has
      been evaluated. Exposure to the oxidative stress increased the susceptibility of
      the lens proteins to transglutaminase. When ferrous ions were added to the
      preincubation medium, in order to convert the H2O2 into the hydroxyl radical, the
      increase was more evident.

PMID- 1982880
TI  - Genetic polymorphisms of drug metabolism.
AB  - The molecular mechanisms of 3 genetic polymorphisms of drug metabolism have been
      studied at the level of enzyme activity, enzyme protein and RNA/DNA. As regards
      debrisoquine/sparteine polymorphism, cytochrome P-450IID6 was absent in livers of
      poor metabolizers; aberrant splicing of premRNA of P-450IID6 may be responsible
      for this. Moreover, 3 mutant alleles of the P-450IID6 locus on chromosome 22
      associated with the poor metabolizer phenotype were identified by Southern
      analysis of leucocyte DNA. The presence of 2 identified mutant alleles allowed
      the prediction of the phenotype in approximately 25% of poor metabolizers. The
      additional gene-inactivating mutations which are operative in the remainder of
      poor metabolizers are now being studied. Regarding mephenytoin polymorphism,
      although the deficient reaction, S-mephenytoin 4'-hydroxylation, has been well
      defined in human liver microsomes, the mechanism of this polymorphism remains
      unclear. All antibodies prepared to date against cytochrome P-450 fractions with
      this activity recognize several structurally similar enzymes and several cDNAs
      related to these enzymes have been isolated and expressed in heterologous
      systems. However, which isozyme is affected by this polymorphism is not known. As
      regards N-acetylation polymorphism, N-acetyltransferases have been purified from
      human liver, specific antibodies prepared; it was observed that immunoreactive N
      acetyltransferase is decreased or undetectable in liver of "slow acetylators".
      Two genes that encode functional N-acetyltransferase were characterized. The
      product of one of these genes has identical activity and characteristics as the
      polymorphic liver enzyme. Cloned DNA from rapid and slow acetylator individuals
      has been analyzed to identify the structural or regulatory defect that causes
      deficient N-acetyltransferase.

PMID- 1982881
TI  - The effects of alprazolam, quazepam and diazepam on saccadic eye movements,
      parameters of psychomotor function and the EEG.
AB  - The effects of a single oral dose of alprazolam (1 mg), quazepam (15 mg) and
      diazepam (10 mg) on the peak saccadic velocity (PSV) of saccadic eye movements
      (SEM), the Sternberg memory scanning and choice reaction time (SMS-CRT), critical
      flicker fusion frequency (CFFF), spectral analysis of the EEG and a mood scale
      were assessed in 9 healthy volunteers in a double-blind, placebo-controlled cross
      over study. Alprazolam revealed greater sedative effects than diazepam in the
      above-mentioned tests. Quazepam had the least sedative effect of the 3 drugs
      tested, showed a time lag at the onset of its effects and a more prolonged effect
      on psychomotor impairment than reported previously.

PMID- 1982883
TI  - Evidence against extended DR3-related haplotypes in Graves' disease.
AB  - Three HLA-DR3-linked polymorphisms of the DPA, DPB and DRB genes, previously
      associated with myasthenia gravis or coeliac disease, have been examined in
      Caucasian patients with Graves' disease. The patients did not differ from healthy
      DR3 subjects, indicating an absence of any association of Graves' disease with
      specific DR3 subtypes.

PMID- 1982882
TI  - Quantitative and ultrastructural alterations in the lamina propria and Sertoli
      cells in human cryptorchid testes.
AB  - A quantitative and ultrastructural study was performed on biopsies of human
      cryptorchid testes to investigate lesions in the lamina propria and Sertoli
      cells. Prepubertal cryptorchid testes (1-9 years of age) were classified into
      four groups: Type 1, testes with minimal lesions; Type II, testes with a moderate
      decrease in tubule diameter and spermatogonal number; Type III, testes with
      Sertoli cell hypoplasia and a marked reduction in tubule diameter and
      spermatogonal number; and Type IV, testes with Sertoli cell hyperplasia and a
      variable reduction in spermatogonal number. An increase in thickness of the
      lamina propria was found in Type II and III testes from 5 years of age onwards.
      These testes also showed a decrease in both the average number of peritubular
      cells per cross-sectioned tubule and in the average nuclear volume of these
      cells. Most of the postpubertal cryptorchid testes from 13- to 18-year-old youths
      presented a prepubertal pattern suggestive of delayed testicular maturation.
      Postpubertal testes from 19- to 27-year-old men were classified into three types:
      Type A testes showed complete spermatogenesis, mature Sertoli cells and no
      lesions in the lamina propria; Type B testes showed isolated spermatogonia,
      mature Sertoli cells, and a marked thickening of the lamina propria; and Type C
      testes showed isolated spermatogonia, hyperplasia of immature Sertoli cells, and
      a slightly thickened lamina propria. Maturation of the lamina propria was always
      associated with maturation of the Sertoli cells. Thickening of the lamina propria
      was associated with peritubular cell alterations consisting of decreases in the
      nuclear volume (average and total per testis) of peritubular cells and increases
      in the number of these cells per cross-sectioned tubule. The three types of adult
      cryptorchid testes appear to be the postpubertal transformation of Type 1 testes
      (Type A), Type II and Type III testes (Type B), and Type IV testes (Type C).

PMID- 1982884
TI  - Therapeutic drugs and drugs of abuse in the era of the drug-free workplace.
      Proceedings of a symposium. Haight Ashbury Free Medical Clinics, May 1990, San
      Francisco.

PMID- 1982885
TI  - The use of benzodiazepines in the workplace.
AB  - Benzodiazepines differ from many of the other abused substances in that there are
      legitimate medical indications for their use. Any prescription for
      benzodiazepines must be preceded by a careful risk-benefit analysis that
      considers the specifics of an individual's particular life situation, personality
      style, and psychiatric diagnosis. The risk of benzodiazepine abuse by chemically
      dependent individuals and the problems of cognitive and/or psychomotor impairment
      and dependence for all individuals have to be balanced against the therapeutic
      benefits of these drugs for patients who experience disabling anxiety disorders
      or anxiety that accompanies chronic medical illness. Problems of dependence can
      be minimized by utilizing a variety of pharmacologic and psychotherapeutic
      strategies to ameliorate withdrawal symptoms that might accompany the
      discontinuation of long-term benzodiazepine treatment.

PMID- 1982886
TI  - Relationship between serum gamma-glutamyl transpeptidase activity and blood
      pressure in middle-aged male and female non-drinkers.
AB  - Serum gamma-glutamyl transpeptidase (gamma-GTP) activity is a biological
      parameter for alcohol consumption. In our previous study, however, serum gamma
      GTP levels seemed to correlate with blood pressure levels in both middle-aged
      male non-drinkers and drinkers. Therefore, the associations between gamma-GTP and
      BP were analysed more minutely in 385 male and 1126 female non-drinkers. The
      means of systolic (SBP) and diastolic (DBP) pressure in the males were
      significantly higher than those in the females, despite similar age and body mass
      index (BMI). The sex difference of BP disappeared after adjustment for serum
      gamma-GTP levels. The correlations between gamma-GTP and BP and the contributions
      of three variables, age, BMI, and gamma-GTP, to BP levels found in the non
      drinkers in the present study were similar to those observed in the previous
      study on males including drinkers. These results suggest that common or possibly
      similar mechanisms which relate to the elevation of serum gamma-GTP activity are
      involved in the production of high BP both in non-drinking obese persons and in
      drinkers.

PMID- 1982887
TI  - erbB-2 gene expression in colorectal cancer.
AB  - The expression of the erbB-2 gene product was studied immunohistochemically on 38
      normal colonic mucosae, 14 adenomas and 44 colon cancers, with the use of two
      anti-erbB-2 antibodies, a rabbit polyclonal antibody specific for the
      intracellular domain and a mouse monoclonal antibody specific for the
      extracellular domain. Normal mucosae and adenomas were not stained. Five cases
      (11%) of colon cancer were positive with the polyclonal anti-erbB-2 antibody,
      while only one case was positive with the monoclonal antibody. Most of the
      positive cases were in Dukes C stage. The rare overexpression of the erbB-2
      protein in colon cancer seems to indicate a minor role for the gene in colorectal
      tumorigenesis.

PMID- 1982889
TI  - Symposium on structure, function, and product of genes. The Second Kitasato
      Research Conference. July 22, 1989, Kitasato.

PMID- 1982888
TI  - Tyrosine hydroxylase activity in discrete brain regions of depression model rats.
AB  - Tyrosine hydroxylase (TH) activity was measured in discrete brain regions of rats
      during short-term forced running stress (FRS). TH activity was also determined in
      a depression-like state and in a recovered state after a long-term FRS. Under the
      short-term FRS, the TH activity showed a significant increase in the locus
      ceruleus, certain limbic regions and tuberoinfundibular system. In the depression
      like state, however, there was a significant decrease in the locus ceruleus and
      certain limbic regions, but a significant increase was seen in the median
      eminence. The TH activity in recovered rats showed no difference from the level
      in the controls. These findings demonstrate an adaptive increase in the TH
      activity in relation to stress, and may also indicate a failure of adaptation in
      the depression-like state.

PMID- 1982890
TI  - Association of HLA-DR antigens with disease severity in Japanese patients with
      rheumatoid arthritis.
AB  - Twenty eight Japanese patients with rheumatoid arthritis (RA) were tested for HLA
      DR antigens to investigate genetic influence on disease severity and prognosis.
      The severity of RA was assessed by clinical, laboratory and radiological indexes.
      HLA-A, B, C and DR typing was performed using sera described at the 3rd Asia and
      Oceania Histocompatibility Workshop. HLA-DR4.1 was significantly higher in RA
      patients (50%) compared with controls (27.6%). HLA-DRw53 was also higher in RA
      patients, although DRw52 was lower in those than controls. When the relationship
      between HLA-DR antigens and the clinical severity of RA was investigated, the
      patients with HLA-DR4 had a severer disease than DR4 negative patients. In
      contrast, HLA-DR2 positive patients had significantly better functional scores
      than DR 2 negative patients. We next investigated specific genes likely to be
      directly involved in the pathogenesis of RA. Although the new restriction
      fragment length polymorphisms (RFLPs) were found in DR2 positive patients, no
      association was found between the RFLPs and the clinical severity of RA.
      Furthermore there were no differences in the frequencies of the RFLPs in HLA-DR4
      positive patients compared with DR4 negative patients. It may be concluded that
      the severity of RA appears to be influenced by several different genes or
      molecules rather than by a single gene or gene product linked to HLA-DR2 or DR4.

PMID- 1982891
TI  - Inflammatory bowel disease therapies for the 1990s: scientific basis and clinical
      experience. Report of a symposium. December 8, 1989, New York City.

PMID- 1982892
TI  - Aminosalicylates: old and new.

PMID- 1982893
TI  - Effects of D-2 agonists on the release of dopamine: localization of the mechanism
      of action.
AB  - Brain microdialysis was used to localize the mechanism of action of the effect
      induced by the D-2 agonists (-)-2-(N-propyl-N-2-thienylethylamino)-5
      hydroxytetralin [(-)-N-0437] and (+)-4-propyl-9-hydroxynaphtoxazine [(+)-PHNO],
      on the release of DA in the striatum. Both agonists induced a stronger decrease
      in the release of DA when administered systemically in comparison to local
      administration. This suggests that the action of D-2 agonists is not exclusively
      mediated by autoreceptors regulating the release of DA at the level of the nerve
      terminals. By co-infusing nomifensine (10 microM) the effect of intrastriatally
      administered D-2 agonists on the release of DA could be completely abolished. As
      both agonists were effective when administered systemically in normal rats and in
      rats with kainic acid lesions performed in the striatum during nomifensine
      infusion, the effects induced by D-2 agonists seem to be partly mediated by
      autoreceptors situated on cell bodies, regulating the impulse flow of the neuron.
      In addition, D-2 receptors located on postsynaptic structures participating in
      the striatonigral feedback loops were suggested to be involved. (-)-N-0437 and
      (+)-PHNO were less effective after systemic administration when kainic acid
      lesioned rats were used in comparison with normal rats. Thus, D-2 agonists
      interact in a complex way with D-2 receptors for displaying their effect on the
      release of DA: autoreceptors situated on nerve terminals and on cell bodies as
      well as D-2 receptors located on postsynaptic structures participating in the
      striatonigral neuronal loops may all be involved to a certain extent in the
      mechanism of action of D-2 agonists.

PMID- 1982894
TI  - Transdermal administration of the dopamine agonist N-0437 and seven ester
      prodrugs: comparison with oral administration in the 6-OHDA turning model.
AB  - The potent and selective D2-agonist N-0437 [2-(N-propyl-N-2-thienylethylamino)-5
      hydroxytetralin] undergoes considerable first-pass metabolism after oral
      administration due to glucuronidation of the phenolic group. In an attempt to
      improve its bioavailability, seven ester prodrugs of N-0437 were synthesized,
      i.e. the acetyl-, propionyl-, isobutyryl-, pivaloyl-, 2-amino-phenyl-, 2-methoxy
      phenyl- and 2,4-dimethylphenyl-analogues. In vivo activities were assessed by
      measuring contralateral turning after transdermal administration of N-0437 and
      its prodrugs to rats with unilateral 6-OHDA lesions of the nigrostriatal pathway.
      From time-effect curves the area under the curve for separate time intervals was
      taken as a measure of dopaminergic activity during that interval. It was found
      that slowly hydrolyzing prodrugs, which are known to show an improved duration of
      action after oral administration, are devoid of activity after transdermal
      application. The acetyl-, the propionyl- and the isobutyryl analogues, which are
      prodrugs with a relatively high hydrolysis rate, were found to have interesting
      and promising profiles following transdermal application.

PMID- 1982895
TI  - A human glioma cell line retaining expression of GFAP and gangliosides,
      recognized by A2B5 and LB1 antibodies, after prolonged passage.
AB  - A malignant astrocytoma was cultured from a tissue biopsy taken at surgical
      resection, and serially passaged 65 times over a period of 4 years. Early culture
      cells showed a variety of morphological types, but were all positively labelled
      with a polyclonal antibody directed against glial fibrillary acidic protein
      (GFAP). As the number of passages increased small, GFAP-positive cells became the
      predominant cell type. Flow cytometry demonstrated changes in GFAP expression
      between early and late passages; early passages showing greater fluorescence
      intensity than those at later passages. All cells, however, remained positive for
      GFAP. In addition, this line (IPSB-18) was both vimentin and glutamine synthetase
      positive and no change in the expression of these two proteins was detectable on
      continued sequential passaging. Fibronectin was not detectable at any stage. As
      the number of passages increased, the population doubling time was shortened from
      72 h at passage 5, to 28 h at passage 30. This line is unusual in its retention
      of GFAP expression through 65 sequential passages; the majority of astrocytoma
      lines lose this capacity after a few passages in vitro. The monoclonal antibody,
      A2B5, which recognizes surface gangliosides, has been previously shown to
      identify sub-set type 2 astrocytes in normal neural tissue in vitro. The
      expression of A2B5 gangliosides by 5-20% of GFAP-positive IPSB-18 cells, and
      their co-expression with the ganglioside GD3 identified by the LB1 monoclonal
      antibody, shows that cells with a similar phenotype to the type 1 and type 2
      astrocytes of optic nerve are present in cultured gliomas, even after long term
      sequential passaging.

PMID- 1982897
TI  - Posthumous diagnosis of X-linked retinoschisis using DNA analysis.
AB  - X-linked juvenile retinoschisis usually results in a rather serious visual
      handicap in affected males. However, occasionally patients can present with very
      subtle clinical signs without subjective complaints. For this reason, the family
      history can be misleading and caution is necessary when analysing the pedigree
      and giving genetic advice. In this report a family with X-linked retinoschisis is
      described in which segregation analysis with DNA probes strongly suggests that
      the deceased grandfather, who was said to have had good vision, had been affected
      by juvenile retinoschisis.

PMID- 1982896
TI  - In quest of the tyrosinase-positive oculocutaneous albinism gene.
AB  - The gene which causes tyrosinase-positive oculocutaneous albinism (ty-pos OCA) is
      not known. Forty-seven Bantu-speaking Negroid families with ty-pos OCA were
      studied in an attempt to find linkage to the gene. Fifteen 'classical' and seven
      DNA polymorphisms were used in the search for linkage. Close linkage was excluded
      for the Rh, Gc and beta-globin loci. There is no suggestion of linkage to MNS,
      ABO, PGM1, 6PGD, ACP1, GPX1, GLO1, GPT1, PEP A, Tf, alpha 1-AT, Hp, DQA, DXA and
      three arbitrary restriction fragment length polymorphisms (RFLPs). There is a
      slightly positive lod score for pAW101 (D14S1) (0.591 for theta = 0.2). An
      'interesting' lod score was obtained with Bf and a haplotype generated by the
      markers DQA and DXA (1.575 for theta = 0.1 and 0.979 for theta = 0.2,
      respectively). Further testing of markers on chromosome 6p are indicated.
      Although ty-pos OCA in Southern Africa is likely to be a homogeneous disorder,
      genetic heterogeneity cannot be excluded as differences due to the
      presence/absence of ephelides within families have been observed. To date 57% of
      the genome has been excluded from linkage with ty-pos OCA.

PMID- 1982898
TI  - Plasma concentrations and haemodynamic effects of d-sotalol after beta-blockade
      in dogs.
AB  - This study was designed to investigate the haemodynamic effects of d-sotalol at
      plasma concentrations producing class III antiarrhythmic effects. d-Sotalol 1, 4
      and 10 mg/kg intravenously was given after beta-blockade (propranolol 0.25 mg/kg
      intravenously) to seven pentobarbital anaesthetized dogs. Left ventricular (LV)
      systolic and end-diastolic pressures, LV dP/dtmax, mean aortic pressure, stroke
      volume, cardiac output and total peripheral resistance were not significantly
      changed by d-sotalol. There was a linear correlation between the dose of d
      sotalol infused and the plasma concentration of d-sotalol obtained. Heart rate
      decreased and QT-time increased with increasing plasma concentrations of d
      sotalol, whereas the QRS-width did not change. There was a linear correlation
      between the decrease in heart rate and the increase in QT-time, and between the
      plasma concentration of d-sotalol and increase in QT-time. In conclusion, the
      study indicates that after beta-blockade, d-sotalol has no cardiodepressive
      effects at concentrations that prolong repolarization.

PMID- 1982900
TI  - Evidence that mutacin II production is not mediated by a 5.6-kb plasmid in
      Streptococcus mutans.
AB  - Here we present evidence that the cryptic 5.6-kb plasmid found in certain strains
      of Streptococcus mutans is not involved in mutacin production. This evidence
      comes from demonstrating similarities between a plasmid-less strain T8 and a
      group II plasmid strain UA96. Both produce what appears to be an identical
      mutacin based on spectrum of activity and physiological properties. Also, T8 and
      UA96 are members of the same immunity group (group II). Genotypically, both
      strains appear similar except for plasmid content based on DNA fingerprinting
      profiles. T8 and UA96 exhibit identical hybridization patterns following
      transformation of T8 with a mutacin-negative (bac-1::Tn916) sequence from a Tn916
      insertionally inactivated mutant of UA96. This transformation also resulted in
      the mutacin-negative phenotype in T8 transformants, showing recombination between
      a mutacin-associated gene in UA96 and its apparent homologous sequence in T8.
      Moreover, when a plasmid containing a putative repeat element from UA96 (pPC264)
      was used as a probe, it hybridized to the same five EcoRI fragments in both T8
      and UA96. Collectively, these data, coupled with data from other sources,
      indicate that the plasmid resident in mutacin II strains is not involved in
      mutacin production.

PMID- 1982899
TI  - Direct comparison between the ulcer-healing effects of two H(+)-K(+)-ATPase
      inhibitors, one M1-selective antimuscarinic and one H2 receptor antagonist in the
      rat.
AB  - A direct comparison of the ulcer-healing effects of two H(+)-K(+)-ATPase
      inhibitors (pantoprazole and omeprazole), one M1 antimuscarinic (telenzepine) and
      one H2 receptor antagonist (cimetidine) was performed in the rat. Gastric and
      duodenal ulcers were induced by local application of acetic acid and thereafter
      treated over 10 days by the test drugs. Overall and on a molar basis, ulcer
      healing was comparably accelerated by pantoprazole, omeprazole and telenzepine
      and less so by cimetidine. The same rank order was found with respect to the
      inhibition of gastric acid secretion in the modified Shay rat.

PMID- 1982901
TI  - Effects of neuroleptics on electrodermal activity in schizophrenic patients: a
      review.
AB  - The effects of neuroleptics on electrodermal activity (EDA) in schizophrenic
      patients are addressed in a review of research conducted since the publication of
      an earlier review by Tecce and Cole in 1972. It is concluded that neuroleptics
      reduce skin conductance level but that effects on other electrodermal parameters
      are less robust and may be confounded by methodological issues. A discussion of
      these issues is presented and directions for future research are proposed.

PMID- 1982902
TI  - Neuroleptic-induced vacuous chewing movements as an animal model of tardive
      dyskinesia: a study in three rat strains.
AB  - Vacuous chewing movements (VCMs) in three different rat strains developed at
      considerably different rates after 19 weeks of continual haloperidol treatment at
      an average daily dose of 1.5 mg/kg. Sprague Dawley (SD) rats displayed relatively
      high rates of VCMs with low variability, compared to Wistar (W) and Long Evan
      (LE) rats. Atropine decreased but did not abolish VCMs in two of the three
      strains (LE greater than SD). After haloperidol withdrawal, VCMs remitted
      gradually in all strains, but least rapidly in the SD rats. In a separate group
      of SD rats. VCMs were rated weekly from the start of haloperidol treatment and
      showed considerable interindividual variability. Even after 24 weeks of
      continuous haloperidol, 12 out of 32 treated rats showed no VCMs at all, while 13
      out of 32 had intense movements, analogous to the clinical situation in which
      only some patients treated with neuroleptics develop tardive dyskinesia. These
      results indicate that there are individual and strain differences in the
      development of VCMs, and suggest that there may also be genetically determined
      differences in the development of tardive dyskinesia.

PMID- 1982903
TI  - Footshock-induced freezing behavior in rats as a model for assessing anxiolytics.
AB  - A number of chemically distinct anxiolytics were examined for effects on
      defensive behavior (foot-shock-induced freezing) in rats. Central nervous system
      acting drugs which are not anxiolytics were also studied. Animals were injected
      with a drug or vehicle (IP) prior to being placed in a chamber with a grid floor
      through which two footshocks were delivered. Behavior was observed during the pre
      shock period (2 min) and for 4 min after the second footshock. The effects of the
      following drugs on the duration of footshock-induced freezing were studied:
      diazepam (DZP); 2-amino-4,5-(1,2-cyclohexyl)-7 phosphonoheptonic acid (NPC
      12626); 3-((+/-)-2-carboxypiperazine-4-yl)-propyl-l-phosphonic acid (CPP); [(+)-5
      methyl-10-11,dihydroxy-5H-dibenzo(a,d)cyclohepten-5,10- imine (MK-801); buspirone
      hydrochloride (BUS); DL-amphetamine sulfate (AMP); haloperidol (HAL); ethyl-beta
      carboline-3 carboxylate (beta-CCE). Compounds which reduced the duration of
      footshock-induced freezing included DZP, BUS, and the competitive NMDA
      antagonists NPC 12626 and CPP. The non-competitive NMDA antagonist, MK-801, had
      no effect on the response. The highest dose of amphetamine tested also reduced
      footshock-induced freezing. However, amphetamine-treated animals did not locomote
      or rear after footshock, suggesting fear of the environment. Animals injected
      with DZP, NPC 12626, CPP or buspirone spent at least 1.4 of the 4 post shock
      minutes locomoting. Haloperidol had no effect on freezing at the doses tested.
      beta-CCE tended to increase the duration of footshock-induced freezing.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1982904
TI  - Effect of NMDA- and strychnine-insensitive glycine site antagonists on NMDA
      mediated convulsions and learning.
AB  - Intracerebroventricular (ICV) injection of N-methyl-D-aspartate (NMDA) was shown
      to induce generalized seizures in mice. The competitive NMDA antagonists DL-2
      amino-5-phosphonovaleroate (DL-AP7) and 3-(2-carboxypiperazin-4-yl)propyl-1
      phosphonate (CPP), the NMDA "channel blocker" antagonist (+)-5-methyl-10,11
      dihydro 5H-dibenzo-[a,d] cycloheptan-5,10-imine maleate (MK-801) and the
      strychnine-insensitive glycine antagonists kynurenic acid (KYNA) and 7-chloro
      kynurenic acid (7-Cl-KYNA), when co-administered (ICV) with NMDA, antagonized
      NMDA-induced generalized seizures. Administration (ICV) of DL-AP7, CPP and MK-801
      resulted in impared learning performance in a passive avoidance task in mice,
      with ED50 close to the anticonvulsant dose. The glycine antagonists KYNA and 7-Cl
      KYNA at high doses significantly failed to affect performance in the same model
      of learning. The results indicate that compounds acting at the strychnine
      insensitive glycine site may have a larger "therapeutic window" as
      anticonvulsants than antagonists of the NMDA receptor and channel.

PMID- 1982906
TI  - Anatomical basis of the anterolateral thigh flap.

PMID- 1982905
TI  - [Intensive chemotherapy with 1-3 drugs and support with autologous myelopoietic
      cells extracted from the peripheral blood: the preliminary results].
AB  - Fourteen patients with different solid tumors have been treated with high-dose
      combination chemotherapy followed by autologous PBSC support. A total of 15
      procedures have been done. 4,5-7 x 10(10) mononuclear cells were obtained through
      1-4 leukapheresis using a CS-3.000 continuous flow blood cell separator. Cells
      were maintained in standard culture conditions for 3-5 days prior to infusion.
      Chemotherapy consisted in the administration of 1-3 agents: CPA 80 mg/kg; VP-16,
      800 mg/m2; BCNU 700-800 mg/m2, CBDCA 1.000 mg/m2. APBSC were infused 48 hours
      after the last chemotherapy was given. Patients were maintained in single-bed
      rooms with standard prophylactic antibiotics, including gentamycin, piperacillin,
      vancomycin and amphotericin B during the period of aplasia. Currently 5
      procedures are available for response and all patients are evaluable for
      toxicity. Responses have been: 2 complete responses and 3 partial response. All
      patients entered in aplasia, with 12 infections (73%), 8 bleeding (53%), 4
      diarrhea (27%), 2 stomatitis (13%) and 3 renal failure (16%). CONCLUSIONS: 1.
      Bone marrow recovery after high dose chemotherapy can be shortened with APBSC
      support. 2. APBSC can be safely maintained using standard culture techniques,
      thus avoiding the freezing procedure.

PMID- 1982907
TI  - Potentiation of ethyl methanesulfonate-induced germ cell mutagenesis and
      depression of glutathione in male reproductive tissues by 1,2-dibromoethane.
AB  - EDB significantly depressed GSH in caput and cauda epididymis, but not in testis,
      2 hours following injection. This depression was dose-related. EDB enhanced EMS
      induced dominant lethal mutations at mating weeks 2 and 3 (of 6). At mating week
      2 the fetal death rate was increased two-fold, while at week 3, the fetal death
      rate had increased to nearly three-fold greater than the EMS-only controls.
      Enhancement of fetal death rate was confined to postimplantation loss. As with
      EMS alone, the EDB potentiation of EMS-induced mutations was limited to
      postmeiotic stages of spermatogenesis. EDB also enhanced alkylation of rat
      spermatozoa by labeled EMS. Depression of GSH in reproductive tissues is
      correlated with a potentiation of dominant lethal mutations, as well as an
      increase in the binding of EMS to sperm heads.

PMID- 1982908
TI  - Sensitivity of cultured lymphocytes from patients with nevoid basal cell
      carcinoma syndrome to ultraviolet light and phytohemagglutinin stimulation.
AB  - DNA repair and replication after in vitro UV irradiation were determined in
      cultured peripheral blood lymphocytes from 6 patients with nevoid basal cell
      carcinoma syndrome (NBCCS) and from a group of control donors. DNA repair
      synthesis (UDS) was measured in unstimulated lymphocytes by incubation with 3H
      TdR in the presence of hydroxyurea for 3 and 6 h after UV irradiation (6-48
      J/m2). DNA replication was measured in PHA-stimulated lymphocytes, UV-irradiated
      or mock-irradiated, by incubation with 3H-TdR for 24 h. The effect of the mitogen
      was followed during 5 days after stimulation by determining the incorporation of
      3H-TdR, the increase of cell number, and the mitotic index. NBCCS and control
      lymphocytes showed equal sensitivity to UV light in terms of UDS and reduced
      response to PHA. On the contrary, the mitotic index and the number of cells in
      stimulated cultures were significantly lower in the affected subjects. These data
      suggest an altered progression along the cell cycle, which could be
      characteristic of stimulated NBCCS lymphocytes.

PMID- 1982909
TI  - Evaluation of the genotoxicity of gentian violet in bacterial and mammalian cell
      systems.
AB  - Previous studies indicate that gentian violet (GV), a triphenylmethane dye used
      in agriculture and human medicine, is a clastogen in vitro and a carcinogen in
      chronically exposed mice and rats. Data on its genotoxic activity, however, have
      been incomplete and partly contradictory. Mutagenesis and DNA damage experiments
      were conducted to re-evaluate the genotoxic potential of GV in both bacterial and
      mammalian cell systems. GV was mutagenic in Salmonella typhimurium tester strains
      TA97 and TA104, but there was little mutagenic activity detected in strains TA98
      and TA100. A rat liver homogenate fraction (S9) tended to increase mutagenicity.
      The major microsomal metabolites of GV, pentamethylpararosaniline and N,N,N',N'
      tetramethylpararosaniline were less mutagenic in TA97 and TA104, while N,N,N',N"
      tetramethylpararosaniline was a weak mutagen in Salmonella. GV was not mutagenic
      in Chinese hamster ovary (CHO) cell strain CHO-K1-BH4, and was a questionable
      mutagen in CHO-AS52 cells. While GV produced DNA damage as measured by
      sedimentation of nucleotids derived from B6C3F1 mouse lymphocytes treated in
      vitro, no damage was found in lymphocytes isolated from mice dosed with GV. GV
      was also a weak producer of gene amplification in an SV40-transformed Chinese
      hamster cell line. The results indicate that GV is a point mutagen in bacteria;
      however, since similar exposure conditions produced weak mutagenic activity in
      mammalian cells, GV may be carcinogenic by virtue of its clastogenic activity.

PMID- 1982910
TI  - Analysis of the mechanism of isoniazid-induced developmental toxicity with frog
      embryo teratogenesis assay: Xenopus (FETAX).
AB  - The developmental toxicity of isoniazid (INH) and the metabolites acetylhydrazide
      (AH) and isonicotinic acid (INA) were examined with the frog embryo teratogenesis
      assay-Xenopus (FETAX). Late Xenopus laevis blastulae were exposed to INH, AH, and
      INA for 96 h in two separate static-renewal tests with and without the presence
      of three differently induced metabolic activation systems (MAS). The MAS
      consisted of uninduced, Aroclor 1254-induced, and INH-induced rat liver
      microsomes. Addition of the INH-induced MAS decreased the 96 h LC50 of INH and AH
      approximately 1.6-fold and 7.9-fold, respectively. The 96 h EC50 (malformation)
      of INH was virtually unaffected; however, the INH-MAS decreased the teratogenic
      index (TI) [96 h LC50/96 h EC50 (malformation)] nearly 1.8-fold. The 96 h EC50
      (malformation) of AH increased approximately 2.0-fold, decreasing the teratogenic
      index value 15.8-fold. INA yielded a teratogenic index value of 2.5. Neither the
      uninduced MAS nor the Aroclor 1254-induced MAS had an effect on any of the
      compounds tested and none of the MAS affected the developmental toxicity of INA.
      Results from this study suggest that mixed functional oxidase metabolism may
      alter the developmental toxicity of INH in vitro by producing a more
      embryolethal, but less teratogenic metabolite(s) than INH or AH themselves.
      Results are indicative of the utility and versatility of FETAX in evaluating
      toxicological mechanisms of teratogenesis in vitro.

PMID- 1982911
TI  - Interaction of drugs with extranuclear genetic elements and its consequences.
AB  - Bacterial ancestry of mitochondria and plastids is now generally accepted. Both
      organelles contain their own DNA and transcription-translation apparatus of a
      prokaryotic type. Due to this fact these systems carry bacteria-like properties.
      Thus organellar DNA and ribosomes are essentially different from nuclear DNA and
      cytoplasmic ribosomes in physical as well as in functional respects. Due to the
      bacterial character of both types of organelles they are susceptible to various
      antibacterial chemicals. Inhibitors of bacterial protein synthesis inhibit
      mitochondrial (plastidial) biogenesis. Therefore the cellular content of
      mitochondria (plastids)-made proteins decreases during cytoplasmic turnover or
      cell division in the presence of these drugs. Such drug activity consequently
      leads to a reduced capacity for oxidative phosphorylation or photosynthesis.
      Organellar genomes are less stable and more sensitive to mutagenesis as compared
      to nuclear genome. It means also that genotoxic agents induce various disorders
      of mitochondrial (plastidial) functions. Impairments in the respiratory chain are
      associated with structural as well as functional abnormalities of mitochondria.
      These are clinically expressed mostly in tissues with a high demand for ATP:
      brain, heart, skeletal muscle, and retina. On the other hand, some antibacterial
      inhibitors of mitochondrial biogenesis (e.g., tetracyclines) inhibit selectively
      tumor cell proliferation. Therefore they may be considered for use in anticancer
      therapy. The article summarizes the response of mitochondria and plastids in
      various organisms to drugs and environmental xenobiotics. Various model organisms
      suitable for detection of xenobiotic effect on mitochondria (plastids) are
      presented as well as the possible consequences of such interaction.

PMID- 1982912
TI  - [The role of beta-blockers in the preventive treatment of rupture of esophageal
      varices].
AB  - beta-blockers, mainly propranolol, have dramatically modified the treatment of
      portal hypertension. It has been demonstrated that it was possible to decrease
      portal pressure over a long period and to modify the natural history of
      gastrointestinal bleeding in cirrhosis. The prevention of first bleeding, or
      primary prophylaxis, should be distinguished from prevention of rebleeding, or
      secondary prevention, as these two situations pertain to different events.
      Concerning primary prophylaxis, at least five randomized controlled trials,
      (RCT), comparing beta-blockers and placebo, have been published. All the results
      are homogenous and their meta-analysis suggests that the incidence of first
      bleeding is significantly decreased but not that of death rate. Results of
      studies comparing propranolol and sclerotherapy are also available but we know
      that the results of more than 15 RCT testing sclerotherapy are debated. In
      secondary prevention, there are more than 10 RCT comparing beta-blockers versus
      placebo. Results of these RCT are heterogeneous. Meta-analysis suggests that the
      incidence of rebleeding is significantly decreased but not that of death rate.
      The results of 5 RCT comparing propranolol versus sclerotherapy are available.
      Whatever the trial, there was no significant differences between these two
      treatments. However, meta-analysis suggests that the bleeding incidence is
      decreased by sclerotherapy but this does not reach statistical significance.
      Finally, there are RCT with combined treatments: it seems that sclerotherapy plus
      propranolol is superior to sclerotherapy alone; however this result should be
      confirmed. In conclusion beta-blockers seem to bring about real changes in the
      prevention of digestive bleeding in cirrhosis. Their contribution is particularly
      appreciable in primary prevention of cirrhotic patients with large oesophageal
      varices.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1982913
TI  - Somatostatin in the treatment of bleeding oesophageal varices.
AB  - Somatostatin has been evaluated in the treatment of patients with bleeding
      varices for the past 10 years. Six controlled trials are published and a large
      placebo controlled trial has been reported in abstract form. From these trials it
      appears that somatostatin is at least as effective as vasopressin or H2
      antagonists and is more effective than placebo in the control of variaceal
      haemorrhage. It is also remarkably free of side effects in clinical practice.

PMID- 1982915
TI  - Oxygen transport to tissue XII. Proceedings of the 17th annual meeting of the
      International Society on Oxygen Transport to Tissue. July 21-24,1989, Goettingen,
      Federal Republic of Germany.

PMID- 1982914
TI  - The current status of gastric prokinetic drugs.
AB  - Several current gastrokinetic drugs (metoclopramide, domperidone, cisapride) are
      analysed in this review. After comparing the pharmacokinetics, the
      gastrointestinal prokinetic mechanisms and the side effects of each drug, their
      therapeutic uses are reviewed. All drugs improve symptoms of patients with gastro
      oesophageal reflux disease, diabetic gastroparesis and idiopathic gastroparesis,
      but only cisapride seems capable to maintain a gastrokinetic effect under chronic
      administration. Erythromycin, which has a dramatic effect on hypomotility in
      diabetic gastroparesis, and opioid antagonists, may constitute new groups of
      efficient prokinetic drugs.

PMID- 1982916
TI  - Actions of a dopaminergic and beta 2-adrenergic agonist on O2 extraction by
      canine skeletal muscle.
AB  - We have shown that an unopposed stimulation of beta-vasodilator adrenoceptors can
      cause a decreased ability of skeletal muscle to extract O2 when O2 delivery was
      progressively lowered. The significance of this finding with respect to the
      application of dopexamine to cardiac failure or to any other condition that
      causes a decrease in peripheral O2 delivery, however, needs to be assessed when
      an appropriate increase in vasoconstrictor tone is allowed to occur.

PMID- 1982917
TI  - Stimulation of phospholipases A2 by transglutaminases.

PMID- 1982918
TI  - Synthesis and antinociceptive activity of 4-pyridyl and -dihydropyridyl analogues
      of meperidine and ketobemidone.
AB  - The synthesis and antinociceptive activity of 4-pyridylpiperdines (7 and 10) in
      which the phenyl group pf meperidine (1) or ketobemidone (3) is replaced by 2'-,
      3'- or 4'-pyridyl is described. All were active in a rat writhing test, and the
      results showed that the point of attachment of the pyridyl ring to the 4-position
      was an important determinant of the activity; the relative potency order was 3'
      pyridyl greater than 4'-pyridyl greater than 2'-pyridyl in each of the two
      series. The most potent compound (half the potency of meperidine) was 4
      ethoxycarbonyl-4-(3'-pyridyl)-l-methylpiperidine (7b). This compound, and the
      corresponding 4'-isomer (7c), were further elaborated to provide 1'-phenyl, 1',6'
      dihydropyridine (11), and 1'-phenyl, methyl or n-butyl. 1',2'-dihydropyridine
      (12) analogues containing an acyl function on the ring nitrogen. The most active
      compound in this series was 4-[4'-(1'-phenoxycarbonyl-2'-n-butyl-l',2'
      dihydropyridyl)]- 4- ethoxycarbonyl-l-methylpiperdine (12k). Though less potent
      than the parent pyridyl compound (7c), it induced 70% inhibition in the writhing
      test at a dose of 8 mg/kg sc. [The ED50 for meperidine was 0.6 mg/kg sc.]

PMID- 1982919
TI  - [Multiple receptor interactions in the electrically stimulated ductus deferens of
      the guinea-pig].
AB  - The evidence that ATP is released with noradrenaline as a cotransmitter from
      sympathetic nerve endings in the isolated guinea-pig vas deferens, had led to
      investigate the potential interactive effects of P2 and alpha 1 receptors,
      extending the observations to potentially synergistic interactions of histamine-,
      acetylcholine- and serotonin-receptors. Ineffective concentrations of histamine,
      carbachol and serotonin increase the neurogenic response to field stimulation;
      this effect is prevented by the specific antagonist. The responses to the
      exogenously applied ATP and noradrenaline are increased as well, suggesting that
      this synergistic interaction of carbachol is less specific. It can be envisaged
      that receptor complex is a multicomponent system with subunits specific for the
      primary neurotransmitter and accessory subunits which may interact to increase
      the responsiveness of the target cell to simultaneous afferent stimuli.

PMID- 1982920
TI  - Network of interactions among pair-rule genes regulating paired expression during
      primordial segmentation of Drosophila.
AB  - A model of the trans-regulation of the Drosophila pair-rule segmentation gene,
      paired (prd), has been derived from the observed alterations in the distribution
      of prd transcripts during early embryogenesis in single and double pair-rule
      mutants. Important aspects of the model include the following features and
      implications: (i) The regulation of prd is subject to a regulatory hierarchy
      among pair-rule genes. In particular, it shows that prd is at the bottom of this
      hierarchy, mediating the transition from pair-rule to segment-polarity genes. The
      transition of the early 'pair-rule' to the 'segment-polarity' pattern of prd
      expression is regulated by the secondary pair-rule genes opa and odd. The model
      predicts the distributions of pair-rule gene products regulating prd at late
      syncytial blastoderm, e.g., that of opa. (ii) The initial activation of prd is
      independent of pair-rule genes. (iii) The regulation of prd is combinatorial and
      hence probably cooperative. Combination of one pair-rule gene product with
      different pair-rule proteins may lead to opposite regulatory effects on prd.
      Furthermore, we discuss a two-step conversion of the initial analogue
      specification of position along the anteroposterior axis into a digital code
      specified by combinations of active segment-polarity and homeotic genes.

PMID- 1982921
TI  - The murine paired box gene, Pax7, is expressed specifically during the
      development of the nervous and muscular system.
AB  - Eight murine paired box-containing (Pax) genes have been isolated so far. The
      gene described here, Pax7, contains not only a paired box, but also an
      octapeptide and a paired-type homeobox. As shown by Northern and in situ
      analysis, Pax7 is expressed from day 8 to 17 p.c. during embryogenesis. At early
      stages Pax7 transcripts are present in a subset of cells throughout the entire
      brain, but later in development expression is limited to the mesencephalon. In
      the developing neural tube Pax7 is restricted to the dorsal ventricular zone
      along the entire antero-posterior axis, suggesting a role for Pax7 in the
      formation of certain parts of the CNS. Additionally Pax7 expression can be
      followed during myogenesis from the dermamyotome of the somites to the skeletal
      muscle tissues.

PMID- 1982922
TI  - Regulation of Kruppel expression in the anlage of the Malpighian tubules in the
      Drosophila embryo.
AB  - The expression of most Drosophila segmentation genes is not limited to the early
      blastoderm stage, when the segmental anlagen are determined. Rather, these genes
      are often expressed in a variety of organs and tissues at later stages of
      development. In contrast to the early expression, little is known about the
      regulatory interactions that govern the later expression patterns. Among other
      tissues, the central gap gene Kruppel is expressed and required in the anlage of
      the Malpighian tubules at the posterior terminus of the embryo. We have studied
      the interactions of Kruppel with other terminal genes. The gap genes tailless and
      huckebein, which repress Kruppel in the central segmentation domain, activate
      Kruppel expression in the posterior Malpighian tubule domain. The opposite effect
      on the posterior Kruppel expression is achieved by the interposition of another
      factor, the homeotic gene fork head, which is not involved in the control of the
      central domain. In addition, Kruppel activates different genes in the Malpighian
      tubules than in the central domain. Thus, both the regulation and the function of
      Kruppel in the Malpighian tubules differ strikingly from its role in
      segmentation.

PMID- 1982924
TI  - Degradation of N5-(2-hydroxyethyl)-L-glutamine and L-glutamic acid homopolymers
      and copolymers by papain.
AB  - The rate of degradation of poly[N5-(2-hydroxyethyl)-L-glutamine] (PHEG), poly(L
      glutamic acid) (PGA) and poly[HEG-co-GA] random copolymers by papain was measured
      in the pH range 4.0-7.5, employing the gel permeation chromatography method. The
      effect of the degree of ionization on the polymer conformation was measured by
      circular dichroism (c.d.). PHEG, which is uncharged, had a random coil
      conformation and an almost constant degradation rate within the whole pH
      interval. The ionization of PGA increased with increasing pH and was accompanied
      by conformational transition from helix to random coil. The hydrolysis of PGA by
      papain depended on pH with the optimum at about pH 5, indicating that both the
      high content of helix (at pH less than 5) and increasing charge density (at pH
      greater than 5), decreased the degradation rate. Contrary to PGA, pH profiles of
      the degradation rate of poly[HEG-co-GA] copolymers are monotonous and do not
      decrease at pH less than 5. In the copolymers the HEG residues act as a helix
      breaker and limit the formation of helical conformation. The role of structural
      features of a macromolecular substrate, i.e. the charge, helical conformation and
      the nature of amino acid residues, in the interaction between enzyme and polymer
      is discussed.

PMID- 1982923
TI  - Altering the regulatory targets of the Deformed protein in Drosophila embryos by
      substituting the Abdominal-B homeodomain.
AB  - The homeotic selector genes of Drosophila melanogaster encode transcriptional
      regulatory proteins that control the determination of different segmental fates.
      Binding of selector proteins to regulatory DNA sequences is mediated by an
      evolutionary conserved protein domain, the homeodomain. Although homeodomains
      encoded by the selector genes are very similar in their amino acid sequence and
      in vitro DNA-binding properties, here we provide additional evidence that the
      homeodomain is responsible for most of the regulatory specificity of the entire
      protein. A heat-shock promoter/selector gene was constructed that encodes a
      Deformed/Abdominal-B chimera in which the Abdominal-B homeodomain is substituted
      for that of Deformed. Expression of this chimeric protein throughout the embryo
      causes morphological transformation of anterior segments toward more posterior
      identities. A number of other homeotic selector genes, all normally repressed by
      Abdominal-B, are ectopically activated by the chimeric protein. These results
      support the hypothesis that the target specificity of similar homeodomain
      proteins is largely determined by the amino acid sequence of the homeodomain.

PMID- 1982925
TI  - Analysis of isoactin expression in cultured mouse cells by in situ hybridization.
AB  - The expression of cytoskeletal isoactin genes in NIH 3T3 and L cells was studied
      by in situ hybridization. Anti-sense RNA probes specific for beta- and gamma
      actin were prepared by in vitro transcription of the 3'-untranslated regions of
      each cDNA which diverge in an isoactin-specific manner. Both NIH 3T3 and L cells
      showed a higher expression of beta- and gamma-actin mRNAs in a growing state than
      in a stationary one. Among these changes, the suppression of gamma-actin mRNA in
      L cells was most prominent and that of beta-actin in 3T3 cells was least
      profound.

PMID- 1982926
TI  - Pre-clinical evaluation of anti-lacto-N-fucopentaose III (CD15) monoclonal
      antibodies for ex vivo bone marrow purging in acute myeloid leukemia.
AB  - In order to eliminate residual leukemic cells from the marrow of patients with
      acute myeloid leukemia (AML) prior to autologous bone marrow transplantation, the
      optimal conditions of utilization of three CD15 murine monoclonal antibodies
      (MoAb) were investigated. The VIM-D5 MoAb was used with rabbit complement (C'),
      whereas the 8.27 and SMY15A MoAbs were used in the presence of human C'. These
      antibodies were also tested after fixation on magnetic beads. In a culture assay
      in semi-solid medium with a mixture of normal marrow and 1% HL60 cells, a lysis
      of clonogenic cells greater than 99% was achieved with the three antibodies and
      two rounds of complement, or with antibody-coated magnetic beads. Cultures of
      leukemic clonogenic cells (CFU-L) were performed in 47 cases. An inhibition equal
      to or greater than 90% was achieved in seven cases with VIM-D5, 16 cases with
      8.27 and 11 cases with SMY15A and C'. The correlation with cytotoxicity of fresh
      cells was low. Twenty cases were purged with antibody-coated beads. An inhibition
      equal to or greater than 90% was observed in 10 cases with VIM-D5, 11 cases with
      8.27 and 12 cases with SMY15A. The mean recovery of normal CFU-GM was higher than
      70% and that of BFU-E higher than 95% with any method of treatment. It is
      concluded that efficient marrow purging of clonogenic AML cells can be achieved
      in some cases without toxicity for normal progenitors. The addition of other
      MoAbs seems necessary to obtain a significant purge in a majority of cases.

PMID- 1982927
TI  - A phase I-II study of high-dose cyclophosphamide, thiotepa and escalating doses
      of mitoxantrone with autologous stem cell rescue in patients with refractory
      malignancies.
AB  - Twenty-five patients with refractory solid tumors were treated with high-dose
      cyclophosphamide, thiotepa and mitoxantrone followed by autologous stem cell
      rescue in a phase I dose escalation study. The dose-limiting toxic effect was
      mucositis at 60 mg/m2 of mitoxantrone in combination with cyclophosphamide and
      thiotepa. The early death rate due to toxic effects was 24%; all deaths were
      attributed to infections. Hematopoietic recovery was quite prolonged with median
      times to granulocyte (greater than 500 x 10(6)/l) and platelet (greater than 50 x
      10(9)/l) recovery at 58 and 148 days, respectively. The overall response rate was
      56%. The median time to progression was 14 weeks. Thus, this regimen has activity
      against refractory malignancies although early and prohibitive toxicity occurs
      when mitoxantrone is escalated in this setting.

PMID- 1982928
TI  - Oro-facial and dental injuries in club rugby union players.
AB  - Oro-facial and dental injuries are of particular importance as dental tissues
      have a low potential for recovery when damaged and such injuries can give rise to
      functional, aesthetic and psychological disfigurement. Also their repair can be
      costly, distressing and time consuming. This study sought to clarify the nature
      and severity of oro-facial injuries amongst rugby players in a first division
      club in Scotland. A secondary aim of the study was to examine the influence of
      position and standard of play on injury rates. The results show that oro-facial
      injuries are common amongst rugby players, and that players in the first fifteen
      were at the greatest risk. Although injuries may still occur when mouthguards are
      used, their severity will be reduced by use of such protective devices.

PMID- 1982929
TI  - Endodontic management of trauma to permanent teeth.
AB  - Oral trauma is a common event. It has been estimated that up to 20% of the United
      States population has sustained injuries to the teeth. In a perspective study,
      Andreasen reported that one of every two Danish children had sustained an oral
      injury by age 14. This article will discuss the different types of injuries that
      can happen to permanent teeth, endodontic management of these injuries, and
      possible complications. Exarticulations (totally avulsed teeth) will not be
      thoroughly discussed.

PMID- 1982930
TI  - Protective effects of nipradilol, isosorbide dinitrate, and bunazosin on coronary
      artery constriction induced by intracoronary injection of acetylcholine in pigs.
AB  - STUDY OBJECTIVE: Protective effects of nipradilol, a newly synthesised
      vasodilating beta adrenoceptor antagonist, isosorbide dinitrate, and bunazosin on
      coronary artery constriction induced by intracoronary injection of acetylcholine
      were determined by coronary arteriography and compared in vivo in pigs. DESIGN:
      Acetylcholine (12.5, 25, 50, 100 and 200 micrograms) was given into the right
      coronary artery under left ventricular pacing to maintain constant systemic
      haemodynamics. Percentage narrowing of the major epicardial coronary artery was
      used as an indicator of constriction of the large coronary arteries, and the time
      required for the contrast medium to reach the posterior descending coronary
      artery from the ostium of the right coronary artery (blood flow delay) was used
      as an indicator of constriction of the small coronary arteries. SUBJECTS: 15 farm
      pigs weighing 80 to 90 kg were used. MEASUREMENTS AND MAIN RESULTS: A marked
      blood flow delay of over 7.0 s (control: less than or equal to 1.8 s) with less
      than 34% narrowing of the epicardial major coronary artery was observed in 13 of
      15 pigs with 12.5-50 micrograms of acetylcholine, and in the other two pigs with
      100 micrograms of acetylcholine. When marked blood flow delay occurred, the
      perfused right ventricular myocardium became macroscopically anaemic (ischaemic).
      Over 75% narrowing of the major epicardial coronary artery was induced in six of
      the 15 pigs, and over 50% narrowing in 12, with marked blood flow delay with 100
      to 200 micrograms of acetylcholine. However, after intracoronary infusion of 10
      micrograms of nipradilol, acetylcholine induced narrowing in the epicardial major
      coronary artery was significantly reduced from 44-79% in control to 19-37%
      despite 200 micrograms of acetylcholine, though the time delay in coronary blood
      flow did not change significantly. By pretreatment with intracoronary isosorbide
      dinitrate (2.5 mg), the percent narrowing of the large coronary artery and the
      time delay in coronary blood flow were significantly reduced (narrowing from 32
      84% to 10-27%; time delay from 7.6-41.6 s to 2.7-22.7 s). Pretreatment with
      intracoronary bunazosin, an alpha 1 adrenoceptor antagonist (100 micrograms),
      showed no protective effect on narrowing of the epicardial major coronary artery
      or blood flow delay. CONCLUSIONS: Isosorbide dinitrate prevents coronary artery
      constriction induced by acetylcholine in swine. Nipradilol prevents large, but
      not small, coronary artery constriction, probably through a direct nitrate like
      vasodilating action.

PMID- 1982931
TI  - New thoughts on the evolution of hormone-receptor systems.
AB  - A possible pathway of the evolution of hormone-receptor systems has been
      discussed in light of the genomic potential hypothesis. Unlike the Darwinian
      system which is based on uninvestigatable chance events, the genomic potential
      hypothesis offers predictions based upon chemical determinism (boundary
      determinism). Accordingly, the production of highly specific protein-protein
      interactions between receptors and hormones, for example, are based upon the
      development of interacting components before the primordial chemistry was
      segregated by membranes. It is proposed that in addition to the primary structure
      (coding activity) a higher level of information exists in the genome which caused
      genomic products to function in a complementary fashion in living systems. The
      first steps in that direction have already been taken via experiments on sense
      and antisense peptides which may have specific relationships to each other. It is
      clear that I have not given an answer but I hope that I have touched upon certain
      aspects of a problem that can be illuminated better by a new and different
      approach to evolution. The hormone-receptor development was probably a powerful
      formative force in the development of macroorganisms, and its baffling complexity
      can only begin to find an explanation on the basis of structure/function
      relationships of the encoding material and its products.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1982932
TI  - Ontogeny of N-acetyltransferase activity rhythm in pineal gland of chick embryo.
AB  - 1. N-acetyltransferase was present in pineal glands of 14-day-old chick embryos
      though no rhythm either in LL, DD or LD 12:12 was observed in this age. 2. Daily
      rhythm in pineal NAT activity was found in 18-day-old embryos incubated under LD
      12:12 and LD 16:8 but no NAT rhythm was detected in DD or LL. 3. NAT rhythm
      persists for 2 days in constant darkness and it may be circadian in nature. 4.
      Presence of melatonin (85 +/- 8 pg/mg tissue) was detected in pineals of 18-day
      old chick embryos.

PMID- 1982933
TI  - Changes in serum protein lipid and electrolyte levels in rabbits at mid-altitude.
AB  - 1. The effects of mid-altitude on the profiles of total serum lipid, cholesterol,
      fibrinogen, albumin, Ca2+, Cl-, Na+ and K+ were investigated in rabbits for 22
      days. From 30 rabbits living at sea level 15 were exposed to 1170 m and 15 to
      2240 m altitude. 2. When compared with sea level values; total protein, albumin
      and K+ significantly decreased up to 5th day (P less than 0.01), then they
      gradually increased. 3. Total lipid, cholesterol, Ca2+, Cl- and Na+ levels
      elevated in 2nd day (P less than 0.01) then they gradually decreased to their sea
      level values. 4. It was concluded that the adaptation mechanisms begin at mid
      altitudes.

PMID- 1982934
TI  - Epidermal growth factor accelerates the intestinal cessation of macromolecular
      transmission in the suckling rat.
AB  - 1. The effects of EGF administered subcutaneously on the intestinal cessation of
      macromolecular transmission and sucrase development were investigated in suckling
      rats and compared with those on hydrocortisone-treated pups. 2. In the EGF
      treated pups, intestinal absorptive response of IgG was suppressed 50% whereas,
      the sucrase activity was not affected. In the hydrocortisone-treated pups, the
      absorptive response was inhibited completely, while sucrase activity was induced
      precociously. 3. The characteristics of intestinal cessation was morphologically
      observed at the jejunal epithelial cells in EGF and hydrocortisone-treated pups.
      4. These results suggest that EGF affects the maturation of gastrointestinal
      function in a manner different from that of glucocorticoid hormones.

PMID- 1982935
TI  - Implications of interscapular brown adipose tissue removal and sucrose
      overfeeding on the sympatho-adrenal activity and metabolic responses.
AB  - 1. The influence of sucrose overfeeding on the sympatho-adrenal (SA) and
      metabolic responses was studied in sham-operated (SHAM) rats and in those with
      interscapular brown adipose tissue (IBAT) removed. 2. Sucrose feeding
      significantly increased the SA activity, mobilized the free fatty acids (FFA),
      but did not change glucose homeostasis in sham-operated rats. 3. IBAT removal in
      control rats fed a stock diet modified the SA activity whereas the levels of both
      blood glucose and serum FFA were unchanged. 4. However, sucrose in rats void of
      IBAT potentiated the activity of sympathetic nervous system only and prevented
      the FFA rise, which is seen in sham-operated sucrose fed rats indicating that the
      enhanced level of serum FFA in these animals principally originated from the
      IBAT.

PMID- 1982936
TI  - Mineral content of the free-living nematode Turbatrix aceti and ruminant parasite
      Trichostrongylus colubriformis.
AB  - 1. The parasitic nematode Trichostrongylus colubriformis and free-living nematode
      Turbatrix aceti were examined for element content. 2. T. colubriformis contained
      significantly less phosphorus, potassium, manganese and boron than T. aceti. 3.
      T. colubriformis contained significantly more nitrogen and copper than T. aceti.
      4. Comparative study of the chemical composition of parasitic vs free-living
      nematodes may facilitate in vitro cultivation of the parasitic forms.

PMID- 1982937
TI  - The effect of heat exposure on blood chemistry of the hyperthermic rabbit.
AB  - 1. Two hours of exposure to heat stress, resulted in hyperthermia in rabbits
      (Oryctolagus cuniculus). 2. This was accompanied by a severe hypocapnia, partly
      compensated for by a significant decrease in bicarbonate (HCO3-) concentration.
      3. The severest hyperthermia (Tb = 43.5 degrees) was followed by a sharp
      decreased in both PaCO2 (to 20.2 torr) and HCO3- (to 9.2 mM/l), resulting in
      extreme metabolic acidosis (pH = 7.290). 4. The significant increase in serum
      osmolality (27%) is interpreted by the cumulative effect of increased electrolyte
      and metabolite concentrations. 5. The elevation in blood BUN, creatinine,
      globulin and GOT levels point to a possible damage to muscle cells by
      hypothermia. 6. The stable cholesterol and alkaline phosphatase levels, suggest
      that liver tissue was not damaged. 7. The dramatic increase in glucose from 103.8
      to 348.8 mg%, and the significant increase (from 22.0 to 39.9 mg%) in BUN,
      suggest a possible disability of the cells to metabolize carbohydrates,
      accompanied by a progressive proteolysis as an alternative process for energy
      production. 8. The data suggest that the emergence of muscle cell damage, severe
      hyperglycemia and acidosis under heat stress, precedes and amplifies the
      deteriorating effects of high Tb in heat stressed rabbits, which often lead to
      mortality.

PMID- 1982938
TI  - Muscle buffering capacity and dipeptide content in the thoroughbred horse,
      greyhound dog and man.
AB  - 1. Muscle buffering capacity (beta m) and dipeptide content were measured in
      locomotory muscles of the Thoroughbred horse, Greyhound dog and Man. 2. Beta m
      and carnosine contents were highest in the horse. Anserine was only found in dog
      muscle. 3. The higher beta m in horse and dog muscle, compared with man, appears
      to be predominantly due to higher muscle contents of histidine containing
      dipeptides in these species.

PMID- 1982939
TI  - Comparative studies of volume restoration following cold-stress induced swelling
      in renal tissues--I. Effects of ouabain, K+ free medium, colchicine and
      cytochalasin B on rat and rabbit kidney cortex slices.
AB  - 1. Cold-stress-induced swelling in rabbit and rat kidney cortex slices cannot be
      due to the sole inhibition of a Na+/K+ exchange system. In these tissues indeed,
      ouabain induces no swelling and an exchange of Na+ for K+ or a l/l basis.
      Inhibition of K+ extrusion at low temperature has also to be taken into
      consideration. 2. Volume restoration at 27 degrees C after cold-stress-induced
      swelling is inhibited by ouabain in rabbit slices, not in rat ones. The
      inhibition in rabbit slices is concomitant with an increase in Na+ at levels
      higher than equilibrium with the external medium. 3. Volume restoration does not
      seem to implicate colchicine or cytochalasin B sensitive processes.

PMID- 1982940
TI  - Comparative studies of volume restoration following cold-stress induced swelling
      in renal tissues--II. Effects of furosemide, amiloride and K+ permeability in
      rabbit cortex slices.
AB  - 1. Inhibition of volume restoration by ouabain in rabbit kidney cortex slices is
      related to an increase in Na+ concentration which may reach levels higher than
      equilibrium with the external medium. 2. The uphill accumulation of Na+ is not
      sensitive to amiloride and furosemide. It is dependent on the level of K+ in the
      external medium. 3. Bringing the slices from cold to normal temperature induces a
      large increase in Rb86 efflux. 4. It is concluded that the Na+ entry inhibiting
      volume restoration is driven by an increase in K+ expel occurring upon tissue
      rewarming.

PMID- 1982941
TI  - Costs of swimming measured at optimum speed: scale effects, differences between
      swimming styles, taxonomic groups and submerged and surface swimming.
AB  - 1. Data on swimming energy expenditure of 30 submerged and nine surface swimmers,
      covering different swimming styles and taxonomic groups, are selected from the
      literature. 2. The costs of transport at the optimum speed are compared and
      related to body mass and Re numbers. 3. Fish and turtles use relatively less and
      most surface swimmers slightly more energy than the other submerged swimmers; man
      and mink are poorly adapted to swimming. 4. The metabolic rate in W at optimum
      speed is approximately equal to the body mass in kg for fish and turtles and
      three times the mass figure for the other submerged swimmers.

PMID- 1982942
TI  - [Environment and genetics of endocrine polyoncoses. An aging bull model].
AB  - An old bull, it is said by those who know, can have his troubles. Included among
      these are vertebral osteosclerosis and ankylosing spondylosis--this stiffening up
      limite, rather than accentuates, the value and reproduction potential of a stud
      bull past prime. But associated with these abnormalities--and not seen in age
      matched cows of comparable breeds--are fascinating endocrine neoplasms that might
      suggest a pattern that could be productive as a model of human hereditary
      endocrine abnormalities. Adjacent to the thyroid gland in other vertebrates are
      ultimobranchial bodies, that are incorporated into the lateral thyroid lobes in
      primates as the parafollicular "C-cells" of the thyroid. These are the cells in
      man that give rise to medullary thyroid cancer and are associated with calcitonin
      secretion, useful as a tumor marker. In aging bulls of whatever breed, nearly
      half exhibit abnormality of these ultimobranchial bodies: 20% show hyperplasia,
      and 30% have frank neoplasia. These ultimobranchial tumors appear in bulls
      passing 6 1/2 years in age, and are absent in young bulls and all cows of any
      age. Calcitonin can be demonstrated in the ultimobranchial tumors from bulls, and
      secretion is stimulated by calcium infusion, though serum calcium remains normal.
      The ultimobranchial tumors themselves can range from hyperplasia through adenoma
      to metastasizing carcinoma--in fact, representing one of the commoner cattle
      cancers. Parathyroid glands taken from bulls with these ultimobranchial tumors
      initially show evidence of inhibited secretory activity and morphologic atrophy,
      but later go on to develop hyperplasia and, eventually, autonomy.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1982943
TI  - [The restriction polymorphism of the gene locus for human growth hormones in
      different populations of the USSR].

PMID- 1982944
TI  - The effect of exercise, diet restriction, and aging on the pituitary--adrenal
      axis in the rat.
AB  - The effects of calorie restriction, exercise, and aging on the pituitary-adrenal
      axis were studied in male Wistar rats from 12 to 28 months of age. There were 4
      experimental groups: sedentary, ad libitum fed (A); sedentary, diet restricted by
      feeding on alternate days (R); exercised by swimming on alternate days, ad
      libitum fed (AE); exercised as AE, diet restricted as R (RE). Pituitary-adrenal
      function was assessed by measuring serum ACTH and corticosterone concentrations,
      adrenal weight, hepatic glucocorticoid receptor concentration, and hepatic
      tyrosine aminotransferase (TAT) activity. Serum corticosterone concentration
      increased with age while serum ACTH decreased from 12 to 20 months of age and
      then increased thereafter. TAT activity decreased and receptor concentration
      remained constant with age. Adrenal weights increased with age; those of AE rats
      increased dramatically. Analyses for relationships between variables revealed a
      quadratic relationship between serum ACTH and corticosterone concentrations.
      There tended to be an inverse relationship between TAT activity and
      corticosterone concentration. These observations may be indicative of a loss of
      feedback loop integrity with aging. Neither calorie restriction nor exercise were
      able to maintain the integrity of pituitary-adrenal function during aging, though
      dietary restriction did slow age-associated decrements of TAT activity.

PMID- 1982945
TI  - [Pin-solder splinting of PT jacket crowns--a practical guide].

PMID- 1982946
TI  - Carrier detection and prenatal diagnosis in haemophilia A and B.
AB  - Sixty probable carriers of haemophilia from 25 families were studied by using
      coagulation phenotype and DNA analysis: 33 with haemophilia A and 27 with
      haemophilia B. Coagulation phenotype was based on factor VIII/IX assay and DNA
      analysis on the examination of restriction fragment length polymorphisms (RFLPs)
      within and closely linked to factor VIII or IX: 3 RFLP for factor VIII and 3 for
      factor IX. The comparison between the coagulation phenotype and RFLP analysis
      showed the misclassification of 15 females (6 for haemophilia A and 9 for
      haemophilia B). Four prenatal haemophilia A diagnosis were made by DNA analysis
      of chorionic villi, taken with a transcervical trophoblastic biopsy, between the
      18th and the 11th week.

PMID- 1982947
TI  - Plasma somatostatin-like immunoreactivity during growth-hormone-releasing hormone
      therapy in non-growth-hormone-deficient children.
AB  - To date, the effects of long-term growth hormone (GH)-releasing hormone [GHRH(1
      29)-NH2] treatment on the plasma concentrations of somatostatin-like
      immunoreactivity (SLI) remain undefined. In the present study, the effect of
      GHRH(1-29)-NH2 therapy on plasma SLI levels has been studied in 11 non-GH
      deficient children. The pattern of administration was 5 micrograms/kg body
      weight, given subcutaneously once every day. There was no significant change in
      plasma SLI levels after bolus injection of GHRH(1-29)-NH2 before and during
      GHRH(1-29)-NH2 therapy. However, plasma SLI rose in basal plasma and nocturnal
      sleep after 3 months of GHRH(1-29)-NH2 therapy and remained the same during 6
      months of treatment with GHRH(1-29)-NH2. The reason for this finding is
      uncertain, but an increase in SLI release from the enteroinsular axis is a
      possible explanation. The association of our findings with the role of the
      circulating SLI on nutrient homeostasis and the effects of GNRH on growth
      velocity is discussed.

PMID- 1982948
TI  - Rate limiting barrier to the penetration of ocular hypotensive beta blockers
      across the corneal epithelium in the pigmented rabbit.
AB  - The objective of this study was to determine the rate-limiting layer(s) in the
      penetration of ocular hypotensive beta blockers across the corneal epithelium in
      the pigmented rabbit. The beta blockers studied were, in order of increasing
      lipophilicity, atenolol, timolol, levobunolol, and betaxolol. Corneal drug
      penetration was evaluated over 240 min using the isolated pigmented rabbit cornea
      in the modified Ussing chamber. Reversed phase HPLC was the analytical
      methodology. The cornea was preexposed to 20-100 microM digitonin for 15 min in
      an attempt to strip off selective layers of the corneal epithelium. The corneal
      epithelium offered no resistance to the penetration of the very lipophilic
      betaxolol. The major resistance to the corneal penetration of the moderately
      lipophilic timolol and levobunolol was in the superficial cell layers of the
      corneal epithelium. For the hydrophilic atenolol, the resistance to corneal drug
      penetration appeared to extend across all corneal epithelial cell layers. The
      above findings suggest that the number of corneal epithelial cell layers limiting
      the corneal penetration of ocularly administered drugs is inversely related to
      drug lipophilicity.

PMID- 1982949
TI  - Tolerance to long-term feeding of isolated peanut lectin in the rat: evidence for
      a trophic effect on the small intestines.
AB  - Previously we have shown that rats fed a diet containing raw peanut meal as the
      sole source of protein exhibited alterations in enzyme activity and composition
      of certain organs. To determine the effects of isolated peanut lectin on body
      growth and on the intestines, experiments were carried out in weanling, male,
      Sprague-Dawley rats fed a casein diet incorporated with purified peanut lectin at
      three levels, 0.004, 0.04, and 0.2% for 23 days. Body weight gain was normal with
      all three diets. In rats fed the 0.004 and 0.04% peanut lectin, there were no
      changes in any of the small intestinal mucosal parameters under study. However,
      in rats consuming the 0.2% peanut lectin diet, the proximal, mid, and distal
      third regions of the small intestines all showed marked increases in mucosal
      weight, protein, and DNA contents, but without altered villus morphology. Of the
      3 brush border enzymes studied, namely maltase, gamma-glutamyltranspeptidase, and
      alkaline phosphatase, none was altered in activity in any region, suggesting that
      microvillus integrity was normal. These results are similar to the reported
      actions of red kidney bean lectin on the intestines. We conclude that peanut
      lectin at up to 0.2% of the diet does not inhibit food intake or growth of
      weanling rats and is apparently trophic for all areas of the small intestines.

PMID- 1982950
TI  - Diffusible factor(s) from adult rat sciatic nerve increases cell number and
      neurite outgrowth of cultured embryonic ventral mesencephalic tyrosine
      hydroxylase-positive neurons.
AB  - Dissociated embryonic rat ventral mesencephalon containing the developing A8-A10
      dopamine (DA) neurons was cultured alone or in the presence of a 10 mm segment of
      adult rat sciatic nerve that had been explanted and maintained in separate
      culture for 72 hours prior to introduction to mesencephalic cultures. Nerve
      segments were contained in a co-culture basket, so that midbrain cells and nerve
      shared medium but were not in physical contact. The number and morphology of
      cultured DA neurons was assessed via immunocytochemistry for tyrosine hydroxylase
      (TH). Co-cultures of ventral midbrain tissue and nerve exhibited an increased
      number of TH-positive neurons, with larger neuronal perikarya, and increased
      length and complexity of neurites, than cultures of midbrain tissue alone.
      Increased number and growth of TH-positive neurons was obtained with as little as
      2 days of exposure to nerve. This evidence suggests that a diffusible, soluble
      factor(s) from sciatic nerve can enhance the number and development of TH
      positive neurons detected in cultures of embryonic ventral mesencephalon.

PMID- 1982951
TI  - [The place of the screening method in the early discovery and treatment of
      cryptorchism].
AB  - According to modern concepts, only early operative treatment of cryptorchidism
      may guarantee good results. This has been proven by the results obtained by the
      authors, who for five years have on mass prophylactic examination (1984-1988)
      searched for cryptorchidism in children attending kindergartens in the town of
      Tolbukhin. In this way the authors succeeded in realising highest operative
      activity in the age from 3 to 4 years.

PMID- 1982952
TI  - A silent regulatory gene cfaD' on region 1 of the CFA/I plasmid NTP 113 of
      enterotoxigenic Escherichia coli.
AB  - A DNA sequence, homologous to the cfaD gene of CFA/I region 2, was identified on
      CFA/I region 1. This sequence is designated cfaD'. It differs from the cfaD gene
      in containing two deletions and a stop codon. The cfaD' sequence therefore can
      only encode a truncated CfaD-like protein. The CfaD protein may be a DNA binding
      protein and functions as a positive regulator of CFA/I fimbriae expression. A
      regulatory function for the cfaD' is not likely since deletion of the cfaD'
      sequence does not affect production of CFA/I fimbriae in E. coli K-12 strains.
      That the cfaD' sequence is present on CFA/I wild-type plasmids isolated from
      CFA/I strains of different serotypes, obtained at various geographical locations,
      suggests, however, that this DNA region is not completely without a function.

PMID- 1982953
TI  - Characterization of pili expressed by Haemophilus ducreyi.
AB  - Twelve strains of Haemophilus ducreyi isolated primarily from chancroid outbreaks
      in North America were examined for the presence of pili by transmission electron
      microscopy. We identified piliated cells in 10 of the 12 strains. Pilin extracts
      were prepared from the mechanically sheared cells of the 12 H. ducreyi strains as
      well as the stably piliated H. influenzae strain R890 and its non-piliated parent
      R906. Pili were present in 12 out of 12 H. ducreyi extracts and in the R890
      extract but not in the R906 preparation. Pili were purified by cycles of
      differential pH solubilization and crystallization. In SDS-PAGE, the preparation
      consisted predominantly of a protein whose apparent relative molecular mass was
      24,000 (24 k), and an electron micrograph showed that the preparation contained
      pili. Three H. ducreyi strains were passed 52 times on agar plates, and extracts
      prepared from these strains contained pili. There was no evidence of binding of
      erythrocytes obtained from nine mammalian and avian species to colonies of one of
      the stably piliated H. ducreyi strains. We conclude that H. ducreyi expressed
      pili, that the relative molecular mass of the pilin monomer was 24 k, that pilus
      expression was not readily lost in passage and that H. ducreyi pili may not bind
      to an erythrocyte receptor.

PMID- 1982954
TI  - Activation of striatal tyrosine hydroxylase by in vivo electrical stimulation:
      comparison with cyclic AMP-mediated activation.
AB  - These studies were carried out to characterize the activation of rat striatal
      tyroxine hydroxylase produced by depolarization of the medial forebrain bundle
      and to evaluate the possible role of cyclic AMP as a mediator of this activation.
      The enzymatic properties of tyrosine hydroxylase following in vivo depolarization
      were compared to those produced by treatment of striatal synaptosomes with
      dibutyryl cyclic AMP (dbcAMP). Similar effects were observed with regard to
      enzyme distribution, altered sensitivity to dopamine-induced inhibition, and
      activity as a function of tyrosine concentration. However, differences between
      the two treatments were also apparent. First, treatment with dbcAMP shifted the
      pH optimum from 6.2 to 7.0. In contrast, electrical stimulation decreased the
      rate of decline in activity as the pH was increased above the optimum, but did
      not shift the pH optimum. Second, plots of tyrosine hydroxylase activity versus
      cofactor concentration revealed two enzyme forms for both control and
      electrically stimulated preparations. However, dbcAMP treatment converted the
      enzyme to a single high affinity form. These results can be explained by one of
      the following: (1) cyclic AMP is the sole mediator of enzyme activation, but does
      not produce a maximally activated enzyme following in vivo depolarization, (2)
      cyclic AMP is only one of several mediators involved or (3) cyclic AMP is not
      involved in depolarization-induced activation, with activation occurring via the
      mediation of other intracellular messengers, such as calcium.

PMID- 1982955
TI  - Mechanism of Alzheimer's disease: arguments for a neurotransmitter-aluminium
      complex implication.
AB  - The authors are convinced that in Alzheimer's disease, as in Down's syndrome and
      Guam-Parkinson dementia, one may find an alteration in blood brain barrier
      transfer and a resultant imbalance in mineral metabolism. Metals, such as
      aluminium, which in vivo yield stable complexes with aspartic and glutamic acids
      act as previously been clearly shown with glutamic acid; they cross the blood
      brain barrier, and are deposited in the brain. The authors explain how amyloid
      protein or neurofibrillary tangles could well be produced by aluminium complex
      formation. Within the brain, in the form precisely of aluminium complex, L
      glutamic acid is consequently unable to detoxify ammonia from neurons and to
      produce L-glutamin. Accumulation of ammonia is subsequently responsible for the
      neuronal death, affecting each and every neurotransmitter system.

PMID- 1982956
TI  - Neurofilament protein-triplet immunoreactivity in distinct subpopulations of
      peptide-containing neurons in the guinea-pig coeliac ganglion.
AB  - A battery of polyclonal and monoclonal antibodies raised against the triplet of
      identified neurofilament protein subunits was used to investigate neurofilament
      protein immunoreactivity in neurons of the guinea-pig coeliac ganglion. Using
      optimal conditions of fixation and tissue processing for each antibody we found
      that only 20% of the postganglionic sympathetic neurons in the guinea-pig coeliac
      ganglion contain neurofilament protein-triplet immunoreactivity. Double labelling
      with neurofilament protein-triplet antibodies raised in different species
      demonstrated that all of these antibodies labelled the same population of
      neurons. Double labelling using mouse monoclonal antibodies against neurofilament
      proteins in combination with rabbit polyclonals to neuronal markers showed that
      neurofilament protein-triplet immunoreactivity is restricted to specific
      chemically coded subpopulations of noradrenergic neurons. Approximately 52% of
      neurons in the ganglion contain neuropeptide Y and are presumed vasomotor neurons
      projecting to blood vessels in the submucosa of the small intestine. Virtually
      none of the neuropeptide Y-containing neurons were labelled with neurofilament
      protein-triplet antibodies. Neurons that contain somatostatin (21%) project to
      the submucous ganglia of the small intestine. Approximately two-thirds of neurons
      containing somatostatin are immunoreactive for the neurofilament protein-triplet.
      The other postganglionic neurons in the ganglion (27%) project to the myenteric
      plexus of the small intestine and do not contain either neuropeptide Y or
      somatostatin. Approximately a quarter of these neurons were labelled with
      neurofilament protein-triplet antibodies. These results suggest that the
      neurofilament protein-triplet may not be an intrinsic component of the
      cytoskeleton of all neurons. Furthermore the idea of a chemical coding of neurons
      should be extended to cytoskeletal proteins. The finding that these neurofilament
      proteins are confined to specific neuronal subpopulations has important
      implications for the search for a role of the neurofilament protein-triplet in
      neurons, for the interpretation of classical neurohistological silver
      impregnation techniques which appear to stain only neurofilament protein-triplet
      containing neurons, as well as for neuropathological conditions that may involve
      these proteins in disease processes.

PMID- 1982957
TI  - Parkinsonism in monkeys produced by chronic administration of an endogenous
      substance of the brain, tetrahydroisoquinoline: the behavioral and biochemical
      changes.
AB  - We have examined the effect of chronic administration of a probable endogenous
      dopaminergic neurotoxin, tetrahydroisoquinoline (TIQ, 20 mg/kg per day, s.c. for
      up to 104 days), on squirrel monkeys. Chronically administered TIQ produced motor
      symptoms similar to parkinsonism in squirrel monkeys even after 7 days'
      discontinuation of TIQ and the symptomes were alleviated remarkably by levodopa
      treatment. Biochemical analysis of the brains of TIQ-treated monkeys revealed
      significant decrease in dopamine (DA) and total biopterin (BP) concentrations,
      and tyrosine hydroxylase (TH) activity in the substantia nigra, and these
      biochemical changes were not reversed by 7 days following the termination of
      chronic administration of TIQ. TIQ was identified in the brain (caudate-putamen)
      of saline-injected control monkeys by gas chromatography-mass spectrometry. The
      endogenous levels of TIQ in the caudate-putamen was about 0.15 micrograms/g, and
      increased up to 3-4 micrograms/g, 1 day as well as 7 days following termination
      of TIQ administration.

PMID- 1982958
TI  - Ovarian steroids block the isoproterenol-induced elevation of pineal melatonin
      production in the female rat.
AB  - Changes in pineal indole metabolism during the estrous cycle, as well as in
      response to estrogen administration, were studied in female rats. Tyrosine
      hydroxylase (TH) activity, norepinephrine (NE) and indoleamine levels were
      determined by high-performance liquid chromatography (HPLC). Pineal melatonin was
      measured by radioimmunoassay (RIA). Both 5-hydroxytryptamine (5-HT) and melatonin
      levels, but not TH activity or NE content, were reduced during proestrus. Ovarian
      hormones blocked the isoproterenol-induced elevation of pineal melatonin, and
      reduced 5-HT levels in ovariectomized rats. These results suggest that an
      estrogen-induced inhibition of the pineal response to adrenergic stimulation,
      could be responsible for the reduction in pineal melatonin production occurring
      during the proestrus stage of the rat estrous cycle.

PMID- 1982959
TI  - Tyrosine hydroxylase mRNA in the dopaminergic neurons of young adult and aged
      mice by in situ hybridization.
AB  - Tyrosine hydroxylase (TH) mRNA in the dopaminergic neurons of the substantia
      nigra (SN) and the ventral tegmental area (VTA) in young adult and aged mice was
      detected and quantitated using in situ hybridization. Using 3H-labeled antisense
      RNA complementary to TH mRNA, these studies demonstrate the presence of TH mRNA
      in dopaminergic neurons of the SN and the VTA. Alternate sections stained
      immunocytochemically using TH-specific antiserum demonstrated that the neurons
      containing TH mRNA also contained TH protein. Quantitative analysis of the number
      of silver grains present over the dopaminergic neurons of the SN and VTA revealed
      no statistically significant difference between the two age groups. The results
      suggest that TH gene expression in dopaminergic neurons of the SN and VTA is not
      different in young adult and aged mice.

PMID- 1982960
TI  - NMDA receptor-independent epileptiform activity induced by magnesium-free
      solution in rat amygdala neurons is blocked by CNQX.
AB  - The effect of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a specific non-N
      methyl-D-aspartate (non-NMDA) receptor antagonist, on NMDA-independent
      epileptiform activity induced by Mg2(+)-free medium was studied in rat
      basolateral amygdala (BLA) neurons using intracellular recording techniques.
      Twenty to 30 min after switching to Mg2(+)-free medium, spontaneous and evoked
      epileptiform activity were observed in 16 out of 18 amygdala slices. Superfusion
      of D-2-amino-5-phosphonovalerate (D-APV), a selective NMDA receptor antagonist,
      reduced the duration of epileptiform activity by an average of 83%. However,
      there was a residual depolarizing component which remained in the presence of D
      APV. This D-APV-resistant component could be completely blocked by CNQX
      suggesting that it is mediated by non-NMDA receptors.

PMID- 1982961
TI  - Late low magnesium-induced epileptiform activity in rat entorhinal cortex slices
      becomes insensitive to the anticonvulsant valproic acid.
AB  - We investigated time-dependent changes in low magnesium-induced epileptiform
      activity in combined rat entorhinal cortex/hippocampal slices with extracellular
      recording techniques. While in area CA3 short interictal discharges are generated
      without any major changes in activity during prolonged recording periods, initial
      tonic clonic ictaform events in the entorhinal cortex may change with time. We
      observed often a transition into a state of recurrent tonic activity without any
      clonic afterdischarges. Alternatively, seizures could stay in the clonic
      discharge mode for the rest of the experiment. These different seizure states
      were not equally affected by the anticonvulsant valproic acid. While the early
      clonic tonic discharges in the entorhinal cortex and the interictal like activity
      in area CA3 were effectively suppressed by valproic acid (VPA) the late recurrent
      tonic seizure discharge state was unaffected by the drug. It was, however, still
      sensitive to the N-methyl-D-aspartate (NMDA) receptor antagonist 2
      aminophosphonovalerate. These findings point to seizure-induced changes in
      neuronal interaction in rat entorhinal cortex.

PMID- 1982962
TI  - Biphasic effects of magnesium on the [3H]N-(1-(2-thienyl)cyclohexyl)-3,4
      piperidine binding in the rat cerebral cortex.
AB  - Mg2+ at micromolar concentrations greatly enhanced [3H]N-(1-(2
      thienyl)cyclohexyl)-3,4-piperidine ([3H]TCP) binding to well-washed rat cortical
      membranes, whereas [3H]TCP binding was inhibited by Mg2+ at concentrations higher
      than 1 mM. In the presence of either L-glutamate (10 microM) or glycine (10
      microM), 30 microM Mg2+ caused further stimulation of [3H]TCP binding, suggesting
      that a high-affinity site for Mg2+ is distinct from the glutamate or glycine
      binding site. These findings indicate that Mg2+ acts on at least two different
      recognition sites, e.g. a novel high-affinity site for Mg2+ which stimulates
      [3H]TCP binding and the Mg2+ recognition site located within the ion channel.

PMID- 1982964
TI  - Genotoxic effect of N-nitroso derivatives of five beta-adrenergic blocking
      agents.

PMID- 1982963
TI  - Some pharmacological properties of perhydro-1,4-thiazepine and perhydro-1,2,5
      dithiazepine derivatives.
AB  - Some newly synthesized perhydro-1,2,5-dithiazepine derivatives have
      antihistaminic, anticholinergic and spasmolytic properties. One perhydro-1,4
      thiazepine derivative, compound 3, produces also a weak local anesthetic effect.
      The activity of the investigated compounds is lower than that of reference
      compounds; diphenhydramine, antazoline and papaverine.

PMID- 1982965
TI  - Age-related changes of GHRF and somatostatin cell signalling pathways operating
      in the rat pituitary gland.

PMID- 1982966
TI  - Cerebrovascular disease and k-opioid receptors in the rabbit.

PMID- 1982967
TI  - Kainate receptor activation stimulate release of glutamate, alanine and glycine.

PMID- 1982968
TI  - Alpha-2 adrenoceptors modulating [3H]noradrenaline release in rat brain cortex
      are not identical to alpha-2B subtype.

PMID- 1982969
TI  - NMDA receptor activation mediates glutamate and aspartate release from rat
      striatum: prevention by MK-801.

PMID- 1982970
TI  - Conflict-behaviour and temporal discrimination performance in the rat: comparison
      between alprazolam and various conventional benzodiazepines.

PMID- 1982971
TI  - Microdialysis. Introduction.

PMID- 1982972
TI  - A clinical perspective on microdialysis.

PMID- 1982974
TI  - Pharmacodynamics of antibiotics-consequences for dosing. Proceedings of a
      symposium. Stockholm, June 7-9, 1990.

PMID- 1982975
TI  - Mechanism of phenotypic tolerance of nongrowing pneumococci to beta-lactam
      antibiotics.
AB  - Within minutes after the onset of deprivation of an essential nutrient, all
      bacteria develop resistance to lysis by beta-lactam antibiotics, a phenomenon
      termed phenotypic tolerance. Two phases of this process were identified in
      pneumococci and the activity of the major autolysin, an N-acetylmuramyl-L-alanine
      amidase, was studied in each phase. Autolysin was detectable by
      immunofluorescence in a uniform distribution over the surface of growing
      pneumococci, but became progressively depleted during amino acid deprivation.
      Lysis of nongrowing cells by beta-lactam antibiotics could be reconstituted by
      addition of exogenous autolysin during the first 80 minutes of starvation (Phase
      I) but not thereafter (Phase II). Similarly, Triton X-100 or deoxycholate lysed
      nongrowing cells in Phase I but not Phase II. Cell wall isolated from Phase II
      cells was found to be more resistant to hydrolysis by the autolysin in vitro than
      that from growing cells. Lysis of growing cells could also be inhibited by
      incorporation of a pulse of nonhydrolysable cell wall or autolysin deficient cell
      wall into the growth zone. These results suggest that phenotypic tolerance in
      nongrowing pneumococci involves rapid loss or disengagement of autolysin
      molecules from their in situ attack-sites (Phase I) followed by a second slower
      process that involves a progressive change in the cell wall structure to a form
      less susceptible to hydrolysis by the autolysin (Phase II).

PMID- 1982976
TI  - [Morpho-functional characteristics of the adenohypophysis in cardiovascular
      pathology].
AB  - Morphologic examination of the adenohypophysis of 46 subjects who died from
      cardiovascular diseases has shown a restructuring of the gland, including changes
      in its nonspecific signs and alterations typical of certain cardiovascular
      conditions. Analysis of the ratios between various types of endocrine cells and
      different types of basophil tropocytess in health and disease has revealed
      variability of these parameters in cardiovascular diseases and in various types
      of the same disease. Fluctuations in adenohypophysis cellular composition are
      explained by specific features of the pathogenesis of these conditions.

PMID- 1982973
TI  - Evidence that lack of brain dopamine during development can increase the
      susceptibility for aggression and self-injurious behavior by influencing D1
      dopamine receptor function.
AB  - 1. Lesch-Nyhan disease has a defined neurological lesion that is accompanied by
      abnormal motor function, aggression and self-injurious behavior. 2. The dopamine
      deficiency in Lesch-Nyhan disease has been modelled by destroying dopamine
      containing neurons in neonatal rats with 6-hydroxydopamine. 3. Because D1
      dopamine antagonists will block self-injurious behavior induced by L-DOPA in
      neonatal-6-OHDA-lesioned rats, D1-dopamine antagonists are proposed as a
      potential therapy for aggression and self-injurious behavior in patients with
      these symptoms. 4. The determination that the drug SCH-12679, which exhibited
      effectiveness against aggressiveness in mentally retarded patients, is a D1
      dopamine antagonist supports the view that new D1-dopamine antagonists being
      developed will be an effective therapy for some types of aberrant behavior in
      this population.

PMID- 1982977
TI  - Somatostatin in rat retina: localization by in situ hybridization histochemistry
      and immunocytochemistry.
AB  - In order to analyse the mRNA-protein relationships of somatostatin containing
      neurons in the rat retina, we have used a combined method with in situ
      hybridization histochemistry using radio-labeled oligodeoxyribonucleotides
      complementary for rat somatostatin mRNA and immunocytochemistry using antiserum
      for somatostatin protein. We found double labeled amacrine cells in the innermost
      and outermost laminae of the inner nuclear layer as well as the displaced
      amacrine cells in the ganglion cell layer in the retina. Some cells in the inner
      nuclear layer had high levels of somatostatin mRNA. Radially immunostained
      interplexiform fibers were observed adjacent to the amacrine cells with high
      level of somatostatin mRNA. These data suggest the site of synthesis of
      somatostatin and post-translational migration of this neuropeptide within the rat
      retinal tissue.

PMID- 1982978
TI  - [Densitometric analysis of aminopeptidase M activity in small intestine mucosa in
      piglets experimentally infected with Isospora suis].
AB  - In gnotobiotical and conventional piglets infected a day post partum (DPP) with
      oocysts of the coccidium Isospora suis, densitometrical analysis of the activity
      of aminopeptidase M (EC.3.4.11.2; APM) was performed in the area of microvillous
      zone of the small intestine. Piglets were infected with different infection doses
      of oocysts (100,000 oocysts) in gnotobiotical piglets and 200,000 oocysts in
      conventional piglets). In infected gnotobiotical piglets, the APM activity was
      studied in the period from the 3rd to 11th day after infection (DAI) and in
      infected conventional piglets in the period of to the 2nd to 10th day after
      infection (DAI). Control piglets, in the group of the gnotobiotical animals at
      the age of 2 to 5 days in the group of the conventional animals at the age of 4
      to 7 days, had different APM activity in the microvillous zone of the intestinal
      mucosa. It was stated that the microvillous zone of the intestinal mucosa gained
      higher values in control conventional piglets (+7.01 mean values of density). In
      infected gnotobiotical piglets the density fall of the reaction product of APM
      was demonstrated already on the third day with further marked reduction of APM
      density on the 4th day after infection in the whole small intestine with
      predominance of the persisting APM activity in ileum. Even despite the slight
      increase in the density of the reaction product of APM in the period from the 5th
      to 7th DAI (the highest increase in APM density on the 6th DAI), a further
      decrease of the activity was recorded again on the 8th and namely the 9th DAI in
      the whole small intestine (the lowest value of density was found in the rear
      jejunum), the ileum mucosa being affected, too. A slightly higher density of the
      reaction product of APM was found in the duodenum. On the 10th DAI the APM
      density started to change and on the 11th DAI in the duodenum and in the middle
      jejunum it even reached higher values in comparison with the control data. Some
      differences were proved in the infected conventional piglets in comparison with
      the development of the APM activity in the small intestine mucosa in the infected
      gnotobiotical piglets. On the 3rd and 4th DAI APM defect occurred in the whole
      small intestine, with APM density prevailing in the ileum mucosa (like in the
      group of infected gnotobiotical piglets). The second period of decrease in APM
      activity lasted for almost four days (6th to 9th DAI).(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 1982979
TI  - [The second session of the Global Commission on AIDS in Brazzaville, the Congo 8
      10 November 1989].

PMID- 1982980
TI  - Neurosurgical aspects of epilepsy. Proceedings of the Fourth Advanced Seminar in
      Neurosurgical Research of the European Association of Neurosurgical Societies.
      Padova, May 17-18, 1989.

PMID- 1982981
TI  - Involvement of granulocyte factor (GF) in receptor-triggered stimulation of
      lymphocytes and neutrophils.
AB  - Granulocyte factor derived from the specific granules of polymorphonuclear
      neutrophils affects mitogen--and alloantigen--induced proliferation of human
      lymphocytes "in vitro". A dual pattern of GF effect was noted: inhibition of
      mitogen induced lymphocyte proliferation in higher concentrations and
      costimulatory activity in lower concentrations of GF. GF induced the lymphocyte
      proliferation in combination with phorbol ester (PMA) or anti-CD2 monoclonal
      antibodies (mAb) with PMA. Other combinations of anti-CD2 and anti-CD3 mAb with
      GF do not augment the proliferation. The comitogenic activities of GF are
      associated with IL-2 production and IL-2R expression. Specific binding of
      labelled GF to stimulated lymphocytes suggests that it may recognize the specific
      molecule expressed only an activated cells. GF diminishes the zymosan-induced
      granulocyte stimulation, but GF acts as a stimulator of granulocyte O2
      production. GF may recognize common targets on leukocytes. Leukocyte adhesive
      glycoproteins may be such putative targets.

PMID- 1982982
TI  - [Aminopeptidase activity in populations of human blood mononuclear cells].
AB  - The aminopeptidase N (AP N, EC 3.4.11.2) is an ectoenzyme of the plasma membrane,
      playing presumably an important role in the regulation of immunological
      processes. The specific activities of Ala-pNA and Leu-pNA cleavage (per cell) are
      distributed in monocytes T- and non-T-lymphocytes in a proportion of 1:0.2:0.25
      and 1:0.17:0.18, respectively. The capacities of Ala-pNA and Leu-pNA hydrolysis
      in the total fraction T- and non-T-cells are distributed as 1:0.8 and 1:0.7,
      respectively. The main part of Ala-pNA cleavage was shown to be caused by AP N on
      the basis of the KM-value (0.5 mmol/l), the activation by CO2+ ions and the pH
      optimum (7.0-7.5). The Leu-pNA cleavage is dependent on CO2+ and DTT and distinct
      from the classical cytosolic leucyl aminopeptidase.

PMID- 1982983
TI  - Phase-I study of diacetyl-splenopentin (BCH 069).
AB  - BCH 069 is a new synthetic pentapeptide with thymic hormone-like activity. Two
      groups of patients received 50 mg BCH 069 or placebo by subcutaneous injection
      for 4 weeks 3 times weekly. The third group of patients received 50 mg BCH 069 by
      intravenous injection for 6 weeks 3 times weekly. The therapy was carried out
      during the peak of the pollen season. We observed the following clinical and
      biochemical activities of BCH 069: - flush symptom with a feeling of heat during
      intravenous administration of 50 mg/10 ml but not during 50 mg/20 ml, - decrease
      of triglyceride serum level, - decrease of SGOT- and SGPT serum levels, -
      increase of lipase serum level, - decrease of hemoglobin. - All changes of the
      biochemical parameters were not outside of the normal laboratory values. The
      disease-specific inflammatory changes were not seen in the intravenously treated
      group. The administration route is very important for the clinical side effect
      but not for drug induced biochemical changes. It can be concluded that BCH 069 is
      a well tolerated drug.

PMID- 1982984
TI  - Pharmacologic desensitization for dental phobias: clinical observations.
AB  - The elimination of the extreme fear reported by dental phobic patients
      traditionally involves psychologic interventions such as systematic
      desensitization. Observations resulting from a conscious sedation approach, as
      outlined in two case histories, suggest that a desensitization phenomena is
      occurring. This pharmacologic desensitization appears to mimic elements of
      systematic desensitization. Optimal management of fearful patients may sometimes
      require conjunctive support from both dental behavioral scientists and dental
      anesthesiologists.

PMID- 1982985
TI  - Hydrocortisone regulation and expression of tyrosine aminotransferase gene in
      various tissues of rat.
AB  - Treatment of Wistar rats with a single dose of hydrocortisone acetate resulted in
      a transient induction of tyrosine aminotransferase (TAT) in the liver. TAT
      activity and the level of TAT mRNA increased 4-6 h after addition of
      hydrocortisone acetate (induction phase) and declined thereafter (deinduction
      phase). TAT activity and TAT mRNA failed to respond to readdition of fresh
      hydrocortisone acetate during the deinduction period, but cycloheximide treatment
      at this period increased the level of TAT mRNA. Hydrocortisone acetate alone and
      cycloheximide alone or after hydrocortisone acetate treatment stimulated the rate
      of TAT gene transcription. TAT displayed a low activity in the rat heart, brain
      and kidney, and was not induced by hydrocortisone acetate in these tissues. In
      addition to liver, TAT mRNA was found in heart, brain and kidney, but in the
      latter three tissues its amount was about one tenth only as in the liver, which
      was consistent with different levels of TAT activity. Upon hydrocortisone acetate
      treatment the TAT mRNA levels in brain and heart remained unchanged.

PMID- 1982986
TI  - DQ beta restriction fragment length polymorphism in insulin dependent diabetes
      mellitus.
AB  - HLA DQ beta restriction fragment length polymorphisms (RFLP's) were compared in
      43 patients with insulin dependent diabetes mellitus (IDDM), 51 healthy first
      grade relatives of IDDM patients and 27 controls without IDDM heredity in their
      families. We were able to demonstrate an association between the presence of a 12
      kb BamHI restriction fragment (p less than 0.001) and 12 kb/4 kb (p less 0.01) or
      12 kb/4.4 kb (p less than 0.001) BamHI fragment combinations and IDDM. But for
      these fragments and fragment combinations we also found increased frequencies in
      the healthy first grade relatives of IDDM patients. That means for the evaluation
      of the importance of the characterised "risk fragments" in practice it is
      necessary to follow up the manifestation of IDDM in this risk group.

PMID- 1982987
TI  - Bgl II-restriction fragment length polymorphism of the insulin receptor gene in
      patients with type-II diabetes mellitus.
AB  - As an approach to estimate the involvement of the insulin receptor gene in the
      etiopathogenesis of type-II diabetes mellitus we determined the distribution of
      the alleles of a restriction fragment length polymorphism of this gene (Bgl II
      RFLP) in a group of type-II diabetics. The patients had been characterized by
      insulin and C-peptide values during OGTT and insulin receptor binding indices.
      The difference in allelic distribution to a healthy control group (10% "+"-allele
      in diabetics versus 18% in control persons), was not significant in chi 2
      analysis.

PMID- 1982988
TI  - Identification of carriers by screening for delta F508 deletion in a multi
      generation cystic fibrosis family.
AB  - Samples from 30 members of a french cystic fibrosis (CF) family had to be typed
      with probes for restriction fragment length polymorphisms (RFLPs) known to be
      linked to the CF gene, to fulfill the expectations of twenty-two low-risk
      relatives who were asking for carrier testing. Classical linkage-disequilibrium
      data between KM-19 and XV-2c polymorphisms and the CF locus were not informative
      enough for some individuals, and other RFLPs had to be analyzed to determine
      which chromosomes carried the deficient gene in the family. We report the
      retrospective screening for delta F508 mutation in this extended family to
      illustrate the drastic improvements that the direct detection of the major
      mutation responsible for CF has on genetic counselling of relatives of patients
      with cystic fibrosis.

PMID- 1982989
TI  - T cells in bullous pemphigoid. Presence of activated CD4+ T cells at the basement
      membrane zone in pre- and peri-bullous skin.
AB  - Bullous pemphigoid (BP) is an auto-immune blistering skin disease associated with
      the presence of autoantibodies directed to BP antigens located at the basement
      membrane zone of the dermal-epidermal junction. The present study was designed to
      test for the involvement of cellular immune mechanisms in the pathogenesis of
      blister formation. An immunohistochemical analysis of the lesional, peri
      lesional, and pre-lesional mononuclear cell infiltrates, performed in 7 BP
      patients, revealed the following observations: 1) all the skin biopsies contained
      a high percentage of mononuclear cells within the inflammatory cellular
      infiltrate; 2) T cells (CD3+, CD45RO+), with a phenotype of activated helper T
      cell (CD4+, CD25+) were consistently found; 3) T cells were found beneath the
      bullae but, more importantly, also at the dermal-epidermal junction in close
      contact with the basement membrane zone in pre- and peri-bullous lesions. These
      results show that activated T cells are found at the early phase of the onset of
      BP lesions and suggest that they could play a role, in association with
      autoantibodies, in the pathogenesis of bulla formation.

PMID- 1982990
TI  - The kinetics of migration of murine CD4 and CD8 lymphocytes in vivo.
AB  - Lymphocytes from the mesenteric lymph nodes (MLN) of mice were enriched for CD4+
      and CD8+ T cell populations, labeled with (51Cr) sodium chromate, and transferred
      to the bloodstream of syngeneic recipients. The time course of migration of the
      labeled cells from the blood to the secondary lymphoid organs of the recipients
      was investigated. CD4+ and CD8+ subpopulations differed in their profile of
      appearance in different lymphoid organs. Computer assisted analysis of the
      observations was used to obtain quantitative estimates of the rate of clearance
      of the lymphocytes from the blood into the tissues, and the rate of departure of
      the cells from the tissues. In the spleen, CD4+ lymphocytes were cleared from the
      blood about one and one-half times faster than CD8+ lymphocytes, but the CD8+
      cells were retained longer. Inguinal nodes (IN), MLN, and Peyer's patches (PP)
      showed a consistent ability to clear CD4+ cells from the blood at a rate
      approximately 2.5 x greater than that for CD8+ cells, but the retention of the
      lymphocytes in these tissues varied with lymphocyte phenotype and the organ
      concerned. CD4+ lymphocytes were retained longer in PP and MLN than in IN,
      whereas CD8+ cells were retained longer in IN and MLN nodes than in PP. We
      conclude that the rate of clearance of lymphocytes into secondary lymphoid organs
      from the blood varies in a regular way with T cell phenotype and that organ
      specific sorting of T subpopulations also proceeds after the cells are admitted
      to the tissues.

PMID- 1982991
TI  - Modifications to improve the effectiveness of restriction fragment length
      polymorphism typing.
AB  - A streamlined and effective method for RFLP analysis of DNA has been developed.
      Southern transfers are accomplished by alkali blotting DNA onto positively
      charged nylon membranes. The prehybridization step has been eliminated. The
      hybridization solution is composed of three cost-effective reagents: 7% SDS, 10%
      PEG, and phosphate buffer. By using probes that hybridize to variable number of
      tandem repeat loci, and RFLP analysis of one to two micrograms of genomic DNA can
      be achieved within five working days under normal working hours. With longer
      autoradiographic exposures, as little as 20-100 ng of human genomic DNA is
      sufficient for analysis.

PMID- 1982992
TI  - Agarose gel electrophoresis of linear genomic DNA in the presence of ethidium
      bromide: band shifting and implications for forensic identity testing.
AB  - We demonstrate that agarose gel electrophoresis of linear duplex DNA in the
      presence of ethidium bromide has a marked effect on the mobility of genomic DNA
      fragments detected by Southern hybridization. Mobility shifts of greater than 6%
      of the actual molecular weight were detected when different amounts of the same
      DNA sample were analyzed in 1.0% agarose gels containing 0.5 micrograms ml-1
      ethidium bromide. For forensic applications, shifts of this magnitude could
      complicate the task of comparing restriction fragment length polymorphism
      profiles and introduce a degree of uncertainty to allele frequency population
      databases.

PMID- 1982993
TI  - [Rapid identification of Neisseria meningitidis using the gammaglutamyl
      aminopeptidase test].

PMID- 1982994
TI  - [IX International Symposium of Morphology Sciences. September 9-13, 1990, Nancy,
      France. Abstracts].

PMID- 1982996
TI  - Abstracts of the 30th meeting of the Association for Eye Research including the
      annual meeting of the European Club for Ocular Fine Structure. Montpellier,
      France, 4-7 October 1989.

PMID- 1982995
TI  - [Screening and evaluation on predictive factors in lithium carbonate maintenance
      treatment of manic-depressive disorders].
AB  - The prophylactic effect of lithium carbonate was studied prospectively in 95
      patients with recurrent manic-depressive disorders. Maintenance lithium treatment
      started at the stage of recovery after previous episodes lasting for 20-24
      months. Of all the 95 patients, 55 cases (57.9%) were responders, with no relapse
      during the follow-up period; whereas the other 40 cases (42.1%) were non
      responders, having at least one relapse occurred from 4 to 12 months after the
      index episode. Of the parameters studied, (1) minor primary episode; (2) higher
      lithium RBC/plasma ratio (greater than 0.4); (3) increase of plasma calcium level
      during lithium treatment; (4) extraversion-cycloid personality featured by EPQ
      have higher predictive sensitivity and specificity (greater than 70%) and maybe
      used as the core predictive factors for long-term outcome in lithium treatment.
      The other parameters, the age of unset, frequency of episodes, euphoric and
      grandiose symptoms, clinical respond of first lithium anti-episode medications
      and lithium clearance can also be used as corresponding predictive factors in
      selecting cases for long-term lithium treatment.

PMID- 1982997
TI  - The molecular basis for inhibition of adipose conversion of murine 3T3-L1 cells
      by retinoic acid.
AB  - The effect of retinoic acid (RA) on the adipose conversion of 3T3 cells has been
      studied. Differentiation of 3T3-L1 cells was initiated by addition of 0.5 mM
      methylisobutylxanthine, 0.3 microM dexamethasone and 10 micrograms/ml insulin
      (MDI) to confluent monolayers of preadipocytes for 48 h. During this time, the
      cells underwent DNA replication and cell division prior to the expression of
      adipose specific genes. RA administration had no apparent effect on the rate or
      extent of cell growth, cell division, or DNA replication. However, RA treatment
      concomitant with MDI addition inhibited triacylglycerol accumulation (I0.5 = 6
      nM) and the accumulation of the differentiation-dependent mRNAs encoding the
      adipocyte lipid-binding protein (ALBP) and stearoyl-CoA desaturase 1 (SCD1). No
      inhibition occurred with RA addition either prior to or after MDI treatment.
      Runoff transcription revealed that the inhibitory effects of RA occurred at the
      level of transcription and were persistent. Cells treated with RA during the MDI
      regimen did not appreciably transcribe ALBP or SCD1 mRNAs several days following
      RA withdrawal. The effects of RA were specific for differentiation-dependent
      transcripts: 10(-6) M RA did not inhibit expression of the mRNAs encoding beta
      tubulin or glutamine synthase. Examination of immediate-early transcription
      factor expression during the MDI regimen revealed that RA mediated an elevated,
      prolonged expression of c-Jun mRNA accompanied by diminished expression of c-Fos
      and Jun-B mRNAs. Given the previously demonstrated role of transcription factor
      AP-1 in ALBP gene expression, our results suggest that the initiation of
      expression of this and other adipocyte-specific genes during adipose conversion
      is regulated by the relative composition of transcription factor AP-1.

PMID- 1982999
TI  - P-glycoprotein and drug resistance in acute leukemias and in the blastic crisis
      of chronic myeloid leukemia.
AB  - The aim of this work is to evaluate the relationship between P-glycoprotein
      expression in circulating blasts and clinical response in patients suffering from
      acute lymphoblastic leukemia, acute non-lymphoblastic leukemia, and chronic
      myeloid leukemia in either lymphoid or myeloid blastic crisis. The results
      obtained show that: a) patients whose blasts express P-glycoprotein are resistant
      towards protocols including Doxorubicin, Daunorubicin, Etoposide, Mithramycin,
      Vincristine; b) P-glycoprotein can be expressed constitutively in some cases; c)
      P-glycoprotein does not appear to be the only mechanism responsible for
      resistance towards anthracyclines and Etoposide.

PMID- 1982998
TI  - Considerations underlying the use of autologous blood stem cell transplantation
      in malignancies.

PMID- 1983000
TI  - Autologous blood stem cell transplantation in hematologic malignancies.
AB  - Circulating stem cells (CSC) are well documented in animals and humans. Though
      their function in normal conditions remains obscure, autologous CSC seem capable
      of restoring hemopoiesis after myeloablative treatment. With cell separators CSC
      may be harvested in adequate number, and collection may be further improved
      giving chemotherapy and/or GM-CSF that mobilize stem cells into the circulation.
      Due to the high number of progenitor cells infused, hematologic reconstitution is
      more rapid with CSC than with marrow cells. Autologous blood stem cell
      transplantation (ABSCT) is increasingly employed in a variety of hematologic
      malignancies and in some solid tumors. CSC allow transplantation in patients
      previously irradiated on the sites of harvest or with marrow tumor involvement,
      and probably decrease the risk of infection by shortening the duration of post
      graft aplasia. Their use is also encouraged by a belief that, along with CSC, a
      large number of immunocompetent cells are infused that may exert an anti-tumor
      effect. A lower tumor contamination of CSC as compared to marrow is an attractive
      matter, but remains to be demonstrated. Standardization of cell cloning assays,
      identification of monoclonal antibodies to recognize the surface antigens
      expressed on progenitor cells, and definition of advantages of ABSCT are items of
      future work.

PMID- 1983001
TI  - Coronary artery bypass grafting without cardiopulmonary bypass.

PMID- 1983002
TI  - Differences in non-MHC restricted cytotoxic activities of human peripheral blood
      lymphocytes after transfusion with allogeneic leukocytes or platelets possessing
      class I and/or class II MHC molecules.
AB  - MHC-unrestricted cytotoxic activity of peripheral blood lymphocytes (PBL) from 4
      6 healthy donors was investigated before and after transfusion with allogeneic
      leukocytes or platelets. Natural killer and lectin-dependent cellular
      cytotoxicity (LDCC) of PBL was tested against K562 and Raji target cells in a 4-h
      and 16-h 51Cr-release assay, respectively. After allotransfusion with leukocytes,
      we found increased cytotoxic activity of each donor's PBL against all the three
      targets on day 3 or 7. The highest non-specific cytotoxic activity was detected
      against the relatively NK resistant Raji target cells. The increase of cytotoxic
      activity was lowest against the LDCC target (PHA-treated Raji) cells. On the
      contrary, no changes in cytotoxic activity against any targets were observed
      after allotransfusion with platelets (possessing class I HLA antigens but no HLA
      class II molecules). Our results suggest that HLA class II molecules, presumably
      by inducing immune responses, are essential for activation/generation of non
      specific killing of tumor targets after leukocyte transfusion. Thrombocytes,
      known to be less immunogenic than leukocytes, are not effective in in vivo
      enhancing of non-specific cytotoxicity. Cellular activation of PBL following
      leukocyte allotransfusion was confirmed by detection of elevated serum neopterin
      and beta-2-microglobulin levels on day 3. This was not the case after platelet
      allotransfusion. In addition, the expression of ICAM-1 antigen (as a molecule
      involved directly in MHC-unrestricted cytotoxicity) was also found to be
      increased in two donors' PBL on day 3 after leukocyte transfusion in contrast to
      transfusion with platelets.

PMID- 1983003
TI  - Structural characteristics of the 5' region of the human ICAM-1 gene.
AB  - The ICAM-1 glycoprotein, one of the major cellular adhesion molecules, exhibits a
      diverse and highly regulated tissue distribution. To better understand the
      regulatory mechanisms underlying its particular expression pattern, we have
      cloned the ICAM-1 gene from human leukocyte libraries. By hybridization with
      various DNA probes derived from different regions of the ICAM-1 cDNA, several
      clones were identified and isolated. Clone HWB 3R1, containing a 15kb DNA insert,
      was selected for further characterization. The HWB 3R1 clone hybridized with
      probes corresponding to the 3' as well as the 5' region of the ICAM-1 cDNA and
      gave rise to ICAM-1 expression after transfection into the ICAM-1 deficient MJP17
      melanoma cell line. The identity of the expressed ICAM-1 was verified by reaction
      with five different monoclonal antibodies specific for ICAM-1. Sequence analysis
      of about 1.2kb of DNA around the ATG start codon revealed putative binding sites
      for various transcription factors situated in the 5' untranslated region as well
      as within the first intron. These include SP-1, AP-1 and NF-kB binding sites as
      well as interferon and retinoic acid responsive elements.

PMID- 1983004
TI  - Effect of N-acetyl-aspartyl-glutamate (Naaga) on in-vitro leukotriene synthesis
      by macrophage cell line P388D1.
AB  - The magnesium salt of N acetyl-aspartyl glutamic acid (Naaga), used in ophthalmic
      allergies, is a synthetic dipeptide analogue of a natural peptide found in
      mammalian brains. It has been shown in vitro that Naaga inhibits complement
      activation, mast-cell degranulation and leukotriene anaphylactic release. In
      order to verify Naaga's action on leukotriene production, we used the macrophage
      cell line P388D1 activated by calcium ionophore A23187. Leukotriene determination
      was performed by high-performance liquid chromatography. It was found that Naaga
      inhibits 15 to 80% macrophage eicosanoid secretion (10(-9) M to 10(-2) M), acting
      mainly on LTC4-D4-E4 synthesis. Naaga was as potent as the leukotriene inhibitor
      nordihydroguaiaretic acid and as dexamethasone in this model. This inhibition of
      leukotriene secretion could partially explain the in-vivo antiallergic effects of
      Naaga.

PMID- 1983006
TI  - Do we need a dopaminergic agent in the management of the critically ill?
AB  - 1. The stimulation of dopaminergic receptors is in principle attractive to
      increase urine and sodium excretion in patients with compromised renal blood
      flow. 2. However, a protective role of dopaminergic agents on renal function has
      not been well established. Most of the trials have been performed with dopamine,
      a substance which can have vasoconstrictive properties, even at relatively low
      doses in the critically ill patient. 3. Perhaps other dopaminergic agents without
      alpha-adrenergic effects such as dopexamine could be more advantageous.
      Randomized, prospective, controlled clinical studies should be performed to test
      the hypothesis that dopaminergic agents can reduce the incidence of acute tubular
      necrosis in critically ill patients.

PMID- 1983005
TI  - Efficacy and safety of ibopamine in congestive heart failure.
AB  - 1. Ibopamine is a new orally active inodilator, which is developed for the
      treatment of congestive heart failure (CHF). We treated 13 patients with moderate
      to severe CHF already on maximal conventional medication with ibopamine and
      studied its effects on haemodynamic parameters, exercise capacity, plasma
      norepinephrine (NE) and ventricular arrhythmias on ambulatory ECG monitoring. 2.
      Both cardiac and stroke volume index increased significantly after ibopamine (33%
      and 35% resp.). These changes were accompanied by a fall in systemic vascular
      resistance without changes in heart rate or blood pressure. During
      cardiopulmonary exercise testing, both maximal oxygen consumption and exercise
      time increased. Plasma NE levels were not significantly changed after ibopamine.
      Using the Morganroth criteria for proarrhythmia on ambulatory ECG monitoring, two
      patients showed proarrhythmia from ibopamine, which was not clinically relevant,
      but four patients had a decrease in ventricular arrhythmias. 3. This study
      suggests that ibopamine elicits favourable effects on haemodynamics and exercise
      tolerance in patients with CHF. During ibopamine treatment, there appears to be
      no increase in ventricular arrhythmias.

PMID- 1983007
TI  - Renal dopamine and tubular DA-1 receptors in the regulation of sodium excretion.
AB  - 1. We have performed studies in rats with selective DA-1 receptor agonists
      fenoldopam and dopexamine which show that activation of tubular DA-1 receptors by
      these agents results in natriuresis and diuresis. 2. In pentobarbital
      anaesthetized rats, an acute increase in sodium intake produced by volume
      expansion (5% body weight) with isotonic sodium chloride led to pronounced
      increases in sodium and water excretion. These natriuretic and diuretic responses
      were accompanied by significant increases in urinary dopamine excretion and could
      be attenuated by the selective DA-1 receptor antagonist, SCH 23390. 3.
      Intravenous infusion of atrial natriuretic factor produced hypotension,
      bradycardia and an increase in sodium and water excretion. The natriuretic and
      diuretic response to the peptide was not accompanied by any changes in urinary
      dopamine excretion but it was attenuated by SCH 23390 and the dopa decarboxylate
      inhibitor, carbidopa. 4. These results show that renal tubular DA-1 receptors can
      be activated by selective agonists, which subsequently leads to natriuresis and
      diuresis. During acute volume expansion, there is an increased production of
      renal dopamine, which contributes to the natriuretic response via activation of
      tubular DA-1 receptors. Finally, we discovered that endogenous dopamine plays a
      permissive role in the full expression of the renal effects of the atrial
      natriuretic factor.

PMID- 1983008
TI  - Physiological modulation of renal function by the renal dopaminergic system.
AB  - 1. The renal dopaminergic system is a potentially important regulator of sodium
      homeostasis and kidney function. 2. We have presented evidence that dopamine acts
      as a paracrine substance at DA-1 and DA-2 receptors in the physiological control
      of renal function. 3. Much more information is required regarding basic cellular
      mechanisms and the functional regulation of the system so that the role of renal
      dopamine can be placed clearly in context with other established hormonal
      regulatory systems.

PMID- 1983009
TI  - Effect of pramipexole, a dopamine-1/dopamine-2 receptor agonist, on sodium
      excretion and blood pressure in spontaneously hypertensive rats.
AB  - 1. Abnormalities of the renal dopaminergic system have been implicated in the
      pathogenesis of hypertension in the spontaneously hypertensive rat (SHR). 2. Both
      DA-1 and DA-2 receptors are present in renal tubules and blood vessels. DA-1
      receptors mediate the renal vasodilatory and natriuretic effects of DA but the
      contribution of DA-2 receptors to these effects is not known. 3. We therefore
      studied the effect of a novel and selective DA-1 and DA-2 agonist, pramipexole,
      on MAP, glomerular filtration rate (GFR), urine flow (V), absolute (UNaV) and
      fractional sodium (FeNa) excretion in 9-18-week-old SHR. Wistar-Kyoto rats (WKY)
      served as control. 4. Pramipexole given intravenously (1, 10, 100 micrograms kg
      body wt-1 min-1) decreased MAP in a dose-related manner to a greater extent in
      SHR (n = 5) than WKY (n = 6) such that at the highest dose of pramipexole, MAP
      was similar in both groups. Pramipexole did not alter GFR in either WKY or SHR.
      Pramipexole increased V in a dose-related manner in both WKY and SHR. At 100
      micrograms pramipexole kg body wt-1 min-1, V increased eightfold in both SHR and
      WKY. In contrast, pramipexole increased UNaV to a greater extent in WKY (5.1
      fold) than SHR (3.7-fold). 5. These studies show a differential effect of
      pramipexole on renal function and MAP in SHR and WKY. Pramipexole has a more
      potent blood pressure lowering effect in SHR than in WKY. However, the
      natriuretic effect of pramipexole was greater in the WKY than in the
      SHR.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1983010
TI  - Differential modulation of the renal proximal tubular DA-1 receptor by Gpp(NH)p
      and sodium in the spontaneously hypertensive rat.
AB  - 1. In the normotensive rat (WKY) the guanine nucleotide, Gpp(NH)p, and sodium
      reduced the ability of the dopaminergic agonist fenoldopam to compete for the
      [3H]-SKF-38393 (dopamine-1 agonist) binding to the renal proximal tubular DA-1
      receptors. 2. In the spontaneously hypertensive rat (SHR) Gpp(NH)p failed to
      reduce the affinity of fenoldopam for [3H]-SKF-38393 binding to renal tubular DA
      1 receptors. 3. Sodium reduced the affinity of fenoldopam for [3H]-SKF-38393
      binding in the SHR renal proximal tubular cells, but to a lesser extent than the
      WKY. 4. We conclude that the SHR has a defective DA-1 receptor or Gs/receptor
      coupling which interferes with the ability of Gpp(NH)p to act on the DA
      receptor/G protein complex.

PMID- 1983011
TI  - Development of dopaminergic drugs for the chronic treatment of congestive heart
      failure.
AB  - 1. The search of orally active dopaminergic drugs for the chronic treatment of
      congestive heart failure has followed two different approaches. 2. On the one
      hand, a selective DA-1 receptor agonist, such as fenoldopam, has been
      investigated as an agent developed for the stimulation of vascular and tubular DA
      1 receptors in the kidney. On the other hand, orally active prodrugs were
      synthetized with the aim of mimicking the full pattern of dopaminergic and
      adrenergic actions of intravenous dopamine. 3. Ibopamine, the diisobutyric ester
      of N-methyldopamine, has shown effects comparable to those of dopamine in various
      animal models and in clinical investigations. Furthermore, patients suffering
      from mild or severe congestive heart failure were shown to benefit from ibopamine
      treatment in a number of therapeutic trials. 4. Limited experience is currently
      available on other prodrugs, such as docarpamine and Sim 2055, i.e. the 4-0
      phosphate ester of N-methyldopamine. The latter is an analogue of ibopamine
      designed for a preferential delivery of N-methyldopamine in the kidney. 5. Based
      upon some additional studies with levodopa, the results suggest that a
      combination of DA-1 and DA-2 agonistic activity is a desirable feature of a new
      drug, since it appears suitable to provide vasodilation while counteracting the
      neurohumoral abnormality of congestive heart failure.

PMID- 1983012
TI  - Insecticidal activity of carbosulfan (OMS 3022) and pyraclofos (OMS 3040) against
      mosquitoes.
AB  - Carbosulfan (OMS 3022), a carbamate and pyraclofos (OMS 3040), an organophosphate
      were evaluated for their biological activity against vector mosquitoes, both in
      laboratory and field conditions. Carbosulfan (25% EC), was found to be active
      against adults and immatures of Culex quinquefasciatus, Anopheles stephensi and
      Aedes aegypti. The LD values for adults were 6.65, 5.19 and 8.35 micrograms/cm2
      and LC 50values for immatures were 5.4 X 10(-5), 1.6 X 10(-4 and 5.4) X 10(-4)
      50mg/1 respectively. Pyraclofos (50%) showed neither larvicidal nor adulticidal
      activities. The residual effect of carbosulfan (25% WP) on cement, thatch and mud
      surfaces at 400 mg (ai)/m2 lasted for 3, 16 and 21 weeks respectively. In the
      field, carbosulfan at 2.00 kg (ai)/ha resulted in complete control of C.
      quinquefasciatus larvae for a period of one week in cement tanks and less than a
      week in other polluted water bodies, such as cesspits, cesspools and drains.
      Pyraclofos was not effective at a dose of 2.00 kg (ai)/ha in any of the habitats.

PMID- 1983013
TI  - Epidemiology of Brugia malayi infection and its co-existence with Wuchereria
      bancrofti in and around Sillaberia PHC, District Midnapur, West Bengal.
AB  - Of 2186 persons investigated in thirteen villages of Sillaberia PHC, 19 were
      found to be infected with Brugia malayi and only one person harboured
      microfilaria (mf) of Wuchereria bancrofti. Similarly 41 persons exhibited signs
      and symptoms of chronic filariasis. The mf and disease rates percent worked out
      to be 0.914 and 1.87 respectively. The earliest ages showing mf and disease
      manifestations were 3 and 11 respectively. The mean mf density ranged from 2 to
      12.2 per 20 cumm of blood. The male and female ratio in terms of mf carriers and
      chronic cases worked out to be 1.4:1 and 1:2 respectively. The entomological
      collections revealed a high ten man hour density (163.20) in case of Culex
      quinquefasciatus and comparatively much lower in case of Mansonia (Mansonioides)
      annulifera (47.51) and Mansonia (Mansoni oides) uniformis (23.83) respectively.
      The infection and infectivity rates in case of Mansonia (Mansonioides) annulifera
      were 6.1 and 1.2 per cent respectively.

PMID- 1983014
TI  - Prevalence of Wuchereria bancrofti infection in some coastal villages of Ganjam,
      Orissa.
AB  - The endemicity of filariasis was assessed in 42 villages of coastal Keluapalli
      PHC in Ganjam District of Orissa. Prevalence was found to vary greatly between
      extreme coastal and subcoastal villages. The infection was non existent in 12
      coastal villages. Age and sexwise distribution of filariasis cases have been
      analysed and presented.

PMID- 1983015
TI  - Classical taxonomy of mosquitoes--a memorial to John N. Belkin.
AB  - The major contributions of John N. Belkin to the field of mosquito systematics
      are noted. Hallmarks of his publications are presented and his hypotheses about
      the evolution, speciation, competition, distribution and classification of
      mosquitoes are summarized. The current status of the field of mosquito
      systematics is examined. It is argued that mosquito systematics is still largely
      at the alpha taxonomy level, that at best only 25-50% of mosquito species are
      known, and that we have not even begun to develop a natural classification for
      the Culicidae. It is concluded that there will be little improvement in the
      status of mosquito taxonomy unless there is increased support for systematics.

PMID- 1983016
TI  - Evaluation of 1-octen-3-ol as an attractant for Coquillettidia perturbans,
      Mansonia spp. and Culex spp. associated with phosphate mining operations.
AB  - Field studies were conducted in phosphate mined areas of Polk County, FL, to
      determine the responses of mosquitoes produced as a result of mining operations
      to octenol and carbon dioxide. There was a highly significant response of all
      species except Culex erraticus and Anopheles quadrimaculatus to CO2. Also, a
      significant negative octenol response was shown for An. quadrimaculatus.
      Coquillettidia perturbans, Mansonia titillans and Cx. salinarius had an increased
      response to octenol relative to no attractant. There was a slightly negative
      interactive effect between octenol and 500 cc/min CO2 for Anopheles spp. and
      Culex (Melanoconion) spp. Both Cq. perturbans and Ma. titillans showed a
      significant synergistic enhancement in catch with octenol supplemented CO2 when
      compared with CO2 alone. However, their response to CO2 was not significantly
      different at 2 release rates (200 and 500 cc/min). There was a slightly greater
      than additive effect for the combination of octenol and CO2 for Cx. nigripalpus.

PMID- 1983017
TI  - ETOC and lambdacyhalothrin: new pyrethroid mosquito adulticides.
AB  - Two new pyrethroids, ETOC and lambdacyhalothrin, showed considerable promise
      against organophosphorus-resistant adults of Culex tarsalis in laboratory tests.
      In field trials using nonthermal aerosols, applications of both compounds
      resulted in effective swaths of up to one-half mile. At the highest
      concentrations evaluated, residues on alfalfa foliage were less than 0.2 ppm at 1
      h. Residues declined greatly by 24 h and could not be detected at 48 or 72 h.

PMID- 1983018
TI  - Efficacy of Bacillus sphaericus formulations against Psorophora columbiae larvae
      in small rice plots.
AB  - Bacillus sphaericus formulations were evaluated against Psorophora columbiae
      larvae in small rice plots. All formulations tested provided good control
      (greater than 84%) for all rates tested at 2 days posttreatment. At 10 days
      posttreatment, fair control (greater than 70%) was recorded for ABG-6232 (0.184
      kg/ha), ABG-6262; 27-242-BA (0.766 and 2.298 liters/ha), and ABG-6262; 29-293-BA
      (2.298 liters/ha). At 7 days posttreatment mortality was below 66%. Control did
      not exceed 27% at 15 days posttreatment for any formulation tested. Application
      rates for all formulations tested had little relationship with observed
      mortality, and control levels often were greater at the lower dosages tested.
      Bacillus sphaericus provided an effective means for controlling Ps. columbiae,
      but additional research is needed to determine the lower limit of effective
      treatment dosages and spore persistence in the rice field environment.

PMID- 1983019
TI  - Quantitative field studies on a carbon dioxide chemotropism of mosquitoes. 1953.

PMID- 1983020
TI  - An improved model of a battery-powered aspirator.
AB  - Detailed instructions are provided to modify a commercially available, battery
      powered, leaf/grass blower into a portable, hand-held aspirator for collecting
      adult mosquitoes and other small dipterans. Directions are given also to convert
      paper cups into interchangeable collection containers for use with the aspirator.

PMID- 1983021
TI  - Body size variation of Culiseta morsitans in relation to vector potential for
      eastern equine encephalomyelitis virus.
AB  - Variation in the body size of wild Culiseta morsitans collected from
      Massachusetts was examined. No significant size variation was detected at any
      time during the collection period, nor was there a significant size difference
      between parous and nulliparous mosquitoes. We conclude that size variation in
      this species does not affect survivorship, an important aspect of vectorial
      capacity.

PMID- 1983022
TI  - A collapsible mosquito cage for field use.
AB  - The relatively inexpensive collapsible field cage described in this article has
      proven extremely practical for entomology work in distant locations. Frequent
      field use and continuous employment in a modest laboratory for more than a decade
      attests to the strength and durability of the design.

PMID- 1983023
TI  - Tests of Sabethes cyaneus leg paddle function in mating and flight.
AB  - Both sexes of the mosquito Sabethes cyaneus have conspicuous midleg paddles of
      unknown function. These paddles are displayed prominently by males during
      courtship. However, we found that paddle removal reduced successful mating of
      females, not males. Males without paddles approached and courted females
      normally, but females without paddles were rarely approached by males. Paddle
      removal appeared not to alter flight, and paddleless females oviposited in the
      manner characteristic of Sabethes, suggesting that the paddles do not aid in
      hovering or rapid reverse flight. We conclude that paddles of females are used in
      attracting males but that their function in males remains undetermined.

PMID- 1983024
TI  - Culiseta minnesotae and further notes on Aedes aegypti in Rhode Island.
AB  - Culiseta minnesotae is reported as a state record in Rhode Island. Follow-up
      surveys for Aedes aegypti after its initial isolation in 1985 have failed to
      recover additional specimens.

PMID- 1983025
TI  - Literature references for mosquitoes and mosquito-borne diseases. 1990--Part 4.

PMID- 1983026
TI  - [Plasma catecholamine response to tracheal intubation after midazolam and
      vecuronium in elderly patients with hypertension].
AB  - This study was undertaken to determine whether midazolam alleviates
      sympathoadrenal response evoked by tracheal intubation in elderly patients with
      hypertension. Anesthesia was induced with midazolam in a sleep dose followed by
      vecuronium 0.1 mg.kg-1. Heart rate and blood pressure were recorded before, 1 and
      3 minutes after induction with intubation. Free and total catecholamine (CA) in
      plasma were measured at each time. Dopamine, norepinephrine and epinephrine (EN)
      were determined using fluorescence derivatization with diphenylethylenediamine by
      HPLC. Although heart rate and diastolic pressure rose in some degree 1 min after
      intubation, free and total CA concentrations did not increase during study
      period. Free and total EN levels decreased significantly 3 min after intubation.
      The absence of elevation in plasma CA concentrations, especially in free CA,
      which is physiologically active, would contribute to produce circulatory
      stability on laryngoscopy and tracheal intubation. However, the mystery of why
      hyperdynamic state was produced without the increase in CA concentrations remains
      to be solved, even though it occurred for a short period of time.

PMID- 1983027
TI  - Electron microscopic observation of Branhamella catarrhalis.
AB  - The hemagglutination (HA) test was done on 85 strains of Branhamella catarrhalis,
      isolated from sputum of patients with respiratory infections; 53% were HA
      positive strains. Three HA positive and three HA negative strains were selected
      and were observed under the electron microscope. The bacterial cell wall appeared
      to be lobulated and its total thickness was about 38 nm. The nuclear region
      consisted of whorls or fibrils and dense bodies. Five strains were fimbriated and
      one strain was nonfimbriated. The size of fimbriae was about 68 nm in length and
      4.5 nm in width. The fimbriae of Branhamella catarrhalis were densely arranged
      and peritrichous in distribution. There was no change of fimbriation between
      broth and agar cultures.

PMID- 1983028
TI  - [Adenylate cyclase response to beta-adrenergic agonists in heart and brown
      adipose tissue].
AB  - Some sympathomimetic compounds (i.e. BRL37344) increase brown adipose tissue
      (BAT) thermogenesis with minimal cardiac effects. They act through an "atypical"
      beta-adrenergic receptor (beta-AR). Since beta-AR responses involve Adenylate
      Cyclase (AC) activation, we investigate the AC answer to isoproterenol and
      BRL37344 in rat plasmamembranes of heart (beta 1-ARs) and BAT (atypical beta
      ARs). AC dose-response curves were obtained by incubating membrane fractions with
      different concentrations of isoproterenol and BRL37344 (1 nM-100 microM) at 25
      degrees C for 15 min. In our study BRL37344 is 40-times more potent than
      isoproterenol in stimulating AC activity of BAT (EC50s: BRL37344 = 0.02 microM,
      isoproterenol = 0.7 microM). Furthermore it is more potent in stimulating BAT AC
      than heart AC (BRL37344 EC50 ratio heart/BAT = 38). However on BAT membranes,
      BRL37344 intrinsic sympathomimetic activity (ISA) vs. Isoproterenol is 0.87.
      Since isoproterenol and BRL37344 show a similar ISA for BAT respiration and
      lipolysis, we may argue that AC maximal activity is not required for maximal
      lipolytic and thermogenic responses.

PMID- 1983029
TI  - Measurement of the receptor turnover using an irreversible inactivating method.
      Theoretical assumptions, limitations and practical realization.
AB  - Recently it has become possible to characterize turnover of different receptors
      using the irreversible receptor inactivating agent N-ethoxycarbonyl-2-ethoxy-1,2
      dihydroquinoline (EEDQ). The mechanism of the EEDQ-evoked inactivation is due to
      creation of highly reactive mixed carbonic anhydrides from carboxyl groups, which
      react with a sterically accessible nucleophilic groups (e.g. free alpha-amino
      groups) of receptor peptides. The aim of this review is to describe basic
      theoretical and practical analyses in the receptor turnover measurement. The
      synthesis and degradation of receptors were shown as zero-order and first-order
      processes, respectively. Having made the above assumption it is very simple to
      characterize the receptor turnover in a culture tissue. However, a more
      complicated situation arises when EEDQ is used to assess an "ex vivo" (in vivo)
      receptor turnover. Furthermore, details which emerge during an analysis of the
      results of "ex vivo" receptor turnover measurements are discussed.

PMID- 1983031
TI  - Application of catastrophe theory to corneal swelling.
AB  - Stromal swelling in human, cat, and rabbit cornea is biphasic, interpretable as
      an elementary cusp catastrophe proposed by Thom, with t* = log t and Q* = log Q
      (stromal charge Q, time t) as control parameters, and H0.5 (hydration H) as the
      state variable. A thermodynamic potential with two attractor regions, each with a
      local minimum, governs corneal stromal swelling. Transitions follow a 'saturation
      convention' whereby the second minimum is preferred upon availability. Corneal
      swelling is an example of a space-equivalent unfolding, where the transition
      plane moves in time. It is proposed that the transition plane coincides with the
      uncoupling of interfibrillary linkages or 'springs' in the corneal stroma, and is
      associated with a critical hydration of ca. 10 kg H2O per kilogram dry mass, and
      stromal charge ca. 1 x 10(-7) mol electrons.

PMID- 1983032
TI  - Gene duplication and concerted evolution of the GPDH locus in natural populations
      of Drosophila melanogaster.
AB  - The sn-glycerol-3-phosphate dehydrogenase (GPDH, EC 1, 1, 1, 8) locus of
      Drosophila melanogaster is polymorphic with respect to the number of tandemly
      duplicated genes in natural populations. The duplicated genes were cloned and the
      nucleotide sequences were determined. The duplication deletes both the first and
      second exons and has a size of 4500 b.p. The fact that there is no sequence
      variation at the junction point of the duplicated units among strains suggests a
      single origin for the duplication event. Comparison of the nucleotide sequences
      among the duplicates indicates that the frequent transfer of genetic information
      occurs from one to the other of the duplicates on the same chromosome either by
      gene conversion or by unequal crossing over. Because the GPDH duplication is
      partial and therefore a kind of pseudogene, the observed polymorphism of the
      number of tandemly duplicated GPDH genes appears to have been driven mainly by
      random genetic drift.

PMID- 1983030
TI  - Light modulates dopamine-regulated Walsh inhibitor activity and dopamine
      dependent cyclic AMP accumulation in the rabbit retina.
AB  - The effect of various dopaminergic agents and related drugs on the activity of
      the heat-stable inhibitor of cyclic AMP (cAMP)-dependent protein kinase (Walsh
      inhibitor) and on cAMP accumulation was studied in retinas of light- and dark
      adapted rabbits. Both in dark- and light-adapted rabbits low doses of apomorphine
      increased the retinal Walsh inhibitor activity; high doses of the drug decreased
      the Walsh inhibitor activity in dark-adapted rabbits, but were without effect in
      light-adapted animals. S-Sulpiride antagonized the effect of low doses of
      apomorphine on the Walsh inhibitor activity, and, in contrast to haloperidol
      (which was effective), did not affect the action of a high apomorphine dose.
      Selective agonists of dopamine (DA) D2-receptor, quinpirole and bromocriptine,
      increased the retinal Walsh inhibitor activity in both light- and dark-adapted
      animals, a selective D1-agonist, SKF 38393, decreased the inhibitor activity in
      dark- and did not significantly modify it in light-adapted animals. In in vitro
      experiments, carried out in the presence of theophylline, DA and apomorphine
      increased cAMP accumulation in pieces of the rabbit retina through activation of
      D1-receptors. The action of DA, apomorphine, and SKF 38393, was significantly
      stronger in retinas of dark- than of light-adapted animals. Forskolin stimulated
      cAMP accumulation in a concentration-dependent manner, producing at 100 microM
      increases of cAMP levels by approximately 5-fold. DA and SKF 38393 did not
      significantly modulate the action of 10 microM forskolin, whereas apomorphine
      slightly decreased the forskolin effect. Of the two selective D2-receptor
      agonists, bromocriptine slightly decreased, and quinpirole had no effect on the
      forskolin action. The characteristics of the specific binding of [3H]spiroperidol
      were essentially the same in the retinas of dark- and light-adapted rabbits. Our
      data suggest that in light-adapted animals the D1-receptors, or the effector
      mechanisms for regulation of the Walsh inhibitor activity, may be desensitized.
      Our results suggest also that in the rabbit retina there are probably no D2
      receptors coupled negatively to adenylate cyclase, although a pharmacologically
      similar class of DA receptors seems to be involved in regulation of the Walsh
      inhibitor activity (in a way independent on environmental lighting).

PMID- 1983033
TI  - Antifertility effects of neem (Azadirachta indica) oil by single intrauterine
      administration: a novel method for contraception.
AB  - A novel use of neem (Azadirachta indica) oil, a traditional plant product, for
      long-term and reversible blocking of fertility after a single intrauterine
      application is described. Female Wistar rats of proven fertility were given a
      single dose (100 microliters) of neem oil by intrauterine route; control animals
      received the same volume of peanut oil. Whereas all control animals became
      pregnant and delivered normal litters, the rats treated with neem oil remained
      infertile for variable periods ranging from 107 to 180 days even after repeated
      matings with males of proven fertility. The block in fertility was, however,
      reversible as half of the animals regained fertility and delivered normal litters
      by five months after treatment, without any apparent teratogenic effects.
      Unilateral administration of neem oil in the uterus blocked pregnancy only on the
      side of application whereas the contralateral uterine horn treated with peanut
      oil had normally developing foetuses; no sign of implantation or foetal
      resorption was noted in the neem-oil-treated horn. The ovaries on both sides had
      4-6 corpora lutea indicating no effect of treatment on ovarian functions. The
      animals treated with neem oil showed a significant leukocytic infiltration in the
      uterine epithelium between days 3 and 5 post coitum, i.e. during the pre
      implantation period. Intrauterine application of neem oil appears to induce a pre
      implantation block in fertility; the possible mechanisms of the antifertility
      action are discussed.

PMID- 1983034
TI  - A polygenic model for the evolution and maintenance of conditional strategies.
AB  - We develop a genetic model for conditional strategies which places such
      strategies in the context of phenotypic plasticity. The model, which treats
      conditional strategies as polygenic threshold traits, indicates that, given
      requisite genetic variation in reaction norms, conditional strategies will evolve
      to their optimum level and be maintained by stabilizing selection, provided
      environmental variation results in a fitness trade-off for the alternative
      conditional phenotypes. The precise value for the evolutionary optimum is found
      to depend primarily on the probability density function of the environmental
      variation that influences the production of the conditional phenotypes and the
      magnitude of the fitness trade-offs of the conditional phenotypes across such
      environmental variation. The model is tested by application to three well-studied
      conditional strategies. In each case the predictions of the model are in good
      agreement with the results of these studies.

PMID- 1983035
TI  - Preferential expression of transient potassium current (IA) by 'short' hair cells
      of the chick's cochlea.
AB  - We have made a comparative study of the membrane properties of tall and short
      hair cells isolated from a selected region of the chick's cochlea. Tall hair
      cells are analogous to inner cochlear hair cells of mammals, and like those, are
      presynaptic to the majority of afferent neurons in the cochlea. Short hair cells,
      like mammalian outer hair cells, are the postsynaptic targets of efferent neurons
      that inhibit the cochlea. Voltage-clamp recordings have revealed that short hair
      cells have an inactivating potassium (K) current, IA, whereas tall hair cells
      have little or none. Short hair cells are also sensitive to the cholinergic
      agonist carbachol, whereas tall hair cells are not. This pattern is in accord
      with the selective distribution of efferent cholinergic synapses in the cochlea.
      Although IA is completely inactivated at the resting potential of the short hair
      cells, cholinergic agonists can hyperpolarize these cells by as much as 30 mV.
      This hyperpolarization removes inactivation and allows IA to modulate subsequent
      voltage-dependent processes in short hair cells. It is concluded that IA could
      increase the high frequency response of the hair cell by decreasing membrane
      resistance and thus the membrane time constant after inhibition. This will be of
      particular importance to cochlear function if short hair cells produce voltage
      dependent movements, as do mammalian outer hair cells.

PMID- 1983037
TI  - Active site complementation in engineered heterodimers of Escherichia coli
      glutathione reductase created in vivo.
AB  - By directed mutagenesis of the cloned Escherichia coli gor gene encoding the
      dimeric flavoprotein glutathione reductase, Cys-47 (a cysteine residue forming an
      essential charge-transfer complex with enzyme-bound FAD) was converted to serine
      (C47S) and His-439 (required to facilitate protonation of the reduced
      glutathione) was converted to glutamine (H439Q). Both mutant genes were placed in
      the same plasmid, pHD, where each of them came under the control of a strong tac
      promoter. This was designed to achieve equal over-expression of both genes in the
      same E. coli cell. The parental homo-dimers show no (C47S) or very little (H439Q)
      activity as glutathione reductases. The formation in vivo of heterodimers,
      carrying one crippled and one fully functional active site, was detected by
      absorbance spectroscopy and fluorescence emission spectrometry of enzyme-bound
      FAD and by active site complementation. The fractional distribution of homo- and
      hetero-dimers was in accord with that expected for a random association of enzyme
      subunits. In a homo-dimer, the H439Q mutation leads to a big fall in the value of
      Km for NADPH which binds some 1.8 nm from the point of mutation (Berry, A.,
      Scrutton, N.S. & Perham, R. N. Biochemistry 28, 1264-1269 (1989)). However, the
      one active site in the H439Q/C47S hetero-dimer exhibited kinetic parameters
      similar to those of the wild-type enzyme. Thus, the effect of the H439Q mutation
      must be retained within the active site that accommodates it and is not
      transmitted through the protein to the second active site across the subunit
      interface.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1983036
TI  - Polymorphism of the TRAP gene of Plasmodium falciparum.
AB  - Natural sequence variation of the thrombospondin related anonymous protein (TRAP)
      gene of Plasmodium falciparum has been investigated by DNA analysis following the
      polymerase chain reaction amplification, and this shows the gene to be highly
      polymorphic. The region containing the sequence motif Trp-Ser-Pro-Cys-Ser-Val-Thr
      Cys-Gly (WSPCSVTCG), common to TRAP, the circumsporozoite protein, properdin, and
      thrombospondin, was invariant. Elsewhere in the molecule, over 50 amino acid
      substitutions are described including the insertion of an in-frame, small
      variable tandemly repeating motif between amino acid residues 352 and 353. Only
      one silent mutation was observed. Most nucleotide changes that occur in the first
      two codon positions result in conservative amino acid changes. Restriction
      fragment length polymorphism (RFLP) analysis was used to examine inheritance of
      TRAP in a cross between the HB3 and 3D7 clones of P. falciparum. Out of nine
      progeny examined, four possessed the HB3 gene and five the 3D7 gene. The TRAP
      gene hybridized to chromosome 13. Previous work has shown that a subtelomeric
      region of chromosome 13 from the 3D7 parent (marked by the HRP-III gene) was
      favoured strongly in this cross. The TRAP gene, however, is over 1 Mb away from
      this subtelomeric region and exhibits no such linkage because of chromosome
      crossovers. Five geographically separate isolates shared the same TRAP sequence
      as well as the same variant of the Th2R/Th3R region from the circumsporozoite
      protein. The correlation between independent markers in these isolates suggests
      that they have a common provenance.

PMID- 1983038
TI  - Photoperiodic control of the termination of reproduction in Japanese quail
      (Coturnix coturnix japonica).
AB  - Typically, birds come into breeding in the spring as a response to long days, and
      end reproduction some weeks later by becoming refractory to those long days. The
      refractory state is subsequently dissipated by the short days of autumn and
      winter, so producing once again a bird that can respond to long days. Bird
      species differ in the extent to which refractoriness is developed; the present
      experiments took advantage of the relative, rather than the absolute,
      refractoriness in quail to measure quantitatively the dissipation process. Quail
      were made refractory by exposure to long days, then transferred to short days and
      at various times thereafter photostimulated with longer daylengths, the degree of
      photoresponsiveness being assessed by measuring changes in luteinizing hormone
      (LH) secretion or cloacal gland size or both. The most clearcut results came from
      using 13L:11D as the test stimulus to measure photoresponsiveness, and this
      indicated, in both intact and castrated quail, no response to 13L:11D after one
      week of short days, a minor response after two weeks, a strong response after
      three weeks and a full response after five weeks. Thus refractoriness appears to
      be dissipated gradually under short days, and not in an all-or-none fashion.
      Confirmation of this conclusion came from experiments in which refractory quail
      were moved to short days and after one or two weeks transferred to a range of
      long daylengths. After one week of short days no responses were obtained to
      13L:11D or 14L:10D and moderate responses only to 16L:8D, but after two weeks of
      short days the magnitudes of all the responses were increased.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1983039
TI  - Physical mapping of deletion breakpoints in patients with X-linked ichthyosis:
      evidence for clustering of distal and proximal breakpoints.
AB  - Previous studies have shown that approximately 80% of patients with X-linked
      ichthyosis have a total deletion of the steroid sulphatase (STS) locus which lies
      in Xp22.3-Xpter. We show by Southern analysis that a common core of sequences are
      absent in 78.6% of our cases, suggesting that the deletion breakpoints may be
      highly clustered. To characterize the region in more detail a long-range physical
      map of over 3 megabases (Mb) surrounding the STS locus was constructed using
      pulse-field gel electrophoresis. The map enabled the order of sequences tel-SI19
      GMGXY3-[STS,GMGXY19]-GMGX9-[dic56 ,SIII2]-cen and the localization of the
      deletion breakpoints to be established. In ten cases the pulse-field evidence
      supports the clustering of breakpoints and indicates a deletion size of 2 Mb in
      most patients. Five CpG islands have been positioned around the STS locus and may
      be associated with other loci in the region involved in mental retardation and
      Kallman's syndrome. The map will be instrumental in an attempt to isolate and
      characterize the deletion breakpoints and to access other genes located in the
      region.

PMID- 1983040
TI  - [Complex color and form production of an uncommon case].

PMID- 1983041
TI  - [Soldering bridges after porcelain blending].

PMID- 1983042
TI  - [A case of periarteritis nodosa affecting major arteries].

PMID- 1983043
TI  - [2 cases of periarteritis nodosa in twin brothers].

PMID- 1983044
TI  - [Prostaglandins in the pathogenesis of vascular lesions in patients with
      rheumatic diseases].
AB  - Using the radioimmunological method the authors studied the level of
      prostaglandins (PG) E and F2 alpha in 76 patients with rheumatic diseases (RD)
      including 34 with various forms of systemic vasculitis (SV), 30 with systemic
      lupus erythematosus (SLE) and 12 with systemic sclerodermia (SSD). The condition
      of the microcirculatory bed was assessed by the method of bulbar angioscopy. A
      relationship between PG and first of all the pressor series, and the nature of
      vascular lesions in patients with RD was established. Hyperproduction of PGE was
      revealed in patients with lupus nephritis and SV in whom diseases ran their
      course with involvement of the kidneys and the nervous system. The level of PGF2
      alpha correlated with the markedness of vascular disorders in patients with
      ischemic and vasospastic syndromes as well as with skin forms of vasculitis in
      SLE.

PMID- 1983046
TI  - Dengue and dengue hemorrhagic fever.

PMID- 1983045
TI  - Trimepranol increases a negative inotropic effect of MgNa2EDTA in rabbits in
      vivo.
AB  - The effect of a pre-treatment with the chelator MgNa2EDTA (0.5 mg.kg-1 i.v.) on
      the influencing of cardiac contractility by Trimepranol (0.3 mg.kg-1 i.v.) was
      studied in rabbits in vivo under pentobarbital anaesthesia in the conditions of
      the spontaneous and paced heart rates and compared with the effects of the
      administration of the chelator MgNa2EDTA (0.5 mg.kg-1 i.v.) alone. The
      administration of the chelator alone induced especially commencing with the end
      of the first hour of observation, a progressive decrease in the left ventricular
      dP/dtmax. both in the paced heart (max. 67.0 % in the 170th min) and in the
      nonpaced heart conditions (max. 60.9 % in the 180th min). The administration of
      Trimepranol (120 min after the pre-treatment with the chelator) resulted in a
      pronounced increase in a negative inotropic effect (max. 43.1% in the paced and
      35.3 % in the non-paced heart, always in the 130th min, i.e., 10 min after the
      administration of the beta-blocker), which was in most intervals significantly
      different from the values of dP/dtmax. after the administration of the chelator
      alone. A significant increase in the negative inotropic effect was manifested
      also by deaths of a number of experimental animals before the end of observation.
      On the basis of the results obtained, it is possible to assume that the
      combination of the administration of MgNa2EDTA with beta-blockers may especially
      result in an increase in the cardiodepressive action and in an occurrence of
      adverse effects on the hemodynamics of the organism.

PMID- 1983047
TI  - Nutrition and nation building.

PMID- 1983048
TI  - International symposium on dengue and dengue hemorrhagic fever. Introduction.

PMID- 1983049
TI  - Human immune responses to dengue viruses.
AB  - Dengue fever (DF) and dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS)
      are major public health problems in many areas of the world. We are analyzing the
      human immune responses to dengue viruses, in order to understand the mechanism of
      recovery from dengue virus infections and the pathogenesis of DHF/DSS. Human
      natural killer (NK) cells lyse dengue virus-infected cells to a greater degree
      than uninfected cells. Antibodies to dengue viruses augment the lysis of dengue
      virus-infected cells by NK cells. Dengue virus-infected monocytes produce high
      levels of interferon alpha (IFN alpha). DR+ lymphocytes also produce high levels
      of IFN alpha after contact with dengue virus-infected monocytes. The IFN alpha
      produced protects uninfected monocytes from dengue virus infection. These results
      suggest that NK cells and IFN alpha may play an important role in controlling
      primary dengue virus infection. Dengue virus-specific CD4+CD8(-)T lymphocytes and
      CD4(-)CD8+T lymphocytes are present in the peripheral blood mononuclear cell
      population from donors who were infected with dengue virus. Most of CD4+T
      lymphocytes are dengue serotype-crossreactive. They lyse dengue virus-infected
      autologous cells in an HLA class II-restricted fashion, and produce interferon
      gamma (IFN gamma). IFN gamma augments dengue virus infection of monocytic cells
      in the presence of antidengue virus antibodies by increasing the number of Fc
      gamma receptors. Dengue virus-specific CD8+T lymphocytes lyse dengue virus
      infected autologous cells in an HLA class I-restricted fashion. These CD8+T
      lymphocytes are also dengue serotype-crossreactive.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1983050
TI  - [Beta-adrenoblockaders and calcium antagonists in the treatment of patients with
      ischemic heart disease combined with hypertension].
AB  - The authors studied 67 patients with ischemic heart disease associated with
      hypertensive disease and revealed that the use of beta-adrenoblockaders and
      calcium antagonists resulted in a reduction of the manifestations of the disease,
      increase of physical load tolerance, optimization of its hemodynamic and oxygen
      provision. In patients under 60 years of age of beta-adrenoblockaders resulted in
      an increase of the myocardial contractility. This was not observed in those over
      60 years of age. It is concluded that in patients combining IHD with hypertensive
      disease under 60 it is more preferable to use beta-adrenoblockers, in those over
      60--calcium antagonists.

PMID- 1983051
TI  - [Thyroid-stimulating immunoglobulins and the incidence of postoperative
      hypothyroidism in patients with diffuse toxic goiter].
AB  - Thyroid function was studied in 38 patients with diffuse thyroid goiter after
      subtotal thyroidectomy (3.82 and 25.9 months after surgery. Postoperative
      hypothyroidism developed less frequently in diffuse goiter patients who showed
      before treatment thyro-stimulating antibodies in the blood. The authors recommend
      a differential approach to the volume of thyroidectomy depending on the presence
      and absence of thyroid-stimulating antibodies before the operation.

PMID- 1983052
TI  - [Our first experience with allogeneic and autologous transplantation of
      hematopoietic stem cells].
AB  - The main problems and difficulties in transplantation of haematogenous stem cells
      are discussed. The problems include: organization of a team of specialists and
      bone marrow transplantation centre, preparation of the recipient (patient)
      complications connected with preparation for transplantation, graft taking, graft
      versus host disease, recurrence of the underlying disease. In the analysis only
      those patients (8 cases) are included who had received marrow transplantation
      after chemotherapeutic-radiotherapeutic preparation (3 patients are alive). The
      first experiences are described also with three autotransplantations of
      haematogenous stem cells obtained by means of cell separator from peripheral
      blood. These experiences indicate that it is possible in our country to carry out
      this highly sophisticated method which requires, however, further improvements
      and ensuring of adequate personnel and equipment.

PMID- 1983053
TI  - Adrenaline in cardiovascular diseases--effect of beta-adrenoceptor antagonists.
AB  - By subcutaneous insertion of osmotic minipumps leading to continuous infusion of
      l-adrenaline, we were able to induce hypertension in normotensive Wistar-Kyoto
      strain (WKY) rats which was shown to be completely reversible by application of
      the non-selective beta-adrenoceptor antagonist carvedilol. No consistent effect
      of adrenaline on heart rate could be observed. At least in rat heart, adrenaline
      replaced the original neurotransmitter noradrenaline in amine storage sites, the
      sum of all catecholamines remaining unchanged. By comparing tissue concentrations
      of endogenous amines of spontaneously hypertensive rats (SHR) and stroke-prone
      SHR (SHR-SP) to the corresponding levels of their normotensive controls of the
      Wistar-Kyoto strain, we detected various differences in amine handling during the
      development of high blood pressure. Significant increases of adrenal gland
      catecholamines at the ages of 8 and 14 weeks are accompanied by striking
      alterations of catecholamine (CA) storage in other peripheral organs like the
      heart and kidneys. Most prominent increases, as compared to controls, were found
      in adrenaline concentrations in heart and kidney at all ages studied, with levels
      two to four times higher than the respective WKY concentrations. The results are
      compatible with a permissive role of adrenaline as a cotransmitter in the
      initiation and/or maintenance of hypertension. After incorporation into
      endogenous amine storage vesicles, e.g., of the heart, adrenaline is probably
      released, together with noradrenaline, upon nerve stimulation. By stimulating
      presynaptic beta 2-adrenoceptors, adrenaline is able to facilitate noradrenaline
      release and to enhance noradrenergic vasoconstriction. The resulting increase of
      peripheral sympathetic tone may be responsible for the pathogenesis of rat
      genetic and human essential hypertension, as well as for the triggering of
      myocardial infarction. The blockade of presynaptic beta-receptors is supposed to
      represent an important mechanism of action of non-selective beta-blocking agents.
      In the case of carvedilol, this effect is supported by additional antagonism at
      vascular alpha-adrenoceptors, leading to vasodilation.

PMID- 1983055
TI  - Pharmacological and clinical aspects of drug therapy in coronary heart disease:
      clinical aspects of therapy with beta-adrenoceptor antagonists.
AB  - beta-adrenergic blocking drugs reduce myocardial oxygen consumption, chiefly by
      reducing heart rate as the principal basis for their efficacy in ischaemic heart
      disease. Regardless of the presence of associated properties, beta, selectivity,
      partial agonist activity, all beta-blocking drugs have been found efficacious in
      the treatment of angina pectoris, both alone and in combination with drugs such
      as nitrates and calcium antagonists. Holter monitoring has demonstrated beta
      blockers also reduce the incidence of silent ischaemia. Finally, they are
      established in the treatment of acute infarction and secondary prevention of
      recurrences. There are inherent disadvantages of inhibition of the beta
      sympathetic, most notably the precipitation of asthma and heart failure in
      susceptible subjects. Recently, combined-action beta-blocking drugs have been
      developed, i.e. combining beta blockade with peripheral vasodilator activity,
      either by alpha 1, blockade, beta 2 stimulation or a direct effect independent of
      either receptor. They have a more favourable haemodynamic profile and, while
      initial studies are promising, it is not yet clear whether this will be
      translated into improved clinical benefit in ischaemic heart disease.

PMID- 1983054
TI  - Experimental and clinical pharmacology of carvedilol and other drugs combining
      vasodilation and beta-adrenoceptor antagonism in a single molecule.
AB  - Combinations of beta-adrenoreceptor blocking agents and vasodilators have been
      widely used because of their favorable hemodynamic actions and their high
      efficacy. In comparison with the free combination of the two active principles,
      substances that combine vasodilation and beta-blockade in a single molecule may
      lead to a simplification of therapy and thus to an improvement in compliance.
      Substances that show clear beta-blocking and vasodilating actions at therapeutic
      doses have already been introduced to therapy or are in an advanced stage of
      clinical development. The vasodilating action of amosulalol, carvedilol and
      labetalol is achieved by blockade of the alpha 1-receptors. In contrast, partial
      agonistic action on beta 2-receptors is responsible for the vasodilatation with
      dilevalol. This mechanism probably also plays an important role in the
      vasodilatation induced by celiprolol. While classical beta-blocker lead to a rise
      in peripheral resistance and to a marked fall in cardiac output, peripheral
      resistance falls during treatment with vasodilating beta-blockers. The cardiac
      output is either only slightly reduced or virtually unchanged. Surprisingly,
      three months' treatment with the vasodilating beta-blocker bucindolol in patients
      with severe heart failure led to a rise in cardiac output and in ejection
      fraction and to a reduction of the heart rate and pulmonary wedge pressure. An
      improvement of left-ventricular function was also obtained on administration of
      carvedilol in patients with coronary heart disease. Theoretically, it is
      conceivable that substances with additional alpha 1-blocking actions, such as
      labetalol, carvediolol or amosulalol, or with partial agonistic activity such as
      celiprolol or dilevalol, would have a clearly more favourable effect on the blood
      lipid profile than the classical beta-blocking agents. Initial results appear to
      confirm this, but final conclusions will only be possible when the results of
      prospective comparative studies are available.

PMID- 1983056
TI  - [Subdural empyema].
AB  - The subdural empyema is a severe inflammatory cerebral affection and shows some
      diagnostic and therapeutic problems. Extracerebral infections especially in the
      rhinogenous and otogenic region represent the most frequent cause of the subdural
      empyema. Seven cases, treated between 1982 and 1986 in our department, are the
      base to discuss the problems of symptomatology, differential diagnosis and
      therapy. The treatment of choice is a sudden craniotomy in combination with a
      through-drainage and administration of antibiotics.

PMID- 1983057
TI  - [Is the term "sapronoses" needed?].

PMID- 1983058
TI  - [The synthesis and biological activity of substituted tetrahydroisoquinoline
      compounds].
AB  - Tetrandrine possesses calcium antagonistic and hypotensive effects. It was
      cleaved into two compounds O-methylcoclaurine (I) and N-methylarmepavine (II) by
      Na/NH3. Pharmacological test indicated that I and II showed weaker calcium
      antagonistic activity but having alpha-adrenoceptor antagonistic effect. With I
      and II as lead compounds as well as integration of some structural feature of
      calcium antagonists and SAR of antiarrhythmic drugs, two kinds of substituted
      tetrahydroisoquinoline derivatives III, IV were designed and synthesized in order
      to search for novel cardiovascular drugs. Tetrahydroisoquinoline compounds were
      first synthesized by the Bischler-Napiraski cyclization with substituted
      phenethylamine and aromatic acetic acid or substituted cinnamic acid as starting
      materials. N-alkylsubstituted tetrahydroisoquinoline compounds were prepared by
      the reaction of 4 with alkyl halide to produce 5, then reduction of 5 by KBH4 to
      give III13-25. The synthesis of N-alkylaminoethyl substituted
      tetrahydroisoquinoline compounds involved the reaction of 6 with chloroacetyl
      chloride to obtain IV1-3, the reaction of IV1-3 with secondary amine to produce
      9, and then reduction of 9 with LiA1H4 to give IV16-19. Preliminary tests showed
      that most of these compounds exhibited varied degree of alpha-adrenoceptor
      antagonistic effect, and some of them possess calcium antagonistic activity. In
      anesthetic normal rats III15, 19 showed certain degree of hypotensive effect.
      IV10, 11 exhibited significant protective effect on experimental arrhythmic
      animals. The results of quantum chemical calculation of some compounds
      demonstrate that the compounds might act with alpha 1-adrenoceptor by forming
      charge-transfer complex.

PMID- 1983059
TI  - [Synthesis of 3-[4-[(3-alkylamino-2-hydroxy)propoxy]phenyl (benzyl)]-substituted
      4(3H)-quinazolines as antimyocardial ischemic agents].
AB  - In order to search for effective antimyocardial ischemic agents, fourteen new 3
      [4-[(3-alkylamino-2-hydroxy)propoxy]phenyl(benzyl)]-substituted 4(3H)
      quinazolinones (II) were synthesized. Substituted o-aminobenzoic acids used as
      the starting materials were allowed to react with acetic anhydride and then p
      amino-phenol (method A), or with N-(4-hydroxyphenyl)formamide (method B), or with
      thionyl chloride and then N-(4-hydroxybenzyl)formamide (method C) to form 3-[(4
      hydroxyphenyl(benzyl)]-substituted 4(3H)-quinazolinones (III). The intermediate
      III reacted with epichlorohydrin to form the epoxides (IV). The reaction of IV
      with an excess of isopropylamine or tert-butylamine in boiling chloroform gave
      the desired products. Of all the compounds synthesized, compounds II3-5 and II13
      were found to increase the tolerance of mice to hypoxia. Further evaluation is in
      progress.

PMID- 1983060
TI  - Immunomodulation by histamine.
AB  - Blood histamine proved to be important for the immune homeostasis. By its direct
      action or by means of H-2 receptors it end or prevents the excessive immune
      response. Recent studies revealed changes in cell mediated immunity in subjects
      with atopia, with increased histaminemia and their obvious protection against
      cancer. In patients with cancer, hypogammaglobulinemia, AIDS, the depression of
      the immune responses was partly accounted for by the decrease of blood histamine
      and by the change of the number of H-2 receptors. Hence the attempt to treat
      these diseases with H-2 antagonists associated or not with histamine.

PMID- 1983061
TI  - [Nonspecific Onishi-Takayasu arteritis. Experience at the I. Chavez National
      Institute of Cardiology].

PMID- 1983062
TI  - [The use of beta-blockers in pregnancy].

PMID- 1983063
TI  - Effects of chronic administration of mergocryptine on changes in neurotransmitter
      levels in the ischemic gerbil brain.
AB  - Changes in various neurotransmitter systems of the gerbil brain during ischemia
      and the effects of administration of mergocryptine, a new ergot derivative, were
      studied. Gerbils intraperitoneally administered 0.5 mg/kg of mergocryptine or the
      vehicle once a day for 14 days were used. The administration of mergocryptine to
      control animals had no effect on the contents of neurotransmitters or their
      metabolites in various regions of the brain, but it corrected abnormalities in
      the neurotransmitter systems caused by ischemia. These results suggest the
      usefulness of mergocryptine against the deleterious effects of brain ischemia.

PMID- 1983064
TI  - Pharmacological responses to dopamine in isolated guinea-pig cardiovascular
      tissues: mechanisms of action.
AB  - The mechanisms responsible for the positive inotropic, positive chronotropic and
      vasoconstrictor responses to dopamine in isolated guinea-pig cardiovascular
      tissues have been investigated in the present study. Since dopamine is the
      immediate precursor of noradrenaline, the role of noradrenaline in the
      pharmacological responses after addition of dopamine has been assessed. In
      isolated, contracting right ventricular papillary muscles, dopamine-induced
      positive inotropy (-log EC50, 4.77 +/- 0.06) was unaltered by incubation with
      dopamine antagonists (SCH 23390, domperidone), alpha-adrenoceptor antagonists
      (prazosin, yohimbine), or an inhibitor of uptake1 (cocaine). Practolol (selective
      beta 1-adrenoceptor antagonist) and ICI 118,551 (selective beta 2-adrenoceptor
      antagonist) were noncompetitive antagonists to dopamine. Block of vesicular
      uptake by reserpine antagonized the positive inotropic responses to dopamine (
      log EC50, 4.03 +/- 0.05) but not to noradrenaline; these responses were
      antagonized by both practolol and ICI 118,551. Chemical sympathectomy by 6
      hydroxydopamine antagonized the responses to dopamine (-log EC50, 3.76 +/- 0.11)
      but potentiated the responses to noradrenaline (-log EC50, 7.35 +/- 0.07).
      Inhibition of monoamine oxidase with pargyline potentiated the responses to
      dopamine (-log EC50, 6.05 +/- 0.04) and noradrenaline; the potentiation of
      dopamine responses was unaffected by chemical sympathectomy. Inhibition of
      dopamine beta-hydroxylase with sodium diethyldithiocarbamate antagonized the
      inotropic responses to dopamine (-log EC50, 4.36 +/- 0.05) but not to
      noradrenaline. Similar results were obtained in guinea-pig left atria (positive
      inotropy) and right atria (positive chronotropy), except that chemical
      sympathectomy failed to affect the chronotropic responses. In thoracic aortic
      rings, dopamine contracted vascular smooth muscle by direct partial agonism of
      alpha 1-adrenoceptors, without involvement of dopamine beta-hydroxylase. Thus,
      there is antagonism of the cardiac, but not the vascular responses to dopamine by
      inhibition of dopamine beta-hydroxylase. This shows that the conversion of
      dopamine to noradrenaline is important in the inotropic and chronotropic
      responses, but not the vascular responses to dopamine.

PMID- 1983066
TI  - Characterization of the inhibitory 5-HT receptor in the rat vas deferens.
AB  - The inhibitory effects of 5-HT on the response of the rat isolated rat vas
      deferens preparation to electrical stimulation (0.1 Hz) has been investigated. A
      number of compounds, previously shown to possess antagonist activity at the rat
      central nervous system 5-HT autoreceptor, including methiothepin and the beta
      blockers propranolol, alprenolol and cyanopindolol, have been found to possess
      virtually identical activity in the rat vas deferens. Cyanopindolol (Ke versus 5
      HT = 4.9 nM) was the most potent antagonist tested, but was even more effective
      as a beta 2-antagonist (Ke = 0.14 nM) in this preparation. Prizidilol (Ke versus
      5-HT = 30.2 nM, Ke versus isoprenaline = 75 nM) and acebutolol (Ke versus 5-HT =
      297 nM, Ke versus isoprenaline = 3300 nM) have been identified as beta-blocking
      compounds that possess higher activity at the 5-HT receptor than at the beta 2
      receptor. Several compounds, previously shown to possess 5-HT agonist activity,
      have been tested in this preparation and their potencies relative to 5-HT were as
      follows: 5-carboxyamidotryptamine (x 7), TFMPP (x 0.1) and LSD (x 0.04). RU24969
      was found to behave as a low intrinsic activity partial agonist. All the evidence
      is consistent with the inhibitory 5-HT receptor present in this preparation being
      identical to the 5-HT autoreceptor found in the rat central nervous system which
      has been identified as the receptor with which the 5-HT1B binding site is
      associated.

PMID- 1983065
TI  - Vasoconstrictor responses to the alpha 2-adrenoceptor agonist UK14304 during
      responses to noradrenaline, phenylephrine, serotonin and vasopressin of the rat
      tail artery.
AB  - In the isolated perfused rat tail artery, the alpha 2-adrenoceptor agonist
      UK14304 alone did not exert a direct vasoconstrictor action until a concentration
      of at least 30 microM was reached. However, when administered during the
      sustained vasoconstrictor response to 1.6 microM vasopressin, UK14304 (1-100 nM)
      produced additional concentration-dependent increases in perfusion pressure. The
      vasoconstrictor response to UK14304 in the presence of vasopressin was
      antagonized by idazoxan (1 microM) but was not affected by prazosin (10 nM),
      indicating that it was due to activation of alpha 2-adrenoceptors, and it was
      reduced by diltiazem (10 microM) and abolished when perfusion was done with a
      Ca2(+)-free solution, suggesting that the effect depends on the influx of Ca2+.
      UK14304 (50 nM) also produced a further increase in perfusion pressure when given
      during sustained vasoconstrictor responses to phenylephrine (1 microM) or low
      concentrations (100 nM) of noradrenaline or serotonin. However, UK14304 did not
      produce a further increase in perfusion pressure when given during sustained
      vasoconstrictor responses to higher concentrations (300 nM) of noradrenaline or
      serotonin: the lack of an additional effect of UK14304 was not due to the primary
      response to noradrenaline or serotonin being maximal. The findings show that
      vasoconstrictor responses following activation of alpha 2-adrenoceptors may be
      uncovered by an increase in vascular tone produced by some agonists.

PMID- 1983068
TI  - Kinetics of the inhibition of hog kidney D-amino acid oxidase by short-, medium-
      and long-chain fatty acids.
AB  - Various fatty acids were studied in vitro as inhibitors of pure hog kidney D
      amino acid oxidase by means of a spectrophotometric peroxidase-coupling method
      using D-methionine as a substrate. All the fatty acids tested behaved as
      substrate-competitive inhibitors of the enzyme. The affinity of the saturated
      aliphatic acids for D-amino acid oxidase decreased from pentanoate (5:0; Ki = 220
      microM) to laurate (12:0; Ki = 675 microM), then rose to a maximum with stearate
      (18:0; Ki = 36 microM), suggesting the presence of a site in the active center of
      the enzyme that accepts long-chain fatty acid alkyl groups. Unsaturation did not
      further increase the affinity of the fatty acid for this binding site.

PMID- 1983067
TI  - Methoxyphenamine inhibits histamine-induced bronchoconstriction in anaesthetized
      guinea-pigs and histamine-induced contractions of guinea-pig ileum in vitro.
AB  - Measurements were made of the effects of methoxyphenamine hydrochloride on
      histamine-, acetylcholine- and U46619-induced bronchoconstriction in
      pentobarbitone-anaesthetized guinea-pigs, and on histamine- and acetylcholine
      induced contractions of guinea-pig ileum in vitro. Methoxyphenamine (20 mg/kg,
      i.v.) did not affect bronchoconstriction induced by acetylcholine or the
      thromboxane A2-mimetic U46619. However, it produced a parallel rightward shift
      [2.94-(1.79, 4.41) fold, 95% confidence limits in parentheses] of the curve
      relating bronchoconstrictor responses to log-dose of histamine at a total dose of
      13 mg/kg, i.v., which was not significantly different from the shift [3.30-(1.93,
      5.56) fold] produced by 3 micrograms/kg, i.v., of the histamine antagonist
      mepyramine maleate. Histamine-induced contractions of the isolated guinea-pig
      ileum were antagonized by methoxyphenamine (10(-5) to 10(-3) M). The histamine
      log-concentration-response curve was shifted to the right in a parallel manner by
      methoxyphenamine (10(-5) to 10(-4) M), without depression of maximum responses.
      However, at higher concentrations, maximum responses were reduced. The slope of
      the Schild plot was significantly different from -1. The degree of the rightward
      shift of the concentration-response curves to histamine, produced by 10(-5) M of
      methoxyphenamine [3.90-(2.83, 4.97) fold], was not significantly different from
      that produced by 3 x 10(-9) M of mepyramine [4.60-(2.86, 6.52) fold].
      Methoxyphenamine, at concentrations of 10(-5) to 3 x 10(-4) M, had no significant
      effect on responses of guinea-pig ilea to acetylcholine (10(-9) to 10(-5) M).
      These results indicate that methoxyphenamine antagonizes the effects of histamine
      both in vivo and in vitro. In vitro studies indicate a noncompetitive antagonism.

PMID- 1983069
TI  - The effect of dopamine D1 and D2 receptor agonists on inositol phosphate turnover
      in rat striatal slices.
AB  - There is a lot of controversy in the literature about the role of dopamine D1 and
      D2 receptor stimulation on the turnover of phosphoinositols, and phosphoinositols
      are one of the important second messenger. In order to resolve this controversy,
      the effect of dopamine receptor stimulation on turnover of phosphoinositols was
      studied by estimation of the accumulation of individual labelled inositols in rat
      striatal slices which were prelabelled with [3H]myoinositol. Incubation of the
      prelabelled striatal slices with 1 microM of quinpirole, D2 specific agonist or
      with 1 microM of SKF-38393, D1 specific agonist, did not affect the accumulation
      of basal level of either inositol monophosphate, or inositol biphosphate, or
      inositol triphosphate. In addition, in conclusion of D1 specific antagonist cis
      flupentixol or D2 specific antagonist sulpiride did not affect the basal levels
      of inositol phosphates. The activity of enzyme phospholipase-C which produces
      these inositol phosphates was also measured in rat striatal membrane. Incubation
      of rat striatal membrane with either agonist quinpirole or SKF-38393 did not
      change the basal level of phospholipase C. Our data thus indicate that occupation
      of dopamine receptors did not affect the inositol phosphate system in rat
      striatum.

PMID- 1983071
TI  - Immunological study of condylomata acuminata in men infected with the human
      immunodeficiency virus.
AB  - As condylomata acuminata often persist in individuals infected with the human
      immunodeficiency virus (HIV), an immunohistological study of warts from infected
      men was undertaken to further knowledge about human papillomavirus persistence in
      this group. Using an indirect immunoperoxidase method and a panel of monoclonal
      antibodies, the phenotypes of cells were studied in cryostat sections of perianal
      or anal warts removed from 14 HIV-infected men (10 homosexual and 4 heterosexual)
      and from 16 non-infected men (10 homosexual and 6 heterosexual). Although the
      median numbers of CD1+, CD3+ and CD4+ cells per unit area were similar in each
      group of individuals, the number of CD8+ cells was significantly higher in HIV
      infected homosexual men when compared with non-infected individuals and HIV
      infected heterosexual men. The median CD4+ cell count in the peripheral blood was
      significantly higher in HIV-infected heterosexual men than in HIV-infected
      homosexual men (P less than 0.05). These findings may reflect differences in
      duration of HIV infection between the two groups. There was no significant
      difference in the proportion of cells expressing interleukin-2 receptors between
      HIV-infected and non-infected individuals. Natural killer (CD16+) cells were not
      identified in any of the condylomata.

PMID- 1983070
TI  - Regulation of IL-4 lymphokine gene expression and cellular proliferation in
      murine T helper type II cells.
AB  - Activation of T cells results in the production of lymphokines and cellular
      proliferation. Protein kinase C (PKC) plays a key role in this process. It has
      been shown that this enzyme is essential to elicit a response to Con A or
      specific antigen in CD4+ T helper type 1 (Th 1) cells that secrete IL-2. We have
      now explored the signal transduction pathway that leads to transcription of the
      IL-4 gene and proliferation in murine CD4+ T helper type 2 (Th 2) cells.
      Surprisingly, we have found in two independently derived Th 2 clones that neither
      cellular proliferation nor IL-4 lymphokine production is affected by blocking or
      depletion of PKC. This differential mechanism of signal transmission leading to
      cellular activation implies a new distinction between murine Th 1 and Th 2 cells.

PMID- 1983072
TI  - Cll-matrix contacts and pericellular proteolysis. Proceedings of the 13th Sigrid
      Juselius Symposium. Helsinki, 12-15 August 1990.

PMID- 1983073
TI  - The pivotal role of the Leu-CAM and ICAM molecules in human leukocyte adhesion.
AB  - Cellular adhesion is of fundamental importance in leukocyte physiology. It is a
      complex, strictly regulated process, which involves the participation of several
      cell surface glycoproteins. Among the most important are the Leu-CAMs or the
      CD11/CD18 integrin receptors, and their adhesion ligands ICAM-1 (CD54) and ICAM
      2. In this review we summarize some recent work on various aspects of these
      molecules.

PMID- 1983075
TI  - [Epidemiological survey of epidemic haemorrhagic fever in Xianning County].
AB  - The incidence, distribution pattern and trend of disease spreading of EHF in
      Xianning Country, Hubei province during 1971-1985 are described. Serologic study
      showed that the serum antigen positivity rate was 12.90% for Apodemus Agragrius
      and 6.67% for Rattus Norvegicus and that the serum antibody positivity rate was
      61.54% in FHF patients and 30.85% in the exposed contacts of the patients'
      families in the epidemic area. In 1985, the HFRS virus A24 was isolated from
      Apodemus Agragrius and identified.

PMID- 1983076
TI  - [A ten-year retrospective investigation of serum against EHF antibodies in
      Nanchong District, Sichuan].
AB  - This paper reports a retrospective inquiry of blood serum against epidemic
      hemorrhagic fever (EHF) antibodies in some of our hospital treated EHF patients
      during 1974-1984. It was found that the total positive rate of sera against EHF
      antibodies obtained from different periods of EHF patients was 86.8% (170/196).
      The titers were highest in patients who had been attacked within one year and the
      titers markedly decreased from the second year onwards. However certain level of
      serum titre could be detected up to 8th-10th year after the acute infection.
      Normal persons in high-incidence districts and medical workers who had kept in
      close contact for many years with EHF patients were found to be negative. It is
      presumed that this disease's latent infection is probably very low.

PMID- 1983074
TI  - The expression and interactions of laminin in the developing nervous system.

PMID- 1983077
TI  - Induction of eczematous skin reaction in experimentally induced hyperplastic skin
      of Balb/C mice by monoclonal anti-DNP IgE antibody: possible implications for
      skin lesion formation in atopic dermatitis.
AB  - Biphasic skin reaction with peak response at 1 and 24 h with prominent mast cell
      degranulation was induced by intravenous application of a monoclonal anti-DNP IgE
      antibody and subsequent skin test. This reaction was hapten-specific and mast
      cell-dependent because no reaction was observed when oxasolone was used as an
      elicitation antigen or skin test was elicited in genetically mast-cell-deficient
      mice (W/Wvv). A partial spongiotic reaction and mononuclear cell infiltration
      into the epidermis were observed in mice with hyperplastic epidermis induced by
      topical retinoic acid. Cotransfer of DNFB-sensitized lymph node cells with anti
      DNP IgE antibodies failed to enhance the skin test reaction in unsensitized mice.
      These results suggest that, to some degree, IgE antibody may play some role in
      the development of eczematous skin lesions in the rodent system without the
      involvement of cellular hypersensitivity.

PMID- 1983078
TI  - Antiepileptic drugs, hepatic enzyme induction and raised serum alkaline
      phosphatase isoenzymes.
AB  - Thirteen patients with epilepsy on long-term antiepileptic drug therapy and who
      had a persistently raised serum alkaline phosphatase (ALP) activity were
      investigated biochemically. Twelve patients had a raised liver ALP-isoenzyme
      activity and in nine of these the bone ALP-isoenzyme activity was normal. Gamma
      glutamyl transferase (gamma GT) levels were raised in 12 patients. Two patients
      were hypoglycaemic. One patient fitted the biochemical parameters for subclinical
      osteomalacia. The resultant clinical picture showed 75% of patients with
      borderline hypocalcaemia, raised liver ALP, raised gamma GT and normal bone ALP
      activities in whom 1,25 dihydroxy-cholecalciferol (1,25-DHCC; vitamin D) therapy
      would be inappropriate, whilst 1,25-DHCC therapy might be considered for those
      with borderline hypocalcaemia and a raised bone ALP activity (three patients). No
      evidence was found of hepatotoxicity or drug induced cholestasis. It is
      considered that the induction of liver microsomal enzymes by antiepileptic drugs
      could include liver ALP (as opposed to bone ALP) as well as gamma GT and the
      inactivation pathways for 1,25 DHCC.

PMID- 1983080
TI  - Autologous bone marrow or blood stem cell transplantation in chronic myeloid
      leukemia. France Auto Greffe Group.
AB  - Forty-seven patients with Ph1-positive chronic myeloid leukemia in transformation
      (CML) underwent autologous transplantation of peripheral blood stem cells (ABSCT)
      collected at the original diagnosis before any treatment. They were treated
      according to 3 consecutive strategies: single transplant (Group I = 17 patients),
      double transplant (Group II = 13 patients), double transplant followed by
      recombinant alpha interferon (IFN) (Group III = 17 patients). The actuarial
      median duration of second chronic phase was 3 months, 10 months and 18 months for
      Group I, Group II and Group III patients (p less than 0.0001). The encouraging
      results observed for Group III patients prompted us to propose ABSCT for patients
      in chronic phase with initial prognostic factors (high-risk CML) suggesting that
      IFN will not be effective if administered as front-line therapy. To date, 13
      patients with high-risk CML underwent ABSCT followed by IFN therapy. Ten patients
      achieved a complete hematological response following transplantation. Two of 6
      evaluable patients had a cytogenetical response 6 months after ABSCT. A longer
      follow-up is needed to see if the duration of chronic phase may be prolonged.

PMID- 1983079
TI  - Complete genetic organization and functional aspects of the Escherichia coli S
      fimbrial adhesion determinant: nucleotide sequence of the genes sfa B, C, D, E,
      F.
AB  - The S fimbrial adhesin (sfa) determinant of E. coli comprises nine genes situated
      on a stretch of 7.9 kilobases (kb) DNA. Here the nucleotide sequence of the genes
      sfa B and sfa C situated proximal to the main structural gene sfaA is described.
      Sfa-LacZ fusions show that the two genes are transcribed in opposite directions.
      The isolation of mutants in the proximal region of the sfa gene cluster, the
      construction of sfa-phoA gene fusions and subsequent transcomplementation studies
      indicated that the genes sfa B and sfa C play a role in regulation of the sfa
      determinant. In addition the nucleotide sequence of the genes sfa D, sfa E and
      sfa F situated between the genes sfa A and sfa G responsible for S subunit
      proteins, were determined. It is suggested that these genes are involved in
      transport and assembly of fimbrial subunits. Thus the entire genetic organization
      of the sfa determinant is presented and compared with the gene clusters coding
      for P fimbriae (pap), F1C fimbriae (foc) and type I fimbriae (fim). The
      evolutionary relationship of fimbrial adhesion determinants is discussed.

PMID- 1983081
TI  - Immunohistochemical detection of multidrug resistance associated P-glycoprotein
      in stromal cells of malignant lymphomas.
AB  - We examined the distribution of the P-glycoprotein by immunohistochemistry in 25
      malignant lymphomas (15 CHOP-derived regimen resistant non-Hodgkin's lymphomas
      and 10 Hodgkin's diseases). The study was performed on both cryostat and ModAMeX
      sections; the latter method preserves fixation-sensitive antigens and allows a
      more precise morphologic identification of neoplastic and non-neoplastic cell
      populations in contrast to cryostat sections. In both non-Hodgkin's lymphomas and
      Hodgkin's diseases, cells that were stained on cryostat sections were identified
      as macrophages and endothelial cells and not neoplastic lymphoid cells, by the
      ModAMeX technique. These findings suggest that the quantitative assessment of the
      multidrug resistance gene RNA by Northern blotting performed on fresh homogenates
      may overestimate the RNA content of neoplastic cells in a number of lymphoid
      tumors. In addition, the mechanism of chemoresistance in non-Hodgin's lymphomas
      is less likely to be associated with the P-glycoprotein expression.

PMID- 1983083
TI  - [VIIth French International Congress of Leprosy. 3-6 February 1991, Bamako, Mali.
      Abstracts].

PMID- 1983082
TI  - Coexistent multiple myeloma and MEN type 1.

PMID- 1983084
TI  - Immobilization of Norwegian reindeer (Rangifer tarandus tarandus) and Svalbard
      Reindeer (R. t. platyrhynchus) with medetomidine and medetomidine-ketamine and
      reversal of immobilization with atipamezole.
AB  - The sedative action of medetomidine (-ketamine) was studied in 12 captive
      Norwegian semidomesticated reindeer (NR), including 4 newborn calves, and in 7
      free-living Svalbard reindeer (SR). Medetomidine, with or without ketamine,
      caused effective, reliable immobilization in NR. Doses of 50-200 micrograms/kg
      medetomidine alone or 30-125 micrograms/kg medetomidine combined with greater
      than or equal to 300 micrograms/kg ketamine induced complete immobilization, good
      muscle relaxation and persistent, deep sedation with little respiratory
      depression in NR; SR required higher doses. Atipamezole successfully antagonized
      medetomidine (-ketamine) resulting in rapid and persistent reversal of
      immobilization in all cases (NR and SR). Both medetomidine and atipamezole had
      wide safety margins and no conspicuous lasting side effects after reversal.

PMID- 1983085
TI  - [Vulvovaginal and cervix uteri involvement disclosing pemphigus vulgaris.
      Efficacy of gold salt therapy].

PMID- 1983086
TI  - Monoamine neurotransmitter receptors: ligand-receptor models.
AB  - Recent medicinal chemistry studies have led to the idea that muscarinic ligands
      of differing efficacy employ distinctly different pharmacophores when interacting
      with their specific receptor. Although the primary recognition element, the
      cationic head group, remains constant for all ligands, two H-bonding interactions
      are used selectively to stabilize agonist binding. In contrast, antagonists rely
      predominantly upon hydrophobic binding in the vicinity of the acetylmethyl group
      present in the endogenous transmitter. These ideas have been evaluated in the
      context of a three-dimensional model of the muscarinic receptor derived
      originally from bacteriorhodopsin. Together these studies have allowed
      speculations to be made regarding the sequence of events which lead to coupling
      to G-protein. Although an Asp residue on helix III of the seven-helical model is
      known to be involved as the primary recognition site for all ligands, a second,
      more deeply buried Asp on helix II is suggested to represent the ultimate agonist
      binding site from which receptor activation is triggered. Similar arguments are
      also applied to homologous receptor systems, in particular the beta-adrenergic
      receptor.

PMID- 1983088
TI  - Biology and prognostic factors of breast cancer.

PMID- 1983089
TI  - Novel chemotherapeutic agents in early clinical development.

PMID- 1983090
TI  - Multidrug resistance in human tumors.

PMID- 1983087
TI  - Biological activity of the mammalian RAP genes in yeast.
AB  - We have screened expression libraries for mammalian cDNAs capable of suppressing
      defects in ras1- Schizosaccharomyces pombe. Both the RAP1A and RAP1B genes were
      identified in this manner. They suppress defects in cell morphology and
      sporulation, although not conjugation. In contrast, RAP genes do not suppress
      phenotypes in the yeast Saccharomyces cerevisiae that are deficient in RAS.
      Indeed, expression of RAP1A appears to antagonize the activated S. cerevisiae
      RAS2val19 gene. These results indicate that RAP proteins can interact with RAS
      targets, sometimes productively, sometimes nonproductively.

PMID- 1983091
TI  - [DNA amplification (polymerase chain reaction) in microbiological diagnosis].

PMID- 1983093
TI  - Proceedings of the Second Congress of the European Society for Developmental
      Pharmacology. Como, Italy, May 17-19, 1990.

PMID- 1983092
TI  - [Headache diagnosis and vascular pathophysiology].
AB  - A new international headache classification has improved possibilities for
      uniformity of diagnosis throughout the world, because it gives operational
      diagnostic criteria for all headache disorders. The classification was an
      initiative of the International Headache Society, but has been supported by the
      Research Group on Headache and Migraine of the World Federation of Neurology and
      the main diagnosis entities have been used in the new International
      Classification of Diseases (ICD 10) by the WHO. Vascular mechanism of headache is
      only known in migraine. During attacks of migraine with aura pathognomonic
      changes in regional cerebral blood flow (rCBF) have gradually been characterized.
      The attack begins with occipito-parietal rCBF decrease which slowly spreads to
      involve a greater or smaller parts of one cerebral hemisphere. In the area of
      hypoperfusion the normal functional activation is abolished and response to
      altered PaCO2 is diminished. The autoregulation, however, seems to be preserved.
      Whether the area of hypoperfusion is actually ischemic is still uncertain. Later
      in the attack rCBF normalizes and then changes to become increased in the
      previously hypoperfused focus. Hyperperfusion persists for one to several hours.
      Headache begins during hypoperfusion and does not change with the later
      occurrence of hyperperfusion which may even outlast the headache. There is a
      strong correlation between the site of rCBF changes, the site of origin of aura
      symptoms and the laterality of headache. It is proposed that liberation of
      neurotransmitters sensitizes local nociceptors and thereby induces headache.

PMID- 1983094
TI  - Neurobehavioral changes produced by developmental exposure to benzodiazepines.
AB  - The results reported in this review show that prenatal and/or postnatal
      administration of benzodiazepines, at dose levels below those associated with
      overt signs of neurotoxicity, produces both short- and long-term alterations in
      rats. Most of these behavioral changes are characterized by altered activity
      patterns and emotional/motivational responsiveness to environmental challenges.

PMID- 1983095
TI  - Clinical observations in children after prenatal benzodiazepine exposure.
AB  - Eight children excessively exposed to benzodiazepines (BZD) in utero are
      described. Five of the 8 mothers admitted regular use of BZD and in 3 mothers,
      stored serum from early pregnancy could be analysed and found positive for BZD
      and its metabolite. All the children had similar dysmorphic features, in
      addition, 1 child had aplasia of one kidney and 2 had cleft palate. At follow-up
      2 children had become microcephalic. 2 were severely mentally retarded, 5 had a
      mild mental retardation and only 1 was of normal intelligence. In a case-control
      study, 4 neonatal diagnoses of congenital malformations, in our experience
      characteristic of fetal BZD exposure, were chosen as inclusion criteria. In 8 of
      18 cases, blood samples from early pregnancy were positive for BZD as compared to
      2 of 60 control samples. An association between BZD-positive serum tests and the
      particular diagnoses could be demonstrated (p = 0.00006).

PMID- 1983096
TI  - [Mantoux intradermal reaction and lymphocyte populations in asymptomatic HIV
      seropositive subjects].
AB  - Individuals who are infected with human immunodeficiency virus (HIV) are at high
      risk of developing tuberculosis, probably due to the reactivation of latent
      infection associated with HIV-induced immunosuppression. Tuberculin skin test is
      the best diagnostic means to assess a previous tuberculous infection, but this
      test may be falsely negative in HIV seropositive subjects. To assess the validity
      of a non-reactive tuberculin skin test in asymptomatic HIV seropositive subject,
      we performed Mantoux test 5 TU, chest x-ray, HIV serologic tests on 141
      asymptomatic prisoners. Determination of lymphocyte subsets in HIV seropositive
      carriers had already been performed. Chest x-ray film showed no pleuro-pulmonary
      lesion in any subject. We found 101 HIV seronegative subjects (89 men and 12
      women; 30 +/- 6 yrs with 18-39 range; 34 Mantoux reactive and 67 non-reactive)
      and 40 HIV seropositive individuals (30 men and 10 women; 29 +/- 6 yrs with 21-39
      range; 7 Mantoux reactive and 33 non-reactive). By subdividing HIV seropositive
      subjects in two groups (reactive and non-reactive to tuberculin test) a
      significant decrease of CD 4 lymphocytes and CD 4/CD 8 ratio was found in HIV
      seropositive/Mantoux non-reactive group, without changes in total lymphocytes and
      CD 8 subset. We conclude that: 1) a non-reactive tuberculin skin test cannot be
      confidently explained in asymptomatic HIV seropositive subjects with a T helper
      lymphocyte count decrease; 2) T helper cells are important to keep alive delayed
      hypersensitivity reaction.

PMID- 1983097
TI  - Monumental steps for oncology nursing 1975-1990. 15th annual Oncology Nursing
      Society Congress. May 16-19, 1990, Washington, D.C. Program and abstracts.

PMID- 1983099
TI  - [Apropos of the management of patients infected with HIV].

PMID- 1983098
TI  - Synergy between activated Leishmania major-specific CD4+ T lymphocytes and bone
      marrow-derived cells in the exacerbation of murine cutaneous leishmaniasis.
AB  - Mechanisms of exacerbation of murine cutaneous leishmaniasis mediated by
      Leishmania major-specific CD4+ T lymphocytes were studied. Using a limiting
      dilution assay for the quantification of Leishmania parasites, the infected
      tissues (footpad) of lethally irradiated mice were found to contain tenfold less
      parasites at four days of infection than the footpads of infected unirradiated
      animals. Injection of bone marrow cells depleted of T cells into irradiated mice
      at the site of infection led to an increase in parasite numbers to levels
      equivalent to those seen in unirradiated mice. After injection of either L. major
      specific CD4+ T cells, previously shown to exacerbate cutaneous leishmaniasis,
      into the infected footpad or the intravenous (i.v.) injection of bone marrow
      cells depleted of T cells, the numbers of parasites in lesions of irradiated mice
      never reached the values found in unirradiated control mice. In contrast, the
      concomitant transfer of CD4+ T-cell populations in situ and bone marrow cells
      depleted of T cells intravenously led to an increase in parasite loads in
      irradiated mice up to levels comparable to those of the unirradiated mice. This
      suggested that recruitment of myelomonocytic cells at the site of the lesions
      plays a role in the exacerbation of murine cutaneous leishmaniasis mediated by
      these CD4+ T lymphocytes. Finally, a similar effect was observed with T cells
      specific for an antigen unrelated to Leishmania, provided that this antigen was
      added to the L. major infecting inoculum.

PMID- 1983100
TI  - [Management and early treatment of patients infected with HIV. Synthesis of
      recommendations of an expert group convened by the french minister of Solidarite,
      Sante et Protection sociale].

PMID- 1983101
TI  - Takayasu's disease in an Ethiopian.
AB  - A 26-year-old Ethiopian woman with past history of stroke, presented with
      complaints of weakness, dyspnea on exertion, headache, and orthopnea. She had
      severe hypertension, asynchronous pulses, radial-femoral lag, cardiomegaly, and
      left ventricular hypertrophy. Blood studies were normal. Arteriogram in America
      showed aortic and mitral incompetence, bilateral subclavian occlusion distal to
      the origin of the vertebral arteries, with occluded hepatic and superior
      mesenteric arteries. The infrarenal abdominal aorta and common and external iliac
      arteries were occluded bilaterally. Renal arteries were normal. Takayasu's
      arteritis, inactive, was diagnosed. She underwent bilateral carotid-subclavian
      bypass, thromboendarterectomy of the abdominal aorta, and aorto-iliac bypass
      grafts. 3 years later she is greatly improved. This is the first report of
      Takayasu's arteritis from Ethiopia. International studies on the disease are
      summarized.

PMID- 1983103
TI  - Proceedings of the Second Congress of the International Society of Ocular
      Toxicology. Deidesheim, F.R.G., May 20-24, 1990.

PMID- 1983102
TI  - [In vitro studies of the adsorption behavior of Wofatit Y 88 in relation to
      various drugs].
AB  - The adsorber Wofatit Y 88 (VEB Chemiekombinat Bitterfeld) was tested regarding
      its adsorption properties in comparison with Hamoresin (B. Braun, Melsungen, FRG)
      Hemosorbent SKN-2K (USSR) and the own product Wofatit UH 91. As adsorptives the
      hypnotics Metaqualon, Pyrithyldion, Crotylbarbital and Phenobarbital were used.
      The investigation have been performed in a single-pass system in a relation of
      1:25 to the clinical practice conditions. The concentration measurements to the
      estimation of adsorbed amounts were made by UV-VIS spectrometry. It was found
      that Wofatit Y 88 is superior to Hamoresin with regard to adsorbed amounts and
      adsorption speed. For all drugs Wofatit Y 88 was superior to UH 91.

PMID- 1983104
TI  - The melanin binding of bisoprolol and its toxicological relevance.
AB  - Unexpectedly high accumulations of bisoprolol were detected in iris and ciliary
      body and in retina+choroid of beagles after 4 weeks of conjunctival and oral
      administration. This phenomenon gave reason to assume that these high
      concentrations in the pigmented structures of the eye might be related to melanin
      binding. According to literature a series of drugs, e.g. chloroquine,
      rifampicine, chlorpromazine, benzodiazepines, and also beta-adrenoceptor
      antagonists exhibit melanin-binding properties. By means of autoradiography it
      could be demonstrated in pigmented mice that after iv and po administration 14C
      labelled bisoprolol was selectively bound to the melanin-containing parts of the
      eye, irrespective of the mode of administration. Since the melanin-bound
      radioactivity could be extracted from the eye of mice and was eliminated with a
      t1/2 of approx. 7 days, the melanin binding of bisoprolol is considered to be
      reversible. Other beta-blocking agents like timolol and befunolol used already
      for a long time in the therapy of glaucoma have been reported to bind
      specifically to the melanin of the eye, and show comparable long half-lives,
      similar to bisoprolol. Usually, autoradiographic studies on drug distribution are
      performed with albino animals. This leads to a lack of information on melanin
      binding and may result in misinterpretation concerning the retention of
      substances, especially in pigmented compartments of the eye. Therefore, in
      autoradiographic studies of new investigational drugs during preclinical
      development, one should use both pigmented and albino animals.

PMID- 1983105
TI  - Bisoprolol--comparative toxicokinetic study after oral and conjunctival
      administration in beagles.
AB  - Beagles were treated with bisoprolol, a beta 1-selective adrenoceptor antagonist,
      for 30 days with the following daily doses: oral: 30 mg/kg; conjunctival: 0.5%
      solution (approx. 0.04 mg/kg) and 5% solution (approx. 0.4 mg/kg). Drug
      concentrations were determined in plasma and various eye tissues on days 1, 16,
      and 30, and on day 59, i.e. on day 29 of the follow-up period. Bisoprolol
      concentrations in plasma and most eye tissues were considerably higher after oral
      than after conjunctival treatment. The highest tissue concentrations were
      observed in the iris (+ciliary body) and retina (+choroid) with tissue/plasma
      concentration ratios between 100 and 150 after oral and 1000 to 3000 after
      conjunctival instillation (5% solution). In plasma no accumulation of the drug
      was observed which is in accordance with its plasma half-life of 4 to 5 h. In
      contrast to this, concentrations in the iris and retina increased from day 1 to
      day 16 and 30 by 3 to 8 times and the half-life of bisoprolol in these tissues
      was estimated to be between 3 to 5 days.

PMID- 1983106
TI  - Surface anesthetic effect and subjective compatibility of 2% carteolol and 0.6%
      metipranolol in eye-healthy people.
AB  - In a placebo-controlled, randomized, prospective, parallel, double-masked trail
      we study corneal sensitivity before and after application of 2% carteolol (20
      eyes) and 0.6% metipranolol (20 eyes). 2% carteolol does not decrease corneal
      sensitivity (no significant difference to the placebo group). 0.6% metipranolol
      leads to a decrease of corneal sensitivity up to 14 mg/S (median), lasting up to
      15 minutes. The local anesthetic effect is an important parameter for the
      subjective compatibility.

PMID- 1983108
TI  - Lens safety study with Picumast dihydrochloride--a double masked study using the
      Scheimpflug method.
AB  - A double-masked study was performed to investigate a possible side effect of the
      antiallergic substance Picumast dihydrochloride on lens transparency. 372
      patients with Picumast dihydrochloride- or Ketotifen-treatment regularly
      underwent ophthalmologic examinations and Scheimpflug photography of the anterior
      eye segment. Results of slitlamp examinations as well as microdensitometric
      analyzes of the film negatives after one year treatment did not reveal any
      evidence that Picumast dihydrochloride compromised lens transparency in humans.

PMID- 1983107
TI  - Case report: oxypertin-induced keratopathy?
AB  - A 45 year old caucasian female underwent longterm psychiatric treatment including
      Oxypertin. Ocular changes occurred in close time relation with the treatment of
      oxypertin: Corneal sicca-syndrome was found at first in both eyes, later on
      severe corneal scaring, vascularisation, and thinning indicated the need of
      further ophthalmologic treatment. Although the psychiatric treatment was stopped
      the ocular effects remained and keratoplasty had to be performed in the right
      eye. A case report is given to show the clinical and histopathologic aspect of
      the cornea in a patient undergoing treatment with a new designed and widely used
      neuroleptic drug.

PMID- 1983111
TI  - Drug interaction between cyclosporin A and nizatidine in Sprague-Dawley rats.
AB  - The H2-receptor antagonists seem to be effective in prevention and treatment of
      stress ulcer in transplant recipients. In a previous study on rats, an increase
      was observed in cyclosporinaemia and hepatotoxicity after administration of
      cimetidine or ranitidine in association with cyclosporin A (CyA). On the
      contrary, famotidine does not influence the blood CyA levels. The aim of the
      study was to detect the possible synergistic nephro- and hepatotoxicity of
      nizatidine administered in association with CyA, assaying the serum creatinine,
      the ALT and AST levels, and histological features of thirty young male Sprague
      Dawley rats, divided into 6 groups of five animals each. After 10 days, all the
      rats were sacrificed, their blood was collected to assay serum creatinine, ALT,
      AST and serum CyA levels: kidneys and livers were processed for light microscopy.
      The results obtained demonstrated that, while the level of creatinine was normal
      in each group, the average level of transaminase and the serum levels of CyA were
      significantly higher in the animals receiving the association of CyA and
      nizatidine. Furthermore, this group demonstrated a mild infiltrate of the liver
      characterized in some cases with eosinophilic polymorphonuclear cells. In light
      of the results obtained, it is probable that the increase of cyclosporinaemia is
      the consequence of an enhanced hepatotoxicity due to administration of CyA in
      association with nizatidine.

PMID- 1983109
TI  - Microtubule perturbation inhibits intracellular transport of an apical membrane
      glycoprotein in a substrate-dependent manner in polarized Madin-Darby canine
      kidney epithelial cells.
AB  - The effects of microtubule perturbation on the transport of two different viral
      glycoproteins were examined in infected Madin-Darby canine kidney (MDCK) cells
      grown on both permeable and solid substrata. Quantitative biochemical analysis
      showed that the microtubule-depolymerizing drug nocodazole inhibited arrival of
      influenza hemagglutinin on the apical plasma membrane in MDCK cells grown on both
      substrata. In contrast, the microtubule-stabilizing drug taxol inhibited apical
      appearance of hemagglutinin only when MDCK cells were grown on permeable
      substrata. On the basis of hemagglutinin mobility on sodium dodecyl sulfate gels
      and its sensitivity to endo H, it was evident that nocodazole and taxol arrested
      hemagglutinin at different intracellular sites. Neither drug caused a significant
      increase in the amount of hemagglutinin detected on the basolateral plasma
      membrane domain. In addition, neither drug had any noticeable effect on the
      transport of the vesicular stomatitis virus (VSV)-G protein to the basolateral
      surface. These results shed light on previous conflicting reports using this
      model system and support the hypothesis that microtubules play a role in the
      delivery of membrane glycoproteins to the apical, but not the basolateral, domain
      of epithelial cells.

PMID- 1983110
TI  - ATP-dependent and ATP-independent pathways of exocytosis revealed by
      interchanging glutamate and chloride as the major anion in permeabilized mast
      cells.
AB  - Most investigations of the mechanism of regulated exocytosis have involved the
      use of secretory cells permeabilized in glutamate-based electrolyte solutions. In
      our previous work we have used NaCl-based electrolyte solutions. For secretion to
      occur from rat mast cells under these latter conditions, a dual effector system
      comprising Ca2+ and a guanine nucleotide are required; together they are
      sufficient. Here we compare the secretion from mast cells permeabilized in
      solutions of different electrolytes. Replacement of Na+ by K+ had little effect.
      Replacement of Cl- by Br-, SO4-, gluconate, isethionate, acetate, tartrate,
      succinate, etc. affected the maximal extent of secretion elicited by the dual
      effectors Ca2+ and guanosine-5'-O-(3-thiotriphosphate) (Ca2(+)-plus-GTP-gamma-S)
      but had little influence on the effective affinity for Ca2+. The dicarboxylic
      amino acids (L- and D-glutamate, and L-aspartate) permitted exocytosis to be
      elicited by Ca2+ or GTP-gamma-S alone. Secretion stimulated by GTP-gamma-S is
      strongly inhibited by Cl- (50% inhibition by 20 mM Cl-), whereas the extent of
      Ca2(+)-induced secretion is proportional to the concentration of glutamate in
      mixed electrolyte buffers. Unlike dual-effector stimulation, secretion due to the
      single effectors requires adenosine triphosphate (ATP) and is prevented by
      inhibitors of protein kinase C. These results point to the existence of two
      parallel pathways for control of exocytosis in permeabilized cells, one ATP
      dependent, the other ATP independent.

PMID- 1983112
TI  - Weakening effect of famotidine but not of nizatidine on the mucus-bicarbonate
      barrier of the human stomach.
AB  - Twenty outpatients with various duodenal disorders but endoscopically normal
      gastric mucosa were randomly treated for 4 weeks with either nizatidine (300 mg
      h.s.) or famotidine (40 mg h.s.). Before and after treatment quantitative and
      qualitative evaluations of gastric mucus secretion as well as measurement of
      gastric bicarbonate output were performed. No changes in the mucus-bicarbonate
      barrier were observed after nizatidine treatment. In contrast, famotidine was
      found to impair the quality of mucus, thus weakening the mucosal defences against
      re-ulceration after treatment withdrawal.

PMID- 1983113
TI  - Homeotic genes regulate the spatial expression of putative growth factors in the
      visceral mesoderm of Drosophila embryos.
AB  - During Drosophila embryogenesis homeotic genes control the developmental
      diversification of body structures. The genes probably coordinate the expression
      of as yet unidentified target genes that carry out cell differentiation
      processes. At least four homeotic genes expressed in the visceral mesoderm are
      required for midgut morphogenesis. In addition, two growth factor homologs are
      expressed in specific regions of the visceral mesoderm surrounding the midgut
      epithelium. One of these, decapentaplegic (dpp), is a member of the transforming
      growth factor beta (TGF-beta) family; the other, wingless (wg), is a relative of
      the mammalian proto-oncogene int-1. Here we show that the spatially restricted
      expression of dpp in the visceral mesoderm is regulated by the homeotic genes Ubx
      and abd-A. Ubx is required for the expression of dpp while abd-A represses dpp.
      One consequence of dpp expression is the induction of labial (lab) in the
      underlying endoderm cells. In addition, abd-A function is required for the
      expression of wg in the visceral mesoderm posterior to the dpp-expressing cells.
      The two growth factor genes therefore are excellent candidates for target genes
      that are directly regulated by the homeotic genes.

PMID- 1983114
TI  - A Drosophila growth factor homolog, decapentaplegic, regulates homeotic gene
      expression within and across germ layers during midgut morphogenesis.
AB  - The decapentaplegic (dpp) gene product, a member of the transforming growth
      factor-beta family, is required in Drosophila embryos for normal gastrulation and
      the establishment of dorsal-ventral polarity in the embryo. dpp is also expressed
      at specific positions in the visceral mesoderm along the developing midgut. We
      find that mutations that eliminate the visceral mesoderm expression of dpp lead
      to defects in midgut morphogenesis and alter the spatially localized expression
      of the homeotic genes Sex combs reduced (Scr), Ultrabithorax (Ubx), and
      Antennapedia (Antp) in the visceral mesoderm. The extracellular dpp protein
      migrates from the visceral mesoderm across the apposing endodermal cell layer in
      a region of the endoderm that expresses the homeotic gene labial (lab).
      Mesodermal expression of dpp is required for the expression of lab in these
      endodermal cells indicating that dpp mediates an inductive interaction between
      the two germ layers. We propose that extracellular dpp protein regulates gut
      morphogenesis, in part, by regulating homeotic gene expression in the visceral
      mesoderm and endoderm of the developing midgut.

PMID- 1983115
TI  - Evidence for allelism of the recessive insertional mutation add and the dominant
      mouse mutation extra-toes (Xt).
AB  - A recessive mutant caused by insertional mutagenesis in transgenic mice has been
      detected in which the anterior part of the forelimb is disorganized. The
      morphology of the thumb is always altered and sometimes the adjacent finger has
      an extra phalanx. This phenotype suggests that a body plan gene is affected. We
      have named the mutation add (anterior digit-pattern deformity). Using the cloned
      DNA from the flanking region of the integrated transgene, add has been mapped
      close to the centromere of chromosome 13. This position links add to a
      genetically mapped locus called extra-toes (Xt). The phenotype of the double
      mutant add/Xt as well as the molecular analysis suggest that add and Xt are
      allelic.

PMID- 1983116
TI  - Expression of the murine homeobox-containing gene Hox-2.3 suggests multiple time
      dependent and tissue-specific roles during development.
AB  - This study reports the expression pattern of the murine homeobox-containing gene
      Hox-2.3 during development. Using in situ hybridization, we first detect Hox-2.3
      transcripts in the allantois primordium at 7.5 days post coitum (p.c.). One day
      later transcripts are found in embryonic ectoderm and mesoderm. In 9.5- and 10.5-
      day embryos Hox-2.3 expression is observed in the central nervous system (CNS)
      from a rostral boundary in the upper spinal cord to the caudal end. Within this
      anteroposterior domain, Hox-2.3 expression is also found in the peripheral
      nervous system, in the mesoderm and in the hindgut epithelium. The rostral
      boundary in the mesoderm is located at the level of the 11th somite and thus
      shifted posteriorwards compared to the rostral boundary in the neural tube.
      During subsequent development, the initially broad expression pattern in the
      somitic, lateral plate and intermediate mesoderm becomes restricted to structures
      in the urogenital system. In adults, the spinal cord and the derivatives of the
      Wolffian and Mullerian ducts continue to express the gene at a high level. The
      described temporal and tissue-specific changes in expression of Hox-2.3 are
      suggestive of several levels of regulation as reported for Drosophila homeotic
      genes and argue for more than one role of the gene during development and in
      adults.

PMID- 1983117
TI  - Expression and regulation of the abd-A gene of Drosophila.
AB  - We have developed a specific polyclonal antibody that recognizes the protein
      products of the abdominal-A (abd-A) gene, a member of the bithorax complex of
      Drosophila. The normal expression domain extends from parasegments 7 to 13, in
      good correspondence with previous genetic and molecular results. However, while
      the anterior border of expression is precisely demarcated by a parasegmental
      boundary, the posterior border does not coincide with a lineage boundary. Within
      the normal domain, the expression of abd-A shows intrametameric modulation; the
      amount of product is higher in posterior compartments and in the most anterior
      cells of the anterior compartments and then gradually decreases. We have examined
      the effect on abd-A expression of a number of mutations, some mapping within and
      others outside the abd-A transcription unit. Those mapping to the transcription
      unit eliminate or severely reduce the amount of abd-A antigen, while those
      mapping outside produce an abnormal distribution of abd-A protein. Finally, we
      show that the abd-A gene is down-regulated in part of the Abdominal-B (Abd-B)
      domain, precisely in those regions where the Abd-B gene is expressed at high
      levels.

PMID- 1983118
TI  - Blocking cell division does not remove the requirement for Polycomb function in
      Drosophila embryogenesis.
AB  - The Polycomb (Pc) gene is required from the extended germ band stage onwards, to
      maintain spatially restricted patterns of homeotic gene expression. It has been
      thought to be involved in the 'stable inheritance of the determined state'. In
      this paper, we have tested the notion that the Pc gene is required specifically
      during or after DNA replication to enable the stable transmission of states of
      gene activity. We found that arresting cell division using the string mutation or
      blocking DNA replication with aphidicolin failed to prevent ectopic expression of
      the homeotic gene Ultrabithorax in Pc mutants. Thus, even in the absence of DNA
      replication, Pc is required to maintain spatially restricted patterns of homeotic
      gene expression. The role of the Pc gene product in the stable repression of
      homeotic gene transcription is discussed.

PMID- 1983119
TI  - Abstracts of the Tenth Annual Conference on Computers in Anesthesia. New Orleans,
      Louisiana, 18-24 October 1989.

PMID- 1983120
TI  - Regulation of transmitter release at the squid giant synapse by presynaptic
      delayed rectifier potassium current.
AB  - 1. The three-microelectrode voltage clamp technique and pharmacological agents
      were used to examine the properties and functions of potassium currents in squid
      giant presynaptic terminals. 2. Outward currents consisted of two components: a
      slow component which activated over hundreds of milliseconds and was blocked by
      extracellular application of tetraethylammonium (TEA) ions and a more rapidly
      activating component which was relatively insensitive to extracellular TEA. 3.
      The more rapid component was studied in isolation by treating presynaptic
      terminals with extracellular TEA, as well as tetrodotoxin (to block sodium
      channel currents) and manganese (to block calcium channel currents). The
      magnitude of this current component was 1-2 mA cm-2 at 0 mV. Rates of activation
      and deactivation were voltage dependent and little evidence of inactivation was
      seen for depolarizations less than several seconds in duration. 4. The reversal
      potential of the current was -70 to -80 mV in normal saline and became more
      positive with elevated extracellular potassium concentrations, suggesting that
      potassium is the primary permeant ion. Accumulation of extracellular potassium
      appeared to be marked during depolarizations that produced significant activation
      of the current. 5. Extracellular application of 3,4-diaminopyridine (DAP) blocked
      the current with an apparent dissociation constant of 7 microM at 0 mV.
      Intracellular applications of DAP and TEA also were effective in reducing this
      current. These treatments, but not extracellular TEA application, broadened
      presynaptic action potentials and increased the magnitude and time-to-peak of
      postsynaptic currents elicited by the broadened presynaptic action potentials.
      Postsynaptic currents were a sensitive and linear function of action potential
      duration; a 30% increase in action potential duration increased postsynaptic
      current amplitude by 190%. 6. Estimation of the magnitude and time course of the
      presynaptic calcium current, based on previous measurements of calcium channel
      gating, indicated that action potential broadening produces a large increase in
      calcium current magnitude. These calculations predict that a 30% increase in
      presynaptic action potential duration will increase the peak amplitude of the
      calcium current by approximately 170% and the total amount of calcium entry by
      approximately 230%. This implies a linear relationship between transmitter
      release and calcium entry during an action potential and can be explained by
      assuming that calcium co-operatively triggers release within intracellular
      domains that do not overlap.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1983121
TI  - Inhibition of calcium currents by noradrenaline, somatostatin and opioids in
      guinea-pig submucosal neurones.
AB  - 1. Whole-cell recordings were made from submucosal neurones acutely dissociated
      from guinea-pigs. The actions of noradrenaline, somatostatin and [Met5]enkephalin
      on currents carried by calcium ions were studied. 2. On depolarization from a
      holding potential of -70 mV, an inward current activated at -40 mV, reached its
      peak amplitude at 10 mV and reversed to outward at 72 mV (with external calcium
      of 5 mM and internal caesium of 160 mM). 3. Cadmium, nickel and cobalt reversibly
      blocked the calcium current; concentrations causing 50% block were 2.5, 500 and
      2000 microM respectively. The calcium current (holding at -70 or -30 mV) was
      reversibly blocked by omega-conotoxin (100 nM), and unaffected by Bay K 8644 (0.1
      10 microM) and nifedipine (1 microM). Cadmium caused an outward shift in holding
      current at -30 mV, implying that there was a persistent inward calcium current at
      this potential. 4. Noradrenaline, somatostatin and [Met5]enkephalin decreased the
      calcium current. The maximal inhibition observed with any one agonist, or with a
      combination of two agonists, did not exceed 50%; concentrations giving half
      maximal inhibition were 5.5 microM for noradrenaline, 4 nM for somatostatin and 1
      microM for [Met5]enkephalin. The inhibition was independent of membrane
      potential. All three agonists also reduced the persistent calcium current at -30
      mV. 5. Inhibition of the calcium current by noradrenaline occurred with a latency
      of not less than 175 ms; cadmium applied by the same method depressed the current
      within 5-45 ms. 6. Experiments with selective agonists and antagonists indicated
      that the receptor types involved in calcium current inhibition were alpha 2
      adrenoceptors and delta-opioid receptors. Somatostatin acted at a distinct
      receptor. 7. Calcium currents were also inhibited by intracellular dialysis with
      guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S). Agonists were ineffective in
      cells pre-treated with pertussis toxin, but their action was restored when
      purified GTP-binding proteins (Go or Gi) were included in the intracellular
      recording solution. 8. It is concluded that noradrenaline, somatostatin and
      [Met5]enkephalin act at their respective receptors on guinea-pig submucosal
      neurones to inhibit a voltage-dependent calcium current. Activation of the same
      receptors also increases a potassium conductance in these cells: in both cases a
      pertussis-sensitive G protein is involved.

PMID- 1983122
TI  - Mechanisms underlying presynaptic inhibition through alpha 2-adrenoceptors in
      guinea-pig submucosal neurones.
AB  - 1. Intracellular recordings were made from submucosal neurones of the guinea-pig
      ileum. The actions of noradrenaline, somatostatin and [Met5]enkephalin on
      nicotinic synaptic potentials (EPSPs) were studied. 2. In one series of
      experiments, agonists were applied by superfusion; noradrenaline (0.1-20 microM)
      decreased EPSP amplitude by 95-100% in all neurones. Similar application of
      somatostatin (1-100 nM) inhibited EPSPs in about half the neurones by a maximum
      of 40%. [Met5]enkephalin (0.1-10 microM) did not alter EPSPs. Idazoxan and
      yohimbine competitively antagonized the action of noradrenaline with dissociation
      equilibrium constants of 20 and 30 nM respectively. 3. In another series of
      experiments, noradrenaline and somatostatin were applied locally from a pipette
      so that they reached presynaptic terminals but not the cell bodies or axons of
      the presynaptic cell: noradrenaline inhibited EPSPs by 90% in all neurones but
      somatostatin had no effect. When applied locally to the cell bodies giving rise
      to the presynaptic fibres, both agonists inhibited EPSPs in half the neurones by
      40%. 4. When noradrenaline was applied locally to presynaptic terminals, the
      latency to onset of noradrenaline to inhibit EPSPs was 45-160 ms; cadmium applied
      similarly depressed EPSPs in 5-50 ms. 5. Pertussis toxin pre-treatment only
      partially blocked presynaptic inhibition caused by noradrenaline but abolished
      the reduction of EPSP amplitude by somatostatin. 6. It is concluded that
      noradrenaline and somatostatin reduce the amplitude of the fast EPSP because they
      hyperpolarize cell bodies and prevent action potential initiation. Noradrenaline,
      but not somatostatin, has an additional action to inhibit acetylcholine release
      by acting at nerve terminal receptors. 7. The presynaptic inhibitory action of
      noradrenaline results from activation of alpha 2-adrenoceptors at nerve terminals
      but the mechanism(s) by which these presynaptic receptors act cannot be explained
      adequately by either activation of a potassium conductance and/or inhibition of a
      calcium conductance.

PMID- 1983123
TI  - Variation in strength of inhibitory synapses in the CA3 region of guinea-pig
      hippocampus in vitro.
AB  - 1. Simultaneous recordings were made from inhibitory cells located close to the
      stratum pyramidale and from pyramidal cells in the CA3 region of guinea-pig
      hippocampal slices, to examine inhibitory synaptic interactions. 2. The average
      amplitude of inhibitory postsynaptic potentials (IPSPs) initiated by single
      action potentials at different synapses varied between 0.3 and 2.6 mV.
      Experiments were performed to investigate the source of this variation. 3.
      Unitary IPSPs reversed at similar potentials to the first phase of the synaptic
      inhibition elicited by afferent fibre stimulation. IPSPs evoked by single action
      potentials or repetitive inhibitory cell firing were suppressed by picrotoxin, a
      gamma-aminobutyric acid (GABAA) receptor antagonists. 4. The time to peak and
      amplitude of averaged IPSPs were not related as predicted if amplitude variations
      resulted simply from different electrotonic locations of inhibitory terminals. 5.
      Transmission failures could be resolved at connections which generated small
      averaged IPSPs, but were not apparent at connections where averaged IPSPs were
      large. 6. IPSPs elicited by the same inhibitory cell in several pyramidal cells
      were of similar amplitude. The amplitudes of simultaneous IPSPs impinging on
      pairs of neighboring pyramidal cells were positively correlated. 7. Thus, the
      variation in efficacy of inhibitory synapses may result from differences in
      transmitter release from different inhibitory cells and not from postsynaptic
      factors.

PMID- 1983124
TI  - Intracellular mechanisms for alpha 1-adrenergic regulation of the transient
      outward current in rabbit atrial myocytes.
AB  - 1. The intracellular mechanism(s) underlying the decrease of a transient outward
      K+ current (It) induced by alpha 1-adrenergic agonists was studied in isolated
      adult rabbit atrial myocytes using whole-cell voltage clamp and cell-attached
      patch clamp techniques. Experiments were carried out at 22-23 degrees C. 2.
      Application of the specific alpha 1-adrenergic agonist, methoxamine, produced a
      decrease in It which was irreversible after the non-hydrolysable GTP analogues,
      GTP gamma S and Gpp(NH)p, had been introduced into cells via the recording
      micropipette. 3. Pre-treatment of cells with 0.1-0.15 microgram/ml pertussis
      toxin (PT) for 8-9 h at 30-34 degrees C did not prevent the alpha 1-induced
      decrease in It. Yet, this protocol, as measured by the PT-catalysed incorporation
      of [32P]ADP-ribose in membrane-associated 40 and 41 kDa proteins, effectively
      caused the ADP-ribosylation of approximately 70% of the PT-sensitive GTP-binding
      proteins (i.e. Gi) in these treated cells. After taking into account the
      proportion of non-viable cells (20-30%), the effectiveness of this treatment
      probably approaches 100% in the viable myocytes from which electrophysiological
      recordings were made. 4. Cell-attached patch recordings showed that bath
      application of methoxamine altered the single-channel events underlying It by
      decreasing their opening probability. Averaged currents from ensemble single
      channel openings recorded in the presence of 0.2 mM-methoxamine outside the patch
      reproduced the features of alpha 1-adrenergic modulation of the macroscopic It
      observed during whole-cell voltage clamp measurements. This observation provides
      evidence for the involvement of a diffusible intracellular second messenger in
      the alpha 1-adrenergic modulation of It. 5. The protein kinase C (PKC)
      activators, 4 beta-phorbol 12-myristate 13-acetate (PMA) and 1-oleoyl-2
      acetylglycerol (OAG) increased It, when included in the bath perfusate, whereas
      the inactive analogues, 4 alpha-phorbol and 4 alpha-phorbol 12,13-didecanoate,
      had no effect on It. 6. Exposure of cells to the PKC inhibitors, staurosporine
      and H-7, either by bath superfusion or intracellularly, via the recording
      micropipette, did not block the decrease in It produced by methoxamine. 7.
      Prolonged stimulation of atrial myocytes for 7-9 h at 22 degrees C with 500 nM
      PMA produced a 'down-regulation' of endogenous PKC activity, as well as a
      physical loss of the immunoreactive enzyme, as measured by an in vitro assay, and
      an anti-PKC monoclonal antibody, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1983125
TI  - Pharmacological evaluation of new alkylesters of 4-[(2-hydroxy-3
      alkylamino)propoxy]phenylcarbamic acids with beta-adrenolytic properties.
AB  - The basic relationship between the chemical structure and pharmacological
      activities of new alkylesters of 4-[(2-hydroxy-3
      alkylamino)propoxy]phenylcarbamic acids were evaluated. The efficiency of
      compounds was compared with those of metipranolol and practolol, respectively.
      The majority of 4-substituted derivatives of aryloxypropanolamines have shown
      antiisoprenaline (beta-adrenolytic) and local anesthetic (membrane stabilizing)
      activities. The values of LD50 and/or partition coefficients have not differed
      significantly when compared with those of standard metipranolol.

PMID- 1983126
TI  - Minor Symptoms Evaluation (MSE) Profile--a questionnaire for assessment of
      subjective CNS-related symptoms.
AB  - Minor Symptoms Evaluation Profile (MSE-profile) is an instrument for the
      assessment of subjective CNS-related symptoms and has recently been documented.
      This self-applied questionnaire includes 24 items and uses a visual analogue
      scale to record perceived symptoms. Based on a subjective grouping followed by a
      principal component analysis of the results of 374 individuals to confirm the
      grouping, 15 out of the 24 items were formed into three dimensions: Contentment
      (7 items), Vitality (5 items) and Sleep (3 items). The Cronbach's alpha
      coefficient used to evaluate the internal consistency of these dimensions was
      0.81, 0.81 and 0.77, respectively. Compared with the equivalent dimensions of
      other questionnaires for measurement of health-related quality of life, the
      dimensions of the MSE-profile were found to be relevant. Furthermore, the MSE
      profile showed good discriminative ability to distinguish symptom profiles of
      patients with other diseases/complaints than hypertension. It can be concluded
      that the MSE-profile is practically useful, reliable and sensitive enough for the
      assessment of subjective CNS-related symptoms that might affect the patient's
      well-being/quality of life.

PMID- 1983127
TI  - Quality of life/subjective symptoms during beta-blocker treatment.
AB  - beta-receptor antagonists have for many years been considered appropriate
      alternatives in the primary management of mild to moderate hypertension.
      Generally, they have been shown to be safe with a low frequency of serious side
      effects. Among the predictable and usually doserelated side-effects are
      bradycardia, bronchospasm, hypotension, muscle fatigue and cold extremities.
      Examples of unexpected side-effects are gastrointestinal symptoms such as nausea
      and disturbed intestinal motility, skin reactions, sexual dysfunction, as well as
      effects related to the central nervous system (CNS) such as emotional
      disturbances. The CNS-related side-effects, the mechanisms of which are unclear,
      consist of subtle effects on general well-being, decreased initiative, a
      depressed frame of mind and disturbed sleep. Generally, however, beta-blockers in
      therapeutic dosages do not affect the qualitative functions of the brain. Thus,
      all beta-blockers on the market seem to have high benefit-risk ratio, but
      independent of their physiochemical properties and pharmacodynamic profile, they
      seem to cause side-effects to about the same extent. The results so far available
      have been obtained by primarily using objective methods. Further comparison has
      now been initiated using documented subjective methods to investigate whether the
      objectively documented differences are of any clinical relevance to the patient's
      quality of life. Although it cannot be claimed with certainty, nonselective beta
      blockers seem to cause CNS-related side-effects to a greater extent than beta 1
      selective blockers. Differences in the degree of hydrophilicity of the beta
      blocker are apparently of no clinical relevance in this respect.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1983128
TI  - [Histochemistry of selected peptidases in small intestine mucosa in piglets
      experimentally infected with Isospora suis].
AB  - In the small intestine mucosa of 24 gnotobiotical piglets experimentally infected
      the first day post partum with oocysts of the coccidium Isospora suis, the
      activities of dipeptidylpeptidase IV (EC.3.4.14.5.; DAP IV) and gamma-glutamyl
      transferase (EC.2.3.2.2.; GGT) in the microvillous zone of enterocytes were
      evaluated by scanning densitometry. The tissue of the small intestine in piglets
      infected with a dose of 100,000 oocysts of the coccidia of I. suis was examined
      in the period from the first till the eleventh day post infection (DPI). In the
      control piglets at the age of 2-5 days it was found that most of the DAP IV
      activity was located in the microvillous zone of the enterocytes of the middle
      jejunum, rear jejunum and ileum. The DAP IV activity of duodenum mucosa was
      lower; as compared with the activity in the mucosa of the jejunum and ileum it
      reached 53-57%. In the case of GGT activity, the highest density values of the
      reaction product were recorded in the microvillous zone of enterocytes of the
      duodenum and the whole jejunum, the lowest in the ileum mucosa (86-89%) of the
      activity found in the duodenum and jejunum). During the experimental infection
      the infected piglets had a significant deficit of both peptidases, especially DAP
      IV (the whole studied period). The development of GGT activity was slightly
      different with the onset of the marked decline of the enzyme activity only on the
      fifth DPI. The lower GGT activity persisted till the eighth DPI. The density of
      the GGT reaction product began to return to the normal on the ninth to eleventh
      DPI. No predisposition in the location of the deficit was observed in the
      peptidases studied during the infection. The decline of the activity of both
      enzymes influenced also the mucosa of all studied parts of the small intenstine.
      The difference lay in the relevance of lowering of the density of reaction
      product of DAP IV and GGT on other DPI and in the different intensities of the
      return of the activity to the physiological normal.

PMID- 1983130
TI  - Papers from the Second International Symposium on Pharmaceutical and Biomedical
      Analysis. April 1990, York, UK.

PMID- 1983129
TI  - [Effects of submarine engine room steady noise on the compound action potential
      tuning curves and its relation to cochlear pathology in guinea pigs].
AB  - Compound Action Potential Tuning Curves (CAP-TC) for tone pip of 2k, 4 kHz were
      examined in 8 guinea pigs before and after exposure to noise with main energy
      centered in the range of 0.25-4.0 kHz. CAP-TC was measured with the pure tone
      simultaneous masking profiles. AP was evoked by tone pip with an intensity of 10
      dB above threshold. Masker level producing 40% reduction in AP amplitude was
      used. Relations between changes in CAP-TC and AP threshold shifts and the
      pathology of the stereocilia of hair cells were evaluated by surface preparation
      and SEM observation in 13 ears. After noise exposure, animals with damaged
      stereocilia showed AP threshold shift of 20-50 dB, deteriorations of CAP-TC,
      decrease of Q10 dB value, threshold shift of characteristic frequencies (CF) and
      displacement of CF towards higher frequencies. It showed that stereocilia damage
      may affect the susceptibility and frequency selectivity of the cochlea. We
      consider the CAP-TC may be an useful and sensitive index for detecting
      physiological and pathological conditions of the cochlea.

PMID- 1983131
TI  - Acid-base equilibria of beta-blockers in acetonitrile.
AB  - The acid-base equilibria of a series of beta-adrenoceptor blocking drugs in
      acetonitrile have been studied, and pKHB+ values determined. The theory of such
      titrations is discussed and simple potentiometric and visual methods in
      acetonitrile media are proposed for the assay of beta-adrenoceptor blocking
      drugs.

PMID- 1983132
TI  - Proton NMR monitoring of the onset and recovery of experimental renal damage.

PMID- 1983133
TI  - A pattern recognition approach to the comparison of PMR and clinical chemical
      data for classification of nephrotoxicity.

PMID- 1983135
TI  - Kidney, proteins and drugs. 6th International Symposium of Nephrology.
      Montecatini Terme, June 1-3, 1989.

PMID- 1983134
TI  - Genetic susceptibility to atherosclerosis.
AB  - Genetic factors are implicated in atherogenesis by family and twin studies of
      coronary artery disease, interacting with the environment to produce the
      phenotypic disease. Restriction fragment length polymorphisms provide useful
      linkage markers with which to study the genetics of this disease, the
      effectiveness of marker loci being characterized in terms of their polymorphism
      information content. Other forms of nucleotide variation, including variable
      number of tandem repeats can also provide linkage markers for aetiological loci
      and can be detected by the use of polymerase chain amplification followed by
      sequencing, denaturing gel electrophoresis, base pair specific chemical cleavage
      or the use of oligonucleotide probes. Linkage markers may be used either in
      population association or familial studies. Candidate genes may be studied or
      complete genomic mapping attempted. A review of potential candidate genes for
      atherosclerosis is presented.

PMID- 1983136
TI  - Polyaspartic acid protects against gentamicin-induced toxicity: mechanism of
      action.

PMID- 1983137
TI  - Application of a procedure starting with an HIV-I/HIV-2 mixed EIA.
AB  - A procedure to diagnose the infections by the human immunodeficiency virus type 1
      (HIV-1) and type 2 (HIV-2) was proposed. The specimens were first screened by a
      mixed enzyme immunoassay (EIA) for the presence of antibodies to HIV-1 as well as
      to HIV-2. Those screened positive were thereafter confirmed and differentiated
      their antibody reactivities toward the antigens of HIV-1 and HIV-2 by Western
      blot (WB). This procedure was found to be one hundred percent accurate to
      diagnose 66 coded specimens with well defined seroreactivities to HIV-1 from
      Centers for Disease Control (CDC). While its accuracy in HIV-2 antibody testing
      could not be evaluated in the present study owing to the lack of HIV-2 standard
      reference specimens. With this procedure, six out of each of two groups of 176
      foreigners and 719 individuals who visited the Taipei Municipal Venereal Disease
      Control Institute (TMVDCI) were screened repeatedly reactive by the mixed EIA. By
      WB only four of the first six and two of the second six were confirmed HIV-1
      positive. Their antibody reactivities toward HIV-2 antigens were either absent or
      significantly much lower than those toward HIV-1 antigens. Furthermore, none
      reacted to the env proteins gp160 and gp120 of HIV-2. We therefore concluded that
      out of the 895 test individuals, only six were confirmed infected with HIV-1.
      There were neither HIV-2 infections nor dual infections. The similar
      pathogenicity and trans mission of HIV-2 as of HIV-1 justify an equal
      appreciation for HIV-2 testing. The present study indicated that a procedure
      starting with a mixed EIA aimed to diagnose HIV-1 as well as HIV-2 did not have
      any adverse effects on HIV-1 testing.

PMID- 1983138
TI  - Paciforgine: a new macrolide antifungicidal isolated from Paciforgia sp-2.
AB  - A new macrolide, paciforgine, has been isolated from Paciforgia sp.-2. The
      structure of the new macrolide was determined by spectrometric methods.
      Paciforgine is active in vitro against Trichophyton verrucosum and Candida
      albicans.

PMID- 1983139
TI  - Plasma gastrin and somatostatin in newborn infants and their relationship to
      catecholamines.
AB  - We investigated the relationship between gastrin and somatostatin, and
      catecholamine concentrations in the cord blood of newborn infants. We also
      measured the levels of the two peptides during the first postnatal hours in the
      infants and furthermore characterized their molecular pattern. Twenty-two healthy
      infants who had been born at term were studied. Blood samples were collected from
      the umbilical cord and from the infants 0.5 h and 3.5 h after delivery. Peptides
      were measured with radioimmunoassay and further characterized by HPLC.
      Catecholamines were analysed by HPLC. We found that gastrin and somatostatin
      concentration in the umbilical cord blood was 106 +/- 40 pmol/l and 29 +/- 17
      pmol/l, respectively. A significant relationship between the concentrations of
      somatostatin and noradrenaline in cord blood was found, (r = 0.7, n = 11, P less
      than 0.01). No such relation was found for gastrin. No change occurred in gastrin
      concentrations postnatally. Somatostatin concentration in the blood collected
      from the infant 0.5 h and 3.5 h after delivery was 19 +/- 11 pmol/l and 16 +/- 7
      pmol/l, respectively. These concentrations were significantly lower (P less than
      0.01) compared to the level measured in cord blood. Circulating gastrin was found
      to correspond to non-sulphated gastrin-34 and somatostatin to both somatostatin
      28 and somatostatin-14. The proportion of somatostatin-28 was 30-40% and of
      somatostatin-14, 60-70%. We conclude that the somatostatin level, but not the
      gastrin level is influenced by the degree of fetal stress during labour, as
      evidenced by the relationship with noradrenaline. The gastrin level remained
      unchanged during the 3.5 h following delivery, whereas the somatostatin level
      decreased significantly during the same time.

PMID- 1983140
TI  - Plasma gastrin and somatostatin levels in infants during the first four postnatal
      days.
AB  - This study was designed to measure plasma gastrin and somatostatin levels in
      infants and to simultaneously investigate the infants' metabolic status as
      reflected by the body weight as well as by the blood levels of FFA, D-beta
      hydroxybutyrate and glucose. Healthy infants (n = 94) who were born at term were
      studied cross-sectionally during their first four days of life. We found that the
      gastrin concentration (mean +/- SD) on the first day of life was 118 +/- 37
      pmol/l. Subsequently the concentration decreased and reached its lowest value on
      the third day; 94 +/- 27 pmol/l (P less than 0.05). On the fourth day the mean
      concentration increased to the same level as on the first day. There was a
      significant (P less than 0.01) increase in somatostatin concentrations from 18 +/
      6 pmol/l on the first day to 26 +/- 7 pmol/l on the fourth day and the
      concentrations were highly related (P less than 0.0001) to postnatal age. We
      conclude that the decrease in gastrin concentration is probably related to the
      low volume of breast milk ingested during the first days after delivery, and
      therefore to the low secretory activity of the gastrin-producing cells. The
      infants' catabolic condition during that time was evidenced by the reduction in
      body weight, the decrease in plasma glucose level and the increase in FFA and D
      beta-hydroxybutyrate levels. The gastrin increase found on the fourth day
      reflects most likely, the change in breast milk availability which occurs with
      the establishment of lactation. The mechanisms controlling the release of
      somatostatin remains to be established.

PMID- 1983141
TI  - Variation in the THC content of illicitly imported Cannabis products--1984-1989.
AB  - The tetrahydrocannabinol (THC) content of more than 180 samples of fresh illicit
      Cannabis products, seized by H.M. Customs and Excise on entry into Great Britain
      and Northern Ireland over the period 1984-1989, has been determined by gas
      chromatography. The average THC content of herbal cannabis remained high due to
      good quality cannabis from Jamaica and the USA, but that of cannabis resin was
      slightly lower. Resin from Morocco has changed significantly in its physical
      appearance. There was no fresh seizure of cannabis oil in this period.

PMID- 1983142
TI  - Nanoparticle uptake by the rat gastrointestinal mucosa: quantitation and particle
      size dependency.
AB  - Polystyrene microspheres in the size range 50 nm to 3 microns were fed by gavage
      to female Sprague Dawley rats daily for 10 days at a dose of 1.25 mg/kg-1.
      Previous histological evidence of the uptake of these particles and their
      absorption across the gastrointestinal tract and passage via the mesentery lymph
      supply and lymph nodes to the liver and spleen was confirmed by analysis of
      tissues for the presence of polystyrene by gel permeation chromatography.
      Measurement of radioactivity of tissues following administration of 100 nm and 1
      micron I125-labelled polystyrene latex particles for 8 days was corroborative
      although less secure because of the potential lability of the labelled particles.
      The extent of absorption of 50 nm particles under the conditions of these
      experiments was 34% and of the 100 nm particles 26% (as measured by determination
      of polystyrene content), of which total, about 7% (50 nm) and 4% (100 nm), was in
      the liver, spleen, blood and bone marrow. Particles larger than 100 nm did not
      reach the bone marrow, and those larger than 300 nm were absent from blood. No
      particles were detected in heart or lung tissue.

PMID- 1983143
TI  - Dependence of the renal excretion of theophylline on its plasma concentrations
      and urine flow rate in asthmatic children.
AB  - The dependence of the renal excretion of theophylline on its plasma concentration
      and urine flow rate has been investigated in asthmatic children of either sex.
      One group (age 12.25 +/- 0.80, mean +/- s.d. n = 8) was given aminophylline
      intravenously (i.v.), while another (age 10.00 +/- 3.64 n = 14) was given a
      sustained release preparation of theophylline orally (single dose and repeated
      doses). Unchanged drug (11.6% +/- 1.75) was excreted in the urine corresponding
      to a renal clearance of 10.6 +/- 1.6 mL h-1kg-1. Time dependence of the renal
      clearance of theophylline was found only after i.v. administration. Dependence of
      the renal clearance on urine flow rate was found both after i.v. administration
      and at steady state, but not after a single oral dose of theophylline. After oral
      administration, renal clearance of theophylline was higher at steady state than
      after a single dose (0.58 +/- 0.06 L h-1 kg-1 vs 0.23 +/- 0.03 L h-1 kg-1), while
      urine flow rate was lower (1.1 +/- 0.5 mL min-1 vs 1.8 +/- 0.9 mL min-1). High
      correlation of theophylline plasma concentration and theophylline excretion rate
      was obtained in 10 of 14 patients after administration of a single oral dose of
      the preparation (r = 0.8567 to 0.9830). There was no dose dependence of the renal
      clearance of the drug either after a single dose, or at steady state.

PMID- 1983144
TI  - Regulation of sympathetic and parasympathetic receptor responses in the rat
      trachea by epithelium: influence of mechanical and chemical removal of
      epithelium.
AB  - Removal of the epithelial layer of rat tracheal tissue did not affect the
      methacholine-induced contraction of the tracheal smooth muscle, but attenuated
      the (-)-isoprenaline induced relaxation (expressed as percentage of the
      methacholine contraction). In this way the epithelial layer seemed to play a role
      in the maintenance of an autonomic balance between sympathetic and
      parasympathetic receptor responses. Incubation of rat tracheal tissue with cumene
      hydroperoxide (3 x 10(-5)-10(-3) M) resulted in a dose-dependent destruction and
      (partial) removal of the epithelial layer. Cumene hydroperoxide diminished
      muscarinic receptor responses of the rat trachea. Moreover, the autonomic balance
      between muscarinic and beta-adrenoceptor responses was affected. The effects of
      cumene hydroperoxide on receptor responses were more pronounced after epithelium
      removal. The protective role of the epithelial layer of pulmonary tissue against
      oxidative stress has therefore been emphasized.

PMID- 1983145
TI  - Effects of solvents and detergents on the contractions of isolated smooth muscle
      preparations.
AB  - In testing poorly soluble substances in-vitro on isolated organs, organic
      solvents and solubilizers are used to increase water-solubility. To facilitate
      selection of appropriate substances, the effects of eleven of these chemicals
      have been studied in the following isolated smooth muscle preparations: guinea
      pig ileum stimulated by carbachol, histamine, 5-HT or single field stimuli; rat
      fundus stimulated by 5-HT; and mouse vas deferens stimulated by noradrenaline or
      trains of field stimuli. Nine solvents (acetone, diethyleneglycol monoethylether,
      dimethyl sulphoxide, ethanol, glycerol, methanol, polyethylene glycol 400, 1,2
      propanediol, Tetraglycol (tetrahydrofurfurylalcohol polyethyleneglycolether)) and
      two detergents (Triton-X 100 and Tween 80) were examined. The vas deferens proved
      to be most resistant, whereas rat fundus and guinea-pig ileum were more sensitive
      to the effects of solvent when present from 1 to 10 g L-1. Most solvents caused
      non-specific, concentration-dependent reversible inhibition of contractions.
      Dimethyl sulphoxide in high concentrations increased the contractile responses of
      guinea-pig ileum stimulated by 5-HT and in both experiments with electrical
      stimulation. Polyethylene glycol 400 augmented the response of mouse vas deferens
      to electrical stimulation. Overall, 1,2-propylene glycol and polyethylene glycol
      400 had the least effect and can be used in a concentration of 3 g L-1, and in
      qualitative studies even up to 10 g L-1. Glycerol, both monohydric alcohols and
      dimethyl sulphoxide produced more intense effects and should not exceed
      concentrations of 1-3 g L-1. Stronger inhibition was caused by diethyleneglycol
      monoethylether, acetone and Tetraglycol, and the bath concentrations of these
      substances should not exceed 0.5-1g L-1. Of the detergents only Tween 80 is
      suitable as a solubilizer in smooth muscle preparations in-vitro, forming
      micelles at 10 mg L-1 a concentration tolerated by isolated organs in this study.

PMID- 1983146
TI  - Effect of anti-inflammatory drugs on the cardiotoxin-induced hind-paw oedema in
      rats.
AB  - Cardiotoxin, isolated from Naja naja atra venom, induced rat hind-paw oedema.
      This effect was suppressed by the pretreatment with dexamethasone or BW 755C, or
      subplantar co-injection with FPL 55712. Pretreatment with aspirin alone did not
      affect this response, while a significant reduction of cardiotoxin-induced paw
      oedema was achieved with aspirin in combination with diphenhydramine and
      methysergide. Subplantar co-injection of PAF antagonist, BN 52021 or L 652731,
      with cardiotoxin had no effect on paw oedema, whereas superoxide
      dismutase/catalase reduced this oedematous response. Cardiotoxin-induced paw
      oedema was also suppressed by pretreating the rats with isoprenaline.
      Pretreatment with rat anti-platelet plasma, which greatly reduced peripheral
      platelet count, did not affect cardiotoxin-induced paw oedema. Cardiotoxin did
      not trigger platelet aggregation or release reaction either in platelet-rich
      plasma or in washed platelet suspension. The oedematous response after subplantar
      co-injection of cardiotoxin with basic or acidic phospholipase A2 appeared to be
      only an additive effect. These results suggest that arachidonate metabolites, in
      which leukotrienes are most important, participated in cardiotoxin-induced paw
      oedema. Superoxide radical was also involved, while PAF and platelets showed
      little influence in this oedema effect.

PMID- 1983148
TI  - The disposition of a histidine decarboxylase inhibitor (S)-alpha
      fluoromethylhistidine in rats.
AB  - An amino acid analyser method using ninhydrin was developed for (S)-alpha
      fluoromethylhistidine (FMH) with a minimum quantitation limit of 0.2 microgram mL
      1. The assay was used to study the kinetics of FMH in rat. After bolus
      intravenous administration of FMH hydrochloride hemihydrate (50 mg kg-1), plasma
      concentration decreased biexponentially with half-lives of 4.4 and 32.7 min. The
      distribution volumes of the central and peripheral compartments were 127.4 and
      166.3 mL kg-1, respectively. The tissue concentration of FMH was highest in the
      kidney and also decreased biphasically. The FMH concentrations in other tissues
      were lower, but their tissue/plasma ratios of FMH increased continuously after
      FMH injection, indicating that FMH partitioned into these tissues and was lost
      from them very slowly.

PMID- 1983147
TI  - Measurement of protein synthesis by the phenylalanine flooding dose technique:
      effect of phenylalanine and anaesthesia on plasma electrolyte, enzyme and
      metabolite levels.
AB  - Ten minutes after an intravenous flooding dose of phenylalanine to rats, plasma
      sodium and calcium concentrations were slightly reduced (by 2-7%) but no effects
      on potassium or phosphate were observed. Creatine kinase activities were
      significantly increased by phenylalanine injection (by 39%), but alkaline
      phosphatase, alanine aminotransferase, lactate dehydrogenase and aspartate
      aminotransferase activities were unaltered. Plasma concentrations of total
      proteins, albumin, cholesterol, triglycerides, urea, creatinine and glucose were
      also unaffected. In the presence of anaesthesia, phenylalanine injection had
      almost identical effects, although the increase in creatine kinase activities did
      not reach statistical significance. Anaesthesia for 10 min reduced plasma
      potassium concentrations (by 27%), and calcium (by 5%), though phosphate and
      sodium were unaltered. The activities of lactate dehydrogenase, creatine kinase
      and aspartate aminotransferase were reduced by between 36-52%, but alkaline
      phosphatase and alanine aminotransferase activities were unaltered by
      anaesthesia. Plasma concentrations of total proteins and albumin were also
      reduced (both by 9%), but glucose concentrations were increased (by 33%).
      Anaesthesia had no other significant effects on cholesterol, triglycerides, urea
      or creatinine concentrations. The qualitative effects of anaesthesia in the
      presence of raised free phenylalanine concentrations were similar. It was
      concluded that, except for creatine kinase, determinations of plasma constituents
      in phenylalanine-injected rats could be made without overt interpretational
      errors. However, caution is required in interpreting data on plasma constituents
      from anaesthetized rats.

PMID- 1983149
TI  - Enantioselective structure-pharmacokinetic relationships of ring substituted
      warfarin analogues in the rat.
AB  - The enantiomer specific pharmacokinetics of ring substituted warfarin analogues
      have been studied in the rat after the administration of 2 mg kg-1 of the
      racemates. The stereoselective differences observed were due to stereoselective
      plasma protein binding and stereoselective intrinsic hepatic clearance. Greater
      binding was observed for the S-enantiomers except for 2'-substituted analogues
      where the R-enantiomers were more tightly bound. The stereoselectivity in the
      binding ranged up to a factor of about 4. All substituted warfarins showed a
      higher intrinsic clearance than warfarin. Enantiomer selectivity depended on the
      position of the substituent; warfarin and 3'-substituted analogues showed R
      greater than S; 4'- and 2' substituted warfarins showed S greater than R
      stereoselectivity. Exceptions to this generality were seen for 4'- methoxy- and
      4'-methylwarfarin which did not show stereoselective hepatic clearance.

PMID- 1983150
TI  - The measurement of internal pressure of ampoules and its application to
      commercial products.
AB  - This paper reports a method for determining the internal pressures of ampoules,
      from the head space and the change in volume on opening, as measured by
      displacement of water. Using this method, internal pressures of commercial
      ampoules were shown to be lower than atmospheric pressure. For example, the ratio
      of internal pressure to atmospheric pressure in a commercial ampoule of 5 mL
      distilled water was 0.884 at room temperature (23 degrees C).

PMID- 1983151
TI  - Dose-dependent decrease in rat plasma amino acids after acute administration of
      ethanol.
AB  - Male rats were given three different doses of ethanol in i.p. injections (0.66,
      1.33 and 2.00 g kg-1). A dose-dependent decrease in the concentrations of most
      plasma amino acids was observed. For the total amino acid concentration this
      decrease was 5, 16 and 22%, respectively, compared with a saline-treated control
      group. It has previously been suggested that the oxidation of ethanol plays an
      important role in the amino acid decreasing effect of ethanol. In this study the
      lowest dose used (0.66 g kg-1) was calculated to be high enough to keep the
      enzyme systems involved in ethanol oxidation saturated during the 60 min course
      of the experiment. The observation that the ethanol-induced decrease in plasma
      amino acid levels was more pronounced with higher ethanol doses indicates that
      not only the oxidation of ethanol but also ethanol itself is important in the
      effect of ethanol on plasma amino acid concentrations.

PMID- 1983152
TI  - Effect of gamma-irradiation on disposition of the local anaesthetic, carbisocaine
      in rabbits.
AB  - 14C Labelled carbisocaine, a local anaesthetic agent, has been administered
      intravenously in a dose of 2 mg kg-1 to rabbits 7 days after whole-body 60Co
      gamma-irradiation with a dose of 5 Gy (1.9 Gy min-1) and to control rabbits. The
      plasma carbisocaine concentration-time courses were approximated by biexponential
      equations. The estimated pharmacokinetic parameters obtained when the data were
      fitted to an open two-compartment model were significantly different for the
      irradiated group relative to control animals, indicating a radiation-induced
      slower elimination rate of carbisocaine: AUC: 0.37 vs 0.29% dose min mL-1, CLtot:
      109.8 vs 155.4 mL min-1, Vdss: 27.6 vs 33.2 mL kg-1, kel: 0.0259 vs 0.0307 min-1,
      MRT: 251.7 vs 214.6 min. The total excreted amount of 14C radioactivity in the
      irradiated group was lower in comparison with controls: 6.5 vs 8.7% in bile and
      18.3 vs 23.7% in urine. However, lower carbisocaine concentrations were recorded
      in the heart, lungs, liver, and kidneys of irradiated rabbits compared with
      controls.

PMID- 1983153
TI  - Evaluation of contraction time and recovery period as a parameter in the calcium
      antagonistic action on the K(+)-depolarized rat duodenum.
AB  - Verapamil, nifedipine, phentolamine, tolazoline, gentamicin and neomycin
      inhibited calcium-induced contractions of K(+)-depolarized duodenum of rat by
      shifting the concentration-response curves to the right. Non-competitive
      inhibitions were observed with trifluoperazine, lidoflazine, procaine and
      tetracaine. Lanthanum behaved as a partial agonist in this preparation, while
      nitroprusside was ineffective. Contraction times in the presence of the
      antagonists and recovery time of the Ca2+ responses after the removal of the
      antagonists from the bathing medium were evaluated. From the findings, it is
      suggested that the contraction time and the time required for tissue recovery
      after removal of a Ca2+ antagonist are parameters making K(+)-depolarized rat
      duodenum a potential tool for the evaluation of the pharmacological effects of
      Ca2+ antagonists.

PMID- 1983154
TI  - Effect of myrcene on nociception in mice.
AB  - Myrcene, a monoterpene isolated from lemon grass oil (Cymbopogon citratus) has
      been investigated for antinociception in mice by a low temperature (51.5 +/- 0.5
      degrees C) hot plate method and by the acetic acid-induced writhing test.
      Significant inhibition of nociception was seen in the tests with myrcene at doses
      of 10 and 20 mg kg-1 (i.p.) or at 20 and 40 mg kg-1 (s.c.), respectively. The
      antinociceptive effect was significantly antagonized by naloxone (1 mg kg-1) or
      yohimbine (2 mg kg-1). The results suggest that myrcene is capable of inducing
      antinociception in mice, probably mediated by alpha 2-adrenoceptor stimulated
      release of endogenous opioids.

PMID- 1983156
TI  - Oxidative deamination of aliphatic amines by rat aorta semicarbazide-sensitive
      amine oxidase.
AB  - Rat aorta semicarbazide-sensitive amine oxidase (SSAO) exhibits very high
      affinity in the deamination of an homologous series of aliphatic amines of 1 to
      18 straight chain carbon atoms. The Km value decreases substantially as the chain
      length of these amines increases. The Vmax values are higher for the short chain
      amines. Diamines are poor substrates for SSAO or are not acted upon by the
      enzyme. The substrate preference for SSAO differs from that for monoamine
      oxidase.

PMID- 1983155
TI  - Specific binding and clearance of [3H]dynorphin (1-13) in the perfused rat lung:
      an application of the multiple-indicator dilution method.
AB  - The clearance and binding of a kappa-selective opioid peptide, dynorphin (1-13),
      in the perfused rat lung has been examined, using the multiple indicator dilution
      method. More than 50% of [3H]dynorphin (1-13) entering the pulmonary circulation
      was eliminated by the lung during a single passage of a tracer dose. By contrast,
      when a high dose (100 microM) of dynorphin (1-13) was concomitantly injected,
      [3H]dynorphin (1-13) behaved like [14C]sucrose, an extracellular marker. The
      kinetic analyses of the pulmonary venous outflow curves of [3H]dynorphin (1-13)
      and [14C]sucrose at low and high doses of dynorphin (1-13) indicated that the
      initial uptake rate constant, extraction ratio and distribution volume of
      [3H]dynorphin (1-13) decreased significantly in the presence of a high
      concentration of unlabelled dynorphin (1-13). These results suggest that
      [3H]dynorphin (1-13) is eliminated by a saturable process and binds to a specific
      binding site in the perfused lung, which may be the kappa-type binding site. The
      multiple indicator dilution technique, in combination with a moment analysis, was
      successfully applied to demonstrate the specific binding and clearance of
      dynorphin (1-13) in the perfused lung.

PMID- 1983157
TI  - The (+)-enantiomer is responsible for the antiplatelet and anti-inflammatory
      activity of (+/-)-indobufen.
AB  - The racemic compound indobufen and its (+)- and (-)-enantiomers have been
      compared for their effects on blood platelet function and rat carrageenan
      pleurisy. The antiplatelet properties were studied in-vitro in human platelets by
      measuring the inhibition of platelet aggregation and generation of serum
      thromboxane (Tx) B2. In-vivo, the antiplatelet and anti-inflammatory properties
      were studied in rats by measuring the inhibition of serum TxB2, the amount of 6
      keto-PGF1 alpha in pleural exudate and pleural exudate volume. In all tests the
      (+)-enantiomer was slightly more potent than the racemate, while the (-)
      enantiomer was far less potent. In the same rats, treatment with the lowest doses
      of the compounds giving 90% inhibition of serum thromboxane B2 generation was
      associated with occasional macroscopic lesions of the gastric mucosa.

PMID- 1983158
TI  - H1- and H2-histamine receptor blockers and opiate analgesia in mice.
AB  - In this paper, the interactions between opiates and antihistaminic compounds,
      both H1- and H2-blockers, were studied. CD1 mice were used, treated with saline,
      morphine CHl (5 mg/kg), and 1 or 10 mg/kg of the H1-antihistaminics
      tripelennamine, chlorpheniramine, diphenhydramine and cyclizine and the H2
      antihistaminics ranitidine and cimetidine, all compounds by s.c. route. Using the
      hot-plate test, it was observed that the two doses of tripelennamine and the
      higher doses of chlorpheniramine and cimetidine had antinociceptive activity.
      This increase on analgesia was also observed after chronic treatment with all H1
      antihistaminics (10 mg/kg, 3 times daily for 4 days). When antihistaminics were
      administered with morphine, it was observed that only ranitidine (10 mg/kg)
      blocked opiate analgesia. On the other hand, previous administration of the
      opiate antagonist naloxone (1 mg/kg) blocked the antinociceptive action of
      tripelennamine and chlorpheniramine (10 mg/kg) in control mice. In morphine
      dependent mice (by s.c. implantation of a 75-mg morphine pellet), a single
      injection of diphenhydramine or ranitidine blocked the analgesic action of
      morphine. Chronic administration of all antihistaminics did not modify morphine
      analgesia. These data are discussed in relation to the possible binding to the
      opioid receptors by antihistaminics and their facility in crossing the blood
      brain barrier.

PMID- 1983159
TI  - [Primary endocrine tumors of the liver and extrahepatic bile ducts].

PMID- 1983161
TI  - [Biosynthesis of somatostatin].

PMID- 1983160
TI  - The significance of the peroxides increase in the plasma of the patients with
      liver failure.
AB  - 200 patients with varied types of liver failure were biochemically and clinically
      investigated. Beside the usual biochemical analyses (transaminases, glutamyl
      transpeptidase, triglycerides, bilirubin), some special parameters such as lipid
      peroxides, glutathione, ceruloplasmin and the total antioxidative capacity of
      plasma were measured. High levels of lipid peroxides appear especially in severe
      cases of liver failure such as acute viral hepatitis, coma. The persistence of a
      high level of peroxides in plasma suggests the presence of severe, irreversible
      lesions. The increase of peroxides in the plasma is mainly due to the overridden
      production of antioxidative systems, localized especially in the liver. In severe
      liver failure, the mechanism of the increased formation of peroxides seems to
      involve bilirubin, due to induction of liver heme oxygenase. The data presented
      showed inverse correlations between the increase of peroxides and the decrease of
      glutathione and ceruloplasmin.

PMID- 1983162
TI  - [New mechanism of action of neurotransmitters].

PMID- 1983163
TI  - [Neoplastic pathology of the colon. Symposium].

PMID- 1983164
TI  - [Alpha-1 inhibition. Knowledge and prospectives].
AB  - Increased vascular peripheral resistances is the most frequent hemodynamic
      modification found in arterial hypertension. Arterial vasodilators therefore seem
      to be an appropriate therapeutic mean in this pathology. Alpha inhibitors to
      which prazosin belongs are potent arterial vasodilators. Prazosin's new galenic
      form will allow a larger therapeutic field.

PMID- 1983165
TI  - [Alpha-1 inhibition and blood pressure regulation].
AB  - The Alpress LP osmotic tablet enables progressive and prolonged release of
      prazosin into the digestive tract over a 16 hour period. This leads to the
      maintenance of stable plasma concentrations of the drug and the absence of high
      plasma peaks during the absorption of prazosin. The antihypertensive effect
      prazosin persists throughout the day and night, ensuring effective blood pressure
      regulation and treatment is well tolerated by patients.

PMID- 1983166
TI  - New approaches in bone marrow transplantation: the utilization of hematopoietic
      stem cells.
AB  - A detailed review of various methods of bone marrow transplantation is presented.
      Special emphasis is placed on the newest reports of fetal bone marrow
      transplantation in utero and stem cell reconstitution.

PMID- 1983167
TI  - [Beta-blockers in collyria and their secondary effects].
AB  - Beta-blockings in collyrium are much used in ophthalmology, in the treatment of
      chronic glaucoma with open angle, because they decrease the OT with 25-30%. They
      are well accepted, but have systemic effects. The collyria are drained by the
      lacrimal system and 80% of the product is absorbed by the nasal mucosa. If the
      active substance penetrates into the circulatory system, avoiding hepatic
      metabolization, it reaches the target organs in a rather considerable amount and
      leads sometimes to adverse effects, as a consequence of blockage of the specific
      receptors. Although these effects are not frequent in the usual practice, they
      might decompensate a poor cardiac or respiratory function. The physician has to
      take into account the cardio-respiratory state of the patients and to recommend
      concomitantly drugs that lower the myocardial conduction or contractibility.

PMID- 1983168
TI  - Involvement of beta-adrenergic receptors in the differential release of
      gonadotropins in acutely orchidectomized rats.
AB  - To determine the differential release of gonadotropins in acutely orchidectomized
      rats, a single injection of the beta-adrenergic blocker Bornaprolol (FM 24) was
      administered to the animals and plasma FSH and LH levels were determined. FM 24
      produced low plasma FSH levels only when injected 16 h before starting the blood
      collection and had no effect on FSH levels at 0, 30 and 46 h after its
      administration. However, it produced low LH plasma levels at 0, 16 and 30 h after
      administration. These findings confirm that pituitary beta-adrenergic receptors
      are involved in plasma LH release and suggest that they could also be involved in
      the differential release of FSH/LH.

PMID- 1983169
TI  - Serum gamma-glutamyl transpeptidase in chronic extrahepatic cholestasis.
AB  - Studies in the literature have shown the inhibitory action of bilirubin on serum
      gamma-glutamyl transpeptidase (GGT) activity. In spite of this, GGT is a
      sensitive diagnostic indicator, comparable to alkaline phosphatase for the
      diagnosis of chronic extrahepatic cholestasis (CEHC). To evaluate the
      relationship of bilirubin, alkaline phosphatase (AP) activity and GGT activity in
      CEHC we studied 30 patients with CEHC divided into two groups: A, 14 male and
      female subjects with serum bilirubin levels of 2 to 10 mg/dl, and B, 16 male and
      female subjects with serum bilirubin levels of 10.1 to 44 mg/dl. Serum GGT
      activity was measured by diluting serum samples 1:5 and 1:10. GGT values were
      equivalent in the two groups, there was no correlation between bilirubin and GGT
      (r = +0.179, P less than 0.01), and there was a significant correlation between
      GGT and AP (r = +0.627, P less than 0.01). The present results show that, if GGT
      inhibition by bilirubin did occur, this inhibition was not sufficient to prevent
      the increase in serum GGT levels and that the sensitivity of GGT as a marker for
      CEHC is similar to that of alkaline phosphatase.

PMID- 1983171
TI  - Symposium on toxins. Proceedings of the 37th symposium on toxins. Shiobara, Nasu,
      Tochigi, July 16-18, 1990.

PMID- 1983170
TI  - Expression of intercellular adhesion molecule-1 in murine allergic contact
      dermatitis.
AB  - Intercellular adhesion molecule-1 (ICAM-1) plays an important role in the
      interaction of immunocompetent cells in inflammation. It contributes to
      lymphocyte recruitment, antigen presentation and T-cell activation. Recently, the
      murine homologue of ICAM-1, originally designated as MALA-2, has been identified.
      The monoclonal antibody YN1/1.7 for murine ICAM-1 enables the analysis of ICAM-1
      expression in murine allergic contact dermatitis, a prototype of cutaneous T-cell
      mediated inflammatory response. At 0, 1, 8, 24, 48, 72 h, and 7 and 14 days after
      challenge with 2,4-dinitrofluoro-1-benzene (DNFB) cryostat sections of ear skin
      were immunostained for ICAM-1, I-A and mononuclear cells (L3T4, Lyt-2, BM8). In
      normal skin ICAM-1 labeling was restricted to endothelial cells and dermal
      dendritic cells/macrophages; keratinocytes (KCs) did not express ICAM-1. The
      dermal cellular infiltrate increased progressively from 8 to 72 h after DNFB
      challenge. The majority of infiltrating cells were BM8+ macrophages (75%) and
      L3T4+ (10%) or Lyt-2+ T cells (10%); maximally 30% of those stained positive for
      ICAM-1. At 24 h, focal ICAM-1 expression on KCs developed, reached a maximum at
      72 h and faded thereafter. Migration of T cells into the epidermal layer started
      at 48 h at sites which had already expressed ICAM-1. Our data provide evidence
      that expression of ICAM-1 by epidermal cells precedes infiltration of the
      epidermis by T lymphocytes as shown before in human cutaneous disorders. Thus, a
      mouse model may be useful to investigate the role of ICAM-1 in inflammation
      further.

PMID- 1983172
TI  - [Unusual migration of the testis].

PMID- 1983173
TI  - [The characteristics of the morphological changes in the gastric mucosa in
      duodenal peptic ulcer, ulcer recurrence after vagotomy and in the Zollinger
      Ellison syndrome].
AB  - Results of morphometry and count of certain kinds of endocrinocytes of gastric
      mucosa are analyzed. Pronounced proliferative alterations of the gastric mucosa
      were found with clear signs of the increased function of the structures
      responsible for acid gastric secretion. In part of the patients with ulcer
      disease of the duodenum there are considerable changes in the amount of certain
      kinds of endocrinocytes of the antral portion of the stomach, which form
      accumulations in the form of different fields and even focal zones. Such
      alterations in the gastric mucosa have correlative relationships with the level
      of acid gastric secretion.

PMID- 1983174
TI  - [Lichen planus: etiopathogenesis].
AB  - Lichen planus could result from a succession of immunological events: stimulation
      of Langerhans cells and keratinocytes by foreign antigen--production of
      interleukin 1 (IL 1)--activation, attraction and multiplication of helper T
      lymphocytes--production of interferon gamma--appearance of intercellular adhesion
      molecule-1 (ICAM 1) and HLA DR Antigen on keratinocytes membranes, allowing
      adhesion of T lymphocytes to keratinocytes and subsequent destruction of the
      latter.

PMID- 1983175
TI  - Role of the major capsid protein in herpes simplex virus type-1 capsid assembly.
AB  - Two herpes simplex virus type 1 (HSV-1) temperature-sensitive (ts) mutants with
      defects in the gene for the major capsid protein, ICP5, were examined for their
      effects on virion capsid assembly. Polyacrylamide gel electrophoresis revealed
      that both mutants were able to synthesize wild-type (WT) levels of ICP5 at the
      nonpermissive temperature. However, the 53 kD capsid protein disappeared
      concomitant with the appearance of a new, 51 kD species. These results, taken
      together with ultrastructural and immunological analyses indicate that the
      processing and assembly of capsid proteins, DNA packaging and thermal stability
      of HSV-1 virions are dependent upon functional ICP5.

PMID- 1983177
TI  - Inhibition of neutrophil functions by scrapie prion protein: description of some
      inhibitory properties.
AB  - The effect of scrapie prion protein (PrP) either in the native or in the
      denatured form was studied on in vitro responses of human neutrophils. Incubation
      of neutrophils with native PrP caused an inhibition of their aggregation induced
      by cytochalasin B. Moreover, the denatured form was in itself a strong
      aggregation inducer. When evaluating the effect on generation of neutrophil
      superoxide anion (O2) we found that neutrophils released O2 in response to the
      denatured from only but the native form was ineffective. Similarly, neutrophil
      discharge of beta-glucuronidase which represents the azurophilic granule marker
      was stimulated in a dose-dependent form by the denatured PrP 27-30 whereas the
      native form was almost completely devoid of any activity. These results indicate
      that several aspects of neutrophil function can be altered by the native form of
      prion protein PrP 27-30. This might be responsible for the impaired phagocytic
      cell activity explaining, at least in part, the absence of any inflammatory
      reaction during scrapie infection.

PMID- 1983176
TI  - Localization of 2',3'-decycling phosphodiesterases in the Newcastle disease virus
      virion.
AB  - Purified Newcastle disease virus (NDV) virions possess 2',3'-cyclic nucleotide 2'
      phosphohydrolase (2'-CNPase) and 2',3'-cyclic nucleotide 3'-phosphohydrolase (3'
      CNPase) activities. These enzyme activities cannot be removed from the virion
      even after extensive purification by chromatography on controlled-pore glass. In
      the intact virion, the 3'-CNPase activity was stimulated by Triton X-100, while
      the 2'-CNPase activity was partially inhibited. We have prepared the NDV subunits
      and have shown that 3'-CNPase was associated exclusively with the viral
      nucleocapsid. In contrast, the 2'-CNPase activity was associated with both the
      envelope as well as the nucleocapsid. A threshold amount of both enzyme
      activities was detected in viral M protein.

PMID- 1983178
TI  - Electron microscopy, immune electron microscopy, enzyme immunoassay and
      immunofluorescent evaluation of rotaviruses isolated from individual calves and
      piglets.
AB  - Rotaviruses were isolated in primary bovine foetal kidney cells from 3 of 13
      (23.1%) tested suckling calves and from 3 of 14 (21.4%) suckling piglets both
      suffering of acute diarrhoea, as confirmed by serological tests. The presence of
      rotaviral antigen in culture supernatant was revealed by double sandwich enzyme
      immunoassay (EIA) and direct immunofluorescence (IF). Transmission electron
      microscopy (TEM) and immune electron microscopy (IEM) showed particles with an
      average diameter of 70 nm. The strains adapted to continuous pig kidney cells PK
      15 have lost their reactivity in EIA, although TEM revealed the presence of
      rotavirions.

PMID- 1983179
TI  - Production of alpha-interferon by human leukocytes.
AB  - We examined the capacity of human leukocytes to produce alpha-interferon subtypes
      following viral induction. It was shown that the beta-propiolactone inactivated
      viral inductor stimulated the production of a complete set of native alpha
      interferon subtypes. Acid treatment of native interferon at pH 2.0 inactivated
      the acid-labile portion of alpha-interferon. Its exposure to 37 degrees C for 5
      days and repeated acid treatment at pH 2.0 resulted in additional inactivation of
      some interferon pool fractions. The acid-labile subtypes of human alpha
      interferon were formed in a nonadherent mononuclear cell fraction.

PMID- 1983180
TI  - Longitudinal study of natural foci of Central European encephalitis virus in West
      Slovakia.
AB  - A total of 2922 small terrestrial mammals of 12 species were collected in six
      localities of West Slovakia between 1981 and 1986. When examined for the
      prevalence of neutralizing antibodies (NA) to Central European encephalitis (CEE)
      virus we found that 14.6% had antibody. Nearly all (97%) of the 426 animals with
      antibody were Clethrionomys glareolus, the most abundant species (52.6% of
      mammals collected, 15.1% of those with antibody). Apodemus flavicollis (22.5% of
      mammals collected, 18.1% of those with antibody), Apodemus sylvaticus (14% of
      mammals collected, 8.5% of those with antibody), and Microtus arvalis (5.5% of
      mammals collected, 3.3% of those with antibody). In all locations studies the
      most abundant tick found on small mammals was Ixodes ricinus (larvae and nymphs).
      Less abundant, but present in all studied sites, were larvae and nymphs of
      Dermacentor reticulatus and Haemaphysalis concinna. Six strains of CEE virus were
      isolated from tissues of animals: four from Clethryonomys glareolus and one each
      from Apodemus flavicollis and Sorex araneus. Three of six isolates were from
      animals collected in February; none of the six had detectable neutralizing
      antibody to CEE virus. We discuss these observations with regard to possible
      mechanisms of persistence of CEE virus.

PMID- 1983182
TI  - The analysis of some indices of immune response, DNA repair, and micronuclei
      content in cells from tick-borne encephalitis patients.
AB  - Patients with tick-borne encephalitis (TBE) had higher counts of red blood cells
      (RBC) with micronuclei. The majority of patients revealed decreased capacity of
      blood lymphoid cells for DNA repair except those with a 2-wave pattern of the
      course of disease; in the latter, the DNA repair was significantly higher than in
      healthy donors. Patients with TBE revealed lower T-lymphocyte counts due to a
      decrease in the amount of T-helper cells (the level of T-suppressors was
      elevated). The intensity of antibody production against TBE virus was
      significantly enhanced by termination of disease in the majority of patients. The
      count of natural killer cells was decreased, particularly at the initial stage of
      disease. At the time of admission to hospital the counts of RBC with micronuclei
      and of T-helper cells were in reverse proportion. At the terminal stage of
      disease the same correlation was noted between RBC counts with micronuclei and
      the antibody level. At the onset of disease a direct correlation was noted
      between DNA repair and B-lymphocyte and T-helper counts. At the final stage of
      disease the reverse correlation between the activity of DNA-repair systems and T
      suppressor counts was registered. Three months after discharge from hospital, the
      indices of micronuclear test, natural killer cell activity, and DNA repair
      returned to normal.

PMID- 1983181
TI  - Alterations of arginase activity in scrapie-infected mice and in amyotrophic
      lateral sclerosis.
AB  - We followed the dynamics of arginase activity, the ultrastructural changes, and
      accumulation of the scrapie agent in the CNS of scrapie-infected mice. The
      arginase activity has been shown to increase 5-fold within the first 3-4 months
      of the incubation period followed by subsequent fall at its end. The peak of
      increased arginase activity coincided with appearance of multilayer membranes,
      whereas the decrease of this activity was associated with the greatest
      development of status spongiosus, synaptic degeneration, accumulation of five
      layer membranes as well as with maximal accumulation of the scrapie agent in the
      CNS. Examination of 100 patients with different forms of amyotrophic lateral
      sclerosis (ALS) revealed a 2-8-fold increase of arginase levels in the
      cerebrospinal fluid (CSF) as compared with the background levels in the
      comparative groups of control patients. Similar enzyme alterations in scrapie-
      and in ALS--are discussed in terms of possible resemblance of their pathogenesis.

PMID- 1983183
TI  - Dot ELISA for direct detection of BK virus in urine samples.
AB  - The dot ELISA technique was applied for direct detection of BK virus in clinical
      urine samples. The assay was performed on nitrocellulose paper dotted with the
      polyethylene glycol precipitated urine samples free of cellular debris. BK virus
      was detected with an anti-BK virus monoclonal antibody, and the complex was
      visualized by immunoperoxidase staining. Positive reaction appeared as well
      defined dark blue spots. Of the 110 urine samples examined, 31 were positive in
      the dot ELISA and 79 proved negative. Comparing with the IIF results, the dot
      ELISA had a 88.46% of sensibility and 90.4% of specificity, and the results
      agreed completely in 99 samples. The simple dot ELISA technique can be
      recommended for detection of BK virus excretion in routinary diagnostic.

PMID- 1983185
TI  - Properties and use of mumps viral antigen for detection of specific IgG and IgM
      antibodies in enzyme-linked immunosorbent assay.
AB  - Specific mumps virus antigens of three purification degrees have been prepared
      and their quality was evaluated in the enzyme-linked immunosorbent assay (ELISA)
      with specific human sera. Two enzyme immunoassays were elaborated, namely a
      simple sandwich method for IgG and the IgM-capture technique for IgM detection.
      Four different lots of mumps antigen were tested in these two ELISA systems. All
      antigens of corresponding purification degrees showed practically the same
      properties.

PMID- 1983184
TI  - Equine herpes virus 1 and pseudorabies virus resistance to 2'-fluoropyrimidine
      analogs and to bromovinyldeoxyuridine: implications for dTMP kinase activity.
AB  - The 2'-fluoropyrimidine nucleoside analogs 1-(2-deoxy-2-fluoro-beta-D
      arabinofuranosyl)-5-iodocytosine (FIAC). 1(2-deoxy-2-fluoro-beta-D
      arabinofuranosyl)-5-methyluracil (FMAU), and 1(2-deoxy-2-fluoro-beta-D
      arabinofuranosyl)-5-iodouracil (FIAU) showed higher in vitro activity against
      herpes simplex virus type 1 (HSV-1), than equine herpesvirus 1 (EHV-1) or
      pseudorabies virus (PRV). Comparison of the 50% plaque inhibitory doses for HSV-1
      and its mutant MMdUr-20 in cell cultures with inhibition constants (Ki's) for the
      viral deoxythymidine kinases (dTKs) suggests that in the infected cell FMAU is
      phosphorylated by host enzymes. As compared to HSV-1, EHV-1 and PRV were more
      resistant to E-5-(2-bromovinyl-2'-deoxyuridine (BVdU) and to the 2'
      fluoropyrimidine analogs, as are HSV-2 and the HSV-1 mutants MMdUr-20 and S1.
      Because the dTKs of the latter lack deoxythymidylate kinase (dTMPK) activity,
      there appears to be a correlation between resistance to these analogs and BVdU on
      the one hand, and lack of dTMPK activity on the other. We predict that EHV-1 and
      PRV dTKs will be shown to lack significant dTMPK activity.

PMID- 1983186
TI  - Dhori virus induced lesions in mice.
AB  - Dhori and Thogoto viruses are till now the only recognized tick-borne
      orthomyxoviruses. Like Thogoto virus, also Dhori is highly hepatotropic for
      laboratory mice; the lesions in several organs resemble those described for
      influenza virus.

PMID- 1983187
TI  - Arboviruses in the Iberian Peninsula.
AB  - The information concerning the presence and activity of arboviruses in the
      Iberian Peninsula is very scanty. In Portugal serological studies have been done
      with sera from animals, wild birds and human population. The results have shown
      that some arboviruses have been active in some areas of the territory. West Nile
      (WN) virus was isolated from mosquitoes and Dhori and Thogoto viruses have been
      isolated from ticks. In Spain, in spite of the large territory, it's geographical
      contiguity to Africa and the existence of different kinds of climates and
      ecologic conditions, the information is reduced to some surveys done in some
      restricted regions of the country. In both countries African swine fever was
      frequent and recently African horsesickness has been introduced to Southern
      Spain. A straight liaison and cooperation among virology laboratories of both
      countries and also Morocco should be emphasized in order to establish
      epidemiological surveillance in Southern Europe.

PMID- 1983188
TI  - HIVs and the simian-human connection: mysteries and controversies.

PMID- 1983189
TI  - Investigations of magnesium, histamine and immunoglobulins dynamics in acute
      urticaria.
AB  - In 42 urticaria patients, magnesium, histamine and IgE were dosed. Magnesium, IgE
      and histamine variations were followed in urticaria evolution, during acute phase
      and clinical remission. We noticed magnesium, histamine, IgE values variations
      depending on disease evolution and applied therapeutic scheme. Therefore: At
      disease starting point, histamine presented 3.5 times higher values than the
      normal ones. The value decreases following a curve which tends to reach normal
      values during clinical remission. At disease starting point, magnesium presented
      values under the inferior limit of the normal, 0.5 m mol/L respectively, as a
      mean. The value increases towards the normal limit during clinical remission.
      Immunoglobulins E follow a similar curve to histamine one, presenting 1,250 U/L
      values at the starting point, that, under medication, influence decrease between
      normal limits (800 U/L), during clinical remission. Analyzing the variations of
      biochemical parameters, the authors emphasize magnesium substitution treatment in
      urticaria.

PMID- 1983190
TI  - [Conjunctival contamination in orthopedic surgery].
AB  - Operating theatres expose health workers to close contact with body fluids and
      thus to the risk of contracting blood-borne infections. The conjunctiva of the
      eye offers a portal of entry for infection; an abrasive mixture of bone, marrow
      and blood propelled at high speed by power tools and reamers could damage any
      epithelial surface. 100 consecutive operations were studied and contaminating
      particles were counted on the glasses lens. 67% out of 100 times the surgeon's
      and the assistant's glasses were contaminated. Orthopaedic surgeons work in a
      high-risk environment and should protect themselves against possible
      contamination of the conjunctiva by wearing glasses with broad lens.

PMID- 1983191
TI  - Molecular and genetic characterization of two pollen-expressed genes that have
      sequence similarity to pectate lyases of the plant pathogen Erwinia.
AB  - A set of cDNAs that are expressed in tomato anthers were isolated. We further
      characterized two of these cDNAs (LAT56 and LAT59) and their corresponding
      genomic clones. LAT56 and LAT59 show low levels of steady-state mRNA in immature
      anthers and maximal levels in mature anthers and pollen. The LAT56 and LAT59
      genes are single-copy in the tomato genome, and are linked on chromosome 3,
      approximately 5 cM apart. Although these cDNAs did not cross-hybridize, their
      deduced protein sequences (P56 and P59) have 54% amino acid identity. The LAT56
      and LAT59 genes each have two introns, but they are located in non-homologous
      positions. P56 and P59 show significant protein sequence similarity to pectate
      lyases of plant pathogenic bacteria. The similarity of P56 and P59 to the
      bacterial pectate lyases is equivalent to the homology described for different
      pectate lyase sequences of the genus Erwinia. We suggest that the pollen
      expression of LAT56 and LAT59 might relate to a requirement for pectin
      degradation during pollen tube growth.

PMID- 1983192
TI  - Inhibitory effect of different anticoagulants on gamma-glutamyl transpeptidase
      activity.
AB  - Increased gamma-glutamyl transpeptidase (GGT) levels have been observed in
      patients with several types of liver diseases. However, since GGT activity can be
      inhibited or increased by several substances, the interpretation of these
      increased levels should be made with caution. The present study was designed to
      determine plasma GGT activity in blood samples obtained from 24 adult volunteers
      (13 males and 11 females aged 20 to 40 years) with the use of three different
      anticoagulants, i.e., ethylenediaminetetraacetic acid (EDTA), calcium fluoride
      and calcium citrate, and to compare it with GGT activity in serum obtained from
      the same blood samples. Serum GGT activity was significantly higher than plasma
      GGT activity (P less than 0.001) and significantly higher in men than in women (P
      less than 0.05), though plasma GGT activity was similar for both sexes.

PMID- 1983193
TI  - Independent and cooperative behavior of Thy1 and CD3:TcR T cell signalling
      pathways.
AB  - Normal resting spleen T lymphocytes from mice were stimulated in vitro by
      monoclonal antibodies (mAbs) against either Thy 1 or CD3:TcR surface protein
      molecules. Although both mAbs were mitogenic, anti-Thy 1 activation generated 5
      times more IL2 secretion than anti-CD3 activation under similar conditions.
      Production of IL3-like activity was comparable for both Thy1 and CD3-mediated
      activation. In addition, non-mitogenic doses of anti-CD3 and anti-Thy1 (0.16
      micrograms/ml and 0.0125% ascites, respectively) mAbs induced T cell activation
      when provided together. These results indicate that Thy1 signalling cooperates
      with the CD3:TcR pathway to activate T cells. However, the Thy1 pathway is also
      regulated independently since IL2 production is larger when stimulated by anti
      Thy1 than anti-CD3 mAbs.

PMID- 1983194
TI  - DNA variants of alpha-1-antitrypsin in rheumatoid arthritis with and without
      pulmonary complications.
AB  - Restriction fragment length polymorphisms (RFLPs) of alpha-1-antitrypsin were
      studied in 99 subjects with rheumatoid arthritis alone, 21 subjects with
      rheumatoid arthritis and pulmonary fibrosis, 26 subjects with rheumatoid
      arthritis and bronchiectasis, and 86 controls. No associations with either
      rheumatoid arthritis itself or with the associated pulmonary disorders were noted
      in this U.K. Caucasoid population.

PMID- 1983195
TI  - Extended HLA haplotypes in multiplex families with insulin dependent diabetes
      mellitus in Tunisian population: HLA serological typing and RFLP analysis.
AB  - Haplotypes including HLA A, B, C, DR, and DQ were compared in a study population
      comprising 18 Tunisian multiplex families with diabetic children. Eighty
      haplotypes found in IDDM patients were compared with 148 haplotypes present in
      healthy family members. RFLP analysis showed that two DR subtypes were
      significantly more common in the diabetic haplotypes (DR4-DQw8: 82 per cent in
      IDDM members compared to 0 per cent in healthy members, p less than 0.001 and DR
      Dw25: 56 per cent in IDDM patients compared to 16.7 per cent in healthy members,
      p less than 0.001) and these were in most cases found in haplotype combinations
      with HLA A2 B44 DR4 DRw53 and HLA A 24 B18 DR3 genes, respectively.

PMID- 1983196
TI  - Southern blot analysis of DNA extracted from paraffin wax-embedded tissue.
AB  - Genetic analysis of multi-generation families using RFLP is often incomplete
      because fresh tissue is not available for the isolation of DNA. However, in many
      instances archival material exists, usually formalin-fixed in paraffin blocks.
      Procedures have been described for extracting DNA from such specimens. Many
      parameters affect the quality of the DNA eventually extracted and this in turn
      determines whether the DNA can be successfully digested with restriction enzymes
      and probed (Dubeau et al., 1986; Warford et al., 1988). In essence, the
      procedures followed at the time of fixation largely determine whether archival
      material will yield useful results. We have re-examined the effect of varying the
      fixation time but, more importantly, we have assessed the validity of RFLP
      results obtained from fixed tissue.

PMID- 1983197
TI  - Adrenal tyrosine hydroxylase activation in the developing rat: influence of the
      thyroid status.
AB  - Adrenal tyrosine hydroxylase activation was elicited in developing control, hypo-
      and hyperthyroid rats by insulin-hypoglycaemia. Rats were deeply anaesthetized
      with chloroform at a low concentration, since intrinsic tyrosine hydroxylase
      activation was very low with this technique, as compared to Ketamine injection or
      chloroform at a high concentration. The study of time-course of tyrosine
      hydroxylase activation showed that the maximum value was observed 2 h after
      insulin administration. In control animals, tyrosine hydroxylase activation
      increased between 4 and 20 days, and then decreased. Hypothyroidism is associated
      with a decreased tyrosine hydroxylase activation between 4 and 50 days, as
      compared to controls and hyperthyroidism with an increased activation between 6
      and 30 days. While tyrosine hydroxylase from saline-treated rats exhibits two
      different forms (with two apparent Km values for the cofactor), enzyme from
      insulin-treated animals was present in a single form with a Km corresponding to
      the low Km value of the saline-injected rats. At 6 and 14 days, hypothyroidism
      increases tyrosine hydroxylase Km values as compared to euthyroid animals.

PMID- 1983198
TI  - Improving prognosis of aortitis syndrome.

PMID- 1983199
TI  - Silent thyroiditis with thyroid-stimulation-blocking antibodies (TSBAb).
AB  - A 24-year-old man showed thyrotoxic symptoms with hypokalemic periodic paralysis.
      Serum thyroid hormone levels were high and thyrotropin (TSH) was undetectable.
      123I-thyroidal uptake was suppressed. TSH-binding inhibitor immunoglobulin (TBII)
      was positive. After a month without any treatment, he became hypothyroid. Thyroid
      hormone level was decreased and TSH was increased to above the normal range. 123I
      thyroidal uptake was increased. TBII activity was still positive. From the
      clinical findings, a diagnosis of silent thyroiditis was made. Sera obtained in
      the hypothyroid state revealed the presence of thyroid-stimulation-blocking
      antibodies (TSBAb), but there were no thyroid-stimulating antibodies (TSAb).
      These results suggest that the hypothyroidism in this patient was due to the
      presence of TSBAb with TBII activity.

PMID- 1983200
TI  - Angiographic anatomy and pathogenic mechanisms of angina pectoris: implications
      regarding medical therapy.

PMID- 1983201
TI  - Characteristics and clinical significance of silent myocardial ischemia during
      ambulatory electrocardiographic monitoring in patients with ischemic heart
      disease.

PMID- 1983203
TI  - Oral immunization using recombinant bacteria. International symposium. Munich,
      June 6-7, 1990. Proceedings.

PMID- 1983202
TI  - Fimbriae of Escherichia coli as carriers of heterologous antigenic sequences.

PMID- 1983204
TI  - Kynurenate and 2-amino-5-phosphonovalerate alter the spinal seizures evoked by
      sudden cooling of toad isolated cords.
AB  - Sudden cooling of the isolated spinal cord of toads results in characteristic
      seizure-like activity in the hindlegs. In the present investigation, kynurenate
      (KYN), a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist and 2
      amino-5-phosphonovalerate (APV), a competitive NMDA receptor antagonist, were
      tested in the pattern, latency and duration of the spinal seizures. APV, 1.3-2.5
      mmol/kg and KYN, 2.6 mmol/kg, inhibited the tonic phase of the spinal seizures
      and prolonged the duration of the clonic phase after intralymphatic (i.l.)
      administration. The same effect was observed after intrathecal injection of
      either 10 or 20 mumol/20 microliter of each drug. The clonic phase was markedly
      attenuated by KYN at high doses of 5.3 or 10.6 mmol/kg, i.l., suggesting that non
      NMDA receptors may have some mediation in the generation of that phase. Both
      antagonists retarded the onset of seizures indicating that activation of NMDA
      receptors is likely involved in the beginning of this convulsive-like activity.
      This model may be a useful technique to assay other excitatory amino acid
      antagonists.

PMID- 1983205
TI  - [Psychotropic drugs and sexuality].

PMID- 1983206
TI  - Happy families. Phytochrome properties and biological action: A NATO Advanced
      Research Workshop, Chichester, UK, July 22-27, 1990.

PMID- 1983207
TI  - PLC and PKC: a tale of two messengers. Receptor-mediated stimulation of
      phosphoinositide metabolism and protein kinase C, Sixth International Symposium
      on Cellular Endocrinology sponsored by the W. Alton Jones Cell Science Center,
      Lake Placid, NY, USA, August 12-15, 1990.

PMID- 1983208
TI  - The normal erbB-2 product is an atypical receptor-like tyrosine kinase with
      constitutive activity in the absence of ligand.
AB  - Overexpression of the erbB-2/neu gene is frequently detected in human cancers.
      When overexpressed in NIH 3T3 cells, the normal erbB-2 product, gp185erbB-2,
      displays potent transforming ability as well as constitutively elevated levels of
      tyrosine kinase activity in the absence of exogenously added ligand. To
      investigate the basis for its chronic activation we sought evidence of a ligand
      for gp185erbB-2 either in serum or produced by NIH 3T3 cells in an autocrine
      manner. We demonstrate that a putative ligand for gp185erbB-2 is not contained in
      serum. Chimeric molecules composed of the extracellular domain of gp185erbB-2 and
      the intracellular portion of the epidermal growth factor receptor (EGFR) did not
      show any transforming ability or constitutive autophosphorylation when they were
      expressed in NIH 3T3 cells. However, they were able to transduce a mitogenic
      signal when triggered by a monoclonal antibody directed against the extracellular
      domain of erbB-2. These results provide evidence against the idea that an erbB-2
      ligand is produced by NIH 3T3 cells. Furthermore, we obtained direct evidence of
      the constitutive enzymative activity of gp185erbB-2 by demonstrating that the
      erbB-2 kinase remained active in a chimeric configuration with the extracellular
      domain of the EGFR, in the absence of any detectable ligand for the EGFR. Thus,
      under conditions of overexpression, the normal gp185erbB-2 is a constitutively
      active kinase able to transform NIH 3T3 cells in the absence of ligand.

PMID- 1983209
TI  - Genetic behaviour of tumorigenicity in human cancer.
AB  - The technique of somatic cell hybridization and the concept of tumour suppressor
      genes share a common history. Somatic cell hybrids between mammalian tumour cells
      and their normal cellular counterparts invariably are non-tumorigenic,
      establishing the recessive genetic nature of tumorigenicity. The development of
      cytogenetics and microcell hybridization has provided methods for localization of
      the tumour suppressor genes to specific chromosomal regions. Continuing studies
      of this type will facilitate the isolation of these genes by molecular methods
      including differential cDNA screening and 'reverse genetics'.

PMID- 1983210
TI  - Molecular genetic aspects of glial tumour evolution.
AB  - Cancer can be viewed as a dynamic process driven by the cellular accumulation of
      genetic alterations that provide selective growth advantage. Such alterations can
      be classified as one of two fundamental types: acquired (cancer-affective,
      dominant) or eliminated (cancer suppressive, recessive). This review considers
      genetic alterations that occur during the development of the most common type of
      central nervous system tumour, glioma.

PMID- 1983211
TI  - Multiple endocrine neoplasia.
AB  - The recent chromosomal mapping of the genes for two different autosomal dominant
      inherited predispositions to multiple endocrine neoplasias promises to be a
      significant breakthrough for the understanding of the pathogenesis of such
      lesions. Multiple endocrine neoplasia type 1 (MEN1) associates primary
      hyperparathyroidism, lesions of the endocrine pancreas and pituitary adenomas.
      The first hint that the MEN1 gene is localized on chromosome 11 came from the
      finding of allele losses in MEN1 associated tumours. Subsequent genetic linkage
      analysis to restriction fragment length polymorphism (RFLP) markers assigned the
      gene to chromosome band 11q13. MEN2A is characterized by medullary thyroid
      carcinoma and phaeochromocytoma. The disease locus was localized to the
      centromeric region of chromosome 10 by genetic linkage. For both syndromes
      genetic linkage maps of the flanking regions have been established, and a set of
      RFLP markers is now available for premorbid identification of gene carriers in
      affected families. Analysis of allele losses showed that tumorigenesis of
      parathyroid and pancreatic lesions results from unmasking of a recessive mutation
      at the MEN1 locus, and by deletion mapping the tentative MEN1 region was
      restricted to a few million base pairs. In contrast, such losses appear to be
      relatively rare in MEN2A associated lesions.

PMID- 1983212
TI  - Domoic acid toxicity. Proceedings of a symposium. Ottawa, Ontario, 11-112 April
      1989.

PMID- 1983213
TI  - Neurotoxic effect of domoic acid: mediation by kainate receptor
      electrophysiological studies in the rat.
AB  - Domoic acid, an excitatory amino acid structurally related to kainic acid, has
      recently been identified as being responsible for the severe intoxication
      presented, in 1987, by more than 150 people having eaten mussels grown in Prince
      Edward Island. The present in vivo electrophysiological studies, using unitary
      extracellular recordings obtained from pyramidal neurons of the CA1 and of the
      CA3 regions of the rat dorsal hippocampus, were undertaken to study the effect of
      kainic acid and domoic acid applied by microiontophoresis and compare their
      potencies to that of agonists of the 2 other subtypes of glutamatergic receptors
      or neuropeptides. The activation induced by domoic acid and kainate was more than
      20-fold more potent in the CA3 than in the CA1 region, whereas no such regional
      difference could be detected with all the other substances tested. In the CA1 as
      well as in the CA3 region, domoic acid was about 3 times more potent than
      kainate. A selective lesion of the mossy fibre system originating from the
      dentate gyrus and projecting to the CA3 region of the dorsal hippocampus,
      drastically reduced the excitatory effect of kainic acid and domoic acid in this
      later area, without affecting the response to the other substances tested.
      Several class of pharmacological agents were studied in an attempt to find an
      antagonist of kainate and domoic acid. Only benzodiazepines could selectively
      suppress the neuronal activation induced by kainate, however, with a lower
      efficacy in the CA3 than in the CA1 region. These results demonstrate that domoic
      acid is a potent agonist of kainate receptors and that, in the CA3 region, it
      might produce its neurotoxic effects through activation of kainate receptors
      located on mossy fibre terminals. Finally, in the event of a new wave of
      intoxication, our results suggest that a rapid treatment with high doses of
      benzodiazepines could possibly prevent the important and irreversible hippocampal
      damage.

PMID- 1983214
TI  - Efficacy of topical oxatomide in women with pruritus vulvae.
AB  - Pruritus vulvae is a very common condition. The patient's scratching often
      worsens the situation and makes diagnosis by the clinician difficult. A clinical
      trial to assess the safety and efficacy of a topical antihistaminic drug
      (oxatomide) was carried out. The first stage aimed to determine the best
      formulation and concentration: eleven patients were admitted in the study,
      conducted openly. Two preparations (cream and gel) and two concentrations (2.5%
      and 5%) were tested. A second stage was performed to assess the efficacy of
      oxatomide gel 5% versus placebo: thirty patients entered a double-blind, cross
      over, placebo-controlled study. Results of the first stage demonstrated good
      local tolerability of the medication, good patient acceptance and no side
      effects. During the second stage better anti-itching action of topical oxatomide
      than placebo was obtained. Safety and acceptability were confirmed. In general
      topical oxatomide showed good tolerability and efficacy in women with vulvar
      itching of various natures.

PMID- 1983215
TI  - [Role of neuroexcitatory amino acids in memory processes. Study with gamma-L
      glutamyl-L-aspartic acid].
AB  - Convergent data demonstrate that excitatory amino acid systems (glutamate and
      aspartate) participate in synaptic plasticity of the central nervous system.
      Their action is mediated by at least three subclasses of receptors which have
      been characterized on the basis of their selective affinity to N-methyl-D
      aspartate (NMDA), quisqualate and kainate. NMDA receptors appear to be directly
      involved in the induction of long-term potentiation (LTP) at the hippocampal
      level, and quisqualate/kainate receptors in the expression of LTP. This suggests
      that excitatory amino acid systems may have an important role in learning and
      memory. However, how these systems interfere with memory processes remains
      largely unknown. We have isolated a pseudopeptide, gamma-L-glutamyl-L-aspartate
      (gamma-LGLA) (Ungerer et al., 1988), which has the pharmacological properties of
      a competitive antagonist at NMDA receptors as evidenced by biochemical studies
      and by the fact that gamma-LGLA selectively blocks the clonico-tonic seizures
      induced by NMDA, while having no significant action against seizures induced by
      kainate or quisqualate. Elsewhere, gamma-LGLA is devoid of toxicity at the doses
      used. Behavioral effects of gamma-LGLA were first studied in a Y-maze avoidance
      learning task. Animals had to leave the start alley within 5 sec. (temporal
      component) and to choose the left alley of the maze (spatial component) to avoid
      footshock. They underwent one trial every minute and were trained to a criterion
      of 7 correct out of 8 consecutive trials. Retention was tested either 1 h, 3 h,
      6h, 24 h, 7 days or 21 days after acquisition.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1983216
TI  - [Atypical neuroleptics. Review of the available clinical data].
AB  - Pharmacological treatment of schizophrenia in based in the hypothesis that
      disturbances in central dopaminergic (DA) systems, i.e. increased DA-activity in
      the mesolimbic system, are involved in the pathogenesis of these psychotic
      disorders. Since neuroleptics exert a broad spectrum of pharmacological
      activities, during the last decade efforts have been undertaken to develop new
      antipsychotics, separating their antipsychotic action from their extrapyramidal
      (EPS) effects. Neuroleptics with this kind of properties have been designated
      atypical, although being a rather heterogenous group. In fact, some of the
      atypical antipsychotics are selective with respect to neurotransmitter system or
      regional brain activity like the benzamides, while others are non-selective at
      all such as the dibenzodiazepine derivate clozapine, and interfere with different
      receptor systems. In general, the atypical antipsychotics can be divided among
      two groups: DA-selective compounds and receptor non-specific agents. Of the DA
      selective compounds, the group of the benzamides form a distinct chemical class,
      of which sulpiride has been the most thoroughly investigated, followed by
      remoxipride. Concerning the antipsychotic effects of the benzamides, sulpiride as
      well as remoxipride have been demonstrated to be equipotent as compared to
      classical neuroleptics like chlorpromazine and haloperidol, without however
      inducing either EPS or anticholinergic symptoms of importance. With respect to
      the dibenzodiazepine derivate clozapine, it has been demonstrated that this
      compound has not only potent antipsychotic properties but, more important, may be
      effective in severely ill treatment resistant patients, without most probably the
      risk of inducing EPS. Finally, the series of compounds, characterized by
      serotonin -S2- and dopamine -D2- antagonistic properties may be of importance,
      albeit they do not meet the presently common definition of atypicality.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1983217
TI  - Somatostatin analogue (SMS 201-995) decreases plasma levels of corticotropin
      (ACTH) and corticotropin-releasing hormone in a patient with ectopic ACTH
      producing tumors.
AB  - Effects of long-acting somatostain analogue (SMS 201-995) on plasma corticotropin
      (ACTH) and corticotropin-releasing hormone (CRH) levels were studied in a patient
      (63-year-old woman) with ectopic ACTH-producing tumors associated with type I
      multiple endocrine neoplasia (MEN-I). The patient had undergone bilateral
      adrenalectomy. Plasma CRH, as well as plasma ACTH, beta-endorphin and alpha-MSH,
      increased. The hormone levels were dramatically decreased by acute administration
      of SMS 201-995. Moderately higher doses of dexamethasone (0.05 or 0.1 mg/kg a
      day) did not decrease plasma CRH or ACTH. An extremely high dose of dexamethasone
      (0.2 mg/kg a day), however, decreased plasma ACTH, but failed to decrease plasma
      CRH. Acute administration of SMS 201-995 further lowered the level of plasma ACTH
      even in this condition. In addition to the decrease in ACTH, SMS 201-995
      decreased plasma CRH. Chronic administration of SMS 201-995 continuously
      decreased plasma CRH, ACTH and beta-endorphin. The decrease in these hormone
      concentrations accompanied the disappearance of hyperpigmentation. These results
      suggested that SMS 201-995 inhibits hypersecretion not only of ACTH but also of
      CRH, and that the agent is therapeutically useful in normalizing the
      hypersecretion of these hormones.

PMID- 1983218
TI  - Hb Hekinan observed in three Chinese from Macau; identification of the GAG----GAT
      mutation in the alpha 1-globin gene.
AB  - Hb Hekinan, an alpha chain variant that is characterized by a Glu----Asp mutation
      at position alpha 27, was observed in three Chinese females attending a prenatal
      clinic in Macau. The relative quantities of the stable hemoglobin were 13-14%
      (average 13.3%); its identification was greatly aided by the separation and
      purification of the peptides by reversed phase high performance liquid
      chromatography. Dot-blot analysis of amplified DNA with 32P-labeled probes
      located the mutation in codon 27 of the minor alpha 1-globin gene; the change
      involved a GAG (coding for glutamic acid) to GAT (coding for aspartic acid)
      mutation.

PMID- 1983219
TI  - Hb K-Ibadan [beta 46(CD5)Gly----Glu] in an Italian family.

PMID- 1983220
TI  - [Multiple endocrine type 2 neoplasia in 3 families].
AB  - In the last 15 years, 29 subjects (13 males, 16 females) aged 8-69 years,
      belonging to 3 kindreds with multiple endocrine neoplasia type 2 (MEN-2) were
      studied with rapid i.v. calcium gluconate infusions (2 mg Ca++/kg in 1 minute) in
      order to detect the presence of medullary thyroid cancer (MTC). Serum samples
      were obtained at 0, 2, 5, 7 and 10 minutes. Calcitonin was measured by
      radioimmunoassay using a commercial kit. On the basis of the results obtained in
      a control group of 28 healthy volunteers, hypercalcitoninemia (HCT) was defined
      as basal and stimulated values above 100 and 200 pg/ml, respectively, in either
      sex. In 2 patients with nodular goiter, HCT correctly predicted the malignant
      nature of the lesions. Out of 22 clinically normal subjects, 3 had HCT: one
      refused consent for surgery, but in the remaining 2 MTC was found, without
      extraglandular extension. Seven patients with surgically proven MTC have been
      followed; 4 have shown HCT: 3 women refused permission for exploratory surgery,
      and a 46 year old male with enlarged lymph nodes in the neck was found to have
      metastatic papillary thyroid cancer. Both calcitonin and thyroglobulin were
      immunohistochemically discovered in metastases and the original thyroid tumor
      (differentiated thyroid cancer, intermediate type). There were 2 false negative
      tests in patients with metastatic disease. This type of biochemical screening in
      members of MEN-2 kindreds allows early detection of MTC and its prevention
      through thyroidectomy in a preneoplastic stage (C-cell hyperplasia).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1983222
TI  - [Diflucan therapy--exchange of clinical experience based on case reports of
      opportunistic mycoses. Bad Neuenahr, 18 August 1990].

PMID- 1983223
TI  - Fetal and neonatal hemopoietic stem cells: considerations in transplantation.

PMID- 1983221
TI  - Pressure responses of hypertensive patients treated with thiazides, beta blockers
      and clonidine during a psychological experimental stress situation.
AB  - A total of 61 hypertensive patients treated during more than six months with
      antihypertensive drugs and showing a satisfactory evolution and normal basal
      arterial pressure values were studied. Patients were subjected to a psychological
      stress test in order to evaluate the effectiveness of the pharmacological
      treatment during and after an emotional situation. Systolic arterial pressure
      (SAP) and diastolic arterial pressure (DAP) were measured in three instances:
      before (I), during (II) and after the test (III). Patients were divided in two
      groups: a) moderate hypertensive subjects (N = 38) treated with thiazides and
      beta-blockers and b) severe hypertensive subjects (N = 23) treated with the same
      drugs plus clonidine. A group of 26 normotensive subjects was used as control.
      Reactivity was determined comparing SAP and DAP values in instances I and II,
      whereas the recovery phase was evaluated by comparing instances I and III. SAP
      and DAP reactivity were highest in severe hypertensive patients and lowest in
      normal subjects. SAP and DAP recovery was partial in severe hypertensive subjects
      and complete in the other two groups. All reactivity and recovery differences
      were statistically significant. These results suggest that antihypertensives
      treatment that normalized basal arterial pressure values in these patients was
      not sufficiently effective to protect them during a psychological stress
      situation.

PMID- 1983224
TI  - Transplantation of umbilical cord blood in Fanconi's anemia.
AB  - It has been shown that human umbilical cord blood contains stem/progenitor cells
      comparable in number to that of adult bone marrow. We report here the first
      successful cases of transplantation of umbilical cord blood cells. The patients
      were suffering from Fanconi's anemia, complicated by severe aplastic anemia.
      During pregnancy, it was shown that the mother was carrying a sibling unaffected
      by the disease and with HLA identical to the patient. Cord blood was collected
      and frozen in liquid nitrogen at birth. After conditioning with low-dose
      cyclophosphamide (20 mg/kg) and thoraco-abdominal irradiation (5 grays), the
      patients received a cord blood transplant of thawed cells. Three patients have
      been transplanted without any immediate side-effect. One has not enough follow
      up, but two patients are alive and well with complete donor hematologic
      reconstitution and no chronic graft versus host disease. Potential developments
      of this technique are an extension of applicability with regard to other diseases
      that might be transplanted and whether such transplants can be performed in
      adults. The relative immaturity of the lymphoid system at birth may be
      advantageous in decreasing the graft versus host reaction if these cells are used
      in a mismatched transplantation. Cord blood cell banks may be useful for
      transplants in patients lacking an HLA-identical donor.

PMID- 1983225
TI  - Collection of placental blood with a view to hemopoietic reconstitution.
AB  - Collection of placental blood in a sterile and closed system is a simple, safe
      and efficient procedure. One hundred and fifty eight units of fetal blood were
      collected by applying the same requirements of quality and safety as those
      defined for blood products in blood banks. No adverse effects were seen in
      mothers or their newborns.

PMID- 1983226
TI  - Hematopoietic stem cell potential from umbilical cord blood.
AB  - We studied the conditions of collection and isolation of hematopoietic cells from
      cord blood in order to optimise the sampling. A statistically significant
      correlation was found between the total stem cell content of the samples and the
      time of delivery suggesting that the quantity of hematopoietic stem cells
      available is higher when cord blood collection is performed earlier during
      pregnancy. Attempt to isolate the white cells resulted in a dramatic loss of stem
      cells. Factors affecting cell recovery and purification must be investigated in
      order to optimize cord blood cell banking.

PMID- 1983227
TI  - In utero transplantation of stem cells in humans.
AB  - Three human fetuses were treated by stem cell transplantation from fetal liver.
      Two of them had severe immunodeficiency disease and the third one had thalassemia
      major. All three in utero transplants were followed by engraftment. No adverse
      effect was seen. The three patients are now born: the first one is cured, the two
      other ones are still under investigation. This procedure, for the first time used
      in humans, is therefore shown to be an effective and safe therapy of inherited
      diseases, during early fetal development.

PMID- 1983229
TI  - Symposium on nucleic acids technology. Nagoya, Japan, November 8-10, 1990.
      Proceedings.

PMID- 1983228
TI  - 5HT3-antagonist receptors: their role in drug-induced emesis.
AB  - Chemotherapy-induced emesis is the most severe side effect in term of patient's
      perception. Current anti-emetic regimen as high dose metoclopramide can achieve a
      complete response in less than 60% of patients. The HT3 receptors appear to be
      the principal mediator of the emetic effect and their blockade have a clear
      activity in the prevention of acute drug-induced emesis, superior to reference
      regimens.

PMID- 1983231
TI  - Treatment of enterocutaneous fistulas with TPN and somatostatin, compared with
      patients who received TPN only.
AB  - Eighteen patients with post-operative enterocutaneous fistulas were treated with
      total parenteral nutrition (TPN), skin care, infection control and intravenous
      somatostatin (SMS) 250 micrograms/h. This group was compared with 30 patients
      treated with standard medical treatment (total parenteral nutrition (TPN), skin
      care and infection control). In the SMS group the fistula output was reduced to
      50% in three days and spontaneous closure was observed in 14 patients after a
      mean of 6.1 +/- 3.1 days of treatment with SMS, and in 18.2 +/- 6.3 days after
      the TPN administration. In the control group the fistula output was reduced by up
      to 50% after a week and spontaneous closure occurred in 20 patients in a mean of
      27.4 +/- 8.7 days after the start of treatment. These results are statistically
      significant. There was one (5.5%) death in the SMS group compared with three
      (10%) deaths in the other, and glucose intolerance was observed in two (11%)
      patients in the SMS group. Somatostatin has been shown to be useful in the
      conservative treatment of enterocutaneous fistulas because of its ability to
      reduce output and accelerate closure.

PMID- 1983232
TI  - Familial bilateral cryptorchidism.

PMID- 1983230
TI  - Transport of L-tyrosine by B16/F10 malignant melanocytes: characterization of the
      process.
AB  - The main characteristics of L-tyrosine (L-Tyr) uptake by B16/F10 malignant
      melanocytes are reported. This amino acid can be taken up by two systems, both of
      them being saturable. The first one would be system L. This system can be studied
      in cells preloaded with amino acids that are a good substrate for system L, such
      as L-methionine or L-tryptophan. The kinetic parameters for L-Tyr uptake by this
      transport system are Vm = 6.5 pmol L-Tyr/10(3) cells.min and Km around 130
      microM. The second system, probably the system ASC, shows lower capacity but
      higher affinity than the former. This system can be detected only in cells
      previously depleted of amino acids, showing approximate kinetic values of Vm 0.05
      pmol L-Tyr/10(3) cells.min and Km around 5 microM. It is shown that the increase
      in cell density yields a decrease in the rate of L-Tyr uptake by system L, but
      this increase does not affect the high affinity system, alpha-MSH does not affect
      significantly the L-Tyr uptake by both systems. 2-Amino bicyclo-(2,2,1)-heptane-2
      carboxylic acid produces a remarkable inhibition of the rate of L-Tyr uptake, but
      alpha-methylaminoisobutyric acid does not affect the rate of transport of this
      amino acid. The absence of sodium produces a slight but reliable decrease in the
      rate of L-Tyr uptake, supporting the involvement of two different transport
      systems. The ionophores monensin and nigericin enhance the transport by system L,
      but this effect is suppressed by the presence of ouabain. This finding indicates
      that the (Na+ -K+)-ATPase is essential for the stimulating action of
      ionophores.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1983233
TI  - Spontaneous perirenal haematoma due to polyarteritis nodosa.
AB  - Polyarteritis nodosa (PAN) is a systemic disease which involves the kidneys in
      70% of cases. We report a case in which the pre-operative diagnosis was perirenal
      abscess or perirenal tumour, but at operation a perirenal haematoma was found.
      After pathological examination, it was recognised as renal involvement with PAN.
      The diagnosis of PAN is often difficult. Renal arterial changes, including
      aneurysm formation, are frequent. Since Kussmaul and Maier first described PAN in
      1866, diagnosis has remained difficult because it is based upon tissue
      examination obtained at biopsy or post-mortem. In this report we present a case
      of renal involvement of PAN resulting in a perirenal haematoma due to spontaneous
      rupture of intrarenal arterial aneurysms.

PMID- 1983234
TI  - DNA prenatal diagnosis.

PMID- 1983235
TI  - The quality of health care. Transactions of the 7th International Congress of the
      International Society for Quality Assurance. Stockholm, Sweden, 17-20 June 1990.

PMID- 1983236
TI  - Quality of medicine.

PMID- 1983237
TI  - Defining quality of care: mission impossible?
AB  - Finding the definition of quality has haunted mankind since the beginning of
      time. As far back as ancient Egypt and classical Greece, descriptions of quality
      show man's struggle with a concept that has not yet ended. Since the beginning of
      this century, descriptions of quality of health care have begun to take form in
      long lists of categories that make up the elements of quality. This catalog
      approach to defining quality has been replaced by the evaluative approach since
      Donabedian's conceptual studies in the 1960s. It has become commonplace now to
      define quality in evaluative terms: by comparing actual care with preset
      criteria, a judgement, and consequently a description or definition, can be
      obtained on real quality of care. In criteria and their derivatives one can
      document his intentions as to good quality; only after measurement and judgement
      can one be certain that quality has been described. A frequent source of concern
      is the erroneous belief that scientific research is synonymous with quality
      assessment. Research results form the basis of criteria for good care, and as
      such contribute to quality, but having obtained good research results does not
      imply that health care is properly and appropriately provided.

PMID- 1983238
TI  - Utilisation of 350 billion SEK in the Swedish public sector.
AB  - Sweden has the largest public sector in the western world. It has been estimated
      that in 1990 public expenditure will amount to 62% of the GNP compared with 43%
      in the OECD countries. Sweden has chosen to allow the public sector, on national,
      regional and local levels, to administer, produce and distribute welfare services
      such as education, child care, the care of the elderly, medical services and
      social insurances. Today it is generally agreed that the public sector cannot
      continue to grow. It has been estimated that total expenditure in the public
      sector in 1990 will amount to 800 billion SEK. Of this amount, transfers, mainly
      social insurances, account for 400 billion SEK, investments for 40 billion SEK
      and consumption for 350 billion SEK.

PMID- 1983239
TI  - Improved utilization of blood due to systematic fractionation.
AB  - The use of human blood has developed from transfusion of whole blood into blood
      component therapy. In addition, plasma has been made available for fractionation
      using large scale, industrial methods. Fortunately enough, all the different
      constituents of the blood are seldom needed in one and the same patient. The
      proper use of human blood becomes an optimization problem with important
      implications for producers as well as users of the products. While the use of red
      cells has ceased to increase, the demand of plasma for production of Factor VIII
      has tended to be enormous. Improved methods, both at the blood bank level and in
      the fractionation process, have become available in recent years, which now tends
      to bring production and demand in harmony. What the impact of recombinant
      technology will be is still unknown. The demand of platelet preparations has
      increased drastically within few years. Here also, important methodological
      developments have appeared giving hope to improve the efficacy of treatment, and
      replacing quantity with quality. Quality assurance in a wide sense plays an
      important role in this process.

PMID- 1983240
TI  - Quality assurance in diagnostic radiology--for its own sake or that of the
      patient.
AB  - X-Ray departments are expensive to equip and run. This paper illustrates how a
      quality assurance programme may help to limit the wastage of resources. The
      production of good quality medical X-ray images is extremely complex and can only
      be guaranteed by implementing some form of quality assurance programme. The
      exposure of patients to X-rays also entails a risk of radiation injury and a
      quality assurance programme is necessary in order to limit this risk to a level
      as low as reasonably practicable. Because of this, in countries within the CEC,
      legislation now requires such a programme to be implemented. The aims of a QA
      programme are defined, and the implications arising from these aims are
      discussed. The role of international organisations in helping to achieve these
      aims is also discussed. The pitfalls of a QA programme in radiology are also
      identified particularly: (1) the tendency to carry out a large programme and
      acquire a considerable amount of data so that the original aims are obscured; (2)
      the possibility of carrying out tests which are expensive to perform and are not
      cost effective and (3) the failure to adapt constantly the content of the QA
      programme to the ever changing needs of the local department and the radiological
      community generally. The various components of a QA programme are presented
      together with illustrations of their possible impact on the standard of work of
      the X-ray department. These include: (1) resource management through film reject
      analysis; (2) patient dose measurements; (3) equipment inspection programme; (4)
      equipment maintenance programme; (5) training and education of staff.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1983241
TI  - The quality of health care: the practical clinical view.
AB  - Quality assurance techniques involving review of charts and performance have been
      pursued for many years. The establishment of conformance standards, as well as
      other aspects of QA considered static and non-dynamic, have been subjected to
      critical analysis by quality workers pursuing a program of total and continuous
      quality improvement. These new concepts have evolved from a study of industrial
      methods which have produced perfect products by a process of progressive
      incremental improvement. The concept of the "bad apple" (which spoils the barrel)
      has been disparaged by the new quality improvement workers. The contention that
      deletion of the "bad apple" is a useless procedure is discussed and refuted. The
      difference between the "rotten apple" (venal or incompetent physician) and the
      "bad apple" (careless or aggressive physician) is cited. The importance of the
      physician in the quality process and failure of the quality literature to get
      physicians involved are discussed. Improvement of physician performance will
      require changes in basic educational training rather than attempting to improve
      current performance by rules and standards. In some countries the problem of poor
      access to the health system by millions of people is at this time a considerably
      greater problem than lack of quality within the health system. This may be an
      area toward which quality workers should direct their attentions.

PMID- 1983242
TI  - Avoidable death as a measure of quality.
AB  - Age standardized mortality rates (SMR) vary between 43 and 162 per 100,000
      inhabitants from cervical cancer in different areas in England, between 19 and
      250 from tuberculosis, between 31 and 249 for asthma, between 0 and 263 from
      rheumatic heart disease, from 0 to 379 for acute respiratory disease, from 18 to
      279 for abdominal hernias, and from 0 to 228 for appendicitis. Essentially
      similar differences were found for some of these diseases between five EEC
      countries. Many differences persist when correlated against social variables, and
      high quality health services should respond to possible differences in incidence.
      Reasons for so-called avoidable mortality vary. In cervical cancer failure to
      include high risk groups in screening programmes or failure to follow up
      screening results have been encountered, in hypertensive disease, failure of
      follow up.

PMID- 1983243
TI  - Perioperative and perinatal death as measures for quality assurance.
AB  - The concept of avoidable death is increasingly used both epidemiologically and
      clinically as an indicator of the quality of health services. This paper examines
      practical experience, particularly in Britain and Europe, of the organisation and
      impact of collaborative mortality studies in improving patient care in surgery
      and perinatal services. It suggests that the technical inadequacies of such
      studies are small compared with their benefits--as long as their message is
      translated into local practice. It offers some key ingredients for effective
      collaborative mortality studies.

PMID- 1983244
TI  - Perioperative risk assessment. The Project Perioperative Risk (PROPER).
AB  - Surgical operations are preceded by an assessment of the anticipated risks for
      the patient due to the operation. The present assessment procedure is not
      optimally organised and the scientific base is weak. In this project a new
      organisation was tested that provides more relevant data on the risk and more
      optimal timing if the risk has to be modified. All elective patients from a
      defined geographical area (n = 1361) were seen one week before the operation for
      risk assessment. They were then followed up during and after the operation. About
      30% of the operations were followed by complications. More than half of them were
      mild. Severe complications were rare. Three risk assessment classifications were
      tested. They were all fairly good estimators of the risk but had different
      properties. The next step in this project is to systematically evaluate the main
      risk-affecting factors to improve the quality of risk assessment.

PMID- 1983246
TI  - A regional computerised surgical audit project.
AB  - This paper describes a computerised surgical audit project which has been
      developed in the North West Thames region of the British National Health Service.
      The need for such a project and the reasons for the approach adopted are
      explained. The key feature is the capacity both for local audit within hospitals
      and for global audit between hospitals. Progress with implementing the project is
      reported. The uses of global audit are described and possible future developments
      outlined.

PMID- 1983245
TI  - Outcome measures of obstetrical and perinatal care.
AB  - Outcome measures of obstetrical and perinatal care may concern the mother or the
      newborn and may involve mortality or morbidity. We reviewed the literature and
      found six outcome measures influenced by the process of care and its
      quality:maternal and perinatal mortalities, postpartum hemorrhage, sequelae of
      obstructed labor, Apgar scores and very early neonatal seizures. Birthweight and
      gestational age at delivery are additional variables to be taken into account as
      major confounding factors in inter-hospital or inter-area comparisons of
      mortality and morbidity. Other potentially useful outcome measures, such as the
      frequency of brachial-plexus palsy and of other birth injuries, need further
      study of their relation to the process of care before being recommended for
      routine use in quality assurance.

PMID- 1983247
TI  - Outcome of blood pressure control.
AB  - Elevated blood pressure (hypertension) is associated with increased risk for
      several complications, and the risk is gradually increasing from the lowest to
      the highest blood pressure levels. Elevated blood pressure is associated with
      metabolic and other abnormalities which are not affected by antihypertensive
      treatment. The majority of cardiovascular complications are found among
      individuals with only moderately elevated blood pressure levels. The
      antihypertensive treatment principles of today are effective against stroke but
      considerably less so against coronary heart disease complications. A programme
      launched by WHO Europe has measured the awareness of hypertension in various
      communities, the adequacy of care, the patients' satisfaction with the care,
      physicians' knowledge and attitudes and the utilization of hypotensive drugs. The
      impact of antihypertensive treatment on stroke and coronary heart disease, which
      latter are the most common, is reviewed. Quality of life effects of blood
      pressure treatment as well as some economic aspects are discussed.

PMID- 1983249
TI  - Quality of management in the health care system.
AB  - Quality of management is a necessary, yet not sufficient, prerequisite in quality
      of care. There are two main approaches to improved quality. One is the
      individualist approach, where the role of the manager is emphasized. The other is
      the contextual approach. Focus is on managerial prerequisites such as
      organizational structure, culture, participation in decision making, and use of
      management time. Individualist as well as contextualist approaches are presented.
      Each decade during the 20th century has had its own "pet theory" regarding what
      problems the manager should allocate time on. A study of 41 Nordic public health
      researchers illustrates that cost-benefit analysis is the best known of ten
      theories. Management ethics, with the manager as ideologist, is seen as
      particularly demanding on managerial creativity.

PMID- 1983250
TI  - Productivity and effectiveness in health care.
AB  - In a series of studies, the Swedish Expert Group on Public Finance (ESO) has
      examined productivity trends in the public sector. Covering some 70% of the
      public sector, the group found an aggregate productivity loss of 1.5% a year from
      1970 to 1980. In the medical services, there was a 3% decline in productivity
      from 1960 to 1980. One implication of the findings is that the growth rate of
      Swedish GNP has probably been overestimated. Determinants of productivity trends
      in the public sector and criticisms levelled at the studies are discussed in the
      paper.

PMID- 1983251
TI  - Introducing quality into cost effectiveness.
AB  - The objective of this study is to explore the problems which can arise when
      quality issues are introduced without proper analysis of the nature and
      objectives of health care. The principles of economics are used to explain why
      the primary output of health care should be perceived in terms of health gained
      (or maintained). Cost Effectiveness Analysis (CEA) is concerned with achieving a
      given output at lowest cost. The problems of measuring and valuing health gains,
      as well as problems arising when a quality dimension is introduced, are discussed
      with reference to the Quality Adjusted Life Year (QALY) as a measure of health
      gain. Quality of service provision is normally achieved at an increased cost per
      QALY. This need not make high quality services inefficient provided care is taken
      in use of terms and Cost Benefit Analysis (CBA) is used to highlight the value
      placed on consumer satisfaction.

PMID- 1983248
TI  - Outcome in vascular surgery.
AB  - In this review of outcome after vascular surgery the results after surgery for
      abdominal aortic aneurysm (AAA), carotid endarterectomy (CEA) and reconstructions
      for ischemia of the lower limbs are discussed and compared with the natural
      course of the disease. Deaths due to rupture of AAA is an increasing problem even
      though elective surgery because of AAA has increased, the appropriateness of CEA,
      which is a seemingly logical operation, has been widely discussed, and operations
      because of ischemia in the lower limbs constitute some 50% of the work of the
      vascular surgeon.

PMID- 1983252
TI  - High technology in health care.
AB  - The structure of the Assistance Publique-Hopitaux de Paris renders necessary an
      inhouse centralized technology assessment unit. This unit, named CEDIT (Committee
      for the Evaluation and the Diffusion of Innovative Technologies), has been
      functioning since 1982 and has advised the Director General on 70 new
      technologies, including the lithotriptor and plasma-exchange therapy. A
      particular feature of the CEDIT is that it is in charge of both the assessment
      and the implementation of the recommendations following this assessment. We
      attempt to describe the consequences of the CEDIT's functioning compared to other
      countries' technology assessment organizations.

PMID- 1983254
TI  - Hospital information systems and quality assurance.
AB  - Hospital information systems may contribute in different ways to quality
      assurance activities such as assessing the quality of primary care, monitoring
      quality indicators, supporting clinical care evaluation studies, and auditing
      concurrently the ongoing process of care using reminders or decision support
      techniques. Examples of effective contributions are given. However, to meet all
      requests of quality assurance in real-world settings many efforts developing new
      technologies will still be necessary.

PMID- 1983253
TI  - Swedish malpractice reports and convictions.
AB  - The Swedish system, with the Board of Health and Welfare as supervisor, and
      Medical Board of Responsibility gives both authorities and patients the
      opportunity to file reports demanding disciplinary action where an error is
      perceived to have been committed. A total of 184 primary care complaints,
      involving 230 staff of which 170 were physicians and 42 nurses, were reviewed.
      Complaints were made by patients or parents in 73% and by the Board of Health in
      14%. Handling took up to 4 years. Erroneous or delayed diagnosis was the cause in
      58%, erroneous medication in 11%, rudeness in 14%. Of the 230 staff reported, 23
      received warnings and 19 reprimands.

PMID- 1983255
TI  - Cost-effectiveness analysis of pharmaceuticals: its informational content and an
      example.
AB  - The importance of cost-effectiveness analysis within the health care sector will
      increase. This is due to changes in the health care sector where there is an
      emphasis on improving the efficiency. The changes will influence the incentive
      structure and, subsequently, the demand for reliable managerial information. Cost
      effectiveness analysis of pharmaceuticals is a good example of the state-of-the
      art of cost-effectiveness applied to health care. A study on the cost
      effectiveness of prophylaxis against infection in total joint replacement is
      presented as an example of an economic evaluation of pharmaceuticals.

PMID- 1983256
TI  - Medical confidentiality.
AB  - The Hippocratic definition of Confidentiality, i.e. the absolute and without any
      exceptions observation of secrecy by the physicians, expresses the Hippocratic
      philosophy in Medicine. Hippocratic Medicine is completely individualized--the
      physician's sole responsibility is the patient's well being. Confidentiality
      undoubtedly strengthens the trust in the patient-physician relationship and
      mutual trust is indispensable for both diagnostic work-up and therapeutic
      applications. Exceptions to confidentiality might be required in order to protect
      the society from infectious communicable disease, from dangerous patients and for
      the scientific progress. However, it is not easy at all to decide for exceptions
      to confidentiality. The profound changes of the human societies in the end of the
      20th century, the fantastic progress in Medicine and Science and the completely
      different approach to the delivery of medical services in modern times, make
      necessary the re-evaluation of medical deontology and medical confidentiality.

PMID- 1983257
TI  - Quality assurance in nursing care: structure and process of nursing care.
AB  - This article has the following objectives: to state the continuity in quality
      assurance in nursing without developing them, to point out the changes and the
      trends, to comment on them and to suggest plans of action. The objectives will be
      attained integrating these changes into the two first steps of the evaluation:
      the elaboration of norms and the measuring, including structure and process and
      mentioning the outcome. Proposals as how to act are presented; different actors
      have to play their own role: the nursing profession, the nursing unit, the
      nursing department, the executive board of hospitals, the legal and
      representative authorities.

PMID- 1983258
TI  - Ethics and the universality of morality.
AB  - Ethics is one of the forces shaping the life of human societies and the ethical
      system contributes to the group's survival and to keep peace and order to satisfy
      social needs. The definitions of ethics, of what is good and what makes an action
      right or wrong, varies widely at different times and at different places.
      However, some basic moral elements are acceptable to most advanced societies.
      Furthermore, many modern scholastic writers defend the absolute universality of
      at least some ethical laws. The limitations of universality survives in war, in
      race discrimination, etc. In modern times, it might be appropriate to search for
      principles for the universality of morality in ecological considerations.
      Progress in ethics is lagging far behind and we must understand now, when the
      complete annihilation of human species is a real possibility, that ethics and
      philosophy are at least as important as science.

PMID- 1983260
TI  - The importance of diagnostic procedures to ensure quality of health care in
      geriatric medicine. Examples from recent studies.
AB  - Within the health care of the elderly with prevention, diagnosis, therapy,
      rehabilitation, nursing care and social service, diagnostic procedures are of
      great importance to avoid under- and over-diagnosis. Many diagnostic difficulties
      exist in elderly patients such as changed reference values, changed normal values
      and changed signs and symptoms. Well-known examples of conditions which are
      likely to be under-diagnosed include depression and urinary incontinence.
      Examples are given from the cardiopulmonary field where e.g. dyspnoea showed to
      be very common, but in only 36% of males and 52% in females related to cardiac
      failure or pulmonary disease. The most common symptom of acute myocardial
      infarction in elderly patients was shown to be dyspnoea, whereas chest pain
      occurred in only one fifth of the cases. In another study of patients with ulcer
      disease loss of appetite and weight, nausea and anemia were more common than
      abdominal pain and heartburn. In peritonitis patients, abdominal pain was
      observed in only just more than half of the cases and guarding and/or abdominal
      rigidity in about one third. In patients with suspect age dementia a detailed
      investigation showed the prevalence of organic dementia to be 89% whereas 3% had
      treatable dementia and 8% non-dementia conditions. In geriatric long-term
      patients the mean hearing loss in the speech area was about 50 dB, in spite of
      the fact that only about 10% of the patients had hearing aids. The need for
      nursing diagnosis is also obvious. It is concluded that a detailed
      multidisciplinary diagnostic investigation procedure is very important in
      geriatric medicine.

PMID- 1983259
TI  - The terminal quality of life and passive or active euthanasia.
AB  - The problems presented by the different categories of dying people are briefly
      discussed from the point of view of terminal quality of life. Euthanasia is used
      in its broader meaning, including both passive and active aspects. Passive
      euthanasia (PE) is exercised by withholding advanced or basic life support
      measures, the commonest form being do not resuscitate orders (DNR). Some data on
      its application are presented. Active euthanasia (AE), which has been proposed
      and being applied to a limited extent lately, is criticized as leading the
      physician and the Society onto risky ground. A position is being taken against
      it. Decision making, examples of guidelines, legal, philosophical and spiritual
      considerations are discussed. Wisdom and loving care should be exercised by the
      physician to assist people in their terminal phases and to alleviate their
      suffering. That there is not a single answer to the problem is discussed.

PMID- 1983261
TI  - Cost-effectiveness of improved housing for the elderly. An example on the use of
      a model to present decision material including effects on quality.
AB  - The Swedish National Audit Bureau has developed a model to present decision
      material in the public sector including effects on quality. In the article the
      model is illustrated with an example that deals with improved housing for elderly
      through installation of elevators in three story houses. The model consists of a
      social cost-benefit analysis and a financial analysis. In this case financial
      analysis is carried out for the owner of the house, the local municipality, the
      county and the central government. A conclusion of the study is that the use of
      social cost-benefit analysis and simultaneous use of financial analysis is
      particularly important, when the focus is on quality. When you have the full
      decision material available you can see from the qualitative factors in the
      social cost-benefit analysis and the lack of qualitative factors in the financial
      analysis why quality so often is forgotten.

PMID- 1983262
TI  - How aging related frailty will influence the quality of care. Results from a 15
      year follow-up of 70-year-old people in Gothenburg, Sweden.
AB  - This report exemplifies how aging in itself, frailty, and morbidity influence
      need of quality of care in the age interval 70-85 according to results obtained
      at the study of representative samples of elderly in Gothenburg, Sweden. A
      significant proportion of the elderly in the age interval 70-79 were lacking
      symptoms due to definable disease, which made possible studies of "normal aging"
      and a differentiation of manifestations of aging from symptoms of disease in the
      elderly. Usage of such knowledge is essential for the improvement of quality of
      care. The trainability of older people was generally good. Much more can be done
      to reactivate the older patient after episodes of acute disease. "Long-term care"
      should be considered as programs differentiated according to the need; shorter
      more active or longer forms of "long-term care." Many frail elderly need longer
      periods of reactivation than available in hospitals. Certain risk factors
      precipitate into functional decline only when we are old. Preventive/postponing
      measures are relevant also for the elderly.

PMID- 1983263
TI  - Elderly people in an orthopedic emergency room--assessment of quality.
AB  - About 25% of all outpatients in the emergency room at the department of
      orthopedics in Malmo are over 70 years of age. Fourteen per cent had no one to
      ask for help at home if needed. Seventy-two per cent understood the information
      given them correctly. About half of the patients reported satisfaction with the
      consultation. Three specific problems related to the service provided were
      identified; a long waiting time, a limited approach to the patients' problem and
      a lack of follow up care.

PMID- 1983264
TI  - Molecular chaperones.

PMID- 1983265
TI  - The molecular chaperone concept.
AB  - Molecular chaperones are a ubiquitous family of cellular proteins which mediate
      the correct folding of other polypeptides, and in some cases their assembly into
      oligomeric structures, but which are not components of those final structures.
      Known chaperones do not possess steric information for protein folding but
      inhibit unproductive folding and assembly pathways which would otherwise act as
      dead-end kinetic traps and produce incorrect structures. Chaperones function by
      binding specifically and non-covalently to interactive protein surfaces that are
      exposed transiently during cellular processes such as protein synthesis, protein
      transport across membranes, DNA synthesis, the recycling of clathrin cages, the
      assembly of organellar complexes from imported subunits, and stress responses.
      This binding is reversed under circumstances which favour correct interactions
      and in some cases ATP hydrolysis is involved in this reversal. Some chaperones
      bind specifically to a structural feature present in a wide range of unrelated
      proteins that is accessible only during the early stages of folding. The nature
      of this structural feature is unknown, but its identification is an important
      goal of current research. Knowledge of chaperone function may be important for
      the production of proteins for biotechnological purposes since in some cases
      chaperones may improve the yield of functional product. It is likely that
      chaperone diseases exist which result from the failure of certain proteins to
      fold correctly due to changes in chaperone structure.

PMID- 1983266
TI  - Nucleoplasmin: the archetypal molecular chaperone.
AB  - Nucleoplasmin was the first protein to be described as a molecular chaperone.
      Studies of nucleoplasmin have resulted in advances in two areas of cell biology.
      Firstly, the pathway of nucleosome assembly in Xenopus oocytes and eggs has been
      elucidated and is the only assembly pathway known in detail. Nucleosome assembly
      represents the major chaperoning function of nucleoplasmin. Secondly,
      nucleoplasmin has been used to elucidate the transport of proteins into the
      nucleus, revealing a selective entry mechanism for nuclear proteins, passage
      through the nuclear pore complex, and a two-step mechanism of transport. The
      properties and functions of nucleoplasmin are reviewed, together with other
      proteins which are related either structurally or functionally to nucleoplasmin.

PMID- 1983267
TI  - The Escherichia coli groE chaperonins.
AB  - The E.coli groES and groEL genes have been shown to form an operon, to be
      essential for E. coli viability, and to belong to the so-called heat-shock class
      of genes whose expression is regulated by the intracellular levels of sigma
      factor sigma 32. Both groE chaperonin proteins possess a seven-fold axis of
      symmetry, groES being composed of seven identical subunits of 97 amino acids
      each, and groEL of fourteen identical subunits of 548 amino acids each. The two
      groE chaperonins interact intimately as judged by both genetic and biochemical
      criteria. This interaction has been shown to be required for both bacteriophage
      morphogenesis and bacterial growth. The groEL chaperonin has been shown to bind
      to a number of incomplete or unfolded polypeptides in vitro. Such binding may
      prevent misfolding and promote rapid intra- or intermolecular folding of
      polypeptides in vivo. The proposed role of the groES chaperonin is to displace
      the polypeptides bound to groEL, thus effectively promoting the recycling of
      groEL.

PMID- 1983268
TI  - Chaperonins and the immune response.
AB  - Chaperonins are a major target of the immune response to bacteria. Infection, or
      immunization, with bacteria induces a strong antibody response to chaperonins,
      and the same proteins also provide a focus for activation of T lymphocyte subsets
      -including CD4, CD8 and gamma-delta T cells. The high degree of sequence
      conservation between prokaryotic and eukaryotic chaperonins makes them candidate
      antigens for models of autoimmunity based on molecular mimicry, and it is
      possible that the immune response to chaperonins has both protective and
      pathogenic potential. The interactions between chaperonins and the immune
      response are reviewed in this article, primarily from the perspective of
      intracellular bacterial infection.

PMID- 1983269
TI  - A mitochondrial chaperonin: genetic, biochemical, and molecular characteristics.
AB  - Mitochondria contain a matrix-localized protein complex composed of subunits
      homologous to the E.coli protein groEL. As with groEL in E.coli, the nuclear gene
      coding for the mitochondrial protein is essential for cell survival and the
      accumulation of the protein is elevated at heat shock-inducing temperatures.
      Biochemical analyses of wild type and mutant yeast strains have shown that this
      protein, hsp60, is required for the correct folding and assembly of newly
      imported, mitochondrially-targeted proteins. There is evidence suggesting a
      mandatory interaction between hsp60 and many imported, as well as mitochondrially
      synthesized, proteins. The implications of these and other data are discussed.

PMID- 1983270
TI  - The plastid chaperonin.
AB  - The discovery and properties of the plastid chaperonin are described. This
      chaperonin is implicated in the folding and assembly of the enzyme ribulose
      bisphosphate carboxylase-oxygenase and in the folding of proteins imported into
      plastids from the cytosol. The plastid chaperonin appears to be unique in that it
      contains two distinct types of 60 kDa polypeptide, whereas only a single subunit
      type has been reported for the bacterial and mitochondrial chaperonins. The
      plastid chaperonin polypeptides are encoded by nuclear genes which are subject to
      complex regulation.

PMID- 1983271
TI  - Role of cytosolic factors in the transport of proteins across membranes.
AB  - In a review article published in 1986 we emphasized that an unfolded conformation
      is a prerequisite for the transport of precursor proteins across membranes, and
      that cytosolic factors exist whose function is to maintain what we termed the
      transport-competent conformation of precursor proteins. Subsequent observations
      in a number of different in vitro systems related both the competent conformation
      and the cytosolic factors to the recent observations on the ATP-requirements for
      protein transport. Here we review the currently available data on such factors,
      and their ATP-requirements, for prokaryotic as well as eukaryotic organisms.
      Furthermore, we discuss possible models for their action and relate them to the
      so-called molecular chaperones. These were originally defined as being involved
      in the proper folding and assembly of oligomeric protein complexes, but have
      since been shown in addition to facilitate the transport of proteins across
      membranes.

PMID- 1983272
TI  - Transport and assembly processes in the endoplasmic reticulum.
AB  - Until recently, the endoplasmic reticulum (ER) of eukaryotic cells was regarded
      as an open corridor for the unregulated movement of newly-synthesized exocytotic
      proteins from their site of membrane translocation to the vesicles that ferry
      them from the transitional elements of the ER to the Golgi apparatus. Moreover,
      it was widely assumed that the folding and assembly of newly translocated
      polypeptides into their tertiary and quaternary structure is a spontaneous
      process that does not involve the intervention of other cellular proteins. In
      this article we review evidence that the ER is a highly discriminatory organelle
      that grants passage only to proteins that have attained an essentially native
      conformation, and summarize current knowledge about resident ER proteins that
      appear to facilitate and/or monitor protein folding and assembly in this
      organelle.

PMID- 1983273
TI  - Symposium on biological models to determine the safety of bound residues in the
      tissues of food-producing animals. October 27-28, 1988, Washington, D.C.

PMID- 1983274
TI  - Biochemical analysis of glycophospholipids from wild-type mouse lymphoma cells
      and from Thy-1 negative mutants which do not add glycolipid-anchored proteins.
AB  - Thy-1 is a major glycophospholipid (GPL)-anchored protein found on the surface of
      neurons, epithelial cells, fibroblasts and murine T-lymphomas. Biochemical
      studies were undertaken to determine if murine T-lymphomas contain glycolipids
      which may be on the path of GPL-anchor biosynthesis. Biosynthetic labeling
      experiments on Thy-1-positive (wild-type) cells followed by battery of chemical
      and enzymatic diagnostics on the isolated [3H]mannolipids have, for the first
      time, led to description of a set of glycolipids which have properties consistent
      with their being GPL-anchor precursors. Using these results as a guide, major
      differences have been observed upon analysis of the radiolabeled mannolipids of
      Thy-1-negative mutants from 7 complementation classes, A-C, E, F, H and I. The
      biosynthetic lesions in anchor synthesis have been identified in some of the
      mutants.

PMID- 1983276
TI  - [Lyme disease (borreliosis): the epidemiological importance of animal vectors and
      reservoirs].

PMID- 1983275
TI  - [The usefulness of flumazenil in benzodiazepine poisoning].

PMID- 1983277
TI  - Role of autonomic nervous system in the response of plasma pancreatic polypeptide
      to glycopenia in dogs.
AB  - The effect of cholinergic and adrenergic influences on pancreatic polypeptide
      (PP) release was studied in dogs. Administration of acetylcholine resulted in an
      elevation of plasma PP, whereas epinephrine induced no increase. Insulin-induced
      hypoglycemia increased plasma PP in a conscious state but not in anesthetized
      dogs. The infusion of phentolamine or propranolol did not affect the response of
      plasma PP to insulin-induced hypoglycemia, whereas atropine markedly inhibited
      the increase in plasma PP. Likewise, atropine reduced the rise of plasma PP
      during the intravenous administration of 2-deoxy-D-glucose (2-DG). We conclude
      from the present experiments that cholinergic mechanisms are of major importance
      in the response of PP to insulin- and 2-DG-induced glucoprivation, while the
      major role of the adrenergic mechanism was not proved.

PMID- 1983278
TI  - Proceedings of the Sixth International Congress on Twin Studies. Rome, 28-31
      August 1989.

PMID- 1983279
TI  - Variable number of tandem repeats in zygosity diagnosis in twins.
AB  - The use of DNA restriction fragment length polymorphisms (RFLP) to analyze
      variable number of tandem repeat (VNTR) sequences dispersed in the human genome,
      has become a powerful tool for the study of population genetics due to the very
      substantial polymorphism involved. Because the markers usually employed for twin
      zygosity determination (such as sex combination, placentation, HLA typing, blood
      group antigens, etc) may not be uniformly informative, we propose the use of
      synthetic olygonucleotides, representing VNTR "core" sequences, for the
      determination of zygosity in twins.

PMID- 1983280
TI  - International Scientific Symposium on Fibrinogen, Thrombosis, Coagulation, and
      Fibrinolysis. August 30-September 1, 1989, Taipei, Taiwan, Republic of China.

PMID- 1983281
TI  - Lasers in medicine.
AB  - Since its discovery, the laser has been intensively investigated and used in
      medicine, first in ophthalmology then in ear, nose and throat surgery,
      gynaecology, neurosurgery etc. Development spans from the ruby and argon lasers
      in outpatient eye surgery to the carbon dioxide and Nd:YAG lasers in the
      operating theatres and further on to the PDT-dye lasers, excimer and solid state
      angioplasty lasers or flash lamp pumped "gallstone cracker" lasers. The CO2-Nd:
      YAG laser combination will be described as the state-of-art surgical laser. This
      simultaneous, coaxial and coherent combination laser offers a new possibility to
      cut and coagulate effectively at the same time. Operating times are shortened and
      bleeding volumes minimised. The CO2-Nd: YAG laser represents a new type of
      interaction between laser and tissue, laser enhanced tissue absorption, which
      will be described.

PMID- 1983282
TI  - The development of a laser for stone fragmentation and its place in the
      management of stones in the era of extracorporeal lithotripsy.
AB  - The parameters of a laser which govern stone fragmentation are the pulse
      duration, wavelength and fibre diameter. The pulse duration is the most important
      parameter governing fibre transmission. The shorter the pulse duration the less
      tissue damage and the easier the plasma production at the stone surface but the
      greater the difficulty to transmit the laser energy through the fibre. At 1
      microsecond pulse duration the laser wavelength is highly significant because it
      governs the degree of absorption at the stone surface necessary for plasma
      production. Transmission of this laser energy through 200 micron core fibres is
      straightforward. Fragmentation is achieved by placing the fibre in contact with
      the stone surface. There is negligible tissue injury. A miniaturised ureteroscope
      has been developed specifically for the laser. This appears to be easier to use
      and carries less risk of instrumentational injury to the ureter.

PMID- 1983283
TI  - Mechanisms of altered hormone-neurotransmitter action during aging: from
      receptors to calcium mobilization.

PMID- 1983284
TI  - The immune response to mycobacterial heat shock proteins.
AB  - Several prominent protein antigens involved in antibody and T cell responses to
      mycobacteria have been identified as members of highly conserved heat shock
      protein families. The immunogenicity of heat shock proteins in a broad range of
      infections, along with the extensive sequence identity between corresponding host
      and pathogen homologues, and the potential for localized accumulation in response
      to stress stimuli, makes these antigens attractive candidates for theories of
      autoimmunity based on "molecular mimicry". The 65 kilodalton (kD) heat shock
      protein of mycobacteria has indeed been shown to modulate the course of
      autoimmune disease in experimental animals, and immune responses to this and
      other heat shock proteins have been demonstrated in association with human
      autoimmune diseases. This paper provides a brief review of the immune response to
      mycobacterial heat shock proteins during infection and autoimmunity.

PMID- 1983285
TI  - The inactivation of sodium channels in the node of Ranvier and its chemical
      modification.
AB  - The many experimental studies reported demonstrate the complexity of what is
      termed inactivation, the decrease of current flow through sodium channels at
      maintained depolarization. Even at the normal resting potential of, say, -70 mV
      for a frog node of Ranvier, ca. 20% of the channels are closed and inactivated,
      i.e., incapable of passing current on a sudden depolarization, in contrast to the
      remaining 80% of closed but resting channels. The term inactivation has thus
      evolved from bulk current ("macroscopic") phenomena and is applied to channels
      although its single-channel ("microscopic") basis is not entirely clear and may
      even vary among preparations. It is conceivable that the macroscopic phenomenon
      may have more than a single microscopic cause; this point will probably not be
      settled until a physical description of the conformational states of the channel
      macromolecule becomes available. At any rate, channel transition into an
      inactivated closed state can be easily affected by numerous reagents of highly
      diverse chemical nature and, most likely, different primary sites of action as
      already suggested by the sidedness of effective application, e.g., iodate and
      endopeptidases to the inside, polypeptide toxins to the outside. But also the
      search for a common denominator, a secondary target of all these treatments, has
      not been very successful as demonstrated by the experiments with group-specific
      reagents. Since modification of inactivation is often accompanied by shifts in
      the voltage dependence of gating parameters, a target could be the "voltage
      sensor" of the channel, charged and/or dipolar components of the channel
      macromolecule that, by being moved in the electric field, somehow induce gating
      and whose movement is measured as gating current (e.g, Hille, 1984). The fraction
      of open channels as a function of membrane potential, F(E), may serve as an
      indicator. It may be simply shifted (to more negative potentials) as by
      veratridine (Leibowitz et al., 1987) or flattened (reduction of gating charge?)
      and shifted (in the positive direction) as by Anemonia sulcata toxin II (Ulbricht
      and Schmidtmayer, 1981) or chloramine-T (Drews, 1987). On the other hand, the
      steady-state inactivation curve is shifted to more negative potentials by the
      toxin (Ulbricht and Schmidtmayer, 1981), but to more positive potentials by
      chloramine-T (Wang, 1984a; Schmidtmayer, 1985). Obviously, modifiers may affect
      activation and inactivation quite differently, a result that touches on the
      question as to what extent inactivation derives its potential dependence from
      activation.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1983287
TI  - Restriction fragment length polymorphism segregation analysis of the Li locus in
      Trifolium repens L.
AB  - The Li locus in white clover controls the presence of cyanogenic beta-glucosidase
      (linamarase) activity in leaf tissue, such that plants homozygous for the 'null'
      allele (li) have no linamarase activity in this tissue. The isolation of a cDNA
      clone from linamarase mRNA is described. The cDNA clone is used to further
      characterise alleles of the Li locus. Northern blot analysis shows that plants
      homozygous for the 'null' allele (li li) produce very reduced levels of mRNA
      which hybridises to the cDNA. Heterozygous plants (Li li), which have
      intermediate levels of enzyme activity, produce intermediate levels of mRNA.
      Southern blot analysis of Hind III digested genomic DNA shows that the white
      clover genome contains three genes with homology to the linamarase cDNA and that
      at least two of these genes segregate independently. Analysis of the
      cosegregation of linamarase activity and the presence of genomic restriction
      fragments identifies the genomic sequence specifying linamarase structure and
      indicates either a structural or cis acting control function of the Li locus.

PMID- 1983286
TI  - Molecular analysis of barley mutants deficient in chloroplast glutamine
      synthetase.
AB  - A barley leaf cDNA library has been screened with two oligonucleotide probes
      designed to hybridize to conserved sequences in glutamine synthetase (GS) genes
      from higher plants. Two GS cDNA clones were identified as hybridizing strongly to
      one or both probes. The larger clone (pcHvGS6) contained a 1.6 kb insert which
      was shown by primer extension analysis to be an almost full-length cDNA. Both
      clones were more closely related to cDNAs for the chloroplast form of GS (GS2)
      from pea and Phaseolus vulgaris than to cDNAs for the cytosolic form (GS1). A
      sequence identical to an N-terminal sequence determined from a purified
      preparation of the mature GS2 polypeptide (NH2-XLGPETTGVIQRMQQ) was found in the
      pcHvGS6-encoded polypeptide at residues 46-61, indicating a pre-sequence of at
      least 45 amino acids. The pre-sequence has only limited sequence homology to the
      pre-sequences of pea and P. vulgaris GS2 subunits, but is similarly rich in basic
      residues and possesses some of the structural features common to the targeting
      sequences of other chloroplast proteins. The molecular lesions responsible for
      the GS2-deficient phenotypes of eight photorespiratory mutants of barley were
      investigated using a gene-specific probe from pcHvGS6 to assay for GS2 mRNA, and
      an anti-GS antiserum to assay for GS2 protein. Three classes of mutants were
      identified: class I, in which absence of cross-reacting material was correlated
      with low or undetectable levels of GS2 mRNA; class II, which had normal or
      increased levels of GS2 mRNA but very little GS2 protein; and class III, which
      had significant amounts of GS2 protein but little or no GS2 activity.

PMID- 1983288
TI  - Expression of glutamine synthetase genes in roots and nodules of Phaseolus
      vulgaris following changes in the ammonium supply and infection with various
      Rhizobium mutants.
AB  - In this paper we have examined whether the four glutamine synthetase (gln) genes,
      expressed in roots and nodules of Phaseolus vulgaris are substrate-inducible by
      ammonium. Manipulation of the ammonium pool in roots, through addition and
      removal of exogenous ammonium, did not elicit any changes in the abundances of
      the four mRNAs thus suggesting that the gln genes in roots of this legume are
      neither substrate-inducible by ammonium nor derepressed during nitrogen
      starvation. In nodules the effect of the ammonium supply on expression of the gln
      genes has been examined by growing nodules under argon/oxygen atmospheres, or
      with a number of Fix- Rhizobium mutants, and following addition of exogenous
      ammonium. The results of these experiments suggest that the expression of the gln
      gamma gene, which is strongly induced during nodule development, is primarily
      under a developmental control. However nitrogen fixation appears to have a
      quantitative effect on expression of gln-gamma as the abundance of this mRNA is
      about 2 to 4-fold higher under nitrogen-fixing conditions. This effect could not
      be mimicked by addition of exogenous ammonium and moreover is not specific to the
      gln-gamma gene as mRNA from a leghaemoglobin gene was similarly affected. Taken
      together these results have failed to find an effect of ammonium on specifically
      inducing the expression of glutamine synthetase genes in roots and nodules of P.
      vulgaris.

PMID- 1983289
TI  - A copia-like element in Pisum demonstrates the uses of dispersed repeated
      sequences in genetic analysis.
AB  - A DNA sequence between two legumin genes in Pisum is a member of the copia-like
      class of retrotransposons and represents one member of a polymorphic and
      heterogeneous dispersed repeated sequence family in Pisum. This sequence can be
      exploited in genetic studies either by RFLP analysis where several markers can be
      scored together, or the segregation of individual elements can be followed after
      PCR amplification of specific members.

PMID- 1983291
TI  - Involvement of transmitter mechanisms in the behavioural effects of angiotensin
      II.
AB  - The behavioural effects of angiotensin II (AT II) were studied using the
      following paradigms: seizures (threshold and intensity) in mice; active avoidance
      (shuttle-box) in rats; passive avoidance (step through) in rats; exploratory
      activity (open field) in rats; apomorphine stereotypy in rats. The involvement of
      DA- and GABA-ergic transmitter mechanisms in the effects of AT II was also
      studied. It was found that AT II increased the seizure threshold and decreased
      the seizure intensity, the effects being potentiated by DA- and GABA-ergic
      agonists and prevented by DA- and GABA-ergic antagonists. AT II effect on seizure
      threshold was stronger when AT II was applied after withdrawal of repeatedly
      injected DA-ergic antagonist pimozide. AT II improved retention in active and
      passive avoidance tasks. This effect was potentiated by DA- and GABA-ergic
      agonists. Postrial saralasin and haloperidol abolished the retention-facilitating
      effect of AT II. Bicuculline and picrotoxin abolished the influence of GABAA
      ergic agonists on the memory effect of AT II. AT II changed exploratory behaviour
      in a nonlinear dose-effect manner. The stimulant effects of AT II were
      antagonized by saralasin, increased by apomorphine and nomifensine and decreased
      by haloperidol and alpha-methyl-para-tyrosine (alpha MpT). AT II enhanced
      apomorphine stereotypy; the effect was decreased by saralasin and alpha MpT, and
      abolished by haloperidol. These results suggest that the behavioural effects of
      AT II are mediated by interactions with brain AT II receptors. DA and GABA
      receptors modulate in some way the AT II activity.

PMID- 1983290
TI  - Involvement of neurotransmitter and neuropeptides in behavioural action of some
      neurohormones.
AB  - Investigations were made of the action of ACTH and LH-RH on a number of
      behavioural paradigms and the possible involvement of neurotransmitters or
      opiates by pretreatment of receptor blockers in rats and mice. ACTH delayed the
      extinction of active avoidance behaviour. Atropine and haloperidol blocked this
      action, whereas phenoxybenzamine and propranolol were ineffective. LH-RH or a
      highly potent analogue of LH-RH (D-Trp6-LH-RH) decreased the rate of
      disappearance of dopamine in the hypothalamus following alpha-methyl-
      paratyrosine inhibition of catecholamine synthesis, and blocked the accumulation
      of serotonin following MAO inhibition. LH-RH or the analogue attenuated the
      consolidation of passive avoidance learning. Apomorphine-induced cage-climbing
      was also inhibited by the LH-RH analogue, but this action was not influenced by
      naloxone. Open-field activity (ambulation, rearing and grooming) was decreased by
      the analogue peptide. Naloxone blocked the action on ambulation and rearing, but
      was ineffective on grooming. The LH-RH analogue caused a dose-dependent increase
      in cataleptogenic activity. This action could not be blocked with naloxone. The
      LH-RH analogue suppressed picrotoxin-induced seizures. Naloxone restored the
      situation to the control level. The data suggested that the effects of some
      neurohormones are mediated by transmitters or endogenous opiates, and that both
      peptide-transmitter and peptide-peptide interactions have to be considered in the
      action of neurohormones.

PMID- 1983293
TI  - The effect of histamine receptor antagonists on immunosuppression induced by the
      cis-isomer of urocanic acid.
AB  - Urocanic acid (UCA) is found in the stratum corneum predominantly as the trans
      isomer; on ultraviolet B (UVB) irradiation, isomerization to the cis-isomer
      occurs. Cis-UCA has been shown to mimic the consequences of UVB irradiation in
      generating transient suppression of contact and delayed hypersensitivity (DH)
      responses. In an attempt to elucidate the mechanisms of action of UCA, the
      effects of 2 histamine receptor antagonists, cimetidine and terfenadine, were
      examined. One day after skin painting murine ears with cis-UCA, the number of
      ATPase- cells was reduced from 1068 to 408 mm-2. However, if cimetidine or
      terfenadine was applied at the same time as cis-UCA, the number of ATPase- cells
      was reduced only slightly from the control value, to 1028 and 892 respectively.
      Cis-UCA given subcutaneously or epidermally 5 h before infection of mice with
      herpes simplex virus suppressed the DH response on subsequent challenge with the
      virus. If cimetidine or terfenadine was added at the same time as cis-UCA, little
      suppression of the DH response to the virus occurred. Thus 2 effects of cis-UCA,
      on the number of ATPase+ epidermal cells and on DH response, were reduced or
      abrogated by histamine receptor antagonists, which may indicate that cis-UCA acts
      through histamine-like receptors in the skin.

PMID- 1983292
TI  - Effects of polyamines on synaptic transmission, with special attention to the
      glutamatergic system.
AB  - Effects of synthetic philanthotoxin-4.3.3 (PTX-4.3.3) and of its eleven
      structural analogues on glutamatergic transmission in the insect muscle,
      nicotinic transmission in the insect CNS and glutamatergic transmission in the
      mammalian CNS, are described. Compared with the insect muscle, the insect CNS is
      about 100 times less sensitive for most of these toxins and the mammalian CNS
      about 1000 times less reactive. In general, the relative activities of the
      analogues are comparable except for one toxin: dideaza-PTX-12, which is hardly
      active in insects and is the most active blocker of synaptic transmission from
      the Schaffer collaterals to pyramidal cells in the rat hippocampal slices.
      Dideaza-PTX-12 is also the most active inhibitor of glutamate uptake. It is
      concluded that the latter compound may be a prototype of a new class of
      neuroactive drugs affecting the glutamatergic transmission in the mammalian CNS.

PMID- 1983294
TI  - Effect of HLA-DR/RFLP matching in complicated corneal transplantations.
AB  - Fifty-one elective high-risk transplantations were matched according to HLA/DR
      antigens and RFLP-subtypes. The 18-month survival of the grafts was 93% in the
      matched group compared to 50% in a nonmatched-compatible historical control
      group.

PMID- 1983295
TI  - [Mixed hepatopathy due to parenteral gold salts].
AB  - A case of a patient with rheumatoid arthritis (RA) of long evolution associated
      to dry syndrome, who developed a dissociated cholestasis after parenteral
      administration of gold salts, is suppression of gold salts. We comment on the
      clinical, biochemical, and histological features of intrahepatic cholestasis
      related to gold salts, as well as the evolution and the necessary criteria in
      order to make the diagnosis. We highlight the normal level of bilirubin,
      comparing it to that described in the literature.

PMID- 1983296
TI  - Mitogenic activity of natural and synthetic lignins against cultured splenocytes.
AB  - Various natural lignified materials and synthetic dehydrogenation polymers (the
      so-called synthetic lignins) prepared from several phenylpropenoids were
      investigated for their mitogenic activity. All of these materials time- and dose
      dependently stimulated the DNA synthesis of isolated mouse splenocytes. However,
      their stimulating activity was significantly decreased when the splenocytes were
      pretreated with anti-Thy-1.2 monoclonal antibody and rabbit complement. Natural
      and synthetic lignins demand attention as potential immunopotentiators.

PMID- 1983297
TI  - A cDNA sequence coding for glutamine synthetase in Hordeum vulgare L.

PMID- 1983298
TI  - The DNA sequence and structural organization of the GC2 plasmid from the red alga
      Gracilaria chilensis.
AB  - The complete DNA sequence of the circular GC2 plasmid from the red alga
      Gracilaria chilensis was obtained. It contains 3827 bp and has a base composition
      of 75% A + T nucleotides. The sequence revealed that GC2 has two inverted
      repeats, each of 290 nucleotides, that border four long direct tandem repeats of
      216 nucleotides. five short, direct, tandem repeats of 21-22 nucleotides were
      also found in the plasmid. The plasmid sequence has one major open reading frame
      that could encode a 411 amino acid polypeptide. Finally, the GC2 plasmid is
      transcriptionally active.

PMID- 1983299
TI  - Chloroplast DNA variability in the genus Helianthus: restriction analysis and S1
      nuclease mapping of DNA-DNA heteroduplexes.
AB  - Chloroplast DNA (cpDNA) from 36 wild species of the genus Helianthus has been
      analysed with three restriction endonucleases (Bam HI, Hind III and Sst I). Out
      of the 71 restriction sites described on the reference cpDNA (sunflower cpDNA),
      three insertions/deletions and seven site modifications were detected during the
      survey of the other cpDNAs. Since restriction mapping showed only a very limited
      fraction of the DNA variability, we chose to adapt the S1 nuclease mapping
      technique to detect fine variations between chloroplast genomes. For this
      purpose, DNA-DNA heteroduplexes obtained between sunflower and wild-species DNAs
      were digested by S1 nuclease and the resulting mismatches were detected by
      classical endonuclease restriction and hybridization methods. The S1 nuclease
      mapping results were confirmed by sequencing one S1 nuclease-sensitive region
      detected between cultivated sunflower and two perennial wild-type species. As a
      result of these analyses, it appeared that the combination of restriction mapping
      and S1 nuclease mapping might be helpful to differentiate taxonomically close
      cytoplasms.

PMID- 1983300
TI  - Phytochrome-mediated activation of the gene for cytosolic glutamine-synthetase
      (GS1) during imbibition of photosensitive lettuce seeds.
AB  - A full-length cDNA encoding glutamine synthetase was isolated from a lambda gt11
      library constructed from the poly(A)+ RNA isolated from lettuce seeds incubated
      under red light. The nucleotide sequence of the cDNA and the deduced sequence of
      amino acids showed a high degree of homology to those of the cytosol-type
      glutamine synthetase from other plants. Northern and dot-blot analyses of
      poly(A)+ RNA extracted from the seeds incubated under various light conditions
      showed that the activation of the gene for cytosolic glutamine-synthetase during
      imbibition of lettuce seeds is directly or indirectly regulated by phytochrome.

PMID- 1983301
TI  - RFLP mapping of the abp1 locus in maize (Zea mays L.).

PMID- 1983302
TI  - Targeting of glutamine synthetase to the mitochondria of transgenic tobacco.
AB  - Two transgenic tobacco lines were genetically engineered to contain chimaeric
      genes encoding the glutamine synthetase (GS) gamma polypeptide of Phaseolus
      vulgaris (French bean), expressed from the cauliflower mosaic virus 35S promoter.
      One (MIT-1) contained two copies of a construct including the first 60 amino
      acids of the Nicotiana plumbaginifolia beta-F1 ATPase to target the GS
      polypeptide to the mitochondrion. The other (CYT-4) contained a single copy of a
      cytosolic GS construct. Leaves of in vitro plantlets expressed the constructs and
      contained a novel GS polypeptide, which assembled into active GS isoenzymes
      constituting about 25% of the total GS activity. In in vitro plantlets of MIT-1,
      but not CYT-4, the novel polypeptide was found to be associated with the
      mitochondria. Moreover in MIT-1, the size of the novel polypeptide was not that
      predicted of the precursor (44.9 kDa) but was about 39 kDa, the same size as the
      authentic GS gamma polypeptide in CYT-4. These results are consistent with the
      precursor being imported into the mitochondria and cleaved near the fusion
      junction between the two sequences. These experiments have therefore shown that
      the presequence of the beta-F1 ATPase has successfully targeted the GS gamma
      polypeptide to the mitochondria of transgenic tobacco where it has assembled into
      an active isoenzyme. However, in fully regenerated plants growing
      photoautotrophically in growth-room conditions, although the constructs were
      still expressed, the gamma polypeptide did not accumulate to the same levels as
      in in vitro plantlets and new isoenzyme activities were now barely detectable.
      Moreover in leaves of the mature MIT-1 plants, the gamma polypeptide was found to
      be associated with the insoluble fraction of the mitochondria. The results of
      these experiments are discussed.

PMID- 1983303
TI  - Association between microtubules and Golgi vesicles isolated from rat parotid
      glands.
AB  - We report an isolation procedure of trans-Golgi vesicles (GVs) from rat parotid
      glands. Various organelle markers were used, particularly galactosyl transferase
      as a trans-Golgi marker, to test the purity of the GV fraction. A quantitative in
      vitro binding assay between microtubules and GVs is described. The vesicles were
      incubated with taxol-induced microtubules, layered between 50% and 43% sucrose
      cushions and subjected to centrifugation. Unlike free microtubules which were
      sedimented, the GV-bound microtubules co-migrated upward with GVs. Quantification
      of these bound microtubules was carried out by densitometric scanning of
      Coomassie blue-stained gels. The association between microtubules and GVs
      followed a saturation curve, with a plateau value of 20 micrograms of microtubule
      protein bound to 500 micrograms of GV fraction. The half-saturation of the GV
      sites was obtained with a microtubule concentration of 20 micrograms/ml. Electron
      microscopy of negatively stained re-floated material showed numerous microtubule
      vesicle complexes. Coating of microtubules with an excess of brain microtubule
      associated proteins (MAPs) abolished binding. In the absence of exogenous
      microtubules, we showed that the GV fraction was already interacting with a class
      of endogenous rat parotid microtubules. This class of colcemid and cold-stable
      microtubules represents 10-20% of the total tubulin content of the parotid cell.

PMID- 1983304
TI  - [Mononucleosis syndromes].

PMID- 1983306
TI  - [Effect of a derivative of 1,5 benzodiazepine on sleep].
AB  - The object of this investigation was to study the effect of a benzodiazepine upon
      the cycle wakefulness-sleep. Wistar rats received 0.9 mg/kg of the chlorate
      derivative of beta lactam 1.5 benzodiazepine intraperitoneally and the action was
      analyzed by means of continuous polygraphic registers for ten hours long. Results
      indicate that this substance decreases wakefulness and slightly increases slow
      wave sleep. Paradoxical sleep increases significantly (p less than 0.05). Latency
      of the first phase of paradoxical sleep decreases considerably. These effects
      suggest that this compound favors sleep under present experimental conditions.

PMID- 1983305
TI  - [Causes and medical effects of cocaine abuse].
AB  - Historical data concerning the use of cocaine, its epidemiology, chemistry and
      pharmacology, as well as its medical complications and treatment, in both acute
      intoxication and chronic addiction is reported. Its repercussion and damage upon
      the nervous system with neurologic and psychiatric alterations is also reported.
      The frequency of cerebral hemorrhages and myocardial, and other visceral,
      infarctions due to vascular lesions are discussed. Various pulmonary lesions
      produced by the different routes used and the multiple obstetric problems during
      pregnancy, such as abnormal labour with products showing cerebral damage and
      teratogenic lesions due to the use of cocaine are presented. Lastly, the present
      prophylactic campaigns against the use of cocaine and other drugs is mentioned.

PMID- 1983307
TI  - [Poisoning caused by neuroleptics and other related drugs].
AB  - Neuroleptics (phenothiazines) and related medicaments such as haloperidol and
      metoclopramide, are frequent cause of intoxication. The main manifestations are
      extrapyramidal symptoms. In most cases the intoxications have an acute evolution
      and the large doses may be complicated with shock, coma and ventricular
      fibrillation; persistent hyperthermia brings poor prognosis. Their chronic use,
      even at therapeutic doses, may produce late dyskinesia, difficult to manage.
      Diphenhydramine is particularly useful to treat the acute intoxication; this
      could be started with slowly intravenous injected 1 mg/kg until symptoms
      disappear, and then continue per os for a minimum of these drugs. Its improper
      use and abuse are due to therapeutic mode.

PMID- 1983308
TI  - [Consequences of the mechanization of medicine].

PMID- 1983309
TI  - Galactopoietic and mammogenic effects of long-term treatment with bovine growth
      hormone and thrice daily milking in goats.
AB  - Starting in mid-lactation, goats were treated daily for 22 weeks with 0.15 mg
      recombinant bovine GH (bGH)/kg, or an equivalent volume of vehicle. One gland of
      each goat was milked thrice daily throughout treatment, the other twice daily.
      Mammary differentiation was studied in biopsy samples obtained before treatment
      and after 3 and 22 weeks of treatment, by determination of in-vitro synthesis
      rates of milk constituents and measurement of enzyme activities. Mammary growth
      was measured using a whole-body imaging technique (magnetic resonance imaging;
      MRI). bGH caused an immediate and sustained increase in milk yield of
      approximately 23% overall, whilst the glands milked thrice daily produced
      approximately 14% more than the control glands milked twice daily. The effects of
      the combined treatment were additive, but not synergistic. A synergistic effect
      of the combined treatment resulted in a significant improvement in lactation
      persistency. A stimulatory effect of milking frequency on mammary enzyme
      activities was evident only in bGH-treated goats at 3 weeks, but in both groups
      at 22 weeks. Synthesis rates of casein and lactose were increased at 3 weeks only
      by the combined treatment. Thus bGH accelerated or augmented the differentiative
      response to thrice daily milking. Mammary parenchyma volume, estimated by MRI,
      increased significantly during the first 12 weeks of bGH treatment and remained
      higher throughout the rest of the treatment period. Cell number was estimated
      from parenchyma volume and DNA concentration; this decreased significantly in the
      controls between weeks 1 and 22, but remained constant in the bGH group. In nine
      of the ten goats, parenchyma volume and cell number increased in the gland milked
      thrice daily relative to the control gland milked twice daily during the course
      of the experiment. Thus bGH stimulated growth of the mammary gland over and above
      that induced by the frequent milking. The absence of any detectable increase in
      thymidine incorporation suggests that this growth consisted of cellular
      hypertrophy rather than hyperplasia.

PMID- 1983310
TI  - Growth hormone (GH) secretion in the dwarf rat: release, clearance and
      responsiveness to GH-releasing factor and somatostatin.
AB  - The new mutant GH-deficient dwarf (Dw) rat was used to study the effects of GH
      releasing factor (GRF) or somatostatin (SRIF) on GH release. In anaesthetized
      adult Dw female rats, i.v. injections of GRF (0.031-2.0 micrograms) elicited a
      dose-dependent release of GH. Although the peak plasma GH responses to maximal
      GRF doses were much lower in adult Dw rats compared with normal rats of this
      strain (AS), the responses largely reflected their relative pituitary GH contents
      (140 +/- 17 micrograms vs 2.9 +/- 0.4 micrograms, AS vs Dw (means +/- S.E.M.), P
      less than 0.001). Except at 20 days of age, normal AS rats were more sensitive to
      GRF than Dw rats despite their larger body weight. Peak GH responses to injection
      of 31.25 ng GRF increased nine-fold in normal rats between 20 and 40 days,
      whereas the GH responses to this GRF dose diminished in Dw rats over this age
      range, and their pituitary GH content was only 2-5% of that of age-matched AS
      rats. Treatment with human GH (200 micrograms/day for 7 days) stimulated growth
      in 40-day-old Dw rats and slightly increased the GH response to a low dose of
      GRF. Basal GH levels in adult Dw animals were sevenfold lower than in AS rats
      (2.4 +/- 0.3 vs 17.6 +/- 3.3 micrograms/l P less than 0.001) and were further
      suppressed by i.v. infusion of SRIF (25 micrograms/h). As in normal rats, a
      rebound GH secretion occurred in Dw rats after stopping SRIF, which was blocked
      by injection of anti-GRF serum.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1983311
TI  - Treatment and monitoring of systemic vasculitis.

PMID- 1983312
TI  - International symposium on cirrhosis, hepatic encephalopathy and ammonium
      toxicity. Valencia, Spain, November 27-29, 1989. Proceedings.

PMID- 1983313
TI  - Cortisol elevation and serum gamma-glutamyl transpeptidase in response to adverse
      job conditions: how are they interrelated?
AB  - This study explores the use of plasma cortisol as an indicator of psychologically
      straining work. As plasma cortisol and liver function might be associated through
      biological mechanisms, this paper has a secondary object, namely to explore the
      interaction between cortisol and liver function. As an index of liver function
      the serum level of gamma-glutamyl transpeptidase (GT) was used. The study sample
      was 2,000 prison employees from 67 different prisons in Sweden. Questionnaires
      and health examinations were used as well as measurements of plasma cortisol and
      serum GT. Very few work-related factors were associated with plasma cortisol
      unless analyzed separately for high and low level of serum GT. Two-way analyses
      of variance showed significant differences in the physiological "responses" to
      straining work with regard to psychic strain at work (men), social support at
      work (men), job role (men), loneliness at work (men and women), management style
      (women) and overtime work (women) between "low serum GT" and "high serum GT"
      individuals. Aggregated analyses showed that prison means of work-related factors
      were in some respects associated with prison means of plasma cortisol. The
      conclusion is that in individually based analyses plasma cortisol is difficult to
      use as an indicator of straining work, especially if the level of serum GT is
      unknown.

PMID- 1983314
TI  - Molecular nature of mutations causing beta zero-thalassaemia in Azerbaijan.
AB  - Beta zero-thalassaemia comprises a series of closely related haemoglobinopathies
      which are widely spread in some areas (the Mediterranean, Caucasus, Central Asia,
      and others). It is caused by a variety of mutations in the beta-globin gene which
      damage its expression, thus leading to severe illness, which is often lethal at
      an early age. By means of the polymerase chain reaction (PCR), restriction
      analysis, and sequencing by the Maxam-Gilbert method, we have identified a number
      of mutations in the beta-globin gene that cause beta zero-thalassaemia in the
      Azerbaijanian population, viz AA deletion in codon 8, C----T transition in codon
      39, and a previously unknown G deletion in codons 82/83.

PMID- 1983315
TI  - The origins of cell diversity in the insect central nervous system.
AB  - There are thousands of unique neurons and many types of glia in the insect
      central nervous system. How is this cell diversity generated? Neurogenesis begins
      with the delamination and enlargement of individual cells of the ventral ectoderm
      to form a stereotyped array of neuroblasts. Every neuroblast divides
      asymmetrically to generate a chain of approximately 10 smaller progeny, each of
      which produces a pair of neurons. Ablation, transplantation and in vitro culture
      experiments illuminate the role of cell interactions and cell lineage during
      neurogenesis, and genetic approaches in Drosophila are beginning to provide
      insight into the molecular mechanisms controlling these events.

PMID- 1983316
TI  - Homoeotic genes.
AB  - Region specific differentiation in Drosophila, (and possibly in many other higher
      organisms), is controlled by the activity of families of transcription factors
      encoded by the homoeotic genes. In Drosophila these genes are clustered in two
      complexes: the Antennapedia complex is responsible for directing the
      differentiation of the head and thoracic body segments whereas the bithorax
      complex controls the differentiation of the thorax and abdomen. The precise way
      in which these genes work is still a mystery but both the levels and combinations
      of gene activities play an important role in directing the development of
      individual segments.

PMID- 1983318
TI  - [Functional structure of the Auerbach's plexus and intestinal peristalsis].

PMID- 1983317
TI  - Flexure strength of nickel base solder joint through the different cooling
      methods.

PMID- 1983319
TI  - Effects of amiloride on the contraction of mesenteric artery induced by
      transmural nerve stimulation.

PMID- 1983320
TI  - [The immune and nonimmune genesis of goiter].

PMID- 1983321
TI  - Omeprazole or high-dose ranitidine in the treatment of patients with reflux
      oesophagitis not responding to 'standard doses' of H2-receptor antagonists.
AB  - Ninety-eight patients (26 females), who presented with erosive and/or ulcerative
      oesophagitis, despite at least a 3-month period of treatment with standard doses
      of cimetidine (greater than or equal to 1200 mg daily) or ranitidine (greater
      than or equal to 300 mg daily), were included in a double-blind, randomized trial
      to compare omeprazole (40 mg o.m.) with a high dose of ranitidine (300 mg b.d.).
      The treatment was given for 4-12 weeks; endoscopy assessment and laboratory
      screening were performed on entry to the trial and thereafter every fourth week.
      Endoscopic healing was defined as complete epithelialization of all macroscopic
      erosions or ulcers in the squamous epithelium. An 'intention-to-treat' analysis
      of the clinical data revealed omeprazole to be superior to ranitidine: 63% of
      those patients who were given omeprazole were healed endoscopically after a 4
      week period of treatment, compared with only 17% of those given ranitidine. This
      difference in healing rate persisted during the 12-week study period (90% vs 47%
      after 12 weeks; P less than 0.0001). Reflux symptoms were more rapidly and
      completely relieved with omeprazole: heartburn resolved completely in 86% of
      patients treated with omeprazole for 4 weeks compared with 32% in the ranitidine
      group (P less than 0.0001). The mean basal gastrin concentrations increased only
      in those given omeprazole from 18.9 pmol/L at pre-entry to a mean value of 31.7
      pmol/L on the last day of omeprazole administration. In ranitidine-treated
      patients no significant increase in basal gastrin concentration was observed.
      Both drugs were well tolerated with few adverse events, which were mainly mild
      and transient. These results demonstrate the superiority of omeprazole over a
      high dose of ranitidine in the treatment of resistant reflux oesophagitis.

PMID- 1983322
TI  - A comparison of two doses of nizatidine versus placebo in the treatment of reflux
      oesophagitis.
AB  - Three-hundred and twenty-five patients with endoscopically verified oesophagitis
      entered a double-blind, randomized multicentre study that compared 300 mg
      nizatidine b.d., 300 mg nocte and placebo. The 6- and 12-week treatment responses
      were studied. Healing was defined as complete epithelialization of all
      oesophageal lesions. The healing rates were 40% in the 300 mg nizatidine b.d.
      group, 30% in the 300 mg nocte group and 26% in the placebo group at 6 weeks. The
      corresponding figures after 12 weeks of treatment were 50%, 44% and 34%,
      respectively. The healing rates were significantly different (P less than 0.05)
      between the high-dose nizatidine group and placebo only, both at 6 and 12 weeks.
      Despite a trend at both 6 and 12 weeks in favour of 300 mg nizatidine nocte
      compared to placebo, this was not significantly different. The most important
      factor for the outcome, apart from the treatment group, was the pre-entry
      severity of oesophagitis. The differences observed between treatment groups in
      healing rates, symptomatic relief, and antacid consumption appear to result
      mainly from the patients with moderate and severe oesophagitis upon entry.
      Nizatidine (300 mg) b.d. appeared to be safe and effective in the treatment of
      reflux oesophagitis.

PMID- 1983323
TI  - Immune complex induced experimental colitis: beneficial effect of sulphasalazine
      in rabbits.
AB  - Experimental colitis was induced in rabbits by exposing the colon mucosa to 1%
      formalin followed by i.v. injections of soluble immune complexes made with
      antigen in excess. The animals were preimmunized with Escherichia coli O14:K7:H-
      inducing antibodies cross-reactive to intestinal epithelium. Animals with this
      colitis were divided in two groups. One group was treated with sulphasalazine and
      the other was given vehicle only. Sulphasalazine was administered daily at 125.5
      mumol (50 mg) per kg body weight. The administration was started at the same day
      as the colitis was initiated. At Day 6, 13 and 30 following induction of colitis,
      biopsies were sampled and histologically evaluated. Inflammation was assessed by
      scores for inflammatory cells, crypt distortion, decreased crypt number and
      presence of crypt abscesses, thus corresponding to the picture seen in humans. A
      statistically significant lower score of inflammation was seen on Day 6 and 13 (P
      less than 0.01) and on Day 30 (P less than 0.05) following induction of colitis
      in animals treated with sulphasalazine.

PMID- 1983324
TI  - Maintenance therapy of duodenal ulcer with H2-receptor antagonists--a meta
      analysis.
AB  - A theoretical basis for similar recurrence rates among H2-receptor antagonists
      exists based on recent concepts of ulcer recurrence, ulcer healing and
      suppression of nocturnal gastric acidity. In order to compare H2-receptor
      antagonists in the maintenance therapy of duodenal ulcer, a meta-analysis was
      carried out using 29 studies in the literature that met strict criteria. When the
      results of the placebo-controlled studies were expressed as odds ratios, a
      technique used to minimize differences in protocol design and patient populations
      among studies, cimetidine, ranitidine, famotidine and nizatidine were all found
      to be superior to placebo to approximately the same extent. Odds ratios (and 95%
      confidence limits) for the recurrences in the pooled studies were cimetidine 0.22
      (0.18-0.28), ranitidine 0.23 (0.18-0.30), famotidine 0.28-0.31 and nizatidine
      0.36. These reflected similar 1-year recurrence rates of 24.9% (n = 530) for 400
      mg cimetidine nocte, 22.4 (n = 508) for 150 mg ranitidine nocte, 28.0% (n = 371)
      for 20 mg or 40 mg famotidine nocte, and 21.8% (n = 261) for 150 mg nizatidine
      nocte. In studies to compare cimetidine and ranitidine directly, the odds ratio
      (and 95% confidence limits) was 0.64 (0.48-0.86). However, for two studies done
      by a single protocol, the odds ratio of 0.51 (0.35-0.75) tended to differ from
      the odds ratio of 0.85 (0.54-1.33) for six other studies (P = 0.09). These
      reflected recurrence rates for cimetidine and ranitidine of 28.3% and 16.8% (two
      studies) and 23.3% and 20.6% (six studies) respectively.

PMID- 1983325
TI  - Omeprazole in the treatment of peptic ulcers resistant to H2-receptor
      antagonists.
AB  - Thirty patients with peptic ulcers resistant to at least 8 weeks of continuous
      therapy with full-dose H2-receptor antagonists alone or followed by other anti
      ulcer drugs, were treated with the gastric proton pump inhibitor omeprazole (40
      mg), administered orally once daily for up to 8 weeks. The study design was non
      comparative and open; healing was verified by endoscopy. After only 2 weeks of
      treatment, 21 out of 23 (91%) duodenal ulcer patients were healed, as well as 2
      out of 2 patients with both duodenal and gastric ulcer and 1 out of 3 patients
      with prepyloric ulcer. After 4 weeks, all duodenal ulcers, 1 out of 2 gastric
      ulcers and 2 out of 3 pre-pyloric ulcers were healed. A further month of therapy
      healed the gastric ulcer to give an overall healing rate of 97% and leaving only
      one patient (pre-pyloric ulcer) unhealed at the end of the study. Of 19 patients
      suffering ulcer symptoms at entry, only two patients reported any symptoms at 2
      weeks and one of these (who remained unhealed) continued to have symptoms
      throughout the study. One patient reported mild asthenia; otherwise, no clinical
      or biochemical side-effects were recorded. It is concluded that omeprazole is
      highly effective in healing refractory peptic ulcers.

PMID- 1983326
TI  - [Necrotizing vasculitis of the panarteritis nodosa type in a long-course primary
      Sjogren's syndrome].
AB  - Vasculitis is a complication happening in a third of patients with primary
      Sjogren's Syndrome. It can be of 2 types: neutrophilic or mononuclear and
      sometimes mixed. Very occasionally, a necrotizing vasculitis polyarteritis nodosa
      type during the evolution of Sjogren's Syndrome has appeared. A case of a female
      patient with a Sjogren's Syndrome of large evolution, who suddenly showed a poly
      systemic affliction (nervous system, kidneys, muscles and digestive system)
      secondary to a necrotizing vasculitis type polyarteritis nodosa with a good
      response to immunosuppressors, is presented.

PMID- 1983327
TI  - [Electrocardiographic changes caused by ionic disorders and drugs].

PMID- 1983328
TI  - Intrathyroidal lymphocytes from non toxic multinodular goiter: no evidence for
      production of thyroid stimulating antibodies.
AB  - Although an autoimmune pathogenesis for non toxic goiter has been suggested,
      reports concerning circulating antibodies to TSH receptor structures have been
      conflicting. Intra thyroid lymphocytes, capable of secreting IgG, have been shown
      to be involved in the pathogenesis of Graves' and Hashimoto's diseases;
      therefore, the ability of conditioned media obtained from intra thyroid
      lymphocyte culture, and of IgG purified from these media, to stimulate cAMP
      accumulation and [3H]-Thymidine (TdR) uptake in FRTL-5 cells was investigated.
      The activity of IgG produced "in vitro" was compared with that of circulating
      IgG. Thyroid tissue samples were obtained at surgery from 21 patients with non
      toxic multinodular goiter (MNG), 5 patients with active Graves' disease (GD), and
      from 10 normal subjects, undergoing neck surgery for non-thyroidal pathology. IgG
      purified from media of GD lymphocyte cultures stimulated both cAMP accumulation
      and [3H]-TdR in 5 out of 5 cases: all of the IgG purified from control or MNG
      lymphocyte culture media was not active in either assay. Circulating IgG did not
      affect cAMP accumulation or [3H]-TdR in any of the non toxic MNG cases: controls
      showed no changed at all. However, both activities represented were increased by
      GD IgG. Conditioned media from intra thyroid lymphocyte cultures significantly
      inhibited basal cAMP accumulation in 7 out of the 21 non toxic MNG samples and
      totally abolished the response in all GD patients. [3H]-TdR was not affected by
      IgG of any of the controls, but it had an inhibitory effect on 8 out of 21 non
      toxic MNG patients, and significantly stimulated [3H]-TdR in all GD patients. In
      conclusion, present data demonstrate that intra thyroid lymphocytes from non
      toxic MNG do not produce antibodies capable of mimicking TSH actions through the
      adenylate cyclase cascade. Conversely, soluble factors interacting in TSH
      mediated functions of FRTL-5 cells are present in conditioned media of intra
      thyroid lymphocytes of GD and MNG thyroid lymphocytes of GD and MNG thyroid
      cultures.

PMID- 1983329
TI  - Thyroid autoantibodies in black and in white children and adolescents with type 1
      diabetes mellitus and their first degree relatives.
AB  - Genetic susceptibility is an important issue in understanding the mechanism of
      the autoimmune endocrinopathies and in assessing the risk of these conditions in
      pediatric patients. To this end, we evaluated autoantibodies to thyroid antigens,
      thyroglobulin (TgA) and microsomal antigen (TMA), in white and in American black
      juvenile patients with Type I diabetes mellitus (DM) to determine the predictive
      value of thyroid autoantibodies for the development of autoimmune thyroid
      disease. Sera from 159 patients (77 black and 82 white) with Type I DM were
      evaluated. A greater number of whites (41/82 or 50%) than blacks (12/72 or 16%)
      had thyroid autoantibodies (p less than 0.01). Fourteen patients (4 black and 10
      white) exhibited hypothyroidism, and all had both TgA and TMA. Three patients
      (all black) had Graves' disease, one of whom had both TgA and TMA. Families of
      each racial group that had a diabetic child (proband) with thyroid autoantibodies
      (seropositive) or without thyroid autoantibodies (seronegative) were assessed for
      TgA and TMA as well as autoimmune thyroid disease. The prevalence of thyroid
      autoantibodies among siblings of seropositive probands was significantly greater
      than among the siblings of seronegative probands (p less than 0.01). The white
      sibling population showed a closer association of thyroid autoantibody prevalence
      with increasing age (p less than 0.05) than the blacks. Significantly more
      parents of probands than control parents exhibited thyroid autoantibodies (p less
      than 0.01). The general pattern of inheritance of either racial group showed that
      if one or both parents had thyroid autoantibodies, their progeny developed a
      significantly higher prevalence of thyroid autoantibodies than those of the
      seronegative parents. While there was no increase in overt thyroid disease among
      siblings of seropositive probands, a risk of developing autoimmune thyroid
      disease is probably imparted to these siblings by virtue of the thyroid
      autoantibodies.

PMID- 1983331
TI  - Association of DR4 related RFLP bands and RA in Greeks.
AB  - Using the Taq1 restriction enzyme and DR beta, DQ alpha probes, the DNAs of Greek
      RA patients and controls were characterised for RFLP's associated with DR4. Three
      DR beta bands, 14.8kb, 6.1kb and 5.4kb were observed at significantly higher
      frequency in the patients compared with controls. By using a DQ alpha probe, the
      2.6kb band (associated with DR1, DRw10, DRBR and DRw14 (Dw9)) was at a
      significantly raised frequency in the patients. The DQ alpha 5.3kb band
      associated with DR4, DR7 and DR9 was also raised in the RA patients although this
      increase did not reach statistical significance. In view of the previously
      documented lack of association between DR4 (and other DR antigens) and RA in
      Greeks, the results suggest that some degree of HLA class II association exists
      with RA in this population at the DNA level which may not be overtly reflected
      serologically.

PMID- 1983330
TI  - Changes in thyrotropin receptor antibody after subtotal thyroidectomy in Graves'
      disease: comparison with the degree of lymphocytic infiltration in the thyroid.
AB  - To evaluate changes in TSH receptor antibody after surgery in Graves' disease and
      its relationship with the degree of lymphocytic infiltration, serial serum levels
      of TSH receptor antibody were measured before and after the subtotal
      thyroidectomy in 50 patients with Graves' disease. In 22 (44%) out of 50
      patients, thyrotropin binding inhibitor immunoglobulin (TBII) levels gradually
      decreased and disappeared completely within 12 months after surgery (TBII
      disappearing group). Twenty-eight (56%) patients showed persistent TBII activity
      and their levels were not changed until 12 months after surgery (TBII persistent
      group). The changes of thyroid stimulating antibody (TSab) levels were very
      similar to those of TBII in both groups. The thyroidal lymphocytic infiltration
      was more prominent in the TBII disappearing group. The degree of the decrease of
      TBII levels after surgery correlated with the grade of thyroidal lymphocytic
      infiltration. There was no significant difference of TSH receptor antibody (both
      TBII and TSab) levels between the thyroid and peripheral venous blood. These data
      suggest that the persistence or disappearance of TSH receptor antibody after
      surgery may reflect the difference between patients in whom the thyroid is the
      major site of TSH receptor antibody and those in whom additional sites of TSH
      receptor antibody synthesis exist.

PMID- 1983333
TI  - Interleukin 1 responsiveness and receptor expression by murine TH1 and TH2
      clones.
AB  - Murine Th1 and Th2 T cell lines differ in their responses to interleukin 1 (IL
      1). Therefore, we examined two T-cell lines, D10.G4.1 (Th2) and MTg12B (Th1) in
      an attempt to correlate IL 1 receptor (IL 1R) expression with their IL 1
      responsiveness. D10.G4.1 cells, which respond to IL 1, expressed two forms of the
      IL 1R, with molecular masses of approximately 80 kDa and approximately 60 kDa. In
      contrast, MTg12B cells failed to respond to IL 1 and only expressed the
      approximately 60 kDa receptor form. This suggests that the approximately 80 kDa
      receptor is essential for signaling. Expression of both IL 1R forms on D10.G4.1
      cells could be inhibited by the anti-IL 4 antibody, 11B11. Antigen presentation
      reversibly upregulated both forms of the IL 1R, whereas stimulation with
      concanavalin A (ConA) and anti-CD3 only upregulated the approximately 60 kDa
      moiety. Upregulation of the approximately 80-kDa IL 1R by repeated antigenic
      stimulation resulted in a marked increase in sensitivity of D10.G4.1 cells to IL
      1.

PMID- 1983332
TI  - Changes in myocardial mitochondrial respiration after ligation of the coronary
      artery in pigs.
AB  - After ligation of the left coronary artery, porcine cardiac mitochondria were
      isolated by homogenizing the tissue and treating the myofibrillar pellet with
      nagarse. When compared with unligated controls, the ischemic myocardium showed
      decreases in phosphocreatine (to 41%), ATP (to 56%) and in the mitochondrial
      respiratory control index (to 69% and 78% as measured with glutamate and
      succinate respectively). No changes were found in the corresponding P/O ratios.
      Similar results were obtained upon separation of the mitochondria into two main
      fractions by a density gradient technique, though only one of these fractions
      showed a fall in succinate-supported respiration. The results suggest that
      ischemia decreases the NADH-dehydrogenase activity of cardiac mitochondria.

PMID- 1983335
TI  - T cell regulation of autoimmune interstitial nephritis.
AB  - Research in organ-specific autoimmunity has been greatly facilitated over the
      past decade by advances in cellular and molecular immunology. Such studies have
      greatly expanded our understanding of autoimmune effector mechanisms and the
      nature of the target antigens recognized by these mediators. Another facet of
      organ-specific autoimmunity concerns the definition of those factors that
      determine host susceptibility to disease. This review outlines studies performed
      in two models of autoimmune interstitial nephritis that focus on issues of
      susceptibility and tolerance to parenchymal self antigens. In both models,
      antigen-specific regulatory T cells modulate the effector limb of the
      nephritogenic immune response and the pattern of interstitial injury. This
      modulation can be either stimulatory or inhibitory. The dominant regulatory
      effect is linked to genes in the major histocompatibility locus and is tightly
      correlated with disease expression. Regulatory T cells which inhibit the
      nephritogenic immune response can also be cultured in vitro and are highly
      efficacious as a therapeutic modality. These studies provide both the background
      and requisite reagents for delineating the mechanism(s) underlying antigen
      specific T cell regulation.

PMID- 1983334
TI  - Evolutionary aspects, structure, and expression of the rat interleukin 4 gene.
AB  - The rat interleukin 4 (IL 4) gene has been isolated from a genomic lambda phage
      library by cross-hybridization to the mouse IL 4 cDNA. Like the mouse and human
      counterparts, it exists as a single copy gene in the genome and consists of four
      exons. The overall structure of the IL 4 locus seems highly conserved. This is
      indicated by the low degree of restriction fragment length polymorphism in a
      number of laboratory and wild mice and by the conservation of the intron size
      between human, rat, and mouse IL 4 genes. Furthermore, evolutionary conserved
      elements are the promoter region, the position of cysteine residues and sequence
      motifs in the 3' untranslated regions that are believed to be involved in
      destabilization of the mRNA. In contrast, the predicted amino acid sequence of
      the rat IL 4 gene shows low homology (57%) with the mouse homologue. The
      divergence between mouse and rat IL 4 genes is even more pronounced in the
      carboxy-terminal region (47% homology in the last 68 amino acids). The ratio
      between replacement and silent mutations in the IL 4 genes of different species
      suggests a complex pattern of selective forces acting on the IL 4 gene, which
      includes both selection against and for amino acid substitutions in individual
      positions. The functional identity with IL 4 has been confirmed by expression of
      the gene and the demonstration of the ability to induce MHC class II antigen
      expression on spleen cells.

PMID- 1983336
TI  - Endocytosis and antigen processing.
AB  - It has become increasingly clear that endocytosis plays a critical role in the
      processing of exogenous antigens for presentation to T lymphocytes. However, many
      critical questions remain concerning the pathways taken by antigens and MHC
      molecules following internalization by antigen presenting cells. This review
      summarizes current information concerning the general features and functions of
      the endocytic pathway in mammalian cells. We also identify the likely roles of
      the various endocytic organelles in each of the events associated with antigen
      processing.

PMID- 1983337
TI  - Contribution of endosomal acidification to antigen processing.
AB  - The role of endosomes in antigen processing was investigated with mutant cells,
      expressing a temperature-sensitive defect in endosomal acidification, as a source
      of antigen-presenting cells for CD4+ T cell responses. When the mutants were
      incubated at the nonpermissive temperature, their ability to process a variety of
      native antigens was greatly impaired. These cells could present peptide fragments
      normally, and the higher temperature did not affect antigen processing by the
      wild-type parental cells. The mutant cells do not have a defect in the
      internalization and overall degradation of native antigen. Upon return to the
      permissive temperature, the mutant cells rapidly recover their ability to process
      antigen. Therefore, acidified early endosomes have an important function in
      antigen processing, and other acidified organelles may also be involved.

PMID- 1983338
TI  - The antigen processing pathway in B lymphocytes.
AB  - Monovalent antigen bound to membrane immunoglobulin on human B lymphoblastoid
      cells is endocytosed through coated pits and passes sequentially from a site
      which actively recycles membrane to the cell surface and then to a
      proteolytically active processing site. A high affinity of immunoglobulin for
      antigen precludes antigen dissociation following endocytosis and results in the
      processing of an antigen/Ig complex yielding an epitope-specific pattern of
      processing. Processing of the immunoglobulin also occurs and is enhanced by
      occupancy with monovalent antigen.

PMID- 1983339
TI  - Catheptic processing of protein antigens: enzymic and molecular aspects.
AB  - Processing of most exogenous protein antigens involves restricted intracellular
      proteolysis to yield fragments that may be bound specifically by MHC class II
      glycoproteins. This association is required for functional presentation to
      antigen-specific T lymphocytes. The proteolytic degradation takes place in
      antigen-presenting cells, in an acidic, endosomal compartment where antigens
      arrive after capture and internalization. It is catalyzed by a small number of
      enzymes, mainly aspartic and thiol proteases, with the cathepsins D and B--in
      that order--as dominant representatives. Resulting immunogenic protein fragments
      possess a binding site for mature MHC molecules and a recognition site for T cell
      receptors; topologically, these sites are interspersed, generally extending over
      7-8 consecutive amino acid residues. Binding of peptides by MHC proteins of a
      particular genotype appears to depend mainly on specific interactions involving a
      common sequential motif in their primary structure in terms of non-polar and
      polar/charged amino acid residues and not on a general propensity to adopt a
      certain regular secondary structure, such as an alpha-helix.

PMID- 1983340
TI  - In-vivo brain dialysis of neurotransmitters.
AB  - Centrally acting drugs interfere with the function of central neurotransmitter
      systems. This often requires intact neuronal connections and is therefore best
      studied in vivo. Here, Gaetano Di Chiara describes the technique of brain
      dialysis, which permits direct in-vivo sampling of neurotransmitters and their
      metabolites in the brain extracellular fluid. This technique is now providing
      insight correlating the interaction of drugs with neurotransmission in specific
      brain areas with their effects on behaviour.

PMID- 1983341
TI  - 1,25-Dihydroxyvitamin D3 decreases the interferon-gamma (IFN-gamma) induced HLA
      DR expression but not intercellular adhesion molecule 1 (ICAM-1) on human
      keratinocytes.
AB  - In human epidermal keratinocytes (HKC), it is known that interferon gamma (IFN
      gamma) induces Major Histocompatibility Complex (MHC) class II antigens and
      intercellular adhesion molecule 1 (ICAM-1) expression. 1,25 (OH)2D3, the most
      active metabolite of vitamin D3, has been shown to be produced by keratinocytes
      (KC). KC possess receptors for 1,25 (OH)2D3 and could be a target of 1,25
      (OH)2D3. Although immunological participation of 1,25 (OH)2D3 has been reported,
      little is known about its effect on MHC class II Ag expression or ICAM-1
      expression. In this article, we investigate the effect of 1,25 (OH)2D3 on IFN
      gamma induced MHC class II Ag or ICAM-1 expression of HKC and reveal that 1,25
      (OH)2D3 decreases the IFN-gamma induced HLA-DR, but not ICAM-1 expression on HKC.

PMID- 1983342
TI  - Prospective evaluation of omeprazole treatment in reflux oesophagitis refractory
      to H2-receptor antagonists.
AB  - The efficacy of omeprazole therapy (40 mg daily) in H2-blocker refractory severe
      reflux oesophagitis (Grade II-IV; Savary and Miller classification) was
      investigated in 61 patients. Mean duration of reflux disease and preceding H2
      antagonist treatment were 4.3 years and 15 months, respectively. Healing rates at
      4, 8 and 12 weeks were 48%, 80% and 92%, respectively. There was a correlation
      between severity of oesophagitis and duration of omeprazole therapy necessary for
      healing. Three patients (5%) required higher dosages than 40 mg for healing.
      Symptomatic responses paralleled healing. It is concluded that omeprazole is a
      highly effective drug for severe reflux oesophagitis not responding to H2-blocker
      treatment and that 40 mg daily is the optimal dose.

PMID- 1983343
TI  - H2-receptor antagonists: intragastric acidity after repeated doses. Introduction.

PMID- 1983344
TI  - Loss of acid suppression during dosing with H2-receptor antagonists.
AB  - The suppression of intragastric acidity with H2-receptor antagonists may diminish
      with repeated administration. To assess the degree and dose-dependence of this
      tolerance after short-term dosing, two doses of the H2-receptor antagonists,
      ranitidine (300 mg nocte or q.d.s.) and sufotidine (300 mg or 600 mg b.d.), were
      given to healthy volunteers for 1 and 2 weeks, respectively. After 1 and 7 days
      of dosing with ranitidine 300 mg q.d.s. the median 24-h and night-time pH,
      measured by continuous 24-h pH-metry, dropped from 3.7 to 2.2 and 5.8 to 3.2,
      respectively (P less than 0.0001 for both). The decline in median pH with
      ranitidine 300 mg nocte was only significant during the night (from 4.1 to 2.9)
      (P less than 0.04). There was little change in plasma gastrin concentrations
      between days 1 and 7 with either dosage. With sufotidine 300 mg b.d. and 600 mg
      b.d. for 1 and 14 days, the median 24-h pH fell from 3.7 to 2.1 and from 4.6 to
      2.6, respectively (P less than 0.0001). The equivalent medians for the night
      decreased from 6.3 to 2.3 and from 6.6 to 3.1 (P less than 0.0001). Gastrin
      concentrations did not change after 14 days of dosing with sufotidine 300 mg
      b.d., but increased significantly during dosing with sufotidine 600 mg b.d. (P
      less than 0.001). Significant tolerance developed in 7-14 days and it seemed to
      show some dose relationship. The mechanisms behind tolerance and the role of
      gastrin are discussed, but remain unclear.

PMID- 1983345
TI  - Tolerance during 29 days of conventional dosing with cimetidine, nizatidine,
      famotidine or ranitidine.
AB  - Twenty-four-hour intragastric acidity and 24-h plasma gastrin concentration were
      measured on four occasions in six groups of eight healthy male subjects. Each
      group was studied before dosing, and on days 1, 15 and 29 of dosing with a
      standard regimen of an H2-receptor antagonist (cimetidine 800 mg nocte,
      nizatidine 300 mg nocte, famotidine 40 mg nocte, ranitidine 150 mg nocte,
      ranitidine 150 mg b.d., or ranitidine 300 mg nocte). On the first day of dosing,
      each regimen using an H2-antagonist caused a significant decrease of intragastric
      acidity and a significant rise of plasma gastrin concentration. Continued dosing
      with each H2-antagonist resulted in a significant attenuation of the effect on
      intragastric acidity, which was most noticeable overnight, but no significant
      change of plasma gastrin concentration. When grouped together, median integrated
      nocturnal acidity for the 48 subjects was 485, 35, 67 and 117 mmol.h/L for days
      0, 1, 15 and 29, respectively, associated with a median nocturnal integrated
      plasma gastrin concentration of 46, 72, 79 and 73 pmol.h/L. The study
      demonstrates that a degree of tolerance develops during continued dosing with all
      available H2-receptor antagonists, and that this phenomenon occurs during
      sustained elevation of plasma gastrin concentration.

PMID- 1983346
TI  - Tolerance during 8 days of high-dose H2-blockade: placebo-controlled studies of
      24-hour acidity and gastrin.
AB  - Simultaneous 24-h intragastric and plasma gastrin concentrations were measured in
      36 healthy subjects, when receiving placebo (day 0) and on days 1 and 8 of dosing
      with either placebo (n = 8), or high-dose H2-blockade with either ranitidine 300
      mg q.d.s. (n = 8), ranitidine 1200 mg o.m. (n = 8), or sufotidine 600 mg b.d. (n
      = 12). Triplicate placebo studies demonstrated good reproducibility for this
      technique, with no significant differences of acidity or plasma gastrin
      concentration between the studies. There was a decrease in the anti-secretory
      activity of all three high-dose H2-antagonist regimens on day 8, when compared
      with that observed on day 1. This occurred in the presence of sustained or
      increasing hypergastrinaemia. It is concluded that a degree of tolerance develops
      during continued H2-blockade, and that this could be due to increasing gastrin
      drive to the parietal cells.

PMID- 1983347
TI  - The effects of 15 days of dosing with placebo, sufotidine 600 mg nocte or
      sufotidine 600 mg twice daily upon 24-hour intragastric acidity and 24-hour
      plasma gastrin.
AB  - The acid inhibitory effect of sufotidine, a potent, long-lasting, competitive H2
      receptor antagonist, was studied in 12 healthy males in a double-blind,
      randomized, three-way cross-over study of the effect of placebo, sufotidine 600
      mg nocte and sufotidine 600 mg b.d. given over 15 days. On day 1 and 15 of dosing
      with each regimen, each subject's 24-h ambulatory intragastric acidity was
      measured by radiotelemetry and 24-h plasma gastrin profiles were derived from
      hourly venous blood samples. Acid suppression was calculated as the decrease in
      the area under the curve of hydrogen ion activity vs time from that observed on
      placebo, and 24-h plasma gastrin calculated as the area under the curve of plasma
      gastrin concentration vs time. Twenty-four hour intragastric acidity during the
      fifteenth day of dosing with sufotidine 600 mg nocte and sufotidine 600 mg b.d.
      did not differ significantly, but on the first and fifteenth day of dosing
      nocturnal acidity was decreased to a greater extent by sufotidine 600 mg nocte
      than sufotidine 600 mg b.d. (P less than 0.005). After 15 days, the acid
      suppression afforded by sufotidine 600 mg b.d. was significantly attenuated (P
      less than 0.0005); this was associated with a rise in 24-h plasma gastrin (P less
      than 0.001). Thus, tolerance to the acid inhibitory effect of H2-receptor
      antagonists exists and is of rapid onset. We suggest that tolerance is mediated
      by the temporally associated rise in 24-h plasma gastrin, but we cannot exclude
      the possibility that other mechanisms, such as up-regulation of H2-receptors,
      also play a part.

PMID- 1983348
TI  - Chronic administration of H2-antagonists does not alter gastric secretory
      responses to histamine, or the antisecretory activity of sufotidine.
AB  - Gastric secretory responses to histamine were investigated in anaesthetized dogs
      following treatment with oral ranitidine at 5 mg/kg twice daily for 358 weeks,
      and in isolated gastric mucosae from mice receiving sufotidine 240-280 mg.kg/day
      for 15 months. In neither study were there any significant differences between
      the acid secretory dose-response curves to histamine in control and test animals.
      The antisecretory activity of oral sufotidine (1 mg/kg) against histamine-induced
      acid secretion in the Heidenhain pouch dog was unaltered by twice daily dosing
      with sufotidine for 14 days. These studies on the effects of H2-antagonists on
      histamine-stimulated acid secretion found no evidence for development of direct
      tolerance at the parietal H2-receptor level.

PMID- 1983349
TI  - Intravenous pentagastrin can induce the illusion of 'tolerance' to a single dose
      of an H2-blocker in man.
AB  - In a double-blind study of Latin square design, twelve healthy male subjects were
      dosed with combinations of ranitidine 300 mg or placebo (at 08.50 hours) and
      intravenous pentagastrin (0.6 microgram.kg/h) or 0.9% saline (07.00-18.00 hours).
      Breakfast and lunch were served at 08.15 and 13.15 hours, respectively; hourly
      intragastric acidity and plasma gastrin concentration were measured from 08.00
      18.00 hours. During oral dosing with placebo, intravenous pentagastrin raised
      median 10-h integrated intragastric acidity (315 to 615 pmol.h/L; P less than
      0.001) and lowered gastrin (86 to 55 mmol.h/L; P less than 0.001). During oral
      dosing with ranitidine 300 mg, compared with intravenous saline, the pentagastrin
      infusion returned acidity towards normal (67 to 293 pmol.h/L; P less than 0.001)
      and lowered gastrin (209 to 135 pmol.h/L; P less than 0.001). This study
      demonstrates that a continuous pentagastrin infusion can overcome H2-blockade and
      return intragastric acidity towards normal. Hypergastrinaemia observed during
      continued dosing with an H2-blocker may be the mechanism for the development of
      tolerance.

PMID- 1983350
TI  - Clinical relevance of tolerance to peptic ulcer healing and relapse.

PMID- 1983351
TI  - In vivo cloning of proline genes and its expression in Escherichia coli.
AB  - The wild type proA+, B+ genes of E. coli were cloned in vivo using a plasmid
      containing a mini-Mu replicon, pEG5005. The cloning frequency was about 1.46 x
      10(-3)/Kanr transductant. Genetic and biochemical analysis of these clones
      indicated that the proA+, B+ genes are on the plasmid pEG5005. The secretion of
      proline were assayed for 500 Pro+ clones. However, no proline accumulation was
      detected. A Pro+ clone pPR3 was mutagenized in vivo by NTG and the mutants
      resistant to D-proline were obtained. One of the Dpr mutants pPR7 was found to
      produce 0.35 mg/ml proline in a proA B deletion strain. When pPR7 was transferred
      into a proline producing strain, the yield of proline increased up to 2.5 mg/ml,
      which is 7 and 2.5 times higher than that of the donor and recipient
      respectively. The physical maps of pEG5005 and pPR3 were roughly established.

PMID- 1983352
TI  - Anxiolytic-like action of DuP753, a non-peptide angiotensin II receptor
      antagonist.
AB  - The potential of DuP753, an angiotensin II receptor antagonist, to inhibit the
      suppressed behaviour of mice in a light/dark aversion test was investigated. The
      aversive response to the light compartment of the apparatus was reduced (increase
      in latency to move from the light to the dark compartment and decreases in rears,
      line crossings and percentage of time spent in the dark compartment) following
      treatment with DuP753 (0.1-1000 micrograms kg-1 p.o., 45 min before the test).
      These results further implicate the modulation of mental function by angiotensin
      II.

PMID- 1983353
TI  - Ethanol inhibits NMDA-stimulated neurite growth by sensory neurons in vitro.
AB  - N-methyl-D-aspartate (NMDA) produced dose dependent neurite growth from 8 day
      chick embryo sensory neurons in-vitro on a laminin substrate. NMDA-stimulated
      neurite growth was blocked by the competitive antagonist D-2-amino-5
      phosphonovaleric acid (APV), by an antagonist of the glycine modulatory site
      kynurenate, and by the NMDA ion channel antagonist Mg2+. Ethanol blocked the NMDA
      mediated neurotrophic effect in a manner that was additive with the effects of
      Mg2+, but non-additive with the inhibitory influences of APV and kynurenate. Thus
      the influences of ethanol were mediated at the NMDA receptor/modulatory site.
      These observations have implications for the understanding of adverse influences
      of ethanol on neuronal development and connectivity and on activity-dependent
      enduring changes in synaptic changes in synaptic function.

PMID- 1983354
TI  - Role of dopamine in anterior pituitary tubulin pools in the lactating rat.
AB  - In lactating rats, suckling stimulated the in-vitro tubulin assembly of cold
      labile pituitary tubulin fraction by about 70%. Domperidone and alpha methyl-p
      tyrosine stimulated the pituitary tubulin assembly by 90% and 325%, respectively.
      In another experiment, pituitaries from a group of lactating rats (no reference
      to suckling) were processed to obtain cold-labile and cold-stable tubulin
      fractions; total tubulin fraction was obtained from another group. Tubulin
      assembly in the total and cold-stable tubulin fractions was 17-20 fold higher
      compared to cold-labile fraction. Since the cold-stable and total tubulin
      fractions were extracted with a Ca(2+)-containing buffer, these results suggest
      that dopamine-induced changes in cytosolic Ca2+ levels modulate pituitary
      microtubules.

PMID- 1983355
TI  - Ascorbic acid protects neurons from injury induced by glutamate and NMDA.
AB  - We have previously shown that redox phenomena regulate the function of the NMDA
      receptor in the brain and that ascorbic acid (AA) behaves as a receptor
      antagonist. Here we examined the potential neuroprotective effects of AA against
      toxicity induced by NMDA and glutamate in rat cerebral cortical neurones in
      cultures. AA completely protected against injury induced by 100 microM NMDA and
      markedly reduced cell death induced by 500 microM NMDA or 50 microM glutamate.
      Dehydroascorbic acid (DHAA) did not provide significant neuroprotection. Hence,
      we propose that AA may serve in the CNS as a neuroprotectant.

PMID- 1983356
TI  - Oxytocin attenuates the cocaine-induced exploratory hyperactivity in mice.
AB  - The effects of pimozide, a dopamine-receptor blocker and oxytocin, a
      neurohypophyseal neuropeptide were investigated in mice on the cocaine-induced
      exploratory hyperactivity. The action of oxytocin on changes of dopaminergic
      neurotransmission induced by cocaine was also measured. Cocaine-induced
      exploratory hyperactivity could be blocked by pimozide (1 mg kg-1, s.c.).
      Oxytocin (0.05-1.0 micrograms) inhibited the cocaine-induced hyperactivity in an
      U-shaped dose-response manner. In the nucleus accumbens, oxytocin antagonized the
      increased dopamine disappearance, elicited by cocaine, but not in the nucleus
      caudatus. The data suggest that oxytocin may influence the behavioural effect of
      cocaine by modulating dopaminergic neurotransmission in mesolimbic dopaminergic
      terminal region of the brain.

PMID- 1983357
TI  - Human neural graft function in rats treated with anti-interleukin II receptor
      antibody.
AB  - Prolonged immunosuppression with cyclosporin A allows survival of human
      xenografts in the rat Parkinsonian model but the drug has side effects. Ideally
      immunosuppression should be of short duration, to minimize the chance of
      infection, yet be capable of supporting long term survival of the transplanted
      tissue. We report that short term treatment with an anti-rat interleukin II
      receptor (IL2R) monoclonal antibody (MAb) resulted in apparently permanent
      survival of human fetal dopaminergic grafts in "Parkinsonian" rats. The
      recipients remained healthy and the excellent survival of the transplants
      suggests that the antibody injection strategy would almost certainly abrogate
      allograft rejection and raises the possibility that xenogenic dopaminergic
      neurones could be used as donor tissue in humans.

PMID- 1983358
TI  - Anxiolytic and sedative effects of 5-HT1A ligands, 8-OH-DPAT and MDL 73005EF, in
      mice.
AB  - The actions of the 5-HT1A receptor ligands, MDL 73005EF and 8-OH-DPAT, were
      assessed in mice. They were confronted with a free exploratory test especially
      adapted to reveal sedation, and with a two-box light/dark choice situation
      validated for the detection of anti-anxiety agents. Both drugs were found to have
      sedative properties at high doses and anxiolytic-like effects at lower doses. The
      results show that both drugs have a comparable profile of action to that of
      benzodiazepines in the two-box light/dark procedure. These findings are in line
      with earlier reports describing anxiolytic effects of 5-HT1A receptor ligands in
      different animal models of anxiety.

PMID- 1983359
TI  - Proceedings of the international symposium: Health Impact of Rapid
      Industrialization and Urbanization in Asia and the Pacific and its Public Health
      Activities.

PMID- 1983360
TI  - Proceedings of the International Workshop on Dietary Protein as a Regulator of
      Lipid Metabolism. August 28, 29, 1989, Fukuoka, Japan.

PMID- 1983361
TI  - Clinical application of electric resistance welding and soldering methods to
      removable partial dentures.
AB  - The joining procedure for uniting metal structures is very important in the
      construction of removable partial dentures. However, it has several restricted
      problems in joining wrought wire clasps to rests or major connectors. For
      example, the base metal wires made of chromium-cobalt alloy are subject to
      changes in their mechanical properties caused by heating, and damage to acrylic
      resin materials (denture base and artificial teeth) occurs in the repair of
      removable partial dentures by using the torch soldering method. In this paper, in
      order to resolve these problems, an electric resistance welding machine was
      applied to attach wrought wire components to a removable partial denture
      framework. This welding machine was used to attach metal structures temporarily
      to each other, and to solder the welded joint with hard solder. Consequently,
      some problems of the conventional torch soldering method were improved by using
      the electric resistance welding and soldering methods. It was suggested that the
      clinical application of the electric welding and soldering methods was very
      useful in the construction of removable partial dentures.

PMID- 1983363
TI  - Abstracts of the twelfth annual conference, the Hong Kong Society of
      Neuroscience. Hong Kong, August 30 and 31, 1990.

PMID- 1983362
TI  - [Influence of beta-adrenergic antagonists and agonists on dental caries
      development: an overview].
AB  - Patients with diseases of the respiratory tract are often treated with beta 1-
      and/or beta 2-adrenergic agonists. As undesired side-effects the beta-agonists
      cause alternations in the salivary glands and their protein synthetic apparatus.
      This results in alterations of the protein composition of saliva, resulting in a
      decrease of the protective function on the teeth, among others caused by the
      lowered production and secretion of the salivary mucins. Therefore, the dentist
      must be alert on the influence of the use of drugs on the dentition of patients
      with respiratory tract diseases.

PMID- 1983364
TI  - [Are cochlear outer hair cells the origin of otoacoustic emissions?].
AB  - Recent investigations have shown, that cochlear outer hair cells (OHCs) influence
      actively the micromechanics of the cochlea, beside their capability for auditory
      perception. A direct evidence for these energy requiring processes has been the
      registration of otoacoustic emissions in the external ear canal. Motile responses
      of isolated OHCs following various stimuli have been suggested to be the possible
      source of the postulated active mechanical processes. These motile events are
      possibly controlled by the efferent olivocochlear innervation. By means of two
      monoclonal antibodies, which were directed against external and internal
      acetylcholine (ACh) receptor epitopes, we were able to visualize ACh-receptors on
      OHCs. We suspect, that ACh is released into the synaptic cleft and binds to these
      newly observed receptors. Thereby they may influence the biomechanics of the
      cochlea.

PMID- 1983366
TI  - [The antihypertensive efficacy and tolerance of bopindolol (LT 31-200) in
      hypertensive patients].
AB  - A open study with increasing doses of bopindolol, a nonselective beta-blocker of
      long half-life has been carried out in patients with mild and moderate
      hypertension in order to assess the efficacy and security of the treatment in
      short and long term. Twenty patients (22 women and 8 men) were included with the
      ranging ages from 36 to 62 years old (x +/- SD 51.6 +/- 7.6) whose blood
      pressures were higher than 160 mm Hg for the systolic value and between 90 and
      125 mm Hg for the diastolic (x +/- SD 165 +/- 7.2 and 102.6 +/- 6.7
      respectively). Nineteen from the twenty patients (95%) responded satisfactorily
      after 20 weeks of oral bopindolol treatment once a day showing significative
      statistical differences on forth week of the treatment versus blood pressure
      rates of placebo's period. Similar results were obtained with regard to the
      cardiac frequency. HDL cholesterol rates increased significantly as well as the
      ratio HDL cholesterol/total cholesterol.

PMID- 1983367
TI  - [The correct use of beta stimulants by inhalation route].

PMID- 1983365
TI  - [A pharmacovigilance study with bentazepam in a sample of 1046 psychiatric
      outpatients].
AB  - A pharmacovigilance study was performed upon 1,046 ambulatory patients that have
      been treated in external psychiatric consultation with bentazepam. The sample
      size made possible to detect with 99% of security the incidence higher to 5%
      secondary effects, as mouth dryness, somnolence, asthenia,
      gastralgias/dyspepsias, constipation and sickness. It has as well been possible
      to detect the most usual ways of coprescription, and the most frequent was with
      antidepressants drugs that undertook approximately 1/3 of the sample and that it
      was responsible for some of the secondary effects observed. The bentazepam
      treatment cut down significatively the score mean in Hamilton scale for the
      anxiety after 10-15 days of treatment. According to an intention analysis a
      therapeutic profit was got in the 76.7% of the sample depending on medical
      criteria and the 74.0% on patient criteria after 20-30 days of the treatment. The
      results obtained are discussed in terms of the sample characteristics.

PMID- 1983368
TI  - [XXXIst Congress of Stomatology and Maxillofacial Surgery. Marseille, 19-22
      September 1989].

PMID- 1983369
TI  - Two kinases mediate agonist-dependent phosphorylation and desensitization of the
      beta 2-adrenergic receptor.
AB  - Binding of the catecholamine agonists epinephrine and norepinephrine to the beta
      adrenergic receptor (BAR) rapidly activates adenylate cyclase via the stimulatory
      guanine nucleotide regulatory protein Gs, and results in rises in cellular levels
      of cAMP. However, continuous exposure to these agonists leads within minutes to a
      dampening of the enzymatic response. Both in vivo and in vitro studies have
      implicated agonist-induced phosphorylation of BAR in this process. These results
      include the isolation of a novel beta-adrenergic receptor kinase (BARK), which
      has been shown to preferentially phosphorylate receptors that are occupied by
      agonist when assessed in vitro. Recent studies in our laboratory have examined
      the desensitization process in intact cells to determine where on the receptor
      molecule functionally relevant phosphorylation occurs, and to identify the
      kinase(s) involved. In one set of studies, site-specific mutagenic techniques
      with the cloned gene for the human beta 2-adrenergic receptor were utilized to
      delete putative sites of phosphorylation by BARK and/or the cAMP-dependent
      protein kinase (PKA). Following expression of the mutated receptors in mammalian
      cells, the cells were challenged with different concentrations of agonist for 10
      15 min and the functional and phosphorylation properties of the mutant receptors
      were then assessed. In another set of studies human A431 cells were permeabilized
      with low concentrations of digitonin and treated with selective inhibitors of
      both BARK and PKA. The cells were then exposed to desensitizing concentrations of
      agonist, and similar measurements performed. Taken together, the results from
      both sets of studies suggest that exposure of cells to low (nanomolar)
      concentrations of agonist leads to phosphorylation of the receptor on one or both
      consensus sites for PKA, and that the predominant effect of this phosphorylation
      on the adenylyl cyclase response is a loss in sensitivity of the receptor to
      further stimulation by the agonist. In contrast, exposure of cells to higher
      (micromolar) concentrations of agonist leads to BAR phosphorylation by both PKA
      and BARK, the latter on the carboxyl terminal region of the receptor.
      Phosphorylation of the receptor by both kinases appears to be required for the
      full desensitization effect seen with the high concentration of agonist, which
      includes both losses in sensitivity and in the maximal responsiveness of the
      adenylyl cyclase response upon subsequent challenge with the agonist. Such a dual
      kinase control of BAR phosphorylation may have important implications for
      understanding the regulation of desensitization under different physiological
      circumstances.

PMID- 1983370
TI  - Hepatoprotective and immunological effects of antioxidant drugs.
AB  - The hepatoprotective and immunomodulatory effects of silymarin and amino
      imidazole-carboxamide-phosphate were studied in 40 patients with alcoholic
      cirrhosis of the liver in a one-month double-blind clinical trial. Treatment with
      either of the drugs normalized the elevated levels of aspartate aminotransferase,
      alanine aminotransferase and serum bilirubin, markedly reduced the high level of
      gamma-glutamyl transferase, increased lectin-induced lymphoblast transformation,
      decreased the percentage of OKT8+ cells and suppressed lymphocytotoxicity. None
      of these changes occurred in the placebo-treated group. Thus, the
      hepatoprotective effects of silymarin and amino-imidazole-carboxamide-phosphate
      in alcoholic cirrhosis can partly be attributed to the immunomodulatory activity
      of the drugs.

PMID- 1983371
TI  - High-level expression of P-glycoprotein and 85 kD protein as assessed by flow
      cytometry and immunocytochemistry in leukemias and malignant lymphomas.
AB  - Acquired resistance developed after chemotherapy is characterized by lower
      sensitivity to anticancer agents. We utilized two monoclonal antibodies (MABs):
      MRK16 which recognized 170 to 180 kD P-glycoprotein and MRK20 which recognized 85
      kD protein, to investigate the frequency of multidrug-resistant cancer cells
      appearing during treatment of 23 cases of leukemias and 27 cases of malignant
      lymphomas. The reactivities of these MABs with lymphocytes and blastic cells were
      examined by flow cytometry and immunocytochemistry. The following findings were
      obtained. First, among 50 cases, increases in MRK16-reactive cells and MRK20
      reactive cells were noted in 17 cases (34%) and 28 cases (56%), respectively.
      Second, the increase of MRK16-positive cells in three cases and the increase of
      MRK20-positive cells in two cases were correlated with dosages of the
      corresponding anticancer drugs used. Although we investigated the total amounts
      of anti-cancer drugs used, we were not able to detect exactly when P-glycoprotein
      recognized by MRK16 and the 85 kDa protein recognized by MRK20 appeared in these
      resistant cells during treatment. More cases will be required to investigate the
      significance between treatment and reactivity of MRK16 or MRK20 with leukemia or
      lymphomas cells.

PMID- 1983372
TI  - Recent developments in the treatment of congestive heart failure.

PMID- 1983373
TI  - [Current advances in the physiopathology of primary motility disorders of the
      esophagus].
AB  - The authors review the recent literature about the classification of primary
      motor disorders of the oesophagus: achalasia, diffuse oesophageal spasm,
      nutcracker oesophagus, hypertensive lower oesophageal sphincter and non-specific
      intermediary disorders. In fact these motility disorders belong to a spectrum of
      diseases closely related, with chronological transformation of a specific
      disorder to another one or to intermediary disorders. Most of the recent
      pathophysiological research concerned primary achalasia, secondary achalasia
      syndromes being a kind of experimental model. These studies point to a
      morphological or functional deficiency of postganglionic nerves inhibiting the
      lower oesophageal sphincter (LOS) through noncholinergic nonadrenergic
      neurotransmitters. Recent advances in the treatment of achalasia and other
      motility disorders are not yet based on these findings. Although calcium channel
      blockers, like nifedipine, lower LOS basal pressure, they are not very useful on
      long term relief of symptoms of achalasia. Pneumatic dilatations or cardiomyotomy
      still remain the best methods of treatment of this disease.

PMID- 1983375
TI  - [Modulation of norepinephrine release in sympathetic nerve endings in renal
      hypertensive dogs].
AB  - Experimental renal hypertensive and normal dogs with femoral arteries constantly
      perfused were studied. Cocaine was used to block the presynaptic norepinephrine
      (NE) reuptake and tyramine to initiate the release of NE in sympathetic nerve
      endings. NE spillover and infusion pressure were measured under basic conditions
      and during intraarterial infusion of cocaine, tyramine and in combination with
      alpha 1 and alpha 2 adrenoceptor antagonists. The extent of NE spillover increase
      induced by infusion of tyramine, the increased infusion pressure by cocaine and
      tyramine, and the reduced infusion pressure by prazosin were all greater in
      hypertensive dogs than those in normal dogs, but adrenoceptor antagonist idazoxan
      further increased tyramine-induced NE spillover in normal dogs only. It was
      suggested that reduced-regulation of presynaptic alpha 2 adrenoceptors to NE
      release and increased responsiveness of postsynaptic alpha 1 adrenoceptors to NE
      were present in hypertensive dogs.

PMID- 1983376
TI  - Recovery from brain damage: behavioral and neurochemical approaches. Satellite
      symposium of the XXXI International Congress of Physiological Sciences (IUPS). 4
      7 July 1989, Warsaw, Poland.

PMID- 1983374
TI  - [Therapeutic strategy in the treatment of gastroesophageal reflux].
AB  - Management of gastro-oesophageal reflux disease depends on the importance
      attached by the physician to symptoms and to risk of complications, ie:
      stricture, haemorrhage, operation- and drug-hazards. A patient who suffers rarely
      and during short periods could require dietary and postural recommendations and
      the use of the following drugs: antacids, alginates, prokinetic agents and/or H2
      receptor antagonists. We consider that the rarity of stricture rules out the
      necessity of any change in management, whether or not erosive oesophagitis is
      observed at endoscopy. Most patients are treated with these drugs. On the other
      hand, when symptoms are frequent and occur daily and especially at night and when
      H2-receptor antagonists fail to relieve the pain, a more potent drug such as
      omeprazole is to be administered. The same applies to patients running the risk
      of haemorrhage resulting from anticoagulant coexisting therapy, the later
      condition requiring the lesions to be healed and relapse prevented. In the long
      run, the choice between a drug (H2-receptor antagonist or omeprazole) taken daily
      and surgery can be debated. Even when a stricture is present surgery is no longer
      necessary due to failure of conservative management. The decision depends on the
      operation-linked risks relative to the patient's condition and on his or her
      compliance to daily drug-administration. Respiratory or ENT complications are
      often difficult to alleviate by H2-receptor antagonists and may need to be
      treated with omeprazole.

PMID- 1983377
TI  - Neurotransmitters in hepatic encephalopathy.
AB  - The pathogenesis of hepatic encephalopathy (HE), a neuropsychiatric disorder
      resulting from liver failure, is still a matter of debate. Recently attention has
      been focused on brain neurotransmitters. The accumulating evidence indicates that
      the imbalanced metabolism and turnover as well as the altered functions of
      neurotransmitters (dopamine, noradrenaline, serotonin, GABA) and false
      neurotransmitters (phenylethanolamine, octopamine, synephrine) may be of high
      importance in the pathomechanism of HE. Our data permit adding histamine (HA) to
      the multifactorial pathogenesis of HE. The enhanced rate of histidine influx into
      the brain following portocaval anastomosis and a dramatic increase in the HA
      content in the hypothalamus may suggest the involvement of HA in the
      symptomatology of hepatic encephalopathy.

PMID- 1983378
TI  - Ganglioside-mediated protection from glutamate-induced neuronal death.
AB  - Glutamate, an excitatory amino acid (EAA), plays an important role in neuron to
      neuron signaling by binding to specific receptors. When, during neuronal firing,
      quanta of glutamate are released from the nerve terminal, they interact with the
      receptors for a few milliseconds and, thereafter, glutamate is promptly cleared
      by appropriate mechanisms. The neurotoxic action of glutamate arises from its
      capacity to trigger a pathophysiological chain of events when it acts
      continuously and abusively on its receptors (e.g., during cerebral edema
      associated with trauma, ischemia, stroke). In primary cultures of cerabellar
      granule neurons the abusive stimulation of EAA receptors by glutamate amplifies
      pathologicaly two early intracellular signals: free cytosolic Ca++ and the
      translocation of protein kinase C (PKC) from cytosol to neuronal membrane. Both
      of these signals persist unabated even after removal of glutamate from the
      incubation medium. Natural gangliosides and their semisynthetic derivatives
      protect neurons from glutamate toxicity by blocking the consequences of receptor
      abuse but they leave physiological responses to glutamate unaffected; hence they
      represent a prototype of a "receptor abuse dependent antagonist" (RADA).

PMID- 1983379
TI  - New restriction fragment length polymorphism (probe E9) reveals the highest
      linkage disequilibrium in Italian CF patients.
AB  - We report that the allele distribution for RFLP's flanking the CF gene differs
      between patients with and without pancreatic insufficiency. The present study
      confirms this difference. In both classes the linkage disequilibrium (LD) is
      highest with the RFLP revealed by probe E9. The haplotype distribution identified
      by these RFLP's can be used for indirect carrier detection.

PMID- 1983380
TI  - Preliminary results on cystic fibrosis haplotypes from patients diagnosed in
      Odessa.
AB  - Two RFLP's closely linked to the CF gene (KM.19/PstI and XV-2c/TaqI) have been
      analysed in a sample of CF families in which one or more affected children had
      been diagnosed by the CF Centre of Odessa. The most frequent haplotype in CF
      chromosomes (2-1) is the same observed with higher frequency in other
      populations. If confirmed on a larger sample of CF patients from the USSR, this
      result might be indicative of heterogeneity of mutations present in the Soviet
      population.

PMID- 1983381
TI  - Distribution of RFLP haplotypes in CF in relation to clinical course.

PMID- 1983382
TI  - First trimester diagnosis of cystic fibrosis with linked DNA probes.
AB  - In late 1985 the cystic fibrosis (CF) gene was located to chromosome 7, at 7q
      22/31. Several restriction fragment length polymorphism (RFLP) markers are
      closely linked to the CF gene. These markers permit accurate first-trimester
      prenatal diagnosis based on analysis of chorionic villus DNA by studies of
      families with one or more affected children. In our laboratory 13 families at
      risk of having a child with CF have been counselled by the use of linked DNA
      probes: xV-2c; pCS.7; Met H; Met D; pJ3.11; KM 19. In all cases one or more of
      the mentioned probes were sufficiently informative to allow first-trimester
      prenatal diagnosis. In four of the 13 families tested prenatal diagnosis have
      been performed.

PMID- 1983383
TI  - [Different aspects of the cognitive activities of patients with schizophrenia.
      IV. Imbalance between assertions and negations].
AB  - Not being able to equilibrate affirmations and negations, the schizophrenic
      patient accedes only exceptionally to the majoring equilibrations of the second
      and third levels. In the logico-mathematic field, he does not approach the
      constructive synthetizing generalisations of reasoning. Lacking reflective
      abstraction, he cannot balance his logico-mathematic reasoning and differentiate
      what is structurally possible from what is materially possible, thus explaining
      his inaccessibility to perceive logic necessities, contrasting with the
      certainties of his delirium. In the logico-experimental domain, he reaches only
      rarely clause reasoning generalisation, and relapses regularly to the level of
      inappropriate generalisations of the extended inductive type. It is useless to
      try to find the "primum movens" of his difficulties, either in his imbalance
      assimilation/accommodation, or in his impossibility to see his contradictions, or
      even in his incapacity to equilibrate affirmations and negations. The majoring
      equilibrations, of which he is unable, are the functional expression of
      structures which do not follow the linear causality of Laplace's determinism but
      the circular causality characteristic of teleonomic processes. After a month of
      neuroleptic treatment, the decompensated schizophrenic's balance between
      assimilation and accommodation is partially restored.

PMID- 1983384
TI  - International symposium on the girl child in Asia.

PMID- 1983385
TI  - Advances in nonoperative treatment of genuine stress incontinence.

PMID- 1983386
TI  - Antibodies as drug carriers for solid tumors: evaluation of drug-anti-SSEA-1
      conjugates in the treatment of teratocarcinoma.

PMID- 1983387
TI  - Structure and function in neurology and psychiatry.
AB  - In the 19th century the triumphs of neuropathology and the clinico-anatomical
      method led to the evolution of neurology as a separate 'organically' based
      discipline associated with the concept of functional localisation. At the same
      time the growth of psychodynamic psychiatry contributed to the progressive
      separation of the two disciplines, with neuropsychiatry sitting uneasily in the
      middle. Psychiatrists are now showing increasing interest in the structure and
      function of the nervous system, but are having difficulty in integrating their
      findings into 'functional' diseases. This may be because disorder of function in
      the nervous system is much more complex than previously envisaged. The function
      of the nervous system is profoundly affected by psychological and social factors.
      The view that neurology is wholly 'organic' and synonymous with structural
      disease of the nervous system is fallacious. Neurological patients have complex
      dynamic disorders of function in the nervous system whether or not structural
      disease is present.

PMID- 1983388
TI  - Overexcitement and disinhibition. Dynamic neurotransmitter interactions in
      alcohol withdrawal.
AB  - In alcohol withdrawal, abnormalities occur in a number of neurotransmitter
      systems: there is reduced inhibitory function, and increased activity of
      excitatory systems. The former, indicated by reduced GABA and alpha-2
      adrenoceptor activity, acts in conjunction with, and is exacerbated by, the
      latter, which itself may be due to the potentiation of NMDA activity by depletion
      of magnesium, and overactivity of catecholaminergic and CRF neurones. These
      dysfunctions produce immediate effects and may also contribute to the long-term
      changes in brain excitability by a kindling-like process. It is possible that
      early and active treatment may oppose this process. Present strategies for
      treatment of alcohol withdrawal enhance GABA and alpha-2 inhibitory, or reduce
      excitatory, mechanisms. Future possibilities include the use of CRF and/or NMDA
      antagonists.

PMID- 1983389
TI  - Obstetric complications, the putative familial-sporadic distinction, and tardive
      dyskinesia in schizophrenia.
AB  - Obstetric complications were more common in the histories of those schizophrenic
      outpatients without a family history of psychiatric disorder, and were associated
      with an earlier onset of their illness. Those patients with tardive dyskinesia
      were more likely to have a family history of psychiatric disorder, less likely to
      have experienced obstetric complications, and showed greater cognitive deficit.
      Obstetric complications should be considered in juxtaposition with genetic
      factors in evaluating the putative familial-sporadic distinction in
      schizophrenia. Additionally, familial/genetic factors appears to contribute to
      vulnerability to tardive dyskinesia.

PMID- 1983390
TI  - Predictors of improvement in tardive dyskinesia following discontinuation of
      neuroleptic medication.
AB  - Forty-nine chronic psychiatric out-patients (ten were schizophrenic) with tardive
      dyskinesia (TD) were examined monthly for a mean of 40 weeks (range 1-59 months)
      after discontinuation of neuroleptic medication. Complete and persistent
      reversibility of TD was rare (2%), but many patients showed noticeable
      improvement in movements within the first year of discontinuation, which was
      sometimes interrupted by psychological relapse. Using three separate outcome
      measures and appropriate model-fitting techniques for each, we identified several
      predictors of improvement in TD, including an affective or schizoaffective
      psychiatric diagnosis, chronic (over 20 years) psychiatric illness, being
      employed, younger age, and increased neuroleptic dose before discontinuation.
      Consistent findings emerging from these analyses suggest that the type and
      history of psychiatric illness affect the course of TD.

PMID- 1983391
TI  - Neuroleptic malignant syndrome.

PMID- 1983392
TI  - WHO consensus statement.

PMID- 1983393
TI  - Three new non-sedative antihistamines: worth keeping an eye open for.

PMID- 1983394
TI  - Beta blockade after acute myocardial infarction.

PMID- 1983395
TI  - Xamoterol--more trouble than it's worth?

PMID- 1983396
TI  - Tensile strength of the solder joints of some recasted dental alloys.

PMID- 1983397
TI  - [Current concepts of the effects of neuroleptics].

PMID- 1983398
TI  - [Molecular pharmacology in the therapeutic service. I. Benzodiazepines: quid
      novi?].

PMID- 1983400
TI  - The past, present, and future of opioid anesthetics.

PMID- 1983399
TI  - Persistent bradycardia with episodic sinus arrest after sufentanil and vecuronium
      administration--successful treatment with isoproterenol.

PMID- 1983401
TI  - Case 2--1990. A 14-month-old with aberrant beta-adrenoceptor responses after
      complete tetralogy of Fallot repair.

PMID- 1983402
TI  - Cardiac arrest and aortic stenosis.

PMID- 1983403
TI  - Sufentanil-midazolam anesthesia for coronary artery surgery.
AB  - The combination of benzodiazepines and high-dose narcotics has been reported to
      produce hypotension in patients undergoing coronary artery surgery. This study
      was performed to evaluate the cardiovascular effects of lower doses of the
      narcotic sufentanil administered with the benzodiazepine midazolam. Thirty adult
      patients with good ventricular function undergoing elective coronary
      revascularization received sufentanil, 2.5 micrograms/kg, and midazolam, 0.1
      mg/kg, followed by infusions of sufentanil, 0.7 to 1.5 micrograms/kg/h, and
      midazolam, 0.07 to 0.15 mg/kg/h. Overall, stable hemodynamics were achieved
      before and after cardiopulmonary bypass (CPB). Patients who were not receiving
      preoperative beta-adrenergic blockade (n = 15) had increases from baseline heart
      rate and rate-pressure product after sternotomy, during aortic dissection, and
      after CPB that were not clinically significant. Five patients developed
      hypertension (increases greater than 20% over the baseline value), which was
      controlled with additional sufentanil or a vasodilator. Hypertension requiring
      vasodilator therapy did not occur in patients taking beta-adrenergic blockers.
      Blood pressure decreases exceeding 20% of the baseline value did not occur. Two
      of 15 patients receiving beta-blockers, versus 3 of 15 not receiving beta
      blockers, developed ischemic electrocardiographic changes before CPB (NS); one of
      these patients without beta-blockade had a postoperative myocardial infarction.
      The results of this study show that the infusion of low doses of sufentanil with
      midazolam provides a hemodynamically safe and stable anesthetic for coronary
      artery surgery and avoids the hypotension seen when a high-dose narcotic is
      combined with a benzodiazepine.

PMID- 1983404
TI  - Cardiovascular effects of pancuronium, vecuronium, and atracurium during
      induction of anesthesia with sufentanil and lorazepam for myocardial
      revascularization.
AB  - The hemodynamic effects of three commonly used muscle relaxants, pancuronium,
      vecuronium, and atracurium were investigated during induction of anesthesia with
      sufentanil and lorazepam in patients undergoing coronary artery bypass surgery.
      Direct hemodynamic variables were recorded, and indirect parameters were
      calculated using standard formulae. Changes in heart rate differed with the three
      muscle relaxants. Pancuronium increased the heart rate whereas vecuronium and
      atracurium produced a decrease 5 minutes after induction (P less than 0.05). No
      differences were found in any other parameter during the study. A slow induction
      with sufentanil, lorazepam, and any of the three muscle relaxants was shown to
      minimize the hemodynamic changes.

PMID- 1983405
TI  - Free and total lidocaine levels in cardiac surgical patients.
AB  - A lidocaine bolus of 2 mg/kg has been shown to decrease the incidence of
      ventricular fibrillation in cardiac surgical patients during reperfusion
      following aortic cross-clamp release (CCR). In an effort to extend this effect
      into the immediate postoperative period, many centers routinely administer a
      prophylactic lidocaine infusion for the first 12 to 24 hours after surgery.
      Sequential total serum lidocaine levels were measured over 6 hours in 28 adult
      cardiac surgical patients without liver, kidney, or respiratory disease, and free
      serum lidocaine levels were measured in 15 of these patients. In addition,
      pharmacokinetic data were collected and analyzed in 8 of these patients. Each
      patient received a lidocaine bolus of 1.5 mg/kg and an infusion at 2 mg/min
      immediately before CCR. Serum levels were determined just before CCR, and at 10,
      20, 30, 60, 120, 240, and 480 minutes after CCR. More than 50% of patients had
      subtherapeutic total serum lidocaine levels from 20 to 120 minutes after CCR, but
      free lidocaine levels remained within the therapeutic range. No patient showed
      malignant ventricular dysrhythmias during the study. The results suggest that (1)
      it may be misleading to estimate free lidocaine concentration based on total
      lidocaine levels; and (2) free drug is the moiety responsible for lidocaine's
      antiarrhythmic effect.

PMID- 1983406
TI  - Case conference 3--1990. Two patients develop some signs and symptoms of
      malignant hyperthermia during cardiac surgery with cardiopulmonary bypass--is it
      the real thing.

PMID- 1983408
TI  - Influence of temperature on in vitro metabolism of esmolol.
AB  - Esmolol has been used to improve hemodynamic stability during sternotomy and
      aortic manipulation for coronary artery bypass graft surgery. In order to
      investigate the alterations of esmolol metabolism by hypothermic cardiopulmonary
      bypass (CPB), the effect of temperature on the metabolism of esmolol in vitro was
      determined. Samples of human whole blood were combined with esmolol solution (50
      micrograms/mL in 0.9 mol/L NaCl) and incubated at 4 degrees C, 15 degrees C, 25
      degrees C, and 37 degrees C. Aliquots were sampled at 1, 5, 10, 15, 30, 60, and
      120 minutes; esmolol concentration was determined using high-pressure liquid
      chromatography. There was a temperature-dependent decrease in the degradation of
      esmolol. The half-life for esmolol in human blood was 19.6 +/- 3.8 minutes at 37
      degrees C, 47 +/- 10.1 minutes at 25 degrees C, 152 +/- 46.6 minutes at 15
      degrees C, and 226.7 +/- 60.1 minutes at 4 degrees C. This study clearly shows
      marked reduction of esmolol metabolism with hypothermia possibly leading to
      persistent beta-adrenergic blockade following the discontinuation of CPB.
      Persistent beta-blockade may provide additional protection to the ischemic
      myocardium during hypothermic arrest and/or result in difficulty in weaning from
      CPB.

PMID- 1983407
TI  - Alpha-adrenergic agonist drugs, left ventricular function, and emergency from
      cardiopulmonary bypass.
AB  - The relationship between preoperative left ventricular (LV) dysfunction and the
      use of alpha-adrenoceptor agonists during weaning from cardiopulmonary bypass was
      studied in 102 patients undergoing coronary artery surgery. LV function was
      evaluated subjectively by examination of the 30 degree right anterior oblique
      left ventriculogram. Group 1 consisted of 75 patients with normal or mild
      impairment in LV function, whereas group 2 consisted of 27 patients with moderate
      severe LV dysfunction. Cardiovascular parameters were measured at baseline,
      during hypothermic bypass with the aorta clamped, during normothermic bypass
      after unclamping, and 1 and 15 minutes after separation from bypass. Thirty-seven
      patients in group 1 (49%) and 11 patients in group 2 (39%) required some form of
      inotropic and/or vasopressor support during weaning from bypass. Group 2 required
      significantly higher cumulative doses of phenylephrine after bypass compared with
      group 1 (1.69 +/- 0.70 mg, n = 9, v 0.24 +/- 0.04 mg, n = 27, P less than 0.05).
      Similarly, the dose of norepinephrine infusion in group 2 was 3.3 times that in
      group 1 (10 +/- 6 micrograms/min, n = 2, v 3 +/- 0.6 micrograms/min, n = 2, P =
      NS). The higher doses of alpha-adrenoceptor agonists required in patients with
      moderate-severe LV dysfunction may be due to differences in alpha-adrenoceptor
      agonist affinity and/or receptor density.

PMID- 1983410
TI  - The 1990 national meeting of the Italian Society of Gastroenterology. Ancona, 19
      21 September 1990.

PMID- 1983409
TI  - Italian Association for the Study of the Liver. XXIII annual meeting. Rome, May
      31-June 1, 1990.

PMID- 1983411
TI  - Report of the 3rd National Congress of the Italian Federation of Coloproctology.

PMID- 1983413
TI  - Long-term treatment for gastric and duodenal ulcer.
AB  - The histamine H2-receptor antagonists, cimetidine, ranitidine, famotidine and
      nizatidine are effective in promoting the healing of both gastric and duodenal
      ulcer. Unfortunately the recurrence rate after withdrawal of the therapy does not
      appear modified and many studies indicate an increased rate of relapse after
      antisecretory treatment. The difference between various H2-blockers in terms of
      duration of acid inhibition and then increasing in gastrin levels may play a role
      in explaining the phenomenon, the exception represented by the last H2-blocker,
      nizatidine. It is reasonable, therefore, to analyze the different therapeutical
      approaches proposed for ulcer relapse prevention, such as continuous maintenance
      therapy, seasonal on demand, intermittent, week-end therapy, association of drugs
      with different mechanisms of action, etc. Four categories of patients can be
      characterized both for gastric and duodenal localization: 1. Subjects with low
      rate of relapses, i.e. less than one each fifteen months; 2. Subjects with
      episodic relapses, i.e.; one or two per year; 3. Subjects with frequent relapses,
      i.e. more than three per year; 4. Subjects with complications (bleeding,
      perforation).

PMID- 1983412
TI  - Continuous intragastric pH monitoring: a real progress in the assessment of
      antisecretory drugs.
AB  - 24 hour intragastric pH recording by means of an indwelling minielectrode which
      is connected to an ambulatory apparatus is unquestioned in the assessment of the
      pharmacodynamic properties of potent antisecretory drugs. pH measurements
      obtained with this continuous monitoring have been shown to be more accurate than
      those provided by the traditional hourly nasogastric aspiration method. We used
      this technique to evaluate the effects on gastric acidity of placebo, ranitidine
      150mg, famotidine 20mg and nizatidine 150mg in fifteen patients with healed
      duodenal ulcer. These medications were orally administered at 22:00hr in a double
      blind fashion on four separate occasions at least one week apart. All H2-receptor
      blockers were more effective than placebo in suppressing both circadian (p less
      than 0.001) and nocturnal (p less than 0.0001) gastric acidity, while there was
      no significant difference between the effects of the three active agents in the
      same time periods. During morning hours (8:00-12:00) both ranitidine and
      nizatidine did not differ from placebo, and famotidine produced more acid
      inhibition than nizatidine (p less than 0.03). However, in the same period the
      percent of time spent above pH 4.0 was significantly superior (p less than
      0.00001) for both famotidine (33%) and ranitidine (14.2%) with respect to
      nizatidine (6%) and placebo (8.4%). Therefore, after bedtime dosing, the action
      of nizatidine is more confined to the nocturnal period than those of ranitidine
      and famotidine.

PMID- 1983415
TI  - Gastrin pathophysiology: antisecretory drugs.
AB  - The management of maintenance therapy in peptic disease (oesophagus, stomach,
      duodenum) with antisecretory drugs should keep in consideration the aspect of
      developing hypergastrinemia: gastrin exerts a throphic effect on gastric ECL and
      parietal cells. After a long term maintenance therapy (3-5) years) with
      ranitidine 150mg/die in a group of 55 patients affected by duodenal ulcer, 20% of
      them developed hypergastrinemia and gastric hypersecretion (evaluated after one
      week of drug withdrawal). The same 20% of the subjects showed increased relapse
      rates with respect to those who did develop the same gastrin/gastric acid
      increase.

PMID- 1983414
TI  - Long-term treatment of reflux oesophagitis.
AB  - Reflux oesophagitis is a chronic recurrent disease with high tendency towards
      relapse after medical healing. It has been calculated that after 6 months a
      symptomatic relapse may occur in about 45% of patients, while a recurrence of
      mucosal lesions ranges between 20 to 70%. The most important adverse factors
      affecting the likelihood of recurrence are: a) the daytime symptoms at time of
      healing and b) an impairment of both oesophageal body motility and LOS tonic and
      phasic activity. The available data show that the maintenance treatment with anti
      H2 at standard doses does not affect the spontaneous recurrence of the disease.
      Better results could be achieved with higher dosage, possibly tailored to the
      physiopathological characteristics of the patients.

PMID- 1983416
TI  - Long-term treatment with anti-secretory drugs: could it affect morphology and
      cell kinetics of gastric mucosa?
AB  - Drugs reducing gastric acid output are widely used and commonly considered free
      from relevant side effects. However, our knowledge on the consequences of long
      term anti-secretory treatment is still lacking. Several observations both, in
      animal models and in man, indicate that a decreased gastric acid output may lead
      modifications of several features of epithelial gastric cells. These alterations
      can be determined by different mechanisms. The drugs can raise plasma levels of
      gastrin, which possibly cause a proliferative stimulus on fundic mucosa.
      Moreover, some drugs showed a direct effect on cell proliferation. Finally,
      hypochlorhydria reduces the antibacterial power of gastric juice. In this
      environment, bacterial flora can overgrow and synthesize also the N
      nitrosocompounds. These observations suggest that prolonged treatments with
      powerful anti-secretory drugs should be carried out taking into account the
      hypothetical biological risk on gastric mucosa.

PMID- 1983417
TI  - International Workshop on Seminal and Sperm-Specific Proteins in honour of
      Professor Thaddeus Mann. Burg Staufenberg, Germany, September 7-9, 1989.

PMID- 1983418
TI  - Polyamines and transglutaminase actions.
AB  - Polyamines (putrescine, spermidine and spermine), secreted by the prostate gland,
      occur in high concentrations in the seminal fluid of many species, including man
      and rat. The physiological significance of seminal polyamines is still obscure,
      however. It has been postulated that polyamines may serve as amine donor
      substrates for transglutaminases (TGases), enzymes catalyzing protein
      crosslinking by the formation of gamma-glutamyl-lysine or bis(gamma
      glutamyl)polyamine cross-bridges. We have analyzed TGase-activities and polyamine
      content of the various rat prostate lobes and rat seminal vesicles. Highest TGase
      activities were observed in the coagulating gland (anterior prostate) and the
      dorsolateral prostate, whereas very little TGase activity was present in the
      ventral prostate gland. In contrast, polyamine concentrations were highest in the
      ventral prostate but low in coagulating glands. Seminal vesicles, and in
      particular seminal vesicle secretions, contained low polyamine levels and
      intermediate TGase activity. Levels of protein-bound polyamines, not extractable
      by perchlorid acid, did not correlate with TGase-activities in ventral prostate
      and coagulating glands, suggesting an extracellular rather than intracellular
      function of prostatic TGase and polyamines. The observation that Km-values of rat
      prostate TGase for all three polyamines (57-120 microM, using N,N-dimethylated
      casein as protein substrate) were well below seminal polyamine concentrations is
      compatible with a regulatory role of polyamines in the process of seminal clot
      formation.

PMID- 1983419
TI  - Inhibition of gastric acid secretion: advantages and risks in short and long-term
      treatment.
AB  - The administration of the currently available H2-blockers (at a dosage that
      induces only partial inhibition of the intragastric acidity) is effective in
      nearly all peptic ulcer patients in the short and long- term treatment. The
      benefits of more profound gastric acid inhibition (as achieved with omeprazole)
      in the short-term treatment of acid peptic diseases has been demonstrated in
      clinical studies. However, gastric acid has an important physiological role and
      the potential consequences of profound inhibition of gastric acid include
      intragastric bacterial colonization and hypergastrinaemia. Bacterial overgrowth
      of the stomach renders the gut more susceptible to enteric infection and another
      possible sequela of intragastric bacteria is the formation of N-nitroso compounds
      with carcinogenic potency. Hypergastrinaemia has a trofic effect on the gastric
      mucosa and gastric endocrine cells and, in animal, ECL cell hyperplasia and
      carcinoid formation has been observed as a result of high serum gastrin levels.
      So far, these potential risks have precluded the long-term administration of
      omeprazole.

PMID- 1983420
TI  - Powerful gastric acid inhibition: when is it justified?
AB  - Peptic ulcers fail to heal in up to 10% of patients after 8 weeks of therapy with
      H2-receptor antagonists largely owing to the multifactorial pathogenesis of the
      disease. Site-protective agents may heal the ulcers in many, but not all, of
      these non-responders. In ulcers which prove particularly refractory to therapy,
      only powerful gastric acid inhibition of the type best achieved with omeprazole
      is capable of healing most, and sometimes even 100% of patients in the short
      term. Powerful inhibition of gastric acid secretion proves clinically
      advantageous, in terms both of symptom relief and endoscopic lesions, in severe
      reflux oesophagitis, characterized, as it is, by erosive and ulcerative lesions.
      Strong inhibition of acid secretion is, of course, also indicated in Zollinger
      Ellison syndrome, the treatment of which has already been revolutionized by the
      use of H2-antagonists, usually given in very high doses, and appears to have made
      yet another step forward with the advent of omeprazole thanks to the particularly
      marked potency and duration of action of this benzimidazole derivative. Powerful
      inhibition of acid secretion thus seems possible both with high-dose H2
      antagonists and, most notably, with omeprazole. Though fully justified in certain
      classic conditions such as refractory ulcer, erosive-ulcerative oesophagitis and
      Zollinger-Ellison syndrome, massive antisecretory blockade would not appear to be
      suitable for indiscriminate use, especially long-term.

PMID- 1983421
TI  - Inhibition of gastric acid secretion and therapeutic results: is there any
      correlation?
AB  - The development of effective antisecretory drugs has risen the question of what
      is the ideal inhibition of gastric acid secretion in the treatment of peptic
      ulcer. Cimetidine, unlike the more recent H2-blockers and proton pump inhibitors,
      exerts antisecretory effects that are correlated to the blood levels of the drug.
      For this reason, therapeutic posologies were initially based on the
      pharmacokinetic features of the drug, while, more recently, direct measurement of
      intragastric acidity have assumed great relevance. Despite extensive research,
      the ideal level of gastric acid inhibition in the treatment of peptic ulcer has
      not been established. Greater healing rates are achieved by more potent
      antisecretory drugs and the duration of treatment appears to be also important,
      particularly to the healing of gastric ulcers. Whether the course of peptic ulcer
      disease is affected by the potency of the drug employed in the treatment of acute
      episodes has not been established.

PMID- 1983422
TI  - Site-and cytoprotective drugs in the short-term treatment of peptic ulcer. What
      is their current role?
AB  - Many endoscopically controlled comparisons with H2-blockers have widely
      documented that site- and cytoprotective drugs constitute effective and safe
      agents for the short-term treatment of gastric and duodenal ulcer. Their efficacy
      however, is counter-acted by the need for multiple daily administration which
      requires greater patient compliance. Due to its ability to eradicate Helicobacter
      pylori (HP) from the gastric antrum and retard relapses, colloidal bismuth may be
      the first choice anti-ulcer drug for those HP positive patients who do not accept
      continuous maintenance treatment after healing. A specific subgroup of duodenal
      ulcer patients who may particularly benefit from a short-term treatment with such
      agents (namely colloidal bismuth) are the non-responders to an 8-week course of
      H2-antagonists; conversely, actual evidence does not support the hypothetical
      superiority of such agents over H2-blockers in the treatment of cigarette smokers
      or chronic consumers of NSAIDs.

PMID- 1983423
TI  - Effects of gastrin and secretin on intestinal calcium absorption in the rat.
AB  - We studied the effect of physiological and supraphysiological plasma levels of
      gastrin and secretin on duodenal calcium absorption (CaA) in the growing rat.
      During infusion of either synthetic human gastrin 17 I (0.05, 0.1 or 0.25
      micrograms/kg BW h, i.v.), synthetic porcine secretion (0.06, 0.125 or 0.25 CU/kg
      BW h, i.v.) in vehicle (0.15% BSA in saline), or vehicle alone, duodenal lumen-to
      plasma flux, plasma-to-lumen flux and the net absorption of calcium were
      determined by in situ perfusion. While plasma gastrin- or secretin-like
      immunoreactivity rose to postprandial-like levels with increasing infusion doses,
      the bidirectional Ca fluxes, serum Ca, parathyroid hormone and concomitant
      urinary Ca excretion were not changed by any hormone infusion as compared with
      rats receiving intravenous vehicle only. We conclude that a physiological short
      term regulating role of these hormones in duodenal CaA is unlikely in the growing
      rat.

PMID- 1983424
TI  - Clinical aspects during therapy with the serotonin antagonist ketanserin.
AB  - Ketanserin, a selective S2-serotoninergic antagonist with an additional alpha 1
      receptor-blocking effect and a central component of action, represents a new type
      of antihypertensive drug. It decreases blood pressure by reducing total
      peripheral resistance. Cardiac output and heart rate remain practically
      unaltered. The antihypertensive effect of 2 x 20 to 2 x 40 mg/day corresponds to
      that of therapeutic doses of metoprolol, nifedipine, hydrochlorothiazide or
      captopril. The main subjective side effects are somnolence, dizziness and dryness
      of the mouth. No serious metabolic side effects have been observed. Ketanserin
      can lead to a prolongation of the QTc interval and therefore should not be given
      to patients with preexisting QTc prolongation, atrioventricular or sinoauricular
      block of higher degree or with severe bradycardia (less than 50/min). If a
      diuretic is to be prescribed simultaneously, it must contain a potassium-sparing
      component. Since its antihypertensive effect is more pronounced in older age,
      ketanserin should preferentially be given to patients over 60 years of age.

PMID- 1983426
TI  - Traumatic dental injuries in 3- to 13-year-old boys in Monterrey, Mexico.
AB  - The purpose of this retrospective study was to analyze, by age, the prevalence of
      traumatic injuries to primary and permanent incisors, and their distribution
      according to type in a group of boys from private schools in Monterrey, Mexico.
      The sample consisted of 1010 boys aged 3-13 years enrolled in 4 private schools
      in the city. Garcia-Godoy's classification for traumatic injuries was used. The
      prevalence of injuries was 28.4%; 72.2% of the 4-year-olds examined presented
      signs of traumatic dental injuries. Thirty-seven percent of the 11-year-olds
      examined had evidence of traumatic dental injuries. The most common type of
      injury in the primary and permanent dentitions was enamel fracture (58.5% and
      69.6%, respectively).

PMID- 1983425
TI  - New congenic rat strains for the separate study of MHC and non-MHC genetic
      effects in the development of diabetes in BB rats.
AB  - Diabetes in BB rats is genetically determined by at least two genes, the one gene
      mapping to the MHC, the other residing in the genetic background. In order to be
      able to study the role of MHC and non-MHC genes in diabetogenesis we have
      established rat strains which combine the diabetes-resistant LEW genetic
      background with the RT1u haplotype of diabetic BB rats (LEW.1BB) or carry the
      diabetes-resistant RT1 haplotype of LEW.1A rats on the diabetic BB genetic
      background (BB.1A). BB rats of two different sublines (BB/OK and BB/PhiK) were
      used for this purpose. In these rat strains diabetes relevant traits were studied
      longitudinally, the RT1 haplotypes were analyzed at DNA level and 18 non-MHC
      linked immunogenetic and enzyme loci were monitored. The results demonstrate the
      successful transfer of genes with potential relevance for diabetes development in
      BB rats.

PMID- 1983427
TI  - [Dentoalveolar trauma in children: retrospective study of 1,444 injuries].
AB  - This study comprises an analysis of traumatic dental injuries in children, from
      cases treated at the dental unit of the National Institute of Pediatrics over a
      period of seven years; a total of 1,444 traumatic injuries were seen in 809
      children. Data under study included; type, frequency and site of injury, sex and
      age of patients, maxilla more often predisposed, dentition most affected by
      trauma and, finally, time of the year in which more cases occurred.

PMID- 1983428
TI  - TcR-alpha and TcR-beta dialellic RFLPs in insulin-dependent (type I) Caucasian
      diabetic patients.
AB  - We studied the association of a T-cell receptor (TcR) beta restriction fragment
      length polymorphism (RFLP) and a new TcR-alpha RFLP with insulin-dependent (Type
      I) diabetes mellitus. This study is part of our effort to find new non-HLA
      disease genes involved in this chronic organ-specific autoimmune disease.
      Distribution of a 9.2 kb and a 10.0 kb diallelic TcR beta 2 RFLP was not
      different in diabetics and controls. A new TcR-alpha RFLP, which gave a 2.7 kb
      Hind III restriction fragment (A2 allele) was found with a frequency of 0.78 in a
      population of 78 IDDM patients, compared to 0.68 in 68 control subjects (X2 =
      3.62, p = 0.057). In 11 multiplex families studied, a high prevalence of the A2
      allele was also observed, but cosegregation with the disease was not seen. Our
      data suggest that a TcR beta 2 RFLP is not associated with the disease, whereas a
      particular T-cell receptor alpha germline RFLP (A2 allele) is increased in Type I
      diabetics although formal proof of linkage is lacking. HLA typing reconfirmed
      that the HLA-DR4 specificity and the DQ allele HLA-DQw8 are primary risk markers
      in insulin-dependent (Type I) diabetes mellitus.

PMID- 1983429
TI  - Malaria control: present situation and need for historical research.
AB  - A rapid review is made of the history of malaria control, calling attention to
      differences between the evolution of the technical concepts, the formulated
      strategies and their implementation. Particular emphasis is placed on the
      discussion of the present situation of the world malaria problem and the
      difficulties faced by many endemic countries in adopting a malaria control
      strategy, based on primary health care, while their services are vertically
      organized for the performance of routines, which are irrelevant for disease
      control. The present malaria control strategy recognizes local variability, but
      it is possible to identify a limited number of types of situations, likely to
      respond to similar approaches. The definition not only of the control approaches
      but also of their conditions of applicability will become more precise as
      experiences are accumulated and adequately documented from different types of
      epidemiological situations. It is postulated that historical research on the
      malaria control and public health approaches, with proper attention being given
      to their socioeconomic and political context, in the countries which succeeded in
      controlling endemic malaria, will make an important contribution to such a
      definition.

PMID- 1983430
TI  - A G protein-mediated inhibition of voltage-dependent Ca2+ influx in beta cells
      underlies somatostatin inhibition of insulin secretion.

PMID- 1983431
TI  - Complementation of genetic and functional defects in CD18-deficient lymphocytes
      by retrovirus-mediated gene transfer.

PMID- 1983432
TI  - Evidence for susceptibility of intrathymic T cell precursors to human
      immunodeficiency virus infection: a mechanism for T4 (CD4) lymphocyte depletion.

PMID- 1983434
TI  - Genetic selection for disease resistance and traits of economic importance in
      animal production.
AB  - Significant advances have been made in recent years in improving animal stocks by
      selective breeding. However, existing selection techniques still rely on
      laborious and time-consuming progeny-testing programs and often depend on
      subjective assessment of the phenotype. New techniques in molecular genetics are
      being developed, aimed at the isolation and identification of DNA markers linked
      to genes for economically important production traits and disease resistance.
      When available, these markers will provide animal breeders with an objective test
      system to identify, at birth or even earlier, animals carrying desirable genes.
      This review outlines some of these new techniques and how they may be applied to
      the animal industries. Consideration is also given to some of the recent advances
      in our understanding of the immune system and of possible mechanisms of genetic
      control of animal disease resistance or susceptibility. The current knowledge of
      major histocompatibility complex (MHC) and non-MHC associated disease
      resistance/susceptibility in domestic animals is summarised and mechanisms which
      may be responsible for these associations are presented. Genes that control such
      factors as macrophage activation, cytokines, cytokine receptors and gamma delta-T
      cell receptors are also presented as potential candidates for analysis in genetic
      disease association studies. Ultimately, the goal will be to identify genes or
      DNA markers which can be used to select for or to genetically engineer disease
      resistance and enhanced production traits.

PMID- 1983433
TI  - Controlled comparison of two anxiolytic benzodiazepines, cloxazolam and
      bromazepam.
AB  - The clinical activity and the tolerance of cloxazolam (4 mg/day), a new
      anxiolytic benzodiazepine, was compared to bromazepam (12 mg/day) in two parallel
      groups of 427 and 410 psychiatric outpatients, respectively. The duration of the
      study was 4 weeks with clinical assessments at inclusion and after 2 and 4 weeks
      of therapy by the Hamilton anxiety scale and visual analogue scales. While the
      Hamilton anxiety scale did not exhibit significant differences between the two
      benzodiazepines, visual analogue scales showed significant superiority of
      cloxazolam over bromazepam on psychological anxiety, somatic anxiety, depressed
      mood, and sleep, with a lack of significant difference related to the sedative
      effect, but less muscle-relaxant effect with cloxazolam than with bromazepam. The
      better efficacy and tolerance of cloxazolam compared to bromazepam was confirmed
      by the global assessments using visual analogue scales; moreover, a significantly
      larger proportion of patients in the cloxazolam group wanted to continue the same
      treatment.

PMID- 1983435
TI  - Control of genetic defects.
AB  - Recombinant DNA techniques offer the possibility of diagnosing genetic defects
      directly by analysing DNA itself. This is especially interesting for detecting
      carriers of recessive defects. In comparison with phenotypic screening with
      progeny testing or biochemical tests, DNA screening is independent of the time of
      gene expression and is not influenced by non-genetic effects. If the mutation
      causing the defect is known, alterations of DNA sequences can be identified
      directly as restriction fragment length polymorphisms (RFLPs) or with the use of
      allele specific oligonucleotides (ASO). DNA amplification with the polymerase
      chain reaction makes screening tests faster and more accurate. For most defects,
      the genetic basis is not known. Pedigree analysis with linked polymorphic DNA
      markers can be used to establish defect diagnosis. Linkage analysis can locate
      the chromosomal region of the gene responsible for the disease. Identification of
      the gene and the mutation in the defect allele finally will lead to direct DNA
      diagnosis. A dense linkage map with highly polymorphic genetic markers covering
      the entire genome will in future improve understanding of polygenic diseases.
      Increasing knowledge of the molecular genetics of human defects will promote DNA
      diagnosis in other species.

PMID- 1983437
TI  - New vistas on Mg in the 1st International Symposium on Metal Ions in Biology and
      Medicine.

PMID- 1983436
TI  - [Prevention of the 1st bleeding of esophageal varices: review of the literature
      and clinical experience].
AB  - The authors present a review of the literature on prophylactic sclerosis of
      esophageal varices in cirrhotics, taking as a starting point their personal
      experience. The natural history of varices and the criteria of their hemorrhagic
      risk are described; moreover are presented the results of the most important
      controlled studies of prophylactic surgery, sclerosis and beta-blocking drugs. In
      spite of the rather encouraging results after sclerosis at the long-term follow
      up and the promising aspects of beta-blocking agents, it is not felt to
      recommend, according to the literature, a routine application of prophylactic
      sclerosis, a procedure which should be reserved to leading centers in controlled
      studies.

PMID- 1983438
TI  - Proliferative capacity of senescent lymphocytes. II. Monoclonal antibody
      stimulation of mucosal and systemic lymphocytes via T cell activation molecules,
      CD3 epsilon, T cell receptor V beta 8 chain, and phosphatidylinositol-linked
      anchored receptors THY-1 and LY-6A.2/TAP.
AB  - The proliferative capacity of senescent mucosal and systemic lymphocytes was
      studied in response to monoclonal antibody (Mab) stimulation of T cell activation
      molecules, CD3 epsilon, V beta 8a chain of the T cell receptor (TcR-V beta 8),
      Thy-1, and Ly-6A.2/TAP. The percentage of positive cells, fluorescence
      intensities, and proliferative responses of lymphocytes from the spleen and
      mesenteric lymph nodes (mln) of individual C57BL/6J male mice were compared at 2,
      4, 12, 20, and 30 months of age. Mabs F23.1, 145-C11, Jij.10, and D7 were used to
      measure TCR-V beta 8a, CD3 epsilon, Thy-1, and Ly6A.2/TAP expressions,
      respectively. Optimal dose and kinetic studies were determined. There were no
      significant age-related changes in the percentage of splenic cells expressing CD3
      epsilon, TCR-V beta 8a, Thy-1, and Ly6A.2, as well as their fluorescence
      intensities on the cell surface as measured flow cytometry. For mln cells, the
      percentage of cells expressing TCR-V beta 8a, Thy-1, and Ly6A.2 did not
      significantly change with age. A significant age-related increase was found in
      the percentage of mln cells expressing CD3 epsilon. The fluorescence intensities
      of CD3 epsilon, TCR-V beta 8a, and Ly6A.2 expression on the cell surface of mln
      cells significantly increased with age. Mabs anti-TcR-V beta 8a and anti-CD3
      epsilon stimulation of splenic lymphocytes in culture for 3 days revealed a
      significant decline in proliferative responses after 12 months of age. When
      splenic cells were stimulated with Mab anti-CD3 epsilon in combination with
      optimal doses of phorbol myristate acetate (PMA) in culture for 3 days, there was
      a two-fold elevation in the proliferative response with a significant decline
      occurring after 20 months of age. Mab anti-TcR-V beta 8a and Mab anti-CD3 epsilon
      plus PMA stimulation of mln lymphocytes consistently revealed a significant
      decline in proliferative responses only after 20 months of age. Both splenic and
      mln cells showed a significant decline in proliferative responses to Mab anti-Thy
      1 stimulation after 12 months of age. There was no age-related change in the
      proliferation of splenic and mln cells to Mab anti-Ly6A.2 activation. These
      results indicate that the onset and rate of age-related decline in the
      proliferative capacity of lymphocytes after stimulation with Mabs anti-CD3
      epsilon and anti-TcR-V beta 8 chain changes much later and slower in the mln than
      those of the spleen.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1983440
TI  - Summary: the brain in 1990.

PMID- 1983439
TI  - [Experimental infection of the Guyanese zebu with Trypanosoma vivax].
AB  - The Guyanese strain of Trypanosoma vivax is pathogenic for the local Brahman
      zebu; the experimental infection of 19 one-year old cattle was followed by a
      moderate and transitory fever, a drop in packed cell volume (PCV) and a quick and
      marked weight loss of 10 to 17 kg one month after as compared to the 16 non
      infected animals. Other symptoms were associated with the parasitaemia:
      diarrhoea, swollen haematic glands on the neck and the flank, lachrymation,
      weakness. Despite a trypanocidal treatment injected one month post-infection, one
      animal died and the weight losses of others were not compensated for three months
      later. The particular susceptibility of weaning animals is discussed as well as
      its implications in the control of trypanosomosis.

PMID- 1983441
TI  - Presynaptic mechanisms in hippocampal long-term potentiation.

PMID- 1983443
TI  - Neuronal and network determinants of simple and higher-order features of
      associative learning: experimental and modeling approaches.

PMID- 1983444
TI  - Neuronal growth cone as an integrator of complex environmental information.

PMID- 1983442
TI  - Toward a representational hypothesis of the role of hippocampal synaptic
      plasticity in spatial and other forms of learning.

PMID- 1983446
TI  - Ultrastructural correlates of mechanoelectrical transduction in hair cells of the
      bullfrog's internal ear.

PMID- 1983445
TI  - Pioneer neurons and target selection in cerebral cortical development.

PMID- 1983447
TI  - Quantal analysis of excitatory synaptic mechanisms in the mammalian central
      nervous system.

PMID- 1983448
TI  - Cellular network underlying locomotion as revealed in a lower vertebrate model:
      transmitters, membrane properties, circuitry, and simulation.

PMID- 1983449
TI  - Short-term electrophysiological actions of insulin on Aplysia neurons:
      identification of a possible novel modulatory second-messenger mechanism.

PMID- 1983450
TI  - Immunology of HIV infection.
AB  - The goal of finding an effective vaccine against the human immunodeficiency virus
      (HIV) is hampered by our uncertainty of the mechanism(s) responsible for the
      pathogenesis as well as the lack of knowledge of protective mechanisms. The
      effects of HIV on the immune system are myriad and thus the truly significant
      manifestations of the pathology are difficult to dissociate from those more
      peripheral. In this article we will initially characterize the natural history of
      HIV infection which shows a chronic and perhaps inexorable course. The second
      part will deal with the immune response mounted against this assault and the
      final section is a discussion of the possible unfavorable consequences of the
      immune response that humans muster against this agent.

PMID- 1983452
TI  - 4th International Symposium on Pediatric Neuro-Oncology. November 14-16, 1991,
      Tokyo. Abstracts.

PMID- 1983451
TI  - The state of the testicle and the epididymis associated with exstrophy of the
      bladder in undescended testes.
AB  - In undescended tests, the large number of testicular dysplasias/hypoplasias and
      of that of the fusion abnormalities of the epididymis, and the joint occurrence
      of the two, can achieve even 50%. The frequency of the above anomalies were
      studied in undescended testes associated with exstrophy of the bladder. Bilateral
      undescended testes were observed in 5 out of 26 boys born with vesical exstrophy.
      In 3 of them bilateral orchiopexy had already been performed. In 5 of the 6
      operations intact testicles and intact epididymis were found. Fusion abnormality
      was observed only in one case, but the testicle was intact also in that case.
      This can be attributed to the fact that in exstrophy of the bladder, the
      testicles have failed to descend not due to the insufficient effect of fetal
      androgen, but due to anatomical causes. This is also supported by the fact that
      where the disorder of descension has been caused by mechanical factors, there was
      a much lower ratio of testicular-epididymal fusion abnormality.

PMID- 1983454
TI  - Facultative blood-feeding in the crabhole mosquito, Deinocerites cancer.
AB  - 1. Most of the female crabhole mosquitoes Deinocerites cancer Theobald entering
      bait traps had undeveloped ovaries. 2. Nearly half of the D. cancer females that
      were captured in bait traps, but denied blood, were gravid following a 1 week
      holding period; they developed relatively small egg clutches autogenously (mean =
      7.4 eggs per gravid female). 3. Although both parous and nulliparous D. cancer
      females were captured exiting from crabholes, only parous females were attracted
      to and collected in bait traps. 4. Much larger egg clutches (mean = 41.8 eggs per
      female) were produced anautogenously by mosquitoes that blood-fed on chickens. 5.
      All D. cancer females from field collected pupae developed eggs autogenously when
      allowed to mate and sugar feed in the laboratory. These mosquitoes produced an
      initial egg clutch with a mean size equivalent to that found in blood-fed, parous
      mosquitoes from bait traps. 6. In the field, mating and sugar feeding rather than
      blood-feeding seem to stimulate production of the initial egg clutch. 7. D.
      cancer blood-feeding appears to be delayed until after the first egg clutch has
      been laid; some parous crabhole mosquitoes are facultative blood feeders and can
      produce an egg clutch either with or without a blood meal.

PMID- 1983453
TI  - Sequence analysis of the human thymidine kinase gene promoter: comparison with
      the human PCNA promoter.
AB  - We report the sequence of 4264 nucleotides of 5' flanking sequence of the human
      thymidine kinase gene, a gene that is maximally expressed at the G1/S boundary of
      the cell cycle. The position of nucleotide sequences which can act as binding
      sites for trans-acting factors, Sp-1, AP-1/jun, AP-2, OTF-1 and CAAT box factors
      as well as other potential cis-acting sequences have been mapped. The
      organization of these cis-acting sequences in the promoter of the human PCNA gene
      (another gene that is maximally expressed at the G1/S boundary) are shown for
      comparison. The potential role that these sequences may play in the
      transcriptional regulation of these genes is discussed.

PMID- 1983455
TI  - Vector roles of Fennoscandian mosquitoes attracted to mammals, birds and frogs.
AB  - 1. Mosquitoes were sampled with five suction traps, from May to October 1983, at
      a forest site in south-central Sweden. 2. Twenty-three species of mosquitoes were
      identified among the total of 3108 females collected: 4% of them in an unbaited
      trap, 3% in a trap baited with two frogs, 24% with a guinea-pig, 28% with a hen
      and 40% in a trap baited with a rabbit. 3. The dominant species of Culicidae
      trapped were 39% Aedes communis (De Geer), 21% Ae. cinereus Meigen, 14%
      Coquillettidia richiardii (Ficalbi), 8% Ae. punctor (Kirby) and 4% Culiseta
      morsitans (Theobald). 4. Aedes annulipes (Meigen), Ae. cantans (Meigen), Ae.
      cinereus, Ae. communis and Ae. punctor were mostly attracted to the rabbit,
      whereas Culiseta morsitans, Culex pipiens L. and/or Cx torrentium Martini were
      strongly ornithophilic. 5. Based on these and previously published data the
      ecological and behavioural potential of the mosquitoes to transmit Sindbis,
      Inkoo, Tahyna and Batai viruses, tularaemia (caused by Francisella tularensis)
      and Ixodes-borne borreliosis (caused by Borrelia burgdorferi) in Fennoscandia is
      discussed. 6. The data support the hypothesis that Sindbis virus, which is
      enzootic in bird populations in Fennoscandia, is vectored between birds by Cx
      pipiens/torrentium and Cs. morsitans, and that abundant Aedes spp., particularly
      Ae. cinereus, which feed on both birds and mammals, are primary link vectors from
      infective birds to man and other mammals.

PMID- 1983456
TI  - Field studies on the potential of butanone, carbon dioxide, honey extract, 1
      octen-3-ol, L-lactic acid and phenols as attractants for mosquitoes.
AB  - Various combinations of six candidate attractants--butanone, carbon dioxide
      (CO2), honey, octenol, lactic acid and mixed phenols--were tested against natural
      populations of mosquitoes in Everglades National Park, Florida, U.S.A., using
      unlighted CDC-baited traps. With few exceptions, the attractancy of these
      candidate compounds to mosquitoes, when used alone, was less than that of CO2
      alone. The exceptions were that octenol and honey extract alone attracted larger
      numbers of Coquillettidia perturbans (Walker). Addition of lactic acid and/or
      octenol to CO2 increased trap collections of Aedes taeniorhynchus (Wiedemann),
      Anopheles atropos D. & K., and An. crucians Wiedemann by 1.4-13.8 times. Culex
      nigripalpus Theobald collections were increased 2.7 times by the addition of
      lactic acid, while the addition of octenol produced mixed results. Whereas the
      addition of lactic acid reduced collections of Cx (Melanoconion) spp., the
      addition of octenol generally increased collections. The opposite happened for
      Wyeomyia mitchellii (Theobald). For the biting midge, Culicoides furens (poey),
      octenol (1.6-23.4 x ) and phenol (2.7 x ) alone attracted larger numbers, and
      lactic acid alone attracted approximately the same numbers as CO2 alone. The
      combinations octenol + phenol and octenol + 200 ml/min CO2 increased C. furens
      collections c. 100 times over CO2 alone. The combination of octenol + CO2
      increased (1.6 x ) collections of the tabanid Diachlorus ferrugatus (Fabricius).
      Butanone appeared to decrease the trap collections of all species when combined
      with CO2 or octenol + CO2.

PMID- 1983457
TI  - Application of polar-orbiting, meteorological satellite data to detect flooding
      of Rift Valley Fever virus vector mosquito habitats in Kenya.
AB  - Measurements of green-leaf vegetation dynamics recorded by the advanced very high
      resolution radiometer instruments onboard National Oceanic and Atmospheric
      Administration satellites 7 and 9 were used to derive ground moisture and
      rainfall patterns in Kenya and monitor resultant flooding of mosquito larval
      habitats (dambos) likely to support Rift Valley Fever virus vector mosquitoes
      (Aedes and Culex spp.). Satellite-derived data from mid-1981 to December 1988
      have been analysed with corresponding rainfall, flooding and vector population
      data as they relate to Rift Valley Fever virus ecology. Single (7 x 7 km) and
      multiple grid-cell image analysis (200 x 300 km) in small localized areas and
      large geographical regions, respectively, of vegetation data were used to
      quantify the potential for flooding of mosquito breeding habitats. The ability to
      detect accurately parameters, such as ground moisture, that determine flooding
      could provide local officials with sufficient warning to allow for implementation
      of specific mosquito control measures before a disease outbreak.

PMID- 1983458
TI  - Effects of injection of selective adrenergic receptor antagonists into the
      lateral hypothalamic area on renal function.
AB  - Studies were undertaken to characterize the participation of specific alpha
      1,alpha-2 and beta adrenoceptors of the lateral hypothalamic area (LHA) in the
      urinary excretion of sodium and potassium. Alpha-1 and alpha-2 LHA receptors were
      shown to participate in the regulation of renal sodium and potassium excretion.
      The effects of noradrenaline microinjection (30 nmol in 1 microliter) into the
      LHA on urinary sodium excretion (UNaV) are blocked by previous injection of the
      alpha-1 antagonist prazosin (4 nmol in 1 microliter) from 3.22 +/- 0.25 to 0.59
      +/- 0.04 microEq min-1 100 g body weight-1. Pre-injection of yohimbine, an alpha
      2 antagonist (4 nmol in 1 microliter), synergistically potentiated the action of
      noradrenaline on UNaV (3.22 +/- 0.25 to 4.02 +/- 0.27 microEq min-1 100 g body
      weight-1) and on urinary potassium excretion (UKV) (0.70 +/- 0.08 to 1.15 +/-
      0.12 microEq min-1 100 g body weight-1). The beta-adrenergic blockers metoprolol
      (100 nmol in 1 microliter) and propranolol (100 nmol in 1 microliter) had no
      synergistic or antagonistic action on the sodium excretion fraction, suggesting
      that neither of these receptors is present in LHA. Our results indicate that
      natriuresis occurs even in the absence of changes in glomerular filtration rate
      and demonstrate an inhibitory natriuretic effect of an alpha-1 blocker (prazosin)
      injected into the LHA before adrenaline, while an alpha-2 antagonist (yohimbine)
      yielded a potentiating effect.

PMID- 1983459
TI  - [Multiple endocrine type II neoplasm].

PMID- 1983460
TI  - [Effect of increase of dietary polyunsaturated fatty acids (omega 6) on the
      hepatic glutathione content and gamma-glutamil transpeptidase activity in the
      kidney of rats].
AB  - The effect of feeding 24 to 52-days-old male rats of the Wistar strain, with
      beans diet deficient in sulfur-containing amino acids or supplemented with 0.3%
      DL-methionine and two corn oil concentrations, 2% and 20% (g/kg/diet), on the
      glutathione content (GSH) in liver, and on the renal gamma glutamyl
      transpeptidase (GGTP) (E.C.2.3.2.2) activity was studied. Results indicated that
      rats fed the bean diet with 2% corn oil decreased significantly the liver GSH
      content and GGTP renal activity. Supplementation with 0.3% methionine and/or the
      20% increment of the diet corn oil, significantly stimulated the liver GSH
      content and the transpeptidase activity in the kidney. It is postulated that the
      increase of polyunsaturated fatty acids, stimulated the GGTP activity as a way of
      increasing substrate bioavailability for synthesis de novo of liver GSH,
      necessary for the protection of the hydroperoxides formation, attributed to the
      increment of polyunsaturated acids at cellular level.

PMID- 1983461
TI  - Fibrinogen A alpha and gamma-chain dimers as potential differential indicators of
      atherosclerotic and thrombotic vascular disease.
AB  - Cross-linked fibrin(ogen) dimers are known to be elevated in the plasma of
      subjects with occlusive vascular disease, and are thought to be fibrin dimers.
      Immunoelectrophoretic analyses of the dimers, however, indicate that (1) they are
      predominantly fibrinogen rather than fibrin dimers, and (2) they contain cross
      linked A alpha-chains (A alpha-dyads) instead of the gamma-chain dyads that are
      rapidly formed by factor XIII during blood coagulation. Furthermore, the
      mobilities of the A alpha-dyads differ from the cross-linked alpha-chain products
      that accompany the gamma-chain cross-linking by factor XIII. Instead, the
      mobilities coincide with the distinct A alpha-dyads that are produced by tissue
      transglutaminase, an intracellular enzyme not normally present in plasma. The
      intimal fibrinogen deposits in atherosclerotic aortas also possess fibrinopeptide
      A and cross-linked A alpha-chains. Thus, both the plasma fibrinogen dimers and
      the intimal fibrinogen deposits appear to derive from the action of released
      tissue transglutaminase more so than factor XIII. It is proposed that, in the
      absence of other indications of cytolytic processes, the levels of A alpha-dyads
      in plasma reflect ongoing cellular injury accompanying atherogenesis. The extent
      to which gamma-dyads accompany the A alpha-dyads may signal progression of the
      disease to advanced stages in which ulcerations and occlusive lesions trigger
      thrombotic complications.

PMID- 1983462
TI  - Binding and covalent processing of fibrinogen by hepatocytes and endothelial
      cells.
AB  - In contrast to most plasma glycoproteins, asialofibrinogen and aglycofibrinogen
      manifest relatively normal in vivo survivals, suggesting that molecular
      determinants other than the carbohydrate may be involved in their catabolism. To
      analyse the metabolic properties of fibrinogen further, we analysed the
      interaction of normal fibrinogen with suspensions of rabbit hepatocytes or human
      umbilical vein endothelial cells. In so doing, we identified a novel type of
      fibrinogen - cell interaction which has the distinguishing characteristic of
      involving covalent transglutaminase-mediated fibrinogen cross-linking. In this
      report, we highlight some of the major distinguishing characteristics of this
      novel type of transglutaminase-mediated fibrinogen - cell interaction.

PMID- 1983464
TI  - Advances in platelet-activating factor research. XI International Congress of
      Pharmacology. IUPHAR Satellite Meeting. Paris, June 28-29, 1990. Abstracts.

PMID- 1983463
TI  - Delayed intermolecular gamma-chain cross-linking by factor XIIIa in fibrinogen
      Asahi characterized by a gamma-Met-310 to Thr substitution with an N-glycosylated
      gamma-Asn-308.
AB  - In an abnormal fibrinogen with gamma-Met-310 to Thr substitution accompanied by
      an extra oligosaccharide attached to gamma-Asn-308, factor-XIIIa-mediated
      intermolecular gamma-dimer formation of fibrin was found to be markedly delayed.
      The delayed gamma-dimer formation was not due to impaired fibrin polymerization
      because the fibrinogen gamma-chain also failed to be efficiently cross-linked by
      factor XIIIa. Since fluorescent amine was normally incorporated into the abnormal
      gamma-chain by factor XIIIa, we conclude that the abnormal molecules were unable
      to align their gamma-chains in an anti-parallel fashion because of
      inaccessibility of the molecules with a profoundly perturbed conformation near
      the carboxyl terminal region of the gamma-chain included in the D domain.

PMID- 1983465
TI  - Brief review: molecular mechanisms of neutrophil binding to endothelium involving
      platelet-activating factor and cytokines.

PMID- 1983466
TI  - Prognosis of permanent teeth in the line of mandibular fractures.
AB  - A total of 45 mandibular fracture patients with 54 teeth in the fracture line
      were evaluated retrospectively. One tooth in the fracture line was lost in the
      accident, 6 were extracted later and 47 could be saved (87%). At the follow-up
      examination 38% of the teeth were diagnosed to have pulp necrosis, which was
      found more frequently in the older patients and in cases in which the time
      elapsing between the injury and the follow-up was longer. Pulp necrosis was also
      more frequent in cases in which the fracture line ran through the apex or
      dislocation of the fracture parts existed after the injury.

PMID- 1983467
TI  - A six-year follow-up study of sports-related dental injuries in children and
      adolescents.
AB  - The records were analyzed of 106 patients with sports-related dental traumas
      treated in 1983 at the public oral surgery unit in Helsinki, Finland; 51 were
      examined six years after injury. The mean age was 11.8 years (range 7-24 years).
      The woman/man ratio was 1:3. In 39% of cases, the injuries had arisen from ice
      hockey or skating; 30% happened during school hours; 80% were uncomplicated crown
      fractures, concussions or subluxations. During the six-year follow-up, of 80
      teeth in 51 patients, root resorption was found in 6 teeth (7.5%), periapical
      lesions were noted in 2 teeth (2.5%), and obliteration of the pulp was seen in 4
      teeth (5%). Three teeth (3.7%) had suffered loss of vitality. The pulp had been
      extirpated in 13 of the traumatized teeth (16%). In all, 13.7% of the patients
      were found to have complications six years later. The results showed that long
      follow-up periods are needed after dental injury.

PMID- 1983468
TI  - Low affinity binding to glutamate receptor sites correlates with depolarizing
      responses induced by glutamate and quisqualate in striatal synaptoneurosomes.
AB  - In the present study, binding affinity of glutamate and quisqualate to striatal
      synaptoneurosome membranes in the guinea-pig was compared with concentration
      dependence of depolarizing responses induced by these agents. The displacement of
      radioactive glutamate from receptor binding site by unlabelled glutamate and
      quisqualate revealed a nonhomogeneous population of binding sites. A high
      affinity component of binding was observed with an inhibition constant of 0.04
      microM for glutamate and 0.45 microM for quisqualate, as well as a low affinity
      component with an inhibition constant of 10 microM for glutamate and 87 microM
      for quisqualate. Changes of the membrane potential in striatal synaptoneurosomes
      induced by glutamate and quisqualate were detected by measuring the absorbance of
      a potential sensitive cyanine dye. Glutamate and quisqualate induced constantly a
      depolarization in synaptoneurosome particles. Concentration-response curves
      showed that half-maximal depolarization was obtained with 10 microM glutamate and
      100 microM quisqualate. The comparison of the displacement data with the changes
      in the membrane potential in the present investigation indicate that in vitro
      glutamate and quisqualate depolarize striatal synaptoneurosome particles through
      low affinity binding to receptor site for glutamate.

PMID- 1983469
TI  - Microtopography of D1 dopaminergic binding sites in the human substantia nigra:
      an autoradiographic study.
AB  - The autoradiographic distribution of D1 dopaminergic binding sites was studied in
      the human ventral mesencephalon using the D1 antagonist [3H]SCH 23390. [3H]SCH
      23390 binding was characterized by a single class of sites with a Kd of 2.5 nM
      and a Bmax of 31 fmol/mg of tissue. The density of [3H]SCH 23390 binding sites
      was high in the substantia nigra, moderate in the ventral tegmental area and low
      in the peri- and retrorubral field (catecholaminergic region A8). Binding
      densities were similar in pars compacta and pars reticulata of the substantia
      nigra, except for a peak value of high [3H]SCH 23390 in the pars reticulata, at a
      level just ventral to a zone of hyperdensity of melanized dopaminergic neurons in
      the pars compacta. The anatomical organization of the human ventral mesencephalon
      was analysed on adjacent sections stained for acetylcholinesterase histochemistry
      and tyrosine hydroxylase, substance P, dynorphin B, somatostatin and methionine
      enkephalin immunohistochemistry, respectively. The similarity in distribution of
      [3H]SCH 23390 binding sites and substance P or dynorphin B immunoreactivity
      suggests that D1 binding sites are mainly located on the striatonigral
      projections. In accordance with these results: (1) the density of [3H]SCH 23390
      binding sites was reduced in the substantia nigra of a patient with Huntington's
      chorea, a disease associated with a degeneration of striatonigral neurons; (2)
      the density of [3H]SCH 23390 binding sites was unaffected in the substantia nigra
      of a patient with Parkinson's disease, a disorder characterized by a marked loss
      in nigral tyrosine hydroxylase-positive neurons. [3H]SCH 23390 binding sites
      showed a characteristic, heterogeneous distribution within the human ventral
      mesencephalon, confirming data obtained in other species. The preferential
      localization of D1 dopamine receptors on striatonigral projections in human brain
      suggests that pharmacological manipulation of these receptors modulates the
      activity of striatonigral pathways, thereby affecting the various outputs of the
      nigral complex.

PMID- 1983470
TI  - Neurotransmitters and neuropeptides within the mesencephalic trigeminal nucleus
      of the rat: an immunohistochemical analysis.
AB  - In order to determine which neurotransmitters and neuropeptides are utilized by
      the neurons of the mesencephalic trigeminal nucleus and by the fibres making
      synaptic contact with these primary sensory cells, we have set up an
      immunohistochemical study using antibodies against 17 major neurotransmitters and
      neuropeptides in the rat. Apart from some intracellular immunostaining for
      glutamate, no immunoreactivity to any of the tested neurotransmitters and
      neuropeptides could be detected inside mesencephalic nucleus of the trigeminal
      nerve neurons. Our immunohistochemical observations indicate that mesencephalic
      nucleus of the trigeminal nerve neurons receive input from various nerve fibres
      that appear to utilize serotonin, GABA, dopamine, noradrenaline (and likely
      glutamate) as transmitters. The innervation appeared randomly distributed over
      all mesencephalic nucleus of the trigeminal nerve neurons. The presence of
      substance P, cholecystokinin, vasoactive intestinal polypeptide, bombesin/gastrin
      releasing peptide, [Leu]enkephalin and neuropeptide Y observed in some fibres
      that contact with mesencephalic nucleus of the trigeminal nerve neurons,
      presumably reflect the co-existence of these peptides with one of the
      neurotransmitters.

PMID- 1983471
TI  - Calcitonin gene-related peptide and somatostatin immunoreactivities in the rat
      lumbar spinal cord: sexually dimorphic aspects.
AB  - The immunohistochemical distribution of calcitonin gene-related peptide and
      somatostatin in rat lumbar spinal laminae VII-X was investigated using the
      peroxidase-antiperoxidase technique. Within L1,2 laminae VII and X, calcitonin
      gene-related peptide and somatostatin fibers demarcate the location of
      preganglionic sympathetic neurons in a similar fashion in either sex but
      somatostatin is distributed in a sexually dimorphic manner in the lumbosacral (L5
      S2) spinal cord with the male rat containing more somatostatin fibers and neurons
      than females. Within the ventral horn (lamina IX), calcitonin gene-related
      peptide has a sexually dimorphic distribution. Calcitonin gene-related peptide
      varicose fibers are found within the sexually dimorphic male cremaster nucleus
      but are virtually absent in the female cremaster nucleus. Calcitonin gene-related
      peptide varicose fibers are nearly absent in the remainder of the male and female
      lamina IX: this area includes the other two known sexually dimorphic spinal
      motonuclei: the dorsomedial and dorsolateral nuclei. Virtually all motoneurons in
      the lumbosacral spinal cord which are not sexually dimorphic contain calcitonin
      gene-related peptide. However, calcitonin gene-related peptide containing
      motoneurons have a heterogeneous distribution within sexually dimorphic nuclei.
      Calcitonin gene-related peptide containing motoneurons within the male and female
      cremaster nucleus are extremely rare. Some motoneurons within the male and female
      dorsomedial and dorsolateral nuclei contain calcitonin gene-related peptide with
      the female dorsomedial and dorsolateral nuclei containing a greater percentage of
      calcitonin gene-related peptide-containing motoneurons (c. 50%) than males (c.
      20%). Somatostatin fibers are preferentially located in sexually dimorphic nuclei
      of either sex and are distributed in a sexually dimorphic manner within these
      nuclei with males containing a greater amount of somatostatin fibers than
      females. The amount of somatostatin immunoreactivity is most dense in the medial
      aspect of the dorsolateral nucleus, dense in the dorsomedial nucleus, moderate in
      the cremaster nucleus, and sparse in the lateral portion of the dorsolateral
      nucleus. In addition, a small column of motoneurons, between the dorsomedial and
      dorsolateral nuclei at the L5 level, is outlined by somatostatin fibers in
      females but is absent in males. Somatostatin containing motoneurons were not
      observed within the lumbar sexually dimorphic nuclei of either sex.

PMID- 1983473
TI  - [107th Congress of the German Society of Surgery. 17-21 April 1990].

PMID- 1983472
TI  - Isolation of the mouse Hox-2.9 gene; analysis of embryonic expression suggests
      that positional information along the anterior-posterior axis is specified by
      mesoderm.
AB  - It is rapidly becoming accepted that the vertebrate neural tube, in particular
      the hindbrain, develops into a segmented structure. After segment formation,
      cells in the neural tube do not cross segmental boundaries, and segment-specific
      gene expression is observed. However, it is not known what positional cues
      instruct the neural tube to express genes in this restricted manner. We have
      cloned a murine homeobox-containing gene, Hox-2.9, whose expression in the neural
      tube at E9.5 is restricted to a segment of the hindbrain known as rhombomere 4. A
      study of its expression pattern earlier in development revealed that prior to the
      start of neurulation (E7.5) Hox-2.9 is expressed within a posterior to the
      embryonic mesoderm that will participate in hindbrain formation. With the onset
      of neurulation, expression then becomes detectable in the neural plate as well,
      but only in the part that overlies the Hox-2.9-expressing mesoderm; it is not
      detected in the more anterior neuroectoderm that will form the future midbrain
      and forebrain. On the basis of these findings, we propose that the mesoderm is
      providing cues that serve to instruct the overlying neuroectoderm with respect to
      its position along the anteroposterior axis and that Hox-2.9 participates in or
      reflects this process. As neurulation continues and individual segments form, a
      second phase of expression is detected in the neural tube in which high levels of
      Hox-2.9 transcripts become restricted to rhombomere 4. Hox-2.9 expression is also
      detected in the developing branchial arch units of the hindbrain region, in a
      pattern that suggests to us that here, too, mesoderm is providing a localized
      signal that induces Hox-2.9 expression, in this case in endoderm of the pharynx
      and in superficial ectoderm. In general, we interpret the expression patterns of
      Hox-2.9 in the hindbrain region as suggesting that the specific mechanisms of
      pattern formation in mammals are fundamentally similar to those of amphibians and
      avians - i.e. anteroposterior positional information is acquired by mesoderm,
      mesoderm induces positional values within (neuro-) ectoderm and endoderm, and
      both events occur within a restricted window of time.

PMID- 1983474
TI  - [Preoperative localization in organic hyperinsulinism--useful or superfluous].
AB  - In our own patient material (n = 43) the percutane sonography had a sensitivity
      of 61.9%, the CT 73.3%, the angiography 66.6% and the PTP 76.9%. Intraoperatively
      95.2% of all insulinomas were palpable and the intraoperative sonography (IOS)
      had a sensitivity of 81.2%. In Germany all clinics except for one recommended a
      sonography and a CT and 83.8% an angiography prior to the first operation. A
      preoperative localization diagnostic is therefore not absolutely necessary, but
      may however be helpful in single cases.

PMID- 1983475
TI  - [Diagnosis and therapy of hyperinsulinism].
AB  - The diagnosis of hyperinsulinism in our 47 patients could be confirmed by
      clinical signs, blood sugar, insulin and C-peptide estimation. The preoperative
      localisation of the insulinoma was reached by angiography in 60%, by CT in 50%
      and by sonography in 10%. Intraoperative tumor localisation by measurement of
      incorporated P32 was effective in 70%. In 37 patients we enucleated one or more
      adenomas. In 5 children with Nesidioblastosis the left sided pancreas resection
      was performed. 5 patients with islet cell carcinoma were treated by
      duodenopancreatectomy and Streptozotocin. The longest survival time was 6 years.

PMID- 1983477
TI  - [Causes for adhesions in the abdomen].
AB  - About one-third of the intraabdominal adhesions that lead to mechanical obstacles
      are caused by inflammatory or congenital alterations. Two-thirds derive from
      previous surgical interventions. Besides foreign-body reactions to glove powder,
      textile fibres, intestinal contents, necroses, drugs, or drainages, the most
      important mechanism seems to be reduced fibrinolytic activity of the peritoneum.
      This prevents the disolution of fibrin adhesions and causes its fibrous
      organization. Local ischaemia caused by ligations and sutures is of decisive
      importance.

PMID- 1983476
TI  - [Pathophysiology and classification of adhesions].
AB  - The central issue in the pathophysiology of adhesions is the shift of the dynamic
      balance between fibrinolysis and fibrinogenesis to the side of fibrinogenesis.
      Permanent adhesions with the most varied morphology are formed by invasion of the
      fibrin network by fibroblasts and fibroid organization. Their classification by
      four degrees of severity is based on histological and morphological criteria.
      This classification has been shown useful and practicable for the objective
      examination and evaluation of relaparotomies in connection with expert opinion
      reports and animal experiments on adhesion research.

PMID- 1983478
TI  - [Surgical measures for preventing abdominal adhesions].
AB  - The extent of intraabdominal adhesions can be limited by reducing the degree of
      operative trauma. This may be achieved by: prevention of ischaemia, moistening of
      the peritoneal surface, gentle handling of tissue, and the use of thin atraumatic
      suture material. The most recent development, minimally invasive surgery, reduces
      the actual area of operative trauma, and possibly lessens the risk of
      postoperative adhesions. Should a re-laparotomy be indicated for complaints due
      to adhesions, the laparoscopic approach to adhesiolysis has increased in
      importance.

PMID- 1983479
TI  - [Prevention of adhesions by intraperitoneal administration of substances in
      abdominal interventions].
AB  - Various substances (saline solution, dextran, heparin, proteinase inhibitors,
      etc.) have been investigated to determine their influence on adhesion prevention,
      but until recently the results were controversial and lacked any implication for
      clinical use. The analysis of intraperitoneal plasminogen activating factor (PAA)
      and the fibronectin production rate of peritoneal macrophages promises new
      aspects of adhesion formation and prevention. The results of studies show a close
      correlation between ischemia/infection and the decrease of PAA as well as
      increased adhesion formation in patients (endometriosis) with increased
      fibronectin production by peritoneal macrophages.

PMID- 1983480
TI  - [Special aspects of abdominal adhesions in children].
AB  - Relaparotomy in children was necessary in 2.6% of 4902 cases because of adhesions
      (80% within 2 years). Adhesions can be differentiated histologically by the
      number of blood vessels. In the highly vascular adhesions arteries and veins are
      united in a common cord of connective tissue. Whereas the less vascular
      characteristically have a dense connective tissue rich in collagen. The number of
      capillaries distributed within the connective tissue varies. Some adhesions have
      a mixed tissue type of both tissues rich and poor in blood vessels. All adhesions
      are peripherally delimited by a different number of fibrous layers.

PMID- 1983481
TI  - [Special aspects of abdominal adhesions in gynecology].
AB  - Even minor adhesions in the oviduct or in the ovarial region may lead to
      infertility. In a controlled trial the adhesion status was documented in 103
      patients who underwent microsurgical operations for infertility. Solutions of (a)
      streptokinase/streptodornase, (b) hydrocortisone acetate or (c) Ringer's solution
      only were administered intraperitoneally as adhesion prophylaxis. During a
      control laparoscopy 1 week after the primary operation, newly formed adhesions of
      mainly intermediate extent were observed in about 10% of the patients. There was
      no significant difference in efficacy between the prophylactic treatment.

PMID- 1983482
TI  - [Prevention of adhesions in abdominal surgery. A dose finding study with
      streptokinase/streptodornase].
AB  - Measurement of intraperitoneal fibrinolytic activity on 50 patients having
      undergone abdominal surgery (four of them controls). Instillation of
      streptokinase/streptodornase (Varidase) into the abdominal cavity. Determination
      of total protein, plasminogen, antiplasmin, alpha 2 Mx-plasmin-complex,
      spontaneous fibrinolysis and fibrinolysis + activator at different points in time
      p.op. RESULTS: Intraperitoneal fibrinolysis may be stimulated by local
      substitution of a plasminogen activator (Varidase). Systemic effects are confined
      to a high dose. No impaired wound healing nor increased propensity to
      hemorrhaging occurred.

PMID- 1983483
TI  - [Side effects of adhesion prevention by fibrinolytic drugs--in vitro studies of
      resorbable suture material and fibrin glue].
AB  - Surgical threads of a variety of resorbable suture materials (Cat plain and Chrom
      Cat, Serag Wiessner, Polyglactin 910 and Polydioxanon, Ethicon and polyglycolic
      acid, Dexon) were incubated up to 7 days at 37 degrees C in Varidase-containing
      media (Lederle Cyanamid, 1000 IU/ml in 0.9% NaCl or citrated human plasma).
      Thereafter the knot-breaking strength remained within 90.0 and 108.2% of the
      respective control threads (incubation in Varidase-free media, n = 7, n.s.). The
      dose-dependent lysis of fibrin glue by Varidase is effectively inhibited by small
      amounts of aprotinin (15 KIU/ml as compared with 1000-3000 KIU/ml in routine
      application). The inhibitor is bound to the matrix and not readily eluted.

PMID- 1983485
TI  - [Animal experiment studies of amnion transplantation as peritoneal replacement].
AB  - In view of the favorable properties of the amniotic membranes as a peritoneal
      substitute, the following questions were posed: (1) Can the vitality of the
      amniotic epithelium be preserved by cryoconservation? (2) Which reactive changes
      occur in an intraabdominal amniotic graft? Animal studies gave the following
      findings. The vitality of the amniotic cells was not impaired by
      cryoconservation. A histiocytic demarcation zone developed on the membrane.

PMID- 1983484
TI  - [Etiopathogenesis of adhesions. Aspects of analysis of the literature 1888 to
      1989].
AB  - Despite surgical efforts over a century, peritoneal adhesions are still an
      unsolved problem. Pathogenetic aspects derived from an analysis of the literature
      (700 papers, 1888-1989) are discussed: Two basic mechanisms play a role.
      Inhibition of the physiological regeneration of mesothelial defects and
      depression of peritoneal fibrinolytic activity mainly by ischemia and
      inflammation. Fibrinolysis in due time prevents the fibrinous adhesions from
      being transformed into fibrous ones. - All prophylactic and therapeutic measures
      have to be evaluated regarding these factors.

PMID- 1983486
TI  - [Postoperative lung complications--introduction].
AB  - Intensive care patients suffer according to literature in 20-60% from pneumonia
      with a mortality up to 80%. The patient, operation and postoperative therapy
      influence its pathogenesis. Mechanical ventilation is a special risk factor.
      However, in this regard origin and sequelae may not be changed by mistake.
      Specifity of clinical and plain X-ray diagnosis is only 30-50%. Selective
      gastrointestinal decontamination, exactly monitored fluid balance, and physio-,
      and paintherapy seem to be valuable preventive measures.

PMID- 1983487
TI  - [Nosocomial lung infections. Epidemiology and problems of stress ulcer
      prevention].
AB  - The incidence of pulmonary complications in patients with tracheal intubation is
      17-25%. The mortality rate is considered to be between 50 and 81%. Aspiration of
      contaminated gastric fluid has been suggested to be a source of many of these
      complications. Gastric fluid contamination depends on the pH of the gastric fluid
      among other things. This results in a much higher incidence of nosocomial
      pneumonias in patients receiving H2-blockers (36%) or antacids and H2-blockers
      (38%) than placebo (8%) or sucralfate (10%). In contrast H2-blockers, antacids,
      omeprazole, pirenzepine and sucralfate show similar bleeding rates due to stress
      ulcers, but all are significantly lower than that of placebo. The routine
      application of prophylaxis for stress ulcer bleeding should nowadays be reserved
      for risk patients only. If necessary antimuscarinic drugs or sucralfate should be
      applied.

PMID- 1983488
TI  - [Diagnosis and monitoring of postoperative pulmonary complications].
AB  - There is no distinct difference between regular postoperative pulmonary changes
      and postoperative pulmonary complications (PPC). Beside the "classic" PPC,
      atelectases and bronchopneumonia, adult respiratory distress syndrome (ARDS) and
      barotraumas are becoming of increasing importance. A single examination allows
      the diagnosis of up to 60% of PPC. Only in 63% of cases of bronchopneumonia does
      the X-ray diagnosis agree with the necropsy results. The varieties of germs found
      in bronchial secretions and lung parenchyma, however, are not considerably
      different. CAT scan seems to be the best diagnostic imaging tool for the follow
      up of ARDS and barotrauma.

PMID- 1983489
TI  - [Perioperative chemotherapy of squamous cell cancer of the esophagus].
AB  - In the majority of patients with esophageal cancer local tumor infiltration
      and/or distant metastases are responsible for the poor prognosis. Therefore to
      improve life expectancy additional modalities--chemotherapy alone or in
      combination with simultaneous radiation--have been introduced perioperatively. In
      spite of a possible increase of resectability convincing data are lacking which
      could argue for an uncontrolled introduction of the neoadjuvant approach outside
      investigational studies in early tumor stages (T1, T2).

PMID- 1983490
TI  - [Fluid balance and postoperative lung function].
AB  - Postoperative volume therapy: 1. Replacement of fluid loss. 2. Therapy of
      intravasal hypovolaemia in case of permeability damage or intracellular fluid
      shift. Monitoring: 1. Circulation (HR, CVP, art. pressure). 2. Homeostasis (Na,
      K). 3. Metabolic changes (BE, pH). 4. Kidney function. In complications like
      sepsis or ARDS with pulmonary problems and increase of pulmonary vascular
      resistance the use of a pulmonary artery catheter is necessary. Differential
      treatment has to be based on additional measurement of cardiac output and
      pulmonary capillary pressure. Volume treatment in postoperative complications is
      essential because of intravasal hypovolaemia. Kidney and cardiac failure have to
      be ruled out.

PMID- 1983491
TI  - [Perioperative respiratory therapy and postoperative pain therapy].
AB  - Especially patients with preexisting bronchopulmonary diseases or those
      undergoing operations in the upper abdomen or thoracotomies are susceptible to
      post-operative pulmonary complications. All patients at risk should learn the
      prophylactic respiratory maneuvers preoperatively. Perioperative use of incentive
      spirometers, breathing exercises or IPPB seems to reduce the incidence of
      postoperative pulmonary complications. Opioids are used usually for postoperative
      pain management, but unfortunately they are given mainly as i.m. injections,
      although an i.v. administration would be far better. If given in an equipotent
      dose, nearly every opioid provides sufficient postoperative analgesia. Wide
      interindividual variation in the needed dose requires that opioids be titrated
      intravenously.

PMID- 1983493
TI  - [Postoperative lung complications: special problems exemplified by esophageal
      surgery].
AB  - Pulmonary problems in esophageal surgery can result from the resection itself
      (intraoperative pulmonary trauma), the reconstruction procedure (intrathoracic
      organ interposition) and aspiration due to postoperative impairment of
      swallowing. Therapeutic strategies include postoperative ventilation, deflation
      of the interponate and a special dietary plan. Our rate of 5.2% postoperative
      pulmonary complications underlines the efficiency of our treatment modalities.

PMID- 1983492
TI  - [Long-term intubation and tracheotomy].
AB  - Benefits and disadvantages of long-term nasal and oral endotracheal intubations
      vs. tracheotomy are discussed. The incidence and severity of complications is
      higher following prolonged endotracheal intubation than tracheotomy. Laryngeal
      injury is more serious than tracheal. Tracheotomy therefore is advantageous in
      all patients requiring long-term ventilatory support. The optimal timing for
      tracheotomy is ranging from 48 to 120 hours following endotracheal intubation.
      Tracheal stenosis secondary to trachestomy depends on tracheal wall perfusion.
      The risk of tracheal stenosis may be minimized by diligent performance of
      tracheostomy, and by sewing the trachea to the skin, and by using solidly fixed
      tracheal cannulas with high-volume low-pressure cuffs.

PMID- 1983494
TI  - [Acute respiratory distress syndrome of the adult: are there new therapeutic
      approaches?].
AB  - The mortality of adult respiratory distress syndrome (ARDS) remains high despite
      increasing understanding of the syndrome's pathophysiology, better monitoring and
      new ventilatory techniques. The outcome can be improved adequate systemic oxygen
      availability, improved infection control, and biochemical monitoring and
      interventions. Only by combinating of several treatment modalities is there a
      reasonable chance to change the prognosis of ARDS.

PMID- 1983495
TI  - [Extracorporeal membrane oxygenation and CO2 elimination].
AB  - The mortality in patients with ARDS stage IV is 90% according to the
      classification of Morel (1985) since all experiments as treatment with
      prostaglandine antagonists and application of antioxidants have to improve the
      outcome of such patients, we treated 87 patients, aged 5-51 years, between 1985
      1990, with a veno-venous extra-corporeal bypass for CO2-elimination and with low
      frequency positive pressure ventilation according to the method of Kolobow et al.
      Forty-six of 87 patients survived, i.e. the mortality was reduced to 47%. This is
      striking evidence that this method is superior to other treatments of patients
      with ARDS.

PMID- 1983496
TI  - [Perioperative problems in alcoholics and patients with cerebrovascular disorders
      -introductory references and questions].
AB  - 1. How can the diagnosis of "chronic alcohol abuse" be ascertained if the
      admission from the patient and his surroundings is lacking? 2. Is the operative
      risk for an alcoholic, aside from DT, reason for special prevention? 3. The
      practice of eliminating alcohol dependency by consuming drugs with similar
      effects: is polytoxicomania a reason for the increase in abortive delirious
      conditions? 4. Disagreement of pre- and perioperative prophylaxis for DT--yes or
      no? Questionnaire of 641 surgeons in 1/1990 in FRG: 30% no, 35% yes using
      alcohol, 35% yes with drugs. 5. Are drugs that are effective in DT also effective
      for prophylaxis? Combinations of four or more drugs can hardly be recommended if
      only because of the increased possibility of undesirable effects (interactions).
      6. There are two approaches in therapy of DT: substitution the alcohol by
      adequate substances and symptom-oriented differential therapy by combining 2-3
      pharmaceutic drugs.

PMID- 1983497
TI  - [Psychopathologic syndromes in alcoholic intoxication, drug abuse and cerebral
      ischemia].
AB  - The triadic system of psychiatry according to Kurt Schneider (1887-1967) is
      considered the systematic framework. The main forms of alcoholic poisoning,
      medication abuse and defective cerebral circulation are examined with regard to
      the unspecificity of psychopathological syndromes. Despite a considerable
      convergence there are quite a few differential diagnostic criteria, which are
      helpful in solving the perioperative problems of alcoholics and persons with
      medication dependency or defective cerebral circulation. All participants in the
      treatment of such patients must expand their knowledge of psychopathology and
      psychiatry.

PMID- 1983498
TI  - [Perioperative risk caused by alcohol and/or drug abuse. Which therapy?].
AB  - Alcohol and drug addicts usually suffer from polymorbidity. Withdrawal syndromes
      additionally endanger the success of surgical therapy. In opiate addicts
      withdrawal syndromes can and should be avoided by substitution of the drug or an
      analogon. In alcohol dependent patients the prophylaxis of withdrawal syndromes
      by i.v.-infusion of alcohol is not reliable. Therefore preference is given to the
      symptomatic therapy with combination of Benzodiazepin and Clonidin.

PMID- 1983499
TI  - [Alcohol withdrawal syndrome in the postoperative phase--therapy or prevention?].
AB  - In a prospective study 50 patients who reported regular ethanol consumption and
      who underwent neck dissection were evaluated by clinical examination and the
      Munich alcohol test (MALT). 31 patients were not classified as alcohol abusers
      and none of them developed withdrawal symptoms (WS) postoperatively. 19 patients
      were diagnosed as alcohol abusers; 9 of them (group 1) received symptomatic
      therapy with clomethiazol and haloperidol, 10 patients (group 2) received
      continuous ethanol infusions (2-4 g/h) postoperatively as prophylaxis for WS. 6
      patients in group 1 developed WS; none of group 2 developed WS. Thus the period
      of intensive care therapy of group 2 was significantly shorter (3.0 versus 11.5
      days). It was concluded that postoperative continuous ethanol infusions prevent
      the occurrence of WS and should be administered to severely alcoholic patients.

PMID- 1983500
TI  - [Treatment of postoperative alcohol withdrawal syndrome after esophageal
      resection].
AB  - Prophylaxis and treatment of alcohol withdrawal syndrome following esophagectomy
      consists of substitution with alcohol (1-2 g/kg/d), monotherapy with Midazolam
      (0.2-0.4 mg/kg/h) und Clonidin (1-2 mg/d). Out of 218 patients undergoing
      esophagectomy from X/86 till III/90 52 were classified as alcoholics and divided
      in 3 comparable groups. The Midazolamgroup showed the best results as far as
      withdrawal symptoms, time at the ICU, ventilation time, respiratory
      complications, delirium tremens and mortality are concerned. Patients in the
      Clonidin-group needed extensive supplimentary sedation.

PMID- 1983501
TI  - [Pathophysiology, clinical aspects and therapy of pre- and postoperative
      disorders of cerebral circulation and function].
AB  - The most important pathophysiological and pathogenetic facts are: The lower
      autoregulation threshold of cerebral blood flow and hypoxidosis, blood pressure
      in bradycardia, cerebral fits and stroke marks in CT, carotid atherosclerosis;
      reduced cerebral metabolism in chronic alcoholism and Wernicke. Reversible
      hypoglycemic induced hemiplegia. Multiinfarct syndrome and cerebral degenerative
      process Alzheimer. Effect of treatment by Piracetam.

PMID- 1983502
TI  - [Pharmacologic and clinical principles for rational anti-thrombotic preventive
      treatment with low molecular weight heparin].
AB  - Heparin exerts its anticoagulant function by accelerating the inhibitory effect
      of antithrombin III. Low molecular weight heparin (LMWH), which is derived from
      unfractionated heparin (UFH), exhibits marked anti-Xa activity and minor thrombin
      inhibition. It has an elevated bioavailability and longer half-life as to the
      anti-Xa clearance when compared to UFH. Platelet, endothelial and fibrinolytic
      effects are also involved in antithrombotic action. Clinical trials have shown
      that LMWH compared to UFH is an equivalent and even advantageous method of
      antithrombotic prophylaxis in surgical patients and has also a minor risk of
      bleeding.

PMID- 1983503
TI  - [Can the individual risk of the patient for thromboembolic complications be
      estimated? What references can be used for differential therapeutic procedure?].
AB  - In 1988 and 1989 4581 patients had been hospitalized in the surgical department
      of the Stadtkrankenhaus Neuwied. These patients were treated prophylactically
      with a combination of low molecular weight heparin and dihydroergotamine in order
      to prevent deep vein thrombosis. The observed incidence of DVT and pulmonary
      embolism was extremely low. In patients who died during hospitalization, death
      was mainly caused by cancer or multimorbidity. Although some risk factors for
      developing DVT are recognized, we are at present not able to calculate the
      individual risk of a patient. Therefore, we need an effective and safe
      prophylaxis regimen for all patients undergoing surgical operations.

PMID- 1983504
TI  - [Prevention of thrombosis with low molecular weight heparin as the only substance
      and/or with DHE: results of clinical studies].
AB  - In aspect of the high incidence of thrombosis and the resulting risk of fulminant
      pulmonary embolism and late complications, there is a demand for a general
      medical prophylaxis in operative medicine. A new chance to reduce the incidence
      of thrombosis is the recently developed low weight molecular heparine (LWMH).
      Current studies of different LWMH in general and thoracic surgery prove, that an
      effective decrease of thrombosis can be achieved with a single daily injection.
      Effectiveness of LWMH in high risk patients have not been sufficient evaluated
      yet in some of the used preparations.

PMID- 1983505
TI  - [Low molecular weight heparin in vascular surgery patients].
AB  - In contrast to general surgery postop. thromboprophylaxis in vascular surgery
      cannot be standardized because the risk of thrombosis differs considerably among
      different types of operations. Following peripheral reconstructions prophylaxis
      of arterial thrombosis will cover all aspects of venous thromboprophylaxis too.
      Only in operations without any arterial prophylaxis subcutaneous heparin for
      venous thromboprophylaxis is essential. The therapeutic value of low molecular
      heparin fraction has not yet been clarified so far.

PMID- 1983506
TI  - [Surgical treatment of stomach cancer].
AB  - Adequate surgical radicality in regard to the extent of gastric resection as well
      as to systematic lymphadenectomy with the aim of R-0-resection is the treatment
      of choice in gastric carcinoma. The demand for such a procedure based on the
      results obtained in the last years with increasing rates of resectability
      together with decreasing operative mortality. In the own material among a total
      of 1704 operations for gastric carcinoma the rate of resectability raised from
      70% to 81.5% whereas overall operative mortality fell from 17.5% to 4.7%. The 5
      year survival rate following different resective procedures was 26%; if these
      results can be improved by perioperative chemotherapy must be verified by running
      multimodality treatment studies.

PMID- 1983507
TI  - [How is the use of low molecular weight heparin in regional anesthesia
      evaluated?].
AB  - It is difficult to predict the risk of bleeding in regional techniques under
      concomitant LMH administration, as each LMH preparation has a particular mode of
      action and different pharmacological properties. Although complications due to
      bleeding, that occurs during the execution of a regional technique, are extremely
      rare, epidural anaesthesia with or without a catheter should be avoided during
      LMH administration. Where strongly indicated, a spinal anaesthetic can be
      performed by an experienced colleague. Epidural anaesthesia should not be carried
      out until at least 12 hours after the last dose of LMH.

PMID- 1983508
TI  - [Prevention of thrombosis in surgery: low molecular weight heparin/standard
      heparin].
AB  - In a randomized study the efficiency of the low molecular weight heparin (LMWH)
      Fragmin and unfractionated heparin Calciparin in preventing thromboembolic
      disease was examined. Ninety patients undergoing a herniotomy participated in the
      study. The LMWH also showed good efficiency in a laboratory test of anti-factor
      Xa-activity. There were no complications.

PMID- 1983510
TI  - [Gallstone therapy--cooperation or competition?].
AB  - The gold standard in the therapy of the gallstone disease ist cholecystectomy,
      which today is performed by way of a minilap-cholecystectomy. Therapies in
      competition with the operative treatment are: oral chemolitholysis, shock wave
      lithotripsy and the direct, intraluminal methods of lithotripsy. For each
      procedure there is a special range of indications; therefore treatment of
      gallbladder stones should be decided on individually, as each therapeutic
      procedure has its advantages and disadvantages.

PMID- 1983509
TI  - [Perioperative prevention of thromboembolism with low molecular weight heparin
      and postoperative bleeding complications].
AB  - In three studies the effect and secondary effect of low molecular weight heparin
      (LMWH) were examined. Study 1: LMWH (Embolex-LM, n = 464) versus standard heparin
      (Liquemin, n = 452); Study 2: LMWH (Sandoparin, n = 298) versus standard heparin
      (n = 296). In the 3rd study controls of LMWH were performed in the clinic of
      visceral surgery, and the clinic of traumatology both. During these three studies
      all excluded patients who did not receive a thromboembolic prophylaxis were also
      examined. The first two studies showed no significant differences in the
      frequency of thromboembolic and bleeding complications. The bleeding complication
      was the same (3-6%) in the group of excluded patients. This is valid for study 3
      too. In all studies the surgeon had an important influence on the frequency of
      bleeding complications.

PMID- 1983511
TI  - [When should gallstones be treated?].

PMID- 1983512
TI  - [Cholecystectomy--the gold standard of therapy].
AB  - Elective CCE is still the treatment of choice for more than 80% of patients with
      gallstone disease. Surgery is indicated for biliary symptoms along with
      sonographic or radiographic evidence of gallstones and/or pathology of the
      gallbladder wall. Non-operative procedures are limited to patients with open
      cystic duct, preserved contractivity of the gallbladder and non-calcified stones.
      Mortality of elective cholecystectomy in patients less than 70 years today is 0.
      Emergency cholecystectomy and old age (greater than 70) are the only mortality
      risk factors amounting up to 4%. Recurrent surgery is necessary in less than 1%
      of the patients, conservatively treated postoperative morbidity less than 5%.
      Cholecystectomy still remains the only method, by which immediate stone release
      is achieved and long term medication avoided.

PMID- 1983513
TI  - [Therapy of acute cholecystitis--importance of early operation].
AB  - The acute cholecystitis is caused in over 95% by an stone occlusion of the cystic
      duct. The diagnosis can be made securily by ultrasound. The early
      cholecystectomy, th.i. within 48 hours, is the management of choice. The urgent
      cholecystectomy is indicated in free perforation of gallbladder or empyema with
      septicaemia. The late cholecystectomy should be refused avoiding unsuspected
      further complications. The mortality of 551 patients, operated in 16 years, has
      been totaly 27 (= 4.9), only 7 Patients (= 1.3%) immediately as an consequence of
      the gallbladder operation.

PMID- 1983514
TI  - [Postcholecystectomy syndrome--still a current argument today?].
AB  - The "postcholecystectomy syndrome" was originally defined by Pribram as a pure
      functional disturbance after cholecystectomy. Today it has become a melting pot
      of various postoperative syndromes of mostly obscure origin. It's incidence is
      said to be 26-40%, but surgically treatable lesions of the biliary system amount
      only 1.5%. Functional consequences for biliary excretion are rare because the
      loss of the gallbladder reservoir is substituted in part by the biliary tree.

PMID- 1983515
TI  - [Oral litholytic therapy--a reliable therapeutic principle?].
AB  - Oral litholysis by bile acids be used for the treatment of non-calcified
      cholesterol gallstones but not for the treatment of pigment stones. A
      prerequisite is that the patient has no complicated gallstone disease, has
      relatively little symptoms and has a functioning gallbladder. Gallstones with a
      diameter of more than 1.0 cm, before oral bile acid treatment, should undergo
      fragmentation by lithotripsy.

PMID- 1983516
TI  - [Shockwave lithotripsy in gallbladder and bile duct calculi: indications and
      results].
AB  - Extracorporeal shock-wave lithotripsy combined with adjuvant litholytic therapy
      (ursodeoxycholic acid and chenodeoxycholic acid) is a relatively safe and
      effective noninvasive therapy for selected patients with symptomatic radiolucent
      gallbladder stones. The best results (80% stone-free patients within 1 year) are
      obtained with radiolucent solitary stones with a diameter of less than 20 mm.
      Shock-wave lithotripsy achieves rapid clearance of stones in about 80% of
      patients with bile duct calculi in whom endoscopic procedures fail.

PMID- 1983517
TI  - [Percutaneous transhepatic litholysis--indications, results, risks].
AB  - A total of 170 patients with symptomatic cholesterol stones in the gallbladder
      were scheduled for percutaneous transhepatic dissolution with MTBE. Puncture was
      successful in 167/170 patients; stones dissolved in 161/167. The treatment of
      solitary stones averaged 3.9 hours, whereas multiple stones required 9.6 hours.
      The mean hospitalisation time was 3.6 days. After litholysis 1/3 of the patients
      had sludge in the gallbladder; most of them were free of residue after treatment
      for 3 months with UDC/CDC. Complications included hemobilia in 2/167, perforation
      in 1/167 and bile leakage in 7/167 (5 had surgery).

PMID- 1983518
TI  - [Surgical bile duct revision--indications, technique, results].
AB  - Nonsurgical methods compete with common bile duct exploration (CBDE) in the
      treatment of choledocholithiasis. Following CBDE residual duct stones are found
      in 6% of cases and the mortality is 2%. In our patients (n = 373) the numbers
      were 5.4% and 1.6% respectively. The lowest rates of residual duct stones were
      seen following a combination of intraoperative cholangiography and
      choledochoscopy. CBDE is indicated when cholecholithiasis is discovered
      intraoperatively, in low-risk patients with gallbladder and bile duct stones,
      after unsuccessful endoscopic procedures, in cases, of other pathologic findings
      of the bile duct requiring surgery or even in younger patients after prior
      cholecystectomy.

PMID- 1983519
TI  - [Therapeutic decision in gallstone disease from the internal medicine viewpoint].
AB  - Bile duct stones can be treated by conventional operative endoscopy in up to 90%.
      Stones with a diameter of up to 10 mm may be treated without endoscopic
      sphincterotomy (EST), larger stones require EST and subsequent mechanical
      lithotripsy. Extracorporeally generated shock-wave lithotripsy (ESWL) is
      indicated in huge (phi greater than 15 mm), hard, and intrahepatic calculi. High
      risk patients are palliatively treated with transpapillary stent. Symptomatic
      gallbladder stones require surgical therapy in up to 85%. Only selected patients
      are candidates for oral litholytic therapy (phi less than 10 mm) or ESWL (1-3
      radiolucent stones, phi 10-30 mm). Percutaneous transhepatic litholysis is not
      yet established as therapeutic alternative.

PMID- 1983520
TI  - [Therapeutic decision in gallstone disease: from the surgical viewpoint].
AB  - Cholecystectomy, hitherto the "golden standard" in gallstone treatment, and all
      the other alternative methods must pass the test of applicability, morbidity,
      mortality, rate of success and recurrence. According to these criteria,
      cholecystectomy (removing not only the stones but also the offending gallbladder)
      -in particular with the advent of the laparoscopic approach--is the therapy of
      choice.

PMID- 1983522
TI  - [Cooperation between experimental and clinical surgery--from the experimental
      viewpoint].
AB  - Experimental surgery in german various forms of organisation and different aims
      as regards cooperation between experimental and clinical surgery. The best and
      most effective form is that of an institute with good personnel, adequate
      finances and sufficient space. An essential prerequisite for good cooperation
      between experimental and clinical surgeons is that the scientific aims be
      initiated by both. Success is possible only, if continuity can be guaranteed over
      a longer period. This is possible only in well established institutes of
      experimental surgery.

PMID- 1983521
TI  - [Models for cooperation between experimental and clinical surgery--from the
      clinical viewpoint].
AB  - In order to cope with the tasks in the field of surgical research manifold models
      of cooperation have developed in Germany: 1. the independent Institute for
      Experimental Surgery, 2. the partly independent Section for Experimental Surgery,
      3. the unindependent Section for Research, 4. the Clinical Research Group and 5.
      the Interdisciplinary Research Group. The efficiency of this cooperation between
      researchers and clinicians is dependent on the availability of research
      laboratories, the inclusion of methodological specialists, an adequate keeping of
      laboratory animals, independent funds for research, and on a certain amount of
      free time which can be dedicated to research activities, devoid of clinical
      obligations; a high methodological standard and a good knowledge of the clinical
      and scientific fields are fundamental.

PMID- 1983523
TI  - [The importance of animal research for experimental surgery].
AB  - Animal experiments in biomedical research are ethically indispensable to minimize
      risks and to objectify superiority of diagnostic and therapeutic procedures.
      Innovative models allow understanding of complex systems and to formulate new
      hypotheses, however due to inherent limits cannot replace animal research. The
      high degree of complexity required for surgical experiments can often be achieved
      in small animals and allows to save domestic animals. Further expansion of
      biomedical research will not be associated with a greater number of animal
      studies.

PMID- 1983524
TI  - [What is the role of ethics commissions for clinical research?].
AB  - Professional and drug development laws require that each project involving human
      research is submitted to a specially appointed independent committee (Ethics
      Committee) to ensure conformity with the ethical principles of the medical
      profession (Declaration of Helsinki). Today the public demands this prerequisite
      for clinical research. The main goal is to protect the patient or proband from
      unjustified risks. The interest of the subject must always prevail over the
      interests of science and society.

PMID- 1983525
TI  - [Efforts toward harmony within the scope of the European Community. What has been
      accomplished, what remains to be done?].
AB  - Report about harmonization of surgical training in the E.C. countries.
      Responsibility of the U.E.M.S. (European Union of Medical Specialists), in
      particular of the section of surgery. Each country is represented by two members.
      Annual meetings. A harmonization committee has been founded under direction of
      Prof. Gruwez, Leuwen/Belgium. A first report on the harmonization of surgical
      training in the E.C. countries is available. Standards of quality shall be
      reached. Consideration to found a European Board of Surgery.

PMID- 1983526
TI  - [Teaching and learning--the surgical craft].
AB  - Changes in surgical clientele made it necessary to reassess the operative
      training for surgeons. The aim must be to make surgical procedures and techniques
      transparent enough for learning and teaching. Today, it is possible to practice
      and to learn the reconstructive part of an operation, that means the suture
      techniques, independently of the patient. The difficulties in anastomotic
      techniques can be simulated, too. But it is still difficult to practice the
      preparatory part of an operation without patients, in other words: cold. By
      creating adequate models this problem will be solved in the near future.

PMID- 1983527
TI  - [Becoming a surgeon from the perspective of orthopedics courses].

PMID- 1983529
TI  - [Becoming a surgeon--at the large community hospital].
AB  - There is no correlation between the number of places for surgical education and
      the real demand for surgeons. In Bavaria 86.7% of all surgeons licensed to train
      surgeons between 1-6 ys. took part in an inquiry. They asked for 25-30% surgeons
      in their residency staff but got only 8-24% in reality. In addition 60.2% of all
      resident wait for a place to finish their surgical training in fully licensed
      hospitals. In a big community hospital there are no problems for residents to get
      the needed number of operations. Beside this surgical education should include 6
      months clinical training in ICU, 2.5 ys. general, 1.5 trauma and 1 year vascular
      thoracis surgery. Basic science and research can be done only in universities,
      but clinical control of patients outcome, i.e. in tumor patients is mandatory.

PMID- 1983528
TI  - [Becoming a surgeon--at the university clinic].
AB  - The "surgeon's road" in an university department is marked by the demands of
      research, clinical work and teaching. The demands made by all 3 can hardly be met
      in the prescribed 6 years of training when adhering to the statutory 38.5 hours
      week. At present there are 1227 surgeons "on the road" at West German surgical
      departments (12% are women). Of these some 24% will reach a consultant post and
      less than 2% will become chairmen of a university department.

PMID- 1983530
TI  - [Making a surgical decision: interplay between experience and clinical study].
AB  - Although the final, individual decision making in patients always has to be in
      the hand of the doctor, it has hitherto been much less a matter of scientific
      analysis than formal decision making on the basis of clinical trials. To change
      this, several types of individual decision making were characterized, four in the
      field of intuition (very fast logical decisions, consciously and unconsciously
      heuristic decisions using special instruments, the deep remainder of intuition
      which can and should not be the subject of scientific analysis) and discursive
      (purely logical) decision making as a fifth type. The prospective think-aloud
      technique including an hierarchical heuristic decision tree was presented as a
      method for scientific analysis of individual decision making which is open to
      repetition and criticism. The place of various types of formal trials in this
      process was defined. Via a posit and the heuristic instrument of
      representativeness, the problem of the transfer of results from clinical trials
      to the individual patient was solved.

PMID- 1983531
TI  - [Effect and importance of experience in determining indications and surgical
      technique].
AB  - Medicine is an empirical science in which there are very heterogeneous view about
      the importance of experience. Numerical data attempt to quantify the required
      experience for student education and clinical practice. Support systems, i.e.
      scores, decision trees, etc., facilitate decision-making for surgical indications
      and choice of operative techniques. They are aided by clinimetrical systems, i.e.
      controlled clinical trials and even computer assistance. Beyond all strategies of
      decision-making lies the accumulated individual experience of making the right
      decision at the right time. Experience is also at the bottom of the often cited
      intuition, clinical judgement and common sense.

PMID- 1983532
TI  - [Effects of intuition on determining indications and intraoperative procedure].
AB  - Intuition is used in medical decision-making, especially in a decision for
      surgery and in selection of the surgical procedure. Intuitive decisions are made
      without reasoning. They are often correct if the prerequisite experience and
      knowledge are available to the physician. Intuition is related to heuristic
      techniques and uses them (representativeness, availability, anchoring). Decisions
      made on the basis of intuition must be controlled by systematic and logical
      reasoning.

PMID- 1983533
TI  - [Effect of errors (particularly one's own!) on making surgical decisions].
AB  - Looking for medical errors in clinical practice we reviewed several cases from
      our daily indication and case conference, 6 cases discussed in the lethality
      conference and 9 which were treated by legal institutions. The points of
      criticism were analysed. We discriminated between diagnostic, therapeutic
      failures and those of organisation. The basis were 4045 patients with 4583
      operations during the year 1989. The overall lethality was 1.2%. The instruments
      of avoiding medical errors in individual and general sense were shown.

PMID- 1983534
TI  - [Mixing results of prospective and retrospective studies by objective decision
      analysis: evaluating probability by healthy human minds?].
AB  - The major shortcomings of formal decision analysis derive from the complexity of
      the clinical problem, behavioral qualities of the investigator and the method
      itself. It seems difficult to translate study results into a probability estimate
      for the problem in an individual patient. Therefore, probability assessments from
      the medical literature, one's own clinical experience and data sources should be
      combined. Decision analysis is not itself clinical reality but provides a model
      for thinking explicitly about the problem.

PMID- 1983535
TI  - [Interdisciplinary computerized evaluation of perioperative risk factors].
AB  - The identification and assessment of perioperative risk factors combined with
      interdisciplinary management may lead to minimized risk for the patient. The
      numerous medical and administrative data should be collected by a computer. This
      was done in a preliminary study at the university of Bonn, where 9772
      anaesthesias given for general surgery were evaluated. The necessary outcome
      studies should be based on statistical evaluation of the data (factor analysis)
      and their interpretation should be an interdisciplinary concern.

PMID- 1983536
TI  - [Individual prognosis in gastroduodenal ulcer hemorrhage: practical application].
AB  - Using modern methods of medical decision making (regression analysis) one can
      determine risk factors for rebleeding in peptic ulcer disease. Prediction of
      rebleeding for the individual patient is possible. Under regard of five effective
      risk factors and using adequate statistical methods, sensitivity and specificity
      reach about 80%.

PMID- 1983537
TI  - [Is advanced age by itself a risk factor in large abdominal surgical
      interventions].
AB  - A logistic regression analysis was performed retrospectively in 237 patients over
      70 years of age (group 1) who underwent surgery for diseases of the biliary
      tract, stomach, and colon and rectum. The data were compared with those of 273
      patients with identical operations under the age of 60 years (group 2). The
      results of our analysis differed according to the cohort of patients. Age was
      shown to be a significant risk factor for perioperative mortality according to
      the analysis of young and old patients (group 1 and 2). Analysis of group 1
      showed that the urgency of the operation and the sum of coexisting morbidities
      were significant. The combination of age and urgency is a significant risk factor
      following colorectal but not gastric and biliary surgery.

PMID- 1983538
TI  - [Surgical thoracoscopy].
AB  - Thoracoscopic adhesiolysis since 1913 (Jacobaeus). Thoracoscopic targets:
      Sympathetic system, vagus system, lymphatic system, lung. INDICATIONS: Arterial
      circulation disturbances, posttraumatic reflexdystrophy ("Sudeck"), Hyperhidrosis
      syndromes, erythrodermy syndromes; pain syndromes: causalgiform, splanchnicotomy
      for chronic pancreatitis. For peptic jejunal ulcer thoracoscopic splanchnico
      vagotomy. For bronchial asthma selective vagotomy of bronchial rami. Operative
      techniques. Hemostasis: low-frequency thermocoagulation, unipolar and bipolar
      high-frequency coagulation, with thermostabilisation. Videoendoscopy with
      minicameras. Electronic frame freezing for colour slides.

PMID- 1983539
TI  - [Percutaneous endoscopic tracheostomy].
AB  - Between 6/88 and 8/89 61 critically ill patients (sepsis, ARDS, pneumonia,
      multiple trauma, etc.) underwent elective percutaneous endoscopic tracheostomy
      (PET). Following dilation up to 36 Fr. a number 6-10 tracheostomy tube was
      introduced. The patients were ventilated 17 (2-68 days) before and 28 (4-160)
      days after PET. One patient died from cardiac arrest, and in 4 patients, because
      of tube obstruction or cuff defect, reintubation was necessary. Additionally 2
      significant infections and a minor bleeding and a emphysema occurred. Elective
      percutaneous tracheostomy performed in the ICU seems to be a simple and cost
      effective procedure.

PMID- 1983541
TI  - [Laparoscopic appendectomy--alternative therapy in all stages of appendicitis?].
AB  - 1989 we reported on our first series of 277 laparoscopic appendectomies. This
      technique was introduced by Semm in 1982. We acquired this procedure in 1987 and
      modified this operation-technique for surgical routine. We could demonstrate that
      laparoscopic appendectomy can be performed in chronic, acute and even in peracute
      cases. We introduce the facts of 500 laparoscopic appendectomies.

PMID- 1983540
TI  - [Laparoscopic surgery of gallstones--report of treatment of 157 patients].
AB  - From November 1988 to February 1990 157 patients with gallbladder stones haven
      been treated by a laparoscopic surgical procedure. They are 28 males and 129
      females from 13 to 81 years old. 18 have had a cholecystostomy after
      intracorporeal lithotripsy (Lus Ultrasonic Olympus). They were placed on bue
      acids during 3 months. The average follow up time is 11 months. The mortality is
      zero and 2 mild complications occurred medically cured. 3 patients have a
      recurrent stone 6 months after surgery. 139 patients have had a cholecystectomy
      89 after the same lithotripsy procedure seen above, 50 without prior lithotripsy.
      In 3 cases the laparoscopic procedure was abandoned, twice because of a sever
      bleeding, one for too compact surrounding adhesions. The mean follow up is 9
      months. 123 were drained 1 day 16 had no drain. The mortality is zero. 2 patients
      without drainage developed a sub hepatic and douglas pouch abscess. They were
      cured by a lavage drainage laparoscopically made. 1 patient with drainages had a
      7 days bile leak, which disappeared spontaneously. The 136 others have had a
      short stay in the hospital (2-4 days) a painless post operative time. They could
      go back to work and sport within 1 week. They have minimal scars and no danger of
      incisional herriae. The magnification of the optical system enables the
      dissection of the cystic duct and artery easier and safer than it is by mini
      laparotomy mostly in obese people. At the beginning of our experience only the
      patients with frequent biliary colics have been selected for the laparoscopic
      procedure. At that time 13 patients with subacute cholecystitis and 9 patients
      with stones in the commun bile duct have had a laparoscopic cholecystectomy
      associated with an endoscopic sphincterotomy in the last cases without
      complications.

PMID- 1983542
TI  - [Minimally invasive surgery in tumors of the esophagus].
AB  - The endoscopic-microsurgical dissection of the esophagus (EMDE) was developed to
      reduce the operative risk of resecting tumor-bearing esophagus. Utilizing an
      operation-mediastinoscope, the esophagus is freed from surrounding tissues in a
      circular fashion. Blood vessels are coagulated and cut. Under good endoscopic
      view and minimal blood loss, the esophagus can be freed via a cervical incision
      and extracted caudally. Up to now the EMDE has been utilized in 7 patients. The
      intra- and postoperative course was without problems. In the future, we further
      expect to see a reduction in cardio-pulmonary postoperative complications.

PMID- 1983543
TI  - [Laparoscopic cholecystectomy--initial experiences and results].
AB  - In a prospective pilot study on 100 consecutive patients with symptomatic
      cholelithiasis the laparoscopic cholecystectomy shows to be a safe technic
      without mortality and a low complication rate (3%). The time of operation is
      influenced by a learning curve of the operation-team and depends on the technical
      equipment. The postoperative hospital stay is 3 days in median. Postoperatively
      the pain-intensity is low and decreased very fast. These increased the patients
      perioperative comfort.

PMID- 1983544
TI  - [Power and responsibility in medicine].

PMID- 1983545
TI  - [Intraoperative radiotherapy of pancreas and stomach cancer].
AB  - IORT can be part of an oncologic treatment plan for patients with pancreatic or
      advanced stomach cancers that can be potentially cured by surgery. When used
      palliatively IORT can relieve symptoms. Used curatively IORT allows the
      administration of irradiation boost which complements percutaneous irradiation of
      the tumor region and the regional lymph nodes. External radiotherapy may also
      include irradiation of the liver which is performed simultaneously with
      chemotherapy. IORT also permits the application of oncolytic doses for
      adenocarcinomas of the upper gastrointestinal tract.

PMID- 1983546
TI  - [Partial resection of primary liver cell cancer].
AB  - Between 1985 and 1990, 47 patients with primary hepatocellular carcinoma (HCC)
      underwent surgery (n = 27), chemoembolization (n = 12) or palliative resection
      followed by chemoembolization (n = 5). In 85% of the patients a T3/T4 tumor stage
      was found, 68% had liver cirrhosis and 42% were older than 70. Mortality was
      18.7% after liver resection and 0% after chemoembolization or combined treatment.
      Average survival was 4.4 months after chemoembolization, 11.6 months after
      resection and 11.6 months after palliative resection of the HCC followed by
      chemoembolization with angiostat/adriblastin.

PMID- 1983547
TI  - [Transplantation in primary liver cancer].
AB  - 33 patients with liver malignancy underwent transplantations. The overall
      survival rate 1, 2 and 5 years after transplantation was 42.4%, 30% and 24.2%,
      respectively. These figures agree with those of other centres. 16 patients with
      primary hepatocellular carcinoma had a median survival of 2 years and 2 months
      and a 5-year-survival rate of 37.5%, the longest followup being more than 11
      years. 10 patients with cholangiocellular carcinoma had a 5-year-survival rate of
      only 10%, the longest followup being more than 6 years. Patients with liver
      sarcoma and liver metastasis had a low survival rate and high tumor recurrence.
      Transplantation is generally well accepted for primary hepatocellular carcinoma.
      For other malignancies it should be considered an exception, provided that
      extrahepatic tumor spread has been ruled out.

PMID- 1983549
TI  - [Adjuvant radiotherapy of rectal cancer].
AB  - Evaluation and refinement of surgical techniques in rectal carcinoma have reduced
      the rate of local recurrences. Nevertheless recurrence it remains high at more
      than 20% in patients with extensive infiltration of perirectal tissues and cures
      are an exception. Overview of many years of experience with adjuvant radiotherapy
      shows that local recurrence rate can be reduced and survival the rate improved.

PMID- 1983548
TI  - [Surgery of colon and rectal cancer].
AB  - Surgery of colorectal cancer is also surgery of lymph node compartments and
      tissue planes. It is essential in such surgery to avoid tumor dissemination and
      inoculation while observing safety margins. If surgical procedures are strictly
      standardized according to the rules of surgical oncology R0-resection will yield
      extraordinarily favourable results not only for stage I but also for stages II
      and III tumors. There are distinct differences between colon and rectal carcinoma
      in stage II disease, indicating a different biologic behaviour of these tumors.
      The possibility of further improvement of the good results of R0-resection by
      adjuvant therapy should be addressed in future studies.

PMID- 1983550
TI  - [Is there a reliable adjuvant (intraoperative) chemotherapy of colorectal
      cancer?].
AB  - On the basis of a considerable number of carefully designed, representative, and
      controlled studies adjuvant chemotherapy was considered uneffective for patients
      with colorectal cancer. In the light of the very recently published results
      obtained with the combination of 5-fluorouracil plus levamisole this option must
      now be reconsidered. However, the statement of the NCI that all patients with
      Dukes'C cancer should be offered this combination appears premature.

PMID- 1983551
TI  - [Laser and afterloading therapy of bronchial cancer].
AB  - Endobronchial afterloading irradiation by remote control was administered to 304
      patients with lung cancer. The use of a highly active 192-Iridium source (740
      GBq) is possible; irradiation time lasts only a few minutes. A combined treatment
      modality with laser was employed in 24%, with chemotherapy in 2%. The response
      rate of all patients amounted to 67%. There was an improvement in 81% of patients
      with retrostenotic complications.

PMID- 1983552
TI  - [What is the value of tumor debulking and intraperitoneal cytostasis].
AB  - Local recurrences of intraperitoneal malignancies are mainly localized at the
      primary tumor site and the peritoneal surface. Surgical procedures alone are
      neither able to further reduce the development of local recurrence nor to treat
      the already established recurrent disease. In this situation intraperitoneal
      chemotherapy as an "adjuvant" treatment modality could be thought helpful.
      Experimental and clinical trials have shown that high doses of cytotoxic agents
      can be applied to the abdominal cavity with less systemic side effects. While the
      recent published data are not promising for gastrointestinal malignancies, they
      seem to be more encouraging for ovarian cancer.

PMID- 1983553
TI  - [Chemoembolization of primary liver cancer].
AB  - At the University of Frankfurt/M. we perform chemoembolization of the liver in
      patients with inoperable liver cell carcinoma. Before application of embolization
      material vasoconstriction of healthy blood vessels is achieved by intraarterial
      injection of norepinephrine. This procedure improves selectivity of tumor
      embolization. Methods, indications, contraindications and results are presented.

PMID- 1983554
TI  - [Surgical interventions in liver metastases].
AB  - Surgical treatment of hepatic metastases is predominantly aimed at "curative"
      resection. This can be achieved in about 20% of colorectal secondaries, and is
      associated with a 30-40% 5-year survival. One to three metastases in the absence
      of extrahepatic disease are regarded a clear indication to resection. Among
      patients with non-colorectal malignancies, occasional long term survival was
      reported in leiomyosarcoma, breast cancer, and renal cancer metastases,
      respectively. Endocrine tumors such as carcinoid, gastrinoma, or
      pheochromocytoma, are different because of their remarkable symptoms along with a
      protracted natural history. Quality of life may be considerably improved here by
      even non-radical debulking. The vast majority of patients, however, ist not
      suitable to undergo hepatic resection. Palliative therapeutic options involve
      hepatic artery ligation or embolization, cryo-surgery and percutaneous laser
      coagulation, and various types of regional chemotherapy. These methods may enable
      a temporary relief of symptoms, but no significant impact on survival time, and
      no true long term benefit has been proven. Prospective randomized trials against
      combined treatment as well as untreated patients are required for a more
      meaningful judgement and improved effectiveness.

PMID- 1983555
TI  - [Combined regional chemotherapy and radiotherapy of liver metastases].
AB  - In an attempt to treat patients with non-resectable liver metastases more
      effectively, hepatic arterial chemotherapy (12 g 5-FU in 3 weeks) was combined
      with simultaneous whole liver irradiation (8 Gy every week, total dose of 24 Gy).
      54 of the 64 patients receiving this treatment had liver metastases from
      colorectal carcinoma. The objective response rate, judged by CAT scan, was nearly
      60%. The median survival of responders was 18 months in contrast to 8 months for
      nonresponders. There have been 5 lethal complications, 3 of which were related to
      the combined modality. For safer and better results a more exact selection is
      needed.

PMID- 1983556
TI  - [Differential after care for early detection of recurrence: from the surgical
      viewpoint].
AB  - Tumor recurrence following "curative" resection (= R0) of gastrointestinal cancer
      occurs in 30% (colorectal carcinoma) to 70% (ductal pancreatic cancer) of
      patients. Only colorectal cancer recurrence involves a substantial chance of a
      reintervention which again may result in complete cancer clearance (local
      recurrence 17%, metachronous liver metastases 20%, other abdominal intracavitary
      relapse 12%, pulmonary secondaries 17%). Five-year survival after complete re
      resection approaches 40% irrespectively of the site of recurrent disease.
      Recognition of resectable recurrence in asymptomatic patients is based on
      ultrasound, endoscopy, and chest X-ray. Laboratory investigations alone, and even
      CEA-screening, do not suffice.

PMID- 1983557
TI  - [Differential after care for early detection of recurrence from the radiologic
      viewpoint].
AB  - Diagnostic imaging plays only a minor role in the followup of local recurrencies
      in tumor patients. Patient history, clinical and biochemical findings as well as
      endoscopy are more important. The diagnosis of lymph node and other metastasis,
      however, requires imaging procedures. Although metastasis can be diagnosed
      earlier nowadays, they must still have a macroscopic size to be detected.
      Accuracy of the diagnostic procedures depends on the chosen "golden standard".
      The higher the standard, the more unreliable are imaging procedures which
      depending on tumor type and site of metastasis are reduced to accuracy rates of
      below 50%.

PMID- 1983558
TI  - [Differential after care for early detection of recurrence--from the general
      practice viewpoint].
AB  - A field-research on follow-up of GI-Carcinoma in 1989 with contributions of 159
      general practitioners and physicians of Hamburg city area revealed some specific
      problems in performance and quality: lack of communications by and insufficient
      and inconstant qualifications of involved hospital staff as well as high rate of
      deficits in knowledge of necessary systematic examinations in symptom free
      patients.

PMID- 1983559
TI  - [After care in treatment of functional disorders after tumor excision--from the
      surgical viewpoint].
AB  - Radical cancer surgery cures by setting defects. Consequently there are limits to
      the conservation or restoration of organ functions. These problems are mainly
      relevant to gastric and rectal surgery. Conservative treatment is the treatment
      of choice for functional deficiencies. If it fails, surgical intervention can be
      successful in rebuilding reservoir functions and eliminating transport
      disturbances, but it can only poorly imitate the function of digestive
      sphincters.

PMID- 1983560
TI  - [Physiology and pathophysiology of intestinal circulation].
AB  - Splanchnic blood flow is regulated by cardiovascular factors, the autonomic
      nervous system, circulating vasoactive agents and local mechanical factors.
      Typical physiologic phenomena such as "autoregulation", "autoregulatory escape"
      and "countercurrent exchange" are discussed. Aspects of therapy especially for
      acute mesenteric infarction, are elucidated with reference to the circulating
      vasoactive agents, the effects of bowel distension on intestinal blood flow and
      reperfusion injuries.

PMID- 1983561
TI  - [Acute mesenteric vascular occlusion: pathophysiology, clinical stages,
      diagnosis].
AB  - Advanced age and cardiovascular diseases cause of SMA occlusion. Shock is
      triggered and maintained by bowel ischemia. Since lactate is the end product of
      anaerobic glycolysis, lactacidosis is a valuable clinical parameter. Lactate
      values above 4-5 mmol/l are conclusive evidence in the presence of symptoms of
      acute SMA occlusion. Chance of survival are poor in stages II and III with
      advanced shock and non reversible gangrene. Revascularisation of the SMA combined
      with adequate bowel resection reduces the production of toxic and lethal
      substances in the intestinal mucosa, thus increasing the chance of survival.
      Determination of serum lactate should be an integral part of the diagnostic
      procedure and the close followup for it is both an adequate index of the grade of
      intestinal ischemia and a means of assessing whether a second-look is warranted.

PMID- 1983562
TI  - [Non-occlusive disease--ultrasound diagnosis and trend analysis as a treatment
      guideline].
AB  - 16 patients with angiographically proved NOD underwent immediate abdominal
      sonography (age: 76 +/- 24 years). All patients suffered from "low cardiac output
      syndrome". The sonographic criteria were as follows: bowel wall edema [16], hyper
      peristalsis [16], free peritoneal fluid [14], and signs of incomplete ileus [14].
      11 patients were successfully treated with conservative therapy on the basis of
      followup ultrasound observation and analysis. 5 patients underwent operation
      because of worsening ultrasound findings. These patients died from the underlying
      cardiac illness.

PMID- 1983563
TI  - [Surgical therapy of acute mesenteric artery occlusion].
AB  - Only early diagnosis and vascular surgery during the period of ischemic tolerance
      (about 12 hours) will improve the results of treatment of acute splanchnic artery
      occlusion. From 1966 to 1989, 98 patients were treated: 81 underwent operations
      (65 emboli of the SMA, 16 arteriosclerotic obstructions). Of the 47 patients who
      were treated at the stage of reversible acute mesenteric ischaemia 12 died
      (25.5%). Of the 34 patients undergoing surgery at the stage of small bowel
      infarction 24 died postoperatively (70.6%).

PMID- 1983564
TI  - [Indications and results of second-look operation in acute mesenteric vascular
      occlusion].
AB  - In acute mesenteric infarction (AMI) assessment of bowel vitality after surgery
      remains to be a difficult problem for which second-look-operation was
      recommended. From 1977-1989, 115 patients were operated on AMI (explor.
      laparotomy: n = 28, resection and/or revascularization n = 87). In 36/87
      patients, a planned second look was performed for control of vitality or lavage.
      In 10/87 patients, re-resection was performed, of whom 5 patients survived. By
      the second-look, 6% of 87 patients could be saved. Over all survival was 41.7%.

PMID- 1983565
TI  - [Non-occlusive ischemic enteropathy--diagnosis, differential diagnosis and
      therapy].
AB  - Reduced cardiac output is the pathogenetic principle of non-occlusive disease.
      Prerequisites for early diagnosis include anamnesis, clinical and laboratory
      findings, sonography, mesentericography, contrast enema, and coloscopy.
      Conservative treatment with vasoactive drugs is promising in early stages. As the
      abdominal symptoms develop latently, laparotomy is indicated in most cases in
      order to identify necrosis or perforation and to allow surgery according to the
      intraoperative findings. Despite indisputable progress made during the past
      years, the death rate in our patients (n = 42) is still 43%. Only early diagnosis
      and consequential therapy can achieve better results.

PMID- 1983566
TI  - [Chronic occlusive process of intestinal arteries. Angina abdominalis, surgical
      indications].
AB  - Chronic arterial insufficiency of blood supply to digestive organs in the
      abdominal region is a specific manifestation of circulatory diseases. It is rare
      but may cause substantial danger to the patient. Techniques of vascular repair
      represent an appropriate therapeutic concept, accurate diagnosis and critical
      indication provided.

PMID- 1983567
TI  - [Reconstructive procedures in chronic occlusive processes of the intestinal
      arteries].
AB  - Three approaches are considered: the left thoracoabdominal approach, the right
      sided retro- or supracolic route and the transabdominal access. Aorto-common
      hepatic venous bypass grafting is the preferred procedure in singular occlusions
      of the celiac axis. Reimplantation and aorto-mesenteric venous bypass are the
      treatments of choice in singular occlusions of the mesenteric artery. Occlusions
      of both upper intestinal arteries can be treated with a venous bridge bypass
      graft or by transaortic end-arterectomy. Operative mortality is low (0.9%).
      Remaining occlusion and recurrent symptoms occurred in 12 of 92 patients.

PMID- 1983568
TI  - [Ischemic colitis as a complication after reconstruction of the aortic
      bifurcation].
AB  - Reconstructive surgery of the aortoiliac junction often requires interruption of
      the inferior mesenteric artery. Ischaemic colitis following this type of surgery
      occurs in 15-20% of cases, most often in the splenic flexure and the sigmoid
      colon. It is caused by general haemodynamic factors and/or atherosclerotic
      changes in the intestinal arteries. Clinical symptoms are often subtle or
      atypical and the diagnosis is difficult. However intestinal ischaemia causes
      considerable morbidity and mortality. Around 1000 aortoiliac reconstructive
      procedures were performed, with a 2.8% incidence of post-operative colonic
      ischaemia. The two most important risk factors were hypovolemia and ligation of
      the inferior mesenteric artery.

PMID- 1983569
TI  - [Aneurysms of intestinal arteries].
AB  - Aneurysms of the intestinal arteries are, with an incidence less than 0.1%, rare
      vascular disorders. The aneurysm of the splenic a. is seen in 60% of the cases.
      Next are the hepatic and superior mesenteric a. aneurysm with 20 and 6%. The
      causes are among others mediadegeneration, arteriosclerosis, and infection. The
      most intestinal aa aneurysms are asymptomatic and accidentally discovered by
      angiography. Their importance is given by the risk of rupture, which varies
      between less than 2% and more than 50%. The treatment consists of exclusion with
      or without reconstruction, aneurysmorrhaphy or embolisation. Only the elective
      treatment can prevent a rupture with its high mortality.

PMID- 1983570
TI  - [Celiac artery compression syndrome].
AB  - External compression and kinking of the celiac axis is caused by the enlarged and
      fibrous median arcuate ligament of the diaphragm. The pathogenetic cause may be a
      functional ischemia or an irritation of the squeezed celiac ganglion. This
      painful syndrome is an unusual condition, which occurs at a maximum age of about
      40 years and mostly in women. The diagnosis is established by exclusion of all
      other abdominal sources of pain and lateral aortography. The therapy can often be
      limited to longitudinal incision of the ligament; reconstructive procedures of
      the coeliac artery are sometimes necessary.

PMID- 1983571
TI  - [Superior mesenteric artery compression syndrome].
AB  - Simultaneous compression of the celiac axis and superior mesenteric artery by the
      median arcuate ligament of the diaphragm is likewise uncommon. Only 2 patients
      have been reported in literature. Description of four patients with severe
      abdominal angina caused by this condition. All patients were cured by division of
      the arcuate ligament.

PMID- 1983572
TI  - [Epidemiology and predictability of variceal hemorrhage].
AB  - Up to 80% of patients with liver cirrhosis develop esophageal variceal bleeding
      which is lethal in up to 30% after the first bleeding episode. Parameters
      suitable to identify patients being on risk to bleed from their varices are
      severe liver disease (Child's C), large varices with red color sign and red wall
      markings and high intra-variceal pressure above 12 mmHg.

PMID- 1983573
TI  - [Imaging procedures in diagnosis of variceal hemorrhage].
AB  - Imaging procedures in patients suffering from portal hypertension and the
      problems arising from this condition are limited to the demonstration of the
      morphology of the collateral circulation towards the superior and the inferior
      vena cava. Imaging is essential prior to elective and emergency treatment of
      bleeding varices. Non-invasive and invasive imaging procedures are available.
      Acute hemorrhage of varices usually can not be demonstrated with any of the
      methods. Important is the preoperative evaluation of the portal system and the
      angiographic demonstration of the anatomy.

PMID- 1983574
TI  - [Immediate conservative therapeutic measures in acute variceal hemorrhage
      (including catheter blockage)].
AB  - Balloon tamponade and vasoactive drugs such as vasopressin, glypressin,
      vasopressin and nitroglycerin combined and somatostatin are the mainstay of
      noninvasive emergency treatment of bleeding gastroesophageal varices. However,
      their hemostatic efficacy is limited and recurrent bleeding occurs in at least
      one half of the patients. Survival is not improved. Unwarranted side effects and
      complications may be severe. Therefore, vasoactive drugs and balloon tamponade
      can only serve as temporizing measures until some means of definite control of
      bleeding such as sclerotherapy is available.

PMID- 1983575
TI  - [Sclerosing therapy: technique, indications, results].
AB  - During the last fifteen years, endoscopic sclerotherapy has been established for
      the treatment of bleeding esophageal varices. However, many technical questions
      such as the type of sclerosing agent and the site and schedule of injection still
      exist and require analysis by controlled trials. Endoscopic sclerotherapy has
      been proven effective for the treatment of acute bleeding and for the prevention
      of variceal rebleeding. Improvement of survival by sclerotherapy for the
      prevention of rebleeding, however, is debated. Several controlled trials
      demonstrate that there is no indication whatsoever for the use of endoscopic
      sclerotherapy as primary prophylaxis of variceal bleeding in patients who have
      not bled before.

PMID- 1983577
TI  - [Elective portasystemic shunt: selection criteria, choice of procedure,results].
AB  - The results of conservative medical (propranolol) and endoscopic therapy for
      bleeding esophageal varices show that the surgical shunt is indicated in both,
      acute and elective situations. The portocaval end-to-side-shunt should be
      preferred for hemodynamic reasons. However, special selection of patients is
      required to prevent postoperative liver failure. Linton, Drapanas and Warren
      shunts have a higher recurrence rate, but seem more appropriate for liver
      transplantation candidates. In our own series, preoperative diagnostic shunt
      simulation by balloon-occlusion of the portal vein via an umbilical catheter has
      tremendously improved the results, even for child C-patients.

PMID- 1983576
TI  - [Emergency and early portasystemic shunt: indications and results].
AB  - The definitive hemostasis is the key to successful therapy of variceal bleeding.
      There is a difference between the emergency operation for persistent bleeding in
      spite of initial sclerosing therapy and the planned early operation for primary
      massive bleeding, early recurrence of bleeding and bleeding of fundus varicosis.
      The lethality is about 50% for the emergency operation, about 12% for the early
      operation (Berlin). For the emergency situation the portacaval end-to-side
      anastomosis is favoured. The result of this therapeutical concept in Bonn (1989
      1990) for 47 patients admitted for bleeding was a hospital lethality of 23%.

PMID- 1983578
TI  - [Sequelae and long-term results following portasystemic anastomoses and
      significance of ambulatory after care].
AB  - After portocaval anastomosis 149 cirrhotic patients were treated on an outpatient
      basis. Liver insufficiency was observed in 24%. Encephalopathy was chronic in 14%
      and episodic in 11%. The most common postoperative complication was edema of the
      ankle (48%). Further operations bore a minimal risk (mortality 3/22). Sixty-eight
      percent of the patients agreed to abstain from alcohol; 85% took vacation trips
      and 95% were satisfied with the operation.

PMID- 1983579
TI  - [Surgical measures in recurrent hemorrhage from esophageal and gastric varices
      after sclerotherapy--a prospective study].
AB  - From Jan 1, 1982 to Jan 1, 1990 692 patients were admitted because of acute or
      recurrent hemorrhage from esophagogastric varices. Initial management was
      endoscopic sclerotherapy. 14 pat. were excluded. In 26 of 311 Child-Pugh C
      patients a gastroesophageal disconnection and in 5 because of a portal pressure
      over 30 mmHg a narrow-lumen mesocaval interposition shunt (NLMCS) were performed
      because of uncontrollable hemorrhage. Hospital mortality was 31%. 182 pat.
      belonged to Child-Pugh class A and 185 to B. In 194 long-term injection
      sclerotherapy was successful; 173 were sclerotherapy failures and selected for
      shunt operation at the end of the selection analysis. 85 refused shunt operation
      or did not fulfill selection criteria. Thus, 88 pat. were shunted mainly by NLMCS
      and distal splenorenal shunt. Sclerotherapy and shunt group were comparable.
      Hospital mortality showed no difference. Five year life-expectancy was
      significantly higher in shunted patients. Thus, in sclerotherapy failures early a
      shunt-indication should be discussed.

PMID- 1983580
TI  - [Esophageal varices in childhood].
AB  - A multicenter study over a period of 20 years for 3487 children demonstrated:
      Esophageal varices occur in infants before the age of 6 months (8%). In contrast
      to adults, infants can suffer from intrahepatic biliary atresias and from alpha-1
      antitrypsin-deficiency. Leading to a liver fibrosis and to a hepatofugal
      circulation. This does not always lead to esophageal varices. 15% of all children
      have this asymptomatic follow up. The rest of 85% can be treated successfully
      conservatively and in 15% by sclerotherapy. Further treatment: local thrombectomy
      or familiar liver partial transplantation.

PMID- 1983581
TI  - [Hemorrhage from esophageal varices in non-cirrhotic portal hypertension].
AB  - Non-cirrhotic portal hypertension (NCPH) is a rare cause of bleeding oesophageal
      varices. The prognosis for patients with NCPH is generally better than that of
      patients suffering from cirrhotic portal hypertension. Gastrointestinal bleeding
      or asymptomatic splenomegaly is the usual clinical presentation. If surgery
      becomes necessary splenectomy alone is therapeutically insufficient. Definitive
      reduction of portal pressure by complete or incomplete shunts provide the lowest
      rate of recurrent bleeding and an excellent long-term prognosis. Exact diagnosis
      of the aetiology of NCPH is of great importance in the correct choice of
      operative procedure.

PMID- 1983582
TI  - [Systemic lysis in subacute arterial occlusion].
AB  - The therapeutic regimen used consisted of an ultrahigh streptokinase dosage
      scheme with an infusion rate of 1.5 million units per hour over a period of 6
      hours. Where no immediate clearance occurred or where residual stenoses
      persisted, a catheter dilation (PTA) was subsequently carried out. Favorable
      results were achieved in the group of up to 6 week old femoral occlusions with 2
      or 3 calf arteries open and an occlusion length below 15 cm. Iliac occlusions
      responded well to lytic treatment if a 3 month history was not exceeded.

PMID- 1983583
TI  - [Acute arterial thrombosis: diagnosis and surgical therapy].
AB  - There is an increasing frequency of acute ischemic occlusion due to arterial
      thrombosis; the incidence has a range from 17% to 60%. In contrast to embolism we
      can observe a prolonged therapy less interval due to a lesser dramatic clinical
      course; in thrombotic occlusion only 10% can be treated within 6 h after onset of
      symptoms. In 11 to 93% of all cases extensive and comprehensive surgical
      techniques have to be performed for limb salvage. Nevertheless this aim only can
      be achieved in 60-84%.

PMID- 1983584
TI  - [Local lysis therapy in acute arterial thrombosis].
AB  - Acute thrombotic arterial occlusion is a complication of chronic vascular
      arterial disease. The arteriogram usually reveals a sudden occlusion and the
      collateral vessels. Treatment with low-dose fibrinolytic therapy is widely
      accepted. A combination of low-dose fibrinolysis, aspiration embolectomy and
      angioplasty yields the best primary success rate. In cases of sudden popliteal
      occlusion and dilating arteriopathy ultrasound sonography should be used to
      exclude the presence aneurysm which is a contraindication for fibrinolysis. There
      is a high risk of peripheral embolisation, in the presence of an aneurysm and
      this may cause severe deterioration of the arterial blood supply.

PMID- 1983585
TI  - [Value of intraoperative lysis therapy as an adjuvant measure after late surgical
      embolectomy].
AB  - The effect of intraoperative local fibrinolysis after delayed catheterembolectomy
      (CE) of occluded arteries was examined in a model in the dogs hind limb; the
      superficial femoral artery was occluded by a rapid injection of an autologeous
      blood clot and ligation. Embolectomy was performed 24 h after occlusion with or
      without additional local fibrinolysis (urocinase, r-tPA). The success of
      revascularisation was estimated by measurement of the total periphereal
      resistance. There happened a total re-occlusion in all vessels within 48 h if
      only CE was performed; in contrast after additional fibrinolysis a complete
      revascularisation could be achieved.

PMID- 1983586
TI  - [Diagnosis of deep pelvic and leg vein thromboses by imaging procedures].
AB  - The gold standard for the diagnosis of deep venous thrombosis (pelvis and lower
      limb) is still phlebography--sometimes supplemented by DSA to clarify findings in
      the pelvic region. The indication for phlebography can, however, be markedly
      reduced by noninvasive procedures and restricted to the clarification of
      uncertain findings or the confirmation of the diagnosis for subsequent invasive
      therapy. Ultrasound techniques, particularly color-coded duplex sonography,
      presently appear to take priority among the noninvasive procedures.

PMID- 1983587
TI  - [Fibrinolytic therapy of acute venous thrombosis].
AB  - Fibrinolytic therapy carries a greater risk in the treatment of deep-vein
      thrombosis than mere anticoagulation. It must therefore be considered an elective
      measure in the case of a young patient with extensive thrombotic disease who
      wishes removal of the thrombus in order to reduce his risk of postthrombotic
      sequelae. Regardless the type of fibrinolytic agent used and of the dosage
      employed, one must reckon with a mortality of 1%. One can expect good results in
      80-90% of the patients with fresh thrombi.

PMID- 1983588
TI  - [Clinical and surgical therapy of phlegmasia coerulea dolens].
AB  - Venous thrombectomy was performed on 123 patients with phlegmasia coerulea dolens
      (blue phlebitis). Best results are obtained if treatment is initiated at the
      earliest stage. Arterial involvement must be closely monitored. A fasciotomy,
      which in some cases may involve the fascia lata, must be performed in case of
      compartment compression. Palma's bypass procedure and Av-fistula are indicated in
      some cases.

PMID- 1983589
TI  - [Management of ruptured aortic aneurysms in routine service of a surgical
      department].
AB  - In the year 1989 859 patients with infrarenal aortic aneurysms were treated in
      the Hessen county (5.6 mill inhabitants) (private survey). 64% of the ruptured
      aneurysms were operated in 24 departments for general surgery and 36% were
      operated in the 7 departments for vascular surgery. Corresponding numbers for
      elective operations are 55% respectively 45%. The results after resection of the
      aneurysms in our 22 patients with ruptured aneurysms (1986-1989) reveal a
      letality of 50%. No patient arriving at our clinic alive was excluded from
      operation. Letality in electively operated patients (n = 131) during the same
      period was 2.3% (n = 3).

PMID- 1983590
TI  - [Late results after surgery of ruptured abdominal aortic aneurysm].
AB  - From 1981 to 1989, 695 patients with an infrarenal aortic aneurysm underwent
      surgery. In 114 cases the aneurysm was ruptured. The late results demonstrated,
      that after successful operation a patient's subsequent course was similar to that
      after an elective operation. Infarct and insult were the main causes of death in
      the postoperative period. Sonographic findings complete the postoperation
      analysis of the patient's later course.

PMID- 1983591
TI  - [Aneurysm, dissection and trauma of the thoracic aorta].
AB  - In the last two decades 600 operations for acquired diseases of the thoracic
      aorta were performed at our institution. On the basis of this experience the
      current operative tactics and techniques are outlined. After a initial learning
      phase the early mortality following replacement of the ascending aorta in
      aneurysms and chronic dissection decreased to 4%. Arch replacement now carries a
      risk of 15% as does surgery for acute type A dissection. Descending aortic
      replacement is performed under distal circulatory support and is now associated
      with an early mortality of only 1.6%. In case of severe polytrauma treatment of
      aortic rupture is delayed. Direct suture of the tear often is possible. We
      consider it mandatory for the surgeon to follow these patients in order to
      recognize and treat recurrent aneurysmal disease in due time.

PMID- 1983592
TI  - [Clinical experiences and long-term results after surgical treatment of type A
      thoracic aortic aneurysm].
AB  - For aortic aneurysms type A operative treatment is the method of choice. During
      the past 15 years 128 patients with this diagnosis have been operated on. Early
      mortality was 22%, 77% of all dissections were emergencies. Main causes of death
      were multiorgan failure. Up to 117 months 8 patients died late in part due to
      additional ruptures. 17% of the survivors required reoperation up to 154 months.
      The probability of survival after 10 years is 0.78, in the group with dissections
      only 0.4. Therefore close follow-up of this patient group is necessary in order
      to recognize progression of the disease and induce elective operative treatment.

PMID- 1983593
TI  - [Responsibilities and importance of tumor centers for interdisciplinary tumor
      therapy].
AB  - Early diagnosis, therapy and follow-up of tumor patients rest on the three
      pillars of medical care: tumor centers, hospitals and physicians. The tumor
      centers are the pace makers and coordinators in the following functions:
      definition of primary treatment and additional therapies and their standard of
      quality; implementation of primary multimodal therapies and treatment of rare
      tumors; development of improved treatment methods for tumor metastases and local
      recurrence, including surgical treatment; improvement of diagnostic and
      therapeutic (surgical) potential through interdisciplinary research, especially
      in the fields of tumor biology and tumor immunology; and establishment of a
      standardized follow-up and new care and treatment strategies for the improvement
      of the patients' quality of life.

PMID- 1983594
TI  - [Thoracic aneurysms: criteria for surgical indications and results].
AB  - Elective operations of chronic thoracic aortic aneurysms (TAA) can be performed
      with low risk. In contrast, emergency repair of TAA in symptomatic patients
      including those with rupture is associated with a high mortality. The worst
      results were obtained (a) in patients who were in shock preoperatively, (b) with
      palliative procedures during acute dissection and (c) in patients older than 70.
      The results may be improved by early diagnosis and better operative technique and
      perioperative management.

PMID- 1983595
TI  - [20 years surgery of the thoracic aorta].
AB  - Between 1969 and 1990, 119 patients underwent operations for aneurysmatic disease
      of the thoracic aorta in our department: 63 patients suffered from an aneurysm of
      the ascending aorta, 32 from an acute dissection (26 Type A, 6 Type B), 2 from an
      isolated aneurysm of the arch, 10 from an aneurysm of the descending aorta and 12
      had a traumatic rupture of the aorta. The death rate due to operations for
      aneurysms of the thoracic aorta and acute type A dissections was clearly lowered.
      In case of an acute type A dissection emergency intervention is indicated; in
      acute type B dissection primarily conservative treatment.

PMID- 1983596
TI  - [Dissecting aneurysm of the thoracic aorta. Diagnosis--surgical management-
      results].
AB  - From 1980 to 1989, 84 patients underwent surgery for dissection of thoracic
      aortic aneurysms. According to the DeBakey classification there were 23
      dissections of type I, 35 of type II and 26 of type III. Magnetic resonance
      imaging and combined transesophageal and transthoracic echocardiography are
      highly sensitive and specific methods for diagnosis and followup of aortic
      dissection. 10% of the patients had to undergo surgery again during the first 5
      years. The 5-year-survival rate was 56.1% and the 10-year rate was 40.1%.

PMID- 1983597
TI  - [Surgical treatment of thoracic aneurysms with reference to the Carpentier
      technique].
AB  - Carpentier described Tromboexclusion for treating aortic dissections type B
      claiming lower perioperative neurologic and haemorrhagic complications. We
      performed this operation in 12 exceptional cases with acute (6) and chronic (2)
      type B dissections, 2 patients with aorto-bronchial fistulas and infected grafts,
      and 2 patients with both thoracic and abdominal aneurysm. All patients were in
      haemorrhagic shock and had wall penetration or perforation. In addition to the
      Carpentier operation 3 aorto-subclavian, 2 aorto-bifemoral and 1 renal bypass
      grafts and 1 AVR and 2 ascending aorta replacements were performed. Seven
      patients died perioperatively: 3 because of massive haemorrhage and 4 due to
      pancreatitis and renal failure. Five patients survived the operation, three of
      those died 6-28 months later because of recurrent dissections. One sudden death
      one month after operation is unknown. One patient survived long term. In our
      patients, this operation showed high mortality rates and is therefore rarely
      recommendable.

PMID- 1983598
TI  - [Long-term results of surgical therapy of thoracic aortic aneurysm (dissection of
      the ascending aorta)].
AB  - Thoracic aneurysms are classified according to the nomenclature of De Bakey (1
      3b) or Daily (Stanford A-B). Our early and late results refer to dissections of
      the ascending aorta with and without aneurysms as well as with and without aortic
      valve involvement. The distal extension of the dissections was different. Since
      1979 45 patients (mean age 48 years, range 23-70 years) were operated, the acute
      dissections mostly as emergencies after secured diagnosis. The preferred
      technique was reconstruction of the ascending aorta. However, also other
      techniques as prosthetic replacement or implantation of an conduit were used. The
      hospital lethality was 12.5% (n = 6); the late letality 24% (n = 7). The
      cumulative survival rate after 8 years was 74%.

PMID- 1983599
TI  - [After care and reoperation after primary intervention in chronic type A aortic
      dissection].
AB  - Between 4/78 und 9/89 44 patients (pts.) underwent primary repair of CADA. 3 pts.
      died early postoperatively. 36 pts. were followed-up 3 months to 9.7 years (means
      = 3.1 years) postoperatively with CT, DSA and echocardiography. 8 pts. underwent
      12 aortic reoperations, in 10 cases due to persistent or recurrent aneurysms.
      CONCLUSIONS: In CADA radical replacement of the Ascending Aorta is advisable to
      prevent recurrent aneurysms formation. Systematic follow-up facilitates early
      recognition and repair of progressively chronic or new downstream aortic
      pathology.

PMID- 1983600
TI  - [Aortic aneurysm and aortic injury--surgical treatment and follow-up].
AB  - This study summarizes our experience with 90 patients (68 male and 22 female,
      mean age 57.2 years). From Jan. 1980 to Feb. 1990, 51.1% underwent surgery for
      dissection of the aorta; the rest for acute aortic ruptures, false and true
      aneurysms. Procedures with reconstruction of the aortic arch were performed in
      cases of deep hypothermia and circulatory arrest (no fatal courses). The overall
      death rate was 18.8% (emergency 29.5%, elective 8.7%). Acute dissections Type I
      had the highest perioperative mortality with 29.4%. The leading causes of early
      death were myocardial infarction (23.5%) and cerebral injury (23.5%). Therefore
      coronary angiograms should be performed preoperatively in older patients. A major
      problem in our experience is the long-term followup examination which should
      remain the surgeon's responsibility.

PMID- 1983601
TI  - [Diagnosis and therapy of acute traumatic aortic rupture].
AB  - Aortic transection is defined as complete or partial dehiscence of the aortic
      wall layers. Aortic transections are seen in 16% of all lethal traffic accidents.
      The quality of the first emergency care outside hospital and the organization of
      rescue systems result in an increasing number of patients (espec. with life
      threatening multiple injuries incl. atypical aortic lesions) reaching a trauma
      center. Guide-lines for surgical indications are: 1. emergency-operation in case
      of symptomatic transection incl. simultaneous surgery of concommitant lesions. 2.
      Urgent operation following primary hemodynamic stabilisation in cases of isolated
      or asymptomatic transection. 3. In cases of concommitant lesions with surgical
      priority, delayed operation of asymptomatic transection. The perioperative
      letality claims up to 20%. Next of operative complication paraplegia remains the
      most deleterious problem. Despite different methods of protection on the spinal
      cord the incidence of paraplegia persists in the range of 5-10%.

PMID- 1983602
TI  - [Traumatic segment III aneurysm of the thoracic aorta: surgical risk, technique,
      early and late results].
AB  - Aneurysmectomy was performed in 37 patients with a traumatic aneurysm the aorta
      in segment III. 34 "cross-clamping" without bypass was used, 6 after preliminary
      transposition of the subclavian artery. 3 patients died after surgery, two of
      whom were more than 70 years old. 2 patients developed a paraparesis, which has
      in the meantime considerably improved. Hesitation to operate is justified only in
      older asymtomatic patients at high cardiac risk. Cross-clamping is preferable to
      more elaborate procedures. Preliminary transposition of the subclavian artery
      simplifies the proximal anastomosis and may contribute to spinal-cord protection.

PMID- 1983603
TI  - [What does asymptomatic stenosis mean? Topics in clinical terminology and
      documentation].
AB  - A generally accepted classification and documentation for cerebrovascular
      insufficiency are needed to eliminate controversies and misinterpretation in
      clinical studies on the spontaneous course of the disease and the outcome of
      patients receiving surgical or conservative treatment. The author proposes a
      clinical classification (stages I to IV) based on the affected vascular territory
      (A, B, C). The following findings should be included: 1. the number of diseased
      extracranial arteries (I to IV vessel disease), 2. the presence of ischemic brain
      lesions (CT, SPECT, RMI), 3. concomitant diseases or risk factors (hypertension,
      coronary heart disease etc.). Such morphological and functional staging makes
      possible the selection of comparable groups of patients for investigation.

PMID- 1983604
TI  - [Critical stenosis of the internal carotid artery--which parameters determine
      prognosis?].
AB  - Neurologic symptoms in the region of an internal carotid artery stenosis are due
      to emboli or the reduction of perfusion pressure. Measurements of cerebral blood
      flow correlate with perfusion pressure but not with the degree of the stenosis.
      By transcranial ultrasound sonography the reactivity of the cerebral vascular
      system can be measured. Thus subgroups of patients may be found who may or may
      not benefit from the operation. By analysis of color coded duplex sonography,
      ulcerated stenoses can be detected with high accuracy.

PMID- 1983605
TI  - [Asymptomatic carotid stenosis: which preoperative diagnosis is necessary and
      adequate?].
AB  - Operative correction of asymptomatic ICA stenosis requires only CCT and
      intraarterial DSA of all the common noninvasive procedures. Multiple vessel
      disease, however, must also be examined by quantitative cerebral blood flow
      measurements to determine the autoregulation reserve capacity; this can be done
      by transcranial Doppler plus CO2 provocation or rCBF with carboanhydrase
      inhibitor. CCT or NMRI seems necessary in any case. Detailed cardiac examination
      is absolutely necessary in all carotid patients.

PMID- 1983606
TI  - [Therapeutic concept in asymptomatic carotid stenosis: surgical indications from
      the neurologic viewpoint in comparison with spontaneous course].
AB  - The annual risk of stroke from asymptomatic carotid stenosis is about 0.5-2.5%.
      After successful carotid endarterectomy (CEA) the risk of suffering a stroke
      amounts to about 2% per year. CEA therefore seems to impose an unnecessary risk
      upon the patient. However, a stenosis with more than 80% luminal narrowing, a
      rapidly progressing stenosis, and ulcers may increase the spontaneous risk and
      should be evaluated in randomized studies. The same applies to prophylactic CEA
      of asymptomatic stenosis before major cardiac or vascular surgery.

PMID- 1983607
TI  - [What are the prerequisites for surgery of asymptomatic carotid stenosis?].
AB  - Asymptomatic patients with carotid stenoses exceeding 75% have an elevated
      ischemic cerebrovascular event rate of 18% per year (5% strokes). Our combined
      perioperative stroke and death rate (1980-1990: 1123 operations) is 1.85%. Thus
      prophylactic surgery may be indicated in the following cases: hemodynamically
      significant stenoses of 75% and more, especially with marginal or reduced
      autoregulatory reserve, rapidly progressing lesions in medically treated
      patients, lesions with a high risk of embolization (ulcerations on B-scan), clear
      interrelation between arterial lesions and positive (asymptomatic) intracranial
      findings (CT, NMR, TC, USD).

PMID- 1983608
TI  - [Advantages and problems of interdisciplinary tumor conferences].
AB  - Interdisciplinary cancer conferences (ICC), which deal with the problems of
      individual patients, are an appropriate instrument for coordinating
      interdisciplinary decisions at an early stage and for ensuring adherence to
      standard diagnostic and therapeutic procedures. As shown by seven-years
      experience and data from 1225 cases, about 80% of the decisions made by the
      conference are followed by the responsible physician. Regular meetings at
      suitable times and locations, effective preparation with information about the
      problems to be discussed and rapid distribution of written reports to all
      participants will guarantee a continuing interest in presenting patients at the
      ICC.

PMID- 1983609
TI  - [Surgical treatment of asymptomatic carotid stenosis].
AB  - A total of 274 patients (mean age 67.1 +/- 8.2 years) with asymptomatic stenosis
      of the internal carotid artery greater than 70% was treated by desobliteration
      and patchplasty; 332 reconstructions were performed either uni- or bilaterally.
      In this group only 29% revealed a one vessel disease. Lethality within 30 days
      was 1.5%; the incidence of complete stroke amounted to 0.9%. In a mean follow up
      period of 30.8 +/- 20.2 month to lethality rate was 4.4%; 7.8% developed a
      completed stroke and only 3.8% were related to the operated site. The 5-year
      survivalrate was 88.9% and 93.2% of this cohort was neurological free of
      symptoms.

PMID- 1983610
TI  - [Postoperative results of treatment in comparison with results of the German
      prospective randomized CASANOVA Study].
AB  - Independent of the results pending from the postoperative randomized German
      multicenter trial (CASANOVA Study), in which the course of operative versus non
      operative treatment of asymptomatic carotid artery stenoses is being compared,
      there is still a clear justification for operative desobliteration if the
      following criteria are fulfilled: 1. Severe carotid stenosis with hemodynamic
      significance is proved by an extremely reduced or abolished autoregulatory
      reserve in the transcranial Doppler CO2-test. 2. Lesions with high embolic risk
      are confirmed by arteriography or B-Scan sonography. In 744 patients who
      underwent surgery according to these prerequisites there was a mere annual stroke
      rate of 0.2% during a followup of up to 18 years. This means that in comparison
      with the results of non-surgical therapy (annual stroke rate 1-3%) the risk of
      stroke was reduced by tenfold.

PMID- 1983611
TI  - [Need for surgery in asymptomatic carotid stenosis].
AB  - 1. Asymptomatic carotid stenosis up to 80% do not require prophylactic surgery,
      but should be followed non-infasively. 2. Stenoses of 80-99% are associated with
      a significant incidence of stroke which is estimated to be 4-10%/year. 3.
      Occlusion is considered to be an unfavorable end point, since the risk of stroke
      remains higher than those with patent arteries. 4. The role of carotid
      endarterectomy is related to the stroke morbidity and mortality of the procedure.
      To show significant benefits of surgical therapy during the first two years, it
      is necessary to have a stroke/death rate of less than 3%.

PMID- 1983612
TI  - [Simultaneous carotid endarterectomy and coronary artery bypass. when is it
      indicated?].
AB  - In cases of concommitant coronary heart disease (CHD) and carotid artery stenosis
      (CAST) simultaneous correction has a higher risk. Transcranial Doppler flow
      measurements at the level of the arteria cerebri media did not detect any flow
      reduction during open heart surgery in patients with and without carotid lesions.
      New neurologic deficits during open heart procedures are mostly due to embolism
      from ECC or from the heart, rather than a high grade carotid stenosis.
      Simultaneous correction of CHD and CAST is only indicated in patients with
      severely unstable angina and symptomatic high grade stenosis of the carotid
      artery.

PMID- 1983613
TI  - [Modification of non-hemispheric symptoms by carotid endarterectomy].
AB  - In case of multi-locular supra-aortic lesions the correction of a hemodynamic
      carotid stenosis has priority over any reconstruction of another supra-aortic
      lesion. Thus carotid endarterectomy leads to an improvement of the global
      cerebral perfusion. Patients with a classical vertebro-basilar insufficiency
      profit most by these operations. A subclavian or vertebral reconstruction or PTA
      is indicated only if the patient is not symptom-free after the carotid
      endarterectomy.

PMID- 1983614
TI  - [Surgery for asymptomatic carotid stenosis: a contribution to a controversial
      discussion].
AB  - From 1 January 1982 to 30. June 1986, 436 operations on the internal carotid
      artery were performed: 164 were asymptomatic (37.6%). Morphologic indication was
      stenoses greater than 70% only. Supra-aortic multivessel disease played a major
      role. The operative mortality amounted to 0.6% (total 0.9%) and the perioperative
      mortality, 1.8%. The cumulative morbidity was 1.6% after the first and 1.8% after
      the second year, whereas the cumulative survival rate measured 89.8% after one
      and 80.4% after three years. Therefore surgery for asymptomatic carotid internal
      stenoses is justified under conditions of the restrictive indication. It also
      seems to be more favorable as regards early and late results.

PMID- 1983616
TI  - [Lung injuries: diagnosis and surgical strategy].
AB  - Between 50 to 60% of all polytraumatized patients have a thoracic injury with a
      mortality of 30 to 60%. The first diagnostic steps involving symptoms such as in-
      or expiratory pain, emphysema of the skin, flail chest or sipping noise lead via
      clinical examination to first and often definitive therapeutic procedures, i.e.
      intubation, artificial respiration and insertion of chest tube. X-ray of the
      chest, computed tomography as well as ultrasonic screening and monitoring of
      arterial blood gases are important in in-door technical diagnosis. The decision
      for emergency room thoracotomy or a regular or delayed operation has to be made
      at times. Complications (20%) to consider are pneumo- and haematothorax, pleural
      rind, pneumonia, broncho-pleural fistula and most of all pleural empyema.

PMID- 1983617
TI  - [Cooperation between the pathologist and surgeon in modern cancer surgery].
AB  - Management of up-to-date cancer therapy in strict accordance with histology and
      stage warrants more than ever a competent co-operation of the pathologist. For
      this reason the surgical pathologist has to act in dual roles as a diagnostician
      and consultant. With reference to the internationally acknowledged histological
      grading and classification of malignant tumors and further the refined principles
      of the TNM-classification, diagnostic requirements for surgical pathology have
      considerably been extended in the field of interdisciplinary oncology.

PMID- 1983615
TI  - [Organ injuries--introduction].
AB  - Organ injuries are a frequent occurrence: The Surgical Department of Wuerzburg
      University treated 270 patients between 1983 and 1987. More than one-fifth of
      these patients had undergone primary surgery at other hospitals and came to us
      for reoperation or intensive care. The successful treatment of such severe and
      often multiple, simultaneous injuries depends on well-trained surgeons whose
      undelayed consultation with specialists is not impeded by bureaucratic hospital
      organization.

PMID- 1983618
TI  - [Heart injuries: diagnosis and therapy].
AB  - The clinical manifestation of wounds of the heart is determined by the mode, site
      and size of the injury as well as the structure of the pericardial and myocardial
      lesion. Diagnosis can be confirmed by ECG and echocardiography. Only 20% of the
      patients with penetrating wounds of the heart live for more than 30 minutes.
      Pericardio-centesis should be used only to gain time for a safe sternotomy,
      cardiac decompression and suture of the wound of the heart. An aggressive
      surgical approach is mandatory. Cardiopulmonary bypass is necessary only to
      correct of concomitant lesions.

PMID- 1983619
TI  - [Diaphragmatic injuries, classification and therapy].
AB  - Injuries of the diaphragm are caused either by direct or indirect violence. In
      all such ruptures various portions of the abdominal viscera may have ascended
      into the thoracic cavity. The clinical manifestations are unpredictable and of
      infinite variety, and especially in massively traumatized patient masked by other
      injuries. A presumptive preoperative diagnosis of diaphragmatic injury from chest
      x-ray findings is only possible in about 50% of the cases. In other cases the
      diagnosis can be confirmed by water.soluble contrast enema into the stomach or
      colon. Rupture of the diaphragm is a strong indication for operation. In cases of
      fresh rupture we attempt repair of the diaphragm through a laparotomy incision.
      In old diaphragmatic rupture we prefer a thoracotomy incision.

PMID- 1983620
TI  - [Blunt abdominal trauma: practical diagnostic strategy].
AB  - The principal aim of a practical diagnostic strategy is rapidly identify the
      organ injury following blunt abdominal trauma. A general diagnostic strategy and
      special technical investigations are described and their relative values
      discussed. From 1 January 1986 to 31 December 1989, 440 patients were treated for
      blunt abdominal trauma which had resulted in 166 organ injuries. Ultrasound was
      used in the initial investigation. Its sensitivity was 96% and specificity 98%.
      Following examination by ultrasound the rate of negative laparotomies was 1.3%.

PMID- 1983621
TI  - [Splenic injuries: diagnosis and therapy (with reference to organ
      saving/replantation)].
AB  - Diagnosis of splenic injury is influenced by both the type of injury and the
      diagnostic possibilities at the place of evaluation. Noninvasive examination with
      ultrasonography, computed tomography, or radionuclide scanning detects the
      injury. If not available diagnostic peritoneal lavage can indicate the necessity
      of laparotomy. Splenic salvage is the treatment of choice in splenic injury.
      Selective non-operative treatment of blunt trauma, splenorrhaphy, and partial
      splenectomy were used successfully to preserve 67% of injured spleens. Clinical
      and experimental findings indicate that replantation of splenic autologous tissue
      will not protect the host from septicemia.

PMID- 1983622
TI  - [Stomach, duodenal and pancreatic injuries: diagnosis, surgical procedure].
AB  - Whereas ruptures of the spleen and liver are comparatively frequent, traumas to
      the pancreas, stomach and duodenum belong to the rarities. Thus, observed in our
      own patient material from 1982 to 1988, out of 218 surgically treated patients
      with a blunt abdominal trauma, we found only 1 duodenal rupture, 1 rupture of the
      stomach and 5 injuries to the pancreas. Diagnostics and therapy however can raise
      considerable problems. The indication for surgery is obtained clinically, the
      peritoneal lavage being the most important diagnostic procedure. Whereas
      treatment of a gastric rupture is not a problem, treatment of a duodenal rupture
      depends on the type of rupture. Lesions to the pancreas carry a bad prognosis
      depending on the degree of seriousness. Mortality is high ranging between 10 and
      20%. Therapy depends on the degree of seriousness and has to be limited to a
      drainage operation in the individual case.

PMID- 1983624
TI  - [Kidney and bladder injuries: diagnosis and therapy].
AB  - Classification of renal trauma is given. Perforated trauma requires operation,
      blund trauma is treated conservatively, at least in stage I and II. Severe
      hemorrhage is reason for surgical exploration and nephrectomy in stage III and IV
      renal trauma. Renal trauma is best diagnosed by sonography and CT-scan. Bladder
      trauma is best diagnosed by cystogram and classified to intraperitoneal leasons
      which require immediate operation and to extraperitoneal leasons which are
      treated conservatively.

PMID- 1983623
TI  - [Injuries of the small and large intestine].
AB  - While laparotomy is always mandatory for penetrating injuries of the intestine,
      its indication for blunt trauma is still difficult because of diagnostic
      problems. Late interventions are responsible for a poor prognosis in these
      patients. While the operative management of small bowel ruptures is mostly
      unproblematic injury of the large intestine demands more differential treatment.
      In cases of contaminated abdominal cavity and the necessity of bowel resection a
      so-called anastomosis stoma should be used if possible. In case of major trauma
      of the rectosigmoid, a Hartmann procedure may be necessary. Profuse drainage and
      colostomy are required in cases of trauma of the extraperitoneal part of the
      rectum.

PMID- 1983626
TI  - [Accident mechanisms and classification in distal radius fracture].
AB  - The form and severity of fracture of the distal radius as well as the concomitant
      injury of discoligamentary structures of the wrist depend on the position of the
      wrist at the moment of hitting the ground. The width of this angle influences the
      localization of the fracture. Pronation, supination and abduction determine the
      direction of force and the compression of the carpus and the different
      appearances of ligamentary injuries. The classifications of these fractures
      published by Frykman (1967) and M. E. Muller et al. (1989, AO-Group), incomplete,
      are useful for objective evaluation or documentation and may suggest indications
      for treatment when critically used.

PMID- 1983625
TI  - [Intraoperative autotransfusion in massive hemorrhage after thoracic-abdominal
      trauma].
AB  - In the University Hospital of Granada (Spain), 359 trauma surgical patients
      underwent intraoperative autotransfusion. Patients from group I (blood loss less
      than 2000 ml) did not requiere homologous blood transfusion. So the high risk
      involved in the type of transfusion was avoided. With patients from group II,
      however, that is, those with a blood loss of more than 2000 ml, we had to fall
      back on homologous transfusion in addition to retransfusing autologous blood. The
      main indication for intraoperative autotransfusion is without doubt abdominal and
      thoracic trauma which lead to high blood loss.

PMID- 1983627
TI  - [Indications, technique and preventable errors in conservative therapy of distal
      radius fracture].
AB  - The guidelines for conservative or operative treatment of fractures of the distal
      radius have been standardized for years. To decide whether conservative treatment
      is indicated the following factors are important: 1. the amount of metaphyseal
      impaction, 2. the presence of a joint surface, and 3. the remaining bony
      buttress. Conservative treatment is indicated in cases in which there is a chance
      to ensure retention. The difficulty of conservative treatment does not lie in
      special sophisticated steps of procedure. It is more important to consider the
      standardized technical procedures of reduction, adequate immobilization and
      surgical control.

PMID- 1983628
TI  - [Treatment of distal radius fracture. Surgical technique: bore wire
      osteosynthesis].
AB  - The Kirschner wire fixation is mainly indicated in unstable types of Colles' and
      children's fractures of the distal radius. Out of 2760 distal radius fractures
      (1975-1989) 626 (20.7%) were treated operatively including 326 (11.8%) with K
      wires. Primary operation was performed in 53.5% immediately after trauma.
      Exposing the sensitive radial nerval paths, 3-4 K-wires were inserted from the
      radial and the dorsoulnar aspect. The K-wire ends were covered subcutaneously.
      The clinical evaluation of a series of 226 patients according to the score of
      Lidstrom presented 79% excellent and good, 16% fair and 5% poor results. The
      clinical results correlate to the radiocarpal angle and radial shortening.
      Because of additional injuries to the ulnar complex give worse results in
      reposition, the ulnar styloid should be fixed.

PMID- 1983629
TI  - [Responsibilities of biostatistics for evaluation of treatment results in tumor
      therapy].
AB  - Besides randomized controlled clinical trials the careful prospective data
      collection in a clinical databank or registry is an important tool in assessing
      surgical treatments in cancer therapy. It is shown that the application of
      multivariate statistical methods is important in analyzing such data.

PMID- 1983630
TI  - [Treatment of distal radius fracture with plate osteosynthesis].
AB  - The indications for osteosynthesis of distal radius fractures with a T-plate have
      been precisely defined. They include Smith's fractures, Barton's fractures,
      reversed Barton's fractures and the fracture types A3, C1 and C2 according to the
      A0 classification. The surgical approach is dorsal for the extension type
      fractures and palmar for those of the flexion type A. Correct diagnosis and
      accurate operative technique make it possible to achieve favourable results in
      the treatment of these often compound fractures. Results are presented for 105
      patients who underwent osteosynthesis of distal radius fractures with a T-plate.

PMID- 1983631
TI  - [Advantages and disadvantages of various kinds of anesthesia in reposition of
      distal radius fracture].
AB  - The fundamental differences of general anesthesia and somatic blockade have to be
      considered. When selecting the method of anesthesia to reduce distal fractures of
      the radius. Brachial plexus block and local anesthesia within the therapeutic
      dose of the drug leave vital centers intact and metabolism undisturbed. Somatic
      blockade can be applied without further investigations when urgency is indicated.
      If an anesthesiologist is not present, the surgeon can apply the method.
      Experience reduces the rate of drawbacks.

PMID- 1983632
TI  - [Special forms of distal radius fractures].
AB  - The severity of a fracture of the distal radius is not only determined by the
      type of the fracture but also by concomitant ligamentous and carpal injuries,
      which are often underestimated and imply a higher degree of instability than the
      bony lesion alone. Therefore classifications are valuable, which combine fracture
      type and associated lesions, thus permitting conclusion about the therapeutic
      method of choice. The article discusses indication, operative technique and
      special features of radial fractures in combination with carpal injuries, of
      radial styloid fractures as well as Barton's and Reverse-Barton's fractures, of
      bilateral radial fractures and of radial fractures as part of a chain fracture.
      It is important to perform an early fasciotomy and carpal tunnel release in cases
      of severe soft tissue damage and threatening compartment syndrome.

PMID- 1983633
TI  - [Pediatric fractures of the distal radius].
AB  - Fractures near the wrist account 3/4 of all forearm fractures. In most cases both
      of the forearm bones are fractured. A distal fracture of the radius, comparable
      to the radius fracture in loco typic of adults, does not occur in children for
      several reasons. Treatment with preliminary extension has shown benefits only in
      those cases, in which both forearm bones were fractured. Axis deviation of more
      than 10 degrees and an ad latus dislocation of more than 1/4 of the bone diameter
      must not be tolerated. The importance of the distal radioulnar joint as well as
      possible scar formation of the membrana interossea must be stressed. More than
      80% of forearm fractures can be treated conservatively with good results. The
      other 16.5% must be treated operatively. The applied procedures also yield good
      and very good results in more than 90% of the cases.

PMID- 1983634
TI  - [Physical therapy treatment of distal radius fractures].
AB  - Physiotherapy of fractures of the distal radius is a concomitant treatment, not
      only after-care, of conservative and operative fracture therapy. Its aim is to
      avoid muscular atrophy and contraction and to improve circulation. For these
      reasons physiotherapy should begin shortly after fracture treatment and should
      include active mobilisation of the fingers, the elbow and the shoulder joints, as
      well as isometric exercises and neurophysiological physiotherapy. Physicotherapy
      (local ice treatment, electrotherapy, ultrasound treatment) can support
      physiotherapy.

PMID- 1983635
TI  - [Treatment of distal radius fracture--diagnosis and therapy of local concomitant
      injuries].
AB  - In a high percentage the accompanying local injuries in Colles' type fractures of
      the distal radius are related to lesions of the triangular fibrocartilage complex
      (TFCC) and the distal radioulnar joint (DRUG). Frequency and importance of these
      local injuries concerning the long-term result after distal radius fractures are
      described and diagnostic and therapeutical proceedings are presented.

PMID- 1983636
TI  - [Imaging procedures in abdominal tumors].
AB  - The value of imaging modalities in abdominal malignancies is discussed.
      Ultrasound is the first method to perform in hepatic tumors--HCC and liver
      metastases--, followed by CT and/or MRI. CT and ERCP are the diagnostic
      procedures of choice in pancreatic cancer. MRI is inferior to bolus-enhanced CT.
      CT and MRI are still equal in colorectal cancers for differentiating between scar
      and local recurrence after abdominal-perineal amputation.

PMID- 1983637
TI  - [Malposition and corrective interventions after distal radius fractures].

PMID- 1983638
TI  - [Sequelae and evaluation after distal radius fractures].
AB  - The sequela of fractures of the distal radius show the same variety as the
      fracture models themselves, depending on conservative or operative repositioning.
      The most frequent disadvantages are deviation of the bone axis, depression of the
      basis of the radius, steps in the cartilage plain and rough deformity. Most
      important are the arthrotic changes in the joint, such as entrapment and
      compression neuropathies. The sequela of fractures in children, adults and the
      aged differ. The purpose of the expert appraisal is not only to assess the
      damages after fracture but also to give new proposals for further therapy.

PMID- 1983640
TI  - [Fractures of the mid-hand area--classification, management, results and
      problems].
AB  - Of the various types of hand fractures, metacarpal fractures occur quite
      frequently, predominantly in younger people. In order to maintaining hand
      function man's most important tool, the treatment of coice in recent years has
      shifted from predominantly conservative measures to more surgical procedures.
      From 1980 to 1988, 33 patients with metacarpal fractures were treated: 66%
      received surgical and 34% conservative treatment. We report on the results as
      regards hand function, the length of unemployment, the patient's subjective
      complaints and the peri- and postoperative complications.

PMID- 1983639
TI  - [Fresh fractures! Classification, management, results and problems: the wrist
      joint].
AB  - Carpal bone fractures are rare, with an incidence of 13% compared to that of
      fractures and luxations of the hand bones. Generally they are intraarticular
      fractures. Fracture of the scaphoid bone occurs most frequently, with an
      incidence of 75%. The greater number of fractures is found in the middle-third of
      the wrist bordering on the os lunatum. They are usually treated conservatively by
      splinting with a cast. Surgery is indicated only when the fracture is open,
      instable, dislocated or combined with carpal instabilities.

PMID- 1983641
TI  - [Treatment of phalangeal fractures].
AB  - Due to anatomical reasons the therapy of phalangeal fractures is a domain of
      conservative treatment in contrary to metacarpal fractures. Special attention
      must be focused on defective position in axis and rotation of the fractured
      phalanx. We use the Iselin splint. The indication for operation depends on the
      patients compliance, the type of fracture and its localisation. Indications for
      operation in our opinion are open fractures, dislocated, non reponible fractures,
      fractures involving the joint, condylar fractures. Conservative treatment gains
      the more importance the more the fracture is localized at the end of the phalanx.

PMID- 1983642
TI  - [Significance of primary diagnosis of carpal instability].
AB  - In general the dislocation of the carpal bones with subsequent carpal instability
      is rare. The diagnosis depends on a correct interpretation of the X-ray. In a
      follow-up study 25 patients with closed carpal instabilities were examined. In 14
      the carpal instability had been established in the primary diagnosis and treated
      adequately. The functional results were good. 11 patients, in whom the
      dislocation of the carpal bones had been overlooked, did not receive primary
      therapy and had unsatisfactory function of the hand.

PMID- 1983643
TI  - [Cinematography, a new diagnostic procedure in evaluation of the injured painful
      wrist joint].
AB  - By the X-ray Cineradiografie we are able to examine and to judge the dynamic of
      the wrist bones by 50 pictures/sec. in comparison to one another and also
      depending on their ligaments. We did an investigation of 170 patients with
      painful wrist. With the method we were able to make up a clear diagnosis and to
      propose the therapy. I.e.: If consecutive shortening of the radius after distal
      radius fracture resulting ingruency of the wrist joint is relevant, or a scaphoid
      pseudarthrosis is fixed elastically, or a scaphoic dissociation is effective. The
      variations were shown in comparison to normal circumstances.

PMID- 1983644
TI  - [Scapholunar dissociation--when an accident sequela, when a normal congenital
      variant?].
AB  - The scapholunate dissociation is an instability of the wrist which shows
      characteristic signs in the X-rays. It is commonly believed to be caused by
      trauma. During the past two years four cases of idiopathic scapholunate
      dissociations were identified by the typical radiologic signs on both sides
      without any trauma or symptoms. Before operative treatment of an injured hand X
      rays of the uninjured side should be examined.

PMID- 1983645
TI  - [Fresh extensor tendon injuries of the forearm and hand (management, results and
      problems)].
AB  - 1944 patients with 2418 lacerations of extensor tendons in the hand were treated
      since 1966. Follow up study was possible in 1031 (53%) patients. The discussion
      about the best method to evaluate the results of treatment lead to a better
      scheme for critical examination. The preoperative status was taken into
      consideration as well as the subjective meaning and brought into harmony with the
      objective results.

PMID- 1983646
TI  - [Fresh nerve and vascular injuries of the forearm and hand (management, results
      and problems)].
AB  - Lacerations of arteries and nerves not only result in motor and sensory
      deficiencies. Trophic changes occur as well, more frequently after nerve injuries
      than after vascular injuries. The major progress in their treatment consists in
      primary repair of the injured structures in order to keep their loss of function
      as brief and as minimal as possible. Although the results after nerve laceration
      are still far from being ideal, there are strong indications that an improvement
      can be obtained with this treatment strategy. Alternatives to primary repair are
      discussed.

PMID- 1983647
TI  - [Fresh post-traumatic soft tissue defects of the wrist joint and hand and their
      closure].
AB  - As a universal human tool the hand often suffers injuries of its soft tissue.
      Different localization of defects (palmar and dorsal) and different injuries of
      functional structures (tendon, nerve, vessel, bone) also need different soft
      tissue cover and wound closure. The possibilities in plastic surgery of the hand
      include free transplantation of skin, local and distant flaps, free flaps and
      neurovascular flaps.

PMID- 1983648
TI  - [Status of replantation--indications and limits in hand surgery].
AB  - Replantation of severed fingers or hand segments has become a routine procedure.
      Up to now the following clinical conditions are accepted as clear indications: 1.
      Amputation at the wrist or metacarpal level. 2. Amputation of several fingers. 3.
      Thumb amputation. 4. Amputation in childhood. 5. Special hand functions. Our
      clinical results in 1123 patients suffering from 973 total and 899 subtotal
      amputations are presented. Due to frequent employment of micro-venous
      interposition grafts success rates of about 80% could be obtained even in cases
      of crush or avulsion injuries. Recommendations concerning the improvement of the
      operational conditions and functional rehabilitation are discussed.

PMID- 1983649
TI  - [Primary and secondary soft tissue injuries of the hand and therapeutic
      possibilities].
AB  - Primary treatment of soft tissue hand injuries is most important for further
      management and progress. It ensures best protection of lower structures. Soft
      tissue lesions that can not be closed without resulting tensions need instant
      plastic-surgical therapy. Various possibilities that range from split skin flaps
      to distant flaps with microvascular anastomosis can be chosen to cover primary as
      well as secondary soft tissue defects.

PMID- 1983650
TI  - [Thumb replacement operation using metacarpal distraction osteotomy as a
      secondary intervention after thumb amputation].
AB  - After thumb amputation distal to the MCP-1 joint, good results can be achieved
      with lengthening of the first metacarpal bone by an external fixateur if a
      correct technique is applied. In all our patients the lengthened thumb was
      mechanically stable and sensitive, thus improving the patient's ability to use
      the hand to grasp. Another advantage of this procedure is the relative simplicity
      of the method. Furthermore, the original nerve and vascular supply can be
      preserved.

PMID- 1983651
TI  - [Saw injury of the hand--an accident with grave sequelae].
AB  - Besides bruises saw injuries of the hand are the most common severe hand
      injuries. A total of 294 of 400 patients who had a saw injury between 1982 and
      1986 were monitored in the course of a followup examination spanning the time of
      the accident up to re-entry into professional life. Causes of accidents as well
      as injury patterns, surgical treatment and aftereffects were analysed. The high
      number of injuries (70.8%) sustained while not working was remarkable as well as
      the fact that despite the seriousness of the injury 64.6% of the patients were
      content with the cosmetic results of treatment and 65% satisfied with the
      recovered function of the injured hand.

PMID- 1983652
TI  - [Metastasis in lung and pleura].
AB  - The Topography, extent and histopathology of lung and pleural metastases in 132
      surgical resections were investigated with regard to primary tumours. The
      emphasis was on postmortaly obtained angiographic results of the
      neovascularisation of metastases, mainly by vessels of the functional pulmonary
      circulation with diameters of 20-60 microns. Different phases of metastatic
      spread were considered such as invasion, embolisation and implantation. The
      pathologic-anatomic investigation of metastases is becoming more and more
      important for morphological quantification of tumour regression following
      cytostatic therapy and for clarifying unknown primary tumours by the
      immunohistochemical examination of lung metastases.

PMID- 1983653
TI  - [Surgical therapy of breast cancer].
AB  - The surgeon's leading role which he plays in the changing concept of primary
      breast cancer treatment is described. To apply breast conserving therapy a number
      of prerequisites must be fulfilled. As compared to mastectomy, there are still a
      number of problems connected with this treatment modality. Therefore, it remains
      doubtful whether the latter can already be regarded as standard treatment. For
      the future, reducing breast cancer mortality as well as treatment
      individualization remain the major goals.

PMID- 1983654
TI  - [Special diagnosis of pleural metastasis].
AB  - In 58% of cases diagnosis of pleural metastases is confirmed by identification of
      malignant cells in pleural effusions. Sensitivity of pleural punch biopsies
      ranges about the same. Combination of both methods increases success rate up to
      75%. Thoracoscopy has a sensitivity of about 89%, charged with complications in
      1.7%, and over-shadowed by a lethality of 0.08%. Classical thoracoscopy after
      Jacobaus has to be differentiated from Maassen's method, using the
      mediastinoscope. Highest success rates are achieved by means of diagnostics
      thoracotomy, which in fact is restricted to isolated cases, where previous
      methods proved unsuccessful.

PMID- 1983655
TI  - [Technique and results of surgery for lung metastasis].
AB  - Surgical treatment of pulmonary metastases is part of an interdisciplinary
      strategy in oncological therapy. Between 1973 and 1989, 620 thoracotomies were
      performed in 549 patients. The most profitable access was the median sternotomy.
      Thirty-day mortality was 2.7%, 5-year survival was 30% for all patients. If the
      resection was classified as potentially curative, 5-year survival was 35%.
      Patients with pulmonary metastases of testicular tumors (5-year-survival rate
      70%) had the best prognosis. Prognostic factors must take the primary tumor into
      consideration.

PMID- 1983657
TI  - [Treatment of pleural metastases in an interdisciplinary concept].
AB  - A retrospective examination involved 414 patients (260 m, 154 w, mean 60 y) with
      pleural metastasis/pleural effusion of the following primary tumors: 37.2%
      bronchogenic (23.2% malignant pl. mesothelioma), 14.5% breast, 8.7% adeno-ca
      (unknown primary) 2.4% gastrointestinal, 2.2% uterus/ovar, and 11.8% others.
      Thoracoscopy with histologic confirmation played a central role in our diagnostic
      procedures in 97% of the cases. Malignancy was defined by CEA (less than 5 mg/ml)
      (71.9%) and cytology (76.9%) in 90.4%. Our strategy had the following success
      rate: desiccation by pleural drainage (greater than 26 Charr) alone 74%, in
      combination with pleurodesis 81%, pleurectomy/decortication 95%, and extended
      pleuropneumonectomy (in 80% mesothelioma) 96%.

PMID- 1983656
TI  - [Parietal pleurectomy in pleural cancer].
AB  - Exudative pleural carcinosis may remain the only localisation of generalized
      disease for months. Exudation and total distension of the lung must be prevented.
      Since sclerosis is not effective in cases of tapered lung, parietal pleurectomy
      and decortication are indicated. This ensures patient survival and fitness for
      work for several years.

PMID- 1983658
TI  - [Surgical treatment and prognosis of lung metastases].
AB  - From 1979 through 1988, 215 patients with pulmonary metastases were treated in
      our department. Surgery was possible in 112 patients. Eighty-two patients were
      resected curatively, whereas 30 had only palliative surgery. The operation
      mortality was 1.8%. The essential prognostic factors were the complete removal of
      all pulmonary metastases, the portal or caval path of metastasis, involvement of
      the hilus lymph nodes and presence of clinical symptoms upon hospital admission.
      The 5-year-survival rate of patients undergoing potentially curative operations
      was 31%. This was significantly higher than in patients who underwent palliative
      operations (9%).

PMID- 1983659
TI  - [Long-term results of surgical treatment of lung metastases].
AB  - A retrospective review covered 110 patients who had had 130 thoracotomies for 193
      lung metastases between 1960 and 1988. The cumulative survival rate after 5 years
      was 39%, 24% after 10 years and 13% after 15 years. The median survival was 3.8
      years; the average survival was 7 years. In a multivariate analysis, response to
      prior chemotherapy, local tumor extent (intrapulmonary versus extrapulmonary
      disease) and venous drainage (caval versus portal) were the most important
      prognostic factors. The number of metastases and the interval between primary
      tumor and lung metastases were of minor prognostic importance.

PMID- 1983660
TI  - [Developments in surgery of pulmonary metastases].
AB  - Two groups of patients between 1977-1986 and 1987-1989 underwent surgery for
      pulmonary metastases. The most frequent primary sites were the kidney and the
      colon-rectum. While metastases from testicular cancer have become rare
      indications, metastases from breast cancer are increasing. Our results show that
      more metastatic lesions are usually found at operation than indicated by CT scan.
      The discrepancy amounts to 18% in presumably solitary metastases and increases to
      50% if three or more lesions were identified preoperatively. Therefore, bilateral
      exploration is advocated. Lesions of the posterior lower lobes are more
      satisfactorily approached by a bilateral transverse incision and sternotomy. The
      mortality was 1% in the former and 0% in the more recent group of patients.

PMID- 1983661
TI  - [Thoracic surgery emergencies in early childhood].
AB  - Thoracic surgical emergencies in early childhood refer mainly to congenital
      malformation. To enable a successful treatment, disclosing of provable
      malformations by prenatal ultrasound screening and gradual sonographic
      diagnostics are necessary. Management of thoracic emergency situations should
      take place within an interdisciplinary team. Progress can only be expected by
      improved ultrasonographic examinations, planning of dilivery, intrapartum
      management, post partal differentiated diagnostic and therapy. As those
      prerequisits are not provided everywhere, medical care of those newborns effected
      in qualified centers is to be recommended.

PMID- 1983662
TI  - [Pneumothorax in neonates and infants].
AB  - Pneumothorax in newborns and infants can have different etiologies: alveolar
      disruption following mechanic ventilation or reanimation, surgery for congenital
      diaphragmatic hernia or esophagus atresia, staphylococcal pneumonia, or thoracic
      traumas. We studied 105 cases of pneumothorax (96 newborns) treated in our
      hospital during the last 15 years. Pleural puncture with drainage and
      antimicrobial therapy were the treatments of choice. Due to early diagnosis and
      treatment of the pneumothorax and concomitant anomalies mortality was reduced to
      17.4%.

PMID- 1983663
TI  - [Mucoviscidosis and spontaneous pneumothorax--surgical risk and treatment by
      percutaneous fibrin pleurodesis].
AB  - From 1975 to 1987, 44 of 230 patients with cystic fibrosis under our care
      underwent a total of 66 operations. There were no direct intra- or postoperative
      complications. If an optimal and aggressive adjuvant treatment is given
      postoperatively, there are no increased risks associated with surgical procedures
      in cystic fibrosis patients. Treatment of spontaneous pneumothorax remains a
      problem. An alternative treatment for pneumothorax using transcutaneous fibrin
      pleurodesis is presented.

PMID- 1983664
TI  - [Diagnosis and therapy of lung abnormalities: current status].
AB  - Malformations of the lung must be detected early before the onset of
      complications. Therefore invasive diagnostic techniques are increasingly being
      replaced by less complicated methods such as sonography, colour-coded Doppler
      sonography, DSA and CT. In certain cases, angiography and thoracoscopy should not
      be renounced. The use of these methods is preferred in combination with
      nonoperative techniques: embolisation in av-aneurysms, endoluminal endoscopic
      resection of congenital bronchial stenoses, stabilization of the bronchial wall
      in valve mechanisms or thoracoscopical resection of a cyst using fibrin glue to
      seal the area of resection. These endoscopical procedures are simplified by the
      application of laser. The smaller the child the more obvious it's advantages.

PMID- 1983665
TI  - [Breast cancer: adjuvant hormone and chemotherapy].
AB  - Indications and types of adjuvant treatment depend on the number of infiltrated
      axillary lymph nodes, menopausal and hormonal receptor status. In N0 situation is
      to date no indication for hormonal or cytotoxic therapy outside of clinical
      trials: disease-free survival may be improved but overall survival is not
      influenced. In N+ situation premenopausal patients should receive
      polychemotherapy independent from hormonal receptor status, postmenopausal
      patients with positive receptor status should be treated with tamoxifen up to 5
      years: in this situation disease-free interval and overall survival can be
      enhanced significantly.

PMID- 1983666
TI  - [Magnetic resonance tomography as a new diagnostic criterium in vascular-induced
      stenoses of the upper airways in childhood].
AB  - Magnetic resonance (MR) imaging of the trachea was performed in twenty-one
      children with congenital or acquired narrowing of the trachea or main bronchi.
      The demonstration of the trachea and the surrounding tissue and vessels on MR
      images permitted the evaluation of the cause of trachea, compression and the
      degree and location of collapse. MRI is a well-suited modality for characterizing
      tracheal narrowing without employing ionizing irradiation or intravenous contrast
      medium. In the cases presented MRI should be the diagnostic step of choice after
      tracheo-bronchoscopy. It is an enrichment of the diagnostic possibilities for
      extrinsic tracheal or bronchial stenosis in pediatric patients.

PMID- 1983667
TI  - [Chronic atelectasis--an indication for lung resection in early childhood?].
AB  - Between 1980 and 1989, 69 children underwent lung resection in our department. 45
      of them (25 boys, 20 girls, age 0-9 years) presented with atelectatic areas of
      the lung parenchyma, which had been demonstrated preoperatively in only 76%.
      Resections were performed for bronchial malformations (n = 7), sequestration (6),
      cysts (6), aspiration (1), pyocele following pulmonary artery ligation (1), upper
      lobe torsion (1), chronic pneumonia and/or bronchiectasis (14) and lobar
      emphysema with lung compression (10). The overall mortality was 4/45. Indications
      are discussed with special reference to the persistent or recurrent atelectasis.

PMID- 1983668
TI  - [Indications for surgery and results of 207 thoracotomies in children with
      diseases of the lung, pleura and mediastinum].
AB  - Between 1968 and 1988, 207 children with congenital, inflammatory, and neoplastic
      diseases of the lung, pleura, and mediastinum underwent thoracotomy. In 34
      patients indication for operation was a therapy-resistent recurrent spontaneous
      pneumothorax, in 25 benign and malignant mediastinal tumors, in 26 pulmonary
      metastases of extrathoracic primary tumors, in 42 bronchiectasis and post
      pneumonic empyema with callosity, in 21 bronchogenic and enterogenous cysts. 22
      children had benign tumors of the trachea, bronchi, and lung, 5 malignant tumors
      of the lung and chest wall. In a smaller number of children congenital defects,
      parasitic cysts, and aspergillomas as well as foreign bodies, were present. The
      surgical procedure included anatomical and atypical resections, bronchoplastic
      interventions, exstirpation of tumors and cysts, decortications and partial
      resections of the parietal pleura. There was no perioperative mortality.

PMID- 1983669
TI  - [Changes in lung function after lung resection in childhood].
AB  - 38 children and young adults were followed up 2-24 years after lung resection. A
      significant correlation between lung function studied by bodyplethysmography and
      the number of lungsegments resected was found. However, there was no correlation
      between either the age at operation, the kind of underlaying disease or the
      resected area and the postoperative lungfunction on the other hand.

PMID- 1983670
TI  - [Pediatric surgery emphasis in diseases of the mediastinum].
AB  - Airway obstruction, dysphagia and mediastinal masses are the most common causes
      for surgery of the mediastinum in the pediatric age group. From 1976-1990, 82
      children underwent such surgery: 7 tracheoplasties, 4 endotracheal resection of a
      membrane, 6 stenoses due to haemangioma or lymphangioma, 2 papillomatosis of the
      trachea, 8 pexes of the aorta or the innominate artery due to tracheomalacia, 7
      vascular rings (4 right descendent aorta, 3 double aortic arch), 4 congenital
      esophageal stenoses, 44 mediastinal tumors (20 malignant, 24 benign lesions).

PMID- 1983671
TI  - [Simplified surgical procedure for closure of the ductus arteriosus in premature
      infants].
AB  - The necessity of closing a hemodynamically significant patent ductus arteriosus
      (PDA) in a premature neonate is unequivocal. Until 12/86 the PDA was disected and
      ligated and a chest tube was inserted (127 pts.) Since 1/87 45 pts. (weight less
      than 1500 g) underwent PDA-closure using a metal-clip and no chest tube.
      Simplified surgical technique in closure of PDA in the premature neonate has led
      to a marked reduction of operating time (mean from 36 to 18 min) and has
      decreased the incidence of perioperative complications.

PMID- 1983672
TI  - [Importance of thoracic trauma in the multi-traumatized child].
AB  - The rate of thoracic trauma in multitraumatized children was assessed on the
      basis of two series of investigations: thoracic injuries increased from 8% to
      34%. Severe injury to the thorax is seen in spite of a decrease in multitraumata.
      Thoracic trauma is a central lesion with only occasional involvement of the
      peripheral extremities. To assess such injuries it is essential to pay attention
      to factors like age-related blood volume, specific fluid metabolism, different
      periods of thoracic elasticity, and the relation of lung volume to the child's
      age.

PMID- 1983673
TI  - [History of plastic surgery and its effects on our specialty].
AB  - The life and work of the first three chief surgeons at the University of Berlin
      are portrayed: Carl Ferdinand von Graefe (1787-1840), Johann Friedrich
      Dieffenbach (1792-1847) and Bernard von Langenbeck (1810-1887). Especially that
      of Dieffenbach and his time is pointed out. Similarly the founder of cosmetic
      surgery, Jaques Joseph (1865-1934), is also mentioned.

PMID- 1983674
TI  - [Malignant skin and soft tissue tumors--function preserving surgery-
      pathomorphologic aspects].
AB  - Special aspects of the localization and spontaneous regression of primaries of
      malignant melanoma, further more aspects of the pTNM-system as well as problems
      concerning perfusion therapy are pointed out and discussed. In the following the
      different biology of squamous cell and basal cell cancer dependent also on the
      localization of the primaries is described and discussed. Concerning the soft
      tissue tumor part immunohistochemical methods for the management of differential
      diagnosis are demonstrated and evaluated. These methods can be used for the
      delineation of extranodal Hodgkin and non-Hodgkin lymphoma infiltration from soft
      tissue tumors and in the differential diagnosis of polymorphous, spindle cell and
      epitheloid differentiated soft tissue tumors. Finally the problem of tumor
      grading and new grading systems (score) according to Coindre et al. are
      demonstrated and discussed.

PMID- 1983675
TI  - [Bronchial cancer--adjuvant chemotherapy].
AB  - Lung cancer patients with poor late prognosis should receive adjuvant
      chemotherapy. Its application in non-small cell lung cancer (NSCLC) is only
      justified in clinical studies, since there is no evidence of its efficacy. In
      small cell lung cancer (SCLC) chemotherapy is supplemented by local therapy
      regimens like radiotherapy and/or surgery. At present clinical studies are
      examining whether chemotherapy should be applied before or after surgical
      treatment.

PMID- 1983676
TI  - [Malignant skin and soft tissue tumors--diagnostic imaging].
AB  - Clinical evaluation of the definite size and extension of malignant skin- and
      soft tissue tumors is limited. Ultrasound provides a first orientation of tumor
      size and differentiates between solid and cystic lesions. Conventional
      Radiographs prove or rule out bone or periostial involvement and endotumoral
      calcification. If further diagnostic workup is needed MRI is the method of choice
      for defining the exact tumor topography, size and the affected compartments as
      well as the involvement of cancellous bone and bone marrow.

PMID- 1983677
TI  - [Function preserving surgery of skin and soft tissue tumors: head and neck].
AB  - Epithelial malignancies predominantly affect the head and the neck. Ablation
      requsives free margins of 1 centimeter (except in solid basal cell carcinoma). In
      a combined modality procedure resection of squamous cell carcinoma is completed
      by modified neck dissection. The majority of 397 tumor defects were treated by
      either primary suture and skin grafts or conventional flaps. Indications for 145
      microvascular operations were the failure of the classic procedure, expanded
      defects, and postoperative radiotherapy. Essential for oncological patients with
      limited life expectancy is the rapid postsurgical recovery in case of free flaps.

PMID- 1983678
TI  - [Radiotherapy of malignant soft tissue tumors].
AB  - The treatment of choice for small low-grade lesions in soft tissues may well be
      wide or radical surgical resection alone. For all other lesions (UICC stage IIa
      and larger), multimodal treatment is recommended. Pre- or postoperative
      radiotherapy reduces the local failure rate to 5%-10%. A re-resection should be
      performed after non-oncologic resections. Irradiation offers an entirely credible
      alternative to radical surgery for desmoid tumors which are not resectable.

PMID- 1983679
TI  - [Chemotherapy of skin and soft tissue tumors].
AB  - Systemic chemotherapy may be used in locally advanced or metastatic soft tissue
      sarcoma for palliation. Malignant melanoma shows objective responses in about 20%
      of patients treated with chemotherapy or with cytokines (IL-2, alpha-IFN).
      Adjuvant chemotherapy has not proven to be effective in either of these entities.
      The risk of local recurrences in limbs however can be reduced by hyperthermic
      perfusion with cytotoxic agents. Neoadjuvant (preoperative) treatment of locally
      advanced tumors needs to be prospectively evaluated. Symptomatic Kaposi sarcoma
      can be effectively treated with alpha-IFN or chemotherapy.

PMID- 1983680
TI  - [Regional deep hyperthermia of sarcoma for improving local tumor control].
AB  - 48 patients with advanced sarcomas were treated with regional hyperthermia (RHT)
      and systemic chemotherapy (ifosfamide/VP-16). 92% of the patients had been
      pretreated before entering the study. Pretreatment consisted of chemotherapy
      (33/48), surgery (9/48) or surgery plus irradiation (2/48). Following the
      conventional treatment, the patients had either relapsed (30/48) or had shown
      progressive disease (14/48) at the primary site with or without metastases. In 43
      patients the overall response rate [5 complete responders (CR) and 6 partial
      responders (PR)] was 26%, 17 patients revealed no change (NC) and 15 patients
      showed local tumor progression (PD). A significant correlation of tumor response
      (responders [CR + PR] versus non-responders [PD]) with intratumoral averaged
      temperatures could be observed.

PMID- 1983681
TI  - [Operative standards in endocrine surgery: preoperative thyroid gland diagnosis].
AB  - Even in the era of efficient methods for diagnosis of disturbances of thyroidal
      function and morphology, the diagnostic program starts with inquiry of history
      and physical examination. Today, high resolution sonography is the basic method
      for assessment of thyroidal morphology whereas scintigraphy exclusively gives
      informations on topography of function. In-vitro determinations of TSH with
      sensitive assays are the most sensitive and efficient procedures for the
      clinically most relevant question, namely the exclusion of disturbances of global
      thyroidal function.

PMID- 1983682
TI  - [Struma with euthyroidism ].
AB  - A total of 75-85% of thyroid operations are performed on euthyroid goiters; 70%
      of them are bilateral. Ultrasonography is the most important preoperatively
      examination. But even lobes classified as normal should be inspected carefully
      during operations: nodules were found in so called "normal" lobes in 22%. All
      nodules have to be resected, and attention must be paid to retrosternal and
      retrovisceral parts. Identification of recurrent nerves and parathyroid glands is
      necessary. Recurrent goiters should be prepared intercapsularly. In our own 3049
      cases of euthyroid goiters 2.4% had early recurrent nerve paralysis, 3.9%
      retrosternal and 6.6% recurrent goiters.

PMID- 1983684
TI  - [Technique of thyroid gland operation: prevention of lesions of the superior
      laryngeal nerve].
AB  - The anatomical variant of the external branch of the superior laryngeal nerve is
      at risk during thyroid surgery. We recommend a careful dissection of the upper
      thyroid pole strictly avoiding even minor mass ligatures and all vascular
      structures have to be selectively identified. Of a consecutive series of 161
      upper pole dissections the superior laryngeal nerve was found in 31% and no
      postoperative injury was detected by video stroboscopy.

PMID- 1983683
TI  - [What is the place of "selective thyroid gland resection" in surgery of benign
      nodular struma].
AB  - Remnants after "classic" Subtotal Thyroidectomy are of constant size in constant
      position. "Selective" thyroidectomy intends to remove all nodules, but to save
      normal tissue--irrespective of their localization. From July 1985 to Dec. 1989 in
      48.5% of 1124 thyroid lobes sel. surgery was performed, in 27.8% subtotal, in
      23.8% total lobectomy. Primary postop. recurrent lar. palsy occurred in 1.3%
      after sel., 1.0% after subt. and 2.7% after total lobectomy. 90% of primary
      r.l.n.p.'s were transient--after sel. lobectomy only one persistend (0.2%).
      Hypocalcemia: 0.7% after sel., 1.4% after subt. thyroidectomy. Besides better
      quality and quantity of remnants selective thyroidectomy is supported by low rate
      of complications.

PMID- 1983685
TI  - [Bronchial cancer: radiation therapy].
AB  - Postoperative radiotherapy as a routine procedure has failed to show any benefit
      in prospective randomized studies. Local failure was diminished, but survival
      rates remained unchanged, probably because of radiation complications. By
      improvement of radiation techniques, however, reduction of single doses and total
      dose and focusing postoperative irradiation of lung cancer to high risk cases
      (N2, T4) survival rates with postoperative irradiation are about 20% after 5
      years. The results of 191 treated patients are demonstrated.

PMID- 1983686
TI  - [Subtotal thyroid gland resection in immunogenic hyperthyroidism: results of a 9
      year period].
AB  - From 01. 01. 1980-31. 12. 1988 149 patients with Graves' disease were subtotally
      thyreoidectomized with little rests of 2-3 g on each side. The nervi recurrente
      and the parathyreoids were exposed. RESULTS: There was only one permanent pulsy
      of the recurrence nerve and no permanent hypoparathyreoidsm. 146 patients could
      be observed: two had a recidiv and must be treated with radiojodine. 70% of our
      patients were hypothyreotic, 20% euthyreotic. We think that the operation is the
      therapy of choice in young patients with Graves' disease.

PMID- 1983687
TI  - [Differentiated cancers].
AB  - A total of 119 papillary and 67 follicular thyroid carcinomas were subdivided
      according to the WHO classification of 1988 in the morphological subtypes of
      occult, encapsulated and invasive carcinomas. The patients were monitored over a
      followup period of 16 years postoperatively. Initially 10.6% of all patients with
      early follicular carcinoma had distant metastases and 2 of 19 died of carcinoma.
      In cases of early papillary carcinoma there were no distant metastases and no
      deaths. Limited thyroid surgery is recommended as curative surgery only for such
      patients.

PMID- 1983688
TI  - [Therapy of suspicious fine needle puncture from nodular struma with reference to
      thyroid function and morphology].
AB  - A suspicious preoperative cytology (= class "III") may be the result of various
      disorders of the thyroid presenting with cell atypia. For example hyperthyroidism
      or thyroiditis can show a cytological aspect, mimicing a differentiated
      carcinoma. Our study, comprising 231 patients with cytology "III" revealed a low
      malignancy rate (1%) in cases of concurrent hyperthyroidism or thyreoiditis. In
      contrast, 26% of the patients presenting with euthyroid nodular goiter and
      cytology "III" had a malignant histology such patients should be treated by
      primary lobectomy.

PMID- 1983689
TI  - [Primary hyperparathyroidism].
AB  - The diagnosis of primary hyperparathyroidism is based on laboratory tests showing
      high levels of calcium and parathyroid hormone. Primary hyperparathyroidism is
      treated by surgery, which is indicated in symptomatic as well as in asymptomatic
      disease, provided the latter patients are at low risk. Primary parathyroidectomy
      should be successful in at least 90% of the patients. Epidemiological studies
      show that pHPT occurs much more often than operation statistics imply. This
      situation can be improved by a more consequent differential diagnosis that
      detects up all cases of hypercalcemia.

PMID- 1983690
TI  - [Value of sono- and computerized tomography as a localization procedure in
      primary hyperparathyroidism].
AB  - A total of 56 patients underwent preoperative high-resolution sonography (4 MHz);
      33 had additional computed tomography (4 mm slices, contrast material as drip
      infusion) to localize abnormal parathyroid tissue in primary hyperparathyroidism.
      The sensitivity of sonography was 48% compared to 38% for computed tomography.
      The efficiency of both techniques was mostly dependent on size and location of
      the parathyroid. Computed tomography was superior in detecting ectopic
      parathyroids. Because of its low sensitivity sonography is only of facultative
      importance as a localization procedure for primary hyperparathyroidism. Computed
      tomography is indicated only for localizing ectopic parathyroid tissue after
      initial operation has failed.

PMID- 1983692
TI  - [Clinical management of persistent primary hyperparathyroidism].
AB  - Persistent hypercalcemia following operation for hyperparathyroidism presents a
      challenge to both the patient and the surgeon. Between 1/79 and 3/90 a total of
      351 patients with parathyroid disease were operated and 34 (10%) patients had
      persistent hyperparathyroidism. Average age was 62 years. 1/3 of pat. was
      asymptomatic and 1/3 had renal calculi. Preoperative studies were successful in
      diagnosing the affected side in 34% using CT, in 44% using sonography and in 63%
      when selective venous catheterization was used. A total of 44 operations were
      performed in 34 pat. Up to three operations were performed in 24% of patients.
      Eight of 34 pat. have refused additional surgery. Repeated surgery was successful
      in 24 pat. In eight pat. ectopic glands were identified and six of these were
      located in the mediastinum.

PMID- 1983693
TI  - [Current status of surgical therapy concepts with curative intent in esophageal
      cancer].
AB  - Curative surgical treatment of esophageal cancer involves the complete
      macroscopic and microscopic removal of the tumor (R0-resection), since this is
      the only means by which the prognosis can be improved. The treatment of choice
      for squamous cell cancer is transthoracic en bloc esophagectomy. Tumors
      penetrating the esophageal wall (T3/T4) above the tracheal bifurcation and T4
      tumors below the bifurcation should be treated preoperatively by
      (radio)chemotherapy within the framework of a multimodal therapeutic approach.

PMID- 1983691
TI  - [Coincidence of hyperparathyroidism and thyroid gland cancer].
AB  - 127 patients, operated for hyperparathyroidism in a 4-years period (1986-1989)
      were analyzed retrospectively, regarding concurrent thyroid disease. In 42
      patients (33%) thyroid resection was performed simultaneously. Of these, in five
      cases (4%), thyroid malignancy was discovered: there was one follicular
      carcinoma, one multilocular papillary tumor and three well differentiated small
      papillary carcinomas (less than 1.5 cm diameter). This prevalence of thyroid
      tumors is comparable to the results of different authors (2.5-8.5% in the
      literature). We conclude that preoperative examination should include the thyroid
      gland before parathyreotoid exploration.

PMID- 1983694
TI  - [Adrenal gland cancer].
AB  - Carcinoma of the adrenal gland is a rare type of tumor disease. Clinical
      presentation includes the same signs and symptoms as in the equivalent benign
      disease or otherwise larger palpable tumor masses. Localization is well achieved
      by ultrasound and CT-scan. 131J-MIBG-Scintican is applied selectively for adreno
      medullary tumors and 131J-nor-cholesterol for adreno-cortical tumors. For surgery
      a transabdominal or sometimes abdomino-thoracic approach is preferred.
      Sufficiently wide en-bloc resection including lymphnodes and adjacent structures
      gives hope for local radicality. The experience with 10 adrenal malignancies out
      of a total of 64 tumors (16%) is presented under various aspects.

PMID- 1983695
TI  - [Therapeutic concept in incidentaloma of the adrenal gland].
AB  - The operative approach to adrenal incidentalomas depends on the subclinical
      hormoneactivity and the risk of malignancy. In our 18 patients there were two
      pheochromocytomas (3 and 5 diameter), one with subclinical hormoneactivity and
      three malignancies, an adrenocortical carcinoma, a metastasis without primary and
      a lymphoma. The malignant tumors were larger than 5 cm. As tumors smaller than 3
      cm are usually benign they should be observed. Because of the risk of malignancy
      there is a relative indication to operate on larger tumors.

PMID- 1983696
TI  - [Insulinoma--diagnosis and therapy].
AB  - Insulin-producing tumors of the pancreas are characterised by clinical symptoms
      and the lack of correlation between serum insulin and blood glucose
      concentrations. CT and angiography are major diagnostic procedures. Surgical
      therapy prefers enucleation of the tumor together with the capsule. Today blind
      resections can be avoided.

PMID- 1983697
TI  - Isolation and characterization of 15K noncollagenous protein from bovine
      periodontal ligament.
AB  - In pursuit of the nature of noncollagenous proteins (NCP) and their biosynthesis
      in periodontal ligament (PDL), isolation, characterization and a short incubation
      study were made on the PDL of the bovine mandibular incisors. A sodium chloride
      extract from the PDL contained several noncollagenous protein components.
      Eliminating serum derived proteins by a cross-reaction with antibody against
      bovine serum proteins, a protein estimated to be 15K on 5-15% gradient NaDodSO4
      gel was the major constituent in the extract. This protein was isolated by
      sequential chromatography using Sepharose CL-6B and Sephacryl S-200 under
      dissociative conditions (4M guanidium hydrochloride). A chemical analysis of the
      protein showed that it was rich in aspartic acid, glutamic acid, glycine,
      alanine, leucine and lysine, and contained 5% sugars. Antibody directed against
      the purified PDL 15K protein reacted with the 15K protein, but no cross-reaction
      was observed with other components from the bovine PDL. A biosynthetic study of
      the protein using a short incubation with 3H-leucine indicated that the PDL cells
      produced the 15K protein and secreted it into the medium.

PMID- 1983698
TI  - [A histopathological study on hypoplasia of the enamel].
AB  - The research on the development and injury of the hard tissue of teeth was
      studied by the pedodontic departments of nine dental schools. We participated in
      this research and studied histopathologically hypoplasia of the enamel in
      particular. There were seven selected teeth which had obvious hypoplasia of the
      enamel. We conducted observations with the naked eye, replica, general
      microscopy, polarized light microscopy, fluorescence microscopy, and
      microradiography. Moreover we studied to classify these cases into three types,
      that is to say, the injury factors of whole body, locality, and unknown origin.
      The results obtained were as follows. 1) As for the injury factors for the whole
      body, the bottom of the enamel defects were located corresponding to the
      incremental line of Retzius in the case of enamel hypoplasia of the deciduous
      teeth. Also enamel hypoplasia was located near the dentino-enamel junction
      corresponding to the surface of hypoplasia. 2) As for the injury factors with
      respect to locality, the bottom of enamel defects were located corresponding to
      the incremental line of Retzius. The dentino-enamel junction was irregular and
      discontinuous, still more a part of that area, and the dentin protruded or was
      exposed. 3) As for the injury factors of unknown origin, hypoplasia was located
      from the surface of the enamel but it did not spread. Also the hypoplasia of the
      enamel did not correspond to the incremental line of Retzius. 4) Five cases had
      fluorescence lines in enamel or dentin.

PMID- 1983699
TI  - Management of insuloma patients with refractory hypoglycemia.
AB  - Insulinomas in dogs have been described frequently. The clinical signs of this
      tumor result from neuroglycopenia and increased concentrations of plasma
      catecholamines. Laboratory confirmation of hypoglycemia in association with an
      inappropriately high serum insulin concentration helps establish a tentative
      diagnosis of insulinoma. Surgical exploration of the pancreas and histologic
      evaluation is required for definitive diagnosis of insulinoma. Whenever possible,
      surgical excision of the primary lesion and associated metastases should be
      performed. The distinction between benign and malignant insulinomas is based on
      the presence or absence of metastases and clinical course of disease.
      Histologically, it is difficult to determine the malignant potential of these
      tumors. Careful medical management is essential to the dog with signs referable
      to an insulinoma, whether the patient is awaiting surgery, is not a surgical
      candidate, or has a relapse of signs after surgical resection. This chapter will
      review the clinical and diagnostic features of insulinoma in dogs and address the
      problem of refractory hypoglycemia and its management.

PMID- 1983700
TI  - Objective assessment of sleep patterns resulting from benzodiazepines prescribed
      by general practitioners.
AB  - Fifteen general practitioners treated 21 newly diagnosed insomniac patients with
      benzodiazepines. In 15 cases, a short-acting benzodiazepine was prescribed
      without regard to the type, severity, duration and probable cause of insomnia.
      Sleep-wake ambulatory recordings were made at the respective homes of the
      patients before, 1 week and 4-6 weeks after the commencement of drug treatment
      and once after stopping the medication. In spite of the large variability in
      sleep complaint as well as in prescribed drug, statistically significant changes
      of sleep-wake patterns were discerned 1 week after drug intake: sleep onset was
      shorter, light sleep (NREM stage 2) was increased and sleep efficiency was
      increased. However, although the subjective complaint appeared to have
      disappeared, these effects could no longer be measured 4 weeks later or after
      cessation of medication.

PMID- 1983701
TI  - Comparison of five anxiolytic benzodiazepines on measures of psychomotor
      performance and sleep.
AB  - The behavioural toxicity of five anxiolytic benzodiazepines was examined in 28
      volunteers who were studied in two groups of 14 subjects each. Each drug was
      taken nocte for 7 days, with a 4-week washout period between drugs. Assessments
      of psychomotor performance and sleep were made the morning following the first
      administration and the morning following the last administration. Comparisons of
      drug effect magnitudes using Cohen's d scores suggest that effects on
      psychological function should be considered as central to the selection and use
      of such compounds.

PMID- 1983702
TI  - The mosquitoes (Diptera: Culicidae) in Maliuc (Danube delta)--faunistical and
      ecological data.
AB  - The paper reports the results of the survey of the mosquito fauna in the Maliuc
      area (Danube delta) in 1983-1985. 16 mosquito species have been recorded in the
      area during the investigations: Anopheles maculipennis--complex, An. hyrcanus,
      Uranotaenia unguiculata, Coquillettidia richiardii, Culiseta annulata, Aedes
      vexans, Ae. cinereus, Ae. caspius, Ae. dorsalis, Ae. excrucians, Ae. flavescens,
      Ae. leucomelas, Ae. intrudens, Culex pipiens, C. martinii, Cx. modestus. They
      have been captured by light traps, on human bait, with entomological hand net and
      within an indoor resting site (building). Six types of habitats of adult
      mosquitoes, taking into account the characteristics of the soil and vegetation
      have been identified in the area. The quantitative and qualitative differences of
      the mosquito fauna within these six habitats have been recorded. Also, the
      suitable capture methods within every habitat have been established.

PMID- 1983704
TI  - Nucleotide sequence of rat liver tyrosine aminotransferase gene fragment.
AB  - The sequence of a 3677 nucleotide EcoRI fragment was determined that codes for
      part of the rat liver tyrosine aminotransferase gene. The sequence was compared
      with the previously determined cDNA sequence and the intron and exon boundaries
      were deduced.

PMID- 1983703
TI  - Alternatively spliced Hox-1.7 transcripts encode different protein products.
AB  - Two Hox-1.7 cDNAs, GPK5 and GPK6, were isolated from an adult guinea-pig kidney
      cDNA library by hybridization at low stringency using a Hox-1.7 cDNA probe, MH-1,
      cloned from mouse F9 teratocarcinoma cells. Sequence analysis of these two Hox
      1.7 cDNAs showed that (a) GPK5 contains a putative initiation codon preceding an
      open reading frame which includes the homeo box, and may represent the complete
      protein coding region for the corresponding Hox-1.7 transcript; (b) the amino
      acids encoded by GPK6 and MH-1 are nearly identical (with two changes); (c) both
      adult guinea-pig kidney cDNA clones share identical homeo domains with the mouse
      Hox-1.7 cDNA; and (d) both adult guinea-pig kidney cDNA clones are identical in
      the homeo box region and in the 3' untranslated region but differ significantly
      starting from the 12th codon upstream from the homeo box. These data, supported
      by Southern blot analysis, indicate that a splice site is present 5' to the homeo
      box and that alternative splicing results in transcripts encoding different
      protein products.

PMID- 1983705
TI  - [Stimulatory effects of Bacteroides gingivalis fimbriae on production of
      fibroblasts-derived thymocyte-activating factor (FTAF) by human gingival
      fibroblasts].
AB  - Bacteroides gingivalis (B. gingivalis) is isolated frequently from subgingival
      plaques of adult periodontal patients. B. gingivalis is a gram-negative anaerobic
      organism which has fimbriae on its cell surface. In the present study, B.
      gingivalis fimbriae were examined for their ability to adhere to human gingival
      fibroblasts (Gin-1), and to stimulate fibroblast-derived thymocyte-activating
      factor (FTAF) production by Gin-1 cells. The ability of the fimbriae to bind
      specifically to Gin-1 cells was clearly shown by competition assay between 125I
      labeled and unlabeled fimbriae. Significant stimulatory effect of the fimbriae on
      FTAF production was observed, when the fimbriae were added to Gin-1 cells at a
      dose of 1 microgram/ml, and this stimulation was observed as early as 24 hr after
      addition of fimbriae to the cells. It was verified by a spleen cell mitogenic
      assay for the fimbriae that the stimulatory effect was not due to
      lipopolysaccharide (LPS) contamination of the fimbriae preparation. The FTAF
      activity was inhibited about 50% by recombinant human interleukin-1 (IL-1) beta
      antiserum but not by recombinant human IL-1 alpha antiserum. Therefore, the
      present study suggests that B. gingivalis fimbriae may play a functional role in
      the pathogenesis of adult periodontal disease induced by the microorganism.

PMID- 1983707
TI  - [V Annual Reunion of the Chilean Physiological Sciences Society. XII Annual
      Reunion of the Pharmacological Society of Chile. Talca, May 3-5, 1990.
      Abstracts].

PMID- 1983706
TI  - [Studies on pyruvate kinase from pig dental pulp and brain].
AB  - Most of the enzymes involved in glycolysis are readily reversible and are also
      active in gluconeogenesis. However, three reaction steps are irreversible, i.e.,
      those catalyzed by hexokinase, phosphofructokinase, and pyruvate kinase; for in
      each of these reactions there occurs a large negative free-energy change, and
      these are reactions thus bypassed by alternate enzyme-catalyzed reactions.
      Pyruvate kinase (EC 2.7.1.40, PK) plays an important role in controlling
      glycolysis and gluconeogenesis. To clarify the characteristics of glycolysis in
      dental pulp, we examined the enzymatic properties of pyruvate kinase from pig
      dental pulp and compared them with those of the enzyme from pig brain. 1)
      Pyruvate kinase from dental pulp and brain were purified by use of ammonium
      sulphate fractionation, phosphocellulose colum chromatography, and isoelectric
      focusing. The prepared enzymes showed a single protein band on SDS polyacrylamide
      gel electrophoresis. 2) The subunit molecular weight of dental pulp and brain
      enzymes was determined to be 63,000 and 59,000, respectively. 3) Substrate
      inhibition of dental pulp and brain enzymes by phosphoenolpyruvate was not
      observed, and the relationship between reaction velocity and substrate
      concentration at pH 7.2 was explained by the Michaelis-Menten equation. Fructose
      1,6-diphosphate had no observable effect on either enzyme. 4) Effect of amino
      acids on dental pulp and brain enzyme activity were examined, and no significant
      relationship was observed between the side chain structure of amino acids and
      their potency in inhibiting dental pulp and brain enzyme activity. Glutamic and
      aspartic acids markedly inhibited dental pulp and brain enzymes at pH 7.2. 5)
      Oxalate showed inhibitory activity against dental pulp and brain enzymes, and the
      Ki value was determined to be 50 microM and 80 microM, respectively. The
      inhibition of dental pulp and brain enzyme activity by oxalate was competitive
      with respect to phosphoenolpyruvate. 6) Both dental pulp and brain enzymes were
      clearly inhibited by malate at concentrations higher than 1.0 mM: 50% and 100%
      inhibition occurred at 2.2-2.3 mM and 3.0 mM malate, respectively.

PMID- 1983708
TI  - [III Annual Reunion of the Chilean Society of Reproduction and Development.
      Santiago, 3 August 1990. Abstracts].

PMID- 1983709
TI  - [IV Annual Meeting of the Society of Cell Biology and XIV Annual Meeting of the
      Society of Biochemistry of Chile. Termas de Catillo, 30 August-1 September 1990.
      Abstracts].

PMID- 1983710
TI  - [II Congress of Biophysics of the Southern Cone. Punta de Tralca, 18-21 November
      1990. Abstracts].

PMID- 1983711
TI  - Immunomodulatory and hepatoprotective effects of in vivo treatment with free
      radical scavengers.
AB  - The hepatoprotective and immunomodulatory effects of silymarin and amino-imidazol
      carboxamid-phosphate were studied in 60 patients with compensated alcoholic
      cirrhosis of the liver in a one month double blind clinical trial. Treatment with
      both drugs normalized the elevated levels of aspartate aminotransferase, alanine
      aminotransferase and serum bilirubin, markedly reduced the high level of gamma
      glutamyl transferase, increased lectin-induced lymphoblasttransformation,
      decreased the percentage of CD8+ cells and suppressed lymphocytotoxicity. None of
      these changes occurred in the placebo-treated group. Thus the hepato-protective
      effects of silymarin and amino-imidazol-carboxamid-phosphate are accompanied by
      changes in parameters of cellular immunoreactivity of the treated patients.

PMID- 1983712
TI  - The effect of the H2-antagonist niperotidine on intragastric acidity in healthy
      subjects undergoing 24-hour pH-monitoring.
AB  - The effects of niperotidine, a novel histamine H2-receptor antagonist, on
      nocturnal gastric acid secretion in healthy volunteers, have been investigated.
      Twenty subjects were randomly assigned to the placebo (M:F = 7:3; Age 34 +/- SD3
      yrs) or to the niperotidine-treated group (M:F = 7:3; Age: 37 +/- 6 yrs) in which
      460 mg were administered at 22.00. Intragastric acidity was assessed by means of
      24-hour pH-measurement (10.00-22.00) using sensitive antimony monocrystalline
      electrodes. The percentage of daytime gastric acidity (prandial and
      interprandial) was similar in both groups (median; interquartile range): placebo
      group 87.5; 69.5-90.1 vs niperotidine 85.8; 59-89.1. Niperotidine increased the
      intragastric pH during the period 22.00-10.00. The percentage of time above pH 4
      was higher in the treated group (28.4; 14.8-50.7% vs 7.4; 1.4-10.7%; p less than
      0.02). The duration of niperotidine action was 5 to 7 hours. The nocturnal pH
      frequency curve after niperotidine was shifted toward alkaline values with a
      decrease of acidity in the pH range 1-2 (p less than 0.04). We conclude that a
      bedtime dose of niperotidine inhibits nocturnal gastric acid secretion in healthy
      subjects.

PMID- 1983713
TI  - Transcription regulating proteins and their recognition sequences.

PMID- 1983714
TI  - Histidine, histamine, and the neuroregulation of food intake: a review and
      hypothesis.
AB  - Feeding, a behavior regulated by the central nervous system (CNS), includes the
      acquisition of specific essential nutrients and the maintenance of energy
      balance. Modulation of feeding behavior is a normal part of survival, but certain
      pathological conditions interrupt or modify regulatory aspects of feeding,
      thereby leading to inappropriate intake. This review examines aspects of
      metabolism associated with the anorexia seen in animals suffering from protein
      energy malnutrition (PEM). The main focus is the indispensable amino acid
      histidine (His), the biosynthetic precursor of the neurotransmitter histamine
      (HA). In kwashiorkor-like PEM, His is elevated in plasma and brain, whereas all
      other indispensable amino acids are decreased. The elevation of His in the brain
      is to concentrations five times normal. Because the rate of HA synthesis in the
      brain is a function of the His concentration, His elevation raises the
      possibility of a profound direct effect of CNS function. In children, PEM
      consistently produces the symptoms of depressed food intake, edema, growth
      failure, and psychomotor changes. One known central effect of HA is the
      stimulation of ACTH and corticosteroid release. Based on these observations, the
      hypothesis being examined is as follows: one component of the pathophysiological
      neuroregulation of food intake involved the His-induced variation of HA
      concentration in the hypothalamus and the subsequently altered neurochemical
      activity at the corticotropin-releasing factor (CRF) neurons o the
      paraventricular nucleus (PVN).

PMID- 1983715
TI  - Evaluating total parenteral nutrition: final report and statement of the
      Technology Assessment and Practice Guidelines Forum.

PMID- 1983716
TI  - Histamine and the neuroregulation of food intake in protein malnutrition.

PMID- 1983717
TI  - Regulator genes affecting red cell antigens.
AB  - Several mechanisms may be involved to explain the action of genes that regulate
      the expression of red cell antigens. When carbohydrate antigens are involved,
      lack of an enzyme in the biochemical pathway prevents formation of the precursor
      for the next and following steps of that path, or, alternatively, addition of an
      extra sugar to the immuno-dominant sugar may produce a new structure in which the
      expression of the expected antigen is masked. Thinking of genetic rather than
      biochemical interference, a regulator gene may "switch-off" the action of a
      structural gene, and this mechanism could involve the upset of repressor and/or
      derepressor genes. The mechanisms for the regulator genes described in this
      article are unknown. The effect of XGR is limited to red cells: the expression of
      12E7 antigen on other tissues and cells, other than red cells, is invariable. The
      reported effects of XOr and XQ are for red cells, but it is unlikely that other
      cells and tissues have been studied intensively; propositi with these regulator
      genes are much rarer than people informative for XGR and In(Lu). The effects of
      In(Lu) are not limited to red cells but have been shown to regulate the
      expression of p80 on some white cells. Most of the abnormalities in Rhnull cells
      appear to be associated with the lack of the Rh antigens and lack of Rh proteins.
      The hypothesis of a functional complex involving Rh, lack of which affects
      incorporation of apparently unrelated proteins into the red cell membrane, is an
      attractive idea. Studies of the similar phenotype, Rhmod, suggest that some Rh
      specificities can be present in cells that appear to be as abnormal,
      serologically and morphologically, as Rhnull cells. Perhaps some polypeptides are
      functionally more important than others and perhaps all polypeptides required for
      the functional efficiency of the Rh complex have not yet been identified. Lack of
      Lutheran antigens is not always accompanied by modification of other red cell
      antigens. As suggested by Telen and green, if In(Lu) acts via a single mechanism,
      then that mechanism differs from that of XS2. Certainly the mechanisms of In(Lu)
      and XS2 differ in their action on the expression of CD44 or p80 antigens. The red
      cell surface is well charted territory, familiar to serologists, immunologists,
      biochemists, and geneticists. It still provides an excellent model for study of
      cell surface antigens and for the regulator genes described above that modify
      expression of some red cell antigens.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1983718
TI  - The human leukocyte antigen (HLA) system: 1990.

PMID- 1983719
TI  - Xenobiotics and cancer. Implications for chemical carcinogenesis and cancer
      chemotherapy. Proceedings of 21st International Symposium. Tokyo, 1990.

PMID- 1983720
TI  - Structure and function of P-glycoprotein in the normal liver and intestine.
AB  - Multidrug resistance (MDR) genes encode a family of membrane glycoproteins of
      approximately 170 kD (P-glycoproteins). In man and mouse, the MDR 1 (mdr 1) genes
      confer resistance to relatively hydrophobic cationic anti-cancer drugs (i.e.,
      vinblastin, adriamycin). Anti-cancer drug sensitivity is restored by addition of
      other drugs (i.e., verapamil, reserpine) which are also P-glycoprotein
      substrates. Transfection of MDR 1 genes produces the resistance phenotype and
      overexpression of P-glycoprotein. Parenchymal cells in several normal tissues
      express P-glycoprotein in the secretory domain of the plasma membrane (i.e., bile
      canaliculus of hepatocytes, brush border of proximal tubular, and small
      intestinal cells). Studies using plasma membrane vesicles of different sidedness
      derived from the bile canaliculus and small intestinal brush border permit
      characterization of P-glycoprotein as a unidirectional, temperature dependent,
      saturable, ATP-dependent transporter which is competitively inhibited by various
      anti-cancer drugs and other compounds. Transport studies using single cell
      fluorescence microscopy with image analysis confirm observations in vesicles. No
      natural substrate has been identified. Structural studies indicate that the
      requirements for substrates are molecular weight of 350 to 100, hydrophobicity,
      two planar rings, and a weak cationic charge. Alternative mechanisms of transport
      function are considered. The identity of P-glycoproteins in normal rat and human
      tissues has not been established. Antibody reactions suggest that they may belong
      to the MDR 2 or 3 class. Studies using everted gut sacs suggest that inhibition
      of P-glycoprotein may facilitate accumulation of anti-cancer drugs in the tissue.

PMID- 1983721
TI  - Multidrug resistance: a transport system of antitumor agents and xenobiotics.
AB  - Resistance of tumors to a variety of chemotherapeutic agents presents a major
      problem in cancer treatment. Resistance to such agents as doxorubicin, Vinca
      alkaloids, and actinomycin D can be acquired by tumor cells after treatment with
      a single drug. The gene responsible for multidrug resistance, termed mdr1,
      encodes a membrane glycoprotein (P-glycoprotein) that acts as a pump to transport
      various cytotoxic agents including various xenobiotics out of the cell. The
      amount of P-glycoprotein expression has been measured in tumor samples and was
      found to be elevated in intrinsically drug-resistant cancers of the colon,
      kidney, and adrenal as well as in some tumors that acquired drug resistance after
      chemotherapy. The protein was also found to be elevated in cells treated with
      xenobiotics. P-glycoprotein has been shown to bind anticancer drugs and several
      resistance-reversing agents including calcium channel blockers, and to be an
      ATPase. We recently reconstituted the purified P-glycoprotein into artificial
      liposomes. Reconstituted P-glycoprotein showed ATPase activity, ATP-dependent
      drug-transport activity, and calcium channel blocker-binding activity. This model
      provides many advantages for studies of the biochemical functions of P
      glycoprotein. In addition to these basic interests, the protein is of
      considerable interest as a target for cancer chemotherapy because it appears to
      be involved in both acquired multidrug resistance and intrinsic drug resistance
      in human cancer. The selective killing of tumor cells expressing P-glycoprotein
      could be very important in future cancer therapy.

PMID- 1983722
TI  - [Removable partial dentures applied by electric welding and soldering methods].
AB  - The joining procedure for uniting metal structures is very important in the
      dental clinic, and various kinds of metal joining methods have been performed for
      clinical application. The conventional torch soldering method using a blow torch
      has been generally adopted. However, it has several clinical problems, especially
      in the construction of removable partial dentures. The base metal wires made of a
      chromium-cobalt alloy are subject to changes in their mechanical properties
      caused by heating, when wrought wire clasps are joined to rests or frameworks. In
      addition to the flexibility of wrought wire clasps, damage to acrylic resin
      denture bases and acrylic resin teeth occurs in the repair of removable partial
      dentures. In this paper, the electric resistance welding and soldering methods
      were applied to attach wrought wire components to a removable partial denture
      framework to resolve the problems of the torch soldering method. As a result, it
      is suggested that these electric resistance welding and soldering methods have
      the following advantages, as compared with the conventional torch soldering
      method. 1. When using this electric resistance welding method, it is possible to
      fix metals temporarily to each other more securely and strongly than the
      conventional temporary fixation methods using sticky wax or acrylic resin. 2. The
      electric resistance soldering method does not require any heat insulation or a
      partition as the torch soldering method does, because the soldered area is only
      heated partially. 3. In the case of soldering electrically wrought wire clasps to
      metal structures such as rests and connectors, there is no fear of of overheating
      a wide area of wires.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1983723
TI  - [Age estimation by amino acid racemization in teeth. A comparison of data for
      aspartic acid, glutamic acid and alanine].
AB  - On the age estimation by the amino acid racemization analysis of dentin, besides
      the utilization of aspartic acid (Asp) as described in earlier reports, we
      further studied relationships between the D/L ratios based on glutamic acid (Glu)
      as well as alanine (Ala) and actual ages. The study was followed up by comparing
      racemization velocities of the three amino acids under some heating experiments.
      At four steps (6, 24, 48 and 72 hours) of hydrolysis, the coefficient values of
      D/L ratio of each amino acid and actual age were calculated as 0.986 to 0.994 for
      Asp, 0.522 to 0.806 for Glu, and 0.577 to 0.737 for Ala. The data indicate that
      Asp gives an extremely good result. Glu and Ala do provide reliable D/L ratios,
      however they are not in proportion to actual ages. Consequently, Glu and Ala seem
      to be much less suitable for utilization in age estimation. Reaction rate
      constants (k.yr-1) of racemization of Asp, Glu and Ala in antemortem teeth were
      5.3825 x 10(-4), 5.1000 x 10(-5) and 2.3875 x 10(-5), respectively. Those in
      teeth left drying at 15 degrees C were 2.4850 x 10(-8), 1.9119 x 10(-9), and
      1.11450 x 10(-9), respectively. Assuming that the reaction velocity of Asp be 1
      in both living and dry states, that of Glu were calculated as 0.09 and 0.08, that
      of Ala, 0.04 and 0.05, indicating very similar rates. The result confirmed that
      both Glu and Ala gave considerably slow racemization velocities as compared with
      Asp.

PMID- 1983724
TI  - Effectiveness of alprazolam in the treatment of chronic pain: results of a
      preliminary study.
AB  - One hundred chronic pain patients were begun on alprazolam, 1.5 mg/day. No other
      medication changes or therapeutic interventions were made. Sixteen patients were
      lost to follow-up and 1 oncology patient died. Of the 83 patients who were
      evaluated at 12 weeks, 61 (73.5%) showed improvement, and only 5 had discontinued
      the medication because of side effects. The average score of all patients had
      decreased from 3.6 to 2.2 on a verbal analog scale that rated pain severity from
      0 to 5. There was no difference in response among the various diagnostic groups
      represented in the study population.

PMID- 1983725
TI  - Sphenopalatine ganglion block: clinical use in the pain management clinic.
AB  - Clinical experience with the sphenopalatine ganglion (SPG) block combined with a
      review of prior studies led to conducting a retrospective evaluation of four
      patients with chronic pain treated with the SPG block. The review of case reports
      suggests the usefulness of SPG blocks in the pain management clinic.

PMID- 1983726
TI  - Benzodiazepine use by chronic pain patients.
AB  - Of 114 patients presenting to the Pain Management Service at the Mount Sinai
      School of Medicine with chronic pain, 38% (N = 43) were taking one or more
      benzodiazepine drugs at the time of the initial assessment. The majority of
      patients were chronic users, with 14% (N = 6) having taken the medications for 1
      2 years and 46% (N = 20) for 2 years or longer. Ninety-three percent (N = 40) of
      those given a benzodiazepine drug stated that it was initiated after the onset of
      pain. Although 86% (N = 37) were using the medication (all or in part) to improve
      sleep, they continued to report as many problems with sleep as the
      nonbenzodiazepine group did. Other drugs prescribed concurrently with the
      benzodiazepine drugs were narcotic drugs (58% of patients), antidepressant drugs
      (32%), nonsteroidal antiinflammatory agents (26%), and others (16%).
      Benzodiazepines have been reported to provide little therapeutic benefit to
      chronic pain patients, and may even exacerbate their symptoms. We have shown that
      benzodiazepine drugs are frequently prescribed for long-term use, for sleep, and
      in conjunction with narcotic drugs. Such use is contrary to generally accepted
      guidelines.

PMID- 1983727
TI  - Further studies on protein secretion by rat submandibular glands in response to
      the beta 1- and alpha 1- adrenoceptor stimuli during postnatal development.
AB  - Developmental changes in salivary proteins secreted by the submandibular glands
      of male rats from 2 to 10 weeks of age in response to the beta 1- and alpha 1
      adrenoceptor agonists, isoproterenol, methoxamine, dopamine, phenylephrine,
      epinephrine, norepinephrine and alpha-methylnoradrenaline, were studied by
      different electrophoreses and amino acid analysis. The electrophoretic patterns
      of proteins secreted by the glands in response to both stimuli changed
      dramatically every week up to 7 weeks of age, but thereafter appeared similar to
      those of adult submandibular salivary proteins. At 2 and 3 weeks of age, a few
      differences were found between the types of proteins secreted in response to two
      stimuli. These findings were also confirmed by an analysis of amino acid
      composition. The glandular levels of cGMP from 2 weeks and cAMP from 3 weeks of
      age were significantly elevated in response to methoxamine and isoproterenol. We
      conclude that functional maturation precedes morphological maturation in the
      submandibular glands of male rats.

PMID- 1983728
TI  - [Histopathological studies on tissue reactions to experimental root canal sealer
      in cats].
AB  - This study was designed to elucidate whether or not the root canal sealers, newly
      prepared here, show high affinities and promote the osteo-cicatric healing for
      the remaining dental pulp and periapical regions. For these purposes, I used two
      types of sealers, newly devised here and mainly composed of powdered corals mixed
      with propyreneglycol for the experiment 1 and powdered human dentins mixed with
      atelocollagen implant for the experiment 2. Guttapercha points with these sealers
      were applied in the premolar and molar tooth mesial or distal canals of 24 adult
      cats, whereas in controls guttapercha points with Canals, made commercially, were
      used instead of these sealers. After treatment, the periapical tissues and
      accessory root canal regions were histopathologically observed at different
      intervals throughout 30 to 130 days. The results obtained were as follows: 1.
      When guttapercha points were penetrated beyond the apical foramen and reached
      periapical tissues, prolonged inflammatory reactions of a slight or medium degree
      were observed in all three types of sealers. 2. When Canals were applied,
      prolonged inflammatory reactions were persistent if the sealer flooded out. In
      contrast, if they were in just-filling (Type-I, as termed in text), inflammatory
      reactions were often detectable at the accessory root regions. Many exudative
      inflammatory cells around the over-tip of guttapercha points were seen, as
      compared around the apicals of the dental root. 3. When powdered coral was used,
      strong inflammatory reactions was little found. Adjunction of the new bone was
      usually observed in the alveolar bone. The tendency of scar formations was seen
      in the periapical tissues where the inflammatory reaction was assumed to have
      occurred. 4. When powdered human dentin was used, in any experiments,
      inflammatory reaction were not seen with a few exceptions. However, if
      inflammatory responses were existed in a few cases, their degrees were relatively
      strong. 5. If the debris of dentin was blocked within the root canal apex, fine
      examples were seen regardless of the three types of the sealers. 6. Calcium in
      the powdered coral showed a conspicuous peak by energy X-ray analysis. The ratio
      of Ca and P of powdered human dentin was 1:1. From the above findings, both
      powdered coral and powdered human dentin could be useful as composites of
      sealers.

PMID- 1983730
TI  - General meeting of the International Organization Against Trachoma and of Ligue
      Contre le Trachome. XXVIth International Congress of Ophthalmology. Singapore,
      March 20, 1990.

PMID- 1983729
TI  - Cholinergic modulation of growth hormone-releasing hormone effects on growth
      hormone secretion in dementia.
AB  - An impairment of cholinergic and somatostatinergic neurotransmission have been
      reported in dementia. Both acetylcholine and somatostatin are involved in the
      regulation of growth hormone (GH) secretion. The effects of GH-releasing hormone
      (GHRH) 1-44 on GH release have been studied before and after the pretreatment
      with pyridostigmine or pirenzepine in subjects with senile dementia of the
      Alzheimer type, multi-infarct dementia and mixed dementia. The data have been
      compared with those obtained in an age-matched healthy control group. The GH
      response to GHRH is similar in the patients and in the controls, though the peak
      occurrence is significantly delayed in dementia. The cholinesterase inhibitor
      pyridostigmine enhances significantly the GH response to GHRH in both groups. The
      responses obtained in demented subjects are significantly larger than those found
      in the controls. Pirenzepine, a muscarinic receptor blocker, inhibits the GHRH
      effect on GH secretion in both groups. The findings may be interpreted in terms
      of an underlying impairment of the hypothalamic cholinergic neurotransmission,
      with an acetylcholine receptor supersensitivity that becomes apparent when the
      cholinergic tonus is enhanced by the inhibition of cholinesterase by
      pyridostigmine. No significant differences, due to the type of dementia, have
      been observed.

PMID- 1983731
TI  - [Study on postsoldering of Ni-Cr ceramic alloys. Effect of soldering temperature
      and atmosphere].
AB  - The effects of soldering temperatures and atmospheres on tensile strength of
      solder joints were investigated for two types of Ni-Cr ceramic alloys and one
      type of gold solder for postsoldering. Each alloy and the gold solder were
      soldered with fluoride flux in an electric furnace in three different
      temperatures and four different atmospheres. Of the three different temperatures,
      one was just over the liquidus point of the solder, another 50 degrees C higher
      than the liquidus point and the other 100 degrees C higher than the liquidus
      point. Of the four different atmospheres, one was under vacuum, another under
      vacuum with a 6 l/h argon gas flow, another under vacuum with a 12 l/h argon gas
      flow and the other under vacuum with a 24 l/h argon gas flow. Tensile strength
      testing was performed at the solder joints. The fracture surface was observed by
      EPMA. Wettability of the liquid solder on each alloy was performed by the sessile
      drop method in high-purity argon gas. The surface tension and the contact angle
      of the liquid solder on MgO were determined by the sessile drop method in high
      purity argon gas. The soldering was performed in the furnace used for the sessile
      drop method in high-purity argon gas. The results are summarized as follows. The
      tensile strength of UNI METAL-solder joints was significantly affected by the
      soldering temperature (p less than 0.01). However, the effect of the soldering
      atmosphere on the tensile strength was small. The effect of the soldering
      temperature and atmosphere on the tensile strength of Victory II-solder joints
      was small. Each alloy had a different adequate soldering temperature. With the
      increase in the soldering temperature, the diffusion layer of the solder joint
      interface increased, but no correlationship between the atmosphere and the
      diffusion layer thickness was observed. Fracture patterns of UNI METAL-solder
      joints were mixed adhesive-cohesive fractures with a large cohesive area.
      Fracture patterns of Victory II-solder joints were mixed adhesive-cohesive
      fractures with a large adhesive area. It was possible to perform the soldering
      without flux in the furnace used for the sessile drop method in a strictly
      controlled atmosphere of high-purity argon gas. Wettability of the liquid solder
      on UNI METAL was better than on Victory II. The surface tension of the solder
      used was 505.9 dyn/cm at 1000 degrees C. The contact angle of the solder used was
      163.0 degrees at 1000 degrees C.

PMID- 1983732
TI  - Characterization of colonization factor antigen CFA/I from an enterotoxigenic
      Escherichia coli strain (0128:H12).
AB  - CFA/I antigen was isolated and purified from E. coli, mutant 279 B-1-14, serotype
      0128:H12, and had the following biochemical and biological features: a) amino
      acid content was similar to that of purified antigen prepared from strain H10407;
      b) latex particles sensitization with purified CFA/I antigen produced bovine and
      human erythrocytes group A/II hemagglutination in carbohydrates presence; c)
      purified anti-CFA/I specific antibodies agglutinated CFA/I-positive
      enterotoxigenic E. coli strains; d) 3H-leucine-labelled CFA/I antigen adhered to
      rabbits intestinal mucosa at significant values; e) intestinal mucosa pretreating
      with purified CFA/I antigen, followed by 3H-leucine labelled enterotoxigenic
      bacteria infection, had a least 3 local effects: 1) intestinal mucosa protection
      against parental enterotoxigenic bacteria; 2) inhibition of CFA/I-positive
      bacteria adherence to intestinal mucosa; 3) release of approximately 96%
      intraluminally inoculated bacteria.

PMID- 1983733
TI  - Activation of a novel medullary pathway elicits a vagal, cholinergic
      bronchoconstriction in guinea-pigs.
AB  - Electrical stimulation of structures within the rostral region of the dorsal
      medulla of the guinea-pig activates a vagal cholinergic bronchoconstriction
      pathway and simultaneously activates a sympathetic inhibitory input. Removal of
      the latter by spinal section potentiated CNS-induced bronchospasm.

PMID- 1983734
TI  - Effects of isoprenaline, adrenaline and selective alpha 1- and alpha 2-
      adrenoceptor stimulation on hypoxic pulmonary vasoconstriction in rat isolated
      perfused lungs.
AB  - In the rat pulmonary vasculature perfused with blood in situ vasoconstriction
      induced by hypoxia was reversed by isoprenaline (doses greater than 1 ng) and
      adrenaline (doses greater than 30 ng) and exacerbated by phenylephrine but not UK
      14304. Doses of adrenaline less than 30 ng had no effect, except in the presence
      of propranolol (1 microM) or phentolamine (3 microM) when they caused
      vasoconstriction and vasodilation respectively, showing that, at dose levels less
      than 30 ng, adrenaline's beta- adrenoceptor vasodilator properties were balanced
      by its alpha- adrenoceptor vasoconstrictor properties. The pressor effects of
      adrenaline, in the presence of propranolol, were antagonised by prazosin (0.1
      microM) but not by equi-molar concentrations of rauwolscine. These results
      suggest that the alpha- adrenoceptor agonist property of adrenaline is of benefit
      to its use as an inhaled bronchodilator because unopposed beta- adrenoceptor
      stimulation can reverse hypoxic pulmonary vasoconstriction in poorly ventilated
      regions of the lung, promote further ventilation/perfusion mismatching and lower
      PaO2. They further suggest that adrenaline affects pulmonary vascular tone in the
      rat via alpha 1- adrenoceptors, stimulation of alpha 2- adrenoceptors having no
      effect.

PMID- 1983735
TI  - A case of criminal fraud proven by forensic dentistry.

PMID- 1983736
TI  - [Cracking in laser welds of dental Ni-Cr alloys. Effect of alloy composition].
AB  - For the purpose of clarifying the effect of alloy compositions on cracking in
      laser welds of dental Ni-Cr alloys, 12 commercial and 11 experimental Ni-Cr
      alloys for crown and bridges were subjected to pulsed YAG laser spot welding, and
      their welds were investigated by optical and scanning electron microscopy, and
      EDX and thermal analysis methods. Main conclusions are as follows. 1. Cracks in
      laser welds were solidification cracks at grain boundaries in weld fusion zones.
      2. In the case of commercial dental Ni-Cr alloys, a considerable number of
      eutectics enriched in Si, A1 and/or S were formed. Greater cracking
      susceptibility was interpreted by considering that these eutectics solidified at
      solidification temperatures far lower than the nominal solidus. 3. In the case of
      experimental Ni-Cr alloys with a small amount of eutectics, S and Si enhanced
      cracking sensitivity, but Mn reduced cracking. 4. The above results suggest that
      it is beneficial to the prevention or reduction of cracking to decrease harmful
      elements such as Si and S forming low solidification temperature eutectics or to
      add some elements such as Mn forming higher solidification temperature eutectics
      instead of lower ones.

PMID- 1983737
TI  - [A study of dental soldering. (10) The temperature distribution of infra-red
      soldering machine].
AB  - The purpose of this study is to measure the temperature distribution of focused
      energy by infra-red soldering machine. The result indicate following. 1. The
      three dimensional heating area is an ellipse shape, and soldering area is about
      10 mm in diameter centering around the focus. 2. Temperature adjustment of
      INFRARED (NEY Co.) is to use Powerlevel, and of BEAMWERDER (YOSHIDA Co.) is
      adjusting the height of the turn table. 3. When soldering with focused energy
      with infra-red machine, it is adequate to solder at the focused level or the
      upper level, after pre-heating of the soldering objects at the lower level.

PMID- 1983738
TI  - Relationship between the prevalence of antibodies to hepatitis B core antigen and
      arbovirus in fishermen from the Ribeira Valley, Brazil.
AB  - Sera from 299 fishermen 16 to 80 years old, residents in Cananeia and Iguape
      counties, southern cost of Sao Paulo State, Brazil, were studied in order to
      identify a possible association between the prevalence of specific antibodies to
      the hepatitis B virus (HBV) and exposure to haematophagus mosquitoes evaluated by
      the prevalence of arbovirus antibodies. This professional group presented the
      highest prevalence of arbovirus antibodies (54.1%) in past investigations carried
      out in this heavily forested region. Detection of antibody to hepatitis B core
      antigen (anti-HBc) in the sera was done by enzyme immunoassay (Roche). Prevalence
      of anti-HBc antibodies in this group was 31.4% (94/299) which is very high
      compared with 7.2% to 15.0% for different groups of healthy adults in State of
      Sao Paulo. No significant difference is observed between the prevalences of HBV
      antibodies in Iguape and Cananeia. Prevalence of anti-HBc and anti-arbovirus
      antibodies increases with age. There is a concordance in the distribution
      according to age groups of the frequency of anti-HBc and anti-arbovirus positive
      sera. Ag HBs was detected in 4% of the studied sera. These results support the
      hypothesis that the transmission of the hepatitis B virus and the arboviruses may
      be due to the same factor, one of the possibilities would be by anthropophilic
      mosquitoes.

PMID- 1983739
TI  - [Studies on the induction of the humoral immune responses to Bacteroides
      gingivalis fimbrial antigen in mice].
AB  - Serum and salivary antibody responses to Bacteroides gingivalis fimbriae
      administered either orally or subcutaneously (s.c.) with or without an adjuvant
      in various strains of mice were examined in this study. Following results were
      obtained. 1) Oral administration of B. gingivalis fimbriae with GM-53 as an
      adjuvant in liposomes, but not in Tris-HCl buffer, definitely enhanced the
      fimbriae-specific IgG responses, mainly IgG1 followed by IgG2b, IgG2a and IgG3 in
      serum and IgA response in saliva of BALB/c mice. On the other hand, s.c.
      injection of fimbriae with GM-53 or MDP-Lys (L18) also raised the fimbriae
      specific IgG followed by IgA and IgM responses in serum, and both IgA and IgG
      responses in saliva of BALB/c mice. Oral immunization was less effective than
      s.c. injection in terms of the production of serum antibody in the mice. However,
      the level of salivary antibody of mice injected s.c. was similar to that of mice
      immunized orally. 2) High anti-fimbriae antibodies in serum were maintained in
      BALB/c mice immunized orally with fimbriae and GM-53 in liposomes for
      approximately 7 months after the primary immunizations. Oral administration also
      induced and held the fimbriae-specific IgA response in saliva for at least 6
      months after the primary immunizations. The levels of fimbriae-specific IgA in
      saliva after the second boosters on days 123 and 124 were higher than those after
      the primary ones on days 27 and 28. 3) Among various strains of mice immunized
      orally with fimbriae and GM-53 in liposomes, BALB/c and DBA/2 mice (H-2d)
      significantly produced high levels of both serum IgG and salivary IgA antibodies
      specific for fimbriae. Furthermore, B10.D2 mice (H-2d) were responders followed
      by B10.BR (H-2k), while C57BL/10 mice (B10, H-2b) were low responders to the
      fimbriae. These results show that the combined use of fimbriae together with an
      adjuvant results in a sharply increased IgA antibody response in saliva and a
      predominantly stimulated IgG antibody in serum, and it was suggested that these
      responses are restricted by H-2 haplotype.

PMID- 1983740
TI  - [New preparations of 5 ASA].

PMID- 1983741
TI  - A double-blind controlled trial of chemoprophylaxis against tuberculosis in
      patients with silicosis in Hong Kong.

PMID- 1983742
TI  - New experimental regimens for preventive therapy of tuberculosis.

PMID- 1983743
TI  - Tuberculosis in high risk reactors.

PMID- 1983744
TI  - Isoniazid preventive therapy for low-risk tuberculin reactors.

PMID- 1983745
TI  - Isoniazid preventive therapy for low-risk adult tuberculin reactors--against.

PMID- 1983746
TI  - Preventive treatment for tuberculosis control in developing countries. The case
      for preventive chemotherapy.

PMID- 1983747
TI  - Preventive chemotherapy for tuberculosis control in developing countries. The
      case against preventive chemotherapy.

PMID- 1983748
TI  - BCG vaccination: theoretical and practical applications.

PMID- 1983749
TI  - BCG in subjects infected with HIV.

PMID- 1983750
TI  - Compliance with chemotherapy for tuberculosis. Responsibilities of the Health
      Ministry and of physicians.

PMID- 1983751
TI  - Patient compliance with preventive therapy. Operational considerations.

PMID- 1983752
TI  - Ten-year collaboration of IUATLD with national tuberculosis programmes in
      developing countries. WHO standpoint.

PMID- 1983753
TI  - Factors contributing to a successful tuberculosis control programme in Malawi.

PMID- 1983754
TI  - Case-finding and treatment results of pulmonary tuberculosis in Mozambique, 1985
      1988.

PMID- 1983755
TI  - IUATLD symposia. 1990 World Conference, Boston.

PMID- 1983756
TI  - Results of the tuberculosis control programme in Nicaragua in 1984-1989.

PMID- 1983757
TI  - The Tanzania National Tuberculosis/Leprosy Programme in the face of HIV
      infection.

PMID- 1983758
TI  - The antituberculosis programme of Benin.

PMID- 1983760
TI  - Once upon a time there was tuberculosis.

PMID- 1983759
TI  - Contemporary approaches to the serology of tuberculosis.
AB  - The current approaches in serological methods for the diagnosis of tuberculosis
      have been towards the use of M. tuberculosis-specific antigens or epitopes of
      protein antigens. Although sensitivity by using such antigens might be similar to
      that obtained by using crude or semipurified antigens, specificity was somewhat
      improved to over 95%. Among serological tools, ELISA has been the method of
      choice for detecting serum antibodies and mycobacterial antigens from clinical
      specimens because of its high sensitivity, simplicity, reproducibility and
      versatility in screening a large number of specimens. Further simple and rapid
      tests such as the agglutination test by coating various particles with purified
      or synthetic M. tuberculosis-specific antigens or antibodies will soon become
      available for field evaluation in endemic areas of tuberculosis. However, all
      these efforts can be justified only if serological tests give any meaningful
      information for the diagnosis and management of tuberculosis or for determining
      the degree of M. tuberculosis transmission in a community as a complement to the
      current tuberculin test, chest X-ray, or sputum examination. Although the
      detection of mycobacterial antigens from CSF or sputum specimens using polyclonal
      or monoclonal antibodies gave more direct evidence for M. tuberculosis infection,
      the information by the assays was not sufficient to determine whether these
      immunological tools could be used in clinical laboratories for the diagnosis of
      tuberculosis. Meanwhile, recent introduction of the very sensitive polymerase
      chain reaction (PCR) technology for the detection of M. tuberculosis DNA from
      clinical specimens (37-40) may eventually replace the immunological assays for
      the detection of mycobacterial antigens.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1983761
TI  - Prevention of tuberculosis.

PMID- 1983762
TI  - The prevalence of beta-lactamase producing bacteria in subgingival plaque and
      their sensitivity to Augmentin.
AB  - Subgingival plaque samples from 20 patients with chronic periodontitis who had
      received no antibiotics for at least 3 months were screened for the presence of
      beta-lactamase-producing bacteria. Thirteen of the patients harboured beta
      lactamase producing bacteria, most of which were members of the genus
      Bacteroides. The most frequently isolated species were Bacteroides
      melaninogenicus and Bacteroides capillosus which are often implicated in acute
      oral infections. All of the beta-lactamase-producing bacteroides strains were
      sensitive to a combination of amoxycillin with clavulanic acid (Augmentin).

PMID- 1983763
TI  - Biochemical modifications induced by Timorom in the liver carbohydrate metabolism
      of male and female rats.
AB  - A 90-day Timorom treatment of rats of both sexes modified some of the
      carbohydrate metabolism parameters. Some of the modifications were different in
      male and female rats. Glycogen storage was increased, while liver GPa activity
      was decreased in the male rats, but those modifications ran in the opposite
      direction in the female rats. In our opinion, these different reactions of male
      and female rats to Timorom (containing a nonselective beta-adrenergic blocking
      agent--timolol) depended on the different ways by which the glycogen
      phosphorylase system is activated. Many of the biochemical modifications,
      obtained after the Timorom treatment, disappeared at the end of the first post
      treatment month.

PMID- 1983764
TI  - [Early detection of medullary thyroid carcinoma in multiple endocrine neoplasia
      type II].
AB  - The early diagnosis of medullary thyroid carcinoma was made in two among six
      examined siblings belonging to two sibships that were offsprings of multiple
      endocrine neoplasia type II parents. The calcitonin secretory reserve was
      determined by a combined test using Ca++ (2 mg/kg) and pentagastrin (0.5 mcg/kg),
      intravenously. Two abnormal tests made on different days supported the diagnosis.
      Basal calcitonin levels were moderately high (90-500 pg/ml; NL = 15-85 pg/ml) and
      peak levels were also abnormal (480-1500 pg/ml; NL less than 320 pg/ml), in both
      cases. Total thyroidectomy associated to prophylactic resection of lymph nodes
      from central neck region were performed in both. A small nodule (3-5 mm) was
      found in each lobe in both cases. Pathological and immunocytochemical data
      supported the diagnosis of medullary thyroid carcinoma. C-cell hyperplasia was
      present in the peritumoral zones. Pheochromocytoma and definite
      hyperparathyroidism were not detected in these cases. Two years after surgery,
      basal and stimulated serum calcitonin levels remained normal. Carcinoembryonic
      antigen levels were and continue to be normal, in both. These seem to be the
      first cases published in this country in which this early diagnosis was made.

PMID- 1983765
TI  - [Prevention of upper digestive hemorrhage in severely ill patients].

PMID- 1983766
TI  - Design of molecules labeled with beta+ emitters for use in multitracer
      investigations using positron emission tomography.
AB  - The development of positron emission tomography (PET) in the past few years
      reflects the improvements in sensitivity and resolution of detector systems and
      the increasing access to useful positron emitting tracer molecules. Today,
      synthetic methods for routine production of compounds labeled with 15O, 13N, 11C
      and 18F with half-lives of 2, 10, 20.4 and 110 min, respectively, are available.
      This has a great impact on the use of positron emitting tracers in investigations
      in clinical studies as well as in research. In the beginning of the PET era
      studies on blood flow, blood volume and energy metabolism were the main targets
      for investigation. Today, these are only a few of the many important areas of
      PET. In the future, the main progress of PET as a general tracer method will be
      in monitoring in vivo biochemistry in normal as well as pathologic states. The
      use of multitracer investigations and multivariable statistical analysis will
      then be a most interesting approach. In this paper some aspects on this matter
      will be discussed.

PMID- 1983767
TI  - CD4+:neopterin ratio correlates with p24 antigenaemia in HIV infected patients.
AB  - In an effort to improve the Walter Reed Staging System (WR), which mainly relies
      on immune depletion parameters, by introducing viral replication and T-cell
      activation markers, we examined by p24 antigenaemia and serum neopterin levels
      (SNL) 72 HIV positive PGL, ARC and AIDS patients (11 of whom classified as WR 2,
      21 as WR 3, 16 as WR 5 and 24 as WR 6). While CD4 cell counts, already weakly
      correlating with the WR itself, did not significantly differ between p24 antigen
      (p24 AG) positive and negative patients, striking differences between the two
      groups, especially in PGL patients (p less than 0.0001), were found as far as SNL
      was concerned. In fact, SNL values, fluctuating around 10 and 30 nmol/l,
      respectively, in p24 Ag positive and negative patients regardless of their WR
      allocation, seemed rather to reflect, as global means of any given class,
      prevalence rate of p24 Ag positivity. We suggest, therefore, to use CD4/SNL ratio
      (R) for HIV infection and disease staging, as it not only may represent a
      compromise index between cellular immune depletion and T-cell activation, but
      also seems to take into account the viral replication component, already shown to
      be an important predictive marker of disease progression.

PMID- 1983768
TI  - Involvement of lymphocyte function-associated antigen-1 (LFA-1) but not ICAM-1 in
      a radioactive leukocyte cell-mediated immunity (LA-CMI) assay.
AB  - A number of monoclonal antibodies (Mab) specific to human leukocyte adherence
      molecules were investigated for their possible function in LA-CMI assay. These
      data indicate that LFA-1 appears to be directly involved in LA-CMI of human
      peripheral blood leukocytes since both MAb H52, specific to LFA-1 beta and MAb
      MHM24, specific to LA-1 alpha inhibited LA-CMI that retained distinct functional
      characteristics normally exhibited in LFA-1-dependent adhesion steps. That is,
      binding of cells onto tube wall required the presence of bivalent cations and
      metabolic energy production; it could be stimulated by phytohemagglutinin (PHA)
      and was partially dependent on intact cytoskeleton and temperature. MAbs specific
      to other adherence molecules such as ICAM-1, CD2, CD58, CD4, CD8, CD11b and LAM-1
      did not affect leukocyte adherence in this model.

PMID- 1983769
TI  - The activity of several enzymes in the urine and blood of animals in experimental
      poisoning with sublimate. Part. II. Chronic poisoning.
AB  - Fourteen guinea pigs were injected with sublimate during the period of 3 months.
      Their urine and blood was examined. In the urine an increase of activity of
      alkaline phosphatase and lactate dehydrogenase was noted. In the blood plasma an
      increase of lactate dehydrogenase activity was observed and in the blood serum
      decrease of gamma-glutamyl-transpeptidase activity. The determination of alkaline
      phosphatase in urine is a sensitive indicator of renal damage caused by mercury.
      It has a greater diagnostic value than the determination of this enzyme in the
      blood serum.

PMID- 1983770
TI  - Prokaryotic metallothionein gene characterication and expression: chromosome
      crawling by ligation-mediated PCR.

PMID- 1983771
TI  - Effect of copper deficiency and cis-diamminedichloroplatinum (II) treatment on
      the activities of renal microvillar enzymes in rats.
AB  - Recent studies have shown that some manifestations of cis
      diamminedichloroplatinum (II) (cis-Pt) induced nephrotoxicity in animals may be
      exacerbated if the animals are nutritionally deprived of copper. The objective of
      the present study was to determine the effects of cis-Pt induced toxicity on
      enzyme activities in the kidney microvilli of rats with different copper
      statuses. Weanling male rats were fed copper-deficient (CuD) (less than 1 mg/kg
      Cu of diet) or copper-adequate (CuA) (5 mg/L of Cu in drinking water) regimens.
      After 24 days, rats were given i.v. injections of either cis-Pt (5 mg/kg BW) or
      saline in a 2 x 2 factorial design. At days 2 and 4 post-injection rats were
      killed and tubular microvilli isolated from the kidney cortex. Each preparation
      was assayed for the activities of 5 membrane-bound enzymes. Angiotensin-I
      converting enzyme (ACE) activity was 20 to 30% higher in the microvilli of CuD
      rats than in controls. Cis-Pt treatment enhanced ACE activity as well, and
      activity in treated rats was 60 to 110% higher than in controls. At day 2 there
      was a 20% greater increase in ACE activity in cis-Pt-treated CuD rats than in CuA
      rats. Aminopeptidase N activity was 35% lower in CuD rats than controls, but
      activity was not affected by cis-Pt. Gamma-glutamyltransferase activity was
      lowered by as much as 30% in cis-Pt-treated rats when compared to controls, but
      there was no effect of copper deficiency. Alkaline phosphatase and neutral
      endopeptidase 24.11 activities were significantly lower in microvilli of cis-Pt
      treated rats than in those not treated.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1983772
TI  - D2 receptors in Huntington's disease: positron emission tomography findings and
      clinical correlates.
AB  - The relationship of dopamine receptor binding in the caudate nucleus and the
      putamen to neurological and neuropsychological functioning was examined in 21
      patients with Huntington's disease (HD) and eight individuals at risk of
      developing Huntington's disease. A significant reduction in relative binding of
      [11C]3-N-methylspiperone to the dopamine receptor was found in both the caudate
      and putamen of HD patients. Binding in the caudate was correlated only with tests
      of rapid coding and set alternation, while binding in the putamen was correlated
      only with duration of illness. The findings indicate that the well-described
      atrophic changes in the striatum of Huntington's disease patients are accompanied
      by receptor alterations. They also support previous animal and human studies
      indicating that the caudate nucleus plays a larger role in cognition than in
      motor functions.

PMID- 1983773
TI  - The role of excitatory amino acids in neuropsychiatric illness.
AB  - Over the past several years, research has demonstrated that the excitatory amino
      acids serve as the major excitatory neurotransmitters in cerebral cortex and
      hippocampus. Neurons that contain excitatory amino acids play crucial roles in
      neuropsychological functioning, learning, and memory. In addition, these neurons
      exert descending control over subcortical structures that is behaviorally
      antagonistic to the effects mediated by the ascending dopaminergic system.
      Disturbances of excitatory amino acid systems may contribute to the pathogenesis
      of schizophrenia and to other neuropsychiatric syndromes associated with delirium
      or dementia.

PMID- 1983774
TI  - Asymmetry in clinical features of drug-induced parkinsonism.
AB  - In clinical practice, distinguishing drug-induced parkinsonism from Parkinson's
      disease may be difficult. Asymmetry is generally not felt to be common in drug
      induced parkinsonism. The authors investigated asymmetry of signs and symptoms in
      20 patients with drug-induced parkinsonism. Tremor was identified in seven
      patients, slowness in five, and mixed symptoms in eight. A notable asymmetry of
      signs was seen in six patients. As in Parkinson's disease, subgroups seem to
      exist within the group of patients with drug-induced parkinsonism, and an
      asymmetry of signs and symptoms is not uncommon.

PMID- 1983776
TI  - Concurrent and simultaneous use of alcohol with sedatives and with tranquilizers:
      results of a national survey.
AB  - The purpose of the present study was to determine the prevalence of concurrent
      and simultaneous use of alcohol with sedatives and with tranquilizers in the
      general population and to examine differences in these rates between important
      sociodemographic subgroups. The results indicated that a sizable proportion of
      Americans engaged in both substance use practices in the year preceding the
      interview. The population estimate for simultaneous use of alcohol in combination
      with sedatives (i.e., use of both substances simultaneously or on the same
      occasion) was approximately 3 million while the concurrent use of both substances
      (i.e., during the same time period) was approximately 4 million. Corresponding
      figures for the simultaneous and concurrent use of alcohol and tranquilizers were
      both approximately 6 million. The extent of each substance use practice varied as
      a function of sociodemographic factors. Implications of these findings are
      discussed in terms of the need for age-sex-ethnic-specific prevention strategies.
      The need for future analytic epidemiological research to determine the precise
      relationship between dose, frequency, and duration of concurrent and simultaneous
      use and each adverse consequence is emphasized. The need for longitudinal
      research in the general population is also highlighted.

PMID- 1983775
TI  - Basal ganglia/limbic striatal and thalamocortical involvement in craving and loss
      of control in alcoholism.
AB  - The authors explore the possible role of basal ganglia/limbic striatal and
      thalamocortical circuits in craving and loss of control in alcohol abuse and
      dependence. Alcoholics may suffer from a defect in the neuronal systems within
      basal ganglia/limbic striatal and thalamocortical neuronal circuits, especially
      within the striatoaccumbal-ventral pallidal portion of this circuit or its
      dopaminergic nigrotegmental modulation. Alcoholic craving may result from a
      neurophysiologically driven obsession resulting from overactivity within the
      fronto-thalamic neuronal loop, and loss of control of alcohol consumption may be
      a neurophysiologically driven compulsion resulting from further impairment of the
      basal ganglia/limbic striatal portion of this circuit caused by the acute
      dopaminergic effects of intoxication.

PMID- 1983777
TI  - Differential effects of IL-2 and IL-6 on the development of three distinct
      precursor T-cell populations in the thymus.
AB  - Three distinct T-cell precursors: bone marrow cells that express low levels of
      the Thy-1 antigen but no lineage markers (Thy-1-lo/BM); CD4-, CD8-, and CD3-
      thymocytes that express low levels of the Thy-1 antigen (Thy-1-lo/Thym); and CD4
      , CD8-, and CD3- thymocytes that express high levels of the Thy-1 antigen and the
      IL-2 R alpha chain (Thy-1+/IL2R+) were isolated by fluorescence-activated cell
      sorter (FACS). These three populations expanded with different kinetics in the
      thymus of irradiated recipient mice after intrathymic transfer. When a high dose
      of human recombinant IL-2 (r-IL-2) or human recombinant IL-6 (r-IL-6) was
      administered, r-IL-6 accelerated donor Thy-1+/IL2R+ to differentiate, whereas r
      IL-2 blocked normal differentiation and expansion of donor Thy-1-lo/Thym, but did
      not show any significant effect on donor Thy-1+/IL2R+. Neither r-IL-2 nor r-IL-6
      worked directly on donor Thy-1-lo/BM in this transfer system.

PMID- 1983778
TI  - A dose-related impairment of spatial learning by the NMDA receptor antagonist, 2
      amino-5-phosphonovalerate (AP5).
AB  - This paper describes an experiment which further tested the hypothesis that
      activation of N-methyl-D-aspartate receptors plays an important role in the
      neural mechanisms underlying certain kinds of learning and memory. The results
      demonstrate that a selective N-methyl-D-aspartate receptor antagonist, D-2-amino
      5-phosphonovalerate, causes a dose-related and correlated impairment of both
      spatial learning and hippocampal long term potentiation in vivo. No dose of D-2
      amino-5-phosphonovalerate was found to block long term potentiation without
      affecting spatial learning. These data therefore support the proposed link
      between long term potentiation and certain kinds of learning, and the role of N
      methyl-D-aspartate receptors in both processes.

PMID- 1983779
TI  - EEG-brain mapping in schizophrenics with predominantly positive and negative
      symptoms. Comparative studies with remoxipride/haloperidol.
AB  - EEG brain maps obtained in 48 drug-free hospitalized schizophrenics diagnosed
      according to DSMIII demonstrated significant differences as compared with normal
      controls characterized by a decrease of alpha-1 activity, increase of beta
      activity and acceleration of the centroid. These findings suggest a state of
      sustained hyperarousal in schizophrenia. While the patients with negative
      schizophrenia showed a bi-temporal and frontal augmentation of delta/theta
      activity, patients with florid symptomatology exhibited just the opposite
      findings. Alpha-1 activity was attenuated, beta activity augmented in both groups
      with the findings more pronounced in the positive schizophrenia group. The
      increase of slow activity suggests an organic factor in the pathogenesis of the
      negative syndrome, which was supported by correlation maps between EEG measures
      and the apathy syndrome as measured by the AMDP system. Treatment of
      schizophrenics with predominantly positive symptoms with 2 different neuroleptics
      such as remoxipride and haloperidol resulted also in differential effects on
      brain activity: while haloperidol augmented delta/theta and alpha activity and
      decreased beta activity, remoxipride produced a decrease of slow and increase of
      beta activity as well as an acceleration of the centroid suggesting vigilance
      promoting properties of the drug. These differential effects on the
      neurophysiological level were also reflected at the behavioural one evaluated by
      psychometry, while global clinical evaluation showed, as expected, similar
      improvement with both drugs (apart from extrapyramidal side effects being
      significantly more pronounced after haloperidol than remoxipride). Our findings
      suggest that brain electrical signal topography is a promising method in regard
      to a better understanding of pathogenesis and treatment in schizophrenia.

PMID- 1983780
TI  - Beta 2-adrenoceptor antagonism in anxiety.
AB  - The relative role of beta 1- and beta 2-adrenoceptor antagonism in the management
      of anxiety symptoms is not clear. We studied the effect of ICI 118,551, a
      selective beta 2-antagonist, in 51 patients presenting with acute anxiety
      symptoms and fulfilling DSM-III criteria for anxiety disorder. All patients
      received placebo during the first week of treatment followed by thrice daily
      diazepam (2 mg) or ICI 118,551 (50 mg) or placebo for 4 weeks with double-blind,
      random allocation. Hamilton anxiety scale scores improved on all treatments but
      there was no significant difference between treatments. Beta 2-adrenoceptor
      antagonism does not appear to be effective in acute anxiety neurosis. Some
      earlier literature suggests that beta 1-antagonism may be more important.

PMID- 1983781
TI  - The Morbidity, Mortality and Prescription of Dialysis Symposium. Proceedings.
      Dallas, Texas, September 15-17, 1989.

PMID- 1983782
TI  - Intracellular accumulation of the cellular prion protein after mutagenesis of its
      Asn-linked glycosylation sites.
AB  - The cellular isoform of the prion protein (PrPC) is a sialoglycoprotein bound
      almost exclusively on the external surface of the plasma membrane by a glycosyl
      phosphatidylinositol anchor. The deduced amino acid sequence of Syrian hamster
      PrPC identifies two potential sites for the addition of Asn-linked carbohydrates
      at amino acids 181-183 (Asn-Ile-Thr) and 197-199 (Asn-Phe-Thr). We have altered
      these sites by replacing the threonine residues with alanine and expressed the
      mutant proteins transiently in CV1 cells utilizing a mutagenesis vector with the
      T7 promoter located upstream from the PrP gene. The T7 RNA polymerase was
      supplied by infection with a recombinant vaccinia virus. The 3 mutant proteins
      (PrPAla183, PrPAla199 and PrPAla183/199) have a reduced relative molecular weight
      compared to wild-type (wt) PrP. Deglycosylation as well as synthesis in the
      presence of tunicamycin reduced the relative molecular weight of all the PrP
      species to that of the double mutant PrPAla183/199. Our results indicate that
      both single-site mutant prion proteins are glycosylated at non-mutated sites and
      they suggest that both potential sites for Asn-linked glycosylation are utilized
      in wt PrPC. Immunofluorescence studies demonstrate that while wt PrPC localizes
      to the cell surface, all the mutant PrP molecules accumulate intracellularly. The
      site of accumulation of PrPAla183 is probably prior to the mid-Golgi stack since
      this protein does not acquire resistance to endoglycosidase H. Whether the
      intracellular locations of the mutant PrPC species are the same as those
      identified for the scrapie isoform of the prion protein (PrPSc) remains to be
      established.

PMID- 1983784
TI  - Fine force instability: a quantitative measure of neuroleptic-induced dyskinesia
      in the hand.
AB  - The results of a new procedure for the quantification of tardive dyskinesia (TD)
      in the hand are reported. Fourier analyses were made of steady-state isometric
      force control in 41 neuroleptic-treated patients with and without hand TD.
      Results indicated that spectral analysis of isometric posture represents a
      reliable, sensitive, and valid measure of neuroleptic-induced dyskinesia.

PMID- 1983783
TI  - Rat beta-galactoside alpha 2,6-sialyltransferase genomic organization: alternate
      promoters direct the synthesis of liver and kidney transcripts.
AB  - The rat beta-galactoside alpha 2,6-sialytransferase gene is differentially
      utilized by liver and kidney in the generation of mRNAs that predict
      substantially divergent polypeptides. In order to determine the biosynthetic
      relationship between these sialyltransferase mRNA isoforms, genomic sequences
      were isolated and analysed. Five exons that span at least 40 kb of DNA carry the
      coding information for the liver beta-galactoside alpha 2,6-sialyltransferase
      protein. An additional exon contains only sequences for the 5'-untranslated
      leader of the liver mRNA. In contrast, the predominant kidney mRNAs from this
      gene share only three coding exons that specify the carboxyl terminal 42% of the
      liver sialyltransferase protein sequence. In addition, these kidney mRNAs contain
      information from two other exons that comprise the 5' divergent region of these
      transcripts. Primer extension and S1 nuclease protection analysis demonstrate
      that the hepatic and kidney specific mRNAs are transcriptionally initiated at
      different sites within the sialyltransferase gene. While the hepatic
      sialyltransferase mRNAs are transcribed from the first exon, the kidney
      transcripts are initiated from a site within the third intron. Genomic regions
      upstream of both transcriptional initiation sites can regulate expression of the
      bacterial chloramphenicol acetyltransferase gene in transiently transfected L
      cells. Together, the data implicate multiple promoters as a principle mechanism
      in the generation of kidney and liver gene product diversity in sialyltransferase
      expression.

PMID- 1983785
TI  - Adjunctive fluoxetine improves global function in chronic schizophrenia.
AB  - Eight chronic schizophrenic inpatients received adjunctive fluoxetine (20 mg/day)
      for a mean of 10.6 weeks in an open clinical trial. Clinical state improved in
      all patients. Violent incidents decreased, while participation in programs and
      socialization increased.

PMID- 1983786
TI  - [XI Seminar on Amebiasis. Mexico, 6-8 December 1990].

PMID- 1983787
TI  - Emetine resistant mutants of Entamoeba histolytica overexpress mRNAs for
      multidrug resistance.
AB  - Although drug therapy is critical for control of amoebiasis, little is known
      about mechanisms of drug resistance by E. histolytica parasites. Here we tested
      the hypothesis that multidrug resistant (mdr) amoeba mutants, similar to mdr
      tumor cells, are drug resistant based upon overexpression of a P-glycoprotein
      pump that effluxes drugs from the cells. Using primers to conserved regions of
      the human P-glycoprotein and the polymerase chain reaction (PCR), we identified
      multiple 344 base par segments of amoeba DNA similar to the mammalian P
      glycoprotein. The amino acid sequences of amoeba mdr-like PCR products were from
      53 to 97 identical with each other, 55 to identical to human mdr1 sequences, and
      41-44% identical with P. falciparum mdr-like sequences. On northern blots, the
      mdr-like PCR products identified amoeba mRNAs 4.5-5 kilobases long, similar to
      the 5 kilobase mRNAs reported for the mammalian mdr gene. These mRNAs were
      increased at least seven times in emetine resistant mutant clone C2 amoebae
      versus wild-type clone A parasites. Further, the expression of the mdr-like mRNAs
      was increased three to four times when clone C2 mutants were grown under drug
      pressure versus the same parasites grown without emetine. In contrast, the number
      of genomic copies of the mdr-like DNA segments was not increased in the mutant
      clone C2 versus the wild-type clone A amoebae, and no rearrangements of the mdr
      like DNA segments by the mutant were identified on Southern blots. In conclusion
      there appears to be a family of mdr-like genes in E. histolytica, which may be
      involved in drug resistance by the parasite.

PMID- 1983788
TI  - [Effect of cysteine on protein metabolism in the liver of rats with ethanol
      induced liver damage].
AB  - Rats intoxicated with ethanol at the dose of 0.6 g/100 g of the body weight
      during 4 weeks were fed on standard diet and the one containing 0.125, 0.25 and
      0.5% L-cysteine. Intoxication of rats fed standard food causes an increase in the
      activity of cathepsin D and gamma-glutamyl-transpeptidase in the liver and an
      increase in the activity of alanine aminotransferase and gamma-glutamyl
      transpeptidase in the blood serum. Consuming by rats food containing small and
      medium quantity of cysteine causes normalization of the activity of all enzymes,
      whereas consuming food containing large quantity of cysteine does not give such
      effect.

PMID- 1983789
TI  - Prostaglandin catabolism and ulcerative colitis: effect of sulphasalazine, 5
      aminosalicylic acid and other drugs.
AB  - 1. Evidence is presented for the occurrence of type 1 prostaglandin 15
      hydroxydehydrogenase in human rectal mucosa. No evidence of the presence of type
      2 enzyme was found. 2. A 15-keto-prostaglandin reductase, responsible for the
      breakdown of 13,14-dihydro-15-keto prostaglandins to 13,14-dihydro
      prostaglandins, was also present in human rectal mucosa. 3. Ulcerative colitis
      patients catabolized prostaglandins to the same extent as the control group. PGE1
      was catabolized significantly better than PGF2 alpha. 4. 5-Aminosalicylic acid
      and sulphapyridine did not affect prostaglandin catabolism. Sulphasalazine,
      methylsulphasalazine, indomethacin, flurbiprofen, disodium cromoglycate, sodium
      salicylate and carbenoxolone sodium inhibited prostaglandin catabolism to the
      same extent in both groups. Salicylazosulphadimidine was a more potent inhibitor
      of PGE1 catabolism than of PGF2 alpha. 5. The increased prostaglandin synthesis
      reported for ulcerative colitis patients was not paralleled by increased
      catabolism, a fact possibly contributing to the accumulation of such compounds in
      the diseased state.

PMID- 1983790
TI  - Pharmacology and pain--an international view.

PMID- 1983791
TI  - Growth and development of the axr1 mutants of Arabidopsis.
AB  - We have recovered eight new auxin-resistant lines of Arabidopsis that carry
      mutations in the AXR1 gene. These eight lines, together with the 12 lines
      described in a previous report, define at least five different axr1 alleles. All
      of the mutant lines have a similar phenotype. Defects include decreases in plant
      height, root gravitropism, hypocotyl elongation, and fertility. Mutant line axr1
      3 is less resistant to auxin than the other mutant lines and has less severe
      morphological abnormalities. This correlation suggests that the morphological
      defects are a consequence of a defect in auxin action. To determine whether the
      altered morphology of mutant plants is associated with changes in cell size or
      tissue organization, tissue sections were examined using scanning electron
      microscopy. No clear differences in cell size were observed between wild-type and
      mutant tissues. However, the vascular bundles of mutant stems were found to be
      less well differentiated than those in wild-type stems. The auxin sensitivity of
      rosette-stage plants was determined by spraying plants with auxin solutions.
      Mutant rosettes were found to be significantly less sensitive to exogenously
      applied auxin than wild-type rosettes, indicating that the AXR1 gene functions in
      aerial portions of the plant. Our studies suggest that the AXR1 gene is required
      for auxin action in most, if not all, tissues of the plant and plays an important
      role in plant development. Linkage studies indicate that the gene is located on
      chromosome 1 approximately 2 centiMorgans from the closest restriction fragment
      length polymorphism.

PMID- 1983792
TI  - Function of the apetala-1 gene during Arabidopsis floral development.
AB  - We have characterized the floral phenotypes produced by the recessive homeotic
      apetala 1-1 (ap1-1) mutation in Arabidopsis. Plants homozygous for this mutation
      display a homeotic conversion of sepsis into brachts and the concomitant
      formation of floral buds in the axil of each transformed sepal. In addition,
      these flowers lack petals. We show that the loss of petal phenotype is due to the
      failure of petal primordia to be initiated. We have also constructed double
      mutant combinations with ap1 and other mutations affecting floral development.
      Based on these results, we suggest that the AP1 and the apetala 2 (AP2) genes may
      encode similar functions that are required to define the pattern of where floral
      organs arise, as well as for determinate development of the floral meristem. We
      propose that the AP1 and AP2 gene products act in concert with the product of the
      agamous (AG) locus to establish a determinate floral meristem, whereas other
      homeotic gene products are required for cells to differentiate correctly
      according to their position. These results extend the proposed role of the
      homeotic genes in floral development and suggest new models for the establishment
      of floral pattern.

PMID- 1983793
TI  - Nuclear factors interact with conserved A/T-rich elements upstream of a nodule
      enhanced glutamine synthetase gene from French bean.
AB  - The gln-gamma gene, encoding the gamma subunit of glutamine synthetase in French
      bean (Phaseolus vulgaris), is strongly induced during nodule development. We have
      determined the nucleotide sequence of a 1.3-kilobase region at its 5' end and
      have identified several sequences common to the promoter regions of late nodulin
      genes from other legume species. The 5'-flanking region was analyzed for sequence
      specific interactions with nuclear factors from French bean. A factor from
      nodules (PNF-1) was identified that binds to multiple sites between -860 and 
      154, and a related but distinct factor (PRF-1) was detected in extracts from
      uninfected roots. PNF-1 and PRF-1 bound strongly to a synthetic oligonucleotide
      containing the sequence of an A/T-rich 21-base pair imperfect repeat found at
      positions -516 and -466. The same factors also had a high affinity for a protein
      binding site from a soybean leghemoglobin gene and appeared to be closely related
      to the soybean nodule factor NAT2, which binds to A/T-rich sequences in the lbc3
      and nodulin 23 genes [Jacobsen et al. (1990). Plant Cell 2, 85-94]. Comparison of
      NAT2/PNF-1 binding sites from a variety of nodulin genes revealed the
      conservation of the short consensus core motif TATTTWAT, and evidence was
      obtained that this sequence is important for protein recognition. Cross
      recognition by PNF-1 of a protein binding site in a soybean seed protein gene
      points to the existence of a ubiquitous family of factors with related binding
      affinities. Our data suggest that PNF-1 and PRF-1 belong to an evolutionarily
      conserved group of nuclear factors that interact with specific A/T-rich sequences
      in a diverse set of plant genes. We consider the possible role of these factors
      in coregulating the expression of gln-gamma and other late nodulin genes.

PMID- 1983796
TI  - Proceedings of the 17th Collegium Internationale Neuro-Psychopharmacologium
      Congress. Kyoto, Japan, September 10-14, 1990. Abstracts.

PMID- 1983795
TI  - Purification of hamster dihydroorotate synthetase using Procion blue-Sepharose.
AB  - Dihydroorotate (DHO) synthetase is a trifunctional protein that catalyzes the
      first three reactions of de novo pyrimidine biosynthesis. A single-step procedure
      for purification of DHO synthetase from mutant hamster cells that overproduce
      this protein has been developed. The synthetase is adsorbed from a
      postmitochondrial supernatant to a column of Procion blue-Sepharose 4B and, after
      the column is washed, the synthetase is eluted as a single peak with 0.4 M KCl.
      Pooled fractions from the trailing side of this peak yield DHO synthetase with a
      specific activity for aspartate transcarbamylase of 14 mumol/min/mg protein,
      representing a purification factor of 8.5-fold and a recovery of 28% from the
      postmitochondrial supernatant. Sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis showed that the DHO synthetase was of high purity. A further 34%
      of the DHO synthetase from the leading side of the eluted peak contained a minor
      proportion of a proteolytic fragment. Similar results were obtained with an
      established four-step purification procedure.

PMID- 1983797
TI  - [Neuroendocrine neoplasms of the digestive system].

PMID- 1983794
TI  - Upstream sequences other than AAUAAA are required for efficient messenger RNA 3'
      end formation in plants.
AB  - We have characterized the upstream nucleotide sequences involved in mRNA 3'-end
      formation in the 3' regions of the cauliflower mosaic virus (CaMV) 19S/35S
      transcription unit and a pea gene encoding ribulose-1,5-bisphosphate carboxylase
      small subunit (rbcS). Sequences between 57 bases and 181 bases upstream from the
      CaMV polyadenylation site were required for efficient polyadenylation at this
      site. In addition, an AAUAAA sequence located 13 bases to 18 bases upstream from
      this site was also important for efficient mRNA 3'-end formation. An element
      located between 60 bases and 137 bases upstream from the poly(A) addition sites
      in a pea rbcS gene was needed for functioning of these sites. The CaMV -181/-57
      and rbcS -137/-60 elements were different in location and sequence composition
      from upstream sequences needed for polyadenylation in mammalian genes, but
      resembled the signals that direct mRNA 3'-end formation in yeast. However, the
      role of the AAUAAA motif in 3'-end formation in the CaMV 3' region was
      reminiscent of mRNA polyadenylation in animals. We suggest that multiple elements
      are involved in mRNA 3'-end formation in plants, and that interactions of
      different components of the plant polyadenylation apparatus with their respective
      sequence elements and with each other are needed for efficient mRNA 3'-end
      formation.

PMID- 1983799
TI  - [Present, past, and future of gastroenterology in Venezuela].

PMID- 1983798
TI  - Behaviour of different clinical, immunological and serological parameters
      observed in a group of HIV positive patients during a 12 month treatment period
      with zidovudine.
AB  - During a 12 month open clinical trial, 14 patients (6 with AIDS, 2 with ARC and 6
      with PGL) were continuously administered a daily 1200 mg dose of Zidovudine.
      Clinical course was correlated with a number of serological (HIV p24 antigen, p17
      and p24 antibodies) and immunological (CD4 cell counts, serum neopterin and beta
      2-microglobulin levels) parameters. All patients survived until the end of the
      trial: none developed major opportunistic infections, but 5 required an average
      of 7 blood transfusions each. Disappearance of p24 Ag was observed in 4 out of 7
      patients, although with a subsequent reappearance in 3; moreover, changes of p24
      Ag and HIV core Ab profiles were generally paralleled by neopterin and, to a
      lesser extent, by CD4/neopterin ratio variations. In the long run, significant
      differences between baseline and end-point results were shown by neopterin, but
      not by CD4 cell counts and beta 2-microglobulin levels. Efficacy of Zidovudine
      therapy seemed to be mainly related to clinical, but even more so, to
      immunological and serological status at baseline; in fact, severe clinical
      deterioration was observed in 2 patients who had an already low CD4/neopterin
      ratio from the beginning, coupled with a p24 Ag positivity and a negativity of
      both anti-p17 and -p24. Conversely, a stable clinical condition was observed in
      those patients in whom the reverse was true.

PMID- 1983800
TI  - Unconsciousness in flight and its prevention.
AB  - The physiological mechanism underlying two of the most potent causes of loss of
      consciousness in flight, viz. hypoxic hypoxia and exposure to rapid onset of high
      +GZ accelerations have been explored in this paper, using principally
      experimental work conducted at the Royal Air Force Institute of Aviation
      Medicine. The influence of the composition of the gas breathed before and after
      sudden decompression of the pressure cabin of an aircraft at high altitude has
      been described together with the physiological basis of the present standards for
      preventing disturbances of performance due to hypoxia following rapid
      decompression. The value and limitations of pressure breathing with oxygen at
      high pressures in preventing hypoxia on exposure to altitudes above 40,000 feet
      have been discussed together with the series of partial pressure suits used in
      the Royal Air Force. The mechanisms and occurrence of G-induced loss of
      consciousness in pilots of combat aircraft have been reviewed. The increasing
      likelihood of loss of consciousness due to G in new very agile combat aircraft is
      considered together with the limitations of the standard methods of enhancing G
      tolerance. The adoption and development of pressure breathing together with chest
      counterpressure and extended-cover G trousers which provide excellent protection
      against high levels of acceleration is described.

PMID- 1983801
TI  - A comparison of the efficacy of gastric lavage, ipecacuanha and activated
      charcoal in the emergency management of paracetamol overdose.
AB  - The aim of this prospective trial was to compare the efficacy of gastric lavage,
      activated charcoal and ipecacuanha at limiting the absorption of paracetamol in
      overdose and to assess the significance of the continued absorption of
      paracetamol following treatment. Patients aged 16 and over who had ingested 5 gms
      or more of paracetamol within 4h of admission were entered into the trial. The
      percentage fall in plasma paracetamol level was used as the measure of the
      success of a treatment at limiting absorption. The mean percentage fall was 39.3
      for gastric lavage, 52.2 for activated charcoal and 40.7 for ipecacuanha, with a
      significant difference between the treatment methods (p = 0.03). Activated
      charcoal was more effective at limiting the absorption of paracetamol following
      overdose than either gastric lavage or ipecacuanha induced emesis. In treated
      patients continuing paracetamol absorption is not significant if more than 2h
      have elapsed since ingestion.

PMID- 1983803
TI  - Aids 1990, A Year in Review. Proceedings from the 6th International Conference on
      AIDS.

PMID- 1983804
TI  - Immunology in AIDS in 1990.

PMID- 1983805
TI  - [Acute fatigue and chronic fatigue: the generic aggravated risk in the
      Carabiniere Service].

PMID- 1983802
TI  - Psychobiological evidence for the distinction between episodic and semantic
      memory.
AB  - The evidence for discrete neurobiological mechanisms that underlie episodic and
      semantic memory is reviewed. Published data from three separate lines of research
      are considered: studies of human amnesic patients, psychopharmacological studies
      of normal human subjects, and studies of working and reference memory in rodents,
      a distinction that is arguably analogous to the episodic/semantic dichotomy. It
      is concluded that the available evidence does not indicate that episodic and
      semantic memory are mediated by discrete neural subsystems. An alternative model
      of human memory is discussed, based on the concept of parallel distributed
      processing.

PMID- 1983806
TI  - [Benzodiazepines in the treatment of anxiety. The risks and alternatives].
AB  - The purpose of this article is to review the risks of pharmacological treatments
      of anxiety, mainly those due to benzodiazepines. Many mildly anxious patients do
      not need pharmacotherapy and psychological support is always an important
      component of treatment. The risks of benzodiazepine treatment increase with the
      doses used and the length of treatment, especially the risk of dependence.
      However, people who abuse benzodiazepines are a minority. Usually they also abuse
      alcohol and other drugs, probably reflecting underlying personality disorders.
      There are several alternative pharmacological treatments for anxiety. Tricyclics
      and MAO inhibitors are effective in panic disorders. Buspirone is useful in
      generalized anxiety disorder and in patients who are prone to substance abuse.
      All these alternative treatments may have disadvantages that need to be
      considered.

PMID- 1983807
TI  - 2nd European symposium on anti-nuclear and anti-cytoplasmic antibodies in
      inflammatory connective tissue diseases. Proceedings. Leuven, Belgium, May 5-27,
      1989.

PMID- 1983809
TI  - [Dermatological research to combat the harmful effects of pollution].

PMID- 1983808
TI  - [Osteomalacia and renal tubular acidosis associated with analgesic abuse. A
      clinical case].
AB  - Osteomalacia is a multifactorial bone disorder. Main causes are vitamin D
      deficiency and phosphorus depletion. Among patients with renal insufficiency the
      incidence of osteomalacia is variable and probable related to impairment of the
      synthesis of 1,25 dihydroxy-vitamin D3 (calcitriol). We report a patients with
      severe osteomalacia, hyperkalemic tubular acidosis, low serum calcitriol levels
      and insufficiency associated to a prolonged overuse of analgesic drugs.
      Differential diagnosis and pathophysiology are discussed.

PMID- 1983810
TI  - [New treatments for cryptosporidiosis].

PMID- 1983812
TI  - Determination of the optimal technique for bipolar electrocoagulation treatment.
      An experimental evaluation of the BICAP and Gold probes.
AB  - The optimal technique for use of bipolar electrocoagulation has not been
      established despite its widespread clinical use. This study of the BICAP (Circon
      ACMI, Stamford, CT) and Gold (Microvasive, Watertown, MA) probes evaluates the
      maximal force that can be applied through an endoscope and quantifies the depths
      of coagulation and sticking at varying parameters in a beef liver model. Maximal
      forces of application were determined with 3.2- and 2.3-mm probes extended 3 and
      6 cm outside the endoscope at 90 degrees and 45 degrees. Depths of coagulation
      and sticking were measured at 90 combinations of varying forces of application
      (0, 50, and 100 g), watt settings (1, 3, 5, 7, and 9), and durations (2, 6, 10,
      and 14 seconds; 3 x 2 seconds, 7 x 2 seconds) for the 3.2-mm BICAP and Gold
      probes. Mean maximal force of application decreased with greater extension or
      angulation of the probe outside the scope (3.2-mm BICAP--90 degrees: 3 cm, 110 g;
      6 cm, 56 g; 45 degrees: 3 cm, 50 g; 6 cm, 30 g; P less than 0.001; 3.2-mm Gold-
      90 degrees: 3 cm, 130 g; 6 cm, 105 g; 45 degrees: 3 cm, 62 g; 6 cm, 48 g; P less
      than 0.001). The maximal force was significantly greater with the Gold probe than
      with the BICAP in seven of eight comparisons. Significant variations among the
      mean depths of coagulation (in millimeters) for pooled data of each parameter
      were observed with force of application (BICAP: 0 g, 0.8; 50 g, 1.4; 100 g, 1.7),
      watt settings (BICAP: 1, 0.6; 3, 1.7; 5, 1.4; 7, 1.4; 9, 1.3), and duration of
      treatment (BICAP: 2 seconds, 0.8; 6 seconds, 1.1; 10 seconds, 1.4; 14 seconds,
      1.5; values for the Gold probe were comparable). The greatest depths of
      coagulation were observed at 100 g force, watt setting 3, and 14 seconds or 7 x 2
      seconds duration. Sticking paralleled depth of coagulation, increasing with force
      and duration of application. In conclusion, optimal treatment of bleeding
      gastroduodenal lesions with bipolar electrocoagulation includes (a) placing the
      tip of the endoscope en face as close as possible to the bleeding lesion, (b)
      applying the maximal force possible, (c) using a low-watt setting (approximately
      3), and (d) treating with prolonged periods of coagulation.

PMID- 1983811
TI  - Pseudomonas cepacia adherence to respiratory epithelial cells is enhanced by
      Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa and Pseudomonas cepacia are both opportunistic pathogens
      of patients with cystic fibrosis. The binding characteristics of these two
      species were compared to determine if they use similar mechanisms to adhere to
      respiratory epithelial cells. P. cepacia 249 was shown to be piliated, but there
      was no detectable homology between P. aeruginosa pilin gene probes and P. cepacia
      genomic DNA. P. cepacia and P. aeruginosa did not appear to compete for
      epithelial receptors. In the presence of purified P. aeruginosa pili, the
      adherence of 35S-labeled strain 249 to respiratory epithelial monolayers was
      unaffected, while that of P. aeruginosa PAO1 was decreased by 55%. The binding of
      P. cepacia 249 and 715j was increased by 2.4-fold and 1.5-fold, respectively, in
      the presence of an equal inoculum of PAO1. Interbacterial agglutination
      contributed to the increased adherence of P. cepacia, as the binding of 249 was
      increased twofold in the presence of irradiated PAO1. PAO1 exoproducts had a
      marked effect in enhancing the ability of the P. cepacia strains to adhere to the
      epithelial monolayers. A PAO1 supernatant increased the binding of 249 by
      eightfold and that of 715j by fourfold. Thus, there appears to be a synergistic
      relationship between P. aeruginosa and P. cepacia in which PAO1 exoproducts
      modify the epithelial cell surface, exposing receptors and facilitating increased
      P. cepacia attachment.

PMID- 1983813
TI  - Putrescine is involved in the vitamin D action in chick intestine.
AB  - We have reported that a single injection of 1 alpha,25-dihydroxyvitamin D3 into
      vitamin D-deficient chicks produces a marked increase of putrescine accumulation
      in the duodenum from two different sources, ornithine and spermidine. In the
      present study, the effects of putrescine depletion and its supplementation on
      duodenal villus length and calcium absorption were examined in newborn and 5-week
      old chicks. Administering either alpha-difluoromethylornithine, a specific
      inhibitor of ornithine decarboxylase, or N1,N4-bis(2,3-butadienyl)-1,4
      butanediamine, a specific inhibitor of polyamine oxidase, to newborn chicks
      significantly decreased the duodenal content of putrescine and calcium transport
      activity. The putrescine depletion also induced shortening of the duodenal villus
      length. The inhibition of calcium absorption and villus length in the putrescine
      depleted chicks was almost completely restored by administering putrescine to the
      birds. The effect of the putrescine depletion and its supplementation on the
      duodenal villus length and the calcium absorption was reproduced in 5-week-old
      vitamin D-deficient chicks given vitamin D3 or 1 alpha,25-dihydroxyvitamin D3.
      These results clearly indicate that putrescine is somehow involved in the vitamin
      D action in maintaining the morphological and functional development of the
      intestinal villus mucosa.

PMID- 1983814
TI  - A role for mucin in the absorption of inorganic iron and other metal cations. A
      study in rats.
AB  - The steps involved in iron absorption are poorly understood. Although transferrin
      and ferritin are water soluble, most radioiron in gut homogenates after an
      intraluminal dose of radioiron is recovered in water-insoluble precipitates. Most
      radioiron in the precipitates was insoluble in detergents and organic solvents
      and was characterized as mucins. These isolates bound iron in vitro with a Kd of
      9.09 x 10(-5). Similar iron binding was observed with commercial mucins. Iron
      binding to mucin occurred at acid pH and maintained the iron available for
      absorption with alkalinization. Similar pH-dependent binding to mucin was
      observed with zinc, cobalt, and lead. Iron competitively inhibited binding of
      these metals to mucin. However, iron chelates of ascorbate, fructose, and
      histidine donated iron to mucin at neutral pH. These data provided a role for
      gastric HCl and intestinal mucin in absorption of iron and metal cations and
      partial explanation of the competition for absorption between certain metals from
      the gut lumen. It is postulated that intestinal mucin delivers inorganic iron to
      intestinal absorptive cells in an acceptable form for absorption.

PMID- 1983815
TI  - Melanosis of the esophagus. An endoscopic, histochemical, and ultrastructural
      study.
AB  - Endoscopic, histological, and ultrastructural features of 21 cases of esophageal
      melanosis are described. These cases were detected during 1000 consecutive
      routine upper gastrointestinal endoscopies. Staining characteristics and
      ultrastructure of the pigment contained in the endoscopically visible lesions
      were found to be similar to those of true melanin.

PMID- 1983816
TI  - Geographic variation of inflammatory bowel disease within the United States.
AB  - One approach to learn about possible environmental risks in inflammatory bowel
      disease relates to studying its geographic pattern of occurrence. The geographic
      variation of inflammatory bowel disease within the United States was analyzed
      using the accumulated 17.5 million hospital discharges of all U.S. Medicare
      beneficiaries during two consecutive years. To validate the geographic pattern
      shown by the Medicare data, hospitalization was compared with mortality from
      inflammatory bowel disease among different states. Mortality and hospitalization
      statistics both suggested that the occurrence of inflammatory bowel disease was
      determined by environmental factors that had a marked geographic variation within
      the United States. Both Crohn's disease and ulcerative colitis appeared to be
      more frequent in northern parts of the United States than in southern and in
      urban more than rural parts. These trends were observed for men and women and for
      blacks and whites alike. Similar geographic patterns of Crohn's disease and
      ulcerative colitis suggested the influence of one or more identical risk factors
      for both diseases.

PMID- 1983817
TI  - Prevalence of spontaneous hepatofugal portal flow in liver cirrhosis. Clinical
      and endoscopic correlation in 228 patients.
AB  - The prevalence of spontaneous reversal of flow in the portal venous system was
      non invasively evaluated by Doppler ultrasound in 228 patients with liver
      cirrhosis and portal hypertension. Reversed flow was detected in the portal vein
      in 7 patients (3.1%), in the splenic vein in 7 patients (3.1%), and in the
      superior mesenteric vein in 5 patients (2.1%), with an overall prevalence of 8.3%
      (19/228). This prevalence did not differ in relation to the etiology of liver
      cirrhosis, whereas hepatofugal flow was found in more patients classified as
      Child's C (15.4%) and B (12.5%) than those classified as Child's A (2.7%) (P less
      than 0.02) and was associated with a higher frequency of hepatic encephalopathy
      (21% vs. 7.2%; P less than 0.05). Endoscopic evaluation of esophageal varices did
      not reveal any correlation between the presence and size of varices and
      hepatofugal flow, whereas red signs were detected more frequently in patients
      with this hemodynamic pattern (42.1% vs. 24.4%; NS). The rate of previous
      variceal bleeding was not significantly different in patients with and without
      hepatofugal flow (30.8% vs. 24.4%; NS). Conversely, the prospective evaluation of
      15 patients with hepatofugal flow and 29 matched patients with hepatopetal flow,
      derived from the group of 228 patients, followed up for a period of 12-18 months,
      showed that variceal bleeding occurred in 9 of 29 patients with hepatopetal flow
      and in none of the 15 patients with hepatofugal flow (P less than 0.02). However,
      no statistical difference was found in the survival rates. This study indicates
      that the actual prevalence of reversed flow in the portal, splenic, and superior
      mesenteric veins in a nonselected cirrhotic population is 8.3%. From a clinical
      point of view, the data suggest that this finding might be considered an
      important prognostic factor because, while occurring in cirrhotic patients with
      more severe functional impairment, it might play a protective role against the
      risk of bleeding.

PMID- 1983818
TI  - The effect of portal-systemic shunting on hepatic sex hormone receptors in male
      rats.
AB  - Signs of feminization are seen in men with cirrhosis of alcoholic but also of
      nonalcoholic origin even in the absence of markedly increased plasma estrogen
      levels. Recently identified alterations of hepatic sex hormone receptor levels
      have provided a hypothetical mechanism for the pathogenesis of the feminization
      seen in cirrhotic men. The aim of the present study was to determine the effect
      of experimental portal-systemic shunting in adult male rats on hepatic sex
      hormone receptor levels, plasma sex hormones, and two markers for sex hormone
      action in the liver. The following alterations were found in male rats with
      surgically created portacaval shunts compared with sham-operated controls: the
      hepatic content of cytosolic estrogen receptors was reduced by 35% and the
      cytosolic androgen receptors content by 59%; plasma levels of estradiol increased
      6.7-fold while those of testosterone were reduced by 71%; the estrogen-responsive
      ceruloplasmin levels were decreased by 31% and the androgen-responsive male
      specific estrogen binder by 72%. Based on these data, it can be concluded that
      portal-systemic shunting reduces the hepatic cytoplasmic content of several sex
      hormone related proteins. These changes are paralleled by a decreased estrogen
      responsiveness of the liver, as evidenced by the plasma ceruloplasmin level.

PMID- 1983819
TI  - Detection and direct sequencing of hepatitis B virus genome by DNA amplification
      method.
AB  - Hepatitis B virus (HBV) DNA was detected with amplification by the polymerase
      chain reaction method. Cloned HBV DNA equivalent to one virus genome (3 x 10(-6)
      pg) was detectable by ethidium bromide staining after 50 cycles of polymerase
      chain reaction. By applying this method, presence of HBV DNA was studied in 23
      hepatitis B surface antigen (HBsAg)-positive and 11 HBsAg-negative sera from
      patients with chronic liver disease. Hepatitis B virus DNA was positive in 8 of 8
      hepatitis B e antigen (HBeAg)-positive, in 2 of 2 HBeAg- and anti-HBe-negative,
      and in 12 of 13 anti-HBe-positive sera. Hepatitis B virus DNA was undetectable in
      all HBsAg-negative sera even with amplification. To confirm specificity, the
      amplified product was directly sequenced. Sequences around 122nd and 160th codon
      of HBs gene, which determines subtypes d/y and w/r, respectively, were analyzed.
      The results were compatible with recent reports regarding the relation between
      HBV subtypes and HBV DNA sequence at those codons. Hepatitis B virus DNA could be
      detected at the level of one virion by gene amplification method, and its
      sequence could be determined by direct sequencing in a few days.

PMID- 1983820
TI  - Reactivation of hepatitis B virus replication in patients receiving cytotoxic
      therapy. Report of a prospective study.
AB  - One hundred Chinese patients who received induction cytotoxic therapy for
      malignant lymphoma were prospectively studied to determine the incidence,
      morbidity, mortality, and predisposing factors for reactivation of hepatitis B
      virus replication during cytotoxic therapy. In 18 (67%) hepatitis B surface
      antigen-positive and 10 (14%) hepatitis B surface antigen-negative patients,
      hepatitis developed during cytotoxic therapy (P less than 0.0001). Hepatitis
      could be attributed to exacerbation or reactivation of chronic hepatitis B in 13
      (72%) hepatitis B surface antigen-positive patients but in only 2 (20%) hepatitis
      B surface antigen-negative patients (P less than 0.0001). Sudden increase or
      reactivation of hepatitis B virus replication gave rise to icteric hepatitis,
      nonfatal hepatic failure, and death in 22.3%, 3.7%, and 3.7% of patients who were
      positive for hepatitis B surface antigen; in 2%, 2%, and 0% of those positive for
      hepatitis B antibodies; and in none of those who were seronegative. Among the
      hepatitis B surface antigen-positive patients, male sex was the only factor that
      was associated with an increased risk of reactivation of hepatitis B virus
      replication. We recommend that hepatitis B surface antigen-positive patients with
      malignancies receiving cytotoxic therapy be closely monitored.

PMID- 1983821
TI  - How to protect human pancreatic enzyme activities in frozen duodenal juice.
AB  - We determined whether activity of pancreatic enzymes could be maintained in
      frozen duodenal juice by diluting the specimens or by adding nutrients or a
      chymotrypsin inhibitor. Human duodenal juice was obtained during cholecystokinin
      octapeptide IV administration. Trypsin, chymotrypsin, lipolytic, lipase, and
      colipase activities were measured in fresh undiluted or diluted (1:4 and 1:16
      with saline and T-tube bile) duodenal juice as well as after adding CaCl2,
      casein, triolein, or a chymotrypsin inhibitor. Subsequently, the samples were
      frozen at -20 degrees C, and enzyme activities were measured at 1, 2, 3, 7, 14,
      28, and 56 days. Activities of chymotrypsin and colipase did not change during
      freezer storage. Trypsin survival was variable in juice from different subjects.
      By contrast, in duodenal juice to which no nutrient or only CaCl2 had been added,
      90%, 65%, and 40% (P = 0.05 vs. undiluted) of lipolytic activity was lost by 56
      days in undiluted and 1:4 or 1:16 diluted duodenal juice samples, respectively.
      The loss of lipolytic activity was prevented (P less than 0.05) by adding casein
      or casein and triolein to undiluted and 1:4 diluted samples and turkey egg white
      to undiluted samples. The loss of lipolytic activity was strongly associated with
      loss of lipase activity (r = 0.97) but only weakly associated with loss of
      colipase activity (r = 0.49). In summary, chymotrypsin and colipase are well
      preserved in frozen duodenal juice and can be used to accurately assess
      concentrations of pancreatic enzymes after thawing frozen duodenal samples. If it
      is necessary to measure lipolytic activity after freezing samples, lipase can be
      maintained by adding casein or a chymotrypsin inhibitor to juice before freezing.

PMID- 1983822
TI  - Conjugates of ursodeoxycholate protect against cholestasis and hepatocellular
      necrosis caused by more hydrophobic bile salts. In vivo studies in the rat.
AB  - The protective effect of ursodeoxycholate conjugates against bile salt
      hepatotoxicity was studied in chronic bile fistula rats. Taurochenodeoxycholate
      or taurodeoxycholate, infused intraduodenally at 24 or 16 mumols/100 g rat per
      hour, respectively, caused cholestasis and severe hepatocellular necrosis within
      8 hours. In contrast, tauroursodeoxycholate or taurocholate at 48 mumols/100 g
      rat per hour were choleretic. Tauroursodeoxycholate was not hepatotoxic, whereas
      taurocholate produced moderate hepatocellular necrosis. Simultaneous infusion of
      tauroursodeoxycholate to rats receiving taurochenoxycholate or taurodeoxycholate
      preserved bile flow and ameliorated hepatic injury in a dose-dependent manner.
      Tauroursodeoxycholate protected equally by intravenous and intraduodenal routes.
      Intravenous glycoursodeoxycholate also was protective. The hydrophobicity index
      of infused bile salts correlated well with their toxicity. Concurrent
      administration of ursodeoxycholate conjugates did not reduce biliary recovery of
      intraduodenally infused [24-14C]-taurocholate. Biliary alkaline phosphatase
      secretion was stimulated by infusion of taurocholate, taurodeoxycholate, or
      taurochenodeoxycholate; simultaneous infusion of ursodeoxycholate conjugates
      failed to prevent this increase. We conclude that ursodeoxycholate counteracts
      hepatoxicity of more hydrophobic bile salts via a direct effect at the level of
      the liver.

PMID- 1983823
TI  - Active absorption of conjugated bile acids in vivo. Kinetic parameters and
      molecular specificity of the ileal transport system in the rat.
AB  - Active transport of conjugated bile acids by the distal ileum is required for
      efficient enterohepatic cycling of bile acids. Experiments were performed in the
      rat to obtain accurate values for Tmax and Michaelis constant (Km) of the
      absorptive area of the rat ileum and to define the structural specificity of the
      transport system. The distal fifth (20 cm) of the small intestine from an
      anesthetized animal with a biliary fistula was perfused using solutions of 10
      taurine-conjugated bile acids; a flow rate was used that was sufficiently high
      such that unstirred water layer effects were negligible and the intraluminal
      concentration remained unchanged throughout the perfused segment. The absorption
      rate was equated with the rate of hepatic bile acid secretion. Values of Tmax
      (mumol/min.kg) were markedly influenced by bile acid structure: cholyltaurine,
      12.9; ursocholyltaurine, 9.6; ursodeoxycholyl taurine, 5.0; and lagodeoxycholyl
      (3 alpha,12 beta-dihydroxy-cholanoic acid)-taurine, 1.2. Decreasing the length of
      the side chain of ursodeoxycholate conjugates from 8 to 6 carbon atoms was
      associated with a modest increase in Tmax values from 5.0 to 9.1 mumols/min.kg.
      Values of Km correlated with Tmax values and ranged from 0.5 to 5 mmol/L, being
      highest for those bile acids that were best transported. The Tmax for
      cholyltaurine transport was not reached when the intraluminal concentration was
      as high as its critical micellization concentration, precluding the definition of
      its Tmax; however, for ursocholyltaurine, with a critical micellization
      concentration of 40 mmol/L, saturation of transport was clearly shown. Kinetic
      parameters could not be obtained for two common dihydroxy conjugates
      (chenodeoxycholyltaurine and deoxycholyltaurine) because at a transport rate of 2
      mumols/min.kg systemic toxicity and death occurred. These studies define the
      maximal transport capacity of the rat ileum for taurine-conjugated bile acids;
      they indicate that the ileal transport system in the rat is of low affinity and
      high capacity for taurine conjugates of hydrophilic bile acids, and they show
      that both nuclear substituents and side chain length influence the transport rate
      of taurine-conjugated bile acids.

PMID- 1983824
TI  - Physicochemical determinants of in vitro shock-wave biliary lithotripsy.
AB  - Human gallstones were studied by visual inspection, computerized tomographic
      imaging, and chemical analysis to assess physicochemical characteristics that may
      determine the outcome of in vitro shock-wave fragmentation. Eighty-five stones
      (mean diameter: 13.2 +/- 5 mm) were each collected from different patients. Fifty
      five (65%) calculi were angular and 30 (35%) round or oval-shaped. Three easily
      obtained measures were derived from each stone's optimal computerized tomographic
      image including the mean stone density, a measure corresponding to the standard
      deviation of the mean stone density value which we termed the stone density
      distribution index and which may reflect the physicochemical heterogeneity of a
      given gallstone, as well as the density range. After the administration of 2500
      shock waves using an electrohydraulic generator, fragmentation was noted in 68
      calculi (80%) and was satisfactory in 27 (32%) (where the largest resulting
      fragment diameters were all less than or equal to 5 mm). Strong determinants of
      satisfactory fragmentation on multivariate analysis included a stone diameter of
      less than or equal to 15 mm, the presence of an angular stone shape, and a stone
      density distribution index of greater than or equal to 60 Hounsfield units. The
      other parameters did not independently determine satisfactory fragmentation.
      Prospective clinical trials are needed to assess whether these findings result in
      a better prediction of the success of extracorporeal biliary lithotripsy and a
      broadening of its indications.

PMID- 1983825
TI  - Intrahepatic cholesterol stones: a rationale for dissolution therapy.
AB  - A case of primary cholesterol hepatolithiasis is reported. Stone composition was
      documented by infrared spectroscopy, and the presence of cholesterol saturated
      bile was demonstrated using standard biochemical techniques. The patient was
      treated with operative stone extraction, choledochoscopy, biliary enteric
      anastomosis, and oral dissolution therapy. The administration of oral dissolution
      agents has altered the composition of the patient's bile and may prevent further
      stone formation. We advocate the use of both stone and biliary biochemical
      analysis for patients with primary hepatolithiasis to facilitate optimal therapy.

PMID- 1983826
TI  - Clinical application of ras gene mutation for diagnosis of pancreatic
      adenocarcinoma.
AB  - Most pancreatic adenocarcinomas are known to have ras gene (oncogene) mutations.
      The site of the mutations is localized in codon 12 of K-ras gene. Such high
      incidence and localization of the ras gene mutations have not been observed in
      any other human malignancies. Polymerase chain reaction and direct sequencing
      method enabled us to analyze DNA sequence around codon 12 of K-ras gene in small
      quantities of specimens obtained from needle biopsies and aspirate samples for
      pathological diagnosis. All the materials obtained from 12 patients with
      pancreatic adenocarcinoma showed the mutations, whereas those obtained from 6
      patients with chronic pancreatitis showed no mutations. In several cases using
      the mutations of K-ras gene as a marker, this analysis supplemented conventional
      pathology and cytology in making the diagnosis of pancreatic adenocarcinoma. The
      analysis of ras-gene mutations was useful for the clinical diagnosis of
      pancreatic adenocarcinoma.

PMID- 1983827
TI  - Herpes simplex virus hepatitis in pregnancy. Two patients successfully treated
      with acyclovir.
AB  - Two cases of herpes simplex virus hepatitis in pregnancy are presented. Each case
      was characterized by extremely high serum aminotransferase levels with minimal
      bilirubin elevation. In both cases, liver biopsy was instrumental in arriving at
      the diagnosis. In addition, computed tomography showed a radiographic appearance
      of the liver not characteristically seen in other hepatic disorders of pregnancy.
      A high index of suspicion in the second case led to early recognition and
      treatment. Despite the presence of fulminant liver failure and evidence of herpes
      encephalitis in the other case, institution of therapy with acyclovir was
      associated with complete recovery in both patients. The present cases are
      compared and contrasted with the literature. The incidence of two cases within a
      6-month period suggests that herpes simplex virus hepatitis in pregnancy may
      occur more frequently than previously reported.

PMID- 1983828
TI  - Insulin resistance in noncirrhotic idiopathic portal hypertension.
AB  - To explore further the pathogenesis of glucose intolerance and insulin resistance
      observed in patients with cirrhosis and portal hypertension, we studied a 35-year
      old woman with presinusoidal portal hypertension without cirrhosis due to nodular
      regenerative hyperplasia of the liver. After oral glucose ingestion, glucose
      tolerance remained normal; however, this occurred at the expense of a markedly
      hyperinsulinemic plasma response, suggesting the presence of insulin resistance.
      To examine this question more directly, we performed a stepwise euglycemic
      insulin clamp study in combination with an infusion of [6-3H]glucose and [1
      14C]palmitate and indirect calorimetry. The ability of insulin to promote total
      body (primarily muscle) glucose uptake was markedly impaired, whereas its effect
      to suppress hepatic glucose production was normal compared with results obtained
      in nine healthy subjects. Moreover, insulin failed to normally suppress plasma
      free fatty acid turnover and oxidation in this patient. This informative case
      demonstrates that portal hypertension alone, without hepatic dysfunction from
      cirrhosis, is associated with impaired insulin-mediated glucose and plasma free
      fatty acid metabolism and may also play a predominant role in the development of
      insulin resistance in many cirrhotic patients.

PMID- 1983829
TI  - Gastrointestinal motor dysfunction in acquired selective cholinergic dysautonomia
      associated with infectious mononucleosis.
AB  - This report documents the disturbance in gastrointestinal motor function in a
      patient with selective cholinergic dysautonomia that occurred following acute
      infectious mononucleosis. Apart from the gut, other organs affected included the
      pupils, sweat glands, lacrimal and salivary glands, and urinary bladder.
      Autonomic function tests showed the preservation of sympathetic adrenergic
      functions in contrast to the generalized involvement of postganglionic
      parasympathetic and sympathetic cholinergic nerves, including denervation
      hypersensitivity of the pupil and urinary bladder to exogenous cholinergic
      agonists. Cardiac and abdominal vagal responses were abnormal. Colon myenteric
      plexus ganglion cells were normal by morphological and immunohistochemical
      studies, suggesting that the selective cholinergic dysautonomia was the most
      likely pathophysiologic process responsible for the observed motility disorder.
      This study documents the occurrence of selective cholinergic dysautonomia
      following a viral illness, the importance of the extrinsic neural control on the
      motor function of the gastrointestinal tract, and the usefulness of combined
      motility and autonomic function testing in the evaluation of patients with
      symptoms suggestive of gut dysmotility.

PMID- 1983830
TI  - A rapid, accurate, immunohistochemical method to label proliferating cells in the
      digestive tract. A comparison with tritiated thymidine.
AB  - A rapid immunohistochemical method using 5'-bromo-2'-deoxyuridine (BrdU), a
      thymidine analog, for labeling proliferating epithelial cells was modified and
      tested for accuracy against standard tritiated thymidine autoradiography (3H-TdR)
      in rat esophagus, stomach, duodenum, and colon. Either BrdU or 3H-thymidine or
      both compounds (simultaneously) were injected IP. Histological sections of these
      tissues were immunostained with monoclonal anti-BrdU antibody, linked to
      horseradish peroxidase by standard avidin-biotin techniques and stained with
      diaminobenzidine, or sections were dipped for autoradiography, or both techniques
      were applied to the same tissue section. Results showed that (a) BrdU labeled the
      same number of proliferating cells in all organs as 3H-TdR; (b) BrdU colabeled
      with 3H-thymidine; (c) immunostaining was complete in 3-4 days but standard 3H
      TdR took 2 weeks; and (d) qualitative analysis took 50% less time with BrdU than
      with standard 3H-TdR.

PMID- 1983831
TI  - Persistent hepatitis B virus following interferon alfa therapy and liver
      transplantation.
AB  - A 44-year-old man with chronic hepatitis B virus infection and cirrhosis was
      treated with recombinant human interferon alfa for 67 days immediately before
      orthotopic liver transplantation and immunoprophylaxis with hyperimmune globulin
      to hepatitis B virus in the peritransplant period. Dot blots for hepatitis B
      virus DNA demonstrated marked reduction in viremia after 41 days of interferon
      alfa treatment. Southern analysis for hepatitis B virus in liver showed a
      pronounced decrement in actively replicating forms in the explant, although
      hepatic infection was still detectable. After liver transplantation, tests for
      serum hepatitis B virus DNA and hepatitis B surface antigen remained negative.
      The patient died 32 days after transplantation of causes unrelated to hepatitis B
      virus. DNA isolated from liver and other visceral organs at autopsy showed
      infection of the engrafted liver and the persistence of monomeric relaxed
      circular forms of hepatitis B virus DNA in pancreas, kidney, and spleen. Thus,
      graft reinfection occurred despite aggressive antiviral therapy and
      immunoprophylaxis combined with liver transplantation. Existing viral serological
      markers appear insufficiently sensitive to assess residual infectivity.

PMID- 1983832
TI  - Hepatic fibrin-ring granulomas in a patient with hepatitis A.
AB  - Hepatic fibrin-ring granulomas were found in a 30-year-old patient with
      serologically confirmed hepatitis A. Other causes associated with the presence of
      fibrin-ring granulomas in the liver, such as Hodgkin's and non-Hodgkin's
      lymphoma, cytomegalovirus infection, visceral leishmaniasis, and consumption of
      allopurinol, were ruled out. It is suggested that hepatitis A must be included in
      the differential diagnosis of a patient with hepatic fibrin-ring granulomas.

PMID- 1983833
TI  - Major histocompatibility complex class II expression on enterocytes: to present
      or not to present.

PMID- 1983834
TI  - Interferon in clinically stable, replicative chronic hepatitis B: good news for
      some.

PMID- 1983835
TI  - Crigler-Najjar syndrome type 1 explicated--thanks to liver transplantation.

PMID- 1983836
TI  - Impediments to impedance.

PMID- 1983837
TI  - Formation of unusual trihydroxy bile acids in humans: mechanism for decreasing
      hydrophobicity and toxic potential of bile acids?

PMID- 1983838
TI  - An epithelial mucin may protect the epithelium from inflammatory damage.

PMID- 1983839
TI  - Smoking habit enhanced pepsinogen group I in healthy subjects.

PMID- 1983840
TI  - Type B gastritis.

PMID- 1983841
TI  - The management of hydatid liver cysts with aspiration and alcohol.

PMID- 1983842
TI  - Transcellular transport of vitamin B12.

PMID- 1983843
TI  - Experimental hypercalcemia and pancreatic lithogenesis.

PMID- 1983844
TI  - Serum laminin and N-terminal type III procollagen in chronic alcoholic liver
      disease.

PMID- 1983845
TI  - Asymptomatic PSC--do they really have progressive diseases?

PMID- 1983846
TI  - Chronic alcohol ingestion and nutrition.

PMID- 1983847
TI  - Expression of class II molecules on intestinal epithelial cells in humans.
      Differences between normal and inflammatory bowel disease.
AB  - Expression of class II antigens on human intestinal epithelial cells was assessed
      using a sensitive avidinbiotin-peroxidase technique. HLA-DR was present
      predominantly in the normal small bowel with diminished but evident expression in
      the colon. HLA-DP staining was less prominent, and HLA-DQ was absent. In
      inflammatory bowel disease the expression of both HLA-DR and HLA-DP was
      increased, but that for HLA-DQ remained absent, suggesting an inherent defect in
      the ability of intestinal epithelial cells to express HLA-DQ. In related
      experiments, an interferon gamma-treated malignant epithelial cell line T84 also
      failed to stain for HLA-DQ and HLA-DP despite the presence of HLA-DR. Isolated
      RNAs for all three subclasses of HLA-D were detectable by slot-blot analysis,
      suggesting that the lack of HLA-DQ expression relates to posttranscriptional
      defects in intestinal epithelium. These and other differences with conventional
      class II antigen-positive accessory cells (macrophages/B cells) may help to
      explain the unique properties of intestinal epithelial cells as antigen
      presenting cells.

PMID- 1983848
TI  - Injection or heat probe for bleeding ulcer.
AB  - A prospective randomized trial was performed to compare the efficacy of
      endoscopic epinephrine injection and heat probe treatment in actively bleeding
      peptic ulcers. Emergency endoscopy in 1758 patients over an 18-month period
      identified 132 patients with active ulcer bleeding. They were randomized to
      receive either endoscopic epinephrine injection or heat probe treatment. After
      endoscopy, the patients were transferred to the surgical gastroenterology ward
      and were managed by surgeons unaware of the treatment option. Bleeding was
      initially controlled in 96% by epinephrine injection and in 83% by heat probe (P
      less than 0.05). There was no significant difference in outcome as measured by
      transfusion requirement (4.5 units vs. 3.8 units), emergency surgery (20% vs.
      22%), hospital stay (8 days vs. 7 days), and mortality (2 vs. 4) between the
      injection group and the heat probe group. Two patients in the heat probe group
      experienced perforation. We conclude that both endoscopic epinephrine injection
      and heat probe treatment are effective in stopping bleeding from actively
      bleeding ulcers. Epinephrine injection is technically easier to perform and has a
      higher initial success rate.

PMID- 1983849
TI  - Exogenous surface-active phospholipid protects Necturus gastric mucosa against
      luminal acid and barrier-breaking agents.
AB  - The nature of the protective action of exogenous surface-active phospholipid on
      gastric mucosa was studied in isolated Necturus antral mucosa by measuring
      intracellular pH and intraepithelial potentials and resistances with a
      microelectrode technique. Exposure of the antral mucosa to luminal pH 2 acidified
      intracellular pH in surface epithelial cells by 0.6-0.3 pH units. A 20-minute
      pretreatment with exogenous (pulmonary) surfactanlike phospholipid completely
      abolished this effect. Obviously, phospholipid protected the mucosa against
      intracellular acidosis by decreasing the apical cell membrane conductance to H+
      (and other ions), because it increased apical cell membrane resistance by +108%
      and total transcellular resistance by +86% but had no significant effects on
      paracellular or total transepithelial resistances. In mucosas exposed to three
      barrier-breaking agents, 10 mmol/L acetylsalicylic acid, 20% (vol/vol) ethanol,
      and 10 mmol/L taurocholate, at acid luminal perfusate (pH 2.0-2.5), a profound
      intracellular acidification of 0.9-1.3 pH units/15 min occurred. Pretreatment of
      the tissue with phospholipid significantly opposed intracellular acidification,
      but the modulatory influences on the changes in intraepithelial potentials or
      resistances were less conspicuous and mostly insignificant.

PMID- 1983850
TI  - Airway responsiveness to inhaled methacholine in patients with irritable bowel
      syndrome.
AB  - We examined whether patients with irritable bowel syndrome have increased airway
      responsiveness by measuring forced expiratory volumes in 1 second (FEV1) after
      inhalation of increasing concentrations of methacholine. Responses obtained in 11
      IBS patients were compared with those obtained in 11 normal subjects and in 11
      subjects with organic disease of the gut or its related organs. All subjects were
      selected so that other factors that might contribute to increased airway
      responsiveness were excluded. The methacholine concentration that caused a 20%
      fall in the FEV1 (PC20), as well as the reduction in FEV1 induced by each
      methacholine concentration, were used to assess airway responsiveness. The
      geometric mean PC20 was 197.6 mg/mL (%SEM, 1.15) for normal subjects, 83.9 mg/mL
      (%SEM, 1.51) for subjects with organic bowel disease (P = 0.012), and only 12.8
      mg/mL (%SEM, 1.74) for IBS patients (P less than 0.0001). The 22.5% +/- 2.5%
      decrease in FEV1 induced by 64 mg/mL of methacholine in IBS patients was
      significantly greater than that of 12.3% +/- 1.5% observed in healthy subjects (P
      = 0.003). In contrast, the 15.7% +/- 2.0% decrease in FEV1 observed in patients
      with organic disease was not different from that seen in normal subjects (P =
      0.189). We conclude that IBS is associated with increased airway responsiveness
      following challenge with methacholine.

PMID- 1983851
TI  - Anatomic contribution to differences in rabbit colonic muscle contraction.
AB  - The aim of this study was to determine if differences in the force of contraction
      in different regions of the rabbit colon are associated with variations in the
      histology of the corresponding muscle tissues. Circular and longitudinal muscles
      were isolated from strips of proximal and distal colonic muscle. Muscle strips
      stretched to L0 were either stimulated to contract or were processed for electron
      microscopy. Cross-sections of the smooth muscle cells of the taenia coli had a
      larger perimeter (P less than 0.001) and were surrounded by increased
      extracellular matrix (28% of the standardized box) compared with the muscle cells
      from the other sites in the colon (7%-13%) (P less than 0.001). Cross-sections of
      the proximal circular muscle cells had a smaller perimeter and were present in a
      greater number than the cells from other areas of the colon. The distal circular
      muscle generated a larger force than the other muscles after stimulation with
      bethanechol or K+ (P less than 0.05). The taenia developed less force than the
      other muscles (P less than 0.05). Bethanechol was a less potent stimulant for the
      longitudinal muscles than for the circular muscles (P less than 0.05). This study
      suggests that (1) the decreased efficacy of bethanechol and K+ stimulation of the
      taenia coli is caused in part by the smaller number of cells that are available
      to contract and (2) the increased efficacy for the stimulation of the distal
      circular muscle compared with the proximal circular muscle is unrelated to the
      mass of muscle and seems to be related to an inherent property of the muscle.

PMID- 1983852
TI  - Transport of riboflavin in human intestinal brush border membrane vesicles.
AB  - The transport of riboflavin across the brush border membrane of human intestine
      was examined using the established brush border membrane vesicle technique. Both
      osmolarity and temperature studies have concluded that the uptake of riboflavin
      by these vesicles is mostly the result of transport of riboflavin into an active
      intravesicular space with less binding to membrane surfaces. When an inwardly
      directed Na+ gradient was imposed, transport of riboflavin was linear with time
      for approximately 20 seconds of incubation and was significantly higher than in
      the presence of an identical K+ gradient. Initial rate of transport of riboflavin
      as a function of concentration was found to include a saturable component in the
      presence of an inwardly directed Na+ gradient but was linear in the presence of
      an identical K+ gradient. The apparent Km and Vmax of the Na+ stimulated
      transport process were found to be 7.26 mumols/L and 0.97 pmol/mg protein per 10
      seconds, respectively. The addition of high concentrations of unlabeled
      riboflavin and its structural analogue lumiflavin to the incubation medium caused
      significant inhibition in the transport of 3H-riboflavin in the brush border
      membrane vesicle incubated in the presence of an inwardly directed Na+ gradient
      but not in vesicles incubated in the presence of an identical K+ gradient.
      Inducing a relatively positive intravesicular space with the use of valinomycin
      and an inwardly directed K+ gradient caused significant inhibition in the
      transport of riboflavin. On the other hand, inducing a relatively negative
      intravesicular space with the use of anions of different lipid permeabilities
      caused significant stimulation in the transport of riboflavin. These results
      demonstrate that riboflavin transport in human intestinal brush border membrane
      vesicle is through a carrier-mediated system. This system functions in the
      presence of a Na(+)-gradient and seems to transport the substrate by an
      electrogenic process.

PMID- 1983853
TI  - Human intestine matures as nude mouse xenograft.
AB  - This report describes a novel system for the study of the development and
      function of human intestine. Human fetal bowel transplanted into a subcutaneous
      tunnel on the back of athymic nude (nu/nu) mice develops a new microcirculation
      within 4 weeks. Tissues undergo morphological development, become similar to
      adult human bowel tissue, and may survive for 6 months after transplantation.
      Monoclonal antibody immunoperoxidase staining shows that the epithelial and some
      endothelial elements are of human phenotype, but the circulating blood cells and
      migrating mucosal lymphocytes are of mouse origin.

PMID- 1983855
TI  - Long term survivors of childhood cancer.

PMID- 1983854
TI  - Plasma vasoactive intestinal polypeptide concentration determination in patients
      with diarrhea.
AB  - Determination of plasma levels of vasoactive intestinal polypeptide (VIP) has
      been used for screening patients with chronic diarrhea to identify potential
      neuroendocrine tumors. This 6-year blinded study from 1981 to 1986 examines the
      causes of elevated VIP levels in patients. In healthy volunteers ( n = 144), VIP
      concentrations ranged from 14 to 76 pg/mL (mean +/- SE, 28 +/- 12), whereas in
      chronic renal failure, 4 of 34 patients or 12% [serum creatinine 4.5 - 9.0 mg/dL
      (397-795 mumols/L)] had an elevation to greater than 100 pg/mL. No patient with
      idiopathic hepatic cirrhosis (n = 12) had elevation of serum concentration of
      this peptide. Among 588 consecutive unselected patients undergoing evaluation for
      chronic diarrhea (n = 362; 62%) or possible neuroendocrine tumor (n = 214; 36%),
      23 patients (3.9%) had concentrations greater than 76 pg/mL. In this group, 5
      patients had functioning (VIP, 160-5975 pg/mL) and 5 had nonfunctioning (VIP, 80
      120 pg/mL) pancreatic islet cell carcinomas: all 10 patients had hepatic
      metastases. Other known cases of elevated levels of VIP, ranging from 80 to 340
      pg/mL, included other neurogenic tumors (n = 3), small- bowel resection (n = 2),
      inflammatory bowel disease (n = 2), chronic renal failure (n = 1), and prolonged
      fasting (n = 1). Patients with diarrhea in which VIP-secreting tumors were
      identified had plasma vasoactive intestinal peptide concentrations greater than
      140 pg/mL. In patients with chronic diarrhea, determination of plasma vasoactive
      intestinal peptide levels did identify tumors secreting this peptide, but the
      results from this referral institution did not show identification of these
      tumors early in their clinical course.

PMID- 1983856
TI  - Psychosocial needs of long-term childhood cancer survivors: a review of
      literature.
AB  - With improved medical treatment for childhood cancer, many patients are enjoying
      long disease-free remission or cure. It is important to address the psychosocial
      adjustment of the survivor's life. There are two approaches to the study of
      psychosocial adjustment: study of psychiatric disturbances and assessment of
      quality of life. Incidences of psychiatric disturbances were reviewed with the
      most commonly reported difficulties being depression, anxiety and chemical
      dependency for older survivors and school attendance problems and learning
      difficulties for school age survivors. The assessment of quality of life focused
      on school performance, social adjustment, employment status, independent living
      and marital status. In addition, family coping has received increasing emphasis
      with regard to the effects on marital relationship and financial difficulties,
      although there is no consistent evidence to suggest an increased divorce rate in
      these families. Healthy siblings of cancer survivors are also subject to
      vulnerability. However, there is evidence to suggest most siblings will resolve
      their feelings of jealousy, fear of abandonment and establish a normal sibling
      relationship with the survivor.

PMID- 1983857
TI  - Educational deficits in survivors of childhood cancer.
AB  - Some long-term survivors of childhood cancer experience changes in cognitive
      functioning and have learning difficulties in school. Psychological and
      educational studies of children who received cranial irradiation in treatment for
      acute lymphocytic leukemia or brain tumor have identified specific disabilities.
      A coordinated educational intervention approach is needed, using special
      education services available through local school districts.

PMID- 1983858
TI  - Psychosocial assessment and intervention at initial diagnosis.
AB  - Advances in the long-term survival and possible cure of the child with cancer
      have challenged pediatric professionals to no longer view this child as
      terminally ill, but rather as a developing person with a future. The time of
      initial diagnosis presents the family with coping tasks which, once mastered, lay
      the ground work for future adjustment and, hopefully, the child's eventual return
      to good health. A multidimensional psychosocial assessment can be used to
      identify strengths and difficulties. A range of psychosocial interventions helps
      children and families with the coping tasks of this difficult but challenging
      experience.

PMID- 1983859
TI  - Cancer during adolescence.
AB  - Specific developmental issues and long-term psychosocial implications are
      associated with a diagnosis of cancer during the period of adolescence. Effects
      on the adolescent's developing independence, sexual identity, and social and
      psychological maturity must be considered. Repercussions of these disruptions
      emphasize the need for creative treatment approaches which incorporate both
      immediate and long-term preventive and rehabilitative strategies.

PMID- 1983860
TI  - Late effects of radiation therapy.
AB  - Tissue complications of radiation therapy depend on the interplay of therapy,
      patient and tumor factors. Acute local effects result from parenchymal cell
      hypoplasia. Chronic damage is caused by both injury to parenchymal cells and to
      the underlying vasculature. No body tissue or system is immune to damage from
      radiation therapy, but many effects are dose-dependent. Many of the toxicities
      can currently be avoided by the optimal use of this important cancer therapy.

PMID- 1983861
TI  - Delayed cardiac toxicity from anthracycline therapy.
AB  - Survivors of childhood cancer who received anthracycline treatment have a high
      incidence of abnormal cardiac function. Cardiac decompensation and death can
      appear many years after completion of chemotherapy. These survivors require
      periodic evaluation of cardiac function and rhythm.

PMID- 1983862
TI  - Growth and pubertal development in survivors of childhood cancer.
AB  - Linear growth and final adult stature in survivors of childhood cancer may be
      affected adversely by the disease itself as well as by the treatments utilized.
      The endocrine causes of impaired growth, which include growth hormone deficiency,
      primary thyroid dysfunction, and premature sexual maturation, are generally the
      consequence of radiation therapy. Growth failure is most prominent following
      craniospinal irradiation for brain tumors and total body irradiation for bone
      marrow transplantation. Pubertal development in both males and females is
      generally unaffected by chemotherapy. Leydig cell failure is seen most often
      after direct testicular irradiation with doses greater than 20 Gy. Ovarian
      failure is seen commonly following abdominal, craniospinal and total body
      irradiation.

PMID- 1983863
TI  - Reproductive potential in survivors of childhood malignancy.
AB  - The aggressive use of multiple therapeutic modalities has led to a significant
      increase in the number of survivors of childhood malignancy. These forms of
      cancer therapy have important effects on multiple organ systems. This review
      article evaluates the long-term effect of therapy on the reproductive potential
      of both boys and girls. While alkylating agents have been shown to cause a 50%
      reduction in the fertility potential of boys, they have almost no adverse effect
      in girls. Other chemotherapeutic agents and combinations of chemotherapeutic
      agents have also been shown to cause a greater reduction in the reproductive
      potential of girls than boys. Radiation produces severe dose-related gonadal
      damage in both boys and girls. The effect of Hodgkin's disease, leukemia and
      their therapies are evaluated. Despite the known mutagenic potential of some
      forms of cancer therapy there has not been an increased frequency of congenital
      abnormalities in the offspring of survivors of childhood cancer. The use of
      oophoropexy and other forms of prophylactic therapy to limit toxicity are also
      considered.

PMID- 1983865
TI  - Long-term effects of bone marrow transplantation.
AB  - As increasing numbers of children are surviving beyond the 1st decade after
      marrow transplantation and increasing numbers of children are receiving marrow
      transplants each year, the delayed effects related to the transplant procedure
      itself, the original disease, and/or the transplant preparative regimen are
      becoming apparent. Late effects related to the transplant procedure include those
      of engraftment stability, the chronic immunosuppression of chronic graft-versus
      host disease and delayed immunologic recovery. Recurrent disease is the major
      late effect related to the patient's original disease. The late effects which may
      be related to previous therapy administered and/or the transplant preparative
      regimen include abnormalities of neuroendocrine function, ocular problems, dental
      developmental abnormalities in young children, central nervous system dysfunction
      and the development of secondary malignancies. To improve the quality of life of
      marrow transplant recipients and to prevent some of the growth and development
      abnormalities which may occur, an awareness of the problems encountered to date
      is needed.

PMID- 1983866
TI  - Second malignant neoplasms in survivors of childhood cancer.
AB  - As the treatment of childhood cancer continues to improve, the number of
      survivors at risk for late effects rises. One such late effect is the risk of
      second malignant neoplasms. Large multicenter registries have been established to
      accumulate data on the incidence of second cancers. Relative risks and cumulative
      risks can now be calculated for retinoblastoma, Wilm's tumor and Hodgkin's
      disease. Early data are now available for leukemia, sarcomas and central nervous
      system tumors. Genetic cancer syndromes, radiation therapy and treatment with
      chemotherapeutic agents are known risk factors for second malignant neoplasms in
      survivors of childhood cancer.

PMID- 1983864
TI  - Late effects of allogeneic bone marrow transplantation in children.
AB  - Late sequelae of bone marrow transplantation (BMT) include growth impairment,
      gonadal failure, cataract formation, neurological and pulmonary complications,
      nephropathy, hepatic dysfunction, development of secondary malignancies, chronic
      graft-vs.-host disease, and psychosocial stress. Lifelong follow-up after BMT is
      required to detect late sequelae.

PMID- 1983868
TI  - The Radiological Society of North America (RSNA) index to imaging literature.
      Volumes 166-177(I), 1988-1990.

PMID- 1983867
TI  - The truly cured child?
AB  - The concept of the truly cured child, denoting a child on par with his or her
      peers in development, maturation, achievement, and aspirations, was introduced in
      1977. 'Cure' is the norm in pediatric oncology. However, the cure of a disease
      and the consequences of that disease are complex concepts. Cure has at least
      three components: a biological cure, a psychological cure, and a social cure.
      Biological and psychological cures have been realized, but the social cure is yet
      to be achieved. The concept of the truly cured child is widely accepted. School
      reintegration is the primary method by which psychosocial cure is approached. The
      characteristics of psychosocial cure and the obstacles that hinder uniformly
      achieving the goal should be recognized so that the truly cured child can be a
      realistic goal in pediatric oncology.

PMID- 1983869
TI  - Ultrastructural localization of mRNA encoding for the EGF receptor in human
      breast cell cancer line BT20 by in situ hybridization.
AB  - The EGF receptor (EGF-R), a 170 KD transmembrane glycoprotein, is found at a high
      level in the BT20 human mammary carcinoma cell line (1 +/- 0.4 x 10(6) sites per
      cell). In this study, we examined the expression of the EGF-R gene in BT20 cell
      line by in situ hybridization at the light and electron microscopic level using a
      human cDNA, corresponding to EGF-R transmembrane and protein kinase domains,
      labeled with [3H]-, [35S]-, or [32P]-d-ATP. Two treatments were tested to embed
      cells in Lowicryl resin: the first used fixation and dehydration by progressive
      lowering of temperature, the second quick freezing and cryosubstitution. The best
      ultrastructural preservation was obtained with the second procedure without
      modification of the hybridization signal. EGF-R mRNA was observed principally at
      the cytoplasmic level, on organelles involved in the protein synthesis process.
      Labeling was also located on the microvilli which extend into the intercellular
      space, suggesting that some mRNA would be located in sites where EGF-R is
      utilized. Some mRNA was observed in the nucleus. This study demonstrates that
      post-embedding in situ hybridization, after quick freezing and cryosubstitution,
      is a powerful EM in situ hybridization procedure to study the expression of the
      EGF-R gene.

PMID- 1983870
TI  - Immunoelectron microscopic localization of collagens type I, V, VI and of
      procollagen type III in human periodontal ligament and cementum.
AB  - We examined the ultrastructural localization of collagens Type I, V, VI and of
      procollagen Type III in decalcified and prefixed specimens of the periodontal
      ligament and cementum, by immunoelectron microscopy using ultra-thin cryostat
      sections. Immunostaining for collagen Type I was pronounced on the major cross
      striated fibrils entering cementum and in cementum proper, whereas staining for
      procollagen Type III was almost exclusively observed on the major fibrils in the
      periodontal ligament situated more remote from cementum. Reactivity for collagen
      Type V was limited to aggregated, unbanded filamentous material of about 12 nm
      diameter that was found mainly in larger spaces between bundles of cross-striated
      collagen fibrils and occasionally on single microfibrils that apparently
      originated from the ends of the major collagen fibrils, which may support the
      concept of this collagen as a component of core fibrils. Collagen Type VI was
      present as microfilaments appearing to interconnect single cross-striated
      fibrils. In the densely packed fibril bundles of the periodontal ligament, no
      collagen type VI was detected. Neither Type V or Type VI collagen was observed in
      cementum.

PMID- 1983871
TI  - An electrophoretic method for selection of conditions for production of
      electrophoretically uniform protein colloidal gold complexes.
AB  - An electrophoretic method was developed to determine the conditions required for
      production of electrophoretically uniform protein-colloidal gold complexes from
      monodisperse colloidal gold (Au) and electrophoretically uniform protein. The
      method is based on the electrophoretic migration of protein-Au complexes in
      agarose. The results demonstrate that two variables, the pH of adsorption and the
      quantity of protein added, can be manipulated to vary the electrophoretic
      mobility of the resulting protein-Au complexes. Thus, agarose gel electrophoresis
      can be used to select the pH of adsorption and the quantity of protein required
      to produce electrophoretically uniform protein-Au complexes. This new
      electrophoretic mobility test can be used in place of or in addition to the
      classical procedure of Zsigmondy and its many variations, both visual and
      spectrophotometric. The procedure described is also useful for electrophoretic
      comparison of small quantities of various protein-Au samples.

PMID- 1983872
TI  - Commercial preparations of colloidal gold-antibody complexes frequently contain
      free active antibody.
AB  - Using a simple fluorescence test, we show that commercially prepared colloidal
      gold complexes with goat second antibodies often contain free active antibody.
      Because such antibodies will compete with antibody-colloidal gold particles for
      antigen binding sites, labeling intensity at the ultrastructural level must
      necessarily be submaximal to an unknown degree with such preparations. A survey
      of five preparations suggests that the problem may be widespread. We recommend
      that a test of the sort described be incorporated routinely into protocols with
      all colloidal gold products.

PMID- 1983873
TI  - Rotary shadowing of collagen monomers, oligomers, and fibrils during tendon
      fibrillogenesis.
AB  - Collagen monomers, oligomers, and fibrillar structures were isolated from chick
      tendons at various stages of development and studied by rotary shadowing.
      Monomers of Type I collagen, solubilized in 0.15 M NaCl solutions, were mostly
      present as collagen, pN-collagen, and pC-collagen with few procollagen molecules.
      They did not form polymers, nor were they associated with a carrier. Dimers of
      fibrillar collagen molecules were arranged in a 4-D stagger, suggesting that this
      was the preferred molecular interaction for the initiation of collagen
      fibrillogenesis. Type XII collagen molecules were mostly free, but some were
      attached by their central globular domain to one end of free fibrillar collagen
      molecules. Tenascin and Type VI collagen were also identified. The fibril
      populations consisted of collagen and beaded structures. These fibrils consisted
      of beads (globular domains) about 23 nm in diameter, separated by a period about
      27 nm in length. Beads were linked by filamentous structures. These beaded
      fibrils probably represent the microfibrils of elastin.

PMID- 1983874
TI  - Human bone contains type III collagen, type VI collagen, and fibrillin: type III
      collagen is present on specific fibers that may mediate attachment of tendons,
      ligaments, and periosteum to calcified bone cortex.
AB  - We evaluated the distribution of Type III collagen, Type VI collagen, and
      fibrillin in human bone, using monoclonal antibodies (MAb) of proven specificity.
      All three molecules are present in developing and remodeling bone. Type III
      collagen is present in discrete fiber bundles throughout the bone cortex but is
      concentrated at the Haversian canal surface and in the fibers at the bone
      periosteal interface. The collagen fibrils in these bundles are of uniform
      diameter. Type III-containing collagen fibers are detected at all ages examined,
      from 30 fetal weeks to 80 years. Type VI collagen is present in fetal bone in
      discrete fibrils separate from Type III collagen, and becomes restricted to the
      margins of bone cells and the bone surface by 7 years. The distribution of
      fibrillin resembles that of Type III collagen in the fetus, but at 7 years is
      absent from the interior of the cortex except for the canaliculi and cement
      lines, and remains concentrated in discrete fibers at the bone surface.

PMID- 1983875
TI  - Heterogeneity of glycoconjugates in the secretory cells of the chinchilla middle
      ear and eustachian tubal epithelia: a lectin-gold cytochemical study.
AB  - The present study was conducted to characterize and localize the glycoconjugates
      in the tubotympanum (auditory or eustachian tube and middle ear cavity) of
      chinchilla on an ultrastructural level, using lectin-gold complexes with six
      different lectins: BPA, ConA, RCA-1, WGA, LFA, and SNA. A comparison of the
      affinity of these lectins demonstrated the heterogeneity of secretory cells. The
      glandular serous cells and epithelial dark granulated cells produced "serum"-type
      glycoprotein. The glandular mucous cells and goblet cells produced dominantly
      "mucin"-type glycoprotein in the light granules, but "serum"-type glycoprotein in
      the dark cores. The labeling of LFA and SNA showed that sialic acids existed
      mainly in the mucinous granules of secretory cells and ciliated epithelium
      glycocalyx, and in the mucous blanket. The results also suggested that the
      dominant linkage of sialic acids of mucin is a Neu5Ac(alpha 2-6)Gal/GalNAc
      sequence. Furthermore, the data obtained from ConA and BPA suggested that initial
      O-glycosylation of mucin took place in the cis side of the Golgi apparatus and
      that initial N-glycosylation of the serum occurred in the rough endoplasmic
      reticulum.

PMID- 1983876
TI  - Localization of xanthine oxidoreductase activity using the tissue protectant
      polyvinyl alcohol and final electron acceptor Tetranitro BT.
AB  - We have detected xanthine oxidoreductase activity in unfixed cryostat sections of
      rat and chicken liver, rat duodenum, and bovine mammary gland using the tissue
      protectant polyvinyl alcohol, the electron carrier 1-methoxyphenazine
      methosulfate, the final electron acceptor Tetranitro BT, and hypoxanthine as a
      substrate. Enzyme activity was localized in rat duodenum at lateral membranes and
      brush borders of enterocytes and in goblet cells and mucus. Hepatocytes in
      pericentral areas and especially sinusoidal cells showed high activity in rat
      liver. Xanthine oxidoreductase was also detected in epithelial cells and milk
      lipid globules of lactating bovine mammary gland, which is known to contain large
      quantities of the oxidase form of the enzyme. Chicken liver, which contains an
      inconvertible dehydrogenase form, also showed high activity in sinusoidal cells.
      Therefore, we conclude that the tetrazolium reaction demonstrates both the
      dehydrogenase and the oxidase form of xanthine oxidoreductase. Control activity,
      in the absence of hypoxanthine or in the presence of the competitive inhibitor
      allopurinol, was low in all tissues studied. Addition of O2 or NAD to the
      incubation medium did not change the specific reaction in bovine mammary gland or
      chicken liver, implying that the dehydrogenase and the oxidase form are not
      dependent on their natural electron acceptors in this tetrazolium salt reaction.
      We conclude that the present light microscopic method gives specific and precise
      localization of xanthine oxidoreductase activity in situ.

PMID- 1983877
TI  - Unilateral hydrocephalus in adults.
AB  - The authors report 14 cases of unilateral hydrocephalus in adults. Headache was
      the most common presenting symptom. Unilateral hydrocephalus was documented in
      each patient with computed tomography scans; magnetic resonance imaging was also
      used in seven patients in the latter part of the series. Unilateral hydrocephalus
      was caused by tumor (seven patients), venous angioma (one patient), ependymal
      cyst (one patient), postinflammatory gliosis (one patient), and was idiopathic in
      four patients. The primary surgical treatment was craniotomy with fenestration of
      the septum pellucidum, which relieved symptoms in eight of nine patients for whom
      long-term follow-up data were available.

PMID- 1983878
TI  - Cerebrospinal fluid endothelin-1 and endothelin-3 levels in normal and
      neurosurgical patients: a clinical study and literature review.
AB  - Endothelins are a family of structurally related, potent, long-lasting
      vasoconstrictor peptides. There are no established normal human levels of
      endothelin-1 or endothelin-3 in the cerebrospinal fluid. We measured
      cerebrospinal fluid endothelin-1 and endothelin-3 levels in five groups of
      patients: normal controls, patients with subarachnoid hemorrhage and cerebral
      vasospasm, patients with severe head injuries, patients undergoing temporal
      lobectomy for intractable epilepsy, and a patient with a gunshot injury to the
      thoracic spine. Endothelin-3 levels were significantly elevated in patients with
      subarachnoid hemorrhage and may participate in cerebral vasospasm and subsequent
      neurologic deterioration.

PMID- 1983879
TI  - Transcranial Doppler ultrasound following closed head injury: vasospasm or
      vasoparalysis?
AB  - Nine patients suffering closed head injury were studied using transcranial
      Doppler ultrasound recording of the basal cerebral arteries. On admission, six
      patients had Glasgow Coma Scores of 7 or less, while three had initial scores of
      8-10. Eight of the nine patients (82%) developed abnormally high mean velocities
      (greater than or equal to 110 cm/s) in one or more vessels. The onset, duration,
      and amplitude of the altered flow velocities were somewhat different from those
      that are seen with vasospasm after aneurysmal subarachnoid hemorrhage, which tend
      to occur later. Cerebral angiography in one of the study patients confirmed the
      presence of vasospasm. Multivariate regression analysis showed a definite
      correlation between the velocities recorded, even when abnormally elevated, and
      concurrent pH and PCO2 measurements (p = 0.01, R2 = 0.23). Although these results
      suggest that the cerebral vasculature retains its vasoreactivity following head
      injury, arguing against vasoparalysis, inconsistencies found in some of the
      patients lead us to think that both vasospasm and vasoparalysis may occur
      following head trauma but that they may have different temporal profiles.

PMID- 1983880
TI  - Continuous postoperative monitoring of cortical blood flow and intracranial
      pressure.
AB  - A new technique to continuously monitor cortical blood flow and intracranial
      pressure in postoperative patients is described. A thermal diffusion flow probe
      with a pressure port is left in contact with the cortex at craniotomy.
      Postoperative intracranial pressure--cortical blood flow can be monitored and
      acute changes or trends are readily detected. The thermal flow probe has been
      previously compared with radioactive xenon (133Xe) clearance and hydrogen
      clearance methods of measuring cortical blood flow in animals. The technique
      gives a real-time quantitative indication of flow. Changes in cortical blood flow
      can be observed within a few seconds and the effects of treatment can be readily
      observed. Changes in flow due to vasospasm have been demonstrated in subarachnoid
      hemorrhage. It is anticipated that information learned from this method will aid
      in the management of patients with head trauma, tumors, and subarachnoid
      hemorrhage.

PMID- 1983881
TI  - Multiple arterial fenestrations, multiple aneurysms, and an arteriovenous
      malformation in a patient with subarachnoid hemorrhage.
AB  - We report the case of a 49-year-old, right-handed man with multiple vascular
      pathologies, including a fenestrated anterior communicating artery and middle
      cerebral artery, an aneurysm of the anterior communicating artery, multiple
      aneurysms of the middle cerebral artery, and an arteriovenous malformation.
      Diagnoses were made through computed tomography, cerebral angiography, magnetic
      resonance imaging, and intraoperative dissection. The lesions were managed
      surgically in stages with satisfactory results. Congenital and hemodynamic
      factors may have combined to manifest in the anomalies present in this unique
      case. We believe that no similar combination of vascular pathology has been
      reported previously.

PMID- 1983883
TI  - W. James Gardner, M.D. June 12, 1898-January 29, 1987.

PMID- 1983882
TI  - Familial trigeminal neuralgia and Charcot-Marie-Tooth neuropathy. Report of two
      families and review.
AB  - Typical trigeminal neuralgia has occasionally occurred in multiple members of the
      same family over several generations. The clinical features of such cases,
      including the increased incidence in females, and the absence of other apparent
      hereditary, neurologic, metabolic, or structural abnormalities were identical to
      those of sporadic cases. More rarely, familial trigeminal neuralgia has been
      described in the setting of hereditary peripheral neuropathy, especially Charcot
      Marie-Tooth disease. We describe patients from two different families with
      Charcot-Marie-Tooth disease and medically intractable trigeminal neuralgia. Both
      patients were successfully treated by percutaneous retrogasserian glycerol
      rhizolysis. The occurrence of cranial nerve symptoms in patients with
      demyelinating peripheral neuropathies is discussed in light of the current
      hypotheses regarding the etiology of trigeminal neuralgia.

PMID- 1983884
TI  - Two cases of fatal atlantoaxial distraction injury without fracture or rotation.
AB  - Atlantoaxial injuries, regardless of mechanism, typically result in bony injury.
      We present two unusual cases of fatal traumatic C-1-C-2 distraction without
      associated fracture or rotation. The ligamentous anatomy, common underlying
      structural/medical predispositions, and the possible mechanism of injury are
      discussed.

PMID- 1983885
TI  - Eosinophilic granuloma of the cervical spine. A case report and review of the
      literature.
AB  - This is a report of a case of eosinophilic granuloma involving the second
      cervical vertebra in a 33-year-old woman. There have been 32 case reports in the
      literature describing eosinophilic granuloma presenting as cervical spine
      disease. Due to its intimate relation to the central nervous system, the
      opportunity for neurological sequelae and neurosurgical intervention is common in
      cervical eosinophilic granuloma. In this report a brief history of eosinophilic
      granuloma is reviewed and case histories from the literature with cervical spine
      involvement are summarized. The therapeutic options are described and a
      recommended protocol for management is outlined.

PMID- 1983887
TI  - The contributions of Harvey Cushing to the techniques of neurosurgery.

PMID- 1983886
TI  - Interventional neurovascular treatment of a giant intracranial aneurysm using
      platinum microcoils.
AB  - A 70-year-old woman presented with symptoms of progressive cerebellar dysfunction
      due to mass effect from a giant, expanding, posterior fossa aneurysm arising from
      the distal vertebral artery. The aneurysm contained thrombus and had a broad
      based neck. From a transfemoral approach, with the patient under local
      anesthesia, a 2.2 French microcatheter was guided through the vertebral artery
      and placed directly into the aneurysm. Six 5 x 15-mm platinum microcoils were
      deposited into the residual lumen of the aneurysm, resulting in complete
      thrombosis with obliteration of the aneurysm and preservation of the parent
      artery. Endovascular coil embolization therapy by interventional neurovascular
      techniques may provide a therapeutic alternative in the management of surgically
      difficult symptomatic intracranial aneurysms.

PMID- 1983888
TI  - Euthanasia: the "good death"?
AB  - The changing attitude of some medical practitioners in certain countries condones
      the practice of euthanasia. This article examines the scope of attitudes toward
      life and death, suggesting moral and ethical considerations regarding euthanasia.

PMID- 1983889
TI  - Turkish neurosurgery.

PMID- 1983890
TI  - Extraaxial.

PMID- 1983891
TI  - Intracranial nonspecific inflammatory granuloma.

PMID- 1983892
TI  - Neurosurgeons must fight animal activists.

PMID- 1983893
TI  - Some issues in graduate medical education.

PMID- 1983894
TI  - Assessment of the prevalence and risk factors for human immunodeficiency virus
      type 1 (HIV-1) infection among college students using three survey methods.
AB  - To evaluate the seroprevalence and risk factors for human immunodeficiency virus
      type 1 (HIV-1) infection among undergraduate college students, the authors
      simultaneously conducted three types of surveillance on a large university campus
      (27,902 undergraduates) in the Baltimore-Washington metropolitan area: a
      voluntary HIV-1 serosurvey with a linked risk assessment questionnaire (n =
      3,394), a blinded serosurvey using blood specimens collected for routine purposes
      in the Student Health Center (n = 1,829), and a random sample risk assessment and
      case identification mail survey (n = 1,017 respondents of 3,000 solicited). The
      proportion of students belonging to a known risk group (a homosexual or bisexual
      man, intravenous drug user, or a sexual partner of a bisexual man, an HIV-1
      infected person, a female prostitute, or an intravenous drug user) was 5.9% in
      the mail survey and 8.8% in the voluntary serosurvey. Whereas no infections were
      detected in the blinded serosurvey, two infected persons were identified in the
      mail survey (0.2%) and two in the voluntary serosurvey (0.06%), all among high
      risk persons. Although derived from independent samples and subject to different
      biases, these three survey methods yielded a consistent pattern of HIV-1
      epidemiology on this campus, whereby the overall prevalence of infection was low
      and confined to members of high-risk groups, despite the common occurrence of
      behaviors that might facilitate sexual transmission of HIV-1 among many other
      students.

PMID- 1983895
TI  - Diet and peripheral arterial occlusive disease: the role of poly-, mono-, and
      saturated fatty acids.
AB  - A case-control study concerning the association between diet and peripheral
      arterial occlusive disease was conducted in Athens, Greece. The case series
      consisted of 100 patients with this disease, whereas controls were 100 patients
      with conditions requiring minor surgical care who were admitted to the same
      teaching hospital. Diet was ascertained through a semiquantitative food frequency
      questionnaire. Nutrient intakes for individuals were estimated by multiplying the
      nutrient content of a selected typical portion size for each specified food item
      by the frequency that the food was used per month and summing these estimates for
      all food items. Data were analyzed using multiple logistic regression procedures,
      controlling for total energy intake by taking nutrient residuals and by using
      multivariate nutrient density models. Saturated fatty acids (odds ratio (OR) and
      95% confidence interval (CI) contrasting the 75th centile (upper) with the 25th
      centile = 1.96 and 1.14-3.39), proteins (OR = 2.86, 95% CI 1.47-5.55), and
      dietary cholesterol (OR = 6.07, 95% CI 2.74-13.46) were associated with increased
      risk of peripheral arterial occlusive disease, whereas polyunsaturated fatty
      acids (OR = 0.48, 95% CI 0.24-0.93) and crude fiber (OR = 0.33, 95% CI 0.17-0.64)
      were related to reduced risk. Monounsaturated fatty acids and, by inference,
      olive oil occupy an intermediate neutral position between polyunsaturates and
      saturates (corresponding OR = 1.14, 95% CI 0.68-1.91). Higher intakes of fiber
      and vitamin C were associated with lower risk of peripheral arterial occlusive
      disease. The low occurrence of atherosclerotic diseases in Greece and other
      Mediterranean countries may be due to the substitution of olive oil in place of
      saturated fats and/or the consumption of a diet high in vegetables, fruits, and
      other fiber-containing foods.

PMID- 1983896
TI  - Oral contraceptive estrogen dose and the risk of deep venous thromboembolic
      disease.
AB  - Despite the well-recognized association between oral contraceptives and deep
      venous thromboembolism, little is known about the risks associated with currently
      marketed formulations containing less than 50 micrograms of estrogen. To assess
      the venous thrombogenicity of low-estrogen oral contraceptives (those containing
      less than 50 micrograms of estrogen) relative to intermediate-dose (50 micrograms
      of estrogen) and high-dose (greater than 50 micrograms of estrogen) formulations,
      we conducted a cohort study of oral contraceptive users between the ages of 15
      and 44 years in the Michigan Medicaid population. The period of the study was
      from 1980 through the third quarter of 1986. A total of 2,739,400 oral
      contraceptive prescriptions received by 234,218 women were analyzed. Using the
      low-estrogen cohort as the referent group, the age and calendar period adjusted
      relative risk of venous thromboembolism in users of intermediate-dose
      formulations was 1.5 (95% confidence interval (CI) 1.0-2.1, p = 0.04), and the
      relative risk in users of high-dose formulations was 1.7 (95% CI 0.9-3.0, p =
      0.06). These data provide evidence that the dose-response relation between oral
      contraceptive estrogen and venous thromboembolism extends from 50 to 30
      micrograms of estrogen, the dose range of currently marketed formulations.

PMID- 1983897
TI  - The association between weight, physical activity, and stress and variation in
      the length of the menstrual cycle.
AB  - The association between weight, physical activity, and stress and variation in
      the length of the menstrual cycle was prospectively examined in 166 college
      women, aged 17-19 years, who kept menstrual diaries during their freshman year.
      The unadjusted probability of a menstrual cycle being longer than 43 days was 5%.
      Women with a history of long cycles were more likely to have a long cycle during
      the study (odds ratio (OR) = 4.3). Stressors, characterized by situations which
      create a demand for performance or require adjustments to new demands, also
      increased the risk of a long cycle. Odds ratios for gain events and for coping
      with multiple performance demands (2 vs. 0) were 1.9. Starting college increased
      the risk of long cycles (OR = 2.3) regardless of whether a woman had left home.
      Moderate exercise minimally increased the probability of a long cycle (OR = 1.1,
      75th vs. 50th percentiles). Change in weight (OR = 1.9) and being overweight (OR
      = 1.2, 15% above standard weight for height) were independently associated with
      the probability of long cycles. When 17- to 43-day cycles were evaluated, a
      history of long cycles lengthened expected cycle length by 1.42 days, while
      dieting, living on campus, and starting college tended to shorten expected length
      by 1.38, 0.90, and 0.64 days, respectively. Further investigation of the biologic
      mechanisms that mediate the stress effect is warranted.

PMID- 1983898
TI  - Reliability and interrelations among serum sex hormones in postmenopausal women.
AB  - Serum sex hormones may be related to the risk of several diseases in
      postmenopausal women including osteoporosis, heart disease, and breast and
      endometrial cancer. For assessment of the relation of sex hormones to disease,
      the measurements should be reliable, valid, and practical. In this paper, the
      authors evaluated the short-term (4-week) and long-term (2-year) reliability of
      serum sex hormones and interrelations among serum sex hormones in white
      postmenopausal women recruited in Pittsburgh, Pennsylvania, 1981-1986. For
      comparison, the authors simultaneously evaluated the short- and long-term
      reliability of other commonly measured risk factors, i.e., lipids, lipoproteins,
      and blood pressure. Serum concentrations of estrone, estradiol, testosterone, and
      androstenedione were measured by extraction, column chromatography, and
      radioimmunoassay. Reliability was estimated by calculating the intraclass
      correlation coefficients (R) and their 95% confidence interval. About 50% of the
      estradiol levels were below the sensitivity of the assay and, therefore, these
      results should be interpreted with some caution. The intraclass correlation
      coefficient for testosterone was 0.92 (95% confidence interval 1.0-0.82),
      suggesting that a single measure may be reliable in characterizing women for
      epidemiologic research. Over 4 weeks, estrone could be measured more reliably (R
      = 0.72) than over 2 years (R = 0.56), but the variability over the long term was
      similar to that observed for other biologic variables, suggesting that, in
      situations where the relation between estrone and disease is fairly substantial,
      a single measure may be used. For estradiol and androstenedione, the intraclass
      correlations were small, indicating poor reproducibility and the need for more
      measurements. Estrone concentrations were 11 pg/ml or 46% higher in women with
      measurable estradiol. Estrone was also positively related to androstenedione
      concentrations (r = 0.33, p less than 0.001). Concentrations of estradiol are
      extremely low in postmenopausal women, and accordingly, there is a greater
      possibility of laboratory error. Since the data suggest that estrone levels can
      be more reliably measured and are, in fact, related to estradiol levels, it is
      possible that estrone levels may be used to indicate the total estrogen status of
      postmenopausal women.

PMID- 1983899
TI  - The effects of changes in health care delivery on the reported incidence of
      cutaneous melanoma in western Washington State.
AB  - The reported incidence of malignant melanoma of the skin has steadily increased
      in the United States during the past three decades. Since the treatment of
      melanoma increasingly has been provided solely on an outpatient basis in recent
      years, it is likely that some cases of this disease are being missed by
      population-based tumor registries that do not consistently ascertain cases from
      sources outside the hospital setting. The population-based tumor registry of
      western Washington state has been identifying office-treated cases of cutaneous
      melanoma from records of private and hospital pathology laboratories. However,
      since laboratory records have often lacked information on place of residence,
      these cases have not been previously included in the calculation of incidence
      rates. In the present study, by determining the place of residence of these cases
      at the time of their diagnosis (by contacting the physician listed on their
      pathology reports), the authors found that there had been a growing amount of
      underreporting of cutaneous melanoma from 1974 through 1984. In western
      Washington state, the incidence of melanoma of the skin had been underestimated
      in registry rates by approximately 2% in 1974 and approximately 21% in 1984. This
      trend in the level of underenumeration has spuriously blunted the true increasing
      incidence of melanoma and may limit the ability to monitor and study this disease
      in the future.

PMID- 1983900
TI  - The investigation of age at onset as a risk factor for mortality in persons with
      insulin-dependent diabetes mellitus using Cox proportional hazards models.
AB  - Proportional hazards models measuring the effect of age at onset of insulin
      dependent diabetes mellitus on mortality risk are presented. The study population
      consisted of 924 insulin-dependent diabetic patients who were seen within 1 year
      of diagnosis at Children's Hospital of Pittsburgh between 1950 and 1981 and were
      more than 20 years old at follow-up. Age at diabetes onset was categorized as
      prepubertal or pubertal, defined by age. Individuals with pubertal onset of
      diabetes had a significantly higher risk of mortality compared with those with
      prepubertal onset by diabetes duration but not by attained age. It is proposed
      that age at onset is an independent determinant of mortality in diabetic
      individuals and may represent either heterogeneity within insulin-dependent
      diabetes mellitus with respect to long-term prognosis or an interactive effect of
      diabetes duration and puberty on prognosis.

PMID- 1983901
TI  - Validation of the physical activity instrument for the Life in New Zealand
      national survey.
AB  - A physical activity recall instrument suitable for self-administration by the
      adult New Zealand population was devised and validated for 140 subjects selected
      randomly from urban electoral rolls. Validation used bootstrapping to compare
      correlations between subjective measures derived from the instrument, the
      Stanford 7-day recall questionnaire and other questionnaires, and objective
      measures derived from an exercise test. Subjective measures were grouped as
      measures of high intensity activity, low intensity activity, or total activity
      metabolism. The high intensity measures correlated moderately with each other
      (mean r = 0.39), but poorly with metabolism and low intensity measures (r = 0.16,
      -0.02, respectively). The mean correlation between the metabolism and low
      intensity groups (r = 0.26) was similar to those within these groups (r = 0.31,
      0.25, respectively). Thus, the high intensity measures formed a group distinct
      from the metabolism and low intensity groups, which represented similar measures.
      The objective measures that correlated with high intensity measures (mean r =
      0.25) are predominantly recognized risk factors for cardiovascular disease; these
      did not correlate with the metabolism or low intensity measures (mean r = 0.03, 
      0.07, respectively). Activity measures from the instrument had mean correlations
      with subjective and objective measures that equaled or surpassed those of the
      Stanford measures from the same group. The authors conclude that 1) population
      health studies that assay physical activity should include well-defined measures
      of high intensity activity, and 2) valid measures of physical activity in the New
      Zealand population are achievable with this instrument.

PMID- 1983902
TI  - Nonresponse and intensity of follow-up in an epidemiologic study of Vietnam-era
      veterans.
AB  - Characteristics of nonrespondents, respondents who were easy to locate, and
      respondents who were hard to locate were examined with the use of data from a
      telephone health survey of male, US Army, Vietnam-era veterans. Of 17,867
      eligible men discharged from active military duty in the late 1960s and early
      1970s, 15,288 (86%) were successfully located and interviewed during 1985-1986.
      Veterans who could not be located were more likely than respondents to possess
      baseline characteristics predictive of increased mortality. In contrast, subjects
      who were located but refused to be interviewed were similar to respondents. Among
      veterans who were interviewed, those who were hardest to locate had the highest
      prevalence of known risk factors for diminished health status and reported many
      health problems with higher relative frequencies than respondents who were easier
      to locate. Odds ratios comparing the prevalence of each of 11 health outcomes in
      men who had served in Vietnam with that in men who had served elsewhere did not
      vary appreciably by intensity of follow-up. In particular, the subgroup of
      respondents that was located and interviewed within 2 weeks of initiation of
      follow-up (comprising 25% of all respondents) produced odds ratios for 10 of the
      11 outcomes that were not appreciably different from odds ratios based on all
      respondents.

PMID- 1983903
TI  - Diet, body size, and plasma lipids-lipoproteins in young adults: differences by
      race and sex. The Coronary Artery Risk Development in Young Adults (CARDIA)
      study.
AB  - The Coronary Artery Risk Development in Young Adults (CARDIA) study completed
      baseline dietary assessment, measurement of body mass index, and lipid and
      lipoprotein analyses on 5,111 participants. CARDIA includes black and white men
      and women between 18 and 30 years of age at baseline (1985-1986), recruited in
      Birmingham, Alabama, Chicago, Illinois, Minneapolis, Minnesota, and Oakland,
      California. Diet was assessed by a detailed interviewer-administered diet history
      that measured the usual eating pattern over the past month. Possible sex, race,
      age, and educational differences in diet, body size, and lipids-lipoproteins were
      explored. Nutrient analyses indicate that the Keys score, a measure of dietary
      fat composition, is significantly correlated with plasma cholesterol in older
      (aged 25-30 years) white men (r = 0.12, p less than 0.01) and older white women
      (r = 0.12, p less than 0.001). In multiple linear regression analyses, body mass
      index was positively and significantly associated with total cholesterol and low
      density lipoprotein cholesterol and inversely associated with high density
      lipoprotein cholesterol across all race-sex groups. The Keys score was
      significantly associated with total cholesterol and low density lipoprotein
      cholesterol in white men and women. Education was associated with high density
      lipoprotein cholesterol in black and white women and white men. In these young
      adults, dietary fat intake and body mass index were related to blood lipids in
      certain subgroups. In black and white men and black women, blood cholesterol
      increased with age across race-sex groups independently of these covariates. In
      view of the many factors affecting plasma cholesterol and the limitations of the
      dietary history method, these cross-sectional data are useful in characterizing
      diet and lipid differences. There appears to be general disparity between
      recommended dietary intake of total fat, saturated fat, and other nutrients and
      actual dietary intake in young adults, regardless of age and educational level.

PMID- 1983904
TI  - The status of restrictive smoking policies: a survey of medical schools in the
      United States and Canada.
AB  - All schools of medicine in the United States (N = 128) and Canada (N = 16) were
      surveyed by telephone to determine if they had instituted policies to restrict
      smoking. Some policy restricting smoking was reported by 80.56 percent of US
      schools (N = 103) and by 93.8 percent of Canadian schools (N = 15). However, only
      52.3 percent of US (N = 67) and 56.3 percent of Canadian medical schools (N = 9)
      indicated they had formal written policy statements. Only 13 percent of US
      schools and 19 percent of Canadian schools had banned smoking totally.

PMID- 1983905
TI  - Measurement of attitudes and behaviors in public health surveys.
AB  - We divided 900 general practitioners into two groups: one group received a
      questionnaire measuring both attitudes and behaviors toward preventive aspects of
      medical care, while the other received two separate questionnaires--one measuring
      behaviors, and one measuring attitudes. Response rates of the two groups were
      similar. Respondents in the first group retrieved their answer to the attitudinal
      items when responding to behavioral items, increasing the correlations between
      attitudes and behaviors by an average of .147 as compared to the second group;
      hence the second procedure was preferable.

PMID- 1983906
TI  - Determinants of condom use among French heterosexuals with multiple partners.
AB  - In September 1988, a sample of French individuals between 18 and 49 years of age,
      who reported more than one sexual partner in the past six months and who
      considered themselves heterosexuals (n = 1088), were interviewed at home about
      risk perception of human immunodeficiency virus (HIV) transmission, sexual
      behavior, and condom use. Systematic or occasional use of condoms during the
      previous 12 months was reported by 46.9 percent of respondents. Among condom
      users, 38.7 percent declared they had never used condoms before the last 12
      months, fear of acquired immunodeficiency syndrome (AIDS) rather than
      contraception being the main motivation of these recent users. Multivariate
      analysis indicates that voluntary testing for HIV, average or more than average
      fear of sexually transmitted diseases (STDs), and knowledge of HIV carrier in
      personal relations are associated with condom use.

PMID- 1983907
TI  - Congenital syphilis criteria.

PMID- 1983908
TI  - It's only oil, it's only money!!!

PMID- 1983909
TI  - What makes infant mortality rates fall in developing countries?

PMID- 1983910
TI  - Social origins, medical education, and medical practice.

PMID- 1983911
TI  - Disease control priorities in developing countries: health policy responses to
      epidemiological change.
AB  - Health systems in developing countries are facing major challenges in the 1990s
      and beyond because of a growing epidemiological diversity as a consequence of
      rapid economic development and declining fertility. The infectious and parasitic
      diseases of childhood must remain a priority at the same time the chronic
      diseases among adults are emerging as a serious problem. Health policymakers must
      engage in undertaking an epidemiological and economic analysis of the major
      disease problems, evaluating the cost-effectiveness of alternative intervention
      strategies; designing health care delivery systems; and, choosing what
      governments can do through persuasion, taxation, regulation, and provision of
      services. The World Bank has commissioned studies of over two dozen diseases in
      developing countries which have confirmed the priority of child survival
      interventions and revealed that interventions for many neglected and emerging
      adult health problems have comparable cost-effectiveness. Most developing
      countries lack information about most major diseases among adults, reflecting
      lack of national capacities in epidemiological and economic analyses, health
      technology assessment, and environmental monitoring and control. There is a
      critical need for national and international investment in capacity building and
      essential national health research to build the base for health policies.

PMID- 1983912
TI  - Patterns of medical employment: a survey of imbalances in urban Mexico.
AB  - This article quantifies the magnitude and correlates of the major imbalances
      affecting the employment of physicians in the urban areas of Mexico. Since the
      early 1970s the country has experienced a rapid increase in the supply of
      doctors, which its health system was unable to absorb fully. In 1986, we
      conducted a survey in the 16 most important cities based on a probability sample
      of households where someone with an MD degree lived. A total of 604 physicians
      were interviewed for a response rate of 97 percent. The unemployment rate was 7
      percent of potentially active physicians; 11 percent held a nonmedical job, and
      another 11 percent exhibited low productivity and/or income. All in all, we
      project that 23,500 physicians in these cities were either unemployed or
      underemployed. This medical employment pattern was analyzed against five
      independent variables: generation (i.e. the year in which the physician started
      medical school), gender, social origin, medical school quality, and specialty.
      Apart from generation, type of specialty exhibited the strongest correlation with
      the employment situation of a physician. The results suggest that higher
      education and health care in Mexico may be producing rather than correcting
      social inequalities. Policy alternatives are discussed to restore a balance
      between the training of physicians, their gainful employment, and the health
      needs of the population.

PMID- 1983913
TI  - Why do child mortality rates fall? An analysis of the Nicaraguan experience.
AB  - A comprehensive review of available sources of mortality data was undertaken to
      document the changes that have occurred in infant mortality in Nicaragua over the
      last three decades. It was found that a rapid fall in infant mortality commenced
      in the early 1970s and has continued steadily since. Trends in several different
      factors which might have led to this breakthrough were examined including:
      income, nutrition, breastfeeding practices, maternal education, immunizations,
      access to health services, provision of water supplies and sanitation, and anti
      malarial programs. Of these, improved access to health services appears to have
      been the most important factor. At a time when the number of hospital beds per
      capita was dropping, increasing numbers of health care professionals,
      particularly nurses, were becoming available to staff primary health care
      facilities built in the 1960s. These were provided at least partly in response to
      the growing political turmoil enveloping the nation at that time. Certain
      Nicaraguan cultural attributes may have added to the impact of the reforms.
      Efforts in the field of public health made since the 1979 insurrection appear to
      have maintained the decline in child mortality.

PMID- 1983915
TI  - Maternal feeding behavior and child acceptance of food during diarrhea,
      convalescence, and health in the central Sierra of Peru.
AB  - Feeding patterns by mothers and child acceptance of food were measured in a
      Peruvian village to determine changes on days when children had diarrhea as
      compared to days of convalescence and health. Morbidity surveillance identified
      40 children, aged 4-36 months, with diarrhea. Children were followed using twelve
      hour in-home structured observations during two to four days each of diarrhea,
      convalescence, and health. Using scales of maternal encouragement to eat and
      child acceptance of food and cumulative logistic regression analyses, maternal
      encouragement to eat decreased significantly during convalescence compared to
      diarrheal days (OR: 0.54, 90% CI: 0.35, 0.82) and health compared to diarrhea
      (OR: 0.65, 90% CI: 0.46, 0.93). In contrast, child acceptance of food increased
      during health compared to diarrhea (OR: 1.55, 90% CI: 1.02, 2.35). Results
      illustrate the importance of carefully examining the behavioral aspects of
      nutritional intake. Decreases in intake during diarrhea are due to anorexia and
      not withdrawal of food by mothers. In response to reductions in child appetite
      during illness, mothers are more likely to encourage children to eat, while they
      tend to become more passive feeders after the diarrhea has stopped. Program
      efforts should focus on messages to feed children more actively especially after
      diarrhea episodes, when appetite levels increase.

PMID- 1983914
TI  - The role of attitudes, beliefs, and personal characteristics of Italian
      physicians in the surgical treatment of early breast cancer.
AB  - The influence of Italian physicians' attitudes, beliefs, and personal
      characteristics on medical decision making is examined in the case of surgical
      treatment of early breast cancer. Responses to a mail survey of 657 physicians
      from different specialties were analyzed comparing doctors recommending a radical
      procedure (9%) to those preferring a conservative procedure for younger patients
      only (25%), and those considering conservative surgery the treatment of choice
      regardless of patients' age (66%). The findings suggest that the likelihood of
      physicians' preferring a conservative procedure is influenced by their specialty
      and the extent to which they feel that a patient should have a role in the
      treatment decision more than by differences in the beliefs of treatment outcomes.
      Only preferences of the small group indicating radical surgery as the sole
      admissible treatment can be accounted for by ignorance or distrust of results of
      recent trials. These findings suggest that other than scientific factors guide
      many doctors in their decision making; they may help to explain why the diffusion
      of research results into clinical practice is often disappointingly slow.

PMID- 1983916
TI  - The epidemiology of licit and illicit substance use among high school students in
      Greece.
AB  - Findings on self-reported adolescent licit and illicit substance use are
      presented based on a nationwide 1984 probability sample of 11,058 Greek
      adolescent students ages 14-18 years old. Regular smoking and use of alcohol in
      the 30 days prior to the survey were reported by 22.3 percent and 82.8 percent,
      respectively. Nearly one-third of the students (30.3 percent) reported lifetime
      use of psychotropic drugs without prescription, without ever having used any
      illicit drug. Illicit drug use is less common in Greece than in other European
      and North American countries with a lifetime prevalence rate of 6 percent.
      Regular use of tobacco, alcohol, and illicit drugs was more common in males,
      while unprescribed use of licit psychotropic drugs prevailed in females. Regular
      smoking, drinking, and illicit drug use were associated with urbanization but not
      socioeconomic status. Between 1984 and 1988 in an Athenian subsample of schools
      there was a 20 percent increase in illicit drug use among males. Use of
      psychotropic drugs without prescription decreased much more than use of tobacco
      and alcohol.

PMID- 1983917
TI  - AIDS-related knowledge, sexual behavior, and condom use among men and women in
      Kinshasa, Zaire.
AB  - This study was conducted in 1988 among a random sample of 6,625 men and women of
      reproductive age in all 24 administrative zones of Kinshasa, the capital city of
      Zaire, to determine existing levels of knowledge regarding AIDS (acquired
      immunodeficiency syndrome), sexual behavior, knowledge and use of condoms in
      marital and extramarital relations; perceived risk of AIDS, and attitudes toward
      testing for the human immunodeficiency virus (HIV). Awareness of AIDS is almost
      universal, and the vast majority know the four main modes of transmission. Almost
      half believed in transmission by mosquitoes and in a vaccine or cure for AIDS.
      The majority of male respondents knew of condoms, but negative attitudes toward
      condom use are widespread, and few respondents perceived them to play a central
      role in combatting AIDS.

PMID- 1983918
TI  - The course of the HIV epidemic among intravenous drug users in Amsterdam, The
      Netherlands.
AB  - To determine if behavioral changes in intravenous drug users in Amsterdam have
      retarded the HIV (human immunodeficiency virus) epidemic in this group in recent
      years, we report that: HIV-antibody seroprevalence in annual samples of injectors
      has been constant over the years 1986-89; HIV-antibody incidence in a cohort of
      injectors appears to have decreased from 1986 to 1987 and stabilized after that
      until 1989; acute hepatitis B incidence in all drug users in Amsterdam declined
      rapidly between 1985-89. It is concluded that changes in drug use behavior so far
      appear to have resulted in a stabilization of the epidemic among injectors, at a
      level with a still disturbingly high incidence rate of 5-6 per 100 person-years.

PMID- 1983919
TI  - Does maternal tobacco smoking modify the effect of alcohol on fetal growth?
AB  - Smoking and drinking habits were registered by a self-administered questionnaire
      in 36th week of gestation in 11,698 pregnant women, more than 80 percent of all
      such women in two Danish cities 1984-87. Alcohol consumption of 120 g/week or
      more was associated with a greater reduction in the average birthweight in the
      babies of smokers than of non-smokers (about 40 grams for the non-smokers and
      about 200 grams for the smokers). This is particularly striking considering that
      the average birthweight for smokers is lower than for non-smokers. A birthweight
      difference of more than 500 grams was found between babies of mothers who neither
      smoked nor drank and mothers who smoked and drank heavily. Our data suggest that
      women's smoking habits should be taken into consideration when giving pregnant
      women advice about drinking.

PMID- 1983920
TI  - Admission and mid-stay MedisGroups scores as predictors of death within 30 days
      of hospital admission.
AB  - We examined the ability of MedisGroups, a severity measure based on clinical data
      abstracted from the medical record, to predict mortality 30 days following
      admission. MedisGroups measures severity both on admission and approximately one
      week into the hospital stay. The data base was a random sample of 20,985
      admissions of Medicare beneficiaries with one of six conditions from 833
      hospitals in seven states between January 1985 and May 1986. In all six
      conditions, higher admission and mid-stay severity scores were generally
      associated with higher risk of death. Across the six conditions, the R-squared
      values for predicting death using admission scores ranged from 0.01 to 0.16; R
      squared values using mid-stay scores ranged from 0.03 to 0.34; and R-squared
      values from combining admission and mid-stay scores ranged from 0.05 to 0.41.
      Admission MedisGroups score was thus only modestly predictive of 30-day
      mortality. While the mid-stay score was more powerful, it may not be an
      appropriate severity adjuster to screen for quality using hospital mortality
      rates because it could be influenced by substandard care.

PMID- 1983921
TI  - The impact of HIV-related illness on employment.
AB  - We used structured telephone interviews to determine the extent of work loss
      following onset of symptoms, the interval between onset of symptoms and cessation
      of work, and the risk factors for work loss among 193 persons with symptoms of
      human immunodeficiency virus (HIV)-related illness attending the AIDS Clinic at
      the University of California, San Francisco, between October 1, 1988, and
      September 30, 1989. Estimates of the duration of time between onset of HIV
      related symptoms and work loss derive from the life table method of Kaplan and
      Meier. A Cox proportional hazards model is used to estimate the effect of risk
      factors on the probability of withdrawing from work in each time interval. Eighty
      six percent of the respondents worked prior to onset of the first symptom of HIV
      related illness; 40 percent were working at the time of the most recent
      interview, a mean of 958 days later. The total number of hours worked declined by
      59 percent during this time. Kaplan-Meier analysis indicates that 50 percent who
      worked prior to onset of HIV-related illness stopped working within two years and
      all had stopped within 10 years after onset of the first symptom.

PMID- 1983922
TI  - Reporting of occupational injury and illness in the semiconductor manufacturing
      industry.
AB  - In the United States, occupational illness and injury cases meeting specific
      reporting criteria are recorded on company Occupational Safety and Health
      Administration (OSHA) 200 logs; case description data are submitted to
      participating state agencies for coding and entry in the national Supplementary
      Data System (SDS). We evaluated completeness of reporting (the percentage of
      reportable cases that were recorded in the company OSHA 200 log) in the
      semiconductor manufacturing industry by reviewing company health clinic records
      for 1984 of 10 manufacturing sites of member companies of a national
      semiconductor manufacturing industry trade association. Of 416 randomly selected
      work-related cases, 101 met OSHA reporting criteria. Reporting completeness was
      60 percent and was lowest for occupational illnesses (44 percent). Case
      description data from 150 reported cases were submitted twice to state coding
      personnel to evaluate coding reliability. Reliability was high (kappa 0.82-0.93)
      for "nature," "affected body part," "source," and "type" variables. Coding for
      the SDS appears reliable; reporting completeness may be improved by use of a
      stepwise approach by company personnel responsible for reporting decisions.

PMID- 1983924
TI  - A routine tool for detection and assessment of epidemics of influenza-like
      syndromes in France.
AB  - A regression model for the nonepidemic level of influenza-like syndrome has been
      estimated from the 55,200 cases collected between October 1984 and August 1988
      using the French Communicable Diseases Computer Network. The start of a major
      epidemic in 1988-89 was detected early. The size of the epidemic, for the entire
      country, was estimated at approximately 4.3 million cases. The excess cost of
      sick-leave, among those of working age, was estimated at $86 million.

PMID- 1983923
TI  - Trends in the content and use of oral contraceptives in the United States, 1964
      88.
AB  - Drug marketing and physician survey data were used to examine trends in the use
      and hormonal content of oral contraceptives in the United States between 1964 and
      1988. Retail prescriptions for oral contraceptives peaked at approximately 68
      million in 1973 and have remained between 50 million and 60 million since 1981.
      Despite this relative consistency in the number of prescriptions, physician
      "mentions" of oral contraceptives have increased by approximately 75 percent.
      This increase may reflect closer monitoring of women on oral contraceptives. Use
      of multiphasic formulations has steadily risen, accounting for 37 percent of the
      oral contraceptive prescriptions in 1988. Mean estrogen and progestin doses in
      all types of formulations have steadily declined. A change in the type of
      estrogen and progestin used in preparations has coincided with this decline in
      dose. The association between age and use of high-dose formulations seen in the
      past was no longer evident in 1988. The data demonstrate that oral contraceptive
      formulations in wide use today differ in hormone content from those of the past,
      when most of the major studies addressing the risks associated with oral
      contraceptive use were completed. There is therefore a need to determine the
      risks and long-term effects associated with these newer formulations.

PMID- 1983925
TI  - Antibiotic use among children in an urban Brazilian slum: a risk factor for
      diarrhea?
AB  - Among a cohort of children in a poor urban setting in Brazil, the relative risk
      for the occurrence of a new episode of diarrhea in the two weeks following
      antibiotic use vs all other weeks was 1.44 (95% confidence interval (CI) = 1.33,
      2.45). Among children ever [corrected] exposed to antibiotics, the odds ratio was
      1.34 (95% CI = 0.84, 2.16) after stratifying by individual child and controlling
      for previous diarrhea. Further research is needed to confirm whether antibiotics
      are a risk factor for diarrhea in such settings.

PMID- 1983926
TI  - How satisfying is the practice of internal medicine? A national survey.
AB  - OBJECTIVE: To survey members of the American College of Physicians about their
      level of satisfaction and sources of dissatisfaction with practice, the extent to
      which their satisfaction is reflected in their counseling of students about
      careers in internal medicine, the prevalence of their concerns about patients'
      access to care, and their attitudes toward changes in the health care system.
      DESIGN: A questionnaire survey of a random sample of members of the College.
      PARTICIPANTS: Members (2254) of the College were surveyed; 1446 (64%) responded
      and 1290 (57%) of the responses were usable. MEASUREMENTS AND MAIN RESULTS: More
      than 80% of respondents were satisfied with their relationships with patients,
      professional challenges, and opportunities to interact with colleagues. Only
      about half were satisfied with their potential income, and most were dissatisfied
      with their autonomy or loss of control over clinical decision making. Major
      sources of concern were administrative burdens, the threat of malpractice
      litigation, loss of income, and loss of clinical autonomy. Forty percent of
      internists say that they discourage students from careers in internal medicine,
      and only 39% would once again pursue such a career. "Pain in the practice" seems
      generalized among internists: logistic regression analysis failed to show any
      specific groups who were most dissatisfied or concerned. With regard to access,
      18% of internists had many patients without health care insurance; 69% had some
      patients without coverage; and the majority (61%) had some patients who lost
      their insurance because of changing jobs or location. Assuring universal access
      to care received the highest priority rating of a set of criteria for health care
      reform. CONCLUSIONS: There is growing dissatisfaction with the practice of
      internal medicine, primarily related to concerns over loss of clinical autonomy,
      the increase in administrative burdens, the potential loss of income, and the
      threat of malpractice litigation. Although physicians are concerned about
      patients' access to care, proposals to improve access should be examined for
      their effects on the major sources of physicians' dissatisfaction with practice.

PMID- 1983927
TI  - Medical student attitudes about internal medicine: a study of U.S. medical school
      seniors in 1988.
AB  - OBJECTIVE: To determine the attitudes of medical students toward careers in
      internal medicine. DESIGN: Cross-sectional national survey of U.S. medical school
      seniors. PARTICIPANTS: The 10,379 respondents to the 1988 Medical Student
      Graduation Questionnaire from the Association of American Medical Colleges.
      MEASUREMENTS AND MAIN RESULTS: Most men and women selecting internal medicine (n
      = 1931) as well as those switching from earlier preferences for internal medicine
      (n = 1606) made their final decisions about specialty during the third and fourth
      years of medical school. Almost 50% of students planning to be internists cited
      "intellectual content" as the most important factor in their choice of specialty.
      "Diagnostic challenge" was next most frequently cited. "Type of patient seen" and
      "role models" were more frequently cited as the most important factors in
      specialty choice for all other specialties than for internal medicine. Students
      who switched away from earlier preferences for general internal medicine cited
      the following most important factors in descending order of frequency: "too
      demanding of time and effort," "inconsistent with personality," "negative
      clerkship experiences," "don't like the type of patient," and "specialty chosen
      more fulfilling." The same five factors, in a different order of frequency, were
      given for switching from the subspecialties of internal medicine. CONCLUSIONS:
      Most medical students make their final choices about specialty during or after
      their clerkship year. Knowledge of these students' attitudes toward internal
      medicine could form the basis for the development of strategies to enhance the
      attractiveness of internal medicine among these students while they are making
      their final decisions about specialty.

PMID- 1983929
TI  - Changes in the medical knowledge of candidates for certification.
AB  - PURPOSE: To determine whether the medical knowledge of candidates from different
      types of medical schools changed between 1983 and 1988. SUBJECTS: Candidates for
      certification who took the 1983 to 1988 examinations in internal medicine were
      divided into five groups according to the type and location of the medical school
      they had attended and, in some instances, their citizenship: graduates of U.S.
      medical schools, of Canadian medical schools, and of osteopathic medical schools
      as well as U.S. citizens who graduated from foreign medical schools and non-U.S.
      citizens who graduated from foreign medical schools. DESIGN: Performance on items
      that were common to four pairs of the 1983 to 1988 certifying examinations (1983
      and 1985, 1984 and 1986, 1985 and 1987, and 1986 and 1988) was analyzed. RESULTS:
      The scores of graduates of U.S. medical schools decreased, and the scores of non
      U.S. citizens who graduated from foreign medical schools increased. Trends in the
      performance of graduates of Canadian and osteopathic medical schools and of U.S.
      citizens who graduated from foreign medical schools were not discernible.
      CONCLUSIONS: The cumulative decline in the performance of graduates from U.S.
      medical schools and the progressive improvement in the performance of non-U.S.
      citizens who graduated from foreign medical schools may ultimately manifest
      itself in patient care.

PMID- 1983928
TI  - A national study of AIDS and residency training: experiences, concerns, and
      consequences.
AB  - OBJECTIVE: To examine residents' experiences in the care of patients with the
      acquired immunodeficiency syndrome (AIDS), and to examine factors that may
      influence their attitudes about such care. DESIGN: Cross-sectional, self
      administered questionnaire survey conducted in 1989. PARTICIPANTS: All senior
      internal medicine and family medicine residents in ten geographically
      representative states who were identified through the 1986 National Residency
      Matching Program. MEASUREMENTS AND MAIN RESULTS: Seventy-four percent of
      residents reported that patients with AIDS accounted for 5% or more of general
      medicine admissions, and 50% of residents reported that they were currently
      following one or more human immunodeficiency virus (HIV)-infected patients in
      their continuity clinics. Among residents who had provided ambulatory care to
      patients with AIDS, 77% felt that it was an excellent educational experience, and
      among those who planned to do general primary care in their future practices, 74%
      planned on providing primary care to patients with AIDS. However, 61% expressed
      concerns about the adequacy of their training in AIDS ambulatory care. A greater
      amount of contact with outpatients who had AIDS, but not with inpatients who had
      AIDS, was associated with residents' intending to provide AIDS primary care in
      their future practices. Among all residents, 23% reported that, if given a
      choice, they would not provide care to any patients with AIDS, and 23% reported
      that they would not work in an area with a high prevalence of AIDS because of
      concern about contracting the syndrome. Nine percent of residents reported that
      they had been exposed to a blood-contaminated needlestick from an HIV
      seropositive patient. CONCLUSIONS: Although most residents have substantial
      contact with inpatients and outpatients with AIDS, most still find their
      education in AIDS ambulatory care to be deficient. A minority of residents would
      prefer not to care for patients with AIDS. Residency curricula should include
      training and experience in ambulatory AIDS care, explicitly address negative
      attitudes toward caring for patients with AIDS, and include programs to reduce
      needlestick exposures.

PMID- 1983930
TI  - National Study of Internal Medicine Manpower. XVIII: Subspecialty fellowships
      with a special look at hematology and oncology, 1988-1989.
AB  - OBJECTIVE: To determine the number and distribution of internists in subspecialty
      training and compare with data collected since 1976; to determine the
      distribution of activity of subspecialty fellows; and to focus on hematology and
      oncology. DESIGN: Repeated mail survey with telephone follow-up. PARTICIPANTS:
      All directors of subspecialty training programs in internal medicine in the
      United States. RESULTS: The 1988-1989 census identified 7530 fellows in training,
      55 more than in 1987-1988. There are 24 more first-year fellows. Reports on the
      activities of subspecialty fellows show that, overall, 53% of fellows' time is
      spent in direct patient care, 20% on basic research, 15% on patient-related
      research, and 12% in teaching. CONCLUSIONS: The number of internists entering
      subspecialty training has risen at a considerably slower rate in the last 5 years
      compared with the 5 years before that. The length of subspecialty training has
      increased significantly since 1976. There has been a shift in subspecialty choice
      from hematology to oncology and toward joint programs offering both
      subspecialties.

PMID- 1983931
TI  - Parental leave policies for faculty in U.S. medical schools.
AB  - OBJECTIVE: To assess medical school policies for maternity and other parental
      leaves as well as related opportunities for part-time employment, flexibility in
      tenure systems, and the availability of child care centers. DESIGN: Cross
      sectional survey of all 127 U.S. medical schools based on telephone interviews
      and review of faculty handbooks. MEASUREMENTS AND MAIN RESULTS: Ninety-three
      percent of medical schools responded. Twenty-two percent of medical schools have
      no written guidelines for maternity leave, 45% categorize maternity leave as a
      form of sick or disability leave, and only 34% have developed specific policies.
      Most schools (61%) require that maternity leave be taken from allotted sick days
      or from vacation days (or from both) for women to obtain salary support. The time
      available from sick and vacation leave averages 6.8 weeks. Although 72% of
      schools make allowances in the tenure probationary period for extended leaves of
      absence, few have developed specific provisions for childbearing or childrearing.
      Finally, 18% of medical schools have child care facilities. CONCLUSIONS:
      Considerable work is needed to develop adequate support for faculty members who
      are parents. Recommendations include developing specific parental leave policies
      and flexible tenure systems and providing adequate child care facilities.

PMID- 1983932
TI  - Internists' practices in health promotion and disease prevention. A survey.
AB  - OBJECTIVE: To estimate internists' use of disease prevention and health promotion
      activities, and to explore demographic, professional, behavioral, psychological,
      cognitive, and organizational factors associated with the use of such practices.
      DESIGN: Mail survey. SETTING AND SUBJECTS: A sample of 2610 members and fellows
      of the American College of Physicians (ACP) participated in the study. They
      engaged in patient care activities more than 20 hours per week and were
      stratified by gender and region. They lived in four geographic areas of the
      United States (Northeast, Southeast, Central, and West), comprising 21 ACP
      regions. MEASUREMENTS: A questionnaire requesting background information as well
      as information about personal health; record keeping; use of immunizations
      (pneumococcal, influenza, tetanus, hepatitis B); use of screening tests and
      procedures for detecting cancer (breast examination, Papanicolaou smear, stool
      occult blood test) and other diseases (electrocardiograms, cholesterol level
      tests, chest radiographs); and behavioral counseling to promote health (in the
      areas of smoking, exercise, and alcohol and seat belt use). MAIN RESULTS:
      Internists used effective preventive interventions less frequently and
      ineffective practices more frequently than experts recommend. Internists' use of
      health promotion and disease prevention activities is associated with habit,
      attitude, and a lack of adequate knowledge. Younger physician age, general
      internal medicine practice, and personal health promotion and disease prevention
      practices were strongly associated with more appropriate use of recommended
      practices (P less than 0.01). CONCLUSIONS: Internists' use of disease prevention
      and health promotion activities falls short of expert recommendations. Programs
      to improve the delivery of preventive services might be aimed at improving
      physicians' personal health practices, might be directed toward patients, and
      might include the development of effective systems to remind physicians.

PMID- 1983933
TI  - The counseling practices of internists.
AB  - OBJECTIVES: To determine the counseling practices of a group of internists in the
      areas of smoking, exercise, and alcohol and seat belt use, and to determine the
      associations among physicians' personal health habits and their counseling
      practices. DESIGN: A random stratified sample of members and fellows of the
      American College of Physicians in 21 regions selected to represent all areas of
      the United States. Because of the relatively small proportion of women in this
      group, they were oversampled. SETTING: Physicians' practices. PARTICIPANTS: One
      thousand three hundred and forty-nine internists (members or fellows of the
      College) returned questionnaires, for a response rate of 75%; 52% defined
      themselves as general internists. INTERVENTIONS: A questionnaire was used to
      obtain information on internists' use of cigarettes, alcohol, and seat belts and
      their level of physical activity. Data were obtained on the indications used for
      counseling and the aggressiveness of counseling about each of these four habits.
      MEASUREMENTS AND MAIN RESULTS: Bivariate and logistic regression analyses were
      used to compare the tendencies of internist subgroups both in using various
      indications for counseling and in the thoroughness of counseling. Generalists
      were more likely than specialists to counsel at least once all patients who were
      at risk and to be more aggressive in counseling. Ninety percent of respondents
      counseled all of their patients who smoked, but 64.5% never discussed the use of
      seat belts. Only 3.8% of these internists currently smoked cigarettes, 11.3%
      drank alcohol daily, 38.7% were extremely or quite active, and 87.3% used seat
      belts all or most of the time. Among men internists, for every habit except
      alcohol use, personal health practices were substantially associated with
      counseling patients; for example, nonsmoking internists were more likely to
      counsel smokers, and very physically active internists were more likely to
      counsel about exercise. Among women internists, being very physically active was
      associated with counseling more patients about exercise and alcohol use.
      CONCLUSIONS: The low level of self-reported counseling among these internists
      suggests that further emphasis on training in these skills is needed. The
      association between personal and professional practices suggests that medical
      schools and housestaff training programs should support health promotion
      activities for future internists.

PMID- 1983934
TI  - Time-limited certification and recertification: the program of the American Board
      of Internal Medicine. The Task Force on Recertification.

PMID- 1983935
TI  - Medical student interest in internal medicine. Initial report of the Society of
      General Internal Medicine Interest Group Survey on Factors Influencing Career
      Choice in Internal Medicine.
AB  - OBJECTIVE: To determine the factors that attract students toward and push
      students away from a career in internal medicine. DESIGN: National survey of
      senior U.S. medical students using a stratified random cluster sampling of
      medical schools. PARTICIPANTS: The survey included 1650 U.S. senior students from
      16 medical schools, of whom 1244 (76%) responded. MEASUREMENTS AND MAIN RESULTS:
      A survey instrument was developed and pilot tested at 17 medical schools. Twenty
      four percent of the respondents to the final survey chose a career in general
      internal medicine (9%) or subspecialty internal medicine (15%). A career in
      internal medicine had been "seriously considered" by 608 respondents (50%) who
      finally chose a career other than internal medicine (the "switchers"). Compared
      with other specialties, internal medicine was perceived as being more stressful
      to residents, more demanding of time and workload as a career and a residency,
      and as an easier residency to enter. Internal medicine was also seen as providing
      less satisfaction for residents, having lower income potential, and allowing less
      leisure time. For the 608 switchers, the most important influences leading to
      their decision to switch were the type of patient seen in internal medicine (for
      example, chronically ill, alcohol and drug abusing patients) as well as
      dissatisfaction and stress among internal medicine residents. Factor analysis
      showed that three factors, "intellectual challenge of internal medicine,"
      "primary care interests," and "the medicine clerkship" attracted students toward
      internal medicine, whereas three others, "taking care of chronically ill
      patients," "level of satisfaction among internists and medical residents," and
      "workload and stress" pushed students away from internal medicine. Factors
      pushing students away from internal medicine were significantly more negative
      with regard to a career in general as opposed to subspecialty internal medicine
      (P less than 0.001). CONCLUSION: Medical students have serious reservations about
      internal medicine as a career choice. Perceptions about the medical residency,
      the patients they expect to see, and the dissatisfaction among residents and
      internists are foremost in their thinking. Changes to improve the attractiveness
      of internal medicine should address these adverse perceptions while building on
      the positive influences identified by the respondents.

PMID- 1983936
TI  - Promotion and tenure of women and minorities on medical school faculties. The
      American College of Physicians.

PMID- 1983937
TI  - The leadership crisis in internal medicine: what can be done?
AB  - During the 1990s, internal medicine will change. Whether that change will be in
      directions desired by internists will depend on whether effective leadership of
      the discipline is accepted by the academic department chairs. Individually, and
      as a group, they are the only ones with sufficient authority to take control and
      initiate and sustain needed change. The time frame for action is short and
      diminishing. Opportunities still exist for effective leadership to present the
      discipline as more attractive to students by demonstrating that they can play an
      important role in helping to solve problems in health care. Unmet societal needs
      underlie much of the public's disaffection with the profession, and the
      chairpersons must begin to solve those needs. Today's practice environment is
      ever less appealing with increasing regulation and intrusive third-party actions.
      These stresses will increase until internists understand from research the value
      of what they do in practice and learn to choose what is effective in outcome and
      cost. Practice models integrating the skills and talents of internists, as these
      are focused on the needs of patients, are experiments that can be started in
      academic departments. Initiatives for such changes depend on active leadership-
      now sorely lacking in internal medicine.

PMID- 1983938
TI  - Subspecialists and internal medicine: a perspective.
AB  - There is a growing schism between general internal medicine and the medical
      subspecialties. The latter are functioning increasingly as categorical disease
      centers, such as cardiac or cancer centers, which involve subspecialists from
      several departments. These new "horizontal" organizational units are thought to
      enhance the effectiveness of patient care as well as the generation of resources,
      especially for research and training. However, subspecialists operating outside
      of the framework of training, accreditation, and standards established by
      internal medicine are at risk for being less effective in dealing with the
      "whole" patient. Further, the critical evaluation of clinical practices of
      subspecialists is greatly needed and is far more likely to be accomplished
      effectively within departments of internal medicine than in categorical disease
      centers. Therefore, although some strengthening of the new horizontal
      organizational units now seems appropriate, this process must not be allowed to
      erode the important integrating structure provided by internal medicine.

PMID- 1983939
TI  - Grand cru versus generic: different approaches to altering the ratio of general
      internists to subspecialists.
AB  - In the last decade internal medicine has become a less popular career choice
      among medical school graduates. In addition, there has been an increase in the
      percentage of internal medicine residents choosing subspecialty training. The
      factors that have led to the change in the ratio of subspecialists to general
      internists are discussed, and a plan is proposed that would make the practice of
      general internal medicine more attractive and reduce the number of subspecialty
      training positions in the United States.

PMID- 1983940
TI  - Just beyond the next bend in the river: reflections on a medical career.

PMID- 1983942
TI  - A perspective on medical student education for internal medicine.

PMID- 1983941
TI  - The future of internal medicine: framing the questions.

PMID- 1983943
TI  - Professionalism in residency.

PMID- 1983944
TI  - Internal medicine: a view from the country.

PMID- 1983945
TI  - Switching phlebotomy needles.

PMID- 1983946
TI  - Nocturnal hypertension in patients receiving chronic hemodialysis.

PMID- 1983947
TI  - Metoprolol-induced polymyalgia-like syndrome.

PMID- 1983948
TI  - Topical tretinoin and vaginal bleeding.

PMID- 1983949
TI  - White hand: Raynaud phenomenon or leprosy?

PMID- 1983950
TI  - The bookie, the girlfriend, and the vultures.

PMID- 1983951
TI  - Advances in dermabrasion.

PMID- 1983952
TI  - Fibrosing conditions in childhood.

PMID- 1983953
TI  - Childhood histiocytosis syndromes.

PMID- 1983954
TI  - Cutaneous manifestations of immunological disorders in children.

PMID- 1983955
TI  - Personal computers: building better projects in medicine.

PMID- 1983956
TI  - Molecular pathology of collagen in cutaneous diseases.

PMID- 1983957
TI  - Veterinary dermatohistopathology: what's new and exciting?

PMID- 1983958
TI  - Differential diagnosis of panniculitis.

PMID- 1983959
TI  - An appraisal of the dysplastic nevus syndrome concept.

PMID- 1983960
TI  - Dermatology in space: the final frontier.

PMID- 1983961
TI  - Superficial foot and ankle surgery.

PMID- 1983962
TI  - Oxidative stress in mitochondria: its relationship to cellular Ca2+ homeostasis,
      cell death, proliferation, and differentiation.
AB  - A variety of chemically different prooxidants causes Ca2+ release from
      mitochondria. This prooxidant-induced Ca2+ release occurs from intact
      mitochondria via a route which is physiologically relevant and may be regulated
      by protein monoADP-ribosylation. When the released Ca2+ is excessively 'cycled'
      by mitochondria (continuously taken up and released) the inner membrane is
      damaged. This leads to a decreased ability of mitochondria to retain Ca2+,
      uncoupling of mitochondria, and an impairment of ATP synthesis, which in turn
      deprives the cell of the energy necessary for the proper functioning of the Ca2+
      ATPases of the endoplasmic (sarcoplasmic) reticulum, the nucleus and the plasma
      membrane. The ensuing rise of the cytosolic Ca2+ level cannot be counterbalanced
      by the damaged mitochondria which, under normoxic conditions, act as a safety
      device against an increase of the cytosolic Ca2+ concentration. The impaired
      ability of mitochondria to retain Ca2+ may lead to cell death. However, there is
      also evidence emerging that release of Ca2+ from mitochondria may be
      physiologically important for cell proliferation and differentiation.

PMID- 1983963
TI  - Viscometry of alkaline cell lysates--the hitherto simplest short-term test for
      chromatin-interactive agents? Investigations in rat thymic and splenic cells.
AB  - Alkaline (AL) lysates from thymic cells (T-cells) and splenic cells (S-cells) of
      the rat were measured by low-shearing glass capillary viscometry. AL-viscometry
      was compared to the nucleoid sedimentation technique and the alkaline unwinding
      method. The results obtained in cells treated by (a) DNA strand breaking agents
      (X-rays, UV-light, doxorubicin, bleomycin, hydrogenperoxide,
      methylmethanesulfonate (MMS)), (b) intercalating and/or cross-linking substances
      (ethidium bromide, actinomycin D, mitomycin C, bisbenzimide), (c) the DNA repair
      inhibitor 3-aminobenzamide (3-AB) and (d) hyperthermia suggest that AL-viscometry
      may be considered as a very simple, rapid and inexpensive preliminary short-term
      test for detecting chromatin-interactive agents. Whereas agent- and cell-specific
      characteristics can be also revealed by AL-viscometry, quantification of specific
      lesions and conclusions as to the mechanisms of action require additional assays.

PMID- 1983964
TI  - 32P-postlabeling of N-7, N2 and O6 2'-deoxyguanosine 3'-monophosphate adducts of
      styrene oxide.
AB  - Adducts were prepared by reacting styrene oxide with 2-deoxyguanosine 3'
      monophosphate (dGMP). Four isomeric N-7-, two diastereomeric N2- and three
      isomeric O6-adduct were isolated and characterized. The adducts were used as
      substrates in the 32P-postlabeling reaction. No phosphorylation products were
      seen with the N-7-alkylation products. One diastereomeric N2-adduct was labeled
      with 20% efficiency and the second with a markedly lower efficiency. Two of the
      three O6-adducts were labeled with 5% and the third with 10% labeling efficiency.
      The results suggest that large N-7-dGMP adducts are very poor substrates of T4
      polynucleotide kinase. The diastereomeric products are labeled at different
      efficiencies indicating stereoselectivity in the kinase reaction.

PMID- 1983965
TI  - Metabolic denitrosation of N-nitroso-N-methylaniline: detection of amine
      metabolites.
AB  - The enzymatic denitrosation of N-nitroso-N-methylaniline (NMA) was investigated
      by measuring the resulting amine metabolites when NMA was incubated with liver
      microsomes of PB-pretreated mice. Aniline was found to be the main amine
      metabolite. Small amounts of the secondary amine, N-methylaniline (MA) and its
      metabolite, p-methylaminophenol (p-MAP), could also be detected. Incubation of MA
      resulted in the formation of aniline and p-MAP. The velocity of the metabolism of
      MA was somewhat faster than that of NMA. On the basis of the measured Vmax values
      the formation of aniline from MA or from NMA proceeded at nearly identical rates.
      The dissociation constants as a measure of binding affinity to cytochrome (cyt.)
      P-450 were determined by measuring the binding spectra. NMA has one Ks of 3.1 mM,
      whereas MA shows two apparent Ks values, 650 microM and 25 mM, respectively. The
      results are discussed in relation to the enzymatic mechanism of denitrosation of
      NMA.

PMID- 1983966
TI  - Fc-receptor-mediated phagocytosis: abnormalities associated with diabetes
      mellitus.
AB  - The family of Fc receptors (FcR) for IgG play pivotal roles in affector,
      effector, and regulatory functions of cells of the immune system. Thus, changes
      in expression and activation of FcRs may contribute to a variety of disease
      manifestations that are the consequence of abnormalities in immune system
      function. Patients with diabetes mellitus are often plagued with recurrent
      bacterial and mycotic infections, as well as large and small vessel injury which
      may in part be immune mediated and which lead to organ dysfunction. Hormone
      mediated changes in immune system function have been postulated to contribute to
      a variety of the complications experienced by patients with diabetes mellitus. It
      is the purpose of this review to summarize current knowledge regarding
      abnormalities in immune system function in diabetes mellitus with special
      emphasis on classical hormonal modulation of Fc receptor-mediated phagocytosis.

PMID- 1983967
TI  - Characterization of autoantibodies to the CD4 molecule in human immunodeficiency
      virus infection.
AB  - Autoantibodies to the CD4 protein, which serves as a receptor for the human
      immunodeficiency virus (HIV) on the surface of target cells, were found in
      patients with different stages of HIV disease. Using recombinant soluble CD4
      (rCD4) antigen in a enzyme-linked immunosorbent assay (ELISA), we detected serum
      anti-CD4 antibodies in approximately 20% of HIV-1 infected patients and 13% of
      HIV-2 infected patients. There was no correlation between the presence of anti
      CD4 antibodies and the stage of HIV disease, serum IgG concentration, number of
      peripheral blood CD4 positive lymphocytes, or CD4/CD8 lymphocyte ratios in HIV-1
      infected patients. Immunoaffinity purified anti-CD4 antibody failed to bind to
      CD4 positive cells using flow cytometric analysis. However, this antibody could
      weakly bind to CD4 positive cells that had been preincubated with purified
      recombinant gp120 (rgp120). In addition, using an ELISA system, we found that the
      binding of purified patient anti-CD4 antibody to rCD4 was increased in the
      presence of rgp120. Similar increased binding was observed with the anti-CD4
      monoclonal antibody OKT4, but not with anti-Leu3a. These data suggest that a
      conformational change in the C-terminal domains of CD4 may be induced by gp120
      binding and could lead to development of anti-CD4 antibodies.

PMID- 1983968
TI  - Conserved T cell receptor V gene usage by uveitogenic T cells.
AB  - Retinal S-antigen is widely used to study the LEW rat model of experimental
      autoimmune uveoretinitis (EAU). In this report, we have examined the T cell
      receptor V gene usage of several T cell lines recognizing either pathogenic or
      nonpathogenic sites on S-antigen to determine whether the V alpha 510 and V beta
      510 rat homologues of the murine V alpha 2 and V beta 8 families, respectively,
      are used by uveitogenic T cells. Using cDNA probes for a LEW rat T cell receptor
      specific for the encephalitogenic determinant of myelin basic protein, we have
      found that in the retinal S-antigen/EAU model for autoimmune disease,
      pathogenicity correlates with usage of those rat V genes. Thus, all of the
      pathogenic lines were found to express T cell receptors of the V beta 510 and V
      alpha 510 families; conversely, V beta 510 usage was not detected in any of the
      nonpathogenic lines. Usage of these V regions has been associated with
      pathogenicity in the murine and rat models of experimental autoimmune
      encephalomyelitis, and now with S-antigen-induced EAU.

PMID- 1983969
TI  - B cells in autoimmune (NZB x NZW)F1 mice show altered IgG isotype switching upon
      T cell-dependent antigenic stimulation in vitro.
AB  - Humoral immune responses of (NZB x NZW)F1 (BWF1) autoimmune mice to T cell
      dependent antigens often exhibit a predominance of IgG2 antibodies, while normal
      mice produce IgG1 antibodies. In order to determine whether this results from
      differences in properties of the B cells or the T cells involved, the responses
      of both primary and secondary BWF1 B cells to the antigen DNP-hemocyanin (Hy)
      were measured in limiting dilution splenic fragment cultures in the presence of
      normal T cell help. Furthermore, the capacity of Hy-primed lymph node T cells
      from BWF1 mice to provide help to BALB/c nu/nu B cells was determined in modified
      splenic fragment cultures. These experiments indicated that (a) stimulation of
      primary BWF1 B cells with DNP-Hy and normal T cell help failed to yield
      significant numbers of clones which produced any of the IgG isotypes; (b)
      antigenic stimulation of BWF1 secondary B cell clones also demonstrated a paucity
      of IgG1, but elevated production of IgG2 isotypes; and (c) Hy-primed BWF1 lymph
      node T cells were comparable to those derived from BALB/c mice in their capacity
      to provide both help for nu/nu B cell responses and modulation of IgG isotype
      switching. BWF1 B cells apparently differ from normal murine B cells in their
      capacity to produce IgG antibodies upon T cell-dependent antigenic stimulation.

PMID- 1983970
TI  - The paradoxical effects of diethyldithiocarbamate: comparisons between New
      Zealand black/white F1 hybrid and Balb/c mice.
AB  - Diethyldithiocarbamate (DTC), an immunomodulative agent suggested to enhance T
      cells, has been shown to prolong life in autoimmune MRL-lpr/lpr mice. In addition
      to increased survival, MRL-lpr/lpr mice treated with DTC displayed a number of
      changes in expression of cell surface antigens as well as decreased serum
      autoantibody levels. To determine if DTC treatment would have similar positive
      effects on another murine model of autoimmune disease, we studied the New Zealand
      Black/White F1 hybrid (NZB/W). In addition, the effects of DTC treatment on cell
      surface antigen expression were compared between the NZB/W and a normal murine
      strain, the Balb/c. DTC treatment increased the density of cell surface antigens
      in the NZB/W, but decreased the density of these antigens in the Balb/c.
      Treatment with DTC induced distinct changes in the percentage of cells expressing
      specific surface antigens that differed between the NZB/W and the Balb/c. There
      was no affect on serum anti-DNA and anti-histone antibody levels or on survival
      in NZB/W mice treated with DTC. Therefore, while DTC treatment did not
      successfully influence the disease course in the NZB/W, it did result in specific
      changes in cell surface antigens. These data demonstrate that DTC is capable of
      inducing a variety of immunologic changes depending upon the strain treated.

PMID- 1983971
TI  - Capacity of tumor necrosis factor to augment lymphocyte-mediated tumor cell lysis
      of malignant mesothelioma.
AB  - Recombinant human tumor necrosis factor (rHuTNF) was evaluated both for direct
      anti-tumor action against human malignant mesothelioma and for its capacity to
      augment the generation and lytic phases of lymphocyte-mediated cytotoxicity
      against this tumor. rHuTNF was directly toxic by MTT assay to one of two
      mesothelioma cell lines evaluated, but had no effect on susceptibility to
      subsequent lymphocyte-mediated lysis of either line. TNF alone was incapable of
      generating anti-mesothelioma lymphokine-activated killer cell (LAK) activity.
      Furthermore, it did not augment the degree or LAK activity produced by submaximal
      interleukin-2 (IL-2) concentrations nor did it augment lysis of mesothelioma
      cells by natural killer (NK) or LAK effector cells during the 4-hr 51chromium
      release cytolytic reaction. The studies also suggest that mesothelioma targets
      are less responsive to TNF plus submaximal IL-2 concentrations than the standard
      LAK sensitive target Daudi, raising the possibility that intermediate LAK
      sensitive tumors such as mesothelioma may require separate and specific
      evaluation in immunomodulation studies. This in vitro study indicates that use of
      low-dose rHuTNF and IL-2 is unlikely to be an effective substitute for high-dose
      IL-2 in generation and maintenance of LAK activity in adoptive immunotherapy for
      mesothelioma.

PMID- 1983972
TI  - Familial selective IgA deficiency with circulating anti-IgA antibodies: a
      distinct group of patients?
AB  - Two families were investigated in which the mothers had selective IgA deficiency
      and circulating class-specific anti-IgA antibodies. Both gave birth to two
      children who were found to be IgA deficient. Three of these children developed
      anti-IgA antibodies before puberty. In vitro immunoglobulin production studies
      performed in the children of both families revealed an IgA B cell defect combined
      with IgA-specific excessive T suppressor function in all four. The mechanisms by
      which transplacental passage of maternal anti-IgA antibodies could have
      interfered with the developing IgA system in the offspring are discussed.

PMID- 1983973
TI  - The Goiania radiation accident.

PMID- 1983974
TI  - The Goiania radiation accident.

PMID- 1983975
TI  - Medical and related aspects of the Goiania accident: an overview.
AB  - On 13 September 1987, a radiation accident occurred in the city of Goiania in
      Central Brazil. Approximately 250 people were exposed to a 137Cs source from an
      abandoned radiotherapy unit. At least 14 patients showed some degree of bone
      marrow depression, and eight developed the classical signs and symptoms of acute
      radiation syndrome (ARS). Twenty-eight people presented local radiation injuries
      ranging from first to third degree, and 104 individuals showed evidence of
      internal contamination. This paper describes the circumstances of the event, the
      first-aid measures taken, the criteria adopted for triage of the exposed
      population, and the radiation protection procedures used during the clinical
      management of the irradiated individuals.

PMID- 1983976
TI  - Localized lesions induced by 137Cs during the Goiania accident.
AB  - A description is given of initial symptoms and clinical observations regarding
      acute localized radiation lesions in 28 persons exposed to 137Cs during the
      Goiania radiological accident. Specialized procedures to estimate the extent and
      gravity of the lesions and establish a therapeutic strategy, as well as to
      anticipate the prognosis in each case, are briefly discussed. Measures taken for
      reduction of pain and inflammation are noted, and an explanation is given for
      difficulties encountered due to adverse working conditions and the serious
      clinical manifestations presented by various patients concomitantly with their
      lesions. Also noted is the difficulty in obtaining credible information regarding
      exposure, such as source-to-object distance, duration of exposure, and source
      activity, which precluded dosimetry studies in most cases.

PMID- 1983977
TI  - Personal insights into the Goiania radiation accident.

PMID- 1983978
TI  - Clinical and hematological aspects of 137Cs: the Goiania radiation accident.
AB  - Fifty persons involved in the 137Cs accident in Goiania showed symptoms of whole
      body and local acute irradiation and also external or internal contamination
      mainly due to ingestion or absorption of 137Cs. Fourteen of the 50 developed
      severe bone marrow depression characterized by neutropenia and thrombocytopenia.
      Eight of these 14 received GM-CSF intravenously. None were submitted to bone
      marrow transplantation. Four of the 14 died due to hemorrhage and infection. For
      those with significant internal contamination evaluated by in-vitro and in-vivo
      assays, Prussian Blue was administered with doses ranging from 1.5 to 10 g d-1.
      Besides Prussian Blue, other measures were taken to increase decorporation of
      137Cs, including administration of diuretics, water overload, and ergometric
      exercises. From 50 to 100 persons are being followed in a medical protocol.

PMID- 1983979
TI  - Measurements of 137Cs in blood from individuals exposed during the Goiania
      accident.
AB  - Blood samples of some highly internally contaminated Goianian patients were
      measured for 137Cs activity. The distribution of activity among the blood
      components was checked. We found that the majority of the activity was confined
      to the cellular fraction, mainly to the erythrocytes (red cells).

PMID- 1983980
TI  - Application of in-vitro bioassay for 137Cs during the emergency phase of the
      Goiania accident.
AB  - In the Goiania accident, many individuals suffered external and internal
      contamination. The screening of internal contamination was done through 137Cs
      urinary excretion. During the first month after the accident, only in-vitro
      bioassay procedures were done. Incorporation into the body and committed doses
      were estimated using age-specific mathematical models correlating these
      quantities to the 137Cs excreted in urine. The ratio of feces to urine of 137Cs
      excretion was used to evaluate the effectiveness of the administration of
      Prussian Blue on removal of 137Cs from the body.

PMID- 1983981
TI  - The Goiania accident: behind the scenes.

PMID- 1983982
TI  - Design and operation of a whole-body monitoring system for the Goiania radiation
      accident.
AB  - With as many individuals involved in the Goiania 137Cs accident who had high
      levels of internal contamination, it was necessary to improvise a whole-body
      counter installation in loco. The in-vivo counting system was located in a 4.0 X
      3.5 X 3.5-m room, where seven layers of 2-mm lead sheets with dimensions of 2.0 m
      X 1.0 m were overlaid on the floor at loci that were equidistant from the walls.
      A 20-cm diameter NaI (Tl) detector was installed at a height of 2.05 m above the
      floor at the center of the room. The detector was shielded and collimated with 5
      cm of lead. The enormous amounts of activity in the subjects required the
      detector to be positioned at a height of 2.05 m. Subjects were required to wear
      disposable clothing and lie on a reclining, fiberglass chair. Counting time for
      the subjects was 2 min (live-time). The minimum detectable 137Cs activity for
      this counting time was 7.3 kBq* (0.05 significance level). Besides the accident
      victims, all individuals who had direct or indirect contact with contaminated
      people or areas were also monitored. More than 300 people of both sexes, with
      ages varying from a few months to 72 y, were measured for whole-body
      radioactivity. The observed activities ranged from less than the minimum
      detectable activity (MDA) to 59 MBq.

PMID- 1983983
TI  - Studies of Cs retention in the human body related to body parameters and Prussian
      blue administration.
AB  - Using the in-vivo monitoring data from the individuals that suffered internal
      contamination in the Goiania accident, a preliminary study on the elimination of
      Cs from their body was conducted. It was concluded that elimination follows a
      first-order linear kinetic pattern, both with and without Prussian Blue
      treatment. Cesium half-lives for both sexes were shown to be influenced mainly by
      the weight of each individual. In general, Prussian Blue seems to reduce the half
      life by 32%. At the time our study was conducted, patients who were under
      treatment with the drug were receiving 3 g d-1, 6 g d-1, or 10 g d-1 of the
      medication. Our results suggest that there is an optimum dosage for a certain
      weight range to achieve this reduction in half-life, but one would need more data
      to statistically prove this assumption.

PMID- 1983984
TI  - Medical aspects of 137Cs decorporation: the Goiania radiological accident.
AB  - In September 1987, the Goiania radiological accident involving a source of 137Cs
      culminated in about 140 victims who presented internal and/or external
      contamination and/or external exposure to radiation and/or radiation burns.
      Internal contamination was verified through analysis of urine and fecal samples.
      Internal contamination was also evaluated by measurements performed at the whole
      body counter installed in Goiania in November 1987. To enhance the decorporation
      of 137Cs, patients were treated with the following: 1) Prussian Blue, oral
      administration, in 46 patients; 2) diuretics, oral administration, in 17
      patients; 3) induced perspiration, increasing 137Cs elimination. These procedures
      were done under rigorous clinical evaluation and considering the data from assay
      of excreta and data obtained from the whole-body counter. The doses of Prussian
      Blue exceeded about 6.5 times the dose previously indicated in the literature. It
      was the first time diuretics were used in humans to treat 137Cs internal
      contamination. The results of these procedures are discussed.

PMID- 1983985
TI  - The fate of chromosomal aberrations in 137Cs-exposed individuals in the Goiania
      radiation accident.
AB  - Following the Goiania radiation accident, lymphocytes from 110 exposed or
      potentially exposed individuals were analyzed for the frequencies of chromosomal
      aberrations (dicentrics and centric rings) to estimate absorbed radiation dose.
      Dose estimates for 21 subjects exceeded 1.0 Gy, and for eight subjects they
      exceeded 4.0 Gy. Four of the subjects died. After the emergency period, a
      cytogenetic follow-up of 10 of the highest exposed patients was started. The
      results suggest that the average disappearance half-time of lymphocytes
      containing dicentric and centric rings was 130 d, which is shorter than the
      usually accepted value of 3 y reported in the literature.

PMID- 1983987
TI  - Novel biodosimetry methods applied to victims of the Goiania accident.
AB  - Two biodosimetric methods under development at the Lawrence Livermore National
      Laboratory were applied to five persons accidentally exposed to a 137Cs source in
      Goiania, Brazil. The methods used were somatic "null" mutations at the
      glycophorin A locus detected as missing proteins on the surface of blood
      erythrocytes and chromosome translocations in blood lymphocytes detected using
      fluorescence in-situ hybridization. Biodosimetric results obtained approximately
      1 y after the accident using these new and largely unvalidated methods are in
      general agreement with results obtained immediately after the accident using
      dicentric chromosome aberrations. Additional follow-up of Goiania accident
      victims will 1) help provide the information needed to validate these new methods
      for use in biodosimetry and 2) provide independent estimates of dose.

PMID- 1983986
TI  - The radiological accident in Goiania: the initial remedial actions.
AB  - The removal of a 50.9-TBq 137Cs source from a radiation therapy facility in
      Goiania gave rise to a radiological accident in September 1987 whose proportions
      were aggravated by the 16-d interval from the beginning of a series of acts that
      resulted in the contamination of people and areas, to the moment of
      identification and seeking of aid. Data gathered from the declarations of persons
      involved in the accident, matched with the medical assessment and radiation
      monitoring of areas affected, made it possible to determine procedures for care
      of victims and for decontaminating operations of these areas. The priorities of
      these procedures were to provide care to victims and eliminate critical paths by
      which other persons might be affected by exposure to radiation or contamination.
      This paper presents (1) remedial actions taken during the first weeks, (2)
      management problems associated with the accident, and (3) lessons learned from
      this episode that are of benefit to us and, hopefully, to others.

PMID- 1983988
TI  - Guidance for selecting nuclear instrumentation derived from experience in the
      Goiania accident.
AB  - Selecting equipment to be used in emergencies is not a simple task. In the
      radiological accident that occurred in Goiania, a large variety of instruments
      from different manufacturers were used, and we observed some of their limitations
      and advantages. This work presents, in a condensed form, the major problems that
      occurred with the equipment used in Goiania and practical observations that could
      be helpful for instrument selection.

PMID- 1983989
TI  - Radiological survey of Goiania by a mobile monitoring unit.
AB  - In September 1987, a 137Cs teletherapy source was ruptured in Goiania and
      environmental consequences ensued. After the initial response to this accident, a
      radiological survey throughout the city was performed using a mobile unit. This
      unit was equipped with two Geiger-Muller detectors outside the vehicle and one
      102 X 102 mm NaI(Tl) detector connected to a dual recorder. All three detectors
      were placed 1 m above ground. The survey system covered a wide range of exposure
      rates, from environmental levels [typically 3.9 X 10(-10) C kg-1 h-1 (15 X 10(-6)
      R h-1) in Goiania] up to 2.6 X 10(-3) C kg-1 h-1 (10 R h-1). Eighty percent of
      the Goiania urban area was covered by this survey, and except for some specific
      locations, the contamination was restricted to the main foci surroundings
      occurring in a nonhomogeneous pattern. The highest value observed in the city
      after the main foci decontamination was 1.8 X 10(-7) C kg-1 h-1 (0.7 mR h-1) in
      the 57th Street area where the source was originally opened. The system, designed
      to perform the survey in the city, played a fundamental role during the
      decontamination process.

PMID- 1983990
TI  - Considerations related to the decontamination of houses in Goiania: limitations
      and implications.
AB  - We are considering some aspects related to the decontamination activities of
      about 50 houses affected by 137Cs in Goiania. We describe the way these
      contaminations occurred, the instruments used, and the procedures. We also
      discuss the dose limits established for decontamination and the consequences
      resulting from this action. We call attention to the importance of not only the
      technical aspects in such activities but also the psychosocial implications
      resulting from them.

PMID- 1983991
TI  - Distribution of 137Cs in soils due to the Goiania accident and decisions for
      remedial action during the recovery phase.
AB  - In September 1987, a powder radioactive source was removed from a teletherapy
      machine in Goiania, Brazil. Subsequently, it was ruptured in a residential garden
      causing the dissemination of 137Cs throughout the city. Soil resuspension
      processes and burial of contaminated house waste in unused gardens were the major
      contributors to the Cs dissemination in soils at the secondary contaminated
      sites. Only locations within a radius of 50 m from the primary contaminated sites
      presented the need for remedial action. The radiation dose-rate measurements and
      the soil profiles were good indicators of the extent of the secondary
      contamination and were fundamental for the decisions taken regarding
      decontamination procedures. In cases of surface contamination, 60% on average of
      the total activity remained in the upper 1.5-cm layer over the first 5 mo after
      the accident, and topsoil removal proved to be an effective procedure for
      decontamination.

PMID- 1983992
TI  - Cesium-137 in the Goiania waterways during and after the radiological accident.
AB  - The main contamination areas in Goiania were exposed soil surfaces, and with the
      first rainfalls, 137Cs quickly reached the Meia-Ponte River, the main local
      waterway. Regular measurements of bottom sediment, surface water, and fish were
      begun 3 wk after the accident. In the first survey, 137Cs was detectable in
      sediments up to 12 km downstream from the accident area. Maximum 137Cs
      concentrations found in sediments of the Meia-Ponte River were 1.3 kBq kg-1 dry
      weight and 200 Bq kg-1 fresh weight for fish. Cesium-137 was always less than 10
      Bq L-1 in surface waters plus suspended particulates, even in the most
      contaminated creeks. Because it was the beginning of the rainy season, downstream
      sediment transport was enhanced. This resulted in a decrease of 137Cs
      concentrations in sediments of the urban area by a factor of approximately 20, 5
      wk after the accident. The main sedimentation area for suspended sediments in
      this portion of the river is the Rochedo Reservoir, which is 80 km downstream
      from the accident area. In a survey performed 10 mo after the accident, 137Cs
      concentrations in the reservoir were up to 14 Bq kg-1 for fish, 1 Bq kg-1 for
      aquatic plants, and 100 Bq kg-1 dry weight for bottom sediments.

PMID- 1983993
TI  - Model of kinetic behavior of deoxyglucose in heterogeneous tissues in brain: a
      reinterpretation of the significance of parameters fitted to homogeneous tissue
      models.
AB  - Effects of tissue heterogeneity on regional CMRglc (rCMRglc) calculated by use of
      the deoxyglucose (DG) method at 45 min following the pulse of DG were evaluated
      in simulation studies. A theoretical model was developed to describe the kinetics
      of DG uptake and metabolism in heterogeneous brain tissues. Rate constants were
      fitted to simulation data for mixed tissue and rCMRglc computed on the basis of
      this tissue heterogeneity model. The results were compared with those obtained by
      use of the original model of the DG method for homogeneous tissue, both without
      (3K model) and with (4K model) a term to describe an apparent loss of
      deoxyglucose-6-phosphate (DG-6-P). As a direct consequence of tissue
      heterogeneity, the effective rate constant for phosphorylation of DG, k3*,
      declined with time. To compensate for the time-changing k3*, estimates of the
      dephosphorylation rate constant, k4*, were artifactually high when the 4K model
      was used, even though no dephosphorylation of DG-6-P actually occurred. The
      present study demonstrates that the finding of a significant k4*, at least within
      45 min following a pulse of DG, may not represent dephosphorylation at all, but
      rather the consequence of measuring radioactivity in a heterogeneous tissue and
      applying a model designed for a homogeneous tissue. Furthermore, the high
      estimates of k4* resulted in significant overestimation of rCMRglc. When rCMRglc
      was computed with the conventional single-scan or autoradiographic method at 45
      min after a pulse of DG, the 3K and tissue heterogeneity models yielded values
      that were within 5% of the true weighted average value for the heterogeneous
      tissue as a whole. We conclude that the effects of tissue heterogeneity alone can
      give the appearance of product loss, even when none occurs, and that the use of
      the 4K model with the assumption of product loss in the 45-min experimental
      period recommended for the DG method may lead to overestimation of the rates of
      glucose utilization.

PMID- 1983994
TI  - Postischemic neuronal damage causes astroglial activation and increase in local
      cerebral glucose utilization of rat hippocampus.
AB  - The purpose of the present study was to determine the consequences of
      postischemic neuronal damage on CMRglc. Forebrain ischemia of 10 min duration was
      induced in male Wistar rats. The extent of neuronal damage and the numbers of
      immunocytochemically detected astrocytes in the hippocampal CA1 subfield as well
      as CMRglc were determined 2, 5, 7, and 14 days after ischemia. CBF was
      additionally measured 7 days postischemia. CMRglc was decreased in cortical and
      thalamic structures up to 5 days postischemia, and was normalized again on day 7
      after ischemia. In the hippocampal areas, CMRglc was decreased only on day 2
      after ischemia, was normalized after 5 days, and increased in the stratum oriens
      and pyramidale of the CA1 subfield from postischemic day 7 onward. Neuronal
      damage was clearly demonstrable 5 days after ischemia and further increased up to
      day 7. The number of GFAP-reactive astrocytes increased markedly at day 7
      postischemia. It is assumed that the activation of astrocytes is induced by
      neuronal damage, and that the astroglial metabolism is responsible for the
      increase in CMRglc of the CA1 subfield 7 days after ischemia. The decrease in CBF
      of the CA1 subfield 7 days after ischemia could be caused by a reduced density of
      perfused capillaries.

PMID- 1983995
TI  - Marked protection by moderate hypothermia after experimental traumatic brain
      injury.
AB  - These experiments examined the effects of moderate hypothermia on mortality and
      neurological deficits observed after experimental traumatic brain injury (TBI) in
      the rat. Brain temperature was measured continuously in all experiments by
      intraparenchymal probes. Brain cooling was induced by partial immersion (skin
      protected by a plastic barrier) in a water bath (0 degrees C) under general
      anesthesia (1.5% halothane/70% nitrous oxide/30% oxygen). In experiment I, we
      examined the effects of moderate hypothermia induced prior to injury on mortality
      following fluid percussion TBI. Rats were cooled to 36 degrees C (n = 16), 33
      degrees C (n = 17), or 30 degrees C (n = 11) prior to injury and maintained at
      their target temperature for 1 h after injury. There was a significant (p less
      than 0.04) reduction in mortality by a brain temperature of 30 degrees C. The
      mortality rate at 36 degrees C was 37.5%, at 33 degrees C was 41%, and at 30
      degrees C was 9.1%. In experiment II, we examined the effects of moderate
      hypothermia or hyperthermia initiated after TBI on long-term behavioral deficits.
      Rats were cooled to 36 degrees C (n = 10), 33 degrees C (n = 10), or 30 degrees C
      (n = 10) or warmed to 38 degrees C (n = 10) or 40 degrees C (n = 12) starting at
      5 min after injury and maintained at their target temperatures for 1 h.
      Hypothermia-treated rats had significantly less beam-walking, beam-balance, and
      body weight loss deficits compared to normothermic (38 degrees C) rats. The
      greatest protection was observed in the 30 degrees C hypothermia group.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1983996
TI  - Changes in pyruvate dehydrogenase complex activity during and following severe
      insulin-induced hypoglycemia.
AB  - The effect of severe insulin-induced hypoglycemia on the activity of the pyruvate
      dehydrogenase enzyme complex (PDHC) was investigated in homogenates of frozen rat
      cerebral cortex during burst suppression EEG, after 10, 30, and 60 min of
      isoelectric EEG, and after 30 and 180 min and 24 h of recovery following 30 min
      of hypoglycemic coma. Changes in PDHC activity were correlated to levels of
      labile organic phosphates and glycolytic metabolites. In cortex from control
      animals, the rate of [1-14C]pyruvate decarboxylation was 7.1 +/- 1.3 U/mg of
      protein, or 35% of the total PDHC activity. The activity was unchanged during
      burst suppression EEG whereas the active fraction increased to 81-87% during
      hypoglycemic coma. Thirty minutes after glucose-induced recovery, the PDHC
      activity had decreased by 33% compared to control levels, and remained
      significantly depressed after 3 h of recovery. This decrease in activity was not
      due to a decrease in the total PDHC activity. At 24 h of recovery, PDHC activity
      had returned to control levels. We conclude that the activation of PDHC during
      hypoglycemic coma is probably the result of an increased PDH phosphatase activity
      following depolarization and calcium influx, and allosteric inhibition of PDH
      kinase due to increased ADP/ATP ratio. The depression of PDHC activity following
      hypoglycemic coma is probably due to an increased phosphorylation of the enzyme,
      as a consequence of an imbalance between PDH phosphatase and kinase activities.
      Since some reduction of the ATP/ADP ratio persisted and since the
      lactate/pyruvate ratio had normalized by 3 h of recovery, the depression of PDHC
      most likely reflects a decrease in PDH phosphatase activity, probably due to a
      decrease in intramitochondrial Ca2+.

PMID- 1983997
TI  - GABAergic innervation in cerebral blood vessels: an immunohistochemical
      demonstration of L-glutamic acid decarboxylase and GABA transaminase.
AB  - The presence of GABAergic innervation in cerebral arteries of several species was
      investigated by an immunohistochemical method using antibodies against glutamic
      acid decarboxylase (GAD) and GABA transaminase (GABA-T). Both GAD and GABA-T
      immunoreactivities were found to be associated with large bundles and single
      fibers in the adventitial layer of arteries examined. The density and
      distribution pattern of both GAD- and GABA-T-immunoreactive fibers were found to
      be comparable at most regions examined. Both fibers were found to be most dense
      in the anterior cerebral artery and its adjacent part of the circle of Willis.
      Several peripheral arteries were found to receive very sparse or no GAD- and GABA
      T-immunoreactive fibers. Superior cervical ganglionectomy did not appreciably
      affect the distribution of both fibers. Cold-storage denervation, however,
      resulted in a drastic decrease in both fibers. At ultrastructural levels, both
      GAD- and GABA-T-immunoreactive nerve profiles were found to be very close to the
      smooth muscle cells. These results demonstrate the presence of a potentially
      functional GABAergic innervation in cerebral circulation. On few occasions, GAD
      immunoreactivities were also found in some endothelial cells, suggesting that a
      nonneuronal GABA system may also be present in cerebral arteries.

PMID- 1983998
TI  - Possible role of protein kinase C-dependent smooth muscle contraction in the
      pathogenesis of chronic cerebral vasospasm.
AB  - In the present study, we investigate the possible role of protein kinase C (PKC)
      dependent smooth muscle contraction in cerebral vasospasm following subarachnoid
      hemorrhage (SAH), employing the beagle "two-hemorrhage" model. The occurrence of
      chronic vasospasm was angiographically confirmed on day 7 in the basilar artery,
      which was exposed via the transclival approach. The artery was superfused with
      aerated Krebs-Henseleit solution containing various agents, and the subsequent
      changes in the basilar artery diameter were recorded by successive angiography.
      The preexisting spasm was not ameliorated by local application of
      neurotransmitter antagonists (atropine, methysergide, phentolamine, and
      diphenhydramine), calmodulin inhibitors (R24571 and W-7), or a calcium
      antagonist, nicardipine. However, the application of PKC inhibitors such as H-7
      and staurosporine induced significant dilation of the artery. In another
      experiment, an intrinsic PKC activator, 1,2-diacylglycerol (DAG), in the basilar
      artery, the CSF, and the cisternal clot of beagles exposed to two hemorrhages was
      measured on days 1, 2, 4, 7, and 14 using the DAG kinase method. On days 2, 4,
      and 7, the DAG content of the basilar artery showed a significant and prolonged
      increase (150-190% of control), whereas it was unchanged on days 1 and 14.
      Throughout the experimental period, there was a significant linear correlation
      between the DAG content and the angiographical diameter of the basilar artery.
      The above results indicate that SAH leads to an increase in the DAG level within
      the cerebral artery through an as yet unknown mechanism and that subsequent
      activation of the PKC-dependent contractile system participates in the occurrence
      of chronic vasospasm.

PMID- 1983999
TI  - Regional cerebral blood flow during spreading cortical depression in conscious
      rats.
AB  - Spreading cortical depression (SCD) of EEG activity was induced in one cerebral
      hemisphere of conscious restrained rats by direct current stimulation of the
      lateral frontal cortex. Regional CBF was measured using [14C]iodoantipyrine and
      brain dissection. An early phase of increased CBF was not measured in conscious
      rats, but an early relative hyperperfusion was measured if the resting CBF was
      first reduced by treatment with pentobarbital or indomethacin. A long-lasting
      reduction in CBF was measured in conscious rats following the passage of SCD.
      This flow reduction resolved after 3 h. In conscious rats, CBF decreased in the
      striatum and thalamus ipsilateral to the SCD, paralleling the CBF changes
      occurring in the cortex. The CBF change in these deep structures was abolished by
      pentobarbital. An early transient increase in regional CBF was measured in the
      cerebral cortex contralateral to the hemisphere involved with SCD in conscious
      rats. This early contralateral hyperperfusion was also abolished by pentobarbital
      or indomethacin but not by atropine or propranolol. The vascular response to SCD
      in conscious rats differs from that which occurs in anesthetized rats.

PMID- 1984000
TI  - Contractile and endothelium-dependent dilatory responses of cerebral arteries at
      various extracellular magnesium concentrations.
AB  - To clarify the effect of extracellular magnesium (Mg2+) on the vascular
      reactivity of feline isolated middle cerebral arteries, the effects of slight
      alterations in the Mg2+ concentration on the contractile and endothelium
      dependent dilatory responses were investigated in vitro. The contractions,
      induced by 10(-8)-10(-5) M norepinephrine, were significantly potentiated at low
      Mg2+ (0.8 mM v. the normal, 1.2 mM). High (1.6 and 2.0 mM) Mg2+ exhibited an
      inhibitory effect on the contractile responses. No significant changes, however,
      in the EC50 values for norepinephrine were found. The endothelium-dependent
      relaxations induced by 10(-8)-10(-5) M acetylcholine were inhibited by high (1.6
      and 2.0 mM) Mg2+. Lowering of the Mg2+ concentration to 0.8 mM or total
      withdrawal of this ion from the medium failed to alter the dilatory potency of
      acetylcholine. The changes in the dilatory responses also shifted the EC50 values
      for acetylcholine to the right. The present results show that the contractile
      responses of the cerebral arteries are extremely susceptible to the changes of
      Mg2+ concentrations. In response to contractile and endothelium-dependent
      dilatory agonists, Mg2+ probably affects both the calcium influx into the
      endothelial and smooth muscle cells as well as the binding of acetylcholine to
      its endothelial receptor. Since Mg2+ deficiency might facilitate the contractile
      but not the endothelium-dependent relaxant responses, the present study supports
      a role for Mg2+ deficiency in the development of the cerebral vasospasm.

PMID- 1984001
TI  - Measuring brain infarct volume.

PMID- 1984002
TI  - Direct measurement of the lambda of the lumped constant of the deoxyglucose
      method in rat brain: determination of lambda and lumped constant from tissue
      glucose concentration or equilibrium brain/plasma distribution ratio for
      methylglucose.
AB  - Steady-state distribution spaces of 2-[14C]deoxyglucose ([14C]DG), glucose, and 3
      O-[14C]methylglucose at various concentrations of glucose in brain and plasma
      ranging from hypoglycemic to hyperglycemic levels have been determined by direct
      chemical analyses in the brains of conscious rats. The hexose concentrations were
      measured chemically in freeze-blown brain extracted with ethanol to avoid the
      degradation of acid-labile products of [14C]DG back to free [14C]DG that has been
      found to occur with the more commonly used perchloric acid extraction of brain.
      Corrections were also made for nonphosphorylatable, labeled products of [14C]DG
      found in the nonacidic fractions of the brain extracts, which were previously
      included with the assayed [14C]DG, and for the contribution of the hexose
      contents in the blood in the brain, which was found to be particularly critical
      for the determination of the glucose distribution space, especially in
      hypoglycemic states. From the measured contents of the hexoses in brain and
      plasma, the relationships of the tissue concentrations and distribution spaces of
      each of the hexoses and of the lambda (i.e., ratio of tissue distribution space
      of DG to that of glucose) of the DG method to the tissue glucose concentration
      were derived. The lambda was then quantitatively related to the measured
      equilibrium ratio for [14C]methylglucose over the full range of brain and plasma
      glucose levels. By combining these new data with the values for the lumped
      constant, the factor that converts the rate of DG phosphorylation to glucose
      phosphorylation, previously determined in rats over the same range of plasma
      glucose levels, the phosphorylation coefficient was calculated and the lumped
      constant graphed as a function of the measured distribution space in brain for
      [14C]methylglucose.

PMID- 1984003
TI  - Metabolic maturation of the brain: a study of local cerebral glucose utilization
      in the developing cat.
AB  - Previously, using positron emission tomography (PET), we showed that local
      cerebral metabolic rates for glucose (lCMRglc) in children undergo dynamic
      maturational trends before reaching adult values. In order to develop an animal
      model that can be used to explore the biological significance of the different
      segments of the lCMRglc maturational curve, we measured lCMRglc in kittens at
      various stages of postnatal development and in adult cats using quantitative
      [14C]2-deoxyglucose autoradiography. In the kitten, very low lCMRglc levels (0.14
      to 0.53 mumol min-1 g-1) were seen during the first 15 days of life, with
      phylogenetically older brain regions being generally more metabolically mature
      than newer structures. After 15 days of age, many brain regions (particularly
      telencephalic structures) underwent sharp increases of lCMRglc to reach, or
      exceed, adult rates by 60 days. This developmental period (15 to 60 days)
      corresponds to the time of rapid synaptic proliferation known to occur in the
      cat. At 90 and 120 days, a slight decline in lCMRglc was observed, but this was
      followed by a second, larger peak occurring at about 180 days, when sexual
      maturation occurs in the cat. Only after 180 days did lCMRglc decrease to reach
      final adult values (0.21 to 2.04 mumol min-1 g-1). In general, there was good
      correlation between the metabolic maturation of various neuroanatomical regions
      and the emergence of behaviors mediated by the specific region. At least in the
      kitten visual cortex, which has been extensively studied with respect to
      developmental plasticity, the "critical period" corresponded to that portion of
      the lCMRglc maturational curve surrounding the 60-day metabolic peak. These
      normal maturational lCMRglc data will serve as baseline values with which to
      compare anatomical and metabolic plasticity changes induced by age-related
      lesions in the cat.

PMID- 1984004
TI  - Cerebrocerebellar relationship during behavioral activation: a PET study.
AB  - The effect of behavioral activation on cerebral and cerebellar glucose metabolism
      was studied in normal subjects when performing either a verbal memory task or a
      tactile somatosensory task. Each subject was also studied in a resting state
      control condition, either 1 h earlier or later than the activation task. Compared
      to the resting state, both tasks produced asymmetrical metabolic activation,
      which was opposite in direction within the cerebral and cerebellar hemispheres.
      In both tasks, the difference of activation of CMRglc in the right and left
      hemispheres in the cerebellum was negatively correlated with that in the sensory
      motor region. This apparently coupled metabolic activation of one cerebellum and
      areas within the opposite cerebral hemisphere represents the inverse of the
      crossed cerebellar diaschisis phenomenon commonly observed when a vascular lesion
      affects one cerebral hemisphere and hypometabolism occurs in the opposite
      cerebellum. Because these correlations were selective and concordant with known
      anatomical connections, and were found in two different tasks, they suggest
      strong functional connections between these specific brain regions.

PMID- 1984005
TI  - Simultaneous measurement of cerebral blood flow and energy metabolites in piglets
      using deuterium and phosphorus nuclear magnetic resonance.
AB  - This report demonstrates the feasibility of using deuterium (2H) and phosphorus
      (31P) nuclear magnetic resonance (NMR) spectroscopy to make multiple simultaneous
      determinations of changes in cerebral blood flow, brain intracellular pH, and
      phosphorylated metabolites for individual animals. In vivo spectra were obtained
      from the brains of newborn piglets immediately following an intracarotid bolus
      injection of deuterium oxide. Experiments were performed at magnetic field
      strengths of 1.9 T (2H NMR only) or 4.7 T (interleaved 2H and 31P NMR). The rate
      of clearance of deuterium signal was used to calculate cerebral perfusion rates
      (CBFdeuterium) during a stable control physiologic state and conditions known to
      alter blood flow. CBFdeuterium values measured at 1.9 T under conditions of
      control (normocarbia, normotension), hypercarbia, hypocarbia, and varying degrees
      of ischemia induced by hypotension showed a significant positive correlation with
      values measured simultaneously using radiolabeled microspheres (CBFdeuterium =
      0.4 x CBFmicrospheres + 8; r = 0.8). Simultaneous interleaved 2H and 31P NMR
      measurements under control conditions indicate that brain energy metabolites and
      intracellular pH remained at constant levels during the time course of the
      administration and clearance of deuterium oxide. Also, brain phosphorylated
      metabolites and intracellular pH did not differ significantly from their
      preinjection levels. Under control physiologic conditions, CBFdeuterium varied by
      +/- 6% and phosphorylated metabolite levels did not show a significant change
      with time, as measured from 15 blood flow determinations collected over 4 h. The
      results indicate that CBFdeuterium determinations have excellent reproducibility
      and do not affect brain energy metabolite levels. The procedures described here
      have the potential to bring a novel methodology to bear on investigating the
      relationship between cerebral perfusion and energy status during conditions such
      as ischemia or asphyxia.

PMID- 1984006
TI  - Effects of lesioning of the substantia innominata on autoregulation of local
      cerebral blood flow in rats.
AB  - Recently, accumulated data have suggested that the nucleus basalis
      magnocellularis, i.e., the substantia innominata (SI), may represent the primary
      source of central cholinergic innervation in the rat cortical vasculature. We
      therefore examined the effects of unilateral lesion of the SI on the
      autoregulation of local CBF (lCBF) during induced hypotension in rats. Male
      Wistar rats were divided into three groups. The animals of groups 1 and 2
      received an injection of 5 micrograms of ibotenate into the right SI
      stereotaxically. At 7 days after the injection, the lCBF was measured by the
      [14C]iodoantipyrine technique in the awake state. Group 1 was used as the
      normotensive group (MABP = 113.1 +/- 12.2 mm Hg). Group 2 formed the hypotensive
      group, and the lCBF was measured during hypotension (MABP = 80.0 +/- 5.5 mm Hg)
      induced by hemorrhage. Group 3, the sham-operated normotensive group, received
      vehicle injection into the right SI at 7 days prior to the lCBF measurement. In
      group 1, lCBF was significantly lower in the frontal, parietal, temporal, and
      striate cortices on the lesioned side compared to that on the contralateral side.
      In group 2, lCBF was significantly decreased in the cortices on the lesioned
      side, but there was no significant difference in magnitude of the lCBF reduction
      between groups 1 and 2. Group 3 exhibited no hemispheric asymmetries in lCBF.
      These findings suggest that the SI exerts an influence on cortical lCBF, but does
      not play a role in the autoregulation of lCBF during hypotension.

PMID- 1984007
TI  - Effects of topical adenosine analogs and forskolin on rat pial arterioles in
      vivo.
AB  - We utilized the closed window technique to study the in vivo responses of rat
      pial arterioles to superfused adenosine agonists. Adenosine and its analogs
      dilated pial arterioles and exhibited the following order of potency: 5'N
      ethylcarboxamide adenosine (NECA) greater than 2-chloroadenosine (2-CADO) greater
      than adenosine = R-N6-phenylisopropyladenosine (R-PIA) = S-PIA greater than N6
      cyclohexyladenosine (CHA). This potency profile suggests that cerebral
      vasodilation is mediated through the A2 receptor. Forskolin (10(-9) M)
      potentiated the vasodilation caused by 10(-6) M NECA, thus implicating adenylate
      cyclase activation during NECA-induced vasodilation and providing further support
      for involvement of the A2 receptor.

PMID- 1984008
TI  - Cortical microcirculation in a new model of focal laser-induced secondary brain
      damage.
AB  - To study the causes of spatial and temporal evolution of progressive neuro-injury
      in focal brain ischemia, models with consistent lesion topography are required.
      In such models, continuous monitoring of the microcirculation in a penumbral area
      undergoing progressive damage could be possible. We used a fixed-pulse (1.0 s, 40
      W) Nd-YAG laser (NYL) to produced discrete brain lesions in rats and monitored
      the cerebral blood flow (CBF) with laser-Doppler flowmetry (LDF) in nonirradiated
      areas directly adjacent to the maturing lesion. We also examined the time
      evolution of the lesion topography over a 4 day period. The lesion volume
      determined by histopathological methods increased from 3.1 +/- 0.5 to 4.5 +/- 0.5
      mm3 (p less than 0.05) during the first 2 h. Simultaneously, LDF indicated severe
      hypoperfusion (-60 +/- 21%, p less than 0.01) at a zone (1 mm distance from the
      laser lesion) where progressive neuronal degeneration and increased tissue water
      content (80.0 +/- 3.3% versus 76.8 +/- 2.1% in normal tissue, n = 7, p less than
      0.05) were also observed. At a 4 mm distance from the lesion, hyperemic CBF
      responses were observed, but no histopathological signs or edema. Secondary brain
      damage progressed up to 4 days (lesion volume of 6.0 +/- 0.7 mm3). The NYL
      induced brain lesion produced a highly reproducible focal injury and progressive
      neuronal death in a spatial relationship with microcirculatory failure and edema
      formation. The model allows prospective study of tissue state at a discrete zone,
      which is separate from the initial injury, but susceptible to secondary brain
      damage.

PMID- 1984010
TI  - The human-animal bond: implications for professional nursing.

PMID- 1984009
TI  - The effect of combined hypoxemia and cephalic hypotension on fetal cerebral blood
      flow and metabolism.
AB  - The effect of hypoxemia and cephalic hypotension, alone and in combination, on
      hemispherical CBF and metabolism was examined in seven chronically catheterized
      fetal sheep. Hypoxemia was induced by lowering the maternal inspired oxygen
      fraction and cephalic hypotension was generated by partial occlusion of the fetal
      brachiocephalic artery. CBF was measured with radionuclide-labeled microspheres.
      During control, the arterial blood oxygen content (CaO2) was 3.2 +/- 1.0 (SD) mM
      and CBF averaged 131 +/- 21 (SD) ml min-1 100 g-1. The cephalic perfusion
      pressure (PP, mean cephalic arterial-sagittal venous) was 40 +/- 4 mm Hg and
      cerebral vascular resistance (CVR, PP/CBF) was 0.31 +/- 0.06 mm Hg ml-1 min 100
      g. During induced hypoxemia, CaO2 was 1.4 +/- 0.7 mM and CBF was elevated to 223
      +/- 60 ml min-1 100 g-1. PP was not different from control and CVR was lower at
      0.19 +/- 0.04 mm Hg ml-1 min 100 g, reflecting cerebral vasodilation. With
      cephalic hypotension alone (PP = 21 +/- 4 mm Hg; CaO2 = 3.4 +/- 0.9 mM), CBF fell
      to 83 +/- 23 ml min-1 100 g-1 and there was no significant change in CVR (0.26 +/
      0.05 mm Hg ml-1 min 100 g). During combined hypoxemia and hypotension (CaO2 =
      1.5 +/- 0.8 mM and PP = 18 +/- 4 mm Hg), CBF was significantly greater than
      during hypotension alone (100 +/- 6 ml min-1 100 g). CVR was 0.19 +/- 0.05 mm Hg
      ml-1 min 100 g, identical to that measured in normotensive hypoxemia and
      significantly less than found during hypotension alone.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1984011
TI  - The significance of companion animals to a geriatric vascular patient: a case
      study.

PMID- 1984012
TI  - Health benefits of companion animals in relation to the physiologic indices of
      relaxation.

PMID- 1984013
TI  - The role of companion animals for persons with AIDS/HIV.

PMID- 1984014
TI  - Alzheimer's patients and their caregivers: the role of the human-animal bond.

PMID- 1984016
TI  - Health promotion: the influence of pets on life patterns in the home.

PMID- 1984015
TI  - "Here come the puppies": the power of the human-animal bond.

PMID- 1984017
TI  - Pet ownership and stress over the family life cycle.

PMID- 1984018
TI  - Pets and the family.

PMID- 1984019
TI  - The therapeutic functions of companion animals in infertility.

PMID- 1984020
TI  - Directions for the human-animal bond in the nursing education curriculum.

PMID- 1984022
TI  - Pet loss and the elderly.

PMID- 1984021
TI  - Nursing students and the elderly: enhancing intergenerational communication
      through human-animal interaction.

PMID- 1984023
TI  - Methods of measuring patient outcomes.

PMID- 1984024
TI  - Issues in outcomes research.

PMID- 1984025
TI  - History, development, and importance to nursing of outcomes research.

PMID- 1984026
TI  - The Agenda for Change: update on indicator development and possible implications
      for the nursing profession.

PMID- 1984027
TI  - Quality nursing care: the consumers' perspective revisited.

PMID- 1984028
TI  - Human response patterns to outcomes in the critically ill patient.

PMID- 1984029
TI  - Pain management as a quality of care outcome.

PMID- 1984030
TI  - Comprehensive assessment of caring and its relationship to outcome measures.

PMID- 1984031
TI  - Impact of spouse concordance of psychological adjustment on functional status
      after coronary bypass surgery.

PMID- 1984032
TI  - The policy and politics of patient outcomes.

PMID- 1984033
TI  - A shared governance model.

PMID- 1984034
TI  - Including nursing students in an agency quality assurance program.

PMID- 1984035
TI  - Different responsiveness of spleen lymphocytes from two lines of
      psychogenetically selected rats (Roman high and low avoidance).
AB  - Roman high- (RHA) and low-avoidance (RLA) rats have been genetically selected on
      the basis of their active avoidance behavior, and have been shown to differ on
      numerous behavioral, neurochemical and neuroendocrine parameters, especially in
      response to stress. We investigated the activity of splenic lymphocytes in vitro.
      Natural killer cell activity against YAC-1 tumoral cells and the mitotic response
      to plant lectins concanavalin A and phytohemagglutinin were much lower for
      lymphocytes isolated from RHA rats, in males as well as in females. The
      difference between the two strains was even larger when measured in a stressed
      state, immediately after active avoidance learning. On the other hand, the
      mitotic response to bacterial lipopolysaccharide, a B-cell-specific mitogen, was
      not different between the two lines, indicating that the difference in lymphocyte
      reactivity is limited to the T-lineage. The lower activity of T-cells in the RHA
      line had no consequence upon the ability of these animals to build up an antibody
      response against sheep red blood cells. These results indicate that Roman lines
      are an interesting animal model for the study of the relationships between the
      brain and the immune system, as well as for the analysis of the genes involved in
      the control of behavior.

PMID- 1984036
TI  - No association with HLA-DR, -DQ or -DP alleles in Guillain-Barre syndrome.
AB  - The distribution of HLA class II alleles in Guillain-Barre syndrome (GBS) has
      previously been reported only for HLA-DR. We report here the results of genomic
      typing for HLA-DR, -DQ and -DP allelic variability by restriction fragment length
      polymorphism analysis in 49 patients with a history of GBS. No association was
      found to HLA-DR, -DQ or -DP alleles or HLA-DR-DQ haplotypes. Subgrouping of
      patients according to severity of disease, as measured by disability or muscular
      weakness, or response to plasmapheresis treatment, also failed to reveal
      significant associations. These data suggest that HLA class II genes do not
      confer susceptibility to GBS.

PMID- 1984037
TI  - Suppression of actively induced and passively transferred experimental allergic
      neuritis by cyclosporin A.

PMID- 1984038
TI  - The effects of hydrostatic pressure on matrix synthesis in articular cartilage.
AB  - The direct effects of hydrostatic pressure on matrix synthesis in articular
      cartilage can be studied independently of the other factors that change during
      loading. We have found that the influence of hydrostatic pressure on
      incorporation rates of 35SO4 and [3H]proline into adult bovine articular
      cartilage slices in vitro depends on the pressure level and on the time at
      pressure. Pressures in the "physiological" range (5-15 MPa) applied for 20 s or
      for 5 min could stimulate tracer incorporation (30-130%) during the following 2
      h, but higher pressures (20-50 MPa) had no effect on incorporation rates. The
      degree of stimulation in cartilage obtained from different animals was found to
      vary; in some animals none was seen. Stimulation also varied with position along
      the joint. Physiological pressures (5-10 MPa) applied continuously for the 2-h
      incubation period also stimulated incorporation rates, but pressures greater than
      20 MPa always produced a decrease that was related to the applied pressure and
      that was reversible. These results suggests that the hydrostatic pressure that
      occurs during loading is a signal that can stimulate matrix synthesis rates in
      articular cartilage.

PMID- 1984039
TI  - Variables affecting disc size in the lumbar spine of rabbits: anesthesia,
      paralysis, and disc injury.
AB  - Methods have been developed that permit repetitive radiographic measurement of
      the lumbar intervertebral disc space in a rostral-caudal direction (width) in the
      anesthetized laboratory rabbit. Using isolated control discs and injured discs in
      which narrowing has been induced for chronic and acute periods, the widths of the
      lumbar intervertebral disc spaces determined ratio-graphically correlate with
      widths determined histologically (p less than 0.000, r = 0.75). Both an increase
      (widening) and a decrease (narrowing) in disc width were observed using
      radiography after different experimental treatments. Anesthesia and lower-body
      paralysis (an experimentally induced inability to bear weight on and to perceive
      a pinch stimulus in hind limbs) caused widening of the discs: anesthesia causing
      a general widening throughout the lumbar spine and lower-body paralysis causing a
      specific widening low in the lumbar spine. Both disc injection and piercing the
      disc with needles to recover nucleus pulposus material caused narrowing of the
      discs. Acridine-orange injection induced a narrowing accompanied by
      osteophytosis. Experimentally induced narrowing at L4-5 (the result of injury to
      the disc) resulted in narrowing also at L2-3. These findings are consistent with
      the hypothesis that in vivo disc-width size in the young rabbit depends on both
      the quantity of nucleus pulposus material and the force-generating activities of
      the adjacent spinal muscles, and that disc injury at one level stimulates
      narrowing at other levels.

PMID- 1984040
TI  - Demineralized allogeneic bone matrix for cartilage repair.
AB  - We tested the chondrogenic potential of demineralized allogeneic bone matrix
      (DABM) in the repair of osteochondral defects. In 42 adult rabbits, a 5-mm2 or 15
      mm2 defect was created bilaterally in the intercondylar groove of distal femur.
      DABM was inserted directly in 37 defects, whereas in 35 it was inserted after
      previous placement in muscle for 4, 16, or 19 days. Another 12 defects were left
      empty, serving as controls. Subgroups of animals were killed at 6, 12, 18, and 26
      weeks. The distal femora were excised and prepared for histologic evaluation in
      hematoxylin-eosin and toluidine blue. Cartilage-like repair tissue was observed
      in the majority of defects. However, there was a great variability in the
      experimental groups without any clear relationship to type of DABM implant,
      defect size, or postoperative time. Even individual knees exhibited varying
      stages of cartilage differentiation. Overall, DABM placed in muscle for 19 days
      appeared to yield the best repair of the defects. The most consistent findings of
      the present study were bone formation in the marrow of distal femur and, notably,
      the absence of bone differentiation toward the joint surface. Hence, it seems
      that the synovial environment prevents bone formation otherwise induced by DABM
      in vascular tissue. Although tissue formed in articular defects supplemented with
      DABM is of cartilaginous differentiation, which is retained over time, it is of
      highly variable quality. Hence, the described approach has to be optimized before
      it can be applied for the purpose suggested.

PMID- 1984041
TI  - Interaction between active and passive knee stabilizers during level walking.
AB  - The gait of normal subjects and patients with varus deformities at the knee was
      studied by analyzing the interaction between the dynamic (muscular) and passive
      (ligamentous) restraints affecting lateral stability of the knee. A statistically
      determinant model predicted that the midstance-phase adducting moment during
      normal gait would cause lateral knee joint opening if either antagonistic muscle
      force and/or pretension in the lateral soft tissues were not present at the knee.
      The patient group tended to compensate for a high midstance-phase adducting
      moment by walking with a style of gait that demanded more muscle force (greater
      flexion-extension moments). This walking style reduced the chance of lateral
      joint opening. It can be speculated that this style of gait would help to
      maintain equilibrium at the knee. The higher muscle force would aid in resisting
      the adducting moment, keeping the joint closed laterally and thus increasing the
      stability of the knee.

PMID- 1984042
TI  - The significance of skeletal magnetic resonance imaging after open bone biopsy.
AB  - The performance of a bone biopsy results in a dramatically altered magnetic
      resonance image (MRI) signal in both the biopsied segment and the surrounding
      bone. An experimental canine model was used to determine the cause and imaging
      sensitivity of this postbiopsy signal change in the adjacent intraosseous
      contents. Six dogs were used in the study. Half of the dogs had the cortical
      window left open, and the other half had a polymethylmethacrylate plug inserted.
      After hemostatic closure, images were obtained immediately postbiopsy and 6 weeks
      thereafter. MRI defect length was examined on both T1 and T2 weighted sequences
      at both time periods. After the final image was taken at 6 weeks, the bone was
      harvested and examined grossly and histologically for the purpose of making
      pathoradiographic correlations. The results suggest that magnetic resonance
      imaging is a sensitive method that accurately reflects the defect caused by bone
      biopsy and the surrounding hemorrhage. The defect length increased in size over
      time. The image was slightly smaller than the corresponding histologic response.
      Insertion of a cortical plug had no predictable effect on defect length, which
      depended upon the amount of pressurization used during insertion. We conclude
      that MRI may be useful in the staging of intraosseous primary neoplasms of bone
      after bone biopsy, especially in the detection of an iatrogenically induced
      tumor/hemorrhage margin. This may be critical when planning an intraosseous
      surgical resection in which short, wide margins are anticipated.

PMID- 1984043
TI  - Role of interfragmentary strain in fracture healing: ovine model of a healing
      osteotomy.
AB  - It has been hypothesized that the histological pattern of fracture healing is
      controlled at least in part by the local mechanical strains in the
      interfragmentary region. To test this "interfragmentary strain hypothesis," we
      applied cyclic bending deformations to tibial osteotomies in 11 sheep. An
      instrumented flexible plate spanning a 1-mm osteotomy gap was deformed to create
      a gradient of tissue elongation from 10% under the plate to 100% at the opposite
      cortex. The cyclic deformations were applied three times per minute, 24 h per
      day, for 1-5 weeks. However, as a result of tissue differentiation, the bone
      plate complex increased in stiffness with healing time, resulting in a marked
      reduction of the gap deformation at approximately 4 weeks. Fracture healing was
      evaluated using vascular injection of India ink and conventional histology. A
      nonlinear three-dimensional finite element model of the interfragmentary tissue
      at the initial stage of healing was used to predict the complex tissue strains.
      The ingrowth of vascularized soft tissue into the interfragmentary gap, as well
      as the subsequent differentiation of this tissue, occurred earlier and to a
      greater degree in regions of lower strain. In contrast, the proliferation of
      callus tissue was greatest at the periosteal and endosteal surfaces of the cortex
      opposite the plate. Direct comparison of the finite element predictions with the
      histology demonstrated that the spatial distribution of bone resorption at the
      fracture fragment ends directly corresponded to the locations of elevated tissue
      strain and stress. However, there was no consistent numerical relationship
      between the magnitude of these local peak strains and the corresponding volume of
      cortical bone resorption over the bone cross section.

PMID- 1984044
TI  - Three-dimensional kinematics of glenohumeral elevation.
AB  - To help resolve longstanding uncertainties about kinematics of the shoulder, we
      studied three-dimensional glenohumeral joint motion during arm elevation. A
      magnetic tracking system was used to monitor the three-dimensional orientation of
      the humerus with respect to the scapula. Appropriate coordinate transformations
      were then performed for the calculation of glenohumeral joint rotation based on
      the defined Eulerian angle. The effects of the plane of elevation and the humeral
      rotation on the magnitude of arm elevation were documented. The maximum humeral
      elevation at the glenohumeral joint took place in a plane anterior to the
      scapular plane. Maximum elevation in all planes anterior to the scapular plane
      required external axial rotation of the humerus. Conversely, internal axial
      rotation was necessary for maximum elevation posterior to the scapular plane.
      Quantifying the obligatory axial rotation explains the relationship of internal
      and external rotation with maximum elevation.

PMID- 1984045
TI  - The impact response of the seated subject.
AB  - An impact method for establishing the dynamic response of the seated subject is
      introduced. The method employs a pendulum to apply the impact to the suspended
      seat. Pins are placed in the spinous process at L3. Highly reproducible results
      are obtained. The results were not affected by the amplitude of impact, implying
      a linear system. A marked peak of transmissibility is found in the 4-5 Hz range
      and an attenuation peak is found close to 8 Hz. Both muscle contraction and
      postural changes affect the dynamic response. A relaxed posture shows greater
      gain and attenuation peaks. A valsalva stiffens the system and reduces the
      effective damping. The vertical response of the body probably shows in the 5-6 Hz
      peak, while the rotational response is probably encompassed in the 8 Hz
      attenuation peak.

PMID- 1984046
TI  - Monkey bone matrix induces bone formation in the athymic rat, but not in adult
      monkeys.
AB  - Demineralized bone matrix from young and adult monkeys was implanted
      intramuscularly for 6 weeks in athymic rats and adult monkeys. Cartilage and bone
      induction was evaluated by histology and calcium content. In the athymic rat,
      most implants induced cartilage or bone. In the monkeys, cartilage was formed
      only on rare occasions and there was no sign of bone formation. We conclude that
      (a) adult monkey bone matrix contains bone inductive properties; (b) these
      properties are not sufficient to induce bone formation in adult monkey muscle
      sites.

PMID- 1984047
TI  - Immunohistochemical and biochemical demonstration of calcium-dependent cysteine
      proteinase (calpain) in calcifying cartilage of rats.
AB  - Calpain is a Ca2(+)-dependent cysteine proteinase that has neutral pH optima.
      There are two classes of calpains that differ in their optimal calcium ion
      concentration for enzymatic activity. Calpain I requires a low concentration of
      Ca2+ for activation, and calpain II requires a much higher Ca2+ concentration.
      This report describes the immunohistochemical and biochemical demonstration of
      calpain II in calcifying cartilage in rats and also the degradation of the
      cartilage proteoglycan subunit by calpain II. Immunoperoxidase (peroxidase
      antiperoxidase) staining of the frozen sections of the knee joint from 3-day-old
      and 6-day-old Wistar rats, using polyclonal antibodies against the respective
      heavy subunits of calpains I and II, showed positive staining only with the anti
      calpain II antibody in the hypertrophic chondrocytes and surrounding
      cartilaginous matrix of the growth cartilage. Diethylaminoethyl-cellulose
      chromatography of the cartilaginous extract from 3-day-old rats showed a peak of
      caseinolytic activity attributable to calpain as well as an inhibitory peak of
      calpastatin, a specific inhibitor protein of calpains. Immunoblotting using the
      anti-calpain II antibody of the calpain peak demonstrated identity with the heavy
      subunit of calpain II (80 kDa). Proteoglycan-degrading activity of calpain was
      assessed using porcine kidney calpain II and the porcine articular cartilage
      proteoglycan subunit. After incubation in the presence of Ca2+, degradation of
      proteoglycan was demonstrated by the change of the elution position on Sepharose
      2B chromatography. It is possible that calpain functions as one of the
      proteoglycan-degrading proteolytic enzymes of growth cartilage. Intracellular
      localization of calpain in hypertrophic chondrocytes also suggests a role in the
      hypertrophic process of the chondrocyte in growth cartilage.

PMID- 1984048
TI  - The effects of initial end contact on medial collateral ligament healing: a
      morphological and biomechanical study in a rabbit model.
AB  - In this investigation, the effect of initial end contact on medial collateral
      ligament (MCL) healing was studied in the rabbit model. Sixty-eight 1-year-old
      New Zealand white rabbits were separated into two groups. In one group, a 4 mm
      saggital Z-plasty was performed in the right MCL midsubstance (contact group),
      and in the other group, an analogous 4 mm midsubstance segment was removed (gap
      group). Left knees were unoperated to serve as internal contralateral MCL
      controls. Animals had unrestricted cage activity until sacrifice in groups of
      eight at 3, 6, 14, and 40 weeks postoperatively. Early results demonstrated that
      contact and gap injuries healed with what appeared to be scar tissue both
      morphologically and biomechanically. In both groups, laxities recovered to their
      contralateral values within 6 weeks and biomechanical viscoelastic behaviors
      recovered to 68-92% of contralaterals by 14-40 weeks. Despite these similarities,
      contacts showed morphological and biomechanical evidence of improved healing over
      gaps. Contact scars remodeled more quickly, recovered laxity more quickly, and
      were generally closer to contralaterals than gaps in terms of their structural
      strength, stiffness, and material behaviors, after 40 weeks of healing. With the
      exception of appearances and failure stress, all measured properties of contact
      healing MCLs were statistically indistinguishable from contralateral MCLs at 40
      weeks of healing. These advantages of contact healing in this model support
      speculations that there are differences in the early rate and possibly in the
      later quality of ligament healing when cut rabbit MCL ends are in proximity.
      Longer-term studies to define end points and mechanisms of healing are required.

PMID- 1984049
TI  - Biomechanical evaluation of a biodegradable composite as an adjunct to internal
      fixation of proximal femur fractures.
AB  - Internal fixation of comminuted unstable fractures of the severely osteoporotic
      proximal femur is sometimes supplemented with polymethyl-methacrylate (PMMA). We
      here report an in vitro biomechanical evaluation of a biodegradable particulate
      composite that might be used for similar purposes. The composite includes a
      matrix phase consisting of a hydrolyzable prepolymer [polypropylene fumarate
      (PPF)] cross-linked with methacrylate monomer, and a particulate phase consisting
      of tricalcium phosphate and calcium carbonate. We implanted dynamic hip screws in
      22 cadaveric proximal femora and measured the yield load for an oblique force
      applied to the femoral head. The hip screws were then reinforced with either PMMA
      or the PPF composite and tested again. On the basis of analysis of variance, the
      average increases in yield load for PMMA and PPF reinforcement of 1,750 and 1,130
      N were statistically significant (p less than 0.00005), suggesting that both
      materials enhance congruence between implant and bone and thereby increase the
      projected load-bearing area of the implant. The increase in yield force with PMMA
      was slightly higher than the increase with PPF (p less than 0.05), but both
      values after reinforcement were close (3,790 +/- 561 N for PMMA vs. 3,240 +/- 669
      N for PPF). If we can demonstrate that appropriate rates of degradation, bony
      ingrowth, and static and fatigue properties can be achieved in vivo with this
      system, our data suggest that this PPF composite may have potential as an adjunct
      to the internal fixation of unstable fractures of the osteoporotic hip.

PMID- 1984050
TI  - Rerouting peripheral nerves for spinal cord lesions.
AB  - To provide control of paralyzed limb muscles following spinal cord lesions,
      peripheral nerves containing motor axons from motoneurons located above a spinal
      cord lesion could potentially be rerouted to nerves containing motor axons
      located below the spinal cord lesion. To test this hypothesis in rats, the distal
      end of a cut tibial nerve, innervated by the L4-6 spinal level, was anastomosed
      or rerouted to the central end of the cut femoral nerve, innervated by the L3-4
      spinal level. Appropriate controls were used. Recovery of lower hind limb motor
      function was followed at regular intervals, measuring the twitch tension of toe
      flexion (innervated by the tibial nerve) induced by transcutaneous stimulation of
      nerve rootlets exiting the spinal cord. After 4-6 months, 54% of motor function
      returned in the experimental group. Retrograde transport of horseradish
      peroxidase from the gastrocnemius muscles to spinal motoneuron cell bodies
      confirmed that the innervation of this group was at a higher level. Furthermore,
      after an L4 spinal transection, twitch tension responses to spinal cord outlet
      stimulation remained only in the experimental group. Therefore, a peripheral
      nerve containing motor axons from above the lesion was rerouted to a distal
      peripheral nerve to control muscles that would have otherwise been denervated.

PMID- 1984051
TI  - The influence of scoliosis and ageing on proteoglycan heterogeneity in the human
      intervertebral disc.
AB  - Proteoglycans (PGs) purified from 19-year-old male (19M), 53-year-old female
      (53F), and 15-16-year-old adolescent idiopathic scoliotic (AIS) disc tissues were
      characterised by their aggregation properties with hyaluronic acid (HA),
      glycosaminoglycan (GAG), and amino acid composition, electrophoretic mobilities
      by composite agarose polyacrylamide gel electrophoresis (CAPGE), and hydrodynamic
      size by Sepharose CL2B gel permeation chromatography. Proteoglycan levels were
      similar in the AIS and 53F discs, but considerably higher levels were found in
      the 19M discs. Proteoglycan populations assessed by the aforementioned criteria
      demonstrated a similar level of heterogeneity in the AIS and 53F discs but this
      differed with the 19M sample. Two small Mr, low buoyant density PG species were
      particularly prominent in AIS and 53F discs: these were similar to two
      nonaggregating PG species formerly reported by di Fabio et al.; however, the
      corresponding PG species in 19M discs were of somewhat different composition.
      Collectively, these data suggest similar processing of PGs in the AIS and 53F
      discs. Furthermore, the pattern of normal age changes in the PGs from AIS discs
      appears to be disturbed, most likely arising as a consequence of the abnormal
      biomechanical forces intrinsic to the deformity.

PMID- 1984052
TI  - Histochemical and ultrastructural observations on brown degeneration of human
      intervertebral disc.
AB  - Thirty-eight fresh human intervertebral discs collected during anterior interbody
      fusion surgery were histochemically and ultrastructurally analyzed for pigments.
      Macroscopically, five stages of degeneration were classified according to the
      color, fibrosis, and fragility of the nucleus pulposus of the discs. In order to
      demonstrate lipofuscin granules, specimens were subjected to special staining
      procedures, including carbol fuchsin lipofuscin stain, the Schmorl's reaction,
      and autofluorescence. Lipofuscin granules were distributed from the inner layer
      of the annulus fibrosus to the nucleus pulposus. Such granules were numerous in
      cases of slight or severe degeneration, whereas fewer granules were found in
      cases of moderate degeneration. However, the stage of macroscopic degeneration of
      the intervertebral disc did not necessarily correlate with the incidence of
      lipofuscin granules. By ultrastructural observation, the morphological features
      of the components of the intervertebral disc and the ultrastructure of the
      lipofuscin granule were clarified. The ultrastructure of the "brown degeneration"
      disc exhibited markedly increased amorphous electron-dense bodies located among
      collagen fibrils in the matrix.

PMID- 1984053
TI  - Orthostatic hypotension in human immunodeficiency virus infection may be the
      result of generalized autonomic nervous system dysfunction.
AB  - We used an autonomic nervous system (ANS) testing battery to determine if
      generalized ANS dysfunction was present in five human immunodeficiency virus
      positive (HIV+) patients presenting with severe orthostatic hypotension (OH). All
      five patients had abnormal ANS testing, which demonstrated both sympathetic and
      parasympathetic defects, i.e., generalized ANS dysfunction. Treatment with
      fludrocortisone effectively reversed the OH in four of the five patients. The OH
      was transient in these four patients. We believe it is important to recognize
      that OH may be the result of generalized ANS dysfunction in HIV-positive patients
      and that it can be effectively treated.

PMID- 1984054
TI  - Identification of membrane anchorage domains of the HIV-1 gp160 envelope
      glycoprotein precursor.
AB  - The gp41 transmembrane protein of human immunodeficiency virus type 1 (HIV-1)
      contains a hydrophobic membrane-spanning domain that serves to anchor the gp120
      gp41 complex on the surface of infected cells and virions. To study the
      requirements for membrane anchorage, conservative amino acid substitutions in
      three residues at a time were made within this hydrophobic gp41 region. The
      complete gp160 precursor as well as the gp120 exterior envelope glycoprotein were
      exported into the supernatant of expressing cells for two mutants with amino acid
      substitutions in residues 687-689 and 697-699. The soluble gp160 molecules
      exhibited a binding ability for CD4 on the surface of SupT1 cells that was 33-36%
      that of the soluble gp120 glycoproteins. These results implicate residues 687-689
      and 697-699 as important components of the stop-transfer signal that anchors the
      gp160 envelope glycoprotein precursor in the membrane. The data also suggest that
      characteristics in addition to hydrophobicity are required for stop-transfer
      signals.

PMID- 1984056
TI  - Transmission of human immunodeficiency virus from monocytes to epithelia.
AB  - Physical contact between latent HIV-infected monocytes and epithelial cells
      appears to trigger rapid assembly and release of HIV into the enclosed space
      between donor and acceptor cells. During this process, monocytes form microvilli
      that intimately associate with epithelial membrane. HIVs sequestered in these
      sites are then internalized in the epithelial cells within phagocytic endosomes.
      Morphological evidence suggests that parts of virions fuse with the endosomal
      membrane and escape into the cytoplasm of the epithelium before endosome-lysosome
      fusion. In addition, virions in the lysosomal compartment are not necessarily
      degraded and may cause dissolution of phagolysosome membrane before HIV is
      damaged. This is reflected in the observation of free coated virions in the
      epithelial cytoplasm. Apart from the phagocytic mode of HIV entry, two other less
      common routes of HIV penetration were observed. One resembles direct HIV fusion
      with host membrane, which is similar to the entry mode of virus into CD4
      lymphocytes. The second mode of entry resembles receptor-mediated endocytosis
      characterized by small pits and endosomes. Cell contact-mediated viral shedding
      and the diversity of HIV entry mechanisms are described for an in vitro model.

PMID- 1984055
TI  - Castanospermine vs. its 6-O-butanoyl analog: a comparison of toxicity and
      antiviral activity in vitro and in vivo.
AB  - Inhibitors of glycoprotein processing, such as castanospermine (1,6,7,8
      tetrahydroxyoctahydroindolizine), have been shown previously to inhibit human
      immunodeficiency virus type 1 (HIV-1) with acceptable toxicity in cultured human
      cells. In prior experiments, we have tested the toxicity and antiviral efficacy
      of castanospermine in mice infected with the Rauscher murine leukemia virus
      (RLV). When compared with 3'-azido-3'-deoxythymidine (AZT, zidovudine),
      castanospermine was less effective and more toxic. Since the 6-O-butanoyl analog
      of castanospermine was previously found to have a more favorable activity profile
      than the parent compound against HIV-1 in cultured cells, we compared the
      antiviral efficacy of both compounds in parallel in vitro and in vivo in the RLV
      system. Plaque formation in the XC assay was inhibited with a 50% inhibitory
      concentration (IC50) of 2.4 microM for the 6-O-butanoyl analog of
      castanospermine, as compared to 9 microM for castanospermine. For both compounds,
      concentrations resulting in significant cytotoxicity were about ten times higher.
      Both compounds significantly decreased HIV-1 env-induced syncytium formation in a
      novel in vitro assay. In RLV-exposed mice, the 6-O-butanoyl analog showed no
      advantage over the parent compound: both curves for toxicity as well as antiviral
      efficacy were super-imposable. We conclude that the 6-O-butanoyl analog of
      castanospermine as well as castanospermine itself are active antiviral agents in
      mice and that prolonged oral administration is tolerable. However, in comparison
      to AZT, their antiviral activity profiles are less favorable.

PMID- 1984057
TI  - Pharmacokinetics of zidovudine (azidothymidine). III. Effect of pregnancy.
AB  - Administration of zidovudine (ZDV or azidothymidine) to pregnant women with HIV
      infection may be of benefit to both the mother and her unborn child. Since
      pregnancy can have a substantial effect on the pharmacokinetics of a drug, the
      effect of pregnancy on the pharmacokinetics of ZDV (10 mg/kg, i.v. bolus) was
      studied in the macaque (Macaca nemestrina). The plasma clearance, steady-state
      volume of distribution, and terminal half-life of ZDV were found not to be
      significantly affected by pregnancy. Based on these findings, we predict that the
      pharmacokinetics of ZDV in women will not be affected by pregnancy. If this
      prediction is found to be correct, the dose of ZDV need not be adjusted when the
      drug is administered to pregnant women.

PMID- 1984058
TI  - Is the incubation period of AIDS lengthening?
AB  - Data from a cohort study of 1,637 homosexual men in Los Angeles are used to
      estimate the distribution of times from HIV infection to AIDS, and to detect any
      changes in the distribution. We find weak, but not statistically significant,
      evidence that the incubation period is lengthening. When the incubation period
      distribution is assumed not to have changed, we estimate that the proportion
      developing AIDS within 6 years of HIV infection is 27%, with a 95% confidence
      interval of (23%, 31%). However, if we assume that the incubation period
      distribution began to change in July 1987, then we estimate that for individuals
      infected in the first half of 1979, 28% develop AIDS within 6 years, and for
      those infected in the first half of 1983, 25% develop AIDS in 6 years. Four
      different hypotheses are suggested for a lengthening of the incubation period;
      these are a treatment hypothesis, a cofactor hypothesis, a better health care
      hypothesis, and a changing virus and disease hypothesis. The statistical method
      used is semiparametric modeling of the joint distribution of the date of
      infection and the incubation period for the participants in the study. These
      methods, although computationally intensive, are an attractive way of analyzing
      data from a prevalent cohort because only minimal parametric assumptions are
      made.

PMID- 1984059
TI  - Epidemiology of acquired immune deficiency syndrome in persons aged 50 years or
      older.
AB  - Acquired immune deficiency syndrome (AIDS) has afflicted persons of all ages, yet
      only recently has attention been devoted to AIDS in older persons. To examine the
      epidemiology of AIDS in persons greater than or equal to 50 years old in the
      United States, we analyzed cases reported to the Centers for Disease Control. The
      number reported annually in persons greater than or equal to 50 years old
      increased from 13 in 1981 to 3,562 in 1989. Through December 1989, 11,984 had
      been reported, representing 10% of all cases. Although male homosexual contact
      accounted for most cases in persons aged 50-69, blood transfusion became a more
      common means of exposure with increasing age, accounting for 28% of cases in
      persons aged 60-69 and 64% of cases in individuals aged greater than or equal to
      70. The proportion of women increased from 6.1% in persons with AIDS aged 50-59
      to 28.7% of those aged greater than or equal to 70. The proportion of AIDS
      diagnoses made in the same month as death increased from 16% in persons aged 50
      59 to 37% in those aged greater than or equal to 80, suggesting either more rapid
      progression of disease or increasing delay in diagnosis. As the incidence in
      older persons continues to increase, clinicians caring for older patients must
      become more familiar with AIDS.

PMID- 1984060
TI  - A unified hypothesis for three cardinal features of HIV immunology.

PMID- 1984061
TI  - Age preference in sexual choice and the spread of HIV into the general
      population.

PMID- 1984062
TI  - Priapism as a complication of sickle cell disease.

PMID- 1984063
TI  - The percutaneous operative gastrostomy for gastric decompression in major
      urological surgery.
AB  - When postoperative gastric decompression is necessary a percutaneous gastrostomy
      tube is an alternative to nasogastric intubation. The percutaneous insertion of a
      suprapubic bladder catheter is an easy procedure without notable complications
      that increases the comfort of the patient in the immediate postoperative period.
      We advocate its use in all major urological abdominal operations.

PMID- 1984064
TI  - Early assessment of penile curvatures in infants.
AB  - A noninvasive office procedure was developed for evaluation of penile curvatures
      in infants, in whom photography of this erectile deformity at home is difficult.
      By applying negative pressure with 2, 60 ml. syringes, penile engorgement and
      rigidity that mimic a natural erection could be achieved in 16 infants.

PMID- 1984065
TI  - Ureteral triplication and ureterocele: report of 3 cases and review of the
      literature.
AB  - We report 3 cases of ureterocele associated with ureteral triplication and review
      the literature. Ureteral triplication was type I in 2 patients and type II in 1.
      Diagnosis was established preoperatively in 2 cases and intraoperatively in 1.
      All patients were initially treated by upper pole partial nephrectomy and
      aspiration of the ureterocele, leaving the ureteral stump open in the
      retroperitoneum. Subsequent excision of the ureterocele and ureteral
      reimplantation for persistent ipsilateral vesicoureteral reflux and recurrent
      urinary tract infections were required in 2 cases.

PMID- 1984066
TI  - Ureteral triplication: double extravesical ureteral ectopia.
AB  - A 21-month-old girl presented with ureteral triplication, representing an
      exceptional variant of Smith's type 1. One ureter was intravesical and the other
      2 were extravesical (bladder neck and vaginal).

PMID- 1984067
TI  - Short-term and long-term changes in renal function after donor nephrectomy.
AB  - We retrospectively examined the effect of nephrectomy on renal function in 55
      living related donors. Renal function was measured with 131iodine
      orthoiodohippurate scans. All patients were studied preoperatively, and 1 week
      and 1 year postoperatively. In 20 patients 10-year followup was available.
      Compensatory hypertrophy was complete 1 week postoperatively: effective renal
      plasma flow of the remaining kidney was 32.5% higher than preoperatively. The
      increase remained stable for at least a year. The degree of compensatory
      hypertrophy was significantly greater in male patients (46.9% after 1 week) than
      in female patients (26.7%). Compensatory hypertrophy occurred in all age groups
      studied and it was most pronounced in patients less than 30 years old. In the
      patients followed for 10 years effective renal plasma flow decreased from 387.7
      ml. per minute 1 week after nephrectomy to 367.4 ml. per minute at 10 years. This
      result is similar to the decrease seen in the normal population. According to our
      results, renal donation by living related persons does not lead to long-term
      decrease in renal function.

PMID- 1984068
TI  - Treatment of idiopathic retroperitoneal fibrosis by immunosuppression.
AB  - Idiopathic retroperitoneal fibrosis is exceedingly uncommon in childhood and its
      etiology is uncertain. Support for an immunological basis for the disease is
      given by a report of a 14-year-old girl with severe retroperitoneal fibrosis
      causing progressive azotemia in whom azathioprine and prednisolone were used
      successfully. This case supports the efficacy of immunotherapy in the treatment
      of idiopathic retroperitoneal fibrosis.

PMID- 1984069
TI  - Ischiopagus tetrapus twins: urological aspects of separation and 10-year
      followup.
AB  - Conjoined twins occur once in 50,000 births. Only 6% of conjoined twins are of
      the ischiopagus type in which the twins are joined symmetrically at the pelvis
      and fusion begins at the level of the common umbilicus. The longitudinal axis
      extends in a straight line in opposite directions and the genitourinary and
      gastrointestinal tracts are shared. Tetrapus is a subtype in which all 4 lower
      extremities are present and oriented at right angles to the axis of the common
      trunk. Two sets of female ischiopagus tetrapus twins were born in 1977 and
      successfully separated at the St. Louis Children's Hospital in the following
      year. We describe the genitourinary and associated anomalies, surgical separation
      and long-term urological followup of these 2 sets of ischiopagus tetrapus twins.

PMID- 1984071
TI  - Substance abuse-related spontaneous bladder rupture: report of 2 cases and review
      of the literature.
AB  - Spontaneous rupture of the normal bladder associated with alcohol abuse is rare,
      with only 20 cases reported in the English literature to which we add 2 cases.
      Heavy alcohol ingestion predisposes the bladder to rupture by the large volume of
      fluid intake, its diuretic effect and the mental obtusion it produces, clouding
      sensory cues to void. alpha-Sympathomimetic drugs, such as cocaine and
      methamphetamine, increase the resistance at the urethral sphincter and exacerbate
      the effects of alcohol. Cystography will be diagnostic, and prompt operative
      repair of intraperitoneal rupture is mandatory. Complete evaluation of the
      bladder, including urodynamic study, is important to eliminate underlying bladder
      pathological conditions. Substance abuse-related rupture demonstrates a typical
      constellation of clinical features that necessitate considering it a syndrome
      separate from other causes of spontaneous bladder rupture.

PMID- 1984072
TI  - Bladder outlet obstruction due to pelvic lipoma: computerized tomography,
      magnetic resonance imaging and radiographic evaluation.
AB  - We report an unusual case of long-standing bladder outlet obstruction due to
      pelvic lipoma in a 31-year-old white man. The mass was evaluated by plain film,
      computerized tomography and magnetic resonance imaging. The differential
      diagnosis of fat-containing extraperitoneal pelvic masses is discussed.

PMID- 1984070
TI  - Highly sensitized patients with delayed graft function: a management protocol.
AB  - The postoperative management of the highly sensitized renal transplant recipient
      with delayed graft function on cyclosporine is complicated. Allografts with
      delayed graft function are reported to have a 20 to 30% poorer 1-year survival
      than allografts without delayed graft function. Several factors may be implicated
      in this poorer 1-year survival. A decrease in or cessation of cyclosporine dosage
      frequently is used in an attempt to minimize nephrotoxicity. Such under
      immunosuppression can result in irreversible rejection. Occasionally, a
      pessimistic view of the prognosis for the transplant may result in early
      abandonment of the allograft with discontinuation of immunosuppression and
      allograft nephrectomy. We report on 3 highly sensitized patients whose kidneys
      had delayed graft function and were deliberately maintained on high doses of
      cyclosporine throughout the period of delayed graft function. Each graft achieved
      function (2, 4 and 5 months) after transplantation. The serum creatinine levels
      20, 28 and 38 months after transplantation were 2.7, 2.0 and 1.0 mg./dl.,
      respectively. We suggest that the maintenance of high cyclosporine levels
      throughout the delayed graft function period is useful in highly sensitized
      recipients and was an important factor in their successful outcome. A management
      protocol for such patients is proposed.

PMID- 1984073
TI  - En bloc transplantation of kidneys from donors weighing less than 15 kg. into
      adult recipients.
AB  - En bloc transplantation of kidneys from donors who weighed less than 15 kg. into
      20 adult patients is described. Intraperitonealization of the medial kidney
      allowed adequate renal positioning and growth. Graft venous thrombosis occurred
      in 1 patient and irreversible graft rejection occurred in 4 patients. Graft
      survival was 65% with excellent function at a mean followup of 8.8 months. En
      bloc transplantation of pediatric cadaver kidney grafts in adults is an
      acceptable procedure.

PMID- 1984074
TI  - Adenocarcinoma of the urachus associated with elevated levels of CA 125.
AB  - Adenocarcinoma of the urachus is a rare genitourinary tumor with a poor
      prognosis. The treatment of choice is en bloc surgical resection, although
      combination therapy with surgery and chemotherapy has been used with mixed
      results. We describe a 69-year-old woman with adenocarcinoma of the urachus and
      elevated serum levels of CA 125 tumor marker. She was treated with resection plus
      5-fluorouracil, doxorubicin and mitomycin, alternating with platinum-based
      chemotherapy. The serum CA 125 level decreased precipitously after the operation
      and became normal after 2 months of chemotherapy. The patient remained free of
      disease 1 year postoperatively. Serum CA 125 may be a useful tumor marker for
      urachal carcinoma and adjuvant chemotherapy may be effective in treating the
      disease.

PMID- 1984075
TI  - Unresectable calcified bladder tumor: hemiacidrin irrigation as an adjunct to
      resection.
AB  - Radiographic calcification of urothelial malignancies is an uncommon finding. To
      our knowledge, calcification of transitional cell carcinoma of the bladder
      preventing transurethral resection has not been reported previously. We report a
      case of an initially unresectable radiopaque bladder tumor and discuss the
      successful, conservative management with continuous bladder irrigation with
      hemiacidrin followed by complete transurethral resection.

PMID- 1984076
TI  - Rectourethral fistula caused by Kaposi's sarcoma.
AB  - A 35-year-old man with the acquired immunodeficiency syndrome-related complex was
      evaluated for a persistent urethral discharge, pneumaturia and watery diarrhea.
      Radiographic and endoscopic procedures established the diagnosis of a
      rectourethral fistula. Perineal exploration and excision of the fistula revealed
      the pathological diagnosis of Kaposi's sarcoma. The differential diagnosis of an
      acquired rectourethral fistula and the significance of Kaposi's sarcoma are
      discussed.

PMID- 1984077
TI  - A lethal complication of papaverine-induced priapism.
AB  - A large series of patients was treated for impotence with intracorporeal
      injections of papaverine and phentolamine with no major complications and no
      deaths reported. We report on a 45-year-old black man with advanced multiple
      sclerosis who died after such therapy. When the first self-administered injection
      of phentolamine and papaverine failed to produce an adequate erection the patient
      injected a second dose that resulted in priapism and death of massive pulmonary
      embolism.

PMID- 1984078
TI  - Adenocarcinoma of the prostate in a 41-year-old man with XXY karyotype and
      chronic lymphocytic leukemia: report of a case.
AB  - We report a case of adenocarcinoma of the prostate in a 41-year-old man with
      47XXY karyotype (Klinefelter's syndrome) and chronic lymphocytic leukemia. The
      increased incidence of malignancy in individuals with Klinefelter's syndrome has
      been well documented for certain neoplasms. Adenocarcinoma of the prostate has
      not been reported previously in a patient with Klinefelter's syndrome and a 47XXY
      karyotype. Absence of mosaicism was confirmed by peripheral lymphocyte, skin
      fibroblast, bone marrow cell and spleen stroma fibroblast cultures. Chronic
      lymphocyte leukemia, especially the T-cell cytotoxic/suppressive variant, may
      additionally add to an immunological deficit. Since carcinoma of the prostate,
      Klinefelter's syndrome and chronic lymphocytic leukemia are common, the lack of a
      previous report is interesting. Etiological aspects are discussed.

PMID- 1984079
TI  - Exaggerated venous mural hypertrophy in association with metastatic
      adenocarcinoma of the prostate.
AB  - A 61-year-old black man presented with metastases to the right groin 5 years
      after 125iodine treatment for a well differentiated primary prostatic
      adenocarcinoma. Medium sized veins within and immediately adjacent to the
      neoplasm showed marked mural thickening due to hypertrophy and hyperplasia of the
      inner circular and outer longitudinal muscles. There was no histological evidence
      of radiation effect in the stroma or in the tumor cells. We could find no report
      in the literature of such changes associated with metastatic carcinoma.

PMID- 1984080
TI  - Re: Attempted nonoperative management of blunt renal lacerations extending
      through the corticomedullary junction: the short-term and long-term sequelae.

PMID- 1984081
TI  - Re: Inferior vena caval invasion by renal cell carcinoma: false positive
      diagnosis by venacavography.

PMID- 1984083
TI  - Presence of a low capacity androgen receptor in the gubernaculum of the pig
      fetus.
AB  - The aim of our study was to investigate the theory that the gubernaculum is an
      androgen-responsive structure responsible for fetal testicular descent. Using 3H
      methyltrienolone (3H-R1881) as ligand, we performed a seven-point Scatchard
      analysis of androgen receptor binding in the gubernaculum, prostate, urethra and
      striated muscle tissue obtained from pig fetuses between 60 and 109 days of
      gestation. The gubernaculum demonstrated androgen receptor binding with an
      affinity and capacity significantly lower than that of fetal pig prostate and
      urethra, but not significantly different from that of striated muscle taken from
      both male and female fetuses. A marked increase in the size and mass of the
      gubernaculum of male (but not female) fetuses is known to accompany testicular
      descent. If the dramatic increase in the mass of the gubernaculum observed in
      male (but not female) fetuses were the result of androgen stimulation, it may be
      expected that the striated muscle mass (and therefore total body mass) of male
      fetuses should be greater than that of female fetuses, since the androgen
      receptor affinity and capacity of the gubernaculum is similar to that of striated
      muscle. However, we found no significant difference in total body mass between
      male and female pig fetuses at the same period of gestation. These findings raise
      doubt concerning the theory that growth of the gubernaculum during descent is the
      result of androgen stimulation.

PMID- 1984082
TI  - End stage renal disease serum contains a specific renal cell growth factor.
AB  - End stage renal disease (ESRD) kidneys display abnormal growth characterized by a
      continuum of cystic disease, adenoma and carcinoma. This study evaluates the
      hypothesis that serum of patients with ESRD contains increased amounts of a
      growth factor which specifically induces proliferation of renal cells. ESRD sera
      compared to sera from normal controls induced a two to three-fold increase in the
      proliferative rate of renal cell carcinoma cell lines and normal kidney explants
      compared to cell lines from other sites. The increased proliferative activity of
      ESRD sera on renal cells was paralleled by an increase in cytosolic free calcium.
      The growth factor activity was encoded by a polypeptide of between 15 and 30 kd.
      The activity of ESRD sera on renal cells was not mimicked or inhibited by
      epidermal growth factor, basic fibroblast growth factor and platelet derived
      growth factor indicating that the renal cell specific growth factor activity in
      ESRD is different from these factors.

PMID- 1984084
TI  - Enhancing effect of partial cystectomy on rat urinary bladder carcinogenesis.
AB  - The effects of 5% and 50% partial cystectomies on bladder tumorigenesis initiated
      with N-butyl-N-(4-hydroxybutyl)nitrosamine(BBN) were investigated in Wistar rats
      by examining the histological findings and cell proliferative activity. The
      incorporation of bromodeoxyuridine (BrdUrd) into the DNA synthesis phase was
      determined by an in-vitro labeling technique. After eight weeks of treatment with
      drinking water containing 0.05% BBN, 5% or 50% partial cystectomy was performed
      at the end of week 16, and the resected bladder was sutured with dexon or silk.
      There was no difference in the incidence of papillary or nodular (PN) hyperplasia
      between the control and partial cystectomy groups. However, the incidence of
      cancer in the group given partial cystectomy was much higher than that in the
      control. All the cancers in the control group were grade-1 superficial tumors,
      whereas grade-2 or invasive tumor was observed in six of 40 animals in the
      partial cystectomy group. The 31.0% labeling index of cancer in the partial
      cystectomy group was greater than the 24.1% in the control group. There was also
      a significant difference in the number of BrdUrd-labeled cells in PN hyperplasia
      between the control and partial cystectomy groups. These findings indicate that
      partial cystectomy enhances BBN-initiated bladder carcinogenesis and the increase
      in DNA synthesis found in PN hyperplasia and cancer may be associated with the
      induction of bladder tumors.

PMID- 1984085
TI  - Paradoxical effects of cyclosporine on concanavalin A-induced blastogenesis.
AB  - The effects of increasing in vitro cyclosporine concentrations (0, 50 100 or 200
      ng./ml.) on lymphocyte blastogenesis, measured by incorporation of tritiated
      thymidine and induced by varying levels of concanavalin A (0, 0.25, 1.0 or 5.0
      ng./ml.), were studied in regard to mean serum level of cyclosporine in 26 renal
      allograft recipients. Results were compared to similar data obtained in healthy
      controls. Patients were divided into group 1 (13 patients, mean serum
      cyclosporine trough level less than 150 ng./ml.) and group 2 (13 patients,
      cyclosporine level greater than 150 ng./ml.). With no cyclosporine added to the
      assay proliferation of lymphocytes obtained from all patients inversely
      correlated to the mean serum trough cyclosporine level at all stimulatory levels
      of concanavalin A (0.25 ng./ml., p less than 0.01; 1.0 ng./ml., p less than 0.001
      and 5.0 ng./ml., p less than 0.001) and was significantly lower than in controls
      (p less than 0.0002). Whereas increasing in vitro cyclosporine concentrations has
      produced the expected increase in suppression of blastogenesis in controls and
      group 1, a paradoxical effect became evident in group 2. Under stronger
      stimulatory conditions (concanavalin A 1.0 or 5.0 ng./ml.) increasing in vitro
      cyclosporine concentrations were associated with significantly decreased
      suppression of blastogenesis (p less than 0.01) compared to group 1. These
      results confirm previous reports and suggest that the duality of effect of
      cyclosporine in this in vitro model may be related to its functional relationship
      to the calcium ion (Ca++)/calmodulin complex and to its cellular
      concentration/solubility curve. These considerations may be of importance in
      adjusting cyclosporine dosage based on serum trough levels of cyclosporine.

PMID- 1984086
TI  - Cytotoxic effects of high energy shock waves in different in vitro models:
      influence of the experimental set-up.
AB  - High energy shock waves (electromagnetically generated, Siemens Lithostar) were
      studied for their effects in vitro on different (tumor) cell types. Cells were
      exposed to the shock waves as a single cell suspension or as a cell pellet on the
      bottom of a test tube. In both cases, a dose dependent direct cytotoxicity,
      established by trypan blue dye exclusion, was observed after treatment with 1000
      or 2000 shock waves. Also, the antiproliferative capacity as determined by
      clonogenic potential (double layer soft agar) and growth rate (plastic) were
      affected in this way. However, comparing the results after treatment in
      suspension or pellet, a discrepancy was evident. The cell lines showed a
      different susceptibility in pellet vs. suspension. Also the differential
      sensitivity of the cell types varied in these two treatment models. Furthermore
      the outcome depended on the cell concentration; direct cytotoxicity in a cell
      suspension was more pronounced at higher cell concentrations, while in a pellet
      this was increased by decreasing the number of cells. Finally, no shock wave
      induced cytotoxicity could be seen after fixation of cells in gelatine or by
      placing the pellet on a bottom layer of gelatine. Pressure measurements revealed
      no adequate explanation for this phenomenon. These results indicate that in vitro
      effects depend on the way cells are exposed to the shock waves and can be greatly
      influenced by changing the conditions of the microenvironment. Therefore, precise
      descriptions of the experimental set-up and careful interpretations of their
      outcome are obligatory.

PMID- 1984087
TI  - Influence of indomethacin on the adherence of urease-induced crystals to rat
      bladder epithelium.
AB  - The mucous coat lining the urinary tract has a barrier function which prevents
      bacteria and crystals from adhering to the uroepithelium. The mucous coat of the
      gastric mucosa is sensitive to prostaglandins, and prostaglandin synthetase
      inhibitors induce gastric erosions and disrupt the continuity of the mucous
      lining. To determine whether prostaglandin synthetase inhibitors also exert a
      similar effect on the uroepithelium, rats were given indomethacin
      intraperitoneally or orally. The effect of this treatment on the adhesion of
      urease-induced crystals to rat bladder mucosa was studied using a previously
      developed in-vivo method. Both when given intraperitoneally and orally in a dose
      of one mg. per kg. b.w. for six weeks, indomethacin significantly increased
      crystal adherence. This constitutes indirect evidence for the concept that
      prostaglandins influence the mucous coat of the rat urinary tract and reduce its
      antiadhesive properties.

PMID- 1984088
TI  - The effect of chronic renal insufficiency on cyclosporine nephrotoxicity.
AB  - Despite cyclosporine's efficacy in preventing rejection, its use has been
      hampered by nephrotoxicity. Questions remain concerning its application in
      patients with decreased renal function. The purpose of this study was to 1)
      establish a reliable animal model with chronic renal insufficiency (CRI) to study
      cyclosporine (CyA) nephrotoxicity, and 2) compare the long-term (50 day) severity
      of CyA nephrotoxicity in CRI versus normal animals. Fischer 344 rats were divided
      into six groups (15 to 22 each). In three groups, CRI was induced by a 5/6th
      nephrectomy (three groups were sham operated). After three wks., daily i.p.
      injections of olive oil, CyA at five mg./kg., or CyA at 30 mg./kg. daily were
      administered. Serum and urine were collected at 10 day intervals for the
      determination of biochemical indices of renal function. Animals were sacrificed
      after 50 days of treatment and renal histology was evaluated by light and
      electron microscopy. Chronic CyA treatment was well tolerated by both intact and
      CRI rats, suggesting that this is a reliable model for long-term CyA toxicity
      studies. CyA decreased renal function at day 50 in both CRI and intact animals.
      CRI of mild to moderate degree had little effect on the biochemical and
      histological indices of CyA induced nephrotoxicity. CRI does appear to potentiate
      the metabolic toxicity that occurs after chronic treatment with high dose CyA.

PMID- 1984089
TI  - The impact of alcohol ingestion on erections in rats as measured by a novel bio
      assay.
AB  - In rats, a syndrome of yawning and penile erection results from the
      administration of low doses of apomorphine, a dopamine receptor agonist shown to
      stimulate dopamine autoreceptors. Ethanol has been shown to influence dopamine
      metabolism. Low doses of ethyl alcohol (0.25 mg./kg.) failed significantly to
      alter apomorphine-induced yawning or penile erection, while 0.5 mg./kg. decreased
      erectile behavior but did not significantly alter the number of yawns. A
      reduction in both yawning and penile erection in response to apomorphine
      challenge was seen after the acute intraperitoneal injection of relatively high
      doses (1.0-3.0 mg./kg.) of ethanol. Two possible mechanisms of action may explain
      these phenomena. Alcohol may interfere with dopaminergic receptor mechanisms, or
      conversely, alcohol, through its actions on central dopamine metabolism may alter
      a second neurotransmitter/neuropeptide more directly responsible for the
      production of apomorphine-induced yawning and penile erection, possibly oxytocin.

PMID- 1984090
TI  - Immunotherapy of murine bladder cancer by irradiated tumor vaccine.
AB  - This investigation explored the efficacy of irradiated autologous mouse bladder
      tumor (Ir-MBT2) as an active specific immunotherapeutic agent and as adjuvant
      therapy with Bacillus Calmette-Guerin (BCG) against a subcutaneously transplanted
      murine bladder tumor. Tumor incidence was significantly reduced in groups
      receiving BCG (27%, p less than 0.005) or Ir-MBT2 with BCG (53%, p less than
      0.025), compared to control (93%). Survival was significantly improved in groups
      treated with BCG (100%, p less than 0.005), 10(5) Ir-MBT2 with BCG (53%, p less
      than 0.01), or 10(7) Ir-MBT2 with BCG (47%, p less than 0.025) compared with
      control (13%). Surprisingly, Ir-MBT2 consistently reduced the efficacy of BCG
      alone. Ir-MBT2 alone (10(7)) appeared to enhance tumor growth. Autologous
      irradiated bladder tumor vaccine, alone or in combination with BCG, displayed no
      immunotherapeutic advantage. The use of irradiated tumor cell vaccine for bladder
      cancer therapy may reduce the results achievable with BCG alone.

PMID- 1984091
TI  - The effects of basic fibroblast growth factor and suramin on cell motility and
      growth of rat prostate cancer cells.
AB  - Suramin, a new type of cancer chemotherapeutic agent with growth factor
      antagonist properties, has been reported to affect growth of prostate cancer
      metastatic lesions. Partin et al. have previously reported that prostate cancer
      cell motility was essential for tumor cell metastasis. We have studied the
      effects of suramin on cell motility and cell growth in a prostate cancer cell
      model. We have demonstrated that suramin has differential effects on rat prostate
      cancer cells in vitro. The effects of suramin on cell growth were biphasic. At
      low concentrations of 0.01 mM and 0.1 mM, suramin stimulated growth while it was
      inhibitory at a higher concentration of 1.0 mM, and 10 mM suramin resulted in
      cell death. Cell motility was inhibited at a suramin concentration above 0.1 mM.
      The inhibition of cell motility by suramin may be through the blockage of growth
      factor effects. Reducing serum growth factor concentration reduced cell motility
      and the motility was restored by the addition of basic fibroblast growth factor
      (bFGF) to the media. Motility which had been restored by bFGF could then be
      blocked by the presence of suramin. The inhibition of cell motility by suramin is
      reversible on washout of the drug. Suramin inhibits cell motility in both the
      human prostate cancer cells (LNCaP) and the rat (MLL).

PMID- 1984092
TI  - Surgical management and prognosis of renal cell carcinoma invading the vena cava.
AB  - A total of 44 patients with renal cell carcinoma and vena caval tumor thrombus
      underwent surgical resection. Of these patients 27 had primary tumor confined
      within Gerota's fascia, negative lymph nodes and no distant metastases (stage
      T3cN0M0). Patients who underwent extraction of a mobile tumor thrombus from the
      vena cava had a 69% 5-year survival rate (median 9.9 years) but patients with
      tumor thrombus directly invading the vena cava had a 26% 5-year survival rate
      (median 1.2 years), which improved to 57% (median 5.3 years) if the involved vena
      caval side wall was resected successfully. Of these patients 17 had renal cell
      carcinoma with vena caval thrombus as well as extrafascial extension, regional
      lymphadenopathy or distant metastases, and the 5-year survival rate was less than
      18% in all groups (median survival less than 0.9 years). Prognosis was determined
      by the pathological stage of the renal cell carcinoma and by the presence or
      absence of vena caval side wall invasion but not by the level of tumor thrombus
      extension. Patients with incomplete resection of localized renal cell carcinoma
      with tumor thrombus do not survive any longer than those with extensive cancer,
      positive lymph nodes or distant metastases. However, when partial venacavectomy
      establishes negative surgical margins then survival markedly improves.

PMID- 1984093
TI  - Endourological experience with cystine calculi and a treatment algorithm.
AB  - Between May 1984 and January 1988, 18 patients (31 pyeloureteral units) with
      documented symptomatic cystine stones were treated. Stone size ranged from 5 to
      56 mm. in largest diameter, with an average of 21 mm. All pyeloureteral units
      were treated initially by endourological methods, including ureteroscopy in 10,
      percutaneous ultrasonic lithotripsy in 9, extracorporeal shock wave lithotripsy
      (ESWL) in 10 and chemolysis in 2. Of the patients 10 required a combination of
      these technologies and 2 required an open operation. Of the 31 units 23 were free
      of stones when the patient was discharged from the hospital. Of 8 patients with
      retained stones only 3 had fragments greater than 3 mm. in diameter. Based on
      this experience an algorithm was developed for the urological management of
      cystine stones. Ureteral calculi may be removed by ureteroscopic techniques or
      manipulated into the renal pelvis and managed as renal stones. Cystine renal
      calculi of less than 1.5 cm. may be treated with ESWL monotherapy. Stones of 1.5
      to 3 cm. may be treated with ESWL and dissolution, or percutaneous ultrasonic
      lithotripsy plus dissolution. Staghorn calculi may be treated by percutaneous
      ultrasonic lithotripsy plus ESWL and/or dissolution for retained fragments.

PMID- 1984094
TI  - Afferent nipple valve malfunction caused by anchoring collar: an unexpected late
      complication of the Kock continent ileal reservoir.
AB  - In the construction of a Kock continent ileal reservoir for urinary diversion,
      significantly high rates of late postoperative complications regarding nipple
      valves, the efferent limb in particular, have been reported. There are only a few
      reports on afferent nipple valve malfunction. A total of 42 patients who
      underwent a Kock pouch operation and were observed for more than 12 months (mean
      38 months) was evaluated in terms of afferent nipple valve malfunction. Late
      afferent nipple valve complications were observed in 10 of the 42 patients (24%).
      These complications included erosion of the polyester fiber fabric used as a
      collar (5 patients), stenosis of the afferent limb (2) and obstruction of the
      afferent nipple by a mucous plug or fungus ball (3). The latter 2 complications
      were due to mechanical or dynamic obstruction of urine flow caused by a
      nonabsorbable collar. None of the 10 patients had problems with efferent nipple
      valve function. Our results suggest that the peristaltic direction of the
      intestine and the use of nonabsorbable material as a collar are primarily
      responsible for the late afferent nipple valve complications. Further
      modifications are needed to produce a stable nipple valve. Otherwise, simpler and
      more reliable alternative techniques of antireflux anastomosis should be
      considered.

PMID- 1984095
TI  - Tamm-Horsfall autoantibodies in interstitial cystitis.
AB  - Interstitial cystitis presents a diagnostic and therapeutic challenge. Although
      many etiologies, including autoimmunity, have been proposed its pathogenesis
      remains obscure. Tamm-Horsfall protein has been identified in the superficial
      urothelium of patients with interstitial cystitis demonstrating abnormal
      urothelial permeability. Eight patients with a clinical diagnosis of interstitial
      cystitis underwent cystoscopy and bladder biopsy. Characteristic cystoscopic
      findings were present, and each patient had chronic inflammation and mast cells
      by histopathological analysis. Preoperative anti-Tamm-Horsfall protein serum
      antibody (IgG) titers were determined by enzyme-linked immunosorbent assay (range
      500 to 8,000, mean 2,750). A control group of 8 patients with a negative
      urological history also had titers of 0 to 500 (p = 0.02). The humoral response
      to Tamm-Horsfall protein in these patients suggests a role for Tamm-Horsfall
      protein in interstitial cystitis. Measurement of serum Tamm-Horsfall protein
      antibody may prove to be useful as a noninvasive diagnostic test in patients with
      this disease.

PMID- 1984096
TI  - Progression of stage T1 bladder tumors after intravesical bacillus Calmette
      Guerin.
AB  - Of 221 patients with superficial bladder tumors (stages Ta, Tis and T1) treated
      by transurethral resection and an initial 6-week course of intravesical bacillus
      Calmette-Guerin (BCG) 195 were evaluated after 3 months for local response. Of
      these patients 17 (8.7%) had a stage T1 tumor, of whom 14 (82%) subsequently had
      muscle invasion (7), uncontrolled local disease (6) or metastasis (1). The median
      interval to progression was 8.4 months, which was significantly (p = 0.0001) less
      than among the other 178 patients with a nonstage T1 lesion or no tumor found at
      3 months, of whom 44 (25%) had progression (median more than 5 years). These data
      suggest that patients with stage T1 tumor 3 months after BCG therapy require
      additional therapy other than simple tumor resection and meticulous followup.

PMID- 1984097
TI  - Results of contemporary radical cystectomy for invasive bladder cancer: a
      clinicopathological study with an emphasis on the inadequacy of the tumor, nodes
      and metastases classification.
AB  - We reviewed 261 patients who underwent a radical operation at a single
      institution as definitive treatment of invasive bladder cancer to evaluate the
      survival and accuracy of the tumor, nodes and metastasis system in characterizing
      the prognosis. Between January 1979 and June 1987 the 261 evaluable patients
      underwent 1-stage radical cystectomy with pelvic node dissection and urinary
      diversion. No chemotherapy and/or radiation therapy was given before or after the
      operation. The postoperative mortality rate was 1.8%. The over-all staging error
      between clinical and pathological stages was as high as 44%. The over-all
      actuarial 5-year survival rate was 54.5%. The 5-year survival rates were 75% for
      stage pT1, 63% for stage pT2, 31% for stage pT3 and 21% for stage pT4 disease. A
      significant difference in the survival (p less than 0.002) was observed in stage
      pT3 by dividing tumors confined within the bladder wall (pT3a, 50%) from those
      extending throughout the bladder wall (pT3b, 15%). A careful evaluation of
      transitional cell involvement of the prostate in stage pT4a cancer led to the
      identification of 2 different patterns: 1) contiguous when a bladder tumor
      extended directly into the prostate through the bladder wall and 2) noncontiguous
      when a bladder tumor and a transitional cell carcinoma of the prostate were found
      simultaneously. These patterns had completely different (p less than 0.05)
      survival rates (6 versus 37%). The patients with high grade tumors had a worse
      prognosis in comparison with those with grades 1 and 2 tumors (41 versus 56%, p
      less than 0.005). The over-all 5-year survival of patients with positive nodes
      was 4% in comparison with 60% of those without nodal involvement (p less than
      0.001). Despite current optimal surgical treatment, nearly 50% of all patients
      with invasive bladder cancer continue to die. The need for a modification of the
      current tumor, nodes and metastasis tumor classification to provide the clinician
      a more reliable staging system for planning treatment modalities is indeed
      mandatory.

PMID- 1984098
TI  - Total bladder replacement using detubularized sigmoid colon: technique and
      results.
AB  - We performed total bladder replacement with a detubularized segment of sigmoid
      colon in patients after cystoprostatectomy. The surgical technique and long-term
      results in 27 patients are reported. This neobladder configuration compared
      favorably with other neobladder types regarding ease of construction. The
      surgical complications were acceptable. Initial reservoir function was good but
      improved further with time. After 1 year the capacity averaged 600 cc, pressures
      during filling and at capacity were low (average 12 and 16 cm. water) and
      emptying was satisfactory (residual urine 4 to 80 cc). All patients were
      continent during the day and 67% were continent at night without excessive
      voiding habits. Nighttime incontinence was further resolved in 2 patients by
      using the AMS 800 artificial sphincter around the bulbous urethra. The
      detubularized sigmoid is an excellent neobladder configuration after
      cystoprostatectomy.

PMID- 1984099
TI  - Intracavernous injection of prostaglandin E1 in combination with papaverine:
      enhanced effectiveness in comparison with papaverine plus phentolamine and
      prostaglandin E1 alone.
AB  - We compared the erectile response to intracavernous injection of a combination of
      papaverine and prostaglandin E1 with that of a combination of papaverine and
      phentolamine (49 patients), and prostaglandin E1 alone (38). The degree of
      erection achieved was significantly better with papaverine plus prostaglandin E1
      than with papaverine plus phentolamine and the duration of erection was less,
      although the incidence of prolonged erections (greater than 5 hours) was similar
      with both combinations. Papaverine with prostaglandin E1 likewise resulted in a
      significantly better degree of erection than prostaglandin E1 alone (prolonged
      erections occurred only after the drug combination). All erections subsided
      spontaneously and none required medical intervention throughout the study. Pain
      was noted only after injection of prostaglandin E1. The incidence was clearly
      lower (7 of 38 versus 13 of 38) after the injection of only 5 micrograms.
      prostaglandin E1 in combination with papaverine (although the difference is not
      statistically significant). Subjectively, the side effects caused by the drug
      combination were described as much less dramatic by the patients than after
      prostaglandin E1 alone. The combination of papaverine and prostaglandin E1 shows
      a clearly synergistic effect and might suitably replace papaverine plus
      phentolamine or prostaglandin E1 alone in patients who do not respond well or
      suffer side effects after high single doses.

PMID- 1984100
TI  - The fate of residual fragments after extracorporeal shock wave lithotripsy
      monotherapy of infection stones.
AB  - We reviewed 53 patients with infection stones treated by extracorporeal shock
      wave lithotripsy (ESWL*) monotherapy to determine the long-term rate free of
      stones and the stone recurrence rate as correlated with the pre-treatment stone
      burden and the radiological presence of sand or fragments after the procedure.
      Long-term followup (mean 26.6 months) was available on 33 patients representing
      38 kidneys. Although only 3 kidneys were free of stones immediately after ESWL,
      20 were without stones at 3 months and 18 (47%) were stone-free at followup. Of 9
      kidneys with fragments of more than 5 mm. after the final treatment 7 (78%) had
      residual fragments at 3 months and experienced stone progression. Of 9 kidneys
      with sand remaining 6 (66%) and all 3 kidneys that appeared to be free of stones
      after ESWL were without stones at followup. The 3-month plain film of the
      kidneys, ureters and bladder was a reliable indicator of eventual outcome. Of 20
      kidneys that were free of stones at 3 months 16 remained without stones. Of 18
      kidneys with residual stone particles at 3 months 14 showed disease progression,
      2 had stable disease and 2 passed residual sand. Only 1 of 17 patients who were
      free of stones or had stable stone disease had a positive urine culture at
      followup. Patients with infection stone fragments 3 months after ESWL monotherapy
      have a high rate of stone progression (78%) and should undergo further treatment.
      ESWL monotherapy of infection stones requires close patient followup to assure
      that all residual fragments have passed and urine remains sterile.

PMID- 1984102
TI  - Priapism associated with the sickle cell hemoglobinopathies: prevalence, natural
      history and sequelae.
AB  - To determine the prevalence and characteristics of priapism associated with
      sickle cell hemoglobinopathic conditions we interviewed and examined 52 men with
      sickle cell anemia, 10 with sickle C disease, 3 with sickle B(+)-thalassemia and
      19 with sickle cell trait. Of the men 20 with sickle cell anemia (38%) and 1 with
      sickle B(+)-thalassemia (33%) reported past priapism attacks. Average patient age
      at onset in the sickle cell anemia patients was 19 years (range 8 to 30 years).
      Four men had had only 1 attack. The average number of attacks per year in the
      remaining patients ranged from 1 to 52. Of the patients who reported multiple
      attacks the average duration of a typical episode and the duration of the longest
      self-limiting episode was 1.6 and 7.0 hours, respectively. Six patients had
      experienced 1 attack that persisted for longer than 24 hours. There were no
      significant differences between the clinical and hematological parameters of the
      sickle cell anemia patients who did and did not experience priapism or of the
      priapism patients who had and had not experienced episodes lasting greater than
      24 hours. Six patients had been hospitalized for priapism and 4 were treated with
      a shunting procedure. Of the latter patients 2 were impotent but there was no
      significant alteration in the sexual function of the other study participants.

PMID- 1984101
TI  - Pathophysiology of prolonged penile erection associated with trazodone use.
AB  - Treatment with the antidepressant trazodone has been associated with the
      occurrence of prolonged penile erection and priapism. To evaluate the effect of
      trazodone on erection we monitored the periodic physiological sleep-related
      erections in 6 healthy volunteers in a double-blind crossover study comparing the
      effect of trazodone, trimipramine (a tricyclic antidepressant) and placebo. In
      addition, to determine the effects of trazodone on the neurovascular control of
      penile smooth muscle we performed in vitro studies on corpus cavernosum tissue
      obtained from patients undergoing penile prosthesis implantation. Trazodone
      significantly increased the total interval of nocturnal erectile activity, while
      trimipramine had no effect. During the high dose treatment (nights 4 and 5) the
      average duration of erectile activity per night with placebo was 158 +/- 41
      minutes (mean +/- standard deviation) for night 4 and 177 +/- 21 minutes for
      night 5. During trazodone treatment the erectile activity per night was
      significantly prolonged to 285 +/- 115 minutes during night 4 and 232 +/- 86
      during night 5 (p less than 0.01). Analysis of the erectile activity in relation
      to the rapid eye movement sleep period during which erectile activity usually
      occurs revealed that the detumescence phase of erection, under sympathetic
      control, was significantly prolonged an average of 2.4 times by trazodone
      compared to placebo (p less than 0.05). In vitro, trazodone at concentrations
      comparable to those reached in plasma significantly impaired corporeal smooth
      muscle contractions elicited by electrical stimulation of adrenergic nerves and
      antagonized contractions induced by exogenous norepinephrine. We conclude that
      trazodone can enhance penile erection in man and propose a mechanism related to
      the alpha-adrenoceptor blocking properties of trazodone by interference with the
      sympathetic control of penile detumescence.

PMID- 1984103
TI  - Penile implants in the treatment of Peyronie's disease.
AB  - The treatment of Peyronie's disease remains controversial. Patients who fail
      conservative therapy may require surgical intervention to restore the ability to
      have sexual intercourse. Plaque excision and dermal grafting have not been
      universally successful, and alternate procedures that rely on the placement of a
      penile prosthesis have gained in popularity. We reviewed our experience with 35
      patients with advanced Peyronie's disease treated with a penile prosthesis.
      Preoperatively, 55% of the patients were unable to engage in intercourse due to
      pain or angulation of the penis and 25% were unable to achieve any erection at
      all. Postoperatively, with a mean followup of 6.9 years, 88% of the patients were
      able to engage in intercourse and were satisfied with the results obtained. In
      selected patients with advanced disease the implantation of a penile prosthesis
      remains a highly successful and satisfying alternative for the treatment of
      Peyronie's disease.

PMID- 1984104
TI  - Biochemical analysis of electroejaculates in spinal cord injured men: comparison
      to normal ejaculates.
AB  - To address the consistent finding of asthenospermia in spinal cord injured men we
      compared the biochemical constituents of antegrade fractions of electroejaculates
      of 6 such patients with the manual ejaculates of 6 volunteers. Semen samples in
      each group were analyzed for 19 biochemical parameters, pH and osmolality.
      Organic components included triglycerides, glucose, fructose, uric acid,
      creatinine, urea, total protein, albumin and cholesterol. Metabolic enzymes,
      including glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase,
      lactate dehydrogenase and alkaline phosphatase, were measured. Inorganic
      constituents included chloride, sodium, potassium, zinc and phosphorous. Although
      not significant, higher levels of blood urea nitrogen and creatinine were
      demonstrated in most electroejaculates suggesting urinary contamination of the
      antegrade specimens. In electroejaculates significantly lower levels (p less than
      0.05) of fructose, albumin, GOT and alkaline phosphatase as well as significantly
      higher levels (p less than 0.05) of chloride were noted. No significant
      difference in osmolality or pH was found. Moreover, in the electroejaculates the
      levels of glucose, uric acid and all inorganic constituents approached their
      corresponding levels in serum. We conclude that biochemical abnormalities of the
      seminal plasma may contribute to seminal dysfunction of spinal cord injured men
      and may result from neurological injury to the accessory sex glands or from the
      electroejaculation procedure itself.

PMID- 1984105
TI  - Prevalence of carcinoma in situ and other histopathological abnormalities in
      testes from 399 men who died suddenly and unexpectedly.
AB  - To determine the prevalence of carcinoma in situ of the testis and other
      testicular histopathological abnormalities in the general male population, we
      examined gonads from 399 men 18 to 50 years old who died suddenly and
      unexpectedly. No sign of malignancy was found in any of these gonads. However, 3
      of the 399 men had been previously treated for testicular tumor or carcinoma in
      situ. Thus, the over-all prevalence of testicular neoplasia in the population
      studied was 0.8% (95% confidence limits 0.2 to 2.2%). This frequency is of the
      same magnitude as the lifetime risk of testicular cancer in the Danish male
      population. The median weights of the left and right testes were 19.3 and 19.7
      gm., respectively. This difference was statistically significant (p = 0.00003).
      Thus, our study confirmed that on average the left testis is smaller than the
      right testis. The median weight of the gonads collected in our study was 0.9 gm.
      lower than the weight of testes examined 40 years earlier at the same department
      of forensic medicine. However, this difference was not statistically significant
      (p = 0.17). Microscopic examination of the gonadal specimens revealed that 83% of
      the men exhibited complete spermatogenesis, including late spermatids in all
      tubules. In the age group studied we found no age-related changes in testicular
      weight or in the proportion of tubules with degenerative changes, such as
      spermatogenic arrest, the Sertoli-cell-only syndrome or hyalinization.

PMID- 1984106
TI  - Trace elements and urinary stone formation: new aspects of the pathological
      mechanism of urinary stone formation.
AB  - The urinary stone, serum and 24-hour urine concentrations of 14 trace elements
      were determined in urinary stone patients by inductively coupled plasma atomic
      emission spectroscopy. The data obtained for 25 active stone patients and 32
      whose last stone episode had occurred at least 12 months previously were compared
      with those of 25 healthy individuals. Urinary nickel, manganese and lithium
      excretion, and serum nickel, manganese and cadmium concentrations were
      statistically significantly lower for active stone patients compared to those
      with previous stone episodes and healthy individuals. No difference in the
      concentrations of trace elements could be found, however, for patients with
      previous stone episodes and healthy individuals. Nickel, manganese, lithium and
      cadmium could be of significance in the pathological mechanism of stone
      formation, not from mineralogical or crystallographic viewpoints but for the
      smooth flow of enzymatic reactions in biological systems.

PMID- 1984108
TI  - Learning the business of medicine.

PMID- 1984107
TI  - Clinical decision making: from theory to practice. Rationing by patient choice.

PMID- 1984109
TI  - Motherhood in medical school.

PMID- 1984110
TI  - Doctors and language: how we confuse our patients.

PMID- 1984111
TI  - Family matters.

PMID- 1984112
TI  - Cross-reactions among furosemide, hydrochlorothiazide, and sulfonamides.

PMID- 1984113
TI  - Carotid bruit audible to patient.

PMID- 1984114
TI  - New insights into how bacteria develop antibiotic resistance.

PMID- 1984115
TI  - Desert Shield makes history.

PMID- 1984116
TI  - 'Desirable weight' goes up in new guidelines.

PMID- 1984117
TI  - Where should the research dollars go?

PMID- 1984118
TI  - From the National Institutes of Health.

PMID- 1984119
TI  - From the Centers for Disease Control. AIDS in women--United States.

PMID- 1984120
TI  - Screening mammography.

PMID- 1984121
TI  - Selenium and breast cancer.

PMID- 1984122
TI  - Technology assessment and the fear of litigation.

PMID- 1984123
TI  - Consensus reports from the convinced: manipulating the information transfer
      process for drug promotion.

PMID- 1984124
TI  - A piece of my mind. Cold feet.

PMID- 1984125
TI  - Angioid streaks and pseudoxanthoma elasticum.

PMID- 1984126
TI  - The impact of nonclinical factors on repeat cesarean section.
AB  - Nonclinical factors, including the setting in which health care takes place,
      influence clinical decisions. This research measures the independent effects of
      organizational and socioeconomic factors on repeat cesarean section use in
      California. Of 45,425 births to women with previous cesarean sections in 1986,
      vaginal birth after cesarean section occurred in 10.9%. Sizable nonclinical
      variations were noted. By hospital ownership, rates ranged from 4.9% (for-profit
      hospitals) to 29.2% (University of California). Variations also existed by
      hospital teaching level (nonteaching hospitals, 7.0%, vs formalized teaching
      hospitals, 23.3%); payment source (private insurance, 8.1%, vs indigent services,
      25.2%); and obstetric volume (low-volume hospitals, 5.4%, vs high-volume
      hospitals, 16.6%). Multiple logistic regression demonstrated that these variables
      had independent effects after accounting for their overlapping influences and the
      effects of patient characteristics. The observed variations demonstrate the
      prominence of nonclinical factors in decision making and question the clinical
      appropriateness of current practice patterns.

PMID- 1984127
TI  - Barrier contraceptive methods and preeclampsia.
AB  - Recent investigations have suggested that women who use barrier methods of
      contraception may be at increased risk for preeclampsia. We used data from two
      prospective pregnancy studies to examine the relationship between contraceptive
      use before conception and preeclampsia. The preeclampsia rates among women using
      barrier contraceptives were not significantly higher than the rates in women
      using nonbarrier contraceptives or the rates in women using no contraceptives in
      either study. The odds ratios for preeclampsia in barrier contraceptive users in
      the two studies were 0.89 (95% confidence interval [Cl], 0.71 to 1.12) and 0.85
      (95% Cl, 0.49 to 1.45) compared with nonbarrier contraceptive users and 0.91 (95%
      Cl, 0.71 to 1.16) and 0.81 (95% Cl, 0.48 to 1.35) compared with women using no
      contraceptives. After adjusting for other risk factors, we found no association
      between preeclampsia and barrier contraceptive use. Additional studies are needed
      to resolve this issue; however, we would recommend that women not be advised to
      avoid barrier contraceptives unless more data linking their use to preeclampsia
      appear.

PMID- 1984128
TI  - Acute water intoxication as a complication of urine drug testing in the
      workplace.
AB  - Urine drug testing is now mandatory in many industries. We report the first case,
      to our knowledge, of an adverse consequence of drug testing in the workplace:
      acute water intoxication. We discuss normal water metabolism and the adverse
      effects of water loading and impaired renal function on free water clearance. We
      present a literature review of seven other cases of acute voluntary water
      intoxication in patients without chronic psychiatric or neurologic illness. For
      workers undergoing urine drug testing we conclude that risk factors for acute
      water intoxication include (1) intake of more than 1 L of water and (2) impaired
      urine dilution. In a recently drug-tested worker, symptoms of cerebral
      dysfunction should suggest the possibility of water intoxication.

PMID- 1984129
TI  - The variability of transfusion practice in coronary artery bypass surgery.
      Transfusion Medicine Academic Award Group.
AB  - We audited 540 patients undergoing elective first-time coronary artery bypass
      grafts at 18 institutions. The purposes of the study were to describe the
      variability in transfusions among institutions and to determine factors that may
      account for variability. Mean homologous red blood cell use per patient was
      2.9(+/- 0.1) U (institutional range, 0.4 to 6.3 U). One hundred seventy-seven
      patients (32%) received plasma (institutional range, 0% to 97%), and 119 (22%)
      received platelets (institutional range, 0% to 80%). After controlling for
      patient and surgical practice variables, transfusion practice factors still
      accounted for variation in red blood cell transfusions. Variation in patients
      receiving plasma and platelet transfusions among institutions was determined in
      part by prophylactic transfusions. We conclude that blood component usage for
      coronary artery bypass grafts differs widely among institutions. The variability
      in use of these components is accounted for in part by unnecessary transfusions
      in otherwise routine, uncomplicated coronary artery bypass graft procedures.

PMID- 1984130
TI  - Thrombotic thrombocytopenic purpura.

PMID- 1984131
TI  - Oral cobalamin for treatment of pernicious anemia?

PMID- 1984132
TI  - To treat the patient or to treat the surgeon.

PMID- 1984133
TI  - AHEC of a deal in south Texas.

PMID- 1984134
TI  - Key to organ donation may be cultural awareness.

PMID- 1984135
TI  - Hispanic HANES takes long look an latino health.

PMID- 1984136
TI  - COSSMHO trains community leaders.

PMID- 1984137
TI  - Desert Shield.

PMID- 1984138
TI  - From the Food and Drug Administration.

PMID- 1984139
TI  - From the Centers for Disease Control. Homicide among young black males--United
      States, 1978-1987.

PMID- 1984140
TI  - Development of emergency services in Costa Rica. A collaborative project in
      international health.

PMID- 1984141
TI  - A piece of my mind. Margo's logo.

PMID- 1984142
TI  - Toxoplasmosis testing during pregnancy.

PMID- 1984143
TI  - Pneumococcal vaccination: when in doubt, go ahead.

PMID- 1984144
TI  - Mycoplasma and epidemic group A meningococcal meningitis.

PMID- 1984145
TI  - It is OK to get sick in July.

PMID- 1984147
TI  - Crutch is sled and nothing's twisted in The Cider Mill.

PMID- 1984146
TI  - Denial and silent ischemia: which comes first?

PMID- 1984148
TI  - Does testing accelerate defibrillator failure?

PMID- 1984149
TI  - Chymopapain.

PMID- 1984150
TI  - Infant mortality among Hispanics. A portrait of heterogeneity.
AB  - In the United States, infant mortality risks among Hispanics have not been
      previously evaluated at the national level. We used the 1983 and 1984 national
      Linked Birth and Infant Death data sets to compare infant mortality risks among
      single-delivery infants of Hispanic descent with those among single-delivery
      infants of non-Hispanic whites (the reference group). We also included the 1983
      and 1984 linked birth cohort for single-delivery infants in Puerto Rico. Among
      all Hispanic groups, the neonatal (less than 28 days) mortality risk was higher
      among Puerto Rican islanders (relative risk [RR] = 2.3) and continental Puerto
      Ricans (RR = 1.5) and lower among Cuban-Americans (RR = 1.0) and Mexican
      Americans (RR = 1.0). The postneonatal mortality risk (28 to 364 days) was
      highest among continental Puerto Ricans (RR = 1.2) and lowest among Cuban
      Americans (RR = 0.6). Our study underscores the heterogeneity of the Hispanic
      population in the United States and suggests that interventions to prevent infant
      mortality be tailored to ethnic-specific risk factors and outcomes.

PMID- 1984151
TI  - Reproductive characteristics of Mexican-American, mainland Puerto Rican, and
      Cuban-American women Data from the Hispanic Health and Nutrition Examination
      Survey.
AB  - Data from the Hispanic Health and Nutrition Examination Survey were used to
      investigate reproductive characteristics of Hispanic females aged 15 to 45 years.
      Mexican-American and Puerto Rican women reported approximately 1.9 and 1.7 live
      births each, respectively, whereas Cuban-American women reported 1.1. Mexican
      American women were more likely to be using oral contraceptives and were more
      likely to have had a hysterectomy or an oophorectomy than were Cubans and Puerto
      Ricans. The largest percentage of tubal ligations were found among Puerto Rican
      women. Mexican women who had been pregnant in the previous 12 months were more
      likely than their Puerto Rican and Cuban-American counterparts to be
      breastfeeding. Further research is needed to investigate the decision processes
      and/or cultural variations that may be responsible for these differences in
      reproductive traits across national origin groups.

PMID- 1984152
TI  - Selected measures of health status for Mexican-American, mainland Puerto Rican,
      and Cuban-American children.
AB  - The 1987 National Vital Statistics System and the Hispanic Health and Nutrition
      Examination Survey (1982 through 1984) were used to assess the health status of
      Mexican-American, mainland Puerto Rican, and Cuban-American children by examining
      the prevalences of pregnancy outcomes and chronic medical conditions. The low
      birth-weight rate among Hispanics (7.0%) compared favorably with that of non
      Hispanic whites (7.1%) despite the greater poverty and lower levels of education
      among Hispanics. When examined by Hispanic subgroup, however, significant
      differences were present, with mainland Puerto Ricans having the highest
      prevalences of low-birth-weight infants. Premature births were more common among
      all three Hispanic subgroups than among non-Hispanic whites. Mexican-American and
      Cuban-American children had a similar prevalence of (3.9% and 2.5%, respectively)
      chronic medical conditions compared with non-Hispanic white children; Puerto
      Rican children had a higher prevalence of chronic medical conditions (6.2%). When
      assessed by these health status indicators, Hispanic children seem to have a
      health status similar to non-Hispanic white children. However, mainland Puerto
      Rican children seem at greater risk for poor health, reflecting the US Hispanic
      population's heterogeneity. Health programs targeted at US Hispanics should
      appropriately consider these group differences.

PMID- 1984153
TI  - Health insurance coverage and utilization of health services by Mexican
      Americans, mainland Puerto Ricans, and Cuban Americans.
AB  - This investigation examines data on 13,000 Mexican Americans, Puerto Ricans, and
      Cuban Americans between 6 months and 74 years of age who were interviewed from
      1982 through 1984 in the Hispanic Health and Nutrition Examination Survey. In
      addition, data from the 1989 Current Population Survey (N = 145,000) conducted by
      the US Bureau of the Census are presented for the white and black non-Hispanic
      populations as well as the three Hispanic national origin groups. The study
      revealed that over one third of the Mexican-American population, one fifth of the
      Puerto Rican population, and one fourth of the Cuban-American population is
      uninsured for medical expenditures compared with one fifth of the black, non
      Hispanic population and one tenth of the white, non-Hispanic population.
      Furthermore, compared with Hispanics with private health insurance, uninsured
      Hispanics are less likely to have a regular source of health care, less likely to
      have visited a physician in the past year, less likely to have had a routine
      physical examination, and less likely to rate their health status as excellent or
      very good.

PMID- 1984154
TI  - Access to health care for Hispanics.
AB  - The conventional population paradigm in the United States has distinguished
      between the white majority and the sizable and easily identified black minority.
      Until recently, much less attention has been paid to Hispanics (or Latinos),
      currently 20 million in number, who the Census Bureau projects will increase to
      31 million persons of a total population of 283 million by the year 2010. In the
      next two decades Hispanics will account for one of every three net additions to
      the US population. The analysis that follows considers the critical factors that
      collectively will determine the access of Hispanics to the health care system and
      illuminates the changes that, if introduced, will contribute to its improvement.
      These issues include the homogeneity or heterogeneity of the Hispanic population;
      the extent to which socioeconomic status adversely affects Hispanics' access to
      health care; the influence of demographic and epidemiological factors on their
      needs for care; the role of neighborhood factors in determining their access to
      the health and medical infrastructures; the paucity of Hispanic health
      professionals; and finally, the major reform proposals currently on the nation's
      health agenda as they relate to the issue of improved access to care for
      Hispanics.

PMID- 1984155
TI  - Health issues at the US-Mexican border.
AB  - With a rapidly growing population, increasing manufacturing activity, and
      increased interdependence, health issues on the US-Mexican border are demanding
      greater attention. It is unlikely that any other border in the world separates
      two nations having such variety in health status, entitlements, and utilization.
      Binational initiatives in the areas of environmental health and sanitation are
      clearly needed. Further cooperation between the United States and Mexico in
      provision of health services is warranted and will probably require enhanced
      federal funding or subsidies to be successful.

PMID- 1984156
TI  - Hispanic health in the United States. Council on Scientific Affairs.
AB  - Hispanics are the fastest growing minority in the United States. Typically, they
      are divided into five subgroups: Mexican American, Puerto Rican, Cuban American,
      Central or South American, and "other" Hispanics. Risk factors for morbidity and
      mortality vary among these subgroups. Use of health care services is affected by
      perceived health care needs, insurance status, income, culture, and language.
      Compared with whites, Hispanics are more likely to live in poverty, be unemployed
      or underemployed, and have little education and no private insurance. Hispanics
      are at an increased risk for certain medical conditions, including diabetes,
      hypertension, tuberculosis, human immunodeficiency virus infection, alcoholism,
      cirrhosis, specific cancers, and violent deaths. Proportionate to their
      representation in the population, there are few Hispanic health providers,
      emphasizing the need for all medical personnel to be knowledgeable about Hispanic
      health care needs.

PMID- 1984157
TI  - Hispanic health: time for data, time for action.

PMID- 1984158
TI  - Health status among Hispanics: major themes and new priorities.

PMID- 1984159
TI  - Angiographic follow-up after placement of a self-expanding coronary-artery stent.
AB  - BACKGROUND: The placement of stents in coronary arteries after coronary
      angioplasty has been investigated as a way of treating abrupt coronary-artery
      occlusion related to the angioplasty and of reducing the late intimal hyperplasia
      responsible for gradual restenosis of the dilated lesion. METHODS: From March
      1986 to January 1988, we implanted 117 self-expanding, stainless-steel
      endovascular stents (Wallstent) in the native coronary arteries (94 stents) or
      saphenous-vein bypass grafts (23 stents) of 105 patients. Angiograms were
      obtained immediately before and after placement of the stent and at follow-up at
      least one month later (unless symptoms required angiography sooner). The
      mortality after one year was 7.6 percent (8 patients). Follow-up angiograms
      (after a mean [+/- SD] of 5.7 +/- 4.4 months) were obtained in 95 patients with
      105 stents and were analyzed quantitatively by a computer-assisted system of
      cardiovascular angiographic analysis. The 10 patients without follow-up
      angiograms included 4 who died. RESULTS: Complete occlusion occurred in 27 stents
      in 25 patients (24 percent); 21 occlusions were documented within the first 14
      days after implantation. Overall, immediately after placement of the stent there
      was a significant increase in the minimal luminal diameter and a significant
      decrease in the percentage of the diameter with stenosis (changing from a mean
      [+/- SD] of 1.88 +/- 0.43 to 2.48 +/- 0.51 mm and from 37 +/- 12 to 21 +/- 10
      percent, respectively; P less than 0.0001). Later, however, there was a
      significant decrease in the minimal luminal diameter and a significant increase
      in the stenosis of the segment with the stent (1.68 +/- 1.78 mm and 48 +/- 34
      percent at follow-up). Significant restenosis, as indicated by a reduction of
      0.72 mm in the minimal luminal diameter or by an increase in the percentage of
      stenosis to greater than or equal to 50 percent, occurred in 32 percent and 14
      percent of patent stents, respectively. CONCLUSIONS: Early occlusion remains an
      important limitation of this coronary-artery stent. Even when the early effects
      are beneficial, there are frequently late occlusions or restenosis. The place of
      this form of treatment for coronary artery disease remains to be determined.

PMID- 1984160
TI  - The effect of epilepsy or diabetes mellitus on the risk of automobile accidents.
AB  - BACKGROUND: Previous studies of possible associations between chronic medical
      conditions and traffic safety have been inconsistent and subject to bias because
      of the incomplete identification of affected persons. Recent advances in the
      diagnosis and management of epilepsy and diabetes mellitus have improved the
      control of these disorders and suggest a need to reexamine the risk of traffic
      mishaps among patients with these conditions. METHODS: We conducted a population
      based retrospective cohort study of 30,420 subjects 16 to 90 years of age, with
      and without epilepsy or diabetes mellitus. Subjects included all the licensed
      drivers in seven contiguous ZIP Code areas in which the Marshfield Clinic and St.
      Joseph's Hospital, Marshfield, Wisconsin, are the primary sources of medical
      care. Standardized rates of moving violations and accidents over a four-year
      period (1985 through 1988) were compared in affected and unaffected cohorts.
      RESULTS: Standardized mishap ratios for subjects with diabetes were 1.14 for all
      moving violations (P = 0.23) and 1.32 for accidents (P = 0.01); for subjects with
      epilepsy the ratios were 1.13 for moving violations (P = 0.26) and 1.33 for
      accidents (P = 0.04). CONCLUSIONS: We conclude that drivers with epilepsy or
      diabetes mellitus have slightly increased risks of traffic accidents as compared
      with unaffected persons. The increases in risk observed in our study were
      generally smaller than those in previous studies, and we believe they are not
      great enough to warrant further restrictions on driving privileges.

PMID- 1984161
TI  - The clinical importance of acquired abnormalities of platelet function.

PMID- 1984162
TI  - Liver transplantation for type IV glycogen storage disease.

PMID- 1984163
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 1-1991. A 45-year-old man with HIV infection, an epidural mass,
      and a history of treated pulmonary tuberculosis and a seminoma.

PMID- 1984164
TI  - Coronary-artery stents and other endoluminal devices.

PMID- 1984165
TI  - Health status and motor vehicle crashes.

PMID- 1984166
TI  - Continuing lessons from glycogen storage diseases.

PMID- 1984167
TI  - Risk of exposure of surgical personnel to patients' blood.

PMID- 1984168
TI  - Treatment of anemia associated with multiple myeloma.

PMID- 1984169
TI  - Remission of hyperprolactinemia after pregnancy.

PMID- 1984170
TI  - Relation of cholesterol level to cardiovascular mortality among men with and
      without preexisting cardiovascular disease.

PMID- 1984171
TI  - Population screening for the cystic fibrosis gene.

PMID- 1984172
TI  - Stealth steroids.

PMID- 1984173
TI  - Trekker's shoulder--an old diagnosis.

PMID- 1984174
TI  - The "doctor's letter"--what is our obligation?

PMID- 1984175
TI  - A cluster of Rhodococcus (Gordona) Bronchialis sternal-wound infections after
      coronary-artery bypass surgery.

PMID- 1984176
TI  - A cluster of legionella sternal-wound infections due to postoperative topical
      exposure to contaminated tap water.

PMID- 1984177
TI  - Chewing the fat--how much and what kind?

PMID- 1984179
TI  - Biology and management of bladder cancer.

PMID- 1984178
TI  - Surgical-wound infection.

PMID- 1984180
TI  - Hepatitis B virus DNA and RNA in primary liver cancer.

PMID- 1984181
TI  - Transfusion-associated graft-versus-host disease.

PMID- 1984182
TI  - Chronic Lyme arthritis and HLA alleles.

PMID- 1984183
TI  - Failure of mefloquine prophylaxis in east Africa.

PMID- 1984184
TI  - Rapid gastric emptying in patients with early non-insulin-dependent diabetes
      mellitus.

PMID- 1984185
TI  - Correction--echocardiography.

PMID- 1984186
TI  - Chemistry in the kitchen. Making ground meat more healthful.
AB  - BACKGROUND: The National Cholesterol Education Program recommends a diet
      containing less than 30 percent of calories in the form of fat, less than 10
      percent in the form of saturated fat, and less than 300 mg of cholesterol per
      day. Since Americans' diets generally exceed these recommendations, we wished to
      find an easy kitchen method to reduce substantially saturated fat and cholesterol
      in ground meat. METHODS: Raw ground meat was heated in vegetable oil and rinsed
      with boiling water to extract fat and cholesterol. The fat-free broth was
      recombined with the meat to restore flavor. The amounts of total fat, saturated
      fat, and cholesterol in the meat after extraction were compared with the amounts
      in meat cooked as patties and in stir-fried, rinsed meat. RESULTS: When raw
      ground beef containing 9.6 to 20.8 percent fat was cooked as patties and the fat
      poured off, 6 to 17 percent of the fat and 1.3 to 4.3 percent of the cholesterol
      were lost. In stir-fried, rinsed ground beef, 23 to 59 percent of the fat and 9.0
      to 18.8 percent of the cholesterol were lost. When vegetable oil was used to
      extract fat and cholesterol from beef containing 20.7 percent fat, a mean (+/-
      SD) of 67.7 +/- 1.6 percent of the fat and 39.2 +/- 5.1 percent of the
      cholesterol were lost. The differences between conventionally cooked meat and
      meat prepared by the extraction of fat were significant (P less than 0.001). An
      average of 43 percent (range, 38 to 49) of cholesterol was extracted from a wide
      variety of ground meats. Although conventional cooking produced no change in
      fatty-acid composition as compared with raw meat, our extraction process greatly
      increased the ratio of unsaturated to saturated fat, from 1.32 in conventionally
      cooked meat to 2.92 to 4.56 in meat after extraction. Extraction resulted in the
      loss of 72 to 87 percent of saturated fat. CONCLUSIONS: This method produces a
      tasty meat product that is much lower in saturated fat and cholesterol than
      conventionally cooked meat, and that can be used in sauces, soups, and solid meat
      products.

PMID- 1984187
TI  - Effect of restricting dietary protein on the progression of renal failure in
      patients with insulin-dependent diabetes mellitus.
AB  - BACKGROUND: Restriction of dietary protein may slow the progression of renal
      failure in diverse renal diseases, but the extent to which such a diet is
      beneficial in patients with diabetic nephropathy is uncertain. METHODS: We
      studied the effect of reduced intake of protein and phosphorus on the progression
      of renal disease in 35 patients with insulin-dependent (Type I) diabetes mellitus
      and clinically evident nephropathy. The low-protein, low-phosphorus diet
      contained 0.6 g of protein per kilogram of ideal body weight per day, 500 to 1000
      mg of phosphorus, and 2000 mg of sodium. The control diet consisted of the
      patient's prestudy diet with the stipulation that it contain 2000 mg of sodium
      and at least 1 g of protein per kilogram per day and 1000 mg of phosphorus. Renal
      function was assessed by measurement of iothalamate and creatinine clearances at
      intervals of 3 to 6 months, and the patients were followed for a minimum of 12
      months (mean, 34.7). The declines in mean glomerular filtration rates were
      compared between groups by linear-regression analysis of the glomerular
      filtration rate as a function of time. RESULTS: The patients who followed the
      study diet for a mean of 37.1 months had declines in iothalamate clearance of
      0.0043 ml per second per month and in creatinine clearance of 0.0055 ml per
      second per month. The comparable values in the control group were 0.0168 and
      0.0135, respectively (P less than 0.05). Blood pressure was well controlled, and
      the degree of glycemic control was comparable in both groups. CONCLUSION: Dietary
      restriction of protein and phosphorus can retard the progression of renal failure
      in patients with Type I diabetes mellitus who have nephropathy. We believe that
      wider use of this treatment is indicated.

PMID- 1984188
TI  - Familial occurrence of inflammatory bowel disease.
AB  - BACKGROUND AND METHODS: We assessed the familial occurrence of inflammatory bowel
      disease in Copenhagen County, where there has been a long-term interest in the
      epidemiology of such disorders. In 1987 we interviewed 662 patients in whom
      inflammatory bowel disease had been diagnosed before 1979, asking whether their
      first- and second-degree relatives had this disorder. Ninety-six percent of the
      patients (504 with ulcerative colitis and 133 with Crohn's disease) provided
      adequate information. RESULTS: As compared with the general population, the first
      degree relatives of the 637 patients with ulcerative colitis or Crohn's disease
      had a 10-fold increase in the risk of having the same disease as the patients,
      after standardization for age and sex. The risk of having the other of the two
      diseases was also increased, but less so, and the increase in the risk of having
      Crohn's disease was not significant in the relatives of patients with ulcerative
      colitis. The risk of ulcerative colitis in first-degree relatives of patients
      with ulcerative colitis appeared to be virtually independent of the generation to
      which the first-degree relative belonged and of the sex of the patient and the
      relative. The risk of ulcerative colitis in first-degree relatives tended to be
      higher if the disease had been diagnosed in the patient before the age of 50, but
      the risk seemed to be independent of the current age of the relatives. The
      prevalence of the same disease as that of the patient (either ulcerative colitis
      or Crohn's disease) among second-degree relatives was increased; the prevalence
      of the other disease was not increased. CONCLUSIONS: The 10-fold increase in the
      familial risk of ulcerative colitis and Crohn's disease strongly suggests that
      these disorders have a genetic cause.

PMID- 1984189
TI  - Medical malpractice--the Canadian experience.

PMID- 1984190
TI  - Gonadotropin-releasing hormone and its analogues.

PMID- 1984191
TI  - Aldosterone synthesis in salt-wasting congenital adrenal hyperplasia with
      complete absence of adrenal 21-hydroxylase.
AB  - BACKGROUND: Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is a
      disorder of cortisol and aldosterone biosynthesis that results from mutations in
      the CYP21 gene encoding the adrenal 21-hydroxylase P-450c21. It can cause severe
      salt wasting in newborns that requires long-term treatment with glucocorticoids
      and mineralocorticoids. We describe a spontaneous partial recovery from this
      disorder in a 19-year-old woman who had discontinued treatment. METHODS: We
      measured plasma and urinary levels of adrenal hormones, plasma renin activity,
      and sodium balance longitudinally in the patient and four other patients in whom
      adrenal hyperplasia had been diagnosed in infancy and in whom DNA analysis had
      predicted a complete absence of functional P-450c21. The ratio of plasma renin
      activity to urinary aldosterone was used as a measure of the response of the
      adrenal zona glomerulosa. Two patients underwent intravenous infusion of
      [3H]progesterone for the measurement of extraadrenal production of 21
      hydroxylated precursors of aldosterone. RESULTS: The patient who had discontinued
      her medication excreted a normal amount of aldosterone (20.0 nmol per square
      meter of body-surface area per day) while following a diet low in sodium. Her
      ratio of plasma renin activity to urinary aldosterone-18-glucuronide excretion
      was 1.7 after three days of sodium restriction, as compared with a ratio of 4.7
      at the age of nine years (normal range, 0.03 to 0.1). The percentage of
      extraadrenal conversion of progesterone to deoxycorticosterone was low. The four
      other patients had variable responses to sodium restriction after the neonatal
      period (range for plasma renin activity:urinary aldosterone-18-glucuronide, 1.9
      to 19.4). CONCLUSIONS: Although patients with salt-wasting 21-hydroxylase
      deficiency have functionally equivalent mutations in their CYP21 genes, they may
      vary from one another and over time in their ability to produce
      mineralocorticoids. This variation may be attributable to another adrenal enzyme
      with 21-hydroxylase activity.

PMID- 1984192
TI  - A randomized study of the effect of withdrawing hydroxychloroquine sulfate in
      systemic lupus erythematosus.
AB  - BACKGROUND: The antimalarial drug hydroxychloroquine is thought to be effective
      in controlling some of the manifestations of systemic lupus erythematosus, but
      its effectiveness has not been demonstrated conclusively. METHODS: We conducted a
      six-month, randomized, double-blind, placebo-controlled study of the effect of
      discontinuing hydroxychloroquine sulfate treatment in 47 patients with clinically
      stable systemic lupus erythematosus. The patients were randomly assigned to
      continue their same dose of hydroxychloroquine (n = 25) or to receive placebo (n
      = 22) for 24 weeks. Ten patients in each group were also taking prednisone.
      RESULTS: The relative risk of a clinical flare-up, defined as the development of
      specific clinical manifestations of systemic lupus erythematosus or an increase
      in their severity, was 2.5 times higher (95 percent confidence interval, 1.08 to
      5.58) in the patients taking placebo than in those continuing to take
      hydroxychloroquine (16 of 22 patients vs. 9 of 25 had flare-ups), and the time to
      a flare-up was shorter (P = 0.02). The relative risk of a severe exacerbation of
      disease that required withdrawal from the study was 6.1 times higher (95 percent
      confidence interval, 0.72 to 52.44) for the patients taking placebo (5 of 22
      patients vs. 1 of 25 had severe exacerbations of disease). Changes in the dose of
      prednisone were not different in the two groups. CONCLUSIONS: Patients with
      quiescent systemic lupus erythematosus who are taking hydroxychloroquine are less
      likely to have a clinical flare-up if they are maintained on the drug.

PMID- 1984193
TI  - An epidemiologic study of abuse of analgesic drugs. Effects of phenacetin and
      salicylate on mortality and cardiovascular morbidity (1968 to 1987)
AB  - BACKGROUND: Phenacetin abuse is known to produce kidney disease; salicylate use
      is supposed to prevent cardiovascular disease. We conducted a prospective,
      longitudinal epidemiologic study to examine the effects of these drugs on cause
      specific mortality and on cardiovascular morbidity. METHODS: In 1968 we evaluated
      a study group of 623 healthy women 30 to 49 years old who had evidence of a
      regular intake of phenacetin, as measured by urinary excretion of its
      metabolites, and a matched control group of 621 women. Salicylate excretion was
      also measured. All subjects were examined over a period of 20 years. RESULTS:
      Life-table analyses of mortality during the 20 years, with adjustment for the
      year of birth, cigarette smoking, and length of follow-up, revealed significant
      differences between the groups in overall mortality (study group vs. control
      group, 74 vs. 27 deaths; relative risk, 2.2; 95 percent confidence interval, 1.5
      to 3.3), deaths due to urologic or renal disease (relative risk, 16.1; 95 percent
      confidence interval, 3.9 to 66.1), deaths due to cancer (relative risk, 1.9; 95
      percent confidence interval, 1.1 to 3.3), and deaths due to cardiovascular
      disease (relative risk, 2.9; 95 percent confidence interval, 1.5 to 5.5). The
      relative risk of cardiovascular disease (fatal or nonfatal myocardial infarction,
      heart failure, or stroke) was 1.8, and the 95 percent confidence interval 1.3 to
      2.6. The odds ratio for the incidence of hypertension was 1.6, and the 95 percent
      confidence interval 1.2 to 2.1. The effects of phenacetin on morbidity and
      mortality, with adjustment for base-line salicylate excretion, were similar. In
      contrast, salicylate use had no effect on either mortality or morbidity.
      CONCLUSIONS: Regular use of analgesic drugs containing phenacetin is associated
      with an increased risk of hypertension and mortality and morbidity due to
      cardiovascular disease, as well as an increased risk of mortality due to cancer
      and urologic or renal disease. The use of salicylates carries no such risk.

PMID- 1984195
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 3-1991. A 17-year-old boy with autoimmune hemolytic anemia and
      abnormal liver function.

PMID- 1984194
TI  - Glucose-6-phosphate dehydrogenase deficiency.

PMID- 1984196
TI  - Therapy for systemic lupus erythematosus.

PMID- 1984197
TI  - The risks of phenacetin use.

PMID- 1984198
TI  - Rationing medical care.

PMID- 1984199
TI  - Asbestos-related diseases.

PMID- 1984200
TI  - Lack of efficacy of hydergine in Alzheimer's disease.

PMID- 1984201
TI  - Transplacental passage of insulin.

PMID- 1984202
TI  - Neural-tube defects and derangement of homocysteine metabolism.

PMID- 1984203
TI  - Positron-emission tomographic scanning of primary and metastatic breast carcinoma
      with the radiolabeled glucose analogue 2-deoxy-2-[18F]fluoro-D-glucose.

PMID- 1984204
TI  - Drinking and flying.

PMID- 1984205
TI  - A strategy to reduce infant mortality.
AB  - Using maternal mortality reviews as an historic model, fetal and infant mortality
      reviews are proposed to reduce infant mortality in the United States. The
      national program has three elements: 1) guidelines and direction from a national
      multidisciplinary steering panel and staff, 2) a technical advisory capacity to
      translate guidelines and to work with local and regional review committees, and
      3) local review committees. A special emphasis, lacking in the limited efforts of
      previous infant mortality reviews, would be given to fetal mortality. The plan
      proposes a broad classification of potential contributing causes of mortality,
      from those related strictly to medical care, to the health system, and to
      individual patient factors. This will allow different and more effective targeted
      responses to factors identified locally. Critical impetus will be gained with The
      American College of Obstetricians and Gynecologists leading the effort from the
      private medical sector in partnership with national, state, and local public
      health agencies and other national medical societies.

PMID- 1984206
TI  - Umbilical artery Doppler velocimetry as a labor admission test.
AB  - Doppler ultrasound of the umbilical artery flow velocity waveform was studied
      prospectively as an admission test at the labor ward. Recordings were made in 575
      women in various stages of labor before, during, and after uterine contractions,
      and evaluated in relation to intrapartum and fetal outcome variables. No
      association was found between abnormal flow velocity waveforms and cord
      complications, meconium-stained amniotic fluid, or abnormal fetal heart rate
      tracing, nor was there any association with operative delivery for fetal distress
      or low Apgar scores at 1 and 5 minutes. Small for gestational age fetuses had
      significantly more abnormal flow velocity waveforms than appropriate for
      gestational age fetuses, and so had those with umbilical artery acidemia compared
      with those with normal pH. The results indicate that Doppler recording of the
      umbilical artery flow velocity waveform as an admission test at the labor ward is
      not a good predictor of fetal distress in an unselected population.

PMID- 1984207
TI  - Direct measurement of intracellular free calcium in cultured human puerperal
      myometrial cells stimulated by oxytocin: effects of extracellular calcium and
      calcium channel blockers.
AB  - The changes in intracellular free calcium concentration ([Ca2+]i) induced by
      oxytocin in single cells of cultured human puerperal myometrium were measured
      with the calcium-sensitive fluorescent dye fura 2 in a digital imaging
      fluorescence microscopic system. Oxytocin at concentrations of 30-300 nmol/L
      induced a dose-dependent increase in [Ca2+]i with a peak at 20 seconds. This
      increase depended mainly on extracellular calcium ([Ca2+]ex) at concentrations of
      0.6-4.8 mmol/L. In the absence of [Ca2+]ex, the increase was only 16% of that in
      its presence. The voltage-sensitive calcium channel blockers nicardipine,
      nifedipine, and nitrendipine had similar effects, causing significant suppression
      of the increase in [Ca2+]i induced by oxytocin. Diltiazem also suppressed the
      increase in [Ca2+]i, though less than the other calcium channel blockers. These
      data indicate that the increase in [Ca2+]i induced by oxytocin is predominantly
      dependent upon [Ca2+]ex. Furthermore, the data explain why calcium channel
      blockers are effective for weakening uterine muscle contractions and indicate
      which type of blocker is most effective.

PMID- 1984208
TI  - Human T-cell leukemia virus type I infection as an oncogenic and prognostic risk
      factor in cervical and vaginal carcinoma.
AB  - The seroprevalence of human T-cell leukemia virus type I (HTLV-I) antibody in
      6701 healthy females and 226 women with gynecologic malignancies, all living in
      an adult T-cell leukemia-endemic area in southwestern Japan, was investigated to
      determine whether HTLV-I infection was a risk factor influencing oncogenesis and
      prognosis. The seroprevalences in cervical carcinoma patients younger than 59
      years and in vaginal carcinoma patients of all ages were significantly higher
      than in age-matched healthy controls. The ratios of observed to expected HTLV-I
      seroprevalence in patients younger than 59 with cervical carcinoma and in vaginal
      carcinoma patients were 2.92 and 7.36, respectively. Among the patients with
      cervical carcinoma or vaginal carcinoma, the tumor recurrence rate in HTLV-I
      carriers was significantly higher than that in HTLV-I seronegative patients. Our
      results suggest that HTLV-I infection may be oncogenic and may affect the
      prognosis in some patients with cervical or vaginal carcinoma.

PMID- 1984209
TI  - Appendectomy in primary and secondary staging operations for ovarian malignancy.
AB  - Appendectomy was performed at primary or secondary staging operations in 100
      patients with ovarian malignancies. Of 80 patients who underwent appendectomy at
      the time of their primary surgery, 25 (31.2%) had appendiceal metastases. Among
      47 patients who were believed to have disease limited to the pelvis at the time
      of surgery--stage I (N = 34), II (N = 7), IIIA (N = 5), and those designated
      stage IIIC solely on the basis of microscopic para-aortic nodal metastasis (N =
      1)--the appendix was involved with disease in only two patients (4.3%). However,
      among 33 patients with advanced disease--stage IIIB (N = 6), IIIC except those
      designated IIIC solely on the basis of microscopic paraaortic nodal metastasis (N
      = 19), and IV (N = 8)--the appendix was involved with disease in 23 patients
      (69.7%) (P less than .001). Poorly differentiated tumors and serous histologic
      cell types more frequently metastasized to the appendix (64, 15, 6, and 8% for
      grades 3, 2, and 1 and borderline histology, respectively; P less than .001; and
      48, 13, and 8% for serous, endometrioid, and mucinous; P less than .001). Of 20
      patients who underwent appendectomy at their secondary staging procedure, two had
      metastases. Metastatic disease in the appendix was microscopic in nine of 27
      patients. Because the frequency of appendiceal metastasis is similar to that of
      other metastatic sites in stages I and II ovarian cancer, it should be removed at
      primary staging procedures. Appendectomy should also be performed in patients
      with advanced ovarian malignancies if it contributes to cytoreduction or at the
      time of secondary staging procedures.

PMID- 1984211
TI  - Infertility-associated endometrial cancer risk may be limited to specific
      subgroups of infertile women.
AB  - Data from previous studies suggest that infertility is a risk factor for
      endometrial cancer. We used data from the Cancer and Steroid Hormone Study to
      further characterize this relationship. The subject group comprised 399 women
      ages 20-54 with newly diagnosed epithelial endometrial cancer ascertained through
      six cancer registries. The control group comprised 3040 women in the same age
      range selected by random-digit telephone dialing from the same geographic areas
      where cancer patients resided. Compared with women who reported no fertility
      problem, women with physician-diagnosed infertility who had reported at least 2
      years of infertility had an odds ratio for endometrial cancer, adjusted for age,
      of 1.7 (95% confidence interval 1.1-2.6). Women who reported infertility
      resulting from ovarian factors had an adjusted odds ratio of 4.2 (95% confidence
      interval 1.7-10.4). These results suggest that factors such as anovulation may
      explain much of the increased risk of endometrial cancer found among subgroups of
      infertile women.

PMID- 1984210
TI  - Clinical and pathologic correlation of endometrial cavity fluid detected by
      ultrasound in the postmenopausal patient.
AB  - A registry of ultrasound procedures spanning nearly 5 years was searched
      retrospectively to discover cases of endometrial cavity fluid collections in
      postmenopausal women. Twenty cases were identified; all medical records were
      available for review. One patient was lost to follow-up. Seventeen patients had
      surgical procedures: 11 had only a D&C, and six had a primary evaluation of
      laparotomy with removal of the uterus and adnexa. Five women had cancer (two
      ovarian, one tubal, one endometrial, and one cervical); eight women had benign
      gynecologic conditions, including uterine fibroids (five), ovarian serous
      cystadenoma (two), and cervical dysplasia (one). There were two cases of apparent
      subclinical pyometra. Five women had endometrial pathology consistent with
      prescribed hormone therapy for breast cancer (four) or endometrial hyperplasia
      (one).

PMID- 1984212
TI  - Persistent trophoblast after conservative treatment of tubal pregnancy:
      prediction and detection.
AB  - The incidence of persistent trophoblast and risk of second surgical intervention
      after conservative treatment of tubal pregnancy are substantial. The preoperative
      and postoperative hCG patterns in patients with tubal pregnancy were studied to
      see whether this information could predict and detect persistent trophoblast at
      an early stage. Ninety-eight women with tubal pregnancy underwent conservative
      surgical treatment by laparoscopy or laparotomy. Eight developed postoperative
      complications necessitating a second operation, and seven of them had both
      biochemical and histologic evidence of persistent trophoblastic activity. In
      seven of 31 patients with preoperative hCG above 3000 IU/L, a second operation
      was necessary, whereas in 67 with preoperative hCG levels below 3000 IU/L, only
      one such intervention was necessary. Eight of the 22 patients with hCG above 1000
      IU/L on the second day after surgery and seven of 11 patients with hCG above 1000
      IU/L on the seventh day after surgery later needed a second surgical procedure.
      In contrast, 86 of 87 women with hCG below 1000 IU/L on the seventh day after
      surgery had an uneventful convalescence. We conclude that pre- and postoperative
      hCG measurements can identify patients at risk of developing persistent
      trophoblast. Further, in patients with preoperative hCG titers below 3000 IU/L,
      we recommend conservative surgery followed by measurement of hCG 1 week
      postoperatively.

PMID- 1984213
TI  - Cocaine abuse is associated with abruptio placentae and decreased birth weight,
      but not shorter labor.
AB  - Many of our patients report having ingested cocaine hoping to decrease the
      duration of labor. We reviewed the computerized records of 592 women who abused
      cocaine. Compared with 4687 controls, women who ingested cocaine were older and
      had higher parity. Birth weight, birth weight percentile, and gestational age at
      delivery were significantly decreased among their neonates, and the incidence of
      abruptio placentae was nearly doubled among these women. Although these factors
      tend to shorten labor, the total duration of labor was not significantly
      different between the two groups. These data add to the accumulating evidence
      that cocaine abuse is associated with increased obstetric morbidity, but do not
      support the belief that cocaine shortens labor.

PMID- 1984214
TI  - Tightening the ship.

PMID- 1984215
TI  - Nonpharmaceutical ripening of the unfavorable cervix and induction of labor by a
      novel double balloon device.
AB  - Artificial ripening of the unfavorable cervix was attempted in 48 women using
      intracervical prostaglandin (PG) E2 gel applied by a cannula and in 70 others by
      a newly designed double balloon device (Atad Ripener Device). In the first group
      (phase A), application of PGE2 gel by intracervical cannula resulted in a mean
      increase of 3 points in the Bishop score and a mean instillation-to-delivery time
      of 34.2 hours. The study of labor induction by the double balloon device was
      carried out in two parts. One (phase B) consisted of a double-blind randomized
      controlled study in which, through the double balloon device, ten women received
      PGE2 gel and another ten were given placebo gel. There was no significant
      difference in the increase of Bishop score between the two groups (5.8 points in
      the treatment group and 6.0 in the placebo-controlled group). Ninety percent of
      women in both groups delivered vaginally with a mean of 20.8 hours after device
      insertion. The third phase of the study consisted of an open trial of inserting
      the double balloon device alone without PGE2, and inflating the balloons in 50
      patients. A mean increase of 4.4 points in the Bishop score was noted in these
      women. These findings suggest that the use of the double balloon device for
      ripening of the unfavorable cervix is an effective and well-tolerated method of
      labor induction.

PMID- 1984216
TI  - Ambulatory blood pressure monitoring during pregnancy: validation of the TM-2420
      monitor.
AB  - To validate the accuracy of the TM-2420 ambulatory blood pressure monitor in
      pregnant women, its measurements were compared with those taken simultaneously by
      two trained observers using a random zero sphygmomanometer. Each of 30 pregnant
      women had her blood pressure measured three times. The mean differences between
      the monitor and the averaged observer measurements were -0.53 +/- 2.7 mmHg for
      systolic blood pressure, -5.4 +/- 5.3 mmHg for Korotkoff phase 4 (P less than
      .001), and 0.87 +/- 3.7 mmHg for phase 5 diastolic blood pressure. The TM-2420
      ambulatory monitor provides reliable estimates of systolic and Korotkoff phase 5
      diastolic blood pressures during pregnancy.

PMID- 1984217
TI  - Transcatheter arterial embolization in the management of postpartum hemorrhage
      due to genital tract injury.
AB  - Six patients with uncontrollable postpartum hemorrhage due to genital tract
      injury were treated with transcatheter arterial embolization. The causes of
      hemorrhage were laceration of the cervix and vagina in five cases and rupture of
      the uterus in one. Four cases included a large hematoma in the paravaginal and/or
      retroperitoneal space. Two women had a hysterectomy before arterial embolization.
      Angiography revealed extravasation in five cases. All six subjects had their
      hemorrhage arrested dramatically using transcatheter arterial embolization with
      gelatin sponge particles. No major complication was encountered in any case.
      Normal menstruation resumed in the women who did not undergo a hysterectomy.
      Transcatheter arterial embolization therapy seems to be the treatment of choice
      in patients with uncontrollable hemorrhage.

PMID- 1984218
TI  - Fetal blood sampling from the intrahepatic vein: analysis of safety and clinical
      experience with 214 procedures.

PMID- 1984219
TI  - The clinical significance of blood transfusion at the time of radical
      hysterectomy.

PMID- 1984220
TI  - Home uterine activity monitoring is associated with a reduction in preterm birth.

PMID- 1984221
TI  - Maternal, uteroplacental, and fetoplacental hemodynamic and Doppler velocimetric
      changes during epidural anesthesia in normal labor.
AB  - Pulsed Doppler and M-mode maternal echocardiography were combined with uterine
      and umbilical artery Doppler velocimetry to characterize the hemodynamic changes
      associated with fluid preload and epidural anesthesia in 12 normal laboring
      gravidas at term. Fluid preload alone was associated with significant (P less
      than .05) increases in heart rate (11%), stroke volume (10%), and cardiac output
      (20%), and a decrease in systemic vascular resistance (19%). There were no
      changes in mean arterial pressure (MAP) or ejection fraction during any stage of
      the study. Following placement of the epidural block, stroke volume and cardiac
      output returned to values not significantly different from baseline, whereas
      heart rate remained elevated and systemic vascular resistance remained decreased.
      There were no changes in uterine or umbilical artery systolic-diastolic (S-D)
      ratios during any stage of the study. We conclude that fluid preload and epidural
      anesthesia cause significant changes in maternal cardiac output, heart rate,
      stroke volume, and systemic vascular resistance without affecting MAP. These
      maternal changes do not correlate with any changes in uterine or umbilical artery
      S-D ratios following epidural anesthesia in the normal laboring gravida.

PMID- 1984222
TI  - The effects of epidural anesthesia on the Doppler velocimetry of umbilical and
      uterine arteries in normal and hypertensive patients during active term labor.
AB  - To study the effects of epidural anesthesia on uterine and umbilical artery blood
      flow in preeclampsia, we observed 25 patients in active labor at 36 or more
      weeks' gestation. Seven had preeclampsia, eight had chronic hypertension, and ten
      had no complications. Doppler velocimetry of the uterine and umbilical arteries
      was performed before and after intravenous fluid loading and at 30 and 60 minutes
      after epidural blockade. Maternal vital signs and fetal heart rate were monitored
      continuously. After epidural block, mean maternal blood pressure fell
      significantly in all groups, but no maternal hypotension was observed. Mean
      maternal and fetal heart rates were unchanged. After epidural block, mean uterine
      artery systolic-diastolic (S-D) ratios did not change in the chronic-hypertension
      and normal groups, but fell significantly in the preeclamptic group to values
      similar to those of the normal group. Umbilical artery S-D ratios did not change
      in any group. In preeclamptic pregnancy, epidural anesthesia may help to reduce
      uterine artery vasospasm and may benefit intrapartum fetal well-being.

PMID- 1984223
TI  - Imaging the fetal brain in the second and third trimesters using transvaginal
      sonography.
AB  - High-frequency transvaginal probes were used at 20-40 weeks' gestation to develop
      a systematic examination of the fetal brain. Modeling the procedure after the
      standard neonatal neurosonographic examination, we attempted to obtain three
      coronal sections (anterior, midline, posterior) and two sagittal sections
      (midsagittal, right or left parasagittal). In 70 normal patients, all planes were
      imaged with a similar frequency (74-76%) except for the posterior coronal plane,
      which was imaged 59% of the time. Among the first 35 cases, 17% had a complete
      study, compared with 71% of the second 35 cases. Transvaginal sonography
      established or changed the diagnosis in five of the 13 cases with central nervous
      system or other abnormalities. We recommend that a complete fetal
      neurosonographic examination include transvaginal sonography to complement and
      enhance the transabdominal examination, especially for cases in which a fetal
      abnormality is suspected.

PMID- 1984224
TI  - The effect of age on female fecundity.
AB  - To determine the relationship between age and female fecundity, 210 women were
      studied prospectively. The subjects had negative infertility evaluations and were
      receiving therapeutic donor insemination. Life-table analysis was performed on
      751 donor insemination cycles. For comparison, patients were divided into five
      separate age groups and into two separate groups, ages 19-34 and 35-45. Monthly
      fecundity and cumulative conception rates were calculated for each group. A
      significant difference was found when all age groups were compared (P = .05) and
      when those at or above age 35 and those below age 35 were compared (P less than
      .05). Frozen semen was used in 92% of all cycles. The average monthly fecundity
      of all patients treated with frozen semen was 16%. This study confirms a
      progressive decline in fecundity with age in a completely evaluated group of
      women undergoing therapeutic donor insemination and demonstrates that frozen
      semen can yield acceptable fecundity provided sufficient numbers of motile sperm
      are used for each procedure.

PMID- 1984225
TI  - Successful use of gamete intrafallopian transfer does not reverse the decline in
      fertility in women over 40 years of age.
AB  - To assess the impact of assisted reproductive technologies on the potential
      fertility of older women, we report our experience with gamete intrafallopian
      transfer (GIFT) in a large number of women 40 years of age and older. One hundred
      twenty-two GIFT cycles were initiated in 59 women over 18 months. Seventy-three
      tubal transfers were performed, resulting in seven clinical pregnancies, a rate
      of 9.6% per transfer. This contrasts with a 27.3% clinical pregnancy rate per
      transfer in women under 40. Thus, older patients require thorough counseling
      regarding the decreased likelihood of success despite the use of assisted
      reproductive technologies.

PMID- 1984226
TI  - Poloxamer 407 as an intraperitoneal barrier material for the prevention of
      postsurgical adhesion formation and reformation in rodent models for reproductive
      surgery.
AB  - Comtemporary adhesion-prevention regimens for infertility surgery emphasize the
      use of barrier materials to effect physical separation of injured surfaces before
      reperitonealization. Poloxamer 407 is a biocompatible polymer that displays
      reverse thermal gelation characteristics; that is, the material exists as a
      liquid at room temperature and as a solid at body temperature. These properties
      make it an ideal material for use in laparoscopic surgery. The antiadhesion
      properties of poloxamer 407 were evaluated in two models. In the first
      experiment, Golden hamsters were subjected to a standardized adhesion-producing
      lesion in the left uterine horn. Poloxamer solutions in concentrations ranging
      from 15-35% were applied to the injured horn. Location, thickness, and extent of
      adhesion formation were assessed 14 days later. Significant reduction in post
      traumatic adhesion formation was observed following treatment with the 30-35%
      solutions. The second experiment was designed as a paradigm of the typical
      situation encountered in infertility surgery: prevention of adhesion reformation
      after lysis of established adhesions. New Zealand White rabbits were subjected to
      three laparotomies at 14-day intervals for placement of the adhesion-producing
      lesion, evaluation (prescore) and surgical lysis of induced adhesions, and
      subsequent evaluation of adhesion reformation (post-score). The effect of
      applying poloxamer 407 after adhesiotomy was compared with controls (no
      treatment). Adhesion reformation (post-score) was markedly reduced by poloxamer
      407 treatment. Further trials of this material in the clinical setting are
      indicated.

PMID- 1984227
TI  - Stability of immunoreactive beta-core fragment of hCG.
AB  - The beta core fragment of hCG (beta C-hCG) accounts for a large proportion of hCG
      immunoreactivity in the urine of pregnant women. It is often increased in the
      urine of patients with gynecologic tumors and may become an important diagnostic
      tool in early pregnancy and cancers. Despite the importance of beta C-hCG, little
      is known about its stability in urine under conditions of differing pH and
      temperature. This study examined the effect of repeated freeze-thaw cycles;
      storage at room temperature, 4C, and -20 C over several months; and the effect of
      alteration of urine pH. The two specific immunoassays for beta C-hCG used do not
      significantly cross-react with intact hCG or the free alpha subunit. Despite
      different cross-reactivities of the antibodies to the free beta subunit and
      higher immunoactivity when the radioimmunoassay was used, there was excellent
      correlation between the two assays in pregnancy urine. This suggests that there
      is little free beta subunit in urine from pregnant women. In addition, this study
      evaluated the stability of intact hCG and beta-hCG under identical conditions. No
      alterations in their immunoactivities were found under most conditions of
      storage. It is concluded that, for clinical purposes, beta C-hCG as well as
      intact hCG and free beta subunit are very stable molecules.

PMID- 1984228
TI  - Third-trimester fetal death in triplet pregnancies.
AB  - During the last decade, 89 sets of triplets were born in Denmark with a
      gestational age of more than 25 completed weeks. Fifteen pregnancies (16.9%) were
      complicated by fetal death in the third trimester, with a total of 17
      intrauterine deaths. Six neonatal deaths occurred, leaving 22 survivors among
      these 15 patients. Four triplet gestations were diagnosed as twins until
      delivery. Eight women conceived spontaneously, two gestations followed assisted
      fertilization and embryo transfer, and five women had had various forms of
      ovulation stimulation. The mean maternal age was 27.8 years (range 17-38). Seven
      women were parous and eight wer nulliparous. Maternal complications included
      hydramnios (three), preeclampsia/hypertension (three), and anemia (nine). All
      women delivered preterm. Of the 11 gestations diagnosed as triplets, fetal death
      was diagnosed at 32.2 +/- 2.9 weeks (mean +/- SD) and delivery occurred at 32.6
      +/- 3.0 weeks. Nine of 11 women had cesarean deliveries. Continuation of
      pregnancy after fetal death could be considered in only three subjects. In eight
      women, obstetric reasons required immediate delivery. Fetal death was associated
      with monochorionic or dichorionic placentation, and growth retardation was a
      frequent complication before fetal death. Anencephaly of one fetus, umbilical
      cord problems in two, and severe hydrops in two were the only obvious causes of
      fetal death. Fetal death should not be the sole indication for delivery. In cases
      with severe prematurity and a stable intrauterine situation, frequent assessments
      of fetal well-being are recommended, with prompt delivery when indicated.

PMID- 1984229
TI  - A randomized, double-blind, placebo-controlled trial of oral antibiotic therapy
      following intravenous antibiotic therapy for postpartum endometritis.
AB  - One hundred thirty-six patients were enrolled in a randomized, double-blind,
      placebo-controlled trial of oral antibiotic therapy (amoxicillin) versus placebo
      following successful intravenous (IV) antibiotic therapy for postpartum
      endometritis. No subjects were readmitted to the hospital for recurrent
      endometritis and there were no wound infections or recurrent fevers. Minor side
      effects were seen in 10% of those taking amoxicillin and 14% of those taking
      placebo. Compliance was fair; only 52% of those taking amoxicillin and 65% of
      those taking placebo completed therapy. The lack of infectious complications in
      this high-risk population suggests that oral antibiotic therapy is unnecessary
      after successful IV antibiotic therapy for endometritis.

PMID- 1984230
TI  - Factors associated with postpartum hemorrhage with vaginal birth.
AB  - A case-control study was performed to study risk factors for postpartum
      hemorrhage. Cases of hemorrhage were defined by a hematocrit decrease of 10
      points or more between admission and post-delivery or by the need for red-cell
      transfusion. Patients with antenatal bleeding were excluded. Among 9598 vaginal
      deliveries, postpartum hemorrhage occurred in 374 cases (3.9%). Three controls
      were matched to each case and multiple logistic regression was used to control
      for covariance among predictor variables. Factors having a significant
      association with hemorrhage were prolonged third stage of labor (adjusted odds
      ratio 7.56), preeclampsia (odds ratio 5.02), mediolateral episiotomy (4.67),
      previous postpartum hemorrhage (3.55), twins (3.31), arrest of descent (2.91),
      soft-tissue lacerations (2.05), augmented labor (1.66), forceps or vacuum
      delivery (1.66), Asian (1.73) or Hispanic (1.66) ethnicity, midline episiotomy
      (1.58), and nulliparity (1.45). These data may help predict postpartum hemorrhage
      and may be useful in counseling patients about the advisability of home delivery,
      intravenous access in labor, or autologous blood donation.

PMID- 1984231
TI  - Factors associated with hemorrhage in cesarean deliveries.
AB  - A case-control study was performed to study risk factors for hemorrhage in
      cesarean deliveries. Hemorrhage was defined by a pre- to post-delivery hematocrit
      decrease of 10 points or more or by the need for red-cell transfusion. Patients
      with antenatal bleeding were excluded. Among 3052 cesarean deliveries, hemorrhage
      occurred in 196 cases (6.4%). Three controls were matched to each case and
      multiple logistic regression was used to control for covariance among predictor
      variables. Factors having a significant association with hemorrhage were: general
      anesthesia (adjusted odds ratio 2.94), amnionitis (odds ratio 2.69), preeclampsia
      (2.18), protracted active phase of labor (2.40), second-stage arrest (1.90), and
      Hispanic ethnicity (1.82). After adjustment for these variables, a classic
      uterine incision had a small but significant association (odds ratio 1.06) with
      hemorrhage. Previous cesarean, parity, gestational age, and several other factors
      had no association with hemorrhage. These data allow one to anticipate hemorrhage
      in patients at risk and may be useful in planning appropriate use of blood bank
      resources, including antepartum autologous blood donation.

PMID- 1984232
TI  - Reduced frequency of hypertensive disorders in placenta previa.
AB  - The isthmic segment of the uterine artery's ascending branch has a freer course
      and wider diameter than distal parts of the vessel. Therefore, we assumed that
      this arterial segment would provide better blood flow and prevent hypoxia of the
      trophoblast. As a result, placenta previa pregnancies would be complicated by
      hypertensive disorders less often than are pregnancies with normally implanted
      placentas. To test this hypothesis, 491 placenta previa pregnancies, among a
      population of 106,866 pregnant women, were compared with pregnancies with
      normally implanted placentas. Clinically meaningful and statistically significant
      reductions in the rates and risks of hypertensive disorders were found in
      placenta previa pregnancies (P = .002, relative risk = 0.44, 95% confidence
      interval 0.25-0.78). The differences persisted when primiparous and multiparous
      women were examined separately and when preterm and term deliveries were
      separated. In a multivariate logistic regression analysis, patients with placenta
      previa had a third of the risk for hypertensive disorders compared with pregnant
      women with normally implanted placentas (relative risk = 0.36, 95% confidence
      interval 0.20-0.64), even after controlling for parity and preterm or term
      delivery. In the same model, primiparity and preterm delivery were each
      associated with a doubling of risk for hypertensive disorders, regardless of the
      placental implantation site. Thus, regardless of parity and preterm or term
      delivery, placenta previa and hypertensive disorders are inversely related.

PMID- 1984233
TI  - Patient experience in a diabetic program project improves subsequent pregnancy
      outcome.
AB  - There has been a notable improvement in the outcome of the pregnancies of insulin
      dependent diabetics. This improvement has resulted from intensive health care
      programs and increased awareness among patients and health providers of the need
      for specialized prenatal care. We hypothesized that participation in a
      specialized program providing early glycemic control would benefit the patient's
      subsequent pregnancy, despite progression of the diabetic disease process. We
      prospectively studied 55 insulin-dependent diabetic patients enrolled before 9
      weeks' gestation through two consecutive pregnancies: sequence 1 and sequence 2.
      A control group of 55 insulin-dependent diabetic patients, entering the program
      for the first time, were matched with the sequence 2 pregnancies of the study
      group by maternal age and year of pregnancy. Specific outcomes related to
      glycemic control in early gestation were significantly improved from sequence 1
      to sequence 2 pregnancies: earlier week of entry (P = .0001), lower
      glycohemoglobin at 9 weeks (P = .005) and at 14 weeks (P = .02), and improved
      fetal outcome (decreased rate of spontaneous abortions or major malformations; P
      less than .01). Week of entry and glycohemoglobin at 9 and 14 weeks were also
      significantly improved compared with the control group. Seventy-three percent of
      the patients entered the program earlier in their sequence 2 pregnancies (P =
      .001) and had lower glycohemoglobin concentrations at 9 weeks (P = .005) compared
      with their sequence 1 pregnancies. Sixty-five percent of the patients in sequence
      2 had advanced diabetic disease (White class D-RF), compared with 46% in sequence
      1 (P less than .05) and 44% of the controls (P less than .05).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1984234
TI  - Haemophilus influenzae: an important cause of maternal and neonatal infections.
AB  - Although Haemophilus influenzae is recognized as a major pathogen of infants, its
      role in maternal and neonatal infections is not as well appreciated. We analyzed
      the records of all mothers and neonates infected with H influenzae over a 10-year
      period. Twenty-eight mother/neonate sets were identified in which at least one
      had documented infection with H influenzae. Of the 18 mothers with documented
      infection, 13 had chorioamnionitis, endometritis, or both, and two of these
      mothers were bacteremic with H influenzae. Of the 23 infected neonates, 15
      presented with early sepsis and/or pneumonia and nine had conjunctivitis. During
      the period of the study, only group B streptococci and Escherichia coli were more
      common as causes of early neonatal bacteremia. Under the conditions of this
      retrospective study, maternal infection predicted neonatal infection. However,
      prospective studies in which asymptomatic patients are cultured will be required
      to determine how well maternal colonization/infection with H influenzae predicts
      neonatal infection.

PMID- 1984235
TI  - Comparison of culture for group B streptococcus versus enzyme immunoassay and
      latex agglutination rapid tests: results in 250 patients during labor.
AB  - Two hundred fifty women in labor were screened for vaginal colonization by group
      B streptococcus using standard culture and two rapid tests. This primarily
      Hispanic population had a group B streptococcus vaginal colonization rate of 2.4%
      (95% confidence interval 0.9-5.2%) for the patients sampled. An enzyme
      immunoassay and a latex agglutination test for group B streptococcus antigen both
      had sensitivities of 33% and had specificities of 99 and 95%, respectively, when
      compared with culture. Neither rapid test appeared to be clinically useful for
      detecting colonized women in labor, although both can be useful in excluding
      colonization.

PMID- 1984236
TI  - Amiodarone pulmonary toxicity: morphologic and biochemical features.

PMID- 1984237
TI  - The effect of pyruvate or dihydroxyacetone on parenterally induced liver lipid
      accumulation in the rat.
AB  - Orally fed pyruvate (pyr) and dihydroxyacetone (DHA) have been shown to decrease
      liver lipid accumulation in animal models. These compounds lessen the degree of
      fatty liver in ethanol-fed rats and in a genetic strain of hens predisposed to
      fatty liver. Total parenteral nutrition can result in liver dysfunction,
      including fatty infiltration of the liver. In this study, rats were assigned to
      either control, pyr, or DHA groups. All rats were fitted with jugular vein
      catheters, and following a 3-day recovery, were infused continuously for 7 days.
      The infusate provided adequate nutrition (including 7% kcal as fat) with 5% pyr
      or 5% DHA (g/liter) substituted for dextrose in the experimental groups. Plasma
      triglycerides were lower in the pyr groups relative to controls: 62.2 +/- 34.7
      (SE) vs 96.8 +/- 44.3 mg/dl, though this was significant only at P less than
      0.10. Neither pyr nor DHA decreased liver lipids. Pyr and DHA were administered
      intravenously in this study, and therefore passed through the heart and to
      peripheral tissues first. These compounds may need to be fed orally, passing via
      the portal system, to produce the liver lipid-lowering effects seen in other
      studies.

PMID- 1984238
TI  - Preliminary studies on the indium slide immunoassay for estimation of human
      chorionic gonadotropin and antihuman chorionic gonadotropin antibody.
AB  - Human chorionic gonadotropin (hCG) is synthesized and secreted as early as 170 hr
      after fertilization and has been used as an index for pregnancy. Neutralization
      of hCG with a beta-subunit hCG vaccine(s) has been proposed as a contraceptive
      technique. To monitor the duration of effectiveness of the vaccine, it will be
      necessary to monitor the anti-hCG antibodies, especially those responsible for
      inhibiting the hCG bioactivity. We report a simple, rapid technique using an
      indium slide immunoassay for the qualitative estimation of hCG and to monitor a
      bioeffective anti-hCG antibody. The sensitivity of the indium slide assay to
      measure hCG ranged from 1 microgram/ml to 1 ng/ml, depending on the format of the
      assay. The indium slide assay also detected anti-hCG antibodies generated against
      a specific determinant on hCG recognized by a neutralizing monoclonal antibody
      (P3W80) in women immunized with a contraceptive vaccine.

PMID- 1984239
TI  - Nonenzymatic glycation of collagen in aging and diabetes.
AB  - Considerable progress has been made in our understanding of nonenzymatic
      glycation of collagen, and the relationship between glycation of collagen and
      changes in connective tissue associated with aging and diabetes. Recent studies
      surveyed in this review suggest the following conclusions: 1. Collagen content of
      early glycation products does not appear to increase throughout the life span in
      normal human subjects, although small increases may occur that are linked to
      glycemic changes. These products are increased, relative to age-matched controls,
      in experimental diabetes and in diabetes mellitus in collagen from virtually all
      tissues analyzed. 2. Collagen content of browning products increases with aging
      and appears to be higher in diabetic subjects than in age-matched controls. Rates
      of accumulation may be accelerated in subpopulations of diabetic subjects at high
      risk for developing complications. 3. Increases in early glycation products do
      not appear to be associated with alterations in collagen solubility, thermal
      rupture time, or mechanical strength, nor is there an association with most
      diabetic complications. Alterations in these products may, however, affect
      conformation, ligand binding, lysyl oxidase-mediated cross-linking, and
      interactions between collagen and other macromolecules in the extracellular
      matrix. 4. Increased content of browning products is associated with many
      physicochemical changes in collagen as well as with long-term complications in
      diabetes mellitus. 5. Regulatory mechanisms have been identified in vivo that may
      serve to control or limit the formation of glycation products. 7. Pharmacologic
      agents have been identified that may be able to reduce collagen content of late
      glycation products. Despite the progress that has been made in this field, many
      areas of uncertainty and controversy exist. For example, there is not yet a
      consensus that the browning products associated with collagen exclusively
      comprise advanced Maillard products derived from nonenzymatically glycated
      residues. There is evidence that oxidative reactions involving lipids also play a
      role in generating fluorophores and chromophores that may alter properties of
      collagen. Thus, in the extracellular matrix collagen may be continuously modified
      by at least three very different processes: Maillard reactions, interactions with
      oxidizing lipids, and enzymatically mediated cross-linking. The
      interrelationships between these and possibly other posttranslational
      modifications remain a poorly understood area of great complexity.

PMID- 1984240
TI  - Determination of superoxide dismutase activity by the polarographic method of
      catalytic currents in the cerebrospinal fluid of aging brain and neurologic
      degenerative diseases.
AB  - The activity of the superoxide dismutase was measured by the polarographic method
      of catalytic currents in the cerebrospinal fluid of patients with age-related
      neurologic degenerative diseases, namely, amyotrophic lateral sclerosis and
      Alzheimer's disease, and of a reference group of normal subjects. The superoxide
      dismutase activity was found to increase with age in reference subjects (r =
      0.81) while no significant correlation was found in amyotrophic lateral sclerosis
      and Alzheimer's disease patients. The activity mean values were significantly
      lower (P less than 0.01) in patients with neurologic degenerative diseases than
      in the reference subjects. The changes of superoxide dismutase activity in the
      aging brain and in age-related neurologic degenerative diseases are discussed.

PMID- 1984241
TI  - Intrahypothalamic pituitary grafts elevate prolactin in the cerebrospinal fluid
      and attenuate prolactin release following ether stress.
AB  - Anterior pituitary (AP) tissue grafted into the hypothalamus of female rats
      inhibits the luteotrophic prolactin (PRL) secretion which normally follows
      mating. Dopamine blockade has been shown to overcome this inhibition, suggesting
      that the grafts suppress PRL release from the in situ pituitary by the action of
      graft PRL increasing dopamine activity in the hypothalamus. To examine whether
      PRL levels in the cerebrospinal fluid (CSF) were elevated by the AP grafts, CSF
      samples were taken from 5 control rats and 10 rats bearing intrahypothalamic AP
      grafts. Mean PRL concentrations in the CSF of the control rats were 3.0 +/- 0.8
      ng/ml. The grafted rats had significantly higher concentrations of PRL in their
      CSF, averaging 23.2 +/- 4.2 ng/ml (P less than 0.005). Plasma PRL concentrations
      were similar in the control and grafted rats. PRL release in response to 5 min of
      ether stress was examined in 8 control and 11 grafted rats. In control animals,
      PRL rose from 4.2 +/- 1.5 to 44.7 +/- 9.0 ng/ml following exposure to ether, but
      the response was significantly attenuated in the grafted rats, peaking at 9.3 +/-
      1.4 ng/ml (P less than 0.001). This inhibition of response due to the grafts was
      evident within 1 week of graft placement. The results confirm that the presence
      of intrahypothalamic AP grafts led to the accumulation of supranormal PRL
      concentrations in the CSF. This elevated PRL suppressed pituitary PRL release in
      response to ether stress, probably by an autoregulatory feedback activation of
      the inhibitory tuberoinfundibular dopaminergic neurons in the hypothalamus.

PMID- 1984242
TI  - Intestinal brush border calcium uptake in spontaneously hypertensive rats and
      their genetically matched WKY rats.
AB  - The current studies were designed to characterize calcium transport by intestinal
      brush border membrane in the spontaneously hypertensive rat (SHR) and
      normotensive control, the Wistar-Kyoto (WKY) rat. The biochemical and functional
      purity of the intestinal brush border membranes in SHR and WKY rats was validated
      by marker enzymes and the ability to transiently transport D-glucose in the
      presence of Na+ gradient. Calcium transport into duodenal and jejunal vesicles
      represented a minor binding component and transmembrane movement as evident by
      initial rate studies, A23187 studies, and lanthanum displacement experiments.
      Initial rate and time course of calcium uptake was lower in SHR compared with WKY
      rats. Kinetic analysis of calcium uptake by the jejunum (total uptake minus
      binding component) showed a Vmax of 6.98 +/- 0.2 and 1.8 +/- 0.2 nmol/mg
      protein/7 sec in WKY rats and SHR, respectively (P less than 0.001), whereas Km
      values were 0.76 +/- 0.04 and 0.87 +/- 0.1 mM for WKY rats and SHR, respectively.
      Similar kinetic analysis of calcium uptake by the duodenal segments showed a Vmax
      of 10.3 +/- 0.8 and 2.8 +/- 0.2 nmol/mg protein/7 sec in WKY rats and SHR,
      respectively (P less than 0.01). Km values were 0.7 +/- 0.2 and 0.3 +/- 0.06 mM
      (P greater than 0.05). Vmax of calcium uptake in the 2-week-old rats
      (prehypertensive period) was 6.0 +/- 0.3 and 3.53 +/- 0.3 nmol/mg protein/7 sec
      in WKY rats and SHR, respectively (P less than 0.001), whereas Km values were
      0.60 +/- 0.07 and 0.5 +/- 0.01 mM, respectively. These results suggest that
      calcium binding and uptake by duodenal and jejunal intestinal brush border
      membranes of SHR is significantly decreased compared with WKY rats. The decrease
      in transmembrane calcium uptake is secondary to decrease in Vmax and is present
      before the appearance of hypertension, implying a genetically determined defect
      in calcium uptake in intestinal brush border membranes of the SHR.

PMID- 1984243
TI  - Oxygen transport and peripheral microcirculation in long-term diabetes.
AB  - The purpose of this investigation was to evaluate the impact of long-term
      diabetes on muscle blood flow (MBF) and oxygen transport (vO2) during exercise.
      Twelve male patients (58 +/- 8 years, mean +/- SD), with at least a 10-year
      history of diabetes controlled by insulin, and seven age-matched controls (56 +/-
      5 years, mean +/- SD) participated in this study. No patient had been clinically
      diagnosed as having peripheral vascular disease, and on the average resting
      ankle/arm systolic blood pressure ratios were normal. Following a baseline
      period, 5 min of cycle ergometer exercises at 75 W were performed in the upright
      position and, after 1-hr recovery, in the supine position. Continuous vO2 was
      determined via breath-by-breath analysis. MBF was measured in the vastus
      lateralis (VL) and tibialis anterior (TA) by 133Xe clearance. In the erect
      position, the diabetic group (compared with the control group, respectively)
      exhibited significantly (P less than 0.05) lower exercise MBF [ml. (100 g.min)-1]
      in both VL (19 +/- 2.5 vs 30.9 +/- 2) and TA (13.7 +/- 2 vs 22.0 +/- 4), a lower
      steady-state VO2 (1.3 +/- 0.3 vs 1.7 +/- 0.2 liters.min-1) during exercise
      including the values in the last 15 sec of exercise, and greater accumulation of
      blood lactate (35 +/- 2 vs 22.0 +/- 2 mg/100 ml). The same trends in the data
      were observed during supine exercise; however, the blood pressure of the
      diabetics was significantly elevated during exercise when compared with that of
      controls. The reduced exercise MBF in the TA and VL demonstrated that impaired
      microvascular flow, without clinically overt peripheral vascular disease, in long
      term diabetics leads to reduced oxygen delivery and exercise tolerance.

PMID- 1984245
TI  - Manganese, copper, zinc, and iron concentrations and subcellular distribution in
      two types of skeletal muscle.
AB  - To clarify trace element distribution in red and white muscle, and to verify two
      populations of muscle mitochondria, the iron, zinc, copper, and manganese
      concentrations of whole muscle and their subcellular fractions were determined.
      The iron, zinc, copper, and manganese concentrations of red muscle were 1.83,
      4.31, 2.05, and 1.67 times higher than those of white muscle, respectively. In
      skeletal muscle subcellular distribution or iron, zinc, and copper were entirely
      different and that of manganese was relatively similar as compared with those in
      liver reported previously. The pattern of mineral distribution in all fractions
      of red muscle was similar to that of white muscle, but their concentrations in
      some fractions were different between red and white muscle, e.g., iron, zinc, and
      manganese in supernatant fraction and copper in nuclear and microsomal fractions.
      The difference between subsarcolemmal and interfibrillar mitochondria were
      ascertained by the distribution of trace elements.

PMID- 1984244
TI  - Enhancement of antibody production by lysophosphatidylcholine and alkylglycerol.
AB  - Inflammation products of normal and cancerous tissues, lysophosphatidylcholine
      and dodecylglycerol, were tested for their adjuvant effect on the antibody
      response. Mice treated with these agents and immunized with sheep erythrocytes
      simultaneously or at 3 days posttreatment developed a greatly enhanced antibody
      production as demonstrated by the Jerne plaque assay. Mice immunized at 3 days
      postadministration of agents did not significantly produce enhanced antibody
      secreting cells as compared with those of mice simultaneously immunized. Since
      the mechanism of macrophage activation by lysophospholipids requires contribution
      of B and T cells, BALB/c-nu/nu mice treated with these agents and subsequently
      immunized with sheep erythrocytes did not produce antibodies. However,
      conditioned medium of in vitro-treated BALB/c-nu/nu B cells efficiently
      transmitted a signal to untreated BALB/c +/+ T cells for enhanced macrophage
      ingestion activity. This observation suggests that lysophospholipid-activated
      macrophages and T cells efficiently transmitted antigenic signal to the antibody
      producing B cell population. Therefore, we conclude that these lipid metabolites
      have dual beneficial effects for the host by enhancing phagocytosis and antibody
      production. Thus, lysophosphatidylcholine and dodecylglycerol have potential
      practical application as adjuvants that could be administered separately or in
      combination with antigens.

PMID- 1984246
TI  - Lactational [correction of Lacational] anovulation in rats and its dependency on
      progesterone.
AB  - The relationship between prolactin (PRL) secretion and anovulation in lactating
      rats was studied. Normal lactating rats and lactating rats treated with antiserum
      against luteinizing hormone-releasing hormone at the time of postpartal ovulation
      were used. Normal lactating rats were treated with either a dopamine agonist (CB
      154, 150 micrograms/rat) on Day 10 or 13, or pups removal on Day 7 or 10, and
      thereafter luteolysis and inhibition on PRL secretion were assessed. With the CB
      154 treatment, the incidence of luteolysis increased as the lactational period
      advanced (42% vs 72%), whereas it decreased (73% vs 14%) with the pups removal.
      Thus, dopamine effectively inhibited PRL secretion during the later lactational
      stage, but could not do so during the earlier stage when there were mechanisms
      other than dopamine stimulating PRL secretion. Following luteal regression
      induced by CB-154, ovulation did not occur if the rats were treated with CB-154
      on Day 10, whereas 50% of the rats ovulated within 4 days if treated on Day 13.
      Furthermore, in the lactating rats treated with anti-luteinizing hormone
      releasing hormone serum during late pregnancy, ovulation was not observed until
      Day 10 of lactation. Since the serum progesterone levels were low in these rats
      due to the absence of ovulation and lactational corpora lutea, the blockade of
      ovulation was not due to elevated circulating progesterone during the early
      lactational period. The mechanism of ovulation blockade during lactation thus
      seems to shift from being progesterone independent to progesterone dependent at a
      similar period when the neuroendocrine control of PRL secretion shifts from
      dopamine independent to dependent.

PMID- 1984247
TI  - The price of maturity.

PMID- 1984248
TI  - Stereotyping between physical therapy students and occupational therapy students.
AB  - The purpose of this study was to examine the existence of preprofessional
      stereotypes in physical therapy (PT) and occupational therapy (OT) students at an
      urban midwestern university. Forty-two junior PT students and 42 junior OT
      students completed the Health Team Stereotyping Scale (HTSS) as a self
      administered survey questionnaire. The students' total and individual word-pair
      scores on the HTSS were then compared. The first comparison, between the PT
      students' and the OT students' views of the PT profession, indicated that the PT
      students' assessment of the PT profession was more positive than that of the OT
      students. The second comparison, between the OT students' and the PT students'
      views of the OT profession, indicated that the OT students' perception of the OT
      profession was more positive than that of the PT students. Each student group
      chose both positive and negative descriptors for the other group. Some positive
      adjectives chosen by the OT students to describe PT students were "proud,"
      "passive," and "precise." The PT students chose "casual" and "intentional" to
      positively describe OT students. Some negative adjectives chosen by the OT
      students to describe PT students were "overrated," "competitive," and "strict."
      The PT students described OT students as "passive," "dull," and "narrow." Both
      groups thought the other group was conventional and conservative. Awareness of
      the existence of positive and negative stereotypes may influence behaviors in
      preprofessional and professional environments.

PMID- 1984250
TI  - A new challenge--robotics in the rehabilitation of the neurologically motor
      impaired.
AB  - Rehabilitation robotics is a research area, originating in engineering, that has
      emerged in the last decade. Its broad aim is to use robot technology to assist
      people with movement dysfunction. The neurologically impaired population might
      gain considerably from the provision of robots as "assistants" or "therapy
      aides," but the interface with the machine must match both the physical and
      intellectual abilities of the user. We therefore consider a multidisciplinary
      approach, encompassing both behavioral and engineering perspectives, to be
      essential in achieving this aim. However, to date, published reports have been
      largely restricted to engineering journals or conference reports, and relatively
      little has appeared in the therapy literature. This article seeks to introduce
      physical therapists to robotics, describe possible applications to the
      rehabilitation of neurologically impaired patients, and suggest issues deserving
      further investigation.

PMID- 1984249
TI  - Electromyographic and cinematographic analysis of movement from a kneeling to a
      standing position in healthy 5- to 7-year-old children.
AB  - Physical therapists often use transitional postures such as half-kneeling to help
      children with movement dysfunction attain an upright posture. Little is known,
      however, about how healthy children activate lower extremity muscles to move the
      hip, knee, and ankle joints as they move from kneeling through half-kneeling to
      stand up against gravity. The purpose of this study was to describe movement from
      kneeling to standing in 10 healthy 5- to 7-year-old children. Electromyography
      was used to record the activity of four lower extremity muscles. Cinematography
      was used to record joint motion of the hip, knee, and ankle of the leg initiating
      movement, in addition to trajectories of specific anatomical landmarks as the
      children rose from a kneeling to a standing position. Greater active range of
      motion of the hip, knee, and ankle was necessary to move from a kneeling to a
      standing position using the half-kneel transitional posture than is required
      during normal gait. The activation patterns of the gastrocnemius, tibialis
      anterior, rectus femoris, and biceps femoris muscles of the leg initiating
      movement exhibited variability among subjects during the kneel-to-stand movement.
      Maximum joint range of motion and position of the hip, knee, and ankle joints at
      specific points in the movement exhibited less variability than patterns of
      muscle activation. The results showed that movement from a kneeling to a standing
      position in healthy children is quantifiable and can be used to help determine
      what normal components of movement are necessary to successfully master this
      movement against gravity that is antecedent to ambulation. Further studies are
      needed to investigate antigravity movement in younger children and in children
      with movement dysfunction to more fully understand normal and abnormal movement
      in children.

PMID- 1984251
TI  - Brain potentials associated with movement in traumatic brain injury.
AB  - Brain potentials may be used to assess the functional abnormalities that underlie
      impairments of movement. The purpose of this article is to illustrate the
      usefulness of examining these potentials. In addition to an overview of the
      topic, the article includes a report of a study demonstrating that there were
      differences between the brain potentials of five patients with traumatic brain
      injury and those of four healthy control subjects. All five patients were in the
      postacute phase of hemiplegia. Slow cortical potentials associated with simple
      goal-directed forearm and finger movements were recorded from frontal and
      parietal electrodes. Two seconds of movement-related electroencephalographic
      activity (movement-related potential) were recorded. The patients showed reduced
      brain potentials for movements associated with their paretic limb and, to a
      lesser extent, reduced brain potentials for movements associated with their
      nonparetic limb. The waveforms obtained from the patients were unusual, with
      uncharacteristic cross-cortical movement-related potential correlations
      associated with specific electrode configurations, as well as with specific
      movement conditions. Brain potentials associated with the fore-period interval of
      a simple reaction time paradigm were later recorded in two of the patients with
      traumatic brain injury and in a control subject to help determine the functional
      significance of the relative positivity apparent in their movement-related
      potential data. This preliminary study indicates that electroencephalographic
      potentials obtained during the preparation for and execution of movement can
      provide information regarding the basis for motor dysfunction.

PMID- 1984252
TI  - Regression of local and distant tumor growth by tissue expansion: an experimental
      study of mammary carcinoma 13,762 in rats.

PMID- 1984253
TI  - Continuous versus conventional tissue expansion: experimental verification of a
      new technique.
AB  - Historically, tissue expansion is a prolonged process, typically requiring at
      least 6 weeks to complete. Recently, interest has increased in shortening this
      time period. In the current study, a continuous infusion device maintaining
      constant expander pressure less than capillary filling pressure was used in a
      canine model in seven dogs to minimize the time period needed to achieve
      significant expansion. There were no complications, except one device
      malfunction, corrected by changes in design. The process was shown to be a safe
      and effective means of producing amounts of expansion similar to traditional
      methods in approximately 72 hours, with expansion of 28 percent (n = 6) for
      continuous tissue expansion (CTE) versus 34 percent (n = 6) for a 2-week rapid
      expansion protocol. This expansion was derived from either stretch of preexisting
      tissue (46 percent for CTE, 35 percent for 2-week expansion) or recruitment of
      adjacent tissue. The clinical application of continuous tissue expansion could
      permit the advantages of tissue expansion to be obtained in many more situations
      than are currently available to traditional tissue expansion techniques.

PMID- 1984254
TI  - Prefabrication of composite free flaps through staged microvascular transfer: an
      experimental and clinical study.
AB  - The feasibility of prefabricating free flaps by inducing, through the process of
      staged reconstruction, an arteriovenous bundle and its surrounding fascia to
      perfuse a selected block of tissue was investigated experimentally and
      clinically. Sixteen rat knee joints were wrapped with their ipsilateral
      superficial inferior epigastric (SIE) fascia. In 8 joints, the composite flaps
      were resected en bloc and were immediately replaced orthotopically pedicled upon
      the superficial inferior epigastric vessels. In the remaining joints, the
      resection and orthotopic transfer were performed 2 weeks later. Only the joints
      in the latter group, which benefited from the staging period, were found to be
      perfused. The long finger proximal interphalangeal joint of a child was
      reconstructed by the staged microvascular transfer of his second toe proximal
      interphalangeal joint. At the first stage, a temporalis fascia flap was wrapped
      around the toe proximal interphalangeal joint and revascularized to the dorsalis
      pedis vessels. Six weeks later, the joint and its temporalis fascia envelope were
      dissected, and the "prefabricated" joint flap was transferred to the hand and
      revascularized to the wrist vessels. Bony union progressed uneventfully with
      excellent recovery of the range of motion. We conclude that regardless of the
      indigenous vascular anatomy, an unlimited array of composite free flaps can be
      constructed and transferred based on induced large vascular pedicles.

PMID- 1984255
TI  - Split-thickness skin grafting of the myelomeningocele defect: a subset at risk
      for late ulceration.
AB  - The appropriate method and timing of the management of the myelomeningocele
      defect have prompted considerable discussion. Use of split-thickness skin grafts
      acutely has accomplished wound closure with low morbidity and mortality. This
      study was designed to address the question of long-term suitability of the
      technique of split-thickness skin grafting of the myelomeningocele patient. The
      incidence of late and/or severe skin ulceration and the presence of gibbus
      deformity were correlated with the method of skin closure. Long-term follow-up
      revealed a higher incidence of chronic skin ulceration in the split-thickness
      skin graft group as compared with the primary closure group. All skin breakdowns
      appeared in the presence of a gibbus deformity, and gibbus deformity was more
      prevalent in the split-thickness skin graft group. The incidence of skin
      ulceration and gibbus deformity was site-dependent. A thoracic or thoracolumbar
      myelomeningocele repair with split-thickness skin graft was significantly more
      likely to be complicated by skin problems than the defect in the lumbar,
      lumbosacral, or sacral region. This relationship was secondary to the frequency
      of gibbus deformity in the more cephalad defects than defects caudad. A treatment
      plan is outlined that is based on the primary variable of the location of the
      myelomeningocele and secondarily by defect size.

PMID- 1984256
TI  - A multivariate approach to the treatment of peripheral nerve transection injury:
      the role of electromagnetic field therapy.
AB  - A multivariate approach to the treatment of peripheral nerve transection injury
      has been used in a rat model. A pilot study (48 animals, 8 groups) examined
      variables associated with the method and timing of surgical repair, the arrest of
      wallerian degeneration, and the role of pulsing electromagnetic field therapy
      (PEMF) in functional recovery. A second phase (90 animals, 6 groups) then studied
      the timing and duration of pulsing electromagnetic field therapy as the only
      variable in larger groups of animals. The pilot study revealed that a vein-graft
      conduit did not improve functional recovery compared with standard epineurial
      repair. Additionally, delayed repair compared favorably with immediate repair.
      The use of chlorpromazine to inhibit the toxic effects of calcium influx appeared
      to enhance early functional recovery, and the combination of delayed nerve repair
      and pulsing electromagnetic field therapy seemed to consistently improve
      function. The second phase of the study has demonstrated (for the first time)
      statistical improvement in ambulation in animals treated with delayed surgical
      repair and prolonged pulsing electromagnetic field therapy. We postulate that
      future treatment of nerve transection injuries will involve a combined treatment
      regimen consisting of the immediate arrest of wallerian degeneration, delayed
      surgery, and pulsing electromagnetic field therapy.

PMID- 1984257
TI  - Increase in skin-flap survival by the vasoactive drug buflomedil.
AB  - The effect of buflomedil to protect skin tissue from ischemia and necrosis was
      studied in random cutaneous flaps. Measurements were performed by intravital
      microscopy on the microcirculatory level of capillary perfusion in a flap model
      in the hairless mouse. In 30 hairless mice, single-pedicle flaps measuring 6 x 16
      mm were raised perpendicular to the spine of the animal. This flap develops a
      reliable amount of necrosis at its distal edge over a period of 7 days. A group
      of 10 mice received intravenous injections of buflomedil in doses of 3 mg/kg per
      day diluted in 0.1 ml normal saline beginning 4 hours before flap elevation and
      for 6 consecutive days postoperatively. In addition, 10 further animals received
      the same treatment except that it was started 5 minutes after flap elevation. In
      10 mice serving as controls, normal saline in equal volumes as in the
      experimental groups was applied. By means of intravital microscopy, functional
      vessel density (FVD) was determined in 2.5-mm increments from the flap's base to
      its distal edge at 1, 6, and 24 hours after elevation. Skin-flap survival was
      quantified by measuring the necrotic area on day 7 by means of digital
      planimetry. Functional vessel density was preserved in the distal flap of animals
      pretreated with buflomedil, revealing a higher functional vessel density at 10.0
      mm (p less than 0.01), 12.5 mm (p less than 0.05), and 15.0 mm (p less than
      0.001) from the flap's base as compared with controls.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1984258
TI  - The indestructible Bacillus bureaucraticus.

PMID- 1984260
TI  - Expanded preauricular full-thickness free skin graft.
AB  - A preauricular skin graft with expansion for repair of a facial defect is
      presented. This technique preserves a more natural appearance in color, texture,
      and thickness than is otherwise possible and provides a larger graft than the
      usual preauricular graft method.

PMID- 1984259
TI  - Lid margin reconstruction with an orbicularis oculi musculocutaneous advancement
      flap and a conchal cartilage graft.
AB  - A simple method to reconstruct the midlateral lid margin defect is described
      using an orbicularis oculi musculocutaneous advancement flap and a free conchal
      cartilage graft. This method is easy to perform not only in the lower eyelid, but
      also in the upper one, provides a natural gray line and a stable lid margin
      without postoperative eversion, and substitutes for the Leone and van Gemert
      procedure.

PMID- 1984261
TI  - A new method of methyl methacrylate fixation in skull reconstruction.
AB  - Fifty-two methyl methacrylate cranioplasties were performed in 47 patients over a
      5-year period. The indications for the original craniectomy fell into four
      categories. Nine patients had a craniectomy for tumor, 32 for trauma, 5 for
      infection, and 1 for aneurysm. A new approach, which eliminates the need for
      suture or wire fixation and which facilitates intraoperative calvarial
      contouring, is presented. An excellent cosmetic result is the norm with this
      technique.

PMID- 1984262
TI  - Craniofacial anomalies in twins.
AB  - Studies of twins provide insight into the relative contribution of genetic and
      environmental factors in the causality of structural anomalies. Thirty-five
      affected twin pairs were identified from a group of 1114 patients with congenital
      craniofacial deformities evaluated from 1972 to 1989. Forty-three of these 70
      twins exhibited one or more craniofacial anomalies; these were analyzed for
      dysmorphic characteristics, zygosity, concordance, and family history. The
      anomalies were categorized into two groups: malformations and deformations. The
      malformations (n = 36) included hemifacial microsomia (n = 10), cleft lip and
      palate (n = 8), cleft palate (n = 4), rare facial cleft (n = 2), craniosynostosis
      (n = 2), Binder syndrome (n = 2), Treacher Collins syndrome (n = 2), craniopagus
      (n = 2), CHARGE association (n = 1), frontonasal dysplasia (n = 2), and
      constricted ears (n = 1). The deformations (n = 7) included plagiocephaly (n =
      5), hemifacial hypoplasia (n = 1), and micrognathia (n = 1). Twenty-one
      monozygotic and 14 dizygotic twin pairs were identified. The concordance rate was
      33 percent for monozygotic twins and 7 percent for dizygotic twins.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1984263
TI  - Bilateral pinch reconstruction: versatility of the Masquelet-Zancolli flap and
      the Wilkki operation.

PMID- 1984264
TI  - A new dynamic lumbrical simulating splint for claw hand deformity.
AB  - The claw hand deformity, resulting from low ulnar or combined low ulnar and
      median nerve palsy, is an incapacitating situation. The splint described herein
      reverses the clawing by substituting for the lumbricals and interossei. If
      started early, it not only prevents the permanent stiffness of fingers in the
      claw position, but also effectively restores function without hampering day to
      day work because it is a surface splint.

PMID- 1984265
TI  - The history of maxillofacial prosthetics.

PMID- 1984266
TI  - The incidence of sarcomas of the breast among women in the United States, 1973
      1986.

PMID- 1984267
TI  - KAY aorta clamp for a bloodless field in lower lip surgery.

PMID- 1984268
TI  - The "safest" lower lid blepharoplasty.

PMID- 1984269
TI  - The hazard of multiple surgical specimens on a hypodermic needle.

PMID- 1984270
TI  - Corset platysmaplasty.

PMID- 1984271
TI  - What's missing from residency training?

PMID- 1984272
TI  - Capsular contracture: a new concept for an old problem.

PMID- 1984273
TI  - Fixation of sagittal fractures of the maxilla.

PMID- 1984274
TI  - Beauty is in the eye of the beholder.

PMID- 1984276
TI  - A portable and adjustable x-ray viewbox.

PMID- 1984275
TI  - Free muscle transplantation for treatment of facial paralysis: first experiences
      with the International Muscle Transplant Registry.

PMID- 1984277
TI  - Horizontal laxity of the lower lid.

PMID- 1984278
TI  - Hemifacial atrophy: value of radiographs.

PMID- 1984279
TI  - One-stage repair of blepharophimosis.
AB  - Congenital blepharophimosis is a congenital anomaly characterized by
      abnormalities in the area of the eyes, including bilateral ptosis, shortening of
      the horizontal fissure of the lid, expansion of the intercanthal distance, and
      epicanthus inversus. The condition is subject to autosomal-dominant heredity and
      is said to occur more frequently in Orientals than in Occidentals. Over the past
      9 years, we have surgically treated 11 cases of congenital blepharophimosis using
      a procedure in which levator resection and medial canthoplasty are performed in
      one stage. It has been commonly believed that when levator resection and medial
      canthoplasty are performed at the same time, tension in the eyelid becomes too
      strong to achieve favorable results; therefore, the standard procedure has been
      to divide the operation into two stages. In all 11 cases we experienced, however,
      it was possible to obtain good results with a single-stage operation.

PMID- 1984280
TI  - The resection of orbicularis oculi muscle from the upper eyelid in experimental
      surgery on the monkey.
AB  - The purpose of this study was to determine the maximum amount of orbicularis
      oculi muscle that may safely be resected from the upper eyelid without causing
      functional abnormalities. Measured amounts of that muscle were surgically excised
      from both upper eyelids in six cynomolgus monkeys. All the eyelids were
      photographed and videotaped at progressively increased intervals to permit the
      evaluation of wound healing, scarring, and function. Our preliminary results
      revealed that the excision of preseptal and partial supraorbital orbicularis
      oculi muscle, preseptal and complete supraorbital muscle, or pretarsal muscle
      only did not result in lagophthalmos. Complete resection of pretarsal, preseptal,
      and supraorbital orbicularis oculi did result in lagophthalmos but caused no
      corneal injury. The orbicularis oculi muscle in the cynomolgus monkey is similar
      to that in humans, but it is not yet clear whether our findings in the monkey are
      applicable in humans. A determination of the maximum amount of orbicularis oculi
      muscle that can safely be excised in humans would enable plastic surgeons to
      better understand and develop techniques for eyelid reconstruction and
      blepharoplasty.

PMID- 1984281
TI  - Evaluation of argon laser surgery in children under 13 years of age.
AB  - Argon laser surgery is an effective treatment for ectasias and congenital port
      wine stains; however, its use in children under the age of 13 is controversial.
      This paper reviews 202 children under the age of 13 who underwent argon laser
      treatments for congenital port-wine stains, spider angiomas, epidermal nevi, and
      lentigines. The clinical characteristics of port-wine stains in 170 children are
      discussed. Good to excellent results (moderate to complete clearing) in port-wine
      stains were obtained in 60 percent of patients and seemed to correlate best with
      lack of blanchability on pressure. Hypertrophic scarring was seen in only 7
      children, all of whom had undressed wounds; no significant scarring has been seen
      in any subsequent child who had maintained a dressed wound postoperatively.

PMID- 1984282
TI  - Augmentation rhinoplasty: observations on 1200 cases.
AB  - Over the past 14 years, from January of 1975 to December of 1988, we have done
      1263 aesthetic rhinoplasties using ear cartilage. In the field of augmentation
      rhinoplasty, many kinds of materials, such as bone, septal cartilage, ear
      cartilage, and prostheses, were used. In this paper, we limit discussion to our
      experience with the technique for the augmentation of the nasal dorsum using the
      ear cartilage and compare this with other materials. Patient ages ranged from 15
      to 72 years, with an average of 24 years. Some 95 percent of patients (1199) were
      female, and only 5 percent (64) were male. Patients were followed for a minimum
      of 6 months and a maximum of 20 months, with average follow-up only 8 months. Of
      course, we know that this is a very short follow-up period, but we could not
      follow patients longer because if they had no complaint about the results at the
      6-month visit, they never returned, despite our efforts. Five-hundred and ten of
      the 1263 patients (40 percent) had been augmented elsewhere, and the silicone
      prosthesis was already in place. However, 753 patients (60 percent) had no
      previous operation. For the 510 patients (secondary rhinoplasty patients), too
      high or too-large a prosthesis was the largest complaint in number, totaling 378
      cases (74 percent), and psychological dissatisfaction, such as pain or an
      uncomfortable sensation, was the second largest in number, totaling 104 cases (20
      percent). For the 753 patients (primary rhinoplasty patients), the main complaint
      was too-short or too-flat a nose (100 percent).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1984283
TI  - Skin retraction following suction lipectomy by treatment site: a study of 500
      procedures in 458 selected subjects.
AB  - I identified 500 suction lipectomy procedures involving sites on the body and in
      the cervicofacial region in 458 selected patients and studied the influence of
      treatment site on postoperative skin retraction by comparing preoperative and
      postoperative skin condition. Postoperative skin condition was evaluated first in
      the immediate postoperative period (second or third day); then at a more remote
      date (after at least 2 months of follow-up). On the body, restoration of the
      preoperative condition of the skin was obtained in 94.6 percent of treatment
      sites in the immediate postoperative period; after a longer follow-up, this
      proportion was 87.9 percent because of delayed development of modifications. The
      time interval needed to obtain a stable result increased with increasing age,
      regardless of the nature of this result, as well as with the total amount of fat
      removed. On the neck, liposuction improved or even eliminated preexisting skin
      looseness, and this improvement was even more noticeable as follow-up increased.
      The neck thus appears as the site of choice for suction lipectomy. On the face,
      in contrast, favorable results deteriorated over time, a finding that leads me to
      advocate combination with a face-lift whenever ptosis is present. Thus treatment
      site obviously has a substantial impact on the potential of the skin for
      retracting postoperatively.

PMID- 1984284
TI  - The surgical treatment of noma.
AB  - Noma is a gangrenous stomatitis affecting children from developing countries. It
      may leave dreadful mutilations around the mouth, with amputation of the lips,
      cheek, nose, lids, maxilla, palate, or mandibula. Reconstruction should take into
      account the size of the defect, the presence of trismus or constriction of the
      mandible, the age of the child, and the child's general condition. During the
      last 3 years, eight patients were treated at the Unit of Plastic and
      Reconstructive Surgery of the Hopital Cantonal Universitaire. Except in one case,
      tracheostomy was avoided, thanks to intranasal intubation by fibroscopy. These
      children, aged 2 to 9 years, underwent 31 general anesthesias and complex
      reconstructive procedures, including latissimus dorsi musculocutaneous
      pedunculated and free flaps, cranial flaps with galea, cranial bone and skin
      grafts, and retroauricular temporal skin flaps. All patients were able to return
      to Africa with dramatic functional and cosmetic improvements. However,
      satisfactory mouth opening and mandibular function were not always obtained.

PMID- 1984285
TI  - Cross-sectional physiology of the lung.
AB  - It is well known that gravity influences the physiology of the lung and thereby
      affects the intrapulmonary localization of disease processes. Less well known are
      the anatomic and physiologic differences in the axial or cross-sectional plane,
      which also affect the distribution of disease. Physiologic gradients in
      ventilation, perfusion, and lymph flow and stresses in the lung are present in
      the axial plane. Anatomic difference in branching patterns, interstitial design,
      and development of the secondary pulmonary lobules are also found. These regional
      disparities in anatomy and physiology can be applied to an old concept--the
      corticomedullary organization of the lung--and are used to consider why some
      diseases exhibit a propensity for the central or peripheral portions of the lung.
      The same analysis is applied to the anatomy and physiology in the secondary
      pulmonary lobule.

PMID- 1984286
TI  - Retained intrahepatic stones: treatment with piezoelectric lithotripsy combined
      with stone extraction.
AB  - Extracorporeal shock wave lithotripsy (ESWL) was performed in 11 patients with
      oriental cholangiohepatitis and intrahepatic stones associated with segmented
      strictures of intrahepatic ducts. All patients had previously undergone biliary
      surgery and basket extraction via a T-tube tract at the time of lithotripsy. The
      indication for ESWL was failure of, or anticipated difficulty with, basket
      extraction of the stones via a T-tube tract. A piezoelectric lithotriptor was
      used in all procedures. The average total number of shock waves administered was
      29,756 (range, 10,000-61,395). The average number of treatment sessions was 3.1
      (range, 1-6); the number of shock waves used in a single session ranged from
      10,000 to 15,000 with a frequency of five shots per second and 30%-50% power. In
      six patients, the stones were successfully fragmented and completely removed; in
      three of the others of the stones were fragmented and removed. The overall
      success rate, including complete (54%) and incomplete (27%) success, was 82%.
      Difficulty in targeting stones, and severe strictures and deformities of
      intrahepatic ducts, were the factors responsible for failure. No significant
      complications were observed.

PMID- 1984287
TI  - Alzheimer disease: measuring loss of cerebral gray matter with MR imaging.
AB  - The distributions of the cerebral gray matter, the white matter, and the
      intracranial cerebrospinal fluid (CSF) were measured in 14 patients with
      Alzheimer disease (AD) and in 14 healthy control subjects. The measurements,
      derived from two specifically designed magnetic resonance inversion-recovery
      sequences, compensate for partial signal averaging. The percentage of the gray
      matter in the brains of AD patients (44.9% +/- 4.4) was significantly lower than
      in control subjects (50.2% +/- 3.2). The most significant reduction (P less than
      .001) occurred in the temporal lobes (13.8%) and a central region (12.8); the
      reduction in frontal lobe (11.2%) and occipital lobe (9.2%) was also
      statistically significant (P less than .01). There was an increase in the CSF
      volume in the temporal, occipital, and frontal regions; no region showed a
      significant difference in the white matter content. The findings of diffuse
      changes and temporal lobe involvement in AD are consistent with pathologic
      observations of cortical cell loss.

PMID- 1984288
TI  - Patient care in interventional radiology: a perspective.

PMID- 1984289
TI  - Analysis of brain and cerebrospinal fluid volumes with MR imaging. Part I.
      Methods, reliability, and validation.
AB  - A computerized system was developed to process standard spin-echo magnetic
      resonance (MR) imaging data for estimation of brain parenchyma and cerebrospinal
      fluid (CSF) volumes. In phantom experiments, the estimated volumes corresponded
      closely to the true volumes (r = .998), with a mean error less than 1.0 cm3 (for
      phantom volumes ranging from 5 to 35 cm3), with excellent intra- and
      interobserver reliability. In a clinical validation study with actual brain
      images of 10 human subjects, the average coefficient of variation between
      observers for the measurement of absolute brain and CSF volumes was 1.2% and
      6.4%, respectively. The intraclass correlations for three expert operators is
      greater than .99 in the measurement of brain and ventricular volumes and greater
      than .94 for total CSF volume. Therefore, the authors believe that their
      technique to analyze MR images of the brain performed with acceptable levels of
      accuracy and reliability and that it can be used to measure brain and CSF volumes
      for clinical research. This technique could be helpful in the correlation of
      neuroanatomic measurements to behavioral and physiologic parameters in
      neuropsychiatric disorders.

PMID- 1984290
TI  - Analysis of brain and cerebrospinal fluid volumes with MR imaging: impact on PET
      data correction for atrophy. Part II. Aging and Alzheimer dementia.
AB  - A new, computerized segmentation technique, in which magnetic resonance (MR)
      imaging produces accurate volumetric measurements of brain and cerebrospinal
      fluid (CSF) without the limitations of computed tomography, was used in a
      retrospective analysis of digitized T2-weighted MR images of 16 healthy elderly
      control subjects and 16 patients with Alzheimer dementia. Ventricular and
      extraventricular CSF was quantified, and the effects of aging were studied; in
      both groups, the atrophy measurement was used to correct metabolic values
      obtained with positron emission tomography. Patients with Alzheimer dementia had
      higher total CSF; extraventricular, total ventricular, and third ventricular CSF
      volumes (49%, 37%, 99%, and 74%, respectively); and 7% lower brain volumes than
      the control group. The patients also showed a more marked decline in brain
      volumes and a greater increase in CSF volumes with advancing age than the control
      group. They had a 25.0% increase in corrected whole-brain metabolic rates; the
      control group had only a 15.8% increase. The use of this technique may provide a
      basis for further studies of aging and dementia, including regional volume
      analysis.

PMID- 1984291
TI  - Asymptomatic and neurologically symptomatic HIV-seropositive individuals:
      prospective evaluation with cranial MR imaging.
AB  - As part of a prospective multidisciplinary study of individuals seropositive for
      the human immunodeficiency virus (HIV), cranial magnetic resonance (MR) imaging
      was performed on 119 HIV-seropositive subjects (95 asymptomatic, 24 symptomatic)
      and the results were correlated with clinical data. MR images regarded as
      positive included those showing atrophy and/or white matter lesions. On the basis
      of these criteria, 96 subjects had normal MR images and 23 had abnormal images.
      Results of chi 2 analysis revealed a statistically significant difference between
      the asymptomatic group (12 of 95 [13%] with abnormal scans) and the symptomatic
      group (11 of 24 [46%] with abnormal scans) (P = .001). In the asymptomatic group,
      positive MR images showed fewer, smaller, and/or less extensive abnormalities.
      The researchers conclude that (a) MR imaging can show indirect evidence of HIV
      infection early in the disease, but abnormalities will be minor and seen only in
      a small minority of neurologically asymptomatic subjects; (b) the appearance of
      clinically recognizable neurologic disease correlates with the MR imaging
      findings of increasingly severe brain atrophy and white matter lesions; and (c)
      in some HIV-seropositive subjects, despite neurologic disease, MR images can
      remain normal. Results indicate that routine screening with cranial MR imaging of
      neurologically asymptomatic HIV-seropositive individuals would likely result in a
      low yield of positive findings.

PMID- 1984292
TI  - Three-dimensional reconstructed MR imaging of the inner ear.
AB  - The three-dimensional Fourier transform fast imaging with steady precession
      (FISP) technique was used to obtain high-resolution magnetic resonance (MR)
      images of the temporal bone region and to generate three-dimensional
      reconstructed images of the inner ear. The three-dimensional reconstructed images
      of the inner ear were directly synthesized from two-dimensional images of the
      temporal bone region by means of an external processing computer. With use of
      three-dimensional reconstructed images and stereoscopic observations, structures
      inside the temporal bone region and the positional relationship among them were
      easily recognized. These structures are difficult to demonstrate with two
      dimensional images. This three-dimensional method was also shown to be useful for
      recognition of disease and anatomic malformations in the temporal bone region.

PMID- 1984293
TI  - Sphenochoanal polyps: evaluation with CT and MR imaging.
AB  - A sphenochoanal polyp is a solitary mass of low attenuation on computed
      tomographic (CT) scans that arises from the sphenoid sinus and extends through
      the sphenoid ostium, across the sphenoethmoid recess, and into the choana (the
      boundary between the nasal cavity and nasopharynx). More often, however, a
      choanal polyp is an antrochoanal polyp, which arises from the maxillary antrum,
      protrudes through the middle meatus, extends into the nasal cavity, and continues
      back to the choana. Contiguous axial or coronal magnetic resonance and CT images
      help clearly differentiate the rare sphenochoanal polyp from the more common
      antrochoanal polyp. The sinus of origin is important to identify, as the surgical
      approach depends on the target sinus.

PMID- 1984294
TI  - Invasive lobular carcinoma: mammographic findings in a 10-year experience.
AB  - From January 1, 1976 to December 30, 1985, 1,966 cases of breast carcinoma were
      diagnosed and treated at Malmo General Hospital, Malmo, Sweden. Of these cases,
      185 (9.4%) involved invasive lobular carcinoma (ILC). Mammography in 137 cases
      demonstrated the following findings: spiculated opacity (53%), architectural
      distortion (16%), poorly defined opacity (7%), normal or benign findings (16%),
      and parenchymal asymmetry (4%). Radiographic definition of the ILC lesion varied
      greatly with projection: The craniocaudal view demonstrated significant findings
      more frequently than either the oblique or lateral views. Secondary radiographic
      findings were present in 31%, microcalcifications were rare, and physical
      findings were present in 89%. Because of its diffuse growth pattern and tendency
      to form lesions with opacity equal to or less than that of the parenchyma, ILC
      can be extremely difficult to detect mammographically. Therefore, the radiologist
      must be alert for subtle mammographic signs of malignancy and highly suspicious
      of any abnormal physical findings regardless of the mammographic appearance.

PMID- 1984295
TI  - Mammographic follow-up of low-suspicion lesions: compliance rate and diagnostic
      yield.
AB  - All recommendations for mammographic follow-up of low-suspicion lesions seen at
      mammography during a 6-month period were reviewed to establish compliance rate
      and eventual outcome. One hundred forty-four of 2,650 mammograms (5%) showed
      minimal abnormalities that warranted short-term and periodic mammographic follow
      up. Rates of compliance at 4 months and at 1, 2, and 3 years were 88%, 71%, 60%,
      and 47%, respectively. Progressive mammographic change was found in 10 patients,
      only one of whom had a carcinoma. It was concluded that mammographic follow-up of
      low-suspicion lesions is a reasonable alternative to surgical biopsy, although
      patient compliance remains a significant problem.

PMID- 1984297
TI  - Inferior hilar window.
AB  - The authors undertook a study to determine the ability to detect mass or
      adenopathy in the "inferior hilar window," a normally avascular region inferior
      to the shadow of the right pulmonary artery and vein and anterior to the
      descending left pulmonary artery on lateral chest radiographs. Fifty patients
      with normal results of thoracic computed tomography (CT) and 25 with unilateral
      or bilateral hilar masses or adenopathy (defined as opacity greater than 10 mm in
      diameter) were selected retrospectively. Patients with concomitant pulmonary
      masses or consolidation at CT that might be confused with or obscure an inferior
      hilar mass or adenopathy were excluded from study. The 75 corresponding lateral
      chest radiographs were then evaluated blindly. Forty-seven of the 50 normal cases
      were correctly interpreted (specificity = 94%). The anterior walls of the right
      and left lower lobe bronchi were seen in 36% and 84% of normal cases,
      respectively; the average thickness was 2 mm. Of the 25 patients with inferior
      hilar masses, 22 were recognized as having abnormalities (sensitivity = 88%); two
      of the three patients with false-negative results had right hilar masses. Overall
      accuracy was 92%. For only eight (32%) of the 25 patients was the laterality of
      abnormality correctly diagnosed. Evaluation of the inferior hilar window on
      lateral chest radiographs is accurate in assessing the presence or absence of
      inferior hilar mass or adenopathy.

PMID- 1984296
TI  - Immediate postoperative mammogram for failed surgical excision of breast lesions.
AB  - In a series of 200 consecutive preoperative needle localizations of non-palpable
      breast lesions, 128 lesions (64%) were calcified and 72 lesions (36%) were
      noncalcified on preoperative mammograms. Radiographs of the surgical specimen
      failed to confirm excision of 11 lesions (5.5%), seven calcified and four
      noncalcified. These 11 patients were taken directly from the surgical suite to
      the radiology suite, where an immediate postoperative mammogram was obtained. In
      five patients (2.5%), immediate postoperative mammograms showed surgical failure
      with the lesion still present. In six patients (3.0%), immediate postoperative
      mammograms showed that the lesion had been removed, even though the lesion had
      not been identified on surgical-specimen radiographs. No errors occurred in the
      interpretation of immediate postoperative mammograms, a fact corroborated by
      examination of surgical specimens obtained at repeat surgery in three patients
      and identification of skin calcifications in two patients, and with follow-up
      mammograms in six patients. Whenever a discrepancy between preoperative
      localization radiographs and surgical-specimen radiographs exists, the authors
      suggest immediate postoperative mammography to improve the diagnostic process.

PMID- 1984298
TI  - Mediastinal abnormalities: detection with storage phosphor digital radiography.
AB  - Conventional film radiography (FR) and six postprocessing algorithms of isodose
      storage phosphor digital radiography (SR) (0.2-mm X 10-bit pixel matrix) were
      compared in the evaluation of 40 mediastinal and 30 pulmonary lesions in 60
      patients who underwent computed tomography of the chest. The six SR algorithms
      varied among each other in only one image parameter. One algorithm approximated
      conventional image characteristics. The other five algorithms were designed to
      optimize imaging of the mediastinum and tested the effects of gray-scale
      reversal, adjustment of optical density, a linear instead of a sigmoid gradation
      curve, and moderate edge enhancement of high and medium spatial frequencies.
      Performance was evaluated by calculating the average area under the receiver
      operating characteristic curve (Az) of 5,040 observations by six readers. Post
      processing with high-frequency edge enhancement and density optimization for the
      mediastinum significantly improved performance of SR over FR in the detection of
      mediastinal lesions (Az = .80 +/- .02 vs .73 +/- .01, respectively). Gray-scale
      reversal significantly decreased performance (Az = .64 +/- .03). All SR
      algorithms that were postprocessed to optimize imaging of the mediastinum were
      significantly inferior to FR in the detection of pulmonary lesions.

PMID- 1984299
TI  - Data compression: effect on diagnostic accuracy in digital chest radiography.
AB  - High-resolution digital images make up very large data sets that are relatively
      slow to transmit and expensive to store. Data compression techniques are being
      developed to address this problem, but significant image deterioration can occur
      at high compression ratios. In this study, the authors evaluated a form of
      adaptive block cosine transform coding, a new compression technique that allows
      considerable compression of digital radiographs with minimal degradation of image
      quality. To determine the effect of data compression on diagnostic accuracy,
      observer tests were performed with 60 digitized chest radiographs (2,048 x 2,048
      matrix, 1,024 shades of gray) containing subtle examples of pneumothorax,
      interstitial infiltrate, nodules, and bone lesions. Radiographs with no
      compression, with 25:1 compression, and with 50:1 compression ratios were
      presented in randomized order to 12 radiologists. The results suggest that, with
      this compression scheme, compression ratios as high as 25:1 may be acceptable for
      primary diagnosis in chest radiology.

PMID- 1984300
TI  - Airway evaluation in children with use of ultrafast CT: pitfalls and
      recommendations.
AB  - Ultrafast computed tomographic (CT) evaluation of the airway can be performed
      with either 50-msec low-resolution images (cine CT) or 100-msec high-resolution
      images (high-resolution CT). To determine the best imaging strategy for ultrafast
      CT of the pediatric airway, the authors prospectively compared ultrafast CT and
      endoscopy in 20 children. Both studies were performed in 11 patients; cine CT
      alone was performed in six and high-resolution CT alone in three. Six patients
      had normal anatomy. Six patients had focal tracheal stenoses, four had
      tracheomalacia or laryngomalacia, one had a laryngoesophageal cleft, one had
      irregularity and narrowing in the subglottic area, one had laryngeal papillomas,
      and one had focal stenosis with stoma granuloma. Cine CT results agreed with
      those of endoscopy in 10 of 17 cases. In five cases focal stenosis was
      misinterpreted with cine CT as tracheomalacia. High-resolution CT results agreed
      with those of endoscopy in 10 of 14 cases. The results of a technique that
      combined high-resolution CT for the entire airway and cine CT at selected areas
      agreed with those of endoscopy in 10 of 11 cases; only a tracheoesophageal cleft
      was missed with the combined technique. For the greatest diagnostic accuracy with
      ultrafast CT in evaluation of the pediatric airway, both cine and high-resolution
      modes should be used.

PMID- 1984301
TI  - Blunt trauma in children: significance of peritoneal fluid.
AB  - Seven hundred ninety consecutively seen children who had not undergone peritoneal
      lavage underwent imaging with computed tomography (CT) after blunt trauma.
      Collections of peritoneal fluid were prospectively characterized as small (51
      children), moderate (32 children), or large (40 children). Associated injuries
      included hepatic or splenic injury in 74%, isolated renal or pancreatic injury in
      5%, isolated pelvic fracture in 5%, isolated hollow viscus injury in 5%, and a
      combination of the above in 7%. Peritoneal fluid was the only CT abnormality in
      three children. A significant correlation was found between presence and
      increasing size of peritoneal fluid collections and clinical signs of hemodynamic
      instability such as lower trauma score (P = .0008 by analysis of variance), the
      presence of arterial hypotension (P = .0001 by chi 2 test), and hematocrit less
      than 30% (0.30) (P = .0001 by chi 2 test). Additionally, the presence and amount
      of peritoneal fluid correlated with need for laparotomy and with mortality (P =
      .0001 by chi 2 test for both).

PMID- 1984302
TI  - Esophageal inflammation and stricture: complication of chronic granulomatous
      disease of childhood.
AB  - Esophagitis in children with immunodeficiency is most commonly due to
      opportunistic infection. The authors describe three patients with chronic
      granulomatous disease (CGD) of childhood who developed esophageal strictures that
      were believed to be complications of the primary disease. At radiologic
      examination, all three patients initially had a focal narrowing of the upper
      thoracic esophagus. Endoscopy showed no signs of opportunistic infection or
      Barrett esophagus. Biopsy of the strictures in two patients revealed findings
      consistent with CGD. In two of the three patients, inflammation extended to
      involve the middle and distal esophagus. Long-term response to balloon dilation
      was poor in the first two patients. The third patient was lost to follow-up after
      a partial clinical and radiographic response to dilation.

PMID- 1984303
TI  - Structural genitourinary defects detected in utero.
AB  - Fetal genitourinary anomalies are detected with increasing frequency due to the
      large numbers of fetuses that undergo screening ultrasonography (US) for
      nonspecific indications. One hundred seventy-seven patients were evaluated for
      fetal urinary abnormalities over a 2-year period. Fetal hydronephrosis accounted
      for 154 (87%) of the cases, with the remaining diagnoses including multicystic
      dysplastic kidney, autosomal recessive polycystic kidney disease, and renal
      agenesis or hypodysplasia. Ureteropelvic junction obstruction was the most common
      postnatal anatomic abnormality (29%), with a large number of cases of prenatally
      diagnosed hydronephrosis resolving either prenatally (33%) or postnatally (24%).
      Prenatal US findings were retrospectively analyzed with regard to the degree of
      hydronephrosis at different stages of gestation. Data showed that there is a
      gradual rise in anteroposterior renal pelvic diameter during gestation and that
      there is a correlation between this diameter and the ultimate renal outcome in
      regard to surgical repair. This information can provide guidance in making
      recommendations to parents and physicians.

PMID- 1984304
TI  - Nonpalpable cancer of the prostate: assessment with transrectal US.
AB  - Palpable cancer of the prostate is widely believed to be clinically significant.
      The authors compared the clinical significance of palpable prostate cancer with
      nonpalpable prostate cancer discovered with transrectal ultrasound (US). A strong
      association between lesion volume measured with preoperative transrectal US and
      volumetric measurements in 60 radical prostatectomy specimens permitted the use
      of tumor size measured with transrectal US as a reasonable estimation of gross
      tumor volume. In a subsequent clinical series, 147 biopsy-proved cancers were
      grouped according to size measured at US, the findings at digital rectal
      examination (DRE), and the Gleason score. For the 147 patients with known
      prostate cancer, a statistically significant difference between Gleason scores of
      palpable and nonpalpable cancers could not be demonstrated when the size of the
      tumor and its location within the prostate were held constant. Assuming that the
      Gleason score is a reliable indication of malignant potential and clinical
      significance, the authors conclude that nonpalpable prostatic cancer detected
      with transrectal US alone may be just as clinically significant as prostatic
      cancer discovered with DRE.

PMID- 1984305
TI  - Biologic aggressiveness of palpable and nonpalpable prostate cancer: assessment
      with endosonography.
AB  - The biologic aggressiveness of palpable versus nonpalpable prostate cancer was
      evaluated in 666 patients studied with endosonography over a 24-month period.
      Biologic aggressiveness was defined by a combined histologic and grade-stage
      category score. In 314 patients suspected of having prostate cancer 328 biopsies
      were performed. Carcinoma was detected in 99 patients, by means of both palpation
      and endosonography (n = 80), endosonography alone (n = 9), and palpation alone (n
      = 8); two cancers were not detected with either palpation or endosonography. All
      patients with normal results of digital examination had a combined grade-stage
      category score lower than 9. Fifty-five of 69 patients (80%) with abnormal
      results of digital examination and available histologic data had a histologic
      score of 6 or higher; 38 of these patients (69%) had a combined grade-stage
      category score of 9 or higher. Although the number of patients is small, these
      data suggest that nonpalpable cancers are biologically less aggressive than
      palpable ones and that the advantage of endosonography over palpation in
      detection of clinically significant cancers is limited.

PMID- 1984306
TI  - Congenital cystic disease of the seminal vesicle.
AB  - Thirteen cases of congenital seminal vesicle cysts with pathologic correlation
      were diagnosed between 1970 and 1988. Twelve of the 13 patients had ipsilateral
      renal anomalies. Intravenous urography, performed in 11 of the 13 patients,
      demonstrated associated renal anomalies. Computed tomography, performed in nine
      of the 13 patients, demonstrated associated renal anomalies and displayed the
      cystic seminal vesicles. Transabdominal or endorectal ultrasonography, performed
      in eight patients, allowed characterization of the seminal vesicle masses as
      cystic. Magnetic resonance imaging, performed in three of the 13 patients,
      accurately demonstrated dilated ejaculatory ducts into which ectopic ureters
      inserted. The fluid in the seminal vesicle cysts had an increased signal
      intensity on T1- and T2-weighted sequences. Seminal vesiculographic study
      demonstrated anomalous communications with the seminal tract. Cystic disease of
      the seminal vesicles can be either congenital or acquired; congenital cysts are
      associated with anomalies of the ipsilateral mesonephric duct.

PMID- 1984307
TI  - Detection of vascular complications in renal allografts with color Doppler flow
      imaging.
AB  - One hundred ninety-five color Doppler flow (CDF) examinations were performed in
      146 renal allografts to assess the capabilities of this technique in detecting
      intra- or extrarenal vascular complications. Conventional angiography was also
      performed in 44 transplants. In the group of transplants with angiographic
      correlation, CDF sonography enabled correct identification of 30 of 34 vascular
      complications. CDF showed 10 of 11 significant stenoses of the renal artery or of
      one of its main branches. There were two false-positive renal artery stenoses
      (one normal artery and one 40% stenosis). Nine of nine renal artery thromboses
      and the single pseudoaneurysm were also identified. Within the parenchyma, CDF
      sonography demonstrated five of five segmental infarcts, two of two postbiopsy
      arteriovenous fistulas, and three of six segmental or interlobar artery stenoses.
      Measurement of peak systolic velocity showed a significant difference (P less
      than .05) between a group (n = 8) with significant stenosis of the renal artery
      or one of its main branches (mean, 215.2 cm/sec +/- 32) and a group (n = 14)
      without stenosis (mean, 99.2 cm/sec +/- 19).

PMID- 1984308
TI  - Brain and cerebrospinal fluid volume: measurement with MR imaging.

PMID- 1984309
TI  - Translumbar arch aortography: a retrospective controlled study of usefulness,
      technique, and safety.
AB  - Subclavian and axillary artery stenoses may lead to axillofemoral bypass graft
      failure. These arteries were assessed preoperatively with arch aortography
      performed after conventional high translumbar peripheral aortography by
      exchanging the initial 16-gauge sheath for a 5-F pigtail catheter. Thirty-two
      diagnostic translumbar runoff and arch (TLR-arch) aortograms were obtained in 30
      patients with advanced lower extremity ischemia. In six patients (20%), the
      results of the arch study influenced the choice of an inflow site. These patients
      were compared with 70 control subjects who underwent conventional translumbar
      aortography without arch studies. In the TLR-arch group, two major complications
      occurred in one patient, while in the control group 11 major complications
      occurred in 10 patients. One retroperitoneal hematoma occurred in the TLR-arch
      group; two occurred in the control group. The mean change in hematocrit for the
      TLR-arch group was -3.81% (-0.0381), and for the control group it was -4.17% (
      0.0417). This difference was not statistically significant. Arch aortography is a
      valuable adjunct to the translumbar aortofemoral study. It can be simply
      performed without increasing the morbidity of the peripheral study.

PMID- 1984310
TI  - Valve and great vessel stenosis: assessment with MR jet velocity mapping.
AB  - For measurement of poststenotic jet velocities with magnetic resonance (MR)
      imaging, the authors reduced the echo time (TE) of the field even-echo rephasing
      (FEER) velocity mapping sequence from 14.0 to 3.6 msec, so minimizing the problem
      of MR signal loss from turbulent fluid. In vitro use of rotating disk and
      stenotic flow phantoms confirmed that the 3.6-msec TE sequence enables accurate
      measurement of jet velocities of up to 6.0 m/sec (r = .996). Peak jet velocity
      measurements were made with MR imaging in 36 patients with stenosis of native
      heart valves (n = 9), conduits (n = 19), or Fontan connections (n = 2) or with
      aortic coarctation (n = 6). Peak velocity measurements made with MR imaging
      agreed well with measurements made with Doppler ultrasound (US), which were
      available in 18 cases (standard deviation = 0.2 m/sec). Velocity mapping with
      fast-echo MR imaging is likely to have considerable importance as a noninvasive
      means of locating and evaluating stenoses, particularly at sites inaccessible to
      US, but care must be taken to prevent errors caused by malalignment, signal loss,
      phase wrap, or partial-volume effects.

PMID- 1984311
TI  - Insulinomas: localization with selective intraarterial injection of calcium.
AB  - To facilitate the noninvasive preoperative localization of islet cell tumors less
      than 15 mm in diameter, the authors examined the use of calcium as an insulin
      secretagogue in an arterial stimulation venous sampling (ASVS) technique. In four
      patients with episodic hypoglycemia, calcium gluconate (0.01-0.025 mEq Ca2+/kg)
      was injected directly into branches of the celiac plexus (gastroduodenal,
      splenic, and hepatic arteries) and the superior mesenteric artery. In all
      patients, serum levels of insulin rose abruptly in blood samples taken from the
      right hepatic vein 30 and 60 seconds after the infusion of calcium into the
      artery supplying the tumor; injection into an artery not supplying the tumor did
      not result in a similar rise. Accurate localization of the insulinomas was
      verified at surgery in three patients. In the fourth patient, who did not undergo
      surgery, arteriographic results were positive for insulinoma at the predicted
      site. On the basis of these results, the authors believe noninvasive ASVS may
      replace invasive portal venous sampling as the most effective method for the
      localization of occult insulinomas.

PMID- 1984312
TI  - Bleeding gastroesophageal varices: gastric vein embolization after partial portal
      decompression.
AB  - Shunts that decompress the portal vein are effective in the treatment of bleeding
      esophageal varices. Use of large-caliber portacaval shunts, however, results in
      the complete decompression of the portal system and the risk of subsequent
      development of hepatic encephalopathy. Use of small-caliber portacaval shunts
      results in mild portal hypertension and less frequent hepatic encephalopathy but
      may increase the risk of recurrent bleeding. Thirty-three patients underwent
      angiography after partial decompression portacaval shunting (median trans-shunt
      pressures, 8 mm Hg). Embolization of residual varices, noted in 13 patients, was
      performed. Results included one complication with no sequelae and no bleeding a
      mean of 13 months after the procedure was performed. Trans-shunt embolization of
      esophageal varices effectively prevents bleeding varices after partial portal
      decompression.

PMID- 1984313
TI  - The subtle and atypical mammographic features of invasive lobular carcinoma.

PMID- 1984314
TI  - Complications of percutaneous abdominal fine-needle biopsy. Review.
AB  - To determine whether the increasing use of percutaneous fine-needle biopsy of
      abdominal lesions is associated with an increase in serious complications, the
      author updated a literature search and evaluated a questionnaire (distributed
      among selected hospitals in the United States in 1986 and 1987) that followed up
      a questionnaire distributed in 1983. The updated literature review revealed a
      total of 24 deaths and 20 needle tract seedings. The updated questionnaire
      revealed five deaths after 16,381 biopsies (0.031%), whereas the previous
      questionnaire had shown four deaths after 63,108 biopsies (0.006%). Two similar
      European questionnaires revealed mortality rates of 0.008% and 0.018%,
      respectively. Of the total of 33 deaths, 21 involved biopsies of liver lesions;
      six involved pancreatic biopsies. Seventeen of the 21 deaths after liver biopsies
      were secondary to hemorrhage; five of the six deaths after pancreatic biopsies
      were due to pancreatitis. Of the 23 instances of needle tract seeding, 10
      occurred after biopsies of pancreatic malignancies. The frequencies of needle
      tract seeding in the four questionnaires were 0.005%, 0.006%, 0.003%, and 0.009%,
      respectively. Although infrequent, serious complications may be associated with
      this procedure. The author makes suggestions that may help minimize them.

PMID- 1984315
TI  - Improvement in CT pelvimetry.
AB  - When computed tomographic (CT) digital radiography is used for pelvimetry,
      measurement error may occur. Geometric distortion in the lateral direction of the
      CT digital radiograph can lead to an error in any measurement of the transverse
      pelvic inlet. The authors measured the magnitude of this error on two scanners
      and present a general method for correction of this potential error. The authors
      also showed that an additional dose reduction is possible if the patient is
      imaged in the posteroanterior rather than anteroposterior projection.

PMID- 1984316
TI  - Hemodialysis-related amyloidomas of bone.
AB  - Lytic bone lesions secondary to amyloid deposition are a recently described
      complication of long-term hemodialysis. The authors refer to these tumorlike
      deposits as amyloidomas in a review of the subject and four proved cases. This
      entity typically appears as multiple well-defined, juxta-articular lytic lesions
      without matrix calcification. The duration of hemodialysis is probably the
      greatest risk factor for development of these intraosseous amyloidomas.
      Ultrastructurally, this new type of amyloid originates from beta 2-microglobulin,
      a low-molecular-weight serum protein that is not filtered by standard dialysis
      membranes.

PMID- 1984317
TI  - The clinical efficacy of triple-injection wrist arthrography.
AB  - Triple-injection wrist arthrography has been demonstrated to increase the
      likelihood that all the ligamentous perforations in an injured wrist will be
      diagnosed. However, compared with imaging after single injection of contrast
      material into the radiocarpal joint, triple-injection arthrography not only
      increases patient expense but also significantly increases the time required of
      both patients and arthrographers to obtain the diagnosis. With the goal of
      decreasing the number of triple injections, the author reviewed 50 consecutive
      triple-injection wrist arthrograms. Using a technique based on high-volume
      injection of contrast material to achieve complete distention of the joint, the
      author achieved a false-negative rate for demonstration of complete perforations
      with radiocarpal injection alone of only 2% (10% if partial perforations were
      included). In none of these cases was patient treatment altered by the additional
      information provided by the second and third injections. This false-negative rate
      is significantly lower than that reported previously and raises the question of
      whether there are circumstances in which the easier and less time-consuming
      single radiocarpal injection might be appropriate.

PMID- 1984318
TI  - The role of radiologists in the American Heart Association: getting the message
      out.

PMID- 1984319
TI  - Occult posttraumatic osteochondral lesions of the knee: prevalence,
      classification, and short-term sequelae evaluated with MR imaging.
AB  - The prevalence, characterization, and classification of acute, post-traumatic,
      occult subcortical fractures of the knee, identified at magnetic resonance (MR)
      imaging, were evaluated prospectively in 120 consecutive patients first seen with
      acute posttraumatic hemarthrosis of the knee. Occult subcortical femoral and
      tibial fractures were identified in 72% of patients. A modified MR imaging
      classification is suggested based on a combination of the appearances of such
      lesions at MR imaging and their short-term osteochondral sequelae. Among 67% of a
      cohort of 21 patients first seen with what have been described as occult
      geographic subcortical fractures, osteochondral sequelae were seen at follow-up
      MR imaging 6-12 months later. The evidence from this study indicates that
      specific subcategories of occult subcortical knee fractures are associated with
      an inordinately high prevalence of osteochondral sequelae, especially significant
      cartilage damage.

PMID- 1984320
TI  - MR imaging of physiologic pituitary gland hypertrophy in adolescence.

PMID- 1984321
TI  - Endovaginal US: cardiac activity in embryos of less than 5.0 mm in crown-rump
      length.

PMID- 1984322
TI  - Medical audit of a rapid-throughput mammography screening practice.

PMID- 1984323
TI  - Extracorporeal shock wave lithotripsy of gallbladder stones: a pessimistic view.

PMID- 1984324
TI  - Gallstone lithotripsy: is there still cause for optimism?

PMID- 1984325
TI  - Oral cholecystography in contemporary gallstone imaging: a review.
AB  - The introduction of nonoperative alternatives to elective cholecystectomy in the
      management of gallstones has resurrected use of oral cholecystography (OCG). This
      article reviews basic principles involved in the proper performance of OCG and
      interpretation of the resulting images. The role of OCG in the current management
      of gallstones is discussed.

PMID- 1984326
TI  - Pharynx: value of oblique projections for radiographic examination.
AB  - The utility of oblique views for augmenting standard posteroanterior and lateral
      double-contrast radiography of the pharynx was examined. Over an 8-month period,
      two oblique views were added to the standard posteroanterior and lateral views of
      the pharynx during routine upper gastrointestinal studies in 102 patients divided
      into two groups. Group 1 consisted of 81 patients without suspected pharyngeal or
      esophageal disease who demonstrated what was considered to be normal anatomy on
      all radiographic views. Group 2 consisted of 21 patients who were known or
      suspected to have pathologic abnormality of the pharynx. The members of this
      latter group each demonstrated various abnormal pharyngeal anatomy on the
      standard views. In just over half of these cases the oblique projection
      contributed significant information not obtained with conventional views.
      Therefore, the authors conclude that oblique images are a beneficial addition to
      the diagnostic evaluation of patients highly suspected of having pharyngeal
      disease.

PMID- 1984327
TI  - Detection of gastric erosions: comparison of biphasic radiography with fiberoptic
      endoscopy.
AB  - Biphasic radiography was compared with fiberoptic endoscopy in detecting gastric
      erosions in a prospective, blinded study of 385 patients with dyspepsia. Because
      no absolute standard was available for the comparison, since histologic
      confirmation of all erosions was not possible, the kappa statistic was used to
      compare results from both modalities. Flat (incomplete) erosions were detected
      with endoscopy only and were considered to be present in 42 patients (11.2%).
      Varioliform (complete) erosions were identified with both radiography and
      endoscopy in 12 patients (3.2%). For the detection of varioliform erosions, a
      substantial agreement beyond chance between both modalities was found (kappa =
      0.73; standard error, 0.12). Thus, flat erosions were detected with endoscopy
      only, whereas state-of-the-art radiography and endoscopy were equally sensitive
      for detecting varioliform erosions. Histologic confirmation of erosions was
      obtained in only 75% of the patients. It is unknown whether the demonstration of
      erosions with radiography and/or endoscopy correlates with dyspepsia.

PMID- 1984328
TI  - Liver and pancreas: improved spin-echo T1 contrast by shorter echo time and fat
      suppression at 1.5 T.
AB  - T1-weighted spin-echo magnetic resonance (MR) images have had limited soft-tissue
      contrast at 1.5 T. The authors investigated the effects of echo-time (TE)
      minimization and fat suppression on MR images of the liver and pancreas. Two sets
      of MR images were obtained with identical repetition times and other parameters.
      In 10 subjects with seven liver lesions, images with TEs of 20 and 12 msec were
      compared. In 18 additional subjects with seven liver lesions and five pancreatic
      carcinomas, images with identical TEs but with and without fat suppression were
      compared. Contrast-to-noise ratios (CNRs) were greater with a TE of 12 msec than
      with a TE of 20 msec for liver versus spleen (7.6 vs 4.9, P = .014) and liver
      versus lesion (6.9 vs 3.9, P = .031). In patients without fatty liver, CNR for
      six lesions versus liver was greater (9.5 vs 6.0, P = .014) with fat suppression.
      CNR between glandular pancreas and cancer was most conspicuous with fat
      suppression, but fat planes were less distinct. Minimization of TE improves T1
      weighted images significantly. Fat suppression also improves CNR, but the
      disadvantages of fat suppression do not allow elimination of conventional T1
      weighted images.

PMID- 1984330
TI  - Sarcoidosis: abdominal manifestations at CT.
AB  - There are few data in the literature on the abdominal manifestations of
      sarcoidosis at computed tomography (CT). To determine whether differences in
      nodal distribution and appearance can be reliably used to distinguish between
      sarcoidosis and non-Hodgkin lymphoma (NHL), the authors retrospectively reviewed
      the abdominal and pelvic CT scans of 16 patients with biopsy-proved sarcoidosis
      and 20 patients with biopsy-proved NHL. Eleven of the 16 patients with
      sarcoidosis had abdominal and/or pelvic lymphadenopathy, which was common at all
      nodal sites except for the retrocrural and pelvic locations. There was a
      statistically significant lower frequency of retrocrual adenopathy in sarcoidosis
      than in NHL. Mean nodal size was significantly greater in NHL. Nodes tended to be
      confluent in NHL and discrete in sarcoidosis. Hepatomegaly was seen in six of the
      16 patients (38%) with sarcoidosis and splenomegaly was present in nine of 15
      (60%). CT depicted hepatic lesions in only three of eight patients (38%) with
      biopsy-proved hepatic involvement. Splenic lesions were seen at CT in five of the
      15 patients (33%). The authors believe that the overlap in nodal appearance and
      distribution poses a limitation for use of these criteria in accurate disease
      characterization.

PMID- 1984329
TI  - MR imaging of blood-borne liver metastases in mice: contrast enhancement with Fe
      EHPG.
AB  - To determine whether iron(III)ethylenebis-(2-hydrophenylglycine) (Fe-EHPG), a
      prototype hepatobiliary magnetic resonance imaging agent, can enhance the liver
      to-tumor contrast-to-noise ratio (C/N) in models of liver tumors in mice, two
      types of cell inoculation were used: intrahepatic implantation of M5076 sarcoma
      and intrasplenic injection of colon tumor (C-26) or M5076 sarcoma. Significant
      enhancement of the liver-to-tumor C/N and/or improved visualization of small
      lesions was consistently observed on T1-weighted images obtained after injection
      of the contrast material. For intrahepatic implants, the C/N on postinjection T1
      weighted images was superior to that on T1- and T2-weighted preinjection images.
      For the C-26 metastatic liver lesions of larger diameter (greater than 5 mm), the
      C/N on postinjection T1-weighted studies was superior to that on preinjection T1
      weighted images but was comparable to that on preinjection T2-weighted images.
      However, higher C/N after administration of Fe-EHPG improved visualization of
      medium-sized (3-5 mm) and small (1-3-mm) metastatic lesions in both M5076 and C
      26 models. These results demonstrate that MR imaging with appropriate
      hepatobiliary agents appears promising for early detection of liver metastases.

PMID- 1984331
TI  - Pancreatic cancer versus chronic pancreatitis: diagnosis with CA 19-9 assessment,
      US, CT, and CT-guided fine-needle biopsy.
AB  - The authors prospectively performed serum CA 19-9 assessment, ultrasound (US),
      computed tomography (CT), and CT-guided fine-needle aspiration biopsy (FNAB) of
      the pancreas in 81 consecutive patients with suspected chronic pancreatitis or
      pancreatic neoplasm. The final diagnosis was pancreatic cancer in 54 patients and
      chronic pancreatitis in 27 patients. CA 19-9 assessment, US, CT, and FNAB were
      considered nondiagnostic, respectively, in 0%, 25%, 19%, and 6% of cases. When a
      definite diagnosis was rendered, the positive predictive value was 90% for CA 19
      9 assessment, 95% for US, 98% for CT, and 100% for FNAB; the negative predictive
      value was, respectively, 69%, 95%, 86%, and 100%. The accuracy of all diagnostic
      and nondiagnostic studies was 81% for CA 19-9 assessment, 72% for US, 77% for CT,
      and 94% for FNAB. It is concluded that CT-guided pancreatic FNAB is the most
      reliable examination for enabling differential diagnosis of pancreatic cancer and
      chronic pancreatitis. When the pancreas is well visualized at US, the negative
      predictive value for pancreatic cancer is more accurate than that of CA 19-9
      assessment and CT.

PMID- 1984332
TI  - Body composition in myelomeningocele.
AB  - Body composition and measures of obesity were evaluated in 59 subjects with
      myelomeningocele (MMC), aged 0.3-29 y, by anthropometry and measures of body cell
      mass (BCM) and intra- and extracellular water (ICW and ECW), derived from total
      body potassium and deuterium-isotope dilution; these results were compared with
      reference data. Body composition was normal in preambulatory children with MMC.
      Beyond ages 3-4 y there was significant depletion of BCM and total body water,
      with maldistribution of water (increased ECW and decreased ICW) and increased
      percentage body fat above that expected for age and sex. These findings were more
      pronounced in females and in those with high lesions, and were less pronounced in
      those who remained ambulatory. These changes may result in metabolic and
      nutritional maladaption during stress. The relation of BCM, total body water
      depletion and increased ECW to decreasing ambulatory activity suggests that early
      nutritional and mobility programs warrant further study.

PMID- 1984333
TI  - Effect of chronic alcohol administration on transketolase in the brain and the
      liver of rats.
AB  - To estimate the nutritional and the pathological states in thiamin-deficiency
      related diseases, especially Wernicke-Korsakoff syndrome, we studied the
      relationship among transketolase activity, transketolase concentration, and
      thiamin phosphate esters in rats chronically fed alcohol. In the brain of alcohol
      fed rats, the enzyme activity and concentration decreased although there was no
      positive correlation between the two. On the contrary, transketolase activity in
      the liver correlated positively with concentration, and both transketolase
      activity and concentration were decreased in the thiamin-deficient groups. These
      findings suggest that transketolase in the brain may be different from that in
      the liver and that the alteration of the enzyme activity in the brain may be
      based on the conformational change of the protein molecule caused by chronic
      alcohol administration.

PMID- 1984334
TI  - Calcium supplementation: effect on iron absorption.
AB  - The influence of calcium supplements on the absorption of dietary nonheme iron
      and of iron supplements was evaluated in 61 normal volunteer subjects by use of a
      double-radioisotope technique. When taken without food, calcium carbonate did not
      inhibit the absorption of ferrous sulphate with doses of either 300 mg Ca and 37
      mg Fe or 600 mg Ca and 18 mg Fe. However, at the latter levels, calcium citrate
      and calcium phosphate reduced iron absorption significantly by 49% and 62%,
      respectively. All calcium supplements inhibited absorption of the iron supplement
      when taken with food. The absorption of dietary nonheme iron was also inhibited
      by all three supplements. This inhibition was less pronounced from a meal of high
      iron availability and low calcium content (28%) than from a breakfast meal of low
      iron availability and high calcium content (55%). These results suggest that
      taking regular calcium supplements with meals makes it more difficult for women
      to meet their daily iron requirement.

PMID- 1984335
TI  - Calcium: effect of different amounts on nonheme- and heme-iron absorption in
      humans.
AB  - We investigated the effect of calcium on iron absorption in 126 human subjects.
      Addition of calcium chloride to wheat rolls significantly reduced iron
      absorption. Doses between 40 and 600 mg Ca were studied. The inhibition was
      clearly dose related up to 300 mg Ca. Calcium added to the dough when making the
      rolls reduced phytate degradation during fermentation and baking. As little as 40
      mg Ca added to 80 g flour reduced phytate degradation by 50%, thus increasing the
      phytate content of the rolls to levels interfering with iron absorption. Calcium
      also had a direct dose-related inhibiting effect on iron absorption, noted by
      adding calcium to the rolls after they had been baked instead of to the dough.
      Iron absorption was reduced by 50-60% at doses of 300-600 mg Ca. Giving 165 mg Ca
      as milk, cheese, or calcium chloride reduced absorption by 50-60%. The same
      amount of calcium also significantly reduced heme-iron absorption, suggesting
      that the effect of calcium is related to the mucosal transfer of iron. The
      observed marked inhibitory effect on iron absorption of calcium in amounts
      frequently encountered in normal meals has important nutritional implications.

PMID- 1984336
TI  - Selenium metabolism and platelet glutathione peroxidase activity in healthy
      Finnish men: effects of selenium yeast, selenite, and selenate.
AB  - The mean dietary selenium intake in Finland increased from 40 to 100 micrograms/d
      in 1987 because of the addition in 1985 of selenium to fertilizers. A selenium
      supplementation study was performed in 1987 on the same men as were followed in a
      1981 study that had a similar design (200 micrograms Se/d). Selenite and
      selenate, but not selenium yeast increased platelet glutathione peroxidase
      (GSHPx) activity by 30% compared with placebo, much less than the 70% found in
      the previous study. Selenium yeast and selenite increased plasma selenium after
      11 wk from 1.39 mumol/L to peak values of 2.15 and 1.58 mumol/L, respectively.
      Only yeast selenium was incorporated into red cells. From a regression plot based
      on present and literature data, it was estimated that the plasma selenium
      concentration needed to achieve maximal platelet GSHPx activity was 1.25-1.45
      mumol/L. At the present selenium intake in Finland, 100 micrograms/d, GSHPx
      activity is saturated in plasma and red cells and almost saturated in platelets.

PMID- 1984337
TI  - Biochemical indices of selected trace minerals in men: effect of stress.
AB  - Plasma zinc, iron, copper, and selenium and selected blood proteins were measured
      in 66 men before (BHW) and after (AHW) a 5-d period of sustained physical and
      psychological stress called Hell Week. Recovery blood samples were obtained from
      26 men 7 d after Hell Week. Dietary intakes were determined BHW and during Hell
      Week; zinc, iron, copper, and selenium intakes during Hell Week averaged 23.6 +/-
      3.4 mg/d, 35.4 +/- 3.9 mg/d, 3.0 +/- 0.5 mg/d, and 92.5 +/- 26.7 micrograms/d,
      respectively. C-reactive protein was detected in only five subjects BHW and in
      all subjects AHW. Zinc, iron, selenium, and albumin decreased by 33%, 44%, 12%,
      and 9%, respectively, whereas ferritin, ceruloplasmin, and creatine kinase
      concentrations increased AHW by 59%, 8%, and 266%, respectively. Haptoglobin
      concentrations increased 57% in 30 subjects but decreased 32% in 23 subjects AHW.
      The biochemical changes were transitory because protein (except ferritin) and
      mineral concentrations were similar to BHW values 7 d after Hell Week. Hell Week
      induced changes characteristic of an acute-phase response in physically active
      men.

PMID- 1984338
TI  - Bone density in premenopausal women: effects of age, dietary intake, physical
      activity, smoking, and birth-control pills.
AB  - The effects of age, calcium, smoking, and physical activity on appendicular and
      axial bone mineral density (BMD) were evaluated in a 2-y study of 200-300 healthy
      young women aged 20-39 y. There was no cross-sectional change of BMD with age or
      longitudinal change with bone loss. No effect of birth-control pills on BMD was
      seen. There also was no association of calcium intake with BMD and/or with BMD
      changes. Current calcium intake was not a significant influence on BMD in this
      age group. Daily activity had no effect on BMD and there was no apparent additive
      interaction of activity and calcium intake on BMD. Smokers had significantly
      lower spine BMD and a tendency for lower BMD at other sites. Body weight was a
      better predictor of BMD than was any other factor. There was no association of
      BMD or BMD changes with both urinary calcium and hydroxyproline normalized for
      creatinine.

PMID- 1984339
TI  - Seasonal changes in 24-h and basal energy expenditures in rural Gambian men as
      measured in a respiration chamber.
AB  - Adaptation of 24-h energy expenditure (24-h EE) to seasonal variations in food
      availability was studied, by using a respiration chamber, in 18 rural Gambian men
      on three occasions: period 1--at the end of the rainy season, which is
      characterized by low food availability; period 2--during the nutritionally
      favorable dry season; and period 3--at the onset of the following rainy season.
      From periods 1 to 2 body weight increased by 2.8 +/- 0.4 kg, and a rise in 24-h
      EE was observed (from 8556 +/- 212 kJ/d to 9166 +/- 224 kJ/d), which was
      correlated to weight change (r = 0.73, P less than 0.001). During period 3, 24-h
      EE averaged 8740 +/- 194 kJ/d. Diet-induced thermogenesis increased significantly
      from periods 1 to 2 (5.9 +/- 0.5% to 8.2 +/- 0.8%) and subsequently decreased to
      3.6 +/- 0.6% during period 3. In rural Gambian men, metabolic adaptations in
      response to seasonal changes in food availability are reflected by a decrease in
      body weight, mainly manifested by a loss of fat-free mass accompanied by a
      decreased 24-h EE and a lowered diet-induced thermogenesis.

PMID- 1984340
TI  - Lipid infusion increases oxygen consumption similarly in septic and nonseptic
      patients.
AB  - This investigation compared the metabolic effects of lipid infusion in five
      septic and five nonseptic patients. Oxygen consumption was determined by indirect
      calorimetry over 1 h of rest and during 2 h when Intralipid (20%) was infused
      [166 mL/h; 23 kJ/min (5.5 kcal/min)]. Septic patients had a resting metabolic
      rate 17% higher than that of their nonseptic control subjects and a significant
      (P less than 0.05) rise (13%) in oxygen uptake was measured in both groups of
      subjects during the 2-h infusion of lipid. Preinfusion respiratory quotient (RQ)
      was 7% higher in the septic patients (P less than 0.05), and during the infusion
      period RQ decreased similarly (approximately 6%; P less than 0.05) in both
      groups. Plasma catecholamines were elevated in the septic patients preinfusion
      and the concentrations remained unaltered during the infusion. Norepinephrine
      rose significantly in the nonseptic group with the lipid infusion. The results
      show that sepsis has little or no influence on the characteristic rise in
      metabolic rate that occurs with intravenous lipid.

PMID- 1984341
TI  - Influence of breakfasts with different nutrient contents on glucose, C peptide,
      insulin, glucagon, triglycerides, and GIP in non-insulin-dependent diabetics.
AB  - To examine the influence of coingestion of fat and protein in a mixed meal on
      carbohydrate metabolism, subjects with non-insulin-dependent diabetes mellitus
      (NIDDM) received three different breakfasts varying in the amount of fat and
      protein (group 1) or only in the amount of fat (group 2). Compared with the
      changes after a standard breakfast, insulin increased after the protein-rich meal
      and decreased after the fat-rich meal in group 1. Glucose and gastric inhibitory
      polypeptide (GIP) remained constant. In contrast, only GIP showed a significant
      increase after a high-fat meal in group 2. Thus, in NIDDM subjects, glucose and
      insulin responses to different mixed meals do not appear to be exclusively
      mediated by GIP. Protein was confirmed as a potent stimulator of insulin
      secretion. Other factors, such as an altered beta-cell response in diabetics to
      GIP or other incretions, must be considered to explain the reported results.

PMID- 1984342
TI  - Resting and total energy expenditure in patients with inflammatory bowel disease.
AB  - Patients with inflammatory bowel disease often present with weight loss. Among
      possible causes, an elevated energy expenditure has frequently been suggested but
      is the least documented. In this study resting metabolic rate (RMR) and total
      daily energy expenditure (TDEE) were measured in 15 outpatients with inflammatory
      bowel diseases and in eight healthy control subjects. Measured RMR as a
      percentage of that predicted from fat-free mass was not significantly different
      for control subjects (102 +/- 9.8%, mean +/- SD) and patients (100 +/- 13.3%).
      TDEE, expressed as a multiple of RMR, was 1.70 +/- 0.31 for control subjects and
      1.78 +/- 0.24 for patients. When patients were subgrouped as greater than or
      equal to 90% or less than 90% desirable body weight, a mean increase over RMR
      predicted from fat-free mass was seen in the underweight patients (106 +/- 9.3%)
      but not in normal-weight patients (99.0 +/- 15.6%). Mean TDEE/RMR values for the
      patient subgroups were 1.70 +/- 0.30 and 1.88 +/- 0.08, respectively. We conclude
      that stable outpatients with inflammatory bowel disease have only a minimal
      increase in energy needs.

PMID- 1984343
TI  - Protein metabolism in obesity: effects of body fat distribution and
      hyperinsulinemia on leucine turnover.
AB  - To examine whether moderate obesity and differences in body fat distribution are
      associated with abnormalities of protein metabolism, leucine turnover was
      measured in three groups of age-matched premenopausal women. Ten upper-body-obese
      (UB Ob), 10 lower-body-obese (LB Ob), and 10 nonobese (Non Ob) women were studied
      in an overnight postabsorptive condition (basal) and again during an infusion of
      low physiologic amounts of insulin (insulin clamp). Results showed that basal
      leucine carbon flux was greater (P less than 0.05) in UB Ob and LB Ob women than
      in Non Ob women (2.96 +/- 0.08 vs 3.14 +/- 0.16 vs 2.68 +/- 0.08 mumol.kg lean
      body mass-1.min-1, respectively; mean +/- SEM). Leucine carbon flux was not
      suppressed during the insulin-clamp study in UB Ob women but was in the LB Ob and
      Non Ob women. We conclude that moderate obesity is associated with increased
      proteolysis and that insulin's antiproteolytic actions are impaired in upper-body
      obesity. These findings could have implications for future studies of and
      treatment of obesity.

PMID- 1984344
TI  - Health implications of the n-3 fatty acids.

PMID- 1984345
TI  - Do bioimpedance changes reflect weight, not composition?

PMID- 1984346
TI  - Is the bioelectrical-impedance method valid?

PMID- 1984347
TI  - Reappraisal of the resting metabolic rate of normal young men.
AB  - The Harris-Benedict (HB) equation, widely used to estimate the resting metabolic
      rate (RMR), has been disputed by Owen et al who reported that it overestimates
      the RMR of men aged less than 50 y by approximately 9%. We measured the RMR of 29
      healthy, nonsmoking men aged 18-33 y by direct oxygen consumption with a closed
      circuit technique similar to that used by Harris and Benedict (respirometer), as
      well as by a ventilated-hood technique. RMR determined by the ventilated-hood
      technique was 5.6% lower than when determined by the respirometer (1643 +/- 148
      vs 1721 +/- 145 kcal/d, respectively, means +/- SD; P less than 0.001). RMRs by
      both these methods were lower than the value of 1813 +/- 164 kcal/d predicted by
      the HB equation; the 95% confidence intervals (CIs) for RMR were 92.4-98.1%
      (respirometer) and 88.5-91.1% (ventilated hood) of the value predicted by the HB
      equation. The 95% CI for RMR determined by ventilated hood was 98.4-103.5% of the
      value predicted by using a new equation proposed by Owen et al. We conclude that
      the HB equation overestimates RMR by 9.2% in normal young men. This could be due
      in part to the inherent discomfort experienced by subjects when the original
      technique was used.

PMID- 1984348
TI  - The effect of exercise on food intake in men and women.
AB  - To study the effect of acute exercise on caloric intake in normal-weight young
      people, food intake was monitored in 10 men and 10 women during consecutive 5-d
      periods, one with and one without exercise. Food intake during the exercise
      period was compared with that during the control period. Caloric intake during
      the control period was 2467 +/- 165 kcal/d (means +/- SEM) for men and 1831 +/-
      103 kcal/d for women. During the exercise period the men increased their caloric
      intake to 2658 +/- 188 kcal/d and the women's caloric intake remained unchanged,
      1830 +/- 91 kcal/d. Caloric intake was not affected by sequence of treatment or
      duration of protocol. Men responded to 5 d of acute exercise with increased
      caloric intake (208 +/- 64 kcal/d), which was insufficient to compensate for the
      caloric cost of exercise (596 kcal/d above resting metabolic rate). Women did not
      change their caloric intake despite expending 382 kcals/d during exercise.
      Consequently, both normal-weight men and women were in negative caloric balance
      during the exercise period.

PMID- 1984349
TI  - Lysozyme, lactoferrin, and secretory immunoglobulin A content in breast milk:
      influence of duration of lactation, nutrition status, prolactin status, and
      parity of mother.
AB  - Milk lactoferrin (LF), lysozyme (LZ), and secretory IgA (sIgA) were measured
      cross-sectionally in 127 Zairean mothers, lactating greater than or equal to 18
      mo. The 54 urban mothers were of marginal nutrition status [body mass index (BMI)
      22.6 +/- 2.6 kg/m2 and albumin 33.1 +/- 4.5 g/L]. The neighboring rural mothers
      were of significantly (P less than 0.001) poorer nutrition status (BMI 20.5 +/-
      2.2 kg/m2 and albumin 27.7 +/- 5.4 g/L). In both urban and rural mothers, as
      lactation progressed LF decreased by 33% and 55% whereas sIgA remained unchanged
      and LZ steadily increased. There was more LZ and sIgA in rural milk, contrasting
      with the poorer maternal nutrition. As calculated from individual milk yields,
      the urban infants were fed daily with twice as much LF and sIgA but with similar
      amounts of LZ as were the rural infants. In the early stage of lactation, the
      milk of both groups of Zairean mothers contains more sIgA than that of a group of
      west European (Belgian) mothers (n = 20), but the LF and LZ contents were rather
      similar.

PMID- 1984350
TI  - Percent body fat in obese white females predicted by anthropometric measurements.
AB  - The percent body fat (PBF) and 15 anthropometric measurements were measured in
      221 obese white females randomly assigned to validation and cross-validation
      groups. Two new anthropometric equations for the prediction of the percent of
      body fat were generated by multiple regression. Equation 1 includes the residual
      lung volume (RV) as a factor and had a correlation coefficient (r) of 0.85 and a
      standard error of the estimate (SEE) of 3.9%. Equation 2 does not include the RV
      and has an r of 0.82 and an SEE of 4.3%. Both equations were more precise than
      two previous widely used equations. In a subgroup of 37 subjects who underwent
      weight loss, equation 1 gave a more precise estimate of the change in PBF. We
      conclude that the new equations permit a better prediction of the PBF in obese
      white females.

PMID- 1984351
TI  - Plasma pyridoxal and pyridoxal 5'-phosphate concentrations in response to
      ingestion of water or glucose polymer during a 2-h run.
AB  - The effects of ingesting a glucose polymer solution (GP) or water (W) on plasma
      pyridoxal 5'-phosphate (PLP) and pyridoxal (PL) concentrations were compared in
      six men (age: 30 +/- 2 y; VO2max: 57.4 +/- 3.2 mL.kg-1.min-1) under running (R)
      and control (C) conditions. Subjects ran for 2 h at 60-65% of VO2max for R and
      remained standing for C. For both R and C, 200 mL W or GP was ingested before (0
      time) and every 30 min while running (30, 60, and 90 min). Plasma PLP decreased
      to 95% and 87% of 0-time at 180 min for WC and GPC and increased to 126% and 119%
      at 90 min and to 124% and 119% at 120 min for WR and GPR. By 60 min postrun,
      plasma PLP was 98% (WR) and 101% (GPR) of 0-time. There were no significant
      differences between W and GP conditions. Changes in PLP were not related to
      plasma volume or blood glucose, free fatty acids, lactate, alkaline phosphatase,
      aspartate aminotransferase, or alanine aminotransferase. No significant changes
      in plasma PL were noted. Exercise induces an increase in plasma PLP, perhaps due
      to transfer of B-6 vitamers from liver to skeletal muscle.

PMID- 1984353
TI  - Thank heavens for crazy people.

PMID- 1984354
TI  - Ways to nurture your creativity.

PMID- 1984352
TI  - Vitamin E (tocopherols) in human cerebrospinal fluid.
AB  - Cerebrospinal fluid (CSF) and blood were obtained at the time of myelographic
      examinations from 40 adult, male, human subjects with no neurologic or metabolic
      abnormalities. Vitamin E (tocopherols) concentrations were determined by liquid
      chromatography. In subjects with normal concentrations of CSF protein (n = 22),
      the alpha- and gamma-tocopherol concentrations were 29.2 +/- 9.5 (mean +/- SD)
      and 6.5 +/- 3.6 nmol/L, respectively, in CSF and 26.0 +/- 8.1 and 6.0 +/- 3.6
      mumol/L, respectively, in serum. The concentrations of alpha-tocopherol in CSF
      correlated significantly (P less than 0.001) with both total protein and albumin
      concentrations, suggesting that tocopherol transport into CSF is linked with that
      of plasma proteins. In vitro oxidation of vitamin E in CSF by the free-radical
      generator 2,2'-azobis-(2-amidinopropane) hydrochloride showed a measurable
      induction (lag) period. This is due to the presence of other antioxidants in
      human CSF.

PMID- 1984355
TI  - Questioning the use of invasive technology.

PMID- 1984356
TI  - MDs bill for these routine nursing tasks.

PMID- 1984358
TI  - New support for the failing heart.

PMID- 1984357
TI  - Restoring urinary continence.

PMID- 1984360
TI  - Books of the year.

PMID- 1984359
TI  - From jump ropes to stethoscopes.

PMID- 1984361
TI  - Northeast jobfocus. How case management is changing the picture.

PMID- 1984362
TI  - Not-such-cockeyed optimists.

PMID- 1984363
TI  - Speaking of sex.

PMID- 1984364
TI  - Don't tie that T tube.

PMID- 1984365
TI  - Amino acids fail to prevent halothane depression of albumin synthesis: studies in
      the isolated perfused rat liver.
AB  - Halothane (1.3 MAC) and ethanol (0.4%) depress albumin synthesis in isolated
      perfused rat livers (IPRLs). Addition of amino acids prevents depression by
      ethanol. We have examined the effects of amino acids on albumin synthesis by
      IPRLs exposed to halothane. Seventeen livers were perfused with a mixture of rat
      erythrocytes and rabbit plasma. Five were exposed to oxygen/carbon dioxide alone
      and 12 to oxygen/carbon dioxide with 1.5% halothane. A mixture of 10 essential
      amino acids was added to the perfusate of six of the halothane-exposed livers to
      a concentration approximately 10 times the normal rat plasma level. Perfusate
      concentrations of newly synthesized albumin were measured by radial
      immunodiffusion, and the rate of synthesis for the 4.25-h study period was
      calculated. The mean +/- SEM albumin synthetic rate (mg/h per 300-g rat) in the
      control group (12.13 +/- 1.36) was significantly greater than in the group
      receiving halothane alone (6.98 +/- 0.92). Amino acid treatment failed to prevent
      halothane depression of albumin synthesis (8.68 +/- 0.84). Thus, although amino
      acids block ethanol depression of albumin synthesis, we could show no such effect
      in rat livers exposed to halothane.

PMID- 1984366
TI  - Interpleural analgesia after thoracotomy.
AB  - We examined the effects of the following variables on interpleural analgesia
      after thoracotomy: addition of epinephrine to local anesthetic, thoracostomy
      drainage, two-catheter placement, and location of catheter tips. Twenty patients
      were randomized to have one catheter (paravertebral tip location) or two
      catheters (paravertebral and lateral thoracic wall tip locations). Interpleural
      catheters were sutured to the parietal pleura by the surgeon at time of wound
      closure. Patients were then randomly assigned to receive 20 mL of 0.5%
      bupivacaine with 1:200,000 epinephrine through the single catheter or 10 mL of
      0.5% bupivacaine with or without 1:200,000 epinephrine through each of the two
      catheters while supine. Bupivacaine concentrations in whole blood and in
      thoracostomy drainage fluid were assayed by gas chromatography. Actual content of
      bupivacaine in the drainage fluid was calculated. Degree of analgesia was
      assessed by verbal numerical pain scores over the first 4 h and opioid demand
      thereafter. Addition of epinephrine to bupivacaine did not influence the degree
      of analgesia. Approximately 30%-40% of any administered dose of bupivacaine was
      lost via the thoracostomy tube over a 4-h period. There was no correlation
      between the true initial dose (100 mg minus thoracostomy drainage) and Cmax. Use
      of two catheters resulted in significantly less opioid requirements after an
      initial 8-h period. Failure to achieve adequate interpleural analgesia in
      postthoracotomy patients may be related to loss of anesthetic via thoracostomy
      drainage, presence of extravasated blood and tissue fluid in the pleural space,
      and possibly sequestration and channeling of flow of local anesthetic by
      restricted motion of an operated lung.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1984367
TI  - Effects of hydralazine and prostaglandin E1 on regional myocardial function in
      the ischemic canine heart.
AB  - The effects of hydralazine and prostaglandin E1 on regional myocardial function
      were studied in dogs. Sixteen dogs were randomly assigned to one of two drug
      treatment groups of eight dogs each. The first group (G1) was treated with 0.4
      mg/kg hydralazine administered as a bolus. The second group (G2) received
      prostaglandin E1 given as an infusion for a total dose of 0.8 micrograms/kg.
      Regional myocardial function was assessed through the measurement of myocardial
      segment shortening during systole. We call this index percent systolic shortening
      (%SS). An ischemic heart preparation was created by partial occlusion of coronary
      blood flow. The degree of induced ischemia was determined by following the
      reduction in %SS. Hydralazine reduced %SS of the ischemic myocardium while
      increasing the cardiac index, stroke volume index, and coronary blood flow.
      Prostaglandin E1 increased %SS, cardiac index, and stroke volume index in the
      ischemic heart preparation. Hydralazine, therefore, induced dissociation between
      global ventricular function and regional myocardial function whereas
      prostaglandin E1 did not. The present findings emphasize that evaluation of
      vasoactive drugs should consider their effects on regional myocardial function as
      well as on global hemodynamics.

PMID- 1984368
TI  - Caudal morphine for postoperative analgesia in infants and children: a report of
      138 cases.

PMID- 1984369
TI  - Correct application of the shunt fraction calculation.

PMID- 1984370
TI  - ECG signals during cardiopulmonary bypass: artifacts or reality?

PMID- 1984371
TI  - Epidural blood patch: why the rapid response?

PMID- 1984372
TI  - A modest proposal for improved humidifier design.

PMID- 1984373
TI  - Cardiodynamic effects of propofol in comparison with thiopental: assessment with
      a transesophageal echocardiographic approach.
AB  - In 40 patients, the cardiovascular effects of low- and high-dose propofol
      anesthesia (single bolus of 1.5 mg/kg in group A, 2.5 mg/kg in group C) were
      examined and compared with those of low- and high-dose thiopental (4 mg/kg in
      group B, 6.5 mg/kg in group D) (n = 10 patients per group). After induction of
      anesthesia with etomidate, all patients were ventilated with 70% nitrous oxide in
      oxygen. Peripheral arterial systolic blood pressure (SAP) and transesophageal
      echocardiographic short-axis measurements were used to calculate the end-systolic
      pressure-volume relationship (E) as an index of global myocardial contractility.
      In all groups SAP decreased significantly below baseline levels for the duration
      of the measurements (15 min after drug administration), except for the lower dose
      of thiopental, where SAP returned to baseline values within 10 min. Propofol at a
      dose of 1.5 mg/kg significantly decreased cardiac output (CO) (from 5.1 +/- 0.25
      [mean +/- SEM] to 4.2 +/- 0.23 L/min), stroke volume (SV) (from 64 +/- 3 to 56 +/
      3.6 mL), and the slope of E (from 71 +/- 3.5 to 65 +/- 4.2 mm Hg/mL) until 4 min
      after drug administration. The higher dose of propofol significantly decreased CO
      (from 5.1 +/- 0.29 to 4.1 +/- 0.26 L/min), SV (from 64 +/- 3 to 52 +/- 4.6 mL),
      and the slope of E (from 71 +/- 3.6 to 62 +/- 3.7 mm Hg/mL) until 10 min after
      drug administration.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1984374
TI  - A blinded comparison of noninvasive, in vivo phosphorus nuclear magnetic
      resonance spectroscopy and the in vitro halothane/caffeine contracture test in
      the evaluation of malignant hyperthermia susceptibility.
AB  - Malignant hyperthermia (MH) is a potentially fatal, anesthetic-induced syndrome.
      Currently, the only accurate means of diagnosing susceptibility to this syndrome
      is the testing of biopsied skeletal muscle for its contracture response to
      halothane and caffeine. A less invasive means of diagnosis is needed. The authors
      previously reported that MH-susceptible patients studied by in vivo phosphorus
      nuclear magnetic resonance (31P NMR) spectroscopy demonstrated a higher resting
      inorganic phosphate (Pi) to phosphocreatine (PCr) ratio in their skeletal muscle,
      as well as a slower postexercise recovery of PCr/Pi, when compared to normal
      controls. In the present blinded study, the authors compared in vivo 31P NMR
      determination of resting Pi/PCr and recovery rate of PCr/Pi in forearm muscles to
      in vitro halothane/caffeine contracture test results in 42 patients. Forty-three
      control subjects were studied to establish normal NMR values of resting Pi/PCr
      and recovery rate of PCr/Pi. Their findings were compared with those of 27
      patients shown to be MH-susceptible and 15 patients MH-negative by contracture
      testing. The MH-susceptible group had a significantly (P less than 0.005) higher
      resting Pi/PCr value (0.202 +/- 0.044) than either the MH-negative (0.152 +/-
      0.043) or the control (0.141 +/- 0.026) group. The MH-susceptible group also had
      a significantly (P less than 0.02) slower postexercise recovery rate of PCr/Pi
      (1.50 +/- 0.872 PCr.Pi-1.min-1) than either the MH-negative (2.11 +/- 1.07 PCr.Pi
      1.min-1) or control (2.25 +/- 0.828 PCr.Pi-1.min-1) group. Twenty-six of the 27
      MH-susceptible patients demonstrated abnormal NMR test results (a resting Pi/PCr
      greater than or equal to 0.18 or recovery rate less than 1.0 PCr.Pi-1.min-1), and
      13 of the 15 MH-negative patients had normal NMR results. Although neither NMR
      parameter alone was diagnostically reliable, an NMR test utilizing both
      parameters was quite accurate. The NMR test and contracture test demonstrated an
      overall agreement of 93% with a copositivity of 96% and conegativity of 87%. The
      sensitivity and specificity of the NMR test is estimated to be 98.8% +/- 11.8%
      and 95.3% +/- 20.3%, respectively. The role of 31P NMR in the diagnosis of MH
      susceptibility and possible mechanisms underlying the observations are discussed.

PMID- 1984376
TI  - Effects of halothane on impulse propagation in Purkinje fibers and at Purkinje
      muscle junctions: relationship of Vmax to conduction velocity.
AB  - Alterations in Purkinje-to-muscle conduction may play a role in the development
      of cardiac arrhythmias. We compared the effects of halothane on impulse
      propagation in Purkinje fibers with its effects on impulse propagation across the
      Purkinje-muscle (P-M) junction. In canine Purkinje fibers, halothane (3%)
      significantly depressed conduction (P less than 0.05). Exposure to halothane
      altered conduction velocity (theta) in a manner predicted by cable theory; a
      significant correlation was noted between depression of Vmax and depression of
      the square of conduction velocity (theta 2) in Purkinje fibers exposed to 3%
      halothane (n = 11, r = 0.78, P less than 0.01). Halothane (3%) significantly
      slowed impulse propagation across the P-M junction (P less than 0.05). Vmax and
      the square of apparent P-M conduction velocity were not significantly correlated
      (n = 7, r = 0.34, P = 0.45). The data demonstrate that alteration of active
      membrane properties can account for halothane's slowing of conduction in Purkinje
      fibers but not for its slowing of conduction across the P-M junction. The data
      also suggest that a reduction in cell-to-cell coupling may contribute to
      depression of Purkinje-to-muscle conduction by halothane.

PMID- 1984375
TI  - Cerebral blood flow autoregulation is preserved during cardiopulmonary bypass in
      isoflurane-anesthetized patients.
AB  - In 21 patients undergoing elective coronary artery bypass surgery, cerebral blood
      flow (CBF) was measured during hypothermic nonpulsatile cardiopulmonary bypass to
      test the hypothesis that isoflurane abolished the mean arterial pressure-CBF
      relation (pressure-flow autoregulation). Cerebral blood flow was determined by
      133Xe clearance. The patients were randomly divided into three groups according
      to anesthesia during cardiopulmonary bypass: group 1 received midazolam and
      fentanyl; group 2 received, in addition to midazolam and fentanyl, 0.6%
      isoflurane; and group 3 received, in addition to midazolam and fentanyl, 1.2%
      isoflurane. The groups were maintained at a constant temperature, PaO2, PaCO2,
      and pump flow during CBF measurements. Mean arterial pressure was increased by
      phenylephrine greater than or equal to 25% after the first CBF determination.
      Isoflurane decreased mean arterial pressure significantly (P less than 0.05) and
      was associated with lower CBF. Increasing the mean arterial pressure 29% in group
      1, 25% in group 2, and 34% in group 3 had no effect on CBF. We conclude that,
      within the range studied, pressure-flow CBF autoregulation is preserved during
      isoflurane anesthesia administered for cardiopulmonary bypass.

PMID- 1984377
TI  - Epidural morphine with butorphanol for postoperative analgesia after cesarean
      delivery.
AB  - Epidural morphine has been used more and more to provide long-lasting
      postoperative analgesia after cesarean delivery. However, the incidence of
      pruritus (20%-93%) and nausea (17%-60%) detract from the usefulness of epidural
      morphine. The purpose of this study was to evaluate, in 30 patients having
      epidural anesthesia for cesarean delivery, the analgesic efficacy and side
      effects when a combination of epidural morphine, a mu-receptor agonist, and
      butorphanol, a mu-receptor antagonist and kappa-receptor agonist, was
      administered. After clamping of the umbilical cord, patients received 4 mg
      epidural morphine with 3 mL of normal saline (group 1), 4 mg epidural morphine
      with 1 mg butorphanol and 2 mL of normal saline (group 2), or 4 mg epidural
      morphine with 3 mg butorphanol (group 3). Patients were monitored for 24 h after
      administration of the study medications. There were no significant differences
      between the groups in visual analogue pain scores, time to first analgesic
      request, respiratory rate, or Trieger dot test performance in the 24 h
      immediately after these epidural injections. There were three patients in group 1
      and one patient in group 2 who experienced oxygen saturations less than 90%. (No
      patients in group 3 developed an oxygen saturation less than 92%.) The patients
      in group 3 did not require treatment for pruritus or nausea, a response
      significantly different (P less than 0.001 and P less than 0.05, respectively)
      from group 1 or group 2.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1984378
TI  - Electrophysiologic effects of bupivacaine in the isolated rabbit heart.
AB  - To assess the direct electrophysiologic effects of bupivacaine, we examined the
      spontaneous sinus rhythm and induced rapid and premature atrial and ventricular
      pacing in 11 isolated rabbit hearts perfused in the Langendorff apparatus with
      varying concentrations (designated by []) of bupivacaine (control, n = 2; 0.3
      microgram/mL, n = 3; 1.5 micrograms/mL, n = 3; 3.0 micrograms/mL, n = 3). There
      was no change in sinus node automaticity or sinus node recovery time at any
      concentration and no evidence of abnormal automaticity. Depression of conduction
      was reflected by prolongation of the PR interval at the following concentrations:
      1.5 micrograms/mL (65.0 ms before, 96.6 ms after) and 3.0 micrograms/mL (61.6 ms
      before, 103.3 ms after) and increase in atrial and ventricular pacing thresholds
      at 3.0 micrograms/mL (atrial: 0.86-8.6 mA, ventricular: 2.0-10.0 mA). No
      spontaneous tachyarrhythmias occurred; 2:1 spontaneous atrioventricular block (n
      = 1) and a decrease in maximal paced rate with 1:1 anterograde or retrograde
      atrioventricular conduction were noted at all concentrations of bupivacaine. Thus
      bupivacaine did not change automaticity but had a depressant effect on conduction
      at the atrial, ventricular, and atrioventricular levels, providing a basis for
      clinically occurring atrioventricular block and reentrant arrhythmias.

PMID- 1984379
TI  - Isoproterenol corrects the effects of bupivacaine on the electrophysiologic
      properties of the isolated rabbit heart.
AB  - The purpose of this study was to test the hypothesis that isoproterenol could
      reverse bupivacaine toxicity. In eight isolated rabbit hearts an
      electrophysiologic evaluation was performed then repeated during infusion of
      bupivacaine (1 microgram/mL) alone and bupivacaine plus isoproterenol (1-2
      micrograms/mL). Bupivacaine alone increased electrocardiographic intervals (P
      wave, QRS complex, PR, AV, and QTc interval) and refractory periods of the
      myocardium and atrioventricular junction as well as the Wenckebach cycle and
      pacing thresholds. The addition of isoproterenol corrected partially or
      completely all bupivacaine-induced abnormalities, and decreased sinus cycle
      length, suggesting a potential therapeutic value in the treatment of bupivacaine
      intoxication.

PMID- 1984380
TI  - Cerebral effects of nitrous oxide when added to low and high concentrations of
      isoflurane in the dog.
AB  - The purpose of this canine study was to examine the cerebral vascular and
      metabolic effects of adding nitrous oxide to isoflurane from 1.4% expired (1 MAC)
      up to a concentration giving an isoelectric electroencephalogram (EEG). Cerebral
      blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2) were determined
      using a sagittal sinus outflow technique. At 1.4% expired isoflurane, 70% nitrous
      oxide increased CBF but had no effect on CMRO2. At 3.1% expired isoflurane, 70%
      nitrous oxide had no effect on either CBF or CMRO2. The latter concentration of
      isoflurane rendered the EEG isoelectric, but when nitrous oxide was added, EEG
      activity reappeared. To again produce an isoelectric EEG required an increase in
      the isoflurane concentration to 3.5% +/- 0.2% (with no further effect on CMRO2).
      The authors also found that at 1.4% isoflurane, 0.9 micrograms.kg-1.min-1 of
      angiotensin significantly decreased CMRO2 without any effect on CBF. It is
      concluded that nitrous oxide, when added to isoflurane concentrations ranging
      from 1.4% to 3.5% in the dog, increases CBF at the low but not the high
      isoflurane concentrations although it has no effect on CMRO2.

PMID- 1984381
TI  - Effective doses of epidural morphine for relief of postcholecystectomy pain.
AB  - Having previously established the effective dose of intrathecal morphine for
      relief of postcholecystectomy pain, we determined in this study the effective
      dose of epidural morphine for relief of postcholecystectomy pain in 154 patients
      given epidural injections of a placebo (group 1, n = 49), 2 mg morphine (group 2,
      n = 54), or 4 mg morphine (group 3, n = 51) intraoperatively mixed in 1.5%
      lidocaine. The percentage of patients who did not request an analgesic, 30 mg IM
      pentazocine, for relief of pain during the first 24 postoperative hours was
      significantly greater in groups 2 and 3 than in group 1. In patients who did need
      30 mg IM pentazocine postoperatively, the number of times pentazocine was
      administered was also significantly greater in group 1 than in groups 2 and 3.
      The percentage of patients developing respiratory depression or vomiting in the
      first 48 postoperative hours was similar in the three groups. Based on the
      present data and those we previously reported for intrathecal morphine, we
      conclude that an epidural morphine dose of 2-4 mg and an intrathecal morphine
      dose of 0.06-0.12 mg are equipotent for relief of postcholecystectomy pain.

PMID- 1984382
TI  - Effect of obesity on safe duration of apnea in anesthetized humans.
AB  - Obese patients have a decreased functional residual capacity and, hence, a
      reduced oxygen supply during periods of apnea. To determine whether obese
      patients are at greater risk of developing hypoxemia during induction of
      anesthesia than patients of normal weight, 24 patients undergoing elective
      surgical procedures were studied. Group 1 (normal) were within 20% of their ideal
      body weight. Group 2 (obese) were more than 20% but less than 45.5 kg over ideal
      body weight. Group 3 (morbidly obese) were more than 45.5 kg over ideal body
      weight. Patients were preoxygenated for 5 min or until expired nitrogen was less
      than 5%. After induction of anesthesia and muscle relaxation the patients were
      allowed to remain apneic until arterial saturation as measured by pulse oximetry
      reached 90%. The time taken for oxygen saturation to decrease to 90% was 364 +/-
      24 s in group 1, 247 +/- 21 s in group 2, and 163 +/- 15 s in group 3; these
      times are significantly different at P less than 0.05 between groups. Regression
      analysis of the data demonstrated a significant negative linear correlation (r = 
      0.83) between time to desaturation and increasing obesity. These results show
      that obese patients are at an increased risk of developing hypoxemia when apneic.

PMID- 1984383
TI  - Clinical evaluation of autotransfusion during liver transplantation.
AB  - The clinical suitability of intraoperative autotransfusion was evaluated in 25
      patients undergoing orthotopic liver transplantation using a Cell Saver #4
      (Haemonetics) with acid-citrate-dextrose anticoagulation. In the first 14
      patients (phase 1), biochemical, hematologic, coagulation, and semiquantitative
      bacteriologic studies were performed from the collected blood, processed blood,
      and patients' blood before and after 500 mL of autotransfusion. The acid-citrate
      dextrose solution produced adequate anticoagulation, and the system effectively
      removed most of the potassium, red blood cell fragments, plasma free hemoglobin,
      bilirubin, coagulation factors, platelets, and fibrin degradation products.
      Autotransfusion (500 mL) did not alter coagulation, electrolyte balance, and
      hematologic findings in recipients except for a clinically insignificant increase
      in plasma free hemoglobin. Seventeen of 56 samples of the collected blood or
      processed blood were positive for coagulase (-) Staphylococcus (occasional or
      rare), but blood cultures before and after autotransfusion were negative in all
      patients. In the next 11 patients (phase 2), a quantitative bacteriologic study
      was performed from the collected blood, processed blood, skin, bile duct stump,
      peritoneal cavity, and room air using a mock reservoir. The processed blood was
      not transfused. All blood cultures from the patients were sterile. However,
      coagulase (-) Staphylococcus or Bacillus sp was seen in two cultures from skin,
      three from the processed blood, and three from air, suggesting that room air and
      skin were the sources of contamination. When the patients of the two phases of
      study were compared, postoperative blood cultures were all sterile, and renal
      function was similar. Therefore, autotransfusion appears to be clinically
      acceptable during liver transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1984384
TI  - Methicillin-resistant staphylococcal colonization and infection in a long-term
      care facility.
AB  - OBJECTIVE: To determine the natural history of colonization by methicillin
      resistant Staphylococcus aureus (MRSA) among patients in a long-term care
      facility. We specifically sought to determine if MRSA colonization was predictive
      of subsequent infection. DESIGN: Cohort study. SETTING: Long-term Veterans
      Affairs Medical Center. PATIENTS: A total of 197 patients residing on two units
      were followed with regular surveillance cultures of the anterior nares. MAIN
      OUTCOME MEASUREMENT: The development of staphylococcal infection. RESULTS: Thirty
      two patients were persistent carriers of MRSA and 44 were persistent carriers of
      methicillin-susceptible strains (MSSA). Twenty-five percent of MRSA carriers had
      an episode of staphylococcal infection compared with 4% of MSSA carriers and 4.5%
      of non-carriers (P less than 0.01; relative risk 3.8; 95% CI, 2.0 to 6.4). The
      rate of development of infection among MRSA carriers was 15% for every 100 days
      of carriage. Using logistic regression analysis, persistent MRSA carriage was the
      most significant predictor of infection (P less than 0.001; odds ratio, 3.7).
      Seventy-three percent of all MRSA infections occurred among MRSA carriers.
      Isolates of MRSA from 7 patients were typed. Colonizing and infecting strains had
      the same phage type in all 7 patients and the same pattern of plasmid EcoRI
      restriction endonuclease fragments in 5 patients. CONCLUSIONS: Colonization of
      the anterior nares by MRSA predicts the development of staphylococcal infection
      in long-term care patients; most infections arise from endogenously carried
      strains. Colonization by MRSA indicates a significantly greater risk for
      infection than does colonization by MSSA. The results offer a theoretic rationale
      for reduction in MRSA infections by interventions aimed at eliminating the
      carrier state.

PMID- 1984385
TI  - Health, functional status, and employment of adult survivors of bone marrow
      transplantation.
AB  - OBJECTIVE: To determine the health, functional ability, and employment status of
      adults who survive bone marrow transplantation. DESIGN: Inception cohort study.
      SETTING: Patients who received transplants at a single referral-based center.
      PATIENTS: Adults of 18 years of age or older who had received bone marrow
      transplants at least 6 months previously and who were not in a life-threatening
      relapse were surveyed a mean of 47 months after transplant (median, 37 months;
      range, 6 to 149 months). Of 171 eligible patients, 157 were contacted and 135
      (86%) responded. MEASUREMENTS AND MAIN RESULTS: Patients completed a mailed
      survey. Medical records were also reviewed. Most patients (93%) reported they
      could do normal activities with minor or no physical problems (Karnofsky scores,
      greater than or equal to 80%). Global health was described as good to excellent
      by 67% of subjects. Most perceived social activities (80%) or physical functional
      abilities (67%) to be unimpaired or only slightly affected. Moderate or severe
      pain was uncommon (13%). Sixty-five percent had returned to full- or part-time
      employment, and one third of those who were not employed were attending school.
      Job discrimination and problems in obtaining insurance were reported by 23% and
      39%, respectively. Among those who had been employed before illness, loss of
      employment was associated with lower social functioning, chronic graft-versus
      host disease, greater job discrimination, and female gender using multivariate
      logistic regression. CONCLUSIONS: Most subjects surviving bone marrow transplant
      reported good to excellent health and functional ability. Three fourths were
      employed or enrolled in school. These outcomes are comparable to outcomes in
      survivors of cancer who received less intensive treatments.

PMID- 1984386
TI  - The safety and immunogenicity of a human immunodeficiency virus type 1 (HIV-1)
      recombinant gp160 candidate vaccine in humans. NIAID AIDS Vaccine Clinical Trials
      Network.
AB  - OBJECTIVE: To evaluate the safety and immunogenicity of a human immunodeficiency
      virus type 1 (HIV-1) recombinant envelope glycoprotein (rgp 160) candidate
      vaccine in humans. SUBJECTS: Healthy adults (72) who were seronegative for HIV-1
      were randomly assigned to one of four groups. INTERVENTIONS: The subjects were
      randomly assigned to receive 40 or 80 micrograms of rgp 160, 10 micrograms of
      hepatitis B vaccine, or placebo in three doses (on days 0, 30, and 180), with an
      elective, nonblinded administration of a fourth dose on day 540. MEASUREMENTS AND
      MAIN RESULTS: Neither clinical nor laboratory toxicity was encountered during a
      follow-up period exceeding 21 months. No effect of immunization was noted on
      lymphocyte counts, mitogenic responses, or delayed-type hypersensitivity. Serum
      antibody responses to HIV envelope proteins detected by Western blot were seen in
      30 of 33 subjects (91%; 95% CI, 71% to 97%) receiving either 40- or 80-micrograms
      doses of rgp160 and were most commonly of weakly reactive intensity. Responses
      were first noted by Western blot after the second dose. They markedly increased
      in frequency after the third dose and declined over the next 12 to 18 months. The
      administration of a fourth dose resulted in homologous neutralizing activity in
      sera from 5 to 24 subjects (21%; CI, 7% to 37%) as well as in complement-mediated
      antibody-dependent enhancement in sera from 6 of 24 subjects (25%; CI, 10% to
      42%). Antibody responses were detected by enzyme-linked immunosorbent assay
      (ELISA) less frequently than by Western blot, and these responses persisted for a
      shorter time. CONCLUSIONS: The administration of rgp160 was well tolerated and
      safe, resulted in a high rate of antibody response by Western blot after the
      administration of the third and fourth doses, and generated serum neutralizing
      activity and complement-mediated antibody-dependent enhancement in some subjects
      after the fourth dose.

PMID- 1984387
TI  - An increase in plasma cholesterol independent of thyroid function during long
      term amiodarone therapy. A dose-dependent relationship.
AB  - OBJECTIVE: To determine whether long-term amiodarone treatment is associated with
      a rise in plasma cholesterol, and, if so, to analyze its relation with thyroid
      function. DESIGN: Consecutive entry trial, including cardiac patients who
      initiated amiodarone medication but excluding those with abnormal thyroid
      function (defined as peak thyroid-stimulating hormone [TSH] response to
      thyrotropin-releasing hormone [TRH] less than 2.8 or greater than 22.0 mU/L)
      either before or during amiodarone treatment. PATIENTS: Twenty-three patients who
      remained euthyroid were studied. INTERVENTION: Oral administration of amiodarone
      (mean duration of treatment, 17 months; range, 6 to 30 months). MEASUREMENTS:
      Fasting plasma lipids, thyroid hormones, and peak TSH to TRH values were recorded
      before and every 6 months during amiodarone treatment. RESULTS: Plasma
      cholesterol gradually increased from 5.1 +/- 0.2 mmol/L before treatment to 6.9
      +/- 0.8 mmol/L after 30 months of amiodarone medication (P less than 0.001); the
      peak TSH response to TRH did not change. When age- and sex-specific reference
      values were applied, 30% of the patients had cholesterol values above the 75th
      percentile before treatment; this number rose to 69% after 2 years of treatment.
      The rise in plasma cholesterol was associated with an equal increase in
      apoprotein B. Plasma cholesterol was not related to the daily dose of amiodarone
      or to plasma concentrations of amiodarone, desethylamiodarone, thyroxine (T4),
      triiodothyronine (T3), or reverse triiodothyronine (rT3). Linear regression
      analysis indicated a positive relation between plasma cholesterol and the
      cumulative dose of amiodarone (r = 0.25, P less than 0.05). CONCLUSION: Long-term
      amiodarone treatment is associated with a dose-dependent increase in plasma
      cholesterol that is independent of thyroid function.

PMID- 1984388
TI  - Outcome of prophylactic therapy for idiopathic anaphylaxis.
AB  - OBJECTIVE: To determine the efficacy of a prophylactic regimen (prednisone, H1
      blockade, and sympathomimetic amine therapy) in patients with idiopathic
      anaphylaxis. DESIGN: Clinical trial before and after treatment. SETTING: Referral
      based allergy clinic at a major medical center. PATIENTS: Fifty-three patients
      with a history compatible with idiopathic anaphylaxis for at least 6 months
      before presentation to the allergy service and with subsequent management by the
      service for at least 6 months. INTERVENTIONS: Patients with frequent life
      threatening symptoms were treated with a prophylactic regimen. Patients with
      infrequent episodes of idiopathic anaphylaxis were only treated acutely for each
      episode of anaphylaxis. MEASUREMENTS AND MAIN RESULTS: The results favored
      prophylactic treatment with prednisone for patients who were classified as
      generalized-frequent in the clinical outcome measures of frequency (per patient
      per year) of episodes (mean before treatment, 7.31 +/- 6.46; after treatment,
      3.61 +/- 4.73; P less than 0.02) and emergency room visits (mean before
      treatment, 1.94 +/- 3.42; after treatment, 0.21 +/- 0.44; P less than 0.005) and
      for patients classified as angioedema-frequent in the frequency of episodes (mean
      before treatment, 14.93 +/- 15.89; after treatment, 2.58 +/- 2.18; P less than
      0.003) and emergency room visits (mean before treatment, 0.76 +/- 1.01; after
      treatment, 0.07 +/- 0.11; P less than 0.025). No statistically significant
      difference was found for patients classified as generalized-infrequent in the
      frequency of episodes (mean before treatment, 2.01 +/- 1.30; after treatment,
      1.36 +/- 1.79) or of the emergency room visits (mean before treatment, 0.56 +/-
      0.71; after treatment, 0.32 +/- 0.75) or for patients classified as angioedema
      infrequent in the frequency of episodes (mean before treatment, 1.94 +/- 1.55;
      after treatment, 2.03 +/- 2.16) or of emergency room visits (mean before
      treatment, 0.27 +/- 0.44; after treatment, 0.37 +/- 0.59). CONCLUSIONS:
      Prophylactic treatment with prednisone and H1 antihistamines with or without
      sympathomimetic amines improves clinical outcome in patients who are classified
      as idiopathic anaphylaxis-angioedema frequent and idiopathic anaphylaxis
      generalized frequent.

PMID- 1984389
TI  - Which clinical variables predict an abnormal double-contrast barium enema result?
AB  - OBJECTIVE: To determine the relations among patient history, symptoms, objective
      indicators, and abnormal double-contrast barium enema results in outpatients.
      PATIENTS AND SETTING: Seven hundred and ninety-four patients receiving care in a
      large multispecialty medical group. DESIGN: Physicians completed a form before
      ordering a double-contrast barium enema, listing information about patient
      history, symptoms, and objective findings, including the results of a complete
      blood count, stool hemoccult, and sigmoidoscopy. MEASUREMENTS AND MAIN RESULTS:
      Outcome measures were colon cancer and any abnormal finding. The results of 18.6%
      of the barium enemas were abnormal. The most frequent positive findings were of
      polyps (8.8%) and colon cancer (2.9%). Over 50% of the barium enemas were ordered
      solely on the basis of symptoms, yet there was no statistical correlation between
      symptoms and colon cancer or any positive finding. Using logistic regression,
      four variables were shown to be significant predictors of colon cancer (P less
      than 0.05): abnormal sigmoidoscopy, iron deficiency anemia, positive stool
      hemoccult results, and relevant history. The respective odds ratios of these
      variables were 3.76 (95% CI, 2.89 to 4.90); 2.86 (CI, 2.13 to 3.74); 1.87 (CI,
      1.46 to 2.39); and 1.91 (CI, 1.44 to 2.52), respectively. In a patient without
      any of these indicators, the predicted probability of having colon cancer was
      only 0.7%. In a patient with at least two objective indicators, the probability
      of having colon cancer was greater than 15%. CONCLUSIONS: Symptoms without
      objective indicators or pertinent risk factors do not correlate with an abnormal
      double-contrast barium enema result. Objective indicators are useful predictors
      of an abnormal barium enema result, particularly when looking for colon cancer.

PMID- 1984390
TI  - Low-probability lung scan findings: a need for change.

PMID- 1984391
TI  - Rapid reversal of acute psychosis in the Cushing syndrome with the cortisol
      receptor antagonist mifepristone (RU 486).

PMID- 1984392
TI  - Corticosteroid therapy for diffuse alveolar hemorrhage in autologous bone marrow
      transplant recipients.

PMID- 1984393
TI  - Caffeine and cardiac arrhythmias.
AB  - PURPOSE: To review the evidence supporting the belief that caffeine causes
      cardiac arrhythmias. DATA SOURCES: Studies published since 1982 identified
      through computerized searches of MEDLINE, TOXLINE, and Chemical Abstracts and a
      review of bibliographies of relevant articles on the subject of caffeine and
      cardiac arrhythmias. STUDY SELECTION: All clinical studies examining caffeine as
      a cause of cardiac arrhythmias and a selection of basic science experiments to
      illustrate caffeine's effects in vitro. DATA EXTRACTION: Study quality was
      assessed and all available clinical data pertaining to caffeine as a cause of
      arrhythmias were summarized. RESULTS OF DATA ANALYSIS: In one electrophysiologic
      study, caffeine was associated with an increased susceptibility to provoked
      cardiac arrhythmias. In five placebo-controlled trials, caffeine in doses up to
      500 mg daily (equivalent to 5 to 6 cups of coffee) did not increase the frequency
      or severity of ventricular arrhythmias. One large epidemiologic study reported an
      increase in the frequency of ventricular extrasystoles in persons consuming 9 or
      more cups of coffee daily. CONCLUSION: Moderate ingestion of caffeine does not
      increase the frequency or severity of cardiac arrhythmias in normal persons,
      patients with ischemic heart disease, or those with pre-existing serious
      ventricular ectopy.

PMID- 1984394
TI  - Limiting resuscitation: emerging policy in the emergency medical system.
AB  - Patients, families, and physicians frequently decide that a hospitalized patient
      will forgo cardiopulmonary resuscitation and document this decision with a do-not
      resuscitate (DNR) order. In community settings (home, nursing home, hospice),
      these orders may conflict with paramedics' standing orders to provide
      cardiopulmonary resuscitation whenever it is medically indicated. We did a
      nationwide telephone survey of state offices for coordination of emergency
      medical services (EMS) to see how the states deal with this potential conflict.
      We identified eight states that have specific policies enabling EMS personnel to
      accept DNR orders for patients being transported by ambulance. State officials
      identified administrative complexities and legal concerns as the primary barriers
      to enacting prehospitalization DNR policies. We also identified 21 local EMS
      systems that have developed policies for accepting orders to withhold life
      sustaining treatment. Four types of policy models, characterized according to
      procedure for validating DNR orders and telephone accessing the EMS system, show
      that regulatory reform can address policy barriers in the absence of enabling
      legislation.

PMID- 1984395
TI  - Ethics consultation: skills, roles, and training.
AB  - A clinical ethics consultant gathers information firsthand at the patient's
      bedside. The consultant's special clinical skills include the ability to identify
      and analyze ethical problems; use reasonable clinical judgment; communicate
      effectively; negotiate and facilitate negotiations; and teach others how to
      construct their own ethical frameworks for medical decision making. Appropriate
      roles for the consultant include those of professional colleague, negotiator,
      patient and physician advocate, case manager, and educator. The training
      necessary for an ethics consultant includes substantial patient care experience,
      instruction in health care law and moral reasoning, and preparation in medical
      humanism. We favor a clinical model for ethics consultation. When urgent care is
      needed, other consultants promptly see the patient; the clinical ethics
      consultant can be expected to do the same.

PMID- 1984396
TI  - AIDS vaccines: progress and unmet challenges.

PMID- 1984397
TI  - Methicillin-resistant Staphylococcus aureus: do we just have to live with it?

PMID- 1984398
TI  - Screening for colorectal cancer.

PMID- 1984399
TI  - Calcium-channel antagonists reduce renal protein excretion.

PMID- 1984400
TI  - Caregiving in Alzheimer dementia.

PMID- 1984401
TI  - Predicting suicide.

PMID- 1984402
TI  - Transference.

PMID- 1984403
TI  - Medical futility.

PMID- 1984405
TI  - Clinical prediction rules.

PMID- 1984404
TI  - Population and the environment.

PMID- 1984406
TI  - Molecular cloning of transcripts that accumulate during the late G1 phase in
      cultured mouse cells.
AB  - To identify previously undetected genes that might be involved in later stages of
      the transition from a quiescent state (G0) to the DNA synthetic phase (S) of
      murine cells, we set out to isolate cDNA clones derived from mRNAs that appear
      late in G1 phase in serum-stimulated cells. A lambda-cDNA library was prepared
      using poly(A)+ RNA from chemically transformed Balb/c 3T3 cells (BP/A31) that had
      been brought to quiescence and subsequently stimulated for 12 h with serum. From
      the first screening of approximately 21,000 recombinant phage plaques, about 100
      clones were isolated that hybridized to a single-stranded cDNA pool derived from
      stimulated-cell RNA but not to DNAs made from resting-cell RNA. Eventually, six
      different clones were identified. The mRNAs from five of these genes increased
      gradually during the G0 to S transition, in contrast to the "immediate-early"
      rise of c-myc mRNA or the later rise of thymidine kinase mRNA. These six clones
      were sequenced and compared to the GenBank database. Clones LG-80, LG-2, and LG
      69 are highly homologous to beta-actin, lactate dehydrogenase, and alpha-tubulin.
      Clones LG-5, LG-61, and LG-74 had no significant homologies to known sequences. A
      subtractive cDNA library was used to isolate two additional clones, Sub-S1 and
      Sub-S2; these have homologies to enolase and ribosomal protein L32. Additional
      studies that examine the function and regulation of these newly identified "late
      response" genes in the pre-DNA synthesis pathway are in progress.

PMID- 1984407
TI  - Genes for collagen types I, IV, and V are transcribed in HeLa cells but a
      postinitiation block prevents the accumulation of type I mRNA.
AB  - Collagen mRNA synthesis in HeLa cells was evaluated by in vitro transcription of
      type I collagen DNA, nuclear run-on studies, and steady-state mRNA analysis. Type
      I collagen mRNA was accurately initiated by HeLa cell RNA polymerase II in
      nuclear extracts, and run-on analysis indicted that mRNAs for collagen types
      alpha 1(I), alpha 2(I), alpha 1(III), alpha 1(IV), and alpha 2(V) were
      synthesized in HeLa cells. However, on assessing the steady-state levels of mRNAs
      of collagen types alpha 1(I), alpha 2(I), alpha 1(IV), and alpha 2(V), no type I
      mRNA was found in HeLa cells while types alpha 1(IV) and alpha 2(V) collagen
      mRNAs were observed. These results suggest that a postinitiation process prevents
      the accumulation of type I collagen mRNAs in HeLa cells. Persistence of types IV
      and V collagen mRNAs is consistent with the involvement of types IV and V
      collagen in adhesion of HeLa cells to glass or plastic.

PMID- 1984408
TI  - Highly synchronous culture of fibroblasts from G2 block caused by staurosporine,
      a potent inhibitor of protein kinases.
AB  - The effect of staurosporine, a potent microbial inhibitor of protein kinases, on
      the cell cycle of cultured fibroblast cells was investigated. A low concentration
      of staurosporine (1-10 ng/ml) blocked the cell cycle of rat 3Y1 fibroblasts at
      the early G1 phase within 2 h after serum stimulation. On the other hand, a
      higher concentration of the drug (100 ng/ml) caused the specific G2 block. Both
      of these blocks were reversible. After release from the G2 block, highly
      synchronous transition to M phase was observed and both nuclear and cell
      divisions were completed within 180 min. This reversible G2 block showed a clear
      contrast to those by the other G2 arresters, trichostatin A and leptomycin B,
      which formed proliferative tetraploid cells after release by entering the cells
      into a new S phase without passage through M phase. The presence of trichostatin
      A or leptomycin B did not interfere with this synchronous progression through
      G2/M phases, suggesting that the arrest point of staurosporine was present in
      late G2 phase following those of trichostatin A and leptomycin B.

PMID- 1984409
TI  - Correlation of metabolic stability and altered quaternary structure of
      oncoprotein p53 with cell transformation.
AB  - The phosphoprotein p53 seems to be implicated in various processes connected with
      cell transformation and in particular with the regulation of cell cycle and
      probably DNA replication. In the present paper we have analyzed two sets of
      closely related cell lines expressing the same p53 which exhibited either a
      nontransformed or a transformed phenotype. These cell lines were used to study
      biochemical properties of the p53 protein which might be correlated with cell
      transformation. We found a positive correlation among an elevated stability of
      p53, the formation of high-molecular-weight forms of p53, and the transformed
      phenotype of the corresponding cell lines. Furthermore, these data indicate that
      self-aggregation prevents p53 from rapid degradation. By a comparative analysis
      of the stability and oligomerization properties of mutant p53 and wild-type p53,
      we could demonstrate that elevated stability and self-aggregation of p53 are
      correlated with the transformed phenotype of the cells and independent of a
      particular mutation in the p53 gene.

PMID- 1984410
TI  - Inhibition of cell proliferation by the cholecystokinin antagonist L-364,718.
AB  - Specific cholecystokinin (CCK) receptor and gastrin receptor antagonists were
      used to assess what role, if any, these receptors have in autocrine cell growth.
      Although the cholecystokinin receptor antagonist, L-364,718, inhibited cell
      proliferation in a broad spectrum of cell lines, the gastrin antagonist, L
      365,260, had no effect on cell proliferation. In addition neither added
      gastrin17, nor sulfated cholecystokinin8, could reverse the inhibitory action of
      L-364,718. It is proposed that L-364,718 inhibits cell proliferation
      independently of classical gastrin/CCK receptors.

PMID- 1984411
TI  - Retention of the mitochondrial probe rhodamine 123 in normal lymphocytes and
      leukemic cells in relation to the cell cycle.
AB  - The cationic fluorochrome rhodamine 123 (R123) is specifically taken up by
      mitochondria of live cells where it is retained due to the mitochondrial
      transmembrane potential. After pulse exposure of human normal quiescent or
      proliferating lymphocytes, human lymphocytic leukemic MOLT cells, and mice
      leukemic L1210 cells to 10 micrograms/ml of R123, the dye release was studied
      using flow cytometry. Two distinct phases of R123 release, each following first
      order kinetics, were apparent; the half-time of retention for the rapidly and
      slowly released fractions of R123 was 0.8-1.1 and 2.8-4.2 h, respectively.
      Simultaneous supravital cell staining with R123 and Hoechst 33342 made it
      possible to correlate retention of R123 with cell position in the cell cycle. No
      significant differences were observed in the rate of R123 release from cells in
      G1 vs S or vs G2 + M phases of the cycle. The data rule out a possibility that
      the release of R123 is due to periodic depolarization of the mitochondria in the
      cell as may be postulated by cell cycle models that assume a transient passage of
      cells through resting phase following division. The observed similar rates of
      R123 release regardless of cell type or cell cycle phase suggest that the factors
      affecting the exchange are similar in normal lymphocytes vs leukemic cells and
      unrelated to cell proliferation rate or phase of the cell cycle. Two distinct
      rates of R123 release indicate the presence of two kinds of binding sites
      differing in affinity to the dye.

PMID- 1984412
TI  - Yeast cell-free nuclear protein import requires ATP hydrolysis.
AB  - Saccharomyces cerevisiae nuclear proteins are shown to localize specifically to
      isolated yeast nuclei under conditions selective for nuclear proteins. Nuclear
      association is time- and temperature-dependent, requires ATP hydrolysis, and is
      abolished by protease pretreatment of nuclei. The nucleus-localized protein is
      translocated across the nuclear envelope as determined by inaccessibility to
      externally added immobilized protease. This cell-free system, consisting of
      components from an organism amenable to genetic analysis, will facilitate the
      study of the poorly understood mechanism of nuclear protein localization. The
      finding that ATP hydrolysis is required for nuclear import is the most direct
      evidence that nuclear localization is energy-dependent.

PMID- 1984414
TI  - Alterations in the expression of muscle-specific genes mediated by troponin C
      antisense oligodeoxynucleotide.
AB  - The effectiveness of an antisense oligodeoxynucleotide to troponin C (TnC) mRNA
      in blocking expression of TnC in differentiated chicken myotubes was examined. An
      18-nucleotide-long sequence common to both fast and slow isoforms of TnC mRNAs
      was chosen as the target sequence. The oligomer was found to be efficiently taken
      up by myotubes. However, the intracellular half-life of the oligomer was found to
      be only 3 h. Results of studies using different concentrations of oligomer for 3
      h in the culture medium showed that compared to the untreated control culture,
      myotubes incubated with 20 microns antisense oligomer showed a 30% reduction in
      the steady-state level of TnC mRNAs. An increase of incubation period to 12 h
      with additions of fresh culture medium containing 20 microns antisense oligomer
      every 3 h failed to produce any further reduction of TnC mRNA level. Concomitant
      to the decrease of TnC mRNAs in antisense oligomer-treated cells, the steady
      state levels of alpha-actin and alpha-tropomyosin mRNAs were also reduced by
      approximately 20 to 40%. Analysis of the homology of the sense sequence of this
      oligomer with that of alpha-actin and alpha-tropomyosin mRNAs suggested that
      reduction in the level of alpha-actin and alpha-tropomyosin mRNAs was not due to
      direct hybridization of the antisense oligomer to these mRNAs. Comparison of TnC
      polypeptide synthesis in untreated and oligomer-treated myotubes showed
      approximately 70% reduction of fast TnC polypeptide synthesis in antisense
      oligomer-treated cells. In contrast, slow TnC polypeptide synthesis was not
      significantly reduced in treated cells. Similarly, alpha-actin and alpha
      tropomyosin polypeptide synthesis remained close to the level of untreated cells.
      Furthermore, analysis of transcription of various muscle-specific mRNAs showed
      increased synthesis of both TnC and alpha-tropomyosin mRNAs in antisense oligomer
      treated myotubes. On the other hand, synthesis of actin mRNAs was not altered by
      this treatment. These results showed that antisense oligomer was effective in
      significantly reducing TnC polypeptide synthesis in chicken myotubes.
      Furthermore, these results suggest that treatment of myotubes with antisense
      oligomer to TnC mRNA may have triggered a complex array of compensatory
      processes.

PMID- 1984415
TI  - A Mr 72K cell surface concanavalin A binding glycoprotein is specifically
      involved in the spreading of chick embryo fibroblasts onto laminin substrate.
AB  - In the present study we have identified a 72-kDa cell surface concanavalin A
      binding glycoprotein (cbg 72) involved in the chick embryo fibroblast (CEF)
      adhesion onto laminin (LM) substrate. The cbg 72 was shown to interact
      specifically with immobilized laminin and to be resistant to Triton X-100
      extraction when CEF were plated on laminin substrate but not on fibronectin (FN)
      substrate. This behavior suggested that cbg 72 could interact with cytoskeletal
      elements during cell spreading onto LM. This assumption is also in good agreement
      with the partitioning of cbg 72 in Triton X-114. Isolated cbg 72 specifically
      inhibited CEF spreading onto LM after their initial attachment, whereas cbg 72
      did not impair the spreading of CEF onto FN. These data provide a molecular
      explanation to the inhibition of CEF spreading onto LM observed in the presence
      of the lectin concanavalin A (P. Codogno, M.-A. Doyennette-Moyne, J. Botti, and
      M. Aubery, 1988, J. Cell Physiol. 136, 463-470). Moreover, these results provide
      evidence for the role of a novel LM binding glycoprotein during the adhesion of
      mesenchymal derived cells. The relationship between cbg 72 and other known cell
      surface LM binding sites or receptors is discussed.

PMID- 1984413
TI  - Calcium mobilization by cadmium or decreasing extracellular Na+ or pH in coronary
      endothelial cells.
AB  - Replacing extracellular Na+ with choline transiently increased cytoplasmic free
      Ca2+ ([Ca2+]i) more than 5-fold in coronary endothelial cells. Removing external
      Na+ stimulated 45Ca2+ efflux approximately 4-fold and influx approximately 1.7
      fold. The stimulation of efflux was independent of extracellular Ca2+ and the
      osmotic Na+ substitute. The release of stored Ca2+, rather than Ca2+ influx via
      Na(+)-Ca2+ exchange, probably causes the increase in [Ca2+]i and 45Ca2+ efflux.
      Cadmium or decreasing external, not intracellular, pH transiently increased
      [Ca2+]i. Cd2+ and some other divalent metals also stimulated 45Ca2+ efflux. The
      potency order of the metals that stimulated efflux was Cd2+ greater than CO2+
      greater than Ni2+ greater than Fe2+ greater than Mn2+. Incubating the cells with
      Zn2+ prior to assaying efflux in the absence of Zn2+ strongly inhibited the
      stimulation of 45Ca2+ efflux by Cd2+, pH 6, and the removal of external Na+
      without affecting the stimulation of efflux by ATP. These findings support the
      hypothesis that certain trace metals or decreasing external Na+ or pH trigger the
      release of stored Ca2+ by stimulating a cell surface "receptor."

PMID- 1984416
TI  - Expression of plant genes in transfected mammalian cells: accumulation of
      recombinant preLHCIIb proteins within cytoplasmic inclusion bodies.
AB  - Transfection of the monkey COS-7 cells with an expression vector bearing the
      Lemma gibba LHCIIb AB30 or AB19 genes led to the synthesis of the LHCIIb
      polypeptide precursors (preLHCIIb). This was inferred mainly from Western blot
      analysis which has revealed the appearance of a single immunoprecipitation band
      following the use of three different preparations of anti-LHCIIb antibodies.
      Synthesis of the precursor polypeptides, not the mature processed LHCIIb protein,
      was evident from the molecular weight of the newly synthesized protein, inferred
      from its position in the gel. Expression of the AB30 and AB19 genes was also
      evident from the appearance of specific transcripts only in transfected cells.
      Immunofluorescence observations revealed the appearance of distinct fluorescent
      spots in about 1-2% of the transfected cells. The same was observed following
      immunogold staining and electron microscopy studies, which revealed a specific
      association of gold particles with amorphous structures only in transfected
      cells. The preLHCIIb synthesized by transfected COS-7 cells was insoluble in a
      variety of detergents and could be solubilized only by 8 M urea or 0.1 N NaOH.
      These properties are characteristic of proteins accumulating within inclusion
      bodies of prokaryotes.

PMID- 1984417
TI  - Cell hypertrophy and type X collagen synthesis in cultured articular
      chondrocytes.
AB  - Articular cartilage is a permanent tissue whose cells do not normally take part
      in the endochondral ossification process. To determine whether articular
      chondrocytes possess the potential to express traits associated with this process
      such as cell hypertrophy and type X collagen, chondrocytes were isolated from
      adult chicken tibial articular cartilage and maintained in long-term suspension
      cultures. As a positive control in these experiments, we used parallel cultures
      of chondrocytes from the caudal portion of chick embryo sternum. Both articular
      and sternal chondrocytes readily proliferated and progressively increased in size
      with time in culture. Many had undergone hypertrophy by 4-5 weeks. Analysis of
      medium-released collagenous proteins revealed that both articular and sternal
      chondrocytes initiated type X collagen synthesis between 3 and 4 weeks of
      culture; synthesis of this macromolecule increased with further growth.
      Immunofluorescence analysis of 5-week-old cultures showed that about 15% of
      articular chondrocytes and 30% of sternal chondrocytes produced type X collagen;
      strikingly, there appeared to be no obvious relationship between type X collagen
      production and cell size. The results of this study show that articular
      chondrocytes from adult chicken tibia possess the ability to express traits
      associated with endochondral ossification when exposed to a permissive
      environment. They suggest also that the process of cell hypertrophy and
      initiation of type X collagen synthesis are independently regulated both in
      articular and sternal chondrocytes.

PMID- 1984418
TI  - Dystrophin is tightly associated with the sarcolemma of mammalian skeletal muscle
      fibers.
AB  - Sarcolemmal vesicles with right-side-out configuration were prepared from normal
      fresh human and rabbit skeletal muscle bundles by incubation in 140 mM KCl
      solution containing collagenase. The vesicles were used to examine the
      association of dystrophin, the protein product of the Duchenne muscular dystrophy
      gene, with the sarcolemma. Western blot analysis, indirect immunofluorescence,
      and immunoperoxidase staining using specific antibodies raised against the N
      terminal and the C-terminal domains show that dystrophin remains associated with
      the membrane of sarcolemmal vesicles. Indirect immunofluorescence microscopy
      using permeabilized and unpermeabilized vesicles indicated that both the N
      terminus and the C-terminus of dystrophin are localized to the cytoplasmic
      surface of the sarcolemma. These results suggest that dystrophin has much
      stronger attachment to the surface membrane than it has to the internal domain of
      skeletal muscle fibers. Sarcolemmal vesicles thus represent a new system for
      studying the function of dystrophin and the molecular basis of its association
      with the sarcolemma.

PMID- 1984419
TI  - Oligonucleotides antisense to catalytic subunit of cyclic AMP-dependent protein
      kinase inhibit mouse mammary epithelial cell DNA synthesis.
AB  - Mouse mammary epithelial cells were plated onto 24-well culture plates (50,000
      per well), allowed to attach and serum starved for 24 h. Following serum
      starvation, DNA synthesis was induced by the addition of 10% fetal calf serum and
      determined by a 1-h pulse with [3H]thymidine from 17 to 18 h after serum
      addition. Addition of oligonucleotides antisense to the translation start region
      of cyclic AMP-dependent protein kinase (kinase A) mRNA inhibited thymidine
      incorporation into DNA (total or percentage of cells incorporating thymidine, as
      measured by autoradiography). This inhibition was apparent whether compared to
      controls with no oligonucleotide addition, sense oligonucleotides, or mismatch
      oligonucleotides. Enzymatic assays indicated that the antisense oligonucleotides
      lowered kinase A activity in cells. Time course studies indicated that the
      inhibition in DNA synthesis was not an artifact of the time at which DNA
      synthesis was estimated. Long-term (4 day) cultures indicated that effects on
      induction of DNA synthesis were reflected in long-term cell proliferation.

PMID- 1984420
TI  - Vectorial transcytosis of immunoglobulin G by human term trophoblast cells in
      culture.
AB  - Trophoblast cells were grown on filters that allow access to apical and basal
      surfaces of cells. Using this experimental system, IgG transport was shown to be
      specific and to occur primarily in the apical to basal direction. This transport
      was time- and temperature-dependent, with approximately 10% of added IgG
      appearing on the basal side within a 60-min incubation at 37 degrees C. Other
      substances such as heparin were transported only minimally, whereas horseradish
      peroxidase was transported to the same degree in both directions. Greater than
      90% of the transported IgG was precipitable by trichloroacetic acid and 81% was
      capable of binding to protein G. Such a rapid transport of large amounts of IgG
      in trophoblast cells is consistent with a receptor-mediated process of
      transcytosis.

PMID- 1984421
TI  - Induction and disappearance of DNA strand breaks in human peripheral blood
      lymphocytes and fibroblasts treated with methyl methanesulfonate.
AB  - The induction and disappearance of DNA single-strand breaks (SSB) in human
      peripheral blood lymphocytes (PBL) and fibroblasts exposed to methyl
      methanesulfonate (MMS) were investigated by using the alkaline filter elution
      assay. In the two cell types, identical amounts of SSB were induced during a 45
      min treatment with a given dose of MMS. In quiescent PBL only 9 +/- 4% (mean +/-
      SD) of the induced SSB had disappeared at 1 h after exposure, whereas in
      phytohemagglutinin-stimulated PBL, 23 +/- 12% disappeared within the same repair
      period. The percentage SSB disappearance in confluent fibroblasts was 25 +/- 2%
      at 1 h after exposure. As in PBL, the percentage SSB disappearance in fibroblasts
      appeared to be proliferation-dependent; actively dividing fibroblasts removed 50
      +/- 12% of the MMS-induced SSB during the 1-h repair period. The accumulation of
      SSB in PBL, but not in fibroblasts, during MMS exposure in the presence of the
      excision-repair inhibitor 1-beta-D-arabinofuranosylcytosine indicated the
      utilization of different repair pathways in these two cell types. The generally
      lower rate of disappearance of MMS-induced SSB in PBL as compared to fibroblasts
      correlated with an increased loss of cell viability, measured by determining the
      incorporation of [3H]thymidine.

PMID- 1984422
TI  - Fractionation of jelly substance of the sea urchin egg and biological activities
      to induce acrosome reaction and agglutination of spermatozoa.
AB  - Jelly coat substance surrounding the egg of the sea urchin, Hemicentrotus
      pulcherrimus, was fractionated by gel filtration and three fractions designated
      A, B, and C were obtained which mainly consisted of fucose sulfate, sialic acid,
      and protein, respectively. The biological activities of the fractions were
      examined for induction of acrosome reaction (AR) and agglutination of
      spermatozoa. Only fraction A, a fucose-rich glycoprotein fraction, had activities
      for both AR and agglutination. Fraction A was found to lose activity for AR but
      to retain activity for agglutination after pronase digestion. Pronase-digested
      fraction A was further fractionated by the same gel filtration and three
      fractions designated P1, P2, and P3 were obtained, which contained mainly fucose
      sulfate, sialic acid, and proteinous material, respectively. These fractions had
      no activity for AR but activity for agglutination resided in fraction P1, a
      fucose sulfate fraction. Furthermore, beta-elimination of the jelly substance was
      carried out to separate protein and fucose sulfate polysaccharide and three
      fractions designated E1, E2, and E3 were obtained by gel filtration, of which the
      fucose-rich fraction (E1) exhibited activities for both AR and agglutination, and
      the sialoprotein fraction (E2) retained activity only for AR. However, the
      activity for AR of both fractions was destroyed by pronase digestion. These
      results suggest that activity to induce AR resides in the protein moiety of
      fucose-rich glycoprotein and activity for agglutination resides in the fucose
      sulfate polysaccharide moiety of the same glycoprotein of the jelly substance.

PMID- 1984423
TI  - Selective conversion and esterification of monohydroxyeicosatetraenoic acids by
      human vascular smooth muscle cells: relevance to smooth muscle cell
      proliferation.
AB  - 5-, 12-, and 15-hydroxyeicosatetraenoic acid (HETE), lipoxygenase metabolites of
      arachidonic acid that may modulate cell proliferation, were examined for their
      ability to affect the [3H]thymidine incorporation of human umbilical artery
      smooth muscle cells. We found that these hydroxy fatty acids inhibited the serum
      induced [3H]thymidine incorporation of growth-arrested vascular smooth muscle
      cells in a similar dose-dependent manner. The inhibitory effect was dependent on
      the serum concentration used to stimulate cell growth. The higher the serum
      concentration, the lower the inhibitory effect of the HETE. In parallel
      experiments, the incorporation of HETEs into lipids of the smooth muscle cells
      was examined. After 20 h of incubation, we found that in the presence of 0.4%
      serum 70% of 3H-labeled 5-HETE was esterified into human vascular smooth muscle
      cell lipids. Twelve and eight percent, respectively, of 12- and 15-HETE were
      incorporated into smooth muscle cell lipids. Furthermore, we found that during
      the 20-h incubation of human umbilical artery smooth muscle cells with 12- and 15
      HETE, these compounds were converted into metabolites with a chromatographic
      behavior on HPLC similar to that of diHETEs. 5-HETE was not converted into these
      polar metabolites. Increasing the serum concentration resulted in a decreased
      metabolism of all HETEs tested. Thus, the distinct differences between the
      metabolism of different HETEs by vascular smooth muscle cells does not reflect
      the proliferation inhibitory effect of these HETEs.

PMID- 1984424
TI  - Abnormal perikaryal immunoreactivity to the phosphorylated heavy neurofilament
      unit in intracerebral basal forebrain transplants.
AB  - Grafts of Embryonic Day 14-15 basal forebrain tissue (medial septal/diagonal band
      nuclei) were transplanted into an aspirative fimbria-fornix cavity or the
      hippocampus of young adult rats. After extended periods of survival (1 and 2
      years) the grafts were examined with immunocytochemical probes to identify
      specific types of neurons and assess the (spatial) distribution of the
      phosphorylated heavy neurofilament protein. Subpopulations of the long-term
      transplanted neurons expressed immunoreactivity to choline acetyl-transferase
      (CAT) and the low-affinity nerve growth factor receptor (192-IgG). Axons from the
      grafted neurons, visualized with the monoclonal antibody RT97 to the Mr 200,000
      phosphorylated neurofilament unit, were observed to extend over the surfaces of
      the brain and connect with the host hippocampus. In subgroups of neurons without
      apparent axonal connections to the hippocampus, a change from axonal to cell body
      RT97 immunoreactivity was evident. A population of these neurons with abnormal
      neurofilament immunostaining in the soma was simultaneously identified as
      cholinergic with the CAT antibody. These studies indicate that abnormal changes
      can develop in the cytoskeleton of neurons in long-term intracerebral septal
      transplants. Although the reasons for this type of neurofilament modification in
      the grafted neurons are unknown, inappropriate terminal connections may be an
      important factor in the expression of this cytoskeletal change.

PMID- 1984425
TI  - Fetal nigral grafts in the anterior eye chamber of adult rats: a long-term
      morphological study.
AB  - Substantia nigral grafts of 16 and 17 gestation days showed phenotypic
      characteristics in the anterior eye chamber of adult rats until the third month
      after transplantation. Thereafter by the sixth month a number of neurons showed
      somal and dendritic thickening, reduced population of endoplasmic reticulum,
      increase in lysosomes, and clear areas devoid of organelles, indicating age
      changes. These changes were progressive and affected more neurons by the end of 1
      year, the longest period studied. The observations suggest that the maturation of
      nigral neurons is independent of specific afferent input, whereas target
      influence is necessary for the continued maintenance of the mature neurons. All
      the synapses observed in the transplant were of the asymmetric variety,
      reminiscent of the few intrinsic synapses of the intact nigra. This suggested
      establishment of mutual connectivity among the transplanted neurons in the
      absence of a target and the type of synapse formed may have been influenced by
      the local environment. Large glial processes, very prominant during the 4- to 6
      month period became less significant afterward but continued to be present until
      the end of the period studied. Though there was no morphological evidence of
      lymphocytic infiltration, this might suggest an immunologic reaction.

PMID- 1984426
TI  - Inactivity-induced motor nerve terminal sprouting in amphibian skeletal muscles
      chronically blocked by alpha-bungarotoxin.
AB  - There is a positive correlation between contractile inactivity and the initiation
      of motor neuron sprouting. However, the exact mechanism responsible for this
      neuronal growth remains obscure. In a previous study (M. M. Wines and M.S.
      Letinsky, 1988, J. Neurosci. 8: 3909-3919) we investigated this phenomenon by
      inducing chronic contractile inactivity of an amphibian muscle by exposure to
      formamide and found that motor neuron sprouting occurs in the presence of normal
      pressynaptic transmitter release and propagated muscle fiber action potentials.
      The present study investigates motor neuron sprouting in response to inactivity
      produced when neuromuscular transmission is blocked by chronic exposure to alpha
      bungarotoxin (alpha-BTX). The alpha-BTX-induced muscle paralysis was maintained
      for 1-63 days by repetitive application of the toxin to the cutaneous pectoris
      muscle of adult Rana pipiens. During the chronic alpha-BTX treatment end-plate
      potentials were reduced below threshold, which therefore removed both muscle
      fiber action potentials and contractile activity. Our findings showed only
      terminal sprouting. Also, higher sprouting frequencies (up to 100% of the
      observed terminals) were observed after chronic alpha-BTX treatment, compared to
      the sprouting response induced by formamide treatment. In view of our earlier
      formamide results, these observations suggest that the inhibition of the
      postsynaptic acetylcholine response, and consequently inhibition of muscle fiber
      electrical and contractile activity, produces a stronger stimulus to motor neuron
      sprouting than the presence of contractile inactivity alone coupled with normal
      synaptic transmission and muscle electrical activity.

PMID- 1984427
TI  - Experimentally-induced neuron loss in the locus coeruleus of adult rats.
AB  - Systemic administration of the noradrenergic neurotoxin N-(2-chloroethyl)-N-ethyl
      2-bromobenzylamine (DSP-4) to adult rats causes widespread degeneration of locus
      coeruleus (LC) axon terminals. The present study was conducted to determine the
      effects of DSP-4-induced LC axon lesions on LC cell bodies. Six months after DSP
      4 treatment, quantitative analysis of Nissl-stained sections revealed a profound
      loss of LC perikarya, ranging from 20 to 73% of control. The remaining LC neurons
      appeared shrunken, but stained strongly with dopamine beta-hydroxylase
      immunohistochemistry. These findings support the conclusion that DSP-4-induced LC
      axon lesions cause retrograde degeneration of LC neurons. DSP-4 may serve as a
      useful tool in studies of the mechanisms of LC neuron degeneration.

PMID- 1984428
TI  - Effects of different sensory and behavioral manipulations on autotomy caused by a
      sciatic lesion in rats.
AB  - We studied the effects of different sensory and behavioral manipulations on
      autotomy (self-mutilation). Lidocaine and bupivacaine pretreatments of the
      transected nerves delayed the onset of autotomy. Short prelesional stimulation
      (crush) of the transected nerve did not enhance autotomy significantly. Daily
      handling decreased autotomy behavior strongly and a visual cue placed on the
      denervated skin increased autotomy slightly. The delayed onset of the autotomy
      behavior after locally administered anesthetics suggests that the lesion-induced
      afferent barrage modified self-mutilation. The decreased self-mutilation after
      daily handling could be a consequence of handling stress. The increase of
      autotomy after the visual cue might have resulted from the attention-induced
      increase of the activity in ascending nociceptive tracts.

PMID- 1984429
TI  - The role of the cingulum bundle in self-mutilation following peripheral
      neurectomy in the rat.
AB  - Peripheral neurectomy in rats is followed by self-mutilation of the denervated
      zone (autotomy), which is assumed to represent an index of pain or dysesthesia
      associated with deafferentation. This study examines the role of the cingulum
      bundle in mediating autotomy behavior. Rats were given bilateral injections of 1
      microliter of 0.5% bupivicaine (a local anesthetic) or saline into the cingulum
      bundle immediately prior to, and on Days 1, 7, 14, and 21 after, sectioning the
      sciatic and saphenous nerves. Bupivicaine injections into the cingulum produced a
      significant delay in the onset of self-mutilation and reduced the overall degree
      of autotomy. Furthermore, the delayed onset of autotomy exceeded the duration of
      the anesthetic block produced by bupivicaine.

PMID- 1984430
TI  - Decussation of bulbospinal respiratory axons at the level of the phrenic nuclei
      in adult rats: a possible substrate for the crossed phrenic phenomenon.
AB  - The axonal trajectories of inspiratory bulbospinal neurons were examined after
      deposition of the anterograde neuronal tracer phaseolus vulgaris leucoagglutinin
      (PHA-L) into the rostral ventral respiratory group in rats. At the level of the
      phrenic nucleus, PHA-L-labeled bulbospinal axons crossed the midline of the
      spinal cord in both the anterior gray and the anterior white commissure. These
      spinally decussating neurons provide a possible anatomical substrate for the
      respiratory reflex known as the crossed phrenic phenomenon.

PMID- 1984431
TI  - Effect of chronic adrenalectomy on neuron loss and distribution of sulfated
      glycoprotein-2 in the dentate gyrus of prepubertal rats.
AB  - This study extends the unexpected finding of Sloviter et al. (Science, 1989, 243:
      535-538) that adrenalectomy (ADX) of young rats casues a loss of granule neurons
      in the dentate gyrus. In particular, we determined how the vulnerability of
      dentate granule neurons to the cytocidal effect of ADX is related to the
      completeness of the ADX and whether sulfated glycoprotein-2, a putative component
      of programmed cell death, is associated with the death of granule neurons after
      ADX. We report that 4 months after bilateral ADX of young (150-175 g) rats only
      ADX rats that had attenuated weight gain and less than 2 ng/ml of serum
      corticosterone lost granule neurons; whereas as little as 15 ng/ml of serum
      corticosterone was sufficient to protect granule neurons from cell death. In
      addition, by immunocytochemistry, SGP-2 was distributed as punctate deposits
      throughout the molecular layer of the dentate gyrus and in glial cells juxtaposed
      to surviving neurons in the dentate of ADX rats with a granule cell loss.
      However, immunoreactivity for SGP-2 was not found in granule neurons that
      exhibited morphological signs of cellular generation after ADX.

PMID- 1984432
TI  - Host regulation of noradrenaline release from grafts of seizure-suppressant locus
      coeruleus neurons.
AB  - Intrahippocampal implants of noradrenaline-rich neural tissue from the fetal
      locus coeruleus region suppress development of seizures induced by hippocampal
      kindling stimulation in hyperexcitable, noradrenaline-depleted rats. In the
      present study the intracerebral microdialysis technique has been used to monitor
      seizure-induced release of noradrenaline from such grafts. The steady-state
      output of noradrenaline in the hippocampus of grafted animals (previously treated
      with intraventricular 6-hydroxydopamine) was similar to the baseline level in
      normal rats. A generalized seizure gave rise to a threefold increase of
      hippocampal noradrenaline levels as compared to baseline (15-min samples) in both
      normal and grafted animals. The maximal increase of extracellular noradrenaline
      levels occurred within 2-4 min after the onset of seizure activity and the levels
      then tapered off, reaching baseline after another 6-8 min. In 6-hydroxydopamine
      treated animals without grafts baseline noradrenaline levels were markedly
      reduced compared to those of normal rats and only minor changes were observed in
      response to seizures. This supports the theory that the high extracellular
      noradrenaline concentrations measured in conjunction with seizures originate from
      the grafts. A knife cut transecting the ascending bundle from the locus coeruleus
      led to a marked attenuation of the seizure-induced increase of noradrenaline
      release in normal animals. In the intact brain, and probably also in the grafts,
      this response thus seems to be dependent on impulse flow in locus coeruleus
      neurons and only to a minor extent on local regulatory mechanisms in the
      hippocampus. In conclusion, the present study demonstrates that grafted locus
      coeruleus neurons are able to restore both basal and seizure-induced
      extracellular noradrenaline levels in the hippocampus.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1984433
TI  - Estradiol replacement to female rats facilitates dorsal hippocampal but not
      ventral hippocampal kindled seizure acquisition.
AB  - Estradiol replacement facilitates amygdala and neocortical kindling. This study
      determined if estradiol also interacts with kindling of additional limbic sites,
      the dorsal (dH) and ventral (vH) hippocampus. During dH stimulations,
      ovariectomized female rats with estradiol (E) replacement required 29.7 +/- 3.5
      trials to kindle and accumulated 1170 +/- 90 s of afterdischarge (AD),
      significantly less than the 40.6 +/- 3.7 trials and 1620 +/- 225 s in rats
      without estradiol (nE). E did not significantly alter the long series of partial
      limbic seizures preceding generalized seizures despite the early appearance of AD
      in the contralateral amygdala. E significantly advanced the onset of generalized
      seizures compared to nE (22.7 +/- 2.3 versus 27.9 +/- 3.2 trials), an event
      coincident with neocortical AD development. Following secondary seizure
      generalization, E rats rapidly completed late-kindled seizure acquisition. In
      contrast, nE rats required an almost twofold greater number of AD trials and AD s
      to complete late kindling compared to E rats. One factor in the slower late
      kindling of nE rats was the instability of generalized seizures which frequently
      regressed to focal or partial responses. In marked contrast to dH kindling, vH
      kindling was uneffected by E replacement. The results provide further
      experimental evidence for a role for estradiol in catamenial epilepsy and support
      our previous work suggesting that the focal origin of seizure development is
      critical to E facilitation of kindling and that secondary generalization of
      seizures is especially sensitive to estradiol.

PMID- 1984434
TI  - Adult rat retinal glia in vitro: effects of in vivo crush-activation on glia
      proliferation and permissiveness for regenerating retinal ganglion cell axons.
AB  - The effects of optic nerve crush on adult rat retinal glia activation were
      studied in vitro. In adult rats the optic nerves were crushed and the
      corresponding retinae were explained 5 to 7 days later and cultured in vitro. The
      glial response of retinae with precrushed optic nerves was compared to the glial
      response of retinae without prior optic nerve crush. As a consequence of crush
      axotomy more glial cells migrated out from retinal explants and covered
      significantly larger areas of the substratum than glia from noncrushed retinae.
      Migration of immunohistochemically distinguishable Vimentin-positive Muller cells
      and glial fibrillary acidic protein-positive astrocytes could be observed in both
      types of cultures. Astrocytes as well as Muller cells incorporated
      bromodeoxyuridine after explantation. In noncrushed retinal explants Thy 1.1
      immunopositive flat cells were much more frequent and the relative proportion of
      glial cells was much lower than in crush-activated cultures. In a second set of
      experiments the ability of adult rat retinal glia to support retinal ganglion
      cell regeneration was examined. Normal retinal explants (without optic nerve
      crush) which usually do not substantially regenerate axons were cultured on
      retinal glia from normal and crush-activated explants. Both glia preparations
      supported axon growth from retinal explants after 3 days in vitro. Neuritic
      growth was significantly better when retinal explants from normal adult rats were
      cultured on crush-activated retinal glia as compared to glia derived from
      noncrushed retinae. It is concluded that activated adult rat retinal glia, unlike
      adult glia found in other brain regions, support adult rat retinal ganglion cell
      regeneration in vitro.

PMID- 1984435
TI  - Astrocyte hypertrophy in the dentate gyrus of young male rats reflects variation
      of individual stress rather than group environmental complexity manipulations.
AB  - Glial hypertrophy is associated with synaptogenesis in visual cortex and with
      stress-induced damage in the hippocampus. This study examined astrocytes in the
      dentate gyrus of male weanling rats exposed to complex or standard laboratory
      environments. No group differences in astrocytic surface density were observed,
      as expected in this brain region where group differences in synaptogenesis in
      male rats are reportedly minimal. Similarly, no group differences in adrenal
      weight were observed. Across all treatment groups, however, a significant
      positive correlation (r = 0.57) between adrenal weight and surface density of
      astrocytic processes was found. Considerable variation in responses of individual
      rats to their environments occurs in both the complex and the laboratory cage
      environments, and animals responding poorly may have had heavier adrenals and
      greater astrocyte reactivity in the dentate gyrus. Thus astrocyte hypertrophy in
      the dentate gyrus reflects the stress history of the individual rat and not any
      differential effects of rearing in a complex or a laboratory cage environment.

PMID- 1984436
TI  - Quantitative cytoarchitectural analysis of cellular degeneration in the dorsal
      lateral geniculate nuclei of cats and kittens with cerebral hemispherectomy.
AB  - Quantitative morphometry was used to study the effects of maturationally
      dependent responses to brain trauma on the cytologic organization of the dorsal
      lateral geniculate nucleus (LGd). The left hemitelencephalon was removed in adult
      cats and in neonatal kittens and resultant changes in cell size and density were
      compared between these groups and with intact controls. Morphological changes
      were found bilaterally in all lesioned cats. Ipsilaterally, geniculate volume was
      reduced by 23% in kitten-lesioned cats and by 33% in adult-lesioned cats. The
      geniculate of both lesion groups contained fewer neurons in all laminae than did
      the nucleus of intact cats, but only the adult-lesioned cats showed a substantial
      increase in glial cell counts. Contralaterally, there was a tendency for a lower
      neuronal density in both lesion groups, but this was significant only for the A
      laminae of adult-lesioned cats. Therefore, neonatal lesions spared more neurons
      bilaterally and produced minimal ipsilateral gliosis compared to the adult
      ablation. Results are discussed within the context of the "Gudden effect" which
      asserts that there is more retrograde degeneration in neonatal versus adult brain
      lesioned animals.

PMID- 1984437
TI  - Compensatory sprouting of uninjured magnocellular neurosecretory axons in the rat
      neural lobe following unilateral hypothalamic lesion.
AB  - Axonal sprouting of intact neurons of the magnocellular neurosecretory system was
      investigated using a unilateral hypothalamic knife cut of the
      hypothalamoneurohypophysial tract to partially denervate the rat neural lobe
      (NL). Densitometric, morphometric, ultrastructural, and metabolic measures were
      utilized to demonstrate the compensatory response to denervation in this system.
      Densitometric analysis revealed a transient reduction in the intensity of
      vasopressin staining in the NL at 10 days postsurgery (PS) with a subsequent
      recovery by 20 days PS. There was a comparable initial reduction in the cross
      sectional area of the NL followed by a more gradual recovery to normal by 90 days
      PS. Ultrastructural investigation revealed a reduction in total axon number in
      the NL at 10 days PS similar to the declines in vasopressin immunoreactivity and
      size of the NL. A subsequent partial recovery of axon number occurred,
      paralleling the return to normal NL size between 30 and 90 days PS. Hypertrophy
      of both somata and cell nuclei of magnocellular neurons in the supraoptic and
      paraventricular hypothalamic nuclei contralateral to the lesion was also apparent
      during this period. Daily measurements of urine osmolality revealed an initial
      transient hypoosmolality followed by a chronic hyperosmolality which persisted
      throughout the 90 day postsurgical period. There was a concomitant chronic
      decrease in both daily drinking and urine excretion volumes which began
      immediately following surgery. These results suggest that intact, contralateral
      magnocellular vasopressinergic efferents undergo compensatory sprouting as a
      result of partial denervation of the NL in the absence of a functional deficit in
      vasopressin.

PMID- 1984438
TI  - Surfactant-potentiated increases in intracranial pressure in a mouse model of
      Reye's syndrome.
AB  - Severe encephalopathy, the usual cause of death in Reye's syndrome (RS), is
      characterized by cerebral edema with associated increases in intracranial
      pressure (ICP). In previous studies, we have shown that exposure of neonatal mice
      to nontoxic doses of an industrial surfactant and subsequent infection with mouse
      adapted influenza B (Lee) virus result in a significant increase in mortality
      rate and that this is associated with several of the characteristic features of
      human RS. In the present study we have measured ICP in the young mice undergoing
      their version of the disease, and we now report that the animals treated with
      surfactant plus virus experience increases in intracranial pressure that are
      significantly in excess of those in any of the three control groups. These
      findings support our hypothesis that this and the other abnormal biochemical and
      morphological responses in RS are related in some manner to a chemically
      compromised host.

PMID- 1984439
TI  - Effects of infant versus adult pyramidal tract lesions on locomotor behavior in
      hamsters.
AB  - The role of the pyramidal tract in locomotion was studied in hamsters by
      analyzing their locomotor behavior after lesions of the medullary pyramidal
      tract. Animals with lesions either as adults or as infants were compared to
      determine whether early pyramidotomy results in greater functional recovery.
      Normal and pyramidotomized animals were filmed during locomotion on a runway
      consisting of either smooth or rough terrain to assess whether the uneven surface
      would accentuate locomotor deficits. Frame-by-frame analysis of the filmed
      behavior during all phases of the step cycle was carried out to determine
      positions of the joints of the forelimb and hindlimb during locomotion. Accuracy
      of limb placement on the rough terrain was determined by observations of
      consecutive step cycles. The results show that lesions of the pyramidal tract in
      both infant and adult hamsters affect locomotion first by causing a reduction in
      the yielding phase of the step cycle and second by producing inaccuracies of
      forelimb placement. Rough terrain accentuates deficits in forelimb placement
      during locomotion. Animals with lesions as infants and those with lesions as
      adults show surprisingly similar deficits in locomotion, with the exception that
      animals with lesions as infants show some behavioral compensation in hindlimb
      movement by developing a normal degree of yielding at the knee. In contrast,
      hamsters with lesions as either adults or infants never recover normal forelimb
      behavior in either yielding at the elbow or accuracy of forelimb placement. These
      results emphasize the sensorimotor role of the pyramidal tract, even in a
      relatively stereotyped behavior such as locomotion.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1984440
TI  - The specificity of anti-DNA antibodies in systemic lupus erythematosus.

PMID- 1984441
TI  - IL-6 and IL-1 enhance the accessory activity of human blood monocytes during
      differentiation to macrophages.
AB  - The role of IL-6 and IL-1 in the regulation of accessory activity and
      differentiation in the human monocyte/macrophage (Mo/Mph) system was
      investigated. IL-6 combined with IL-1 had a strong effect on the accessory
      activity of Mo-derived cells dependent on their state of differentiation in
      vitro. Fresh Mo prepared from peripheral blood differentiated into potent
      accessory cells in vitro within 24 h in the absence of exogenous triggers in
      serum-containing and serum-free medium. Mo cultured for 2 days in the presence of
      the cytokines IL-6 and IL-1 did not significantly increase their spontaneous
      accessory activity. However, the simultaneous addition of antibodies against IL-6
      and IL-1 to accessory Mo cultures significantly diminished their T cell
      stimulatory capacity. These findings suggest an important positive feedback role
      of IL-6 and IL-1, secreted by Mo at this early state of differentiation. In
      marked contrast, untreated mature Mph generated in vitro from Mo exhibited a low
      spontaneous accessory potency. However, when these cells were subjected to IL-6
      and/or IL-1, we observed a strong dose dependent increase in their potency to
      stimulate a T cell response. Parameters indicating the differentiation of Mo to
      Mph, such as acid phosphatase and 5' nucleotidase, were not influenced by the
      addition of IL-1, IL-6, or a mixture of both and confirmed the presence of mature
      Mph after 6 days of culture. Based on these observations, we conclude that the
      monocyte-derived cytokines IL-6 and IL-1 not only directly act on T cells but may
      also function as a signal for accessory activity during Mo/Mph differentiation.

PMID- 1984442
TI  - Differences in the tumor necrosis factor-alpha-mediated lysis by fixed natural
      cytotoxic cells and fixed cytotoxic macrophages.
AB  - TNF-alpha has been shown to be associated with macrophage cell membranes in such
      a way as to retain cytolytic activity despite fixation of the macrophage effector
      cells with paraformaldehyde. In this paper we report that, similar to cytotoxic
      macrophages, natural cytotoxic (NC) cells also use cell-associated TNF to lyse
      sensitive target cells. However, in contrast to fixed cytotoxic macrophages, NC
      cells do not retain cytolytic activity after fixation with paraformaldehyde.
      Additionally, the cytolytic activity of paraformaldehyde-fixed NC cells is not
      increased by incubation with LPS or by incubation with rTNF before fixation.
      Western blot analysis indicates that, unlike macrophages, NC cells use a smaller
      (17 kDa) constitutively active form of TNF. These results indicate that, although
      both macrophages and NC cells use effector cell-associated TNF to mediate lysis
      of sensitive targets, the way in which TNF is associated with these two types of
      effector cells must be different.

PMID- 1984443
TI  - Enhanced in vivo targeting of an asymmetric bivalent hapten to double-antigen
      positive mouse B cells with monoclonal antibody conjugate cocktails.
AB  - In order to target specifically double-Ag-positive cells in vivo, we synthesized
      chemically two mAb conjugates with specificities for both an allelic murine B
      cell-surface Ag and for a synthetic hapten. One conjugate was designed for its
      specificities for I-Ek and for N-epsilon-(2,4-DNP)-amino-caproate, and the other
      one for its reactivity to Lyb-8.2 and to indium-diethylenetriamine pentaacetate.
      A radiolabeled tracer, containing both the N-epsilon-(2,4-DNP)-amino-caproate and
      the indium-diethylenetriamine pentaacetate haptens, was obtained by reacting
      diethylenetriamine pentaacetic acid dianhydride with mono-[N-epsilon-(2,4-DNP)
      amino-caproyl]-tyrosyl-lysine and labeling with indium-111. Mice from various
      strains (CBA/N: I-Ek+, Lyb-8.2+; AKR/N: I-Ek+, Lyb-8.2-; BALB/c: I-Ek-, Lyb-8.2+;
      and DBA/2: I-Ek-, Lyb-8.2-) were given simultaneous i.v. injections of microgram
      amounts of less than anti-[N-epsilon-(2,4-DNP)-amino-caproate], anti-I-Ek greater
      than and of [anti-(indium-diethylene-triaminepentaacetate), anti-Lyb-8.2]
      antibody conjugates and picomole amounts of the tracer. As expected, specific
      uptake of the tracer by the spleen was observed in strains where spleen cells
      expressed at least one Ag (CBA/N, AKR/N, and BALB/c). Furthermore, spleen cells
      from the double-Ag-positive mouse strain (CBA/N), when compared with spleen cells
      from single-positive mouse strains, exhibited a significantly higher uptake of
      the bivalent hapten. This specificity for double-Ag-positive cells, it is
      suggested, occurs through the formation of stable complexes between both cell
      surface Ag, both conjugates, and the asymmetric bivalent hapten. The use of such
      asymmetric bivalent haptens, together with matched (anti-hapten, anti-cell)
      antibody conjugates, is proposed as a general method for increasing the in vivo
      specificity of immunoimaging and radioimmunotherapy.

PMID- 1984444
TI  - Polyclonal activation of the murine immune system by an antibody to IgD. XI.
      Contribution of membrane IgD cross-linking to the generation of an in vivo
      polyclonal antibody response.
AB  - The injection of mice with a foreign, polyclonal antibody to IgD sequentially
      induces: 1) activation of B cells by cross-linking of their cell membrane (m)
      IgD; 2) B cell processing and presentation of the bound anti-IgD antibody to T
      cells; 3) activation of these T cells; and 4) T-dependent stimulation of B cell
      differentiation into IgG1 secreting cells. To determine whether the cross-linking
      of B cell membrane IgD and/or the resulting B cell activation that follows
      contribute to the generation of the polyclonal IgG1 response, we examined the
      abilities of three sets of anti-delta mAb or mAb fragments to stimulate
      polyclonal IgG1 production. Within each set mAb were matched for species and Ig
      isotypic determinants, but differed in avidity for IgD or in ability to cross
      link IgD. In addition, experiments were performed to determine whether the anti
      delta mAb had to be foreign to the immunized mouse to stimulate an IgG1 response.
      Results of these experiments indicate that: 1) recognition of the injected anti
      delta antibody as foreign is required for the induction of a polyclonal IgG1
      response; 2) the cross-linking of B cell membrane Ig, which directly activates B
      cells, can contribute considerably to the generation of in vivo IgG1 production;
      and 3) that even relatively weak cross-linking of membrane Ig by ligands that
      bind it with low avidity can make this contribution.

PMID- 1984445
TI  - Production of prostaglandin E2 and prostacyclin by thymic nurse cells in culture.
AB  - To better define the thymic microenvironment, we have examined a specific
      population of thymic stromal cells, thymic nurse cells (TNC) for production of
      eicosanoids. TNC were prepared from BALB/c mice, cultured in complete medium, and
      culture supernatants were analyzed for the presence of various metabolites of
      arachidonic acid. Freshly isolated TNC produced large quantities of PGE2 and 6
      keto PGF1 alpha (a stable metabolite of prostacyclin, PGI2). Both of these
      eicosanoids were produced continuously in culture, after an initial lag period of
      approximately 2 h. No significant production of the eicosanoids PGD2, thromboxane
      B2, or leukotrienes B4, C4/D4/E4 was seen in these cultures. Production of PGE2
      and PGI2 by TNC was not stimulated by treatment with the calcium ionophore
      A23187, or by cell-cell interactions resulting from coculture of the TNC with
      free thymocytes. Eicosanoid production in these cultures was not due to
      production of these substances by cells likely to be present as contaminants,
      such as T rosettes or free thymocytes. These findings raise the possibility that
      PGE2 and/or PGI2 may provide signals to thymocytes at a specific developmental
      stage.

PMID- 1984446
TI  - Moderate zinc deficiency in rhesus monkeys. An intrinsic defect of neutrophil
      chemotaxis corrected by zinc repletion.
AB  - Experimental animals fed zinc-deficient diets are well known for susceptibility
      to infections and impaired mitogen response and Ig production. However, the
      levels of zinc deficiency used have generally been severe, not comparable to
      human populations, and have not addressed neutrophil function. To address this
      issue we have studied the effect in rhesus monkeys of a well defined moderately
      zinc-deficient (MZ) diet on polymorphonuclear leukocyte (PMN) function. Female
      adult rhesus monkeys were fed either a control (100 micrograms Zn/g) or MZ (2
      micrograms Zn/g) diet for 9 mo with quantitation of PMN chemotaxis, and
      phagocytosis of opsonized yeast. In addition, membrane potential and secretion
      responses (changes in 90 degrees light scatter) and changes in PMN shape (forward
      light scatter shifts) were also measured. When compared to the PMN of animals fed
      control diets, there was a significant reduction in chemotaxis to FMLP of MZ-fed
      monkey PMN. Although shape change, cell membrane depolarization, as well as
      phagocytosis were not significantly different among the two groups, the PMN of MZ
      animals had significantly lower relative loss of orthogonal light scatter
      (degranulation) due primarily to a lower resting orthogonal light scatter and
      also a smaller loss when stimulated with FMLP. In vitro addition of zinc to the
      cells (25 microM) did not improve chemotaxis, and in fact, was inhibitory for
      most control and zinc-deficient cells. However, after 2 wk of dietary zinc
      repletion (100 micrograms Zn/g), chemotaxis in the low zinc group was higher and
      comparable to the control response. These data indicate that zinc deficiency is
      associated with an intrinsic PMN defect that specifically affects chemotaxis and
      is corrected with dietary zinc repletion.

PMID- 1984447
TI  - Immunogenicity and protective effect against oral colonization by Streptococcus
      mutans of synthetic peptides of a streptococcal surface protein antigen.
AB  - Streptococcus mutans is known to be a major causative organism of human dental
      caries. A surface protein Ag with a molecular mass of 190 kDa of S. mutans (PAc)
      is receiving attention as an anticaries vaccine. We have recently determined the
      complete nucleotide sequence of the gene for PAc. In this study, four peptides
      were synthesized on the basis of amino acid sequence of PAc. Among these
      peptides, PAc(301-319) corresponding to the alanine-rich repeating amino acid
      region was the most strongly bound by polyclonal murine anti-rPAc antibodies. The
      peptide partially inhibited the binding of polyclonal anti-rPAc antibodies to
      rPAc. The peptide induced the proliferation of T cells from BALB/c mice immunized
      with rPAc. Subcutaneous immunization with PAc(301-319) or rPAc emulsified in
      CFA/IFA induced high serum IgG responses to rPAc and PAc(301-319). In addition,
      serum IgG responses to a surface protein Ag with a molecular mass of 210 kDa of
      Streptococcus sobrinus were elicited in mice immunized by s.c. injection with
      PAc(301-319) or rPAc. Intranasal immunization with PAc(301-319) coupled to
      cholera toxin B subunit (CTB) or with rPAc and free CTB induced high serum IgG
      responses to rPAc. The immunization with PAc(301-319) coupled to CTB or rPAc and
      free CTB suppressed the colonization of murine teeth by S. mutans. These results
      suggest that intranasal immunization with the peptide or rPAc may be effective
      for the prevention of dental caries.

PMID- 1984449
TI  - Induction of NF-KB during monocyte differentiation by HIV type 1 infection.
AB  - The production of human immunodeficiency virus type 1 (HIV-1) progeny was
      followed in the U937 promonocytic cell line after stimulation either with
      retinoic acid or PMA, and in purified human monocytes and macrophages.
      Electrophoretic mobility shift assays and Southwestern blotting experiments were
      used to detect the binding of cellular transactivation factor NF-KB to the double
      repeat-KB enhancer sequence located in the long terminal repeat. PMA treatment,
      and not retinoic acid treatment of the U937 cells acts in inducing NF-KB
      expression in the nuclei. In nuclear extracts from monocytes or macrophages,
      induction of NF-KB occurred only if the cells were previously infected with HIV
      1. When U937 cells were infected with HIV-1, no induction of NF-KB factor was
      detected, whereas high level of progeny virions was produced, suggesting that
      this factor was not required for viral replication. These results indicate that
      in monocytic cell lineage, HIV-1 could mimic some differentiation/activation
      stimuli allowing nuclear NF-KB expression.

PMID- 1984448
TI  - Complete cDNA sequence of human complement pro-C5. Evidence of truncated
      transcripts derived from a single copy gene.
AB  - Two truncated human C5 clones, pHC5A and pHC5B, were isolated from an adult human
      liver cDNA library, and contained inserts of 2930 and 2181 bp, respectively. Both
      clones were polyadenylated and encoded the 5'-end of the C5 pro-molecule, thereby
      completing the human pro-C5 cDNA sequence. However, near the 3'-ends, at
      exon/intron boundaries, the nucleotide sequences of pHC5A and pHC5B diverged from
      each other and from the full-length 6.0-kb C5 cDNA sequence. Clone pHC5A, which
      overlapped the first human C5 clone described (J-16), encoded most of the C5
      signal peptide, the complete beta-chain, the linker peptide, 177 amino acids of
      the alpha-chain, and contained 144 bp of Alu family consensus sequence encoding
      48 amino acids of divergent protein sequence in an open reading frame. Clone
      pHC5B encoded the entire C5 signal peptide, the beta-chain, the linker peptide,
      nine amino acids of the alpha-chain, and six amino acids of divergent protein
      sequence in an open reading frame. Northern blot experiments demonstrated the
      presence of a 3.0-kb truncated C5 mRNA in adult human liver and a 4.8-kb
      truncated C5 mRNA in HepG2 cells in addition to the 6.0-kb full-length
      transcript. Truncated C5 mRNA were not detected in Raji, MOLT-4, human fibroblast
      or U937 cells, although the full-length 6.0-kb transcript was seen in MOLT-4
      cells. Southern blot analyses indicated that the human C5 structural gene is
      large, complex, and is present in the human genome in a single copy, thereby
      demonstrating that the truncated C5 clones and mRNA are derived from a single C5
      gene by alternative processing events.

PMID- 1984450
TI  - Cytolytic lymphocytes induce both apoptosis and necrosis in target cells.
AB  - We examined the role of programmed cell death (apoptosis) in killer lymphocyte
      mediated cytotoxicity. Two parameters of cell death, 51Cr release and DNA
      fragmentation, were assayed. Lymphokine-activated killer cell- or CTL-mediated
      death was inhibited in target cells where transcription or translation were
      blocked. Dying target cells showed ultrastructural changes typically associated
      with both apoptosis and necrosis. In contrast, target cells pretreated with
      macromolecular synthesis inhibitors and incubated with lymphokine-activated
      killer cells showed morphologic signs of necrosis only. Zn2+, an inhibitor of
      endonucleases, inhibited DNA fragmentation, but not 51Cr release in YAC-1 target
      cells, suggesting that the two effects can be dissociated. Finally, the cytotoxic
      effect of perforin, a pore-forming protein of killer lymphocytes that is known to
      cause necrotic death, was unaffected by the inhibition of either RNA or protein
      synthesis in target cells. Taken together, these results suggest that killer
      lymphocytes can induce both necrosis and apoptosis and that the two types of
      death can be dissociated with specific inhibitors.

PMID- 1984451
TI  - Antigen-induced Ca2+ signaling and desensitization in B cells.

PMID- 1984452
TI  - B cell activation during HIV-1 infection. II. Cell-to-cell interactions and
      cytokine requirement.
AB  - This study examined the mechanisms underlying the intense activation of HIV-1
      specific B cells observed in peripheral blood of HIV-1-infected subjects.
      Spontaneous in vitro synthesis of anti-HIV-1 antibodies, as well as total Ig
      production, were dramatically reduced by accessory cell, but not T cell removal.
      This fall was counteracted by addition of rIL-6, but not other cytokines, to
      monocyte-depleted cultures; moreover, antisera against IL-6 suppressed
      spontaneous anti-HIV-1 antibody synthesis in a dose-dependent manner. Although IL
      6 apparently sustained HIV-1-specific B cell activation, no increase in serum IL
      6 levels was observed; PBMC from seropositive subjects did not produce increased
      amounts of IL-6 in vitro, compared to seronegative controls, both spontaneously
      and in the presence of LPS stimulation; finally, no constitutive expression of IL
      6 gene could be documented in freshly isolated PBMC. These findings indicate that
      IL-6 may play a central role in HIV-1-specific B cell activation in seropositive
      patients, and further stress the importance of this cytokine during HIV-1
      infection.

PMID- 1984453
TI  - The molecular configuration and ultrastructural locations of an IgG Fc binding
      site in human colonic epithelium.
AB  - Previously, we discovered a binding site for the Fc region of IgG in human small
      intestinal and colonic mucosa. The binding site (Fc gamma IBS) appeared to be
      primarily associated with goblet cells, to consist of greater than 200,000 Da and
      78,000 Da components, and to be distinct from leukocyte FcR. In the present work,
      we used mAb made to colonocyte IgG-binding material to more accurately define the
      molecular structure and cellular locations of the Fc gamma IBS. In immunoblot and
      fast protein liquid chromatography analysis, the mAb revealed that the Fc gamma
      IBS consists of a 110,000- to 140,000-Da component in addition to the two
      components previously recognized. The greater than 200,000 component may be the
      critical component for IgG binding, inasmuch as mAb to it but not to the other
      two components inhibited binding of IgG to colonic sections in vitro. Used in
      immunoelectron microscopy, the mAb documented that the Fc gamma IBS is present in
      the endoplasmic reticulum of goblet cells, in the cytoplasmic matrix separating
      secretory granules of goblet cells, and within the granules themselves;
      occasionally it has the appearance of being secreted into the intestinal lumen
      with mucus. The Fc gamma IBS could not be solubilized from colonocyte homogenates
      by three different detergents, which suggests that it exists in complex with
      cytoskeletal elements. We speculate that the Fc gamma IBS aids in immunologic
      protection of the intestine by facilitating interaction between intestinal mucus
      and antigenic material in the lumen.

PMID- 1984454
TI  - Cocaine potentiates HIV-1 replication in human peripheral blood mononuclear cell
      cocultures. Involvement of transforming growth factor-beta.
AB  - Cocaine use is an important high risk behavior in the AIDS epidemic. In this
      study, we tested the hypothesis that cocaine potentiates the replication of HIV-1
      in human PBMC. A coculture system was used in which PBMC from healthy donors were
      incubated in the absence (control) or presence of cocaine before activation with
      PHA. Cocultures were then constituted with PBMC infected with a clinical isolate
      of HIV-1. HIV-1 replication, which was assessed by the measurement of HIV-1 p24
      antigen levels in coculture supernatants, was significantly increased in a dose
      dependent manner by cocaine with maximal stimulation at a concentration of 10(-9)
      M (965 +/- 196 vs 303 +/- 80 pg p24 Ag/ml in control cocultures). Antibodies to
      transforming growth factor-beta (TGF-beta) blocked cocaine-enhanced HIV-1
      replication and purified TGF-beta stimulated viral replication in a manner
      similar to that observed with cocaine. Augmentation of HIV-1 replication by TGF
      beta was maximal at a concentration of 0.01 ng/ml; however, viral proliferation
      appeared to be inhibited by concentrations of TGF-beta of 1 ng/ml or greater.
      Taken together, these results indicate that cocaine augments the replication of
      HIV-1 in PHA-activated PBMC via a mechanism that appears to involve TGF-beta.

PMID- 1984456
TI  - Pneumococcal pneumonia in a rat model of cirrhosis: effects of cirrhosis on
      pulmonary defense mechanisms against Streptococcus pneumoniae.
AB  - To study alterations in host defense mechanisms that enhance pneumococcal
      virulence, a model of Streptococcus pneumoniae pneumonia was developed in
      cirrhotic rats. Cirrhosis, with or without ascites, was produced in rats by
      intragastric administration of carbon tetrachloride (CCl4). Histopathologic and
      laboratory studies demonstrated that CCl4-induced cirrhosis was similar to
      alcoholic cirrhosis in humans. Cirrhotic rats were more susceptible to type 3
      pneumococcal pneumonia induced by intratracheal challenge than controls, and the
      presence of ascites was associated with the lowest LD50. More cirrhotic rats with
      ascites had bacteremia and elevated levels of circulating capsular antigen after
      challenge compared with cirrhotic rats without ascites or controls. Pulmonary
      clearance of pneumococci was markedly reduced in rats with cirrhosis and ascites
      and was associated with reduced serum complement levels. This model may be useful
      in further studies of the pathogenesis and therapy of pneumococcal infections in
      the compromised host.

PMID- 1984455
TI  - Evidence for the targeting by 2-oxo-dehydrogenase enzymes in the T cell response
      of primary biliary cirrhosis.
AB  - Primary biliary cirrhosis (PBC) is a chronic autoimmune liver disease that
      includes the presence of lymphoid infiltrates in portal tracts, high titer
      autoantibodies against pyruvate dehydrogenase-E2 (PDH-E2) and branched chain
      ketoacid dehydrogenase-E2 (BCKD-E2), and biliary tract destruction. The mechanism
      by which the autoimmune response is induced, the specificity of damage to the
      biliary epithelium, and the role of T cells in PBC are still unknown. To address
      these issues, we have taken advantage of a mouse mAb, coined C355.1, and studied
      its reactivity against a panel of liver tissue from normal subjects as well as a
      panel of liver specimens from patients with PBC, progressive sclerosing
      cholangitis, and chronic active hepatitis (CAH). C355.1, much like human
      autoantibodies to PDH-E2, reacts exclusively by immunoblotting with PDH-E2, binds
      to the inner lipoyl domain of the protein, and inhibits PDH-E2 activity in vitro.
      In addition, we have also attempted to develop cloned T cell lines that react
      with PDH-E2 and/or BCKD-E2 using liver biopsies from patients with PBC, compared
      with CAH. Although monoclonal C355.1 produced typical mitochondrial fluorescence
      on sections of normal liver, pancreas, lung, heart, thyroid, and kidney, it
      produced a distinct and intense reactivity when used to stain the bile ducts of
      patients with PBC. Nine of 13 PBC liver biopsies studied herein contained bile
      ducts on light microscopy, all of which reacted intensely at a 1:100 culture
      supernatant dilution of monoclonal C355.1. In contrast, although bile ducts of
      liver specimens from normals, CAH, and progressive sclerosing cholangitis also
      reacted with C355.1, such reactivity was exclusively mitochondrial and readily
      detectable only at a dilution of 1:2. More importantly, we generated CD4+, CD8-,
      alpha beta TCR+ cloned T cell lines from patients with PBC, but not from CAH,
      that produced IL-2 specifically in response to PDH-E2 or BCKD-E2.

PMID- 1984457
TI  - The human antibody response to streptococcal C5a peptidase.
AB  - An ELISA was developed to measure antibody, both IgG and IgA, against the
      streptococcal C5a peptidase (SCP), in human sera and saliva. Generally, sera and
      saliva from young, uninfected children lacked antibody to SCP. In contrast, most
      sera and saliva specimens from healthy adults had measurable levels of anti-SCP
      IgG and SCP-specific secretory IgA (anti-SCP sIgA). Paired acute and convalescent
      sera from patients with streptococcal pharyngitis possessed significantly higher
      levels of anti-SCP IgG than did sera from healthy individuals. Sera containing
      high concentrations of anti-SCP immunoglobulin were capable of neutralizing SCP
      activity. A survey of healthy adults and children also showed that the latter
      were significantly less likely to have anti-SCP sIgA in their saliva. Detection
      of this antibody in greater than 90% of the saliva specimens obtained from
      children who had recently experienced streptococcal pharyngitis demonstrated that
      children can produce a secretory response. This is thought to be the first report
      of a secretory IgA response in humans to a somatic antigen of Streptococcus
      pyogenes.

PMID- 1984458
TI  - Mediastinitis following coronary artery bypass surgery: a 3-year review.
AB  - Twenty cases of mediastinitis after coronary artery bypass graft operations in
      1985-1987 were reviewed to determine risk factors. Two distinct clusters with a
      methicillin-resistant Staphylococcus aureus (MRSA) strain occurred in 1986. One
      resident was exposed to six cases but to only 5 of 24 controls (P less than
      .008). Cultures of his nares in January and November 1986 revealed the same MRSA
      strain as that of the cases. An attempt to eradicate the resident's nasal
      carriage of MRSA in January 1986 failed; eradication of his carrier state was
      achieved only after treatment with mupirocin. In a case-control study examining
      patients exposed to the resident, a prolonged duration of surgery (P less than
      .05) and a preoperative albumin level of less than 3.0 g/dl (P less than .009)
      were associated with mediastinitis with this MRSA. For the other 14 mediastinitis
      patients, who were not exposed to the resident, a preoperative albumin level of
      less than 3.0 g/dl was also a risk factor (8/14 cases vs. 8/43 controls, P less
      than .009). Thus, this study suggests that it is important to follow MRSA
      disseminators and to recognize that preoperative serum albumin levels are a risk
      factor for mediastinitis.

PMID- 1984459
TI  - Measles among the Amish: a comparative study of measles severity in primary and
      secondary cases in households.
AB  - An outbreak of measles among a predominantly unvaccinated and susceptible Amish
      population in Lebanon County, Pennsylvania, offered the opportunity to test the
      hypothesis that secondary cases in households are more severe than primary cases
      because the former have more intense exposure and receive a greater virus
      inoculum. Of 130 measles cases reported between April and June 1988, 119 (92%)
      constituted a study of disease severity. Severity was assessed by determining
      frequency and duration of symptoms, length of any hospitalization, and number of
      days in bed. In a univariate analysis, fewer secondary cases had conjunctivitis
      (relative risk [RR], 0.67; 95% confidence interval [CI], 0.48-0.96) and headache
      (RR, 0.37; CI, 0.15-0.86), but more had earache (RR, 9.69; CI, 1.8-202.9)
      compared with primary cases. Secondary cases had a shorter mean duration of
      coryza (4.0 vs. 5.0 days, Student's t test, P = .08). However, a logistic
      regression model that matched by family and controlled for age and sex indicated
      that there were no significant differences in measles severity among primary and
      secondary cases in households.

PMID- 1984460
TI  - Human serologic response to envelope-associated proteins and adenylate cyclase
      toxin of Bordetella pertussis.
AB  - The human serologic response to several envelope-associated proteins and
      adenylate cyclase toxin of Bordetella pertussis was examined using immunoblot
      techniques. Antigens recognized by sera from individuals with culture-confirmed
      pertussis and by sera from infants immunized with three doses of conventional
      whole-cell pertussis vaccine included a 63,000-Da protein that was shown to be
      antigenically related to a mycobacterial heat-shock protein. A 29,000-Da protein
      reacted with sera from convalescent individuals, whereas a 91,000-Da protein
      reacted with sera from vaccinated individuals. Antibodies to adenylate cyclase
      toxin were common in sera from individuals diagnosed with pertussis. B. pertussis
      lipooligosaccharide was also recognized by antibodies in some of these sera.
      These data suggest that some of these antigens may play a role in immunity to
      pertussis.

PMID- 1984461
TI  - Infectivity of Borrelia burgdorferi correlates with resistance to elimination by
      phagocytic cells.
AB  - The Lyme disease spirochete, Borrelia burgdorferi, causes a disseminated
      infection in vivo, implying resistance to clearance by phagocytic cells. Because
      B. burgdorferi loses its infectivity after in vitro cultivation, the
      relationships between serial passaging of the organism in vitro, its
      susceptibility to elimination by phagocytes, and its infectivity were examined.
      When three different high-passage strains were incubated for 4 h at 37 degrees C
      with peripheral blood mononuclear cells, macrophages, or polymorphonuclear
      neutrophils, 45%-67% of the organisms were eliminated. In contrast, two low
      passage strains were resistant to elimination by phagocytes, and only 5%-6% of
      the organisms were removed after 4 h. All five strains equally stimulated the
      neutrophil oxidative burst, indicating that evasion of phagocytes was not a
      result of avoidance of recognition by these cells. The two low-passage strains
      were infective when injected into mice, whereas the three high-passage ones were
      not. These observations indicate that infectivity of the Lyme disease spirochete
      correlates with resistance to elimination by phagocytic cells.

PMID- 1984462
TI  - A mycobacterial heat-shock protein-responsive gamma delta T cell clone also
      responds to the homologous human heat-shock protein: a possible link between
      infection and autoimmunity.
AB  - Prokaryotic and eukaryotic cells respond to a variety of stress conditions by
      increasing the synthesis of a family of proteins collectively known as heat-shock
      proteins (HSP). One of these, a 65-kDa HSP that is highly conserved in many
      bacteria, is a major target of the immune response to mycobacteria. A gamma delta
      T cell clone from a healthy donor that recognizes not only the 65-kDa
      mycobacterial HSP but also the recombinant human homologue of this HSP protein
      was raised. Like alpha beta T cell clones, which recognize mycobacterial HSP, the
      clone requires antigen-presenting cells for antigen-induced proliferation and can
      also be directly activated via receptor cross-linking through CD3 or the delta
      chain of the gamma delta T cell receptor. These data suggest that the induction
      of a gamma delta T cell response by bacterial antigens could lead to the
      expansion of cells that respond to autologous proteins and, therefore, may result
      in the development of autoimmunity.

PMID- 1984463
TI  - Pharmacokinetics of intravenous pentamidine in patients with normal renal
      function or receiving hemodialysis.
AB  - The pharmacokinetics of intravenous pentamidine were studied in 10 patients with
      normal renal function (group 1), 9 volunteer subjects without Pneumocystis
      carinii pneumonia who were receiving maintenance hemodialysis (group 2), and 5
      patients with normal or mildly abnormal renal function (group 3) after the last
      dose of therapy. The concentration-time data were best represented by a three
      compartment model. The peak plasma concentration, plasma clearance, and
      elimination half-life ranged from 249 +/- 80 to 227 +/- 110 ng/ml, 268 +/- 70 to
      329 +/- 58 l/h, and 29 +/- 25 to 118 +/- 119 h, respectively, in groups 1 and 2.
      In group 1, trough concentration increased progressively (linear regression: y =
      4.4x; r = .91, P = .001) without achieving steady state, and the renal clearance
      to-plasma clearance ratio was 2.1% +/- 0.01%. In group 3, the elimination half
      life after the last dose was 12.0 +/- 2.3 days. The elimination half-life of
      pentamidine was long and accumulation occurred with daily dosing even in patients
      with normal renal function. Dose adjustment is not recommended for renal
      impairment as renal clearance accounts for a small fraction (2.1%) of plasma
      clearance.

PMID- 1984464
TI  - Use of brain biopsy for diagnostic evaluation of patients with suspected herpes
      simplex encephalitis: a statistical model and its clinical implications. NIAID
      Collaborative Antiviral Study Group.
AB  - Using the decision analysis technique and multivariate regression methods, a
      statistical model was established to define the utility of brain biopsy for
      diagnostic evaluation of patients with suspected herpes simplex encephalitis
      (HSE). Two strategies were compared: strategy I, brain biopsy with acyclovir
      (ACV) treatment for 10 days in biopsy-positive patients, and strategy II, ACV
      therapy without brain biopsy. Strategy I resulted in a greater 6-month survival
      rate when the likelihood of patients having HSE was less than 70%. Based on the
      current estimated prevalence of HSE (for patients with suspected HSE) of 35%,
      strategy I showed a slight advantage of a 3.2% increase in 6-month survival rate.
      An individual patient's chance of a positive brain biopsy can be predicted using
      a mathematical equation based on several important clinical assessments. This
      equation in conjunction with the decision analysis is a useful guide for the
      clinical management of patients with regard to brain biopsy.

PMID- 1984465
TI  - Chemorepulsion of trichomonads by products of neutrophil oxidative metabolism.
AB  - To determine whether secreted neutrophil products affect the migration of motile
      microorganisms such as Trichomonas vaginalis, stimulated human neutrophils and
      cell-free oxygen metabolites were used as stimuli in a multiwell filter
      chemotaxis assay using tritiated T. vaginalis. When stimulated neutrophils were
      present on the opposite side of the filter, migration of T. vaginalis into the
      filter was significantly diminished, and this reduction varied with the dose of
      neutrophil stimulus. The reduction of movement was abrogated by the addition of
      catalase and superoxide dismutase to scavenge oxygen metabolites. Studies with
      cell-free hydrogen peroxide or hypochlorite preparations indicated that the
      reduction in trichomonal trapping in the filter was due to chemorepulsion and not
      to a nonspecific decrease in motility or adherence. These findings suggest that
      active migration away from neutrophil products might be a means by which
      trichomonads avoid the microbicidal functions of host phagocytes.

PMID- 1984466
TI  - Sensitive and specific detection of toxoplasma DNA in an experimental murine
      model: use of Toxoplasma gondii-specific cDNA and the polymerase chain reaction.
AB  - Toxoplasma gondii, an apicomplexan parasite of mammals and birds, is well
      recognized as a cause of encephalitis in AIDS patients and as a cause of
      congenital infections. The polymerase chain reaction (PCR) and toxoplasma cDNA
      clones were used to diagnose T. gondii infection in an acute murine model of
      toxoplasmosis. Diagnosis of tissue infection by Southern blot hybridization with
      cDNA clones of T. gondii was possible within 5 days of infection. This technique
      could detect as few as 10,000 organisms. Specific T. gondii gene amplification by
      PCR using the primers 5'CACACGGTTGTATGTCGGTTTCGCT3' and
      5'TCAAGGAGCTCAATGTTACAGCCT3' followed by oligonucleotide hybridization using
      5'GCGGTCATTCTCACACCGACGGAGAACCACTTCACTCTCA3' allowed detection of T. gondii in
      the tissue of mice by day 2 after infection and in the blood of mice by day 5
      after infection with RH strain T. gondii. This technique could detect as few as
      10 organisms. Thus, these techniques may be useful in the diagnosis of
      toxoplasmosis.

PMID- 1984467
TI  - Antimicrobial activity of an abundant calcium-binding protein in the cytoplasm of
      human neutrophils.
AB  - Studies of experimental infections in animals indicate that phagocytic cells may
      sometimes control infective foci without actually ingesting or contacting the
      invading microorganisms. In the present study, an effective inhibitor of Candida
      albicans growth, previously detected in neutrophils cytoplasm and found to be
      released only after lysis of the cells, was identified as an abundant calcium
      binding protein originally described in neutrophils as the L1 myelomonocytic
      antigen or the cystic fibrosis antigen. This substance was demonstrated also to
      have static activity against several other important human pathogens, including
      Aspergillus fumigatus, Staphylococcus aureus, and Escherichia coli. Growth of the
      various microorganisms was inhibited to considerably different degrees by the
      neutrophil protein, with the effects on S. aureus (the least responsive organism)
      being significantly enhance by addition of calcium to the medium. These findings
      suggest that after its release by the death of neutrophils at sites of tissue
      infection, this abundant calcium-binding protein could have a host defense
      function by controlling the growth of pathogenic microorganisms that escape being
      killed initially and would otherwise be free to proliferate.

PMID- 1984468
TI  - Predictive index for optimizing empiric treatment of gram-negative bacteremia.
AB  - In a survey of 296 episodes of gram-negative bacteremia in 286 patients (aged 13
      99 years), four clinical variables were found to predict both significantly and
      independently the subsequent isolation of a multiresistant strain; hospital
      acquisition of the infection, antibiotic treatment before the bacteremic episode,
      endotracheal intubation, and thermal trauma as the cause of hospitalization.
      These variables were combined in an index that served to classify the patients
      into four groups with an increasing prevalence of multiresistant strains,
      Pseudomonas isolates, and isolates resistant to each of the antibiotic drugs in
      common use. For example, the percentage of isolates susceptible to cefuroxime in
      the four groups were 79%, 56%, 34% and 25%, and to gentamicin, 89%, 79%, 46%, and
      33% (P less than .001 for both comparisons). The performance of the index was
      validated in a second group of 144 episodes of gram-negative bacteremia. The
      index kept its discriminative power. Compared with the prescriptions of the
      attending physicians, the index could probably have improved empiric antibiotic
      treatment in 24% of patients.

PMID- 1984469
TI  - Instillation of vancomycin into a cerebrospinal fluid reservoir to clear
      infection: pharmacokinetic considerations.
AB  - Vancomycin instilled in an Ommaya reservoir was used to treat a reservoir
      associated infection. Vancomycin concentrations in cerebrospinal fluid (CSF) were
      measured, and derivation of pharmacokinetic parameters allowed tailoring of
      dosing. First-order kinetics were observed. The calculated half-life of 3.52 h
      was less than reported by others, and the apparent volume of distribution (60 ml)
      was less than anticipated. The elimination constant was 0.197 h-1. Empiric dosing
      based on schedules suggested in the literature would have led to high peak and
      low mean concentrations of intrareservoir vancomycin. Patients with reservoir
      associated infections have a variety of pathophysiologic conditions that can
      result in alteration of normal CSF dynamics. Pharmacokinetic analysis is useful
      to individualize dosing and to optimize therapy with intrareservoir vancomycin.

PMID- 1984470
TI  - Guidelines for the use of antimicrobial agents in neutropenic patients with
      unexplained fever.

PMID- 1984471
TI  - Antimicrobial agents in neutropenic patients with unexplained fever.

PMID- 1984472
TI  - Vertical transmission of human T cell leukemia virus type I.

PMID- 1984473
TI  - Early resistance to rifampin and ciprofloxacin in the treatment of right-sided
      Staphylococcus aureus endocarditis.

PMID- 1984474
TI  - Exacerbation of bacterial toxicity to infant ferrets by influenza virus: possible
      role in sudden infant death syndrome.
AB  - Of several toxins examined, only staphylococcal alpha and gamma toxin, endotoxin,
      and diphtheria toxins were lethal for 5-day-old ferrets. Their toxicities were
      enhanced in animals infected at 1 day old with influenza virus, from 3-fold with
      staphylococcal gamma toxin through 14-fold for staphylococcal alpha toxin, 84
      fold for endotoxin, and 219-fold for diphtheria toxin. No increased viral
      replication occurred in any tissue; thus the effects of the toxins were
      exacerbated by the infection, not vice versa. Neonates died suddenly without
      clinical symptoms as in human babies dying from the sudden infant death syndrome
      (SIDS). Pathologic examination showed inflammation in the upper respiratory
      tract, lung edema and collapse, and early bronchopneumonia in the toxin- and
      influenza virus-treated animals but not in those treated with toxin or virus
      alone. Thus, bacterial toxins could play a role in SIDS, this being more likely
      with a concomitant influenza virus infection.

PMID- 1984475
TI  - Serologic discrimination of human T cell lymphotropic virus infection by using a
      synthetic peptide-based enzyme immunoassay.
AB  - Synthetic peptides corresponding with unique regions of the envelope
      glycoproteins (gp46) of human T cell lymphotropic viruses (HTLVs) were used in an
      enzyme immunoassay to determine if HTLV-I and -II infections could be
      discriminated. Two synthetic HTLV-I sequence-derived peptides, Env-1 (amino acids
      191-215) and Env-5 (amino acids 242-257), reacted with 92% and 100% of the serum
      specimens (n = 52) from HTLV-I-infected persons, respectively. Although a small
      percentage (8.6%) of serum specimens from persons infected with HTLV-II cross
      reacted with Env-1, none of these specimens reacted with Env-5. Peptide Env-2
      encoded by the envelope region of HTLV-II (amino acids 187-210) reacted with
      serum specimens from both HTLV-I (94%)- and HTLV-II (74%)-infected patients,
      whereas Env-6, another HTLV-II peptide (amino acids 238-254), reacted with less
      than 6% of the specimens. Therefore, the Env-5 peptide with amino acid sequence
      SerProAsnValSerValProSerSerSerSerThrProLeuLeuTyr represents an immunodominant
      domain of HTLV-I that is recognized by serum antibodies from all HTLV-I-infected
      persons. Moreover, the Env-5-based ELISA allows a categorical distinction between
      the closely related HTLV-I and -II infections.

PMID- 1984476
TI  - High incidence of antibodies to HTLV-I tax in blood relatives of adult T cell
      leukemia patients.
AB  - Adult T cell leukemia (ATL) is caused by the human T cell leukemia virus type I
      (HTLV-I). Although the mechanisms of the leukemogenic process are unknown, the
      tax gene may have a role in this process. Because clustering occurs with HTLV-I
      and ATL, members of ATL families were examined for antibodies to the tax protein
      and compared with matched HTLV-I-positive blood donors. To investigate the
      antibody response to this protein, a plasmid, pBHX-4, was constructed to express
      a recombinant tax protein (r-tax). For ATL patients and their HTLV-I antibody
      positive blood relatives, the rate of seroreactivity with the r-tax protein was
      67.3% (35/52), compared with 51.6% (97/188) for HTLV-I antibody-positive control
      blood donors (P less than .05). The difference between direct offspring of ATL
      patients and matched HTLV-I blood donors was even greater (84.2% [16/91] vs.
      44.2% [42/95]; P less than .005). Thus, tax antibody positivity in direct
      offspring of ATL patients may reflect differences in time or route of HTLV-I
      infection. Alternatively, it might reflect genetic differences in host
      susceptibility or virus strain.

PMID- 1984477
TI  - Use of a new CD4-positive HeLa cell clone for direct quantitation of infectious
      human immunodeficiency virus from blood cells of AIDS patients.
AB  - A new CD4-positive HeLa cell line (clone 1022) with increased sensitivity for
      human immunodeficiency virus (HIV) isolates derived from AIDS patients could
      titer infectivity of HIV from most isolates at a level equal to that observed
      using normal human phytohemagglutinin (PHA)-stimulated lymphocyte cultures. By
      use of this clone with a focal immunoassay (FIA), peripheral blood mononuclear
      cells (PBMC) producing HIV were detected in 15% of seropositive asymptomatic
      patients and 23% of AIDS patients at a frequency of 1 in 2 x 10(4) to 3 x 10(6)
      PBMC. HIV detection by primary FIA correlated with low CD4-positive cells counts.
      HIV activation in cocultures with PHA blasts resulted in increasing numbers of
      cells releasing HIV starting 3-4 days after cocultivation. The low incidence of
      HIV detection by direct FIA compared with the high incidence of HIV isolation
      after cocultivation with PHA blasts provided quantitative infectivity data
      suggesting that HIV was in a state of latency or low expression in most PBMC of
      AIDS patients.

PMID- 1984479
TI  - Tumor necrosis factor-alpha/cachectin enhances human immunodeficiency virus type
      1 replication in primary macrophages.
AB  - Macrophages are important target cells for human immunodeficiency virus type 1
      (HIV-1). The ability of HIV-1 to productively infect macrophages may be
      influenced by endogenous cytokines that alter the activation state of these
      cells. In this study, the effect of tumor necrosis factor-alpha/cachectin (TNF
      alpha), a cytokine with macrophage-activating properties, on HIV-1 replication in
      primary blood monocyte-derived macrophages was examined. Treatment of macrophages
      with recombinant human TNF alpha (rTNF alpha), starting before or after HIV-1
      infection, consistently enhanced viral production fivefold or greater above
      control (P less than .01). rTNF alpha was active at low concentrations (0.05-50
      ng/ml) and increased the replication of both lymphocyte-tropic (human T
      lymphotropic virus type IIIB) and macrophage-tropic (human T lymphotropic virus
      type III BaL) strains of HIV-1. These findings provide additional evidence that
      TNF alpha may play a role in the pathogenesis of HIV-1 infection by upregulating
      viral expression in macrophages.

PMID- 1984478
TI  - Interleukin-1-inhibitor activity induced by respiratory syncytial virus:
      abrogation of virus-specific and alternate human lymphocyte proliferative
      responses.
AB  - Respiratory syncytial virus (RSV) infection has been shown to induce human
      mononuclear leukocyte (MNL) production of net interleukin-1 (IL-1)-inhibitor
      activity. In the current studies of IL-1-inhibitor effects, RSV-exposed cells
      were compared with autologous MNL that were sham-exposed or exposed to
      inactivated RSV or influenza virus (which induces net IL-1 activity and commonly
      elicits effective homotypic immunity). Exposure of MNL to influenza virus or
      inactivated RSV resulted in increased expression of human leukocyte antigen-DR,
      the IL-2 receptor, and the transferrin receptor and increased progression through
      the cell cycle by 3 days. In contrast, exposure to infectious RSV resulted in
      decreased marker expression and cell cycle arrest, with abrogation of
      proliferation in response to the virus or other stimuli. These data raise the
      possibility that a contributing mechanism for recurrence of RSV infection is
      early suppression of the clonal expansion of virus-specific lymphocytes due to
      net IL-1-inhibitor activity.

PMID- 1984480
TI  - Divergent efficacy of antibody to tumor necrosis factor-alpha in intravascular
      and peritonitis models of sepsis.
AB  - The role of tumor necrosis factor-alpha (TNF alpha) in the lethal consequences of
      intravascular lipopolysaccharide (LPS) or Escherichia coli sepsis was compared
      with that in bacterial peritonitis. Intravenous administration of E. coli LPS or
      E. coli (live or dead) resulted in large transient increases in serum TNF alpha
      levels, peaking at 90 min at 10,000-30,000 units/ml. In contrast, the serum TNF
      alpha response following the induction of bacterial peritonitis was substantially
      less, peaking at 200-500 units/ml. Sterile peritonitis (essentially nonlethal)
      and bacterial peritonitis (greater than 60% lethal) elevated TNF alpha levels to
      1000-2000 units/lavage within the peritoneal cavity 2 h after challenge. Passive
      immunization with neutralizing goat anti-TNF alpha IgG improved survival from 8%
      to 75% in rats administered LPS intravenously but was completely ineffective in
      protecting rats from lethal E. coli peritonitis. Thus significant differences
      exist in the role TNF alpha plays in systemic intravascular models of sepsis and
      bacterial peritonitis.

PMID- 1984481
TI  - Pretreatment with ibuprofen augments circulating tumor necrosis factor-alpha,
      interleukin-6, and elastase during acute endotoxinemia.
AB  - Plasma levels of tumor necrosis factor-alpha (TNF alpha), interleukin-1 (IL-1),
      and interleukin-6 (IL-6) were monitored after intravenous administration of
      Escherichia coli endotoxin with or without ibuprofen pretreatment to healthy
      volunteers. Intravenous endotoxin (n = 7) resulted in elevated plasma TNF alpha
      concentrations with maximal levels at 90 min (369 +/- 44 pg/ml, P less than .001
      vs. saline controls, n = 7). The rise in TNF-alpha was followed by a rise in
      plasma IL-6 (27 +/- 12.8 ng/ml), peaking 30-90 min thereafter. Pretreatment with
      ibuprofen (n = 6) caused a significant augmentation and temporal shift in
      cytokine elaboration with maximal TNF alpha levels (627 +/- 136 pg/ml) at 120 min
      and IL-6 peaks (113 +/- 66 ng/ml) at 180 min. In ibuprofen-treated volunteers,
      the additional increase in TNF alpha was paralleled by increased levels of
      circulating elastase. In vitro experiments suggest a causal relationship between
      these events. Thus, the cyclooxygenase inhibitor ibuprofen blunts the clinical
      response to endotoxin but augments circulating cytokine levels and leukocyte
      degranulation.

PMID- 1984482
TI  - Tumor necrosis factor and severe malaria.
AB  - To investigate the relation of tumor necrosis factor-alpha (TNF alpha) to
      Plasmodium falciparum infection, plasma TNF alpha concentrations were measured in
      Zairian children with severe malaria, mild malaria, or other illnesses. The
      initial geometric mean plasma concentration of TNF alpha among 61 children with
      P. falciparum infection, (71 pg/ml) was higher than the level in 26 severely ill,
      aparasitemic children (10 pg/ml; P less than .001). Among 29 parasitemic
      children, initial geometric mean TNF alpha levels decreased from 77 to 5 pg/ml (P
      less than .001) at day 7. TNF alpha levels increased with parasite density and
      were associated with hyperparasitemia, severe anemia, hypoglycemia, and young age
      but not with cerebral malaria or fatal outcome. However, TNF alpha levels were
      elevated equally in children with cerebral malaria and with other signs of severe
      malaria. With multiple linear regression, TNF alpha levels were elevated
      independently in children with hyperparasitemia (P = .001) and severe anemia (P =
      .04). In this study, high TNF alpha levels were associated with several
      manifestations of severe malaria and were not specific to cerebral malaria.

PMID- 1984483
TI  - Palmitate-derivatized antibodies can specifically "arm" macrophage effector cells
      for ADCC.
AB  - The use of palmitate-derivatized antibodies (pal-Ab) for "arming" macrophage (M
      phi) effector cells for antibody-dependent cellular cytotoxicity (ADCC) is
      described. Pal-Ab were incorporated onto the M phi plasma membranes by insertion
      of the palmitate hydrocarbon chains into the outer leaflet of the phospholipid
      bilayer. M phi bearing pal-Ab specific for chicken erythrocytes (CE) mediated
      efficient destruction of the CE targets. Neither non-ADCC effector cell
      populations nor pal-Ab consisting of antibody F(ab')2 fragments effected
      significant CE lysis. M phi bearing pal-Ab that were not specific for CE did not
      mediate CE destruction, nor did anti-CE pal-Ab-bearing M phi lyse nonspecific
      human erythrocyte targets. In this system of effector cell arming, the palmitate
      anchor of pal-Ab allows for the incorporation of large numbers of antibodies onto
      the effector cell surface, where they can promote efficient target cell capture
      and engage preexisting or newly expressed FcR on the effector cell surface. The
      results in this study, together with those from previous and ongoing
      investigations in which F(ab')2 pal-Ab were shown to mediate Fc receptor (FcR)
      independent cytotoxicity by natural killer (NK) cells and M phi populations at
      appropriate states of activation, suggest that pal-Ab, by directing both ADCC and
      FcR-independent effector cell activity onto a specified target, offer important
      advantages over other methods of effector cell arming.

PMID- 1984484
TI  - Cystatin C and cathepsin B production by alveolar macrophages from smokers and
      nonsmokers.
AB  - The capacity of alveolar macrophages (AM) obtained from smokers and nonsmokers to
      secrete cathepsin B and its inhibitor cystatin C was examined because of the
      concept that an imbalance in the production of proteolytic enzymes and/or their
      inhibitors could be responsible for the lung damage seen in smokers. Quantitation
      of immunoprecipitates on Western blots showed that the amount of total cystatin C
      secreted into the culture medium by AM of smokers was significantly greater than
      the amount secreted by cells obtained from nonsmokers, whereas the difference
      between the amount of cathepsin B secreted by the AM of smokers and that from
      nonsmokers did not appear significant. The cystatin C found in the medium
      conditioned by AM of nonsmokers appeared to be more heterogeneous in molecular
      size, presenting either as a single band of about 14 Kd or as a high-molecular
      weight triplet of about 69 Kd, 63 Kd, and 57.3 Kd. Furthermore, in some cases
      there were single or doublet bands at 14 Kd as well as the high-molecular-weight
      triplets. In contrast, smokers AM-conditioned medium uniformly possessed both the
      low-and the high-molecular-weight cystatin C. Cathepsin B was not detected in
      Western blots at its reported molecular weights but was identified at the exact
      area occupied by the higher molecular weight cystatin C, i.e., at bands
      corresponding to 69 Kd, 63 Kd, and 57.3 Kd. Therefore, it is clear that in
      culture media of AM, cystatin C and cathepsin B are present as proteinase
      antiproteinase complexes. The observation also suggests that in smokers an excess
      of cystatin C may be elaborated, which, if further substantiated, would show for
      the first time a likely role for this proteinase inhibitor in vivo.

PMID- 1984485
TI  - Syngeneic B lymphoma cells provide a unique stimulus to natural killer (NK) cells
      in genetically low-NK SJL/J mice.
AB  - SJL/J mice are a genetically low-NK strain, and their cytotoxic activity cannot
      be augmented with conventional NK inducers. In contrast, effector cells taken
      from the lymphoid tissues of SJL mice bearing a syngeneic B cell lymphoma (RCS)
      show variable, but significant levels of cytotoxic activity against NK
      susceptible targets, such as YAC-1. Previous results suggested that the RCS cells
      themselves contributed to this cytotoxicity. However, results presented here
      indicate the most, if not all of the activity present within the lymphoid tissues
      of RCS-bearing mice is mediated by RCS-activated, host NK cells. These results
      were confirmed by in vitro studies, which demonstrate that both gamma irradiated
      (gamma-) RCS cells and gamma-allogeneic spleen cells induce cytotoxic activity in
      SJL spleen cells against YAC targets. However, the cytotoxicity induced by gamma
      allogeneic cells is mediated largely by lymphokine-activated killer (LAK) cells,
      since these effectors also lyse NK-resistant target cells, such as L1210. In
      contrast, the cytotoxic effector cells that are induced by syngeneic gamma-RCS
      cells cause lysis of YAC targets, but not L1210 target cells. These data indicate
      that the syngeneic B cell lymphomas of SJL mice are a unique stimulus for host NK
      cells in this strain. Since activated NK cells produce a variety of lymphokines,
      RCS stimulation of host NK cells in SJL mice may provide some of the growth
      promoting lymphokines that are known to be necessary for progressive growth of
      these lymphoma cells.

PMID- 1984486
TI  - Tumoricidal activity of alveolar and peritoneal macrophages of C57BL/6 mice
      bearing metastatic or nonmetastatic variants of Lewis lung carcinoma.
AB  - The spontaneous tumoricidal abilities of alveolar and peritoneal macrophages from
      C57B1/6 mice bearing a metastatic or a nonmetastatic cloned variant of Lewis lung
      carcinoma (LLC) were measured. Cytotoxicity by alveolar macrophages was enhanced
      during the first few weeks after subcutaneous (s.c.) or intravenous (i.v.)
      injection of metastatic LLC-C3 cells, but not after injection of nonmetastatic
      LLC-C8 cells. Alveolar macrophages from mice with s.c.-injected metastatic
      tumors, but not with nonmetastatic tumors, could be further activated in vitro,
      but not beyond the maximal level of spontaneous cytotoxicity. Late in tumor
      growth, the spontaneous cytotoxicity by alveolar macrophages of metastatic LLC-C3
      tumor bearers was suppressed and could not be increased by in vitro activation.
      The tumoricidal abilities of peritoneal macrophages from mice bearing either LLC
      C3 or LLC-C8 tumors were modulated in a similar way, as were alveolar
      macrophages. The reduced cytotoxicity by alveolar macrophages from mice with
      nonmetastatic tumors or from mice bearing large metastatic tumors was not due to
      suppression by macrophage-derived prostaglandins. The loss of tumoricidal
      capabilities by macrophages from mice with large metastatic LLC-C3 tumors was not
      caused by elevated systemic prostaglandin E2 (PGE2) levels. These results suggest
      that alveolar and peritoneal macrophages are activated to be cytotoxic during
      development of pulmonary metastases and do not need to be functionally depressed
      for successful establishment of metastases.

PMID- 1984487
TI  - Atlantoaxial stabilization in rheumatoid arthritis.
AB  - Atlantoaxial subluxation in patients with rheumatoid arthritis is common.
      Operative stabilization is clearly indicated when signs and symptoms of spinal
      cord compression occur. However, many recommend early operative fusion before
      evidence of appreciable neural compression occurs because 1) the myelopathy in
      these patients may be irreversible; 2) the overall prognosis is poor once
      symptoms of cord compression are present; and 3) the risk of sudden death
      associated with atlantoaxial subluxation is increased even in asymptomatic
      patients. The authors believe that rheumatoid arthritis patients in relatively
      good health without advanced multisystem disease and less than 65 years of age
      should be considered for operative stabilization if mobile atlantoaxial
      subluxation is greater than 6 mm. Seventeen patients with severe rheumatoid
      arthritis and atlantoaxial subluxation treated with a posterior arthrodesis are
      presented. A new method of fusion, devised by the senior author (V.K.H.S.), was
      utilized in all cases. Indications for operative therapy in these patients
      included evidence of spinal cord compression in 11 patients (65%) and mobile
      atlantoaxial subluxation greater than 6 mm but no signs or symptoms of cord
      compression in six patients (35%). Thirteen patients developed a stable osseous
      fusion, two patients a well-aligned fibrous union, one patient a malaligned
      fibrous union, and one patient died prior to evaluation of fusion stability. The
      details of the operative technique and management strategies are presented.
      Several technical advantages of this method of fusion make this approach
      particularly useful in patients with rheumatoid arthritis. Because of multisystem
      involvement of this disease, a high rate of osseous fusion is often difficult to
      achieve.

PMID- 1984488
TI  - Dopamine distribution and behavioral alterations resulting from dopamine infusion
      into the brain of the lesioned rat.
AB  - In an effort to verify the "dopamine secretion hypothesis" as the mechanism
      responsible for the antiparkinsonian efficacy of adrenal medullary transplants
      into the brain, the effects of dopamine infusion into the brains of rats with
      unilateral substantia nigra lesions were examined. The apomorphine-induced
      rotation, characteristic of this animal model, was diminished after 7 days of
      continuous dopamine infusion (10 micrograms/hr) into the ipsilateral striatum,
      whereas intraventricular infusion was without effect. Chromatographic analysis of
      the dopamine distribution after 10 days of infusion into either region revealed
      that ipsilateral delivery of dopamine did not result in contralateral increases
      in dopamine content. Examination of the adjacent striatum following ipsilateral
      intraventricular delivery indicated that dopamine had only penetrated 1 mm. Even
      with intrastriatal delivery, there were still parts of the infused striatum which
      had below-normal levels of dopamine. The fact that striatal tissue presents a
      significant barrier to the penetration of dopamine is discussed in relation to
      adrenal medullary and fetal nigral transplants.

PMID- 1984489
TI  - Tumor-associated neurological dysfunction prevented by lazaroids in rats.
AB  - The efficacy of U-74006F and U-78517F in the treatment of blood-tumor barrier
      permeability and tumor-associated neurological dysfunction was evaluated in a
      brain-tumor model in rats. U-74006F is a 21-aminosteroid and U-78517F is a 2
      methylamino chroman. Rats with stereotactically implanted Walker 256 tumors were
      treated with methylprednisolone, U-74006F, U-78517F, or vehicle (0.05 N HCl) on
      Days 6 through 10 following implantation. Neurological function and vascular
      permeability were assessed on Day 10. Methylprednisolone and U-74006F were
      equally effective at preventing neurological dysfunction compared to the control
      group (p less than 0.01); U-78517F was slightly less effective than U-74006F and
      methylprednisolone but was significantly better than vehicle in preventing
      neurological dysfunction. Delivery of methylprednisolone resulted in a
      significant decrease in tumor vascular permeability (p less than 0.006) while U
      74006F and U-78517F had no effect on permeability. This suggests that U-74006F
      and U-78517F prevented tumor-associated neurological dysfunction by a mechanism
      other than decreasing permeability in tumor capillaries, and that U-74006F or U
      78517F could prove useful in the treatment of brain tumors.

PMID- 1984490
TI  - Enhanced in vitro uptake and retention of 3H-tetraphenylphosphonium by nervous
      system tumor cells.
AB  - Photodynamic therapy is a promising treatment for human brain tumors because of
      the selective retention of certain compounds by tumor cells. Certain lipophilic
      cationic compounds, such as tetraphenylphosphonium (TPP), are selectively taken
      up by a variety of carcinomas. Although preferential retention of TPP has been
      demonstrated for the breast carcinoma cell line MCF-7, this compound had not been
      tested previously on cells derived from nervous system tumors. In the present
      study, tritiated-TPP (3H-TPP) uptake and retention for eight different cell
      cultures of three histologically different types of nervous system tumors was
      measured and the data were compared to a positive control (MCF-7) and negative
      controls (normal African Green monkey kidney epithelium (CV-1) and the normal
      human fibroblast (WI-38) cell lines). Uptake and retention characteristics could
      be grouped by specific pathological tumor types, but individual tumor variability
      was notable. Malignant astrocytoma (grade III/III glioblastoma) and malignant
      neurofibrosarcoma cells showed preferential uptake and retention of 3H-TPP
      relative to meningioma cells and normal controls. A clonogenic assay utilizing
      the cytotoxic lipophilic cationic compound dequalinium showed strong retainers of
      3H-TPP to be more susceptible to the effects of dequalinium than weak retainers.
      These data demonstrate that certain human and experimental animal nervous system
      tumor cell lines retain lipophilic compounds possessing a delocalized positive
      charge. Lipophilic cationic compounds may be useful in the intraoperative
      delineation of tumor margins and in the photodynamic therapy of certain nervous
      system tumors.

PMID- 1984491
TI  - Epidermoid cysts of the brain stem. Report of three cases.
AB  - The authors report the cases of three patients with epidermoid cysts which
      insinuated themselves into the brain stem. In all three patients, the tumor
      occupied the pons, although in one it was predominantly located in the medulla.
      The cyst contents and nonadherent tumor capsule were removed in all three
      patients, but no attempt was made to remove tumor densely adherent to the brain
      stem. One patient's cyst was removed in one operation, but maximal resection in
      the other two required two operations. After surgery, sixth nerve function
      completely returned in one patient; another patient had a stable pontine gaze
      palsy but developed new facial weakness; and the third patient had stable cranial
      nerve deficits with a diminished hemiparesis. The last patient developed a
      pseudomeningocele and communicating hydrocephalus, and required a lumboperitoneal
      shunt. In all three patients, computerized tomography scans demonstrated
      hypodense tumors not enhanced by contrast material. Magnetic resonance imaging
      was performed on two patients; in both, the tumors showed increased signal
      intensity relative to brain on T1-weighted images and decreased signal intensity
      relative to brain on T2-weighted studies. Magnetic resonance imaging, the most
      accurate modality for localizing these lesions and determining their extent, was
      also invaluable for postoperative monitoring and follow-up evaluation. Safe and
      adequate resection includes decompression of cyst contents and removal of
      nonadherent portions of the cyst capsule. Cyst wall adherent to the brain stem,
      however, should not be removed.

PMID- 1984492
TI  - Pseudopsammomatous meningioma with elevated serum carcinoembryonic antigen: a
      true secretory meningioma. Case report.
AB  - A sphenoid-wing meningioma in a 60-year-old woman was accompanied by elevated
      serum carcinoembryonic antigen (CEA) levels, which returned to normal after
      removal of the tumor. Light microscopic examination revealed a secretory
      meningioma containing numerous pseudopsammoma bodies and a prominent vascular
      pattern. Immunohistochemical analysis showed the tumor cells and pseudopsammoma
      bodies to be CEA-positive. This case illustrates the possibility that secretory
      meningioma may be associated with clinically detectable secretion of CEA. The
      report also documents the rare occurrence of elevated serum CEA in a primary
      benign intracranial tumor.

PMID- 1984493
TI  - Occlusion of an "accessory" distal anterior cerebral artery during treatment of
      anterior communicating artery aneurysms. Report of two cases.
AB  - Two cases are presented in which clip occlusion of a third distal anterior
      cerebral artery segment occurred during treatment of anterior communicating
      artery aneurysms. Case histories, angiograms, operative descriptions, and
      postmortem findings are presented. The incidence of this anomalous vessel is
      reviewed. Preoperative and intraoperative vigilance in determining the presence
      of this anomaly prior to clip placement is emphasized.

PMID- 1984494
TI  - Basilar impression in osteogenesis imperfecta tarda. Case report.
AB  - A case is presented of basilar impression secondary to osteogenesis imperfecta
      tarda, associated with hemifacial spasm and brain-stem compression syndrome. The
      symptoms improved with posterior fossa decompression and posterior fusion.

PMID- 1984495
TI  - Tension pneumocephalus: treatment with controlled decompression via a closed
      water-seal drainage system. Case report.
AB  - The successful treatment of a patient with tension pneumocephalus by controlled
      decompression via external drainage is described. The advantage of the technique
      includes the immediate release of high pressure and the capability of maintaining
      constant low pressure to enable and facilitate sealing of dural tears. The method
      has been used in three other patients, leading to resolution of the tension
      pneumocephalus without recurrence or other complications.

PMID- 1984497
TI  - Movement of hemostatic clips from the ventricles through the aqueduct to the
      lumbar spinal canal. Case report.
AB  - The authors report a patient in whom rebleeding after operation for a left
      temporal arteriovenous malformation resulted in the dislocation of multiple
      hemostatic clips. Several clips, including a Yasargil aneurysm clip, were
      detected incidentally in the lumbar spinal canal. No clinical signs or symptoms
      were noted. Retrospectively, passage of the aneurysm clip through the aqueduct
      could be detected on computerized tomography scans performed to evaluate a series
      of epileptic seizures.

PMID- 1984496
TI  - Risks factors for cerebral infarction in good-grade patients after aneurysmal
      subarachnoid hemorrhage and surgery: a prospective study.
AB  - A prospective series of 265 patients with aneurysmal subarachnoid hemorrhage
      (SAH) of Grades I to III (Hunt and Hess classification) upon admission were
      evaluated as to neurological outcome and computerized tomography (CT) findings 1
      to 3 years (mean 1.4 years) after the SAH and surgery. A total of 73 patients
      underwent acute surgery (within 72 hours after the bleed: Days 0 to 3), 86 were
      operated on subacutely (between Days 4 and 7), and 91 had late surgery (on Day 8
      or later). Fifteen patients died before surgery was undertaken and another 20
      patients died during the follow-up period. A total of 104 patients received
      nimodipine and the rest of the patients received either placebo (109 patients) or
      no medication (52 patients). A logistical regression analysis revealed the
      following prognostic factors for cerebral infarction, in order of importance: the
      amount of blood on the primary CT scan; postoperative angiographic vasospasm; the
      timing of the operation; and a history of hypertension. The use of nimodipine was
      associated with a significant reduction of cerebral infarcts visualized by CT
      scanning in patients who received intermediate or late surgery. In patients who
      underwent acute surgery no significant difference between the incidence of
      cerebral infarcts was observed.

PMID- 1984498
TI  - The fastigial pressor response. Case report.
AB  - A distinct vasomotor and cardioregulatory response first identified
      experimentally was elicited intraoperatively in a 6-year-old girl by local
      mechanical stimulation in the vicinity of the fastigial nucleus of the
      cerebellum. These findings are discussed in the light of current experimental
      knowledge of the anatomy and physiology of the fastigial pressor response.

PMID- 1984499
TI  - Cerebrospinal fluid rhinorrhea following acoustic neurinoma surgery. Technical
      note.
AB  - The authors describe a method of preventing cerebrospinal fluid (CSF) rhinorrhea
      following surgery for acoustic neurinoma. Mastoid air cells exposed during
      craniectomy are skeletonized and packed with bone dust, then covered with
      Surgicel soaked with Tisseel fibrin glue. The use of this technique has reduced
      the number of acoustic neurinoma cases requiring secondary mastoidectomy for CSF
      leakage from 16% to 5%.

PMID- 1984500
TI  - Vein bypass grafts and basofrontal mass lesions.

PMID- 1984501
TI  - Tissue grafting and immunosuppression.

PMID- 1984502
TI  - Reduced platelet aggregability and thromboxane release after rebleeding in
      patients with subarachnoid hemorrhage.
AB  - Serial blood samples were obtained from 80 patients with subarachnoid hemorrhage
      (SAH) to study adenosine diphosphate-induced platelet aggregation and associated
      thromboxane B2 release. The goal of the investigation was to detect whether
      reduced platelet function is involved in rebleeds. Seventeen patients (21%)
      suffered a rebleed, six of those experiencing their first rebleed within 24 hours
      after SAH. Therefore, most platelet function studies were performed after
      rebleeds. Thromboxane release was lower in patients with rebleeds than in the
      others, both before and after rebleeding, although statistical significance was
      reached only in samples collected after rebleeds. Patients rebleeding within 24
      hours after SAH had lower platelet aggregability (p = 0.037) than patients
      without a rebleed in the samples taken within 3 days after SAH. The results
      suggest that reduced platelet aggregability and thromboxane release are involved
      in rebleeds following primary SAH.

PMID- 1984503
TI  - Correlates of survival and the Daumas-Duport grading system for astrocytomas.
AB  - In order to examine the correlation between prognosis and the histological
      features of nuclear atypia, mitosis, endothelial proliferation, and necrosis in
      supratentorial adult astrocytomas, the authors reviewed 251 such cases treated at
      the Massachusetts General Hospital between 1972 and 1980. One point was given for
      the presence of each feature. The total number of features was translated into a
      grade as follows: none of the four features = Grade 1 (one patient), one feature
      = Grade 2 (36 patients), two features = Grade 3 (33 patients), and three or four
      features = Grade 4 (181 patients). The period of survival was significantly
      associated with grade, the presence or absence of each of the four histological
      features, patient's age, type of operation, radiation therapy, and extent of
      tumor (log rank, p less than 0.05). The variables associated with grade were age
      (p less than 0.001) and radiation therapy (p less than 0.02). After adjustment
      for these variables using a Cox proportional-hazards model, the difference in
      overall survival time between patients in Grades 2 and 3 was not statistically
      significant. When comparable groups of patients were examined in terms of age or
      receipt of radiation therapy, the median survival times differed markedly.
      Patients 50 years of age or less had a median survival time of 68 months (Grade 2
      tumors), 29 months (Grade 3 tumors), and 13 months (Grade 4 tumors). Patients
      over 50 years of age had a median survival time of 6 months (Grade 2 and 4
      tumors) and 9 months (Grade 3 tumors). Those patients who had received radiation
      therapy had a median survival time of 68 months (Grade 2 tumors), 21 months
      (Grade 3 tumors), and 11 months (Grade 4 tumors). Those patients who did not
      receive radiation therapy had a median survival time of 1 month (Grade 2 tumors)
      and 2 months (Grade 3 and 4 tumors); over half of these patients died within 2
      months of surgery. This grading system, originally proposed by Daumas-Duport, et
      al., is simple, objective, and reproducible, and correlates well with survival
      times. The authors recommend that astrocytomas be graded on a scale of 1 to 4,
      with Grade 1 reserved for the rare adult supratentorial astrocytoma with none of
      the four histological features.

PMID- 1984504
TI  - Idiopathic and glucocorticoid-induced spinal epidural lipomatosis.
AB  - Pathological overgrowth of the epidural fat in the spine has been described and
      reported nearly exclusively in patients either with Cushing's syndrome or on
      chronic intake of glucocorticoids for a variety of clinical disorders. The
      authors report four patients with documented spinal lipomatosis (three
      pathologically and one radiologically). Only one of these patients received
      corticosteroids, and none had an underlying endocrinological abnormality. All
      four patients were adult males with a mean age at onset of symptoms of 43 years
      (range from 18 to 60 years). The symptoms ranged from simple neurogenic
      claudication and radicular pain to frank myelopathy. Myelography followed by
      computerized tomography were instrumental in the diagnosis of the first three
      patients; the fourth was diagnosed by magnetic resonance imaging. The thoracic
      spine was involved in two cases and the lumbosacral area in the other two. The
      different treatment modalities were tailored according to the symptomatology of
      the patients. These included weight reduction of an overweight patient with
      minimal neurological findings in one case and decompressive laminectomy and fat
      debulking to achieve adequate cord decompression in the remaining three cases.
      Two patients improved significantly, the condition of one stabilized, and the
      fourth required a second decompression at other spinal levels. The various
      modalities of treatment and their potential complications are discussed.

PMID- 1984505
TI  - The effect of glucose administration on carbohydrate metabolism after head
      injury.
AB  - The role of intravenous infusion of glucose in limiting ketogenesis and the
      effect of glucose on cerebral metabolism following severe head injury were
      studied in 21 comatose patients. The patients were randomly assigned to
      alimentation with or without glucose. Systemic protein wasting, arterial
      concentrations of energy substrates, and cerebral metabolism of these energy
      substrates were monitored for 5 days postinjury. Both groups were in negative
      nitrogen balance, and had wasting of systemic proteins despite substantial
      protein intake. Blood and cerebrospinal fluid (CSF) glucose concentrations were
      highest on Day 1, but remained higher than normal fasting levels on all days of
      study, even in the patients who received no exogenous glucose. Although there
      were no differences in blood or CSF glucose concentrations in the two groups of
      patients, the glucose group had higher plasma insulin levels, with a mean +/-
      standard deviation of 14.8 +/- 7.3 microU/ml compared to 10.3 +/- 4.2 microU/ml
      in the saline group. The blood concentrations of beta-hydroxybutyrate,
      acetoacetate, pyruvate, glycerol, and the free fatty acids were higher in the
      saline group than in the glucose group. Cerebral oxygen consumption was similar
      in the two groups, while the cerebral metabolism of glucose and of the ketone
      bodies was dependent on whether glucose was administered. In the glucose group,
      glucose was the only energy substrate utilized by the brain. In the saline group,
      the ketone bodies beta-hydroxybutyrate and acetoacetate replaced glucose to the
      extent of 16% of the brain's total energy production. Cerebral lactate production
      and CSF lactate concentration were lower in the saline group. These studies
      suggest that administration of glucose during the early recovery period of severe
      head injury is a major cause of suppressed ketogenesis, and may increase
      production of lactic acid by the traumatized brain by limiting the availability
      of nonglycolytic energy substrates.

PMID- 1984506
TI  - Long-term outcome following anterior cerebral artery ligation for ruptured
      anterior communicating artery aneurysms.
AB  - The long-term prognosis (15 years) was determined for 17 patients who had
      undergone anterior cerebral artery (ACA) ligation as the sole treatment for an
      anterior communicating artery aneurysm. The number of early and late rebleeds was
      lower than expected from previously ruptured aneurysms. Late ischemia was not a
      major complication while late postoperative epilepsy occurred in 19% of
      survivors. In a review of previously published series, ACA ligation appears to
      have significantly reduced the rates of both early and late rebleeding. This
      study helps to define the late results of "conservative" operations for ruptured
      aneurysms.

PMID- 1984507
TI  - Intratumoral oxygen pressure in malignant brain tumor.
AB  - Oxygen pressure (pO2) in brain tumors, pO2 in brain cortex surrounding the
      tumors, and PaO2 were measured simultaneously during total resection in 16
      patients with previously untreated brain tumors in order to detect hypoxic
      regions within the tumors. When the inhaled O2:N2O ratio was 1:3 under enflurane
      anesthesia, mean PaO2 was 109.2 +/- 5.8 mm Hg, a rather high value when compared
      with that obtained when air is inhaled under atmospheric pressure. The
      simultaneously measured intratumoral pO2 and pO2 in brain cortex surrounding the
      tumor were 15.3 +/- 2.3 and 59.8 +/- 6.5 mm Hg, respectively. Each intratumoral
      pO2 value was significantly lower than that of pO2 in brain cortex surrounding
      the tumor (mean less than 30 mm Hg, Wilcoxon signed rank test, p less than 0.005)
      and influenced the oxygen effects on radiation. These results appear to confirm
      that there are hypoxic regions within human brain tumors. A comparison between
      intratumoral pO2 and either the angiographic or contrast-enhanced computerized
      tomography scans of the tumor vasculature disclosed no correlation.

PMID- 1984508
TI  - Iopamidol myelography: morbidity in patients with previous intolerance to iodine
      derivatives.
AB  - The records of 1005 patients who underwent iopamidol myelography between January
      and September, 1988, were reviewed. In this group, 50 patients had histories
      suggestive of untoward sequelae associated with iodine intake, contact, or
      administration. The charts of these patients were carefully reviewed, and none of
      them had any reactions or sequelae suggestive of toxicity or an allergic response
      after iopamidol myelography. It is concluded that, even in patients with a
      previous history suggestive of intolerance to iodine administration, iopamidol
      myelography is generally a safe procedure.

PMID- 1984509
TI  - Shunt surgery for hydrocephalus in tuberculous meningitis: a long-term follow-up
      study.
AB  - Hydrocephalus is a common complication of tuberculous meningitis. Case studies of
      114 patients with tuberculous meningitis and hydrocephalus, who underwent shunt
      surgery between July, 1975, and June, 1986, were reviewed to evaluate the long
      term outcome and to outline a management protocol for these patients based on the
      results. Seven factors were studied in each case: 1) age at admission; 2) grade
      on admission (I to IV, classified by the authors; Grade I being the best and
      Grade IV being the worst); 3) duration of alteration of sensorium; 4)
      cerebrospinal fluid (CSF) cell content at initial examination; 5) CSF protein
      levels at initial examination; 6) number of shunt revisions required; and 7) the
      necessity for bilateral shunts. During a long-term follow-up period ranging from
      6 months to 13 years (mean 45.6 months), the mortality rate was 20% for patients
      in Grade I; 34.7% for patients in Grade II; 51.9% for patients in Grade III; and
      100% for patients in Grade IV. Only the grade at the time of admission was found
      to be statistically significant in determining final outcome (p less than 0.001).
      Based on these results, the authors advocate early shunt surgery for Grade I and
      II patients. For patients in Grade III, surgery may be performed either if
      external ventricular drainage causes an improvement in sensorium or without
      selection. All patients in Grade IV should undergo external ventricular drainage
      and only those who show a significant change in their neurological status within
      24 to 48 hours of drainage, should have shunt surgery.

PMID- 1984510
TI  - Management of meralgia paresthetica.
AB  - Meralgia paresthetica is a syndrome of pain or dysesthesia, or both, in the
      anterolateral thigh caused by entrapment or neurinoma formation of the lateral
      femoral cutaneous nerve. Conservative treatment was successful in relieving
      symptoms in 91% of 277 patients with this syndrome; however, 24 patients required
      surgical treatment for intractable symptoms. Although neurolysis with
      transposition is the most common procedure, sectioning of the lateral femoral
      cutaneous nerve was performed in 24 cases and was successful in 23. One patient
      had early symptomatic relief, but subsequently developed different neurological
      signs and symptoms because of an undetected pelvic neoplasm. Anatomical
      variations of the nerve and neurinomas, which occur frequently, are easily
      handled with sectioning but may lead to recurrence with neurolysis and
      transposition.

PMID- 1984511
TI  - Long-term effects of nimodipine on cerebral infarcts and outcome after aneurysmal
      subarachnoid hemorrhage and surgery.
AB  - A total of 213 patients with verified aneurysmal subarachnoid hemorrhage (SAH) of
      Grades I to III (Hunt and Hess classification) were enrolled in a double-blind
      placebo-controlled trial to determine the effect of intravenous nimodipine on
      delayed ischemic deterioration and computerized tomography (CT)-visualized
      infarcts after SAH and surgery. The administration of the drug or matching
      placebo was started immediately after the radiological diagnosis of a ruptured
      aneurysm had been made. Of the 213 patients enrolled in the study, 58 were
      operated on early (within 72 hours after the bleed: Days 0 to 3), 69 were
      operated on subacutely (between Days 4 and 7), and 74 had late surgery (on Day 8
      or later). Eleven patients died before surgery was undertaken and one was not
      operated on. A follow-up examination with CT scanning, performed 1 to 3 years
      after the SAH (mean 1.4 years), revealed no significant differences in the
      overall outcome between the groups. However, nimodipine treatment was associated
      with a significantly lower incidence of deaths caused by delayed cerebral
      ischemia (p = 0.01) and significantly lower occurrence of cerebral infarcts
      visualized by CT scanning in the whole population (p = 0.05), especially in
      patients without an associated intracerebral hemorrhage on admission CT scan (p =
      0.03).

PMID- 1984512
TI  - Treatment of severe intraventricular hemorrhage by intraventricular infusion of
      urokinase.
AB  - Six patients with severe intraventricular hemorrhage were treated with direct
      intraventricular infusion of urokinase. In each case, hemorrhage extended into
      all ventricular chambers, and a cast formation and expansion of the third and
      fourth ventricles were found. Immediately after the therapy was started (within 7
      days from onset of symptoms), reduction of intraventricular hematoma volume was
      observed on computerized tomography. On average, both the third and fourth
      ventricles became clear on the third day after hemorrhage; there was one
      exception, a case of ruptured aneurysm. Five of the six patients showed excellent
      or good outcome, although two developed delayed hydrocephalus. No infection or
      rebleeding was observed. The outcome in a retrospectively studied group of five
      patients not treated with urokinase is also reported. The authors conclude that
      this relatively easy method of treatment will greatly improve the prognosis of
      severe intraventricular hemorrhage.

PMID- 1984513
TI  - Effects of tromethamine and hyperventilation on brain injury in the cat.
AB  - The metabolic brain acidosis after trauma has been thought to be harmful and to
      contribute to neurological deterioration. Amelioration of the brain acidosis
      either by systemic buffering agents or by hyperventilation has been proposed as a
      method of treatment. The objective of this study was to explore with magnetic
      resonance (MR) spectroscopy the metabolic changes in brain that occur with the
      use of hyperventilation, THAM (tromethamine; tris[hydroxymethyl]aminomethane),
      and a combination (THAM and hyperventilation) therapy in experimental fluid
      percussion injury. Brain lactate, brain pH, inorganic phosphate (Pi), and
      adenosine triphosphate levels were measured by 1H and 31P MR spectroscopy.
      Arterial and cerebrovenous lactate and water content in brain tissue was
      determined in 29 cats using the specific gravimetric technique. Following injury,
      the phosphocreatine (PCr)/Pi ratio, which is an index of cerebral energy
      depletion, decreased to 76% in four untreated animals, to 79% in 11 THAM-treated
      animals, to 68% in seven animals receiving hyperventilation, and to 66% in seven
      animals with combination THAM and hyperventilation therapy. The PCr/Pi ratio
      returned to a normal level in 8 hours in animals treated with THAM and THAM in
      combination with hyperventilation. The brain lactate index increased to 157% in
      the hyperventilation group after trauma. In cats receiving THAM plus
      hyperventilation, the brain lactate index was reduced to 142%, while the minimum
      rise of 126% was associated with treatment of THAM alone. In the THAM-treatment
      and combination-treatment groups, the water content of the white and gray matter
      was significantly decreased compared with that in untreated cat brains. Prolonged
      hyperventilation provided relative ischemia in brain tissue and promoted more
      production of brain lactate, no recovery of the PCr/Pi ratio, and no decrease in
      brain edema. On the other hand, administration of THAM decreased production of
      brain lactate and brain edema and promoted the recovery of cerebral energy
      dysfunction. It was found that THAM ameliorates the deleterious effects of
      hyperventilation by minimizing energy disturbance and that it also decreases
      brain edema. The authors conclude that THAM may be effective in reducing brain
      tissue acidosis and helpful as a metabolic stabilizing agent following severe
      head injury.

PMID- 1984514
TI  - Sex, trials, and datatapes.

PMID- 1984515
TI  - Effect of prior cancer chemotherapy on human tumor-specific cytotoxicity in vitro
      in response to immunopotentiating biologic response modifiers.
AB  - Tumor-specific cytotoxicity was measured in fresh human biopsy specimens by a
      modification of the differential staining cytotoxicity assay. ImuVert, a cytokine
      inducer derived from Serratia marcescens, which produces broad-spectrum
      activation of both macrophages and lymphocytes, was dramatically more effective
      when it was tested in tumors obtained from patients with previously treated,
      chemotherapy-responsive adenocarcinomas (breast and ovary) than when it was
      tested in tumors obtained from either previously untreated patients or previously
      treated patients with chemotherapy-refractory adenocarcinomas (colon, lung,
      pancreas, stomach, kidney, gallbladder, uterus, and prostate). Similar findings,
      relating to prior chemotherapy treatment status, were obtained for tumor necrosis
      factor and interferon gamma, but not for interleukin-2 or interferon alpha. On
      the basis of these findings and on other evidence in the literature, we speculate
      that response to chemotherapy produces massive release and processing of tumor
      antigens. We further speculate that this response leads to a state in which the
      human immune system is primed (via in situ vaccination) to respond to exogenous
      macrophage-activation signals with potent, specific antitumor effects.

PMID- 1984516
TI  - Elevated expression of the c-fes proto-oncogene in adult human myeloid leukemia
      cells in the absence of gene amplification.
AB  - Expression of the 93-kd tyrosine kinase encoded by the human c-fes proto-oncogene
      (also known as FES) is restricted to mature hematopoietic cells of the
      granulocytic and monocytic lineages, suggestive of a function essential to normal
      myeloid differentiation. However, recent studies have shown that c-fes can
      transform fibroblasts if sufficient levels of gene expression are achieved. These
      findings indicate that strict regulation of the c-fes gene is critical to normal
      myeloid development, whereas elevated c-fes expression may contribute to
      malignant transformation. In the present study, we compared the c-fes messenger
      RNA (mRNA) levels in leukemia blasts from patients with myeloid or lymphoid
      leukemia with those of peripheral monocytes from a normal donor with the use of a
      quantitative ribonuclease protection assay. The presence of c-fes mRNA was
      readily detected in both acute myeloid leukemia (AML) and chronic myeloid
      leukemia (CML) cells, but c-fes mRNA was present in low levels or was absent in
      lymphoid leukemia cells. The leukemia cells of two of five AML patients and four
      of four CML patients expressed more c-fes mRNA than monocytes from a normal
      donor, with more than a threefold elevation in the cells of one CML patient. No
      evidence of amplification or rearrangement of the c-fes gene was detectable by
      Southern blot analysis of myeloid leukemia DNA, suggesting that the variation in
      c-fes mRNA levels are related to differences in transcriptional activity and/or
      message stability. These results indicate that elevated c-fes expression is a
      common feature of myeloid leukemia cells that could potentially contribute to the
      leukemia phenotype.

PMID- 1984517
TI  - Comparisons of diet and biochemical characteristics of stool and urine between
      Chinese populations with low and high colorectal cancer rates.
AB  - In an investigation of the roles of diet and stool biochemistry in human
      colorectal carcinogenesis, 24-hour food, urine, and stool samples were collected
      from randomly selected participants from two populations with a fourfold
      difference in colorectal cancer risk: Chinese in Sha Giao, People's Republic of
      China (low risk), and Chinese-Americans of similar ages in San Francisco County,
      Calif, in the United States (high risk). The findings supported the hypotheses
      that colorectal cancer risk is increased by the consumption of high-fat, high
      protein, and low-carbohydrate diets and is associated with high levels of
      cholesterol in stool as well as increased daily outputs of 3-methyl-histidine and
      malonaldehyde in urine. However, risk does not increase with low stool bulk and
      low total stool fibers.

PMID- 1984518
TI  - Phase I trial of piritrexim capsules using prolonged, low-dose oral
      administration for the treatment of advanced malignancies.
AB  - A phase I trial of piritrexim was conducted by use of a prolonged, low-dose oral
      schedule. A number of different regimens were tested, including daily dosing for
      21 days followed by 7 days of no drug therapy; continuous dosing; and daily
      dosing for 5 of 7 days for 3 consecutive weeks followed by a week of rest. Dose
      escalation was accomplished by increasing the dosing frequency from once a day to
      twice a day and then to three times a day and by increasing the number of days of
      administration. Fifty-one patients with advanced cancer were entered in the
      study. One hundred twenty-four (96%) of 129 courses were considered assessable.
      Myelosuppression proved to be the dose-limiting toxic effect. Other toxic effects
      included stomatitis, nausea and vomiting, anorexia, diarrhea, skin rash, fatigue,
      and elevation of liver transaminase levels. Antitumor activity was observed in
      patients with melanoma and bladder cancer, and disease stabilization occurred in
      those with sarcoma and pheochromocytoma. The recommended dosing schedule for
      phase II clinical trials is 25 mg three times a day for 5 days for 3 consecutive
      weeks followed by 1 week of no drug therapy.

PMID- 1984519
TI  - Life-threatening bullous skin eruptions during interleukin-2 therapy.

PMID- 1984520
TI  - New technologies profoundly change cancer research in 20 years.

PMID- 1984521
TI  - Tamoxifen and estrogen replacement therapy as agents of disease prevention.

PMID- 1984522
TI  - Heredity as a determining factor in which smokers die of lung cancer.

PMID- 1984523
TI  - Providers to advise of 'medical Miranda'.

PMID- 1984524
TI  - Alzheimer's-linked protein found to be skin deep, but potential new therapies see
      beauty of it.

PMID- 1984526
TI  - State of 'Desert Shield' military medicine at deadline time in the Middle East
      crisis.

PMID- 1984525
TI  - Is it 'oldtimer's disease' or just growing old?

PMID- 1984527
TI  - From the Centers for Disease Control. Mortality from Alzheimer disease--United
      States, 1979-1987.

PMID- 1984528
TI  - From the Centers for Disease Control. Imported malaria associated with
      malariotherapy of Lyme disease--New Jersey.

PMID- 1984529
TI  - From the Centers for Disease Control. Acquired immunodeficiency syndrome--Europe.

PMID- 1984530
TI  - A piece of my mind. Mercy killing: mercy for whom?

PMID- 1984531
TI  - Family consent to orders not to resuscitate.

PMID- 1984532
TI  - Improvement in AIDS case reporting, South Carolina.

PMID- 1984533
TI  - The risks of drowning: males in Maryland rivers.

PMID- 1984534
TI  - Effectiveness and tolerance of long-term malaria prophylaxis with mefloquine.
      Need for a better dosing regimen.
AB  - To measure the effectiveness and tolerance of long-term malaria prophylaxis with
      mefloquine, the incidence of Plasmodium falciparum malaria and of adverse
      reactions was compared in Peace Corps volunteers in West Africa who took
      mefloquine every 2 weeks and in volunteers who took chloroquine phosphate weekly.
      Mefloquine was only 63% more effective than chloroquine; the monthly incidence of
      P falciparum infections was one case per 100 volunteers who took mefloquine and
      2.7 cases per 100 volunteers who took chloroquine. Using daily proguanil
      (chloroguanide) hydrochloride in addition to chloroquine did not provide
      additional protection. All mefloquine prophylaxis failures occurred during the
      second week of the every-2-weeks dosing regimen in volunteers who had used
      mefloquine for more than 2 months. Blood concentrations of mefloquine were lower
      during the second week of the alternate-week regimen than during the first week,
      suggesting that blood levels are too low during the second week to suppress
      parasitemia. No serious adverse reactions were observed. The results indicate
      that a dosing regimen of 250 mg of mefloquine weekly should be considered for
      travelers to areas with chloroquine-resistant P falciparum malaria.

PMID- 1984535
TI  - Contaminant blood cultures and resource utilization. The true consequences of
      false-positive results.
AB  - To determine whether contaminant blood cultures increase resource utilization, we
      studied charge and length of stay data for episodes in which blood cultures were
      obtained from hospitalized adults. Compared with 1097 negative episodes, 94 false
      positive episodes were associated with increased subsequent length of stay
      (median, 12.5 vs 8 days) and subsequent total charges (median, $13,116 vs $8731),
      pharmacy charges (median, $1456 vs $798), and laboratory charges (median, $2057
      vs $1426). In multivariate analyses, contaminants were independently correlated
      with 20% and 39% increases in total subsequent laboratory charges and intravenous
      antibiotic charges, respectively. Thus, the true costs of contaminants may
      greatly exceed those of the test itself. Identifying patients at very low risk of
      bacteremia and attention to sterile technique may reduce costs by decreasing the
      frequency of contaminants.

PMID- 1984536
TI  - Thiazide diuretics and the risk of hip fracture. Results from the Framingham
      Study.
AB  - Thiazide diuretics may preserve bone mass and prevent elderly women's osteopenic
      fractures, but studies have not distinguished between thiazide preparations or
      examined former users. We performed a case-control study looking at thiazide use
      and subsequent hip fracture in postmenopausal female members of the Framingham
      Study cohort. Cases who had experienced a first hip fracture (n = 176) were
      compared with age-matched controls (n = 672). Results showed a modest protective
      effect of any recent thiazide use (not significant). However, recent pure
      thiazide users experienced significant protection against fracture (adjusted odds
      ratio, 0.31; 95% confidence interval, 0.11 to 0.88), whereas recent users of
      combination drugs containing thiazides experienced no protection (adjusted odds
      ratio, 1.16; 95% confidence interval, 0.44 to 3.05). Combination drugs generally
      contained only 25 mg of hydrochlorothiazide, suggesting that the small amount of
      thiazide was insufficient to preserve bone mass. Former thiazide users were not
      protected against fracture. In sum, recent pure thiazide use in women protects
      against hip fracture.

PMID- 1984537
TI  - Comparison of uninsured and privately insured hospital patients. Condition on
      admission, resource use, and outcome.
AB  - To investigate the association between insurance status and condition on
      admission, resource use, and in-hospital mortality, we analyzed discharge
      abstracts for 592,598 patients hospitalized in 1987 in a national sample of
      hospitals. In 13 of 16 age-sex-race-specific cohorts, the uninsured had a 44% to
      124% higher risk of in-hospital mortality at the time of admission than did the
      privately insured. After controlling for this difference, the actual in-hospital
      death rate was 1.2 to 3.2 times higher among uninsured patients in 11 of 16
      cohorts. The uninsured also were 29% to 75% less likely to undergo each of five
      high-cost or high-discretion procedures and 50% less likely to have normal
      results on tissue pathology reports for biopsies performed during five of seven
      different endoscopic procedures. Our results suggest that insurance status is
      associated with a broad spectrum of aspects of hospital care.

PMID- 1984538
TI  - A minimalist policy for breast cancer surveillance.

PMID- 1984539
TI  - Imported Plasmodium falciparum malaria in American travelers to Africa.
      Implications for prevention strategies.
AB  - Data from the US National Malaria Surveillance System were analyzed to assess
      characteristics of travelers who acquired Plasmodium falciparum infections in
      Africa and evaluate the impact of chloroquine resistance on the incidence of
      imported malaria. Although the number of cases acquired in East Africa has
      stabilized, the number of imported P falciparum infections acquired in West
      Africa increased threefold from 1985 to 1988, and the proportion of travelers who
      reported failure of chloroquine prophylaxis increased from 10% to 48%. Fifty
      eight percent of patients who acquired malaria in West Africa had not used
      chemoprophylaxis. To curb the rising incidence of P falciparum infections in
      American travelers, the Centers for Disease Control revised malaria prophylaxis
      recommendations to include the use of mefloquine in areas of chloroquine
      resistance. Use of malaria protection measures by travelers to West Africa must
      also be improved.

PMID- 1984540
TI  - Circadian variations in myocardial ischemia. Implications for management.
AB  - Extended ambulatory electrocardiographic monitoring in the patient's customary
      environment provides clear evidence of circadian patterns in myocardial ischemic
      episodes. In patients with effort angina, the highest activity occurs between 6
      AM and noon. This coincides with peaks in diurnal variation of frequency of acute
      myocardial infarction, stroke, and sudden death. A number of potential underlying
      common triggering mechanisms, including catecholamine secretion, sympathetic
      nervous system activity, blood pressure, heart rate, cortisol secretion, and
      aggregability of platelets, exhibit similar surges. As a result of these
      coinciding morning peaks, myocardial oxygen demand is increased and oxygen supply
      reduced after a person arises in the morning. Attention to this vulnerable period
      is merited in the timing and choice of medication, both to prevent or reduce
      ischemia and to modify potential disease-triggering mechanisms.

PMID- 1984541
TI  - NIH consensus conference. Treatment of early-stage breast cancer.

PMID- 1984542
TI  - Prevention of malaria.

PMID- 1984543
TI  - From the Office of the General Counsel. Reports to the National Practitioner Data
      Bank.

PMID- 1984544
TI  - Pathology evaluation of lumpectomy specimen.

PMID- 1984545
TI  - Fat myringoplasty in the guinea pig.
AB  - Fat myringoplasty is a simple office technique for repairing tympanic membrane
      perforations. It involves wedging a piece of fat from the ear lobule into the
      perforation. A search of the literature failed to reveal any controlled studies
      on the efficacy of this method, which may allow patients to avoid more invasive
      procedures. Controlled perforations in guinea pig tympanic membranes were treated
      with fat myringoplasties, paper patches, or no intervention. Four weeks following
      the procedures, ears were examined and photographed under the microscope and
      studied histologically. The fat myringoplasty healing rate exceeded the rates of
      both the control and paper-patch groups. Results were stratified with respect to
      location and size of perforations. The results and histological studies suggest
      that controlled studies in humans are warranted.

PMID- 1984546
TI  - Same-day-stay adenotonsillectomy.

PMID- 1984547
TI  - Magnetic stimulation of the facial nerve.
AB  - Intracranial activation of the facial nerve is now possible with the noninvasive
      techniques of magnetic stimulation. Brief magnetic pulses generated by a coil
      overlying the parietal scalp elicit compound muscle action potentials of similar
      shape and amplitude and greater latency than those produced by
      electroneurography. Mapping studies demonstrate the compound muscle action
      potentials to be of constant latency and varying amplitude with changing coil
      location. Maximum compound muscle action potential amplitudes are obtained with
      the coil center located in a rectangular area superior and posterior to the ear
      canal. A comparison of large and small diameter coils showed them to be equally
      effective for painless facial nerve stimulation; however, the smaller coil
      allowed for a more localized field of activation. Magnetic stimulation has the
      potential to provide cross-the-lesion testing of facial nerve function.

PMID- 1984548
TI  - Magnetic resonance imaging of facial nerve neuromas.
AB  - Facial nerve neuromas are uncommon tumors often confused with other tumors of the
      temporal bone and cerebellopontine angle. Radiologically, it may be impossible to
      differentiate an intracanalicular facial nerve neuroma from an acoustic neuroma.
      We present three case reports of facial nerve neuromas arising within the
      internal auditory canal to show the important magnetic resonance imaging features
      of these tumors. One tumor extended into the cerebellopontine angle, middle
      cranial fossa, and middle ear. Another filled the internal auditory canal and
      extended through the cerebellopontine angle to the brain stem. The third occurred
      in a patient who had neurofibromatosis as well as numerous other intracranial
      tumors. We feel that gadolinium-enhanced magnetic resonance imaging provides the
      most useful information in the preoperative assessment of this disorder.

PMID- 1984549
TI  - Rapid sequence treatment of advanced squamous cell carcinoma of the upper
      aerodigestive tract: a pilot study.
AB  - A review of the literature suggested that prolonged treatment time may lessen the
      probability of cure for patients with advanced squamous cell carcinoma of the
      upper aerodigestive tract. To shorten treatment time, rapid sequence treatment
      (RST) was devised in which chemotherapy, surgery, and irradation were
      administered in a total treatment time of 8 weeks. Twelve patients were treated
      and followed 3 years or longer. Medical complications were minor. Osteonecrosis
      occurred in each of the first five patients and was the only major complication
      of the protocol. Surgical techniques were modified, and no additional patient
      developed osteonecrosis. No patient developed local or regional recurrence. Two
      patients developed distant metastases and three other patients developed second
      primaries. Absolute survival was 50%. Rapid sequence treatment is an aggressive
      and potentially hazardous protocol that yielded encouraging results in this pilot
      study.

PMID- 1984550
TI  - Monothermal differential caloric testing in patients with Meniere's disease.
AB  - The monothermal differential caloric test allows determination of vestibular
      recruitment and decruitment, variables which may help discriminate peripheral
      from central vestibular lesions. Previous reports indicated a strong association
      between vestibular recruitment and Meniere's disease. This study examined
      patients having unilateral Meniere's disease. Nystagmus beat frequency (NBF) and
      slow-component velocity (SCV) responses were recorded by electronystagmography
      (ENG). Electronystagmographic findings showing unilateral dysfunction were
      present in 54% of patients by slow-component velocity and in 31% by nystagmus
      beat frequency. Unilateral hypofunction was the most frequent lateralizing ENG
      finding. Absolute vestibular recruitment occurred in less than 10% of patients
      but relative recruitment was found in nearly 20% of patients. Slow-component
      velocity had higher sensitivity than nystagmus beat frequency, with excellent
      clinical concordance. Monothermal caloric testing as described in this study best
      detects peripheral vestibular disease in Meniere's patients using slow-component
      velocity to determine unilateral hypofunction and relative vestibular
      recruitment.

PMID- 1984551
TI  - Paranasal sinus bony anatomic variations and mucosal abnormalities: CT analysis
      for endoscopic sinus surgery.
AB  - Coronal plane computerized tomographic (CT) scanning has dramatically improved
      the imaging of paranasal sinus anatomy as compared to sinus radiographs.
      Increasingly, subtle bony anatomic variations and mucosal abnormalities of this
      region are being detected. Data regarding the "background" prevalence of these
      findings are needed to determine their clinical relevance. A detailed analysis of
      coronal plane CT scans of the paranasal sinuses obtained in 202 consecutively
      imaged patients was conducted. Special attention was directed toward identifying
      bony anatomic variations and mucosal abnormalities. Anatomic variations studied
      included pneumatization of the middle turbinate, paradoxical curvature of the
      middle turbinate, Haller's cells, and pneumatization of the uncinate process.
      Such bony anatomic variations were detected in 131 (64.9%) of 202 patients and
      were found with a similar frequency in patients scanned for sinus complaints and
      in those scanned for nonsinus reasons. Mucosal abnormalities were detected in 168
      (83.2%) of 202 patients. For those patients scanned during the evaluation of
      sinus-like complaints, mucosal abnormalities were noted in 153 (92.2%) of 166
      cases, and were predominantly detected in the anterior ethmoid region. For
      patients scanned during nonsinus evaluations, mucosal abnormalities were detected
      in 15 (41.7%) of 36 cases, without predilection for the anterior ethmoid region.
      Discussion regarding the prevalence and clinical significance of paranasal sinus
      bony anatomic variations and mucosal abnormalities is included as a guide to
      assist the otolaryngologist and/or radiologist in the evaluation of coronal sinus
      CT scans.

PMID- 1984552
TI  - Extended retrolabyrinthine transtentorial approach to petroclival lesions.
AB  - In this communication, an extension of the retrolabyrinthine approach that has
      permitted safe, effective access to the petrous tip and clivus is presented. The
      basic technique involved complete mastoidectomy, preservation of the middle and
      inner ear structures, removal of the sigmoid and middle fossa plates, middle and
      posterior fossa craniotomies, ligation of the superior petrosal sinus, and
      division of the tentorium. Nine cases that exemplified the versatility of this
      approach constituted the basis of this paper: 2 cholesteatomas, 2 basilar artery
      aneurysms, 2 chordomas, and 3 meningiomas. The indications for, and complications
      of, this method have been discussed.

PMID- 1984553
TI  - Whole-blood filterability in sudden deafness.
AB  - Sixteen patients with sudden deafness (SD), diagnosed on the basis of a battery
      of audiometric tests, but with no other medical or surgical pathology requiring
      drug treatment, underwent monitoring of their hemorheological profiles to see
      whether disturbances in the microcirculation could be linked to SD. Plasma
      viscosity, the filterabilities, (using a low-shear positive pressure system)
      through 5-microns-diameter pore Nuclepore filters, of whole blood and red and
      unfractionated white cells were monitored in 16 SD patients and 32 controls
      matched for age, sex and socioeconomic status. Whole blood filterability and the
      filterability of the red blood cells were significantly impaired in the SD
      patients, which suggests that alterations in the microcirculation are linked, in
      some way, to sudden deafness.

PMID- 1984554
TI  - Comparison of evoked electromyography of the larynx to electrical and magnetic
      stimulation of the motor cortex of the dog.
AB  - The electromyographic and contractile properties of the laryngeal muscles upon
      stimulation of the laryngeal nerve have been described before. In the present
      investigation, we used electrical and magnetic stimulation to activate the
      vocalis muscle in dogs. Stimulation of the vagus nerve at the brain stem exit
      point resulted in evoked vocalis compound muscle action potential identical in
      onset latency and configuration to that obtained by the transcranial single-shock
      magnetic stimulation at high intensity (greater than 80%). Electrical stimulation
      of the laryngeal representation of the somatomotor cortex resulted in a
      contralateral evoked vocalis compound muscle action potential. Central delay time
      for the 10th cranial nerve was calculated by subtracting the latency of the
      vocalis recorded by stimulation of the vagus nerve as it exited the brain stem
      from the latency obtained by direct cortical stimulation.

PMID- 1984555
TI  - Hilger facial nerve stimulator: a 25-year update.
AB  - Percutaneous nerve excitability testing using the Hilger facial nerve stimulator
      was introduced about 25 years ago. The test is reliable, easy to use, and
      inexpensive; it continues to be the most frequently used method for predicting
      prognosis of facial nerve disorders. Between 1966 and 1974, we recorded 10,243
      nerve excitability tests on 865 patients with a mean of 3.29 tests for each
      peripheral branch and 3.43 for the trunk. Using a multiple regression model, we
      determined the effect on nerve stimulation values of age, sex, race, diabetes,
      hypertension, partial or complete clinical paralysis, diagnosis of herpes zoster,
      year of testing, and eventual facial paralysis recovery profile. We discuss
      statistical reliability, provide a table of interpretive results, and offer "tips
      and traps" invaluable to the practitioner. A prospective study of 25 patients
      with residual facial paralysis was evaluated by two separate otolaryngologists to
      determine intertester reliability.

PMID- 1984557
TI  - Soft-tissue premaxillary augmentation flap.

PMID- 1984556
TI  - Catastrophic otologic injury from oral jet irrigation of the external auditory
      canal.
AB  - Jet irrigation is an accepted method for removal of cerumen from the external
      auditory canal. Even at a submaximal power setting, oral jet irrigators can
      generate enough force to rupture the tympanic membrane. Parameters for safe use
      of these irrigators have never been established. Three cases are reported in
      which, in addition to tympanic membrane rupture, oral jet irrigators caused
      ossicular disruption, round and oval window fistulae, and subluxation of the
      stapedial footplate. A prospective study performed on 25 fresh cadavers
      demonstrated a 6% incidence of tympanic membrane perforation when the power
      setting was one-third full power or greater. Recommendations are made for safe
      use of oral jet irrigators for removal of external auditory canal cerumen.

PMID- 1984558
TI  - Nasal approach to the sphenoid sinus after prior septal surgery.

PMID- 1984559
TI  - The pericranial turndown flap for coverage of soft-tissue defects.

PMID- 1984560
TI  - Sternocleidomastoid muscle transfer and superficial musculoaponeurotic system
      plication in the prevention of Frey's syndrome.
AB  - Parotidectomy may be associated with a significant depression in the
      retromandibular region and a significant incidence of gustatory sweating (Frey's
      syndrome). Superiorly and inferiorly based sternocleidomastoid flaps and
      posterior plication of the superficial musculoaponeurotic system were evaluated
      for their ability to ameliorate both consequences. Sixteen patients with
      sternocleidomastoid flaps and 16 patients with superficial musculoaponeurotic
      system plication were compared to a control group of 104 patients. The incidence
      of Frey's syndrome was 47.1% in the control group, 12.5% (P = 0.025) in the
      sternocleidomastoid flap group, and 0% (P = 0.005) in the superficial
      musculoaponeurotic system plication group. The surgical techniques are described.
      The prevalence of Frey's syndrome is discussed with respect to age, sex,
      radiation therapy, and the type of parotidectomy performed. The indications and
      contraindications of the three surgical techniques are described.

PMID- 1984561
TI  - Neurotologic findings in basilar migraine.
AB  - Treatment of a patient with otologic symptoms and associated migraine-like
      headache presents the otolaryngologist with formidable problems. Although
      clinical practice and scientific publications recognize their frequent
      association, relationships have yet to be well defined. This study seeks to add
      order to disarray by delineating symptoms and signs of a clearly identified group
      of migraine patients. Fifty patients with well-defined basilar migraine underwent
      a thorough neurotologic examination, as well as comprehensive auditory and
      vestibular testing. Patients were selected from 5880 patients seen over a 2-year
      period and were prospectively entered into the study after detailed
      questionnaires and testing were completed for each patient. The most common
      symptoms found were dysequilibrium, phonophobia, and head pressure. The most
      common signs were positional nystagmus, low-frequency hearing loss, abnormal
      loudness discomfort level, and an abnormality on caloric examination. Advanced
      vestibular testing showed abnormal amplitude scaling, abnormal toes-down
      pertubation, and an abnormal sway (condition 6) on dynamic posturography. There
      was frequently an asymmetry on computerized rotation. The author concludes that
      the majority of patients have subtle findings on testing, but a few have severe
      peripheral injury due to the basilar migraine. Findings are consistent with the
      theory that basilar migraine is a central nervous system maladaptation syndrome
      which creates otoneurologic symptoms and, in a small percentage of cases, may
      injure the peripheral end-organ.

PMID- 1984562
TI  - Effect of obesity and body fat distribution on sex hormones and insulin in men.
AB  - To investigate the relationship between body fat distribution, sex hormones, and
      hyperinsulinemia in male obesity, we examined 52 obese men (body mass index
      [BMI], 35.0 +/- 6.1, mean +/- SD) and 20 normal-weight controls. Their waist to
      hip circumference ratio (WHR), which was used as an index of fat distribution,
      was 0.985 +/- 0.052 and 0.913 +/- 0.061 (P less than .005), respectively.
      Compared with controls, obese men presented significantly lower levels of total
      (357 +/- 132 v 498 +/- 142 ng/dL; P less than .005) and free testosterone (14.2
      +/- 2.9 v 17.1 +/- 2.6 pg/mL; P less than .05) and sex hormone-binding globulin
      (SHBG; 41.7 +/- 31.9 v 66.2 +/- 18.6 nmol/L; P less than .001) without any
      significant difference on the other sex steroid or on gonadotropin
      concentrations. Fasting and glucose-stimulated insulin and C-peptide levels were
      significantly higher in obese than in controls, and in obese with the WHR value
      greater than 0.97 (corresponding to the distribution median) than in those with
      WHR lower or equal to 0.97. BMI was negatively correlated with testosterone (P
      less than .005), free testosterone (P less than .01), and SHBG (P less than .001)
      and positively with fasting (P less than .001) and glucose-stimulated (P less
      than .005) C-peptide concentrations, whereas no relationship was found between
      these variables and WHR values. On the contrary, WHR was significantly correlated
      with fasting and post-glucose insulin levels (P less than .05), but not with
      those of sex steroids.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1984563
TI  - Biochemical abnormalities in the heart of rats fed a sucrose-rich diet: is the
      low activity of the pyruvate dehydrogenase complex a result of increased fatty
      acid oxidation?
AB  - We have previously shown that normal Wistar rats fed for 3 weeks with an
      isocaloric sucrose-rich (63%) diet (SRD) develop high levels of plasma free fatty
      acids and increased triacylglycerol content in the myocardium. We are now
      reporting that these changes are accompanied by remarkably low levels of the
      active form of the pyruvate dehydrogenase complex (PDHa; mean +/- SEM, 37.2% +/-
      3.7% of the total activity) when compared with levels found in hearts donated by
      control rats fed the standard chow diet (STD; 71.0% +/- 2.8%; P less than .01).
      Increased concentrations of both long-chain acyl-CoA (0.21 +/- 0.03 v 0.06 +/-
      0.01 mumol.g dry weight-1 found in STD; P less than .01) and acetyl-CoA (0.17 +/-
      0.05 v 0.09 +/- 0.01 found in STD; P less than .01), as well as a relative
      decrease in coenzyme A (CoASH) (0.21 +/- 0.02 v 0.32 +/- 0.05 from STD; P = NS),
      resulting in an increased acetyl-CoA/CoASH ratio (0.80 +/- 0.13 v 0.29 +/- 0.03
      in STD; P less than .01) may have stimulated the PDH kinase, leading in turn to
      an inactivation of the PDH complex. The above enzymatic and metabolic changes in
      the in situ heart of SRD-fed rats were still present after perfusing them for 35
      minutes with a Krebs-Henseleit buffer containing 11 mmol/L glucose as the only
      exogenous substrate.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1984564
TI  - Calcitonin stimulates 1,25-dihydroxyvitamin D production in diabetic rat kidney.
AB  - In diabetic animals, there is a decrease in serum 1,25-dihydroxyvitamin D
      [1,25(OH)2D] and in renal production of 1,25(OH)2D. In nondiabetic animals, renal
      1,25(OH)2D production is markedly stimulated by parathyroid hormone (PTH) and
      calcitonin (CT). There is evidence that diabetes impairs the responsiveness of
      the kidney to PTH. The effect of diabetes on responsiveness to CT is unknown. The
      studies reported here determined the effect of streptozotocin-induced diabetes on
      renal responsiveness to PTH and CT. Experiments were performed in 7- to 8-week
      old rats that were fed a diet sufficient in calcium and vitamin D and were
      thyroparathyroidectomized (TPTX) 5 days before hormone treatment. PTH (0.33 U/g
      body weight at 24, 12, and 2 hours before death) significantly increased renal
      1,25(OH)2D production by threefold in nondiabetic rats. This effect was markedly
      attenuated by diabetes. On the other hand, CT (20 U/100 g body weight at 12 and 2
      hours before death) produced a maximal response in both groups of animals. In
      diabetic rats, CT stimulated renal 1,25(OH)2D production fivefold, whereas PTH
      stimulated production only 1.5-fold. Diabetes did not affect the capacity of PTH
      to increase serum calcium or decrease renal tubular reabsorption of phosphorus
      (TRP). These findings suggest that the decrease in renal 1,25(OH)2D production
      seen in experimental diabetes may be due to decreased renal responsiveness to
      PTH, but not to decreased responsiveness to CT.

PMID- 1984565
TI  - Isolation of nascent high-density lipoprotein from rat liver perfusates by
      immunoaffinity chromatography: effects of oleic acid infusion.
AB  - Immunoaffinity chromatography on a column of rabbit IgG anti-rat apolipoprotein
      (apo) A-I covalently bonded to agarose was used to isolate nascent high-density
      lipoprotein (nHDL) from recirculated perfusates of rat livers. After passage
      through the affinity column, the bound material was eluted with sodium
      thiocyanate and analyzed for apolipoproteins and lipids. The protein content was
      52% and the lipid composition was 37% triglyceride, 40% phospholipid, and 23%
      cholesterol. Apolipoproteins E and A-I each comprised approximately one third of
      the total, and very little apo B was detectable as judged by SDS-PAGE analysis.
      The affinity-isolated particles were therefore similar in composition to the
      major apo A-I:apo E-rich subfraction of nHDL isolated by ultracentrifugation in
      earlier work. It is concluded that the apo E in this class of nHDL (containing
      both apo E and apo A-I) is present in the secreted particle and is not a
      consequence of a loss of apo E from very-low-density lipoprotein (VLDL) during
      ultracentrifugation. The high triglyceride content in the virtual absence of apo
      B confirms and extends previous analyses and reinforces the conclusion that nHDL
      particles are enriched in triglyceride compared to plasma HDL. The inclusion of
      4% albumin in the perfusion medium did not significantly change the total
      triglyceride output of 115 micrograms/g liver/h, but it decreased the
      triglyceride output isolated by anti-apo A-I affinity chromatography from 3.2 to
      0.48 micrograms/g liver/h. The addition of oleic acid complexed to albumin
      increased the total triglyceride output by 70% and that associated with the
      immunoaffinity column increased from 0.48 to 2.7 micrograms/g liver/h.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1984566
TI  - Responses of growth hormone and cortisol to intravenous glucose loading test in
      patients with anorexia nervosa.
AB  - The hypothalamic satiety and hunger centers appear to be affected by changes in
      circulating blood glucose concentrations. The response of the centers, in turn,
      is reflected by alterations in growth hormone (GH) and cortisol levels. There are
      no studies attempting to relate blood glucose and GH and cortisol changes in
      patients with anorexia nervosa (AN) during an intravenous glucose tolerance test
      (IVGTT). In the present inquiry, IVGTT (10 g) were performed on AN patients to
      characterize the satiety and hunger centers' responses to changes in glucose and
      insulin levels as reflected by GH and cortisol levels. Study participants were 15
      female AN patients and eight healthy female volunteers. No significant
      differences in blood glucose levels were observed between the two groups.
      However, immunoreactive insulin (IRI) levels in AN patients were significantly
      lower than those in the control group. Although GH and cortisol concentrations
      were significantly suppressed after the infusion in the control group, the AN
      patients' GH levels paradoxically increased, and cortisol levels did not change.
      Moreover, a negative correlation was observed between delta GH and delta IRI in
      all individuals in this study (r = -.61, P less than .01). In conclusion,
      abnormal GH and cortisol responses to a 10-g IVGTT were found in patients with
      AN. delta GH levels correlated negatively with delta IRI levels. These data
      suggest that hypothalamic satiety and hunger centers in AN respond abnormally to
      change in blood glucose levels.

PMID- 1984567
TI  - Hypolipidemic effect and mechanism of ketoconazole without and with
      cholestyramine in familial hypercholesterolemia.
AB  - The hypocholesterolemic and metabolic effects of ketoconazole (400 mg/d) alone
      (inhibits cholesterol synthesis at 14 alpha-demethylation of lanosterol) and in
      combination with cholestyramine (12 g/d), were studied in nine women with
      xanthomatous familial hypercholesterolemia (FH). In addition to serum lipoprotein
      levels, cholesterol precursors, fecal steroids, and cholesterol absorption were
      measured before and during the drug treatments. Serum total and low-density
      lipoprotein (LDL)-cholesterol were reduced by 19% and 22% with ketoconazole; the
      respective changes were 16% and 21% for cholestyramine, and 31% and 41% for the
      combined ketoconazole and cholestyramine treatment. Serum triglycerides, very-low
      density lipoprotein (VLDL)-and high-density lipoprotein (HDL)-cholesterol levels
      were unchanged. Accumulation of cholesterol precursors in serum suggested that
      ketoconazole inhibited cholesterol synthesis at delta 8-sterol levels. Serum and
      fecal lanosterols were increased up to 20-fold and were interrelated. Their
      maximal serum level was 1.3 mg/DL and the lanosterol contents were negatively
      related to the serum cholesterol levels. The intestinal absorption and total
      intestinal fluxes of cholesterol were reduced by 27% and 29%. Cholesterol and
      bile acid synthesis were decreased by ketoconazole only when combined with
      cholestyramine. The synthesis of chenodeoxycholic acid was deeply hindered by
      ketoconazole. Thus, ketoconazole efficiently lowers serum total and LDL
      cholesterol levels in FH patients, probably by inhibiting cholesterol synthesis
      and absorption. Effective biliary and fecal outputs of cholesterol precursors
      prevent their excessive increase in serum.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1984568
TI  - A modified minimal model analysis of insulin sensitivity and glucose-mediated
      glucose disposal in insulin-dependent diabetes.
AB  - Although glucose utilization is impaired in insulin-dependent diabetes mellitus
      (IDDM), it is unclear whether this is due to reductions in insulin sensitivity
      (Si) and/or glucose-mediated glucose disposal (SG). The minimal model of Bergman
      et al can be applied to a frequently sampled intravenous glucose tolerance test
      (FSIGT) to simultaneously estimate Sl and SG, but cannot accommodate data from
      diabetics. Exogenous insulin approximating the normal pattern of insulin
      secretion was infused during FSIGTs in eight young non-obese C-peptide-negative
      IDDM subjects, but with the total dose modified to achieve sufficient glucose
      disappearance rates (KG) to allow analysis of data. The minimal model was
      modified to model the effects of the exogenous insulin on glucose kinetics to
      estimate SI and SG. Despite deliberately achieving supranormal plasma-free
      insulin levels during the FSIGT ("first-phase insulin" = 62 +/- 9 SE mU/L;
      "second phase insulin" = 34 +/- 9 mU/L), the diabetics showed low-normal KG
      values (1.3 +/- 0.29 min-1 X 10(2). Using the model, good parameter resolution
      (fractional SD [FSD] less than .5) was achieved (IDDM v controls: SI = 2.5 +/-
      0.6 v 8.3 +/- 1.5 min-1.mU-1.L-1 X 10(4); SG = 1.6 +/- 0.5 v 2.6 +/- 0.2 min-1 X
      10(2); P less than .05). This reduction in SG was confirmed in the same IDDM
      subjects by FSIGT during basal insulin infusion only (SG = 1.0 +/- 0.3 min-1 X
      10(2)).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1984569
TI  - Glutamine metabolism after small intestinal resection in humans.
AB  - Glutamine and leucine kinetics were measured using stable isotopes in five
      enterectomized patients (residual small bowel, 80 +/- 25 cm [mean +/- SE]) who
      were in a near normal nutritional status at distance from surgery. While
      parameters of leucine metabolism were normal, rates of whole body glutamine
      utilization were reduced by 20% in the patients. The data suggest that the small
      intestine plays a prominent role in glutamine utilization in vivo in humans.

PMID- 1984570
TI  - Apolipoprotein C-II and C-III metabolism in a kindred of familial
      hypobetalipoproteinemia.
AB  - Three affected members of a kindred with asymptomatic hypobetalipoproteinemia
      (HBL) showed low levels of triglycerides, low-density lipoprotein (LDL)
      cholesterol, and apolipoproteins (apo) B, C-II, and C-III. Turnover of iodine
      labeled apo C-II and apo C-III associated in vitro to plasma lipoproteins was
      studied after intravenous injection. Radioactivity in plasma and lipoproteins
      (95% recovered in high-density lipoprotein [HDL] density range) and in 24-hour
      urine samples was observed for 16 days. A parallelism of the slowest slopes of
      plasma decay curves was observed between apo C-II and apo C-III, indicating a
      partial common catabolic route. Urine/plasma radioactivity ratio (U/P) varied
      with time, suggesting heterogeneity of metabolic pathways. A new compartmental
      model using the SAAM program was built, not only fitting simultaneously plasma
      and urine data, but also taking into account the partial common metabolism of
      lipoprotein particles (LP) containing apo C-II and apo C-III. The low apo C-II
      and C-III plasma concentrations observed in HBL compared with normal resulted
      from both an increased catabolism and a reduced synthesis, these changes being
      more marked for apo C-III. The modifications in the rate constants of the
      different pathways calculated from the new model are in favor of an increased
      direct removal of particles following the fast pathway, likely in the very-low
      density lipoprotein (VLDL) density range.

PMID- 1984571
TI  - Differential effects of insulin resistance on leucine and glucose kinetics in
      obesity.
AB  - The effects of insulin resistance on glucose and amino acid metabolism were
      studied in obese nondiabetic women (body mass index [BMI], (32.8 +/- 2) and in
      lean controls. Glucose disposal rate, hepatic glucose production, and leucine
      carbon flux and oxidation were simultaneously measured during the postabsorptive
      state and during euglycemic hyperinsulinemia, by means of primed, constant
      infusions of D-[6,6-2H2]glucose and L-[1-13C]leucine. Each subject participated
      in two insulin clamp studies on separate days, at infusion rates of 10 and 40 mU
      (m2.min)-1, producing plasma insulin levels of 20 to 25 and 70 to 80 microU/mL,
      respectively. Fat-free mass (FFM) was calculated from underwater weighing
      measurements. Insulin-mediated glucose disposal rate was significantly slower in
      the obese group: 2.05 +/- 0.05 versus 3.84 +/- 0.18 mg (kg.min)-1 in controls
      during the 10-mU insulin clamp, and 3.80 +/- 0.23 versus 9.16 +/- 0.47 mg
      (kg.min)-1 during the 40-mU clamp. The insulin-induced decrease in plasma levels
      of branched chain amino acids was also significantly blunted in the obese group.
      Baseline leucine flux was similar in lean and obese subjects (78 +/- 3 and 71 +/-
      2 mumol (kg.h)-1, respectively), and its decline in response to insulin infusion
      was also comparable (8% and 10% during the 10-mU/m2 clamp, and of 17% and 18%
      during the 40-mU/m2 clamp in lean and obese, respectively). Basal leucine carbon
      oxidation (from [13C]leucine and [13C]alpha ketoisocaproate [alpha-KIC] plasma
      enrichments) was also similar in lean and obese, and did not change significantly
      with insulin infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1984573
TI  - Effects of small changes in glucagon on glucose production during a euglycemic,
      hyperinsulinemic clamp.
AB  - The aim of this study was to examine the influence of small changes in glucagon
      on hepatic glucose production during a euglycemic, hyperinsulinemic clamp. During
      1.0 mU/kg.min insulin infusion, euglycemia was maintained by glucose infusion and
      glucagon was infused at various rates so as to cause plasma glucagon levels to
      increase, decrease, or remain unchanged. Changes in glucagon were found to be
      positively associated with changes in glucose production and inversely related to
      the degree of suppression of tracer or arteriovenous difference determined
      endogenous glucose production. Thus, animals in which the glucagon levels
      increased, appeared to have decreased hepatic insulin sensitivity, while animals
      in which glucagon levels decreased, appeared to have increased insulin
      sensitivity. In conclusion, since glucagon often declines during a euglycemic
      hyperinsulinemic clamp, and since small changes in glucagon can have marked
      effects on the suppression of hepatic glucose output even in the presence of high
      insulin levels, changes in glucagon should be considered when conclusions
      regarding hepatic insulin sensitivity are being drawn.

PMID- 1984572
TI  - The effects of euglycemic hyperinsulinemia and amino acid infusion on regional
      and whole body glucose disposal in man.
AB  - We investigated the effects of amino acid infusion on regional and whole body
      glucose metabolism in 16 normal volunteers, age 32 to 70 years. Ten subjects
      underwent 140-minute euglycemic insulin infusions at the rate of 1 mU/kg.min with
      concomitant 10% amino acid infusion. Six volunteers who underwent identical
      euglycemic insulin infusions without amino acid infusion served as controls.
      Whole body glucose disposal was estimated by the rate of exogenous glucose
      infusion required to maintain euglycemia, and peripheral glucose balance was
      evaluated by the forearm balance technique. In four subjects from each group, a
      primed, continuous infusion of [3-3H]glucose was used to quantify endogenous
      glucose production (EGP). Comparable states of hyperinsulinemia were achieved
      with insulin concentrations (microU/mL) of 101 +/- 7 observed in the group with
      amino acid infusion and 95 +/- 14 in the control group. Whole body glucose
      utilization was significantly lower (P less than .001) in the subjects receiving
      amino acid infusion (5.0 +/- 0.4 mg/kg.min) compared with the control group (8.7
      +/- 0.8 mg/kg.min). Forearm glucose disposal was markedly reduced (P less than
      .05) in the group receiving amino acid infusion (1,385 +/- 330 nmol/100 g.min)
      compared with controls (2,980 +/- 460 nmol/100 g.min). Under comparable
      conditions of euglycemia and hyperinsulinemia, virtually complete suppression of
      EGP was observed in both groups. We conclude that infusion of amino acids with
      insulin under euglycemic conditions reduces whole body glucose utilization
      primarily by reducing peripheral glucose disposal.

PMID- 1984574
TI  - Vitamin C and vitamin E status in the spontaneously diabetic BB rat before the
      onset of diabetes.
AB  - Ascorbic acid (AA), dehydroascorbic acid (DHAA), and vitamin E were measured in
      tissues and plasma of 30 control and 30 spontaneously diabetic BioBreeding rats
      (BBdp) during development and before the onset of diabetes. At weaning, rats were
      fed an AIN-76 semisynthetic diet for 30, 64, or 113 days, after which plasma and
      tissues from 10 rats of each group were collected and analysed for AA, DHAA, and
      vitamin E. AA and DHAA levels were significantly increased in plasma and spleen
      of the diabetes-prone rats compared with those of the control group at 30 and 64
      days, but the difference disappeared by 113 days. No differences were observed in
      liver, adrenals, thymus, and pancreas at any of the time periods. However, lower
      levels of vitamin E were observed in adrenal gland, thymus, and pancreas of the
      diabetes-prone rats. It is concluded that BBdp rats have an altered metabolism of
      AA, DHAA, and vitamin E, before the onset of diabetes. These changes could be due
      to genetic and physiological factors operating during development of this rat
      strain.

PMID- 1984575
TI  - Antioxidant enzyme activity during prolonged exercise in amenorrheic and
      eumenorrheic athletes.
AB  - Exogenous 17 beta-estradiol (E2) has been shown to be associated with elevated
      levels of erythrocyte glutathione peroxidase (GPX) activity. The purpose of this
      study was to examine the influence of endogenous E2, as defined by menstrual
      status (amenorrhea v eumenorrhea), on activity of blood antioxidant enzymes at
      rest and during prolonged exercise. Six amenorrheic (AMc) and six eumenorrheic
      (EUc) athletes were subjected to a treadmill running test at 60% VO2max for 90
      minutes. Serial blood samples were taken from a forearm vein at rest, 30, 60, and
      90 minutes during exercise, and 15 minutes into recovery. Resting estrogen levels
      were significantly lower in AMc athletes at rest and during exercise as compared
      with EUc athletes, whereas plasma cortisol levels in AMc were significantly
      higher. GPX activity was significantly higher in AMc than EUc at rest (46.9 +/-
      7.7 v 30.2 +/- 2.2 nmol/min x mg Hb, P less than .05, respectively) and
      throughout exercise. Glutathione reductase (GR) activity was similar between the
      two groups at rest and was significantly higher (P less than .01) in AMc than EUc
      during exercise. Plasma lipid peroxidation and catalase activity did not change
      significantly in response to exercise, nor were they different between AMc and
      EUc athletes. GPX activity was found to be negatively correlated with E2 (r = 
      .64, P less than .01) and positively correlated with cortisol (r = .69, P less
      than .01). It is tentatively concluded that the alteration of hormonal status in
      amenorrhea has an influence on the blood antioxidant enzyme system.

PMID- 1984576
TI  - Metabolic regulation of plasma apolipoprotein E by estrogen and progesterone in
      the baboon (Papio sp).
AB  - Apolipoprotein (apo) E plays an important role in the metabolism of lipoproteins.
      To determine the effects of estrogen and progesterone on plasma levels and
      metabolism of apo E, we used 12 ovariectomized baboons fed a cholesterol- and fat
      enriched diet. These baboons were divided into four groups and treated with
      estrogen, progesterone, estrogen + progesterone, and a placebo control. After 10
      months, although the lipid levels were not different among the treatment groups,
      low-density lipoprotein (LDL)/high-density lipoprotein (HDL) ratios in the
      estrogen + progesterone group were significantly lower than those in the control
      and progesterone groups. Estrogen alone or in combination with progesterone
      decreased plasma apo E levels significantly compared with those in the control
      group. Plasma apo E levels in the progesterone group were similar to those in the
      control group. In all groups, most (greater than 60%) of the apo E was present in
      HDL. HDL apo E concentrations in the estrogen and estrogen + progesterone groups
      were significantly lower than those in the control and progesterone groups. To
      determine the metabolic mechanisms of these changes in apo E levels, turnover
      studies were conducted by injection of iodinated apo E-labeled very-low-density
      lipoprotein (VLDL) and HDL. Residence times were calculated using
      multicompartment modeling. Progesterone alone and in combination with estrogen
      decreased residence times of apo E injected in both HDL and VLDL compared with
      estrogen alone and control groups. Progesterone alone also increased the apo E
      production rate compared with other groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1984577
TI  - Asthma deaths: where now?

PMID- 1984578
TI  - Habitual physical activity and cardiovascular risk factors.
AB  - The relationships between different levels of participation in physical activity
      and biological indices of cardiovascular risk were examined in a sample of 6814
      male and female adults who took part in a national risk factor prevalence survey.
      Participation in physical activity was classified as "aerobic" (14.6% of total),
      "moderate" (53.6%) or "inactive" (31.8%). Bivariate analyses found significant
      associations between level of exercise participation and diastolic blood
      pressures in men, but not in women; significant associations were found between
      reported physical activity and systolic blood pressure, total serum cholesterol,
      high-density lipoprotein (HDL) cholesterol, HDL/total cholesterol ratio and
      triglycerides for both men and women. Further analyses were controlled for age,
      education, and the survey site, which were potential confounders of the
      association between physical activity and other coronary heart disease risk
      factors. After adjustment, significant associations remained between levels of
      exercise participation and HDL cholesterol level, HDL/total cholesterol ratio and
      serum triglyceride levels for both sexes. In women, there was also a significant
      relationship between activity level and body mass index. In addition, for men
      only, there was a significant inverse relationship between physical activity and
      total cholesterol, and, for older men, between physical activity and systolic
      blood pressure. It is well recognised that physical activity has an independent
      effect on reducing the risk of coronary heart disease. The results of this study
      suggest that there may be small supplementary effects mediated through the
      relationship between exercise and other biological cardiovascular risk factors.

PMID- 1984579
TI  - General practice in the nineties: cottage industry or academic specialty?

PMID- 1984580
TI  - DNA diagnostic tests: expanding role and evolving techniques.

PMID- 1984581
TI  - Principles behind practice. Introduction to clinical epidemiology.

PMID- 1984582
TI  - Prison doctor.

PMID- 1984583
TI  - Marital problems and their presentation.
AB  - Marital problems are inevitable and are, in general, related to the spouses'
      personalities and their relationship; their presentations are protean,
      particularly with psychosomatic illness and unusual illness in children.

PMID- 1984584
TI  - Behaviour disorders in children.

PMID- 1984585
TI  - How to score opiates.

PMID- 1984586
TI  - Venous ulceration: factors influencing recurrence after standard surgical
      procedures.
AB  - Ninety patients with chronic venous ulceration were investigated to determine the
      extent of the incompetence of the venous valves. They were then treated by
      established surgical methods to control reflux. All wore fitted compression
      stockings and were regularly followed up. Forty-two patients had valvular
      incompetence confined to the perforating and superficial veins. All their ulcers
      healed and only one developed a minor recurrence during the three year follow-up.
      Nineteen patients had additional but limited incompetence of the deep veins; all
      their ulcers healed, but three developed a recurrence. Twenty-nine patients had
      extensive deep vein valvular incompetence including incompetence of the popliteal
      valve; in 12 of these patients either the ulcer failed to heal or the patient
      developed a recurrent ulcer within 18 months. Thirty-two other patients developed
      further venous reflux from the opening of new channels, including the perforating
      veins of the foot, and required sclerosants or local ligation. It was concluded
      that established surgical techniques, thoroughly performed, were very effective
      for the treatment of chronic venous ulceration provided the popliteal valves were
      competent. When the popliteal valves were incompetent the recurrence rate was
      unacceptably high and additional methods, including vein valve transplants,
      excision of the ulcer with skin grafting and lumbar sympathectomy, were
      considered. Nine of 11 patients who received a vein valve transplant had falls in
      their ambulant venous pressures, improvement in the nutrition of their skin and
      healing of their recurrent ulcers.

PMID- 1984587
TI  - Treatment of acute organophosphate poisoning.
AB  - The biochemistry and pharmacology of poisoning by organophosphorus esters and
      carbamates are outlined and methods of diagnosis and treatment are discussed.
      Treatment consists of reduction of exposure by decontamination, induction of
      vomiting or gastric lavage; pharmacological treatment with atropine and oximes
      (pralidoxime and obidoxime); and supportive treatment with artificial respiration
      and centrally acting drugs such as diazepam. The sequence of treatment depends
      solely on the severity of poisoning.

PMID- 1984588
TI  - All that wheezes is not asthma. An unusual case of airways obstruction.

PMID- 1984589
TI  - Listeria monocytogenes peritonitis associated with CAPD.
AB  - Listeria monocytogenes peritonitis developed in a 67-year-old man on continuous
      ambulatory peritoneal dialysis following a catered luncheon. Alcoholic liver
      disease was a predisposing factor. L. monocytogenes multiplies at 4 degrees C. It
      is often present in imported soft cheese, less often in chicken and other
      refrigerated food. Listeria peritonitis has not been previously reported in
      Australia.

PMID- 1984590
TI  - AIDS, the law and civil liberties.
AB  - In dealing with HIV infection and AIDS, the law must balance the public health
      interests of the community against the potentially conflicting rights of
      individuals to liberty and privacy. This article reviews public health
      legislation currently in force in Australian States and Territories, discusses
      the potential for coercive strategies to be applied to AIDS sufferers and persons
      who are or who are presumed to be infected with HIV, and considers how to deal
      with HIV-infected persons who knowingly or recklessly spread the virus. It is
      possible that strong measures to control the spread of HIV may be
      counterproductive because they discourage the cooperation of infected persons and
      groups at high risk of infection. Although the potential for restrictive
      practices is great, the law must make, and in Australia has made, some
      compromises in the interests of the individual and the larger community.

PMID- 1984591
TI  - Swallowing disorders in stroke.

PMID- 1984592
TI  - Maintaining specialist services.

PMID- 1984594
TI  - Comparison of standard intravenous cannulas and a new needle-stick-safe cannula
      in the emergency department.

PMID- 1984593
TI  - Mapping brain genes.

PMID- 1984595
TI  - Divers' Emergency Service.

PMID- 1984596
TI  - Eosinophilic enteritis in the Northern Territory.

PMID- 1984597
TI  - Weight reduction and epilepsy.

PMID- 1984599
TI  - Asthma triage.

PMID- 1984598
TI  - Eosinophilia-myalgia syndrome associated with L-tryptophan use.

PMID- 1984600
TI  - Child sexual abuse.

PMID- 1984601
TI  - Choice of cholesterol-lowering drugs.

PMID- 1984602
TI  - Why we need a national child health policy.
AB  - Although the federal government has long had an interest in the health of
      children, action in support of this interest has been limited, fragmented, and
      inequitable. While health problems are increasing and becoming more complex and
      while policy leaders, business groups, and the public recognize that action is
      necessary, no response has been forthcoming. Development of a policy with
      measurable goals is needed. Resources must be allocated and data collected to
      periodically evaluate progress toward goals and to appropriately redirect
      resources.

PMID- 1984603
TI  - Surfactant treatment of full-term newborns with respiratory failure.
AB  - Surfactant inactivation has been shown to be a significant factor in animal
      models of lung injury and may also be important in some forms of respiratory
      failure in full-term newborns. Fourteen full-term newborns with respiratory
      failure associated with pneumonia (7 patients) and meconium aspiration syndrome
      (7 patients) were treated with 90 mg/kg of a calf lung surfactant extract, given
      intratracheally up to every 6 hours for a maximum of four doses. The group mean
      fraction of inspired oxygen (FI02) before treatment was 0.99 +/- 0.01 SEM, and
      the mean airway pressure (MAP) was 14.6 +/- 1.0 cm H2O. Patients showed
      significant improvement in oxygenation after initial surfactant treatment, with
      the arterial-alveolar oxygenation ratio (a/A ratio) rising from 0.09 +/- 0.01
      before surfactant treatment to 0.22 +/- 0.05 by 15 minutes (P = .03) and
      remaining improved for 6 hours. The oxygenation index, incorporating MAP as well
      as oxygen variables, also improved significantly from 26.2 +/- 3.1 to 11.2 +/-
      1.7 at 15 minutes (P less than .001), with improvement sustained for more than 6
      hours. Chest radiographs were blindly scored from 0 (normal) to 5 (severe
      opacification), and these improved with marginal significance after initial
      surfactant treatment (from 2.9 +/- 0.2 to 2.5 +/- 0.2, P = .05).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1984604
TI  - Safe handling of vaccines.

PMID- 1984605
TI  - Does nasogastric tube cause pulmonary aspiration in children?

PMID- 1984606
TI  - Obtaining a seal with otic specula: must we rely on an air of uncertainty?

PMID- 1984608
TI  - American Academy of Pediatrics Committee on Injury and Poison Prevention and
      Committee on Fetus and Newborn: Safe transportation of premature infants.

PMID- 1984607
TI  - American Academy of Pediatrics Committee on School Health. Medical guidelines for
      day camps and residential camps.
AB  - Because camp programs differ in many ways, especially in scheduled activities,
      availability of skilled medical support for the health care staff, and
      environmental conditions, camp administrators should use the medical guidelines
      provided in this statement to develop camp-specific protocols for day and
      residential camps.

PMID- 1984609
TI  - Little help from article on anabolic steroids.

PMID- 1984610
TI  - Tetracycline for Rocky Mountain spotted fever.

PMID- 1984611
TI  - Ibuprofen for fever.

PMID- 1984612
TI  - More on sports deficit disorder.

PMID- 1984613
TI  - Bismuth subsalicylate in the treatment of acute diarrhea in children: a clinical
      study.
AB  - Bismuth subsalicylate (BSS) and placebo were evaluated in a double-blind, placebo
      controlled study as adjunct to rehydration therapy in 123 children, aged 4 to 28
      months, hospitalized with acute diarrhea. The dosing regimen was 20 mg/kg five
      times daily for 5 days. Significant benefits were noted in the BSS group compared
      with placebo as manifested by decreases in stool frequency and stool weights and
      an improvement in stool consistency, significant improvement in clinical well
      being, and shortening of the disease duration. Patients treated with BSS had a
      significant reduction in duration of hospital stay (6.9 days) compared with
      placebo-treated patients (8.5 days). Also, intravenous fluid requirements
      decreased significantly more rapidly and to a greater degree in the BSS-treated
      group. Bismuth subsalicylate was associated with clearance of pathogenic
      Escherichia coli from the stools in 100% of cases but was not different from
      placebo in rotavirus elimination. Bismuth subsalicylate was well tolerated with
      no reported adverse effects. Blood bismuth and serum salicylate levels were well
      below levels considered toxic. In this study, BSS provided effective adjunctive
      therapy for acute diarrhea, allowing children to get well sooner with less demand
      on the nursing and hospital staff.

PMID- 1984614
TI  - Use and misuse of oral therapy for diarrhea: comparison of US practices with
      American Academy of Pediatrics recommendations.
AB  - To determine how closely US pediatricians follow the 1985 American Academy of
      Pediatrics Committee on Nutrition's recommendations on oral therapy for acute
      diarrhea, a questionnaire was administered to four groups: New England private
      practitioners, pediatricians from 27 states attending a postgraduate course,
      representatives of departments of pediatrics at US schools of medicine, and
      housestaff at Boston Children's and Massachusetts General hospitals. The
      responses from departments of pediatrics and housestaff were not significantly
      different from those of community practitioners in most categories. The reported
      rate of use of glucose-electrolyte solutions recommended by the American Academy
      of Pediatrics was not different from the use of nonphysiologic, high-osmolar, low
      salt solutions such as sodas and juices. The usage rate for glucose-electrolyte
      solutions meeting the American Academy of Pediatrics-recommended carbohydrate-to
      sodium ratio of less than 2:1 was less than 30%. Other findings included the
      general lack of agreement on the use of a single type of therapy and the common
      use of oral therapy only for mild or no dehydration. Although the American
      Academy of Pediatrics recommends that feeding be reintroduced in the first 24
      hours of a diarrheal episode, the majority of respondents withhold feeding until
      the second day or later. These findings indicate that educational programs on
      oral therapy during acute diarrhea are needed in the United States.

PMID- 1984615
TI  - Infrared thermometry of newborn infants.
AB  - An infrared thermometer, the FirstTemp, was tested among newborn infants by
      comparing tympanic membrane temperature measurements in three operating modes,
      "Cal-tympanic," "Cal-surface," and "Cor-tympanic," with nearly simultaneous
      tympanic membrane, rectal, and axillary temperature measurements using other
      standard methods. The FirstTemp underestimated other measurements of body
      temperature in the "Cal-tympanic" mode and overestimated them in the "Cor
      tympanic" mode. In the "Cal-surface" mode, the First-Temp readings were
      significantly lower than tympanic membrane temperatures measured with a
      thermistor probe and electronic thermometer (mean difference 0.2 degrees C) but
      not significantly different from rectal or axillary temperatures. According to
      these results, the FirstTemp can be used reliably in the "Cal-surface" mode but
      not in the "Cal-tympanic" or "Cor-tympanic" mode. Its speed and ease of operation
      offer significant advantages over traditional clinical methods of temperature
      measurement.

PMID- 1984616
TI  - Stridor: intracranial pathology causing postextubation vocal cord paralysis.
AB  - During an 18-month period in a pediatric intensive care unit, nine patients with
      vocal cord paralysis were identified using flexible bronchoscopy. When tracheally
      extubated, each child was found to have stridor. The children ranged in age from
      17 days to 5 1/2 years. Two patients had unilateral paralysis, but neither
      required tracheostomy. Seven patients displayed bilateral abductor vocal cord
      paralysis. Of these, six patients required tracheostomy. Surgical injury to the
      recurrent laryngeal nerve was the probable cause in two patients. The other seven
      patients had neurologic disorders with documented or suspected increases of
      intracranial pressure. Four of the seven patients with bilateral abductor vocal
      cord paralysis regained cord mobility within 4 months. Both children with
      unilateral cord paralysis have no stridor and vocalize well 1 year later. Cord
      paralysis in the setting of intracranial hypertension probably results from
      compression or ischemia of the vagus nerve before it exits the skull. Early
      visualization of the larynx should be done in patients who become stridulous when
      extubated, especially those with prior thoracic procedures or with neurologic
      disorders associated with intracranial hypertension.

PMID- 1984617
TI  - A new system for location of endotracheal tube in preterm and term neonates.
AB  - A randomized, controlled trial was conducted to evaluate a new noninvasive system
      for placement of the endotracheal tube, based on a magnetic field interference
      sensing technique. Seventy-two neonates treated by the standard technique were
      compared with 70 treated by the new system (TRACH MATE), with radiographic
      localization as the standard. As judged by the author(s) on the morning after the
      intubation, correct initial placement was achieved in 69 (78%) of 88 intubations
      using the new system, compared with 71 (66%) of 107 using the standard technique
      (Fisher's Test, one-tailed, P = .044). Repositioning was actually done in 23
      (26%) of 88 TRACH MATE intubations, compared with 42 (39%) of 107 standard
      intubations (Fisher's test, one-tailed; P = .037). Intubation of the right main
      bronchus occurred in 7 standard intubations, but in none of the TRACH MATE
      intubations (Fisher's test, one-tailed; P = .014). Endotracheal tube position
      (high, low, or appropriate) was correctly determined by TRACH MATE in 77 (90%) of
      85 intubations; the position was not recorded on three occasions. No differences
      in the number of complications (eg, unplanned extubations, distal displacement,
      subglottic stenosis) were found between the two groups. It is concluded that the
      TRACH MATE technique is superior to the standard clinical method in initial
      placement of the endotracheal tube.

PMID- 1984618
TI  - Bacteremia with otitis media.
AB  - To investigate the occurrence and outcome of bacteremia associated with otitis
      media, charts were reviewed from patients who were 3 to 36 months of age, had
      temperatures greater than or equal to 39 degrees C, and were diagnosed with
      isolated clinical otitis media. A total of 2982 patients were identified. Blood
      cultures were obtained from 1666 (56%). Of the 1666 patients, who had blood drawn
      for cultures, 50 (3.0%) had bacteremia. These included 39 with Streptococcus
      pneumoniae, 4 with Haemophilus influenzae, 2 with Neisseria meningitidis, 3 with
      Salmonella species, and 2 with Staphylococcus aureus. The incidence of bacteremia
      increased at higher temperatures, being 1.9% at temperatures less than or equal
      to 40 degrees C and 5.0% at temperatures greater than 40 degrees C. Younger
      children were more likely to have bacteremia; 3.7% less than or equal to 12
      months of age, 2.4% 13 to 24 months of age, and 1.9% 25 to 36 months of age had
      blood culture results that were positive (not significant). Reevaluation of the
      50 bacteremic patients showed that 9 patients had continued fever, 3 patients had
      persistent bacteremia, pneumonia developed in 1 patient, and meningitis developed
      in 1 patient. It was concluded that (1) 3% of young febrile children with otitis
      media have bacteremia at the time of evaluation, a rate comparable to that
      previously reported in children with no focus of infection; (2) the incidence of
      bacteremia increases at higher temperatures; and (3) most febrile children with
      otitis media do well. The clinician must therefore weigh the potential benefit of
      drawing a blood culture to identify children at risk for complications against
      the inherent cost, inconvenience, and discomfort.

PMID- 1984619
TI  - Controlled trial of a home and ambulatory program for asthmatic children.
AB  - Care of asthmatic children is often episodic and more therapeutic than
      preventive. A 2-year randomized, controlled trial involving 95 children measured
      the impact of a comprehensive home and ambulatory program for pediatric asthma
      management using objective outcome measures. Interventions for the study group
      during the first year included 3-month clinic visits, education, and home visits
      by a specially trained research nurse. Control subjects continued to receive
      regular care from a family physician or pediatrician. Eight-nine subjects (93%)
      completed the study. Study subjects had less school absenteeism than control
      subjects (10.7 vs. 16.0 days, P = .04) and showed significantly better small
      airway function after 1 year. Asthma severity improved in 13 study subjects and
      worsened in 5. The reverse was true for control subjects. Study subjects
      exhibited better metered aerosol technique than control subjects (P = .0005).
      Fewer days were spent in hospital by the study subjects admitted compared with
      control subjects (3.67 vs 11.2 days, P = .02). After 1 year, more study than
      control families (72.1% vs 33.1%, P = .006) reported that their asthmatic child
      took responsibility for the asthma management. The intervention failed to reduce
      exposure to secondhand smoke or to household pets. There were no significant
      differences in medical visits, theophylline levels, or records of asthma
      symptoms. One year after discontinuing the intervention, a marked "washout"
      effect was observed. Comprehensive ambulatory programs of childhood asthma
      management can improve objective measures of illness severity but must be
      sustained.

PMID- 1984620
TI  - Risk of respiratory illness associated with day-care attendance: a nationwide
      study.
AB  - The risk of respiratory and other illnesses in children (age groups: 6 weeks
      through 17 months, 18 through 35 months, and 36 through 59 months) in various
      types of day-care facilities was studied. Children considered exposed to day care
      were those who were enrolled in day care with at least one unrelated child for at
      least 10 hours per week in each of the 4 weeks before the interview; unexposed
      children were not enrolled in any regular child care with unrelated children and
      did not have siblings younger than 5 years of age receiving regular care with
      unrelated children. Although an increased risk of respiratory illness was
      associated with attending day care for children in all three age groups, this
      risk was statistically significant only for children 6 weeks through 17 months of
      age (odds ratio = 1.6; 95% confidence interval = 1.1 to 2.4) and children 18
      through 35 months of age who had no older siblings (odds ratio = 3.4; 95%
      confidence interval = 2.0 to 6.0). In contrast, day-care attendance was not
      associated with an increased risk of respiratory illness in children 18 through
      35 months of age with older siblings (odds ratio = 1.0). For children aged 6
      weeks through 17 months, the exposure to older siblings was associated with an
      increased risk of respiratory illness; however, for children aged 36 through 59
      months, older siblings were protective against respiratory illness. In addition,
      for the children in each age group currently in day care, increased duration of
      past exposure to day care was associated with a decreased risk of respiratory
      illness.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1984621
TI  - 28-day survival rates of 6676 neonates with birth weights of 1250 grams or less.
AB  - Survival rates specific for birth weight, gestational age, sex, and race are
      described for 6676 inborn neonates who weighed less than 1251 g at birth and were
      born during 1986 through 1987. Overall 28-day survival increased with gestational
      age and birth weight, from 36.5% at 24 weeks' gestation to 89.9% at 29 weeks'
      gestation, or from 30.0% for neonates of 500 through 599 g birth weight to 91.3%
      for neonates of 1200 through 1250 g. The expected birth weight-specific survival
      advantage for female neonates and black neonates diminished when the data were
      controlled for gestational age, showing that certain previously reported survival
      advantages are based on lower birth weight for a given gestational age.
      Multivariate analysis showed that all tested variables were significant
      predictors for survival, in order of descending significance: gestational age and
      birth weight, sex, race, single birth, and small-for-gestational-age status. The
      powerful effect of gestational age on survival highlights the need for an
      accurate neonatal tool to assess the gestational age of very low birth weight
      neonates after birth.

PMID- 1984622
TI  - Unsupervised children in vehicles: a risk for pediatric trauma.
AB  - In this study, a series of instances of children injured by a motor vehicle set
      in motion by an unsupervised child are reviewed. During a 24-month period, nine
      such children were identified through a multihospital and coroner's office
      monitoring system in a single urban county. Injuries ranged from multiple
      abrasions and contusions to serious leg and head injuries. Three children died.
      The typical circumstance involved a child releasing the brake or placing the
      vehicle in gear in a private driveway which resulted in the vehicle striking or
      rolling over the victim. In four of the nine cases, the child who set the vehicle
      in motion fell or jumped from the vehicle and then became the injured victim. The
      extent of these unusual motor vehicle-related injuries is unknown because they
      are unlikely to be reported in official police statistics. According to the study
      findings, there is a need to educate the public and health professionals about
      the risks associated with leaving a child unattended in a motor vehicle and the
      hazardous environment of the private driveway. Preventive measures would include
      not leaving a child unattended in a vehicle, locking unattended vehicles to
      prevent access, and redesigning of private driveways.

PMID- 1984624
TI  - Daddy, MD.

PMID- 1984623
TI  - Pediatric emergency room visits: a risk factor for acquiring measles.
AB  - In recent years, measles outbreaks have occurred among unimmunized children in
      inner cities in the United States. From May 1988 through June 1989, 1214 measles
      cases were reported in Los Angeles, and from October 1988 through June 1989, 1730
      cases were reported in Houston. More than half of cases were in children younger
      than 5 years of age, most of whom were unvaccinated. Of cases of measles in
      preschool-aged children, nearly one fourth in Los Angeles and more than one third
      in Houston were reported by one inner-city emergency room. To evaluate whether
      emergency room visits were a risk factor for acquiring measles, in Los Angeles,
      35 measles patients and 109 control patients with illnesses other than measles,
      and in Houston, 49 measles patients and 128 control patients, who visited these
      emergency rooms, were enrolled in case-control studies. Control patients were
      matched to case patients for ethnicity, age, and week of visit. Records were
      reviewed to determine whether case patients had visited the emergency room during
      the period of potential measles exposure, which was defined as 10 to 18 days
      before rash onset, and whether control patients had visited 10 to 18 days before
      their enrollment visit. In Los Angeles, 23% of case patients and 5% of control
      patients (odds ratio = 5.2, 95% confidence interval = 1.7, 15.9; P less than
      .01), and in Houston, 41% of case patients and 6% of control patients (odds ratio
      = 8.4, 95% confidence interval = 3.3, 21.2; P less than .01), visited the
      emergency room during these periods.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1984625
TI  - Constitutional delay of growth: expected versus final adult height.
AB  - Constitutional delay of growth and puberty is believed to represent a variation
      of normal growth, and it is expected that children with this condition will grow
      for a longer duration than average and reach a height that is normal for their
      genetic potential. The records of children with constitutional delay of growth
      and puberty who were initially seen in the Pediatric Endocrine Clinic at the
      Oregon Health Sciences University between 1975 and 1983 were retrospectively
      reviewed. Criteria for study included a height more than 2 SD below the mean, a
      significantly delayed bone age, and a normal growth velocity on follow-up. Forty
      two subjects were located and final adult height measurements were obtained. AT
      contact, the 29 male subjects (mean age = 23.9 years) were 169.5 +/- 4.5 cm tall
      (mean +/- SD), and the 13 female subjects (mean age = 20.5 years) were 156 +/-
      3.8 cm tall. Adult height predictions during follow-up, using either the Bayley
      Pinneau or Roche-Wainer-Thissen method, were close to final adult heights. The
      males were 1.2 SD and the females 1.3 SD below the 50th percentile as adults.
      This finding was not fully explained by genetic short stature; the males fell 5.1
      cm and the females 5.3 cm below target heights based on midparental heights. It
      is concluded that this discrepancy is most likely explained by a selection bias
      of the shortest children referred to and observed in a subspecialty clinic,
      although a defect in human growth hormone secretion or function in children at
      the far end of the spectrum of constitutional delay of growth and puberty cannot
      be excluded.

PMID- 1984626
TI  - Ambulatory blood pressure patterns in children and adolescents: influence of
      renin-sodium profiles.
AB  - A renin-sodium nomogram for normotensive children and adolescents was developed
      at our institution. The ambulatory blood pressure patterns of subjects classified
      by the nomogram were then compared. A biracial sample of 159 children and
      adolescents were classified as having a low, intermediate, or high renin-sodium
      profile based on the relationship between their plasma renin activity and 24-hour
      urinary sodium excretion. Casual (106/58 vs 107/61 vs 106/62 mm Hg) and awake
      (116/69 vs 117/69 vs 116/70 mm Hg) blood pressure values were comparable among
      subjects with low, intermediate, and high renin-sodium profiles. Subjects with
      high renin-sodium profiles, however, had a smaller decline in systolic blood
      pressure with sleep than did subjects with low renin-sodium profiles (7 vs 11 mm
      Hg; P less than .04), and higher diastolic blood pressure readings during sleep
      than subjects with intermediate renin-sodium profiles (65 vs 62 mm Hg; P less
      than .05). Subjects with high renin-sodium profiles also had greater variance of
      diastolic blood pressure readings during sleep than either subjects with low
      renin-sodium profiles (P less than .01) or those with intermediate renin-sodium
      profiles (P less than .02). The blunted nocturnal decline and increased nocturnal
      variance of blood pressure among subjects with high renin-sodium profiles may be
      a marker or mechanism for the future development of essential hypertension.

PMID- 1984627
TI  - Transhepatic portal vein catheterization for localization of insulinomas: a ten
      year experience.
AB  - One of the most important factors in the management of insulinomas is the ability
      to localize the tumor accurately either before or during surgery. We
      prospectively carried out transhepatic portal venous sampling (THPVS) for tumor
      localization in 35 of 40 patients with organic hyperinsulinism during a 10-year
      period. In 32 patients who underwent THPVS and in whom a single tumor was
      subsequently identified surgically, the maximal insulin gradient was located in
      the vicinity of the tumor in 100% of cases. Specific regionalization of the tumor
      on the basis of the site of the maximal insulin gradient to one of three regions
      (the tail, the body/neck region, and the head/uncinate region) gave a sensitivity
      of 81% and a specificity of 91%. In contrast, the use of specific cutoff levels
      for the insulin gradient as a guide to the presence of a tumor in one of these
      three regions did not increase the accuracy, leading instead to a significant
      loss of sensitivity with no comparable increase in specificity. There were no
      major complications from the procedure in any patient. The initial use of
      computed tomographic/ultrasound scanning and selective angiography localized only
      46% of tumors, whereas subsequent THPVS led to the accurate preoperative
      localization of 100% of all tumors submitted to surgery. Although the surgeon
      would have identified 81% of the tumors correctly at operation, in 19% (n = 6) he
      would have failed. Four tumors were in the uncinate and two were in the head. It
      seems that in patients with proved or established organic hyperinsulinism, THPVS
      may continue to be of value, if only to regionalize the tumor, especially those
      in the pancreatic head and uncinate process so as to preclude noncurative
      operations on the body and tail of the pancreas.

PMID- 1984628
TI  - Spontaneous aorto-left renal vein fistula: the "abdominal pain, hematuria, silent
      left kidney" syndrome.
AB  - Spontaneous aorto-left renal vein fistula (ALRVF) is a rare occurrence; with this
      case, only 16 have been reported to date. Common features in patients with ALRVF
      include abdominal pain (81%), hematuria (100%), impaired renal function (85%),
      and nonvisualization of the left kidney (100%). Less common but also present in
      the majority of cases are a left sided bruit (73%), pulsatile abdominal mass
      (63%), and proteinuria (50%). Also important, 94% have a retroaortic left renal
      vein, unlike the six cases of traumatic ALRVF that have been reported. This
      magnifies the diagnostic value of contrast abdominal computed tomographic
      scanning, which demonstrates not only the anomalous location of the left renal
      vein but also the abdominal aortic aneurysm and poor enhancement of the left
      kidney. These findings rule out the possibility of the "nutcracker syndrome"
      (left renal vein compression between aorta and superior mesenteric artery).
      Although confirming the presence of a fistula by early caval opacification,
      aortography does not always distinguish ALRVF from the more common aortocaval
      fistula. This can be accomplished by Duplex scanning with deep probes and even
      preferably color coding of velocity signals. With such precise preoperative
      localization, surgical repair is relatively easy and safe.

PMID- 1984629
TI  - Adenomyomatosis of the gallbladder. A premalignant lesion?
AB  - Gallbladder cancer is the most common malignant tumor of the biliary tract, but
      its early diagnosis is uncommon. The use of ultrasonography has increased the
      detection of benign gallbladder tumors, and the premalignant potential of
      gallbladder adenomas is now undisputed. Adenomyomatosis of the gallbladder has
      recently been suggested to have malignant potential, and we report a case of
      adenocarcinoma of the gallbladder occurring in localized adenomyomatosis that was
      successfully treated by radical curative surgery. The more rigorous use of
      ultrasonography and a more aggressive approach to "benign" polypoid lesions of
      the gallbladder may represent the best way of achieving early diagnosis and cure
      in gallbladder cancer.

PMID- 1984630
TI  - The next step.

PMID- 1984631
TI  - General surgery, a true specialty.

PMID- 1984632
TI  - Is hyperoxia detrimental in sepsis?

PMID- 1984633
TI  - Anticoagulation during intra-aortic balloon counter-pulsation.

PMID- 1984634
TI  - Greenfield filter as primary therapy for deep venous thrombosis and/or pulmonary
      embolism in patients with cancer.
AB  - In 1985, as a result of the high complication rate associated with anticoagulants
      in patients who have cancer and deep venous thrombosis (DVT) and/or pulmonary
      embolism (PE), we established a policy of placing Greenfield filters (GFs) as
      primary therapy instead of anticoagulation. Since 1985 we have been asked to
      consult in the treatment of 18 patients with cancer and with DVT and/or PE, and
      we have placed a GF in each of these patients. This represented 34% (18/53) of
      the filters placed during that same period. Over the same 4-year period, 11
      patients with cancer and DVT and/or PE underwent anticoagulation therapy. The
      purpose of this study was to compare the results of anticoagulation versus GF
      insertion in these two groups of patients. A significantly higher number of major
      complications (n = 4) occurred in the anticoagulation group (p less than 0.05,
      Fisher's exact test) than in the GF group (n = 0). The four complications that
      occurred in the anticoagulation group included three bleeding episodes (tumor
      bleeding, gastrointestinal bleeding, and hip hematoma) and one PE, despite
      adequate anticoagulation. Two patients died as a direct result of these
      complications (PE and gastrointestinal bleeding). The three patients with
      bleeding complications each required a transfusion of more than 3 units of blood.
      All four of the patients with complications had metastatic disease (pancreatic
      carcinoma, chronic lymphocytic leukemia, prostate carcinoma, and uterine
      carcinoma). Although this is a small, nonrandomized, nonprospective study, the
      data seem to indicate that GF placement is safer than anticoagulation for DVT or
      PE in patients with cancer and particularly in patients with metastatic disease.
      We conclude that GF insertions may be a better primary treatment than
      anticoagulation.

PMID- 1984635
TI  - Adult human endothelial cell seeding using expanded polytetrafluoroethylene
      vascular grafts: a comparison of four substrates.
AB  - Prosthetic small-caliber vascular grafts give poorer patency rates than
      autogenous vein grafts, possibly because the former never spontaneously form
      endothelium. Animal studies have shown that endothelialization of prosthetic
      grafts can be encouraged by seeding endothelial cells into the graft at the time
      of surgery, resulting in improved patency. Information regarding the attachment
      characteristics of adult human endothelial cells to prosthetic grafts is,
      however, sparce. Laboratory experiments were performed by use of cell culture
      techniques to compare the attachment characteristics of adult human endothelial
      cells to expanded polytetrafluoroethylene graft material, both untreated and
      treated, with one of four protein substrates--preclotted blood, fibronectin,
      laminin, and type 4 collagen. Attachment characteristics were compared
      quantitatively by use of attachment assays and qualitatively by scanning electron
      microscopy. Attachment to untreated expanded polytetrafluoroethylene was poor but
      could be greatly improved by preclotting or precoating with any of the proteins,
      particularly fibronectin. In preclotted grafts seeded endothelial cells formed a
      virtually confluent monolayer after 1 hour. Cell attachment to the other grafts
      coated with protein was patchy and inconsistent. It is concluded that a rapid
      confluent endothelial lining within a prosthetic vascular graft is possible, and
      of the substrates examined, preclotted blood best encourages cell attachment to
      expanded polytetrafluoroethylene.

PMID- 1984636
TI  - Leucine kinetics in patients with benign disease, non-weight-losing cancer, and
      cancer cachexia: studies at the whole-body and tissue level and the response to
      nutritional support.
AB  - We have performed intraoperative isotopic infusions of carbon 14-labeled leucine
      in 65 patients to define the abnormalities in protein metabolism at both the
      whole-body and tissue level in patients with weight-losing and non-weight-losing
      cancer. Eighteen patients had benign disease, 26 had non-weight-losing cancer,
      and 21 had cancer cachexia. Samples of plasma and expired breath were taken to
      determine rates of whole-body protein synthesis (WBPS), whole-body protein
      catabolism (WBPC), net protein catabolism, and albumin fractional synthetic
      rates. Tissue samples were taken to determine the fractional synthetic rates
      (FSR) of protein in muscle, liver, cancer, and the tissue in which the cancer
      arose. In addition, in 14 patients the effect of nutritional support on protein
      metabolism was assessed. In all parameters examined we were unable to detect any
      significant differences between patients with no cancer and the patients with non
      weight-losing cancer. In contrast, patients with cancer cachexia had a
      significant elevation (p less than 0.005) in WBPC compared with the other two
      groups. WBPS was also elevated (to a lesser extent) in the patients with cancer
      cachexia, and the rate of net protein catabolism was increased significantly (p
      less than 0.05). Patients with cancer cachexia also had significantly higher
      values of FSR of protein in muscle (p less than 0.05), liver (p less than 0.05),
      and albumin (p less than 0.01) compared with the other two groups. In addition,
      the protein FSR in the cancer rose progressively when the values for the primary
      cancer were compared with those for nodal and systemic metastases. Further,
      although nutritional support resulted in an increase in host muscle protein
      synthesis (p less than 0.04), there was no promotion of FSR of protein in cancer.
      We conclude that patients with cancer cachexia are actively losing protein as a
      result of an increase in WBPC that is only partially compensated for by an
      increase in WBPS. There are compensatory increases in protein synthesis in muscle
      and liver, but these increases in host protein synthesis are insufficient to keep
      pace with the combined effect of the accelerated rate of protein synthesis in the
      cancer per se and the accelerated rate of net protein catabolism at the whole
      body level. In response to nutritional support, there is a significant increase
      in the muscle protein synthesis, but we could not demonstrate any increase in
      cancer protein synthesis.

PMID- 1984637
TI  - Pseudomonas aeruginosa bacteremia in patients undergoing liver transplantation:
      an emerging problem.
AB  - In our institution, Pseudomonas aeruginosa bacteremia appeared to occur with
      increasing frequency in patients undergoing liver transplantation. We thus
      conducted a prospective study to define risk factors and outcome in these
      patients. Over a 19-month period 6% of liver transplants were followed by
      Pseudomonas bacteremia. The mean age was 46 years (range, 24 to 67 years). The
      interval between transplantation and onset of bacteremia was 3 to 372 days (mean,
      80). The incidence of Pseudomonas bacteremia in liver transplants was three times
      that of other transplants (heart, lung, kidney). Ninety one percent of infections
      were nosocomial. Polymicrobial bacteremia occurred in 30% of episodes. The portal
      of entry was respiratory in 30%, abdominal in 35%, and biliary in 13%. Four
      patients had recurrent Pseudomonas bacteremia: liver abscess (1), biliary
      obstruction (2), subhepatic abscess (1). Survival at 14 days was 70%. Survival
      rates were significantly lower for patients with hypotension, on mechanical
      ventilators, and increasing severity of illness (p less than 0.05). Survival was
      higher when bacteremia occurred within the first 30 days after transplantation
      compared to after 30 days. A large number (43.4%) of Pseudomonas bacteremias
      occurred after transplant surgery of biliary tract manipulation, while the
      patient was receiving a prophylactic regimen of cefotaxime and ampicillin. P.
      aeruginosa is an important pathogen in the liver transplant recipient; prevention
      may be possible for a subgroup of patients with the use of prophylactic
      antibiotics with activity against P. aeruginosa.

PMID- 1984638
TI  - The effects of dimethyl sulfoxide on aortic prostacyclin production and serum
      thromboxane and plasma fibrinogen levels in rabbits fed a normal versus a
      cholesterol-enriched diet.
AB  - Through an unknown mechanism, dimethyl sulfoxide (DMSO) retards atherogenesis in
      cholesterol-fed rabbits (CFR). We studied the effects on the development of
      lesions and prostacyclin (PGI2) production in the thoracic aorta and total serum
      lipid and cholesterol content of the abdominal aortic serum thromboxane (TXB2)
      and plasma fibrinogen levels in rabbits fed control versus atherogenic diets,
      with and without DMSO. Without DMSO, PGI2 production was significantly higher in
      CFR versus control animals (8.65 +/- 1.0 vs 6.38 +/- 0.3 ng/15 min [p less than
      0.02]). DMSO did not influence PGI2 production in any of the groups but
      significantly reduced the number of atheromatous lesions in CFR (78% +/- 9% vs 8%
      +/- 4% [p less than 0.001]). With DMSO, CFR had a significant reduction in total
      lipid levels (422 +/- 5 vs 300 +/- 21 mg/gm dry wt [p less than 0.01]) and
      cholesterol levels (74 +/- 12.8 vs 31.8 +/- 6.4 mg/gm dry wt [p less than 0.01])
      compared with control animals. Fibrinogen levels were significantly lower in CFR
      versus control animals (0.83 +/- 0.07 vs 2.42 +/- 0.13 mg/ml [p less than 0.01]).
      TXB2 was lower in DMSO plus control versus control animals alone. In conclusion,
      DMSO does not appear to act through changes in PGI2 or fibrinogen activity. Its
      effect in lowering TXB2 in CFR suggests an action on platelet function.

PMID- 1984639
TI  - Beneficial actions of exogenous hyaluronic acid on wound healing.
AB  - To determine the effect of exogenous hyaluronic acid (HA) on healing of
      experimental wounds, responses in the hamster cheek pouch were measured after a
      hole was cut through the tissue with a biopsy punch. Fluorescence-labeled dextran
      was administered intravenously as a macromolecular tracer and the
      microcirculation was observed in vivo with a fluorescence microscope connected to
      a high-resolution television system. In one group a gelatin sponge soaked in 1.5
      ml 16 mg/dl HA in water was applied topically at the time of injury and on
      postinjury days 1, 3, 5, and 7. The control group received the sponge soaked in
      the aqueous vehicle. Every 2 days after injury, the microcirculation was observed
      or histologic specimens were harvested. Wound size decreased almost twice as fast
      with HA compared with its vehicle (p less than 0.05). Healing was defined as time
      for total wound closure with at least one microvessel bridging the site of injury
      and required 16 or more days with vehicle but averaged less than 9 days with HA.
      Early during healing the repair site was surrounded by widespread extravasation
      of the fluorescent tracer, an index of inflammation; this area was reduced by two
      thirds 2 to 4 days after injury with HA compared with its vehicle (p less than
      0.05). The density of perfused microvessels was twofold higher with HA 2 to 4
      days after injury (p less than 0.05). However, microvessel density was similar in
      both groups by 6 days after injury and remained similar for at least 45 days
      after injury, which suggests that HA evoked no unusual angiogenic response.
      Histologic examination of fixed, stained specimens showed increases in
      intravascular leukocytes after injury and treatment-related differences in the
      distribution of intravascular leukocytes in 20 to 40 microns and 40 to 80 microns
      diameter microvessels 1 to 2 days after injury. Otherwise, leukocyte infiltration
      during healing was similar in both groups. The mechanism for the beneficial
      action of HA on healing is unknown. However, several in vitro studies suggest
      that HA is part of a feedback loop that promotes cell proliferation and migration
      in actively growing tissues. Alternatively, the role of HA in water homeostasis
      could favor tissue hydration, which has a well-known beneficial effect on
      healing.

PMID- 1984640
TI  - Nonoperative observation of clinically occult arterial injuries: a prospective
      evaluation.
AB  - Forty-seven patients with 50 clinically occult injuries of major arteries were
      studied prospectively to determine the natural history of these lesions and the
      safety of nonoperative management. Penetrating trauma was the predominant
      mechanism and lower extremity arteries were most commonly involved. The
      morphology of these arterial injuries included 22 cases of intimal flaps, 21
      cases of segmental arterial narrowing, 6 pseudoaneurysms, and 1 acute
      arteriovenous fistula. There was one death as a result of unrelated causes and
      another three injuries operated on immediately after arteriographic diagnosis.
      The remaining 46 injuries were followed up nonoperatively by serial arteriography
      (39) or clinical examination (7) during a mean interval of 3.1 months (range, 3
      days to 27 months). Complete resolution was documented for 29 injuries (63%),
      whereas 3 improved, 9 remained unchanged, and 5 worsened during the period of
      follow-up. All worsened cases involved small or occult pseudoaneurysms that
      subsequently enlarged and then underwent immediate surgical repair without
      subsequent morbidity. Because 89% of the followed injuries never required
      surgery, nonoperative observation appears to be a safe and effective management
      option for clinically occult arterial injuries.

PMID- 1984641
TI  - Gastric duplication cyst communicating with the pancreatic duct: a rare cause of
      recurrent abdominal pain.
AB  - A 41-year-old woman with recurrent attacks of postprandial abdominal pain was
      found on endoscopic retrograde cholangiopancreatography and subsequent computed
      tomographic scan to have an enteric duplication within the substance of the
      pancreas with communication to the pancreatic duct. Celiotomy demonstrated a
      noncontiguous gastric duplication cyst. Internal drainage was curative.

PMID- 1984642
TI  - The N2 neuraminidase of human influenza virus has acquired a substrate
      specificity complementary to the hemagglutinin receptor specificity.
AB  - A survey of 10 human influenza A viruses of the N2 serotype, isolated between
      1957 and 1987, has revealed a drift in neuraminidase linkage specificity. While
      the earliest N2 strains examined exhibit strict specificity for cleavage of the
      NeuAc alpha 2,3Gal sequence, N2 isolates from 1967 to 1968 also show limited
      activity towards the NeuAc alpha 2,6Gal linkage. In strains isolated in 1972 and
      later, the N2 neuraminidase has approximately equal activity towards both types
      of linkages. The NeuAc alpha 2,6Gal linkage cleaved by the later N2
      neuraminidases is the preferred receptor determinant of human H2 and H3
      hemagglutinins. Thus, the acquired neuraminidase specificity of the later
      isolates allows elution of bound virus from erythrocytes derivatized to contain
      the NeuAc alpha 2,6Gal linkage, while earlier isolates, which cleave only the
      NeuAc alpha 2,3Gal sequence, fail to elute from these erythrocytes. These results
      suggest that the observed drift in N2 neuraminidase specificity in the direction
      of the preferred H2 and H3 receptor determinant may facilitate release of progeny
      virus from host cells.

PMID- 1984643
TI  - Association of HSP70 with the adenovirus type 5 fiber protein in infected HEp-2
      cells.
AB  - Although maximal synthesis of HSP70 is induced early (6-12 hr) after adenovirus
      type 5 (Ad5) infection of HEp-2 or HeLa cells, the total amount of HSP70 appears
      to be increased at late times of infection (18-24 hr). Since virion structural
      proteins also accumulate at these times, we investigated the possible interaction
      between Ad5 structural proteins and HSP70 by immunoprecipitation of infected cell
      extracts with antibodies to either ATP-affinity-purified HSP70 or to CsCl
      gradient-purified Ad5 virions. We found that HSP70 and a 62-kDa Ad-specific
      protein coimmunoprecipitated from infected cell extracts. Antibody which
      recognizes one of these two proteins does not cross-react with the other. Thus,
      the association between HSP70 and the 62-kDa protein appears specific. Using
      different antisera to specific adenovirus structural proteins, we have identified
      the 62-kDa protein as the Ad5 fiber protein.

PMID- 1984644
TI  - X-ray powder pattern analysis of cytoplasmic polyhedrosis virus inclusion bodies.
AB  - Cytoplasmic polyhedrosis virus is an insect reovirus which is occluded in
      crystalline inclusion bodies that form in the mid-gut of certain insects.
      Inclusion bodies of cytoplasmic polyhedrosis virus from Bombyx mori were isolated
      and purified. These crystalline bodies, about 1-3 microns in linear size, were
      compacted in a capillary tube while immersed in buffer. X-ray diffraction
      photographs showed powder rings, extending to 8.2 A resolution, which could be
      indexed with a cell measuring a = b = 49.9 +/- 0.4 A, c = 41.5 +/- 0.4 A, alpha =
      beta = gamma = 90 degrees. The polyhedrin protein, which is the major component
      of the inclusion body, has a molecular weight of about 30,000 daltons and, hence,
      there are probably two molecules in the unit cell. Thus, the unit cell is
      monoclinic or possibly triclinic. A Patterson derived from the measured powder
      pattern intensities, assuming monoclinic symmetry, could be interpreted in terms
      of a molecule with two larger globes. Such a structure is roughly consistent with
      the breakdown of the polyhedrin into two larger fragments of molecular weight
      17,000 and 14,000 when raising the pH to near 10. Under these conditions the
      inclusion bodies disintegrate, releasing virus and catalyzing the proteolysis of
      the polyhedrin.

PMID- 1984645
TI  - Retarded processing of influenza virus hemagglutinin in insect cells.
AB  - When expressed in Spodoptera frugiperda cells by a baculovirus vector, the
      hemagglutinin of fowl plague virus has been found to contain palmitic acid in
      covalent hydroxylamine-sensitive linkage, indicating that these cells have the
      capacity to acylate foreign proteins at cysteine residues. Centrifugation on
      sucrose density gradients and immune precipitation with conformation-specific
      antibodies were used to compare trimerization of the hemagglutinin in insect
      cells and in fowl plague virus-infected MDCK cells. Trimerization of the
      hemagglutinin was incomplete in insect cells, and the kinetics of this reaction
      were about three times slower than in vertebrate cells. Similarly, post
      translational proteolytic cleavage occurred in insect cells with a half-time of
      90 min, and a substantial fraction of the hemagglutinin persisted in uncleaved
      form. In contrast, hemagglutinin was almost completely cleaved in MDCK cells, and
      the half-time of cleavage was only 30 min. The data indicate that in insect cells
      trimerization and, as a result, the subsequent processing steps of the
      hemagglutinin, are retarded and less efficient. The possible roles of aberrant
      glycosylation, acidic milieu, and lack of other influenza virus proteins in
      hemagglutinin trimerization are discussed.

PMID- 1984646
TI  - Interference in trans with brome mosaic virus replication by RNA-2 bearing
      aminoacylation-deficient mutants.
AB  - The tRNA-like domain present at the 3' end of each of the three genomic RNAs of
      brome mosaic virus (BMV) encompasses the (-)-strand promoter essential for
      replication. The replicative competence of two BMV RNA-2 transcripts bearing
      mutations delta 5' and 5'AGA in the tRNA-like domain (previously shown by in
      vitro assays to be deficient in tyrosylation) was evaluated in barley
      protoplasts. Transfection of protoplasts with low (2 micrograms) amounts of delta
      5'RNA-2, together with transcripts of wild-type RNA-1 and -3, not only
      incapacitated the replication of RNA-2 but also significantly interfered in trans
      with the synthesis and accumulation of the other viral RNAs. In contrast, RNA-2
      mutants bearing either 5'AGA or M4 (a mutation yielding enhanced minus-strand
      replication activity in vitro) were inhibitory to viral replication only when
      present at a relatively high level (12 micrograms). Coinoculation of protoplasts
      with high levels (12 micrograms) of each of the three RNA-2 mutants and
      transcripts corresponding to wild-type RNA-1, -2 and -3 (2 micrograms each)
      revealed that the mutants were capable of competing in trans, resulting in
      greatly reduced accumulation of the viral RNA and suggesting that their
      expression from constitutive promoters in transgenic plants may provide
      protection against viral infection.

PMID- 1984647
TI  - Altered translation of the matrix genes in Niigata and Yamagata neurovirulent
      measles virus strains.
AB  - Niigata and Yamagata strains measles virus were isolated from subacute sclerosing
      panencephalitis patients. These viruses were defective in virion production and
      expression of matrix (M) protein. The Niigata M protein-coding frame was
      interrupted by an in-frame termination codon, whereas the Yamagata M gene lacked
      the normal translational initiation codon. These mutations prevented translation
      of a normal M protein. However, RNA derived from the cloned Niigata and Yamagata
      M genes was translatable in vitro into low levels of aberrant proteins that
      reacted with M-specific antiserum. These proteins were also translated from
      poly(A)+ RNA from cells infected by Niigata and Yamagata virus strains. The
      aberrant M protein of Niigata virus was initiated at a downstream AUG codon
      created by a second mutation. The Yamagata M gene produced two aberrant proteins:
      one initiated mainly in vitro at an ACG codon, and a second species initiated at
      a downstream site both in vitro and in vivo. These results define the abnormal
      translational functions of the Niigata and Yamagata M genes, and further
      implicate the involvement of M protein defects in chronic central nervous system
      infections by measles virus.

PMID- 1984648
TI  - Interferon-induced proteins: identification of Mx proteins in various mammalian
      species.
AB  - Mx protein controls influenza virus pathogenicity in mice in vivo. It is an
      abundant protein synthesized in response to interferon-alpha/beta. Searches for
      homolog proteins in various animal species have been conducted using several
      methods: (1) radioactive labeling of proteins induced by interferon and analysis
      by 2-D gel electrophoresis, (2) immunoprecipitation, (3) protoblot-ELISA analysis
      of cell-protein extracts, and (4) immunostaining of fixed cells. All mammalian
      species tested so far (including human, horse, and pig, which are prone to
      influenza virus infection) responded to interferon-alpha by synthesizing one or
      two Mx proteins differing in relative molecular weight and pl. The expression of
      Mx proteins within one species differed sometimes between primary cultures of
      diploid cells and established cell lines. Mx proteins were detected in all
      species in the cytoplasm and, in some rodents only, also in the nucleus. This
      study indicates that the site of action of the Mx gene family might be
      cytoplasmic. The conservation and ubiquity of this family of proteins reflects a
      more general and essential cellular function than was initially considered.

PMID- 1984649
TI  - Isolated HE-protein from hemagglutinating encephalomyelitis virus and bovine
      coronavirus has receptor-destroying and receptor-binding activity.
AB  - Bovine coronavirus (BCV) and hemagglutinating encephalomyelitis virus (HEV) from
      swine were found to grow to high titers in MDCK I cells, a subline of Madin Darby
      canine kidney cells. Virus grown in these cells was used to isolate and purify
      the HE-protein. This protein has been shown recently to have acetylesterase
      activity and to function as the receptor-destroying enzyme of BCV. Here we show
      that HEV contains this enzyme, too. The glycoproteins were solubilized by
      treatment of virions with octylglucoside. Following centrifugation through a
      sucrose gradient the surface proteins S and HE (hemagglutinin-esterase) were
      obtained in purified form. After removal of the detergent by dialysis, HE formed
      rosettes as shown by electron microscopy. The purified HE protein retained
      acetylesterase activity and was able to function as a receptor-destroying enzyme
      rendering red blood cells resistant against agglutination by both coronaviruses.
      HE protein released from the viral membrane failed to agglutinate red blood
      cells. However, it was found to recognize glycoconjugates containing N-acetyl-9-O
      acetylneuraminic acid as indicated by a binding assay with rat serum proteins
      blotted to nitrocellulose and by its ability to inhibit the hemagglutinating
      activity of BCV, HEV, and influenza C virus. The purified enzyme provides a
      useful tool for analyzing the cellular receptors for coronaviruses.

PMID- 1984650
TI  - Evidence for spontaneous circle formation in the replication of the satellite RNA
      of tobacco ringspot virus.
AB  - Replication of the satellite RNA of tobacco ringspot virus (sTobRV RNA) has been
      postulated to require rolling circle transcription. The expected product of
      rolling circle transcription, multimeric sTobRV RNA, is known to undergo self
      cleavage in vitro to release unit-length sTobRV RNA. A spontaneous, efficient,
      not enzymically-catalyzed in vitro circularization reaction is characteristic of
      unit-length sTobRV RNA of the less abundant, (-) polarity. We mutated sTobRV RNA
      at two sites that are distant from each other in the polyribonucleotide chain. A
      third form of the sTobRV RNA was mutated at both sites. Multimeric forms of the
      one-site mutants of sTobRV(+)RNA and sTobRV(-)RNA showed, respectively,
      undiminished and slightly diminished self-cleavage, whereas the spontaneous
      circularization of each one-site-mutated, unit-length sTobRV(-)RNA was greatly
      reduced, compared to the reactions of wild-type sTobRV RNA and the two-site
      mutant. The two-site mutant and the wild-type sTobRV RNAs replicated with similar
      efficiency. They reduced the titer of, and severity of, symptoms induced by
      coinoculated tobacco ringspot virus (TobRV). When coinoculated with TobRV,
      neither one-site mutant increased or provided protection against TobRV. Rather,
      each induced a substantial accumulation of what is apparently an endogenous form
      of sTobRV RNA. Our results are consistent with the formation of circular sTobRV(
      )RNA as an essential step in sTobRV RNA replication.

PMID- 1984651
TI  - Altered function of the tobacco mosaic virus movement protein in a hypersensitive
      host.
AB  - The N gene in Nicotiana sp. confers hypersensitive resistance to all strains of
      tobacco mosaic virus (TMV) and limits the rate of virus spread in infected
      leaves. To examine the role of the movement protein (MP) of TMV in the
      hypersensitive reaction (HR), transgenic Nicotiana tabacum cv. Xanthi-nc
      (genotype NN) plants that express the MP gene were produced and the molecular
      size exclusion limit of plasmodesmata in leaf mesophyll cells was monitored. At
      the HR-permissive temperature (24 degrees) movement from cell to cell of
      fluorescein isothiocyanate-labeled dextran of molecular mass 3.9 kDa was detected
      while 9.4-kDa molecules failed to move. At the HR-nonpermissive temperature (33
      degrees) the 9.4-kDa probe moved readily from cell to cell. In contrast, in
      transgenic Xanthi (genotype nn) which express the MP gene the 9.4-kDa probe moved
      from cell to cell at 24 and 33 degrees. These results suggest that the N gene may
      modify the ability of the MP to alter plasmodesmata molecular exclusion limits,
      although expression of the TMV-MP gene alone did not induce the HR. Furthermore,
      when MP(+) Xanthi-nc tobacco lines were inoculated with a TMV that lacked a MP
      gene the HR was induced, and the concentration of MP in the transgenic lines was
      correlated with the degree of the HR.

PMID- 1984652
TI  - Sequence and crystallization of influenza virus B/Beijing/1/87 neuraminidase.
AB  - Influenza B/Beijing/1/87 neuraminidase heads were isolated from virus via trypsin
      digestion and characterized by PAGE, N-terminal sequencing, electron microscopy,
      and enzyme activity. The heads were crystallized into two crystal forms;
      tetragonal plates, like other neuraminidase crystals described before, that
      diffract to medium resolution (3 A) and a new form consisting of trigonal prisms
      or needles that diffract to high resolution (at least 2 A). The gene segment
      coding for neuraminidase was sequenced and compared with the neuraminidase
      sequence of B/Lee/40. The deduced amino acid sequences for neuraminidase showed
      only a 7% difference, whereas those for the NB proteins differed by 20%.

PMID- 1984653
TI  - Linker mutation scanning of the genes encoding the adenovirus type 5 terminal
      protein precursor and DNA polymerase.
AB  - The replication of adenovirus DNA requires, in addition to several host factors,
      three virus-encoded proteins: a DNA binding protein, the precursor of the
      terminal protein (pTP), and a DNA polymerase (Ad pol). Ad pol and pTP form a
      tight complex that is necessary for the initiation step in DNA replication. To
      perform mutation scanning of the adenovirus type 5 pTP and Ad pol a series of in
      frame linker insertions of a 12-mer oligonucleotide d(CCCATCGATGGG) were
      introduced into cloned viral DNA fragments containing coding sequences of these
      proteins. The insertions are located at recognition sites for several blunt end
      cutting restriction endonucleases. Forty different sites were mutagenized and the
      mutated genes were transferred to a plasmid that contains the left 42% of the
      adenovirus genome. They were rebuilt into the viral genome by means of in vivo
      recombination between plasmid DNA and digested adenovirus DNA-TP complex. The
      resulting viral genomes were tested for viability and rescued virus was analyzed
      for the presence of the inserted linker oligonucleotide. This procedure resulted
      in recovery of a number of viable virus mutants with insertions in the pTP or Ad
      pol genes, all of which are phenotypically silent. The other mutations did not
      allow virus production. The positions of these apparent lethal codon insertion
      mutations were useful to identify regions of functional importance in both
      proteins. It can be concluded that the precursor-specific region of pTP plays an
      important role in virus multiplication.

PMID- 1984655
TI  - The molecular biology of swinepox virus. I. A characterization of the viral DNA.
AB  - Swinepox virus (SPV), the prototype member of the Suipoxvirus genus, is
      uncharacterized at the molecular level. We have analyzed the DNA of SPV and
      demonstrate that the genome is 175 kb in size and like the more commonly studied
      Orthopoxvirus, Avipoxvirus, and Leporipoxvirus genera, is terminally cross-linked
      and contains inverted terminal repetitions (ITRs). In addition, the ITRs are
      unstable, probably due to the presence of a variable number of direct repeats of
      approximately 70 bp in length. Restriction enzyme cleavage maps for the enzymes
      HindIII, AvaI, HaeII, KpnI, BglI, SalI, and XhoI are also presented.

PMID- 1984654
TI  - Transfer of the movement protein gene between two tobamoviruses: influence on
      local lesion development.
AB  - The effects of transfer of the movement gene between the tobamoviruses tobacco
      mosaic virus (TMV) and tobacco mild green mosaic virus (TMGMV) were studied. The
      movement protein (MP) gene of TMGMV was cloned into an infectious cDNA of TMV to
      build the recombinant virus V23. V23, like TMV and TMGMV, caused systemic
      infection in Nicotiana tabacum Xanthi. In N. sylvestris V23 and TMV spread
      systemically although TMGMV produces necrotic local lesions on this host. V23 and
      TMV cause systemic infection on tomato plants while TMGMV does not infect tomato.
      In Xanthi nc plants, V23 produced necrotic local lesions similar in size to those
      produced by TMGMV. On the other hand in transgenic Xanthi nc tobacco plants that
      express a gene encoding the MP of TMV the necrotic lesions produced by V23 and
      TMGMV were similar in size to those produced by TMV. These results indicate that
      the size of necrotic lesions produced by TMGMV and TMV on Xanthi nc plants is
      influenced by the MP gene.

PMID- 1984656
TI  - High susceptibility of FVB/N mice to the paralytic disease induced by ts1, a
      mutant of Moloney murine leukemia virus TB.
AB  - The ts1 mutant of Moloney murine leukemia virus TB causes a degenerative
      neurologic and immunologic disease in susceptible strains of mice. This disease
      syndrome is characterized by development of spongiform encephalomyelopathy
      resulting in hindlimb paralysis, generalized bodywasting, and marked thymic
      atrophy associated with immune deficiency. The viral genetic determinants
      responsible for hindlimb paralysis in BALB/c and CFW/D mice have been localized
      to two point mutations in the env gene: one results in a Val-25----IIe
      substitution in the envelope precursor polyprotein gPr80env and the other, in an
      Arg-430----Lys substitution in the gp70. In this report we present studies
      showing that FVB/N mice were highly susceptible to ts1 and exhibited the shortest
      and most uniform latency period of all the murine strains tested. In addition, we
      have found that, unlike in CFW/D and BALB/c mice, only the Val-25----IIe
      substitution in the gPr80env is required to induce hindlimb paralysis in FVB/N
      mice. Our studies show that there was enhanced replication of ts1 in all tissues
      of FVB/N mice and that the virus titer in the spinal cord was more than 10-fold
      higher in FVB/N than in BALB/c mice by 30 days postinoculation, when the clinical
      signs of paralysis became evident in FVB/N mice. Apparently, other host factors
      that do not require the Arg-430----Lys substitution allowed high levels of viral
      replication within the central nervous system of FVB/N mice. These results,
      together with the finding that 100% of FVB/N mice that were inoculated with ts1
      at 5 days of age developed hindlimb paralysis at 30-60 days postinoculation,
      whereas only 33% of 5-day-old BALB/c mice developed hindlimb paralysis with a
      much longer latency period, suggest that subtle virus-host interactions determine
      the incidence, the latency period, and the severity of the disease caused by ts1.

PMID- 1984657
TI  - Infectious in vitro transcripts from a cloned cDNA of barley yellow dwarf virus.
AB  - A full-length cDNA clone of barley yellow dwarf virus (BYDV-PAV serotype) has
      been constructed and fused to the bacteriophage T7 RNA polymerase promoter. RNA
      transcripts produced in vitro, either capped or uncapped, were infectious in
      Triticum monococcum protoplasts. Protoplasts inoculated with in vitro-transcribed
      BYDV RNA accumulated coat protein, synthesized new viral RNAs, and produced virus
      particles. Aphid feeding on extracts from protoplasts inoculated with in vitro
      RNA transcripts can be used to transfer the virus progeny to whole plants.
      Introduction of mutations which interrupt specific BYDV-PAV open reading frames
      (ORFs) V and VI eliminated infectivity while an ORF I-mutant remained infectious.
      Infectious RNA transcripts derived from BYDV cDNA clones will facilitate analysis
      of the molecular aspects of BYDV infection and further enhance our understanding
      of this economically important virus.

PMID- 1984658
TI  - The S2 subunit of the spike glycoprotein of bovine coronavirus mediates membrane
      fusion in insect cells.
AB  - The hemagglutinin/esterase (HE), spike precursor (S) and the S1 and S2 subunits
      of the spike precursor protein of bovine coronavirus were expressed in Spodoptera
      frugiperda (Sf9) cells, and the cell-fusing activity of each recombinant
      glycoprotein was examined. Extensive syncytia formation was observed in cells
      infected with the S2 recombinant but not with the HE or S1 recombinant
      baculoviruses. Fusion of Sf9 cells expressing the intact S protein precursor was
      evident after trypsin treatment. These results demonstrate that proteolytic
      cleavage of the S spike precursor is required for fusion induction and that the
      fusion is mediated by the S2 subunit. These observations may reflect the
      biological role of the S2 subunit in fusion-penetration during bovine coronavirus
      infection.

PMID- 1984659
TI  - Efficient in vitro translation and processing of the rubella virus structural
      proteins in the presence of microsomes.
AB  - In the structural protein open reading frame (SP-ORF) of rubella virus (RUB), the
      sequences for the three virion proteins occur in the order NH2-C-E2-E1-COOH with
      hydrophobic, consensus signal sequences preceding the amino termini for each of
      the two membrane proteins (T. K. Frey and L. D. Marr, 1988 Gene 62, 85-100). In
      vitro translation in the presence of microsomes of RNA transcripts from a plasmid
      containing the SP-ORF resulted in production and accurate processing of the three
      structural proteins. Since in the absence of microsomes the 110-kDa precursor of
      these proteins is produced, this finding indicated that the cleavage events in
      processing of the precursor were mediated by signalase. To study the C-E2
      processing event, a DNA construct was made which contained the sequences for E2
      beginning at the NH2 terminus of the hydrophobic consensus signal and extending
      through to the NH2 terminus of E1. In vitro translation of transcripts from this
      construct in the presence of microsomes resulted in accurate processing of E2
      confirming that the hydrophobic sequence was a signal sequence and demonstrating
      it could function externally as well as internally within the 110-kDa precursor.
      To determine if the E2 signal was maintained on C after cleavage of the precursor
      by signalase, the SP-ORF plasmid was mutagenized to place translation termination
      codons at either the NH2 or COOH side of the E2 signal sequence such that C
      protein lacking or containing the E2 signal would be produced. As expected, the C
      minus-signal protein migrated more rapidly in polyacrylamide gels than did the C
      plus-signal protein. C translated from the SP-ORF construct as well as authentic
      C from infected cells comigrated with the C-plus-signal protein, indicating that
      the E2 signal was not removed. In a corollary study, it was found that RUB C
      protein was phosphorylated in vivo, although the percentage of the protein
      phosphorylated was not determined.

PMID- 1984660
TI  - Deletion of 55 open reading frames from the termini of vaccinia virus.
AB  - Each copy of the inverted terminal repeat of vaccinia virus consists of 8 kb of
      DNA containing 9 ORFS flanked near the terminus of the genome by 4 kb of
      repetitive DNA which in turn contains blocks of tandem repeats. Using plasmids
      containing repetitive DNA as the external arm, we have generated deletions at
      both the left and the right termini of the vaccinia genome. We report here the
      engineered deletion within a single vaccinia virus of 32.7 kb of DNA (including
      38 ORFS) from the left terminus and 14.9 kb of DNA (including 17 ORFS) from the
      right terminus.

PMID- 1984661
TI  - Transactivation in a geminivirus: AL2 gene product is needed for coat protein
      expression.
AB  - The beta-glucuronidase (GUS) reporter gene was used to replace the coat protein
      gene (open reading frame AR1) of tomato golden mosaic virus (TGMV) and
      transiently expressed in tobacco protoplasts. While these TGMV/GUS genomes gave a
      high level of GUS activity, genomes which also contained a mutation in the AL2
      open reading frame (TGMV/GUS/AL2-) did not express GUS. GUS activity could be
      restored by cotransfecting protoplasts with the TGMV/GUS/AL2- genome and a wild
      type TGMV genome. Thus, the AL2 gene product transactivates expression of TGMV
      coat protein gene.

PMID- 1984662
TI  - Polymerase-related polypeptides associated with woodchuck hepatitis core antigen
      (WHcAg) particles.
AB  - The woodchuck hepatitis virus (WHV) polymerase (pol)-encoded polypeptide(s),
      obtained from purified virus nucleocapsid particles, have been characterized by
      Western blotting. Peptide antibodies to amino-terminal (residues 32-45, WHV pol
      6) and carboxy-terminal (residues 861-879, WHV pol-1) sequences were used, in
      addition to monoclonal antibodies made from purified woodchuck hepatitis core
      antigen (WHcAg) particles. One of the monoclonal antibodies, WC pol-11,
      specifically bound WHV pol-1. Both peptide and monoclonal anti-WHV pol-1 also
      bound a recombinant DNA-produced WHV polymerase polypeptide. These antibodies
      specifically detected WHcAg-associated polymerase polypeptides at 65,000 (p65)
      and 31,000 (p31) Da by Western blotting. These results support the conclusion
      that WHV pol-11 has anti-pol reactivity and that it binds the carboxyl-terminal
      sequences of the WHV polymerase. The finding that these reagents also
      specifically bind to corresponding sequences from the carboxy terminus of the
      hepatitis B virus polymerase suggests that these viral polymerases are cross
      reactive. Finally, anti-WHV pol-6 did not bind either WHcAg p65 or p31,
      suggesting that both of these polypeptides have different amino-terminal but the
      same carboxy-terminal sequences.

PMID- 1984663
TI  - Structure and expression of the woodchuck herpesvirus genome.
AB  - This report describes the genome structure and location from which immediate
      early transcription originates in the recently characterized woodchuck
      herpesvirus (herpesvirus marmota: HVM). Cross-hybridization of restriction
      fragments indicates that the HVM genome contains a tandem array of 1.5-kb repeat
      units. Additionally, terminal labeling and exonuclease experiments demonstrate
      that the repeated sequences lie at the termini of the genome. Hybridization of
      probes representing immediate-early transcription indicates that only a single
      predominant species of immediate-early RNA originates from a region near one end
      of unique sequences in the HVM genome. These results show remarkable similarity
      with group 2 of the gammaherpesvirinae. However, no homology was detected by
      conventional Southern blot hybridization between HVM and the gamma-2 prototype,
      herpesvirus saimiri. Therefore, we propose HVM to be a new member of the
      gammaherpesvirinae subfamily of herpesviruses.

PMID- 1984664
TI  - The cytoplasmic tail of HIV-1 gp160 contains regions that associate with cellular
      membranes.
AB  - The HIV-1 envelope glycoprotein gp160 associates with cellular membranes via a
      discrete transmembrane domain. Unlike other retroviral envelope proteins,
      however, gp160 also forms a secondary association with the lipid bilayer mediated
      by one or more regions located in the cytoplasmic tail. We have expressed the
      full cytoplasmic tail sequence of gp160, as a fusion protein with the HSV-1
      glycoprotein D signal sequence, transiently in a human embryonic kidney cell
      line. Our results show that in the absence of any defined transmembrane domain or
      stop transfer sequence, the protein corresponding to the cytoplasmic tail of HIV
      1 gp160 formed stable interactions with cellular membranes that mediated its
      export to the cell surface.

PMID- 1984665
TI  - Processing, secretion, and immunoreactivity of carboxy terminally truncated
      dengue-2 virus envelope proteins expressed in insect cells by recombinant
      baculoviruses.
AB  - Two recombinant baculoviruses were constructed by inserting via the transfer
      vector pAcYM1 the genes coding for the structural proteins of dengue (DEN)-2
      virus downstream from the polyhedrin promoter of Autographa californica nuclear
      polyhedrosis virus. The two recombinants differed in truncation of 26 and 71
      amino acids, respectively, in the carboxy-terminal sequence of DEN-specific
      envelope (E) glycoprotein. Recombinant DEN-2 E glycoproteins were processed and
      transported to the surface of Spodoptera frugiperda Sf9 cells infected with both
      viruses. We show that about one-third of the E glycoprotein minus its whole C
      terminal hydrophobic anchor domain was secreted into an endoglycosidase H
      resistant form. The type-specific neutralizing epitopes were conserved in the
      recombinant proteins as shown with a panel of monoclonal antibodies.

PMID- 1984666
TI  - Comparison of the genome organization of toro- and coronaviruses: evidence for
      two nonhomologous RNA recombination events during Berne virus evolution.
AB  - Recently, toroviruses and coronaviruses have been found to be ancestrally related
      by divergence of their polymerase and envelope proteins from common ancestors. In
      addition, their genome organization and expression strategy, which involves the
      synthesis of a 3'-coterminal nested set of mRNAs, are comparable. Nucleotide
      sequence analysis of the genome of the torovirus prototype, Berne virus (BEV),
      has now revealed the results of two independent nonhomologous RNA recombinations
      during torovirus evolution. Berne virus open reading frame (ORF) 4 encodes a
      protein with significant sequence similarity (30-35% identical residues) to a
      part of the hemagglutinin esterase proteins of coronaviruses and influenza virus
      C. The sequence of the C-terminal part of the predicted BEV polymerase ORF1a
      product contains 31-36% identical amino acids when compared with the sequence of
      a nonstructural 30/32K coronavirus protein. The cluster of coronaviruses which
      contains this nonstructural gene expresses it not as a part of their polymerase,
      but by synthesizing an additional subgenomic mRNA.

PMID- 1984667
TI  - Molecular cloning and sequence analysis of bovine respiratory syncytial virus
      mRNA encoding the major nucleocapsid protein.
AB  - The nucleotide sequence of the gene encoding the major nucleocapsid (N) protein
      of bovine respiratory syncytial virus (BRSV) has been determined. The N mRNA is
      1196 nucleotides long with a single, large open reading frame. The derived
      polypeptide has 391 amino acids corresponding to a calculated molecular weight of
      42,600 Da. This is in agreement with the molecular weight of 43,000 Da determined
      for the BRSV N protein by SDS-polyacrylamide gel electrophoresis (PAGE).
      Comparison of the nucleotide sequence of BRSV N gene with the sequence of the N
      gene of human respiratory syncytial virus (HRSV) revealed a homology of 80.7%.
      There is a 93.3% homology at the amino acid level between the N proteins of BRSV
      and HRSV. The 5'- and 3'-terminal untranslated sequences that are conserved among
      HRSV mRNAs were also identified in the N mRNA of BRSV. The results indicate that
      the N genes are highly conserved in the bovine and human strains of respiratory
      syncytial virus.

PMID- 1984668
TI  - Infectivity and complete nucleotide sequence of the cloned genomic components of
      a bipartite squash leaf curl geminivirus with a broad host range phenotype.
AB  - Through cloning and molecular analysis we have identified two highly homologous
      bipartite geminiviruses as causing squash leaf curl disease. Mechanical and
      Agrobacterium-mediated inoculation of plants with cloned viral DNA components
      identified the two genomic components of SqLCV-E, a squash leaf curl virus with
      an unexpectedly broad host range for a whitefly-transmitted geminivirus.
      Nucleotide sequence analysis of the genome of this virus showed it to have the
      same bipartite component organization characteristic of other whitefly
      transmitted geminiviruses. Sequence comparison with the genomic components of
      tomato golden mosaic virus and bean golden mosaic virus revealed a close
      evolutionary relationship with these two bipartite geminiviruses, with which
      SqLCV-E shares common hosts. These studies provide clear molecular evidence for
      the assignment of SqLCV to the subfamily of bipartite geminiviruses.

PMID- 1984669
TI  - Molecular characterization of two bipartite geminiviruses causing squash leaf
      curl disease: role of viral replication and movement functions in determining
      host range.
AB  - The genomes of two distinct, but highly homologous, bipartite geminiviruses have
      been identified in and cloned from extracts of squash leaf curl diseased field
      squash. These two squash leaf curl viruses (SqLCVs) have covalently closed,
      circular single-stranded DNA genomes with the same bipartite component
      organization characteristic of other whitefly-transmitted geminiviruses.
      Infectivity studies using virus preparations or cloned viral genomic components
      on different potential host plants demonstrated that these two SqLCVs have
      different host range phenotypes which can be explained by specific interactions
      among the different viral genomic components that act to influence viral
      replication and systemic movement in the plant. Analysis of Agrobacterium
      inoculated leaf discs demonstrated that replication of the restricted virus was
      rescued in trans by the nonrestricted virus, providing an explanation for the
      mixtures of viral DNA components often found in particular hosts in the field.
      Sequence analysis of the common regions of these two SqLCVs identified a 13-base
      deletion in the restricted virus as compared to the nonrestricted virus,
      suggesting a potential sequence alteration likely to be involved in their host
      range phenotypic differences and strengthening the conclusion based on
      hybridization studies of their close evolutionary relationship. Also identified
      in the original field squash was a defective viral component which appeared to
      interfere with movement of the restricted SqLCV in its normally permissive hosts
      and accounted for another aspect of host range variation observed for this virus.

PMID- 1984670
TI  - The genes associated with trans-dominance of the influenza A cold-adapted live
      virus vaccine.
AB  - Segment 7 (M) of the cold-adapted live influenza A virus vaccine plays a primary
      role in the ability of this virus to interfere with the replication of wild-type
      influenza A viruses. This conclusion is based on several lines of evidence.
      Single gene reassortant viruses derived by crossing influenza A/Ann Arbor/6/60
      (H2N2) cold-adapted donor virus with an epidemic wild-type strain, A/Korea/1/82
      (H3N2), were tested for their ability to interfere with wild-type parental virus
      in the Madin-Darby line of canine kidney cells and embryonated eggs. It was
      apparent in both hosts that the single gene reassortant carrying segment 7 (M)
      derived from the cold-adapted virus was dominant over wild-type virus. Additional
      confirmation of the role of segment 7 (M) in trans-dominance of the cold-adapted
      vaccine virus was derived from the analysis of reassortants produced by mixed
      infection by a wild-type virus and its cold-adapted reassortant vaccine strain.
      After three serial passages, the virus yield contained a high proportion of
      reassortants carrying segment 7 (M) of the cold-adapted parental strain. When
      used in mixed infections, these reassortants were dominant over the replication
      of the parental wild-type virus.

PMID- 1984671
TI  - Immunocytochemical localization of growth hormone and growth hormone-releasing
      hormone immunoreactivity in the brain and pituitary of the little brown bat.
AB  - Anterior pituitary cells exhibiting growth hormone (GH) immunoreactivity and
      forebrain neurons containing growth hormone-releasing hormone (GHRH)
      immunoreactivity were identified in little brown bats (Myotis lucifugus) using
      light microscopic immunocytochemistry. Pituitary somatotropes appeared as ovoid
      or polyhedral cells that were distributed throughout most of the pars distalis,
      with the exception of its most rostral region where this cell type was scarce. GH
      immunoreactive cells occupied approximately one-third of the total volume of the
      pars distalis; this proportion did not differ significantly between males and
      females or in bats collected at different times of year. Neuronal perikarya
      containing immunoreactive GHRH were observed in the hypothalamic arcuate and
      suprachiasmatic nuclei, as well as in the cortical and subcortical telencephalon.
      Fibers were most evident in the median eminence, paraventricular and
      periventricular nuclei, and molecular layer of the cerebral cortex. Fine fibers
      were also accumulated in the bed nucleus of the stria terminalis and in the
      amygdala.

PMID- 1984672
TI  - Ultrastructural and cytoarchitectural features of lymphoreticular organs in the
      colon and rectum of adult BALB/c mice.
AB  - The structure and function of colonic mucosal lymphoid organs remain largely
      unexplored, especially in the rectum hidden within the pelvic vault. Two-month
      old female BALB/c mice were anesthetized, and the entire colon was removed from
      cecum to anus. Distal colonic patches were then prepared for electron microscopy
      or were quick-frozen and sectioned for immunoperoxidase localization of B cells
      and T cell subsets. Aggregated lymphoid follicles were distributed irregularly
      along the entire colon with an average of 1.4 patches per centimeter of colon
      length. There were large collections of follicles opposite the ileocecal valve
      (cecal patches), variable numbers of patches throughout the colon, and at least
      one patch within 10 mm of the anus (rectal patch). Follicles were adjacent to
      branching crypts lined by epithelium infiltrated by lymphoid cells and containing
      few goblet cells. In electron micrographs, M cells were identified by their
      short, irregular microvilli; intraepithelial lymphoid cells; reduced lysosomal
      dense bodies; and an expanded tubulovesicular network. Small germinal centers
      were seen. Cytoarchitectural components of colonic lymphoid follicles and Peyer's
      patch follicles were remarkably similar, despite differences in surrounding
      mucosa and luminal microbial exposure. The presence of organized lymphoid tissue
      with M cells and germinal centers suggests that transepithelial particle
      transport and antigen recognition can take place in the rectum. Whether such
      tissue has the capacity for uptake of luminal microorganisms is of particular
      interest, not only because colonic follicles may be sites for local initiation of
      immune responses but also because they may be important entry points for systemic
      infection.

PMID- 1984673
TI  - Subcellular distribution of [3H]-dexamethasone mesylate binding sites in Leydig
      cells using electron microscope radioautography.
AB  - The present view is that glucocorticoid hormones bind to their cytoplasmic
      receptors before reaching their nuclear target sites, which include specific DNA
      sequences. Although it is believed that cytoplasmic sequestration of steroid
      receptors and other transcription factors (such as NFKB) may regulate the overall
      activity of these factors, there is little information on the exact subcellular
      sites of steroid receptors or even of any other transcription factors. Tritiated
      (3H)-dexamethasone 21-mesylate (DM) is an affinity label that binds covalently to
      the glucocorticoid receptor (GR), thereby allowing morphological localization of
      the receptor at the light and electron microscope levels as well as for
      quantitative radioautographic (RAG) analysis. After injection of 3H-DM into the
      testis, a specific radioautographic signal was observed in Leydig cells, which
      correlated with a high level of immunocytochemically demonstrable GR in these
      cells at the light-microscope level. To localize the 3H-DM binding sites at the
      electron microscope (EM) level, the testes of 5 experimental and 3 control
      adrenalectomized rats were injected directly with 20 microCi 3H-DM; control rats
      received simultaneously a 25-fold excess of unlabeled dexamethasone; 15 min
      later, rats were fixed with glutaraldehyde and the tissue was processed for EM
      RAG analysis combined with quantitative morphometry. The radioautographs showed
      that the cytosol, nucleus, smooth endoplasmic reticulum (sER), and mitochondria
      were labeled. Since the cytosol was always adjacent to tubules of the sER, the
      term sER-rich cytosol was used to represent label over sER networks, which may
      also represent cytosol labeling due to the limited resolution of the
      radioautographic technique. Labeling was highest in sER-rich cytosol and
      mitochondria, at 53% and 31% of the total, respectively. Cytosol (exclusively of
      all organelles) and nucleus showed comparatively weak labeling, at 9% and 7%,
      respectively. This study thus clearly establishes with the electron microscope,
      the localization of glucocorticoid binding sites using DM. It remains to be
      determined whether or not these DM binding sites represent bona fide
      glucocorticoid receptors or nonreceptor proteins that bind DM. Whereas the
      functional significance of the subcellular distribution of DM is not known, the
      labeling of the cytosol may represent localization of the steroid and GR in their
      traditional compartment. The steroid antagonistic properties of DM may have
      prevented the DM-GR complexes from translocating to the nucleus. However, the
      significant labeling of the sER-rich cytosol and mitochondria was unexpected and
      raises intriguing questions that are being addressed in current studies.

PMID- 1984674
TI  - Changes in cells's secretory organelles and extracellular matrix during
      endochondral ossification in the mandibular condyle of the growing rat.
AB  - The mandibular condyle from 20-day-old rats was examined in the electron
      microscope with particular attention to intracellular secretory granules and
      extracellular matrix. Moreover, type II collagen was localized by an
      immunoperoxidase method. The condyle has been divided into five layers: (1) the
      most superficial, articular layer, (2) polymorphic cell layer, (3) flattened cell
      layer, (4) upper hypertrophic, and (5) lower hypertrophic cell layers. In the
      articular layer, the cells seldom divide, but in the polymorphic layer and upper
      part of the flattened cell layer, mitosis gives rise to new cells. In these
      layers, cells produce two types of secretory granules, usually in distinct stacks
      of the Golgi apparatus; type a, cylindrical granules, in which 300-nm-long
      threads are packed in bundles which appear "lucent" after formaldehyde fixation;
      and type b, spherical granules loaded with short, dotted filaments. The matrix is
      composed of thick banded "lucent" fibrils in a loose feltwork of short, dotted
      filaments. The cells arising from mitosis undergo endochondral differentiation,
      which begins in the lower part of the flattened cell layer and is completed in
      the upper hypertrophic cell layer; it is followed by gradual cell degeneration in
      the lower hypertrophic cell layer. The cells produce two main types of secretory
      granules: type b as above; and type c, ovoid granules containing 300-nm-long
      threads associated with short, dotted filaments. A possibly different secretory
      granule, type d, dense and cigar-shaped, is also produced. The matrix is composed
      of thin banded fibrils in a dense feltwork. In the matrix of the superficial
      layers, the "lucency" of the fibrils indicated that they were composed of
      collagen I, whereas the "lucency" of the cylindrical secretory granules suggested
      that they transported collagen I precursors to the matrix. Moreover, the use of
      ruthenium red indicated that the feltwork was composed of proteoglycan; the
      dotted filaments packed in spherical granules were similar to, and presumably the
      source of, the matrix feltwork. The superficial layers did not contain collagen
      II and were collectively referred to as perichondrium. In the deep layers, the
      ovoid secretory granules displayed collagen II antigenicity and were likely to
      transport precursors of this collagen to the matrix, where it appeared in the
      thin banded fibrils. That these granules also carried proteoglycan to the matrix
      was suggested by their content of short dotted filaments. Thus the deep layers
      contained collagen II and proteoglycan as in cartilage; they were collectively
      referred to as the hyaline cartilage region.

PMID- 1984675
TI  - Inflammatory macrophages in the dog contain high amounts of intravesicular
      ferritin and are associated with pouches of connective tissue fibers.
AB  - We have studied the subcellular distribution of ferritin in inflammatory
      macrophages present in regional lymph nodes from dogs subjected to a pulmonary
      inflammatory reaction. The inflammatory reaction was induced by intrabronchial
      instillation of calcium tungstate (CaWO4), a water-insoluble powder. Ferritin was
      identified by electron microscopy, and its electron density was enhanced by the
      use of a modified Perls method. From day 14 on after the CaWO4 deposition,
      tungsten-positive lymph node macrophages showed a massive accumulation of
      ferritin. Most of the ferritin was stored in membrane-bounded vesicles that
      showed heterogeneous concentrations of the protein. A significant complement of
      ferritin was also detected in the cytoplasmic ground substance of phagocytes. The
      cell surface of the ferritin-rich, tungsten-positive macrophages showed deep
      infoldings that encompassed small pockets of connective tissue fibers. These
      features were not observed in control samples or in lymph nodes from dogs
      subjected to CaWO4-induced inflammation for periods shorter than 1 week. Our data
      indicate that inflammatory macrophages greatly increase their content of ferritin
      macrophages greatly increased their content of ferritin and that ferritin is
      stored predominantly by a membrane-bounded vesicular compartment. This is in
      contrast with suggestions that the inflammation-induced increase in macrophage
      iron is restricted to the labile pool of iron and it does not involve the iron
      bound to ferritin molecules. Our observation of nodules of connective-tissue
      fibers in intimate topographical association with ferritin-rich macrophages may
      indicate that the increase in intracellular ferritin in the macrophage is in some
      way related to the secretion of factors by the phagocyte that will stimulate
      fibrillogenesis by neighboring fibroblats.

PMID- 1984676
TI  - Circulating hyaluronan in the myelofibrosis/osteomyelosclerosis syndrome and
      other myeloproliferative disorders.
AB  - The serum concentration of hyaluronan (HYA) was determined in 59 patients with
      various myeloproliferative disorders, including 33 patients with idiopathic
      myelofibrosis. In 18 patients the serum concentration of the aminoterminal
      propeptide of type III procollagen (PIIINP) was measured concomitantly. Raised
      serum HYA levels were seen in patients with active disease compared with age
      matched healthy subjects, whereas no significant difference in serum HYA was seen
      between patients with stable disease and age-matched controls. Serum HYA
      concentrations correlated significantly with the leukocyte count (rho = 0.38; P
      less than 0.02) and with the serum concentration of PIIINP (rho = 0.50; P less
      than 0.001). During cytotoxic treatment, the serum HYA and PIIINP concentrations
      decreased in concert with declining leukocyte counts. These findings suggest that
      clonal expansion is accompanied by a bone marrow stromal reaction similar to the
      repair processes following injury to soft connective tissues. The relatively
      modest changes in serum HYA with frequent overlaps between patient categories and
      healthy subjects imply that the clinical utility of single determinations of
      serum HYA in the present disease groups is restrained. On the other hand,
      sequential measurements of HYA may provide a reflection of the myeloproliferative
      process in individual patients.

PMID- 1984677
TI  - Evidence for the synthesis of embryonic globin chains in adult erythroid
      progenitor cells.
AB  - Embryonic globin chains were found to be synthesized in vitro by the BFU-E
      colonies derived from adult sickle cell anemia (SS) patients, their heterozygous
      relatives as well as a few normal controls. In the absence of sufficient material
      for conducting direct structural analyses of these peptides, they were confirmed
      by evaluating the co-migration of the epsilon and zeta-chains with the
      corresponding structurally characterized globin chains obtained from K562 cell
      lysates on a reversed phase high performance liquid chromatogram. The presence of
      zeta-chain was also confirmed using an immunologic procedure. Furthermore,
      significant 35S-methionine incorporation peak was observed corresponding to the
      zeta-chain synthesized by the BFU-E-derived colonies implying an active synthesis
      of this embryonic globin chain in BFU-E cells obtained from hemopoietically adult
      persons.

PMID- 1984678
TI  - Antithrombin III-Amiens: a new family with an Arg47----Cys inherited variant of
      antithrombin III with impaired heparin cofactor activity.
AB  - A family with an antithrombin III variant (AT-III-Amiens) demonstrating abnormal
      heparin cofactor activity is described. Amplification and direct sequencing of
      genomic DNA by the polymerase chain reaction procedure permitted the
      identification of an Arg47----Cys mutation in exon 2 of the variant antithrombin
      III gene.

PMID- 1984679
TI  - Clinical pharmacokinetics of a placenta-derived factor XIII concentrate in type I
      and type II factor XIII deficiency.
AB  - Limited data are available about the pharmacokinetics of placenta-derived factor
      XIII (FXIII) concentrate in patients with FXIII deficiency. This concentrate
      contains only the active subunit A but not the carrier subunit B of the factor,
      and perplexities have been raised about its clinical use. Moreover, no data are
      available on its use in the rare patients completely lacking both subunit A and
      subunit B. Therefore, we evaluated the pharmacokinetics of a commercial placenta
      concentrate in three patients with FXIII deficiency: two lacking subunit A (type
      II) and one lacking both subunits (type I). The elimination half-life of the
      infused placenta subunit A in the three patients was very similar (280, 283, and
      272 hr) and was also consistent with the previously reported data for plasma
      derived FXIII. No thrombin-independent activity was observed in our concentrate
      batches. The recovery was significantly lower in the type I patient, in whom
      infusion of subunit A was not able to elicit a monthly increment of subunit B, as
      usually observed in type II patients. Monthly infusions of placenta concentrate
      (at higher dosage in type I patient) have been administered to our patients for
      two to three years and no evidence of inhibitor against factor XIII activity has
      been observed. We conclude that placenta concentrates may be as effective as
      plasma derivatives in replacement therapy of factor XIII deficiency, even in
      patients who lack subunit B.

PMID- 1984680
TI  - Humoral immune responses to gag and env proteins from human immunodeficiency
      virus type 1 in hemophiliac patients.
AB  - Solid-phase enzyme immunoassays using recombinant gag and env proteins were
      developed to study humoral immune responses to HIV infection in a cohort of 105
      hemophiliac patients. Thirteen patients with ARC or AIDS and 92 asymptomatic
      patients were studied. A cross-sectional study showed a wide range of antibody
      responses to gag and env proteins; however, the differences between the ARC/AIDS
      and asymptomatic patients were statistically significant for both antigens (P
      less than .0004). In a longitudinal study, antibody levels in sera from 11
      asymptomatic patients with gag antibody log units less than or equal to 1.5 were
      compared to levels in sera from 10 ARC/AIDS patients and 8 asymptomatic patients
      with gag antibody greater than 1.5. These patient groups were followed for
      comparable periods of time (67.1-71.7 mo). The asymptomatic patients with low gag
      antibody and the ARC/AIDS patients showed a similar pattern of antibody response
      to gag protein overtime. In hemophiliac patients with HIV-1 infection a low titer
      of antibody to gag protein is not invariably associated with clinical
      deterioration and is not a useful serologic marker of impending progression to
      AIDS.

PMID- 1984681
TI  - Increased protein binding to a -530 mutation of the human beta-globin gene
      associated with decreased beta-globin synthesis.
AB  - Although some cases of the syndrome of hereditary persistence of fetal hemoglobin
      (HPFH) have been correlated with mutations causing a change in the binding of
      trans-acting factors to DNA sequences flanking the gamma-globin gene, this
      mechanism has not been described in beta-thalassemias upstream of the canonical
      promoter of the beta-globin gene. In this report we describe such a change in
      binding of a protein that may explain a silent carrier phenotype of beta
      thalassemia. We have previously demonstrated the binding of a protein (BP1)
      derived from a nuclear extract of human K562 cells to DNA 5' to the human beta
      globin gene in a region having a negative regulatory function. The binding of BP1
      in this region can be detected by DNAse I footprinting and by gel mobility shift
      analysis. We have now compared binding of BP1 to the normal sequence and a
      mutated sequence (+ATA/-T at -530 bp from the cap site) from the silent carrier
      of beta-thalassemia. Using mobility shift assays we show that BP1 binds about
      nine times more strongly to the mutated sequence than the normal sequence. These
      results suggest the possibility that the decreased expression of the beta-globin
      gene exhibited by the carrier may be due, at least in part, to tighter binding of
      a protein which functions as a negative control element or repressor.

PMID- 1984682
TI  - Maternal and fetal iron measurements in a hemochromatotic pregnancy.
AB  - The findings in the cord blood sample of an infant from a treated hemochromatotic
      mother of a raised transferrin saturation (88%) and a raised ferritin
      concentration (250.2 micrograms/L) together with elevated maternal values (66%
      and 91.6 micrograms/L, respectively) yet a normal total placental iron content
      (26.9 mg) suggested that in common with gastrointestinal mucosal cells and
      reticuloendothelial cells in hemochromatosis, the placental cell may exhibit an
      abnormality of iron storage and transport.

PMID- 1984683
TI  - Superwarfarin ingestion and detection.
AB  - Because of the emergence of warfarin resistance, new potent long-acting
      anticoagulants are now readily available in several over-the-counter rodenticide
      products. The availability of these "superwarfarin" compounds has led to
      accidental and purposeful human ingestions, one of which has resulted in a death.
      We summarize the prior case reports and report a second death. In addition, we
      report the availability of an assay to detect the presence of brodifacoum (a
      superwarfarin compound) in human plasma and tissues.

PMID- 1984684
TI  - Antiphospholipid antibodies and adrenal hemorrhage.
AB  - We recently encountered two cases of massive bilateral adrenal hemorrhage in
      patients with antiphospholipid antibodies. A search of the records of this
      institution covering the past 15 years revealed two additional patients with
      massive adrenal hemorrhage associated with evidence of antiphospholipid
      antibodies. Three of these four patients were receiving anticoagulant drug
      therapy. The presence of the antiphospholipid antibodies may increase the risk of
      massive adrenal hemorrhage, particularly in patients who receive anticoagulant
      drugs.

PMID- 1984685
TI  - Occurrence of high-grade T-cell lymphoma in a patient with Philadelphia
      chromosome-negative chronic myelogenous leukemia with breakpoint cluster region
      rearrangement: case report and review of the literature.
AB  - In this report, we describe a patient with Philadelphia chromosome-negative
      chronic myelogenous leukemia (CML) with breakpoint cluster region gene
      rearrangement who developed T-cell lymphoblastic lymphoma. The occurrence of T
      cell lymphoblastic lymphoma coincided with the appearance in the bone marrow of
      the cytogenetic abnormality, trisomy 22q11.2----22qter. This is the first report
      of high-grade T-cell lymphoma in a patient with documented CML.

PMID- 1984686
TI  - Acquired selective factor X deficiency in acute nonlymphocytic leukemia.
AB  - A case of acute nonlymphocytic leukemia (ANLL) and selective acquired FX
      deficiency at presentation is reported. The deficiency was not corrected by the
      infusion of fresh frozen plasma, but the patient's plasma had no neutralizing
      activity in vitro. The cause of the deficiency is unknown.

PMID- 1984687
TI  - Neutrophil alkaline phosphatase activity in the urinary neutrophils of a patient
      with chronic myelogenous leukemia.
AB  - We report here a patient with Philadelphia chromosome (Ph)-positive chronic
      myelogenous leukemia (CML) in chronic phase in whom the alkaline phosphatase
      activity of neutrophils in the peripheral blood was low while at the same time
      the alkaline phosphatase content of neutrophils present in the urine was
      elevated. This observation provides independent clinical support for the recent
      experimental finding that an extrinsic factor (granulocyte colony-stimulating
      factor) controls alkaline phosphatase expression in human neutrophils.

PMID- 1984688
TI  - Effective therapy of human immunodeficiency virus-associated anemia with
      recombinant human erythropoietin despite high endogenous erythropoietin.
AB  - A 32-year-old woman with human immunodeficiency virus (HIV) infection and
      progressive anemia presented to University Hospital with a hemoglobin of 3.4
      g/dl. Because of her religious beliefs, she refused transfusion, and no iron or
      vitamin deficiency was found. She responded to recombinant human erythropoietin
      150 U/kg intramuscularly thrice weekly with a rise in hemoglobin to 9.3 g/dl by 3
      months of treatment. The serum erythropoietin level before treatment was markedly
      elevated at 1,340 mU/ml.

PMID- 1984689
TI  - Thrombocytosis and erythropoietin-unresponsive anemia in patients with
      Castleman's disease.

PMID- 1984690
TI  - Granulocyte-macrophage colony-stimulating factor gene in myelodysplastic
      syndromes.

PMID- 1984691
TI  - Impaired production of burst promoting activity by blood mononuclear cells from
      chronic uremic patients.
AB  - The ability of blood mononuclear cells (MNC) to produce burst promoting activity
      (BPA) was evaluated in 31 patients with chronic renal failure. The BPA of cells
      from uremic patients, with or without hemodialysis, was consistently lower than
      that of 17 normal donors (mean 64%, P less than 0.01). Coculture of MNC with
      recombinant erythropoietin (rEpo) in vitro did not increase BPA production. Five
      of 31 patients received in vivo treatment with rEpo (1,500 units x3/week) and
      showed therapeutic benefit, but in all patients the BPA production remained low.
      On the other hand, in four patients who were on a hemodialysis protocol and
      subsequently underwent renal transplantation, impaired BPA production was
      resolved quickly, and at the same time the number of circulating BFU-E and the
      hemoglobin level increased toward normal ranges. Furthermore, such impaired BPA
      production was not observed in patients receiving continuous ambulatory
      peritoneal dialysis. These observations suggest that decreased production of BPA
      may play a role in the development of anemia associated with chronic uremic
      patients, and the correction of BPA production by the improvement of hemodialysis
      procedure may result in more effective therapy with rEpo for those patients.

PMID- 1984692
TI  - Reliability of a Standardized Mini-Mental State Examination compared with the
      traditional Mini-Mental State Examination.
AB  - OBJECTIVE: The objective of this study was to compare the reliability of the Mini
      Mental State Examination with that of a new Standardized Mini-Mental State
      Examination, which has expanded guidelines for administration and scoring.
      METHOD: The subjects were 32 stable elderly residents of a nursing home and 16
      elderly residents of a chronic care hospital unit. Six raters administered the
      Folstein Mini-Mental State to 22 of these stable elderly subjects, and five
      raters administered the standardized version to 26 of these subjects. Each
      subject was tested on three different occasions 1 week apart. Each rater tested 4
      6 subjects at the first and third weeks and 4-6 different subjects at the second
      week. The analytic technique used was one-way analysis of variance to estimate
      the interrater variance and the intrarater variance. RESULTS: The intrarater
      variance on all occasions was reduced by 86% and the interrater variance was
      reduced by 76% when the Standardized Mini-Mental State was used; the reductions
      in variance were significant (p less than 0.003). The intraclass correlation for
      the Mini-Mental State was 0.69; for the standardized version it was 0.90. It took
      less time to administer the Standardized Mini-Mental State than the Mini-Mental
      State. CONCLUSIONS: The Standardized Mini-Mental State had better reliability
      than the Mini-Mental State in this study group. Although the improved reliability
      of the Standardized Mini-Mental State was achieved by reducing measurement noise,
      this advantage would likely occur in a broad spectrum of patients.

PMID- 1984693
TI  - Neuropsychological testing of patients with borderline personality disorder.
AB  - OBJECTIVE AND METHOD: This study examined whether a battery of neuropsychological
      tests could detect cognitive deficits--particularly in the areas of perception,
      learning, and memory--in patients with borderline personality disorder. The test
      battery was completed by 16 research outpatients with borderline personality
      disorder, typified by behavioral dyscontrol and diagnosed according to DSM-III-R
      criteria and the Diagnostic Interview for Borderline Patients. A comparison group
      of 16 normal volunteers also completed the test battery. RESULTS: The performance
      of the borderline patients was significantly impaired in comparison with that of
      the normal group on memory tests requiring uncued recall of complex, recently
      learned material. Cues given on an auditory memory task partially corrected that
      deficit. The patients' performance was also significantly impaired on several
      visual perceptual tests. These deficits do not appear to have been attributable
      to attentional problems, psychomotor impairment, current major depression, or
      history of alcohol abuse. CONCLUSIONS: The observed difficulties in separating
      essential from extraneous visual information and in recalling complex material
      may be relevant in understanding some of the clinical features of borderline
      personality disorder. The observed memory improvement resulting from cueing
      suggests specific strategies that may be used to aid patients' recall of complex
      material.

PMID- 1984694
TI  - A family-genetic study of girls with DSM-III attention deficit disorder.
AB  - OBJECTIVE: The authors evaluated family-genetic risk factors in girls with
      attention deficit disorder and compared these results to findings in the authors'
      previous study of boys with attention deficit disorder. METHOD: Twenty-one girls
      with attention deficit disorder and 20 normal comparison girls were consecutively
      ascertained from a pool of existing and new referrals from a pediatric
      psychopharmacology unit and a medical pediatric unit of the same urban hospital.
      First-degree relatives of the attention deficit disordered girls (N = 69) and of
      the normal girls (N = 71) were also assessed. Both groups of girls and their
      relatives were evaluated on the basis of structured diagnostic interviews
      conducted by raters who were blind to the clinical status of the probands.
      RESULTS: The relatives of the girls with attention deficit disorder had higher
      risks for attention deficit disorder, antisocial disorders, major depression, and
      anxiety disorders. The higher risk for attention deficit disorder could not be
      accounted for by gender or generation of relative, age of proband, social class,
      or family intactness. These findings are highly consistent with the findings in
      the authors' previous study of boys with attention deficit disorder, which was
      conducted with identical methods. CONCLUSIONS: This study provides further
      support for the validity of the diagnosis of attention deficit disorder in girls
      and suggests that the genders share a common biological substrate.

PMID- 1984695
TI  - Axis II comorbidity in substance abusers.
AB  - OBJECTIVE: To assess the complex relationship between substance abuse and
      personality disorders, the authors determined the prevalence of personality
      disorders in a group of middle-class substance abusers and compared the subjects
      who had personality disorders with those who did not. METHOD: The subjects were
      drawn from patients consecutively admitted to an inpatient substance abuse
      program in a private psychiatric hospital; they were the first 100 who agreed to
      participate. Substance dependence was diagnosed according to DSM-III-R, and the
      patients were assessed with the Structured Clinical Interview for DSM-III-R
      Personality Disorders, Alcohol Use Inventory, MMPI, Health and Daily Living Form,
      Shipley Institute of Living Scale, and measures of chemical use and life
      satisfaction. RESULTS: Of the 100 substance abusers, 57 had personality
      disorders. These patients differed significantly from the 43 patients without
      personality disorders in several ways: they had greater involvement with illegal
      drugs, had different patterns of alcohol use, had greater psychopathology, were
      less satisfied with their lives, and were more impulsive, isolated, and
      depressed. CONCLUSIONS: Because of the marked differences between the substance
      abusers with and without personality disorders, a uniform approach to substance
      abuse treatment may be inadequate.

PMID- 1984696
TI  - Controlled comparison of buspirone and clomipramine in obsessive-compulsive
      disorder.
AB  - Eighteen outpatients with obsessive-compulsive disorder were treated with either
      buspirone, a partial serotonin agonist, or clomipramine, a serotonin uptake
      inhibitor, in a double-blind, random-assignment study. Both drugs led to
      statistically significant and similar improvements in scores on the Yale-Brown
      Obsessive-Compulsive Rating Scale and other obsessive-compulsive and depression
      scales. This preliminary result warrants further exploration with a larger sample
      and other serotonergic agents.

PMID- 1984697
TI  - Comments on the Klerman-Stone debate on Osheroff v. Chestnut Lodge.

PMID- 1984698
TI  - A case of recurrent premenstrual psychosis.

PMID- 1984699
TI  - Iron overload in psychiatric illness.

PMID- 1984700
TI  - Hypothesis about borderline personality disorder.

PMID- 1984701
TI  - Effects of gun laws on suicide rates.

PMID- 1984702
TI  - A prospective comparison of four insanity defense standards.
AB  - OBJECTIVE: Controversy about the formulation of the insanity defense has been
      intense, but little empirical work is available regarding how different standards
      affect court findings. The major aims of the present study were to determine if
      different standards for determining insanity produced different judgments and to
      provide a broad descriptive picture of those cases in which the standards
      appeared to make a difference. METHOD: Four forensic psychiatrists were asked to
      indicate whether they thought 164 defendants met any or all of four insanity
      tests: 1) the American Law Institute (ALI) cognitive criterion, 2) the ALI
      volitional criterion, 3) the APA test, and 4) the M'Naghten rule. RESULTS: The
      four psychiatrists determined that 97.5% of the defendants met the ALI volitional
      criterion, 73.9% met the APA criterion, 70.3% met the M'Naghten rule, and 69.5%
      met the ALI cognitive criterion. Nearly two-thirds of the defendants met all four
      insanity tests, and 24.4% met only the ALI volitional test. Few defendants met
      cognitive tests without also meeting the ALI volitional test. Elimination of the
      volitional test for insanity reduced the rate of psychiatric recommendations of
      acquittal by 24.4%. CONCLUSIONS: These findings highlight the fact that the
      primary logical division between volitional and cognitive standards appears to be
      powerful but that distinctions between types of cognitive standards are not
      terribly powerful. In addition, the variation among individual raters must be
      viewed as an important determinant of how any insanity standard is applied.

PMID- 1984704
TI  - Somatization: a spectrum of severity.
AB  - OBJECTIVE: The DSM-III-R diagnosis of somatization disorder requires that a
      patient have a specific number of medically unexplained somatic symptoms. This
      number of symptoms was developed by committee consensus, and it is not clear
      whether patients with this specific number of symptoms can be differentiated from
      patients with lower but still substantial numbers of somatic symptoms. METHOD:
      Fifty-one percent of 767 high utilizers of two primary care clinics were
      identified as distressed by an elevated SCL anxiety, depression, or somatization
      scale score or by their primary care physician. The Diagnostic Interview Schedule
      (DIS) was completed on 119 distressed high utilizers who were randomly assigned
      to an intervention group in a controlled trial of psychiatric consultation. The
      119 distressed high utilizers were separated into four categories according to
      the number of unexplained somatic symptoms found on the DIS and were compared on
      demographic, psychiatric distress, disability, medical, and health utilization
      variables. RESULTS: The data suggest that many clinical and behavioral features
      of somatization are significantly more common in patients with four to 12
      medically unexplained somatic symptoms rather than changing dramatically at the
      diagnostic threshold for somatization disorder. The data also showed that
      patients who meet the DSM-III-R criteria for somatization disorder are severely
      ill and have a high burden of psychiatric illness and disability. CONCLUSIONS:
      The results suggest that the DSM-IV somatoform disorders section should include
      somatization disorder, an abridged definition of somatization disorder often
      associated with anxiety and depression, as well as a type of somatization
      associated with an adjustment disorder.

PMID- 1984703
TI  - Decision making in psychiatric civil commitment: an experimental analysis.
AB  - OBJECTIVE: Legislation in Canada and the United States that was intended to
      decrease the use of civil commitment has resulted in a paradoxical increase in
      involuntary hospital admissions. To elucidate the reasons for this increase, this
      study was designed to assess the relative importance of various factors involved
      in the decision to commit a patient. METHOD: All psychiatrists in Ontario were
      sent a questionnaire asking them to make commitment decisions based on
      hypothetical case vignettes. Four factors were systematically varied in the
      vignettes: the patients' legal commitability, clinical treatability, alternative
      resources, and psychotic symptoms. Completed questionnaires, with three vignettes
      each, were returned by 495 respondents. RESULTS: All four variables were
      statistically significant in the expected direction; legal commitability (i.e.,
      dangerousness to self and/or others, inability to care for self) and presence of
      psychotic symptoms accounted for the majority of the variance in the final
      decision to commit. CONCLUSIONS: These results suggest that psychiatrists in
      Ontario rely primarily on legally mandated factors (i.e., psychosis and
      dangerousness) in making their decisions to commit, although a considerable
      amount of individual variation is also evident.

PMID- 1984705
TI  - Family interactions within incest and nonincest families.
AB  - OBJECTIVE: The study addressed the questions, What are the interactional patterns
      in families in which incest occurs? and Do these patterns differ from those of
      families with other clinical problems? METHOD: The families for the study were
      chosen from two outpatient clinics; the C. Henry Kempe, National Center for the
      Prevention and Treatment of Child Abuse and Neglect provided access to families
      with incest, and the nonincest families each had a child seen in a university
      child psychiatry clinic. In each of these settings, 30 families were selected in
      the order of referral for evaluation. All families agreed to participate. Each
      family was given two tasks to perform during a structured interview. The
      interviews were videotaped, and 15-20-minute segments were rated independently by
      two of the authors, who used the Beavers-Timberlawn Family Evaluation Scale to
      assess interactional behaviors within each family. RESULTS: The incest families
      were significantly more dysfunctional in all but one area of family interaction.
      The distribution of power within a family did not differentiate the two types of
      families. CONCLUSIONS: The incest families dysfunctional patterns that seemed to
      support and maintain the incestuous behavior were a rigid family belief system, a
      dysfunctional parental coalition, parental neglect and emotional unavailability,
      and the inability to nurture autonomy in family members.

PMID- 1984706
TI  - Dissociation and childhood trauma in psychologically disturbed adolescents.
AB  - OBJECTIVE: To test the hypothesis that dissociation in adolescence is positively
      correlated with stress or abuse experienced earlier, the authors assessed
      dissociation in a heterogeneous group of disturbed adolescents and examined the
      relationship between the degree of dissociation and the degree of reported
      childhood stress, abuse, or trauma. METHOD: The subjects were 47 adolescents, 13
      17 years old, who were institutionalized for periods of 1-13 weeks in a private
      mental hospital; 35 were girls and 12 were boys. Participants completed the
      Dissociative Experiences Scale and a child abuse and trauma questionnaire. The
      hospital records of 40 of the 47 adolescents were also available. RESULTS: Scores
      on the Dissociative Experiences Scale correlated significantly with self-reported
      physical abuse or punishment, sexual abuse, psychological abuse, neglect, and
      negative home atmosphere but not with abuse ratings made from hospital records.
      CONCLUSIONS: Together with the authors' previous work showing a relation between
      childhood stress and later dissociation in normal college students, these
      findings support the view that dissociation represents a reaction to early
      negative experience and places multiple personality disorder at the extreme end
      of a continuum of dissociative sequelae of childhood trauma. Researchers should
      continue to try to identify psychiatric patients with prominent dissociative
      characteristics or symptoms and attempt to correlate this phenomenology with
      negative earlier experiences.

PMID- 1984707
TI  - Psychiatric morbidity in adult inpatients with childhood histories of sexual and
      physical abuse.
AB  - OBJECTIVE: To extend the knowledge on long-term effects of childhood abuse in
      psychiatric patients to a large sample, the authors explored childhood sexual and
      physical abuse in adult inpatients over 1,040 consecutive admissions. METHOD: The
      947 patients were admitted to a tertiary-care military medical center. Each
      patient was interviewed, and abuse history, DSM-III-R diagnosis, and other
      characteristics were recorded. RESULTS: The prevalence of reported childhood
      abuse was 18% overall: 9% for sexual abuse (with or without physical abuse), 10%
      for physical abuse (with or without sexual abuse), and 3% for combined abuse.
      More female than male patients reported abuse. Alcohol use disorders were more
      common in victims of physical or combined abuse than in sexually abused or
      nonabused patients. Axis II diagnoses, particularly borderline personality
      disorder, were more frequent in abuse victims than in nonabused patients.
      Histories of drug and alcohol abuse were more common in patients reporting
      physical or combined abuse than in nonabused patients. Suicidality was also more
      frequent in abused than nonabused inpatients and was noted in 79% of the patients
      with histories of combined abuse. Combined abuse in women and physical abuse in
      men were associated with a family history of psychiatric illness, most commonly
      alcoholism in male relatives. CONCLUSIONS: These findings emphasize the need for
      greater attention to family dynamics, aggressive diagnosis and treatment of
      alcoholism within the family, and, especially, determination of patients' abuse
      histories, even if repeated questioning is necessary.

PMID- 1984708
TI  - Sleep disturbances in survivors of the Nazi Holocaust.
AB  - OBJECTIVE AND METHOD: Sleep disturbances are commonly reported by victims of
      extraordinary stress and can persist for decades. This study was designed to test
      the hypothesis that survivors of the Nazi Holocaust would have significantly more
      and different sleep problems than depressed and healthy comparison subjects and
      that the severity of the survivors' problems would be correlated with length of
      time spent in a concentration camp. Forty-two survivors, 37 depressed patients,
      and 54 healthy subjects of about the same age, all living in the community,
      described their sleep patterns over the preceding month on the Pittsburgh Sleep
      Quality Index, a self-rating instrument that inquires about quality, latency,
      duration, efficiency, and disturbances of sleep, use of sleep medication, and
      daytime dysfunction. RESULTS: The survivors had significantly greater sleep
      impairment than the healthy comparison subjects, as measured by all subscales of
      the index, but had less impairment than the depressed patients except on the
      sleep disturbances and daytime dysfunction subscales. However, for specific items
      within these subscales, survivors had significantly more frequent awakenings due
      to bad dreams and had less loss of enthusiasm than the depressed subjects. Sleep
      disturbances and frequency of nightmares were significantly and positively
      correlated with the duration of the survivors' internment in concentration camps.
      CONCLUSIONS: These findings suggest that for some Holocaust survivors, impaired
      sleep and frequent nightmares are considerable problems even 45 years after
      liberation.

PMID- 1984709
TI  - Cognitive deficits and psychopathology among former prisoners of war and combat
      veterans of the Korean conflict.
AB  - OBJECTIVE: This study was conducted to describe the long-term psychological and
      psychiatric sequelae of prisoner of war (POW) confinement against the backdrop of
      psychiatric evaluations of Korean conflict repatriates more than 35 years ago.
      METHOD: A group of 22 POWs and a group of 22 combat veteran survivors of the
      Korean conflict were compared on measures of problem solving, personality
      characteristics, mood states, and psychiatric clinical diagnoses by means of a
      battery of psychometric instruments and structured clinical interviews. RESULTS:
      Although the two groups were similar in background and personal characteristics,
      they differed in reports of life adjustment problems, complaints of physical
      distress, proficiency on cognitive tests, objectively measured personality
      characteristics, and assigned psychiatric diagnoses. CONCLUSIONS: Illustrated by
      a case report which describes the prolonged brutality of the Korean conflict POW
      experience for one individual, the results suggest that the psychiatric symptoms
      documented more than three decades ago have persisted in severity and chronicity.
      In addition to problems with cognitive deficits and complaints of bodily
      discomfort, most common among POW survivors were symptoms of suspiciousness,
      apprehension, confusion, isolation, detachment, and hostility.

PMID- 1984710
TI  - Effects of buspirone and alprazolam on the cognitive performance of normal
      elderly subjects.
AB  - OBJECTIVE: To increase understanding of the potential in elderly persons for
      disability related to behavioral side effects of anxiolytic medications,
      cognitive and psychomotor effects of clinical doses of buspirone and a popular
      intermediate-acting benzodiazepine, alprazolam, were examined in carefully
      screened, healthy elderly subjects. METHOD: Sixty subjects recruited through
      community organizations and newspaper advertisements and screened on the basis of
      history, physical examination, and laboratory studies were randomly assigned to
      one of three drug treatment groups. After 2 days of washout placebo, subjects
      were given 0.25 mg t.i.d. of alprazolam, 5 mg t.i.d. of buspirone, or placebo
      three times a day for a total of 14 days in a double-blind design. Behavioral
      assessments were completed beginning 1 hour after ingestion of medication on the
      second washout placebo day, day 1 of the treatment period, and day 14 of the
      treatment period. Tests included the continuous performance test, recall memory
      for word lists, digit-symbol substitution, retention of pictorial stimuli over 1
      hour, the Profile of Mood States, and subjective ratings of mental status.
      RESULTS: Buspirone did not affect reaction time, vigilance, psychomotor speed, or
      memory function. Alprazolam had minimal effects on vigilance, psychomotor speed,
      and memory on the first treatment day and had no effects after repeated doses.
      CONCLUSIONS: Buspirone did not produce behavioral side effects that could lead to
      disability, and alprazolam had minimal side effects. Because the patients were
      carefully screened, it is unclear whether these medications in the doses used
      would have more side effects in less healthy elderly patients.

PMID- 1984711
TI  - Cognitive and behavioral effects of the coadministration of dextroamphetamine and
      haloperidol in schizophrenia.
AB  - OBJECTIVE: The authors sought to determine if an acute dose of dextroamphetamine
      might have positive effects on affect and cognition in schizophrenic patients
      maintained on a regimen of haloperidol and, if so, what variables might predict
      such improvements. METHOD: Twenty-one patients with chronic schizophrenia who
      were hospitalized on a research ward received a single oral dose of
      dextroamphetamine (0.25 mg/kg) in a double-blind, placebo-controlled, crossover
      study. All patients were receiving 0.4 mg/kg per day of haloperidol. Cognitive
      tests, motor tests, global ratings, mood ratings, and videotape ratings were used
      to determine the effect of the coadministration of these drugs. Ventricle-brain
      ratios derived from CT scans were used to predict response to the
      coadministration of these drugs. RESULTS: Amphetamine improved performance on a
      measure of concept formation on the Wisconsin Card Sorting Test but did not
      result in changes in performance on tests of memory or attention. As a group, the
      patients were more active and performed psychomotor tests more quickly while
      receiving amphetamine. Six patients were judged by clinical raters to have
      improved in terms of affect, cooperation, and engagement with the environment.
      Improvement was associated with enlarged cerebral ventricles and increases in
      blink rate from the placebo to the active drug condition. No patient
      unequivocally worsened. CONCLUSIONS: These results may be consistent with the
      theory that coadministration of amphetamine and haloperidol produces relatively
      selective enhancement of cortical dopaminergic activity. However, because of the
      acute nature of the trial and the specialized research environment in which it
      was conducted, the authors do not advocate amphetamine as a routine clinical
      treatment of schizophrenia.

PMID- 1984712
TI  - Christian Psychiatry: the impact of evangelical belief on clinical practice.
AB  - OBJECTIVE: The authors surveyed psychiatrists in the Christian Psychiatry
      movement to assess the role of religious belief in their practices. METHOD: The
      psychiatrists were members of the Christian Medical and Dental Society;
      questionnaires were sent to 260, and usable responses were received from 193. The
      subjects were asked about demographic and practice variables, "born again"
      religious experiences, group cohesion, and beliefs about using the Bible and
      prayer in treatment. RESULTS: The respondents were somewhat more religious than
      Americans overall, who are themselves more religious than most psychiatrists.
      Nearly all reported having been "born again," after which they generally
      experienced a decrease in emotional distress. There was a significant difference
      in the respondents' affiliative feelings toward psychiatrists in the Christian
      Psychiatry movement and other psychiatrists. For acute schizophrenic or manic
      episodes, the respondents considered psychotropic medication the most effective
      treatment, but they rated the Bible and prayer more highly for suicidal intent,
      grief reaction, sociopathy, and alcoholism. Whether or not a patient was
      "committed to Christian beliefs" made a significant difference in whether the
      respondents would recommend prayer to the patient as treatment. About one-half
      said they would discourage strongly religious patients from an abortion,
      homosexual acts, or premarital sex, and about one-third said they would
      discourage other patients from these activities. CONCLUSIONS: Many studies have
      suggested a need for more sensitivity to religious issues by psychiatrists, and
      this study provides systematic findings on one approach. It remains important to
      evaluate ways in which a religious perspective can be related to clinical
      practice and what benefits and problems may derive from such a relationship.

PMID- 1984713
TI  - How do HMOs reduce outpatient mental health care costs?
AB  - OBJECTIVE: Because previous studies of differences in utilization of mental
      health care services have had important limitations, it is not clear if their
      findings that health maintenance organization (HMO) outpatient mental health care
      costs less than fee-for-service care are due to less access, less intensive care
      per user, or selective enrollment of healthier people by HMOs. Therefore, the
      authors used data from the National Institute of Mental Health Epidemiologic
      Catchment Area (ECA) study to examine differences in the prevalence of
      psychiatric disorder and differences in the use of outpatient mental health
      services for adults enrolled in HMO or fee-for-service health insurance plans.
      METHOD: The subjects were an ECA community sample obtained from East Los Angeles
      and West Los Angeles. This sample included a large number of Hispanic subjects.
      The subjects were categorized according to their responses to a 5-item battery on
      insurance as Medicare enrolles, members of private fee-for-service plans,
      Medicaid enrollees, members of an HMO, and uninsured. The presence or absence of
      psychiatric disorders was determined by using the NIMH Diagnostic Interview
      Schedule. Both users and nonusers of mental health services were studied.
      RESULTS: The HMO and fee-for-service plans had similar prevalence of psychiatric
      disorder and similar access to specialty mental health care. However, HMO
      enrollees had significantly fewer visits per user to providers of specialty care.
      CONCLUSIONS: The most likely explanation for lower mental health care costs in
      HMOs is a less intensive style of care for a comparably sick population.

PMID- 1984714
TI  - Guidelines for combined emergency medicine-internal medicine residency training
      programs. American Board of Emergency Medicine.

PMID- 1984715
TI  - Venous pressure gradients during CPR: 'yes, Virginia, veins have valves!'.

PMID- 1984716
TI  - TAC use and absorption of cocaine.

PMID- 1984717
TI  - TAC toxicity in the emergency department.

PMID- 1984718
TI  - Recommendations for monitoring intracranial pressure.

PMID- 1984719
TI  - Stat RPRs.

PMID- 1984720
TI  - Faculty attrition among three specialties.
AB  - STUDY OBJECTIVES: To survey faculty attrition in emergency medicine and compare
      it with faculty attrition in the specialties of orthopedic surgery and
      cardiology. DESIGN: Chairmen of the three departments were surveyed regarding
      faculty attrition, work hours, and motivation for leaving. Those emergency
      physicians having left also were surveyed. MAIN RESULTS: Responses were obtained
      from 67 of 68 emergency medicine programs, 53 of 58 orthopedic programs, and 47
      of 54 cardiology programs. Overall, there were 670 total faculty in emergency
      medicine, of which 67 (10%) left their positions during 1988-38 to enter private
      practice, 18 to take another academic position, and 11 to do something
      unidentified. There was no difference in faculty attrition among the three
      specialties or in what the physicians left to do (P = .75). Both the orthopedists
      and the cardiologists worked more total hours each week (P = .001) but fewer
      night hours (P = .03) than the emergency physicians. Among the 67 emergency
      medicine programs, 28 reported no attrition; 39 reported one or more physicians
      leaving the program. These two groups of programs did not differ in terms of
      faculty size, hours worked, or night hours worked.

PMID- 1984721
TI  - Rational ordering of electrolytes in the emergency department.
AB  - STUDY OBJECTIVE: To validate the predictive abilities of a retrospectively
      developed set of clinical criteria for detecting clinically significant
      electrolyte abnormalities, using a different patient population. DESIGN: Cross
      sectional study. SETTING: The emergency department of a busy public hospital.
      TYPE OF PARTICIPANTS: Nine hundred eighty-two patients on whom the emergency
      physician ordered serum electrolytes. INTERVENTIONS: The predictive properties of
      ten clinical criteria were evaluated; these included poor oral intake, vomiting,
      chronic hypertension, taking a diuretic, recent seizure, muscle weakness, age of
      65 years or more, alcoholism, abnormal mental status, and recent history of
      electrolyte abnormality. MEASUREMENTS AND MAIN RESULTS: Seven hundred thirty
      patients (74.3%) had one or more electrolytes outside of the laboratory normal
      range, but only 143 (14.6%) had clinically significant electrolyte abnormalities.
      The clinical criteria predicted 135 of the clinically significant electrolyte
      abnormalities (sensitivity, 94.4%). When the eight "false-negative" cases were
      reviewed, none of the electrolyte abnormalities affected patient outcome.
      Implementation of the criteria would have avoided unnecessary testing in 233
      patients (23.7%). CONCLUSION: Although no set of clinical criteria can eliminate
      the need for clinical judgment, use of a set of clinical criteria could
      substantially decrease electrolyte ordering without compromising patient care.

PMID- 1984722
TI  - High-dose epinephrine improves outcome from pediatric cardiac arrest.
AB  - STUDY OBJECTIVE: Animal studies suggest that the standard dose of epinephrine
      (SDE) for treatment of cardiac arrest in human beings may be too low. We compared
      the outcome after SDE with that after high-dose epinephrine (HDE) in children
      with refractory cardiac arrest. DESIGN: Prospective intervention versus historic
      control groups. TYPE OF PARTICIPANTS: Two similar groups of 20 consecutive
      patients each (median ages, 2.5 and 3 years) with witnessed cardiac arrest who
      remained in arrest after at least two SDEs (0.01 mg/kg). INTERVENTIONS: Treatment
      with an additional SDE versus HDE (0.2 mg/kg). MEASUREMENTS AND MAIN RESULTS: The
      rates of return of spontaneous circulation and long-term survival were compared.
      Fourteen of the HDE group (70%) had return of spontaneous circulation, whereas
      none of the SDE group did (P less than .001). Eight children survived to
      discharge after HDE, and three were neurologically intact at follow-up. No
      significant toxicity from HDE was observed. CONCLUSION: HDE provided a higher
      return of spontaneous circulation rate and a better long-term outcome than SDE in
      our series of pediatric cardiac arrest. HDE may warrant incorporation into
      standard resuscitation protocols at an early enough point to prevent irreversible
      brain injury.

PMID- 1984723
TI  - Right atrial-jugular venous pressure gradients during CPR in children.
AB  - OBJECTIVE: This study measured the internal jugular vein and right atrium
      pressures during pediatric CPR to detect and quantify venous pressure gradients
      across the thoracic inlet. DESIGN: Ten children from 2 months to 15 years old who
      underwent CPR had simultaneous pressure measurements recorded from the right
      atrium and jugular vein. RESULTS: The right atrium-jugular vein peak compression
      phase gradient was 18.3 +/- 4.7 mm Hg (mean +/- SD), and the end-relaxation
      gradient was 0.7 +/- 0.6. Jugular vein pressure exceeded the right atrium only in
      the early-relaxation phase (right atrium-jugular vein = -2.1 +/- 1.2). Thoracic
      inlet venous valving persisted throughout the duration of CPR. CONCLUSION: There
      is a large venous gradient across the thoracic inlet during chest compressions in
      children, facilitating cerebral blood flow. This gradient reversed only in the
      early-relaxation phase. The data suggest that jugular venous return occurs only
      in the early-relaxation phase, whereas cerebral venous drainage persists
      throughout the CPR cycle.

PMID- 1984724
TI  - A prospective analysis of intramuscular meperidine, promethazine, and
      chlorpromazine in pediatric emergency department patients.
AB  - STUDY OBJECTIVE: To examine physiologic responses and efficacy of 2, 1, and 1
      mg/kg IM meperidine, promethazine, and chlorpromazine (MPC), respectively, in
      children. DESIGN: Prospective, unblinded trial. SETTING: A university and
      community emergency department. PATIENTS: Sixty-three hemodynamically and
      neurologically stable children. INTERVENTION: Single dose of IM MPC. MEASUREMENTS
      AND MAIN RESULTS: Serial respirations, heart rate, arterial systolic blood
      pressure, oxygen saturation, and Glasgow Coma Scale were measured at 30-minute
      intervals. Effectiveness was assessed by two independent observers using separate
      visual analog scales for cooperation and sedation. Times to sleep (27 +/- 24
      minutes), sitting upright (103 +/- 87 minutes), ED discharge (4.7 +/- 2.4 hours),
      eating (11 +/- 7.9 hours), and normal behavior (19 +/- 15 hours) were acceptable.
      Minor, but statistically significant, changes in respiration rate (-1.9 +/- 0.4),
      heart rate (+4.5 +/- 1.8), oxygen saturation (-0.7 +/- 0.3%), and Glasgow Coma
      Scale (-2.5 +/- 0.6) occurred for 120 minutes after MPC. No serious complications
      or resuscitation were required. Mean visual analog scale scores were 5.0/10.4 or
      more in 71% of cases, with interobserver agreement very good (cooperation, r =
      .79; effectiveness, r = .80). Twenty-nine percent of children were judged
      insufficiently sedated. CONCLUSION: IM MPC is a safe and generally effective
      agent for ED procedures in selected children.

PMID- 1984725
TI  - Acute phase reactants and risk of bacterial meningitis among febrile infants and
      children.
AB  - STUDY OBJECTIVE: To test the hypothesis that quantitation of either C-reactive
      protein (CRP) or the total peripheral WBC count can improve clinical detection of
      underlying bacterial meningitis among young febrile children. DESIGN: Cross
      sectional survey of selected symptoms of central nervous system infection, signs
      of meningeal irritation and/or elevated intracranial pressure, levels of CRP in
      serum, and total peripheral WBC counts among unselected pediatric patients
      undergoing lumbar punctures for evaluation of acute febrile illnesses. SETTING:
      Emergency department and acute care "walk-in" clinic of an urban, university
      affiliated general hospital. PARTICIPANTS: 160 previously well, acutely febrile
      infants and children (median age, 6 months). RESULTS: The prevalence of bacterial
      meningitis was 6%. Sensitivity of symptoms was 1.00 and specificity was 0.17.
      Sensitivity of signs was 0.70 and specificity was 0.81. Of the acute phase
      reactants, sensitivity of a CRP level of more than 1.0 mg/dL was 0.80, while that
      of a total peripheral WBC count of more than 15,000/mm3 was 0.40. The presence of
      signs and/or a CRP level of more than 1.0 mg/dL correctly identified all children
      with bacterial meningitis (sensitivity, 1.00). The absence of signs and a CRP
      level of 1.0 mg/dL or less correctly identified 71 of 150 children without
      bacterial meningitis (specificity, 0.47). Of 125 children without meningeal
      signs, the combination of symptoms and a CRP level of more than 1.0 mg/dL
      correctly identified all three children with bacterial meningitis (sensitivity,
      1.00). The absence of these symptoms and/or a CRP level of 1.0 mg/dL or less
      correctly identified 80 of 122 children without bacterial meningitis
      (specificity, 0.66). CONCLUSION: Quantitation of CRP but not the total peripheral
      WBC count can increase the sensitivity of physical examination findings and the
      specificity of symptoms for the diagnosis of bacterial meningitis. Measurement of
      CRP in serum is useful as an adjunct to history and physical examination for the
      detection of acute bacterial meningitis in the acutely febrile child.

PMID- 1984726
TI  - Comparison of rectal, axillary, and tympanic membrane temperatures in infants and
      young children.
AB  - STUDY OBJECTIVE: To evaluate the reliability of a tympanic membrane thermometer
      in detecting fever in young children presenting to the emergency department.
      SETTING: Pediatric emergency department in an urban teaching hospital,
      DESIGN/MEASUREMENT/PARTICIPANTS: Temperature measurements were obtained
      sequentially at three body sites in children less than 3 years old presenting to
      the pediatric ED. Axillary and rectal temperatures were obtained with an
      electronic thermistor probe (Diatek 500), and tympanic membrane temperatures were
      obtained with a noncontact, infrared sensing device (First TEMP). Patients were
      stratified by age, ear canal patency, presence of otitis media, and rectal
      temperature. RESULTS: Of 224 patients enrolled, 87 (39%) were febrile. Overall
      correlation of axillary and tympanic membrane measurements to rectal for all
      strata was .75 (P = .001) and .81 (P = .001), respectively. Sensitivity in
      detecting fever for axillary and tympanic membrane sites was .48 and .55,
      respectively. Otitis media and ear patency did not influence correlation of
      tympanic membrane measurements. Low tympanic membrane temperature sensitivity may
      be a result of probe configuration. CONCLUSION: Tympanic membrane and axillary
      temperatures should be viewed with caution in children less than 3 years old as
      neither can detect fever reliably.

PMID- 1984728
TI  - Evaluation and management of supraventricular tachycardia in children.
AB  - Emergency physicians may be called on to resuscitate acute complications in
      pediatric patients with congenital heart disease. Supraventricular tachycardia,
      with or without hemodynamic decompensation, is one of the most serious
      complications. We present the case of a 22-month-old boy with a history of single
      ventricle who presented to our institution with a history of syncope and
      hemodynamically stable supraventricular tachycardia. Initial attempts at
      pharmacologic conversion with propranolol and verapamil failed. The arrhythmia
      was terminated in response to an IV fluid bolus and dopamine infusion and
      probably resulted from a combination of anemia, hypovolemia, and impaired
      contractility. Appropriate evaluation and management relating to the cre of acute
      supraventricular tachycardia in children are discussed.

PMID- 1984727
TI  - Clinical features of misdiagnosed appendicitis in children.
AB  - STUDY OBJECTIVE: To compare clinical features of children with misdiagnosed
      appendicitis with those of children with appendicitis initially diagnosed
      correctly. DESIGN: Retrospective review of hospital, emergency department, and
      clinic records. SETTING: University medical center with annual ED census of
      40,000 patients. PARTICIPANTS: Children less than 13 years old admitted between
      May 1, 1979, and April 30, 1989, with a discharge diagnosis of appendicitis.
      MEASUREMENTS: Records were reviewed for historical, physical examination,
      laboratory, and pathologic features for all patients on their initial
      presentation to a physician and on final presentation during which the correct
      diagnosis was made. Using chi 2 analysis and Student's test, clinical features of
      misdiagnosed patients and patients diagnosed correctly were compared. RESULTS:
      One hundred eighty-one cases were identified with 50 initially misdiagnosed. On
      initial presentation, misdiagnosed patients were younger and more likely to have
      vomiting before pain onset, constipation, diarrhea, dysuria, and signs and
      symptoms of upper respiratory infections. Misdiagnosed cases were less likely to
      have right lower quadrant tenderness and documentation of bowel sounds,
      peritoneal signs, and rectal examinations. On final presentation, misdiagnosed
      patients were more likely to have pain duration of more than two days,
      temperature of more than 38.3 C, and to appear lethargic and irritable (P less
      than .05 for all measurements). CONCLUSION: Clinical features of children with
      misdiagnosed appendicitis differ from those of children with appendicitis
      initially diagnosed correctly.

PMID- 1984729
TI  - Systemic atropine administration during cardiac arrest does not cause fixed and
      dilated pupils.
AB  - OBJECTIVES: Systemic administration of atropine during CPR may postpone brain
      death determination because of its reputed ability to produce fixed and dilated
      pupils. We studied the effect of atropine administered in the usual doses as an
      adjunct to endotracheal intubation and for cardiac arrest to determine if it
      would interfere with neurological assessment. DESIGN: Two groups of children were
      studied. Group 1 consisted of 28 patients who received atropine (0.03 +/- 0.003
      mg/kg) prior to endotracheal intubation. Group 2 consisted of 21 patients
      previously without evidence of brainstem disease who suffered a witnessed arrest
      and had prompt return of spontaneous circulation and received an atropine dose of
      0.03 +/- 0.01 mg/kg. RESULTS: In group 1, pupillary size averaged 4.02 +/- 0.78
      mm before and 4.75 mm +/- .84 mm after atropine (P less than .001). In group 2,
      the pupillary examination was conducted 30 minutes after return of spontaneous
      circulation. The pupillary diameter was 4.80 +/- 0.91 mm. All pupils were
      reactive to light in both groups. CONCLUSION: Atropine administration in
      conventional dose causes slight pupillary dilation but does not abolish pupillary
      light reactivity.

PMID- 1984730
TI  - Accidental firearm fatalities among New Mexico children.
AB  - STUDY HYPOTHESIS: Risk factors associated with unintentional gunshot fatalities
      among children include gender and race of the decedent, type of firearm used, and
      whether loaded guns are stored within the home. STUDY POPULATION: All New Mexico
      children 0 to 14 years old unintentionally killed by a firearm between 1984 and
      1988. METHODS: The New Mexico Office of the Medical Investigator master mortality
      file was reviewed retrospectively to identify all unintentional firearm
      fatalities occurring in New Mexico children during a five-year period. Medical
      investigator, autopsy, and police reports were analyzed to identify epidemiologic
      factors associated with these deaths. Chi-square and Fisher's exact tests were
      used to analyze the data. RESULTS: Twenty-five unintentional firearm fatalities
      were identified. These deaths occurred most frequently among children playing
      with loaded firearms found within the home. A disproportionate number involved
      handguns. CONCLUSIONS: The study results provide a basis for preventive
      strategies that limit accessibility or decrease lethality of loaded firearms
      within the home.

PMID- 1984731
TI  - Core temperature measurement in hypovolemic resuscitation.
AB  - STUDY OBJECTIVES: Accurate core temperature measurement in severely hypovolemic
      patients can be difficult to achieve. We used a dog model to determine both a
      convenient method of measuring core temperature and the relative accuracy of the
      multiple sites. DESIGN: Prospective laboratory (animal model) study. SETTING:
      Operating suites in the Animal Care Department. PARTICIPANTS: Eight adult,
      anesthetized greyhound dogs. INTERVENTIONS: Continuous temperature monitoring by
      thermistors placed in the brain, central vein, tympanic membrane, bladder,
      rectum, esophagus, and subcutaneous tissue. Hemorrhage to 65% initial
      intravascular volume and autologous transfusion of cooled blood, during which
      serial temperature measurements were recorded. MEASUREMENTS AND MAIN RESULTS: The
      readings were analyzed with Pearson's correlation coefficient. Brain temperature
      correlated very well with tympanic membrane temperature throughout the course (r
      = .869, P less than .0005). Rectum, bladder, and esophagus also correlated well
      with brain. Central venous temperature, however, correlated poorly with
      temperatures at all other sites, reflecting the marked swings in intravascular
      temperature caused by cold transfusion. These wide variations were damped at the
      other sites. The best correlation of central venous temperature was with brain
      and bladder, although tympanic membrane correlation was fair. CONCLUSIONS:
      Because intravascular hypothermia appears to be the source of the arrhythmias and
      hemostatic abnormalities often seen during the early resuscitation of hypovolemic
      patients, our results suggest bladder or tympanic membrane as the initial
      temperature site. After the initial resuscitation, end organ (eg, brain)
      temperature is the most important and is most accurately reflected by tympanic
      membrane temperature.

PMID- 1984732
TI  - Under-reporting of contaminated needlestick injuries in emergency health care
      workers.
AB  - STUDY HYPOTHESIS: There is considerable under-reporting of contaminated
      occupational needlestick and other sharp object injuries among emergency health
      care workers. POPULATION: A convenience sample of emergency physicians, emergency
      nurses, and emergency medical technicians (EMTs). METHODS: A survey instrument
      eliciting demographic and work-related factors was developed and administered;
      survey items included age, sex, occupation, years in occupation, number of
      procedures performed per week, number of contaminated needlestick (and other
      "sharps") injuries recalled, and number of these injuries formally reported
      during the previous five years. Nonsegmented visual analog scales were used to
      assess eight attitudes possibly associated with nonreporting. Analysis was by
      analysis of variance and multiple linear regression with stepwise variable
      election. RESULTS: Two hundred fifty-nine subjects recalled 643 contaminated
      exposures during the five-year study period, but only 228 (35%) were formally
      reported. One or more injuries occurred in 55% of EMTs compared with 72% of
      nurses and 80% of physicians (P less than .05). Physicians recalled a mean of 3.8
      contaminated exposures, whereas nurses recalled 2.8 and EMTs recalled only 1.8 (P
      less than .05). Physicians formally reported a mean of 0.26 exposures, whereas
      EMTs reported 0.85 and nurses reported 1.25 (P less than .05). Physicians
      formally reported only one eighth of their injuries compared with EMTs and
      nurses, who each reported two thirds of these events (P less than .05).
      Perception of risk, occupation, years in occupation, and concern about excessive
      paperwork were the most powerful predictors of low reporting rate (P less than
      .05). CONCLUSIONS: Work-related contaminated sharp object injuries are under
      reported by emergency health care workers, especially emergency physicians.

PMID- 1984733
TI  - Teaching the art of emergency medicine.
AB  - The devaluation of interpersonal skills in medical education and practice has
      contributed to the current breakdown of the patient-physician relationship. The
      proliferation of medical technologies and the rise of the medical-industrial
      complex require even greater competency in these skills. No guidelines exist for
      teaching and/or evaluating interpersonal skills within emergency medicine
      residency programs. A written survey sent to all directors of allopathic
      emergency medicine residencies revealed large differences among programs in terms
      of quantity of formal teaching and specific formats used. A literature review
      demonstrates the direct impact of interpersonal skills on patient care and
      suggests methods for measuring proficiency in these skills. Elements of a core
      curriculum are proposed.

PMID- 1984734
TI  - Code 9: a systematic approach for responding to medical emergencies occurring in
      and around a hospital.
AB  - Members of the public expect to receive efficient and appropriate medical care if
      they become acutely ill or injured while in or around a hospital. Our institution
      became aware of the need for an organized system to respond to such emergencies
      involving patients, visitors, local community residents, and hospital employees,
      both inside the hospital and on the grounds surrounding the building. A search of
      the literature did not provide information regarding such a response; a survey of
      surrounding hospitals revealed no such plan in effect in other institutions. We
      therefore designed a plan to be superimposed onto our existing system for
      responding to in-house cardiac and respiratory arrests ("codes"). The results
      after one and one-half years appear encouraging. We recommend the establishment
      of such an emergency response system in all health care institutions.

PMID- 1984735
TI  - Weapons possession by patients in a university emergency department.
AB  - STUDY OBJECTIVE: Violence in the emergency department, a not uncommon but complex
      phenomenon, may become more serious when patients possess weapons. Searches are
      used frequently to reduce this danger, though guidelines for searches are not
      well delineated. We examined our practices in order to formalize our guidelines.
      DESIGN: Retrospective chart review of patients found to be carrying weapons.
      SETTING: General, university-based emergency department in the Northwest.
      PARTICIPANTS: Of 39,000 patients seen during the 20-month study period, 500
      (1.3%) were searched. MEASURES AND MAIN RESULTS: Of all patients seen in the ED,
      92% were medical patients (153, 0.4% of whom were searched) and 8% were
      psychiatric patients (347, 11.1% of whom were searched). Weapons were found on 89
      patients (0.2% of all ED patients and 17.8% of all patients searched). Review
      showed that 24 (15.7%) medical and 60 (17.3%) psychiatric patients carried
      weapons. CONCLUSION: Although various factors contributed to a clear bias toward
      searching psychiatric patients, we believe that the rate of weapons possession
      did not support this bias.

PMID- 1984736
TI  - Emergency department approach to managing seizures in pregnancy.
AB  - Seizures in pregnancy pose risks for both the mother and the fetus and must be
      managed aggressively. Antiepileptic drugs have some teratogenic potential, but
      the risks are not as profound as reported in earlier literature. There is
      definitely less risk to the fetus from anticonvulsant exposure than from
      uncontrolled seizures. The evaluation of a pregnant woman with new-onset seizures
      is the same as for the nonpregnant patient, including head computed tomography
      with appropriate abdominal shielding. Status epilepticus management is based on
      IV benzodiazepines, phenytoin, or phenobarbital. Good fetal outcome is dependent
      on rapid seizure control. Management of eclampsia is controversial. There is
      little evidence that magnesium sulfate has anticonvulsant properties, and its use
      as such will probably decline steadily in the future. At present, it is
      reasonable to manage eclamptic seizures in the same way that status epilepticus
      is managed.

PMID- 1984737
TI  - Hangman's fracture in a 7-week-old infant.
AB  - The "hangman's fracture" in infancy and childhood is a bilateral avulsion of the
      pedicles or their synchondroses from the C-2 vertebral body, frequently with
      anterior dislocation of C-2 or C-3. We present the case of the youngest infant in
      the medical literature with a hangman's fracture and discuss anatomy, kinematics
      of injury, radiographic diagnosis, and treatment.

PMID- 1984738
TI  - Transmission of 'toxic strep' syndrome from an infected child to a firefighter
      during CPR.
AB  - Several cases of a toxic shocklike syndrome have been reported in the United
      States during the past five years in association with Streptococcus pyogenes
      infection. We report a case of a firefighter exposed during attempted CPR to the
      secretions of an S pyogenes-infected child. The firefighter developed an
      infection of the hand and subsequent febrile illness with hypotension,
      erythematous rash, renal failure, and hypocalcemia. Bacterial isolates of blood
      and cerebrospinal fluid from the deceased child were identical in type and
      exotoxin production with isolates grown from the hand wound of the firefighter.
      This is the first reported case of documented transmission of S pyogenes, causing
      a toxic shocklike syndrome in an emergency medical technician.

PMID- 1984739
TI  - Fatal Capnocytophaga canimorsus septicemia in a previously healthy woman.
AB  - A previously healthy 47-year-old woman presented to the emergency department with
      septic shock five days after a small dog bite on the dorsum of her hand.
      Capnocytophaga canimorsus was isolated from blood cultures. Despite intensive
      therapy, multiple organ failure developed, and the patient died 27 days after
      admission. Characteristics of Capnocytophaga (formerly CDC group Dysgonic
      Fermenter-2) infection are briefly discussed. This unusual outcome in a
      previously healthy patient and the need for careful management of dog bite
      wounds, even if initially very small, is emphasized.

PMID- 1984740
TI  - Central pulmonary embolism with normal ventilation/perfusion scan-diagnosis by
      nuclear pulmonary artery flow studies.
AB  - Pulmonary embolism, although uncommon in children, occurs in as many as 104 per
      100,000 pediatric patients. Undiagnosed and untreated pulmonary embolism has a
      high mortality rate; thus, a high index of clinical suspicion and reliable
      diagnostic modalities are necessary to ensure prompt and accurate diagnosis. We
      report the case of a patient with severe central pulmonary embolism with a normal
      ventilation-perfusion scan. The embolus was identified by a nuclear pulmonary
      flow study using dynamic imaging, which obviated the need for contrast pulmonary
      angiography. The traditional ventilation-perfusion scan may appear normal despite
      severe central pulmonary embolism. In this situation, early dynamic imaging is
      necessary to detect severe obstruction of the central pulmonary arteries. This
      approach may obviate the need for contrast pulmonary angiography in
      hemodynamically stable patients.

PMID- 1984741
TI  - Guidelines for combined training in emergency medicine and pediatrics leading to
      credentialing for American Board of Emergency Medicine and American Board of
      Pediatrics Examinations.

PMID- 1984742
TI  - Systemic lupus erythematosus after renal transplantation: patient and graft
      survival and disease activity. The Dutch Working Party on Systemic Lupus
      Erythematosus.
AB  - OBJECTIVE: To determine the outcome of renal transplantation in patients with
      systemic lupus erythematosus and end-stage renal failure and to compare disease
      activity after transplantation with disease activity before transplantation.
      DESIGN: Retrospective case finding using data for an 8-year period from the
      central registry for renal replacement therapy in The Netherlands. SETTING:
      Tertiary care hospitals with facilities for renal transplantation in the
      Netherlands. PATIENTS: Twenty-eight patients who fulfilled at least four of the
      American Rheumatology Association's criteria for the classification of systemic
      lupus erythematosus and who received a renal transplant. MEASUREMENTS: Actuarial
      survival rates for grafts and patients after transplantation, maximal nonrenal
      scores on the Systemic Lupus Erythematosus Disease Activity Index, and time
      adjusted disease exacerbation rates in all patients before and after
      transplantation. RESULTS: The actuarial graft survival rate at 1 year and 5 years
      was 68% (95% CI, 47% to 82%) and 54% (CI, 25% to 77%), respectively, whereas the
      actuarial patient survival rate was 87% (CI, 69% to 96%) at 1 and 5 years. High
      disease activity was not found to affect graft survival adversely before the
      start of renal replacement therapy or during dialysis. After transplantation,
      disease activity per patient and the overall incidence of disease exacerbations
      decreased. One case of recurrent lupus nephritis was seen. CONCLUSIONS: Patients
      with systemic lupus erythematosus and end-stage renal failure are excellent
      candidates for renal transplantation; disease activity after transplantation is
      sporadic and low, and the recurrence of lupus nephritis is rare.

PMID- 1984743
TI  - Omeprazole enhances the efficacy of pancreatin (pancrease) in cystic fibrosis.
AB  - We studied the effect of the addition of omeprazole (20 mg once a day) to
      treatment with pancreatin (Pancrease, Cilag, Herentals, Belgium), two or four
      capsules three times a day, on fecal fat excretion in a double-blind, crossover
      fashion in nine patients with cystic fibrosis having persistent steatorrhea while
      taking Pancrease, two capsules three times a day (mean fecal fat excretion,
      22.3%; range, 12% to 44%). Neither doubling of the dose of Pancrease nor addition
      of omeprazole to the lower dose of Pancrease significantly reduced fecal fat
      excretion (mean, 19.6% [range, 10% to 34%]; mean, 16.4% [range, 6% to 32%],
      respectively). However, addition of omeprazole to the higher dose of Pancrease
      (four capsules three times a day) significantly reduced fecal fat excretion when
      compared with the two doses of Pancrease alone (mean, 10.7%; range, 4% to 25%; P
      less than 0.01). We conclude that adjunct therapy with omeprazole reduces fecal
      fat excretion in cystic fibrosis provided that a high dose of Pancrease is
      supplied.

PMID- 1984744
TI  - Echocardiographic left ventricular mass and electrolyte intake predict arterial
      hypertension.
AB  - OBJECTIVE: To identify predictors of arterial hypertension. PATIENTS: One hundred
      thirty-two normotensive adults from a large employed population. METHODS:
      Echocardiography, standard blood tests, and 24-hour urine collection, at baseline
      and after an interval of 3 to 6 years (mean, 4.7 +/- 0.8 years). RESULTS: At
      follow-up, 15 subjects (11%; 7 men, 8 women) had a systolic blood pressure
      greater than 140 mm Hg or a diastolic blood pressure greater than 90 mm Hg or
      both (mean, 143 +/- 7 and 87 +/- 6 mm Hg, respectively). At baseline, subjects
      who developed hypertension had a greater left ventricular mass index than those
      who did not (92 +/- 25 compared with 77 +/- 19 g/m2 body surface area; P less
      than 0.005) and higher 24-hour urinary sodium/potassium excretion ratio (3.6 +/-
      1.7 compared with 2.6 +/- 1.4; P less than 0.04); there were no differences in
      race, initial age, systolic or diastolic blood pressure, coronary risk factors,
      or plasma renin activity. The likelihood of developing hypertension rose from 3%
      in the lowest quartile of sex-adjusted left ventricular mass index to 24% in the
      highest quartile (P less than 0.005); a parallel trend was less regular for
      quartiles of the sodium/potassium excretion ratio (P less than 0.04). In
      multivariate analyses, follow-up systolic pressures in all subjects and in the
      117 who remained normotensive were predicted by initial age, systolic blood
      pressure, black race, and sex-adjusted left ventricular mass index; final
      diastolic blood pressure was predicted by its initial value, plasma triglyceride
      levels, urinary sodium/potassium ratio, low renin activity, black race, and
      plasma glucose level. CONCLUSIONS: Echocardiographic left ventricular mass in
      normotensive adults is directly related to the risk for developing subsequent
      hypertension. Left ventricular mass improves prediction of future systolic
      pressure, whereas diastolic pressure is more related to initial metabolic status.
      Black race is also an independent determinant of higher subsequent blood
      pressure.

PMID- 1984745
TI  - Barrett esophagus after chemotherapy with cyclophosphamide, methotrexate, and 5
      fluorouracil (CMF): an iatrogenic injury?

PMID- 1984746
TI  - Hypertension associated with endothelin-secreting malignant hemangioendothelioma.

PMID- 1984747
TI  - National Education Programs Working Group report on the management of patients
      with hypertension and high blood cholesterol.
AB  - Cardiovascular diseases are responsible for nearly one of every two deaths in the
      United States, and have been estimated to cost more than $127 billion annually.
      Epidemiologic data have shown that persons with fewer or lower levels of the risk
      factors for cardiovascular disease are less likely to have a cardiovascular
      event. In addition, the greater the level of any single risk factor, the greater
      is the chance of incurring disease. Moreover, a combination of risk factors
      creates a synergistic effect, further increasing risk. Conversely, reducing the
      number and level of risk factors prevents death and disability from
      cardiovascular diseases. This report addresses the management of patients with
      several cardiovascular risk factors, placing a special emphasis on hypertension
      and high blood cholesterol. Nonpharmacologic therapy, in the form of proper diet,
      exercise, and smoking cessation, is the foundation for management of both
      hypertension and high blood cholesterol. Clinicians should use these nondrug
      measures as definitive or adjunctive therapy. Pharmacologic agents can be very
      beneficial in managing the risks imposed by elevated levels of blood pressure or
      blood cholesterol. In selecting medications, it is important to weight their
      benefits, costs, and potential untoward effects. Clinicians must consider these
      issues in managing patients with several risk factors but should not avoid
      managing any risk factor or quickly dismiss any particular mode of therapy simply
      because of the potential for adverse effects.

PMID- 1984748
TI  - Certification and recertification: one approach to professional accountability.
AB  - Professional accountability requires a self-regulating profession to set and
      maintain credible, useful standards for its members. Voluntary certification and
      recertification--evaluation by peers--serves the responsibility of the profession
      to establish and enforce its own standards. The goal of certification by the
      American Board of Internal Medicine is to improve the quality of medical care by
      ensuring that the certified internist and subspecialist possess the knowledge,
      skills, and attitudes essential to the provision of excellent care. Without a
      true constituency and with a valid certification process, the Board provides a
      credential sought by nearly every graduate resident and acceptable both to the
      profession and patients. Recertification now presents the opportunity to foster
      continuing scholarship and self-improvement throughout the career of an
      internist.

PMID- 1984749
TI  - Barrett esophagus: a sequela of chemotherapy.

PMID- 1984750
TI  - Have you ever meta-analysis you didn't like?

PMID- 1984751
TI  - Emergency psychiatry: a critical educational omission.

PMID- 1984752
TI  - Treatment of hyponatremia.

PMID- 1984753
TI  - ACE inhibitors for scleroderma renal crisis.

PMID- 1984754
TI  - Erythrocytosis after zidovudine for AIDS.

PMID- 1984755
TI  - Splenic infarction after cocaine use.

PMID- 1984756
TI  - Tuberculosis and HIV infection in Kenya.

PMID- 1984757
TI  - HIV infection after needlesticks.

PMID- 1984758
TI  - Heterogeneity in the inheritance of alcoholism. A study of male and female twins.
AB  - Genetic influence on risk for alcoholism was examined in a US treatment sample of
      50 monozygotic (MZ) and 64 dizygotic (DZ) male and 31 MZ and 24 DZ female same
      sex twin pairs. For the DSM-III composite diagnosis of Alcohol Abuse and/or
      Dependence, statistically significant MZ/DZ differences in concordance were found
      with male, but not female, twins. For specific diagnoses, MZ/DZ differences were
      found in male subjects for both Alcohol Abuse and Alcohol Dependence, while MZ/DZ
      differences in female subjects were found only for Alcohol Dependence. The male
      MZ/DZ concordance difference for composite diagnosis but not for Alcohol
      Dependence could be accounted for statistically by differences in age of onset
      between MZ and DZ probands. As with alcohol, differences in MZ/DZ concordance
      were found for DSM-III composite diagnoses of Other Substance Abuse and/or
      Dependence with male, but not female, twins. Using Epidemiological Catchment Area
      data to estimate the population base rates of both alcohol and other substance
      use disorders allowed for heritability analyses that showed genetic factors to
      have only a modest influence on overall risk in both sexes (heritability
      estimates of approximately 0.35 for male subjects and 0.24 for female subjects).
      However, evidence for heterogeneity in the pattern of inheritance was also found,
      suggesting forms of alcoholism that may be moderately to highly heritable.

PMID- 1984759
TI  - Suicide in twins.
AB  - Suicide appears to cluster in families, suggesting that genetic factors may play
      a role in this behavior. We studied 176 twin pairs in which one or both twins had
      committed suicide. Seven of the 62 monozygotic twin pairs were concordant for
      suicide compared with two of the 114 dizygotic twin pairs (11.3% vs 1.8%). The
      presence of psychiatric disorder in the twins and their families was examined in
      a subsample of 11 twin pairs, two of whom were concordant for suicide. Eleven of
      these 13 twin suicide victims had been treated for psychiatric disorder, as had
      eight of their nine surviving cotwins. In addition, twins in 10 pairs had other
      first- or second-degree relatives who had been treated for psychiatric disorder.
      Thus, these twin data suggest that genetic factors related to suicide may largely
      represent a genetic predisposition for the psychiatric disorders associated with
      suicide. However, they leave open the question of whether there may be an
      independent genetic component for suicide.

PMID- 1984760
TI  - Psychiatric disorders in relatives of probands with opiate addiction.
AB  - Previous research has documented high rates of major depression and antisocial
      personality in opiate addicts. This study was designed to investigate the
      relationship of dual diagnosis in opiate-addicted probands to family history of
      psychiatric disorders and substance use disorders in biological relatives.
      Psychiatric disorders and substance use disorders were evaluated using direct
      interview and family history in a sample of 877 first-degree relatives of 201
      opiate addicts and 360 relatives of 82 normal controls. Results indicate that (1)
      compared with relatives of normal subjects, opiate addicts' relatives had
      substantially higher rates of alcoholism, drug abuse, depression, and antisocial
      personality; (2) relatives of depressed opiate-addicted probands had elevated
      rates of major depression and anxiety disorders but not of other disorders,
      suggesting the validity of subtyping opiate addicts by the presence or absence of
      major depression; and (3) in contrast, relatives of antisocial opiate addicts had
      rates of disorders that were not significantly different from those of relatives
      of opiate addicts without antisocial personality. Implications of these findings
      for the classification and treatment of substance abuse are discussed.

PMID- 1984761
TI  - Psychiatric diagnoses of treatment-seeking cocaine abusers.
AB  - In a sample of 298 cocaine abusers seeking inpatient (n = 149) or outpatient (n =
      149) treatment, rates of psychiatric disorders were determined by means of the
      Schedule for Affective Disorders and Research Diagnostic Criteria. Overall, 55.7%
      met current and 73.5% met lifetime criteria for a psychiatric disorder other than
      a substance use disorder. In common with previous reports from clinical samples
      of cocaine abusers, these overall rates were largely accounted for by major
      depression, minor bipolar conditions (eg, hypomania, cyclothymic personality),
      anxiety disorders, antisocial personality, and history of childhood attention
      deficit disorder. Affective disorders and alcoholism usually followed the onset
      of drug abuse, while anxiety disorders, antisocial personality, and attention
      deficit disorder typically preceded drug abuse.

PMID- 1984762
TI  - Symptoms of tobacco withdrawal. A replication and extension.
AB  - Smokers (n = 315) who wished to quit were randomly assigned in a double-blind
      manner to groups using either nicotine or placebo gum. Self-reported and observed
      symptoms of tobacco withdrawal were collected before cessation and at follow-ups
      of 1 to 2 weeks, 1 month, and 6 months. Self-reported and/or observed anger,
      anxiety, craving, difficulty concentrating, hunger, impatience, and restlessness
      were the most prominent symptoms of tobacco withdrawal. These symptoms had
      returned to precessation levels by 1 month except increased weight, hunger, and
      craving continued for 6 months in many smokers. Nicotine gum decreased most
      symptoms, including craving and hunger but not weight. Abstinent smokers with
      more intense withdrawal were not more likely to relapse. Abstinent smokers who
      gained more weight were less likely to relapse.

PMID- 1984763
TI  - Valproate in the treatment of acute mania. A placebo-controlled study.
AB  - We conducted a placebo-controlled, double-blind study of valproate, a drug
      originally developed as an antiepileptic, in 36 patients with acute manic
      episodes who had previously failed to respond to or to tolerate lithium
      carbonate. Treatment duration was 7 to 21 days, with no other psychotropic
      medications permitted except lorazepam up to 4 mg/d during the first 10 days of
      treatment. Serum valproate concentrations were measured three times weekly; an
      unblinded investigator then adjusted dosage to produce serum concentrations
      between 50 and 100 mg/L. Valproate proved superior to placebo in alleviating
      manic symptoms. The 17 patients randomized to active drug demonstrated a median
      54% decrease in scores on the Young Mania Rating Scale as compared with a median
      5.0% decrease among the 19 patients receiving placebo. On the 100-point Global
      Assessment Scale of overall psychiatric functioning, patients receiving valproate
      improved by a median of 20 points as compared with a zero-point change with
      placebo. Significant differences also emerged on the Brief Psychiatric Rating
      Scale and in the number of supplemental doses of lorazepam required by the
      patients in each group. Substantial antimanic effects appeared within 1 to 4 days
      of achieving therapeutic serum valproate concentrations. Adverse effects were
      infrequent, with no adverse effect appearing significantly more frequently with
      valproate than with placebo. We conclude that valproate represents a useful new
      drug for the treatment of manic patients.

PMID- 1984764
TI  - Hyperactive boys almost grown up. V. Replication of psychiatric status.
AB  - We previously reported a prospective follow-up study of 101 young adult males
      whose conditions had been diagnosed as hyperactivity in childhood. Compared with
      controls, probands had significantly higher rates of attention-deficit,
      antisocial, and drug use disorders at follow-up (mean age, 18 years). The present
      study was an attempt to replicate these findings on an independent sample of 94
      hyperactive boys who were seen at the same clinic, compared with 78 normal
      controls. Assessments were made by clinicians who were blind to group membership.
      Information was obtained for 90% of the original cohort. As in the previous
      study, significantly more probands than controls were given ongoing diagnoses of
      attention-deficit disorder (43% vs 4%), antisocial disorders (32% vs 8%), and
      drug use disorders (10% vs 1%). Furthermore, the absolute rates of these
      disorders were comparable for corresponding groups across studies, and the
      adjusted odds ratios did not differ significantly. As previously, there was no
      increased risk for affective disorders in the grown hyperactive children. The
      present study provides a powerful replication of the nature of the young adult
      outcome of childhood hyperactivity.

PMID- 1984765
TI  - Crow's 'lateralization hypothesis' for schizophrenia.

PMID- 1984766
TI  - Systemic lupus erythematosus in a boy with chronic granulomatous disease: case
      report and review of the literature.
AB  - We describe a patient with X-linked chronic granulomatous disease (CGD) who
      developed systemic lupus erythematosus, which was characterized by
      photosensitivity, malar rash, glomerulonephritis, leukopenia, hypocomplementemia,
      antinuclear antibodies, and anti-double-stranded DNA antibodies, at age 3. The
      patient's mother is an asymptomatic carrier of CGD, and her other son (the
      patient's half-brother) also has CGD. Neither the mother nor the brother has
      clinical or serologic evidence of systemic lupus erythematosus. Previous cases of
      discoid lupus-like skin lesions have been reported both in carriers and in
      patients with CGD. Our patient represents the first reported case of an
      individual with convincing clinical, serologic, and pathologic evidence of
      systemic lupus erythematosus. The association between defective host defense
      mechanisms and autoimmune phenomena has been described previously in patients
      with Job's syndrome and in patients with B cell and T cell deficiency disorders,
      including the acquired immunodeficiency syndrome. The relationship between the
      known leukocyte defects in CGD and the pathogenesis of a lupus-like illness is
      unclear.

PMID- 1984767
TI  - Prosthetic joint infections. A role for prophylaxis.

PMID- 1984768
TI  - Comment on the article by Kerolus et al.

PMID- 1984769
TI  - Heart block in systemic lupus erythematosus complicated by pacemaker "exit
      block".

PMID- 1984770
TI  - Accelerated nodulosis during azathioprine therapy.

PMID- 1984771
TI  - Comment on the article by Felson et al.

PMID- 1984772
TI  - False-positive findings in the atlantoaxial facet joints using the open-mouth
      view of the odontoid.

PMID- 1984774
TI  - Trapeziometacarpal osteoarthrosis in a painting by Diego Velazquez.

PMID- 1984773
TI  - Clinical outcome in patients receiving nonsteroidal antiinflammatory drugs.

PMID- 1984775
TI  - Use of the pinch strength meter in tender point examination.

PMID- 1984776
TI  - Relationship of clinical features with psychological status in primary
      fibromyalgia.
AB  - Clinical features and psychological status determined by the Minnesota
      Multiphasic Personality Inventory (MMPI) in 103 patients with primary
      fibromyalgia syndrome (PFS) were analyzed by univariate and multivariate
      techniques to determine if clinical features were related to psychological status
      or were intrinsic to PFS per se. The central features of PFS, e.g., number of
      pain sites, number of tender points, fatigue, and poor sleep, were independent of
      psychological status. However, discriminant analysis identified 4 variables-
      patient-reported depression, anxiety, stress, and pain severity--which together
      predicted 3 MMPI subgroups with an accuracy of 55% (P less than 0.001); the only
      musculoskeletal feature--pain severity--alone provided an accuracy of only 34% (P
      greater than 0.05). These data suggest a new concept, that the central features
      of fibromyalgia are independent of the psychological status and are more likely
      related to the PFS itself. However, pain severity may be influenced by
      psychological factors.

PMID- 1984777
TI  - Chondrons from articular cartilage. III. Morphologic changes in the cellular
      microenvironment of chondrons isolated from osteoarthritic cartilage.
AB  - Chondrons were isolated from human and canine osteoarthritic cartilage using low
      speed homogenization techniques. Changes in chondron morphology were evaluated
      using differential interference-contrast microscopy, phase-contrast microscopy,
      and histochemical and ultrastructural methods. Chondrocyte viability was assessed
      using fluorescein diacetate staining, and chondron metabolism was investigated
      using autoradiography. The results suggest that initial changes in the collagen
      and proteoglycan distribution within the chondron are followed by chondrocyte
      proliferation to form clusters. These techniques offer the potential to study
      cell matrix interactions in degenerative osteoarthritis.

PMID- 1984778
TI  - Progression of osteoarthritis of the hand and metacarpal bone loss. A twenty-year
      followup of incident cases.
AB  - We examined the prospective relationship between metacarpal bone mass and
      osteoarthritis (OA) of the hand, using incidence data from the historical cohort
      in the Tecumseh Community Health Study (Tecumseh, MI). Women were examined for
      radiographic evidence of OA and for bone mass twice, 20-23 years apart (1962-1965
      and 1985; 683 subjects with an age range of 55-74 in 1985). Two measures of OA
      were evaluated: the highest score assigned to any of the 32 wrist/hand joints,
      and the sum of scores for all wrist/hand joints. After adjustment for age, women
      who were classified as having OA (by either measure of OA) in 1985 were more
      likely to have more cortical area at baseline, which indicates greater bone mass.
      Women who developed OA in the 23-year period were more likely to experience a
      significantly greater widening of the medullary cavity over time, an indicator of
      increased bone resorption. Women with increasing levels of OA involvement also
      had an increased likelihood of greater cortical area loss. We conclude that women
      who later developed OA were more likely to have higher baseline bone mass than
      women who did not develop OA, but these women also had a greater likelihood of
      bone loss over time.

PMID- 1984779
TI  - Restoration of the DNA binding activity of estrogen receptor in MRL-lpr/lpr mice
      by a polyamine biosynthesis inhibitor.
AB  - Diverse data link estrogen influences to both the frequency and severity of
      systemic lupus erythematosus in humans and to murine lupus. A fundamental
      mechanism of action of estrogen involves the interaction of the hormone with its
      receptor protein, which is then transformed into the DNA binding form. We
      measured the concentration of uterine estrogen receptor and its DNA binding in
      normal BALB/c mice, lupus-prone MRL-lpr/lpr mice, and MRL-lpr/lpr mice that had
      been treated with 1% difluoromethylornithine (DFMO). Uterine estrogen receptor
      levels in 20-week-old mice from the 3 groups were not significantly different. In
      contrast, DNA binding activity was significantly higher in BALB/c mice (mean +/-
      SD 775 +/- 100 fmoles/mg of DNA) than in untreated MRL-lpr/lpr mice (80 +/- 16
      fmoles/mg of DNA) (P less than 0.001). Treatment with 1% DFMO was associated with
      an increase in uterine estrogen receptor DNA binding (1,100 +/- 218 fmoles/mg of
      DNA) in MRL-lpr/lpr mice (P less than 0.001). Polyamine levels were 2-6-fold
      higher in the uterine tissues of untreated MRL-lpr/lpr mice compared with the
      BALB/c mice and were significantly reduced by DFMO treatment. Our results link
      uterine polyamine production to a dysfunction of the estrogen receptors in MRL
      lpr/lpr mice. Reduction of the polyamine level by the irreversible inhibition of
      ornithine decarboxylase with DFMO restores estrogen receptor function.

PMID- 1984780
TI  - Septic arthritis of the C1-C2 lateral facet joint and torticollis: pseudo
      Grisel's syndrome.
AB  - We present the case of a 76-year-old man who experienced the sudden development
      of fever, rightsided neck pain and stiffness, and torticollis. A soft tissue mass
      was noted on the right side of his neck, but his head was tilted to the left.
      Computed tomography scans (with reformatted sagittal and coronal images) of the
      patient's cervical spine revealed destructive changes of the right lateral masses
      of C1 and C2 and the clivus, and a well-delineated peridontoid soft tissue mass
      (confirmed by magnetic resonance imaging). After the second episode of right
      sided hemiparesis, he underwent transoral surgical exploration, with anterior
      decompression and odontoidectomy. Histologic examination of the surgical material
      revealed granulation tissue, fibrosis, and chronic inflammation, consistent with
      abscess formation with invasion and compression of the spinal cord and bone. This
      case suggests that nonreducible rotational head tilt to the side opposite the
      side of lateral mass collapse should raise the suspicion of a possible infection.

PMID- 1984781
TI  - Application of the polymerase chain reaction and immunofluorescence techniques to
      the detection of bacteria in Yersinia-triggered reactive arthritis.
AB  - Leukocytes in synovial fluid and peripheral blood samples from patients with
      Yersinia-triggered reactive arthritis were analyzed after DNA amplification using
      the polymerase chain reaction. The primers applied were specific for the
      virulence plasmid-coded 1crE genes of Yersinia enterocolitica O:3 and Yersinia
      pseudotuberculosis III. No Yersinia DNA was observed within the synovial fluid
      cells or peripheral blood cells by polymerase chain reaction techniques. However,
      Yersinia antigens were detected in the synovial fluid cells by immunofluorescence
      techniques. These results suggest that only parts of the causative agents, not
      the entire microbe, can enter the joint and initiate the inflammation that leads
      to a reactive arthritis.

PMID- 1984782
TI  - Complete heart block and severe aortic incompetence in relapsing polychondritis:
      clinicopathologic findings.
AB  - We describe a patient with relapsing polychondritis who developed fatal cardiac
      involvement comprising complete heart block, acute aortic incompetence, and
      cardiovascular collapse. Pathologic studies showed fibrosis of the cardiac
      conducting system and necrotizing inflammation of the aortic valve, features not
      previously described in relapsing polychondritis, as well as evidence of coronary
      artery vasculitis.

PMID- 1984783
TI  - Stimulation by epidermal growth factor of inositol phosphate production in plasma
      membranes from A431 cells.
AB  - Plasma membranes were isolated from A431 cells previously labelled with myo
      [3H]inositol during exponential growth, using a rapid procedure on Percoll
      gradients. They displayed a significant phospholipase (PLC) activity against
      phosphoinositides, which was stimulated by guanosine 5'-O-(3-thiotriphosphate)
      (GTP gamma S), epidermal growth factor (EGF) and fetal calf serum (FCS) (24%, 11%
      and 97% over controls, respectively). The effect of EGF was not significantly
      increased by GTP gamma S. Upon addition of cytosol, EGF promoted an almost 100%
      stimulation of inositol 1,4,5-trisphosphate and inositol bisphosphate generation,
      which displayed an absolute requirement for GTP gamma S. This dose-dependent
      effect of cytosol was linear until 60 micrograms/ml of cytosolic protein and
      decreased afterwards; it was abolished by heat treatment and trypsin hydrolysis,
      and it was not reproduced by an identical amount of bovine serum albumin. The
      same biphasic stimulation was observed with phosphotyrosyl proteins
      immunopurified from cytosol of A431 cells previously stimulated by EGF. Since
      phosphotyrosyl proteins displayed PLC activity, our data suggest that soluble
      protein substrates of EGF receptor tyrosine kinase, including PLC, could be
      involved in the regulation of phosphoinositide hydrolysis in response to EGF.
      Using phosphatidyl[3H]inositol 4,5-bisphosphate (PIP2) dispersed with unlabelled
      phosphatidylethanolamine and phosphatidylserine as an exogenous substrate, no
      stimulation of PLC activity by EGF could be detected, either with membranes or
      with membranes plus cytosol. It is concluded that EGF might stimulate hydrolysis
      of phosphoinositides by PLC through complex interactions between plasma membrane
      and cytosolic factors which still remain to be identified.

PMID- 1984784
TI  - The interaction between chronic ethanol consumption and oxygen tension in
      influencing the energy state of rat liver.
AB  - Hepatocytes were isolated from chow-fed and liquid-diet control rats, and animals
      fed ethanol chronically for 31 days. These preparations were analyzed for adenine
      nucleotide and inorganic phosphate concentrations after being maintained under
      various conditions of oxygenation and nutrient availability. Hepatocytes from
      ethanol-fed animals resuspended at high cell density (oxygen tensions near zero)
      demonstrated a greater depression in cellular energy state as indicated by
      decreases in phosphorylation potential and energy charge. If, however, these
      hepatocytes were restored to high oxygen tension their energy state was
      equivalent to that observed with preparations from liquid-diet control animals.
      Moreover, their rate of oxygen consumption was equivalent to that of control
      hepatocytes. Analyses of livers from chow-fed, liquid diet control, and ethanol
      fed rats which were freeze-clamped while being perfused by the animal's blood
      revealed that there were no significant differences in the energy states of the
      hepatic tissue from these three animal groups. These results indicate that (1)
      the hepatic energy state in rats fed ethanol chronically is maintained under
      conditions of normal oxygen tension and (2) that hepatic tissue from these
      animals experiences a much more dramatic depression in energy state than tissue
      from control rats when subjected to oxygen deprivation.

PMID- 1984785
TI  - Damage to rat liver mitochondria promoted by delta-aminolevulinic acid-generated
      reactive oxygen species: connections with acute intermittent porphyria and lead
      poisoning.
AB  - delta-Aminolevulinic acid is a heme precursor accumulated in acute intermittent
      porphyria and lead-poisoning, which supposedly triggers the typical clinical
      expression associated with these diseases. Considering that: (i) erythrocyte anti
      oxidant enzymes are abnormally high in patients with both disorders and (ii)
      delta-aminolevulinic acid autoxidation generates reactive oxygen species, a
      possible contribution of reactive oxygen species in the pathophysiology of these
      disorders is explored here. Evidence is provided that delta-aminolevulinic acid
      (2-15 mM) induces damage to isolated rat liver mitochondria. Addition of delta
      aminolevulinic acid disrupts the mitochondrial membrane potential, promotes Ca2+
      release from the intramitochondrial matrix and releases the state-4 respiration,
      thus enhancing the permeability of the membrane to H+. The lesion was abolished
      by catalase, superoxide dismutase (both enzymes inhibit delta-aminolevulinic acid
      autoxidation) and ortho-phenanthroline, but not by mannitol; added H2O2 induces
      damage poorly. These results suggest the involvement of deleterious reactive
      oxygen species formed at particular mitochondrial sites from transition metal
      ions and delta-aminolevulinic acid-generated peroxide and/or superoxide species.
      These observations might be compatible with previous work showing hepatic
      mitochondrial damage in liver biopsy samples of acute intermittent porphyria
      patients.

PMID- 1984786
TI  - Ischemia decreases the content of the adenine nucleotide translocator in
      mitochondria of rat kidney.
AB  - The activity of the adenine nucleotide translocator is decreased at ischemia.
      Studies were undertaken to elucidate changes in the adenine nucleotide
      translocator by determining its content in mitochondria of ischemic rat kidney.
      After 60 min of ischemia, the content of the adenine nucleotide translocator
      amounted only to about 55%, of that measured in control mitochondria. At the same
      time, the flux control coefficient was increased. These changes paralled the well
      known effects of ischemia: the decrease in oxidative phosphorylation and in
      adenine nucleotides. It is supposed that the decrease in the adenine nucleotide
      translocatar content accounts, at least partially, for the ischemia-induced
      impairment of mitochondria.

PMID- 1984787
TI  - Effect of osmotic pressure on membrane energy-linked functions in Escherichia
      coli.
AB  - Osmotic upshock of E. coli cells in NaCl or sucrose medium resulted in a large
      decrease in the cytoplasmic volume and the inhibition of growth, of the electron
      transfer chain and of four different types of sugar transport system: the lactose
      proton symport, the glucose phosphotransferase system, the binding-protein
      dependent maltose transport system and the glycerol facilitator. In contrast to
      NaCl and sucrose, the permeant solute glycerol had no marked effect. These
      inhibitions could be partially relieved by glycine betaine. Despite these
      inhibitions, the internal pH, the protonmotive force and the ATP pool were
      maintained. It is concluded that inhibition of electron transfer and of sugar
      transport is the consequence of conformational changes caused by the deformation
      of the membrane. It is also concluded that the arrest of growth observed upon
      osmotic upshock is not due to energy limitations and that it cannot be explained
      by the inhibition of carbohydrate transport.

PMID- 1984789
TI  - Prevention of alloimmunization against platelets.

PMID- 1984788
TI  - Effects of pigment-protein interactions on the conformation of the primary
      electron acceptor in Rhodobacter capsulatus reaction centers.
AB  - Resonance Raman spectra are reported for RCs from Rb. capsulatus in which the
      L104 glutamic acid is replaced by glutamine. The skeletal modes of the primary
      electron acceptor, BPhL, in these RCs undergo temperature-dependent frequency
      shifts that are identical to those observed for BPhL in RCs from wild-type. This
      observation suggests that the strength of the hydrogen bond between the L104
      residue and the C9 keto group of BPhL is not a determinant of the temperature
      dependent conformation of this pigment.

PMID- 1984790
TI  - Identification of a platelet dense granule membrane protein that is deficient in
      a patient with the Hermansky-Pudlak syndrome.
AB  - Monoclonal antibodies were raised after injecting mice with isolated human dense
      granules. Several of these monoclonals were found to recognize a 40-Kd dense
      granule membrane protein. Western blot and immunofluorescent analysis confirmed
      the dense-granule specificity. After thrombin activation, the protein was found
      in patches on the external platelet membrane. By Western blot and slot blot
      analysis, the protein was found to be markedly deficient in a patient with the
      Hermansky-Pudlak syndrome. Studies of neutrophils and endothelial cells show the
      presence of immunologically related granule-membrane protein(s). Western blots
      using four anti-synaptophysin antibodies and three antibodies to the platelet 40
      Kd protein suggest that the protein may share some homology with, but is not
      identical to, the synaptosomal membrane protein synaptophysin.

PMID- 1984791
TI  - Studies on anti-von Willebrand factor (vWF) monoclonal antibody NMC-4, which
      inhibits both ristocetin- and botrocetin-induced vWF binding to platelet
      glycoprotein Ib.
AB  - Anti-von Willebrand factor (vWF) monoclonal antibody NMC-4 completely inhibited
      vWF binding to platelet glycoprotein (GP) lb induced by either ristocetin or
      botrocetin at an IgG concentration of approximately 10 micrograms/mL, and also
      blocked binding of asialo-vWF to GP lb. NMC-4 coupled beads isolated a 97-Kd
      fragment (Fr) from a whole tryptic digest of vWF. The N-terminal sequencing of
      the nonreduced 97-Kd Fr, in combination with amino acid analysis, showed it to be
      a homodimer of residues 449 through 728 of the constituent subunit. Present data,
      together with the results obtained from previous studies, confirm the existence
      of one or three possible inter-subunit disulfide bonds between cysteine residues
      459, 462, and 464. NMC-4 bound to reduced vWF Fr(s) more weakly than to
      nonreduced Fr(s), but it did not react with Fr III-T2 of vWF, a disulfide-linked
      twin heterodimer of residues 273 through 511 and 674 through 728 (Marti et al,
      Biochemistry 26:8099, 1987). Fr III-T2 completely inhibited ristocetin-induced
      vWF binding at a concentration of 100 mumol/L but had no effect on botrocetin
      induced binding. In addition, both the N- and C-terminal polypeptides, residues
      449 through 549 and 674 through 728, generated by subdigestion of the 52/48-Kd Fr
      (Fujimura et al, J Biol Chem 261:381, 1986), inhibited preferentially ristocetin
      induced vWF binding without affecting to botrocetin-induced vWF binding. These
      findings suggest that amino acid residues 512 through 673 of the vWF subunit are
      involved in botrocetin-induced vWF binding.

PMID- 1984792
TI  - Characterization of a novel self-associating Mr 40,000 platelet glycoprotein.
AB  - A novel platelet glycoprotein has been purified and characterized. This
      glycoprotein, designated Pltgp40, is an acidic sialylated 40,000-dalton protein
      that bears both O-linked and N-linked oligosaccharides. Treatment of Pltgp40 with
      neuraminidase resulted in a 5,000-dalton reduction in its Mr and a 1.5 Unit
      alkaline shift in the isoelectric point, indicating the presence of a large
      number of sialic acid residues. A similar size reduction and change in pl were
      observed after treatment of Pltgp40 with O-glycanase showing that sialic acids
      are present on O-linked oligosaccharides. Digestion of Pltgp40 with N-glycanase
      reduced the Mr to approximately 20,000 daltons but did not affect the isoelectric
      point, suggesting that Pltgp40 contains six to seven nonsialylated N-linked
      carbohydrate chains. High Mr proteins were observed in affinity purified Pltgp40
      and were identified as detergent-stable protein oligomers consisting of multiple
      40,000-dalton monomers. Immunodepletion and direct binding studies indicated that
      Pltgp40 was not equivalent to Ig Fc receptor type II, another 40,000-dalton
      glycoprotein expressed on platelets. However, Pltgp40 copurified with Fc receptor
      type II when platelet extracts were loaded onto human IgG affinity columns,
      raising the possibility that Pltgp40 may associate with Fc receptors or Fc
      receptor-lg complexes. Amino acid sequence analysis of the N-terminus of Pltgp40
      was performed and confirmed that Pltgp40 is a novel platelet glycoprotein.
      Epitopes on Pltgp40 appear to be widely expressed because monoclonal antibodies
      against Pltgp40 also reacted with a variety of myeloid, lymphoid, and epithelial
      cells. Pltgp40 was detected on activated but not resting platelets, indicating
      that Pltgp40 is a platelet activation marker.

PMID- 1984793
TI  - Expression of c-myb and B-myb, but not A-myb, correlates with proliferation in
      human hematopoietic cells.
AB  - The steady-state expression of three members of the myb family of genes, c-myb, B
      myb, and A-myb, was studied in four purified normal human hematopoietic cell
      types, ie, T and B lymphocytes, monocytes, and granulocytes. The c-myb proto
      oncogene is low to undetectable in resting T and B lymphocytes and shows a
      biphasic induction in both cell types after mitogenic stimulation, with a first
      peak at 3 hours and a second and stronger induction at 44 to 72 hours. Study of
      the B-myb gene showed that this gene is low to undetectable in resting T or B
      cells and is strongly induced after mitogenic stimulation with a peak between 44
      and 72 hours in both cell types. Finally, the A-myb gene shows a pattern of
      expression in lymphocytes different from that of c-myb and B-myb. It is expressed
      in resting T lymphocytes and its levels gradually decrease after mitogenic
      stimulation to become undetectable at 48 hours. It is also expressed in a
      subpopulation of large B lymphocytes but not in in vitro activated B cells.
      Neither of the three members of the myb family of genes was expressed in
      monocytes and granulocytes, even after functional activation of these cells.
      Taken together, these data bring further evidence for the role of c-myb in
      cellular proliferation and on the basis of the kinetics of its induction relative
      to thymidine uptake, we hypothesize that it may have a role during G1 progression
      in addition to that already documented for entry into S phase. Furthermore, our
      studies indicate that another member of the myb family of genes, B-myb, may also
      be involved in cellular proliferation, because its expression correlates with the
      induction of mitogenesis.

PMID- 1984794
TI  - Toxicity and efficacy of anti-T-cell ricin toxin A chain immunotoxins in a murine
      model of established graft-versus-host disease induced across the major
      histocompatibility barrier.
AB  - Graft-versus-host disease (GVHD) was induced across the murine major
      histocompatibility complex by injecting C57BL/6 (H-2b) bone marrow and
      splenocytes into lethally irradiated B10.BR (H-2k) murine recipients. An
      immunotoxin (IT) composed of a pan T-cell monoclonal antibody called anti-Ly1
      (the murine homologue to human anti-CD5) was conjugated to ricin toxin A chain
      (anti-Ly1-RTA) and used to treat recipient mice. In vitro, IT was as active as
      free RTA, bound selectively, and inhibited T-cell proliferation even in the
      absence of potentiators. Mice administered anti-Ly1-RTA in vivo during ongoing
      GVHD, at a dose of 10 micrograms/d for 5 days, showed lower numbers of splenic
      Thy1.2+ T cells and significantly improved survival as compared with mice given
      phosphate-buffered saline (PBS) or irrelevant control RTA IT. Protection was
      transient because GVHD and weight loss occurred when injections ceased. Survival
      could not be enhanced by crosslinking RTA30, a low oligosaccharide-containing
      fraction of purified RTA. Treatment with anti-Ly1-RTA caused a significant
      elevation in neutrophils, and higher doses were associated with mild
      hepatotoxicity. In contrast, infusion of identical doses and schedules of another
      pan T-cell immunotoxin, anti-Thy1.2-RTA, caused a significant decrease in
      lymphocytes, but not neutrophils; a precipitous increase in weight; a decrease in
      total plasma protein (TPP); and an increase in pleural and peritoneal effusions
      reminiscent of vascular leak syndrome (VLS). Although the toxic effects of anti
      Thy1.2-RTA were too severe to show a survival advantage in a GVHD model,
      histopathologic studies showed a definite anti-GVHD effect. The most significant
      decline in GVHD as compared with the PBS-treated controls was observed in skin,
      and to a lesser extent, in liver and lung. To investigate the cause of IT
      toxicity, anti-Thy1.2-RTA was administered intraperitoneally to lethally
      irradiated B10.BR (H-2k) recipients of syngeneic bone marrow. These recipients
      showed the same weight gain, hypoproteinuria, and VLS observed in the GVHD model.
      Death occurred at higher anti-Thy1.2-RTA doses (30 or 50 micrograms/daily
      injections administered days 8 through 12 posttransplant). Anti-Thy1.2-RTA had a
      negligible effect on renal function, but histologic studies showed patchy dropout
      of the renal tubules. Treatment resulted in pulmonary vascular congestion, but
      there was no pathologic evidence of liver, brain, or colon toxicity. Weight gain
      was enhanced by irradiation because nonirradiated normal mice did not undergo
      such a precipitous weight increase.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1984795
TI  - Allogeneic marrow transplantation in patients positive for hepatitis B surface
      antigen.
AB  - Twenty patients who were positive for hepatitis B surface antigen (HBsAg)
      underwent allogeneic marrow transplant for malignancy or other underlying
      hematologic disease between 1975 and 1986. After transplant, one patient had
      serologic evidence of hepatitis B virus (HBV) reactivation whereas three patients
      had evidence of an immune response to HBV. Among four patients with serologic
      follow-up of 1 year or more, three remained positive for HBsAg and one became
      HBsAg negative. Six patients (30%) developed clinical evidence of venocclusive
      disease and seven patients (35%) developed acute graft-versus-host disease
      involving the liver, but the incidence of these complications was similar to that
      expected among patients who are not carriers of HBsAg. Three patients died with
      hepatorenal failure, but all three had venocclusive disease and the contribution
      of HBV infection to liver failure was unclear. Available liver specimens obtained
      at autopsy (six patients) or biopsy (two patients) all showed either HBsAg (one
      specimen) or hepatitis B core antigen (four specimens) or both (three specimens)
      by immunoperoxidase staining. Although HBV reactivation leading to hepatic
      failure has been reported among allogeneic marrow transplant recipients as well
      as other immunocompromised patients, we did not observe an increase in the
      incidence of severe liver disease after transplant among these 20 patients
      positive for HBsAg at the time of transplant, and do not consider positivity for
      HBsAg to be a contraindication to allogeneic marrow transplantation.

PMID- 1984796
TI  - Observations on the effect of chimeric anti-CD4 monoclonal antibody in patients
      with mycosis fungoides.
AB  - Chimeric (murine/human) anti-CD4 monoclonal antibody was infused into seven
      patients with mycosis fungoides. Successive patients received doses of 10, 20,
      40, and 80 mg of antibody twice a week for 3 consecutive weeks. All patients had
      some clinical improvement, but responses were of relatively short duration. Serum
      levels of chimeric antibody varied as a function of dose. At the 80-mg dose
      level, antibody was readily observed in biopsied skin lesions. Although there was
      coating by antibody of most CD4 positive cells in the blood, there was no
      significant depletion of CD4 positive cells. Low-level antibody responses against
      the mouse Ig variable region and human Ig allotypic constant region determinants
      were observed in several patients, but none were of clinical significance. All
      but two patients made primary antibody and T-cell proliferative responses to a
      simultaneously administered foreign protein test antigen. However, there was
      marked suppression of the mixed lymphocyte reaction. We conclude that at the dose
      levels studied, a chimeric anti-CD4 monoclonal antibody (1) had some clinical
      efficacy against mycosis fungoides; (2) was well tolerated; (3) had a low level
      of immunogenicity; (4) had immediate immunosuppressive effects; and (5) did not
      induce tolerance to a co-injected antigen.

PMID- 1984798
TI  - Diagnosis of cobalamin deficiency.

PMID- 1984797
TI  - Use of leukocyte-depleted platelet concentrates for the prevention of
      refractoriness and primary HLA alloimmunization: a prospective, randomized trial.
AB  - Compared with conventional transfusion regimes a strong reduction in HLA
      alloimmunization and refractoriness to platelet transfusions is obtained when
      both red blood cell concentrates (RBCs) and platelet concentrates (PCs) are
      depleted of leukocytes by filtration. Because most of the leukocyte contamination
      is introduced by transfusion of RBCs, filtration of RBCs appears rational, but
      uncertainty exists regarding the degree of leukocyte-depletion of PCs needed for
      the prevention of HLA alloimmunization and refractoriness. We conducted a
      prospective trial and randomized patients with acute leukemia to receive
      leukocyte-depleted PCs prepared either by centrifugation (mean leukocyte count 35
      x 10(6)/PC of 6 U) or by filtration (mean leukocyte count less than 5 x 10(6)/PC
      of 6 U). Both groups received RBCs that were filtered after prior removal of the
      buffy coat. Clinical refractoriness occurred in 46% (12 of 26) of the evaluable
      patients that were transfused with centrifuged PCs and only in 11% (3 of 27) in
      the filtered group (P less than .005). De novo anti-HLA antibodies were detected
      in 42% (11 of 26) patients in the centrifuged group and only in 7% (2 of 27) of
      the patients receiving filtered PCs (P less than .004). In 8 of 11 alloimmunized
      patients in the centrifuged group antibodies were detected in the first 4 weeks
      of transfusion therapy while none of the patients in the filtered group became
      immunized against HLA antigens during that period. We conclude that for the
      prevention of HLA alloimmunization and refractoriness to platelet transfusions
      from random donors, both RBCs and PCs have to be leukocyte-depleted by
      filtration.

PMID- 1984799
TI  - Effect of fish oil on platelet adhesiveness.

PMID- 1984800
TI  - High risk of severe bleeding in aged patients with chronic idiopathic
      thrombocytopenic purpura.
AB  - The purpose of this study was to estimate the incidence and to establish which
      factors were associated with an increased risk of hemorrhagic complications in an
      historic cohort of 117 consecutive and unselected patients with chronic
      idiopathic thrombocytopenic purpura (ITP). Sixty-eight patients (58%) underwent
      medical treatment and/or splenectomy and 33 (48% of treated) achieved a complete
      stable remission. At equivalent platelet count the incidence of major hemorrhagic
      complications was significantly higher in aged (greater than 60 years) than in
      younger (less than 40 years) patients (10.4% v 0.4%/pt-y, relative risk = 28.9, P
      less than .01). A previous hemorrhagic event was identified as another major risk
      factor for hemorrhage (relative risk = 27.5, P less than .0005), while
      hypertension and underlying disorders had no influence. We conclude that age more
      than 60 years and a previous history of bleeding are major risk factors for
      severe hemorrhages in adults with ITP.

PMID- 1984801
TI  - Multiple in vivo effects of interleukin-3 and interleukin-6 on murine
      megakaryocytopoiesis.
AB  - The in vivo effects of interleukin-3 (IL-3), interleukin-6 (IL-6), and a
      combination of IL-3 plus IL-6 on murine megakaryocytopoiesis and thrombopoiesis
      were examined. Human recombinant IL-6 was administered subcutaneously as 14 equal
      injections of 5,000 units each during a 102-hour period. Murine recombinant IL-3
      was given as 8 injections of 80,000 units each during the first 54 hours.
      Megakaryopoiesis and thrombopoiesis were evaluated 120 hours after initial
      administration of the cytokines. Platelet levels increased by 20% following IL-3
      alone, 35% following IL-6 alone and 61% after administration of both IL-3 and IL
      6. Platelet production, as measured by 75Se-selenomethionine incorporation,
      increased by approximately 120% in animals that had received IL-6 or IL-3 plus IL
      6. Megakaryocyte ploidy analysis by two-color flow cytometry showed a shift in
      the modal ploidy class from 16N to 32N and a significant increase in the
      frequency of 64N cells only in IL-6 treated animals. Both bone marrow and splenic
      megakaryocyte colony-forming cells were significantly increased following either
      IL-3 or IL-6. Bone marrow megakaryocyte size increased 18%, 43%, and 38%,
      respectively, after administration of IL-3, IL-6, or the combination of IL-3 plus
      IL-6. Leukocyte counts and hematocrits were unaffected by either cytokine.
      Additional groups of mice received the same injection schedule as above and the
      serial effects on peripheral blood cell levels were assessed for 30 days.
      Platelet levels, which had been elevated by IL-3 or IL-6, fell to control values
      within 4 days following the last injection. Animals given IL-6 or IL-3 plus IL-6
      were subsequently thrombocytopenic relative to controls on days 7 through 9
      following cessation of treatment. Temporary 'cycling' of platelet levels was
      observed for 3 weeks following treatment with IL-6 or the combination of IL-3
      plus IL-6. We conclude that IL-6 and to a lesser extent IL-3 stimulate platelet
      production in vivo and that their combined effects on platelet levels are
      approximately additive. Following discontinuation of IL-3 or IL-6, the effects
      are rapidly reversed, presumably by negative feedback mechanisms, resulting in a
      period of 'rebound thrombocytopenia' in mice that had received IL-6.

PMID- 1984802
TI  - Stimulation of megakaryocytopoiesis in mice by human recombinant interleukin-6.
AB  - The in vivo effects of purified human recombinant interleukin-6 (IL-6) on murine
      megakaryocytopoiesis were examined. IL-6 was administered subcutaneously to Swiss
      Webster mice, followed by evaluation of bone marrow megakaryocyte ploidy, size
      and frequency, and median platelet volume 24, 48, and 72 hours after the
      initiation of IL-6 administration. In addition, bone marrow megakaryocyte
      morphology was examined using electron microscopy at 72 hours. IL-6 (10,000 U per
      subcutaneous injection) was administered three times during the first 24 hours,
      three times during the second 24 hours, and twice during the last 24-hour period.
      IL-6 bioactivity (10 U/ng) was determined using the IL-6-dependent murine
      hybridoma cell line B9. Megakaryocyte ploidy distribution, measured by two-color
      flow cytometry, demonstrated a shift in the modal ploidy class from 16N to 32N
      and a significant increase in the relative frequency of 64N megakaryocytes 48 and
      72 hours (but not 24 hours) after initiation of IL-6 administration (cumulative
      doses of 60,000 and 80,000 U at 48 and 72 hours, respectively). In addition,
      ploidy levels were increased in animals that received a cumulative IL-6 dose of
      only 40,000 U (evaluated after 72 hours). The size of recognizable bone marrow
      megakaryocytes, determined by the cross-sectional areas of plastic embedded bone
      marrow megakaryocytes, was increased at the 48-hour (60,000 U IL-6) and 72-hour
      (80,000 U IL-6) time points. Megakaryocyte frequency, measured by flow cytometry,
      was unaffected at all time points and doses of IL-6. Median platelet volume,
      measured by electrical impedance, was not consistently altered by administration
      of IL-6. Electron microscopic examination of bone marrow megakaryocytes showed an
      increase in the proportion of megakaryocytes with a wide, peripheral, organelle
      deficient zone from 20% +/- 9% (SD) in control animals to 50% +/- 7% (SD) (P less
      than .02) in animals that received IL-6. No changes were observed in the
      distribution of the demarcation membranes. IL-6 is a potent stimulator of murine
      megakaryocytopoiesis, in vivo, and appears to act early in megakaryocyte
      differentiation.

PMID- 1984803
TI  - Developing relationships: arterial platelet adhesion, glycoprotein Ib, and
      leucine-rich glycoproteins.

PMID- 1984804
TI  - Human thymic epithelial cells produce interleukin-3.
AB  - Interleukin-3 (IL-3) is a hematopoietic growth factor suggested to be produced by
      activated T lymphocytes. Meanwhile, supernatants from human thymic stroma could
      promote the proliferation of myeloid stem cells. Thus, we investigated whether IL
      3 accounts for this activity. Therefore, human thymic epithelial cells (TEC),
      fibroblasts, and adherent cells were isolated, and their culture supernatants
      assayed for myeloid colony promotion. Only supernatants from thymic epithelial
      cells supported colony-forming unit growth in semisolid media. This effect
      decreased following anti-IL-3 monoclonal antibody addition to these cultures.
      Furthermore, in situ hybridization showed the presence of IL-3 mRNA in epithelial
      cells. Effect of TEC culture conditions on IL-3 production by these cells was
      also studied. Together, these data show that IL-3 production is not the exclusive
      property of human activated T lymphocytes.

PMID- 1984805
TI  - Identification of a cell-surface antigen associated with activated T lymphoblasts
      and activated platelets.
AB  - We have identified and biochemically characterized an antigen, 8A3, which is
      expressed on activated T lymphoblasts and activated platelets. Monoclonal
      antibodies to 8A3 were raised against the primitive lymphoid/myeloid cell line
      KG1a and additionally bound to the erythroleukemia-derived cell line HEL, whilst
      exhibiting little or no reactivity with a panel of other hematopoietic cell
      lines. The 8A3 antigen was expressed on poorly differentiated T-cell leukemias
      and on phytohemagglutinin-activated T-cells maintained in interleukin-2 (7,000
      sites/cell). This antigen, though not detected on resting platelets, was
      expressed on thrombin-activated platelets (2,000 sites/platelet). Antibodies to
      8A3 identified polypeptides of Mr 170,000 and 150,000 in lysates of surface
      iodinated KG1a cells, T lymphoblasts, and activated platelets under both reducing
      and nonreducing conditions. However, peptide mapping and susceptibily to
      glycosidases indicated that the 8A3 antigen was a monomeric glycoprotein of Mr
      170,000 which contained two N-linked endoglycosidase H-sensitive glycans, and
      that the Mr 150,000 structure was derived from it by proteolytic degradation. The
      8A3 antigen was not detectably phosphorylated in KG1a cells in vivo, nor did
      immune complexes containing it exhibit kinase activity in vitro. Structural and
      serologic characteristics of the 8A3 antigen indicate that it is different from
      other previously described leukocyte activation antigens including transferrin
      receptors, interleukin-2 receptors, members of the integrin family of adhesion
      molecules, or "restricted" members of the leukocyte-common antigen/CD45 cluster.
      Furthermore, the 8A3 antigen does not appear to be related to the other
      previously described activation-specific platelet molecule, GMP140/PADGEM. This
      antibody may be useful in monitoring T-cell activation status in some clinical
      situations and in characterizing clinically relevant activation-associated
      platelet membrane alterations.

PMID- 1984806
TI  - Cancer statistics, 1991.

PMID- 1984807
TI  - Women in medicine: practice patterns and attitudes.

PMID- 1984808
TI  - Tennis elbow and computers.

PMID- 1984810
TI  - Military MDs used to peace prepare for war.

PMID- 1984809
TI  - Funding medical aid to the Third World.

PMID- 1984811
TI  - The thalassemias and health care in Canada: a place for genetics in medicine.

PMID- 1984812
TI  - Rapid evolution of microcomputer use in a faculty of health sciences.
AB  - OBJECTIVE: To assist with educational planning we surveyed health sciences
      faculty members in 1989 to determine their use of microcomputers, desire for
      further instruction and perceptions on what microcomputer services should be
      provided for students. The 1989 results were compared with those of a similar
      survey performed in 1986. DESIGN: A self-completed, mailed questionnaire, with up
      to three reminders. SETTING: Faculty of Health Sciences, McMaster University,
      Hamilton, Ont. PARTICIPANTS: All full-time (FT) and part-time (PT) faculty
      members were sent the questionnaire; over 80% of the FT and 65% of the PT faculty
      members responded in 1986 and in 1989. RESULTS: The proportions of faculty
      members who used microcomputers increased significantly over the 3 years, from
      71% to 87% among FT members (p = 2.2 x 10(-8)) and from 48% to 69% among PT
      members (p = 4.9 x 10(-8)). There were significant increases in the use of many
      of the applications, especially database and filing uses (from 10% to 41% among
      FT members [p less than 1 x 10(-9)] and from 6% to 34% among PT members [p less
      than 1 x 10(-9)]) and on-line access to bibliographic databases (from 7% to 37%
      among FT members [p less than 1 x 10(-9)] and from 3% to 18% among PT members [p
      less than 1 x 10(-9)]. These changes occurred mainly through individual
      initiative and voluntary continuing education. CONCLUSIONS: The extraordinary
      rate of adoption of microcomputers attests to their perceived usefulness.
      Curriculum planners need to consider how the success of microcomputer
      applications can be evaluated objectively and how successful applications can be
      integrated into educational programs.

PMID- 1984813
TI  - Effect of tetrahydroaminoacridine on cognition, function and behaviour in
      Alzheimer's disease.
AB  - OBJECTIVE: To determine the efficacy of tetrahydroaminoacridine (THA) in
      Alzheimer's disease. DESIGN: Randomized, double-blind, multiple crossover trial
      with three treatment periods, each consisting of 3 weeks of active drug therapy
      and 3 weeks of placebo administration. SETTING: Referral-based geriatric practice
      in a community hospital. PATIENTS: Thirty-four patients with moderate to severe
      Alzheimer's disease. Subjects were included if they had stage 3 to 6 disease (as
      determined by the Reisberg scale) and had not been taking psychotropic drugs for
      at least 1 month and if informed consent had been obtained from the patients and
      their next of kin. INTERVENTIONS: Fifty to 100 mg of THA daily and matched
      placebo. RESULTS: Of the initial 34 patients 14 experienced liver toxicity and 3
      gastrointestinal side effects during the study; however, all 22 who completed the
      study were able to tolerate at least the minimum dose. For the 22 patients there
      was no clinically or statistically significant effect of THA on cognition,
      functional status or behaviour. The results for individual patients showed no
      subgroup of THA-responsive patients. CONCLUSION: THA has no clinically important
      benefits in Alzheimer's disease and is associated with appreciable toxic effects.

PMID- 1984814
TI  - Mechanism of bronchodilator effect in chronic airflow limitation.
AB  - OBJECTIVE: To examine the mechanisms through which two bronchodilators
      (theophylline and salbutamol) influence dyspnea during daily activities. METHODS:
      Twenty-four patients with chronic airflow limitation participated in a multiple
      crossover, randomized, placebo-controlled trial. The effect of theophylline and
      salbutamol, alone or combined, on pulmonary function and dyspnea during daily
      activities was examined. Correlations of changes in forced expiratory volume in 1
      second (FEV1) and maximum expiratory pressures (MIPs) (independent variables) and
      changes in dyspnea score during daily activities (dependent variable) were also
      examined. RESULTS: The two drugs proved to be beneficial the effects in general
      were additive rather than synergistic. The drugs improved the FEV1; theophylline
      significantly improved the MIPs. The correlation between the changes in FEV1 and
      those in dyspnea score, after adjustment for the changes in MIPs, was 0.55 (p
      less than 0.001). The correlation between the changes in MIPs and those in
      dyspnea score, after adjustment for the changes in FEV1, was 0.39 (p less than
      0.001). CONCLUSIONS: Changes in airway calibre and in respiratory muscle strength
      play an independent and important role in dyspnea during daily activities in
      patients with chronic airflow limitation. Changes in airway calibre may be of
      greater importance.

PMID- 1984815
TI  - Medical home care services for the housebound elderly.
AB  - In our health jurisdiction the proportion of elderly people is more than double
      the national average, and there is a severe shortage of both home care services
      and long-term care beds. To help the many elderly housebound people without
      primary medical care we initiated a medical services home care program. The goals
      were patient identification, clinical assessment, medical and social
      stabilization, matching of the housebound patient with a nearby family physician
      willing and able to provide home care and provision of a backup service to the
      physician for consultation and help in arranging admission to hospital if
      necessary. In the program's first 2 years 105 patients were enrolled; the average
      age was 78.9 years. More than 50% were widowed, single, separated or divorced,
      over 25% lived alone, and more than 40% had no children living in the city. In
      almost one-third of the cases there had never been a primary care physician, and
      in another third the physician refused to do home visits. Before becoming
      housebound 15% had been seeing only specialists. Each patient had an average of
      3.2 active medical problems and was functionally quite dependent. Thirty-five of
      the patients were surveyed after 1 year: 24 (69%) were still at home, and only 1
      (3%) was in a long-term care institution; 83% were satisfied with the care
      provided, and 79% felt secure that their health needs were being met. One-third
      of the patients or their families said that it was not easy to reach the
      physician when necessary. We recommend that programs similar to ours be set up in
      health jurisdictions with a high proportion of elderly people. To recruit and
      retain cooperative physicians hospital geriatric services must be willing to
      provide educational, consultative and administrative support.

PMID- 1984816
TI  - Challenges of nutrition recommendations.

PMID- 1984817
TI  - The selling of ayurvedic medicine.

PMID- 1984819
TI  - Northern towns put out welcome mat for Ontario medical students.

PMID- 1984818
TI  - Why are there so many injuries? Why aren't we stopping them?

PMID- 1984820
TI  - Issues handled by CMA Council on Health Care multiplying.

PMID- 1984821
TI  - Eugenic abortion: an ethical critique.

PMID- 1984822
TI  - Etoposide. Current and future status.
AB  - Etoposide (VP-16-213) is an antineoplastic agent with demonstrated efficacy
      against a broad spectrum of human malignancies, including testicular, germ cell,
      lung, and other cancers. Etoposide can be synergistic with other agents. As part
      of combination chemotherapy, etoposide has become a so-called standard in
      therapies for testicular cancer and small cell lung cancer. Its activity in
      tumors such as lymphoma and leukemia, as well as solid tumors, identifies
      etoposide as a highly important chemotherapeutic agent. Cellular and animal
      models have shown that the cell kill and tumor response depend on both dose and
      time of exposure. Recent clinical studies again show that dose and schedule of
      etoposide can have important effects on clinical response to the drug. Further
      research should now continue: (1) on the use of etoposide as part of initial
      therapy in several cancers, and (2) in higher doses and prolonged schedules to
      optimize this agent's potential.

PMID- 1984823
TI  - Etoposide therapy for testicular cancer.
AB  - During the past two decades, dramatic strides have been made in the treatment of
      metastatic testicular cancer. In the early 1970s, cisplatin, vinblastine, and
      bleomycin (PVB) produced durable complete remissions (CR) in approximately 70% of
      treated patients. In the early 1980s, etoposide emerged as the only drug with
      single-agent activity in cisplatin-refractory patients. Based on preclinical data
      demonstrating synergy of cisplatin plus etoposide, the two-drug combination
      proved to be a useful salvage therapy, curing approximately 25% of such patients.
      Further evaluation of etoposide as part of initial therapy by the Southeastern
      Cancer Study Group (SECSG) compared PVB with bleomycin, etoposide, and cisplatin
      (BEP) in previously untreated patients with metastatic germ cell tumors. Not only
      did BEP have significantly less toxicity, it proved to be superior to PBV in
      patients with advanced disease. Varying the dose and schedule of etoposide also
      may provide patients with potentially useful avenues of treatment. High-dose
      etoposide plus carboplatin in drug-refractory patients has produced durable CR in
      a cohort of treated patients; it is currently being evaluated as part of initial
      salvage therapy. The schedule dependency of etoposide in small cell lung cancer
      led us to evaluate daily oral administration of etoposide in patients refractory
      to previous etoposide therapy; objective response rates of approximately 15% to
      25% were observed. In summary, etoposide remains an integral part of the
      treatment regimen for testis cancer. However, the incorporation of innovative
      dose and schedule combinations for etoposide may further improve its therapeutic
      index for this disease.

PMID- 1984824
TI  - New chemotherapies for ovarian cancer. Systemic and intraperitoneal
      podophyllotoxins.
AB  - The epipodophyllotoxin derivatives etoposide and teniposide have been evaluated
      intermittently for possible use in the treatment of ovarian cancer. Conflicting
      studies suggest that variables such as dose and prior treatment have a major
      influence on outcome. Response rates ranged from 0% to 40% in five series with
      teniposide, and from less than a 10% overall response rate to greater than a 10%
      complete response rate in nine studies with etoposide. One study documented
      activity with oral etoposide. However, because all patients had received various
      prior chemotherapies, firm conclusions regarding the activity of etoposide could
      not be drawn. These results, and the expectation of synergy with etoposide and
      cisplatin, led to several studies that combined etoposide with platin compounds
      by the systemic and intraperitoneal (IP) routes. Various studies have used
      intravenous drug combinations of these agents in both previously treated and
      untreated patients. One study, which used carboplatin instead of cisplatin,
      reported only seven failures among 26 previously untreated patients. Conversely,
      the prominent toxicities reported by another study were discouraging, and
      responses did not exceed what might be expected from cisplatin alone. Studies of
      analogous combinations administered IP are ongoing. A favorable experience, which
      was initially reported by the University of California (San Diego group), is
      being confirmed by other investigators. This has prompted the incorporation of
      etoposide into first-line strategies. The pharmacologic advantage of etoposide by
      the IP route (related to its high protein binding) may provide appropriate dose
      intensity against IP disease while sparing systemic toxicities. Finally, systemic
      dose intensity with autologous bone marrow support indicates some promise for
      etoposide in combination with high-dose alkylating drugs.

PMID- 1984825
TI  - Current strategies in the management of locoregional and metastatic gastric
      carcinoma.
AB  - Gastric carcinoma remains a significant cause of death worldwide. A patient's
      prognosis depends on the degree of gastric wall penetration, presence of lymph
      node metastases, and location of the primary site. Metastatic gastric carcinoma
      is currently incurable. However, chemotherapy continues to evolve at a rapid
      pace. Active agents include 5-fluorouracil (5-FU), doxorubicin, cisplatin,
      methotrexate, mitomycin, and etoposide. Combination etoposide, doxorubicin, and
      cisplatin (EAP) has been reported to result in encouragingly high response rates,
      including a 10% complete response rate in patients with metastatic gastric
      carcinoma. Trials are now under way to confirm these results. Similarly, another
      etoposide-based combination, etoposide, leucovorin, and 5-FU (ELF), has resulted
      in an equally good response rate but less toxicity than EAP. The 5-FU,
      doxorubicin, and methotrexate (FAMTX) regimen, previously reported to have an
      excellent response rate, is also being investigated further. For patients with
      locoregional carcinoma, curative resection rate is often unsatisfactorily low;
      however, curative resection is consistently associated with improved survival
      (between 23 and 26 months). In patients with potentially resectable carcinoma,
      two significant problems must be recognized: (1) a low rate of curative resection
      and (2) the development of widespread carcinoma despite curative resection.
      Despite many attempts, the postoperative strategies of adjuvant chemotherapy have
      been ineffective. New strategies must be investigated aggressively. Combination
      etoposide, 5-FU, and cisplatin (EFP) has been administered preoperatively and
      postoperatively to patients with resectable gastric carcinoma, resulting in an
      encouraging curative resection rate (greater than 70%) and manageable toxicity.
      Based on promising results reported with EAP in patients with unresectable
      locoregional carcinoma of the stomach, a trial of preoperative and postoperative
      EAP in potentially resectable carcinoma of the stomach is now under way.

PMID- 1984826
TI  - Etoposide in the management of metastatic breast cancer.
AB  - Etoposide, despite extensive use in other malignancies, has played a minor role
      in the treatment of patients with breast cancer. Single-agent trials in which
      etoposide is administered to heavily pretreated patients with metastatic breast
      cancer have demonstrated a low overall response rate (6.6% of 383 patients), with
      no convincing evidence for either schedule dependence or a relationship between
      dose intensity and response. The sole single-agent trial in previously untreated
      patients suggested that the drug has an approximately 15% response rate in
      untreated patients. Combination therapy trials in which etoposide has been
      combined with either cyclophosphamide, doxorubicin, or cisplatin have not yet
      convincingly demonstrated superiority over any of these drugs as single agents,
      although cisplatin plus etoposide appears to be superior to either agent alone.
      In vitro studies suggest that pretreating hormone-sensitive breast cancer cells
      with estradiol may increase their sensitivity to etoposide-induced DNA cleavage.
      This may represent a future direction in the use of etoposide in breast cancer.
      Currently, however, the use of etoposide in breast cancer should be considered
      investigational.

PMID- 1984827
TI  - The evolving role of etoposide in the management of lymphomas and Hodgkin's
      disease.
AB  - Etoposide, a derivative of epipodophyllotoxin, is one of the most important new
      drugs that was introduced into the management of the malignant lymphomas during
      the past decade. A growing number of specific protocols include this useful agent
      in the management of malignant lymphoma, both at the time of primary treatment
      and at relapse. The broad activity of etoposide across several histologic
      subtypes of malignant lymphoma and Hodgkin's disease indicates a potential that
      is only now being fully exploited. Used according to optimal doses and schedules,
      etoposide has single-agent activity that rivals earlier drugs such as the
      alkylating agents and doxorubicin. Functioning as a protein synthesis and
      topoisomerase II inhibitor, it offers the potential for non-cross-resistant
      cytotoxicity. After a brief comment on the single-agent activity of etoposide,
      this report will focus on the integration of etoposide into multiagent protocols
      used in the primary treatment of malignant lymphoma and Hodgkin's disease. The
      specific findings from protocols such as prednisone, methotrexate, doxorubicin,
      cyclophosphamide, etoposide-cytarabine, bleomycin, vincristine, and methotrexate
      (Pro-MACE-CytaBOM) (US National Cancer Institute [NCI]) and etoposide,
      doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (VACOP-B)
      (Vancouver) for the primary treatment of malignant lymphoma, and vinblastine,
      etoposide, cyclophosphamide, doxorubicin, bleomycin, vincristine, and prednisone
      (VECABOP) (Vancouver) for the treatment of previously untreated patients with
      advanced Hodgkin's disease will be discussed.

PMID- 1984828
TI  - Etoposide in acute leukemia. Past experience and future perspectives.
AB  - Etoposide as a single agent is active in relapsed and refractory acute
      myelogenous leukemia (AML), with complete responses (CR) rates of 10% to 25%. The
      drug has been safely combined with cytarabine, azacytidine, vinca alkaloids, and
      anthracyclines, inducing remission rates of 20% to 60% in patients with
      previously treated AML. The experience with etoposide in acute lymphoblastic
      leukemia is less extensive, but the drug seems to be active in combination with
      cytarabine or aclacinomycin. In addition, etoposide is combined with cytarabine
      and anthracyclines for the primary treatment of AML. The response rates thus
      achieved are comparable with those obtained with standard regimens. A Phase I/II
      trial was initiated to study the efficacy of the NOVE combination (mitoxantrone
      [10 mg/m2/d, days 1 to 5] plus etoposide [100 mg/m2/d for 3, 4, or 5 days] in
      patients with refractory AML. The results showed that extended duration of
      etoposide administration is associated with higher CR rates. Overall, a CR rate
      of 43% was achieved in 61 patients. A sequential regimen with IDAC
      (idarubicin/cytarabine) and NOVE was designed for primary treatment of adult
      patients with AML. Cycles of IDAC or NOVE are applied depending on response. The
      results of the pilot study with this strategy were encouraging with 18 of 20
      patients achieving CR. Further studies are under way to verify the efficacy of
      this strategy.

PMID- 1984829
TI  - Etoposide in leukemia.
AB  - Etoposide (VP16-213, NSC 141540) induces a complete response (CR) in 15% to 25%
      of previously treated patients with acute nonlymphocytic leukemia (ANLL) when
      used as a single agent. Etoposide has been used successfully in combination with
      cytarabine, daunorubicin, and amsacrine for salvage and consolidation therapies.
      Previously untreated ANLL patients 15 to 70 years of age were randomly assigned
      to cytarabine (100 mg/m2) on days 1 to 7 plus daunorubicin (50 mg/m2) on days 1
      to 3 (7-3) or to the same drugs plus etoposide (75 mg/m2) on days 1 to 7 (7-3-7).
      Patients achieving a CR received two consolidation courses (5-2, attenuated 7-3
      or 5-2-5). Among 264 eligible patients, there was a 56% CR rate with 7-3 therapy
      and a 59% CR rate with 7-3-7 therapy. Remission duration was significantly
      improved with 7-3-7 (median, 12 months with 7-3 and 18 months with 7-3-7; P =
      0.01), but survival was not. Subset analysis in patients younger than 55 years of
      age revealed prolonged remission (median, 12 months with 7-3 and 27 months with 7
      3-7; P = 0.01) and survival (median, 9 months with 7-3 and 17 months with 7-3-7;
      P = 0.04) with the 7-3-7 regimen. Hematologic toxicity was similar for both
      regimens during induction, but significantly more severe for 7-3-7 during
      consolidation therapy. Etoposide is active in ANLL and prolongs remission when
      used in induction therapy.

PMID- 1984830
TI  - High-dose etoposide and marrow transplantation.
AB  - Etoposide underwent conventional Phase I testing in the 1970s. The dose-limiting
      toxicity in these studies was mild myelosuppression; other toxicities were
      infrequent. If a greater degree of myelosuppression is accepted, higher than
      standard doses could be given. This approach takes advantage of the steep dose
      response relationship for most chemotherapeutic agents, including etoposide, as
      shown in early in vitro and clinical studies. Thus, etoposide was considered an
      ideal agent for further dose-escalation studies, given its wide range of clinical
      antitumor activity at standard doses, steep dose-response curve, mild bone marrow
      suppression, and few nonmyeloid side effects. The high-dose etoposide studies
      that followed used improved and more intensive hematologic supportive care,
      including, in some trials, autologous marrow transplantation. When etoposide was
      used as a single agent in these high-dose trials, mucositis, and, to a lesser
      degree, hepatic dysfunction were dose-limiting. The maximum tolerated dose (MTD)
      in this setting was 2.4 to 3.0 g/m2. Multi-agent Phase I trials with etoposide
      and cyclophosphamide, total body irradiation, carmustine, or carboplatin also
      resulted in dose-limiting mucosal toxicity, with liver and lung problems
      appearing more often than with high-dose etoposide alone. The toxicity and MTD
      can be influenced markedly by the schedule of administration. Etoposide as a
      continuous intravenous infusion can be given at doses of 4.2 g/m2 (with 200 mg/kg
      cyclophosphamide) with similar toxicity, but without marrow support. The
      antitumor results in the lymphomas set the stage for treatment of solid tumors,
      where treatment of patients with "sensitive" relapses had the best outcome.
      Lymphoma patients had an 80% response rate; overall, long-term (greater than 2
      years) disease-free survival was approximately 40%. Germ cell tumors were also
      responsive, and the same pattern of sensitive relapses and improvement in
      responding patients was seen (50% to 75% of patients greater than 1 year). In
      breast cancer and small cell lung cancer (SCLC), high-dose etoposide-containing
      regimens were used to intensify standard therapy. The results in these settings
      were not quite as good (breast cancer, 30% disease-free survival at 2 years;
      SCLC, 10% at 2 years).

PMID- 1984831
TI  - The pharmacology of intravenous and oral etoposide.
AB  - The epipodophyllotoxin derivative etoposide (VP-16) has been in widespread use
      both alone and in combination chemotherapy for the past decade. It has phase
      specific cytotoxicity that acts in the last S and G2 phases of the cell cycle.
      Although its mode of action is not certain, it appears to act by causing breaks
      in DNA by interaction with DNA-topoisomerase II or by the formation of free
      radicals. Most studies show biexponential decay after the intravenous (IV)
      administration of etoposide. Approximately 30% to 70% of administered etoposide
      is excreted, with approximately 45% present in the urine. Etoposide is available
      in oral and IV preparations. It is highly schedule-dependent, with once-daily
      doses (e.g., for 5 to 8 days every 21 days) giving results superior to
      intermittent administration. The bioavailability of oral etoposide is
      approximately 50%, but its absorption is not linear with increasing dose (e.g.,
      greater than 200 mg/d, bioavailability decreases). Factors influencing the
      bioavailability of oral etoposide include patient status, concurrent medications,
      hepatic and renal function, and nausea and vomiting. In numerous clinical trials,
      etoposide has demonstrated excellent activity against a range of tumors,
      including small cell lung cancer (SCLC), malignant lymphomas, gestational
      trophoblastic tumors, Ewing's and soft tissue sarcomas, and germ cell tumors,
      with more modest activity in other tumors (e.g., non-SCLC). Although few
      comparative studies have been carried out, available data suggest that oral
      etoposide administered daily during 5 to 8 days is similar to the IV preparation
      in range of activity. In a study of 53 elderly patients with SCLC treated with
      etoposide (200 mg/d for five times), there was a response rate of 79% and a
      median survival of 9.5 months. These results were similar to those achieved with
      more intensive IV regimens. Several studies of chronic oral etoposide (50 mg/m2/d
      for 21 times) have been reported recently. Responses were observed in SCLC and
      germ cell tumors among patients who had relapsed after standard etoposide
      containing regimens. These data suggest that etoposide may be a "new" drug when
      given in this schedule. The high response rates with oral etoposide suggest that
      oral administration may be substituted for IV administration. This substitution
      may allow for greater flexibility in chemotherapeutic administration, less
      hospitalization, and more acceptable toxicity.

PMID- 1984832
TI  - Chronic oral etoposide.
AB  - Etoposide is an important drug that has been recently incorporated with other
      agents in the curative treatment of patients with advanced neoplasms, including
      germ cell tumors, non-Hodgkin's lymphomas (NHL), and small cell lung cancer
      (SCLC). Etoposide demonstrates remarkable schedule dependency. A randomized
      comparison has shown an impressive survival difference for patients with
      extensive SCLC receiving a 5-day course versus those receiving a 1-day course.
      Because of these and previous clinical and laboratory data, etoposide is now
      given intravenously or orally in a 3-day to 5-day schedule. It is generally
      accepted that approximately 50% of the orally administered drug is absorbed. The
      authors have initiated several etoposide studies using an extended administration
      schedule, believing that a prolonged schedule may be superior to the standard 3
      day to 5-day schedule. This was initially tested in a Phase I study. Results
      showed that etoposide (50 mg/m2/d) given over 21 days was feasible and was
      associated with only moderate toxicity. Several Phase II studies have been
      completed or are nearing completion, including studies in patients with SCLC,
      NHL, germ cell tumors, soft tissue sarcoma, renal carcinoma, and ovarian
      carcinoma. Responses have been seen in all of these groups, particularly in
      patients with SCLC, lymphoma, and germ cell tumors. In these groups we saw
      responses in patients who were clearly resistant to etoposide plus cisplatin
      given in a standard schedule or in some patients who were resistant to high-dose
      etoposide with bone marrow transplantation. Investigators at Indiana University
      Medical Center who studied oral etoposide in a similar fashion in patients with
      advanced germ cell tumors and SCLC achieved results similar to those reported
      here. The authors have initiated a number of combination chemotherapy programs
      using the chronic oral form of etoposide. These include patients with SCLC, non
      small cell lung cancer, and elderly patients with high-grade and intermediate
      forms of NHL. In addition, chronic intravenous oral etoposide is being used in
      salvage approaches for patients with acute myelocytic leukemia and recurrent
      resistant intermediate-grade and high-grade NHL. Preliminary pharmacokinetic data
      suggest that a 50-mg/m2 oral dose is highly bioavailable (91% to 96%). Therefore,
      during a prolonged oral course at 50 mg/m2, many patients maintain a minimum
      plasma concentration of 1 microgram/ml. Further studies of multiple dose or
      continuous infusion etoposide to maintain a potentially critical plasma level are
      in progress. Etoposide administered in this way could represent a "new" drug
      because many of its features are different, and its activity spectrum may be
      broader.

PMID- 1984833
TI  - The role of etoposide in the treatment of poorly differentiated carcinoma of
      unknown primary site.
AB  - Patients with poorly differentiated carcinoma (PDC) or poorly differentiated
      adenocarcinoma (PDA) of unknown primary site comprise 25% to 35% of the patients
      with carcinoma of unknown primary site. Some of these patients have neoplasms
      that are highly responsive to combination chemotherapy, and a minority have
      potentially curable tumors. Between 1978 and 1982, 68 patients were treated with
      combination chemotherapy (most received cisplatin, vinblastine, and bleomycin
      [PVB] with or without doxorubicin). Thirty-eight patients (56%) responded to
      treatment, with 15 (22%) complete responder (CR) and 9 (13%) long-term, disease
      free survivors. Since that time, we have incorporated etoposide into the
      treatment of these patients because of its synergism with cisplatin and its great
      activity against several other neoplasms, including germ cell tumors. Seventeen
      patients with PDC of unknown primary site received salvage therapy with etoposide
      and cisplatin after failing PVB. Ten of these patients had partial responses
      (PR), with a median response duration of 5 months (range, 2 to 12 months). Thirty
      two previously untreated patients with PDC received etoposide and cisplatin
      combinations as initial treatment. Eighteen of 30 evaluable patients (60%)
      responded to therapy, and 11 patients (37%) had CR. Seven patients remain disease
      free 39 to 63 months after the completion of therapy. Etoposide is an active drug
      in the treatment of PDC of unknown primary site. Preliminary results indicate
      that initial treatment with etoposide and cisplatin combinations produces results
      equivalent to or superior to those achieved with PVB.

PMID- 1984834
TI  - Future directions for etoposide therapy.
AB  - Etoposide is an important chemotherapeutic agent in the treatment of selected
      patients with germ cell tumors, lymphomas, and small cell lung cancer (SCLC). Its
      optimal use is continuing to evolve. It is clear that schedule dependency is of
      critical importance. Recently, preliminary studies have suggested that a
      prolonged schedule of etoposide administration (21 days) may be more effective
      than the standard 3- to 5-day schedule. Results of several Phase II studies show
      chronic oral etoposide administration induces occasional responses in resistant
      tumors and higher-than-expected response rates in patients with germ cell tumors
      and SCLC. Preliminary data show nearly 90% etoposide absorption when given in a
      low-dose schedule (50 mg/m2/d) for 21 days. These observations indicate that
      etoposide may be a "new drug" when given in the chronic schedule. Further
      exploration of the schedule dependency of etoposide is indicated. Etoposide has
      recently been proven useful in selected patients with gastric, ovarian, and
      poorly differentiated carcinoma of unknown primary site. Several other drugs are
      either synergistic or additive and will be explored in combination chemotherapy.
      The possibility of adding topoisomerase I inhibitors and modulating etoposide's
      activity by inhibiting drug resistance is now within the realm of human testing.

PMID- 1984835
TI  - The clinical pharmacology of etoposide.
AB  - Etoposide, a semisynthetic derivative of podophyllotoxin, is increasingly used to
      treat cancer. Etoposide is a phase-specific, cytotoxic drug acting in the late S
      and early G2 phases of the cell cycle. It appears to cause breaks in DNA by
      either an interaction with DNA-topoisomerase II or the formation of free
      radicals. Most studies show a biexponential decay after the intravenous (IV)
      administration of etoposide. The peak plasma concentrations of drug and the area
      under the concentration versus time curve (AUC) are linearly related to the IV
      dose. Considerable interpatient variability of pharmacokinetic variables exists
      after IV etoposide. Various metabolites of etoposide have been identified, but
      their detection and quantitation are disputed. Approximately 30% to 70% of an
      etoposide dose is excreted. The bioavailability of oral etoposide is
      approximately 50%, but its absorption is not linear with increasing doses within
      the range in clinical use. Considerable interpatient and intrapatient variability
      exists in the pharmacokinetics of oral etoposide. There is no evidence of
      etoposide accumulation after multiple consecutive doses by either the IV or oral
      route. The exact roles of the liver and kidney in metabolism and excretion of
      etoposide are uncertain. Etoposide has been shown to be a highly schedule
      dependent drug in clinical studies. This, together with the phase-specific action
      of etoposide and its increasingly widespread use in treating cancer, makes the
      clinical pharmacology of this drug of great clinical importance.

PMID- 1984836
TI  - Leukemia and preleukemia in Fanconi anemia patients. A review of the literature
      and report of the International Fanconi Anemia Registry.
AB  - Fanconi anemia (FA) is an autosomal recessive disorder characterized clinically
      by a progressive pancytopenia, diverse congenital abnormalities, and increased
      predisposition to malignancy. Although a variable phenotype makes accurate
      diagnosis on the basis of clinical manifestations difficult in some patients, the
      unique sensitivity of FA cells to the clastogenic effect of DNA cross-linking
      agents such as diepoxybutane (DEB) can be used to facilitate the diagnosis. We
      review all cases of FA reported to have leukemia, preleukemia, or a bone marrow
      (BM) clonal chromosomal abnormality and include for the first time an analysis of
      these conditions observed in patients in the International Fanconi Anemia
      Registry (IFAR). The incidence of acute myelogenous leukemia (AML) in FA patients
      is more than 15,000 times that observed in children in the general population.
      Cytogenetic studies of FA-associated leukemias disclose a high frequency of
      monosomy 7 and duplications involving 1q. There were no occurrences of t(8;21),
      t(15;17), or abnormalities of 11q, which are associated with M2, M3, and M5
      leukemias, respectively, but not with preleukemia. Development of leukemia in FA
      patients was associated with an exceedingly poor prognosis, with a mean age of
      death of 15 years. We suggest that all FA patients may be considered preleukemic
      and that this disorder presents a model for study of the etiology of AML.

PMID- 1984837
TI  - Karyotypic abnormalities and immunoglobulin gene rearrangements in Hodgkin's
      disease.
AB  - Biopsy samples from seven patients with Hodgkin's disease (HD) were examined for
      cytogenetic abnormalities and rearrangement of the genes encoding the
      immunoglobulin chains and T-cell receptor chains. Three samples demonstrated
      clonal rearrangements of both IgH and IgL genes. No rearrangements of the TCR
      beta genes were detected in any of the samples. Karyotypic abnormalities were
      also found but only in the three cases where a clonal rearrangement of the
      immunoglobulin genes was shown. Two of these three cases had multiple karyotypic
      abnormalities, with the remaining patient being trisomic for chromosome 16 as the
      sole abnormality. These results are discussed and compared with previous reports
      in the literature concerning HD.

PMID- 1984838
TI  - ABO blood groups in hematologic malignancies.
AB  - This article examines the genetic predisposition of individuals to lymphoma and
      leukemia with regard to the ABO blood groups. Blood samples from 558 patients
      suffering from various forms of lymphoma and leukemia were collected and typed
      for ABO blood groups. The ABO blood group phenotype frequencies of lymphoma
      patients were similar to those in control samples. Among leukemia patients, a
      significant increase in the frequency of the A2 phenotype was found in chronic
      lymphocytic leukemia. Possible mechanisms underlying the predisposition of
      individuals with the A2 blood group to chronic lymphocytic leukemia suggested by
      these preliminary results are discussed.

PMID- 1984840
TI  - c-myc and K-ras-2 oncogenes in B-cell chronic lymphocytic leukemia with
      del(12)(p13).
AB  - Molecular and cytogenetic analyses were performed on chronic B-lymphocytic cell
      leukemia (CLL) from a 57-year-old male patient with del(12)(p13) anomaly. The
      deletion did not remove the K-ras-2 gene. However, c-myc gene amplification
      correlated with high-level expression, suggesting the involvement of this gene in
      the induction of neoplasia in this patient.

PMID- 1984839
TI  - Localization by in situ hybridization of three 3p probes with respect to the
      breakpoint in a t(3;8) in hereditary renal cell carcinoma.
AB  - Three 3p probes were localized by in situ hybridization on chromosomes from a
      carrier of a balanced t(3;8) associated with renal cell cancer. For one of the
      probes (pH3E4/D3S48), a previous localization in 3p21 was confirmed; for a second
      probe (pHF12-32/D3S2), a broader localization could be confined to 3p21. Both
      probes appeared to be located distal to the breakpoint in 3p. The third probe
      (pMS1-37/D3S3) was localized to 3p14, in accordance with a previous localization.
      This probe, however, hybridized very weakly or not at all to either of the
      translocation products, although it is known from Southern analysis that the D3S3
      sequence is present on one of them. We assume that this probe is located close to
      the breakpoint on 3p and that distortion of the higher-order chromosomal
      structure in this region is causing the failure of the in situ hybridization.

PMID- 1984841
TI  - Cytogenetic analysis of primitive neuroectodermal tumors. Absence of the t(11;22)
      in two of three cases and a review of the literature.
AB  - Cytogenetic analyses on direct and short-term cultures from three peripheral
      primitive neuroectodermal tumors (PNET) showed only one tumor with the
      t(11;22)(q24;q12), a translocation reported as characteristic of this tumor type.
      A second tumor contained rearrangements including apparent deletions of
      chromosomes 11 and 22 between bands 11q21 and 11qter and between bands 22q11.2
      and 22qter, respectively. A third tumor contained two normal copies of 11q but
      appeared to be monosomic for 22. We consider these findings in light of a survey
      of the PNET literature.

PMID- 1984843
TI  - Trisomy 10 in renal cell carcinoma.
AB  - We report four renal cell carcinomas, grade II, with trisomy 10 (+10) as the only
      karyotypic change. We propose that this cytogenetic anomaly may be associated
      with low-grade renal carcinoma, although more cases will have to be studied to
      support the hypothesis.

PMID- 1984842
TI  - Cytogenetic implication in adult T-cell leukemia. A hypothesis of leukemogenesis.
AB  - The close association between adult T-cell leukemia (ATL) and human T-cell
      leukemia virus type I (HTLV-I) has been established. Nevertheless, the mechanism
      of progression of ATL by HTLV-I infection is still uncertain, because the virus
      contains no typical oncogene and no significant expression of the viral RNA has
      been generally found. I propose a model of leukemogenic process in ATL based on
      our cytogenetic data and molecular results in the literature. It seems that the
      rearrangement of some proto-oncogene and alpha-chain gene of the T-cell antigen
      receptor (TCR-alpha) is necessary for the development to overt ATL. A deficiency
      in the rearrangement of proto-oncogene to TCR-alpha may result in only a minor
      proliferation of abnormal lymphocytes and remain in the preleukemic state of ATL
      or in the HTLV-I carrier state.

PMID- 1984844
TI  - 8;21 translocation with duplication of the der(21) in a patient with
      myelomonocytic leukemia.
AB  - An 8;21 translocation with duplication of the der(21) is described in a 72-year
      old man who presented with features of chronic myelomonocytic leukemia.
      Progression to acute myelomonocytic leukemia occurred within one month of
      diagnosis. The possible prognostic significance of the t(8;21) with duplicated
      der(21) in myelodysplasia is discussed.

PMID- 1984845
TI  - Cytogenetic findings in typical and atypical meningioma.
AB  - Comparative pathological and karyotypic findings of a typical and an atypical
      meningioma in two different patients are presented. The chromosomal abnormalities
      observed appeared unique for the histopathological subtype of the tumor.
      Cytogenetic analysis of atypical meningioma has not previously been reported.

PMID- 1984846
TI  - G-banding improvement for the MAC method.
AB  - Satisfactory identification of the neoplastic cell as well as an optimal G
      banding of its chromosomes are routinely obtained in our laboratory using a
      modification of the method described by Knuutila et al. Mitotic cells are first
      identified by either cytochemical or immunological staining. For G-banding, the
      preparations are then destained with methanol:acetic acid, treated with 2 x SSC
      at 65 degrees C and restained with Wright stain.

PMID- 1984847
TI  - Constitutive heterochromatin C-band polymorphism in prostatic cancer.
AB  - The size of the heterochromatin C-bands on chromosomes has been reported to be
      associated with some, but by no means all, human malignancies. No studies along
      these lines have been performed in prostatic cancer. We therefore investigated
      the size, incidence of inversions, and symmetry versus asymmetry of C-band
      heteromorphisms on chromosomes 1, 9, and 16 in peripheral blood lymphocytes from
      52 prostatic cancer patients and 183 healthy individuals. There were no
      differences in C-band heteromorphism on chromosomes 1, 9, and 16 between the
      patients and the controls. Neither were there any differences when patients with
      early-stage disease were compared with patients with more advanced cancer.
      Younger (aged less than 70 years) cancer patients had significantly higher
      frequencies of larger C-bands on chromosomes 1 (p less than 0.01) and 16 (p less
      than 0.001) than did patients aged more than 70 years at diagnosis. This could
      indicate a possible relationship between the amount of constitutive
      heterochromatin on chromosomes 1 and 16 and susceptibility to early development
      of prostatic cancer but could also result from the age differences between the
      two patient groups.

PMID- 1984848
TI  - Hypoplastic acute leukemia associated with inv(16)(p13q22).

PMID- 1984849
TI  - Acute nonlymphocytic leukemia with normal karyotype. Is its in vivo drug
      susceptibility age-dependent?
AB  - Nineteen patients with acute nonlymphocytic leukemia (ANLL) de novo who had no
      detectable chromosomal abnormalities received intensive remission induction
      chemotherapy. After the first chemotherapy cycle, ten of 14 (71%) patients aged
      60 years or less entered complete remission (CR) whereas none of five patients
      aged more than 65 years attained CR. On the other hand, leukemia showed a drug
      resistance in three (21%) of the former patients and in four (80%) of the latter
      patients. One patient in each group died during induction. Generally, older ANLL
      patients have an inferior CR rate after chemotherapy and a poor prognosis. This
      has been explained by the facts that the risk of induction death increases and
      that specific chromosomal abnormalities associated with poor prognosis are
      considerably more frequent in older patients. Our data may indicate, however,
      that in ANLL with normal karyotype older patients show a low initial response
      rate because of drug resistance.

PMID- 1984850
TI  - Reciprocal translocation involving 3q21 in an unusual myeloproliferative disorder
      with myelodysplastic features and prominent dysmegakaryopoiesis.
AB  - A case with an atypical myeloproliferative disorder (MPD) characterized by overt
      dysmyelopoiesis, mostly represented by abnormal thrombopoiesis and showing a
      t(3;18)(q21;q21), is described. The unusual hematological findings, which
      characterized a disease borderline between two distinct entities, namely MPD and
      myelodysplastic syndromes, are also discussed in relation to the cytogenetic
      abnormality affecting region 3q21 and possibly dictating the abnormal
      thrombopoiesis.

PMID- 1984852
TI  - Cytogenetic study in a bone marrow metastatic Merkel cell carcinoma.
AB  - We report an additional cytogenetic study of a metastatic Merkel cell carcinoma.
      Even though the cells analyzed were from a metastatic lesion, chromosomal
      abnormalities were not complex. Similarities between cytogenetic findings
      described in small-cell lung carcinoma and the present case are observed.
      However, further studies are needed to define the relationship between these two
      neuroendocrine small-cell malignancies.

PMID- 1984851
TI  - Cytogenetic evidence of involvement of an early progenitor myeloid cell in 4;11
      translocation-associated acute leukemia.
AB  - The t(4;11)(q21;q23)-associated acute leukemia may show both lymphoid and
      myelomonocytic features, which suggests a pluripotent progenitor stem cell as the
      hematopoietic cell involved in this neoplastic process. However, there is no
      cytogenetic evidence to support this contention. We present a case of acute
      myelomonocytic leukemia (M4, FAB subtype) with t(4;11)(q21;q23), which was also
      found in several hypertetraploid metaphases probably corresponding to
      megakaryocytes. This confirms the cellular origin in an early progenitor myeloid
      cell of this type of acute leukemia.

PMID- 1984853
TI  - Chromosome rearrangements in normal fibroblasts from xeroderma pigmentosum
      homozygotes and heterozygotes.
AB  - Chromosome analysis was carried out in cultured fibroblasts from unaffected skin
      of five unrelated xeroderma pigmentosum (XP) patients and nine family members.
      Structural chromosome changes were observed in cultures from all examined
      individuals. Furthermore, in one XPD patient and in one XPC patient and his
      parents, cytogenetically abnormal clones were detected. Some of these clones were
      present starting from the primary explant. This cytogenetic pattern is similar to
      that observed in an XPC patient previously studied by us. The analysis of
      breakpoint distribution from clonal and non-clonal chromosome rearrangements
      showed that some breakpoints were more frequent and common to different families
      or to different family members although definite evidence of preferential
      involvement of chromosome bands was not obtained. This investigation indicates
      that there is a consistent tendency toward chromosome instability in XP mutation
      carriers. The instability could be related to the multiple chromosome anomalies
      characterizing skin tumors in XP subjects.

PMID- 1984854
TI  - Decreased hydrodynamic resistance in the two-phase flow of blood through small
      vertical tubes at low flow rates.
AB  - The aggregation of red blood cells in blood flowing through small tubes at very
      low shear rates leads to the two-phase flow of an inner core of rouleaux
      surrounded by a cell-depleted peripheral layer. The formation of this layer is
      known to be accompanied by a decrease in hydrodynamic resistance to flow. To
      quantitate this effect, we measured the pressure gradient, flow rate, and the
      radius of the red blood cell core in suspensions flowing through tubes of 172
      microns radius at mean linear flow rates (U) from 50 to 0.15 tube diameters.sec
      1. Washed red blood cells were suspended in 1.5% buffered dextran 110 at
      hematocrits of 34-52%. Using syringe pumps, blood flowed from a stirred reservoir
      through a vertical 12-cm length of tube in either the upward or downward
      direction. The pressure drop was measured with transducers. Mean values in
      distributions in the core radius were obtained by analyzing cine films of flow
      taken through a microscope with flow in the upward direction, measuring the core
      radius at five equally spaced axial positions of the tube in each of 100 frames.
      At 34% and 46% hematocrit, the hydrodynamic resistance increased as U decreased
      from 50 sec-1, reaching a maximum at U-2 sec-1. It then decreased to a minimum at
      U less than 0.5 sec-1 as the red blood cell core formed in the tube, and the mean
      core radius/tube radius ratio decreased from 0.98 to 0.74 with marked axial
      fluctuations at the lower U. At higher hematocrits, both the increase and
      decrease in hydrodynamic resistance were greater. In a red blood cell albumin
      saline suspension, where there is no aggregation of red blood cells and no two
      phase flow, hydrodynamic resistance increases linearly with decreasing U. The
      experimental results were compared with the predictions of a two-phase steady
      flow model, assuming axisymmetric flow of a core surrounded by cell-free
      suspending medium. Two models were considered, one in which the core is solid,
      the other in which the rheological properties of the suspension in the core are
      given by the Quemada equation. The effects of sedimentation of the core resulting
      in a zero net flow pressure gradient were taken into account. Provided that an
      experimentally extrapolated value for the zero pressure gradient was used, the
      Quemada-fluid model gave good agreement with the experimentally observed core
      radius as a function of U and hematocrit.

PMID- 1984855
TI  - Role of basic fibroblast growth factor in vascular lesion formation.
AB  - In the present study we investigated whether basic fibroblast growth factor
      (bFGF) plays a role in the proliferative response of smooth muscle cells (SMCs)
      to denuding injury. Rat carotid smooth muscle was found to express the mRNA for
      bFGF, and bFGF protein was found to be present in rat aorta by immunoblot
      analysis. Systemically administered bFGF was a potent mitogen for vascular SMCs
      in arteries denuded with a balloon catheter, increasing replication from 11.5% in
      controls to 54.8%. Denudation with a device (filament loop), which causes only
      minimal damage to medial SMCs, showed a similar increase in replication (1.3%
      versus 43.3%) after bFGF infusion. In unmanipulated vessels, however, SMCs were
      unresponsive to infused bFGF. Infusion of a "mitotoxin" (bFGF conjugated to
      saporin) caused a greater than 50% decrease in the number of viable SMCs in the
      arterial wall after balloon injury. Prolonged administration of bFGF (12
      micrograms/day for 2 weeks) after balloon injury caused an approximately twofold
      increase in intimal thickening. These results show that bFGF, which is
      synthesized by the arterial wall, could be a potent mitogen for SMCs in vivo and
      suggest that any release of endogenous bFGF may be capable of stimulating SMC
      proliferation, which may subsequently lead to intimal lesion formation.

PMID- 1984856
TI  - Patterned growth of neonatal rat heart cells in culture. Morphological and
      electrophysiological characterization.
AB  - A culture method was developed that permits patterning of the growth of
      ventricular myocytes of neonatal rats. Regions were created on the culture
      substrate that either prevented (photoresist coat) or supported (glass surface)
      attachment of cells. In this way the geometry of interconnecting growth channels
      could be specified. Single-layered myocyte strands of variable length and with
      widths of as little as 65 micron (three to four cells wide) were obtained. The
      shape and orientation of the individual myocytes were a function of growth
      channel width: the narrower the channel, the more elongated the cells and the
      more likely was the long axis to be oriented along the channel axis. In channels
      with width of 100 micron or less, cells were aligned longitudinally and cross
      striated as in vivo. A high degree of morphological cell differentiation required
      the presence of contractile activity. Maximal diastolic potential (-71 mV),
      action potential amplitude (93 mV), and maximal upstroke velocity (140 V/sec) did
      not change with increasing culture age. Mean longitudinal conduction velocity was
      0.39 m/sec. No electrophysiological or morphological evidence of photoresist
      toxicity was seen, and the data indicate a high degree of cell differentiation in
      the patterned cell cultures. The method thus is suitable for the study of the
      relation between impulse propagation and structure at a cellular level in
      artificial networks of predefined shape.

PMID- 1984857
TI  - Nonadrenergic noncholinergic innervation. Anatomic distribution of calcitonin
      gene-related peptide-immunoreactive tissue in the dog heart.
AB  - Calcitonin gene-related peptide (CGRP) has inotropic and chronotropic effects in
      rat and guinea pig hearts. It also may mediate nonadrenergic noncholinergic
      regulation of canine cardiac electrophysiology. In this study,
      immunohistochemistry was used to determine the anatomic distribution of CGRP in
      mature dog heart and autonomic ganglia controlling cardiac function. The stellate
      ganglia had scattered CGRP-immunoreactive cells and nerve processes; intracardiac
      ganglia contained stained nerve processes but no CGRP-immunoreactive cells.
      Although the extramural coronary arteries were modestly innervated by varicose
      individual nerve processes, the great majority of CGRP-immunoreactive neural
      tissue in the heart existed adjacent to the sinoatrial node where varicose nerve
      processes coursed in numerous large nerve bundles. Each bundle contained only a
      few stained processes, however, indicating that CGRP-immunoreactive nerve
      processes were accompanying another type of autonomic tissue. Double staining and
      immunoultrastructure confirmed that the nerve bundles were heterogeneous. Similar
      nerve bundles were fewer in the left atrium, the region of the atrioventricular
      node, atrioventricular bundle, and the ventricles. In contrast to the
      distribution of sympathetic neural tissue, CGRP-immunoreactive nerve processes
      virtually were nonexistent among muscle fibers. We conclude that 1) CGRP
      immunoreactive neural tissue likely affects sympathetic and parasympathetic
      ganglia that control cardiac function, 2) the preponderance of this nonadrenergic
      noncholinergic tissue near regions of specialized muscle (especially the
      sinoatrial node) suggests an efferent function in the canine heart, and 3) the
      presence of varicosities along CGRP-immunoreactive nerve processes within
      heterogeneous nerve bundles may indicate that direct axo-axonal contact is the
      mechanism by which these nonadrenergic noncholinergic nerve processes modulated
      other autonomic neural tissue.

PMID- 1984858
TI  - Action potential propagation in a thick strand of cardiac muscle.
AB  - A theoretical model of action potential propagation in a thick strand of cardiac
      muscle is presented. The calculation takes into account the anisotropic and
      syncytial properties of the tissue, the presence of the interstitial space, the
      effect of the surrounding tissue bath, and the variation of the potential both
      along the strand length and across the strand cross section. The bidomain model
      is used to represent the electrical properties of the tissue, and the Ebihara
      Johnson model is used to represent the properties of the active sodium channels.
      The calculated wave front is curved, with the action potential at the surface of
      the strand leading that at the center. The rate of rise of the action potential
      and the time constant of the action potential foot vary with depth into the
      tissue. The velocity of the wave front is nearly independent of strand radius for
      radii greater than 0.5 mm. The conduction velocity decreases as the volume
      fraction of the interstitial space decreases. In the limit of tightly packed
      cells, an action potential propagates quickly over the surface of the strand; the
      bulk of the tissue is then excited by a slow inward wave front initiated on the
      surface. This model does not predict an increase in conduction velocity when
      cells are tightly packed, a hypothesis that has been proposed previously to
      explain the fast conduction velocity in Purkinje fibers of some species.

PMID- 1984859
TI  - Myocardial capillary permeability after regional ischemia and reperfusion in the
      in vivo canine heart. Effect of superoxide dismutase.
AB  - This study assesses the effect of the superoxide anion scavenger superoxide
      dismutase on myocardial capillary permeability-surface area (PS) products for
      small hydrophilic molecules after ischemia and reperfusion. Open-chest dogs
      underwent a 20-minute occlusion of the left anterior descending coronary artery
      followed by 1 hour of reperfusion. Myocardial plasma flow rate and capillary
      extraction of chromium 51-labeled EDTA or technetium 99m-labeled
      diethylenetriaminepentaacetic acid were measured by the single-injection, residue
      detection method before ischemia and 5 and 60 minutes after the start of
      reperfusion. In 13 dogs, no scavenger treatment was given (nonprotected control
      group), whereas eight dogs were treated systemically with 15,000 units/kg
      superoxide dismutase during 1 hour, starting 20 minutes before ischemia. In the
      control group, three dogs developed reperfusion ventricular fibrillation in
      contrast to none in the superoxide dismutase group. Before ischemia, plasma flow
      rate, myocardial capillary extraction fraction, and PS values were similar in the
      two groups. Five minutes after the start of reperfusion, plasma flow rate
      increased significantly (p less than 0.01) in both groups. In the control group,
      capillary extraction fraction increased by 12% (p = NS) in spite of the higher
      plasma flow; these increases in capillary extraction fraction and plasma flow
      induced a 69% increase in PS (p less than 0.01). In the superoxide dismutase
      treated group, capillary extraction fraction decreased by 32% (p less than 0.05)
      in accordance with the increased plasma flow rate, resulting in an unchanged PS
      (p = NS). Sixty minutes after reperfusion, plasma flow rate, capillary extraction
      fraction, and PS returned to preocclusion values in both groups (p = NS). The
      increased capillary extraction fraction and PS values seen in the control group
      suggest an increased capillary permeability after ischemia and reperfusion.
      Superoxide anions seem to participate, directly or indirectly, in this response.

PMID- 1984860
TI  - Oxidation of membrane cholesterol alters active and passive transsarcolemmal
      calcium movement.
AB  - Oxygen free radicals have the ability to oxidize cholesterol. However, nothing is
      known about the effects of cholesterol oxidation on ion transport in isolated
      myocardial membranes. The purpose of the present study was to investigate the
      effects of in situ oxidative modification of sarcolemmal cholesterol on Ca2+
      flux. Cholesterol oxidase was used to oxidatively modify membrane cholesterol.
      After incubation of cardiac sarcolemmal vesicles with cholesterol oxidase,
      cholest-4-en-3-one (cholestenone) was the predominant species of oxidated
      cholesterol produced. Cholesterol oxidase inhibited sarcolemmal Na(+)-Ca2+
      exchange in a concentration-dependent manner. Both the Vmax and Km of the
      reaction were altered after cholesterol oxidase treatment. Extensive treatment of
      the sarcolemmal membranes with cholesterol oxidase increased the passive
      permeability characteristics of the membrane. Passive Ca2+ efflux from the
      sarcolemmal vesicles was stimulated by increasing the concentration of
      cholesterol oxidase. ATP-dependent Ca2+ uptake was also inhibited after
      cholesterol oxidase treatment, but it was not as sensitive as the Na(+)-Ca2+
      exchange. Conversely, passive Ca2+ binding to sarcolemmal vesicles was strikingly
      stimulated by cholesterol oxidase treatment. The results demonstrate that
      oxidative modification of sarcolemmal membrane cholesterol can directly affect
      ionic interactions with the sarcolemmal vesicle and provide potentially important
      mechanistic information for the molecular basis of the effects of free radicals
      on ion flux and function in the heart.

PMID- 1984861
TI  - Adenine nucleotide changes in kidney, liver, and small intestine during different
      forms of ischemic injury.
AB  - The purpose of this study was to better characterize renal adenine nucleotide
      pool responses to different forms of shock, contrast the changes to those found
      in other intra-abdominal organs (the liver and small intestine), and assess
      whether these changes are closely mimicked by those produced by renal arterial
      occlusion, the usual method used to study ischemic acute renal failure. Rats were
      subjected to hemorrhagic shock, septic shock, or cardiopulmonary shock of varying
      severities and durations. The liver consistently had the greatest energy
      depletion, followed by the kidney, and then the small intestine. However, only
      the kidney developed clear morphological damage (S3 brush border sloughing).
      Kidney adenylate pools were better preserved during septic shock and
      cardiopulmonary shock than during hemorrhagic shock despite comparable blood
      pressures. Only profound hemorrhagic shock (35-40 mm Hg for 25 minutes) decreased
      total adenylate pools (ATP + ADP + AMP). However, the degree of renal catabolite
      (nucleosides plus purine base) accumulation did not correlate with the amount of
      renal total adenine nucleotide depletion, partially because circulating
      catabolites contributed to intrarenal catabolite pools. Purine base/uric acid
      ratios differed among shocked organs, consistent with different degrees of
      xanthine oxidase activity (small intestine greater than liver greater than
      kidney). Renal morphological damage decreased during the immediate (0-30 minutes)
      postshock period, and the extent of this improvement was not altered by xanthine
      oxidase inhibition (oxypurinol), suggesting that the immediate postshock period
      is not one of serious oxidative injury. Shock, in comparison with renal arterial
      occlusion, caused only modest ATP loss/catabolite accumulation, very low purine
      base/uric acid ratios, and no immediate-reperfusion (0-30 minutes) resynthesis of
      the total adenylate pool. Thus, ischemia-induced renal adenylate changes may
      differ considerably, depending on the nature of the ischemic event.

PMID- 1984862
TI  - Pericardial influences on right and left ventricular filling dynamics.
AB  - The influence of the pericardium on right and left ventricular filling was
      studied using two-dimensional and Doppler echocardiography in 14 open-chest dogs.
      Doppler echo parameters of filling included early (E) and late (A) velocities and
      their ratio (E/A) for the mitral and tricuspid valves. Right and left ventricular
      volumes were calculated from orthogonal two-dimensional echocardiographic images.
      Data were compared at three levels of left ventricular end-diastolic pressure (6
      +/- 2, 13 +/- 3, and 21 +/- 4 mm Hg) at matched heart rates before and after
      pericardiectomy. The instantaneous diastolic pressure gradient was measured in 12
      of the dogs. Pericardiectomy resulted in an increase in early mitral velocity,
      peak early diastolic pressure gradient, and E/A but not early mitral velocity
      normalized for end-diastolic volume. In contrast, for the tricuspid valve flow,
      pericardiectomy did not change E but caused a marked increase in A and a decrease
      in E/A. Right ventricular end-diastolic volumes at matched left ventricular end
      diastolic volumes were similar before and after the pericardium was removed.
      However, removal of the pericardium caused a significant decrease of the slope
      for the right (86.0 +/- 27.0 x 10(-4) versus 50.0 +/- 19.5 x 10(-4) mm Hg/ml, p
      less than 0.01), but not left, ventricular ln end-diastolic pressure-volume
      relation (21.2 +/- 9.2 x 10(-3) versus 21.4 +/- 5.3 x 10(-3) mm Hg/ml, p = NS),
      and a decrease of the pressure intercept for the left (3.0 +/- 2.0 versus 1.6 +/-
      0.9 mm Hg, p less than 0.05), but not right, ventricular ln end-diastolic
      pressure-volume relation (2.8 +/- 1.4 versus 1.4 +/- 0.8 mm Hg, p = NS). In
      conclusion, filling of the two ventricles is affected by the pericardium over a
      wide range of physiological ventricular volumes and pressures. At matched left
      ventricular end-diastolic volume, pericardiectomy causes a fundamental alteration
      in right, but not left, ventricular filling.

PMID- 1984863
TI  - L-arginine evokes both endothelium-dependent and -independent relaxations in L
      arginine-depleted aortas of the rat.
AB  - This study was designed to investigate the effects of L-arginine (the substrate
      for the formation of endothelium-derived nitric oxide) in vascular tissues. Rat
      aortic rings, with or without endothelium, were suspended in organ chambers for
      the measurement of isometric tension; they were contracted with phenylephrine
      (10(-6) M). After a short incubation period (0.5 hour) in physiological salt
      solution, L-arginine induced minor changes in both types of rings. In contrast,
      when the incubation time was increased (2, 4, 6, and 8 hours), L-arginine evoked
      concentration- and time-dependent relaxations in aortic rings both with and
      without endothelium. The relaxations were larger in rings with endothelium. The
      presence of L-arginine (10(-3) M) in the incubation medium inhibited subsequent
      relaxations evoked by the amino acid. The concentration-relaxation curves
      associated with acetylcholine in rings with endothelium and the curves associated
      with Sin-1, a spontaneous donor of nitric oxide, in rings with or without
      endothelium were slightly but significantly shifted to the right after a 6-hour
      incubation. Nitro-L-arginine (3 x 10(-5) M) and methylene blue (3 x 10(-7) M)
      attenuated the relaxations evoked by L-arginine in rings both with and without
      endothelium. Other basic amino acids (D-arginine, L-homoarginine, L-citrulline, L
      lysine, and L-ornithine; all tested at 10(-3) M) either had no effect or induced
      small relaxations and did not affect the response to L-arginine. These
      observations suggest that L-arginine specifically and stereoselectively relaxes
      aortic rings with and without endothelium, probably by restoring the endogenous
      pool of the amino acid, which is likely depleted by prolonged
      incubation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1984864
TI  - Effects of barium-induced cardiac contraction on large- and small-vessel
      intramyocardial blood volume.
AB  - We have measured the effects of barium-induced cardiac contraction on the
      intramyocardial blood volume content of all vessels and have independently
      measured the blood volume content of vessels with a diameter greater than 100
      microns in rat myocardium. Measurements of total intramyocardial blood volume
      were made by using [125I]albumin as a plasma marker and technetium-99m as a red
      blood cell marker. In one group of rats (n = 8), diastolic arrest was induced by
      an intravenous injection of KCl; in a second group (n = 8), systolic arrest was
      induced by an intravenous injection of BaCl2. In both groups, the hearts were
      frozen in situ immediately after heart arrest while aortic pressure was decaying
      from its former physiological level. The left ventricular free wall was sectioned
      transmurally in a cryomicrotome, and the blood volume within each tissue sample
      was calculated from its radioactivity. The volume of blood in vessels larger than
      100 microns was independently estimated from the exposed cross-sectional area of
      these vessels in photographs of the frozen tissue taken during tissue sectioning
      in the cryomicrotome. Total intramyocardial blood volume was found to decrease by
      about 42% from 8.6 +/- 1.3 ml/100 g (mean +/- SEM) in the KCl group to 5.0 +/-
      0.7 ml/100 g in the BaCl2 group (p less than 0.01). Total volume was greater in
      the epicardial than in the endocardial layers of both groups (p less than
      0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1984865
TI  - Ventricular pressure-area loop characteristics in the stage 16 to 24 chick
      embryo.
AB  - The accurate description of embryonic cardiovascular function requires the
      adaption of standard measurement techniques to the small scale of the developing
      heart. In the mature heart, the analysis of ventricular pressure and volume
      accurately defines function. Because in vivo measures of volume are not feasible
      in the embryonic heart, we tested the hypothesis that ventricular pressure-area
      loops accurately define ventricular function in the stage 16 to stage 24 white
      Leghorn chick embryo. We simultaneously measured ventricular pressure with a
      servo-null pressure system and recorded video images at 60 Hz. The pressure
      waveform was superimposed onto the video image in real time. Video fields were
      planimetered for epicardial ventricular cross-sectional area and ventricular
      pressure. Pressure and area data were smoothed using a fast Fourier transform
      filter and plotted. Data are reported as mean +/- SEM, n greater than or equal to
      4, and were tested by regression analysis and analysis of variance (p less than
      0.05). Heart rate increased from 90 +/- 7 beats/min at stage 16 to 130 +/- 13
      beats/min at stage 24. All pressure-area loops displayed diastolic filling,
      isometric contraction, ejection, and isometric relaxation, similar to pressure
      volume loops of the mature heart. Isometric contraction time increased from 42 +/
      5 to 62 +/- 4 msec (p less than 0.05), while isometric relaxation time was 124
      +/- 12 and 120 +/- 10 msec (p greater than 0.05) between stages 16 and 24,
      respectively. The maximum ratio of instantaneous ventricular pressure to area
      identified end systole better than peak ventricular pressure or minimum
      ventricular area. Thus, pressure-area relations define ventricular function in
      the embryonic chick heart.

PMID- 1984866
TI  - Mechanism of early ischemic contractile failure. Inexcitability, metabolite
      accumulation, or vascular collapse?
AB  - The basis of early ischemic contractile failure was investigated in perfused
      ferret hearts at 27 degrees C. Isovolumic left ventricular developed pressure
      fell by more than 50% within 30 seconds of the onset of total global ischemia and
      reached zero by 5 minutes. Monophasic action potential recordings revealed no
      decrease in excitability during this period. Phosphorus nuclear magnetic
      resonance spectra obtained at 30-second resolution showed no significant changes
      in inorganic phosphate or phosphocreatine during the first 30 seconds of
      ischemia. Intracellular pH (pHi) and ATP changed even more slowly; therefore,
      none of these metabolites could account for the rapid fall in force. To gauge the
      contribution of intravascular pressure, we compared ordinary aortic flow
      occlusion with tissue-level ischemia induced by massive coronary
      microembolization at the level of the precapillary arterioles. Functional
      depression developed significantly more slowly in the microembolized hearts,
      despite accumulation of inorganic phosphate and protons comparable with that in
      ordinary ischemia. After microembolization, the time course of functional
      depression reflected much more closely the concomitant inorganic phosphate and
      pHi changes. Thus, our results provide novel evidence supporting the importance
      of vascular collapse in the mechanism of early ischemic contractile failure.

PMID- 1984867
TI  - Effect of a pressor infusion of angiotensin II on sympathetic activity and heart
      rate in normal humans.
AB  - We tested the hypothesis that pressor infusions of angiotensin II (AII) could
      stimulate the sympathetic nervous system as reflected by norepinephrine (NE)
      spillover in humans. AII was infused at 5 ng/kg/min in six healthy volunteers,
      with vehicle and phenylephrine infusions as controls, on 3 separate days. Heart
      rate, mean arterial pressure, plasma NE, NE clearance, and NE spillover were
      assessed before and after 30-minute infusions of AII, vehicle, or phenylephrine
      in the supine position and then after 15 minutes of head-up and 15 minutes of
      head-down tilt. Both AII and phenylephrine raised mean arterial pressure (88 +/-
      9.6 to 103 +/- 14 mm Hg, p less than 0.001, and 91 +/- 7.6 to 104 +/- 9.2 mm Hg,
      p less than 0.001, respectively), whereas heart rate fell only with phenylephrine
      (60 +/- 6 to 51 +/- 6.3 beats/min, p less than 0.001). Neither plasma NE nor NE
      spillover was affected by either infusion, and NE clearance declined slightly
      with both. No changes occurred in any variable during vehicle infusions in the
      supine position. During upright tilt, NE spillover increases were attenuated by
      both AII and phenylephrine while NE clearance changes were slightly greater,
      leaving plasma NE increases similar on each day. During head-down tilt, NE and NE
      spillover declined comparably on each study day.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1984868
TI  - ATP-sensitive potassium channel modulation of the guinea pig ventricular action
      potential and contraction.
AB  - The role of ATP-sensitive potassium (KATP) channels in modulating the action
      potential and contraction of guinea pig ventricular myocytes was investigated.
      Under voltage clamp, the maximum whole-cell KATP channel conductance was
      estimated (195 +/- 10 nS, n = 6) by exposing the cells to complete metabolic
      blockade (2 mM cyanide in the presence of 10 mM 2-deoxy-glucose). In isolated
      inside-out membrane patches, the ATP dependence of KATP channel activity under
      relevant conditions was measured (half-maximal inhibition at 114 microM). Under
      current clamp (with intracellular ATP concentration = 5 mM), the effect of graded
      KATP channel activation on the action potential and the twitch was estimated by
      injection of a current (proportional to voltage) that simulated the KATP
      conductance. As this "conductance" was increased, the action potential was
      shortened, and contractile amplitude declined, as expected. From the results of
      these experiments, the quantitative dependence of the action potential duration
      on intracellular ATP concentration was estimated, without relying on a
      mathematical model of the cell membrane. The results imply that KATP-dependent
      action potential shortening is likely to occur if ATP concentration falls below
      normal levels (approximately 5 mM), as may happen regionally, or globally, during
      myocardial ischemia.

PMID- 1984870
TI  - Delayed end ejection increases isovolumic ventricular relaxation rate in isolated
      perfused canine hearts.
AB  - We sought to determine the ejection variables that are principally responsible
      for increases in isovolumic ventricular relaxation rate observed with increases
      in stroke volume. In nine isolated canine hearts, left ventricular ejection was
      controlled by patterns specially designed to isolate the ejection parameters most
      critical to isovolumic relaxation rate. When stroke volume was augmented by
      increases in end-diastolic volume (EDV) with end-systolic volume (ESV) held
      constant, isovolumic ventricular relaxation rate was unchanged, as gauged by the
      time constants of single-exponential fits to decaying pressure. In contrast, when
      ESV was decreased with EDV held constant, isovolumic relaxation time constants
      decreased significantly, from approximately 100 to 70 msec (protocol I). The
      important difference in these two situations might have been that the time of end
      ejection was delayed in the case with faster isovolumic relaxation. To rule out
      other parameters that may have influenced isovolumic relaxation, ejection
      velocity was varied in another protocol (protocol II) by either delays in time of
      the onset of ejection or advances in end-ejection time, always with constant ESV
      and EDV. Here isovolumic relaxation was progressively slowed as end ejection
      occurred earlier, whereas isovolumic relaxation rate was insensitive to changes
      in the onset of ejection, consistent with the unique importance of end ejection
      to isovolumic relaxation. In fact, our analysis reveals the remarkable finding
      that changes in isovolumic relaxation time constant produced by either protocol I
      or protocol II could be related quantitatively to end ejection by a single
      curve.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1984869
TI  - Mechanisms of angiotensin II- and arginine vasopressin-induced increases in
      protein synthesis and content in cultured rat aortic smooth muscle cells.
      Evidence for selective increases in smooth muscle isoactin expression.
AB  - Previous studies from this laboratory have demonstrated that angiotensin II (Ang
      II) and arginine vasopressin (AVP) are potent hypertrophic agents in cultured rat
      aortic smooth muscle cells. The present study identified major proteins that
      accumulate in Ang II-induced and AVP-induced hypertrophic cells and initiated
      studies of the mechanisms that contribute to their accumulation. Smooth muscle
      cell hypertrophy induced by Ang II and/or AVP (1 microM each) was associated with
      widespread increases in the content of many cellular proteins that were resolved
      by one- and two-dimensional gel electrophoresis. However, increases were also
      selective in nature, with increases in certain individual proteins, including
      actin (twofold to threefold), vimentin (2.5-fold to sevenfold), tropomyosin
      (threefold to sixfold), and myosin heavy chain, far exceeding overall increases
      in cellular protein content (20-40%). Increases in actin content were due largely
      to increased expression of smooth muscle alpha-actin (3.6- to 7.5-fold), as
      opposed to nonmuscle beta-actin (1.7- to 2.5-fold). Increases in smooth muscle
      alpha-actin were accompanied by a fivefold to eightfold increases in smooth
      muscle alpha-actin mRNA, indicating that these changes were not due exclusively
      to translational controls. Results demonstrate that contractile agonist-induced
      hypertrophy in cultured smooth muscle cells is due, in part, to increased
      expression of smooth muscle contractile proteins. Furthermore, the fact that Ang
      II and AVP induced selective increases in smooth muscle alpha-actin suggests that
      these agonists may not only regulate growth of vascular smooth muscle but may
      also promote expression of smooth muscle-specific contractile proteins during
      differentiation of vascular smooth muscle.

PMID- 1984871
TI  - Significance of the number of stimuli to initiate ouabain-induced arrhythmias in
      the intact heart.
AB  - Ouabain-induced arrhythmias are a well-known model used to study triggered
      activity resulting from delayed afterdepolarizations. In the intact heart,
      initiation of these arrhythmias is promoted by pacing, especially at fast rates.
      However, the relevance of the number of stimuli is unknown. In conscious dogs
      with formalin-induced atrioventricular block, we investigated the effect of
      variations in pacing mode on 1) the behavior of nonsustained triggered rhythms at
      progressive levels of ouabain intoxication, and 2) the induction of sustained
      ventricular tachycardia (VT). Twenty experiments were analyzed. Ouabain was
      administered as a bolus of 40 micrograms/kg followed by continuous infusion.
      Every 15 minutes the pacing protocol was repeated, with a maximum of 10, until
      completion or induction of VT. When VT could not be initiated, the experiment was
      repeated at least 1 week later, adding 5-10 micrograms/kg ouabain to the bolus
      and increasing the infusion rate correspondingly. This was repeated until VT
      could be induced. Four interstimulus intervals (200, 400, 600, and 800 msec) and
      seven numbers of stimuli (5, 10, 20, 35, 50, 100, and 150) were given in two
      pacing protocols. The effect of these protocols on 1) the number of induced beats
      per stimulation train, 2) their first postpacing interval, and 3) induction of VT
      were studied. Initiation of VT occurred after 75 +/- 42 minutes. The bolus of
      ouabain needed to induce VT was inversely related to the body weight of the
      animals. Progression of ouabain intoxication resulted in 1) a significant
      increase in the number of induced beats per stimulation train and 2) a
      significant shortening of the first postpacing interval. Stimulation at a faster
      rate and/or more stimuli resulted in 1) a significantly pronounced increase in
      the number of induced beats at the higher levels and 2) a significantly shorter
      first postpacing interval at successive levels of ouabain intoxication.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1984872
TI  - Effect of preconditioning ischemia on reperfusion arrhythmias after coronary
      artery occlusion and reperfusion in the rat.
AB  - Severe arrhythmias occur predictably on reperfusion after 5 minutes of coronary
      occlusion in the rat. There is little data available on whether ischemic
      preconditioning (PC) of hearts can reduce the incidence of such arrhythmias. The
      effect of PC (three cycles of 2 minutes of coronary occlusion and 5 minutes of
      reperfusion) on development of arrhythmias after a subsequent 5-minute coronary
      artery occlusion and reperfusion was studied. Rats (n = 16 each group) underwent
      5-minute occlusion and reperfusion alone or preceded by PC; arrhythmias were
      monitored during ischemia and for 10 minutes of reperfusion, and biopsies were
      taken for creatine phosphate and adenosine triphosphate in ischemic and
      nonischemic zones of the left ventricle. PC reduced the incidence of ventricular
      tachycardia (VT) during occlusion (81% control versus 13% PC, p less than 0.001).
      On subsequent reperfusion, ventricular fibrillation (VF) developed in zero PC
      animals versus 13 (81%) of controls (p less than 0.001), and irreversible VF in
      zero of PC versus seven (44%) of controls (p = 0.007). VT occurred in four (25%)
      of PC versus all (100%) of controls (p less than 0.001). PC reduced mean duration
      of VT plus VF from 320 +/- 54 to 5 +/- 1 seconds (p less than 0.001) and delayed
      arrhythmia onset from 8 +/- 2 to 85 +/- 35 seconds after reperfusion. There was
      no difference in creatine phosphate levels in the ischemic zone at the end of
      reperfusion in PC animals compared with controls without irreversible VF (16.2 +/
      4.1 versus 15.5 +/- 3.9 nmol/mg protein, p = NS).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1984873
TI  - Mechanical alternans during acidosis in ferret heart muscle.
AB  - Acidosis leads to mechanical alternans (i.e., alternation of large and small
      contractions) in ferret papillary muscles. This alternation in the size of the
      contraction is paralleled by alternation in the size of the intracellular Ca2+
      transient (monitored using the photoprotein aequorin). In isolated myocytes, the
      large contraction is accompanied by a prolonged action potential. Mechanical
      alternans also can be induced by acidosis in isolated myocytes during a train of
      voltage-clamp pulses. Thus, it appears unlikely that the mechanical alternans is
      secondary to changes in action potential duration; it is more likely that the
      observed changes in action potential duration are secondary to changes in the
      size of the Ca2+ transient. The observation that a Ca2(+)-activated inward
      current also shows alternation during mechanical alternans provides a possible
      mechanism for the link between Ca2+ and action potential duration. The
      alternation in the size of the Ca2+ transient may be secondary to the slowed
      mechanical restitution observed in papillary muscles during acidosis. This also
      could explain the observation that decreasing stimulation rate can abolish the
      alternans.

PMID- 1984874
TI  - Isoproterenol antagonizes prolongation of refractory period by the class III
      antiarrhythmic agent E-4031 in guinea pig myocytes. Mechanism of action.
AB  - The mechanism by which isoproterenol (ISO) prevents the prolongation of action
      potential duration (APD) and refractory period (RP) by the class III
      antiarrhythmic agent E-4031 was studied. E-4031 (1 microM) increased RP by 50%
      with no effect on contractile force in papillary muscles isolated from guinea pig
      heart. ISO (1 microM) increased force of contraction more than fivefold and
      decreased RP by 25%. The prolongation of RP by E-4031 was prevented by
      pretreatment of muscles with ISO. The prolongation of APD in isolated guinea pig
      ventricular myocytes by 5 microM E-4031 also was antagonized by prior exposure of
      the cells to 1 microM ISO. Instantaneous currents and delayed rectifier K+
      currents, IK, were measured in isolated myocytes using the suction microelectrode
      voltage-clamp technique. Currents were measured in response to 225-msec
      depolarizing pulses from a holding potential of -40 mV. Previous studies have
      demonstrated that IK in these cells results from activation of two distinct
      outward K+ currents, IKs and IKr (specifically blocked by E-4031). ISO doubled
      the magnitude of IKs without significant effect on IKr. The instantaneous
      current, putatively identified as a Cl- current, also was doubled by ISO but was
      unaffected by E-4031. The augmented conductance of IKs and instantaneous current
      by ISO results in a decrease in RP. The small effect of E-4031 on APD and RP in
      the presence of ISO results from the smaller contribution of IKr relative to the
      augmented repolarizing currents.

PMID- 1984875
TI  - Two arterial effective reflecting sites may appear as one to the heart.
AB  - The relation between reflected waves and features of ascending aortic pressure
      waveforms and impedance patterns was investigated with a modified T-tube model of
      the systemic arterial circulation. Ascending aortic pressure and flow and
      descending aortic flow were measured in 10 dogs under basal conditions and under
      the effect of an agent (methoxamine) that caused vasoconstriction and an increase
      of mean aortic pressure. A broad range of aortic pressure amplitudes and features
      was obtained. These waveshapes were classified into four groups. Under basal
      conditions, cases for which a prominent diastolic fluctuation was present (n = 8)
      were grouped in A. Cases for which this fluctuation was absent (n = 2) were
      grouped in B. Groups C (n = 4) and D (n = 3) included cases that, under
      vasoconstricted conditions, did or did not display, respectively, a diastolic
      fluctuation in pressure. Arterial T-tube model parameters were estimated by
      simultaneously fitting the model to both ascending and descending aortic flow
      with aortic pressure as input. A good fit was obtained in any case considered.
      After parameter estimation, forward and reflected waves and impedance patterns at
      the entrance of head circulation (head and upper limbs) and body circulation
      (trunk and lower limbs) as well as their merger in the ascending aorta were
      determined. T-tube input impedance compared well with impedance data points
      obtained from the ratio of corresponding harmonics of ascending aortic pressure
      and flow. In some cases (group A), modulus and phase spectra displayed two
      distinct minima, in the range from 0 to 10 Hz. In some other circumstances, these
      minima were less distinct (groups B and C) and could even appear as one (group
      D). Whether one or two minima appeared in the ascending aortic impedance spectra
      at low frequency and whether a prominent diastolic fluctuation did or did not
      appear in aortic pressure, pressure and flow waveshapes proximal to the heart
      were explained by the presence of two effective reflecting sites in the systemic
      circulation. In group B, a diastolic fluctuation in pressure was absent despite
      the fact that head-end and body-end reflected waves were distinct. This happened
      because body-end reflected waves peaked corresponding to a minimum of the head
      end reflected wave. In group D, a diastolic fluctuation in aortic pressure was
      absent because the body-end reflected wave moved into systole and superimposed on
      the head-end reflected wave. This superimposition was due to increased pulse wave
      velocity in the body transmission path as a result of decreased arterial
      distensibility.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1984876
TI  - Passive smoking and heart disease. Epidemiology, physiology, and biochemistry.
AB  - The evidence that ETS increases risk of death from heart disease is similar to
      that which existed in 1986 when the US Surgeon General concluded that ETS caused
      lung cancer in healthy nonsmokers. There are 10 epidemiological studies,
      conducted in a variety of locations, that reflect about a 30% increase in risk of
      death from ischemic heart disease or myocardial infarction among nonsmokers
      living with smokers. The larger studies also demonstrate a significant dose
      response effect, with greater exposure to ETS associated with greater risk of
      death from heart disease. These epidemiological studies are complemented by a
      variety of physiological and biochemical data that show that ETS adversely
      affects platelet function and damages arterial endothelium in a way that
      increases the risk of heart disease. Moreover, ETS, in realistic exposures, also
      exerts significant adverse effects on exercise capability of both healthy people
      and those with heart disease by reducing the body's ability to deliver and
      utilize oxygen. In animal experiments, ETS also depresses cellular respiration at
      the level of mitochondria. The polycyclic aromatic hydrocarbons in ETS also
      accelerate, and may initiate, the development of atherosclerotic plaque. Of note,
      the cardiovascular effects of ETS appear to be different in nonsmokers and
      smokers. Nonsmokers appear to be more sensitive to ETS than do smokers, perhaps
      because some of the affected physiological systems are sensitive to low doses of
      the compounds in ETS, then saturate, and also perhaps because of physiological
      adaptions smokers undergo as a result of long-term exposure to the toxins in
      cigarette smoke. In any event, these findings indicate that, for cardiovascular
      disease, it is incorrect to compute "cigarette equivalents" for passive exposure
      to ETS and then to extrapolate the effects of this exposure on nonsmokers from
      the effects of direct smoking on smokers. These results suggest that heart
      disease is an important consequence of exposure to ETS. The combination of
      epidemiological studies with demonstration of physiological changes with exposure
      to ETS, together with biochemical evidence that elements of ETS have significant
      adverse effects on the cardiovascular system, leads to the conclusion that ETS
      causes heart disease. This increase in risk translates into about 10 times as
      many deaths from ETS-induced heart disease as lung cancer; these deaths
      contribute greatly to the estimated 53,000 deaths annually from passive smoking.
      This toll makes passive smoking the third leading preventable cause of death in
      the United States today, behind active smoking and alcohol.

PMID- 1984878
TI  - Clinical experience with the Palmaz-Schatz coronary stent. Initial results of a
      multicenter study.
AB  - Stenting of native coronary arteries with a balloon-expandable stent was
      attempted in 226 patients after elective angioplasty. Delivery of the device was
      successful in 213 (94%) of the patients. Of these, 39 received aspirin and
      dipyridamole only (group 1) and 174 received aspirin, dipyridamole, and warfarin
      for 1-3 months (group 2). There was no abrupt closure (less than or equal to 1
      day) or perioperative death in either group. In-hospital or perioperative
      complications in group 1 compared with group 2 were as follows: subacute closure
      (1-14 days), seven (18%) patients versus one (0.6%) patient, respectively, p less
      than 0.0001; myocardial infarction, five (13%) patients versus one (0.6%)
      patient, respectively; condition requiring urgent bypass surgery, one (2.5%)
      patient versus no patients, respectively. Thus, the incidence of major
      complications such as death, myocardial infarction, or a condition requiring
      urgent bypass surgery was 15% in group 1 and 0.6% in group 2. Clinical follow-up
      revealed that 92% of the patients were asymptomatic at 3 months after stenting
      compared with 6% before stenting (p less than 0.0001). Of the 13 patients who
      were symptomatic, nine underwent cardiac catheterization and, ultimately,
      successful elective coronary angioplasty or bypass surgery. We conclude that a
      high delivery success rate can be expected with this device and that clinical
      thrombosis is less frequent in anticoagulated patients than in nonanticoagulated
      patients. Furthermore, in this selected patient population, coronary stenting
      results in a low incidence of in-hospital and perioperative complications.
      Clinical success, defined by absence of symptoms, appears to be sustained at 3
      months.

PMID- 1984877
TI  - Multicenter patency trial of intravenous anistreplase compared with streptokinase
      in acute myocardial infarction. The TEAM-2 Study Investigators.
AB  - Thrombolytic therapy has been shown to improve clinical outcome when administered
      early after the onset of symptoms of acute myocardial infarction; the mechanism
      of benefit is believed to be reestablishment and maintenance of coronary artery
      patency. Anistreplase is a second generation thrombolytic agent that is easily
      administered and has a long duration of action. To compare anistreplase (30
      units/2-5 min) and therapy with the Food and Drug Administration-approved regimen
      of intravenous streptokinase (1.5 million units/60 min), a randomized, double
      blind, multicenter patency trial was undertaken in 370 patients less than 76
      years of age with electrocardiographic ST segment elevation who could be treated
      within 4 hours of symptom onset. Coronary patency was determined by reading, in a
      blinded fashion, angiograms obtained early (90-240 minutes; mean, 140 minutes)
      and later (18-48 hours; mean, 28 hours) after beginning therapy. Early total
      patency (defined as Thrombolysis in Myocardial Infarction grade 2 or 3 perfusion)
      was high after both anistreplase (132/183 = 72%) and streptokinase (129/176 =
      73%) therapy, and overall patency patterns were similar, although patent arteries
      showed "complete" (grade 3) perfusion more often after anistreplase (83%) than
      streptokinase (72%) (p = 0.03). Similarly, residual coronary stenosis, determined
      quantitatively by a validated computer-assisted method, was slightly less in
      patent arteries early after anistreplase (mean stenosis diameter, 74.0%) than
      streptokinase (77.2%, p = 0.02). In patients with patent arteries without other
      early interventions, reocclusion risk within 1-2 days was defined
      angiographically and found to be very low (anistreplase = 1/96, streptokinase =
      2/94). Average coronary perfusion grade was greater, and percent residual
      stenosis was less, at follow-up than on initial evaluation and did not differ
      between treatment groups. Enzymatic and electrocardiographic evolution was not
      significantly different in the two groups. Despite rapid injection, anistreplase
      was associated with only a small (4-5 mm Hg), transient (at 5-10 minutes) mean
      differential fall in blood pressure. In-hospital mortality rates were comparable
      for anistreplase and streptokinase (5.9%, 7.1%). Stroke occurred in one (0.5%)
      and three (1.6%) patients, respectively; one stroke was hemorrhagic. Other
      serious bleeding events and adverse experiences occurred uncommonly and with
      similar frequency in the two groups. Thus, for the end points of our study
      (patency, safety), anistreplase and streptokinase showed overall favorable and
      relatively comparable outcomes, with a few differences.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 1984879
TI  - Detection of patients at risk for paroxysmal atrial fibrillation during sinus
      rhythm by P wave-triggered signal-averaged electrocardiogram.
AB  - To determine whether patients at risk for paroxysmal atrial fibrillation could be
      detected while in sinus rhythm, the signal-averaged electrocardiogram triggered
      by P waves was recorded in 42 patients with paroxysmal atrial fibrillation (Paf
      group) and in 50 control patients. The root mean square voltages (LP10, LP20, and
      LP30) for the last 10, 20, and 30 msec and the duration (Ad) of filtered (40-300
      Hz) P wave of the spatial magnitude were measured. LP10 and LP20 were
      significantly lower in the Paf than in the control group (LP10, 1.92 +/- 0.58
      versus 2.49 +/- 0.78 microV, p less than 0.001; LP20, 2.47 +/- 0.78 versus 3.46
      +/- 1.20 microV, p less than 0.0001), although no significant difference in LP30
      was found between groups. Ad was also significantly longer in the Paf than in the
      control group (137.0 +/- 14.3 versus 118.6 +/- 11.3 msec, p less than 0.001).
      These differences between the Paf and control groups remained significant even
      after dividing by the presence or absence of organic heart diseases. The criteria
      of "LP20 = 3.5 microV or less" and "Ad greater than 120 msec" as defining "atrial
      late potential" gave a sensitivity of 91% and a specificity of 76%. These
      findings suggest that patients at risk for paroxysmal atrial fibrillation could
      be detected while in sinus rhythm by using the P wave-triggered signal-averaged
      electrocardiogram.

PMID- 1984881
TI  - Doppler echocardiographic assessment of the St. Jude Medical prosthetic valve in
      the aortic position using the continuity equation.
AB  - To test whether the continuity equation can be applied to the noninvasive
      assessment of prosthetic aortic valve function, Doppler echocardiography was
      performed in 67 patients (mean age, 58 +/- 14 years) within 10 +/- 6 days after
      valve replacement with St. Jude Medical valves. All patients were clinically
      stable and without evidence of valve dysfunction. Valve size ranged from 19 to 31
      mm, and ejection fraction ranged from 30% to 75%. With the parasternal long-axis
      view, the left ventricular outflow diameter measured just proximal to the
      prosthetic valve correlated well with valve size (r = 0.92). Doppler-derived
      maximal gradients ranged from 9 to 71 mm Hg. Effective prosthetic aortic valve
      area by the continuity equation ranged between 0.73 cm2 for a 19-mm valve and
      4.23 cm2 for a 31-mm valve. With analysis of variance, effective orifice area
      differentiated various valve sizes (p less than 10(-14)) better than did
      gradients alone (p = 0.003) and correlated better with actual valve orifice area
      (r = 0.83 versus - 0.40). A Doppler velocity index, the ratio of peak velocity in
      the left ventricular outflow to that of the aortic jet, averaged 0.41 +/- 0.09
      and was less dependent on valve size (r = 0.43). Thus, the continuity equation
      can be applied to the assessment of prosthetic St. Jude valves in the aortic
      position. By accounting for flow through the valve, it provides an improved
      assessment over the sole use of gradients in the evaluation of prosthetic valve
      function.

PMID- 1984880
TI  - Sex differences in high density lipoprotein cholesterol among low-level alcohol
      consumers.
AB  - The purpose of this study was to examine high density lipoprotein cholesterol
      (HDL-C) levels in a sample of community-living women and men who consumed 1 drink
      of alcohol/day or less. Self-reports of alcohol consumption and clinical
      assessments of plasma lipid and lipoprotein levels were obtained twice, at 12
      months apart. Among men, consumption of 1 drink/day or less was unrelated to
      levels in HDL-C. In contrast, among women alcohol consumption throughout this
      relatively low consumption range was positively associated with HDL-C levels.
      These findings indicate that the association of alcohol and higher levels of HDL
      C may occur at lower intakes of alcohol in women than in men.

PMID- 1984882
TI  - Reduction of myocardial reperfusion injury by intravenous adenosine administered
      during the early reperfusion period.
AB  - Adenosine influences the function of several cell types thought to be involved in
      the pathogenesis of myocardial reperfusion injury. We have previously
      demonstrated that intracoronary administration of adenosine enhances myocardial
      salvage 24 hours after reperfusion. To determine if these beneficial effects
      could be obtained during a prolonged period of reperfusion using an intravenous
      route of administration, 22 closed-chest dogs were subjected to 90 minutes of
      proximal left anterior descending coronary artery occlusion and 72 hours of
      reperfusion. Animals randomly received either intravenous adenosine (0.15
      mg/kg/min) or an equal volume of Ringer's lactate during the first 150 minutes of
      reperfusion. The area at risk was defined in vivo with Monastral blue, and
      infarct size was measured histologically with Mallory's trichrome stain. Serial
      global and regional ventricular function were determined with contrast
      ventriculography and analyzed using a computerized radial shortening method.
      Biopsies were obtained from the central ischemic zone to assess endothelial
      ultrastructure and capillary obstruction. No significant effects in heart rate or
      blood pressure were noted during adenosine infusion. Transmural collateral blood
      flow during ischemia was similar in the groups. Infarct size expressed as a
      percentage of the anatomical area at risk was significantly less in the adenosine
      treated group (35.3 +/- 4.3% in controls versus 17.1 +/- 4.3% in treated animals,
      p less than 0.01). A progressive decrease in transmural blood flow was noted in
      control animals during reperfusion, resulting in a significant reduction at 3
      hours compared with the preocclusion value (0.69 +/- 0.11 ml/min/g [at baseline
      versus 0.45 +/- 0.10 ml/min/g at 3 hours, p less than 0.05]). In contrast, flow
      in adenosine animals at 3 hours was similar to baseline values (0.91 +/- 0.15
      ml/min/g at baseline versus 0.98 +/- 0.14 ml/min/g at 3 hours, p = NS) and was
      significantly higher (p less than 0.05) than the control group. Radial shortening
      in the ischemic zone was significantly improved at 3 (-2.6 +/- 2.8% in controls
      versus 11.6 +/- 3.3% in treated animals, p less than 0.01) and 72 hours (5.5 +/-
      2.0% in controls versus 17.3 +/- 3.5% in treated animals, p less than 0.01) after
      reperfusion in treated animals. Electron microscopy showed reduced neutrophil and
      erythrocyte plugging of capillaries with relative preservation of endothelial
      cell structure in the adenosine group.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1984883
TI  - Identification of viable myocardium in patients with chronic coronary artery
      disease and left ventricular dysfunction. Comparison of thallium scintigraphy
      with reinjection and PET imaging with 18F-fluorodeoxyglucose.
AB  - In patients with chronic coronary artery disease and left ventricular
      dysfunction, the distinction between ventricular dysfunction arising from
      myocardial fibrosis and ischemic, but viable, myocardium has important clinical
      implications. By positron emission tomography (PET), enhanced fluorine-18-labeled
      fluorodeoxyglucose (FDG) uptake in myocardial segments with impaired function and
      reduced blood flow is evidence of myocardial viability. Reinjection of thallium
      201 at rest immediately after stress-redistribution imaging may also provide
      evidence of myocardial viability by demonstrating thallium uptake in regions with
      apparently "irreversible" defects. To compare these two methods, we studied 16
      patients with chronic coronary artery disease and left ventricular dysfunction
      (ejection fraction, 27 +/- 9%), all of whom had irreversible defects on standard
      exercise-redistribution thallium single-photon emission computed tomography
      (SPECT) imaging. Thallium was reinjected immediately after the redistribution
      study, and SPECT images were reacquired. The patients also underwent PET imaging
      with FDG and oxygen-15-labeled water. A total of 432 myocardial segments were
      analyzed from comparable transaxial tomograms, of which 166 (38%) had
      irreversible thallium defects on redistribution images before reinjection. FDG
      uptake was demonstrated in 121 (73%) of these irreversible defects. Irreversible
      defects were then subgrouped according to the degree of thallium activity,
      relative to peak activity in normal regions. Irreversible defects with only mild
      (60-85% of peak activity) or moderate (50-59% of peak) reduction in thallium
      activity were considered viable on the basis of FDG uptake in 91% and 84% of
      these segments, respectively. In contrast, in irreversible defects with severe
      reduction in thallium activity (less than 50% of peak), FDG uptake was present in
      51% of segments. In such severe defects, an identical number of segments (51%)
      demonstrated enhanced uptake of thallium after reinjection. In these severe
      "irreversible" defects, data on myocardial viability were concordant by the two
      techniques in 88% of segments, with 45% identified as viable and 43% identified
      as scar on both PET and thallium reinjection studies. These observations suggest
      that thallium imaging can be used to identify viable myocardium in patients with
      chronic coronary artery disease and left ventricular dysfunction. Most
      irreversible defects with only mild or moderate reduction in thallium activity
      represent viable myocardium as confirmed by FDG uptake.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 1984885
TI  - Reentrant ventricular arrhythmias in the late myocardial infarction period:
      mechanism by which a short-long-short cardiac sequence facilitates the induction
      of reentry.
AB  - The electrophysiological mechanism by which a short-long-short stimulated cardiac
      sequence facilitates the induction of ventricular tachyarrhythmia was
      investigated in dogs 4 days after ligation of the left anterior descending
      coronary artery. In these dogs, reentry develops in the surviving
      electrophysiologically abnormal epicardial layer that overlies the infarct zone
      when premature stimulation results in a critically long arc of functional
      conduction block. The activation wavefront circulates around both ends of the
      arc, coalesces, and conducts slowly distal to the arc before reactivating sites
      proximal to the arc to initiate a figure-eight reentrant circuit. Epicardial
      isochronal activation maps and effective refractory periods (ERPs) were
      determined during three different stimulation protocols: A, a basic train of
      eight beats at a cycle length of 300 msec followed by a single premature stimulus
      (S2); B, a basic train of eight beats at a cycle length of 300 msec with abrupt
      lengthening of the last cycle of the train before S2 to 600 msec; C, a basic
      train of eight beats at a cycle length of 600 msec followed by S2. Protocol B was
      found to result in a differential lengthening of ERP at adjacent sites within the
      border of the epicardial ischemic zone, whereas protocols A and C induced,
      respectively, comparable shortening and lengthening of ERPs at the same sites.
      The differential lengthening of ERPs at adjacent sites resulted in an increased
      dispersion of refractoriness so that a premature stimulus induced functional
      conduction block between those sites. The development of a longer arc of
      conduction block and, hence, a longer reentrant pathway as well as slower
      conduction of the circulating wavefront during protocol B allowed more time for
      refractoriness to expire proximal to the arc and for the circulating wavefront to
      reexcite those sites to initiate reentry. The lengthening of ERP, associated with
      a single long cycle (protocol B), ranged from 44% to 79% of the total increase in
      ERP after a series of eight long cycles (protocol C). Epicardial sites with
      longer ERPs located close to the center of the ischemic zone showed more
      lengthening of refractoriness during protocol B compared with more normal sites
      near the border of the ischemic zone. This strongly suggests that the increased
      dispersion of refractoriness during protocol B is caused by the shorter memory of
      ischemic myocardium to the cumulative effects of preceding cycle lengths.

PMID- 1984884
TI  - Analysis of baroreflex control of heart rate in conscious dogs with pacing
      induced heart failure.
AB  - The autonomic components of the baroreflex control of heart rate were evaluated
      in conscious mongrel dogs before and after 4-6 weeks of ventricular pacing (250
      beats/min). Arterial baroreflex sensitivity (BRS) was determined by the slopes of
      linear regression of pulse interval versus the preceding systolic arterial
      pressure in response to bolus injections of either phenylephrine or
      nitroglycerin. BRS was significantly depressed in the heart failure state
      [nitroglycerin slope, 5.0 +/- 2.7 (mean +/- SD) versus 16.6 +/- 5.1 msec/mm Hg, p
      less than 0.005; phenylephrine slope, 15.0 +/- 14.8 versus 32.0 +/- 26.7 msec/mm
      Hg, p less than 0.005]. There was no depression in BRS in dogs that were used as
      time controls or were acutely paced for 30 minutes. After beta 1-adrenergic
      blockade with metoprolol, the resting heart rate in the heart failure state was
      depressed more than in the normal state (-17.0 +/- 5.0% versus -3.2 +/- 3.4%, p
      less than 0.001). Atropine significantly increased resting heart rate more in the
      normal state than in the heart failure state (115.8 +/- 36.7% versus 25.4 +/-
      14.5%, p less than 0.005). Thus, dogs in the heart failure state appear to have
      high resting cardiac sympathetic tone and low resting vagal tone. For
      nitroglycerin administration, metoprolol depressed BRS by 47.6 +/- 26.3% in the
      normal state and by 63.6 +/- 58.5% in the heart failure state. Atropine decreased
      the BRS by 86.7 +/- 7.8% in the normal state and by 39.5 +/- 30.2% in the heart
      failure state.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1984886
TI  - In vitro and in vivo effects within the coronary sinus of nonarcing and arcing
      shocks using a new system of low-energy DC ablation.
AB  - DC shocks within the coronary sinus have been abandoned because of the risk of
      cardiac rupture and tamponade. Catheter ablation using DC energy to electrodes
      straddling the ostium of the coronary sinus, when used clinically, has been
      reported to result in cardiac tamponade in as many as 16% of patients. A new
      system of energy delivery maximizes voltage while decreasing the undesirable
      effects caused by barotrauma. This system includes 1) a low-energy ablation power
      supply with a brief time-constant capacitive discharge that delivers up to 40 J
      and 3,000 V and 2) a low-energy ablation catheter with a contoured distal
      electrode. We performed in vitro and in vivo studies of this new system and
      compared arcing shocks with nonarcing shocks. Ablations were performed using
      unipolar distal shocks (D) and unipolar shocks to both electrodes made
      electrically common (P-D). In vitro studies were done in a large tank filled with
      physiological saline while recording voltage, current, and pressure. High-speed
      cinematography (32,000 frames/sec) of shocks of 10-40 J permitted detailed
      analysis of the vapor globe. Anodal shocks of less than 20 J showed no arcing or
      only minimal vapor globe formation. For D and P-D anodal shocks of 40 J, the
      diameters of the vapor globe were 31 and 22 mm, respectively, corresponding to
      pressure recordings of 11 and 4.9 atm. The pressure rise lasted less than 50 mu
      sec. In vivo studies involved 18 dogs that received nonarcing shocks (one to six
      shocks of 15 J) and 18 dogs that received arcing shocks (one to three shocks of
      40 J). Each group was divided between D and P-D shocks; catheter ablation was
      performed at a mean +/- SEM distance of 2.94 +/- 0.92 cm within the coronary
      sinus. All dogs tolerated the procedure without cardiac rupture or tamponade.
      When killed 2-4 days later, the dogs had edema and hyperemia or hemorrhage in the
      area of the coronary sinus. We compared the effects of multiple (three to six)
      nonarcing shocks with the effects of one to three arcing shocks. Disruption or
      rupture of the coronary sinus within the epicardial fat space occurred in two of
      12 dogs (17%) with multiple nonarcing shocks but in 13 of 18 dogs (72%) with
      arcing shocks (p less than 0.003). Occlusion of the coronary sinus occurred in
      two of 12 dogs (17%) with multiple nonarcing shocks and in nine of 18 dogs (50%)
      with arcing shocks (p less than 0.06).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1984887
TI  - Coronary vasodilator reserve. Comparison of the effects of papaverine and
      adenosine on coronary flow, ventricular function, and myocardial metabolism.
AB  - To evaluate coronary flow reserve during cardiac catheterization, intracoronary
      adenosine and papaverine have been used in the clinical setting. Although
      papaverine maximizes coronary blood flow, it induces several toxic side effects
      that reduce its desirability as a coronary dilator. This investigation was
      designed to compare the subselective intracoronary administration of papaverine
      with that of adenosine in an animal model. In dogs (n = 34), we studied the
      effects of each agent on hemodynamics, regional myocardial blood flow,
      contractility (sonomicrometric and echocardiographic), metabolism (coronary
      arterial and venous lactate and tissue high-energy phosphates), and
      electrocardiographic (ST and QT intervals) parameters. Barbiturate and morphine
      anesthesia/analgesia was induced, and a left thoracotomy was performed. An
      arterial shunt was created from the left carotid artery to the left anterior
      descending coronary artery. Two separate groups were studied: group 1 (n = 16)
      for regional myocardial blood flow and mechanical function and group 2 (n = 18)
      for biochemical measurements. Adenosine (67 +/- 2 micrograms/min) or papaverine
      (6 +/- 1 mg/min) was infused into the coronary shunt at a rate of 0.5 + 0.1
      ml/min for a maximum duration of 3.5 minutes. Regional myocardial blood flows
      were determined at control (predrug) and maximal coronary flow using radiolabeled
      microspheres. All hemodynamic, wall motion, biochemical, and electrocardiographic
      parameters were also measured at these times. Both drugs produced comparable
      increases in total and regional coronary blood flows (adenosine, 1.21 +/- 0.15 to
      4.83 +/- 0.36 ml/min/g; papaverine, 1.21 +/- 0.05 to 4.89 +/- 0.28 ml/min/g) upon
      infusion into the left anterior descending coronary artery. Papaverine produced
      significant (p less than 0.05) changes in subendocardial ST segment
      electrocardiogram (-2.5 mm), QT prolongation (8 +/- 2%), myocardial creatine
      phosphate (47% decrease), and coronary sinus serum lactate (277% increase)
      compared with control. In addition, intracoronary papaverine induced an abnormal
      contractile pattern. No significant changes in any of these parameters (i.e., ST
      segment, QT prolongation, myocardial creatine phosphate level, or lactate level)
      were observed with intracoronary adenosine infusions. We conclude that
      intracoronary adenosine is comparable to papaverine for maximizing coronary blood
      flow without the deleterious properties observed with intracoronary papaverine.

PMID- 1984888
TI  - Relation between maximum time-varying elastance pressure-volume areas and
      myocardial oxygen consumption in dogs.
AB  - To establish whether pressure-volume areas (PVAs) calculated using the maximum
      time-varying elastance (Emax) have a relation with myocardial oxygen consumption
      (MVO2) that improves on other indexes of myocardial oxygen demand, we studied
      nine dogs of either sex weighing 19-39 kg, which were instrumented with a
      micromanometer left ventricular (LV) catheter and a Wilton-Webster coronary sinus
      flow catheter and had red blood cells tagged with technetium-99m for radionuclide
      angiography. Hemodynamics, coronary sinus flow determinations, and radionuclide
      angiograms were obtained under control conditions and during three to five steady
      state loading conditions (mean +/- SD, 5.6 +/- 0.7). Isochronal pressure-volume
      data points from each pressure-volume loop were subjected to linear regression
      analysis to calculate Emax. The Emax relations, diastolic curves, and systolic
      portions of each pressure-volume loop were used to obtain calibrated PVAs. The
      Emax PVA (mm Hg.ml.beat-1.100 g-1) and MVO2 (ml O2.beat-1.100 g-1) values
      correlated in each animal (r = 0.77 to 0.99). Their slopes averaged (3.48 +/-
      1.68) x 10(-5) ml O2.mm Hg-1.ml-1, and their y-axis intercepts averaged 0.07 +/-
      0.04 ml O2.beat-1.100 g-1. When the MVO2 relations were compared with Emax PVA,
      LV systolic pressure-rate product, LV stroke work, and a modification of the LV
      pressure-work index, the Emax PVA, LV systolic pressure-rate product, and LV
      pressure-work index had similar relations with MVO2, whereas LV stroke work was a
      weaker index of MVO2 (p less than 0.05 versus Emax PVA). This occurred because
      the Emax PVA:MVO2 slopes and y-axis intercepts differed in each dog, which was
      due to differences in basal LV contractility. The Emax PVA:MVO2 slopes correlated
      with Emax (r = 0.73, p less than 0.05), and the y-axis intercepts were also
      weakly related to Emax (r = 0.48, p = 0.19). We conclude that the Emax PVAs
      calculated using data acquisition techniques that are clinically applicable have
      relations with MVO2 that in general do not improve on other indexes of myocardial
      oxygen demand in this animal preparation.

PMID- 1984889
TI  - Maladies attributed to myxomatous mitral valve.

PMID- 1984890
TI  - Myocardial viability. What does it mean and how do we measure it?

PMID- 1984891
TI  - Calcium channel blockers and congestive heart failure.

PMID- 1984892
TI  - Transesophageal echocardiography. New window to coronary arteries and coronary
      blood flow.

PMID- 1984893
TI  - Unstable angina. Quality of life.

PMID- 1984894
TI  - Case volume and clinical competence.

PMID- 1984896
TI  - Ischemic heart disease and platelet aggregation. The Caerphilly Collaborative
      Heart Disease Study.
AB  - The Caerphilly Collaborative Heart Disease Study is based on a large cohort of
      men (2,398) aged 49-66 years at the time of study. Platelet aggregation induced
      by collagen, thrombin, and ADP was measured in fasting blood samples and was
      related to prevalent angina, past myocardial infarction, and electrocardiographic
      evidence of ischemic heart disease. A number of subjects had taken aspirin, other
      nonsteroidal anti-inflammatory drugs, or other drugs affecting platelet
      aggregation 7 days before blood sample collection; after the exclusion of these
      subjects, data were available for 1,811 men. No relations were demonstrated with
      angina, but significant relations were shown between past myocardial infarctions
      and electrocardiographic evidence of ischemia and ADP-induced aggregation (both
      primary and secondary) and between electrocardiographic evidence of ischemia and
      thrombin-induced aggregation. The strongest relation indicated more than a
      twofold increase in the odds of a past myocardial infarction in subjects of the
      highest fifth of ADP-induced primary platelet aggregation compared with the
      lowest fifth. No significant relations were detected with collagen-induced
      aggregation. Accounting for a number of possible confounding factors had a
      relatively small impact on the relations between platelet aggregation and
      ischemic heart disease. Other evidence, including the well-established effect of
      aspirin on reducing the incidence of ischemic heart disease, indicates that the
      relations we describe are unlikely to be simply an effect of IHD on platelets.

PMID- 1984895
TI  - An updated coronary risk profile. A statement for health professionals.

PMID- 1984897
TI  - Myocardial infarction in Mexican-Americans and non-Hispanic whites. The San
      Antonio Heart Study.
AB  - Mexican-American men experience reduced cardiovascular mortality compared with
      non-Hispanic white men. There is no corresponding ethnic difference in
      cardiovascular mortality in women. The difference in men could result either from
      a lower incidence of cardiovascular disease or a lower case fatality rate among
      Mexican-Americans. Although the incidence of cardiovascular disease in Mexican
      Americans is unknown, we have collected data on prevalence of myocardial
      infarction in 5,148 individuals examined in the San Antonio Heart Study, a
      population-based survey of cardiovascular disease conducted between 1979 and 1988
      in Mexican-Americans and non-Hispanic whites aged 25-64 years. Myocardial
      infarction was assessed by Minnesota-coded electrocardiograms and by a self
      reported history of a physician-diagnosed heart attack. For both end points, the
      age-adjusted prevalence of myocardial infarction was lower in Mexican-American
      men than in non-Hispanic white men. After adjustment for age and diabetes status
      (present/absent), the odds of a myocardial infarction, as defined by either
      criterion, was approximately one third lower in Mexican-American men than in non
      Hispanic white men (p = 0.06). In women, the prevalence of both myocardial
      infarction end points was slightly higher in Mexican-Americans than in non
      Hispanic whites, although neither of these differences was significant. Although
      the ethnic differences in prevalence in this study were not statistically
      significant, their pattern parallels the pattern in the mortality due to
      cardiovascular diseases. Therefore, the results support the hypothesis that the
      reduced cardiovascular mortality rate observed in Mexican-American men reflects a
      lower incidence of myocardial infarction rather than a reduced case fatality rate
      because the latter would result in a higher prevalence.

PMID- 1984898
TI  - Diltiazem increases late-onset congestive heart failure in postinfarction
      patients with early reduction in ejection fraction. The Adverse Experience
      Committee; and the Multicenter Diltiazem Postinfarction Research Group.
AB  - The Multicenter Diltiazem Postinfarction Trial (MDPIT) reported no consistent
      diltiazem effect on new or worsened congestive heart failure (CHF) during 12-52
      months' follow-up after acute myocardial infarction. This was puzzling in light
      of the observation that patients with findings suggesting left ventricular
      dysfunction (LVD) at baseline on diltiazem had more cardiac events (cardiac
      mortality or recurrent nonfatal infarction) than such patients on placebo. We
      hypothesized that diltiazem increased the frequency of late CHF as well as of
      cardiac events, but only in patients predisposed by LVD. Using the same
      characterizing variables as the primary MDPIT analysis, we found that patients
      with pulmonary congestion, anterolateral Q wave infarction, or reduced ejection
      fraction (EF) at baseline were more likely to have CHF during follow-up than
      those without these markers of LVD. CHF was particularly frequent in the patients
      with LVD who were randomized to diltiazem. Among those with a baseline EF of less
      than 0.40, late CHF appeared in 12% (39/326) receiving placebo and 21% (61/297)
      receiving diltiazem (p = 0.004). Life table analysis in patients with an EF of
      less than 0.40 confirmed more frequent late CHF in those taking diltiazem (p =
      0.0017). In addition, the diltiazem-associated rise in the frequency of late CHF
      was progressively greater with increasingly severe decrements in baseline EF.
      This diltiazem effect was absent in patients with pulmonary congestion at
      baseline but an EF of 0.40 or more, suggesting a unique association between
      diltiazem-related late CHF and systolic LVD.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1984899
TI  - Transesophageal Doppler echocardiography evaluation of coronary blood flow
      velocity in baseline conditions and during dipyridamole-induced coronary
      vasodilation.
AB  - Transesophageal echocardiography allows the evaluation of proximal coronary
      artery anatomy and coronary blood flow velocity (CBFV). To assess the potential
      of transesophageal echocardiography in evaluating CBFV and its variations induced
      by coronary-active drugs, we studied 15 patients by high-quality pulsed wave
      Doppler recordings of CBFV. In these patients, transesophageal Doppler evaluation
      of CBFV was performed before, 2 minutes after cessation of dipyridamole infusion
      (0.56 mg/kg in 4 minutes), and 2 minutes after aminophylline infusion (240 mg
      injected 4 minutes after cessation of dipyridamole infusion). The following CBFV
      parameters were evaluated at each of the three steps of the study protocol:
      maximal and mean diastolic velocities and maximal and mean systolic velocities.
      Furthermore, the following indexes of coronary flow reserve were evaluated: the
      ratio between maximal diastolic velocity recorded after and before dipyridamole
      administration and the ratio between mean diastolic velocity recorded after and
      before dipyridamole administration. Nine of the 15 patients had a normal left
      anterior descending coronary artery (group A), whereas the remaining six had
      significant (less than or equal to 75%) stenosis (group B). In group A patients,
      all CBFV parameters increased significantly during dipyridamole infusion and
      returned to near baseline values after aminophylline infusion. In group B
      patients, on the other hand, none of the CBFV parameters increased after
      dipyridamole infusion. Dipyridamole/baseline maximal diastolic velocity and mean
      diastolic velocity ratios were, respectively, 3.22 +/- 0.96 and 3.04 +/- 0.88 in
      group A and 1.46 +/- 0.45 (p less than 0.01 versus group A) and 1.48 +/- 0.49 (p
      less than 0.01 versus group A) in group B patients.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1984901
TI  - Regurgitant jet size by transesophageal compared with transthoracic Doppler color
      flow imaging.
AB  - Combined echocardiography and Doppler color flow mapping from transthoracic
      imaging windows has become the standard method for the noninvasive assessment of
      valvular regurgitation. This study compared regurgitant jet areas by Doppler
      color flow imaging derived from the newer transesophageal approach with
      measurements obtained from conventional transthoracic apical views. Maximal
      regurgitant jet area determinations and an overall visual estimate of lesion
      severity were obtained from 42 patients who underwent color flow examination by
      both techniques. Seventy-three regurgitant lesions were visualized by
      transesophageal flow imaging: 34 mitral, 22 aortic, and 17 tricuspid jets.
      Transthoracic studies in the same patients revealed fewer regurgitant lesions for
      each valve; 20 mitral, 16 aortic, and 12 tricuspid (p = 0.0009). A comparison of
      maximal jet areas determined by transesophageal and transthoracic studies showed
      a good overall correlation (r = 0.85, SEE = 2.8 cm2) and a systematic
      overestimation by the transesophageal technique (TEE = 0.96 TTX + 2.7). For the
      subgroup with mitral insufficiency, valve lesions visualized by both techniques
      were larger by the transesophageal approach (n = 18, 6.0 versus 3.6 cm2, p =
      0.008). Semiquantitative visual grading of individual valve lesions by two
      independent observers revealed a higher grade of regurgitation with more jets
      classified as mild (38 versus 25), moderate (18 versus 13), and severe (17 versus
      10) by esophageal imaging than by transthoracic imaging. Thus, transesophageal
      color flow mapping techniques yield a higher prevalence of valvular regurgitation
      than do transthoracic techniques in the same patients. Jet area and the overall
      estimate of regurgitant lesion severity were also greater by transesophageal
      color Doppler imaging compared with standard transthoracic imaging.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1984900
TI  - Diagnosis of noninfective cardiac mass lesions by two-dimensional
      echocardiography. Comparison of the transthoracic and transesophageal approaches.
AB  - This study was conducted in 46 patients with cardiac thrombi, 15 patients with
      atrial myxomas, and 32 patients with other cardiac or paracardiac tumors.
      Diagnoses were subsequently proven by surgery, autopsy, computed tomography,
      magnetic resonance imaging, or angiography in all patients. All patients
      underwent precordial and transesophageal two-dimensional echocardiography to
      assess the various mass detection rates. Atrial myxomas and predominantly left
      sided cardiac tumors were identified by both echocardiographic techniques with
      comparable detection rates. Left ventricular apical thrombi were detected more
      frequently by precordial echocardiography. In contrast, transesophageal
      echocardiography was superior in visualizing left atrial appendage thrombi, small
      and flat thrombi in the left atrial cavity, thrombi and tumors in the superior
      vena cava, and masses attached to the right heart and the descending thoracic
      aorta. These data indicate that transesophageal echocardiography leads to a
      clinically relevant improvement of the diagnostic potential in patients in whom
      cardiac masses are suspected or have to be excluded in order to ensure the safety
      of clinical procedures.

PMID- 1984902
TI  - Exercise training improves left ventricular systolic function in older men.
AB  - To determine whether endurance exercise training can improve left ventricular
      systolic function in older men, 10 healthy sedentary men (64 +/- 3 years old;
      mean +/- SD) were studied. Training consisted of endurance exercise 4 +/- 0.3
      days per week for 11.8 +/- 2.5 months at a progressively increasing intensity of
      60-80% of maximal O2 uptake (Vo2max) with additional brief bouts of exercise
      equal to 93 +/- 13% of Vo2max. Vo2max increased from 29.6 +/- 4.1 to 37.2 +/- 5.7
      ml/kg/min (p less than 0.001). Percent body fat was decreased (17.8 +/- 3.6%
      versus 15.6 +/- 3.6%; p less than 0.001). Before training, left ventricular
      ejection fraction, determined by electrocardiographic-gated equilibrium blood
      pool imaging, increased only modestly during exercise (from 66.3 +/- 6.7% at rest
      to 70.6 +/- 6.9% at peak exercise). After training, the increase in ejection
      fraction during exercise was significantly greater (from 67 +/- 4.8% at rest to
      77.6 +/- 7.5% at peak exercise) than that observed before training and was
      similar to that in young sedentary men (64 +/- 7% at rest versus 74 +/- 9% at
      peak exercise). Although the changes in systolic pressure from rest to exercise
      were similar, end-systolic volume decreased significantly at peak exercise after
      (51 +/- 12 versus 38 +/- 13 ml; p less than 0.005) but not before (46 +/- 8
      versus 43 +/- 13 ml; p = NS) training with a shift in the end-systolic volume
      systolic blood pressure relation to the left compatible with enhanced inotropic
      state.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1984903
TI  - Symposium. Musculoskeletal tumors in children.

PMID- 1984904
TI  - Effects of radiation therapy on skeletal growth in childhood.
AB  - Ionizing radiation was used to treat childhood cancer long before the advent of
      chemotherapy, and it took little time for physicians to appreciate the
      deleterious effects it had on skeletal growth. The cause of this complication
      results predominantly from alteration of chondroblastic activity. This may stem
      directly from irradiation at the epiphyseal plate or indirectly from irradiation
      of glands that secrete growth-mediating hormones. The complication can go far
      beyond the obvious physical afflictions and extend into the psychologic domain,
      rendering deeper, more permanent scars. Presently, many of these effects are
      predictable, reducible, and treatable without compromising the cure that so often
      depends on the use of irradiation. Because of the complexities of childhood
      cancer therapy, strategies aimed at diminishing these effects are challenging. It
      is imperative that these effects be understood so that they can be reduced in
      current patients and prevented in future patients.

PMID- 1984905
TI  - Limb-salvage surgery in the treatment of osteosarcoma in skeletally immature
      individuals.
AB  - Sacrifice of major growth plates during resection and fixed-length reconstruction
      of a limb in a skeletally immature child with osteosarcoma may result in a
      significant limb-length inequality as growth progresses. A limb-length
      discrepancy in the humerus may cause minor cosmetic problems but does not
      generally result in a significant functional deficit. In the lower extremity,
      tumors about the knee, including the distal femur and proximal tibia, usually
      present the dilemma of whether limb salvage by arthrodesis, osteoarticular
      allograft, or endoprosthetic replacement would result in a significant limb
      length inequality and whether amputation of the extremity is a preferable
      procedure. The techniques of rotationplasty and an expandable endoprosthesis have
      been successfully used for treating skeletally immature patients with
      osteosarcoma of the distal femur. With regard to survival and function, the
      results obtained with these innovative methods are favorable compared with those
      of a high above-knee amputation.

PMID- 1984906
TI  - Osteolytic monostotic Paget's disease of the fifth lumbar vertebra. A case
      report.
AB  - Osteolytic monostotic Paget's disease or osteitis deformans of the fifth lumbar
      vertebra occurred in a 55-year-old woman. An isolated lytic process involving the
      entire vertebral body and posterior elements and an open biopsy showed extensive
      remodeling with cement lines, myelofibrosis, and osteoclastic resorption typical
      of Paget's disease.

PMID- 1984907
TI  - The cellular biology of bone tumors.
AB  - New knowledge in cell and molecular biology has begun to expand the understanding
      of the biology of osteosarcoma and Ewing's sarcoma. Studies on osteosarcomas have
      revealed abnormalities in the growth-inhibiting retinoblastoma gene, which may
      release cells from normal growth control. Abnormalities in growth factor
      production or response tend to inappropriately activate cell growth. Tumor cell
      DNA content and cytogenetics may affect the diagnosis and prognostic grouping of
      osteosarcomas. In Ewing's sarcomas, a characteristic translocation between
      Chromosomes 11 and 22 has been identified; this translocation is also found in
      malignant neuroepitheliomas. A variety of studies point to both neuroectodermal
      and mesenchymal origins for Ewing's sarcomas. Applications of new biologic
      knowledge and technology to clinical problems will lead to significant changes in
      the diagnosis, and perhaps in the treatment, of these tumors in the coming years.
      Collaborations between community and referral center physicians and scientists
      are critical for continued progress.

PMID- 1984908
TI  - Osteoid osteoma of the scapula. A case report and review of the literature.
AB  - The scapula is a rare location for osteoid osteoma, which in most cases does not
      involve the flat bones. The en bloc excision in this uncommon location can be
      problematic since the surgical exposure is difficult, and shoulder joint function
      can be affected if the lesion is subchondral. In an 18-year-old man, an osteoid
      osteoma was located in the subchondral area of the glenoid. A guided needle
      biopsy of the nidus resulted in complete healing. This mode of treatment, with
      proper follow-up examination, is acceptable for a benign lesion situated in a
      problematic location.

PMID- 1984909
TI  - Nonhemophilic hemosiderotic synovitis of the shoulder. A case report.
AB  - In a nonhemophilic 72-year-old man, a persistent degenerative hemarthrosis of the
      shoulder joint was associated with a complete tear of the rotator cuff.
      Extensive, rusty synovial pigmentation and hyperplasia (hemosiderotic synovitis)
      mimicking pigmented villonodular synovitis (PVS) were noted at surgery.
      Spontaneous hemarthrosis of the shoulder includes rapid onset of severe pain,
      limitation of movement, subsequent appearance of a bruise on the affected
      shoulder and arm, and radiological evidence of joint degeneration. Hemosiderotic
      synovitis results from chronic intraarticular bleeding. With the breakdown of
      trapped hemoglobin, iron-containing hemosiderin is stored in synovial tissue
      producing rusty discoloration and proliferative reaction. The classic
      cytoarchitecture of PVS has additional subsynovial nodular proliferation of
      mononuclear cells. Hemarthrosis may produce significant structural alteration of
      joints. Its prompt recognition and the awareness of underlying causes should lead
      to earlier diagnosis, appropriate therapy, less joint destruction, and better
      outcomes.

PMID- 1984910
TI  - Tuberculous tenosynovitis of the wrist. Two case reports.
AB  - Tuberculosis was first described in 1756 by Acrel in a case report. Subsequent
      reports of musculoskeletal tuberculosis documented the uncommon occurrence of
      hand and wrist involvement. The two cases presented here demonstrate the
      difficulty in eradicating the organism even with modern regimens of chemotherapy.
      Intraoperative Gram's stain and frozen sections were useful to rule out other
      etiologies. Firm diagnosis must be established by tissue culture. The first case
      appeared cured after thorough initial debridement and had no recurrence for 36
      years. While recurrences are common in patients treated with debridement alone,
      most appear within one year after the index procedure. The amount of time that
      elapsed in this case is unusual and serves as a sobering reminder that
      tuberculosis may recur at a time distant from the initial procedure. The second
      patient had tuberculosis diagnosed elsewhere and was treated twice with
      antituberculous chemotherapy. Although the first course of therapy for six months
      may have been inadequate, the second course with multiple drugs for 18 months
      would certainly be considered adequate; yet he had a recurrence in his wrist
      eight months after completing treatment. These two cases illustrate the
      fastidious nature of the Mycobacterium tuberculosis organism and the need for a
      combined treatment protocol of meticulous surgical debridement and combined
      chemotherapy.

PMID- 1984911
TI  - Extensor tendon rupture after osteoarthrosis of the wrist associated with
      nonrheumatoid positive ulnar variance.
AB  - Rupture of the extensor tendon after osteoarthrosis of the wrist associated with
      nonrheumatoid, positive ulnar variance is uncommon. Eight cases were seen in the
      last five years. They included five men and three women, whose ages ranged from
      54 to 82 years (average, 70 years). In all the cases, roentgenograms revealed
      osteoarthrotic changes in the wrist and dorsal subluxation or dislocation of the
      ulnar heads. Seven cases had operations. Friction with the dorsally subluxated or
      dislocated ulnar head and the osteophytes surrounding it caused these tendons to
      rupture. It was impossible to use end-to-end sutures, so tendon transfers or
      tendon grafts were performed. The patients were evaluated one to four years after
      surgery. Three patients complained of some disability in their daily lives,
      notably, limited flexion of their fingers. It is important that during surgery
      the reconstructed tendons should not be strained excessively.

PMID- 1984912
TI  - Treatment of scaphoid nonunion by radical curettage, trapezoidal iliac crest bone
      graft, and internal fixation with a Herbert screw.
AB  - Ten adult male patients with scaphoid nonunions were treated by radical
      curettage, trapezoidal iliac crest bone grafting, and internal fixation with a
      Herbert screw. The mean patient age was 24.7 years, and the mean duration of the
      nonunion before surgery was 37.3 months. Mean follow-up time was 30.4 months.
      Nine of the ten nonunions healed, although one patient required a second bone
      grafting procedure. The mean postoperative grip strength was 45.0 kg, and the
      mean postoperative pinch strength was 11.5 kg. The mean postoperative range of
      motion was volar flexion, 76.1 degrees; dorsiflexion, 74.2 degrees; radial
      deviation, 22.1 degrees; and ulnar deviation, 40.1 degrees. The scapholunate
      angle decreased from a mean of 72.8 degrees preoperatively to 60.6 degrees
      postoperatively (p less than 0.025). The mean carpal index was 0.57
      postoperatively. Mean scaphoid length increased postoperatively and was within
      0.2 mm of the opposite (normal) scaphoid in every patient except the single
      patient with a persistent nonunion (p less than 0.025). All patients returned to
      work (eight as laborers), and nine of ten wrists were subjectively rated as good
      or excellent. The results of the series suggests that treatment of displaced
      scaphoid nonunion by radical curettage, trapezoidal iliac crest bone grafting,
      and internal fixation with a Herbert screw is an effective method of treatment
      that reconstitutes scaphoid anatomy and promotes excellent wrist function.

PMID- 1984913
TI  - Ultrasound in the diagnosis of congenital dysplasia and dislocation of the hip
      joints in children older than two years.
AB  - To evaluate the use of ultrasound in the diagnosis to congenital dysplasia and
      dislocation of the hip (CDH) in children older than two years of age, 64 patients
      with normal hip joints and 47 patients with present or previous CDH were
      examined. Lateral and anterior ultrasound scanning was employed, and the coverage
      of the femoral head by the acetabular roof was assessed. The ultrasound
      measurements were compared with standard roentgenography, and a good accordance
      between the methods was found. A lateral projection of the femoral head in
      relation to the bony acetabular rim of more than 8 mm in children younger than
      ten years of age indicated subluxation and more than 15 mm at age two to four
      years indicated dislocation. Reliable images were obtained by ultrasound at any
      age between two and 18 years. Ultrasound is recommended as the primary imaging
      technique in the evaluation of hip joints, even in older children, and ultrasound
      should replace roentgenography in most of the follow-up examinations of children
      with previous CDH.

PMID- 1984914
TI  - Somatosensory-evoked potential monitored during total hip arthroplasty.
AB  - One hundred consecutive patients were monitored using somatosensory-evoked
      potential (SEP) monitoring to detect intraoperative sciatic nerve compromise
      during total hip arthroplasty. The peroneal nerve was stimulated using the
      contralateral extremity to rule out systemic influences on the SEP tracings. Loss
      of amplitude or an increase in latency of greater than 10% was considered
      significant. Of the 18 patients who exhibited changes that met these criteria, 16
      were female. Two patients had loss of amplitude of the tracings at the time of
      closure, and both of these patients exhibited postoperative sciatic nerve
      palsies. There were no false negatives. Femoral reaming and reduction are the
      surgical events most commonly associated with nerve reactions. Patients who have
      had prior hip procedures appear to be at higher risk. There was no correlation
      with intraoperative SEP changes and age, weight, surgical approach, or leg
      lengthening. Compared with unmonitored patients, there was no reduction in the
      incidence of sciatic palsy.

PMID- 1984915
TI  - Growth disturbance in Legg-Calve-Perthes disease and the consequences of surgical
      treatment.
AB  - Seventy-two patients with Legg-Calve-Perthes disease were studied to assess the
      interference with proximal femoral growth as a result of the disease itself and
      of surgical treatment. Twenty-five patients were treated nonoperatively, 20 were
      treated by femoral varus derotation osteotomy, and 27 by innominate osteotomy.
      All patients were studied clinically for evidence of abductor weakness and leg
      length discrepancy. They were also studied roentgenographically for evidence of
      femoral head deformity and trochanteric overgrowth. The overall results showed a
      6% incidence of leg-length discrepancy greater than 2 cm after both operative and
      nonoperative treatment. The articulo-trochanteric distance (ATD) was less than +5
      mm in 23% of patients, of which 43% had a positive Trendelenburg sign. A
      significantly lower mean ATD was found in patients treated by femoral varus
      osteotomy, which should be avoided in patients over eight years of age. The study
      also demonstrated a strong association between coxa magna and growth disturbance
      of the proximal femoral physis manifesting itself as either a leg-length
      discrepancy or as a low ATD. The significant effects of growth disturbance after
      treatment must be considered, as well as the sphericity of the healed femoral
      head, in the final assessment in Legg-Calve-Perthes disease.

PMID- 1984916
TI  - Bilateral femoral retroversion associated with acetabular dysplasia. A case
      report.
AB  - Retroversion of the proximal femur is associated with a number of acquired
      conditions but is unusual in a congenital form. It is even more unusual to be
      associated with acetabular dysplasia. A 38-year-old woman with bilateral hip pain
      had roentgenographic evidence of acetabular dysplasia with valgus neck-shaft
      angles. Physical findings were consistent with femoral retroversion, and computed
      tomography demonstrated 28 degrees of retroversion on both sides. Symptomatic
      relief was obtained with bilateral varus internal rotation osteotomies of the
      proximal femur. To date, a case of retroverted femora associated with acetabular
      dysplasia seems not to have been reported in the literature.

PMID- 1984917
TI  - Total hip arthroplasty in ankylosing spondylitis.
AB  - Total hip arthroplasty was performed on 29 hips in 19 patients diagnosed with
      ankylosing spondylitis over a 13-year period. The results were analyzed
      retrospectively with an average follow-up period of more than four years.
      Complete pain relief was achieved in 97%, and significant gains were made in
      ambulatory capacity. The limited gains in total range of motion (average
      improvement 75 degrees) were felt to be primarily due to the high incidence of
      Brooker Class III and IV myositis ossificans (23%) and long-standing soft tissue
      contractures.

PMID- 1984919
TI  - Strength recovery and muscle activation of the knee extensor and flexor muscles
      after arthroscopic meniscectomy. A pilot study.
AB  - Maximal isokinetic strength and electromyographic activity of the operated leg
      were measured preoperatively and one, two, three, and eight weeks postoperatively
      after a partial medial meniscectomy by arthroscopy in a group of ten patients.
      Strength deficits, measured with a Kin-Com dynamometer using a static preloading
      protocol, were found in comparison with a group of matched healthy subjects
      preoperatively and three and eight weeks postoperatively in the knee extensors.
      These deficits were related to previously unreported modifications in the shape
      of the moment-angle curves and a tendency to lower activation levels of the
      vastus medialis (VM) but not the vastus lateralis or rectus femoris muscles. No
      deficits were found in the knee flexors preoperatively or three and eight weeks
      postoperatively, but the medial hamstrings activation level was lower for
      movements at 30 degrees per second. During flexion movements, the percentage of
      coactivation of the antagonist VM was significantly greater than healthy values
      at 30 degrees and 180 degrees per second. These results clearly indicate that
      neuromuscular recovery is not complete when return to work is advocated three to
      four weeks postoperatively. Such findings suggest the need for a rehabilitation
      program to promote recovery of the knee muscles in workers with a physically
      demanding occupation.

PMID- 1984918
TI  - The appearance of the piriformis muscle syndrome in computed tomography and
      magnetic resonance imaging. A case report and review of the literature.
AB  - The piriformis syndrome (PS) is a controversial cause of hip pain because of the
      lack of objective findings to support the diagnosis. Computed tomography (CT) and
      magnetic resonance (MR) imaging revealed PS in a 27-year-old woman. This case may
      be one of the first reports in the literature on a piriformis muscle enlargement
      documented by CT and MR imaging.

PMID- 1984920
TI  - Circulatory dissemination of 15-mu particles from the immature rat femur.
AB  - Venous drainage from the femur of adult animals is not interrupted by occlusion
      of the blood supply in the soft tissue surrounding the diaphysis of the bone.
      Previous studies have shown that the metaphyseal drainage system is capable of
      rapidly transporting particles up to 100 mu in diameter to the lungs. The present
      study was performed to determine if venous drainage from the femur of immature
      animals possesses similar characteristics. Three-week-old rats were given a 5
      microliters intramedullary injection containing radioactively labeled 15-mu
      diameter microspheres. In the intact animal, the particles moved from the
      injection site in the femur to the lungs within two minutes; however,
      obliteration of blood flow in the soft tissue surrounding the femoral diaphysis
      significantly reduced this movement in most animals. The ratio of particles
      moving through the lungs into the peripheral arterial circulation was slow and
      similar to that found in adult animals.

PMID- 1984921
TI  - Range of motion in total knee arthroplasty. A computer analysis.
AB  - A three-dimensional computer model of the knee was formulated based on sectional
      and coordinate data from knee specimens. The model was consistent with published
      data in terms of contact points and ligament length patterns. Prosthetic
      components were designed, and surgical placement was simulated. Maximum flexion
      was limited by tension in the posterior cruciate ligament. Increased dishing of
      the tibial surface reduced flexion, but some dishing was considered necessary for
      reduction of contact stresses. Anteroposterior translation of the tibial
      component had little effect on flexion. Femoral translation had some offset, and
      posterior positioning reduced flexion. The most important surgical variable was
      tibial component tilt in the sagittal plane. Posterior tilt increased motion,
      while anterior tilt decreased motion. The results apply to the choice of total
      knee system, instrument design, and surgical technique.

PMID- 1984922
TI  - Diagnosis of acute rupture of the quadriceps tendon by magnetic resonance
      imaging. A case report.
AB  - Quadriceps tendon rupture occurred in a 56-year-old man receiving anticoagulant
      therapy. The diagnosis was inconclusive until magnetic resonance imaging (MRI)
      was used to delineate the rupture site clearly. MRI is a useful adjunct to
      diagnosis of soft-tissue injuries in cases in which swelling or other soft-tissue
      abnormalities obscure examination or preclude the use of more routine diagnostic
      modalities.

PMID- 1984923
TI  - Long-term results of posterior release surgery for severe flexion contracture of
      the knee in patients with rheumatoid arthritis.
AB  - Twelve knees in nine rheumatoid patients with severe flexion contractures were
      evaluated clinically and roentgenographically for an average of 17.2 years
      (range, six to 25 years) after posterior release surgery. Preoperatively, the
      average extension in the 12 knees was 42.5 degrees, and postoperatively it was
      10.8 degrees. Even though patients were able to walk postoperatively, the
      majority had knee pain when they extended their knees soon after surgery. Seven
      knees required further surgery after correction of the flexion deformity. The
      average time before reconstructive surgery after posterior release was 11.1
      months. In the treatment of severe flexion deformities of the knee in patients
      with rheumatoid arthritis, posterior release surgery was effective only in
      correcting the deformity. Posterior subluxation of the tibia, knee pain, and
      instability occurred soon after surgery. Therefore, patients may require
      additional reconstructive surgery soon after the posterior release.

PMID- 1984924
TI  - A precision guide-pin technique for wedge and rotatory osteotomy of the femur and
      tibia.
AB  - Intraoperative guide-pin placement for the performance of wedge-type and rotatory
      osteotomy of the femur and tibia provides the desired angle of correction from
      single-leg, weight-bearing roentgenograms. A template is used as a guide for pin
      placement. The accuracy of this technique was evaluated by comparing the
      preoperative goal with the correction achieved immediately after surgery and
      after bone healing one year postoperatively. Forty-seven osteotomies, 37 in the
      tibia and ten in the femur, were reviewed. Eighty-five percent of the cases were
      within +/- 3 degrees of the operative goal immediately after surgery, and 81% one
      year postoperatively. Four osteotomies (9%) were considered failures, two because
      of technique and two because of errors in postoperative patient activity level.
      With appropriate preoperative planning, the technique makes accurate osteotomy
      possible in a standard operating room equipped with a C-arm fluoroscope.

PMID- 1984925
TI  - Role of proteoglycan in the provisional calcification of cartilage. A review and
      reinterpretation.
AB  - Study of the calcification of cartilage in endochondral ossification has yielded
      two apparently contradictory views of the role of proteoglycan in this process.
      The ability of proteoglycan to act as a calcium-concentrating agent
      (Kalksalzfanger) in cartilage is consistent with the view that proteoglycans are
      promoters of calcification. However, study of their effect on hydroxyapatite
      formation in vitro suggests that proteoglycans are inhibitors of cartilage
      calcification. A resolution of this paradox is now proposed. Proteoglycans
      inhibit hydroxyapatite formation under in vitro conditions of limited calcium
      availability (in part) by binding calcium ions. However, under in vivo conditions
      of essentially infinite calcium availability, proteoglycans may promote
      hydroxyapatite formation, since binding of calcium to proteoglycan will not
      decrease the free calcium concentration, and the bound calcium may easily be
      displaced. Therefore, it is proposed that the role of proteoglycans in the
      calcification of cartilage is to function as a cation-exchanging calcium
      reservoir.

PMID- 1984926
TI  - Autograft versus allograft for benign lesions in children.
AB  - Benign bone lesions in children are often so large in size that there is not an
      adequate amount of bone available for an autograft to fill the resultant cavity
      after surgical curettage. This study compared autografts and allografts with
      respect to the time required and the success of graft incorporation. Fifty-four
      patients with 61 lesions were studied. Lesions were classified as small volume
      (less than 60 cc) or large volume (more than 60 cc) and were separated into four
      groups: small-volume autograft, large-volume autograft, small-volume allograft,
      and large-volume allograft. Allografts appeared comparable to autografts when
      small-volume lesions were treated. The healing time was slightly longer for
      allografts with an average period of 21 months versus 27 months for autografts.
      Autografts were superior to allografts in rate and completeness of healing for
      solitary large lesions. This increased efficacy presumes a somewhat older child
      in which an adequate amount of bone is available for an autograft. A young child
      with multicentric or polyostotic lesions can still achieve successful
      incorporation with allografts. In this study, 38% healed completely and 29%
      healed partially. Allografts have a distinct place in the treatment of benign
      bone lesions in children.

PMID- 1984927
TI  - Postmortem degradation of demineralized bone matrix osteoinductive potential.
      Effect of time and storage temperature.
AB  - The osteoinductive growth factors present in demineralized bone are degraded by
      tissue enzymes. Storage of rat limbs at low temperature (4 degrees C) before
      harvesting of bones preserves the osteoinductive potential of such factors.
      Storage at room temperature for more than 24 hours causes the recovered bone
      matrix to be biologically inactive, presumably as the result of biodegradation.

PMID- 1984928
TI  - The osteogenic potential of culture-expanded rat marrow mesenchymal cells assayed
      in vivo in calcium phosphate ceramic blocks.
AB  - When whole marrow is introduced into porous calcium phosphate ceramic, bone forms
      on the walls of the pores. As an extension of earlier studies, bone marrow cells
      derived from the femora of inbred rats were introduced into tissue culture, and
      the adherent cells were cultivated, mitotically expanded, subcultured, harvested,
      placed in small cubes of porous calcium phosphate ceramic, and grafted into
      subcutaneous sites of syngeneic rats. Primary marrow-derived, cultured
      mesenchymal cells introduced into ceramic showed strong osteogenic potential,
      with bone forming in the pore regions of ceramic as early as two weeks after in
      vivo implantation; cartilage was observed infrequently in pores that appeared to
      be avascular. Osteogenesis could be observed after the 18th subculture (over 36
      population doublings) when the cells were tested in ceramic at subcutaneous
      sites, whereas chondrogenesis was observed with only the first and second
      subcultured cells in the ceramic delivery vehicle. With increasing numbers of
      subcultures, the initiation of osteogenesis and the apparent rate of bone
      formation declined, and the course of osteogenesis was delayed. Cultured, marrow
      derived mesenchymal cells, even after the 21st subculture (over 40 population
      doublings), exhibited a positive histochemical reaction for alkaline phosphatase.
      However, the in vivo osteogenic potential of these cells was not correlated with
      their alkaline phosphatase activity. The implantation of cell pellets or the
      injection of cell suspensions of fresh or cultured, adherent marrow cells never
      produced bone or cartilage in heterotopic sites. These data indicate that porous
      ceramic provides an excellent delivery vehicle for cells that are capable of
      osteogenic expression and suggest that the composite graft of marrow-derived
      mesenchymal cells and porous ceramic may be useful for repair of massive bone
      defects. It may be possible to culture marrow mesenchymal cells as a source for
      reparative cells for implantation back into autogeneic sites.

PMID- 1984929
TI  - The treatment of malignant tumors by repeated inoculations of erysipelas. With a
      report of ten original cases. 1893.

PMID- 1984930
TI  - Simple bone cysts. The effects of methylprednisolone on synovial cells in
      culture.
AB  - Ten years ago, a protocol using Depo-Medrol injections was developed for the
      treatment of unicameral bone cysts. This concept, designed by tumor surgeons and
      based on theory, has been cautiously approached. However, reproducible results
      have gradually increased clinical acceptance. Understanding the healing process
      has been restricted because of the lack of an experimental model. In an attempt
      to elucidate this mechanism of healing, a cell culture model was used to
      investigate the effects of methylprednisolone on synovial cells. Initially, three
      doses of the drug were tested and maximal changes were noted with the
      concentration of 40 mg/ml. Changes were then quantified by morphology, DNA assay,
      cell protein analysis, and electron microscopy. Results suggest that
      methylprednisolone may have a direct effect on the cellular component of
      unicameral bone cysts.

PMID- 1984932
TI  - Chemotherapy for children with aggressive fibromatosis and Langerhans' cell
      histiocytosis.
AB  - Two disorders involving histologically benign proliferations of fibrous tissue or
      of histiocytes occur preferentially in children and often require combined
      management by an orthopedic surgeon and a pediatric oncologist. Treatment of
      young people with aggressive fibromatosis usually begins with wide local excision
      of the lesion. However, some tumors cannot be completely removed either because
      of their location or because of the risk of subsequent serious dysfunction. Not
      infrequently, local recurrence supervenes despite previous wide local excision,
      and sometimes multiple tumors are present. In these situations a trial of
      multiple-agent chemotherapy incorporating vincristine, actinomycin D, and
      cyclophosphamide may be indicated in an attempt to control the disease. Radiation
      therapy may also be useful, but the relatively high dose (5000 cGy or more)
      needed in a growing child is at times a less attractive alternative. Biopsy of a
      lytic bone lesion in young patients with Langerhans' cell histiocytosis, formerly
      known as histiocytosis X, is also indicated for initial diagnosis. Biopsy and
      curettage are usually curative in the patient with an isolated lesion. Patients
      with multiple simultaneous or recurrent lesions need chemotherapy if dysfunction
      of the liver, spleen, or lungs is present. Drug therapy may also be beneficial
      for children with systemic symptoms. This article outlines suggestions for
      chemotherapeutic treatment in both diseases.

PMID- 1984933
TI  - Limb reconstruction with vascularized fibular grafts after bone tumor resection.
AB  - Limb-salvage operations are being used with increasing frequency for patients
      with malignant bone tumors. For children, when a biologic reconstruction is
      desired, the choice is often between conventional and vascularized fibular
      grafts. An experimental study was performed in dogs to compare the two types of
      fibular grafts for bridging segmental defects in the radius and ulna. Twenty-six
      adult dogs were divided into two groups and studied at intervals of two, three,
      four, six, and 12 months after transplantation. The conventional grafts healed by
      creeping substitution i.e., they were first partially resorbed before new bone
      was laid down. In contrast, the vascularized fibulae maintained their normal
      structure and hypertrophied by subperiosteal new bone formation. The conventional
      fibulae eventually hypertrophied but much later than the vascularized grafts. The
      vascularized grafts were stronger at four and six months. Between six and 12
      months, both grafts remodeled to resemble the size and shape of the forearm bones
      they were replacing. These experimental results have influenced the treatment of
      patients. Vascularized fibular grafts are ideal for diaphyseal defects greater
      than 10 cm long, especially in very young children, a poorly vascularized bed, or
      when bone healing is delayed by chemotherapeutic agents. To maximize hypertrophy,
      an external fixator is used to immobilize the graft rather than a plate, which
      acts as a stress shield.

PMID- 1984931
TI  - Cryosurgery and acrylic cementation as surgical adjuncts in the treatment of
      aggressive (benign) bone tumors. Analysis of 25 patients below the age of 21.
AB  - This article reviews the clinical experience with cryosurgery (use of liquid
      nitrogen) and acrylic cementation (polymethylmethacrylate; PMMA) in the treatment
      of aggressive, benign bone sarcomas and the biologic basis of this technique. The
      results of 25 patients below the age of 21 treated by cryosurgery, with an
      average follow-up period of 60.8 months, are reported. Three approaches to
      surgical reconstruction were used: Group 1 (four patients) had cryosurgery with
      no reconstruction, Group 2 (13 patients) had bone graft reconstruction alone, and
      Group 3 (eight patients) had composite osteosynthesis with internal fixation,
      bone graft, and/or PMMA. The overall control rate was 96% (one recurrence). The
      tumor types were giant-cell tumor, chondroblastoma, aneurysmal bone cyst, and
      malignant giant-cell tumor. Nineteen lesions involved the lower extremity, and
      six lesions were located in the upper extremity. There were two secondary
      fractures (8%), one local flap necrosis, and one synovial fistula. There were no
      infections. Two epiphyseodeses were performed. The functional results were
      excellent (83%), good (13%), and fair (4%). The technique of composite
      osteosynthesis is recommended for all large tumors of the lower extremity.
      Cryosurgical results compare favorably with those obtained by en bloc resection
      and demonstrate the ability of cryosurgery to eradicate tumors while avoiding the
      need for extensive resections and reconstructive procedures.

PMID- 1984934
TI  - Modified Van Nes rotationplasty in the treatment of malignant neoplasms in the
      lower extremities of children.
AB  - A technique of modified Van Nes rotationplasty has been used since 1981 for limb
      salvage surgery in children and adolescents with malignant sarcoma of the lower
      extremity. The original procedure for lesions of the distal femur was further
      modified and adopted for selected lesions of the proximal femur and tibia.
      Sixteen skeletally immature children form the base of this report. The tumors
      were located in the distal femur in ten children, the proximal tibia in five and
      the proximal femur in one. There were no intraoperative complications and
      postoperative complications included one infection requiring debridement and
      three minor healing delays. There were no local recurrences, neurovascular
      compromises, late derotations, or psychologic decompensations. One patient died
      of metastatic disease and another died of a second malignancy (leukemia). The
      remaining patients are good, functional, below-knee prosthesis users who
      participate in a number of sporting and athletic activities. The procedure is
      safe, has a relatively low complication rate, allows for the functional demands
      of an active, growing child, and accommodates for the future growth of
      extremities.

PMID- 1984935
TI  - Ewing's sarcoma. Prognostic factors, disease control, and the reemerging role of
      surgical treatment.
AB  - Advances in the treatment of Ewing's sarcoma have been dramatic. Present
      treatment protocols control local disease by radiotherapy, surgery, or both;
      systemic spread is limited by aggressive multiagent chemotherapy. In patients
      with localized osseous Ewing's sarcoma, five-year survival rates now range from
      54% to an estimated 74%. With late relapse not uncommon, control of the primary
      lesion is critical to long-term survival. Several studies now show improved local
      control and possibly improved survival of patients with surgical treatment of
      primary osseous Ewing's sarcoma.

PMID- 1984936
TI  - Pulmonary metastases and bone sarcomas. Surgical removal of lesions appearing
      after adjuvant chemotherapy.
AB  - Pulmonary metastasis is the leading cause of death in pediatric patients with
      bone tumors. Multiple thoracotomies for surgical removal of individual lesions
      are performed at many centers. To explore the efficacy of this procedure and
      establish guidelines for an appropriate choice of patients, the experience with
      43 thoracotomies in 24 children was reviewed. The appearance of first metastasis
      later than one year after diagnosis, presence of fewer than five nodules, and
      completeness of surgical resection were favorable predictors of postthoractomy
      survival. Early or multiple metastases, unresectable disease, and hilar, nodal,
      or pleural lesions conferred an unfavorable prognosis. With careful patient
      selection, pulmonary metastecotomy is a safe procedure that has few operative or
      long-term complications. It must be emphasized that although surgical removal of
      pulmonary metastases prolongs survival with good quality of life, the majority of
      patients with bone sarcomas ultimately succumb to their disease after
      thoracotomy. Follow-up time of greater than eight years is necessary to
      adequately assess the effectiveness of pulmonary resection in eradicating all
      disease in these patients.

PMID- 1984937
TI  - The effect of chemotherapy on growth in the skeletally immature individual.
AB  - One hundred twenty-two children with nonmetastatic osteogenic or Ewing's sarcoma
      were studied to assess the effect of multiagent adjuvant chemotherapy on skeletal
      growth and final stature. No deviations from the height distributions of a normal
      population were noted at diagnosis. There was a marked retardation of linear
      growth during the year of intensive chemotherapy. Only 15% of the patients grew
      at the expected rate during that year. The distribution of nutritional status
      scores was significantly different at the end of the first year than at baseline.
      The distribution of ultimate height scores was significantly different than the
      baseline distribution. The overall final distribution was also significantly
      different from the normal population expectation. Any absolute difference in
      height, however, is likely to be small. The subgroups that were observed to full
      adult stature showed mean heights of 162 cm for girls and 176 cm for boys.

PMID- 1984938
TI  - What causes cough and wheeze?

PMID- 1984940
TI  - The effects of smoking on the signal-averaged electrocardiogram in normal
      subjects.
AB  - Tobacco smoking increases the risk of sudden cardiac death, possibly by altering
      the substrate for propagation or sustainment of ventricular tachyarrhythmias. To
      test this hypothesis, 15 long-term smokers without known coronary artery disease
      abstained from tobacco smoking for 12 h, after which they underwent SAECG before,
      15 min after and 30 min after smoking two cigarettes. Other than minor
      lengthening of filtered QRS duration, no significant change in time-domain SAECG
      parameters was noted. We conclude that late potentials are not produced by
      cigarette smoking and that ventricular arrhythmia substrate as measured by SAECG
      variables is not worsened in long-term smokers without evidence of coronary
      artery disease.

PMID- 1984939
TI  - Pulmonary surveillance using bronchoscopy and bronchoalveolar lavage during high
      dose antineoplastic therapy.
AB  - Pulmonary failure is a major contributor to morbidity and mortality during marrow
      aplasia following high-dose antineoplastic therapy. For this reason, we initiated
      a pulmonary surveillance program for patients undergoing high-dose chemotherapy
      for leukemia or bone marrow transplantation. As part of this program,
      bronchoscopy with BAL was performed prior to therapy and at the onset of
      granulocytopenia. Thirty-three of the first 57 patients managed in this program
      developed some evidence of pulmonary complications. Twelve patients died in
      aplasia; all had pulmonary failure. Forty patients had clinically significant
      abnormalities on the bronchoscopy before treatment including 12 of 19 patients
      who had normal findings on chest x-ray films, physical examination, and pulmonary
      function testing, and no fever. Twenty-seven patients had clinically significant
      abnormal bronchoscopy or BAL at the onset of granulocytopenia. Thirteen patients
      required additional bronchoscopy. No patient required an open lung biopsy.
      Pulmonary surveillance using bronchoscopy with BAL is useful in the detection of
      pulmonary disease prior to the initiation of and following high-dose
      antineoplastic therapy.

PMID- 1984941
TI  - The chest roentgenogram in pulmonary tuberculosis patients seropositive for human
      immunodeficiency virus type 1.
AB  - To determine the impact that co-infection with HIV has on the radiographic
      presentation of pulmonary tuberculosis, we examined the chest roentgenograms
      obtained before treatment in 225 HIV-tested adult Haitians with bacillary (smear
      or culture or both) positive pulmonary tuberculosis. There were 67 HIV
      seropositive and 158 HIV-seronegative patients. Intrathoracic adenopathy alone
      was more common and parenchymal infiltrates less common in HIV-seropositive
      patients (p less than 0.05). Although a parenchymal infiltrate was less likely to
      be cavitating in the HIV-seropositive group (p less than 0.05) when cavitary
      parenchymal disease was present, HIV seropositivity did not affect the number of
      cavities (single or multiple) or the size of the largest cavity. Patients with
      AIDS were significantly more likely to have a chest radiographic pattern
      consistent with primary tuberculosis (80 percent) than HIV-seropositive patients
      without AIDS (30 percent), and the latter were significantly more likely to have
      such a pattern than HIV-seronegative patients (11 percent) (p less than 0.05).
      The HIV-seropositive patients were equally infectious, regardless of the pattern
      of disease (primary vs postprimary). Even though pulmonary tuberculosis in an HIV
      seropositive adult probably results from reactivation of dormant foci or
      reinfection, the pattern on the chest roentgenogram often suggests primary
      disease, especially if the patient has AIDS.

PMID- 1984942
TI  - Target-flow inspiratory muscle training during pulmonary rehabilitation in
      patients with COPD.
AB  - The effects of additional target-flow inspiratory muscle training (TF-IMT) on the
      performance of the inspiratory muscles, on general exercise capacity, and on
      psychologic parameters during a pulmonary rehabilitation program (PR) were
      studied in 40 patients with COPD selected for ventilatory limitation during
      exercise. The mean age of the patients was 59 years, and the mean FEV1 was
      approximately 50 percent of predicted. All patients participated in a ten-week PR
      program. They were randomized to receive either additional TF-IMT (PR + IMT) or
      not (PR). The TF-IMT was performed by means of a target-flow resistive device;
      the generated mouth pressure and the duration of inspiration and of the
      respiratory cycle were imposed. After the training period, maximal inspiratory
      mouth pressure and EMG-fatigability of the diaphragm were significantly better in
      the PR + IMT group than in the PR group. Maximal work load and psychologic
      symptoms increased to the same extent in both groups. The 12-minute walking
      distance also increased in both groups, but it increased significantly more in
      the PR + IMT group than in the PR group. We believe that additional TF-IMT during
      PR in a selected group of patients with COPD who have ventilatory limitation has
      an extra beneficial effect on the performance of the inspiratory muscles and on
      exercise performance.

PMID- 1984943
TI  - Effects of initial flow rate and breath termination criteria on pressure support
      ventilation.
AB  - To assess whether adjustments in the initial flow rate or breath termination
      criteria affected patient-ventilator synchrony, we studied the ventilatory
      pattern response to PS in 33 patients under two sets of circumstances: during
      seven different levels of delivered initial PS flow and during PS termination at
      50 percent and at 25 percent of peak flow. In the study on initial PS flow, we
      found the following: (a) an optimal initial PS flow could be defined for a given
      level of PS that resulted in the patient obtaining maximal pressure and volume
      from the ventilator; (b) initial PS flows above and below this optimal flow were
      associated with faster breathing frequencies, shorter inspiratory times, smaller
      tidal volumes and a tendency for airway pressure to not reach the selected PS
      level; and (c) optimal initial PS flow was fastest in patients with the lowest
      compliances and the most active ventilatory drives. Changing PS termination
      criteria from 50 to 25 percent of peak flow had minimal effects on the
      ventilatory pattern or synchrony. We conclude that the initial PS flow to achieve
      the selected PS level is important in patient-ventilator synchrony but that
      termination criteria set between 25 and 50 percent of peak flow is not.

PMID- 1984944
TI  - Cardiac rhabdomyoma. Rare cause of fetal death.
AB  - Two cases of nonimmune hydrops fetalis and fetal death associated with cardiac
      rhabdomyoma are reported. Case 1 presented with fetal supraventricular
      tachycardia, and cardiac rhabdomyoma was accurately diagnosed by fetal
      echocardiography. Autopsy revealed multiple rhabdomyomata involving the right
      atrial free wall, the sinoatrial node, and the left ventricle. The left
      circumflex coronary artery was extrinsically compressed by adjacent tumor tissue,
      causing left ventricular myocardial infarction. Case 2 had a unique,
      pedunculated, ball-like rhabdomyoma that almost totally occluded the mitral
      orifice. The causes of fetal death in patients with cardiac rhabdomyoma are
      analyzed and the possibility of fetal surgical management is proposed.

PMID- 1984946
TI  - An outbreak of pneumococcal pneumonia in two men's shelters.
AB  - We report a retrospective study of 39 homeless men hospitalized for acute
      pneumonia from April 1988 to March 1989. All of them had recently stayed in one
      of two shelters. A Streptococcus pneumoniae serotype 1, resistant to
      cotrimoxazole, was isolated in 29 patients (74 percent). Blood cultures were
      positive in 24 (61 percent). The patients were relatively young; none was over 70
      years old. Thirty-five (90 percent) were heavy smokers; 32 (82 percent) were
      alcoholics. The radiologic pattern was atypical in 14 cases (36 percent). The
      only fatal case was linked to the adult respiratory distress syndrome. It is
      likely that the rate of outbreaks of pneumococcal pneumonia is underestimated.
      The homeless are at high risk for pneumococcal pneumonia. In addition, the
      closeness existing in shelters favors the occurrence of outbreaks. Consequently,
      we suggest that shelter residents would benefit from pneumococcal vaccination.

PMID- 1984945
TI  - 99mTc-anti-CEA radioimmunoscintigraphy of lung adenocarcinoma.
AB  - Anti-carcinoembryonic antigen radioimmunoscintigraphy (anti-CEA RIS) in
      colorectal adenocarcinoma has been reported to allow a better estimation of the
      local tumor extension than other radiologic methods. This study evaluated the
      clinical feasibility of a 99mTc-labeled anti-CEA monoclonal antibody (BW 431/26,
      Behring Institute, FRG) in 11 patients for staging of primary adenocarcinoma of
      the lung. The primary tumor size ranged from 3 to 8 cm with a mean of 4 cm.
      Mediastinal and hilar nodes were present in four patients, intrapulmonary
      metastases were present in two patients, and pleural and liver metastases were
      present in one patient each. The CEA levels were in the range of 2 to 265 ng/ml
      and elevated (greater than 5 ng/ml) in six patients. Planar scintigraphy was
      performed at 6 h and 24 h post injection (pi). Analog and digitized images were
      interpreted by two observers. One patient was imaged twice and experienced serum
      sickness due to human anti-mouse antibodies (HAMA) after the second study, which
      showed marked unspecific tracer uptake in liver, spleen, and bone marrow, but no
      specific uptake by the tumor and was excluded from further analysis. Visual
      interpretation identified the primary tumor clearly in seven patients. No tumor
      imaging was observed in two patients. Two patients were classified as having
      questionable imaging due to a poor separation of tumor uptake from mediastinal
      blood pool. The primary tumor could be clearly delineated in both patients after
      comparison with the chest radiograph. Thus, the overall sensitivity for imaging
      of the primary tumor was 82 percent. The average target/background ratio was 1.31
      +/- 0.17:1 at 6 h pi, and 1.30 +/- 0.16:1 at 24 h pi. Hilar and mediastinal nodes
      were correctly suspected in three patients, but the cardiac blood pool hampered a
      clear interpretation. Intrapulmonary and pleural metastases were diagnosed in all
      cases. The single liver metastasis was missed because of the high unspecific
      tracer uptake. Planar anti-CEA RIS with 99mTc BW 431/26 was superior to computed
      tomography (CT) in one case with subtotal tumor resection. We summarize that at
      present, planar anti-CEA RIS with 99mTc BW 431/26 cannot be advised as a routine
      staging procedure in adenocarcinoma of the lung, but it may be helpful in the
      detection of residual or recurrent tumor tissue.

PMID- 1984948
TI  - A qualitative comparison of paper flowsheets vs a computer-based clinical
      information system.
AB  - Demonstrating the value of computerized clinical information systems (CIS)
      relative to its cost has been difficult. Decreased mortality in the intensive
      care unit or a reduction in nursing staff have not been apparent, but CIS does
      lead to a significant improvement in documentation over handwritten flowsheets,
      both in volume and accuracy. This may have a medicolegal and quality assurance
      impact, as well as enhancing patient care.

PMID- 1984947
TI  - Behavior of the pulmonary circulation at rest and during exercise in miliary
      tuberculosis.
AB  - We studied the hemodynamic behavior of the pulmonary circulation at rest and
      during exercise in six patients with MTB. As a group, in contrast to advanced
      fibrocaseous tuberculosis, these patients exhibited normal pulmonary hemodynamics
      at rest and during exercise. Only minor abnormalities in pulmonary vascular
      resistance at exercise (increased PAd-PWP gradient) were noted in two of the
      patients. The increase in Rp during exercise does not appear to be related to
      acute hypoxic vasoconstruction but rather to functional changes (compliance or
      recruitment or both) of the pulmonary microvasculature. In the genesis of these
      functional changes, chronic alveolar hypoxia and the inflammatory-fibrotic
      process might be interacting.

PMID- 1984949
TI  - Combined thermodilution and two-dimensional echocardiographic evaluation of right
      ventricular function during respiratory support with PEEP.
AB  - In ten patients requiring respiratory support for an episode of acute respiratory
      failure (ARF), the best therapeutic level of PEEP was determined by measurement
      of changes in lung and chest wall compliance (CT) during a PEEP challenge from 0
      to 20 cm H2O. During this challenge, hemodynamic monitoring combined with
      thermodilution measurement of right ventricular (RV) ejection fraction (EF) and
      two-dimensional echocardiographic measurement of RV size permitted assessment of
      the effects of increasing levels of PEEP on RV function. RV preload, as reflected
      by RV end-diastolic volume (EDV) and two-dimensional RV end-diastolic area (EDA),
      remained unchanged and RV diastolic compliance progressively decreased. On the
      other hand, RV systolic function, as assessed by RVEF and two-dimensional RV
      fractional area contraction (FAC), was progressively depressed. Substantial
      deleterious effects of PEEP were noted at high levels of PEEP including reduced
      CT and augmented pulmonary vascular resistance. Inadequate increase in RV preload
      to compensate for increased RV afterload resulted in depressed RV systolic
      function and contributed to the reduction in cardiac output. Finally, two
      dimensional echocardiography proved to be more sensitive than fast-response
      thermodilution to evaluate change in RV function.

PMID- 1984950
TI  - Endotoxemia in human septic shock.
AB  - To evaluate the incidence, pattern and clinical importance of endotoxemia in
      septic shock, frequent, serial endotoxin determinations were made prospectively
      in patients with shock. Detectable endotoxin occurred in 43 of 100 patients with
      septic shock, but in only one of ten patients with shock due to nonseptic causes.
      During septic shock, endotoxemia frequently occurred in the absence of Gram
      negative bacteremia. Using a logistic regression model, multiple organ failure
      occurred 10.3 times more frequently and depression of left ventricular ejection
      fraction (less than or equal to 45 percent) 4.8 times more frequently in
      endotoxemic patients. In patients with positive blood cultures, endotoxemia was
      associated with a high mortality. We conclude that endotoxemia occurs frequently
      in septic shock and is associated with severe manifestations of this syndrome,
      including cardiac depression and multiple organ failure. This study suggests that
      endotoxin is an important mediator of septic shock and supports efforts to
      develop anti-endotoxin therapies for treating patients with this disease.

PMID- 1984951
TI  - Respiratory failure and death following acute inhalation of mercury vapor. A
      clinical and histologic perspective.
AB  - A family of four was exposed to toxic levels of mercury vapor while attempting to
      extract silver from mercury amalgam. All four suffered respiratory failure and
      subsequent death despite chelation therapy with dimercaprol. Histologic findings
      at autopsy were similar in all four cases demonstrating a progression of acute
      lung injury that appeared related to postexposure day survival. There were no
      clinical signs of extrapulmonary manifestations despite toxic serum mercury
      levels. Although serum mercury levels decreased in response to the mercury
      chelating agent dimercaprol, serum levels remained in the toxic range and no
      clinical response was observed. Acute inhalational exposure to high
      concentrations of mercury vapor causes pneumonitis that can lead to respiratory
      failure and death. This continues to be a health hazard in both the workplace and
      the home environment.

PMID- 1984952
TI  - New developments in asbestos-induced pleural disease.

PMID- 1984953
TI  - The hyperventilation challenge test. Another means of identifying coronary
      vasospasm in patients with angina-like chest pain.

PMID- 1984954
TI  - Pneumococcal pneumonia. Predispositions and prevention.

PMID- 1984956
TI  - Sudden superior mediastinal enlargement.

PMID- 1984955
TI  - A longitudinal study of respiratory symptoms in a community population sample.
      Correlations with smoking, allergen skin-test reactivity, and serum IgE.
AB  - Chronic cough and/or phlegm, wheeze in the absence of colds, and rhinitis
      attributed to allergies are three of the most common respiratory symptoms
      encountered in community populations. In this study, we have determined the
      prevalence of these complaints in a random population sample (n = 1,109) using
      standardized questionnaires at two points in time, eight years apart. Cross
      sectional prevalence and changes in symptom occurrence have been correlated with
      smoking status, allergen skin test reactivity, and total serum IgE levels. Our
      objective was to determine the individual and combined influence of these three
      variables on symptom prevalence. Initially, 19.2 percent of the population
      admitted to wheeze, 17.9 percent to cough, and 44.1 percent to allergic rhinitis.
      Cough and wheeze prevalence changed little over the eight-year period, while
      rhinitis increased 11 percent by the second survey. The occurrence of chronic
      cough was strongly correlated with smoking, and was not further influenced by
      either allergen skin reactivity or IgE level. Conversely, rhinitis prevalence was
      related to skin test reactivity with no additional association with smoking or
      IgE level. The occurrence of wheeze in the absence of colds was associated with
      both smoking and allergen skin reactivity. Among smokers, the prevalence was over
      30 percent and was similar in both skin test positive (STP) and skin test
      negative (STN) individuals. However, on both surveys, STP ex-smokers and
      nonsmokers had significantly more wheeze than those who were STN. While the
      prevalence of wheeze in STN nonsmokers was low (6.8 percent), an IgE-wheeze
      relationship was also suggested on the second survey. In addition to these cross
      sectional symptom relationships, changes in either smoking status or allergen
      skin reactivity during the study period were associated with changes in the
      prevalence of each symptom.

PMID- 1984958
TI  - Psychosocial issues in lung cancer patients (Part 1).

PMID- 1984959
TI  - Rabbit skeletal muscle PO2 during hypodynamic sepsis.
AB  - We measured skeletal muscle tissue PO2 (PtO2) in anesthetized rabbits (n = 7)
      following infusion of an intravenous bolus of E coli endotoxin. An array of
      surface PO2 microelectrodes was placed over the hindlimb biceps femoris muscle
      and sufficient readings were obtained to construct a PtO2 histogram. Changes in
      the histogram standard deviation were used to characterize micro-circulatory
      maldistribution. Systemic O2 consumption (VO2) was measured by the expired gas
      method. Cardiac output (Q) and systemic O2 transport (TO2) were calculated.
      Samples of arterial, right atrial (ra), and hindlimb venous blood, from a
      catheter placed in the infrarenal portion of the vena cava, were simultaneously
      obtained for measurement of blood gases and saturations. Following the
      administration of endotoxin, there were decreases in Q and TO2 of approximately
      50 percent. The VO2 initially decreased 23 percent, but returned to baseline
      levels 30 minutes after endotoxin administration. Systemic O2 extraction ratio
      (ERO2 = VO2/TO2) increased from 0.32 +/- .03 to 0.54 +/- .07 (p less than 0.01),
      whereas hindlimb ERO2 increased from 0.42 +/- .03 to 0.60 +/- .02 (p less than
      0.01). The arithmetic mean of the PtO2 histograms decreased after endotoxin
      infusion (43 +/- 4 to 7 +/- 2 mm Hg; p less than 0.01), but PLO2 remained at
      baseline levels (35 +/- 2 vs. 33 +/- 2 mm Hg; p = NS). The standard deviation of
      the PtO2 histograms remained constant during the experiment. This finding
      supports the notion that skeletal muscle microcirculatory heterogeneity does not
      increase during endotoxin induced hypodynamic sepsis.

PMID- 1984960
TI  - Natural killer cell activity in a rat model of amiodarone-induced interstitial
      lung disease.
AB  - The role of lymphocytes in the pathogenesis of amiodarone-induced lung disease is
      controversial. Increases in the percentages of lymphocytes in bronchoalveolar
      fluid of both patients and animals with amiodarone pulmonary toxicity have been
      reported. To assess whether these lymphocytes are functionally activated, we
      measured natural killer cell activity in the lungs and blood of rats with
      amiodarone-induced pulmonary toxicity. Amiodarone treated rats exhibited
      pathologic evidence of amiodarone-induced lung disease after one week of
      treatment and this injury was sustained and more extensive during the remainder
      of the study period. Control rats had histologically normal lungs. Blood NK
      activity was equally present in both amiodarone-treated and control groups and
      was not significantly different over the course of the study (16 +/- 3 percent
      and 13 +/- 2 percent, respectively; p greater than 0.05). Thus, NK cells were
      activated only in the lungs of rats treated with amiodarone, suggesting a local
      immune response in the lung. These data support the concept that lymphocytes play
      an important role in the pathogenesis of amiodarone-induced lung disease.

PMID- 1984957
TI  - Imaging techniques in the evaluation of tracheobronchial neoplasms.

PMID- 1984962
TI  - Pulmonary reactions caused by welding-induced decomposed trichloroethylene.
AB  - This is the report of a welder who performed argon-shielded electric arc welding
      in an atmosphere containing trichloroethylene. He developed immediate respiratory
      symptoms, pulmonary edema 12 hours after exposure, and recurring dyspnea ten days
      after exposure. These pulmonary reactions might be explained by inhalation of
      decomposition products of trichloroethylene such as dichloroacetyl chloride and
      phosgene.

PMID- 1984961
TI  - Minute squamous cell carcinoma arising in the wall of a congenital lung cyst.
AB  - A case of minute squamous cell carcinoma arising in a congenital lung cyst is
      reported. Two aspects of this case were notable. First, we were able to make the
      diagnosis of squamous cell carcinoma by bronchial lavage at an early stage.
      Second, to our knowledge, this is the first case of probable de novo origin of
      squamous cell carcinoma in a congenital lung cyst.

PMID- 1984963
TI  - Renal vein thrombosis. Initial manifestation of Goodpasture's syndrome.
AB  - We report a patient who presented with renal vein thrombosis and nephrosis that
      progressed to alveolar hemorrhage and renal failure. Renal biopsy
      immunofluorescence and serum antiglomerular basement membrane antibody titer
      studies confirmed the diagnosis of Goodpasture's syndrome. To our knowledge, this
      is the first report of renal vein thrombosis as the initial presentation of
      Goodpasture's syndrome.

PMID- 1984964
TI  - Lightning injury with lung bleeding in a tracheotomized patient.
AB  - A 68-year-old man, who had undergone laryngectomy six months earlier, was struck
      by lightning and developed pulmonary hemorrhage. This was attributed to pulmonary
      barotrauma due to a lightning blast via his tracheostoma.

PMID- 1984965
TI  - Di George anomaly with atrioventricular canal.
AB  - We report the first case of Di George anomaly associated with atrioventricular
      canal. This combination of anomalies may represent a chance occurrence of two
      situations happening in the same patient or, alternatively, the result of a
      single unknown embriogenetic mechanism.

PMID- 1984966
TI  - Obliterative bronchiolitis: virus induced?
AB  - This report describes a 28-year-old patient with an acute onset of respiratory
      symptoms associated with clinical and roentgenographic features of an
      interstitial lung disease which proved fatal. The entity of bronchiolitis
      obliterans, which was diagnosed on transbronchial biopsy, is discussed, with
      particular emphasis on the postinfectious type.

PMID- 1984968
TI  - Magnetic resonance imaging--the evaluation of choice in residual shunt after
      congenital heart disease surgery?
AB  - Accurate anatomic diagnosis presents a dilemma in patients with residual shunt
      after corrective surgery for congenital heart disease. We describe a patient who,
      after atrial septal defect repair, developed dyspnea and central cyanosis despite
      normal pulmonary arterial pressures and right heart chamber size. A role for
      early MRI is suggested.

PMID- 1984967
TI  - Tension pneumothorax secondary to a gastropleural fistula in a traumatic
      diaphragmatic hernia.
AB  - We report a case of tension pneumothorax due to a gastropleural fistula resulting
      from perforation of the stomach in a traumatic diaphragmatic hernia. Awareness of
      perforation of strangulated stomach or bowel in a diaphragmatic hernia as a cause
      of pneumothorax, with or without tension physiology, in a patient with a history
      of trauma is important so that surgical repair can be undertaken without delay.

PMID- 1984971
TI  - Aortic dissection presenting as upper airway obstruction.

PMID- 1984969
TI  - Pneumocystis carinii pneumonia. Rare cause of hemoptysis.
AB  - Pneumocystis carinii pneumonia is a frequent manifestation of the acquired
      immunodeficiency syndrome (AIDS). It commonly presents with nonproductive cough,
      fever, and dyspnea. We report this case of P carinii pneumonia presenting with
      hemoptysis, since to the best of our knowledge, hemoptysis has not been reported
      to be a presenting manifestation of P carinii pneumonia. Autopsy revealed
      multiple lung cavities.

PMID- 1984970
TI  - Nonsurgical treatment of Histoplasma endocarditis involving a bioprosthetic
      valve.
AB  - Endocardial involvement associated with disseminated histoplasmosis has been
      infrequently documented, especially among patients with prosthetic valves. The
      therapeutic approach to these patients is also not yet clearly defined. A 54-year
      old man with prosthetic valve endocarditis due to histoplasmosis was successfully
      treated with amphotericin B. A review of the literature suggests that the optimal
      form of therapy is likely a combination of surgical replacement of the involved
      valve and high dose amphotericin B. Successful therapy with amphotericin B alone
      may, however, be achieved if surgery is not a viable option.

PMID- 1984973
TI  - Cost comparison of care for chronic ventilator patients.

PMID- 1984974
TI  - Economic costs of spontaneous pneumothorax.

PMID- 1984972
TI  - Noncardiogenic pulmonary edema complicating massive diltiazem overdose.
AB  - Non-cardiogenic pulmonary edema has not been previously described in calcium
      channel blocker overdose. We describe a case of non-cardiogenic pulmonary edema
      occurring during the course of therapy for massive diltiazem overdose in a young
      patient with anorexia nervosa. Review of the current literature suggests that
      major and minor pulmonary complications occur with some frequency in the setting
      of calcium channel blocker overdose although their exact incidence remains
      unclear.

PMID- 1984975
TI  - Early description of ARDS.

PMID- 1984976
TI  - Chlorinated solvents, welding and pulmonary edema.

PMID- 1984977
TI  - How long do patients with cor pulmonale secondary to pulmonary fibrosis survive?

PMID- 1984978
TI  - Bronchial asthma.

PMID- 1984980
TI  - Safety and efficacy of thrombolytic therapy for superior vena caval syndrome.

PMID- 1984979
TI  - Cough in hot pepper workers.
AB  - STUDY OBJECTIVE: To determine whether there is an effect on the prevalence of
      respiratory symptoms, an alteration in lung function, or an increase in the cough
      threshold to capsaicin among workers chronically exposed to hot chili (Capsicum)
      peppers. DESIGN: Cross-sectional study of responses to a structured
      questionnaire, lung function assessed by spirometry and cough threshold to
      inhalation of capsaicin aerosol in a group of occupationally-exposed Capsicum
      workers as compared to non-exposed employees of the same work site. SETTING:
      Spice manufacturing facility. PARTICIPANTS: Twenty-two Capsicum-exposed and 19
      nonexposed workers. MEASUREMENTS AND MAIN RESULTS: When evaluated by
      questionnaire, 13 (59 percent) of the Capsicum-exposed workers reported cough as
      compared to 4 (21 percent) of the nonexposed workers (p less than 0.05). Baseline
      FEV1 and FVC did not differ between the two groups. Cough threshold, as assessed
      by the lowest concentration of inhaled capsaicin eliciting cough, was related to
      workplace exposure (p = 0.05), displaying a bimodal pattern of higher and lower
      cough thresholds among the Capsicum workers as compared to a unimodal
      distribution among the nonexposed workers. Within the exposed group, a higher
      cough threshold was significantly related to male gender (p = 0.03) and was
      associated to a lesser extent with dietary preference for hot food (p = 0.09) and
      cumulative cigarette smoking (p = 0.07). CONCLUSION: Chronic occupational
      exposure to chili peppers is associated with complaints of cough but does not
      alone lead to decreased responsiveness of capsaicin-sensitive nerves when
      assessed by cough threshold. The cough response to capsaicin inhalation may be
      modified by the effects of multiple, potentially interactive factors.

PMID- 1984981
TI  - Fiberoptic bronchoscopy for refractory cough.
AB  - Fiberoptic bronchoscopy (FB) has a low yield in the diagnosis of chronic cough
      (greater than 3 weeks) in unselected patients. We assessed the yield of FB for
      cough during a four-year period in patients with nonlocalizing chest
      roentgenograms who were refractory to diagnostic efforts and empiric
      bronchodilator or antitussive therapy. Seven (28 percent) of 25 patients
      undergoing FB for cough (of greater than 1,500 bronchoscopies) had diagnostic
      findings (broncholithiasis, two; tracheobronchopathia osteochondroplastica, two;
      and tuberculous bronchostenosis, laryngeal dyskinesia, and arytenoid polyp, one
      each). No tracheobronchial neoplasms were detected. Age greater than 50 years and
      female sex independently predicted positive results (p = 0.02 Fisher's exact
      test), while duration of cough (two to 240 months), airflow, and smoking status
      did not. When patients with prior pulmonary or extrathoracic neoplasms were
      excluded, seven (35 percent) of 20 studies were diagnostic. Diagnoses potentially
      could have been made by thoracic computed tomographic scanning in four patients
      and indirect laryngoscopy in two. Fiberoptic bronchoscopy has a respectable yield
      for diagnosis of refractory chronic cough and is a reasonable procedure in
      carefully selected patients.

PMID- 1984982
TI  - Angiotensin-converting enzyme inhibitors and cough. Prevalence in an outpatient
      medical clinic population.
AB  - To determine the frequency of ACE inhibitor cough in an outpatient medical clinic
      population, a cross-sectional epidemiologic survey using mailed questionnaires
      was done. Patients were randomly selected from a computerized hospital pharmacy
      data base. The overall prevalence of cough was 19 percent in the ACE inhibitor
      groups compared with 9 percent in the hydrochlorothiazide-treated group. The
      observed odds ratio for cough among ACE inhibitor users was 2.3 (95 percent CI,
      1.02 to 5.00). This study is the first systematic investigation of frequency and
      characteristics of ACE inhibitor cough that includes a control group. Our results
      suggest that cough may more frequently accompany treatment with ACE inhibitors
      than has been previously reported. We recommend that physicians specifically
      inquire about cough in patients taking an ACE inhibitor. Recognition of this side
      effect may prevent unnecessary testing and treatment of patients receiving ACE
      inhibitors.

PMID- 1984983
TI  - Intermediate care units. Graded care options.

PMID- 1984984
TI  - Snoring (I). Daytime sleepiness in regular heavy snorers.
AB  - Fifteen men, mean (means) age 44 years, were investigated. Their means body mass
      index was 21.9 kg/m2, and all of them had a respiratory disturbance index below 5
      and had good nocturnal oxygen saturation. The subjects were monitored several
      nights both with and without the following devices: a tight-fitting facial mask,
      a pneumotachometer, and an esophageal balloon. They were also monitored with and
      without nasal continuous positive airway pressure. The Multiple Sleep Latency
      Test was administered after three of the experimental nights (after the baseline
      nights and after the second nasal CPAP night). Determination of short EEG
      arousals during nocturnal sleep, which lasted 2 to 10 s, was performed. The
      relationship between short EEG arousals, the esophageal pressure nadir, and
      airflow decrease was investigated. We also determined the relationship between
      clinical reporting of decrease in daytime alertness and MSLT results, and the
      relationship between MSLT results and the frequency of EEG arousals. The
      monitoring indicated that heavy snorers may present significant increase in Pes
      nadir with abrupt decrease in flow leading to EEG arousals. The frequency at
      which EEG arousals occur has an impact on MSLT scores. Nasal CPAP improves MSLT
      scores and eliminates these respiration-related EEG arousals. Some heavy snorers
      without obstructive sleep apnea syndrome may be at risk of having a decrease in
      daytime alertness.

PMID- 1984985
TI  - Pharyngeal volume in asymptomatic snorers compared with nonsnoring volunteers.
AB  - STUDY OBJECTIVE: to determine if asymptomatic snorers have smaller pharyngeal
      volumes than age- and height-matched nonsnorers. DESIGN: we recruited
      asymptomatic heavy snorers and nonsnorers for a study. Each snorer was matched by
      age (+/- 3 years) and height (+/- 2 inches) with a nonsnorer. The nonsnorers were
      required to be near ideal body weight. All volunteers underwent overnight
      polysomnography, pulmonary function testing, and magnetic resonance imaging of
      the pharynx while awake. The volume of the pharynx was determined by a computer
      with data input from a digitizing instrument. SETTING: Veterans Administration
      Hospital and University of Florida Teaching Hospital PARTICIPANTS: Nine
      volunteers were recruited for both the snorer and nonsnorer groups. Each
      participant was paid $50. There were no interventions. MEASUREMENTS AND RESULTS:
      There were no differences in sleep variables between the two groups. There was
      also no significant difference between pharyngeal volumes for the two groups.
      CONCLUSIONS: The volume of the pharynx in asymptomatic snorers is similar to the
      volume in age- and height-matched nonsnorers.

PMID- 1984986
TI  - Safety and efficacy of thrombolytic therapy for superior vena cava syndrome.
AB  - The experience at the Cleveland Clinic from 1982 to 1990 using thrombolytic
      therapy for superior vena cava (SVC) syndrome was retrospectively reviewed.
      Sixteen patients, 11 of whom had indwelling central venous catheters, were
      treated with either urokinase (n = 11) or streptokinase (n = 5). Either urokinase
      (4,400 U/kg bolus followed by 4,400 U/kg/h) or streptokinase (250,000 U bolus
      followed by 100,000 U/h) was used, and venograms were performed before and after.
      Overall, 56 percent of patients had complete clot lysis and relief of symptoms.
      Thrombolytic therapy was effective in eight (73 percent) of 11 patients receiving
      urokinase and one (20 percent) of five patients receiving streptokinase. Of those
      with a central venous catheter, eight (73 percent) of 11 patients were
      successfully lysed, whereas only one (20 percent) of five patients was
      successfully lysed if no catheter was present. If thrombolytic therapy was
      performed less than or equal to five days of symptom onset, seven (88 percent) of
      eight patients were successful, if thrombolytic therapy was performed greater
      than five days after symptom onset, two (25 percent) of eight patients were
      successful. Symptoms were relieved and the catheter was preserved in patients in
      whom thrombolytic therapy was effective. Factors predicting success were as
      follows: (1) the use of urokinase compared with streptokinase; (2) the presence
      of a central venous catheter; and (3) a duration of symptoms less than or equal
      to five days.

PMID- 1984987
TI  - The challenge of pulmonary hypertension.

PMID- 1984988
TI  - Comparison of incentive spirometry and intermittent positive pressure breathing
      after coronary artery bypass graft.
AB  - Fifty-two patients were randomized to receive either incentive spirometry (IS) or
      intermittent positive pressure breathing (IPPB) in addition to conventional chest
      physical therapy following coronary artery bypass grafting. Slow vital capacity
      and peak expiratory flow readings decreased rapidly and to an equal extent in
      both groups after surgery, and partly recovered by the sixth postoperative day
      (POP). Arterial PO2 values were similar for the groups on the first three POPs.
      On the POPs 2, 3, and 6, the number of chest films showing atelectases as well as
      the number of individual patients having atelectases revealed no statistically
      significant differences between the two groups. Based on the three variables
      studied, we consider both devices equal in efficiency after coronary surgery.

PMID- 1984989
TI  - Metered dose inhalers for bronchodilator delivery in intubated, mechanically
      ventilated patients.
AB  - We determined the relative efficacy of two bronchodilator aerosol delivery
      methods in 18 intubated mechanically ventilated patients with airways
      obstruction. Two treatment arms, consisting of albuterol 270 micrograms (three
      puffs) from a metered dose inhaler and albuterol 2.5 mg from a saline solution
      nebulized with an updraft inhaler, were compared in a single blind, randomized
      crossover design. Pulmonary function was evaluated using an interrupter
      technique. Changes in passive expiratory flow at respiratory system recoil
      pressures between 6 and 10 cm H2O provided the therapeutic endpoints. Paired
      measurements were made before and 30 minutes after drug delivery. The MDI and NEB
      resulted in similar improvements in iso-recoil flow (mean increase for both
      groups = 0.1 L/s). Treatment sequence, severity of obstruction, and
      bronchodilator responsiveness had no effect on relative efficacy. Albuterol
      caused a small but significant increase in heart rate that was similar following
      both delivery methods. We conclude that bronchodilator aerosol delivery with
      metered dose inhalers provides a viable alternative to nebulizer therapy in
      intubated mechanically ventilated patients and may result in a cost savings to
      hospitals and patients.

PMID- 1984991
TI  - Longitudinal study of near fatal asthma.
AB  - The effect of careful follow-up and treatment modification for 45 patients with
      an admission for NFA has been studied. In 24 of 45, inciting events were
      recognized. BDP was used by 14 patients pre-NFA. In the mean follow-up of 863
      days, there have been no deaths and seven patients have been readmitted with
      asthma. Six of the 45 patients have attained normal FEV1 and PC20H. Blunted
      perception of breathlessness, change in VAS ratio/change in FEV1, was found when
      first measured, but normalized to be no different than that of other asthmatic
      subjects as airway responsiveness became milder. The CO2 ventilatory responses
      did not differentiate individual NFA patients from non-NFA asthmatic or normal
      subjects. Comparison of the NFA cohort with the 1985 asthma admission cohort
      showed that an asthma admission within the last five years was a risk factor for
      a NFA episode.

PMID- 1984992
TI  - Acute eosinophilic pulmonary disease associated with the ingestion of L
      tryptophan-containing products.
AB  - A series of four patients with pulmonary infiltrates, pleural effusions,
      hypoxemia, peripheral eosinophilia, and symptoms of dyspnea, fatigue, and
      weakness is reported. Lung tissue obtained in three patients revealed
      interstitial pneumonitis, small-to-medium-vessel mixed-cell vasculitis, and
      alveolar exudate of histiocytes and eosinophils. All patients reported ingestion
      of L-tryptophan-containing products at a time when an association between L
      tryptophan and the eosinophilia-myalgia syndrome was established. This clinical
      pattern of pulmonary involvement may be part of the continuum of the eosinophilia
      myalgia syndrome. The pathophysiology of this syndrome and the relationship with
      the ingestion of L-tryptophan-containing products have not yet been identified.

PMID- 1984990
TI  - Complications of general anesthesia for Nd:YAG laser resection of endobronchial
      tumors.
AB  - We studied the incidence and mechanisms of cardiovascular complications and
      postoperative respiratory insufficiency associated with GA and Nd:YAG laser
      endobronchial tumor resection. The records of 73 patients undergoing 87
      procedures were reviewed. Preoperative status, anesthetic methods and
      perioperative complications were analyzed by multiple regression to determine
      predictors of outcome. Twenty-three percent of patients had greater than 90
      percent mainstem bronchus obstruction. Longer serum elimination half-life of
      relaxant drug was significantly correlated with longer duration of mechanical
      ventilation after neuromuscular blockade reversal. Cardiovascular complications
      were noted in 24 procedures and often required therapeutic intervention.
      Variables predicting cardiovascular complications included longer duration of GA
      and increasing age. Perioperative respiratory and cardiovascular complications
      are common after GA for Nd: YAG laser resection. Short-acting neuromuscular
      relaxants, careful assessment prior to postoperative extubation, limiting
      duration of GA and cardiovascular monitoring are recommended when implementing GA
      for Nd: YAG laser resection of endobronchial tumors.

PMID- 1984993
TI  - The diagnostic utility of the antibody-coated bacteria test in intubated
      patients.
AB  - PURPOSE: Pilot study to determine if the presence of antibody-coated bacteria
      (ACB) in sputum specimens obtained from endotracheal tube suctioning would aid in
      the diagnosis of lower respiratory tract infection (LRTI). PATIENTS AND METHODS:
      All endotracheally intubated and mechanically ventilated patients for a two-month
      period were recruited for study. The diagnosis of LRTI was based on a clinical
      suspicion sufficient enough to start or change antibiotic therapy. Specimens were
      obtained by blind endotracheal tube suctioning. After processing, sputum smears
      were stained with fluorescein-labelled antibody to the Fc portion of IgG, IgM,
      and IgA. More than five fluorescein-labelled bacteria per oil immersion field
      were considered positive smears. RESULTS: Seventy-one specimens were obtained
      from 36 patients. Eighteen specimens were positive in 12 patients, all of whom
      had LRTI. No specimen was positive in patients not diagnosed as having LRTI. The
      ACB test was positive in 12 of 25 patients with LRTI. Patients with LRTI but
      negative ACB were more likely to have received prior antibiotic therapy (p less
      than 0.001). ACB was positive prior to the clinical diagnosis of LRTI in seven of
      nine patients (av 4.1 days, range 2-6 days) and converted to negative in three
      specimens obtained seven or more days after starting appropriate antibiotics,
      while in three specimens it remained positive three-six days post treatment
      initiation. CONCLUSIONS: The ACB test appears to be highly specific for the
      presence of LRTI in intubated patients. Sensitivity of the test may be adversely
      affected by prior antibiotic therapy. A positive ACB test may predict the
      subsequent development of LRTI. Further study is warranted.

PMID- 1984994
TI  - Diagnosis of Campylobacter pylori gastritis.
AB  - Campylobacter pylori is a bacterium that inhabits gastric mucosa. It causes
      chronic active gastritis and is highly associated with duodenal ulcer.
      Campylobacter pylori has a urease enzyme (not present in man), which allows
      diagnosis by a [14C]urea breath test. We compared two noninvasive tests, the
      breath test and serum ELISA, to biopsy and histologic diagnosis. Twenty-two
      patients who underwent gastroduodenoscopy for evaluation of possible peptic ulcer
      disease entered the study. The breath test detected the organism in eight of
      eight patients biopsy-positive for the organism (sensitivity 100%). The breath
      test was negative in 12 of the 14 patients who were biopsy-negative (specificity
      86%). The ELISA was performed in 14 patients. It was positive in 5 of 5 patients
      biopsy-positive for the organism (sensitivity 100%) and negative in 7 of 9
      patients who were biopsy-negative (specificity 78%). We conclude that both the
      ELISA and the [14C]urea breath test are excellent noninvasive methods to detect
      Campylobacter pylori. However, only the breath test is suitable for following the
      response to treatment, as it detects the presence of the organism rather than an
      immune response to it.

PMID- 1984995
TI  - Zollinger-Ellison syndrome. Relation to Helicobacter pylori-associated chronic
      gastritis and gastric acid secretion.
AB  - Since Helicobacter pylori infects the gastric mucosa in most patients with
      chronic duodenal ulcer, infection with this organism has been implicated in the
      pathogenesis of this common disease. We postulated that if H. pylori is
      pathogenic in the usual type of duodenal ulcer, it should be less common when
      duodenal ulcer has another, specific etiology, such as Zollinger-Ellison
      syndrome. Gastric mucosa was compared from 18 patients with proven Zollinger
      Ellison syndrome (17 of whom had had duodenal ulcer disease) and 18 controls with
      chronic duodenal ulcer without such a diagnosis. All subjects, who were matched
      for age and sex, had undergone elective gastric resections. Gastric tissues were
      stained by hematoxylin-eosin and Giemsa and were reviewed by an experienced
      pathologist who was unaware of the diagnosis. The frequency of H. pylori in
      patients with Zollinger-Ellison syndrome (8/18) was lower than in controls with
      duodenal ulcer (16/18; P less than 0.02). Moreover, chronic antral gastritis
      scores were higher in patients with duodenal ulcer (P less than 0.01). In
      Zollinger-Ellison syndrome, peak acid output was lower in patients positive
      (median 22 meq/30 min) compared to those negative for H. pylori (median 32 meq/30
      min; P less than 0.02) but serum gastrin was correspondingly lower in patients
      positive for H. pylori (P less than 0.05). H. pylori infection appears to be more
      frequent when duodenal ulceration is not associated with another etiology, such
      as acid hypersecretion in Zollinger-Ellison syndrome. H. pylori infection in
      Zollinger-Ellison syndrome may also be associated with decreased gastric acid
      secretion.

PMID- 1984996
TI  - Abdominal tuberculosis--a cause of portal vein thrombosis and portal
      hypertension.

PMID- 1984997
TI  - IL-6 and TNF alpha in ascitic fluid during spontaneous bacterial peritonitis.

PMID- 1984999
TI  - Peptic ulcer perforation as the presentation of Zollinger-Ellison syndrome.
AB  - We examined the characteristics of patients with Zollinger-Ellison syndrome who
      developed a perforation prior to diagnosis to determine whether any clinical
      features were useful markers of the syndrome. Of 160 patients with Zollinger
      Ellison syndrome, perforation occurred prior to the diagnosis being made in 11
      (7%). At surgery, perforations were found in the duodenum in six cases and in the
      jejunum in five. In no case was tumor identified at emergency surgery, and the
      diagnosis of Zollinger-Ellison syndrome was made only in the postoperative period
      when excessive gastric secretions were noted. Neither acid output nor serum
      gastrin concentration were useful predictors for perforation. The patients, six
      men and five women, were 27-61 years old (median 48) and one had MEN-1. Three
      patients had no symptoms prior to the perforation. The other eight had symptoms
      for 1-15 years, with diarrhea occurring in 45% of the cases. Following the
      diagnosis of Zollinger-Ellison syndrome, patients were given medication to
      control gastric acid hypersecretion. Eight patients remained well, but the three
      patients who had had a partial gastrectomy had a complicated course despite
      medical therapy. Although features of perforation in Zollinger-Ellison syndrome
      are not specific, jejunal perforation or perforation associated with a history of
      diarrhea is suggestive of the diagnosis. Serum gastrin should be measured in
      every case and a partial gastrectomy avoided.

PMID- 1984998
TI  - Helicobacter pylori and Zollinger-Ellison syndrome.
AB  - Helicobacter pylori (previously Campylobacter pylori) is almost invariably
      associated with chronic duodenal ulcer disease. The relationship between H.
      pylori infection and duodenal ulcer in Zollinger-Ellison syndrome is unknown. We
      investigated the frequency of H. pylori infection in Zollinger-Ellison syndrome
      and also what effect H. pylori infection had on gastric function in patients with
      Zollinger-Ellison syndrome. H. pylori infection was diagnosed based on a specific
      serologic (ELISA) assay based on high-molecular-weight cell-associated proteins
      of H. pylori. We studied 20 patients with Zollinger-Ellison syndrome; 15 men and
      5 women ranging in age from 24 to 71 years, median age 51. Six Zollinger-Ellison
      syndrome patients had H. pylori infection compared to 100 consecutive patients
      with chronic recurrent duodenal ulcer disease (P less than 0.05). Pretreatment
      basal acid output in Zollinger-Ellison syndrome patients ranged from 7.9 to 95.0
      mmol/hr, median 35.2. Pentagastrin-stimulated maximal acid output ranged from 8.5
      to 132 mmol/hr; median 52.7. Acid secretion was lower in the H. pylori-infected
      patients than the uninfected patients (BAO 24.5 +/- 6.5 vs 45.4 +/- 6.6, and MAO
      44.3 +/- 11.8 vs 67.9 +/- 10.7, for H. pylori infected vs uninfected patients,
      respectively). The difference in BAO was statistically significant (P less than
      0.05). The present results indicate that H. pylori is not a major contributing
      factor in duodenal ulcer associated with Zollinger-Ellison syndrome. The
      association of a reduced BAO with H. pylori suggests that these findings may be
      related.

PMID- 1985001
TI  - Improved experimental model for complete gastric vagotomy in the rat.
AB  - Transection vagotomy, dividing both vagal trunks and the esophagus just below the
      diaphragmatic hiatus, is a simple and rapid procedure for vagal denervation of
      the rat stomach. This form of vagotomy is significantly (P less than 0.01) more
      effective than the traditional truncal vagotomy in depressing the basal acid
      output (10.9 mumol +/- 1.4 vs 17.4 mumol +/- 1.8, mean +/- SEM, N = 10). It is
      also more effective (P less than 0.01) than truncal vagotomy in preventing
      reserpine-stimulated gastric acid secretion (9.9 mumol +/- 0.9 vs 20 mumol +/-
      1.5, mean +/- SEM, N = 10). Furthermore, this vagotomy is more powerful (P less
      than 0.01) than truncal vagotomy in combating insulin-stimulated gastric acid
      secretion (10.5 mumol +/- 1.1 and 21 mumol +/- 1.6, respectively vs 169 mumol +/-
      3.8, mean +/- SEM, N = 10). It is, therefore, concluded that the vagal
      denervation of the rat stomach achieved by transection vagotomy is more complete
      than that afforded by truncal vagotomy.

PMID- 1985002
TI  - Chronic effect of intragastric ammonia on gastric mucosal structures in rats.
AB  - The prevalence of Helicobacter pylori (HP) in the gastric mucosa of patients with
      chronic atrophic gastritis has been reported to be significantly higher than in
      normal mucosa. To clarify the role of HP in the etiology of chronic atrophic
      gastritis, we assessed the effect of ammonia on the gastric mucosal structure in
      rats, since HP has a strong urease activity and produces abundant amounts of
      ammonia. Ammonia administered orally at 0.01% and 0.1% as drinking water for two
      to four weeks decreased the mucosal thickness and the parietal cell number and
      oxyntic gland number in a dose- and time-dependent manner. The decrease of
      mucosal thickness was significantly greater in the antral mucosa than in the body
      mucosa. The border between the antral and body mucosa shifted toward the cardia,
      reflecting the decrease in oxyntic gland numbers. Furthermore, intracellular
      mucin was also decreased in a dose- and time-dependent manner, especially in the
      antral mucosa. Thus, ammonia chronically administered orally in rats led to
      changes in gastric mucosal structures and functions. The results suggest that the
      ammonia produced by HP partly plays an etiologic role in chronic atrophic
      gastritis.

PMID- 1985000
TI  - Enhancement of antibiotic concentrations in gastric mucosa by H2-receptor
      antagonist. Implications for treatment of Helicobacter pylori infections.
AB  - We measured the effects of cimetidine on antibiotic concentrations in the luminal
      portion of gastric mucosa. Guinea pigs were premedicated with cimetidine 4 mg/kg
      intramuscularly. Clindamycin, an antibiotic previously characterized under
      physiologic pH conditions, was administered intramuscularly and levels measured
      in serum and tissue using a high-pressure liquid chromatography (HPLC) technique.
      The luminal mucosa concentration of clindamycin at 1 hr (pH 5.9) was fivefold
      greater compared to the concentrations seen under physiologic (pH 2.0) conditions
      (81.5 micrograms/g vs 15.9 micrograms/g; P less than 0.05) and 10-fold greater at
      2 hr (82.7 micrograms/g vs 8.09 micrograms/g; P less than 0.05). There was no
      difference in peak serum levels between the groups. The finding that an
      antibiotic with characteristics of a base is thus affected by a nonconservative
      acid inhibitor such as cimetidine supports the presence of an acidic storage pool
      as proposed by other investigators. H2-receptor antagonists may be useful
      therapeutic adjuncts in H. pylori infections by virtue of increasing gastric
      concentrations of antibiotics that behave as weak bases.

PMID- 1985003
TI  - Mechanism of intragastric nicotine protection against ethanol-induced gastric
      injury.
AB  - To elucidate the mechanism of intragastric nicotine protection against ethanol
      induced gastric mucosal injury seen in a previous report and in our preliminary
      study, the following studies were performed. Rats were pretreated with naloxone
      (8 mg/kg intraperitoneal, 0.5 hr prior to study) to block opiate receptors; or
      capsaicin (125 mg/kg subcutaneous 10 days prior to study) to denervate the
      afferent sensory fibers; or indomethacin (2.5 mg/kg intragastric or 5 mg/kg
      subcutaneous, 1 hr prior to study) to inhibit endogenous prostaglandin synthesis.
      At 1-hr intervals, nicotine (4 mg/kg) or vehicle and 40% ethanol were then given
      intragastrically. Total gastric corpus mucosal lesion length was measured
      unbiasedly. In separate studies, gastric mucosal blood flow (GMBF) was assessed
      by hydrogen gas clearance before and after intragastric nicotine or vehicle;
      luminal mucus volume, gastric juice volume, and acid output were measured 1 hr
      after either intragastric nicotine or vehicle administration. The results showed
      that the acute protective effect of intragastric nicotine was associated with a
      significantly larger luminal mucus volume. It was not blocked by naloxone,
      capsaicin, or indomethacin. There was no increase in GMBF. The larger gastric
      residual volume did not account for the protection. We conclude that the
      mechanism mediating nicotine protection is unique and is independent of opiate
      receptors, capsaicin-sensitive afferent sensory nerve fibers, endogenous
      prostaglandin generation, or dilution of the injurious agent. The increase in
      luminal gastric mucus volume may contribute to the protective effect of
      intragastric nicotine against gastric mucosal injury produced by 40% ethanol.

PMID- 1985004
TI  - Effect of synthetic prostaglandin E1 analog (ornoprostil) on gastric emptying and
      pancreatic polypeptide release after solid-meal ingestion in man.
AB  - The effect of orally administered ornoprostil, 17S,20-dimethyl-6-oxoprostaglandin
      E1 methyl ester, on gastric emptying and on pancreatic polypeptide (PP) release
      after solid meal ingestion, was investigated in man. A radionuclide technique was
      used to measure gastric emptying of eight healthy volunteers. In addition, four
      parameters [SI (starting index): the lag time in the start of emptying; K value:
      the emptying rate; T1/2: the half emptying time; 120 min RR: the percent
      retention at 120 min] were determined for evaluation. Also, the PP response was
      analyzed according to two parameters: IPPRSI the integrated PP response for
      periods up to SI, and IPPR120, the integrated PP response for 120 min. The
      results demonstrated that 5 micrograms of orally administered ornoprostil
      significantly reduced the gastric emptying rate of solid meal (T1/2 and 120 min
      RR, P less than 0.05). However, ornoprostil affected neither the basal PP
      concentrations nor the cephalic phase of PP secretion which was determined as
      IPPRSI. This thus suggests that ornoprostil affects the gastric motor function
      without interfering with the vagal-cholinergic pathway to the stomach.

PMID- 1985005
TI  - Helicobacter pylori and gastric acid output in peptic ulcer disease.
AB  - Helicobacter pylori is associated with peptic ulcer, and a causal relationship
      has been postulated. We investigated the association between Helicobacter pylori
      and gastric acid output. Two hundred forty-one patients were studied: 173 with
      duodenal ulcer, 51 with gastric ulcer (41 corpus, 10 prepyloric), and 17 with
      combined gastric and duodenal ulcer. In 194 patients (80%), Helicobacter pylori
      could be demonstrated histologically from gastric antral biopsies. The presence
      or absence of Helicobacter pylori was not influenced by age, sex, or use of
      tobacco or analgesics. Patients with duodenal ulcer or combined gastric and
      duodenal ulcer had similar gastric acid outputs irrespective of the presence or
      absence of Helicobacter pylori. However, gastric ulcer patients with Helicobacter
      had higher basal and maximal acid outputs when compared to patients without
      Helicobacter (mean basal output: 4.1 mmol/hr vs 2.4, P less than 0.05; mean
      maximal output 19.5 mmol/hr vs. 14.4, P less than 0.05). Although Helicobacter
      pylori is associated with both gastric ulcer and duodenal ulcer, its significance
      may be different in the two diseases.

PMID- 1985007
TI  - Bowel dysfunction in fibromyalgia syndrome.
AB  - Fibromyalgia and irritable bowel syndrome frequently coexist. In this study, we
      utilized a previously validated self-administered questionnaire to assess the
      prevalence of symptoms of bowel dysfunction and irritable bowel syndrome in 123
      patients with fibromyalgia as compared to 54 patients with degenerative joint
      disease (DJD) and 46 normal controls. Ninety (73%) of the fibromyalgia patients
      reported altered bowel function as compared to 20 (37%) DJD patients and none of
      the normal controls (P less than 0.001). Ninety-nine patients (81%) reported
      normal alternating with irregular bowel pattern, and 77 (63%) had alternating
      diarrhea and constipation. In contrast, only 24 (44%) of DJD patients and six
      (13%) of controls had regular alternating with irregular bowel pattern and only
      12 (22%) of the DJD patients and none of the healthy controls had alternating
      constipation and diarrhea (P less than 0.01). Other bowel dysfunction complaints
      noted in the fibromyalgia group were abdominal gas (59%), nausea (21%), diarrhea
      (9%), and constipation (12%). Seventy-nine (64%) fibromyalgia patients reported
      frequent abdominal pain that was stress-related 47% of the time. Laxative use was
      frequent in the fibromyalgia group (19%) and absent in the other two groups.
      Fifty percent of fibromyalgia patients, compared to 28% of DJD patients, felt
      that their bowel complaints were worse during exacerbations of their joint
      disease (P less than 0.05). In conclusion, patients with fibromyalgia have a high
      prevalence of gastrointestinal complaints that should be carefully assessed. If
      the diagnosis of IBS is confirmed, appropriate treatment may improve patients'
      symptoms, although this approach requires further study.

PMID- 1985008
TI  - Scintigraphic assessment of leukocyte infiltration in acute pancreatitis using
      technetium-99m-hexamethyl propylene amine oxine as leukocyte label.
AB  - The infiltration of leukocytes has been linked to the pathophysiology of
      complicated or severe pancreatitis. We have tested the ability of leukocyte
      scintigraphy using technetium-99m-hexamethyl propylene amine oxine (HM-PAO) as
      label to demonstrate the localization of leukocytes in the pancreas during acute
      pancreatitis. Twenty-eight patients with acute pancreatitis (eight with biliary,
      13 with alcoholic, and seven with unknown origin) were studied with leukocyte
      scintigraphy using planar imaging and single photon emission computed tomography
      (SPECT). Fourteen patients had a mild (group I), II a severe (group II), and
      three a lethal outcome (group III) of pancreatitis. All patients of group III,
      six of group II, and two of group I had a positive leukocyte scan. Thus, the
      sensitivity of leukocyte scintigraphy for the detection of a lethal course of
      acute pancreatitis was 100%, of a severe course 54%, and of a severe or lethal
      course 64%. The specificity of a negative scan for a mild pancreatitis was 86%.
      Comparison of the results of leukocyte scintigraphy with those of contrast
      enhanced CT showed that six of eight patients with pancreatic necrosis in CT had
      a positive leukocyte scan, but only five of 20 patients without detectable
      pancreatic necrosis in CT. In summary, leukocyte infiltration into the pancreas
      during pancreatitis can be demonstrated by noninvasive leukocyte scintigraphy
      using technetium-99m-HM-PAO as label. A correlation between the severity of the
      disease and leukocyte infiltration exists.

PMID- 1985009
TI  - Pressure measurements from biliary and pancreatic segments of sphincter of Oddi.
      Comparison between patients with functional abdominal pain, biliary, or
      pancreatic disease.
AB  - Using a minimally compliant infusion system and a triple-lumen pressure recording
      catheter, we obtained endoscopic manometric measurements from both the common
      bile duct and pancreatic duct segments of the sphincter of Oddi (SO) in 58
      patients. Fifteen patients (ages 27-69) had the diagnosis of functional abdominal
      pain, 19 patients (ages 30-76) had partial biliary obstruction, and 24 patients
      (ages 15-80) had idiopathic acute recurrent pancreatitis. Resting ductal pressure
      was similar in the common bile duct and pancreatic duct in all patient groups. In
      the group with functional pain, basal SO pressure was similar, whether obtained
      from the common bile duct or pancreatic duct sphincteric segment. Eight of 19
      patients with partial biliary obstruction had elevated basal SO pressure. Five of
      these eight patients had elevated basal SO pressure confined exclusively to the
      common bile duct segment of the sphincter, while three patients had elevated
      basal SO in both segments. Conversely seven of 24 patients with acute recurrent
      pancreatitis had an elevated basal SO pressure, with five patients having
      pressure elevation only in the pancreatic duct segment while two patients had
      abnormal basal SO pressure in both segments. We conclude that selective
      cannulation of the common bile duct and/or the pancreatic duct during manometric
      study of the SO is necessary in order to diagnose segmental SO dysfunction
      responsible for partial biliary obstruction or episodes of acute recurrent
      pancreatitis.

PMID- 1985006
TI  - Visceral perception in health and functional dyspepsia. Crossover study of
      gastric distension with placebo and domperidone.
AB  - The symptoms of functional dyspepsia are still unexplained. To evaluate the
      possible role of abnormal visceral perception, we studied the symptomatic
      responses and the pressure variations during progressive gastric distension in 10
      female healthy control subjects (mean age 33.6 years) and in 10 female patients
      with functional dyspepsia (mean age 35.2 years). A rubber balloon was positioned
      4 cm below the lower esophageal sphincter (LES) and inflated with progressively
      larger volumes of air by steps of 50 ml; pressures at the gastric fundus and at
      the LES were continuously recorded by perfused manometric catheters. Each subject
      was studied on two separate occasions after randomized double-blind
      administration of either placebo or 20 mg of domperidone. Symptomatic responses
      and the manometric data were analyzed at the time of the initial recognition of
      distension (bloating step) and at the time of reporting pain or up to a maximum
      of 700 ml of balloon inflation (pain or 700-ml step). On placebo, the volumes of
      gastric distension were more than two times lower in patients than in control
      subjects at the bloating step (185 +/- 32 ml vs 470 +/- 40 ml, P = 0.001) and at
      the pain or 700-ml step (265 +/- 54 ml vs 600 +/- 34 ml, P less than 0.005),
      while the pressure gradients (pressure at inflation steps minus baseline pressure
      before beginning inflation) were not statistically different between the two
      groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1985011
TI  - Noninvasive measurement of portal venous blood flow in patients with cirrhosis:
      effects of physiological and pharmacological stimuli.
AB  - The present study aims to evaluate the usefulness of combined pulse Doppler-real
      time ultrasonography as a noninvasive method for the measurement of portal blood
      flow in man. This measurement technique was performed on 12 healthy subjects and
      20 patients with portal hypertension. Ten patients (group 1) were evaluated prior
      to and after ingestion of a standard meal (Ensure Plus) or placebo. In the
      remaining 10 patients (group 2), the effects of isosorbide dinitrate (5 mg/SL)
      administration or placebo were studied. In group 1, food intake caused a
      significant increase of portal blood flow (from 1038 +/- 539 to 1572 +/- 759
      ml/min, P less than 0.02); this effect was due to a significant rise in mean
      blood velocity (from 18.5 +/- 3.7 to 23.9 +/- 3.9 cm/sec, P less than 0.02). In
      group 2, isosorbide dinitrate significantly reduced portal blood flow (from 985
      +/- 491 to 625 +/- 355 ml/min, P less than 0.05); a significant decline of mean
      blood velocity (from 18.8 +/- 4.5 to 14.5 +/- 2.5 cm/sec, P less than 0.02) was
      observed. Placebo administration had no significant hemodynamic effects in either
      group. Our results suggest that Doppler measurements gave accurate noninvasive
      estimations of portal blood flow and that this technique may be used to monitor
      physiological and pharmological stimuli in patients with portal hypertension.

PMID- 1985010
TI  - Penetration of lanthanum through the main pancreatic duct epithelium in cats
      following exposure to infected human bile.
AB  - The main pancreatic duct epithelium acts as a barrier to the diffusion of
      molecules from the duct lumen into pancreatic acinar and interstitial tissue. We
      studied sequential ultrastructural characteristics of the loss of epithelial
      barrier function in the cat using lanthanum, an electron-opaque tracer, following
      perfusion of the duct from the tail to the duodenum with infected human bile.
      Tight junctions between duct epithelial cells were found to become permeable to
      the tracer as early as after 15 min of exposure. Later, there was progressive
      disintegration of intercellular junctions and epithelial loss. Lanthanum
      penetrated the duct epithelium exclusively on an intercellular path. Loss of
      barrier function of the pancreatic duct epithelium was consistently associated
      with subsequent development of acute interstitial edematous pancreatitis. There
      was no association between the degree of duct epithelial damage and the severity
      of acute pancreatitis. Both bile and a suspension of bacteria alone were not
      harmful to the pancreas. Sequential perfusion produced acute pancreatitis only
      when at first bile and then the bacterial suspension was perfused. A reversed
      succession of perfusates produced no morphologic alterations. We conclude: (1)
      Increased tight junction permeability is an early lesion in acute bile-induced
      pancreatitis: (2) loss of duct epithelial barrier function is important for the
      initiation but not for the severity of the inflammation; and (3) bile renders
      duct epithelial intercellular junctions vulnerable to Escherichia coli bacteria.

PMID- 1985012
TI  - Ulcerative proctitis in central Sweden 1965-1983. A population-based
      epidemiological study.
AB  - Ulcerative proctitis has by tradition been regarded as a subgroup of ulcerative
      colitis. Population-based epidemiological studies of ulcerative proctitis are,
      however, virtually nonexistent. In an epidemiological study of inflammatory bowel
      disease in the Uppsala Health Care Region, 1065 cases of ulcerative proctitis
      were diagnosed from 1965 through 1983. Males predominated, with the male to
      female ratio 1.4:1. Annual incidence rates were higher in urban than in rural
      areas. The annual incidence rates increased threefold from 2.8 per 10(5) to 6.6
      per 10(5) during the period, affecting all age groups over 14 years of age, in
      both urban and rural areas and in both sexes. Differences in temporal trends and
      certain other epidemiological characteristics between ulcerative proctitis and
      extensive ulcerative colitis suggest that ulcerative proctitis is a specific
      disease whose etiology differs from that of extensive ulcerative colitis.

PMID- 1985013
TI  - Isolation and characterization of an avian myogenic cell line.
AB  - Myogenic cell lines have proven extremely valuable for studying myogenesis in
      vitro. Although a number of mammalian muscle cell lines have been isolated,
      attempts to produce cell lines from other classes of animals have met with only
      limited success. We report here the isolation and characterization of seven avian
      myogenic cell lines (QM1-4 and QM6-8), derived from the quail fibrosarcoma cell
      line QT6. A differentiation incompetent QM cell derivative was also isolated
      (QM5DI). The major features of QM cell differentiation in vitro closely resemble
      those of their mammalian counterparts. Mononucleated QM cells replicate in medium
      containing high concentrations of serum components. Upon switching to medium
      containing low serum components, cells withdraw from the cell cycle and fuse to
      form elongated multinucleated myotubes. Cultures typically obtain fusion indices
      of 43-49%. Northern blot and immunoblot analyses demonstrate that each
      differentiated QM cell line expresses a wide variety of genes encoding muscle
      specific proteins: desmin, cardiac troponin T, skeletal troponin T, cardiac
      troponin C, skeletal troponin I, alpha-tropomyosin, muscle creatine kinase,
      myosin light chain 2, and a ventricular isoform of myosin heavy chain. While all
      QM lines analyzed to date express at least some myosin light chain 2, only one
      line, QM7, expresses this gene at high levels. Surprisingly, none of the QM lines
      reported here express any known form of alpha-actin. The absence of sarcomeric
      actin expression may explain the absence of myofibrils in QM myotubes. These
      novel features of muscle gene expression in QM cells may prove useful for
      studying the role of specific muscle proteins during myogenesis. More
      importantly, however, the isolation of QM cell lines indicates that it may be
      feasible to isolate other avian myogenic cell lines with general utility for the
      study of muscle development.

PMID- 1985014
TI  - Transgene expression in the QM myogenic cell line.
AB  - We have isolated an avian muscle cell line (QM) which has the essential features
      of established mammalian muscle cell lines. The experiments reported here were
      undertaken to determine the suitability of QM cells for the introduction and
      analysis of cloned transgenes. The promoter of the cardiac troponin T (cTNT) gene
      has been previously shown to contain sequence elements which govern muscle
      specific expression of the chloramphenicol acetyltransferase (CAT) gene in
      transiently transfected primary cell cultures. We show here that QM cells stably
      harboring cTNT promoter-CAT fusion genes up-regulate CAT expression in concert
      with myogenic differentiation, and that as few as 110 upstream nucleotides are
      sufficient for such differentiation-dependent regulation. In addition, both
      transient and stable transfection experiments demonstrate that differentiated QM
      cells possess trans-acting factors necessary for the expression of the skeletal
      alpha-actin promoter, despite the absence of mRNA or protein product from the
      endogenous sarcomeric actin genes in these cells. Finally, to follow the
      developmental potential of QM cells in vivo, we created a clone, QM2ADH, which
      constitutively expresses the histochemical marker transgene encoding Drosophila
      alcohol dehydrogenase. When surgically inserted into the limb buds of developing
      chick embryos, QM2ADH cells are incorporated into endogenous developing muscles,
      indicating that QM cells are capable of recognizing and responding to host cues
      governing muscle morphogenesis. Thus, QM cells are versatile as recipients of
      transgenes for the in vitro and in vivo analysis of molecular events in muscle
      development.

PMID- 1985015
TI  - Expression of transforming growth factor-beta s 1-4 in chicken embryo
      chondrocytes and myocytes.
AB  - cDNA probes and antibodies for TGF-beta s 1, 2, 3, and 4 were used to study the
      expression of these different TGF-beta isoforms in cultured chicken embryo
      chondrocytes and cardiac myocytes, as well as in developing cartilage and heart
      tissues. TGF-beta s 2, 3, and 4 mRNAs, but not TGF-beta 1 mRNA, were detected in
      cultured chondrocytes and myocytes. Expression of TGF-beta s 2 and 4 mRNAs
      increased with age, while expression of TGF-beta 3 mRNA was independent of age in
      chondrocytes cultured from 12- to 17-day-old embryos. In contrast, expression of
      TGF-beta s 2, 3, and 4 mRNAs was constitutive in myocytes cultured from 7- to 9
      day-old embryonic hearts; expression of TGF-beta s 3 and 4 mRNAs increased, while
      expression of TGF-beta 2 mRNA remained unchanged in myocytes from 10-day-old
      embryos. Immunoprecipitation studies demonstrated expression of TGF-beta in both
      the conditioned media and the cell lysates of metabolically labeled chondrocyte
      and myocyte cell cultures. Immunohistochemical staining of cultured chondrocytes
      and myocytes and of cartilage and heart tissues of developing chicken embryos
      with antibodies specific for each TGF-beta isoform showed immunoreactive TGF-beta
      s 1, 2, 3, and 4. Our results demonstrate coordinate expression of these four TGF
      beta isoforms in chicken embryo chondrocytes and myocytes, both in vitro and in
      vivo, with expression of TGF-beta s 2, 3, and 4 mRNA and protein more prominent
      than that of TGF-beta 1.

PMID- 1985016
TI  - Meiotic competence acquisition is associated with the appearance of M-phase
      characteristics in growing mouse oocytes.
AB  - To determine whether the acquisition of meiotic competence during the growth
      phase of oogenesis is associated with the appearance of M-phase characteristics,
      oocytes obtained from 13- to 30-day-old mice were evaluated by fluorescence
      microscopy with respect to chromatin and microtubule organization , in vitro
      maturation ability, and the distribution of M-phase phosphoproteins. Meiotically
      incompetent oocytes were distinguished from their competent counterparts in
      displaying elaborate interphase-like arrays of cytoplasmic microtubules and
      dispersed germinal vesicle chromatin. Meiotically competent oocytes were larger
      in size, exhibited condensation of chromatin around the nucleolus, and displayed
      a progressive diminution of cytoplasmic microtubules in conjunction with the
      appearance of multiple microtubule organizing centers. After 24 hr in culture,
      medium- to large-sized oocytes exhibiting perinucleolar chromatin condensation
      resume meiosis whereas smaller meiotically incompetent oocytes retain GVs with
      diffuse chromatin. Moreover, indirect immunofluorescence studies using the M
      phase phosphoprotein specific monoclonal antibody MPM-2 indicate that the
      appearance of reactive cytoplasmic foci is directly correlated with nuclear
      changes characteristic of meiotically competent oocytes. Thus, the earliest
      transition to a meiotically competent state during oocyte growth in the immature
      mouse ovary is characterized by stage-specific and coordinated modifications of
      nuclear and cytoplasmic components.

PMID- 1985017
TI  - A Brassica S-locus gene promoter targets toxic gene expression and cell death to
      the pistil and pollen of transgenic Nicotiana.
AB  - The S-locus glycoprotein gene of Brassica is derived from the genetic locus that
      controls the self-incompatibility response and the specific recognition between
      pollen and stigma. The promoter of this gene was used to direct expression of the
      diphtheria toxin A chain gene and the Escherichia coli beta-glucuronidase gene in
      transgenic Nicotiana tabacum. Expression of the promoter in cells of the pistil
      and in pollen suggests that a single gene may direct the self-incompatibility
      response in the two interacting cell types. Additionally, the fusion genes were
      expressed gametophytically in the heterologous host species, Nicotiana, rather
      than sporophytically as expected for Brassica. Thus, although the genes involved
      in self-incompatibility in Brassica and Nicotiana are not homologous in their
      coding regions, signals for expression of these genes are apparently conserved
      between the two genera. Our analysis of toxic gene fusion transformants shows
      that genetic ablation is useful for probing developmental processes and for
      studying temporal and spatial patterns of gene expression in plants.

PMID- 1985018
TI  - Reproductive cell specification during Volvox obversus development.
AB  - Asexual spheroids of the genus Volvox contain only two cell types: flagellated
      somatic cells and immotile asexual reproductive cells known as gonidia. During
      each round of embryogenesis in Volvox obversus, eight large gonidial precursors
      are produced at the anterior extremity of the embryo. These cells arise as a
      consequence of polarized, asymmetric divisions of the anteriormost blastomeres at
      the fourth through nine cleavage cycles, while all other blastomeres cleave
      symmetrically to yield somatic cell precursors. Blastomeres isolated from embryos
      at any point between the 2-cell and the 32-cell stage cleaved in the normal
      pattern and produced the same complement and spatial distribution of cell types
      as they would have in an intact embryo. This result indicates that intrinsic
      features control the cleavage patterns and developmental potentials of
      blastomeres, and rules out any significant role for cell-cell interactions in
      gonidial specification. When substantial quantities of anterolateral cytoplasm
      were deleted from uncleaved gonidia or 4-cell stage blastomeres, the cell
      fragments frequently regulated and embryos were produced with the expected number
      of asymmetrically cleaving cells and gonidial precursors at their anterior ends.
      However, when anterior cytoplasm was deleted from 8-cell stage blastomeres, the
      depleted cells frequently failed to cleave asymmetrically and produced no
      gonidial precursors. Furthermore, when compression was used to reorient cleavage
      planes at the fourth division cycle, so that anterior cytoplasm was transmitted
      to more than the normal number of cells, those cells receiving a significant
      amount of such cytoplasm cleaved asymmetrically to produce supernumerary gonidial
      precursors. Together, these last two experiments indicate that blastomeres in the
      V. obversus embryo acquire (at least by the end of the third cleavage cycle) a
      polarized organization in which anterior cytoplasm plays a causal role in the
      process of reproductive-cell specification.

PMID- 1985019
TI  - Participation of the paternal genome is not required before the eight-cell stage
      for full-term development of mouse embryos.
AB  - Differential expression of the paternal and maternal genomes during mouse
      embryonic development is considered a reason for both genomes being required for
      development to term. Extending previous studies performed on two-cell embryos, we
      show here that diploid embryos reconstituted at the four-cell stage from
      uniparental haploid blastomeres can produce living offspring. This result shows
      that for normal development to occur, a paternal genome does not need to be
      associated with a maternal genome within the same nucleus before the eight-cell
      stage.

PMID- 1985020
TI  - Evidence for an adrenergic mechanism in the control of body asymmetry.
AB  - The effect of phenylephrine, an alpha-1 adrenergic agonist, on development of
      body asymmetry was studied using a rat whole embryo culture system. Embryos were
      explanted at the presomite stage, cultured in 100% rat serum containing various
      concentrations of phenylephrine, and examined at the 20-25 somite stage for
      sidedness of asymmetric body structures, namely, bulboventricular loop, allantoic
      placenta, and tail. Phenylephrine treatment resulted in a dose-dependent increase
      of situs inversus with a maximum incidence of 52%. Coadministration of prazosin,
      an alpha-1 adrenergic antagonist, almost completely prevented this effect. Our
      results suggest that receptor-mediated stimulation of the alpha-1 adrenergic
      pathway is involved in the control of normal body asymmetry in developing rat
      embryos.

PMID- 1985021
TI  - Endoderm-specific expression of the Drosophila mex1 gene.
AB  - The Drosophila mex1 gene is one of several genes clustered within a 10-kb
      interval of polytene region 71CD that includes the ecdysone-regulated Eip28/29
      gene. mex1 is expressed in several developmental stages, with gene transcripts
      accumulating initially in 9- to 12-hr embryos. During embryogenesis, mex1
      exhibits an endoderm-specific pattern of expression. mex1 transcripts are first
      detected in the anterior and posterior midgut primordia of stage 12 embryos;
      subsequently, mex1 mRNA accumulates solely in the differentiating embryonic
      midgut. DNA sequence analysis reveals that the mex1 gene encodes an unusual
      cysteine-rich polypeptide.

PMID- 1985024
TI  - Distribution of myosin heavy chain mRNA in embryonic muscle tissue visualized by
      ultrastructural in situ hybridization.
AB  - We have localized myosin heavy chain (MHC) mRNAs in cells of intact embryonic
      chick muscle using high resolution in situ hybridization. Blocks of muscle were
      aldehyde-fixed prior to detergent treatment and hybridized with a biotinated cDNA
      probe, followed by colloidal gold-labeled antibodies, before embedment. Labeling
      was determined to represent MHC mRNA by extensive quantitative comparisons of
      electron micrographs from experimental and four different types of control
      samples. MHC mRNA was localized primarily to peripheral regions of 14-day chick
      pectoral muscle cells, where the majority of developing myofibrils were found.
      MHC mRNAs were consistently associated with the nonmyofibrillar cytoskeletal
      filaments which had diameters ranging from 4 to 10 nm. They were often oriented
      parallel to the longitudinal axis of the cell. The resolution of the
      ultrastructural approach allowed us to demonstrate that the mRNA molecules
      visualized were not directly associated with myofilaments, suggesting that
      nascent chains read from those messages do not assemble directly into
      myofilaments simultaneous with translation.

PMID- 1985027
TI  - A five-year plan of the American Gastroenterological Association.

PMID- 1985026
TI  - The influence of presumptive limb connective tissue on motoneuron axon guidance.
AB  - During embryogenesis in the chick, the lumbosacral (LS) somatopleure gives rise
      to the connective tissue and the epidermis of the limb. We wished to determine if
      the LS somatopleure was a primary source of guidance cues for motoneuron pathway
      choices along the anteroposterior axis of the limb. At stage (st) 15, prior to
      its population by muscle cell precursors and the neural crest, the LS
      somatopleure was shifted anteriorly. This surgery resulted in the development of
      limbs that were shifted one to four segments into the thoracic region. Muscles
      within the anterior thigh of the shifted limb were normally patterned and of
      composite origin: connective tissues were of LS origin, while muscle cells were
      of LS and thoracic origin. Retrograde HRP labeling at st 35-37 indicated that
      motoneuron pools to these anterior thigh muscles were located within LS rather
      than thoracic cord segments. Pools to individual muscles were smaller than normal
      but occupied segmental and transverse positions in the LS cord that generally
      matched those of normal embryos. These findings suggest that individual muscles
      within somatopleure-shifted limbs are innervated specifically and are in accord
      with their connective tissue (and epidermal) level of origin. Reconstructions of
      nerve patterns at st 28-31 suggested that LS motoneurons corrected for the shift
      by altering their pathways at midthigh regions. We conclude that the
      somatopleure, and most likely its connective tissue component, contains the
      information for setting up a specific axon guidance system in the developing
      limb.

PMID- 1985022
TI  - Three linked myosin heavy chain genes clustered within 370 kb of each other show
      independent transcriptional and post-transcriptional regulation during
      differentiation of a mouse muscle cell line.
AB  - We have examined myosin heavy chain gene transcription in the mouse muscle cell
      line C2/7 under different culture conditions. Gene-specific probes for embryonic
      (MHCemb), perinatal (MHCpn), and adult (MHCIIB) MHC sequences were used in
      nuclear run-on experiments, and transcriptional levels compared with cytoplasmic
      RNA accumulation of the transcripts during muscle cell differentiation.
      Transcripts are not detectable in myoblasts. These three MHC genes are physically
      linked within 370 kb of each other. However, they are not activated coordinately,
      but show independent transcriptional regulation as muscle cells differentiate
      into myotubes and as myotubes mature in culture. Post-transcriptional mechanisms
      also regulate cytoplasmic RNA accumulation of these MHC genes.

PMID- 1985025
TI  - Patterns of neurepithelial cell rearrangement during avian neurulation are
      determined prior to notochordal inductive interactions.
AB  - In the epiblast of elongating primitive-streak-stage avian embryos, MHP cells-
      short wedge-shaped neurepithelial cells contained within the median hinge point
      of the bending neural plate--arise from the midline prenodal and nodal area,
      whereas L cells--tall spindle-shaped neurepithelial cells constituting the
      lateral neural plate--arise from paired areas flanking the cranial primitive
      streak. These characteristic differences in neurepithelial cell shape are
      acquired as a result of inductive interactions with the notochord. Both MHP and L
      cells undergo extensive rearrangement (intercalation) during shaping and bending
      of the neural plate, but their pattern of rearrangement differs. MHP cells
      intercalate with other MHP cells and the population always spans the midline,
      whereas L cells intercalate with other L cells, remaining in bulk lateral to the
      midline. The following experiment was performed to establish whether these
      distinctive rearrangement patterns are determined prior to notochordal inductive
      interactions. Quail prospective MHP and L cells were transplanted isochronically
      and heterotopically to chick host blastoderms at stages prior to formation of the
      notochord (to wit, prospective MHP cells were transplanted into prospective L
      cell territory and vice versa) and the distribution, fate, and morphological
      characteristics of grafted cells were determined in chimeras collected 24 hr
      later. Our results demonstrate that heterotopic MHP and L cells do not adopt the
      rearrangement pattern characteristic of their new site; rather, they change their
      position so that grafted MHP cells intermix with MHP cells of the host and
      grafted L cells intermix with L cells of the host. Thus, patterns of
      neurepithelial cell rearrangement are determined prior to notochordal inductive
      interactions. When and how this determination occurs are topics for further
      studies.

PMID- 1985023
TI  - Expression of two mRNAs encoding EGF-related proteins identifies subregions of
      sea urchin embryonic ectoderm.
AB  - Many proteins containing domains related to epidermal growth factor (EGF)
      function in intercellular interactions that mediate specification of cell fate.
      We have used in situ hybridization to show that the expression of two EGF-related
      genes (SpEGF I and SpEGF II) is restricted to the same subset of ectodermal cells
      in sea urchin pluteus larvae. However, the concentration of EGF I mRNA in
      different epithelial cells of aboral ectoderm and postoral facial epithelium is
      constant while that of EGF II mRNA is highly modulated. RNase protection assays
      show that both genes are activated during the period when ectoderm funder cells
      are established, i.e., between fourth and fifth and between fifth and sixth
      cleavages for EGF I and EGF II, respectively. By mesenchyme blastula stage EGF I
      mRNA reaches maximum abundance (800-1000 copies/expressing cell) as a result of a
      high transcription rate, while EGF II mRNA peaks at about half that concentration
      by gastrula stage. EGF I expression begins at early stages of oogenesis while EGF
      II expression appears to be confined to embryogenesis.

PMID- 1985028
TI  - Proximal esophageal pH-metry in patients with 'reflux laryngitis'.
AB  - Fiberoptic laryngoscopic examinations were performed on 40 patients with
      gastroesophageal reflux disease, 25 of whom had persistent laryngeal symptoms
      (dysphonia, cough, globus sensation, frequent throat clearing, or sore throat)
      and 15 without laryngeal symptoms who served as disease controls. Ten patients
      with laryngeal symptoms but none of the controls had laryngoscopic findings
      consistent with reflux laryngitis. Dual-site ambulatory pH recordings were
      obtained with the pH electrodes spaced 15 cm apart and with the proximal sensor
      positioned just distal to the upper esophageal sphincter. Patients in the three
      groups (disease controls: group 1; patients with symptoms but without
      laryngoscopic findings: group 2; and patients with both laryngeal symptoms and
      findings: group 3) were comparable in terms of age, smoking habit, the presence
      of esophagitis, and distal esophageal acid exposure. Proximal esophageal acid
      exposure was, however, significantly increased in groups 2 and 3, and nocturnal
      proximal esophageal acidification occurred in over half of these patients but in
      none of the group 1 patients. We conclude that the subset of reflux patients who
      experience laryngeal symptoms show significantly more proximal esophageal acid
      exposure (especially nocturnally) and often have laryngoscopic findings of
      posterior laryngitis not observed in control reflux patients.

PMID- 1985029
TI  - Partial gastric corpectomy results in hypergastrinemia and development of gastric
      enterochromaffinlike-cell carcinoids in the rat.
AB  - Studies in the rat have shown that partial gastric corpectomy, in which about 75%
      of the acid-producing oxyntic mucosa was removed, leads to markedly reduced acid
      secretion and a feedback increase in the plasma gastrin levels. Ten weeks after
      operation, the gastric enterochromaffin (ECL)-like cell density in the remaining
      part of the oxyntic mucosa had increased significantly. In the present study, the
      effects on the gastric ECL cells of lifelong persistent hypergastrinemia induced
      by partial (75%) corpectomy have been investigated. Seventy-five partially
      corpectomized rats and 40 control rats were investigated for plasma gastrin and
      oxyntic mucosal changes in a 124-week study. The partially corpectomized rats
      showed increased plasma gastrin levels after the operation; the mean increase
      compared with the controls was almost 10-fold during the entire study. The
      remaining oxyntic mucosa of the partially corpectomized rats differed from that
      of control rats in two respects, showing first general hypertrophy and second a
      marked hyperplasia of argyrophil ECL cells. The degree and incidence of these
      changes increased towards the end of the study, i.e., in the aging rats. An age
      related increase in ECL-cell density occurred spontaneously also in the control
      rats but to a lesser extent than in the partially corpectomized group. ECL-cell
      carcinoids were found in the oxyntic mucosa of 26 of the 75 partially
      corpectomized rats. The first carcinoid was found 78 weeks after the beginning of
      the study. Six rats with carcinoids (23%) were found before week 104 (2 years)
      and the remainder, 20 (77%), were discovered later. No carcinoid tumor was found
      in the control rats. It is concluded that lifelong hypergastrinemia induced by
      partial corpectomy leads to the development of ECL-cell carcinoids in the oxyntic
      mucosa of some rats towards the end of their life span. This observation strongly
      supports the hypothesis that the gastric ECL-cell carcinoids found in rats
      treated with antisecretory drugs are caused by long-standing hypergastrinemia
      developing secondary to inhibition of gastric acid secretion.

PMID- 1985030
TI  - Localization of central prostaglandin E2 antisecretory effects.
AB  - Intracerebroventricular prostaglandin E2 (PGE2) inhibits stimulated gastric acid
      secretion; however, the central site of action is unknown. Specific PGE2 binding
      sites have been localized to the ventromedial hypothalamic nucleus and central
      amygdala (A). The nuclear accumbens has been shown to play a role in central
      neurotensin-induced antisecretory effects. These studies tested the hypothesis
      that microinjections of PGE2 into the ventromedial hypothalamic nucleus, central
      amygdala, and nuclear accumbens inhibit stimulated gastric acid secretion. The
      hippocampus served as a cerebral control region. Two days before the experiments,
      metal cannulas were stereotaxically positioned bilaterally into specific areas of
      the brain, and metal gastric cannulas were operatively implanted, under nembutal
      anesthesia, in male 250-g Sprague-Dawley rats. On the experimental day, the rats,
      fasted for 14 hours, were given saline or PGE2 (0.1-1.0 micrograms in 0.2
      microL/side) through the central cannulas 10 minutes before administering
      pentagastrin (40 micrograms/kg SC). Gastric secretion was measured at 30-minute
      intervals and expressed as acid output, micromoles per hour. Acid output (mean +/
      SE) in control animals was 161 +/- 14 mumol/h. Prostaglandin E2 administration
      at doses of 0.10, 0.50, and 1.0 micrograms/side (a) into ventromedial
      hypothalamic nucleus reduced acid output to 53 +/- 11,* 36 +/- 10,* and 27 +/-
      11* mumol/h regularly; (b) into NACB reduced acid output to 157 +/- 36, 60 +/-
      12,* and 38 +/- 12* mumol/h; and (c) into A reduced acid output to 144 +/- 31,
      141 +/- 26, and 90 +/- 19* mumol/h, respectively (*P less than 0.05 by Neuman
      Keuls test). Prostaglandin E2 (0.50 micrograms/side) administration into
      hippocampus had no significant effect on acid output (134 +/- 28 mumol/h).
      Although central PGE2 administration was associated with hyperthermia, this
      occurred at lower doses than those required to inhibit acid secretion.
      Prostaglandin E2 administration into specific brain areas known to have PGE2
      receptors, the central amygdala and ventromedial hypothalamic nucleus, and into
      nuclear accumbens inhibits stimulated gastric acid secretion. These observations
      suggest that PGE2 may have a physiological role in the central control of gastric
      acid secretion.

PMID- 1985031
TI  - Helicobacter pylori infection in pernicious anemia: a prospective controlled
      study.
AB  - Although some authors believe that Helicobacter pylori is the etiologic agent in
      chronic nonspecific gastritis, it has also been suggested that the bacterium
      colonizes inflamed mucosa as a secondary event. This study documents the
      prevalence of H. pylori in 28 patients with pernicious anemia and compares the
      findings with those of a group of 28 age-, race-, and sex-matched asymptomatic
      control subjects. All subjects underwent endoscopy with biopsy of the gastric
      antrum and corpus. A sample of serum was obtained before endoscopy for
      determination of antibodies (immunoglobulin A and immunoglobulin G) to H. pylori.
      The prevalence of H. pylori (by biopsy) in patients with pernicious anemia was
      significantly less than that in controls (11% vs. 71%, P less than 0.0001). All
      patients with pernicious anemia had abnormalities of corpus histology
      (inflammation and/or atrophy). In addition, 50% of patients with pernicious
      anemia had a lymphocytic infiltration of the antrum. All controls with H. pylori
      had gastritis, 50% having active chronic gastritis. Atrophic changes of the
      corpus were more commonly found in patients with pernicious anemia (75% vs. 7%, P
      less than 0.0001). Serology and biopsy results correlated poorly in the patients
      with pernicious anemia: all 5 patients with positive serology results had
      negative biopsy results, whereas all 3 patients with positive cultures on biopsy
      had negative serological studies. In conclusion, patients with pernicious anemia
      are protected from infection with H. pylori, and H. pylori does not passively
      colonize mucosa inflamed by an unrelated process.

PMID- 1985032
TI  - Neuromodulation of guinea pig intestinal electrolyte transport by cholecystokinin
      octapeptide.
AB  - We examined the effect of cholecystokinin octapeptide on electrolyte transport
      across isolated guinea pig mucosa. Segments of distal ileum stripped of
      longitudinal muscle and bathed on both sides with a Krebs'-bicarbonate buffer
      responded to cholecystokinin octapeptide when studied under short-circuited
      conditions. Cholecystokinin octapeptide (0.5-50 nmol/L) evoked a transient (4-10
      minute) increase in transepithelial potential difference and short-circuit
      current upon application to the serosal side. Maximal increases in short-circuit
      current, achieved at 50-500 nmol/L, were 67 +/- 11 microA/cm2, whereas half
      maximal effects occurred at a concentration of 0.7 +/- 0.2 nmol/L. Pretreatment
      of the tissues with 0.5 mumol/L atropine reduced the maximal short-circuit
      response to cholecystokinin octapeptide by 53%. The change in short-circuit
      current due to cholecystokinin octapeptide was nearly abolished by pretreatment
      with 0.5 mumol/L tetrodotoxin, suggesting neuronal involvement. Cholecystokinin
      octapeptide-induced increases in short-circuit current were halved by removal of
      serosal buffer Ca2+ and were abolished in Cl(-)- and HCO3(-)-free buffer. The
      cholecystokin-receptor antagonists proglumide and lorglumide shifted the
      concentration-response curve for cholecystokinin octapeptide competitively to the
      right, having antagonists potencies of 130 and 0.03 mumol/L, respectively.
      Cerulein (0.1-500 nmol/L) also increased short-circuit current, whereas
      nonsulfated cholecystokinin octapeptide was ineffective. In conclusion,
      cholecystokinin octapeptide seems to act at neuronal cholecystokinin receptors to
      stimulate mucosal anion secretion, in part, by releasing acetylcholine.

PMID- 1985033
TI  - The epidemiology of inflammatory bowel disease: a large, population-based study
      in Sweden.
AB  - Previous population-based incidence studies of inflammatory bowel disease are
      limited by small numbers, short duration, or inadequate case-finding. To address
      these problems, we identified all persons with confirmed ulcerative colitis (n =
      2509) or Crohn's disease (n = 1469) in the Uppsala Health Care Region from 1965
      to 1983. Age-specific incidence rates by sex were slightly greater for males with
      ulcerative colitis and females with Crohn's disease. Incidence rates for
      ulcerative colitis and Crohn's disease were higher in urban than rural areas. The
      annual incidence rate of ulcerative colitis increased from less than 7 per
      100,000 to more than 12 per 100,000 during the study period, while the rate for
      Crohn's disease remained between 5 and 7 per 100,000. The increase in the
      incidence of ulcerative colitis was the result of a marked increase in the number
      of patients with ulcerative proctitis. Analyses by 5-year birth cohorts suggest
      that those born from 1945 through 1954 were at higher risk for ulcerative colitis
      and Crohn's disease, and that this effect was accounted for by those born in the
      first half of the year. The seasonality in the cohort effect, combined with the
      urban preponderance of disease, suggests that environmental causes may be
      involved in ulcerative colitis and Crohn's disease.

PMID- 1985034
TI  - Mucosal iron in the control of iron absorption in a rat intestinal transplant
      model.
AB  - Isogeneic intestinal transplantation of iron-loaded and iron-deficient intestine
      into iron-deficient rats was performed in 20 Lewis rats to isolate the effect of
      intestinal mucosal iron on iron absorption. Rats were iron loaded with three
      weekly IM injections of 50 mg of iron dextran and were rendered iron deficient
      with an iron-deficient diet for 3 weeks. Iron status was assessed by hepatic and
      gut mucosal iron determination. Uptake and transfer of 59Fe-ascorbate was
      measured in an isolated perfused segment of transplanted intestine 48 hours after
      transplantation. The mean rate of uptake of 59Fe from an iron-loaded intestine
      (mean mucosal iron concentration, 7.97 +/- 2.02 mumol/g) was 431 +/- 27 nmol/30
      min, and from an iron-deficient intestine (mean mucosal iron concentration, 1.35
      +/- .84 mumol/g), 743 +/- 222 nmol/30 min (P less than 0.001). The mean transfer
      of 59Fe from the mucosal cell to the body through an iron-loaded intestine was 63
      +/- 22 nmol/30 min, and through an iron-deficient intestine was 86 +/- 32 nmol/30
      min (P less than 0.05). These results suggest that the gut mucosal iron
      concentration regulates the uptake and transfer of iron in the intestine.

PMID- 1985037
TI  - Limited tissue distribution of the intestinal brush border myosin I protein.
AB  - A myosinlike 105-110-kilodalton calmodulin-binding protein, brush border myosin
      I, found in the intestinal brush border has been linked to two seemingly
      disparate but possibly interacting functions of the brush border, namely,
      microvillar motility and vitamin D regulated calcium transport. If brush border
      myosin I were to function primarily as a myosinlike molecule powering cellular or
      microvillar motility, one might expect it to be found in a variety of tissues
      with microvilli such as the renal brush border and bile canaliculus. On the other
      hand, a more specialized function such as participation in vitamin D regulated
      calcium transport might dictate a more restricted tissue distribution for brush
      border myosin I. To determine the tissue distribution of brush border myosin I,
      we purified this protein to apparent homogeneity, generated antisera to it, and
      used the antisera to localize the protein within the intestinal epithelial cell
      by immunocytochemistry. We then screened a variety of other tissues (brain, lung,
      heart, liver, spleen, pancreas, kidney, and skeletal muscle) both for calmodulin
      binding proteins as well as for brush border myosin I using Western blots and
      immunofluorescence. Our results indicate that the intestinal brush border myosin
      I is limited in its distribution to the intestinal brush border.

PMID- 1985036
TI  - Intestinal effects of the products of lipid digestion on gastric electrical
      activity in the cat. Possible involvement of vagal intestinal receptors sensitive
      to lipids.
AB  - The relationship between the lipid content of the intestinal lumen and gastric
      motor activity was studied in anesthetized cats. For this purpose the
      electromyographic activity was recorded in the antrum whereas the small intestine
      (duodenum and first part of jejunum or ileum) was perfused with various solutions
      including calcium propionate, tributyrin, sodium caprylate, potassium oleate,
      mixtures containing linoleic acid, monolein, triolein, mixture of triglycerides,
      and glycerol. Long-chain lipids and glycerol both induced a decrease in the rate
      of basal antral activity. This effect was found to depend on the state of lipid
      hydrolysis (triglycerides, monoglycerides, and fatty acids) and was most marked
      with monolein, linoleic acid, and glycerol. With the middle-chain lipids used,
      these effects were only slight; short-chain lipids did not induce any visible
      changes in gastric activity. All these effects were prevented by cervical
      bivagotomy. It was concluded that the two types of lipid-sensitive vagal
      receptors, which we recently showed to exist in the small intestine, trigger an
      inhibitory enterogastric reflex that contributes to the regulation of gastric
      emptying.

PMID- 1985035
TI  - Induction of pS2 and hSP genes as markers of mucosal ulceration of the digestive
      tract.
AB  - The recently discovered pS2 protein is expressed under estrogen control in a
      subset of estrogen receptor-positive breast cancers and in an estrogen
      independent manner in normal stomach mucosa. The pS2 gene belongs to a family of
      genes encoding peptides that contain a conserved 5-cysteine domain, the P
      domains. Although the function of the pS2 protein is unknown, it has been
      suggested that it may have cell growth stimulatory activity. We report here that
      expression of the pS2 gene in the digestive tract, which is normally restricted
      to the stomach, is strongly induced by mucosal ulcerations elsewhere in the
      tract, most notably in Crohn's disease. pS2 gene expression is restricted to the
      mucosal layers adjacent to the ulcerations, in a region where a novel epidermal
      growth factor-secreting cell lineage was shown to be induced by mucosal
      ulceration. The human hSP gene, which contains a tandem duplication of the pS2
      gene P domain and is coexpressed with the pS2 gene in normal stomach mucosa but
      not in breast cancers, is also expressed in Crohn's disease. We suggest that pS2
      gene expression may provide a useful marker for mucosal ulcerations of the
      digestive tract.

PMID- 1985038
TI  - Colonic glycoproteins in monozygotic twins with inflammatory bowel disease.
AB  - Colonic glycoprotein composition was evaluated in monozygotic twins with
      inflammatory bowel disease using ion-exchange chromatography. Fifty-three
      individuals, 12 pairs and 1 single twin with ulcerative colitis and 14 pairs with
      Crohn's disease, were evaluated. Seven twin pairs were concordant for the
      presence of ulcerative colitis or Crohn's disease, whereas twin siblings of 10
      ulcerative colitis probands and 9 Crohn's disease probands were not known to have
      inflammatory bowel disease. Content of one chromatographically defined component
      of colonic mucin, designated HCM species IV, was reduced in both patients with
      ulcerative colitis (1040 +/- 300 cpm/10,000 cpm total HCM) and their apparently
      healthy twins (1340 +/- 540 cpm/10,000 cpm total HCM) compared with control
      subjects (4030 +/- 1,000 cpm/10,000 cpm total HCM). Composition of mucin in
      Crohn's disease patients and their nonaffected twins was not significantly
      different than in controls. These observations suggest that altered profiles of
      mucin glycoprotein may be present before the onset of ulcerative colitis and may
      be genetically defined. Conversely, it appears that alterations in glycoproteins
      only are not sufficient to initiate mucosal inflammation.

PMID- 1985039
TI  - The anal sphincter in patients with myotonic muscular dystrophy.
AB  - The objective of this prospective study was to determine anal sphincter function
      and thickness of the anal musculature in patients with myotonic muscular
      dystrophy. Manometric studies were performed in 16 patients with myotonic
      dystrophy and in 16 healthy controls. Patients had significantly lower basal and
      squeeze pressures than control subjects (P less than 0.01). The results of
      ultrasonographic studies of the anal canal in 7 patients and 7 control subjects
      suggest that this decrease in muscle strength is partly explained by muscular
      atrophy. In addition, patients with myotonic dystrophy showed exaggerated rebound
      contractions following and sphincter relaxation that was induced by rectal
      distention. The pattern of this response and the results of electromyographic
      studies in 6 patients with myotonic dystrophy suggest that such abnormalities are
      explained by a neurogenic defect rather than a myotonic response of the anal
      musculature. It is concluded that patients with myotonic dystrophy show a
      multitude of defects in the anal sphincter that are an expression of myopathy,
      muscular atrophy, and neural abnormalities.

PMID- 1985040
TI  - Role of hypothalamic cholecystokinin octapeptide in the colonic motor response to
      a meal in rats.
AB  - The effects of hypothalamic microinfusions of cholecystokinin octapeptide and its
      antagonist L364,718 on cecocolonic myoelectrical activity were evaluated by
      electromyography in fasted and fed rats. The rats were chronically fitted with
      electrodes implanted on the cecum and proximal colon and cannulas placed
      bilaterally in either the ventromedial or lateral hypothalamus. In fasted rats,
      microinfusion of cholecystokinin octapeptide (10 ng/kg) into the ventromedial
      hypothalamus increased the spike-burst frequency of the cecum and the colon by
      45.6% and 43.7%, respectively, during the 30-minute period after treatment. The
      injection of cholecystokinin octapeptide (10 ng/kg) into the lateral hypothalamus
      had no effect on either cecal or colonic motility. Feeding increased the
      frequency of cecal and colonic spike bursts by 52.1% and 50.1% for 30 minutes
      postprandially. When infused bilaterally into the ventromedial hypothalamus 10
      minutes before feeding, L364,718 (1 or 5 micrograms/kg) abolished the increase of
      the frequency of cecal and colonic contractions induced by the meal. Infused into
      the lateral hypothalamus at similar dosages, L364,718 had no effect on the
      postprandial enhancement of cecocolonic motility. Increase of cecocolonic spike
      burst frequency induced by feeding or by cholecystokinin octapeptide injected
      into the ventromedial hypothalamus was abolished by previous
      intracerebroventricular but not intraperitoneal administration of atropine (1
      microgram) and 4-diphenylacetoxy-N-methylpiperidine (1 microgram), a selective
      muscarinic M2-receptor antagonist. In contrast, pirenzepine (1 microgram,
      intracerebroventricularly) did not significantly reduce the meal- or
      cholecystokin octapeptide-induced increase in cecal and colonic motility. These
      results suggest that, in rats, (a) cholecystokinin octapeptide is involved in the
      generation of the cecocolonic motor response to a meal and these effects are
      mediated through cholecystokinin octapeptide receptors located in the
      ventromedial hypothalamic nuclei, and (b) these postprandial colonic motor
      changes involve central cholinergic activation through muscarinic M2 receptors.

PMID- 1985041
TI  - A controlled trial of psychological treatment for the irritable bowel syndrome.
AB  - One hundred two patients with irritable bowel syndrome were studied in a
      controlled trial of psychological treatment involving psychotherapy, relaxation,
      and standard medical treatment compared with standard medical treatment alone.
      Patients were only selected if their symptoms had not improved with standard
      medical treatment over the previous 6 months. At 3 months, the treatment group
      showed significantly greater improvement than the controls on both
      gastroenterologists' and patients' ratings of diarrhea and abdominal pain, but
      constipation changed little. Good prognostic factors included overt psychiatric
      symptoms and intermittent pain exacerbated by stress, whereas those with constant
      abdominal pain were helped little by this treatment. This study has demonstrated
      that psychological treatment is feasible and effective in two thirds of those
      patients with irritable bowel syndrome who do not respond to standard medical
      treatment.

PMID- 1985043
TI  - Anorectal sensory and motor function in neurogenic fecal incontinence. Comparison
      between multiple sclerosis and diabetes mellitus.
AB  - We measured anorectal sensory and motor function in 11 patients with multiple
      sclerosis and fecal incontinence, 11 continent patients with multiple sclerosis,
      10 diabetics with fecal incontinence, and 12 healthy control subjects. The
      threshold volume at which patients with multiple sclerosis and fecal incontinence
      experienced rectal sensation was higher than that in healthy controls (42.7 +/-
      6.2 mL vs. 13.3 +/- 2.8 mL; P less than 0.01) and was similar to that in
      incontinent diabetics (36.5 +/- 5.7 mL). Patients with multiple sclerosis and
      incontinent diabetics also showed increased thresholds of phasic external
      sphincter contraction compared with controls (P less than 0.05). Diabetics with
      incontinence had reduced resting and maximal voluntary anal sphincter pressures
      compared with controls (P less than 0.05), whereas patients with multiple
      sclerosis and incontinence showed only decreased maximal voluntary anal sphincter
      pressures (P less than 0.01 vs. controls and diabetics). Incontinent patients
      with multiple sclerosis also required smaller volumes of rectal distention to
      inhibit internal sphincter tone compared with diabetics and controls (P less than
      0.01). Decreased maximal voluntary squeeze pressures were less severe in
      continent patients with multiple sclerosis than in incontinent patients with
      multiple sclerosis. We conclude that impaired function of the external anal
      sphincter and decreased volumes of rectal distention to inhibit the internal anal
      sphincter or both may contribute to fecal incontinence in multiple sclerosis. In
      addition, increased thresholds of conscious rectal sensation in some incontinent
      patients with multiple sclerosis and diabetes mellitus may contribute to fecal
      incontinence by impairing the recognition of impending defecation.

PMID- 1985042
TI  - Multifocal colitis associated with an epidemic of chronic diarrhea.
AB  - An outbreak of a chronic diarrheal syndrome was detected between May and August
      1987 in rural Henderson County, Illinois. Seventy-two individuals were affected.
      Epidemiological studies performed by the Center for Disease Control implicated
      the water of a local restaurant as the source of the outbreak. Five patients
      underwent a comprehensive evaluation. Their mean age was 51 years, and they had a
      mean of 12 watery stools daily (range, 6-40). Detailed microbiological
      evaluations failed to identify a pathological organism. Stool studies showed a
      mean stool weight of 392 g/24 h with a normal fat content. Results of all
      biochemical studies of serum were normal. Chemical analysis of stool water
      suggested a secretory diarrhea. Colonoscopy revealed patchy erythema, and light
      microscopic examination of colonic biopsy specimens revealed multifocal areas of
      acute inflammation in the superficial mucosa in 4 of 5 patients. Electron
      microscopy of the affected areas revealed no viral particles. After 2 years, all
      of our patients continued to experience chronic diarrhea. One patient agreed to a
      follow-up colonoscopy; histological abnormalities of the colonic mucosa persisted
      after 2 years. We speculate that an infectious process arising from a
      contaminated water system induced a chronic, secretory diarrhea characterized by
      multifocal colitis. This histological abnormality may serve as a marker of an
      infectious, chronic diarrhea.

PMID- 1985044
TI  - Diarrhea in ciguatera fish poisoning: preliminary evaluation of
      pathophysiological mechanisms.
AB  - Ciguatera fish poisoning is a clinical syndrome consisting of a combination of
      gastrointestinal and neurological symptoms occurring after eating toxin
      containing tropical reef fish; it is a major cause of morbidity in Hawaii, the
      South Pacific, Australia, and the Caribbean. In an effort to define
      pathophysiological mechanisms responsible for the diarrheal component of the
      illness, we examined the effect of crude and fractionated toxin preparations on
      isolated rabbit ileal tissue in a Ussing chamber model. Both the crude toxin
      preparation (prepared from toxic Ctenochaetus strigosus) and 10% and 50% methanol
      chloroform toxin fraction (prepared from a pool of toxic fish samples) gave a
      striking increase in transepithelial electrical potential difference and short
      circuit current. Enterotoxic activity seemed to be mediated by calcium. When
      examined by light microscopy, the intestinal mucosa was not damaged by the toxin
      preparations used. Our data demonstrate that toxins involved in ciguatera fish
      poisoning directly stimulate intestinal fluid secretion without accompanying
      tissue damage and suggest that calcium is the "second messenger" mediating the
      process.

PMID- 1985045
TI  - Selective intestinal decontamination prevents spontaneous bacterial peritonitis.
AB  - In a prospective randomized study, selective intestinal decontamination with
      norfloxacin was performed during hospitalization in 32 cirrhotic patients with
      low ascitic fluid total protein levels. The incidence of infections was compared
      with that in a control group of 31 nontreated cirrhotic patients of similar
      characteristics. We found a significantly lower incidence of infections [1/32
      (3.1%) vs. 13/31 (41.9%); P less than 0.005] and spontaneous bacterial
      peritonitis [0/32 (0%) vs. 7/31 (22.5%); P less than 0.05] in patients receiving
      norfloxacin. The lower incidence of extraperitoneal infections [1/32 (3.1%) vs.
      7/31 (22.5%); P = 0.052] in the treated group did not reach statistical
      significance. The incidence of infections [1/28 (3.6%) vs. 9/22 (40.9%); P less
      than 0.01] and spontaneous bacterial peritonitis [0/28 (0%) vs. 5/22 (22.7%); P
      less than 0.05] in cirrhotic patients admitted because of ascites was also
      significantly lower in the treated group. The decrease in the rate of mortality
      observed in the group undergoing selective intestinal decontamination did not
      reach statistical significance. These data show that selective intestinal
      decontamination is useful to prevent spontaneous bacterial peritonitis and
      extraperitoneal infections in hospitalized cirrhotic patients with low ascitic
      fluid total protein levels.

PMID- 1985046
TI  - A rodent model of cirrhosis, ascites, and bacterial peritonitis.
AB  - We sought to develop a rodent model of spontaneous bacterial peritonitis and
      report here the preliminary results of carbon tetrachloride-induced cirrhosis in
      which ascites and bacterial peritonitis predictably develop. Of 41 rats that
      survived the initial carbon tetrachloride toxicity, 38 (92.7%) developed
      cirrhosis with ascites. Of these 38, 21 (55.3%) developed 24 episodes of ascitic
      fluid infection without iatrogenic colonization. No surgically treatable source
      of infection was identified at autopsy in any rat; therefore, the infections were
      presumed to be "spontaneous." Eight (50%) of the 16 rats with culture-positive
      ascitic fluid at postmortem examination also had spontaneous pleural fluid
      infection with the same organism. Escherichia coli and Proteus sp. were the
      organisms most commonly isolated. This rodent model of cirrhosis with ascites
      appears to be the first high-yield animal model of spontaneous bacterial
      peritonitis. Ascitic fluid infection in these rats resembles ascitic fluid
      infection in humans. This model will allow further investigation of the
      mechanisms of pathogenesis of ascitic fluid infection and provide insight into
      the prevention and treatment of spontaneous bacterial peritonitis and pleural
      fluid infection in patients with cirrhosis.

PMID- 1985047
TI  - Hepatic injury associated with small bowel bacterial overgrowth in rats is
      prevented by metronidazole and tetracycline.
AB  - Susceptible rat strains develop hepatobiliary injury following the surgical
      creation of self-filling blind loops that cause small bowel bacterial overgrowth.
      Luminal bacteria or their cell wall polymers were implicated in the pathogenesis
      of the lesions because sham-operated rats and rats with self-emptying blind
      loops, having only slightly increased bacterial counts, did not develop hepatic
      injury. In this study, antibiotics with different spectra of activities were
      continuously administered starting 1 day or 22 days after surgery to determine
      which intestinal flora may be responsible for the development of hepatic injury
      in rats with small bowel bacterial overgrowth. Four weeks following surgery,
      Lewis rats with self-filling blind loops receiving no antibiotics had elevated
      liver histology scores (8.2 +/- 1.3 vs. 0.7 +/- 0.4) and plasma aspartate
      aminotransferase levels (269 +/- 171 vs. 84 +/- 24) compared with sham-operated
      rats, P less than 0.001. Oral gentamicin as well as oral and intraperitoneal
      polymyxin B, which binds endotoxin, did not prevent hepatic injury in rats with
      self-filling blind loops. However, oral metronidazole and tetracycline therapy
      continuously administered beginning 1 day after surgery diminished hepatic injury
      (histology score 3.0 +/- 1.8, 2.9 +/- 1.1; aspartate aminotransferase 87 +/- 25,
      98 +/- 34; respectively P less than 0.001 compared with self-filling blind loops
      receiving no antibiotics). Metronidazole also protected Wistar rats that require
      12 weeks to develop hepatic injury following experimentally induced small bowel
      bacterial overgrowth compared with rats with self-filling blind loops that
      received no antibiotic treatment (histology score 10.4 +/- 1.3 vs. 0.7 +/- 1.1,
      and aspartate aminotransferase 273 +/- 239 vs. 76 +/- 20, P less than 0.001).
      When rats started metronidazole therapy 22 days after self-filling blind loop
      surgery, elevated aspartate aminotransferase values decreased to normal during
      the next 77 days and final histology scores were normal. All rats with self
      filling blind loops had negative peritoneal, liver, spleen, and blood cultures
      but approximately 75% of mesenteric lymph node cultures were positive
      irrespective of antibiotic treatment. Because Bacteroides species have been
      implicated in causing vitamin B12 and disaccharidase deficiencies in rats with
      self-filling blind loops, we documented the presence or absence of these
      organisms from blind loops using selective culture techniques. Metronidazole and
      tetracycline eliminated Bacteroides sp. from blind loops, but polymyxin B and
      gentamicin did not.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1985049
TI  - Patterns of growth and metastases of induced pancreatic cancer in relation to the
      prognosis and its clinical implications.
AB  - To understand high malignancy of pancreatic cancer, the growth and metastatic
      patterns of pancreatic cancer induced in Syrian hamsters were examined. In this
      model, induced tumors resemble the human disease morphologically, clinically,
      biologically, and immunologically. In the current study, primary-induced cancer
      and transplants of pancreatic cancer cell line (PC-1) into the SC tissue or
      pancreas of homologous hosts were used. In the primary-induced pancreatic cancer,
      perineural invasion was the most common path (88%), followed by lymphogenic (31%)
      or vascular (2%) metastases. Inoculation of PC-1 cells into the pancreas resulted
      in 100% tumor take within 3 weeks. Of 19 intrapancreatic allografts, all showed
      peritoneal invasion, 5 (26%) liver metastases, 3 (16%) lymph node metastases, 17
      (89%) perineural invasion, and none vascular invasion. Even microscopic tumors
      were found to metastasize primarily via perineural spaces. It was also
      demonstrated, for the first time, that cancer cells take this route to reach
      distant tissues, including the lymph nodes. Intraductal spreading occurred in
      both primary cancers and intrapancreatic allografts either continuously or
      discontinuously. The patterns of discontinuous intraductal tumor expansion
      imitated tumor multicentricity. Although perineural invasion was the most common
      feature of primary cancer and intrapancreatic allografts, lymphatic, hepatic, and
      vascular invasion and metastases usually occurred in advanced cases.
      Environmental factors seem to influence expansion and metastases, as evidenced by
      differences in growth and in metastatic patterns between SC and intrapancreatic
      allografts.

PMID- 1985048
TI  - Pulmonary hypertension complicating portal hypertension: prevalence and relation
      to splanchnic hemodynamics.
AB  - The prevalence of pulmonary hypertension in 507 patients hospitalized with portal
      hypertension but without known pulmonary hypertension who underwent cardiac
      catheterization was prospectively studied. Ten (2%) of these patients, 6 of whom
      were clinically asymptomatic, had primary pulmonary hypertension. Second, 26
      patients with symptomatic pulmonary hypertension complicating portal hypertension
      were reviewed. Pulmonary hypertension occurred later after diagnosis of portal
      hypertension in patients with a surgical shunt (10 patients) than in those
      without a shunt (147 +/- 49 vs. 44 +/- 27 months; P less than 0.0001). Cardiac
      index correlated inversely with pulmonary arterial pressure (r = -0.45; P less
      than 0.01) and was lower in the 5 patients who died of pulmonary hypertension
      than in the 5 who died of liver failure (1.52 +/- 0.14 vs. 3.69 +/- 1.88
      L/min.m2; P less than 0.05). Third, systemic and splanchnic hemodynamics were
      compared in 285 patients with alcoholic cirrhosis and 29 controls. No significant
      relation was found between elevated pulmonary vascular resistance and increased
      portal pressure, zzygos blood flow, or cardiac index. Pulmonary hypertension is
      considerably more frequent than was previously estimated in patients with portal
      hypertension. The risk of developing pulmonary hypertension could increase with
      the duration of portal hypertension without any clear relation to the degree of
      portal hypertension, hepatic failure, or amount of blood shunted.

PMID- 1985050
TI  - Recurrent acute fatty liver of pregnancy associated with a fatty-acid oxidation
      defect in the offspring.
AB  - A case of a 29-year-old woman who has had two episodes both clinically and
      biochemically consistent with acute fatty liver of pregnancy is described. These
      episodes occurred in two successive pregnancies, and liver biopsy confirmed the
      diagnosis in the second pregnancy. Both pregnancies were managed by prompt fetal
      delivery; on both occasions this led to a complete biochemical resolution of the
      liver function abnormalities. Two healthy babies were delivered by ceasarian
      sections. This case is of particular importance because a rapidly progressive and
      devastating illness developed in both infants, leading to death at 6 1/2 and 6
      months, respectively. The illness in both babies was characterized by wide-spread
      fatty infiltration of several vital organs and a failure of any treatment to
      influence the outcome of that illness. Studies suggested that the illness in the
      children was caused by a still ill-defined disorder of fatty acid oxidation. The
      biochemical disorder evidenced in this family is discussed, in an attempt to shed
      light on the etiology of acute fatty liver of pregnancy.

PMID- 1985051
TI  - Neutrophil dysfunction in glycogen storage disease Ib: association with Crohn's
      like colitis.
AB  - Two cases of patients with Crohn's-like colitis and glycogen storage disease Ib
      have been reported previously. In the current report, chronic inflammatory bowel
      disease that developed in another adolescent with this glycogenosis is described,
      thereby corroborating the association. The neutrophil dysfunction observed in
      glycogen storage disease Ib is the most likely predisposing factor. Neutrophil
      function was investigated in our patient in an attempt to shed light on the
      pathogenesis of his intestinal inflammation. The patient displayed reduced
      neutrophil chemotaxis to zymosan-activated serum, N-formyl-methionine
      phenylalanine, and Escherichia coli bacteria-derived factor and reduced
      intracellular killing of Staphylococcus aureus 502A. Others have found this
      defective bacteriocidal activity to be caused by impaired oxidative metabolism.
      The recent recognition of chronic inflammatory bowel disease in glycogen storage
      disease Ib, as well as in chronic granulomatous disease, suggests that further
      study of respiratory burst activity of neutrophils in Crohn's disease is
      warranted.

PMID- 1985052
TI  - Granulocytic sarcoma of the colon.
AB  - Granulocytic sarcoma is an extramedullary tumor consisting of immature cells of
      the granulocytic series known to occur in patients with myelodysplastic syndrome,
      chronic myelogenous leukemia, or acute myelogenous leukemia. This tumor may
      involve nodes, cervix, bone and periosteum, and infrequently the small intestine.
      Granulocytic sarcoma rarely occurs in the colon and has not been previously
      described endoscopically. We encountered a 73-year-old man with myelodysplastic
      syndrome who presented with fever, diarrhea, and abdominal pain. Colonoscopic
      evaluation (focal ulceration, friability, and nodularity) was compatible with
      Crohn's disease, although histology showed a dense myeloid cell infiltrate
      characteristic of granulocytic sarcoma. In patients with myelodysplastic syndrome
      or acute or chronic myelogenous leukemia presenting with diarrhea, abdominal
      pain, and/or fever, colonoscopy and biopsy are indicated to determine if the
      colon is affected by granulocytic sarcoma.

PMID- 1985053
TI  - Localization of calcitonin gene-related peptide in human esophageal Langerhans
      cells.
AB  - Previously undescribed calcitonin gene-related peptide-immunoreactive
      intraepithelial cells were seen in specimens of esophageal mucosa obtained by
      biopsy or surgical resection from 14 individuals. These calcitonin gene-related
      peptide-immunoreactive cells were sparsely seen in normal mucosa but increased
      markedly in esophagitis. They were inaccessible to routine histological stains,
      but osmication showed them as dendritic forms resembling Langerhans cells of the
      skin. Their cytological identity was determined with immunocytochemical tests for
      human antigenic markers such as Ia, HLA-DR, and OKT6 for Langerhans cells, Leu-M5
      and Leu-M3 for intraepithelial macrophages, CD3 and TCR-1 for T-lymphocytes, Leu
      14 for B-lymphocytes, S-100 for Merkel cells, and chromogranin for amine
      precursor uptake and decarboxylation cells. Double localization showed that
      calcitonin gene-related peptide immunoreactivity colocalized with Ia, HLA-DR, and
      OKT6 but not with the other markers. These studies show that intraepithelial
      Langerhans cells in the esophageal mucosa contain calcitonin gene-related
      peptide, which may serve as an immunomodulator.

PMID- 1985054
TI  - Hyperplastic polyps seen at sigmoidoscopy are markers for additional adenomas
      seen at colonoscopy.
AB  - Asymptomatic individuals undergoing screening flexible sigmoidoscopy were
      prospectively studied. Polyps were found in 185 subjects. The endoscopist
      recorded an opinion on the polyps' histology based on endoscopic appearance. No
      polyps were removed at sigmoidoscopy. All subjects with rectosigmoid polyps then
      underwent colonoscopy and polypectomy. Of them, 99 subjects (54%) had at least
      one rectosigmoid adenoma, 69 (37%) had only hyperplastic polyps, and 17 (9%) had
      other findings. The endoscopists' opinion of the histopathology of polyps at
      sigmoidoscopy was correct for 61% of the lesions. Of subjects with adenomatous
      rectosigmoid polyps, 29% had additional adenomas at more proximal sites. Proximal
      adenomas were found in 28% of patients with hyperplastic rectosigmoid polyps.
      Patients with rectosigmoid hyperplastic polyps had the same risk for additional
      proximal adenomas as patients with rectosigmoid adenomatous polyps.

PMID- 1985055
TI  - Cirrhosis and portal hypertension in a patient with adult Niemann-Pick disease.
AB  - A woman with known Niemann-Pick disease, type B, presented at age 33 with upper
      gastrointestinal bleeding, ascites, and peripheral edema. Evaluation showed
      massive hepatosplenomegaly, infiltration of the liver with Niemann-Pick cells,
      cirrhosis, and evidence of portal hypertension. Chronic gastrointestinal
      bleeding, thrombocyctopenia, and platelet dysfunction were treated successfully
      by splenectomy. Cirrhosis and portal hypertension have not been reported
      previously in adult Niemann-Pick disease in the absence of some other cause.

PMID- 1985056
TI  - Colonoscopic surveillance for cancer in patients with chronic ulcerative colitis:
      is it working?

PMID- 1985057
TI  - Cajal has the nerve to set the pace in the colon.

PMID- 1985058
TI  - Duodenal ulcer disease--to heal or to cure?

PMID- 1985059
TI  - Endoscopic therapy for peptic ulcer hemorrhage: heater probe and alcohol
      injection.

PMID- 1985060
TI  - Hepatitis A: more food for thought.

PMID- 1985061
TI  - Mucolytic agents and cholesterol gallstones.

PMID- 1985062
TI  - Is radical scavenging necessary in the treatment of inflammatory bowel disease?

PMID- 1985063
TI  - Hepatocytes and intrahepatic bile duct epithelium originate from a common stem
      cell.

PMID- 1985064
TI  - Cost-effectiveness of maintenance [correction of mentense] H2 blockers in peptic
      ulcer disease.

PMID- 1985065
TI  - Retinopathy in pancreatic diabetes.

PMID- 1985066
TI  - Work history is too often overlooked.

PMID- 1985067
TI  - Flu vaccination plus amantadine effective in nursing home.

PMID- 1985068
TI  - Congestive heart failure: a current overview.
AB  - Congestive heart failure (CHF), a disease seen primarily in the older patient,
      can be due to either systolic or diastolic dysfunction. Management is quite
      different if the heart failure is due to a filling abnormality as compared to
      poor ventricular systole. The disorder also poses many diagnostic pitfalls in the
      elderly. Current understanding of CHF and its influence on diagnosis and
      management is the focus of this review.

PMID- 1985069
TI  - Managing prostatitis in the elderly.
AB  - Bacterial prostatitis is primarily a disease of elderly men, and it is the most
      common urinary tract infection seen in this age group. Urosepsis from prostatitis
      or prostatic abscess occurs less frequently than with urological manipulation,
      but must always be considered in elderly men with prostatitis. This article
      focuses on the diagnosis and antibiotic treatment of bacterial prostatitis in the
      elderly.

PMID- 1985070
TI  - Diagnosing and treating depression in the hospitalized elderly.
AB  - The interactions between depression and medical illness are complex, especially
      in the elderly patient, and particularly in the hospital setting. Differential
      diagnosis in this population is quite broad, encompassing both psychiatric and
      medical etiologies. With appropriate diagnosis, treatment of depression in the
      hospitalized elderly is extremely effective and can both improve quality of life
      and decrease health resource utilization.

PMID- 1985071
TI  - Playing the red tape blues.

PMID- 1985072
TI  - Eosinophilia-myalgia.

PMID- 1985073
TI  - L-tryptophan and the eosinophilia-myalgia syndrome: pathologic findings in eight
      patients.
AB  - Pathologic findings in eight patients with the eosinophilia-myalgia syndrome,
      secondary to L-tryptophan ingestion, are reported. Tissue was obtained by biopsy
      alone in six patients, by biopsy and autopsy in the seventh patient, and by
      autopsy alone in the eighth patient. Muscle biopsies in five patients
      demonstrated an inflammatory infiltrate composed predominantly of lymphocytes,
      histiocytes, plasma cells, and a few eosinophils. The inflammation involved the
      perimysial and epimysial connective tissue, the walls of some small blood
      vessels, the perineurium of small nerve twigs, muscle spindles, and fibrous
      septae of subcutaneous adipose tissue. In two patients with peripheral neuropathy
      and one patient without overt neuropathy, denervation atrophy of muscle and
      perimysial and epimysial fibrosis were present. Sural nerve biopsy tissue taken
      from two patients displayed prominent axonopathy in one, and minimal changes in
      the second. Pulmonary changes in the two autopsied patients included endothelial
      cell damage, endovasculitis and fibromyxoid intimal change im arteries and veins,
      and interstitial pneumonitis with fibrosis.

PMID- 1985074
TI  - Neuromuscular manifestations of L-tryptophan-associated eosinophilia-myalgia
      syndrome: a histomorphologic analysis of 14 patients.
AB  - The recent delineation of a clinical syndrome marked by eosinophilia, myalgia,
      and scleroderma-like skin changes associated with L-tryptophan use has
      necessitated the Centers for Disease Control to initiate a health alert. The
      likely association of L-tryptophan ingestion with a syndrome that mimics
      eosinophilic fasciitis (Shulman's syndrome) further identifies an environmental
      agent associated with an inflammatory sclerosing rheumatic disease process. In
      this report, we present the clinical, morphologic, and enzyme histochemical
      findings in muscle, skin, and fascia biopsies from 14 cases fulfilling the Center
      for Disease Control diagnostic criteria for L-tryptophan-associated eosinophilia
      myalgia syndrome. The clinical syndrome reveals a high incidence of arthralgia,
      elbow contracture, and clinical neuropathy. The absence of significant change in
      creatine kinase or sedimentation rate allows for diagnostic separation from other
      inflammatory myopathies. Histoenzymatic features in muscle biopsies reveal a
      preferential epimysial-perimysial noneosinophilic infiltration characterized by
      acid phosphatase reactive histiocytosis, nonnecrotizing venulitis, perineural
      inflammation within dermis and perimysium, type II fiber atrophy with
      superimposed denervation features, and perifascicular alkaline phosphatase
      reactivity representing early neofibroplasia. The constellation of changes in
      skin, fascia, and muscle, with the defined clinical syndrome, allows for accurate
      differentiation from allied syndromes, including eosinophilic polymyositis,
      scleroderma, idiopathic polymyositis/dermatomyositis, polyarteritis nodosa, and
      toxic oil syndrome. Accurate differentiation from eosinophilic fasciitis still
      rests on a history of L-tryptophan ingestion.

PMID- 1985075
TI  - Ultrastructural and immunohistochemical segregation of gemistocytic subsets.
AB  - Gemistocytes are frequently encountered in cases of reactive gliosis as well as
      in glial tumors. Recently, miniature forms of gemistocytes (minigemistocytes)
      were recognized as cellular constituents of oligodendrogliomas. Antibodies
      specific for the intermediate filaments glial fibrillary acidic protein and
      vimentin are reactive with gemistocytic cells, but do not react specifically with
      these cells. In a study of 23 glial tumors we found the monoclonal antibody Pm43
      selectively reactive with the classical gemistocytes as well as with the
      minigemistocytes. Nevertheless, at the ultrastructural level a striking
      difference in the arrangement of the glial filaments between both gemistocytic
      cell types was found. Immunoelectron microscopy showed that the reactivity for
      the newly discovered gemistocytic marker Pm43 was confined to identical
      intermediate filaments. Despite immunohistochemical homology, a clearly different
      ultrastructure divides classic gemistocytes and minigemistocytes into two
      subsets.

PMID- 1985076
TI  - Chlamydia trachomatis in chronic abacterial prostatitis: demonstration by
      colorimetric in situ hybridization.
AB  - Twenty-three transurethral resected prostate specimens with histologic evidence
      of chronic abacterial prostatitis were evaluated by colorimetric in situ
      hybridization for evidence of Chlamydia trachomatis. Intracellular chlamydia
      bodies were detected in seven of 23 cases (30.4%). In five of seven positive
      cases, chlamydia inclusion bodies were present within both epithelial cells and
      intraluminal histiocytes. In two of seven positive cases, extracellular chlamydia
      bodies were identified in conjunction with intraepithelial inclusions. In only
      one case were extraductal, extraacinar, intrahistiocytic inclusion bodies
      observed. Our study confirms previous reports implicating C trachomatis as an
      etiologic agent in chronic abacterial prostatitis, and underscores the
      applicability of DNA probes for the detection and identification of C trachomatis
      in routinely fixed, paraffin-embedded tissues.

PMID- 1985077
TI  - Vasculo-Behcet's disease: a pathologic study of eight cases.
AB  - Behcet's disease associated with large vascular lesions is called vasculo
      Behcet's disease. The pathologic features of eight autopsy cases of vasculo
      Behcet's disease were studied. The patients' ages ranged from 31 to 56 years;
      there were five men and three women. Of these patients, large vascular lesions
      were as follows: aneurysm (three cases), aneurysm and arterial occlusion (one
      case), aneurysm with arterial and venous occlusion (one case), and venous
      occlusion (two cases). Aneurysms were of the saccular or dissecting type. The
      aneurysm formation most commonly occurred in the aorta (two cases).
      Histologically, aortitis was seen in six patients. Aortitis was divided into
      active and scar stages. In one case with active stage aortitis, granulomatous
      aortitis similar to Takayasu's arteritis was seen. In conclusion, we believe that
      the large arterial lesion in vasculo-Behcet's disease represents inflammation
      occurring in the media and adventitia. In the affected arteries, active arteritis
      occurs initially, followed by destruction of the media and fibrosis. Saccular
      aneurysms are probably produced by severe destruction of the media by intense
      active inflammation. The large venous lesions represent thrombophlebitis.

PMID- 1985078
TI  - The histologic spectrum of pigmented spindle cell nevus: a review of 120 cases
      with emphasis on atypical variants.
AB  - The histopathologic features of 120 cases of pigmented spindled nevus (PSCN) from
      the years 1973 through 1988 were reviewed from a consultative practice heavily
      weighted with difficult nevomelanocytic lesions. The patients' mean age was 25.2
      years, and females outnumbered males (68 versus 52). Extremity lesions made up
      69.6% of the total, with the thigh the most common site. The lesions were
      categorized into one of four variants of PSCN, based on the presence or absence
      of various architectural and cytologic parameters and involvement of the
      reticular dermis. Thirteen cases (10.8%) were designated typical PSCN, and were
      characterized by fascicles of uniform pigmented spindle cells without cellular
      atypia and limited to the epidermis or papillary dermis. Ninety-five cases
      (79.2%) were classified as atypical PSCN (PSCN with architectural and/or
      cytologic atypia). Some of the latter also demonstrated substantial numbers of
      epithelioid cells, thus exhibiting some overlap with Spitz nevus. Eight cases
      showed striking features of dysplastic nevus. Ten cases had fascicles of
      pigmented spindle cells involving the reticular dermis ("plexiform" PSCN). Two
      cases were designated as combined PSCN because of the presence of banal nevus
      cells in addition to the spindle cell component. Clinical follow-up of a small
      group of patients has not suggested, to date, any aggressive behavior. Knowledge
      of PSCN and its atypical variants is important for discrimination from malignant
      melanoma.

PMID- 1985079
TI  - Pseudomalignant ulcerative change of the gastrointestinal tract.
AB  - The occurrence of pseudomalignant ulcerative change in seven specimens from the
      colon and rectum of six patients is described. In all cases, there was surface
      ulceration of a polypoid lesion which contained granulation tissue and acute and
      chronic inflammation. There was an underlying inflammatory pseudopolyp in four
      lesions, a juvenile polyp in one lesion, an adenomatous polyp in one lesion, and
      a benign retention polyp in one lesion. Within the stroma of all cases were
      numerous atypical cells that mimicked a malignant neoplasm. The atypical cells
      expressed vimentin in immunohistochemical studies; no expression of keratins,
      leukocyte common antigen, factor VIII, Ulex europaeus, carcinoembryonic antigen,
      actin, or desmin was found. Recognition of this lesion is important, as confusion
      with carcinoma, lymphoma, sarcoma, or a viral infection may easily occur.

PMID- 1985080
TI  - Mycoplasma fermentans (incognitus strain) infection in the kidneys of patients
      with acquired immunodeficiency syndrome and associated nephropathy: a light
      microscopic, immunohistochemical, and ultrastructural study.
AB  - We studied renal tissues from 203 patients with acquired immunodeficiency
      syndrome (AIDS). Of the 203 patients, 20 showed light-microscopic changes
      characteristic of AIDS-associated nephropathy (AAN). Fifteen of the 20 (group A)
      were examined by immunohistochemistry using Mycoplasma fermentans (incognitus
      strain)-specific monoclonal antibodies and electron microscopy. Renal tissues
      from all 15 AAN patients showed positive staining for the incognitus strain
      mycoplasmal antigens within glomerular endothelial and epithelial cells,
      glomerular basement membrane, tubular epithelial cells and casts, and mononuclear
      interstitial cells. Ultrastructural study of these 15 cases revealed mycoplasma
      like structures in various locations including glomerular epithelial and
      endothelial cells, glomerular basement membrane, tubular epithelial cells and
      casts, and mononuclear interstitial cells. In a parallel study, renal tissues
      from 15 patients with AIDS with essentially normal renal histology or mild
      interstitial mononuclear cell infiltration (group B) were also examined. These
      tissues showed no evidence of incognitus strain mycoplasmal infection in renal
      parenchymal cells; however, occasional scattered mononuclear interstitial cells
      were positive for the antigens of this organism. Renal tissues from five patients
      dying with non-AIDS diseases (group C) showed no staining for the incognitus
      strain antigens in any location. Therefore, infection of renal parenchymal cells
      by M fermentans (incognitus strain) in the kidneys of AIDS patients is apparently
      associated with AAN.

PMID- 1985081
TI  - Flat adenomas of the colon.
AB  - Twenty-nine flat adenomas of the colon from 18 patients were identified by
      histologic review of 340 surgically or colonoscopically removed adenomas from 210
      patients. All lesions had a radial diameter of 1.0 cm or less. Twelve of 29 flat
      adenomas (41%) contained high-grade epithelial dysplasia, while only five of 127
      polypoid tubular adenomas 1.0 cm in diameter or less (4%) contained high-grade
      epithelial dysplasia. Nine patients had multiple flat adenomas, and two patients
      had concurrent flat, ulcerated colonic carcinomas without an identifiable
      polypoid precursor adenoma. Colonoscopically and grossly, the lesions were
      described as sessile or flat, slightly raised plaques, which might be easily
      missed on colonoscopic examination. These findings suggest that flat adenomas may
      be a subtype of colonic adenomas with a propensity for development of high-grade
      epithelial dysplasia at a small size. These lesions may be precursors of small,
      flat, ulcerated colonic carcinomas. Heightened colonoscopic surveillance of
      patients in whom flat adenomas have been identified may be warranted.

PMID- 1985082
TI  - Glycogen-rich clear-cell carcinoma of the breast: a clinicopathologic and flow
      cytometric study.
AB  - Six glycogen-rich clear-cell carcinomas (GCC) were found among 439 cases of
      breast cancer (BC) in a thorough search among a defined urban population. Five of
      these six patients had axillary lymph node metastases at diagnosis and all five
      died from their breast cancer within 7 years following the diagnosis. Tumors with
      histologic features of GCC were larger (P = 0.03), and they had a large DNA index
      (greater than 1.3) in flow cytometric DNA analysis more frequently than BCs in
      general (P = 0.04). All GCCs were nondiploid and had a high S-phase fraction
      (greater than 9%, mean 19.2%), which suggests that BCs with glycogen-rich cell
      features may be more aggressive than BCs in general.

PMID- 1985083
TI  - Hemangiopericytoma of the central nervous system: a review of 94 cases.
AB  - Ninety-four cases of central nervous system hemangiopericytoma (CNS-HPC) are
      reported. Hemangiopericytoma was found more commonly in men than in women. The
      mean age at diagnosis was 40.9 years for men and 47 years for women. The tumor
      was found throughout the entire CNS, usually superficially and closely related to
      the meninges. Based on multiple histologic variables, the original tumors were
      divided into differentiated (n = 67) and anaplastic (n = 27). Anaplastic HPC was
      characterized by the presence of necrosis and/or greater than five mitoses per
      ten 400x microscopic fields, and at least two of the following microscopic
      features: hemorrhage, moderate to high nuclear atypia, and moderate to high
      cellularity. For those patients known to be dead, median survival time was 144
      months for differentiated HPC and 62 months for anaplastic HPC. Fifty-seven
      (60.6%) patients had one or more recurrences and metastasis developed in 22
      (23.4%). Thirty-five of 56 patients with differentiated HPC had recurrence, while
      22 of 26 patients with anaplastic HPC had recurrence. Bone, liver, lung, central
      nervous system, and abdominal cavity were the most common sites of metastasis.
      Postoperative radiotherapy and/or chemotherapy were significantly associated with
      increased patient survival time.

PMID- 1985084
TI  - Miliary tuberculosis presenting as fever and jaundice with hepatic failure.
AB  - A 58-year-old male patient with miliary tuberculosis presenting as jaundice and
      hepatic dysfunction was reported. He was admitted to the Miyazaki Medical College
      Hospital, Miyazaki, Japan, because of fever and jaundice. Chest x-ray revealed a
      calcified primary affect of tuberculosis in the left upper lung field and miliary
      shadows throughout both lung fields. Liver function tests showed indications of
      obstructive jaundice and hepatic dysfunction. He rapidly deteriorated and died 3
      days after admission. Autopsy revealed disseminated miliary tuberculosis in all
      major organs. Many miliary tubercles were densely distributed in the liver,
      especially in and near the portal tracts. The intestine was free from tuberculous
      lesions. Miliary tuberculosis with jaundice is rare and its pathogenesis is
      discussed.

PMID- 1985085
TI  - Mediastinal ependymoma.
AB  - A mediastinal ependymoma in a 35-year-old Caucasian woman is reported. The tumor
      was located in a paravertebral posterior mediastinal location. No continuity with
      the spinal canal or with the lung was identified. The diagnosis was confirmed by
      immunoperoxidase staining for glial fibrillary protein and by the presence of
      cilia within intracytoplasmic vacuoles. To the best of our knowledge, this is the
      second reported case of ependymoma in this location.

PMID- 1985086
TI  - Percutaneous transluminal coronary angioplasty guidewire-induced coronary artery
      dissection without balloon inflation.
AB  - A case of arterial dissection of the right coronary artery secondary to
      angioplasty guidewire manipulation is presented. No balloon inflation was
      performed. The histologic appearance of the involved arterial segment was similar
      to that found in the left anterior descending coronary artery, which had
      undergone successful balloon dilatation. Both arteries demonstrated medial
      disruption and fibrointimal proliferation. The pathologic features of angioplasty
      induced vascular injury may occur with or without balloon inflation.

PMID- 1985087
TI  - Integrins.

PMID- 1985088
TI  - A mathematical model of the volume, pH, and ion content regulation in
      reticulocytes. Application to the pathophysiology of sickle cell dehydration.
AB  - We developed a mathematical model of the reticulocyte, seeking to explain how a
      cell with similar volume but much higher ionic traffic than the mature red cell
      (RBC) regulates its volume, pH, and ion content in physiological and abnormal
      conditions. Analysis of the fluxbalance required by reticulocytes to conserve
      volume and composition predicted the existence of previously unsuspected Na(+)
      dependent Cl- entry mechanisms. Unlike mature RBCs, reticulocytes did not tend to
      return to their original state after brief perturbations. The model predicted
      hysteresis and drift in cell pH, volume, and ion contents after transient
      alterations in membrane permeability or medium composition; irreversible cell
      dehydration could thus occur by brief K+ permeabilization, transient medium
      acidification, or the replacement of external Na+ with an impermeant cation. Both
      the hysteresis and drift after perturbations were shown to depend on the pHi
      dependence of the K:Cl cotransport, a major reticulocyte transporter. This
      behavior suggested a novel mechanism for the generation of irreversibly sickled
      cells directly from reticulocytes, rather than in a stepwise, progressive manner
      from discocytes. Experimental tests of the model's predictions and the hypothesis
      are described in the following paper.

PMID- 1985089
TI  - Effect of sodium chloride gradients on water flux in rat descending vasa recta.
AB  - In the hydropenic kidney, volume efflux from descending vasa recta (DVR) occurs
      despite an intracapillary oncotic pressure that exceeds hydraulic pressure. That
      finding has been attributed to small solute gradients which may provide an
      additional osmotic driving force favoring water transport from DVR plasma to the
      papillary interstitium. To test this hypothesis, axial gradients of NaCl and urea
      in the papilla were eliminated by administration of furosemide and saline. DVR
      were then blocked with paraffin and microperfused at 10 nl/min with a buffer
      containing albumin, fluorescein isothiocyanate labeled dextran (FITC-Dx), 22Na,
      and NaCl in a concentration of 0 (hypotonic to the interstitium), 161 (isotonic)
      or 322 mM (hypertonic). Collectate was obtained from the perfused DVR by
      micropuncture and the collectate-to-perfusate ratios of FITC-Dx and 22Na were
      measured. A mathematical model was employed to determine DVR permeability (Ps)
      and reflection coefficient to NaCl (sigma NaCl). The rate of transport of water
      from the DVR lumen to the papillary interstitium was 2.8 +/- 0.3 (Nv = 22), -0.19
      +/- 0.4 (Nv = 15), and -2.3 +/- 0.3 nl/min (Nv = 21) (mean +/- SE) when perfusate
      NaCl was 0, 161, or 322 mM, respectively (Nv = number of DVR perfused). The
      collectate-to-perfusate 22Na concentration ratios were 0.34 +/- 0.04, 0.36 +/-
      0.04 and 0.37 +/- 0.03 for those groups, respectively. Based on these data, Ps is
      calculated to be 60.4 x 10(-5) +/- 4.0 x 10(-5) cm/s and sigma NaCl less than
      0.05. The results of this study confirm that transcapillary NaCl concentrations
      gradients induce water movement across the wall of the DVR.

PMID- 1985090
TI  - Functional relationship of thyroid hormone-induced lipogenesis, lipolysis, and
      thermogenesis in the rat.
AB  - Metabolic balance studies were carried out to determine the interrelationships of
      thyroid hormone-induced lipogenesis, lipolysis, and energy balance in the free
      living rat. Intraperitoneal doses of 15 micrograms triiodothyronine (T3)/100 g
      body wt per d caused an increase in caloric intake from 26.5 +/- 1.7 (mean +/-
      SEM) kcal/100 g per d to 38.1 +/- 1.5 kcal/100 g per d. Food intake, however,
      rose only after 4-6 d of treatment and was maximal by the 8th day. In contrast,
      total body basal oxygen consumption rose by 24 h and reached a maximum by 4 d.
      Since total urinary nitrogen excretion and hepatic phosphoenolpyruvate
      carboxykinase mRNA did not rise, gluconeogenesis from protein sources did not
      supply the needed substrate for the early increase in calorigenesis. Total body
      fat stores fell approximately 50% by the 6th day of treatment and could account
      for the entire increase in caloric expenditure during the initial period of T3
      treatment. Total body lipogenesis increased within 1 d and reached a plateau 4-5
      d after the start of T3 treatment. 15-19% of the increased caloric intake was
      channeled through lipogenesis, assuming glucose to be the sole substrate for
      lipogenesis. The metabolic cost of the increased lipogenesis, however, accounted
      for only 3-4% of the T3-induced increase in calorigenesis. These results suggest
      that fatty acids derived from adipose tissue are the primary source of substrate
      for thyroid hormone-induced calorigenesis and that the early increase in
      lipogenesis serves simply to maintain fat stores. Since the mRNAs coding for
      lipogenic enzymes rise many hours before oxygen consumption and lipolysis, these
      results suggest that T3 acts at least in part by an early coordinate induction of
      the genes responsible for these processes.

PMID- 1985091
TI  - Rapid expression of heat shock protein in the rabbit after brief cardiac
      ischemia.
AB  - The effect of brief myocardial ischemia on the expression of heat shock protein
      (HSP 70) was examined in an in vivo rabbit model of myocardial ischemia using
      Northern blotting. Functional studies were carried out in the open-chested
      anesthetized rabbit. The large marginal branch of the left circumflex was
      occluded four times for 5 min. Using piezoelectric crystals implanted midwall in
      the ischemic zone, end-diastolic length, end-systolic length, and percent
      segmental shortening were assessed. Expression of HSP 70 was measured by Northern
      blotting. A single 5-min coronary occlusion doubled the expression of HSP 70
      whereas four cycles of 5 min of ischemia/5 min of reperfusion resulted in a
      threefold increase in HSP 70 mRNA (P less than 0.001). Measurements with the
      piezoelectric crystals showed mild myocardial dysfunction concomitant with the
      increase in HSP 70. This increase in HSP 70 mRNA after repetitive brief ischemia
      was transient, occurring as early as 1 h and returning to baseline by 24 h after
      ischemia. Western blot analysis with a monoclonal antibody to HSP 70 was used to
      compare sham and postischemic myocardial HSP 70 levels. Changes in the amount of
      HSP 70 were evident as early as 2 h and were even more striking at 24 h.

PMID- 1985092
TI  - Loss of endothelium-dependent relaxant activity in the pulmonary circulation of
      rats exposed to chronic hypoxia.
AB  - To determine whether exposure to chronic hypoxia and subsequent development of
      pulmonary hypertension induces alterations of endothelium-dependent relaxation in
      rat pulmonary vascular bed, we studied isolated lung preparations from rats
      exposed to either room air (controls) or hypoxia (H) during 1 wk (1W-H), 3 wk (3W
      H), or 3W-H followed by 48 h recovery to room air (3WH + R). In lungs pretreated
      with meclofenamate (3 microM), the endothelium-dependent vasodilator responses to
      acetylcholine (10(-9)-10(-6) M) and ionophore A23187 (10(-9)-10(-7) M) were
      examined during conditions of increased tone by U46619 (50 pmol/min).
      Acetylcholine or A23187 produced dose-dependent vasodilation in control lungs,
      this response was reduced in group 1W-H (P less than 0.02), abolished in group 3W
      H (P less than 0.001), and restored in group 3WH + R. In contrast, the
      endothelium-independent vasodilator agent sodium nitroprusside remained fully
      active in group 3W-H. The pressor response to 300 pM endothelin was greater in
      group 3W-H than in controls (6.8 +/- 0.5 mmHg vs. 1.6 +/- 0.2 mmHg, P less than
      0.001) but was not potentiated by the endothelium-dependent relaxing factor
      (EDRF) antagonists: hydroquinone (10(-4) M); methylene blue (10(-4) M); and
      pyrogallol (3 x 10(-5) M) as it was in controls. It was similar to controls in
      group 3W-H + R. Our results demonstrate that hypoxia-induced pulmonary
      hypertension is associated with a loss of EDRF activity in pulmonary vessels,
      with a rapid recovery on return to a normoxic environment.

PMID- 1985093
TI  - Purification and characterization of a major human Pneumocystis carinii surface
      antigen.
AB  - Previous studies of Pneumocystis carinii have identified the major surface
      antigen of rat and human isolates as proteins of 116,000 and 95,000 mol wt,
      respectively, that are antigenically not identical. In this study both rat and
      human P. carinii proteins were purified by solubilization with zymolyase followed
      by molecular sieve and ion exchange chromatography. The native proteins had an
      apparent mol wt of 290,000 or greater, based on molecular sieve studies as well
      as cross-linking studies. Both proteins were glycoproteins; treatment with
      endoglycosidase H resulted in a 9% decrease in mol wt. The carbohydrate
      composition of the rat P. carinii glycoprotein was distinct from the human
      isolate; glucose, mannose, galactose, and glucosamine occurred in approximately
      equimolar ratios in the human P. carinii protein, whereas glucose and mannose
      were the predominant sugars of the rat P. carinii protein. To evaluate humoral
      immune responses to the human P. carinii protein, an enzyme-linked immunosorbent
      assay using purified protein was developed. Some, but not all, patients who
      subsequently developed P. carinii pneumonia demonstrated a serum antibody
      response to the surface antigen. Nearly all subjects without a history of P.
      carinii pneumonia had no detectable antibodies. Purified P. carinii proteins will
      greatly facilitate the investigation of host-P. carinii interactions.

PMID- 1985095
TI  - Regulation of forearm lipolysis in different types of obesity. In vivo evidence
      for adipocyte heterogeneity.
AB  - Forearm and systemic adipose tissue free fatty acid (FFA) release was measured in
      eight nonobese, six lower-body obese, and eight upper-body obese women under
      basal, hyperinsulinemic, and hypoinsulinemic conditions to determine whether
      forearm fat is regulated in a similar manner as whole body fat. RESULTS: Adipose
      tissue palmitate release was greater from forearm than whole body (5.97 +/- 0.75
      vs. 3.84 +/- 0.34 mumol.kg fat-1.min-1, respectively, P less than 0.005, n = 22
      subjects). Systemic palmitate release, relative to fat mass, was significantly (P
      less than 0.01) greater in nonobese than upper-body obese, and upper-body obese
      than lower-body obese women, and forearm adipose tissue palmitate release
      followed the same pattern. Hyperinsulinemia suppressed systemic and forearm
      lipolysis to similar degrees, however, hypoinsulinemia consistently increased
      systemic palmitate flux without increasing forearm palmitate release. These
      results confirm the heterogeneity of adipose tissue in an in vivo model and
      emphasize the need to consider which adipose tissue depots are responsible for
      the differences in systemic FFA flux in obese and nonobese humans.

PMID- 1985094
TI  - Protein heterogeneity in the human Ro/SSA ribonucleoproteins. The 52- and 60-kD
      Ro/SSA autoantigens are encoded by separate genes.
AB  - Two cDNA clones encoding the 52-kD form of a protein present in human Ro/SSA
      ribonucleoprotein complexes were cloned from a lambda gt11 human thymocyte cDNA
      library. These clones reacted with lupus patient sera which had anti-52-kD Ro/SSA
      antibodies, and with affinity-purified anti-52-kD Ro/SSA antibodies. Moreover,
      affinity-purified antibodies isolated from isopropyl-beta-D-thiogalactopyranoside
      induced proteins of these clones reacted only with the 52-kD protein of
      lymphocytes in Western blots and precipitated Ro/SSA hY RNAs, confirming that the
      clones encode a 52-kD Ro/SSA antigen. The cDNA contains a single open reading
      frame of 1,425 nucleotides and encodes a predicted 475-amino acid polypeptide
      with a molecular mass of 54,108 D. This protein appears unique in that both a
      zinc finger and leucine zipper motif are present on this protein. Surprisingly,
      no homology was found between the 52-kD Ro/SSA gene or protein and three
      published 60-kD Ro/SSA sequences. However, significant similarity of the 52-kD
      Ro/SSA was detected with human rfp and mouse rpt-1. These three proteins each
      contain similar zinc finger motifs in approximately their first 145 amino acid
      residues. The cDNA and the protein expressed therefrom are useful in the analysis
      of the structural and functional properties of this autoantigen.

PMID- 1985097
TI  - Intracellular regulation of the production and release of human erythroid
      directed lymphokines.
AB  - Erythroid burst-promoting activity (BPA) is released from B lymphocytes in
      soluble (sBPA) and membrane-bound (mBPA) forms. To study intracellular processes
      involved in production of these physically separable factors, we measured their
      time course release into serum-free medium from B cells that were pulse-exposed
      for 5-240 min to nonmitogenic base medium or inhibitors of energy-dependent
      metabolism (2,4-dinitrophenol, sodium azide, and 2-deoxy-D-glucose),
      transcription and translation (actinomycin D and cycloheximide), replicative DNA
      synthesis (cytosine arabinoside), or posttranslational processing (monensin).
      mBPA and sBPA were initially detectable after 1 and 2 h, respectively. Maximum
      cumulative levels of 8 +/- 0.6 and 9 +/- 1.0 U/ml, respectively, were reached
      after 8 h. In contrast, cumulative mBPA and sBPA levels in medium prepared from
      cells treated with metabolic inhibitors were reduced by up to 90%. Both surface
      exfoliation and mBPA expression by intact plasma membranes were diminished.
      Whereas pulse-exposure to cytosine arabinoside had no effect, treatment with
      actinomycin D or cycloheximide abolished BPA expression. Exposure to monensin
      reduced mBPA and sBPA levels to zero in a concentration-and time-dependent
      fashion. We conclude that production and release of BPA is an energy-dependent
      process, requiring mRNA synthesis and translation and posttranslational
      remodeling of the protein but not replicative DNA synthesis.

PMID- 1985096
TI  - Apolipoprotein (apo) E inhibits the capacity of monosodium urate crystals to
      stimulate neutrophils. Characterization of intraarticular apo E and demonstration
      of apo E binding to urate crystals in vivo.
AB  - Factors that modulate the ability of monosodium urate crystals to stimulate
      leukocytes could regulate gouty inflammation. Lipoproteins that bear apo B-100
      and apo E bind to urate crystals and suppress crystal-neutrophil interaction. In
      this study, we observed that urate crystals, coated with apo E of monocyte
      origin, had a diminished ability to stimulate neutrophils. Apo E was also
      detected on the surface of urate crystals recovered from gout patients. Thus, we
      analyzed apo E in noninflammatory synovial fluid, and found it to be associated
      with particles of heterogeneous size and of predominantly alpha and pre-beta
      electrophoretic mobility. Local articular synthesis of at least a portion of
      synovial fluid apo E was suggested because (a) the synovial fluid/plasma
      concentration ratio of apo E was significantly higher than that for both apo B
      and apo A-I, which are not widely synthesized by extrahepatic tissues, (b)
      cultured rheumatoid synovial cells in first passage secreted apo E, (c) a portion
      of synovial fluid apo E was heavily sialylated. We conclude that synovial fluids
      contain apo E that appears partly of local origin. Apo E binds to urate crystals
      and could modulate gouty inflammation.

PMID- 1985098
TI  - Importance of mitral subvalvular apparatus in terms of cardiac energetics and
      systolic mechanics in the ejecting canine heart.
AB  - To assess the importance of the intact mitral subvalvular apparatus for left
      ventricular (LV) energetics, data from nine open-chest ejecting canine hearts
      were analyzed using piezoelectric crystals to measure LV volume. After mitral
      valve replacement with preservation of all chordae tendineae, baseline LV
      function was assessed during transient caval occlusion: A quadratic fit of the LV
      end-systolic pressure-volume data was used to determine the curvilinear end
      systolic pressure-volume relationship (ESPVR). All chordae were then divided with
      exteriorized snares. Reassessment revealed deterioration of global LV pump
      function: (a) the coefficient of nonlinearity, decreased (less negative) by 90%
      (P = 0.06); (b) slope of the curvilinear ESPVR at the volume axis intercept,
      decreased by 75% (P = 0.01); and V100, end-systolic volume at 100 mmHg end
      systolic pressure, increased by 42% (P less than 0.02). Similarly, preload
      recruitable stroke work fell significantly (-14%) and Vw1,000 (end-diastolic
      volume [EDV] at stroke work [SW] of 1,000 mmHg.ml) rose by 17% (P less than
      0.04). With respect to LV energetics, the total mechanical energy generated by
      the ventricle decreased, as indicated by a decline in the slope of the pressure
      volume area (PVA)-EDV relationship (120 +/- 13 [mean +/- SD] vs. 105 +/- 13 mmHg,
      P less than 0.001). Additionally, comparison of LV SW and PVA from single beats
      with matched EDV showed that the efficiency of converting mechanical energy to
      external work (SW/PVA) declined by 14% (0.65 +/- 0.13 vs. 0.56 +/- 0.08, P less
      than 0.03) after chordal division. While effective systemic arterial elastance,
      Ea, also fell significantly (P = 0.03) after the chordae were severed, the Ea/Ees
      ratio (Ees = slope of the linear ESPVR) increased by 124% (0.91 +/- 0.53 vs. 2.04
      +/- 0.87, P = 0.001) due to a proportionally greater decline in Ees. This
      indicates a mismatch in ventriculo-arterial interaction, deviating from that
      required for maximal external output (viz., Ea/Ees = 1). These adverse effects of
      chordal division may be related to the observed changes in LV geometry (i.e.,
      eccentricity). We conclude that the intact mitral subvalvular apparatus is
      important in optimizing LV energetics and ventriculo-vascular coupling in
      addition to the enhancement of LV systolic performance.

PMID- 1985099
TI  - On the mechanism of impaired insulin secretion in chronic renal failure.
AB  - It has been suggested that a sustained rise in resting levels of cytosolic
      calcium [Ca2+]i of pancreatic islets is responsible for impaired insulin
      secretion in chronic renal failure (CRF). Evidence for such an event is lacking
      and the mechanisms through which it may affect insulin secretion are not known.
      Studies were conducted in normal, CRF, and normocalcemic, parathyroidectomized
      (PTX) CRF rats to answer these questions. Resting levels of [Ca2+]i of islets
      from CRF rats were higher (P less than 0.01) than in control of CRF-PTX rats.
      [3H]2-deoxyglucose uptake and cAMP production by islets were not different in the
      three groups. Insulin content of, and glucose-induced insulin secretion by islets
      from CRF rats was lower (P less than 0.01) than in control and CRF-PTX rats. In
      contrast, glyceraldehyde-induced insulin release by CRF islets was normal. Basal
      ATP content, both glucose-stimulated ATP content and ATP/ADP ratio, net lactic
      acid output, Vmax of phosphofructokinase-1, and Ca2+ ATPase of islets from CRF
      rats were lower (P less than 0.02-less than 0.01) than in normal or CRF-PTX
      animals. Data show that: (a) Glucose but not glyceraldehyde-induced insulin
      secretion is impaired in CRF; (b) the impairment in glucose-induced insulin
      release in CRF is due to a defect in the metabolism of glucose; (c) this latter
      defect is due to reduced ATP content induced partly by high [Ca2+]i of islets;
      and (d) the high [Ca2+]i in islets of CRF rats is due to augmented PTH-induced
      calcium entry into cells and decreased calcium extrusion from the islets
      secondary to reduced activity of the Ca2+ ATPase.

PMID- 1985100
TI  - Obesity and the metabolic response to severe multiple trauma in man.
AB  - In the obese state profound metabolic disturbances exist and it is not known how
      this disrupted metabolism in obese subjects (body mass index greater than 30) may
      change their ability to respond to the superimposed, injury-induced stress.
      Understanding the mechanisms that modify the metabolic parameters in traumatized
      obese patients is essential in their nutritional assessment and further
      treatment. We have investigated in 7 obese and 10 nonobese multiple trauma
      patients, on a whole-body level, the energy metabolism, protein kinetics, and
      lipolysis in the early catabolic "flow phase" of severe injury when they were
      receiving maintenance fluids without calories or nitrogen. Traumatized obese
      patients mobilized relatively more protein and less fat compared with nonobese
      subjects. A relative block both in lipolysis and fat oxidation is experienced by
      injured obese patients that results in a shift to preferential use of proteins
      and carbohydrates. Reduced endogenous protein synthetic efficiency observed in
      obese patients implies increased protein recycling. Thus obese patients could not
      effectively use their most abundant fat fuel sources and have to depend on other
      fuel sources. The nutritional management of obese trauma victims should therefore
      be tailored towards provision of enough glucose calories to spare protein.

PMID- 1985101
TI  - Latent HIV-1 infection in enriched populations of blood monocytes and T cells
      from seropositive patients.
AB  - The extent of latent HIV-1 infection in blood T cells and monocytes of 23
      seropositive individuals was examined using DNA amplification (PCR) of HIV-1
      sequences. Amplified DNA was found in at least one cell type in all seropositives
      tested, including 13 asymptomatic, 5 ARC, and 5 AIDS patients. Amplification with
      two or more primer sets from the gag, env, LTR occurred in 21 (91%) patients' T
      cells and 17 (74%) patients' monocytes. However, amplification with the LTR
      primers in monocytes was uncommon. Among four patients tested, amplified DNA
      continued to be detected after a greater than one thousand-fold dilution (less
      than 500 cells) of both T cell and monocyte lysates. Repeat analysis after 7-9 mo
      in five seropositives yielded similar findings in T cells and monocytes, but some
      variation in the efficacy of amplification with individual primers occurred.
      There was no difference in those 10 patients who were taking AZT, compared to
      those who were untreated. Our results indicate that a fraction (less than 1%) of
      both T cells and monocytes in blood carry a latent infection in all stages of HIV
      1 disease and can serve as reservoirs throughout AZT therapy.

PMID- 1985102
TI  - The growth inhibition of human breast cancer cells by a novel synthetic progestin
      involves the induction of transforming growth factor beta.
AB  - Recent experimental work has identified a novel intracellular binding site for
      the synthetic progestin, Gestodene, that appears to be uniquely expressed in
      human breast cancer cells. Gestodene is shown here to inhibit the growth of human
      breast cancer cells in a dose-dependent fashion, but has no effect on endocrine
      responsive human endometrial cancer cells. Gestodene induced a 90-fold increase
      in the secretion of transforming growth factor-beta (TGF-beta) by T47D human
      breast cancer cells. Other synthetic progestins had no effect, indicating that
      this induction is mediated by the novel Gestodene binding site and not by the
      conventional progesterone receptor. Furthermore, in four breast cancer cell
      lines, the extent of induction of TGF-beta correlated with intracellular levels
      of Gestodene binding site. No induction of TGF-beta was observed with the
      endometrial cancer line, HECl-B, which lacks the Gestodene binding site, but
      which expresses high levels of progesterone receptor. The inhibition of growth of
      T47D cells by Gestodene is partly reversible by a polyclonal antiserum to TGF
      beta. These data indicate that the growth-inhibitory action of Gestodene may be
      mediated in part by an autocrine induction of TGF-beta.

PMID- 1985103
TI  - Diacylglycerol accumulation and microvascular abnormalities induced by elevated
      glucose levels.
AB  - The present experiments were undertaken to examine the hypothesis that glucose
      induced increased de novo synthesis of 1,2-diacyl-sn-glycerol (which has been
      observed in a number of different tissues, including retinal capillary
      endothelial cells exposed to elevated glucose levels in vitro) and associated
      activation of protein kinase C may play a role in mediating glucose-induced
      vascular functional changes. We report here that twice daily instillation of 30
      mM glucose over 10 d in a rat skin chamber granulation tissue model induces
      approximately a 2.7-fold increase in diacylglycerol (DAG) levels (versus tissues
      exposed to 5 mM glucose) in association with marked increases in vascular
      clearance of albumin and blood flow. The glucose-induced increase in DAG levels
      as well as the vascular functional changes are prevented by addition of 3 mM
      pyruvate. Pharmacological activation of protein kinase C with the phorbol ester
      TPA in the presence of 5 mM glucose increases microvascular albumin clearance and
      blood flow, and similar effects are observed with 1-monoolein (MOG), a
      pharmacological inhibitor of the catabolism of endogenous DAG. A pharmacological
      inhibitor of protein kinase C (staurosporine) greatly attenuates the rise in
      microvascular albumin clearance (but not the rise in blood flow) induced by
      glucose or by MOG. These findings are compatible with the hypothesis that
      elevated concentrations of glucose increase tissue DAG content via de novo
      synthesis, resulting in protein kinase C activation, and that these biochemical
      events are among the factors that generate the increased microvascular albumin
      clearance.

PMID- 1985104
TI  - Decidua produces a protein that inhibits choriogonadotrophin release from human
      trophoblasts.
AB  - To test the hypothesis that uterine decidua may modulate trophoblast function,
      trophoblasts and decidual cells were isolated from term placentas by enzymatic
      digestion and Percoll gradient centrifugation. Placental trophoblasts were
      cocultured with decidual cells and trophoblasts or JEG-3 choriocarcinoma cells
      were incubated with medium conditioned by decidual cells (DCM) for 72-96 h. In
      cocultures decidual cells inhibited choriogonadotropin (hCG) release from
      trophoblasts by 75% in comparison with controls (P less than 0.001). The DCM
      contained a factor that markedly inhibited hCG release from trophoblasts and JEG
      cells in vitro compared with controls. The inhibitory effect of the factor on hCG
      release was dose dependent, and could be eliminated by boiling the DCM for 30 min
      or proteolytic enzyme treatment. Ultrafiltration and Sephadex G-50 fractionation
      of the DCM indicated that the apparent molecular mass was 7,000-10,000 D. DCM
      also inhibited the stimulatory effect of exogenous cAMP on hCG secretion by JEG-3
      cells, suggesting that DCM may interfere with activation of the cAMP-dependent
      protein kinases or transcription of hCG genes. These results suggest that the
      release of trophoblast hCG is under local paracrine control, regulated in part by
      a protein released by decidual cells.

PMID- 1985105
TI  - Evaluation of pathways for the cellular uptake of high density lipoprotein
      cholesterol esters in rabbits.
AB  - Cholesterol esters (CE) formed in HDL by lecithin:cholesterol acyltransferase are
      thought to mediate the return of cholesterol from extrahepatic tissues to the
      liver for excretion or reutilization. Several pathways may be involved in that
      process. Tracer kinetics were used to estimate the contributions of the various
      pathways to cellular uptake of HDL CE in rabbits. Tracers of HDL CE, HDL apo A-I,
      LDL apo B, and VLDL CE were simultaneously injected intravenously. Plasma decays
      were followed for 24 h in 4 lipoprotein pools: HDL without apo E, HDL with apo E,
      LDL, and VLDL. Kinetic analysis of the resulting plasma decay curves revealed
      that the preponderance of plasma CE (greater than 90%) originated in the HDL
      fraction. About 70% of HDL CE were cleared from plasma after transfer to LDL and
      VLDL, 20% were cleared directly from the HDL pool without HDL particle uptake
      ("selective" uptake), and 10% were cleared in HDL particles (including particles
      containing apo E). Since rabbits have about four times the plasma cholesterol
      ester transfer activity of man, and since the transfer pathway must compete with
      the selective uptake pathway, these results make it likely that selective uptake
      plays a substantial role in humans in the clearance of HDL CE.

PMID- 1985106
TI  - Insulin-like growth factor I gene expression in isolated rat renal collecting
      duct is stimulated by epidermal growth factor.
AB  - The renal collecting duct is a site of insulin-like growth factor I (IGF I)
      synthesis. Epidermal growth factor (EGF) is also synthesized within the kidney in
      the thick ascending limb of Henle's loop and the distal tubule. EGF has been
      shown to regulate IGF I expression in nonrenal tissues. To shed light upon a role
      of EGF in intrarenal regulation of IGF I gene expression, plasma membranes
      prepared from collecting ducts isolated from rat kidney and collecting ducts
      themselves were incubated in the presence and absence of recombinant human EGF
      (hEGF). hEGF enhanced phospholipase C activity in collecting duct plasma
      membranes establishing the potential for EGF signal transduction at this site.
      Inclusion of hEGF in suspensions of collecting ducts increased production of
      immunoreactive IGF I in a concentration-dependent manner. Production was
      stimulated significantly by addition of 10(-8) or 10(-6) M hEGF to suspensions
      for 2 h. Levels of IGF I mRNA in collecting ducts were increased 2.8-fold after
      incubation with 10(-6) M hEGF in vitro. Our findings demonstrate a direct action
      of hEGF to enhance collecting duct IGF I gene expression in vitro. Such
      enhancement is likely to reflect an effect of EGF to stimulate IGF I production
      in the collecting duct of the intact kidney. Since EGF is produced in kidney, our
      findings are consistent with intrarenal paracrine regulation of IGF I gene
      expression by EGF.

PMID- 1985107
TI  - Neutrophil nicotinamide adenine dinucleotide phosphate oxidase assembly.
      Translocation of p47-phox and p67-phox requires interaction between p47-phox and
      cytochrome b558.
AB  - Two of the cytosolic NADPH oxidase components, p47-phox and p67-phox, translocate
      to the plasma membrane in normal neutrophils stimulated with phorbol myristate
      acetate (PMA). We have now studied the translocation process in neutrophils of
      patients with chronic granulomatous disease (CGD), an inherited syndrome in which
      the oxidase system fails to produce superoxide due to lesions affecting any one
      of its four known components: the gp91-phox and p22-phox subunits of cytochrome
      b558 (the membrane-bound terminal electron transporter of the oxidase), p47-phox,
      and p67-phox. In contrast to normal cells, neither p47-phox nor p67-phox
      translocated to the membrane in PMA-stimulated CGD neutrophils which lack
      cytochrome b558. In one patient with a rare X-linked form of CGD caused by a Pro-
      --His substitution in gp91-phox, but whose neutrophils have normal levels of this
      mutant cytochrome b558, translocation was normal. In two patients with p47-phox
      deficiency, p67-phox failed to translocate, whereas p47-phox was detected in the
      particulate fraction of PMA-stimulated neutrophils from two patients deficient in
      p67-phox. Our data suggest that cytochrome b558 or a closely linked factor
      provides an essential membrane docking site for the cytosolic oxidase components
      and that it is p47-phox that mediates the assembly of these components on the
      membrane.

PMID- 1985108
TI  - Cartilage expression of a type II collagen mutation in an inherited form of
      osteoarthritis associated with a mild chondrodysplasia.
AB  - In a family who expressed severe dominantly inherited osteoarthritis, the
      underlying mutation was traced by genomic sequencing to a single base change
      which predicts an amino acid substitution of cysteine for arginine at residue 519
      of the triple-helical domain of the type II collagen molecule (Ala-Kokko, L., C.
      T. Baldwin, R. W. Moskowitz, and D. J. Prockop. 1990. Proc. Natl. Acad. Sci. USA.
      87:6565-6568). In the present study we examined whether this predicted protein
      phenotype was evident in articular cartilage obtained from an affected family
      member who underwent hip surgery. The cartilage collagen was solubilized by CNBr
      digestion. Cysteine residues were labeled by reduction and alkylation with 14C
      iodoacetate. Collagen CNBr-peptides were fractionated by ion exchange and reverse
      phase column chromatography. One peptide from the alpha 1(II) chain, alpha 1(II)
      CB8, was found to be radiolabeled. Tryptic peptides were prepared from it and
      identified by microsequence analysis. The results show that approximately one
      quarter of the alpha 1(II) chains present in the polymeric extracellular collagen
      of the patient's cartilage contained the Arg519-to-Cys substitution. The protein
      exhibited other abnormal properties including disulfide-bonded alpha 1(II)-dimers
      and signs of posttranslational overmodification. The premature cartilage failure
      and osteoarthritis are presumably a result of the abnormal type II collagen being
      expressed in the cartilage matrix.

PMID- 1985110
TI  - Anderson's disease: genetic exclusion of the apolipoprotein-B gene in two
      families.
AB  - Anderson's disease is a recessive disorder characterized by intestinal fat
      malabsorption, absence of postprandial chylomicrons, and reduced levels of
      cholesterol, triglycerides, and apoproteins B, AI, and C. We have studied two
      families with, respectively, three and two children with Anderson's disease.
      Intestinal apo-B and apo-AIV mRNAs from two Anderson's patients were normal in
      size but their concentration was decreased fivefold compared with controls. After
      DNA digestion with seven restriction enzymes, restriction fragment length
      polymorphisms of apo-B gene did not show conclusive information except for Xba1,
      which revealed a lack of cosegregation between the restriction fragment length
      polymorphism and the Anderson's phenotype. Linkage analysis was performed using
      the polymorphism of the apo-B gene 3'minisatellite. Genomic DNA from parents and
      children was amplified by polymerase chain reaction using oligonucleotide primers
      flanking the apo-B gene 3'hypervariable locus. In both families each child
      inherited different apo-B alleles from at least one parent. According to the
      recessive mode of transmission of the disease, our results are incompatible with
      the involvement of the apo-B gene. More likely a posttranslational defect or a
      mutation in another gene encoding a protein essential for lipoprotein assembly or
      secretion may be involved.

PMID- 1985109
TI  - Intracellular activation of digestive zymogens in rat pancreatic acini.
      Stimulation by high doses of cholecystokinin.
AB  - The mechanism by which digestive zymogens become activated during acute
      pancreatitis remains poorly understood. Given the ability for cholecystokinin
      (CCK) to induce pancreatitis in vivo, the effects of high dose CCK on
      preparations of isolated pancreatic acini were examined. Using an immunologic
      technique for the detection of zymogen activation, CCK was found to stimulate the
      conversion of procarboxypeptidase A1 to a 35-kD form having the same net charge
      and electrophoretic mobility as purified recombinant carboxypeptidase A1. This
      enhanced conversion was proportional to the dose of CCK (maximal at 100 nM), and
      time dependent. CCK also produced changes in the electrophoretic mobility of
      procarboxypeptidase B and chymotrypsinogen 2 immunoreactivity, consistent with
      activation of these zymogens. These events were detectable only within acinar
      cell pellets and not in the incubation medium, suggesting an intracellular site
      of conversion. The conversion of procarboxypeptidase A1 to its active form was
      inhibited by pretreatment with the weak base chloroquine (40 microM) and the
      protonophore monensin (10 microM). This conversion was also inhibited by
      pretreatment with the serine protease inhibitor benzamidine (10 mM) but not the
      cysteine protease inhibitor E64 (100 microM). The results suggest that high dose
      CCK stimulates the intracellular activation of digestive zymogens within isolated
      pancreatic acini. This event appears to require an acidic subcellular compartment
      and serine protease activity.

PMID- 1985111
TI  - Iron mediates production of a neutrophil chemoattractant by rat hepatocytes
      metabolizing ethanol.
AB  - Ethanol metabolism in hepatocytes is accompanied by release of a potent lipid
      chemoattractant for neutrophils. Production of the factor may initiate the
      inflammation associated with alcoholic hepatitis. In previous studies with a
      cytosol system from liver, production was blocked by iron chelators as well as by
      catalase and superoxide dismutase, suggesting the involvement of oxyradicals in
      formation of the chemoattractant. These studies have examined the role of iron in
      intact hepatocytes using cells from rats fed an iron-deficient diet, a control
      diet or a diet containing 3% carbonyl iron. The iron content averaged 1.4 nmol/mg
      protein in iron-deficient cells, 6.3 in controls and 135.3 in iron-loaded cells.
      Hepatocytes from all groups were established in primary culture and incubated
      with ethanol (10 mM); the medium was assayed for chemoattractant activity for
      human neutrophils. Cultures from chow-fed or iron-loaded animals produced
      chemoattractant as previously reported. By contrast, chemoattractant production
      was undetectable in the iron-deficient cultures. Addition of ferric citrate (10
      microM) restored chemoattractant production while increasing cellular iron in the
      deficient cells less than 50% (to 2.3 nmol/mg protein). Addition of
      desferrioxamine mesylate to cultures of iron-loaded cells ablated chemoattractant
      production. The data provide evidence for the importance of hepatocellular iron
      in production of this alcohol-related lipid chemoattractant and suggest that a
      small intracellular pool of "free" iron plays a critical role.

PMID- 1985112
TI  - Molecular definition and sequence motifs of the 52-kD component of human SS-A/Ro
      autoantigen.
AB  - Serum SS-A/Ro autoantibodies are commonly found in patients with Sjogren's
      syndrome, systemic lupus erythematosus, neonatal lupus, and subacute cutaneous
      lupus. Two proteins of 60 and 52 kD have been described as targets for these
      autoantibodies. To define the 52-kD component unambiguously, cDNA clones were
      isolated from human HepG2 and MOLT-4 cell cDNA libraries. The identity of cDNA
      was established by (a) the specificity of the antibody affinity purified from the
      recombinant protein, (b) the reactivity of the purified recombinant protein with
      prototype SS-A/Ro sera in immunoblot and ELISA, and (c) two-dimensional gel
      comigration of MOLT-4 cell 52-kD protein and the recombinant protein. A 1.9-kb
      cDNA encoded the complete 52-kD protein containing 475 amino acids (Mr 54,082).
      Putative zinc-finger domains and a leucine zipper motif were identified in the
      amino-terminal half of the 52-kD protein, implicating its possible association
      with DNA/RNA. Sequence homology detected between the 52-kD protein and human ret
      transforming protein, and mouse T cell gene expression down-regulatory protein
      rpt-1, may provide leads to the functional role of the 52-kD protein in addition
      to the possibility that these proteins might constitute members of a subfamily of
      finger proteins.

PMID- 1985113
TI  - Human bronchus and intestine express the same mucin gene.
AB  - The amino acid and sugar composition of mucins from various organs is similar but
      not identical. This could arise by one or more of the following: organ-specific
      processing of a single core protein, organ-specific splicing of a single mucin
      mRNA, or organ-specific expression of various mucin genes. To begin to
      investigate the source of this variability, we examined (a) immunological cross
      reactivity and (b) cDNA cross-hybridization, among several mucin-secreting organs
      of the human body. Peptide-directed antibodies raised against both
      nondeglycosylated (LS) and deglycosylated (HFB) intestinal mucin strongly stained
      mucous cells in the bronchial epithelium and submucosal glands, indicating
      homology between mucins of the bronchus and intestine at the peptide level. By
      screening a bronchus cDNA library with an intestinal mucin cDNA, SMUC-41, we
      isolated a bronchus mucin cDNA, HAM-1. This cDNA is 96% homologous to the first
      repeat of SMUC-41. HAM-1 hybridized to restriction fragments of human genomic DNA
      identical to those hybridizing to SMUC-41 on Southern blots. SMUC-41 also
      hybridized to polydisperse transcripts in the bronchus, cervix, gall bladder, and
      mammary gland, indicating mucin homology among all these organs at the RNA level.
      We conclude that the bronchus and intestine express a common mucin gene, which is
      likely co-expressed by at least several other mucin-secreting organs.

PMID- 1985114
TI  - Role of free fatty acids and insulin in determining free fatty acid and lipid
      oxidation in man.
AB  - Plasma FFA oxidation (measured by infusion of 14C-palmitate) and net lipid
      oxidation (indirect calorimetry) are both inhibited by insulin. The present study
      was designed to examine whether these insulin-mediated effects on lipid
      metabolism resulted from a decline in circulating FFA levels or from a direct
      action of the hormone on FFA/lipid oxidation. Nine subjects participated in two
      euglycemic insulin clamps, performed with and without heparin. During each
      insulin clamp study insulin was infused at two rates, 4 and 20 mU/m2.min for 120
      min. The studies were performed with indirect calorimetry and 3-3H-glucose and
      14C-palmitate infusion. During the control study plasma FFA fell from 610 +/- 46
      to 232 +/- 42 to 154 +/- 27 mumol/liter, respectively. When heparin was infused
      basal plasma FFA concentration remained constant. During the control study,
      FFA/lipid oxidation rates decreased in parallel with the fall in the plasma FFA
      concentration. During the insulin/heparin study, plasma 14C-FFA oxidation
      remained unchanged while net lipid oxidation decreased. In conclusion, when the
      plasma FFA concentration is maintained unchanged by heparin infusion, insulin has
      no direct effect on FFA turnover and disposal. These results thus suggest that
      plasma FFA oxidation is primarily determined by the plasma FFA concentration,
      while net lipid oxidation is regulated by both the plasma FFA and the insulin
      level.

PMID- 1985115
TI  - Macrophage-derived foam cells freshly isolated from rabbit atherosclerotic
      lesions degrade modified lipoproteins, promote oxidation of low-density
      lipoproteins, and contain oxidation-specific lipid-protein adducts.
AB  - Pure macrophage-derived foam cells (MFC) were isolated from the aortas of rabbits
      made atherosclerotic by balloon deendothelialization followed by diet-induced
      hypercholesterolemia. The MFC were isolated under sterile conditions using an
      enzymatic digestion procedure and discontinuous density gradient centrifugation.
      The purity of the MFC preparations was verified immunocytochemically with the
      macrophage specific monoclonal antibody RAM-11. MFC plated in medium containing
      0.5% FCS for 24 h contained approximately 600 micrograms cholesterol per mg cell
      protein, 80% of which was esterified cholesterol. The MFC specifically degraded
      low density lipoprotein (LDL), acetyl-LDL, copper oxidized LDL, and beta-very low
      density lipoprotein (beta-VLDL) at rates comparable to mouse peritoneal
      macrophages (MPM) in 5-h assays. MFC within sections of the atherosclerotic
      lesions from the ballooned rabbits as well as the MFC isolated from the same
      lesions in the presence of antioxidants, exhibited positive immunoreactivity with
      polyclonal guinea pig antisera and mouse monoclonal antibodies directed against
      malondialdehyde-LDL, and 4-hydroxynonal-LDL. The MFC also exhibited the capacity
      to induce the oxidation of LDL at rates comparable to those exhibited by MPM and
      rabbit aortic endothelial cells. These data provide direct evidence that arterial
      wall macrophages express modified LDL receptors in vivo, contain epitopes found
      in oxidized-LDL and are capable of oxidizing LDL even when maximally loaded with
      cholesterol.

PMID- 1985116
TI  - Activated B lymphocytes from human immunodeficiency virus-infected individuals
      induce virus expression in infected T cells and a promonocytic cell line, U1.
AB  - Freshly isolated B lymphocytes from patients infected with human immunodeficiency
      virus (HIV), in contrast to B cells from normal controls, were shown to induce
      viral expression in two cell lines: ACH-2, a T cell line, and U1, a promonocytic
      cell line, which are chronically infected with HIV, as well as in autologous T
      cells. In 10 out of 10 HIV-infected individuals with hypergammaglobulinemia,
      spontaneous HIV-inductive capacity was found with highly purified peripheral
      blood B cells, whereas peripheral blood or tonsillar B cells from six healthy,
      HIV-negative donors did not induce HIV expression unless the cells were
      stimulated in vitro. The induction of HIV expression was observed in direct
      coculture experiments of B lymphocytes and HIV-infected cells, and could also be
      mediated by supernatants from cultures of B cells. Significantly higher amounts
      of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) were detected
      in the B cell culture supernatants from HIV-infected patients with
      hypergammaglobulinemia (IL-6: mean = 536 pg/ml; TNF-alpha: mean = 493 pg/ml), as
      compared with normal uninfected controls (IL-6: mean = 18 pg/ml; TNF-alpha: mean
      = 23 pg/ml). Antibodies against these cytokines abolished the HIV-inductive
      capacity of B cells. We conclude that in vivo activated B cells in HIV-infected
      individuals can upregulate the expression of virus in infected cells by secreting
      cytokines such as TNF-alpha and IL-6, and, therefore, may play a role in the
      progression of HIV infection.

PMID- 1985117
TI  - Minor histocompatibility antigen-specific cytotoxic T cell lines, capable of
      lysing human hematopoietic progenitor cells, can be generated in vitro by
      stimulation with HLA-identical bone marrow cells.
AB  - Recipient-antidonor alloreactivity before HLA genotypically identical bone marrow
      transplantation (BMT) between donor-recipient pairs that are negative in the
      mixed lymphocyte reaction (MLR), the cell-mediated lympholysis (CML) assay, and
      the lymphocyte crossmatch was not detectable in the majority of cases, using
      recipient peripheral blood lymphocytes (PBL) collected before BMT as responder
      cells and donor PBL as stimulator cells. However, when donor bone marrow
      mononuclear cells (BMMNC) instead of PBL were used as stimulator cells, we could
      detect donor-specific alloreactivity in 7 of 10 HLA genotypically identical donor
      recipient pairs. To demonstrate that this alloreactivity was minor
      histocompatibility (mH) antigen specific and not directed against HLA class I
      splits or variants, two cytotoxic T lymphocyte (CTL) lines were tested in further
      detail against phytohemagglutinin (PHA) blasts from pairs of HLA genotypically
      identical siblings positive for the HLA class I restriction molecule. Both CTL
      lines recognized mH antigens, as illustrated by the differential recognition of
      PHA blasts of one of the two siblings from several pairs. The potential role of
      these mH antigen-specific CTLs in bone marrow graft rejection was demonstrated by
      the mH antigen-specific growth inhibition of hematopoietic progenitor cells from
      the original bone marrow donor and from HLA class I restriction molecule-positive
      individuals who expressed the mH antigens on their PBL and BMMNC. Our assay can
      be used in HLA genotypically identical BMT to detect a recipient-antidonor
      response, directed against cellularly defined mH antigens expressed on donor HPC,
      BMMNC, and PBL, before transplantation.

PMID- 1985119
TI  - cDNA cloning of the B cell membrane protein CD22: a mediator of B-B cell
      interactions.
AB  - We have cloned a full-length cDNA for the B cell membrane protein CD22, which is
      referred to as B lymphocyte cell adhesion molecule (BL-CAM). Using subtractive
      hybridization techniques, several B lymphocyte-specific cDNAs were isolated.
      Northern blot analysis with one of the clones, clone 66, revealed expression in
      normal activated B cells and a variety of B cell lines, but not in normal
      activated T cells, T cell lines, Hela cells, or several tissues, including brain
      and placenta. One major transcript of approximately 3.3 kb was found in B cells
      although several smaller transcripts were also present in low amounts
      (approximately 2.6, 2.3, and 1.6 kb). Sequence analysis of a full-length cDNA
      clone revealed an open reading frame of 2,541 bases coding for a predicted
      protein of 847 amino acids with a molecular mass of 95 kD. The BL-CAM cDNA is
      nearly identical to a recently isolated cDNA clone for CD22, with the exception
      of an additional 531 bases in the coding region of BL-CAM. BL-CAM has a predicted
      transmembrane spanning region and a 140-amino acid intracytoplasmic domain.
      Search of the National Biological Research Foundation protein database revealed
      that this protein is a member of the immunoglobulin super family and that it had
      significant homology with three homotypic cell adhesion proteins:
      carcinoembryonic antigen (29% identity over 460 amino acids), myelin-associated
      glycoprotein (27% identity over 425 amino acids), and neural cell adhesion
      molecule (21.5% over 274 amino acids). Northern blot analysis revealed low-level
      BL-CAM mRNA expression in unactivated tonsillar B cells, which was rapidly
      increased after B cell activation with Staphylococcus aureus Cowan strain 1 and
      phorbol myristate acetate, but not by various cytokines, including interleukin 4
      (IL-4), IL-6, and gamma interferon. In situ hybridization with an antisense BL
      CAM RNA probe revealed expression in B cell-rich areas in tonsil and lymph node,
      although the most striking hybridization was in the germinal centers. COS cells
      transfected with a BL-CAM expression vector were immunofluorescently stained
      positively with two different CD22 antibodies, each of which recognizes a
      different epitope. Additionally, both normal tonsil B cells and a B cell line
      were found to adhere to COS transfected with BL-CAM in the sense but not the
      antisense direction.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1985118
TI  - Bromide-dependent toxicity of eosinophil peroxidase for endothelium and isolated
      working rat hearts: a model for eosinophilic endocarditis.
AB  - Eosinophilic endocarditis is a potentially lethal complication of chronic
      peripheral blood hypereosinophilia. We hypothesized that eosinophil peroxidase
      (EPO), an abundant eosinophil (EO) cationic granule protein, promotes
      eosinophilic endocarditis by binding to negatively charged endocardium, and there
      generating cytotoxic oxidants. Using an immunocytochemical technique, we
      demonstrated endocardial deposition of EPO in the heart of a patient with
      hypereosinophilic heart disease. Because EPO preferentially oxidizes Br- to
      hypobromous acid (HOBr) rather than Cl- to hypochlorous acid (HOCl) at
      physiologic halide concentrations, we characterized the Br(-)-dependent toxicity
      of both activated EOs and purified human EPO towards several types of endothelial
      cells and isolated working rat hearts. In RPMI supplemented with 100 microM Br-,
      phorbol myristate acetate-activated EOs, but not polymorphonuclear leukocytes,
      caused 1.8-3.6 times as much 51Cr release from four types of endothelial cell
      monolayers as in RPMI alone. H2O2 and purified human EPO, especially when bound
      to cell surfaces, mediated extraordinarily potent, completely Br(-)-dependent
      cytolysis of endothelial cells that was reversed by peroxidase inhibitors, HOBr
      scavengers, and competitive substrates. We further modeled eosinophilic
      endocarditis by instilling EPO into the left ventricles of isolated rat hearts,
      flushing unbound EPO, then perfusing them with a buffer containing 100 microM Br-
      and 1 microM H2O2. Acute congestive heart failure (evidenced by a precipitous
      decrement in rate pressure product, stroke volume work, aortic output, and MVO2
      to 0-33% of control values) ensued over 20 min, which deletion of EPO, Br-, or
      H2O2 completely abrogated. These findings raise the possibility that EPO bound to
      endocardial cells might utilize H2O2 generated either by overlying phagocytes or
      endogenous cardiac metabolism along with the virtually inexhaustible supply of Br
      from flowing blood to fuel HOBr-mediated cell damage. By this mechanism, EPO may
      play an important role in the pathogenesis of eosinophilic endocarditis.

PMID- 1985120
TI  - Successful engraftment of human postnatal thymus in severe combined immune
      deficient (SCID) mice: differential engraftment of thymic components with
      irradiation versus anti-asialo GM-1 immunosuppressive regimens.
AB  - To develop a model of human thymus growth in vivo, we have implanted postnatal
      human thymus under the renal capsule of severe combined immune deficient (SCID)
      mice and assayed for graft survival and graft characteristics 1-3 mo after
      engraftment. Three groups of SCID mice were engrafted with postnatal human
      thymus: untreated SCID mice, SCID mice pretreated with 400 cGy of gamma
      irradiation 1-5 d before engraftment, and SCID mice treated with intraperitoneal
      anti-asialo GM-1 antiserum every 4-5 d during engraftment. In the untreated group
      of SCID mice, only 37% of grafts survived and consisted of human thymic
      microenvironment components and human immature thymocytes. Irradiation of SCID
      mice before engraftment improved survival of human thymic grafts to 83%, but
      these grafts were largely devoid of thymocytes and contained only thymic
      microenvironment components with large numbers of thymic macrophages. Treatment
      of SCID mice with anti-asialo GM-1 antiserum throughout the engraftment period
      also promoted human thymus engraftment (70%) and induced SCID B cell Ig
      production (SCID[Ig+]) in 38% of animals. In SCID(Ig-) anti-asialo GM-1-treated
      mice, the human thymic grafts were similar in content to those in untreated SCID
      mice. However, in anti-asialo GM-1-treated animals with grafts that became
      SCID(Ig+), all animals were found to have mouse-human chimeric grafts in that the
      human thymic microenvironment (human fibroblasts, thymic epithelium, vessels) was
      colonized by murine T cells. These data demonstrate that human postnatal thymus
      will grow as xenografts in SCID mice, and that the components of human thymus
      that engraft are dependent on the immunosuppressive regimen used in recipient
      mice. A striking finding in this study was the induction of T and B lymphopoiesis
      in SCID mice by abrogation of NK cell activity with in vivo anti-asialo GM-1
      treatment. These data strongly suggest that asialo GM-1+ NK cells and/or
      macrophages play a role in mediation of suppression of lymphopoiesis in SCID
      mice.

PMID- 1985121
TI  - Allelic polymorphism in transcriptional regulatory regions of HLA-DQB genes.
AB  - Class II genes of the human major histocompatibility complex (MHC) are highly
      polymorphic. Allelic variation of structural genes provides diversity in immune
      cell interactions, contributing to the formation of the T cell repertoire and to
      susceptibility to certain autoimmune diseases. We now report that allelic
      polymorphism also exists in the promoter and upstream regulatory regions (URR) of
      human histocompatibility leukocyte antigen (HLA) class II genes. Nucleotide
      sequencing of these regulatory regions of seven alleles of the DQB locus reveals
      a number of allele-specific polymorphisms, some of which lie in functionally
      critical consensus regions thought to be highly conserved in class II promoters.
      These sequence differences also correspond to allelic differences in binding of
      nuclear proteins to the URR. Fragments of the URR of two DQB alleles were
      analyzed for binding to nuclear proteins extracted from human B lymphoblastoid
      cell lines (B-LCL). Gel retardation assays showed substantially different banding
      patterns to the two promoters, including prominent variation in nuclear protein
      binding to the partially conserved X box regions and a novel upstream polymorphic
      sequence element. Comparison of these two polymorphic alleles in a transient
      expression system demonstrated a marked difference in their promoter strengths
      determined by relative abilities to initiate transcription of the chloramphenicol
      acetyltransferase reporter gene in human B-LCL. Shuttling of URR sequences
      between alleles showed that functional variation corresponded to both the X box
      and upstream sequence polymorphic sites. These findings identify an important
      source of MHC class II diversity, and suggest the possibility that such
      regulatory region polymorphisms may confer allelic differences in expression,
      inducibility, and/or tissue specificity of class II molecules.

PMID- 1985122
TI  - Adoptive transfer of neonatal T lymphocytes rescues immunoglobulin production in
      mice with severe combined immune deficiency.
AB  - Mice with the autosomal recessive severe combined immune deficiency (scid)
      mutation lack mature lymphocytes because of defective joining of T cell receptor
      and immunoglobulin (Ig) gene segments. Penetrance of this mutation is incomplete
      since 10-25% of SCID mice produce some T or B lymphocytes. This "leaky" phenotype
      could be due to a reversion of the mutation in some mice or to a constant, low
      frequency of functional lymphocytes generated in all SCID mice with variable
      survival of such cells. We report here that all SCID mice can be stimulated to
      produce functional B cells by the transfer of normal neonatal, but not adult, T
      cells. T cell-induced rescue of C.B-17scid B cells results in high levels of Ig
      expressing the Ighb allotype of the SCID recipient. These results show that all
      SCID mice generate some functional B cells, the majority of which do not survive
      in the absence of a subset of T cells present in high frequency in the neonate.

PMID- 1985123
TI  - Congenital osteoclast deficiency in osteopetrotic (op/op) mice is cured by
      injections of macrophage colony-stimulating factor.
AB  - Osteopetrotic (op/op) mice have a severe deficiency of osteoclasts, monocytes,
      and peritoneal macrophages because of a defect in the production of functional
      macrophage colony-stimulating factor (M-CSF) resulting from a mutation within the
      M-CSF gene. In this study, we examined whether daily 5-microgram injections of
      purified recombinant human M-CSF (rhM-CSF) for 14 d would cure these deficiencies
      in the mutant mice. Monocytes in the peripheral blood of the op/op mice were
      significantly increased in number after subcutaneous injections of the factor two
      or three times a day. In contrast, osteopetrosis in the long bones of op/op mice
      was completely cured by only one injection of rhM-CSF per day. Bone trabeculae in
      the diaphyses were removed. Many osteoclasts were detected on the surface of bone
      trabeculae in the metaphyses. Although development of tooth germs of uninjected
      op/op mice was impaired, rhM-CSF injection restored the development of molar
      tooth germs and led to tooth eruption as a consequence of the recovery of bone
      resorbing activity. These results demonstrate that M-CSF is one of the factors
      responsible for the differentiation of osteoclasts and monocyte/macrophages under
      physiological conditions.

PMID- 1985124
TI  - A selective defect of interferon alpha production in human immunodeficiency virus
      infected monocytes.

PMID- 1985125
TI  - Effect of antigen/antibody ratio on macrophage uptake, processing, and
      presentation to T cells of antigen complexed with polyclonal antibodies.
AB  - Activation of a galactosidase-specific murine T hybridoma clone and of a human
      tetanus toxoid-specific T clone by antigen-presenting cells (APC) was used to
      evaluate the regulatory function of antibodies complexed with the relevant
      antigen. Complexed antigen, in fact, is taken up with high efficiency thanks to
      Fc receptors borne by APC. Antibody/antigen ratio in the complexes proved to be a
      critical parameter in enhancing antigen presentation. Complexes in moderate
      antibody excess provided optimal T cell activation independently of the physical
      state of the complexes (precipitated by a second antibody or solubilized by
      complement). Complexes in extreme antibody excess, on the contrary, did not yield
      T cell activation although taken up by APC efficiently. The effect of antibodies
      at extreme excess was observed with substimulatory dose of antigen (loss of
      potentiation) and with optimal dose of antigen (loss of stimulation). An excess
      of specific polyclonal antibodies hampers proteolytic degradation of antigen in
      vitro, supporting the view that a similar mechanism may operate within the APC
      that have internalized immune complexes in extreme antibody excess. The
      possibility that immune complex forming in extreme antibody excess may turn off
      the T cell response is proposed as a regulatory mechanism.

PMID- 1985126
TI  - A mouse model of Leishmania braziliensis braziliensis infection produced by
      coinjection with sand fly saliva.
AB  - To development a reliable murine model of Leishmania braziliensis braziliensis
      infection, parasites were injected into BALB/c mice in the presence of
      phlebotomine sand fly salivary gland lysates, which have previously been shown to
      greatly increase the infectivity of L. major in mice. When injected with salivary
      gland lysates, L. braziliensis braziliensis produced progressively enlarging
      cutaneous nodules, containing many macrophages filled with Leishmania
      amastigotes. In contrast, L. braziliensis injected without gland extracts
      produced small and rapidly regressing lesions. Isoenzyme analysis, monoclonal
      antibodies, and the polymerase chain reaction with L. braziliensis-specific
      oligonucleotide primers and probes confirmed that parasites causing the lesions
      were L. braziliensis.

PMID- 1985127
TI  - Peripheral tolerance to alloantigen results from altered regulation of the
      interleukin 2 pathway.
AB  - Tolerance to alloantigen may be induced in rats by administration of blood
      followed by transplantation of a renal allograft. The mechanism of this tolerance
      was investigated by directly analyzing the functional activity of graft
      infiltrating cells. We have previously shown cytotoxic T lymphocyte infiltration
      of, and major histocompatibility complex induction on, grafts of tolerant
      animals. We now report that cells isolated from the grafts of tolerant rats show
      a reduced expression of the p55 interleukin 2 receptor (IL-2R) chain on the cell
      surface compared with that seen on the cells of untreated animals. Scatchard
      analysis further reveals low expression of high affinity IL-2R. This is due to
      reduced transcription of both IL-2R alpha and beta chain mRNAs and results in a
      reduced ability of cells to proliferate in response to IL-2. Cells isolated from
      tolerant animals are unable to make biologically active IL-2 in culture, whereas
      cells from untreated animals make high levels. This is not reflected at the mRNA
      level as the IL-2 gene is induced in both tolerant and untreated animals to
      similar levels. The induction of tolerance is abrogated by administration of
      recombinant IL-2 to animals at the time of transplantation. Thus, we conclude
      that an altered regulation of the IL-2 pathway results in tolerance in these
      alloantigen-treated and transplanted animals.

PMID- 1985128
TI  - Art of therapeutic communication.

PMID- 1985129
TI  - Methodological classification.

PMID- 1985131
TI  - The primary care research program of AHCPR.

PMID- 1985130
TI  - The problem of teenage pregnancy.

PMID- 1985132
TI  - Evolution of a specialty journal.

PMID- 1985133
TI  - AAFP and JFP: a new collaboration.

PMID- 1985134
TI  - The effects of family functioning on infant birthweight.
AB  - A prospective cohort study was undertaken to evaluate the relationship of family
      functioning to infant birthweight adjusted for length of gestation. The mother's
      perception of family functioning was assessed at the initial prenatal visit using
      the Family Adaptability and Cohesion Evaluation Scales (FACES II). All obstetric
      patients at four family medicine clinics from April 1984 through April 1987 whose
      initial prenatal visits occurred by the 28th week of gestation were invited to
      participate; 95% chose to do so. Information was obtained on 833 mother-infant
      pairs. Listwise deletion on any one variable reduced the sample to 772 with no
      apparent bias in the dependent or predetermined variables. Twelve percent of the
      families were considered to be dysfunctional by scoring on the extremes of both
      the cohesion and adaptability continua of the self-report FACES II questionnaire.
      Infant birthweight was regressed on length of gestation and other known
      biomedical, anthropometric, risk-behavior, and sociodemographic determinants, as
      well as family functioning. Women who perceived their families as dysfunctional
      were delivered of infants who weighed on the average 126.4 g (95% CI 37.4, 215.4)
      less than infants born to women from functional families (P = .0055), after
      adjusting for other known determinants. Family functioning also was found to
      modify the effects of prepregnancy weight and infant sex on infant birthweight.

PMID- 1985135
TI  - Physician practice for cardiovascular disease risk-factor reduction in six upper
      Midwestern communities.
AB  - Preventive practice for coronary heart disease risk is increasingly accepted in
      the medical community. To determine the extent and characteristics of treatment
      advice for high blood pressure, blood cholesterol, and cigarette smoking, 274
      randomly selected primary care physicians were interviewed by telephone in six
      Midwestern cities. Participation in the survey was 90%. Reported care for high
      blood pressure was consistent with national guidelines. Management of high blood
      cholesterol varied significantly among physicians and frequently differed from
      national recommendations. Although consensus existed on the importance of
      advising cigarette smoking cessation, reported approaches differed. The results
      observed indicate improved preventive practice compared with earlier surveys and
      recent national reports. Continued improvement, however, is needed in cholesterol
      and smoking-cessation management.

PMID- 1985136
TI  - Multiple family member visits to family physicians. Terminology, classification,
      and implications.
AB  - A study was designed to investigate "the family as the unit of care" in family
      medicine consultations from the patient's end of the physician-patient axis,
      unlike most previous related studies, which have concentrated on it from the
      physician's perspective. During 2 separate weeks in November 1987 and February
      1988, nine Israeli family physicians collected demographic and family-related
      data concerning the spontaneous visiting patterns generated by 1156 persons (899
      patients and 257 nonpatients) who attended 796 separate consultations at their
      clinics during this time. More than one patient attended 12% of the
      consultations, and more than one person, patient or nonpatient, was present at
      36%. At 31% of the consultations children alone or children and adults were
      recorded as patients (child consultations), and at 69% only adult patients were
      present (adult consultations). Adults were recorded as second or third patients
      at 19% of the child consultations but at only 5% of the adult consultations. The
      child consultations alone yielded 86% of all the nonpatients documented. Basic
      terminology and methodology for investigating such multiple family member visits
      to family physicians is discussed as well as the composition of the different
      family units encountered and their possible significance.

PMID- 1985137
TI  - Payment mechanism and patterns of use of medical services: the example of
      hypertension.
AB  - This study explores the relationship between the use of medical services by
      hypertensive patients and mechanisms for payment within a single primary care
      practice. Three payment mechanisms were explored: public assistance, a capitated
      health maintenance organization (HMO), and fee-for-service. Patterns were
      examined across reimbursement type for the following variables: age, sex, visit
      reason, number of visits, medications, tests ordered, referrals made, and
      recommendations for follow-up visits. Illness severity was controlled in two
      ways: (1) by the study being focused on one diagnosis--mild to moderate
      hypertension, and (2) by concurrent chronic illnesses being enumerated and
      included in the analysis. Medical visits to the physician were examined over a 2
      year period for 25 to 30 patients randomly sampled from each of the three payment
      mechanisms. Statistically significant differences were found for patient
      behaviors (total number of patient visits) and physician behaviors (number of
      medications and recommendations for revisits). The highest visit frequency was
      found for those on public assistance, followed closely by those covered by an
      HMO, and more distantly by those choosing fee-for-service. In a climate of cost
      consciousness, further study is needed to explore the impact of reimbursement
      mechanisms on the use of health care services.

PMID- 1985138
TI  - AIDS: family physicians' attitudes and experiences.
AB  - A study was developed to examine the current experiences and opinions of a
      national sample of family physicians with regard to acquired immunodeficiency
      syndrome (AIDS). The survey response rate was 72.5% (757 questionnaires were
      returned out of a sample of 1044). Approximately 47% of respondents have cared
      for an HIV-infected patients. This percentage varied from a low of 31.4% in the
      Midwest to as high as 56.1% on the East Coast. Thirty-two percent of family
      physicians practicing in communities of fewer than 2500 have dealt with this
      illness, while 60% of those in communities of greater than 100,000 have done so.
      Seventy-seven percent of respondents are willing to provide care to HIV-infected
      individuals; 62.9% believe that physicians have a right to refuse to care for a
      patient because he or she is infected with the AIDS virus. Forty percent believe
      that they would lose patients if it were known that they were caring for an AIDS
      patient in their office. Finally, the vast majority of those surveyed favor
      required partner notification and would inform the sexual partner of an HIV
      positive patient if the patient refused to do so.

PMID- 1985139
TI  - Impact of a family physician-staffed maternity center on obstetric services in a
      rural region.
AB  - In the past few years rural hospitals have found obstetric care increasingly
      difficult to provide. A trend toward family physicians abandoning the practice of
      obstetrics has been a major obstacle for these hospitals. Malpractice cost and
      pressures, professional isolation, and inadequate training have all been cited as
      reasons that family physicians in rural areas have stopped delivering babies.
      Faced with a large number of women giving birth without prenatal care, a hospital
      in eastern Kentucky began a regional primary care obstetric unit to assure that
      obstetric care would be available to all patients who needed it. The hospital
      chose to staff the maternity center with family physicians so it could offer a
      family-centered obstetric program and newborn care. Since the opening of the
      maternity center in 1985, hospital deliveries have increased over 30%, while the
      percentage of patients who give birth without prenatal care has fallen from 3.0%
      to 0.7%. This report describes the factors behind the creation of the maternity
      center, its effect on the hospital, and its effect on the family physicians who
      serve on its staff.

PMID- 1985141
TI  - Smoking patterns in a low-income urban population. A challenge to smoking
      cessation efforts.

PMID- 1985140
TI  - Computer-generated physician and patient reminders. Tools to improve population
      adherence to selected preventive services.
AB  - Despite an emerging consensus on appropriate preventive services, a minority of
      patients receive them. A study was undertaken to assess the impact of computer
      generated reminders to adult patients, their physicians, or both patients and
      physicians on adherence to five recommended preventive services: cholesterol
      measurements, fecal occult blood testing, mammography, Papanicolaou smears, and
      tetanus immunization. During the academic year 1988-1989, all 7397 adult patients
      and their 49 physicians in a university family medicine clinical practice were
      randomized by practice group into one of four study groups: control, physician
      reminders, patient reminders, and both physician and patient reminders. Adherence
      was defined in community-oriented terms: the percentage of patients within each
      group who had received the preventive service in the recommended interval. During
      the study period, adherence to four of the five preventive services increased
      significantly, with the largest increases in the physician and patient reminder
      group: cholesterol measurements increased from 19.5% to 38.1%, fecal occult blood
      testing 9.3% to 27.0%, mammography 11.4% to 27.1%, and tetanus immunization 23.4%
      to 35.4% (for each increase, P less than .0001, McNemar's chi-square test). In
      general, increases were greater in blacks and in patients with any form of
      insurance coverage. Computer-based physician and patient reminder systems have
      great promise of improving adherence to preventive services in primary care
      settings.

PMID- 1985142
TI  - Timolol eyedrop-induced fatal bronchospasm in an asthmatic patient.

PMID- 1985143
TI  - Florid refractory schizophrenias that turn out to be treatable variants of HLA
      associated narcolepsy.
AB  - Narcolepsy in which the hallucinatory component is unusually prominent may lead
      to the development of an illness indistinguishable from the schizophrenic
      syndrome. Psychotic symptoms dominate the symptomatology, so that the primary
      illness is obscured. Five patients are described for whom conventional
      antipsychotic drugs were ineffectual, but for whom treatment with stimulants
      produced substantial improvement. The diagnosis of narcolepsy was confirmed by
      Human Leukocyte Antigen typing and sleep laboratory testing. These results
      support the "REM intrusion" hypothesis of the causation of schizophrenia in as
      many as 7% of a series of schizophrenic patients. Implications for diagnosis and
      treatment are discussed.

PMID- 1985144
TI  - The place of culture in psychiatric nosology: Taijin kyofusho and DSM-III-R.
AB  - The place of culture in psychiatric nosology is explored through the example of
      taijin kyofusho (TKS), a common Japanese psychiatric disorder characterized by a
      fear of offending or hurting others through one's awkward social behavior or an
      imagined physical defect. Although variants of this disorder have been described
      in other cultures (e.g., dysmorphobia), the full spectrum appears to be confined
      to Japan. TKS can be understood as a pathological amplification of culture
      specific concerns about the social presentation of self and the impact of
      improper conduct on the well-being of others. Both social interaction and
      constitutional vulnerability may contribute to the cognitive processes that
      underlie TKS. The salience of cultural differences for psychiatric nosology then
      depends on whether the clinical focus is on disordered biology, individual
      psychology and experience, or the social context of behavior. Any attempt to
      include cultural variation in psychiatric diagnoses must begin by making explicit
      the intended use of the classification because different social contexts and
      clinical goals demand alternative diagnostic schemes.

PMID- 1985145
TI  - Predicting vulnerability to hopelessness. A longitudinal analysis.
AB  - The role of loneliness, irrational beliefs, and deficient reasons for living in
      predicting vulnerability to hopelessness under conditions of negative life stress
      was examined. Subjects (N = 178) completed the UCLA Loneliness Scale. Rational
      Beliefs Inventory, and the Reasons for Living Inventory at the beginning of the
      semester. Then, at midterm, measures of negative life stress, depression, and
      hopelessness were obtained from the same subjects. It was hypothesized that the
      vulnerability factors would interact with negative life stress to predict
      hopelessness, independent of depressed mood. The results of multiple regression
      analyses supported this hypothesis. Implications for research, prevention, and
      treatment are noted.

PMID- 1985146
TI  - Combat-related PTSD and psychosocial adjustment problems among substance abusing
      veterans.
AB  - The purpose of this study were the following: a) to determine the prevalence of
      combat-related posttraumatic stress disorder (PTSD) symptoms among veterans
      seeking assistance at a Veterans Administration medical center substance abuse
      treatment facility, b) to examine the relative contribution of Vietnam war zone
      variables to PTSD symptom development, and c) to study psychosocial adjustment
      problems associated with Vietnam combat exposure and with PTSD symptoms among
      help-seeking substance abusing men. Of 489 male veterans presenting for
      treatment, 10.7% had significant Vietnam combat-related PTSD symptoms as measured
      by the Mississippi Scale for Combat-Related PTSD. Clinically significant PTSD
      symptoms occurred among 46% of the subsample of combat-exposed Vietnam veterans
      with substance abuse problems. Degree of combat exposure was the most important
      military stressor that distinguished Vietnam veterans with PTSD from those
      without PTSD, but the groups also differed on age of war zone duty, duration of
      war zone duty, and whether they were wounded. Veterans who served in Vietnam did
      not differ from veterans who had no war zone duty on various parameters of
      psychosocial adjustment. However, the subgroup of Vietnam veterans with PTSD
      symptoms reported significantly greater psychosocial adjustment problems than
      their counterparts who did not have PTSD. The deleterious effects associated with
      combat-related PTSD appeared to be confined to adjunctive psychiatric
      difficulties and unemployment and did not increase risk of arrests for antisocial
      conduct beyond that found for veterans without PTSD. Methodological and clinical
      implications of these findings are discussed.

PMID- 1985148
TI  - Assessment and treatment of torture victims: a critical review.
AB  - This paper presents the main issues in the diagnosis and treatment of psychiatric
      sequelae in torture victims. The concept of post traumatic stress disorder is
      used to organize literature on psychiatric casualties resulting from massive
      psychic trauma, e.g., the Nazi Holocaust, the Vietnam and Israeli wars, and the
      current world epidemic of torture. Torture is a unique human made stressor
      resulting in category-specific diagnostic symptoms. Medical assessment can be
      complemented with photographs, x-rays, electroencephalograms, and sleep studies.
      Individual psychotherapy and group techniques focus on the issues of denial and
      trust, loss, survivor guilt, and reparation. Programs of psychological and social
      rehabilitation and treatment with benzodiazepines, tricyclic antidepressants, and
      other compounds are reviewed. Future research needs include the conceptualization
      of the trauma of torture and its sequelae in broader terms, the application of
      standardized measurements to facilitate international comparisons, and the
      testing of various approaches to intervention in an experimental design. An
      ethical physician must resist the pressures of totalitarian governments to assume
      neutrality in the presence of human rights violations affecting his/her patients.

PMID- 1985147
TI  - Psychological absorption. Affect investment in marijuana intoxication.
AB  - Absorption (a trait capacity for total attentional involvement) was reported to
      increase during episodes of marijuana intoxication. Several subsets of the
      absorption scale items specifically characterized marijuana intoxication, and
      groups of users and nonusers showed differential affective involvement with these
      experiences. Additionally, within the drug-using group, a positive correlation
      between frequency of marijuana use and affective ratings of these experiences was
      found. The findings support the hypothesis that a specific type of alteration in
      consciousness that enhances capacity for total attentional involvement
      (absorption) characterizes marijuana intoxication, and that this enhancement may
      act as a reinforcer, possibly influencing future use.

PMID- 1985149
TI  - Association between post-dexamethasone cortisol level and blood pressure in
      depressed inpatients.
AB  - We examined the clinical data for 230 depressed inpatients who had completed a
      dexamethasone suppression test (DST) to determine whether those with an elevated
      post-DST serum cortisol level exhibited any of the classic physiological stigmata
      of Cushing's syndrome. Hypertension was significantly more frequent among DST
      nonsuppressors (21.2%) than among normal suppressors (11.3%). Percent blood
      lymphocyte count was significantly lower among nonsuppressors. Confounders such
      as gender, age, body weight, and use of antihypertensives did not account for the
      findings. Implications for morbidity and mortality rates among patients with
      affective disorder are discussed.

PMID- 1985150
TI  - Neuropsychiatric symptoms associated with idiopathic calcification of the basal
      ganglia.

PMID- 1985151
TI  - A self-destructive variant of jactatio capitis nocturna.

PMID- 1985152
TI  - Delayed central nervous system myelination in the sudden infant death syndrome.
AB  - This study was designed to assess whether development of the central nervous
      system (CNS) is delayed in victims of the sudden infant death syndrome (SIDS). We
      selected the parameter of myelination because it is a continuously changing and
      readily accessible marker of CNS development in the SIDS age-range. We assessed
      myelination blindly in 61 SIDS and 89 autopsy controls. In 62 sites the degree of
      myelination was visually graded in myelin-stained histological sections on an
      ordinal scale of 0-4 using the inferior cerebellar peduncle as an internal
      standard of degree 3. Cases were stratified by postconceptional age at death and
      SIDS and controls were compared with respect to myelin degree at each site.
      Significantly delayed myelination (p less than 0.05) occurred in the SIDS group
      in 25 of the 62 sites examined. Hypomyelination affected fiber systems in which
      myelination is initiated before or after birth and which myelinate with different
      tempos and preferentially affect pyramidal and cerebellar (somatomotor) and
      prefrontal-temporal-limbic (visceromotor) systems. Hypomyelination was not
      associated with individual clinicopathologic variables in the SIDS group. Somatic
      growth and brain weight were significantly greater in SIDS than controls.
      Therefore, we suggest that SIDS is associated with a developmental CNS disorder.
      Although delayed CNS myelination most likely shares a common antecedent with
      sudden death and is not its cause, the role of somato- and viscero-motor systems
      in central cardiorespiratory control and arousal warrants further analysis in
      SIDS.

PMID- 1985153
TI  - The neuromuscular pathology of the Eosinophilia-Myalgia syndrome.
AB  - The Eosinophilia-Myalgia Syndrome (EMS) is a recently reorganized disorder in
      patients ingesting pharmacologic doses of L-tryptophan. We studied the lesions of
      skeletal muscle, peripheral nerve and skin in 12 cases of EMS. Perimyositis was
      severe in four, moderate in two, mild in three and absent in three cases. The
      lesions contained many eosinophils, T-helper cells, mast cells and activated
      macrophages. Type 2 myofiber atrophy was present in five cases and in one, this
      was the only pathologic finding. Severe epineurial inflammation was seen in the
      three sural nerve biopsies. Indirect evidence for peripheral neurologic
      involvement in three other cases consisted of inflammation surrounding
      intramuscular nerve twigs (two cases) and neurogenic atrophy (one case).
      Phlebitis accompanied the connective tissue inflammation in five cases and
      endarteritis in one. Fasciitis was present in three of four skin biopsies and
      dermal fibrosis in one.

PMID- 1985154
TI  - Effect of methotrexate on cell cycle and DNA synthesis of astrocytes in primary
      culture: flow cytometric studies.
AB  - Relatively pure population of astrocytes in primary culture were examined by flow
      cytometry at various time intervals after exposure to 1, 10 and 100 microM of
      methotrexate (MTX). The percentage population of cells in different phases of the
      cell cycle was determined using propidium iodide (PI) to measure cellular DNA
      content. DNA synthesis was assessed by measuring the fluorescence intensity of
      FITC-conjugated antibody to bromodeoxyuridine (BrdUrd). The two parameters were
      correlated to determine the location of BrdUrd-incorporating cells within the
      cell cycle. Exposure of astrocytes to MTX caused a consistent increase in number
      of cells in S-phase which correlated with the increase in BrdUrd incorporation.
      These studies provide supportive evidence that the astrogliosis seen in MTX
      encephalopathy may be due to a primary involvement of astrocytes.

PMID- 1985155
TI  - Free and peptide-bound amino acids as indicators of ischemic damage of the rabbit
      spinal cord.
AB  - The concentrations of free and peptide-bound amino acids aspartate (Asp),
      glutamate (Glu), glycine (Gly) and gamma-aminobutyric acid (GABA) were studied
      following ischemia and recirculation in the ventral and dorsal gray matter of the
      rabbit spinal cord. No changes in the concentration of amino acids following ten
      minutes (min) of ischemia and four days of recovery were found. The most
      significant change after 20 min, and especially 40 min, of ischemia was a
      decrease in free Asp and GABA levels in both parts of the gray matter. The
      relatively greater decrease in the concentration of free amino acids in the
      ventral horns corresponds with the greater morphological damage to this part of
      spinal cord following ischemia. Following 40 min of ischemia and recirculation
      decrease in peptide-bound Glu in the ventral horns and Asp and Glu in the dorsal
      horns was found.

PMID- 1985156
TI  - Hippocampal lesions in dominantly inherited Alzheimer's disease.
AB  - We compared hippocampal lesions in three pedigrees of Familial Alzheimer's
      Disease (FAD). In these pedigrees, the disease is inherited as an autosomal
      dominant disorder and has been linked to DNA markers on chromosome 21. In eight
      cases of FAD (four from one pedigree and two each from two others) we quantified
      neurofibrillary tangles (NFT) and senile plaques (SP) in hippocampal subdivision
      CA1-4, subiculum, presubiculum, and dentate gyrus. We observed consistent
      patterns of the distribution of lesions: The highest density of NFT and SP was
      present in CA1-2; virtually no SP or NFT were present in presubiculum; SP
      diameter was consistently greatest in CA4. We found no overall differences among
      pedigrees in total densities of NFT and SP, but statistical analyses disclosed
      that an uncommon type of SP was disproportionately present in two pedigrees. This
      type of SP was usually restricted to CA4, had a marked amyloid core devoid of
      argyrophilic neurites. These studies also disclosed inter- and intrafamilial
      heterogeneity of lesion distribution (including congophilic angiopathy and
      cerebellar plaques) in these three pedigrees.

PMID- 1985157
TI  - What would you do if this were your ... wife, sister, mother, self?

PMID- 1985158
TI  - Continuous infusion carboplatin on a 21-day schedule: a phase I and
      pharmacokinetic study.
AB  - A phase I study with continuous infusion carboplatin for 21 days every 6 weeks
      using a venous access port and portable pump was performed over a dose range of
      12 to 32 mg/m2/d, with increments of 2 mg/m2/d. Forty-four patients received 107
      courses (median, two; range, one to nine). World Health Organization (WHO) grade
      III/IV leukopenia and thrombocytopenia occurred in one of seven patients at 30
      mg/m2/d, and in two of six and four of six patients at 32 mg/m2/d. Cumulative
      platelet depression was found at dose levels of 28 mg/m2/d or more. Median
      glomerular filtration rate (GFR) and effective renal plasma flow, monitored by
      radioisotope clearances at doses greater than or equal to 20 mg/m2/d, decreased
      8.2% (P less than .05) and 10.9% (P less than .01) after two courses. There was a
      relationship (r = .50, P less than .0002) between the percentage of platelet
      depression and GFR. No other toxicity was observed. Of the 17 patients who were
      evaluable, one complete response and four partial responses were observed. In
      addition, six patients had stable disease. Pharmacokinetic analysis of total and
      ultrafiltrable platinum (UFPt) was performed by atomic absorption
      spectrophotometry. Steady-state plasma levels for UFPt were reached after 8
      hours. These levels could be detected from the 20 mg/m2/d dose. During steady
      state, carboplatin dose and UFPt plasma levels were not correlated, but steady
      state UFPt and GFR (r = -.27, P less than .05) were. Twenty-four percent of total
      platinum (Pt) was present as UFPt during steady state (x = 160 +/- 10
      micrograms/L). Total body clearance of UFPt exceeded GFR 2.2 times. Mean area
      under the curve (AUC) for UFPt during continuous infusion was 4,921.8 +/- 301.72
      mg.min/L. For total Pt, steady-state plasma levels were not reached; total Pt
      plasma levels increased between day 7 and day 21 (P less than .0001). There was a
      significant relation between total Pt serum levels day 7, 14, and 21 and the drug
      dose administered. Immunohistochemical analysis of DNA-bound Pt in leukocytes
      showed a linear increase from day 7 to day 14 to day 21 (r = .97) between DNA
      bound Pt and duration of infusion in individual patients. The maximum-tolerable
      dose of carboplatin is 30 mg/m2/d for 21 days (total dose 630 mg/m2) and is
      recommended for phase II studies.

PMID- 1985159
TI  - Cardiopulmonary resuscitation and the patient with cancer.
AB  - The records of 114 cancer patients suffering cardiopulmonary arrests (CPA) during
      a 3-year period at Memorial Sloan-Kettering Cancer Center (MSKCC) were
      retrospectively reviewed to identify variables predicting final outcome in these
      patients. Although 65.7% of the patients were successfully resuscitated, only 12
      (10.5%) were discharged alive from the hospital. Median survival after discharge
      was 150 days. By univariate and multivariate analysis, the only variable
      predicting the likelihood of a patient's being discharged alive after a CPA was
      the performance status of the patient at the time of admission to the hospital.
      Thus, a patient spending more than 50% of the time in bed at the time of
      admission had only a 2.3% chance of being discharged alive after CPA. A thorough
      discussion of these findings between physicians and patients and their families
      is strongly recommended at the time of admission to spare cancer patients
      unnecessary invasive resuscitative procedures.

PMID- 1985160
TI  - When to randomize?
AB  - Many clinical trials address the question of the duration of therapy or whether
      initial therapy can be improved by the addition of a consolidation or maintenance
      regimen. For such clinical trials, the question of when to perform the
      randomization is often difficult. Conventional statistical wisdom prescribes that
      randomization should take place as late as possible before treatment is effected.
      This is not always possible or desirable, however. In this report, we describe
      the factors that are influenced by the timing of randomization, quantify how
      timing affects these factors, and attempt to provide a tool to help investigators
      and statisticians determine the appropriate time to randomize for individual
      studies and particular circumstances.

PMID- 1985161
TI  - High survival rate in advanced-stage B-cell lymphomas and leukemias without CNS
      involvement with a short intensive polychemotherapy: results from the French
      Pediatric Oncology Society of a randomized trial of 216 children.
AB  - From April 1984 to December 1987, the French Pediatric Oncology Society (SFOP)
      organized a randomized trial for advanced-stage B-cell lymphoma without CNS
      involvement to study the possibility of reducing the length of treatment to 4
      months. After receiving the same three intensive six-drug induction courses based
      on high-dose fractionated cyclophosphamide, high-dose methotrexate (HD MTX), and
      cytarabine in continuous infusion, patients were evaluated for remission. Those
      who achieved complete remission (CR) were randomized between a long arm (five
      additional courses with two additional drugs; 16 weeks of treatment) and a short
      arm (two additional courses; 5 weeks). For patients in partial remission (PR),
      intensification of treatment was indicated. Two hundred sixteen patients were
      registered: 15 stage II nasopharyngeal and extensive facial tumors, 167 stage
      III, and 34 stage IV, 20 of the latter having more than 25% blast cells in bone
      marrow. The primary sites of involvement were abdomen in 172, head and neck in
      30, thorax in two, and other sites in 12. One hundred sixty-seven patients are
      alive in first CR with a minimum follow-up of 18 months; four are lost to follow
      up. Eight patients died from initial treatment failure, 14 died from toxicity or
      deaths unrelated to tumor or treatment, and 27 relapsed. The event-free survival
      (EFS), with a median follow-up of 38 months, is 78% (SE 3) for all the patients,
      73% (SE 11) for the stage II patients, 80% (SE 3) for the stage III patients, and
      68% (SE 8) for the stage IV and acute lymphoblastic leukemia (ALL) patients. One
      hundred sixty-six patients were randomized: 82 in the short arm and 84 in the
      long arm. EFS is, respectively, 89% and 87%. Statistical analysis confirms
      equivalence of both treatment arms with regard to EFS. Moreover, morbidity was
      lower in the short arm. This study confirms the high survival rate obtained in
      the previous LMB 0281 study without radiotherapy or debulking surgery and
      demonstrates the effectiveness of short treatment.

PMID- 1985162
TI  - HiC-COM: a 2-month intensive chemotherapy regimen for children with stage III and
      IV Burkitt's lymphoma and B-cell acute lymphoblastic leukemia.
AB  - We designed a protocol that included 2 months of intensive Cytoxan
      (cyclophosphamide; Bristol-Myers Co, Evansville, IN), high-dose methotrexate
      (MTX), high-dose cytarabine (ara-C), and vincristine (HiC-COM) to improve event
      free survival (EFS) for patients with advanced-stage Burkitt's lymphoma and B
      cell acute lymphoblastic leukemia (ALL). We also wished to test the feasibility
      of rapidly cycling Cytoxan and high-dose ara-C based on signs of early marrow
      recovery. Twenty patients including 12 with stage III Burkitt's lymphoma and
      eight with stage IV Burkitt's lymphoma or B-cell ALL were entered onto this pilot
      study. The rate of complete remission was 95%. Four patients have relapsed. The 2
      year actuarial EFS was 75% (median follow-up, 37 months). Two of the initial five
      patients developed transverse myelitis, which we believe may have been secondary
      to the concomitant administration of intrathecal (IT) and high-dose systemic ara
      C. We conclude that this short but intensive regimen is highly effective for
      patients with advanced Burkitt's lymphoma and B-cell ALL. EFS has improved over
      previous less intensive regimens, and is comparable to regimens of longer
      duration.

PMID- 1985163
TI  - A phase II study of combined methotrexate and teniposide infusions prior to
      reinduction therapy in relapsed childhood acute lymphoblastic leukemia: a
      Pediatric Oncology Group study.
AB  - Teniposide (VM-26) can increase intracellular methotrexate (MTX) and its
      polyglutamate derivatives in vitro and thus has the potential to improve the
      therapeutic index of regimens containing MTX. In this phase II study, children
      and adolescents with acute lymphoblastic leukemia (ALL) in first or second marrow
      relapse were randomly assigned to receive either simultaneous (n = 11) or
      sequential (n = 12) continuous infusions of MTX and VM-26 prior to reinduction.
      Infusions of VM-26 were begun 12 hours after completion of MTX infusion in the
      sequential group. Dosages were individually adjusted to maintain plasma
      concentration levels of 10 microns for MTX and 15 microns for VM-26; total
      infusion times were 24 and 72 hours, respectively. Significant toxicity in the
      first six patients who received the scheduled 72-hour VM-26 infusion (including
      one drug-related death) prompted a 50% reduction in infusion duration. The
      reduced dose was associated with similar but more manageable toxicity.
      Examination of bone marrow aspirates 10 days after therapy was begun showed one
      complete and two partial marrow remissions; a fourth patient who had an aplastic
      marrow on day 10 received no further chemotherapy and had a complete remission
      (CR) documented on day 31. There was no obvious clinical advantage associated
      with either infusion schedule, although small sample sizes preclude definitive
      conclusions. The 17% response rate to the MTX/VM-26 therapeutic window in
      patients with refractory disease suggests the need for further investigation to
      evaluate alternative schedules and concomitant therapy for this drug combination.

PMID- 1985164
TI  - Comparison of neuropsychologic functioning and clinical indicators of
      neurotoxicity in long-term survivors of childhood leukemia given cranial
      radiation or parenteral methotrexate: a prospective study.
AB  - We prospectively compared neuropsychologic functioning and clinical indicators of
      neurotoxicity in 49 consecutive childhood leukemia patients in long-term
      continuous complete remission (CR) who had received two different regimens of CNS
      prophylaxis by random assignment. Twenty-three patients were treated with 1,800
      cGy cranial radiation and intrathecal methotrexate (RT group) and 26 with
      parenteral methotrexate only (MTX group). Over half of the RT group had
      somnolence syndrome, and four developed cerebral calcifications late in their
      clinical course. Abnormal electroencephalograms (EEGs) were seen in 15 patients
      in the MTX group, and six had early, transient white-matter hypodensities
      apparent on computed tomographic (CT) scans. Mean scores on standard tests of
      intelligence and academic achievement, administered after remission induction and
      again at a median of 6 years after treatment cessation, did not differ
      significantly between the two groups. However, statistically significant
      decreases in overall and verbal intelligence quotients (IQs) and in arithmetic
      achievement were found within both treatment groups. Sixteen of 26 in the MTX
      group and 14 of the 23 in the RT group had clinically important decreases
      (greater than or equal to 15 points) on one or more neuropsychologic measures.
      These changes did not correlate with findings on CT scans, EEGs, or other
      clinical signs of neurotoxicity. We conclude that 1,800 cGy cranial radiation and
      parenteral methotrexate, as used in this study, are associated with comparable
      decreases in neuropsychologic function.

PMID- 1985165
TI  - High-dose chemoradiotherapy supported by marrow infusions for advanced
      neuroblastoma: a Pediatric Oncology Group study.
AB  - We conducted a pilot protocol at seven Pediatric Oncology Group (POG)
      institutions to examine the feasibility, toxicity, and efficacy of using a common
      regimen of high-dose chemoradiotherapy (HD CT/RT) supported by autologous or
      allogeneic marrow infusions in children with metastatic neuroblastoma (NBL) in
      first or second remission. During a 57-month period, we accrued 101 patients. We
      report here results for the 81 who completed treatment at least 2 years ago. The
      HD CT/RT regimen consisted of melphalan 60 mg/m2/d for three doses, and total
      body irradiation (TBI) either 1.5 Gy (n = 27) or 2.0 Gy (n = 54) twice daily for
      six doses. Twenty-three patients also received irradiation consisting of 1.2 Gy
      twice daily for 10 doses to persisting disease sites. Seventy-four were given
      autologous and seven allogeneic marrow, 64 autologous marrows being purged
      immunomagnetically. Fifty-four children were in first complete (CR) or partial
      (PR) remission and 27 in second CR or PR. As of October 1, 1990, follow-up was
      from 32 to 72 months. Forty-seven of these 81 children relapsed, 10 died of
      complications, one of unknown cause, and 23 continue in remission, including 21
      of the 54 treated in first remission, and 16 who completed treatment more than 3
      years ago. The 2-year actuarial event-free survival (EFS) probabilities are first
      CR (CR1) 32% (SE 10%), first PR (PR1) 43% (SE 9%), second CR (CR2) 33% (SE 27%),
      and second PR (PR2) 5% (SE 5%). Probability of EFS correlated with remission
      number (first better than second, P less than .001), with interval from diagnosis
      to HD CT/RT (greater than 9 months better than less than 9 months, P = .055), and
      with TBI dose (12 Gy better than 9 Gy, P = .031). These encouraging results may
      partly reflect selection for this treatment of patients with NBL who have a
      slower disease pace.

PMID- 1985166
TI  - Relationship of tumor-cell ploidy to histologic subtype and treatment outcome in
      children and adolescents with unresectable rhabdomyosarcoma.
AB  - Clinical and histopathologic features are often inadequate for accurate
      prediction of relapse or survival of individual patients with rhabdomyosarcoma
      (RMS). We therefore studied the cellular DNA content (ploidy) of RMS cells in
      relation to histology and response to therapy in 37 patients with unresectable
      tumors. Using flow cytometric techniques, we found that about one third of
      patients had diploid tumor stem lines, regardless of the histologic subtype. In
      the group with abnormal ploidy, a hyperdiploid classification (1.10 to 1.80 times
      the DNA content of normal diploid cells) was exclusively associated with
      embryonal histology (P = .001). By contrast, near-tetraploidy (1.80 to 2.60 times
      the DNA content of normal cells) was strongly associated with alveolar histology
      (P = .001). Thus, in these histologic subtypes of RMS, abnormal ploidy appears to
      arise through different mechanisms. Tumor-cell ploidy had a significant impact on
      survival that was especially apparent in patients with unresectable,
      nonmetastatic (group III) tumors. In this subgroup, hyperdiploidy conferred the
      best prognosis and diploidy the worst (P less than .0001). None of the eight
      patients with diploid tumors survived for more than 18 months. Tumor-cell ploidy
      was the best predictor of treatment outcome for patients with either embryonal (P
      less than .001; relative risk, 25.5) or alveolar (P = .073; relative risk 7.1)
      RMS and contributed significantly after adjustment for disease stage and anatomic
      site. Patients with unresectable diploid RMS have an unacceptably high risk of
      treatment failure, justifying new therapeutic approaches for this distinct
      subgroup.

PMID- 1985167
TI  - Surgico-pathologic staging of neuroblastoma.

PMID- 1985168
TI  - Staging systems in neuroblastoma: which is best?

PMID- 1985169
TI  - Median follow-up in clinical trials.

PMID- 1985170
TI  - Cisplatin-induced atrial fibrillation.

PMID- 1985171
TI  - A phase II clinical trial of carboplatin infusion in high-risk acute
      nonlymphoblastic leukemia.
AB  - Carboplatin (CBDCA) is a second-generation platinum drug that has been shown to
      be useful when used as a continuous infusion in treatment of refractory adult
      leukemia. We report on the effectiveness of continuous infusion CBDCA, 300
      mg/m2/d x 5 days, as evaluated in nine patients with secondary acute
      nonlymphocytic leukemia (ANLL) (seven previous myelodysplastic syndrome and two
      treatment-associated ANLL), three ANLL patients in first relapse, six refractory
      ANLL, and nine patients with blastic phase of chronic myelogenous leukemia (BP
      CML). All patients were considered assessable. The response rate was 44% (eight
      complete remissions [CRs], four partial remissions [PRs]). Median duration of
      postchemotherapy neutropenia was 36 days (range, 18 to 45). Therapy was well
      tolerated, and toxicity was mainly hematologic and nondose-limiting. Despite
      prolonged neutropenia, severe infections were rarely seen, and most patients were
      managed as outpatients. Twelve patients had nausea and vomiting, two had
      symptomatic hypomagnesemia, and one patient showed reversible ototoxicity.
      Because of substantial antileukemic activity and unusual extrahematologic
      toxicity, CBDCA appears to be an effective second-line agent in the treatment of
      ANLL and should be considered for upgrading to first-line treatment regimens.

PMID- 1985172
TI  - How American oncologists treat breast cancer: an assessment of the influence of
      clinical trials.
AB  - The present study was designed to assess the preferred methods of treatment of
      breast cancer by American oncologists, and the impact of clinical trials on their
      practice. We mailed 465 questionnaires to surgical, radiation, or medical
      oncologists. The questionnaire described five hypothetic patients with breast
      cancer, and respondents were asked to select their preferred treatment for each
      patient. For primary breast cancer, most physicians would offer the choice of
      local excision followed by radiation therapy or modified radical mastectomy.
      About 80% of physicians would prescribe adjuvant chemotherapy for a premenopausal
      woman with estrogen receptor-negative, axillary node negative breast cancer, and
      for a postmenopausal woman with estrogen receptor-negative, node-positive
      disease. This policy was favored by male and female physicians of each specialty.
      Almost all respondents would treat a young woman with inflammatory breast cancer
      with initial chemotherapy followed by radiation and/or surgery, and about 60%
      would recommend chemotherapy to a postmenopausal patient with estrogen receptor
      negative disease and minimally symptomatic bone metastases. Clinical trials have
      compared treatment strategies that could be applied to patients described in our
      questionnaire. Preferred treatments for primary breast cancer, and for
      inflammatory breast cancer are supported by the results of clinical trials.
      Recommendation of adjuvant chemotherapy for node-negative breast cancer is not
      based on a consistent demonstration of improvement in survival, although
      randomized trials with short follow-up have shown delay to recurrence.
      Recommendation of adjuvant chemotherapy for a postmenopausal woman with node
      positive breast cancer is contrary to the results of large randomized controlled
      trials (and to a meta-analysis), which have shown that this policy does not lead
      to improved survival. Our report suggests that even large randomized clinical
      trials may have a minimal impact on practice if their results run counter to
      belief in the value of the treatment.

PMID- 1985174
TI  - Reading between the lines.

PMID- 1985173
TI  - 4-Hydroperoxycyclophosphamide purging of breast cancer from the mononuclear cell
      fraction of bone marrow in patients receiving high-dose chemotherapy and
      autologous marrow support: a phase I trial.
AB  - We designed an ex vivo bone marrow treatment for breast cancer patients receiving
      high-dose chemotherapy and autologous bone marrow support (ABMS), using 4
      hydroperoxycyclophosphamide (4-HC), an active derivative of cyclophosphamide with
      known activity against breast cancer. This phase I bone marrow purging trial used
      ficoll-separated mononuclear cells (MNC) (devoid of granulocytes and RBCs), as
      opposed to the buffy coat. Twenty-five patients with metastatic breast cancer
      were studied. Patients received three cycles of the Adriamycin (doxorubicin;
      Adria Laboratories, Columbus, OH), fluorouracil, and methotrexate (Duke AFM)
      regimen, followed by marrow harvest. An MNC fraction of marrow was prepared and
      treated with 4-HC in concentrations of 20 micrograms/mL (four patients), 40
      micrograms/mL (four patients), 60 micrograms/mL (nine patients), or 80
      micrograms/mL (eight patients) and cryopreserved. Patients then received high
      dose systemic cyclophosphamide, cisplatin, and carmustine, followed by infusion
      of the purged marrow. The study end point was marrow engraftment, defined as WBC
      count greater than 1,000 cells per microliter. At the first three dose levels
      (20, 40, and 60 micrograms/mL 4-HC), there was no significant delay in time to
      engraftment (19, 20, and 23 days, respectively) compared with the unpurged
      historical controls (17 days). At 80 micrograms/mL, engraftment was significantly
      delayed compared with the lower concentrations (P = .027), and further escalation
      of 4-HC was not attempted. A significant correlation was observed between the
      time of leukocyte engraftment and the 4-HC concentration (P = .017). With a
      methylcellulose-based tissue culture assay, we demonstrated a statistically
      significant correlation between the colony-forming unit-granulocyte-macrophage
      (CFU-GM) content in the purged marrow and the days to engraftment. Ninety-five
      percent of patients responded clinically to the entire program, 55% of them
      completely. Longer follow-up is required to assess the ultimate benefit of
      intensive therapy on long-term survival.

PMID- 1985175
TI  - Avoiding the sagittal sinus during calvarial bone harvest.

PMID- 1985176
TI  - Sleeping or working during residency education?

PMID- 1985177
TI  - Lag screw fixation of anterior mandibular fractures.
AB  - A technique of applying lag screws for treating fractures of the anterior
      mandible is presented. A review of 41 patients who had lag screws placed to treat
      such fractures showed that it is a successful method of providing rigid internal
      fixation. The advantages of this technique over bone-plate fixation are
      discussed.

PMID- 1985179
TI  - The Gillies method for fractured zygomas: an analysis of 105 cases.
AB  - This prospective study analyzed 105 cases treated using the Gillies temporal
      approach for fractures of the zygoma. In 97 cases (92%) this was sufficient. Only
      eight cases required open reduction. It is suggested that the Gillies method be
      used more frequently, because it is associated with minimal morbidity and a short
      duration of general anesthesia.

PMID- 1985178
TI  - Maintenance of condyle-proximal segment position in orthognathic surgery.
AB  - Twenty patients underwent bilateral sagittal ramus osteotomy for the correction
      of mandibular retrognathia. A condylar positioning device (CPD) was used
      intraoperatively in 10 patients to maintain preoperative condyle-proximal segment
      position, while the CPD was not used in the other 10 patients. Postoperatively,
      the condyle-proximal segment positions in both groups were compared and evaluated
      for vertical, horizontal, and rotational changes. A significant improvement (P
      less than .05) was observed in the vertical and horizontal condylar position in
      the group in which the CPD was used. However, there was no significant difference
      in proximal segment rotation.

PMID- 1985180
TI  - Esthetic evaluation and treatment of the upper one third of the face.
AB  - Esthetic assessment and treatment planning for the upper one third of the face is
      reviewed. The importance of esthetic anatomy in evaluation of the face as a whole
      is stressed. Three basic approaches to the forehead and brow lift are discussed,
      with particular regard to patient selection, indications, and contraindications.
      Clinical cases are presented as examples.

PMID- 1985181
TI  - Extraoral application of osseointegrated implants.
AB  - The use of osseointegrated implants to provide support for craniofacial
      prostheses has provided the clinician with another approach to the treatment of
      complex craniofacial reconstructive problems. The surgical technique is reviewed
      and the Mayo Clinic experience is presented.

PMID- 1985182
TI  - A preliminary report of arthroscopic findings following acute condylar trauma.
AB  - Standard therapy in orthopedics dictates that joints with suspected hemarthrosis
      be considered for irrigation or exploration, especially when immobilization is
      part of the treatment plan. In this preliminary report, 14 patients who had
      condylar/subcondylar fractures underwent superior joint space arthroscopy as part
      of the evaluation and treatment of their fractures. In all but two patients,
      blood was found in the superior joint space. Length of time from injury to time
      of examination correlated with the quantities of blood found. The severity and
      direction of the blow seemed to influence the findings in the joints. Synovial
      ecchymosis was a consistent finding. The disc appeared to be grossly intact and
      within the glenoid fossa in all cases, even when the condyle was grossly
      displaced. These findings raise questions about the role of direct disc injury as
      a source of postoperative temporomandibular joint (TMJ) symptoms, as well as
      about the practice of immobilization of fractures immediately after trauma.
      Further studies will be necessary to compare the treatment results in patients
      who have had arthroscopy versus those who have not.

PMID- 1985183
TI  - Care of the asthmatic oral and maxillofacial surgery patient.
AB  - It is estimated that asthma affects 6 to 9 million people in the United States.
      The nature of this disease makes it a special concern to the oral and
      maxillofacial surgeon. Appropriate management of the asthmatic patient with
      regard to anesthesia and surgical procedures of the oral and maxillofacial region
      is discussed.

PMID- 1985184
TI  - Keeping dentistry our home.

PMID- 1985185
TI  - Metastatic endometrial carcinoma to the mandible: a case report.

PMID- 1985186
TI  - Primary mucoepidermoid carcinoma of Stensen's duct.

PMID- 1985187
TI  - Hydatid cyst of the pterygopalatine fossa.

PMID- 1985188
TI  - Osteomyelitis of the coronoid process secondary to chronic mandibular third molar
      pericoronitis.

PMID- 1985189
TI  - Magnetic resonance imaging and tomographic evaluation of occlusal appliance
      treatment for advanced internal derangement of the temporomandibular joint.
AB  - This study evaluates the positional relationship of the disc and mandibular
      condyle in patients with late opening clicks treated with appliance therapy. A
      total of 30 joints (18 patients) were studied. Twenty-seven of these 30 joints
      were treated with the appliance until the joints were silent to auscultation. The
      patients were then evaluated with axial corrected tomography and magnetic
      resonance imaging (MRI) in the centric occlusion position and with their bite
      appliance (Sved-type) in place. Comparisons were made between condyle position in
      centric occlusion and with the appliance in place. Magnetic resonance imaging was
      then used to evaluate disc positional changes. Each imaging procedure was made in
      the same sagittal plane. Only changes in condyle positioning could be identified.
      Evidence of disc repositioning with the appliance in place was seen in only three
      MRI examinations. The remaining 27 joints continued to exhibit disc displacement
      with various changes in disc morphology. It is concluded that the concept of
      "disc capture" is a clinical term only, and that such perceived clinical success
      should not lead to the assumption that an actual change in intra-articular
      anatomic relationships has occurred. Joint noises may decrease because joint
      space is increased, allowing smoother condylar translation beyond disc surface
      irregularities and positional abnormalities.

PMID- 1985190
TI  - Odontogenic myxoma: report of a case with peculiar features.

PMID- 1985191
TI  - A case of desmoplastic variant of a mandibular ameloblastoma.

PMID- 1985192
TI  - Pterygomaxillary separation without the use of an osteotome.

PMID- 1985193
TI  - Conversion of Friend mink cell focus-forming virus to Friend spleen focus-forming
      virus by modification of the 3' half of the env gene.
AB  - The 3' half of the env gene of the dualtropic Friend mink cell focus-forming
      virus was modified by replacing the restriction enzyme fragment of the genome DNA
      with the corresponding fragment of the acutely leukemogenic, polycythemia
      inducing strain of Friend spleen focus-forming virus (F-SFFVP) genome DNA.
      Replacement with the fragment of F-SFFVP env containing the 585-bp deletion, the
      6-bp duplication, and the single-base insertion converted the resulting chimeric
      genome so that the mutant had a pathogenic activity like that of F-SFFVP.
      Replacement with the fragment containing only the 585-bp deletion did not result
      in a pathogenic virus. However, when this virus pseudotyped by Friend murine
      leukemia virus was passaged in newborn DBA/2 mice, we could recover weakly
      pathogenic viruses with a high frequency. Molecular analysis of the genome of the
      recovered virus revealed the presence of a single-base insertion in the same T5
      stretch where the wild-type F-SFFV env has the single-base insertion. These
      results provided evidence that the unique genomic structures present in the 3'
      half of F-SFFV env are the sole determinants that distinguish the pathogenicity
      of F-SFFV from that of Friend mink cell focus-forming virus. The importance of
      the dualtropic env-specific sequence present in the 5' half of F-SFFV env for the
      pathogenic activity was evaluated by constructing a mutant F-SFFV genome in which
      this sequence was replaced by the ecotropic env sequence of Friend murine
      leukemia virus and by examining its pathogenicity. The results indicated that the
      dualtropic env-specific sequence was essential to pathogenic activity.

PMID- 1985194
TI  - Internally located cleavable signal sequences direct the formation of Semliki
      Forest virus membrane proteins from a polyprotein precursor.
AB  - The proteolytic processes involved in the cotranslational production of the
      Semliki Forest virus proteins p62, 6K, and E1 from a common precursor polypeptide
      were analyzed by an in vitro translation-translocation assay. By studying the
      behavior of wild-type and mutant variants of the polyprotein, we show that the
      signal sequences responsible for membrane translocation of the 6K and E1 proteins
      reside in the C-terminal regions of p62 and 6K, respectively. We present evidence
      suggesting that the polyprotein is processed on the luminal side by signal
      peptidase at consensus cleavage sites immediately following the signal sequences.
      Our results also lead us to conclude that the 6K protein is a transmembrane
      polypeptide with its N terminus on the luminal side of the membrane (type I).
      Thus, the production of all three membrane proteins is directed by alternating
      signal and stop-transfer (anchor) sequences that function in translocation and
      cleavage of the virus precursor polyprotein. This also shows conclusively that
      internally located signal sequences can be cleaved by signal peptidase.

PMID- 1985195
TI  - Expression of yeast L-A double-stranded RNA virus proteins produces derepressed
      replication: a ski- phenocopy.
AB  - The plus strand of the L-A double-stranded RNA virus of Saccharomyces cerevisiae
      has two large open reading frames, ORF1, which encodes the major coat protein,
      and ORF2, which encodes a single-stranded RNA-binding protein having a sequence
      diagnostic of viral RNA-dependent RNA polymerases. ORF2 is expressed only as a
      Gag-Pol-type fusion protein with ORF1. We have constructed a plasmid which
      expresses these proteins from the yeast PGK1 promoter. We show that this plasmid
      can support the replication of the killer toxin-encoding M1 satellite virus in
      the absence of an L-A double-stranded RNA helper virus itself. This requires ORF2
      expression, providing a potential in vivo assay for the RNA polymerase and single
      stranded RNA-binding activities of the fusion protein determined by ORF2. ORF1
      expression, like a host ski- mutation, can suppress the usual requirement of M1
      for the MAK11, MAK18, and MAK27 genes and allow a defective L-A (L-A-E) to
      support M1 replication. These results suggest that expression of ORF1 from the
      vector makes the cell a ski- phenocopy. Indeed, expression of ORF1 in a wild-type
      killer makes it a superkiller, suggesting that a target of the SKI antiviral
      system may be the major coat protein.

PMID- 1985197
TI  - Identification of the principal neutralizing determinant of human
      immunodeficiency virus type 1 as a fusion domain.
AB  - The V3 loop, located near the middle of the surface envelope glycoprotein gp120,
      is the major neutralizing domain of human immunodeficiency virus type 1 (HIV-1).
      Although the majority of the V3 loop is highly variable between different strains
      of HIV-1, a Gly-Pro-Gly-Arg motif at the tip of the loop is highly conserved. To
      determine whether this region plays a role in fusion mediated by the HIV-1
      envelope glycoproteins, we introduced seven single-amino-acid changes in the V3
      loop. The mutant envelope glycoproteins were expressed from an HIV-1 envelope
      expression vector and analyzed for their ability to induce cell fusion in the
      absence of virus replication. Our results indicated that single-amino-acid
      changes in the V3 loop were capable of completely abolishing or greatly reducing
      the ability of the HIV-1 envelope glycoproteins to induce cell fusion, thereby
      identifying the V3 loop as a fusion domain of HIV-1. Mutations in the highly
      conserved tip of the loop or in a nonconserved region flanking the highly
      conserved tip had no effect on envelope glycoprotein synthesis, processing,
      transport, or binding to the CD4 receptor molecule. Mutation of the putative
      disulfide bridge-forming Cys at residue 336 blocked gp160 cleavage and CD4
      binding.

PMID- 1985196
TI  - Structural elements that regulate pp59c-fyn catalytic activity, transforming
      potential, and ability to associate with polyomavirus middle-T antigen.
AB  - Except for its unique amino-terminal region (residues 1 through 83), which
      possibly dictates substrate recognition, pp59c-fyn bears a high degree of
      homology with other members of the src family of tyrosine kinases. Here we show
      that the carboxy terminus of pp59c-fyn is necessary for stable middle-T-antigen
      association, that pp59c-fyn is normally phosphorylated on both serine and
      tyrosine residues, and that Tyr-531 and Tyr-420 are phosphorylation sites in vivo
      and in vitro, respectively. Analysis of a spontaneously generated mutant encoding
      a truncated form of pp59c-fyn and of variants specifically mutated at the Tyr-531
      and Tyr-420 phosphorylation sites indicates that pp59c-fyn has regulatory
      elements analogous to those that have already been identified for other src-like
      tyrosine kinases. However, further examination of the pp59c-fyn variants suggests
      the likelihood of additional means by which its activities might be regulated.
      Although alteration of Tyr-531 to phenylalanine (531F) in pp59c-fyn results in a
      protein which is more active enzymatically that the wild type, the enhancement is
      much less than that for the analogous variant of pp60c-src. Furthermore, contrary
      to results of similar experiments on other src-like proto-oncogene products, 531F
      did not induce transformation of NIH 3T3 cells. Studies involving pp59c-fyn-pp60c
      src chimeras in which the unique amino-terminal sequences (residues 1 through 83)
      of the two kinases were precisely interchanged implied that the inability of 531F
      to induce transformation is probably not caused by the absence of substrates for
      pp59c-fyn in NIH 3T3 cells but rather by the insufficient enhancement of pp59c
      fyn kinase activity. It is therefore probable that the kinase and transforming
      activities of pp59c-fyn are repressed by additional regulatory elements possibly
      located in the amino-terminal half of the molecule.

PMID- 1985198
TI  - Evolution of human immunodeficiency virus type 1 nef and long terminal repeat
      sequences over 4 years in vivo and in vitro.
AB  - The evolution of an 851-bp segment of the human immunodeficiency virus type 1
      (HIV-1) genome encoding the nef open reading frame and U3/R elements of the long
      terminal repeat has been followed over a 4-year period in vivo and in vitro. The
      population of viral sequences at any given time was established by sequencing
      cloned polymerase chain reaction products. The samples studied were derived from
      the same man for whom a detailed analysis of the tat gene was previously
      described (A. Meyerhans, R. Cheynier, J. Albert, M. Seth, S. Kwok, J. Sninsky, L.
      Morfeldt-Manson, B. Asjo, and S. Wain-Hobson, Cell 58:901-910, 1989). Once again
      in vitro culture resulted in the selection of minor forms. Over a 4-year period
      in vivo, there was no obvious selection for, or outgrowth of, any particular nef
      or U3/R sequence. Few defective nef protein sequences were observed, which argues
      against nef acting as a negative regulatory factor. Although no functionally
      defective promoter/trans-activation-responsive elements were identified, the
      transactivation efficiencies varied between 0.2 and 2 times that of the control.
      The sequence encoding the most efficient trans-activation-responsive region did
      not outgrow others. The extreme genetic heterogeneity of the different samples of
      the locus, either in vivo or in vitro, indicates that there is no such thing as a
      single, distinct HIV sequence. It is suggested that different HIV-1 loci evolve
      independently, recombination being responsible for their uncoupling.

PMID- 1985200
TI  - Two signals mediate nuclear localization of influenza virus (A/WSN/33) polymerase
      basic protein 2.
AB  - Polymerase basic protein 2 (PB2), a component of the influenza virus polymerase
      complex, when expressed alone from cloned cDNA in the absence of other influenza
      virus proteins, is transported into the nucleus. In this study, we have examined
      the nuclear translocation signal of PB2 by making deletions and mutations in the
      PB2 sequence. Our studies showed that two distant regions in the polypeptide
      sequence were involved in the nuclear translocation of PB2. In one region, four
      basic residues (K-736 R K R) played a critical role in the nuclear translocation
      of PB2, since the deletion or mutation of these residues rendered the protein
      totally cytoplasmic. However, seven residues (M K R K R N S) of this region,
      including the four basic residues, failed to translocate a cytoplasmic reporter
      protein into the nucleus, suggesting that these sequences were necessary but not
      sufficient for nuclear translocation. Deletion of another region (amino acids 449
      to 495) resulted in a mutant protein which was cytoplasmic with a perinuclear
      distribution. This novel phenotype suggests that a perinuclear binding step was
      involved prior to translocation of PB2 across the nuclear pore and that a signal
      might be involved in perinuclear binding. Possible involvement of these two
      signal sequences in the nuclear localization of PB2 is discussed.

PMID- 1985199
TI  - Transport of incoming influenza virus nucleocapsids into the nucleus.
AB  - Upon penetration of the influenza virus nucleocapsid into the host cell
      cytoplasm, the viral RNA and associated proteins are transported to the nucleus,
      where viral transcription and replication occur. By using quantitative confocal
      microscopy, we have found that over half of cell-associated nucleoprotein (NP)
      entered the nucleus with a half time of 10 min after penetration into CHO cells.
      Microinjection and immunoelectron microscopy experiments indicated that the NP
      entered the nucleus through the nuclear pore as part of an intact
      ribonucleoprotein (RNP) structure and that its transport was an active process.
      Transport of the incoming RNPs into the nucleus was not dependent on an intact
      microfilament, microtubule, or intermediate filament network. Subsequent to
      penetration, the matrix (M1) protein appeared to dissociate from the RNP
      structure and to enter the nucleus independently of the RNP. We found that 50% of
      penetrated M1 entered the nucleus with a half time of 25 min after penetration
      into CHO cells. Nuclear transport of M1 appeared to occur by passive diffusion.
      Entry of incoming M1 into the nucleus was not a prerequisite for infection.

PMID- 1985201
TI  - Analysis of murine coronavirus surface glycoprotein functions by using monoclonal
      antibodies.
AB  - The murine coronavirus surface glycoprotein gene was expressed as a fusion
      protein in bacteria, and the expressed protein was used to generate S protein
      specific monoclonal antibodies (MAbs). Three of the MAbs, 11F, 30B, and 10G, were
      able to neutralize virus infectivity, and two of them, 11F and 10G, were able to
      block virus-induced, cell-to-cell fusion. The binding sites of the 11F, 30B, and
      10G MAbs were determined by Western immunoblotting and epitope mapping. The 11F
      and 30B MAbs bound to sites located, respectively, between amino acids 33 to 40
      and 395 to 406 in the amino-terminal (S1) subunit of the S protein, and the 10G
      MAb bound to a site located between amino acids 1123 and 1137 in the carboxy
      terminal (S2) subunit. These data define more precisely the interactions between
      the S1 and S2 subunits of the murine coronavirus S protein and provide further
      insights into its structure and function.

PMID- 1985202
TI  - Biological and immunological properties of human immunodeficiency virus type 1
      envelope glycoprotein: analysis of proteins with truncations and deletions
      expressed by recombinant vaccinia viruses.
AB  - The effects of C-terminal and internal deletions on the synthesis, transport,
      biological properties, and antigenicity of the human immunodeficiency virus type
      1 envelope protein were determined. A family of recombinant vaccinia viruses that
      express N-terminal overlapping env proteins of 204, 287, 393, 502 (full-length
      gp120), 635, 747, and 851 (full-length gp160) amino acids was constructed. All of
      the proteins were detected in intra- and extracellular forms which differed in
      the extent of glycosylation. The 747- and 851-amino-acid proteins were cleaved,
      were expressed on the surface of infected cells, and bound CD4. The 635-amino
      acid env protein was cleaved inefficiently, and both the precursor and product
      were secreted, indicating absence of the transmembrane sequence. The 635- as well
      as the 502-amino-acid protein, which was also largely secreted, could still bind
      CD4. Unexpectedly, the 393-amino-acid protein was anchored in the plasma
      membrane, but neither it nor smaller proteins bound to soluble CD4. When amino
      acids at the gp120-gp41 junction were deleted, proteolytic cleavage of gp160 did
      not occur. Nevertheless, gp160 was inserted into the plasma membrane and bound
      soluble CD4. The predominant conserved B-cell epitopes were mapped to gp41 and
      the C terminus of gp120, whereas cytotoxic T-cell epitopes were distributed
      throughout the length of the glycoproteins.

PMID- 1985203
TI  - Minus-strand copies of replicating coronavirus mRNAs contain antileaders.
AB  - The 5' leader sequence on mRNAs of the porcine transmissible gastroenteritis
      coronavirus was determined and found to be 90 nucleotides in length. An
      oligodeoxynucleotide with a sequence from within the leader was used as a probe
      in Northern analysis on RNA from infected cells, and an antileader (a minus
      strand copy of the leader sequence) was shown to be present on all mRNA minus
      strand species. RNase protection analysis showed the antileader to be
      approximately the same length as the leader. The kinetics of antileader
      appearance was the same as that for the appearance of minus-strand RNA species.
      This, along with a demonstration that viral mRNAs become packaged, gives further
      support to the idea that coronavirus mRNAs can undergo replication via subgenomic
      mRNA-length replicative intermediates, and that input mRNAs from infecting
      virions may serve as initial templates for their own replication. In this sense,
      then, coronaviruses behave in part like RNA viruses with segmented genomes.

PMID- 1985204
TI  - Monocytotropic human immunodeficiency virus type 1 (HIV-1) variants detectable in
      all stages of HIV-1 infection lack T-cell line tropism and syncytium-inducing
      ability in primary T-cell culture.
AB  - We previously demonstrated a correlation between the presence of syncytium
      inducing (SI) human immunodeficiency virus type 1 (HIV-1) variants showing
      tropism for cell line H9 and the occurrence of rapid CD4 cell decline and
      progression to AIDS. In contrast, in stable asymptomatic individuals, we detected
      only isolates with low replication rates that were non-syncytium-inducing (NSI)
      and nontropic for the H9 cell line. Here, we investigated the monocytotropism of
      established HIV-1 isolates with a panel of isolates and with biological HIV-1
      clones with distinct phenotypes. Moreover, the prevalence and biological
      phenotypes of monocytotropic HIV-1 variants in the course of HIV-1 infection were
      analyzed in comparative primary isolation studies on peripheral blood lymphocytes
      (PBL) and monocyte-derived macrophages (MDM). In cell-free infection studies with
      MDM from eight blood donors, 13 of 17 NSI isolates but only 4 of 14 SI isolates
      were able to infect MDM. NSI isolates also infected significantly more different
      donors than SI variants (median, 3 of 8 versus 0 of 8). This enhanced
      monocytotropism of NSI isolates was confirmed in experiments with biological HIV
      1 clones with distinct phenotypes recovered from the same donor. To investigate
      the prevalence and biological phenotypes of monocytotropic variants in different
      stages of HIV-1 infection, sequential isolates from peripheral blood mononuclear
      cell samples from nine asymptomatic individuals, five of whom progressed to AIDS
      and seven of whom had a known time of seroconversion, were recovered by
      cocultivation with both PBL and MDM. Monocytotropic variants were obtained from
      37 of 42 time points. All monocytotropic variants were NSI in PBL culture and non
      T-cell-line tropic, even when SI, T-cell-line-tropic HIV-1 variants could be
      recovered from the same patient sample by cocultivation with PBL. We conclude
      that monocytotropic HIV-1 variants mostly have an NSI phenotype in PBL and, in
      contrast to SI variants, are present at all stages of HIV-1 infection. These
      results suggest an important role for monocytotropic variants in the persistence
      of HIV-1 infection.

PMID- 1985205
TI  - Rex transregulation of human T-cell leukemia virus type II gene expression.
AB  - The Rex protein of the human T-cell leukemia virus type II (HTLV-II), Rex-II,
      plays a central role in regulating the expression of the structural genes of this
      retrovirus. Rex-II acts posttranscriptionally by inducing the cytoplasmic
      expression of the incompletely spliced viral mRNAs that encode the Gag and Env
      structural proteins and the enzymes derived from the pol gene. We now define a
      295-nucleotide cis-acting regulatory element within the 3' long terminal repeat
      of HTLV-II that is required for the effects of Rex-II. This Rex-II response
      element (RexIIRE) corresponds to a predicted, highly stable RNA secondary
      structure and functions when present in the sense but not in the antisense
      orientation. The RexIIRE confers responsiveness not only to Rex-II but also to
      the Rex protein of HTLV-I. Deletion and substitution mutagenesis of the RexIIRE
      permitted identification of a small subregion within the larger element
      critically required for Rex-II responsiveness and further suggested that the
      structurally distinct RexIIREs generated from the 5' and 3' long terminal repeats
      of HTLV-II may differentially regulate the cytoplasmic expression of unspliced
      gag-pol and singly spliced env mRNAs. While the Rev protein of human
      immunodeficiency virus type 1 fails to function via the RexIIRE, the Rex-II
      protein, like Rex-I, can functionally replace the Rev protein of human
      immunodeficiency virus type 1 via its interaction with the Rev response element
      (RevRE).

PMID- 1985206
TI  - Binding of SL3-3 enhancer factor 1 transcriptional activators to viral and
      chromosomal enhancer sequences.
AB  - Interactions between SL3-3 enhancer factor 1 (SEF1) proteins and the enhancer of
      the murine leukemia virus SL3-3 were analyzed. SEF1 proteins were found to
      interact with two different DNA sequences within the DNA repeat region of the
      enhancer; these two motifs cooperated in enhancing initiation of transcription in
      T lymphocytes. Using an electrophoretic mobility shift assay, we identified
      nucleotides that are important for the SEF1 binding, and we deduced a sequence,
      5'-TTTGCGGTTA/T-3' with highly improved binding of SEF1 proteins. We show that
      many different SEF1 binding sequences exist in the transcription control regions
      of different viral and cellular genes. The results indicate a general role of
      SEF1 proteins in T-cell gene expression.

PMID- 1985207
TI  - Structural and functional analysis of the human immunodeficiency virus type 2 Rev
      protein.
AB  - The Rev proteins of the human immunodeficiency virus (HIV) are necessary for
      expression of viral structural gene products. Site-directed mutations were made
      within the HIV-2 rev gene to identify functional domains. We observed that
      similar to HIV-1 Rev, the HIV-2 Rev protein was phosphorylated, albeit to a much
      lesser extent than was HIV-1 Rev. We also found that like HIV-1 Rev, HIV-2 Rev
      localized to the nucleus, with a marked accumulation in the nucleolus. Mutations
      within a stretch of basic residues prevented both nuclear and nucleolar
      localization. Furthermore, mutant Rev proteins able to localize in the nucleus
      but unable to localize in the nucleolus were nonfunctional.

PMID- 1985208
TI  - Induction of high-titer neutralizing antibodies, using hybrid human
      immunodeficiency virus V3-Ty viruslike particles in a clinically relevant
      adjuvant.
AB  - The localization of neutralization determinants within the envelope glycoproteins
      of human immunodeficiency virus (HIV) has been largely achieved by immunizing
      small animals in conjunction with Freund's adjuvant. However, for eventual use in
      humans, candidate HIV vaccine components must also be efficacious in a nontoxic
      formulation. We describe here the production of hybrid Ty viruslike particles
      carrying the major neutralizing domain of HIV and demonstrate the induction of
      high-titer virus-neutralizing antibodies and an HIV-specific T-cell proliferative
      response after immunization in conjunction with aluminum hydroxide. As aluminum
      hydroxide and aluminum phosphate are the only adjuvants currently licensed for
      use in humans, these observations have implications for the development of an
      effective vaccine against HIV.

PMID- 1985210
TI  - The Sfpi-1 proviral integration site of Friend erythroleukemia encodes the ets
      related transcription factor Pu.1.
AB  - Previous studies identified a common site (Sfpi-1) for proviral integration in
      immortalized Friend erythroleukemias. cDNAs corresponding to a 1.5-kb Sfpi-1 mRNA
      were isolated and sequenced. These were larger than an independently isolated
      Sfpi-1 cDNA described by researchers from another laboratory, and they contained
      common differences from that sequence, including in the coding region four extra
      nucleotides that altered the reading frame. The properly translated protein is
      identical to Pu.1, a transcription activation factor that is related to the ets
      oncogene family. Genetic methods were used to map Sfpi-1 with respect to other
      loci on mouse chromosome 2. Our results suggest that Pu.1 blocks erythroblast
      differentiation and thereby causes immortalization.

PMID- 1985209
TI  - Atypical dissemination of the highly neurotropic Borna disease virus during
      persistent infection in cyclosporine A-treated, immunosuppressed rats.
AB  - In adult rats infected with Borna disease virus, the virus was found exclusively
      in the brain, whereas in cyclosporine A-treated rats, infectious virus was also
      detected in peripheral nerve fibers and, unexpectedly, in adjacent organ-specific
      cells. In contrast to untreated virus-infected rats, no major histocompatibility
      complex class II expression was found in the brain of cyclosporine A-treated
      animals.

PMID- 1985211
TI  - Inhibition of human immunodeficiency virus type 1 replication in human T cells
      stably expressing antisense RNA.
AB  - Human T-lymphoid cell lines with constitutive intracellular expression of
      antisense RNA complementary to a 407-bp sequence of the 5' leader-gag region of
      human immunodeficiency virus type 1 were established by using a nonretroviral
      expression vector. In cell lines with antisense RNA expression detectable by
      Northern (RNA) hybridization, human immunodeficiency virus type 1 replication was
      inhibited to 88% 10 days postinfection and this inhibition lasted 3 weeks
      postinfection.

PMID- 1985213
TI  - The 32-kilodalton envelope protein of vaccinia virus synthesized in Escherichia
      coli binds with specificity to cell surfaces.
AB  - The nature of interaction between vaccinia virus and the surface of host cells as
      the first step in virus infection is undefined. A 32-kDa virus envelope protein
      has been identified as a cell surface binding protein (J.-S. Maa, J. F.
      Rodriguez, and M. Esteban, J. Biol. Chem. 265:1569-1577, 1990). To carry out
      studies on the structure-function relationship of this protein, the 32-kDa
      protein was obtained from Escherichia coli cells harboring the expression plasmid
      pT7Ek32. The recombinant polypeptide was found to have structural properties
      similar to those of the native virus envelope protein. Binding studies of 125I
      labeled 32-kDa protein to cultured cells of various origins revealed that the E.
      coli-produced 32-kDa protein exhibited selectivity, specificity, and
      saturability. Scatchard analysis indicated about 4.5 x 10(4) sites per cell with
      a high affinity (Kd = 1.8 x 10(-9) M), suggesting interaction of the 32-kDa
      protein with a specific receptor. The availability of large quantities of the 32
      kDa virus protein in bacteria will permit further structural and functional
      studies of this virus envelope protein and facilitate identification of the
      specific cell surface receptor.

PMID- 1985212
TI  - Vaccinia virus preferentially enters polarized epithelial cells through the
      basolateral surface.
AB  - The uptake of vaccinia virus in polarized epithelial cells was studied to
      determine whether the site of entry was confined to either the apical or the
      basolateral membrane. Virus infection was monitored with a recombinant vaccinia
      virus carrying the luciferase reporter gene. Using cell lines MDCK and MDCK-D11,
      a clonal line with high transepithelial electrical resistance, we determined that
      vaccinia virus preferentially enters through the basolateral membrane. The
      possibility that there is a polarized cell surface distribution of vaccinia virus
      receptors which may be involved in systemic poxvirus infections is discussed.

PMID- 1985214
TI  - Comparison of the transcriptional activity of the long terminal repeats of simian
      immunodeficiency viruses SIVmac251 and SIVmac239 in T-cell lines and macrophage
      cell lines.
AB  - The U3 regions of the long terminal repeats (LTRs) of simian immunodeficiency
      viruses SIVmac251 and SIVmac239 were analyzed for basal transcriptional activity
      and for interaction with cellular factors in the T-cell line HUT-78 and the
      monocyte/macrophage cell line U937. A number of 5' deletions and mutations were
      made in the U3 regions of the two LTRs, and these constructs were placed upstream
      of a plasmid containing the bacterial chloramphenicol acetyltransferase reporter
      gene. The nucleotide sequences between -225 and +18 were sufficient to maintain
      full transcriptional activity of both LTRs in HUT-78 and U937 cells. Nucleotide
      sequence analysis revealed several differences between SIVmac251 and SIVmac239
      within this region. Analysis of deletion mutants revealed that an additional
      removal of bases, from -124 to -225, had little effect on the transcriptional
      activity of the clone 239 LTR, whereas this deletion resulted in a significant
      reduction of activity in the clone 251 LTR. DNase protection assays using nuclear
      extracts from HUT-78 and U937 cells showed that bases within this region bound
      cellular factors. In addition, the NF-kappa B site was protected in DNase assays
      with HUT-78 cells and 12-O-tetradecanoylphorbol-13-acetate-treated U937 cells. An
      additional DNase footprint was detected in SIVmac239, at -52 to -38, just
      upstream of the TATA box. This site overlaps the 3' half of the 3'-most Sp-1 site
      and is downstream of 11 bases that are found in SIVmac239 but not SIVmac251.
      Thus, differences in the sequences in the U3 region of the LTRs of SIVmac251 and
      SIVmac239 have been identified which appear to alter the transcriptional activity
      of these promoters as well as changing the interaction of cellular proteins with
      sequences in the LTRs.

PMID- 1985216
TI  - Biological basis of rabies virus neurovirulence in mice: comparative pathogenesis
      study using the immunoperoxidase technique.
AB  - The CVS strain of fixed rabies virus causes acute, fatal encephalomyelitis in
      young adult ICR mice. Variant RV194-2, which was selected from CVS virus in cell
      culture with a neutralizing antiglycoprotein monoclonal antibody, has a single
      amino acid change in the glycoprotein. The infections caused by CVS virus and
      RV194-2 virus were compared in mice for 14 days postinoculation of 5 x 10(7) PFU
      into the right masseter muscle. All CVS virus-infected mice died (mean time to
      death, 7.9 days), compared with a mortality rate of 8.5% for RV194-2 virus
      infected mice. RV194-2 virus spread to the ipsilateral trigeminal ganglion during
      the first 2 days postinoculation, and both viruses spread to the ipsilateral
      motor nucleus of the trigeminal nerve in the pons. Both viruses spread
      centrifugally and caused infection of bilateral trigeminal ganglia on day 3. The
      viruses spread throughout the central nervous system (CNS) at similar rates, but
      CVS virus infected many more neurons than did RV194-2 virus. Rabies virus antigen
      was observed in only occasional CNS neurons after day 6 of RV194-2 virus
      infection. By this time, CVS virus had caused severe widespread infection. In
      this model, virulence depends on improved efficiency of viral spread between CNS
      neurons rather than the rate of spread or topographical distribution of the
      infection.

PMID- 1985215
TI  - Gene transfer into human lymphocytes by a defective human immunodeficiency virus
      type 1 vector.
AB  - Human immunodeficiency virus type 1 (HIV-1) proviruses containing deletions
      between nucleotides 301 and 319 express viral proteins but exhibit marked
      attenuation in the packaging of viral RNA into virions (A. Lever, H. Gottlinger,
      W. Haseltine, and J. Sodroski, J. Virol. 63:4085-4087, 1989; A. Aldovini and R.
      A. Young, J. Virol. 64:1920-1926, 1990). Here we report that such packaging
      defective proviruses can provide trans-acting viral elements required for the
      transfer of a HIV-1 vector to Jurkat human lymphocytes. The transferred vector
      was unable to encode HIV-1 genes, indicating that the long terminal repeats and
      the immediate flanking viral sequences are sufficient for packaging, reverse
      transcription, and integration. The generation of replication-competent viruses
      in this system was reduced to undetectable levels by providing the trans-acting
      viral functions on two separate expression plasmids. This defective retroviral
      vector provides a means of efficiently introducing desired genetic elements, in
      the absence of HIV-1 genes, into HIV-1 target cells.

PMID- 1985217
TI  - Circular DNA of human immunodeficiency virus: analysis of circle junction
      nucleotide sequences.
AB  - During infection of cells by retroviruses, some of the nonintegrated viral DNA
      can be found as a circular form containing two tandem, directly repeated long
      terminal repeats. The nucleotide sequence at the point where the long terminal
      repeats join (the circle junction) can be used to deduce the terminal nucleotides
      of the linear form of the viral DNA. Comparison of the termini of linear viral
      DNA with sequences at the junctions between the integrated provirus and the host
      chromosome has revealed that for most retroviruses 2 bp are removed from each end
      of the linear viral DNA during integration. For human immunodeficiency virus type
      1 (HIV-1), however, sequence considerations involving primer-binding sites had
      suggested that only 1 bp is removed during integration. We obtained the
      nucleotide sequences at the ends of HIV-1 DNA by using the polymerase chain
      reaction to amplify fragments corresponding to the HIV-1 circle junction. Of 17
      clones containing amplified sequences, 10 had identical circle junctions that
      contained an additional 4 bp (GTAC) relative to the integrated provirus. This
      indicates that, as for other retroviruses, 2 bp are removed from each end of the
      linear HIV-1 viral DNA during integration. The remaining seven isolates contained
      insertions or deletions at the circle junction.

PMID- 1985218
TI  - Specificity of retroviral RNA packaging.
AB  - Encapsidation of retroviral RNA has been shown to be dependent on specific cis
      acting signals, in particular, the packaging region (psi) located near the 5' end
      of the retroviral genome. In this report, we show that a 683-base avian extended
      packaging sequence (psi+) derived from Rous sarcoma virus will direct packaging
      of heterologous hygromycin mRNA into avian virions when present at the 3' end of
      the transcript in the sense orientation. However, this packaging is not as
      efficient as the packaging of RNA encoded by a standard avian retroviral vector.
      A quail cell line containing a Rous sarcoma virus mutant, SE21Q1b, produces
      virions which will package endogenous cellular mRNAs randomly, roughly in
      proportion to their intracellular concentrations. We found that viral particles
      from SE21Q1b retain the capacity to specifically encapsidate hygromycin mRNAs
      containing the avian psi+. To determine whether packaging of cellular mRNA would
      occur in other retroviral packaging lines, we assayed virion RNA isolated from
      the retroviral particles produced by avian and murine packaging lines for the
      presence of endogenous cellular mRNAs. Endogenous cellular mRNAs were not found
      randomly packaged into virions produced by any of the packaging lines examined
      except SE21Q1b. Some specific sequences, however, were found packaged into avian
      virions. Endogenous retrovirus-related mink cell focus-inducing murine leukemia
      virus RNAs and 30S viruslike RNAs were found to be efficiently packaged into
      murine virions even in the presence of RNAs containing all cis-acting retroviral
      sequences.

PMID- 1985219
TI  - Transdominant repressors for human T-cell leukemia virus type I rex and human
      immunodeficiency virus type 1 rev function.
AB  - Human T-cell leukemia virus type I (HTLV-I) encodes a 27-kDa trans-acting gene
      product (Rex) which is involved in the regulated expression of transcripts coding
      for the viral structural proteins. We used oligonucleotide-directed mutagenesis
      to generate a series of mutant HTLV-I rex genes. Transient expression experiments
      demonstrated that 3 of 28 mutant proteins are functionally inactive on the
      homologous HTLV-I rex response element, whereas an additional 2 mutant proteins
      are functionally inactive on the heterologous human immunodeficiency virus type 1
      rev response element. One of these mutants is able to suppress the function of
      the wild-type HTLV-I Rex protein in trans on the homologous rex response element
      sequence. Furthermore, all of these mutants are able to inhibit Rex function on
      the heterologous rev response element sequence. Intriguingly, only three of these
      mutants are able to inhibit the human immunodeficiency virus type 1 Rev protein
      in a dominant-negative manner.

PMID- 1985220
TI  - Proteins encoded in the 81.2- to 85.0-map-unit fragment of Autographa californica
      nuclear polyhedrosis virus DNA can be translated in vitro and in Spodoptera
      frugiperda cells.
AB  - We have previously demonstrated that five open reading frames exist in the
      nucleotide sequence of the 81.2- to 85.0-map-unit (m.u.) segment of plaque
      isolate E of Autographa californica nuclear polyhedrosis virus (AcNPV) DNA. The
      corresponding polypeptides are 9.8, 12.1, 36.6, 25.0, and 48.2 kDa in size (C.
      Oellig, B. Happ, T. Muller, and W. Doerfler, J. Virol. 63:1494, 1989), and we
      have investigated whether these proteins can be translated in infected cells. On
      subfragments of this viral DNA segment, mRNAs were selected from AcNPV-infected
      Spodoptera frugiperda insect cells at different times postinfection (p.i.). The
      in vitro translation of these RNAs in a rabbit reticulocyte-derived cell-free
      translation system yielded polypeptides of approximately 10 to 11, 12 to 14, 28,
      36 to 38, and 48 to 50-kDa which were commensurate in size with the theoretically
      expected values. mRNAs for the 28- and 48- to 50-kDa proteins were identified by
      their translation products at 6 h p.i., and mRNAs for the 10- to 11-, 12- to 14-,
      and 36- to 38-kDa proteins were identified by their translation products at 12 h
      p.i. We constructed an AcNPV recombinant which carried in its polyhedrin gene the
      3.9-kbp EcoRI-HindIII (81.8 to 84.8 m.u.) subfragment of the EcoRI J segment.
      Nucleotide sequence determinations revealed that the intact polyhedrin promoter
      lay adjacent to the additional 81.8- to 84.8-m.u. fragment in this recombinant.
      In S. frugiperda cells, which were infected with the recombinant AcNPV, a protein
      of 36 to 38 kDa was detected at 44 h p.i. in larger amounts than after infection
      with the nonrecombinant virus. However, there was no evidence for larger amounts
      of RNA derived from the 81.8- to 84.8-m.u. fragment in recombinant-infected
      cells. Recombinant-infected cells lacked the polyhedrin polypeptide. The
      synthesis of the 36- to 38-kDa polypeptide in recombinant- or AcNPV-E-infected S.
      frugiperda cells could be demonstrated by immunoprecipitation experiments.
      Peculiarly, this polypeptide was present in the cytoplasm as a 64-kDa
      glycoprotein. These data corroborate the notion that at least some of the open
      reading frames encoded in the 81.2- to 85.0-m.u. segment of AcNPV can be
      expressed in S. frugiperda cells.

PMID- 1985221
TI  - Environment adds to challenges facing Desert Shield physicians.

PMID- 1985222
TI  - Kennedy hearings say no more free lunch--or much else--from drug firms.

PMID- 1985223
TI  - Ethics of receiving gifts considered.

PMID- 1985224
TI  - Does advertising influence physicians?

PMID- 1985225
TI  - From the Health Care Financing Administration.

PMID- 1985226
TI  - From the Centers for Disease Control. Multistate outbreak of poisonings
      associated with illicit use of gamma hydroxy butyrate.

PMID- 1985227
TI  - From the Centers for Disease Control. Trends in lung cancer incidence and
      mortality--United States, 1980-1987.

PMID- 1985228
TI  - Patient-initiated laboratory testing: no gatekeeper, no kidding.

PMID- 1985229
TI  - Explaining variations in hospital death rates.

PMID- 1985230
TI  - The military medical system: a poor model for a national health care program.

PMID- 1985231
TI  - Domestic violence: the role of alcohol.

PMID- 1985232
TI  - Aspirin and migraine: what about women?

PMID- 1985234
TI  - Cardiology and the quality of medical practice. The Cardiology Working Group.

PMID- 1985233
TI  - Mechanical restraint use among residents of skilled nursing facilities.
      Prevalence, patterns, and predictors.
AB  - The patterns of and risk factors for mechanical restraint use were determined in
      12 skilled nursing facilities. Restraints were being used for 59% of residents at
      the beginning of the study; 31% of remaining residents were restrained during the
      follow-up year. No facility characteristic was associated with restraint use. The
      resident characteristics independently associated with initiation of restraints
      were older age, disorientation, dependence in dressing, greater participation in
      social activities, and nonuse of antidepressants. Unsteadiness (72%), disruptive
      behavior such as agitation (41%), and wandering (20%) were the most frequently
      cited reasons for initiation of restraints.

PMID- 1985235
TI  - A report of fluorosis in the United States secondary to drinking well water.
AB  - A 54-year-old female resident of Wellston, Okla, was found to have osteosclerosis
      on a routine chest roentgenogram. Subsequent investigation disclosed the cause of
      her osteosclerosis to be fluorosis secondary to the ingestion of well water
      containing 429 mumol/L of fluoride (recommended levels, 11 to 58 mumol/L). Water
      samples were also obtained from the 12 wells on properties adjacent to the index
      case. In three other wells, all at similar depths as the well of the index case,
      the fluoride concentration of the water was greater than 212 mumol/L. Urine
      samples from members of the four households who obtain their drinking water from
      these wells contained elevated urinary fluoride levels. Thus, fluorosis may
      develop in certain areas of the United States as a result of the natural
      occurrence of fluoride in the groundwater. Consequently, in known endemic areas,
      it would appear reasonable to measure the fluoride concentration of the well
      water at the time of drilling.

PMID- 1985236
TI  - Who really determines your patients' prescriptions?

PMID- 1985237
TI  - Gifts to physicians from industry.

PMID- 1985239
TI  - Diagnostic and therapeutic technology assessment. Pancreatic transplantations.

PMID- 1985238
TI  - The other Super Bowl question--can the NFL police its drug policy?

PMID- 1985240
TI  - Exercise-associated urinary incontinence.

PMID- 1985241
TI  - Unexplained rabies in three immigrants in the United States. A virologic
      investigation.
AB  - BACKGROUND: Extensive investigation of three patients who died of rabies in the
      United States failed to reveal any source of exposure to the disease. The three
      patients had immigrated to the United States from areas in Laos, the Philippines,
      and Mexico where rabies is endemic. METHODS: We studied rabies viruses isolated
      from the three patients, other patients with a known source of exposure, and
      animals in the United States, Thailand (as a proxy for Laos), the Philippines,
      and Mexico. The viruses were characterized by indirect immunofluorescence and
      neutralization tests according to their reactions to panels of monoclonal
      antibodies. Transcribed complementary DNA from these isolates was amplified by
      the polymerase chain reaction; the DNA product was then analyzed by differential
      digestion with restriction enzymes. RESULTS: The viral isolate from each of the
      three patients was a rabies variant with distinctive antigenic or genetic
      characteristics. For each of the three isolates, identical variants were found in
      specimens from rabid animals obtained from or near the country in which the
      patient lived before immigrating to the United States. None of these variants
      were found among the isolates collected from rabid animals in the United States.
      CONCLUSIONS: Rabies infection in these three patients did not originate in the
      United States but resulted from exposures in Laos, the Philippines, and Mexico.
      Since the three patients had lived in the United States for 4 years, 6 years, and
      11 months, our findings suggest that the onset of the clinical manifestations of
      rabies occurred after long incubation periods.

PMID- 1985242
TI  - Cancer mortality in workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin.
AB  - BACKGROUND: In both animal and epidemiologic studies, exposure to dioxin (2,3,7,8
      tetrachlorodibenzo-p-dioxin, or TCDD) has been associated with an increased risk
      of cancer. METHODS: We conducted a retrospective cohort study of mortality among
      the 5172 workers at 12 plants in the United States that produced chemicals
      contaminated with TCDD. Occupational exposure was documented by reviewing job
      descriptions and by measuring TCDD in serum from a sample of 253 workers. Causes
      of death were taken from death certificates. RESULTS: Mortality from several
      cancers previously associated with TCDD (stomach, liver, and nasal cancers,
      Hodgkin's disease, and non-Hodgkin's lymphoma) was not significantly elevated in
      this cohort. Mortality from soft-tissue sarcoma was increased, but not
      significantly (4 deaths; standardized mortality ratio [SMR], 338; 95 percent
      confidence interval, 92 to 865). In the subcohort of 1520 workers with greater
      than or equal to 1 year of exposure and greater than or equal to 20 years of
      latency, however, mortality was significantly increased for soft-tissue sarcoma
      (3 deaths; SMR, 922; 95 percent confidence interval, 190 to 2695) and for cancers
      of the respiratory system (SMR, 142; 95 percent confidence interval, 103 to 192).
      Mortality from all cancers combined was slightly but significantly elevated in
      the overall cohort (SMR, 115; 95 percent confidence interval, 102 to 130) and was
      higher in the subcohort with greater than or equal to 1 year of exposure and
      greater than or equal to 20 years of latency (SMR, 146; 95 percent confidence
      interval, 121 to 176). CONCLUSIONS: This study of mortality among workers with
      occupational exposure to TCDD does not confirm the high relative risks reported
      for many cancers in previous studies. Conclusions about an increase in the risk
      of soft-tissue sarcoma are limited by small numbers and misclassification on
      death certificates. Excess mortality from all cancers combined, cancers of the
      respiratory tract, and soft-tissue sarcoma may result from exposure to TCDD,
      although we cannot exclude the possible contribution of factors such as smoking
      and occupational exposure to other chemicals.

PMID- 1985243
TI  - Prognostic value of immunocytologic detection of bone marrow metastases in
      neuroblastoma.
AB  - BACKGROUND: Morphologic evaluation of bone marrow for neuroblastoma cells is a
      routine and important component of clinical staging. Specific immunostaining of
      malignant cells with monoclonal antibodies should be more sensitive, however, and
      may improve the detection of metastases and provide additional prognostic
      information. METHODS: We looked for tumor cells in bone marrow from 197 patients
      with newly diagnosed neuroblastoma, using immunoperoxidase staining with
      monoclonal antibodies (immunocytologic analysis) and examination of smears and
      specimens obtained by trephine biopsy (conventional analysis). RESULTS: Routine
      smears and trephine-biopsy specimens were positive for tumor cells in 46 percent
      of the patients, whereas 67 percent were positive on immunocytologic analysis (P
      less than 0.0001). Immunocytologic analysis detected bone marrow metastases in 34
      percent of patients considered to have only localized or regional disease (Stage
      I, II, or III). It also identified tumor cells that were not detected by
      conventional analysis in patients with widespread disease (Stage IV or IVS).
      Tumor content, as determined by immunocytologic analysis, predicted clinical
      outcome in relation to the age of the patient at diagnosis. Patients with Stage
      II or III disease diagnosed after one year of age who did not have occult marrow
      metastases did well, whereas those with metastases did poorly (P = 0.006).
      Patients in whom Stage IV disease was diagnosed before they were one year of age
      did well if bone marrow metastases were few or absent, but had poor survival if
      the marrow contained more than 0.02 percent tumor cells (P = 0.03). CONCLUSIONS:
      Immunocytologic analysis of bone marrow aspirates is more sensitive than
      conventional analysis in detecting tumor cells and provides prognostic
      information. The relations among marrow metastases, age at diagnosis, and
      clinical outcome illustrate the biologic heterogeneity of neuroblastoma.

PMID- 1985244
TI  - The variability of young children's energy intake.
AB  - BACKGROUND: Research conducted in the 1930s showed that, given nutritious
      choices, children can select an adequate diet without adult supervision.
      Paradoxically, children grew well and were healthy despite patterns of intake at
      individual meals that were unpredictable and highly variable. METHODS: To
      investigate in more detail the energy intake of young children, we measured 24
      hour food intake for 15 children, from two to five years of age, on six days. For
      each of the six days of the study, coefficients of variation were calculated for
      each child for each of the six meals and snacks (breakfast, lunch, dinner, and
      morning, afternoon, and evening snacks) and for total daily energy intake.
      RESULTS: The children's intake at individual meals was highly variable, but total
      daily energy intake was relatively constant for each child. The mean coefficient
      of variation for each child's energy intake at individual meals was 33.6 percent;
      in contrast, the mean coefficient of variation for each child's total daily
      energy intake was 10.4 percent. In most cases, high energy intake at one meal was
      followed by low energy intake at the next meal, or vice versa. CONCLUSIONS:
      Although children's food consumption is highly variable from meal to meal, daily
      energy intake is relatively constant, because children adjust their energy intake
      at successive meals.

PMID- 1985245
TI  - Carcinoma of the prostate.

PMID- 1985246
TI  - A cluster of Pneumocystis carinii pneumonia in adults without predisposing
      illnesses.

PMID- 1985247
TI  - Children and food--order amid chaos.

PMID- 1985248
TI  - Pneumocystis carinii--new clinical spectrum?

PMID- 1985249
TI  - Issues raised by the possible transmission of HIV from a dentist to a patient.

PMID- 1985250
TI  - Zidovudine after occupational exposure to the human immunodeficiency virus.

PMID- 1985251
TI  - Reinjection of thallium after stress-redistribution imaging.

PMID- 1985252
TI  - Narcolepsy.

PMID- 1985253
TI  - Court-ordered cesarean sections.

PMID- 1985254
TI  - Residency training under New York's new regulations.

PMID- 1985255
TI  - Case of a leaking water bed mimicking ruptured fetal membranes.

PMID- 1985256
TI  - Human genetics. The essence of inactivity.

PMID- 1985257
TI  - Embryology. Molecule of the moment.

PMID- 1985258
TI  - Palaeontology. New fossils and primate origins.

PMID- 1985259
TI  - Name dropping.

PMID- 1985260
TI  - Localized sex in bacteria.
AB  - Electrophoretic studies suggest that bacterial populations consist of a number of
      independent clones and that genetic recombination is rare in nature. But DNA
      sequencing reveals that individual bacterial genes have a mosaic structure that
      could have arisen only by recombination. How can these observations be reconciled
      and what is their relevance to prokaryotic evolution?

PMID- 1985262
TI  - Research budget. Growth continues in adversity.

PMID- 1985261
TI  - A gene from the region of the human X inactivation centre is expressed
      exclusively from the inactive X chromosome.
AB  - X-chromosome inactivation results in the cis-limited dosage compensation of genes
      on one of the pair of X chromosomes in mammalian females. Although most X-linked
      genes are believed to be subject to inactivation, several are known to be
      expressed from both active and inactive X chromosomes. Here we describe an X
      linked gene with a novel expression pattern--transcripts are detected only from
      the inactive X chromosome (Xi) and not from the active X chromosome (Xa). This
      gene, called XIST (for Xi-specific transcripts), is a candidate for a gene either
      involved in or uniquely influenced by the process of X inactivation.

PMID- 1985263
TI  - Animal welfare. More monkey business.

PMID- 1985264
TI  - Biotechnology. More problems than products.

PMID- 1985265
TI  - Universities. Battling for and against rising numbers.

PMID- 1985266
TI  - Localization of a human system for sustained attention by positron emission
      tomography.
AB  - Positron emission tomographic (PET) studies of human attention have begun to
      dissect isolable components of this complex higher brain function, including a
      midline attentional system in a region of the anterior cingulate cortex. The
      right hemisphere may play a special part in human attention; neglect, an
      important phenomenon associated with damage to attentional systems, is more
      severe, extensive and long-lasting after lesions to the right hemisphere. Here we
      use PET measurements of brain blood flow in healthy subjects to identify changes
      in regional brain activity during simple visual and somatosensory tasks of
      sustained attention or vigilance. We find localized increases in blood flow in
      the prefrontal and superior parietal cortex primarily in the right hemisphere,
      regardless of the modality or laterality of sensory input. The anterior cingulate
      was not activated during either task. These data localize the vigilance aspects
      of normal human attention to sensory stimuli, thereby clarifying the biology
      underlying asymmetries of attention to such stimuli that have been reported in
      clinical lesions.

PMID- 1985267
TI  - First skulls of the early Eocene primate Shoshonius cooperi and the anthropoid
      tarsier dichotomy.
AB  - The phylogenetic relationships of living tarsiers and extinct omomyid primates
      are critical for deciphering the origin and relationships of primate higher taxa,
      particularly anthropoids. Three competing phylogenetic hypotheses are: (1)
      tarsiers are most closely related to early Cenozoic Omomyidae, particularly
      genera such as Necrolemur from the late Eocene of Europe; (2) tarsiers share a
      more recent common ancestry with anthropoids than they do with any known omomyid;
      (3) tarsiers and/or omomyids are most closely related to strepsirhines. The
      anatomy of four skulls of the early Eocene omomyid Shoshonius cooperi--the first
      cranial material recovered for this genus--strongly suggests that Shoshonius
      shares a more recent common ancestry with Tarsius than do either anthropoids or
      other Eocene omomyids for which cranial anatomy is known. If the primate suborder
      Haplorhini (anthropoids, omomyids, tarsiids) is monophyletic, the phylogenetic
      position of Shoshonius requires that anthropoids and Tarsius diverged by at least
      the early Eocene, some 15 million years before the first appearance of
      anthropoids in the fossil record.

PMID- 1985268
TI  - Decreased osmotic stability of dystrophin-less muscle cells from the mdx mouse.
AB  - Human X-linked Duchenne and Becker muscular dystrophies are due to defects in
      dystrophin, the product of an exceptionally large gene. Although dystrophin has
      been characterized as a spectrin-like submembranous cytoskeletal protein, there
      is no experimental evidence for its function in the structural maintenance of
      muscle. Current hypotheses attribute necrosis of dystrophin-less fibres in situ
      to mechanical weakening of the outer membrane, to an excessive influx of Ca2+
      ions, or to a combination of these two mechanism, possibly mediated by stretch
      sensitive ion channels. Using hypo-osmotic shock to determine stress resistance
      and a mouse model (mdx) for the human disease, we show that functional dystrophin
      contributes to the stability of both cultured myotubes and isolated mature muscle
      fibres.

PMID- 1985269
TI  - Excess beta 2 microglobulin promoting functional peptide association with
      purified soluble class I MHC molecules.
AB  - T lymphocytes expressing alpha beta receptors recognize antigenic peptide
      fragments bound to major histocompatibility complex class I or class II molecules
      present on the surface membranes of other cells. Peptide fragments are present in
      the two available HLA crystal structures and recent data indicate that peptide is
      required for the stable folding of the class I heavy chain and maintenance of its
      association with the class I light chain, beta 2-microglobulin (beta 2m), at
      physiological temperature. To explain how the exogenous peptide used to create
      targets for cytotoxic cells bearing CD8 antigen could associate with apparently
      peptide-filled extracellular class I molecules, we hypothesized that stable
      binding of exogenous peptide to mature class I molecules reflects either the
      replacement of previously bound peptide during the well documented beta 2m
      exchange process or the loading of 'empty' class I heavy chains dependent on the
      availability of excess beta 2m. In either case, free beta 2m should enhance
      peptide/class I binding. Using either isolated soluble class I molecules or
      living cells, we show here that free purified beta 2m markedly augments the
      generation of antigenic complexes capable of T-cell stimulation.

PMID- 1985270
TI  - Localization of the X inactivation centre on the human X chromosome in Xq13.
AB  - X-chromosome inactivation results in the strictly cis-limited inactivation of
      many but not all genes on one of the two X chromosomes during early development
      in somatic cells of mammalian females. One feature of virtually all models of X
      inactivation is the existence of an X-inactivation centre (XIC) required in cis
      for inactivation to occur. This concept predicts that all structurally abnormal X
      chromosomes capable of being inactivated have in common a defineable region of
      the X chromosome. Here we report an analysis of several such rearranged human X
      chromosomes and define a minimal region of overlap. The results are consistent
      with models invoking a single XIC and provide a molecular foothold for cloning
      and analysing the XIC region. One of the markers that defines this region is the
      XIST gene, which is expressed specifically from inactive, but not active, X
      chromosomes. The localization of the XIST gene to the XIC region on the human X
      chromosome implicates XIST in some aspect of X inactivation.

PMID- 1985271
TI  - On the production of neurologists in the United States: an update.
AB  - Based primarily on a survey of all neurology residency training programs in the
      United States conducted in 1985-1986, the average annual production (incidence)
      of general neurologists for 1980-1986 was 363.6 and of child neurologists for
      1982-1986, 53.8. About 1/4 of these general neurologists and 1/3 of child
      neurologists are women; about 1/4 of either are foreign medical graduates,
      predominantly foreign-born. Data routinely published by the AMA well match the
      questionnaire information. First postgraduate year of training was in internal
      medicine for 2/3 of general neurologists. Board certification have recently
      averaged 290.9 (general) and 37.1 (child) per annum. From life-table
      calculations, prevalence of general neurologists in 1990 is estimated at 7,500
      fully-trained and 5,500 board-certified, and of child neurologists near 1,100
      trained and over 600 certified. The number of neurologists is predicted to
      plateau near the year 2020 at some 13,700 trained, including 1,700 child
      neurologists, and 9,800 certified (1,100 child). The maximal prevalence rate for
      all neurologists will be 4.75 per 100,000 population in 2010, declining then to
      4.42 by 2050; those rates provide shortfalls of 30% and 35%, respectively,
      compared with previously calculated needs for neurologists.

PMID- 1985272
TI  - Roy and Sherrington (1890): a centennial reexamination of "On the regulation of
      the blood-supply of the brain".

PMID- 1985273
TI  - Fulminating multiple sclerosis-like leukoencephalopathy revealing human
      immunodeficiency virus infection.
AB  - A 66-year-old French homosexual man and a 42-year-old Brazilian man with no known
      risk factors for HIV infection developed headaches, asthenia, and neurologic
      episodes of abrupt onset. CT showed multiple hypodense, nonenhancing lesions.
      Serology for HIV was positive. They died respectively 2 months and 1 month after
      onset of the illnesses. Autopsy in both cases showed multiple, well-demarcated,
      demyelinating foci in the white matter of the cerebral hemispheres, brainstem,
      and cerebellum with histologic features characteristic of recent plaques of
      multiple sclerosis. There were no multinucleated giant cells or microglial
      nodules. Immunostaining for HIV was negative. Although a random coincidence of MS
      and HIV infection cannot be ruled out, the close temporal relationship between
      the 2 disorders suggests a possible etiologic association.

PMID- 1985274
TI  - Transcranial Doppler in acute hemispheric brain infarction.
AB  - We studied cerebrovascular anatomy using intra-arterial digital angiography, and
      blood flow velocity in the middle cerebral artery (MCA) using transcranial
      Doppler (TCD) ultrasonography in 42 patients with acute hemispheric ischemic
      brain infarction. We compared angiography with TCD and the clinical findings
      within 6 hours of the onset of symptoms. The location and extent of the chronic
      ischemic brain damage was assessed by CT performed 1 to 3 months after the ictus.
      Abnormal TCD, as manifested by either an unobtainable MCA flow signal or a
      significantly depressed MCA flow velocity, was highly associated with proximal
      MCA occlusions demonstrated by angiography. Abnormal TCD predicted both larger
      chronic CT lesions and more extensive ischemic change within the MCA territory.
      These data demonstrate that early TCD conveys useful information concerning
      cerebral tissue prognosis following hemispheric ischemia.

PMID- 1985275
TI  - In vivo muscle magnetic resonance spectroscopy in the clinical investigation of
      mitochondrial disease.
AB  - We have investigated the sensitivity and specificity of a rapid phosphorus
      magnetic resonance spectroscopy (MRS) protocol for detecting metabolic
      abnormalities in vivo in skeletal muscle of patients with mitochondrial disease.
      We examined 17 patients with mitochondrial myopathies. Sixteen had only mild or
      minimal myopathic signs and symptoms. Phosphorus magnetic resonance spectra from
      the resting gastrocnemius muscles showed an abnormal intracellular energy state
      (marked by an increased intracellular inorganic phosphate concentration) in
      14/17. In 3/17, this was associated with a decreased phosphocreatine
      concentration. We also studied 20 patients with other diseases of muscle
      (inflammatory myopathies, metabolic myopathies, muscular dystrophies, and
      myasthenia gravis) that can present with similar clinical features. Spectra
      showed increased intracellular inorganic phosphate concentrations in 6/20. All of
      these muscle diseases were associated with evidence of muscle fiber necrosis.
      Abnormalities in the muscle energy state in these cases may be due to secondary
      mitochondrial dysfunction. Except for cases of polymyositis and dermatomyositis,
      these 6 other myopathies could be readily distinguished from the mitochondrial
      myopathies on the basis of the clinical examination and blood tests. We conclude
      that phosphorus MRS of resting muscle is practical in a clinical setting and has
      a useful sensitivity and specificity for mitochondrial myopathies when used in
      conjunction with standard noninvasive tests.

PMID- 1985276
TI  - Serum and CSF levels of IL-2, sIL-2R, TNF-alpha, and IL-1 beta in chronic
      progressive multiple sclerosis: expected lack of clinical utility.
AB  - We measured interleukin-2 (IL-2), soluble IL-2 receptor (sIL-2R), tumor necrosis
      factor-alpha (TNF-alpha), and interleukin-1 beta (IL-1 beta) by ELISA in paired
      sera and CSF from 50 chronic progressive multiple sclerosis (CPMS) patients
      during worsening disability, 19 patients with other neurologic diseases (OND),
      and in sera from 40 healthy volunteers. In the CPMS patients, 28% (14/50), 10%
      (5/50), 16% (8/50), and 6% (3/50) had elevated serum levels of IL-2, sIL-2R, TNF
      alpha and IL-1 beta, respectively, compared with healthy controls. The only
      analyte we detected in the CSF was IL-2 in 1 CPMS patient (1/50, 2%). We also saw
      elevated serum sIL-2R in 16% (3/19) of OND patients. We found no significant
      difference in mean levels of serum sIL-2R between the 3 groups. Our study, the
      largest to date of CPMS patients, shows that serum and CSF levels of IL-2, sIL
      2R, TNF-alpha, or IL-1 beta are not sensitive for, and the serum sIL-2R level is
      not specific for, CPMS. Therefore, measurement of these analytes will not be
      clinically useful for therapeutic or prognostic purposes in the majority of CPMS
      patients.

PMID- 1985277
TI  - Neonatal subependymal giant cell astrocytoma associated with tuberous sclerosis:
      MRI, CT, and ultrasound correlation.
AB  - We describe a term newborn with tuberous sclerosis who presented with a neonatal
      brain tumor, diagnosed as a subependymal giant cell astrocytoma. We compare the
      various imaging modalities used in the diagnosis of this tumor.

PMID- 1985278
TI  - "Pseudospasticity" in Guillain-Barre syndrome.
AB  - We report a woman with Guillain-Barre syndrome who developed a flexion posture of
      the right arm and hand resembling upper motor neuron dysfunction. EMG
      demonstrated that involuntary peripherally generated continuous motor unit
      discharges caused the posture.

PMID- 1985280
TI  - Handcuff neuropathies.
AB  - Compressive neuropathy due to tight application of handcuffs occurred in 5
      patients. The superficial radial nerve was affected in 8 hands and the median
      nerve in two. Neurologic deficits persisted as long as 3 years after handcuffing.
      Nerve conduction studies helped to exclude malingering and other diagnoses. All
      patients had been intoxicated when handcuffed or had been arrested with force.
      The handcuff mechanism, which allows accidental overtightening after application,
      is an unrecognized factor in these neuropathies.

PMID- 1985279
TI  - Neuropsychological effects of carbamazepine and phenytoin: a reanalysis.
AB  - We previously reported that carbamazepine had fewer adverse neuropsychological
      effects than phenytoin, but it is now clear that our patients had much higher
      phenytoin than carbamazepine serum levels. When persons with high initial
      phenytoin levels were excluded, the statistical significance of all
      neuropsychological differences between the drugs disappeared.

PMID- 1985281
TI  - Brain and spinal cord hemorrhage in long-term survivors of malignant pediatric
      brain tumors: a possible late effect of therapy.
AB  - Three children with malignant primary CNS tumors treated with craniospinal
      radiotherapy developed intraparenchymal hemorrhages a median of 5 years following
      therapy in sites distant from the primary tumor. Radical surgical procedures
      disclosed fresh and old hematoma, gliosis, and necrosis in all 3 patients and an
      aggregation of abnormal microscopic blood vessels in two. No tumor was found. All
      3 patients remain in long-term (greater than 10 years) continuous remission.

PMID- 1985283
TI  - Myelopathic neurosarcoidosis: diagnostic value of enhanced MRI.
AB  - Neurosarcoidosis is an underdiagnosed variant of the systemic disease. We report
      a case of myelopathic neurosarcoidosis, noting the contribution made by MRI in
      establishing the diagnosis, and we discuss the possibility that the disease is
      differentially responsive to various steroid formulations.

PMID- 1985282
TI  - Clinical and magnetic resonance imaging in optic neuritis.
AB  - We found 23 of 48 patients (48%) with isolated monosymptomatic optic neuritis
      (ON) to have 1 to several brain lesions by MRI. All the brain lesions were
      clinically silent and had characteristics consistent with multiple sclerosis
      (MS). During 4 years of follow-up, 9 patients (19%) developed definite MS on
      clinical grounds. Six of the converting patients had abnormal MRIs; the other 3
      had MRIs that were normal both initially (when they had ON only) and when
      repeated after they had developed MS. The other 17 patients with abnormal MRIs
      have not developed symptoms or signs of MS during follow-up. Thus, an abnormal
      MRI does not auger development of clinical MS within a mean of 4 years, nor does
      a normal MRI protect against development of disseminated disease. It is not
      prudent to give a patient with isolated monosymptomatic ON the diagnosis of MS
      (probable or definite) because of an abnormal MRI (with or without other
      laboratory abnormalities).

PMID- 1985284
TI  - Sleep apnea syndrome presenting with cognitive impairment.

PMID- 1985285
TI  - Cranial neuropathy.

PMID- 1985287
TI  - Cost of neurologic care.

PMID- 1985286
TI  - Epidemiology of MS.

PMID- 1985288
TI  - Familial subclinical multiple sclerosis.

PMID- 1985289
TI  - The efficacy of azathioprine in relapsing-remitting multiple sclerosis.
AB  - We randomized 59 patients with relapsing-remitting multiple sclerosis to receive
      azathioprine (AZA) 3.0 mg/kg daily or placebo in a double-masked therapeutic
      trial. Analysis of data for predetermined primary outcome measures demonstrated a
      significant difference favoring AZA for observed mean exacerbation rate after 2
      years of therapy and time to deterioration in both Ambulation Index and Kurtzke
      Expanded Disability Status Scale score. This study confirms a modest therapeutic
      benefit for azathioprine previously reported by other investigators.

PMID- 1985290
TI  - Mesencephalic cholinergic nuclei in progressive supranuclear palsy.
AB  - Using an antibody against choline acetyltransferase (ChAT), mesencephalic
      cholinergic cell nuclei were studied in autopsy material from 3 cases of
      progressive supranuclear palsy (PSP) and 4 controls. ChAT-immunoreactive neurons
      were quantified in sections that spanned the rostrocaudal extent of each nucleus.
      In PSP, there was a significant decrease in the number of neurons with detectable
      immunoreactivity for ChAT in and adjacent to the central gray substance in the
      following nuclei: the nucleus of Edinger-Westphal (69%); the rostral interstitial
      nucleus of the medial longitudinal fasciculus (97%); the interstitial nucleus of
      Cajal (78%). A cell loss was also evident in a group of neurons found in the deep
      layers of the superior colliculus (93%). In contrast, the estimated number of
      ChAT-immunoreactive cell bodies in cranial nerves III and IV, in the
      mesencephalic reticular formation, and in the parabigeminal nucleus was not
      different from that of controls. The results are compatible with the notion that,
      in PSP, there is a regionally selective destruction of cholinergic neurons.

PMID- 1985291
TI  - Absence of highly homologous sequence to HTLV-I in Japanese multiple sclerosis.
AB  - We tried to detect HTLV-I-related sequences in Japanese patients with multiple
      sclerosis with a highly sensitive method that employs the polymerase chain
      reaction (PCR) of genomic DNA followed by Southern blot hybridization analysis.
      To amplify HTLV-I sequences, we used primers for LTR, pol, gag, and env coding
      regions. Fourteen patients with definite MS, 14 disease controls, 12 normal
      controls, and 3 patients with HTLV-I-associated myelopathy (HAM) were
      investigated. Results of particle aggregation assay for HTLV-I antibodies were
      negative in serum from all subjects except for the 3 HAM patients. Neither the 14
      MS patients nor the 26 controls showed the presence of any highly homologous
      sequences to HTLV-I. We did observe faint signals for gag, pol, and env coding
      regions only at low stringent hybridization in some MS patients as well as some
      normal controls. The nucleotide sequence analysis of the faint bands was more
      homologous to major histocompatibility complex molecules than the HTLV-I genome.

PMID- 1985292
TI  - Cerebral atrophy in habitual cocaine abusers: a planimetric CT study.
AB  - We compared cranial CTs of 35 habitual cocaine abusers, 16 self-reported 1st-time
      users, and 54 headache patients using linear planimetric measures. All patients
      met the following criteria: age 20 to 40 years, no polydrug abuse (including
      alcohol), HIV seronegativity, normal albumin level, and no history of any other
      neurologic disease. The sex ratios and ages were not significantly different in
      the 3 groups. The planimetric measurements and calculated indices of cerebral
      atrophy were significantly different in the habitual cocaine abusers compared
      with the 2 other groups of patients. There were no differences between 1st-time
      cocaine users and controls. Among the habitual cocaine abusers there was a
      positive correlation between the approximate duration of cocaine abuse and the
      calculated atrophy indices. The findings suggest that cerebral atrophy develops
      in chronic cocaine abusers, and the severity correlates with the duration of
      abuse.

PMID- 1985293
TI  - The effect of spine fusion on respiratory function in Duchenne muscular
      dystrophy.
AB  - Serial measures of respiratory function were made in 17 patients with Duchenne
      muscular dystrophy who underwent segmental spine fusion and in 22 patients who
      did not. No significant differences were observed between the 2 groups (operated
      vs. nonoperated) in terms of declining respiratory function. Nonetheless, all
      operated patients reported either improved sitting comfort, appearance, or both.
      Thus, our results suggest that there are distinct benefits from segmental spine
      fusion; however, there was no salutary effect upon respiratory function either in
      the short term or after up to 5 years follow-up.

PMID- 1985294
TI  - Central nervous system involvement in Von Hippel-Lindau disease.
AB  - Fifty individuals with Von Hippel-Lindau disease (VHL) were studied with
      gadolinium-enhanced magnetic resonance imaging (MRI) to determine the frequency
      and distribution of CNS lesions. The associated clinical features were also
      reviewed. Thirty-six (72%) of the 50 had 1 or more CNS tumors. The most
      frequently affected sites in the CNS excluding the retina were the cerebellum
      (52%), spinal cord (44%), and brainstem (18%). New regional predilections for the
      craniocervical junction and conus medullaris were demonstrated by this study.
      Forty-one percent of all VHL patients with CNS tumors were neurologically
      asymptomatic: cerebellar tumors (50%), spinal cord tumors (50%), and brainstem
      tumors (44%) were often without clinical signs or symptoms. Multiple lesions were
      common. The mean age of all VHL patients (34.5 years) was similar to the mean age
      of all CNS VHL patients (34.4 years), suggesting a lack of age association. CNS
      lesions commonly occurred in the 2nd decade of life. All patients at risk for VHL
      should be evaluated using gadolinium-enhanced MRI after 10 years of age, although
      ophthalmic examination should be initiated within the 1st 2 years of life.
      Enhanced MRI is particularly useful in the detection of CNS tumors in patients
      with the VHL gene.

PMID- 1985295
TI  - Comparison of myelography with CT follow-up versus gadolinium MRI for
      subarachnoid metastatic disease in children.
AB  - We evaluated 17 children with primary intracranial neoplasms for subarachnoid
      metastatic disease (SAMD) using myelography with computed tomographic follow-up
      (Myelo + CT) and cerebrospinal fluid (CSF) histopathologic examination, as well
      as magnetic resonance imaging with gadolinium DTPA (MRI + Gd), between December
      1988 and December 1989. There were 12 boys, and the median age was 5.7 years
      (range, 0.8 to 21.8 years). Tumor histology included 8 primitive neuroectodermal
      tumors (PNETs), 3 ependymomas, 2 low-grade astrocytomas, 1 anaplastic
      astrocytoma, 1 glioblastoma multiforme, 1 atypical rhabdoid tumor, and 1
      malignant fibrous histiocytoma. Thirteen tumors originated in the posterior
      fossa, 2 were supratentorial, and 2 were in the spinal cord. The median interval
      between the 2 diagnostic tests was 2 days. MRI + Gd was positive in 11 (65%),
      Myelo + CT in 8 (47%), and CSF in 5 (29%) cases. MRI + Gd was superior in
      delineating spinal cord nodules and "sugar coating" whereas Myelo + CT more
      readily revealed nerve root sleeve filling defects. There was no case in which
      Myelo + CT was positive that MRI + Gd did not reveal SAMD. MRI + Gd is a safe,
      noninvasive test that should be used as the initial imaging modality for the
      presence of SAMD.

PMID- 1985296
TI  - Quantification of magnetic resonance scans for hippocampal and parahippocampal
      atrophy in Alzheimer's disease.
AB  - The brains of patients with Alzheimer's disease (AD) invariably exhibit
      neuropathology in the hippocampus and entorhinal cortex when examined postmortem.
      Magnetic resonance imaging (MRI) offers a noninvasive, high-resolution method for
      quantifying volumetric changes in the AD brain antemortem. Eight patients
      diagnosed with probable AD and 7 age-matched controls had MRI scans and were
      tested on a battery of cognitive and olfactory tests. The hippocampus and
      entorhinal cortex (parahippocampal gyrus) showed significant atrophy, with over
      40% reduction in size. Areas of the brain that are not highly involved in the
      degenerative state of AD, such as the striatum, did not show significant
      volumetric changes. Hippocampal and parahippocampal gyrus volumes had the highest
      correlation with scores on the Mini-Mental State Examination (r = 0.89), with
      lower correlations for a smell identification test (r = 0.65), odor match-to
      sample test (r = 0.72), and a visual match-to-sample test (r = 0.26).

PMID- 1985297
TI  - Early-onset Alzheimer's disease in 2 large Belgian families.
AB  - Familial Alzheimer's disease (FAD) is a dominantly inherited condition that may
      present with an early onset, and myoclonus occurs frequently in the course of the
      disease. We report clinical and neuropathologic data on 2 large Belgian families
      with FAD in which we obtained 17 autopsies of the CNS. In family A, each of 11
      autopsies had the typical neuropathologic features of Alzheimer's disease (AD),
      and there were a few cerebellar plaques in the molecular layer. In family B, in
      addition to the typical characteristics of AD in 6 autopsies, there were numerous
      amyloid plaques in the cortical cerebellar layers. In both families, we
      immunostained the amyloid deposits for the A4 protein, and they were negative for
      prion-associated protein immunoreactivity.

PMID- 1985298
TI  - Magnetic stimulation of the motor cortex in cervical spondylosis.
AB  - We report a new technique of transcranial magnetic stimulation of the motor
      cortex to measure conduction within central motor pathways of 67 patients with
      cervical spondylosis or disk herniation. There were upper motor neuron signs in
      34 patients (51%) and x-ray evidence of cervical cord compression in 44 (66%).
      Muscle action potentials (MAPs) to cortical stimulation were abnormal in 84% of
      patients with, and 22% of those without, radiologic signs of cervical cord
      compression. Median nerve somatosensory evoked potentials were altered in only
      25% of patients. The frequency of MAP alterations correlated with upper motor
      neuron signs. In 5 (11%) of the 44 patients with x-ray evidence of cervical cord
      compression, subclinical cord compression was disclosed by cortical stimulation.
      In 10 patients restudied 3 months after surgical decompression, normalization of
      central motor conduction time did not occur, indicating permanent damage to the
      cervical cord.

PMID- 1985299
TI  - Genetic linkage with chromosome 19 but not chromosome 17 in a family with
      myotonic dystrophy associated with hereditary motor and sensory neuropathy.
AB  - We identified a large kindred that shows classical myotonic dystrophy (MyD),
      together with hereditary motor and sensory neuropathy (HMSN) in some individuals,
      and HMSN alone in others. A previous study of this family has shown cosegregation
      of the MyD and HMSN phenotypes with the Lutheran and secretor loci in some
      branches of the family, indicating linkage to chromosome 19. We reanalyzed this
      family with 2 recombinant DNA marker systems from the ApoC2 locus on chromosome
      19. Our results demonstrate that all affected individuals have inherited a unique
      ApoC2 haplotype that was not found in their clinically and electrophysiologically
      normal sibs. We also obtained evidence against involvement of the HMSN I locus on
      chromosome 17. In this family, a moderately severe neuropathy may be the only
      clinical sign of MyD for many years. Our results are consistent with an unusual
      neuropathic mutation at the MyD gene. However, involvement of 2 closely linked
      genes (1 for MyD and the other for HMSN) can also explain our findings.

PMID- 1985300
TI  - Tropical spastic paraparesis-like illness occurring in a patient dually infected
      with HIV-1 and HTLV-II.
AB  - We describe a 34-year-old man from southern Florida with a history of intravenous
      drug use, dually infected with human immunodeficiency virus type 1 (HIV-1) and
      human T-lymphotropic virus type II (HTLV-II), who developed a myelopathy
      clinically indistinguishable from HTLV-I-associated myelopathy/tropical spastic
      paraparesis (HAM/TSP). This myelopathy was characterized by spastic lower
      extremity weakness, distal paresthesias, sensory loss with a discrete thoracic
      level to pinprick, back pain, impotence, and sphincter disturbances. Nerve
      conduction studies revealed an associated mixed axonal and demyelinative
      neuropathy. Despite a lack of response to 10 months of zidovudine therapy, the
      myeloneuropathy improved dramatically 2 years after its onset in the absence of
      any therapeutic intervention.

PMID- 1985301
TI  - Combined therapy with MK-801 and nimodipine for protection of ischemic brain
      damage.
AB  - Calcium ion can enter ischemic neurons through both receptor-operated and voltage
      sensitive Ca2+ channels. To attenuate this Ca2+ entry and Ca2(+)-induced neuronal
      injury, we tried a combined treatment with the noncompetitive N-methyl-D
      aspartate (NMDA) antagonist, MK-801, and the dihydropyridine calcium antagonist,
      nimodipine, in a cat middle cerebral artery occlusion (1 hour) and reperfusion (3
      hours) model. We measured changes in cytosolic free calcium, nicotinamide adenine
      dinucleotide/reduced nicotinamide adenine dinucleotide redox state, and blood
      flow in the cat cortex using a newly developed fluorometric technique with indo
      1, a fluorescent intracellular Ca2+ indicator. The combined treatment, starting 5
      minutes into ischemia, was effective in reducing both Ca2+ entry and histologic
      damage and in enhancing recovery of the electroencephalogram following
      reperfusion. MK-801 alone was also effective, but to a lesser extent. These data
      suggest that the dual blockade of Ca2+ entry using MK-801 and nimodipine may be a
      useful tool for protection against ischemic brain damage.

PMID- 1985303
TI  - Fluoroquinolones. New miracle drugs?
AB  - Fluoroquinolones are the newest antibiotics for treatment of some infections
      caused by highly resistant bacteria (eg, Pseudomonas aeruginosa). Clinically
      sound indications for these drugs include resistant infections of the urinary,
      intestinal, and respiratory tracts; otitis externa; osteomyelitis; foot
      infections in diabetic patients; and late infections complicating burns.
      Fluoroquinolone therapy is not indicated in children younger than 12 years old
      and patients with foreign bodies, abscesses, pelvic inflammatory disease, or
      infections requiring a prophylactic antibiotic. Drug interactions with antacids
      or theophylline may occur.

PMID- 1985302
TI  - Primary leptomeningeal lymphoma: report of 9 cases, diagnosis with
      immunocytochemical analysis, and review of the literature.
AB  - We describe 9 patients who presented with a neoplastic meningitis of lymphomatous
      origin. No evidence of parenchymal central nervous system or systemic tumor was
      identified either at the time of presentation or throughout the course of their
      disease. We have chosen to call this entity "primary leptomeningeal lymphoma"
      (PLML). This unusual form of neurologic lymphoma must be differentiated from the
      more common clinical situations of primary parenchymal lymphoma with meningeal
      involvement and systemic lymphoma complicated by lymphomatous meningitis.

PMID- 1985304
TI  - Resuscitation. Revival should be the first priority.
AB  - During resuscitation, it is important to distinguish between those maneuvers
      directed at patient revival and those directed at examination and measurement.
      Revival should always be the top priority. The steps for revival are easily
      remembered as ABCDEF: Airway, Breathing, Circulation, Decompression, Elimination,
      and Fluids. Once these steps have been completed, vital functions can be assessed
      and measurements to aid in diagnosis can be taken.

PMID- 1985305
TI  - Asthma and pregnancy. A challenge for everyone concerned.
AB  - The asthmatic patient who becomes pregnant needs expert management to minimize
      the possibility of a poor outcome. Dr Barsky stresses the importance of good
      rapport and cooperation between physician and patient, explains the effects of
      pregnancy on asthma and vice versa, and discusses the pharmacotherapy that is
      often necessary to maintain the health of both mother and baby.

PMID- 1985306
TI  - Preventing falls in your elderly patients.
AB  - An elderly patient who falls is at significant risk for disability or death. In
      this article, Dr Costa explains how a carefully taken history, detailed physical
      examination, and appropriate laboratory studies can help to discern the cause of
      a fall. He also describes a multifaceted approach to preventing falls in elderly
      patients that involves a partnership of the physician, the patient, and the
      family.

PMID- 1985307
TI  - Hemorrhoids. A practical approach to an aggravating problem.
AB  - Although hemorrhoids are considered a minor medical problem, they may cause
      considerable discomfort and anxiety. Fortunately, treatment is often simple and
      surgery is rarely necessary. In this practical article, Dr Cocchiara describes
      internal and external hemorrhoids, a classification system, and treatment choices
      based on the degree of involvement.

PMID- 1985308
TI  - 'HCFA police,' lab tests, prison, and you!

PMID- 1985309
TI  - The link between stress and illness. Do our coping methods influence our health?
AB  - Stress is an important fact of everyday life that can have a major effect on
      emotional and physical well-being. Stress is best defined as the adaptation
      response by the body to a stressor (ie, the perceived stimulus).
      Psychoneuroimmunology is the study of the ways in which psychosocial interactions
      cause neuroendocrine responses and, at times, physical changes. An increasing
      body of evidence suggests a causative role for acute and chronic stress in many
      medical disorders and psychiatric states. Methods of measuring and assessing
      stress factors need to also evaluate patients' coping and adaptive mechanisms.

PMID- 1985310
TI  - Weaning patients from mechanical ventilation. How to avoid difficulty.
AB  - The majority of patients can be easily weaned from mechanical ventilation, but a
      substantial minority pose considerable difficulty. In such cases, the cause of
      ventilator dependency should be identified and correctable factors should be
      rectified. An organized plan of management, a team approach, optimal pulmonary
      and general patient care, and nutritional supplementation are important factors
      in successful weaning.

PMID- 1985311
TI  - Agranulocytosis from antiarrhythmic agents. What to watch for when a medication
      is first prescribed.
AB  - Anyone who prescribes antiarrhythmic medications should strongly consider
      monitoring patients for the first 3 months of its use. If agranulocytosis is
      going to develop, it almost always does so in that period. A complete blood cell
      count every 1 to 2 weeks can detect neutropenia before symptoms and infectious
      complications appear. Fever and associated systemic symptoms should always induce
      evaluation. Treatment involves discontinuation of the causative agent, use of
      antibiotics and antifungal drugs for infectious complications as needed, and
      close observation. Spontaneous recovery should occur within 5 weeks. If it does
      not, a nonpharmacologic cause should be considered.

PMID- 1985312
TI  - Syphilis. A new visit from an old enemy.
AB  - Syphilis has a number of stages, including a latent one, and may be overlooked or
      misdiagnosed if the possibility is not kept in mind. Adequate treatment during
      the primary stage results in a very high cure rate. The latent stage may last for
      years, during which time a woman may still give birth to an infected child.
      Symptomatic neurosyphilis occurs more often in men than women. Penicillin G is
      preferred to treat all stages of the disease; other antibiotics can be used for
      patients sensitive to penicillin.

PMID- 1985313
TI  - Managing abnormal vaginal bleeding.
AB  - Abnormal vaginal bleeding is a diagnostic and therapeutic challenge. A carefully
      directed patient history and physical examination along with basic laboratory
      tests can lead to accurate diagnosis. In most cases, symptoms can be controlled
      with use of oral contraceptives, progesterone supplements, and/or nonsteroidal
      anti-inflammatory drugs.

PMID- 1985314
TI  - Hyperbaric oxygen therapy for acute smoke inhalation injuries.
AB  - Hyperbaric oxygen therapy is an important adjunct in the management of
      respiratory injuries secondary to smoke inhalation, especially when injury is
      complicated by inhalation of a toxic chemical such as carbon monoxide or cyanide.
      For carbon monoxide poisoning, such therapy has become a standard of practice. As
      more information becomes available concerning the ability of hyperbaric oxygen to
      reduce reperfusion injuries, we anticipate that this therapy will become a
      standard of practice for managing smoke inhalation injuries and cyanide poisoning
      as well.

PMID- 1985315
TI  - Would you recognize celiac axis syndrome?
AB  - Since its original description, celiac axis syndrome has been a topic of debate.
      Clinical findings include postprandial abdominal pain, weight loss, and an
      epigastric bruit. Diagnosis is often made by exclusion and is confirmed by
      lateral aortography. The role of surgery in treating celiac axis syndrome is
      controversial.

PMID- 1985316
TI  - Spontaneous pneumomediastinum. An unusual cause of a sore throat.
AB  - Sore throat, usually related to pharyngitis, is a common presenting symptom in
      the primary care setting. Drs Frenkel and Lyons describe a case showing that
      physicians need to be aware of another, puzzling cause--spontaneous pneumo
      mediastinum.

PMID- 1985317
TI  - Pap tests needed for women of all ages.

PMID- 1985318
TI  - Living wills and the law.

PMID- 1985319
TI  - Assessment of stable ischemic heart disease. Which tests are best for which
      patients?
AB  - An understanding of the importance of various risk factors, the pathogenesis of
      myocardial ischemia, and the appropriate use of various noninvasive and invasive
      tests is essential for management of patients with known or suspected coronary
      artery disease (CAD). Although coronary angiography remains the "gold standard"
      for diagnosis of CAD, much of the data obtained from risk factor assessment,
      medical history, and various noninvasive tests provides information that may be
      even more important than cardiac catheterization data alone for defining
      prognosis and directing management.

PMID- 1985321
TI  - Metabolic bone disease.

PMID- 1985320
TI  - Treating serum lipid abnormalities in high-priority patients.
AB  - Normalization of serum lipid levels should be initiated as soon as possible in
      patients with myocardial, cerebrovascular, or peripheral vascular disease.
      Clinical trials indicate that coronary artery disease and overall mortality rates
      can be reduced and atherosclerosis stabilized or reversed by lipid-lowering
      therapy. Treatment should lower low-density lipoprotein cholesterol levels to 130
      mg/dL or less and total triglyceride levels to 150 mg/dL or less and increase
      high-density lipoprotein cholesterol levels to at least 52 mg/dL in men and 66
      mg/dL in women. Nonlipid coronary risk factors should be eliminated when
      possible. Lipid-lowering therapy may consist of dietary modification and drug
      treatment with colestipol hydrochloride (Colestid), cholestyramine (Cholybar,
      Questran), lovastatin (Mevacor), gemfibrozil (Lopid), and nicotinic acid
      (Nicolar).

PMID- 1985322
TI  - Biomechanics of fracture risk prediction of the hip and spine by quantitative
      computed tomography.
AB  - In this review, we have made use of some simple engineering concepts to summarize
      current efforts relating QCT measures to bone density and strength. From a
      variety of in vitro experiments on cadaveric vertebrae and femora, it is evident
      that both apparent and ash densities are strong linear functions of QCT measures,
      with coefficients of determination ranging from 0.49 to 0.90 and relative errors
      from 44.9% to 7.1%. QCT data also can be used (with somewhat less confidence) to
      determine the compressive modulus (R2s from 0.36 to 0.68, relative errors from
      45.0% to 35.5%) and compressive strength (R2s from 0.58 to 0.70, relative errors
      from 56.5% to 39.9%) of trabecular bone from the proximal femur and vertebral
      body. In cortical bone, material properties are only correlated weakly with QCT
      measures. Experiments designed to relate QCT data to failure loads for the
      proximal femur and vertebral body have been remarkably successful. Coefficients
      of determination have ranged from 0.32 to 0.93, with relative errors from 31.1%
      to 13.9%. However, when the in vitro failure loads determined in these
      experiments are compared against available estimates of in vivo loads on the
      spine and hip, it is apparent, at least in the elderly, that in vivo loads are
      relatively close to those that cause fracture in vitro. To assess the possibility
      of developing QCT-based clinical predictors of fracture risk for individual
      patients, we have introduced the concept factor of risk often used in engineering
      design to account for uncertainties in estimates of service loads and component
      strength. The factor of risk for a particular loading condition is defined as the
      ratio of expected service loads to the known failure loads. To extend this
      concept to densitometric fracture risk prediction in vivo, it is important to
      recognize that densitometric data must not only be used to predict the ultimate
      load carrying capacity of the region of interest, but that this ultimate load
      must then be compared to the forces expected in vivo under comparable loading
      conditions. One difficulty with this approach is that little is known about the
      in vivo forces that are associated with atraumatic age-related fractures of the
      hip and vertebrae and even less about the forces applied to the hip and spine
      during traumatic events such as falls. However, from available estimates of in
      vivo loads during bending and lifting, it is apparent that in the elderly,
      factors of risk for the spine can easily approach 1.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 1985323
TI  - Skeletal manifestations of ectopic or inappropriate endocrine and metabolic
      syndromes.
AB  - A variety of tumors and nontumorous lesions were used to illustrate some of the
      biologic, clinical, and pathologic aspects of inappropriate or ectopic endocrine
      and metabolic syndromes that have musculoskeletal repercussions. It is clear,
      both from the discussion and case material, that many mechanisms of ectopic
      endocrine syndromes have yet to be clarified. Elaborate techniques are available
      for hormonal estimations, but their routine use is prohibitively expensive and
      relatively unrewarding. Cells of a given lesion may be functionally heterogeneous
      or may fail to elaborate active products in substantial amounts. Different cells
      may produce similar peptides, while the same cells can produce more than one.
      Despite these difficulties, recognition of ectopic endocrine syndromes remains
      crucial to diagnosis and patient management, and thus corroboration or
      correlation must often rest on a cruder basis. In fact, the clinical significance
      of basic laboratory data, e.g., PTH elevation, may vary, as PTH may be
      immunoreactive but biologically inactive. As another example, hypercalcemia
      associated with myeloma may be variously related to coexistent
      hyperparathyroidism, renal disease, dehydration, or humoral osteolysis.
      Therefore, roentgenographic evidence of bone destruction or skeletal stigmata of
      hyperparathyroidism imbues laboratory data with greater significance.
      Paraneoplastic syndromes are of particular concern to the radiologist, as
      multiple systemic manifestations, occurring either synchronously or
      metachronously, may suggest the presence of an underlying or unifying lesion or
      even of a specific type of neoplasm. They may precede detection of neoplasms by
      months to years and can develop at any time during their course. Paraneoplastic
      syndromes may, furthermore, parallel the course of a lesion and be used as
      indicators of remission or recurrence. Conversely, those unassociated with overt
      symptoms possess endocrine markers that can reinforce sometimes silent skeletal
      stigmata. Familiarity with representative secretory products influencing the
      musculoskeletal system per se may often clarify seemingly innocuous and sometimes
      asymptomatic skeletal findings. Alert imagers may, therefore, detect, infer, or
      suspect particular syndromes when they present in a specific sequence or mosaic.
      Conversely, when apprised of their existence, imagers should know where their
      related effects may be sought or anticipated. Such relationships, sometimes
      serendipitously discovered, may be valuable assets in clinical diagnosis and
      patient management in both suspected and unsuspected cases.

PMID- 1985324
TI  - Radiologic manifestations in the musculoskeletal system of miscellaneous
      endocrine disorders.
AB  - The manifestations of endocrine derangements in the musculoskeletal system in
      infancy and childhood are disturbances in growth and maturation and in adulthood
      are disturbances in maintenance and metabolism. Hypercortisolism during skeletal
      immaturity suppresses growth. In the adult, hypercortisolism leads to
      osteoporosis, osteonecrosis, and muscle wasting. Deficiency of growth hormone
      during skeletal development results in short stature. An excess of growth hormone
      in a skeletally immature individual results in gigantism, an excess in a
      skeletally mature individual results in acromegaly. Patients with gigantism have
      extreme height with normal body proportions. Musculoskeletal manifestations of
      acromegaly include soft-tissue thickening, vertebral body enlargement,
      characteristic hand and foot changes, and enthesal bony proliferation.
      Hyperthyroidism causes catabolism of protein and loss of connective tissue, which
      manifest as muscle wasting. Deficient levels of thyroid hormone cause defects in
      growth and development. Severe growth retardation from congenital hypothyroidism
      is rare because neonatal screening recognizes the disorder and leads to early
      treatment. The skeletal manifestation of hypergonadism in children is precocious
      growth and early skeletal maturation. Although the initial precocious growth
      spurt results in a tall child, early closure of the growth plates results in a
      short adult. Hypogonadism in the prepubertal child results in delayed adolescence
      and delayed skeletal maturation. Diabetes mellitus in childhood results in
      decreased growth, a phenomenon presumed to be secondary to nutritional
      abnormalities. Generalized osteoporosis and short stature are common. In the
      adult, generalized osteoporosis may accompany insulin-dependent diabetes mellitus
      if obesity is absent. Calcification of interdigital arteries of the foot is
      common in diabetics and uncommon in other conditions. Additional skeletal
      manifestations relate to complications of diabetes such as peripheral neuropathy
      and diabetic foot disease.

PMID- 1985325
TI  - Inherited diseases of bone density in children.
AB  - In this article the radiographic manifestations of various genetic diseases
      predominately affecting bone mineralization are considered. Osteogenesis
      imperfecta and other diseases of diffuse osteopenia, hereditary rickets and
      rachiticlike conditions, and osteopetrosis and other diseases of increased bone
      density are emphasized. Recognition of the radiographic manifestations allows
      accurate diagnosis, therapeutic intervention when possible, and determination of
      recurrence risk for genetic counseling.

PMID- 1985326
TI  - Metabolic bone disease. Morphometry.
AB  - The history of the development of radiologic morphometric techniques is traced,
      emphasizing their pathophysiologic background and relevance to possible
      therapies. The techniques are described and longitudinal and comparative studies
      assessed. Technical limitations of the various methods are presented.

PMID- 1985327
TI  - The pathology of metabolic bone disease.
AB  - The skeletal manifestations of the diverse group of metabolic bone diseases are
      mediated through the altered function of osteoblasts and osteoclasts and abnormal
      rates of mineralization. Appropriate understanding of their pathologic conditions
      requires familiarity with the normal anatomy and physiology of the skeleton. The
      accurate identification of metabolic bone disease frequently demands histologic
      confirmation and sophisticated analysis of undecalcified bone specimens labeled
      with tetracycline by histomorphometric techniques. These procedures allow the
      assessment of many morphologic features that characterize specific disease
      states. The most common types of metabolic bone diseases are acquired disorders;
      nonetheless, rare forms frequently are genetically based and cause intrinsic
      alterations in the bone-cell populations.

PMID- 1985328
TI  - Radiographic appearance of osteopenia.
AB  - The radiographic appearance of bone is the result of two physiologic processes:
      the resorption of bone and the remodeling of bone in response to the stresses
      applied to it. The relative rates of these two processes will determine the
      structural and, therefore, the radiographic appearance of the affected bone.

PMID- 1985329
TI  - Osteoporosis. Current techniques and recent developments in quantitative bone
      densitometry.
AB  - Knowledge about the proper use and interpretation of bone densitometry studies
      and an understanding of appropriate medical interventions are not universal among
      physicians, nor are instrumentation and technical performance of bone density
      studies of uniformly high quality. Indeed, this deficiency of medical and
      technical expertise is the principal deterrent to widespread implementation of
      our recommended clinical applications at this time. Nonetheless, given the
      current impetus to disseminate information about osteoporosis, to make newer
      instrumentation more readily available, and to limit the cost of these
      techniques, we anticipate that our recommendations may soon become standard
      medical practice.

PMID- 1985330
TI  - Osteoporosis.
AB  - Osteoporosis, a condition of decreased bone tissue that increases the likelihood
      of fracture, places a significant burden on our society in terms of health cost
      and morbidity. The most common type of osteoporosis is involutional, and two
      subtypes are recognized: type 1 and type 2. Type 1, or postmenopausal,
      osteoporosis is most commonly seen in perimenopausal and postmenopausal women
      from ages 51 to 75. Estrogen deficiency is the most dominant factor in the
      pathogenesis of this disorder. Type 2, or aging related, osteoporosis is seen in
      elderly women and men aged 70 or more. Bone loss in this group is related to
      aging, estrogen deficiency, negative calcium balance, and a variety of
      environmental and genetic factors. The best approach to the management of
      osteoporosis is to develop a lifelong strategy that maximizes peak bone mass and
      minimizes aging-related and postmenopausal bone loss. Estrogen is the only
      medication approved for the prevention of bone loss that is in general use. Other
      strategies to prevent bone loss (and maximize peak bone mass) include adequate
      calcium intake, adequate exercise, and avoidance of excess alcohol, tobacco, and
      caffeine use.

PMID- 1985331
TI  - Hyperparathyroidism.
AB  - Since the introduction of routine automated measurements of serum calcium levels
      in the 1970s, the detection of primary hyperparathyroidism has risen
      considerably. Nevertheless, the severe bone changes described by von
      Recklinghausen are still quite rare. The apparent rise in incidence is accounted
      for by the discovery of a large group of predominantly asymptomatic elderly
      patients who have mild primary hyperparathyroidism. Because the diagnosis is most
      often confirmed through laboratory tests, radiologic studies are now most useful
      in assessing the severity of the disease. The presence of bone changes is an
      accepted indication for parathyroid surgery in primary hyperparathyroidism. For
      patients with asymptomatic disease in whom nonsurgical treatment may be
      considered, radiographic evaluation is one of several techniques that may be used
      to assess progression. High resolution radiographs of the hands are most valuable
      in this regard. Accelerated bone mineral loss, as measured by quantitative
      techniques, will probably play a significant role in the future. Radiographic
      follow-up of patients with renal disease and secondary hyperparathyroidism is
      equally important, as increased bone or soft tissue changes may indicate a need
      for therapeutic change. Radiographically identifiable changes of
      hyperparathyroidism consist mainly of various types of accelerated bone
      resorption. Multifocal subperiosteal resorption is generally considered to be
      pathognomonic of hyperparathyroidism. Subligamentous, subchondral, endosteal, and
      intracortical resorption are also important manifestations of accelerated bone
      turnover. The earliest bone changes are visible in the hands and should be
      searched for especially carefully in the phalanges and terminal tufts. Only
      occasionally will changes be found elsewhere in the skeleton when hand changes
      are not present.

PMID- 1985332
TI  - Rickets and osteomalacia are still around.
AB  - The terms rickets and osteomalacia describe gross, histologic, and radiologic
      abnormalities common to more than 50 diseases that vary in cause and clinical
      presentation. Rachitic and osteomalacic syndromes seen in current clinical
      practice usually are resistant to vitamin D forms and are most often caused by
      phosphate loss or 1,25(OH)2D deficiency, or both. Radiographic identification of
      rachitic or osteomalacic syndromes and accurate diagnosis of a particular cause
      is essential, as many patients' conditions can be improved or cured with proper
      therapy.

PMID- 1985333
TI  - Adenocarcinoma of the colon and rectum in patients less than 40 years of age.
AB  - From 1962 to 1988, 50 of 801 patients with adenocarcinoma of the colon and rectum
      treated at the National Naval Medical Center were less than 40 years old.
      Symptoms were present in 47 of the younger patients at presentation. The mean
      duration of time from the onset of symptoms to diagnosis in this group was 4.9
      months. Risk factors for carcinoma of the colon and rectum were identified in 14
      of 50 patients less than 40 years old. A significantly greater proportion of
      patients less than 40 years old had Stage C disease compared with the older group
      of patients (42 versus 22 per cent, p = 0.014). Stage B disease was more common
      in patients more than 40 years of age (44.8 versus 26.0 per cent, p = 0.014). The
      proportion of patients with Stages A and D disease was similar in both age
      groups. The cumulative survival rate in this group at five and ten years was 43
      and 34 per cent, respectively. The five year survival rate in patients less than
      40 years old with Stage B disease was 76 per cent and with Stage C disease, 37
      per cent. All young patients with Stage D disease were dead at 28 months.
      Synchronous and metachronous carcinomas of the colon and rectum were uncommon in
      patients less than 40 years old. Patients less than 40 years of age with
      carcinoma of the colon and rectum are usually symptomatic and have advanced
      disease at the time of presentation. Survival time for these patients for each
      stage of disease is similar to the over-all population of patients with carcinoma
      of the colon and rectum.

PMID- 1985334
TI  - Prevalence of hemodynamically significant stenosis of the carotid artery in an
      asymptomatic veteran population.
AB  - The results of previous studies have suggested that significant stenosis of the
      carotid artery occurs in less than 6 per cent of asymptomatic patients. However,
      some populations studied were not representative of those seen by most vascular
      surgeons. Accordingly, we examined two cohorts of patients at the Veterans
      Administration Medical Center using Duplex scanning. There were 153 volunteers in
      group 1, all more than 50 years of age, who were being treated at our outpatient
      department for nonvascular problems. There were 116 patients of similar age in
      group 2 but who were known to have significant arterial occlusive disease of the
      lower extremity. The majority of patients were men with a mean age of 64.4 years.
      Risk factors in the total population included hypertension, diabetes mellitus,
      coronary arterial disease, peripheral vascular disease and smoking. Over-all,
      significant (greater than 50 per cent diameter) stenosis of the carotid artery
      was discovered in 25 of 269 patients. The prevalence for those in group 1 was 6.5
      per cent versus 12.9 per cent for those in group 2 (p = 0.058). The prevalence in
      patients with cardiac disease was 15.2 per cent compared with 6.8 per cent in
      those without cardiac disease (p = 0.032). Smoking was associated with a 10.6 per
      cent rate of significant disease compared with a 2.3 per cent rate in nonsmokers
      (p = 0.065). Hypertension and diabetes were not significant risk factors.
      Significant stenosis of the carotid artery was found in seven of 40 patients in
      whom coronary arterial disease, peripheral vascular disease and smoking were all
      present.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1985335
TI  - The oncologic risks of skin preservation at mastectomy when combined with
      immediate reconstruction of the breast.
AB  - Most oncologic surgeons agree that removal of the nipple, the areola and any
      recent scar at the site of the biopsy is necessary during a mastectomy for
      treatment of carcinoma of the breast. There is less agreement about what should
      be done with the remaining uninvolved mammary skin. Its preservation facilitates
      the performance of immediate reconstruction of the breast and can lead to
      improved aesthetic results, but many oncologists fear that this practice could
      lead to an increased incidence of local tumor recurrence. To determine if that
      fear was justified, 87 patients who had undergone unilateral or bilateral
      mastectomy with immediate reconstruction for treatment of early carcinoma of the
      breast were studied. Preservation of uninvolved skin was used in all instances.
      All patients had a documented follow-up study of 12 months or more; the average
      follow-up time was 23.1 months. One peripheral local recurrence was observed.
      This 1.2 per cent rate of early local recurrence is lower than that reported from
      several series using modified radical mastectomy without skin preservation or
      immediate reconstruction, and suggests that skin preservation does not confer
      additional risks of local recurrence of carcinoma of the breast in properly
      selected patients.

PMID- 1985336
TI  - Cholecystokinin enhanced hepatobiliary scanning with ejection fraction
      calculation as an indicator of disease of the gallbladder.
AB  - Chronic acalculous cholecystitis represents 5 to 20 per cent of electively
      treated diseases of the gallbladder. A 70 per cent success rate in relieving
      these patients of chronic pain was reported when surgical treatment was
      recommended based on symptoms alone. The cholecystokinin ejection fraction, which
      is a quantitative measure of emptying of the gallbladder, was 95 per cent
      accurate in predicting which patients would be relieved of symptoms by surgical
      treatment. In this study, we report our consecutive experience during a 20 month
      period with 83 patients.

PMID- 1985337
TI  - The natural history of renal stone disease after parathyroidectomy for primary
      hyperparathyroidism.
AB  - The evolution of renal stone disease has been followed, before and after
      parathyroidectomy, in 197 patients with primary hyperparathyroidism. Before
      operation, 120 patients had had a previous history of renal colics or stones, or
      both, demonstrated on roentgenograms of the urinary tract. In 36 patients with
      stones that had been passed or removed before exploration of the neck, no
      recurrence of lithiasis has been observed. In 84 patients who still had stones at
      the time of the operation, the stones dissolved and disappeared within ten years
      in 88 per cent of those with urolithiasis and in 77 per cent with
      nephrocalcinosis. The rate of stone disappearance was similar in those with or
      without preoperative urinary tract infection and in patients operated upon for
      adenoma of the parathyroid gland or primary hyperplasia. This rate was slower for
      patients with a postoperative urinary infection. The frequency of renal colics,
      0.66 per patient per year before parathyroidectomy, decreased to 0.02 per patient
      per year after the first postoperative year.

PMID- 1985338
TI  - Prognostic significance of serosal invasion in carcinoma of the stomach.
AB  - Two hundred and seventy-seven patients with advanced carcinoma of the stomach
      invading the serosa were studied with regard to the relationship between the
      length of the serosal invasion (LSI) and prognosis, with a division made between
      expanding and infiltrative types of tumors. Among patients with expanding types
      of tumors, five year survival rates were 40 per cent in patients with LSI less
      than 4.0 centimeters, 33 per cent in patients with LSI 4.1 to 6.0 centimeters and
      13.0 per cent in patients with LSI more than 6.0 centimeters. Among those
      patients with infiltrative types of tumors, those with less than 2.0 centimeters
      of LSI had a better prognosis (five year survival rate of 53 per cent), whereas
      those patients with a LSI more than 2.0 centimeters had a very poor prognosis
      (five year survival rate of less than 20 per cent) and the significant LSI on
      prognosis was found to be 2.0 centimeters. Involvement of the lymph node and
      metastasis to the liver were not affected by LSI, whereas the rates of peritoneal
      dissemination and direct invasion to neighboring organs increased with an
      increase in LSI. Knowledge of these factors facilitates the planning of
      postoperative treatment.

PMID- 1985339
TI  - Gastric lymphoma.
AB  - From 1976 to 1988, 35 patients were treated for Stage IE and Stage IIE primary
      gastric lymphoma (non-Hodgkin's). Pain and weight loss were the predominant
      symptoms, physical findings were usually absent and 20 per cent of the patients
      were anemic. The results of gastrointestinal contrast studies suggested a
      malignant condition in 75 per cent, but findings were not specific for lymphoma.
      Endoscopic findings suggested a malignant process in 85 per cent, but the yield
      for biopsy was only 60 per cent. Of 28 patients undergoing operative exploration,
      75 per cent were resectable. Nine patients received postresectional adjuvant
      therapy. Five had chemotherapy; three, radiotherapy, and one patient, a
      combination of the two. Primary nonsurgical treatment consisted of chemotherapy
      in 11, radiotherapy in two and combined therapy in one instance. Three of five
      recurrences were successfully treated. The five year survival rate was 65 per
      cent without significant differences between surgical and nonsurgical regimens.
      Those with tumors smaller than 7 centimeters had a five year survival rate of 100
      per cent versus 50 per cent for larger neoplasms. Patients more than 60 years of
      age appeared to have a more favorable course after surgical therapy compared with
      those who had nonsurgical treatment. We concluded that endoscopy is a most
      useful, although limited diagnostic study and since no treatment program is
      obviously superior, the choice of therapy can be individualized accordingly.

PMID- 1985340
TI  - Isoperistaltic intestinal lengthening for short bowel syndrome.
AB  - Because of improvements in supportive care, many infants now survive massive
      intestinal loss and have short bowel syndrome. Unfortunately, some survivors are
      left with an insufficient amount of intestine and cannot be weaned from total
      parenteral nutrition. An isoperistaltic intestinal lengthening procedure was used
      to treat surgically two such infants with 25 centimeters of remaining small
      intestine and absent ileocecal valves. This surgical technique longitudinally
      divides the short, dilated small intestine into two smaller, parallel lumens that
      are anastomosed end to end. This procedure preserves all mucosa, prolongs transit
      time by doubling intestinal length and corrects the ineffective peristalsis by
      tapering the dilated intestine. The lengthening technique can be performed
      because of the anatomic division of the intestinal vasculature within two leaves
      of the mesentery. Longitudinal division between the two leaves maintains
      vasculature to each side of the intestine. The isoperistaltic intestinal
      lengthening procedure, as it was successfully applied to two infants, is
      described in detail.

PMID- 1985341
TI  - An algorithm for diagnosis and therapy of management and complications of
      urolithiasis during pregnancy.
AB  - From 1 January 1986 to 30 June 1989, 15 pregnant women were diagnosed as having
      urolithiasis. Patients presented in the last two trimesters with an infection of
      the lower part of the urinary tract (60 per cent), flank and abdominal pain (27
      per cent) and hematuria (13 per cent). Ultrasonographic findings confirmed the
      diagnosis in 47 per cent of the patients. Other roentgenologic procedures were
      required in the remaining patients. Initially, therapy was conservative in all,
      and in 67 per cent of patients, no further intervention was necessary. Only 33
      per cent required invasive measures; cystoscopic passage of an internal ureteral
      stent was the initial procedure of choice at our institution. Three of five
      patients who underwent invasive procedures had surgical intervention for relief
      of ureteral obstruction. Intensive care management was necessary for one of these
      three patients who had acute hemorrhage occur during the procedure. These data
      emphasize the need for the accurate diagnosis of urolithiasis during pregnancy.
      Ultrasonography was a valuable diagnostic technique, but a limited excretory
      urogram is safe and appropriate when there is uncertainty. Conservative
      management (hydration, analgesia and antibiotics as indicated) of obstructive
      uropathy was successful in the majority of instances. A specific clinical
      algorithm facilitated the successful management of patients necessitating
      operative intervention. Optimal management requires clinical suspicion and a
      precise diagnostic and therapeutic plan.

PMID- 1985343
TI  - An even simpler method of skin closure by one surgeon.

PMID- 1985342
TI  - Effect of closing dead space on incidence of seroma after mastectomy.
AB  - Seromas are a significant cause of morbidity after modified radical mastectomy.
      The effect of closing dead space by suturing skin flaps to underlying muscle
      combined with early removal (48 hours postoperatively) of closed suction drains
      on formation of the seroma was evaluated prospectively in 37 patients. Thirty
      three underwent modified radical mastectomy for invasive carcinoma while four
      underwent total mastectomy with a level 1 axillary dissection for multifocal
      intraductal carcinoma. Seromas occurred in three, all were minor, two required
      one aspiration only and one required two aspirations. Two were seromas of the
      lower flap while one was an axillary seroma. Except for one patient who had a
      wound hematoma develop, no other instances of morbidity were noted. Closing dead
      space by suturing skin flaps to underlying muscle combined with early removal of
      closed suction drains is associated with a low incidence of seroma formation
      after mastectomy. Use of this technique has important economic and clinical
      implications for patients who had mastectomy.

PMID- 1985344
TI  - Snuffbox arteriovenous fistula.

PMID- 1985345
TI  - New position for easier access to the subdiaphragmatic region.

PMID- 1985346
TI  - A closed system for intraoperative cystic duct cholangiography.

PMID- 1985347
TI  - Technique for positioning the Sengstaken-Blakemore tube as comfortably as
      possible.

PMID- 1985348
TI  - Leonard Wood as the modern renaissance man.

PMID- 1985349
TI  - Neuroblastoma and the clinical significance of N-myc oncogene amplification.

PMID- 1985350
TI  - Strategies for trauma resuscitation.
AB  - Victims of penetrating trauma often arrive at a trauma center within minutes of
      sustaining their injury but nevertheless are in a state of deep circulatory
      shock. Such patients require extensive resuscitative efforts; in particular, some
      benefit from rapid, massive normothermic fluid resuscitation. During an initial
      one year period, 153 of 730 patients required immediate operation and, of these,
      33 required rapid infusion defined as greater than 5 liters per hour during the
      first hour. The over-all survival rate of those operated upon was 79 per cent.
      Encouraged by these data, the rapid infusor (Level 1 H-500) (Level 1,
      Technologies, Inc.) was modified to further increase normothermic fluid delivery
      to 500 milliliters per minute. Eleven of the subsequent 205 patients required
      rapid infusion. There was a statistically significant improvement in clinical
      flow rates, decrement in resuscitation times and unexpected survival. In
      particular, the latter group (nine survivors) included four who were clinically
      dead in the field or on arrival at the trauma center, or both. Rapid infusion of
      normothermic fluids may be of benefit not only in penetrating trauma but also
      more generally in the management of massive hemorrhage.

PMID- 1985351
TI  - The role of mammographic parenchymal patterns in screening for carcinoma of the
      breast.

PMID- 1985352
TI  - Angiographic contrast media interference with laser-induced fluorescence
      excitation and detection in atherosclerotic human coronary arteries.
AB  - Laser-induced fluorescence has been used in conjunction with angiography for
      laser angioplasty guidance. The effect of radiopaque contrast media on the
      excitation and detection of arterial fluorescence has not been previously
      reported. Accordingly, fluorescence emission spectra from human coronary artery
      necropsy specimens (n = 7) during excitation with pulsed excimer laser excitation
      (308 nm) was examined before and after the addition of three different contrast
      media, sodium and meglumine diatrizoate, sodium and meglumine ioxaglate, and
      iopamidol. A decrease in overall fluorescence intensity was observed at all
      wavelengths for each contrast agent examined. The decrease in intensity of
      fluorescence emission was more marked at wavelengths less than 410 nm than at
      wavelengths above 425 nm. Similar effects were observed for contrast media
      diluted with whole blood. Absorption spectra for all three contrast media
      demonstrated absorption in the ultraviolet centered around 240 nm. We conclude
      that preferential absorption in the ultraviolet range by contrast media
      interferes with the excitation and detection of laser-induced fluorescence; use
      of visible light excitation may obviate interference with laser-induced
      fluorescence analysis of plaque.

PMID- 1985354
TI  - Coronary angioplasty of diffuse coronary artery disease.
AB  - From January 1983 through December 1987, 98 patients underwent angioplasty of at
      least one diffusely diseased coronary artery. Diffuse coronary disease was
      described as: group I, narrowing greater than or equal to 50% that involved the
      entire vessel (40 patients), group II, long lesions greater than or equal to 2 cm
      in length (39 patients), group III, three or more lesions in the same vessel (19
      patients). There were 65 men and 33 women, with a mean age of 60 years; 64
      patients (65%) had unstable angina, 23 patients (23%) were diabetic, 31 (32%) had
      prior myocardial infarctions, and 12 had prior bypass surgery. Multivessel
      disease was present in 89% of patients. Angioplasty of only the diffusely
      diseased vessel was performed in 41 patients, and additional vessels were dilated
      in 57 patients. Overall, of 396 lesions (four per patient) and 197 vessels (two
      per patient) attempted, success was achieved in 382 lesions (96%) and 187 vessels
      (95%); angiographic success was achieved in 112 of 120 diffusely diseased vessels
      (93%). Clinical success was achieved in 91 patients (93%). The overall
      complication rate (death, myocardial infarction, urgent bypass surgery) was 8% (8
      of 98): six patients (6%) had myocardial infarction (one Q wave, five non-Q
      wave), one patient (1%) had urgent bypass surgery, and two patients (2%) died
      (one during bypass surgery). The majority of complications (7 of 8 or 87%),
      including the two deaths, occurred in group I patients, with a 17.5% rate, versus
      2.5% in group II and 0% in group III, p less than 0.002.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1985353
TI  - Normalization of Doppler indices of diastolic dysfunction during pacing is a sign
      of ischemic mitral regurgitation.
AB  - Twenty-three patients with angina who were undergoing diagnostic cardiac
      catheterization underwent cardiac pacing with simultaneous hemodynamic and
      Doppler echocardiographic evaluation to assess the effects of pacing-induced
      ischemic on mitral valve velocity. Seventeen patients had significant coronary
      artery disease, and six patients had normal coronary arteries. Doppler and
      hemodynamic measurements were performed at rest and immediately after pacing was
      discontinued to 91% +/- 7% of maximal predicted heart rate. Seven patients
      experienced new or significant increases in severity of mitral regurgitation
      after pacing as revealed by Doppler examination. This group had a significant
      increase (p = 0.007) in early but not in late peak filling velocities immediately
      after pacing was discontinued, with a resultant decrease in late to early ratios,
      which decreased from 1.01% +/- 0.12 to 0.70% +/- 0.19 (p = 0.006). Left
      ventricular end-diastolic pressure increased significantly from 16.7% +/- 6.8 mm
      Hg to 29.4% +/- 5.3 mm Hg after cardiac pacing (p less than 0.001). Patients with
      coronary disease who did not develop mitral regurgitation also had significant
      increases in left ventricular end-diastolic pressure from 18.7% +/- 5.8 mm Hg to
      24.3% +/- 8.6 mm Hg (p less than 0.05). There were no changes in late or early
      wave amplitude, late to early ratio, or other Doppler measurements in any of the
      other groups. We conclude that mitral regurgitation caused by pacing-induced
      myocardial ischemia normalizes Doppler indices of mitral inflow, which in turn,
      may mask persistent or worsened left ventricular diastolic dysfunction.

PMID- 1985355
TI  - High output failure in patients with peripartum cardiomyopathy: a comparative
      study with dilated cardiomyopathy.
AB  - Although few studies have reported on relatively preserved ventricular function
      in patient with peripartum cardiomyopathy, the condition is usually believed to
      have the typical low-output congestive hemodynamic pattern of the dilated
      congestive cardiomyopathies. Two groups of patients, 14 with peripartum
      cardiomyopathy and 12 with dilated congestive cardiomyopathy who were matched for
      gender and age, were studied. They had normal blood pressure and similar New York
      Heart Association functional class, nutritional status, thyroid function and
      routine laboratory evaluation. All patients were catheterized during stable in
      hospital compensation of heart failure, which was achieved by bed rest, sodium
      restriction, and administration of digoxin and diuretics long (more than 3
      months) after delivery. Significant differences (p less than 0.05) between
      patients with peripartum cardiomyopathy and those with dilated congestive
      cardiomyopathy were observed in regard to: (1) cardiac index: 3.34 +/- 1.36
      L/min/m2 versus 2.24 +/- 0.72 L/min/m2, (2) systemic vascular resistance: 1713 +/
      567 dynes.sec.cm-5 versus 2194 +/- 603 dynes.sec.cm-5, (3) right ventricular
      stroke work index: 8.6 +/- 4.2 g.M/m2 versus 14.8 +/- 8.2 g.M/m2 in the
      peripartum cardiomyopathy and the dilated congestive cardiomyopathy groups,
      respectively. Three of the patients with peripartum cardiomyopathy had resting
      cardiac index values that were even higher than the normal upper limit for our
      laboratory (4.5 L/min/m2): 4.80, 5.70, and 5.63 L/min/m2. They also had nearly
      normal left ventricular ejection fractions: 0.68, 0.41, and 0.51, respectively.
      These results indicate that, unlike the common dilated cardiomyopathy, the
      hemodynamic pattern in patients with peripartum cardiomyopathy is not
      homogeneous, and some patients have high-output failure and near normal left
      ventricular function.

PMID- 1985356
TI  - Cigarette smoking and plasma cholesterol.
AB  - Plasma cholesterol levels were determined for 51,723 participants of community
      based cholesterol screenings in 10 United States cities during 1988. Among white
      adult men and women under the age of 60 without other cardiovascular disease risk
      factors, a dose-response relationship was found between the number of cigarettes
      smoked per day and increasing levels of plasma cholesterol. In men aged 18 to 60
      years, average plasma cholesterol increased by 0.33 mg/dl for each cigarette
      smoked (p less than 0.001); in women aged 31 to 50 years, average plasma
      cholesterol increased by 0.48 mg/dl for each cigarette smoked (p less than
      0.001). Plasma cholesterol levels among ex-smokers were found to be similar to
      those of nonsmokers. No association between cigarette smoking and levels of
      plasma cholesterol was observed in men and women over age 60. Possible mechanisms
      for this observed relationship include an antiestrogenic effect of cigarette
      smoking that makes the observation more noticeable in younger female cohorts,
      enhanced lipolysis that increases levels of plasma free fatty acids, or
      differences in dietary intake between smokers and nonsmokers.

PMID- 1985358
TI  - Pulse rate, coronary heart disease, and death: the NHANES I Epidemiologic Follow
      up Study.
AB  - To determine whether associations of elevated resting pulse rate with CHD
      incidence or death in white men are independent of other risk factors and whether
      such associations exist for women and blacks, data were examined from the NHANES
      I Epidemiologic Follow-up Study. Over a follow-up period of 6 to 13 years,
      elevated RR for CHD incidence were found for older white men with baseline pulse
      greater than 84 beats/min compared with less than 74 beats/min after controlling
      multiple risk factors (RR = 1.37, 95% CL 1.02, 1.84). Risks of death from all
      causes, cardiovascular diseases, and noncardiovascular diseases were also
      elevated for white men with elevated pulse rate independent of other risk
      factors. CHD incidence was increased in white women with elevated pulse rate.
      Risks of death from all causes, cardiovascular diseases, and noncardiovascular
      diseases, were also elevated for white men with elevated pulse rate independent
      of other risk factors. CHD incidence was increased in white women with elevated
      pulse rate. Risk of death from all causes and cardiovascular diseases was
      elevated in black men and women with elevated pulse rate. Risk of death from
      noncardiovascular disease was elevated in black men with elevated pulse rate. The
      association with cardiovascular death was particularly striking in black women,
      even after adjusting for baseline risk factors (RR 3.03, 95% CL 1.46, 6.28).
      Further studies are needed to assess associations of pulse rate with CHD in
      blacks and to elucidate mechanisms in all groups.

PMID- 1985357
TI  - Side effects from amiodarone.
AB  - Amiodarone causes many side effects involving all organ systems. Although most of
      the side effects are mild and do not limit the use of the drug, there are several
      that are serious. Since many of these toxic reactions develop only after a
      prolonged period of therapy, careful follow-up on a regular basis is essential.

PMID- 1985359
TI  - Evidence for dynamic coronary vasoconstriction in the early minutes of acute
      myocardial infarction.

PMID- 1985360
TI  - Dynamic left ventricular outflow tract obstruction induced by pericardial
      tamponade during acute anterior myocardial infarction.

PMID- 1985361
TI  - Contrast echocardiographic diagnosis of PTCA-induced coronary artery-left
      ventricle fistula.

PMID- 1985362
TI  - Selective coronary arteriography via translumbar catheterization.

PMID- 1985363
TI  - Mitral valvuloplasty for life-threatening ventricular arrhythmias in mitral valve
      prolapse.

PMID- 1985365
TI  - Left ventricular hemangioma in Kasabach-Merritt syndrome.

PMID- 1985364
TI  - A randomized controlled trial of allopurinol in coronary bypass surgery.
AB  - A plethora of experimental evidence indicates that allopurinol reduces the
      formation of cytotoxic free radicals during myocardial ischemia and reperfusion.
      The purpose of this study was to evaluate the effect of allopurinol on cardiac
      performance and early mortality after coronary bypass surgery. Allopurinol (n =
      89) or placebo (n = 80) was administered to 169 patients before surgery.
      Randomization produced groups evenly matched for surgical risk factors. Hospital
      mortality rate in the placebo group was 14 of 80 (18%) in the allopurinol group 4
      of 89 (4%), p = 0.014. Cardiac performance, scored by cardiac index and the need
      for ionotropic or mechanical support, was significantly better in the allopurinol
      group. More nonfatal complications occurred in the allopurinol group. When either
      a complication or death is termed an event, the proportion of events was equal in
      the two groups. No side effects were identified. We now administer allopurinol to
      all patients who are undergoing bypass surgery unless specifically
      contraindicated.

PMID- 1985366
TI  - Pulmonary venous obstruction: utility of transesophageal echocardiography.

PMID- 1985367
TI  - Inadvertent AICD inactivation while playing bingo.

PMID- 1985368
TI  - Intrapericardial echocardiographic images and cardiac constriction.

PMID- 1985369
TI  - Midazolam nose drops for outpatient echocardiography sedation in infants.

PMID- 1985370
TI  - Composition of atherosclerotic plaques in the coronary arteries in homozygous
      familial hypercholesterolemia.

PMID- 1985371
TI  - To-and-fro left ventricular-to-right atrial shunting after valve replacement
      shown by transesophageal echocardiography.

PMID- 1985372
TI  - Aortic and mitral valve perforation: diagnosis by transesophageal
      echocardiography and Doppler color flow imaging.

PMID- 1985373
TI  - Diagnosis of postlaminectomy arteriovenous fistula using color Doppler flow
      mapping.

PMID- 1985374
TI  - The utility of echocardiography in the diagnostic strategy of postinfarction
      ventricular septal rupture: a comparison of two-dimensional echocardiography
      versus Doppler color flow imaging.
AB  - The diagnostic accuracy of Doppler color flow imaging in the diagnosis of
      postinfarction ventricular septal defects has not been established. In this
      study, 43 patients with unexplained hypotension or a new murmur in the
      periinfarct period were evaluated with conventional two-dimensional
      echocardiography and Doppler color flow imaging. The presence of a ventricular
      septal defect was confirmed by oximetry, ventriculography, operative repair, or
      autopsy in each case. Both two-dimensional and Doppler color flow imaging were
      100% specific in excluding a ventricular septal defect. Doppler color flow
      imaging correctly identified the 12 confirmed ventricular septal defects in this
      study (100% sensitivity), whereas any combination of two-dimensional criteria
      only correctly identified seven (58% sensitive) (p less than 0.05). Doppler color
      flow imaging is superior to conventional two-dimensional imaging in the diagnosis
      of a postinfarction ventricular septal defect. In addition, Doppler color flow
      imaging localized the septal defect, and thus guided therapy and technique for
      repair. Carefully performed Doppler color flow examination can exclude or result
      in the rapid diagnosis of a ventricular septal defect, which eliminates the need
      for further time-consuming confirmatory testing.

PMID- 1985375
TI  - Dipyridamole perfusion scintigraphy: the experience with its application in one
      hundred seventy patients with known or suspected unstable angina.
AB  - We evaluated the safety, accuracy, and potential clinical utility of intravenous
      dipyridamole perfusion scintigraphy with thallium-201 in 170 patients, 78 with
      suspected and 92 with known unstable angina. All had coronary angiography.
      Noncardiac side effects (26%), induced chest discomfort (44%), and ST segment
      changes (12%) were similar in the two groups. No significant arrhythmias
      occurred. Two patients had prolonged chest pain, both with extensive reversible
      image abnormalities and associated creatinine kinase-MB release. Both had
      elective bypass surgery. Twenty-eight patients had normal coronary arteries, and
      35 had single-vessel disease. Scintigraphic per patient sensitivity and
      specificity were 91% and 79% with a per vessel sensitivity of 74% and a per
      vessel specificity of 78% without between-group differences. During a brief
      follow-up period, 62 patients with image abnormalities had coronary
      revascularization, and there were seven deaths without intergroup differences. In
      a similar patient group that did not have angiography, scintigraphic defects were
      less frequent and less extensive, revascularization was not performed, and
      subsequent deaths occurred less often. Dipyridamole perfusion scintigraphy is an
      accurate alternative to exercise testing in the evaluation of patients with
      unstable angina pectoris. Although not without risk, the method appears
      relatively safe and should be considered as a guide to diagnosis, and probably to
      prognosis and management.

PMID- 1985376
TI  - Myocardial metabolic and hemodynamic effects of a sustained intravenous infusion
      of nifedipine with and without metoprolol in patients with unstable angina.
AB  - We tested the usefulness of a sustained intravenous infusion of nifedipine and a
      combination of nifedipine and metoprolol in the early management of 14 patients
      with unstable angina pectoris. After a 24-hour run-in period, nifedipine was
      titrated in a stepwise fashion (mean dose 27 +/- 7 micrograms/min). After
      nifedipine treatment coronary blood flow increased from 150 +/- 66 to 183 +/- 74
      ml/min (p less than 0.05), whereas double product, myocardial oxygen consumption,
      and both arterial and coronary sinus (nor)epinephrine levels were unchanged.
      Myocardial lactate uptake increased from 3.4 +/- 26.1 to 31.3 +/- 26.6 mumol/min
      (p less than 0.005) and free fatty acid uptake from 7.2 +/- 22.1 to 34.5 +/- 33.7
      mumol/min (p less than 0.05). A small nonsignificant improvement in amino acid
      metabolism was observed. Metoprolol was added in seven patients and led to a
      decrease in double product (-2.2 +/- 1.6 x 10(3); p less than 0.01) and
      myocardial oxygen consumption (-3.2 +/- 3.8 ml/min; p less than 0.05). The
      lactate uptake/oxygen uptake ratio increased by 18% after metoprolol (p = NS).
      The number of episodes of chest pain decreased from 2.4 +/- 1.1/24 hours to 0.1
      +/- 0.2 in the nifedipine group and from 2.9 +/- 1.1/24 hours to 0.3 +/- 0.5 in
      the nifedipine plus metoprolol group (both p less than 0.01). We conclude that in
      the acute phase of unstable angina, intravenous nifedipine can be carefully
      titrated to improve coronary blood flow and oxidative metabolism. The addition of
      metoprolol is also associated with a reduction in myocardial oxygen demand. This
      treatment results in significant hemodynamic stability.

PMID- 1985377
TI  - Incidence and clinical significance of ST segment elevation after electrical
      cardioversion of atrial fibrillation and atrial flutter.
AB  - To study the incidence and clinical significance of postshock ST segment
      elevations, we recorded 12-lead ECGs immediately after transthoracic direct
      current electrical cardioversion in 146 patients with atrial fibrillation or
      flutter. Among 23 patients (19%), acute ST segment elevations amounted to 1.4 +/-
      0.8 mV (mean +/- SD) and occurred after 243 +/- 114 joules (cumulative dose) in
      the precordial leads only in 14, concomitantly in precordial and inferior leads
      in two, and in the precordial and anterolateral leads in seven. They normalized
      within 1.5 +/- 0.8 minutes. Occurrence of ST segment elevation was related to
      previous pericardiotomy (p less than 0.00001) and age (p = 0.01). Estimation of
      myocardial enzyme release did not show evidence of myocardial damage. Patients
      with ST segment elevations had a lower conversion rate (48% versus 76%, p =
      0.005). Long-term maintenance of sinus rhythm was also diminished (35% versus
      59%, p = 0.03). Results of this study show that postcardioversion ST segment
      elevation occurs predominantly in postpericardiotomy patients and may be
      associated with an unfavorable arrhythmia prognosis.

PMID- 1985378
TI  - Study on the genesis of the double potential recorded in the high right atrium in
      atrial flutter and its role in the reentry circuit of atrial flutter.
AB  - To investigate the genesis of the double potential (DP), which is two separate
      waves, and its role in the reentry circuit of atrial flutter (AF), we performed
      overdrive pacing (ODP) from the high right atrium (HRA) in six cases of
      spontaneous AF in which the DP was recorded in the HRA. In four of the six cases,
      when the DP was arbitrarily designated D1 and D2, D1 and D2 showed progressive
      fusion during ODP. In addition, the D1 return cycle, immediately after the
      termination of ODP, corresponded to the AF cycle, and the D2 return cycle
      corresponded to the pacing cycle. This may indicate that the DP is caused by the
      collision of two directional waves. Furthermore, it is suggested that the HRA
      plays an important role in preventing a possible shortcutting of reentry waves
      and in stabilizing the reentry circuit of AF.

PMID- 1985379
TI  - Fragmented atrial activity in patients with transient atrial fibrillation.
AB  - Prediction of atrial fibrillation (AF) is very important in patients with Wolff
      Parkinson-White syndrome or in the selection of pacemaker therapeutic modality.
      In 25 patients with transient AF, the response of the atrial activity width to
      extrastimuli was examined in comparison with 25 patients without AF to see if the
      results could be used as an index of subsequent occurrence of AF. Programmed
      electrical stimulation using eight basic stimuli followed by single or double
      extrastimuli (P1P2 or P1P2P3) were delivered to the high right atrium, and the
      atrial activities were examined. The prolongation of the atrial activity caused
      by extrastimuli was termed fragmentation (Frg), and it was defined as the
      prolongation of more than 150% of the basic stimuli. Frg zone was defined as the
      zone of coupling intervals of the extrastimuli (P1P2 or P2P3) that caused Frg,
      and delta max Frg was defined as the difference between the widest Frg and the
      atrial wave width during basic stimuli. Fragmentation was reproducibly induced by
      extrastimuli, and there was an inverse relationship between Frg duration and the
      coupling interval of the extrastimuli (P1P2 or P2P3). Frg zone and delta max Frg
      were wider and longer in patients with transient AF in comparison with the
      control group for both single and double extrastimuli (p less than 0.001). AF
      inducibility using double extrastimuli was significantly high in patients with
      AF.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1985380
TI  - Increasing the yield of ventricular tachycardia induction: a prospective,
      randomized comparative study of the standard ventricular stimulation protocol to
      a short-to-long protocol and a new two-site protocol.
AB  - Programmed ventricular stimulation with a standard protocol that used up to three
      extrastimuli was compared prospectively with a short-to-long protocol and a two
      site protocol in 77 consecutive patients undergoing electrophysiologic study in
      an attempt to increase the yield of ventricular tachycardia (VT) induction. The
      short-to-long protocol uses a train of eight stimuli at a short cycle length and
      up to two extrastimuli. The two-site protocol is similar to the standard protocol
      but delivers the last extrastimulus via a second spatially separated right
      ventricular catheter. Patients were divided into two groups based on indications
      for study: group 1 included 45 patients with syncope, nonsustained VT, or both,
      and group 2 included 32 patients with a history of sustained VT, sudden cardiac
      death, or both. The yield of VT induction with the short-to-long protocol was
      less than that with the standard protocol. In none of the patients in group 1 in
      whom the standard protocol results were negative did the short-to-long protocol
      produce sustained VT. Only two patients, both in group 2, had sustained
      arrhythmias induced by the short-to-long protocol when the standard protocol
      results were negative: one had sustained VT induced and one with long QT syndrome
      had ventricular fibrillation (VF) induced with the short-to-long protocol.
      However, the short-to-long protocol failed to induce sustained VT in seven
      patients in whom the standard protocol produced sustained VT. All seven of these
      patients required three extrastimuli with the standard protocol for induction of
      VT.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1985381
TI  - Prognosis of patients with ventricular tachycardia or fibrillation and a normal
      electrophysiologic study.
AB  - The outcome of 26 patients with sustained ventricular tachycardia (n = 16) or
      ventricular fibrillation (n = 10) and no inducible ventricular tachycardia (less
      than or equal to 10 beats) by baseline programmed stimulation was studied.
      Coronary artery disease was present in 14 patients, dilated cardiomyopathy was
      seen in seven, valvular heart disease was present in two, and no apparent cardiac
      abnormalities were found in three. The mean left ventricular ejection fraction
      was 53 +/- 14%. During the follow-up period of 24 +/- 16 months, actuarial
      survival rates at 1 and 2 years were 95% and 89% for sudden death and 95% and 83%
      for total cardiac death, respectively. No patients with a known ejection fraction
      greater than 30% died suddenly during the follow-up. Noninducibility by
      programmed stimulation in patients with sustained ventricular tachycardia or
      fibrillation is associated with a relatively preserved ventricular function. It
      may predict a low risk of sudden death in patients with preserved ventricular
      function.

PMID- 1985382
TI  - Syncope of unknown origin: clinical, noninvasive, and electrophysiologic
      determinants of arrhythmia induction and symptom recurrence during long-term
      follow-up.
AB  - Ninety-one consecutive patients with syncope of unknown origin underwent
      electrophysiologic studies (EPS). Univariate analysis identified the following
      variables: age, + signal-averaged ECG (SAECG), left ventricular ejection fraction
      (LVEF), history of myocardial infarction, coronary artery disease, left
      ventricular aneurysm, and history of sustained monomorphic ventricular
      tachycardia (SMVT) on Holter; multivariate analysis identified +SAECG, LVEF, and
      history of SMVT as risk factors for induction of SMVT at EPS. All patients were
      followed up for 19.0 +/- 8.3 months and 17 had recurrence of syncope. Patients
      were divided into empiric, EP-guided, and no therapy groups. The EP-guided
      therapy group included all patients with SMVT at EPS. Recurrence rates among all
      three groups were similar. We conclude that: (1) Patients who have inducible SMVT
      at EPS can be identified using certain clinical and noninvasive variables. When
      these patients undergo EP-guided therapy, their rate of recurrence of syncope
      becomes compatible with that of patients who had no arrhythmia induced at EPS.
      (2) Empiric therapy does not offer any benefit over no therapy in reducing the
      rate of recurrent of scope.

PMID- 1985383
TI  - Electrocardiographic and antiarrhythmic effects of intravenous amiodarone:
      results of a prospective, placebo-controlled study.
AB  - The antiarrhythmic efficacy of intravenously administered amiodarone was examined
      in a prospective, randomized, placebo-controlled study that involved 77 patients
      after coronary artery bypass surgery. Amiodarone was given after surgery in a
      loading bolus of 300 mg for 2 hours followed by 1200 mg every 24 hours for 2 days
      and 900 mg every 24 hours for the next 2 days. Amiodarone suppressed both
      supraventricular and ventricular arrhythmias within 12 hours after the start of
      therapy. Particularly, the incidence of atrial fibrillation (5% vs 21% in the
      control group; p less than 0.05) and of nonsustained ventricular tachycardia (3%
      vs 16%; p less than 0.05) was reduced by amiodarone. Heart rate was slowed (p
      less than 0.001) and repolarization--as judged by JTc interval--was prolonged
      compared with the control group (p less than 0.01). In two patients, amiodarone
      infusion was stopped because of excessive QTc prolongation. No detrimental
      hemodynamic effects of the drug were observed. Thus the intravenous
      administration of amiodarone appears to be suitable for patients in whom rapid
      suppression of symptomatic supraventricular and ventricular arrhythmias is
      warranted in the presence of left ventricular dysfunction.

PMID- 1985384
TI  - Electrophysiologic characteristics of manifest and latent retrograde conduction
      in dogs.
AB  - Atrioventricular (AV) nodal reentry requires intact retrograde ventriculoatrial
      (VA) conduction. The purpose of this study was to assess the contribution of
      various pacing and pharmacologic techniques to uncover VA conduction during
      apparent unidirectional VA block, and to evaluate the role of several biologic
      and electrophysiologic factors in concealment of retrograde conduction. Forty
      healthy dogs underwent catheter-electrophysiologic studies of AV and VA
      conduction. Group I (20 animals) had intact VA conduction. Group II (six animals)
      had VA dissociation with ventricular pacing initiated during sinus rhythm, but
      the presence of VA conduction was confirmed by isoproterenol infusion or by
      premature ventricular stimulation. In group III (14 animals), the above
      techniques failed to uncover VA conduction. Eight of 14 group III animals
      underwent thoracotomy and crushing or freezing of the sinoatrial (SA) node.
      Ventricular pacing initiated during sinus standstill was associated with 1:1 VA
      conduction in each experiment. VA conduction time and retrograde Wenckebach cycle
      length, both in the baseline state and during isoproterenol infusion, were
      significantly longer in the eight animals in group III than in those in group I.
      Age, gender, weight, breed, sinus cycle length, and anterograde AV conduction
      properties were not significantly different between groups I, II, and III. The
      data suggest that (1) in normal dogs, complete unidirectional VA block probably
      does not exist; (2) in the presence of anterograde input to the AV node, even
      sophisticated pacing and pharmacologic maneuvers may fail to uncover the presence
      of VA conduction; (3) although anterograde input is essential for concealment of
      VA conduction, the phenomenon is more closely associated with depressed
      retrograde than with anterograde AV nodal characteristics.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1985385
TI  - Cardiovascular disease risk profiles.
AB  - This article presents prediction equations for several cardiovascular disease
      endpoints, which are based on measurements of several known risk factors.
      Subjects (n = 5573) were original and offspring subjects in the Framingham Heart
      Study, aged 30 to 74 years, and initially free of cardiovascular disease.
      Equations to predict risk for the following were developed: myocardial
      infarction, coronary heart disease (CHD), death from CHD, stroke, cardiovascular
      disease, and death from cardiovascular disease. The equations demonstrated the
      potential importance of controlling multiple risk factors (blood pressure, total
      cholesterol, high-density lipoprotein cholesterol, smoking, glucose intolerance,
      and left ventricular hypertrophy) as opposed to focusing on one single risk
      factor. The parametric model used was seen to have several advantages over
      existing standard regression models. Unlike logistic regression, it can provide
      predictions for different lengths of time, and probabilities can be expressed in
      a more straightforward way than the Cox proportional hazards model.

PMID- 1985386
TI  - Antioxidant nutrients and disease prevention: an overview.
AB  - Interest in free radical events has stimulated speculation that their disorder
      may be involved in a number of diseases. The reduction of dioxygen to water
      involves several active intermediates. The control of this depends on the
      integrity of an enzymatic system that requires adequate intake of selenium,
      copper, zinc, and manganese; if their level of intake is low, proliferation of
      active oxygen metabolites may occur. Targets for attack are DNA, proteins, and
      polyunsaturated phospholipids. Peroxidation of polyunsaturated phospholipids will
      result in disruption of membrane architecture. Vitamin E, perhaps with ascorbic
      acid, can prevent this, and vitamin A and beta-carotene also intervene. The
      implication of this in the etiology of a number of diseases depends on theory and
      on evidence linking low intake of the antioxidant nutrients with a high disease
      incidence. Improvements in epidemiology have resulted in glimpses into what may
      prove to be links between diet and disease.

PMID- 1985387
TI  - Antioxidant defense systems: the role of carotenoids, tocopherols, and thiols.
AB  - Reactive oxygen species occur in tissues and can damage DNA, proteins,
      carbohydrates, and lipids. These potentially deleterious reactions are controlled
      by a system of enzymatic and nonenzymatic antioxidants which eliminate
      prooxidants and scavenge free radicals. The ability of the lipid-soluble
      carotenoids to quench singlet molecular oxygen may explain some anticancer
      properties of the carotenoids, independent of their provitamin A activity.
      Tocopherols are the most abundant and efficient scavengers of hydroperoxyl
      radicals in biological membranes. Water-soluble antioxidants include ascorbate
      and cellular thiols. Glutathione is an important substrate for enzymatic
      antioxidant functions and is capable of nonenzymatic radical scavenging. Thiols
      associated with membrane proteins may also be important to the antioxidant
      systems. Interactions between the thiols, tocopherols, and other compounds
      enhance the effectiveness of cellular antioxidant defense.

PMID- 1985388
TI  - Membrane damage due to lipid oxidation.
AB  - The influence of free radical-mediated oxidations is amplified because it
      proceeds by a chain mechanism, ie, only one radical can initiate chain reaction
      which may propagate over and over again. It was found that the in vitro
      oxidations of erythrocyte membranes proceed by a chain mechanism with a long
      kinetic chain length. Thus, the role of chain-breaking antioxidants is quite
      important, since they scavenge chain-carrying radicals to break a chain reaction.
      In fact, it has been found experimentally that vitamin E, a lipophilic chain
      breaking antioxidant present within the membranes, suppresses the oxidative
      damage of the membranes more efficiently than water-soluble chain-breaking
      antioxidants such as vitamin C, which scavenges aqueous radicals but can not
      scavenge chain-carrying radicals within the membranes.

PMID- 1985389
TI  - Oxidation of lipoproteins and atherosclerosis.
AB  - The fatty streak is the earliest lesion of atherosclerosis. This lesion contains
      foam cells which are primarily derived from blood monocytes. The accumulation of
      cholesterol in macrophages is explained by the uptake of modified low-density
      lipoprotein (LDL). An in vivo modification of lipoproteins might be oxidation.
      The oxidized LDL showed several chemicophysical modifications. The first
      demonstrated effect of LDL oxidation was its increased susceptibility to uptake
      by cultured macrophages. Furthermore, oxidized LDL exhibits a chemotactic
      activity, and a cytotoxicity. An hypothesis that explains the appearance and
      development of atherosclerotic lesions and is based on obtained in vitro is
      exposed. LDL-like lipoproteins extracted from human aorta had some of properties
      of oxidized LDL, such as the recognition of materials present in atheroma by
      antibodies against oxidized LDL and the presence of autoantibodies against
      oxidized LDL in human sera are in favor of the pathogenetically important role of
      the oxidation of LDL.

PMID- 1985390
TI  - Vitamin E in gastric mucosal injury induced by ischemia-reperfusion.
AB  - To clarify the relationship among vitamin E, oxygen radicals, and lipid
      peroxidation in ischemia-reperfusion, we produced an experimental model of
      gastric mucosal injury in rats by ischemia-reperfusion with clamping of the
      celiac artery and measurements of the area of gastric erosion, thiobarbituric
      acid (TBA)-reactive substances, and alpha-tocopherol in serum and gastric mucosa
      during ischemia-reperfusion. The area of gastric erosions and TBA-reactive
      substances in gastric mucosa were significantly increased after 30 and 60 min of
      reperfusion. The serum alpha-tocopherol-cholesterol ratio and gastric mucosal
      alpha-tocopherol were significantly decreased after 30 and 60 min of reperfusion.
      On the other hand, in vitamin E-deficient rats, gastric mucosal injury induced by
      ischemia-reperfusion was more severe than that in vitamin E-nondeficient rats.
      These results indicate that vitamin E is consumed in the process of lipid
      peroxidation induced by oxygen radicals in ischemia-reperfusion to prevent the
      development of tissue damage.

PMID- 1985391
TI  - Human carcinogenesis--introductory remarks.

PMID- 1985392
TI  - Nutritional approach to cancer prevention with emphasis on vitamins,
      antioxidants, and carotenoids.
AB  - The main human cancers are associated with complex life-style related causative,
      enhancing, and inhibiting factors. Tobacco smoking or chewing exposes humans to
      genotoxic carcinogens and to promoting substances. Likewise, Western dietary
      traditions involve certain carcinogens and promoters, whereas Oriental traditions
      implicate other carcinogens and promoters. Importantly, in virtually all
      situations regular intake of fruits and vegetables appreciably lowers the risk of
      cancer. This paper reviews the causes of the main human cancers and analyzes the
      mechanisms of the protective effects of fruits and vegetables. Prevention of
      human cancer requires the definition of optimal levels of recommended daily
      allowances of micronutrients.

PMID- 1985393
TI  - Effects of carotenoids in cellular and animal systems.
AB  - It has been suggested that carotenoid pigments may function as chemopreventive
      agents for reducing the risk of cancer in humans. Part of this suggestion rests
      on epidemiological evidence, and part rests on work done in cellular and animal
      systems. In this article, the experimental evidence for carotenoid inhibition of
      mutagenicity, malignant transformation, tumor formation, and immunoenhancement is
      reviewed. Although a mechanism for these effects cannot yet be identified, it is
      clear that the overwhelming evidence in these systems would indicate that
      carotenoids exert an important influence in modulating the actions of
      carcinogens.

PMID- 1985394
TI  - Inhibition of nitrosamine formation by ascorbic acid.
AB  - Nitrosation occurs under a wide variety of conditions by reaction of most types
      of amines with any of a large number of nitrosating species. Nitrite can be
      formed in vivo via bacterial reduction of nitrate and by activated macrophages
      and endothelial cells. The mechanism of nitrite formation by mammalian cells is
      via enzymatic oxidation of arginine to NO followed by oxidation to N2O3 and N2O4.
      Nitrosatable amines are found in many foods and some, eg, dimethylamine, are
      synthesized in the body. Precursors of N-nitroso compounds are thus almost
      constantly present together under favorable reaction conditions in vivo and there
      is, consequently, considerable interest concerning possible human health risks
      arising from endogenous formation of this class of compounds. Among many
      nitrosation inhibitors, most attention has focused on ascorbic acid, which reacts
      with many nitrosating agents and which is virtually nontoxic. This presentation
      discusses the chemistry of ascorbic acid inhibition of nitrosation reactions.

PMID- 1985395
TI  - Vegetables, fruits, and carotenoids and the risk of cancer.
AB  - Low intake of vegetables, fruits, and carotenoids is consistently associated with
      increased risk of lung cancer in both prospective and retrospective studies. In
      addition, low levels of beta-carotene in serum or plasma are consistently
      associated with the subsequent development of lung cancer. The simplest
      explanation is that beta-carotene is protective. Since retinol (preformed vitamin
      A) is not related in a similar manner to lung cancer risk, beta-carotene appears
      to function through a mechanism that does not require conversion into vitamin A.
      However, the importance of other carotenoids and other constituents of vegetables
      and fruit has not been adequately explored. Both prospective and retrospective
      studies suggest that vegetable and fruit intake may reduce the risk of cancers of
      the mouth, pharynx, larynx, esophagus, stomach, colon, rectum, bladder, and
      cervix. But because of fewer studies and less consistency among studies, the
      epidemiologic evidence is at present less persuasive than for lung cancer.

PMID- 1985396
TI  - Prediagnostic serum levels of carotenoids and vitamin E as related to subsequent
      cancer in Washington County, Maryland.
AB  - In 1974 and 1975, serum specimens were collected from 25,802 volunteers in
      Washington County, Maryland. The serum was kept frozen at -73 degrees C until the
      time of assay. Prediagnostic samples from 436 cancer cases and 765 matched
      control subjects have been assayed. Nine sites have been studied: colon, rectum,
      pancreas, lung, melanoma, basal cell of skin, breast, prostate, and bladder.
      Serum beta-carotene levels showed a strong protective association with lung
      cancer, suggestive protective associations with melanoma and bladder cancer, and
      a suggestive but nonprotective association with rectal cancer. Serum vitamin E
      levels had a protective association with lung cancer; none of the other sites
      showed impressive associations. Low levels of serum lycopene were strongly
      associated with pancreatic cancer and less strongly associated with cancer of the
      bladder and rectum.

PMID- 1985398
TI  - Vitamin C and cancer prevention: the epidemiologic evidence.
AB  - Epidemiologic evidence of a protective effect of vitamin C for non-hormone
      dependent cancers is strong. Of the 46 such studies in which a dietary vitamin C
      index was calculated, 33 found statistically significant protection, with high
      intake conferring approximately a twofold protective effect compared with low
      intake. Of 29 additional studies that assessed fruit intake, 21 found significant
      protection. For cancers of the esophagus, larynx, oral cavity, and pancreas,
      evidence for a protective effect of vitamin C or some component in fruit is
      strong and consistent. For cancers of the stomach, rectum, breast, and cervix
      there is also strong evidence. Several recent lung cancer studies found
      significant protective effects of vitamin C or of foods that are better sources
      of vitamin C than of beta-carotene. It is likely that ascorbic acid, carotenoids,
      and other factors in fruits and vegetables act jointly. Increased consumption of
      fruits and vegetables in general should be encouraged.

PMID- 1985397
TI  - Beta-carotene and cancer prevention: the Basel Study.
AB  - In 1971-1973 at the third examination of the Basel Study started in 1959, the
      major antioxidant vitamins and carotene were measured in the plasma of 2974 men.
      A subsample and their families were reinvestigated in 1977-79. During the 12-y
      observation period (1973-85) 553 men died, 204 of cancer (lung cancer 68, stomach
      cancer 20; colon cancer 17, all other malignancies 99). We found significantly
      lower mean carotene levels for all cancer, bronchus cancer, and stomach cancer
      (all P less than 0.01) compared with the 2421 survivors. The relative risk of
      subjects with low carotene (less than 0.23 mumol/L) was significantly elevated (P
      less than 0.05) for lung cancer (Cox's model). Higher risks were noted for all
      cancer (P less than 0.01) if both carotene and retinol were low. Low plasma
      carotene which is known to reflect carotene intake is in our study associated
      with increased cancer risk.

PMID- 1985399
TI  - Vitamin E and cancer prevention.
AB  - Some animal experiments and human studies suggest that vitamin E may protect
      against cancer. Serum alpha-tocopherol concentration was studied for its
      prediction of cancer in a cohort of 36,265 adults in Finland. During a mean
      follow-up of 8 y, cancer was diagnosed in 766 persons. The levels of serum alpha
      tocopherol were determined from stored serum samples (at -20 degrees C) taken
      from these cancer patients and from 1419 matched control subjects. Individuals
      with a low level of alpha-tocopherol had about a 1.5-fold risk of cancer compared
      with those with a higher level. The strength of the association between serum
      alpha-tocopherol level and cancer risk varied for different cancer sites and was
      strongest for some gastrointestinal cancers and for the combined group of cancers
      unrelated to smoking. The association was strongest among nonsmoking men and
      among women with low levels of serum selenium. The findings agree with the
      hypothesis that dietary vitamin E in some circumstances protects against cancer.

PMID- 1985400
TI  - Gastric juice ascorbic acid: effects of disease and implications for gastric
      carcinogenesis.
AB  - N-nitroso compounds (NOC) are strongly implicated in the causation of cancer of
      the stomach and it has been suggested that ascorbic acid might reduce the risk of
      gastric cancer by preventing their formation within gastric juice. However, until
      recently there have been no measurements of gastric juice ascorbic acid
      concentrations. We have measured both gastric juice ascorbic and total vitamin C
      (ascorbic acid and dehydroascorbic acid). Our findings suggest that ascorbic acid
      is secreted into the gastric lumen so that gastric juice concentrations are often
      greater than those in plasma. Gastric pathology affects this secretion, leading
      to values in gastric juice that are lower than plasma levels. Stimulation of
      gastric secretion does not raise vitamin C concentrations in individuals whose
      values are initially low. The role of ascorbic acid in preventing formation of
      NOC and protecting against gastric cancer is discussed in the light of these
      findings.

PMID- 1985401
TI  - Potential role of beta-carotene in prevention of oral cancer.
AB  - Recent data suggests that retinoids and carotenoids may be effective in reversing
      a putative "field cancerization" defect in the epithelium at risk for oral
      cancer. Animal experiments have shown that these compounds can inhibit cancer
      formation. Several clinical trials have demonstrated the ability of retinoids to
      reverse oral leukoplakia. However, toxicities associated with retinoids at the
      doses used in these studies limits their potential for chemoprevention. Because
      of its lack of toxicity, beta-carotene is a very attractive agent for
      chemoprevention. It suppresses micronuclei in exfoliated oral mucosal cells from
      subjects at risk for oral cancer and recently has been shown to be active in
      reversing leukoplakia. Another area under investigation is the possibility of
      preventing second primary tumors in patients cured of their initial cancer who
      have an increased risk of developing new cancers of the upper acrodigestive
      tract.

PMID- 1985402
TI  - Remission of precancerous lesions in the oral cavity of tobacco chewers and
      maintenance of the protective effect of beta-carotene or vitamin A.
AB  - Participants in the intervention trials were fishermen (Kerala, India), who
      chewed tobacco-containing betel quids daily before and throughout the study
      period. Frequency of oral leukoplakia, micronuclei in oral mucosal cells, and
      alterations in nuclear textures were used as endpoints. Administration of vitamin
      A (60 mg/wk) for 6-mo resulted in complete remission of leukoplakias in 57% and a
      reduction of micronucleated cells in 96% of tobacco-chewers. beta-carotene (2.2
      mmol/wk) induced remission of leukoplakia in 14.8% and reduction of
      micronucleated cells in 98%. Vitamin A completely suppressed and beta-carotene
      suppressed by 50% formation of new leukoplakia within the 6-mo trial period.
      After withdrawal of vitamin A or beta-carotene treatment, oral leukoplakias
      reappeared, frequency of micronuclei in oral mucosa increased, and nuclear
      textures reverted to those present before the administration of chemo-preventive
      agents. The protective effect of the original treatment could be maintained for
      at least 8 additional months by administration of lower doses of vitamin A or
      beta-carotene.

PMID- 1985403
TI  - Studies evaluating antioxidants and beta-carotene as chemopreventives.
AB  - Cancer chemoprevention research takes leads from epidemiologic and laboratory
      research and develops them through in vitro and in vivo preclinical research and
      initial human studies into randomized controlled clinical trials. At present, the
      chemoprevention program is sponsoring 21 human efficacy studies. These trials are
      testing the potential of agents (beta-carotene, folic acid, 13-cis retinoic acid,
      4-hydroxyphenyl retinamide, vitamins C and E, and minerals) as inhibitors of a
      variety of cancers in humans (colon, lung, esophagus, cervix, bladder, and skin).
      Endpoints in these studies include overall incidence of cancer, incidence of
      specific cancers, rate of regression or progression of preneoplastic changes, and
      changes in cellular or biochemical parameters. Study participants include
      volunteers from the general population; populations at high risk for cancer
      because of occupation, lifestyle, or place of residence; persons with previously
      treated cancers; and persons with preneoplastic lesions. Study designs include
      single agent randomization, combination of agents and complete factorial designs.

PMID- 1985404
TI  - Role of vitamin E in preventing the oxidation of low-density lipoprotein.
AB  - The fatty acid composition, antioxidants, and the oxidation resistance of the low
      density lipoproteins (LDL) from a number of different donors were determined. The
      oxidation resistance of LDL, as determined in vitro by the duration of the lag
      phase in copper ion-induced oxidation, did not correlate with the alpha
      tocopherol content of the LDL. By supplementating plasma with vitamin E, the
      alpha-tocopherol content of LDL could be increased from approximately 9 to 30
      mol/mol LDL and also the oxidative resistance increased nearly linearly with
      increasing alpha-tocopherol content. The results indicate that alpha-tocopherol
      is an important, yet not the only parameter that determines the oxidation
      resistance of LDL.

PMID- 1985405
TI  - Vitamin C and cardiovascular risk factors.
AB  - The concept that ascorbic acid (vitamin C) supplementation protects against
      coronary heart disease developed in the late 1970s when vitamin C intakes in
      industrialized nations were lower than at present. Supplementation was then shown
      to lower plasma total cholesterol and, among some elderly men, to raise high
      density lipoprotein cholesterol. However, among people in initially good vitamin
      C nutriture, these effects are usually not seen. In five populations of
      essentially healthy people, blood pressure has been found to correlate negatively
      with vitamin C status. Recently, in a placebo-controlled, double-blinded study,
      extra ascorbic acid for 6 wk was observed to lower systolic and pulse pressure in
      a small group of borderline hypertensive subjects.

PMID- 1985406
TI  - Inverse correlation between plasma vitamin E and mortality from ischemic heart
      disease in cross-cultural epidemiology.
AB  - Essential antioxidants were determined in plasma of middle-aged men representing
      16 European study populations, which differed sixfold in age-specific mortality
      from ischemic heart disease (IHD). In 12 populations with "common" plasma
      cholesterol (5.7-6.2 mmol/L) and blood pressure, both classical risk factors
      lacked significant correlations to IHD mortality, whereas absolute levels of
      vitamin E (alpha-tocopherol) showed a strong inverse correlation (r2 = 0.63, P =
      0.002). Evaluating all populations, cholesterol and diastolic blood pressure were
      moderately associated, but their correlation was inferior to that of vitamin E.
      In stepwise regression and multiple regression analysis, mortality was
      predictable to 62% by lipid-standardized vitamin E, to 79% by vitamin E and
      cholesterol, to 83% after inclusion of lipid-standardized vitamin A (retinol),
      and to 87% by all the above parameters plus blood pressure. Thus, in the present
      study the cross-cultural differences of IDH mortality are primarily attributable
      to plasma status of vitamin E, which might have protective functions.

PMID- 1985407
TI  - Scientific basis for medical therapy of cataracts by antioxidants.
AB  - Cataract is one of the major causes of age-dependent visual impairment and
      blindness. The geographic distribution of cataract is known to be associated with
      the intensity and duration of sunlight--especially of the ultraviolet frequency-
      at particular places. Exposure of animals and humans to oxygen has also been
      known to result in cataract formation. Studies described in this communication
      indicate that the ocular lens is physiologically damaged when exposed to an
      environment of active species of oxygen, commonly referred to as oxyradicals.
      Several photochemical and nonphotochemical models have been described. The
      results suggest that an intraocular generation of active oxygen may constitute a
      significant risk factor in the overall pathogenesis of senile cataracts. The
      cataractogenic effect of oxyradicals, however, can be thwarted by nutritional and
      metabolic antioxidants such as ascorbate, vitamin E, and pyruvate. These agents,
      therefore, may be useful for prophylaxis or therapy against cataracts.

PMID- 1985408
TI  - A possible role for vitamins C and E in cataract prevention.
AB  - Biochemical evidence suggests that oxidative stress caused by accumulation of
      free radicals is involved in the pathogenesis of senile cataracts. If so,
      appropriate amounts of the antioxidant vitamins C and E might be expected to
      prevent or retard the process. Such activity has been observed in several in
      vitro and in vivo studies of experimentally-induced cataracts. A recent
      epidemiologic study found that cataract patients tended to have lower serum
      levels of vitamins C, E, or carotenoids than did control subjects. The present
      investigation, which compared the self-reported consumption of supplementary
      vitamins by 175 cataract patients with that of 175 individually matched, cataract
      free subjects, revealed that the latter group used significantly more
      supplementary vitamins C and E (P = 0.01 and 0.004, respectively). Because the
      results suggested a reduction in the risk of cataracts of at least 50%, a
      randomized, controlled trial of vitamin supplementation in cataract prevention
      may be warranted.

PMID- 1985409
TI  - Epidemiologic evidence of a role for the antioxidant vitamins and carotenoids in
      cataract prevention.
AB  - The relationship between antioxidant nutrient status and senile cataract was
      examined in 77 subjects with cataracts and 35 control subjects with clear lenses.
      Subjects with low (below the 20th percentile) and moderate (20th-80th
      percentiles) plasma nutrient and nutrient intake levels of vitamin C, vitamin E,
      and carotenoids were compared with subjects with high levels (above the 80th
      percentile). The odds ratio (OR) of cortical (CX) cataract among subjects with
      low plasma carotenoid levels was 7.2 (P less than 0.05) and the OR of posterior
      subcapsular (PSC) cataract for persons with low plasma vitamin C was 11.3 (P less
      than 0.10). Low vitamin C intake was associated with an increased risk of CX (OR
      = 3.7, P less than 0.10) and PSC (OR = 11.0, P less than 0.05) cataract. Subjects
      who consumed fewer than 3.5 servings of fruit or vegetables per day had an
      increased risk of both CX (OR = 5.0, P less than 0.05) and PSC cataract (OR =
      12.9, P less than 0.01).

PMID- 1985410
TI  - Dietary guidelines and the results of food consumption surveys.
AB  - This review focuses on dietary guidelines regarding fruit and vegetable
      consumption; sources of the antioxidant micronutrients, beta-carotene and vitamin
      C; and survey data on the US population's actual consumption of these foods. The
      Dietary Guidelines for Americans recommended consumption of five or more servings
      of vegetables and fruits daily, as did the 1989 Diet and Health report, which
      also emphasized fruits and vegetables rich in vitamin C and carotenoids. In
      contrast with these recommendations and strong evidence for a beneficial effect,
      very few individuals in the United States even approach the recommended levels of
      intake. In the US NHANES II data, 41% of the population had no fruit on the
      survey day; only one fourth had a fruit or vegetable rich in vitamin A or in
      vitamin C. Only 10% consumed the recommended five servings. Efforts to increase
      consumption of these foods are needed to improve the diet and health of the
      population.

PMID- 1985411
TI  - Assessment of the roles of vitamin C, vitamin E, and beta-carotene in the
      modulation of oxidant stress mediated by cigarette smoke-activated phagocytes.
AB  - Phagocyte-derived reactive oxidants have been increasingly implicated in
      inflammation-related tissue injury and carcinogenesis. Cigarette smoking is a
      useful human model of chronic inflammation since it is uncomplicated by
      chemotherapy. It has been utilized to investigate both the involvement of
      phagocyte-derived reactive oxidants in the pathogenesis of pulmonary dysfunction
      and carcinogenesis, as well as the possible role of nutritional antioxidants in
      the prevention of oxidant-mediated tissue damage. Reactive oxidants generated by
      activated phagocytes appear to be primary mediators of spirometric abnormalities
      in cigarette smokers. Cigarette smoking is also associated with decreased plasma
      levels of ascorbate and beta-carotene, which indicates that the smoking-related
      chronic inflammatory response leads to an imbalance of oxidant/antioxidant
      homeostasis and possible predisposition to oxidant-inflicted tissue damage and
      disease.

PMID- 1985412
TI  - Oxidative damage to lipids within the inflamed human joint provides evidence of
      radical-mediated hypoxic-reperfusion injury.
AB  - Previous work has established the existence of a pathophysiological environment
      within the inflamed human joint, capable of sustaining a hypoxic-reperfusion
      event. Using four different assay systems (two standard and two novel) applied to
      synovial fluid for the assessment of lipid peroxidation, a series of studies
      demonstrate that exercise of the inflamed human knee promotes radical-mediated
      lipid peroxidation within the joint. The implication for novel antioxidant
      therapeutic approaches to inflammatory joint disease is discussed.

PMID- 1985413
TI  - Vitamin E supplementation and periventricular hemorrhage in the newborn.
AB  - In a randomized controlled trial preterm babies received 20 mg vitamin E/kg im
      soon after birth (day 0) and at 24 and 48 h. The mean +/- SD plasma vitamin E
      level on day 0 was identical in supplemented and control groups (9.98 +/- 4.88
      mumol/L) and rose progressively only in supplemented babies reaching a peak of
      69.2 +/- 21.36 mumol/L at 72 h. Supplemented babies had a lower incidence of
      intraventricular hemorrhage (IVH) diagnosed by ultrasound (9/102, 8.8%) than the
      control group (37/108, 34.3%; 95% CI for difference in incidence, 15-36%). In a
      subsequent uncontrolled study using the same vitamin E preparation, a single dose
      of 20 mg/kg was given soon after birth to preterm babies. The peak mean +/- SD
      plasma level was 32.97 +/- 13.47 mumol/L at 48 h. The incidence of IVH (16/121,
      13.2%) was lower than in historical control from the randomized trial (95% CI for
      difference; 10.2-31.8%) in spite of the single-dose group having more clinical
      risk factors for IVH. We conclude that vitamin E protects against IVH in preterm
      babies.

PMID- 1985414
TI  - Antioxidants and aging.
AB  - Aging in mammalian species appears to be the result of normal developmental and
      metabolic processes. In spite of the vast complexity of aging processes,
      relatively less complex processes such as longevity determinant genes (LDGs) may
      exist governing aging rate. Much experimental data exists indicating a causative
      role of oxyradicals in aging processes. In testing the hypothesis that
      antioxidants may represent LDGs, a positive correlation in the tissue
      concentration of specific antioxidants with life span of mammals was found. These
      antioxidants include superoxide dismutase, carotenoids, alpha-tocopherol, and
      uric acid. We also found that the resistance of tissues to spontaneous
      autoxidation and the amount of oxidative damage to DNA correlates inversely with
      life span of mammals. These results suggest a role of oxyradicals in causing
      aging and that the antioxidant status of an individual could be important in
      determining frequency of age-dependent diseases and duration of general health
      maintenance.

PMID- 1985415
TI  - An open trial of high-dosage antioxidants in early Parkinson's disease.
AB  - High dosages of tocopherol and ascorbate were administered to patients with early
      Parkinson's disease as a preliminary open-labeled trial for the eventual
      controlled double-blind study evaluating antioxidants as a test of the endogenous
      toxin hypothesis of the etiology of Parkinson's disease. The primary endpoint of
      the trial was the need to treat patients with levodopa. The time when levodopa
      became necessary in the treated patients was compared with another group of
      patients followed elsewhere and not taking antioxidants. The time when levodopa
      became necessary was extended by 2.5 y in the group taking antioxidants. The
      results of this pilot study suggest that the progression of Parkinson's disease
      may be slowed by the administration of these antioxidants. A large multicenter,
      controlled clinical trial currently underway in North America evaluating
      tocopherol and deprenyl has the potential to confirm these results.

PMID- 1985416
TI  - Antioxidant vitamins and beta-carotene: effects on immunocompetence.
AB  - Adequacy or deficiency in the micronutrient status of an individual deeply
      affects its immunocompetence. Among the different micronutrients, antioxidative
      vitamins and beta-carotene are particularly effective in modulating immune
      functions and host defense against microorganisms or other invasive processes.
      This involves antigen-specific humoral or cell-mediated reactions of the immune
      system as well as nonspecific inflammatory processes. Owing to the interactions
      between micronutrient status and immunocompetence, the assessment of the
      micronutrient status of an individual can help to predict the risk of specific
      diseases associated with a deficient or suppressed immunocompetence, eg,
      infection or cancer. By the appropriate intervention it should be possible to
      modify this risk as has been shown in a number of carefully controlled studies.
      Assessment of the immunocompetence of an individual by measuring a limited number
      of key parameters of the immune system can help in the very early detection of
      specific micronutrient deficiencies.

PMID- 1985417
TI  - Premalignant lesions: role of antioxidant vitamins and beta-carotene in risk
      reduction and prevention of malignant transformation.
AB  - Epidemiological studies have shown that diets rich in one or more antioxidant
      nutrients may reduce the risk of cancers of the lung, uterine cervix, mouth, and
      gastrointestinal tract. Study of premalignant lesions offers a comparatively
      expedient approach to identifying and evaluating the efficacy of the cancer
      chemopreventive components of foods. Some recent findings suggest roles for beta
      carotene and/or vitamin C in reversing or reducing the risk of cervical dysplasia
      and oral leukoplakia. There are some indications that vitamin C and beta-carotene
      may reduce the risk of atrophic gastritis and gastric cancer. Additional
      epidemiological and molecular biology studies and clinical intervention trials
      using premalignant lesions as the marker of specific cancer risks should become
      an important component of future research in the area of cancer chemoprevention.

PMID- 1985418
TI  - The antioxidant nutrients and disease prevention--what do we know and what do we
      need to find out?

PMID- 1985419
TI  - AJDC is 80 years old. From pedology to pediatrics.

PMID- 1985420
TI  - Radiological case of the month. Neonatal appendicitis with perforation.

PMID- 1985421
TI  - Picture of the month. Lowe's syndrome.

PMID- 1985422
TI  - Characteristics of perinatal cocaine-exposed infants with necrotizing
      enterocolitis.

PMID- 1985423
TI  - Current social practices leading to water intoxication in infants.

PMID- 1985424
TI  - Alkaline urine is associated with eating disorders.

PMID- 1985425
TI  - Major congenital neurologic malformations.

PMID- 1985426
TI  - Status report on phenylketonuria treatment: 1990.

PMID- 1985427
TI  - Development, growth, and cardiac surgery.

PMID- 1985428
TI  - Intellectual development in 12-year-old children treated for phenylketonuria.
AB  - Intelligence and achievement test scores were evaluated for 95 12-year-old
      children with phenylketonuria who had begun dietary therapy during the neonatal
      period. Dietary control of blood phenylalanine below 900 mumol/L was maintained
      beyond age 10 years in 23 children; 72 others had blood phenylalanine
      persistently above that level at ages ranging from 18 months to 10 years. Test
      scores at age 12 years were negatively correlated with the age at initiation of
      diet and with blood phenylalanine levels from ages 4 to 10 years, and positively
      correlated with parent IQ scores and the age at loss of dietary control. Children
      who maintained phenylalanine levels below 900 mumol/L beyond age 10 years showed
      no deficits in test scores, except for arithmetic, the scores of which declined
      between ages 6 and 12 years in 90% of the children in this study. These data
      strongly support a recommendation that dietary restriction of phenylalanine
      should be maintained through adolescence.

PMID- 1985429
TI  - Women in medicine. Fantasies, dreams, myths, and realities.

PMID- 1985430
TI  - Lumbar puncture frequency and cerebrospinal fluid analysis in the neonate.
AB  - A prospective study was performed to assess the frequency and diagnostic utility
      of lumbar punctures in neonates both during their first week of life and
      thereafter. During the two 6-month periods from January 1, 1985 to June 30, 1985,
      and February 1, 1986 to July 31, 1986, 712 neonates underwent 728 lumbar
      punctures during their first week of life primarily as part of the evaluation for
      suspected infection, either congenital or postnatal. There were eight patients
      with positive spinal fluid cultures in the first week of life, but only one
      patient simultaneously had a positive blood culture and a clinical course
      consistent with meningitis. In contrast, a considerably higher yield,
      approximating five times that of the first week of life, was obtained in patients
      undergoing a lumbar puncture after the first week of life.

PMID- 1985431
TI  - Family history fails to identify many children with severe hypercholesterolemia.
AB  - Optimal strategies for identifying children with hypercholesterolemia have not
      been established. Several groups have advocated that testing of serum cholesterol
      levels be limited to those children who have family histories of hyperlipidemia
      or premature coronary heart disease. We studied the ability of comprehensive
      family histories to identify children with hyperlipidemia in a group of 114
      children (mean age, 8 +/- 4 years) who were referred for treatment of
      hypercholesterolemia. A positive family history was defined according to
      guidelines of the American Academy of Pediatrics. The mean fasting total
      cholesterol in the children was 5.74 +/- 1.42 mmol/L (222 mg/dL). Family history
      was negative for hypercholesterolemia or premature coronary heart disease in 22
      (22%) of 100 children with total cholesterol levels greater than the 75th
      percentile for their ages, in 13 (18.3%) of 71 children with total cholesterol
      levels greater than the 95th percentile for their ages, and in four (11.8%) of 34
      children with presumed heterozygous familial hypercholesterolemia. Of the 78
      children who had both hypercholesterolemia and positive family histories,
      hyperlipidemia was reported in 72 families, whereas premature heart disease was
      reported in only 27. We conclude that in a population of children referred
      because of known hypercholesterolemia, a detailed family history not only fails
      to identify many children with mild hypercholesterolemia, but also fails to
      identify a significant proportion of children with markedly elevated cholesterol
      levels. Additionally, in families of children with hypercholesterolemia, a
      history of hyperlipidemia is more common than a history of premature heart
      disease.

PMID- 1985432
TI  - Acute osteomyelitis in children. Reassessment of etiologic agents and their
      clinical characteristics.
AB  - One hundred thirty-five children with acute osteomyelitis were identified by
      chart review during a 7-year period, January 1, 1980, through December 31, 1986.
      Bacteriologic causes were detected in 75 (55%) of the patients. Staphylococcus
      aureus, Haemophilus influenzae type b, and Pseudomonas aeruginosa were identified
      in 34 (25%), 16 (12%), and eight (6%) children, respectively. Staphylococcus
      aureus occurred in all age groups, H influenzae type b occurred only in children
      younger than 3 years and was the number one cause of disease in this group.
      Pseudomonas aeruginosa occurred exclusively in children older than 9 years.
      Children with H influenzae type b had clinical and laboratory findings that were
      almost indistinguishable from a matched group of children with osteomyelitis due
      to other known bacteria, although children with H influenzae type b tended to
      have more joint effusions (63% vs 27%), less lower extremity disease (22% vs
      70%), and fewer positive cultures from bone or joint aspirates (41% vs 89%).
      Unlike most pediatric cases of osteomyelitis, the ones due to P aeruginosa did
      not represent the hematogenous route of infection; penetrating injury to the foot
      was present in every case. Children with P aeruginosa infections were older than
      9 years (100%), predominantly male (88%), often afebrile (83%), and never
      bacteremic. These data provide guidelines for the initial work-up and management
      of osteomyelitis in children.

PMID- 1985433
TI  - Pneumococcal osteomyelitis and arthritis in children. A hospital series and
      literature review.
AB  - Twenty-nine children with pneumococcal osteomyelitis and/or arthritis, 11 of whom
      had osteomyelitis, were treated at Cook County Hospital, Chicago, Ill, in the
      past 20 years. They were mostly normal children with a single focus of infection.
      They represented more than 5% of the hospitalized children with a systemic
      pneumococcal infection. Most of the pneumococcal isolates were serotyped;
      serotype 19, in particular, seemed to be unusually common in these children.
      Twenty-three of the 29 children with pneumococcal osteomyelitis and/or arthritis
      had been hospitalized in the past 15 years. These 23 children were compared with
      161 hospitalized children who had bone and joint infections with other isolated
      bacteria. The children with pneumococcal osteomyelitis and/or arthritis were
      indistinguishable from most of the other children, except by age. All but three
      of the children with pneumococcal osteomyelitis and/or arthritis were between the
      ages of 3 and 24 months. In this age group, Pneumococcus was the common isolate
      from children with osteomyelitis, and second only to Haemophilus influenzae from
      children with bacterial arthritis. Pneumococcal osteomyelitis and/or arthritis
      has never been rare; the medical literature describes at least 245 other
      children, most of whom were younger than 2 years.

PMID- 1985434
TI  - Influence of otitis media on the correlation between rectal and auditory canal
      temperatures.
AB  - In a noninterventional, controlled, single-blinded trial, 251 children were
      examined in a university hospital emergency department setting to study the
      influence of acute otitis media on the relationship between rectal and auditory
      canal temperatures. Bilateral auditory canal temperatures were measured using an
      infrared detection probe and microprocessor by nursing staff blinded to the
      presence of acute otitis media. Correlation between rectal and auditory canal
      temperatures in children with (r = .81) and without (r = .75) acute otitis media
      were not significantly different. There was no significant difference between
      infected (38.1 degrees C +/- 1.0 degree C) and uninfected ears (38.0 degrees C +/
      1.0 degree C) with unilateral otitis (n = 75). Although significantly higher
      than in uninfected children, auditory canal temperatures of children with acute
      otitis media reflected elevated rectal temperatures and not differences in
      auditory canal temperatures between ears.

PMID- 1985435
TI  - School health training during pediatric residency.
AB  - Pediatricians are becoming increasingly concerned about reaching beyond the
      office or clinic to help solve problems of child and family health. The
      physician's ability to interact with school personnel and communities is one
      important approach to this outreach effort. School health training has been a
      required 6-month component of the pediatric residency curriculum at the
      University of Texas Medical Branch, Galveston, since 1979, with second-year
      residents providing weekly on-site consultations to public school districts and
      participating in a weekly school health seminar series. In this study, graduates
      from this program were surveyed to determine their evaluations of the training
      and extent of current school involvement and to use their evaluations for
      curriculum evaluation. Residents who participated in the school consultation from
      1979 through 1988 were surveyed. Seventy-eight pediatricians responded, a 79%
      return rate. Ratings by the graduates reveal that both pediatric generalists and
      subspecialists highly value their training experiences. Ratings were not related
      to the specific site to which the resident consultant had been assigned. Of these
      pediatricians, 41% are currently consulting with school personnel. These findings
      are discussed as they relate to other reports of physician involvement in schools
      and provide clues to curriculum design for school health training in pediatric
      residency.

PMID- 1985436
TI  - Nevus flammeus. Discordance in monozygotic twins.
AB  - Nevus flammeus has been described as an inherited vascular anomaly. We report two
      cases of nevus flammeus, each appearing in one of two monozygotic twins. This
      finding supports the idea that nevus flammeus results from embryologic mishap
      rather than genetic transmission.

PMID- 1985437
TI  - Neural arch stenosis and spinal cord injury in thanatophoric dysplasia.
AB  - Bony abnormalities caused by thanatophoric dysplasia affect the base of the skull
      and the vertebrae as well as the ribs and appendicular long bones. We present our
      findings in a full-term infant with thanatophoric dysplasia in whom the posterior
      fossa, the rostral vertebral column, and the neuraxis at and adjoining the
      craniovertebral junction were studied by dissection, roentgenography, and
      histologic examination. In this infant, malformations of the vertebral laminae,
      most prominent in the basiocciput and atlas vertebra, led to compression of the
      rostral cervical spinal cord, causing gliosis and focal necrosis. Stenosis of the
      foramen magnum and spinal canal may contribute to the ventilatory insufficiency
      that often causes death in patients with thanatophoric dysplasia. We suggest that
      the causes of death in patients with thanatophoric dysplasia and other severe
      forms of osteochondrodysplasia should be sought in neuraxial injury rather than
      attributed solely to pulmonary hypoplasia.

PMID- 1985438
TI  - Marfanoid children. Etiologic heterogeneity and cardiac findings.
AB  - The clinical, cardiac, and echocardiographic test results of 20 children with
      marfanoid features are reviewed. Fifteen were diagnosed as having Marfan
      syndrome, two had "possible" Marfan syndrome, and three had other diagnoses. On
      first evaluation, eight patients with Marfan syndrome (53%) had mitral
      regurgitation and none had aortic regurgitation. Echocardiography showed aortic
      root enlargement in 12 (80%) of 15 patients and mitral valve prolapse in 12 (80%)
      of 15. None had a normal echocardiogram. At follow-up examination, one patient
      had developed aortic root enlargement, and one patient, mitral valve prolapse.
      Thus, although aortic root enlargement is usually present in early childhood in
      patients with Marfan syndrome, it is not considered specific because in this
      study it also occurred in one child with Alport's syndrome and in one with
      marfanoid features. Four patients with aortic root enlargement were treated with
      propranolol and their echocardiograms showed no further increase in the aortic
      root diameter for several years. We recommend echocardiography in the diagnosis
      and routine management of children in whom Marfan syndrome is suspected.

PMID- 1985439
TI  - Differences in expression of cystic fibrosis in blacks and whites.
AB  - The recent identification of the cystic fibrosis (CF) gene confirms that genetic
      heterogeneity occurs in CF. A three-base-pair deletion in exon 10 resulting in a
      loss of the phenylalanine residue at amino acid position 508 of the gene product,
      termed the CF conductance regulator protein, accounts for 70% of cases of CF in
      white subjects. However, this gene defect occurs in only 37% of affected blacks.
      Analysis of CF genes from American blacks has revealed a number of mutations,
      most of which are unique to that population. We therefore searched for potential
      differences in expression of CF between 24 black and 48 white patients with CF
      matched for birth date and gender. Black patients more frequently presented with
      only respiratory symptoms (38% vs 10%). Black patients had fewer hospitalizations
      for pulmonary exacerbations (2 vs 6.9), a better mean forced vital capacity (77%
      vs 62% of predicted), and higher chest roentgenogram scores (18.2 vs 14.4) than
      white patients. Complication rates were similar except for a higher incidence of
      hyponatremic dehydration (21% vs 2%) and peptic ulcer disease (13% vs 0%) in
      blacks. Survival time appeared to be longer in blacks, but the difference was not
      statistically significant. We conclude that phenotypic differences exist between
      black and white patients with CF, which may be due to the genetic heterogeneity
      between these two populations.

PMID- 1985440
TI  - Associations are not effects.

PMID- 1985441
TI  - Lifetime occupational physical activity and prostate cancer risk.
AB  - The authors compared the lifetime occupational physical activity of 452 prostate
      cancer cases identified through the population-based Hawaii Tumor Registry and
      899 population controls interviewed from 1981 to 1983. Each job reported was
      classified into one of five levels of physical activity using published sources.
      Among men aged 70 years or older, a negative association was found between
      prostate cancer risk and proportion of life spent in jobs involving only
      sedentary or light work. Compared with men never employed in such jobs, men who
      spent more than 54% of their life in these jobs had an odds ratio of 0.5 (95%
      confidence interval 0.3-0.9). This negative association was dose-dependent,
      consistent across ethnic groups, and unrelated to socioeconomic status, dietary
      risk factors, or job-related chemical exposures. The findings for younger men
      were less clear, but not inconsistent with those for older men. Surprisingly, no
      association was found with years spent in moderately active or very active jobs
      in either age group. Although inconclusive, these results suggest that physical
      activity may be positively associated with the risk of prostate cancer, but this
      association is likely to be weak and indirect.

PMID- 1985442
TI  - Hostility and coronary artery disease.
AB  - Studies of the association between type A behavior and coronary heart disease
      have yielded inconsistent findings. A possible explanation for these inconsistent
      findings is that type A behavior is simply a marker for other behaviors that are
      truly related to coronary heart disease. Hostility is one such behavior that has
      been found in several recent studies to predict coronary heart disease and
      coronary atherosclerosis; however, several other studies have found null results.
      In the present study, the predictive power of hostility was tested in a study
      population of hospitalized men (n = 118) and women (n = 40) scheduled for
      coronary angiography. Potential coronary risk behaviors were assessed in the
      angiography patients and they were given the type A Structured Interview.
      Hostility was measured with the Cook-Medley Hostility Inventory and the Behavior
      Pattern Hostility Index, a measure of hostility derived from the type A
      Structured Interview. No significant positive associations were found for either
      Cook-Medley hostility or behavior pattern hostility and coronary occlusion. This
      was true whether hostility or coronary occlusion was treated as a dichotomous
      variable or as a continuous variable. In fact, most of the observed associations
      were opposite to the predicted direction, although none was statistically
      significant. Replicating cutpoints of the Cook-Medley Hostility Inventory used in
      other studies that have reported positive associations with coronary heart
      disease also yielded null findings. The association between hostility and
      coronary occlusion was slightly modified by age and sex, but the interaction
      coefficients were not significant. The sample size yielded adequate statistical
      power to detect the hypothesized associations, and there was no evidence that
      selection bias, measurement error, or unexamined confounding accounted for the
      null findings. These results failed to confirm some earlier reports showing a
      positive association between hostility and coronary artery disease.

PMID- 1985443
TI  - Comparison of infant mortality among twins and singletons: United States 1960 and
      1983.
AB  - Infant mortality among US black and white twins and singletons was compared for
      1960 and 1983 using the Linked Birth/Infant Death Data Sets from the National
      Center for Health Statistics. Both twin and singleton infant mortality rates
      showed impressive declines since 1960 but almost all of the improvement in
      survival for both twins and singletons was related to increased birth weight
      specific survival rather than improved birth weight distribution. One-half of
      white twins and two-thirds of black twins weighed less than 2,500 g at birth, and
      9% of white twin births and 16% of black twin births were in the very low (less
      than 1,500g) birth weight category. In 1983, twin infant mortality rates were
      still four to five times that of singletons. However, twins had a survival
      advantage in the 1,250-3,000 g range, which persisted after adjustment for
      gestational age. Cause-specific mortality among twins was considerably higher for
      every major cause of death: twin mortality risks due to newborn respiratory
      disease, maternal causes, neonatal hemorrhage, and short gestation/low birth
      weight were six to 15 times that of singletons. The lowest twin-to-singleton
      mortality ratios observed were for congenital anomalies and sudden infant death
      syndrome with relative risks twice that of singletons. The data underscore the
      need to develop effective strategies to decrease infant mortality among twins.

PMID- 1985444
TI  - The case-crossover design: a method for studying transient effects on the risk of
      acute events.
AB  - A case-control design involving only cases may be used when brief exposure causes
      a transient change in risk of a rare acute-onset disease. The design resembles a
      retrospective nonrandomized crossover study but differs in having only a sample
      of the base population-time. The average incidence rate ratio for a hypothesized
      effect period following the exposure is estimable using the Mantel-Haenszel
      estimator. The duration of the effect period is assumed to be that which
      maximizes the rate ratio estimate. Self-matching of cases eliminates the threat
      of control-selection bias and increases efficiency. Pilot data from a study of
      myocardial infarction onset illustrate the control of within-individual
      confounding due to temporal association of exposures.

PMID- 1985445
TI  - Group day care and the risk of serious infectious illnesses.
AB  - Group day care attendance has been associated with an increased risk of
      infectious illnesses. With the exception of illnesses caused by Haemophilus
      influenzae type b (H. influenzae) and Neisseria Meningitidis (N. meningitidis),
      most studies have examined relatively mild illnesses. A matched case-control
      study was conducted to study the association between group day care attendance
      and serious infectious illnesses (requiring hospitalization). Cases were children
      aged 3 months to 59 months hospitalized for an infectious illness at Yale-New
      Haven Hospital from June 1984 through November 1986. Each case was matched to a
      control by date of birth and regular pediatrician, and their parents were
      interviewed. Data from 193 matched pairs were analyzed using conditional logistic
      regression. The matched odds ratio (OR) for the association between group day
      care attendance and serious infectious illness was 1.39 (95% confidence interval
      (CI) 0.87-2.20). For pairs in which the case had an H. influenzae infection (n =
      46), the odds ratio was 8.00 (95% CI 1.00-63.85), and for N. meningitidis (n = 9)
      the odds ratio was 2.00 (95% CI 0.39-10.27). In the remaining 138 pairs, the odds
      ratio was 1.27 (95% CI 0.76-2.12). In infants less than 12 months of age (n = 64)
      the odds ratio for group day care and illnesses (excluding H. influenzae and N.
      meningitidis) was 1.66 (95% CI 0.73-3.80) and it was 1.06 (95% CI 0.55-2.05) for
      older children (n = 74). The data suggested an association between day care
      attendance and invasive bacterial infections other than H. influenza and N.
      meningitidis, OR = 2.00 (95% CI 0.81-4.94) but not for local bacterial
      infections, OR = 1.00 (95% CI 0.25-4.00) or infections of presumed viral
      etiology, OR = 1.00 (95% CI 0.49-2.05). Important predictors of serious
      infections (excluding H. influenzae and N. meningitidis) were passive smoking (OR
      = 3.96, 95% CI 2.16-7.24) and sharing a bedroom (OR = 2.31, 95% CI 1.23-4.33).
      These findings do not suggest that group day care attendance poses a large risk
      of serious infections (other than H. influenzae or N. meningitidis) to young
      children; however, at least one preventable factor, passive smoking, may.

PMID- 1985446
TI  - Assessment of the protective value of antibodies to the Plasmodium falciparum
      ring-infected erythrocyte surface antigen (RESA): an epidemiologic study in
      Madagascar.
AB  - The ring-infected erythrocyte surface antigen (RESA), a Plasmodium falciparum
      merozoite antigen, is a major vaccine candidate against falciparum malaria. To
      investigate the protective role of antibodies to RESA and its 4-mer, 8-mer, and
      11-mer repeated amino acid sequences under conditions of natural exposure, a case
      control and a cohort study were carried out in 1988 in a rural community in
      Madagascar where malaria reappeared recently. Fifty cases with greater than 1,000
      P. falciparum per microliter of blood, and 45 controls with a negative blood
      smear were enrolled and sera were collected. Forty-one controls were followed for
      20 weeks to identify malarial attacks. Protection against clinical malaria was
      assessed by the absence of malarial attacks requiring therapy. At enrollment,
      positivity rates and reactivity levels to RESA or repeats were similar in cases
      and controls. The 11-mer repeat antibody level was higher in the 26 controls who
      experienced at least one malarial attack during follow-up than in the 15 other
      controls (p less than 0.01). Thus, antibodies to the 11-mer repeat were
      predictors of the subsequent appearance of the disease. After adjustment for
      antibodies to the 11-mer repeat, antibodies to whole RESA had a negative
      predictive value on the occurrence of malarial attacks (p = 0.04). Different
      epitopes within the RESA molecule may elicit production of antibodies with
      different activities.

PMID- 1985447
TI  - Underlying and proximate determinants of child health: the Cebu Longitudinal
      Health and Nutrition Study.
AB  - A proper understanding of infant health requires the integration of
      socioeconomic, behavioral, and biomedical models. A methodology is presented for
      assessing the effects of "underlying" social factors and "proximate" behavioral
      and biomedical factors on infant morbidity, growth, and mortality. The method is
      applied to data collected from over 3,000 children in Cebu, Philippines, over the
      first 2 years of life. Data were collected between 1983 and 1985. A central theme
      is that mothers recognize certain observable and nonobservable threats to the
      health of their infants, and that the mothers take measures to reduce the risk
      from such threats. It is shown that if conventional statistical techniques (which
      do not take such behaviors into account) are used, the estimates of the effect of
      the risk factors on health are incorrect. Procedures for obtaining correct
      estimates are described. The application of the methodology is illustrated by
      modeling childhood diarrhea, and by showing how maternal education induces
      behavioral changes, and how these changes, in turn, induce changes in the
      prevalence of childhood diarrhea.

PMID- 1985448
TI  - Breast cancer, cigarette smoking, and passive smoking.

PMID- 1985449
TI  - Re: "Wartime determinants of arteriographically confirmed coronary artery disease
      in Beirut".

PMID- 1985450
TI  - Re: "A simple method to calculate the confidence interval of a standardized
      mortality ratio (SMR)".

PMID- 1985452
TI  - A mutant allele common to the type I adenine phosphoribosyltransferase deficiency
      in Japanese subjects.
AB  - Adenine phosphoribosyltransferase (APRT) deficiency is a genetic disorder which
      causes 2,8-dihydroxy-adenine urolithiasis. The estimated incidence of
      heterozygosity in Caucasian and Japanese populations is 1%. Mutant alleles
      responsible for the disease have been classified as APRT*Q0 (type I) and APRT*
      (type II). In our previous study, we demonstrated in APRT*J a single common base
      change which accounts for 70% of the Japanese mutants. The present report
      describes the analysis of an APRT*Q0 mutation in Japanese subjects. Two
      nucleotide substitutions common to all seven affected alleles from four unrelated
      subjects (three homozygotes and a heterozygote) were identified: G----A at
      nucleotide position 1453 and C----T at 1456. The G----A altered the amino acid
      Trp98 to a stop codon. The C----T did not alter Ala99. These point mutations were
      demonstrated by sequence analysis of polymerase chain reaction (PCR)-amplified
      genomic DNA and cDNA. The G----A change at 1453 results in the elimination of a
      PflMI site in the APRT gene. PflMI digests, which were used to confirm the G----A
      transition, can be useful in screening for this specific mutation.

PMID- 1985451
TI  - Mapping of human chromosome Xq28 by two-color fluorescence in situ hybridization
      of DNA sequences to interphase cell nuclei.
AB  - We have used the proximity of probe hybridization sites in interphase chromatin
      to derive the order of DNA sequences in a 2-3-Mbp region of human chromosome
      Xq28. The map generated bridges the results of genetic and pulsed-field gel
      electrophoresis mapping to produce a more complete map of Xq28 than possible with
      either of these other techniques alone. Two-color fluorescence in situ
      hybridization (FISH) was used to detect the positions of two or more probes in G1
      male interphase nuclei. We show that cosmids that are 50 kbp to 2-3 Mbp apart can
      be ordered rapidly with two alternative approaches: (1) by comparing the average
      measured distance between two probes and (2) simply by scoring the order of red
      and green fluorescent dots after detection of three or more probes with two
      fluorochromes. The validity of these approaches is demonstrated using five
      cosmids from a region spanning approximately 800 kbp that includes the factor
      VIII (F8), glucose-6-phosphate dehydrogenase (G6PD), and color-vision pigment
      (CV) genes. The cosmid map derived from interphase mapping is consistent with the
      map determined by restriction-fragment analysis. The two interphase mapping
      approaches were then used (1) to orient the F8/CV cluster relative to two
      markers, c1A1 and st14c, which we show by metaphase mapping to be proximal to the
      F8/CV cluster, (2) to position st14c (DXS52) between c1A1 and F8, and (3) to
      orient the CV gene cluster relative to G6PD by using two CV-flanking cosmids,
      18b41 and fr7. The probe order in Xq28 derived from interphase proximity is cen
      c1A1-st14c-5'F8 (p624-p542-p625)-G6PD-18b41-3' green-green-red-fr7-tel. We also
      show that, to determine their order by using metaphase chromosomes, sequences
      must be at least 1 Mbp apart, an order of magnitude greater than required in
      interphase chromatin. The data show that FISH mapping is a simple way to order
      sequences separated by greater than or equal to 50 kbp for the construction of
      long-range maps of mammalian genomes.

PMID- 1985453
TI  - Fitting mixture distributions to phenylthiocarbamide (PTC) sensitivity.
AB  - A technique for fitting mixture distributions to phenylthiocarbamide (PTC)
      sensitivity is described. Under the assumptions of Hardy-Weinberg equilibrium, a
      mixture of three normal components is postulated for the observed distribution,
      with the mixing parameters corresponding to the proportions of the three
      genotypes associated with two alleles A and a acting at a single locus. The
      corresponding genotypes AA, Aa, and aa are then considered to have separate means
      and variances. This paper is concerned with estimating the parameters of the
      model, and their standard errors, by using an application of the EM algorithm.
      This technique also caters for the fact that the sensitivity measurements are
      only known to lie between the endpoints of certain intervals and that the exact
      measurement of the attribute is not possible.

PMID- 1985455
TI  - Mothers' postcounseling beliefs about the causes of their children's genetic
      disorders.
AB  - Mothers' postcounseling beliefs about the causes of their children's genetic
      disorders were investigated by means of a Q-sort consisting of 54 statements of
      possible beliefs that were sorted into nine groups of six items each on the basis
      of congruence with the subject's beliefs. The subjects were well educated,
      knowledgeable about the genetics of their child's disorder, and indicated a high
      level of belief in genetic causes. Differences in beliefs were associated with
      differences in genetic etiology, indicating that beliefs were affected by the
      specific information provided in genetic counseling. Factor analysis identified a
      cluster of Q-sort items characterized by a highly personal relationship to the
      cause of the disorder (e.g., personal attributes, being selected and blessed, and
      God's actions). Subjects who rated these items low had a belief pattern,
      designated impersonal, that was consistent with a scientific worldview and that
      indicated psychological distancing from the cause of the child's disorder.
      Subjects who rated these items high, the personal belief pattern, had a mixture
      of scientific and nonscientific beliefs that indicated a sense of personal
      involvement in the cause of the child's disorder. Subjects with the two belief
      patterns were equally knowledgeable about the genetics of the disorder. Thus, the
      personal belief pattern did not appear to interfere with acceptance or
      understanding of the information provided in genetic counseling.

PMID- 1985456
TI  - A family study of Gilles de la Tourette syndrome.
AB  - Previous studies have demonstrated that Gilles de la Tourette syndrome (TS) is a
      familial disorder and that chronic tics (CT) and obsessive compulsive disorder
      (OCD) appear to be etiologically related to the syndrome. In the present study we
      report the results from a study of 338 biological relatives of 86 TS probands, 21
      biologically unrelated relatives of adopted TS probands, and 22 relatives of
      normal subjects. The 43 first-degree relatives of the adopted TS and normal
      probands constituted a control sample. The rates of TS, CT, and OCD in the total
      sample of biological relatives of TS probands were significantly greater than in
      the relatives of controls. In addition, the morbid risks of TS, OCD, and CT were
      not significantly different in families of probands with OCD when compared to
      relatives of probands without OCD. These findings provide further evidence that
      OCD is etiologically related to TS.

PMID- 1985454
TI  - Identification of a highly polymorphic microsatellite VNTR within the
      argininosuccinate synthetase locus: exclusion of the dystonia gene on 9q32-34 as
      the cause of dopa-responsive dystonia in a large kindred.
AB  - Dopa-responsive dystonia is a clinical variant of idiopathic torsion dystonia
      that is distinguished from other forms of dystonia by the frequent occurrence of
      parkinsonism, diurnal fluctuation of symptoms, and its dramatic therapeutic
      response to L-dopa. Linkage of a gene causing classic dystonia in a large non
      Jewish kindred (DYT1) and in a group of Ashkenazi Jewish families, to the
      gelsolin (GSN) and arginino-succinate synthetase (ASS) loci on chromosome 9q32
      34, respectively, was recently determined. Here we report the discovery of a
      highly informative (GT)n repeat VNTR polymorphism within the ASS locus. Analysis
      of a large kindred with dopa-responsive dystonia, using this new polymorphism and
      conventional RFLPs for the 9q32-34 region, excludes loci in this region as a
      cause of this form of dystonia. This provides proof of genetic heterogeneity
      between classic idiopathic torsion dystonia and dopa-responsive dystonia.

PMID- 1985457
TI  - Chromosome 15 uniparental disomy is not frequent in Angelman syndrome.
AB  - Genetic imprinting has been implicated in the etiology of two clinically distinct
      but cytogenetically indistinguishable disorders--Angelman syndrome (AS) and
      Prader-Willi syndrome (PWS). This hypothesis is derived from two lines of
      evidence. First, while the molecular extents of de novo cytogenetic deletions of
      chromosome 15q11q13 in AS and PWS patients are the same, the deletions originate
      from different parental chromosomes. In AS, the deletion occurs in the maternally
      inherited chromosome 15, while in PWS the deletion is found in the paternally
      inherited chromosome 15. The second line of evidence comes from the deletion of
      an abnormal parental contribution of 15q11q13 in PWS patients without a
      cytogenetic and molecular deletion. These patients have two maternal copies and
      no paternal copy of 15q11q13 (maternal uniparental disomy) instead of one copy
      from each parent. By qualitative hybridization with chromosome 15q11q13 specific
      DNA markers, we have now examined DNA samples from 10 AS patients (at least seven
      of which are familial cases) with no cytogenetic or molecular deletion of
      chromosome 15q11q13. Inheritance of one maternal copy and one paternal copy of
      15q11q13 was observed in each family, suggesting that paternal uniparental disomy
      of 15q11q13 is not responsible for expression of the AS phenotype in these
      patients.

PMID- 1985458
TI  - On the inheritance of abdominal aortic aneurysm.
AB  - To determine the mode of inheritance of abdominal aortic aneurysm, data on first
      degree relatives of 91 probands were collected. Results of segregation analysis
      performed on these data are reported. Many models, including nongenetic and
      genetic models, were compared using likelihood methods. The nongenetic model was
      rejected; statistically significant evidence in favor of a genetic model was
      found. Among the many genetic models compared, the most parsimonious genetic
      model was that susceptibility to abdominal aortic aneurysm is determined by a
      recessive gene at an autosomal diallelic major locus. A multifactorial component
      in addition to the major locus does not increase the likelihood of the data
      significantly.

PMID- 1985459
TI  - Allele frequency estimation from data on relatives.
AB  - Given genetic marker data on unrelated individuals, maximum-likelihood allele
      frequency estimates and their standard errors are easily calculated from sample
      proportions. When marker phenotypes are observed on relatives, this method cannot
      be used without either discarding a subset of the data or incorrectly assuming
      that all individuals are unrelated. Here, I describe a method for allele
      frequency estimation for data on relatives that is based on standard methods of
      pedigree analysis. This method makes use of all available marker information
      while correctly taking into account the dependence between relatives. I
      illustrate use of the method with family data for a VNTR polymorphism near the
      apolipoprotein B locus.

PMID- 1985460
TI  - A 3-bp deletion in the rhodopsin gene in a family with autosomal dominant
      retinitis pigmentosa.
AB  - Autosomal dominant retinitis pigmentosa (ADRP) has recently been linked to locus
      D3S47 (probe C17), with no recombination, in a single large Irish family. Other
      ADRP pedigrees have shown linkage at zero recombination, linkage with
      recombination, and no linkage, demonstrating genetic heterogeneity. The gene
      encoding rhodopsin, the rod photoreceptor pigment, is closely linked to locus
      D3S47 on chromosome 3q. A point mutation changing a conserved proline to
      histidine in the 23d codon of the gene has been demonstrated in affected members
      of one ADRP family and in 17 of 148 unrelated ADRP patients. We have sequenced
      the rhodopsin gene in a C17-linked ADRP family and have identified in the 4th
      exon and in-frame 3-bp deletion which deletes one of the two isoleucine monomers
      at codons 255 and 256. This mutation was not found in 30 other unrelated ADRP
      families. The deletion has arisen in the sequence TCATCATCAT, deleting one of a
      run of three x 3-bp repeats. The mechanism by which this occurred may be similar
      to that which creates length variation in so-called mini- and microsatellites.
      Thus ADRP is an extremely heterogeneous disorder which can result from a range of
      defects in rhodopsin and which can have a locus or loci elsewhere in the genome.

PMID- 1985461
TI  - Localization of the Aland Island eye disease locus to the pericentromeric region
      of the X chromosome by linkage analysis.
AB  - Aland Island eye disease (AIED) is an X-chromosomal disorder characterized by
      reduced visual acuity, progressive axial myopia, regular astigmatism, latent
      nystagmus, foveal hypoplasia, defective dark adaptation, and fundus
      hypopigmentation. The syndrome was originally reported in 1964 in a family on the
      Aland Islands. To determine the localization of the AIED gene, linkage studies
      were performed in this family. total of 37 polymorphisms, covering loci on the
      entire X chromosome, were used. By two-point analysis the strongest evidence for
      linkage was obtained between AIED and DXS255 (maximum lod score [Zmax] 4.92 at
      maximum recombination fraction [theta max] .00). Marker loci DXS106, DXS159, and
      DXS1 also showed no recombination with AIED. Other positive lod scores at theta
      max .00 were obtained with markers localized in the XY homologous region in Xq13
      q21, but the numbers of informative meioses were small. Multilocus linkage
      analysis indicated that the most probable location of AIED is in the
      pericentromeric region between DXS7 and DXS72. These results rule out
      localizations of AIED more distal on Xp that have been proposed by others. Our
      data do not exclude the possibility that AIED and incomplete congenital
      stationary night blindness are caused by mutations in the same gene. This
      question should be resolved by careful clinical comparison of the disorders and
      ultimately by the molecular dissection of the genes themselves.

PMID- 1985462
TI  - Pearson syndrome and mitochondrial encephalomyopathy in a patient with a deletion
      of mtDNA.
AB  - A patient is described who has features of Pearson syndrome and who presented in
      the neonatal period with a hypoplastic anemia. He later developed hepatic, renal,
      and exocrine pancreatic dysfunction. At the age of 5 years he developed visual
      impairment, tremor, ataxia, proximal muscle weakness, external ophthalmoplegia,
      and a pigmentary retinopathy (Kearns-Sayre syndrome). Muscle biopsy confirmed the
      diagnosis of mitochondrial myopathy. Analysis of mtDNA from leukocytes and muscle
      showed mtDNA heteroplasmy in both tissues, with one population of mtDNA deleted
      by 4.9 kb. The deleted region was bridged by a 13-nucleotide sequence occurring
      as a direct repeat in normal mtDNA. Both Pearson syndrome and Kearns-Sayre
      syndrome have been noted to be associated with deletions of mtDNA; they have not
      previously been described in the same patient. These observations indicate that
      the two disorders have the same molecular basis; the different phenotypes are
      probably determined by the initial proportion of deleted mtDNAs and modified by
      selection against them in different tissues.

PMID- 1985463
TI  - Localization of DNA sequences to a region within Xp11.21 between incontinentia
      pigmenti (IP1) X-chromosomal translocation breakpoints.
AB  - Incontinentia pigmenti (IP) is an X-linked dominant disorder characterized by
      developmental anomalies of the tissues and organs derived from embryonic ectoderm
      and neuroectoderm. An IP locus, designated IP1, probably resides in Xp11.21,
      since five unrelated patients with nonfamilial IP have been identified who
      possess constitutional de novo reciprocal X;autosome translocations involving
      Xp11.21. We have used a series of somatic cell hybrids containing the rearranged
      chromosomes derived from three of the five IP1 patients, along with other hybrid
      cell lines, to map probes in the vicinity of the IP1 locus. Five anonymous DNA
      loci--DXS422, DXS14, DXS343, DXS429, and DXS370--have been mapped to a region
      within Xp11.21, between two IP1 X-chromosomal translocation breakpoints; the IP1
      t(X;17) breakpoint is proximal (centromeric) to this region, and the IP1 t(X;13)
      and t(X;9) X-chromosomal breakpoints lie distal to it. While no IP1 translocation
      breakpoint has yet been identified by pulsed-field gel electrophoretic (PFGE)
      analysis, an overlap between three probes--p58-1, 7PSH3.5, and cpX210--has been
      detected, placing these probes within 125 kb. Four probes--p58-1, 7PSH3.5,
      cpX210, and 30CE2.8--have been helpful in constructing a 1,250-kb PFGE map of the
      region between the breakpoints; these results suggest that the IP1 X-chromosomal
      translocation breakpoints are separated by at least this distance. The combined
      somatic cell hybrid and PFGE analyses we report here favor the probe order DXS323
      (IP1 t(X;13), IP1, t(X;9]-(DXS422, DXS14, DXS343, DXS429, DXS370)-(IP1 t(X;17),
      DXZ1). These sequences provide a starting point for identifying overlapping
      genomic sequences that span the IP1 translocation breakpoints; the availability
      of IP1 translocation breakpoints should now assist the cloning of this locus.

PMID- 1985464
TI  - Immunochemical studies of ferrochelatase protein: characterization of the normal
      and mutant protein in bovine and human protoporphyria.
AB  - Protoporphyria is a hereditary disorder characterized by a marked decrease in the
      activity of ferrochelatase, the terminal enzyme in the heme biosynthetic pathway.
      We have prepared specific polyvalent antibodies against bovine ferrochelatase in
      rabbits. The specificity of the antibody preparation against ferrochelatase was
      demonstrated by western blot analysis and immunoprecipitation of ferrochelatase
      activity. The antibody also cross-reacted weakly with ferrochelatase from human
      mitochondria. To quantify immunoreactive ferrochelatase in tissue samples, a
      kinetic-based enzyme-linked immunosorbent assay (k-ELISA) was developed.
      Ferrochelatase activity and the level of immunoreactive protein were measured in
      hepatic mitochondria isolated from six normal and nine protoporphyric
      (homozygous) cattle. Ferrochelatase activity was less than 10% of normal in
      mitochondria from protoporphyric animals; the amount of immunoreactive material
      was equivalent to that from normal animals. Similar studies were performed with
      samples from three normal and two protoporphyric (heterozygous) humans.
      Ferrochelatase activity was decreased in protoporphyric samples (about 17% of
      normal, but there was no concomitant decrease in immunoreactive material. These
      data demonstrate that a normal amount of ferrochelatase protein is present and
      suggest that bovine and human protoporphyria result from point mutations in the
      gene encoding ferrochelatase.

PMID- 1985465
TI  - Distribution of deletions and seven point mutations on CYP21B genes in three
      clinical forms of steroid 21-hydroxylase deficiency.
AB  - To characterize mutations in the CYP21B gene that are responsible for congenital
      adrenal hyperplasia (CAH), DNA samples from 91 French patients have been studied
      by allelic-specific oligonucleotide hybridization and Southern blot analysis.
      Seven sites mostly found in the CYP21A pseudogene and deletions of the functional
      CYP21B gene have been screened. Gene conversions involving small DNA segments
      accounted for 57% of the tested mutations and probably cause 74% of the mutations
      responsible for the disease. Complete deletion of the CYP21B gene accounted for
      18% of the CAH mutations in the whole sample and for 21% in the classical form of
      the disease. Three mutations were found associated with specific clinical forms
      of the disease: a G-C substitution in the seventh exon was associated with the
      late-onset form of the disease, and both an 8-bp depletion in the third exon and
      complete deletion of CYP21B were associated with the salt-wasting form.

PMID- 1985466
TI  - 11th annual meeting of the Society of Perinatal Obstetricians. January 28
      February 2, 1991, San Francisco, California. Abstracts.

PMID- 1985467
TI  - Surgical removal of subfoveal neovascularization in the presumed ocular
      histoplasmosis syndrome.
AB  - We treated two patients with presumed ocular histoplasmosis, subfoveal
      neovascular membranes, and progressive visual acuity loss to 20/400.
      Vitreoretinal surgical techniques were used to remove the subfoveal membranes.
      Visual acuity returned to 20/20 with seven months of follow-up in one patient
      (Case 1) and to 20/40 with three months of follow-up in the other patient (Case
      2). No evidence of persistent or current subretinal neovascular membranes in
      either patient have been noted. These preliminary results suggest that
      vitreoretinal surgical techniques may be successful in mechanically removing
      subfoveal neovascular membranes with preservation of overlying neurosensory
      retina and thus preservation of central visual acuity.

PMID- 1985468
TI  - Hydroxyamphetamine. A good drug lost?

PMID- 1985469
TI  - Transesophageal echocardiography for detecting mitral valve prolapse with retinal
      artery occlusions.

PMID- 1985470
TI  - Use of transesophageal echocardiography for detection of a likely source of
      embolization to the central retinal artery.

PMID- 1985471
TI  - Follicular conjunctivitis associated with apraclonidine.

PMID- 1985472
TI  - The importance of the Schirmer test with nasal stimulation.

PMID- 1985473
TI  - Discoid lupus erythematosus of the eyelid complicated by wound dehiscence.

PMID- 1985474
TI  - Hepatic cirrhosis as a doubtful cause of eyelid retraction.

PMID- 1985475
TI  - Flotation devices to facilitate amblyopia therapy.

PMID- 1985476
TI  - Retinal pigment epitheliopathy in acute leukemia.

PMID- 1985477
TI  - Metastatic renal cell carcinoma of the iris manifesting as an intrastromal iris
      cyst.

PMID- 1985478
TI  - Meibomian gland carcinoma in a 20-year-old patient.

PMID- 1985479
TI  - A new instrument for use in evisceration.

PMID- 1985480
TI  - Flavobacterium meningosepticum keratitis successfully treated with topical
      trimethoprim-sulfamethoxazole.

PMID- 1985481
TI  - Pneumocystis carinii choroiditis after long-term aerosolized pentamidine therapy.

PMID- 1985482
TI  - The gradient filter test to assess amblyopia.

PMID- 1985483
TI  - Vitrectomy retinotomy aspiration biopsy of choroidal tumors.

PMID- 1985484
TI  - Causes of failure after repeat vitreoretinal surgery for recurrent proliferative
      vitreoretinopathy.
AB  - During the last two years, we performed vitreoretinal surgery on 37 eyes with
      retinal detachments and recurrent severe proliferative vitreoretinopathy in 37
      patients who had had previous failed scleral buckling and vitreous surgery for
      proliferative vitreoretinopathy. Anterior proliferative vitreoretinopathy was
      present in 32 of 37 eyes (86%); posterior proliferative vitreoretinopathy of
      fixed retinal folds in four quadrants of narrow or closed funnel shape occurred
      in 23 of 37 eyes (62%); and subretinal proliferation was noted in 16 of 37 eyes
      (43%). The retinas in 12 eyes (32%) redetached from new or recurrent anterior
      proliferative vitreoretinopathy in nine eyes, reopening of pre-existing retinal
      breaks in two eyes, or recurrent posterior periretinal proliferation in one eye.
      With additional vitreoretinal procedures in six eyes and after a mean follow-up
      period of 11 months, 27 of 37 retinas (73%) were totally reattached, and an
      additional five eyes (13%) had retinal reattachment posterior to the scleral
      buckle. Of the 32 patients with posterior retinal reattachment, final visual
      acuity of 5/200 or better was attained in 19 eyes (59%).

PMID- 1985485
TI  - Prevalence of lattice degeneration and its relation to axial length in severe
      myopia.
AB  - We studied 436 eyes of 218 patients with myopia of -6.00 diopters or more in both
      eyes. Of 218 patients, 72 (33.0%) had lattice degeneration of the retina. Among
      these 72 patients, lattice lesions were uniocular in 39 (54.2%) and binocular in
      33 (45.8%). Of 105 males, 33 (31.4%) had lattice degeneration; of 113 females, 39
      (34.5%) had lattice degeneration. Contrary to previously published data, we found
      an inverse relationship between axial length and the prevalence of lattice
      degeneration in severely myopic eyes. The greatest prevalence of lattice
      degeneration (63 of 154 eyes, 40.9%) was found in eyes with an axial length of
      26.0 to 26.9 mm (-6.00 to -8.70 diopters), and the least prevalence of lattice
      degeneration (five of 71 eyes, 7.0%) was found in eyes with an axial length of
      32.0 mm (-24.00 diopters) or greater. This may explain the observation that
      retinal detachment after cataract surgery has been noted more commonly among
      patients with moderate than severe myopia.

PMID- 1985486
TI  - Ocular clinicopathologic study of gyrate atrophy.
AB  - We performed a histopathologic study of whole globes obtained post mortem from a
      patient with well-documented, vitamin B6-responsive gyrate atrophy. The retina in
      the posterior pole had focal areas of photoreceptor atrophy with adjacent retinal
      pigment epithelial hyperplasia. An abrupt transition from the near normal retina
      to a zone of near total atrophy of the retina, retinal pigment epithelium, and
      choroid was present in the fundus midperiphery. Electron microscopic examination
      disclosed abnormalities of the mitochondria of the corneal endothelium and the
      non-pigmented ciliary epithelium. Similar, but less severe, mitochondrial
      abnormalities were present in the photoreceptors.

PMID- 1985488
TI  - Photic retinal injury from endoillumination during vitrectomy.
AB  - We treated a patient who developed a paramacular area of light-induced retinal
      damage after endoscopic epimacular membrane removal. Postoperative color
      photographs showed complete absence of the membrane, but fluorescein angiography
      demonstrated a previously absent superior paramacular lesion consistent with a
      photic injury. Operative microscope illumination had been eliminated by corneal
      shielding, which implicated endoillumination as the source of injury. We
      recommend the following procedures to avoid this complication: careful planning
      of vitreous surgery for epimacular membrane removal; using filters; minimizing
      the length of surgery; keeping the light output low; maintaining maximal light
      pipe distance from the retina; eccentric orientation of the light pipe; and use
      of intermittent and variable site illumination techniques.

PMID- 1985487
TI  - Signs, complications, and platelet aggregation in familial exudative
      vitreoretinopathy.
AB  - Between 1979 and 1989, I examined 106 patients (16 pedigrees) with signs of
      familial exudative vitreoretinopathy. Of these patients, 101 had familial
      exudative vitreoretinopathy, and five had a sporadic manifestation. The
      complications of familial exudative vitreoretinopathy, deformation of the
      posterior retina, vitreous hemorrhage, amblyopia, and retinal detachment, caused
      diminished visual acuity. Of 170 eyes, retinal neovascularization was observed in
      18 eyes (11%), and retinal exudates were observed in 16 eyes (9%). Several forms
      of retinal detachment occurred in 37 of 180 eyes (21%), which often took an
      unfavorable course. A falciform retinal fold was observed in 14 eyes (8%).
      Retinal surgery was performed in 14 eyes; reattachment of the retina was
      successful in only seven eyes. Platelet aggregation studies disclosed no
      significant differences between seven patients with familial exudative
      vitreoretinopathy and ten control subjects. The pathogenesis of the disease is
      based on a premature arrest of the vascular development of the retina.

PMID- 1985489
TI  - Light damage in detached retina.
AB  - We injected homologous fibroblasts over the retinal vascular wing in five rabbits
      to induce a tractional retinal detachment. Eleven days later, a focal area of
      detachment was exposed to 30 minutes of visible light by an intraocular
      fiberoptic probe. Histologic damage to the detached retina exposed to light was
      demonstrated. The outer retina was affected most severely.

PMID- 1985490
TI  - Correlation between intraocular pressure control and progressive glaucomatous
      damage in primary open-angle glaucoma.
AB  - Fifty-five patients with primary open-angle glaucoma and early glaucomatous
      damage who had medical therapy and laser trabeculoplasty were followed up for
      four to 11 years or until progressive glaucomatous damage was documented. Factors
      associated with the stability or progression of glaucoma were evaluated. Eyes
      with mean intraocular pressure higher than 21 mm Hg during the follow-up period
      uniformly had progressive glaucomatous changes. Conversely, eyes with mean
      intraocular pressure less than 17 mm Hg remained stable, and approximately half
      of the eyes with mean intraocular pressure between 17 and 21 mm Hg had
      progressive glaucomatous changes. Patients who remained stable were slightly
      younger than those with progressive glaucomatous changes (P less than .05), but
      initial optic nerve head appearance, initial visual field findings, number of
      medicines used, medical history, and patient gender or race were not
      statistically associated with stability or progression of the glaucoma. These
      findings reinforce the importance of intraocular pressure control in primary open
      angle glaucoma and the need to identify other markers that help determine the
      proper level of intraocular pressure for individual patients.

PMID- 1985491
TI  - Increased intraocular pressure in severely burned patients.
AB  - Six eyes of three patients with severe body burns had intraocular pressure
      ranging from 37.2 to 81.7 mm Hg. Because of extreme orbital congestion, lateral
      canthotomies were performed, which caused abrupt decrease in intraocular pressure
      (range, 17.6 to 49.0 mm Hg). None of the patients had a history of glaucoma,
      narrow angles, or any precondition for a pupillary block mechanism. Two patients
      survived and neither had optic nerve damage or increased intraocular pressure
      after hospital discharge. Tonometry should be performed in patients with severe
      burns and orbital congestion, especially in those patients receiving large
      amounts of intravenous fluids. Lateral canthotomies may be of benefit to relieve
      potentially damaging high intraocular pressure.

PMID- 1985492
TI  - The effect of Perkins, Tono-Pen, and Schiotz tonometry on intraocular pressure.
AB  - We studied the intraocular pressure changes produced in five eye bank eyes by
      Perkins, Tono-Pen, and Schiotz tonometry performed by experienced and
      inexperienced personnel. When all users were considered together, Perkins
      tonometry produced a mean intraocular pressure increase of 0.7 mm Hg,
      significantly less than the mean increase of 12.1 mm Hg produced by Tono-Pen
      tonometry (P less than .05) or the mean increase of 16.5 mm Hg produced by
      Schiotz tonometry (P less than .01). There was no statistically significant
      difference between the intraocular pressure increase produced by Tono-Pen or
      Schiotz tonometry. Tonometry performed by inexperienced Tono-Pen users and
      experienced or inexperienced Schiotz users produced a significantly greater
      increase in intraocular pressure than that performed by experienced Tono-Pen
      users (P less than .05), and an extremely significant increase compared to
      tonometry performed by experienced or inexperienced Perkins users (P less than
      .01). The marked increase in intraocular pressure produced by Tono-Pen tonometry
      suggests that hand-held electronic applanation tonometers should be used with
      caution in eyes with a weakened cornea or sclera.

PMID- 1985493
TI  - A new method for documenting lens opacities.
AB  - We tested an anterior segment camera and digital analyzer on 32 eyes of 22
      patients to determine whether its measurement of lens opacities correlated with
      measurements obtained by a standardized clinical grading system. The lenses were
      graded clinically for nuclear opacity, nuclear color, cortical opacity, and
      posterior subcapsular opacity. The lenses were then photographed and analyzed
      with this new device, and the results were compared. The camera system showed
      good reproducibility. Its results correlated well with the clinical gradings for
      nuclear capacity (P = .001) and cortical opacity (P = .001) but less well with
      posterior subcapsular opacity (P = .3), although there were only seven eyes with
      posterior subcapsular opacities. This camera system could help document and
      follow up lens opacity with more accuracy and reproducibility than has been
      previously possible.

PMID- 1985494
TI  - Surgical management of oculomotor nerve palsy.
AB  - We treated seven patients with unilateral oculomotor nerve palsy by transposition
      of the insertion of the superior oblique tendon to a point anterior and medial to
      the insertion of the superior rectus muscle without trochleotomy (Scott
      procedure). Additionally, large recessions of the lateral rectus muscle of
      involved eyes and, occasionally, recess/resect procedures of horizontal recti
      muscles of non-involved eyes were performed. All patients were followed up
      between one and eight years. Orthophoria in the primary position was achieved and
      maintained with one operation in four patients. A fifth patient had only a small
      residual exotropia. In two patients who had aberrant regeneration of the
      oculomotor nerve, surgery on horizontal recti muscles of the noninvolved eye
      improved the eyelid position of the involved eye after three operations.

PMID- 1985495
TI  - Echographic diagnosis of dural carotid-cavernous sinus fistulas.
AB  - I used standardized ophthalmic echography to identify specific abnormalities in
      four patients with low-pressure, low-flow dural arteriovenous malformations. In
      all of the patients, B-scan ultrasonography showed engorgement of the ipsilateral
      vertical vein. A-scan ultrasonography dynamically imaged rapid blood flow through
      the superior ophthalmic vein and enlargement of the culpable ocular muscles in
      patients with restrictive ophthalmopathy. The 30-degree test distinguished
      between venous engorgement of the optic nerve sheath and apical compression of
      the optic nerve by enlarged ocular muscles.

PMID- 1985496
TI  - Causes of failure after initial vitreoretinal surgery for severe proliferative
      vitreoretinopathy.
AB  - We performed initial vitreoretinal surgery on 81 eyes with rhegmatogenous retinal
      detachments complicated by severe proliferative vitreoretinopathy. Of 81 eyes, 68
      (84%) had undergone previous scleral buckling. We performed vitreous base
      dissection on all 18 eyes (22%) that had anterior proliferative
      vitreoretinopathy. With one vitreoretinal operation, 66 of 81 eyes (81%) remained
      totally reattached. The main cause of initial anatomic failure and reoperation
      was either new or recurrent proliferation at the vitreous base. With additional
      vitreoretinal surgery and after a mean follow-up period of 19 months, 73 of 81
      retinas (90%) were totally reattached. The final causes of anatomic failure were
      anterior proliferative vitreoretinopathy and proliferation from relaxing
      retinotomies. Of the 73 successfully reattached eyes, 62 (85%) had postoperative
      visual acuity of 5/200 or better.

PMID- 1985497
TI  - Human and monkey corneal endothelium expression of low-density lipoprotein
      receptors.
AB  - Receptors for low-density lipoprotein are necessary for high-affinity uptake of
      lipid and protein essential to cell structure and function. Distinct receptors
      for acetoacetylated low-density lipoprotein internalize oxidized or enzymatically
      modified low-density lipoprotein and extracellular matrix components. We
      identified low-density lipoprotein receptors on cultured human and monkey corneal
      endothelial cells by the avid incorporation of fluorescently labeled low-density
      lipoprotein that was competitively inhibited by excess unlabeled low-density
      lipoprotein but not by unlabeled acetoacetylated low-density lipoprotein.
      Specific uptake of labeled low-density lipoprotein was greatest in nonconfluent,
      growing cells and increased after low-density lipoprotein deprivation. Intact
      endothelial monolayers of whole human cornea also incorporated low-density
      lipoprotein but not acetoacetylated low-density lipoprotein. After scratch injury
      of human corneas, spreading endothelium adjacent to areas of cell loss
      internalized more fluorescent low-density lipoprotein than cells distant from the
      injury. Blood-aqueous barrier breakdown occurring in ocular diseases and after
      surgical and nonsurgical trauma may allow leakage of circulating low-density
      lipoprotein, which provides a rich supply of lipid and protein for endothelial
      use. Efficient, receptor-mediated, low-density lipoprotein uptake may facilitate
      repair of damaged corneal endothelial membranes and regeneration of intact,
      functional cell monolayers.

PMID- 1985499
TI  - T-cell lymphoma involving subcutaneous tissue. A clinicopathologic entity
      commonly associated with hemophagocytic syndrome.
AB  - Eight cases of T-cell lymphoma localized primarily to the subcutaneous adipose
      tissue are described, five of which were referred in consultation with a benign
      diagnosis having been made or suggested. All patients presented with 1-12-cm
      diameter subcutaneous nodules, which preferentially involved the extremities in
      six individuals. Histologically, the lesions were reminiscent of panniculitis and
      were composed of a mixture of small and large atypical lymphoid cells (large
      cells predominated in four cases) infiltrating between adipocytes. Focally,
      sheets of tumor cells were found. Karyorrhexis, fat necrosis, and benign
      histiocytes were present in all cases. Involvement of small blood vessels was
      found in seven cases, but the infiltrates were not primarily angiocentric, and
      angiodestruction was minimal or absent. Immunophenotypic analysis (paraffin or
      frozen sections) in all cases showed that the atypical cells were of T-cell
      phenotype. Frozen-section studies demonstrated a mature T-cell phenotype with
      evidence of pan-T-cell antigen loss in two of five lesions. Genotypic analysis
      demonstrated a rearrangement of the T-cell receptor beta-chain gene in one
      (possibly two) biopsies of three cases studied. All patients had some evidence of
      hemophagocytosis during their clinical course. Six patients developed a florid
      hemophagocytic syndrome, fatal in five patients. Autopsies were done in all of
      the expired patients, and all had residual subcutaneous lymphoma and a
      hemophagocytic syndrome. Dissemination to nonsubcutaneous sites did not occur.
      Three patients are currently alive without evidence of lymphoma after aggressive
      chemotherapy (mean follow-up, 12 months). These results suggest that T-cell
      lymphomas that are primarily localized to the subcutaneous tissue may represent a
      distinct clinicopathologic entity. Initial biopsy findings may be misinterpreted
      as benign. A hemophagocytic syndrome commonly supervenes that may be secondary to
      lymphokine production by the malignant cells or related to the destruction of
      normal cells at subcutaneous sites.

PMID- 1985498
TI  - Epidemiologic characteristics, predisposing factors, and etiologic diagnosis of
      corneal ulceration in Nepal.
AB  - Corneal ulceration is one of the most frequent causes of blindness in developing
      countries. Between September 1985 and August 1987, 405 patients with corneal
      ulceration were examined at Tribhuvan University Teaching Hospital in Kathmandu,
      Nepal. Males and females were equally affected. The most common predisposing
      cause of ulceration was corneal trauma, usually with organic agricultural
      materials. Microorganisms were grown from 324 (80%) of the ulcers. Pure bacterial
      cultures were obtained from 256 (63.2%) of the patients, whereas pure fungal
      cultures were obtained from 27 (6.7%) of the patients. In 41 patients (10.1%),
      corneal cultures yielded a mixed growth of bacteria and fungi. Of a total of 398
      bacterial isolates, 124 (31.1%) were positive for Streptococcus pneumoniae, the
      most commonly isolated organism in the series. Other frequently isolated bacteria
      included Staphylococcus epidermidis, S. aureus, and Pseudomonas species. Of 68
      positive fungal isolates obtained, 32 (47.0%) were identified as Aspergillus
      species. Candida species and Fusarium species were less commonly seen.

PMID- 1985500
TI  - Diffuse panbronchiolitis in North America. Report of three cases and review of
      the literature.
AB  - Diffuse panbronchiolitis is a disease largely restricted geographically to Japan.
      It is manifested clinically by an insidious onset of dyspnea, cough, and
      production of mucopurulent sputum. Histologically it is characterized by a
      suppurative bronchiolitis involving primarily the respiratory and terminal
      bronchioles with subsequent progression to bronchiolectasis. Pulmonary function
      tests show a mixed obstructive-restrictive pattern. This report presents two
      cases occurring in white patients and one in an Oriental immigrant to Canada.

PMID- 1985501
TI  - Primitive polypoid granular-cell tumor and other cutaneous granular-cell
      neoplasms of apparent nonneural origin.
AB  - Most cutaneous and noncutaneous granular-cell tumors are currently thought to be
      of Schwann-cell derivation. We present seven unusual cutaneous granular-cell
      lesions in which Schwann-cell origin can be excluded or is inapparent. Four of
      these lesions are of a previously undescribed type, and, unlike conventional
      granular-cell tumors of the skin, show a polypoid configuration, numerous
      mitoses, cytologic atypia, and a primitive immunophenotype. We propose the term
      "primitive polypoid granular-cell tumor" for these lesions. One occurred in a
      child, and three in adults. There have been no metastases to date, with follow-up
      periods of 2, 4, 4, and 16 years, respectively, although one tumor recurred
      locally. Additional cases and longer follow-up may be required to rule out the
      possibility that primitive polypoid granular-cell tumor is a low-grade
      malignancy. Two other granular-cell lesions represent variants of leiomyosarcoma,
      one of which widely metastasized. The last case is a granular-cell form of
      nodular basal-cell carcinoma. Cutaneous granular-cell neoplasms can show varying
      differentiation and behavior. Pathologists should not equate the occurrence of
      cytoplasmic granularity in a cutaneous neoplasm with the diagnosis of granular
      cell schwannoma.

PMID- 1985502
TI  - Saline-filled cuffs help prevent laser-induced polyvinylchloride endotracheal
      tube fires.
AB  - To determine whether the filling of tracheal tube cuffs with saline would
      decrease their combustibility during laser surgery, 20 polyvinylchloride tracheal
      tubes were studied. The cuffed end of each tracheal tube was inserted into the
      neck of an empty flask, and the tube and flask were flushed with oxygen for 5 min
      before cuff inflation. Ten tracheal tubes had their cuffs inflated with air, and
      10 were inflated with saline. A Lasersonics LS880 CO2 laser, set to 5 W for five
      of each of the two types of filled cuffs and to 40 W for the other pair of five
      tubes, was fired continuously at the cuffs for up to 1 min. No combustion
      occurred at the 5-W setting. The times to cuff perforation when the laser was set
      at 5 W were (mean +/- SD) 1.00 +/- 0.83 and 4.21 +/- 3.91 s for the air- and
      saline-filled cuffs, respectively, a difference that was not statistically
      significant. The time to deflation of the saline-filled cuff (104.6 +/- 67.5 s)
      was, however, significantly longer than that of the air-filled cuff (2.59 +/-
      1.97 s). When the tracheal tube cuffs were exposed to 40-W laser radiation, the
      cuff and adjacent tube shaft ignited in all cases when the cuffs were inflated
      with air, but only in one of five cases when the cuffs were filled with saline (P
      less than 0.05). The filling of tracheal tube cuffs with saline provides simple,
      moderately effective partial protection of the cuff of endotracheal tubes during
      CO2 laser airway surgery.

PMID- 1985503
TI  - Effect of intraoperative analgesic therapy on end-expired concentrations of
      halothane associated with spontaneous eye opening in children.
AB  - We studied 94 healthy ASA physical status I or II children to determine the end
      expired concentration of halothane associated with eye opening on emergence from
      anesthesia, and to determine if parenteral opioid therapy or regional analgesia
      significantly altered this concentration. In our study, anesthesia was maintained
      with halothane in an air-oxygen mixture. After the surgical procedure was
      completed, the inspired concentration of halothane was adjusted to zero and the
      end-expired concentrations were permitted to decrease spontaneously. The end
      expired concentration at which the child spontaneously opened his or her eyes was
      recorded. There were no statistically significant differences in the values of
      the end-expired halothane concentration at eye opening between patients in the
      control group, who did not receive any supplementation of halothane anesthesia,
      and patients in the groups that received either morphine supplementation or
      regional analgesia. These data suggest that analgesia and hypnosis (or loss of
      consciousness) occur by different mechanisms during halothane anesthesia in
      children.

PMID- 1985504
TI  - Clinical responses to ORG 9426 during isoflurane anesthesia.
AB  - To determine average dose requirements and pharmacodynamic characteristics before
      general clinical use, the dose-response curve, onset time, and recovery time for
      the neuromuscular relaxant ORG 9426 were determined in 72 adult patients given
      doses of 120, 160, 200, or 240 micrograms/kg after establishment of a steady
      state expired isoflurane concentration of approximately 1%. Neuromuscular
      blockade was continuously recorded using the ulnar evoked electromyogram. Using
      the log probit method, ED95 was 268 micrograms/kg, ED90 was 251 micrograms/kg,
      and ED50 was 144 micrograms/kg. The time until 80% blockade was 1.9 min at 240
      micrograms/kg, and the average time to peak effect was 4.6 min, which did not
      vary with dose. The clinical duration (injection until T1 returned to 25%) was
      20.5 min, and the recovery index (T1 increased from 25% to 75% of control) was
      15.4 min, after a total dose of 300 micrograms/kg. The duration of 75
      micrograms/kg and 100-micrograms/kg repeat (maintenance) dose was 14.6 and 17.8
      min, respectively, and no cumulative effect was apparent after as many as five
      maintenance doses. No cardiovascular side effects were seen at doses used in the
      study. We conclude that ORG 9426 is a nondepolarizing muscle relaxant with a
      rapid onset and short duration of action that deserves further clinical
      evaluation.

PMID- 1985505
TI  - Cardiorespiratory effects of antagonism of diazepam sedation with flumazenil in
      patients with cardiac disease.
AB  - The specific benzodiazepine antagonist flumazenil is currently under intense
      study. Despite much clinical experience, no detailed invasive hemodynamic studies
      of its use in cardiac patients have been published. In the present study,
      hemodynamic and respiratory variables were measured in 10 cardiac patients
      undergoing catheterization of the right and left sides of the heart, before and
      after sedation with intravenous diazepam, and after reversal of sedation with
      flumazenil. A sleep dose of diazepam (12.2 +/- 5.1 mg, mean +/- SD) caused only
      slight decreases in mean arterial pressure (103 +/- 12 to 98 +/- 14 mm Hg; P less
      than 0.05), pulmonary capillary wedge pressure (13.2 +/- 6.3 to 11.7 +/- 6.6 mm
      Hg; P less than 0.05), and left ventricular end-diastolic pressure (20.8 +/- 7.5
      to 17.3 +/- 10.0 mm Hg; P less than 0.05), with no significant changes in
      respiratory gas homeostasis. Intravenous flumazenil (0.22 +/- 0.07 mg) resulted
      in spontaneous awakening and return to full orientation, yet caused no
      significant alteration in either hemodynamic or respiratory variables measured.
      Reversal of diazepam-induced sedation by flumazenil in cardiac patients appears
      safe and effective.

PMID- 1985507
TI  - Is hypoxic pulmonary vasoconstriction exaggerated during one-lung ventilation in
      patients with patent ductus arteriosus?

PMID- 1985506
TI  - Comparison of percutaneous losses of sevoflurane and isoflurane in humans.
AB  - We studied the percutaneous losses of sevoflurane and isoflurane during
      administration and elimination in seven healthy male volunteers. Anesthesia was
      induced and maintained with fentanyl, midazolam, and/or thiopental, and nitrous
      oxide for 30 min, after which 1% sevoflurane and 0.4% isoflurane in 65% nitrous
      oxide were administered for 30 min. Inspired, end-tidal, and mixed-expired gas
      samples were collected during administration and for 5-7 days of elimination. To
      measure percutaneous loss, each subject's arm was enclosed in a glass cylinder
      sealed at both ends and with two ports, one for flushing with nitrogen and one
      for obtaining gas samples during the 30 min of administration and the first 150
      min of elimination. Anesthetic concentrations in all samples were determined
      using gas chromatography. The surface area of the arm was measured and the total
      surface area was calculated. During administration and elimination, percutaneous
      loss of isoflurane was significantly greater than that of sevoflurane (P less
      than 0.05). For both volatile agents, losses during elimination were greater than
      during administration (P less than 0.05), but even when combined, these losses
      were too small to affect kinetic or metabolic studies based on mass balance.

PMID- 1985508
TI  - Nearly fatal cardiovascular collapse during total hip replacement: probable
      coronary arterial embolism.

PMID- 1985509
TI  - Brainstem toxicity with reversible locked-in syndrome after intrascalene brachial
      plexus block.

PMID- 1985510
TI  - Spinal anesthesia in a patient with Friedreich's ataxia.

PMID- 1985511
TI  - Myocardial infarction accompanying acute clonidine withdrawal in a patient
      without a history of ischemic coronary artery disease.

PMID- 1985512
TI  - Prevention of nitrous oxide-induced increases in endotracheal tube cuff pressure.

PMID- 1985513
TI  - Everything old is new again.

PMID- 1985514
TI  - Neurally evoked compound electromyogram in the clinical setting.

PMID- 1985515
TI  - Modification to an anesthesia breathing circuit to prolong monitoring of gases
      during the use of humidifiers.

PMID- 1985516
TI  - Endobronchial cuff pressures of double-lumen tubes.

PMID- 1985517
TI  - Reuse of a disposable stylet with life-threatening complications.

PMID- 1985518
TI  - The burden of progress: a fable.

PMID- 1985519
TI  - Anesthesia mortality in perspective.

PMID- 1985520
TI  - Endotracheal tube cuff failure due to valve damage.

PMID- 1985521
TI  - Arytenoid subluxation: diagnosis and treatment.
AB  - Both arytenoid subluxation and recurrent laryngeal nerve paralysis (RLNP) may
      result from injury to the larynx, and they may be difficult to distinguish
      clinically. A patient with arytenoid subluxation who was initially believed to
      have RLNP was treated with medialization laryngoplasty 1 year after the injury.
      Preoperative magnetic resonance imaging and computed tomography effectively
      demonstrated the cricoarytenoid subluxation, which was confirmed by
      intraoperative electromyography (EMG) showing normal electrical activity in the
      thyroarytenoid muscle. Photographs from preoperative fiberoptic laryngoscopy are
      presented to identify the appearance of arytenoid subluxation. Computed
      tomographic findings and photographs from laryngoscopy of two patients with RLNP
      documented by intraoperative EMG evaluation are presented to help distinguish the
      clinical appearance of this disorder from arytenoid subluxation. An integrated
      approach to the diagnosis and treatment of arytenoid subluxation is presented.

PMID- 1985522
TI  - Recurrent laryngeal nerve avulsion for treatment of spastic dysphonia.
AB  - Treatment of spastic dysphonia by recurrent laryngeal nerve section has resulted
      in reproducibly good results in the early postoperative period in most patients.
      However, critical long-term follow-up has shown a high recurrence rate of
      adductor spasms by the third year after initial nerve section. A patient who
      developed recurring adductor spasms 1 year after nerve section was reexplored,
      with identification of neural regrowth into the distal segment of the recurrent
      laryngeal nerve. The technique of neural avulsion removing the distal nerve up to
      its insertion into the laryngeal muscles is described. Neural regrowth, which is
      just one of the possible mechanisms for recurrence of spastic dysphonia, should
      be prevented by this surgical modification. Twelve patients who have undergone
      neural avulsion primarily for spastic dysphonia are being followed up without
      recurrence of symptoms thus far. Although these results appear promising, this
      short follow-up that averages 1.5 years must be extended to firmly support these
      concepts.

PMID- 1985523
TI  - Electrical pacing for dynamic treatment of unilateral vocal cord paralysis.
      Experiment in long-denervated muscle.
AB  - In order to explore the possibility of clinical application of laryngeal pacing
      as a treatment for unilateral vocal cord paralysis, we examined the reactivity of
      atrophic muscle to electrical stimulation in dogs whose recurrent laryngeal
      nerves were damaged by crushing, dissection followed by resuturing, or a 3-cm
      neurectomy. The threshold level to induce enough vocal cord adduction reached the
      maximum at 2 weeks after nerve injury, decreased with time, and never surpassed 7
      V in each case. On the basis of results of these preliminary probings, laryngeal
      pacing was conducted on a dog 15 months after resection of the laryngeal nerve.
      Adduction of the paralyzed vocal cord for synchrony with the intact cord was
      achieved by 7 V of electrical stimulation of the thyroarytenoid muscle that was
      triggered by signals from the cricothyroid muscle.

PMID- 1985524
TI  - Supraglottic contributions to pitch raising. Videoendoscopic study with
      spectroanalysis.
AB  - Several questions pertaining to pitch raising recur frequently. Does the larynx
      rise with the production of higher frequencies? What happens to the pharyngeal
      walls between the soft palate and the larynx when the fundamental frequency is
      raised? How does the soft palate participate in pitch raising? To answer these
      questions, the present study was undertaken with the recently described
      simultaneous velolaryngeal endoscopy technique. Nine professional singers were
      asked to find the limits of their vocal range in any of six voice qualities:
      speech, falsetto, cry/sob, twang, belting, and opera. Simultaneous activities of
      the larynx, the pharyngeal walls, and the soft palate were submitted to
      videoendoscopy with synchronous voice recording and studied with spectroanalysis
      of discrete segments of the total phonation range. Our dual endoscopic study
      showed that 1) the larynx rose in all subjects with the production of higher
      frequencies, 2) with the highest fundamental frequency, the lateral pharyngeal
      walls significantly contracted toward the midline in an "upside-down V shape,"
      creating a very narrow pharyngeal tube, and 3) the soft palate lifted and the
      velopharyngeal port narrowed considerably with higher frequencies.

PMID- 1985525
TI  - Electrosurgery-induced endotracheal tube ignition during tracheotomy.
AB  - Electrosurgery was the most common source of ignition for operating room fires
      prior to the advent of lasers. When combined with volatile anesthetic mixtures,
      electrosurgery has caused ignition of plastic, rubber, paper, enteric gases, and
      combustible preparation solutions. We report on an intubated patient whose
      polyvinyl chloride endotracheal tube ignited during a tracheotomy performed with
      an electrosurgical unit. The oxygen-rich environment, the polyvinyl chloride
      tube, and the heat generated by the electrosurgical unit combined to produce a
      fire. Since otolaryngologists are called upon often to perform tracheotomies on
      intubated patients, it is imperative that they understand the factors involved in
      the development of such a fire. This case is presented with an explanation of why
      this type of fire occurs. A brief review of the literature is included. Different
      kinds of electrosurgical units, precautions as to their use, and the management
      of electrosurgery-induced endotracheal tube fires are also discussed.

PMID- 1985526
TI  - Laryngeal changes during exercise and exercise-induced asthma.
AB  - Exercise-induced asthma is defined as bronchospasm within the distal airways
      initiated by exercise. Whether the larynx responds to produce an exacerbation or
      alleviation of symptoms during an attack has never been evaluated. Thirty
      subjects were tested, including 15 normals and 15 with exercise-induced asthma.
      Laryngeal response to exercise was determined by measuring the area of the
      glottic aperture before, during, and after exercise. The glottis was visualized
      with a flexible laryngoscope and video images were recorded during monitoring of
      respirations. Asthma was induced in subjects by having them exercise on an
      ergometer for 10 minutes while breathing dry air at 10 degrees C. Measurements
      were subsequently made from recorded images and relative glottic areas were
      compared between groups. Our data quantify the normal physiologic response of the
      larynx to exercise and demonstrate a substantial laryngeal contribution to asthma
      induced by exercise.

PMID- 1985527
TI  - Magnetic resonance imaging and computed tomography in pediatric head and neck
      masses.
AB  - Fifty-three magnetic resonance imaging (MRI) and 25 computed tomography (CT)
      studies of 53 head and neck masses in pediatric patients were reviewed
      retrospectively. All lesions had pathologic proof except for 2 metastatic and 2
      recurrent lesions, which only had prior pathologic confirmation at their primary
      sites. These included 12 malignant tumors, 23 benign tumors, 6 inflammatory
      masses, and 12 congenital lesions. The MRI performance ranged predominantly from
      good to excellent in detection of the lesion and the extent of involvement and in
      contrast to the surrounding tissue; when CT comparison was available, MRI proved
      to be equal to or better than it in detection of these factors and in
      preoperative diagnosis. Our results suggest that MRI should be the method of
      choice for the initial evaluation of the pediatric head and neck region,
      especially in those patients requiring multiple examinations. However, CT and MRI
      should be used conjunctively in complicated cases, especially those possibly
      involving lesions with calcifications or bony involvement.

PMID- 1985528
TI  - Effect of head extension on equilibrium in normal subjects.
AB  - A dynamic posturography system was used to test the effect of 55 degrees head
      extension on postural sway in 20 normal subjects. There was a highly significant
      increase in sway with head extension under two conditions; in both, the support
      surface moves proportionally to body sway angle (sway-referenced feedback). The
      largest increase in sway occurred when the eyes were closed and the support
      surface was sway-referenced. This latter condition removes vision, reduces the
      effectiveness of ankle proprioception, and forces the subject to depend mostly on
      vestibular information for equilibrium. We suggest that head extension increases
      sway because the utricular otoliths are put into a disadvantageous position. This
      may be another example of the role of utricular input in the control of balance.

PMID- 1985529
TI  - Vertical partial laryngectomy: a critical analysis of local recurrence.
AB  - The purpose of this study was to evaluate local recurrence following vertical
      partial laryngectomies in 416 patients with either T1N0M0 or T2N0M0 glottic
      carcinoma. Local failure was reported according to the T stage, the precise tumor
      location within each stage, the true vocal cord mobility, and the surgical
      procedure performed. No local recurrences were observed among 42 patients who
      underwent thyrotomy and cordectomy when the tumor was confined to the middle
      third of the mobile true vocal cord. Local failure occurred in 8 of 111 (7.2%)
      patients in whom hemilaryngectomy was performed for tumors confined to one mobile
      true vocal cord. There was a diverse group of lesions within each T stage that
      responded differently to the surgical approaches. The differences in the initial
      recurrence rates are discussed in terms of careful preoperative assessment and
      choice of surgical technique for early glottic carcinoma.

PMID- 1985530
TI  - Effect of aldosterone antagonist on the DC potential in the endolymphatic sac.
AB  - The effect of aldosterone and canrenoate, known as an aldosterone antagonist, on
      the DC potential in the endolymphatic sac (ESP) was examined in the guinea pig.
      Intravenous administration of aldosterone (1 mg/kg) induced no change in the ESP
      for 60 minutes after the injection. However, canrenoate, an aldosterone
      antagonist, produced a dose-dependent decrease in the ESP. Pretreatment with
      aldosterone attenuated the decrease in the ESP by canrenoate. The results suggest
      the possibility that aldosterone may play a role in the endolymph absorption of
      the endolymphatic sac.

PMID- 1985531
TI  - Hemangioma of the temporalis muscle.
AB  - A rare case of an intramuscular hemangioma of the temporalis muscle is reported.
      The clinical examination, carotid arteriogram, computed tomographic scan, and
      aspiration cytology suggested the vascular nature of the tumor, but an exact
      diagnosis could only be made after histopathologic examination. Temporary
      occlusion of the ipsilateral external carotid artery and subperiosteal dissection
      permitted complete, wide excision without much bleeding.

PMID- 1985532
TI  - Computed tomographic diagnosis of septic lateral sinus thrombosis.

PMID- 1985533
TI  - Undifferentiated carcinomas of salivary glands.
AB  - Undifferentiated carcinomas of salivary glands are those epithelial malignancies
      whose light-optic histopathologic features are not sufficient to place them in
      other defined classes of carcinoma. They are ultrastructurally heterogeneous and
      can manifest neuroendocrine differentiation. With or without the latter, the
      carcinomas are biologically high-grade and rank with salivary duct and high-grade
      mucoepidermoid carcinomas in terms of morbidity and mortality.

PMID- 1985534
TI  - Computerized identification of pathologic duodenogastric reflux using 24-hour
      gastric pH monitoring.
AB  - Duodenogastric reflux is a naturally occurring sporadic event, the incidence,
      occurrence, and detrimental effects of which have been difficult to assess. The
      reliability of 24-hour gastric pH monitoring to detect duodenogastric reflux was
      studied. Central to the use of pH monitoring for this purpose is confidence in
      its ability to measure and display pH data in a way that reflects changes in the
      gastric pH environment with sufficient sensitivity. To test this the gastric pH
      of 10 dogs was measured in the fasting state, after feeding, and after
      pentagastrin stimulation. The antrum was more alkaline in the fasting state (p
      less than 0.01) and the display of data by frequency distribution graph was
      sensitive enough to reflect induced pH changes. To test the consistency of
      gastric pH at a given position, simultaneous 24-hour gastric monitoring was
      performed in 12 normal subjects with two probes placed at either 5 or 10 cm below
      the lower esophageal sphincter. Only at the 5-cm position did the two probes read
      within 1 pH unit of each other more than 90% of the time. Based on these
      principles, gastric pH monitoring was performed 5 cm below the lower esophageal
      sphincter in 30 normal subjects and 11 patients, fulfilling Ritchie's clinical
      criteria for pathologic duodenogastric reflux. The data obtained was arranged
      into 71 variables and subjected to discriminant analysis. Sixteen variables were
      identified, each with a corresponding coefficient to be used as a multiplier to
      derive a score. A score of more than +2.2 indicated a high probability of
      pathologic duodenogastric reflux. The test was applied to a validation population
      consisting of 10 additional normal subjects and 10 patients meeting Ritchie's
      criteria. All normal subjects had a normal score and all but one (90%) of the
      patients had an abnormal score. When compared to O-diisopropyl iminodiacetic acid
      (DISIDA) scintigraphy in another group of 22 normal subjects and 60 patients, 24
      hour gastric pH monitoring was superior in the detection of pathologic
      duodenogastric reflux. The study shows how the application of computer technology
      can be used to diagnose pathologic duodenogastric reflux in patients with complex
      foregut complaints.

PMID- 1985535
TI  - Intra-abdominal abscess in regional enteritis.
AB  - Intra-abdominal abscess (IAA) developed in 129 of 610 patients (21.2%) with
      Crohn's disease confined to the small bowel. The location of the abscess was
      intraperitoneal (IPA) in 109 (17.9%) and retroperitoneal (RPA) in 20 (3.3%).
      There was a marked preponderance of male patients in the retroperitoneal group
      (ratio, 18:2) (p less than 0.0001). All 129 patients were operated on. Thirteen
      of one hundred nine patients (12%) with IPA were reoperated on for recurrent
      abscess, and nine (8.2%) for other reasons. External fistula developed in 24
      patients (22%) after simple incision and drainage. Four (3.7%) died; one from
      hepatitis, and three from sepsis 5, 14, and 90 days after surgery. Of the 20
      patients with RPA, two (10%) were reoperated on for recurrent abscess and four
      (20%) for other reasons. External fistula developed in two patients (10%). There
      were no deaths in this group. A small number of patients with IAA complicating
      regional enteritis had persistent sepsis causing postoperative death, which is,
      however, six times lower than in our comparable series of Crohn's (ileo)colitis.

PMID- 1985536
TI  - Risks of intestinal anastomoses in Crohn's disease.
AB  - Six hundred fifty-eight intestinal anastomoses in 429 operations for Crohn's
      disease were studied prospectively during an 8-year period to detect variables
      connected with perioperative morbidity. Postoperative complications occurred in
      9.7% of the patients, 4% had to be reoperated on, and the overall mortality rate
      was 0.5%. In multivariate analysis by stepwise logistic regression, the only
      variable significantly (p = 0.03) associated with overall rate of complications
      was long-term corticosteroid therapy. Serious complications were more common in
      cases of intra-abdominal abscesses (p = 0.01) and preoperative steroid medication
      (p = 0.03). The combination of both of these risk factors increased the rate of
      reoperations from 0.6% (no steroids, no abscess) to 16% (steroids and abscess).
      No significant association with postoperative complications could be found for
      age, sex, duration of disease, previous operations, nutritional status, emergency
      surgery, extent of disease, type, number, and localization of anastomoses,
      presence of proximal ileo-/colostomy, or histologically inflamed margins of
      resection.

PMID- 1985537
TI  - A clinical pilot study combining surgery with intraoperative pelvic
      hyperthermochemotherapy to prevent the local recurrence of rectal cancer.
AB  - Intraoperative pelvic hyperthermochemotherapy (IOPHC) with mitomycin C (MMC) was
      prescribed for 14 patients with resectable advanced rectal cancer in an attempt
      to prevent a postoperative local recurrence. Immediately after rectal amputation
      and extended lymphadenectomy, IOPHC was performed using physiologic saline
      containing 40 micrograms/mL of MMC at 45.5 +/- 0.6 C for 90 minutes, with an
      apparatus devised for IOPHC. At the end of IOPHC, the esophageal temperature was
      37.2 +/- 0.8 C and cooling was not required. Antitumor efficacy and complications
      in the IOPHC group were compared with findings in 12 rectal cancer patients who
      underwent surgery only within the same period of time. Operation time was not
      prolonged with IOPHC treatment. In cytologic examinations of the pelvic lavage
      just before IOPHC treatment, viable cancer cells were detected in 6 of the 14
      patients but were never detected in the postoperative exudate drained from the
      pelvic cavity. Of the 12 patients in the control group, 2 had a local recurrence,
      while in the IOPHC group there was no local recurrence for 16.9 +/- 9.7 months at
      this writing. Postoperative complications did not differ between the groups. This
      IOPHC treatment is a favorable method in eradicating cancer cells for
      postoperative local recurrence of rectal cancer.

PMID- 1985538
TI  - Liver transplantation in children.
AB  - Although liver transplantation is now accepted as the ideal therapy for end-stage
      liver disease, relatively few centers have gained a large experience in children,
      and good results have been elusive. Technical difficulty and a high incidence of
      graft failure are among the obstacles to success. At the University of California
      at Los Angeles, 39% of our liver transplants are in the patients who are younger
      than 18 years. We have analyzed our experience with 103 patients to emphasize
      factors important to a favorable outcome with the procedure. One hundred twenty
      three transplants were performed in 103 children (mean age, 5.2 years; 48%
      younger than 3 years). No reduced-size grafts were used. Scrupulous attention to
      technical details of the vascular reconstruction, including frequent use of the
      supraceliac aorta of the recipient and interrupted suture techniques, ensured
      construction of sound hepatic artery and portal vein anastomoses at the first
      operation. Preoperative exchange transfusions were used if the prothrombin time
      was prolonged beyond 7 seconds, resulting in an average blood loss of only 3.3
      volumes. Cyclosporine dosage was maintained in the high therapeutic range for the
      first 4 weeks, and anti-T-cell antibody (OKT3) was used for rejection (38%).
      Amphotericin prophylaxis was used for biliary atresia patients with multiple
      previous operations. Eighty-two of one hundred three patients (80%) are alive.
      There were no intraoperative deaths. Actuarial survival rates at 6 months, 1
      year, and 5 years are 80%, 79%, and 77%, respectively. Survival of patients who
      underwent transplantation at age less than 1 year is 65% versus 85% at age more
      than 1 year (p = 0.08). Retransplantation was performed in 19 patients (18%),
      with a survival rate of 58%. Hepatic artery thrombosis, the most frequent
      technical complication, occurred in only 16 patients (13%). Survival rates of ABO
      identical-match versus nonidentical-match grafts were 96% and 60%, respectively
      (p = 0.02). Graft survival was only 47% if more than one steroid cycle was
      needed, compared to 75% survival with OKT3 treatment. Despite impairment of renal
      function (glomerular filtration rate [GFR] less than 80 cc/kg/min) in 54% of
      patients and hypertension requiring therapy in 27%, 90% of the children
      demonstrated enhancement of growth, development, and functional status. The
      following conclusions were made. (1) Pediatric liver transplantation is the
      treatment of choice for all types of end-stage liver disease and should be
      considered early. (2) Factors that enhance survival include technical precision,
      aggressive retransplantation, antifungal chemoprophylaxis and therapy, and
      judicious immunosuppression with use of OKT3 for rejection.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 1985539
TI  - Locally recurrent parathyroid neoplasms as a cause for recurrent and persistent
      primary hyperparathyroidism.
AB  - Between 1982 and 1989, 145 patients underwent operations for persistent or
      recurrent primary hyperparathyroidism (HPT). At re-exploration, 15 patients
      (10.3%) were found to have locally recurrent parathyroid tumors (11 patients with
      adenoma and 4 with carcinoma). These 15 patients had 28 previous operations at
      outside institutions for HPT. Patients with locally recurrent HPT secondary to
      adenoma had a longer disease-free interval than patients with locally recurrent
      carcinoma. At the time of evaluation at the National Institutes of Health (NIH)
      for recurrent or persistent HPT, each patient was symptomatic and patients with
      carcinoma had significantly more symptoms and higher serum levels of calcium and
      parathyroid hormone than patients with adenoma. Locally recurrent parathyroid
      neoplasm was correctly localized by preoperative testing in 14 of 15 patients.
      These 15 patients underwent 18 reoperations at NIH for excision of locally
      recurrent parathyroid tumors. Following the final reoperation (two patients had
      more than one procedure), each patient had normal serum levels of calcium. In
      addition each patient remains biochemically cured (based on normal serum calcium
      level), with a median follow-up interval of 21 months. Local recurrence of
      parathyroid adenoma comprises a small but significant proportion of cases of
      recurrent or persistent HPT and can be indistinguishable from parathyroid
      carcinoma. Findings suggestive of carcinoma include shorter disease-free
      interval, higher serum levels of calcium and parathyroid hormone, and histologic
      appearance. Whether the locally recurrent parathyroid neoplasm is benign or
      malignant, aggressive surgery can control serum levels of calcium in these
      patients with acceptable rates of morbidity.

PMID- 1985540
TI  - Metabolic changes in patients severely affected by tetanus.
AB  - Metabolic changes in six severely affected tetanus patients suffering from
      characteristic labile hypertension (maximum systolic blood pressure greater than
      200 mmHG, maximum diurnal change in systolic pressure greater than 100 mmHg) were
      investigated. Daily urinary excretion of urea nitrogen increased gradually from
      the onset of opisthotonus, reached a peak value (10.4 to 15.4 g/m2) in 8 to 20
      days, and decreased subsequently. Average cumulative excretion in 30 days reached
      239.6 +/- 32.7 g/m2. Urine catecholamine excretion was elevated in each patient
      and remained elevated during this period. Plasma cortisol and glucagon
      concentrations were not increased markedly except in a case complicated other
      systemic bacterial infection. Increased protein catabolism in these patients
      could not be explained by the metabolic effects of 'stressed hormones' alone, and
      neurologic factors must be considered.

PMID- 1985541
TI  - Congenital tracheal stenosis with unilateral pulmonary agenesis.
AB  - Cogenital tracheal stenosis with unilateral pulmonary agenesis is a rate and
      frequent fetal combination. In an 8-year period, 5 infants (ages 2 to 6 months)
      with these anomalies were treated. The presenting signs and symptoms consisted of
      wheezing, stridor, and tachypnea and included frank respiratory failure requiring
      emergency therapy in several patients. The operative repair consisted of
      segmental resection and anastomosis in one patient, and rib-cartilage
      tracheoplasty in the other four. Two infants died, one of cerebral hypoxia, and
      the other of aortotracheal fistula. Long-term follow-up in the three survivors is
      satisfactory.

PMID- 1985542
TI  - Synthesis of type I collagen in healing wounds in humans.
AB  - To quantify wound healing in surgical patients, samples of wound fluid were
      collected through a silicone rubber tube for 7 postoperative days and their
      concentrations of the carboxyterminal propeptide of type I procollagen (PICP) and
      the aminoterminal propeptide of type III procollagen (PIIINP) were measured with
      specific radioimmunoassays. The mean concentration of PICP in would fluid on day
      1 was 207 +/- 92 (SD) micrograms/L, and on day 2 908 +/- 469 micrograms/L (p less
      than 0.001, signed rank test). On day 7, the mean concentration reached was 380
      times higher than that of day 1 (79,330 +/- 54,151 micrograms/L). Only one peak
      of PICP antigenicity, corresponding to the intact propeptide as set free during
      synthesis of type I procollagen, was detected on Sephacryl S-300 gel filtration
      analysis of wound fluid samples. The mean concentration of PIIINP was 70 +/- 61
      micrograms/L on day 1, 86 +/- 88 micrograms/L on day 2, and 180 +/- 129
      micrograms/L on day 3 (p less than 0.001 when compared with day 1). Finally on
      day 7, a 250-fold concentration (17,812 +/- 9839 micrograms/L), compared with day
      1, was reached. Methods described in the present paper allow separate and
      repetitive quantification of the synthesis of both type I and type III
      procollagen during human wound healing.

PMID- 1985543
TI  - Role of granulocyte elastase in tissue injury in patients with septic shock
      complicated by multiple-organ failure.
AB  - To better understand the role of granulocyte elastase (GE) in mediating tissue
      injury during sepsis, GE levels were measured in plasma and bronchoalveolar
      lavage fluid (BALF) in patients with septic shock (n = 16) and hemorrhagic shock
      (n = 30). Granulocyte elastase levels were compared to levels of alpha 1-protease
      inhibitor (alpha 1-PI). Results show that although plasma GE-alpha 1-PI complex
      was initially elevated in patients with hemorrhagic and septic shock, elevations
      in plasma GE-alpha 1-PI complex (831 +/- 241 micrograms/L) persisted in septic
      shock patients. alpha 1-Protease inhibitor levels in serum were increased,
      resulting in an inhibition of serum GE activity. Granulocyte elastase activity in
      BALF, however, was significantly higher in those patients with septic, as
      compared to hemorrhagic shock (31.4 +/- 25.8 versus 3.7 +/- 4.0 U/L,
      respectively). In addition GE levels were compared to other parameters, including
      respiratory index, blood neutrophil count, and plasma levels of endotoxin,
      fibronectin, and coagulation factor XIII. Significant correlations were observed
      between GE-alpha 1-PI and increased endotoxin concentration and decreased
      fibronectin and coagulation factor XIII levels. Significant correlation was found
      also between GE activity in BALF and respiratory index. These findings suggest
      that severe tissue damage occurred in patients with septic shock complicated by
      multiple-organ failure. Although GE activity appeared to be adequately inhibited
      by alpha 1-PI in blood, increased GE activity in local tissues, such as lung
      alveoli, may be responsible for significant local tissue injury during septic
      shock.

PMID- 1985544
TI  - Triiodothyronine in the recovery of stunned myocardium in dogs.
AB  - Two groups of dogs were subjected to a 15-minute period of regional myocardial
      ischemia by snaring the left anterior descending coronary artery proximal to its
      first diagonal branch. After release of the snare, the dogs were given either
      placebo (group 1: n = 7) or triiodothyronine (T3) therapy (group 2: n = 6). The
      dose of T3 given was 0.2 microgram/kg at 30-minute intervals to a total of six
      doses. Plasma free T3 level fell significantly during the ischemic period in both
      groups and continued to fall after reperfusion in group 1. In both groups,
      cardiac function deteriorated significantly during the period of ischemia and
      rapidly returned to control level after reperfusion. After 90 minutes of
      reperfusion, however, deterioration of left ventricular function was observed in
      group 1 and was significantly worse than in group 2, in which hemodynamic
      function was maintained and, in fact, improved to levels superior to control. It
      is suggested that T3 therapy may be worthy of trial in patients in whom
      reperfusion of the myocardium takes place after a relatively short ischemic
      period (the "stunned myocardium").

PMID- 1985545
TI  - Coronary bypass grafting with totally calcified or acutely dissected ascending
      aorta.
AB  - From August 1984 through November 1988, 10 of 2,658 patients undergoing coronary
      artery bypass grafting had ascending aortic disease that was not amenable to
      proximal anastomoses for coronary bypass grafting. This was due to a calcified
      aorta in 6 and acute aortic dissection in 4. There were 5 male and 5 female
      patients with a mean age of 71 years. Cannulation site was the femoral artery in
      5, ascending aorta in 3, and aortic arch in 2. Profound hypothermia and
      ventricular fibrillation, with no cross-clamp or cardioplegia, was used in 9
      patients, and circulatory arrest in 1. In 8 patients a single internal mammary
      artery was used as the total inflow with a saphenous vein graft brought off the
      internal mammary artery to one or more distal left-sided coronary vessels.
      Bilateral internal mammary arteries were used in 2 other patients. Operative
      mortality was zero. There was one perioperative myocardial infarction and one
      transient stroke without sequelae. All patients have done well from 1 to 6 years
      postoperatively. These data support the use of internal mammary arteries as
      single or bilateral proximal conduits for other venoarterial bypass grafts when
      the aorta is extensively diseased either by calcification or dissection.

PMID- 1985546
TI  - Metabolism of the heart and brain during hypothermic cardiopulmonary bypass.
AB  - The alterations in tissue metabolism induced by hypothermic cardiopulmonary
      bypass are not completely known. Phosphorus-31 nuclear magnetic resonance
      spectroscopy was used to determine the effect of hypothermic cardiopulmonary
      bypass on energy states and intracellular pH of the heart and brain. Sheep were
      instrumented for cardiopulmonary bypass and had a radiofrequency coil placed over
      either the heart or skull. The animals were placed in a 4.7-T magnet at 37
      degrees C and spectra obtained. The animals were cooled on cardiopulmonary bypass
      to either 26 degrees C (n = 17) or 18 degrees C (n = 14) for brain studies and to
      26 degrees C (n = 12) for heart studies. Hypothermia increased the
      phosphocreatine/adenosine triphosphate ratio in the heart (2.38 +/- 0.23 versus
      3.18 +/- 0.37, 37 degrees versus 26 degrees C, respectively, p = 0.03). The brain
      phosphocreatine/adenosine triphosphate ratio increased from 1.70 +/- 0.09 at 37
      degrees C to 2.00 +/- 0.12 at 26 degrees C (p = 0.009) and 2.10 +/- 0.07 at 18
      degrees C (p = 0.0001). Intracellular pH increased during hypothermia (heart:
      7.05 +/- 0.02 to 7.18 +/- 0.02, 37 degrees versus 26 degrees C, p = 0.0001; and
      brain: 7.07 +/- 0.02 versus 7.32 +/- 0.02, 37 degrees versus 18 degrees C, p =
      0.0001). The adenosine triphosphate resonance position is known to be sensitive
      to magnesium binding as well as temperature and was shifted upfield (p less than
      0.01) in both the heart and brain. This effect could be totally explained by the
      temperature dependence of this process.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1985547
TI  - Rupture of a benign mediastinal teratoma into the right pleural cavity.
AB  - A 27-year-old woman with a ruptured mediastinal cystic teratoma had high levels
      of amylase and carcinoembryonic antigen in cystic fluid. The activity of the
      amylase is thought to be the most likely cause of the rupture. High levels of
      carcinoembryonic antigen in pleural fluid are not necessarily indicative of a
      malignant lesion but may suggest the presence of a ruptured teratoma in patients
      with mediastinal tumors.

PMID- 1985548
TI  - Penetrating trauma involving the innominate artery.
AB  - Penetrating trauma involving the innominate artery is uncommon. Few surgeons have
      experience with this injury. A successfully managed case of penetrating
      innominate artery trauma is summarized and the literature reviewed.

PMID- 1985549
TI  - Tricuspid valve papillary fibroelastoma: echocardiographic characterization.
AB  - We report a tricuspid valve papillary fibroelastoma initially detected by
      transthoracic two-dimensional echocardiography and subsequently characterized by
      transesophageal two-dimensional echocardiography. The mass was excised during
      open heart operation, and the diagnosis was verified grossly and
      histopathologically. Transesophageal echocardiography usually provides images far
      superior to those from transthoracic echocardiography and may be a useful adjunct
      for intraoperative localization of intracardiac tumors for excision.

PMID- 1985550
TI  - Surgical repair of Wolff-Parkinson-White syndrome complicated with myocardial
      bridging.
AB  - Myocardial bridging causes myocardial ischemia during supraventricular
      tachycardia. We present a case of Wolff-Parkinson-White syndrome combined with
      myocardial bridging. The patient complained of angina pectoris during paroxysmal
      supraventricular tachycardia because of severe constriction of the left anterior
      descending coronary artery during systole. A myocardial scintigram revealed
      myocardial ischemia in the anteroseptal wall during paroxysmal supraventricular
      tachycardia. Myotomy to prevent myocardial bridging and interruption of the
      accessory conduction pathway was successfully accomplished in a one-stage
      operation.

PMID- 1985551
TI  - Arterial switch procedure in an adult.
AB  - The arterial switch procedure has been shown to offer both anatomic and
      physiologic correction in infants and children with transposition of the great
      arteries and ventricular septal defect. We believe that adults may also benefit
      in some circumstances, as evidenced by the case of a 22-year-old man who
      underwent successful operation after having initially undergone pulmonary artery
      banding for transposition with ventricular septal defect in 1967 when he was 5
      months of age.

PMID- 1985552
TI  - Ascites after rupture of dissecting aortic aneurysm into the right atrium.
AB  - We report successful repair of an aneurysmal aorta-right atrial fistula causing
      intractable ascites. The clamped "ascending aorta" was drained for mixed return
      after perfusion through the femoral vessels and opened during hypothermic arrest.
      Return cannulation through the fistula permitted definitive repair.

PMID- 1985553
TI  - New surgical approach to complicated gastroesophageal reflux disease:
      transthoracic parietal cell vagotomy.
AB  - Surgical treatment of peptic stricture of the esophagus associated with columnar
      (Barrett) metaplasia can be a difficult problem. Collis-Nissen fundoplication
      restores an intraabdominal antireflux barrier for most cases of peptic stricture;
      however, 20% of patients may have persistence of pathological acid reflux. By
      reducing acidity of postoperative reflux, parietal cell vagotomy may complement
      nonresectional surgical results for Barrett stricture.

PMID- 1985554
TI  - Left ventricular aneurysm secondary to Behcet's disease.
AB  - A 16-year-old boy with Behcet's disease who was seen with thrombophlebitis of the
      leg was found to have coronary artery occlusion with postinfarction left
      ventricular aneurysm. Recurrent femoral artery aneurysms and orogenital
      ulceration developed in him. The diagnostic features together with successful
      treatment of this patient and a discussion of Behcet's syndrome are presented.

PMID- 1985555
TI  - Rectus abdominis muscle flap with microvascular anastomoses for repair of
      recurrent sarcoma.
AB  - After radical resection of a recurrent leiomyosarcoma, the thoracic wall was
      stabilized with a Gore-Tex graft. The skin and soft tissue defect was repaired
      with a large rectus abdominis flap in which the circulation was secured by end-to
      end microvascular anastomosis of the inferior epigastric artery to the internal
      mammary artery, which had to be cut during tumor removal.

PMID- 1985556
TI  - Continuous retrograde blood cardioplegia.
AB  - We present a technique of myocardial protection using retrograde cold blood
      cardioplegia. This safe and simple method allows excellent continuous and
      homogeneous cooling of the heart during the ischemic period in all types of open
      heart operations.

PMID- 1985557
TI  - Pleural anesthetics given through an epidural catheter secured inside a chest
      tube.
AB  - Pain management after thoracic surgical procedures is a difficult clinical
      problem. A variety of pain management methods are used with variable efficacy.
      This paper presents an effective method of pleural anesthetic administration
      using a pleural catheter inserted through a chest tube.

PMID- 1985558
TI  - Intraoperative coronary angiography using fluorescein.
AB  - Intraoperative coronary angiography using fluorescein was applied to evaluate the
      patency of saphenous vein grafts just after completion of the distal anastomosis.
      By this technique, the area of the revascularized myocardium was well estimated
      in real time. This intraoperative direct-vision examination gives us more timely
      and precise information during coronary artery bypass grafting.

PMID- 1985559
TI  - Alternative technique for repair of sinus venosus atrial septal defect.
AB  - A technique is described for closure of a sinus venosus atrial septal defect
      using a single patch held in place by sutures placed from outside the right
      atrium and underneath the superior vena cava. The superior vena cava does not
      require enlargement and potential damage to the artery to the sinoatrial node is
      avoided.

PMID- 1985560
TI  - Christiaan Barnard's contribution to the surgical treatment of Ebstein's
      malformation. 1963.

PMID- 1985562
TI  - Empyema and bronchopleural fistula.

PMID- 1985561
TI  - Thymoma: results of 241 operated cases.
AB  - Clinical and histopathological aspects of 241 thymomas were reviewed. One hundred
      sixty of the patients with thymoma had myasthenia gravis and 15 had other
      autoimmune diseases; 55% of the thymomas were encapsulated and 45% invasive.
      Operation was radical resection in 87.5% of the patients, subtotal resection with
      residual tumor in 8.7%, and simple biopsy in 3.7%. A tumor relapse was observed
      in 24 patients (10%): 2 (1.5%) of 133 with encapsulated thymomas and 22 (20.4%)
      of 108 with invasive thymomas; among these patients, a relapse was found in 20.6%
      of the patients who received radiotherapy postoperatively and in 24.6% who did
      not. Adverse prognostic factors were clinical stage IVa (multiple pleural nodes),
      not feasible resection (for technical reasons), inoperable tumor relapse, and
      association with one of the following autoimmune diseases: pure red cell aplasia,
      hypogammaglobulinemia, and lupus erythematosus. Conversely, myasthenia gravis is
      now a curable disease; it contributes to early discovery of associated thymoma,
      thus allowing a better survival for patients with thymoma who have myasthenia
      gravis compared with patients with thymoma but without myasthenia gravis (p less
      than 0.05). Postoperative radiotherapy does not seem necessary after removal of
      encapsulated thymomas, but it is advisable in case of invasive thymomas,
      regardless of the extent of the resection.

PMID- 1985563
TI  - Double outlet left ventricle--long survival after surgical correction.

PMID- 1985564
TI  - Mitral valve reoperation.

PMID- 1985565
TI  - Early restenosis after extended end-to-end anastomosis at neonatal age.

PMID- 1985567
TI  - Symposium on thoracic surgical oncology.

PMID- 1985566
TI  - Esophagogastrectomy via left thoracotomy.

PMID- 1985568
TI  - Valve replacement in patients with endocarditis and cerebral septic emboli.
AB  - Cerebral septic emboli complicate the cases in 20% to 40% of patients with left
      sided endocarditis but the management of these patients who require a valvar
      operation remains unclear. From 1980 to 1988, the incidence of cerebral septic
      embolus was 42% (n = 45) among 106 patients with endocarditis who underwent valve
      replacement at the University of Illinois Hospital in Chicago. Of these 45
      patients, 69% (n = 31) had symptomatic cerebral septic infarctions and 31% (n =
      14) were asymptomatic. Findings on cerebral computed tomographic scans included
      ischemic infarcts (n = 36, 80%), hemorrhagic infarcts (n = 5, 11%), normal
      studies (n = 2, 4%), and unknown (n = 2, 4%). Neurological complications after
      valve replacement included postoperative strokes (n = 6, 6%), cerebral abscesses
      (n = 2, 2%), and seizure (n = 1, 1%). The presence of a hemorrhagic infarct
      preoperatively predisposed to a perioperative stroke (p less than 0.05). In
      conclusion, cerebral septic infarctions, both symptomatic and asymptomatic, are
      common among patients with endocarditis referred for valvar operation. In the
      absence of a hemorrhagic infarct, valve replacement can be performed with minimal
      risk of a perioperative stroke.

PMID- 1985569
TI  - Tracheoesophageal anastomosis for intractable aspiration pneumonia.
AB  - Permanent tracheostomy and tracheoesophageal anastomosis were performed as a
      means of surgical intervention for the treatment of intractable aspiration
      pneumonia. Conventional methods of tracheoesophageal anastomosis have entailed
      various problems. The improved method devised by us uses the special histological
      features and enables safe and reliable anastomosis. By this method, the tracheal
      perichondrium is retained and the strength of the anastomosed portion of the
      trachea is maintained, the failure of sutures due to tension on the anastomotic
      site being prevented. Also, reanastomosis can be performed after the cure of
      primary disease.

PMID- 1985570
TI  - Intrathoracic Nissen fundoplication: long-term clinical and pH-monitoring
      evaluation.
AB  - From 1976 until April 1989, 31 intrathoracic total fundoplications were performed
      for reflux esophagitis and irreducible hiatus hernia. In the first 16 patients
      (group 1) the operation was complicated with acute perforation of the wrap in 4
      cases, bronchogastric fistula in 1, and herniation of the wrap higher in the
      chest in 1. Technical modifications were applied to 15 more recent patients
      (group 2). These are enlargement of the hiatus, looseness of the wrap and its
      appropriate anchorage, avoidance of forceps when handling the stomach, care with
      the vagi, and efficient gastric decompression in the postoperative period. The
      postoperative course was always uneventful in group 2. Twenty-six patients, who
      still have their initial wrap, were considered for clinical evaluation: 11 from
      group 1 (mean follow-up, 81.5 months) and 15 from group 2 (mean follow-up, 32.8
      months). All are free from any symptom of reflux; gas-bloat syndrome is
      infrequent and dysphagia is relieved. Twenty-four-hour pH monitoring, performed
      in 14 patients (3 from group 1 and 11 from group 2) (mean follow-up, 42 months),
      was normal in 13; a pathological upright reflux (time pH less than 4, 8.4%) was
      demonstrated in one symptom-free woman in whom endoscopy was unremarkable.
      Mechanisms of complications experienced in group 1 are analyzed in the light of
      the technical evolution of the procedure, and the place of the intrathoracic
      total fundoplication in the management of short esophagus is defined, considering
      the other available surgical techniques.

PMID- 1985571
TI  - Empyema thoracis: 14-year experience in a teaching center.
AB  - One hundred two patients with empyema thoracis were managed at the Royal
      Melbourne Hospital between 1976 and 1989. Fifty-five cases of empyema thoracis
      were postpneumonic, 8 followed esophageal rupture, and 5 were associated with
      thoracic trauma. Some form of systemic illness was a major contributing factor in
      the presentation of 29 patients. A single causal organism was found in 53
      patients (the most common being Staphylococcus aureus), multiple organisms in 36,
      and no growth in 13. During the years 1983 to 1989 there was an increased
      incidence of empyemas caused by multiple or antibiotic-resistant organisms.
      Operative drainage was required in 90 patients and 12 were managed by
      thoracentesis or intercostal tube drainage alone. The in-hospital mortality rate
      for patients managed nonoperatively was 58% (7 of 12 patients); it was 16% (14 of
      90 patients) for those receiving operative drainage. There were seven late
      deaths, four empyema related and three nonrelated. Early adequate operative
      drainage is recommended for patients with empyema thoracis.

PMID- 1985572
TI  - Mechanical circulatory assistance after heart transplantation.
AB  - From October 1985 through December 1989, 92 heart transplant procedures were
      performed in 89 patients. Nine patients (aged 19 to 66 years; 7 male, 2 female)
      required mechanical circulatory support after transplantation because of primary
      idiopathic organ failure (n = 2), implant difficulty (2), poor organ quality (2),
      or acute right heart failure (3). Devices used included the intraaortic balloon
      pump (6), centrifugal right ventricular assist device (2), left ventricular
      assist (1), biventricular assists (2), and total artificial heart (1). Two
      patients required multiple devices. One patient underwent retransplantation.
      Implant time ranged from 1 to 18 days. One early death occurred owing to right
      heart failure 6 days after transplantation, 7 hours after removal of a right
      ventricular assist device, for an overall mortality of 11%. The remaining 8
      patients are alive 4 months to 28 months after transplantation. The actuarial 1
      year survival of 89% +/- 10% compares well with the survival of 87% +/- 4% for
      the entire transplant group. All surviving patients are in functional class I.
      Echocardiographic examination in all patients revealed left ventricular ejection
      fraction to be normal in 7 and depressed in 1. Extending the criteria for organ
      donors or difficulty with the implant procedure can lead to early organ failure,
      which may be reversible with circulatory assistance allowing excellent survival.

PMID- 1985574
TI  - Triiodothyronine: to be or not to be, that is the question.

PMID- 1985573
TI  - Multiple primary bronchogenic carcinomas: treatment and follow-up.
AB  - A second primary bronchogenic carcinoma subsequently developed 8 to 156 months
      later in 19 patients who underwent curative resection of primary bronchogenic
      carcinomas. The second primary tumor was treated by surgical resection in 9
      patients, 3 patients' tumors were considered unresectable, and the remaining 7
      patients, despite having potentially resectable tumors, did not undergo resection
      because of insufficient pulmonary reserve or unwillingness to undergo resection.
      Actuarial life-table analysis of survival for the 9 patients who underwent
      resection showed a median survival time of 110.3 months compared with 19 months
      for the group with unresected but resectable tumors and 10.5 months for the group
      with unresectable tumors. There was no operative mortality in the group with
      resected tumors. We conclude that in patients in whom a second primary carcinoma
      of the lung develops, surgical resection prolongs survival and can be performed
      with a low operative mortality.

PMID- 1985575
TI  - Hemodynamics versus biopsy findings during cardiac transplant rejection.
AB  - Before the use of cyclosporine as the major component for immunosuppression after
      cardiac transplantation, rejection was accompanied by catastrophic hemodynamic
      decompensation. However, the hemodynamic changes that occur during rejection
      after cardiac transplantation in patients treated with cyclosporine have not been
      clearly described. Between July 1986 and October 1989, 89 adults underwent
      orthotopic heart transplantation at the University of Michigan Medical Center.
      All patients received triple-drug therapy immunosuppression consisting of
      steroids, cyclosporine, and azathioprine. Cardiac hemodynamics were measured and
      correlated with the histologic assessment of rejection. There have been ten
      deaths among these 89 patients for an overall survival of 89%. There were no
      deaths from rejection. One hundred fifty-three of the biopsy specimens were read
      as grade 0, 31 were grade 1, 75 were grade 2, 103 were grade 3, and 9 patients
      had grade 4 biopsy specimens. No hemodynamic differences were noted in patients
      with increasing grade of rejection. Five patients (5/9, 55%) with severe
      rejection (grade 4) had symptoms of congestive heart failure at the time of
      biopsy. These symptomatic grade 4 patients differed from asymptomatic grade 4
      patients only in cardiac output (2.9 versus 5.2 L/min). Overall hemodynamic
      decompensation was not evident as rejection grade increased. Routine serial
      endomyocardial biopsies remain the procedure of choice in the diagnosis of
      rejection in the asymptomatic patient after cardiac transplantation as
      hemodynamics do not predict degree of rejection.

PMID- 1985576
TI  - Delayed chest wall pain due to sternal wire sutures.
AB  - This report describes 18 patients with disabling chest wall pain due to one or
      more sternal wire sutures. The pain occurred from 2 to 84 months after a median
      sternotomy. The pain was described either as sharp and stabbing or as a deep
      seated ache. The involved wires had an exaggerated fibrous tissue reaction
      surrounding the twisted portion. The adjacent noninvolved wires had minimal
      reaction. In the last 7 patients, serial sections of the fibrous tissue revealed
      entrapment of one or more sensory nerve fibers. In 6 of the 7 electrical
      potentials were measured and found to be elevated, indicating wire damage during
      twisting. Ferroxyl tests confirmed the collection of iron ions at this anodic
      point as a result of corrosion. Removal of the involved wires and the fibrous
      tissue surrounding this anodic point relieved the symptoms of pain and tenderness
      resulting from entrapped sensory nerves.

PMID- 1985577
TI  - Art and science in the management of endocarditis.

PMID- 1985578
TI  - Comparison of supraannular and subannular pledgeted sutures in mitral valve
      replacement.
AB  - Ten fresh canine hearts were used to compare the peak left ventricular pressure
      required to disrupt prosthetic mitral valves sutured in place with horizontal
      mattress sutures with either subannular or supraannular pledgets. Each group
      consisted of 5 animals. A 29-mm Medtronic mitral valve was secured in the mitral
      position with ten pledgeted sutures. The aorta was cannulated and normal saline
      solution was infused into the left ventricle until valvar disruption occurred.
      The peak pressure and the location and mechanism of disruption were then noted.
      At the peak left ventricular pressure required for valvar disruption, no
      individual sutures were broken. Instead, in all specimens a subannular myocardial
      rupture occurred in the posterior portion of the mitral annulus along the extent
      of the atrioventricular groove. In addition, the posterior wall of the left
      atrium dissected upward subsequently. Significantly greater pressures were
      required in the group with subannular suture placement as compared with the
      supraannular group (354 +/- 37 versus 236 +/- 33 mm Hg; p less than 0.0007).
      These data suggest that placement of horizontal mattress sutures with pledgets in
      the subannular position is superior to the currently recommended method of
      supraannular suture placement in mechanical valves.

PMID- 1985579
TI  - Staged repair of pulmonary atresia with ventricular septal defect and major
      systemic to pulmonary artery collaterals.
AB  - Fifty-eight consecutive patients with pulmonary atresia, ventricular septal
      defect, hypoplastic pulmonary arteries with arborization defects, and major
      aortopulmonary collaterals were entered into a program for staged surgical repair
      between January 1979 and July 1989. Prerepair preparatory procedures were
      designed to (1) encourage native pulmonary artery growth by increasing blood flow
      and (2) unifocalize pulmonary blood supply by transplanting or ligating major
      collaterals. A total of 121 staging procedures were performed with an overall
      mortality of 10.3%. One hundred thirty-four major collaterals were either ligated
      or transplanted. Thirty patients eventually underwent hemodynamic repair with an
      early mortality of 3.3% and late mortality of 10.0%. Twenty-six current survivors
      of repair remain clinically well after a mean follow-up of 3.6 years. Ten
      patients are currently in various stages of preparation. Twelve patients (20.7%)
      failed to achieve minimum requirements for repair after staging and await further
      palliation or heart-lung transplantation. The principles of management have
      evolved over the years and are discussed.

PMID- 1985580
TI  - Altered cellular immune function in the atelectatic lung.
AB  - Pulmonary atelectasis is common and may predispose the lung to infection. We have
      previously shown that atelectasis impairs alveolar macrophage antibacterial
      function. This study examines the effect of atelectasis on the cytotoxic function
      of lymphocytes harvested from the bronchoalveolar space of atelectatic lung
      segments by bronchoalveolar lavage. Specifically, we studied natural killer and
      lectin-dependent cell-mediated cytotoxicity in peripheral blood and
      bronchoalveolar lavage lymphocytes from the atelectatic lower lobes and
      contralateral normal lobes in a group of 8 dogs. We observed a decline of natural
      killer and lectin-dependent cell-mediated cytotoxicity to 62.7% and 61.5%,
      respectively, of preatelectasis control values in the affected lung lobes (p less
      than 0.01). Simultaneous measurements of cytotoxic activity of bronchoalveolar
      lavage lymphocytes harvested from the unaffected contralateral normal lungs were
      comparable with control values. On the other hand, natural killer and lectin
      dependent cell-mediated cytotoxicity activities in peripheral blood lymphocytes
      were significantly increased in animals having right lower lobe atelectasis
      (166.7% and 154.7% of pretreated normal control, respectively, p less than 0.01).
      Atelectasis was also associated with an influx of polymorphonuclear leukocytes
      into the bronchoalveolar compartment. These findings confirm the presence of
      natural killer cells and cytotoxic lymphocytes in the bronchoalveolar compartment
      and demonstrate an atelectasis-induced impairment of local bronchoalveolar
      lymphocyte function. Such a dysfunction of local lung cellular host defenses may
      render the atelectatic lung susceptible to infection.

PMID- 1985581
TI  - Unifocalization for pulmonary atresia with ventricular septal defect.

PMID- 1985582
TI  - Amiodarone versus bretylium for suppression of reperfusion arrhythmias in dogs.
AB  - Reperfusion arrhythmias are an important complication of interventions to limit
      infarct size. Recently, amiodarone has been shown to be rapidly effective in
      suppressing sustained, incessant ventricular tachycardia and ventricular
      fibrillation in this setting. This study evaluated the time course of arrhythmia
      suppression and comparative efficacy of amiodarone versus bretylium in a canine
      model of reperfusion arrhythmias. Of 23 dogs subjected to a Harris two-stage
      coronary artery ligation followed by release, 18 demonstrated clinically
      significant ventricular arrhythmias and received either intravenous amiodarone, 5
      mg/kg (9 dogs), or intravenous bretylium, 5 mg/kg (9 dogs). Direct-current shocks
      for sustained ventricular tachycardia or ventricular fibrillation were
      administered as necessary. Amiodarone rapidly suppressed sustained ventricular
      tachycardia and ventricular fibrillation in this model with no dog in the
      amiodarone-treated group requiring cardioversion after completion of the 15
      minute infusion versus 4 of 9 dogs in the bretylium-treated group (p less than
      0.05). Amiodarone was more effective than bretylium in suppressing episodes of
      sustained ventricular tachycardia/ventricular fibrillation, episodes of
      nonsustained ventricular tachycardia, and premature ventricular complexes. The
      blood pressure and heart rate decreased more after amiodarone administration than
      after bretylium administration. We conclude that, in the canine reperfusion
      arrhythmia model, amiodarone is rapidly effective in suppressing ventricular
      arrhythmias and is more effective than bretylium.

PMID- 1985583
TI  - Traumatic asphyxia.
AB  - During a 5-year period, we treated 14 cases of traumatic asphyxia. There were 12
      male and 2 female patients ranging in age from 2 to 32 years. Most suffered
      crushing injuries at work or were run over by motor vehicles. Mild to severe
      cervicofacial cyanosis and petechiae developed in all patients. A fear response
      was reported by 12 of the patients. Subconjunctival hemorrhage was also found in
      12 patients. Nine patients had tachypnea and 7 complained of dyspnea. Most of the
      patients suffered some associated injuries including 8 head injuries, 7 pulmonary
      contusions, and 6 cases of blunt abdominal trauma. Less-associated injuries were
      rib fractures, brachial and radial nerve injuries, hemothorax, and pneumothorax.
      The hospital stay ranged from 4 to 28 days (mean, 14 days) and follow-up from 10
      to 60 months (mean, 32 months). Treatment for traumatic asphyxia included
      measurement of arterial blood gases, oxygen supplementation, and intubation with
      mechanical ventilation. The patients' recovery conditions were relative to the
      severity of injury and the associated injuries.

PMID- 1985584
TI  - Might free arterial grafts fail due to spasm?
AB  - The rat femoral artery was used as a free graft and was studied after 2, 7, 14,
      30, and 60 days. The patency of the grafts was 100% (2 days, n = 6), 78% (7 days,
      n = 9), 63% (14 days, n = 8), 33% (30 days, n = 12), and 18% (60 days, n = 11).
      Histology showed an intimal thickening after 14 days and the media, which in the
      controls consisted of eight to ten layers of myocytes, was reduced to six to
      eight cell layers. During the first 2 weeks the graft segments had an impaired
      contraction when exposed to Krebs solution with 124 mmol/L K+, whereas after 1
      month and later the graft segments approached the controls or had even higher
      contractile force. The thromboxane mimic U-46619 elicited full contractile force
      at all times whereas the potency was significantly lower during the first 14
      days. Noradrenaline was unable to induce contraction in the graft segments during
      the first 14 days, but at 30 and 60 days it had regained full contractile force
      and was significantly more potent (approximately 60 times) in the graft segments
      compared with the controls. This study suggests that intimal thickening and
      hypercontractility might be a problem in free muscular arterial grafts.

PMID- 1985585
TI  - Risk stratification of ambulatory patients suspected of Pneumocystis pneumonia.
AB  - To determine whether aspects of clinical history, physical examination, and
      laboratory studies improve the diagnostic accuracy of the chest roentgenogram in
      the diagnosis of Pneumocystis carinii pneumonia (PCP), we followed up 302
      consecutive patients with respiratory symptoms and risk factors for human
      immunodeficiency virus. Of the 279 patients (92%) with follow-up information
      available, 31 (11%) were diagnosed with PCP. Only 68% of patients with PCP had
      typical chest roentgenograms. Regression analysis identified four independent
      predictors of PCP: diffuse or perihilar infiltrates, presence of mouth lesions,
      lactate dehydrogenase level more than 220 U/L, and erythrocyte sedimentation rate
      50 mm/h or more. Using these four predictors, patients could be stratified into
      low-, intermediate-, and high-risk groups for PCP. We suggest that examination of
      the mouth, chest roentgenogram, lactate dehydrogenase level, and erythrocyte
      sedimentation rate be part of the evaluation of ambulatory patients with
      respiratory symptoms at risk for human immunodeficiency virus.

PMID- 1985587
TI  - Primary care patients who refuse specialized mental health services.
AB  - The charts of 65 patients who completed mental health care referrals were
      compared with those of 65 patients who failed to complete such referrals. In the
      year before referral, the noncompliant patients made 37% more medical visits than
      the compliant patients. As compared with the compliant patients, a significantly
      greater proportion of the noncompliant patients' medical visits were for
      difficult-to-explain somatic symptoms. Mental health referrals from some
      physicians were much more successful than referrals from other physicians. By
      attending to their patients' pattern of health care utilization, primary care
      physicians may be able to identify patients at high risk for noncompliance with
      mental health referrals.

PMID- 1985586
TI  - Effect of race on expression of acquired immunodeficiency syndrome-associated
      nephropathy.
AB  - The prevalence of renal disease associated with the acquired immunodeficiency
      syndrome (AIDS) is unknown, but appears to vary in different regions. Centers in
      New York, NY, and Miami, Fla, have reported patients with renal disease
      complicating AIDS. These populations have included large proportions of black
      patients and intravenous drug abusers. Reports from San Francisco, Calif, have
      suggested the prevalence of renal disease complicating AIDS is low, but the
      population was composed primarily of white patients, with a low proportion of
      drug abusers. The George Washington University Medical Center was the site of
      treatment for 31.4% of the patients with AIDS in Washington, DC. This population
      was split roughly evenly between black and white patients. A retrospective survey
      of patients with both AIDS and renal disease revealed approximately two thirds of
      the patients were black, reflecting the demographics of the population with AIDS;
      11% of patients had intravenous drug abuse as a risk factor for the development
      of AIDS; and 74% had acute renal failure. Of these patients, approximately equal
      proportions were black and white. Twenty-six percent of the population had
      chronic renal failure, but the overwhelming proportion were black. There were no
      differences between proportions of patients in age, sex, race, or risk factors in
      patients with acute renal failure and chronic renal failure, but there was a
      significant difference in the proportions of black and white patients with
      chronic renal failure. The reason for these differences is unknown, but
      differences in host responses to viral proteins, physiologic adaptations, or
      socioeconomic factors in these populations may play an important role in
      mediating the expression of renal disease in individual patients.

PMID- 1985588
TI  - Acute rheumatic fever in West Virginia. Not just a disease of children.
AB  - Rheumatic fever is a poststreptococcal disease that is receiving renewed
      attention by the medical community. We describe a recent increase in the number
      of observed cases of acute rheumatic fever (ARF) in West Virginia. This is the
      fifth report of a recent increase in the incidence of ARF in the Ohio Valley area
      in the last 4 years. In contrast to the other reports, nearly two thirds of our
      cases of ARF were in adults, more than half of whom had suffered previous bouts
      of ARF. In these adults with recurrences, none was taking prophylactic penicillin
      at the time of presentation. Carditis was present in seven adults, two without a
      history of carditis. Arthritis was present in all adult patients. These data
      indicate a possible geographic phenomenon related to the increased number of
      observed cases of ARF and document that ARF is not simply a disease of childhood.
      Furthermore, our findings highlight the need for extended penicillin prophylaxis
      for secondary prevention of ARF, especially for those with an increased risk of
      acquiring a streptococcal upper respiratory tract infection.

PMID- 1985589
TI  - Suicide attempts by the old and the very old.
AB  - Attempted suicide by the elderly is a major psychiatric problem. Ninety-five
      patients between 60 and 90 years of age were evaluated by a psychiatric
      consultation service after a suicide attempt. Characteristics of this group
      included (1) a high degree of premeditation, (2) a tendency toward firearm use
      and wounds to the head, (3) male sex, (4) coexisting medical problems, (5)
      serious intent that increased by decade, (6) solitary living arrangements, (7)
      presence or history of a major psychiatric illness, and (8) ill health reported
      as a precipitant to suicidality. Major depression was the most common psychiatric
      diagnosis, with congestive heart failure and chronic obstructive pulmonary
      disease the most frequently noted physical ailments. This elderly population of
      attempters resembled older persons who actually completed suicide and differed
      significantly from 1630 persons aged 16 to 59 years who attempted suicide.
      Heightened investigation of depressive features, treatment of alcohol abuse,
      early referral for psychiatric care, limited access to firearms, and strategies
      aimed at decreasing social isolation are recommended to decrease the likelihood
      of completed suicide in the elderly.

PMID- 1985590
TI  - Treatment of flexor tenosynovitis of the hand ('trigger finger') with
      corticosteroids. A prospective study of the response to local injection.
AB  - We developed a protocol to maximize medical therapy for "trigger finger." Fifty
      eight patients with 77 episodes of flexor tenosynovitis of the hand that was
      resistant to rest, therapy with nonsteroidal anti-inflammatory drugs, and/or
      splinting were treated with single or multiple injections of depo
      methylprednisolone acetate or triamcinolone acetonide. Patients were
      prospectively followed up for an average of 4.6 years. Results showed that
      symptoms and signs resolved in 61% after a single injection. Recurrent episodes,
      after prolonged pain-free intervals, occurred in 27% and were effectively re
      treated with injection. In 12% of cases, either injection failed or early
      recurrence required surgical release. Local adverse reactions to injection,
      including pain at the injection site, stiffness, ecchymosis, or atrophy of
      subcutaneous fat, were self-limited. No episodes of postinjection infection or
      tendon rupture occurred. The medical management of flexor tenosynovitis with
      local corticosteroid injection(s) is effective in nearly 90% of cases and is free
      from serious adverse reactions.

PMID- 1985591
TI  - Low serum thyrotropin (thyroid-stimulating hormone) in older persons without
      hyperthyroidism.
AB  - We studied a large population (n = 2575) of unselected ambulatory persons older
      than 60 years to determine the prevalence of a low serum thyroid-stimulating
      hormone (TSH) level, ie, of less than 0.1 mU/L using a sensitive assay, a level
      suggestive of hyperthyroidism in younger adults. One hundred one persons (3.9%)
      had a low serum TSH level. About half of them (51/101) were taking thyroid
      hormone. Of the remainder, 44 were not hyperthyroid did not become so during up
      to 4 years of follow-up. Forty-one of the 44 euthyroid persons had a serum
      thyroxine level of less than 129 nmol/L; repeated testing showed a serum TSH
      level of more than 0.1 mU/L in the three euthyroid persons with a serum thyroxine
      level of more than 129 nmol/L. Only six were hyperthyroid or became so during the
      follow-up period; all had a serum thyroxine level of more than 129 nmol/L.
      Routine clinical examination was not a sensitive indicator of hyperthyroidism and
      did not permit discrimination from euthyroidism. A low value of serum TSH alone,
      while it had high sensitivity and specificity for hyperthyroidism, had a low
      positive predictive value (12%) for this diagnosis; addition of the thyroxine
      assay raised the predictive value fivefold to 67%. A low value of serum TSH is
      far more common in older persons than is hyperthyroidism. Low values in euthyroid
      persons are accompanied by a clearly normal serum T4 concentration (less than 129
      nmol/L) or by a serum TSH level of more than 0.1 mU/L on repeated testing. We
      recommend measurement of the serum TSH thyroid concentration, using a sensitive
      assay, as the initial step in testing any older person for possible
      hyperthyroidism. Measurement of the serum T4 concentration or the free T4 index
      on the same sample would be needed only in the approximately 2% with a serum TSH
      level of less than 0.1 mU/L; alternatively, the TSH assay in these could be
      repeated at a later time.

PMID- 1985593
TI  - Hemoptysis. Indications for bronchoscopy.
AB  - Indications for bronchoscopy in patients with hemoptysis and a normal or
      nonlocalizing chest roentgenogram continue to be controversial. We reviewed the
      records for 119 bronchoscopies performed for hemoptysis in patients with a normal
      (n = 75) or nonlocalizing (n = 44) chest roentgenogram. Bronchogenic carcinoma
      was identified in 2.5% of the bronchoscopies. Additional neoplasms were found in
      another 2.5%. The presence of nonlocalizing abnormalities was not associated with
      an increase in either the rate of bronchogenic carcinoma or in the diagnostic
      yield (specific anatomic diagnosis or bleeding site identified) at bronchoscopy
      when compared with patients with normal chest roentgenograms. The factors of male
      sex, age more than 40 years, and a more than 40 pack-year smoking history appear
      useful in identifying patients in whom the yield of bronchoscopy is likely to be
      high.

PMID- 1985592
TI  - Estrogens and disease prevention.

PMID- 1985594
TI  - Gonococcal osteomyelitis. Case report and review of the literature.
AB  - We report the 11th case of gonococcal osteomyelitis in the postantibiotic era.
      This case demonstrates the classic presentation of osteomyelitis associated with
      gonorrhea, a subacute illness with minimal systemic symptoms. In addition, we
      present radiologic evidence of the pathogenesis of this unusual osteomyelitis
      from a contiguous joint infection.

PMID- 1985595
TI  - Spontaneous remission in Cushing's disease.
AB  - Four patients with proved Cushing's disease underwent spontaneous clinical and
      biochemical remission. They were part of an 11-patient group treated with methods
      that allowed spontaneous remission to be observed. Each patient was treated
      differently, one each with metyrapone tartrate, ketoconazole, bilateral
      adrenalectomy and adrenal autotransplantation, and no treatment. Spontaneous
      remission occurred 9 months to 5 years after diagnosis as evidenced by
      restoration of normal adrenal function occurring symptomatically in two patients
      and advent to hypoadrenalism with addisonian crisis in the two others. We
      conclude that spontaneous remission in Cushing's disease may not be a rare
      entity, although its actual incidence has yet to be established.

PMID- 1985596
TI  - Screening mammography in clinical practice. A complex activity.

PMID- 1985597
TI  - Nontyphoidal Salmonella pleuropulmonary infections.

PMID- 1985598
TI  - Cocaine abuse by medical students.

PMID- 1985599
TI  - Practical utility of lactate dehydrogenase in the diagnosis of human
      immunodeficiency virus-related Pneumocystis carinii pneumonia.

PMID- 1985600
TI  - Complications associated with thoracentesis.

PMID- 1985601
TI  - Importance of complete cytometric evaluation of vesical dysfunction in elderly
      diabetic patients.

PMID- 1985602
TI  - Ranitidine-induced thrombocytopenia.

PMID- 1985603
TI  - Rapid correction of hypokalemia: a note of caution.

PMID- 1985604
TI  - Hospital nonsmoking policies.

PMID- 1985605
TI  - Detection and treatment of elevated blood cholesterol. What have we learned?

PMID- 1985606
TI  - The achievement of clean air health care. Is it appropriate? Is it feasible?

PMID- 1985607
TI  - Alcohol and the heart. The long-term effects of alcohol on the cardiovascular
      system.

PMID- 1985608
TI  - Expanded Clinical Evaluation of Lovastatin (EXCEL) study results. I. Efficacy in
      modifying plasma lipoproteins and adverse event profile in 8245 patients with
      moderate hypercholesterolemia.
AB  - In the Expanded Clinical Evaluation of Lovastatin (EXCEL) Study, a multicenter,
      double-blind, diet- and placebo-controlled trial, we evaluated the efficacy and
      safety of lovastatin in 8245 patients with moderate hypercholesterolemia.
      Patients were randomly assigned to receive placebo or lovastatin at a dosage of
      20 mg once daily, 40 mg once daily, 20 mg twice daily, or 40 mg twice daily for
      48 weeks. Lovastatin produced sustained, dose-related (P less than .001) changes
      as follows (for dosages of 20 to 80 mg/d): decreased low-density lipoprotein
      cholesterol level (24% to 40%), increased high-density lipoprotein-cholesterol
      level (6.6% to 9.5%), decreased total cholesterol level (17% to 29%), and
      decreased triglyceride level (10% to 19%). The National Cholesterol Education
      Program's low-density lipoprotein-cholesterol level goal of less than 4.14 mmol/L
      (160 mg/dL) was achieved by 80% to 96% of patients, while the less than 3.36
      mmol/L (130 mg/dL) goal was achieved by 38% to 83% of patients. The difference
      between lovastatin and placebo in the incidence of clinical adverse experiences
      requiring discontinuation was small, ranging from 1.2% at 20 mg twice daily to
      1.9% at 80 mg/d. Successive transaminase level elevations greater than three
      times the upper limit of normal were observed in 0.1% of patients receiving
      placebo and 20 mg/d of lovastatin, increasing to 0.9% in those receiving 40 mg/d
      and 1.5% in those receiving 80 mg/d of lovastatin (P less than .001 for trend).
      Myopathy, defined as muscle symptoms with a creatine kinase elevation greater
      than 10 times the upper limit of normal, was found in only one patient (0.1%)
      receiving 40 mg once daily and four patients (0.2%) receiving 80 mg/d of
      lovastatin. Thus, lovastatin, when added after an adequate trial of a prudent
      diet, is a highly effective and generally well-tolerated treatment for patients
      with moderate hypercholesterolemia.

PMID- 1985609
TI  - The impact of physician compliance on screening mammography for older women.
AB  - Screening mammography is underutilized, even for women older than 50 years for
      whom there is a general consensus that regular annual screening is appropriate
      and necessary. To evaluate reasons for this underutilization, we studied a random
      sample of 517 women in Los Angeles, Calif who were older than 50 years. All women
      were found to be underscreened, especially women older than 65 years. For
      example, approximately 35% of women 50 to 64 years old and 47% of women aged 65
      years and older never had had even one mammogram. Analyses revealed that the most
      important factor that predicted whether a women ever had had a mammogram was
      whether her physician had talked to her about mammography. Women were between
      four and 12 times more likely, depending on their age group, to have had a
      mammogram at some time if their physicians discussed it with them. The
      discussions did not need to be lengthy or complex. These results indicate that
      physicians need to know that discussing screening mammography with their patients
      has a major impact on breast cancer screening behaviors.

PMID- 1985610
TI  - The relationship of Papanicolaou testing and contacts with the medical care
      system to stage at diagnosis of cervical cancer.
AB  - The relationship of Papanicolaou (Pap) testing and physician visits to stage at
      diagnosis of cervical cancer was assessed by interviews with 149 women with
      invasive cervical cancer and 214 women with in situ cervical cancer. A
      significantly smaller percent of study subjects with invasive disease than in
      situ disease had at least one Pap test in the 3 years prior to diagnosis (age-
      and race-adjusted odds ratio: 3.38). The two groups did not differ in visits to a
      physician for other reasons during this period. Pap testing decreased with
      increasing age for both groups, but not physician visits. While 65% percent of
      the subjects with invasive disease aged between 65 and 79 years had never had a
      Pap test until diagnosis, 88% had seen a physician in the preceding 3 years.
      Women with regional or distant invasive disease were least likely to have had Pap
      tests, and, within this group, those aged between 35 and 64 years were also least
      likely to have seen a physician. Strategies for early detection must reflect
      missed opportunities and the need to bring those not receiving care into the
      system.

PMID- 1985611
TI  - Decreased mortality in users of estrogen replacement therapy.
AB  - In a prospective study of 8881 postmenopausal female residents of a retirement
      community in southern California, we evaluated in detail the relationship between
      estrogen use and overall mortality. After 7 1/2 years of follow-up, there had
      been 1447 deaths. Women with a history of estrogen use had 20% lower age
      adjusted, all-cause mortality than lifetime nonusers (95% confidence interval,
      0.70 to 0.87). Mortality decreased with increasing duration of use and was lower
      among current users than among women who used estrogens only in the distant past.
      Current users with more than 15 years of estrogen use had a 40% reduction in
      their overall mortality. Among oral estrogen users, relative risks of death could
      not be distinguished by specific dosages of the oral estrogen taken for the
      longest time. Women who had used estrogen replacement therapy had a reduced
      mortality from all categories of acute and chronic arteriosclerotic disease and
      cerebrovascular disease. This group of women had a reduced mortality from cancer,
      although this reduction was not statistically significant. The mortality from all
      remaining causes combined was the same in estrogen users and lifetime nonusers.

PMID- 1985612
TI  - The relationship between hypochondriasis and medical illness.
AB  - Forty-one Diagnostic and Statistical Manual of Mental Disorders-III-Revised
      hypochondriacs were accrued from a primary care practice. Seventy-five control
      subjects were selected at random from among the remainder of the patients in the
      same clinic. All subjects completed a structured diagnostic interview and
      standardized self-report questionnaires. Medical morbidity was assessed with a
      medical record audit and with primary physicians' ratings. The hypochondriacal
      and comparison samples did not differ in aggregate medical morbidity, although
      the hypochondriacal sample had more undiagnosed complaints and nonspecific
      findings in their medical records. Within the comparison sample, higher levels of
      medical morbidity were associated with higher levels of hypochondriacal symptoms.
      This occurred primarily because the most serious medical disorders were
      associated with more bodily preoccupation, disease conviction, and somatization.
      Within the hypochondriacal sample, no correlation was found between the degree of
      hypochondriasis and the extent of medical morbidity.

PMID- 1985613
TI  - Preoperative aspirin therapy and reoperation for bleeding after coronary artery
      bypass surgery.
AB  - We performed a case-control study to estimate the relative risk of reoperation
      for bleeding in coronary artery bypass graft patients who had taken aspirin
      within the 7 days preceding surgery. Comparison of 90 cases of reoperation with
      180 matched control subjects gave an estimated odds ratio for reoperation of 1.82
      (95% confidence interval, 1.23 to 3.32). Although their preoperative coagulation
      values were similar, cases used significantly more whole blood (cases, 9.5 +/-
      5.2 units; control subjects, 3.0 +/- 2.0 units; median +/- interquartile range),
      packed red blood cells (cases, 2.1 +/- 4.0 units; control subjects, 0.9 +/- 2.0
      units), and platelets (cases, 12.2 +/- 12.0 units; control subjects, 2.9 +/- 4.0
      units) than control subjects. Cases had intensive care unit stays of 4.7 +/- 5.7
      days (mean +/- SD) vs 2.1 +/- 1.9 days for control subjects and postoperative
      hospitalizations of 10.9 +/- 8.2 days vs 7.0 +/- 3.2 days for control subjects.
      We conclude that aspirin exposure within 7 days before coronary bypass surgery is
      associated with an increased rate of reoperation for bleeding and that
      reoperation is associated with large increases in transfusion requirements and
      intensive care unit and hospital stays.

PMID- 1985615
TI  - Walter J. Zeiter lecture. Graduate medical education: does form follow function?

PMID- 1985614
TI  - Weight gain at the time of menopause.
AB  - We studied prospectively the weight change and the effect of weight change on
      changes in coronary heart disease risk factors in a population-based sample of
      485 middle-aged women. All women were studied first in 1983 to 1984, when they
      were premenopausal and aged 42 to 50 years, and then restudied in 1987. Women
      gained an average of 2.25 +/- 4.19 kg during this 3-year period; 20% of women
      gained 4.5 kg or more, and only 3% lost 4.5 kg or more. There were no significant
      differences in weight gain of women who remained premenopausal and those who had
      a natural menopause (+2.07 kg vs +1.35 kg). Weight gain was significantly
      associated with increases in blood pressure and levels of total cholesterol, low
      density lipoprotein cholesterol, triglycerides, and fasting insulin. Weight gain
      is thus a common occurrence for women at the time of menopause and is related to
      the changes in coronary heart disease risk factors observed during this period.
      Efforts to lose weight or to prevent weight gain may help to mitigate the
      worsening in coronary heart disease risk factors in middle-aged women.

PMID- 1985616
TI  - Muscle conditioning in late poliomyelitis.
AB  - To study the adaptability of postpolio muscles, 12 subjects (mean age 54 years)
      participated in a high-intensity resistance exercise program. Seventy-five
      percent met the criteria for postpolio syndrome. Isometric and isokinetic
      strength and muscle endurance were measured. Polio-affected muscles were
      identified in muscle biopsies. The biopsies were also used for measurements of
      enzymatic activities and for histochemical and histopathologic analyses.
      Pretraining strength values were less than half those of healthy controls, mean
      fiber areas were twice those of healthy controls, and oxidative enzyme activity
      was low. After training, a significant increase in isometric (mean 29%) and
      isokinetic (mean 24%) strength was observed and maintained for some time. This
      demonstrates remaining adaptability in muscles already compensated from long
      standing polio.

PMID- 1985617
TI  - Arm ergometry exercise testing in patients with dysvascular amputations.
AB  - The purpose of this study was to test the agreement between the heart rate (HR)
      response and rating of perceived exertion (RPE) on an arm ergometry graded
      exercise test (GXT) in deconditioned persons with acute dysvascular amputations
      before and after an inpatient rehabilitation program. Twenty-six men were studied
      at admission, and 11 were retested after completion of the program. After
      obtaining resting measurements of HR and systolic and diastolic blood pressures,
      each patient performed the GXT using an arm ergometer. Patients maintained a
      cranking rate of 50rpm, which was monitored electronically. The workloads started
      with a warm-up period of 0 watts (stage 1) and increased by increments of 5
      watts. Each stage lasted three minutes-2.5 minutes of exercise and 30 seconds of
      rest. The RPE was taken five seconds before the end of each exercise stage.
      During the rest period, HR and blood pressures were recorded. Scatter plots and
      linear regression analyses revealed no statistically significant relationship,
      either at early stages of GXT or at peak work, between HR and RPE. The results
      suggest that RPE cannot be used reliably as a surrogate for direct pulse
      measurement in exercise training of persons with acute dysvascular amputations.

PMID- 1985618
TI  - Corticosteroid injections in adhesive capsulitis: investigation of their value
      and site.
AB  - Forty-eight patients with frozen shoulder for less than six months were assigned
      at random to receive three shoulder injections into the subacromial bursa or
      glenohumeral joint at weekly intervals. The treatment groups were (1) intra
      articular methylprednisolone and lidocaine, (2) intrabursal methylprednisolone
      and lidocaine, (3) intra-articular lidocaine, (4) intrabursal lidocaine. The same
      physical therapy program was carried out for all patients. Assessments of pain
      and range of motion were performed by a physical therapist who was uninformed
      about the nature of the injection therapy. There was no significant difference in
      outcome between intrabursal injection and intra-articular injection. Injection of
      steroid with lidocaine had no advantage over lidocaine alone in restoring
      shoulder motion, but partial, transient pain relief occurred in two thirds of the
      steroid-treated patients.

PMID- 1985620
TI  - Normal values for the soleus H-reflex in newborn infants 31-45 weeks post
      conceptional age.
AB  - Normal values for the soleus H-reflex were established in 83 preterm and term
      infants 31 to 45 weeks postconceptional age. Infants at conceptional ages 31 to
      34 weeks (n = 30) had a mean H-latency (msec) of 19.2 +/- 2.16; infants 35 to 39
      weeks (n = 26), 16.67 +/- 1.48; and infants 40 to 45 weeks (n = 27), 15.94 +/-
      1.45. Simple linear regression shows a significant relationship between
      conceptional age and H-latency (Pearson correlation = .68, R2 = 0.47, f = 71.31,
      p = .0001). Adjusting H-latency values for leg length, the regression of H-soleus
      latency/leg length (msec/cm) against conceptional age provides an even stronger
      relationship (r = 0.81, R2 = 0.66, f = 154.5, p = .0001). These results reflect
      the degree of myelination in infants of increasing conceptional ages. They can
      indicate the gestational age of the infants and afford comparative data in the
      event of peripheral nerve pathology.

PMID- 1985619
TI  - Spontaneous electromyographic potentials in chronic spinal cord injured patients:
      relation to spasticity and length of nerve.
AB  - Nine patients with complete cervical spinal cord injury (SCI) had their vastus
      medialis, tibialis anterior, and gastrocnemius muscles evaluated with an
      electromyographic (EMG) examination in the acute (four to eight weeks) and
      chronic (more than one year) phases. The hypothesis that spontaneous EMG activity
      changes with time was assessed. During the chronic phase evaluation, a conduction
      study was performed to rule out peripheral nerve damage, and the amount of reflex
      activity was assessed on a scale of 0 to 5 (0 = areflexia; 5 = greater than 5
      beats of clonus) to estimate the amount of spasticity. Subjects demonstrated
      normal conduction through the sensory (sural nerve) and/or motor segments of the
      peroneal and tibial nerves. In the acute phase, each muscle had spontaneous
      activity with no significant variation between different muscles of the same
      patient. In the chronic phase, there was a positive correlation between the
      degree of spontaneous activity in a muscle and the length of its axon (p less
      than .01) and a negative correlation between the amount of spontaneous activity
      and the degree of reflex activity (p less than .01). Specifically, the lower
      motor neuron in the chronic phase of an SCI seems to behave much like an
      axonopathy where the degree of spontaneous EMG activity is dependent on the
      length of the axon, with the additional concept that spontaneous activity is
      inhibited by spasticity.

PMID- 1985621
TI  - Multimodality evoked potential testing in acute mild closed head injury.
AB  - Multimodality evoked potential (MEP) testing, including brainstem auditory,
      visual, and somatosensory evoked potentials, have been reported to be useful in
      predicting outcome in severe closed head injury. Brainstem auditory evoked
      potentials have been demonstrated to be abnormal in 10% to 40% of acute mild head
      injury. A prospective study of 18 patients with mild closed head injury was
      undertaken to determine the usefulness of MEP screening within two weeks of the
      acute event. Long latency event-related potentials (P300s), in response to
      auditory stimuli with an oddball paradigm, were included in the screening. The
      subjects had several symptoms consistent with the postconcussive syndrome at the
      time of the evoked potential testing. Only one patient had an abnormal evoked
      potential response (greater than three standard deviations from the mean) from
      all the testing done. The standard methods of MEP testing were insensitive to
      quantifying the possible physiologic changes that are associated with memory
      deficits, lethargy, and emotional irritability after mild closed head injury.

PMID- 1985622
TI  - A tongue force measurement system for the assessment of oral-phase swallowing
      disorders.
AB  - A computer-aided measuring system using a highly sensitive beam transducer has
      been developed to provide a quantitative, reliable measure of tongue strength.
      This tool has application in both the diagnosis and treatment of dysphagic
      patients with oral-stage dysfunction. The device is customized to comfortably
      adapt to each individual. Audiovisual feedback is used to enhance subject
      interest and motivation. The device has proven reliable in measurements of upward
      and side tongue thrust in six able-bodied subjects measured during five separate
      sessions. It has also been used with two dysphagic patients.

PMID- 1985623
TI  - The ventilator-dependent child: issues in diagnosis and management.
AB  - Infants, children, and adolescents with chronic respiratory failure are surviving
      in increasing numbers and, thereby, producing a significant population of
      ventilator-dependent pediatric patients. Chronic respiratory failure can occur as
      a complication of a wide variety of disease states; in pathophysiologic terms, it
      generally results from either decreased central nervous system output or
      inadequate force generated by the respiratory pump. Its laboratory hallmark is
      hypercapnia with or without hypoxemia. Stabilization of the patient with
      mechanical ventilatory support may permit long-term survival. Management of the
      ventilator-dependent pediatric patient is a complex task that must begin with an
      accurate prognostication of each patient's survival and quality of life. Once a
      decision is made concerning the practicality and appropriateness of long-term
      ventilatory support, informed choices must be made with respect to need for an
      artificial airway, mode of ventilation, and location of care. Many younger
      patients, especially those with intrinsic lung disease (like bronchopulmonary
      dysplasia), may require a hospital setting for long-term care, whereas others
      with neuromuscular or central disorders may benefit from being discharged to
      home. The patient's family must be thoroughly educated in the child's care, and
      they must be involved in decision-making. A multidisciplinary team of physicians,
      therapists, nurses, and other professionals is required to deliver optimal care.
      Outcome is good for most patients who are carefully selected.

PMID- 1985624
TI  - Orthostatic hypotension after spinal cord injury: treatment with fludrocortisone
      and ergotamine.
AB  - We report a case of a 28-year-old woman with C5 quadriplegia, unresponsive to
      conservative treatment for orthostatic hypotension. Ergotamine, daily combined
      with fludrocortisone, successfully prevented symptomatic hypotension. In this
      report, neural, renal, and hormonal blood pressure regulatory mechanisms are
      described. Experiences obtained from this case and the existing literature
      suggest that (1) in persons with quadriplegia, plasma catecholamine levels show
      little increase with sitting, indicating an inability to activate baroreceptor
      and chemoreceptor reflexes, (2) elevated plasma aldosterone and renin levels
      indicate a renal compensatory response to decreased renal perfusion secondary to
      low plasma volume and/or chronic hypotension, and (3) the net effect of
      ergotamine and fludrocortisone is probably a combination of plasma volume
      expansion and direct peripheral vasoconstriction.

PMID- 1985625
TI  - Silent myocardial ischemia during rehabilitation for cerebrovascular disease.
AB  - In asymptomatic patients the importance of silent ischemic ST-T wave changes on
      Holter monitoring is known to be a significant predictive variable for one-year
      mortality of postmyocardial infarction patients. This case report represents the
      uses of ambulatory ECG to detect ischemic ST changes in patients who have had
      recent strokes. The cases reported here of silent myocardiac ischemia in stroke
      patients reflect previous reports in which 70% of the ischemic episodes in
      patients with symptomatic coronary artery disease are not associated with angina
      and in which approximately 10% to 15% of acute myocardial infarctions are silent.
      We now believe that the incidence of "silent" ischemia may be precipitated in
      poststroke patients during their rehabilitation program. This belief is supported
      by two main factors. First, a high level of personally relevant mental stress
      exists which activates the sympathoadrenal system, which may lead to myocardial
      ischemia. Second, some stroke patients become aphasic and are unable to
      communicate adequately even if they experience angina symptoms. We have found
      that poststroke, most patients could not undergo exercise treadmill testing
      secondary to a variety of factors: inability to coordinate limbs, poor endurance,
      inability to follow directions, and/or lack of attention. We now propose that 24
      hour monitoring for ST-T wave changes poststroke should be considered as part of
      a vigorous investigation for myocardial ischemia during the rehabilitation of
      these patients because they have an increased risk of cardiac morbidity.

PMID- 1985626
TI  - Neuromuscular function in polio survivors at one-year follow-up.
AB  - Many polio survivors complain of progressive loss of strength, work capacity,
      endurance, and ability to recover from fatiguing activity. These variables were
      measured initially and one year later in the quadriceps muscles of 28 symptomatic
      and 16 asymptomatic persons who had polio and 38 control individuals. Peak knee
      extension torque was measured isokinetically and isometrically. Endurance, or the
      amount of time the subject could maintain isometric torque at 40% of maximal
      torque, was measured. Work capacity was determined as the product of isometric
      torque and endurance time. Recovery of strength was measured at regular intervals
      for ten minutes after the endurance test. Statistical analysis was done by
      repeated measures ANOVA. Although the initial measures showed significant
      deficits in mean peak torque, work capacity, and recovery of strength in
      symptomatic postpolio subjects, no significant changes were found one year later
      in any of the variables. We conclude that symptomatic postpolio subjects do not
      lose significant neuromuscular function in one year.

PMID- 1985627
TI  - Oxygen-derived free radicals.

PMID- 1985628
TI  - Combined hepatic and vena caval resection with autogenous caval graft
      replacement.
AB  - Right-sided and caudate hepatic lobectomy with resection of the retrohepatic vena
      cava were performed in a 34-year-old woman with recurrent adrenal carcinoma. The
      vena cava was replaced with a graft constructed from autogenous superficial
      femoral vein. Included herein is a review of the literature detailing the three
      previously reported cases of combined hepatic and caval resection; to our
      knowledge, there are no prior reports of the use of an autogenous vein graft in
      this setting. With surgical and anesthetic techniques, including total vascular
      exclusion of the liver and venovenous bypass, methods that were developed in
      large part through experience in liver transplantation, this type of surgery can
      be performed with a high rate of success.

PMID- 1985629
TI  - Lower extremity arterial disease in systemic lupus erythematosus.
AB  - Lupus vasculitis primarily affects microvascular circulation, and large-vessel
      thrombosis is a rare complication of this disease. Large-vessel occlusive disease
      in systemic lupus erythematosus is most likely related to hypercoagulability in
      addition to immune complex-mediated endothelial damage. We describe the 11th and
      12th patients reported to have systemic lupus erythematosus and macrovascular
      occlusive disease of the lower extremities. Our experience and a review of the
      literature suggest that, while aortoiliac disease is amenable to bypass or
      endarterectomy, infrainguinal disease is rarely correctable surgically, and
      amputation becomes necessary in most of these patients.

PMID- 1985630
TI  - EEG monitoring in carotid endarterectomy.

PMID- 1985631
TI  - Mandatory exploration for penetrating abdominal wounds.

PMID- 1985632
TI  - Retrospect and prospect. Ruminations after the first decade of the Surgical
      Infection Society.

PMID- 1985633
TI  - Organ interactions in sepsis. Host defense and the hepatic-pulmonary macrophage
      axis.
AB  - Endotoxin (lipopolysaccharide [LPS]) and tumor necrosis factor (TNF-alpha) have
      been implicated in the pathogenesis of sepsis-induced adult respiratory distress
      syndrome. To evaluate the possible interaction of the hepatic-pulmonary
      macrophage axis in the adult respiratory distress syndrome, we compared the
      kinetics of immunosuppressive prostaglandin E2, TNF-alpha, and interleukin 6
      production in LPS-stimulated Kupffer cells and alveolar macrophages (AMs).
      Interleukin 6 production by Kupffer cells was significantly higher than for equal
      numbers of AMs. Kupffer cell TNF-alpha levels peaked early before decreasing as
      regulatory prostaglandin E2 levels rose. In contrast, AM TNF-alpha levels rose
      sharply and remained significantly higher than for Kupffer cells throughout
      culture coincident with negligible prostaglandin E2 production. Kupffer cell
      sequestration of LPS may normally invoke a coordinated cytokine response able to
      locally induce acute-phase hepatocytes. In hepatic failure, however, LPS
      spillover to the lung may promote adult respiratory distress syndrome by inducing
      unregulated AM TNF-alpha production within the pulmonary microenvironment.

PMID- 1985634
TI  - Fungal burn wound infection. A 10-year experience.
AB  - To evaluate our experience with fungal burn wound infection, we performed a 10
      year review for comparison with our experience with bacterial burn wound
      infection. During the study period, a marked decline occurred in bacterial wound
      infection but not in fungal wound infection. Patients with either bacterial or
      fungal burn wound infection had massive injury, with burn size averaging greater
      than 50% of the total body surface area. Factors that appear to have markedly
      reduced bacterial burn wound infection, including patient isolation, topical
      chemotherapeutic agents, and burn wound excision, do not appear to have had a
      similar effect on fungal wound infection. The mechanism of spread and
      colonization of fungi, and the lack of effective topical chemotherapeutic
      antifungal agents, may explain in part our findings.

PMID- 1985636
TI  - Indications for surgical debridement in 125 human bites to the hand.
AB  - Indications for operative intervention following human bites to the hand were
      determined based on physical examination and time elapsed since injury. One
      hundred twenty-four patients admitted to Charity Hospital of New Orleans, La,
      were stratified according to time elapsed from injury to treatment (early, less
      than 24 hours; delayed, 1 to 7 days; and late, greater than 7 days). Patients in
      the early group were mainly treated with conservative wound care, consisting of
      local wound exploration and irrigation in the emergency department, while those
      in the late group underwent surgical debridement. Patients in the delayed group
      either received conservative wound care or underwent debridement in the operating
      room. The early and late groups recovered excellent hand function while results
      within the delayed group were variable with improved results depending on rapid
      surgical debridement or drainage.

PMID- 1985635
TI  - Alterations in host defense associated with anesthesia and blood transfusions.
      II. Effect on response to endotoxin.
AB  - The effect of blood transfusions and anesthesia on host response to endotoxin was
      evaluated in multiple Lewis rat models. The rats were randomized to receive
      A'Sogaloff Cancer Institute rat blood, pentobarbital sodium, or lactated Ringer's
      solution and, at either 2 or 7 days following administration of these agents,
      were challenged with intravenous endotoxin. Neither blood transfusions nor
      anesthesia altered mortality when administered 2 days before endotoxin challenge.
      However, blood transfusions administered 7 days before endotoxin challenge were
      found to prolong survival, to prevent endotoxin-induced alterations in T
      lymphocyte subsets, and to decrease plasma tumor necrosis factor levels. In
      conclusion, blood transfusions appear to depress immune function in a beneficial
      manner in endotoxin shock.

PMID- 1985637
TI  - Tumor necrosis factor and endotoxin can cause neutrophil activation through
      separate pathways.
AB  - We investigated the possibility that tumor necrosis factor (TNF) mediates
      neutrophil activation by endotoxin. The number of C3b receptors on the neutrophil
      cell-surface was used as the indicator of activation, as assessed by indirect
      immunofluorescence. Incubation of buffy-coat neutrophils with TNF-alpha for 30
      minutes at 37 degrees C caused neutrophil activation, increasing C3b receptor
      dependent fluorescence from 340 with buffer alone to 580 with TNF (250 pg/mL).
      Increasing amounts of anti-TNF IgG progressively inhibited neutrophil activation
      by TNF (250 pg/mL). Addition of the active dose range of anti-TNF to neutrophils
      incubating in endotoxin (10 ng/mL) did not affect the degree of endotoxin
      mediated neutrophil activation. Mixtures of neutrophils with the 50% suppressive
      dose of anti-TNF and varying endotoxin concentrations showed the same degree of
      neutrophil activation as mixtures without the antibody. Thus, an antibody that
      can inhibit TNF-mediated neutrophil activation does not inhibit endotoxin
      mediated neutrophil activation. We conclude that endotoxin and TNF can activate
      neutrophils through separate pathways.

PMID- 1985638
TI  - Effect of aerosolized fibrin solution on intraperitoneal contamination.
AB  - The potential deleterious effects of aerosolized fibrin on contaminated
      procedures were investigated in a rat model of peritonitis. One hundred forty
      rats were divided into two groups. In the control group, gelatin capsules
      containing feces (10(7) bacteria per milliliter) and barium sulfate at various
      dilutions were placed into the abdomen; in the second experimental group, a
      solution of cryoprecipitate, thrombin, and calcium was sprayed diffusely into the
      peritoneal cavity after similar fecal contamination. Fecal inocula with low
      bacterial concentrations (0.01, 0.1, and 0.15 mL) caused few deaths from
      peritonitis or abscess formation in either group. Heavy peritoneal contamination
      (0.25, 0.3, and 0.5 mL) caused early deaths from peritonitis in both groups, with
      80% of the deaths due to sepsis in the first 48 hours. However, in the moderately
      contaminated rats (0.2 mL of fecal inoculate), fibrin aerosol reduced the 10-day
      mortality from 80% to 10%. In all survivors in the fibrin-treated group,
      intraperitoneal abscesses developed. With intraperitoneal bacterial
      concentrations of 2 x 10(6) organisms, early acute mortality from fibrinopurulent
      peritonitis is decreased at the expense of late, localized, nonlethal abscess
      formation. Aerosolized fibrin solution must be used with caution in contaminated
      surgery.

PMID- 1985639
TI  - The epidemiologic features of nosocomial infections in patients with trauma.
AB  - Sepsis is a major cause of morbidity and mortality in patients with trauma. To
      elucidate factors that might lead to infection, we studied the epidemiologic
      characteristics of nosocomial infections in our patient population with trauma.
      During a 3.5-year period, 2496 patients were entered into our hospital trauma
      registry and cross-matched with hospital infection control surveillance
      information. Two hundred twenty-nine patients with trauma and nosocomial
      infections were identified (9.2%), a figure that was nearly twice the nosocomial
      infection rate for the general hospital population. The majority of those
      infected were either orthopedic (51%), general surgical (25%), or neurosurgical
      (13%) patients. The most common sites of first infection were urinary tract (61%)
      or respiratory system (14%). Patients developing nosocomial infections were
      significantly older and had a higher Injury Severity Score than those who did
      not. Injury site was related to risk of infection with injuries of the spine,
      chest, and extremity showing the most significant relationship. The length of
      stay as well as hospital charges were significantly related to the occurrence of
      infectious complications. By determining the patient with trauma at risk for
      infection, treatment strategies can be designed to minimize septic complications.

PMID- 1985640
TI  - Intussusception and the diagnostic value of testing stool for occult blood.
AB  - A retrospective review was performed to determine the diagnostic value of testing
      for occult blood in stool of children suspect for intussusception. Ninety-six
      children had barium enema studies for suspected intussusception. Of the 57
      children who had barium enema confirmed intussusception, 29 did not have history
      or physical findings of gross blood per rectum. Stool was tested for occult blood
      in 16 of these 29 patients, and 12 (75%) were positive. In comparison, three
      (20%) of the children who did not have intussusception had stool positive for
      occult blood. Stool with occult blood was significantly associated with
      intussusception (P less than .002). The only other clinical factor significantly
      associated with intussusception was abdominal mass (P less than .02). Vomiting,
      episodic irritability, poor feeding, abdominal pain and lethargy were not
      significantly different in the two groups. In conclusion, the authors suggest
      stool testing for occult blood when evaluating children who present with
      nonspecific signs and symptoms supportive of intussusception.

PMID- 1985641
TI  - Poisonings in laboratory personnel and health care professionals.
AB  - A case report of an unresponsive chemist presenting to the emergency department
      is presented; in retrospect, the patient was discovered to have intentionally
      ingested cyanide. A review of literature regarding ingestions in laboratory and
      health care personnel reveals five common points encountered in these personnel:
      barbiturates, carbon monoxide, cyanide, azides, and methemoglobin-inducing
      chemicals. Key diagnostic findings, in the absence of history of exposure, are
      discussed for these five agents.

PMID- 1985642
TI  - Oral indomethacin for acute renal colic.
AB  - A number of studies have suggested that nonsteroidal antiinflammatory agents can
      relieve renal colic by a mechanism of action different from that of narcotics,
      offering the potential advantage of avoiding narcotic side-effects such as
      alteration of mental status. The authors prospectively administered oral
      indomethacin, 50 mg, to 25 nonvomiting patients with acute renal colic due to a
      documented stone. Eleven patients group (I) received the drug in an unblinded,
      nonrandomized fashion after failure of oral or parenteral narcotics to provide
      satisfactory pain relief, either at home or in the emergency department. In 14
      additional patients group (II) indomethacin was given as the only initial
      treatment. Pain intensity before and after treatment was reported using a 1-to-10
      scale. In group I, pain decreased from 5.8 +/- 2.7 to 3.6 +/- 3.8 (P less than
      .02). Six of the 11 patients reported a decrease in pain intensity of 50% or
      more, which occurred within 25 +/- 11 minutes, and in 5 of these 6, pain
      decreased to a 0 or 1 level. In group II, pain decreased from 7.6 +/- 1.5 to 4.6
      +/- 4.0 (P less than .008). Eight of the 14 patients reported a decrease in pain
      intensity of 50% or more, which occurred within 40 +/- 14 minutes, and in 5 of
      these 8 pain decreased to a 0 or 1 level. Among all 25 patients who received
      indomethacin, pain relief was not significantly associated with the duration of
      pain before treatment or with patient age or sex. There was a trend for
      pretreatment pain intensity to be higher among nonresponders (P = .07).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1985643
TI  - An evaluation of cannulae and oxygen sources for pediatric jet ventilation.
AB  - The authors evaluated the cannulae and oxygen sources available for pediatric
      translaryngeal ventilation. Peak flow rates were measured and maximum tidal
      volumes (MTV) calculated for each combination of cannula and oxygen source.
      Standard 22, 20, 18, and 16 gauge intravenous catheters and a 14 gauge cannula
      designed for pediatric jet ventilation were tested. The oxygen sources evaluated
      included an adult bag-valve device; a continuous flow source regulated between 6
      to 15 L/min; and a high pressure jet source regulated between 5 to 50 psi. Mean
      calculated MTV delivered to the cannula tip (22 g to 14 g) were: 26 to 235 mL
      with the bag-valve source; 91 to 236 mL with the continuous flow sources; and 58
      to 1034 mL with the jet sources. Assuming that in normal subjects approximately
      70% of the flow from the tip of a translaryngeal cannula reaches the distal
      respiratory tree, the authors conclude that bag-valve and continuous flow low
      pressure sources are unlikely to deliver sufficient tidal volumes to sustain
      normal ventilation in apneic children when coupled with standard cannulae. Jet
      oxygen sources with standard cannulae provide a wide range of tidal volumes
      sufficient to sustain normal ventilation in apneic pediatric patients.

PMID- 1985644
TI  - Absorption of iron after experimental overdose of chewable vitamins.
AB  - Even though ingestion of chewable iron preparations is much more common,
      treatment recommendations for iron overdose are usually based on experience with
      nonchewable preparations. To determine the optimal time to measure serum iron
      concentrations, five volunteers were given chewable iron in 5 mg/kg and 10 mg/kg
      doses and their serum iron concentrations monitored. Peak levels occurred at 4.2
      and 4.5 hours, respectively, after ingestion, and levels drawn at 3 hours were
      within 90% of the peak. Nausea and headache were experienced by all volunteers,
      and serum iron exceeded baseline total iron binding capacity in two subjects at
      the 10 mg/kg dose. In minor iron overdose resulting from the ingestion of
      chewable vitamins, serum iron concentrations measured between 3 and 7 hours (95%
      confidence level of peak concentrations) may be adequate in assessing the peak
      serum iron concentration.

PMID- 1985645
TI  - Adult respiratory distress syndrome from organophosphate poisoning.
AB  - A 46-year-old man after an accidental exposure to organophosphates developed
      florid adult respiratory distress syndrome (ARDS). A markedly suppressed level of
      pseudocholinesterase and red blood cell cholinesterase with profuse salivation
      and sweating confirmed the diagnosis of organophosphate poisoning. Within 48
      hours, patient developed respiratory distress needing intubation. Despite maximum
      ventilatory support and positive end-expiratory pressure, hypoxia persisted, Swan
      Ganz (Baxter Healthcare Inc, Irvine, CA) pressures showed low pulmonary capillary
      wedge pressure and patient died on the third hospital day. An autopsy confirmed
      the picture of ARDS. Other potential causes of ARDS were excluded. Although rare,
      organophosphate poisoning should be added to the list of toxins causing ARDS.

PMID- 1985646
TI  - Open depressed skull fracture missed on computed tomography: a case report.
AB  - A case of an open depressed skull fracture that was missed on standard computed
      tomographic (CT) scan is presented. The fracture was seen on a CT generated
      lateral scout film, and after repositioning the gantry, further CT images clearly
      showed the fracture and underlying brain injury. The authors recommend that all
      patients with head trauma undergoing head CT have either a CT generated lateral
      scout film or a lateral skull radiograph to assess the vertex of the skull, an
      area poorly visualized on standard axial images.

PMID- 1985647
TI  - Mediastinitis following nasal intubation in the emergency department.
AB  - A patient who developed a retropharyngeal abscess and fatal mediastinitis
      following emergent nasal intubation is described. Despite aggressive surgical
      therapy the patient died of mediastinitis. Although mediastinitis as a
      complication of oral intubation has been described, mediastinitis following nasal
      intubation has not previously been reported.

PMID- 1985648
TI  - Seatbelt effectiveness and cost of noncompliance among drivers admitted to a
      trauma center.
AB  - Enactment of seatbelt legislation in Maryland presented the opportunity to
      compare seatbelt compliance among seriously injured drivers admitted to a Level I
      trauma center and to establish levels of severity, length of stay, and hospital
      cost differences among the study population. Fifty-five randomly selected drivers
      were examined from a total surgical population of 689. Seatbelt compliance rate
      was 41.8%, reflecting the rate in the community. Seatbelts reduced the total
      number of injuries by 34%, major injuries by 57%, and minor injuries by 20%. No
      deaths occurred among the belted group. The unbelted group had a mean Injury
      Severity Score two times as great as the belted group and were hospitalized 1.6
      times longer at double the cost. Major injuries to the face, chest, and pelvic
      regions were prevented by the seatbelt. Among the belted group, severe injuries
      did occur to the head, neck, and abdominal regions. It is recommended that both
      air bags and automatic restraining devices be required for all drivers if the
      trauma occurring daily on highways is to be eliminated and acute hospital cost
      minimized.

PMID- 1985649
TI  - Testicular dislocation following minor scrotal trauma.
AB  - Traumatic dislocation of the testicle is a rare injury generally resulting from
      severe scrotal trauma and displacement of the testicle into the subcutaneous
      tissue surrounding the external inguinal ring. The authors report here the
      extremely unusual case of an abdominal dislocation of the testicle in a young
      patient with an indirect inguinal hernia. In addition this case is particularly
      atypical in that the injury resulted from a trivial blow to the scrotum. A new
      mechanism involving preloading of the cremaster muscle as the source of the
      dislocation is postulated.

PMID- 1985650
TI  - Carbidopa-levodopa overdose.
AB  - A 57-year-old woman ingested 15 to 17 tablets of carbidopa-levodopa 10/100
      tablets (carbidopa 150 mg and levodopa 1,500 mg) along with ibuprofen,
      carisoprodol, hydrocodone, and acetaminophen. The patient developed choreiform
      movements that persisted despite obtundation and attempts to extinguish them with
      naloxone, morphine, and diazepam. When the patient developed a rising level of
      creatine phosphokinase and myoglobinuria, she was treated with ventilatory
      support and pancuronium. She required paralysis for 60 hours, when her chorea
      resolved.

PMID- 1985651
TI  - Vertebrobasilar occlusion following minor trauma in an 8-year-old boy.
AB  - An 8-year-old boy developed seizures and coma 2 days after a trivial bicycle
      accident. Computed tomography failed to show pathology. Magnetic resonance
      imaging of the head showed infarction of the pons and right cerebellum.
      Angiography showed occlusion of the right vertebral and basilar arteries. Minor
      traumatic injuries to the cervical spine may result in vertebrobasilar occlusion.
      The neurologic manifestations of this disorder and emergency department diagnosis
      and management are discussed.

PMID- 1985652
TI  - Cat-scratch disease: an unusual cause of combative behavior.
AB  - Acute encephalitis is an unusual manifestation of cat-scratch disease. The
      authors present the case of a 27-year-old man who exhibited the acute onset of
      encephalitis manifested by violent behavior and confusion. The diagnosis of drug
      abuse was presumed initially, but a careful examination revealed the true cause
      to be cat-scratch disease. Emergency physicians are frequently faced with the
      challenging task of evaluating confused and combative patients. This case
      demonstrates the importance of a complete physical examination and a thorough
      laboratory evaluation.

PMID- 1985653
TI  - Sudden cervical pain: spontaneous cervical epidural hematoma.
AB  - Three cases of cervical epidural hematoma are reported. Acute neck pain usually
      associated with a mild effort, closely followed by radicular pain and a
      neurologic deficit below the lesion is the typical presentation of this extremely
      rare and difficult diagnosis. As prognosis depends on preoperative neurologic
      state, the authors emphasize the importance of prompt identification of this
      lesion. The diagnosis is confirmed by computed tomography, and emergency
      neurosurgical laminectomy is mandatory.

PMID- 1985654
TI  - The febrile alcoholic in the emergency department.
AB  - The authors retrospectively reviewed the charts of 31 alcoholic patients admitted
      with fever without a defined source. In our population 58% of patients were
      subsequently found to have an infectious cause for their fever. Pneumonia was the
      most common infection, but occult urinary tract infections were seen surprisingly
      often. Noninfectious but serious disorders, such as delirium tremens, prolonged
      postictal state, and subarachnoid hemorrhage, were also common. Infectious and
      noninfectious causes commonly coexisted. The most common noninfectious cause was
      alcohol withdrawal, with or without seizures. The authors believe that indigent,
      malnourished, chronic alcoholics with fever for which a source cannot be readily
      identified, should usually be admitted to the hospital for observation and to
      await culture results.

PMID- 1985655
TI  - The Three Rivers Regatta accident: an EMS perspective.
AB  - The Three Rivers Regatta accident occurred on August 7, 1988 when a Formula I
      racing craft collided with shore, injuring 24 spectators. The authors
      retrospectively examined the prehospital-based response for this multiple
      casualty incident that used emergency medical service (EMS) physicians and 32
      paramedics stationed at water and land-based posts to triage and evacuate 24
      patients in 32 minutes. Patients were transported to 5 hospitals including 4
      Level I trauma centers; this was accomplished in 53 minutes. The EMS response was
      unique in a number of respects. This was a prehospital-based rescue with the
      entire triage and stabilization phase accomplished by River Rescue units that
      transported paramedic divers, EMS physicians, and trauma supplies for 30
      patients. Also of significance was the inordinate proportion of pediatric
      patients that accounted for 50% (12/24) of the cases. Successful medical care was
      the result of planning based on "Daily Routine Doctrine" or escalation of
      existing treatment protocol; adequate supplies, personnel and transport adapted
      to local geography and patient population; communications, including all services
      -EMS, police, and fire; and prehospital physician input to ensure correct triage
      order and patient disposition.

PMID- 1985656
TI  - Removal of obstructed Foley catheter from the urethra.
AB  - This case illustrates an approach to resolve a frustrating problem associated
      with Foley catheter balloon obstructions. By identifying its position in the
      urethra, the balloon can be deflated with minimal effort and limited urethra
      injury, using the suggested technique of transperineal needle insertion.

PMID- 1985657
TI  - The role of emergency department in thrombolytic therapy in acute myocardial
      infarction.

PMID- 1985658
TI  - Bystander cardiopulmonary resuscitation (CPR): the next decade.

PMID- 1985659
TI  - Primary board status: only the end of the beginning.

PMID- 1985660
TI  - Automated external defibrillators and ACLS: a new initiative from the American
      Heart Association.

PMID- 1985661
TI  - A guide for replacing the leaky ETT.

PMID- 1985662
TI  - Heparin lock use.

PMID- 1985663
TI  - An unusual diagnosis for acute right-sided groin pain in a 39-year-old woman.

PMID- 1985664
TI  - Immobilization and extrication of trauma patients by untrained personnel.

PMID- 1985665
TI  - Spiral tibial fractures revisited.

PMID- 1985666
TI  - Intraosseous digoxin immune FAB.

PMID- 1985667
TI  - Forty years of litigation involving medical students and their education: I.
      General educational issues.
AB  - An analysis of reported state and federal adjudication from 1950 through 1989 was
      undertaken to identify trends in litigation involving medical students and
      undergraduate medical education. Of the 110 decisions cited, 51 (46%) involved
      disputes over general educational issues. A majority of the decisions affecting
      general education involved admissions and dismissal processes. Recently courts
      have begun scrutinizing readmission, course repetition, and cheating. Medical
      schools have accommodated to judicial scrutiny of general educational issues and
      have prevailed more often than claimants in litigation during this period, but
      litigation has not decreased as precedent and procedure have become clearer.
      Instead, litigation has continued unabated in alternative areas and at different
      levels of the educational process.

PMID- 1985668
TI  - Assessing competency to address ethical issues in medicine.

PMID- 1985669
TI  - Medical knowledge bases.

PMID- 1985670
TI  - The Physician Payment Review Commission.

PMID- 1985671
TI  - Preventing faculty wars.

PMID- 1985672
TI  - In-training examinations.

PMID- 1985674
TI  - Learning to care for the dying: a survey of medical schools and a model course.
AB  - Education on death and dying is relatively new in the United States; a recent
      survey indicated that there is little consensus on teaching methods and content
      of courses. This paper reports the authors' 1989 survey of 111 U.S. medical
      schools, and describes a death and dying seminar offered at the Yale School of
      Medicine using patients as teachers. Regarding the survey, the authors mailed
      questionnaires to 124 schools; 111 responded. Twelve of the schools (11%)
      provided no formal teaching in death and dying. Of the 99 schools that did, 30
      provided one or two lectures in the first two years. Fifty-one schools taught
      death and dying as a module of a larger required course, and 18 schools offered
      an elective. Lecture was the predominant teaching method, and patient
      participation was usually restricted to a class presentation. Regarding the Yale
      seminar, each student meets individually with a patient during the semester and
      in small groups with the instructor to discuss the interviews, personal
      reactions, and professional issues in the care of his or her patient-teacher.
      This seminar enables students to learn the personal effects of serious illness,
      coping techniques used in daily living, characteristics of the caring physician,
      and skills needed to provide compassionate care.

PMID- 1985673
TI  - Comparing students' feedback about clinical instruction with their performances.
AB  - Validation of students' feedback as a measure of teaching effectiveness has been
      problematic for courses teaching clinical skills. This is true in part because
      establishing a valid and reliable method of assessing students' mastery of
      clinical skills has been a stumbling block. Reported here is the correlation of
      students' performances on an objective structured clinical examination (OSCE)
      with previously and independently collected feedback from students. In 1987-88,
      190 second-year medical students at the University of Minnesota Medical School-
      Minneapolis spent one fourth of a second-year clinical skills course on neurology
      randomly assigned to one of four teaching sites--hospitals A, B, C, and D.
      Following their rotations, 180 of the students completed usable feedback forms.
      The students were consistently and significantly more positive about the teaching
      at hospital A. At the end of the year, all 190 students were tested using an OSCE
      having 20 stations, four of which presented neurologic problems. The students who
      had the neurology course at hospital A performed better on all four neurology
      problems, and differences were statistically significant for two of the problems.
      Feedback in this case accurately reflected a more effective teaching program.

PMID- 1985675
TI  - How issues of professional liability are taught in U.S. medical schools.
AB  - This study investigated how medicolegal issues--specifically those concerning
      professional liability--are treated in U.S. medical school education. The author
      mailed a questionnaire in mid-1989 to all 127 U.S. medical schools that were
      accredited at that time and to the five medical school campuses of the University
      of Illinois; 120 (90%) responded. Of these, 73 (61%) reported that they included
      topics about professional liability in their educational curricula. Twenty-three
      of the schools indicated that students' training had been "compromised or
      jeopardized" by the impact of physicians' concerns about medicolegal issues.
      Forty-seven of the schools had students who had been named in malpractice suits.
      The study shows that undergraduate medical education has been significantly
      affected by issues of professional liability. Relevant medicolegal content should
      be an integral part of medical school education.

PMID- 1985676
TI  - Why medical students choose primary care careers.
AB  - To determine what factors distinguish medical students who choose primary care
      careers, 381 graduating medical students at eight New England medical schools
      were surveyed by questionnaire prior to the 1988 National Resident Matching
      Program. Students were asked to indicate the degrees of influence that various
      factors had on their specialty choices, using a Likert-type scale ranging from
      "totally unimportant" to "decisive." Compared with their peers who chose high
      technology specialties, those who chose primary care were more likely to be
      motivated by the opportunities to provide direct patient care (p less than .001),
      care in an ambulatory setting (p less than .001), and continuity of care (p less
      than .001) and the opportunity to be involved in the psychosocial aspects of
      medical care (p less than .001). Those who chose high-technology specialties were
      more likely to be motivated by desires for a large income (p less than .001) and
      more prestige (p less than .005), and the opportunities for research (p less than
      .001), more regular hours (p less than .005), more leisure and family time (p
      less than .001), and a better call schedule as a resident (p less than .01).
      Neither student age, race, sex, marital status, and level of debt nor concern
      about the increasing regulation of medical practice, malpractice, health manpower
      reports, and the increasing numbers of elderly, chronically ill, and AIDS
      patients were found to be significant factors in the students' choice of primary
      care.

PMID- 1985677
TI  - Comparing physicians' specialty interests upon entering medical school with their
      eventual practice specialties.
AB  - The stability of specialty choices of 519 graduates of the University of
      Washington School of Medicine were studied by means of a mail survey in 1986. The
      graduates' actual practice specialties were compared with the one or more
      specialties each had indicated as possible career specialty choices when they
      entered medical school. Nearly 70% of the graduates' early choices remained
      stable, double the percentage found by other studies that based stability on an
      entering medical student's single choice of a career specialty. The findings
      suggest that students entering medical school have in mind a variety of
      acceptable specialties and later are likely to choose one of these as a career.

PMID- 1985678
TI  - Differences in residency performances and specialty choices between graduates of
      three- and four-year curricula.
AB  - This study identified differences in the specialty choices and residency program
      directors' performance ratings of residents graduated from two different
      curricula of the same medical school. One curriculum was three years long, and
      compressed two years of the basic sciences into one year of study. The other was
      a four-year program devoting two years each to the basic and clinical science,
      but with elements unifying the two areas. Using an 18-item form, the program
      directors rated the performance of 42-96% of the residents who had graduated in
      the classes of 1982, 1984, 1985, and 1986. (1982 was the only class of the three
      year curriculum that was studied.) Graduates of the three-year program showed
      less strength in background medical knowledge and in their experience of using
      research data; their greatest strengths seemed to be in the sorts of skills that
      normally would be acquired during the course of residency experiences. Graduates
      of the four-year curriculum seemed more able to integrate background medical
      knowledge and effective care of patients. Their weaknesses appeared to be in
      those skills that would be developed during the course of the residency
      experience. The only marked differences between the two groups in terms of
      residency specialty choice were in surgery and medicine.

PMID- 1985679
TI  - Investigating whether medical students' intolerance of ambiguity is associated
      with their specialty selections.
AB  - At one medical school in 1982, 175 entering medical students indicated their
      medical specialty preferences, completed Budner's Intolerance of Ambiguity scale,
      and supplied demographic information. Most (91%) completed medical school, and
      their specialty choices at graduation from the National Resident Matching Program
      were recorded. Initial specialty preference was a poor predictor of later
      specialty choice (R2 = .11). The students' intolerance of ambiguity was not
      significantly associated with either their initial medical specialty preferences
      or their specialty choices at graduations. This finding supports previous studies
      showing that specialty preferences changed dramatically during medical school,
      but does not reveal any support for a relationship between students' initial
      intolerance of ambiguity and their specialty selections.

PMID- 1985680
TI  - A two-year experience with premedical postbaccalaureate students admitted to
      medical school.
AB  - To determine how well premedical postbaccalaureate students performed in and
      adjusted to medical school, the author examined the records for all 123
      matriculants to the Brown University Program in Medicine in 1987-88 and 1988-89
      and sent each student a questionnaire. More than one-third of the first-year
      students admitted to Brown were from premedical postbaccalaureate programs (that
      is, they had taken the traditional premedical course requirements after
      graduating from college). The postbaccalaureate students were older than the rest
      of their classmates, on average, and were more likely to have been non-science
      majors in college. Academic performances over the first two years were comparable
      in the two groups, and there was no significant difference between the groups in
      their self-reports of adequacy of preparation or involvement in extracurricular
      activities. The author concludes that, faced with a smaller applicant pool,
      medical schools may wish to consider premedical postbaccalaureate students as a
      valuable resource.

PMID- 1985681
TI  - Characteristics of effective clinical teachers of ambulatory care medicine.
AB  - This study identified characteristics of clinical teachers in ambulatory care
      settings that influenced ratings of overall teaching effectiveness and examined
      the impacts of selected variables of the clinic environment on teaching
      effectiveness ratings. A survey instrument derived from prior research and
      observations of ambulatory care teaching was sent to 165 senior medical students
      and 60 medicine residents at the University of Washington School of Medicine in
      1988. A total of 122 (74%) of the seniors and 60 (71%) of the residents
      responded. Results indicate that the most important characteristics of the
      ambulatory care teachers were that they actively involved the learners, promoted
      learner autonomy, and demonstrated patient care skills. Environmental variables
      did not have a substantial influence on these ratings.

PMID- 1985682
TI  - An assessment of 15 years' experience in using videotape review in a family
      practice residency.
AB  - Videotechnology provides a new vehicle to augment experiential learning in
      medical education. This report is an assessment of 15 years' experience in the
      use of videotape review in a family practice residency program, and identifies a
      number of specific issues and principles that were found useful to faculty in the
      development of teaching strategies when using this technique. The strength and
      potential benefits of videotape review in medical education are discussed.

PMID- 1985683
TI  - Development and evaluation of a learning-strategies/peer-tutorial program for
      first-year medical students.

PMID- 1985684
TI  - Use of the matriculating student questionnaire with students from an eight-year
      combined baccalaureate-medical degree program.

PMID- 1985685
TI  - The cognitive structures students used to organize what they learned in a
      psychiatry clerkship.

PMID- 1985686
TI  - Increasing the number of competing awards at the National Heart, Lung, and Blood
      Institute: projections of a model.
AB  - In the mid 1980s, the National Heart, Lung, and Blood Institute (NHLBI) sought to
      extend the benefits of longer award terms to the research community by supporting
      requests for longer award terms that were scientifically justified. Although
      investigators welcomed the resultant increase in support stability, concerns were
      raised about the institute's ability to fund competing awards. A model was
      developed to assess alternative policies that might result in increased numbers
      of competing awards. Assuming that the NHLBI receives budget increases sufficient
      only to keep pace with inflation, the transitory effects of moving to the current
      policy of longer award terms should largely have passed by 1993. In the long
      term, the annual number of competing awards will exceed the average number funded
      between 1980 and 1983. To increase the annual number of competing awards over the
      long term would require either a reduction in the current percentage of five-year
      awards or an increase in the total number of active grants. A reduction in the
      current percentage of five-year awards would subject productive scientists to
      greater instability in their research support (that is, they would have to apply
      more frequently for grants) and would introduce greater variability in the number
      of competing awards available each year. A substantial increase in the total
      number of active NHLBI awards would be necessary to return the institute's
      competing awards to the levels of 1984 to 1988.

PMID- 1985687
TI  - Strategies for establishing a nursing research program.

PMID- 1985688
TI  - Current problems confronting community health services--part 2.

PMID- 1985689
TI  - Beyond hemoglobin polymerization: the red blood cell membrane and sickle disease
      pathophysiology.

PMID- 1985690
TI  - Hybridization protection assay: a rapid, sensitive, and specific method for
      detection of Philadelphia chromosome-positive leukemias.
AB  - The Philadelphia (Ph1) chromosome is present in greater than 90% of patients with
      chronic myelogenous leukemia (CML) and in 2% to 20% of those with acute
      leukemias, for which it is an important prognostic marker too. The chimeric BCR
      ABL mRNAs resulting from the translocation encode either a 210-Kd or a 190-Kd
      protein. The techniques used to detect Ph1 chromosome include karyotyping,
      Southern analysis to demonstrate bcr rearrangement, and polymerase chain reaction
      to amplify the BCR-ABL transcripts. However, the routine performance of these
      methods by clinical laboratories is cumbersome, time consuming, and exposes
      laboratory personnel to radioisotopes. We describe here the clinical application
      of a new method, the hybridization protection assay (HPA), which uses
      chemiluminescent acridinium-ester-labeled probes in conjunction with PCR for
      detection of the amplified BCR-ABL sequences. The method is sensitive, specific,
      and can reliably distinguish between the transcripts for P190BCR-ABL and P210BCR
      ABL. In contrast to the 2 days or longer required for conventional hybridization,
      HPA analysis can be completed in less than 30 minutes. We have successfully used
      this method to analyze 60 leukemia samples (34 from Ph1-negative acute leukemias;
      6 from Ph1-positive acute leukemias; and 20 from CML) with complete correlation
      (of BCR-ABL positivity or negativity) with the results of karyotype or Southern
      Blot analysis of genomic DNA for bcr rearrangement. Therefore, the HPA, in
      conjunction with PCR, appears to provide a rapid and reliable test for the
      diagnosis of Ph1-positivity.

PMID- 1985691
TI  - Reduction of graft failure by a monoclonal antibody (anti-LFA-1 CD11a) after HLA
      nonidentical bone marrow transplantation in children with immunodeficiencies,
      osteopetrosis, and Fanconi's anemia: a European Group for
      Immunodeficiency/European Group for Bone Marrow Transplantation report.
AB  - Forty-six infants and children suffering from either inherited immunodeficiency
      disorders (Wiskott-Aldrich syndrome, functional T-cell immunodeficiency with or
      without HLA class II expression deficiency), malignant osteopetrosis, or
      Fanconi's anemia received HLA-nonidentical bone marrow transplantation (BMT) from
      related donors. Bone marrow was T-cell depleted to reduce the risk of graft
      versus-host disease (GVHD). To prevent graft failure, a mouse monoclonal antibody
      specific for the CD11a-lymphocyte function-associated antigen 1 (LFA-1) molecule
      was infused into the patients. Eleven patients received five infusions of 0.1
      mg/kg every other day from day -3 to +5. Thirty-five patients received 0.2 mg/kg
      daily from day -3 to +6. The overall sustained engraftment rate was 72% instead
      of 26.1% in a historical control group of 24 patients similarly treated except
      for the infusion of the anti-LFA-1 antibody. No late rejection occurred. The T
      cell depletion method (E-rosetting or Campath IM plus complement) resulted in
      different rate of engraftment (83.3% v 57.9%, respectively, P = .05). Engraftment
      rate was slightly but not significantly influenced by the degree of HLA
      incompatibility between donor and recipient. Acute GVHD of grade II or more
      occurred in 35.5% of the patients and the rate of chronic GVHD was 12.9%. The
      overall actuarial survival rate with a functional graft is 47.3% with a mean
      follow-up of 28.0 months for patients with immunodeficiency and osteopetrosis,
      while none of the four patients with Fanconi's anemia survived. The development
      of full T-cell functions took on the average 6 months and of full B-cell
      functions 10 months. Significant infectious problems developed in the majority of
      the patients during the posttransplant course. Epstein-Barr virus-induced B-cell
      proliferative syndromes were observed in seven patients, six of whom had Wiskott
      Aldrich syndrome. Correction of immunodeficiency was comparable in terms of
      kinetics and quality with that observed in patients with severe combined
      immunodeficiency undergoing HLA-nonidentical BMT. Correction of osteopetrosis
      appears not to be different from what has been observed after HLA-identical BMT.
      The in vivo use of an anti-CD11a-LFA-1 antibody as an additional
      immunosuppressive therapy in HLA-nonidentical BMT may thus promote engraftment
      and survival with correction of the primary disease in a significant number of
      patients with life-threatening immunodeficiency and osteopetrosis, but not with
      Fanconi's anemia.

PMID- 1985692
TI  - Response rates and survival in primary systemic amyloidosis.
AB  - Patients (153) with biopsy-proven primary systemic amyloidosis (AL) were
      evaluated for their response rate to alkylating agent-based chemotherapy. Twenty
      seven of the patients (18%) responded. The serum creatinine concentration had an
      adverse effect on response rate (P = .05). In patients with nephrotic syndrome, a
      normal serum creatinine value, and no echocardiographic evidence of cardiac
      amyloidosis, the response rate was 39% (12 of 31). Five of 34 patients with
      amyloid cardiomyopathy responded. Two of these five are alive 10 years after
      diagnosis. None of the 18 patients with amyloid peripheral neuropathy showed
      regression of their disease. The median time to achieve response was 11.7 months.
      The median survival of the 27 patients was 89.4 months and 21 of 27 survived 5
      years (78%). Eight patients remain alive with a minimum follow-up of 90 months.
      Seven died of acute leukemia or dysmyelopoietic syndrome, a presumed complication
      of melphalan therapy. In the group of 126 patients who showed no response to
      alkylating agent-based therapy, the median survival was 14.7 months and 9 (7%)
      survived over 5 years. All 126 patients have died. Alkylating agent-based
      chemotherapy for AL is beneficial in a subset of patients and a trial of
      chemotherapy is strongly recommended. Those patients who do respond demonstrate
      survival benefit.

PMID- 1985694
TI  - Regulatory elements of the erythropoietin gene.
AB  - Because the human hepatoma cell line Hep3B produces erythropoietin (Epo) in a
      regulated fashion, it can be used to investigate the cis-acting regulatory
      elements of the Epo gene. Comparison of primate and mouse sequences shows strong
      homology not only in the coding sequence but also within the 5' flanking region,
      the first intron, and the 3' flanking region. These portions of the Epo gene were
      inserted 5' and 3' to a reporter gene, human growth hormone (GH). 5A is a 1,192
      base pair (bp) HindIII-Xbal fragment that extends from 378 bp 5' to the cap site
      through the first intron. To obviate the problem of false initiation of
      translation from the Epo ATG start codon, this site was changed to TAG by site
      directed mutagenesis. 3A is a 255-bp Accl-BglII fragment that extends 67 bp
      upstream from the Epo termination codon and covers most of the 3' noncoding
      region of homology. The plasmid DNAs were transfected by electroporation into
      Hep3B cells with RSVCAT as an internal standard to correct for transfection
      efficiency. One aliquot of cells was exposed to 50 mumol/L CoCl2 or to 1% O2. At
      the end of the incubations, GH and Epo were measured in the cell media and the
      cell pellet was assayed for CAT. Production of GH was stimulated 1.7-fold by
      cobalt or hypoxia. Furthermore, addition of 3A to the GH gene, irrespective of
      orientation, stimulated GH production 2.6-fold with CoCl2 and 2.3-fold with
      hypoxia. Stable cell lines were produced by cotransfection of the above
      constructions, along with the selectable marker pSV-Neo. In two clones, exposure
      to hypoxia resulted in much more marked (16-fold) induction of GH. Stimulus of
      both GH and Epo production by hypoxia was partially abrogated by carbon monoxide.
      These results demonstrate the presence of promoter and enhancer elements within
      the human Epo gene that are appropriately responsive to hypoxia and cobalt.

PMID- 1985693
TI  - Erythropoietin mRNA levels are governed by both the rate of gene transcription
      and posttranscriptional events.
AB  - The human hepatoma cell line, Hep3B, synthesizes large quantities of
      erythropoietin (Epo) mRNA and protein in a regulated manner in response to
      hypoxia and cobaltous chloride (CoCl2). To further understand the regulation of
      Epo gene expression, we studied the effects of hypoxia and CoCl2 on the rate of
      Epo gene transcription. While Northern blot analyses showed that steady-state Epo
      mRNA levels increase more than 50-fold in response to hypoxia or CoCl2, nuclear
      run-off experiments demonstrated only a 10-fold increase in Epo gene
      transcription in response to these stimuli. In the presence of either actinomycin
      D (Act D) or cycloheximide, the stability of biologically functional Epo mRNA was
      much greater than that observed in the absence of these agents and much greater
      than that which has been reported in vivo. These findings suggest that the
      stability of Epo mRNA is modulated by the transcription and translation of
      rapidly turning over gene product(s). Thus, Epo mRNA levels are determined by
      both the rate of gene transcription and posttranscriptional events. These
      experiments demonstrate a potential pitfall in estimating mRNA half-lives based
      on Act D chase experiments alone.

PMID- 1985695
TI  - Interleukin-6 mRNA and protein increase in vivo following induction of acute
      thrombocytopenia in mice.
AB  - Induction of experimental thrombocytopenia in rodents results in the enhancement
      of megakaryocytic growth and differentiation. Interleukin-3 (IL-3) and IL-6,
      cytokines with a broad spectrum of biologic activities, stimulate
      megakaryocytopoiesis in vitro. To determine if expression of these factors might
      increase in response to experimental thrombocytopenia, we measured steady-state
      levels of IL-3 and IL-6 mRNA following rabbit antiplatelet serum (APS) injection.
      Groups of mice were injected intravenously with 0.2 mL APS while control animals
      received rabbit antilymphocyte serum (ALS), normal rabbit serum (NRS), or
      phosphate-buffered saline (PBS). At various times up to 72 hours after injection
      mice were exsanguinated and splenectomized. Platelet counts in the experimental
      animals were less than 12% of controls. Splenic RNA was hybridized in solution to
      32P-UTP-labeled cRNA probes for IL-3 and IL-6. RNase-resistant hybrids were
      resolved on denaturing gels and visualized autoradiographically. IL-3 hybrids
      were undetectable at all time points tested, irrespective of the film exposure
      time or specific activity of the probe. Conversely, IL-6 hybrids were easily
      visualized and showed peak expression at 1.5 to 2.0 hours. By 3 hours, IL-6 mRNA
      had returned almost to the level of the controls. Similar results were observed
      in the bone marrow, although maximal IL-6 mRNA in that tissue was observed 4
      hours following APS administration. To determine if this mRNA increment was
      associated with a concomitant increase in bioactive protein, serum was tested for
      its ability to stimulate IL-6-dependent B9 cells. At 1.75 hours following
      injection, experimental animals showed a small but significant increment in IL-6
      activity compared with controls (200 +/- 30 U/mL IL-6 compared with 129 +/- 17
      U/mL in ALS-injected controls, 106 +/- 17 U/mL in NRS-injected controls and 84 +/
      17 U/mL in PBS-injected controls). The data show that IL-6 mRNA and bioactive
      protein increase in response to acute immunothrombocytopenia, while no increment
      in IL-3 is detectable. These results suggest that IL-6 may play a role in the
      physiologic response to acute immunothrombocytopenia.

PMID- 1985696
TI  - Retroviral transformation of cerebral microvascular endothelial cells: macrophage
      like and microvascular endothelial cell properties.
AB  - We report that L-cell-conditioned medium (LCM) transforms porcine cerebral
      microvascular (PCMV) endothelial cells into cells with macrophage-like
      properties. LCM is known to contain both cytokine(s) and the L-cell virus, a
      murine retrovirus found in the L929 cell and LCM. Our evidence suggests that both
      LCM cytokine(s) and the L-cell virus are involved in this PCMV endothelial cell
      transformation. Criteria for transformation include focus formation, decreased
      serum requirements for growth, changes in morphology including nonadherence,
      propagation in suspension culture, and a decreased growth response to stimulation
      with a known endothelial cell mitogen. Macrophage-like characteristics of this
      transformed cell, designated as RVTE, include pinocytosis of low-density
      lipoprotein, Fc receptor-mediated phagocytosis, phagocytosis of bacteria and
      zymosan, the expression of macrophage enzyme markers, and constitutive production
      of colony-stimulating factor 1. However, the transformed cell retains several
      properties of the nontransformed cell including the expression of FVIII:RAg and
      in vitro self-organization into capillary-like structures. Cloning of RVTE cells
      clearly shows that both macrophage-like and cerebral microvascular endothelial
      cell properties are present in the same cell. During self-organization,
      nontransformed cells express morphologic and functional characteristics
      classically associated with the macrophage. These findings suggest that some
      brain capillary pathophysiologies could involve macrophage-like cerebral
      microvascular endothelial cells. Furthermore, the "reticuloendothelial"
      phenotypic repertoire expressed by this transformed cerebral microvascular
      endothelial cell may show that the cerebral capillary endothelial cell in vivo is
      derived from a hematopoietic and/or phagocytic precursor.

PMID- 1985697
TI  - Fibrinogen is not synthesized by human megakaryocytes.
AB  - The origin of platelet fibrinogen is controversial. It may arise from two
      sources: (a) exogenously by endocytosis of plasma fibrinogen, or (b) endogenously
      by synthesis. We explored the second possibility because we previously
      demonstrated that the first mechanism does occur. Fibrinogen synthesis by human
      megakaryocytes (MK) was investigated by in situ hybridization and the polymerase
      chain reaction (PCR) applied to mRNA. MK differentiating from marrow CFU-MK were
      cultured in suspension. In situ hybridization using the 35S alpha and beta
      fibrinogen chain anti-sense riboprobes was totally negative in MK in comparison
      with negative controls (lambda phage and alpha and beta fibrinogen chain sense
      riboprobes). In contrast, synthesis of fibrinogen was detected by this technique
      in a hepatoma cell line (HepG 2). Furthermore, mRNA for alpha and beta chains of
      fibrinogen was not detected by the PCR performed on mRNA from cultured MK
      enriched to 90% purity, by the immunomagnetic bead technique, even after Southern
      blotting of the amplified products. In addition, fibrinogen mRNA was undetected
      in marrow MK and in platelets by the same technique, whereas a specific
      megakaryocyte gene transcript (GPIb alpha) was easily detected. These
      observations demonstrate that the only mechanism responsible for the presence of
      fibrinogen in platelets is endocytosis of fibrinogen from plasma.

PMID- 1985698
TI  - Molecular defect in coagulation factor XFriuli results from a substitution of
      serine for proline at position 343.
AB  - Our previous findings suggested that coagulation factor XFriuli could be
      functionally defective owing to a point mutation in the portion of the factor X
      gene coding for the fully activated heavy chain. To verify the existence of this
      postulated change, we analyzed all eight exons of the normal and Friuli factor X
      gene. Each exon was amplified from genomic DNA using the polymerase chain
      reaction and cloned into the plasmid pUC19. The amplified DNA inserts were
      subjected to direct sequencing by the dideoxy chain termination method with
      forward and reverse oligonucleotide sequencing primers. A point mutation (C to T
      transition at nucleotide position 19,297) that results in coding for serine (TCC)
      in place of proline (CCC) at amino acid position 343 was found. This substitution
      involves a highly conserved proline residue oriented spatially close to both the
      cleavage site of the zymogen and the active site of the enzyme and explains the
      previous observations of discrete biochemical and functional differences between
      factor XFriuli and normal factor X. The mutation abolished an HgiCI restriction
      site present in the normal factor X gene, and this change constitutes the basis
      for a convenient method for screening individuals carrying this molecular defect.
      Proline343 is in conserved region 5 of the serine protease superfamily to which
      factor X belongs and is part of a 14-residue L*****P******C motif that occurs in
      at least 16 other enzymes. Computer analysis suggests that the motif may be an
      essential aspect of conformational features important to functional properties of
      factor X as well as other serine proteases.

PMID- 1985699
TI  - Consistent involvement of the bcr gene by 9;22 breakpoints in pediatric acute
      leukemias.
AB  - To investigate the relationship of bcr-abl fusion mRNAs with childhood acute
      lymphoblastic leukemias (ALL), we examined 27 pediatric Philadelphia chromosome
      (Ph1)-positive acute leukemias using a reverse polymerase chain reaction (PCR)
      procedure. In cells from 24 leukemias, single bcr-abl PCR products were detected
      that corresponded to breakpoints in the minor breakpoint cluster region (mbcr in
      intron 1 of the bcr gene) associated with production of the P190 fusion protein.
      Cells from the three remaining leukemias contained breakpoints in the major
      breakpoint cluster region (Mbcr) as shown by PCR and Southern blot analyses.
      These three leukemias also contained low levels of the mbcr PCR product that may
      have resulted from alternative splicing of the bcr-abl precursor RNA. A screen of
      35 additional leukemias from patients who failed therapy before day 180
      (induction failures or early relapses) found one case with unsuccessful
      cytogenetics to express Mbcr-abl RNA. All four children with Mbcr breakpoints had
      white blood cell levels in excess of 250,000 at presentation (compared with 2 of
      24 with mbcr breakpoints) and two had hematologic and clinical features
      suggestive of chronic myelogenous leukemias (CML) in lymphoid blast crisis. Our
      results indicate that in Ph1-positive pediatric leukemias, all 9;22 breakpoints
      occur in one of the two known breakpoint cluster regions in the bcr gene on
      chromosome 22. The reverse PCR reliably detected all patients with cytogenetic
      t(9;22) and is capable of detecting additional Ph1-positive leukemias that are
      missed by standard cytogenetics. Furthermore, the Mbcr-type breakpoint,
      associated with production of p210, can be seen in childhood leukemias presenting
      either as clinical ALL or as apparent lymphoid blast crisis of CML, suggesting
      that t(9;22) breakpoint locations do not exclusively determine the biologic and
      clinical features of pediatric Ph1-positive ALL.

PMID- 1985700
TI  - Anti-CD33 monoclonal antibody and etoposide/cytosine arabinoside combinations for
      the ex vivo purification of bone marrow in acute nonlymphocytic leukemia.
AB  - Pharmacologic and immunologic methods of ex-vivo bone marrow (BM) purging for
      acute nonlymphocytic leukemia (ANLL) were combined to augment the effect of
      either method alone. Etoposide (VP16; 20 to 30 micrograms/mL) with or without
      cytosine arabinoside (Ara C; 10 mg/mL) was used in tandem with the anti-CD33
      monoclonal antibody (MoAb), MY9, chosen because CD33 is found on the stem cell
      pool in the majority of patients with ANLL. The agents were tested singly or
      sequentially, with a 1-hour incubation of the drugs preceding complement-mediated
      lysis using MY9. VP16 combined with Ara C killed up to 3.9 +/- 0.3 and 5.11 +/-
      0.4 logs of the human ANLL cell lines HL60 and K562 at drug concentrations that
      killed only 1.2 +/- 0.1 logs of normal committed granulocyte/macrophage stem
      cells (CFU-GM). Adding a single exposure of the MY9 and complement (C') to the
      drug-treated cells, greater than 5.4 logs of HL60 were killed. Similar to other
      pharmacologic agents, no differential kill for clonagenic leukemic cells (colony
      forming unit-leukemia; CFU-L) from patients with ANLL was seen for drug only
      treated blasts versus normal CFU-granulocyte-macrophage (CFU-GM), with less than
      1 log CFU-L kill at drug concentrations that spared 1 log of CFU-GM. Similarly,
      only 1.1 +/- 0.3 logs of ANLL CFU-L were eliminated using MY9 and C'. However,
      with the sequential VP16/Ara C----MY9 + C' treatment, synergy was demonstrated
      and 2.6 +/- 0.3 logs of CFU-L were eliminated. Because CD33 is also found on the
      normal CFU-GM pool, two-stage long-term BM cultures were performed to determine
      pluripotent stem cell elimination by the drug/MoAb purging combination. No
      difference of CFU-GM or BFU-E production at 4 to 6 weeks of culture for VP16/Ara
      C, MY9 + C', or VP16/AraC----My9 + C' treated cells was seen compared with
      untreated controls indicating sparing of early progenitor cells. Sequential ex
      vivo treatment of human ANLL CFU-L with VP16/Ara C followed by complement
      mediated lysis using MY9 synergistically kills CFU-L while sparing early normal
      hematopoietic progenitor cells, and thus may be a more effective way to purge BM
      than either alone.

PMID- 1985701
TI  - Signal transduction and the regulation of actin conformation during myeloid
      maturation: studies in HL60 cells.
AB  - Maturation of human myeloid cells is associated with quantitative and qualitative
      changes in protein kinase C (PKC) and increases in N-formyl-L-methionyl-L-leucyl
      L-phenylalanine (FMLP) receptors, actin, and actin regulatory proteins. We have
      studied the actin responses and cell shape changes caused by FMLP and its second
      messenger pathways in HL60 cells undergoing neutrophilic maturation. In uninduced
      cells, the PKC activators 12-O-tetradecanoyl phorbol-13-acetate (TPA),
      bryostatin, and 1-oleyl-2-acetylglycerol (OAG) resulted in 15% to 30% decreases
      in F-actin, whereas FMLP had no effect. Ionomycin had no effect on actin but did
      cause a 10-fold increase in intracellular calcium. Cells grown for 24 hours in 1%
      dimethyl sulfoxide (DMSO) acquired the ability to polymerize actin in response to
      FMLP and ionomycin. TPA continued to cause a decrease in F-actin at 24 hours, but
      caused an increase in F-actin at 48 to 72 hours of maturation. The PKC inhibitor
      1-5-isoquinolinesulfonyl 2-methylpiperazine (H7) partially blocked the F-actin
      increase caused by TPA in induced cells, but had no effect on the decrease in F
      actin caused by TPA in uninduced cells or the increase in F-actin seen in FMLP
      treated neutrophils. F-actin rich pseudopods developed following TPA or FMLP
      stimulation of induced HL60 cells; in uninduced cells neither agent caused
      pseudopod formation but TPA caused a dramatic loss of surface ruffles. The
      ability of FMLP and ionomycin to elicit a neutrophil-like actin response in HL60
      cells within 24 hours after DMSO treatment shows that the actin regulatory
      mechanism is mature by that time. The inability of ionomycin to increase F-actin
      in uninduced cells supports the view that calcium increases alone are
      insufficient for actin polymerization. The longer maturation time required for
      HL60 cells to develop an actin polymerization response to TPA compared with FMLP,
      coupled with the inability of H7 to block the FMLP-mediated F-actin increase in
      neutrophils, suggests that the F-actin increase caused by FMLP is not mediated
      solely by PKC. Lastly, the TPA-induced F-actin decrease and shape changes in
      uninduced HL60 cells, and the longer time required for a "mature" response to
      TPA, may reflect immaturity in the PKC isoenzyme pattern rather than immaturity
      of the actin regulatory mechanism.

PMID- 1985702
TI  - Hemoglobin Cagliari (beta 60 [E4] Val----Glu): a novel unstable thalassemic
      hemoglobinopathy.
AB  - This report describes a patient with thalassemia intermedia-like phenotype born
      to normal parents in whom globin gene sequencing detected a novel abnormal
      hemoglobin (Hb) due to a T to A substitution at codon 60 of the beta-globin gene
      arising as a de novo mutation. Normal sequences were detected at the homologous
      beta-globin locus. This mutation results in the substitution of a polar (glutamic
      acid) for a nonpolar (valine) residue near the corner of the heme pocket of the
      beta-globin chain. The novel variant has been designated Hb Cagliari, from the
      place of birth of the propositus. Kinetics of globin synthesis performed
      following splenectomy suggest that this new Hb variant is synthesized at a near
      normal rate but undergoes rapid breakdown. The extreme lability of the variant
      explains the clinical and hematologic picture characterized by marked ineffective
      erythropoiesis, thalassemia-like bone changes, iron overload, high proportion of
      Hb F in the peripheral blood, reduced beta/alpha-globin chain synthesis ratio in
      peripheral blood reticulocytes, and absence of the abnormal Hb in peripheral
      blood at extensive protein structural analysis before splenectomy. This case
      indicates that a thalassemic hemoglobinopathy should be suspected in the presence
      of a patient with a thalassemia intermedia-like phenotype born to normal parents,
      even when protein structural analysis fails to detect an abnormal Hb. DNA
      sequencing may allow to define the mutation, thus making the proper diagnosis.

PMID- 1985703
TI  - High doses of intravenous Ig inhibit in vitro uptake of C4 fragments onto
      sensitized erythrocytes.
AB  - We have recently reported that intravenous Ig (IVIg) inhibits uptake of activated
      C3 fragments onto antibody-sensitized red blood cells (RBCs). To elucidate the
      mechanism by which IVIg exerts its effect on the complement system, we examined
      the possible interference with the C4 step of the classical complement cascade.
      We examined the capacity of autologous serum containing high concentrations of
      human IVIg to deposit C4 fragments onto model targets (guinea pig and/or human
      erythrocytes sensitized with rabbit anti-guinea pig/human erythrocytes IgG
      antibody). C4 binding was quantified with radiolabeled anti-C4. Guinea pig serum
      with added IVIg suppressed C4 uptake onto IgG-sensitized guinea pig erythrocytes
      at all time points (0, 5, 15, and 30 minutes). Using sera of guinea pigs treated
      with increasing doses of IVIg, this effect was shown to be dose-responsive. Serum
      from a patient treated with IVIg showed reduced C4 uptake onto sensitized
      homologous RBCs. In comparison with the serum from the same patient before IVIg
      therapy was administered, levels were decreased almost to background. C4
      functional titers in those two samples were not different. C3 uptake was studied
      in parallel with C4 to compare the degree of inhibition using sera with
      increasing doses of IVIg in both the human and guinea pig system. C3 and C4
      inhibition curves completely overlapped. Our findings suggest that IVIg is an
      effective inhibitor of deposition of early complement activation products (C4b,
      C3b) onto target surfaces and may indicate interference of IVIg with multiple
      sites of complement activation.

PMID- 1985704
TI  - Increased levels of soluble interleukin-2 receptors and tumor necrosis factor in
      serum of patients with myelodysplastic syndromes.

PMID- 1985705
TI  - Variability in DNA measurements in multiple tumor samples of human colonic
      carcinoma.
AB  - The DNA ploidy and cell-cycle distribution of three separate fresh tissue samples
      of 60 colorectal adenocarcinomas were analyzed by flow cytometry. DNA ploidy was
      concordant among the three samples in 38 cases (63.3%). In the remaining 22 cases
      (36.6%), the DNA histograms of two of the three multiple samples were similar;
      however, the ploidy of the third sample was discordant. No relationship was
      observed between Dukes' stage and histologic grade with concordance or
      discordance among samples. Thus, in about one third of the colonic carcinomas, a
      single sample showing either a diploid or diploid-cycling DNA histogram would not
      detect aneuploid DNA patterns. Comparison of scrapes and fine-needle aspirates of
      tumors as alternative sampling methods of tumors for DNA ploidy analysis
      indicated a strong association with the tumor ploidy (84% and 96%, respectively)
      only when the ploidy of the multiple samples was concordant. In about 25% of the
      cases, tumor scrapes and fine-needle aspirates did not correlate with the "most
      abnormal" ploidy observed in one of the three tissue samples. The data suggest
      that single or even double tissue samples may not show aneuploid DNA patterns in
      a substantial proportion of colorectal cancers.

PMID- 1985706
TI  - Clear cell carcinoma of the inguinal region arising from endometriosis.
AB  - The second and third examples of clear cell carcinoma of the inguinal region
      arising from endometriosis are reported. In one patient a right inguinal mass was
      excised along with an inguinal lymph node dissection. The tumor recurred in the
      retroperitoneum and was removed, and postoperative radiation therapy was
      administered. The patient died of recurrent tumor after 11 years. The other
      patient was treated by excision of a left inguinal mass and an inguinal lymph
      node dissection and was alive without recurrence 4 years and 8 months later.

PMID- 1985707
TI  - Cytogenetic evidence of clonality in a case of pigmented villonodular synovitis.
AB  - Pigmented villonodular synovitis is an uncommon benign lesion that is
      characterized by diffuse synovial proliferation. Based on animal models, this
      lesion has been conjectured previously to be reactive in nature. In this report,
      the authors present the histologic and cytogenetic findings for a pigmented
      villonodular synovitis that was excised from the right knee of a 47-year-old man.
      Trisomy 7 was observed in 24 of 75 (35%) metaphases obtained from short-term
      culture of cells from this tumor. These findings suggest that some cases of
      pigmented villonodular synovitis represent clonal, neoplastic proliferations.

PMID- 1985708
TI  - Percent tumor necrosis as a predictor of treatment response in canine
      osteosarcoma.
AB  - The percent tumor necrosis was determined in 200 dogs with spontaneously
      occurring osteosarcoma. One hundred dogs had no treatment before amputation or
      death. One hundred other dogs were treated with either radiation therapy alone (n
      = 23), intraarterial (IA) cisplatin alone (n = 16), intravenous (IV) cisplatin
      alone (n = 6), radiation therapy plus IA cisplatin (n = 47), or radiation therapy
      plus IV cisplatin (n = 8). Eighty-nine of these 100 dogs had their tumors
      resected 3 weeks after the end of therapy (6 weeks after the initiation of
      therapy) and replaced with a cortical bone allograft. Dogs with preoperative
      treatment were evaluated for local tumor control and time to metastasis. The mean
      percent tumor necrosis in untreated osteosarcoma was 26.8%. The mean percent
      tumor necrosis for dogs receiving radiation only, IA cisplatin only, and IV
      cisplatin only was 81.6%, 49.1% and 23.8%, respectively. The mean percent tumor
      necrosis for dogs receiving radiation therapy plus IA cisplatin or radiation
      therapy plus IV cisplatin was 83.7% and 78.2%, respectively. There was no
      significant difference between percent tumor necrosis in untreated osteosarcoma
      compared with those receiving IV cisplatin, but there was a significant increase
      in percent tumor necrosis with all other treatments. A mathematic model for the
      effect of cisplatin and radiation dose was developed using multiple regression
      analysis. The radiation dose calculated to cause at least 80% tumor necrosis was
      42.2 Gy (95% confidence interval [CI], 38.0 to 47.6 Gy) when radiation was given
      alone and 28.1 Gy (95% CI, 21.3 to 36.6 Gy) when radiation was combined with IA
      cisplatin. Areas of viable tumor tended to be most frequent adjacent to the
      articular cartilage and in the joint capsule. Percent tumor necrosis was strongly
      predictive for local tumor control; 28 of 32 dogs with greater than 80% tumor
      necrosis had local control, and only eight of 29 dogs with less than 79% tumor
      necrosis had local control (P = 0.0047). There was no correlation between percent
      tumor necrosis and time to metastasis.

PMID- 1985709
TI  - Usefulness of serum glycoconjugates in precancerous and cancerous diseases of the
      oral cavity.
AB  - Sera from 47 healthy controls, 18 normal individuals with the habit of tobacco
      chewing, 43 patients with oral precancerous (PC) conditions, and 40 patients with
      oral cancer (OC) were studied for the levels of total sialic acid (TSA), lipid
      bound sialic acid (LSA), mucoid proteins, and protein-bound hexoses (PBH)
      (galactose and mannose). The changes in the glycoconjugate levels were
      insignificant between the controls and the normal tobacco chewers. All four
      parameters were significantly elevated in oral PC patients compared with
      controls. The levels of PBH and LSA showed significant increase in the oral PC
      patients compared with the normal tobacco chewers. A significant increase was
      observed in the levels of TSA, LSA, mucoid proteins, and PBH in OC patients
      compared with controls, normal tobacco chewers, and patients with oral PC.
      Increasing levels of all the biomarkers were found with progression of the
      malignant disease. Elevations in the levels of TSA and LSA were statistically
      significant in Stage IV patients compared with Stage III patients. The patients
      with metastases had higher levels of the biomarkers than the patients with
      primary OC. However, elevations only in LSA levels were statistically
      significant. These results suggest that evaluations of the serum glycoconjugate
      levels may be useful in diagnosis of the patients with oral PC or OC. In addition
      to their value in early detection, they can also help in staging of the disease.

PMID- 1985710
TI  - A prospective randomized comparison of protracted infusional 5-fluorouracil with
      or without weekly bolus cisplatin in metastatic colorectal carcinoma. A Mid
      Atlantic Oncology Program study.
AB  - One hundred eighty-four patients with advanced measurable colorectal cancer not
      previously treated with chemotherapy were entered into a prospective randomized
      clinical trial by the Mid-Atlantic Oncology Program (MAOP) to assess the value of
      weekly cisplatin (20 mg/m2) when added to a protracted schedule of 5-fluorouracil
      (5-FU) infusion (PIF) at 300 mg/m2/d for 10 weeks of every 12 weeks. The liver
      was the primary indicator lesion in approximately 75% of the study group. All
      tumor measurements required radiographic confirmation. The response rate in the
      PIF alone arm was 35% (29 of 83; 95% confidence interval [CI], 25% to 46%)
      compared with 33% (28 of 85; 95% CI, 23% to 44%) for the arm in which weekly
      cisplatin was added to PIF. The median survival times were 11.8 and 11.2 months
      in the two groups. Weekly cisplatin does not appear to add to the effectiveness
      of PIF in colorectal carcinoma.

PMID- 1985711
TI  - Relationship between histologic features, DNA flow cytometry, and clinical
      behavior of squamous cell carcinomas of the larynx.
AB  - Flow cytometric analysis of DNA content was done on 133 primary squamous cell
      carcinomas of the larynx. Overall, 76 tumors (57.1%) were not diploid (aneuploid
      or tetraploid). The DNA index (DI) was calculated and grouped into three levels.
      Fifty-seven cases had a DI in a range of 1.85 to 2.15 (44 diploid and 13
      tetraploid). The cases were grouped in relation to ploidy, proliferative index,
      and the tumor-node-metastasis (TNM) system. Every group was analyzed with respect
      to survival rate. Ploidy was related to histocytologic grade. In well
      differentiated tumors (G1) survival rates at 48 months were 41.7% in diploid
      cases and 27.7% in nondiploid ones (relative risk [RR], 2.01; 95% confidence
      interval [CI], 0.89, 4.52). In NO cases that underwent surgery, survival rates at
      48 months were, respectively, 81.8% and 49.2% (RR, 5.07; 95% CI, 0.76, 33.93).
      These results suggest that ploidy may be a new independent parameter of prognosis
      in squamous cell carcinoma of the larynx. This is useful in clinical practice
      because it allows the clinician to recognize those cases with poorer prognosis
      among the early tumors at a stage where other prognostic parameters are not yet
      available.

PMID- 1985712
TI  - Chondrosarcomas of the synovium.
AB  - Chondrosarcoma of the synovium, either primary or secondary to synovial
      chondromatosis, is rare. Ten cases of synovial chondrosarcoma were studied (four
      from the Mayo Clinic files and six from the authors' consultation files). Two
      were considered primary. In five cases there was evidence of preexisting synovial
      chondromatosis, and in the remaining three, there was a suggestion of preexisting
      disease. Several histologic features were found that were helpful to diagnose
      malignancy. The most important ones were loss of the "clustering" growth pattern
      typical of synovial chondromatosis, myxoid change in the matrix, areas of
      necrosis, and spindling at the periphery of chondroid lobules. Pulmonary
      metastasis developed in five of nine patients; three of these patients died.

PMID- 1985713
TI  - Prognostic value of histopathology in Ewing's sarcoma. Long-term follow-up of
      distal extremity primary tumors.
AB  - The pathologic material from 56 patients diagnosed initially as Ewing's sarcoma
      of the distal extremity and treated on National Cancer Institute protocols
      between 1968 and 1984 was reviewed and correlated with clinical outcome.
      Histologically, the tumors were categorized, based on recent pathologic criteria,
      into three diagnostic groups: (1) typical Ewing's sarcoma, (2) atypical Ewing's
      sarcoma, and (3) other (predominantly peripheral neuroepithelioma [PN]). Thirty
      two patients (57%) had typical Ewing's, 13 (23%) were atypical, and 11 (20%) were
      in the "other" diagnostic category (seven [13%] PN, two primitive
      rhabdomyosarcoma, one primitive sarcoma of bone, and one synovial cell sarcoma).
      No cases of metastatic neuroblastoma, osteosarcoma, or lymphoma were found. Forty
      five patients had localized disease at diagnosis; 11 had metastases. Patients
      with typical Ewing's sarcoma were less likely to have metastatic disease at the
      time of diagnosis. Only two of 32 patients with typical Ewing's sarcoma had
      metastases compared with nine of 24 patients in the two other groups. The pattern
      of relapse was also different in these other groups compared with typical Ewing's
      patients; five patients developed lymph node metastases and two patients
      developed brain metastases. Although the presence of metastatic disease at
      diagnosis was a strong negative prognostic factor, our histologic grouping was
      independently prognostic of clinical outcome in patients with localized disease.
      Patients with typical osseous Ewing's sarcoma had an improved overall survival
      (P2 = 0.03) and patients with other tumors (neither typical nor atypical Ewing's
      sarcoma) had a poorer disease-free survival (P2 = 0.02). Since no generally
      accepted histopathologic prognostic criteria exist for Ewing's sarcoma, the
      potential value of our proposed classification should be evaluated in a larger
      retrospective and a prospective study.

PMID- 1985714
TI  - Acinic cell carcinoma. Clinicopathologic review.
AB  - The authors reviewed 90 cases of acinic cell carcinoma treated at the Mayo Clinic
      to assess long-term follow-up and to study features predictive of disease
      progression. Sixty-three patients (55 females and 35 males) were seen for primary
      treatment; 27 had recurrent disease when first evaluated. Histologically, these
      tumors were composed of serous acinar cells and intercalated duct-type cells.
      Morphologic patterns included solid, microcystic, follicular, and papillary
      cystic. All patients were followed for at least 10 years or until death. Of the
      primary treatment group, 44% had local recurrence, 19% had metastasis, and 25%
      died of disease. Disease first recurred locally up to 30 years after presentation
      and resulted in death after as many as 38 years. Poor prognostic features include
      pain or fixation; gross invasion; microscopic features of desmoplasia, atypia, or
      increased mitotic activity; and excision as initial treatment. Neither
      morphologic pattern nor cell composition was a predictive feature.

PMID- 1985715
TI  - Risk factors for cancer of the tongue in Uruguay.
AB  - From 1987 to 1989, a hospital-based case-control study of cancer of the tongue
      was conducted in Montevideo, Uruguay, as part of a large study to investigate a
      number of risk factors for cancer of the oral cavity, pharynx, and larynx. The
      study involved interviews with 57 cases and 353 controls and was restricted to
      men. Relative risks (RR) associated with tobacco smoking, alcohol drinking, and
      selected dietary items were obtained by unconditional logistic-regression
      analysis. Users of black tobacco had a RR fourfold higher than users of blond
      tobacco, and heavy drinkers of alcohol had a RR of 11.6. Infrequent consumption
      of vegetables was associated with a significant RR of 5.3, and heavy drinkers of
      the local infusion "mate" had a RR of 2.5. It was concluded that black tobacco
      smoking and alcohol drinking were the strongest risk factors for cancer of the
      tongue in Uruguay. Their effects combine according to a multiplicative model.
      Also, infrequent vegetable intake and mate ingestion contribute to the risk of
      cancer of the tongue.

PMID- 1985716
TI  - Bone sarcomas as second malignant neoplasms following childhood cancer.
AB  - This study explores the relationship between histologic variants of bone sarcomas
      and previous therapy in patients in whom an unrelated malignant neoplasm had been
      diagnosed during childhood. Sarcomas of bone were the most common second
      malignant neoplasm (SMN) reported to the Late Effects Study Group, a 13
      institution consortium consisting of pediatric oncology centers from western
      Europe, Canada, and the United States. The authors attempted to relate the
      histologic subtypes of the 91 bone tumors to clinical factors such as previous
      therapy and genetic predisposition because morphologic variants have been shown
      to have biologic significance in other tumors and may have etiologic import. The
      literature concerning the subtypes of bone tumors, clinical and experimental, is
      also reviewed. The authors also investigated the effect of several factors on the
      time interval from the first diagnosis to the SMN (i.e., the bone sarcoma).
      Anthracyclines significantly shortened the interval by about 3 years. The primary
      diagnosis also significantly affected the interval, with leukemia/lymphomas
      having the shortest interval and retinoblastoma the longest. The authors could
      not demonstrate any significant relationship between morphologic characteristics
      of the osteosarcoma and predisposing conditions. However, lesions diagnosed as
      chondrosarcoma and malignant fibrous histiocytoma occurred almost exclusively in
      patients who had received radiation therapy to the site in which the SMN
      developed.

PMID- 1985717
TI  - A Southwest Oncology Group study on the use of a human tumor cloning assay for
      predicting response in patients with ovarian cancer.
AB  - A total of 211 patients with epithelial ovarian cancer (168 with tumors
      refractory to prior chemotherapy and 43 with no prior chemotherapy) from 33
      different Southwest Oncology Group institutions had their tumors sampled and
      specimens shipped to two central laboratories for drug-sensitivity testing in a
      human tumor cloning assay. The 168 patients with a prior history of chemotherapy
      failure (median of four prior chemotherapeutic agents) were treated with the most
      effective agent(s) found in the cloning assay (23 patients), and those patients
      whose tumors did not form colonies in vitro or did not manifest any sensitivity
      to agent(s) were treated with a clinician's choice of agent(s) (101 patients).
      The remaining 44 of the 168 patients were not treated with chemotherapy because
      of deteriorating performance status or early death. The complete and partial
      response rate in patients treated according to assay results was 28% versus 11%
      for the patients treated according to clinician's choice (P = 0.03). There was no
      statistically significant difference in survival between the two options (6.25
      versus 7 months, respectively). The 43 patients with no history of prior
      chemotherapy were all treated with standard combination chemotherapy, and their
      clinical response was compared with their in vitro sensitivity to the same
      agents. Overall there was a 100% true-positive rate and 100% true-negative rate
      for the seven evaluable patients. From these data the authors conclude that use
      of the human tumor cloning assay may increase the response rate but not the
      survival for selected patients with advanced chemotherapy-refractory ovarian
      cancer. The study is weakened, however, by the many steps of patient selection
      necessitated by inadequate tumor colony formation in vitro and the inability to
      treat all patients (because of early death or a rapid decline in performance
      status). The assay does appear to be worthy of additional study for predicting
      response to combination chemotherapy in patients without a prior history of
      chemotherapy. Finally the use of central chemosensitivity testing laboratories is
      feasible for testing in vitro predictive assays in a cooperative group setting.

PMID- 1985718
TI  - Yield from total skin examination and effectiveness of skin cancer awareness
      program. Findings in 874 new dermatology patients.
AB  - The authors reviewed 874 dermatology charts to assess the acceptance rate of
      total skin examination (TSE), incidental skin findings, and patient compliance
      regarding treatment recommendations. Of the 874 new dermatology patients studied,
      707 (80.9%) agreed to TSE. Important incidental findings were found in 151
      (21.4%). These included: (1) biopsy specimen-confirmed malignant tumors
      (malignant melanoma, lentigo maligna, and basal cell and squamous cell carcinoma)
      in 24 of the 707 patients (3.4%), (2) biopsy specimen-confirmed premalignant
      tumors (actinic keratosis with dysplasia, Bowenoid actinic keratosis, Bowenoid
      papulosis, and lentigo with dysplasia, in five (0.7%), (3) clinically diagnosed
      premalignant actinic keratosis in 64 (9.1%), (4) biopsy specimen-confirmed
      dysplastic nevi in 17 (2.4%), and (5) congenital nevi in 41 (5.8%). Only 4.2% of
      the patients returned for a yearly TSE, and only 6.0% were found to follow all
      recommendations for monthly self examination, yearly professional examination,
      and sun protection. It is concluded that TSE for all new patients, and on a
      yearly basis for all return patients, is valuable in the detection of many skin
      conditions and allows skin cancer screening to be done, since patients for the
      most part do not follow recommendations for at-home screening.

PMID- 1985719
TI  - Achievement of life goals by adult survivors of modern treatment for childhood
      cancer.
AB  - To assess the impact of the diagnosis and modern treatment of childhood cancer on
      achievement of adult goals, the authors evaluated employment, health and life
      insurance coverage, marriage, divorce, and reproduction in 227 former pediatric
      cancer patients. Each area was evaluated in relation to a common set of disease
      and demographic factors that included age at follow-up, age at diagnosis, gender,
      marital status, history of disease recurrence, and diagnosis. Patients were
      younger than 20 years of age at diagnosis, and their diagnoses were made between
      January 1, 1960, and December 31, 1984. The median age at diagnosis was 11.4
      years, and the median age at follow-up was 26.6 years. The percentage of
      unemployed male respondents did not differ from population norms. The percentage
      of unemployed female respondents, however, was slightly higher than that of the
      United States population. Approximately 11% of the survivors reported some form
      of employment-related discrimination, a level significantly lower than that of
      prior reports. Company-offered health insurance was provided to 92.4% of full
      time and 90.0% of part-time employed respondents. Life insurance was purchased by
      60% of full-time employed men and 55% of women. These percentages were lower than
      those reported for the United States population. Twenty-four percent of those
      with life insurance had difficulty obtaining it. Fifty-eight percent of the
      subjects were married or lived as married. The percentages of married men and
      women were significantly lower than United States norms. Twenty percent of those
      who were married or lived as married have divorced or separated or no longer live
      as married. Women aged 20 to 24 years were less likely to marry, and women aged
      35 to 44 years had a significantly higher frequency of divorce than similarly
      aged United States women. In general, the history of childhood cancer did not
      influence the decision to marry or live as married but was occasionally (20%)
      important in the decision to dissolve a marital relationship. Many former
      patients indicated that their diagnosis and treatment for childhood cancer
      influenced their decision to have children. The current study suggests that most
      former pediatric cancer patients achieve adult life goals. Additional research is
      necessary to define those populations at greatest risk of failure to achieve
      these goals.

PMID- 1985720
TI  - A study of cyproheptadine in the treatment of metastatic carcinoid tumor and the
      malignant carcinoid syndrome.
AB  - Sixteen patients with metastatic neuroendocrine tumors and the malignant
      carcinoid syndrome were treated with cyproheptadine (Periactin, Merck, Sharp &
      Dohme, West Point, PA) at maximum tolerable doses that ranged from 12 to 48 mg
      daily. Usual side effects were mild sedation and dry mouth, but three patients
      found it impossible to sustain treatment due to nausea and vomiting. Most
      patients had significant relief of diarrhea, frequently associated with weight
      gain. Relief of flushing was uncommon. The therapeutic benefit produced by
      cyproheptadine would appear to be a peripheral effect because 5
      hydroxyindoleacetic acid (5-HIAA) excretion in these patients was not reduced.
      Although there have been case reports of objective tumor regression with
      cyproheptadine therapy, this was not observed in any of these 16 patients.
      Cyproheptadine would appear to be a useful therapeutic tool for the management of
      diarrhea associated with the malignant carcinoid syndrome. An appropriate initial
      total daily dose is 0.4 mg/kg divided in three fractions with prompt modification
      to produce minimal and tolerable side effects.

PMID- 1985722
TI  - Prolonged response to carboplatin in an infant with brain stem glioma.
AB  - Adults and children with brain stem gliomas have a mean survival time of 15
      months after radiation therapy (XRT). Infants with this tumor present additional
      complexities for treatment because of possible neurotoxicity of the radiation to
      the developing brain. We report a 15-month-old child with biopsy-proven brain
      stem glioma with clinical and radiographic evidence of disease progression. She
      was treated with 24 monthly courses of carboplatin without radiation therapy and
      has had a 39+ month response. The clinical response started after 3 months and
      the radiographic evidence was documented at 10 months by magnetic resonance
      imaging. The toxicity was minimal. Longitudinal neuropsychological assessment
      demonstrated continued improvement at 36 months post diagnosis but with some
      motor functioning below expected age levels. Cervico-medullary astrocytoma in a
      young patient may be the appropriate clinical setting for future trials of
      chemotherapy without XRT.

PMID- 1985721
TI  - Remission induction and continuation therapy in children with their first relapse
      of acute lymphoid leukemia. A Pediatric Oncology Group study.
AB  - Between January 1979 and April 1983, 113 children undergoing their first relapse
      of acute lymphoid leukemia (ALL) at any site were registered in Pediatric
      Oncology Group study 7834; 98 were eligible and evaluable. In addition to
      radiotherapy administered to sites of local relapse, induction consisted of
      vincristine, doxorubicin, and prednisone (VAP) chemotherapy. Continuation therapy
      consisted of triple-drug intrathecal therapy and regimens of 6-thioguanine and
      cytarabine alternating with vincristine, prednisone, cyclophosphamide, and
      cytarabine. Randomization in continuation was between VAP pulses or no pulse,
      regardless of the site of relapse. This report provides long-term follow-up of
      these patients. Thirty-two of 39 children with bone marrow involvement achieved a
      complete response (CR). Only one of these is alive in an unmaintained remission,
      a child who did not have an initial CR. Thirty-four of 36 evaluable children with
      central nervous system involvement as the site of relapse achieved CR. Of these
      ten are alive; eight are in continuing CR. Nineteen of 20 boys with testicular
      relapse achieved CR. Of these, 14 are still alive and not receiving therapy,
      although only one half received treatment in compliance with the protocol
      described. These results illustrate the possibility of cure of patients who have
      relapsed with ALL when it is (1) confined to a meningeal or gonadal site and (2)
      treated vigorously with radiotherapy and a new regimen of systemic chemotherapy.
      The results reconfirm the need to prevent an initial relapse at any site.

PMID- 1985723
TI  - Postoperative follow-up of patients with early breast cancer. Patterns of care
      among clinical oncologists and a review of the literature.
AB  - Eighty clinical oncologists in the southeastern United States were surveyed to
      determine their strategies for follow-up care after primary treatment of early
      stage breast cancer. The frequency of use of the history and physical
      examination, complete blood count, liver function tests, carcinoembryonic antigen
      levels, chest x-ray, skeletal survey, bone scan, liver scan, and mammogram for
      observing hypothetical low- and high-risk patients was assessed. Yearly
      mammograms were recommended by more than 95% of respondents. History and physical
      examination were the modalities used most often, whereas periodic bone and liver
      scans were used only in a minority of patients. A review of the literature
      supported the strategy of the respondents in this survey and further underscored
      the cost-effectiveness of the history and physical examination in detecting
      recurrence during follow-up. Based on this survey and supporting literature,
      recommendations for reasonable yet cost-conscious follow-up are presented.

PMID- 1985724
TI  - Imaging of a parapharyngeal hemangiopericytoma. Radioimmunoscintigraphy (SPECT)
      with indium-111-labeled anti-CEA antibody, and comparison to digital subtraction
      angiography, computed tomography, and immunohistochemistry.
AB  - A 27-year-old male patient with a parapharyngeal hemangiopericytoma was
      investigated radiologically with orthopantomography, computed tomography, and
      digital subtraction angiography before the operation. Because a malignancy was
      suspected, the patient was imaged with gamma camera using radiolabeled monoclonal
      anticarcinoembryonal antigen antibody including single photon emission computed
      tomography. The radioantibody accumulated strongly into the neoplasm. Tumor to
      background ratio was 2.2. Samples of the excised tumor were stained
      immunohistochemically for desmin, vimentin, muscle actin, cytokeratin, CEA
      (carcinoembryonic antigen), and factor VIII. They showed that the antibody uptake
      was of unspecific nature and not due to CEA expression in the tumor.

PMID- 1985725
TI  - Elective radical neck dissection in epidermoid cancer of the head and neck. A
      retrospective analysis of 853 cases of mouth, pharynx, and larynx cancer.
AB  - A retrospective analysis of 853 patients with cancer of the mouth, pharynx, and
      larynx operated on over a 30-year period was performed. Four hundred fifty-seven
      of them had a radical neck dissection (RND) at some point. Five hundred ninety
      patients had no clinically positive nodes (N-o) necks at the time of primary
      treatment; 99 of these had elective neck dissection, whereas 95 others had a
      delayed RND when nodes became clinically involved. Twenty-three percent of all N
      o patients had microscopically involved nodes and less than half of these were
      among those patients selected for elective RND. Furthermore, 58% of those
      patients who had elective RND did not have positive nodes. Comparative analysis
      of elective RND, delayed therapeutic RND after clinical appearance of nodes, and
      composite operations for patients with N1-N3 disease indicates little difference
      in disease-free survival when the nodes in the elective RND were positive
      microscopically for tumors (56%, 49% and 47% respectively). It thus seems that
      elective RND offers no real advantage over a careful watchful waiting approach in
      most patients.

PMID- 1985726
TI  - Diagnostic sensitivity of different techniques in the diagnosis of lung tumors
      with the flexible fiberoptic bronchoscope. Comparison of brush biopsy, imprint
      cytology of forceps biopsy, and histology of forceps biopsy.
AB  - Brush and forceps biopsies were done consecutively in 186 cases of pulmonary
      neoplasia with a flexible fiberoptic bronchoscope guided by x-ray television
      fluoroscopy. Imprint and histologic sections were prepared from all forceps
      biopsy specimens. The three techniques were compared for their diagnostic
      sensitivity. As a result 84.9% of all imprints, 80.6% of brush biopsy specimens,
      and 62.9% of histologic sections were positive for malignancy. The sensitivity of
      brush biopsy specimens was independent of the location and morphology of the
      tumors, but the sensitivity of forceps biopsy specimens was lower in neoplasms
      unidentified by bronchoscopy. The sensitivity of the diagnostic accuracy when all
      three methods were used jointly was 97.3%, and the specificity was 100%.
      Agreement in the final morphologic tumor type was found in 130 of 150 cases
      (86.7%) by positive brush biopsy specimens, in 136 of 158 cases (86.1%) by
      positive imprint cytology, and in 104 of 117 cases (88.9%) by positive histology
      from forceps biopsy specimens. For routine bronchoscopy, all three methods should
      be used in combination to obtain the highest diagnostic yield.

PMID- 1985727
TI  - The value of immunohistochemistry for collagen IV expression in colorectal
      carcinomas.
AB  - The Dukes' classification has well-established prognostic value in colorectal
      cancer patients. Yet, in each Dukes' class, the survival of individual patients
      may vary considerably. Recent studies show prognostic significance of genetic
      alterations in colorectal carcinoma. However, the importance of tumor stromal
      components noted in the surrounding tissue may have been overlooked by the
      methods used. Therefore, in a longitudinal study of 154 patients with colorectal
      cancer operated on between 1967 and 1974, the authors determined the influence on
      prognosis of lymphocytic infiltration and expression of collagen type IV in tumor
      stroma. Also, age, sex, Dukes' classification, grade of tumor differentiation,
      vasoinvasion, and the number of positive lymph nodes were analyzed. Follow-up was
      at least 15 years. Lymphocytic infiltration and collagen IV expression were
      scored as mild, moderate, or severe. Survival was analyzed by a Cox proportional
      hazards model. The density of lymphocytic invasion showed no significant
      influence on survival. Collagen IV expression analyzed as a single variable was
      significantly (P = 0.038) related to better prognosis in colorectal cancer
      patients. By multi-variate analysis collagen IV expression showed a trend toward
      better prognosis that was not statistically significant (P = 0.12). Dukes'
      classification (P less than 0.001), the presence of vasoinvasion (P = 0.009), and
      lymph node status (P = 0.04) significantly influenced survival. In conclusion
      immunohistochemistry for collagen IV is an important additional staining
      technique with prognostic value. In addition, collagen IV immunostaining
      facilitates recognition of vascular invasion by highlighting the basement
      membrane of vessels.

PMID- 1985728
TI  - Radiosurgery of acoustic neurinomas.
AB  - Eighty-five patients with acoustic neurinomas underwent stereotactic radiosurgery
      with the gamma unit at the University of Pittsburgh (Pittsburgh, PA) during its
      first 30 months of operation. Neuroimaging studies performed in 40 patients with
      more than 1 year follow-up showed that tumors were smaller in 22 (55%), unchanged
      in 17 (43%), and larger in one (2%). The 2-year actuarial rates for preservation
      of useful hearing and any hearing were 46% and 62%, respectively. Previously
      undetected neuropathies of the trigeminal (n = 12) and facial nerves (n = 14)
      occurred 1 week to 1 year after radiosurgery (median, 7 and 6 months,
      respectively), and improved at median intervals of 13 and 8 months, respectively,
      after onset. Hearing loss was significantly associated with increasing average
      tumor diameter (P = 0.04). No deterioration of any cranial nerve function has yet
      developed in seven patients with average tumor diameters less than 10 mm.
      Radiosurgery is an important treatment alternative for selected acoustic
      neurinoma patients.

PMID- 1985729
TI  - A phase II trial of carboplatin and vinblastine in the treatment of advanced
      squamous cell carcinoma of the esophagus.
AB  - Cisplatin-containing regimens are active in the treatment of esophageal cancer,
      with response rates of 25% to 35% in advanced disease. Carboplatin is less toxic
      than cisplatin; as a single agent, several responses were seen against esophageal
      tumors. To better define the role of carboplatin in esophageal cancer, the
      authors treated 19 chemotherapy-naive patients with advanced squamous cell
      carcinoma of the esophagus with carboplatin and vinblastine. Carboplatin (450
      mg/m2 intravenously [IV] on days 1, 29, 57, and every 6 weeks thereafter) was
      given with vinblastine (5 mg/m2 IV on day 1 and then every 2 weeks). No major
      responses were seen. No significant renal toxicity and only mild gastrointestinal
      toxicity (emesis, diarrhea) were observed. Hematologic toxicity was more severe
      in patients with prior radiation therapy (RT), with three of six patients with
      prior RT exhibiting Grade 4 hematologic toxicity. Although generally less toxic
      than cisplatin-containing regimens, carboplatin and vinblastine is also less
      active in the treatment of squamous cell carcinoma of the esophagus. Hematologic
      toxicity with this regimen was severe in patients who had received prior RT.

PMID- 1985730
TI  - Prolonged venous infusion of cisplatin and concurrent radiation therapy for lung
      carcinoma. A feasibility study.
AB  - Fifty patients with non resectable and/or inoperable bronchogenic carcinoma were
      entered into a feasibility study of cisplatin (CDDP) given in continuous infusion
      with concurrent radiation therapy. The radiation therapy regimen consisted of 2
      Gy given 5 days a week in the first 3 and last 2 weeks of a 7-week split course
      (50 Gy of total dose). The CDDP (daily dose of 4 to 6 mg/m2) was administered to
      cover the days of radiation treatment by means of a central venous catheter and a
      portable pump. Less than 1% of predicted duration of infusion was lost due to
      complications related to venous access and pump. Toxicity was moderate. The
      overall probability of a locoregional major response (complete + partial) within
      1 month after treatment completion was 86%. Twenty-three patients underwent
      resection. The 1-year actuarial probability of survival was 64%. The high
      response and survival rates warrant further studies on concurrent CDDP continuous
      infusion and radiation therapy in inoperable lung carcinoma.

PMID- 1985731
TI  - A phase II multi-institutional trial of low-dose N-(phosphonacetyl)-L-aspartate
      and high-dose 5-fluorouracil as a short-term infusion in the treatment of
      adenocarcinoma of the pancreas. A Southwest Oncology Group study.
AB  - Adenocarcinoma of the pancreas is a highly lethal malignancy and chemotherapy has
      had little impact on the natural history of this disease. PALA, used to
      potentiate 5-fluorouracil (5-FU), has been shown to have synergy in vivo and in
      vitro. Twenty-seven patients were treated with an intravenous push dose of PALA
      (250 mg/m2) followed 24 hours later with a 24-hour infusion of 5-FU (2600 mg/m2).
      This regimen was repeated weekly. There was one partial response of 21 eligible
      patients with an estimated response rate of 5%. Toxicity was severe with one
      toxic death and four patients experiencing Grade 4 toxicity. 5-Fluorouracil and
      PALA, given in the schedule described, do not appear to be effective against
      adenocarcinoma of the pancreas.

PMID- 1985732
TI  - A dose-intensive regimen of 5-fluorouracil for the treatment of metastatic
      colorectal carcinoma.
AB  - 5-Fluorouracil (5-FU) was delivered in a dose-intensive schedule to 23 patients
      with metastatic or unresectable colorectal carcinoma. The schedule consisted of
      bolus single-dose 5-FU therapy 400 to 500 mg followed by 4-day infusion of 5-FU,
      600 to 800 mg/m2/day, followed by a 17-day to 24-day infusion of 200 to 250
      mg/m2/day. Partial remissions were seen in 22% of all eligible patients.
      Significant toxicity, including mucositis, diarrhea, and hand-foot syndrome,
      necessitated dose reductions in most patients. The authors conclude that 5-FU
      given in this moderately intensive schedule is associated with a moderate level
      of response, as easily achieved with more conventional schedules or with 5-FU
      leucovorin combinations. Tumor responsiveness to dose intensive 5-FU regimens may
      be limited.

PMID- 1985733
TI  - Combined surgical resection and iridium 192 implantation for locally advanced and
      recurrent desmoid tumors.
AB  - Thirty-eight histologically confirmed desmoid tumors were treated with
      conservative surgical resection and interstitial iridium 192. Patients included
      in this series constituted a poor prognostic group. Seventy five percent (75%)
      had previous recurrences of their disease and 50% had tumors 8 cm or greater in
      size. In addition, 16% of the patients had gross residual disease after surgical
      excision and 79% had positive or close margins of resection. With a median follow
      up of 5.5 years, the 5-year actuarial in-field local control rate was 75% and the
      overall local control rate was 66%. Four of the 12 local recurrences developed at
      the periphery of the implant volume and four patients failed at least 3 cm or
      more beyond the treated volume. After salvage therapy, the 5-year actuarial local
      control rate was 95%. Two patients required amputation for recurrent disease.
      Thirty of 34 patients remain free of disease with an excellent functional result
      achieved. The authors conclude that surgical resection and postoperative
      interstitial iridium 192 is effective therapy for patients with desmoid tumors.
      Despite the fact that most patients in this series had bulky, recurrent tumors,
      excellent long-term local control and limb function were achieved.

PMID- 1985734
TI  - Second cancer after radiation therapy for cancer of the uterine cervix.
AB  - Radiation-induced cancers after radiation therapy for cancer of the uterine
      cervix were investigated on 11,855 patients including 5725 patients treated with
      radiation therapy alone, 1969 postoperative radiation therapy and 4161 surgery
      alone. The observed-to-expected ratios of the second primary cancer was 0.933 for
      the patients with radiation therapy alone and 1.074 for the patients with
      postoperative radiation therapy, respectively. No significant increase was
      observed in the risk of second primary cancers when all sites were combined.
      However, assessing on site by site basis, significant excess was noted for the
      rectum cancer, leukemia, and bladder cancer for the radiation therapy group but
      not for the surgery group. A significant excess of lung cancer was observed in
      both radiation therapy and surgery groups, which was attributed to some other
      causative factors. Radiation-induced cancers were suggested to develop apparently
      in organs involved in the irradiated field.

PMID- 1985735
TI  - Evaluation of a simple line width test involving magnetic resonance spectroscopy
      of plasma in carcinoma of the ovary.
AB  - Magnetic resonance spectroscopic (MRS) measurement of human plasma has been
      reported as a generally applicable marker for malignancy: patients with
      malignancy had a MRS line width significantly different from patients with benign
      diseases or healthy controls. The authors investigated the value of this test in
      213 women with ovarian carcinoma, benign pelvic masses, benign nongynecologic
      diseases, and healthy controls. The MRS measurements were performed on plasma
      samples at 21 degrees C or 27 degrees C. The line width parameters were obtained
      by averaging the width at half the height of the methyl and methylene peaks on
      the resonance spectra. At 27 degrees C using 33 Hz as the threshold for an
      abnormal result, there was a significant correlation between the result of the
      test and the presence or absence of malignancy. However, the study demonstrates
      that the specificity (0.44) and positive predictive value (0.42) are too low for
      the test to be useful in the management of patients with carcinoma of the ovary.
      At 21 degrees C no correlation between the results of the test and the clinical
      status of women with carcinoma of the ovary were observed. In 47 patients the
      test did not predict preoperatively the benign or malignant nature of a pelvic
      mass.

PMID- 1985736
TI  - A comparison of Ho's, International Union Against Cancer, and American Joint
      Committee stage classifications for nasopharyngeal carcinoma.
AB  - Five hundred sixty-four nasopharyngeal carcinomas (NPC), mostly of
      undifferentiated histologic type, were studied for survival, distant metastasis,
      and local recurrence. All had computerized tomography of the nasopharynx and
      skull base (CT-NP) and fiberoptic nasopharyngoscopy for evaluation of the primary
      tumor. Regional disease was assessed by palpation. A computer data base was
      formed on presentation, containing all information required for staging according
      to Ho's, the International Union Against Cancer (UICC), and the American Joint
      Committee (AJC) classifications. The three were compared for their efficacy in
      predicting prognosis. Ho's classification was superior to the other two because
      its overall stages differed from one another more significantly in the actuarial
      survival (ASR), disease-free survival (DFS), and freedom from distant metastasis
      (FDM) rates, and its N staging was more accurate in predicting FDM. Stages T1 and
      T2 of UICC/AJC were similar in the freedom from local recurrence rate (FLR) and
      should be grouped together, equivalent to Ho's T1. A more even patients number
      distribution among the stages also favored the use of Ho's classification.

PMID- 1985737
TI  - Non-Hodgkin's lymphoma of the brain after Hodgkin's disease. An
      immunohistochemical study.
AB  - Non-Hodgkin's lymphoma (NHL) of the central nervous system (CNS) is a rarely
      reported complication of Hodgkin's disease (HD). Two patients with NHL of the
      brain after HD were studied by histologic and immunohistochemical methods. Both
      patients were in the second decade, had been treated with radiation and
      chemotherapy, had experienced a relapse of HD before development of NHL, had no
      evidence of HD at the time of diagnosis of NHL, and died within 1 year of
      diagnosis. Both brain neoplasms were large cell immunoblastic lymphomas of B-cell
      lineage. Patients with HD appear to be at increased risk for NHL of the CNS,
      which may have a poor prognosis.

PMID- 1985738
TI  - DNA and RNA flow cytometric study in multiple myeloma. Clinical correlations.
AB  - Flow cytometric studies of cellular DNA and RNA content using the acridine-orange
      technique were conducted in 81 patients with multiple myeloma (MM). All patients
      were treated with the M-2 protocol and clinical response was evaluated according
      to the criteria of the Chronic Leukemia-Myeloma Task Force. Aneuploid DNA
      stemlines were found in 38.2% of untreated patients with a median DNA index (DNA
      I) of 1.15 in marrow aspirates and 1.22 in biopsy specimens. The median
      percentage of cells with abnormal DNA content was 31.5 (aspirates) and 35 (biopsy
      specimens) and a positive correlation with the percentage of bone marrow plasma
      cells was observed. Significantly higher proliferation (S-phase) was found in
      marrow biopsy specimens as compared with marrow aspirates. Significantly higher
      RNA content (RNA index [RNA-I]) was observed in aneuploid versus diploid patients
      in biopsy material. There was no difference in response to the Memorial Hospital
      M-2 protocol between diploid and aneuploid patients. In patients with DNA-I
      greater than 1.15 remission duration was shorter as compared with DNA-I less than
      or equal to 1.15. Furthermore, no difference in cellular RNA content was noted
      between responders and nonresponders. This study demonstrates no correlation
      between cellular RNA content and response, as previously described for patients
      treated with vincristine, Adriamycin, and dexamethasone (VAD), but DNA aneuploidy
      appears to be an adverse prognostic factor in MM patients treated with the M-2
      protocol. It also demonstrates that prognostic models for MM are not universal
      but depend on the chemotherapeutic regimen used.

PMID- 1985739
TI  - A comparative study of histopathology, hormone receptors, peanut lectin binding,
      Ki-67 immunostaining, and nucleolar organizer region-associated proteins in human
      breast cancer.
AB  - The current study was performed on 71 cases of human female breast cancer and
      compares the results of five morphologic methods developed for the detection of
      estrogen receptors (ER), progesterone receptors (PgR), lectin Peanut agglutinin
      (PNA) binding sites, monoclonal antibody Ki-67 immunoreactivity, and the mean
      number of argyrophilic nucleolar organizer regions (Ag-NOR). All the parameters
      were evaluated on serial cryostat sections representative of a closely related,
      if not identical, neoplastic population. A significant positive correlation was
      found between the occurrence of estrogen, progesterone, and peanut receptors and
      between Ki-67 immunoreactivity, mean number of NOR, and mitotic index.
      Furthermore, ER, PgR, and PNA receptors showed a significant, inverse correlation
      with Ki-67 immunoreactivity, mitotic index, and mean number of Ag-NOR. These
      results provide further data that support the hypothesis that (1) progesterone
      and PNA receptors are estrogen-induced and indicate a metabolic response of the
      target cells to functioning estrogen receptors; (2) the mean number of NOR
      reflects the cell kinetics of the tumor; and (3) metabolic differentiation of
      neoplastic cells is inversely correlated to the proliferation index.

PMID- 1985740
TI  - Nucleolar organizer regions in precancerous and cancerous lesions of the
      bronchus.
AB  - Using a silver staining technique, nucleolar organizer region-associated proteins
      (Ag-NOR) were studied in paraffin sections of five specimens of normal bronchial
      epithelium, eight of atypical squamous metaplasia, five of carcinoma in situ, and
      seven of microinvasive squamous cell carcinoma. The mean number of Ag-NOR in the
      nucleus were normal epithelium 1.2 +/- 0.1 (mean +/- SD), atypical squamous
      metaplasia (borderline lesion) 2.2 +/- 0.5, carcinoma in situ 3.8 +/- 0.6, and
      microinvasive squamous cell carcinoma 4.8 +/- 1.1. There was a highly significant
      difference between the Ag-NOR numbers in the atypical squamous metaplasia and
      those in the carcinoma in situ (P less than 0.01). The Ag-NOR staining is a
      useful technique for the differential diagnosis of difficult borderline lesions
      in the bronchial epithelium.

PMID- 1985741
TI  - Insulin secretion and action in patients with pancreatic cancer.
AB  - The authors investigated insulin secretory capacity and insulin action in 11
      preoperative patients with pancreatic carcinoma and 15 age-matched and weight
      matched healthy subjects (C). Five patients were classified as diabetic (D), two
      as impaired glucose tolerant (IGT), and four as nondiabetic (ND). Postabsorptive
      serum insulin levels (mean +/- SE, in uU/ml) in D (12 +/- 2), IGT (17 +/- 7), and
      ND (10 +/- 2) were comparable. After administration of 100 g of oral glucose,
      peak insulin achieved in D (60 +/- 11) was lower than in IGT (101 +/- 26) and ND
      (83 +/- 20), whereas peak insulin levels in IGT and ND were significantly (P less
      than 0.05) higher than in C (45 +/- 6). Comparable insulin response to nonglucose
      stimuli was documented in all subjects using the slow arginine infusion test with
      mean serum insulin of 27 +/- 4 in D, 28 +/- 6 in IGT, 34 +/- 10 in ND, and 32 +/-
      5 in C. In six patients (P) and six controls, insulin action was assessed by the
      euglycemic hyperinsulinemic clamp technique, with glucose turnover rates
      estimated by [3-3H]glucose infusion. Steady-state plasma glucose concentrations
      were maintained at 92 +/- 3 (P) and 91 +/- 1 mg/dl (C). After insulin infusion at
      the rate of 1.0 mU/kg/min, comparable high physiologic insulin levels were
      observed in P (73 to 104 uU/ml) and in C (81 to 103 uU/ml). Postabsorptive rates
      of endogenous glucose appearance (Ra) were higher in P (2.86 to 3.02 mg/kg/min)
      than in C (1.50 to 2.80 mg/kg/min). At high physiologic insulin concentrations,
      negative Ra values were documented in all subjects, and complete suppression of
      Ra was assumed. Total body glucose use (M) was consistently lower in P (3.90 to
      6.40 mg/kg/min) than in C (6.98 to 10.40 mg/kg/min), consistent with a state of
      insulin resistance. Patients with pancreatic cancer manifest insulin resistance
      by virtue of a decrease in total body glucose use (M) and decreased insulin
      response to glucose due to either inherent beta cell dysfunction or decreased
      islet cell mass. The latter is not identifiable by histologic morphology.

PMID- 1985742
TI  - Life-threatening airway obstruction at the presentation of Hodgkin's disease.
AB  - Mediastinal involvement from Hodgkin's disease is common. Significant symptoms
      resulting from disease at this site are less common and only rarely does severe
      airway obstruction occur. The authors report six cases of Hodgkin's disease in
      which life-threatening airway obstruction was a major feature of the clinical
      presentation and early clinical course. The literature describing this
      complication is reviewed. General anesthesia with endobronchial intubation should
      be avoided if at all possible in patients with airway obstruction and alternative
      methods of diagnosis and management are discussed.

PMID- 1985743
TI  - Long-term survival in Ki-1 lymphoma.
AB  - Three patients with histologic and immunologic features of Ki-1-positive large
      cell lymphoma, who experienced long-term survival, are presented. These three
      patients at 2, 28, and 49 years of age had adenopathy; all cases had been
      initially misdiagnosed as metastatic carcinoma or malignant histiocytosis. On
      subsequent review, they had sinusal and diffuse growth of large pleomorphic cells
      that were Ber-H2 (Ki-1; CD 30) positive. One case marked as a T-cell lymphoma
      with UCHL1, one case expressed T-cell and B-cell markers, and one case was
      negative for both T-cell and B-cell markers. All patients received chemotherapy,
      and two received local radiation. One patient was not treated until 9 years after
      initial diagnosis. Two patients had several recurrences, but there has been no
      evidence of lymphoma in any of the three patients for 63 to 301 months; overall
      survival time has ranged from 14 to 25 years. These cases are the longest
      reported survivors with Ki-1 lymphoma; 5 years was the longest survival time
      previously reported. It also is noteworthy that Ber-H2 and other lymphoid
      associated antigens appear to be preserved in formalin-fixed, paraffin-embedded
      tissues for prolonged periods. This may allow retrospective studies to evaluate
      the natural history of Ki-1 lymphomas, as well as their spontaneous or treatment
      induced regression.

PMID- 1985744
TI  - Obesity and body fat distribution and breast cancer prognosis.
AB  - This study addresses the effect of obesity and body fat distribution on axillary
      lymph node involvement, tumor size, and estrogen receptor (ER) level in breast
      cancer patients. Anthropometric measurements were prospectively obtained on 248
      consecutively and newly diagnosed women with invasive breast cancer. The
      anthropometric measurements evaluated were abdomen, thigh, subscapular, and
      midaxillary skinfolds; weight; and height. Weight and Quetelet Index (kg/m2) were
      significantly (P = 0.001) associated with lymph node involvement in
      postmenopausal patients. The abdomen:thigh skinfold ratio was significantly
      higher in premenopausal patients (P = 0.004) and postmenopausal (P = 0.03)
      without axillary node involvement compared with women with 4+ axillary node
      involvement. The abdomen:thigh skinfold was higher (P = 0.05) in women with
      smaller breast cancers (less than 2.0 cm) and higher ER levels. Weight and
      Quetelet Index did not affect tumor size or ER level. This study demonstrated
      that obese postmenopausal women who developed breast cancer tend to have more
      axillary node involvement than their leaner counterparts. Generalized obesity did
      not affect tumor size or ER level. Premenopausal and postmenopausal women with
      upper body fat distribution appear to be a subset of women who have a more
      favorable prognosis as measured by less lymph node involvement, smaller tumors,
      and higher levels of ER in their tumors.

PMID- 1985745
TI  - Prognostic implications of tumor diameter in carcinoma of the head of the
      pancreas.
AB  - Two hundred twenty patients with a carcinoma in the head of the pancreas were
      divided into three tumor diameter groups: group 1, 0.5 to 4.4 cm (n = 72); group
      2, 4.5 to 6.0 cm (n = 77); and group 3, 6.1 to 15.0 cm (n = 71). For these tumor
      diameter groups a six-fold eliminatory curability analysis was performed. Of the
      patients with liver metastases in group 1 the last patient had died at 10 months
      and in groups 2 and 3 no patients were alive at 18 months after the start of
      complaints. Patients with extrahepatic metastases did not survive 12 months in
      group 1, 16 months in group 2, and 25 months in group 3. The 6% actuarial
      survival rate for inoperable patients was reached in group 1 after 17 months, in
      group 2 after 36 months, and in group 3 after 27 months after the start of
      complaints. For groups 1 through 3 in curable, but not curatively operated
      patients, the respective 0% actuarial survival rate was reached at 24 months, 23
      months, and 14 months. The 0% actuarial survival rate in patients with
      irresectable vessel invasion was reached in group 1 at 33 months, in group 2 at
      23 months, and in group 3 at 25 months. The 0% actuarial survival rate in
      patients with an irresectable tumor was reached at 33 months, 31 months, and 27
      months after the start of complaints in groups 1, 2, and 3, respectively. The 0%
      actuarial survival rate in curatively operated patients was reached in group 3
      after 26 months and in group 2 after 29 months. In group 1 25% of the patients
      were alive at 36 months after the start of complaints. Small tumors were
      associated with the greatest chance of curative operation and on average had the
      longest survival. However, small tumors with liver or other metastases carried a
      worse prognosis than large tumors with liver or other metastases. If tumors were
      found not to be resectable at the time of operation, the size of the tumor did
      not appear to affect survival.

PMID- 1985746
TI  - Black tobacco, mate, and bladder cancer. A case-control study from Uruguay.
AB  - A case-control study of bladder cancer involving interviews with 111 incident
      cases and 222 controls was carried out in Montevideo, Uruguay. The analysis was
      conducted separately for each sex. Point estimates of relative risk associated
      with smoking variables, ingestion of infusions of the herb Ilex paraguariensis
      (mate), and selected dietary items were obtained by stratified and logistic
      regression analysis. Among men, smokers of black tobacco showed a relative risk
      (RR) 2.7 higher than blond tobacco smokers and mate exposure showed a significant
      dose-response, after adjustment for age, residence, social class, hospital, type
      of tobacco, smoking intensity, smoking duration, and vegetable consumption, with
      a seven-fold increase in risk for heavy consumers. Joint exposure to type of
      tobacco and mate consumption showed a multiplicative effect. Women showed a
      similar increase in risk with mate consumption. The results suggest that the high
      mortality rates of bladder cancer observed in Uruguay could be explained by the
      combined effect of black tobacco smoking and mate ingestion.

PMID- 1985747
TI  - Occult cancer in patients with deep venous thrombosis. A systematic approach.
AB  - The authors prospectively studied 113 consecutive patients with deep venous
      thrombosis of the lower extremities to determine the most appropriate workup
      study for searching for a hidden cancer. After a careful physical examination,
      the following routine tests were performed: erythrocyte sedimentation rate (ESR),
      whole blood counts, biochemistry, carcinoembryonic antigen (CEA) levels, chest
      radiograph, upper gastrointestinal endoscopy, abdominal ultrasound and computed
      tomography (CT) scan. If a malignant lesion was suspected, further appropriate
      studies were performed. After discharge, periodic follow-up was performed on all
      patients in the outpatient clinic. A malignant neoplasm was detected in 12
      patients. Of these 12 patients, six were asymptomatic with the exception of
      experiencing thrombophlebitis. Cancer was found more commonly in patients with
      idiopathic deep vein thrombosis (DVT) (7 of 31 versus 5 of 82 patients with
      secondary DVT; P = 0.012), and in those patients with abnormal lactic
      dehydrogenase (LDH) levels (6 of 23 versus 6 of 90; P = 0.007). Abnormal CEA
      levels allowed diagnosis of two cases of colonic cancer (on colonoscopy). Both
      ultrasound and CT scan of the abdomen showed two cases of urinary bladder
      carcinoma at a very early stage. Furthermore, two cases of adenomatous polyps in
      colon were found, a condition considered by most authors to be a colorectal
      cancer precursor. In addition, there were five patients with large benign pelvic
      tumors, and two patients with absent inferior vena cava. The most striking
      finding was that some cases of cancer were at a very early stage. It was
      concluded that blood cell counts, LDH, CEA, chest radiograph, and abdominal
      ultrasonography (or CT scan) should be routinely performed on all patients with
      deep venous thrombosis (particularly those with idiopathic DVT). Malignancy would
      not have been recognized in some patients if these tests had not been performed.

PMID- 1985748
TI  - A pilot study of intermediate-dose methotrexate and cytosine arabinoside, "spread
      out" or "up-front," in continuation therapy for childhood non-T, non-B acute
      lymphoblastic leukemia. A Pediatric Oncology Group study.
AB  - One hundred six children with newly diagnosed non-T-, non-B-cell acute
      lymphoblastic leukemia (ALL) were treated in a Pediatric Oncology Group (POG)
      pilot study in which six courses of intermediate-dose methotrexate (MTX) and
      cytosine arabinoside (Ara-C) (1 g/m2 each) were added to a "backbone" of standard
      continuation therapy. The dose and sequence of MTX/Ara-C administration were
      based on a preclinical model that demonstrated synergism between MTX and Ara-C.
      Poor-risk patients (n = 49) were assigned to "up-front" therapy, in which the
      MTX/Ara-C courses were administered during the initial 15 weeks of remission.
      Standard-risk patients (n = 57) were assigned to "spread-out" therapy, in which
      the MTX/Ara-C courses were interspersed at 12-week intervals within continuation
      treatment. Toxicity after intermediate-dose MTX/Ara-C, principally neutropenia
      and fever, was judged significant but manageable. Unexpectedly, the incidence of
      fever and neutropenia less than 500/mm3 was greater after "spread-out" therapy
      (38%) than after "up-front" therapy (6%). At 4 years, the Kaplan-Meier estimate
      of event-free survival (EFS) is 71% (+/- 7%) for standard-risk patients and 53%
      (+/- 8%) for poor-risk patients. The results of this pilot study support the use
      of intermediate-dose MTX/Ara-C in additional studies.

PMID- 1985749
TI  - Multidisciplinary treatment of primary orbital rhabdomyosarcoma. A single
      institution experience.
AB  - Orbital rhabdomyosarcoma accounts for one-fourth of the primary tumors in the
      head and neck region. Modern treatment modalities have led to a 2-year survival
      rate of about 90% in these patients. However, new therapeutic trials are designed
      to reduce complications and salvage more than 90% of orbital cases. Between 1979
      and 1990, 12 children affected by primary orbital rhabdomyosarcoma have been
      diagnosed and treated at the University of Naples. Ten of them have been
      uniformly treated by biopsy, followed by immediate radiation and combined
      chemotherapy. All 12 patients are alive and free of detectable disease, from a
      minimum of 7 months to a maximum of 123 months after diagnosis. In all children,
      ocular structures have been spared and the complications observed until now have
      been few. The above results suggest that the association of immediate radiation
      therapy and chemotherapy might represent an optimal tool for treatment of orbital
      rhabdomyosarcoma.

PMID- 1985750
TI  - Combination therapy for anaplastic giant cell thyroid carcinoma.
AB  - Since 1981, 20 patients with anaplastic giant cell carcinoma of the thyroid have
      been prospectively treated according to a combination regimen of chemotherapy and
      external beam radiation therapy. Two types of chemotherapy were used every 4
      weeks, depending on the patient's age. For those younger than 65 years, a
      combination of doxorubicin (60 mg/m2) and cisplatin (90 mg/m2) was given, and for
      older patients mitoxantrone (14 mg/m2) was used. Radiotherapy was carried out
      between Day 10 and Day 20 of the first four cycles of chemotherapy. It delivered
      17.5 Gy in 7 fractions to the neck and the superior mediastinum. Survival
      exceeding 20 months was observed in three patients. Complete neck tumor response
      was observed in five patients, among whom four had undergone previous operations.
      No response was seen in distant metastases, which were the cause of death in 14
      patients. These treatment modalities are effective in some patients, both in
      terms of survival and of local control, avoiding death from local invasion. Gross
      tumor resection should be performed whenever possible but should not delay the
      commencement of this protocol. Toxicity was high and remains the main limiting
      factor.

PMID- 1985751
TI  - Primary treatment of large and massive adult sarcomas with iododeoxyuridine and
      aggressive hyperfractionated irradiation.
AB  - For a decade, the authors have experimented with treatment for unresectable adult
      soft tissue and bony sarcomas. Over the last 6 years, they have combined
      hyperfractionated radiation therapy and intravenous iododeoxyuridine as a
      radiosensitizer, in regimens designed to minimize toxicity and permit delivery of
      aggressive radiation therapy. Patients with solitary lesions and those with
      metastasis (38%) were treated in the hope of both potential cure in some and
      durable palliation in others. The most formidable of these cancers have been
      those that are large or massive, often requiring five or more fields and
      extensive treatment planning. The authors report results from 36 patients with
      large unresectable sarcomas (tumors ranging from 5 to 35 cm; average 14 cm)
      treated with hyperfractionated radiation therapy, with a minimum follow-up of 1
      year, follow-up of 4 or more years (in 50%), or follow-up until death. Overall
      local control has been 60%, with control of 66% of lesions from 5 to 9 cm, 63% of
      those from 10 to 14 cm, 63% of those from 15 to 19 cm, and 57% of those greater
      than 20 to 40 cm. Morbidity has been modest. This experience compares favorably
      with the authors' earlier trials with misonidazole, and toxicity has been reduced
      considerably.

PMID- 1985752
TI  - Ultrasound and ultrasound-guided fine needle aspiration biopsy of supraclavicular
      lymph nodes in patients with esophageal carcinoma.
AB  - The use of ultrasound combined with ultrasound-guided fine-needle aspiration
      biopsy (UGFAB) of supraclavicular lymph nodes in the pretreatment staging of 37
      patients with squamous cell carcinoma of the esophagus is described. All patients
      underwent computed tomography (CT) scans of the chest and the abdomen and
      ultrasound of the abdomen and supraclavicular regions. Supraclavicular lymph node
      metastases (Stage IV disease according to the tumor nodes metastasis [TNM]
      classification) were cytologically diagnosed in seven (18.9%) of the 37 patients.
      In two of these patients, no other metastases were found. In the other five
      patients, UGFAB replaced more invasive diagnostic procedures. Due to their
      superficial location, ultrasound and UGFAB of the supraclavicular lymph nodes was
      relatively simple to perform, and contributed to an improved staging of squamous
      cell carcinoma of the esophagus.

PMID- 1985753
TI  - Altered protein tyrosine kinase levels in human colon carcinoma.
AB  - To further understand the molecular mechanisms and the biological indicators of
      colonic tumorigenesis, the authors examined tyrosine kinase activity in the
      cytosol and in the particulate fraction of the homogenates of specimens from 20
      human colonic carcinomas and compared them with the adjacent normal mucosal
      tissues. Total protein tyrosine kinase activity could be precisely detected using
      miniphosphocellulose column purification and a synthetic peptide, Glu-asparagine
      (Asp)-alanine (Ala)-Glu-tyrosine (Tyr)-Ala-Ala-arginine (Arg)-Arg-Arg-glycine
      (Gly) (E11-G1), as an artificial substrate. Tyrosine kinase activity of colonic
      carcinoma and normal mucosa was reduced in the cytosol fraction whereas activity
      in the particulate fraction was elevated with respect to protein concentration.
      The average specific activity ratios were 1.95 +/- 0.27 (normal
      cytosolic/carcinoma cytosolic) and 0.57 +/- 0.01 (normal particulate/carcinoma
      particulate) for tyrosine kinase activity. Cellular distribution (% cytosol) of
      tyrosine kinase activity in normal mucosa and in carcinoma varied from 21.0% to
      91.2% and from 7.0% to 61.4%, respectively. In nearly all cases the percentage of
      cytosolic tyrosine kinase activity in carcinoma tissues was lower than in normal
      tissues. There was no difference due to histologic type or the presence of
      adenomatous components. A significant decrease of cytosolic tyrosine kinases was
      correlated with Dukes' Stage A. With advancing Dukes' stage, the average specific
      activity ratios (normal cytosol/carcinoma cytosol) were decreased. This study
      indicates that colonic carcinogenesis might be associated with alterations in
      cellular levels of tyrosine kinase activity and that the average specific
      activity ratio (normal cytosol/carcinoma cytosol) had a possible correlation with
      colonic tumor growth.

PMID- 1985754
TI  - Watch and wait after careful surgical treatment and staging in well
      differentiated early ovarian cancer.
AB  - Patients with well-differentiated epithelial ovarian cancer Stages Ia, Ib, Ic,
      and IIa (FIGO 1976) were observed after surgical treatment without adjuvant
      therapy. Careful surgical staging was required, and the extent of the staging
      procedure was assessed in each individual patient. There were 107 patients
      entered in the study by nine Dutch oncology centers. Of these 107, 21 did not
      fulfill all of the inlet criteria of the study and were excluded. Central
      pathologic review was performed in the remaining 86 cases, revealing that there
      was borderline tumor in seven patients, moderately or poorly differentiated tumor
      in nine patients, and tumor of nonepithelial histologic cell type in one patient.
      In two cases, no material for histologic review was available. After exclusion of
      these 19 cases, 67 patients were further analyzed. None of these 67 patients was
      lost during the follow-up period that ranged from 19 to 99 months (mean, 50
      months). Tumor recurrence was found in four patients after 11, 25, 34, and 34
      months of follow-up, all of whom died shortly after diagnosis of the recurrence
      without satisfactory response to secondary treatment. For the patients who
      underwent the most extensive staging procedure, disease-free 5-year survival was
      100%. For the patients who were inaccurately staged, disease-free 5-year survival
      was 88%. It was concluded that well-differentiated early stage (Ia-IIa) ovarian
      cancer carries an excellent prognosis after surgical treatment and complete
      surgical staging, with the possible exception of patients with Stage Ic disease
      with malignant peritoneal washings. Furthermore, it was considered that the
      application of more objective and consistent ways of assessing tumor grade should
      be encouraged. Surgical staging should be regarded as the golden standard in
      defining subsets of low-risk patients and should be included and clearly defined
      in future trials on early ovarian cancer.

PMID- 1985755
TI  - Clinical characteristics of high-grade lymphomas with immune genes in germline
      configuration.
AB  - In a prospective study of 42 high-grade lymphomas which were categorized
      according to the Kiel classification, the clinical significance of immune
      genotyping was studied. Immunoglobulin (Ig) and T-cell receptor (TCR) gene
      rearrangements were investigated. In 33 cases the immune genotype confirmed the
      phenotype. In one case with equivocal phenotype a TCR beta-chain rearrangement
      proved the T-cell origin of the lymphoma. None of the cases showed a bigenotype.
      There were eight lymphomas with immunoglobulin and TCR beta-chain and gamma-chain
      genes in germline configuration, which were divided into a group of immature
      lymphomas and a group of lymphomas with a more mature phenotype. The immature
      lymphomas had widespread disease, rapid progression, and favorable prognosis
      after intensive chemotherapy. The group of T-cell and Ki-1 lymphomas with null
      cell genotype was clinically heterogeneous. Three of four cases were secondary
      lymphomas after lymphomatoid papulosis, lymphomatoid granulomatosis, or Hodgkin's
      disease. All cases presented with extranodal involvement. Only one of these
      patients is in continuous remission. In conclusion, the lack of immunoglobulin
      and TCR beta-chain and gamma-chain gene rearrangements does not exclude the
      diagnosis of high-grade malignant lymphoma, especially in cases with unusual
      extranodal involvement. However, the DNA analysis identifies a null-cell genotype
      subset of high-grade lymphomas which may have clinical significance.

PMID- 1985756
TI  - Immunosuppressive acidic protein in malignant diseases. Clinical relevance?
AB  - The immunosuppressive acidic protein (IAP) has been described as a tumor
      associated marker in some solid tumors and hematologic diseases. To define the
      clinical relevance the authors determined the serum IAP levels in 194 patients
      with malignancies before initiation of therapy, 14 patients with idiopathic
      thrombocytopenic purpura (ITP), 28 patients with bacterial pneumonia, and 23
      healthy volunteers. Immunosuppressive acidic protein was measured by radial
      immunodiffusion. The mean value of our controls was 405 +/- 48 micrograms/ml.
      This is consistent with published data. The mean values for patients with
      malignancies varied from 554 micrograms/ml to 698 micrograms/ml. These are only
      marginally higher than those observed for the controls. In contrast patients with
      bacterial pneumonia demonstrated significantly elevated values (1038 +/- 261
      micrograms/ml). The authors conclude that IAP cannot be used as a diagnostic
      marker for the malignant diseases examined in this study.

PMID- 1985757
TI  - Loss of expression of blood group antigen H is associated with cellular invasion
      and spread of oral squamous cell carcinomas.
AB  - Membrane-bound carbohydrates may influence the metastatic behavior of cancer
      cells. Forty-two squamous cell carcinomas (SCC) of the buccal and maxillary
      alveolar mucosa were studied retrospectively using a monoclonal antibody (BE2)
      that reacts with blood group H (type 2 chain) structure. H-antigen staining
      within the entire tumor did not correlate with the stage of the tumor, i.e.,
      spread of the tumors. However, loss of staining within the most invasive sites of
      the tumors correlated significantly with the stage of tumor development and
      histologic grade of malignancy. These findings support the view that features
      relating to the cells of deeper parts of the carcinomas are very important for
      the clinical behavior of the tumors, and that loss of H-antigen expression is
      related to the stage of tumor and invasion of carcinoma cells.

PMID- 1985758
TI  - Osteosarcoma in young children.
AB  - The clinicopathologic features of osteosarcoma in 12 children younger than 16
      years of age treated at The Children's Hospital and Dana-Farber Cancer Institute,
      Boston, during a 70-year time period are presented. Only one of six children
      treated before 1972 is a long-term survivor. Four of six children (67%) treated
      after 1972 are disease-free with an average follow-up of 8.8 years. The year 1972
      marked the onset of use of effective chemotherapy in osteosarcoma, namely, high
      dose methotrexate and leucovorin rescue. It would appear that the pathologic
      features and behavior of osteosarcoma in young children is similar to that of
      osteosarcoma in older children and adolescents. A combination of complete (wide)
      surgical resection or amputation and aggressive chemotherapy offers the best
      chance of long-term survival.

PMID- 1985759
TI  - Clinicopathologic characteristics of adenosquamous carcinoma of the lung.
AB  - Fifty-six cases of surgically resected adenosquamous carcinoma of the lung were
      studied clinicopathologically, and their outcome was compared with that of
      adenocarcinomas and squamous cell carcinomas of the lung. The frequency rate of
      adenosquamous carcinoma was 2.6% of 2160 primary lung cancers resected in the
      National Cancer Center Hospital (Tokyo, Japan). The survival curves of patients
      with adenosquamous carcinomas, adenocarcinomas, and squamous cell carcinomas
      indicated that the outcome of adenosquamous carcinoma was poorer than that of
      adenocarcinomas and squamous cell carcinomas, particularly in Stages I and II.
      The amount of adenocarcinoma component did not affect the survival rate, although
      the histologic features of metastatic lymph nodes was somewhat influenced by the
      histologic type of the primary tumors. The histologic subtype of adenosquamous
      carcinoma was one of the independent prognostic determinants.

PMID- 1985760
TI  - Myeloma of the head of the pancreas. A case report.
AB  - A 45-year-old man was diagnosed with multiple myeloma, IgA-kappa, in 1975.
      Thirteen years later he presented with obstructive jaundice. Computed tomography
      (CT) showed a 6-cm mass in the head of the pancreas. Needle aspiration showed
      myeloma. The jaundice resolved after treatment with radiotherapy. Extraosseous
      involvement by myeloma is frequently found at autopsy but obstructive jaundice
      from myeloma of the head of the pancreas is quite rare. This atypical
      complication of myeloma may be related to the patient's long survival.

PMID- 1985761
TI  - Acute respiratory failure and pulmonary thrombosis in leukemic children.
AB  - Acute respiratory failure (ARF) in an 11-year-old child with pre-T acute
      lymphoblastic leukemia (ALL) at the beginning of induction therapy was observed,
      connected with a pulmonary thrombosis and not with an infective origin. A
      systematic search for this pathology identified six other children with the same
      pulmonary complication, five of whom where in the early phase of acute
      nonlymphoblastic leukemia (ANLL) and one in induction therapy for ALL in marrow
      relapse. At the beginning of the symptomatology, all children presented severe
      hypoxia and hypercapnia, with no or minimal chest radiograph abnormalities and no
      clear hemodynamic involvement. In all patients the arteriography and nuclear
      imaging studies confirmed the diagnosis. The causes of the thrombi could be
      connected with neoplastic emboli after cell lysis and/or with the vascular damage
      resulting from antiblastic therapy. Intravenous urokinase treatment and
      respiratory assistance had been successfully carried out in six of seven
      children.

PMID- 1985762
TI  - Pregnancy outcome in hematologic malignancies.
AB  - By means of a mail questionnaire, information on a series of 56 pregnancies i in
      48 women diagnosed with leukemia or lymphoma was collected from ten hospitals.
      Seven patients conceived while receiving treatment for their neoplasms; in 22
      patients, the hematologic disease was diagnosed during pregnancy, and the
      remaining 27 patients became pregnant after completion of the antineoplastic
      treatment. When a comparison was made of the evolution of these pregnancies to
      that of pregnancies in a healthy population, no increase in the incidence of
      complications was observed: 64% of the pregnancies went to term, 9% resulted in
      spontaneous abortion, and 5% resulted in premature births. The observed incidence
      of one major malformation in 56 pregnancies did not differ from the frequency of
      malformations in the offspring of healthy individuals. There were no fetal losses
      in six pregnancies in which conception occurred during the first year after
      chemotherapy. In spite of the inherent limitations derived from the design of
      this type of study and the type of subject analyzed, the data here support the
      hypothesis that the cytostatic treatment of hematologic malignancies, if deemed
      necessary, should not be postponed because of pregnancy. Moreover, the authors
      agree with advice recommending that no antifolic or alkylating agents be used for
      prolonged periods and that radiotherapy be avoided, especially to those fields
      involving the pelvic area.

PMID- 1985763
TI  - Clinical presentation, treatment, and outcome of trilateral retinoblastoma.
AB  - In this report, three new cases of trilateral retinoblastoma are presented. The
      clinical presentation, treatment, and outcome of the patients are described and
      compared with those of 32 cases that have been previously reported in the
      literature. A positive family history was obtained in 68% of the patients. The
      mean age at diagnosis of bilateral retinoblastoma was 7.2 months. The mean age at
      diagnosis of trilateral disease was 39.7 months, resulting in a mean latent
      interval of 32.6 months. The mean time from diagnosis of trilateral
      retinoblastoma to death was 6.6 months, and all patients died with spinal
      metastases. The patients who received no therapy survived an average of 1.3
      months after the diagnosis of trilateral disease. The patients who received any
      form of definitive therapy survived 9.7 months. Five patients who had complete or
      dramatic response to therapy by computed tomography scans had local intracranial
      tumor present at autopsy. Therefore, more aggressive local therapy may be
      warranted.

PMID- 1985764
TI  - The role of infection in the morbidity and mortality of patients with head and
      neck cancer undergoing multimodality therapy.
AB  - Cancer of the head and neck is a common cancer worldwide. The majority of
      patients present with locally advanced disease. Recently a great deal of
      improvement has been made in multimodality therapy of this disease, warranting
      more careful consideration of factors affecting quality of life, disease course,
      and treatment. Infection is clearly a factor. Analysis of 662 hospital admissions
      of 169 head and neck cancer patients was performed. A definite infection was
      documented in 86 febrile episodes, pneumonia contributed to 40%, bacteremia to
      13%, skin and soft tissue infection to 12%, and tracheobronchitis to 10%. Among
      the evaluated risk factors, foreign bodies, specifically intravenous (IV)
      cannulae and gastrostomy tubes, race, performance status, alcohol intake, and
      nutritional status were statistically significant variables that predicted for or
      were associated with infection. Infection contributed to 44% of the deaths.

PMID- 1985765
TI  - Factors related to and consequences of weight loss in patients with stomach
      cancer. The Norwegian Multicenter experience. Norwegian Stomach Cancer Trial.
AB  - Of 1165 patients with stomach cancer included in a national, prospective
      multicenter study with 51 surgical units participating, information about weight
      loss before diagnosis was available for 855 patients (73%). Median weight loss
      was 5 kg; 259 patients (31%) experienced no weight loss. By logistic regression
      analysis the authors found that weight loss increased with age and advancing
      stages of disease (TNM Stage I-IV), with decreasing Karnofsky index, in Lauren's
      diffuse versus intestinal tumor type, and with tumors located at the
      cardia/esophagus. Increasing weight loss reduced the resectability rate
      significantly, but no association between weight loss and postoperative
      complication rate was found. The odds ratio for postoperative mortality was 2.5
      to 1 for the weight loss group 5 to 10kg versus 0 kg. In conclusion, weight loss
      reflects a less favorable tumor status. Weight loss did not increase
      postoperative morbidity but did lead Weight to a higher death rate after surgery.

PMID- 1985766
TI  - Intrapericardial infusion of 5-fluorouracil. An unusual complication of a Hickman
      catheter.
AB  - Venous access devices (VAD) have become an important tool in the management of
      patients with cancer. Multiple complications can occur as a consequence of
      insertion of a VAD. The authors report a case of a Hickman catheter perforating
      the wall of the superior vena cava into the pericardium, resulting in accidental
      intrapericardial infusion of 5-fluorouracil (5-FU). Pericarditis and cardiac
      arrhythmias developed, but the patient did not have cardiac tamponade. She
      recovered from the event without apparent chronic cardiac dysfunction.

PMID- 1985767
TI  - Zinc and copper in breast cancer. A joint study in northern Italy and southern
      France.
AB  - The relationship between breast cancer and two trace elements, zinc (Zn) and
      copper (Cu), was investigated by means of an hospital based case-control study at
      Milan (Italy) and Montpellier (France). Variables concerning dietary intake of Zn
      and Cu (in Milan) and their blood levels (both in Milan and Montpellier) were
      measured. Dietary intake, evaluated through a questionnaire of the dietary
      history type, and blood levels of Zn and Cu were measured in 261 cases and 261
      controls. Cu blood level showed a contradictory tendency in the two samples
      (higher in controls in Milan, higher in cases in Montpellier), which tended to
      lessen after adjustment for related variables. No odds ratios (OR) in the
      different quantiles, nor X2 for trend reached statistical significance. A sharp
      difference was evidenced on the opposite with regard to Zn blood values in cases
      and controls. In both samples Zn mean values are significantly higher in cases
      than in controls, and the difference remains significant in the two samples even
      after adjustment for related variables. The pooled OR computed from the two
      samples, after adjustment for known risk factors and related variables, reaches
      in the fourth quartile a value of 9.5 (CI: 4.9-18.2). Dietary intake of the two
      minerals (measured only in Milan sample) showed no difference between cases and
      controls, but a stronger relationship between dietary and blood Zn was evidenced
      in cases with respect to controls. The authors suggest that the higher Zn level
      in cases might be related with an higher incorporation of Zn in cancer cases and
      that the same mineral might play a possible role in tumor growth promotion.

PMID- 1985769
TI  - Release of 7-alkylguanines from N-(2-chloroethyl)-N'-cyclohexyl-N-nitrosourea
      modified DNA by 3-methyladenine DNA glycosylase II.
AB  - Purified bacterial 3-methyladenine DNA glycosylase II releases four 7
      alkylguanines from [3H]N-(2-chloroethyl)-N'-cyclohexyl-N-nitrosourea-modified
      DNA: 7-(2-hydroxyethyl)guanine,1,2-bis(7-guanyl)ethane, 7-(2-chloroethyl)guanine,
      and 7-(2-ethoxyethyl)guanine. 7-(2-Ethoxyethyl)guanine, a new compound, is formed
      as a result of an interaction with ethanol, a common solvent for the 2
      haloethylnitrosoureas. Of the four 7-alkylguanines which are released from [3H]N
      (2-chloroethyl)-N'-cyclohexyl-N-nitrosourea-modified DNA, 7-(2
      hydroxyethyl)guanine is released at a rate very much slower than the other three.
      As shown by a study of the spontaneous decomposition of the corresponding 7-alkyl
      deoxyguanines, differences in chemical stability do not appear to explain the
      slow release of 7-(2-hydroxyethyl)guanine. In view of previous results showing a
      difference in the distribution of alkylation products between sensitive and
      resistant glial cell lines, the broad specificity of this enzyme suggests that
      glycosylase activity could play a role in cellular resistance to 2
      haloethylnitrosoureas.

PMID- 1985768
TI  - Comparative epidemiology of cancer between the United States and Japan. A second
      look.
AB  - Vital statistics were examined for the years 1955 through 1985 for Japanese
      natives and United States whites to elucidate changes in cancer mortality and
      related antecedent patterns of life-style in these two populations. Results show
      that lung cancer rates are rapidly accelerating among Japanese males as a
      consequence of their prior history of heavy cigarette smoking. Oropharyngeal
      cancer rates are also rising in Japan paralleling increases in alcohol and
      tobacco utilization. As the Japanese life-style and diet continue to become more
      "westernized," the rates of malignancies of the breast, ovary, corpus uteri,
      prostate, pancreas, and colon also continue to rise. Nevertheless, the mortality
      patterns of certain malignancies, viz., laryngeal, esophageal, and urinary
      bladder cancer, are discrepant with their established risk factor associations,
      suggesting the existence of other differences in risk factor exposure between the
      two countries. Epidemiologists and health educators need to develop innovative
      international programs of investigation and health promotion with preventive
      impact on common malignancies associated with risk factors of life-style.

PMID- 1985770
TI  - A phase I clinical trial of novobiocin, a modulator of alkylating agent
      cytotoxicity.
AB  - Antineoplastic drug resistance is a major obstacle to improved treatment of most
      adult cancers in humans. Novobiocin, an antibacterial agent which inhibits the
      eukaryotic topoisomerase II enzyme, increases the cytotoxicity of several
      alkylating agents in vitro by the formation of lethal DNA-DNA interstrand cross
      links, perhaps by decreasing the repair of drug monoadducts. In murine tumors
      treated in vivo novobiocin markedly potentiates alkylating agent cytotoxicity
      without concomitant increases in host toxicity. With this background, a Phase I
      trial of novobiocin and cyclophosphamide was performed in refractory cancer
      patients. Novobiocin was given p.o. for 96 h; 750 mg/m2 of i.v. cyclophosphamide
      was administered at 48 h. Thirty-four patients received 65 courses. The dose
      limiting toxicity of novobiocin in this trial was vomiting. The maximum tolerated
      dose was 6 g/day. Six of 34 patients had Grade III or IV mylosuppression but no
      dose escalation effect was noted. Three patients developed allergic reactions
      which resolved completely. No other significant toxicity occurred. While no dose
      dependent effect on serum novobiocin levels occurred, 18 of 19 patients treated
      at greater than or equal to 4 g daily had serum levels greater than or equal to
      100 micrograms/ml at steady state, a level which corresponds to levels used in
      vitro and seen in vivo where the murine novobiocin half-life of 82 min is far
      less than that seen in humans (6.0 h). Two of 30 evaluable patients had partial
      responses. Four other patients had stable disease. Four of six had prior disease
      progression on cyclophosphamide combination therapy. Novobiocin is well tolerated
      in patients receiving cyclophosphamide and blood levels are in the drug
      potentiating range. Phase II trials in cyclophosphamide refractory patients are
      anticipated.

PMID- 1985771
TI  - Cytotoxic activity of an anti-transferrin receptor immunotoxin on normal and
      leukemic human hematopoietic progenitors.
AB  - The process of cellular iron uptake involves a specific receptor for the plasma
      carrier transferrin and a pathway of receptor-mediated endocytosis. Transferrin
      receptor expression is closely related to the rate of cell proliferation, and
      conjugates between anti-transferrin receptor monoclonal antibodies and toxins
      have been shown to have potent cytotoxic activity. We have constructed an anti
      transferrin receptor immunotoxin by conjugating the anti-transferrin receptor
      monoclonal antibody B3/25 to a ribosome-inactivating protein, the saporin-6
      (SO6), which is derived from the seeds of the plant Saponaria officinalis. The
      immunotoxin B3/25-SO6 was tested for in vitro cytotoxic activity against the
      human cell lines K-562 and HL-60 and against normal human bone marrow
      hematopoietic progenitors and acute myeloid leukemia clonogenic cells. The
      immunotoxin proved to be an effective inhibitor of K-562 and HL-60 clonogenic
      cell growth, in vitro colony formation being completely inhibited at immunotoxin
      concentrations ranging from 10(-7) to 10(-10) M. B3/25-SO6 markedly reduced the
      recloning efficiency of HL-60 clonogenic cells at 10(-12) M. Exposure of HL-60
      cells in suspension culture to 10(-9) M B3/25-SO6 for 48-72 h completely
      abolished their clonogenic potential. The immunotoxin was also found to be
      cytotoxic against normal human bone marrow progenitor cells (burst-forming unit
      erythroid and colony-forming unit-granulocyte, macrophage) in a dose-dependent
      manner. However, exposure of normal colony-forming unit-granulocyte, macrophage
      in suspension culture to 10(-9) M B3/25-SO6 for 72 h resulted in only 50%
      suppression of their clonogenic potential. Finally, B3/25-SO6 was found to be a
      potent inhibitor of in vitro growth of acute myeloid leukemia clonogenic cells.
      The cytotoxic effects of B3/25-SO6 were shown to be specific, since both saporin
      alone and irrelevant immunotoxins did not have any effect in the cellular systems
      examined. We conclude that the immunotoxin B3/25-SO6 has dose-related cytotoxic
      effects on both normal and leukemic human hematopoietic progenitors. Since there
      are substantial differences between normal and leukemic progenitors with respect
      to the proportion of cycling cells and the expression of transferrin receptors,
      B3/25-SO6 or similar immunotoxins may have clinical application in bone marrow
      purging procedures.

PMID- 1985772
TI  - Cooxidation of cyclophosphamide as an alternative pathway for its bioactivation
      and lung toxicity.
AB  - A single i.p. dose of cyclophosphamide produces lung cell injury and fibrosis in
      mice. Although cyclophosphamide is activated by the cytochrome P-450 mixed
      function oxidase (MFO) system, a role for this system in the development of lung
      injury has not been established. The involvement of other metabolic pathways,
      such as cooxidation via prostaglandin H synthase, in the toxicity of
      cyclophosphamide has not been studied. The objectives of the current study were
      to assess the effects of various inhibitors of MFO and prostaglandin H synthase
      activity on the development of cyclophosphamide-induced lung damage and fibrosis
      in mice, to determine whether arachidonic acid as well as NADPH could support the
      activation of cyclophosphamide to an alkylating metabolite, and to assess the
      capacity of cyclophosphamide to serve as a reducing cosubstrate. In addition, the
      ability of a low dose of cyclophosphamide to prevent the lung injury from a later
      higher dose was determined. Treatment with SKF 525A, piperonyl butoxide, or 1
      benzylimidazole, followed by a single 200 mg/kg dose of cyclophosphamide, did not
      diminish pulmonary thymidine incorporation (an index of cell division after
      injury) or hydroxyproline content (an indicator of fibrosis), compared to mice
      treated with cyclophosphamide alone. Pretreatment with 1-aminobenzotriazole
      reduced the incorporation of thymidine into lung DNA on days 3 and 10, but not on
      day 7, and also reduced lung hydroxyproline accumulation. Treatment with
      indomethacin, nordihydroguiaretic acid, or aspirin prior to cyclophosphamide
      greatly reduced levels of pulmonary thymidine incorporation and/or hydroxyproline
      content, compared to cyclophosphamide alone. Low dose pretreatment with
      cyclophosphamide did not prevent the lung injury or fibrosis from a subsequent
      higher dose. NADPH supported greater production of alkylating metabolites in
      liver than in lung microsomes. In contrast, the arachidonic acid-supported
      production of alkylating metabolites was greater in lung microsomes. No NADPH- or
      arachidonate-supported alkylating activity was evident in lung or liver cytosol.
      SKF 525A and 1-aminobenzotriazole inhibited the NADPH-supported reaction in
      liver, but not lung, while indomethacin and nordihydroguiaretic acid inhibited
      the arachidonic acid-supported reaction in lung but not liver. Cyclophosphamide
      was a moderately active reducing cosubstrate for 5-phenyl-4-pentenyl
      hydroperoxide in both lung and liver microsomes. These results demonstrate that
      pathways in lung tissue unrelated to MFOs can metabolize cyclophosphamide to an
      alkylating compound and that MFO-mediated activation of cyclophosphamide may not
      be essential for the development of the pulmonary toxicity associated with this
      drug.

PMID- 1985773
TI  - Acetylator genotype-dependent expression of arylamine N-acetyltransferase in
      human colon cytosol from non-cancer and colorectal cancer patients.
AB  - Human epidemiological studies suggest an association between rapid acetylator
      phenotype and colorectal cancer. Acetylator genotype-dependent expression by the
      human colon of arylamine N-acetylation capacity, catalyzed by acetyl coenzyme A
      dependent N-acetyltransferase(s) (EC 2.3.1.5) (NAT), may be an important risk
      factor in the initiation of colorectal cancer. Human colon cytosols from 48 fresh
      surgical samples were investigated for NAT activity toward p-aminobenzoic acid
      and the arylamine carcinogens 4-aminobiphenyl, 2-aminofluorene, and beta
      naphthylamine. Apparent Vmax determinations of NAT activity toward these
      substrates indicated that 40 of these colons segregated into 3 distinct
      phenotypes. The distribution of the patients into rapid (5), intermediate (18),
      or slow (17) acetylators is a ratio that is not significantly different from the
      expected Hardy-Weinberg distribution of 3:16:21 (chi 2 = 2.206, P = 0.363).
      Significantly greater mean apparent Vmax levels were found in colons from rapid
      as compared to intermediate acetylators (1.5-3-fold) (P less than 0.001) and
      intermediate as compared to slow (2.5-3-fold) (P less than 0.005) acetylator
      phenotypes for the four arylamine substrates. Apparent Km determinations
      indicated that human colon NAT from rapid acetylators had a significantly lower
      affinity for the arylamine substrates (P less than 0.05) compared to intermediate
      or slow acetylator groups. No difference in apparent Km was detected for the
      cofactor acetyl coenzyme A between the three acetylator phenotypes. The colon
      samples were also tested for cytosolic N-hydroxy-2-acetylaminofluorene
      sulfotransferase activity and found to be monomorphically distributed for this
      enzyme activity. Of the 40 colon samples, 37 were from individuals of known
      pathology, 25 with colorectal cancer and 12 with no diagnosed neoplasia.
      Comparisons between mean apparent Vmax and mean apparent Km levels for each of
      the acetylator phenotypes indicated no significant differences between non-cancer
      and colorectal cancer patients. The distribution of rapid, intermediate, and slow
      acetylator phenotypes among the colon samples derived from colorectal cancer
      patients was precisely that predicted from published frequencies for the rapid
      and slow acetylator allele in Americans of African and European ancestry.

PMID- 1985774
TI  - Endometrial cancer, obesity, and body fat distribution.
AB  - A case-control study was undertaken to evaluate the roles of obesity and body fat
      distribution in the etiology of endometrial cancer. The study also included an
      evaluation of the associations of serum estrone, estradiol, and androstenedione
      with obesity, body fat distribution, and endometrial cancer risk. The study
      included 168 cases and 334 control subjects identified at an optometry clinic. A
      strong, positive relationship between overall obesity and endometrial cancer was
      found. The relative rate of endometrial cancer for women in the upper 90th
      percentile of a body mass index compared to those below the median was estimated
      as 5.5 with 95% confidence limits of 3.2-9.6. There was no association between
      endometrial cancer and the waist to hip ratio, an index of upper versus lower
      body fat distribution. A statistical test of trend across the four quartiles of
      the waist to hip ratio yielded a P value of 0.45 after adjustment for confounding
      by the body mass index. On the other hand, there was a statistically significant,
      independent positive effect of a high subscapular to tricep skinfold ratio, a
      measure of central versus peripheral obesity, on endometrial cancer risk. The
      relative rates of endometrial cancer for the second, third, or fourth quartile
      compared to the first quartile of this index were 1.5, 1.9, and 2.7, respectively
      (P = 0.007), after adjustment for the body mass index. Serum estrone and
      estradiol, but not androstenedione, were statistically significantly correlated
      with the body mass index among control subjects (r = 0.37 and 0.40 for estrone
      and estradiol, respectively). On the other hand, each of the sex hormones was
      uncorrelated with the waist to hip ratio after adjustment for body mass. The
      correlations between each of the three hormones and the subscapular to tricep
      skinfold ratio among controls were weak and were not statistically significant
      (0.10, 0.10, and 0.14 for estrone, estradiol and androstenedione, respectively).
      Cases had statistically significantly higher mean serum estrogen and
      androstenedione levels than did controls and these elevations did not simply
      reflect a higher prevalence of obesity among them. The findings are equivocal
      with respect to fat patterns and endometrial cancer. We suggest that future
      epidemiological studies of cancer and body fat distribution more carefully
      distinguish among the various types of fat patterns.

PMID- 1985775
TI  - Amsacrine-induced lesions in DNA and their modulation by novobiocin and 2,4
      dinitrophenol.
AB  - The cancer chemotherapeutic agent amsacrine, 4'-(9-acridinylamino)-methanesulfon
      m-anisidide (mAMSA), is thought to effect cytotoxicity by inhibiting the ATP
      dependent enzyme topoisomerase II in the act of its duplex strand-passing action.
      Upon protein denaturation, the arrested "cleavable complex" that results gives
      rise to double- and single-strand breaks (dsbs and ssbs) and DNA-protein cross
      links (dpcs). Simultaneous cotreatments with 2,4-dinitrophenol (DNP) or
      novobiocin (novo) abrogates mAMSA cytotoxicity in Chinese hamster cells (H.
      Utsumi et al., Cancer Res., 50:2577-2581, 1990). Pulsed-field gel electrophoresis
      was used to estimate dsbs, velocity sedimentation in alkaline sucrose gradients
      for ssbs, and alkaline elution without protease digestion for dpcs. Although
      cotreatment with DNP or novo modulated somewhat the yield of DNA lesions due to
      mAMSA, quantitatively these changes did not correlate at all with, and therefore
      could not account for, the reduced lethality that resulted from cotreatments. For
      example, DNA cotreatment markedly increased the yields of dsbs, ssbs, and dpcs,
      even though cell killing was appreciably reduced. Furthermore, neither DNP nor
      novo cotreatment affected the rate, or the completeness of, the repair of mAMSA
      induced DNA damage, and neither cotreatment lowered total cellular ATP. Hence,
      the arresting of the cleavable complex by mAMSA, made evident by lesions in DNA,
      did not correlate with cytotoxicity. However, cotreatment with either DNP or novo
      resulted in an enhanced recovery of the mAMSA-induced inhibition of replicative
      DNA synthesis. Because DNP and novo (transiently) slow down DNA synthesis, it is
      proposed that these compounds abrogate mAMSA killing of S phase cells by reducing
      the disorganization of the processing of replicated DNA by topoisomerase II.

PMID- 1985776
TI  - Differential expression of nuclear envelope lamins A and C in human lung cancer
      cell lines.
AB  - The lamins, an intranuclear class of intermediate filament proteins, are major
      structural proteins of the nuclear envelope. In the present study, the three
      abundant mammalian lamins (lamins A, B, and C) were observed to be present in
      roughly equivalent amounts in the Calu-1, Calu-3, H157, and SK-MES-1 non-small
      cell lung cancer lines. In the small cell lung cancer lines OH-1, OH-3, NCI-H82,
      NCI-H209, and NCI-H249, levels of lamin B were similar to those observed in the
      non-small cell lines, but the levels of lamins A and C were diminished by greater
      than or equal to 80%. The relationship between lung cancer phenotype and lamin
      expression was explored further in the NCI-H249 small cell line. Introduction of
      the v-rasH oncogene into this line gives rise to a cell line (NCI-H249rasH) with
      many features of large cell carcinoma of the lung (Falco, J. P., Baylin, S. B.,
      Lupu, R., et al. J. Clin. Invest., 85: 1740-1745, 1990). Concomitant with the v
      rasH-induced change in phenotype, a greater than 10-fold increase in the amounts
      of lamins A and C was observed. Levels of the cytoplasmic intermediate filament
      protein vimentin also increased. In contrast, levels of a variety of nonlamin
      nuclear polypeptides including topoisomerase I, topoisomerase II, poly(ADP
      ribose) polymerase, and the nucleolar protein B23/nucleophosmin did not change.
      Comparison of polyadenylated RNA from NCI-H249 and NCI-H249rasH cells on Northern
      blots revealed similar levels of the mRNA for lamin B but higher levels of the
      mRNAs for lamins A and C in the v-rasH-expressing cell line. These observations
      provide evidence for differences in nuclear envelope structure in histologically
      different neoplastic cells derived from the same epithelial cell system and
      suggest that differences in lamina structure result from phenotype-specific
      differences in lamin gene expression.

PMID- 1985777
TI  - Antineoplastic drug sensitivity of human MCF-7 breast cancer cells stably
      transfected with a human alpha class glutathione S-transferase gene.
AB  - Studies have suggested that the alpha class glutathione S-transferase (GST) may
      protect cells from the chemotherapeutic drugs chlorambucil and melphalan. In
      order to further define the function of human alpha class GST, a complementary
      DNA which encodes it was ligated into an expression vector under the direction of
      the human metallothionein-IIA promoter and stably transfected into human MCF-7
      breast cancer cells in conjunction with the G418-selectable plasmid pSV2neo.
      Clonal cell lines were identified which expressed increased levels of GST enzyme
      activity (2.2- to 5.6-fold). The transfected cell lines also had increased
      peroxidase activity using cumene hydroperoxide as the substrate (1.9- to 3.8
      fold) which is consistent with the intrinsic peroxidase activity of alpha class
      GSTs. Southern blot analysis indicated that genomic DNA from these cells
      contained a fragment indistinguishable from the transfected alpha class GST
      complementary DNA (850 base pairs); Northern blot analysis of total cellular RNA
      indicated that these cells contained appropriately sized alpha class GST RNA (980
      nucleotides); and Western blot analysis indicated that, while MCF-7 cells
      contained no detectable alpha class GST protein, the transfected cells contained
      markedly elevated levels of alpha class GST but no detectable mu or pi class GST.
      These alpha class GST transfected cells had increased resistance to ethacrynic
      acid (2.1- to 3.0-fold). However, the transfected cells failed to show any
      increased resistance measured at the drug dosage which inhibited 50% of the
      colony formation to the chemotherapeutic drugs chlorambucil, melphalan,
      Adriamycin, or cisplatin under conditions of either continuous or 1-h drug
      exposure. Neither was there any change in sensitivity to the cytotoxins
      benzo(a)pyrene, benzo(a)pyrene-trans-7,8-dihydrodiol-9,10-epoxide (anti), or 1
      chloro-2,4-dinitrobenzene. These studies indicate that expression of this human
      alpha class GST by itself in MCF-7 human breast cancer cells does not confer
      resistance to the chemotherapeutic drugs tested under the conditions used in
      these studies.

PMID- 1985778
TI  - pS2 expression and response to hormonal therapy in patients with advanced breast
      cancer.
AB  - Seventy-two patients with advanced breast carcinoma (42% bone, 25% visceral, 5.5%
      soft tissue, and 27.5% multiple site metastases) were evaluated to determine the
      relationship between tumor expression of the estrogen-regulated protein pS2,
      estrogen receptor (ER) or progesterone receptor (PgR) content, and response to
      hormonal therapy. Twenty-nine % of tumors were pS2 positive, 64% were ER
      positive, and 29% were PgR positive. Of the ER-positive patients (n = 43), 15
      (35%) had greater than 10% of the invasive carcinoma which immunostained for pS2
      (these were considered pS2 positive). Only 3 of 24 ER-negative tumors were pS2
      positive. A weak association between pS2 expression and ER content (P = 0.08) but
      not PgR content was observed. Of pS2-positive patients, 52% had a partial or
      complete response to hormonal therapy. In 24% of pS2-positive patients the
      disease stabilized with treatment. In contrast, 27% of pS2-negative patients had
      a partial or complete response. In 10% of these patients the disease stabilized.
      Similar associations between therapeutic response and ER or PgR were not
      observed. The odds of having a clinical response to hormonal therapy was greater
      for pS2-positive than for ER- or PgR-positive tumors. pS2 expression may define a
      subset of ER-positive tumors that are more likely to respond to hormonal
      treatment.

PMID- 1985779
TI  - Genital and urinary tract diseases and bladder cancer.
AB  - The relationship between selected urinary tract and genital diseases and the risk
      of bladder cancer was analyzed using data from a case-control study of 364 cases
      of bladder cancer and 447 controls hospitalized for acute, nonneoplastic,
      nongenital tract conditions, unrelated to known or suspected risk factors for
      bladder cancer. Cystitis was reported by 20% of the cases and 8% of the controls,
      corresponding to a multivariate relative risk (RR) of 3.8 (95% confidence
      interval, 2.4 to 5.9). No association was observed with urinary tract stones (RR
      = 1.2). With reference to genital diseases, the RR was elevated for gonorrhea (RR
      = 2.8, 95% confidence interval, 1.0 to 4.5) and condylomata acuminata (RR = 5.9,
      95% confidence interval 1.0 to 3.6) but not for syphilis. The risk increased with
      the number of episodes of cystitis (RR = 5.0 for greater than or equal to 4
      episodes, chi 2 for trend = 33.04, P less than 0.001), was higher during the last
      15 years after the first episode (RR = 5.1 versus 2.3 for over 15 years), and was
      not heterogeneous across strata of age and sex. The interaction between urinary
      tract infections and tobacco appeared multiplicative, with RR = 2.4 for ever
      smoking, 3.2 for cystitis alone, and 10.3 for both exposures. The present study,
      besides providing further quantitative evidence of a relationship between urinary
      tract infections (and, possibly, some genital infections, too) and bladder
      cancer, indicates that the role of infections is probably in one of the latter
      (promoting) stages of the process of carcinogenesis and suggests a multiplicative
      interaction with smoking. In terms of prevention and public health, therefore, it
      is thus important to avoid at least one exposure for subjects with a history of
      urinary tract infections who smoke tobacco.

PMID- 1985780
TI  - Tumor-promoting phorbol ester and activated Ha-ras synergistically reduce the
      interleukin 3 requirement in a mast cell line.
AB  - Infection of the bone marrow-derived mast cell line PB-3c with a retrovirus
      carrying oncogenic c-Ha-ras or v-Ha-ras reduced the interleukin 3 (IL-3) growth
      requirement and induced a state of tumorigenicity. In contrast, normal c-Ha-ras
      had no effect on the IL-3 requirement of this cell line nor did the cells become
      tumorigenic. A factor reduction similar to that caused by activated Ha-ras was
      transiently obtained with 12-O-tetradecanoylphorbol-13-acetate in the PB-3c cells
      expressing normal c-Ha-ras. The analogous stimulation of protein kinase C (PKC)
      in PB-3c cells producing oncogenic Ha-ras led to an additional reduction of the
      IL-3 requirement during the first 24 h. In the absence of IL-3, the prolonged
      exposure of the cells to 12-O-tetradecanoylphorbol-13-acetate for 72 h resulted
      in a stimulation of growth when activated but not when normal Ha-ras was
      expressed. PB-3c cell lines expressing activated Ha-ras neither revealed
      differences in the amounts nor in the subcellular distribution of PKC activity
      but displayed elevated levels of immunoreactive beta-PKC compared to the parental
      PB-3c cells. Upon 12-O-tetradecanoylphorbol-13-acetate treatment, a protracted
      down-regulation of the immunodetectable alpha-PKC as well as constitutively high
      levels of c-fos mRNA were observed when oncogenic Ha-ras was expressed. These
      data suggest the involvement of specific PKC subtypes and of c-fos in the
      reduction of the IL-3 requirement caused by activated Ha-ras in this particular
      hematopoietic cell line.

PMID- 1985781
TI  - Numerical chromosome 1, 7, 9, and 11 aberrations in bladder cancer detected by in
      situ hybridization.
AB  - Forty transitional cell carcinomas of the human urinary bladder (TCCs) were
      examined for numerical aberrations of chromosomes 1, 7, 9, and 11 by in situ
      hybridization using chromosome-specific probes. Our interphase cytogenetic study
      of 24 low-grade, noninvasive TCCs, which were near-diploid by flow cytometry,
      showed a numerical aberration for at least 1 of these chromosomes in 14 of these
      cases. Most strikingly, a monosomy for chromosome 9 was found in 9 of 24 low
      grade TCCs. A trisomy for chromosomes 1, 7, and 11 was detected in 5, 2, and 1
      case(s), respectively. In 1 case a monosomy for chromosome 1 was detected by in
      situ hybridization. Monosomy for chromosome 9 was the only detected numerical
      change in 5 low-grade TCC cases. Examination of 16 invasive TCCs showed extra
      copies for chromosomes 1 and 7 in 7 flow cytometrically diploid cases with
      numerical chromosome aberrations; also, loss of chromosome 9 was detected. In 5
      invasive and 2 noninvasive aneuploid/tetraploid TCCs a profound imbalance between
      the different chromosomes was found. In 5 of these cases an evident
      underrepresentation of chromosome 9 in comparison to chromosomes 1, 7, and 11 was
      detected. This underrepresentation of chromosome 9 in diploid, as well as
      aneuploid, TCCs, and in some cases the constant ratio between this chromosome and
      the other chromosomes, may be explained by a process of tetraploidization.
      Therefore, loss of chromosome 9 may be one of the primary genetic events in TCC
      oncogenesis, with secondary events, such as tetraploidization, correlated to
      tumor progression. Our results show that in situ hybridization can be routinely
      used to study important cytogenetic changes which occur during the development of
      a malignant disease.

PMID- 1985782
TI  - Class I major histocompatibility complex enhancement by recombinant leukocyte
      interferon in the peripheral blood mononuclear cells and plasma of melanoma
      patients.
AB  - In vivo administration of escalation doses of recombinant alpha-interferon (IFN
      alpha) during a phase I trial in malignant melanoma patients caused dose
      dependent increases in the mRNA accumulation, synthesis, steady state cellular
      content, and plasma membrane expression of class I major histocompatibility
      complex molecules in peripheral blood mononuclear cells. In addition, circulating
      levels of class I molecules were also enhanced. These findings show that (a)
      antigenic enhancement by biomodifiers may occur in vivo, in humans and (b) the
      mechanism of class I major histocompatibility complex enhancement by IFN-alpha is
      similar in vitro and in vivo. Furthermore, because peripheral blood mononuclear
      cells of different melanoma patients display different susceptibility to IFN
      alpha, the entity of their antigenic modulation may represent a useful parameter
      to evaluate the efficacy of different therapeutic regimens and/or assess the
      individual susceptibility to the molecular changes induced by IFN-alpha.

PMID- 1985783
TI  - Use of the lectin from Amaranthus caudatus as a histochemical probe of
      proliferating colonic epithelial cells.
AB  - A newly isolated lectin, Amaranthus caudatus agglutinin (also called amaranthin
      or ACA), which binds to the Thomsen-Friedenreich antigen (T-antigen) and its
      sialylated variants, was used as a histochemical probe for proliferating cells in
      sections of human colonic tissues. Binding inhibition studies revealed that ACA
      binds to different sites on histological sections when compared to peanut
      agglutinin, which also recognizes the T-antigen. ACA bound selectively to the
      cells at the base of the colonic crypt [46 +/- 4% (SEM) of glands] which is the
      zone of proliferation in this tissue and preferentially labeled cytoplasmic and
      apical membrane glycoconjugates. Only 7 +/- 2% of the upper portions of the
      colonic crypts were labeled (P less than 0.001 compared to the base), and this
      was largely a result of extensive labeling in 2 of 23 samples studies. A marked
      increase in histochemical labeling by ACA was seen in adenomatous polyps and
      adenocarcinomas of the colon, in which 82 +/- 7 and 97 +/- 2% of the glandular
      units were labeled, respectively. Transitional mucosa and connective tissue
      adjacent to cancers were also labeled by ACA. Neuraminidase studies indicated
      that removal of sialic acid residues enhanced binding by peanut agglutinin, but
      not ACA, to glycoconjugates in cancer specimens. Specimens of colonic tissue from
      patients with familial adenomatous polyposis (FAP) were examined with ACA; 83 +/-
      7% of adenomatous glands and 60 +/- 7% of glands in flat, normal-appearing tissue
      were labeled. Colonic tissues from persons at 50% risk for hereditary
      nonpolyposis colorectal cancer (HNPCC), FAP, and normal colons were studied and
      given "weighted average" labelling scores that ranged from 0-400 to accommodate
      variable intensity and distribution of labeling. Normal colons had a weighted
      average score of 65 +/- 33; FAP tissues had a score of 224 +/- 76 (P less than
      0.001 compared to normal colon) and HNPCC tissues had a score of 74 +/- 70 (P
      less than 0.05 compared to normal colon). A group of five HNPCC cases had scores
      of 203 +/- 43 (P less than 0.001 compared to normal colon). ACA labels
      glycoconjugates in the proliferative region of normal human colonic epithelium
      and neoplastic lesions of the colon. The results of FAP and HNPCC tissues suggest
      that it may be useful for identifying foci of abnormal proliferation in familial
      colorectal cancer syndromes.

PMID- 1985784
TI  - Increased susceptibility of aged rats to hepatocarcinogenesis by the peroxisome
      proliferator nafenopin and the possible involvement of altered liver foci
      occurring spontaneously.
AB  - We investigated the mechanism of the hepatocarcinogenic action of nafenopin
      (NAF), a nongenotoxic peroxisome proliferator. Groups of male rats aged 13 wk
      (designated "young") or 57 wk (designated "old") were fed NAF for 13 mo;
      additional groups received a basal diet or a phenobarbital (PB)-containing diet
      as positive control. The following results were obtained. (a) NAF produced
      numerous hepatocellular adenomas and carcinomas in old animals but very few in
      young animals. A similar result, although less pronounced, was seen with PB.
      Adenomas of PB-treated groups mostly consisted of eosinophilic and glycogen
      storing cells. However, adenomas and carcinomas of NAF-treated livers were
      composed of weakly basophilic cells. (b) Phenotypically altered foci, evaluated
      in hematoxylin:eosin-stained sections, appeared spontaneously in untreated
      livers. The majority of these foci was either of the eosinophilic-clear cell or
      the tigroid cell type. In addition, we identified foci which are characterized by
      weak, diffuse cytoplasmatic basophilia. Their phenotype was similar to that of
      adenomas and carcinomas in NAF-treated rats. The number and size of eosinophilic
      clear cell and of tigroid cell foci increased considerably with the age of the
      animals. At the end of the experiment, approximately 2.4% of liver tissue was
      occupied by focal cells. NAF, but not PB, treatment led to a selective increase
      in number and size of weakly basophilic foci. This subtype has previously been
      described as a likely precursor lesion for liver tumors induced by an aflatoxin
      B1-NAF initiation-promotion regimen (B. Kraupp-Grasl et al., Cancer Res., 50:3701
      3708, 1990). These findings suggest that the peroxisome proliferator NAF leads to
      tumor development in aging rat liver by promotion of spontaneously occurring
      preneoplastic lesions. The type of lesion appears to be different from that
      promotable by PB.

PMID- 1985785
TI  - Successful treatment of murine melanoma with bryostatin 1.
AB  - Bryostatins are a novel class of protein kinase C activators which were isolated
      from the marine bryozoan Bugula neritina and found to possess both antineoplastic
      and immunoenhancing properties. In this report, we examined the relationship
      between the in vivo and in vitro antineoplastic effects of bryostatin 1. The in
      vivo antitumor activity of bryostatin 1 was demonstrated in a B16 melanoma
      pulmonary metastases model, in which treatment of tumor-bearing C57BL/6 mice with
      5 days of bryostatin 1 resulted in a significant reduction in of the number of
      lung nodules (control, 87; bryostatin, 7). There was a clear dose-response
      effect, with the optimal antimelanoma dose being 100 micrograms/kg/day, but even
      low doses of bryostatin 1 of 1 micrograms/kg/day resulted in a 53% reduction in
      the number of metastases. Although bryostatin 1 shares many biological properties
      with the phorbol esters, parallel treatment with 12-O-tetradecanoyl 13-phorbol
      acetate was ineffective against B16 melanoma in vivo. Using a clonogenic assay,
      bryostatin 1 was found to have a direct antiproliferative effect against B16
      melanoma. This inhibition occurred at relatively high bryostatin 1 concentrations
      (10(-6) M), in comparison with a sensitive cell line REH (10(-10) M). Treatment
      of mice with bryostatin 1 or preincubation of normal spleen cells with bryostatin
      1 failed to enhance nonspecific cell-mediated cytotoxicity against B16 melanoma
      in vitro. Moreover, bryostatin 1 was found to inhibit both natural killer cell
      activity and interleukin 2 generation of lymphokine-activated killer cells. Thus,
      a role for an in vivo immune enhancement mechanism as the basis for the
      antimelanoma activity observed with bryostatin 1 cannot be invoked from these
      experiments. These findings indicate that bryostatin 1 may act directly on the
      B16 melanoma pulmonary metastases. The precise mechanism whereby bryostatin
      exerts its antimelanoma effects remains unclear.

PMID- 1985786
TI  - Direct intralymphatic injection of radiolabeled 111In-T101 in patients with
      cutaneous T-cell lymphoma.
AB  - Direct intralymphatic administration of radiolabeled monoclonal antibody in
      targeting antigen-bearing lymphoma cells in regional lymph nodes of patients with
      cutaneous T-cell lymphoma was evaluated. Seven consecutive patients undergoing
      staging lymphangiography received intralymphatic infusions of 111In-T101 to
      evaluate lymph node involvement. This procedure was accomplished without
      significant complication. The 111In-T101 rapidly distributed throughout the
      regional lymphatic compartment and passed into the systemic circulation. Tumor
      bearing sites in the inguinal-femoral lymph nodes retained from 0.42 to 4.8% of
      the injected dose of radiolabeled antibody. Three patients were upstaged to Stage
      IVA based on tumor involvement found after radiolymphoscintigraphy-directed
      biopsy of groin lymph nodes, selected because of intense radioactivity by gamma
      camera imaging. Compared with previously reported s.c. antibody administration,
      there was a marked reduction in the radioactive exposure of normal tissues at the
      injection sites in the lower extremities. Direct intralymphatic delivery of 111In
      T101 appears to be a feasible, efficient method for delivering therapeutic doses
      of radiolabeled antibody.

PMID- 1985787
TI  - Interaction of hyperthermia and cis-diamminedichloroplatinum(II) alone or
      combined with radiation in a C3H mammary carcinoma in vivo.
AB  - The interaction between hyperthermia and cis-diamminedichloroplatinum(II) (c-DDP)
      given in various schedules as an adjuvant to radiation treatment was investigated
      in a C3H mouse mammary carcinoma in vivo. Both hyperthermia (43.5 degrees C for
      60 min) and c-DDP (6 mg/kg i.p.) caused a delay in tumor growth when given
      individually. When c-DDP was given 4 h prior to hyperthermia, the increase in
      tumor growth time corresponded to an additive effect, but when the interval was
      reduced to 15 min, the tumor growth delay was significantly greater than
      additive. The modifying effect of these schedules on radiation was studied using
      local tumor control (50% tumor control dose) as the endpoint. c-DDP alone did not
      result in any enhancement of tumor control, irrespective of whether it was given
      15 min or 4 h after irradiation. In contrast, heat treatment at 43.5 degrees C
      for 60 min given 4 h after irradiation resulted in a significant reduction in the
      50% tumor control dose, with an enhancement ratio of 1.8. From a clamped local
      tumor control assay, it was found that c-DDP selectively killed aerobic cells,
      whereas hyperthermia was primarily directed toward the hypoxic clonogenic cells
      in the tumors. Combining the two modalities (simultaneously) resulted in a
      significant additional increase in the killing of well-oxygenated clonogenic
      cells, but the destruction of hypoxic cells was not different from that obtained
      after heat alone.

PMID- 1985788
TI  - Inhibition of cell growth by lovastatin is independent of ras function.
AB  - We have investigated the inhibition of cell growth by lovastatin (previously
      known as mevinolin), an antagonist of hydroxymethylglutaryl coenzyme A reductase
      which blocks the processing and membrane localization of ras proteins via
      inhibition of polyisoprenylation. A series of NIH 3T3 cells transformed by
      oncogenes with activities that are dependent or independent of isoprenylated ras
      were studied, including cells transformed by myristylated ras protein that is
      isoprenylation independent. Treatment with lovastatin at concentrations ranging
      from 5 to 15 microM for up to 96 h resulted in a time- and dose-dependent
      inhibition of cell growth in all lines tested. The inhibition ranged from 25 to
      50% when cells were treated with 5 microM lovastatin for 48 h, to 72-90% for
      cells treated with 15 microM lovastatin for 96 h. Cells transformed by c-ras, v
      ras, v-src, v-raf, and the myristylated ras genes displayed similar
      sensitivities; the parental NIH 3T3 line was the most resistant of the lines
      tested. Metabolic labeling of control and lovastatin-treated cells with
      [35S]methionine or tritiated lipids revealed that 15 microM lovastatin blocked
      the processing of both endogenous ras and v-ras proteins yet had no effect on the
      lipidation of myristylated ras proteins. Addition of 300 microM mevalonic acid
      overcame the inhibition induced by 15 microM lovastatin. Thus the inhibition of
      cell growth in vitro by lovastatin did not show specificity for cells the
      transformation of which is dependent upon isoprenylated ras protein. It is
      therefore likely that the inhibition of other pathways affected by lovastatin,
      such as cholesterol biosynthesis or the processing of other cellular proteins,
      are responsible for the growth inhibition by lovastatin.

PMID- 1985790
TI  - Intravesical administration of radiolabeled antitumor monoclonal antibody in
      bladder carcinoma.
AB  - Tumor associated AUA1 monoclonal antibody and 11.4.1. nonspecific monoclonal
      antibody, which does not react with human tissues, were radiolabeled with 111In
      and administered intravesically to 23 patients undergoing cystoscopy for bladder
      carcinoma. The antibody solution remained in the bladder for 1 h and then was
      washed out prior to cystoscopy. Tumor and nontumor samples were obtained during
      cystoscopy and were counted in a gamma counter. Conventional and immunoperoxidase
      staining with both antibodies were also performed. AUA1 reacted with all bladder
      carcinomas while 11.4.1. was negative in all cases. The mean uptake of AUA1 at 2,
      24, and 48 h after the instillation (expressed as 10(3) x percentage of injected
      dose/g of tissue) was: 6.12 +/- 5.50 (SD), 1.70 +/- 2.57, 0.30 +/- 0.17 in the
      tumors and 0.32 +/- 0.50, 0.22 +/- 0.30, 0 in the nontumor areas, and for 11.4.1.
      it was: 0.075 +/- 0.075, 0.025 +/- 0.025 in the tumors and 0.30 +/- 0.42, 0.15 +/
      0.26 in the nontumor areas. The uptake of AUA1 by the tumors correlated with the
      tumor grade. There was no radioactivity in the blood at 2 h, and at 1, 2, and 3
      days after the instillation. Our results indicate that intravesical
      administration of radiolabeled monoclonal antibody AUA1 targets selectively to
      tumor tissue without any significant normal tissue uptake. This finding might
      allow the development of a nontoxic and specific therapeutic approach for
      superficial bladder carcinoma.

PMID- 1985789
TI  - Beta 1-6 branched oligosaccharides as a marker of tumor progression in human
      breast and colon neoplasia.
AB  - Malignant transformation of murine and human cells is commonly associated with
      increased--GlcNAc beta 1-6Man alpha 1-6Man beta--branching in asparagine-linked
      oligosaccharides. Somatic mutations and drugs which block expression of the beta
      1-6 branched oligosaccharides are potent inhibitors of tumor cell invasion and
      metastasis in animal models. This suggests that the oligosaccharides are required
      for metastasis to occur and therefore their increased presence in primary tumors
      may be diagnostic of metastatic disease. Although antibodies to the beta 1-6
      branched portion of the oligosaccharides are not available, a plant lectin
      leukoagglutinin (L-PHA) has been shown to bind specifically to this structure. L
      PHA lectin histochemistry was performed on paraffin sections of human breast and
      colon tissues. All breast carcinomas and epithelial hyperplasia with atypia
      showed significantly increased L-PHA staining compared to fibroadenomas and
      hyperplasia without atypia. In histological sections of colon, adenomas showed a
      small but significant increase in L-PHA staining compared to normal colonic
      epithelium, while carcinomas showed greatly increased reactivity. In addition,
      Dukes stage C tumors showed higher levels of L-PHA staining than stage A tumors.
      These results demonstrate that L-PHA-reactive beta 1-6 branched N-linked
      oligosaccharides are consistently increased in neoplasias of human breast and
      colon and that the level of L-PHA staining correlates with the pathological
      staging of the diseases.

PMID- 1985791
TI  - Influence of major histocompatibility complex class I and II antigens on survival
      in colorectal carcinoma.
AB  - HLA-A,B,C and HLA-D molecules present antigenic peptides to the antigen-specific
      receptor of autologous T-lymphocytes. T-cell-mediated host-versus-tumor response
      might therefore depend on the presence of these molecules on tumor cells,
      although the absence of HLA-A,B,C determinants on a cell has been shown to
      increase its susceptibility to lysis by natural killer cells. To investigate
      whether the presence or absence of HLA-A,B,C and/or HLA-DR in colorectal
      carcinoma influences relapse rate and time of tumor-related death, 152 patients
      who underwent putatively curative surgical treatment were surveyed for a maximum
      of 65 months (mean, 48 months). As determined by immunohistochemistry, aberrant
      reduction or loss of HLA-A,B,C/beta 2-microglobulin molecules was more frequent
      in tumors of the proximal colon than of the rectosigmoid (P = 0.032) and in
      mucinous carcinomas than in nonmucinous ones (P = 0.022). An abnormal induction
      of the HLA-D-associated invariant chain (Ii) was more frequent in Dukes' A and B
      than in stage C (P = 0.046). Reduction/loss of HLA-A,B,C/beta 2-microglobulin was
      correlated with the absence of HLA-DR (P = 0.024) and Ii (P = 0.005). In contrast
      to the prognostic role of tumor stage and grade, the presence versus the absence
      of HLA-A,B,C/beta 2-microglobulin and HLA-DR/Ii molecules was not correlated with
      recurrence rate or survival. We conclude that in spite of an increasing amount of
      experimental data suggesting the contrary, the status of HLA-A,B,C and HLA-DR
      expression in colorectal carcinoma seems to be irrelevant in vivo, regarding
      survival and growth of residual tumor cells after putatively curative resection
      of the initial tumor burden.

PMID- 1985792
TI  - Induction of internucleosomal DNA fragmentation in human myeloid leukemia cells
      by 1-beta-D-arabinofuranosylcytosine.
AB  - The present results demonstrate that treatment of human U-937 myeloid leukemia
      cells with 1-beta-D-arabinofuranosylcytosine (ara-C) is associated with DNA
      fragmentation at multiples of approximately 200 base pairs. The extent of ara-C
      induced DNA fragmentation was dependent on drug concentration and time of
      exposure. This pattern of internucleosomal DNA cleavage has been observed during
      programmed cell death and was associated in the present studies with loss of
      clonogenic survival. The results also demonstrate that the c-jun protooncogene is
      induced by ara-C during periods of DNA cleavage. These findings suggest that ara
      C activates a program involving both oligonucleosomal DNA fragmentation and
      changes in early response gene expression.

PMID- 1985793
TI  - Re: S. Pulciani et al., Detection of a transforming gene in spontaneous reticulum
      cell sarcoma of SJL/J mice: genetically linked and host-dependent neoplasia.

PMID- 1985794
TI  - Tenth annual Sapporo cancer seminar. Recent topics in cancer research.

PMID- 1985795
TI  - AIDS virus infection and autoimmunity: a perspective of the clinical,
      immunological, and molecular origins of the autoallergic pathologies associated
      with HIV disease.
AB  - The acquired immune deficiency syndrome (AIDS) is a viral-induced disorder of
      humans that is reaching pandemic proportions. The etiologic agent responsible for
      AIDS is recognized as a retrovirus termed the human immunodeficiency virus (HIV).
      This virus is both cytotropic and cytopathic for T lymphocytes in vitro, and
      patients with AIDS and HIV-related conditions invariably have serious T cell
      abnormalities, notably a reduced number of the helper/inducer (CD4+)
      subpopulation. There is now a substantial body of evidence to suggest that the
      AIDS virus triggers a diverse range of autoimmune phenomena. The purpose of this
      article is to summarize the clinical and immunopathological manifestations of
      autoimmunity in HIV infection and to provide a perspective of the possible
      origins and roles autoimmune reactions play in HIV disease progression.

PMID- 1985796
TI  - An antibody reacting with splenic red pulp macrophages in the sera of patients
      with rheumatic diseases.
AB  - An antibody was detected in the sera of patients with certain rheumatic diseases
      that reacted with the cytoplasm of the splenic red pulp (SRP) cells of adult
      mice. This antibody was detected in the sera of all patients with mixed
      connective tissue disease (MCTD), 53% of patients with systemic lupus
      erythematosus (SLE), 42% with Sjogren's syndrome (SS), and 10% with rheumatoid
      arthritis (RA). However, this antibody was found neither in the sera from
      patients with other types of rheumatic diseases nor in healthy volunteers. The
      screening of this antibody may be useful in diagnoses of MCTD, SLE, and SS. In
      the present study, we also performed the characterization of the cells reacting
      with this antibody. The cells proved to be acid phosphatase positive phagocytes
      in the SRP, that is, red pulp macrophages. Moreover, a histochemical analysis of
      the reacting antigen in these cells has demonstrated that its antigenic activity
      is NaIO4 and RNase sensitive, suggesting that the antigen may be associated with
      RNA.

PMID- 1985797
TI  - IgG subclass responses to human immunodeficiency virus-1 antigens: lack of IgG2
      response to gp41 correlates with clinical manifestation of disease.
AB  - To analyze differential antibody responsiveness of potential pathogenetic
      significance, sera from 66 patients with human immunodeficiency virus-1 (HIV-1)
      infections at various Walter Reed (WR) stages of the disease were analyzed to
      determine the subclass distribution of HIV antibodies. Although all IgG
      subclasses were involved in the HIV antibody response, the frequency was highest
      for IgG1 and the lowest for IgG4. When IgG subclass responses to different HIV
      antigens were compared qualitatively, IgG1 was the major subclass reactive with
      env, pol, and gag antigens; IgG2 and IgG3 were almost equally represented in
      response to gag gene products; and IgG4 showed minimal reactivity to p24 antigen
      in all HIV-infected patients regardless of their clinical presentation. In
      contrast, significantly lower levels of IgG2 anti-gp41 were observed in patients
      at WR 5 and 6 (5%) when compared to those at stage WR 1 and 2 (88%). The IgG2
      response to a recombinant gp 120/41 antigen, however, remained unchanged,
      suggesting that the lack of IgG2 response may be associated with lack of
      responsiveness to the carbohydrate epitope on gp41. Indeed, parallel measurements
      of IgG antibody responses to group A carbohydrate were also lower in patients at
      WR 5 and 6 stages, without affecting antibody responses to polyribosyl ribitol
      phosphate and phosphocholine. As antibody responses to group A carbohydrate with
      its N-acetyl D-glucosamine (GlcNAc) determinant were lower at the WR 5 and 6
      stage of HIV disease, GlcNAc may be one of the antigenic determinants on gp41
      that plays a critical role in some of the pathologic events of HIV infection.

PMID- 1985798
TI  - Increased susceptibility to in vitro ultraviolet B radiation in fibroblasts and
      lymphocytes cultured from systemic lupus erythematosus patients.
AB  - Sunlight is known to induce exacerbations of systemic lupus erythematosus (SLE)
      but its mechanism remains unclear. We have previously reported that ultraviolet A
      (UVA) exposure induces an increase in total DNA synthesis (DS) in vitro but a
      decrease in unscheduled DNA repair synthesis (UDRS) of splenocytes of murine SLE
      strains. In order to investigate whether similar observations are characteristic
      of human SLE, peripheral blood lymphocytes (PBL) and dermal fibroblast (DF)
      cultures of 20 patients and 15 matched controls were exposed in vitro to UVA or
      UVB at different doses. Thirteen (65%) SLE DF cultures exposed to UVB light (12
      24 J/m2) showed an increase in DS compared to paired unirradiated cultures. In
      contrast, UVB-irradiated DF from normal individuals had no significant increase
      in DS following UVB irradiation. When SLE DF were exposed to higher doses of UVB
      (48-96 J/m2), 90% of cultures showed a decrease in DS compared to only 20% in the
      control group. All of the SLE DF cultures showed a decrease of their unscheduled
      DNA repair capacity following UVB (24-48 J/m2) irradiation whereas no UDRS was
      apparent in 74% of controls under the same conditions. Similar findings regarding
      UDRS were observed in SLE PBL cultures and were also confirmed by
      autoradiography. UVA exposure (0-3840 J/m2) had no effect on DS nor on UDRS in DF
      or PBL cultured from SLE and controls. The relevance of these in vitro findings
      to the in vivo pathogenesis of the disease is discussed.

PMID- 1985799
TI  - [Significance of electro- and echocardiogram for the diagnosis of cardial
      amyloidosis].
AB  - The cause of severe right heart failure and of equal diastolic pressures in both
      ventricles (as seen in constrictive pericarditis) in a 56-year-old woman was
      suspected to be cardiac amyloidosis on the basis of findings in both the
      echocardiogram (biventricular hypertrophy) and the electrocardiogram (prominent Q
      waves, absent hypertrophy signs). The endomyocardial biopsy was at first
      unremarkable. But later, serial modified Congo-red staining unequivocally
      demonstrated amyloid deposits. In a second case, a 66-year-old man with global
      cardiac failure and echocardiographic pointers towards hypertrophic
      cardiomyopathy, was treated with verapamil, 240 mg daily. When this was not
      tolerated he was hospitalized. He, too, had prominent Q waves but no signs of
      ventricular hypertrophy. Cardiac amyloidosis was confirmed by biopsy. Both cases
      underline the special importance of echo- and electrocardiographic changes, taken
      together, in the diagnosis of cardiac amyloidosis.

PMID- 1985800
TI  - [Destructive spondylarthropathy in dialysis patients].
AB  - Back pain and a cervicobrachial syndrome, as well as progressive sensory and
      motor deficits as far as symptoms of paraplegia, developed in two dialysis
      patients two and five years after the start of dialysis. One was a 60-year-old
      woman with pyelonephritis, the other a 55-year-old man with glomerulonephritis.
      There were typical radiological signs of destructive spondylarthropathy (narrowed
      intervertebral spaces and slippage of the vertebral bodies). The female patient
      required several operations (spondylothesis and orthothesis) and both patients
      received daily 10,000 IU vitamin D and 3-4 g calcium carbonate. In the woman the
      destructive process no longer progressed one year after onset of symptoms, but
      she still required many analgesics. She died three months later of circulatory
      failure. The man died four weeks after the onset of symptoms from purulent
      meningitis. At autopsy only renal fibrous ostitis was still demonstrable.
      Amyloidosis resulting from an increase in beta 2-microglobulin level were
      excluded by both histological and immunohistochemical examinations.

PMID- 1985801
TI  - [The von Hippel-Lindau syndrome].

PMID- 1985802
TI  - [Ambroise Pare on the 400th anniversary of his death].

PMID- 1985803
TI  - [Scintigraphic diagnosis of coronary heart disease].

PMID- 1985804
TI  - [Sports and the digestive tract].

PMID- 1985805
TI  - [Smoking and physicians].

PMID- 1985806
TI  - [The significance of laboratory findings in long-term antiepileptic therapy].
AB  - A retrospective study of 316 patients (173 men, 143 women; mean age 39 [17-87]
      years) who had taken antiepileptics (phenytoin, phenobarbital, carbamazepine,
      valproic acid) for at least six months, was carried out to assess the biochemical
      and haematological changes in relation to the drug used, the therapeutic
      programme and the drug serum levels. The most frequent change was isolated
      elevation of gamma-GT (9-89% of cases depending on the drug), followed by
      elevation of alkaline phosphatase (16-44%). Increases in the transaminases GOT (4
      13%) and GPT (4-19%) were infrequent and minor. Changes in the blood picture were
      very infrequent and never more than minimal. Correlation between all these
      changes and serum drug levels was poor (r less than 0.15). Correlations between
      drug serum level and dose were found in the case of phenobarbital (r = 0.6) and
      valproic acid (r = 0.5). There was hence no evidence of any clear connection
      between the biochemical findings and the serum concentrations of antiepileptic
      drugs or their-dosage. The results indicate that undue importance has previously
      been attached to routine checks of biochemical parameters; abnormal biochemical
      findings by themselves are not usually enough to necessitate changes in
      treatment. Determination of biochemical and haematological parameters is
      necessary only if there are clinical grounds for it such as suspicion of side
      effects, the occurrence of epileptic attacks despite therapy, or change from one
      drug to another.

PMID- 1985807
TI  - [Carboxyhemoglobin in smokers and a preoperative smoking cessation].
AB  - The proportion of carbon monoxide-haemoglobin (COHb) in blood was determined
      before elective surgery on 50 patients (12 women and 38 men; mean age 39.5 [21
      68] years) who were smoking at least 20 cigarettes a day, at two moments: during
      ad lib smoking and after a smoking halt of more than nine hours. 50 nonsmokers
      (25 women and 25 men; mean age 29.5 [20-48] years) served as controls. COHb
      proportion before smoking halt averaged 6.9 +/- 1.8%, after halt it averaged 3.8
      +/- 1.1% (P less than 0.001). Individual values over 6% were found even after
      abstinence. COHb proportion in nonsmokers was 1.8 +/- 0.2% (nonsmokers vs.
      smokers: P less than 0.001 with and P less than 0.01 without smoking halt). The
      results show that measures to improve oxygen transport capacity, such as blood
      transfusion or oxygen breathing, are indicated early, especially in an emergency,
      in smokers and those with uncertain smoking habits. Smoking halt of at least nine
      hours should be recommended to all heavy smokers before elective surgery.

PMID- 1985808
TI  - [Unilateral sacroiliitis in multiorgan tuberculosis].
AB  - A tight but painless soft-tissue swelling in the left parasternal region, with
      chronic cough and lumbo-ischial pain becoming progressively more severe over
      several months, occurred in a 27-year-old man. The chest X-ray film was normal,
      radiography of the iliosacral joints revealed right-sided sacroiliitis. In the
      further course of the illness night sweat, nightly fever up to 38 degrees C and
      weight loss of 7 kg in two months, as well as severe treatment-resistant earache
      developed. When hospitalized, another chest X-ray film showed disseminated small
      nodular foci pointing to tuberculosis. Sputum and irrigation fluid from the right
      middle-ear contained Mycobacterium tuberculosis. Biopsy material from the
      parasternal tumour and middle-ear mucosa contained caseous granulomas, confirming
      the diagnosis of tuberculous sacroiliitis as part of multi-organ tuberculosis.
      Tuberculostatic treatment--400 mg isoniazid, 600 mg rifampicin, and 1,500 mg
      pyrazinamide daily (the latter discontinued after 8 weeks)--normalized the
      appearance in the chest X-ray film. The patient returned to his home in Holland
      and, four years later, reported that he was free of any symptoms, even during
      sport activity.

PMID- 1985809
TI  - [Loading-induced ST-interval elevations in the case of normal coronary arteries.
      The angiographic demonstration of loading-induced coronary artery spasm].
AB  - In a 60-year-old man with exercise-dependent anginal symptoms, reversible ST
      segment elevations of maximally 0.8 mV occurred in the anterior chest leads
      during ergometric exercise at 75 W. Angiography excluded coronary artery
      stenoses. To demonstrate whether he had exercise-dependent vasospastic angina,
      angiography was performed during bicycle ergometry. At 75 W the typical symptoms
      recurred, accompanied by ST elevations in the ECG. At the same time, spasm in the
      region of the anterior interventricular branch was demonstrated angiographically;
      it disappeared at once after intracoronary injection of 200 micrograms
      nitroglycerin. The patient subsequently remained free of symptoms while taking
      isosorbide dinitrate (120 mg daily) and nifedipine (80 mg daily).

PMID- 1985810
TI  - [Allogeneic bone marrow transplantation. The prerequisites, indications and
      results].

PMID- 1985811
TI  - [The immunopathophysiology of burn trauma].

PMID- 1985812
TI  - [Recruitment by a general hospital and the assumption of the title "chief
      physician" by a staff physician].

PMID- 1985813
TI  - [The fitness of dialysis patients to drive a motor vehicle].

PMID- 1985814
TI  - [A fatal complication in percutaneous endoscopic gastrostomy].

PMID- 1985815
TI  - [The diagnosis of thyroid carcinoma].

PMID- 1985816
TI  - [Endothelin-1 in umbilical cord blood].

PMID- 1985817
TI  - Ontogenetic features of audiogenic seizure susceptibility induced in immature
      rats by noise.
AB  - Although numerous models are currently used for systematic study of the
      mechanisms of epileptogenesis in mature brain, few animal models have been
      developed that allow similar explorations in the developing nervous system. One
      experimental model of epilepsy supports a premise that perinatal experience can
      lead to eventual seizure susceptibility, however. Audiogenic seizure (AGS)
      susceptibility can be induced during a critical developmental period in normal
      mice by auditory deprivation and therefore by cochlear trauma. We studied the
      developmental parameters that affect success of both induction and testing of AGS
      susceptibility in the rat. Intense high-frequency noise exposure was used as the
      traumatizing agent. The Wistar rat strain used is inherently seizure-resistant
      because in greater than 400 trials, untreated rats have never exhibited
      susceptibility at any age. Although single prolonged exposures to high-intensity
      noise were administered to groups of rats at ages between postnatal days (PNDs)
      12 and 36, PND 14 was the age when exposure was most likely to result in eventual
      seizure susceptibility. Furthermore, duration of initial exposure on PND 14
      determined the rate of susceptibility when measured 2 weeks later. Accordingly,
      we noted that single noise exposures at an intensity of 125 dB and ranging
      between 6 and 10 min in duration induced susceptibility in 100% of rats tested on
      PND 28; nonetheless, seizures among the rats exposed for 8 min were the most
      severe. Typically, these seizures began as wild running attacks and were followed
      by tonic/clonic convulsions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1985818
TI  - Effects of discontinuation of phenytoin, carbamazepine, and valproate on
      concomitant antiepileptic medication.
AB  - We report a prospective, controlled study of the effects of the reduction and
      discontinuation of phenytoin (PHT) (22 patients), carbamazepine (CBZ) (23
      patients), and valproate (VPA) (25 patients) with concomitant antiepileptic drugs
      (AEDs). The principal changes in the serum concentrations of concomitant AEDs
      were (a) phenobarbital (PB) concentrations decreased by a mean of 30% on
      discontinuation of PHT; (b) total CBZ concentrations increased by a mean of 48%
      and free CBZ concentrations increased by a mean of 30% on discontinuation of PHT,
      with no change in CBZ-10, 11-epoxide (CBZ-E) concentrations; (c) VPA
      concentrations increased by a mean of 19% on discontinuation of PHT; (d) VPA
      concentrations increased by a mean of 42% on discontinuation of CBZ; (e)
      ethosuximide (ESM) concentrations increased by a mean of 48% on discontinuation
      of CBZ; (f) PHT concentrations decreased by a mean of 26% on discontinuation of
      CBZ; (g) PHT free fraction decreased from a mean of 0.11 to 0.07 on
      discontinuation of VPA; and (h) the mean concentrations of total and free CBZ
      increased by a mean of 10 and 16%, respectively, on VPA discontinuation, with a
      concomitant mean 24% decrease in total CBZ-E and a 22% decrease in free CBZ-E.
      Apart from the decrease in PB concentrations on PHT discontinuation, all
      significant changes had occurred by 1 week after the end of AED discontinuation.
      The implication for clinical practice is that a serum AED concentration at this
      time reflects the new steady state. Free concentrations did not add any
      clinically useful information to that gained from analysis of total serum
      concentrations.

PMID- 1985819
TI  - Cognitive function and time-of-day variation in serum carbamazepine concentration
      in epileptic patients treated with monotherapy.
AB  - Different parameters of antiepileptic drug (AED) treatment have been shown to
      affect cognitive function. The drug, dose, and duration of treatment have been
      studied. The present study assessed cognitive function in relation to time-of-day
      variation in serum carbamazepine (CBZ) concentration in epileptic patients
      treated with monotherapy. We studied 10 males and 12 females with a mean age of
      36 years and a mean duration of CBZ-therapy of 4.4 years. Patients had been
      seizure-free for at least 1 month and took two daily CBZ doses. The test battery
      included tests of motor speed, reaction time, attention, and memory. In the
      experimental design, the subjects were tested twice at times close to expected
      daily maximum and minimum serum CBZ concentration. They were studied in two
      balanced blocks (block 1 tested at 8 a.m. and noon, block 2 tested at noon and 8
      p.m.). Blood samples were collected every 2 hr from 8 a.m. to 8 p.m. The subjects
      showed significant differences in serum CBZ concentration between testing times,
      with suggested maximum concentration between 10 a.m. and noon. The test battery
      showed no consistent differences between performance at times of high versus low
      serum concentration. A supplementary analysis of correlations between mean
      performance level on cognitive tests and variables related to CBZ treatment did
      not show consistent trends.

PMID- 1985821
TI  - Carbamazepine-induced antinuclear antibodies and systemic lupus erythematosus
      like syndrome.
AB  - A 20-year-old woman developed a systemic lupus erythematosus (SLE)-like syndrome
      and a positive antinuclear antibody (ANA) soon after initiation of carbamazepine
      (CBZ) therapy. Symptoms and serology became normal after CBZ was discontinued.
      CBZ-induced SLE is an important but underecognized phenomenon.

PMID- 1985820
TI  - Immunologic aspects of carbamazepine treatment in epileptic patients.
AB  - Immune abnormalities have been found in epileptic patients receiving
      antiepileptic drugs (AEDs). Phenytoin (PHT) produces a decrease in serum IgA and
      IgM levels and a decrease in blastic transformation of circulating lymphocytes
      stimulated with phytohemoagglutinin (PHA). The effects of carbamazepine (CBZ) on
      the immune response are still conflicting. To elucidate the effects of CBZ on
      some immunologic parameters, serum concentrations of IgA, IgG, IgM, the
      phagocytosis and killing properties of polymorphonuclear leukocytes (PMNs), the
      cytotoxic activity of natural killer cells and the response of lymphocytes to
      mitogenic agents were studied. Forty healthy individuals and 39 epileptic
      patients treated with carbamazepine (CBZ) monotherapy (age range 18-40 years)
      entered the study. Student's t test was used to evaluate the data. CBZ had no
      effect on the serum immunoglobulin concentrations or on lymphocytic reactivity to
      phytohemoagglutinin (PHA) mitogen. CBZ produced a significant enhancement of
      phagocytosis and killing properties of PMNs and an increase in natural killer
      (NK) cell activity. Therefore, a negative effect of CBZ therapy on the immune
      system was not observed in this study.

PMID- 1985822
TI  - Effect of felbamate on plasma levels of carbamazepine and its metabolites.
AB  - Felbamate (FBM) is a novel antiepileptic drug (AED) currently undergoing clinical
      evaluation in the United States. During a controlled clinical trial conducted at
      the National Institutes of Health Clinical Center, FBM was added to constant
      carbamazepine (CBZ) monotherapy. CBZ total concentrations were reduced during
      active FBM treatment (mean reduction 25%, range 10-42%, p less than 0.001). The
      effect was evident after the first week of treatment and reached a plateau in 2-4
      weeks. To clarify the interaction mechanism, free and total concentrations of CBZ
      and its plasma metabolites were determined by high-performance liquid
      chromatography (HPLC) and ultrafiltration in four patients. In these patients,
      FBM treatment reduced CBZ concentrations and increased CBZ-epoxide (CBZ-E)
      concentrations (p less than 0.01). Free fractions of all compounds were
      unmodified. FBM appears to be capable of inducing CBZ metabolism. CBZ-FBM
      interaction may be clinically relevant.

PMID- 1985823
TI  - Double-blind, placebo-controlled, cross-over trial of progabide as add-on therapy
      in epileptic patients.
AB  - In a double-blind, cross-over trial, progabide (PGB) and placebo were compared as
      add-on therapy in 59 patients with moderate to severe epilepsy. Eight patients
      did not complete the study, 4 because of adverse drug reactions (elevation of
      liver transaminases, 2; gastritis, 1; and acute psychosis, 1) and 4 because of
      administrative reasons. Among the remaining 51 patients, seizure frequency was
      reduced greater than 50% in 18 patients with PGB treatment and in 8 patients with
      placebo (p less than 0.05). The number of days with seizures was significantly (p
      = 0.034) reduced during PGB treatment. Both patients' and physicians' preferences
      at the end of the trial were in favor (p less than 0.01) of PGB. Mild clinical
      side effects were present in 54.7% of the patients treated with PGB and in 37.7%
      with placebo. Increase in liver transaminases was observed in 2 patients during
      the double-blind study and in 1 during the follow-up period. Our data show that
      PGB, as previously reported, is useful in 30-40% of patients who are not
      responding completely to other antiepileptic drugs (AEDs). The compound is well
      tolerated, but liver function must be monitored.

PMID- 1985824
TI  - Development and reversal of contingent inefficacy and tolerance to the
      anticonvulsant effects of carbamazepine.
AB  - The relationship of the timing of drug administration to anticonvulsant efficacy
      against amygdala kindled seizures was studied. During kindling development, rats
      received carbamazepine (CBZ, 15mg/kg) before (CBZ-before) or after each amygdala
      stimulation (CBZ-after). After kindling to full seizures, when all animals were
      given CBZ before the stimulation, only the CBZ-after group showed a good
      anticonvulsant response. The rats that had received CBZ before (during
      development of kindled seizures) remained unresponsive to CBZ treatment
      (contingent inefficacy). When drug-naive or CBZ-after animals repeatedly received
      CBZ before electrical stimulation, they developed tolerance to its anticonvulsant
      effects (contingent tolerance). The tolerance could be reversed by a period of
      treatment with CBZ-after or by kindling the animal drug-free, but not by CBZ
      administration alone or by time off from both drug and seizures. These findings
      suggest that inefficacy and tolerance to CBZ may be affected by the temporal
      contingencies of drug administration and that responsiveness can be reinstated by
      altering these contingencies.

PMID- 1985825
TI  - Alterations in the renal excretion of valproate and its metabolites after chronic
      treatment.
AB  - Urinary excretion of valproate (VPA, administered as its sodium salt) and its
      various metabolites was studied in rats before and after 6 weeks of chronic
      treatment with intraperitoneal (i.p.) injection of 200 mg/kg VPA three times
      daily. Urinary excretion was determined after i.p. injection of a single dose of
      200 mg/kg VPA, to which [14C]labeled VPA had been added to yield a dose of 1
      microCi/kg body weight. Unlabeled VPA and metabolites were determined in urine by
      gas chromatography-mass spectrometry (GC-MS). After injection of a single dose of
      VPA before onset of chronic treatment, approximately 40-50% of the dose
      administered was excreted in the urine within 24 h, mainly in the form of
      conjugated VPA and omega-oxidation products, i.e., 5-hydroxy-VPA and 2-propyl
      glutaric acid. After chronic treatment, urinary excretion of total radioactivity
      increased approximately 75% as compared with activity before chronic treatment,
      demonstrating a marked increase in elimination rate of VPA during prolonged
      administration. Determination of VPA and metabolites in urine by GC-MS indicated
      that this enhanced elimination resulted mainly from increases in glucuronidation
      and beta-oxidation of VPA, whereas omega-oxidation was apparently not altered or
      was even reduced. The data strongly indicate that at least in rats VPA produces
      induction of its own metabolism during prolonged treatment.

PMID- 1985826
TI  - Kindling susceptibility and genetic seizure predisposition in inbred mice.
AB  - Olfactory bulb kindling rates were studied in two inbred strains of genetically
      seizure-prone mice (DBA/2 and El) and in three non-epileptic inbred strains
      [C57BL/6 (B6), ddY, and C3H/He (C3H)]. None of the DBA/2 mice had been stimulated
      to seizure before or during the kindling and all mice were studied at 4-6 weeks
      of age, before development of spontaneous or movement-induced seizure activity in
      the El strain. The audiogenically seizure-susceptible DBA/2 mice required the
      fewest number of stimulations to reach stage 5 seizure (mean +/- SE = 4.0 +/-
      0.6). The nonepileptic C3H mice required the most stimulations to reach stage 5
      seizures (22.6 +/- 1.4). Kindling rates for B6 (9.6 +/- 0.6), El (14.8 +/- 1.1),
      and ddY (18.5 +/- 1.0) strains were intermediate, and the kindling rate for each
      strain was significantly different from that of the other strains. These findings
      show that the seizure-susceptible El mouse kindles more rapidly than the
      genetically similar but nonepileptic ddY control and suggest that an inherited
      seizure susceptibility accelerates the kindling rate. Nonepileptic B6 mice
      kindled more rapidly than El mice, however, suggesting that genetic factors other
      than those that influence seizure susceptibility are of primary importance in the
      determination of the kindling rate.

PMID- 1985827
TI  - Changes of hippocampal glucose utilization subsequent to amygdaloid-kindled
      generalized seizures.
AB  - Local changes in cerebral glucose utilization during the postictal phase of
      amygdaloid-kindled generalized seizures were studied with the quantitative
      autoradiographic 2-[14C]deoxyglucose method in conscious rats. Measurement was
      initiated either just after termination of a behavioral seizure (GS-I) or 30 s
      after seizure termination (GS-II) to determine dynamic metabolic changes in the
      postictal phase. Although glucose utilization of the neocortex was remarkably
      depressed in both GS-I and GS-II, that of the hippocampus significantly increased
      in GS-I and then decreased in GS-II as compared with control. These changes of
      hippocampal glucose utilization were observed in all sectors of the pyramidal
      cell layer (CA 1-4) and in the molecular layer. Because metabolic changes
      associated with development of amygdaloid-kindled seizures begin in the limbic
      structures including the hippocampus, the transient increase in hippocampal
      glucose utilization observed in the early postictal phase indicates that the
      hippocampus is one of the key structures not only for initiating and maintaining
      but also for terminating kindled seizures.

PMID- 1985828
TI  - Panic disorder in seizure patients: a diagnostic pitfall.
AB  - Panic disorder is a psychiatric diagnosis whose main feature is paroxysmal
      attacks of anxiety that strike suddenly without apparent provocation. Physicians
      explain the attacks as an ictal phenomenon in patients with known seizures
      because of their similarities to complex partial seizures. We report eight
      patients with seizures and panic disorder. Recognition of a second diagnostic
      entity resulted in a beneficial change in treatment in six of the eight. We did
      not find an increased incidence of panic disorder in our seizure clinic
      population as compared with the general population.

PMID- 1985829
TI  - Effect of epilepsy and sleep deprivation on the rate of benign epileptiform
      transients of sleep.
AB  - Seventy-eight individuals with EEG records containing benign epileptiform
      transients of sleep (BETS) were identified among 7,400 records reviewed in our
      laboratory in a 6-year period. The records contained no other abnormality in 51
      patients (65%). Genuine epileptiform discharges were found in the records of 19
      patients; 14 had a history of epilepsy. Thirty-five patients (45%) had a proven
      history of epilepsy with antiepileptic drug (AED) therapy. In the records of
      these patients, the mean number of BETS per unit of time was significantly higher
      (11.88 +/- 2) than in the record of the rest of the laboratory population with
      BETS (6.89 +/- 0.9) (p less than 0.02). Among five conventional surface montages,
      ipsilateral ear referential montage (IERM) showed a significantly higher number
      of BETS per unit of time than did any other surface montage used in the study.
      Thirty-nine records (50%) were performed after sleep deprivation (SD). When only
      IERM was considered, SD records showed a significantly higher number of BETS per
      unit of time (7.36 +/- 1.1) than did non-SD records (3.89 +/- 0.69) (p less than
      0.01). Our findings support the general consensus that individual BETS may be
      normal variants, but a high occurrence of BETS in the record should raise
      suspicion of underlying epilepsy.

PMID- 1985830
TI  - Dreams and epilepsy.
AB  - The relationship between dreams and epilepsy is illustrated by two patients whose
      awake epileptic seizures and recurrent dreams during night sleep had similar
      content. In both of our cases the EEG showed right anterior temporal spike
      discharge, suggesting a role for the temporal lobe in the association between
      dreams and seizures.

PMID- 1985831
TI  - Epilepsy with continuous spike-waves during slow sleep and its treatment.
AB  - Five children with epilepsy with "continuous spike-waves during slow sleep"
      (CSWS) are reported. The main clinical features of CSWS include (a) onset between
      5 and 7 years of age, (b) the occurrence of several types of seizure (i.e.,
      partial motor, generalized motor, and atypical absence), and (c) the presence of
      language disturbances and abnormal behavior based on emotional impairment. The
      EEG findings were characterized by sleep tracings showing almost continuous
      (greater than 95%), diffuse slow spike and wave activity. After treatment with
      valproate (VPA) (or ethosuximide, ESM) and clonazepam (CZP), the spike and wave
      complex status disappeared. Symptoms and signs of the CSWS also decreased. We
      suggest that combined treatment is an appropriate treatment for CSWS.

PMID- 1985832
TI  - Postnatal epilepsy after EEG-confirmed neonatal seizures.
AB  - We examined infants whose neonatal seizures were confirmed by randomly recorded
      ictal EEG tracings to determine the types and frequency of postnatal epilepsy
      (PNE)--unprovoked, recurring postnatal seizures. Perinatal and postnatal clinical
      and EEG variables were also examined for their relevance to PNE. Forty infants
      with EEG-documented neonatal seizures of diverse etiologies were studied. The 27
      survivors were followed for a mean of 31 months. PNE developed in 56% (15 of 27)
      of the cohort. The first seizure appeared at a mean-corrected age of 12.7 months
      and occurred despite ongoing antiepileptic medication in 60% (9 of 15) of the
      group. Seizures were classified as infantile spasms or minor motor (7 patients),
      complex partial (4 patients), or generalized tonic-clonic (4 patients). Perinatal
      variables that significantly correlated with PNE included the presence of coma
      but not the age at seizure onset, the estimated gestational age, or Apgar scores.
      PNE occurred in 68% (13 of 19) of patients with moderately or markedly abnormal
      EEG backgrounds but in only 25% (2 of 8) without (p = 0.035). There was a strong
      trend for PNE to develop in patients with greater than 10 electrographic seizures
      per hour but in only 45% (9 of 20) of infants with fewer seizures (p = 0.058).
      Several postnatal variables were significantly related to PNE--the presence of
      cerebral palsy (CP), mental retardation (MR), CP with MR, and follow-up EEGs. PNE
      occurred in only 27% (3 of 11) of patients without spikes or sharp waves on
      postnatal EEGs performed at age 3 months but in 100% (3 of 3) of patients with
      spikes or sharp waves (p = 0.022).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1985833
TI  - Photosensitive epilepsies and photoconvulsive responses in Arabs.
AB  - The occurrence of photosensitivity (PS) was examined in 327 Arabs greater than or
      equal to 15 years of age with epilepsy by intermittent photic stimulation (IPS).
      A control group of 192 nonepileptic Arabs greater than or equal to 15 years of
      age were also examined by IPS. Of the epileptic patients, 24 (7.3%) were
      photosensitive, an incidence comparable to that in whites in contradistinction to
      the reported rarity among African blacks. This finding indicates that
      environmental factors, particularly excessive sunshine, does not appear to
      influence the occurrence of PS among epileptic patients. The occurrence of PS
      among epileptic patients may depend more strongly on the presence of an epileptic
      syndrome known to have association with PS.

PMID- 1985834
TI  - Sexual behavior of a sample of females with epilepsy.
AB  - A sample of 700 female epileptic outpatients was examined between 1985 and 1987.
      The incidence of psychosexual disorders was 18%. Epileptic females with
      psychosexual disorders were compared with epileptic females without sexual
      disorders and with normal female controls on selected clinical and EEG
      parameters. Epileptic females with sexual disorders showed: lower marriage rates,
      a longer duration of illness, sexually colored prodromata, predominance of
      partial complex seizures (83%) and a higher incidence of menstrual abnormalities.
      Hyposexuality and exhibitionism were the psychosexual disorders most frequently
      noted. Temporal lobe EEG abnormalities were significantly higher.

PMID- 1985835
TI  - Attitudes of major employers toward the employment of people with epilepsy: a 30
      year study.
AB  - Beginning in 1956, major San Francisco Bay area employers were sampled at 10-year
      intervals for a 30-year period to assess attitudes toward the employment of
      epileptic workers. In this time, we documented a trend of sustained positive
      change that appears to validate the efforts of organizations that have focused on
      raising public awareness of this disorder.

PMID- 1985836
TI  - Antiepileptic drug monitoring at the epilepsy clinic: a prospective evaluation.
AB  - To assess the value of on site therapeutic drug monitoring at the epilepsy
      clinic, management decisions were recorded before and immediately after
      antiepileptic drug (AED) concentrations became available. In the first year of
      this prospective study, 632 [277 carbamazepine (CBZ), 170 phenytoin (PHT), 113
      valproate (VPA), and 72 phenobarbital (PB)] assays were performed during 488
      clinic attendances in 182 actively managed epileptic patients. The results of
      drug analysis led to alterations in management at 114 patients visits, i.e., 23%
      of those monitored. Dosage was increased in response to the circulating AED
      concentration in 12% of consultations and decreased in another 7.5%. Unsuspected
      poor compliance was uncovered in eight patients, and in three others an AED was
      added or discontinued on the basis of the assay result. The time of the next
      appointment was rearranged in 58 attendances. Only 50% of results were in the
      "therapeutic" ranges for the four major AEDs. Dosage was adjusted (50 up, 16
      down) after 54% of low results. "Therapeutic" levels were followed by a change in
      AED dose (52 up, 31 down) in 26%. Only 29% of concentrations above the
      "therapeutic" range persuaded the doctor to alter the dosage regimen, and in 20%
      of these an increase in dose was recommended. On-site AED monitoring had an
      immediate impact on clinical decision-making in greater than 23% of consultations
      but in a form more subtle than the simple quest for a therapeutic result.

PMID- 1985837
TI  - Antiepileptic drug intoxication: factors and their significance.
AB  - A retrospective chart review (1979-1985) was performed to identify probable
      causes of intoxication with antiepileptic drugs (AEDs). We identified 141
      patients meeting clinical and laboratory criteria for intoxication and 17 with
      clinical signs but with serum concentrations within the therapeutic range. The
      majority were epileptic patients; almost half were treated with monotherapy, most
      with phenytoin (PHT). The causes of intoxication in the epileptic patients were
      iatrogenic (41%), inappropriate dose self-adjustment (34%), suicide attempt
      (18%), inappropriate caretaker dose adjustment (9%), accidental ingestion (8%),
      unrecognized drug interaction (6%), and association with intercurrent illness
      (2%). Twenty-two patients had more than one probable cause of intoxication. In
      nonepileptic patients the causes were suicide attempt (50%), accidental ingestion
      (27%), and iatrogenic (23%). Most patients had signs of ocularmotor and
      vestibulocerebellar dysfunction. Rarely described manifestations of intoxication,
      such as seizures or choreoathethosis, were observed in a few patients. The
      average hospital stay was 6.9 days; there was no mortality, and all patients
      recovered fully. We conclude that AED intoxication is a major but preventable
      cause of morbidity and that suicide attempts are an important and underrecognized
      contributor in both epileptic and non-epileptic patients.

PMID- 1985838
TI  - Third quarter HAS/Monitrend II data from AHA.

PMID- 1985839
TI  - Congressional leaders outline their health agendas. Interview by Marybeth Burke.

PMID- 1985841
TI  - New budget rules hold uncertainty for Medicare.

PMID- 1985840
TI  - Local governments call for health care reform.

PMID- 1985842
TI  - Home health, diagnostic centers were financial winners in 1990.
AB  - The importance of outpatient services to hospitals' total net patients revenues
      continues to increase steadily. In fact, nearly one-third of those participating
      in our fourth annual survey on diversification gauged outpatient services as
      providing 30 percent or more of their total net patient revenues in 1990.

PMID- 1985843
TI  - Survey: non-Medicare home care a financial winner for hospitals.

PMID- 1985844
TI  - New JCAHO report assesses hospitals' standards compliance.
AB  - The JCAHO recently released a report detailing hospitals' compliance with
      accreditation standards. What's behind the varying levels of compliance? The
      JCAHO is finding a mixed picture: generally partial compliance, with small and
      rural hospitals struggling to keep up with mandated standards.

PMID- 1985845
TI  - The AHA's priorities for 1991.
AB  - The next decade presents formidable challenges for hospitals and for American
      health care in general. Whatever emerges from the current health care reform
      debates, a fundamental shift is taking place toward outpatient and non-hospital
      site care. Carol M. McCarthy, J.D., Ph.D, AHA president, outlines the
      association's plans for the coming year.

PMID- 1985846
TI  - Sleep disorder centers: how to plan a successful program.

PMID- 1985847
TI  - 25 warning signs of quality problems.

PMID- 1985848
TI  - Hospitals gain from Oregon plan, says Medicaid director.

PMID- 1985849
TI  - Early warning signs predict financial trouble.

PMID- 1985850
TI  - Gainsharing gives employees rewards for innovation.

PMID- 1985851
TI  - Post-payment UR yields big savings for PA Blue Shield.

PMID- 1985852
TI  - OBRA's on-call requirement may cause MD backlash.

PMID- 1985853
TI  - 'Authentic' organization emerges as fear fades.

PMID- 1985854
TI  - Little payer interest in quality data--for now.

PMID- 1985855
TI  - 'Adhocracy': lessons from the changemasters.

PMID- 1985856
TI  - Hospitals with the best information systems. 1991 SDR awards of excellence.
AB  - For the second year, 12 hospitals with truly exceptional information systems are
      highlighted in Hospitals. The Shared Data Research Second Annual Award of
      Excellence is presented to those institutions showing leadership in information
      systems management. Recognition is based on cost and performance factors. As
      investment in these systems grows, so does executives' interest in measuring
      their cost and performance. Indeed, U.S. hospitals spent more than $6.5 billion
      on materials services in this area in 1989. "Hospitals with the Best Information
      Systems" leads off our 14-page Factbook--a guide to the 1991 HIMSS Annual
      Conference, to be held Feb. 11-14 in San Francisco.

PMID- 1985857
TI  - Data watch. What consumers want in an ob/gyn specialist.

PMID- 1985858
TI  - The class of 1970: making connections with change.
AB  - Whatever happened to the class of 1970? For the most part, they're still right
      here in our midst. But a lot has changed since the young people (mostly young
      men) who took their MHAs from health administration programs left school.
      Although many started out with their eye on the hospital CEO prize, the 1970
      grads have fanned out across the health care profession spectrum--and beyond. The
      kinds of changes in the health care field the 1970 MHA graduates have seen are
      the ones that have transformed health care in just two decades. PPS, managed
      care, the indigent care crisis, downsizing, the growth of systems, greater
      physician scrutiny and an avalanche of regulations of all types have
      fundamentally altered the health care career map. The 1970 grads will tell you-
      in their own words--what two decades of revolution have meant to them--and to all
      of us.

PMID- 1985859
TI  - Conflicting hospital performance data: who's right?
AB  - Take your pick. The hospital field's financial performance for 1989 was either:
      (a) bad; or (b) worse. The answer depends on whose performance report you're
      looking at. Three recently released reports by Van Kampen Merritt Investment
      Advisory Group, Health Care Investment Analysts Inc. and the Healthcare Financial
      Management Association disagree on just how bad hospitals' financial picture
      really is--although all agree that the situation is bleak at best.

PMID- 1985860
TI  - Survey: pulmonologists generate highest revenues for hospitals.
AB  - Although obstetricians and gynecologists admitted the most patients to hospitals
      in 1989, pulmonologists generated the highest revenues for hospitals. The fifth
      annual Physician Revenues Survey, which was conducted by Jackson & Coker and the
      Atlanta office of Ernst & Young, has found some intriguing results among the 800
      plus hospitals polled. Only Hospitals gives you detailed, regional survey data.

PMID- 1985861
TI  - Mammography demand continues strong growth.

PMID- 1985862
TI  - Pete Stark: 'consumerist' or curmudgeon?
AB  - What do hospital CEOs think of Congressman Pete Stark? The California legislator
      has used his post as chair of the powerful House Ways and Means Health
      Subcommittee to attack what he sees as fraud and abuse in the health care system.
      Not surprisingly, many see Stark's campaigns in a negative light.

PMID- 1985863
TI  - CEOs begin to share control of IS purchases.
AB  - Although senior executives and departmental staff frequently play a role in
      information management purchasing decisions, chief executives still have
      accountability for final decision making--especially when the purchases involved
      are capital-intensive. However, according to an exclusive survey of executives
      conducted by Hospitals, things are slowly beginning to change.

PMID- 1985864
TI  - Whose voice should be heard by Congress?

PMID- 1985865
TI  - Meta-iodobenzylguanidine (mIBG) uptake and storage in the human neuroblastoma
      cell line SK-N-BE(2C).
AB  - Whilst many human neuroblastoma cell lines have been studied to see if they are
      capable of taking up mIBG, few appear to have this ability. This contrasts
      markedly to the situation in vivo, where uptake has been demonstrated in the
      majority of tumours investigated. Here we report on the human neuroblastoma cell
      line SK-N-BE(2C) and demonstrate that mIBG uptake can occur in this cell line
      through 2 mechanisms. At low concentrations of mIBG (approximately 10(-8) M) an
      active transport process predominates, whereas at non-physiological levels (10(
      4) M) uptake occurs through passive diffusion. The active transport process is
      ATP-, Na(+)- and temperature-dependent. Uptake is blocked by 10(-6) M
      desipramine, an inhibitor of the uptake-I mechanism involved in amine transport.
      In contrast, desipramine has no effect on the passive diffusion of mIBG into
      cells. The active transport mechanism for mIBG uptake appears rather promiscuous
      for biogenic amines, as dopamine, tyramine and nor-adrenaline were highly
      efficient at blocking mIBG entry to the cell. Serotonin and histamine were
      capable of interfering with mIBG uptake only at much higher concentrations.
      Electron microscopy of SK-N-BE(2C) cells revealed a paucity of neurosecretory
      granules. Biochemical investigations demonstrated the majority of mIBG to be
      present in the cytoplasm of cells. The availability of a human neuroblastoma cell
      line that grows well, both as xenograft and in culture, should further our
      understanding of the cytotoxic effects of mIBG and thus enhance its clinical
      usefulness.

PMID- 1985866
TI  - Dominance of metastatically competent cells in primary murine breast neoplasms is
      necessary for distant metastatic spread.
AB  - We have previously shown, using tumor cell populations genetically tagged by
      random integrations of plasmid DNA, that metastatically-competent clonal cell
      variants have a strong growth advantage within primary tumors over their non
      metastatic counterparts. As a result, primary tumors can become overgrown by the
      progeny of such cells, a process referred to as "clonal dominance" of primary
      tumors by metastatically-competent cells. Because of the well-known "metastatic
      inefficiency" of the multi-step cascade process of spread and growth, clonal
      dominance within primary tumors may be necessary for distant metastatic spread or
      increase the probability of its occurrence. To examine this hypothesis mice were
      inoculated s.c. with mixture of non-metastatic and genetically tagged,
      metastatically-competent mouse mammary carcinoma cells in defined ratios, but
      always containing an excess of the unmarked non-metastatic population.
      Progressive overgrowth of the metastatic subpopulation was monitored as a
      function of time by Southern analysis of DNA obtained from mixed primary tumors.
      This allowed us to evaluate the effects that surgical removal of the primary
      tumor had before, during and after effective clonal dominance, and what influence
      this had on the subsequent formation of distant metastases. Surgical removal of
      primary tumors before metastatic clonal dominance resulted in a low (0.25%)
      frequency of lung metastases, whereas removal just 1 or 2 weeks later during or
      after clonal dominance was achieved resulted in a high (75-100%) frequency of
      such metastases. Our results support the hypothesis that dominance of primary
      tumors by metastatically competent cells may be necessary for distant metastatic
      spread, and also suggest that clonal interactions play a significant role in
      modulating the metastatic ability of tumor cells in vivo.

PMID- 1985867
TI  - The Nordic profile of skin cancer incidence. A comparative epidemiological study
      of the three main types of skin cancer.
AB  - The data used for the inter-Nordic comparison of the incidence of skin cancer are
      based on the material of the national cancer registries of the 5 Nordic
      countries. It is typical of these countries that the ratio between the incidence
      of non-melanoma and melanoma skin cancer is much smaller than in regions near the
      Equator. For the detailed comparative epidemiological study of basal-cell
      carcinoma (BCC), squamous-cell carcinoma (SCC) and cutaneous malignant melanoma
      (CMM), the material from the Norwegian Cancer Registry 1955-1988 is used. The
      etiology of CMM has frequently been debated during recent decades. There are
      still some obscure points, however, particularly as regards the influence of host
      factors and UV exposure, and their interaction. The analysis of the incidence
      trend of CMM on the female breast during the time interval 1970-1988 contributes
      to the elucidation of these problems. Differences in the epidemiological
      characteristics of the 2 main types of non-melanoma skin cancer, BCC and SCC, are
      described. The results indicate that the effect of UV light is not a dominating
      for BCC as for SCC.

PMID- 1985868
TI  - Characterization of NCAM expression and function in BT4C and BT4Cn glioma cells.
AB  - The neural cell adhesion molecule, NCAM, plays an important role in cell-cell
      adhesion. Therefore, we have studied NCAM expression in the glioma cell lines
      BT4C and BT4Cn. We demonstrate that the 2 cell lines differ in their metastatic
      ability; while BT4C cells have a very low capacity for producing experimental
      metastases, that of BT4Cn cells is high. In BT4C cells NCAM is synthesized as 4
      polypeptides with Mr's of 190,000, 140,000, 115,000 and 97,000. The 140,000,
      115,000 and 97,000 polypeptides are glycosylated and for the 140,000 and 115,000
      polypeptides sulfatation is observed. Conversely, no NCAM protein synthesis is
      observed in BT4Cn cells, even though NCAM mRNA is expressed. Thus, development of
      an increased metastatic capacity is accompanied by the disappearance of NCAM
      protein expression in this model system. The functional importance of NCAM
      expression was studied by a cell-substratum binding assay in which the binding of
      BT4C and BT4Cn cells to NCAM immobilized to glass was assessed. We found that
      BT4C cells adhere specifically to NCAM, and that adhesion is inhibited by anti
      NCAM Fab'-fragments, while no specific binding of BT4Cn cells to NCAM was
      observed. The BT4C and BT4Cn cell lines thus constitute an important new model
      system for the study of tumor invasion and metastasis and of the role of cell
      adhesion molecules in these processes.

PMID- 1985869
TI  - Comparative biochemical, cytotoxic and pharmacokinetic properties of immunotoxins
      made with native ricin A chain, ricin A1 chain and recombinant ricin A chain.
AB  - Immunotoxins were constructed by attaching native ricin A chain, ricin A1 chain
      and recombinant ricin A chain to the mouse monoclonal IgG2a antibody Fib75 by
      means of a disulphide linkage using the hetero-bifunctional cross-linker SPDP.
      The Fib75 immunotoxins were of similar composition and exerted identical
      cytotoxic effects against the EJ human bladder carcinoma cell line in tissue
      culture. All 3 immunotoxins broke down to the same extent upon incubation with
      glutathione in vitro. The clearance of the immunotoxins from the circulation of
      normal Wistar rats was determined following i.v. administration. The
      concentration of intact immunotoxin in serum samples taken at various intervals
      up to 48hr after injection was measured by a ricin A chain-specific ELISA. The
      Fib75 immunotoxin made with native ricin A chain was removed from the circulation
      most rapidly. Fib75-recombinant ricin A chain persisted in the circulation at a
      higher level than Fib75-ricin A1 chain. A higher proportion of the ricin A1 chain
      immunotoxin was lost from the bloodstream during the alpha-phase. The beta-phase
      half-lives of Fib75-recombinant ricin A chain and Fib75-ricin A1 chain were
      similar, consistent with the identical susceptibility of the immunotoxins to
      cleavage by glutathione. The presence of the complex-type oligosaccharide side
      chain on the A1 chain may have accelerated the clearance of the A1 chain
      immunotoxin in relation to that of the immunotoxin made with the aglycosyl
      recombinant A chain.

PMID- 1985870
TI  - Anti-tumor effects of recombinant human macrophage colony-stimulating factor,
      alone or in combination with local irradiation, in mice inoculated with Lewis
      lung carcinoma cells.
AB  - Recombinant human (rhu) macrophage colony-stimulating factor (M-CSF) was
      evaluated for efficacy, either alone or in combination with local X-irradiation
      (LR), in mice inoculated subcutaneously (s.c.) with Lewis lung carcinoma (LLC)
      cells. The size of the primary tumor and numbers of lung metastases, 21 days
      after tumor inoculation and 15 days after the start of treatment, were reduced by
      87% in tumor-bearing mice treated with 20 micrograms/dose M-CSF s.c. twice a day
      for 5 days. LR (800 cGy) to the tumor once a week for 2 weeks had a moderate anti
      tumor effect and enhanced the anti-tumor effect of M-CSF. Hematological
      parameters, including nucleated cellularity in peripheral blood, femoral marrow,
      spleen and peritoneal exudate, as well as marrow and splenic granulocyte
      macrophage progenitor cells, and numbers of splenic Thy 1.2+ cell and peritoneal
      mast cells, were perturbed in LLC-bearing mice, and were influenced by treatment
      with M-CSF and LR. Treatment with M-CSF plus LR, but not with either agent alone,
      was associated with a significant, although slight, enhancement in survival time
      for LLC-bearing mice. Inability to obtain a better survival-enhancing effect
      appeared to be related to the limited treatment, since the anti-tumor effects of
      M-CSF were more notable early on in disease progression and were related to the
      dose of M-CSF used. The effects of M-CSF were most probably indirect ones on the
      host immune system. M-CSF, in combination with LR, may be of benefit in the
      treatment of human tumors that have metastatic potential.

PMID- 1985871
TI  - Suppression of established pulmonary metastases by murine melanoma-specific
      monoclonal antibodies.
AB  - The intravenous administration of melanoma-specific monoclonal antibodies (MAbs)
      9B6 and T97, both of the IgG2b isotype, consistently suppressed the growth of
      established JB/MS murine melanoma lung metastases. This activity was not dose
      dependent, lower doses of MAbs often being more suppressive than higher doses.
      Intravenous administration of antibodies at days 5 and 8 following challenge
      appeared to be optimal for suppression whereas no inhibition was seen with
      intravenous treatment at days 0 and 3 or at days 10 and 13. Consistent and
      significant inhibition was also observed using established B16F10 lung metastases
      but only at lower doses, whereas both MAbs were ineffective against the T92497
      sarcoma in syngeneic mice. These MAbs appear to act not as direct anti-tumor
      agents but as host immune response regulators, since specific anti-tumor effects
      were abrogated in tumor-bearing hosts following pre-treatment with antibodies
      directed against asialo-GM1 and NK-1.1, surface markers of natural killer cells.

PMID- 1985872
TI  - Loss of Y chromosome with retention of Y heterochromatin in a marker chromosome
      from a human melanoma.
AB  - A single copy of a der 15 chromosome (m3) characterized by a C- and distamycin A
      Dapi-positive region was observed in the -Y hyperploid karyotype of a primary
      human melanoma (Me 1402). The heterochromatic region was located
      pericentromerically, adjacent at one end to the NOR region of chromosome 15, and
      at the other to an unclassifiable chromosomal piece. We established that the C
      positive block in the marker chromosome originated from Y heterochromatin by high
      stringency in situ hybridization with a DNA probe for the 2.1 Hae III Y-specific
      repeat. Loss of the Y chromosome in tumors has been considered to be a secondary
      event associated with malignant evolution. It is significant that Me 1402 cells,
      which are highly malignant, lack the Y chromosome, but retain its heterochromatic
      portion in the rearranged m3 chromosome.

PMID- 1985873
TI  - Antibodies to HTLV-I among blood donors in Latvia, USSR.

PMID- 1985874
TI  - Nutrition and cancer of the oral cavity and pharynx in north-east Italy.
AB  - The relation between dietary indicators and the risk of cancer of the oral cavity
      and pharynx was investigated in a case-control study conducted in Pordenone
      province, north-east Italy, on 302 cases (266 males and 36 females) and 699
      controls admitted to hospital for acute, non-neoplastic and non-digestive
      disorders. Positive associations were observed, after allowing for occupation,
      smoking and drinking habits, with more frequent consumption of pasta or rice,
      polenta, cheese, eggs and pulses (odds ratios - ORs = 1.6, 2.1, 1.9, 1.9 and 2.0
      for highest vs. lowest tertile), whereas reduced ORs emerged in subjects
      reporting more frequent consumption of carrots, fresh tomatoes and green peppers
      (ORs = 0.6, 0.5 and 0.5, respectively). Higher frequency of daily meals was also
      associated with a significantly elevated OR (1.7 for greater than or equal to 4
      vs. less than or equal to 2 meals). The role of various indicator foods must be
      assessed in the context of the very high levels of alcohol consumption in the
      study area (greater than or equal to 8 alcoholic drinks/day in 2/3 cancer cases).

PMID- 1985875
TI  - Prognostic importance of cellular DNA content in head-and-neck squamous-cell
      cancers. A comparison of retrospective and prospective series.
AB  - Flow cytometric DNA-ploidy measurements were performed on formalin-fixed tumour
      specimens from 172 patients with squamous-cell cancers (SCCs) of the head and
      neck region. One hundred and two samples were chosen retrospectively and a
      further 70 consecutive patients were analysed prospectively in order to assess
      the prognostic significance of DNA ploidy and DNA index (DI). There were no
      statistically significant differences between retrospective and prospective
      groups in regard to age, sex, TNM stage, ploidy or DI. Sixty-seven percent of
      patients were aneuploid (65% retrospective; 71% prospective). The proportion of
      aneuploid tumours was significantly higher among poorly differentiated tumours.
      Survival analysis using Cox multivariate regression modelling revealed that DNA
      aneuploidy and increasing DI were significant independent prognostic factors for
      both relapse-free and overall survival. The relapse and death rates among
      aneuploid subjects were approximately 3 times as high as those for diploid
      subjects. Patients with a DI greater than 2.11 (hypertetraploidy) experienced a
      6.6-fold higher death rate than diploid subjects. These results provide strong
      support for the incorporation of DNA ploidy profiles into the clinical management
      of patients with head and neck cancer.

PMID- 1985876
TI  - Diffuse centrocytic and/or centroblastic malignant non-Hodgkin's lymphomas:
      comparison of mitotic and pyknotic (apoptotic) indices.
AB  - Mitotic indices (MIs) and pyknotic (apoptotic) indices (PIs) were assessed in
      diffuse centrocytic (CC, n = 10), centroblastic/centrocytic (CB/CC, n = 18) and
      centroblastic (CB, n = 20) malignant non-Hodgkin's lymphomas (NHL). Significant
      differences were observed. MIs were lowest in CC (median: 0.07%), intermediate in
      CB/CC (0.18%) and highest in CB (0.43%) NHLs. The PIs exhibited a similar
      pattern. The PIs of CC (0.11%) and CB/CC (0.17%) NHLs were significantly
      different from those of CB lymphoma (0.62%). The ratios MI/PI per case, as well
      as MIs and PIs per case, varied greatly and showed considerable overlapping, thus
      documenting a marked inter-case and inter-group heterogeneity. MIs tended to
      loosely correlate with PIs in a non-linear fashion, which raises the question of
      feedback mechanisms. More information is needed on mitotic time (TM) and
      apoptotic time (TA), in order to estimate cell doubling time from data on MIs and
      PIs.

PMID- 1985877
TI  - Differential sensitivity of various human tumors to inhibition of polyamine
      biosynthesis in vivo.
AB  - Polyamines are essential for normal and neoplastic growth. Ornithine
      decarboxylase (ODC) is the first and rate-limiting enzyme in the polyamine
      biosynthetic pathway. alpha-Difluoromethylornithine (DFMO) is an enzyme-activated
      irreversible inhibitor of ODC, and a known anti-neoplastic agent. The purpose of
      this study was to examine the susceptibility of various human cancers to
      inhibition by DFMO in vivo. We have studied three human pancreatic
      adenocarcinomas, designated CAV, SKI, and PGER, two human colon adenocarcinomas
      (LS-180 and WIDR), and three metastatic cell lines of a human gastric
      adenocarcinoma (BHM, BMM, BLM) that were growing in congenitally athymic (nude)
      Balb/c mice. Mice bearing each tumor were divided into two groups; one group
      served as controls and the other group received DFMO 3% in drinking water. Tumor
      growth and weight, and content of DNA, RNA, protein and polyamines were
      determined and correlated. DFMO significantly inhibited the growth of three of
      the three gastric tumors, two of the three pancreatic tumors and neither of the
      two colon tumors. The tumor content of DNA, RNA and protein exhibited a pattern
      that was parallel to tumor growth. The tumor polyamine concentration did not
      correlate with sensitivity to DFMO. These findings provide clear evidence for
      important differences in the sensitivity of various human cancers to growth
      inhibition by DFMO and indicate that endogenous polyamine levels alone do not
      predict the sensitivity of the tumors to DFMO.

PMID- 1985878
TI  - Kaposi's sarcoma and non-Hodgkin's lymphoma in European AIDS cases. No excess
      risk of Kaposi's sarcoma in Mediterranean countries.
AB  - Prior to the AIDS epidemic, Kaposi's sarcoma (non-AIDS-KS) in Europe was mainly a
      disease of elderly Mediterranean men. In 1989 AIDS data from 15 European
      countries were collected to study proportional trends in AIDS-related Kaposi's
      sarcoma (AIDS-KS) in order to determine whether specific factors in Southern
      Europe might be important in the development of KS among AIDS patients. Another
      AIDS-related cancer, non-Hodgkin's lymphoma (NHL) was included as a malignancy
      control. Of 22,367 AIDS cases reported, 3,779 (16.9%) were KS and 741 (3.3%) were
      NHL. A significant, continuous fall in the percentage of AIDS-KS was seen for
      both homosexual men and other members of exposure groups during the period 1981
      89 (p-trend less than 0.0001). The proportion with AIDS-KS decreased from 40.5%
      in 1983 to 26.5% in 1988 in homosexual men and from 12.2 to 3.6% in other
      exposure groups, respectively. No significant change was observed in the
      proportion of NHL cases among any of the risk groups over time, although a
      tendency towards a slight increase was noted for homosexual men. Comparing
      proportional trends of KS and NHL geographically, no significant difference was
      found overall, by time or by exposure group. In conclusion, a specific decline is
      observed over time for AIDS-KS. However, if geographically-restricted factors are
      important in the development of non-AIDS-KS in Europe, the same factors do not
      appear to affect the risk of AIDS-KS.

PMID- 1985879
TI  - Enhancement by sulpiride of the inhibitory effects of cysteamine on gastric
      carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.
AB  - The effects of sulpiride on cysteamine inhibition of gastric carcinogenesis
      induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and on the BUdR labelling
      index of gastric mucosa were investigated in inbred Wistar rats. After 25 weeks
      of oral treatment with MNNG, rats received one of the following alternate-day
      injections: cysteamine (2 doses), cysteamine (2 doses) plus sulpiride or
      sulpiride. At week 52, prolonged administration of cysteamine significantly
      reduced the incidence of adenocarcinomas of the glandular stomach. Cysteamine at
      low dose had no effect on the incidence of gastric cancers, but a combination of
      low-dose cysteamine and sulpiride caused a significantly greater reduction in the
      incidence of gastric cancers. Administration of sulpiride alone had no influence
      on gastric carcinogenesis. The labelling index of the antral mucosa was
      significantly lower in rats treated with high but not low doses of cysteamine.
      However, a combination of low-dose cysteamine and sulpiride significantly
      decreased the labelling index of the antral mucosa. Our findings indicate that
      cysteamine suppressed gastric carcinogenesis and that sulpiride enhanced this
      inhibition. Because sulpiride is a dopamine antagonist, these findings also
      indicate that dopamine may play an important role in cysteamine inhibition of
      gastric carcinogenesis.

PMID- 1985880
TI  - Role of activated c-H-ras oncogene in the induction and progression of immortal
      liver epithelial cell lines derived from normal C3H mice.
AB  - The nature of 15 immortal mouse liver epithelial cell (MLEC) lines established
      from normal C3H mice was investigated specifically in terms of ras oncogene
      activation. Neither transforming activity nor point mutation within codon 61 of c
      H-ras could be demonstrated in any of the cell lines by DNA transfection in a
      NIH/3T3 cell system or by the direct sequencing method after polymerase chain
      reaction, respectively. Acrylamide gel migration analysis of ras p21 products did
      not show any shift from the normal. Transplantation experiments demonstrated only
      2 out of the 15 lines to be tumorigenic in nude mice. When 4 of the non
      tumorigenic MLEC lines were transfected with cloned activated c-H-ras containing
      a point mutation within codon 61, they all became tumorigenic, the resultant
      neoplasms being hepatocellular carcinomas often associated with albumin mRNA
      expression. Our results thus indicate that ras activation is not necessary for
      immortalization or even for transformation of mouse liver cells in culture, and
      that ras activation may be an event during the progression process in mouse
      hepatocarcinogenesis in vivo.

PMID- 1985881
TI  - Heterotransplantation of human breast carcinomas in nude mice. Correlation
      between successful heterotransplants, poor prognosis and amplification of the HER
      2/neu oncogene.
AB  - Four hundred and thirty-three human breast carcinomas and 23 cell lines derived
      from human breast carcinomas were heterotransplanted in nude mice. Twenty-eight
      tumors and 13 cell lines took and could be serially transplanted. Their human
      origin was established by isozyme analysis performed on successive passages.
      Sixteen primary infiltrating duct-cell carcinomas (PIDC) took, from a total of
      262 transplanted (6.1%). This is in striking contrast to the greater than 50%
      rate of takes of most major cancers of epithelial origin. All 16 PIDC growing in
      nude mice were highly cellular and lacked desmoplastic hyperplasia. The clinical
      prognosis of the PIDC patients whose tumors were successfully transplanted was
      poor. Ten of 16 (63%) died of their disease within 3 years, compared to only 49
      (20%) of the 246 PIDC patients whose tumors did not take in nude mice. This could
      not be attributed to later stage disease of the tumors that took, because only
      15% of these patients had 4 or more positive axillary lymph nodes as opposed to
      28% of the patients whose tumors did not take. Sixty-four percent of the breast
      carcinomas growing in nude mice exhibited amplification of the HER-2/neu oncogene
      which is also correlated with poor prognosis in human breast cancer. It is
      possible that the nude mouse is more susceptible to a population of highly
      invasive and lethal breast carcinomas.

PMID- 1985882
TI  - CA 50 determination in body fluids: can we screen patients at risk for gastric
      cancer?
AB  - CA 50 (a tumor-associated gangliosidic antigen) levels have been determined by an
      RIA test in serum, gastric juice and urine of patients undergoing upper
      gastrointestinal tract endoscopy: 22 control subjects (no macroscopic or
      microscopic lesions), 29 patients with chronic atrophic gastritis, 20 with
      epithelial dysplasia and 16 with gastric cancer entered the study. Gastric juices
      were also tested for pH, protein concentration and specific gravity, urines for
      protein concentration and osmolarity. Serum and gastric juices were also tested
      for CEA levels and the results obtained with the two markers compared. In
      patients with gastric cancer, CA 50 gastric juice levels were statistically
      higher than in controls; a wide overlap was however present among groups, and
      sensitivity and specificity were respectively 38% and 85% for serum and 69% and
      82% for gastric juice. Sensitivity and specificity were respectively 23% and 89%
      for CA 50 determination in urines. In this case, no statistically significant
      difference was observed between gastric cancer and control patients. A trend
      toward higher median values was observed in advanced with respect to early
      gastric cancer. A correlation was found between gastric juice and serum CA 50
      levels, as well as between serum and urine levels of the marker. A correlation
      was also observed between CA 50 values and protein concentration in gastric juice
      and with osmolarity in urines. Overall, CA 50 levels were statistically higher in
      patients with intestinal metaplasia than in those who did not present the lesion.
      Increased CA 50 gastric juice levels are also observed in patients with chronic
      atrophic gastritis and epithelial dysplasia. CA 50 gastric juice and urine levels
      appear to be dependent, at least in part, on the concentration of the fluid.

PMID- 1985883
TI  - Human ovarian cancer xenografts in nude mice: characterization and analysis of
      antigen expression.
AB  - We have characterized 13 different human ovarian cancer xenografts grown
      subcutaneously in nude mice. The tumor lines represented 5 histological subtypes:
      serous (4), mucinous (4), clear-cell carcinoma (1), carcinosarcoma (1) and
      undifferentiated (3). The specific histology and the degree of differentiation
      resembled those of the original patients' tumors and were maintained upon serial
      transfer. Volume doubling times of the xenografts ranged from 3.5 to 15 days. The
      xenografts were also analyzed for their antigen expression using 20 monoclonal
      antibodies (MAbs) reactive with 15 tumor-associated antigens. Immunohistochemical
      examination of tissue sections showed a positive reaction pattern with MAbs
      115D8, 140C1, 139H2, 175C5, HMFG1 and HMFG2, each recognizing episialin, as well
      as with MAbs AUA1, 358.4.32 and 199-157 in xenografts of the serous, mucinous and
      clear-cell carcinoma subtype. MAb OC125 was reactive with xenografts of the
      serous subtypes. Other antibodies, such as 494 and OV-TL3 infrequently
      demonstrated positive reactions. Reactivity of all MAbs was low in the
      carcinosarcoma and undifferentiated tumor lines. With the exception of AUA1, 495
      and 126E5, all MAbs revealed a heterogeneous staining pattern. MAbs against
      episialin and OC125 predominantly stained the apical site of the tumor cells.
      Strongest reactivity with almost all histological subtypes was observed with MAbs
      115D8, 140C1, 139H2 and AUA1. In cases where we were able to compare the
      patients' tumor tissue with the respective xenografts, retention of antigen
      expression was demonstrated in each instance. Release of tumor-associated
      antigens was shown for CA125 in 2 serous-tumor lines, for CA15.3 in 1 serous
      tumor line, and for CEA in 3 lines of the mucinous subtype. This panel of human
      tumor xenografts could be a valuable tool to determine the potential usefulness
      of MAb-guided therapy in ovarian cancer.

PMID- 1985884
TI  - Production of heparanase by normal and neoplastic murine B-lymphocytes.
AB  - The production of heparanase, an endoglycosidase capable of degrading heparan
      sulfate from the subendothelial extracellular matrix (ECM), was investigated in
      various murine B-lymphoid tumors representing distinct maturation stages of the B
      cell lineage. We found that heparanase is produced and released by 3 out of 4 pre
      B lymphomas and by 4 B lymphomas examined. In contrast, 5 plasmacytomas and
      resting normal B lymphocytes, expressed little, if any, heparanase activity.
      Treatment with LPS resulted in high expression of the enzyme by normal B
      lymphocytes, but there was no effect on the constitutive production of heparanase
      by myeloma or B-lymphoma cells. Our results indicate that heparanase is produced
      by B cells during discrete stages of their maturation. We suggest that heparanase
      may play a role in B-cell migration by enabling pre-B and B lymphocytes to leave
      the bone-marrow compartment and recirculate among peripheral lymphoid organs.

PMID- 1985885
TI  - Actin: protein structure and filament dynamics.

PMID- 1985886
TI  - Human lysosomal cathepsin G and granzyme B share a functionally conserved broad
      spectrum antibacterial peptide.
AB  - Human neutrophil lysosomal cathepsin G (cat G) exerts broad-spectrum
      antibacterial action in vitro against Gram-negative and -positive bacteria
      independent of its serine protease activity. We recently determined that an
      internal peptide of cat G (HPQYNQR), obtained after digestion of cat G with
      clostripain, possessed broad-spectrum antibacterial action in vitro, displaying
      an ED50 of 5 x 10(-5) M. In order to evaluate the structure-antibacterial
      properties of this peptide, synthetic variants with single alanine substitutions
      at each position were prepared and tested for antibacterial action. We found that
      alanine substitution for His-1 or Tyr-4, or certain modifications of the His-1
      side chain, produced nonbactericidal peptides. A hexapeptide lacking the COOH
      terminal Arg-7 but not a pentapeptide lacking both Gln-6 and Arg-7 possessed in
      vitro bactericidal activity. Interestingly, the cat G bactericidal peptide
      displays similarity to sequences within other serine proteases, notably the
      proposed cytotoxic granzymes present in the cytolytic granules of human and mouse
      cytotoxic T lymphocytes. We now report that an internal peptide of one human
      granzyme (granzyme B) with the sequence of HPAYNPK also displays bactericidal
      action in vitro. Our results suggest that an internal antibacterial domain among
      human serine proteases cat G and granzyme B has been functionally conserved
      through evolution perhaps for the purpose of host defense against microbial
      pathogens and targets of cytotoxic T lymphocyte killing.

PMID- 1985887
TI  - Proline-valine pseudo peptide enol lactones. Effective and selective inhibitors
      of chymotrypsin and human leukocyte elastase.
AB  - Pro-Val pseudo dipeptides incorporating protio and halo enol lactones were tested
      for inhibitory activity against the serine proteases human leukocyte elastase
      (HLE), porcine pancreatic elastase, alpha-chymotrypsin, trypsin, thrombin, and
      urokinase. The protio enol lactones 1a-c were found to be HLE substrates but were
      poor alternate substrate inhibitors. The bromo enol lactone trans isomer 2a was
      found to be a very effective inhibitor of HLE and chymotrypsin, as shown by the
      binding constants (KI), acylation rates (ka), inactivation rates, and partition
      ratios determined for each enzyme. This inhibitor shows better specificity toward
      its target enzyme HLE than monosubstituted halo enol lactones; we attribute this
      to a pseudo dipeptide acyl enzyme whose structure is similar to that adopted by
      good peptide substrates of HLE. Inactivation of chymotrypsin by the bromo enol
      lactone 2a is permanent, but inactivation of HLE is partially recoverable upon
      treatment with the nucleophile hydrazine, indicating that lactone 2a produces two
      species of inactivated HLE. The more stable of these species could be the result
      of alkylation of His-57 by the electrophilic bromomethyl ketone revealed in the
      acyl enzyme, and the less stable, hydrazine-reactivatable species could be the
      result of alkylation of Asp-102 or the hydrolysis of the bromomethyl ketone group
      in the initially formed acyl enzyme to form a new, more stable acyl enzyme.

PMID- 1985888
TI  - Reconstitution of the phosphoglycerate transport protein of Salmonella
      typhimurium.
AB  - Operation of the phosphoglycerate transport protein (PgtP) of Salmonella
      typhimurium has been studied in proteoliposomes by using a technique in which
      membrane protein is solubilized and reconstituted directly from small volumes of
      cell cultures. When protein from induced cells was reconstituted into phosphate
      (Pi)-loaded proteoliposomes, it was possible to demonstrate a PgtP-mediated
      exchange of internal and external phosphate. For this homologous Pi:Pi antiport,
      kinetic analysis indicated a Michaelis constant (Kt) of 1 mM and a maximal
      velocity of 26 nmol/min mg of protein; arsenate inhibited with a Ki of 1.3 mM,
      suggesting that PgtP did not discriminate between these two inorganic substrates.
      Pi-loaded proteoliposomes also accumulated 3-phosphoglycerate and
      phosphoenolpyruvate, establishing for each of them a concentration gradient
      (in/out) of about 100-fold; phosphoenolpyruvate (Ki = 70 microM) rather than 3
      phosphoglycerate (Kt = 700, Ki = 900 microM) was the preferred substrate for
      these conditions. We also concluded that such heterologous exchange was a neutral
      event, since its rate and extent were unaffected by the presence of a
      protonophore and unresponsive to the imposition of a membrane potential (positive
      or negative inside). In quantitative work, we found a stoichiometry of 1:1 for
      the exchange of Pi and 3-phosphoglycerate, and given an electroneutral exchange,
      this finding is most easily understood as the overall exchange of divalent Pi
      against divalent phosphoglycerate. These experiments establish that PgtP
      functions as an anion exchange protein and that it shares important mechanistic
      features with the Pi-linked antiporters, GlpT and UhpT, responsible for transport
      of glycerol 3-phosphate and hexose 6-phosphates into Escherichia coli.

PMID- 1985889
TI  - Purification and functional characterization of glutamate-1-semialdehyde
      aminotransferase from Chlamydomonas reinhardtii.
AB  - The formation of delta-aminolevulinic acid, the first committed precursor of
      chlorophyll biosynthesis, occurs in the chloroplast of plants and algae by the C5
      pathway, a three-step, tRNA-dependent transformation of glutamate. Previously, we
      reported the purification and characterization of the first two enzymes of this
      pathway, glutamyl-tRNA synthetase and Glu-tRNA reductase from the green alga
      Chlamydomonas reinhardtii (Chen, M.-W., Jahn, D., Schon, A., O'Neill, G. P., and
      Soll, D. (1990) J. Biol. Chem. 265, 4054-4057 and Chen, M.-W., Jahn, D., O'Neill,
      G. P., and Soll, D. (1990) J. Biol. Chem. 265, 4058-4063). Here we present the
      purification of the third enzyme of the pathway, the glutamate-1-semialdehyde
      aminotransferase from C. reinhardtii. The enzyme was purified from the membrane
      fraction of a whole cell extract employing four different chromatographic
      separations. The apparent molecular mass of the protein was approximately 43,000
      Da as analyzed by denaturing sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis, by nondenaturing rate zonal sedimentation on glycerol gradients,
      and by gel filtration. By these criteria, the enzyme in its active form is a
      monomer of 43,000 Da. In the presence of pyridoxal 5'-phosphate, purified
      glutamate-1-semialdehyde aminotransferase converts synthetic glutamate 1
      semialdehyde to delta-aminolevulinic acid. The enzyme is inhibited by gabaculine
      and aminooxyacetate, both typical inhibitors of aminotransferases. The purified
      glutamate-1-semialdehyde aminotransferase successfully reconstitutes the whole C5
      pathway in vitro from glutamate in the presence of purified glutamyl-tRNA
      synthetase, glutamyl-tRNA reductase, Mg2+, ATP, NADPH, tRNA, and pyridoxal 5'
      phosphate.

PMID- 1985890
TI  - Distinct mechanisms of regulation of protein kinase C epsilon by hormones and
      phorbol diesters.
AB  - In this study, we examined the effects of T cell activators on the regulation of
      protein kinase C (PKC) isozymes present in thymocytes. Using affinity-purified
      anti-PKC antisera, we determined that the major PKC isoforms in murine thymocytes
      are PKC beta and PKC epsilon. The CD4+/CD8+ thymocyte subset expressed high
      levels of both PKC beta and PKC epsilon, whereas the CD4-/CD8- subset expressed
      much less of both. PKC beta was down-regulated following treatment of thymocytes
      with phorbol 12-myristate acetate (PMA) (2 x 10(-8) M) or ionomycin (0.4 microM).
      In contrast, PMA did not induce the down-regulation of PKC epsilon. Ionomycin
      alone, however, induced PKC epsilon down-regulation, similar to its effect on PKC
      beta. Similar observations were made on a promonocytic cell line, U937, which
      expresses PKC alpha, PKC beta (Strulovici, B., Daniel-Issakani, S., Oto, E.,
      Nestor, J., Jr., Chan, H., and Tsou, A.-P. (1989) Biochemistry 28, 3569-3576),
      and PKC epsilon. To facilitate the study of PKC beta and PKC epsilon, we
      established a Chinese hamster ovary cell line which expresses murine PKC epsilon
      in addition to endogenous PKC alpha and PKC beta. Both PKC isoforms (beta and
      epsilon) were mostly in particulate form. PMA treatment left the majority of
      immunoreactive PKC epsilon intact. By contrast, thrombin treatment caused the
      disappearance of particulate and cytosolic PKC epsilon (60% by 10 min and 80% by
      1 h). PMA and thrombin promoted the down-regulation of PKC beta with similar
      kinetics (100% down-regulation by 3 h). These results indicate that: 1)
      thymocytes express PKC epsilon; and 2) this isozyme exhibits a novel form of
      regulation distinct from the other PKC isozymes.

PMID- 1985891
TI  - Thrombin- and histamine-induced signal transduction in human endothelial cells.
      Stimulation and agonist-dependent desensitization of protein phosphorylation.
AB  - Treatment of human endothelial cells with thrombin, histamine, or
      dioctanoylglycerol (DiC8), a synthetic diacylglycerol, resulted in the rapid and
      transient phosphorylation of a Mr = 29,000 protein (P29) in a dose-dependent
      manner. Various tumor promoters also promoted P29 phosphorylation while the
      adenylate cyclase activator, forskolin, did not. The level of phosphorylation
      with all three agonists was similar (2.5-4 fold), and analysis of P29 by two
      dimensional gel electrophoresis revealed identical patterns in each case.
      Receptor specificity was demonstrated for the histamine-stimulated changes;
      pyrilamine (10(-6) M; H1) but not cimetidine (10(-4); H2) blocked the response.
      The thrombin effect was active site-dependent. Phosphorylation induced by
      thrombin and histamine occurred within 1 min, peaked between 5 and 10 min, and
      returned to control levels by 1 h. DiC8-induced phosphorylation occurred more
      slowly but was also reduced by 1 h while phorbol ester treatment prolonged
      phosphorylation for at least 4 h. Treatment of these cells with thrombin or
      histamine for 1 h desensitized P29 to further phosphorylation by the homologous
      agonist although secondary phosphorylation could occur with heterologous
      compounds. However, if the primary agonist was removed following the onset of a
      desensitized state, secondary phosphorylation of P29 could be stimulated by the
      same compound. These same results were observed with two other phosphoproteins Mr
      = 18,000 (P18) and 80,000 (P80) which became more highly phosphorylated in
      response to thrombin treatment and with histamine/thrombin-stimulated
      prostaglandin I2 production. In contrast, homologous down-regulation of P29
      phosphorylation was not observed with DiC8-treated cells, and the decline in
      phosphorylated P29 was associated with the loss of functional DiC8. The protein
      kinase inhibitors staurosporine and H-7 blocked P18 and P80 phosphorylation by
      thrombin but had no effect on P29 phosphorylation by histamine, thrombin, or DiC8
      suggesting distinct pathways leading to the phosphorylation of these different
      proteins. These data suggest that multiple and independent thrombin/histamine
      induced events are susceptible to receptor occupancy-dependent homologous down
      regulation.

PMID- 1985892
TI  - Effect of potassium ions and membrane potential on the Na-Ca-K exchanger in
      isolated intact bovine rod outer segments.
AB  - Two recent studies reported that Na-Ca exchange in the outer segments of tiger
      salamander rod photoreceptors (Cervetto, L., Lagnado, L., Perry, R. J., Robinson,
      D. W., and McNaughton, P. A. (1989) Nature 337, 740-743) and of bovine rod
      photoreceptors (Schnetkamp, P. P. M., Basu, D. K., and Szerencsei, R. T. (1989)
      Am. J. Physiol. 257, C153-157) requires and transports K+ in a 4Na/(1Ca+1K)
      stoichiometry. In this study, we have examined the effects of K+ ions and
      membrane potential on the kinetics of Na-Ca and Ca-Ca exchange in rod outer
      segments isolated from bovine retinas. The objective was to establish the ion
      selectivity and voltage dependence of the different cation binding sites on the
      Na-Ca-K exchange protein. Potassium ions activated Na-Ca exchange when present on
      the Ca2+ side, although the extent of activation decreased with decreasing Na+
      concentration. Potassium ions inhibited Na-Ca exchange when present on the Na+
      side; inhibition arose from competition between Na+ and K+ for a common single
      cation-binding site. Activation of Na-Ca exchange by K+ displayed a different ion
      selectivity than that observed for inhibition of Na-Ca exchange by K+. The
      results are interpreted in terms of a three-site model for the rod Na-Ca-K
      exchanger. The rate of forward Na-Ca exchange decreased by 1.75-fold for a 60 mV
      depolarization of the plasma membrane but only at lower Na+ concentrations. The
      rate of Ca-Ca exchange was not affected by changes in membrane potential.

PMID- 1985893
TI  - Unidirectional Na+, Ca2+, and K+ fluxes through the bovine rod outer segment Na
      Ca-K exchanger.
AB  - The properties of the Na-Ca exchanger in the plasma membrane of rod outer
      segments isolated from bovine retinas (ROS) were studied. Unidirectional Ca2+,
      Na+, and K+ fluxes were measured with radioisotopes and atomic absorption
      spectroscopy. We measured K+ fluxes associated with the Ca-Ca self-exchange mode
      of the Na-Ca exchanger to corroborate our previous conclusion that the ROS Na-Ca
      exchanger differs from Na-Ca exchangers in other tissues by its ability to
      transport K+ (Schnetkamp, P. P. M., Basu, D. K. & Szerencsei, R. T. (1989) Am. J.
      Physiol. 257, C153-C157). The Na-Ca-K exchanger was the only functional cation
      transporter in the plasma membrane of bovine ROS with an upper limit of a flux of
      10(5) cations/ROS/s or a current of 0.01 pA contributed by other cation channels,
      pumps, or carriers; cation fluxes via the Na-Ca-K exchanger amounted to 5 x 10(6)
      cations/ROS/s or a current of 1 pA. Ca2+ efflux via the forward mode of the Na-Ca
      K exchanger did not operate with a fixed single stoichiometry. 1) The Na/Ca
      coupling ratio was increased from three to four when ionophores were added that
      could provide electrical compensation for the inward Na-Ca exchange current. 2)
      The K/Ca coupling ratio could vary by at least 2-fold as a function of the
      external Na+ and K+ concentration. The results are interpreted in terms of a
      model that can account for the variable Ca/K coupling ratio: we conclude that the
      Ca2+ site of the exchanger can translocate independent of translocation of the K+
      site, whereas translocation of the K+ site requires occupation of the Ca2+ site,
      but not its translocation. The results are discussed with respect to the
      physiological role of Na-Ca-K exchange in rod photoreceptors.

PMID- 1985894
TI  - Evidence that both arginine 102 and arginine 747 are involved in substrate
      binding to neutral endopeptidase (EC 3.4.24.11).
AB  - Neutral endopeptidase (EC 3.4.24.11, NEP) is a Zn-metallopeptidase involved in
      the degradation of biologically active peptides, notably the enkephalins and
      atrial natriuretic peptide. Recently, the structure of the active site of this
      enzyme has been probed by site-directed mutagenesis, and 4 amino acid residues
      have been identified, namely 2 histidines (His583 and His587), which act as zinc
      binding ligands, a glutamate (Glu584) involved in catalysis, and an arginine
      residue (Arg102), suggested to participate in substrate binding. Site-directed
      mutagenesis has now been used to investigate the role of 4 other arginine
      residues (Arg408, Arg409, Arg659, and Arg747) that have been proposed as possible
      active site residues and to further analyze the role of Arg102. In each case, the
      arginine was replaced with a methionine, and both enzymatic activity and the IC50
      values of several NEP inhibitors were measured for the mutated enzymes and
      compared to wild-type enzyme. The results suggest that 2 arginines, Arg102 and
      Arg747, could both be important for substrate and inhibitor binding. Arg747 seems
      to be positioned to interact with the carbonyl amide group of the P'1 residue and
      can be modified when the enzyme is treated with the arginine-specific reagents
      phenylglyoxal and butanedione. Arg102 could be positioned to interact with the
      free carboxyl group of a P'2 residue in some substrates and inhibitors and can be
      modified by phenylglyoxal but not by butanedione. The results could explain the
      dual dipeptidylcarboxypeptidase and endopeptidase nature of NEP.

PMID- 1985895
TI  - Structure of the human laminin B2 chain gene reveals extensive divergence from
      the laminin B1 chain gene.
AB  - The exon-intron structure of the human laminin B2 chain gene was elucidated from
      genomic lambda phage clones spanning 2 kilobase pairs (kb) of the 5'-flanking
      region, 58 kb of the structural gene and 10 kb of the 3'-flanking region. The
      entire gene was shown to contain 28 exons. The promoter region has no TATA or
      CAAT boxes whereas it contains five GC boxes and three AP-2-like binding sites.
      Comparison with the promoter region of the mouse gene revealed six highly
      conserved sequences of 14 to 42 base pairs in length. Sequencing of the last exon
      of the gene showed that the 3'-untranslated region of the mRNA can be up to 2797
      nucleotides with five AATAAA potential polyadenylation signals. The similarity of
      the human 3'-untranslated sequence with that of mouse was shown to be 68.8%. The
      exon-intron structure of the laminin B2 chain gene demonstrated extensive
      divergence from the human laminin B1 chain gene, which has 34 exons. Only three
      intron locations are conserved in these two genes. The overall exon profile of
      the laminin B2 chain gene correlates only marginally with the pattern of
      structural domains and internal cysteine-rich repeats in the laminin B2
      polypeptide chain.

PMID- 1985897
TI  - DNA binding of purified transcription factor NF-kappa B. Affinity, specificity,
      Zn2+ dependence, and differential half-site recognition.
AB  - A rapid purification procedure for the NF-kappa B transcription factor from the
      cytosol of human placenta is demonstrated which exploits the insensitivity of the
      NF-kappa B.DNA complex toward the intercalating agent chloroquine. Purified NF
      kappa B required 100 mM KCl or NaCl and a pH of 7.5 to optimally bind to DNA.
      Equilibrium of binding was reached within less than 5 min in the absence of
      competitor DNA and after 1 h in the presence of 0.1 mg/ml poly(dI-dC). DNA
      binding of NF-kappa B was specifically blocked by the chelating agent 1,10
      orthophenantroline and could only be reconstituted by addition of Zn2+. Under
      optimal binding conditions, the dissociation constant for the complex of the
      purified NF-kappa B with its most frequent cognate DNA motif 5'-GGGACTTTCC-3' was
      in the range of 10(-12) to 10(-13) M. Various other cis-acting kappa B motifs
      were recognized by NF-kappa B with lower affinities. A comparative analysis of
      known NF-kappa B-binding sites and competition experiments with synthetic
      polynucleotides and oligonucleotides encompassing only one half-site or single
      stranded kappa B motifs suggested that the two DNA-binding monomers in the NF
      kappa B protein complex can interact differentially with the half-sites of the
      decameric cognate motif.

PMID- 1985896
TI  - Amino acid sequence of an anti-tumor protein from Rana pipiens oocytes and early
      embryos. Homology to pancreatic ribonucleases.
AB  - Rana pipiens oocytes and early embryos contain large amounts of a basic protein
      with antiproliferative/cytotoxic activity against several tumor cell lines in
      vitro (Darzynkiewicz, Z., Carter, S. P., Mikulski, S. M., Ardelt, W., and Shogen,
      K. (1988) Cell Tissue Kinet. 21, 169-182; Mikulski, S.M., Viera, A., Ardelt, W.,
      Menduke, H., and Shogen, K. (1990) Cell Tissue Kinet. 23, 237-246), as well as
      antitumor activity in vivo (Mikulski, S. M., Ardelt, W., Shogen, K., Bernstein,
      E. H., and Menduke, H. (1990) J. Natl. Cancer Inst. 82, 151-153). The protein,
      provisionally named P-30 Protein, was purified to homogeneity from early embryos
      and characterized. It is a single-chain protein consisting of 104 amino acid
      residues in the following sequence: less than Glu1-Asp-Trp-Leu-Thr-Phe-Gln-Lys
      Lys-His-Ile-Thr-Asn-Thr- Arg15-Asp-Val-Asp-Cys-Asp-Ans-Ile-Met-Ser-Thr-Asn-Leu
      Phe-His-C ys30-Lys-Asp-Lys - Asn-Thr-Phe-Ile-Tyr-Ser-Arg-Pro-Glu-Pro-Val-Lys45
      Ala-Ile-Cys-Lys- Gly-Ile-Ile- Ala-Ser-Lys-Asn-Val-Leu-Thr-Thr60-Ser-Glu-Phe-Tyr
      Leu-Ser-Asp -Cys-Asn-Val-Thr-Ser-Arg-Por-Cys75-Lys-Tyr-Lys-Leu-Lys-Lys-Ser-Thr 
      Asn-Lys-Phe- Cys-Val-Thr-Cys90-Glu-Asn-Gln-Ala-Pro-Val-His-Phe-Val-Gly-Val-Gly-
      Ser-Cys104-OH . Its molecular weight calculated from the sequence is 11,819. The
      sequence homology clearly indicates that the protein belongs to the superfamily
      of pancreatic ribonuclease. It is also demonstrated that it indeed exhibits a
      ribonucleolytic activity against highly polymerized RNA and that this activity
      seems to be essential for its antiproliferative/cytotoxic effects.

PMID- 1985898
TI  - Role of protein kinase C in the regulation of glucose transport in the rat
      adipose cell. Translocation of glucose transporters without stimulation of
      glucose transport activity.
AB  - The possible role of protein kinase C in the regulation of glucose transport in
      the rat adipose cell has been examined. Both insulin and phorbol 12-myristate 13
      acetate (PMA) stimulate 3-O-methylglucose transport in the intact cell ein
      association with the subcellular redistribution of glucose transporters from the
      low density microsomes to the plasma membranes, as assessed by cytochalasin B
      binding. In addition, the actions of insulin and PMA on glucose transport
      activity and glucose transporter redistribution are additive. Furthermore, PMA
      accelerates insulin's stimulation of glucose transport activity, reducing the
      t1/2 from 3.2 +/- 0.4 to 2.1 +/- 0.2 min (mean +/- S.E.). However, the effect of
      PMA on glucose transport activity is approximately 10% of that for insulin
      whereas its effect on glucose transporter redistribution is approximately 50% of
      the insulin response. Immunoblots of the GLUT1 and GLUT4 glucose transporter
      isoforms in subcellular membrane fractions also demonstrate that the
      translocations of GLUT1 in response to PMA and insulin are of similar magnitude
      whereas the translocation of GLUT4 in response to insulin is markedly greater
      than that in response to PMA. Thus, glucose transport activity in the intact cell
      with PMA and insulin correlates more closely with the appearance of GLUT4 in the
      plasma membrane than cytochalasin B-assayable glucose transporters. Although
      these data do not clarify the potential role of protein kinase C in the mechanism
      of insulin action, they do suggest that the mechanisms through which insulin and
      PMA stimulate glucose transport are distinct but interactive.

PMID- 1985899
TI  - Evidence for bile acid-evoked oscillations of Ca2(+)-dependent K+ permeability
      unrelated to a D-myo-inositol 1,4,5-trisphosphate effect in isolated guinea pig
      liver cells.
AB  - In single liver cells, the D-myo-inositol 1,4,5-triphosphate (InsP3)-dependent
      agonists such as noradrenaline and angiotensin II evoke oscillations in
      intracellular calcium [Ca2+]i resulting mostly from the periodic release and
      reuptake of calcium from intracellular stores. In the present work, we have
      reexamined the effects of these agonists and investigated whether the natural
      bile acid taurolithocholic acid 3-sulfate (TLC-S), which permeabilizes the
      endoplasmic reticulum, could initiate oscillations of [Ca2+]i. Oscillations of
      [Ca2+]i were monitored with the Ca2(+)-dependent K+ permeability in whole-cell
      voltage-clamped guinea pig liver cells. Our results confirm the presence of two
      types of oscillations induced by hormones. They could be distinguished by their
      frequency periods. The fast (type I) had periods ranging from 5 to 12 s and the
      slow (type II) from 60 to 240 s. They have been respectively attributed to second
      messenger- and receptor-controlled oscillations, respectively. Our results also
      show that TLC-S, as noradrenaline and angiotensin II, induced the activation of
      this Ca(+)-dependent K+ current and was able to reproduce both types of
      oscillations. The bile acid effect was not blocked by intracellular perfusion of
      heparin known to inhibit both InsP3 binding and InsP3-evoked Ca2+ release in
      several tissues. In these conditions, TLC-S only evoked type I oscillations,
      suggesting that these fluctuations could originate from a mechanism that is
      independent of InsP3 and is an intrinsic property of internal Ca2+ stores.

PMID- 1985900
TI  - Stopped-flow investigation of the reaction of vitamin C with tocopheroxyl radical
      in aqueous triton X-100 micellar solutions. The structure-activity relationship
      of the regeneration reaction of tocopherol by vitamin C.
AB  - A kinetic study of the reaction between vitamin C (L-ascorbic acid, AsH2) and a
      tocopheroxyl radical (7-tert-butyl-5-isopropyltocopheroxyl) in Triton X-100
      micellar solution has been performed using stopped-flow spectrophotometry. The
      second-order rate constants (k2) obtained showed notable pH dependence with a
      broad maximum around pH 8. For instance, the k2 values obtained were 26 M-1 S-1
      at pH 3, 322 M-1 S-1 at pH 7, and 273 M-1 S-1 at pH 10. A good correlation
      between the rate constants and the mole fraction of ascorbate monoanion (AsH-)
      was observed, showing that ascorbate (AsH-) can regenerate the tocopherol from
      tocopheroxyl in biological systems. Furthermore, the results indicate that
      reduced ascorbic acid (AsH2) does not have the ability to regenerate the
      tocopherol in aqueous solution. On the other hand, it was found that AsH2 can
      reduce the tocopheroxyl to tocopherol in benzene/ethanol (2:1) mixtures, although
      the rate of reaction is only approximately 15% of that observed in micellar
      solution at pH 7.

PMID- 1985901
TI  - In vivo competition between iron and manganese for occupancy of the active site
      region of the manganese-superoxide dismutase of Escherichia coli.
AB  - Three forms of the dimeric manganese superoxide dismutase (MnSOD) were isolated
      from aerobically grown Escherichia coli which contained 2 Mn, 1 Mn and 1 Fe, or 2
      Fe, respectively. These are designated Mn2-MnSOD, Mn,Fe-MnSOD, and Fe2-MnSOD.
      Substitution of iron in place of manganese, eliminated catalytic activity,
      decreased the isoelectric point, and increased the native electrophoretic anodic
      mobility, although circular dichroism, high performance liquid chromatography gel
      exclusion chromatography, and sedimentation equilibrium revealed no gross changes
      in conformation. Moreover, replacement of iron by manganese restored enzymatic
      activity. Fe2-MnSOD and the iron-superoxide (FeSOD) of E. coli exhibit distinct
      optical absorption spectra. These data indicate that the active site environments
      of E. coli MnSOD and FeSOD must differ. They also indicate that competition
      between iron and manganese for nascent MnSOD polypeptide chains occurs in vivo,
      and copurification of these variably substituted MnSODs can explain the
      substoichiometric manganese contents and the variable specific activities which
      have been reported for this enzyme.

PMID- 1985902
TI  - A mouse carcinoembryonic antigen gene family member is a calcium-dependent cell
      adhesion molecule.
AB  - Carcinoembryonic antigen (CEA) is a heavily glycosylated protein used clinically
      as a tumor marker to detect recurrences of many types of tumors. This
      glycoprotein belongs to the immunoglobulin superfamily and is the prototype of
      the large CEA family of proteins. In a concerted effort to determine the
      function(s) of this family, we have been investigating a similar family of
      proteins in the mouse. In this paper, we report the characterization of a new
      mouse family member named mmCGM2; this gene product is highly homologous to the
      human biliary glycoprotein of the CEA gene family and to a rat hepatocyte ecto
      ATPase. In vitro transcription, translation, and glycosylation experiments have
      revealed that the mmCGM2 cDNA encodes a glycoprotein of 42 kDA with a putative
      extracellular N-terminal domain and a C2-set type immunoglobulin domain. We have
      used this cDNA as a probe to detect many different transcripts (1.5-4.6
      kilobases) in mouse adult tissues, some of which are specific to particular
      tissues, while others are expressed ubiquitously. After transfection of a plasmid
      bearing the mmCGM2 cDNA into mouse fibroblasts known to lack CEA-related gene
      expression, transfectant cell clones were chosen and used to investigate the
      adhesion properties conferred onto the cells. Cells expressing the mmCGM2 cDNA in
      a sense orientation aggregated in a calcium- and temperature-dependent fashion.
      Together with human biliary glycoprotein, the mmCGM2 gene product is the first
      member of the immunoglobulin superfamily to exhibit calcium-dependent adhesion.
      The constant tissue reorganization necessary to the differentiation of precise
      structures in tissues which express these gene family members (colon, liver, and
      uterus) implies the necessity of a variety of specific cell-cell contacts which
      could utilize the cell adhesion properties that we have demonstrated.

PMID- 1985903
TI  - A large chondroitin sulfate basement membrane-associated proteoglycan exists as a
      disulfide-stabilized complex of several proteins.
AB  - Proteoglycan (PG)-1000 (formerly TAP-1) is a large (Mr = 10(6)) highly
      glycosylated chondroitin sulfate proteoglycan found associated with Schwann cell
      and electrocyte basement membranes in elasmobranch electric fish. Previously,
      purified PG-1000 was visualized in the electron microscope as a "bottlebrush"
      structure about 345 nm long with about 20 side projections of 113 nm. This
      molecule was characterized with material purified from electric organ under
      denaturing and reducing conditions. Here we report that PG-1000, when purified
      under denaturing conditions without exposure to a reducing agent, exists as a
      complex of several proteins. In addition to PG-1000, this complex consists of a
      somewhat smaller, heavily glycosylated protein (beta component) and three smaller
      proteins with Mr values of 39,000, 21,000, and 18,000. The complex remains intact
      when exposed to denaturing and non-reducing conditions but falls apart in
      denaturing and reducing conditions. Presumably the complex is stabilized by
      disulfide bonds. The beta component of the PG-1000 complex is probably a
      proteoglycan. However, unlike PG-1000, the beta component does not contain
      chondroitin sulfate chains and lacks the epitope, T1, that is found on PG-1000.
      Both molecules share a protease-insensitive antigenic site, SV4, which is
      probably a modified keratan sulfate epitope. Evidence for the identity of this
      antigen is that it is found as a minor subfraction in commercial preparations of
      shark cartilage chondroitin and corneal keratan sulfates but not in other
      glycosaminoglycan preparations. These SV4 antigens are resistant to chondroitin
      ABC lyase digestion. However, the SV4 antigen in commercial keratan sulfate is
      cleaved by keratinase to a smaller antigenic fragment.

PMID- 1985904
TI  - Gastrin-amidating enzyme in the porcine pituitary and antrum. Characterization of
      molecular forms and substrate specificity.
AB  - As is the case with many other peptide hormones of the brain and intestine, the
      formation of biologically active gastrin from a glycine-extended processing
      intermediate occurs via the action of a peptidylglycyl alpha-amidating
      monooxygenase (PAM). The observation that gastrin exists primarily as unamidated
      precursors in the pituitary but as amidated gastrin in the antrum prompted this
      study to examine whether the amidating enzymes in the two organs were different
      in their characteristics. Amidating activity was quantified by measuring the
      conversion of glycine-extended tridecagastrin (G13-Gly) to amidated
      tridecagastrin and glycine-extended hexapancreatic polypeptide (PP6-Gly) to
      amidated hexapancreatic polypeptide by radio-immunoassay. Two molecular forms of
      amidating activity were identified in both the porcine antrum and pituitary. The
      first, PAM-A, had an apparent Mr of 51,000 and a net negative charge at pH 7.0,
      whereas PAM-B was smaller (Mr approximately 30,000) and had a net positive charge
      at pH 7.0. Both molecular forms were similar in their cofactor requirements
      (copper, ascorbic acid, and catalase) and pH optima in the antrum and pituitary.
      The Km was significantly lower and the Vmax higher for PP6-Gly than for G13-Gly
      in the pituitary and antrum. These data suggest that although there is no
      difference between antral and pituitary PAM, the selective affinity of PAM for
      certain substrates may provide a mechanism for the differential amidation of
      different hormones within a given tissue or cell.

PMID- 1985905
TI  - Use of the polymerase chain reaction to clone and sequence a cDNA encoding the
      bovine alpha 3 chain of type IV collagen.
AB  - A novel type IV collagen, alpha 3(IV), has previously been isolated from a
      collagenase digest of bovine and human glomerular and lens basement membranes.
      The cloning and sequencing of a cDNA encoding the alpha 3(IV) chain is described
      here. Using the polymerase chain reaction, with primers derived from the known 27
      residue bovine alpha 3(IV) amino acid sequence, a 68-base pair bovine genomic
      fragment (KEM68) which encodes the known peptide sequence, was synthesized. KEM68
      was then used to screen a bovine lens cDNA library and a 1.5-kilobase partial
      cDNA clone obtained, encoding 471 residues of the bovine alpha 3(IV) chain: 238
      residues from the triple helical collagenous domain and all 233 residues of the
      noncollagenous domain. The collagenous repeat sequence has three interruptions,
      coinciding with those in the alpha 1(IV) chain. The noncollagenous domain has 12
      cysteine residues in identical positions to those of other type IV collagens and
      71, 61, and 70% overall similarity with the human alpha 1(IV), alpha 2(IV), and
      alpha 5(IV) chains. The noncollagenous domain of alpha 3(IV) is of particular
      interest as it appears to be the component of glomerular basement membrane that
      reacts maximally with the Goodpasture antibody. Furthermore, such antigenicity is
      absent from collagenase digests of the glomerular basement membrane of some
      patients with Alport syndrome. The alpha 3(IV) cDNA clone described here now
      permits study of the molecular pathology of COL4A3 in Alport syndrome.

PMID- 1985906
TI  - Multisite phosphorylation of a synthetic peptide derived from the carboxyl
      terminus of the ribosomal protein S6.
AB  - The synthetic peptide AKRRRLSSLRASTSKSESSQK (S6-21) which corresponds to the
      carboxyl-terminal 21 amino acids of human ribosomal protein S6 was synthesized
      and tested as a substrate for S6/H4 kinase purified from human placenta. The
      specific activity of the enzyme with the synthetic peptide and 40 S ribosomes was
      45 and 23 nmol/min/mg, respectively. The S6/H4 kinase activity with S6-21 was
      greater than the enzyme activity with any other substrate tested, including
      histones, protamine, and casein and several other synthetic peptides. The
      phosphorylation of the peptide was not inhibited by inhibitors of several other
      proteins kinases. S6/H4 kinase catalyzed the phosphorylation of three major sites
      in the synthetic peptide and the 40 S ribosomes. A fourth site in S6-21 was
      phosphorylated more slowly. The principal phosphorylation sites were serines in
      the acidic carboxyl-terminal domain of the peptide. A serine (Ser-7 or -8) in the
      amino-terminal domain was phosphorylated at approximately 25% the rate of the
      carboxyl-terminal domain serines. The data suggest that multiple S6 kinases may
      be required to phosphorylate S6 at all five sites which are modified in vivo.

PMID- 1985907
TI  - Phosphorylation of cardiac and skeletal muscle calsequestrin isoforms by casein
      kinase II. Demonstration of a cluster of unique rapidly phosphorylated sites in
      cardiac calsequestrin.
AB  - Calsequestrin is an acidic Ca2(+)-binding protein of sarcoplasmic reticulum
      existing as different gene products in cardiac muscle and skeletal muscle. A
      unique feature of cardiac calsequestrin is a 31-amino acid-long COOH-terminal
      tail (Scott, B. T., Simmerman, H. K. B., Collins, J. H., Nadal-Ginard, B., and
      Jones, L. R. (1988) J. Biol. Chem. 263, 8958-8964), which is highly acidic and
      contains several consensus phosphorylation sites for casein kinase II. In the
      work described here, we tested whether this cardiac-specific sequence is a
      substrate for casein kinase II. Both cardiac and skeletal muscle calsequestrins
      were phosphorylated by casein kinase II, but cardiac calsequestrin was
      phosphorylated to a higher stoichiometry and at least 50 times more rapidly. The
      site of rapid phosphorylation of cardiac calsequestrin was localized to the
      distinct COOH terminus, where a cluster of three closely spaced serine residues
      are found (S378DEESN-DDSDDDDE-COOH). The slower phosphorylation of skeletal
      muscle calsequestrin occurred at its truncated COOH terminus, at threonine
      residue 363 (I351NTEDDDDDE-COOH). The similar sequence in cardiac calsequestrin
      (I351NTEDDDNEE) was not phosphorylated. Cardiac calsequestrin, as isolated,
      already contained 1.2 mol of Pi/mol of protein, whereas skeletal muscle
      calsequestrin contained only trace levels of Pi. The endogenous Pi of cardiac
      calsequestrin was also localized to the distinct COOH terminus. Our results
      indicate that the cardiac isoform of calsequestrin is the preferred substrate for
      casein kinase II both in vivo and in vitro.

PMID- 1985908
TI  - Streptococcal protein G. Gene structure and protein binding properties.
AB  - Protein G was solubilized from 31 human group C and G streptococcal strains with
      the muralytic enzyme mutanolysin. As judged by the mobility in sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis and the binding patterns of the
      solubilized protein G molecules in Western blot experiments, the strains could be
      divided into three groups, represented by the group G streptococcal strains G148
      and G43 and the group C streptococcal strain C40. The 65-kDa G148 protein G and
      the 58-kDa C40 protein G showed affinity for both immunoglobulin G (IgG) and
      human serum albumin (HSA), whereas the 40-kDa G43 protein G bound only IgG.
      Despite the different molecular patterns, the three protein G species had
      identical NH2-terminal amino acid sequences. Apart from the 65-kDa peptide,
      digestion of G148 streptococci with mutanolysin also produced a 52-kDa IgG- and
      HSA-binding peptide and a 14-kDa HSA-binding peptide. It was demonstrated that
      these peptides resulted from cleavage of 65-kDa protein G by proteolytic
      components in the mutanolysin preparation. The protein G genes of the C40 and G43
      strains were cloned and sequenced, and their structure was compared to the
      previously published sequence of the G148 protein G gene. As compared to G148,
      both the C40 and G43 genes lacked a 210-base pair fragment in the IgG-binding
      region, accounting for the 10-fold lower affinity of these proteins for IgG. The
      G43 gene also lacked a 450-base pair fragment in the 5'-end of the gene,
      explaining why the G43 protein G did not bind HSA. The differences in protein G
      structure did not correlate with the clinical origin of the strains used in this
      study. The IgG-binding region of protein G was further mapped. Thus, a peptide
      corresponding to a single IgG-binding unit was obtained by the cloning and
      expression of a 303-base pair polymerase chain reaction-generated DNA fragment.
      The affinity of this 11.5-kDa peptide for human IgG was 8.0 x 10(7) M-1, as
      determined by Scatchard plots. Finally, a 55-amino acid-long synthetic peptide,
      corresponding to one of the three repeated domains in the COOH-terminal half of
      strain G148 protein G, effectively blocked binding of protein G to IgG.

PMID- 1985909
TI  - Activation of protein kinase C in lipid monolayers.
AB  - The potential of lipid monolayers spread at an air-water interface was
      investigated as a well defined membrane model able to support protein kinase C
      (PKC) association and activation. PKC association to a mixed phospholipid film
      (phosphatidylcholine, phosphatidylserine) could be detected by an increase of the
      monolayer surface pressure. This association was strikingly dependent upon the
      presence of submicromolar concentrations of Ca2+. The effect of Ca2+ resulted in
      an increase of the PKC penetration into the lipid core at a given permissive
      surface pressure as well as in a marked increase of the critical surface pressure
      (29-38 dynes/cm) above which the enzyme was excluded from the membrane. Inclusion
      of diacylglycerol or tetradecanoate phorbol acetate (TPA) did not modify the PKC
      monolayer association in a detectable manner. PKC associated to the lipid layer
      exhibited the expected catalytic property and was fully activated when
      diacylglycerol or TPA was included in the membrane. PKC activity was highly
      dependent upon the surface pressure of the lipid monolayer, being optimal between
      30 and 35 dynes/cm. Study of the compression isotherm of various diacylglycerol
      structures revealed that all potent PKC agonists exhibited an expanded liquid
      phase behavior with collapse pressure below 40 dynes/cm, in contrast to weak
      activators which showed condensed isotherms with high collapse pressure
      (approximately equal to 60 dynes/cm). These observations showed that the lipid
      monolayer system is well adapted to the study of the molecular mechanisms
      involved in the regulation of PKC activity at a model membrane interface. They
      are in line with the suggestion of a major role of Ca2+ in the association
      (translocation) of PKC to membrane in living cell and suggest that diacylglycerol
      (and TPA) might activate membrane-associated PKC through local change in the
      surrounding lipid phase organization.

PMID- 1985910
TI  - Cellular expression of mutant insulin receptors interferes with the rapid
      transcriptional response to both insulin and insulin-like growth factor I.
AB  - We examined the expression of the proto-oncogene c-fos and the early growth
      response gene, Egr-1, in Rat 1 fibroblasts expressing high levels of normal or
      mutated human insulin receptors (McClain, D. A., Maegawa, H., Lee, J., Dull, T.
      J., Ullrich, A., and Olefsky, J. M. (1987) J. Biol. Chem. 262, 14663-14671). In
      cells expressing large numbers of normal human insulin receptors (HIRc-B cells),
      insulin (greater than or equal to 0.7 nM) stimulated the rapid accumulation of
      mRNAs for both genes. This response was blunted, but not lost, in cells
      expressing large numbers of human insulin receptors missing 43 amino acids at the
      carboxyl terminus of the beta-subunit. In contrast, the insulin response was
      completely absent in cells expressing large numbers of receptors that contained a
      mutation at the ATP-binding site that destroyed intrinsic protein tyrosine kinase
      activity (A/K 1018-B cells). This mutation also suppressed the modest
      transcriptional response to insulin that occurred in the parental Rat 1 cells.
      The transcriptional response to serum was normal in the A/K 1018-B cells, even
      after protein kinase C depletion; however, the response to insulin-like growth
      factor I was essentially lost. These studies suggest that overexpression of a
      kinase-deficient insulin receptor can suppress the transcriptional response to
      both insulin and insulin-like growth factor I that is ordinarily transduced
      through endogenous insulin and insulin-like growth factor I receptors,
      respectively. Competition for shared substrates of these related receptor kinases
      is a potential mechanism for this effect.

PMID- 1985911
TI  - Cloning of murine tissue factor and regulation of gene expression by transforming
      growth factor type beta 1.
AB  - We have cloned a serum- and cycloheximide-inducible mRNA from AKR-2B murine
      fibroblasts which encodes a protein with significant sequence similarity to human
      tissue factor, a cellular initiator of the blood coagulation cascade. Information
      derived from this clone was used to establish the presence of a virtually
      identical sequence in mouse brain. Most importantly, cDNA-directed expression in
      a quail fibroblast cell line produced high levels of tissue factor procoagulant
      activity, confirming the identity of this protein as murine tissue factor.
      Additional studies demonstrate that transforming growth factor type beta 1
      stimulates tissue factor gene transcription and is a potent inducer of tissue
      factor procoagulant activity in fibroblasts. Other tested mitogens such as
      platelet-derived growth factor, epidermal growth factor, and insulin were weak
      inducers. These results may reflect a role for transforming growth factor beta 1
      in the maintenance of hemostasis or, alternatively, a role for tissue factor in
      cellular functions unrelated to blood coagulation.

PMID- 1985912
TI  - Human hexokinase type I microheterogeneity is due to different amino-terminal
      sequences.
AB  - Human placenta hexokinase type I was previously shown to be present in two
      subtypes with similar isoelectric points but different molecular masses of 112
      and 103 kDa, respectively. In order to exclude that these subtypes arise by
      artifact(s) occurring during the protein purification, we have developed a single
      step immunoaffinity chromatography for the isolation of microgram quantities of
      hexokinase. The results obtained confirmed the presence of both hexokinase
      subtypes in human placenta. By Northern blot analysis a single mRNA species that
      hybridized with a hexokinase-I cDNA was found to be present in human placenta.
      Furthermore, in vitro translation of placenta mRNA in a rabbit reticulocyte
      lysate followed by hexokinase immunoprecipitation and sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and fluorography showed that only one
      hexokinase with apparent molecular mass of about 112 kDa is expressed in this
      tissue and suggests a post-translational modification as a probable cause of
      hexokinase I microheterogeneity. To further investigate this point we have
      purified the high and low Mr hexokinase and determined their NH2-terminal
      sequences. The results obtained show that when compared with the amino acid
      sequence deduced from a cDNA the high Mr hexokinase starts at amino acid 11 while
      the low Mr hexokinase starts at amino acid 103. Since the first 10 amino acids
      are involved in the binding of hexokinase to mitochondrial porin these data
      provide an explanation both for the inability of these hexokinases to bind to
      mitochondria and for their differences in Mr.

PMID- 1985913
TI  - Transcriptional activation and nuclear targeting signals of the human androgen
      receptor.
AB  - The androgen receptor (AR) is a signal-transducing protein required for sexual
      differentiation, development, and expression of the male phenotype. A series of
      human AR deletion mutants were created either by site-directed mutagenesis using
      restriction enzyme digestion, the polymerase chain reaction, or, for a series of
      unidirectional NH2-terminal deletions, exonuclease III digestion. Receptor
      mutants were expressed in monkey kidney COS cells as truncated AR proteins
      between 20 and 107 kDa as revealed on immunoblots, where wild type AR was a
      doublet of 114 and 108 kDa. Subcellular localization by immunocytochemical
      staining demonstrated androgen-dependent nuclear uptake of AR from a perinuclear
      region of the cytoplasm. A nuclear targeting signal similar in sequence and
      position to the glucocorticoid receptor and homologous to the SV40 large T
      antigen was required for androgen-induced nuclear uptake of wild type AR. AR
      mutants lacking the NH2-terminal and/or steroid binding domains were
      constitutively nuclear with reduced transcriptional activity. Transcriptional
      activation by wild type AR was androgen-dependent in cotransfection studies of
      CV1 cells using the chloramphenicol acetyltransferase reporter gene linked to the
      mouse mammary tumor virus promoter. Deletion mutagenesis revealed within the NH2
      terminal region a domain required for full transcriptional activity and within
      the steroid binding domain, an inhibitory function, deletion of which yielded a
      constitutively active receptor. Inhibition of wild type AR by coexpression with
      an inactive NH2-terminal fragment suggested competition for nuclear factors
      required for transcriptional regulation. These studies demonstrate a concerted
      interplay among the domains of the AR protein in regulating gene transcription.

PMID- 1985914
TI  - Positive modulation of hemoglobin, heme, and transferrin receptor synthesis by
      murine interferon-alpha and -beta in differentiating Friend cells. Pivotal role
      of heme synthesis.
AB  - Administration of highly purified preparations of murine interferon (IFN)-alpha
      1, -alpha 4, -alpha 6, or -beta to Friend leukemia cells induced to differentiate
      by dimethyl sulfoxide leads to a 100% increase of benzidine-positive (B+) cells.
      Different efficiencies for the two IFN species have been observed; a 10-fold
      higher dose of IFN-alpha is needed for stimulation of hemoglobin production and
      inhibition of cell growth as compared with IFN-beta. Both species of IFN induce a
      substantial increase in heme, hemoglobin, and transferrin receptor levels. In
      vitro run-on transcription assays indicate that IFN-beta moderately stimulates
      transcription of the alpha-globin gene but not the transferrin receptor gene. It
      is postulated that IFN induces the enhancing effect on differentiation via a
      marked increase of heme synthesis and number of transferrin receptors, which in
      turn leads to an enhancement of globin chain synthesis. In this regard, the
      negative feedback reported in a variety of other cell types for the regulation of
      transferrin receptor expression by heme does not seem to be operative in maturing
      Friend erythroleukemia cells, which present evidence for a positive mechanism.

PMID- 1985915
TI  - An estrogen-responsive element mediates the transcriptional regulation of
      calbindin D-9K gene in rat uterus.
AB  - The rat calbindin (molecular mass 9 kDa) gene sequence revealed the presence of
      an imperfect palindromic estrogen-responsive-like element (ERE) located at
      position +51 from the transcriptional initiation site. This element has the
      sequence AGGTCAGGGTGATCT which differs by one nucleotide from the vitellogenin
      ERE palindromic sequence AGGTCACTGTGACCT. The activity of this element to induce
      transcription in response to estrogen and the ability to bind estrogen receptor
      was investigated. This sequence confers estrogen-dependent transcriptional
      activity when cloned upstream from the tkp-CAT construct in pBLCAT2 plasmid and
      transfected into T47D cells, similar to the vitellogenin gene ERE activity but to
      a lesser extent. This element binds to the estrogen receptor in vitro as assessed
      by gel retardation assay similar to the vitellogenin gene ERE. No such binding
      was detected when a mutant sequence AGATCACTGTGATCT was used. The specificity of
      the complex was confirmed using polyclonal antibodies, ER712 raised against the
      estrogen receptor. Furthermore, competition assays showed that both sequences
      were able to compete for binding to the estrogen receptor. The in vivo
      transcriptional regulation of the calbindin D-9K gene by estrogen was also
      investigated in the rat. Female animals maintained on a vitamin D-sufficient or a
      vitamin D-deficient diet were ovariectomized, housed for 3 weeks, and then
      injected with 17 beta-estradiol (0.5 micrograms/kg body weight/day). Slot blot
      analysis of total RNA showed a marked increased in calbindin D-9K mRNA levels in
      the uterus but not in the intestine by 26 and 50 h post-injection. These results
      demonstrate that the calbindin D-9K gene is transcriptionally regulated by
      estrogen in the uterus mediated by an estrogen-responsive element identified in
      the gene.

PMID- 1985916
TI  - Sequence-specific transcriptional antirepression of the Drosophila Kruppel gene
      by the GAGA factor.
AB  - We have analyzed the proximal promoter of the Drosophila Kruppel (Kr) gene. A 44
      base pair fragment containing the RNA start sites contains significant promoter
      activity, and this minimal promoter is flanked both upstream and downstream by
      binding sites for the GAGA factor. The GAGA factor is the predominant sequence
      specific DNA binding factor that interacts with the Kr promoter region, and the
      purified protein activates Kr transcription in vitro. However, strong
      transcriptional activation of Kr as well as of Ultrabithorax, another GAGA factor
      responsive gene, requires the presence of a DNA binding transcriptional
      repressor. The GAGA factor is able to relieve this repression in a binding site
      dependent manner, and, thus, these data suggest that the GAGA factor functions as
      an antirepressor, rather than an activator, of the Kr gene.

PMID- 1985917
TI  - Characterization of rat 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4
      isomerase cDNAs and differential tissue-specific expression of the corresponding
      mRNAs in steroidogenic and peripheral tissues.
AB  - The conversion of 3 beta-hydroxy-5-ene steroids by the enzyme complex 3 beta
      hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase (3 beta-HSD) is an
      essential step in the biosynthesis of all classes of hormonal steroids. We report
      the characterization of two types of cDNA clones encoding rat 3 beta-HSD isolated
      from a rat ovary lambda gt11 cDNA library with a human 3 beta-HSD cDNA probe.
      Both type I and type II cDNAs encode proteins of 372 amino acids having 94%
      homology. Transient expression of the type I and the type II 3 beta-HSD cDNAs in
      HeLa human cervical carcinoma cells reveals that both proteins possess 3 beta
      hydroxysteroid dehydrogenase as well as delta 5-delta 4 isomerase activities for
      both delta 5-pregnene and delta 5-androstene precursors, although the type I 3
      beta-HSD protein is more active than the type II. RNA blot analysis using type I
      3 beta-HSD cDNA identifies major mRNA transcripts of 1.7 kilobase in rat ovary,
      testis, and adrenal poly(A)+ RNA. RNase protection assay using type I- and type
      II-specific cRNA probes revealed the existence of the two corresponding mRNAs in
      male and female rat adrenals and gonads as well as in female adipose tissue while
      only type I mRNA is present in male and female kidney. Moreover, in situ
      hybridization performed using type-specific labeled 24-mer oligonucleotides
      confirms that type I is the major mRNA species in the ovary and further indicates
      that both mRNA species have a similar cellular distribution in the ovarian tissue
      with the highest level of expression found in corpora lutea. Immunoblot analysis
      using polyclonal antibodies raised against purified human placental 3 beta-HSD
      identified a single 42-kDa band in rat ovary, testis, and adrenal, which agrees
      with the calculated molecular masses of 41,911 and 42,150 daltons for the type I
      and II proteins, respectively. Determination of 3 beta-HSD enzymatic activity
      using [14C]pregnenolone and [14C]dehydroepiandrosterone as substrates shows that
      3 beta-HSD activity is present not only in the gonads and adrenals of animals of
      both sexes, but also in many peripheral tissues including adipose tissue, mammary
      gland, kidney, liver, prostate, seminal vesicle, uterus, skin, brain, heart,
      thymus, pancreas, lung, and spleen. The present data indicate the existence of
      two mRNAs encoding rat 3 beta-HSD and their differential tissular distribution in
      both steroidogenic and peripheral tissues.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1985918
TI  - Proliferative action of erythropoietin is associated with rapid protein tyrosine
      phosphorylation in responsive B6SUt.EP cells.
AB  - Erythropoietin is a prime regulator of the growth and terminal differentiation of
      erythroid blood cells. However, little is understood concerning its molecular
      mechanism of action. Presently it is shown in the responsive, factor-dependent
      murine cell line B6SUt.EP that erythropoietin induces the tyrosine
      phosphorylation of six plasma membrane-associated proteins in a time- and
      concentration-dependent fashion (i.e. phosphoproteins PY153, PY140, PY100, PY93,
      PY74, and PY54). Among these, PY153 was prominent. For all proteins, maximal
      levels of phosphorylation were induced within 3-7 min at low factor
      concentrations (100-500 pM). These findings establish tyrosine kinase activation
      as a novel candidate pathway of erythropoietin-induced proliferation. In
      addition, the tyrosine phosphorylation of six proteins with identical Mr, as well
      as a Mr 104,000 protein, was induced in B6SUt.EP cells by interleukin 3. In
      contrast, no induced tyrosine phosphorylation was detectable in the
      erythropoietin-responsive, leukemic erythroid cell line. Rauscher Red 1, yet
      proteins of Mr 153,000 and 54,000 were shown to be phosphorylated constitutively
      at relative levels greater than those observed in B6SUt.EP cells. A possible role
      for these phosphoproteins in hematopoietic cell transformation is considered.

PMID- 1985919
TI  - Domain structure of synaptotagmin (p65)
AB  - Synaptotagmin (p65) is an abundant and evolutionarily conserved protein of
      synaptic vesicles that contains two copies of an internal repeat homologous to
      the regulatory region of protein kinase C. In the current study, we have
      investigated the biochemical properties of synaptotagmin, demonstrating that it
      contains five protein domains: an intravesicular amino-terminal domain that is
      glycosylated but lacks a cleavable signal sequence; a single transmembrane
      region; a sequence separating the transmembrane region from the two repeats
      homologous to protein kinase C; the two protein kinase C-homologous repeats; and
      a conserved carboxyl-terminal sequence following the two repeats homologous to
      protein kinase C. Sucrose density gradient centrifugations and gel
      electrophoresis indicate that synaptotagmin monomers associate into dimers and
      are part of a larger molecular weight complex. A sequence predicted to form an
      amphipathic alpha-helix that may cause the stable dimerization of synaptotagmin
      is found in its third domain between the transmembrane region and the protein
      kinase C-homologous repeats. Synaptotagmin contains a single hypersensitive
      proteolytic site that is located immediately amino-terminal to the amphipathic
      alpha-helix, suggesting that synaptotagmin contains a particularly exposed region
      as the peptide backbone emerges from the dimer. Finally, subcellular
      fractionation and antibody bead purification demonstrate that synaptotagmin co
      purifies with synaptophysin and other synaptic vesicle markers in brain. However,
      in the adrenal medulla, synaptotagmin was found in both synaptophysin-containing
      microvesicles and in chromaffin granules that are devoid of synaptophysin,
      suggesting a shared role for synaptotagmin in the exocytosis of small synaptic
      vesicles and large dense core catecholaminergic vesicles.

PMID- 1985920
TI  - Cloning, expression, and nucleotide sequence of rat liver sterol carrier protein
      2 cDNAs.
AB  - The structure and expression of rat sterol carrier protein 2 (SCP2) were studied
      by cloning and sequencing SCP2 cDNAs and by hybridizing the SCP2 cDNA to RNA from
      a variety of rat tissues. Initial screening of a rat liver cDNA library with an
      oligonucleotide probe derived from the rat SCP2 protein sequence revealed an 825
      base pair cDNA clone coding for the complete SCP2 protein sequence. Our results
      suggest that rat liver SCP2 is 143 amino acid residues long, including a 20-amino
      acid residue prepeptide (pre-SCP2). Using the rat SCP2 cDNA as a probe for
      Northern blot hybridization analyses under high stringency conditions with rat
      liver poly(A) RNA, four mRNA species differing in their sizes and levels of
      expression are detected. The lengths of the corresponding mRNAs are 0.8, 1.4,
      2.1, and 2.7 kilobases (kb), respectively. In all other tissues analyzed mRNAs
      hybridizing to the SCP2 cDNA probe were detected in levels much lower than in the
      liver. In these tissues the vast majority of the expressed SCP2 mRNAs consists of
      the 0.8-kb mRNA. Results from Southern blotting hybridization analyses with rat
      genomic DNA suggest that the four different mRNA species are products of a single
      gene. Extensive screening of rat liver cDNA libraries using rat liver SCP2 cDNA
      probes led to the isolation of 10 additional clones, all of them containing cDNA
      insertions longer than 0.8 kb. Restriction mapping and nucleotide sequencing
      analyses of these cDNAs indicate that eight extend upstream of the SCP2 cDNA, and
      two extend 5' as well as 3'. Translation of the sequence extending most upstream
      suggests that this cDNA is a nearly full-length cDNA coding for a protein of 547
      amino acids (SCP chi). SCP chi contains a 404-amino acid amino-terminal extension
      as compared with pre-SCP2 whereas its carboxyl-terminal part is identical with
      pre-SCP2. Sequencing of the 3' extension cDNAs suggests that polyadenylation had
      occurred 651 nucleotides downstream as compared with the remaining cDNAs. A probe
      from this region hybridizes to the 1.4- and 2.7-kb mRNAs. From our data we
      conclude that the 1.4- and 2.7-kb mRNA species are generated by alternative
      polyadenylation of the 0.8- and 2.1-kb mRNAs, respectively. In contrast, the 2.1-
      and 2.7-kb mRNAs contain an approximately 1300-nucleotide extension upstream of
      the 0.8- and 1.4-kb mRNAs, suggesting differential splicing of the primary SCP2
      gene transcript leading to expression of pre-SCP2 and SCP chi from a single gene.

PMID- 1985921
TI  - Specific contacts between the bacteriophage T3, T7, and SP6 RNA polymerases and
      their promoters.
AB  - The specificity and structural simplicity of the bacteriophage T3, T7, and SP6
      RNA polymerases make these enzymes particularly well suited for studies of
      polymerase-promoter interactions. To understand the initial recognition process
      between the enzyme and its promoters, DNA fragments that carry phage promoters
      were chemically modified by three different methods: base methylation, phosphate
      ethylation, and base removal. The positions at which these modifications
      prevented or enhanced binding by the RNA polymerases were then determined. The
      results indicate that specific contacts within the major groove of the promoter
      between positions-5 and -12 are important for phage polymerase binding. Removal
      of individual bases from either strand of the initiation region (-5 to +3)
      resulted in enhanced binding of the polymerase, suggesting that disruption of the
      helix in this region may play a role in stabilization of the polymerase-promoter
      complexes.

PMID- 1985922
TI  - Three-dimensional structure of a sarcoplasmic calcium-binding protein from Nereis
      diversicolor.
AB  - The three-dimensional structure of a sarcoplasmic Ca2(+)-binding protein from the
      sandworm Nereis diversicolor has been determined at 3.0 A resolution using
      multiple isomorphous replacement techniques. The NH2-terminal half of the
      molecule contains one variant Ca2(+)-binding domain with a novel helix-loop-helix
      conformation and one Ca2(+)-binding domain that is no longer functional because
      of amino acid changes. The overall conformation of this pair of domains is
      different from any previously described Ca2(+)-binding protein. The COOH-terminal
      half of the protein contains two Ca2(+)-binding domains with the usual helix-loop
      helix configuration and is similar to calmodulin and troponin C. Unlike
      calmodulin or troponin C, there is no exposed alpha-helix connecting the two
      halves of the molecule, so the overall structure is much more compact.

PMID- 1985923
TI  - Assembly properties of tubulin after carboxyl group modification.
AB  - By chemically modifying carboxyl groups we have investigated the role of the
      highly acidic COOH-terminal domains of alpha- and beta-tubulin in regulating
      microtubule assembly. Using a carbodiimide-promoted amidation reaction, as many
      as 25 carboxyl groups were modified by the addition of 1-ethyl-3-(3
      dimethylaminopropyl)carbodiimide and an amine nucleophile, [14C] glycine ethyl
      ester or [3H]methylamine, to assembled microtubules. Modification occurred
      primarily in the carboxyl-terminal region as demonstrated by limited proteolysis
      of modified tubulin by trypsin, chymotrypsin, subtilisin, and carboxypeptidase Y.
      Modified tubulin polymerized into microtubules with a critical concentration that
      was 15% of that for unmodified tubulin. Assembly of modified tubulin and
      microtubules formed from modified tubulin were less sensitive to Ca2+ and high
      ionic strength. Ca2+ binding studies under low ionic strength conditions
      indicated that modified tubulin does not contain the high affinity Ca2+ binding
      site. While assembly of unmodified tubulin was stimulated by Mg2+ up to 10 mM,
      assembly of the modified protein was inhibited by concentrations greater than 1
      mM. When 24 residues were modified, polymerization was no longer stimulated by
      microtubule-associated proteins (MAPs) or polylysine and incorporation of high
      molecular weight MAPs into the polymers was reduced by about 70% compared to
      unmodified tubulin. These studies demonstrate that chemical modification of
      carboxyl groups in tubulin, most of which are localized in the COOH-terminal
      region, leads to an enhanced ability to polymerize and a decrease in interaction
      with MAPs and other positively charged species.

PMID- 1985924
TI  - Two dissociable subunits of yeast RNA polymerase II stimulate the initiation of
      transcription at a promoter in vitro.
AB  - RNA polymerase II lacking the fourth and seventh largest subunits (pol II delta
      4/7) was purified from Saccharomyces cerevisiae strain rpb-4, in which the gene
      for the fourth largest subunit is deleted. pol II delta 4/7 was indistinguishable
      from wild-type pol II (holoenzyme) in promoter-independent initiation/chain
      elongation activity (400-800 nmol of nucleotide incorporated/10 min/mg of protein
      at 22 degrees C), in rate of chain elongation (20-25 nucleotides/s), and in the
      recognition of pause sites in the DNA template. In contrast to pol II holoenzyme,
      pol II delta 4/7 was inactive in promoter-directed initiation of transcription in
      vitro. The addition of an equimolar complex of the fourth and seventh largest
      subunits, purified from pol II holoenzyme by ion-exchange chromatography in the
      presence of urea, restored promoter-directed initiation activity to pol II delta
      4/7. The transcriptional activator protein Gal4-VP16 could also elicit promoter
      directed initiation by pol II delta 4/7 from a promoter with a Gal4 binding site.
      Complementation was observed between extracts of strain rpb-4, lacking the fourth
      largest subunit, and strain Y260-1, with a defect in the largest subunit. These
      extracts were individually inactive, but a mixture would support promoter
      directed initiation. The fourth and seventh largest subunits may, therefore,
      shuttle between polymerase molecules.

PMID- 1985925
TI  - High affinity divalent cation exchange on actin. Association rate measurements
      support the simple competitive model.
AB  - Each actin molecule has one high affinity site which binds a divalent cation. It
      has been proposed that an isomerization of the actin molecule is involved in
      divalent cation exchange at this site ("isomerization model," Frieden, C. (1982)
      J. Biol. Chem. 257, 2882-2886); we have maintained that exchange is by a simple
      competitive mechanism (Estes, J. E., Selden, L. A., and Gershman, L. C. (1987) J.
      Biol. Chem. 262, 4952-4957). Here, using fluorescent-labeled actin, we measure
      the apparent rate constant for exchange (kapp) as a function of the ratio of free
      Ca2+ and Mg2+ concentrations, ([Ca]/[Mg]), and show that both models are
      consistent with the data. The major parameter controlling this relationship in
      the simple competitive exchange model, the ratio of the association rate
      constants for Ca2+ and Mg2+ to actin (kCa/kMg), is found to have a value of about
      90. We have verified this parameter by direct measurements of kCa and kMg,
      finding that kCa = 1.9 x 10(7) M-1 s-1 and kMg = 2.3 x 10(5) M-1 s-1, consistent
      with the characteristics of the Ca2+ and Mg2+ aquo ions. The corresponding
      parameter derived from the isomerization model is not verifiable. We conclude
      that high affinity divalent cation exchange on actin proceeds by a simple
      competitive mechanism.

PMID- 1985926
TI  - Characterization of the carbohydrate binding specificity of the
      leukoagglutinating lectin from Maackia amurensis. Comparison with other sialic
      acid-specific lectins.
AB  - The sialic acid-specific leukoagglutinating lectin from the seeds of Maackia
      amurensis (MAL) has been studied by the techniques of quantitative precipitin
      formation, hapten inhibition of precipitation, hapten inhibition using an enzyme
      linked immunosorbent assay, and lectin affinity chromatography. The ability of
      the immobilized lectin to fractionate oligosaccharides based on their content of
      sialic acid has also been investigated. Our results indicate that MAL reacts with
      greatest affinity with the trisaccharide sequence Neu5Ac/Gc alpha 2,3Gal beta
      1,4GlcNAc/Glc. The lectin requires three intact sugar units for binding and does
      not interact when the beta 1,4-linkage is replaced by a beta 1,3-linkage nor when
      the "reducing sugar" of the trisaccharide is reduced. Results from enzyme-linked
      immunosorbent assays show that an N-acetyllactosamine repeating sequence is not
      required; however, the N-acetyllactosamine repeating sequence does appear to
      enhance the binding of MAL to a series of glycolipids. In addition, the sialic
      acid may be substituted with either N-acetyl or N-glycolyl groups without
      reduction in binding. The C-8 and C-9 hydroxyl groups of sialic acid do not play
      a role in binding as shown by the strong reaction of periodate-treated
      glycoproteins. Comparison of the specificity of the three sialic acid-binding
      lectins indicates that Limax flavus agglutinin binds to Neu5Ac in any linkage and
      in any position in a glycoconjugate, Sambucus nigra lectin requires a
      disaccharide of the structure Neu5Ac alpha 2,6Gal/GalNAc, and MAL has a binding
      site complimentary to the trisaccharide Neu5Ac alpha 2,3Gal beta 1,4GlcNAc/Glc,
      to which sialic acid contributes less to the total binding affinity than for
      either S. nigra lectin or L. flavus agglutinin.

PMID- 1985927
TI  - Human cytotoxic lymphocyte granzyme B. Its purification from granules and the
      characterization of substrate and inhibitor specificity.
AB  - Granzyme B has been purified to homogeneity from the granules of a human
      cytolytic lymphocyte line, Q31, in an enzymatically active form by a three-step
      procedure. Q31 granzyme B hydrolyzed Na-t-butyloxycarbonyl-L-alanyl-L-alanyl-L
      aspartyl (Boc-Ala-Ala-Asp) thiobenzyl ester with a kcat of 11 +/- 5 mol/s/mol
      enzyme and catalytic efficiency kcat/Km of 76,000 +/- 44,000 M-1 s-1. The
      hydrolysis of Boc-Ala-Ala-Asp thiobenzyl ester by crude Q31 Percoll fractions
      paralleled the tryptase activity for granule-containing fractions, which showed
      that granzyme B was associated with granules. When chromatographed on Sephacryl S
      300, Q31 granzyme B eluted in two broad bands corresponding to dimer and monomer,
      both of which electrophoresed at 35 kDa in reducing NaDodSo4 polyacrylamide, and
      both of which showed a lag phase in assays. The lag phase in assays could be
      extended with 0.03 mM pepstatin. Upon elution from ion-exchange chromatography
      Q31 granzyme B electrophoresed at 32 kDa in reducing NaDodSO4 polyacrylamide and
      did not have a lag phase in assays. The amino-terminal sequence of the 32-kDa Q31
      granzyme B was identical to four other human cytotoxic T-lymphocyte granzymes B
      in 18 of 18 positions sequenced. Purified Q31 granzyme B had a preference for
      substrates with Glu or Asp as the residue amino-terminal to the scissile bond;
      little or no activity was noted with oligopeptide substrates for trypsin-like,
      chymotrypsin-like, and elastase-like proteases. Human plasma alpha 1-protease
      inhibitor, human plasma alpha 2-protease macroglobulin, soybean and lima-bean
      trypsin inhibitors, bovine aprotinin, phosphoramidon, and chymostatin inhibited
      Q31 granzyme B. The inhibition by alpha 1-protease inhibitor was rapid enough to
      be of physiological significance.

PMID- 1985928
TI  - Amino acid sequences of the two subunits of a phospholipase A2 inhibitor from the
      blood plasma of Trimeresurus flavoviridis. Sequence homologies with pulmonary
      surfactant apoprotein and animal lectins.
AB  - Phospholipase A2 inhibitor (PLI), purified from the blood plasma of the Habu
      snake (Trimeresurus flavoviridis), was separated into two distinct subunits, PLI
      A and PLI-B. These subunits were shown to be glycoproteins with molecular weights
      of around 21,000-22,000. When they were deglycosylated chemically with
      trifluoromethanesulfonic acid, the molecular weights were found to be 17,000.
      Their amino acid sequences were determined by alignment of peptides obtained by
      lysyl endopeptidase digestion and Staphylococcus aureus V8 protease digestion.
      PLI-A and PLI-B were each composed of 147 amino acid residues with one residue,
      Asn103, being for N-linked glycosylation, and the molecular weights of their
      protein portions were calculated to be 16,368 and 16,408, respectively. Each
      subunit contained four cysteine residues, all of which exist in disulfide
      linkages (Cys64-Cys141 and Cys119-Cys133). The sequences of PLI-A and PLI-B
      showed 89.9% homology to each other. When the sequences were compared with those
      of lipocortins, no significant homologies were detected. But the sequences were
      significantly homologous to those of COOH-terminal carbohydrate recognition
      portions of pulmonary surfactant apoprotein and animal lectins.

PMID- 1985929
TI  - Functional characterization and receptor binding studies of the malic enzyme
      thyroid hormone response element.
AB  - We previously showed that the 5'-flanking region of the malic enzyme (ME) gene
      contains a cis-regulatory element (-281 to -261) that binds thyroid hormone
      receptors and confers triiodothyronine (T3) inducibility of transcription to the
      ME promoter (Petty, K.J., Desvergne, B., Mitsuhashi, T., and Nikodem, V. M.
      (1990) J. Biol. Chem. 265, 7395-7400). In this report, we have used deletion and
      mutation analyses of the ME thyroid hormone response element (TRE) to evaluate
      the roles of several subregions of TRE in T3 binding and transactivation. ME TRE
      was shown to act as an enhancer conferring T3 responsiveness to a heterologous
      promoter thymidine kinase. Although T3 treatment induced the promoter activity,
      the absence of hormone resulted in repression as measured by the level of
      chloramphenicol acetyltransferase expression in the NIH 3T3 transient expression
      system in the presence of overexpressed receptor. The degree of repression was
      similar to the degree of T3 induction observed for the same TRE mutants. Mutation
      and deletion analyses indicated that the functional TRE is comprised of discrete
      regions that are not contiguous, with a dominant role of a cluster of G residues
      and an AGGACA sequence. Both functions, induction and repression of
      transcription, correlated with receptor binding to the ME TRE as determined by
      competition binding assays using wild type and mutated TRE as competitors.

PMID- 1985930
TI  - Identification of a peptide inhibitor of the cardiac sarcolemmal Na(+)-Ca2+
      exchanger.
AB  - The deduced amino acid sequence of the cardiac sarcolemmal Na(+)-Ca2+ exchanger
      has a region which could represent a calmodulin binding site. As calmodulin
      binding regions of proteins often have an autoinhibitory role, a synthetic
      peptide with this sequence was tested for functional effects on Na(+)-Ca2+
      exchange activity. The peptide inhibits the Na(+)-dependent Ca2+ uptake (KI
      approximately 1.5 microM) and the Nao(+)-dependent Ca2+ efflux of sarcolemmal
      vesicles in a noncompetitive manner with respect to both Na+ and Ca2+. The
      peptide is also a potent inhibitor (KI approximately 0.1 microM) of the Na(+)
      Ca2+ exchange current of excised sarcolemmal patches. The binding site for the
      peptide on the exchanger is on the cytoplasmic surface of the membrane. The
      exchanger inhibitory peptide binds calmodulin with a moderately high affinity.
      From the characteristics of the inhibition of the exchange of sarcolemmal
      vesicles, we deduce that only inside-out sarcolemmal vesicles participate in the
      usual Na(+)-Ca2+ exchange assay. This contrasts with the common assumption that
      both inside-out and right-side-out vesicles exhibit exchange activity.

PMID- 1985931
TI  - Amino acid control of proteolysis in perfused livers of synchronously fed rats.
      Mechanism and specificity of alanine co-regulation.
AB  - The primary control of autophagically mediated proteolysis in perfused rat liver
      is carried out via two alternate mechanisms in response to specific regulatory
      amino acids. One (L) elicits direct inhibition at low and high plasma levels, but
      requires a co-regulatory amino acid to express inhibition at normal
      concentrations. The second (H) is ineffective at normal levels and below, but
      active at higher concentrations. Because regulation is subject to unpredictable
      variability with ad libitum feeding, we have utilized rats synchronously fed 4 h
      day-1 to stabilize responses. Proteolytic control is seen to evolve in stages: H
      appears 12 h after the start of feeding; by 18 h L emerges, alternating with H in
      a statistically predictable way; with omission of the 24-h feeding, H disappears
      and L remains constant through 42 h. In both 18- and 42-h rats, alanine,
      glutamate, and aspartate exhibit similar inhibitory activity when added singly to
      the regulatory group at normal plasma concentrations. However, since alanine, but
      not glutamate or aspartate, evokes proteolytic acceleration when it is deleted
      from a full plasma mixture, alanine appears to be the sole co-regulator. Alanine
      yields co-regulatory effects with normal plasma leucine (0.2 mM) in 18- and 42-h
      animals and interacts synergistically with 0.8 mM leucine in 42-h but not in 18-h
      rats where leucine alone inhibits strongly. Because the inactivation of alanine
      amino-transferase by aminooxyacetate (determined from the conversion of
      [14C]alanine to glucose) does not alter the co-regulatory and synergistic effects
      of alanine, regulation by alanine must be mediated from a site of recognition
      before transamination.

PMID- 1985932
TI  - Occurrence of sulfate in an asparagine-linked complex oligosaccharide of chicken
      adipose lipoprotein lipase.
AB  - After adipocytes were labeled with Na2[35SO4], immunoadsorbed with immobilized
      antilipoprotein lipase, and subjected to sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis (SDS-PAGE) and fluorography, a labeled band was identified at
      59,700 daltons, the molecular mass of chicken lipoprotein lipase (LPL). Excess
      unlabeled LPL prevented the immunoadsorption of this labeled species, hence the
      labeled species was determined to be LPL. Digestion of LPL with endo-beta-N
      acetylglucosaminidase H (Endo H) caused a shift in mobility of LPL in SDS-PAGE
      with no loss of radioactivity, whereas digestion with glycopeptidase F resulted
      in removal of 99% of the radioactivity. Adipocytes cultured with Trans35S-label
      and tunicamycin produced an LPL species of 52,000 daltons, but tunicamycin
      abolished the incorporation of 35SO4 into LPL. This established that 35SO4 was
      incorporated into an N-linked oligosaccharide of LPL. Endo H digestion of pulse
      chase labeled LPL revealed the presence of two complex and one high mannose-type
      N-linked oligosaccharides. A single 35SO4-labeled tryptic peptide was isolated by
      reverse phase chromatography. The amino acid sequence of the peptide established
      that the 35SO4 oligosaccharide is conjugated at Asn-45. Behavior of the 35SO4
      labeled oligosaccharide on concanavalin A-agarose, sequential exoglycosidase
      digestion, and chemical analysis of the 35SO4 oligosaccharide confirms that this
      moiety is of the complex type. Sequential exoglycosidase digestion, thin layer
      chromatography of the released monosaccharides, and the use of glycosylation
      inhibitors established that the sulfated sugar is a core N-acetylglucosamine
      (GlcNAc). The data show that chicken LPL contains two complex and one high
      mannose N-linked oligosaccharides and that 35SO4 is incorporated into LPL on a
      GlcNAc residue of a complex oligosaccharide located at Asn-45.

PMID- 1985933
TI  - Primary sequence of the glucanase gene from Oerskovia xanthineolytica. Expression
      and purification of the enzyme from Escherichia coli.
AB  - A 2.7-kilobase fragment of DNA from Oerskovia xanthineolytica containing the gene
      for a beta-1,3-glucanase has been isolated and its complete nucleotide sequence
      determined. The sequence was found to contain two large open reading frames.
      Purification of the mature native enzyme and subsequent amino-terminal sequencing
      defined the glucanase gene in one reading frame which potentially encodes a
      protein of 548 amino acids. We have expressed this glucanase gene in Escherichia
      coli under control of the lacUV5 promoter and found the product to be secreted
      into the periplasm as a mature enzyme of about the same molecular weight as that
      of the native protein. The recombinant enzyme was purified to near homogeneity by
      a single step of high performance liquid chromatography. The ability of the
      recombinant enzyme to digest beta-glucan substrates and to lyse viable yeast
      cells was found to be indistinguishable from that of the native protein. Deletion
      of the cysteine-rich carboxyl-terminal 117 amino acids of the enzyme, which also
      contain two duplicated segments, abolished the lytic activity but did not
      significantly affect the glucanase function of the protein. The possible
      involvement of this domain in interaction with the yeast cell wall is discussed.

PMID- 1985934
TI  - Structural and immunological comparison of indigenous human O6-methylguanine-DNA
      methyltransferase with that encoded by a cloned cDNA.
AB  - O6-Methylguanine-DNA methyltransferase, a ubiquitous and unusual DNA repair
      protein, eliminates mutagenic and cytotoxic O6-alkylguanine from DNA by
      transferring the alkyl group to one of its cysteine residues in a second-order
      suicide reaction. This 22-kDa protein was immunoaffinity-purified to homogeneity
      from cultured human lymphoblasts (CEM-CCRF line) and compared with the O6
      methylguanine-DNA methyltransferase purified to homogeneity from Escherichia coli
      expressing a cloned human cDNA. The cellular and recombinant proteins were
      identical in size, as determined by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis of intact molecules and their peptides. Immunoprobing of Western
      blots with three monoclonal antibodies specific for human cellular O6
      methylguanine-DNA methyltransferase further indicated identity of the two
      proteins. The amino acid sequence of the cellular protein was experimentally
      determined for 87 out of a total of 207 residues and was found to be identical to
      that deduced from the cDNA sequence. A unique cysteine residue at position 145
      was identified as the methyl acceptor site by autoradiographic analysis of
      peptides and sequence analysis of 3H-methylated O6-methylguanine-DNA
      methyltransferase. These observations establish that the cloned O6-methylguanine
      DNA methyltransferase cDNA encodes the full-length O6-methylguanine-DNA
      methyltransferase polypeptide that is normally present in human cells. Moreover,
      the cellular protein does not appear to be significantly modified by
      posttranslational processes.

PMID- 1985935
TI  - Essential fatty acid deficiency impairs macrophage spreading and adherence. Role
      of arachidonate in cell adhesion.
AB  - Dietary polyunsaturated fatty acid manipulation exerts a strikingly protective
      effect in models of tissue inflammation and injury. A critical element of this
      effect appears to revolve around leukocyte trafficking but underlying mechanisms
      are ill understood. In the current study it was observed that essential fatty
      acid (EFA) deficiency markedly impaired the capacity of resident macrophages to
      spread and adhere. This effect was not a simple function of the alteration of
      membrane fatty acid composition. Elicited EFA-deficient macrophages were equally
      adherent to elicited control cells, despite the fact that they were equally EFA
      deficient relative to resident EFA-deficient cells. With respect to the mechanism
      underlying defective macrophage adherence in EFA deficiency, no change in the
      expression of cell surface adherence molecules (Fc receptor, Mac-1, or LFA-1) was
      noted with the deficiency state. Also, an adherence defect could not be induced
      in normal cells pharmacologically with cyclooxygenase blockade, lipoxygenase
      blockade, or a platelet-activating factor receptor antagonist. In contrast,
      phospholipase inhibition was able to induce a spreading and adherence defect in
      resident macrophages similar to that seen with EFA deficiency. Using several
      phospholipase inhibitors, a correlation between phospholipase inhibition and
      impairment of adherence was observed. Adding back exogenous fatty acids to cells
      after phospholipase inhibition demonstrated that normal adherence was
      reconstituted with arachidonate. This alteration in macrophage spreading and
      adherence with EFA deficiency may be an important component of the anti
      inflammatory effect of dietary polyunsaturated fatty acid manipulation.
      Additionally, these results suggest that arachidonate may be an intracellular
      mediator of leukocyte adherence.

PMID- 1985936
TI  - Regulation of transmembrane signal transduction of insulin-like growth factor II
      by competence type growth factors or viral ras p21.
AB  - In BALB/c 3T3 cells pretreated with platelet-derived growth factor (PDGF) and
      epidermal growth factor (EGF) (primed-competent cells), insulin-like growth
      factors I and II (IGF-I and IGF-II) bind to their own receptors (IGF-IR and IGF
      IIR) and stimulate calcium influx and DNA synthesis by a mechanism involving a 40
      kDa pertussis toxin substrate. In contrast, these IGFs do not act on unprimed
      quiescent cells. In this study, the 40-kDa pertussis toxin substrate was
      identified as Gi-2 alpha using anti-G protein antibodies. We analyzed the quality
      of signal transduction from IGF-II to Gi-2 alpha. There was no difference in the
      amount of Gi-2 alpha between quiescent and primed-competent cells, and both of
      these cells had similar Kd values and numbers of IGF-II-binding sites. Whereas
      IGF-II did not alter pertussis toxin-catalyzed ADP-ribosylation of Gi-2 alpha in
      quiescent cells, IGF-II reduced the pertussis toxin substrate activity by 35-50%
      via the IGF-IIR in primed-competent cells. The action of IGF-II lasted for up to
      3 h when IGF-II was present in the medium, and it disappeared when IGF-II was
      removed. These results suggest that the signaling pathway triggered by IGF-II is
      uncoupled between the IGF-IIR and Gi-2 alpha in quiescent cells and that PDGF and
      EGF restore the IGF-IIR-Gi-2 coupling. This study also indicates that low
      concentrations of IGF-I reduce the pertussis toxin substrate activity of Gi-2
      alpha in primed-competent cells in a time course slower than that of IGF-II, but
      not at all in quiescent cells. However, both of these cells had similar Kd values
      and numbers of IGF-I binding sites. Therefore, the IGF-I signaling pathway may
      also be uncoupled between the IGF-IR and Gi-2 alpha in quiescent cells and
      restored by PDGF and EGF. In BALB/c 3T3 cells transfected with temperature
      sensitive Kirsten sarcoma virus bearing the v-Ki-ras gene (ts cells), a 40-kDa
      pertussis toxin substrate was also identified as Gi-2 alpha. In nonpermissive ts
      cells, IGF-II was without effect on the pertussis toxin substrate activity of Gi
      2 alpha or on calcium influx.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1985937
TI  - Multiple transforming growth factor-beta-inducible elements regulate expression
      of the plasminogen activator inhibitor type-1 gene in Hep G2 cells.
AB  - Regulation of plasminogen activation by plasminogen activator inhibitor type-1
      (PAI-1) is a critical feature of many biological processes. Transforming growth
      factor-beta (TGF-beta) induces PAI-1 mRNA and protein in several types of
      cultured cells, including Hep G2 cells. The present study was performed to define
      mechanisms by which PAI-1 gene expression is regulated by TGF-beta. Nuclear run
      on assays performed on Hep G2 cells stimulated with TGF-beta for 6 h showed a 3.8
      fold increase in PAI-1 gene transcription. TGF-beta increased the half-life of
      PAI-1 mRNA in Hep G2 cells 2.5-fold over control values. To characterize
      transcriptional regulatory mechanisms, we constructed chimeric genes containing
      PAI-1 5'-flanking DNA fused upstream of the bacterial chloramphenicol
      acetyltransferase gene in the vector pSVOCAT and transfected Hep G2 cells.
      Promoter deletion analysis demonstrated that sequences between -791 and -328 and 
      328 to -186 base pairs upstream of the PAI-1 gene cap site contain TGF-beta
      responsive elements that conferred TGF-beta inducibility in an orientation and
      position-independent manner. Further characterization of the larger TGF-beta
      inducible enhancer (-791 to -328) located a TGF-beta-inducible element at
      nucleotides -791 to -546 upstream of the PAI-1 gene cap site. These results
      demonstrate that PAI-1 gene regulation by TGF-beta in Hep G2 cells is mediated
      both at a transcriptional level by two specific inducible elements, as well as by
      post-transcriptional mechanisms.

PMID- 1985938
TI  - Purification and characterization of a new alcohol dehydrogenase from human
      stomach.
AB  - Starch gel electrophoresis of homogenates from human stomach mucosa resolves
      three alcohol dehydrogenase (ADH) forms: the anodic chi-ADH (class III), the
      cathodic gamma-ADH (class I), and a new form of slow cathodic mobility that has
      not been previously characterized. In this work, we describe the purification in
      three chromatographic steps and the physical and kinetic characterization of this
      new human alcohol dehydrogenase, which we have named sigma-ADH. The enzyme
      exhibits the general physicochemical features (Mr, zinc content, subunit Mr,
      cofactor preference) of all mammalian alcohol dehydrogenases. The kinetic studies
      show a high Km value (41 mM) and a high kcat value (280 min-1) for ethanol at pH
      7.5. The Km decreases as the alcohol increases its chain length. The aldehydes
      are better substrates than the corresponding alcohols, with m-nitrobenzaldehyde
      being the best substrate examined. sigma-ADH is strongly inhibited by 4
      methylpyrazole, but with a Ki (10 microM) still higher than that for a class I
      isoenzyme. These properties suggest that sigma-ADH is a class II isoenzyme,
      different from pi-ADH and similar to that previously described by us in rat
      stomach. At the high ethanol concentrations in stomach after drinking, sigma-ADH
      is probably the ADH form with the largest contribution to human gastric ethanol
      metabolism.

PMID- 1985939
TI  - Ca2(+)-dependent regulation of the spectrin/actin interaction by calmodulin and
      protein 4.1.
AB  - The Ca2(+)-dependent regulation of the erythroid membrane cytoskeleton was
      investigated. The low-salt extract of erythroid membranes, which is mainly
      composed of spectrin, protein 4.1, and actin, confers a Ca2+ sensitivity on its
      interaction with F-actin. This Ca2+ sensitivity is fortified by calmodulin and
      antagonized by trifluoperazine, a potent calmodulin inhibitor. Additionally,
      calmodulin is detected in the low-salt extract. These results suggest that
      calmodulin is the sole Ca2(+)-sensitive factor in the low-salt extract. The main
      target of calmodulin in the erythroid membrane cytoskeleton was further examined.
      Under native conditions, calmodulin forms a stable and equivalent complex with
      protein 4.1 as determined by calmodulin affinity chromatography, cross-linking
      experiments, and fluorescence binding assays with an apparent Kd of 5.5 x 10(-7)
      M irrespective of the free Ca2+ concentration. Domain mapping with chymotryptic
      digestion reveals that the calmodulin-binding site resides within the N-terminal
      30-kDa fragment of protein 4.1. In contrast, the interaction of calmodulin with
      spectrin is unexpectedly weak (Kd = 1.2 x 10(-4) M). Given the content of
      calmodulin in erythrocytes (2-5 microM), these results imply that the major
      target for calmodulin in the erythroid membrane cytoskeleton is protein 4.1. Low-
      and high-shear viscometry and binding assays reveal that an equivalent complex of
      calmodulin with protein 4.1 regulates the spectrin/actin interaction in a Ca2(+)
      dependent manner. At a low Ca2+ concentration, protein 4.1 potentiates the actin
      cross-linking and the actin binding activities of spectrin. At a high Ca2+
      concentration, the protein 4.1-potentiated actin cross-linking activity but not
      the actin binding activity of spectrin is suppressed by Ca2+/calmodulin. The
      Ca2(+)-dependent regulation of the spectrin/protein 4.1/calmodulin/actin
      interaction is discussed.

PMID- 1985940
TI  - Adipsin gene expression in 3T3-F442A adipocytes is posttranscriptionally down
      regulated by retinoic acid.
AB  - Retinoic acid (RA) has been shown to inhibit the differentiation of 3T3
      adipogenic cell lines. In this report, the steady-state levels of several adipose
      specific mRNAs were studied in mature adipocytes treated with RA. Northern blot
      analysis showed that, following a 24-h exposure of 3T3-F442A adipocytic cultures
      to RA (10 microM), there was a 4-5-fold decrease of adipsin mRNA level. In
      contrast, actin, adipocyte P2, lipoprotein lipase, and glycerophosphate
      dehydrogenase mRNA levels were unchanged during the same interval. The rate of
      adipsin and actin gene transcription, assessed by nuclear run-on assays, remained
      unchanged in adipocytes exposed to RA. The half-life (t1/2) of adipsin mRNA,
      determined by pulse-chase with [3H] uridine, was greatly shortened in RA-treated
      adipocytes (t1/2 approximately 7.3 h) as compared with untreated cells (t1/2
      approximately 37.6 h). Conversely, actin mRNA stability was not altered by the
      drug. These results suggest that RA can specifically down-regulate adipsin
      expression in adipocytes at a posttranscriptional level without inducing the
      reversal of adipocyte differentiation.

PMID- 1985941
TI  - The interfacial conformation and transbilayer movement of diacylglycerols in
      phospholipid bilayers.
AB  - The interaction of diacylglycerols, primarily 1,2-dilauroyl-sn-glycerol (1,2
      DLG), with egg phosphatidylcholine (PC) bilayers was studied by NMR spectroscopy
      and other physical techniques. In the low proportions used (less than or equal to
      20 mol % with respect to total lipid), 1,2-DLG formed bilayers with PC with no
      hexagonal phase separation, as assessed by light, polarizing and electron
      microscopy, and 31P and 13C NMR spectroscopy. The 13C-carbonyl chemical shift of
      90% [13C]carbonyl 1,2-DLG was monitored in small unilamellar vesicles as a
      function of relative DLG content (1.5-20%) and temperature (10-55 degrees C). The
      chemically inequivalent sn-1 and sn-2 carbonyls gave a single, narrow resonance
      in vesicles, in contrast to neat 1,2-DLG and 1,2-DLG in organic solvents, whose
      spectra showed two well-separated carbonyl resonances. The chemical shift of 1,2
      DLG in PC shows that the carbonyl groups are proximal to the aqueous interface,
      necessitating orientation of the DLG molecule along the normal to the bilayer.
      Both carbonyl groups are H-bonded to H2O, but the secondary ester (sn-2) carbonyl
      is relatively more hydrated than the primary ester (sn-1) carbonyl. The 13C
      carbonyl chemical shift data further suggest that the interfacial conformation
      resembles that of crystalline and liquid crystalline lamellar 1,2-dilauroyl-sn
      glycero-3-phosphatidylethanolamine and certain PCs, in which the glycerol
      backbone is perpendicular to the bilayer plane. This conformation is different
      from that of crystalline 1,2-dilauroyl-sn-glycerol, in which the glycerol
      backbone is parallel to the bilayer plane. Between 1.5 and 8% DLG in vesicles,
      the chemical shift of the 1,2-DLG carbonyl at a given temperature was constant.
      However, above 8% DLG the chemical shift at each temperature increased with
      increasing DLG concentration, suggesting increased hydration at higher DLG
      content. At low temperatures 13C NMR spectra of vesicles with the highest
      proportions of 1,2-DLG studied (15 and 20%) showed two DLG carbonyl resonances,
      which most likely represent 1,2-DLG on outer and inner leaflets of the vesicle
      bilayer. The two peaks collapsed into a single resonance by 38 degrees C, at
      which temperature the two environments equilibrate with a rate constant of
      approximately 60 s-1 (t1/2 approximately 10 ms). Thus, transbilayer movement of
      DLG is extremely fast compared with phospholipids. In vesicles the 1,3-isomer of
      DLG exhibited a narrow carbonyl peak slightly downfield from that of 1,2-DLG.
      Acyl chain migration from 1,2-DLG to 1,3-DLG was monitored directly in the
      vesicle by time-dependent NMR measurements.

PMID- 1985942
TI  - Association between proteoglycans and matrix vesicles in the extracellular matrix
      of growth plate cartilage.
AB  - Matrix vesicles (MV) are microstructures localized to the extracellular matrix of
      developing hard tissues that induce mineral formation. MV proteins are not well
      characterized, and little is known of how they interact with the surrounding
      matrix. However, recent electron microscopic studies indicate that MV interact
      with matrix proteins in growth plate cartilage. In the studies now reported,
      procedures developed for dissecting various components from isolated MV led to
      the discovery that two major vesicle proteins (38 and 46 kDa) are readily
      released from MV by low ionic strength solutions. These low ionic strength
      soluble proteins (LISSP) were shown to be major fragments of the link protein
      (LP) and hyaluronic acid-binding region (HABR) of matrix proteoglycans: they
      react immunologically with highly specific monoclonal antibodies to LP and HABR,
      and the NH2-terminal sequence of the 38-kDa LISSP is essentially identical to
      residues 40-78 of chicken cartilage LP and that the 46-kDa LISSP represents HABR.
      Release of both LISSP is enhanced by hyaluronidase treatment, indicating
      anchorage by a hyaluronate-mediated mechanism. Both LP and HABR are firmly
      attached to MV in either isotonic or hypertonic solutions. In contrast, our other
      studies show that dissociation of type II collagen from MV occurs only with
      hypertonic salts which do not release the LISSP. Thus, strong interactions occur
      under physiological conditions between MV and both the proteoglycans and
      collagens, but these take place by different mechanisms.

PMID- 1985943
TI  - An alternatively spliced miniexon alters the subcellular fate of the human
      asialoglycoprotein receptor H2 subunit. Endoplasmic reticulum retention and
      degradation or cell surface expression.
AB  - Two types of cDNAs encoding the H2 subunit of the human asialoglycoprotein
      receptor had been cloned, differing only by the presence (H2a) or absence (H2b)
      of a segment of 15 base pairs (bp), encoding five amino acids (Glu-Gly-His-Arg
      Gly) immediately carboxylterminal (exoplasmic) to the single membrane-spanning
      segment. We have cloned and sequenced this region of the H2 gene and showed that
      the two H2 forms are alternatively spliced variants differing in the presence of
      a 15-bp miniexon. Both H2 messenger RNAs were found in HepG2 cells, H2b
      accounting for about 92% of the H2 mRNAs. When expressed in NIH 3T3 cells without
      the H1 receptor subunit, the two-variant polypeptides exhibit different
      subcellular fates. H2a is completely retained in and degraded in the endoplasmic
      reticulum or a related pre-Golgi compartment. In contrast a substantial amount of
      H2b is processed by Golgi enzymes and reaches the cell surface. Thus, the sole
      difference determining the subcellular localization of the two forms if the five
      amino acid insert in H2a. When a virion-packaged retroviral vector containing H2a
      cDNA infected 3T3 cells, 70% of the resulting clones expressed H2b and 30% H2a.
      Thus the 15-bp H2a miniexon can be spliced out, at least during the retrovirus
      life cycle.

PMID- 1985944
TI  - Effect of phorbol esters on cytosolic protein kinase C content and activity in
      the human monoblastoid U937 cell.
AB  - 12-O-Tetradecanoylphorbol-13-acetate (TPA) stimulates the human monoblastoid U937
      cell to differentiate into a mature monocyte/macrophage-like cell. Since TPA may
      produce cellular responses by activating protein kinase C, the effects of TPA on
      kinase activity in the U937 cell were investigated. Brief exposures (less than or
      equal to 60 min) to TPA dramatically diminished protein kinase C-dependent
      phosphorylation of histone and endogenous substrates. However, using a peptide
      substrate corresponding to residues 720-737 of protein kinase C-epsilon, Ca2(+)-,
      phospholipid-, and diacylglycerol-dependent kinase activity was reduced only
      modestly after exposure to TPA. This phospholipid-dependent kinase activity
      coeluted on DEAE chromatography with protein kinase C. Examination of cytosolic
      protein kinase C content by Western blot analysis demonstrated a moderate decline
      in kinase content after TPA treatment. The decline was due primarily to loss of
      an 80-kDa species with preservation of a 76-kDa protein. The immunoreactive 76
      kDa protein observed after TPA treatment comigrated on DEAE chromatography with
      the kinase activity phosphorylating the protein kinase C-epsilon peptide and had
      an elution profile similar to protein kinase C derived from untreated cells.
      Using antisera recognizing the catalytic and regulatory domains of the kinase, no
      evidence for proteolytic degradation of protein kinase C was observed. Although
      incubation of extracts from vehicle and TPA-treated cells inhibited the activity
      of partially purified protein kinase C, the degree of inhibition was similar in
      the two extracts. These findings suggest that TPA markedly diminishes protein
      kinase C-dependent phosphorylation of histone and endogenous substrates in part
      by altering kinase substrate specificity. These observations provide evidence for
      a novel post-translational process that can modulate protein kinase C-dependent
      phosphorylation.

PMID- 1985945
TI  - The role of N3-ethyldeoxythymidine in mutagenesis and cytotoxicity by ethylating
      agents.
AB  - The significance of DNA ethylation at the central hydrogen-bonding site (N3) of
      thymine was investigated using an in vitro DNA replication system. The system
      utilized a primed template in which the 3'-end of the primer is eight nucleotides
      away from N3-ethyldeoxythymidine (N3-Et-dT), present at template position 26 from
      the 3'-end. The 34-nucleotide template corresponds to a specific DNA sequence at
      gene G of bacteriophage phi X174. DNA synthesis products were quantitated by
      electrophoretic separation and autoradiography. At 10 microM dNTP and 0.5 mM
      Mn2+, N3-Et-dT blocked DNA synthesis by Escherichia coli polymerase I (Klenow
      fragment): 60% after incorporating a nucleotide opposite N3-Et-dT (incorporation
      dependent blocked product) and 39% 3' to N3-Et-dT. DNA replication past the
      lesion (post-lesion synthesis) was negligible. Post-lesion synthesis increased
      using higher concentrations of dNTP, reaching 68% at 200 microM dNTP. DNA
      sequencing revealed that dA was incorporated opposite N3-Et-dT in the
      incorporation-dependent blocked product. In the post-lesion synthesis product, dT
      was exclusively incorporated opposite N3-Et-dT. Formation of the N3-Et-dT.dA base
      pair at the replication fork terminated DNA synthesis, while the N3-Et-dT.dT base
      pair formed at the 3'-end of the growing chain was extended, leading to an A.T---
      T.A transversion mutation. The results suggest a dual role for the N3-Et-dT
      lesion, contributing in part to the cytotoxicity and mutagenicity of ethylating
      agents. These studies provide a basis for understanding the activation of
      oncogene neu by A.T----T.A transversion mutation in rat neuroblastomas induced by
      N-ethyl-N-nitrosourea.

PMID- 1985946
TI  - Mitochondrial phosphate transport. Import of the H+/Pi symporter and role of the
      presequence.
AB  - The rat liver mitochondrial phosphate transporter contains a 44-amino acid
      presequence. The role of this presequence is not clear since the ADP/ATP carrier
      and the brown fat uncoupling protein, related members of a family of inner
      membrane anion transporters, lack a presequence and contain targeting information
      within the mature protein. Here, we present evidence that the rat liver
      mitochondrial phosphate transporter can be synthesized in vitro, imported into
      mitochondria, and processed to a protein of Mr 33,000. Import requires the
      membrane potential and external nucleotide triphosphate. The presequence inserts
      into the outer mitochondrial membrane, and import proceeds via a process similar
      to other proteins destined for the inner membrane or matrix. A mutant phosphate
      transporter lacking 35 amino acids at the NH2 terminus of the presequence has
      little capacity for mitochondrial import. The rat liver phosphate transporter is
      also imported and processed by rat kidney mitochondria and by mitochondria from
      the yeast Saccharomyces cerevisiae. A site-directed mutation of the N-ethyl
      maleimide reactive cysteine 41 does not affect import or processing. The results
      presented show that optimal import of the mitochondrial phosphate transporter,
      unlike the ADP/ATP carrier and the brown fat uncoupling protein, is dependent on
      a presequence. As these carriers are believed to have evolved from a single gene,
      it seems likely that the H+/Pi carrier, known to be present in prokaryotes,
      appeared first and that subsequent evolutionary events leading to the other anion
      carriers eliminated the presequence.

PMID- 1985947
TI  - DNA-binding properties of a lac repressor mutant incapable of forming tetramers.
AB  - The interaction of proteins bound to sites widely separated on the genome is a
      recurrent motif in both prokaryotic and eukaryotic regulatory systems. Lac
      repressor mediates the formation of "DNA loops" by the simultaneous interaction
      of a single protein tetramer with two DNA-binding sites. The DNA-binding
      properties of a Lac repressor mutant (LacIadi) deficient in the association of
      protein dimers to tetramers was investigated. The results of quantitative
      footprint and gel mobility-shift titrations suggest that the wild-type Lac
      repressor (LacI+) binds cooperatively to two operator sites separated by 11
      helical turns on a linear DNA restriction fragment by the formation of a "looped
      complex." LacIadi binds to this two-site operator non-cooperatively and without
      formation of a looped complex. These results demonstrate that the dimer-tetramer
      association of LacI+ is directly responsible for its cooperative binding and its
      ability to mediate formation of a looped complex. The Iadi mutation disrupts the
      monomer-dimer as well as eliminating the dimer-tetramer association equilibria
      while the DNA binding affinity of LacIadi to a single site is unchanged relative
      to the wild-type protein. These results suggest that DNA binding and dimer
      tetramer association are functionally unlinked. The similarity of the DNA-binding
      properties of LacIadi and Gal repressor, a protein believed to function by
      mediating the formation of a looped complex, are discussed.

PMID- 1985948
TI  - Cyclosporin A slows collagen triple-helix formation in vivo: indirect evidence
      for a physiologic role of peptidyl-prolyl cis-trans-isomerase.
AB  - Peptidyl-prolyl cis-trans-isomerase accelerates otherwise slow, rate-limiting
      isomerization steps during folding of proteins in vitro, but is not yet securely
      identified with any specific physiologic role. Peptidyl-prolyl cis-trans
      isomerase and the cyclosporin A (CsA)-binding protein cyclophilin are identical,
      and peptidyl-prolyl cis-trans-isomerase activity is inhibited by the
      immunosuppressive drug CsA in vitro. To establish a possible physiologic role of
      peptidyl-prolyl cis-trans-isomerase, we have studied the folding of procollagen I
      in suspended chick embryo tendon fibroblasts. Folding of procollagen I is slowed
      by CsA: the time needed for 50% of the molecules to reach a completely helical
      confirmation is 8.5 min in the absence and 13.5 min in the presence of 5 microM
      CsA; and the calculated products, k x K, of the rate constant (k) and the
      equilibrium constant (K) of peptidyl-prolyl cis-trans isomerization are 2.10 and
      1.30 s-1, respectively. In contrast, folding of purified collagen III in vitro is
      unaffected by CsA. In cultured human fibroblasts, CsA caused posttranslational
      overmodification (hydroxylation of lysine 32.1 versus 22.1%) and increased
      intracellular degradation (18.7 versus 12.5%), and hence decreased production
      (10.2 versus 13.2% of total protein synthesis) of collagens I and III, indicating
      that procollagen folding is slowed by CsA also in human fibroblasts. We conclude
      that peptidyl-prolyl cis-transisomerase (and hence cyclophilin) accelerates
      protein folding in living cells. Furthermore, the CsA-induced changes in collagen
      metabolism are reminiscent of those observed in several variants of osteogenesis
      imperfecta caused by structural abnormalities in the pro-collagen chains which
      impair helix formation.

PMID- 1985949
TI  - RNA polymerase activity may regulate transcription initiation and attenuation in
      the rplKAJLrpoBC operon in Escherichia coli.
AB  - The relationship between global RNA transcription capacity and transcript
      initiation, attenuation, and stability in the rplKAJLrpoBC operon of Escherichia
      coli has been examined. The rplKAJLrpoBC operon encodes in order the four large
      ribosome subunit proteins, L11, L1, L10, and L12, and the two large beta and
      beta' subunits of RNA polymerase. Operon transcripts are initiated at two
      promoters, PL11 and PL10. The L12-beta intergenic space contains a transcription
      attenuator which, during balanced growth, terminates about 80% of the transcripts
      exiting the L12 gene; the remaining transcripts read through into the beta and
      beta' encoding genes. The capacity for global transcription initiation was
      modulated using a strain carrying a temperature-sensitive, initiation-defective
      mutation in rpoC. Following a shift to 39 degrees C, the global transcription
      initiation capacity was reduced to about one-half the level at 30 degrees C. This
      partial restriction resulted in a decrease in the stability of distal beta mRNA,
      whereas the stability of proximal L11-L1 and L10-L12 mRNA was not changed.
      Measurements of the synthesis rates of L11-L1, L10-L12, and beta mRNAs relative
      to total RNA synthesis indicated that this operon was selectively transcribed
      when the initiation capacity of RNA polymerase was limited. The synthesis rates
      of L11-L1 and L10-L12 mRNA increased about 2-fold, whereas the synthesis rate of
      beta mRNA increased nearly 5-fold. The relative transcription of other ribosome
      component genes and the alpha subunit gene exhibited only a modest increase
      during the partial restriction. Protection from S1 nuclease was used to
      demonstrate that the preferential transcription within the operon of beta mRNA
      was the consequence of active regulation of termination-antitermination at the
      attenuator structure in the L12-beta intergenic space. These results demonstrate
      that global transcription capacity may be an important parameter in determining
      both initiation and attenuation of transcription of the rplKAJLrpoBC ribosomal
      protein-RNA polymerase operon.

PMID- 1985950
TI  - Cell-free synthesis of rat glucocorticoid receptor in rabbit reticulocyte lysate.
      In vitro synthesis of receptor in Mr 90,000 heat shock protein-depleted lysate.
AB  - The glucocorticoid receptor is present in the cytosol of cell extracts as a large
      nonactivated (i.e. non-DNA-binding) approximately 9 S (Mr 300,000) complex.
      Experimental evidence indicates that the purified nonactivated glucocorticoid
      receptor contains a single steroid-binding protein and two approximately 90-kDa
      nonsteroid-binding subunits identified as heat shock protein (hsp) 90.
      Translation of the glucocorticoid receptor mRNA in vitro in reticulocyte lysates
      produces a large nonactivated glucocorticoid receptor complex similar to that
      found in cytosols. The cell-free synthesized glucocorticoid receptor is able to
      bind steroid and can be activated further to the DNA-binding form. To test the
      hypothesis of an active role played by hsp90 in the stabilization of a competent
      steroid-binding conformation of the glucocorticoid receptor, we have synthesized
      the receptor in a reticulocyte lysate that has been depleted of hsp90 by
      immunoadsorption with AC88 anti-hsp90. Although the translation capacity of the
      reticulocyte system was reduced considerably upon hsp90 removal, the
      glucocorticoid receptor was synthesized, and a significant number of molecules
      were found to bind [3H]triamcinolone acetonide. Chromatography on DEAE-cellulose
      showed that most of the receptor molecules synthesized in hsp90-depleted lysate
      had lost the capacity to form an oligomeric receptor complex. Addition of
      purified rat liver hsp90 to the hsp90-depleted lysate before translation did not
      increase steroid binding nor did it restore formation of the heteromeric receptor
      complex. Analysis of [35S] methionine-labeled glucocorticoid receptor molecules
      synthesized in the hsp90-depleted lysate showed the production of polypeptides
      differing from the expected chromatographic pattern on DEAE-cellulose. Upon
      addition of purified hsp90 to the hsp90-depleted lysate, before translation, the
      35S-labeled synthesized receptor fractionated on DEAE-cellulose as an
      intermediate peak between activated and nonactivated receptor forms. The data
      suggest that hsp90 alone may not be sufficient for the formation of the
      nonactivated steroid receptor complex.

PMID- 1985951
TI  - Glucose regulates leucine-induced insulin release and the expression of the
      branched chain ketoacid dehydrogenase E1 alpha subunit gene in pancreatic islets.
AB  - Much evidence has accumulated to support the idea that leucine can stimulate
      insulin release by allosterically activating glutamate dehydrogenase thus
      enhancing glutamate metabolism. It is less clear how the metabolism of leucine
      itself contributes to the signal for insulin release. We recently found that
      culturing pancreatic islets for 1 day at low glucose (1 mM) suppressed glucose
      induced insulin release, but preserved leucine-induced insulin release. When
      islets were cultured at high glucose (20 mM), glucose-induced insulin release was
      preserved, but leucine-induced insulin release was suppressed (MacDonald, M. J.,
      Fahien, L. A., McKenzie, D. I., and Moran, S. M. (1990) Am. J. Physiol., 259,
      E548-E554). The suppression of leucine-induced insulin release can be explained
      by glucose's suppression of the synthesis of the enzyme that catalyzes the first
      committed step of leucine metabolism, branched chain ketoacid dehydrogenase
      complex (BCKDH). High glucose suppressed the enzyme activity of the E1 component
      of the BCKDH complex, as well as the total activity of the BCKDH complex, to
      usually negligible levels in islets and decreased by an average of 90% the mRNA
      which encodes E1 alpha, the catalytic subunit of the E1 component of BCKDH, in
      islets and rat insulinoma cells. Time course studies showed that about 24 h in
      culture was required to maximally induce or suppress the expression of BCKDH E1
      alpha. Culture at high glutamine with or without leucine mimicked to a lesser and
      more variable degree the effects of high glucose on leucine-induced insulin
      release and BCKDH E1 alpha mRNA. Leucine-plus-glutamine-induced insulin release
      was present after culture of islets with glucose and with or without any other
      secretagogue. Also, glutamate dehydrogenase transcripts and enzyme activity were
      not significantly altered by varying the concentration of glucose in the culture
      medium. Thus, leucine's insulinotropism via activation of glutamate dehydrogenase
      is constitutive. Preproinsulin mRNA levels were markedly increased at high
      glucose and glyceraldehyde phosphate dehydrogenase transcripts were either
      unaffected or slightly increased by glucose. Glutamine did not significantly
      effect the expression of genes other than BCKDH E1 alpha, and leucine had little
      or no effect on the expression of any of the four genes.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 1985952
TI  - Glycocalyx of bodies versus tails of Schistosoma mansoni cercariae. Lectin
      binding, size, charge, and electron microscopic characterization.
AB  - Infection with Schistosoma mansoni is initiated by penetration of the intact skin
      of the mammalian host with the head but not the tail of the parasite cercariae.
      The surface of cercariae is covered by a 1-2-micron thick carbohydrate-rich
      glycocalyx (gx). Furthermore, the transformation of cercariae to schistosomula
      (the next parasitic stage in the mammalian host) is associated with loss of gx
      from the bodies. To understand the role of gx in the host-parasite relationship,
      we have characterized the gx of both bodies and tails of S. mansoni cercariae. A
      fluorescent fucose-specific lectin-stained bodies and not tails of the organism.
      Moreover, when an enriched preparation of gx obtained by extraction with 40%
      aqueous phenol and exclusion from Sepharose CL-6B was subjected to affinity
      chromatography on insolubilized Lotus lectin, which binds fucose-containing
      glycans, only body gx was retained. Body gx is smaller and less negatively
      charged than tail gx. Electron microscopy showed that gx from bodies and tails is
      composed of 25-40-nm particles and fibrillar material. Carbohydrate composition
      of gx of bodies and tails indicate that fucose and glucose are major components,
      respectively. beta-Elimination experiments indicate that the linkage sugar is N
      acetylgalactosamine in both cases. Upon treatment with alkaline borohydride,
      nearly 90% of gx of both bodies and tails was recovered as two glycan chains: I
      and II (Mr approximately 10,500 and 5,600, respectively). Glycan I was in both
      cases more negatively charged than glycan II. Fucose is the predominant sugar in
      glycan I of the bodies while glycan I of tails is mainly composed of glucose. The
      gx was resistant to several proteases. This resistance and the abundance of
      carbohydrate in gx may be of biological importance for survival of cercariae. The
      substantial differences observed between the gx of bodies and tails may provide
      the basis for understanding the mechanism of selective release of body gx during
      transformation.

PMID- 1985953
TI  - Linker mutagenesis of a bacterial fatty acid transport protein. Identification of
      domains with functional importance.
AB  - The product of the fadL gene (FadL) of Escherichia coli is a multifunctional
      integral outer-membrane protein required for the specific binding and transport
      of exogenous long-chain fatty acids [C12-C18]. FadL also serves as a receptor for
      the bacteriophage T2. In order to define regions of functional importance within
      FadL, the fadL gene has been mutagenized by the insertion of single-stranded
      hexameric linkers into the unique SalI restriction site that lies towards the 3'
      end of the gene and into four HpaII restriction sites distributed throughout the
      coding region. The five insertion mutants were classified into three groups based
      on their specific growth rates (alpha) in minimal media containing the long-chain
      fatty acid oleate (C18:1) as a sole carbon and energy source: Oleslow, alpha =
      0.035-0.045; Ole +/-, alpha = 0.020-0.035; and Ole-, alpha less than or equal to
      0.005 (wild-type, alpha = 0.07-0.10). The hexameric insertion at the SalI site
      (fadL allele termed S1; insertion after amino acid 410) conferred an Oleslow
      phenotype and resulted in a reduction of long-chain fatty acid transport (36% the
      wild-type level). This insertion mutant, however, bound oleic acid at wild-type
      levels and was fully functional as a receptor for the bacteriophage T2. The
      modified FadL-S1 protein did not have the heat-modifiable property characteristic
      of wild-type FadL. Insertions in the four HpaII sites (fadL alleles termed H1,
      H2, H3, and H5; after amino acids 41, 81, 238, and 389, respectively) resulted in
      all three classes of mutants. The fadL insertion mutant H5 was defective for long
      chain fatty acid transport but bound oleic acid at significant levels. Together
      with the S1 allele, these data suggest that the carboxyl terminus of FadL is
      crucial for long-chain fatty acid transport. The insertion mutants H1 and H2 were
      defective for both oleic acid binding and transport suggesting that the amino
      terminus of FadL is important for long-chain fatty acid binding and transport.
      The fadL linker mutant H3 was defective in oleic acid binding yet had significant
      levels of oleic acid transport. These studies delineated for the first time
      different regions of the fadL gene that encode domains of FadL implicated in the
      binding and transport of long-chain fatty acids.

PMID- 1985954
TI  - HNF-1, a member of a novel class of dimerizing homeodomain proteins.

PMID- 1985955
TI  - Erythropoietin increases c-myc mRNA by a protein kinase C-dependent pathway.
AB  - The peptide hormone erythropoietin is a major regulator of red blood cell
      production. While red blood cell development has been studied intensively, little
      is known about the intracellular signaling events that follow the binding of
      erythropoietin to its receptor on the target cell. We report here that
      erythropoietin-induced activation of the immediate early gene c-myc requires
      protein kinase C and that the binding of erythropoietin causes rapid
      phosphorylation of the major protein kinase C substrate, p80. Our results also
      argue for modulation of activity of a second signal transduction element in
      addition to protein kinase C.

PMID- 1985956
TI  - Hirudin: amino-terminal residues play a major role in the interaction with
      thrombin.
AB  - Amino acid substitutions within the amino-terminal 5 residues of the thrombin
      specific inhibitor hirudin dramatically alter its ability to inhibit the thrombin
      catalyzed hydrolysis of both a chromogenic substrate and fibrinogen. Replacing
      the highly conserved Tyr-3 residue with Trp or Phe increases hirudin's affinity
      for thrombin 3-6-fold (decreases the inhibition constant, Ki) whereas Thr results
      in a 450-fold increase in Ki. A more extensive modification involving deletion of
      the amino-terminal Val, and Tyr-3----Val, Thr-4----Gln, and Asp-5----Ile
      replacement, results in a large reduction in thrombin inhibitory activity
      corresponding to greater than a 10(7)-fold increase in Ki and a 10(3)-fold
      increase in IC50, using D-Phe-L-pipecolyl-Arg-p-nitroanilide (S-2238) and
      fibrinogen, respectively, as substrates. Kinetic analysis of these mutant
      proteins and synthetic peptide fragments and available structural information on
      thrombin and hirudin derived from protein crystallography and two-dimensional NMR
      studies indicate that the amino-terminal region of hirudin binds at the apolar
      binding/active site region of thrombin, with Tyr-3 occupying the S3 specificity
      site. The large effect of these modifications on hirudin activity suggests that
      alteration of the amino-terminal segment can destabilize the interaction of other
      regions of hirudin with thrombin.

PMID- 1985957
TI  - Purification and characterization of the yeast negative regulatory protein GAL80.
AB  - Transcription of the GAL genes encoding the enzymes responsible for galactose
      metabolism in the yeast Saccharomyces cerevisiae is regulated through an
      interplay of two regulatory proteins, GAL4 and GAL80. GAL4 binds to upstream
      activating sequences of GAL (UASG) and activates their transcription in yeast
      growing in the presence of galactose. GAL80 binds to GAL4 and inhibits the
      activation function of GAL4 in yeast growing without galactose. We have purified
      GAL80 in its native form as a protein that reacts with an antiserum raised
      against a synthetic peptide of 18 amino acid residues in the GAL80 sequence.
      Purification was performed through ammonium sulfate precipitation, streptomycin
      precipitation, DEAE-cellulose column chromatography, and gel filtration. From 50
      g of wet cells, a final sample of 2.3 mg with a purity of more than 80% was
      obtained. The molecular size of the purified protein in both the native and
      denatured states was estimated to be approximately 50 kDa, indicating that GAL80
      exists as a monomer in yeast cells. The amino-terminal residue of GAL80 was found
      to be acetylmethionine. The purified protein was shown to bind GAL4. We have also
      purified mutant GAL80 proteins encoded by two different alleles of gal80 known to
      be incapable of inhibiting the function of GAL4. These proteins were, in fact,
      unable to bind GAL4.

PMID- 1985958
TI  - Leukocyte chemoattractant peptides from the serpin heparin cofactor II.
AB  - Heparin cofactor II (HC) is a plasma serine proteinase inhibitor (serpin) that
      inhibits the coagulant proteinase alpha-thrombin. We have recently demonstrated
      that proteolysis of HC by catalytic amounts of polymorphonuclear leukocyte
      proteinases (elastase or cathepsin G) generates leukocyte chemotaxins (Hoffman,
      M., Pratt, C. W., Brown, R. L., and Church, F. C. (1989) Blood 73, 1682-1685).
      One of four peptides produced when HC is degraded by neutrophil elastase has
      chemotactic activity for both monocytes and neutrophils with maximal migration
      comparable to formyl-Met-Leu-Phe, the "gold standard" bacterially derived
      chemotaxin. The amino-terminal sequence of this HC peptide is Asp-Phe-His-Lys-Glu
      Asn-Thr-Val-... and the peptide corresponds to Asp-39 to Ile-66 of HC. A variety
      of synthetic peptides derived from this sequence were evaluated for leukocyte
      migration activity, and a dodecapeptide from Asp-49 to Tyr-60 (Asp-Trp-Ile-Pro
      Glu-Gly-Glu-Glu-Asp-Asp-Asp-Tyr) was identified as the active site for leukocyte
      chemotactic action. The 12-mer synthetic peptide possesses significant neutrophil
      chemotactic action at 1 nM (60% of the maximal activity of formyl-Met-Leu-Phe),
      while a peptide with the reverse sequence has essentially no chemotactic
      activity. Cross-desensitization experiments also show that pretreatment of
      neutrophils with a 19-mer peptide (Asn-48 to Ile-66) greatly reduces subsequent
      chemotaxis to HC-neutrophil elastase proteolysis reaction products. When injected
      intraperitoneally in mice, the HC-neutrophil elastase digest elicits neutrophil
      migration. Our results demonstrate that not only does HC function as a thrombin
      inhibitor, but that limited proteolysis of HC near the amino terminus yields
      biologically active peptide(s) which might participate in inflammation and in
      wound healing and tissue repair processes.

PMID- 1985959
TI  - Increases in cytosolic calcium ion concentration can be dissociated from the
      killing of cultured hepatocytes by tert-butyl hydroperoxide.
AB  - Digital imaging fluorescence microscopy was used to study the effect of tert
      butyl hydroperoxide (TBHP) on the cytosolic free calcium concentration ([Ca2+]i)
      of single rat hepatocytes in primary culture. Within minutes of the addition of
      TBHP, individual hepatocytes displayed one or more peaks of increased [Ca2+]i
      that promptly returned to the prestimulation level. This was followed by a slower
      increase of [Ca2+]i that reached a plateau of 696 +/- 260 nM (basal 194 +/- nM)
      after 20 min. Another rise in [Ca2+]i, abrupt and much larger, preceded the death
      of the cells after about 45 min. Pretreatment of the hepatocytes with
      deferoxamine, a ferric iron chelator, or the addition of the antioxidants N,N'
      diphenyl-p-phenylenediamine or catechol prevented the loss of viability. Neither
      the number of hepatocytes displaying the initial [Ca2+]i transients nor the
      magnitude of these oscillations was affected by deferoxamine, N,N'-diphenyl-p
      phenyl-enediamine, or catechol. However, both the plateau phase and the abrupt
      rise in [Ca2+]i were prevented. Treatment of the hepatocytes with TBHP in a low
      calcium buffer (less than 2 microM Ca2+) reduced or abolished the initial [Ca2+]i
      transients and eliminated both the plateau phase and abrupt rise in [Ca2+]i. The
      onset of cell death was delayed by 10 min in the low calcium medium. Addition of
      3.5 mM EGTA to the cultures lowered the basal calcium concentration, prevented
      both the initial [Ca2+]i spikes and the delayed changes, and further prolonged
      the onset of cell death. These data indicate that the killing of the cultured
      hepatocytes by TBHP can be dissociated from changes in intracellular calcium
      homeostasis. An influx of extracellular Ca2+ ions may aggravate somewhat the
      mechanisms of cell injury by an oxidative stress and accelerate the time of onset
      of cell death.

PMID- 1985960
TI  - Isolation and complete amino acid sequence of the mitochondrial ATP synthase
      epsilon-subunit of the yeast Saccharomyces cerevisiae.
AB  - All five subunits of yeast mitochondrial F1-ATPase have been isolated by reverse
      phase high performance liquid chromatography. This procedure allows micro
      preparative purification of all the subunits with 60% recoveries. The complete
      amino acid sequence of the epsilon-subunit has been established. This has been
      achieved by the sequence analysis of subnanomole amounts of the intact molecule
      and that of peptides derived by enzymatic digestion with endoproteinase Arg-C and
      by chemical cleavage with hydroxylamine. Yeast ATP synthase epsilon-subunit is
      composed of 61 residues with a calculated molecular mass of 6612 Da. This
      polypeptide is rather basic since it contains 7 basic residues and 3 acidic
      residues. This study shows a slight similarity with the bovine epsilon-subunit
      ATP synthase since there are 16 identical residues.

PMID- 1985961
TI  - Interactions among cytochromes P-450 in the endoplasmic reticulum. Detection of
      chemically cross-linked complexes with monoclonal antibodies.
AB  - The quaternary structure of rat liver cytochrome P-450 within microsomal
      membranes from 3-methyl-cholanthrene-treated rats was examined by a novel
      chemical cross-linking-monoclonal antibody approach. Complex formation among the
      different forms of P-450 was probed by cross-linking of membrane proteins
      followed by immunopurification with a monoclonal antibody (mAb) to P-450c, the
      major 3-methylcholanthrene-inducible form. Subsequent immunoblot analysis of the
      immunopurified proteins with this mAb indicated that P-450c formed complexes with
      other microsomal proteins. Immunoblots with mAbs to different P-450s were carried
      out to identify the P-450s that were cross-linked to P-450c. This approach
      detected specific cross-linking of P-450c to P-450 2a. Immunoinhibition
      experiments suggest that P-450 2a further metabolizes the primary phenols
      produced by P-450c-catalyzed hydroxylation of benzo[a]pyrene. Complex formation
      among membrane-bound enzymes has implications for their catalytic efficiency and
      an approach combining cross-linking and monoclonal antibody-based
      characterization of cross-linked proteins will be useful for elucidating such
      membrane protein macrostructures.

PMID- 1985962
TI  - The origin of reaction specificity in serine hydroxymethyltransferase.
AB  - Cytosolic serine hydroxymethyltransferase has been shown previously to exhibit
      both broad substrate and reaction specificity. In addition to cleaving many
      different 3-hydroxyamino acids to glycine and an aldehyde, the enzyme also
      catalyzes with several amino acid substrate analogs decarboxylation,
      transamination, and racemization reactions. To elucidate the relationship of the
      structure of the substrate to reaction specificity, the interaction of both amino
      acid and folate substrates and substrate analogs with the enzyme has been studied
      by three different methods. These methods include investigating the effects of
      substrates and substrate analogs on the thermal denaturation properties of the
      enzyme by differential scanning calorimetry, determining the rate of peptide
      hydrogen exchange with solvent protons, and measuring the optical activity of the
      active site pyridoxal phosphate. All three methods suggest that the enzyme exists
      as an equilibrium between "open" and "closed" forms. Amino acid substrates enter
      and leave the active site in the open form, but catalysis occurs in the closed
      form. The data suggest that the amino acid analogs that undergo alternate
      reactions, such as racemization and transamination, bind only to the open form of
      the enzyme and that the alternate reactions occur in the open form. Therefore,
      one role for forming the closed form of the enzyme is to block side reactions and
      confer reaction specificity.

PMID- 1985963
TI  - Cloning and sequencing of cDNA encoding rat GTP cyclohydrolase I. The first
      enzyme of the tetrahydrobiopterin biosynthetic pathway.
AB  - A full-length cDNA clone for GTP cyclohydrolase I, the first enzyme of the
      tetrahydrobiopterin biosynthetic pathway, was isolated and characterized.
      Synthetic oligonucleotides, constructed according to selected amino acid
      sequences of purified GTP cyclohydrolase I, were used to screen a rat liver cDNA
      library. Four clones were isolated, and the length of the longest cDNA insert was
      1024 base pairs. The identity of the cDNA was confirmed by amino acid sequence
      data for eight fragments obtained by lysyl endopeptidase digestion of the
      purified protein. The coding region encoded a protein of 241 amino acid residues,
      but the NH2 terminus of the protein contained 11 additional amino acid residues
      not present in the purified protein. RNA blot analysis showed a single mRNA
      species of 1.2 kilobases in rat liver. A characteristic feature of the deduced
      amino acid sequence of GTP cyclohydrolase I was the presence of sequences similar
      to those proposed for the phosphorylation sites for casein kinase II and growth
      associated histone H1 kinase. Furthermore, significant similarity was found to
      the highly conserved sequences of dihydrofolate reductases, which are known to be
      involved in the binding of the pterin group of dihydrofolate to the reductases.
      This region in GTP cyclohydrolase I may be assigned to the binding site of
      tetrahydrobiopterin, one of the inhibitors of this enzyme.

PMID- 1985964
TI  - Rat pancreatic stone protein messenger RNA. Abundant expression in mature
      exocrine cells, regulation by food content, and sequence identity with the
      endocrine reg transcript.
AB  - We used a cDNA encoding the human pancreatic stone protein (PSP-S), the secretory
      inhibitor of CaCO3 crystal growth, as a probe for cloning rat PSP-S messenger
      RNA. Overlapping clones gave a mRNA sequence of 783 nucleotides encoding a
      preprotein of 165 amino acids including a prepeptide of 21 amino acids. Rat and
      human PSP-S showed 70% identity, and the mature proteins had the same length. PSP
      S mRNA concentration was measured in the pancreas of rats adapted to diets
      containing 15, 25, or 70% protein. Compared with the 15% protein diet,
      concentration increased 3 and 12 times with the diets with 25 and 70% protein,
      respectively, which is 3 times higher than for serine proteases. A complete
      sequence identity was observed between the rat PSP-S transcript and the reg mRNA
      described by Terazono et al. (Terazono, K., Yamamoto, H., Takasawa, S., Shiga,
      K., Yonemura, Y., Tochino, Y., and Okamoto, H. (1988) J. Biol. Chem. 263, 2111
      2114), which is expressed in regenerating pancreatic islets but not in mature
      islets. A specific role of the reg protein in islet regeneration was suggested.
      We found that PSP-S (reg) mRNA concentration was indeed increased in isolated
      regenerating islets. Yet, a transient increase was also observed in exocrine
      tissue during the initial phase of regeneration following pancreatectomy or acute
      pancreatitis, suggesting increased expression during cell dedifferentiation. It
      is concluded that, in mature pancreas, expression of the reg/PSP-S gene occurs
      primarily in acinar cells. The gene product, which encodes a secretory protein
      inhibiting CaCO3 crystal growth in juice, is unlikely to play a specific role in
      islet regeneration.

PMID- 1985965
TI  - Modification of system A amino acid carrier by diethyl pyrocarbonate.
AB  - Sodium-dependent alanine transport in plasma membrane vesicles from rat liver was
      inactivated in a time- and concentration-dependent fashion by prior treatment of
      membranes with the acylating reagent diethyl pyrocarbonate (DEPC). Both
      components of Na+/alanine cotransport (systems A and ASC) were inhibited.
      Exposure of vesicles to p-bromophenacyl bromide and methyl p
      nitrobenzenesulfonate, which share with DEPC reactivity against histidine
      residues, also led to inhibition of alanine transport through systems A and ASC.
      The presence of Na+ (100 mM NaCl) and L-alanine (10 mM) during exposure to
      vesicles to DEPC protected against inactivation of system A (but not system ASC)
      transport activity. This protective effect was specific and required the presence
      of L-alanine since the presence of L-phenylalanine alone (10 mM) or L
      phenylalanine plus Na+ (100 mM NaCl) did not cause any detectable protection.
      This overall pattern of protection is opposite to that previously found against
      specific sulfhydryl reagents (i.e. N-ethylmaleimide), where protection of system
      ASC was nearly maximal. The pH profile for DEPC-dependent inhibition of system A
      transport activity suggests modification of amino acid residue(s) with a pKr of
      approximately 7, most likely histidine(s), in close parallel with the pH
      dependence of system A transport activity. Our results suggest the presence of
      critical histidine residues on the system A carrier that may be responsible for
      the pH dependence of system A transport activity.

PMID- 1985966
TI  - Isolation and characterization of a cDNA clone that codes for human
      spermidine/spermine N1-acetyltransferase.
AB  - Spermidine/spermine N1-acetyltransferase (Spd/Spm acetyltransferase) is the rate
      limiting enzyme in the catabolism of polyamines. This enzyme is highly inducible
      by several stimuli, including the natural polyamines and their structural
      analogues. To investigate the underlying mechanism responsible for the control of
      this enzyme a cDNA which codes for an active human Spd/Spm acetyltransferase has
      been isolated from a random primed cDNA library constructed from mRNA of a
      polyamine analogue treated large cell lung carcinoma line, NCI H157. The 972-base
      pair cDNA was identified using a 32-fold degenerate, 20-base oligomer probe to a
      7-amino acid polypeptide sequence derived from the purified protein. The cDNA has
      a 513-base open reading frame that codes for a protein of 171 amino acids with a
      predicted molecular weight of 20,023. In vitro translation studies demonstrated
      the protein product of this cDNA to be a biologically active enzyme. The cDNA
      recognizes a 1.5-kilobase transcript in human cells which is highly induced in
      the human large cell lung carcinoma NCI H157 line following treatment with the
      polyamine analogue. The unusually high expression of Spd/Spm acetyltransferase
      mRNA by the NCI H157 cells in response to treatment does not appear to be a
      result of an amplification of the Spd/Spm acetyltransferase gene.

PMID- 1985967
TI  - Glucose uptake by Trypanosoma brucei. Rate-limiting steps in glycolysis and
      regulation of the glycolytic flux.
AB  - Glucose uptake and metabolism in the bloodstream form of the glycosome-containing
      protozoan parasite Trypanosoma brucei was measured using 14C-labeled glucose in
      combination with the silicone oil centrifugation technique in short term (5-60 s)
      incubations. Glucose rather than glucose analogues was used to study the
      interrelation between the uptake process and the subsequent metabolic steps.
      Glucose uptake over the plasma membrane occurred by facilitated diffusion, which
      limited the overall glycolytic rate at external glucose concentrations (glcout)
      below 5 mM. At higher glcout another step, either transport over the glycosomal
      membrane or phosphorylation by hexokinase became rate-limiting. Mathematical
      modeling assuming that glucose uptake occurs by facilitated diffusion followed by
      an enzymatic step accurately predicts the experimental data. As predicted by the
      model, the internal concentration of non-metabolized glucose remains low till
      glcout = 5 mM and increases at higher external concentrations. In contrast to
      glucose, glycerol entered the cell by simple diffusion. Externally supplied
      glycerol did not affect glucose metabolism but externally added glucose
      interfered with glycerol metabolism in a way that suggests that the rate-limiting
      step is at the level of glycerol kinase. Our observations suggest that the
      bloodstream form of T. brucei adapts its glucose transport in a way that gives
      maximum yield at minimum expense.

PMID- 1985968
TI  - The OPI1 gene of Saccharomyces cerevisiae, a negative regulator of phospholipid
      biosynthesis, encodes a protein containing polyglutamine tracts and a leucine
      zipper.
AB  - In Saccharomyces cerevisiae, recessive mutations at the OPI1 locus result in
      constitutively derepressed expression of inositol 1-phosphate synthase, the
      product of the INO1 gene. Many of the other enzymes involved in phospholipid
      biosynthesis are also expressed at high derepressed levels in opi1 mutants. Thus,
      the OPI1 gene is believed to encode a negative regulator that is required to
      repress a whole subset of structural genes encoding for phospholipid biosynthetic
      enzymes. In this study, the OPI1 gene was mapped to chromosome VIII and cloned.
      When transformed into an opi1 mutant, the cloned DNA was capable of complementing
      the mutant phenotype and restoring correct regulation to the INO1 structural
      gene. Construction of two opi1 disruption alleles and subsequent genetic analysis
      of strains bearing these alleles confirmed that the cloned DNA was homologous to
      the genomic OPI1 locus. Furthermore, the OPI1 gene was found to be nonessential
      to the organism since mutants bearing the null allele were viable and exhibited a
      phenotype similar to that of previously isolated opi1 mutants. Similar to other
      opi1 mutants, the opi1 disruption mutants accumulated INO1 mRNA constitutively to
      a level 2-3-fold higher than that observed in wild-type cells. The cloned OPI1
      gene was sequenced, and translation of the open reading frame predicted a protein
      composed of 404 amino acid residues with a molecular weight of 40,036. The
      predicted Opi1 protein contained a well defined heptad repeat of leucine residues
      that has been observed in other regulatory proteins. In addition, the predicted
      protein contained polyglutamine residue stretches which have also been reported
      in yeast genes having regulatory functions. Sequencing of opi1 mutant alleles,
      isolated after chemical mutagenesis, revealed that several were the result of a
      chain termination mutation located within the largest polyglutamine residue
      stretch.

PMID- 1985969
TI  - Cloning, sequencing, and overexpression of genes for ribosomal proteins from
      Bacillus stearothermophilus.
AB  - Although a low resolution model for the arrangement of the proteins of the small
      and large ribosomal subunits is known, a detailed mechanistic understanding of
      the function of the ribosome awaits a high resolution structure of its
      components. While crystals have been obtained of several ribosomal proteins from
      Bacillus stearothermophilus, determination of atomic resolution structures of
      these proteins is impeded by the difficulty of obtaining large amounts of native
      proteins for crystallographic or NMR studies. We describe here the cloning and
      overexpression in Escherichia coli of the genes for ribosomal proteins S5, L6,
      L9, and L18 from B. stearothermophilus. S5 is extremely toxic to E. coli when
      overexpressed, and we have taken advantage of a new tightly regulated expression
      system to obtain high yields (more than 100 mg of pure protein/liter of culture)
      of this protein. The B. stearothermophilus S5 produced in E. coli crystallizes,
      and the crystals are identical to those obtained from the native protein. The
      crystals diffract to 2-A resolution.

PMID- 1985970
TI  - Complete coding sequence and deduced primary structure of the human cartilage
      large aggregating proteoglycan, aggrecan. Human-specific repeats, and additional
      alternatively spliced forms.
AB  - We have obtained the complete coding sequence of the large aggregating
      chondroitin sulfate proteoglycan of human cartilage (aggrecan) from a combination
      of cDNA and genomic exon sequencing. We screened a human costal chondrocyte cDNA
      library, using rat aggrecan cDNA probes, and obtained three nonoverlapping clones
      totaling 6.2 kilobases in length. These clones were sequenced, and the sequence
      of the gaps between clones was obtained from genomic exon fragments and
      polymerase chain reaction-amplified cDNA. The composite sequence is 7137
      nucleotides long, encoding 2316 amino acids. The human and rat aggrecan amino
      acid sequences are about 75% identical, with domains ranging from 100% to about
      60% of conserved amino acids. The human sequence contains two regions of highly
      conserved repeats not found in rat aggrecan: 11 repeats of a hexameric sequence
      in the keratan sulfate attachment domain, E-E-P-(S,F)-P-S; and a 19-amino acid
      sequence reiterated 19 times, in the CS-1 portion of the serine-glycine
      containing region. There are at least three forms of aggrecan transcripts,
      generated by alternative exon usage, and the form reported here is the shortest
      and also the most prevalent, lacking both the epidermal growth factor-like
      domain, and the complement regulatory protein-like sequence.

PMID- 1985971
TI  - Identification of molecular sites on factor VII which mediate its assembly and
      function in the extrinsic pathway activation complex.
AB  - Factor VII-VIIa, in association with tissue factor, participates in the complex
      which initiates blood coagulation through the extrinsic pathway. To identify
      functional domains on factor VII which mediate the activation of factor X, 16
      synthetic peptides corresponding to 55% of the primary structure were assayed for
      their ability to inhibit factor VII function. Factor Xa formation was inhibited
      by eight of the peptides in a dose-dependent manner. Kinetic analyses indicated
      noncompetitive inhibition of factor X activation by seven of these peptides.
      Peptide-(347-361) inhibited factor Xa cleavage of a chromogenic substrate by a
      competitive mechanism and was excluded from further analysis in this study. Among
      the seven inhibitory peptides which have the ability to prevent the factor VIIa
      tissue factor-mediated conversion of factor X to factor Xa, peptide-(285-305) was
      most inhibitory, with a Ki value of 2.4 microM. The Ki values were in the range
      of 42-65 microM for peptides-(44-50), -(194-214), -(208-229), and -(376-390). The
      least inhibitory peptides were at positions 170-178 and 330-340, with a Ki value
      greater than 200 microM. Polyclonal antibodies were raised against four of these
      peptides; and when antisera were assayed by a solid-phase radioimmunoassay, they
      bound not only to their respective immunizing peptides, but also to factor VII.
      The Fab fragments of specific IgG preparations, affinity-purified on a factor VII
      agarose column, inhibited the rate of factor X activation in a dose-dependent
      manner. Six of the seven inhibitory peptides represent amino acid sequences
      within the heavy chain of factor VII, and the remaining one corresponds to a
      sequence within the light chain. The corresponding regions in the x-ray crystal
      structure of chymotrypsin represented by the six heavy chain inhibitory peptides
      are found to be located in three distinct regions, one region located spatially
      distal to the active site and the other two regions located relatively closer to
      the active site and the substrate-binding pocket. The results suggest that at
      least three specific regions in the heavy chain and one region in the light chain
      of factor VII mediate its interaction with the factor X activation complex.

PMID- 1985972
TI  - Three classes of epidermal growth factor receptors on HeLa cells.
AB  - The kinetics of 125I-labeled epidermal growth factor (EGF) binding to receptors
      on HeLa cells were investigated. Scatchard analysis revealed the presence of
      22,000 high affinity receptors (Kd = 0.12 nM) and 25,000 low affinity receptors
      per cell (Kd = 9.2 nM). The kinetic analysis of EGF binding to high affinity
      receptors was performed with cells pretreated with the monoclonal antibody 2E9,
      which prevents specifically EGF binding to low affinity receptors. The study of
      EGF binding to only low affinity receptors was performed with cells pretreated
      with the phorbol ester phorbol 12-myristate 13-acetate, which induces a
      conversion of high affinity receptors to low affinity receptors. This kinetic
      analysis of EGF binding to HeLa cells revealed the presence of three types of
      receptors. High affinity receptors were found to consist of one receptor type
      (type I) with a kinetic association constant (kass) of 6.2 x 10(5) M-1.s-1 and a
      kinetic dissociation constant (kdis) of 3.5 x 10(-4) s-1. The low affinity
      receptors were found to consist of two kinetic distinguishable sites: type II or
      fast sites with kass = 3.3 x 10(6) M-1.s-1 and kdis = 8.1 x 10(-3) s-1 and the
      type III or slow sites with kass = 3.2 x 10(4) M-1.s-1 and kdis = 1.6 x 10(-4) s
      1. The regulatory mechanism which may determine the EGF binding characteristics
      is discussed.

PMID- 1985973
TI  - Molecular cloning and sequence analysis of cDNAs coding for guinea pig alpha 1
      antiproteinases S and F and contrapsin.
AB  - The cDNAs encoding two isoforms, S (slow) and F (fast), of alpha 1-antiproteinase
      (also referred to as alpha 1-antitrypsin or alpha 1-proteinase inhibitor) as well
      as contrapsin were obtained by screening lambda gt11 cDNA library prepared fro
      inflamed guinea pig liver. The sequence analyses of these cDNAs and NH2-terminal
      peptides of the purified proteins revealed that both isoforms of alpha 1
      antiproteinase consist of 405 amino acid residues including a signal peptide of
      24 residues and that contrapsin consists of 410 amino acid residues with the same
      length of the signal peptide. Guinea pig contrapsin had 89, 88, 62, 42, and 41%
      homology to its own alpha 1-antiproteinases F and S, rat alpha 1-antiproteinase,
      mouse and rat contrapsins, respectively. This suggests that guinea pig contrapsin
      is not orthologous to mouse and rat contrapsins and that it developed from a much
      later duplication of alpha 1-antiproteinase gene after the guinea pig had
      diverged from the murine lineage. The available data suggest that the reactive
      site region of alpha 1-antiproteinase can be categorized into orthodox and
      unorthodox types: the former has P3-P'3 consensus sequence of Xaa-Pro-Met-Ser-Xaa
      Pro, where Xaa is Leu, Ile, Val, or Met, while the latter, which occurs in
      species having multiple alpha 1-antiproteinase isoforms, has the sequence whose
      P1 Met has changed to other amino acids. Thus, the reactive site region of the
      orthodox type, which occurs in all seven mammals examined to date, is highly
      conserved. This is in marked contrast to the fact that the same region is
      hypervariable among the paralogous proteins belonging to the serpin superfamily.

PMID- 1985974
TI  - Cooperative interactions between troponin molecules bound to the cardiac thin
      filament.
AB  - Striated muscle thin filaments contain many troponin molecules, which contact
      each other indirectly via tropomyosin and actin. Such allosteric interactions
      between troponin molecules may be responsible for cooperative Ca2+ binding to the
      regulatory sites of the cardiac thin filament (Tobacman, L. S., and Sawyer, D. S.
      (1990) J. Biol. Chem. 265, 931-939). To test whether thin filament-bound troponin
      molecules interact, we studied the competitive binding of troponin and troponin T
      troponin I (an inhibitory complex lacking the Ca2+ binding subunit troponin C) to
      actin-tropomyosin. The relative affinities of these two forms of troponin for the
      thin filament depended upon their relative concentrations. Under conditions where
      total binding was saturated, each form binds with greater apparent affinity to
      sites that have similar neighbors. A theoretical model for competitive binding of
      two ligands to interacting sites on a linear lattice was developed and fit to the
      data. Surprisingly, energetically unfavorable interactions occurred between
      adjacent troponin and troponin T-troponin I molecules not only in the presence of
      Ca2+, but also in the presence of [ethylenebis(oxyethylenenitrilo)]tetraacetic
      acid and/or myosin subfragment 1. Removal of Ca2+ strengthened the affinity of
      troponin for the thin filament less than 50%. These results suggest that, even in
      the absence of myosin, long range allosteric interactions occur between troponin
      molecules. The detailed involvement of tropomyosin and actin in these
      interactions remains to be established.

PMID- 1985975
TI  - Charged residues are major determinants of the transmembrane orientation of a
      signal-anchor sequence.
AB  - Uncleaved signal-anchor sequences of membrane proteins inserted into the
      endoplasmic reticulum initiate the translocation of either the amino-terminal or
      the carboxyl-terminal polypeptide segment across the bilayer. Which topology is
      acquired is not determined by the apolar segment of the signal but rather by the
      hydrophilic sequences flanking it. To study the role of charged residues in
      determining the membrane topology, the insertion of mutants of the
      asialoglycoprotein receptor H1, a single-spanning protein with a cytoplasmic
      amino terminus, was analyzed in transfected COS-7 cells. When the charged amino
      acids flanking the hydrophobic signal were mutated to residues of opposite
      charge, half the polypeptides inserted with the inverted orientation. When, in
      addition, the amino-terminal domain of the mutant protein was truncated,
      approximately 90% of the polypeptides acquired the inverted topology. The
      transmembrane orientation appears to be primarily determined by the charges
      flanking the signal sequence but is modulated by the domains to be translocated.

PMID- 1985976
TI  - Studies on the reaction mechanism of a microbial lipase/acyltransferase using
      chemical modification and site-directed mutagenesis.
AB  - Aeromonas hydrophila releases a protein which is a member of the lipase
      superfamily, similar in reaction mechanism to the important mammalian plasma
      enzyme lecithin-cholesterol acyltransferase. We have used chemical modification
      and site-directed mutagenesis of the protein to identify amino acids which may be
      involved in catalysis. The enzyme was unaffected by phenylmethylsulfonyl
      fluoride, but it was almost completely inhibited by another serine-reactive
      compound, diethyl p-nitrophenyl phosphate. A serine selectively modified by this
      reagent was identified by sequencing the amino-terminal region of the protein. It
      was located at position 16, in the short consensus sequence shared by the enzyme
      with other lipases. When this serine was changed to asparagine the product was an
      enzymatically inert protein which nevertheless retained the surface activity of
      the wild-type enzyme, suggesting its ability to bind to substrate was not
      changed. Diethylpyrocarbonate treatment drastically reduced the rate of acyl
      transfer by the native enzyme, but this did not appear to be due to modification
      of an essential histidine, since inhibition was not reversed by addition of
      hydroxylamine. We have shown that only two of the histidines in the enzyme can be
      involved in catalysis (Hilton, S., McCubbin, W. D., Kay, C.M., and Buckley, J. T.
      (1990) Biochemistry, 29, 9072-9078). Replacing both of these with asparagines had
      little or no effect on enzyme activity. These results indicate that, in apparent
      contrast to other lipases, histidine does not participate in the reaction
      catalyzed by the microbial enzyme. Since catalysis was not inhibited by
      sulfhydryl reagents, we conclude that a free cysteine is also not required for
      activity. This may distinguish the microbial enzyme from the mammalian
      acyltransferase.

PMID- 1985977
TI  - Indications for magnetic resonance imaging.

PMID- 1985978
TI  - T-plasty modification of the Bankart procedure for multidirectional instability
      of the anterior and inferior types.
AB  - Forty patients who had a diagnosis of multidirectional instability of forty-two
      shoulders had a modified Bankart operation in which a T-shaped incision was made
      in the anterior portion of the capsule, with advancement of the inferior flap
      superiorly and of the superior flap medially. All of the patients had been
      injured during athletic activities. Some degree of anterior labral injury was
      present in thirty-eight of the forty-two shoulders. Half of the patients had
      generalized ligamentous laxity. The patients were followed for an average of
      three years (range, two to seven years). Four patients had episodes of
      instability after the operation. Three had a single episode of posterior
      subluxation during throwing, one had recurrent posterior subluxation that
      subsequently was treated by posterior stabilization, and one had anterior
      subluxation while he was diving from a high board. The average loss of external
      rotation after the operation was 5 degrees with the arm at the side and 4 degrees
      with the arm abducted 90 degrees. Satisfaction of the patient was rated excellent
      for forty (95 per cent) of the shoulders, good for one shoulder, and fair for one
      shoulder. However, throwing athletes found that they were unable to throw a ball
      with as much speed as before the operation.

PMID- 1985979
TI  - The clinical value of magnetic resonance imaging in the evaluation of meniscal
      disorders.
AB  - This prospective double-blind study was designed to evaluate the capability of
      magnetic resonance imaging to serve as a diagnostic tool in patients who have a
      clinically suspected disorder of the meniscus. The imaging studies provided a
      diagnostic accuracy of 72 per cent, a sensitivity of 88 per cent, and a
      specificity of 57 per cent. The positive and negative predictive values were 66
      and 83 per cent. The diagnostic sensitivity was 94 per cent for lesions of the
      medial meniscus; this value differed significantly from that of 78 per cent for
      lesions of the lateral meniscus (p less than 0.05). The 37 per cent specificity
      for lesions of the medial meniscus was extremely low compared with the rate of 69
      per cent for lesions of the lateral meniscus (p less than 0.01). In the
      intermediate part of the meniscus, the diagnostic sensitivity was 37 per cent on
      the medial side and 23 per cent on the lateral side; these values were
      significantly less than the average of 74 per cent for the other meniscal
      segments (p less than 0.001). The imaging studies provided an over-all accuracy
      of 67 per cent in the detection of degeneration of the meniscus, 78 per cent in
      the identification of meniscal tears, and 82 per cent in the delineation of
      postoperative lesions.

PMID- 1985980
TI  - Anatomical variations in the course of the superficial peroneal nerve.
AB  - Eighty-five legs in forty-four cadavera were dissected to determine the course of
      the superficial peroneal nerve from its origin to its termination as dorsal
      cutaneous nerves of the foot. Particular attention was paid to the relationship
      of the nerve with the intermuscular septum between the anterior and lateral
      compartments of the leg. In sixty-two (73 per cent) of the legs, the nerve
      coursed within the lateral muscle compartment from its origin to its exit through
      the crural fascia. In twelve (14 per cent) of the legs, the nerve had a variable
      course in the lateral compartment, crossed into the anterior compartment, and
      passed through the fascia. In ten (12 per cent) of the legs, the nerve divided in
      two, with branches in both the anterior and the lateral compartment. In one leg,
      the nerve never lay deep to the peroneus longus but ran along the deep surface of
      the fascia before exiting distally. The nerve or its branches passed through the
      fascia three to eighteen centimeters proximal to the lateral malleolus.

PMID- 1985981
TI  - The effect of a stiff spinal implant on the bone-mineral content of the lumbar
      spine in dogs.
AB  - The response of canine lumbar vertebral bone to the application of a stiff
      transpedicular screw-plate implant from the third to the fifth lumbar vertebra,
      without arthrodesis, was investigated. Five groups of six dogs each were studied:
      dogs that had not had an operation (control group); dogs that had had a sham
      operation, with survival periods of three and six months; and dogs that had
      received an implant, with survival periods of three and six months. The results
      were the same in specimens from the control group and the group that had had a
      sham operation. In the groups that had received an implant, dual-photon
      absorptiometry revealed an insignificant decrease in bone-mineral content at the
      bypassed fourth lumbar segment (17 per cent at three months and 12 per cent at
      six months). When the data for the three and six-month intervals were pooled, the
      mean decrease in bone-mineral content of 14 per cent was significant.
      Histomorphic study yielded similar results; the mean decrease in bone-mineral
      content for the pooled three and six-month specimens was significant (16 per
      cent). Losses were similar for the ventral and dorsal columns. Histomorphometric
      analysis also showed a significant (13 per cent) loss of bone-mineral content at
      the adjacent caudad (sixth lumbar) vertebra for the pooled three and six-month
      groups. The results of the methods of analysis of loss of bone-mineral content
      correlated strongly. Under these experimental conditions, a stiff spinal implant
      caused loss of bone-mineral content of the bypassed vertebral segment, although
      the loss was less than anticipated and did not increase between three and six
      months.

PMID- 1985982
TI  - Coumadin-induced necrosis of the skin after total knee replacement. A case
      report.

PMID- 1985983
TI  - A symptomatic anomalous peroneus brevis in a high-jumper. A case report.

PMID- 1985984
TI  - Aseptic necrosis of the femoral head with a forty-year follow-up. An unusual
      case.

PMID- 1985985
TI  - Post-irradiation femoral neuropathy. A case report.

PMID- 1985986
TI  - Entrapment neuropathy of the suprascapular nerve by a ganglion. A report of three
      cases.

PMID- 1985987
TI  - Absorbable implants for the fixation of fractures.

PMID- 1985988
TI  - Septic arthritis of the shoulder in adults.

PMID- 1985989
TI  - Prophylaxis with indomethacin for heterotopic bone after open reduction of
      fractures of the acetabulum.

PMID- 1985990
TI  - Magnetic resonance imaging of the shoulder. Sensitivity, specificity, and
      predictive value.
AB  - The sensitivity, specificity, and predictive value of magnetic resonance imaging
      in the diagnosis of lesions of the rotator cuff, glenohumeral capsule, and
      glenoid labrum were evaluated in ninety-one patients and fifteen asymptomatic
      volunteers. Magnetic resonance imaging demonstrated 100 per cent sensitivity and
      95 per cent specificity in the diagnosis of complete tears, and it consistently
      predicted the size of the tear of the rotator cuff. There was a definite
      correlation between atrophy of the supraspinatus muscle and the size of a
      complete, chronic tear of the rotator cuff. The sensitivity and specificity of
      magnetic resonance imaging in the differentiation of tendinitis from degeneration
      of the cuff were 82 and 85 per cent, and in the differentiation of a normal
      tendon from one affected by tendinitis with signs of impingement the sensitivity
      and specificity were 93 and 87 per cent. The formation of spurs around the
      acromion and acromiocalvicular joint correlated highly with increased age of the
      patient and with chronic disease of the rotator cuff. The sensitivity and
      specificity of magnetic resonance imaging in the diagnosis of labral tears
      associated with glenohumeral instability were 88 and 93 per cent. The study
      showed that high-resolution magnetic-resonance imaging is an excellent non
      invasive tool in the diagnosis of lesions of the rotator cuff and glenohumeral
      instability.

PMID- 1985992
TI  - Tests for posterolateral instability of the knee in normal subjects. Results of
      examination under anesthesia.
AB  - An apparently normal knee was examined in each of 100 subjects while they were
      under general or epidural anesthesia for an unrelated operation. The Lachman,
      anterior drawer, posterior drawer, and pivot-shift tests were negative in all
      knees. All knees were stable to varus and valgus stress at both 0 and 30 degrees
      of flexion. The external-rotation recurvatum test also was negative in all knees.
      A positive reversed pivot-shift sign was present in 35 per cent of the knees,
      suggesting that it may not signify abnormality, at least not without a negative
      test on the contralateral knee. The results of the posterolateral drawer test
      were variable, difficult to quantify, and did not always have a firm end-point.
      The amount of maximum external rotation of the tibia, measured from the reference
      line of the medial border of the foot, was extremely variable at both 30 and 90
      degrees of flexion of the knee. External rotation, as determined by this
      reference, was slightly greater (averaging 9 degrees) at 90 than at 30 degrees of
      flexion. The normal range of maximum external rotation of the foot was 10 to 45
      degrees at 30 degrees of flexion of the knee and 15 to 70 degrees at 90 degrees
      of flexion. The presence of a large angle of external rotation and a positive
      reversed pivot-shift sign correlated strongly with increased ligamentous laxity
      and mild varus alignment of the knee.

PMID- 1985991
TI  - Accuracy of diagnoses from magnetic resonance imaging of the knee. A multi-center
      analysis of one thousand and fourteen patients.
AB  - Magnetic resonance images of the knee were made for 1014 patients, and the
      diagnosis was subsequently confirmed arthroscopically. The accuracy of the
      diagnoses from the imaging was 89 per cent for the medial meniscus, 88 per cent
      for the lateral meniscus, 93 per cent for the anterior cruciate ligament, and 99
      per cent for the posterior cruciate ligament. The magnetic resonance examinations
      were done at several centers, and the results varied substantially among centers.
      The accuracy ranged from 64 to 95 per cent for the medial meniscus, from 83 to 94
      per cent for the lateral meniscus, and from 78 to 97 per cent for the anterior
      cruciate ligament. The results from different magnetic-resonance units were also
      compared, and the findings suggested increased accuracy for the units that had a
      stronger magnetic field. Of the menisci for which the magnetic resonance signal
      was reported to be Grade II (a linear intrameniscal signal not extending to the
      superior or inferior meniscal surface), 17 per cent were found to be torn at
      arthroscopy.

PMID- 1985994
TI  - Carpometacarpal dislocations. Long-term follow-up.
AB  - Twenty patients who had a dislocation of one or all of the medial four
      carpometacarpal joints were followed for an average of 6.5 years (range, 1.5 to
      20.5 years). Fifteen patients were treated with open reduction and internal
      fixation during the first three weeks after injury and the long-term result was
      excellent in thirteen of them. Three of the four unsatisfactory results were in
      patients who had injuries to the normally rigid second and third carpometacarpal
      joints or had a concomitant ulnar-nerve injury.

PMID- 1985993
TI  - Skeletal involvement in children who have chronic granulomatous disease.
AB  - Chronic granulomatous disease is a rare disorder of the oxidative metabolism of
      the white blood cells that results in immunodeficiency. In a retrospective review
      of the records of forty-two patients who had chronic granulomatous disease, we
      identified thirteen patients who had a total of twenty skeletal infections. Two
      types of infection were noted: Type 1, which resulted from a direct spread of the
      infection from an adjacent focus, usually of fungus or mycobacteria, and Type 2,
      which resulted from hematogenous spread, usually of Nocardia or more common
      bacteria. The thoracic vertebrae, ribs, and metatarsals were the most commonly
      involved bones. All four patients in whom the vertebrae were involved had a Type
      1 fungal infection. Paresis developed in three of these patients, and two of them
      died. Antibiotics alone effectively eradicated the infection in only one patient.
      Wide operative debridement combined with administration of antibiotics was the
      most successful treatment. Comprehensive preoperative imaging and several
      cultures are necessary to locate the infection in the bone and to identify the
      organism.

PMID- 1985995
TI  - Posterior transfer of the adductors in children who have cerebral palsy. A long
      term study.
AB  - Seventy-eight posterior transfers of the adductors of the hip in forty-two
      children who has spastic cerebral palsy were reviewed an average of 5.7 years
      after the operation (range, two to 14.6 years). The results were assessed on the
      basis of the patient's ability to walk, the range of motion of the affected hip
      or hips, and the radiographic measurements. In 88 per cent of the patients, the
      transfer was successful in improving or maintaining abduction, extension,
      functional walking, and stability of the hip. The failures were all in patients
      who were unable to walk and who had spastic quadriplegia. Tenotomy of the
      iliopsoas tendon at the time of the transfer procedure resulted in an improved
      range of motion of the hip.

PMID- 1985997
TI  - Use of autologous blood in total hip replacement. A comprehensive program.
AB  - We evaluated the effectiveness of a comprehensive program for the use of
      autologous blood in reduction of the need for transfusion of homologous blood in
      total hip replacement in a prospective study of a consecutive series of patients.
      Transfusion of homologous blood was minimized through transfusion of
      preoperatively deposited autologous blood, intraoperative and postoperative
      salvage of washed red blood cells, and use of the clinical condition of the
      patient as the sole criterion for transfusion of non-autologous blood, regardless
      of the hematocrit. The cases of 143 patients who had had 154 primary total hip
      replacements were studied. One hundred and forty-three procedures were done on
      patients who had not been prevented from donating blood for medical reasons, and
      93 per cent of these 143 procedures were performed with the availability of one
      to five units of preoperatively deposited autologous blood. The patients
      predeposited an average of 2.6 units of blood for each procedure. Ninety-two per
      cent of the procedures for which autologous blood had been predeposited were
      performed without transfusion of homologous blood. In the entire group of
      patients, almost 90 per cent of the transfused blood was autologous blood.
      Intraoperative salvage of red blood cells was successful in 148 procedures, and
      salvage was continued in the recovery room for all of these patients. An average
      of 408 milliliters of red blood cells was saved and reinfused, and this was 28
      per cent of the average total loss of blood (1435 milliliters) for this series of
      procedures.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1985996
TI  - Healing of digital flexor tendons: importance of the interval from injury to
      repair. A biomechanical, biochemical, and morphological study in dogs.
AB  - The effect of an elapsed interval of time between injury and operative repair of
      the flexor tendons was investigated in a canine model. Transected intrasynovial
      flexor tendons were repaired either immediately or after a delay of seven or
      twenty-one days. The biomechanical, biochemical, and morphological
      characteristics were compared at three and six weeks. The values for angular
      rotation, linear excursion, ultimate load, and linear slope were determined;
      concentrations of collagen and reducible collagen cross-links, an index of newly
      synthesized collagen, were measured; and the ultrastructural morphology of the
      tendons was examined by high-voltage electron microscopy. For the tendons that
      were repaired immediately, the values for angular rotation were 9.4 +/- 3.2 and
      13.0 +/- 3.7 degrees at three and six weeks; for those that were repaired at
      seven days, 4.1 +/- 1.3 and 2.5 +/- 1.4 degrees; and for those that were repaired
      at twenty-one days, 2.7 +/- 0.8 and 4.7 +/- 0.7 degrees. There was a significant
      effect of the delay until repair on the angular rotation and linear excursion in
      all three groups (p less than 0.005 for both). Tensile testing of the bone-tendon
      complex revealed no significant effect of the delay on the values for ultimate
      load (p greater than 0.05). There were no significant differences in total
      concentration of collagen at the sites of repair or in the levels of reducible
      Schiff-base cross-links (indicators of newly synthesized cross-links) in tendons
      from the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1985998
TI  - Deformities of the hip in adults who have sickle-cell disease and had avascular
      necrosis in childhood. A natural history of fifty-two patients.
AB  - We report the natural course of the hip in fifty-two patients (ninety-five hips)
      who had sickle-cell disease and had had avascular necrosis in childhood. There
      were twenty-one African, twenty-one West Indian, and ten Mediterranean patients.
      At the most recent follow-up examination (at an average duration of nineteen
      years after the onset of the disease), 80 per cent of the hips that had been
      affected by avascular necrosis during childhood were painful and had permanent
      damage with regard to decreased mobility, limb-length discrepancy, and an
      abnormal gait. When the patients were evaluated, at an average age of thirty-one
      years, fifteen hips (16 per cent) had had an operation for progressive disability
      and sixty (63 per cent) had major problems because of pain. Of the twenty hips
      (21 per cent) that were not painful, five were in patients who had an abnormal
      gait, with decreased agility. The mean Iowa hip-rating score at the most recent
      follow-up examination was 73 points (range, 30 to 100 points). Correlations were
      found between the hip score and the patient's age at the onset of the disease and
      at the latest follow-up, between the hip score and degenerative changes in the
      hip, and between degenerative changes and radiographic evidence of deformity of
      the hip.

PMID- 1985999
TI  - Ingrowth and formation of bone in defects in an uncemented fiber-metal total hip
      replacement model in dogs.
AB  - An osseous defect was created in the acetabulum and femur of twenty dogs, and
      then a fiber-metal total hip prosthesis was inserted. A comparison was made
      between the effects of leaving the defects unfilled, filling the defects with an
      autogenous bone graft, and filling them with a 50:50 mixture of autogenous bone
      graft and a biphasic ceramic composed of hydroxyapatite and tricalcium phosphate.
      The characteristics of formation of bone within the sites of the defects and the
      extent of the ingrowth of bone into the underlying porous surface were analyzed.
      At six and twelve weeks after implantation, the dogs in the control group
      (unfilled defects) had the least amount of bone in the sites of the defects. In
      the dogs that had had an autogenous bone graft and those in which the defects had
      been filled with a mixture of autogenous bone graft and biphasic ceramic, there
      were excellent osteoconductive properties in the filling of the sites of the
      defects with new bone. A comparison was made between the amount of bone that
      formed in the osseous defects and the amount that formed in the spaces of the
      porous-surfaced fiber-metal components of the prostheses, directly underlying and
      adjacent to the defects. At six weeks, the greatest amount of ingrowth of bone
      into the spaces of the underlying titanium fiber-metal acetabular components was
      seen in the control group (22 per cent of the porous surface), followed by the
      group in which the defects had been filled with a mixture of autogenous bone
      graft and biphasic ceramic (19 per cent). The defects that had been filled only
      with autogenous bone graft had poor ingrowth of bone into the porous surface (4
      per cent) and predominantly fibrous ingrowth. At twelve weeks, these defects
      again showed the least amount of ingrowth of bone (15 per cent) compared with the
      defects in the control group (24 per cent) and those that had been filled with a
      mixture of autogenous bone graft and biphasic ceramic (24 per cent). No
      statistically significant differences were found in the amount of ingrowth of
      bone into the defects that had been created in the femur in the three groups of
      dogs at either six or twelve weeks. However, the trends appeared to correlate
      with the data for the acetabular defects.

PMID- 1986000
TI  - A Ca2+ transport system associated with the plasma membrane of Dictyostelium
      discoideum is activated by different chemoattractant receptors.
AB  - Amebae of Dictyostelium exhibit a transient uptake of extracellular Ca2+
      approximately 5 s after activation of surface folate or cAMP receptors (Bumann,
      J., B. Wurster, and D. Malchow. 1984. J. Cell Biol. 98:173-178). To further
      characterize these Ca2+ entry systems, we analyzed 45Ca2+ uptake by resting and
      activated amebae. Like the surface chemoreceptors, folate- and cAMP-induced Ca2+
      uptake responses were developmentally regulated; the former response was evident
      in vegetative but not aggregation-competent cells, whereas the latter response
      displayed the opposite pattern of expression. In contrast, other characteristics
      of these Ca2(+)-uptake pathways were remarkably similar. Both systems (a)
      exhibited comparable kinetic properties, (b) displayed a high specificity for
      Ca2+, and (c) were inhibited effectively by Ruthenium Red, sodium azide, and
      carbonylcyanide m-chlorophenyl-hydrazone. These results, together with the
      finding that vegetative cells transformed with a plasmid expressing the surface
      cAMP receptor exhibit a cAMP-induced Ca2+ uptake, suggest that different
      chemoreceptors activate a single Ca2+ entry pathway. Additional pharmacological
      and ion competition studies indicated that receptor-mediated Ca2+ entry probably
      does not involve a Na+/Ca2+ exchanger or voltage-activated channels.
      Chemoattractant binding appears to generate intracellular signals that induce
      activation and adaption of the Ca2(+)-uptake response. Analysis of putative
      signaling mutants suggests that Ca2+ entry is not regulated by the guanine
      nucleotide-binding (G) protein subunits G alpha 1 or G alpha 2, or by G protein
      mediated changes in intracellular cAMP or guanosine 3,'5'-cyclic monophosphate
      (cGMP).

PMID- 1986001
TI  - Contrasting expression patterns of three members of the myc family of
      protooncogenes in the developing and adult mouse kidney.
AB  - The myc family of protooncogenes encode similar but distinct nuclear proteins.
      Since N-myc, c-myc, and L-myc have been found to be expressed in the newborn
      kidney, we studied their expression during murine kidney development. By organ
      culture studies and in situ hybridization of tissue sections, we found that each
      of the three members of the myc gene family shows a remarkably distinct
      expression pattern during kidney development. It is known that mesenchymal stem
      cells of the embryonic kidney convert into epithelium if properly induced. We
      demonstrate the N-myc expression increases during the first 24 h of in vitro
      culture as an early response to induction. Moreover, the upregulation was
      transient and expression levels were already low during the first stages of overt
      epithelial cell polarization. In contrast, neither c-myc nor L-myc were
      upregulated by induction of epithelial differentiation. c-myc was expressed in
      the uninduced mesenchyme but subsequently became restricted to the newly formed
      epithelium and was not expressed in the surrounding loose mesenchyme. At onset of
      terminal differentiation c-myc expression was turned off also from the epithelial
      tubules. We conclude that N-myc is a marker for induction and early epithelial
      differentiation states. That the undifferentiated mesenchyme, unlike stromal
      cells of later developmental stages, express c-myc demonstrates that the
      undifferentiated mesenchymal stem cells are distinct from the stromal cells. The
      most astonishing finding, however, was the high level of L-myc mRNA in the
      ureter, ureter-derived renal pelvis, papilla, and collecting ducts. In the
      ureter, expression increased, rather than decreased, with advancing maturation
      and was highest in adult tissue. Our results suggest that each of the three
      members of the myc gene family are involved in quite disparate differentiation
      processes, even within one tissue.

PMID- 1986002
TI  - Dystrophin-glycoprotein complex is highly enriched in isolated skeletal muscle
      sarcolemma.
AB  - mAbs specific for protein components of the surface membrane of rabbit skeletal
      muscle have been used as markers in the isolation and characterization of
      skeletal muscle sarcolemma membranes. Highly purified sarcolemma membranes from
      rabbit skeletal muscle were isolated from a crude surface membrane preparation by
      wheat germ agglutination. Immunoblot analysis of subcellular fractions from
      skeletal muscle revealed that dystrophin and its associated glycoproteins of 156
      and 50 kD are greatly enriched in purified sarcolemma vesicles. The purified
      sarcolemma was also enriched in novel sarcolemma markers (SL45, SL/TS230) and
      Na+/K(+)-ATPase, whereas t-tubule markers (alpha 1 and alpha 2 subunits of
      dihydropyridine receptor, TS28) and sarcoplasmic reticulum markers (Ca2(+)
      ATPase, ryanodine receptor) were greatly diminished in this preparation. Analysis
      of isolated sarcolemma by SDS-PAGE and densitometric scanning demonstrated that
      dystrophin made up 2% of the total protein in the rabbit sarcolemma preparation.
      Therefore, our results demonstrate that although dystrophin is a minor muscle
      protein it is a major constituent of the sarcolemma membrane in skeletal muscle.
      Thus the absence of dystrophin in Duchenne muscular dystrophy may result in a
      major disruption of the cytoskeletal network underlying the sarcolemma in
      dystrophic muscle.

PMID- 1986003
TI  - Formation of hemidesmosomes in vitro by a transformed rat bladder cell line.
AB  - Two hemidesmosomal plaque components of 230 and 180 kD have recently been
      characterized using autoantibodies in the serum samples of bullous pemphigoid
      (BP) patients (Klatte, D. H., M. A. Kurpakus, K. A. Grelling, and J. C. R. Jones.
      1989, J. Cell Biol. 109:3377-3390). These BP autoantibodies generate the type of
      staining patterns that one would predict for formed hemidesmosomes, i.e., a
      punctate staining pattern towards the substratum; in less than 50% of various
      primary epithelial and transformed epidermal cell lines even when such cells are
      maintained in culture for prolonged periods. In contrast, affinity-purified human
      autoantibodies against the 230-kD hemidesmosomal plaque component generate
      intense immunofluorescence staining along the region of cell-substratum
      interaction in the rat bladder tumor cell line 804G maintained on uncoated glass
      cover-slips. This pattern is distinct from that observed in the 804G cells using
      an antibody preparation directed against vinculin, a component of adhesion
      plaques. Ultrastructural analyses of the 804G cells reveals that hemidesmosome
      like structures occur along the basal surface of cells where they abut the
      substratum. These structures are present in 804G cells maintained in culture in
      reduced levels of Ca2+ and are recognized by autoantibodies directed against the
      230-kD hemidesmosomal plaque component as determined by immunogold
      ultrastructural localization. To study hemidesmosome appearance in this cell
      line, 804G cells were trypsinized and then allowed to readhere to glass
      coverslips. In rounded, unattached 804G cells, hemidesmosome-like plaque
      structures occur along the cell surface. These structures are recognized by the
      230-kD autoantibodies. At 1 h after plating, hemidesmosomes are observed along
      the substratum attached surface of cells. Protein synthesis is not required for
      the appearance of these hemidesmosomes. Within 4 h of plating, autoantibody
      staining and hemidesmosomes appear towards the cell periphery. Subsequently, the
      polypeptide recognized by the BP autoantibodies becomes concentrated in the
      perinuclear region, where there are numerous hemidesmosomes. We propose that the
      hemidesmosomes in 804G cells are involved in cell-substratum adhesion. We discuss
      possible mechanisms of assembly of hemidesmosomes in the 804G cells. Indeed, the
      804G cells should prove an invaluable cell line for the biochemical and molecular
      dissection of hemidesmosome structure, function, and assembly.

PMID- 1986004
TI  - Receptor functions for the integrin VLA-3: fibronectin, collagen, and laminin
      binding are differentially influenced by Arg-Gly-Asp peptide and by divalent
      cations.
AB  - The capability of the integrin VLA-3 to function as a receptor for collagen
      (Coll), laminin (Lm), and fibronectin (Fn) was addressed using both whole cell
      adhesion assays and ligand affinity columns. Analysis of VLA-3-mediated cell
      adhesion was facilitated by the use of a small cell lung carcinoma line (NCI
      H69), which expresses VLA-3 but few other integrins. While VLA-3 interaction with
      Fn was often low or undetectable in cells having both VLA-3 and VLA-5, NCI-H69
      cells readily attached to Fn in a VLA-3-dependent manner. Both Arg-Gly-Asp (RGD)
      peptide inhibition studies, and Fn fragment affinity columns suggested that VLA
      3, like VLA-5, may bind to the RGD site in human Fn. However, unlike Fn, both
      Coll and Lm supported VLA-3-mediated adhesion that was not inhibited by RGD
      peptide, and was totally unaffected by the presence of VLA-5. In addition, VLA-3
      mediated binding to Fn was low in the presence of Ca++, but was increased 6.6
      fold with Mg++, and 30-fold in the presence of Mn++. In contrast, binding to Coll
      was increased only 1.2-fold with Mg++, and 1.7-fold in Mn++, as compared to the
      level seen with Ca++. Together, these experiments indicate that VLA-3 can bind
      Coll, Lm, and Fn, and also show that (a) VLA-3 can recognize both RGD-dependent
      and RGD-independent ligands, and (b) different VLA-3 ligands have distinctly
      dissimilar divalent cation sensitivities.

PMID- 1986005
TI  - Localization of components involved in protein transport and processing through
      the yeast Golgi apparatus.
AB  - Saccharomyces cerevisiae sec7 mutants exhibit pleiotropic deficiencies in the
      transit of proteins through the Golgi apparatus, and elaborate an array of Golgi
      apparatus-like cisternae at a restrictive growth temperature (37 degrees C). The
      SEC7 gene encodes an essential high-molecular weight protein (227 kD) that is
      phosphorylated in vivo. In cell lysates, Sec7 protein (Sec7p) is recovered in
      both sedimentable and soluble fractions. A punctate immunofluorescent pattern of
      Sec7p-associated structures seen in SEC cells coalesces in sec14 mutant yeast
      that accumulate exaggerated Golgi cisternae at 37 degrees C. Sec7p may function
      as a peripheral membrane protein that cycles between a soluble, cytosolic pool
      and a sedimentable, membrane-associated complex for its essential role in
      vesicular traffic through the Golgi apparatus. The transmembrane Kex2 protease,
      which processes precursors of secreted peptides within the yeast secretory
      pathway, is also localized by indirect immunofluorescence to multiple structures
      in the yeast cell (Redding, K., and R. Fuller, manuscript submitted for
      publication). In double-immunofluorescence labeling experiments, significant
      colocalization of Sec7 and Kex2 proteins was found. Colocalization of the two
      antigens, one implicated in protein transport through the Golgi apparatus and the
      other in processing within a late Golgi compartment, supports the conclusion that
      we have visualized the yeast Golgi apparatus.

PMID- 1986008
TI  - Magnetic resonance imaging in hypopituitarism.

PMID- 1986006
TI  - Reconstitution of constitutive secretion using semi-intact cells: regulation by
      GTP but not calcium.
AB  - Regulated exocytosis in many permeabilized cells can be triggered by calcium and
      nonhydrolyzable GTP analogues. Here we examine the role of these effectors in
      exocytosis of constitutive vesicles using a system that reconstitutes transport
      between the trans-Golgi region and the plasma membrane. Transport is assayed by
      two independent methods: the movement of a transmembrane glycoprotein (vesicular
      stomatitis virus glycoprotein [VSV G protein]) to the cell surface; and the
      release of a soluble marker, sulfated glycosaminoglycan (GAG) chains, that have
      been synthesized and radiolabeled in the trans-Golgi. The plasma membrane of CHO
      cells was selectively perforated with the bacterial cytolysin streptolysin-O.
      These perforated cells allow exchange of ions and cytosolic proteins but retain
      intracellular organelles and transport vesicles. Incubation of the semi-intact
      cells with ATP and a cytosolic fraction results in transport of VSV G protein and
      GAG chains to the cell surface. The transport reaction is temperature dependent,
      requires hydrolyzable ATP, and is inhibited by N-ethylmaleimide. Nonhydrolyzable
      GTP analogs such as GTP gamma S, which stimulate the fusion of regulated
      secretory granules, completely abolish constitutive secretion. The rate and
      extent of constitutive transport between the trans-Golgi and the plasma membrane
      is independent of free Ca2+ concentrations. This is in marked contrast to fusion
      of regulated secretory granules with the plasma membrane, and transport between
      the ER and the cis-Golgi (Beckers, C. J. M., and W. E. Balch. 1989. J. Cell Biol.
      108:1245-1256; Baker, D., L. Wuestehube, R. Schekman, and D. Botstein. 1990.
      Proc. Natl. Acad. Sci. USA. 87:355-359).

PMID- 1986007
TI  - Recycling of epidermal growth factor-receptor complexes in A431 cells:
      identification of dual pathways.
AB  - The intracellular sorting of EGF-receptor complexes (EGF-RC) has been studied in
      human epidermoid carcinoma A431 cells. Recycling of EGF was found to occur
      rapidly after internalization at 37 degrees C. The initial rate of EGF recycling
      was reduced at 18 degrees C. A significant pool of internalized EGF was incapable
      of recycling at 18 degrees C but began to recycle when cells were warmed to 37
      degrees C. The relative rate of EGF outflow at 37 degrees C from cells exposed to
      an 18 degrees C temperature block was slower (t1/2 approximately 20 min) than the
      rate from cells not exposed to a temperature block (t1/2 approximately 5-7 min).
      These data suggest that there might be both short- and long-time cycles of EGF
      recycling in A431 cells. Examination of the intracellular EGF-RC dissociation and
      dynamics of short- and long-time recycling indicated that EGF recycled as EGF-RC.
      Moreover, EGF receptors that were covalently labeled with a photoactivatable
      derivative of 125I-EGF recycled via the long-time pathway at a rate similar to
      that of 125I-EGF. Since EGF-RC degradation was also blocked at 18 degrees C, we
      propose that sorting to the lysosomal and long-time recycling pathway may occur
      after a highly temperature-sensitive step, presumably in the late endosomes.

PMID- 1986009
TI  - Nature of altered growth hormone secretion in hyperthyroidism.
AB  - Hyperthyroidism is accompanied by various neuroendocrine regulatory disturbances
      that affect not only the thyrotropic, but also the gonadotropic, corticotropic,
      and somatotropic axes. To examine the nature of alterations in neuroendocrine
      control mechanisms that direct the somatotropic axis in hyperthyroidism, we have
      applied a novel deconvolution technique designed to estimate the number,
      amplitude, and mass of significant underlying GH secretory events after the
      influence of GH metabolic clearance has been removed mathematically. To this end,
      blood was sampled at 10-min intervals for 24 h in seven hyperthyroid and seven
      age-matched euthyroid men. The subsequent GH time series were assayed by
      immunoradiometric assay (sensitivity, 0.08 ng/mL) and submitted to quantitative
      deconvolution analysis. We found that hyperthyroid compared to euthyroid men 1)
      had significantly more GH secretory bursts per 24 h (viz. 15 +/- 1.0 vs. 10 +/-
      1.1; P = 0.017); 2) secreted 3 times as much GH per burst (3.7 +/- 0.80 vs. 1.3
      +/- 0.42 ng/mL distribution vol; P = 0.013); 3) achieved a maximal rate of GH
      secretion in each burst 2.3-fold higher than that in control men (0.14 +/- 0.028
      vs. 0.060 +/- 0.015 ng/mL.min; P = 0.017); and 4) had 3.7-fold higher 24-h
      endogenous GH production rates (P less than 0.01). Neither hyperthyroid nor
      euthyroid men had significant interburst (tonic) GH secretion. We conclude that
      the somatotropic axis in hyperthyroid men is marked by a higher frequency of
      spontaneous GH secretory bursts, a higher rate of maximal GH secretion attained
      per burst, and a larger mass of GH released per burst. These neuroregulatory
      disturbances result in a nearly 4-fold increase in the 24-h production rate of GH
      in thyrotoxicosis.

PMID- 1986010
TI  - Stimulation of glucagon secretion by gastric inhibitory polypeptide in patients
      with hepatic cirrhosis and hyperglucagonemia.
AB  - Porcine gastric inhibitory polypeptide (GIP) was infused iv (120 micrograms in 60
      min) in seven patients with biopsy-proven hepatic cirrhosis who had surgical
      porta-caval anastomoses and hyperglucagonemia in the postabsorptive state. The
      infusions resulted in elevation of blood levels of immunoreactive GIP into the
      upper range of those observed after ingestion of large mixed meals. This was
      accompanied by significant increments in immunoreactive glucagon (IRG) in the
      plasma. Similar infusions in two cirrhotic patients with surgical porta-caval
      anastomoses who had normal plasma IRG levels in the postabsorptive state had no
      effect on the plasma IRG level. Ingestion of triglyceride (60 g) in
      hyperglucagonemic cirrhotic patients with porta-caval anastomoses also resulted
      in elevation of plasma immunoreactive GIP, and this was again associated with
      significant elevation of the plasma IRG level. Chromatography studies showed that
      the increments in plasma IRG after the administration of GIP or triglyceride were
      largely accounted for by increases in pancreatic-type glucagon. There were no
      significant effects of administration of GIP or triglyceride on the blood levels
      of glucose or immunoreactive insulin. It is concluded that porcine GIP is
      glucagonotropic in patients with cirrhosis of the liver who show elevated levels
      of IRG in the plasma in the postabsorptive state. This effect is not due to
      diversion of portal blood to the systemic circulation and may be attributable to
      hypersensitivity of the alpha-cells to stimulation by GIP.

PMID- 1986011
TI  - Influence of fasting and refeeding on 3,3',5'-triiodothyronine metabolism in man.
AB  - To determine the influence of prolonged fasting and refeeding on rT3 metabolism
      in man, five euthyroid obese subjects underwent a 13-day fast, followed by a
      refeeding period. Each patient received an iv dose of 25 muCi [125I]rT3 during
      the fed control period, on days 7 and 13 of the fast, and on the fourth day after
      refeeding with a regular diet. Serial blood and urine samples were obtained to
      determine serum rT3 clearance and production rates and the urinary tracer rT3
      deiodination fraction. Significant increases in serum rT3 values were noted by
      day 7 and remained elevated for the duration of the fast (P less than 0.01).
      Normalization of rT3 levels occurred after 4 days of refeeding. Both 7 and 13
      days of fasting decreased rT3 clearance [132.6 +/- 8.3 L/day (P less than 0.001)
      and 132.2 +/- 9.5 L/day (P less than 0.001), respectively] without changing rT3
      production (36.8 +/- 5.3 and 33.0 +/- 3.7 nmol/D, respectively) compared to
      control values (207.0 +/- 10.9 L/day and 31.8 +/- 3.8 nmol/day, respectively).
      Refeeding did not restore rT3 clearance (151.2 +/- 6.9 L/day; P less than 0.002),
      but significantly reduced blood rT3 production (18.4 +/- 3.8 nmol/day; P less
      than 0.003). The fractional deiodination of rT3 was significantly reduced on day
      7 (42.5 +/- 4.6%; P less than 0.01) and day 13 (41.9 +/- 3.7%; P less than 0.01)
      of fasting compared to the control value (69.2 +/- 2.8%), while refeeding only
      partially restored deiodination to baseline (48.4 +/- 5.1%; P less than 0.04).
      The clearance of rT3 was highly dependent on the fractional deiodination rate (r
      = 0.83; P less than 0.001). Although rT3 production remained constant during
      fasting, reduced rT3 production was seen on the fourth day of refeeding. This
      unique observation explained the fall in serum rT3 to prefasting levels after 4
      days of refeeding when rT3 clearance was still inhibited. This study, in context
      with previous investigations, indicates that T4 conversion to circulating T3 and
      rT3 in fasting is a highly complex and multifaceted process requiring further
      investigation to elucidate the mechanism responsible for these alterations.

PMID- 1986012
TI  - Free fatty acids do not influence the concentrations of free steroid hormones in
      serum under physiological conditions.
AB  - In several recent studies it has been suggested that FFA may influence the
      concentrations of unbound steroid hormones in serum, but the experimental design
      of these studies has been questioned. We have reexamined the effects of oleic
      acid on the unbound concentrations of several steroid hormones in serum,
      including cortisol, testosterone, and estradiol. The results demonstrate that
      under physiological conditions, oleic acid does not affect the unbound
      concentrations of these hormones when assays are carried out with whole serum.

PMID- 1986013
TI  - Systemic mastocytosis presenting as osteoporosis: a clinical and
      histomorphometric study.
AB  - Ten patients with systemic mastocytosis (SM) were evaluated for their metabolic
      bone disease (4 men and 6 women; mean +/- SD, 59 +/- 13 yr). All patients
      presented with generalized osteopenia and/or atraumatic vertebral compression
      fractures. Three patients had long-standing urticaria pigmentosa; in these, the
      diagnosis of cutaneous mastocytosis had been established by skin biopsy. One of
      the 3 and 2 of the other 7 individuals had symptoms suggestive of SM. Although
      six patients had previously undergone decalcified bone marrow trephine core
      biopsy (DBMB), findings were consistent with SM in only 2 of them. X-Ray survey
      revealed generalized osteopenia in all 10 patients and vertebral compression
      fractures in 9. No patient had sclerotic bone lesions. Histological findings of
      undecalcified transiliac crest biopsy (UTBB) specimens from 9 patients (5
      patients underwent both DBMB and UTBB, 4 underwent only UTBB, and 1 had only
      DBMB) disclosed bone marrow that contained nodules characteristic of mast cell
      granulomas and numerous scattered oval- and spindle-shaped mast cells. The
      trabecular bone contained abundant newly synthesized bone matrix and a
      significant increase in osteoblastic, osteoclastic, and resorptive surfaces.
      Dynamic histomorphometric parameters revealed a significantly increased mineral
      apposition rate. Our study suggests that SM may be a more frequent cause of
      osteoporosis than previously recognized. Generalized osteopenia with compression
      fractures may be the only presentation of SM. Undecalcified bone biopsy is useful
      in the diagnosis of SM. Accelerated bone remodeling is a characteristic
      histomorphometric feature of SM with diffuse osteopenia.

PMID- 1986014
TI  - Acceleration of luteinizing hormone pulse frequency in functional hypothalamic
      amenorrhea by dopaminergic blockade.
AB  - A constellation of neuroendocrine secretory aberrations, including reduced LH
      pulse frequency and PRL concentrations, has been documented in women with
      functional hypothalamic amenorrhea (FHA). As pituitary function was preserved,
      these aberrations were attributed to an alteration in hypothalamic
      neuromodulation. To investigate the participation of the dopaminergic system in
      the genesis of the reduced LH pulse frequency and suppressed PRL levels in FHA,
      we studied six women with FHA and six cyclic women in the early follicular phase
      by obtaining blood samples at 15-min intervals for 48 h during sequential 24-h
      infusions of saline and a dopamine receptor blocker, metoclopramide (MCP). A
      hypothalamic vs. pituitary site of action was inferred from the pulsatility
      characteristics. MCP consistently elicited an increase in the LH pulse frequency
      in the women with FHA [7.3 +/- 1.2 (+/- SE) to 10.5 +/- 1.3 pulses/24 h; P less
      than 0.005]. In contrast, the eumenorrheic women did not show a significant
      change in LH pulse frequency in response to MCP (15.2 +/- 1.0 to 14.3 +/- 0.9
      pulses/24 h). While the PRL concentrations were significantly lower in the FHA
      group during the infusion of saline (P less than 0.001) and MCP (P less than
      0.005), the relative increases in PRL during MCP were similar in both groups. The
      acceleration of LH pulse frequency by blockade of dopamine receptors implies that
      there is increased hypothalamic dopaminergic inhibition of GnRH pulse frequency
      in women with FHA.

PMID- 1986015
TI  - Extrarenal production of calcitriol in normal and uremic humans.
AB  - We have previously reported low serum levels of 1,25-dihydroxyvitamin D3 [1,25
      (OH)2D3] and increased 1,25-(OH)2D3 production after the administration of 25
      hydryoxyvitamin D (25OHD) to anephric humans. Since normal alveolar macrophages
      are known to synthesize 1,25-(OH)2D3 when stimulated with gamma-interferon or
      lipopolysaccharide, we determined whether macrophages derived from peripheral
      blood monocytes could be an extrarenal source of 1,25-(OH)2D3. Our results
      demonstrated that macrophages from normal individuals synthesize 1,25-(OH)2D3.
      The apparent Km for 25OHD3 was 6.6 +/- 0.5 nM and the maximum velocity was 47.4
      +/- 13.7 fmol 1,25-(OH)2D3/h.microgram DNA. The activity of this enzyme was
      reduced 37.2 +/- 3.1% by physiological concentrations (96 pmol/L) of 1,25-(OH)2D3
      in the incubation medium. Normal macrophages further hydroxylated 1,25-(OH)2D3 to
      more polar metabolites, and this catabolic activity was significantly enhanced by
      physiological concentrations of 1,25-(OH)2D3. In chronic renal failure,
      peripheral macrophages exhibited an enhanced 1 alpha-hydroxylase activity (8.2 +/
      0.8 vs. 4.2 +/- 0.5 fmol 1,25-(OH)2D3/microgram DNA.h in controls) and a
      decreased capacity to degrade 1,25-(OH)2D3. Exogenous 1,25-(OH)2D3, in
      physiological concentrations, reduced 1,25-(OH)2D3 synthesis to a degree (23.6 +/
      8.5%) comparable to that observed in normal cells. 1,25-(OH)2D3 production by
      macrophages did not correlate with the severity of hyperparathyroidism. Moreover,
      human PTH-(1-34) in supraphysiological concentrations (20,000 and 100,000 ng/L)
      did not stimulate the 1 alpha-hydroxylase activity of macrophages from either
      normal or uremic subjects. These results demonstrate that 1) normal peripheral
      macrophages metabolize 25OHD3 and 1,25-(OH)2D3; 2) macrophages in uremia display
      higher rates of 1,25-(OH)2D3 synthesis and lower rates of catabolism than normal
      macrophages; and 3) 1,25-(OH)2D3 deficiency, but not hyperparathyroidism, may
      play a role in the stimulation of 1,25-(OH)2D3 production by macrophages in
      chronic renal failure.

PMID- 1986016
TI  - Relationship of follicular fluid prorenin to oocyte maturation, steroid levels,
      and outcome of in vitro fertilization.
AB  - Prorenin (PR) is present in high concentrations in the follicular fluid (FF) of
      the preovulatory follicle. It is the predominant form of renin detected in FF.
      Its biosynthesis and secretion from the ovary are regulated by gonadotropins. In
      the present study we measured PR and steroid levels in FF from 136 follicles.
      Follicular fluids were obtained, 36 h after hCG injection, from 41 ovarian
      stimulated patients who underwent follicle puncture and oocyte retrieval for in
      vitro fertilization. We related FF PR to steroid levels and to the stage of
      oocyte-cumulus complex maturation. PR levels in 62 FF containing mature healthy
      fertilized oocytes averaged 2620 +/- 157 (+/- SE) ng/mL.h (728 +/- 44 ng/L.s;
      range, 1020-6880 ng/mL.h, 283-1911 ng/L.s). A subgroup of 16 of these follicles
      containing mature oocytes were from 7 women who conceived, in which PR levels
      spanned only the lower range from 1030-2720 ng/mL.h (286-756 ng/L.s). No patient
      conceived with FF PR above 2800 ng/mL.h (778 ng/L.s), yet one third of all mature
      follicles were above this range. Lower levels of PR were detected in FF
      containing immature oocytes (germinal vesicle stage) associated with either
      compact (1665 +/- 480 ng/mL.h; 463 +/- 133 ng/L.s; n = 22; P less than 0.02) or
      expanded (1785 +/- 193 ng/mL.h; 496 +/- 54 ng/L.s; n = 24; P less than 0.005)
      cumulus mass; a subgroup (n = 5) of follicles with immature oocytes and compact
      cumulus had very high levels of FF PR, ranging from 3830-7520 ng/mL.h (1064-2089
      ng/L.s), while the remainder had levels less than 1300 ng/mL.h (361 ng/L.s).
      Progesterone and estradiol (E2) were lower in FF surrounding immature oocytes
      associated with compact (P less than 0.005) or expanded (P less than 0.02)
      cumulus, than in those containing mature oocytes. Testosterone (T) and
      androstenedione were measured in only a fraction of the samples; there were no
      apparent differences between follicles containing mature and immature oocytes.
      However, T and androstenedione levels were high in the subgroup of follicles
      containing immature oocytes and very high levels of PR. Of the hormones measured,
      T revealed the most striking relationship with PR (r = 0.62; n = 49; P less than
      0.001).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1986017
TI  - Coinheritance of two mild defects in low density lipoprotein receptor function
      produces severe hypercholesterolemia.
AB  - A family is described in which the probands, twin girls, had severe
      hypercholesterolemia suggestive of familial hypercholesterolemia (FH). The mother
      of the twins had normal plasma cholesterol levels, and the father had only
      moderate hypercholesterolemia. Moreover, low density lipoprotein (LDL) binding
      studies in cultured fibroblasts and isolated lymphocytes in the parents failed to
      reveal significantly reduced LDL receptor activity that is typical of FH
      heterozygotes. Turnover studies of LDL in the parents, however, revealed low
      fractional clearance rates (FCRs) for LDL. In cultured fibroblasts and isolated
      lymphocytes from the twin probands, binding of normal LDL was half normal or
      less. LDL turnover studies in the twins revealed a marked reduction in FCRs for
      LDL. When the twins were treated with lovastatin, however, FCRs for LDL increased
      significantly, suggesting enhancement of LDL receptor activity. This finding
      along with LDL binding studies in the cultured cells infer that the twins did not
      have homozygous FH. In addition, all family members tested negative for familial
      defective apolipoprotein-B-100, and LDL isolated from the mother and twins showed
      normal binding to normal fibroblasts. The overall data suggest that the severe
      hypercholesterolemia in the offspring was due to inheritance of mild to moderate
      defects of LDL receptor function from both parents. Although the latter defects
      could not be detected with certainty by in vitro tests in each parent, they were
      evident from LDL turnover tests. Coinheritance of these defects apparently
      produced severe hypercholesterolemia in the offspring.

PMID- 1986018
TI  - Abnormal sensitivity to glucose of human islets cultured in a high glucose
      medium: partial reversibility after an additional culture in a normal glucose
      medium.
AB  - In the experimental animal chronic hyperglycemia alters the islet's sensitivity
      to glucose. In the present study the glucose sensitivity of human pancreatic
      islets, isolated and purified, obtained from seven human pancreases using an
      automated method was evaluated. After a 12-h stabilization period, islets were
      cultured for 48 h in normal (5.5 mmol/L) or high glucose (16.7 mmol/L) medium.
      Islets were then perifused to study their insulin response to glucose. Islets
      cultured in the high glucose medium lost glucose-induced insulin release and,
      when challenged with an acute fall of glucose concentration in the perifusate,
      showed a paradoxical insulin release. Insulin release in response to 10 mmol/L L
      arginine was preserved in these islets, suggesting a selective reduction of the
      insulin response to glucose. An additional 48-h culture in 5.5 mmol/L glucose
      medium partially restored the sensitivity to glucose of the previously
      unresponsive islets. These findings indicate that short term exposure to high
      glucose concentrations induces a selective glucose insensitivity of human islets,
      which can be partially reversed by an additional culture in normal glucose
      medium.

PMID- 1986019
TI  - Thyroid ultrasonography helps to identify patients with diffuse lymphocytic
      thyroiditis who are prone to develop hypothyroidism.
AB  - The clinical usefulness of thyroid ultrasonography in the evaluation of patients
      with autoimmune thyroiditis has been investigated. Thyroid ultrasonography was
      performed in 1184 consecutive patients attending our clinic, and the echo density
      of the thyroid parenchyma was evaluated with respect to that of normal thyroid
      tissue. Diffuse thyroid hypoechogenicity was found in 44 of 238 (18.5%) patients
      with autoimmune thyroiditis; the degree of hypoechogenicity was significantly
      correlated with the levels of circulating thyroid autoantibodies. Thyroid
      function was normal in all 194 patients with normal thyroid echogenicity, whereas
      hypothyroidism was found in 28 of 44 (63.6%) with reduced thyroid echogenicity.
      Included in this group were 8 patients, euthyroid at the first observation, who
      developed hypothyroidism over an 18-month follow-up period. None of the 133
      patients with autoimmune thyroiditis and normal thyroid echogenicity followed for
      the same period of time became hypothyroid. Evidence of diffuse lymphocytic
      thyroiditis was obtained by histology after thyroidectomy (n = 10) or multiple
      fine needle aspiration cytology (n = 15) in 25 of the 44 patients with thyroid
      hypoechogenicity; on the other hand, focal thyroiditis was shown at histology in
      8 patients who had normal thyroid echogenicity. In conclusion, diffuse low
      thyroid echogenicity was found in about 20% of patients with autoimmune
      thyroiditis. This echographic pattern is indicative of diffuse autoimmune
      involvement of the gland and is associated with or may predict the development of
      hypothyroidism.

PMID- 1986020
TI  - A simple stress test for the evaluation of hypothalamic-pituitary-adrenal axis
      during the first 6 months of life.
AB  - In 33 normal infants, divided into 3 age groups (less than 1 month, 1-3 months,
      and 3-6 months) plasma cortisol was measured at 2230, 2300, and 2330 h. Baseline
      plasma cortisol at 2230 h. was, as expected, low in all infants, with mean +/-
      SEM values of 41 +/- 5, 72 +/- 14, and 97 +/- 17 nmol/L in each group,
      respectively. Thirty and 60 min after the painful stimulus of the venipuncture,
      plasma cortisol increased significantly (P less than 0.0005), reaching a maximum
      increase up to 458 +/- 50, 392 +/- 66, and 455 +/- 97 nmol/L in each age group,
      respectively. We conclude that in these infants the hypothalamic-pituitary
      adrenal axis was functionally intact and responded to the painful stimulus of the
      venipuncture by a significant increase in plasma cortisol. This test may be used
      as a simple procedure for the evaluation of the integrity of the hypothalamic
      pituitary-adrenal axis without the administration of pharmacological agents. Its
      usefulness, however, should be validated with patients having a disorder of the
      system.

PMID- 1986021
TI  - Falsely elevated serum parathyroid hormone levels due to immunoglobulin G in a
      patient with idiopathic hypoparathyroidism.
AB  - A 73-yr-old patient with idiopathic hypoparathyroidism was admitted to our
      hospital in May 1981. The immunoreactive PTH (iPTH) level determined by RIA using
      antiserum specific for the C-terminal region of PTH-(65-69) was in the upper
      normal range (0.6 ng/mL) and over the next 7 yr increased gradually to 6 ng/mL.
      Since iPTH levels determined using other commercial RIA kits remained constantly
      decreased or in the undetectable range, we studied the mechanism of false
      elevation of iPTH in this patient. The patient's serum contained no binding
      protein to the tracer ([125I]) [Tyr45] human PTH-(46-84)), nor was any
      heterophilic antibody to the first [guinea pig immunoglobulin G (IgG)] or the
      second antibody (goat IgG) detected. Consistent with these findings, the dilution
      curve of the serum was parallel with that of standard bovine PTH-(1-84). Gel
      filtration analysis revealed that the iPTH-like substance was eluted in the void
      volume (apparent mol wt, greater than 70,000). Almost all of the iPTH-like
      substance was adsorbod by a protein-A-Sepharose column. When the IgG fraction
      purified by protein-A-Sepharose affinity chromatography was applied to an
      antihuman IgG lambda-Sepharose column, 72% of the iPTH-like substance was
      detected in the IgG lambda. These results suggest that the falsely elevated iPTH
      in the patient's serum was due to IgGs (mainly IgG lambda), which were cross
      reactive with the antiserum highly specific for the C-terminal region of human
      PTH-(65-69).

PMID- 1986022
TI  - Effect of a single infusion of aminohydroxypropylidene on calcium and bone
      metabolism in healthy volunteers monitored during 2 months.
AB  - Recently, bisphosphonates have been used to prevent postmenopausal bone loss. As
      the effects of bisphosphonates on normal bone metabolism are unknown, 3-amino-1
      hydroxypropylidene-1,1-diphosphonate (APD) was studied in healthy subjects. The
      effects of a single 20-mg APD infusion on biochemical parameters of calcium and
      bone metabolism were investigated during 2 months in 10 healthy male volunteers.
      This single moderate dose of APD reduced biochemical parameters of bone
      resorption during the time of follow-up. After 2 months, urinary hydroxyproline
      excretion was still below the basal level. The decreased serum calcium levels did
      not return to basal values. Biochemical parameters of bone formation, serum
      alkaline phosphatase and osteocalcin, showed a slight increase during the first
      month after stimulation of the parathyroids and a corresponding increase in serum
      1,25-dihydroxyvitamin D. These formation parameters decreased thereafter,
      probably representing coupling between bone resorption and bone formation.

PMID- 1986024
TI  - Twenty-four-hour profile of plasma growth hormone-binding protein.
AB  - In experimental animals each burst of GH pulse is followed by a wave of receptor
      turnover and an increase in serum GH-binding protein (GH-BP), which occurs 60 min
      after the GH peak. The present report describes the 24-h profile of plasma GH-BP
      and its correlation to GH pulsatility in normal individuals. Four normally
      growing children in early puberty were the subjects of this study. Blood was
      withdrawn continuously for 24 h in 30-min fractions. Pulse analysis of both GH
      and GH-BP was performed by the Pulsar program. The vast majority of the GH pulses
      were accompanied by GH-BP pulses within 30 min. Correlation of plasma GH levels
      to GH-BP levels on the residual series above the smoothed baseline of all 172
      individual samples was r = 0.447 (P less than 0.001). Thus, plasma GH-BP levels
      fluctuate rapidly in relation to the pulsatility of plasma GH levels. This may
      influence the GH disappearance rate and brings into question some of the
      deconvolution calculations of GH secretory impulses.

PMID- 1986023
TI  - Osteomalacia in hereditary hypophosphatemic rickets with hypercalciuria: a
      correlative clinical-histomorphometric study.
AB  - We characterized the bone disease of transilial biopsy specimens from children
      with hereditary hypophosphatemic rickets with hypercalciuria (HHRH) and
      genetically related asymptomatic hypercalciuric subjects. All HHRH patients
      showed irregular mineralization fronts, markedly elevated osteoid surface and
      seam width, increased number of osteoid lamellae, and prolonged mineralization
      lag time. These findings are consistent with a mineralization defect and indicate
      unambiguously that the bone disease in HHRH is osteomalacia. The only abnormality
      seen in the asymptomatic hypercalciuric subjects was slightly extended osteoid
      surface. Parametric and nonparametric statistical analyses performed on a pooled
      sample of HHRH patients and asymptomatic hypercalciuric subjects revealed a very
      high inverse correlation and a tight linear relationship between serum phosphorus
      and osteoid parameters. Serum 1,25-dihydroxyvitamin D, which is low in other
      forms of hereditary hypophosphatemia and osteomalacia, is elevated in HHRH and
      correlated positively with osteoid parameters and the mineralization lag time.
      Serum alkaline phosphatase showed similar relationships. These results as well as
      the clinical, biochemical, and radiological remission of bone disease consequent
      to phosphate therapy strongly suggest that in HHRH 1) hypophosphatemia alone is
      sufficient to cause osteomalacia; and 2) the elevation of 1,25-dihydroxyvitamin D
      reflects the degree of the primary renal phosphate leak, but is not involved in
      the pathogenesis of the bone disease.

PMID- 1986025
TI  - Clinical review 17: Immunotherapy of type I diabetes mellitus.

PMID- 1986026
TI  - Daily cortisol production rate in man determined by stable isotope dilution/mass
      spectrometry.
AB  - Growth retardation as well as the development of Cushingoid features in adrenally
      insufficient patients treated with the currently accepted replacement dose of
      cortisol (33-41 mumol/day.m2; 12-15 mg/m2.day) prompted us to reevaluate the
      cortisol production rate (FPR) in normal subjects and patients with Cushing's
      syndrome, using a recently developed thermospray liquid chromatography-mass
      spectrometry method. The stable isotope [9,12,12-2H3]cortisol was infused
      continuously for 31 h at about 5% of the anticipated FPR. Blood samples were
      obtained at 20-min intervals for 24 h, spun, and pooled in 4-h groups. Tracer
      dilution in plasma was determined by liquid chromatography/mass spectrometry. The
      method was validated with controlled infusions in 6 patients with adrenal
      insufficiency. Results from 12 normal volunteers revealed a FPR of 27.3 +/- 7.5
      mumol/day (9.9 +/- 2.7 mg/day) or 15.7 mumol/day.m2; 5.7 mg/m2. day). A
      previously unreported circadian variation in FPR was observed. Patients with
      Cushing's syndrome demonstrated unequivocal elevation of FPR and cortisol
      concentration correlated during each sample period in normal volunteers,
      indicating that cortisol secretion, rather than metabolism, is mainly responsible
      for changes in plasma cortisol. Our data suggest that the FPR in normal subjects
      may be lower than previously believed.

PMID- 1986027
TI  - Dual defects in pulsatile growth hormone secretion and clearance subserve the
      hyposomatotropism of obesity in man.
AB  - We have examined the mechanisms underlying reduced circulating GH concentrations
      in the obese human. Computer-assisted (deconvolution) analysis was used to
      determine endogenous GH secretory and clearance rates quantitatively from entire
      24-h plasma GH concentration profiles. These analyses revealed that the half-life
      (t 1/2) of endogenous GH was significantly shorter in obese (11.7 +/- 1.6 min)
      than in normal weight subjects (15.5 +/- 0.81 min; P less than 0.01). The
      accelerated blood disposal rate of GH was not due to decreased circulating
      concentrations of GH-binding protein, since the latter were similar in obese (25
      +/- 1.0%) and normal weight (24 +/- 2.3%) men. However, obese men had
      significantly fewer GH secretory bursts (3.2 +/- 0.53 vs. 9.7 +/- 0.67/day; P
      less than 0.01). Among the rare GH secretory bursts that occurred in obese
      subjects, there were significantly prolonged mean intersecretory burst intervals
      (282 +/- 65 vs. 131 +/- 11 min; P less than 0.05). The resultant daily GH
      production rate in obese men was reduced to one fourth that in normal weight
      individuals. Both GH secretion rate and burst frequency were negatively
      correlated with the degree of obesity (ponderal index). The decreases in GH burst
      frequency and half-life were specific, since GH secretory pulse amplitude
      (maximal rate of GH release), the mass of GH released per burst, and the duration
      of computer-resolved GH secretory bursts were not different in obese and normal
      weight men. We conclude that obese men harbor a double defect in GH dynamics
      involving both GH secretion and clearance, and that the severity of the GH
      secretory deficiency is proportionate to the degree of obesity.

PMID- 1986028
TI  - Physiological free fatty acid concentrations do not increase free estradiol in
      plasma.
AB  - Consumption of dietary fat has been linked to the high incidence of breast
      cancer. The in vitro effects of palmitate, oleate, linoleate, and
      eicosapentaenoate at supraphysiological concentrations [1.8-4.8 mM; endogenous
      (0.8) plus added (1-4)] on the binding of 17 beta-estradiol (E2) to sex hormone
      binding globulin and albumin were evaluated in plasma, using centrifugal
      ultrafiltration. The E2-sex hormone-binding globulin complex was significantly
      dissociated by oleate, linoleate, eicosapentaenoate, and palmitate at 1.8 to 2.8
      mM concentrations. The same FFA caused a significant increase in E2 binding to
      albumin at similar concentrations. However, only the unsaturated fatty acids at
      3.8 to 4.8-mM concentrations (i.e. oleate, linoleate, and eicosapentaenoate)
      significantly increased the nonprotein-bound free E2 fraction. Thus, these
      results suggest that free E2 concentrations are not affected by physiological
      concentrations of FFA.

PMID- 1986029
TI  - Circadian variation in ionized calcium and intact parathyroid hormone: evidence
      for sex differences in calcium homeostasis.
AB  - The rate of bone loss with age and the incidence of osteoporosis are greater in
      women than men, which led us to question whether subtle sex differences may occur
      in the circadian variation of serum ionized calcium (iCa) and PTH. We measured
      iCa hourly and intact PTH every 2 h for 26 h in 25 women (21-69 yr) and 24 men
      (20-67 yr) consuming self-selected diets. Urine was collected at 0800-1600, 1600
      2400, and 2400-0800 h. Serum iCa levels followed a circadian rhythm in both sexes
      (P less than or equal to 0.01), and the patterns differed between sexes, notably
      during early morning, when serum iCa levels were lower in women (P = 0.02).
      Urinary calcium excretion and fractional excretion of calcium declined in both
      sexes at night (2400-0800 h), but the decline in men was significantly greater (P
      = 0.02). Similarly, the percent reduction in urinary calcium excretion at night
      was greater in men than in women (34% vs. 17%; P less than or equal to 0.05). In
      women, 26-h mean serum iCa values correlated significantly with total daily
      calcium intake (r = 0.44; P = 0.03). Serum intact PTH levels showed a significant
      circadian pattern in both sexes (P less than or equal to 0.001). The patterns of
      serum intact PTH differed between the sexes (P = 0.05), with an earlier and
      greater increase at night in men. This blunted nocturnal rise in PTH in women may
      explain the poor nocturnal adaptation to fasting found in women who, despite
      lower calcium intake, did not reduce urinary calcium loss at night as effectively
      as men.

PMID- 1986030
TI  - Pulsatile thyrotropin release and thyroid function in acromegalics before and
      during subcutaneous octreotide infusion.
AB  - The pulsatile secretion of TSH was studied in eight patients with active
      acromegaly before treatment and after 1 month of therapy consisting of the sc
      infusion of 300 micrograms octreotide/day. Mean GH levels decreased from 37.1 +/-
      7.2 to 5.2 +/- 1.4 mU/L (P = 0.002). Insulin-like growth factor-I levels
      decreased from 82.9 +/- 8.8 to 37.8 +/- 9.8 nmol/L (P less than 0.01) and
      normalized in five of the eight patients. In one patient TSH levels were
      undetectable before and during octreotide therapy. In the other seven patients,
      Cluster analysis revealed 11.9 +/- 0.8 pulses/24 h, with a mean pulse width of 81
      +/- 4.6 min, a mean pulse height of 1.33 +/- 0.42 mU/L, and a mean pulse
      increment of 0.36 +/- 0.12 mU/L. During octreotide therapy these pulse parameters
      remained unchanged. Pulse height and amplitude increased significantly during the
      night (i.e. from 2000-0800 h) in both untreated and treated patients. The
      acrophase was unchanged by therapy. During therapy T3 levels decreased from 2.05
      +/- 0.17 nmol/L to 1.44 +/- 0.08 nmol/L (P = 0.001), while rT3 levels increased
      from 0.14 +/- 0.02 nmol/L to 0.19 +/- 0.03 nmol/L (P less than 0.05). Plasma T4
      levels remained unchanged. From these studies we conclude that the TSH pulse
      generator is unchanged in active acromegaly and apparently unaffected by chronic
      octreotide infusions.

PMID- 1986031
TI  - Dose-dependent effects of scopolamine on nocturnal growth hormone secretion in
      normal adult men: relation to delta-sleep changes.
AB  - To explore the sensitivity of nocturnal GH secretion to different degrees of
      cholinergic blockade, we investigated the effects of two doses of the muscarinic
      receptor antagonist scopolamine (SCOP; 3.0 and 6.0 micrograms/kg, im) and
      placebo, administered in a randomized fashion at 2300 h on three nights to eight
      normal male volunteers. Both doses of SCOP produced significant reductions in
      mean nocturnal GH concentration compared to the effects of the placebo; the
      higher dose of SCOP reduced GH to a greater degree than the lower dose, but this
      difference was not statistically significant (mean, 2.3 micrograms/L after 6
      micrograms/kg vs. 3.0 micrograms/L after 3 micrograms/kg). Both SCOP doses
      significantly shifted GH secretion into later portions of the night, with a
      significantly greater delay observed after the larger dose. Similarly, a
      significant delay in the time of the GH rise was produced by SCOP. In contrast,
      the effects of both doses of SCOP on delta-sleep or sleep onset were small. These
      data confirm earlier reports demonstrating that cholinergic muscarinic input
      represents a potentially important source of regulation of nocturnal GH release
      and suggest that the magnitude of the reduction in GH and the extent of delay in
      the GH rise time may reflect quantitative differences in the degree of
      cholinergic blockade. These data are in agreement with recent studies suggesting
      that the timing of GH release need not be associated with delta-sleep per se.

PMID- 1986032
TI  - The role of free fatty acid metabolism in the pathogenesis of insulin resistance
      in obesity and noninsulin-dependent diabetes mellitus.
AB  - To investigate the mechanisms of insulin resistance in obesity and noninsulin
      dependent diabetes mellitus (NIDDM), we examined oxidative and nonoxidative
      pathways of free fatty acid (FFA) and glucose metabolism in 14 lean and 17 obese
      (with normal oral glucose tolerance) nondiabetic subjects and in 8 lean and 8
      obese subjects with NIDDM. FFA and glucose metabolism were measured using the
      sequential insulin clamp technique in combination with indirect calorimetry and
      infusion of [3-3H]glucose and [1-14C]palmitate. Obesity was characterized by
      enlarged fat mass, which correlated positively with the plasma FFA concentration
      (r = 0.62; P less than 0.01). FFA metabolism was less sensitive to insulin in
      obese than in lean nondiabetic subjects, but this defect could be overcome by
      increasing the plasma insulin concentration. NIDDM patients showed normal
      sensitivity to the inhibitory action of insulin on FFA metabolism; however,
      maximal suppression by insulin was impaired. The combination of obesity and NIDDM
      was associated with a further enhancement of reesterification of FFA than
      observed in either condition alone. In both obesity and NIDDM, the dose-response
      curve for suppression of hepatic glucose production by insulin was impaired.
      While obesity was primarily characterized by reduced sensitivity to the
      stimulatory action of insulin on oxidative and nonoxidative pathways of glucose
      metabolism, resistance to the effect of insulin on glucose metabolism in NIDDM
      was characterized by a reduced maximal response. The combination of obesity and
      NIDDM further impaired the sensitivity of liver glucose output and glucose
      oxidation to insulin. The hypothesis is advanced that in uncomplicated obesity,
      increased availability and oxidation of FFA leads, by the FFA/glucose cycle, to
      the impairment in glucose utilization. In NIDDM, on the other hand, the defect in
      glucose utilization is primary, and the enhanced rate of FFA oxidation may
      represent a compensatory phenomenon.

PMID- 1986033
TI  - Age-associated and cell-type specific changes in NGF requirement for neurite
      regeneration from trigeminal ganglion cells of the shrew (Suncus murinus).
AB  - Low density (20-50 cells/cm2), dissociated cultures of trigeminal ganglion (TRG)
      cells of the shrew, were made in a serum-free medium, and neurite growth was
      compared across ages of the animal and between NGF-free and NGF-rich conditions.
      TRG cells from newborn shrew (0-3 days old), which grew long neurites in an NGF
      rich medium, failed to grow any neurites in an NGF-free medium. In contrast, TRG
      cells from aged shrew (16-19 months), which grew neurites without NGF, exhibited
      no further increment in neurite length when NGF (50-200 ng/ml) was added to the
      culture medium. TRG cells from adult shrew (4-5 months) were revealed to be a
      mixture of NGF-dependent and NGF-independent cells. The NGF-dependent cells (20%
      of the population) had large-sized somata of 24-32 microns diameter (L-type
      cells) and 2-7 long neurites enriched with arborizations. The remaining NGF
      independent cells (80%) had small-sized somata (15-25 microns, S-type cells), and
      grew 1-3 neurites with a small number of arborizations. These findings suggest
      that the primary sensory neuron of the shrew has a cell-type specific critical
      period in the aging process with respect to the requirement of NGF for neurite
      promotion.

PMID- 1986035
TI  - Age-related changes of sympathetic outflow to muscles in humans.
AB  - Muscle sympathetic nerve activity (MSA) was recorded microneurographically from
      the tibial nerve in 40 healthy male subjects aged 18 to 75. Passive and graded
      head-up tiltings were loaded on the subjects. The effects of aging on the resting
      activity of muscle sympathetic nerve in supine position at rest (burst number per
      minute), increase in MSA from the resting level by orthostasis (slope of the
      regression line between sine of the tilt angle and MSA bursts per minute), and
      the MSA in upright standing position were analyzed. The resting MSA increased
      with age, and a significant positive correlation was observed between age and
      resting activity (Y = -6.83 +/- 0.876X, r = .882, p less than .001). The MSA was
      enhanced by head-up tilt linearly with the sine of the tilt angle, and a
      significant negative correlation was observed between age and the MSA increase by
      orthostasis (Y = 57.6 - 0.582X, r = . 843, p less than .001). Standing MSA
      increased significantly but less remarkably than resting MSA. It was concluded
      that aging increases the resting activity, but there is less increase in the
      standing activity of sympathetic outflow to muscles in humans.

PMID- 1986034
TI  - Thyroid function in a healthy elderly population: implications for clinical
      evaluation.
AB  - Evaluation of thyroid function in elderly people is complex and has generated
      some controversy about what is normal. This study analyzed thyroid function
      assays in an identified healthy elderly population of 216 subjects. Thyroxine,
      free thyroxine, triiodothyronine, T3 uptake, "supersensitive" thyrotropin, and
      thyroid antibody titers were performed. Histories of treatment for thyroid
      conditions were present in 13.9% (n = 30) of the population, and test results for
      an additional 4.3% (n = 8) revealed some hypothyroidism. These subjects were
      excluded from statistical analysis. Test results revealed significant differences
      from younger controls as well as skewed distributions for T4, FT4, and TSH. There
      were no significant correlations with increasing age or gender within the elderly
      population. 11.8% (n = 21) of the population exhibited elevated TSF levels with
      normal T4 values, and 23.0% (n = 41) exhibited a titer of one or both thyroid
      antibodies. Current reference ranges for thyroid tests are broad enough to
      include the range of values seen in the healthy elderly, but some cautions are
      discussed.

PMID- 1986036
TI  - An assessment of salivary function in healthy premenopausal and postmenopausal
      females.
AB  - The elderly represent the most rapidly growing segment of the U.S. population,
      and the majority of this group are females. The average woman can anticipate
      living about a third of her life beyond menopause, and many U.S. women undergo
      hormonal replacement in an attempt to relieve menopausal symptoms. Little is
      understood about the relationship between menopause, hormonal replacement
      therapy, and the oral structures, although oral discomfort, xerostomia, and
      salivary hypofunction have been associated with postmenopausal women. The effects
      of menopausal status and estrogen therapy on subjective reports of oral dryness
      and discomfort and objective measurements of major salivary gland output were
      assessed in 43 healthy premenopausal and postmenopausal females. No complaints of
      xerostomia or burning mouth and no alterations in the quantity of saliva occurred
      in this population. This study suggests that among healthy women salivary gland
      function is not significantly influenced by menopause or hormonal replacement
      therapy.

PMID- 1986037
TI  - Influence of thiamin supplementation on the health and general well-being of an
      elderly Irish population with marginal thiamin deficiency.
AB  - The effect of thiamin supplementation on the health and general well-being of 80
      randomly selected healthy elderly Irish women, from a population with marginal
      thiamin deficiency, was studied. Key variables affecting thiamin status were
      controlled. Weekly dietary intakes, subjective feelings, and activity assessments
      were measured during a 4-week baseline and 6-week double blind treatment period.
      Clinical assessments were performed during the last week of each period. For
      treatment, subjects were randomly assigned to either thiamin (10 mg daily) or
      placebo groups. Compared to baseline and placebo supplemented values, thiamin
      supplemented women experienced significantly increased appetite, energy intake,
      body weight and general well-being, and decreased fatigue. Thiamin
      supplementation also tended to reduce daytime sleep time, improve sleep patterns,
      and increase activity. These data suggest that evaluation of thiamin status is
      indicated when nonspecific conditions such as anorexia, weight loss, fatigue,
      depression, and sleep disorders are present in elderly persons.

PMID- 1986038
TI  - Abnormal arginine vasopressin response to cigarette smoking and metoclopramide
      (but not to insulin-induced hypoglycemia) in elderly subjects.
AB  - Aging is known to reduce arginine vasopressin (AVP) response to volumetric
      stimulations and to increase AVP responses to osmotic stimuli and to
      administration of metoclopramide (MCP). In order to gain a better insight into
      the effect of age on AVP secretion, we evaluated AVP responses to cigarette
      smoking, MCP, and insulin-induced hypoglycemia in 30 male subjects aged 22-81 and
      divided into 3 groups by age. Basal AVP concentrations were similar in all
      groups. The AVP response during the insulin tolerance test had a similar pattern
      and magnitude (2.5-fold increase) in all groups. AVP responses to MCP and
      cigarette smoking were similar in the two younger groups, with plasma AVP levels
      increased 2 times by MCP and 2.5 times by cigarette smoking. In contrast, both
      MCP- and cigarette smoking-induced AVP rises were significantly higher in the
      oldest group, where plasma AVP concentrations increased 2.5 times after MCP and
      3.25 times after smoking. When data of the MCP and cigarette smoking tests were
      combined, regression analyses showed a significant positive correlation between
      AVP peak responses to MCP and cigarette smoking in the oldest subjects. These
      data show that elderly humans have increased AVP responses not only to MCP but
      also to cigarette smoking, suggesting a common disorder for both alterations. In
      contrast, the lack of age-related changes in AVP response during the insulin
      tolerance test demonstrates that the mechanism underlying the AVP response to
      hypoglycemia is not affected by aging.

PMID- 1986039
TI  - A preliminary study comparing sleep restriction and relaxation treatments for
      insomnia in older adults.
AB  - This study compared Sleep Restriction Therapy (SRT) and Relaxation Therapy (RLT)
      as treatments for insomnia in a sample of community-residing elderly (mean age,
      69.7 years). SRT subjects (n = 10) and RLT subjects (n = 12) reported information
      about their sleep twice daily to a telephone recording machine for 2 weeks of
      baseline, 4 weeks of treatment, and 2 weeks at 3-month follow-up. Results showed
      sleep latency and waking after sleep onset were significantly reduced for both
      treatment groups under active treatment. Predictable reductions in time in bed
      and improved sleep efficiency reported during active treatment by SRT subjects
      were still apparent at 3-month follow-up; no corresponding changes were found for
      RLT. In both groups, increased total sleep time was reported at follow-up; the
      improvement for SRT subjects was approximately twice that seen in RLT. These
      findings, at this early stage in the development of behavioral treatments for
      insomnia in older adults, encourage further study.

PMID- 1986040
TI  - The relation of pain to depression among institutionalized aged.
AB  - Nursing home and congregate apartment residents (N = 598) were classified on the
      basis of a DSM-IIIR symptom checklist as suffering possible major, minor, or no
      depression; they also completed the Geriatric Depression Scale (GDS) and the
      Profile of Mood States (POMS). Possible major depressives reported more intense
      pain and a greater number of localized pain complaints than did minor
      depressives; nondepressed individuals reported the least intense pain and fewest
      localized complaints. The effect remained strong even when functional disability
      and health status were controlled statistically. Both pain intensity and number
      of localized complaints were correlated with GDS and POMS factor scores, but
      strength and direction of associations varied with level of depression. Item-by
      item examination of localized complaints again indicated that more depressed
      individuals were more likely to report pain, particularly where physicians had
      identified a physical problem that might account for the pain. Results are
      compared with previous research on pain among younger individuals. Implications
      for treatment of depressed elderly are discussed.

PMID- 1986041
TI  - Adult age differences in direct and indirect tests of memory.
AB  - Indirect tests of memory assess the influence of recent experience on task
      performance without requiring awareness of remembering. Evidence concerning
      whether there are reliable age differences on such indicators of implicit memory
      has been inconsistent. This inconsistency may be related either to the low power
      of previous studies, or the contamination of indirect measures by conscious
      memory retrieval strategies. In a statistically powerful test of this question,
      indirect and direct tests of memory were administered to 584 adults from three
      age groups (19-36 years, 55-69 years, 70-86 years). Significant age differences
      in favor of the young were found on the indirect test as well as direct tests,
      suggesting that there are small but reliable age differences in implicit memory.
      Correlational analyses examining the relationship of memory performance to other
      cognitive variables indicated that the indirect test was supported by different
      components than the direct tests.

PMID- 1986042
TI  - The relative influence of intelligence and age on everyday memory.
AB  - A short memory test that provides analogs of everyday activities was used to
      investigate the relationship between everyday memory, cognitive abilities,
      participation in social, domestic, and leisure pursuits, and health status among
      94 community-dwelling people aged between 70 and 93 years. Multiple regression
      analysis revealed that while fluid intelligence was a significant predictor of
      performance on most of the memory items, age was also a significant predictor of
      performance on prospective and verbal memory items, over and above the effects of
      intelligence. Crystallized intelligence and years of formal education showed
      little predictive power, but an index of participation in social and domestic
      activities was a good predictor of verbal, visual, and spatial memory items. It
      is concluded that cognitive decline in aging involves more than a simple decline
      in fluid intelligence.

PMID- 1986043
TI  - Discrimination of short duration tones by elderly subjects.
AB  - The ability to discriminate the frequency of short duration tone pulses was
      investigated with 28 elderly subjects. In a previous study, Cranford, Stream,
      Rye, and Slade (1982) found that subjects with unilateral temporal lobe lesions
      were impaired in their ability to discriminate small changes in the frequency of
      such signals at ears located opposite the lesions. In the present study, although
      considerable intersubject variability was observed, several subjects exhibited
      deficits on the brief tone frequency difference limen test similar to that
      observed with temporal lobe lesion patients, but present at both ears. The
      occurrence of a discrimination problem was significantly correlated with subject
      age, but not with audiometric hearing level, thus suggesting the sensitivity of
      the test to the central neural effects of aging.

PMID- 1986044
TI  - How stressful is retirement? Findings from the Normative Aging Study.
AB  - The stressfulness of retirement both as a transitional event experienced during
      the past year and as a life stage was investigated. Transitional stress was
      assessed using a life events approach, and stage stress using a "hassles"
      approach. Respondents were 1,516 male participants in the Normative Aging Study,
      45% of whom were retired. Among those retiring in the past year, respondents' own
      and spouse's retirement were rated the least stressful from a list of 31 possible
      events. Only 30% found retirement stressful. Retirement hassles were also less
      frequently reported and were rated less stressful than the work hassles of men
      still in the labor force. The only consistent predictors of both transitional and
      stage retirement stress were poor health and family finances; personality did not
      predict retirement stress.

PMID- 1986045
TI  - Living arrangements and sources of caregiving.
AB  - This study examined both the prevalence of different types of caregivers (in
      terms of the relation to the individual), and whether living with someone is more
      important for caregiving than the relation of an elder to an individual.
      Caregiving is examined in terms of IADL and emotional support. Analyses are
      conducted using three separate random samples of those who are married and living
      with a spouse, those who live alone, and those who live with nonspousal others in
      Winnipeg, Manitoba, Canada. The results confirm previous research pointing out
      that married people tend to receive assistance from their spouse. Among
      nonmarrieds, children are named most frequently as the primary caregiver. After
      children, however, those who live alone tend to receive assistance from friends,
      and those who live with nonspousal others receive assistance from siblings. The
      data further document the importance of the structural characteristic of living
      with someone, rather than marital status, for assistance with IADL.

PMID- 1986046
TI  - Social networks, health, and emotional well-being among the oldest old in London.
AB  - A survey of the health and social circumstances of 662 people aged 85 and over,
      living at home in inner London, was conducted in 1987. A primary aim was to
      analyze the structure of social support networks of the sample in relation to
      respondents' emotional well-being and met and unmet needs for practical help. The
      conceptual and methodological framework that was applied to the study was derived
      from the theory of social networks. In confirmation of the common assumption that
      people aged 85+ are different from younger elderly people, as they are the
      "survivors," high levels of social support and informal help were given to most
      respondents. Although associations were found between social network variables
      and the provision of informal help, multifactorial analysis showed that health
      status explained more of the variation in emotional well-being.

PMID- 1986047
TI  - Regional retirement migration: the case of Cape Cod.
AB  - Using microlevel data from the Cape Cod Retirement Migration Study, this study
      addressed two questions: Why are regional destinations attractive to older
      migrants? Are there any salient differences among regional retirement migrants?
      Cape Cod, Massachusetts, attracts regional migrants for primarily three reasons:
      it is a familiar place to most migrants; it is a proximate setting for a variety
      of amenities; and it is relatively near these migrants' communities of origin,
      allowing them to maintain ties to previous residences. We argue that a regional
      move allows migrants to preserve some degree of continuity in their lives that
      would be impossible had they moved across greater distances, and that the
      experiences of intrastate migrants illustrate this theme of continuity to a
      greater extent than those of interstate regional migrants. Our research provides
      strong evidence that the distance of the move is an important dimension of the
      migration process for older people and one that can be fruitfully studied on both
      the macro and micro levels of analysis.

PMID- 1986048
TI  - Adolescent and elderly white male suicide trends: evidence of changing well
      being?
AB  - This study investigated the relationship proposed by Preston (1984) between
      suicide trends and the changing status of America's dependent populations. Since
      World War II, as adolescent suicide rates have risen and elderly suicide rates
      declined, the rates have generally converged. In particular, adolescent and
      elderly suicide rates among White males reveal some of the most dramatic shifts
      relative to other age-race-sex-specific groups. This social-demographic study
      examined indicators of well-being as proposed by Preston (1984) to determine
      whether these structural factors can account for White male adolescent and
      elderly suicide trends. Using annual U.S. suicide rates for the White male
      populations aged 15 to 24 and 65 and over, I examined the hypotheses that (a) the
      rising suicide trend among the adolescent population is associated with a
      deteriorating state of well-being for adolescents, and (b) the generally
      declining suicide trend among the elderly population is associated with an
      improving state of well-being for elderly persons. A post-World War II annual
      time series analysis was used in this research for the period 1946 to 1986. The
      findings suggest that family dissolution and White children living in poverty are
      associated with White male adolescent suicide trends and that societal affluence
      is associated with White male elderly suicide trends. The implications of these
      findings for future adolescent and elderly suicide trends are also addressed.

PMID- 1986049
TI  - The impact of elder health, caregiver involvement, and global stress on two
      dimensions of caregiver burden.
AB  - This study examined the simultaneous effects of an elder's health, caregiver
      involvement, and stress on caregiver burden, addressing the questions: (a) What
      are the direct and indirect effects of level of elder's impairment, caregiver
      involvement, and stress on personal and interpersonal burden? (b) How do these
      relationships differ between spouse and adult-child caregivers? Data were from
      the 1982 National Long Term Care Survey. Results using linear structural
      relations analysis showed the effect of a frail elder's health and functioning on
      personal and interpersonal burden is mediated by task involvement and perceived
      global stress. Contrary to expectation, there were few differences in the direct
      effect of each dimension of health, functional limitations, cognitive status, and
      global health rating on each dimension of burden. Although the results suggested
      mean differences between spouse and adult child caregivers on key variables,
      there were no differences by family relationship in the system of relationships
      that comprise the process linking health and burden.

PMID- 1986051
TI  - Timing in the movement of jaws, tongue, and hyoid during feeding in the hyrax,
      Procavia syriacus.
AB  - The anatomical structures used during mammalian feeding are morphologically
      linked by their connecting musculature, suggesting a predictable timing
      relationship among their movements. Cine-x-ray (100 frames per second) was used
      to record feeding behavior in four adult hyraxes (Procavia syriacus), herbivores.
      Movement of jaws, tongue, and hyoid bone was cyclic, and prior to the first
      swallow cycle, cycle duration was constant through time for all structures.
      Minimum gape, beginning of forward movement of the tongue and hyoid, and
      beginning of intrinsic tongue expansion occurred simultaneously over a large
      number of cycles. However, maximum gape, maximum protrusion of hyoid, and maximum
      forward position of the tongue happened at statistically different points in
      time. After the first swallow, cycle duration increased. Most of the variation in
      cycle duration can be explained by variation in the opening or forward phase of
      movement; the closing and return phases are constant in duration. These results
      are a quantitative description of the coordination that exists during different
      feeding behaviors (ingestion, intraoral transport, mastication, and swallowing)
      in normal, freely functioning hyraxes. The patterns of phase duration differ from
      some results obtained by using anesthetized animals.

PMID- 1986050
TI  - Involvement of protein kinase C in the regulation of oocyte maturation in
      amphibians (Rana dybowskii).
AB  - Ovarian oocytes of Rana dybowskii, isolated early in the hibernation period (late
      autumn), failed to mature, i.e., germinal vesicle breakdown (GVBD), in response
      to progesterone during in vitro follicle culture. Oocytes collected during the
      middle hibernation period matured in response to progesterone, whereas those
      collected late during the hibernation period (close to the breeding season)
      underwent spontaneous maturation without added hormone (Kwon et al., '89). The
      maturational response (GVBD) of oocytes, collected at the three stages of
      hibernation, to protein kinase C (PKC) activation was investigated and compared
      to that of progesterone stimulation. A phorbol ester, phorbol 12-myristate 13
      acetate (TPA) was used for PKC activation. TPA addition to cultured follicles
      collected during the early or middle period of hibernation induced oocyte GVBD.
      The incidence of maturation (% GVBD) induced by TPA varied markedly between
      animals. TPA (10 microM) induced oocyte maturation in the presence or absence of
      follicle cells. The time course of the TPA-induced maturation was similar to that
      of progesterone-stimulated maturation (ED50, 7-9 h). TPA also accelerated the
      onset of maturation of the follicular oocytes exhibiting spontaneous in vitro
      maturation. Both TPA- and progesterone-stimulated maturation was blocked by
      treatment with cycloheximide (1 microgram/2 ml), forskolin (9 microM) (an
      adenylate cyclase stimulator), and verapamil (0.27 mM) (a calcium transport
      blocker). Treatment of oocytes with a calmodulin antagonist N-(6-aminohexyl)-5
      chloro-1-naphthalenesulfonamide (W-7) (100 microM) or a PKC inactivator 1-(5
      isoquinolinylsulfonyl)-2-methyl-piperazine (H-7) (50 microM) likewise suppressed
      TPA- or progesterone-induced maturation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1986052
TI  - Relative developmental abilities of hamster 2- and 8-cell embryos cultured in
      hamster embryo culture medium-1 and -2.
AB  - The relative developmental abilities of hamster 2- and 8-cell embryos in culture
      were compared using two versions of hamster embryo culture medium (HECM). These
      media differed primarily in the number of amino acids present, i.e., 20 amino
      acids in HECM-1 and four amino acids in HECM-2. When 2-cell embryos were cultured
      for 24 h, the percentages of greater than or equal to 4-cell embryos obtained in
      both HECM-1 and HECM-2 were comparable (congruent to 93%); at the end of 48 h,
      the proportion of greater than or equal to 8-cell embryos obtained in HECM-1
      (82.5%) was significantly (P less than or equal to 0.001) more than that obtained
      in HECM-2 (67.9%). Interchange of media, after 24 h culture, did not enhance the
      ability of cultured 2-cell embryos to become blastocysts. When 8-cell embryos
      were cultured for 18 h in HECM-1 and -2, there was no appreciable difference in
      the proportion of total blastocysts formed (89-91%). However, there were
      significantly (P less than or equal to 0.001) more late blastocysts in HECM-2
      than in HECM-1 (68.2% vs. 38.4%). Embryo development from 2- and 8-cell stages
      was compared in media that differed by the presence and absence of phenol red and
      penicillin-G. There was no difference in embryo development when these compounds
      were present or absent. Similarly, the difference in pyruvate concentration
      between HECM-1 and -2 (0.5 and 0.2 mM, respectively) did not affect embryo
      development.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1986053
TI  - Lower extremity arterial disease in elderly subjects with systolic hypertension.
AB  - The ratio of ankle-to-arm systolic blood pressure (ankle/arm index or AAI)
      appears to be a non-invasive indicator of flow-significant atherosclerosis and
      may be a useful measure of burden of disease in a high risk population. The
      prevalence of lower extremity arterial disease (LEAD) was assessed by this method
      in the Systolic Hypertension in the Elderly Program (SHEP). Subjects were aged 60
      and older with systolic blood pressure greater than 160 mmHg upon entry to the
      study. An AAI of 0.90 or less was considered indicative of flow-significant LEAD.
      The prevalence of LEAD by this method was 26.7% (50/187), while the prevalence of
      intermittent claudication (IC) was only 6.4% (12/187). Of those with IC, 66.7%
      (8/12) had confirmed LEAD. The prevalence of LEAD as measured by AAI increased
      with age in women and was associated with a history of current smoking and lower
      levels of high density lipoproteins. In this study population with systolic
      hypertension, LEAD, as measured by the AAI, is more prevalent than previously
      described in elderly populations and is associated with other risk factors for
      atherosclerosis.

PMID- 1986054
TI  - Stroke rehabilitation: Australian patient profile and functional outcome.
AB  - A prospective, multi-institutional, population based study identified 1274 non
      surgical stroke admissions to all hospitals in a major Australian city during
      1984. The demographic and diagnostic profile and the nature of functional
      recovery of all 258 first stroke survivors who were referred for inpatient
      rehabilitation are presented. The median duration of rehabilitation stay was 49
      days. The mean functional independence score, as measured on a modified Barthel
      Index at admission was 44, compared with 78 on discharge, a mean improvement of
      34. Stair climbing had the lowest mean value on admission (12), while bowel
      control had the lowest residual deficit on discharge (95). The stroke study group
      was representative of the unimpaired aged population in all respects except
      ethnicity, where differences are attributed to age. The variables identified as
      significant are; side and severity of paralysis, age and sex, marital status and
      ethnicity. Stroke rehabilitation outcome was not influenced by etiology, site of
      lesion, arterial distribution, occupation or education.

PMID- 1986055
TI  - Trends in female breast cancer in Connecticut and the United States.
AB  - Trends for female breast cancer were examined by age, period and cohort for the
      years 1950-1984 in U.S. mortality. Connecticut mortality and Connecticut
      incidence. Birth cohort patterns were evident for all three sets of data. The
      results confirm a continuing increase in invasive breast cancer by providing
      evidence of a strong birth cohort pattern, over a time series of 90 years of
      birth cohorts. This trend appears to be real for the most part because of the
      cohort patterns and because there is minimal underdetection in data obtained by
      autopsy and blind biopsy. Secondly, when cohort modeling is applied to breast
      cancer mortality, there is an indication of a modest decline in recent breast
      cancer mortality (in the face of an apparent long-term increase), which suggests
      that control of breast cancer mortality may have developed in recent decades,
      perhaps through earlier detection and improved treatment. Finally, in contrast
      with a prior report, there is little evidence for a clinically important
      difference in time trend between pre- and postmenopausal breast cancer.

PMID- 1986056
TI  - Leisure-time physical activity as an estimate of physical fitness: a validation
      study.
AB  - This paper describes a new interview questionnaire for the assessment of leisure
      time physical activity (LTPA), and its validation as an alternative estimate of
      physical fitness. British subjects (77 males, 41 females) provided details of
      their LTPA over a period of a "typical" 2 weeks, enabling the estimation of the
      energy expended. Physical fitness was assessed with a battery of measures, the
      optimal single measure being sub-maximal physical work capacity (PWC). The
      questionnaire showed LTPA to be stable following test-retest administration (r =
      0.86; p less than 0.0001) for total LTPA energy expenditure. Total LTPA was found
      to be significantly related to PWC (r = 0.48, p less than 0.0001), as were very
      hard (r = 0.55; p less than 0.0001) and hard LTPA (r = 0.38; p less than 0.0001).
      Multiple regression analysis with PWC as the dependent variable yielded a
      multiple correlation of r = 0.87, with significant contributions from very hard
      and hard LTPA. It is concluded that whilst this questionnaire is both reliable
      and a valid estimate of physical fitness amongst a population consistent in their
      leisure-time physical activities, there is scope for its further use within
      larger populations, allowing for an analysis of the effects of age and gender on
      the associations so far observed.

PMID- 1986057
TI  - Sleep patterns in rural elders: demographic, health, and psychobehavioral
      correlates.
AB  - Altered sleep patterns, including changes in bedtime, sleep latency, total sleep
      time, and arising time, have been reported to occur with increasing age. We
      examine self-reported sleep patterns in a geographically-defined population (n =
      3097) of persons aged 65 years and older. Sleep patterns were characterized
      according to demographic variables, clinical conditions, and physical,
      psychological, and social functioning. Sleep latency and total hours of sleep
      increased with age, and older respondents went to bed earlier. The percentage of
      respondents who reported feeling rested in the morning decreased with age. Women
      went to bed later, had longer sleep latency, and fewer hours of sleep than men,
      and were less likely to report feeling rested than men. Sleep patterns were also
      related to educational attainment, self-perceived health status, physical
      functional status, psychotropic drug use, alcohol use, depressive symptoms, life
      satisfaction, and social and recreational activity level. This population study
      suggests that sleep problems among the elderly are sometimes associated with
      treatable health conditions and modifiable behavioral and environmental
      characteristics.

PMID- 1986059
TI  - Recent life change and large bowel cancer. Data from the Melbourne Colorectal
      Cancer Study.
AB  - In a large, population based, epidemiological study of colorectal cancer, The
      Melbourne Colorectal Cancer Study, several etiological factors were investigated.
      Persons' recent life changes, as well as the degree of upset they experienced as
      a result of these changes, were included. Interviews with 715 histologically
      confirmed new cases of colorectal cancer occurring over a 12-month period in
      Melbourne, Australia, and with 727 age and sex matched community controls were
      conducted. As one of the methods of assessing any effect of recall bias, 179
      hospital controls were also investigated. Major illness or death of a family
      member, major family problems and major work problems were found to be
      significantly more common for cases over the 5 years preceding diagnosis compared
      to controls. Cases also reported being significantly more upset with their recent
      life changes than did controls. No significant differences in results were found
      between males and females, or between colon cancer and rectal cancer patients.
      Although the possibility of recall bias, was not completely controlled for in
      this study, it was probably not an important factor in explaining case-control
      differences. Recent life changes, and their perceptions, may have significance in
      the development of large bowel cancer.

PMID- 1986058
TI  - Progression of renal insufficiency in analgesic nephropathy: impact of continuous
      drug abuse.
AB  - Twenty-three patients with analgesic nephropathy and apparent cessation of drug
      abuse were tested for blood acetaminophen and salicylate on the occasion of
      routine renal control examinations. In 12 patients (mean creatinine level 2.74 +/
      1.09 mg/dl) no deterioration of renal function was noted within a 1-year
      observation period (Group 1). In 11 patients a significant progression of renal
      insufficiency was observed (mean creatinine level rose from 3.86 +/- 1.06 to 6.40
      +/- 3.18 mg/dl within the same observation period; Group 2). Blood tests for
      acetaminophen and salicylate were positive in 2 patients of Group 1 and in 9
      patients of Group 2 (chi 2 = 7.326), p less than 0.01). Our data emphasize the
      importance of a continuous analgesic abuse hidden from the medical staff with
      regard to the progression of renal insufficiency in analgesic nephropathy.

PMID- 1986060
TI  - Clustering of cancer in families of patients with primary lung cancer.
AB  - We have previously shown that patients with a positive family history of lung
      cancer did not exhibit characteristics expected if the familial association was a
      surrogate for a genetic mechanism which was absent in those without such a
      history. In this study, we examine the incidence of cancer (all sites) in two
      groups of families: (a) those ascertained through a patient with primary lung
      cancer (n = 359 families) and (b) through a community control subject (n = 234).
      The index subjects were excluded from all incidence data analyses. Most families
      (62 vs 57%) reported at least one member with a history of neoplastic disease.
      Patients' families were more likely to have 2 or more affected members (p less
      than 0.05), to exhibit a multigenerational pattern (33 vs 24%) and to have a
      higher risk of multiple tumours (OR = 1.5) in the same individual. However, most
      of the sites with the highest odds ratios (males, vocal cord/esophagus 8.3;
      colon/rectum 2.3; lung 1.96; females, pancreas 4.8; vocal/cord esophagus 4.1;
      lung 1.8) are smoking associated although these were not necessarily the most
      frequently affected sites. In conclusion, these data support an ecogenetic
      etiology of cancer within families.

PMID- 1986061
TI  - A consequence of omitted covariates when estimating odds ratios.
AB  - In the epidemiologic literature, one finds three criteria for confounding, which
      we will call the classical (marginal), operational (change-in-estimate) and
      conditional criteria. We define mavericks to be covariates that satisfy the
      operational criterion, but not the classical criterion. We present what is known
      about the problems of mavericks for estimating odds ratios and clarify the
      interpretation of odds ratios. Key results are: (1) omitting mavericks biases
      odds ratios towards 1; (2) omitting mavericks cannot artificially introduce an
      effect in contrast to omitting classical confounders; (3) the operational
      criterion for confounding corresponds to the conditional criterion when
      estimating odds ratios, but for relative risks, there are no mavericks (i.e. the
      classical and operational criterion correspond); and (4) the interpretation of
      odds ratios obtained from standard methods is that of comparing proportions, not
      of individual risk.

PMID- 1986062
TI  - Functional status and quality of life: predictors of early mortality among
      patients entering treatment for end stage renal disease.
AB  - We investigated the association between functional status and quality of life in
      newly-entered dialysis patients and the subsequent risk of mortality. We enrolled
      the patients from 37 dialysis facilities in two southeastern states (n = 294).
      Functional status was assessed by the Karnofsky Performance Scale (KPS) and
      quality of life by the Spitzer Quality of Life Index (SQLI). During a mean (SE)
      follow-up of 479.6 (109.4) days 49 patients (16.4%) of the cohort died. The mean
      KPS score (SE) for survivors was 7.31 (0.11) and for non-survivors was 5.89
      (0.26), P less than 0.0001. The mean SQLI score (SE) for survivors was 6.74
      (0.15) and non-survivors was 4.95 (0.28), P less than 0.0001. Strong gradients of
      the risk of mortality were found for both measurements. After controlling for
      other covariates including age, race, sex, primary cause of renal failure and the
      presence of comorbidity, both the KPS and SQLI scores were independently
      correlated with risk of mortality. We conclude that functional status and quality
      of life are strong independent risk factors for subsequent mortality in new
      dialysis patients. These are easily measured indicators which may serve to
      predict subsequent risk of mortality or adjust case-mix estimates for comparisons
      between dialysis populations.

PMID- 1986063
TI  - Mistakes in "established wisdom" about cigarette smoking?

PMID- 1986064
TI  - The posterior nervous system of the nematode Caenorhabditis elegans: serial
      reconstruction of identified neurons and complete pattern of synaptic
      interactions.
AB  - Serial-section electron microscopy has been used to reconstruct the cellular
      architecture of the posterior nervous system of the nematode Caenorhabditis
      elegans. Each of 40 neurons in the tail of the adult hermaphrodite can be
      reproducibly and unambiguously identified by a set of morphological features,
      including cell body position, fiber geometry and size, and staining properties. A
      complete list of synapses has been assembled for 2 isogenic animals, and these
      lists are compared with a third isogenic animal reconstructed by White et al.
      (1986). The set of neurons and their pattern of synaptic interactions is simple
      and reproducible. Most of the cells are involved in sensory transduction or in
      local signal processing to relay signals via a few interneurons to motoneurons
      and thence to body muscles. Because the tail neurons are well separated and
      fairly reproducible in position, the hermaphrodite tail lends itself to laser
      ablation studies of sensory processing (cf. Chalfie et al., 1985). Most of the
      synapses in the tail are concentrated in the preanal ganglion. Among the
      approximately 150 synapses there, about 85% are dyadic chemical synapses. The
      dyadic synapses are involved in reproducible patterns that have several
      interesting features. Most neurons synapse onto a few preferred pairs of target
      cells, in patterns that suggest a combinatorial model of synapse specification
      that may be open to genetic analysis. Furthermore, most dyadic contacts A----B,C
      fit a pattern in which the 2 postsynaptic partners are involved elsewhere in
      unidirectional synapses B----C. Thus, the dyadic synapse may serve to diverge
      sensory signals into parallel pathways, which then reconverge. This
      divergence/reconvergence pattern eventually directs processed sensory signals to
      the ventral cord interneurons PVCL and PVCR. About 80-90% of the synapses fall
      into repeated classes of synapses. Many of the remaining synapses are widely
      scattered and irreproducible from one animal to the next. Some of these contacts
      may be developmental mistakes reflecting a degree of "noise" in synapse
      specification (Waddington, 1957).

PMID- 1986065
TI  - Calcium activates two types of potassium channels in rat hippocampal neurons in
      culture.
AB  - Several calcium-dependent potassium currents can contribute to the
      electrophysiological properties of neurons. In hippocampal pyramidal cells, 2
      afterhyperpolarizations (AHPs) are mediated by different calcium-activated
      potassium currents. First, a rapidly activated current contributes to action
      potential repolarization and the fast AHP following individual action potentials.
      In addition, a slowly developing current underlies the slow AHP, which occurs
      after a burst of action potentials and contributes substantially to the spike
      frequency accommodation observed in these cells during a prolonged depolarizing
      current pulse. In order to investigate the single Ca2(+)-dependent channels that
      might underlie these currents, we performed patch-clamp experiments on
      hippocampal neurons in primary culture. When excised inside-out patches were
      exposed to 1 microM Ca2+, 2 types of channel activity were observed. In
      symmetrical bathing solutions containing 140 mM K+, the channels had conductances
      of 19 pS and 220 pS, and both were permeable mainly to potassium ions. The
      properties of these 2 channels differed in a number of ways. At negative membrane
      potentials, the small-conductance channels were more sensitive to Ca2+ than the
      large channels. At positive potentials, the small-conductance channels displayed
      a flickery block by Mg2+ ions on the cytoplasmic face of the membrane. Low
      concentrations of tetraethylammonium (TEA) on the extracellular face of the
      membrane specifically caused an apparent reduction of the large-channel
      conductance. The properties of the large- and small-conductance channels are in
      accord with those of the fast and slow AHP, respectively.

PMID- 1986066
TI  - Vault immunofluorescence in the brain: new insights regarding the origin of
      microglia.
AB  - The developmental appearance of ameboid and ramified microglia in the rat brain
      has been examined by immunofluorescent localization of vaults, recently described
      ribonucleoprotein particles (Kedersha and Rome, 1986a). Vaults are distinct,
      multiarched structures of unknown function expressed by higher and lower
      eukaryotic species. Although vaults have been detected in all mammalian cells
      examined to date, they are highly enriched in macrophages. In the brain, vault
      antisera is highly specific for both ameboid and ramified microglia. The
      developmental profile of vault immunoreactivity in rat brain slices suggests that
      microglia enter the brain at 2 locations, with different time scales for each.
      The first migration, which begins before embryonic day 15 and subsides between
      postnatal days 7 and 14, was identified by vault immunoreactivity and Bandeiraea
      simplicifolia B4-isolectin (a microglia marker) staining. The cells appear to
      enter from blood vessels and display a ramified morphology as soon as they are
      detected in the brain. The second microglial migration occurs in the first
      postnatal week, when ameboid microglia appear in the corpus callosum and other
      large fiber tracts. Ameboid microglia appear to differentiate into ramified
      microglia between postnatal days 4 and 14. Vault immunoreactivity, as a very
      early microglial marker, provides new insight regarding the much-debated origin
      of the ramified microglia. It is quite clear that ameboid cells are not the sole
      source of ramified microglia because ramified cells can be detected before the
      influx of ameboid microglia. Colocalization studies with monocyte/macrophage
      markers ED1 and OX42 demonstrate that both ramified and ameboid microglia
      originate from monocyte lineage.

PMID- 1986067
TI  - Developmental expression of REGA-1, a regionally expressed glial antigen in the
      central nervous system of grasshopper embryos.
AB  - Glial cells are a large component of the developing nervous system, appearing
      before the onset of axon outgrowth in a variety of developing systems. Their time
      of appearance and their location in conjunction with developing axon pathways may
      allow them to define the position of axon pathways. Specific glial cells may be
      utilized as guideposts by growing axons, allowing them to recognize the
      appropriate pathway, or conversely, glial cells may inhibit axons from growing
      along an inappropriate pathway. The 7F7 monoclonal antibody labels a subset of
      glial cells in grasshopper embryos that may play a role in defining the location
      of selected axonal pathways. This antibody recognizes the REGA-1 molecule, a cell
      surface antigen with a molecular weight of 60 kDa, which is regionally expressed
      on developing glial cells. REGA-1 is expressed around the edges of clusters of
      glial cells and on lamellae extending from glial cells to line the edges of some
      axonal pathways. REGA-1 expression is first seen in the neuroblast sheet,
      surrounding neuroblast 4-1. Slightly later in development, 2 glial cells extend
      processes that express REGA-1 and demarcate the caudal edge of the anterior
      commissure. As the animal matures, cell processes expressing REGA-1 line the
      edges of the longitudinal connective, then expand to surround the central
      neuropil of the segmental ganglia. REGA-1 expression is also seen in conjunction
      with axons leaving the segmental ganglia via the segmental nerves and the
      intersegmental connectives. REGA-1 expression is limited to a subset of glial
      cells; some known glial cells such as the segment boundary cell do not express
      REGA-1. Glial cell processes expressing REGA-1 are seen only in association with
      axons, which suggests that these processes may act as borders or guard rails
      confining axons to the appropriate regions of the developing CNS. Axons
      navigating a path through the CNS may be prohibited from growing into
      inappropriate regions based on their inability to cross the boundaries
      established by glial cells expressing REGA-1.

PMID- 1986068
TI  - Autoradiographic localization of putative nicotinic receptors in the rat brain
      using 125I-neuronal bungarotoxin.
AB  - Neuronal bungarotoxin (NBT), a snake venom neurotoxin, selectively blocks
      nicotinic receptors in many peripheral and central neuronal preparations. alpha
      Bungarotoxin (alpha BT), on the other hand, a second toxin isolated from the
      venom of the same snake, is an ineffective nicotinic antagonist in most
      vertebrate neuronal preparations studied thus far. To examine central nicotinic
      receptors recognized by NBT, we have characterized the binding of 125I-labeled
      NBT (125I-NBT) to rat brain membranes and have mapped the distribution of 125I
      NBT binding in brain sections using quantitative light microscopic
      autoradiography. The binding of 125I-NBT was found to be saturable, of high
      affinity, and heterogeneously distributed in the brain. Pharmacological studies
      suggested that more than one population of sites is labeled by 125I-NBT. For
      example, one component of 125I-NBT binding was also recognized by alpha BT, while
      a second component, not recognized by alpha BT, was recognized by the nicotinic
      agonist nicotine. The highest densities of these alpha BT-insensitive, nicotine
      sensitive sites were found in the fasciculus retroflexus, the lateral geniculate
      nucleus, the medial terminal nucleus of the accessory optic tract, and the
      olivary pretectal nucleus. alpha BT-sensitive NBT binding sites were found in
      highest density in the lateral geniculate nucleus, the subthalamic nucleus, the
      dorsal tegmental nucleus, and the medial mammillary nucleus (lateral part). The
      number of brain regions with a high density of 125I-NBT binding sites, blocked
      either by alpha BT or by nicotine, is low when compared with results obtained
      using other approaches to studying the central distribution of nicotinic
      receptors, such as labeling with 3H-nicotine or labeling with cDNA probes to
      mRNAs coding for putative receptor subunits. It is proposed that 125I-NBT labels
      a subpopulation of nicotinic receptors in the rat brain, and that, given its
      ability to block nicotinic receptors in a variety of neuronal preparations, NBT
      will be a useful probe for studying the functional properties of these sites.

PMID- 1986069
TI  - Photoinactivation of the crayfish segmental giant neuron reveals a direct giant
      fiber to fast-flexor connection with a chemical component.
AB  - The escape tail flip of the crayfish is "commanded" by 2 sets of giant-fiber (GF)
      interneurons. In each hemisegment, these drive the motor giant (MoG) abdominal
      flexor motor-neuron through a monosynaptic electrical connection, but the
      remaining 8 or 9 fast-flexor (FF) motorneurons receive most of their input via a
      disynaptic electrical pathway through the segmental giant (SG) neuron. We have
      investigated a monosynaptic GF-FF pathway, which operates in parallel to the
      disynaptic GF-SG-FF pathway, by using dye-mediated photoinactivation to remove
      the SGs from the tail-flip circuit. SG photoinactivation involves an initial
      broadening of the spike, leading to a long-duration, massively depolarized
      plateau. This is followed by loss of spike capability, a gradual reduction in the
      resting potential, and eventual total loss of electrical responsiveness. After
      bilateral photoinactivation of the SGs, a spike in one set of GFs, the medial
      giants (MGs), produces little if any effect in FFs in any ganglion. A spike in
      the other set, the lateral giants (LGs), produces an EPSP in FFs with a declining
      anterior-to-posterior segmental gradient in amplitude. These differences in LG
      and MG outputs, which are obscured in the intact circuit by the common MG/LG-SG
      FF pathway, give clues to a probable early evolutionary form of the circuit. The
      LG-FF connection in anterior ganglia has a significant electrical component.
      However, it also has an apparent monosynaptic chemical component, as revealed by
      the response to saline containing cadmium ions, and to cooling the preparation.
      This is the first physiological evidence for chemical output from a crayfish GF.

PMID- 1986070
TI  - Continuous repetitive stimuli are more effective than bursts for evoking LHRH
      release in bullfrog sympathetic ganglia.
AB  - Effects of different patterns of presynaptic stimulation upon release of
      leuteinizing hormone releasing hormone (LHRH) were studied by monitoring LHRH
      induced slow currents from individual postsynaptic neurons in bullfrog
      sympathetic ganglia. LHRH-mediated synaptic currents in ganglionic B and C
      neurons were recorded by a single-electrode voltage-clamp technique. Using
      continuous stimulation, release increased with frequency between 2 and 20 Hz,
      then declined. Though bursts of stimuli always evoked more release than
      continuous stimuli of the same average frequency, they were invariably less
      effective than continuous stimulation at the intraburstal frequency. This
      demonstrates that frequency, not bursting structure, governs peptide release. The
      dependence of release upon stimulus frequency was altered when extracellular Ca2+
      concentration was changed, implying that release does not depend intrinsically
      upon stimulation frequency, but simply on the availability of Ca2+.

PMID- 1986072
TI  - Status of cochlear implantation in children. American Academy of Otolaryngology
      Head and Neck Surgery Subcommittee on Cochlear implants.
AB  - The cochlear implant is a medical device, part of which is placed surgically,
      that uses electrical stimulation to provide hearing. For almost a decade,
      investigational studies have been ongoing to define its safety and efficacy in
      profoundly deaf children. During this period, more than 500 children aged 2
      through 17 years have been implanted with either a single-electrode or
      multielectrode device. Extensive auditory, speech, educational, and psychologic
      testing has been performed before and after implantation. Results show that the
      cochlear implant provides auditory detection over much of the speech signal.
      Compared with the preimplant period, there is significant improvement in auditory
      discrimination and speech production skills. Limited open-set word and sentence
      recognition is possible for at least some children. Complications with the device
      have been minimal. The cochlear implant can provide sound to deaf children unable
      to benefit from hearing aids. The complex assessment, rehabilitation, and parent
      counseling should be performed by centers with the multidisciplinary staffs
      necessary to provide effective care for patients with this specialized auditory
      prosthesis.

PMID- 1986071
TI  - Modification of leech behavior patterns by reserpine-induced amine depletion.
AB  - A single injection of 100 micrograms reserpine into the crop of the medicinal
      leech, Hirudo medicinalis, reduced CNS serotonin and dopamine levels to less than
      1% of control values within 3 d. High-pressure liquid chromotography- (HPLC)
      determined CNS serotonin and dopamine levels remained maximally depressed for
      approximately 1 month following reserpine injection. Subsequently, amine levels
      recovered slowly, but remained depressed 6 months after reserpine injection.
      Following reserpine treatment, glyoxylic acid-induced fluorescence or neutral red
      staining closely mirrored the HPLC-determined time course of amine depletion and
      recovery. Acute exposure of isolated ganglia to 10 microM reserpine for periods
      up to 6 hr produced a 20-30% reduction of serotonin and dopamine content. The
      threshold concentration of reserpine necessary to produce amine depletion was
      approximately 1 microM. We found that reserpine treatment eliminated biting
      behavior within 4 d following injection. Biting behavior remained depressed below
      control levels for approximately 4 months, but returned to control values while
      CNS serotonin and dopamine levels remained significantly depressed at this time.
      Unexpectedly, reserpine treatment increased rather than reduced the duration of
      stimulus-evoked swimming activity. This behavioral change was evident within 3 d
      and persisted for approximately 3.5 months. To rapidly restore amine levels in
      reserpine-treated animals, we bathed intact leeches in pond water containing
      serotonin, dopamine, or octopamine. We found that biting behavior was restored
      following reserpine treatment by bathing intact leeches in pond water containing
      serotonin or dopamine, but not octopamine. Also contrary to expectations, the
      increase in swim duration was not reversed by bath exposure to serotonin,
      dopamine, octopamine, or histamine. However, all swimming activity in reserpine
      treated leeches was eliminated by the amine antagonist cyproheptadine. We propose
      that the presence of low levels of amines is critical for the expression of both
      biting and swimming activity in leeches. However, the minimal levels of amines
      necessary for the expression of these behaviors are lower for swimming than for
      biting.

PMID- 1986073
TI  - Cardiac growth in fetuses of diabetic mothers with good metabolic control.
AB  - To evaluate cardiac growth in fetuses of those diabetic mothers with good
      metabolic control, we examined M-mode echocardiographic measurements obtained
      from 24 fetuses of diabetic mothers (FODM) and compared these with measurements
      from 31 normal fetuses of similar gestational age. Fetuses were grouped into
      three gestational periods: 20 to 26 weeks, 27 to 33 weeks, and 34 to 40 weeks.
      The mothers were believed to have good metabolic control on the basis of mean
      daily glucose profiles and glycosylated hemoglobin A (HbA1C) values of
      approximately 110 mg/dl (610 mumol/L) and 7.5%, respectively, before fetal
      scanning, and estimated fetal weight similar to that of normal fetuses during all
      three gestational periods. Both FODM and normal fetuses had significant increases
      in M-mode measurements from period 1 to period 3, but in FODM, cardiac
      hypertrophy developed by late gestation (period 3). This involved the
      interventricular septum (6.1 +/- 0.7 vs 4.9 +/- 0.3 mm, p less than 0.05), right
      ventricular free wall (5.7 +/- 0.8 vs 3.2 +/- 0.3 mm, p less than 0.01), and left
      ventricular free wall (6.4 +/- 0.6 vs 3.3 +/- 0.4 mm p less than 0.01). The
      interventricular septum/right ventricular free wall ratio was similar, whereas
      the interventricular septum/left ventricular free wall ratio in FODM was smaller
      by period 3 (1.0 +/- 0.1 vs 1.6 +/- 0.1, p less than 0.05). The right ventricular
      diastolic dimension was similar, but the left ventricular diastolic dimension was
      significantly smaller in FODM during periods 2 and 3 (8.2 +/- 1.2 vs 12.2 +/- 0.7
      mm, p less than 0.05). Strict metabolic control did not prevent FODM from having
      abnormal cardiac growth. We conclude that good metabolic control results in
      normal estimated fetal weight but that FODM remain at risk for mild global
      cardiac hypertrophy and altered diastolic dimensions.

PMID- 1986075
TI  - Management of infants at risk for occult bacteremia: a decision analysis.
AB  - Because febrile infants with no obvious source of bacterial infection may have
      bacteremia, and because bacteremia is difficult to diagnose on clinical grounds,
      we used decision analysis to evaluate whether such infants should be treated with
      antibiotics, tested further, or sent home. Using a simple decision tree, we found
      that the decision to give empiric antibiotic treatment is the decision of choice.
      The difference in quality-adjusted life expectancy between the "best" and "worst"
      decisions was only 11 days. However, this difference translated to prevention of
      death or permanent disability in 60 cases per 100,000 febrile children. Further,
      empiric treatment remained the best management alternative unless the probability
      of bacteremia was less than 1.4% (less than any published prevalence), or the
      efficacy of treatment was less than 21%. Our analysis demonstrated that a test
      with far greater sensitivity than leukocyte count or other tests currently in use
      is needed to justify testing rather than treating empirically. Further, an
      enormous patient population would be needed to find a difference of both clinical
      and statistical significance between treated and untreated patients in a
      controlled trial. In the absence of such trials, we recommend blood culture and
      empiric antibiotic treatment of all infants at risk for occult bacteremia.

PMID- 1986074
TI  - Asymmetric growth of the lateral cerebral ventricle in infants with
      posthemorrhagic ventricular dilation.
AB  - Lateral cerebral ventricular volume in 36 preterm infants with or without an
      intraventricular hemorrhage, and with or without posthemorrhagic hydrocephalus,
      was measured longitudinally and compared with the ventricular index measurements
      of the same ventricles. A poor correlation was found (r2 = 0.67). To determine a
      reason for this poor relationship, we analyzed the volumes of the regions of the
      ventricles by a segmental volume analysis. The occipital region of the lateral
      cerebral ventricle enlarged at a much faster rate (1.904 +/- 0.477 ml/day) than
      either the anterior region (0.546 +/- 0.253 ml/day; p less than 0.01) or the
      middle region (-0.209 +/- 0.334 ml/day; p less than 0.01) in infants with
      posthemorrhagic hydrocephalus. The rate of growth of the middle region of the
      lateral cerebral ventricles was the same for all infants. Linear indexes, such as
      the ventricular index and the lateral ventricular ratio, do not allow for
      accurate serial estimates of ventricular size in posthemorrhagic hydrocephalus
      because of asymmetric growth of the lateral cerebral ventricle. We conclude that
      sequential volume measurements are more useful than ventricular index
      measurements to follow ventricular size sequentially in infants with
      posthemorrhagic hydrocephalus.

PMID- 1986076
TI  - Controlled study of the effects of indomethacin on cerebral blood flow velocities
      in newborn infants.

PMID- 1986077
TI  - Adherence of cord blood neutrophils: effect of mode of delivery.

PMID- 1986078
TI  - A flow cytometric analysis of lymphocyte subpopulations in neonates undergoing
      extracorporeal membrane oxygenation.

PMID- 1986079
TI  - Glucose and insulin versus cation-exchange resin for the treatment of
      hyperkalemia in very low birth weight infants.

PMID- 1986080
TI  - Lovastatin therapy for cholesterol ester storage disease in two sisters.
AB  - We administered lovastatin to two sisters, aged 4 and 17 years, who had
      cholesterol ester storage disease, an autosomal recessive disorder manifested by
      hypercholesterolemia and hypertriglyceridemia. The drug, a competitive inhibitor
      of 3-hydroxy-3-methylglutaryl coenzyme A reductase, was taken orally for 6
      months. Serum lipid concentrations were determined monthly. Computed tomography
      of the liver was performed before and during therapy to evaluate liver fat
      content. The younger sister had liver biopsies before and after 6 months of
      lovastatin therapy to assess hepatic cholesterol stores. Both patients had marked
      decreases in serum levels of cholesterol, triglycerides, and low-density
      lipoprotein-cholesterol; high-density lipoprotein-cholesterol levels increased.
      Computed tomography during treatment demonstrated a significant increase in
      linear attenuation, suggesting a decreased liver fat content. Liver tissue
      obtained 6 months after lovastatin therapy was initiated had 13% less esterified
      cholesterol than the liver sample obtained before treatment. We conclude that
      lovastatin may be effective in treating children with cholesterol ester storage
      disease.

PMID- 1986082
TI  - Misinterpretation of iron-binding capacity in the presence of deferoxamine.

PMID- 1986081
TI  - Hematin therapy for the neurologic crisis of tyrosinemia.

PMID- 1986083
TI  - Long-term chloroquine-proguanil malaria prophylaxis in a nonimmune pediatric
      population.

PMID- 1986084
TI  - Estimates of metabolic rate in obese and nonobese adolescents.
AB  - To evaluate the validity of equations for the calculation of basal metabolic
      rate, we compared measured metabolic rates in a population that included obese
      and nonobese adolescents with metabolic rates calculated from five equations
      commonly used to estimate metabolic rate. Of the available options, neither the
      Mayo Clinic nomogram nor the Food and Agriculture Organization/World Health
      Organization/United Nations University (FAO/WHO/UNU) equations produced estimates
      that differed significantly from measured values. In a second cohort of severely
      obese adolescent girls, the FAO/WHO/UNU equation that included both height and
      weight provided the most accurate estimate of metabolic rate. Because of their
      simplicity, we recommend use of the FAO/WHO/UNU equations to estimate metabolic
      rate in adolescent populations (boys: BMR = 17.5 weight (kg) + 651; girls: BMR =
      12.2 weight (kg) + 746). However, when obese cohorts are studied, the FAO/WHO/UNU
      equation that includes both weight and height predicts metabolic rate most
      accurately (boys: BMR = 16.6 weight (kg) + 77 height (m) + 572; girls: BMR = 7.4
      weight (kg) + 482 height (m) + 217).

PMID- 1986086
TI  - Role of general pediatricians in adolescent health care.

PMID- 1986085
TI  - "Crack" use by American middle-class adolescent polydrug abusers.
AB  - A 77-item questionnaire on cocaine and "crack" use patterns, and on the
      addictive, medical, and criminal consequences of such use, was completed by 464
      largely white, middle-class, suburban, teenage drug abusers registered in seven
      geographically disparate outpatient treatment facilities. Of the 130 (28%) who
      smoked crack, 87 (67%) were designated as "experimenters" (use of crack 1 to 9
      times); 20 (15%) were in an intermediate group (smoked crack 10 to 50 times); and
      23 (18%) were heavy users (smoked crack more than 50 times). Sixty percent of
      heavy users progressed from initiation of crack use to its use at least once a
      week in less than 3 months. Almost 50% of the 87 experimenters and nearly all the
      23 heavy users recalled preoccupation with thoughts of crack, rapid loss of the
      ability to modulate their use of the drug, and rapid development of pharmacologic
      tolerance. Suspiciousness, mistrust, and depressed mood were associated with the
      increasing use of crack. Seizures occurred in none of those who used cocaine by
      snorting it intranasally (without ever smoking crack), in contrast to 1% of the
      experimenters and 9% of the 43 respondents who had smoked crack at least 10
      times. Seven percent of the 87 experimenters versus almost one fourth of the 43
      who smoked crack more frequently had injected cocaine intravenously. The use of
      crack by middle-class adolescents is associated with rapid addiction and with
      serious behavioral and medical complications.

PMID- 1986087
TI  - Haemophilus conjugate vaccine and Guillain-Barre syndrome.

PMID- 1986088
TI  - Prenatal and perinatal factors in the etiology of cerebral palsy.

PMID- 1986089
TI  - Use of acyclovir for varicella.

PMID- 1986090
TI  - Cancers in children infected with human immunodeficiency virus.

PMID- 1986091
TI  - Human figure drawings and sexual abuse.

PMID- 1986092
TI  - Growth hormone for normal short children.

PMID- 1986094
TI  - Maternal use of cocaine during pregnancy and congenital cardiac anomalies.

PMID- 1986093
TI  - Relationship of physical activity to blood pressure and body weight.

PMID- 1986095
TI  - Human milk secretory immunoglobulin A to Shigella virulence plasmid-coded
      antigens.
AB  - Although antibodies to the lipopolysaccharide antigens of Shigella have been
      demonstrated in human milk, such antibodies do not explain the putative
      protective effect of breast-feeding against symptomatic Shigella infection.
      Shigella species do not share related lipopolysaccharides, but they do possess
      closely related virulence plasmids that code for the proteins essential for cell
      invasion. We therefore sought to determine the frequency, amount, and duration of
      excretion of human milk antibodies to these shared virulence plasmid-associated
      antigens in populations of different rates of Shigella infection frequency
      (Mexico City, high; Houston, low). Such antibodies were present in the milk of
      virtually all the Mexican women but also were present in a large proportion of
      milk samples from the women living in Houston. The amounts of these antibodies
      were highest in colostrum but after 2 weeks of lactation fell to stable levels.
      The frequency and persistence of these antibodies in the milk of the women from
      Houston suggest that the memory and drive for secretion of these antibodies is
      extremely long lived.

PMID- 1986096
TI  - Impact of dietary cereal on nutrient absorption and fecal nitrogen loss in
      formula-fed infants.
AB  - STUDY OBJECTIVE: To determine the capacity of infants to digest and absorb rice
      cereal and to determine the effect of cereal feeding on total energy and nitrogen
      absorption. SETTING: Subject's residences and the Texas Children's Hospital
      Clinical Research Center, Houston. PATIENTS: Eight healthy 1-month-old bottle-fed
      infants. INTERVENTIONS: Infants were fed their usual formula for 3 days. For the
      subsequent 6 days, they received 4 gm of rice cereal, labeled with carbon 13, per
      30 ml of the formula. MEASUREMENTS AND MAIN RESULTS: Fecal balance studies were
      performed for a 72-hour period while the infants received only formula and again
      during the last 3 days of cereal feeding. Breath samples for hydrogen measurement
      were collected before and after the cereal feeding. Nutrient intake was measured
      and stools were analyzed for 13C abundance, energy, nitrogen, fiber content, and
      bacterial mass. Cereal absorption was 88 +/- 9% (mean +/- SD). Despite a
      significant increase in energy and nitrogen intake from cereal feeding, the
      coefficient of absorption fell (energy: 97% to 90%, p = 0.048; nitrogen: 94% to
      74%, p = 0.009). Fecal dry weight increased after the cereal feeding (p = 0.004),
      primarily as a result of a sevenfold increase in fecal bacterial mass (p =
      0.002). Fecal nitrogen increased primarily because of incorporation of nitrogen
      into bacteria. No differences were detected in breath hydrogen as a consequence
      of formula feeding versus formula-cereal feeding. CONCLUSIONS: Although cereal
      was relatively well-absorbed in this group of infants and increased their intakes
      of energy and nitrogen, it did not increase the coefficients of energy and
      nitrogen absorption. Cereal feeding increased fecal bacterial mass and bacterial
      nitrogen.

PMID- 1986097
TI  - Cardiovascular abnormalities in infants prenatally exposed to cocaine.
AB  - This study utilized a historical cohort to examine the relationship between
      maternal cocaine use during pregnancy and the occurrence of congenital
      cardiovascular abnormalities. All neonatal drug screens performed at Boston City
      Hospital during an 18-month period were reviewed (n = 554); for 214 (39%)
      screened high-risk neonates, results of toxicologic screens were positive for
      cocaine, and 340 (61%) neonates had no detectable cocaine. We compared the
      occurrence of cardiovascular malformations and electrocardiographic abnormalities
      in these two groups. Matches were sought between these 554 infants and our
      pediatric cardiology data base, which consisted of inpatient consultation,
      outpatient consultation, and electrocardiography. Forty-nine patients had drug
      screens and were also entered into our cardiology data base: 25 had both
      consultations and electrocardiograms, and 24 had electrocardiograms only. The
      rate of cardiac anomalies among the cocaine-positive infants was significantly
      higher (relative risk = 3.7; 95% confidence interval: (1.4, 9.4)) than the rate
      of these anomalies among the cocaine-negative comparison group (65/100 vs
      18/1000); the rate for cocaine-positive infants was also significantly higher
      than published rates for general populations of infants. Several
      electrocardiographic abnormalities, high-grade ventricular ectopy, and
      cardiorespiratory arrests were also noted in our study population. We conclude
      that cocaine exposure during prenatal life appears to predispose infants to
      structural cardiovascular malformations, electrocardiographic abnormalities, and,
      possibly, cardiopulmonary autonomic dysfunction.

PMID- 1986098
TI  - Phenotypic variability in glutaric aciduria type I: Report of fourteen cases in
      five Canadian Indian kindreds.
AB  - We describe 14 patients with glutaric aciduria type 1 in five Canadian Indian
      kindreds living in Manitoba and northwest Ontario. The patients had marked
      clinical variability of the disease, even within families. Eight followed the
      typical clinical course of normal early growth and development until the onset of
      neurologic abnormalities, often precipitated by infection, between 6 weeks and 7
      1/2 months of age. Five patients had early developmental delay; one was thought
      to be normal until 8 years of age. Three patients died, seven are severely
      mentally and physically handicapped, and four have only mild mental retardation
      or incoordination. Six patients had macrocephaly in the neonatal period. Computed
      tomography was done for 12 patients, and findings were abnormal in 11. Glutaric
      acid and 3-hydroxyglutaric acid were detected in increased amounts in the urine
      of all patients, but the concentrations were much lower than those in most other
      reported patients. Glutaryl coenzyme A dehydrogenase activity in skin
      fibroblasts, interleukin-2-dependent lymphocytes, or both, ranged from 0% to 13%
      of control values. There was no correlation between clinical severity and urine
      glutaric acid concentration or level of residual enzyme activity. We recommend
      that organic acid analysis of the urine be done in patients with unexplained
      cerebral palsy-like disorders, especially if the computed tomographic scan is
      abnormal. If there is suspicion of glutaric aciduria, glutaryl-coenzyme A
      dehydrogenase should be measured in fibroblasts or lymphocytes even if glutaric
      acid is not increased in the urine.

PMID- 1986099
TI  - Treatment of childhood angiomatous diseases with recombinant interferon alfa-2a.
AB  - A heterogeneous group of five patients with progressive, invasive angiomatous
      diseases including pulmonary hemangiomatosis, angiosarcoma, or massive hemangioma
      with associated consumptive coagulopathy were treated with interferon alfa-2a for
      periods of 17 to 33 months. One patient with a large thoracic hemangioma,
      cardiorespiratory failure, and consumptive coagulopathy died after less than 2
      months of treatment. The remaining four patients have shown beneficial responses,
      including (1) regression of abnormal vessels on pulmonary angiogram and improved
      exercise tolerance in pulmonary hemangiomatosis (two patients), (2) decreased
      corticosteroid and/or platelet transfusion requirements in consumptive
      coagulopathy (two patients), and (3) decreased size and number of tumor nodules
      in the one patient with angiosarcoma arising in preexisting angiomatous lesions.
      Responses occurred during periods of 2 to 20 months of treatment. There was no
      measurable progression of angiomatous lesions in any patient receiving interferon
      at the therapeutic dose, except possibly in the one who died. Each of the four
      surviving patients had improved linear growth and weight gain during interferon
      treatment.

PMID- 1986100
TI  - Clinical decisions: how much analysis and how much judgment?

PMID- 1986101
TI  - Immunogenicity of Haemophilus influenzae type b polysaccharide-diphtheria toxoid
      conjugate vaccine in 3- to 17-month-old infants with sickle cell diseases.

PMID- 1986102
TI  - Anaphylaxis to casein hydrolysate formula.

PMID- 1986103
TI  - Anaphylaxis after ingestion of a recently introduced hydrolyzed whey protein
      formula.

PMID- 1986104
TI  - Growth of human milk-fed and formula-fed infants with cystic fibrosis.

PMID- 1986105
TI  - America's lost children: whose responsibility?

PMID- 1986106
TI  - Excretion of human immunodeficiency type 1 in the throat but not in urine by
      infected children.

PMID- 1986107
TI  - Lung disease associated with IgG subclass deficiency in chronic mucocutaneous
      candidiasis.

PMID- 1986108
TI  - Omenn phenotype with short-limbed dwarfism.

PMID- 1986109
TI  - Pseudodominant transmission of an autosomal recessive disease, adenine
      phosphoribosyltransferase deficiency.

PMID- 1986110
TI  - 5-Oxoprolinuria in an adolescent with chronic metabolic acidosis, mental
      retardation, and psychosis.

PMID- 1986111
TI  - Massive transfusion: outcome in blunt trauma patients.
AB  - Over a 54-month period 6,142 patients were consecutively admitted to our Level I
      trauma center. Ninety-two blunt trauma patients required massive transfusion (MT)
      of 20 or more units of packed red blood cells (range, 20-126). Eighty-two per
      cent of all transfused blood was given within 24 hours of admission. Forty-eight
      patients (52%) were long-term survivors. Twenty-six patients died (28%) within 24
      hours and 21 of these exsanguinated. Eighteen patients died greater than 24
      hours: nine (50%) died from multiple organ failure, and nine (50%) died from
      severe closed head injury (CHI). Clinical predictors of increased mortality were:
      shock on admission, closed head injury, and age. Forty-three survivors were
      followed for a mean of 2.5 years (range, 1-5 years). No patient died during
      followup. All patients were home at 1 year; only four patients required continued
      medical assistance. Thirty-two patients (74%) returned to work. We conclude that:
      1) blunt and penetrating trauma patients receiving MT have similar survival rates
      of 50%; 2) shock, closed head injury, and age predict increased mortality but do
      not preclude survival; 3) long-term outcome in blunt patients requiring MT is
      excellent. Post-discharge death is rare and 3/4 of the survivors return to work,
      justifying the high cost of acute care.

PMID- 1986112
TI  - Trauma case manager development and implementation as a nursing role in a
      community trauma center.

PMID- 1986113
TI  - How to save fuel and reduce injuries in automobiles.
AB  - Increased fuel economy and reduced injuries have been portrayed as incompatible
      goals, based on the false assumption that vehicle weight is the determining
      factor in both. Physics predicts that size and velocity, not weight, are the
      primary factors affecting crash forces, while increased weight or increased
      velocity consumes more fuel. Analysis of fatal injury rates, injury costs, and
      fuel use relation to vehicle weight, vehicle size, and engine horsepower confirms
      that weight is of minimal importance in injury severity compared to the other two
      factors. Fuel use is a function of weight and horsepower. Injuries and fuel use
      can be reduced by reducing vehicle horsepower without changing vehicle size.

PMID- 1986114
TI  - High-pressure injection injuries of the hand.
AB  - The majority of high-pressure injection injuries can produce serious damage to
      the hand. Nevertheless, the injury may follow a relatively benign course if the
      injected substance possesses a less harmful nature. Treatment for these injuries
      requires immediate and aggressive surgery in most circumstances, but conservative
      treatment may be justified in certain instances. During a 4-year period, eight
      cases of high-pressure injection injury were encountered. The types of injected
      material were: four from paint, and one each from grease, water, benzene, and
      hydraulic oil. Time is an important factor regarding the results, while the types
      of injected material modify the clinical courses. It is advisable that the
      etiology of high-pressure injection injury should be established initially, and
      this factor be taken into consideration in choosing treatment options.

PMID- 1986115
TI  - Primary intramedullary nailing of open femoral shaft fractures.
AB  - The cases of 60 patients with 63 open femoral fractures treated by primary reamed
      intramedullary nailing were retrospectively reviewed. Twenty-two were classified
      as Type I open fractures, 26 as Type II and 15 as Type III open fractures by
      Gustilo's classification. All fractures were treated by wound debridement
      followed by immediate reamed intramedullary nailing. There were five early soft
      tissue infections and three late deep infections. Of the late infections, only
      one was osteomyelitis (1.6%). There were three nonunions and seven malunions. All
      of the complications were dealt with effectively by standard methods. We
      concluded that primary reamed intramedullary nailing is an effective alternative
      for the treatment of Type I and II open femur fractures and for Type III open
      femur fractures associated with multiple trauma.

PMID- 1986116
TI  - Post-traumatic bile fistulae.
AB  - Bile leakage after liver injury has been reported to be a complication associated
      with significant mortality. In a prospective study of 306 patients with liver
      injuries 13 (4%) developed a bile leak. There appear to be two groups of
      patients, those with a major bile duct injury (three patients) and those with a
      more peripheral injury (ten patients). Bile leaks may present either as bile
      peritonitis (six patients) or as a bile leak through a drain site (seven
      patients). All but one bile leak closed spontaneously at a median of 33 days
      (range, 3-110 days). There was no mortality but patients incurred a median of
      four complications each (range, 1-5). This may reflect the severity of the
      initial injury rather than the bile leak. Respiratory failure and/or infection
      and sepsis were the most common complications whilst abnormalities of liver
      function, although common, were seldom of clinical significance.

PMID- 1986117
TI  - A prospective evaluation of the AO/ASIF universal femoral nail in the treatment
      of traumatic and reconstructive problems of the femur.
AB  - Beginning in October 1986, we prospectively evaluated the AO/ASIF Universal
      Femoral Nail in the treatment of traumatic (89 nails) and reconstructive (11
      nails) problems of the femur. For treatment of isolated femoral fractures, the
      mean time of patient positioning and nail insertion was 2.4 hours with a mean
      blood loss of 389 ml. Seventy-eight per cent of the patients were followed for a
      minimum of 12 months. There were no infections, one case of nail failure, two
      cases of screw fracture, and three nonunions. Sixteen nails have been
      uneventfully removed. The AO/ASIF femoral nail provides results comparable to
      other intramedullary interlocking devices.

PMID- 1986118
TI  - Injuries to the cervical spine causing vertebral artery trauma: case reports.
AB  - In four patients with lesions of the vertebral artery resulting from cervical
      spine injury, two were due to unilateral facet dislocation and two to fractures
      of the dens. There was one arterial occlusion with minor vertebrobasilar
      symptoms, and an arterial lesion with thrombosis causing embolic occlusion of the
      basilar artery with lethal outcome. In one patient a fresh fracture of the dens
      caused dislocation of C1/2 with reversible occlusion of the left and stenosis of
      the right vertebral artery, resulting in unconsciousness. In a patient with
      pseudarthrosis of the dens an aneurysm of the vertebral artery could be detected.
      Cerebellar or cerebral symptoms associated with cervical spine injury should be
      investigated by vertebral angiography because vertebral arterial injury may be
      more common than suspected and may simulate traumatic brain damage.

PMID- 1986119
TI  - Traumatic rupture of the interventricular septum and tricuspid valve: case
      report.
AB  - Cardiac injury following blunt trauma is an important cause of morbidity and
      mortality and is often unsuspected. Isolated chamber rupture and valvular injury
      are infrequent but recognized consequences of nonpenetrating trauma. This report
      describes a patient who developed a perimembranous ventricular septal defect and
      disruption of the septal leaflet of the tricuspid valve as a consequence of blunt
      trauma. Diagnosis and management of traumatic ventricular septal rupture are
      discussed.

PMID- 1986121
TI  - Penetrating injury of a duplicated ureter: case report.
AB  - Duplications of the genitourinary tract are uncommon and may be a source of
      confusion in the early diagnosis of ureteral trauma when their presence is not
      suspected. We present a case of delayed diagnosis of a penetrating injury to a
      duplicated ureter and its management.

PMID- 1986120
TI  - Bullet fragment venous embolus to the heart: case report.
AB  - This report describes a case of bullet fragment embolus to the heart following a
      small-caliber gunshot wound to the mouth. Skull and C-spine films appeared to
      account for the projectile; however, chest X-ray followed by fluoroscopy and two
      dimensional echocardiography demonstrated a venous missile embolus in the right
      heart. The bullet was palpated, trapped in the right ventricle, and easily
      extruded.

PMID- 1986122
TI  - Intrahepatic arterioportal fistula after blunt hepatic trauma: case reports.
AB  - Intrahepatic arterioportal fistula (APF) was found in five out of 65 consecutive
      patients following blunt hepatic trauma. In four patients the fistula was located
      peripherally and the blood flow was small. These fistulas closed spontaneously
      within 3 months. However, a centrally located fistula with early visualization of
      the trunk of the portal vein persisted in one patient and necessitated
      transcatheter embolization. The APF in this patient caused portal dilatation
      which was detectable by CT scan. We conclude that spontaneous closure can be
      expected when an APF is located peripherally and the shunt flow is small, while
      centrally located APF with large flow require active treatment, preferably by
      transcatheter embolization. An APF detectable by CT scan suggests the need of
      intervention.

PMID- 1986123
TI  - Traumatic scapulothoracic dissociation: case report.
AB  - A 23-year-old man suffered traumatic scapulothoracic dissociation (TSD) in a car
      vs.-bicyclist accident. TSD is a devastating forequarter injury characterized by
      brachial plexus damage, major upper extremity musculoskeletal disruption, and
      exsanguinating hemorrhage: our patient survived a hematocrit of 7. Prompt
      recognition and aggressive management of TSD's multiple injuries are crucial.

PMID- 1986124
TI  - The management of mid-face fractures with intracranial injury.
AB  - Recent advances have radically changed the management of facial fractures. CT
      scanning, extensive exposure, and rigid plate fixation in the setting of the
      trauma center have permitted early operation with improved results. A subset of
      patients with facial fractures will also have intracranial injuries (ICI). We
      sought to identify parameters associated with an increased risk for ICI. We also
      sought to examine the safety and limits of early craniofacial repair in patients
      with intracranial injuries. Of 114 mid-face fractures treated over a 1-year
      period, 43 (38%) had a concomitant ICI. The majority, 36 (84%), were from motor
      vehicle accidents (MVA). Frontal sinus and orbitoethmoid fractures were at the
      highest risk for ICI, although orbitozygomatic fractures caused by MVAs also had
      a surprisingly high incidence of ICI. Our results show that early craniofacial
      repair can be performed safely with appropriate general surgical and
      neurosurgical support.

PMID- 1986125
TI  - Compressed air injury to the esophagus: case report.

PMID- 1986126
TI  - Ski fatalities in Vermont.

PMID- 1986127
TI  - Emergency center ultrasonography in the evaluation of hemoperitoneum: a
      prospective study.
AB  - The reliability of ultrasonographic detection (US) of hemoperitoneum in blunt
      abdominal trauma was evaluated in a prospective study of 72 patients. Independent
      of the examiner, sensitivity, specificity, and accuracy were, respectively,
      86.7%, 100%, and 97.2%. Laparotomy was indicated in 76.9% of US hemoperitoneum
      positive cases. No negative laparotomies were performed in this study group. If
      hemoperitoneum is revealed in US and vital signs are unstable, we think
      laparotomy is indicated. We believe that US in an emergency center is a quick,
      safe screening method in the evaluation of blunt abdominal trauma. US might take
      over a great part of the role of diagnostic peritoneal lavage.

PMID- 1986128
TI  - Multipiece tire rim injuries.
AB  - Multipiece tire rims can explode during tire change, causing severe injury.
      Although more than 450 such accidents, with at least 80 deaths, have been
      recorded by the National Highway Traffic Safety Administration (NHTSA), we found
      no reports in the surgical literature on such injuries in the United States. This
      report describes experience with seven patients who sustained injuries in
      explosions of multipiece tire rims. All victims suffered massive maxillofacial
      trauma with associated ocular, cranial, intracranial, and extremity injuries. Two
      patients died, both because of intracerebral hemorrhage. One patient suffered
      serious long-term disability. All survivors required extensive reconstructive
      surgery. The design of the multipiece tire rim is inherently hazardous. Since
      many accidents of this type are not reported to the NHTSA, the incidence of such
      injuries may be significantly higher. An alternative, nonhazardous tire rim is
      available. Design modifications or a law restricting use of multipiece tire rims
      would prevent many accidents.

PMID- 1986129
TI  - Improved outcome with early fixation of skeletally unstable pelvic fractures.
AB  - Thirty-seven consecutive patients with unstable pelvic fractures were divided
      into two groups: Group 1 (July 1981 to December 1984; n = 18), when early
      fixation was not routinely used, and Group 2 (January 1985 to March 1988; n =
      19), when early fixation was performed unless contraindicated. Hospital stay
      decreased by 37.8% in Group 2 (p = 0.04). Of Group 1 patients, 60% were disabled
      for at least 6 months versus 15.7% in Group 2 (p = 0.001), and 45% were
      discharged to a rehabilitation facility versus 26.4% in Group 2. Group 1 had more
      complications, 1.3 per patient, versus 1.0. Patients in Group 2 (undergoing early
      fixation) required 27.2% fewer units of blood than those in Group 1 in whom
      fracture surgery was delayed. Survival was better in Group 2, 100% versus 83.3%
      (p = 0.06). Early pelvic fracture fixation reduces hospital stay, long-term
      disability, and may result in fewer complications, decreased blood loss, and
      better survival.

PMID- 1986130
TI  - Heat loss in an animal experimental model.
AB  - Heat loss leading to hypothermia is common during surgery, particularly when a
      body cavity is exposed. To determine the principal site of heat loss we used heat
      flux transducers to measure heat loss from the skin and the exposed abdominal
      cavity of seven pigs. Heat loss from the skin was 74 +/- 15 W/m2, and from the
      abdominal cavity, 350 +/- 122 W/m2 (p less than 0.002; ratio = 1:4.7). The area
      of the skin was 0.52 +/- 0.06 m2, and of the abdominal cavity, 0.04 +/- 0.006 m2
      (ratio = 13.6:1). For every 13.6 watts lost from the skin, 4.7 watts were lost
      from the abdominal cavity; i.e. skin heat loss accounted for 74% of total heat
      loss. Therefore adequate insulation would reduce the incidence of hypothermia.
      Evaporation accounted for the largest heat loss from the abdominal cavity.
      Evaporative losses could be minimised by enclosing the bowel in a plastic bag.

PMID- 1986131
TI  - A statewide profile of general surgery trauma practice.
AB  - This study profiles the practices, experience, and viewpoints of general surgeons
      treating trauma patients throughout a state. A mail survey of the American
      College of Surgeons State Chapter membership was conducted. Response rate of
      general surgeons was 65%. Typically, the trauma surgeon is between 30 and 50
      years old, having received formal trauma experience through residency training
      only. Thirty-nine per cent report current ATLS certification. Practices are most
      commonly based at a community hospital in an urban setting. Half of surgeons
      treating trauma operate at more than one hospital and nearly a third take call at
      more than one hospital simultaneously. Eighty-seven per cent of respondents
      reported trauma patients comprise less than one quarter of their practice. Most
      (68%) admitted fewer than 25 trauma patients to their service in the year before
      the survey and 78% reported performing less than ten trauma laparotomies in the
      prior year. Fifty-eight per cent disagree that every general surgeon should
      routinely manage major trauma and 83% feel that traumatology entails a specific
      body of knowledge and expertise. Of the various components of trauma care, the
      role of the surgeon in trauma prevention and administrative duties was ranked at
      least important. The areas of surgeon availability, uniformity of basic
      experience and adequate maintenance of skills need further analysis.

PMID- 1986132
TI  - Spine trauma and associated injuries.
AB  - A longitudinal, prospectively gathered data base of spine trauma has been
      developed. A review of 508 consecutive hospital admissions identified the
      presence of associated injuries in 240 (47%) individuals, most frequently
      involving head (26%), chest (24%), or long bones (23%). Twenty-two per cent had
      one associated injury, 15% had two, and 10% had three or more. Most spine
      fractures involved the lower cervical (29%) or thoracolumbar junction (21%).
      Comparisons of presence or absence of associated injuries and spine fracture
      level showed significant differences (p less than 0.001). Eighty-two per cent of
      thoracic fractures and 72% of lumbar fractures had associated injuries compared
      to 28% of lower cervical spine fractures. While there was no significant
      relationship between type of associated injury and spine fracture level, those
      with associated injuries were less likely to have a neural deficit (p less than
      0.05). After hospital admission, there were seven deaths. Early assessment and
      transport of spine trauma victims must be carried out with appropriate management
      of associated injuries. Conversely, multiple trauma victims must be handled with
      due regard for a possible spine fracture. The value of spinal units with
      specially trained personnel is emphasized.

PMID- 1986133
TI  - Locked intramedullary nailing of femoral shaft fractures.
AB  - One hundred twenty-three femoral shaft fractures were treated with Grosse-Kempf
      slotted, locked nails and followed for a median 20 (range, 12-60) months. There
      were eight intraoperative and 11 postoperative complications, among them two
      superficial and two deep infections. Most of the intraoperative complications and
      some postoperatively lost reductions could have been prevented by a better
      operative technique and judgment of stability. Seventy-eight results were graded
      as excellent, 24 as good, 19 as fair, and two as poor (one 9-cm shortening and
      one 40 degrees external malrotation). All fractures united without further
      procedures during the first year.

PMID- 1986134
TI  - The epidemiology of seatbelt-associated injuries.
AB  - This study examined the frequency of spine and abdominal injuries to motor
      vehicle occupant crash victims, the relationship between the two types of
      injuries, and the association with restraint use. There were 303 motor vehicle
      occupants treated at a regional trauma center for spine and/or abdominal injuries
      over a 5-year period. Patients with Chance-type fractures of the lumbar spine
      were much more likely to be rear seat passengers and to be using a lap belt than
      were patients with other types of spinal injuries. Similarly, patients with
      hollow viscus injuries were more likely to be rear seat passengers and to be lap
      belted than were patients with injuries to the spleen, liver, pancreas, or
      kidneys. Nearly two thirds of the lumbar Chance-type fractures were associated
      with hollow viscus injuries, including six of seven children. This increased risk
      of Chance-type fractures and hollow viscus injuries was associated with increased
      use of lap-belt seat restraints in the population.

PMID- 1986135
TI  - Impairment of specific host defense mechanisms in patients with chronic post
      traumatic osteomyelitis.
AB  - We studied both in vivo and in vitro specific host defense mechanisms in patients
      suffering from chronic post-traumatic osteomyelitis (n = 26). The cell-mediated
      immunity in vivo was impaired as indicated by the reduced reactivity in the
      delayed type hypersensitivity skin test. The concanavalin A or phytohemagglutinin
      induced T-cell proliferation in vitro was markedly decreased in comparison to
      healthy donors. In contrast, B-cell proliferation stimulated by Staphylococcus
      aureus Cowan I was not altered. While the absolute lymphocyte counts and the
      percentage of T, B, and O cells were within the normal range, nine out of the 26
      patients showed a significantly diminished ratio of CD4+ and CD8+ T cells.
      Humoral immunity in the patients was less affected as assessed by the unchanged
      serum levels of immunoglobulins (Ig). However, the T-cell dependent polyclonal Ig
      synthesis after in vitro stimulation with pokeweed mitogen was suppressed. Our
      results provide evidence that cell-mediated immune functions are predominantly
      impaired in patients with post-traumatic osteomyelitis which may contribute to
      the persistence of the localized bone infection.

PMID- 1986136
TI  - Risk factors for multiorgan failure: a case-control study.
AB  - The aim of this study was to identify factors associated with Multiple Organ
      Failure (MOF), and assess possible interactions between the risk factors
      identified as such. We studied 40 MOF cases and 120 controls, out of all the
      surgery and trauma patients who needed intensive care at our institution in a 24
      month period. The univariate analyses showed that age, hypovolemic shock, massive
      volume administration (MVA), sepsis, and time of evolution before arriving to the
      hospital (TE) were significantly associated with MOF. Logistic regression
      analysis showed that neither age nor MVA were independently associated with MOF
      after adjusting for all of the other variables. Interactions seemed to be present
      between age, sepsis, and shock. We conclude that in our surgery and trauma ICU
      adult patient population, hypovolemic shock, sepsis, and TE are independent risk
      factors for MOF. The importance of the association between shock and sepsis is
      discussed, as well as the possible relevance of TE as a risk factor.

PMID- 1986137
TI  - Hypertonic saline alters plasma clotting times and platelet aggregation.
AB  - Hypertonic (7.5%) saline (HS) is advocated for resuscitation of injured and
      burned patients. Recent animal studies indicate that HS increases bleeding during
      uncontrolled hemorrhage, although the mechanisms for this are unclear. To
      investigate potential anticoagulant effects of HS (without dextran), normal human
      plasma was serially diluted with either HS or normal (0.9%) saline (NS).
      Prothrombin times (PT), activated partial thromboplastin times (APTT), and
      platelet aggregation studies were performed. Significant (p less than 0.05)
      deteriorations in clotting tests and platelet aggregation developed when 10% or
      more of normal plasma was replaced by HS, whereas there was no effect from
      similar NS dilutions. Strong correlations were observed between clotting test
      changes and sodium concentrations (R2 greater than 0.80, p less than 0.0001).
      Thus, HS exhibits anticoagulant activity, but not at the usual small volumes
      necessary to produce hemodynamic improvement. Nevertheless, the anticoagulant
      effect may be more pronounced with ongoing clotting factor losses or with the
      addition of dextran.

PMID- 1986138
TI  - Improvement of septic syndrome after administration of recombinant human growth
      hormone (rhGH)?
AB  - Twenty patients with generalized sepsis were studied prospectively to evaluate
      the effects of recombinant human growth hormone (rhGH) administration. Five
      patients had developed sepsis after major abdominal surgery, 15 patients after
      multiple trauma with head injury (HTI-ISS 38 +/- 2 and Glasgow Coma Scale 4 +/-
      1). The urea production rate (UPR) could be significantly reduced by the
      intramuscular administration of 1.5 IU of rhGH/kg bodyweight (BW) per day (UPR
      day: 5, 62 +/- 6.7 gm/d vs. UPR day: 10, 42.6 +/- 5.9 gm/d). The catabolic index
      of Bistrian (BI) was significantly lower after rhGH therapy on day 10 compared to
      day 5. IGF-1 increased significantly after the administration of rhGH. The
      nitrogen balance, however, did not become positive, despite the administration of
      rhGH. The changes in sepsis were estimated by the scoring system according to
      Elebute and Stoner on days 3, 5, 7, 10, and 13. In those patients who were
      available for post-treatment evaluation the parameters had returned to baseline
      values after the withdrawal of rhGH. Results indicate that this therapy might
      ameliorate the nitrogen intake, but has no influence on the course of sepsis.
      Compared to previously published results in nonseptic patients, the somatomedin
      inhibitors as well as the split-products of the complement system and the
      metabolites of arachidonic acid may have been responsible for this weak effect of
      rhGH and IGF-1 in septicemia.

PMID- 1986139
TI  - Techniques of emergency ventilation: a model to evaluate tidal volume, airway
      pressure, and gastric insufflation.
AB  - We designed a model to evaluate the effectiveness of various noninvasive methods
      of ventilation. The upper airway was simulated with the head of a Resusci-Annie
      which was attached to a test lung. The esophagus and stomach were simulated with
      a Penrose drain connected to a rolling seal spirometer via a PEEP valve. Fifteen
      paramedic volunteers ventilated the model utilizing mouth-to-mouth, mouth-to
      mask, bag-valve-mask, or portable field ventilator (Impact or HARV). Recording of
      tidal volume, gastric volume, and proximal and distal airway pressure was
      completed at three different levels of compliance. At normal compliance, all
      methods except the HARV met or exceeded American Heart Association standards. As
      compliance decreased, tidal volume fell and gastric insufflation increased. At a
      compliance of 0.02 L/cm H2O all methods failed to meet AHA standards and gastric
      insufflation volume equalled delivered tidal volumes for mouth-to-mouth and mouth
      to-mask techniques. Mouth-to-mouth and mouth-to-mask techniques generated the
      largest tidal volumes but also created the largest volume of gastric
      insufflation. The Impact ventilator provided an acceptable tidal volume with
      minimal gastric insufflation. Our results suggest that mouth-to-mask ventilation
      with supplemental oxygen enrichment is the most efficient technique for non
      invasive airway management.

PMID- 1986140
TI  - Delayed union of fibular fractures accompanying fractures of the tibial shaft.
AB  - Among 440 adult patients with tibial shaft fracture and accompanying fibular
      fracture there were eight cases with radiographically ununited fibulae 4 months
      after the injury, each with uneventful tibial union. Fractures with severe soft
      tissue injuries were excluded from this study. In 293 patients the treatment
      method of the tibial fracture was conservative, comprising closed reduction and
      immobilization by long plaster cast. In 147 patients it was intramedullary
      Kuntscher nailing, and all the eight cases with delayed fibular union occurred
      among these, the frequency being 5.4%. The typical accompanying fibular fracture
      to develop delayed union was a comminuted one in the middle or distal third of
      the bone. At a followup examination 5 to 8 years after the original injury four
      of the eight fractures were found to have ultimately spontaneously united, while
      three showed a radiographically indisputable nonunion. One patient had undergone
      segmental fibular ostectomy because of persistent local pain but in the remaining
      patients the subjective symptoms were negligible. The occurrence of delayed
      fibular union in association with rigid intramedullary nailing of concomitant
      tibial shaft fracture is a phenomenon of which trauma surgeons should be aware
      even if the natural course of the condition often seems to be benign.

PMID- 1986141
TI  - Screening for lung cancer.

PMID- 1986142
TI  - Parathyroid autotransplantation during thyroid surgery.
AB  - Permanent hypoparathyroidism is one of the most distressing complications of
      thyroid surgery. The incidence of this iatrogenic complication varies between 3
      and 25 percent among patients undergoing total thyroidectomy. Parathyroid injury
      may be caused by inadvertent removal of the parathyroids, ligation of the blood
      supply, or destruction secondary to capsular hematoma. Attention to such
      technical details as identification of the parathyroids, dissection close to the
      thyroid gland, preservation of the blood supply to the parathyroids, and avoiding
      manipulation of parathyroids reduces the incidence of temporary and permanent
      hypoparathyrodism. However, if the parathyroids are injured, the best method of
      preserving their function is by autotransplantation. Over the past 7 years we
      have performed 250 thyroidectomies. An attempt was made to identify and preserve
      parathyroid gland in each case. Even during lobectomy procedures, the ipsilateral
      parathyroids were identified and preserved. Whenever any of the parathyroids was
      devascularized or separated from the surrounding structures, it was
      autotransplanted into the sternomastoid muscle. The sternomastoid was chosen for
      autotransplantation rather than forearm muscles to avoid an added incision and
      because selective measurement of parathormone is not essential in this group of
      patients. Prior to autotransplantation, confirmation of the nature of the tissue
      was made by frozen section of a small portion of the parathyroid gland.
      Parathyroid autotransplantation was performed in 15 instances, even when only one
      parathyroid was injured. Only one member of this group of 15 patients developed
      temporary hypoparathyroidism, which disappeared after 4 weeks of calcium
      supplementation. The remaining patients had an uncomplicated recovery.
      Autotransplantation of the parathyroid glands should be performed whenever the
      parathyroid is devascularized or damaged by retraction or hematoma. It is
      essential for every thyroid surgeon to be familiar with the technique of
      parathyroid autotransplantation.

PMID- 1986143
TI  - Modified anterior compartment resection.
AB  - In the majority of patients with soft tissue sarcomas of the anterior compartment
      of the thigh, it is possible to preserve a small portion of the quadriceps with
      intact nerve supply without compromising on the radicality of the procedure or
      the local control rate. The distal one-third of the vastus medialis can usually
      be spared with a long, slender branch providing its innervation. Dissection of
      the femoral nerve below the inguinal ligament and its branch(es) to an uninvolved
      area of the quadricepts the farthest from the location of the tumor is essential.
      This modified anterior compartment resection improves dramatically the function
      of the extremity.

PMID- 1986144
TI  - Two prostate carcinoma cell lines demonstrate abnormalities in tumor suppressor
      genes.
AB  - Two prostate carcinoma cell lines, DU-145 and PC-3, were examined for
      abnormalities in the retinoblastoma (Rb) and the p53 putative tumor suppressor
      genes. We found an abnormal Rb gene product in DU-145 using Western blot
      analysis. Polymerase chain reaction amplification followed by direct DNA
      sequencing demonstrated a base substitution mutation that generates a stop codon
      in exon 21. On Northern, Southern, and Western blot analysis, the p53 gene and
      its product appear to be normal in DU-145. PC-3, however, failed to demonstrate
      expression of either the p53 transcript on Northern blot analysis or the p53
      protein on Western blot analysis, while the Rb gene products appeared to be
      normal on both Northern and Western blot analysis. This work extends the
      correlation between abnormal expression of putative tumor suppressor genes and
      human malignancies.

PMID- 1986145
TI  - Leukocyte alkaline phosphatase score in patients with cerebrovascular disease and
      in patients with primary and metastatic brain tumors.
AB  - Leukocyte alkaline phosphatase (LAP) activity in peripheral blood was determined
      in 54 patients with cerebrovascular disease (CVD), 11 patients with primary brain
      tumor, and 23 patients with metastatic brain tumor. The LAP score of the primary
      brain tumor patients (155 +/- 40) was significantly higher (P less than 0.03)
      than the LAP score for cerebrovascular disease patients (96 +/- 87). The LAP
      score levels of the metastatic brain tumor patients (251 +/- 55) was
      significantly higher as compared with both the cerebrovascular disease (P less
      than 0.001) and primary brain tumor groups (P less than 0.001). The LAP score
      could serve as an additional, although non-specific, marker to assist in the
      differentiation between cerebrovascular disease and brain tumors.

PMID- 1986146
TI  - Implantation of tumor xenografts in nude mice: an improved methodology.
AB  - Xenografting of neoplasms is a common technique in cancer research. Implantation
      of non-uniform tumor tissue fragments often yields tumor nodules of irregular
      size and shape, which is disadvantageous. We therefore developed a device to
      standardize size and shape of such implants. This instrument is effective,
      inexpensive to fabricate, and simple to use.

PMID- 1986147
TI  - Dysgerminoma of the ovary: review of 27 cases.
AB  - Twenty-seven patients with pure dysgerminoma were seen at the Tata Memorial
      Hospital, Bombay, between January 1980 and December 1984. Of the 10 patients in
      stage I, 2 patients underwent a unilateral salpingoophorectomy (USO) and were
      kept under observation without any adjuvant therapy, while the remaining patients
      received adjuvant treatment following surgery. All of the 6 patients in stage II
      and 4 of 7 in stage III had total abdominal hysterectomy and bilateral salpingo
      oophorectomy (TAHBSO) followed by postoperative radiotherapy. One patient
      presented in stage IV and 3 patients presented with recurrence after previous
      definitive treatment undertaken at other institutions. The disease free, as well
      as the overall survival, at 108 months, for the 24 cases primarily treated at
      this institution, is 81% and 88% respectively, and, for patients in stages I and
      II, 100% (Kaplan-Meier estimation). The need for controlled clinical trials to
      devise optimal therapy in the early clinical stages and use of chemotherapy for
      advanced stages of this highly curable entity are stressed.

PMID- 1986148
TI  - Renal oncocytoma: long-term follow-up and flow cytometric DNA analysis.
AB  - We report a retrospective study on the clinicopathologic features and flow
      cytometric DNA analysis of ten renal oncocytomas compared with a control group of
      ten randomly selected renal cell carcinomas. Among the oncocytoma patients, no
      recurrences or metastases were noted over an average follow-up of 6.7 years
      (range = 6 months to 16 years). Reproducible, high-quality DNA histograms were
      obtained on the paraffin-embedded specimens by using our modified flow cytometric
      procedure. One aneuploid (10%) and two hyperdiploid tumors (20%) were found in
      the oncocytoma group. There was no correlation between these abnormal DNA
      histographic patterns and survival or tumor stages. On the contrary, a good
      correlation was found between tumor grades and DNA ploidy in the controls. We
      conclude that renal oncocytoma is a clinically benign tumor, yet it may exhibit
      varying degrees of flow cytometric DNA abnormalities, which have no predictive
      value on survival and probably reflect the characteristics of oncocytes rather
      than its malignant potential.

PMID- 1986149
TI  - Granular cell neoplasm of the extrahepatic biliary tree: morphological,
      ultrastructural, and immunohistochemical study and review of the literature.
AB  - A recent case of a biliary granular cell tumor of the cystic duct prompted a
      literature review and an extensive pathological examination of the tumor in
      question. A total of 44 cases have been described mostly in black females. Most
      cases present with biliary symptoms, and simple surgical resection allows
      complete control of this benign condition. Granular cell tumors are most likely
      derived from neural crest cells.

PMID- 1986150
TI  - Adjuvant, specific, active immunotherapy for resectable squamous cell lung
      carcinoma: a 5-year survival analysis.
AB  - In 1976 Stewart et al. (Annals of the New York Academy of Sciences 277:436-466)
      reported the effectiveness of adjuvant specific active immunotherapy of lung
      carcinoma in improving the postoperative survival of stage I lung carcinoma
      patients in a phase II study using lung carcinoma-associated antigen (TAA) and
      complete Freund's adjuvant (CFA). A phase III study was then designed by the
      authors to see the effects of specific active immunotherapy compared to the
      conventional management (no treatment) and to nonspecific immunotherapy. From
      1976 to 1981, 85 patients with resectable (stages I and II) squamous cell lung
      carcinoma were entered into a randomized study: 1) control group; 2) specific
      immunotherapy group--three monthly doses of 500 micrograms of TAA emulsified with
      CFA; 3) nonspecific immunotherapy group--three monthly doses of CFA emulsified in
      saline. All the patients in the study received skin tests with 100 micrograms of
      the same TAA used for the immunotherapy. Recently, a 5-year follow-up of all the
      patients became available: The life table 5-year survival of group 1 was 34%, of
      group 2 was 75%, and of group 3 was 53%. The median survivals for the three
      groups were group 1, 38 months; group 2, 106 months; and group 3, 71 months. The
      difference was significant at P = .007 (Cox-Mantel test).

PMID- 1986152
TI  - Role of dipyridamole-echocardiography test in the evaluation of coronary reserve
      after coronary artery bypass grafting.
AB  - The object of this study was to assess the usefulness of the dipyridamole
      echocardiography test in the early evaluation of coronary artery bypass grafting,
      when the use of an exercise stress test is precluded. We studied 39 consecutive
      patients (37 men and two women, mean age 57.3 years) referred to our institute
      for elective coronary artery bypass. Five patients had single, 12 patients
      double, 20 patients triple vessel disease, and two had left main stem disease.
      Nineteen left internal mammary artery grafts, 20 sequential grafts, and 39 single
      vein grafts were performed. All the patients were subjected to the test before
      (time range 1 to 3 days) and after (time range 6 to 10 days) the operation in the
      absence of therapy. Dipyridamole was administered intravenously 0.56 mg/kg over 4
      minutes (low dose); if no effect was apparent, an additional 0.28 mg/kg over 2
      minutes (high dose) was given. During the test, blood pressure and a twelve-lead
      electrocardiogram were monitored. An arbitrary wall motion score was derived by
      dividing the left ventricle into six regions and grading from 0 to 3
      normokinetic, hypokinetic, akinetic, and dyskinetic zones. Preoperatively the
      test was positive in 38 patients as evidenced by wall motion abnormalities (36
      patients had electrocardiographic changes) and in one patient by
      electrocardiographic changes and chest pain; 22 tests were positive after the low
      dose and 17 after the high dose. Angina was present in 33 patients. Mean wall
      motion score was 1.64 per patient in the basal condition and 4.03 per patient
      after the test (p less than 0.001). After coronary bypass in three patients the
      test was positive at the same dosage that was used preoperatively, as shown by
      wall motion abnormalities (in two patients by electrocardiographic changes, as
      well). Four patients had symptoms. Furthermore, at 6 months' follow-up, a
      treadmill stress test performed in these three patients was positive for ischemia
      and angina. The wall motion score was 1.25 per patient in the basal condition and
      1.53 per patient after the test (no significant difference). When the
      preoperative wall motion score obtained after dipyridamole echocardiography was
      compared with the postoperative score, a statistically significant difference was
      seen: 4.03 per patient versus 1.53 per patient (p less than 001). In eight
      patients we observed an improvement of basal myocardial contractility after the
      operation, which indicates the reversibility of wall motion abnormalities
      observed before coronary bypass. In conclusion our data show that the
      dipyridamole-echocardiography test is a suitable method for the early assessment
      of bypass grafting when other methods, exercise dependent, are not
      indicated.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1986151
TI  - Long-term follow-up comparing subclavian flap angioplasty to resection with
      modified oblique end-to-end anastomosis.
AB  - The definitive surgical procedure for correction of aortic coarctation remains
      controversial. Therefore, we retrospectively reviewed a total of 56 children
      under 4 years of age with coarctation repair between 1977 and 1986. Thirty-four
      had the subclavian flap angioplasty technique and 22 had resection with oblique
      end-to-end anastomosis. The group was further subdivided to include only the 23
      infants less than 3 months of age--eight infants with resection with oblique end
      to-end anastomosis (less than or equal to 3ETE) and 15 infants with subclavian
      flap angioplasty (greater than or equal to 3SFA). The remaining 33 patients older
      than 3 months of age were divided into 14 patients with resection and oblique end
      to-end anastomosis (greater than 3ETE) and 19 patients with the subclavian flap
      angioplasty technique (greater than 3SFA). The overall mortality was not
      significantly different between techniques. Postoperative hypertension was
      significantly more prevalent with end-to-end anastomosis than with the subclavian
      flap angioplasty technique (p less than 0.01). Seven patients had recurrent
      coarctation. The 6-year actuarial freedom from recoarctation was 93% +/- 6% in
      the less than or equal to 3SFA group compared with 53% +/- 20% in the less than
      or equal to 3ETE group (p less than 0.02), but there was no significant
      difference in those children operated on at a later age regarding the type of
      coarctation repair. Therefore, we recommend subclavian flap angioplasty in
      patients less than 3 months of age. In those older than 3 months either procedure
      is safe and the risk of recoarctation is similar.

PMID- 1986153
TI  - Does use of gastroepiploic artery graft increase surgical risk?
AB  - Seventy patients in whom the gastroepiploic artery was used for coronary artery
      bypass grafting were compared with 70 patients in whom the gastroepiploic artery
      was not used. Mean age was 56.8 years in the group in which this artery was used
      and 61.8 years in the group in which it was not (p less than 0.001). All other
      preoperative characteristics including number of women, extent of coronary artery
      disease, previous myocardial infarction, unstable angina, and preoperative left
      ventricular function were not significantly different between the two groups. An
      internal mammary artery graft was concomitantly used in 68 patients (97%) of the
      group with a gastroepiploic artery graft and in 61 patients (87%) without such a
      graft. The mean number of distal anastomoses was 3.3 and 3.4, aortic crossclamp
      time was 65.3 +/- 19.9 minutes and 54.0 +/- 20.1 minutes, and cardiopulmonary
      bypass time was 114.8 +/- 23.6 minutes and 112.9 +/- 25.0 minutes, respectively,
      in the groups with and without a gastroepiploic artery graft. Only aortic
      crossclamp time was significantly (p less than 0.05) longer in the group with a
      gastroepiploic artery graft. There were two (2.9%) early deaths and two (2.9%)
      new Q-wave infarctions in both groups. Intraaortic balloon pumping was required
      in five patients (7.1%) in the group with a gastroepiploic artery graft and in
      three patients (4.3%) without this graft. Postoperative complications were
      similar and rare in both groups. Intraoperative endoscopic laser Doppler study
      demonstrated no significant change of gastric mucosal blood flow before and after
      division of the gastroepiploic artery. We concluded that there is no additional
      risk in the use of the gastroepiploic artery for coronary bypass grafting, and a
      favorable outcome can be expected.

PMID- 1986154
TI  - Neonatal repair of tetralogy of Fallot with and without pulmonary atresia.
AB  - Our experience with the arterial switch operation for transposition of the great
      arteries has confirmed the attainability of excellent results with elective
      neonatal surgery. Up to this time, we have repaired tetralogy of Fallot during
      the neonatal period only when symptoms, either severe persistent cyanosis or
      cyanotic spells, have been present. This review assesses the results of such
      nonelective neonatal correction of tetralogy between 1973 and 1988. Twenty-seven
      neonates with either symptomatic tetralogy of Fallot or symptomatic tetralogy of
      Fallot with valvar pulmonary atresia underwent repair. Mean age at repair was 8
      +/- 8.4 days and mean weight was 3.0 +/- 0.7 kg. Unsatisfactory palliative shunts
      had previously been placed elsewhere in four patients. Twenty-five transannular
      patches and two conduits were used for reconstruction of the right ventricular
      outflow tract. There were five deaths in the hospital, three of which were due to
      avoidable technical problems. All deaths occurred in patients with pulmonary
      artery (Nakata) index less than 150 mm2/m2. One premature child weighing 2.3 kg
      displayed an absent pulmonary valve-like syndrome after repair and died late of
      respiratory complications caused by aneurysmal branch pulmonary arteries.
      Actuarial survival at 5 years was 74%. There was a single rapidly declining
      hazard phase for death, with the hazard approaching zero at 1 1/2 years after
      repair. Actuarial freedom from need for reoperation was 76% at 5 years.
      Postoperative catheterization of 15 long-term survivors showed right ventricular
      pressure less than 70% systemic in 13 cases. All patients are symptomatically
      well and functioning in sinus rhythm 1 to 15 years after repair (mean, 5 +/- 4
      years). This experience with neonates with symptoms suggests that, if mortality
      is lower in the absence of symptoms, elective repair of tetralogy of Fallot could
      be reasonably undertaken during the first months of life.

PMID- 1986155
TI  - Atrioventricular septal defects. Analysis of short- and medium-term results.
AB  - Atrioventricular septal defects were repaired in 87 patients from 1981 to 1988.
      Interventricular communications were present in 73 patients, and major associated
      anomalies were present in 17 (tetralogy of Fallot in four, double-outlet right
      ventricle in two, multiple ventricular septal defects in 11). Five deaths
      occurred in the hospital (5.7%; 70% confidence limits, 3.2% to 9.7%). A
      preoperative New York Heart Association class V functional condition was the only
      incremental risk factor (p = 0.02) for death in the hospital. No patient (0%; 70%
      confidence limits, 0% to 2.15%) had complete heart block. Actuarial survival rate
      at 80 months was 81.4%. The only incremental risk factor (p = 0.005) leading to
      reoperation was a preoperative valve incompetence. Actuarial rate at 80 months
      for freedom from reoperation was 84.2% in the overall group of patients after
      repair of atrioventricular septal defect. We conclude that an improvement in
      survival and success rates should be found when a policy of earlier repair is
      followed.

PMID- 1986156
TI  - Studies of myocardial protection in the immature heart. III. Models of ischemic
      and hypoxic/ischemic injury in the immature puppy heart.
AB  - This study compares the metabolic and functional effects of three different
      models of ischemia in the immature heart. The intent was (1) to develop a model
      of energy-depleted and functionally depressed heart to be used in subsequent
      studies of myocardial protection and (2) to characterize the biochemical changes
      following different interventions. Forty-five minutes of normothermic global
      ischemia produced severe depletion of adenosine triphosphate and creatine
      phosphate (greater than 70%) but was associated with 85% +/- 10% recovery of left
      ventricular function. Postischemic functional depression (less than 30% recovery)
      could be produced by either (1) extending the ischemic duration to 60 minutes or
      (2) preceding 45 minutes of ischemia by 60 minutes of hypoxic stress (oxygen
      tension 25 to 30 mm Hg). Neither of these more severe interventions caused more
      profound depletion of adenosine triphosphate or creatine phosphate, but hypoxic
      stress produced marked tissue depletion of glutamate (52%) and aspartate (48%)
      before aortic clamping. Longer ischemia or preceding hypoxia led to greater
      myocardial accumulation of lactate (greater than 250 versus 104 mumol/gm dry
      weight) and succinate (18 versus 11 mumol/gm dry weight) during aortic clamping,
      p less than 0.05 versus 45 minutes of ischemia) and greater postischemic
      depression and amino acid (greater than 65% aspartate depletion) and carbohydrate
      (greater than 50% glycogen depletion) metabolism, p less than 0.05 versus simple
      ischemia. These findings suggest that more severe ischemic/hypoxic models are
      needed in immature hearts to produce functional depression, and the biochemical
      analyses suggest the characteristics of metabolic defects that must be corrected
      to resuscitate these hearts during surgical correction of congenital defects.

PMID- 1986157
TI  - Bedside assessment of phrenic nerve function in infants and children.
AB  - Phrenic nerve damage is widely recognized after cardiac operations and is
      associated with an increased morbidity and mortality. Retrospective studies in
      children have estimated a prevalence of phrenic damage of between 0.5% and 2.2%,
      but all these studies have limited their investigations to patients who have
      clinical problems postoperatively, and they have all used clinical or radiologic
      methods to diagnose the damage. These methods are indirect and hard to evaluate,
      making the accurate early diagnosis of phrenic nerve damage very difficult.
      Measurement of phrenic nerve conduction time (phrenic latency) allows direct
      evaluation of phrenic function and integrity, making it potentially much more
      specific than indirect methods. Using a simplified method of direct phrenic nerve
      stimulation, we have developed a method of measuring phrenic latency at the
      bedside in infants and children. A 1 Hz electrical stimulus is applied over the
      phrenic nerve in the neck and a diaphragmatic electromyogram from the seventh and
      eighth intercostal spaces is displayed on a storage oscilloscope. Phrenic latency
      can be measured directly from the screen. Using these methods we have now studied
      37 children (aged 2 days to 15 years) before and after cardiac operations. Mean
      phrenic latency was 5.4 +/- 1.0 msec on the right and 5.4 +/- 1.0 msec on the
      left. Prolongation of phrenic latency by more than 2 msec was found in seven of
      66 postoperative measurements (10.6%). These patients had a substantially worse
      postoperative course. We believe this technique to be an important contribution
      to the diagnosis of postoperative phrenic nerve damage, and one that can help in
      clinical practice to elucidate an important cause of postoperative morbidity and
      mortality.

PMID- 1986158
TI  - Prostaglandin F1 alpha levels during and after neonatal extracorporeal membrane
      oxygenation.
AB  - Infants receiving extracorporeal membrane oxygenation therapy undergo long-term
      cardiopulmonary bypass, are systemically heparinized, and frequently receive
      platelet transfusions. Prostacyclin is a powerful inhibitor of platelet
      aggregation as well as a potent vasodilator. The levels of its stable metabolite
      prostaglandin F1 alpha increase significantly in children undergoing
      cardiopulmonary bypass during heart operations but decrease to preoperative
      levels after bypass. To determine the effect of long-term bypass on prostacyclin
      levels, multiple plasma samples were analyzed in 10 human neonates both during
      extracorporeal membrane oxygenation therapy and within 24 hours after
      extracorporeal membrane oxygenation. Prostaglandin F1 alpha, the stable
      metabolite of prostacyclin, was quantitated by radioimmunoassay in picograms per
      milliliter. Prostaglandin F1 alpha levels were elevated while the patients
      received extracorporeal membrane oxygenation therapy but decreased with duration
      of extracorporeal membrane oxygenation. In most infants, prostaglandin F1 alpha
      levels rose again during weaning from extracorporeal membrane oxygenation and
      remained elevated for 24 hours after extracorporeal membrane oxygenation.
      Extracorporeal membrane oxygenation course influenced circulating prostaglandin
      F1 alpha levels. Fluctuating prostaglandin F1 alpha levels are of clinical
      significance in the management of vasomotor tone and platelet function, common
      problems in the care and the prevention of hemorrhage in these critically ill
      infants.

PMID- 1986159
TI  - A reevaluation of heparin requirements for cardiopulmonary bypass.
AB  - We wished to determine if reduction in the standard heparin administration for
      cardiopulmonary bypass could be accomplished safely with the use of membrane
      oxygenators. An experimental study was designed to evaluate two different heparin
      administration protocols for cardiopulmonary bypass with hollow-fiber membrane
      oxygenators. Two groups of six pigs were submitted to hypothermic cardiopulmonary
      bypass (28 degrees C) for 3 hours, then rewarmed, decannulated, and reassessed
      after 1 hour. In group I (control) heparin was administered to maintain the
      activated clotting time in excess of 450 seconds; in group II activated clotting
      time was maintained between 250 and 300 seconds. The mean total heparin
      administered was 41,000 units in group I and 25,000 units in group II.
      Concentration of coagulation factors II, V, and VIII, fibrinogen, and platelet
      count were determined before, during, and 1 hour after bypass. No significant
      difference in any of these coagulation parameters was observed between the
      groups. The performance of the oxygenators was similar in both groups, with no
      evidence of thrombosis. Thus reduced heparin administration, enough to keep
      activated clotting time between 250 and 300 seconds, was not related either to
      major coagulation factors and platelet consumption or to derangements in the
      oxygenator's performance.

PMID- 1986161
TI  - Invited letter concerning: repair of coarctation of the aorta. Which operation?

PMID- 1986160
TI  - Fatal fungal pericarditis after cardiac surgery and immunosuppression.
AB  - The cases of two patients with fulminant pericarditis after cardiac surgery are
      reported. Both fungal infections developed after rethoracotomy for open-chest
      cardiac resuscitation and high-dose glucocorticoid treatment. Although the time
      course of both infections from the inoculation of fungi during rethoracotomy and
      immunosuppression with glucocorticoids to the lethal outcome was strikingly
      similar, histopathologic studies disclosed the disparate character of the two
      fungal pathogens responsible: the yeast Candida albicans and the angiotropic mold
      Aspergillus fumigatus.

PMID- 1986162
TI  - Surgical treatment of coarctation.

PMID- 1986163
TI  - Cardioplegia in neonatal heart.

PMID- 1986164
TI  - Retraining of the left ventricle with a left ventricular assist device (Bio
      Medicus) after the arterial switch operation.

PMID- 1986165
TI  - Invited letter concerning: bleeding time test.

PMID- 1986166
TI  - Predictive value of the bleeding time in coronary artery bypass grafting.

PMID- 1986167
TI  - Studies of myocardial protection in the immature heart. IV. Improved tolerance of
      immature myocardium to hypoxia and ischemia by intravenous metabolic support.
AB  - Thirteen immature puppies (2 to 4 kg) underwent 1 hour of acute hypoxia (oxygen
      tension 25 to 30 mm Hg), followed by 45 minutes of normothermic global ischemia
      on total vented bypass with normal blood reperfusion. Ventricular function was
      assessed by inscribing Starling function curves and measuring stroke work indices
      before hypoxia and after reperfusion. Seven puppies (control) received normal
      saline infusion at 4 ml/kg/hr. Six other puppies received a 4 ml/kg/hr
      intravenous infusion of glutamate/aspartate, glucose-insulin-potassium,
      mercaptopropionyl glycine, carnitine, and catalase during hypoxia and
      reperfusion. In control hearts, acute hypoxia depleted myocardial glutamate and
      aspartate by 52% (p less than 0.05 versus prehypoxia) and 48% (p less than 0.05
      versus prehypoxia) and caused severe hemodynamic deterioration (55% decrease of
      stroke work index) (p less than 0.05 versus prehypoxia); three of seven (43%)
      required premature institution of bypass. Postischemic left ventricular function
      recovered to only 40% of control levels (p less than 0.05 versus prehypoxia). In
      contrast, intravenous metabolic infusions maintained tissue glutamate (p less
      than 0.05 versus control group) and aspartate (p less than 0.05 versus control
      group) in treated hearts during hypoxia and allowed cardiac index to rise 20% (p
      less than 0.05 versus prehypoxia); all treated hearts tolerated 1 hour of
      hypoxia, and stroke work recovered 70% (p less than 0.05 versus control group) of
      stroke work index after subsequent ischemia. Impaired tolerance of immature
      hearts to acute hypoxia and subsequent ischemia is due to substrate depletion.
      This impairment can be reduced by intravenous metabolic support during hypoxia
      and reperfusion and leads to improved recovery of postischemic function.

PMID- 1986168
TI  - Studies of myocardial protection in the immature heart. V. Safety of prolonged
      aortic clamping with hypocalcemic glutamate/aspartate blood cardioplegia.
AB  - This study tests the hypothesis that multidose, hypocalcemic aspartate/glutamate
      enriched blood cardioplegia provides safe and effective protection during
      prolonged aortic clamping of immature hearts. Of 17 puppies (6 to 8 weeks of age,
      3 to 5 kg) placed on vented cardiopulmonary bypass, five were subjected to 60
      minutes of 37 degrees C global ischemia without cardioplegic protection and seven
      underwent 120 minutes of aortic clamping with 4 degrees C multidose
      aspartate/glutamate-enriched blood cardioplegia ([Ca++] = 0.2 mmol/L), preceded
      and followed by 37 degrees C blood cardioplegic induction and reperfusion. Five
      puppies underwent blood cardioplegic perfusion for 10 minutes without intervening
      ischemia to assess the effect of the cardioplegic solution and the delivery
      techniques. Left ventricular performance was assessed 30 minutes after bypass was
      discontinued (Starling function curves). Hearts were studied for high-energy
      phosphates and tissue amino acids. One hour of normothermic ischemia resulted in
      profound functional depression, with peak stroke work index only 43% of control
      (0.7 +/- 0.1 versus 1.7 +/- 0.2 gm x m/kg, p less than 0.05). There was 70%
      depletion of adenosine triphosphate (7.6 +/- 1 versus control 20.3 +/- 1 mumol/gm
      dry weight, p less than 0.05) and 75% glutamate loss (6.6 +/- 1 versus control
      26.4 +/- 3 mumol/gm, p less than 0.05). In contrast, after 2 hours of aortic
      clamping with multidose blood cardioplegia preceded and followed by 37 degrees C
      blood cardioplegia, there was complete recovery of left ventricular function
      (peak stroke work index 1.6 +/- 0.2 gm x m/kg) and maintenance of adenosine
      triphosphates, glutamate, and aspartate levels at or above control levels
      adenosine triphosphate 18 +/- 2 mumol/gm, aspartate 21 +/- 1 versus control 2
      mumol/gm, and glutamate 25.4 +/- 2 mumol/gm). Puppy hearts receiving blood
      cardioplegic perfusion without ischemia had complete recovery of control stroke
      work index. We conclude that methods of myocardial protection used in adults,
      with amino acid-enriched, reduced-calcium blood cardioplegia, can be applied
      safely to the neonatal heart and allow for complete functional and metabolic
      recovery after prolonged aortic clamping.

PMID- 1986169
TI  - Factors predictive of results of direct ablative operations for drug-refractory
      ventricular tachycardia. Analysis of 80 patients.
AB  - During a 9-year period 80 patients with drug-resistant sustained ventricular
      tachycardia underwent direct surgical ablation of arrhythmogenic myocardium.
      Sixty-nine were male (86%) and 11 female (14%), with 1.9 +/- 1.1 (standard
      deviation) ventricular tachycardia morphologies per patient. The mean number of
      drugs failed was 3.7 +/- 1.6 per patient. The preoperative left ventricular
      ejection fraction was 36.4% +/- 14.4%. Complete preoperative endocardial mapping
      data (greater than 4 endocardial sites in each ventricular tachycardia) were
      available for 60 of the 80 patients (75%) and intraoperative endocardial data in
      the clinical ventricular tachycardia was obtained in 37 (46.3%) of the patients.
      In 17 patients mapped intraoperatively by computer-assisted techniques, complete
      epicardial and endocardial data in the clinical ventricular tachycardia were
      obtained in 14 patients (82.4%). Overall, 73 of 80 (91.3%) had some mapping data
      available. Hospital mortality occurred in 10 patients (12.5%) at a mean interval
      of 13.5 days, range 0 to 62 days. Postoperatively the clinical ventricular
      tachycardia has not recurred in 65 of 70 surviving patients (92.9%). Nonclinical
      ventricular tachycardia occurred in another four patients. All nine patients with
      postoperative ventricular tachycardia responded to drugs. The major factors
      predictive of hospital mortality were prolonged cardiopulmonary bypass (greater
      than 150 minutes), preoperative ejection fraction less than 31%, and incomplete
      preoperative mapping. Hospital mortality in patients with an ejection fraction
      below 31% was significantly associated with a history of amiodarone usage. At 3
      years of follow-up, freedom from sudden cardiac death was 95.7%, and 86.7% of
      patients were free of ventricular tachycardia on no antiarrhythmic drugs. These
      results suggest that direct ventricular tachycardia operations are an effective
      form of therapy for patients with sustained monomorphic ventricular tachycardia.

PMID- 1986171
TI  - Surgical interruption of postganglionic innervation of the sinoatrial nodal
      region.
AB  - Recent experiments have revealed synapses that selectively mediate right and left
      vagal regulation of sinoatrial function in the fat pad overlying and surrounding
      the right pulmonary vein complex. However, precise vagal postganglionic pathways
      to the sinoatrial region have remained obscure. Such pathways, including
      critically important neural inputs to sinoatrial and atrioventricular nodal
      regions, may be vulnerable to surgical approaches to atrial or intracardiac
      repair. The present experiments seek to delineate specific autonomic pathways to
      the sinoatrial region of the canine heart. The distal ends of the cut right and
      left cervical vagi and the right and left ansae subclaviae were electrically
      stimulated (10 to 20 Hz, 1 msec, 2 to 3 V) before and after surgical incisions
      were placed. Cut No. 1 was made longitudinally along the ventral caval surface
      from the pericardial reflection caudally to the pulmonary vein fat pad, cut No. 2
      was made from the caudal end of cut No. 1 transversely across the sulcus
      terminalis to a point midway across the anterior (ventral) surface of the right
      atrium. Each incision was closed with 4-0 silk, with care being taken to avoid
      injury to either the sinoatrial nodal or the pulmonary fat pad regions. In four
      of seven animals, these two incisions totally interrupted vagal input to the
      sinoatrial node, whereas in the remaining three dogs a residual inhibitory
      influence remained. These residual fibers were surgically ablated by excision of
      globular fat pads situated on the rostrodorsal surfaces of the right superior
      pulmonary vein, suggesting a dorsorostral route into the interatrial septum and
      thence to the sinoatrial node. There was little or no interruption of either
      right or left vagal input to the atrioventricular nodal region; sympathetic
      supplies to both sinoatrial nodal and atrioventricular nodal regions remained
      essentially intact after the two incisions. Thus the major parasympathetic
      postganglionic projections to the sinoatrial node in the dog heart are by way of
      the free wall of the right atrium and are vulnerable to surgical interventions in
      this portion of the heart.

PMID- 1986170
TI  - Influence of clinical and hemodynamic variables on risk of supraventricular
      tachycardia after coronary artery bypass.
AB  - The influence of 45 variables on risk of postoperative supraventricular
      tachycardia was evaluated by univariate and multivariate analysis of data from
      800 consecutive patients who underwent isolated coronary artery bypass during a 6
      year interval. Postoperative supraventricular arrhythmias occurred in 186
      patients (23%) but did not contribute to any of the six early deaths (30-day
      mortality rate, 0.8%). Mean (+/- standard deviation) length of hospital stay was
      longer (9.8 +/- 5.7 versus 8.3 +/- 3.5 days; p less than 0.0001) and mean age was
      older (65 versus 60 years; p less than 0.002) in patients with postoperative
      supraventricular tachycardia than in those with regular rhythm. Risk of
      supraventricular tachycardia was increased in patients with a history of atrial
      arrhythmias (45% versus 22%; p less than 0.002) or premature atrial contractions
      on the preoperative electrocardiogram (48% versus 22%; p less than 0.002).
      Multiple logistic regression analysis identified age 65 years or more, history of
      atrial arrhythmia or preoperative premature atrial contractions, and preoperative
      left ventricular end-diastolic pressure 20 mm Hg or more as independent
      predictors of postoperative supraventricular tachycardia. Six percent of patients
      converted to sinus rhythm spontaneously; 82% of patients converted within 1.1 +/-
      1.9 days after onset of supraventricular tachycardia on treatment with digoxin or
      beta-adrenergic blocking drugs or both. Only 10% of patients with
      supraventricular tachycardia required electrical cardioversion. We conclude that
      the risk of supraventricular tachycardia after coronary artery bypass is
      influenced by patient-related variables and is effectively managed by
      conventional therapy. Prophylactic treatment should be reserved for elderly
      patients, especially those who have atrial arrhythmias or have preoperative left
      ventricular end-diastolic pressure 20 mm Hg or more.

PMID- 1986173
TI  - Long-term clinical results with the Ionescu-Shiley pericardial xenograft.
AB  - From 1977 to 1987, 829 Ionescu-Shiley pericardial valves (Shiley, Inc., Irvine,
      Calif.) were implanted in 766 patients at the University of Ottawa Heart
      Institute. There were 476 patients who had aortic valve replacement, 234 who had
      mitral valve replacement, and 44 who had double valve replacement. The standard
      profile design was used in 508 patients and the low-profile design in 321
      patients. Follow-up was obtained for 97% of patients, with calculation of event
      free probabilities. At 10 years the overall probability of freedom from
      structural failure was 48% +/- 7% after aortic valve replacement, 44% +/- 15%
      after mitral valve replacement, and 79% +/- 11% after double valve replacement.
      Although at 5 years the probability of failure was statistically lower with the
      low-profile design, this favorability was lost by 6 years. Freedom from
      structural failure was only 47% +/- 7% for the standard-profile valve at 10
      years. Thus the probability of freedom from reoperation was only 46% +/- 7% after
      aortic valve replacement, 39% +/- 6% after mitral valve replacement, and 65% +/-
      20% after double valve replacement at 10 years. Thromboembolism occurred in 69
      patients, for a predicted freedom from this complication at 10 years of 79% +/-
      3% after aortic, 73% +/- 7% after mitral, and 96% +/- 4% after double valve
      replacement. There were 31 cases of endocarditis. The 10-year predicted freedom
      from endocarditis, therefore, was 86% +/- 3% after aortic, 98% +/- 1% after
      mitral, and 97% +/- 1% after double valve replacement. A total of 221 operative
      and late deaths were recorded in this series. Prosthetic valve failure accounted
      for 27% of late deaths. The 10-year survival rates were estimated to be 56% +/-
      5% (aortic valve replacement), 54% +/- 6% (mitral valve replacement), and 51% +/-
      8% (double valve replacement). We concluded that the Ionescu-Shiley pericardial
      xenograft provides less than optimal clinical performance and its use has been
      discontinued.

PMID- 1986172
TI  - The pericardial valve in the aortic position ten years later.
AB  - To assess the behavior of the pericardial valve at 10 years after implantation,
      the cases of 240 patients who had undergone aortic valve replacement with the
      standard Ionescu-Shiley (Shiley, Inc., Irvine, Calif.) bovine pericardial valve
      between February 1977 and December 1983 were reassessed. Follow-up of the 224
      hospital survivors was 99.6% complete. Fifty-seven valve-related events occurred.
      Fourteen were thrombotic events (1.2%/patient-year), 28 were intrinsic tissue
      failures (2.4%/patient-year), 13 were cases of prosthetic valve endocarditis
      (1.1%/patient-year), and 2 were paravalvular leaks (0.17%/patient-year). The
      linearized rate for death, reoperation, or both resulting from valve-related
      events was 3.6%/patient-year. Time-related hazard function for the instantaneous
      risk of death and/or reoperation resulting from valve-related events demonstrated
      an exponential increase after 80 months. These data, in conjunction with our
      previous reports on the histologic changes in pericardial collagen and the
      incidence of calcification (26/28), should be considered regarding new and future
      generations of pericardial bioprostheses. Although this device provides good
      hemodynamics and carries a low incidence of thromboembolism, it has a limited
      durability. New generations of pericardial valves may have improved structural
      features, but the behavior of glutaraldehyde-fixed, formaldehyde-stored bovine
      pericardium as currently selected and prepared is unlikely to change.

PMID- 1986174
TI  - Analysis of the Medtronic Intact bioprosthetic valve. Effects of "zero-pressure"
      fixation.
AB  - The long-term performance of current-design porcine xenograft valves has not been
      satisfactory. These valves are generally fixed at "low pressures" of about 3 to 5
      mm Hg. The Medtronic Intact (Medtronic, Inc., Minneapolis, Minn.) valve is fixed
      at "zero pressure" and is proposed as a better alternative to existing xenograft
      valves. A mechanical analysis of this valve has been carried out to determine if
      the Intact valve differs significantly from the low-pressure fixed xenograft.
      Twelve circumferential strips of tissue 5 mm wide were cut from the leaflets of
      four clinical-grade Intact valves. Their stress/strain, stress relaxation, and
      flexural behavior were examined mechanically and histologically. The Intact valve
      was more extensible than the low-pressure fixed xenograft (22% versus 12% strain,
      p less than 0.001), relaxed faster (p less than 0.001), and was more pliable than
      the xenograft (p less than 0.05). It did not, however, buckle less than did the
      low-pressure fixed xenograft during enforced bending, and it buckled
      significantly more than did fresh porcine aortic valve tissue (p less than
      0.001). The Intact valve also relaxed significantly more slowly than did the
      fresh tissue (p less than 0.05). Its bending stiffness had a stronger dependence
      on leaflet thickness than the bending thickness of fresh tissue had (p less than
      0.001) but a weaker dependence than the bending thickness of the low-pressure
      fixed xenograft material had (p less than 0.001). The Intact valve demonstrated a
      very large variability in extensibility, bending stiffness, and buckling
      behavior, with little correlation between these parameters. Some valves appeared
      to have wrinkled leaflets; others were likely fixed at different pressures. The
      shrinkage of the leaflet material at these low fixation pressures is likely
      important, since it can modify the elastic behavior of the valve cusps. Overall,
      the Intact valve had a more "natural" elastic behavior than had low-pressure
      fixed xenograft, and it should therefore experience lower stresses during normal
      valve function. It can be concluded that zero-pressure fixation does preserve
      many of the desirable stress-reducing properties of aortic valve tissue.

PMID- 1986175
TI  - Improving the effectiveness of screening for colorectal cancer by involving nurse
      clinicians.

PMID- 1986176
TI  - Estimating the treatment costs of breast and lung cancer.
AB  - The Continuous Medicare History Sample File (CMHSF) was used to derive an
      estimate of the lifetime direct medical expenses attributable to two chronic
      diseases, lung cancer and female breast cancer. These two cancers are the leading
      cancer causes of death in men and women in the United States. They inflict large
      costs on the population, both direct and indirect, but the costs have been
      difficult to measure. The primary obstacle to quantification is the intermittent
      and long-term nature of treatment for these diseases. A complete record of
      expenses cannot usually be obtained from one source, however, a review of all the
      national health surveys, as well as the Medicare statistical files identified the
      CMHSF, which is maintained by the Health Care Financing Administration in a
      format suitable for calculation of cumulative medical expenses. Some of the
      pertinent features of the CMHSF include the following: 1) it is a nationally
      representative sample of the Medicare population, 2) it is longitudinal covering
      an 8-year period from 1974 to 1981, 3) it captures the majority of medical
      expenses for each enrollee, and 4) it can be linked to other national data bases
      such as the National Death Index. Charges for three phases of cancer treatment
      were derived from the file: initial therapy, maintenance care, and terminal care.
      A method is described for computing the present value of life-time treatment
      costs from the phase-specific charges. The lifetime cost of treating breast
      cancer in 1984 dollars is $36,926 and lung cancer is $12,510.

PMID- 1986177
TI  - The impact of patient management guidelines on the care of breast, colorectal,
      and ovarian cancer patients in Italy.
AB  - The impact of a national education program based on the dissemination of written
      guidelines for the treatment of breast, colorectal, and ovarian cancer was
      investigated in Italy. Through a survey of 770 physicians exploring their
      knowledge and attitudes and a review of medical records of 1,483 patients
      assessing current clinical practice, this study examined whether 1) the
      guidelines reached the target population of physicians, 2) they were effective in
      shaping doctors' opinions, and 3) care patterns conformed with the guidelines.
      Overall, the net effect of the intervention appeared to be limited in terms of
      actual diffusion, attributable influence, and impact. As for diffusion, only 60%,
      47%, and 44% of doctors were aware of breast, colorectal, and ovarian cancer
      guidelines, respectively. Although doctors who were aware of the guidelines had
      more appropriate opinions than those who were not, overall agreement with
      recommendations was often unsatisfactory. With reference to guidelines
      recommendations, quality of care was far from optimal, especially in relation to
      diagnosis and staging. Marked variations in compliance with recommendations
      emerged with values ranging from 37% to 89%, from 48% to 82%, and from 10% to 97%
      for breast, colorectal, and ovarian cancer, respectively, and this held true even
      in hospitals where the larger awareness of the guidelines might have been
      expected to result in better quality care. It was concluded that any thorough
      assessment of the impact of educational interventions should include a careful
      analysis of the strategy and process of dissemination. The availability of
      clinically relevant messages must also be realistically considered before
      deciding whether the "guidelines approach" is the strategy most likely to
      succeed.

PMID- 1986178
TI  - Determinants of health insurance status among young adults.
AB  - This study evaluates the determinants of insurance coverage in the 18-24-year-old
      population using the National Medical Care Utilization and Expenditure Survey.
      Three specific issues are addressed: 1) the characteristics of the insured versus
      uninsured, 2) the reason given by the uninsured for not having coverage, and 3)
      the role of employment status and other variables in determining insurance
      status. An important consideration is whether age or usual activity is more
      important in its effect on insurance status. The results show that employment is
      the strongest predictor of insurance status in all age and usual activity
      subgroups. Generally, permanent/full-time workers are most likely to be insured.
      An exception to this trend is found for those attending school who are also
      permanent/part-time workers. These individuals are more likely to be insured than
      permanent full-time workers who are in school. Furthermore, young adults with
      lower incomes, less education, rural residence, not married, hispanic ethnicity,
      and Western geography are the least likely to be insured. The findings of this
      analysis can be used by policymakers to identify the mechanisms that can best
      enhance insurance coverage among young adults.

PMID- 1986179
TI  - Impact of a mandatory Medicaid case management program on prenatal care and birth
      outcomes. A retrospective analysis.
AB  - This study examined the impact of Philadelphia's mandatory Medicaid case
      management program (HealthPASS) on adequacy of prenatal care and birth outcomes
      among enrollees. A sample of 217 deliveries for HealthPASS patients at the
      Hospital of the University of Pennsylvania (HUP) during 1988 was compared with a
      matched sample of 1988 deliveries at HUP for whom the payor was Pennsylvania's
      traditional fee-for-service Medicaid program. Inpatient charts for all 434
      subjects were abstracted for information on sociodemographic characteristics,
      substance use during pregnancy (cigarettes, alcohol, and drugs), course and
      extent of prenatal care, and birth outcomes including birth weight, gestational
      age, and mortality. No significant differences were detected between HealthPASS
      and Medicaid groups, suggesting that the mandatory managed care program neither
      improved nor impeded access to needed services. These results were not surprising
      in view of the fact that HealthPASS actually did little to change provider or
      patient behavior with respect to obstetrical care. Both the HealthPASS and
      Medicaid groups experienced low rates of adequate prenatal care (39%) and high
      rates of low birth weight (20%). Also disturbing was the finding that at least
      46% of women smoked during pregnancy, at least 20% drank alcohol, and at least
      17% used cocaine. These findings support the need for continued efforts to
      improve both access to, and content of, prenatal care for the urban poor.

PMID- 1986180
TI  - Quality of acute episodic care in investor-owned ambulatory health centers.
AB  - This article examines the quality of acute episodic care for five diagnostic
      categories amenable to one-visit diagnosis and treatment at the nation's largest
      chain of investor-owned ambulatory care centers. A total of 803 medical records
      were audited for five common conditions and measured against specific protocols.
      In four of the five diagnostic categories studied--pharyngitis, otitis media,
      vaginitis, and use of tetanus immunization--42-97% of patients received care that
      met or exceeded the standards set by a panel of practicing academic physicians.
      In follow-up of an incidental high blood pressure reading, however, study
      physicians met the standard only 24% of the time. Some overprescribing and
      overtreatment with immunizations were detected. As far as comparison is possible
      to other studies, results suggest that care in this setting falls within the
      range of experience that has been reported for other types of practices. In spite
      of direct economic incentives to increase volume, little evidence was found of
      overuse of ancillary tests or unnecessary scheduling of repeat visits.

PMID- 1986181
TI  - Maternal and paternal alcohol use: effects on the immune system of the offspring.
AB  - There is no single mechanism which can account for such a complex biological
      phenomenon as immune regulation, nor is it clear how alcohol teratogenicity
      exerts its multiple adversive effects, including lasting immune deficits. Much of
      the research aimed at unravelling effects of pre- or early postnatal alcohol
      exposure on the organism's defense mechanisms and long-term health risks has been
      phenomenological. A better understanding of mechanisms which underlie alcohol
      effects on immune competency will require integrated studies of the neuro-immune
      endocrine networks.

PMID- 1986182
TI  - N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) does not modify the
      angiotensin II-stimulated calcium signal in cultured bovine glomerulosa cells.
AB  - Studies were performed to determine if the sustained elevation in [Ca2+]c noted
      previously in glomerulosa cells in response to Ang II resulted from the presence
      of HEPES in the experimental medium. At confluence, primary cultures of bovine
      glomerulosa cells were maintained for 24-30 h in the presence of either 14 mM
      NaHCO3/5% CO2 or 25 mM HEPES/4 mM NaHCO3/air. During subsequent experimental
      periods, cells were incubated in the presence of the corresponding or reciprocal
      buffer, and the effects of Ang II on [Ca2+]c were monitored by fura 2
      fluorescence. Increases in [Ca2+]c produced by Ang II in cells continuously
      maintained in either HCO3(-) - or HEPES-buffered media were similar, and with the
      same monolayer the nature of the Ang II-stimulated Ca2+ signal was independent of
      the buffer employed. Moreover, the Ang II-stimulated Ca2+ signal was not
      significantly affected by the removal of HCO3- from the superfusate. These
      results indicate that the sustained increase in [Ca2+]c is not an artifact
      introduced by the use of HEPES as an experimental buffer, but rather a normal
      component of the Ang II-stimulated Ca2+ signal.

PMID- 1986183
TI  - Pirenzepine block of ACH-induced mucus secretion in tracheal submucosal gland
      cells.
AB  - Muscarinic stimulation of mucus secretion, as measured by the release of
      [3H]glycoprotein, was studied in explants from the tracheal epithelium of
      weanling swine. The mucus glycoprotein secretion was transient, ceasing within
      the first 10 min of a continuous exposure to 100 microM ACh. Increasing the
      solution's osmotic pressure did not alter basal mucus glycoprotein secretion.
      Mucus glycoprotein secretion was inhibited by 2-10 microM PZP, indicating that
      the M3 muscarinic receptors mediate cholinergic stimulation of mucus production.

PMID- 1986184
TI  - Sexual dimorphism of blood pressure in spontaneously hypertensive rats is
      androgen dependent.
AB  - Intact male and female spontaneously hypertensive rats showed a progressive
      increase in blood pressure with growth; male attained systolic blood pressure
      levels of 244 +/- 6 mmHg, and females 205 +/- 3 mmHg at age 22 weeks.
      Orchidectomy at age 4 weeks significantly attenuated the systolic blood pressure
      elevation in the male (195 +/- 4 mmHg at age 22 weeks), but ovariectomy at age 4
      weeks had no effect on the development of hypertension in the female. The pattern
      of development of hypertension in orchidectomized males was the same as that in
      intact and ovariectomized females. Administration of testosterone propionate to
      gonadectomized rats of both sexes conferred a male pattern of blood pressure
      development. These results indicate that the sexually dimorphic pattern of
      hypertension in the spontaneously hypertensive rat is androgen dependent, rather
      than estrogen dependent. Plasma norepinephrine levels did not differ between the
      sexes, nor were they altered by gonadectomy or testosterone replacement,
      suggesting that the higher blood pressures in the intact male and androgen
      treated male and female SHR are not dependent on increased sympathetic outflow in
      the established phase of hypertension. Stores of norepinephrine in the posterior
      hypothalamic region were significantly greater in intact male rats and
      testosterone treated rats of both sexes than in intact or ovariectomized females,
      and were higher in the pons of intact female rats than in all other groups. These
      alterations in central catecholamine stores were not correlated with blood
      pressure. Further study is needed to assess the functional significance of these
      androgen mediated alterations in posterior hypothalamic neurons as a determinant
      of the androgen mediated sexual dimorphism of blood pressure in the spontaneously
      hypertensive rat.

PMID- 1986185
TI  - Human renin activation by protease from the renin granule fraction of the dog
      kidney cortex.
AB  - To clarify the possible conversion of prorenin in renin granules where conversion
      reportedly occurred, we investigated whether the renin granule fraction of the
      kidney could activate prorenin to the active form. Renin granules were isolated
      from the dog kidney cortex by discontinuous sucrose density gradient
      centrifugation. Human active renin was quantified by immunoradiometric assay
      which could detect only the human active renin but not the inactive human renin
      or dog renin. Inactive renin from human amniotic fluid was incubated with the
      subcellular fraction of the dog kidney cortex. The renin granule fraction that
      showed the highest renin activity stimulated the inactive renin to become the
      active form. The membrane preparation obtained from the renin granule fraction by
      freezing and thawing the fraction in low osmolarity retained the activity of
      renin activation. Other subcellular fractions showed less renin activation. The
      optimal pH for renin activation by the membrane was pH 5.0 to 6.0. The activation
      depended on the time of incubation and concentration. The activation was
      inhibited by N-ethylmaleimide but not by EDTA or serine protease inhibitors.
      These results suggest that renin is processed by a membrane bound protease in
      renin granules.

PMID- 1986186
TI  - Clinical decision analysis.

PMID- 1986188
TI  - Common social problems of adolescents.

PMID- 1986187
TI  - Training for rural practice in Australia 1990.
AB  - There is a shortage of general practitioners in rural Australia. Several recent
      State and federal government reports have highlighted the difficulties of rural
      practice. One of the reasons commonly cited for the shortage of country doctors
      is the lack of appropriate training in Australia's medical schools and the Family
      Medicine Programme. This survey of the heads of departments of community
      medicine/general practice of Australia's 10 medical schools and of the State
      directors of the Family Medicine Programme documents the present efforts to train
      doctors for rural general practice. A 100% response was achieved. The responses
      indicate much interest and effort from the Family Medicine Programme in
      developing rural training schemes. Though the community medicine/general practice
      departments demonstrate considerable interest and innovation, they are hampered
      by lack of resources and negative attitudes of some specialist colleagues.
      Overall, the main impediments are: lack of "affirmative action" admissions
      policies to recruit rural students; insufficient curricular time for teaching the
      principles of general practice; students' lack of confidence in the procedural
      aspects of rural practice; lack of appropriate training posts in anaesthetics;
      lack of appropriate general practice training posts at regional hospitals; and
      lack of financial resources. Some suggestions are given to improve training for
      rural practice in Australia.

PMID- 1986189
TI  - Spotted fever in East Gippsland, Victoria: a previously unrecognised focus of
      rickettsial infection.
AB  - A new focus of spotted fever group rickettsial infection has been recognised in
      East Gippsland, Victoria. Seven cases have been identified among Melbourne
      residents after they holidayed in the area. The infections were confirmed
      serologically. The precise identity of the Rickettsia has not been determined.

PMID- 1986191
TI  - Personal costs incurred by women attending a mammographic screening programme.
AB  - A survey of the personal costs (travel and time) incurred by 150 randomly
      selected women attending a mammographic screening programme indicated that 74%
      travelled by car and 78 (52%) were accompanied by another person. Of the 78
      accompanying persons 16 also had a breast x-ray. Fifteen women in the survey and
      10 of the unscreened accompanying persons had taken leave from work to attend the
      programme, and this leave was unpaid for five women and two unscreened
      accompanying persons. The mean travel costs, out-of-pocket expenses, and
      opportunity costs per attendance were $6.45, $8.14, and $13.75, respectively. The
      personal costs involved in attending a screening programme appear to be
      substantial and may deter women from attending.

PMID- 1986190
TI  - Breast cancer diagnosis by screening mammography: early results of the Central
      Sydney Area Health Service Breast X-ray Programme.
AB  - The Central Sydney Area Health Service (CSAHS) Breast X-ray Programme is a pilot
      mammography screening project for breast cancer detection funded by the NSW
      Government. Screening by two-view mammography is carried out in a mobile van and
      is offered free to women aged over 45 years living in the CSAHS region, the inner
      western suburbs of Sydney. In the first 18 months of operation from March 1988,
      7193 women were screened: 99 women underwent excision biopsy and 53 cancers were
      diagnosed. This is an overall detection rate of seven cancers per thousand women
      screened. Sixty per cent of the cancers were impalpable to the examining surgeon;
      19% of all cancers were shown to have axillary node metastasis at the time of
      diagnosis. These results compare well with those of the major European screening
      studies.

PMID- 1986192
TI  - The use of bone mass screening to prevent fractures.

PMID- 1986193
TI  - Computerised information exchange in health care.
AB  - The slowly increasing use of computers in the management of general medical
      practices may be greatly accelerated if new technologies for the storage and
      transfer of information are introduced. Electronic data interchange promises to
      speed the transfer of medical data, insurance information and payments. Smart
      cards promise a portable, up-to-date, confidential medical record that can be
      carried by patients. However attractive these new systems may be to computer
      suppliers and government bureaucracies, it is not certain that they will be as
      attractive for the general practitioners who will be required to implement the
      changes. Smart cards may exacerbate problems with the ownership and privacy of
      data, rather than guaranteeing confidentiality and control. Data exchange through
      a computer network may allow many information services not actually essential to
      general practice, while creating serious new possibilities for breaches of
      privacy. Costs in implementing the new technologies for general practices may
      outweigh any gains in efficiency, which could in any case be achieved through
      better use of paper records. The Health Insurance Commission may see advantages
      in the collection of data on the diagnoses of patients that can be used in
      epidemiological studies and in the control of overservicing, but there will be
      practical limitations on the reliability of the data collected by this means.
      General practitioners should carefully consider their attitude to these new
      technologies before suppliers, governments and others make their record-keeping
      decisions for them.

PMID- 1986194
TI  - Anal size in children.

PMID- 1986195
TI  - Problems facing the teaching hospitals.

PMID- 1986196
TI  - Antibiotics for otitis externa.

PMID- 1986197
TI  - The cost of a medical student to country parents.

PMID- 1986198
TI  - The injecting and sexual behaviour of intravenous drug users.

PMID- 1986199
TI  - Breast cancer screening: "one swallow doth not a summer make".

PMID- 1986200
TI  - Intraoperative spinal cord monitoring.

PMID- 1986201
TI  - Computers in practice.

PMID- 1986202
TI  - Rational microeconomics in medicine?

PMID- 1986203
TI  - Monitoring spinal cord function during scoliosis surgery with Cotrel-Dubousset
      instrumentation.
AB  - Cotrel-Dubousset instrumentation has been a major advance in spinal surgery but,
      at least theoretically, it carries a higher risk of spinal cord damage. This
      paper describes our experience in monitoring the function of either ascending
      sensory pathways or both ascending sensory and descending motor pathways in the
      spinal cord during such procedures. Seventy-nine juvenile and adult patients are
      presented in whom either somatosensory recording (n = 39) or simultaneous
      corticospinal and somatosensory monitoring (n = 40) was attempted by means of
      epidural electrodes during corrective surgery with Cotrel-Dubousset
      instrumentation. Abnormal evoked responses were seen in two cases but these
      resolved in both before the operation was completed. No new neurological deficits
      occurred nor were any pre-existing deficits increased.

PMID- 1986204
TI  - Tuberculosis in New South Wales.
AB  - Surveillance of tuberculosis in New South Wales depends on notification of cases
      by medical practitioners and careful follow-up by public health nurses dedicated
      to the control of tuberculosis. Evaluation of tuberculosis surveillance data
      enables identification of patterns of infection, highlighting areas requiring
      specific interventions. In 1986, 290 cases of tuberculosis were notified to the
      Department of Health, New South Wales. The majority of patients (72.8%) were
      diagnosed as having pulmonary disease. The highest rates of infection were in
      people from Southeast Asian countries. Whereas 5.2% of cases were identified when
      the patients entered Australia, a substantial proportion of diagnoses (23.1%)
      were made in people who had been resident in Australia for 10 or more years. This
      article highlights the need to continue efforts to improve tuberculosis
      surveillance and control programmes in New South Wales.

PMID- 1986205
TI  - Inconsistencies in statistics of deaths from AIDS.
AB  - From 1983 to 1988 there were 396 registrations of death certified as caused by
      immunodeficiencies including the acquired immunodeficiency syndrome (AIDS).
      Detailed examination of other death registration data yields an estimate of 692
      deaths in this period from AIDS and its sequelae. Over the same period, 617
      notified AIDS patients are known to have died. The data sources can be reasonably
      closely reconciled for the years 1983 to 1987, but there is an unexplained
      shortfall in reporting of deaths of notified AIDS patients in 1988. A study which
      matches notifications and death registrations for the same individuals is needed
      to explain these findings, which have implications for statistics of survival
      times in AIDS and for estimates of the size of the epidemic.

PMID- 1986206
TI  - Renal disease presenting as severe unremitting colic.
AB  - We made a retrospective study of 1770 infants with colic. Of these infants 206
      were classified as having severe colic. Six of the infants with severe colic
      failed to respond to intensive behaviour management and were found to have
      urinary infection. Later investigation revealed that all six had significant
      renal disease. We recommend that all infants with colic who do not respond
      rapidly to conventional management be investigated for urinary tract infections.

PMID- 1986207
TI  - Flinders Island spotted fever: a newly recognised endemic focus of tick typhus in
      Bass Strait. Part 1. Clinical and epidemiological features.
AB  - Twenty six cases of a spotted-fever-like illness have been identified over a 17
      year period in the population of about 1000 of Flinders Island, Tasmania. The
      usual features were high fever, headache, myalgia, slight cough, arthralgia
      without joint swelling and a maculopapular rash which did not resemble the common
      exanthems. Twelve cases had a focal skin lesions. Available evidence implicates
      ticks as the vector.

PMID- 1986209
TI  - Laser coronary angioplasty.

PMID- 1986208
TI  - H. influenzae vaccine for infants.

PMID- 1986210
TI  - Gamma hydroxy butyrate poisoning.

PMID- 1986211
TI  - Inhalation abuse of fentanyl.

PMID- 1986212
TI  - Nutritional guidelines for pregnant women.

PMID- 1986213
TI  - Quarterly AIDS map.

PMID- 1986214
TI  - Expression of wild-type p53 is not compatible with continued growth of p53
      negative tumor cells.
AB  - Inactivation of the cellular p53 gene is a common feature of Friend virus-induced
      murine erythroleukemia cell lines and may represent a necessary step in the
      progression of this disease. As well, frequent loss or mutation of p53 alleles in
      diverse human tumors is consistent with the view of p53 as a tumor suppressor
      gene. To examine the significance of p53 gene inactivation in tumorigenesis, we
      have attempted to express transfected wild-type p53 in three p53-negative tumor
      cell lines: murine DP16-1 Friend erythroleukemia cells, human K562 cells, and
      SKOV-3 cells. We found that aberrant p53 proteins, which differ from wild-type
      p53 by a single amino acid substitution, were expressed stably in these cells,
      whereas wild-type p53 expression was not tolerated. The inability of p53-negative
      tumor cell lines to support long-term expression of wild-type p53 protein is
      consistent with the view that p53 is a tumor suppressor gene.

PMID- 1986215
TI  - Tumor suppressor p53: analysis of wild-type and mutant p53 complexes.
AB  - It has been suggested that the dominant effect of mutant p53 on tumor progression
      may reflect the mutant protein binding to wild-type p53, with inactivation of
      suppressor function. To date, evidence for wild-type/mutant p53 complexes
      involves p53 from different species. To investigate wild-type/mutant p53
      complexes in relation to natural tumor progression, we sought to identify
      intraspecific complexes, using murine p53. The mutant phenotype p53-246(0) was
      used because this phenotype is immunologically distinct from wild-type p53-246+
      and thus permits immunological analysis for wild-type/mutant p53 complexes. The
      p53 proteins were derived from genetically defined p53 cDNAs expressed in vitro
      and also from phenotypic variants of p53 expressed in vivo. We found that the
      mutant p53 phenotype was able to form a complex with the wild type when the two
      p53 variants were cotranslated. When mixed in their native states (after
      translation), the wild-type and mutant p53 proteins did not exhibit any binding
      affinity for each other in vitro. Under identical conditions, complexes of wild
      type human and murine p53 proteins were formed. For murine p53, both the wild
      type and mutant p53 proteins formed high-molecular-weight complexes when
      translated in vitro. This oligomerization appeared to involve the carboxyl
      terminus, since truncated p53 (amino acids 1 to 343) did not form complexes. We
      suggest that the ability of the mutant p53 phenotype to complex with wild type
      during cotranslation may contribute to the transforming function of activated
      mutants of p53 in vivo.

PMID- 1986216
TI  - Isolation and characterization of PKC-L, a new member of the protein kinase C
      related gene family specifically expressed in lung, skin, and heart.
AB  - We have isolated and characterized a new human cDNA, coding for a protein kinase,
      related to the protein kinase C (PKC) gene family. Although this protein kinase
      shares some homologous sequences and structural features with the four members of
      the PKC family initially isolated (alpha, beta I, beta II, and gamma), it shows
      more homology with the recently described PKC-related subfamily, encoded by the
      cDNAs delta, epsilon, and zeta. The transcript for this gene product, termed PKC
      L, is most abundant in lung tissue, less expressed in heart and skin tissue, and
      exhibited very low expression in brain tissue. Thus, its tissue distribution is
      different from that described for other mammalian members of the PKC gene family,
      their expression being enriched in brain tissues. PKC-L is also expressed in
      several human cell lines, including the human epidermoid carcinoma line A431. The
      ability of phorbol esters to bind to and stimulate the kinase activity of PKC-L
      was revealed by introducing the cDNA into COS cells.

PMID- 1986217
TI  - In vivo genomic footprint of a yeast centromere.
AB  - We have used in vivo genomic footprinting to investigate the protein-DNA
      interactions within the conserved DNA elements (CDEI, CDEII, and CDEIII) in the
      centromere from chromosome III of the yeast Saccharomyces cerevisiae. The in vivo
      footprint pattern obtained from wild-type cells shows that some guanines within
      the centromere DNA are protected from methylation by dimethyl sulfate. These
      results are consistent with studies demonstrating that yeast cells contain
      sequence-specific centromere DNA-binding proteins. Our in vivo experiments on
      chromosomes with mutant centromeres show that some mutations which affect
      chromosome segregation also alter the footprint pattern caused by proteins bound
      to the centromere DNA. The results of this study provide the first fine-structure
      map of proteins bound to centromere DNA in living yeast cells and suggest a
      direct correlation between these protein-DNA interactions and centromere
      function.

PMID- 1986219
TI  - Cell cycle-dependent variations in deoxyribonucleotide metabolism among Chinese
      hamster cell lines bearing the Thy- mutator phenotype.
AB  - Deoxyribonucleotide pool imbalances are frequently mutagenic. We have studied two
      Chinese hamster ovary cell lines, Thy- 49 and Thy- 303, that were originally
      characterized by M. Meuth (Mol. Cell. Biol. 1:652-660, 1981). In comparison with
      wild-type CHO cells, both lines have elevated dCTP/dTTP ratios, resulting from
      loss of feedback control of CTP synthetase. While asynchronous cultures of both
      cell lines contain nearly identical deoxyribonucleoside triphosphate (dNTP) pools
      and both display elevated spontaneous mutation frequencies, the mutation
      frequencies between the two cell lines differ by as much as 10-fold. We asked
      whether differences in dNTP pools could be seen in extracts of rapidly isolated
      nuclei. Small differences, probably not large enough to account for the
      differences in mutation frequencies, were seen. However, when synchronized S
      phase-enriched cell populations were examined, substantial differences were seen,
      both in whole-cell extracts and in nuclear extracts. Thy- 303 cells, which have
      higher mutation frequencies than do Thy- 49 cells, also showed the more aberrant
      dNTP pools. These data indicate that the Thy- 303 line contains a second mutation
      in addition to the mutation affecting CTP synthetase control. Evidence suggests
      that this putative second mutation affects an allosteric regulatory site of
      ribonucleotide reductase. The data on intranuclear dNTP pools in synchronized S
      phase cells indicate that higher proportions of cellular dATP and dGTP are found
      in the nucleus than are corresponding amounts of dCTP and dGTP. Thus, despite the
      porous nature of the nuclear membrane, there are conditions under which the
      distributions of deoxyribonucleotides across this membrane are not random.

PMID- 1986218
TI  - Macronuclei and micronuclei in Tetrahymena thermophila contain high-mobility
      group-like chromosomal proteins containing a highly conserved eleven-amino-acid
      putative DNA-binding sequence.
AB  - HMG (high-mobility-group protein) B and HMG C are abundant nonhistone chromosomal
      proteins isolated from Tetrahymena thermophila macronuclei with solubilities,
      molecular weights, and amino acid compositions like those of vertebrate HMG
      proteins. Genomic clones encoding each of these proteins have been sequenced.
      Both are single-copy genes that encode single polyadenylated messages whose
      amounts are 10 to 15 times greater in growing cells than in starved, nongrowing
      cells. The derived amino acid sequences of HMG B and HMG C contain a highly
      conserved sequence, the HMG 1 box, found in vertebrate HMGs 1 and 2, and we
      speculate that this sequence may represent a novel, previously unrecognized DNA
      binding motif in this class of chromosomal proteins. Like HMGs 1 and 2, HMGs B
      and C contain a high percentage of aromatic amino acids. However, the Tetrahymena
      HMGs are small, are associated with nucleosome core particles, and can be
      specifically extracted from macronuclei by elutive intercalation, properties
      associated with vertebrate HMGs 14 and 17, not HMGs 1 and 2. Thus, it appears
      that these Tetrahymena proteins have features in common with both of the major
      subgroups of higher eucaryotic HMG proteins. Surprisingly, a linker histone found
      exclusively in transcriptionally inactive micronuclei also has several HMG-like
      characteristics, including the ability to be specifically extracted from nuclei
      by elutive intercalation and the presence of the HMG 1 box. This finding suggests
      that at least in T. thermophila, proteins with HMG-like properties are not
      restricted to regions of transcriptionally active chromatin.

PMID- 1986221
TI  - A chicken beta-actin gene can complement a disruption of the Saccharomyces
      cerevisiae ACT1 gene.
AB  - Recently it was demonstrated that beta-actin can be produced in Saccharomyces
      cerevisiae by using the expression plasmid pY beta actin (R. Karlsson, Gene
      68:249-258, 1988), and several site-specific mutants are now being produced in a
      protein engineering study. To establish a system with which recombinant actin
      mutants can be tested in vivo and thus enable a correlation to be made with
      functional effects observed in vitro, a yeast strain lacking endogenous yeast
      actin and expressing exclusively beta-actin was constructed. This strain is
      viable but has an altered morphology and a slow-growth phenotype and is
      temperature sensitive to the point of lethality at 37 degrees C.

PMID- 1986220
TI  - SDC25, a CDC25-like gene which contains a RAS-activating domain and is a
      dispensable gene of Saccharomyces cerevisiae.
AB  - In the yeast Saccharomyces cerevisiae, the CDC25 gene product activates adenylate
      cyclase through RAS1 and RAS2 gene products. We have recently described the
      cloning of a DNA fragment which suppresses the cdc25 mutation but not ras1, ras2,
      or cdc35 mutations. This fragment contains a 5'-truncated open reading frame
      which shares 47% identity with the C-terminal part of the CDC25 gene. We named
      the entire gene SDC25. In this paper, we report the cloning, sequencing, and
      characterization of the complete SDC25 gene. The SDC25 gene is located on the
      chromosome XII close to the centromere. It is transcribed into a 4-kb-long mRNA
      that contains an open reading frame of 1,251 codons. Homology with the CDC25 gene
      extends in the N-terminal part, although the degree of similarity is lower than
      in the C-terminal part. In contrast with the C-terminal part, the complete SDC25
      gene was found not to suppress the CDC25 gene defect. A deletion in the N
      terminal part restored the suppressing activity, a result which suggests the
      existence of a regulatory domain. The SDC25 gene was found to be dispensable for
      cell growth under usual conditions. No noticeable phenotype was found in the
      deleted strain.

PMID- 1986222
TI  - The yeast rad18 mutator specifically increases G.C----T.A transversions without
      reducing correction of G-A or C-T mismatches to G.C pairs.
AB  - Inactivation of the Saccharomyces cerevisiae RAD18 gene confers a mutator
      phenotype. To determine the specificity of this effect, a collection of 212
      spontaneous SUP4-o mutants arising in a rad18 strain was characterized by DNA
      sequencing. Comparison of the resulting mutational spectrum with that for an
      isogenic wild-type (RAD18) strain revealed that the rad18 mutator specifically
      enhanced the frequency of single base pair substitutions. Further analysis
      indicated that an increase in the frequency of G.C----T.A transversions accounted
      for the elevated SUP4-o mutation frequency. Thus, rad18 is the first eucaryotic
      mutator found to generate only a particular base pair substitution. The majority
      of G.C pairs that were not mutated in the rad18 background were at sites where
      G.C----T.A events can be detected in SUP4-o, suggesting that DNA sequence context
      influences the rad18 mutator effect. Transformation of heteroduplex plasmid DNAs
      into the two strains demonstrated that the rad18 mutator did not reduce the
      efficiency of correcting G-A or C-T mismatches to G.C pairs or preferentially
      correct the mismatches to A.T pairs. We propose that the RAD18 gene product might
      contribute to the fidelity of DNA replication in S. cerevisiae by involvement in
      a process that serves to limit the formation of G-A and C-T mismatches at
      template guanine and cytosine sites during DNA synthesis.

PMID- 1986223
TI  - Structure and regulation of histone H2B mRNAs from Leishmania enriettii.
AB  - We have studied the structure and expression of histone H2B mRNA and genes in the
      parasitic protozoan Leishmania enrietti. A genomic clone containing three
      tandemly repeated genes has been sequenced and shown to encode three identical
      histone proteins and two types of closely related mRNA sequence. We have also
      sequenced three independent cDNA clones and demonstrated that the Leishmania H2B
      mRNAs are polyadenylated, similar to the basal histone mRNAs of higher eucaryotes
      and the histone mRNAs of yeast. In addition, the Leishmania mRNAs contain
      inverted repeats near the poly(A) tail which could form stem-loops similar in
      secondary structure, but not in sequence, to the 3' stem-loops of
      nonpolyadenylated replication-dependent histones of higher eucaryotes. Unlike the
      replication-dependent histones, the Leishmania histone H2B mRNAs do not decrease
      in abundance following treatment with inhibitors of DNA synthesis. The histone
      mRNAs are differentially expressed during the parasite life cycle and accumulate
      to a higher level in the extracellular promastigotes (the form which in nature
      lives within the gut of the insect vector) than in the intracellular amastigotes
      (the form that lives within the mammalian host macrophages).

PMID- 1986224
TI  - Maintenance of NF-kappa B activity is dependent on protein synthesis and the
      continuous presence of external stimuli.
AB  - The activation of NF-kappa B-like activities (called NF-kappa B) by tumor
      necrosis factor alpha (TNF alpha) and the phorbol ester phorbol 12-myristate 13
      acetate (PMA) were compared. High levels of NF-kappa B activity were found 2 to 4
      min after TNF alpha addition to human HL60 cells and lasted for at least 3 h,
      although the half-life of active NF-kappa B was less than 30 min. Inactive NF
      kappa B, however, was relatively stable. NF-kappa B activation by TNF alpha was
      initially cycloheximide insensitive, but maintenance of NF-kappa B activity
      required ongoing protein synthesis and continuous stimulation by TNF alpha. Thus,
      the cells did not remain in an activated state without stimulation. In HL60
      cells, NF-kappa B induction by PMA required 30 to 45 min and was completely
      dependent on de novo protein synthesis, while PMA (and interleukin-1) induced NF
      kappa B activity rapidly in mouse 70Z/3 cells via a protein synthesis-independent
      mechanism. The NF-kappa B-like activities obtained under each condition behaved
      identically in methylation interference and native proteolytic fingerprinting
      assays. The NF-kappa B-like factors induced are thus all very similar or
      identical. We suggest that cell-specific differences in the protein kinase C
      dependent activation of NF-kappa B may exist and that TNF alpha and PMA may
      induce expression of the gene(s) encoding NF-kappa B.

PMID- 1986225
TI  - Regulation of heat shock factor in Schizosaccharomyces pombe more closely
      resembles regulation in mammals than in Saccharomyces cerevisiae.
AB  - The heat shock response appears to be universal. All eucaryotes studied encode a
      protein, heat shock factor (HSF), that is believed to regulate transcription of
      heat shock genes. This protein binds to a regulatory sequence, the heat shock
      element, that is absolutely conserved among eucaryotes. We report here the
      identification of HSF in the fission yeast Schizosaccharomyces pombe. HSF binding
      was not observed in extracts from normally growing S. pombe (28 degrees C) but
      was detected in increasing amounts as the temperature of heat shock increased
      between 39 and 45 degrees C. This regulation is in contrast to that observed in
      Saccharomyces cerevisiae, in which HSF binding is detectable at both normal and
      heat shock temperatures. The S. pombe factor bound specifically to the heat shock
      element, as judged by methylation interference and DNase I protection analysis.
      The induction of S. pombe HSF was not inhibited by cycloheximide, suggesting that
      induction occurs posttranslationally, and the induced factor was shown to be
      phosphorylated. S. pombe HSF was purified to near homogeneity and was shown to
      have an apparent mobility of approximately 108 kDa. Since heat-induced DNA
      binding by HSF had previously been demonstrated only in metazoans, the
      conservation of heat-induced DNA binding by HSF among S. pombe and metazoans
      suggests that this mode of regulation is evolutionarily ancient.

PMID- 1986226
TI  - The strong ADH1 promoter stimulates mitotic and meiotic recombination at the ADE6
      gene of Schizosaccharomyces pombe.
AB  - The effect of the strong promoter from the alcohol dehydrogenase gene on mitotic
      and meiotic intragenic recombination has been studied at the ade6 locus of the
      fission yeast Schizosaccharomyces pombe. A 700-bp fragment containing the
      functional adh1 promoter was used to replace the weak wild-type promoter of the
      ade6 gene. Analysis of mRNA showed that strains with this ade6::adh1 fusion
      construct had strongly elevated ade6-specific mRNA levels during vegetative
      growth as well as in meiosis. These increased levels of mRNA correlated with a 20
      to 25-fold stimulation of intragenic recombination in meiosis and a 7-fold
      increased prototroph formation during vegetative growth. Analysis of flanking
      marker configurations of prototrophic recombinants indicated that simple
      conversions as well as conversions associated with crossing over were stimulated
      in meiosis. The strongest stimulation of recombination was observed when the adh1
      promoter was homozygous. Studies with heterologous promoter configurations
      revealed that the highly transcribed allele was the preferred acceptor of genetic
      information. The effect of the recombinational hot spot mutation ade6-M26 was
      also investigated in this system. Its effect was only partly additive to the
      elevated recombination rate generated by the ade6::adh1 fusion construct.

PMID- 1986228
TI  - A poly(dA.dT) tract is a component of the recombination initiation site at the
      ARG4 locus in Saccharomyces cerevisiae.
AB  - An initiation site for meiotic gene conversion is located in the promoter region
      of the ARG4 locus in Saccharomyces cerevisiae. We have tested the hypothesis that
      the initiation site is identical with the promoter by making a series of small
      deletions that remove specific promoter elements. Disruption of most promoter
      elements does not lower the level of gene conversion in ARG4, and analysis of RNA
      levels at the time of recombination in meiosis reveals no direct correlation
      between the level of ARG4 transcript and the level of gene conversion in ARG4.
      However, deletion of a tract of 14 A residues located at the peak of the gene
      conversion gradient decreases the number of gene conversion events stimulated by
      the initiation site to 25 to 35% of the normal level. We conclude that the
      poly(dA.dT) tract is responsible for most but not all of the high levels of
      meiotic gene conversion observed in ARG4.

PMID- 1986227
TI  - Differential compartmentalization of plasmid DNA microinjected into Xenopus
      laevis embryos relates to replication efficiency.
AB  - Circular plasmid DNA molecules and linear concatemers formed from the same
      plasmid exhibit strikingly different fates following microinjection into Xenopus
      laevis embryos. In this report, we prove quantitatively that only a minority of
      small, circular DNA molecules were replicated (mean = 14%) from fertilization
      through the blastula stage of development. At all concentrations tested, very few
      molecules (approximately 1%) underwent more than one round of DNA synthesis
      within these multiple cell cycles. In addition, unlike endogenous chromatin, the
      majority of circular templates became resistant to cleavage by micrococcal
      nuclease. The extent of nuclease resistance was similar for both replicated and
      unreplicated templates. Sequestration of circular molecules within a membranous
      compartment (pseudonucleus), rather than the formation of nucleosomes with
      abnormal size or spacing, apparently conferred the nuclease resistance. In
      contrast, most linearly concatenated DNA molecules (derived from end-to-end
      joining of microinjected monomeric plasmid DNA) underwent at least two rounds of
      DNA replication during this same period. Linear concatemers also exhibited
      micrococcal nuclease digestion patterns similar to those seen for endogenous
      chromatin yet, as judged by their failure to persist in later stages of
      embryogenesis, were likely to be replicated and maintained extrachromosomally. We
      propose, therefore, that template size and conformation determine the efficiency
      of replication of microinjected plasmid DNA by directing DNA to a particular
      compartment within the cell following injection. Template-dependent
      compartmentalization may result from differential localization within endogenous
      nuclei versus extranuclear compartments or from supramolecular assembly processes
      that depend on template configuration (e.g., association with nuclear matrix or
      nuclear envelope).

PMID- 1986229
TI  - Characterization of a short, cis-acting DNA sequence which conveys cell cycle
      stage-dependent transcription in Saccharomyces cerevisiae.
AB  - Comparison of the 5'-flanking regions of several cell cycle-regulated DNA
      replication genes of Saccharomyces cerevisiae has revealed the presence of a
      common sequence, 5'-ACGCGT-3', which is upstream and proximal to mapped
      transcription initiation sites. This sequence, which is the cleavage site for the
      restriction endonuclease MluI, is present twice in the upstream region of the
      yeast thymidylate synthase gene TMP1. Previous studies have implicated these MluI
      sites as critical components in the cell cycle-dependent transcription of TMP1.
      In this study, we examined more closely the importance of the ACGCGT sequences
      for the transcription of this gene. Using site-directed mutagenesis in
      combination with deletion analysis and subcloning experiments, we found that (i)
      while both of the TMP1 MluI sites contribute to the total transcription of this
      gene, the distal site is predominant and (ii) the 9-bp sequence ACGCGTTAA
      encompassing the distal MluI site exhibits properties of a cell cycle-stage
      dependent upstream activation sequence element. The results of this study support
      the notion that the ACGCGT sequence is an integral component of a transcription
      system which coordinates the cell cycle-dependent expression of DNA replication
      genes in S. cerevisiae.

PMID- 1986230
TI  - Transient activity assays of the Trypanosoma brucei variant surface glycoprotein
      gene promoter: control of gene expression at the posttranscriptional level.
AB  - The putative promoter of the variant surface glycoprotein (VSG) gene of
      Trypanosoma brucei was cloned into a plasmid containing the chloramphenicol
      acetyltransferase (CAT) gene. After electroporation into trypanosomes, this
      construct directed the expression of the CAT reporter gene. The essential region
      for promoter activity was found to reside within 88 bp upstream of the putative
      transcription start site. Transcription of the CAT construct occurred at
      approximately the same level in both bloodstream and procyclic forms and was
      resistant to alpha-amanitin. However, CAT expression appeared to be modulated in
      the two forms of the parasite. Sequences 3' to the gene seemed to be important in
      this respect, as CAT activity in bloodstream forms was readily detectable only
      when the 3' region of a VSG cDNA was placed downstream of the CAT gene. Two
      separate VSG gene promoter sequences, both cloned from T. brucei AnTat 1.3A, were
      equally able to direct CAT expression, which suggests that there are a number of
      potential VSG gene promoters in the genome, although usually only one expression
      site is fully active at any one time.

PMID- 1986231
TI  - Isolation, nucleotide sequence analysis, and disruption of the MDH2 gene from
      Saccharomyces cerevisiae: evidence for three isozymes of yeast malate
      dehydrogenase.
AB  - The major nonmitochondrial isozyme of malate dehydrogenase (MDH2) in
      Saccharomyces cerevisiae cells grown with acetate as a carbon source was purified
      and shown by sodium dodecyl sulfate-polyacrylamide gel electrophoresis to have a
      subunit molecular weight of approximately 42,000. Enzyme assays and an antiserum
      prepared against the purified protein were used to screen a collection of acetate
      nonutilizing (acetate-) yeast mutants, resulting in identification of mutants in
      one complementation group that lack active or immunoreactive MDH2. Transformation
      and complementation of the acetate- growth phenotype was used to isolate a
      plasmid carrying the MDH2 gene from a yeast genomic DNA library. The amino acid
      sequence derived from complete nucleotide sequence analysis of the isolated gene
      was found to be extremely similar (49% residue identity) to that of yeast
      mitochondrial malate dehydrogenase (molecular weight, 33,500) despite the
      difference in sizes of the two proteins. Disruption of the MDH2 gene in a haploid
      yeast strain produced a mutant unable to grow on minimal medium with acetate or
      ethanol as a carbon source. Disruption of the MDH2 gene in a haploid strain also
      containing a disruption in the chromosomal MDH1 gene encoding the mitochondrial
      isozyme produced a strain unable to grow with acetate but capable of growth on
      rich medium with glycerol as a carbon source. The detection of residual malate
      dehydrogenase activity in the latter strain confirmed the existence of at least
      three isozymes in yeast cells.

PMID- 1986232
TI  - Intramitochondrial functions regulate nonmitochondrial citrate synthase (CIT2)
      expression in Saccharomyces cerevisiae.
AB  - We have examined the effects of perturbation of mitochondrial function on
      expression of two nuclear genes encoding the mitochondrial and peroxisomal forms
      of citrate synthase in Saccharomyces cerevisiae, CIT1 and CIT2. CIT2 expression
      was as much as 30-fold higher in [rho0] petites, than in isochromosomal [rho+]
      cells, whereas CIT1 expression was slightly down regulated in [rho0] cells. CIT2
      expression was also increased in [rho+] cells by inhibition of respiration with
      antimycin A or in [rho+] cells containing a disruption of the CIT1 gene. These
      effects were additive, and together they approached the level of CIT2 expression
      seen in [rho0] cells. Experiments using heterologous gene fusions showed that all
      of the effects leading to increased expression of CIT2 were transcriptionally
      controlled through 5'-flanking CIT2 DNA sequences. Analysis of [rho+] and [rho0]
      cells containing disruptions of CIT1 and CIT2, singly and in combination, showed
      that the peroxisomal citrate synthase could partially spare the mitochondrial
      isoform for growth yield in [rho+] but not in [rho0] cells. These studies suggest
      a physiological role for increased expression of CIT2 in cells with altered
      mitochondrial function. They also provide additional evidence for a retrograde
      path of communication from mitochondria to the nucleus in yeast cells.

PMID- 1986233
TI  - The immediate-early growth response in regenerating liver and insulin-stimulated
      H-35 cells: comparison with serum-stimulated 3T3 cells and identification of 41
      novel immediate-early genes.
AB  - Liver regeneration provides a unique system for analysis of mitogenesis in
      intact, fully developed animals. Cellular immediate-early genes likely play an
      important role in cell cycle regulation and have been extensively studied in
      mitogen-stimulated fibroblasts lymphocytes but not in liver. We have begun to
      characterize the immediate-early growth response genes of mitogen-stimulated
      liver cells, specifically, regenerating liver and insulin-stimulated Reuber H-35
      hepatoma cells, and to address differences in growth response between different
      cell types. Through subtraction and differential screening of cDNA libraries from
      regenerating liver and insulin-treated H-35 cells, we have extensively
      characterized 341 differentially expressed clones and identified 52 immediate
      early genes. These genes have been partially sequenced and subjected to Northern
      (RNA) blot analysis, and 41 appear to be novel. Surprisingly, two-thirds of these
      genes are also expressed in BALB/c 3T3 cells, but only 10 were identified in
      previous studies of 3T3 cells, and of these, 6 include well-known genes like jun
      and fos, and only 4 are novel. Approximately one-third of the immediate-early
      genes identified in mitogen-stimulated liver cells or serum-stimulated NIH 3T3
      cells are expressed in a tissue-specific fashion, indicating that cell type
      specific regulation of the proliferative response occurs during the immediate
      early period. Our findings indicate that the immediate-early response is
      unusually complex for the first step in a regulatory cascade, suggesting that
      multiple pathways must be activated. The abundance of immediate-early genes and
      the highly varied pattern of their expression in different cell types suggest
      that the tissue specificity of the proliferative response arises from the
      particular set of these genes expressed in a given tissue.

PMID- 1986234
TI  - Two different mutants blocked in synthesis of dolichol-phosphoryl-mannose do not
      add glycophospholipid anchors to membrane proteins: quantitative correction of
      the phenotype of a CHO cell mutant with tunicamycin.
AB  - The addition of glycophospholipid (GPL) anchors to certain membrane proteins
      occurs in the rough endoplasmic reticulum and is essential for transport of the
      proteins to the plasma membrane. Limited circumstantial evidence suggests that
      dolichol-phosphoryl-mannose (DPM) is a donor of mannose residues of these
      anchors. We here report studies of a CHO cell mutant (B421) transfected to
      express the GPL-anchored protein, placental alkaline phosphatase (AP). Only a few
      transfectants were found to express GPL-anchored AP on their surface, and these
      clones synthesized DPM. Moreover, and most strikingly, when surface AP-negative
      transfectants were treated with tunicamycin to cause accumulation of DPM, these
      cells expressed lipid-anchored AP. Fusion of a cloned surface AP-negative
      transfectant of B421 with the Thy-1-class E mutant thymoma, which is also
      deficient in DPM synthesis, produced hybrids that synthesized DPM and expressed
      AP and Thy-1. Thus, two mutations can interrupt DPM synthesis, and three sets of
      observations point to an essential role of DPM for addition of GPL anchors.

PMID- 1986235
TI  - Role of the ligand in intracellular receptor function: receptor affinity
      determines activation in vitro of the latent dioxin receptor to a DNA-binding
      form.
AB  - To reconstitute the molecular mechanisms underlying the cellular response to
      soluble receptor ligands, we have exploited a cell-free system that exhibits
      signal- (dioxin-)induced activation of the latent cytosolic dioxin receptor to an
      active DNA-binding species. The DNA-binding properties of the in vitro-activated
      form were qualitatively indistinguishable from those of in vivo-activated nuclear
      receptor extracted from dioxin-treated cells. In vitro activation of the receptor
      by dioxin was dose dependent and was mimicked by other dioxin receptor ligands in
      a manner that followed the rank order of their relative affinities for the
      receptor in vitro and their relative potencies to induce target gene
      transcription in vivo. Thus, in addition to triggering the initial release of
      inhibition of DNA binding and presumably allowing nuclear translocation, the
      ligand appears to play a crucial role in the direct control of the level of
      functional activity of a given ligand-receptor complex.

PMID- 1986236
TI  - The Xenopus B1 factor is closely related to the mammalian activator USF and is
      implicated in the developmental regulation of TFIIIA gene expression.
AB  - The Xenopus laevis TFIIIA promoter contains a motif that has been implicated in
      promoter activation in late-stage oocytes and contains the sequence (-269) CACGTG
      (-264). A cDNA encoding a protein (B1) that binds to this element has been cloned
      from X. laevis and Xenopus borealis ovarian cDNA libraries. We show that this
      protein is a member of the helix-loop-helix family of regulatory proteins and
      contains 80% sequence identity with the human adenovirus major late transcription
      factor (MLTF or USF). A survey of B1 protein expression during oogenesis and
      embryogenesis revealed both oocyte-specific and somatic cell-specific B1 protein
      DNA complexes. Immunological data, RNA blot analysis, and proteolytic clipping
      band shift assays indicated that these complexes most likely represent altered
      forms of a single B1 polypeptide. Implications for TFIIIA gene regulation during
      development are discussed.

PMID- 1986239
TI  - Repair of deletions and double-strand gaps by homologous recombination in a
      mammalian in vitro system.
AB  - We have designed an in vitro system using mammalian nuclear extracts, or
      fractions derived from them, that can restore the sequences missing at double
      strand breaks (gaps) or in deletions. The recombination substrates consist of (i)
      recipient DNA, pSV2neo with gaps or deletions ranging from 70 to 390 bp in the
      neo sequence, and (ii) donor DNAs with either complete homology to the recipient
      (pSV2neo) or plasmids whose homology with pSV2neo is limited to a 1.0- to 1.3-kbp
      neo segment spanning the gaps or deletions. Incubation of these substrates with
      various enzyme fractions results in repair of the recipient DNA's disrupted neo
      gene. The recombinational repair was monitored by transforming recA Escherichia
      coli to kanamycin resistance and by a new assay which measures the extent of DNA
      strand transfer from the donor substrate to the recipient DNA. Thus, either
      streptavidin- or antidigoxigenin-tagged beads are used to separate the
      biotinylated or digoxigeninylated recipient DNA, respectively, after incubation
      with the isotopically labeled donor DNA. In contrast to the transfection assay,
      the DNA strand transfer measurements are direct, quantitative, rapid, and easy,
      and they provide starting material for the characterization of the recombination
      products and intermediates. Accordingly, DNA bound to beads serves as a suitable
      template for the polymerase chain reaction. With appropriate pairs of
      oligonucleotide primers, we have confirmed that both gaps and deletions are fully
      repaired, that deletions can be transferred from the recipient DNA to the donor's
      intact neo sequence, and that cointegrant molecules containing donor and
      recipient DNA sequences are formed.

PMID- 1986238
TI  - Mechanism of endogenous myc gene down-regulation in E mu-N-myc tumors.
AB  - Transgenic mouse lines carrying the N-myc oncogene deregulated by the
      immunoglobulin heavy-chain enhancer spontaneously develop B-lymphoid tumors (R.
      Dildrop, A. Ma, K. Zimmerman, E. Hsu, A. Tesfaye, R. DePinho, and F. W. Alt, EMBO
      J. 8:1121-1128, 1989; H. Rosenbaum, E. Webb, J. M. Adams, S. Cory, and A. W.
      Harris, EMBO J. 8:749-755). Permanent cell lines derived from these tumors (E mu
      N-myc cell lines) express extremely high levels of the N-myc transgene but little
      or no detectable endogenous N-myc or c-myc. We have employed nuclear run-on
      assays to show that down-regulation of endogenous N- and c-myc expression occurs
      at the transcriptional level. To determine whether the lack of endogenous myc
      gene transcription is a direct effect of high-level N-myc transgene expression,
      we have generated Abelson murine leukemia virus (A-MuLV)-transformed cell lines
      from prelymphomatous E mu-N-myc mice (A-MuLV/E mu-N-myc cell lines). Although
      these A-MuLV/E mu-N-myc lines express very high levels of the N-myc transgene,
      they continue to transcribe the endogenous c-myc gene. These findings demonstrate
      that high-level N-myc gene expression alone does not necessarily lead to down
      regulation of endogenous myc gene expression and suggest that events associated
      with transformation by N-myc may be critical to this process.

PMID- 1986237
TI  - In vivo pre-tRNA processing in Saccharomyces cerevisiae.
AB  - We have surveyed intron-containing RNAs of the yeast Saccharomyces cerevisiae by
      filter hybridization with pre-tRNA intron-specific oligonucleotide probes. We
      have classified various RNAs as pre-tRNAs, splicing intermediates, or excised
      intron products according to apparent size and structure. Linear, excised intron
      products were detected, and one example was isolated and sequenced directly.
      Additional probes designed to detect other precursor sequences were used to
      verify the identification of several intermediates. Pre-tRNA species with both 5'
      leader and 3' extension, with 3' extension only, and with mature ends were
      distinguished. From these results, we conclude that the processing reactions used
      to remove the 5' leader and 3' extension from the transcript are ordered 5' end
      trimming before 3' end trimming. Splicing intermediates containing the 5' exon
      plus the intron were detected. The splice site cleavage reactions are probably
      ordered 3' splice site cleavage before 5' splice site cleavage. Surprisingly, we
      also detected a splicing intermediate with the 5' leader and a spliced product
      with both 5' leader and 3' extension. Evidently, splicing and end trimming are
      not ordered relative to each other, splicing occurring either before or after end
      trimming.

PMID- 1986240
TI  - Sequence organization and RNA structural motifs directing the mouse primary rRNA
      processing event.
AB  - The first processing step in the maturation of mouse precursor rRNA involves
      cleavage at nucleotide ca. +650, at the 5' border of a 200-nucleotide region that
      is conserved across mammals and contains the sequences that direct the
      processing. To identify the relevant sequence elements, we used rRNAs with small
      internal mutations and short pre-rRNA substrates. Much of the region can be
      mutated without appreciable effect, but nucleotides +655 to +666 appear to be
      absolutely required and short segments surrounding +750 and +810 markedly
      stimulate processing. The minimal processing signal corresponds to rRNA
      nucleotides +645 to +672. Formation of a ribonucleoprotein complex of retarded
      electrophoretic mobility is evidently necessary but not sufficient for
      processing. Computer-assisted analysis suggested a phylogenetic- and mutant
      supported secondary structure in which the minimal processing signal forms a stem
      with the +655 region in the loop, and there is a separate branched duplex
      containing the downstream stimulatory sequences. Use of antisense RNA, in trans
      and in cis, to sequester the +655 region in a duplex supported the hypothesis
      that this critical region was needed in a single-stranded conformation for
      processing and for specific complex formation.

PMID- 1986241
TI  - ACE2, an activator of yeast metallothionein expression which is homologous to
      SWI5.
AB  - Transcription of the Saccharomyces cerevisiae metallothionein gene CUP1 is
      induced in response to high environmental levels of copper. Induction requires
      the ACE1 gene product, which binds to specific sites in the promoter region of
      the CUP1 gene. In this study, we found that deleting the entire coding sequence
      of the ACE1 gene resulted in a decrease in basal-level transcription of CUP1 to
      low but detectable levels and conferred a copper-sensitive phenotype to the
      cells. We have isolated a gene, designated ACE2, which when present on a high
      copy-number plasmid suppresses the copper-sensitive phenotype of an ace1-deletion
      strain. The presence of multiple copies of the ACE2 gene enhanced expression of
      an unlinked CUP1-lacZ fusion integrated in the yeast genome and resulted in an
      increase in the steady-state levels of CUP1 mRNA in an ace1-deletion background.
      A large deletion of the coding region of the genomic copy of ACE2 resulted in a
      decrease in steady-state levels of CUP1 mRNA, indicating that ACE2 plays a role
      in regulating basal-level expression of CUP1. The ACE2 open reading frame encodes
      a polypeptide of 770 amino acids, with putative zinc finger structures near the
      carboxyl terminus. This protein is 37% identical to the SWI5 gene product, an
      activator of HO gene transcription in S. cerevisiae, suggesting that ACE2 and
      SWI5 may have functional similarities.

PMID- 1986242
TI  - Suppression of ribosomal reinitiation at upstream open reading frames in amino
      acid-starved cells forms the basis for GCN4 translational control.
AB  - GCN4 encodes a transcriptional activator of amino acid-biosynthetic genes in
      Saccharomyces cerevisiae that is regulated at the translational level by upstream
      open reading frames (uORFs) in its mRNA leader. uORF4 (counting from the 5' end)
      is sufficient to repress GCN4 under nonstarvation conditions; uORF1 is required
      to overcome the inhibitory effect of uORF4 and stimulate GCN4 translation in
      amino acid-starved cells. Insertions of sequences with the potential to form
      secondary structure around uORF4 abolish derepression, indicating that ribosomes
      reach GCN4 by traversing uORF4 sequences rather than by binding internally to the
      GCN4 start site. By showing that wild-type regulation occurred even when uORF4
      was elongated to overlap GCN4 by 130 nucleotides, we provide strong evidence that
      those ribosomes which translate GCN4 do so by ignoring the uORF4 AUG start codon.
      This conclusion is in accord with the fact that translation of a uORF4-lacZ
      fusion was lower in a derepressed gcd1 mutant than in a nonderepressible gcn2
      strain. We also show that increasing the distance between uORF1 and uORF4 to the
      wild-type spacing that separates uORF1 from GCN4 specifically impaired the
      ability of uORF1 to derepress GCN4 translation. As expected, this alteration led
      to increased uORF4-lacZ translation in gcd1 cells. Our results suggest that under
      starvation conditions, a substantial fraction of ribosomes that translate uORF1
      fail to reassemble the factors needed for reinitiation by the time they scan to
      uORF4, but become competent to reinitiate after scanning the additional sequences
      to GCN4. Under nonstarvation conditions, ribosomes would recover more rapidly
      from uORF1 translation, causing them all to reinitiate at uORF4 rather than at
      GCN4.

PMID- 1986243
TI  - An intact histone 3'-processing site is required for transcription termination in
      a mouse histone H2a gene.
AB  - A transcription termination site has been characterized between the mouse histone
      H2a-614 and H3-614 genes. There is a poly(A)- RNA present in small amounts in the
      nucleus which ends 600 nucleotides 3' to the H2a-614 gene. Nuclear transcription
      studies demonstrate that transcription extends at least 600 nucleotides 3' to the
      gene but is greatly reduced 700 nucleotides 3' to the gene. If all or part of the
      normal 3'-processing signal, consisting of the stem-loop and the U7 small nuclear
      ribonucleoprotein binding site, is deleted, transcription then continues past the
      putative termination site and RNAs which end at the 3' end of the downstream H3
      614 gene accumulate. Insertion of a 150-nucleotide fragment containing the
      termination site between the histone 3' end and downstream polyadenylation sites
      reduces usage of polyadenylation sites 85 to 90%. Taken together these results
      suggest there is a transcription termination site which requires an intact
      histone 3'-processing signal to function.

PMID- 1986244
TI  - Peroxisomes in Saccharomyces cerevisiae: immunofluorescence analysis and import
      of catalase A into isolated peroxisomes.
AB  - To isolate peroxisomes from Saccharomyces cerevisiae of a quality sufficient for
      in vitro import studies, we optimized the conditions for cell growth and for cell
      fractionation. Stability of the isolated peroxisomes was monitored by catalase
      latency and sedimentability of marker enzymes. It was improved by (i) using cells
      that were shifted to oleic acid medium after growth to stationary phase in
      glucose precultures, (ii) shifting the pH from 7.2 to 6.0 during cell
      fractionation, and (iii) carrying out equilibrium density centrifugation with
      Nycodenz containing 0.25 M sucrose throughout the gradient. A concentrated
      peroxisomal fraction was used for in vitro import of catalase A. After 2 h of
      incubation, 62% of the catalase was associated with, and 16% was imported into,
      the organelle in a protease-resistant fashion. We introduced immunofluorescence
      microscopy for S. cerevisiae peroxisomes, using antibodies against thiolase,
      which allowed us to identify even the extremely small organelles in glucose-grown
      cells. Peroxisomes from media containing oleic acid were larger in size, were
      greater in number, and had a more intense fluorescence signal. The peroxisomes
      were located, sometimes in clusters, in the cell periphery, often immediately
      adjacent to the plasma membrane. Systematic immunofluorescence observations of
      glucose-grown S. cerevisiae demonstrated that all such cells contained at least
      one and usually several very small peroxisomes despite the glucose repression.
      This finding fits a central prediction of our model of peroxisome biogenesis:
      peroxisomes form by division of preexisting peroxisomes; therefore, every cell
      must have at least one peroxisome if additional organelles are to be induced in
      that cell.

PMID- 1986246
TI  - Aspergillus nidulans wetA activates spore-specific gene expression.
AB  - The Aspergillus nidulans wetA gene is required for synthesis of cell wall layers
      that make asexual spores (conidia) impermeable. In wetA mutant strains, conidia
      take up water and autolyze rather than undergoing the final stages of maturation.
      wetA is activated during conidiogenesis by sequential expression of the brlA and
      abaA regulatory genes. To determine whether wetA regulates expression of other
      sporulation-specific genes, its coding region was fused to a nutritionally
      regulated promoter that permits gene activation in vegetative cells (hyphae)
      under conditions that suppress conidiation. Expression of wetA in hyphae
      inhibited growth and caused excessive branching. It did not lead to activation of
      brlA or abaA but did cause accumulation of transcripts from genes that are
      normally expressed specifically during the late stages of conidiation and whose
      mRNAs are stored in mature spores. Thus, wetA directly or indirectly regulates
      expression of some spore-specific genes. At least one gene (wA), whose mRNA does
      not occur in spores but rather accumulates in the sporogenous phialide cells, was
      activated by wetA, suggesting that wetA may have a regulatory function in these
      cells as well as in spores. We propose that wetA is responsible for activating a
      set of genes whose products make up the final two conidial wall layers or direct
      their assembly and through this activity is responsible for acquisition of spore
      dormancy.

PMID- 1986245
TI  - Changes in the stability of a human H3 histone mRNA during the HeLa cell cycle.
AB  - A major component of the regulation of histone protein synthesis during the cell
      cycle is the modulation of the half-life of histone mRNA. We have uncoupled
      transcriptional and posttranscriptional regulation by using a Drosophila hsp70
      human H3 histone fusion gene that produces a marked human H3 histone mRNA upon
      heat induction. Transcription of this gene can be switched on and off by raising
      and lowering cell culture temperatures, respectively. HeLa cell lines containing
      stably integrated copies of the fusion gene were synchronized by double thymidine
      block. Distinct populations of H3 histone mRNA were produced by heat induction in
      early S-phase, late S-phase, or G2-phase cells, and the stability of the induced
      H3 histone mRNA was measured. The H3 histone mRNA induced during early S phase
      decayed with a half-life of 110 min, whereas the same transcript induced during
      late S phase had a half-life of 10 to 15 min. The H3 histone mRNA induced in non
      S-phase cells is more stable than that induced in late S phase, with a half-life
      of 40 min. Thus, the stability of histone mRNA is actively regulated throughout
      the cell cycle. Our results are consistent with an autoregulatory model in which
      the stability of histone mRNA is determined by the level of free histone protein
      in the cytoplasm.

PMID- 1986247
TI  - Proline-independent binding of PUT3 transcriptional activator protein detected by
      footprinting in vivo.
AB  - The PUT3 gene product is a transcriptional activator required for expression of
      the enzymes of the proline utilization pathway. Using two methods of footprinting
      in vivo, we have determined that PUT3 protein is poised at the promoters of the
      genes encoding these enzymes and that proline-mediated induction modulates the
      activity of constitutively bound PUT3.

PMID- 1986248
TI  - STY, a tyrosine-phosphorylating enzyme with sequence homology to serine/threonine
      kinases.
AB  - We have cloned a novel kinase (STY) from an embryonal carcinoma cell line.
      Sequence analysis of the STY cDNA reveals that it shares sequence homology with
      serine/threonine-type kinases and yet the bacterial expression product of the STY
      cDNA appears to have serine-, threonine-, and tyrosine-phosphorylating
      activities. The predicted STY protein is highly basic and contains a putative
      nuclear localization signal. During differentiation, two new mRNAs were detected
      in addition to the embryonic transcript.

PMID- 1986249
TI  - Alternative initiation of translation determines cytoplasmic or nuclear
      localization of basic fibroblast growth factor.
AB  - Three forms of basic fibroblast growth factor (bFGF), initiated at an AUG (18
      kDa) and two CUG (21 and 22.5 kDa) start codons, were produced following
      transfection of COS cells with human hepatoma bFGF cDNA. The subcellular
      localization of the different forms was investigated directly or by using
      chimeric genes constructed by fusion of the bFGF and chloramphenicol
      acetyltransferase open reading frames. The AUG-initiated proteins were
      cytoplasmic, while the CUG-initiated forms were nuclear. The signal sequence
      responsible for the nuclear localization of bFGF is contained within 37 amino
      acid residues between the second CUG and the AUG start codons. Alternative
      initiation of translation regulates the subcellular localization of bFGF and thus
      could modulate its role in cell growth and differentiation control.

PMID- 1986250
TI  - The same CCAAT box-binding factor binds to the promoter of two coordinately
      regulated major histocompatibility complex class II genes.
AB  - Using competition mobility shift, methylation interference, and proteolytic
      clipping DNA binding assays, we demonstrate that the protein binding the major
      histocompatibility complex A beta CCAAT box is indistinguishable from the protein
      previously named NF-Y, which binds the major histocompatibility complex E alpha
      CCAAT box. Although the two CCAAT boxes share the same 10-base core sequence,
      termed the Y box, their flanking sequences, known to be important for binding,
      are very different.

PMID- 1986251
TI  - Induction of growth arrest by a temperature-sensitive p53 mutant is correlated
      with increased nuclear localization and decreased stability of the protein.
AB  - A temperature-sensitive mutant of p53, p53Val-135, was found to be able to arrest
      cell proliferation when overexpressed at 32.5 degrees C. While much of the
      protein was cytoplasmic in cells proliferating at 37.5 degrees C, it became
      predominantly nuclear at 32.5 degrees C. Concomitantly, p53Val-135 became
      destabilized, although not to the extent seen in primary fibroblasts.

PMID- 1986252
TI  - Heat shock-induced interactions of heat shock transcription factor and the human
      hsp70 promoter examined by in vivo footprinting.
AB  - Genomic footprinting of the human hsp70 promoter reveals that heat shock induces
      a rapid binding of a factor, presumably heat shock transcription factor, to a
      region encompassing five contiguous NGAAN sequences, three perfect and two
      imperfect matches to the consensus sequence. Arrays of inverted NGAAN sequences
      have been defined as the heat shock element. No protein is bound to the heat
      shock element prior to or after recovery from heat shock. Heat shock does not
      perturb the binding of factors to other regulatory elements in the promoter which
      contribute to basal expression of the hsp70 gene.

PMID- 1986254
TI  - Positive and negative regulation of immunoglobulin gene expression by a novel B
      cell-specific enhancer element.
AB  - A new B-cell-specific enhancer element has been identified 3' of E4 and the
      octamerlike motifs in the human immunoglobulin heavy-chain gene enhancer. Tandem
      copies of this 67-bp MnlI-AluI fragment, when fused to the chloramphenicol
      acetyltransferase gene driven by the conalbumin promoter, stimulated
      transcription in B cells but not in Jurkat T cells or HeLa cells. Footprinting
      analysis revealed that the identical sequence CCGAAACTGAAAAGG, designated E6, was
      protected by nuclear extracts from B cells, T cells, or HeLa cells. Gel mobility
      shift assays using a synthetic E6 motif detected a B-cell-specific complex in
      addition to a ubiquitous band found also in T cells and HeLa cells. In agreement
      with the results of gel retardation assays, tandem copies of the E6 motif
      stimulated transcription in ARH77 and Raji cells but not in Jurkat or HeLa cells.
      Furthermore, a mutant E6 motif lost both in vitro binding activity and in vivo
      enhancer activity. In striking contrast to the mouse Ig heavy-chain enhancer, in
      which the octamer motif acts as a B-cell-specific enhancer element, the human
      enhancer contains an octamerlike sequence with one base substitution which bound
      octamer-binding proteins with only very low affinity and showed no enhancer
      activity of its own. Interestingly, the MnlI-AluI fragment could suppress the
      basal-level activity of the conalbumin promoter in both Jurkat and HeLa cells.
      Moreover, simian virus 40 enhancer activity was blocked by the MnlI-AluI fragment
      in HeLa cells but not in B cells. Thus, the novel enhancer element identified in
      this study is probably a target site for both positive and negative factors.

PMID- 1986253
TI  - Two distinct domains in the yeast transcription factor IID and evidence for a
      TATA box-induced conformational change.
AB  - Transcription factor IID from Saccharomyces cerevisiae (YIID) binds the TATA box
      element present in most RNA polymerase II promoters. In this work, partial
      proteolysis was used as a biochemical probe of YIID structure. YIID consists of a
      protease-sensitive amino terminus and a highly stable, protease-resistant carboxy
      terminal core. The cleavage sites of the predominant chymotrypsin- and trypsin
      derived fragments were mapped to amino acid residues 40 to 41 and 48 to 49,
      respectively, by amino-terminal peptide sequencing. Removal of the amino terminus
      resulted in a dramatic increase in the ability of YIID to form a stable complex
      with DNA during gel electrophoresis mobility shift assays and a two- to fourfold
      increase in DNA-binding affinity, as assayed by DNase I footprinting analysis.
      The carboxy-terminal 190-amino-acid core was competent for transcription in vitro
      and was similar in activity to native YIID. DNA containing a TATA element induced
      hypersensitive sites in the amino-terminal domain and stabilized the core domain
      to further proteolytic attack. Native YIID did not bind to a TATA box at 0
      degrees C, whereas the carboxy-terminal DNA-binding domain did. These results
      suggest that YIID undergoes a conformational change upon binding to a TATA box.
      Southern blotting showed that the carboxy-terminal domain is highly conserved,
      while the amino-terminal domain diverged rapidly in evolution, even between
      closely related budding yeasts.

PMID- 1986256
TI  - Caffeine-induced reduction of the survival of gamma-irradiated HeLa cells and the
      reversal of the caffeine effect by Escherichia coli RecA protein.
AB  - It is confirmed that survival of gamma-irradiated HeLa cells is decreased by post
      treatment with caffeine. The caffeine effect is believed to be the result of an
      inhibition of the repair of gamma-ray-induced DNA damage. In this work we show
      that the caffeine-induced reduction of the survival of gamma-irradiated HeLa
      cells is reversed when Escherichia coli RecA protein is introduced into the cells
      with the aid of liposomes.

PMID- 1986257
TI  - Organotin compounds induce aneuploidy in human peripheral lymphocytes in vitro.
AB  - In vitro exposure of PHA-stimulated human lymphocytes to organotin compounds
      resulted in statistically significant increases in the frequencies of
      hyperdiploid cells. When taken together with our previous study demonstrating
      spindle inhibiting effects of the same organotin compounds by an indirect method
      (Jensen et al., 1989), the present study strongly indicates that organotin
      compounds are able to induce aneuploidy, probably by affecting spindle function.

PMID- 1986255
TI  - Characterization of the mouse transforming growth factor-beta 1 promoter and
      activation by the Ha-ras oncogene.
AB  - We have cloned and sequenced a mouse genomic transforming growth factor beta 1
      (TGF-beta 1) DNA fragment that includes the 5' untranslated and regulatory
      regions of the gene. High-sequence homology with the human TGF-beta 1 gene (66%
      nucleotide identity in 2.7 kb of DNA upstream of the translational start site)
      suggested evolutionary conservation of transcriptional regulation for TGF-beta 1.
      The absence of TATA or CAAT box sequences but the presence of several Sp1-binding
      and AP-2-like sequences in the promoter region was noted, as previously reported
      for the human gene. Two transcriptional initiation sites separated by 290 bp were
      identified by S1 nuclease analysis; these corresponded to transcripts with 866
      and 576 nucleotides of 5' untranslated leader sequence. S1 analysis of different
      mouse tissues indicated that the two transcripts were present in the same ratio
      even though the total level of TGF-beta 1 mRNA transcripts varied between
      tissues. Promoter activity adjacent to both transcriptional start sites was
      demonstrated by using chloramphenicol acetyltransferase fusion genes assayed in
      mouse AKR-2B fibroblast cells. Transcriptional activation of the promoter by the
      Ha-ras oncogene was also demonstrated. The minimal promoter constructs (113 and
      104 bp 5' of the first and second transcriptional start sites, respectively) were
      sufficient for induction by Ha-ras. These studies characterize the 5' structure
      and basal promoter activity of the mouse TGF-beta 1 gene as well as the
      transcriptional activation of TGF-beta 1 by the Ha-ras oncogene.

PMID- 1986258
TI  - Diverse backmutations at an ochre defect in the tyrA gene sequence of E. coli
      B/r.
AB  - A DNA fragment including most of the tyrA gene from E. coli B/r strain WU (Tyr-,
      Leu-) was amplified in vitro by polymerase chain reaction. The sequence was
      determined, first, for essentially all of the fragment to locate an ochre
      nonsense defect, and second, repeatedly for a region of the fragment from several
      independent isolates containing backmutations at the ochre codon (spontaneous and
      UV-induced). There were 20 single base differences in the tyrA gene region from
      the analogous wild-type E. coli K12 sequence: an ochre codon at amino acid
      position 161, 18 silent changes (1 at the first codon base and 17 at the third)
      and one replacement of valine by alanine. Different backmutations at the ochre
      codon encoded lysine, glutamine, glutamic acid, leucine, cysteine, phenylalanine,
      serine or tyrosine. The diversities of base substitutions at the ochre codon
      after UV mutagenesis or after mutagenesis where targeting by dimers was reduced
      or eliminated (after photoreversal of irradiated cells treated with nalidixic
      acid to induce SOS functions or after UV mutagenesis of cells containing
      amplified DNA photolyase) were similar (with two notable exceptions). The overall
      differences between the gene sequences for E. coli K12 or B/r seemed consistent
      with the neutral theory of molecular evolution.

PMID- 1986259
TI  - Nucleotide pools and mutagenic effects of alkylating agents in wild-type and APRT
      deficient Friend erythroleukaemia cells.
AB  - Wild-type Friend mouse erythroleukaemia cells (clone 707) were compared with
      adenine phosphoribosyltransferase (APRT)-deficient mutant subclones (707DAP8 and
      707DAP10) for sensitivity to cell killing and mutagenesis by ethyl
      methanesulphonate (EMS) and methyl methanesulphonate (MMS). Cells were exposed to
      0-300 micrograms/ml EMS and to 0-20 micrograms/ml MMS for a period of 16 h. A
      slight difference was found between wild-type cells and the two APRT-deficient
      subclones in terms of sensitivity to cell killing by both mutagens. The APRT
      deficient subclones were, however, significantly more sensitive than wild-type
      cells to mutagenesis to 5-bromo-2-deoxyuridine resistance and 6-thioguanine
      resistance by EMS and MMS. The APRT-deficient subclones were found to have
      significantly decreased levels of dATP and dTTP nucleotides and decreased levels
      of all four ribonucleoside triphosphates (ATP, GTP, CTP and UTP) relative to wild
      type cells. Wild-type Friend cells were found to have insignificant levels O6
      methylguanine-DNA methyl transferase and it is suggested that the increased
      mutagen sensitivity of APRT-deficient cells may be due to imbalance of
      deoxyribonucleoside triphosphate pools during DNA excision-repair processes, or
      more probably due to deficiency of ATP for ATP-dependent DNA excision-repair
      enzymes.

PMID- 1986260
TI  - Lipid peroxidation and benzo[a]pyrene activation to mutagenic metabolites: in
      vivo influence of vitamins A, E and C and glutathione in both dietary vitamin A
      sufficiency and deficiency.
AB  - Rats fed with either a sufficient-vitamin A or a vitamin A-free diet were
      pretreated with 750 mg/kg body weight of retinyl palmitate, alpha-tocopherol
      acetate, ascorbic acid or glutathione. Benzo[a]pyrene (BaP) metabolism and BaP
      induced mutagenesis in Salmonella typhimurium TA98 were investigated and related
      to lipid peroxidation activities in postmitochondrial (S9) liver fraction. The
      microsomal mixed-function oxidase activities were decreased by vitamin A
      deficiency and weakly affected by scavenger treatment. The rate of lipid
      peroxidation of microsomal membranes was unaffected by vitamin A deficiency
      because of decreased polyunsaturated fatty acids and increased vitamin E
      contents. However, lipid peroxidation was decreased by pretreatment with fat
      soluble vitamins (chiefly vitamin E) and increased by ascorbic acid. Within each
      experimental group both BaP metabolism and BaP mutagenic activity were closely
      correlated with the rate of lipid peroxidation. In vitamin A deficiency, the
      increased BaP metabolism and mutagenicity could be related to a decrease in
      cytosolic contents of scavengers (vitamin A and glutathione). In Ames test
      conditions, the free radical pathway became a route for BaP metabolism and thus
      the BaP activation to mutagenic metabolites is related to the cellular status in
      free radical scavengers.

PMID- 1986262
TI  - Adaptive response to chromosome damage in cultured human lymphocytes primed with
      low doses of X-rays.
AB  - Human lymphocytes exposed to 0.02 Gy of X-rays in the G1 but not the G0 phase
      became less susceptible to the induction of chromosome aberrations of the
      chromosome type by subsequent exposure to 3 Gy of X-rays. The induction of
      chromatid-type aberrations was not affected by the pretreatment with the priming
      dose. The expression of this adaptive-type response was transitory, being maximum
      at 5 h, and disappeared at 9 h after the initial low-dose exposure. Cell-cycle
      analysis excluded the possibility of a spurious consequence of differential cell
      cycle progression.

PMID- 1986261
TI  - Loss of heterocyclic amine mutagens by insoluble hemicellulose fiber and high
      molecular-weight soluble polyphenolics of coffee.
AB  - The presence of 2 kinds of components in brewed and instant coffee that could
      remove and destroy heterocyclic amine mutagens was demonstrated. The component
      that could remove the mutagens was insoluble fiber composed of hemicellulose. The
      fiber could tightly adsorb the mutagens Trp-P-1, Trp-P-2, Glu-P-1 and A alpha C,
      and those generated in roasted coffee beans. The component that could destroy the
      mutagens was high-molecular-weight soluble polyphenolics. They might be converted
      into quinone derivatives in the presence of molecular oxygen. The quinone
      derivatives might destroy the mutagens. The fibers and the polyphenolics in one
      cup of brewed or instant coffee had the capacity to remove and destroy a
      substantial amount of the mutagens in pyrolysates of foodstuffs.

PMID- 1986263
TI  - Comparison of initial yields of DNA-to-protein crosslinks and single-strand
      breaks induced in cultured human cells by far- and near-ultraviolet light, blue
      light and X-rays.
AB  - The initial yields of DNA-to-protein crosslinks (dpc) caused by ionizing and
      nonionizing radiations were compared, with emphasis upon values within the
      biological dose ranges (D0). Induction of dpc in cold (0-0.5 degrees C) human P3
      teratocarcinoma cells was measured by using alkaline elution techniques after
      exposure to monochromatic UVC (254 nm), UVB (313 nm), UVA (365 and 405 nm), and
      blue light (434 nm). UVC and UVB light induced detectable numbers (about 100 dpc
      per cell per D0). Monochromatic UVA radiations produced yields about 8 times
      higher than UVC or UVB (for 365 nm, about 1500 dpc per cell per D0) Similar
      results at low doses were obtained for measurements of single-strand breaks
      induced by the different radiations. The action spectra for dpc were closely
      similar. The biological significance of these relatively high numbers of DNA
      lesions caused by environmental nonionizing radiation that readily penetrates
      into human skin is not understood.

PMID- 1986264
TI  - Induction of sister-chromatid exchanges (SCE), polyploidy, and micronuclei by
      plant flavonoids in human lymphocyte cultures. A comparative study of 19
      flavonoids.
AB  - Nineteen naturally occurring flavonoids were studied with regard to their SCE
      inducing potency and their capability of inducing polyploidy and micronuclei in
      human lymphocyte cultures. The cells were treated for a period of 48 h. The
      flavone C-glycosides, vitexin and orientin, exhibited a moderate SCE-inducing
      activity, whereas the other compounds displayed only weak effects or were
      inactive. Polyploidy was induced by procyanidins consisting of 3 or 4 flavanol
      units and to a lesser extent by flavone, flavonol, and anthocyanidin aglycones.
      The aglycones as well as the C-glycosides and the O-glycosides, spiraeoside and
      luteolin-7-glucoside, were more or less active in inducing micronuclei in the
      lymphocytes. The flavonol O-glycosides, rutin and hyperoside, and the monomeric
      and dimeric flavanols failed to produce any genotoxic effects. The results are
      discussed with respect to a possible structure-activity relationship.

PMID- 1986265
TI  - Induction of chromosomal aberrations in the CHO mutant EM9 and its parental line
      AA8 by EcoRI restriction endonuclease: electroporation experiments.
AB  - EcoRI restriction endonuclease (RE), which produces cohesive-ended double-strand
      breaks (dsb) in DNA, was tested in the ethyl methanesulfonate- and X-ray
      sensitive CHO mutant EM9 and its parental cell strain AA8 for its chromosomal
      aberration-inducing effect. The RE was efficiently introduced by electroporation
      into AA8 cells, while the mutant cells showed a very high sensitivity to
      electroporation, which consistently resulted in cell death. Nevertheless, the
      incubation of EM9 cells in the presence of EcoRI, without electroporation, was
      sufficient to induce about three times the chromosome damage observed in the
      electroporated parental cell line AA8 for any given dose of the RE.

PMID- 1986266
TI  - Female-specific mutagenic response of mice to hycanthone.
AB  - Male and female gametogeneses differ markedly in all mammals. While male germ
      cells are continuously being produced from stem cells throughout the reproductive
      life span, the number of female germ cells is fixed during prenatal development
      and, soon after birth, all of the oocytes are arrested in a modified diplotene,
      or dictyate, stage. Following puberty, dictyate oocytes are hormonally triggered
      to mature either singly or in groups, resulting in ovulation and the completion
      of the first meiotic division. It has been hypothesized that female mice are more
      susceptible to dominant lethal effects of intercalating agents than male mice
      because oocyte chromosomes, which are arrested in a diffuse state, are generally
      more accessable to intercalation than are the more condensed chromosomes present
      within most male germ cell stages. This hypothesis was further tested using the
      intercalating agent hycanthone methane-sulfonate. Effects of hycanthone were
      studied in maturing and primordial oocytes and in male germ cells throughout
      spermatogenesis. No induction of dominant lethality was observed for treated
      males while a significant increase in embryonic death, expressed around the time
      of implantation, was observed in females that mated within 4.5 days after
      treatment. These effects were the result of dominant lethal mutations induced in
      maturing oocytes and not of maternal toxicity as indicated by the presence of
      chromosomal aberrations observed at first-cleavage metaphase of zygotes obtained
      from treated females. These results add support to the hypothesis that certain
      intercalating chemicals, which are not mutagenic to male mice, may be mutagenic
      to females and point to a need for more in-depth studies of female-specific
      mutagenesis.

PMID- 1986267
TI  - Structure-activity relationships of aromatic amines in the Ames Salmonella
      typhimurium assay.
AB  - The author tried in a somewhat limited work to quantitatively correlate the
      electronic and steric intramolecular interactions of substituents on the amino
      group (influencing the enzymatic reactions of aromatic amines) and the mutagenic
      event. It was assumed that there is a correlation between these
      biotransformations and the electronic state of aromatic amines at the ionic
      dissociation equilibrium. The approach is rather empirical and arbitrary but the
      overall agreement between experimental mutagenic potencies and the values
      calculated was encouraging and led the author to further developments. It is
      hoped that the concepts used in this work may be applied to other aromatic
      molecules bearing an amino group.

PMID- 1986268
TI  - Occurrence of sister-chromatid exchange and chromosomal aberration during vitamin
      A-induced cell differentiation in vitro.
AB  - Prompted by the recent growth in interest in the mechanisms of vitamin A (VA)
      action, we studied the effects of VA on the frequency of sister-chromatid
      exchange (SCE) and chromosome aberration (CA) in a culture system using a fetal
      Syrian hamster (female) pulmonary epithelial cell line (M3E3/C3). When
      manipulated by specific culture conditions, the cells in this system could be
      rendered competent for activation of polycyclic aromatic hydrocarbons. Cells
      induced to such a state were exposed to 0, 2, 8 and 24 micrograms/ml of VA for 4
      days. The average frequency of SCE per metaphase increased from 1.64 at 0
      micrograms/ml to 3.44 at 24 micrograms/ml with a moderate degree of dose
      dependence. In addition, the q-terminal area of X-chromosomes appears to be one
      of the most specifically vulnerable sites for SCE due to VA. The frequency of CA
      encompassing triradial, quadriradial, quinqueradial, ring and dicentric
      chromosomes also increased in a rather sigmoid fashion from 3.6% at 0
      micrograms/ml to 14.8% at 24 micrograms/ml. Apart from the frequently
      demonstrated protective roles or otherwise less often encountered promotional
      effects of VA in the development of squamous metaplasia, neoplasia, neoplastic
      transformation or mutation, an alternative interpretation for the current results
      implies a possible relationship between SCE and CA caused by VA and cell
      differentiation and/or drug resistance mechanisms.

PMID- 1986269
TI  - Specificities mediated by neighboring nucleotides appear to underlie mutation
      induced by antifolates in E. coli.
AB  - The antifolate, trimethoprim (TRMP, 5 microM) caused a 10-fold increase in
      mutation frequency and primarily induced base substitution and deletion mutations
      in wild-type E. coli. Base-substitutions induced by antifolates were equally
      divided between transition and transversion mutations. When mutations consistent
      with expected antifolate-induced deoxynucleotide pool imbalances were considered,
      29 out of 32 base-substitution mutations in the i-d region of the lacI gene were
      followed 3' by the same nucleotide substituted at the base mismatch site and all
      but one mutation occurred at sites consistent with next nucleotide effects
      resulting from antifolate-induced deoxynucleotide pool alterations. 66% of the
      TRMP-induced base-substitutions were also found at sites of frequent mutation
      identified in the spontaneous spectrum of a mutator D5 strain of E. coli which is
      deficient in the 3'-exonucleolytic proofreading function of DNA polymerase III
      holoenzyme. These results suggest that the pool imbalances induced by the
      antifolate trimethoprim compromise the proofreading activity of polymerase III
      holoenzyme and lead to mutation at specific sites. The results also imply that
      not all DNA sequence environments encountered by DNA polymerase III holoenzyme
      and its accompanying exonuclease are handled with equal facility at the level of
      nucleotide insertion and exonucleolytic proofreading when the enzyme is faced
      with an intracellular nucleotide pool imbalance. A number of small deletion and
      duplication mutations were also induced by the antifolate trimethoprim. In most
      cases these mutations were flanked by at least two A:T base pairs which could
      facilitate DNA-strand breakage at deoxyuridine misincorporation sites.

PMID- 1986270
TI  - Mutagenicity and antimutagenicity of air-borne particulates.
AB  - A methanol extract of air-borne particulates collected in a suburban area of
      Okayama City showed not only mutagenicity but also antimutagenicity in the Ames
      test. Thus, when the mutagenicity of this preparation in Salmonella typhimurium
      TA98 (with metabolic activation) was measured, we observed that the dose response
      reached a plateau at 27 m3 air equivalent of the particulate, showing
      approximately equal numbers of revertants in the dose range 27-270 m3 equivalent.
      This plateau formation was not seen in the dose response of a blue-cotton extract
      of this preparation: the extract gave a linearly increasing dose response up to
      270 m3 equivalent. This finding suggests that some factors that inhibit the
      mutagenicity were present in this methanol extract and that these inhibitors were
      not adsorbable to blue cotton, an adsorbent selective for compounds having 3 or
      more fused rings. From the portion unadsorbed to blue cotton, we isolated the
      antimutagenic factors and identified them as long-chain fatty acids: palmitic,
      stearic, oleic and linoleic acids. Analysis of several samples, including those
      from other parts of Japan, has suggested that these antimutagenic fatty acids are
      ubiquitous in air-borne particulates.

PMID- 1986271
TI  - An endonuclease activity of Escherichia coli that specifically removes 8
      hydroxyguanine residues from DNA.
AB  - An enzyme that specifically removes an 8-hydroxyguanine (8-OH-Gua) residue in DNA
      has been purified from Escherichia coli. To assay the enzymatic activity, a
      synthetic double-stranded DNA (dsDNA) containing 8-OH-Gua at a defined position
      was used as a substrate. The substrate DNA was simultaneously cleaved at 2 sites,
      i.e., the phosphodiester bonds 5' and 3' to 8-OH-Gua, leaving a phosphate at each
      of the neighboring deoxynucleosides. The cleavage was observed only in dsDNA, but
      not with single-stranded DNA containing 8-OH-Gua. This enzyme showed almost no
      activity on DNAs containing other kinds of modified bases such as 8
      hydroxyadenine, O6-methylguanine and N7-methylguanine. Also DNAs containing
      mismatches (A/G or C/T) were not cleaved. Studies on several other properties of
      this enzyme indicate that it differs from endonucleases previously isolated from
      E. coli, indicating that it is likely to be an endonuclease which specifically
      recognizes 8-OH-Gua in dsDNA.

PMID- 1986272
TI  - Construction of Escherichia coli K12 phr deletion and insertion mutants by gene
      replacement.
AB  - We replaced an Escherichia coli phr gene by a 1.4-kb fragment of DNA coding for
      resistance to chloramphenicol. Characterization of 2 deletions (phr-19 and phr
      36) and 1 insertion (phr-34) in the phr gene revealed no photoreactivation.
      Photoreactivation-deficient strains of either recA56 or lexA1(ind-) were more
      sensitive to UV radiation in the dark than phr-proficient counterparts. The
      presence of the phr defect in uvrA6 strains increased by 1.5-2-fold his-4(Ochre)
      to His+ mutation induced by ultraviolet light compared to uvrA6 phr+ strains,
      although there was no difference in UV sensitivity between uvrA6 phr+ and uvrA6
      phr- strains. 30-35% of the His+ mutations thus induced were suppressor mutations
      in uvrA6 phr+ and 49-55% in uvrA6 phr- strains. The UV mutagenesis results are
      consistent with the previous observations that suppressor mutations targeted by a
      thymine-cytosine pyrimidine dimer are reduced in the dark in cells with amplified
      DNA photolyase.

PMID- 1986273
TI  - Roles of two types of O6-methylguanine-DNA methyltransferases in DNA repair.
AB  - Escherichia coli possesses 2 types of O6-methylguanine-DNA methyltransferases,
      one inducible and the other constitutive. These enzymes are coded by the ada and
      the ogt genes, respectively. Using a synthetic ogt-specific probe, we mapped ogt
      at 29.4 min, near the 5'-flanking region of the nirR gene, on the E. coli
      chromosome. To elucidate the roles of the 2 types of methyltransferases in DNA
      repair, we constructed mutant strains which lack either one or both of the genes.
      In either the ada+ or the ada- background, the ogt mutation had no effect on cell
      survival after N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) treatment. On the
      other hand, ada- ogt- cells were more prone to mutation as compared to the ada-
      ogt+ cells exposed to MNNG. The frequency of spontaneous mutation of cells
      defective in either one or both of the genes was the same, however, the
      introduction of the ogt+ plasmid into the cells produced a 2-3-fold decrease in
      the frequency of spontaneous mutation. O6-Methylguanine-DNA methyltransferases
      appear to eliminate premutagenic DNA lesions not only from cells exposed to
      alkylating agents but also from those grown in the absence of the agents.

PMID- 1986274
TI  - Mutagenicity of Maillard reaction products from D-glucose-amino acid mixtures and
      possible roles of active oxygens in the mutagenicity.
AB  - The mutagenicity for Salmonella typhimurium TA100 without S9 mix of Maillard
      reaction products (MRP) obtained from equimolar amounts of glucose and amino
      acids under different pHs was investigated. MRP derived from arginine and lysine
      exhibited the strongest mutagenicity, and weaker mutagenicity was shown by the
      mixtures with alanine, serine, threonine and monosodium glutamate. MRP from
      proline and cysteine had no detectable mutagenicity. Furthermore, glucose
      arginine and glucose-lysine reaction mixtures, which presented a marked
      mutagenicity, showed pH- and browning intensity-dependent expression of their
      mutagenic activities. The mutagenicity of MRP, especially glucose-arginine and
      glucose-lysine mixtures, was significantly suppressed by active oxygen scavengers
      such as cysteine, mannitol, alpha-tocopherol, catalase and superoxide dismutase
      (SOD) and reducing agents such as sodium bisulfite and glutathione. Among these
      desmutagenic factors tested, cysteine, catalase, sodium bisulfite and glutathione
      had higher desmutagenic activities than the others. Accordingly, it is assumed
      that the mutagenicity of MRP is due to the direct action of low-molecular-weight
      compounds such as carbonyls and heterocyclics produced by the Maillard reaction
      and is enhanced by active oxygens, especially singlet oxygen and hydrogen
      peroxide derived from their autoxidation.

PMID- 1986275
TI  - A mechanism for relief of replication blocks by activation of unused origins and
      age-dependent change in the caffeine susceptibility in xeroderma pigmentosum
      variant.
AB  - The first XP16KO-I (age 42 without cancer) and the second XP16KO-II (age 52 after
      carcinogenesis) skin fibroblasts of a xeroderma pigmentosum variant (XPV) were
      studied. First, caffeine had no effect on XP16KO-I cells, but it potentiated UV
      killing and inhibited the recovery of DNA synthesis and the elongation of nascent
      DNA after UV irradiation in XP16KO-II cells, indicating an age-dependent change
      from caffeine resistance to sensitivity. These results confirmed a previous
      similar change in an unrelated XPV subject and the existence of 2 XPV subgroups,
      caffeine-sensitive and -resistant. Further, processing of post-excision breaks
      was also slightly more defective in XP16KO-II than in XP16KO-I cells. Second,
      nascent DNA pulse-labeled at 1.5 h after 5 J/m2 indicated an initial complete
      blockage of elongation by each dimer in XP16KO-II cells and less complete blocks
      in XP16KO-I and normal cells. The nascent DNA in 5 J/m2-irradiated XP16KO-II
      cells was 4 microns (8 x 10(6) Da) long for the peak fraction, with a possible
      range up to 20 microns of average replicon size, indicating activation of at
      least 4 microns-spaced new origins around 1.5 h post irradiation. Post-labeling
      chase without caffeine allowed nearly normal elongation to the present maximum
      molecular weight of 2.60-2.80 x 10(8) in 3-4 h in irradiated XP16KO-I and -II
      cells. Thus, the activation of unused origins at shorter spaces is a main
      mechanism for relief and the reduction of almost all unreplicated regions or
      blocks initially formed by 2 dimers in trans on both leading strands between
      converging forks. Post-labeling addition of 1 mM caffeine increased perpetuated
      blocks to a frequency of about 10% of the initial number of dimers in 4 h in
      XP16KO-II cells, but not in XP16KO-I and normal cells.

PMID- 1986276
TI  - The role of DNA repair in resistance of L1210 cells to isomeric 1,2
      diaminocyclohexaneplatinum complexes and ultraviolet irradiation.
AB  - Resistance to cisplatin in several murine leukemia L1210 cell lines is due to
      enhanced DNA repair. Other platinum complexes, particularly those containing 1,2
      diaminocyclohexane (DACH) are of interest as they effectively kill both sensitive
      (L1210/0) and cisplatin-resistant (L1210/DDP) cell lines. An L1210/DACH cell line
      has been developed that is preferentially resistant to DACH-Pt complexes. In the
      current experiments, we investigated the role that DNA repair has in resistance
      to DACH-Pt compounds. The DACH ligand exists in 3 isomeric forms which exhibit
      markedly different activities in the various resistant cell lines. Generally, R,R
      DACH-Pt was the most effective isomer. DNA repair was assayed by host-cell
      reactivation of platinated pRSVcat. DNA damage induced by all the isomeric DACH
      Pt-SO4 complexes markedly reduced CAT expression in sensitive L1210/0 cells. One
      adduct per transcribed strand of the cat gene inhibited CAT expression
      demonstrating that the sensitive cells exhibited no detectable DNA repair. All
      the resistant cell lines reactivated the plasmid DNA whether damaged with
      cisplatin or any of the 3 DACH-Pt isomers. Therefore, resistance to both
      cisplatin and DACH-Pt appears to be mediated by enhanced DNA repair, but the
      level of reactivation of the transfected plasmid did not correlate with the
      toxicity of each analogue. These results suggest that some additional event(s) is
      responsible for the substrate specificity of repair of genomic DNA. These
      resistant cell lines also exhibited resistance to UV irradiation but this was
      much less than, and did not correlate with the degree of resistance to either
      cisplatin or DACH-Pt. However, there was a good correlation between resistance to
      UV irradiation and reactivation of UV-damaged plasmid DNA. This enhanced
      reactivation suggests that enhanced repair may be the sole reason for the
      resistance to UV irradiation.

PMID- 1986277
TI  - Ultraviolet mutational spectrum in a shuttle vector propagated in xeroderma
      pigmentosum lymphoblastoid cells and fibroblasts.
AB  - In order to examine possible cell-type specificity in mutagenic events, a shuttle
      vector plasmid, pZ189, carrying a bacterial suppressor tRNA marker gene, was
      treated with ultraviolet radiation and propagated in Epstein-Barr virus
      transformed lymphoblastoid cell lines from a patient, XP12BE, with xeroderma
      pigmentosum (XP), group A, and a normal control. XP is a skin-cancer-prone
      disorder with UV hypersensitivity and defective DNA repair. Plasmid survival and
      mutations inactivating the marker gene were scored by transforming an indicator
      strain of E. coli. An earlier report on this data [Seetharam et al., (1990) J.
      Mol. Biol., 212, 433] indicated lower survival and higher mutation frequency with
      the UV-treated plasmid passed through the XP12Be(EBV) line. In the present
      report, sequence analysis of 198 mutant plasmids revealed a predominance of G:C--
      -A:T transitions with both lymphoblastoid cell lines. This finding is consistent
      with the bias of polymerases toward insertion of an adenine opposite non-coding
      photoproducts (dinucleotides or other lesions). Transversion mutagenesis, non
      adjacent double mutations, and triple-base mutations may involve other
      mechanisms. These results were compared to similar data from a fibroblast line
      from the same patient [Bredberg et al., (1986) Proc. Natl. Acad. Sci. (U.S.A.),
      83, 8273]. The frequency of G:C----A:T transitions was higher, and there were
      fewer plasmids with multiple-base substitutions and with transversion mutations
      with both XP lymphoblasts and fibroblasts than with the normal lymphoblasts and
      fibroblasts. There were no significant differences in classes or types of
      mutations in the UV-treated plasmid replicated in the XP lymphoblasts and the XP
      fibroblasts. This suggests that the major features of UV mutagenesis in different
      cell types from the same individual are similar.

PMID- 1986278
TI  - Nuclear medicine patients do not have higher mutant frequencies after exposure to
      thallium-201.
AB  - The HPRT-lymphocyte clonal assay has been used to detect mutants induced in vivo
      in humans. This method has previously detected a rise in mutant frequency among
      nuclear medicine patients following exposure to technetium-99m, at a dose
      corresponding in theory to 5.1 mGy. In the present study, nuclear medicine
      patients were sampled before and after exposure to thallium-201, corresponding to
      a whole-body dose of 4.2 mGy. No rise in mutant frequency was found. We suggest
      that a difference in the effective dose received by the patients' lymphocytes
      accounts for the apparent contradiction with earlier results.

PMID- 1986280
TI  - Replication intermediates as substrates for DNA rearrangements.
AB  - A model for the formation of DNA rearrangements in somatic cells is presented.
      Two double-strand breaks at the junctions between unreplicated DNA and newly
      replicated DNA generate four double-stranded DNA molecules that can recombine to
      form tandem duplications, inversions, deletions and extrachromosomal DNA circles.

PMID- 1986279
TI  - Sister-chromatid exchange analysis in vivo using different 5-bromo-2'
      deoxyuridine-labeling systems.
AB  - The quality of sister-chromatid differentiation, the basal rate of sister
      chromatid exchanges (SCE) and the rate of cellular proliferation were studied in
      untreated and mitomycin C(MMC)-treated mice, using 4 different systems for
      administering 5-bromodeoxyuridine (BrdU): BrdU adsorbed to charcoal, tablets of
      BrdU mixed with cholesterol, tablets of BrdU coated with agar and tablets of BrdU
      partially coated with paraffin. The quality of sister-chromatid differentiation
      with the studied methods showed a useful stain contrast in an average of 75.4%
      second-division mitosas, with the lowest average occurring in mice implanted with
      agar-coated tablets. The frequency of SCE and the replicative index were similar
      in mice administered BrdU by all 4 systems both in control and in MMC-treated
      mice. From a practical point of view, the charcoal method could be done the
      fastest.

PMID- 1986281
TI  - Role of DNA polymerase alpha and delta in radiation clastogenesis.

PMID- 1986282
TI  - A case of spontaneous trisomy in the spermatocytes of Microtus arvalis.
AB  - A triple synaptomal complex was observed between 3 small-sized chromosomes in 4
      spermatocytes closely connected by intercellular bridges, of the common vole
      (Microtus arvalis L.). Other spermatocytes from the same and from 2 other males
      had a normal chromosome complement and pairing patterns. This finding was
      interpreted as the result of a single act of non-disjunction taking place in a
      spermatogonium. These data suggest that chromosome non-disjunction in premeiotic
      germ cells can be considered one of the causes of aneuploidy in mammals.

PMID- 1986283
TI  - Effect of vitamins C and E on toxicity and mutagenicity of hexavalent chromium in
      rat and guinea pig.
AB  - The effect of simultaneous pretreatment with vitamins C and E on the toxicity and
      mutagenicity of K2Cr2O7 in rats and guinea pigs was evaluated. Dietary
      pretreatment of Cr(VI)-intoxicated rats with ascorbic acid or alpha-tocopherol
      normalized vitamin C levels in lungs but not in kidneys. The synergistic
      preventive effect of both vitamins was confirmed in the production of
      lipoperoxides in Cr(VI)-intoxicated rats. Simultaneous administration of vitamins
      C and E in guinea pigs prevented the decrease of vitamin C levels provoked by the
      oxidative effects of Cr(VI). The results of the micronucleus test in bone marrow
      showed that it was vitamin C that caused the antimutagenic effect against
      bichromate, in both rats and guinea pigs. The effect of vitamin E was
      demonstrated only in an increase of the ratio of NCE to PCE, i.e., in a decrease
      of the cytotoxic but not the mutagenic effects of hexavalent chromium.

PMID- 1986284
TI  - Study of reproductive function in persons occupationally exposed to 2,4
      dichlorophenoxyacetic acid (2,4-D).
AB  - We studied the reproductive function of 32 male farm sprayers who were exposed to
      2,4-D. Sperm analysis was made after 4 days of sexual inactivity. Parameters
      analyzed were volume, sperm count, mobility and morphology. Exposure level was
      estimated by measuring the concentration of 2,4-D in the urine. Significant
      levels of asthenospermia, necrospermia and teratospermia were found in exposed
      workers compared with unexposed controls. Over time, asthenospermia and
      necrospermia diminished but the abnormal spermatozoa (teratospermia) continued.

PMID- 1986285
TI  - Characterization of the in vitro unscheduled DNA synthesis assay in primary lung
      cells of the rat.
AB  - The in vitro unscheduled DNA synthesis (UDS) assay has been evaluated in rat
      primary lung cells with known genotoxicants. The autoradiographic method was
      employed to detect UDS in both alveolar macrophages and primary pulmonary cells.
      Data of a time course study revealed that a high radioactive labeling of DNA
      repair was achieved after a 16-h incubation with [3H]thymidine. Coupled with low
      serum (1%), hydroxyurea at the concentration of 20 mM inhibited regular DNA
      synthesis in primary lung cells in a satisfactory manner (81-88% inhibition).
      With this protocol, a dose-related increase in UDS was induced by N-methyl-N'
      nitro-N-nitrosoguanidine and 2-aminoanthracene in both rat alveolar macrophages
      and primary lung cells. The results suggest that primary rat lung cells in
      culture possess DNA-repair ability and that the UDS assay may be useful for
      assessing the pulmonary genotoxic effect of chemicals in this cell system.

PMID- 1986286
TI  - The influence of maternal age on radiation-induced chromosome aberrations in
      mouse oocytes.
AB  - The relative sensitivities of dictyate oocytes from young and old female mice to
      radiation-induced chromosome damage were examined in 2 separate experiments.
      Firstly, females were given either 2 or 4 Gy of X-rays and metaphase I stage
      oocytes collected 16.5 days later. Analysis of these cells showed dose-related
      increases in chromosome aberrations in both age groups. The response was
      significantly greater in oocytes of older females. In the second experiment,
      females were given 4 Gy of X-rays and metaphase I stage oocytes collected 3.5
      days later. Again, a significantly larger frequency of aberrations was present in
      cells from older animals. Overall, these 2 experiments provide unambiguous
      evidence that the radiosensitivity of mouse dictyate oocytes increases with
      advancing maternal age.

PMID- 1986288
TI  - Respiratory arrest in near-fatal asthma.
AB  - BACKGROUND AND METHODS: The majority of asthma-related deaths occur outside the
      hospital, and therefore the exact factors leading to the terminal event are
      difficult to ascertain. To examine the mechanisms by which patients might die
      during acute exacerbations of asthma, we studied 10 such patients who arrived at
      the hospital in respiratory arrest or in whom it developed soon (within 20
      minutes) after admission. RESULTS: The characteristics of the group were similar
      to those associated in the literature with a high risk of death from asthma,
      including a long history of the disease in young to middle-aged patients,
      previous life-threatening attacks or hospitalizations, delay in obtaining medical
      aid, and sudden onset of a rapidly progressive crisis. Extreme hypercapnia (mean
      [+/- SD] partial pressure of arterial carbon dioxide, 97.1 +/- 31.1 mm Hg) and
      acidosis (mean [+/- SD] pH, 7.01 +/- 0.11) were found before mechanical
      ventilation was begun, and four patients had hypokalemia on admission. Despite
      the severe respiratory acidosis, no patient had a serious cardiac arrhythmia
      during the resuscitation maneuvers or during hospitalization. We observed
      systemic hypertension and sinus tachycardia in eight patients, atrial
      fibrillation in one, and sinus bradycardia in another. In both patients with
      arrhythmia the heart reverted to sinus rhythm immediately after manual
      ventilation with 100 percent oxygen was begun. The median duration of mechanical
      ventilation was 12 hours, and all patients had normocapnia on discharge from the
      hospital. CONCLUSIONS: We conclude that at least in this group of patients, the
      near-fatal nature of the exacerbations was the result of severe asphyxia rather
      than cardiac arrhythmias. These results suggest that undertreatment rather than
      overtreatment may contribute to an increase in mortality from asthma.

PMID- 1986287
TI  - Cyclosporine for plaque-type psoriasis. Results of a multidose, double-blind
      trial.
AB  - BACKGROUND: Severe plaque-type psoriasis has been successfully treated with
      orally administered cyclosporine, but there has been no comparative, controlled
      evaluation of various dosages and their efficacy and side effects. METHODS: In a
      16-week, double-blind trial, we randomly assigned 85 patients with severe
      psoriasis to receive 3, 5, or 7.5 mg of cyclosporine per kilogram of body weight
      per day or a placebo consisting of the vehicle for the drug. After eight weeks
      the dose could be adjusted to improve safety or efficacy while maintaining
      blinding. RESULTS: The psoriasis improved in a dose-dependent fashion. After
      eight weeks of fixed-dose therapy, 36, 65, and 80 percent of the patients
      receiving 3, 5, and 7.5 mg of cyclosporine per kilogram per day, respectively,
      were rated as being clear or almost clear of psoriasis; each group had
      significant improvement (P less than 0.0001) as compared with the group receiving
      vehicle, in which none of the patients were rated as clear or almost clear. The
      patients who received 5 mg per kilogram were the least likely to require dosage
      adjustments because of side effects or a lack of efficacy. The glomerular
      filtration rate, measured in a subgroup of 34 patients receiving cyclosporine,
      decreased by a median of 16 percent. Higher doses of cyclosporine had greater
      adverse effects on systolic blood pressure, glomerular filtration rate, and serum
      levels of creatinine, uric acid, bilirubin, and cholesterol. Delayed-type
      hypersensitivity reactions to skin-test antigens were reduced by cyclosporine
      administration. Cyclosporine appears to become concentrated in skin. CONCLUSIONS:
      Cyclosporine therapy leads to a rapid and thorough clearing of psoriasis; an
      initial dose of 5 mg per kilogram per day seems to be appropriate. However, the
      safety of cyclosporine for the long-term treatment of psoriasis remains to be
      determined.

PMID- 1986289
TI  - The molecular biology of human immunodeficiency virus type 1 infection.

PMID- 1986290
TI  - An aromatase-producing sex-cord tumor resulting in prepubertal gynecomastia.

PMID- 1986291
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 5-1991. A 61-year-old woman with an abrupt onset of paralysis of
      the legs and impairment of the bladder and bowel function.

PMID- 1986292
TI  - Systemic treatment of severe psoriasis--the role of cyclosporine.

PMID- 1986294
TI  - Waiting patiently.

PMID- 1986293
TI  - Gynecomastia: a continuing diagnostic dilemma.

PMID- 1986295
TI  - House-dust mite allergen and asthma.

PMID- 1986296
TI  - Distal coronary-artery constriction in angina pectoris.

PMID- 1986297
TI  - Syphilis--a reversible cause of nephrotic syndrome in HIV infection.

PMID- 1986298
TI  - Chorionic villus ultrastructure in type II glycogen storage disease (Pompe's
      disease)

PMID- 1986299
TI  - State courts and decisions about life-sustaining treatment.

PMID- 1986300
TI  - Tacrine as a treatment for Alzheimer's dementia: editor's note. An interim report
      from the FDA. A response from Summers et al.

PMID- 1986301
TI  - Visual perception. Grasping the essentials.

PMID- 1986303
TI  - HIV and gag.

PMID- 1986302
TI  - Mercury risk from teeth.

PMID- 1986304
TI  - Library of common protein motifs.

PMID- 1986305
TI  - Fish scales for human origins.

PMID- 1986306
TI  - A neurological dissociation between perceiving objects and grasping them.
AB  - Studies of the visual capacity of neurological patients have provided evidence
      for a dissociation between the perceptual report of a visual stimulus and the
      ability to direct spatially accurate movements toward that stimulus. Some
      patients with damage to the parietal lobe, for example, are unable to reach
      accurately towards visual targets that they unequivocally report seeing.
      Conversely, some patients with extensive damage to primary visual cortex can make
      accurate pointing movements or saccades toward a stimulus presented in their
      'blind' scotoma. But in investigations of visuomotor control in patients with
      visual disorders, little consideration has been given to complex acts such as
      manual prehension. Grasping a three-dimensional object requires knowledge not
      only of the object's spatial location, but also of its form, orientation and
      size. We have examined a patient with a profound disorder in the perception of
      such object qualities. Our quantitative analyses demonstrate strikingly accurate
      guidance of hand and finger movements directed at the very objects whose
      qualities she fails to perceive. These data suggest that the neural substrates
      for the visual perception of object qualities such as shape, orientation and size
      are distinct from those underlying the use of those qualities in the control of
      manual skills.

PMID- 1986307
TI  - Neutrophil influx into an inflammatory site inhibited by a soluble homing
      receptor-IgG chimaera.
AB  - Neutrophil-mediated inflammation is involved in a number of human clinical
      manifestations, including the adult respiratory distress syndrome, multi-organ
      failure and reperfusion injury. One way of inhibiting this type of inflammatory
      response would be to block competitively the adhesive interactions between
      neutrophils and the endothelium adjacent to the inflamed region. The lectin
      containing murine adhesion molecule gp90MEL, the homing receptor, is found on all
      leukocytic cells, including neutrophils. MEL 14, a monoclonal antibody directed
      against this adhesion molecule, blocks lymphocyte traffic to lymph nodes and
      extravasation of neutrophils from blood to inflammatory sites. Here we show that
      administration to mice of a soluble immunoglobulin chimaera containing the murine
      homing receptor extracellular domain significantly decreases the number of
      neutrophils that migrate to the peritoneum in response to the inflammatory
      irritant thioglycollate. These results indicate that soluble forms of a single
      type of adhesion molecule, the homing receptor, could be clinically effective
      compounds for the inhibition of neutrophil-mediated inflammation.

PMID- 1986308
TI  - Macrophage and T cell-line tropisms of HIV-1 are determined by specific regions
      of the envelope gp120 gene.
AB  - Strains of human immunodeficiency virus type 1 (HIV-1) display a high degree of
      biological heterogeneity which may be linked to certain clinical manifestation of
      AIDS. They vary in their ability to infect different cell types, to replicate
      rapidly and to high titre in culture, to down-modulate the CD4 receptor, and to
      cause cytopathic changes in infected cells. Some of these in vitro properties
      correlate with pathogenicity of the virus in vivo. To map the viral determinants
      of the cellular host range of HIV-1, recombinant viruses were generated between
      biologically active molecular clones of HIV-1 isolates showing differences in
      infection of primary peripheral blood macrophages and established T-cell lines.
      We report here that a specific region of the envelope gp120 gene representing 159
      amino-acid residues of glycoprotein gp120 seems to determine macrophage tropism,
      whereas an overlapping region representing 321 amino-acid residues determines T
      cell-line tropism. These studies provide a basis for relating functional domains
      of the HIV-1 env gene to pathogenic potential.

PMID- 1986309
TI  - Phosphorylation of non-muscle caldesmon by p34cdc2 kinase during mitosis.
AB  - One of the profound changes in cellular morphology which occurs during mitosis is
      a massive alteration in the organization of the microfilament cytoskeleton. This
      change, together with other mitotic events including nuclear membrane breakdown,
      chromosome condensation and formation of mitotic spindles, is induced by a
      molecular complex called maturation promoting factor. This consists of at least
      two subunits, a polypeptide of relative molecular mass 45,000-62,000 (Mr 45-62K)
      known as cyclin, and a 34K catalytic subunit which has serine/threonine kinase
      activity and is known as cdc2 kinase. Non-muscle caldesmon, an 83K actin- and
      calmodulin-binding protein, is dissociated from microfilaments during mitosis,
      apparently as a consequence of mitosis-specific phosphorylation. We now report
      that cdc2 kinase phosphorylates caldesmon in vitro principally at the same sites
      as those phosphorylated in vivo during mitosis, and that phosphorylation reduces
      the binding affinity of caldesmon for both actin and calmodulin. Because
      caldesmon inhibits actomyosin ATPase, our results suggest that cdc2 kinase
      directly causes microfilament reorganization during mitosis.

PMID- 1986311
TI  - US challenge to AZT patent.

PMID- 1986310
TI  - Three-dimensional structure of the E. coli DNA-binding protein FIS.
AB  - The factor for inversion stimulation, FIS, is involved in several cellular
      processes, including site-specific recombination and transcriptional activation.
      In the reactions catalysed by the DNA invertases Gin, Hin and Cin, FIS stimulates
      recombination by binding to an enhancer sequence. Within the enhancer, two FIS
      dimers (each 2 x 98 amino acids) bind to two 15-base-pair consensus sequences and
      induce bending of the DNA. Current models propose that the enhancer-FIS complex
      organizes a specific synapse, either through direct interactions with Gin, or by
      modelling the substrate into a configuration suitable for recombination. Using X
      ray analysis at 2.0 A resolution, we now show that FIS is composed of four alpha
      helices tightly intertwined to form a globular dimer with two protruding helix
      turn-helix motifs. The 24 N-terminal amino acids are so poorly defined in the
      electron density map as to make interpretation doubtful, indicating that they
      might act as 'feelers' suitable for DNA or protein (invertase) recognition. We
      infer from model building that DNA has to bend for tight binding to FIS.

PMID- 1986313
TI  - Scientific misconduct. Precedent set as NIH loses court battle.

PMID- 1986312
TI  - Conflict of interest. Then there were four...

PMID- 1986314
TI  - Towards a paradigm shift in biology.

PMID- 1986315
TI  - Appropriate delegation of activities.

PMID- 1986316
TI  - Reducing hospital waste.

PMID- 1986317
TI  - A lesson from school teachers for nurses.

PMID- 1986318
TI  - A simple solution to a complex problem.

PMID- 1986319
TI  - Peers influence one another ...

PMID- 1986320
TI  - Law for the nurse manager. Informed consent process--whose legal duty?

PMID- 1986322
TI  - Technology: nursing the system. The Joint Commission did what you wouldn't.

PMID- 1986321
TI  - Financial management. Congress slices Medicare physician fees.

PMID- 1986323
TI  - Delivery systems and practice models: a dynamic balance.

PMID- 1986324
TI  - Walk a day in my shoes.

PMID- 1986325
TI  - Legislative effects: what's next? Direct reimbursement for nurses.

PMID- 1986326
TI  - Articulating values and assumptions for strategic planning.

PMID- 1986327
TI  - Commercially managed healthcare: an experience.

PMID- 1986328
TI  - Rehabilitation nursing program management.

PMID- 1986329
TI  - A pilot unit approach to shared governance.

PMID- 1986330
TI  - An incentive program ... more than just R & R.

PMID- 1986331
TI  - A decentralized approach to infection control.

PMID- 1986332
TI  - Time for quality assurance.

PMID- 1986334
TI  - Profile of a good manager.

PMID- 1986333
TI  - Nursing process--evaluation of documentation.

PMID- 1986336
TI  - An innovative approach to maintaining critical skills.

PMID- 1986335
TI  - A task force approach to managing aging issues.

PMID- 1986338
TI  - Strategic planning: asking the right questions.

PMID- 1986337
TI  - A model for a self-directed unit.

PMID- 1986339
TI  - The mentor in you.

PMID- 1986340
TI  - Caring for persons with AIDS.

PMID- 1986342
TI  - Professional liability and obstetrical health care delivery.
AB  - Nurse-midwives are finding liability insurance either prohibitively expensive or
      simply unavailable--despite the fact that, in contrast to obstetricians, they are
      rarely sued. As a consequence, maternal health services for rural and poor women
      are rapidly disappearing.

PMID- 1986341
TI  - Why we need a teaching home care program.
AB  - Reports of abuse and financial exploitation have focused attention on home care
      for the elderly and infirm. A Teaching Home Care Program, featuring collaboration
      between schools of nursing and home care agencies, could improve the quality of
      home care and increase the amount of data available on this growing segment of
      the health care system.

PMID- 1986344
TI  - Doctoral preparation and research productivity.
AB  - According to this study, nurses who earn doctorates in any field are likely to go
      on to conduct nursing research. What seems more important than type of degree is
      whether or not the nurses were exposed to computers or participated in faculty
      research while doctoral students.

PMID- 1986343
TI  - Nurse intrapreneurs: the heroes of health care's future.
AB  - Innovation may be the key to cost-effective health care in the 1990s. Those
      institutions that can encourage nurses to become "intrapreneurs," or innovators,
      within the organization will hold an advantage as such encouragement fosters
      staff satisfaction and enhances productivity.

PMID- 1986345
TI  - The invisible nursing practice.
AB  - Although difficult to define and once even dismissed as superfluous, school
      nursing serves as most children's natural entry point into the health care
      system. Indeed, far from being irrelevant, school nurses are the vanguard in the
      fight against drug use, teen pregnancy and child abuse.

PMID- 1986346
TI  - Career mobility for all RNs.
AB  - The move to standardize nursing education at the baccalaureate level has made AD
      and diploma educated nurses uneasy about their professional futures. The
      articulated BS/MS program at the University of California, San Francisco School
      of Nursing is designed to alleviate these fears by giving nonbaccalaureate RNs an
      opportunity to earn BSN and advanced degrees while they continue to work.

PMID- 1986347
TI  - Tools of the trade.

PMID- 1986348
TI  - "Current ranking" should not have been published.

PMID- 1986349
TI  - Dismay at "A current ranking of nursing schools".

PMID- 1986350
TI  - Speaking out in defense of illness care.

PMID- 1986351
TI  - Informed consent doctrine: little danger of liability for nurses.

PMID- 1986352
TI  - The conundrum of recycled leadership.

PMID- 1986353
TI  - Health, nutrition, and public policy.

PMID- 1986354
TI  - Strands hybridize in postreplicative adenovirus overlap recombination.
AB  - We describe a postreplicative mechanism for adenovirus overlap recombination. An
      adenovirus minichromosome system was used to study overlap recombination driven
      by adenovirus DNA replication. Crossing-over appeared to occur equally at, but
      not within, the borders of the overlap between partner molecules. We propose that
      recombination in the minichromosome system proceeds through an intermediate
      formed by direct hybridization of complementary sequences on displaced strands
      generated by adenovirus-specific DNA replication. Some, but not all, heterologous
      regions in the intermediate are susceptible to mismatch correction. This pathway
      is intrinsically nonreciprocal and differs significantly from other adenovirus
      recombinational mechanisms that have been described previously.

PMID- 1986355
TI  - Two types of abnormal genes for plasminogen in families with a predisposition for
      thrombosis.
AB  - The gene coding for plasminogen has been compared with several abnormal genes
      from Japanese patients by the polymerase chain reaction and DNA sequence
      analysis. Two types of abnormal genes coding for plasminogen were identified in
      these patients. In the type I mutation, a guanosine in GCT coding for Ala-601
      near the active-site histidine was replaced by an adenosine resulting in ACT
      coding for threonine. This mutation was also shown by the loss of a cleavage site
      for Fnu4HI endonuclease, a restriction enzyme that recognizes GCTGC but not
      ACTGC. In the type II mutation, a guanosine in GTC coding for Val-355 was
      replaced by a thymidine resulting in TTC coding for phenylalanine. This change
      was readily shown by digestion with Ava II endonuclease, a restriction enzyme
      that recognizes GGTCC and not GTTCC. The type I mutation has been found to be
      identical to a plasminogen variant identified in Japanese patients by amino acid
      sequence analysis and also detected by isoelectric focusing, whereas the type II
      mutation is a unique amino acid substitution in the connecting region between the
      third and fourth kringles in plasminogen. DNA sequence analysis also revealed
      that the abnormal genes carry several silent nucleotide substitutions located
      primarily within introns and 5' and 3' flanking regions.

PMID- 1986356
TI  - Soluble human CD4 elicits an antibody response in rhesus monkeys that inhibits
      simian immunodeficiency virus replication.
AB  - Rhesus monkeys infected with the simian immunodeficiency virus of macaques
      (SIVmac) demonstrate significant virologic and clinical improvement as a result
      of treatment with human recombinant soluble CD4 (rsCD4). We show that human rsCD4
      does not efficiently inhibit SIVmac replication in bone marrow macrophages of
      rhesus monkeys and does not significantly augment bone marrow hematopoietic
      colony formation in vitro. However, plasma of human rsCD4-treated rhesus monkeys
      does exhibit significant anti-SIVmac activity in vitro. Plasma of these animals
      efficiently blocks SIVmac replication in peripheral blood lymphocytes and bone
      marrow macrophages. It also increases granulocyte/macrophage colony formation in
      vitro by bone marrow cells of SIVmac-infected monkeys. This plasma and the IgG
      fraction of plasma from a rhesus monkey immunized with human rsCD4 in adjuvant
      demonstrate reactivity with a soluble form of the rhesus monkey CD4 molecule,
      exhibit binding to CD4+ but not CD8+ concanavalin A-activated rhesus monkey
      peripheral blood lymphocytes, and precipitate the CD4 molecule from surface
      labeled activated rhesus monkey peripheral blood lymphocytes. Moreover, anti
      viral activity is demonstrable in the IgG fraction of plasma from a human rsCD4
      immunized monkey. These studies raise the possibility that a modified human CD4
      molecule serving as an immunogen might elicit an antibody response that could
      potentially induce a beneficial therapeutic response in human immunodeficiency
      virus-infected individuals.

PMID- 1986357
TI  - Structural basis for differential binding of staphylococcal enterotoxin A and
      toxic shock syndrome toxin 1 to class II major histocompatibility molecules.
AB  - The related staphylococcal toxins staphylococcal enterotoxin A (SEA) and toxic
      shock syndrome toxin 1 (TSST-1) are microbial superantigens. They require
      interaction with class II major histocompatibility complex (MHC) molecules to
      activate T cells. We have previously identified a binding site on SEA, the N
      terminal 45 amino acids, as well as its corresponding receptor on the MHC
      antigen, residues 65-85 of the beta chain. To further characterize the structural
      basis for SEA binding to class II MHC molecules we have examined its relationship
      to TSST-1 binding. Both toxins bound similarly to murine A20 cells, but blockage
      of binding was observed only with the homologous toxin, which suggests that the
      binding sites for the two toxins on A20 cells are distinct. In contrast, specific
      binding of SEA was greater than that of TSST-1 on human Raji cells. Further, SEA
      was a better inhibitor of TSST-1 binding than was TSST-1 itself at low
      concentrations, but TSST-1 only minimally inhibited SEA binding. The data suggest
      that TSST-1 interacts with Raji cells at an SEA binding site, but with a lower
      affinity. The peptides SEA-(1-45) and I-A beta b-(65-85) were capable of blocking
      SEA binding on both A20 and Raji cells, but blockage was more effective on A20
      cells. Neither peptide was capable of blocking TSST-1 binding on either cell
      line. The data are compatible with a model in which SEA has a binding site on A20
      cells involving SEA-(1-45) and I-A beta b-(65-85) which is distinct from that
      which binds TSST-1, while at least two binding sites are present on Raji cells.
      One site involves predominantly the residue 1-45 region on SEA and the 65-85
      region of the MHC beta chain, while the other site involves both a different
      region on the SEA molecule and a different site on the class II MHC molecule to
      which it binds. This latter site also binds TSST-1.

PMID- 1986358
TI  - Modeling perceptual grouping and figure-ground segregation by means of active
      reentrant connections.
AB  - The segmentation of visual scenes is a fundamental process of early vision, but
      the underlying neural mechanisms are still largely unknown. Theoretical
      considerations as well as neurophysiological findings point to the importance in
      such processes of temporal correlations in neuronal activity. In a previous
      model, we showed that reentrant signaling among rhythmically active neuronal
      groups can correlate responses along spatially extended contours. We now have
      modified and extended this model to address the problems of perceptual grouping
      and figure-ground segregation in vision. A novel feature is that the efficacy of
      the connections is allowed to change on a fast time scale. This results in active
      reentrant connections that amplify the correlations among neuronal groups. The
      responses of the model are able to link the elements corresponding to a coherent
      figure and to segregate them from the background or from another figure in a way
      that is consistent with the so-called Gestalt laws.

PMID- 1986359
TI  - Modulation of the general anesthetic sensitivity of a protein: a transition
      between two forms of firefly luciferase.
AB  - The activities of most proteins are relatively insensitive to general
      anesthetics. A notable exception is firefly luciferase, whose sensitivity to a
      wide range of anesthetic agents closely parallels that of whole animals. We have
      now found that this sensitivity can be controlled by ATP. The enzyme is
      insensitive at low (microM) concentrations of ATP and very sensitive at high (mM)
      concentrations. The differential sensitivity varies from anesthetic to
      anesthetic, being greatest (about a 100-fold difference) for molecules with large
      apolar segments. This suggests that anesthetic sensitivity is modulated by
      changes in the hydrophobicity of the anesthetic-binding pocket. Parallel changes
      in the binding of the substrate firefly luciferin, for which anesthetics compete,
      indicate that anesthetics bind at the same site as the luciferin substrate. These
      changes in the nature of the binding pocket modify not only the sensitivity to
      anesthetics but also the position of the "cutoff" in the homologous series of
      primary alcohol anesthetics; the cutoff position can vary from octanol to
      pentadecanol, depending upon the concentration of ATP. Our results suggest that
      particularly sensitive anesthetic target sites in the central nervous system may
      possess anesthetic-binding pockets whose polarities are regulated by
      neuromodulatory agents.

PMID- 1986360
TI  - Molecular cloning and characterization of interferon alpha/beta response element
      binding factors of the murine (2'-5')oligoadenylate synthetase ME-12 gene.
AB  - Seven clones encoding interferon response element binding factors have been
      isolated from a mouse fibroblast lambda gt11 cDNA library by using a 32P end
      labeled tandem trimer of the mouse (2'-5')oligoadenylate synthetase gene
      interferon response element as a probe. Clone 16 shares strong similarity (95%)
      at both DNA and amino acid level with YB-1, a human major histocompatibility
      complex class II Y-box DNA-binding protein, and with dbpB, a human epidermal
      growth factor receptor gene enhancer region binding protein. The product of the
      gene represented by clone 16 may represent a factor that regulates multiple genes
      by binding to a variety of 5' regulatory elements. Clone 25 is a 2407-base-pair
      long cDNA and contains a putative 311-amino acid open reading frame corresponding
      to an estimated mass of 35.5 kDa. This putative protein, designated as interferon
      response element binding factor 1 (IREBF-1), contains an acidic domain, three
      heptad repeat leucine arrays, and a region that shares similarity with the yeast
      transcriptional factor GAL4 DNA-binding domain. Furthermore, the C terminus of
      IREBF-1 shows an unusual amphipathic property: within a 79-amino acid range, one
      side of the alpha-helical region contains a preponderance of hydrophobic amino
      acids and the other side contains hydrophilic amino acids. This type of structure
      provides a strong hydrophobic force for protein-protein interaction.

PMID- 1986361
TI  - Evidence for the evolutionary origin of human chromosome 21 from comparative gene
      mapping in the cow and mouse.
AB  - To determine the extent of conservation between bovine syntenic group U10, human
      chromosome 21 (HSA 21), and mouse chromosome 16 (MMU 16), 11 genes were
      physically mapped by segregation analysis in a bovine-hamster hybrid somatic cell
      panel. The genes chosen for study span MMU 16 and represent virtually the entire
      q arm of HSA 21. Because the somatostatin gene (SST), an HSA 3/MMU 16 locus, was
      previously shown to be in U10, the transferrin gene (TF), an HSA 3/MMU 9 marker,
      was also mapped to determine whether U10 contains any HSA 3 genes not represented
      on MMU 16. With the exception of the protamine gene PRM1 (HSA 16/MMU 16), all of
      the genes studied were syntenic on bovine U10. Thus, all homologous loci from HSA
      21 that have been studied in the cow are on a single chromosome. The bovine
      homolog of HSA 21 also carries several HSA 3 genes, two of which have homologous
      loci on MMU 16. The syntenic association of genes from the q arm of HSA 3 with
      HSA 21 genes in two mammalian species, the mouse and the cow, indicates that HSA
      21 may have that contained genes now residing on HSA 3. Additionally, the
      syntenic association of TF with SST in the cow permits the prediction that the
      rhodopsin gene (RHO) is proximal to TF on HSA 3q.

PMID- 1986362
TI  - A -1 ribosomal frameshift in a double-stranded RNA virus of yeast forms a gag-pol
      fusion protein.
AB  - The L-A double-stranded RNA (dsRNA) virus of Saccharomyces cerevisiae has two
      open reading frames (ORFs). ORF1 encodes the 80-kDa major coat protein (gag).
      ORF2, which is expressed only as a 180-kDa fusion protein with ORF1, encodes a
      single-stranded RNA-binding domain and has the consensus sequence for RNA
      dependent RNA polymerases of (+)-strand and double-stranded RNA viruses (pol). We
      show that the 180-kDa protein is formed by -1 ribosomal frame-shifting by a
      mechanism indistinguishable from that of retro-viruses. Analysis of the "slippery
      site" suggests that a low probability of unpairing of the aminoacyl-tRNA from the
      0-frame codon at the ribosomal A site reduces the efficiency of frameshifting
      more than the reluctance of a given tRNA to have its wobble base mispaired.
      Frameshifting of L-A requires a pseudoknot structure just downstream of the shift
      site. The efficiency of the L-A frameshift site is 1.8%, similar to the observed
      molar ratio in viral particles of the 180-kDa fusion protein to the major coat
      protein.

PMID- 1986363
TI  - Functional division and reconstruction of a plasmid replication origin: molecular
      dissection of the oriV of the broad-host-range plasmid RSF1010.
AB  - Two single-stranded DNA initiation signals (designated ssi) present in the origin
      of vegetative DNA replication (oriV) of the broad-host-range plasmid RSF1010 are
      essential for the priming of replication of each complementary DNA strand of this
      plasmid in Escherichia coli. Each of the RSF1010 ssi signals, ssiA and ssiB,
      could be replaced by a primosome assembly site from plasmid pACY184 or from
      bacteriophage phi X174. In these chimeric origins, replication of the strand
      complementary to that containing the primosome assembly site was no longer
      dependent on the RSF1010 primase, protein RepB', but required the E. coli
      primase, DnaG. If both ssiA and ssiB sites of RSF1010 were replaced by primosome
      assembly sites, protein RepB' was no longer essential for the replication at this
      origin, whereas proteins RepA and RepC of RSF1010 were still required. These
      results strongly suggest that the two ssi sites and the RepB' protein actually
      direct the priming of DNA synthesis in the replication of RSF1010, and the
      proteins RepA and RepC are involved in the prepriming events--i.e., the opening
      of the DNA duplex at oriV. It is evident that the origin of RSF1010 can be
      separated into three functional domains and reconstructed by replacing the ssi
      sites with heterologous elements.

PMID- 1986364
TI  - Reconstitution of a group I intron self-splicing reaction with an activator RNA.
AB  - The self-splicing rRNA intron of Tetrahymena thermophila belongs to a subgroup of
      group I introns that contain a conserved extra stem-loop structure termed P5abc.
      A Tetrahymena mutant precursor RNA lacking this P5abc is splicing-defective under
      standard conditions (5 mM MgCl2/200 mM NH4Cl, pH 7.5) in vitro. However, the
      mutant precursor RNA by itself is capable of performing the self-splicing
      reaction without P5abc under different conditions (15 mM MgCl2/2 mM spermidine,
      pH 7.5). We have investigated the functional role of the P5abc in the mechanism
      of the self-splicing reaction. When an RNA consisting of the P5abc but lacking
      the rest of the Tetrahymena intron is incubated with the mutant precursor, the
      self-splicing reaction proceeds highly efficiently under standard conditions (5
      mM MgCl2/200 mM NH4Cl, pH 7.5). Two steps of the bimolecular self-splicing
      reaction can be performed accurately by a shortened precursor RNA containing all
      essential components required in the self-splicing reaction and an activator RNA
      consisting of the P5abc. Gel-mobility-shift assays suggest that two molecules
      associate by a direct RNA-RNA interaction during the splicing reaction. The
      results imply that there might exist other small RNAs whose role is to activate
      ribozymes.

PMID- 1986365
TI  - Genetic disease detection and DNA amplification using cloned thermostable ligase.
AB  - Polymerase chain reaction, using thermostable DNA polymerase, has revolutionized
      DNA diagnostics. Another thermostable enzyme, DNA ligase, is harnessed in the
      assay reported here that both amplifies DNA and discriminates a single-base
      substitution. This cloned enzyme specifically links two adjacent oligonucleotides
      when hybridized at 65 degrees C to a complementary target only when the
      nucleotides are perfectly base-paired at the junction. Oligonucleotide products
      are exponentially amplified by thermal cycling of the ligation reaction in the
      presence of a second set of adjacent oligonucleotides, complementary to the first
      set and the target. A single-base mismatch prevents ligation/amplification and is
      thus distinguished. This method was exploited to detect 200 target molecules as
      well as to discriminate between normal beta A- and sickle beta S- globin
      genotypes from 10-microliters blood samples.

PMID- 1986366
TI  - Nonhomologous chromatid exchange in hereditary and sporadic renal cell
      carcinomas.
AB  - For the development of renal cell carcinomas, it has been suggested that a germ
      line or somatic mutation occurs on one of the homologous chromosomes 3p, and
      subsequently the other 3p segment is lost. We have examined the karyotype and/or
      the allelic combination on chromosomes 3 and 5 by restriction fragment length
      polymorphism analysis in normal kidney and tumor samples from 28 renal cell
      carcinomas that developed in two patients with von Hippel-Lindau disease; we then
      compared the results to those of sporadic tumors. An unbalanced translocation
      between chromosome 3p and 5q or other chromosomes was found to be the most common
      aberration. We developed a model of nonhomologous chromatid exchange involving
      breakpoint clusters at chromosomes 3p13, 3p11.2, 5q22, and 8q11.2. Subsequent
      chromatid segregation may result in net loss of the 3p segment either (i) in one
      step or (ii) after a nondisjunctional loss of the derivative chromosome carrying
      the 3p segment. This general mechanism could also be implicated to explain
      genetic changes occurring in other types of solid tumors.

PMID- 1986367
TI  - crnA encodes a nitrate transporter in Aspergillus nidulans.
AB  - The nucleotide sequence of the Aspergillus nidulans crnA gene for the transport
      of the anion nitrate has been determined. The crnA gene specifies a predicted
      polypeptide of 483 amino acids (molecular weight 51,769). A hydropathy plot
      suggests that this polypeptide has 10 membrane-spanning helices with an extensive
      hydrophilic region between helices six and seven. No striking homology was
      observed between the crnA protein and other reported membrane proteins of either
      prokaryotic or eukaryotic organisms, indicating that the crnA transporter may
      represent another class of membrane protein. Northern blotting results with wild
      type cells show that (i) control of crnA expression is subject to nitrate (and
      nitrite) induction as well as nitrogen metabolite repression and (ii) regulation
      of the crnA gene is exerted at the level of mRNA accumulation, most likely at
      transcription, in response to the nitrogen source in the growth medium.
      Furthermore, similar studies with mutants of nirA and areA control genes and the
      niaD nitrate reductase structural gene show that crnA expression is mediated by
      the products of nirA (nitrate induction control gene), areA (nitrogen metabolite
      repression control gene), and niaD (involved in autoregulation of nitrate
      reductase).

PMID- 1986369
TI  - Epidermal growth factor replaces estrogen in the stimulation of female genital
      tract growth and differentiation.
AB  - The in vivo studies presented here demonstrate that epidermal growth factor (EGF)
      is an important autocrine and/or paracrine mediator of estrogen-induced growth
      and differentiation in mouse uterus and vagina. An antibody specific for EGF
      significantly inhibited estrogen-induced uterine and vaginal growth, thereby
      implicating EGF involvement in estrogen action. Furthermore, EGF administered via
      slow-release pellets in ovariectomized mice acted as a potent uterine and vaginal
      mitogen as well as an inducer of vaginal keratinization. Experiments with
      ovariectomized, adrenalectomized, hypophysectomized mice indicated that EGF
      mitogenesis does not require pituitary or adrenal hormones. Treatment with EGF
      also mimicked estrogen in the induction of uterine lactoferrin (a major estrogen
      inducible secretory protein) mRNA and protein. These data suggest that EGF has
      estrogen-like effects in the promotion of cell growth in the reproductive tract
      and that EGF may serve as an important mediator of estrogen action in vivo.

PMID- 1986368
TI  - Enzymatic aminoacylation of single-stranded RNA with an RNA cofactor.
AB  - A chemically synthesized single-stranded ribonucleotide tridecamer derived from
      the 3' end of Escherichia coli alanine tRNA can be charged with alanine in the
      presence of short complementary RNA oligonucleotides that form duplexes with the
      3' fragment. Complementary 5' oligomers of 9, 8, 6, and 4 nucleotides all confer
      charging of the 3' fragment. Furthermore, in the presence of limiting 5'
      oligomer, greater than stoichiometric amounts of the single-stranded 3' acceptor
      fragment can be aminoacylated. This is due to a reiterative process of transient
      duplex formation followed by charging, dissociation of the 5' oligomer, and then
      rebinding to an uncharged single-stranded ribotridecamer so as to create another
      transient duplex substrate. Thus, a short RNA oligomer serves as a cofactor for a
      charging enzyme, and it thereby makes possible the aminoacylation of single
      stranded RNA. These results expand possibilities for flexible routes to the
      development of early charging and coding systems.

PMID- 1986371
TI  - A model for the quaternary structure of human placental insulin receptor deduced
      from electron microscopy.
AB  - Electrophoretically pure and functionally intact human placental insulin receptor
      was studied by electron microscopy with negative-staining techniques. The
      quaternary structure of the detergent-solubilized receptor was determined. The
      receptor had the shape of a letter T approximately 24 nm in height and 18 nm in
      width with a thickness of the stem and the crossbar of 3-4 nm. No consistent
      change in ultrastructure of the receptor could be detected after the addition of
      insulin alone or insulin and Mn2+/Mg2+/ATP. After partial reduction of the alpha
      2 beta 2 heterotetrameric receptor into alpha beta heterodimers, the electron
      micrographs showed a clear reduction in average size of the molecule with
      disappearance of the T profiles characteristic of the alpha 2 beta 2
      heterotetramers. By incubation of the heterodimers in a phosphorylation medium
      containing insulin, a reassociation to molecules with molecular weights of the
      alpha 2 beta 2 heterotetramer took place judged from SDS/PAGE. Electron
      microscopy showed that the molecule formed larger aggregates, and only a few
      solitary T-shaped copies were seen.

PMID- 1986370
TI  - Localization of a myosin heavy chain-like polypeptide to Drosophila nuclear pore
      complexes.
AB  - Antibodies previously used for immunofluorescence localization of a myosin heavy
      chain-like polypeptide to the nuclear envelope in higher eukaryotic cells
      crossreact with both muscle and nonmuscle isoforms of Drosophila myosin heavy
      chain. Analyses of Drosophila tissue culture cells and premyogenic embryos
      suggest that it is the nonmuscle isoform that is associated with the nuclear
      envelope. Further immunofluorescence and immunoelectron microscopy indicate that
      this polypeptide is associated with nuclear pore complexes. These data support
      the hypothesis put forward previously that myosin or myosin-like molecules play a
      role in pore complex architecture.

PMID- 1986372
TI  - Prothymosin alpha antisense oligomers inhibit myeloma cell division.
AB  - The function of prothymosin alpha has been investigated by using four different
      antisense oligodeoxyribonucleotides directed at selected regions of its mRNA. In
      every case, when synchronized human myeloma cells were released from stationary
      phase by incubation in fresh medium containing antisense oligomers, cell division
      was prevented or inhibited; sense oligomers and random antisense oligomers had no
      effect. A detailed analysis of synchronized cell populations indicated that sense
      treated and untreated cells divided approximately 17 hr after growth initiation,
      whereas cells incubated with antisense oligomer 183, a 16-mer targeted 5 bases
      downstream of the initiation codon, entered mitosis approximately one cell
      division late. The failure to divide correlated directly with a deficit in
      prothymosin alpha and with the continued presence of intact intracellular
      antisense oligomers over a period of at least 24 hr. Because antisense oligomers
      had no effect either on the timing of the induction of prothymosin alpha mRNA
      upon growth stimulation or on mRNA levels seen throughout the cell cycle, we
      concluded that antisense DNA caused specific hybrid arrest of translation. Our
      data suggest that prothymosin alpha is required for cell division. However, there
      is no evidence that prothymosin alpha directly regulates mitosis.

PMID- 1986373
TI  - Molecular cloning, sequence, and tissue distribution of the human ubiquitin
      activating enzyme E1.
AB  - The ubiquitin-activating enzyme E1 catalyzes the first step in ubiquitin
      conjugation. We have cloned and sequenced the cDNA for human E1. This clone
      predicts a protein of 110,450 Da. Cys-194 lies within a region of identity to
      active-site Cys-88 of the ubiquitin carrier protein E2, suggesting a potential
      role for this region in enzymatic function of this protein. In addition, Cys-454
      lies within a region of identity to the thiol ester consensus sequence of several
      proteins involved in thioester formation. Tissue distribution reveals a single
      3.5-kilobase E1 message ubiquitous among tissues and cell lines.

PMID- 1986374
TI  - NMR and molecular modeling evidence for a G.A mismatch base pair in a purine-rich
      DNA duplex.
AB  - 1H NMR experiments indicate that the oligomer 5'-d(ATGAGCGAATA) forms an unusual
      10-base-pair duplex with 4 G.A base pairs (underlined) and a 3' unpaired
      adenosine. NMR results indicate that guanosine imino protons of the G.A
      mismatches are not hydrogen bonded but are stacked in the helix. A G----I
      substitution in either G.A base pair causes a dramatic decrease in duplex
      stability and indicates that hydrogen bonding of the guanosine amino group is
      critical. Nuclear Overhauser effect spectroscopy (NOESY) and two-dimensional
      correlated spectroscopy (COSY) results indicate that the overall duplex
      conformation is in the B-family. Cross-strand NOEs in two-dimensional NOESY
      spectra between a mismatched AH2 and an AH1' of the other mismatched base pair
      and between a mismatched GH8 and GNH1 of the other mismatch establish a purine
      purine stacking pattern, adenosine over adenosine and guanosine over guanosine,
      which strongly stabilizes the duplex. A computer graphics molecular model of the
      unusual duplex was constructed with G.A base pairs containing A-NH2 to GN3 and G
      NH2 to AN7 hydrogen bonds and B-form base pairs on both sides of the G.A pairs
      [5'-d(ATGAGC)]. The energy-minimized duplex satisfies all experimental
      constraints from NOESY and COSY results. A hydrogen bond from G-NH2 of the
      mismatch to a phosphate oxygen is predicted.

PMID- 1986375
TI  - Lack of correlation between DNA methylation and transcriptional inactivation: the
      chicken lysozyme gene.
AB  - We have analyzed the methylation state of all nine CpG sites in the transcription
      start region (-420 to +250 base pairs) of the chicken lysozyme gene by genomic
      sequencing. One of these sites, at -81, lies within the promoter, seven are
      clustered within the first exon, and the last is in the first intron. Five cell
      types and tissues have been investigated to study the relationship between
      methylation level and gene expression. For each cell type used, the majority of
      CpG sites showed a similar level of methylation. Of two gene-nonexpressing
      tissues, erythrocytes are hypomethylated, whereas liver is methylated at most of
      its CpG sites. For gene-expressing tissues, oviduct is completely unmethylated,
      whereas HD-11 culture cells are methylated. Thus no correlation is observed
      between degree of CpG methylation and level of expression of the lysozyme gene.
      The observed methylation patterns are discussed in terms of possible features of
      the local chromatin structure.

PMID- 1986377
TI  - Selection of suppressor methionyl-tRNA synthetases: mapping the tRNA anticodon
      binding site.
AB  - Accurate aminoacylation of a tRNA by Escherichia coli methionyl-tRNA synthetase
      (MTS) is specified by the CAU anticodon. A genetic screening procedure was
      designed to isolate MTS mutants able to aminoacylate a methionine amber tRNA (CUA
      anticodon). Selected suppressor MTS enzymes all possess one or several mutations
      in the vicinity of Trp-461, a residue that is the major contributor to the
      stability of complexes formed with tRNAs having the cognate CAU anticodon.
      Analysis of catalytic properties of purified suppressor enzymes shows that they
      have acquired an additional specificity toward the amber anticodon without
      complete disruption of the methionine anticodon site. It is concluded that both
      positive and negative discrimination toward the binding of tRNA anticodon
      sequences is restricted to a limited region of the synthetase, residues 451-467.

PMID- 1986378
TI  - Reassociation with beta 2-microglobulin is necessary for Db class I major
      histocompatibility complex binding of an exogenous influenza peptide.
AB  - A synthetic peptide corresponding to residues 365-380 of the influenza
      nucleoprotein (NP365-380) has been previously shown to associate with class I
      major histocompatibility complex-encoded molecules and to stimulate cytotoxic T
      lymphocytes [Townsend, A. R. M., Rothbard, J., Gotch, F. M., Bahadur, G., Wraith,
      D. & McMichael, A. J. (1986) Cell 44, 959-968]. We find that intact Db class I
      heterodimers on the cell surface are unreceptive to binding this antigen.
      However, NP365-380 readily associates with Db molecules on the plasma membrane in
      the presence of exogenous beta 2-microglobulin. In addition, there is a second
      pathway through which this peptide associates with class I molecules that
      requires energy and de novo protein synthesis. These findings have implications
      for maintaining the immunological identity of cells and for the use of peptides
      as vaccines for priming cytolytic T-cell immunity.

PMID- 1986376
TI  - Expression and functional properties of transforming growth factor alpha and
      epidermal growth factor during mouse mammary gland ductal morphogenesis.
AB  - Primer-directed enzyme amplification was used to examine epidermal growth factor
      (EGF) and transforming growth factor alpha (TGF-alpha) mRNA transcripts in
      mammary glands of young virgin, mature virgin, midpregnant, and midlactating
      mice. Transcripts for both EGF and TGF-alpha mRNA were detected in virgin and
      pregnant mice, whereas transcripts for EGF mRNA but not TGF-alpha mRNA were
      expressed in 10-day lactating mice. TGF-alpha was localized in the epithelial cap
      cell layer of the advancing terminal end bud and in the stromal fibroblasts at
      the base of the terminal end bud; EGF was localized in the inner layers of the
      terminal end bud and in ductal cells of mammary epithelium. Implantation of
      pellets containing EGF or TGF-alpha into the regressed mammary gland of
      ovariectomized mice stimulated the reappearance of end buds; contralateral glands
      implanted with pellets containing albumin or insulin were not affected. These
      results indicate that an EGF-receptor-mediated pathway remained intact in the
      mammary gland epithelium in the absence of ovarian steroids and that local
      availability of either EGF or TGF-alpha is sufficient to stimulate the pattern of
      normal ductal growth. The detection of EGF and TFF-alpha transcripts at different
      stages of mammary gland development and the different patterns of
      immunolocalization suggest that each polypeptide plays a different role in normal
      mammary gland morphogenesis.

PMID- 1986379
TI  - Evolution of a genetic disease in an ethnic isolate: beta-thalassemia in the Jews
      of Kurdistan.
AB  - beta-Thalassemia is a hereditary disease caused by any of 90 different point
      mutations in the beta-globin gene. Specific populations generally carry a small
      number of mutations, the most common of which are those that are widely
      distributed regionally. The present study constitutes an extensive molecular
      characterization of this disease in a small, highly inbred ethnic group with a
      high incidence of beta-thalassemia--the Jews of Kurdistan. An unusual mutational
      diversity was observed. In 42 sibships 13 different mutations were identified, of
      which 3 are newly discovered: a C----A transversion at -88 to the cap site, a
      frameshift in codon 36/37, and an A----G transition in the polyadenylylation
      signal. Four of the mutations are unique to Kurdish Jews and have not been
      discovered in any other population. A fifth was found outside Kurdish Jews only
      in an Iranian from Khuzistan, a region bordering Kurdistan. Two-thirds of the
      mutant chromosomes carry the mutations unique to Kurdish Jews. We traced the
      origin of the mutations to specific geographic regions within Kurdistan. This
      information, supported by haplotype analysis, suggests that thalassemia in
      central Kurdistan (northern Iraq) has evolved primarily from multiple mutational
      events. In Turkish Kurdistan, the primary mechanism is genetic admixture with the
      local population. In Iranian Kurdistan, a founder effect appears to be partly
      responsible. We conclude that several evolutionary mechanisms contributed to the
      evolution of beta-thalassemia in this small ethnic isolate.

PMID- 1986380
TI  - Somatic mosaicism and female-to-female transmission in a kindred with hemophilia
      B (factor IX deficiency).
AB  - Studies have shown that hemophilia B (Christmas disease; factor IX deficiency)
      results from many different mutations in the factor IX gene, of which greater
      than 95% are single nucleotide substitutions. This study has identified a
      previously unreported form of hemophilia B in a patient who was a somatic mosaic
      for a guanine-to-cytosine transversion at nucleotide 31,170 in the factor IX
      gene. This point mutation changes the codon for residue 350 in the catalytic
      domain of factor IX from a cysteine to a serine. We used differential termination
      of primer extension to confirm and measure the degree of mosaicism. Our study
      shows that a varying proportion of cells from hepatic, renal, smooth muscle, and
      hematopoietic populations possessed normal as well as mutant factor IX sequences.
      These results indicate that the mutation in this patient occurred either as an
      uncorrected half-chromatid mutation in the female gamete or as a replication or
      postreplication error in the initial mitotic divisions of the zygote preceding
      implantation. In addition, this kindred also contains two females in successive
      generations who have moderately severe factor IX deficiency. The molecular
      pathogenesis of this latter phenomenon has been studied and seems to relate to
      the unaccompanied expression of the mutant factor IX gene consequent upon a
      second, as yet undefined, genetic event that has prevented inactivation of
      sequences including the mutant factor IX gene on the X chromosome inherited from
      the affected male.

PMID- 1986381
TI  - Extrathymic origin of intestinal intraepithelial lymphocytes bearing T-cell
      antigen receptor gamma delta.
AB  - The kinetics of postnatal intestinal colonization by T cells carrying gamma delta
      and alpha beta T-cell antigen receptors were studied in nude and normal mice by
      flow cytometry and immunohistology. Furthermore, gamma delta and alpha beta T
      cell development was analyzed in lethally irradiated mice that were reconstituted
      by fetal liver precursors with or without a thymus. Our results establish that a
      major subpopulation of gamma delta intestinal intraepithelial lymphocytes is
      produced from uncommitted precursors at extrathymic sites. This work further
      shows that a small pool of T cells carrying alpha beta T-cell receptors can also
      differentiate extrathymically from CD3- fetal liver precursors but with rates of
      production and peripheral expansion much reduced as compared with those observed
      in thymus-bearing animals.

PMID- 1986383
TI  - Dimerization of mammalian progesterone receptors occurs in the absence of DNA and
      is related to the release of the 90-kDa heat shock protein.
AB  - In this study we have demonstrated that dimerization of mammalian progesterone
      receptors (PR) occurs in the absence of DNA. A specific immune coisolation assay
      was performed on extracts of T-47D human breast cancer cells with a monoclonal
      antibody specific for the full-length B form of progesterone receptor (PR-B).
      This resulted in coisolation of significant amounts of truncated form-A receptors
      (PR-A), indicating the presence of stable PR-A.PR-B dimers in solution. A
      positive correlation was observed between the ability of different receptor forms
      to oligomerize in solution and their ability to bind to specific DNA sequences.
      The ability to form stable PR-A.PR-B oligomers in the absence of DNA was also
      found to correlate with release of 90-kDa heat shock protein (hsp90) from the
      unactivated PR complex. These results support the hypothesis that dimerization in
      the absence of DNA is an important mechanism controlling receptor DNA-binding
      function and that hsp90 release may be a key step regulating dimerization. This
      suggests that hsp90 may function to repress DNA-binding activity indirectly by
      blocking receptor dimerization.

PMID- 1986384
TI  - Structural model of the nucleotide-binding conserved component of periplasmic
      permeases.
AB  - The amino acid sequences of 17 bacterial membrane proteins that are components of
      periplasmic permeases and function in the uptake of a variety of small molecules
      and ions are highly homologous to each other and contain sequence motifs
      characteristic of nucleotide-binding proteins. These proteins are known to bind
      ATP and are postulated to be the energy-coupling components of the permeases.
      Several medically important eukaryotic proteins, including the multidrug
      resistance transporters and the protein encoded by the cystic fibrosis gene, are
      also homologous to this family. By multiple sequence alignment of these 17
      proteins, the consensus sequence, secondary structure, and surface exposure were
      predicted. The secondary structural motifs that are conserved among nucleotide
      binding proteins were identified in adenylate kinase, p21ras, and elongation
      factor Tu by superposition of their known tertiary structures. The equivalent
      secondary structural elements in the predicted conserved component were located.
      These, together with sequence information, served as guides for alignment with
      adenylate kinase. A model for the structure of the ATP-binding domain of the
      permease proteins is proposed by analogy to the adenylate kinase structure. The
      characteristics of several permease mutations and biochemical data lend support
      to the model.

PMID- 1986382
TI  - Sequence and functional expression in Xenopus oocytes of a human insulinoma and
      islet potassium channel.
AB  - Regulation of insulin secretion involves the coordinated control of ion channels
      in the beta-cell membrane. We have isolated and characterized cDNA and genomic
      clones encoding a voltage-dependent K+ channel isoform expressed in human islets
      and in a human insulinoma. This K+ channel isoform, designated hPCN1, with a
      deduced amino acid sequence of 613 residues (Mr = 67,097), is related to the
      Shaker family of Drosophila K+ channels. hPCN1 is homologous to two other human
      K+ channel isoforms we have isolated, hPCN2 and hPCN3, with 55% and 65% amino
      acid sequence identity, respectively. The electrophysiological characteristics of
      hPCN1 were determined after microinjection of synthetic RNA into Xenopus oocytes.
      Two-microelectrode voltage-clamp recordings of oocytes injected with hPCN1 RNA
      revealed a voltage-dependent outward K+ current that inactivated slowly with
      time. Outward currents were inhibited by 4-aminopyridine with a Ki less than 0.10
      mM and were relatively insensitive to tetraethylammonium ion or Ba2+. A delayed
      rectifier K+ channel such as hPCN1 could restore the resting membrane potential
      of beta cells after depolarization and thereby contribute to the regulation of
      insulin secretion.

PMID- 1986385
TI  - Initial extracellular forms of Plasmodium falciparum: their ultrastructure and
      their definition with monoclonal antibodies.
AB  - Merozoites of the erythrocytic stage of the human malaria parasite Plasmodium
      falciparum, when placed under appropriate conditions in a culture medium with
      erythrocyte extract, differentiate into early trophic forms. These forms have
      much the same ultrastructure as rings of the same age that have developed
      intracellularly and have then been freed from their host cells by immune lysis.
      However, these forms differ in two respects: the extracellular forms have only
      their single plasma membrane, whereas the forms freed from host cells have, in
      addition, a surrounding parasitophorous vacuole membrane; the forms that develop
      extracellularly have fewer ribosomes. Five monoclonal antibodies against the ring
      stage have been prepared and characterized. Their pattern of immunofluorescence
      localization differs in merozoites as compared with rings, but their pattern is
      identical in rings developed extracellularly and those developed intracellularly.
      These results and the observations on fine structure demonstrate biochemical and
      morphological differentiation in the extracellular forms.

PMID- 1986386
TI  - Pancreatic tumor pathogenesis reflects the causative genetic lesion.
AB  - Transgenic mice in which c-myc expression is targeted to pancreatic acinar cells
      develop mixed acinar/ductal pancreatic adenocarcinomas between 2 and 7 months of
      age. This contrasts with the effect on pancreas of the simian virus 40 tumor
      antigen or activated ras, which in adult mice causes lesions composed exclusively
      of acinar-like cells. Furthermore, during an early stage of myc-induced
      pathology, transformed acinar-derived cells appear within islets, suggesting that
      islet hormones may influence the progression of these exocrine pancreatic tumors.
      These findings demonstrate that the initial oncogenic alteration can influence
      the pattern of subsequent tumor pathogenesis and, given that human exocrine
      pancreatic tumors are predominantly ductal adenocarcinomas, support the
      suggestion that transformed acinar cells may contribute to the genesis of this
      serious disease in man.

PMID- 1986387
TI  - Calcium pump of the plasma membrane.

PMID- 1986388
TI  - Mesocorticolimbic dopaminergic network: functional and regulatory roles.

PMID- 1986389
TI  - Chloride transport by high-resistance heterocellular epithelia.

PMID- 1986390
TI  - Motifs of protein phosphorylation and mechanisms of reversible covalent
      regulation.

PMID- 1986391
TI  - Cardiovascular response to stress.
AB  - The behavioral characteristics of psychological stressors have been operationally
      defined. A psychological stressor is one that causes a stress response in a
      predictable percentage of index subjects. However, it may not always produce a
      stress response, and the probability of producing such a response depends on
      interactions between the behavioral situation and the individual involved. Thus
      there is a danger that a psychological stressor will be defined according to the
      stress response it causes rather than its structural characteristics. The
      characteristics that enhance the likelihood that a psychological stressor will
      cause a stress response are its novel, challenging, or threatening aspects that
      engage a subject in continuous active mental effort. The intensity of the stress
      response depends on the intensity of mental effort exerted to meet a challenging
      situation, whether or not that situation is perceived as threatening. The
      behavioral response to a psychological stressor also has been defined. It
      includes somatomotor, neuroendocrine, and cardiovascular components. The
      somatomotor response to stressful psychological events includes purposeful active
      coping to counter the challenge or threat posed by the stressor. The
      neuroendocrine response includes a combination of pituitary-adrenal cortical and
      hypothalamic-sympathetic-adrenal medullary secretions. The cardiovascular
      response includes a combination of increased rate and force of cardiac
      contraction, skeletal muscle vasodilation, venoconstriction, splanchnic
      vasoconstriction, renal vasoconstriction, and decreased renal excretion of
      sodium. Of all the modifiers that influence the stress response to a
      psychological stressor, family history is the one most likely to have an effect.
      A family history of essential hypertension increases the likelihood that a
      subject will respond to a psychological stressor with a cardiovascular stress
      response pattern. Other predisposing characteristics that increase the likelihood
      of a stress response include behavioral patterns of response to challenge or
      threat but may also include anatomic or biochemical characteristics that increase
      susceptibility to neurogenic activation of central aminergic mechanisms.

PMID- 1986392
TI  - Optical approaches to ontogeny of electrical activity and related functional
      organization during early heart development.
AB  - Direct intracellular measurement of electrical events in the early embryonic
      heart is impossible because the cells are too small and frail to be impaled with
      microelectrodes; it is also not possible to apply conventional
      electrophysiological techniques to the early embryonic heart. For these reasons,
      complete understanding of the ontogeny of electrical activity and related
      physiological functions of the heart during early development has been hampered.
      Optical signals from voltage-sensitive dyes have provided a new powerful tool for
      monitoring changes in transmembrane voltage in a wide variety of living
      preparations. With this technique it is possible to make optical recordings from
      the cells that are inaccessible to microelectrodes. An additional advantage of
      the optical method for recording membrane potential activity is that electrical
      activity can be monitored simultaneously from many sites in a preparation. Thus,
      applying a multiple-site optical recording method with a 100- or 144-element
      photodiode array and voltage-sensitive dyes, we have been able to monitor, for
      the first time, spontaneous electrical activity in prefused cardiac primordia in
      the early chick embryos at the six- and the early seven-somite stages of
      development. We were able to determine that the time of initiation of the
      contraction is the middle period of the nine-somite stage. In the rat embryonic
      heart, the onset of spontaneous electrical activity and contraction occurs at the
      three-somite stage. In this review, a new view of the ontogenetic sequence of
      spontaneous electrical activity and related physiological functions such as ionic
      properties, pacemaker function, conduction, and characteristics of excitation
      contraction coupling in the early embryonic heart are discussed.

PMID- 1986393
TI  - Fever: role of pyrogens and cryogens.
AB  - The biology of cytokines is one of the most rapidly growing areas of biomedical
      research. It is understandable why the assumption was made several years ago that
      EP was equivalent to IL-1 (both alpha and beta) and subsequently to IL-1 alpha,
      IL-1 beta, and TNF. However, as more data have been obtained, it has become
      clearer that many cytokines and hormones are capable of participating in the
      febrile response. It is also becoming apparent that EPs and ECs might influence
      body temperature during nonpathological states, perhaps contributing to the
      elevation in temperature during or after exercise, the circadian variation in
      temperature, and others. Medical textbooks have begun to list IL-1 as the EP. As
      I attempted to make clear in this review, evidence that IL-1 alpha is a
      circulating EP is poor. The evidence is considerably stronger that IL-1 beta is
      an EP, at least during LPS-induced fever in rodents. The point I have tried to
      emphasize is that before any cytokine or hormone can be characterized as an EP or
      EC (or, for that matter, as being involved in any of the acute phase responses),
      clearly established rules must be followed, which are patterned after the
      traditional criteria used by Koch to distinguish a pathogenic microorganism from
      a benign one. As summarized in Tables 4 and 5, there are many candidates for EPs
      and ECs, but much more experimental evidence is essential before we gain a clear
      understanding of the relationship between contact with an exogenous pyrogen, the
      release of EPs and ECs, and the development of fever.

PMID- 1986394
TI  - The W values for photons and electrons in mixtures of argon and alkanes.
AB  - The mean energy required to form an ion pair for 5.89-keV 55Fe and 1.49-keV Al
      photons in mixtures of argon-methane and argon-butane gas was measured using the
      proportional-counter technique. The measured W values in the mixtures are lower
      than what is expected for regular mixtures, i.e., mixtures without an appreciable
      intermolecular energy transfer between the mixture components. The additional
      ionization yield through the nonmetastable Penning processes reaches a maximum
      abruptly at very low partial pressure of polyatomic admixtures (alkanes),
      decreasing steadily with higher admixture partial pressure.

PMID- 1986396
TI  - Long-term overproduction of collagen in radiation-induced fibrosis.
AB  - Collagen metabolism was investigated in the fibrotic tissue which developed in
      pig thigh muscle 6 to 15 months after acute gamma irradiation. During this
      period, total collagen deposits in the fibrotic tissue increased 10-fold compared
      to the healthy muscle tissue. These deposits were composed mainly of type I and
      III collagen, and the type I/type III ratio was lower in the fibrotic than in the
      muscle tissue. Small pieces of both fibrotic and muscle tissue were incubated
      with [14C]proline. The [14C]hydroxyproline content of the fibrotic tissue
      reflected large concomitant increases in the synthesis of total collagen, mainly
      of types I and III, which rose 14- and 17-fold, respectively. Similarly, the
      level of type I and type III procollagen mRNAs rose 9- and 5-fold, respectively,
      in the fibrotic tissue versus the muscle tissue. These results suggest that
      procollagen gene transcription or RNA maturation in the cell nuclei is activated
      in the fibrotic tissue. The possibility that such activation is due to the long
      term inflammatory state of this tissue is discussed.

PMID- 1986395
TI  - A quantitative model of DNA fragments generated by ionizing radiation, and
      possible experimental applications.
AB  - We derive an equation for observed frequencies of DNA fragments as a function of
      size. In this derivation, we consider an experimental system where fragments are
      generated by random, independent double-strand breaks on chromosomes (or other
      large DNA molecules) and then separated by size on agarose gels. When visualizing
      these fragments using Southern hybridization techniques (employing a site
      specific probe), we predict an intensity distribution that has unusual
      properties. In particular, peaks in the fragment size distribution depend not
      only on standard breakage parameters, but also on the location of the
      hybridization site. Our model is consistent with experimental and theoretical
      results reported elsewhere, where measurements of peaks are used for the physical
      mapping of genes. Further, we propose that similar experiments might be suitable
      for precise measurements of the parameters of double-strand breakage (as an
      alternative to neutral filter elutions and neutral sucrose gradients) and for
      testing the assumption of random, independent breakage for different types of
      radiation.

PMID- 1986397
TI  - Response of erythrocytes to heat in the presence of D2O, glycerol, and anisotonic
      saline.
AB  - Mammalian erythrocytes that lack cytoplasmic organelles and a nucleus are a
      useful model for studying the effect of heat on the cell membrane and
      cytoskeleton. The effect of heat on the membrane bilayer and cytoskeleton of
      erythrocytes is remarkably similar to that observed in nucleated cells. Some
      concentrations of D2O and glycerol can effectively protect erythrocytes from heat
      induced damage to the membrane and cytoskeleton. These results are similar to
      observations in nucleated cells. Heating erythrocytes in some concentrations of
      anisotonic NaCl solutions reduced damage, an observation that does not apply to
      enhanced killing of nucleated cells. This difference implies that some components
      of the cytoplasm or nucleus, or both, may contribute to the enhancement of
      cytotoxicity of nucleated cells when they are heated in the anisotonic NaCl
      solution. Incremental heating, dividing a heat treatment into two fractions, and
      preheating of erythrocytes all modify the effect of heat on erythrocytes
      slightly, but the results suggest little, if any, development of thermotolerance.
      The response of chicken erythrocytes is similar to that of mammalian
      erythrocytes, although higher temperatures are required to produce a heat effect
      in chicken erythrocytes. These observations suggest that the characteristic
      differences in heat sensitivity in nucleated and enucleated cells involve
      components other than the cell membrane.

PMID- 1986398
TI  - The effect of irradiation in air or in hyperbaric oxygen on the Fib/T tumor in
      WHT mice pretreated with a hypoxic gas mixture.
AB  - The effect of exposing WHT mice bearing the Fib/T tumor to a low-oxygen
      environment (8, 10, and 15% oxygen) for 48 h or 72 h before irradiation was
      compared, using an in vitro colony-forming excision assay, to the effect obtained
      when mice were pretreated with air. The response of the Fib/T tumor to radiation
      delivered in air was improved both by a 48-h and by a 72-h exposure of the
      animals to 8, 10, and 15% oxygen. However, the greatest tumor sensitization was
      achieved when mice were kept in 8% oxygen for 48 h before irradiation. These
      results are interpreted and discussed in relation to increases in the 2,3-DPG
      concentration, which were shown to occur when mice were exposed to a reduced
      oxygen environment. The relative importance of two models proposed to explain
      these findings is assessed. If mice pretreated with air were irradiated in
      hyperbaric oxygen, a similar tumor response was observed compared to that when
      mice were exposed to 8% oxygen for 48 h and then irradiated in air.

PMID- 1986399
TI  - Early radiation response of the canine heart and lung.
AB  - In this study three groups of four adult beagle dogs were irradiated with a 12-Gy
      single dose to the thorax. The fields used were the entire thorax, the entire
      thorax with a heart block in place, and the heart with one-third of the lung
      volume. The response of the lung was evaluated by cellular and biochemical
      analysis of sequential bronchoalveolar lavage fluids, blood gas analysis,
      physical examination, and histopathology. Sparing a small volume of lung improved
      survival. Cardiac function was evaluated by right heart catheterization,
      echocardiography, physical exam, and histopathology. Pulmonary artery pressure
      was increased in all dogs, mean systemic artery pressure was decreased in all
      dogs, and no difference could be shown among the groups. These effects are likely
      secondary to a reduced pulmonary capillary volume. Stroke volume was
      significantly deceased in dogs that had their hearts included in the field but
      not in dogs with their hearts shielded. This effect was not thought to be
      secondary to lung injury. The influence of lung irradiation on cardiac function
      was limited to pulmonary hypertension. Pulmonary hypertension may be enhanced by
      the release of vasoactive compounds. Pulmonary hypertension may contribute to
      radiation-induced heart failure.

PMID- 1986400
TI  - Lipid composition of the membranes from cells of two rat tumors and its
      relationship to tumor thermosensitivity.
AB  - A plasma membrane-rich fraction has been separated from liver cells and cells of
      two solid rat tumors. D23 hepatoma and MC7 sarcoma. On the basis of marker enzyme
      activity the membranes separating at the 31-41% interface on the discontinuous
      sucrose gradient were enriched 15- to 19-fold. No significant differences in the
      phospholipid (PL) composition of the three membrane fractions were observed. The
      PL fatty acid (FA) composition showed that the percentage of unsaturated FA in
      all three membranes was between 43 and 48%. However, the oleic acid:PUFA ratio
      was much greater from tumor membranes. Membrane cholesterol was also
      significantly lower for cells from both tumors compared with liver cells. The DPH
      fluorescence polarization of the membrane fractions showed that the membranes
      from cells of both tumors are significantly less ordered than those of liver at
      all temperatures measured (4-50 degrees C). The Mg2+ ATPase activity of the
      plasma membranes is inactivated by hyperthermia treatments. The enzyme from liver
      cells was more thermostable (LT50 = 53.86 degrees C) than that from cells of
      either D23 (LT50 = 47.51 degrees C) or MC7 (LT50 = 46.34 degrees C) tumors.

PMID- 1986401
TI  - Mechanism of radiosensitization by halogenated pyrimidines: effect of BrdU on
      cell killing and interphase chromosome breakage in radiation-sensitive cells.
AB  - The effect of BrdU incorporation on cell radiosensitivity as well as on the
      induction of chromosome damage by radiation was studied in plateau-phase xrs-5
      cells using the premature chromosome condensation (PCC) method. It is well known
      that xrs-5 cells are sensitive to ionizing radiation and defective in the repair
      of radiation-induced DNA double-strand breaks, chromosome damage, and potentially
      lethal damage (PLD). Compared to repair-proficient CHO 10B cells, a reduction was
      observed in the overall BrdU-mediated radiosensitization in plateau-phase xrs-5
      cells for the same degree of thymidine replacement. This finding is interpreted
      with a model for BrdU-induced radiosensitization advanced previously, in which
      two distinct components act to produce the overall radiosensitization observed.
      One component involves processes associated with the increase in initial damage
      (DNA and chromosome) production per unit absorbed dose and causes an increase in
      the slope of the survival curve, while the second component involves enhanced
      fixation of radiation-induced damage (PLD) and causes a reduction in the width of
      the shoulder of the survival curve. It is suggested that in plateau-phase xrs-5
      cells, the deficiency in the repair of radiation-induced damage compromises BrdU
      mediated radiosensitization by leaving active only the radiosensitization
      component that is associated with an increase in damage induction. Enhancement of
      cell killing by BrdU in plateau-phase xrs-5 cells resulted in a decrease in D0,
      the relative value of which was similar to the relative increase in the
      production of chromosome damage as measured by the PCC method. The relative
      values for the change in D0 and the production of chromosome aberrations were
      similar in plateau-phase CHO 10B and xrs-5 cells, suggesting that the
      physicochemical and/or biochemical processes associated with this phenomenon are
      the same in the two cell lines. Radiosensitization of a magnitude similar to that
      observed in exponentially growing CHO 10B cells was induced by BrdU in
      exponentially growing xrs-5 cells. This effect is attributed to a partial
      expression of the repair gene (transiently during S phase in all cells, or
      throughout the cycle in a fraction of cells) that permits some repair of
      radiation-induced damage and which is compromised by BrdU.

PMID- 1986402
TI  - Residual activation events functional after irradiation of mouse splenic
      lymphocytes.
AB  - The radioresistance of lymphocytes increases after mitogenic stimulation,
      suggesting that a radiosensitive activation event contributes to the overall
      radiosensitivity of lymphocytes. We have sought to identify this activation event
      by determining the extent of activation of mitogen-stimulated lymphocytes
      previously exposed to growth-inhibiting doses of radiation. Mouse splenic
      lymphocytes were exposed to 0-15 Gy 137Cs radiation, and structural and
      functional damage were assayed. Although damage to cellular thiols and nonprotein
      thiols was modest, there was a significant loss of viability by 6 h as determined
      by uptake of propidium iodide (PI). Since cells did not die immediately after
      irradiation, the activation events which remained were evaluated. Growth
      inhibiting doses of radiation left cells partially responsive to mitogen, in that
      cells were able to exit G0 phase, but they could progress no further into the
      cell cycle than G1a phase. It is important to note that assessment of viability
      by uptake of PI indicated substantial cell death after 15 Gy (45%, 6 h; 90%, 24
      h); however, cell cycle analysis at 24 h indicated no significant decrease in
      progression from G0 to G1a phase. The LPS-stimulated response of B cells was more
      radiosensitive than the Con A-stimulated response of T cells. Further analysis of
      the Con A response indicated that production of interleukin-2 (IL-2) was
      unaffected, but expression of the IL-2 receptor was inhibited. Inhibition of poly
      ADP-ribosylation and damage to lipids did not prevent the lack of mitogen
      responsiveness, since neither the ADP-ribose transferase inhibitor 3
      aminobenzamide nor lipid radical scavengers had restorative effects on the
      mitogenic response. Nor was Con A-stimulated incorporation of [3H]thymidine
      restored with inhibitors of prostaglandin or leukotriene synthesis, suggesting
      that inhibition was due to direct effects on the Con A responders, and not
      indirect effects mediated by arachidonate metabolites. These results indicate
      that growth-inhibiting doses of radiation trigger the process in lymphocytes that
      culminates in apoptosis, yet leave the cells partially responsive to mitogenic
      stimuli.

PMID- 1986403
TI  - Translocation of hsp-70 and protein synthesis during continuous heating at mild
      temperatures in HeLa cells.
AB  - We have investigated intracellular translocation of hsp-70 and the synthesis of
      hsp-70 and total protein during heating at moderate temperatures in HeLa cells.
      When cells were heated at temperatures above 41 degrees C, hsp-70 translocated
      from the cytoplasm into the nuclei and apparently accumulated in nucleoli within
      10 min. At temperatures above 42 degrees C, hsp-70 remained in the nuclei during
      heating. When cells were heated at 41 degrees C, the hsp-70 which had
      translocated into the nuclei returned gradually to the cytoplasm during heating.
      Synthesis of hsp-70 increased to three- to fourfold that in control cells, then
      decreased to the control level by 6-8 h. Total protein synthesis first decreased
      to 60% of the control level, then gradually recovered by 4 h. This indicates the
      acquisition of translational tolerance during heating at 41 degrees C. The return
      of hsp-70 to the cytoplasm is related to the recovery of total protein synthesis.
      Similar results were obtained at 42 degrees C heating in heat-induced
      thermotolerant cells. From these results, it is suggested that translocation of
      hsp-70 into the nuclei is very important for the recovery of protein synthesis
      (acquisition of translational tolerance) during heating at moderate temperatures.
      Also, cycloheximide and puromycin appeared to lower the temperature threshold
      about 1 degree C with respect to the translocation of hsp-70.

PMID- 1986405
TI  - Threshold-like dose of local beta irradiation repeated throughout the life span
      of mice for induction of skin and bone tumors.
AB  - The backs of female ICR mice were irradiated with beta rays from 90Sr-90Y three
      times a week throughout life. Previously we observed 100% tumor incidence at five
      different dose levels ranging from 1.5 to 11.8 Gy per exposure, but no tumor on
      repeated irradiation with 1.35 Gy for 300 days (Radiat. Res. 115, 488, 1988). In
      the present study, delay of tumor development was again seen at a dose of 1.5 Gy
      per exposure, with further delay at 1.0 Gy. The final tumor incidence was 100%
      with these two doses. At 0.75 Gy per exposure, no tumor appeared within 790 days
      after the start of irradiation, but one osteosarcoma and one squamous cell
      carcinoma did finally appear. These findings indicate a threshold-like response
      of tumor induction in this repeated irradiation system and further suggest that
      the apparent threshold may be somewhat less than 0.75 Gy per exposure.

PMID- 1986404
TI  - Induction of sperm head abnormalities by incorporated radionuclides: dependence
      on subcellular distribution, type of radiation, dose rate, and presence of
      radioprotectors.
AB  - In contrast to the biological effects caused by exposure to external beams of
      radiation, the effects of tissue-incorporated radionuclides are highly dependent
      on the type of radiation emitted and on their distribution at the macroscopic,
      microscopic, and subcellular levels, which are in turn determined by the chemical
      nature of the radionuclides administered. Induction of abnormalities of sperm
      heads in mice is investigated in this work after the injection of a variety of
      radiochemicals including alpha emitters. When the initial slopes of the dose
      response curves are used to compare the relative biological effectiveness (RBE)
      of different radiocompounds, the alpha particles emitted in the decay of 210Po
      are more effective than Auger electrons emitted by 125I incorporated in the DNA
      of the spermatogonial cells, and both emissions are more effective than X rays.
      It is also shown that the Auger emitters (125I, 111In) distributed in the cell
      nucleus are more efficient in producing abnormalities than the same radionuclides
      localized in the cytoplasm. These findings are consistent with our earlier
      observations, where spermatogonial cell survival is assayed as a function of the
      testicular absorbed dose. Further, chronic irradiation of testis with gamma rays
      from intratesticularly administered 7Be is about three times more effective in
      causing abnormalities than a single acute exposure to 120-kVp X rays. The
      resulting RBE values correlate well with our data on sperm head survival with the
      same radiocompounds. Finally, the radioprotector cysteamine, when administered in
      small, nontoxic amounts, significantly reduces the incidence of sperm
      abnormalities from alpha-particle radiation as well as emissions from 125I
      incorporated into DNA, the dose reduction factors being 10 and 14, respectively.

PMID- 1986407
TI  - NSF centers rise above the storm.

PMID- 1986406
TI  - Carcinogens and human health: Part 2.

PMID- 1986408
TI  - Leroy Hood says no.

PMID- 1986409
TI  - Research papers: who's uncited now?

PMID- 1986410
TI  - Making 3-D movies of the heart.

PMID- 1986411
TI  - On the road to mandelate ... racemase.

PMID- 1986414
TI  - Sky dreams: high above the clouds.

PMID- 1986413
TI  - Generation of calcium oscillations in fibroblasts by positive feedback between
      calcium and IP3.
AB  - A wide variety of nonexcitable cells generate repetitive transient increases in
      cytosolic calcium ion concentration ([Ca2+]i) when stimulated with agonists that
      engage the phosphoinositide signalling pathway. Current theories regarding the
      mechanisms of oscillation disagree on whether Ca2+ inhibits or stimulates its own
      release from internal stores and whether inositol 1,4,5-trisphosphate (IP3) and
      diacylglycerol (DG) also undergo oscillations linked to the Ca2+ spikes. In this
      study, Ca2+ was found to stimulate its own release in REF52 fibroblasts primed by
      mitogens plus depolarization. However, unlike Ca2+ release in muscle and nerve
      cells, this amplification was insensitive to caffeine or ryanodine and required
      hormone receptor occupancy and functional IP3 receptors. Oscillations in [Ca2+]i
      were accompanied by oscillations in IP3 concentration but did not require
      functional protein kinase C. Therefore, the dominant feedback mechanism in this
      cell type appears to be Ca2+ stimulation of phospholipase C once this enzyme has
      been activated by hormone receptors.

PMID- 1986412
TI  - Atomic structure of ferredoxin-NADP+ reductase: prototype for a structurally
      novel flavoenzyme family.
AB  - The three-dimensional structure of spinach ferredoxin-NADP+ reductase (NADP+,
      nicotinamide adenine dinucleotide phosphate) has been determined by x-ray
      diffraction at 2.6 angstroms (A) resolution and initially refined to an R factor
      of 0.226 at 2.2 A resolution. The model includes the flavin-adenine dinucleotide
      (FAD) prosthetic group and the protein chain from residue 19 through the carboxyl
      terminus at residue 314 and is composed of two domains. The FAD binding domain
      (residues 19 to 161) has an antiparallel beta barrel core and a single alpha
      helix for binding the pyrophosphate of FAD. The NADP binding domain (residues 162
      to 314) has a central five-strand parallel beta sheet and six surrounding
      helices. Binding of the competitive inhibitor 2'-phospho-AMP (AMP, adenosine
      monophosphate) places the NADP binding site at the carboxyl-terminal edge of the
      sheet in a manner similar to the nucleotide binding of the dehydrogenase family.
      The structures reveal the key residues that function in cofactor binding and the
      catalytic center. With these key residues as a guide, conclusive evidence is
      presented that the ferredoxin reductase structure is a prototype for the
      nicotinamide dinucleotide and FAD binding domains of the enzymes NADPH-cytochrome
      P450 reductase, NADPH-sulfite reductase, NADH-cytochrome b5 reductase, and NADH
      nitrate reductase. Thus this structure provides a structural framework for the
      NADH- or NADPH-dependent flavoenzyme parts of five distinct enzymes involved in
      photosynthesis, in the assimilation of inorganic nitrogen and sulfur, in fatty
      acid oxidation, in the reduction of methemoglobin, and in the metabolism of many
      pesticides, drugs, and carcinogens.

PMID- 1986416
TI  - Cardiopulmonary resuscitation.

PMID- 1986415
TI  - Captopril-induced cholestatic jaundice.
AB  - I have reported a case of captopril-induced cholestatic jaundice. This drug is
      being used with increasing frequency, so it is important that physicians
      recognize this adverse effect. Captopril-induced jaundice resolves after
      cessation of captopril therapy.

PMID- 1986417
TI  - A measure of excessive "Reliance on high technology" (RHT) in medicine and what
      it means.

PMID- 1986418
TI  - Mammograms and ER in patients with breast cancer.

PMID- 1986419
TI  - Breast cancer detection.

PMID- 1986420
TI  - Alcohol and cocaine use among first-year college students.
AB  - We surveyed 1528 first-year students at the University of Virginia, 1 month after
      their arrival on campus, who had used alcohol at some time in their lives. Our
      survey was designed to identify alcohol and cocaine use, and related psychosocial
      patterns. Men drank more and more often than women. Our data suggest that body
      weight should be considered in defining those who drink heavily and often. We
      define 'frequent heavy drinking' as five or more drinks in a row each week for
      men and three to four drinks or more in a row each week for women. Frequent heavy
      drinkers, cocaine users, and students with psychosocial problems appeared
      disproportionately among students planning to join fraternities and sororities.
      Although first-year students used cocaine infrequently, its users followed the
      patterns of frequent heavy drinkers. We believe efforts to correct alcohol and
      cocaine misuse by college students should be directed, in part, at social
      organizations such as Greek-letter societies. Also, we must attend to
      psychosocial features that predispose to alcohol and cocaine misuse.

PMID- 1986421
TI  - Pharmacokinetic dosing of phenobarbital in the treatment of alcohol withdrawal
      syndrome.
AB  - We used a pharmacokinetically derived phenobarbital dosing protocol to treat
      alcohol withdrawal syndrome in patients admitted to a family medicine inpatient
      service. We describe the protocol and include two case reports documenting its
      efficacy. Although benzodiazepine agents are considered by many to be the primary
      agents of choice, based upon our experience and its ease of administration,
      relative safety, therapeutic efficacy, and lower cost, phenobarbital should be
      reconsidered as a promising alternative. Comparative trials between these two
      therapeutic classes will clarify their roles in the treatment of alcohol
      withdrawal syndrome.

PMID- 1986422
TI  - Inpatients with AIDS and AIDS-related complex: economic inpact on hospitals in
      North Carolina.
AB  - To determine the economic impact of acquired immunodeficiency syndrome (AIDS) or
      AIDS-related complex (ARC) cases on North Carolina hospitals, we collected
      inpatient data from all North Carolina hospitals on charges and number of
      patients discharged with these diagnoses. More than 97% of the state's hospitals
      responded to the survey for the study year (1987-1988). There were 540 AIDS/ARC
      discharges from 58 North Carolina general hospitals and 125 AIDS/ARC discharges
      from 13 other types of hospitals, for a statewide total of 665 patients. The
      total general hospital charges for AIDS/ARC inpatients in North Carolina were
      approximately $7.7 million per year, and almost $2 million of these charges were
      uncompensated by any insurance. The greatest burden of cost for this care was
      borne disproportionately by 15 of the 58 general hospitals, accounting for 82% of
      the discharges.

PMID- 1986424
TI  - There oughta be a law...

PMID- 1986425
TI  - Collagenous colitis: report of nine cases and review of the literature.
AB  - Collagenous colitis is characterized clinically by chronic watery diarrhea and
      pathologically by a distinctive band of collagen deposited below the colonic
      epithelium and an inflammatory cell infiltrate of the lamina propria. Since 1976,
      more than 100 cases have been described. We report an additional nine cases
      occurring in five women and four men ranging in age from 18 to 80 years. Diarrhea
      was present before diagnosis for 2 to 4 months in four cases and for 1 to 25
      years in another four cases. One patient did not have diarrhea. Results of
      radiologic and stool studies were normal in all cases. All patients had flexible
      sigmoidoscopy or colonoscopy. Microscopic examination of biopsy material was
      interpreted as characteristic of collagenous colitis. Two cases resolved with
      psyllium mucilloid therapy alone. Of the five patients treated with azulfidine,
      three had marked improvement, one had partial response, and one had no change.

PMID- 1986423
TI  - Indigenous cases of Lyme disease diagnosed in North Carolina.
AB  - Between January 1984 and December 1989, 102 indigenous cases of Lyme disease were
      reported in North Carolina. Lyme disease was reported in each of the three major
      geographic regions of the state: mountain, piedmont, and coastal plain. One or
      more diagnoses were made in 42 of 100 counties. Patients ranged in age from 5
      months to 78 years (median, 27 years); 58 patients (57%) reported a history of
      tick exposure within 1 month of the onset of symptoms. Erythema migrans was
      reported by 93 patients (91%). Arthritis (30%), neurologic symptoms (10%), and
      cardiac abnormalities (7%) were observed. Thirty of the 102 cases were confirmed
      serologically by indirect fluorescence microscopy or enzyme-linked immunosorbent
      assay.

PMID- 1986426
TI  - Intraoperative colonic lavage: failure to decrease mucosal microflora.
AB  - Few data exist concerning the ability of intraoperative colonic lavage to
      decrease colonic bacterial counts, and nothing is known about its effect on the
      recently described mucosa-associated bacteria. The goal of our study was to
      determine the impact of intraoperative colonic lavage on both the intraluminal
      and mucosal microflora. After intraoperative colonic washout in 10 adult male
      Sprague-Dawley rats, quantitative and qualitative aerobic and anaerobic cultures
      of the intraluminal and mucosal bacteria were obtained. Tissue was also removed
      for scanning electron microscopic examination of the colon wall. Whereas 1000
      fold to 10,000-fold reductions of aerobic and anaerobic intraluminal flora were
      achieved with mechanical lavage, reductions of aerobic or anaerobic mucosal
      bacteria were not significant. Failure to diminish bacterial colonization in this
      ecologic niche may be partly responsible for the persistently high infection rate
      after emergency colorectal surgery.

PMID- 1986427
TI  - Williams' vulvovaginoplasty after supralevator total pelvic exenteration.
AB  - Seven patients had delayed Williams' vulvovaginoplasty after supralevator total
      pelvic exenteration. Of the three patients who died of carcinoma of the cervix
      (at 2, 5, and 15 months after vulvovaginoplasty), the first died before having a
      chance to attempt intercourse, but the other two had reported intercourse on at
      least two occasions after the reconstruction. One of the patients described the
      experiences as neither pleasant nor unpleasant but stated that her husband seemed
      satisfied. The other patient described the experience as satisfactory to both
      herself and her husband. The remaining four patients are alive with no evidence
      of recurrent disease at 28, 42, 56, and 106 months after operation. Two of these
      patients have reported entirely satisfactory sexual relations approximating pre
      exenteration frequency, but the remaining two have not had sexual relations since
      surgery. Both give the main reason for this as lack of opportunity. The Williams'
      vulvovaginoplasty appears to be a reasonable alternative for vaginal
      reconstruction in patients who will have and especially who have had
      exenteration. To improve results, other methods of vaginal reconstruction should
      continue to be evaluated.

PMID- 1986428
TI  - Obstetric complications in young teenagers.
AB  - We compared pregnancy outcome in 286 teenaged primigravidas (less than or equal
      to 16 years old) and 267 adult primigravidas (21 to 25 years old) who had similar
      prenatal care, socioeconomic status, and racial balance. The incidence of preterm
      labor and delivery of a low birthweight infant was significantly higher in the
      teenagers. The incidence of preeclampsia was significantly higher in the adults.
      Cesarean delivery was not done more frequently in teenagers, nor was there a
      higher incidence of infants small for gestational age, anemia, and abnormal
      presentation in labor. The birthweight of infants of black teenagers was
      significantly lower than the birthweight of those of white teenagers, and overall
      birthweight was significantly lower in infants of teenagers than those of adults.
      Although prenatal care, socioeconomic factors, and racial balance were comparable
      for young teenagers and adults, teenagers were still at a significantly greater
      risk for delivery of smaller infants, preterm labor, and low birthweight infants.

PMID- 1986429
TI  - Subsubspecialization.

PMID- 1986430
TI  - Sick building syndrome.
AB  - "Sick building syndrome" (SBS) is one of the more colorful terms describing an
      increasingly common pattern of symptoms found among workers in modern office
      buildings. Core symptoms include lethargy, mucous membrane irritation, headache,
      eye irritation, and dry skin. To prompt a diagnosis of SBS, these otherwise
      common symptoms must be "excessively" reported and primarily "work-related." The
      World Health Organization now estimates that 30% of new or remodeled office
      buildings show signs of SBS, and that between 10% and 30% of the occupants of
      these buildings are affected by SBS. Despite such figures, SBS remains poorly
      researched and even more poorly understood. The following review provides the
      clinician an overview of SBS that will allow a more accurate differential
      diagnosis and will help to prevent the widespread suffering that can accrue when
      SBS is not quickly recognized.

PMID- 1986431
TI  - Flexible sigmoidoscopy as a screening procedure in rural patients.
AB  - In this study of flexible sigmoidoscopy as a screening procedure for rural,
      impoverished patients, 16% of asymptomatic patients who were screened by
      sigmoidoscopy and 23% of patients with a positive test for fecal occult blood
      were found to have a polyp or carcinoma. Flexible sigmoidoscopy appears to be an
      important part of the physical examination of patients older than 50. It is a
      test that can readily be done by primary care physicians in a rural setting.

PMID- 1986432
TI  - Cobb Pilcher, MD: a remarkable neurologic surgeon.

PMID- 1986433
TI  - Ernest Caulfield, MD, FAAP: the philosophic outlook and method of a pediatric
      historian.

PMID- 1986434
TI  - A survey of drinking patterns during medical school.
AB  - Several studies have documented the common use of alcohol among medical students
      and the significant fraction of students (7% to 17%) who show a pattern of
      alcohol abuse. Many authors have pointed out the implications of physician
      impairment due to alcoholism, presently estimated at about 10%. We surveyed 263
      junior and senior medical students, and our data support earlier surveys of the
      prevalence of alcohol abuse and indicate that students tend to drink less heavily
      and less frequently after entering medical school. The clinically proven CAGE
      questions used in the survey showed statistically significant associations
      between heavy or frequent drinking before and during medical school, but only
      4.2% of respondents indicated that school officials had asked whether they had a
      drinking or drug abuse problem. Given these findings, we suggest the routine
      administration of screening instruments to medical students, using education and
      minimal intervention strategies with individuals at risk.

PMID- 1986436
TI  - Rheumatoid arthritis of the larynx: the importance of early diagnosis and
      corticosteroid therapy.
AB  - Rheumatoid arthritis is a destructive systemic disorder characterized by
      remissions and exacerbations. The larynx is involved in approximately 25% of
      these patients. The importance of early detection of laryngeal involvement by
      this disease and treatment with corticosteroids has not been adequately addressed
      in the literature. We have described five patients who had early diagnosis and
      successful treatment with systemic corticosteroids and/or corticosteroid
      injection of the cricoarytenoid joint.

PMID- 1986435
TI  - Eosinophilic pneumonia associated with reaction to radiographic contrast medium.
AB  - We have described what we believe to be the first published case of a reaction to
      radiographic contrast medium followed by a diffuse eosinophilic pneumonia. This
      association seems to confirm what is know about the immunologic mechanisms of
      such reactions, and though further verification of causation is needed, we found
      it to be the most plausible explanation.

PMID- 1986437
TI  - Pancreatic carcinoma in an elderly woman with an organic affective disorder and
      AIDS delusion.
AB  - An elderly woman with symptoms of depression and an AIDS delusion was found also
      to have pancreatic carcinoma. I have discussed her case in conjunction with
      organic affective disorder, the evaluation of depression in the elderly, and
      suicide in the elderly.

PMID- 1986438
TI  - Orbital inflammatory disease associated with systemic lupus erythematosus.
AB  - Orbital inflammatory disease in a patient with systemic lupus erythematosus is
      rare and presents a diagnostic dilemma as well as a therapeutic challenge. Ours
      appears to be the sixth such case reported in the literature.

PMID- 1986439
TI  - South Africa and the World Health Organization.

PMID- 1986440
TI  - A comparative study of atenolol, nifedipine and their combination in the
      treatment of hypertension.
AB  - The antihypertensive effects, as assessed by clinical and ambulatory blood
      pressure measurement, of nifedipine slow-release (SR), atenolol and the two in
      combination were evaluated in 28 known hypertensives in a placebo-controlled,
      double-blind, randomised cross-over trial. Clinical blood pressure was
      significantly lower on combination therapy (P less than 0.025) than on either
      agent alone, although all therapeutic agents reduced blood pressure significantly
      when compared with placebo (P less than 0.01). All ambulatory blood pressure
      measurements obtained on any therapeutic agent were significantly lower than
      those obtained on placebo (P less than 0.01). The mean daytime (08h00-17h00)
      ambulatory blood pressure measurement as well as the percentage of this
      monitoring period during which patients were hypertensive were significantly
      lower (P less than 0.01) on combination therapy than on nifedipine SR. A similar
      pattern was observed for 24-hour ambulatory blood pressure measurements. Headache
      was the most significant adverse effect. This was most common with nifedipine SR,
      less common with combination therapy and least common with atenolol. Combination
      therapy with nifedipine SR and atenolol is therefore a viable therapeutic
      alternative in the treatment of patients with benign essential hypertension.

PMID- 1986441
TI  - Endoscopic retrograde cholangiopancreatography and endoscopic sphincterotomy in
      the management of suspected gallstone pancreatitis.
AB  - An approach to suspected gallstone pancreatitis based on endoscopic retrograde
      cholangiopancreatography (ERCP) and endoscopic sphincterotomy (ES) was adopted in
      1976 and was followed in 29 patients. ERCP became the routine method of early
      biliary tract assessment when gallstone pancreatitis was suspected on clinical
      and biochemical grounds, and further management was based on ERCP findings. If
      calculi were detected in the common bile duct (13 cases) ES was performed; when
      calculi were confined to the gallbladder (12 cases) cholecystectomy was advised;
      and if no calculi were detected on ERCP (4 cases) investigations were continued.
      ERCP proved to be a reliable guide to management, while ES provided safe and
      effective symptomatic relief when choledocholithiasis was present, and prevented
      recurrence of pancreatitis even when the gallbladder remained in situ.

PMID- 1986443
TI  - Multiple authorship.

PMID- 1986442
TI  - Cholangiography and endoscopic sphincterotomy in the management of severe acute
      gallstone pancreatitis discovered at diagnostic laparotomy.
AB  - Seven patients with gallstone pancreatitis discovered at diagnostic laparotomy
      did not undergo definitive biliary surgery because it was considered hazardous in
      the presence of severe acute pancreatitis. The procedures carried out at
      operation in these cases included cholecystectomy and T-tube drainage (2
      patients) cholecystostomy drainage (3 patients), and closure of the abdomen
      without drainage (2 patients). Direct cholangiography was carried out
      postoperatively in all cases. The biliary drain was used for this purpose in 5
      patients, and endoscopic retrograde cholangiopancreatography was performed in 2.
      All patients were found to have calculi in the common bile duct and were
      successfully managed by endoscopic sphincterotomy (ES) without complications or
      mortality. ES therefore appears to be a safe and effective method of avoiding
      difficult and hazardous biliary surgery in the presence of severe acute
      pancreatitis.

PMID- 1986445
TI  - Pituitary function tests in black patients with pseudocyesis.
AB  - Pituitary function was evaluated in a group of 10 patients with pseudocyesis. One
      patient was postmenopausal; the remainder demonstrated normal basal prolactin,
      luteinising hormone (LH) and follicle-stimulating hormone (FSH) levels and also
      normal pituitary-adrenal, pituitary-thyroid axes. Oestradiol deficiency was
      present in 6 patients, while 2 patients demonstrated elevated serum progesterone
      values, suggestive of a luteal phase. Gonadotrophin-releasing hormone
      administration resulted in exaggerated stimulation of LH and FSH in 4 and 2
      patients, respectively. Impaired growth hormone (GH) secretion was present in 6
      patients after insulin-induced hypoglycaemia and L-dopa administration. GH
      impairment is probably a consequence of the oestrogen deficiency that commonly
      occurs in this condition. It thus appears that there are aberrations in specific
      pituitary hormone responses after provocation in pseudocyesis.

PMID- 1986444
TI  - The value of percutaneous trephine biopsy in the diagnosis of lesions of the
      vertebral column.
AB  - The results obtained in 55 adult patients with sinister lesions of vertebral
      bodies, who were subjected to percutaneous trephine biopsy, are presented. A
      positive diagnosis was made on histopathological examination of specimens from 24
      patients (44%). In the remaining 31 patients (56%), pathological features were
      seen in 25, but no specific diagnosis was possible. There were 4 false-negative
      results. The lack of diagnostic specificity in a large proportion of the patients
      is explained by the fact that they presented at an advanced stage of disease
      (probably tuberculosis) when the process of healing had already started. In bony
      malignant conditions the results were very satisfactory. Percutaneous trephine
      biopsy is therefore a valuable diagnostic tool for positive diagnosis in a large
      proportion of patients with osseous lesions and for the exclusion of malignant
      disease.

PMID- 1986446
TI  - Measuring environmental health status in Oukasie, 1987.
AB  - This article reports on some aspects of the physical environment and on
      environmental health services at Oukasie. The data were collected over a weekend
      in August 1987 by an interview and by direct inspection of the environment using
      a standard schedule. We had a 100% response rate on the interviews. There was a
      mean of 2.2 +/- 1.6 persons per room in the households, with brick houses being
      less crowded than non-brick houses. Private yards were generally kept very clean.
      Bucket latrines were unhygienic and used by an average of 4 families. No latrine
      was built to accepted standards. Garbage collection and emptying of the bucket
      latrines by the municipality seemed to be unsatisfactory. Our overall impression
      was that where responsibility for maintenance of hygiene is either undefined,
      such as the collection chambers of bucket latrines, or a responsibility of the
      public authorities, such as garbage collection and water drainage, there is an
      unsatisfactory state of hygiene. Where maintenance of cleanliness is clearly a
      private responsibility, such as the maintenance of the cleanliness of private
      yards, the general status of hygiene is good.

PMID- 1986447
TI  - Community health survey of Oukasie, 1987.
AB  - A series of surveys were conducted at the request of the community of Oukasie to
      determine certain public health information in the township, a peri-urban black
      community. This article describes two of these surveys. The first, a census and
      partial demographic survey, showed that the total black population was around
      6,300 with a mean household occupancy of 4.1. Some of the estimated vital
      statistics calculated were an infant mortality rate of 36.6/1,000, a crude birth
      rate of 28.0/1,000, a crude death rate of 6.5/1,000, and a general fertility rate
      of 99.3/1,000. The second survey into the nutritional and immunisation status of
      children aged under 5 years showed that 20% of children were underweight and
      nearly half were incompletely immunised at 1 year of age. These studies,
      involving local community and student volunteers, were rapidly and inexpensively
      done and provide basic public health information.

PMID- 1986448
TI  - Effect of stress on birth weight in two Johannesburg populations.
AB  - The effect of stress on birth weight was assessed in mothers delivering at
      Johannesburg (predominantly white) and Baragwanath (exclusively black) Hospitals.
      The Social Readjustment Rating Scale of Holmes and Rahe was used to assign
      maternal stress scores established during an interview conducted within 36 hours
      of delivery. Only mothers without medical problems who had delivered liveborn
      infants were included. Maternal age, obstetric history, smoking history and
      stresses present during the 12 months preceding delivery were recorded. Of 535
      Johannesburg and 662 Baragwanath mothers studied, 48% and 55% respectively
      reported significant stresses. Analysis of the two groups revealed that for the
      Johannesburg mothers, smoking, cumulative stress score and previous preterm birth
      were important determinants of birth weight. Of the stress factors studied,
      marital separation and death of a spouse were significantly associated with a
      lower birth weight. For Baragwanath mothers the major determinants of low birth
      weight were maternal age, loss of income through being dismissed from work, or
      having to leave school as a consequence of the pregnancy.

PMID- 1986450
TI  - The need to democratise the health services--a challenge to doctors.

PMID- 1986451
TI  - Frail aged persons residing in South African homes for the aged who require
      hospitalisation. Part II. Rural areas.
AB  - The numbers and characteristics of white residents identified by medical and
      nursing staff to require more staff time and/or expertise and/or medical
      equipment than was available in rural homes for the aged in the Orange Free State
      were assessed. In the opinion of institution staff, 12.6% of extremely infirm
      aged persons would benefit by admission to a hospital catering for the
      chronically ill. The conditions affecting these residents are described and
      recommendations relating to their management are made.

PMID- 1986449
TI  - Frail aged persons residing in South African homes for the aged who require
      hospitalisation. Part I. Urban areas.
AB  - The numbers and characteristics of white residents identified by medical and
      nursing staff as requiring more staff time and/or expertise and/or medical
      equipment than is available in homes for the aged were assessed. Only 27 out of
      2,447 (1.1%) extremely infirm aged persons resident in 93 homes for the aged
      would, in the opinion of institutional staff, benefit by admission to a long-term
      care hospital catering for chronically ill. The conditions affecting these
      residents are described and recommendations relating to their management made.

PMID- 1986453
TI  - Planning for health.

PMID- 1986452
TI  - Correspondence with a pioneer, Jurgen Lehmann (1898-1989), producer of the first
      effective antituberculosis specific.
AB  - Correspondence between the author and Lehmann provided evidence that the latter
      evolved the first effective antituberculosis drug, para-aminosalicylic acid
      (PAS), contrary to accepted belief that this honour belonged to Nobel Prize
      winner Selman A. Waksman for his production of streptomycin. While both drugs
      appeared in 1943, successful animal and clinical trials of PAS preceded those of
      streptomycin. PAS has been discarded in modern treatment regimens because of
      gastric side-effects, but was available at a critical time to demonstrate the
      principle of multiple therapy in prevention of bacterial resistance in
      tuberculosis therapy. It probably saved streptomycin, which causes bacterial
      resistance and clinical regression within 3 months when used alone, from being
      discarded as an unsuitable drug of temporary benefit and a public health hazard.

PMID- 1986454
TI  - Mercury intoxication as a result of illicit gold smelting.

PMID- 1986455
TI  - Bone properties of osteoporotic patients with femoral neck fractures.

PMID- 1986456
TI  - Naloxone in opiate-induced colonic pseudo-obstruction.

PMID- 1986458
TI  - Founder effect in 20 Afrikaner kindreds with pseudoxanthoma elasticum.
AB  - The pedigrees of 20 families with pseudoxanthoma elasticum (PXE) were
      investigated. The analyses involved 13 generations up to and including the
      initial settlers, who arrived in the Cape before 1660. Four settler surnames
      predominate in these pedigrees. Because of the marriage patterns of the settlers'
      descendants it was necessary to classify the four surnames into two groups. It is
      suggested that these two groups are the founder groups of present-day PXE
      patients. Similar genealogical studies have been performed on kindreds with
      familial polyposis, familial heart block and familial hypercholesterolaemia,
      among other disorders. Due to geographical isolation, political developments and
      cultural factors in the Afrikaner, these investigations are feasible and often
      lead to the identification of founder origin.

PMID- 1986457
TI  - Findings on computed tomography of the chest in lymphangiomyomatosis.

PMID- 1986459
TI  - Improving the quality of stored platelets.

PMID- 1986460
TI  - Red cell use during cesarean delivery.
AB  - The transfusion of red cells (RBCs) was analyzed over a 4-year period (1984
      1987), during which 9596 cesarean deliveries were performed. A total of 336
      patients were identified as receiving RBC transfusions during or after cesarean
      delivery; 747 units of RBCs were administered. The overall incidence of
      transfusion in this patient population declined from 6.2 to 3.2 percent during
      the study period (p less than 0.001). Slightly more than one-half (54.4%) of all
      transfusions were given in the operating room or recovery room. The majority of
      patients (68.4%) received 2 units of RBCs, 11.6 percent received a 1-unit
      transfusion, and 8.3 percent received 5 units or more. The most common obstetric
      diagnoses associated with RBC transfusion were disorders of placental
      implantation, preeclampsia, premature labor with tocolytic therapy, fetal
      distress, and augmentation of dysfunctional labor. In patients without risk
      factors for bleeding, there was no trend indicating increased transfusion
      requirements when general anesthesia was employed. In conclusion, this study
      documents a decline in the transfusion rate during cesarean delivery.

PMID- 1986462
TI  - Risk of human immunodeficiency virus (HIV) transmission by blood transfusions
      before the implementation of HIV-1 antibody screening. The Transfusion Safety
      Study Group.
AB  - Little information is available regarding the risk of human immunodeficiency
      virus type 1 (HIV-1) infection for patients transfused before routine anti-HIV-1
      screening of blood donors was instituted in March 1985. A model was developed for
      estimating both the proportion and the number of transfusion recipients in the
      San Francisco Bay area who were infected by HIV-1 during each of the 7 years
      preceding routine donor screening for anti-HIV-1. The model is based on analysis
      of 1) donation histories of HIV-1-infected donors identified at the regional
      blood center; 2) HIV-1 seroprevalence estimates for homosexual and bisexual men
      in San Francisco; and 3) HIV-1 infection and survival rates for recipients traced
      by the Transfusion Safety Study and Irwin Memorial Blood Centers' Look Back
      Program. The incidence of transfusion-associated HIV-1 infection is estimated to
      have risen rapidly from the first occurrence in 1978 to a peak in late 1982 of
      approximately 1.1 percent per transfused unit. The decrease after 1982 coincided
      with the implementation of high-risk donor deferral measures. It is estimated
      that, overall, approximately 2135 transfusion recipients were infected with HIV-1
      in the San Francisco region alone. This number suggests a higher prevalence of
      transfusion-associated HIV-1 infection than has been generally recognized and
      indicates the need for continued tracing of potentially exposed recipients. The
      data also strongly support the effectiveness of early donor education and self
      exclusion measures and emphasize the importance of continued research and
      development in this area.

PMID- 1986461
TI  - Platelet storage in synthetic media lacking glucose and bicarbonate.
AB  - The goal of these studies was to develop a cost-effective medium for the storage
      at 22 +/- 2 degrees C of platelets for transfusion. Platelet concentrates were
      prepared from platelet-rich plasma in a standard fashion and resuspended in 55 mL
      of medium. Residual plasma was 14.4 +/- 4.3 percent of the final suspending
      solution. The use of a simple solution containing electrolytes and citrate, but
      no glucose or bicarbonate, was associated with a drop in pH to the range of 6.0
      to 6.6, as a result of the production of lactic acid from the platelet glycogen
      and glucose present in residual plasma. When 25 mM (25 mmol/L) sodium phosphate
      was included as a buffer, the drop in pH was retarded, but the range throughout
      storage was still 6.5 to 6.8. Nonetheless, platelets stored for 5 days in this
      phosphate-containing medium showed satisfactory maintenance of many in vitro
      variables. However, there was a 10 to 35 percent reduction of in vivo recovery
      after isotopic labeling. There was no significant reduction in subsequent mean
      cell life. Because of the in vivo abnormalities, these media are not recommended
      for use at the present time. However, the results are encouraging and suggest
      that further research may lead to a satisfactory, cost-effective medium.

PMID- 1986463
TI  - Histologic and immunohistochemical studies on the preparation of white cell-poor
      red cell concentrates: the filtration process using three different polyester
      filters.
AB  - Three third-generation white cell (WBC)-depletion filters based on polyester
      layers with decreasing pore size were investigated. In the coarse layers,
      unaggregated granulocytes, monocytes, and platelets and aggregates of these cells
      were captured in close contact with the fibers. This indicates that the depletion
      of granulocytes, monocytes, and platelets in the coarse layers of the filters is
      due in part to activation and adhesion with the formation of cell clusters on the
      fibers. In Filter I and Filter II platelets were not found in the fine layers,
      whereas in Filter III, 70 percent of the platelets were detected as unaggregated
      platelets on the fibers of the fine layers. More than 95 percent of the
      lymphocytes captured in the three filters occurred as single cells in the fine
      layers, and over 60 percent of these could be recovered. This suggests that the
      depletion of lymphocytes depended on trapping of the cells in the fiber network.
      All three filters captured HLA-DR-positive lymphocytes in the top layers, a
      finding that supports earlier reports that the transfusion of filtered red cell
      concentrates reduces HLA alloimmunization. More lymphocytes and granulocytes were
      found in the last layer of Filters II and III than of Filter I. Therefore, the
      risk of white cell leakage is probably lowest for Filter I. Red cells were found
      as red cell aggregates in the fine layers of Filters I and II, whereas almost no
      red cells were detected in Filter III. It was shown that the three filters
      studied were similar in their removal of WBCs, but differed in their mechanisms
      of removal.

PMID- 1986464
TI  - The low-incidence red cell antigen Wra: genetic studies.
AB  - Studies of 91 individuals in three families allowed a genetic-linkage analysis of
      the gene governing the production of the low-incidence red cell antigen Wra and
      provided evidence that Wra is not a member of the Scianna, Landsteiner-Wiener,
      Chido/Rodgers, or XK blood group systems, and that the "WR" locus is excluded
      from autosomal sites or regions 1p34-p22.1, 1p21-q23, 1q32, 2p25, 3q21, 4q28-q32,
      6p24-q12, 9q34.1-q34.2, 13q14.1-q14.2, 14q24.3-q32.1, 14q32.33, 16p13, 16q22.1,
      and 21q21-q22.1. "WR" is also excluded from within specified genetic distances of
      chromosomes 8 (GPT), 18 (JK), 19 (C3), 20 (ADA), and 22 (P1) loci, which brings
      its exclusion to approximately 10 percent (320cM) of the total genetic map of the
      genome. The possibility that "WR" is pseudoautosomal is deemed to be highly
      unlikely.

PMID- 1986465
TI  - Evaluation of pediatric transfusion practice using criteria maps.
AB  - Pediatric blood transfusion practice in a tertiary-care pediatric hospital was
      evaluated retrospectively by using the technique of criteria mapping. A total of
      630 transfusion episodes involving red cell concentrates, frozen plasma (plasma
      frozen within 24 hours of collection), platelet concentrates, and albumin were
      reviewed: 243 (86.2%) were reviewed only by a technical assistant, and 87 (13.8%)
      required additional physician review. Of these, 138 were red cell concentrate
      transfusions: 79.7 percent of that group were considered appropriate, 11.6
      percent of unknown benefit/risk ratio, 5.8 percent inappropriate, and 2.9 percent
      impossible to evaluate. Some 246 frozen plasma transfusions were reviewed: 42.3
      percent were considered appropriate, 32.5 percent of unknown benefit/risk ratio,
      17.5 percent inappropriate, and 7.7 percent impossible to evaluate. A total of
      139 platelet concentrate transfusions were reviewed: 64.7 percent were considered
      appropriate, 16.5 percent of unknown benefit/risk ratio, 10.1 percent
      inappropriate, and 8.6 percent impossible to evaluate. Some 107 albumin
      transfusions were reviewed: 90.6 percent were considered appropriate, 1.9 percent
      inappropriate, and 7.5 percent impossible to evaluate. The criteria maps
      developed for this study were easy for the technical assistant to use, and areas
      of appropriate and inappropriate pediatric transfusion practice were clearly
      identified.

PMID- 1986466
TI  - Physiologic observations of pregnant women undergoing prophylactic
      erythrocytapheresis for sickle cell disease.
AB  - Five women in the second or early third trimester of pregnancy underwent
      prophylactic partial red cell exchange by automated erythrocytapheresis for
      sickle cell disease. The purpose of this pilot study was to characterize the
      hematologic, hemodynamic, and metabolic changes associated with this procedure.
      Pretransfusion hematocrit increased 49 percent by 3 to 5 days after the
      transfusion. Paired observations indicate a 14-percent drop in maternal oxygen
      consumption. There was a slight tendency for reduced posttransfusion cardiac
      output that resulted primarily from changes in maternal heart rate and not from
      changes in stroke volume. Left ventricular contractility also tended to decrease
      after transfusion. Neither fetal bradycardia nor alteration in the umbilical
      circulation by Doppler ultrasound was observed during the transfusion procedures.
      Despite substantial hematologic alterations, this procedure is associated with
      small or negligible changes in maternal hemodynamic and metabolic function for
      minimally symptomatic pregnant patients with sickle cell disease.

PMID- 1986467
TI  - The epidemiology of the human T-cell lymphotrophic virus type I and type II:
      etiologic role in human disease.

PMID- 1986468
TI  - Red cell antibodies arising from solid organ transplants.
AB  - RBC antibodies arising from transplanted organs and directed against recipient
      RBCs represent a well-established immunohematologic complication of solid organ
      transplantation. In ABO-unmatched organs, the frequency and severity of graft
      antibodies and hemolysis generally increase with the size (lymphoid content) of
      the organ, from kidney to liver to heart-lung transplants. In the cases reviewed
      here, the frequency of hemolysis increased in cyclosporine-treated kidney
      transplant recipients and O-to-A liver transplant recipients and decreased in
      group AB liver transplant recipients and kidney transplant recipients receiving
      azathioprine or low-dose postoperative graft irradiation. Available data cannot
      otherwise distinguish which cyclosporine-treated recipients of ABO-unmatched
      kidneys and livers (30-40% of total) will develop graft antibody. There has been
      no conclusive effect to date of the age, race, or gender of the donor or the
      recipient, of cadaver versus living kidney donors, or of patients' A2 or secretor
      status. In a few cases of living-donor kidney grafts, the donor was the patient's
      mother or wife who had been exposed to the recipient's RBC antigens via
      pregnancy. The ABO antibodies are typically IgG, appear 7 to 10 days after
      transplantation, and last for about a month. If immediate-spin crossmatching is
      done routinely, DATs are recommended in compatibility testing after ABO-unmatched
      transplants. Changes in the immunosuppressive regimen, such as a change from
      cyclosporine therapy, have not affected the duration of these antibodies. Most
      patients require only transfusions for this self-limited process, but six cases
      of hemolysis-induced acute renal failure have been reported, and one death was
      attributed to complications of hemolysis. RBC or plasma exchange has been
      performed in a few fulminant cases. RBCs of the donor's blood type are given when
      antibody appears. Some workers recommend such transfusion as prophylaxis at the
      time of surgery, although in liver transplants, the plasma accompanying a large
      amount of group O RBCs given perioperatively might be problematic. In several
      other centers, ABO-unmatched liver transplants have equivalent overall graft
      survivals, but the Pittsburgh adult patients with hemolysis have had reduced
      early graft survival. In the cases reviewed here, nine IgG Rh antibodies from
      kidney grafts directed against recipient RBCs have been observed, usually
      beginning 2 to 3 weeks after a cyclosporine-treated transplant, lasting for 2 to
      6 months after operation, and causing mild hemolysis. One case represented a
      primary immune response from a previously unsensitized donor.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 1986469
TI  - Transurethral resection versus needle biopsy prior to radical prostatectomy for
      stage C prostate cancer. Influence on progression and survival.
AB  - Previous reports have claimed that transurethral resection of the prostate (TURP)
      preceding definitive radiation therapy for patients with Stage C prostate cancer
      promotes the risk of distant metastasis and increases the mortality rate. A total
      of 490 patients with pathologic Stage C adenocarcinoma of the prostate treated by
      radical prostatectomy were studied. Median time to follow-up was 4.6 years.
      Comparison was made between patients who had TURP within the six months preceding
      prostatectomy (n = 54) and those who had needle biopsy (n = 437) prior to
      operation. No significant differences were noted in local recurrence of disease,
      systemic progression of disease, disease-free interval, and overall and cause
      specific survival, even after adjustment for clinical (adjuvant treatment) and
      pathologic prognostic variables. Our data suggest that for patients with
      pathologic Stage C prostate cancer treated by radical surgery, preoperative TURP
      is not associated with unfavorable outcome.

PMID- 1986470
TI  - Treatment of unstable bladder.
AB  - We present our experience with 2 spinal-injury patients tested for urinary
      incontinence via implanted sacral nerve electrodes. In each patient, spinal
      injury occurred at the T-12 level, with presentation of spontaneous detrusor
      activity. Associated weakness of the voluntary sphincter mechanism was evident
      urodynamically. Neurostimulation via wire electrode in the S3 foramen produced
      good sphincter closure. Voiding secondary to spontaneous detrusor triggering
      could thereby be suppressed, eliminating embarrassing incontinence without
      interfering with the patient's ability to empty the bladder at regular intervals.
      The therapeutic principles of neurostimulation applicable to patients with
      spastic bladders are underscored by these 2 cases.

PMID- 1986471
TI  - Effect of ileal conduit on patients' activities following radical cystectomy.
AB  - Over the last twenty months, 110 patients who have undergone a radical cystectomy
      for bladder cancer at The University of Texas M. D. Anderson Cancer Center were
      surveyed to assess the effect of an ileal conduit urinary diversion on
      postoperative activity. Postoperatively, 47.3 percent of the patients were very
      active, 34.5 percent were moderately active, and 18.2 percent were sedentary.
      Chemotherapy and the patient's gender were found to have a statistically
      significant effect on postoperative activity level. Chemotherapy resulted in a
      decrease of very active patients from 55.6 percent to 27.9 percent and an
      increase in sedentary patients from 11.2 percent to 30.2 percent (P = 0.005). No
      difference in activity levels was seen in 73.9 percent of the nonchemotherapy
      patients. Fifty-one percent of the men were very active as compared with only
      19.1 percent of the women, whereas 20 percent more women than men were moderately
      active and 13 percent more were sedentary. Our experience indicates that the
      ileal conduit had no significant negative effect on activity if the effects of
      chemotherapy are controlled: 82.6 percent of the patients not receiving
      chemotherapy experienced either no change or an increase in their activity.

PMID- 1986472
TI  - Transverse colon-gastric tube composite reservoir.
AB  - We describe our technique for a new form of continent urinary diversion. This
      reservoir includes a detubularized segment of transverse colon to provide low
      pressure urine storage, tunneled ureteral reimplants to prevent reflux, and a
      tubularized gastric segment used as a continent catheterizable efferent limb.
      This technique provides a new option for continent diversion in a variety of
      patients.

PMID- 1986473
TI  - Cecal tubularization: lengthening technique for creation of catheterizable
      conduit.
AB  - The creation of a continent, catherizable stoma is an integral component of
      successful continent urinary diversion. A technique is described which allows
      lengthening of a continent appendicovesicostomy. This technique extends the
      applications for the Mitrofanoff principle of urinary tract reconstruction.

PMID- 1986474
TI  - Use of biofeedback in treatment of psychogenic voiding dysfunction.
AB  - A young man with psychologic problems and a long history of social inadequacy
      presented with voiding dysfunction. Videocystometrography revealed a normal
      filling phase and normal initiation of voiding interrupted by considerable
      straining by the patient and marked sphincter electromyographic (EMG) activity.
      Temporary amelioration was achieved by infiltration of the sphincter with
      lignocaine hydrochloride and by biofeedback therapy. In such cases optimal
      results are expected from long-term behavioral therapy.

PMID- 1986475
TI  - Renal cell carcinoma vs. renal oncocytoma. Report of a case with overlap features
      and review of the literature.
AB  - Although the salient features of renal oncocytomas and renal cell carcinomas have
      been discussed in the recent literature, renal masses with features of both
      entities will present diagnostic difficulty, especially when the cells are
      diffusely eosinophilic on microscopic examination. A case of a firm, tan, rounded
      mass replacing the lower pole of the kidney is discussed. The final diagnosis of
      renal cell carcinoma, granular cell type, was made after multiple sections of the
      tumor were examined, and after electron microscopy was performed. A thorough
      search by light microscopy should be made for clear cell foci, necrosis, mitotic
      activity, and vascular or capsular invasion, features generally accepted as
      pathognomonic for renal cell carcinoma. Cellular and especially nuclear
      pleomorphism is typically focal or mild in renal oncocytomas. True oncocytic
      tumors will be packed with mitochondria on electron microscopy; however, granular
      renal cell carcinomas will contain mitochondria as well as other cellular
      organelles, lipid, and glycogen. Electron microscopy should be performed on
      tumors suspected of being oncocytomas because eosinophilia on hematoxylin and
      eosin stain, as demonstrated by this case, is not a predictable measure of
      mitochondria content. Immunoperoxidase staining for vimentin in oncocytomas has
      recently been shown to be negative, and may offer a method of ruling out
      oncocytoma in vimentin-positive tumors, pending further studies.

PMID- 1986476
TI  - Treatment of renal transplant stones by extracorporeal shock-wave lithotripsy in
      the prone position.
AB  - Two patients with renal transplant lithiasis were successfully treated with
      extracorporeal shock-wave lithotripsy (ESWL) in the prone position. Pathogenesis
      and treatment of transplant lithiasis are discussed. Performing ESWL on renal
      transplant patients in the prone position has advantages over standard
      positioning techniques.

PMID- 1986477
TI  - Anal submucosal injection: a new route for drug administration. VI. Chronic
      prostatitis: a new modality of treatment with report of eleven cases.
AB  - The anal submucosal route was used for the treatment of chronic bacterial
      prostatitis in 11 patients. Prior to presentation, the patients had received
      different antimicrobial agents; the symptoms disappeared only to recur whenever
      the drug was discontinued. After repeated failure, the patients were treated with
      gentamicin to which the organisms were sensitive, via the anal submucosal route.
      A daily injection was given for ten days on an outpatient basis. The technique of
      injection is described. The patients were followed up clinically and by segmented
      cultures for three years. No anorectal complications were encountered as had been
      demonstrated experimentally. The symptoms of chronic prostatitis disappeared, and
      culture was negative by the end of treatment and for two to three years
      thereafter in all patients. It appears that the antimicrobial agent, via anal
      route, reaches the prostatic tissues at a higher concentration than that of the
      serum. The route adopted by the drug to reach the prostate from the anal
      submucosa is presented.

PMID- 1986479
TI  - Intraoperative percutaneous gastrostomy for routine use in major urologic
      surgery.

PMID- 1986478
TI  - Eosinophilic granuloma of bladder.
AB  - Eosinophilic granuloma of the bladder, a rare and certainly poorly known disease,
      simulates bladder neoplasms. Clinical aspects, histology, and therapy in a young
      boy are described.

PMID- 1986480
TI  - Intracapsular testicular prosthesis.

PMID- 1986481
TI  - Study of antireflux nipple valves of Kock ileal urinary reservoir. Experimental
      investigation in dogs.
AB  - To better assess the construction, maintenance, and function of the Kock ileal
      urinary reservoir with its continent antirefluxing nipple valves, laboratory
      investigations in dogs were done simultaneously with clinical trials in humans in
      1983. Fifteen dogs underwent creation of hemi-Kock ileal reservoirs (without the
      efferent valve and limb) that were anastomosed to their bladders as
      enterocystoplasties. The afferent antirefluxing nipple valves were intussuscepted
      after 7 cm of underlying mesentery had been removed. The nipples were further
      stabilized with metal and absorbable (Polysorb) staples and Marlex collars. The
      right ureters were anastomosed to the afferent limb of the reservoirs with the
      contralateral systems left intact as controls. Ten dogs were able to be followed
      at the vivaria for twelve to thirty-six months and then studied. All nipple
      valves remained intact, viable, and nonrefluxing without revision. All kidneys
      remained histologically normal except those in dogs with dilated ureters
      secondary to ureteroileal stenosis with concurrent calculi formation. Calculi
      formed on exposed metal staples and Marlex. The absorbable staples were found to
      promote appropriate healing and were never the nidus for stone formation. It
      appears that the intussuscepted nipple valve (with its mesentery removed) is
      reproducible and functionally reliable in preventing reflux. It also appears
      these valves can histologically preserve diverted kidneys if the upper urinary
      tract drainage is normal and calculi are minimized. The proper placement of
      staples and the elimination of Marlex-anchoring collars are indicated to minimize
      calculi.

PMID- 1986482
TI  - Measles returns.

PMID- 1986483
TI  - The painful shoulder: Part I. Extrinsic disorders.
AB  - Shoulder disorders are most commonly manifested by pain and limited function.
      Careful history and examination help the physician localize the problem to the
      shoulder joint, the surrounding tissues or adjacent sites that can cause referred
      pain to the shoulder. Common extrinsic causes of shoulder pain include postural
      problems and cervical spine disorders.

PMID- 1986484
TI  - The radiographic spectrum of renal osteodystrophy.
AB  - Chronic renal failure often results in bone changes, collectively known as renal
      osteodystrophy. These changes include osteitis fibrosa, osteosclerosis, soft
      tissue calcifications, osteomalacia (in adults) and rickets (in children). Early
      recognition of renal osteodystrophy allows more aggressive clinical control of
      serum calcium and phosphate levels. Intervention may spare the patient late
      complications such as fractures, pain and loss of skeletal function.

PMID- 1986485
TI  - Psychostimulants for depression in the medically ill.
AB  - Medically ill patients who show signs of depression may have problems with
      traditional antidepressant therapy, because of the side effect profile and the
      delayed onset of action of these agents. Psychostimulants such as methylphenidate
      and dextroamphetamine are another treatment option. The beneficial effects of
      these drugs are usually noted within 36 hours, and drug habituation is generally
      not a problem. The primary obstacle to the use of these agents for depression in
      medically ill patients is the hesitancy of physicians to prescribe them.

PMID- 1986486
TI  - Spontaneous abortion.
AB  - Spontaneous abortion, or the early termination of pregnancy without outside
      interference, may be caused by fetal, maternal or external factors. In many
      cases, a specific etiology may never be identified. A variety of clinical
      presentations are possible, ranging from imperceptible loss to profound life
      threatening shock. Physicians should be able to diagnose and manage the six
      recognized types of spontaneous abortion: threatened, inevitable, incomplete,
      complete, missed and septic. In all cases, uterine evacuation, avoidance of
      complications and psychologic support of the family are important. The prognosis
      for a subsequent successful pregnancy is good, except in cases of habitual
      abortion.

PMID- 1986487
TI  - Chronic upper lobe cavitary lung disease.
AB  - Chronic upper lobe cavitary lung disease may be caused by infections, emphysema,
      cystic fibrosis, lung cancer, sarcoidosis and rheumatologic syndromes. The
      diagnostic evaluation includes a complete history, a physical examination, a
      chest radiograph, and sputum examination and culture. In some cases, computed
      tomographic scanning and biopsy are required.

PMID- 1986488
TI  - Antiviral drug therapy.
AB  - Major advances in molecular virology have led to the development of new antiviral
      compounds. These drugs include ribavirin, used in the treatment of severe
      respiratory syncytial virus infection in children; amantadine, used in the
      prophylaxis and treatment of influenza A infection; acyclovir, used in a variety
      of herpesvirus infections, including primary gingivostomatitis, genital herpes
      and herpes zoster; ganciclovir, used in the treatment of retinitis due to
      cytomegalovirus, and zidovudine, used in the prophylaxis and treatment of human
      immunodeficiency virus infection.

PMID- 1986490
TI  - When did you grow old, Charles?

PMID- 1986489
TI  - Ketorolac: an injectable NSAID.
AB  - Ketorolac tromethamine is the first injectable nonsteroidal anti-inflammatory
      drug approved for the management of acute pain. In analgesic potency and ability
      to relieve postoperative pain, it is comparable to morphine. The advantages of
      ketorolac over opiates are the absence of respiratory depression and lack of drug
      abuse potential. Ketorolac has a longer duration of action than morphine, but it
      has less effect on the central nervous system. Ketorolac should not be used for
      obstetric analgesia.

PMID- 1986492
TI  - Medical hazardous and toxic waste.

PMID- 1986493
TI  - Thrombolytic therapy and gastrointestinal bleeding.

PMID- 1986491
TI  - Using inhalers correctly.

PMID- 1986494
TI  - Predictors of long-term cardiac survival in patients with multivessel coronary
      artery disease undergoing percutaneous transluminal coronary angioplasty.
AB  - The predictors of 5-year cardiac survival in patients with multivessel coronary
      artery disease (CAD) undergoing percutaneous transluminal coronary angioplasty
      (PTCA) were analyzed in a series of 637 consecutive patients. The average age was
      59 +/- 11 years in 472 men and 165 women. Diabetes mellitus, previous myocardial
      infarction and unstable angina were present in 119 (19%), 261 (41%) and 305 (47%)
      patients, respectively. Angiographically, 460 patients had 2-vessel and 177
      patients had 3-vessel CAD. The left ventricular contraction score was greater
      than or equal to 12 in 55 patients. Angiographic success (less than 50% residual
      stenosis) was achieved in 85% of the 1,343 narrowings and clinical success was
      obtained in 526 (83%) of the 637 patients. Complete revascularization was
      obtained in 177 (34%) of 526 successful patients. Procedure-related complications
      resulted in death in 9 patients (1.4%), in Q-wave myocardial infarction only in 6
      patients (0.9%) and in emergency bypass surgery in 44 patients (6.9%) (of whom 10
      had Q-wave myocardial infarction). Follow-up for greater than or equal to 1 year
      and up to 6 years after PTCA was obtained in 608 (95%) of the 637 patients. To
      determine the predictors of 5-year cardiac survival, 28 clinical, angiographic
      and procedural variables were analyzed by Cox proportional-hazards regression.
      The estimated 5-year survival after PTCA was 88 +/- 2% in successful patients and
      77 +/- 5% in patients in whom PTCA was unsuccessful (p less than 0.001). When
      clinical success was forced into the Cox regression, the left ventricular
      contraction score of greater than or equal to 12, diabetes mellitus and age
      greater than or equal to 65 years showed additional adverse effects on
      survival.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1986495
TI  - Physiologic neuroendocrine arousal by mental arithmetic stress test in healthy
      subjects.

PMID- 1986496
TI  - Dynamic coronary ostial obstruction due to papillary fibroelastoma leading to
      myocardial ischemia and infarction.

PMID- 1986497
TI  - Severity of single-vessel coronary arterial stenosis and duration of angina as
      determinants of recruitable collateral vessels during balloon angioplasty
      occlusion.
AB  - To determine the factors that influence the presence of collateral vessels during
      coronary occlusion, we performed standardized contrast injection of the
      contralateral coronary artery in 58 consecutive patients, without previous
      myocardial infarction, undergoing percutaneous transluminal coronary angioplasty
      for 1-vessel disease (left anterior descending artery in 45, right coronary
      artery: in 10 and left circumflex artery in 3). The presence of collateral
      vessels during coronary occlusion, defined as partial or complete epicardial
      opacification by collateral vessels of the vessel dilated, was related to
      clinical, angiographic and electrocardiographic parameters. The angiographic
      appearance of collateral vessels during balloon inflation showed a weak, although
      statistically significant, correlation to the percent diameter stenosis before
      angioplasty (r = 0.28; p = 0.03) and the duration of angina (r = 0.37; p =
      0.004). By combining lesion severity with the duration of angina, collateral
      vessels during coronary occlusion were particularly related to a lesion severity
      greater than or equal to 70% and duration of angina greater than or equal to 3
      months (p less than 0.001). Furthermore, the presence of collateral vessels was
      associated with an absence of ST-segment shift (greater than or equal to 1 mm)
      during 1 minute of coronary occlusion (p less than 0.001).

PMID- 1986498
TI  - Characteristics of black patients admitted to coronary care units in metropolitan
      Seattle: results from the Myocardial Infarction Triage and Intervention Registry
      (MITI).
AB  - Since 1988, 641 black and 11,892 white patients with chest pain of presumed
      cardiac origin have been admitted to coronary care units in 19 hospitals in
      metropolitan Seattle. Black men and women were younger (58 vs 66, p less than
      0.0001), more often admitted to central city hospitals (p less than 0.0001), and
      developed evidence of acute myocardial infarction (AMI) less often (19 vs 23%, p
      = 0.01). In the subset of 2,870 AMI patients, blacks (n = 121) were younger (59
      vs 67, p less than 0.0001) and had less prior coronary artery bypass graft
      surgery (2 vs 10%, p = 0.005) and more prior hypertension (67 vs 46%, p less than
      0.0001). During hospitalization, whites (n = 2,749) had higher rates of coronary
      angioplasty (18 vs 10%, p = 0.03) and coronary artery bypass graft surgery (10 vs
      4%, p = 0.04), although thrombolytic therapy and cardiac catheterization were
      used equally in the 2 groups. Hospital mortality was 7.4% for black and 13.1% for
      white patients (p = 0.07). However, after adjustment for key demographic and
      clinical variables by logistic regression, this difference was not as apparent (p
      = 0.38). Questions about the premature onset of coronary artery disease, excess
      systemic hypertension, and the differential use of interventions in black persons
      have been raised by other investigators. Despite differences in age, referral
      patterns and the use of coronary angioplasty and bypass surgery, black and white
      patients with AMI in metropolitan Seattle had similar outcomes.

PMID- 1986499
TI  - Late results of 200 repeat coronary artery bypass operations.
AB  - To determine the clinical outcome and the long-term results of a second coronary
      artery bypass operation, we studied preoperative clinical status and
      catheterization data in 200 consecutive patients over a 9-year period (1979 to
      1987) (mean follow up time 34 months, maximum 120). The study group included 169
      men and 31 women (mean age 58.4 years [7% greater than 70 years]). Sixty-four
      percent of patients had severe angina (New York Heart Association class IV), 70%
      had 3-vessel coronary artery disease and 21% had poor left ventricular function.
      Reoperation was performed after a mean interval of 58 months after the first
      procedure. A mean of 3.3 distal anastomoses was placed. The operative mortality
      rate (30 days) was 7.5%, with additional cardiac morbidity (myocardial
      infarction, heart failure) in 11.5% of patients. Multivariate analysis showed an
      increased risk in women (risk ratio 3.6) and in patients with poor left
      ventricular function (risk ratio 3.1). The cumulative 5-year survival rate was
      estimated at 84%, with a rate of 77% for patients with poor left ventricular
      function (difference not significant). The probability of remaining free of a
      cardiac-related event (myocardial infarction, angioplasty, third operation,
      cardiac death) was 64% for 5 years. At the end of follow-up, 79% of the surviving
      patients were in New York Heart Association class I or II and nearly 50% of
      patients in the fifth year after the reoperation had good functional status. It
      is concluded that a reoperation is effective but carries an increased, immediate,
      operative risk.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1986500
TI  - Cardiovascular risk factor clustering and ratio of total cholesterol to high
      density lipoprotein cholesterol in angiographically documented coronary artery
      disease.
AB  - High levels of cardiac risk factors tend to cluster together and act
      synergistically. To develop a suitable and practical marker for clustering, we
      evaluated 380 consecutive patients at the time of coronary angiography. Analyses
      of lipid, rheologic, clinical and arteriographic profiles indicated a variety of
      interwoven relations. Because the ratio of total cholesterol to high-density
      lipoprotein (HDL) cholesterol (total/HDL cholesterol) was closely related to both
      the presence and extent of greater than or equal to 50% diameter reduction of
      greater than or equal to 1 coronary arteries, it was used to divide patients into
      quartiles. Clustering of high- and low-level risk factors was demonstrated in the
      highest and lowest quartiles of total/HDL cholesterol, respectively (p less than
      0.001). The highest quartile may be characterized by an only moderately elevated
      total cholesterol level but patients in this quartile may have a very low HDL
      cholesterol level, high triglycerides, a tendency toward high hemoglobin and
      fibrinogen levels, a history of smoking, previous myocardial infarction and
      multivessel disease. These results suggest that total/HDL cholesterol serves as a
      marker not only for obstructive coronary disease but also for a cluster of
      potentially modifiable risk factors.

PMID- 1986501
TI  - Prevalence of unsuspected mitral regurgitation and left ventricular diastolic
      dysfunction in patients with coronary artery disease and acute pulmonary edema
      associated with normal or depressed left ventricular systolic function.
AB  - To define the prevalence and role of left ventricular (LV) systolic dysfunction,
      LV diastolic dysfunction and mitral regurgitation (MR) in patients with acute
      pulmonary edema, 40 patients with coronary artery disease and acute pulmonary
      edema were prospectively evaluated within 36 hours of presentation. LV ejection
      fraction and 3 parameters of LV diastolic function were measured with
      radionuclide ventriculography, whereas MR was assessed with Doppler
      echocardiography. LV ejection fraction was normal in 11 (27%) and depressed in 29
      (73%) patients. Moderate or severe MR without LV diastolic dysfunction was common
      and equally prevalent in patients with and without LV systolic dysfunction (33 vs
      38%; difference not significant). Diastolic dysfunction without MR was less
      frequent but equally prevalent in patients with and without systolic dysfunction
      (17 vs 27%; difference not significant). Two (18%) of 11 patients without and 12
      (33%) of 36 patients with LV systolic dysfunction had both MR and LV diastolic
      dysfunction. Furthermore, MR was clinically silent and unsuspected in two-thirds
      of all patients with MR, regardless of a normal or depressed systolic function.
      These data show that there is a high prevalence of unrecognized moderate to
      severe MR in patients with acute pulmonary edema, regardless of the presence or
      absence of LV systolic dysfunction. Furthermore, the prevalence of LV diastolic
      dysfunction without MR is relatively low even in patients with normal LV systolic
      function and pulmonary edema. Thus, unrecognized MR may be an important
      contributor to the syndrome of acute pulmonary edema in patients with normal or
      depressed LV systolic function.

PMID- 1986503
TI  - Exercise thallium-201 imaging in complete left bundle branch block and the
      prevalence of septal perfusion defects.
AB  - To determine the prevalence of septal defects in a generalized referral
      population, the records of 93 consecutive patients with complete left bundle
      branch block (BBB) who underwent symptom-limited treadmill exercise testing with
      thallium-201 myocardial imaging over a 3-year period were reviewed. Segmental
      analysis of the planar thallium-201 images was performed in a blinded fashion
      with agreement by consensus. Computerized quantitative analysis of the images
      also was independently performed, and was correlated with the visual
      interpretations. Forty-seven patients (51%) had normal images, and 46 (49%) had
      defects of greater than or equal to 2 segments. In the abnormal studies, only 13
      patients (14% of the total population) had septal defects, while a much higher
      number of patients, 33 (39%), had inferior or apical defects, or both. Coronary
      angiography was performed in 6 patients with septal defects: Significant
      narrowing of the left anterior descending coronary artery was found in 4
      patients, a narrowed right coronary artery was found in 1, and normal coronary
      arteries were seen in the other patient. In conclusion, whereas previous studies
      have suggested a high percentage of false-positive septal defects in patients
      with left BBB, this study demonstrates a low prevalence (14%) of septal defects
      in a large population of unselected patients presenting for exercise thallium-201
      imaging. Therefore, exercise thallium-201 imaging remains a useful procedure for
      evaluating patients with complete left BBB.

PMID- 1986502
TI  - Ventricular tachycardia and accelerated ventricular rhythm presenting in the
      first month of life.
AB  - Fourteen infants aged less than 1 month presented to our institution during the
      last 22 years with ventricular tachycardia (VT) or accelerated ventricular rhythm
      and a structurally normal heart. In 2, VT was associated with long QT syndrome.
      Both are alive on beta-blocker therapy, 1 with an implanted pacemaker. Twelve
      infants had accelerated ventricular rhythm, and 2 of these died in the first 2
      months of life of unrelated conditions. The other 10 are alive at a median age of
      4 years (range 2 months to 11 years), and none were lost to follow-up.
      Hemodynamic compromise did not occur with accelerated ventricular rhythm. The
      ventricular rate was very close to the sinus rate in all 12, less than 12% above
      the sinus rate. The mean QRS duration during accelerated ventricular rhythm was
      92.5 ms, and averaged twice the QRS duration during sinus rhythm. Fusion beats
      were seen in all 12, and there was atrioventricular dissociation with capture
      beats in 10. In 2, ventriculoatrial conduction was present. Treatment was
      attempted in 5 of the 10 survivors with accelerated ventricular rhythm, and was
      thought to be successful in 4. Treatment was later successfully withdrawn in all
      5, so that all 10 survivors were free of accelerated ventricular rhythm and were
      not receiving antiarrhythmic medications at last follow-up. Because of the
      excellent long-term outcome and the lack of hemodynamic compromise during the
      rhythm, it seems reasonable to withhold antiarrhythmic therapy in infants with
      accelerated ventricular rhythm and await resolution of the rhythm.

PMID- 1986504
TI  - Characterization of spontaneous termination of sustained ventricular tachycardia
      associated with coronary artery disease.
AB  - To characterize the change in cycle length and QRS morphology before spontaneous
      termination of sustained ventricular tachycardia (VT), electrocardiograms were
      recorded and VT cycle length measured for the periods 31 to 21 and 11 to 1 beats
      before termination in 55 episodes from 28 patients with coronary artery disease.
      Beats 31 to 21 were designated as a period of stable arrhythmia and served as a
      reference for changes occurring just before termination. Forty-four episodes of
      VT occurred in the setting of antiarrhythmic drug therapy; 11 episodes occurred
      in patients not treated with antiarrhythmic drugs. Variability in cycle length
      was indexed by the standard deviation of the mean cycle length and by the
      percentage of consecutive cycles varying by greater than or equal to 40 ms (%
      greater than or equal to 40 ms). There was greater variability just before
      termination (standard deviation of the mean cycle length, 25.8 ms; % greater than
      or equal to 40 ms, 16.7%) than during the stable period (standard deviation of
      the mean cycle length, 8.5 ms; % greater than or equal to 40 ms, 5.4%; p less
      than 0.001 for both). This was true irrespective of antiarrhythmic drug use,
      although the differences in the standard deviation of the mean cycle length for
      beats 11 to 1 and for beats 31 to 21 were greater for the antiarrhythmic drug
      group (29.6 vs 8.9 ms, p less than 0.001) than for the group not receiving
      antiarrhythmic drugs (11.0 vs 6.7 ms, difference not significant). No specific
      patterns of cycle length variability characteristic of VT termination were
      found.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1986505
TI  - Duration of the QT interval and total and cardiovascular mortality in healthy
      persons (The Framingham Heart Study experience).
AB  - The baseline electrocardiograms of 5,125 original subjects of the Framingham
      Heart Study were measured to examine the relation of the QT interval corrected
      for heart rate (QTc) to risk of total mortality, sudden cardiac death, and death
      due to coronary artery disease over a 30-year follow-up period. Quintiles of QTc
      (seconds) less than or equal to 0.36, 0.36 to 0.38, 0.39 to 0.40, 0.41 to 0.43
      and greater than or equal to 0.44 were studied in relation to these outcomes.
      There were no significant differences in the risk of total mortality, sudden
      cardiac death or death due to coronary artery disease according to QTc. A similar
      lack of significant association between QTc and these 3 outcomes was observed
      among all persons studied and in the 2 sexes after using a multiple regression
      analysis to control for several potentially confounding characteristics including
      age, gender, cigarette smoking, serum total cholesterol, systolic systemic blood
      pressure and Framingham relative weight. The results of this study fail to
      demonstrate an association between baseline QTc and overall mortality, and deaths
      due to sudden cardiac events or coronary artery disease in a large population
      based cohort of essentially healthy persons in whom pathologic forms of QTc
      prolongation are uncommon.

PMID- 1986506
TI  - Hemodynamic effects of renin inhibition by enalkiren in chronic congestive heart
      failure.
AB  - Previous efforts to block the renin-angiotensin system in patients with chronic
      congestive heart failure (CHF) have focused on 2 distal sites in the system, the
      angiotensin-converting enzyme and the angiotensin II receptor. Recent work,
      however, has led to the development of agents that directly inhibit renin, the
      proximal step in the cascade. In this study, we investigated the hemodynamic
      effects of renin inhibition in 9 patients with chronic CHF by using enalkiren, a
      primate-selective, dipeptide renin inhibitor, which has been previously shown to
      suppress plasma renin activity and to lower blood pressure in hypertensive
      patients. The acute intravenous administration of enalkiren (1.0 mg/kg) produced
      increases in cardiac index (2.0 +/- 0.3 to 2.3 +/- 0.1 liter/min/m2) and stroke
      volume index (26 +/- 3 to 34 +/- 4 ml/m2) and decreases in left ventricular
      filling pressure (31 +/- 3 to 25 +/- 3 mm Hg), mean right atrial pressure (15 +/-
      1 to 13 +/- 2 mm Hg), heart rate (78 +/- 5 to 72 +/- 6 beats/min) and systemic
      vascular resistance (2,199 +/- 594 to 1,339 +/- 230 dynes.s.cm-5) (all p less
      than 0.01 to 0.05). These observations indicate that renin inhibition produces
      hemodynamic benefits in patients with chronic CHF and could potentially provide a
      novel approach to interfering with the renin-angiotensin system in patients with
      this disorder.

PMID- 1986507
TI  - Outcomes of direct coronary angioplasty for acute myocardial infarction in
      candidates and non-candidates for thrombolytic therapy.
AB  - Coronary angioplasty without prior thrombolytic therapy was performed in 383
      patients with acute myocardial infarction (AMI). Patients were divided into 2
      groups depending on whether they were candidates or non-candidates for
      thrombolytic therapy. Patients were not considered thrombolytic candidates if
      they: (1) presented in cardiogenic shock, (2) were greater than or equal to 75
      years of age, (3) had had coronary artery bypass surgery or, (4) had a
      reperfusion time of greater than 6 hours. Thrombolytic and nonthrombolytic
      candidates had similar rates of reperfusion (92 vs 88%), nonfatal reinfarction
      (6.0 vs 5.9%) and recurrent myocardial ischemia (1.8 vs 0%). Thrombolytic
      candidates had a lower mortality rate (3.9 vs 24%, p less than 0.0001) and a
      lower incidence of bleeding (4.6 vs 10.9%, p less than 0.05). Improvement in left
      ventricular ejection fraction at follow-up angiography was 4.4% in thrombolytic
      and 10.5% in nonthrombolytic candidates (p less than 0.002). Ejection fraction
      improved most in patients with anterior wall AMI (7.7% in thrombolytic
      candidates, 15.1% in nonthrombolytic candidates) and in patients with reperfusion
      times greater than 6 hours (14.2%). These outcomes suggest that direct coronary
      angioplasty is a viable alternative method of reperfusion in patients with AMI
      who are candidates for thrombolytic therapy. Nonthrombolytic candidates are a
      high-risk group of patients. Direct coronary angioplasty may be beneficial in
      certain subgroups, especially for patients in cardiogenic shock and for patients
      presenting greater than 6 hours after the onset of chest pain with evidence of
      ongoing ischemia.

PMID- 1986508
TI  - Blood rheology after cardiac valve replacement with mechanical prostheses or
      bioprostheses.
AB  - Arterial thromboembolism is a serious complication in patients after heart valve
      replacement. Abnormalities in blood rheology may contribute to this complication.
      Therefore, the aim of this study was to compare various determinants of blood
      rheology in patients with substitute heart valves with those in healthy controls;
      furthermore, differences between patients with mechanical valves and those with
      bioprostheses should be investigated. The hemorrheologic determinants-
      fibrinogen, plasma viscosity, red cell aggregation, hematocrit and platelet
      aggregation--were studied in 92 patients with mechanical bileaflet valves, in 28
      patients with bioprostheses and in 29 control subjects; the time since valve
      replacement was greater than or equal to 9 months. Fibrinogen, plasma viscosity,
      red cell and spontaneous platelet aggregation were found to be increased in all
      patients after heart valve replacement compared with normal subjects (fibrinogen:
      348 +/- 87 vs 267 +/- 66 mg/dl, p less than 0.01; plasma viscosity: 1.71 +/- 0.1
      vs 1.66 +/- 0.1 mPas, p less than 0.05; red cell aggregation: 9.9 +/- 2 vs 7.8 +/
      2 U, p less than 0.01; platelet aggregation: 22 +/- 15 vs 13 +/- 13%, p less
      than 0.01); among patients, fibrinogen, plasma viscosity and spontaneous platelet
      aggregation were higher in mechanical valves than in bioprostheses (fibrinogen:
      359 +/- 95 vs 314 +/- 41 mg/dl, p less than 0.01; plasma viscosity: 1.72 +/- 0.1
      vs 1.68 +/- 0.1 mPas, p less than 0.1; platelet aggregation: 23 +/- 15 vs 16 +/-
      11%; p less than 0.05), whereas no difference could be found for red cell
      aggregation (9.7 +/- 2 vs 10.5 +/- 2%, p greater than 0.05).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1986509
TI  - Hemodynamic effects of ketamine, hypoxia and hyperoxia in children with
      surgically treated congenital heart disease residing greater than or equal to
      1,200 meters above sea level.
AB  - Little data are available on the hemodynamic effects of premedications and
      anesthetic agents on infants and children. Ketamine is the most frequently used
      anesthetic agent for cardiac catheterization procedures in pediatric patients
      with congenital heart disease. Previous reports both suggest and deny ketamine's
      pulmonary vasoreactive effects. Since the advent of sophisticated noninvasive
      equipment, one of the few indications for cardiac catheterization is to obtain
      accurate pressure data. If ketamine alters pulmonary vascular resistance, it
      would negate the primary reason for the procedure. Because the patient population
      studied herein resides greater than or equal to 1,200 meters above sea level,
      concerns about pharmacologic effects on pulmonary vascular resistance are
      enhanced. Simultaneous pulmonary artery and aortic pressures, thermodilution
      cardiac outputs, and blood gases were measured in room air (16% oxygen) and with
      ketamine infusion in 14 patients at cardiac catheterization. Reaction to hypoxia
      identified 3 groups: normal, intermediate and hyperresponders. The normal
      responders had normal resistance ratios (0.11) in room air and had little
      resistance ratio response to hypoxia (+0.02), hyperoxia (-0.03) or ketamine
      (+0.01). The intermediate responders had a slightly higher but normal resistance
      ratio (0.20) in room air, and a moderate reaction to hypoxia (+0.13), hyperoxia (
      0.08) and ketamine (+0.11). The hyperresponders had an elevated resistance ratio
      (0.42) in room air and a striking reaction to hypoxia (+0.65), hyperoxia (-0.17)
      and ketamine (+0.49). Hypoxia and ketamine have a greater effect on resistance
      ratio than hypoxia alone in patients with reactive pulmonary vascular beds.
      Ketamine should not be used in children undergoing procedures to establish
      operability based on pulmonary vascular resistance or pulmonary vascular
      reactivity.

PMID- 1986510
TI  - Comparison of exercise stress testing with ambulatory electrocardiographic
      monitoring in the detection of myocardial ischemia after unstable angina
      pectoris.

PMID- 1986511
TI  - Circadian variation in pain onset in unstable angina pectoris.

PMID- 1986512
TI  - Decrease of right and left atrial sizes after direct-current electrical
      cardioversion in chronic atrial fibrillation.

PMID- 1986513
TI  - Cardiac rhythm precipitating automatic implantable cardioverter-defibrillator
      discharge in outpatients as detected from transtelephonic electrocardiographic
      recordings.

PMID- 1986514
TI  - Captopril versus captopril plus hydrochlorothiazide for essential hypertension in
      Koreans.

PMID- 1986515
TI  - Velocity gradients across normal cardiac valves.

PMID- 1986516
TI  - The premaxillary-maxillary suture and orthodontic mechanotherapy.
AB  - Even though there has been debate over whether a separate premaxilla exists in
      the human being, it has been suggested that the premaxillary-maxillary suture
      remains patent into adolescence and provides an explanation for the action of
      certain orthodontic and orthopedic appliances. To assess whether this suture is
      pertinent to an understanding of appliance effects, the skulls of 50 subadult
      subjects were scrutinized to determine patency with regard to age. Remnants of a
      premaxillary-maxillary suture may be present on the surface of the palate at all
      ages studied, and often this suture extends deep to the surface. However, in no
      case was the suture continuous so as to distinguish a distinct premaxilla. These
      findings disprove the claim that the premaxillary-maxillary suture system
      provides an explanation for any form of orthodontic or orthopedic therapy.

PMID- 1986517
TI  - Comparison between electric toothbrushing and manual toothbrushing, with and
      without oral irrigation, for oral hygiene of orthodontic patients.
AB  - This study evaluated the effectiveness of one electric toothbrush and oral
      irrigation system in comparison with manual toothbrushing in 20 orthodontic
      patients. Twenty patients performed four oral hygiene routines for at least 4
      weeks each. The routines included manual toothbrushing alone, electric
      toothbrushing alone, manual toothbrushing plus irrigation, and electric
      toothbrushing plus irrigation. Baseline plaque and gingival scores were recorded,
      and both indices were again recorded after each routine. The index used to
      evaluate gingival health was a slight modification of the Silness and Loe
      gingival index, while the plaque index was similar to the patient hygiene
      performance (PHP) index developed by Podshadley and Haley. The average overall
      scores for plaque and gingival condition for all patients who used each of the
      four oral hygiene routines were compared with a repeated-measures, analysis-of
      variance statistical evaluation. The values obtained from the analysis showed
      that there were no significant differences between the means for plaque and
      gingival health in each group. The probabilities that these conclusions are
      incorrect are 18% for plaque and 2% for gingival health. Testing for validity of
      the data was done by more than one researcher, with consistent results.

PMID- 1986518
TI  - An analysis of the effect of tooth intrusion on the microvascular bed and
      fenestrae in the apical periodontal ligament of the rat molar.
AB  - An analysis of the rat apical periodontal ligament (PDL) microvascular bed and
      fenestrae was conducted to evaluate the effect of a continuous 1.0 N intrusive
      tooth load for 30 minutes. The microvascular bed consisted of postcapillary-sized
      venules, venous and arterial capillaries, and terminal arterioles. Intrusion
      produced significant increases (p less than 0.01) in vascular volume for
      postcapillary-sized venules and venous capillaries in three of the four animals.
      Arterial capillaries, overall, showed a statistically significant increase (p
      less than 0.01). The endothelial surface area (micron2 x 10(6)) per cubic
      millimeter of PDL responded variably in postcapillary-sized venules and venous
      capillaries but showed a strong trend to increase in arterial capillaries. After
      tooth intrusion a significant reduction (p less than 0.01) occurred in the number
      of fenestrae per square micrometer of endothelium in postcapillary-sized venules
      and venous capillaries. Fenestrae in the control PDL had a mean diameter of 51.5
      nm +/- 0.6 (SE), whereas those on the intrusion side were smaller (p less than
      0.05), measuring 49.9 nm +/- 0.4 (SE).

PMID- 1986519
TI  - Neurotoxic causation of paresthesia.

PMID- 1986520
TI  - Recommendation for postretention study.

PMID- 1986522
TI  - Ceramic brackets tested in study no longer in circulation.

PMID- 1986521
TI  - Orthodontics and TMJ disorders.

PMID- 1986523
TI  - Iatrogenic pulpal reactions to orthodontic extrusion.
AB  - A careful review of the literature reveals an absence of studies about the
      reactions of dental pulp to orthodontic extrusion. The purpose of the present
      research investigation is to study the pulpal reactions and the sequence of
      histologic events in human dental pulp after orthodontic extrusion. The sample
      consisted of 36 intact maxillary first premolars of young adult orthodontic
      subjects. The mean age of the subjects was 18 years. Eighteen maxillary first
      premolars were extruded, under controlled conditions with the aid of fixed
      edgewise orthodontic appliances, for either 1, 2, or 4 weeks. The contralateral
      maxillary first premolars were not extruded and were used as controls.
      Immediately after removal of the appliances, all the maxillary first premolars
      were extracted. The pulps were histologically examined in a double-blind
      experiment. The results obtained from this study indicate that certain
      characteristic pulpal reactions arise from orthodontic extrusion. These reactions
      involve circulatory disturbances with congested and dilated blood vessels,
      odontoblastic degeneration, vacuolization and edema of the pulp tissues, and (by
      the fourth week) manifestation of fibrotic changes. It is speculated that the
      vacuolization of the pulp tissues (which occurred after the application of
      extrusive orthodontic forces in young adult subjects) resulted from a prolapse of
      the pulp, made possible by the relatively wide apical foramina. However, the
      odontoblastic degeneration is most probably the result of a compromised blood
      supply. The authors believe that this study constitutes a building block for
      establishing a more complete biologic foundation for orthodontic tooth movement.
      Further studies are suggested to reach more definitive conclusions.

PMID- 1986524
TI  - Patient characteristics and treatment variables associated with apical root
      resorption during orthodontic treatment.
AB  - Multivariate analysis of patient characteristics and clinical variables was
      carried out with the maximum single maxillary incisor apical root resorption for
      each patient as the dependent variable. Root lengths were measured in
      standardized intraoral radiographs from 485 consecutively treated patients, 11.5
      to 25 years of age. The correlation matrix revealed a complex pattern of positive
      and negative associations between the six pretreatment and seven treatment
      variables. Variables found to contribute significantly to apical root resorption
      were overjet, history of trauma to maxillary incisors before initiation of
      treatment, time of treatment with rectangular arch wires, time of treatment with
      Class II elastics, lip/tongue dysfunction, and/or history of finger-sucking
      habits persisting beyond the age of 7 years, and impacted maxillary canines to be
      corrected orthodontically. Clinical application of an open activator was
      significantly correlated with overjet but negatively correlated with apical root
      resorption, with the use of rectangular arch wires and/or Class II elastics, and
      with total banding time.

PMID- 1986525
TI  - A morphometric study of bone surfaces and skin reactions after stimulation with
      static magnetic fields in rats.
AB  - The present investigation was undertaken to measure any bone surface changes
      after stimulation with orthodontic magnets and, furthermore, to examine the soft
      tissue in immediate contact with the magnets. Both distal parts of the tibial
      hind legs in six groups of young rats were fitted with devices holding two
      orthodontic magnets in the experimental legs and similar devices without magnets
      in the control legs. The animals were killed after 2, 3, and 4 weeks.
      Morphometric evaluation showed significant increases in resorbing areas after 3
      and 4 weeks. Similarly, a reduction was evident in the number of epithelial cells
      under the areas where the magnets had been applied. These findings indicate that
      the stimulation of bone resorption in the present study may have been caused by
      inhibition of the bone-lining osteoblasts. This proposition is supported by the
      apparent inhibitory effect of the magnetic fields on epithelial recycling that
      was seen as a reduced thickness of the epithelium under the magnets.
      Consequently, static magnetic fields should be used with care in orthodontic
      practice until a more complete understanding of their mechanism of action has
      been established.

PMID- 1986526
TI  - Quantitative description of the shape of the mandible.
AB  - The purpose of this study was to provide quantitative data on the shape of the
      mandible at the period around the pubertal growth spurt and to test the
      hypothesis that early mandibular shape may influence the amount and direction of
      subsequent mandibular growth. Longitudinal data from lateral cephalograms of 55
      white female and 39 white male subjects were used. The mandibular outline from
      articulare to gnathion was analyzed into cosine curves, according to the Fourier
      equation. The resulting Fourier coefficients, representing mandibular outline
      shape, were analyzed statistically in relation to age, sex, craniofacial pattern,
      and mandibular growth rotation. Statistically significant growth changes of the
      Fourier coefficients were observed, especially during the postpubertal period,
      indicating a decrease in the gonial angle with age. Sex-related differences in
      shape were observed at all ages, male subjects showing a more rounded shape of
      the mandible than female subjects. Mandibular shape, as represented by the
      Fourier coefficients, was correlated to cephalometric variables, indicating
      mandibular inclination, but only poorly to cephalometric variables, indicating
      anteroposterior jaw relation. Total rotation of the mandible during growth could
      not be predicted by mandibular shape.

PMID- 1986527
TI  - Comparison of convection heat sterilization units for the orthodontic office.
AB  - Convection heat has become a popular means of sterilization for orthodontic
      practices. Several commercial brands are currently being marketed. This
      investigation compares the Cox sterilizer, the Dentronix DDS 5000, and a
      Farberware convection oven by means of thermal and bacteriologic testing. Thermal
      testing was conducted with a thermocouple in well-defined areas of each oven,
      while bacterologic evaluation involved Bacillus subtilis spore strips placed in
      specific sectors. The results showed that specific areas of the Cox sterilizer
      dropped below 375 degrees F during the sterilization cycle, while the DDS 5000
      maintained temperatures above 375 degrees F. The Farberware oven reached a mean
      temperature (including 1 standard deviation) above 375 degrees F when set at 400
      degrees F after the oven was allowed to warm up for 13 minutes. Spore growth was
      detected in several sectors of both the Cox sterilizer and the DDS 5000. No
      growth was seen in the Farberware oven.

PMID- 1986528
TI  - Crozat appliance therapy for an arch-length discrepancy problem.
AB  - The case involved a white male subject, aged 10 years 6 months, with a Class I
      molar relationship complicated by a deep overbite and impaction of all four
      permanent canines, which were completely blocked out of the arches. The growth
      rate of the arches was found to be abnormal, and there was premature loss of the
      deciduous teeth. Over a period of approximately 5 years, with intermittent pauses
      to allow growth to catch up with treatment, the Crozat removable appliance was
      used to help establish the arch form and correct the plane of occlusion.

PMID- 1986529
TI  - The effectiveness of a counterrotational-action power toothbrush on plaque
      control in orthodontic patients.
AB  - This study compared counterrotational-action power toothbrushing with manual
      toothbrushing in effectiveness on plaque control and gingival health in 20
      randomly selected orthodontic patients at the University of Missouri-Kansas City.
      A blind two-group crossover design was used. Gingival and plaque scores were
      recorded, and a prophylaxis was given to bring the plaque score to zero. Ten
      subjects received counterrotational power brushes, and ten subjects received
      manual brushes. Instructions appropriate to each brushing method were given by a
      hygienist. At 30 and 60 days, plaque and gingival scores were recorded and a
      prophylaxis was given. At 60 days the subjects who were using power brushes were
      switched to manual brushes, and the subjects who were using manual brushes were
      switched to power brushes. At 30 and 60 days, plaque and gingival scores were
      recorded and a prophylaxis was given. Plaque and gingival scores were
      significantly less (p less than 0.01) after brushing 2 months with the
      counterrotational power brush than with the manual brush. This finding was
      irrespective of the sequence in which the brushes were used.

PMID- 1986530
TI  - Nonextraction treatment of severe Class II, division 2 malocclusions. Part 2.
AB  - Nonextraction treatment of a severe Class II, Division 2 malocclusion is
      presented. Timing, sequencing of appliance therapy, and segmental arch treatment
      are discussed. The effects of orthodontic treatment, pubertal growth, and
      postpubertal growth are illustrated with different growth responses. Correction
      of the handicapping malocclusion was achieved by the development of arch
      circumference, torque, intrusion of incisors, and vertical buccal dentoalveolar
      development. Various subtypes of Class II, Division 2 malocclusion are presented.
      Pretreatment and posttreatment records are evaluated.

PMID- 1986531
TI  - Surgically assisted palatal expansion: an important consideration in adult
      treatment.
AB  - An increasing percentage of orthodontic patients are adults with challenging
      malocclusions. While some aspects of many adult cases are similar to those seen
      in children, others must be addressed quite differently. Although many adults
      appear to be generally more cooperative than children in dealing with the
      inconveniences of orthodontic treatment, they nonetheless require efficient, less
      lengthy treatment plans. Many are intolerant of multiple extractions or elaborate
      surgery. Consequently, the need for practical treatment plans that assure good,
      stable results is real. Also, any perceived change in the soft tissue profile
      (positive or negative) is likely to be significant to the patient. The case
      presented here, in which surgically assisted palatal expansion and extraction of
      one mandibular incisor were employed, illustrates an approach to a difficult
      adult orthodontic problem that is both practical and efficient from diagnostic
      and biomechanical points of view. In this case, in which an adult patient
      exhibited significant transverse discrepancies and dental crowding, a treatment
      plan that addressed these considerations was employed.

PMID- 1986532
TI  - Legal aspects of orthodontic practice: risk management concepts. Alternative
      treatment plans.

PMID- 1986533
TI  - Hepatobiliary manifestations of the acquired immune deficiency syndrome.
AB  - Patients with the acquired immune deficiency syndrome (AIDS) frequently develop
      hepatic dysfunction. Although hepatic injury may indirectly result from
      malnutrition, hypotension, administered medications, sepsis, or other conditions,
      the hepatic injury is frequently due to opportunistic hepatic infection, directly
      related to AIDS. Infection with Mycobacterium avium intracellulare typically
      occurs in patients with advanced immunocompromise and with systemic symptoms due
      to widely disseminated infection. In contrast, hepatic tuberculosis often occurs
      with less advanced immunocompromise. Cytomegaloviral infection may produce a
      hepatitis. Cytomegaloviral and cryptosporidial infections have been implicated as
      causes of acalculous cholecystitis and of a secondary sclerosing cholangitis.
      About 10-20% of patients with AIDS have chronic hepatitis B infection. These
      patients tend to develop minimal hepatic inflammation and necrosis. The clinical
      findings in patients with hepatic cryptococcal infection are usually due to
      concomitant extrahepatic infection. Hepatic histoplasmosis usually develops as
      part of a widely disseminated infection with systemic symptoms. Hepatic
      involvement by Kaposi's sarcoma is rarely documented ante mortem because an
      unguided liver biopsy is an insensitive diagnostic procedure. Patients with non
      Hodgkin's lymphoma of the liver typically have lymphadenopathy, hepatomegaly, and
      systemic symptoms. As a pragmatic approach, patients with liver dysfunction and
      HIV-related disease should have a sonographic or computerized tomographic
      examination of the liver. Patients with dilated bile ducts should undergo
      endoscopic retrograde cholangiopancreatography because opportunistic infection
      may produce biliary obstruction. Patients with a focal hepatic lesion should be
      considered for a guided liver biopsy. Patients with a significantly elevated
      serum alkaline phosphatase level should be considered for a percutaneous liver
      biopsy. When performed for these indications, liver biopsy will demonstrate a
      significant disease involving the liver in about 50% of patients with AIDS and in
      about 25% of patients who are HIV seropositive but who are not known to have
      AIDS. The clinical impact of a diagnostic biopsy is blunted by a lack of
      efficacious therapy for many opportunistic infections.

PMID- 1986534
TI  - Colonoscopic fine needle aspiration cytology in the diagnosis of ileocecal
      tuberculosis.
AB  - Two cases of ileocecal tuberculosis are presented. The diagnosis was achieved by
      endoscopic fine needle aspiration cytology (FNAC), while endoscopic biopsies and
      brush cytology were negative. The usefulness of endoscopic FNAC in the diagnosis
      of gastrointestinal tract tuberculosis is highlighted.

PMID- 1986536
TI  - A colonic stress test--is it of value?

PMID- 1986535
TI  - Bleeding ectatic vascular lesion involving the sigmoid colon, endoscopically
      indistinguishable from angiodysplasia, in an 8-yr-old boy.
AB  - An 8-yr-old Japanese boy was hospitalized, complaining of active hematochezia. He
      was shown to have a cherry-red, blood-oozing area of vascular dilation with
      mucosal prominence in the sigmoid colon by endoscopy, but had no other
      mucocutaneous vascular abnormalities. A family history was noncontributory. Under
      the clinical diagnosis of angiodysplasia of the sigmoid colon, he underwent an
      elliptical resection of the part, based on the intraoperative endoscopic
      findings. However, histological examination of the surgical specimen revealed a
      totally different picture from that seen in angiodysplasia: the thin-walled,
      markedly ectatic, nontortuous veins with hemorrhage were seen only just below the
      muscularis mucosae, around which the normal ones were shown to coexist. He has
      had no rebleeding for the past 3 yr. This lesion is considered to be an isolated
      congenital visceral telangiectasia involving veins.

PMID- 1986537
TI  - At bat with paracentesis: home runs or singles?

PMID- 1986538
TI  - The etiology of esophageal cancer: searching for clues.

PMID- 1986540
TI  - Cholecystokinin, gallbladder function, and diabetes mellitus.

PMID- 1986539
TI  - Upper esophageal webs, iron deficiency anemia, and esophageal cancer.

PMID- 1986541
TI  - Intraoperative hemorrhage affects endothelin-1 concentrations.

PMID- 1986542
TI  - Recurrent colonic histoplasmosis after standard therapy with amphotericin B in a
      patient with Job's syndrome.

PMID- 1986543
TI  - Essential mixed cryoglobulinemia as a cause of gastrointestinal hemorrhage.

PMID- 1986545
TI  - Is continuous, esophageal pH monitoring reliable in a community practice setting?

PMID- 1986544
TI  - Triple therapy for Helicobacter pylori in nonulcer dyspepsia.

PMID- 1986546
TI  - Changes in thrombin-antithrombin III complex after endoscopic injection
      sclerotherapy.

PMID- 1986547
TI  - Omeprazole may kill Helicobacter pylori.

PMID- 1986548
TI  - The use of bismuth in gastroenterology. The ACG Committee on FDA-Related Matters.
      American College of Gastroenterology.

PMID- 1986549
TI  - Controversies, dilemmas, and dialogues. Is there an effective nonsurgical
      treatment for pain in chronic pancreatitis?

PMID- 1986550
TI  - Corticosteroids as therapeutic agents in liver diseases.

PMID- 1986551
TI  - Upper gastrointestinal bleeding in dengue fever.
AB  - Twenty-six virologically and serologically confirmed Dengue patients with signs
      of upper gastrointestinal tract bleeding (13.1%) were studied during the 1987
      outbreak in southern Taiwan. Within a 1-yr period from 1987 to 1988 in Kaohsiung
      Chang Gung Memorial Hospital, there were 198 patients with Dengue fever
      confirmed. Viral isolation and serological studies indicated that type I Dengue
      was the cause. There was no evidence of sequential secondary infection among
      them. The 26 patients were evaluated gastroduodenoscopically. Most of the Dengue
      patients who developed upper gastrointestinal bleeding had gastric ulcers or
      duodenal ulcers; superficial and hemorrhagic gastritis are the other relevant
      endoscopic findings. Thirteen patients (50%) had a past history of peptic ulcer
      symptoms, whereas the other 13 did not. Dengue infection is a precipitating
      factor in inducing peptic ulcer bleeding because of hemostatic derangements.
      Supportive therapy and blood transfusions alone were adequate treatment, except
      for one patient who required surgery due to massive bleeding of a duodenal ulcer.
      No mortality was observed in this study.

PMID- 1986552
TI  - Sequential esophageal motility studies after endoscopic injection sclerotherapy:
      a prospective investigation.
AB  - To assess prospectively the effects of endoscopic intravariceal sclerosis (EIS)
      on esophageal function, we performed esophageal manometry on 13 cirrhotic
      patients before EIS, 24 h after the second session and 4 wk after the fourth
      session. EIS had no impact on lower esophageal sphincter pressure. However, a
      significant decrease in the amplitude of peristaltic waves was observed
      immediately post-EIS in the lower two-thirds of the esophagus. There was no
      modification of duration or velocity of progression of peristaltic waves. A four
      fold increase in simultaneous contractions was observed early after EIS. These
      changes were reversible, as assessed by late esophageal testing after EIS. No
      correlations were demonstrated between esophageal motor parameters and doses of
      sclerosant. We conclude that sclerosant injection into the esophageal wall
      acutely impairs esophageal motility, but motor function is partially restored 4
      wk after completion of EIS, suggesting that dysmotility is reversible.

PMID- 1986553
TI  - Pharmacokinetics of famotidine after intravenous administration in liver disease.
AB  - The pharmacokinetics of famotidine were studied after the administration of a
      single intravenous dose of 20-mg to seven normal volunteers, six patients with
      chronic hepatitis, 14 patients with compensated cirrhosis, and seven patients
      with decompensated cirrhosis. The plasma terminal elimination half-life of
      famotidine was significantly prolonged and famotidine total body clearance was
      significantly reduced in patients with decompensated cirrhosis, whose creatinine
      clearance was 57.2 +/- 6.7 ml/min/1.48 m2, but these changes were not significant
      in patients with chronic hepatitis (creatinine clearance: 109.2 +/- 10.5
      ml/min/1.48 m2) or in patients with compensated cirrhosis (creatinine clearance:
      72.2 +/- 26.5 ml/min/1.48 m2 in comparison with normal volunteers. The total
      volume of distribution at steady state was not significantly different between
      the normal volunteers and the three groups of patients. Famotidine total body
      clearance showed a weak but significant correlation with the creatinine clearance
      (r = 0.66, p less than 0.001), serum albumin level (r = 0.51, p less than 0.01),
      and serum total bilirubin level (r = 0.36, p less than 0.05), which suggested
      that the reduction in clearance was due in part to the concomitant renal
      impairment, as well as hepatic dysfunction in these patients. In conclusion,
      famotidine total body clearance was reduced in decompensated cirrhosis,
      indicating that the dose schedule requires modification in patients with this
      condition.

PMID- 1986555
TI  - Short-term course of corticosteroids in the treatment of resistant ascites
      complicating schistosomal liver disease.
AB  - The aim of this work was to evaluate the effect of short-term corticosteroids in
      resistant ascites complicating schistosomal liver disease after 4 wk or more on
      standard treatment. Thirty-seven patients were randomly allocated to two groups:
      Group I (18 patients) was put on 40 mg furosemide and 200 mg spironolactone, in
      addition to a 15-day, tapering dose of prednisone (15, 10, 5 mg). Group II (19)
      patients received the same diuretics without steroids, and served as controls. At
      the end of a 2-wk course of therapy, the mean variations were as follows: body
      weight in patients in Group I ("cases") decreased by 9.8 kg, compared with 4.3 kg
      in controls; abdominal girth decreased by 7.4 cm in cases, compared with 3.6 cm
      in controls; urine output increased by 635.9 ml in cases, compared with 364.6 ml
      in controls; urinary sodium excretion increased by 16.5 mEq/day in cases,
      compared with 4.1 mEq/day in controls. These differences between cases and
      controls were found to be statistically significant (p less than 0.01). On the
      other hand, there were insignificant differences as regards decrease in blood
      urea (3.2 g/dl for cases and 2.7 g/dl for controls), decrease in serum creatinine
      (0.2 mg/dl for both cases and controls), increase in serum albumin (0.3 g/dl in
      cases and 0.2 g/dl in controls), increase in serum sodium (3.2 mEq/L in cases and
      2.7 mEq/L in controls), and increase in serum potassium (0.2 mEq/L in cases and
      0.4 mEq/L in controls). We conclude that a short-term course of corticosteroids
      in conjunction with standard diuretics has proved to be an effective, safe, and
      economical modality to relieve resistant hepatic ascites. It can be considered a
      temporary alternative to paracentesis with albumin infusion.

PMID- 1986554
TI  - Reduction in hepatic venous pressure gradient as a consequence of volume
      contraction due to chronic administration of spironolactone in patients with
      cirrhosis and no ascites.
AB  - The effect of plasma volume contraction induced by a 4-wk administration of
      spironolactone or furosemide on the hepatic venous pressure gradient was
      evaluated in consecutively allocated patients with cirrhosis and no ascites. In
      the spironolactone group (n = 15), the hepatic venous pressure gradient decreased
      significantly (p less than 0.005), by 21.8%, with a significant contraction of
      circulating plasma volume (p less than 0.01). Although there were no
      statistically significant correlations between the change in hepatic venous
      pressure gradient and changes in circulating plasma volume or in simultaneously
      determined systemic hemodynamics, a significant negative correlation (r = -0.74,
      p less than 0.01, n = 12) between the hepatic venous pressure gradient change and
      the post-treatment plasma aldosterone levels was found. However, in the
      furosemide group (n = 10), the hepatic venous pressure gradient and circulating
      plasma volume did not significantly decrease. Our data demonstrated a significant
      reduction in the hepatic venous pressure gradient on a chronic administration of
      spironolactone, which may have been due to volume contractions in patients with
      cirrhosis and no ascites.

PMID- 1986556
TI  - The combination of prednisone and colchicine in patients with primary sclerosing
      cholangitis.
AB  - Primary sclerosing cholangitis is a cholestatic liver disease characterized by
      inflammation and fibrosis of the biliary tract. The cause of the disease is
      unknown, and no effective medical treatment exists. In this study, 12 patients
      received a combination of low-dose prednisone (10 mg/day) and colchicine (0.6 mg
      bid). Their course was compared with that of a group of concurrent historical
      controls. At 6 and 12 months, there was significantly more improvement in liver
      test results over baseline values in patients receiving prednisone and colchicine
      than in the untreated controls. At 24 months, however, no significant differences
      in biochemical tests were appreciated between treated and untreated patients.
      Analysis of serial liver biopsies showed no differences in histologic change in
      the two groups. During the 2 yr of follow-up, there were two deaths in the
      control group but none in the treated group. Four untreated patients developed
      ascites; gastrointestinal bleeding developed in three untreated patients, one of
      whom developed ascites. In contrast, in the treated group, ascites and bleeding
      developed in only one patient. We conclude that the combination of colchicine and
      prednisone does not retard histologic progression or progression of standard
      liver tests after 2 yr of therapy. There is a trend toward less clinical
      deterioration and improved survival after 2 yr of treatment. On the basis of
      these findings, we would not advocate empiric use of these drugs for patients
      with primary sclerosing cholangitis, but suggest that, if they are to be used at
      all in PSC, they be evaluated in a controlled clinical trial as treatment for
      this as yet incurable disease.

PMID- 1986557
TI  - Modified Kraske approach for disease of the mid-rectum.
AB  - A modification of Dr. Paul Kraske's approach for removal of mid-rectal lesions
      has been used in 11 patients from 1977 to 1988 by the senior authors. Patients
      ranged in age from 56 to 89 yr, with an average of 67 yr. There were seven male
      and four female patients. Indications for surgery were as follows: villous
      adenoma (seven), carcinoid (one), recurrent dysplasia in a previous endoscopic
      polypectomy site (one), positive distal margin for neoplasm following low
      anterior sigmoid resection (one), and adenocarcinoma in one elderly poor-risk
      patient. All lesions were in the middle rectum (7-11 cm from the anal verge,
      average 9 cm). The postoperative stay ranged from 6 to 12 days with a mean of 8
      days. The average follow-up for the 11 patients is 3 1/2 yr (1 month to 7 yr),
      with only one patient having a local recurrent lesion. There was no morbidity or
      mortality. We conclude that this modification of the Kraske approach offers a
      good alternative for excision of mid-rectal lesions in terms of technical ease,
      efficacy, safety, and patient tolerance. The modified Kraske approach is
      indicated in certain situations and should be a part of the surgeon's
      armamentarium.

PMID- 1986558
TI  - Disseminated Pneumocystis carinii infection with hepatic involvement in a patient
      with the acquired immune deficiency syndrome.
AB  - Extrapulmonary infection with Pneumocystis carinii (P. carinii) in AIDS patients
      is uncommon, and is often described only at postmortem examination. Although most
      antemortem cases involve spread to the bone marrow or spleen, P. carinii
      involvement of other organs has only recently been described. Despite the
      frequency of liver enzyme abnormalities in AIDS patients with a history of P.
      carinii pneumonia, P. carinii has been observed only rarely in the liver. We
      present a well-documented case of P. carinii involving the liver in an AIDS
      patient with P. carinii pneumonia and progressive liver enzyme abnormalities. We
      suggest that P. carinii infection should be considered in the differential
      diagnosis of AIDS-related liver disease.

PMID- 1986559
TI  - Nodular regenerative hyperplasia: a cause of ascites and hepatomegaly after
      chemotherapy for leukemia.
AB  - Tender hepatomegaly and ascites occurred in a young woman receiving cytosine
      arabinoside and daunorubicin for acute myelogenous leukemia. Whereas veno
      occlusive disease was suspected clinically, liver biopsy showed nodular
      regenerative hyperplasia with no evidence of hepatic vein abnormalities. It is
      postulated that nodular regenerative hyperplasia can be initiated by
      hepatotoxicity of chemotherapy agents used to treat leukemia and/or that these
      agents exacerbate clinical manifestations of this histological abnormality.
      Nodular regenerative hyperplasia should be added to the list of liver problems
      occurring in patients with leukemia.

PMID- 1986560
TI  - Eosinophilic ascites due to hyperinfection with Strongyloides stercoralis.
AB  - We report the case of a patient with cryptogenic cirrhosis, new onset ascites,
      and hyperinfection with Strongyloides stercoralis who had significant
      eosinophilia of the peritoneal fluid. The eosinophilia resolved with treatment of
      the S. stercoralis infection, and did not recur during two subsequent episodes of
      ascites and spontaneous bacterial peritonitis. Eosinophilic ascites is rare in
      parasitic infection, but it has been described in a variety of disorders which
      are discussed.

PMID- 1986561
TI  - Chylous ascites due to sarcoidosis.
AB  - A 33-yr-old black female with systemic sarcoidosis developed chylous ascites. A
      CT scan showed extensive mesenteric lymphadenopathy. At laparotomy, the
      mesenteric and para-aortic lymph nodes were enlarged and diffusely matted.
      Histologically, normal lymph node morphology was virtually replaced with
      noncaseating granulomas. Corticosteroids and dietary manipulations were
      unsuccessful in managing the ascites, and repeated large-volume paracentesis was
      necessary to provide symptomatic treatment. This is the first reported case of
      chylous ascites caused by sarcoidosis.

PMID- 1986562
TI  - Enteroliths causing intermittent obstruction in a patient with Crohn's disease.
AB  - Calcified enteroliths as a cause of intermittent small bowel obstruction is an
      uncommon clinical entity. The pathophysiological mechanism involves stasis of
      intestinal contents and has been associated with Meckel's diverticulum,
      tuberculosis, and regional enteritis. This case describes prophylactic operative
      intervention in a symptomatic patient with enteroliths as a result of Crohn's
      disease.

PMID- 1986563
TI  - Endoscopic placement of a Foley catheter across a stricture and rectovaginal
      fistula to perform a barium enema.
AB  - Evaluation of enteric fistulas is often best performed with barium contrast
      studies. Clinical situations that preclude the satisfactory installation of
      barium decrease the yield of the study. A case is presented of a 59-yr-old female
      with stage III-B cervical carcinoma and a known rectovaginal fistula with an
      adjacent sigmoid colon stricture. An additional more proximal, enteric fistula
      was suspected. Definitive preoperative knowledge of the existence or absence of
      this fistula would have shortened the duration of a planned palliative
      intervention. The rectovaginal fistula and stricture precluded adequate barium
      and air installation for contrast study. Colonoscopy was unsuccessful. We have
      developed a combined technique in which the endoscopic placement of a semirigid
      guidewire allowed placement of a Foley catheter across the fistula and stricture.
      Successful barium study was performed. Intraoperative time and hospital stay were
      shortened.

PMID- 1986565
TI  - Preservation of renal reserve in chronic renal disease.
AB  - Protein-induced increases in glomerular filtration rate (GFR), termed renal
      reserve, is said to be abrogated with the onset of renal disease. However, this
      notion is inconsistent with the results from animal studies which suggest that
      alterations in protein intake modulate the glomerular hemodynamics in
      experimental renal disease. Accordingly, 12 normal subjects and 15 patients with
      renal disease received a protein meal providing 1 g/kg body weight protein. The
      subjects were pretreated with either placebo or an angiotensin I converting
      enzyme inhibitor, enalapril. A significant (P less than 0.05) increase in inulin
      and para-aminohippurate (PAH) clearance was noted in normal subjects as well as
      in patients with renal disease. The increase in GFR over basal values in normal
      subjects (28 +/- 9%), patients with moderate renal failure (20 +/- 13%), and
      advanced renal failure (21 +/- 14%) was not different. Plasma renin activity was
      unchanged following protein meal in the placebo studies although it increased
      following enalapril administration. Enalapril pretreatment did not alter the
      glomerular vasodilation and hyperfiltration following protein meal. We conclude
      that protein meal induces glomerular hyperfiltration in renal disease and that
      this protein-induced hyperfiltration is not mediated by angiotensin II. Because
      glomerular hyperfiltration is implicated in the progression of renal disease,
      these data suggest that even in patients who have advanced renal failure, high
      protein diets may exert a detrimental effect on the kidney.

PMID- 1986564
TI  - The effect of angiotensin-converting enzyme inhibition and dietary protein
      restriction in the treatment of proteinuria.
AB  - Both angiotensin-converting enzyme inhibitors and dietary protein restriction
      have been reported to reduce urinary protein losses in patients with chronic
      glomerular diseases. We evaluated these two therapies in 12 such patients
      ingesting a constant metabolic diet containing 1.6 g protein/kg body weight per
      day. After a steady-state was achieved during a 3-week baseline period, patients
      were randomly assigned to either enalapril, titrated to reduce mean arterial
      pressure by 10 mm Hg, or an isocaloric 0.8 g/kg protein diet. Five patients in
      each group completed 3 additional weeks of observation during the treatment
      period. Enalapril resulted in an average reduction in urinary protein and albumin
      losses of 26% and 33%, respectively, without reducing creatinine clearance.
      Albumin synthesis was unchanged and nitrogen balance increased slightly (+142.8
      +/- 85.7 mmol/d [+2.0 +/- 1.2 g/d], P = 0.075). Dietary protein restriction had
      no consistent effect on proteinuria or albuminuria, whereas albumin synthesis
      (25.9 +/- 3.4 v 21.5 +/- 2.9 g/d/1.73 m2, P less than 0.05) and nitrogen balance
      (-135.6 +/- 92.8 mmol/d [-1.9 +/- 1.3 g/d], P = 0.10) decreased. Both therapies
      resulted in a modest increase in plasma potassium concentration. Whether the
      maintenance of albumin synthesis in the presence of a reduction in urinary
      protein losses will convey a long-term advantage to treatment of proteinuric
      patients with angiotensin-converting enzyme inhibitors remains to be determined.

PMID- 1986566
TI  - Survival in patients with end-stage renal disease.
AB  - Based on age and medical condition at the time of treatment, 138 patients
      beginning dialysis for treatment of chronic renal failure between January 1, 1984
      and December 31, 1988, were classified into low, average, and high risk of death.
      The survival in these three groups was shown to be significantly different after
      as little as 6 months. The classification scheme is simple, and can be performed
      at the bedside. Efforts to monitor quality assurance in the dialysis unit must
      account for the significant differences in expected survival that reflect the
      case-mix observed in a particular unit.

PMID- 1986567
TI  - Androgens potentiate the effects of erythropoietin in the treatment of anemia of
      end-stage renal disease.
AB  - Since androgens may increase the sensitivity of the erythroid progenitors to
      erythropoietin, the present studies were designed to investigate the effect of
      administration of androgens on the actions of exogenous erythropoietin (EPO) in
      hemodialysis patients. Studies were performed in a group of 15 adult male
      hemodialysis patients. Seven patients were treated with EPO alone at a dose of
      2,000 U intravenously (IV) three times a week. An additional group of eight
      patients was treated with 2,000 U of EPO three times a week and also received 100
      mg of nandrolone decanoate intramuscularly (IM) each week. After 12 weeks of
      therapy, hematocrit values increased slightly in the group receiving EPO alone,
      from 25.3 +/- 0.8 to 27.4 +/- 1.5. In contrast, EPO in combination with
      nandrolone decanoate resulted in a greater increase in hematocrit values, from
      24.4 +/- 1.4 to 32.9 +/- 1.8 (P less than 0.001). The results show that the
      groups receiving low-dose EPO alone had a poor erythropoietic response. In
      contrast, patients receiving androgen in addition to EPO had a significantly
      greater increase in hematocrit values with treatment. Transfusions were
      eliminated in both groups of patients. These data show that androgen therapy
      significantly augments the action of exogenous EPO such that lower doses of EPO
      are sufficient for an adequate hematopoietic response.

PMID- 1986568
TI  - Inaccurate blood flow rate during rapid hemodialysis.
AB  - Simulated hemodialysis with isotonic saline was performed to compare the
      requested blood flow rate (BFR-r) with the actual blood flow rate (BFR-a)
      delivered during rapid, efficient hemodialysis. Four different blood pumps and
      blood lines from three different manufacturers were used for the studies. BFR-r
      was set on each blood pump, and a timed outflow specimen from the dialysis
      circuit was used to measure the BFR-a delivered. BFR-r values of 200, 350, and
      500 mL/min were used; the arterial pressure was set at -50, -250, and -325 mm Hg.
      BFR was determined every hour for 5 hours. At an arterial pressure of -50 mm Hg,
      the BFR-a was slightly higher than the BFR-r, and this did not vary over the 5
      hour study period. When the arterial pressure was -250 mm Hg, the initial BFR-a
      was 95% of the BFR-r; at the end of the 5-hour study, this had declined to an
      average of 87% of the BFR-r. The largest discrepancy between BFR-a and BFR-r was
      at an arterial pressure of -325 mm Hg; the initial actual values averaged only
      90% of the requested, and by the end of the 5-hour study, this value had declined
      to a mean of 78% of the BFR-r. The use of whole blood with a hematocrit value of
      33% and the addition of venous resistance did not significantly affect these
      results.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1986569
TI  - Successful prophylaxis for fungal peritonitis in patients on continuous
      ambulatory peritoneal dialysis: six years' experience.
AB  - Fungal peritonitis as a serious complication of continuous ambulatory peritoneal
      dialysis (CAPD) is often associated with severe morbidity, CAPD "drop-out" and,
      occasionally, death. Most episodes of fungal peritonitis occur during or after a
      period of antibiotic treatment of various bacterial infections, usually bacterial
      peritonitis. From April 1979 to December 1982 (period I), 10 episodes of fungal
      peritonitis occurred during 415 patient-months, ie, 10.5% of all peritonitis
      episodes recorded in our CAPD program. After the introduction of oral prophylaxis
      with 3 x 500,000 IU [corrected] nystatin during every course of antibiotic
      treatment, only four episodes of fungal peritonitis occurred during 2,102 patient
      months, ie, 3.1% of all peritonitis episodes from January 1983 to March 1989
      (period II). This difference between the first and second periods is significant
      (P less than 0.05). Moreover, none of the four patients who contracted fungal
      peritonitis in the second period received nystatin prophylaxis. Thus, the simple
      measure of oral prophylaxis using this nonabsorbable antifungal agent in every
      case of an antibiotic treatment largely eliminates the risk of fungal peritonitis
      in patients on CAPD.

PMID- 1986570
TI  - Effect of a calcium-entry blocker, nicardipine, on intrarenal hemodynamics in
      essential hypertension.
AB  - The effects of a calcium-entry blocker, nicardipine, on intrarenal hemodynamics
      were studied in essential hypertension. A 4-week study was performed in eight
      patients with essential hypertension who were given a regular sodium diet in the
      first and third weeks, and a sodium-restricted diet in the second and fourth
      weeks. Nicardipine, 60 mg/d, was administered in the third and fourth weeks. The
      urinary sodium excretion rate (UNaV) was plotted on the y-axis against the mean
      arterial pressure (MAP) on the x-axis before and after the administration of
      nicardipine. Assuming the difference between MAP and the x-intercept of this
      renal function curve represents the effective filtration pressure across the
      glomerular capillaries, the intrarenal hemodynamics such as afferent arteriolar
      resistance (RA) and efferent arteriolar resistances (RE), glomerular pressure
      (PG), and gross filtration coefficient (KFG) were calculated. Although the MAP on
      regular salt diet was lowered from 125 +/- 3 to 109 +/- 2 mm Hg by nicardipine,
      neither the renal blood flow rate (RBF) (670 +/- 40 mL/min) nor the glomerular
      filtration rate (GFR) (79 +/- 2 mL/min) was altered. The RA was estimated to be
      reduced from 9,300 +/- 900 to 7,400 +/- 700 dyne.s.cm-5 (P less than 0.01), while
      no changes were noted in RE (4,900 +/- 400 dyne.s.cm-5), PG (50 +/- 1 mm Hg), or
      KFG (0.180 +/- 0.041 [mL/s]/mm Hg). Essential hypertension has been characterized
      by a prominent increase in RA, resulting in maintenance of normal PG. This Ca
      entry blocker worked to normalize intrarenal hemodynamics in essential
      hypertension by dilating afferent arterioles alone.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1986571
TI  - Chemical peritonitis secondary to intraperitoneal vancomycin.
AB  - Although previously reported in the literature, the existence of chemical
      peritonitis due to vancomycin in patients on peritoneal dialysis remains
      controversial. We report four similar episodes of sterile peritonitis in three
      patients receiving intraperitoneal (IP) vancomycin. The prior report implicated a
      change in the brand of vancomycin preparation, from Vancocin to Vancoled, as a
      contributing factor. We noted the occurrence of such episodes following a switch
      from Vancocin to a generic preparation from Abbott Laboratories. High-performance
      liquid chromatographic (HPLC) profiles of the three preparations show Vancocin to
      have a lower level of impurities than the other two; the presence of certain
      contaminants in the other brands may be contributing to the clinical difference
      observed. We conclude that chemical peritonitis due to IP vancomycin
      administration does occur, and that increased awareness of this entity could
      allow other cases to be identified.

PMID- 1986572
TI  - Thrombotic thrombocytopenic purpura with the acquired immunodeficiency syndrome:
      a pathologically documented case report.
AB  - We report a patient with the acquired immunodeficiency syndrome (AIDS) in whom
      the acute onset of neurologic disorders and renal failure could be attributed to
      thrombotic microangiopathy. Clinical, biological, and pathological features were
      compatible with the diagnosis of thrombotic thrombocytopenic purpura (TTP). Such
      cases have been previously described, but histologically documented case reports
      are uncommon.

PMID- 1986573
TI  - Recurrent thrombotic thrombocytopenic purpura associated with membranous
      glomerulopathy.

PMID- 1986575
TI  - Consensus development conference: prophylaxis and treatment of osteoporosis.

PMID- 1986574
TI  - Syncope: 1991.

PMID- 1986576
TI  - Twelve-year incidence of coronary heart disease in middle-aged adults during the
      era of hypertensive therapy: the Framingham offspring study.
AB  - PURPOSE: To provide information on the incidence of coronary heart disease (CHD)
      in the offspring of the original cohort from the Framingham Heart Study. PATIENTS
      AND METHODS: From 1972 to 1974, offspring of the original participants in the
      Framingham Heart Study underwent a baseline examination for standard
      cardiovascular risk factors. At entry into the study, these offspring were 30 to
      59 years old and free of CHD. They were followed for 12 years, during which time
      156 of 1,663 men and 55 of 1,714 women developed CHD. RESULTS: In a multivariate
      proportional hazards model, CHD was significantly associated with age, lower high
      density lipoprotein cholesterol (HDL-C) levels, and number of cigarettes smoked.
      Fasting glucose levels and low-density lipoprotein cholesterol (LDL-C) were
      highly associated with CHD in men, but borderline in women, while triglycerides
      and very-low-density lipoprotein cholesterol were not significantly associated
      with CHD after adjustment for HDL-C and glucose. Blood pressure medication was
      used in half of the hypertensive individuals, and systolic pressure was
      associated with CHD in women only. CONCLUSIONS: This study confirms the
      importance of the common CHD risk factors of cigarette smoking and LDL-C, and
      extends the prognostic role of HDL-C in a middle-aged cohort. The impact of blood
      pressure, with or without use of hypertensive medications, was reduced in this
      study, and the data suggest that this attenuation was due to successful
      treatment.

PMID- 1986577
TI  - Ascites revealing peritoneal and hepatic extramedullary hematopoiesis with
      peliosis in agnogenic myeloid metaplasia: case report and review of the
      literature.
AB  - A 61-year-old man presented with ascites in the course of agnogenic myeloid
      metaplasia (AMM). Ascitic fluid was exudative and contained mature and immature
      leukocytes, erythroid cells, and megakaryocytes as observed on a bone marrow
      smear. Peritoneal biopsy showed myeloid metaplasia, and liver biopsy revealed
      intrasinusoidal myeloid metaplasia and peliosis. Ascites cleared after abdominal
      radiotherapy but treatment resulted in transient aplasia. Subsequently, portal
      hypertension was demonstrated by hepatic transjugular catheterization.
      Complications of splenomegaly led to splenectomy and splenorenal shunt followed
      by fatal acute hepatitis and septic shock. A review of the literature and an
      analysis of mechanisms of ascites occurring in AMM, especially peritoneal
      implants of myeloid tissue and occurrence of peliosis in myeloproliferative
      disorders, are presented.

PMID- 1986578
TI  - Isolated aldosterone deficiency in a patient with autoimmune adrenalitis.

PMID- 1986579
TI  - Simultaneous renal arterial and venous thrombosis associated with idiopathic
      nephrotic syndrome: treatment with intra-arterial urokinase.

PMID- 1986580
TI  - A syndrome resembling thrombotic thrombocytopenic purpura associated with
      Capnocytophaga canimorsus septicemia.

PMID- 1986581
TI  - Malassezia furfur catheter infection cured with antibiotic lock therapy.

PMID- 1986582
TI  - Endothelin and Raynaud's phenomenon.

PMID- 1986583
TI  - Factitious triiodothyronine toxicosis.

PMID- 1986584
TI  - Prognostic factors for Pseudomonas aeruginosa bacteremia.

PMID- 1986585
TI  - Combination therapy versus monotherapy for Pseudomonas aeruginosa bacteremia.

PMID- 1986586
TI  - Nontuberculous mycobacterial rheumatism--fact or fiction?

PMID- 1986587
TI  - Pheochromocytoma in a patient with hyperthyroxinemia.

PMID- 1986588
TI  - Mechanism of glucocorticoid-suppressible hyperaldosteronism.

PMID- 1986589
TI  - Furosemide-131I-hippuran renography after angiotensin-converting enzyme
      inhibition for the diagnosis of renovascular hypertension.
AB  - PURPOSE: We have previously demonstrated the greater sensitivity of 131I-hippuran
      renography than 99mTC-DTPA scintigraphy to diagnose renovascular hypertension
      (RVH). This study assesses the predictive diagnostic value of furosemide-131I
      hippuran renography after angiotensin-converting enzyme (ACE) inhibition in
      patients with and without RVH. PATIENTS AND METHODS: All patients were
      investigated at the University of Miami/Jackson Memorial Medical Center. Twenty
      eight patients had RVH and 22 did not. Twenty-eight patients had normal or
      minimally decreased renal function (serum creatinine level 1.5 mg/dL or less) and
      22 had renal insufficiency (serum creatinine level 1.8 mg/dL or more). Renography
      was performed 60 minutes after oral administration of 50 mg captopril or 10
      minutes after intravenous injection of 40 micrograms/kg enalaprilat. Forty
      milligrams of furosemide were administered intravenously 2 minutes after
      injection of 131I-hippuran. The residual cortical activity (RCA) of 131I-hippuran
      was measured at 20 minutes. RESULTS: RVH was unlikely when RCA after ACE
      inhibition was less than 30% of peak cortical activity. Conversely, RVH was
      present when 131I-hippuran cortical activity steadily increased throughout the
      test to reach 100% at 20 minutes. In azotemic patients with RCA between 31% and
      100%, RVH was differentiated from intrinsic renal disease by obtaining a baseline
      renogram without ACE inhibition and comparing RCA in that study and RCA after ACE
      inhibition. If RCA increased (indicating worsening renal function) after ACE
      inhibition, RVH was likely; whereas, intrinsic renal disease was more likely if
      RCA remained unchanged or decreased (indicating improved renal function) with ACE
      inhibition. The test had a specificity of 95% and a sensitivity of 96% in this
      population. There was a direct correlation between the results of angioplasty or
      surgery on high blood pressure and the changes in RCA before and after
      intervention (n = 20). CONCLUSION: Furosemide-131I-hippuran renography with ACE
      inhibition is highly predictive in identifying patients with RVH.

PMID- 1986590
TI  - Captopril renography in the diagnosis of renal artery stenosis: accuracy and
      limitations.
AB  - PURPOSE: The purpose of this study was to determine the sensitivity, specificity,
      and clinical usefulness of renography performed in combination with captopril
      administration ("captopril renography") in diagnosing renal artery stenosis.
      PATIENTS AND METHODS: Fifty-five patients with suspected renal artery stenosis
      underwent renography prior to performance of renal angiography. Renography was
      performed on two consecutive days using technetium-99m-diethylenetiamine
      pentaacetic acid (DTPA) as an index of glomerular filtration rate and iodine-131
      orthoiodohippurate (OIH) as an index of renal blood flow. Captopril (25 mg
      orally, crushed) was administered 1 hour before the second study. Renal artery
      stenosis was defined as a stenosis exceeding 70%. Renographic criteria were then
      established, retrospectively, to differentiate renal artery stenosis from
      essential hypertension based on (1) asymmetry of function and (2) the presence of
      captopril-induced changes. RESULTS: Renal artery stenosis was detected in 35 of
      55 patients (21 with unilateral and 14 with bilateral stenosis). Three criteria
      were established for diagnosing renal artery stenosis: (1) a percent uptake of
      DTPA by the affected kidney of less than 40% of the combined bilateral uptake,
      (2) a delayed time to peak uptake of DTPA, which was more than 5 minutes longer
      in the affected kidney than in the contralateral kidney, (3) a delayed excretion
      of DTPA, with retention at 15 minutes, as a fraction of peak activity, more than
      20% greater than in the contralateral kidney. The presence of one or more of
      these criteria was diagnostic of renal artery stenosis, with a sensitivity and
      specificity of 71% and 75%, respectively before captopril administration, and 94%
      and 95% after captopril administration. Lesser degrees of asymmetry (i.e., uptake
      of 40% to 50%) had very poor diagnostic specificity. Among patients with
      bilateral stenoses, asymmetry identified the more severely affected kidney, but
      the presence or absence of stenosis in the contralateral kidney could not be
      reliably determined. When pre- and post-captopril studies were compared, the
      presence of captopril-induced scintigraphic changes was a highly specific finding
      for renal artery stenosis, but occurred in only 51% of the cases. OIH
      scintigraphy provided similar results, with slightly lower sensitivity and
      specificity. CONCLUSION: Asymmetry of DTPA uptake, time to peak uptake, or
      retention seen on a single post-captopril renogram is a highly sensitive and
      specific finding in detecting renal artery stenosis but does not distinguish
      unilateral from bilateral disease. If renograms are obtained both before and
      after captopril administration, the presence of captopril-induced change is a
      highly specific finding for the detection of renal artery stenosis, but the
      sensitivity of this finding is low.

PMID- 1986591
TI  - Association of psychiatric manifestations with antibodies to ribosomal P proteins
      in systemic lupus erythematosus.
AB  - PURPOSE: The goal of this study was to determine whether elevated serum levels of
      antibodies to ribosomal P proteins (anti-P antibodies) are associated with
      neuropsychiatric manifestations in patients with systemic lupus erythematosus
      (SLE). Additional experiments examined characteristics of these antibodies that
      might be associated with pathogenicity. PATIENTS AND METHODS: A large number of
      serum samples were collected from patients with SLE, control subjects with other
      rheumatic diseases, and normal individuals. At the time serum samples were
      obtained, patients with SLE were categorized according to the presence of
      psychosis, depression, and other manifestations of central nervous system (CNS)
      involvement. Serum anti-P antibody activity was quantitated by an enzyme-linked
      immunosorbent assay utilizing a synthetic peptide corresponding to the major P
      protein epitope. RESULTS: In a group of 79 normal individuals, mean (+/- SE) IgG
      anti-P activity was 0.01 +/- 0.003 and no individuals had values greater than 3
      SD above the mean. Similar results were obtained measuring IgM anti-P activity.
      Normal levels were found in all sera from 21 patients with rheumatoid arthritis.
      Of 119 patients demonstrating various patterns of antinuclear and anticytoplasmic
      antibody activity, elevated anti-P levels were found only in patients with SLE.
      Overall, 19% of 269 patients with SLE demonstrated elevated levels of IgG or IgM
      anti-P antibodies, including 14% of 187 patients without and 29% of 82 patients
      with neuropsychiatric manifestations. The frequency of positive test results
      varied greatly depending on the nature of the CNS involvement. The frequency in
      patients with severe depression (n = 8) and psychosis (n = 29) was 88% and 45%,
      respectively, compared with only 9% in patients with nonpsychiatric neurologic
      disease (n = 45). For the entire SLE group, the odds ratio for the association of
      anti-P antibodies and severe psychiatric manifestations was 7.63 with a 95%
      confidence interval of 3.61 to 16.14. In a review of 187 patients with SLE
      originally classified as not having severe psychiatric disease, seven of 10
      patients being treated with antidepressant medications had elevated levels of
      anti-P antibodies. In serial studies, the serum level of anti-P antibodies
      appeared to correlate with the activity of psychiatric disease and did not
      correlate with the activity of other manifestations of SLE. Anti-P antibodies in
      nearly all patients were IgG and directed primarily to the C-terminal 11 amino
      acids of the P protein. No difference in these characteristics was observed when
      patients with and without psychiatric manifestations were compared. Paired serum
      and cerebrospinal fluid (CSF) samples were also obtained from eight patients with
      active neuropsychiatric disease. Even when expressed as a fraction of the total
      IgG present, anti-P activity was markedly lower in CSF than in serum.
      CONCLUSIONS: Elevated levels of autoantibodies to the C-terminal region of
      ribosomal P proteins appear to be a specific marker for SLE, and are associated
      with both severe depression and psychosis in this disease. This assay is easily
      reproducible and may help distinguish SLE-induced psychiatric disease from that
      caused by other processes.

PMID- 1986592
TI  - X-linked hypophosphatemia: skeletal mass in adults assessed by histomorphometry,
      computed tomography, and absorptiometry.
AB  - PURPOSE AND PATIENTS AND METHODS: X-linked hypophosphatemia (XLH) is the most
      common inherited form of rickets, yet its influence on skeletal mass in adulthood
      is controversial and incompletely characterized. Accordingly, we measured bone
      mass at several skeletal sites using histomorphometric and radiographic
      techniques in 19 adults (four men) with XLH (age range 20 to 66 years). Most
      subjects had not received medical therapy for XLH since puberty. RESULTS: Eight
      of 14 subjects who underwent transiliac bone biopsy had an elevated cancellous
      bone volume (osteoid and calcified bone), and the group's mean value was
      supranormal (p less than 0.01). Mineralized bone volume, however, was above
      normal in only three subjects (NS). Another measure of trabecular bone density,
      vertebral mineral density by computed tomography, was elevated in three of 13
      subjects, and the mean value of the group was increased (p = 0.05). Integral
      spine bone mineral density (BMD) assessed by dual photon absorptiometry (DPA) was
      elevated in six of 16 subjects, and the mean was also above normal (p less than
      0.01). However, total body calcium, total body BMD (both by DPA), and forearm
      bone mineral content assessed by single photon absorptiometry (predominantly
      cortical bone) were normal in almost all subjects, as were the group means for
      these parameters. Mean regional BMD (by DPA) was below normal in the upper and
      lower limbs (p less than 0.001) and above normal in the spine (p less than 0.005)
      and ribs (p less than 0.01). There was no relationship between these indices of
      bone mass and either biochemical or clinical parameters of disease severity,
      although men tended to have higher z-scores for axial bone density than
      premenopausal women whose values, in turn, tended to be higher than those in
      postmenopausal women (NS). CONCLUSION: We conclude that axial bone mass tends to
      be increased in adults with XLH, sometimes dramatically so, and this is only
      partially attributable to hyperosteoidosis. Peripheral bone mass, however, tends
      to be diminished. Despite these group trends, most adults with untreated XLH have
      normal indices of bone mass as assessed by a variety of techniques at the
      commonly used measurement sites. These findings suggest that "osteoporotic"
      fractures are unlikely to develop as a late complication of XLH in adults.

PMID- 1986593
TI  - Effects of chronic alcohol intake on carbohydrate and lipid metabolism in
      subjects with type II (non-insulin-dependent) diabetes.
AB  - PURPOSE: To study the effects of chronic alcohol intake on carbohydrate and lipid
      metabolism in subjects with non-insulin-dependent (type II) diabetes (NIDDM). To
      also evaluate the effect of alcohol withdrawal on metabolic control. PATIENTS AND
      METHODS: The study group consisted of 46 alcohol-consuming patients with NIDDM
      (NIDDM-B group), 35 non-alcohol-consuming patients with NIDDM (NIDDM group), and
      40 normal control subjects. All patients were admitted to the hospital.
      Carbohydrate and lipid metabolism was assessed in these individuals immediately
      on admission to the hospital and during the following days. RESULTS: In the NIDDM
      B group, blood alcohol (ethyl alcohol) concentration was very low. However,
      chronic alcohol intake was associated with higher fasting and postprandial
      glucose concentrations and higher hemoglobin A1c. No significant differences were
      found in C-peptide levels. Moreover, higher concentrations of 3-hydroxybutyrate
      and free fatty acids were observed in the NIDDM-B group than in the NIDDM group.
      No differences were found in triglyceride concentrations, acid-base patterns, or
      electrolyte levels. The metabolic effects of alcohol completely waned after 3
      days of complete withdrawal. CONCLUSION: Chronic alcohol intake causes
      deterioration in metabolic control of persons with NIDDM. The effects induced by
      alcohol are completely reversed after a few days of withdrawal. Strict metabolic
      assessment is necessary when alcohol is an important constituent of the diet.

PMID- 1986594
TI  - Occupational exposure to HIV: frequency and rates of underreporting of
      percutaneous and mucocutaneous exposures by medical housestaff.
AB  - PURPOSE: To study the frequency of work-related exposures to human
      immunodeficiency virus (HIV)-infected blood and reporting of exposures among
      medical housestaff. SETTINGS: Three teaching hospitals where HIV infection is
      prevalent among patients. SUBJECTS: Internal medicine interns and residents in
      training in 1988-1989. METHODS: In a cross-sectional survey, house officers were
      asked to complete anonymously a questionnaire reviewing their past percutaneous
      and mucocutaneous exposure to blood products. RESULTS: Nineteen percent of the
      respondents (16 of 86) recalled accidental exposure to HIV-infected blood, and
      36% (31 of 86) recalled exposure to blood from patients at high risk for having
      HIV infection. Of the exposures recalled in the 12 months prior to the survey,
      81% (47 of 58) of all needlestick injuries and all (nine of nine) needlestick
      injuries from HIV-infected blood occurred in postgraduate year 1 or 2 trainees.
      Only 30% (31 of 103) of the needlestick injuries recalled by subjects were
      reported. The principal reasons for not reporting were time constraints,
      perception that the percutaneous injury did not represent a significant exposure,
      lack of knowledge about the reporting mechanism, and concern about
      confidentiality and professional discrimination. CONCLUSIONS: Medical housestaff
      are at substantial risk for occupational infection with HIV. A large proportion
      of internal medicine housestaff recall accidental exposure to blood during
      medical school and residency, and the majority of exposures were not reported.
      Hospitals may be able to increase rates of reporting of percutaneous exposures to
      HIV by developing programs that are easy to access, efficient, and strictly
      confidential.

PMID- 1986595
TI  - Diagnostic evaluation of syncope.
AB  - Syncope is a common medical problem and is caused by a wide variety of diseases
      ranging from physiologic derangements with few consequences to conditions that
      may be immediately life-threatening. Because of the large differential diagnosis,
      many diagnostic tests are available for its evaluation. However, a cause of
      syncope is not established in 38% to 47% of patients despite these tests. In
      those patients in whom a diagnosis can be assigned, the history and physical
      examination identify a potential cause in 49% to 85%. Furthermore, in 8% of
      additional patients, history and physical examination are suggestive of causes
      that need confirmation by specific tests. Routine blood tests rarely yield
      diagnostically helpful information. In those patients in whom a potential cause
      for syncope is identified, arrhythmias are diagnosed by electrocardiogram in 2%
      to 11% of patients, cardiac monitoring in 3% to 27% (telemetry or Holter), stress
      test in less than 1%, carotid massage in less than 1%, and electrophysiologic
      studies in less than 3%. Diagnosis of arrhythmias as a cause of syncope is
      problematic because symptomatic correlation during electrocardiographic
      monitoring is rarely found (approximately 4%), and as a result, there is no
      uniform agreement on diagnostic criteria for abnormalities. Similar problems
      exist in the use of electrophysiologic studies. Upright tilt testing and
      psychiatric examination may be useful in evaluation of recurrent syncope of
      unknown cause in patients without organic heart disease. Based on the results of
      recent studies, strategies for evaluation of patients with syncope are possible
      that utilize selective and goal-directed diagnostic testing.

PMID- 1986596
TI  - Maternal postprandial glucose levels and infant birth weight: the Diabetes in
      Early Pregnancy Study. The National Institute of Child Health and Human
      Development--Diabetes in Early Pregnancy Study.
AB  - The cause of macrosomia in the infant of the diabetic woman is still not
      completely defined. The National Institute of Child Health and Human Development-
      Diabetes in Early Pregnancy Study, which recruited insulin-dependent diabetic and
      control women before conception, provided an opportunity to address the
      relationship between maternal glycemia and percentile birth weight. Data were
      analyzed from 323 diabetic and 361 control women. Fasting and nonfasting venous
      plasma glucose were measured on alternate weeks in the first trimester and
      monthly thereafter. Glycosylated hemoglobin was measured weekly in the first
      trimester and monthly thereafter. More infants of the diabetic women were at or
      above the 90th percentile for birth weight than infants of control women (28.5%
      versus 13.1%, p less than 0.001). Although first-trimester nonfasting glucose and
      glycosylated hemoglobin levels were positively correlated with infant birth
      weight (p less than 0.001 and p = 0.008), when the analyses were adjusted for the
      variables of the subsequent trimesters the values became insignificant, whereas
      the third-trimester nonfasting glucose levels adjusted for values in prior
      trimesters emerged as the stronger predictor of percentile birth weight (p =
      0.001). After adjusting for maternal hypertension, smoking, and ponderal index,
      the above relationships remained. In conclusion, monitoring of nonfasting glucose
      levels rather than the fasting levels, which are more commonly monitored in
      clinical practice, are necessary to prevent macrosomia.

PMID- 1986597
TI  - Association between hypothermia and mortality rate of premature infants-
      revisited.
AB  - The incidence of hypothermia (axillary temperature less than 35 degrees C) on
      admission of an infant to a neonatal intensive care unit was retrospectively
      analyzed in 559 very-low-birth-weight (less than 1500 gm) newborn infants. The
      smaller infants were at greater risk of hypothermia. Only in the larger neonates
      was mortality related to hypothermia, which suggests that this known association
      bears little cause-effect relationship.

PMID- 1986598
TI  - Antiepileptic medication in pregnancy: late effects on the children's central
      nervous system development.
AB  - In a follow-up study long-term effects of antenatal exposure to two
      anticonvulsant drugs, phenobarbital and carbamazepine on central nervous system
      development were evaluated. Children aged 6 to 13 years of epileptic mothers who
      used phenobarbital (n = 13), carbamazepine (n = 12), phenobarbital plus
      carbamazepine (n = 12), or no medication (n = 24) during pregnancy were studied.
      None of the mothers had seizures during pregnancy. A control group carefully
      matched for confounding variables was selected of children of nonepileptic
      mothers (n = 61). Minor and major congenital anomalies appeared to be more
      related to mother's epilepsy than to maternal medication. There were no
      neurologic differences between the groups. Exposure to phenobarbital was
      associated with smaller head circumference. An accompanying negative effect of
      phenobarbital on cognitive development was suggested. Further research on this
      intriguing phenomenon seems warranted.

PMID- 1986599
TI  - Multinuclear spermatozoa associated with polyploidy.
AB  - We are reporting on a possible association between multinucleated spermatozoa and
      polyploidy after in vitro fertilization. The semen from the male partner of a
      couple with 40% polyploidy on three in vitro fertilization attempts was examined
      by light and transmission electron microscopy. In that sample 10% to 12% of
      spermatozoa demonstrated conjoined or double heads. The significance of these
      findings is discussed.

PMID- 1986600
TI  - Cross-sectional analysis of triplet birth weight.
AB  - Parameters of fetal growth in triplet gestations are poorly studied and
      controversial. A cross-sectional analysis of triplet birth weight was performed
      to elucidate fetal growth patterns. Birth weight and gestational age data were
      analyzed on 580 infants in 196 triplet sets (eight stillborn infants excluded)
      between 1985 and 1988. Ovulation induction was used in approximately one half the
      gestations and early obstetric and ultrasonographic dating was available in all
      pregnancies. The mean triplet set and individual triplet weights versus
      gestational age were calculated with distinctly linear growth displayed between
      22 to 38 weeks' gestation. Mean intratriplet differences at all gestational ages
      were determined. A comparison of singleton and triplet growth curves was
      constructed to show the distinct growth characteristics of triplets.

PMID- 1986601
TI  - The effects of indomethacin and a beta-sympathomimetic agent on the fetal ductus
      arteriosus during treatment of premature labor: a randomized double-blind study.
AB  - To study the effect of maternal indomethacin or nylidrine hydrochloride treatment
      on the fetus ductus arteriosus and the pulmonary artery, 27 women with threatened
      preterm labor between 24 and 34 weeks' gestation were studied by
      echocardiography. Fourteen women were treated with indomethacin and 13 with
      nylidrin. Both systolic and diastolic velocities in the ductus increased after
      administration of indomethacin indicating constriction in nine fetuses, and
      exceeded the corresponding velocities in the fetuses of the nylidrin group (p =
      0.001). However, there were no changes in pulmonary artery flow velocities (p
      greater than 0.5). In the indomethacin group, there was a significant linear
      positive relationship between the gestational age and the change in ductal flow
      velocity. Three of the nine patients with ductal constriction also had tricuspid
      regurgitation. These findings indicate that indomethacin, not nylidrin, causes
      transient constriction of the ductus arteriosus and the constrictive response
      increases with the gestational age. We recommend echocardiographic surveillance
      of fetal hemodynamics when prostaglandin synthesis inhibitors are used in the
      treatment of spontaneous preterm labor.

PMID- 1986602
TI  - A selective serotonin reuptake inhibitor, fluoxetine hydrochloride, modulates the
      pulsatile release of prolactin in postmenopausal women.
AB  - We investigated serotoninergic regulation of prolactin release in estrogen
      withdrawn postmenopausal women by using a serotonin reuptake inhibitor. Subjects
      underwent frequent blood sampling after placebo (basal) or fluoxetine
      administration. Mean 24-hour serum prolactin concentrations increased
      significantly in response to fluoxetine. Objective pulse analysis revealed no
      change in prolactin pulse frequency with serotoninergic stimulation, but maximal
      serum prolactin peak heights increased significantly. Multiple-parameter
      deconvolution disclosed no change in prolactin half-life, but a significant
      increase in the total mass of prolactin secreted per 24 hours during fluoxetine
      administration. Cosinor analysis of the prolactin time series showed a
      significant increase in the circadian amplitude and mean without any change in
      the time of maximal concentration during treatment with fluoxetine. We conclude
      that short-term activation of the serotoninergic system in the absence of
      substantial estradiol and opiatergic tone significantly increases the secretion
      of prolactin in postmenopausal women.

PMID- 1986603
TI  - Endoscopic sclerotherapy in extrahepatic portal hypertension in pregnancy.
AB  - Extrahepatic portal hypertension usually occurs during childhood, but a
      substantial number of patients may reach adult life. There is a general agreement
      that pregnancy may become hazardous to these patients, and some authors even
      consider this condition as a contraindication to conceiving. A case of endoscopic
      sclerotherapy in such a patient is herein presented, and the approach to such
      patients is discussed.

PMID- 1986604
TI  - Heterotopic pregnancies after in vitro fertilization and embryo transfer.
AB  - Seventeen cases of heterotopic pregnancies are reported among 1648 clinical
      pregnancies after in vitro fertilization. The high prevalence of tubal damage
      among IVF patients and the use of superovulation and multiple embryo transfer
      might predispose patients to the condition. Nine patients reported abdominal pain
      and vaginal bleeding, five patients did not have symptoms, and three had acute
      abdominal emergencies. Transvaginal ultrasonography was superior to
      transabdominal ultrasonography in the diagnosis of extrauterine pregnancies. The
      presence of an intrauterine gestation sac in a patient without symptoms should
      not exclude the diagnosis of a concomitant extrauterine pregnancy until the
      pelvis is carefully visualized. Early diagnoses of viable ectopic pregnancies
      before rupture abolishes mortality and morbidity and offers the chance of patient
      selection for conservative treatment. In two patients the extrauterine gestation
      sac was treated by transvaginal aspiration and injection of potassium chloride
      under ultrasonographic guidance. The outcome of the intrauterine pregnancy was
      favorable regardless of the method of treatment of the ectopic pregnancy.

PMID- 1986605
TI  - A risk-benefit analysis of elective bilateral oophorectomy: effect of changes in
      compliance with estrogen therapy on outcome.
AB  - A bilateral oophorectomy at the time of elective hysterectomy is often performed
      to prevent ovarian cancer. The assumption that endogenous estrogen can be easily
      replaced with supplemental medication fosters the decision for routine
      oophorectomy. Published reports on the use of postmenopausal estrogen indicate
      that compliance is less than perfect. This fact could affect the overall outcome.
      Decision analysis techniques with Markov cohort modeling were used to evaluate
      the policy of elective bilateral oophorectomy. Results from studies judged
      methodologically sound were combined to determine values representing the
      influence of estrogen on coronary heart disease, breast cancer, and osteoporotic
      fracture. The decision tree also explicitly incorporated patient compliance. When
      compliance with estrogen therapy is assumed to be perfect, oophorectomy yields
      longer life expectancy than retaining the ovaries. When actual drug-taking
      behavior is considered, retaining the ovaries results in longer survival. This
      analysis highlights the importance of including the effects of patient compliance
      with treatment recommendations when the impact of a health policy decision such
      as prophylactic surgery is assessed.

PMID- 1986606
TI  - Spontaneous and steroid-induced recurrence of endometriosis after suppression by
      a gonadotropin-releasing hormone antagonist in the rat.
AB  - Recurrent endometriosis in women is difficult to study because of the ethical
      consideration of performing repeated surgeries. Previously in the rat model we
      described therapeutic regression of endometriosis with the gonadotropin-releasing
      hormone antagonist antide. Presently we report the spontaneous and steroid
      induced recurrence of endometriosis after withdrawal from antide therapy. Rats
      with endometriosis received antide or vehicle on days 0 (proestrus), 3, 6, and 9
      and were killed on days 0, 6, 12, 18, 24, 30, and 42 (n = 4 antide-treated and 4
      vehicle-treated rats killed per day). Additional antide-treated rats (n = 4 per
      treatment) received estrogen, progesterone, both estrogen and progesterone,
      cholesterol, and no steroid on day 9 and were killed on day 12. Antide
      significantly suppressed endometriotic implant size on days 12, 18, and 24.
      However, implant size spontaneously returned to pretreatment values by day 30.
      Administration of steroids on day 9 elicited regrowth of antide-suppressed
      endometriosis (estrogen plus progesterone greater than estrogen, progesterone, or
      cholesterol greater than no steroid) by day 12. This resilience of endometriosis
      offers an explanation for treatment failure and recurrence of the disease in
      women.

PMID- 1986607
TI  - Diastolic circulatory dynamics in the presence of elevated placental resistance
      and retrograde diastolic flow in the umbilical artery: a Doppler echographic
      study in lambs.
AB  - To evaluate the effects of elevated placental resistance on the diastolic blood
      flow in the main arteries of the fetus, placental resistance was mechanically
      increased in six exteriorized lambs. A string was inserted into the exposed
      section of the umbilical cord and placed around the veins isolating them from the
      arteries. Doppler flow velocities waveforms were measured by placing a
      lightweight acoustic bag on the umbilical cord. Placental resistance was
      increased by tightening the string until retrograde diastolic flow was observed
      in the umbilical artery. All measurements were obtained within 10 minutes. Heart
      rate, PO2, PCO2, and pH before umbilical vein compression were 177 +/- 24
      beats/min, 16.4 +/- 1.8 mm Hg, 42.5 +/- 4 mm Hg, and 7.3 +/- 0.05, respectively,
      and 112 +/- 38 beats/min, 5.9 +/- 1.5 mm Hg, 56.6 +/- 7.0 mm Hg, and 7.2 +/-
      0.05, respectively, after umbilical vein compression. The patterns of diastolic
      flow observed after compression were descending aorta, retrograde; aortic arch,
      retrograde; ascending aorta, bidirectional; cephalic aorta, forward, which were
      quite different from their respective baseline patterns. It is concluded that the
      appearance of reverse diastolic flow in the umbilical artery indicates that (1)
      the lowest vascular resistance in the fetal circulatory network is no longer at
      the placental but at the cerebral level, and (2) preplacental blood with low
      oxygen content from the descending aorta and pulmonary artery is being shifted
      toward the brain.

PMID- 1986608
TI  - Blood pressure self-monitoring during pregnancy: practical considerations.
AB  - Portable electronic and mechanical aneroid instruments for blood pressure self
      monitoring are available, inexpensive, and reasonably accurate. Instructing the
      patient at risk for borderline, mild hypertension or chronic hypertension during
      pregnancy on self-monitoring of blood pressure has advantages. Combined with
      conventional office measurements, many daily recordings give an accurate picture
      of an individual's dynamic blood pressure. Lower blood pressures commonly found
      outside the office are likely attributable to an increased awareness, less
      anxiety, and attention by the patient to nonpharmacologic factors. Such persons
      may well avoid antihypertensive therapy or antepartum hospitalization. This
      information provides a strong incentive to undertake and adhere to an appropriate
      plan of treatment for those patients whose hypertension is confirmed by blood
      pressure self-monitoring technique. We consider blood pressure self-measurement
      to complement other reported monitoring techniques for active patient
      participation at home or in the work setting. It also permits an early evaluation
      of blood pressure alterations to rule out preeclampsia, especially in the
      pregnant patient with chronic essential hypertension.

PMID- 1986609
TI  - Forskolin and methotrexate induce an intermediate trophoblast phenotype in
      cultured human choriocarcinoma cells.
AB  - The human placenta and its associated membranes are vital to the maintenance,
      nutrition, and protection of the developing fetus. During placental development
      some cytotrophoblasts give rise to the chorionic membrane whereas others fuse to
      form a differentiated syncytium of cells that are responsible for placental
      protein and steroid hormone production. The mechanisms involved in the
      differentiation of the trophoblasts are unknown; however, an intermediate stage
      with a characteristic phenotype has been documented in vivo. We have observed
      that chemically dissimilar xenobiotic agents induced BeWo choriocarcinoma cells
      to change their usual cytotrophoblastic phenotype and acquire morphologic and
      functional characteristics typical of intermediate trophoblast. Incubation of
      BeWo cell cultures in the presence of 1 mumol/L methotrexate for 48 hours
      stimulated human chorionic gonadotropin secretion (2.3-fold) and aromatase
      activity (4.9-fold). Morphologic findings associated with these hormonal changes,
      including increased nuclear size and cytoplasmic expansion, were also observed.
      With the use of a computer-interfaced image analyzer, planimetric morphometry of
      the nuclear area of the cells revealed a 1.8-fold increase after incubation with
      methotrexate. The effect of forskolin, a direct activator of adenylyl cyclase,
      was also evaluated by means of this model of cytotrophoblast differentiation. The
      addition of 10 mumol/L forskolin to BeWo cultures also resulted in dramatic
      changes in trophoblast cell phenotype. Increases in human chorionic gonadotropin
      synthesis (7.3-fold), aromatase activity (13.5-fold), and nuclear area (3.0-fold)
      were induced over those of untreated cells. In addition, increases in
      [3H]thymidine incorporation (1.7-fold) were afforded by both treatments. These
      results suggest that biochemical and cytologic changes associated with human
      trophoblast differentiation can be induced in vitro via activation of the
      adenylyl cyclase pathway by forskolin and through unknown and apparently
      independent signals by methotrexate.

PMID- 1986610
TI  - Factors influencing the initiation of nonshivering thermogenesis.
AB  - The aim of this study was to observe the sequential effects of oxygenation,
      umbilical cord occlusion, and finally cooling on circulating catecholamines and
      nonshivering thermogenesis in fetal sheep. We studied five fetal sheep at 132 +/-
      3 days' gestation. The fetuses were first ventilated with oxygen; PaO2 levels
      were maintained above 150 mm Hg, and by 60 minutes there was a significant rise
      in both plasma glycerol and free fatty acid levels. After umbilical cord
      occlusion there was a peak in plasma catecholamine and triiodothyronine levels
      but no significant increase in lipolysis. Cooling, by circulating cold water
      through a coil around the fetus, induced maximum lipolysis and temperature
      difference between brown fat and body core, when plasma catecholamine levels were
      falling. During this study the changes in plasma catecholamine levels did not
      correlate with the onset of nonshivering thermogenesis. Cutaneous cooling, which
      causes neurally mediated sympathetic stimulation of brown adipose tissue, is the
      major signal for the initiation of nonshivering thermogenesis and thus neonatal
      adaptation.

PMID- 1986611
TI  - Early neonatal mortality and cesarean delivery in Mexico City.
AB  - The relationship between cesarean delivery and neonatal mortality is presented
      with information from 292 early neonatal deaths (cases) and 3098 survivors
      (controls) born in 25 hospitals in Mexico City during the summer of 1984. The
      overall rate of cesarean delivery was 27%. Variations between health agencies and
      different social groups were not related to obstetric risk, suggesting that a
      sizable proportion of the operations were probably unjustified. Babies of normal
      birth weight (greater than or equal to 2500 gm) delivered by cesarean section
      were 2.5 times more likely to die in the early neonatal period compared with
      vaginally delivered babies of the same weight. The excess of mortality could not
      be explained by the effect of maternal characteristics or complications or by
      differences in birth weight or gestational age. It is suggested that the
      conditions under which the operation was performed probably explain the increased
      risk of early neonatal death. It is likely that poor quality of resuscitation and
      respiratory care are implicated in the link between "unnecessary" cesarean
      section and early neonatal mortality.

PMID- 1986612
TI  - Methotrexate treatment of tubal pregnancy.

PMID- 1986613
TI  - Nonimmune hydrops in fetal Niemann-Pick disease.

PMID- 1986614
TI  - Chlamydial infection and pregnancy outcome.

PMID- 1986615
TI  - Budd-Chiari syndrome, obstetric complications, and antiphospholipid antibodies.

PMID- 1986616
TI  - Was there really a difference with amnioinfusion?

PMID- 1986617
TI  - Coagulation changes on natural estrogens.

PMID- 1986618
TI  - High CA 125 levels and spontaneous abortion.

PMID- 1986619
TI  - Amniotic endothelin increase during pregnancy.

PMID- 1986620
TI  - The effect of tetracycline on levels of oral contraceptives.
AB  - Despite the widespread use of tetracycline for treatment of dermatologic
      disorders and sexually transmitted diseases, the pharmacodynamics of oral
      contraceptive use in the presence of tetracycline has not been studied. Seven
      normal women ingested an oral contraceptive containing ethinyl estradiol 35
      micrograms and norethindrone 1 mg in the follicular phase of the menstrual cycle.
      On day 0 baseline ethinyl estradiol and norethindrone levels were obtained at 0,
      1/2, 3/4, 1, 2, 4, 12, and 24 hours after oral contraceptive administration. On
      day 1 tetracycline 500 mg was given orally every 6 hours while the oral
      contraceptive was continued. Tetracycline, ethinyl estradiol, and norethindrone
      levels were determined at the same time intervals as on day 0. Oral contraceptive
      and tetracycline were continued for up to 10 days, and additional concentrations
      of ethinyl estradiol, norethindrone, and tetracycline were determined between
      days 5 and 10. Four additional normal women ingested tetracycline for 5 to 10
      days. Tetracycline levels were determined at the time intervals noted above on
      day 1 and days 5 to 10. No significant decrease in plasma ethinyl estradiol or
      norethindrone concentration was seen with either short-term (24 hours) or long
      term (5 to 10 days) ingestion of tetracycline. Similarly, levels of tetracycline
      do not significantly decrease with ingestion of a low-dose oral contraceptive.

PMID- 1986621
TI  - Venous Doppler ultrasonography in the fetus with nonimmune hydrops.
AB  - Eighteen pregnancies with nonimmune hydrops fetalis were referred for fetal
      echocardiography to rule out congenital heart disease. In 14 of these cases,
      pulsating blood velocities were recorded in the umbilical vein, which in a normal
      population had a nonpulsatile blood velocity pattern. The four cases without
      pulsations in the umbilical vein were found to have intrauterine viral
      infections. In the last 10 cases examined, the umbilical venous pulsations were
      found to reflect abnormal central venous pulsations during atrial systole
      suggesting increased fetal central venous pressure. Right ventricular shortening
      fraction was significantly decreased in the group with umbilical venous
      pulsations compared with those without (0.18 versus 0.32, p less than 0.05). All
      the fetuses without venous pulsations survived, but only four of the 14 with
      pulsations survived (p less than 0.05). The results suggest that blood velocity
      recordings in the umbilical and central veins of the fetus can give valuable
      clinical information with regard to the presence of fetal congestive heart
      failure and differentiate between this physiologic state and other causes of
      nonimmune hydrops fetalis. This may have implications for fetal diagnostic work
      up and prognosis.

PMID- 1986622
TI  - The relationships among umbilical artery velocimetry, fetal biophysical profile,
      and placental inflammation in preterm premature rupture of the membranes.
AB  - The relationships among umbilical artery velocimetry, fetal biophysical profile,
      and placental inflammation in 44 consecutive patients with preterm premature
      rupture of the membranes were determined. All patients were followed up with
      daily fetal biophysical profiles and systolic/diastolic ratios. After delivery,
      placental pathologic examination for histologic evidence of infection (umbilical
      vasculitis) was performed in all cases according to a standard protocol. The
      longitudinal trends of fetal biophysical profile scores and systolic/diastolic
      ratios were analyzed for patients with and without umbilical vasculitis. Analysis
      of the longitudinal trend during the period of 2 to 7 days before delivery showed
      that there were no differences of biophysical scores of systolic/diastolic ratios
      in either group. However, in the last examination, within 24 hours of delivery,
      patients with umbilical vasculitis had higher systolic/diastolic ratios and lower
      biophysical profile scores as compared with previous examinations. In addition,
      the biophysical profile score of the last examination 24 hours before delivery in
      patients with umbilical vasculitis was found to be significantly lower as
      compared with patients without umbilical vasculitis (mean +/- SD, 6.6 +/- 2.3
      versus 8.2 +/- 2.4, respectively). These data suggest that subclinical stages of
      infection are associated with biophysical alterations of the fetoplacental unit
      (i.e., simultaneous decrease in fetal biophysical activities and increase in
      systolic/diastolic ratios). Daily umbilical artery systolic/diastolic ratios, in
      conjunction with biophysical profiles, may be useful to follow up patients with
      preterm premature rupture of the membranes.

PMID- 1986623
TI  - Endometriosis associated with massive ascites and absence of pelvic peritoneum.
AB  - Although massive ascites associated with endometriosis has been reported in rare
      cases, this patient was also noted to have massive destruction of the pelvic
      peritoneum. Failure of medical suppression necessitated total abdominal
      hysterectomy and bilateral salpingo-oophorectomy. Several months after surgery
      ascites resolved, possibly with reestablishment of the pelvic peritoneum.

PMID- 1986624
TI  - Endometrial thickness as measured by endovaginal ultrasonography for identifying
      endometrial abnormality.
AB  - Diagnostic curettage has for many years been the method of choice to diagnose
      endometrial cancer in women with postmenopausal bleeding. The costs for curettage
      performed today are huge, and approximately only 10% in this group of women will
      be diagnosed with endometrial cancer. Thus less expansive techniques to obtain
      endometrial samples have been evaluated, but all of them are invasive. The value
      of endovaginal ultrasonography for identifying endometrial abnormality in this
      group of women has not been evaluated until now. This study used endometrial
      thickness as measured by endovaginal ultrasonography as an indicator of
      endometrial abnormality. It was demonstrated in 205 women with postmenopausal
      bleeding that if the endometrium was less than 9 mm thick, no endometrial cancer
      was found at curettage. The mean endometrial thickness in those women with
      endometrial cancer was 18.2 +/- 6.2 mm as compared with 3.4 +/- 1.2 mm in those
      women with atrophic endometrium. If the cutoff limit for endometrial abnormality
      was 5 mm, the positive predictive value for identifying endometrial abnormality
      was 87.3%. If this limit had been used in this study, 70% of the curettage
      procedures could have been avoided.

PMID- 1986625
TI  - The use of the Cytobrush cervical sampler in patients with cervical stenosis.
AB  - In 37 of 43 patients (86%) with cervical stenosis (inability to undergo passage
      of the cotton-tipped applicator), the Cytobrush cervical sampler was successfully
      passed into the endocervical canal. The use of the Cytobrush sampler for cervical
      cytologic screening appears to be valuable in patients with cervical stenosis.

PMID- 1986626
TI  - Successful antepartum treatment of listeriosis.
AB  - A pregnant patient had a flulike illness at 27 weeks. Listeria monocytogenes
      infection was diagnosed by blood cultures. Electronic monitoring suggested the
      fetus was stressed. Use of tocolytics inhibited uterine contractions while the
      mother was treated with intravenous ampicillin. Four days later when labor began
      because of chorioamnionitis, the infant was delivered in good condition.

PMID- 1986627
TI  - Anemia and spontaneous preterm birth.
AB  - The association between anemia during pregnancy and spontaneous preterm birth was
      studied with a two-stage case-control design in a large, multiethnic cohort.
      Results of all hematologic measurements were abstracted from the prenatal and
      delivery records of 1706 of the 26,901 women in the cohort. Among women delivered
      of infants at term, mean hematocrit value was low during the early phase of the
      second trimester, stable until near term, then reached a maximum at 40 weeks'
      gestation. The mean hematocrit value of black women was consistently lower than
      that of Asian, Mexican, and white women. Anemia (hematocrit value less than the
      tenth percentile for ethnic group and duration of pregnancy) at any time during
      the second trimester was positively associated with subsequent spontaneous
      preterm birth (odds ratio, 1.9; 95% confidence interval, 1.3 to 2.8). Compared
      with white women, the odds ratios for preterm birth were 2.0 (95% confidence
      interval, 1.6 to 2.4) for black, 1.2 (95% confidence interval, 0.9 to 1.6) for
      Asian, and 1.2 (95% confidence interval, 1.0 to 1.5) for Mexican women.
      Adjustment for second-trimester anemia had minimal influence on the odds ratios.
      We conclude that anemia during the second trimester was associated with preterm
      birth. However, it does not account for the large ethnic differences in preterm
      birth.

PMID- 1986628
TI  - Fetal urine output does not influence residual amniotic fluid volume after
      premature rupture of membranes.
AB  - Fetal urine production in 12 women with premature rupture of membranes did not
      differ from that of a control group, and there was no correlation between fetal
      urine output and residual amniotic fluid volume. Residual amniotic fluid volume
      after premature rupture of membranes does not appear to depend on or alter fetal
      renal function.

PMID- 1986629
TI  - The diagnosis of ovarian cancer by pathologists: how often do diagnoses by
      contributing pathologists agree with a panel of gynecologic pathologists?
AB  - The Cancer and Steroid Hormone Study, a multicenter, population-based, case
      control study of ovarian, breast, and endometrial cancer in women 20 to 54 years
      of age, permitted the diagnoses of contributing pathologists to be compared with
      those of a panel of three gynecologic pathologists. A diagnosis of ovarian cancer
      was made by contributing pathologists on 477 subjects. Agreement between the two
      groups of pathologists was 97% for primary epithelial ovarian cancer and 89% for
      primary nonepithelial ovarian malignancies. Agreement on diagnosis of major
      cellular subtypes of ovarian malignancy ranged between 73% for endometrioid
      cancer and 100% for clear cell carcinomas. We conclude that the diagnosis of
      pathologic features of primary ovarian cancer is highly predictable. Nonetheless,
      diagnosis by histologic type varies sufficiently that a review process should be
      considered for clinical or investigative decisions involving specific histologic
      diagnoses of ovarian cancer.

PMID- 1986630
TI  - Dissection of the cardinal ligament in radical hysterectomy for cervical cancer
      with emphasis on the lateral ligament.
AB  - Surgical experience with carcinomas of the uterus and rectum has provided new
      insights into the surgical anatomy of a lamina, which separates the paravesical
      space from the pararectal space. It has been proved that each of the lamina
      consists of the cardinal and lateral ligaments and pelvic splanchnic nerves,
      descending in the following order. The cardinal and lateral ligaments, as a
      connective stalk, insert into the lateral walls of the uterus and rectum
      extending from the inner aspect of the pelvic wall. Clarification of this
      structural relationship led to the development of a new procedure for the
      dissection of the cardinal ligament in radical hysterectomy, while still
      preserving the lateral ligament. This facilitated systematic dissection of the
      cardinal and uterosacral ligaments with posterior manipulation, leading to a
      reduction in blood loss and to prevention of brisk bleeding from the venous
      plexuses.

PMID- 1986631
TI  - Spontaneous ovarian-to-vaginal fistula: a case report.

PMID- 1986632
TI  - Argon laser versus microscissors for hysteroscopic incision of uterine septa.
AB  - We performed hysteroscopic metroplasty in 21 women with repeated abortion and
      subseptate uterus. The patients were randomly allocated to septal incision with
      the argon laser (group I, 10 subjects) or microscissors (group II, 11 subjects)
      to compare these instruments in terms of surgical feasibility and anatomic
      results. The mean operating time was 57% longer in group I than in group II (p =
      0.001), the intra- and postoperative morbidity of the whole series was
      negligible, and the anatomic results at abdominal ultrasonography and
      hysteroscopy performed 2 months postoperatively were similar in the two groups.
      This study confirms that microscissors are the simplest, fastest, most effective,
      and least expensive instrument to correct a septate uterus. The complete
      agreement of the findings at follow-up hysteroscopy and ultrasonography suggest
      the use of the latter as the method of choice to check the surgical results.

PMID- 1986633
TI  - Quantitative and qualitative platelet abnormalities during pregnancy.
AB  - In a 1-year period, 15 of 4048 pregnant women were found to have thrombocytopenia
      during their first prenatal visit. Their qualitative and quantitative platelet
      abnormalities were followed up prospectively for 1 to 6 months post partum.
      Platelet counts returned to normal in 14 of 15 patients 4 to 6 weeks post partum.
      von Willebrand factor antigen and ristocetin cofactor activity were low in three
      of 15 patients 4 to 6 weeks post partum, but had been normal during the
      antepartum period. Two of these three patients had prolonged bleeding times ante
      partum and post partum. All three patients subsequently were found to have mild
      type I von Willebrand disease. Six patients had detectable platelet antibodies.
      Neonatal thrombocytopenia was found in one term infant of a patient with mild
      thrombocytopenia and negative platelet antibodies. This study suggests that mild,
      transient, isolated thrombocytopenia can occur in an otherwise normal pregnancy
      and its incidence may be lower than previously reported. Extensive testing is not
      indicated unless there is an associated prolonged bleeding time. The possibility
      of von Willebrand disease or a qualitative platelet disorder should be
      considered.

PMID- 1986634
TI  - The clinical implications of subchorionic placental lucencies.
AB  - Forty-six patients were identified at a perinatal diagnostic referral center as
      having subchorionic placental lucencies. These lucencies varied from simple to
      multicystic and covered up to 50% of the subchorionic placental surface. Clinical
      follow-up of 40 patients demonstrated no increase in the incidence of adverse
      pregnancy outcome. We conclude that these pregnancies are not at higher risk when
      the subchorionic placental lucencies are not associated with other intraplacental
      or fetal anomalies.

PMID- 1986635
TI  - Magnesium, anesthesia, and hemodynamic control.

PMID- 1986636
TI  - Spinal anesthesia: significant prolongation of the pharmacologic effect of
      tetracaine with lipid solution of the agent.
AB  - A novel approach for increasing the duration of anesthesia after a single
      subarachnoid injection of a local anesthetic is presented. Tetracaine 1% 0.5
      mg/kg was administered in 10% glucose or in lipid solution (iophendylate) in two
      groups of rabbits via catheters chronically implanted in the subarachnoid space.
      The pharmacologic effect was assessed by evaluation of the intensity and duration
      of the motor blockade according to a three-stage scale. Significant prolongation
      (447 +/- 13 min vs. 130 +/- 7 min, P less than 0.01) with a moderate decrease in
      the intensity of the motor blockade was observed with lipid solution as compared
      to the aqueous solution. This effect is attributed to the slow release of the
      agent from the lipid phase, which actually functions as a drug depot in the
      cerebrospinal fluid. The proposed method is suggested as an additional approach
      for the development of drug delivery system intended for prolongation of spinal
      anesthesia.

PMID- 1986637
TI  - Alterations in collateral blood flow produced by isoflurane in a chronically
      instrumented canine model of multivessel coronary artery disease.
AB  - The actions of isoflurane and adenosine on left ventricular myocardial perfusion
      during a total occlusion of the left anterior descending coronary artery and
      concomitant stenosis of the left circumflex coronary artery were investigated in
      dogs chronically instrumented for measurement of systemic and coronary
      hemodynamics, regional myocardial contractile function (via ultrasonic
      sonomicrometers), and myocardial blood flow (via the radioactive microsphere
      technique). An Ameroid constrictor was implanted on the left circumflex coronary
      artery to produce a slowly progressive stenosis that gradually depleted the
      coronary reserve of the distal vascular bed. The reductions in reserve were
      evaluated by daily measurement of baseline left circumflex coronary blood flow
      velocity and the hyperemic response to injection of adenosine. At a stage of
      moderate or severe left circumflex stenosis development, the left anterior
      descending coronary artery was totally occluded via a hydraulic occluder to
      simulate multivessel coronary artery disease, and control measurements of
      hemodynamics, regional contractile function, and myocardial blood flow were
      completed. In separate groups of experiments, either adenosine (0.64 and 1.28
      mg/min) or isoflurane (1.6-1.8 and 2.3-2.5%, end-tidal) was administered and
      measurements remade during steady state hemodynamic conditions. Finally,
      diastolic aortic pressure and heart rate were adjusted to levels present in the
      control state during administration of adenosine or isoflurane, and additional
      measurements were recorded. Isoflurane reduced mean arterial pressure, left
      ventricular systolic pressure, and the rate of increase of left ventricular
      pressure at 50 mmHg (positive dP/dt50) without change in heart rate.
      Administration of isoflurane decreased blood flow in normal, stenotic, and
      occluded regions; however, when arterial pressure and heart rate were restored to
      levels present in the conscious state, myocardial perfusion in all regions was
      maintained at control levels. Ratios of flow between occluded and normal or
      stenotic zones remained unchanged from the conscious state during a constant
      aortic pressure and heart rate. Similar results were obtained in dogs with either
      a moderate or severe left circumflex coronary artery stenosis. In contrast,
      adenosine produced a dose-related decrease in collateral flow and occluded-to
      normal or occluded-to-stenotic zone flow ratio. The results of this investigation
      indicate that adenosine but not isoflurane redistributes blood flow away from
      collateral-dependent myocardium to other regions in a chronically instrumented
      canine model of multivessel coronary artery disease.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 1986638
TI  - Myocardial epinephrine sensitization with subanesthetic concentrations of
      halothane in dogs.
AB  - The authors investigated myocardial epinephrine sensitization by subanesthetic
      concentrations of halothane. The dose-response relationship for the action of
      halothane was examined with etomidate plus varying subanesthetic concentrations
      of halothane in dogs. The arrhythmogenic threshold of epinephrine was decreased
      in a dose-dependent manner at end-tidal concentrations of halothane between 0.1
      and 0.3%. At end-tidal halothane is greater than 0.3%, and no further reduction
      of arrhythmogenic threshold of epinephrine occurred. The plasma concentrations of
      epinephrine producing four or more premature ventricular contractions in 15 s
      were 201.3 +/- 34.3, 98.1 +/- 13.9, 60.3 +/- 8.63, 57.9 +/- 12.8, 54.5 +/- 8.61,
      and 53.9 +/- 4.86 ng/ml (mean +/- SEM), at 0, 0.1, 0.3, 0.5, 1.0, and 1.5% of
      halothane at end-tidal concentrations, respectively. The results suggest that in
      the presence of etomidate, halothane produces myocardial sensitization to
      epinephrine at subanesthetic concentrations as low as 0.1%. Increasing halothane
      to 0.3% produces a further reduction in the arrhythmogenic dose of epinephrine.

PMID- 1986639
TI  - Effects of halothane on delayed afterdepolarization and calcium transients in dog
      ventricular myocytes exposed to isoproterenol.
AB  - The effects of halothane on isoproterenol-induced delayed after-depolarizations
      (DADs) were investigated in canine ventricular myocytes. In addition, the effects
      of halothane on the intracellular free calcium transient were determined in fura
      2-loaded myocytes exposed to isoproterenol to explore the mechanisms underlying
      halothane effects on DADs. Isoproterenol (100 nM) induced DADs and/or undriven
      action potentials in myocytes stimulated electrically with the use of trains of
      10 stimuli delivered at basic drive cycle lengths of 200-1,000 ms. Isoproterenol
      (100 nM) increased the peak ratio (350/380 nm excitation) of stimulated myocyte
      calcium transients; furthermore, isoproterenol induced a second spontaneous
      component in the calcium transients of 62% of treated myocytes (n = 72).
      Halothane (1.5%, 0.53 mM) significantly decreased the amplitude of isoproterenol
      induced DADs (P less than 0.01). Halothane not only reduced the peak ratio of the
      stimulated calcium transient, but also eliminated the second spontaneous
      component in myocytes previously exposed to isoproterenol (n = 14). Elevated
      extracellular calcium concentrations (5 mM) restored the amplitudes of DADs and
      the second components of the calcium transients in myocytes exposed to
      isoproterenol and halothane. These data suggest that halothane opposes
      isoproterenol-induced DADs by altering intracellular calcium stores. The authors'
      findings do not support a role for DAD-induced triggered activity in the genesis
      of anesthetic-catecholamine dysrhythmias.

PMID- 1986640
TI  - Body position changes redistribute lung computed-tomographic density in patients
      with acute respiratory failure.
AB  - Ten patients with parenchymal acute respiratory failure (ARF) underwent computed
      tomography (CT) scans while in the supine and prone positions. At equal levels of
      positive end-expiratory pressure, the authors measured the changes of CT density
      in dorsal and ventral basilar lung regions induced by the change of position as
      well as alterations of gas exchange. The level of venous admixture did not change
      with body position. The CT scan image of each lung was fractionated into ten
      levels from dorsal to ventral, each constituting 10% of the lung height. After
      measuring each lung fraction, the volume, the average CT number, its frequency
      distribution, and the expected normal value, we computed the lung tissue mass,
      the excess tissue mass, and the fraction of normally inflated tissue (excess
      tissue mass = amount of "tissue," which includes edema, cells, and blood in
      excess of the expected normal value). We also estimated the superimposed
      hydrostatic pressure on each lung region. We found that the excess lung tissue
      mass is independent of position. However, in patients in the supine position,
      lung CT density increased and regional inflation decreased from ventral to
      dorsal, suggesting progressive deflation of gas-containing alveoli along the
      gravity gradient. A similar ventral-dorsal deflation pattern occurred within 10
      min in patients in the prone position. We conclude that the lung in patients with
      ARF behaves like an elastic body with a diffusely increased mass; dependent lung
      regions are compressed by the pressure of overlying structures.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1986641
TI  - Volatile anesthetics depress calcium channel blocker binding to bovine cardiac
      sarcolemma.
AB  - Volatile anesthetics produce their negative inotropic effect on the heart mainly
      by interference with calcium homeostasis in the myocardial cell. In order to
      elucidate the mechanism of the depression, we have evaluated the effect of the
      volatile anesthetics on the binding of the calcium channel blocker
      [3H]nitrendipine to purified bovine cardiac sarcolemma. The radioligand binding
      studies were carried out at 25 degrees C, with increasing concentrations of
      [3H]nitrendipine (0.01-1 nM), in the presence or absence of unlabeled
      nitrendipine to determine specific binding, and with or without 1.9% halothane,
      2.3% isoflurane, and 4.8% enflurane. Separately, [3H]nitrendipine was measured in
      the presence of increasing doses of halothane (0.78, 1.33, 1.90, and 2.57%).
      Kinetic studies of association and dissociation rate were performed with 1.90%
      halothane and 1 nM [3H]nitrendipine at different time intervals. All three
      volatile anesthetics produced depression of [3H]nitrendipine binding to the
      isolated cardiac sarcolemma. Only halothane produced a significant depression in
      binding, ranging between 59 and 66% (P less than 0.05), depending on the
      concentration of [3H]nitrendipine used. Isoflurane produced 29-38% depression,
      and enflurane produced 5-22% depression. Halothane also produced a significant (P
      less than 0.01) dose-dependent decrease in [3H]nitrendipine-specific binding. The
      kinetic binding experiments demonstrated that the time course for halothane's
      effect on association and dissociation of [3H]nitrendipine was 5 min for the half
      maximum effect; the maximal reduction in binding capacity was at 15-30 min (P
      less than 0.05). Scatchard analysis revealed that all three volatile anesthetics
      produced reduction in the maximal number of binding sites; however, they varied
      in their effect on binding affinity. Only halothane produced a homogenous
      increase in the dissociation constant, signifying reduced affinity of the Ca2+
      blocker to the channel. We suggest that the volatile anesthetics produce
      conformational changes in these channels consistent with their ability to depress
      channel-mediated Ca2+ influx into myocytes.

PMID- 1986642
TI  - Acute tolerance in morphine analgesia: continuous infusion and single injection
      in rats.
AB  - This study aimed to determine whether the decline of the analgesic effect of
      morphine with a continuous infusion or that after a single injection correlates
      with the changes in brain concentration of morphine. The analgesic effect of
      morphine and its brain and serum concentrations were determined with a continuous
      8-h infusion at a constant rate and after a single subcutaneous injection of the
      agent. The analgesic effect was determined by measuring the threshold of motor
      response to noxious stimulation. Brain and serum concentrations of morphine were
      detected by radioimmunoassay with the use of 125I-labeled morphine. With the
      constant-rate (4 mg.kg-1.h-1, intravenous) morphine infusion, the peak of
      analgesia could not be maintained: the increase in the pain threshold at 2 h was
      1,003 g and at 8h was 286 g (a decrease in analgesia by 72%, P less than 0.0002).
      At the same time, the brain morphine concentration tended to increase, to 278
      ng/g at 2 h and 329 ng/g at 8 h. After the single morphine injection (6 mg/kg,
      subcutaneous), recovery from analgesia occurred at a much faster rate than did
      the decrease in morphine brain concentration; the decrease in pain threshold was
      79% at 90 vs. 30 min after the injection (P less than 0.0001), and the
      corresponding decrease in brain concentration was 28% (NS). The absence of
      correlation between analgesia and morphine brain concentration both with the
      constant-rate morphine infusion and after the single injection suggests the
      development of acute tolerance, which is pharmacodynamic in nature.

PMID- 1986643
TI  - Ejection fraction revisited.

PMID- 1986644
TI  - Lidocaine-induced spinal block can relieve central poststroke pain: role of the
      block in chronic pain diagnosis.

PMID- 1986645
TI  - Fatal massive air embolism during transurethral resection of the prostate.

PMID- 1986646
TI  - Intravenous calcitonin alleviates spinal anesthesia-induced phantom limb pain.

PMID- 1986647
TI  - Suspected venous air embolism during epidural anesthesia.

PMID- 1986648
TI  - Central anticholinergic syndrome following glycopyrrolate.

PMID- 1986649
TI  - Intraoperative subdural tension pneumocephalus arising after opening of the dura.

PMID- 1986650
TI  - Thrombocytopenia and cocaine abuse.

PMID- 1986651
TI  - Compatibility between Nellcor pulse oximeter probe and Puritan-Bennett surgical
      monitor.

PMID- 1986652
TI  - Another site for the pulse oximeter probe.

PMID- 1986653
TI  - Transdermal scopolamine and postoperative nausea and vomiting.

PMID- 1986654
TI  - Bronchospasm following revascularization of cadaver kidney graft.

PMID- 1986655
TI  - Delayed onset of pneumothorax following internal jugular vein cannulation.

PMID- 1986656
TI  - Hassle-free prevention of blood spillage during intravenous catheter placement.

PMID- 1986657
TI  - A modified Y-type set for efficient blood transfusion.

PMID- 1986658
TI  - Propofol and spontaneous movements: an EEG study.
AB  - Spontaneous movements during induction of anesthesia with propofol were studied
      in 21 children aged 6-12 yr. The children were randomly assigned to group A
      (propofol 3 mg.kg-1), B (propofol 5 mg.kg-1), or C (thiopental 5-7 mg.kg-1). A
      baseline electroencephalogram (EEG) was recorded during 10 min in children awake,
      supine with eyes closed and opened, and then from the beginning of induction
      until 5 min after tracheal intubation. Spontaneous movements were observed in all
      children in group A but only in 14% in groups B and C. The induction EEG
      sequences were similar for the three groups: after a mean latency of 12 s, the
      tracing showed an increase in frequency from 9 to 10 Hz (alpha waves) to more
      than 14 Hz (beta waves). This transition lasted approximately 2 s, followed by
      delta waves (2-3 Hz) that continued for 1-2 min. Finally, beta waves reappeared
      and progressively but incompletely replaced delta waves during the next 5 min.
      Neither spikes, spike-wave patterns, rhythmic theta waves, nor burst suppressions
      were observed. Spontaneous movements were recorded on videotape and analyzed
      after the completion of the study by a neurologist unaware of patient treatment.
      Videotape analysis of the periinduction period showed spontaneous movements to be
      dystonic and choreiform with flexion, twisting, or extension movements of all
      extremities. All movements occurred coincident with the appearance of delta waves
      on the EEG. Their dystonic nature and the absence of EEG abnormalities suggest a
      subcortical origin and argue against associated cortical epileptic activity.

PMID- 1986659
TI  - Double-blind comparison of oral transmucosal fentanyl citrate with oral
      meperidine, diazepam, and atropine as preanesthetic medication in children with
      congenital heart disease.
AB  - The effectiveness of oral transmucosal fentanyl citrate (OTFC) as preanesthetic
      medication was compared with oral meperidine, diazepam, and atropine (MDA) in 40
      pediatric patients scheduled to undergo repair of congenital heart defects. In a
      double-blinded manner, patients received a fentanyl lollipop (20-25
      micrograms/kg) and a placebo oral solution (0.4 ml/kg) (n = 20) or a placebo
      lollipop and an oral solution (0.4 ml/kg) of meperidine (1.5 mg/kg), diazepam
      (0.2 mg/kg), and atropine (0.02 mg/kg) (n = 20). The patient's vital signs,
      systolic and diastolic blood pressures, heart rate, respiratory rate, and
      oxyhemoglobin saturation (SpO2), as well as activity and apprehension scores were
      evaluated and recorded at baseline and at 10-min intervals. The patient's
      emotional status at the time of parental separation and at induction of
      anesthesia were also assessed. Side effects and onset of action were observed.
      After OTFC, onset of sedation was significantly faster than with the oral
      solution of meperidine, diazepam, and atropine. In both groups there was no
      significant change in heart rate. Although systolic blood pressure, diastolic
      blood pressure, and respiratory rate showed statistically significant decreases,
      these changes were not clinically significant. The child's emotional status at
      the time of separation from the parents and during induction was similar in both
      groups. Side effects with OTFC were more frequent: nose itching occurred in 65%,
      body itching in 10%, and vomiting in 30%. Two patients (10%) in the OTFC-treated
      group became hypoxemic (SpO2 less than 90) and required supplemental oxygen. In
      the group receiving oral meperidine, diazepam, and atropine, 10% had mild facial
      pruritus and 5% complained of a dry mouth.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1986660
TI  - Monitoring hepatic venous hemoglobin oxygen saturation in patients undergoing
      liver surgery.
AB  - Hepatic venous oxygen saturation (ShvO2) was continuously monitored in 33
      consecutive patients undergoing hepatic lobectomy. Fiberoptic pulmonary artery
      catheters were inserted into the hepatic vein (HV) and in the pulmonary artery
      through the right internal jugular vein before anesthetic induction. The success
      rate and mean time for HV catheterization were 100% and 14 min, respectively. The
      only complication of the procedure was nonsustained atrial or ventricular
      arrhythmias. Eighteen patients showed decreases in ShvO2 to less than 30% at skin
      incision, at temporary cessation of hepatic inflow, and/or at surgical
      manipulation of the liver. Clinical HV catheterization was easy to accomplish and
      may be a valuable technique in studying the extent and significance of hepatic
      ischemia during liver surgery.

PMID- 1986661
TI  - Coronary and left ventricular hemodynamic responses following reversal of
      flunitrazepam-induced sedation with flumazenil in patients with coronary artery
      disease.
AB  - The effects of reversal of flunitrazepam-induced sedation with flumazenil on
      coronary hemodynamics, myocardial oxygen consumption (MVO2), and left ventricular
      (LV) performance were investigated, in a double-blind trial, in 12 patients with
      stable coronary artery disease undergoing cardiac catheterization. Coronary sinus
      blood flow was measured by continuous thermodilution. Arterial and coronary sinus
      blood were analyzed for oxygen and lactate contents. The determinants of LV
      performance were obtained from the cardiac output measured by thermodilution and
      from left heart catheterization data. To reverse flunitrazepam-induced sedation,
      patients were randomly allocated to receive placebo or flumazenil (by increment,
      up to 1 mg) at the end of procedure. In the placebo group, no significant
      hemodynamic changes were observed. In the flumazenil group, heart rate, cardiac
      index, maximum velocity of shortening, and relaxation time constant were not
      significantly altered. By contrast, mean aortic pressure and LV end-diastolic
      pressure (baselines: 90 +/- 5 and 7.3 +/- 4.1 mmHg, respectively) increased (9%,
      P less than 0.05 and 67%, P less than 0.05, respectively) after flumazenil
      administration, but these changes represented mainly a return toward presedation
      values. MVO2 and coronary resistance were not significantly altered, whereas CSBF
      increased slightly (baseline: 119 +/- 20 ml/min; increase 10%, P less than 0.05).
      No electrocardiographic evidence of myocardial ischemia was observed during the
      study. These data show that reversal of benzodiazepine effects with flumazenil is
      not associated with a major alteration of LV systolic function, relaxation, or
      coronary hemodynamics in patients with coronary artery disease. Nevertheless, it
      should be cautiously used when LV end-diastolic pressure is increased at the time
      of its administration.

PMID- 1986662
TI  - Magnesium sulfate decreases maternal blood pressure but not uterine blood flow
      during epidural anesthesia in gravid ewes.
AB  - The purpose of this study was to determine whether administration of magnesium
      sulfate decreased maternal blood pressure during epidural anesthesia in gravid
      ewes. Twenty-two experiments were performed in 11 chronically instrumented
      animals between 0.8 and 0.9 of timed gestation. The experimental sequence
      included: 1) T = 0: magnesium sulfate 4 g intravenously over 5 min followed by an
      infusion of magnesium sulfate at 4 g/h, or normal saline iv followed by an
      infusion of normal saline alone; 2) T = 135 min: 500 ml normal saline
      intravenously over 12 min; and 3) T = 150 min: epidural administration of 2%
      lidocaine. The initial bolus of magnesium sulfate slightly decreased maternal
      mean arterial pressure (MAP) but increased uterine artery blood flow (UBF). The
      increase in UBF was accompanied by an increase in fetal PaO2 at 145 min in the
      magnesium sulfate group but not in the control group. At 165 min (i.e., 15 min
      after the epidural injection of lidocaine), epidural lidocaine resulted in a
      median sensory level of T-10 in the magnesium sulfate group and T-11 in the
      control group. During epidural anesthesia, maternal MAP was lower (P = 0.001) in
      the magnesium sulfate group than in the control group. At 165 min, maternal MAP
      was 18 +/- 3% below baseline (P = 0.0001) in the magnesium sulfate group but did
      not differ significantly from baseline in the control group. Maternal cardiac
      output and UBF did not differ from baseline after epidural injection of lidocaine
      in either group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1986663
TI  - Anesthetic effects on resting membrane potential are voltage-dependent and agent
      specific.
AB  - Membrane hyperpolarization (increase in resting potential) together with a
      conductance increase has been suggested as a common mechanism of anesthetic
      action. The current study compared the effects of halothane, enflurane, and
      isoflurane on resting membrane potential and conductance of hippocampal CA1
      neurons in vitro. At 1 MAC, halothane produced significant (P less than 0.01)
      hyperpolarization (-2.8 +/- 1.3 mV, mean +/- SD) accompanied by a conductance
      increase (6.2 +/- 2.7%). Enflurane also produced a significant (P less than
      0.001) hyperpolarization (-3.15 +/- 1.2 mV); however, this was accompanied by a
      conductance decrease (-4.5 +/- 1.5%). Isoflurane produced variable effects.
      Anesthetic-induced hyperpolarization was maximal in neurons with more negative
      initial resting potentials and was reduced by depolarization. Across agents,
      these relatively small changes in resting potential were not correlated with
      decreases in excitability as measured by synaptically evoked population spike
      depression. The results are not consistent with a common action of the three
      agents on a single ionic channel.

PMID- 1986664
TI  - Intraoperative estimation of cardiac output by transesophageal pulsed Doppler
      echocardiography.
AB  - To determine whether transesophageal echocardiography could be used to estimate
      intraoperative cardiac output, the authors studied 35 consecutive patients
      undergoing cardiovascular surgery (coronary artery disease [n = 22], aortic valve
      disease [n = 5], mitral valve stenosis [n = 5], peripheral vascular disease [n =
      3]). Two-dimensional echocardiographic and pulsed-wave Doppler signals of the
      pulmonary artery and mitral valve flow velocity were obtained simultaneously with
      thermodilution measurements of cardiac output. Cardiac output derived from pulsed
      Doppler imaging of pulmonary artery systolic flow velocity modestly correlated
      with the thermodilution-derived cardiac output (r = 0.65), but output determined
      from the mitral valve diastolic flow velocity did not (r = 0.24). Transesophageal
      echocardiography of pulmonary artery systolic flow satisfactorily detected
      intraoperative increases in cardiac output greater than 15% (sensitivity, 71%;
      specificity, 82%) but not decreases (sensitivity, 54%; specificity, 90%).
      Although this technique identifies increases in cardiac output greater than 15%,
      it does not detect decreases as accurately as those detected by thermodilution
      measurements. At this time, therefore, transesophageal Doppler echocardiography
      has significant limitations as an off-line monitor of cardiac output.

PMID- 1986665
TI  - Methotrexate: does it treat or induce asthma?

PMID- 1986666
TI  - Bronchial responsiveness is not increased by bronchoalveolar and bronchial lavage
      performed after allergen challenge.
AB  - Nonspecific bronchial responsiveness was studied in 23 allergic patients with a
      history of rhinitis and/or bronchial asthma who underwent fiberoptic bronchoscopy
      with bronchoalveolar and bronchial lavage (BAL-BL) 4h (Group A) or 24 h (Group B)
      after an allergen inhalation challenge. In all patients, the dose of methacholine
      causing an FEV1 fall of 15% (PD15) was determined at baseline, 24 h before
      allergen challenge. Methacholine bronchial challenge was repeated 1 h before BAL
      BL in patients of both groups and again 12 to 14 h after BAL-BL in Group A and 24
      h after BAL-BL in Group B. In patients of Group A, the values of methacholine
      PD15 after BAL-BL were not significantly different from those determined before
      BAL-BL. This was also the case in patients in whom bronchial responsiveness was
      increased after allergen challenge. In patients of Group B, methacholine PD15 was
      significantly decreased after allergen challenge, and this decrease was
      correlated with the occurrence and the severity of the late asthmatic reaction.
      Even in patients who showed dual asthmatic reactions and an increased
      responsiveness after allergen challenge, methacholine PD15 was not further
      decreased after BAL-BL. These data support the safety of a procedure combining
      bronchial allergen challenge with BAL-BL, which can be used for studies on the
      pathophysiology of bronchial asthma.

PMID- 1986667
TI  - The effect of inhaled corticosteroids on the maximal degree of airway narrowing
      to methacholine in asthmatic subjects.
AB  - Airway hyperresponsiveness in asthma is characterized by an increase in
      sensitivity and in maximal response to airway-narrowing stimuli. Long-term
      therapy with inhaled corticosteroids is known to reduce airway hypersensitivity
      in asthmatic patients. To investigate whether these drugs also reduce the maximal
      degree of airway narrowing we studied the effects of inhaled budesonide on the
      maximal response plateau of the dose-response curve to inhaled methacholine in
      mildly asthmatic patients in whom a raised plateau could be measured. Sixteen
      atopic patients with mild asthma were placed randomly into two parallel treatment
      groups to receive double-blindly either budesonide (400 micrograms twice daily)
      or placebo, inhaled via a Turbuhaler, for 4 wk. Before treatment, after 2 and 4
      wk of treatment, and after 2 and 4 wk of wash-out, complete dose-response curves
      to methacholine were obtained using a standardized 2-min tidal breathing method.
      The response was measured by FEV1, expressed in % fall from baseline. A plateau
      on the log dose-response curve was considered if three or more data points fell
      within a 5% response range. The maximal response was obtained by averaging the
      values on the plateau (MFEV1), and the sensitivity was calculated from the
      provocative concentration of methacholine, causing a 20% fall in FEV1 (PC20).
      After 4 wk of budesonide treatment, mean MFEV1 decreased from 41.6 to 33.7% fall
      (p = 0.0004). The changes in MFEV1 were significantly different between placebo
      and budesonide (p = 0.03). The geometric mean PC20 increased from 3.4 to 6.3
      mg/ml (p = 0.02), but the changes in PC20 were not different between the two
      groups (p = 0.23).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1986668
TI  - Thromboxane A2 biosynthesis in acute asthma and after antigen challenge.
AB  - Thromboxane A2 is a potent bronchial smooth muscle spasmogen in vitro, and it has
      been implicated in airway inflammation and in the genesis of bronchial
      hyperresponsiveness in asthma. We have examined the urinary excretion of a
      variety of products derived from thromboxane A2 (thromboxane B2, 2,3-dinor, and
      11-dehydro-thromboxane B2) and prostacyclin (6-oxo-PGF1 alpha and 2,3-dinor-6-oxo
      PGF1 alpha) using gas chromatography-mass spectrometry in patients admitted
      acutely to hospital with severe asthma and in atopic volunteers after bronchial
      antigen challenge. Urinary excretion of all thromboxane-derived products was
      markedly increased in a number of patients with severe acute asthma compared with
      that in a nonsmoking control population, in some cases approaching those
      previously described in myocardial infarction: TXB2, 31.6 +/- 12.0 versus 6.5 +/-
      0.9; 2,3-dinor-TXB2, 79.0 +/- 19.2 versus 29.5 +/- 2.7; and 11-dehydro-TXB2,
      234.3 +/- 65.3 versus 25.0 +/- 2.1 ng/mmol creatinine (p less than 0.001).
      Urinary prostacyclin-derived products were also significantly raised in acute
      asthma. In contrast, after inhaled allergen challenge in atopic volunteers, which
      caused significant bronchoconstriction, urinary excretion of thromboxane-derived
      products was not significantly elevated: TXB2, 5.6 +/- 1.1 versus 5.7 +/- 1.0;
      2,3-dinor-TXB2, 41.2 +/- 12.5 versus 28.5 +/- 6.9; and 11-dehydro-TXB2, 69.8 +/-
      17.6 versus 39.7 +/- 11.2 ng/mmol creatinine. In a separate experiment, less than
      2% of exogenously administered TXB2 to the airway appeared as urinary thromboxane
      derived products, suggesting that production of greater than or equal to 1
      microgram of TXA2 in vivo would be required to increase urinary thromboxane
      excretion twofold.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1986669
TI  - Morphometry of the airways during late responses to antigen challenge in the rat.
AB  - To quantitate the structural changes in the airways that contribute to the late
      bronchial response (LR) to antigen challenge we killed six Brown-Norway rats,
      sensitized to ovalbumin (OA) and challenged by aerosol, during the LR and
      compared the dimensions of the intraparenchymal airways with those of six control
      animals. Lungs were rapidly frozen with liquid nitrogen and fixed in Carnoy's
      solution. Paraffin sections were stained with hematoxylin-phloxine-saffron. At
      the time of the LR (382 +/- 39 min after OA challenge), RL increased from the
      baseline value (0.067 +/- 0.034 cm H2O.ml-1.s) by 0.107 +/- 0.03 cm H2O.ml-1.s (p
      less than 0.05). RL did not change significantly in the control rats. The lumen
      size and the wall area of all membranous airways were measured and were corrected
      for airway size by dividing by the basement membrane length squared (BM2). There
      was no increase in airway wall area in OA-challenged animals. However, the lumen
      of large airways (BM: 2.0 to 2.99 mm) was significantly less for the OA
      challenged animals (0.039 +/- 0.0055 mm2) than for the control animals (0.058 +/-
      0.0063 mm2; p less than 0.05). In six additional rats, the distribution of mast
      cells (MC) in the bronchial tree was determined. Tissues were fixed with Carnoy's
      solution and stained with a modified May-Grunwald-Giemsa stain. There were
      significantly more MC in the large airways than in medial or small airways. We
      conclude that smooth muscle constriction of large airways and not airway wall
      edema accounts for the LR in the rat. The distribution of the mast cells
      corresponds closely to the site of bronchoconstriction.

PMID- 1986670
TI  - Quantitative structural analysis of peripheral airways and arteries in sudden
      fatal asthma.
AB  - The peripheral airways and the adjacent muscular pulmonary arteries were studied
      by morphometric methods in the autopsy lungs of six asthmatic subjects who died
      suddenly during an asthma attack, and they were compared with those of six
      control subjects who died of other causes and had no history of respiratory
      diseases. Bronchioles of asthmatic subjects had an increased amount of lumen
      occlusion (p less than 0.01), smooth muscle thickness (p less than 0.001), and
      inflammatory infiltrate (p less than 0.001), and both mononuclear cells and
      eosinophils contributed to this increased inflammation. The muscular pulmonary
      arteries adjacent to occluded and inflamed bronchioles did not have the
      morphologic features of chronic hypoxia, as shown by the normal medial and
      intimal thickness, but they had an important inflammatory process in their walls
      that was particularly marked at sites adjacent to airways. Although the
      functional significance of these findings is unknown, they may be responsible in
      part for the gas exchange abnormalities observed in acute severe asthma.

PMID- 1986671
TI  - Bronchiolar inflammation and fibrosis associated with smoking. A morphologic
      cross-sectional population analysis.
AB  - The lungs of 42 smokers and 13 nonsmoking males of various ages who died suddenly
      and unexpectedly were examined grossly using Gough-Wentworth whole-lung sections
      and by microscopic planimetry to assess the severity and prevalence of emphysema.
      The bronchioles in representative histologic sections were evaluated for
      inflammation and epithelial metaplasia as well as for fibrosis and muscular
      hypertrophy. Postmortem interviews with next of kin established a history of
      cigarette smoking and excluded possible occupational exposures to toxic or
      particulate inhalants. Emphysematous changes were not prominent in members of the
      study group, but they tended to be more severe in smokers (p = 0.059) and
      increased in severity with age (p less than 0.001). Inflammatory changes (so
      called smoker's bronchiolitis) were evident in smokers of all ages, although they
      were significantly less prominent in the lungs of older smokers. On the other
      hand, respiratory and membranous bronchiolar wall fibrosis was increasingly
      evident in older smokers (p less than 0.05). Muscular hypertrophy in the
      bronchiolar walls was significantly greater in smokers, but a change with age was
      not observed. These findings strongly suggest that bronchiolar fibrosis is
      associated with chronic cigarette use. These lesions occur independently of
      emphysema and may account for some of the subtle physiologic alterations observed
      in smokers.

PMID- 1986672
TI  - A positron emission tomographic comparison of pulmonary vascular permeability
      during the adult respiratory distress syndrome and pneumonia.
AB  - We measured extravascular density (EVD) and the pulmonary transcapillary escape
      rate (PTCER) for 68Ga-transferrin using positron emission tomography in 14 normal
      volunteers and 29 patients with radiographic infiltrates, including six patients
      with congestive heart failure (CHF), eight patients with the adult respiratory
      distress syndrome (ARDS), and 15 patients with focal pneumonia. Contralateral,
      radiographically normal regions were also evaluated in the patients with focal
      pneumonia. Mean EVD was elevated in the patients with CHF, ARDS, and pneumonia in
      regions of radiographic infiltrate compared with values from normal subjects (p
      less than 0.05), but it was not significantly different among the three patient
      groups. PTCER in normal subjects and in patients with CHF was not significantly
      different (21 +/- 11 versus 44 +/- 16 x 10(-4) min-1, respectively, p = NS).
      PTCER was elevated in regions of infiltrate because of either pneumonia (173 +/-
      99) or ARDS (170 +/- 79). PTCER was also elevated in regions contralateral to
      those with focal infiltrate during pneumonia, even though these regions were
      radiographically normal and had normal EVD values. These results suggest that
      PTCER is a sensitive but nonspecific index of abnormal pulmonary vascular
      permeability, which may be useful for classifying patients in clinical studies of
      pulmonary edema.

PMID- 1986673
TI  - Morphometry of the subepithelial circulation in sheep airways. Effect of vascular
      congestion.
AB  - In order to quantitate the subepithelial microvascular volume and its relation to
      the airway lumen, we conducted a morphometric analysis of the vascular
      compartment in the wall of the trachea (within a 55-microns depth from the
      epithelial basement membrane) and of 1.0 and 0.5-mm bronchioles of sheep. The
      lungs were fixed by bronchial and pulmonary artery perfusion with glutaraldehyde
      under three experimental conditions: (1) bronchial artery pressure, 100 mm Hg
      pulmonary artery pressure, 20 mm Hg (control); (2) bronchial artery pressure, 100
      mm Hg, pulmonary artery pressure, 40 mm Hg (pulmonary hypertension, PH); (3)
      bronchial artery pressure, 100 mm Hg, pulmonary artery pressure, 40 mm Hg
      (pharmacologic vasodilation with sodium nitroprusside, PH + V). Venous pressures
      were atmospheric. Under control conditions, the microvascular volume fraction
      comprised 12, 16, and 15% of the subepithelial tissue in the trachea and 1-mm and
      0.5-mm bronchioles, respectively. PH increased the microvascular volume fraction
      in the bronchioles (p less than 0.05), but it had no effect on the
      microvasculature in the trachea. PH + V approximately doubled the microvascular
      volume fraction in the trachea and the bronchioles. PH increased the mean wall
      thickness, and PH and PH + V decreased the airway cross-sectional area in the 1
      mm bronchioles. These observations demonstrate that the microvasculature
      constitutes a considerable volume fraction of the subepithelial airway tissue and
      that vascular congestion can narrow the bronchiolar lumen.

PMID- 1986674
TI  - Sweet's syndrome with lung involvement.
AB  - Severe dyspnea and pulmonary infiltrates were associated with recurrent episodes
      of Sweet's syndrome (acute febrile neutrophilic dermatosis) in a 54-yr-old woman
      with myelodysplasia. Lung and skin biopsies revealed a sterile infiltration of
      the interstitial tissues by mature neutrophils. Corticosteroid therapy resulted
      in rapid clinical improvement; however, recurrent episodes were increasingly
      resistant to therapy, and she ultimately died from respiratory failure. Sweet's
      syndrome involving the lung is rare, with only two previously reported cases
      documented by lung biopsy. Prompt recognition of Sweet's syndrome with lung
      involvement is important because of the potential for severe respiratory
      compromise.

PMID- 1986675
TI  - Methotrexate-induced asthma.
AB  - A patient with rheumatoid arthritis developed pulmonary symptoms and function
      test abnormalities consistent with asthma during methotrexate therapy.
      Assessments of airway responsiveness to methacholine during therapy revealed
      airway hyperreactivity that reverted to normal when the methotrexate was stopped.
      An extension of the methotrexate dosage interval from 7 to 10 days resulted in an
      abolition of the asthma, which remained in remission despite a return to a weekly
      cycle after a 3-month period of 10-day cycles.

PMID- 1986676
TI  - Prognosis of idiopathic pulmonary fibrosis in patients with mucous
      hypersecretion.
AB  - In order to determine the prognosis of patients with chronic idiopathic pulmonary
      fibrosis (IPF), we evaluated clinical, laboratory, and bronchoalveolar lavage
      (BAL) data at the onset of IPF in 25 patients who survived beyond 1 yr (nine
      women and 16 men, 59 +/- 3 yr of age, mean +/- SE). When the patients were
      divided into two groups according to whether they had or did not have mucous
      hypersecretion, 11 patients with hypersecretion (Group A) had a poorer survival
      rate (6 yr) than did 14 patients without hypersecretion (Group B) (10 yr) (p less
      than 0.01). Further, there was a significant negative correlation between sputum
      volume and the duration of survival in 25 patients (r = -0.55, p less than 0.01).
      Before glucocorticoid treatment, we also found significantly larger numbers of
      neutrophils (17%) and eosinophils (5%) in differential cell counts of
      bronchoalveolar lavage fluid (BALF) in Group A than in Group B (neutrophils, 1%;
      eosinophils, 0.6%) (p less than 0.05 each). Chest radiographic findings and other
      laboratory data including pulmonary function tests did not correlate with the
      survival rate. These findings suggest that mucous hypersecretion as well as
      neutrophils and eosinophils in BALF are among the determinants of prognosis in
      patients with chronic IPF.

PMID- 1986677
TI  - The influence of human immunodeficiency virus infection on tuberculosis in
      Kampala, Uganda.
AB  - The clinical, radiographic, and microbiologic features of 59 patients with
      pulmonary tuberculosis in Kampala, Uganda were studied and correlated with the
      serologic reactivity to the human immunodeficiency virus (HIV) of these patients.
      Two-thirds of the patients with tuberculosis were HIV-seropositive. Histories of
      fever and weight loss were more prominent in HIV-seropositive patients, and
      perihilar and basilar infiltrative diseases were more frequently seen in HIV
      seropositive patients. Although all patients responded similarly to drug therapy,
      cutaneous drug reactions were seen in nearly one-third of HIV-seropositive
      patients receiving thiacetazone.

PMID- 1986678
TI  - Effects of positive end-expiratory pressure on the gradient for venous return.
AB  - The major mechanism whereby positive end-expiratory pressure (PEEP) decreases
      cardiac output is believed to be a decrease in the pressure gradient for venous
      return. However, although PEEP increases right atrial pressure (PRA), It may also
      elevate mean systemic pressure (PMS), the static circulatory filling pressure
      that is the upstream pressure for venous return. In an intact canine preparation,
      we studied the effects of 15 cm H2O PEEP on cardiac output, PRA, and PMS (the
      equilibrium PRA during ventricular fibrillation). To examine the role of
      neurovascular reflexes, PEEP was applied before and after either carotid sinus
      and vagal denervation (CSV) or total spinal anesthesia with arterial pressure
      restored by epinephrine infusion (SAE). To examine the effects of PEEP-induced
      elevations of abdominal pressure, the abdomen was bound or widely opened and the
      abdominal contents exteriorized. With reflexes intact, neither binding nor
      opening the abdomen altered the rise in PMS during PEEP. CSV attenuated the rise
      in Pms by 17% (Control, 4.89 +/- 0.3 SE; CSV, 4.04 +/- 0.22 mmHg; p less than
      0.01), and SAE attenuated it by 49% (Control, 4.21 +/- 0.27; SAE, 2.14 +/- 0.31
      mmHg; p less than 0.00005). After either CSV or SAE, the rise in Pms was not
      affected by binding. PEEP decreased (Pms-PRA) only when the abdomen was bound
      because of a greater rise in PRA, or during SAE because of a lesser rise in Pms.
      Under control conditions, PEEP increased Pms and PRA equally [(PRA-Pms) = 3.89 +/
      0.26 without PEEP versus 4.13 +/- 0.29 mm Hg with PEEP]. We conclude that PEEP
      increases Pms by both reflex and mechanical means independent of increased
      abdominal pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1986679
TI  - Body mass index and neck circumference in obstructive sleep apnea.

PMID- 1986680
TI  - Estimating left ventricular filling pressure during positive end-expiratory
      pressure in humans.
AB  - In the critically ill, accurate measurements of left ventricular (LV) filling
      pressure using pulmonary artery occlusion pressure (Ppao) are important for
      diagnostic and therapeutic purposes. In patients receiving positive end
      expiratory pressure (PEEP), Ppao may not reflect LV filling pressure because of
      elevated pericardial pressure (Ppc). It has been proposed that in humans, Ppc and
      right atrial pressure (PRA) are equal, so that referencing Ppao to PRA may
      improve the assessment of LV filling pressure when Ppc is elevated. Similarly, it
      has also been shown in the dog that nadir Ppao immediately after airway
      disconnection from PEEP (nadir Ppao), accurately reflects LV filling pressure
      when LV filling pressure is greater than or equal to 10 mm Hg. We examined
      methods of estimating LV filling pressure using Ppao measurements under
      conditions in which increases in Ppc were the primary determinants of differences
      in the two measurements. Using left atrial pressure (PLA) relative to Ppc, called
      transmural PLA (PLAtm), as LV filling pressure, we compared the accuracy of Ppao,
      nadir Ppao, and Ppao relative to PRA to reflect PLAtm in 15 postoperative cardiac
      surgery patients in whom an air-filled pericardial balloon catheter and a left
      atrial catheter were inserted during surgery. PEEP was sequentially increased
      from zero to 15 cm H2O. We found that PRA always exceeded Ppc (p less than 0.01)
      and increased less with PEEP than did Ppc (p less than 0.05). At less than or
      equal to 5 cm H2O PEEP, both Ppao and nadir Ppao were similar to each other and
      to PLAtm.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1986681
TI  - Endothelium-derived relaxing factor inhibits hypoxic pulmonary vasoconstriction
      in rats.
AB  - The hypothesis that endothelium-derived relaxing factor (EDRF) modulates hypoxic
      pulmonary vasoconstriction (HPV) was tested in isolated, blood-perfused rat lungs
      ventilated with gas mixtures of 21% O2-5% CO2-74% N2 (normoxia) or of 3% O2-5%
      CO2-92% N2 (hypoxia); 30 microM NG-monomethyl-L-arginine (L-NMMA), an inhibitor
      of EDRF production, caused a reduction in the endothelium-dependent relaxant
      response to acetylcholine (ACh) from 62 +/- 7, 88 +/- 4, and 100 +/- 4% to 26 +/-
      8, 49 +/- 12, and 75 +/- 7% at ACh concentrations of 1, 10, and 100 microM,
      respectively (p less than 0.05 at all concentrations), indicating that L-NMMA
      acts via the inhibition of EDRF production. L-NMMA induced a concentration
      related augmentation in HPV of 20 +/- 5, 32 +/- 8, and 34 +/- 8% at
      concentrations of 30, 300, and 1,000 microM (p less than 0.05, compared with a
      vehicle control group at all concentrations). The pressor response to a dose of
      angiotensin II (A-II), which produced the same increase in pulmonary artery
      pressure as that induced by hypoxia, was also significantly augmented (2 +/-
      0.6%), but to a lesser extent. The augmentation of HPV by 30 microM L-NMMA was
      completely reversed by 1 mM L-arginine (a precursor of EDRF), but not by D
      arginine (an isomer of L-arginine). One and 6 mM L-arginine, but not 6 mM D
      arginine caused a significant inhibition of HPV by 20 +/- 2 and 47 +/- 12% (p
      less than 0.05, compared with the vehicle control group) and a small but not
      significant reduction in A-II-mediated contraction.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1986682
TI  - Developmental changes in pleural liquid protein concentration in sheep.
AB  - The source of normal pleural liquid is thought to be the systemic circulation of
      the pleural membranes rather than the pulmonary circulation of the nearby lung.
      Evidence for a systemic origin comes from the low protein concentration of
      pleural liquid in adult sheep, which is consistent with protein sieving from a
      high-pressure circulation. During normal development from fetal to adult life,
      systemic vascular pressure increases. We therefore reasoned that if pleural
      liquid comes from the systemic circulation, pleural liquid protein concentration
      relative to plasma protein concentration should decrease during normal
      development. To test this hypothesis we did thoracotomies on 14 fetal, 9 newborn,
      and 15 adult sheep and collected pleural liquid and plasma for measurement of
      total protein and albumin concentrations. In separate experiments we measured
      steady-state systemic and pulmonary vascular pressures in age-matched chronically
      instrumented fetal, newborn, and adult sheep. The protein concentration in
      pleural liquid relative to that in plasma (pleural liquid/plasma) decreased
      progressively with age (fetuses, 0.50 +/- 0.15 [SD]; newborns, 0.27 +/- 0.08;
      adult, 0.15 +/- 0.05); the trend was similar for pleural liquid/plasma albumin
      ratios as a function of age. Systemic arterial pressure increased progressively
      during development, whereas pulmonary arterial pressure decreased from the fetus
      to the adult sheep. These observations support the hypothesis that normal pleural
      liquid originates from a systemic circulation.

PMID- 1986683
TI  - Serum and lavage lactate dehydrogenase isoenzymes in pulmonary alveolar
      proteinosis.
AB  - Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by the
      accumulation of lipoproteinaceous material in the alveolar space. Serum lactate
      dehydrogenase (LDH) has been noted to be elevated in patients with PAP in
      previous studies. We sought to extend this observation in a series of patients
      with PAP by looking at total serum LDH concentrations and LDH isoenzyme fractions
      measured before and after whole lung lavage. Total LDH and LDH isoenzymes were
      also determined in the lavage effluent. Total serum LDH was elevated before
      lavage in 10 of 16 patients. Prelavage serum LDH and prelavage alveolar-arterial
      O2 gradient showed a significant correlation (r = 0.62, p less than 0.05). A
      decrease in serum LDH was found after lavage in all patients in whom postlavage
      data was available (paired t test, p less than 0.01, n = 11), although the
      magnitude of this decrease varied considerably. The isoenzyme pattern before
      lavage was isomorphic, and this pattern was unchanged after whole lung lavage.
      This was in marked contrast to the LDH isoenzyme pattern observed in the lavage
      effluent, which showed a lower percent LDH1 and LDH2 and a higher percent LDH3,
      LDH4, and LDH5 when compared with the corresponding prelavage isoenzyme
      percentages for serum (unpaired t test, p less than 0.001). There was no
      correlation between the total serum LDH concentration and the total lavage LDH
      concentration. These data confirm that elevated serum LDH is a common finding in
      PAP. Furthermore, the LDH elevation found consistently in the alveolar fluid
      points to this as the source of the serum LDH.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1986684
TI  - Comparison of lung alveolar and tissue cells in silica-induced inflammation.
AB  - The silicon dioxide mineral, cristobalite (CRS) induces inflammation involving
      both alveolar cells and connective tissue compartments. In this study, we
      compared lung cells recovered by whole lung lavage and by digestion of lung
      tissue from rats at varying times after 8 days of exposure to aerosolized CRS.
      Control and exposed rats were examined between 2 and 36 wk after exposure.
      Lavaged cells were obtained by bronchoalveolar lavage with phosphate-buffered
      saline. Lung wall cells were prepared via collagenase digestion of lung tissue
      slices. Cells from lavage and lung wall were separated by Percoll density
      centrifugation. The three upper fractions, containing mostly macrophages, were
      cultured, and the conditioned medium was assayed for effect on lung fibroblast
      growth and for activity of the lysosomal enzyme, N-acetyl-beta-D-glucosaminidase.
      Results demonstrated that the cells separated from the lung walls exhibited
      different reaction patterns compared with those cells recovered by lavage. The
      lung wall cells exhibited a progressive increase in the number of macrophages and
      lymphocytes compared with a steady state in cells of the lung lavage. This
      increase in macrophages apparently was due to low density cells, which showed
      features of silica exposure. Secretion of a fibroblast-stimulating factor was
      consistently high by lung wall macrophages, whereas lung lavage macrophages
      showed inconsistent variations. The secretion of NAG was increased in lung lavage
      macrophages, but decreased at most observation times in lung wall macrophages. No
      differences were found among cells in the different density fractions regarding
      fibroblast stimulation and enzyme secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1986685
TI  - A sensitive double-sandwich ELISA for neutrophil elastase. Assay results in
      unconcentrated bronchoalveolar lavage fluid.
AB  - We developed a sensitive double-sandwich ELISA assay for neutrophil elastase (NE)
      using affinity-purified NE antibody. The assay was capable of detecting NE levels
      of 0.2 ng/ml and was used to determine NE in bronchoalveolar lavages (BAL) of 12
      healthy subjects (6 nonsmokers and 6 smokers) with a mean age of about 27 yr. NE
      levels in the unconcentrated cell-free supernatant of BAL, subjected to high
      speed centrifugation (17,000 x g for 30 min) to sediment subcellular debris, were
      similar in the smokers who abstained overnight from smoking and in the nonsmokers
      (24.4 +/- 13.9 versus 23.7 +/- 12.3 ng/mg [SD] albumin). NE levels were
      significantly higher in lavage fluid not subjected to high-speed centrifugation,
      reflecting the presence of NE bound to subcellular debris that was sedimented by
      high-speed centrifugation. Concentration by ultrafiltration through a Millipore
      CX-10 filter was accompanied by loss of protein with a relatively greater loss of
      NE than albumin, resulting in lower NE/albumin ratios in concentrated than in
      unconcentrated lavage. It is therefore recommended that NE levels be determined
      on unconcentrated BAL after high-speed centrifugation to sediment subcellular
      debris.

PMID- 1986686
TI  - Prevalence of Mycobacterium avium complex in respiratory specimens from AIDS and
      non-AIDS patients in a San Francisco hospital.
AB  - Over the past several years there has been a large increase in the recovery of
      Mycobacterium avium complex (MAC) isolates from respiratory specimens submitted
      to the clinical laboratory at San Francisco General Hospital (SFGH). This
      increase in MAC recovery correlates with an increase in the number of cases of
      acquired immunodeficiency syndrome (AIDS) in the community. Although it is well
      known that MAC is often isolated from patients with AIDS, the isolation of MAC
      from respiratory specimens is often attributed to contamination of the specimen
      with MAC organisms present in the environment. To determine whether the increase
      in MAC isolates recovered at SFGH was due to an increase in environmental
      contamination of specimens or to the increase in our AIDS patient population, we
      conducted a study of the prevalence of MAC in respiratory specimens from AIDS
      versus non-AIDS patients. Results of specimens submitted to the clinical
      laboratory at SFGH for culture of mycobacteria were reviewed over a 12-yr period,
      from 1977 through 1988. The prevalence of MAC in respiratory specimens from AIDS
      and non-AIDS patients was determined for 4 yr during this period: the pre-AIDS
      year 1977; the first year AIDS was reported in San Francisco, 1981; 1984; and
      1987. In 1977 and 1981 the prevalence of MAC in respiratory specimens was less
      than or equal to 0.5%, and all MAC isolates were recovered from non-AIDS
      patients. In 1984 the prevalence of MAC in respiratory specimens for AIDS and non
      AIDS patients was 6.5 and 0.3%, respectively, and in 1987, 8.8 and 0.3%,
      respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1986687
TI  - Lung health consequences of reported accidental chlorine gas exposures among
      pulpmill workers.
AB  - The long-term consequences of accidental chlorine gas exposure have been
      investigated, mainly in the community setting, among persons exposed as a result
      of a nearby chlorine spill. This circumstance is not analogous to the more
      frequent chlorine or chlorine dioxide gas overexposures that occur commonly in
      pulpmills over a background of a low level of gas exposure. To investigate the
      respiratory health consequences of these accidental exposures ("chlorine
      gassing") in the industrial setting, we carried out a cross-sectional respiratory
      health survey among workers at a British Columbia coastal pulpmill and a nearby
      rail maintenance yard. A greater proportion of pulpmill workers were unavailable
      for study because of illness (10.5% versus 2.4% in the railyard, p less than
      0.01). Procedures involved simple spirometry, respiratory symptom assessment, and
      measurement of average levels of air contaminants. Average chlorine levels in the
      pulpmill were below 1 ppm; however, 60% of the pulpmill workers reported one or
      more accidental "chlorine gassing" incidents. Pulpmill workers who reported being
      "gassed" were significantly more likely to report wheezing on occasion than were
      other pulpmill workers and railyard workers (rate for these three groups:
      nonsmokers: 8, 2, 1%; ex-smokers: 17, 11, 7%; current smokers: 42, 21, 19%; p
      less than 0.05). No significant lung function differences were found between the
      overall pulpmill group and the railyard workers; however, nonsmoking and formerly
      smoking pulpmill workers who reported being "gassed" had significantly lower
      average midmaximal flow rate and FEV1/FVC ratio than did their counterparts in
      the remainder of the pulpmill population (p less than 0.05).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1986688
TI  - Silicosis, chronic airflow limitation, and chronic bronchitis in South African
      gold miners.
AB  - In a cross-sectional study of a working population of black South African gold
      miners, 1,197 men were studied with respiratory and occupational questionnaires,
      lung function tests, and chest radiographs. The study was designed to examine the
      effects of silicosis on respiratory symptoms and lung function. A total of 857
      men with chronic, simple silicosis and 340 men without silicosis were included in
      the sample. Other determinants of lung disease including the duration and
      intensity of underground dust exposure and tobacco smoking were also examined.
      Three distinct pulmonary disorders could be discerned: silicosis-associated
      pulmonary dysfunction with dyspnea on effort; chronic airflow limitation, which
      was related to the duration of underground exposure; and a chronic bronchitic
      symptom complex, which reflected the intensity of dust exposure in the workplace.
      Chronic, uncomplicated silicosis was found to be associated with significant loss
      of lung function, and all of the measured indices, FVC, FEV1, FEV1/FVC%, maximal
      midexpiratory flow rate (MMEF), and lung diffusion for carbon monoxide measured
      by the single-breath method (DLCO) were reduced. When comparing men with Category
      3/3 nodule profusion with men without silicosis, reductions of FVC of 351 ml,
      FEV1 of 447 ml, MMEF of 1.04 L/s, and DLCO of 4.7 ml/min/mm Hg (p = 0.0001) were
      detected after controlling for age, height, the direct effects of the underground
      environment, and tobacco smoking. Dyspnea on effort was more common in the men
      with silicosis (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1986689
TI  - Reductions in exercise lactic acidosis and ventilation as a result of exercise
      training in patients with obstructive lung disease.
AB  - Though exercise training is part of most pulmonary rehabilitation programs,
      whether there is a physiologic basis for increased exercise tolerance is unclear.
      We sought to determine whether patients with chronic obstructive pulmonary
      disease (COPD) are capable of obtaining a physiologic training effect, as
      manifested by a reduction in blood lactate and ventilation (VE) at a given level
      of exercise. We also sought to determine whether training work rate determines
      the size of the training effect. Nineteen participants with COPD of predominantly
      moderate severity in an inpatient rehabilitation program performed two cycle
      ergometer exercise tests at a low and a high work rate for 15 min or to tolerance
      and also an incremental exercise test to tolerance. Arterial blood was sampled
      for blood gas and lactate analyses. Identical tests were performed before and
      after 5-day-per-week cycle ergometer training for 8 wk either for 45 min/day at a
      high work rate (average, 71 W) or for a proportionally longer time at a low work
      rate (average, 30 W). Average FEV1 was 56 +/- 12% predicted and did not change
      with training. Peak exercise lactate (average, 6.5 mEq/L) was not correlated with
      FEV1. For the high work rate training group, identical work rates engendered less
      lactate (4.5 versus 7.2 mEq/L) and less VE (48 versus 55 L/min) after training;
      the low work rate training group had significantly less lactate and VE decrease
      (p less than 0.01). Further, endurance time for the high constant work rate
      increased 73% in the high work rate training group but only 9% in the low work
      rate training group. At identical work rates, VE decrease average 2.5 L/min per
      mEq/L decrease in lactate (r = 0.75). We conclude that most COPD subjects studied
      increased blood lactate at low work rates. Many of these patients were able to
      achieve a physiologic training effect. Though total work was the same, training
      at a high work rate was more effective than was training at a low work rate. The
      lower VE requirement to perform exercise was in proportion to the lower lactate
      level, but the VE decrease for a given decrease in lactate was smaller than that
      seen in normal subjects (7.2 L/min/mEq/L), apparently because patients with COPD
      fall to hyperventilate in response to lactic acidosis (PaCO2 does not drop).
      These findings provide a physiologic rationale for exercise training of patients
      with COPD.

PMID- 1986690
TI  - Snoring and sleep architecture.
AB  - The purpose of this study was to examine whether snoring adversely affects sleep
      architecture and sleep efficiency, and thus may account for the frequent
      complaints of daytime tiredness and fatigue expressed by heavy snorers. We
      recruited eight self-confessed heavy snorers and six self-confessed nonsnorers.
      All subjects had full nocturnal polysomnography, including continuous monitoring
      of snoring, which was quantified by counting the number of snores per hour of
      sleep (snoring index), the number of snores per minute of snoring time (snoring
      frequency), maximal and mean nocturnal sound intensity (dBmax and dBmean,
      respectively). We found that even the self-confessed nonsnorers snored lightly,
      with significantly smaller frequency and index than the heavy snorers. Sleep
      architecture was similar in both groups. Distribution of snoring among the sleep
      stages differed for light and heavy snorers: light snorers snored uniformly
      throughout all sleep stages, whereas heavy snorers tended to snore more during
      slow-wave and REM sleep. Snoring frequency and snoring index were similar during
      all sleep stages in light snorers, but they were higher during slow-wave sleep in
      heavy snorers. Wakefulness time after sleep onset and sleep efficiency correlated
      significantly with the snoring index. We conclude that although snoring does not
      affect sleep architecture in general, it influences sleep efficiency and
      wakefulness time after sleep onset; this may have an adverse effect on daytime
      function of heavy snorers.

PMID- 1986691
TI  - Inspiratory muscle performance and pulmonary function changes in insulin
      dependent diabetes mellitus.
AB  - The study examined pulmonary function parameters of 36 patients with insulin
      dependent diabetes mellitus and analyzed their inspiratory muscle performance.
      The control group consisted of 40 healthy reference persons of a sex ratio, age,
      height, and weight distribution similar to those of the patients. The pulmonary
      function test included the measurement of the lung volumes and the maximal
      expiratory flow-volume curves. The values of maximal sniff esophageal (Pes) and
      transdiaphragmatic pressures (Pdi) were used as parameters for global inspiratory
      muscle strength and diaphragm strength, respectively. The 12-s maximum voluntary
      ventilation (MVV) test supplied the parameter of inspiratory muscle endurance.
      The diabetic patients showed a highly significant decreased value for their
      inspiratory vital capacity (VCin) compared with that of the control subjects
      (4.75 +/- 0.84 versus 5.36 +/- 1.37 L; p less than 0.01). Inspiratory muscle
      performance in the diabetic patients was also restricted. Sniff Pes was
      significantly lower in the diabetic group (p less than 0.05); sniff Pdi (p less
      than 0.01) and MVV (p less than 0.05) were also low. The results did not
      correlate with either the duration of diabetes or the quality of metabolic
      control measured by glycosylated hemoglobin concentration. The reduction of VCin
      in diabetic patients may have been caused partly by the reduced capacity of the
      inspiratory muscles.

PMID- 1986693
TI  - Persistent necrotic digits in a patient with the acquired immunodeficiency
      syndrome. Herpes simplex virus infection.

PMID- 1986692
TI  - Callused feet, thick nails, and white tongue. Pachyonychia congenita.

PMID- 1986694
TI  - Tender linear lesions of the fingers. Acrokeratoelastoidosis (acquired type) or
      degenerative collagenous plaques of the hands.

PMID- 1986696
TI  - Advantages of electrocautery.

PMID- 1986695
TI  - Purpura and recurrent ulcers on the lower extremities. Essential
      cryofibrinogenemia.

PMID- 1986697
TI  - Jackson's 'remarkable case of xanthelasma'.

PMID- 1986698
TI  - Angiopathic pathogenesis of clinical manifestations in prolidase deficiency.

PMID- 1986699
TI  - Pruritic urticarial plaques and papules of pregnancy and skin distention.

PMID- 1986700
TI  - The pinnal hair sign.

PMID- 1986701
TI  - A peculiar case of linear IgA bullous dermatosis.

PMID- 1986702
TI  - Eruptive capillary hemangiomas.

PMID- 1986703
TI  - Acquired bromhidrosis in an 8-year-old boy secondary to a nasal foreign body.

PMID- 1986704
TI  - No effect of topical tretinoin on lentigo maligna.

PMID- 1986705
TI  - Topically administered fluorouracil in acrodermatitis continua of Hallopeau.

PMID- 1986706
TI  - The word is out.

PMID- 1986707
TI  - Intraepithelial anchoring fibril components.
AB  - Cultured human keratinocytes and cultured human cervical carcinoma cells (ME-180)
      contained intracellular pools of antigens that reacted with the anchoring fibril
      antibodies AF1 and AF2. In keratinocytes, these antigens formed a basement
      membrane-like structure near the apical portions of the cells. Using flow
      cytometric techniques, pretreatment of the ME-180 cells with acetone revealed
      large intracellular pools of antigen. The intracellular epitope was calcium
      sensitive. Some forms of recessive dystrophic epidermolysis bullosa have
      retention of intracellular portions of the anchoring fibril suggesting a relation
      of the intracellular anchoring fibril antigens to that disease.

PMID- 1986708
TI  - Ultrastructural localization of calcium in psoriatic and normal human epidermis.
AB  - With ion capture cytochemistry, we previously demonstrated the distribution of
      calcium ions in murine epidermis, a pattern consistent with a role for this ion
      in the regulation of epidermal differentiation. Because of the known
      proliferation and differentiation defects in psoriasis, we compared the calcium
      distribution of involved vs uninvolved psoriatic lesions and normal human
      epidermis. Whereas normal human and uninvolved psoriatic epidermis revealed
      increased calcium-containing precipitates in the uppermost stratum granulosum, in
      contrast the basal layer of psoriatic lesions contained less extracellular
      calcium, a condition that favored enhanced proliferation. Moreover, all psoriatic
      suprabasal cell layers displayed heavier than normal concentrations of calcium,
      indicating loss of the normal calcium gradient that programs terminal
      differentiation. This abnormal profile may account for the differentiation
      defects (eg, parakeratosis) that occur in psoriasis. Finally, psoriatic lesions
      displayed retained ionic Ca in intercellular domains of the upper stratum
      granulosum with absence of normal intercellular bilayers, findings that may
      underlie the abnormal desquamation and permeability barrier in psoriasis.

PMID- 1986709
TI  - Cutaneous manifestations of multiple myeloma.
AB  - We report the cutaneous manifestations of multiple myeloma, using a retrospective
      review of 115 patients' records obtained from tumor registry files. Five patients
      were found to have biopsy-proved extramedullary plasmacytomas without extension
      from an underlying bony focus. Twelve patients had ecchymoses without
      thrombocytopenia; two of them had biopsy-proved amyloidosis. One patient
      presented with pyoderma gangrenosum and was subsequently diagnosed with multiple
      myeloma. The last patient initially presented with what clinically appeared to be
      leukocytoclastic vasculitis, and, in the course of a standard workup, he was
      diagnosed with multiple myeloma. These findings are discussed with regard to the
      current literature on the cutaneous manifestations of multiple myeloma.

PMID- 1986710
TI  - Fibrin- and fibrinogen-related antigens in patients with venous disease and
      venous ulceration.
AB  - Abnormalities in systemic fibrinolysis have been implicated in the pathogenesis
      of venous ulceration. Patients with venous disease have a prolonged euglobulin
      lysis time and elevated plasma fibrinogen levels, yet little is known about the
      metabolism of fibrinogen and fibrin in such patients. In this study, we have used
      a technique that involves electrophoresis and densitometric analysis of captured
      fibrin-related antigens to measure the concentration and proportions of the
      individual fibrin and fibrinogen degradation products in patients with venous
      disease of the lower extremity. As a group, patients with venous disease had
      markedly elevated levels of total fibrin-related antigen and D-dimer, the
      terminal degradation product of cross-linked fibrin. Levels of D-monomer, the
      breakdown product of fibrinogen and non-cross-linked fibrin monomer, and a
      measure of fibrinogenolysis were normal in all patients. In patients with ulcers,
      the levels of D-dimer were disproportionately higher than expected from fibrin
      monomer levels. On an individual basis, significant elevations of D-dimer were
      present in six (55%) of the 11 patients with venous disease with ulcers and in
      three (43%) of the seven patients with venous disease without ulcers. We conclude
      that patients with venous disease have uniform evidence for enhanced fibrin
      formation, as evidenced by elevated levels of total fibrin-related antigen and D
      dimer. This is regardless of whether the venous disease is accompanied by
      ulceration.

PMID- 1986711
TI  - Familial multiple desmoplastic trichoepitheliomas.
AB  - A kindred with familial multiple desmoplastic trichoepitheliomas is described.
      Desmoplastic trichoepitheliomas should be added to the group of lesions that
      indicate an inherited pattern when they occur as multiple primary tumors. The
      implications for nosologic status and treatment of desmoplastic
      trichoepitheliomas are considered.

PMID- 1986712
TI  - Coexistence of spherulocytic disease (myospherulosis) and membranocystic
      degeneration.
AB  - A case of myospherulosis seen in a 22-year-old Japanese woman with lupus
      erythematosus is presented. Myospherules were found in subcutaneous nodules on
      the legs of the patient and were restricted to the areas of membranocystic
      change, a kind of degeneration of the adipose tissue. The myospherules were
      positive for blood group A antigens, suggesting a red blood cell origin. In
      contrast, the parent bodies of the myospherules were negative for blood group
      antigens. The coexistence of myospherulosis and membraneocystic changes has not
      been previously described, but might have been overlooked in the past.

PMID- 1986713
TI  - Papuloerythroderma. Another case of a new disease.
AB  - We describe a case of papuloerythroderma. This is a distinctive clinical entity
      characterized by pruritus, red-brown flat-topped papules exhibiting the "deck
      chair" sign, eosinophilia, and lymphopenia. We propose that the Langerhans cell
      may have a central role in the pathogenesis of papuloerthroderma and we describe
      an excellent response to photochemotherapy.

PMID- 1986714
TI  - Anton's syndrome in a patient with posttraumatic optic neuropathy and bifrontal
      contusions.
AB  - We describe a patient who manifested Anton's syndrome after sustaining head
      trauma that resulted in optic nerve damage and bifrontal contusions. Denial of
      monocular blindness, generalized anosognosia, and confabulation were prominent
      neurobehavioral features. Anton's syndrome is most commonly encountered in
      patients with bilateral occipital cortex lesions. Patients previously described
      who demonstrated Anton's syndrome secondary to a peripheral lesion have had an
      associated delirium or profound dementia. Our case demonstrates that Anton's
      syndrome may occur in association with blindness from a peripheral lesion, even
      in the absence of a delirium or significant dementia. We suggest that the
      bifrontal dysfunction may have been a critical factor in the production of
      Anton's syndrome. Implications for the role of frontal lobe dysfunction in the
      genesis of anosognosia and confabulation are discussed.

PMID- 1986715
TI  - Pupil-sparing oculomotor nerve palsy due to midbrain infarction.
AB  - Vasculopathic oculomotor nerve palsies with pupillary sparing are thought to be
      due to ischemic damage to the nerve in the subarachnoid space or the cavernous
      sinus. We present two cases of patients with isolated pupil-sparing oculomotor
      nerve palsies due to midbrain infarcts. Focal ischemic midbrain lesions should be
      considered in cases of pupil-sparing oculomotor nerve palsies.

PMID- 1986716
TI  - Congenital monomelic hypertrophy with progressive myopathy.
AB  - We describe a patient with congenital monomelic hypertrophy who later developed
      progressive footdrop due to a degenerative myopathy. The clinical,
      electrophysiologic, and pathologic features of the case are described and
      compared with those of a previously reported case.

PMID- 1986717
TI  - Migraine with vasospasm and delayed intracerebral hemorrhage.

PMID- 1986718
TI  - Migraine and intracerebral hemorrhage.

PMID- 1986719
TI  - Isopropyl alcohol intoxication.

PMID- 1986720
TI  - Seizures after stroke.

PMID- 1986721
TI  - Is radiosurgery all that it appears to be?

PMID- 1986722
TI  - The pathogenesis of dermatomyositis.

PMID- 1986723
TI  - Caring for the uninsured and underinsured.

PMID- 1986724
TI  - The relationship of complement-mediated microvasculopathy to the histologic
      features and clinical duration of disease in dermatomyositis.
AB  - Accumulating evidence indicates that a complement-mediated microvasculopathy may
      play a pathogenic role in dermatomyositis. In a previous study, we demonstrated
      neoantigens of the C5b-9 complement membrane attack complex in the muscle
      microvasculature of childhood and adult cases of dermatomyositis. To further
      characterize the relationship between the vascular complement deposits and
      histologic changes, quantitative histopathologic analyses were performed on 39
      dermatomyositis biopsy specimens (26 adult, 13 children). There was a significant
      correlation between the percentage of fascicles with fibers having focal
      myofibrillar loss, a change seen early in the evolution of ischemic muscle fiber
      damage, and the percentage of fascicles having capillary deposits of membrane
      attack complex. Conversely, in biopsy specimens with a higher percentage of
      fascicles with perifascicular atrophy, membrane attack complex deposits were
      significantly less common. A fascicle-by-fascicle analysis supported these
      observations. Patients whose biopsy specimens were negative for microvascular
      membrane attack complex had clinical weakness for a significantly longer time
      than those patients with vascular complement deposits. These data support the
      hypothesis that the complement-mediated vasculopathy is a primary
      immunopathogenic event in the evolution of muscle lesions in dermatomyositis.

PMID- 1986725
TI  - Initial therapy of patients with Wilson's disease with tetrathiomolybdate.
AB  - Patients with Wilson's disease who present with acute neurological symptoms often
      become clinically worse when initially treated with penicillamine. Other
      available anticopper drug therapies do not appear to offer a solution to this
      treatment problem. We are developing and evaluating a new drug, ammonium
      tetrathiomolybdate for this purpose. Theoretically, tetrathiomolybdate has
      optimal properties, including an immediate blockade of copper absorption and the
      property of forming complexes with copper in the blood, rendering the copper
      nontoxic. In this article, we present results from six patients treated with
      tetrathiomolybdate for up to 8 weeks as initial therapy. None of the five
      patients who had presented with acute neurological symptoms worsened. Also
      presented are methods of assay, preliminary stability studies, and methods of
      evaluating therapeutic end points with respect to copper metabolism.

PMID- 1986726
TI  - The neural substrate of memory impairment demonstrated by the intracarotid
      amobarbital procedure.
AB  - The intracarotid amobarbital sodium (Amytal) procedure (IAP) was performed for 46
      patients with temporal lobe epilepsy (21 with left seizure foci; 25 with right
      seizure foci). After anteromedial temporal lobectomy, neuronal densities were
      established for hippocampal subfields CA1, CA2, and CA3; the hilum; and the
      dentate granule cell layer. Intracarotid amobarbital procedure memory results
      were related to CA3 neuronal loss only. Patients who did not demonstrate memory
      after injection contralateral to the seizure focus had significantly fewer cells
      in CA3 than patients who did. Additionally, a significant correlation was
      observed between the intracarotid amobarbital procedure memory examination raw
      score after injection contralateral to the seizure focus and CA3 cell density.
      Using chi 2 analysis, significant differences were documented in the frequency
      with which memory was demonstrated after injection contralateral to the seizure
      focus for groups of patients classified by degree of CA3 neuronal loss. This
      finding supports prior research showing subfield specificity in some memory
      processes.

PMID- 1986727
TI  - Dominant-side intracarotid amobarbital spares comprehension of word meaning.
AB  - Abolition of speech production after intracarotid amobarbital injection is
      generally considered evidence for language laterality. However, complex auditory
      comprehension may be preserved after injection of the dominant (left) side. The
      possibility that this sparing may be due to the intracarotid amobarbital
      injection not adequately deactivating some of the areas responsible for speech
      comprehension in the posterior part of the hemisphere was tested with a task
      known to be critically dependent on the left posterotemporal-inferoparietal
      region, one assessing visuo-verbal semantic relatedness. Even when the
      intracarotid injection of the left side produced marked deficits of speech
      production, comprehension of semantic relations was still intact in eight of 15
      patients. Ten of these 15 patients also received right carotid injections, none
      of which affected comprehension of semantic relatedness. These data indicate that
      the intracarotid amobarbital injection cannot always specify the laterality of
      all language functions, an important concern when considering surgical procedures
      in the dominant posterotemporal-inferoparietal region.

PMID- 1986728
TI  - Memory complaints in older adults. Fact or fiction?
AB  - Complaints of poor memory by patients may be an early symptom of a pathologic
      process like Alzheimer's disease. It is therefore important to determine if
      patients' complaints of memory impairments are an accurate reflection of real
      memory disturbance. The relationship between memory complaints (metamemory) and
      objective memory performance, mood, age, verbal intelligence, and sex was
      examined in a group of 199 healthy, community dwelling adults (39 to 89 years
      old). Memory complaints demonstrated a stronger association with depressed mood
      than with performance on memory tests. Increasing reports of depressive symptoms
      were associated with more overall memory complaints. Verbal intelligence, age,
      and sex also contributed to memory complaints. Patients with higher verbal
      intelligence reported fewer complaints and placed less emphasis on forgetting.
      Older individuals reported greater frequency of forgetting and greater frequency
      of using memory techniques. Specific types of memory complaints, seriousness of
      forgetting, and types of memory aids employed are also described. These results
      showed that self-rating of memory disturbance by older adults may be related more
      to depressed mood than to poor performance on memory tests.

PMID- 1986729
TI  - On drawing impairment in Alzheimer's disease.
AB  - Spontaneous drawings of 38 patients, diagnosed by the National Institute of
      Neurological Disorders and Stroke-Alzheimer's Disease and Related Disorders
      Association criteria as "probable Alzheimer's disease," and of 39 normal control
      subjects were analyzed by two independent observers using a standardized scoring
      system. Drawings of patients with Alzheimer's disease displayed fewer angles,
      impaired perspective and spatial relations, simplification, and overall
      impairment compared with those of the control subjects. This represents a
      combination of the deficits seen following right- and left-hemisphere lesions.
      Neglect, tremor, and perseveration were not prominent. Drawing impairment was
      relatively independent of language or memory impairment, but drawing performance
      was related to perceptual and executive dysfunction in the visuospatial domain.
      Deterioration was followed up for up to 3 years.

PMID- 1986730
TI  - A trial of thiamine in Alzheimer's disease.
AB  - Because a previous short-term study demonstrated a statistically significant, but
      not clinically important, improvement in cognitive test scores during thiamine
      treatment in patients with dementia of the Alzheimer's type, a 12-month, double
      blind, parallel-group study was conducted to examine whether long-term
      administration of thiamine at 3 g/d might slow the progression of dementia of the
      Alzheimer's type. Fifteen subjects were enrolled and 10 completed the 1-year
      study. Data are available for two additional subjects through the first 9 months
      of study. No significant differences were found between the placebo and thiamine
      groups at any point during the study. In both groups, overall means for the Mini
      Mental State Examination, verbal learning, and naming scores decreased
      significantly over the 12-month study period. These results do not support the
      hypothesis that long-term administration of thiamine at 3 g/d might slow the
      progression of dementia of the Alzheimer's type.

PMID- 1986731
TI  - Nystagmus of Pelizaeus-Merzbacher disease. A magnetic search-coil study.
AB  - Magnetic search-coil oculography of three brothers with clinically diagnosed
      Pelizaeus-Merzbacher disease disclosed the presence of binocular elliptical
      pendular nystagmus in two patients in whom the waveform of the nystagmus was not
      obvious on inspection. This study, the first reported application of high
      resolution oculography to Pelizaeus-Merzbacher disease, also demonstrated primary
      position upbeat nystagmus in all three patients. The importance of finding this
      combination of elliptical pendular and upbeat nystagmus is that it is not
      described in any other childhood neurodegenerative states and, in combination
      with supportive clinical history and magnetic resonance imaging, may be so
      characteristic of Pelizaeus-Merzbacher disease that a strong presumptive
      diagnosis can be made.

PMID- 1986732
TI  - James Parkinson. On child abuse and other things.
AB  - James Parkinson, a general physician, was interested in all facets of medical
      care, and wrote two books for the lay public that contained comments on diverse
      things. He may have been one of the first physicians to publicly describe child
      abuse. Some of his advice to the public was of a neurologic nature, and included
      directions on the diagnosis and treatment of pseudoseizures, epilepsy, drowning,
      and stroke.

PMID- 1986733
TI  - Mutagenicity, carcinogenicity and toxicity of beta-naphthoflavone, a potent
      inducer of P448.

PMID- 1986734
TI  - Influence of chronic oral intake of cannabis extract on oxidative and hydrolytic
      metabolism of xenobiotics in rat.
AB  - Dietary intake of petroleum ether extract of cannabis leaves by rats in doses of
      158, 250 and 500 mg/kg in the first, second and third week, respectively, caused
      selective induction of hepatic microsomal carboxylesterases/amidases without
      affecting the renal hydrolytic activity. Acetanilide N-deacetylase, p
      nitrophenylacetate (NPA) esterase and acetylsalicylic acid (ASA) esterase I and
      II (active at pH 5.5 and 7.4) were stimulated 125, 64, 82 and 60%, respectively,
      whereas the activities of procaine esterase and acetylaminofluorene (AAF) N
      deacetylase remained unaltered. The hydrolysis of acetylcholine was also
      unchanged. Upon withdrawal of treatment microsomal hydrolytic activity receded to
      basal levels within 7 days. Curiously though, the two-fold induction of
      thiacetazone N-deacetylase (118%), a cytosolic hydrolase, remained largely
      undiminished (62%). An appraisal of the hepatic cytochrome P450 mediated
      oxidative metabolism revealed approximately three-fold induction of aromatic
      hydrocarbon hydroxylase (AHH) metabolizing benzo(a)pyrene whereas the N
      demethylation of aminopyrene was unaffected. These activities were restored to
      normal when resin administration was discontinued.

PMID- 1986735
TI  - A prenylflavone, artonin E, as arachidonate 5-lipoxygenase inhibitor.
AB  - Several naturally occurring prenylflavones were tested for their inhibitory
      actions on arachidonate 5-lipoxygenase purified from porcine leukocytes. Of the
      compounds tested, artonin E (5'-hydroxymorusin) exhibited the most potent
      inhibition on arachidonate 5-lipoxygenase (IC50 = 0.36 microM). Arachidonate 12
      lipoxygenase purified from porcine leukocytes and human platelets, 15
      lipoxygenase from rabbit reticulocytes and fatty acid cyclooxygenase from bovine
      vesicular glands were inhibited by the compound only at higher concentrations
      (IC50 = 2.3, 11, 5.2 and 2.5 microM, respectively).

PMID- 1986736
TI  - Gamma-aminobutyric acid enhancement of potassium-stimulated release of
      [3H]norepinephrine by multiple mechanisms in rat cortical slices.
AB  - Gamma-Aminobutyric acid (GABA) and GABAA agonists enhance stimulated release of
      [3H]norepinephrine [( 3H]NA) in several regions of the rat brain. In this study,
      the mechanisms by which GABA and GABAergic agonists augment potassium-stimulated
      release of [3H]NA from rat frontal cortical slices were examined. GABA enhanced
      potassium-stimulated [3H]NA release, but did not alter release of [3H]NA evoked
      by the calcium ionophore A23187, 10(-5) M, either in the presence or the absence
      of extracellular calcium. The effect of GABA on potassium-stimulated [3H]NA
      release was apparently reduced by the GABAA antagonist bicuculline methiodide,
      10(-4) M, and by the selective inhibitor of GABA uptake SKF 89976A, 10(-5) M, but
      was abolished only when bicuculline methiodide and SKF 89976A were present in
      combination. The GABAA agonist muscimol enhanced potassium-stimulated release of
      [3H]NA in a manner similar to GABA. In addition, nipecotic acid, a substrate for
      GABA uptake, enhanced potassium-stimulated [3H]NA release. Thus, GABA appears to
      enhance potassium-stimulated [3H]NA release by acting upon both GABA uptake and
      GABAA receptors. The GABAA receptors involved in this effect may be a subtype of
      GABAA receptors since they are not modulated by benzodiazepines. These results
      support the involvement of the GABA uptake carrier and the GABAA receptor in
      mediating the enhancement by GABA of potassium-stimulated [3H]NA release in the
      cortex of the rat.

PMID- 1986737
TI  - Drug binding to human erythrocytes in the process of ionic drug-induced
      hemolysis. Flow microcalorimetric approaches.
AB  - Erythrocyte hemolysis induced by cationic phenothiazine derivatives and anionic
      non-steroidal anti-inflammatory drugs was compared, by flow microcalorimetry,
      with respect to thermodynamic characteristics for drug binding to intact human
      erythrocytes. Phenothiazines having high hemolytic activities bound strongly to
      erythrocyte cells, inducing an immediate hemolytic action characterized by an
      endothermic heat effect prior to saturating available binding sites. The
      thermodynamic observable delta H and delta S fell within the ranges of -119 to 
      65.1 kJ/mol and -308 to -128 J/mol/K, respectively, for these cationic species.
      There was a linear relationship between the hemolytic activity and the degree of
      exothermicity of delta H which was enhanced significantly by the presence of a
      halogen atom(s) at the C-2 position of the phenothiazine nucleus in the order of
      H less than Cl less than CF3. Anti-inflammatory drugs, however, bound to quite
      different sites in the erythrocytes with lower affinities and higher capacities
      than cationic drugs. The latter was characterized by small negative delta H (
      17.3 to -7.1 kJ/mol) and positive delta S (10 to 41 J/mol/K). In the calorimetric
      profiles observed during hemolysis by anionic drugs, two stages were seen: the
      first, an exothermic process, arising from drug binding to the erythrocytes; the
      second, an endothermic process, corresponding to the heat of dilution of
      hemoglobin released from erythrocytes. Hemolysis occurred after the binding sites
      on the erythrocytes were saturated with drugs. Our data suggest that the binding
      activities of ionic drugs, such as the amounts of the bound drug and their
      binding energies to erythrocytes, contribute to the hemolysis.

PMID- 1986738
TI  - In vitro effects of various cholinesterase inhibitors on acetyl- and
      butyrylcholinesterase of healthy volunteers.

PMID- 1986739
TI  - Structure-activity relationships for protein binding of a series of basic non
      steroidal anti-inflammatory drugs.

PMID- 1986740
TI  - Inhibition of serine esterases in different rat tissues following inhalation of
      soman.

PMID- 1986741
TI  - Susceptibility of glucose-6-phosphate dehydrogenase deficient red cells to
      primaquine, primaquine enantiomers, and its two putative metabolites. II. Effect
      on red blood cell membrane, lipid peroxidation, MC-540 staining, and scanning
      electron microscopic studies.
AB  - The effects of primaquine (PQ), its enantiomers [(+)PQ,(-)PQ] and hydroxy
      metabolites [5-hydroxyprimaquine (5HPQ) and 6-desmethyl-5-hydroxyprimaquine
      (6D5HPQ)] on cell membranes of glucose-6-phosphate dehydrogenase (G-6-PD)
      deficient red cells were studied in vitro. There was no significant effect of PQ
      on the malonyldialdehyde (MDA) content of normal and heterozygous red cells, but
      it caused a significant increase in MDA in G-6-PD deficient red cells (P less
      than 0.05). There was no noticeable difference between the effects of the two
      enantiomers on this variable (P greater than 0.05). Compared to PQ, the hydroxy
      metabolites produced a significantly greater increase in MDA in all the groups
      studied (P less than 0.001). Of the two hydroxy metabolites, 6D5HPQ was more
      toxic than 5HPQ. Staining with MC540 showed that exposure to PQ, its enantiomers
      and two putative metabolites produced significant fluorescence, indicating that
      the drug produces marked alterations in membrane fluidity. Although the
      fluorescence was seen both in normal and heterozygous cells, the effect was
      marked in hemizygous deficient red cells (P less than 0.001). Scanning electron
      microscopic (SEM) studies revealed that PQ enantiomers had a stomatocytic effect
      on red cells of normal, heterozygous and hemizygous G-6-PD deficient red cells,
      whereas the putative metabolites had an echinocytic effect. The effects were most
      pronounced in G-6-PD deficient red cells.

PMID- 1986742
TI  - Kinetics and thermodynamics of chloroquine and hydroxychloroquine transport
      across the human erythrocyte membrane.
AB  - Chloroquine (CQ) and hydroxychloroquine (HCQ) have almost identical molecular
      volumes but showed very different permeability characteristics. The permeability
      coefficient for the unionised species of CQ (2.0 cm/sec at 25 degrees) was about
      fifty times that of HCQ (0.039 cm/sec at 25 degrees), but the apparent activation
      energy for transport (85 kJ/mol for CQ, 81 kJ/mol for HCQ) was almost identical
      for the two drugs. The partition coefficient of CQ into various organic solvents
      was much higher than for HCQ, but the different permeability behaviour cannot be
      quantitatively explained by partitioning behaviour into hexane or octanol, two
      solvents commonly used to mimic the membrane interior. A comparison of
      permeability and partitioning characteristics suggests that the barrier phase for
      these drugs within the membrane can be modelled by a mixed solvent of 5% octanol
      in hexane. The results suggest that interactions with hydrogen bonding groups
      within the membrane are important in the membrane transport of these drugs, and
      that the membrane does not behave functionally as a simple hydrocarbon barrier.

PMID- 1986743
TI  - Butyrylcholinesterase and acetylcholinesterase prophylaxis against soman
      poisoning in mice.
AB  - Human butyrylcholinesterase (BChE, EC 3.1.1.8) or acetylcholinesterase (AChE, EC
      3.1.1.7) from fetal bovine serum (FBS), administered i.v. in mice, sequestered at
      approximately 1:1 stoichiometry the highly toxic anti-ChE organophosphate, 1,2,2
      trimethylpropyl methyl-fluorophosphonate (soman). A quantitative linear
      correlation was demonstrated between blood-ChE levels and the protection
      conferred by exogeneously administered ChE. Results presented here demonstrate
      that either human BChE or FBS-AChE is an effective prophylactic measure
      sufficient to protect mice from multiple LD50S of soman without the
      administration of post-treatment supportive drugs.

PMID- 1986744
TI  - Effects of nisoldipine on recovery of coronary blood flow, sarcoplasmic reticulum
      function and other biochemical parameters in post-ischaemic porcine myocardium.
AB  - The effects of nisoldipine (0.1 micrograms/kg/min; n = 9) or its solvent (n = 9)
      were studied in pigs, in which left anterior descending coronary artery (LADCA)
      blood flow in both groups was reduced to 20% of baseline for 60 min and
      reperfused for 2 hr. Infusions were started at 30 min of ischaemia and lasted
      throughout reperfusion. In both groups, flow reduction abolished regional
      contractile function and caused similar decreases in the level of creatine
      phosphate (CP; by 70%) and the energy charge (from 0.91 to 0.69), mean arterial
      blood pressure (by 25%), LVdP/dtmax (by 30%) and cardiac output (by 30%). During
      ischaemia LADCA blood flow slightly increased (from 14 +/- 8 to 24 +/- 6
      mL/min/100 g; P less than 0.05) in the nisoldipine-treated animals, resulting in
      an increase in CP to 91 +/- 24% of baseline and preventing further decreases in
      energy charge, as observed in the solvent-treated animals. After 2 hr of
      reperfusion in neither group return of contractile function of the post-ischaemic
      myocardium was observed. Post-ischaemic blood flow in the nisoldipine-treated
      pigs increased from 24 +/- 6 mL/min/100 g to 76 +/- 14 mL/min/100 g and from 19
      +/- 6 mL/min/100 g to 41 +/- 6 ml/min/100 g in the solvent-treated animals (P
      less than 0.05) after 2 hr of reperfusion. Myocardial work was significantly
      higher in the nisoldipine-treated animals (111 +/- 15 mmHg.L/min as compared to
      69 +/- 14 mmHg.L/min in the solvent-treated pigs after 2 hr of ischaemia). The
      energy charge of the post-ischaemic myocardium was similar for both groups (0.84
      +/- 0.02 for the nisoldipine-treated and 0.83 +/- 0.03 for the solvent-treated
      animals). The rate of sarcoplasmic reticular Ca2+ uptake of the non-ischaemic
      segment of the nisoldipine-treated animals was 61% higher (P less than 0.05) than
      that of the solvent-treated animals. In the post-ischaemic myocardium similar
      rates of Ca2+ uptake were found in both groups, but the activities were markedly
      lower as compared to the non-ischaemic myocardium. It is concluded that
      nisoldipine increases blood flow during reperfusion, which may have been caused
      by coronary vasodilatation. However, attenuation of the "no-reflow" phenomenon
      also contributed, since more rapid rephosphorylation of ADP leading to an
      increase in CP during ischaemia may have preserved jeopardized cells. Moreover,
      nisoldipine increases the sarcoplasmic reticular Ca2+ pump activity independent
      of ischaemia, which may have contributed in reducing the Ca2+ overload.

PMID- 1986745
TI  - Inhibition of 12-O-tetradecanoyl phorbol-13-acetate promoted tumorigenesis by
      cepharanthine, a biscoclaurine alkaloid, in relation to the inhibitory effect on
      protein kinase C.
AB  - In two-stage mouse skin carcinogenesis initiated by 7,12
      dimethylbenz[alpha]anthracene (DMBA), cepharanthine inhibited the tumor promoting
      activity of 12-O-tetradecanoyl phorbol-13-acetate (TPA). Since Ca2(+)
      phospholipid-dependent protein kinase (PKC) was shown to be an intracellular
      target of TPA, effects of cepharanthine on the activity of this enzyme were
      investigated Cepharanthine also inhibited the phosphorylation of H1 histone by
      PKC in a concentration dependent manner. While cepharanthine inhibited the
      association of H1 histone with phospholipid vesicles, autophosphorylation of PKC
      was not inhibited by this drug. Cepharanthine also inhibited TPA-stimulated
      phosphorylation of some cytoplasmic proteins of mouse skin epidermis. These
      results indicated the possibility that anti-tumor promoting action of
      cepharanthine was the result of inhibition of PKC dependent cytoplasmic protein
      phosphorylation through the reduction of the interaction of these proteins with
      the plasma membrane.

PMID- 1986746
TI  - Specific interaction of benzimidazole anthelmintics with tubulin from developing
      stages of thiabendazole-susceptible and -resistant Haemonchus contortus.
AB  - The low- and high-affinity binding of tritiated benzimidazole anthelmintics
      (mebendazole and oxibendazole) to tubulin-containing supernatants derived from
      unembryonated eggs, third stage larvae or adult worms of thiabendazole
      susceptible and -resistant strains of Haemonchus contortus were examined and
      compared. The displacement of these radioligands by unlabelled benzimidazoles
      (mebendazole, fenbendazole, thiabendazole and oxibendazole) also was examined.
      The binding affinity, K alpha, and maximum binding, Bmax, for the high-affinity
      binding were calculated by non-linear least-square iterative curve fitting using
      a computer programme (LIGAND) based on the exact mathematical model of ligand
      receptor interactions. The K alpha was of the same order of magnitude (x 10(7) M
      1) for the susceptible and resistant eggs, larvae and worms. Resistance was
      associated with a loss of high-affinity binding. There was a 2- to 5-fold loss of
      Bmax by the resistant strain. The eggs showed greater high-affinity binding per
      milligram of protein than the larvae which, in turn, showed greater high-affinity
      binding than the adult worms. It was shown by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot analysis that the
      tubulin content per milligram of protein decreased from egg, through larvae to
      adult worm. Cross-displacement studies indicated that different benzimidazole
      drugs interacted with the same receptor (tubulin) and that a rank order of
      affinity of the benzimidazole drugs could be inferred.

PMID- 1986747
TI  - Development of an assessment guide for occupational health nurses.
AB  - Based on an expressed need for an evaluation tool or quality assurance
      measurements for occupational health programs, a committee of occupational health
      nurses was established. The committee acknowledge the importance of developing an
      evaluation tool that would be helpful to occupational health nurses in any
      setting, considering the diverse responsibilities and functions. A thorough
      review of the literature was conducted to identify available documents and
      resources for quality assurance measurements in health care facilities, and in
      particular, occupational health settings. The literature review indicated that
      most of the quality assurance programs were designed for the hospital setting.
      Utilizing the AAOHN standards, job descriptions and the AIHA audit tool for
      occupational health programs, the final 10 page assessment guide was developed
      and designed for use by occupational health nurses working alone or in a multiple
      nurse setting and by nurse managers. It is the intent of the committee that the
      assessment guide would provide a stimulus for further research and development of
      the tool by other occupational health nurse.

PMID- 1986748
TI  - Quality assurance through use of a self evaluation tool. Methods of a pilot
      study.
AB  - Quality assurance data from a valid, reliable tool can provide the occupational
      health nurse with evidence of contributions made to worker health and corporate
      goals. A committee of occupational health nurses devised a tool for quality
      assurance measurement. This tool represents a significant beginning. A pilot
      study was undertaken to test the tool. The tool itself presented barriers to
      completion. Use of a convenient sample, lack of tool completion, and a low
      response rate precluded inference or generalization. Creation of an overall
      design and approach using the research process can facilitate tool development
      and analysis. The authors encourage the refinement of this tool or the
      development of others.

PMID- 1986750
TI  - Using information to maximize loss control.

PMID- 1986749
TI  - Conjunctivitis in clean room workers. Nursing evaluation and intervention.
AB  - Conjunctivitis, in the industrial setting, can be attributed to eye contact with
      contaminated microscope oculars. Establishing a simple, convenient process for
      cleaning microscope oculars as well as educating employees and their management
      is important to reduce risk of contamination. Early identification and treatment
      of an isolated infection by the occupational health nurse and temporary exclusion
      from microscope work is essential in controlling the spread of infection and
      preventing a potential epidemic. The occupational health nurse plays a pivotal
      role in the recognition of and response to workplace health concerns and
      development of targeted strategies to promote and maintain health in the
      workplace.

PMID- 1986751
TI  - The question and the answer. Part 2: Planning for data analysis.

PMID- 1986752
TI  - Quincke's edema, revisited.
AB  - Angioneurotic edema involving the uvula is sometimes referred to as Quincke's
      edema. The term angioneurotic edema describes several closely related diseases
      manifested by recurrent, acute edema of the skin or mucosa. We report a case of
      uvular edema secondary to food allergy, treated successfully with steroids. A
      short review of angioneurotic edema and its management is also presented.

PMID- 1986753
TI  - Focal myositis. A new cause for the pediatric neck mass.
AB  - Focal myositis is an inflammatory pseudotumor of skeletal muscle that may involve
      the head and neck. It can closely mimic either a neoplastic or infectious
      process. We present the case of a 7-year-old boy with a 2-week history of a
      painful, unilateral neck swelling, fever, and torticollis. He failed to respond
      to antibiotic therapy and required an open neck exploration. An incisional biopsy
      of the indurated, inflammatory tissue adherent to his sternocleidomastoid muscle
      showed focal myositis. Focal myositis is an unusual, but important possibility in
      the differential diagnosis of any neck mass and especially one in a child.
      Although its cause is unknown, it is a self-limited disease and neither
      excisional biopsy nor radical resection is justified.

PMID- 1986754
TI  - Acquired von Willebrand's syndrome. Therapeutic and diagnostic implications.
AB  - Acquired von Willebrand's syndrome is a newly recognized bleeding diathesis
      thought to be caused by autoantibodies to the von Willebrand factor. Acquired von
      Willebrand's syndrome has been reported in association with lymphoproliferative
      disorders and benign monoclonal gammopathies. Clinical features and laboratory
      abnormalities of this disease are similar to congenital von Willebrand's disease,
      but the optimal treatment may differ. We describe a 75-year-old man with chronic
      lymphocytic leukemia and recurrent epistaxis and also discuss the pathogenesis,
      diagnosis, and treatment of both the congenital and acquired disorders.

PMID- 1986755
TI  - Pathologic quiz case 2. Angiolymphoid hyperplasia with eosinophilia.

PMID- 1986756
TI  - Pathologic quiz case 1. Lymphangiomatous macroglossia.

PMID- 1986757
TI  - Smoke and mirrors. The reaction of most hospitals to smoking policies.

PMID- 1986759
TI  - Submental surgery. A graduated approach to the aging neck.
AB  - Adequate aesthetic contouring of the aging neck often presents a difficult
      surgical challenge to the facial plastic surgeon. The apparent failure of the
      classic rhytidectomy to achieve acceptable results in the submental region has
      encouraged previous surgeons to develop surgical techniques specifically
      addressing this area. Definitive procedures were developed to treat the excess
      skin, fat, or muscle. Aesthetic results have progressively improved with the
      introduction of liposuction, judicious muscle rearrangement, and more
      conservative submental skin violation. This article describes our experience with
      these concepts and presents a useful classification devised to serve as an
      operative guide in the management of the aging neck.

PMID- 1986758
TI  - The treatment of acute external laryngeal injuries. 'State of the art'.
AB  - Guidelines are presented for the management of acute external laryngeal trauma
      based on personal experience and basic principles evolved over the past two
      decades. Accurate assessment of the extent of injury has permitted stratification
      of treatment ranging from observation to open reduction and internal fixation of
      the laryngeal skeleton. Results are often predictable and frequently lead to
      restoration of the voice and airway.

PMID- 1986760
TI  - The triple facelift. Current approach.
AB  - The combination of deep temporal facelift, subpalpebral facelift, and
      cervicofacial facelift constitutes the triple facelift. It exerts vertical
      traction with anchorage to solid anatomical landmarks, which permits perfect
      correction of ptosis. In addition, since this traction affects the upper two
      thirds of the face, the malar detachment of the cervicofacial facelift is
      considerably reduced or even nonexistent. Only the cervical phase is retained to
      reestablish the cervicomental angle. This technique, therefore, has the advantage
      of improving the quality of the result and reducing the postoperative course.

PMID- 1986761
TI  - Absence of bacteremia during nasal septoplasty.
AB  - Episodes of staphylococcal bacteremia resulting in metastatic infection have
      occurred in association with nasal septoplasty, and this has suggested the
      possible need for antimicrobial prophylaxis. In a study designed to measure the
      actual frequency with which transient staphylococcal bacteremia occurs during
      nasal septoplasty, 50 healthy patients had blood cultures drawn immediately prior
      to and during the procedure. Although 46% of the 50 patients studied had their
      nasal mucosa colonized with Staphylococcus aureus, some of the blood cultures
      obtained from the 50 patients showed bacterial growth. The authors conclude that
      staphylococcal bacteremia during nasal septoplasty is a rare occurrence, and that
      antimicrobial prophylaxis is unnecessary.

PMID- 1986762
TI  - The effects of lower lateral cartilage excision on nasal tip projection.
AB  - Nasal tip projection is an important defining feature of the nasal profile. Loss
      of projection is often the bane of the rhinoplastic surgeon. While augmentation
      techniques for maintaining or increasing tip projection are useful in selected
      patients, the majority of rhinoplasties rely on excision of cartilage,
      particularly cartilage of the cephalic border of the lower lateral crura, to
      produce the desired cosmetic result. The purpose of this study was to measure the
      effects of lower lateral cartilage excision on nasal tip projection resulting
      from three common forms of nasal tip surgery. These techniques included cephalic
      border resection without vertical dome division, cephalic border resection with
      vertical dome division, and cephalic border resection with dome division and
      suture reapproximation of the mesial crura, the so-called "Goldman tip." Despite
      the fact that overall excellent results were obtained and loss of projection was
      rarely a noticeable feature, a measurable loss of projection can be seen in all
      but one case in this series. Although loss of tip projection is usually
      acceptable due to the masking effect, the concurrent reduction in dorsal nasal
      height, loss of projection must be anticipated in excisional techniques of the
      lower lateral cartilage.

PMID- 1986763
TI  - Endoscopic ethmoidectomy and maxillary antrostomy in immunodeficient patients.
AB  - The efficacy of endoscopic sinus surgery was evaluated in 11 patients with
      diverse types of primary immunodeficiency disease and symptoms of chronic
      sinusitis. The postoperative symptoms and ability to eliminate antibiotics were
      used as outcome parameters. In two patients, the follow-up time was too short to
      assess therapeutic effectiveness. Five of the remaining nine patients had total
      or significant resolution of symptoms. Patients with transient immunodeficiency
      had the best resolution of symptoms. Eight of the total 11 patients were treated
      with intravenous immunoglobulin preoperatively, and in five patients, the
      treatment was continued postoperatively. The ability to terminate gamma-globulin
      reflects not the success of the surgery, but the transient nature of some of the
      immunodeficiencies.

PMID- 1986764
TI  - Surgical treatment of internal derangements of the temporomandibular joint. A
      long-term study.
AB  - A long-term surgical follow-up study of 176 patients (211 joints) with documented
      internal derangements of the temporomandibular joint was carried out. Arthrograms
      and tomograms were used in all cases. Forty of the patients (49 joints) were
      nonsurgical control patients. Diagnostic staging of the cases was accomplished as
      previously published. A clinical/radiologic assessment index was derived, which
      included seven measured parameters. Surgical patients, grouped by diagnostic
      stages and selected operations, were compared with each other and with control
      patients over the follow-up period (average, 8.1 years; range, 5 to 14 years).
      The surgical procedures included meniscectomy, reconstructive arthroplasty, and
      arthroplasty with temporary Silastic (Dow Corning Wright, Arlington, Tenn)
      implant. The overall success rate for surgical cases with all stages and
      procedures was 93.8%. In contrast, the control group demonstrated significant
      clinical and radiographic progression. The surgical results were stage dependent
      for the same operative procedure. Significantly better success rates were
      obtained in early-stage cases (96.9%) than in late-stage cases (89.4%). With
      respect to comparison of operative procedures, it was found that reconstructive
      arthroplasty provided results superior to those of meniscectomy. There was no
      significant difference between results obtained by meniscectomy and those by
      arthroplasty with a temporary Silastic implant. Long-term stability was excellent
      in most cases. Follow-up radiographic changes for the surgical group were less
      than expected. On the other hand, radiographic analysis of the control group
      demonstrated progressive degenerative changes in 73.5% of cases. Complications
      over the entire study were rare. It was concluded that surgery can provide
      successful long-term results in the treatment of internal derangements.

PMID- 1986765
TI  - The lower trapezius flap. Vascular anatomy and surgical technique.
AB  - The lower trapezius flap was first described in 1980 based on the transverse
      cervical artery. The older anatomical literature, however, describes the dorsal
      scapular artery as a major contributor of blood supply to the skin overlying the
      lower trapezius fibers. To clarify this, 30 dissections of this vascular region
      were performed. In 15 of 30 dissections, the dorsal scapular artery was dominant
      and the distal transverse cervical artery arose from the dorsal scapular. In nine
      of 30 dissections, the transverse cervical artery was dominant and the distal
      dorsal scapular artery arose from the transverse cervical. In six of 30
      dissections, both proximal arteries were of equal caliber with no distal
      communication. We describe a surgical technique that makes use of the lower
      trapezius flap with inclusion of the dorsal scapular artery; this technique
      greatly extends the usefulness of the lower trapezius flap, while decreasing the
      morbidity caused by division of the upper portion of the trapezius muscle during
      flap harvest.

PMID- 1986766
TI  - Cervical rotation flaps for midface resurfacing.
AB  - The midface has long served as a focus for creativity in surgical reconstruction.
      Full-thickness skin grafts, split-thickness grafts, and distal flaps have long
      been used to attempt to reduplicate existing anatomy in this area. Recent
      reconstruction efforts have focused on the creative use of microvascular free
      flaps for this purpose. This article reports on the use of extensively developed
      regional rotation flaps as an excellent reconstructive modality for use in this
      area of the face. The details of surgical incisional planning are given. The
      nuances of surgical creation of these flaps and their rotation and suspension
      into place are given. The cases we have done using this technique for the past 3
      years are reviewed. Our present indications for use of these flaps and their
      limitations are given.

PMID- 1986767
TI  - Drug response of head and neck tumors in native-state histoculture.
AB  - We describe a chemosensitivity testing of head and neck tumors, in which a native
      state histoculture, ie, a three-dimensional culture system that maintains
      important in vivo properties, including tissue architecture, was used. Fifteen
      specimens of head and neck tumors were evaluated for sensitivity to the following
      drugs: cisplatin (DDP) at concentrations of 1.5, 15, and 37.5 micrograms/mL;
      fluorouracil at concentrations of 4.0, 40, and 100 micrograms/mL; and
      combinations of cisplatin and fluorouracil in corresponding doses. Growth and
      measurement of drug responses were successfully completed in 10 specimens (five
      others were contaminated, four of them prior to instituting rigorous antibiotic
      washes). The results indicated cisplatin sensitivity in five of 10 patients;
      fluorouracil sensitivity in four of 10 patients; and fluorouracil-cisplatin
      sensitivity in seven of eight patients. Our preliminary results indicate that the
      native-state histoculture technique is feasible to test chemosensitivity of head
      and neck tumors.

PMID- 1986768
TI  - Combined use of fine-needle aspiration cytologic examination and tuberculin skin
      test in the diagnosis of cervical tuberculous lymphadenitis. A prospective study.
AB  - A prospective study to evaluate the efficacy of combined use of fine-needle
      aspiration (FNA) cytologic examination and Mantoux test in the diagnosis of
      cervical tuberculous lymphadenitis was carried out. Tuberculin reactions were
      determined in 59 control subjects. Preoperative FNA cytologic examinations and
      Mantoux tests were performed on 74 patients with cervical lymphadenopathy. The
      lymph nodes were then excised and examined histologically and cultured for
      mycobacteria. Forty-eight, 22, and 4 patients had histologically confirmed
      tuberculous, non-specific, and malignant lymphadenopathy. Fine-needle aspiration
      cytologic examination alone could detect cervical tuberculous lymphadenitis in 37
      patients (77%). The predictive value of a strong tuberculin reaction for
      mycobacterial infection was 100%. The combined use of a Mantoux test and FNA
      cytologic examination was able to diagnose 43 (90%) of 48 cases of tuberculous
      lymphadenitis cervical preoperatively. Combined use of FNA cytologic examination
      and Mantoux test was efficient in the diagnosis of tuberculous lymphadenitis.

PMID- 1986769
TI  - Assessment of middle-ear status during experimental otitis media using magnetic
      resonance imaging.
AB  - Magnetic resonance imaging has proved to be a useful tool for in vivo imaging of
      a variety of tissues. In this study, magnetic resonance imaging was applied to
      the middle ear of experimental animals with otitis media. Results showed that the
      presence and distribution of effusion within the middle-ear space could be
      readily determined. Moreover, following injection of gadolinium
      diethylenetriaminepentaacetic acid, a contrast agent, the inflamed middle-ear
      mucosa could be resolved. A comparison between magnetic resonance imaging and
      tympanometry with respect to the diagnosis of effusion showed that negative
      pressure tympanograms were equivocal (50% effusion) and that flat or normal
      tympanograms were in error in approximately 20% of the observations. These data
      document a role for magnetic resonance imaging in in vivo studies of the
      pathogenesis of otitis media with effusion.

PMID- 1986771
TI  - Intracerebral grafting: a tool for the neurobiologist.

PMID- 1986770
TI  - Plasma membrane modulation of ampullar dark cells by corticosteroids.
AB  - Individual effects of corticosteroids on the ultrastructure of rat ampullar dark
      cells were quantitatively determined. Adrenalectomized rats subsequently received
      either aldosterone or dexamethasone or only hormone solvent via miniosmotic pumps
      for a period of 14 days. Ampullar tissues of the animals were processed for
      transmission electron microscopy, and standardized regions of ampullar dark cells
      were photographed and morphometrically analyzed. Surface density and boundary
      length of basolateral membrane increased significantly after hormone substitution
      with aldosterone, but not after replacement with dexamethasone, as compared with
      animals that received only solvent. No significant differences were observed for
      other morphological parameters between the groups. This response of ampullar dark
      cells to aldosterone appears similar to that of principal cells of the collecting
      duct in comparable experimental conditions. These morphological observations
      suggest that the mineralocorticoid, aldosterone, modulates ampullar dark-cell
      membranes.

PMID- 1986772
TI  - Gap junctional communication during neuromuscular junction formation.
AB  - We have tested whether gap junctions form between nerve and muscle during their
      initial contact, before establishing the chemical synapse. Embryonic Xenopus
      stage 18-20 myotomes and neural tubes were permeabilized with DMSO to load
      appropriate reagents, dissociated, and cocultured. When myotomes, loaded with
      Lucifer yellow, were cocultured with unlabeled neural tube cells, 23% of the
      neurons contained dye after 24 hr. Affinity-purified gap junction antibodies
      loaded into myocytes or neurons reduced neuronal labeling significantly to 5%.
      [3H]uridine nucleotide transfer was observed in both directions between myocytes
      and neurons. Again gap junction antibodies substantially reduced recipient label.
      In all cases preimmune IgGs did not reduce transfer. When acetylcholine receptor
      clustering was examined in cultures containing gap junction antibodies, no
      difference in the number of neuronally induced AChR clusters was observed. This
      suggests that the cluster-inducing signal between nerve and muscle does not pass
      through gap junctions.

PMID- 1986773
TI  - Role of a key cysteine residue in the gating of the acetylcholine receptor.
AB  - We have examined changes in single-channel behavior that result from conservative
      amino acid substitutions at the Cys230 residue in the putative first
      transmembrane region (M1) of the murine nicotinic acetylcholine receptor.
      Mutations made in the gamma subunit altered the energy barrier for a single
      closing rate constant in proportion to the size of the substituted side chain.
      One of these substitutions, when made in the alpha subunits, had no effect on
      gating. No mutations altered permeation. We conclude that the region surrounding
      the M1 Cys is involved in the gating of the nicotinic acetylcholine receptor and
      that the gamma subunit contributes significantly to the control of channel
      closure.

PMID- 1986774
TI  - The retinal degeneration slow (rds) gene product is a photoreceptor disc membrane
      associated glycoprotein.
AB  - Mice homozygous for the retinal degeneration slow (rds) mutation exhibit abnormal
      development of photoreceptor cells, followed by their slow degeneration. We have
      recently cloned the rds gene and determined the structure of the wild-type rds
      mRNA. Here we show that the gene is expressed exclusively in photoreceptor cells.
      We demonstrate that it encodes a 39 kd membrane-associated glycoprotein that is
      restricted to photoreceptor outer segments. By electron microscopy, we show that
      the rds protein is distributed uniformly within outer segment discs. The
      developmental appearance of the rds protein coincides with outer segment disc
      formation. We propose that the rds protein functions as an adhesion molecule for
      stabilization of the outer segment discs.

PMID- 1986775
TI  - Synthesis and secretion of high- and low-molecular-weight forms of the enzyme
      releasing peptide (ERP) from the macrophage-like cell line THP-1.
AB  - Neutrophil enzymes have been implicated as a source of lung injury in patients
      with the adult respiratory distress syndrome (ARDS) and with emphysema. We
      studied a human alveolar macrophage-derived peptide messenger, the enzyme
      releasing peptide (ERP), which causes neutrophils to secrete their enzymes. The
      secretion and synthesis of ERP was studied in human alveolar macrophages and in
      the macrophage-like cell lines THP-1, HL-60, and U937. All four cell types
      secrete an ERP-like peptide. THP-1 cells secrete a higher concentration of the
      peptide than do macrophages. The secretion of ERP by THP-1 is suppressed by the
      protein synthesis inhibitors actinomycin D and cycloheximide. While the
      macrophages secrete ERP, they do not synthesize it. These studies suggest that
      ERP is synthesized by an alveolar macrophage precursor and stored in the mature
      macrophage for later release. 12-O-tetradecanoylphorbol-13-acetate (TPA)
      suppresses ERP secretion by THP-1 cells, but it does not modify secretion in
      macrophages. Escherichia coli-derived lipopolysaccharide and dimethyl sulfoxide
      do not modify secretion in either cell type. The THP-1 cells secrete a high- and
      low-mass-ratio (Mr) form of ERP-like proteins. The low Mr but not the high Mr
      form stimulates neutrophils to secrete their granule enzymes. We conclude that
      human alveolar macrophages secrete ERP but do not synthesize it. It is likely
      that ERP is made by an alveolar macrophage precursor in a high Mr form that is
      cleaved prior to secretion by the macrophages.

PMID- 1986776
TI  - Effects of activated polymorphonuclear leukocytes upon pulmonary surfactant in
      vitro.
AB  - Current evidence suggests that products of activated inflammatory cells cause or
      contribute to the acute lung injury of the adult respiratory distress syndrome
      (ARDS). To assess the possibility that these products may impair surfactant
      function during ARDS, we exposed surfactant in vitro to polymorphonuclear
      leukocytes (PMN) activated by phorbol myristate acetate and to the oxidant
      producing pair ferric chloride/ascorbate (FeCl3/ASC). After incubation of
      surfactant with 8 to 32 x 10(6) activated PMN for 1 to 4 h or with FeCl3/ASC for
      16 h, its isopycnic density (d), minimum surface tension (gamma min), time course
      of adsorption, compressibility (SC), and stability index (SI) were determined. We
      found progressive decreases of d, adsorption, and SI and progressive increases of
      gamma min and SC after exposure to activated PMN in increasing numbers or for
      longer time periods. Superoxide dismutase completely inhibited all of these
      effects except the decreased adsorption, which it did not significantly inhibit.
      Similar changes in all of these parameters occurred after exposure of surfactant
      to FeCl3/ASC. Polyacrylamide gel electrophoresis of surfactant after exposure to
      activated PMN showed a decrease of the major apoprotein that progressed with
      exposure time and was associated with the appearance of several bands with both
      lower and higher molecular weights than that of the apoprotein. The data show
      that activated PMN are capable of impairing surfactant function in vitro and of
      degrading the major apoprotein. They suggest that the effects upon d, gamma min,
      SC, and SI are mediated largely if not exclusively by oxidant radicals. While
      oxidants may contribute to delayed adsorption, proteolysis appears to play the
      principal role in this effect.

PMID- 1986777
TI  - Lymphocyte chemokinetic factors derived from human tonsils: modulation by 1,25
      dihydroxyvitamin D3 (calcitriol).
AB  - Although interleukin (IL)-2 may in part be responsible for lymphocyte
      accumulation to sites of active sarcoidosis, other cytokines that control such
      recruitment are not well characterized. Similarly, the pathogenic rationale for
      the ability of sarcoid macrophages to produce 1,25-dihydroxycholecalciferol
      (calcitriol) is not understood. We studied the release of chemokinetic
      lymphokines from human nylon wool-non-adherent tonsillar lymphocytes (HNTLs)
      employing a standard in vitro lymphocyte migration assay. If mitogen-stimulated
      HNTL supernatants were fractionated by high-performance liquid chromatography,
      five positive and one negative chemokinetic factors could be identified. The five
      lymphocyte chemoattractant factors (LCFs) ranged in mol wt from 5 to 35 kD and
      stimulated the in vitro migration of nonsensitized human lymphocytes by 200 to
      500%. The LCFs appeared distinct from IL-2, IL-1, or gamma-interferon. Co
      incubation of HNTLs with mitogen and 1 nM calcitriol prevented the production or
      release of two of the LCFs and significantly decreased the quantity of a third
      LCF. Calcitriol also resulted in the appearance of a second negative chemokinetic
      factor, lymphocyte migration inhibitory factor (LyMIF). Combined with our
      previous studies demonstrating that calcitriol interferes with IL-2-induced
      lymphocyte migration, these results provide a rationale for an anti-inflammatory
      role for calcitriol in sarcoidosis and other granulomatous disorders. These
      experiments also demonstrate that the control of lymphocyte recruitment to
      inflammatory foci is multifactorial.

PMID- 1986778
TI  - Distribution of endothelin-like immunoreactivity and mRNA in the developing and
      adult human lung.
AB  - Localization and characterization of endothelin-producing cells in the developing
      (fetal and postnatal) and adult human lung was investigated using the technics of
      immunocytochemistry and in situ hybridization. Immunoreactivity for endothelin
      was seen mainly in pulmonary endocrine cells of developing human lung.
      Immunoreactivity was also seen in the airway epithelium in fewer cases (about
      50%) of human adults. In situ hybridization with 35S- or 32P-labeled RNA probes
      complementary to endothelin-1, -2, and -3, showed that endothelin mRNAs were
      expressed in a number of cells that were in similar sites to endocrine cells.
      Immunocytochemistry and in situ hybridization employed on pairs of reverse-face
      serial sections showed the presence of endothelin immunoreactivity and mRNAs in
      the same endocrine cell. Correlative studies revealed that endothelin is co
      localized with general endocrine markers (synaptophysin, chromogranin, protein
      gene product 9.5) and regulatory peptides (e.g., gastrin-releasing peptide). The
      density (cells/mm2) of endocrine cells containing immunoreactivity or mRNAs was
      highest during fetal life and started to decline before birth, and was minimal in
      adults. Endothelin-like immunoreactivity and mRNAs were also expressed in
      endothelial cells. From these results, it is concluded that endothelin is
      synthesized in endocrine cells of human lung and the change of developmental
      expression of this peptide suggests it may play a part in growth regulation in
      addition to its putative vasoconstrictor role in human lung.

PMID- 1986779
TI  - Development of alveolar septa and cellular maturation within the perinatal lung.
AB  - To quantitate fetal lung cellularity and regional variation in alveolar
      maturation, guinea pig lungs were studied at 55, 60, and 65 d of gestation or
      within 2 h of birth (term = 68 d), and the data were analyzed for intralobar,
      interlobar, and age-group differences. Nine blocks from each left cranial and
      caudal lobe were all measured for volume, numerical, and surface densities in
      tissue (Vv(i,t), Nv(i,t), and Sv(i,t], and total volumes, numbers, and surface
      areas per lung (V, N, and S) of type I and type II epithelia, presumptive
      progenitor epithelium (cuboidal cells lacking lamellar bodies [LB]),
      interstitium, and endothelium. Total fixed lung volume, VL, increased 3-fold from
      day 55 through birth. At each age, there were no consistent intralobar or
      interlobar differences in Vv(i,t), Nv(i,t), or Sv(i,t) for any cell type. Within
      a septal tissue volume of 580 to 670 microliters at all ages, the N and V of type
      I cells did not vary with age, although their S increased from 1,240 cm2 at day
      55 to 3,967 cm2 at birth. The N of morphologic type II cells per lung increased 7
      fold from day 55 to day 60 and was constant thereafter, while the N of cuboidal
      cells decreased proportionally; type II cells contained only 4.8% (vol/vol) of LB
      at 55 d compared to 18.0% at birth. The N and V of interstitium did not vary by
      age. While endothelial V was constant over these ages, endothelial S increased
      from 897 cm2 to 3,398 cm2, and the V of capillary blood and the V of alveolar
      airspace each increased 4-fold.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1986780
TI  - Attachment of influenza A virus to ferret tracheal epithelium at different
      maturational stages.
AB  - Influenza virus attaches primarily to ciliated cells in mature airways
      epithelium. This process is mediated by a viral envelope glycoprotein
      (hemagglutinin) that binds to sialic acid-containing receptors in the apical
      membrane of host cells. The purpose of this study was to determine the cellular
      distribution of these receptors as a function of tracheal epithelial maturation
      in the ferret, which is susceptible to influenza virus infection at all ages and
      undergoes postnatal ciliation. To assay for virus attachment, tracheal strips
      from ferrets at ages 0, 7, 14, and 28 d were incubated at 4 degrees C for 1 h
      with a concentrated suspension of influenza A virus. Transmission electron
      microscopy demonstrated virus attachment to the apical surface of 77 to 87% of
      ciliated cells, but only to 1 to 9% of nonciliated surface epithelial cells at
      all ages, including the newborn, which has few ciliated cells (less than 10% of
      total cells). Virions also attached to most of the preciliated cells identified.
      Pretreatment of tracheal strips with neuraminidase virtually eliminated viral
      attachment. These findings demonstrate preferential influenza virus binding to
      sialylated receptors on ciliated cells and their immediate precursors. The
      sparsity of ciliated cells with no evidence for increased influenza virus binding
      per cell in newborn ferret tracheas suggests that the previously demonstrated
      high risk of death from influenza infection in newborn ferrets is due to factors
      other than increased susceptibility to virus attachment. Influenza virus
      receptors appear to be selective membrane markers for ciliated cells and may be
      particularly useful for the identification of preciliated cells.

PMID- 1986781
TI  - Structural comparison of recombinant pulmonary surfactant protein SP-A derived
      from two human coding sequences: implications for the chain composition of
      natural human SP-A.
AB  - The pulmonary surfactant-associated protein SP-A is encoded by presumably two
      different genes, resulting in slightly different amino acid sequences. Both gene
      products were expressed in Chinese hamster ovary cells. Their macromolecular
      structure differed significantly. SP-A alpha 3 exhibited a much higher amount of
      tetrameric to hexameric structures than SP-A alpha 2, for which dimeric
      structures predominate. These differences may be caused by the higher expression
      rates of SP-A alpha 3 presumably due to the presence of introns in the sequence.
      The occurrence of irregular disulfide links between individual oligomeric SP-A
      molecules composed of alpha 3-chains together with the demonstrated presence of
      both gene products in natural human SP-A suggest that the subunits of SP-A are
      heterotrimers of one alpha 2- and two alpha 3-chains.

PMID- 1986782
TI  - Primary structure and analysis of the location of the regulatory disulfide bond
      of pea chloroplast NADP-malate dehydrogenase.
AB  - Purified pea chloroplast NADP-malate dehydrogenase (S)-malate: NADP+
      oxidoreductase, EC 1.1.1.82) was digested with trypsin and the resulting peptides
      were separated by HPLC and sequenced. Together with the information from earlier
      work (Fickenscher, K. et al. (1987) Eur. J. Biochem. 168, 653-658) the total
      sequence is not known to an extent of 78%. Comparison with the sequence of the
      corn NADP-malate dehydrogenase deduced from its cDNA (Metzler, M.C. et al. (1989)
      Plant Mol. Biol. 12, 713-722) showed 84% agreement; however, the 11 N-terminal
      residues exhibit only 27% similarity. The N- and C-terminal extrapeptides of the
      pea NADP-malate dehydrogenase when aligned with non-regulatory NAD-malate
      dehydrogenases from bacteria or mammals consist of 30 and 17 amino acids,
      respectively. Since all cysteine-containing peptides were sequenced, the number
      of eight cysteines per subunit of the pea enzyme was established. The native,
      oxidized enzyme is characterized by an extremely slow reactivity of two thiols.
      Titration of the thiols of the denatured, oxidized enzyme both with DTNB and with
      pCMB resulted in six thiols not involved in disulfide formation. Therefore, one
      disulfide bridge must be present per 38.9 kDa subunit. Analysis of disulfide
      bonds by urea gel electrophoresis confirmed this finding. Using digestion
      products of NADP-malate dehydrogenase with aminopeptidase K, the location of the
      single disulfide bridge was established to be on the N-terminal arm (Cys-12 and
      Cys-17) of the polypeptide chain.

PMID- 1986783
TI  - Secondary structure perturbations in salt-induced protein precipitates.
AB  - The secondary structure implications of precipitation induced by a chaotropic
      salt, KSCN, and a structure stabilizing salt, Na2SO4, were studied for twelve
      different proteins. alpha-helix and beta-sheet content of precipitate and native
      structures were estimated from the analysis of amide I band Raman spectra. A
      statistical analysis of the estimated perturbations in the secondary structure
      contents indicated that the most significant event is the formation of beta-sheet
      structures with a concomitant loss of alpha-helix on precipitation with KSCN. The
      conformational changes for each protein were also analyzed with respect to
      elements of primary, secondary and tertiary structure existing in the native
      protein; primary structure was quantified by the fractions of hydrophobic and
      charged amino acids, secondary structure by x-ray estimates of alpha-helix and
      beta-sheet contents of native proteins and tertiary structure by the dipole
      moment and solvent-accessible surface area. For the KSCN precipitates, factors
      affecting beta-sheet content included the fraction of charged amino acids in the
      primary sequence and the surface area. Changes in alpha-helix content were
      influenced by the initial helical content and the dipole moment. The enhanced
      beta-sheet contents of precipitates observed in this work parallel protein
      structural changes occurring in other aggregative phenomena.

PMID- 1986784
TI  - General occurrence of binding to acetylcholinesterase-substrate complex in
      noncompetitive inhibition and in inhibition by substrate.
AB  - To assess the relative importance of binding to enzyme-substrate complex (E.S)
      and to acetylenzyme (EA), noncompetitive inhibition has been studied in
      hydrolysis by acetylcholinesterase (AcChE) of cationic and uncharged substrates -
      acetylcholine (AcCh), 3,3-dimethylbutyl acetate, n-butyl acetate, 2
      (methylammonio)ethyl acetate, 2- (N,N-diethyl-N-n-butylammonio)ethyl acetate
      (DEBAAc) and 2-(methylsulfonyl)ethyl acetate. For the N-trimethyl quaternary ions
      related to AcCh, tetramethylammonium ion, choline and choline ethyl ether,
      noncompetitive inhibition (Ki(nonc) is more favorable with the slower substrates
      than with AcCh, i.e., when E.S greater than EA, and is attributed to formation of
      enzyme-substrate-inhibitor complexes, E.S.I'. Noncompetitive inhibition by
      tetraethyl-, tert-butyl- and isopropylammonium ions, and acetamidocholine and its
      lower dimethyl analogue, is also attributed to E.S.I' complexes. Peripheral
      binding of these inhibitors decreases acylation more than deacylation. Some
      tertiary dimethylamonio ions have more favorable Ki(nonc) values with AcCh,
      decreasing deacylation more than acylation. The substrate DEBAAc is a more
      effective noncompetitive than competitive inhibitor in hydrolysis of AcCh,
      indicating that it binds more strongly in a peripheral site than in the active
      site of the free enzyme. In its hydrolysis by AcChE, it acts as its own
      noncompetitive inhibitor, by this non-productive binding. Formation of E.S.I'
      complexes is a general characteristic of hydrolysis by AcChE and decrease in
      rates at high concentrations of AcCh and related substrates is attributed to
      peripheral regulatory site binding, formation of E.S.S' complexes, rather than to
      binding to the acetylenzyme.

PMID- 1986785
TI  - Purification of ferrichrome synthetase from Aspergillus quadricinctus and
      characterisation as a phosphopantetheine containing multienzyme complex.
AB  - Aspergillus quadricinctus was grown under iron limitation to induce the enzymes
      for ferrichrome biosynthesis. The mycelium was disintegrated by ultraturrax
      homogenization, and ferrichrome synthetase was purified by column chromatography
      on DEAE cellulose, hydroxyapatite and Bio-Gel A-5m. The enzyme was almost
      homogeneous in single fractions as shown in gel electrophoresis under non
      denaturating conditions. By fast-protein liquid chromatography on Superose 6, the
      purified ferrichrome synthetase (molecular weight 9.6.10(5) dissociated partly
      into an enzyme complex with reduced ferrichrome synthetase activity of 8 x 10(5)
      Da, one acetylhydroxyornithine (AHO) activating protein of 5.5 x 10(5) Da and one
      glycine activating protein of 4 x 10(5) Da. After SDS treatment the AHO
      activating protein dissociated into subunits of 9 x 10(4) Da, while the glycine
      activating protein dissociated into subunits of 5 x 10(4) Da and 4 x 10(4) Da in
      a molar ratio of 6:1. No subunits were found after SDS treatment of the larger of
      the two ferrichrome synthetizing enzyme complexes. Pantetheine was detected in
      protein bands of defined molecular weights (4 x 10(4), 9 x 10(4) and greater than
      3.4 x 10(5) after SDS polyacrylamide gel electrophoresis. Gel slices were cut
      out, and the growth factor activity for Lactobacillus plantarum ATCC 8014 was
      analyzed. The calculated content was 2 mol of pantetheine per mol of ferrichrome
      synthetase of 9.6 x 10(5) Da.

PMID- 1986786
TI  - p-Butyroxybenzenediazonium fluoroborate, substrate of acetylcholinesterase and
      butyrylcholinesterase, discriminates between the two enzymes by a specific
      affinity labelling.
AB  - p-Butyroxybenzenediazonium fluoroborate 1 was shown to be a substrate of both
      acetylcholinesterase (AcChE) and butyrylcholinesterase (BuChE) with Michaelis
      constants of 6.10(-5) M and 1.3. 10(-4)M, respectively. Upon incubation in the
      dark, 1 was able to discriminate between the two enzymes AcChE was efficiently
      inactivated in a time-dependent manner while BuChE remained unaffected. Kinetic
      analysis of the inactivation of AcChE (i) by various concentrations of 1
      indicated that it behaves as an affinity label, (ii) at three different pH levels
      suggested that the pKa of the labelled residue was higher than 7 and (iii) in the
      presence of different selective ligands for either the active site (edrophonium)
      or the peripheral site (propidium) indicated that 1 alkylated the active site
      rather than the peripheral one. Differences of reactivity between AcChE and BuChE
      suggest a different positioning and/or a different chemical environment of the
      substrate within two active sites.

PMID- 1986787
TI  - Proteinase isoinhibitors from bovine spleen: primary structure of an intermediate
      in the processing of the precursor.
AB  - The complete amino acid sequence of the proteinase inhibitor III from bovine
      spleen is reported. It consists of 62 amino acid residues and is identical to
      that of spleen inhibitor II (an isoinhibitor of the bovine pancreatic trypsin
      inhibitor, which shares with the latter 89% of sequence identity), except for
      four extra residues at the C-terminal side. Inhibitor III appears to be an
      intermediate in the processing of the putative 100-residue primary expression
      product, which leads to the mature inhibitor II. These results and those
      previously obtained for another intermediate, isoinhibitor I, are indicative of
      the following order for the last steps of the precursor processing inhibitor I---
      inhibitor III----inhibitor II. The mature protein and the two intermediates
      isolated have a very similar antiproteolytic activity. However, their in vivo
      target enzyme(s) are not yet known, as also the target enzyme of the bovine
      pancreatic trypsin inhibitor is not known. Thus, the available data would
      indicate that either the three isoinhibitors have a distinct functional role, by
      inhibiting different target enzymes, or inhibitors I and III are obligatory
      intermediates for directing the final targeting of the mature, functionally
      relevant inhibitor II.

PMID- 1986788
TI  - Photometric or fluorometric assay of cathepsin B, L and H and papain using
      substrates with an aminotrifluoromethylcoumarin leaving group.
AB  - N-trifluoromethylcoumarinylamide derivatives of benzyloxycarbonyl-Arg-Arg,
      benzyloxycarbonyl-Phe-Arg and Arg are convenient chromogenic and fluorogenic
      substrates of cathepsin B, L and H, respectively. Benzyloxycarbonyl-Phe-Arg-N
      trifluoromethylcoumarinylamide is also a highly sensitive substrate for papain.

PMID- 1986789
TI  - The characterisation of immobilised lignin peroxidase by flow injection analysis.
AB  - Immobilised lignin peroxidase has been investigated using a flow system in the
      steady state and by flow injection analysis (FIA). In the steady state, the
      extreme sensitivity of the enzyme towards inactivation by H2O2 resulted in a
      stable response only in the presence of saturating levels of organic substrate
      and at very low (10 microM) peroxide concentrations. By contrast, the low contact
      time during FIA led to a stable response to injections of 100 microM H2O2. At
      higher peroxide concentrations a reproducible inactivation was observed, allowing
      a study of factors affecting both activity and stability. Lignin peroxidase
      substrates that undergo at least semi-reversible oxidation/reduction, including
      high-molecular-weight lignin fractions, could be detected by electrochemical
      reduction of the oxidation products. With this detection system it was possible
      to demonstrate the role of veratryl alcohol as mediator. This mediated oxidation
      of lignin functioned only when all components were present simultaneously, and
      was not observed when lignin was separated from the site of veratryl alcohol
      oxidation.

PMID- 1986790
TI  - Effects of uric acid in aqueous phase on neutrophil alkaline phosphatase.
AB  - In vitro effects of uric acid (2-6-8 trioxypurine) on purified human neutrophil
      alkaline phosphatase were studied. A marked activation of the enzyme catalyzed
      reaction is observed. This activation is dose and pH dependent and not influenced
      by dialysis. Uric acid can form a stable complex with alkaline phosphatase, whose
      biochemical characteristics (heat stability, reactivity towards some inhibitors)
      are significantly modified.

PMID- 1986791
TI  - Proteolytic modification of neural cell adhesion molecule (NCAM) by the
      intracellular proteinase calpain.
AB  - The neural cell adhesion molecule, NCAM, is concentrated in synaptic regions and
      thus may contribute to the formation and maintenance of connections between brain
      cells. We present evidence that the cytoplasmic domain of NCAM can be
      experimentally modified by the intracellular calcium-dependent proteinase,
      calpain. This degradation could provide a mechanism for rapidly uncoupling and
      reorganizing synaptic contacts.

PMID- 1986792
TI  - The effect of palmitoyl-CoA binding to albumin on the apparent kinetic behavior
      of carnitine palmitoyltransferase I.
AB  - Substrate saturation plots of carnitine palmitoyltransferase I activity from
      isolated rat liver mitochondria vs. palmitoyl-CoA concentration in the presence
      of bovine serum albumin have been reported to yield sigmoidal kinetics. Under
      identical assay conditions we have confirmed these observations as reflected by
      nonlinear Lineweaver-Burke plots (1/vi vs. 1/[S]) an average Hill coefficient of
      napp. = 1.98 +/- 0.09 (Mean +/- S.E. from four separate experiments). For these
      determinations the enzyme activity was plotted against the total [palmitoyl-CoA]
      in the presence of 0.13% bovine serum albumin. Utilizing the total [palmitoyl
      CoA] to determine the kinetic properties of carnitine palmitoyltransferase I
      would be valid only if the relationship between total and free [palmitoyl-CoA]
      was linear, which is not the case as we have previously shown. When carnitine
      palmitoyltransferase I substrate saturation kinetics were reanalyzed using the
      previously determined free [palmitoyl-CoA]'s, the plots revealed a shift to
      standard hyperbolic kinetics. This observation was confirmed by an average Hill
      coefficient of napp. = 1.04 +/- 0.10 (Mean +/- S.E.) and linear Lineweaver-Burke
      plots. The double-reciprocal plots from these analyses yielded an average S0.5 of
      2.55 +/- 0.82 microM (Mean +/- S.E.) palmitoyl-CoA and Vmax of 19.69 +/- 5.48
      nmol/min per mg protein. These studies clearly demonstrate the importance of
      defining the free [palmitoyl-CoA] when analyzing the kinetics of carnitine
      palmitoyltransferase I in the presence of bovine serum albumin.

PMID- 1986793
TI  - Isolation, characterization and partial amino acid sequence of a chloroplast
      localized porphobilinogen deaminase from pea (Pisum sativum L.).
AB  - Porphobilinogen deaminase catalyzes the condensation of four porphobilinogen
      monopyrrole units into hydroxymethylbilane, a linear tetrapyrrole necessary for
      the formation of chlorophyll and heme in higher plant cells. We report the
      purification to homogeneity of a chloroplast-localized form of the enzyme from
      pea (Pisum sativum L.) by a novel purification scheme involving dye-ligand
      affinity chromatography. The purified chloroplast porphobilinogen deaminase
      consists of a single polypeptide with a relative molecular mass of 36-45 kDa as
      determined by size-exclusion chromatography and sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. The isoelectric point of the protein is
      acidic. The activity of the enzyme shows different levels of sensitivity to
      divalent cations and is most sensitive to FE2+. The amino terminus of pea enzyme
      has been obtained by microsequencing and determined to bear little similarity to
      the amino acid sequences of porphobilinogen deaminases purified from other
      organisms. Polyclonal antisera elicited against the purified protein has been
      used to examine the abundance and cellular distribution of the enzyme.

PMID- 1986794
TI  - 1H-NMR study and structure determination of 4,4- and 4,6-dimers from
      electrochemical reduction of NADP+.
AB  - The products arising from one-electron electrochemical reduction of the coenzyme
      nicotinamide adenine dinucleotide phosphate (NADP+) have been studied by HPLC
      chromatography and 1H-NMR spectroscopy. HPLC and NMR analyses have shown seven
      dimeric species, the most abundant of which (40%) has been isolated and has
      resulted to be an NADP 4,4-linked dimer. The other two diastereoisomeric 4,4
      dimers present for the 25% and 10%, respectively, have been detected in the crude
      reaction mixture, but have not been isolated. The 4,4-tetrahydrobipyridine
      structure and the stereochemistry at the ring-ring junction for these three
      isomers have been determined on the basis of their NMR parameters. Preparative
      HPLC chromatography also led to two fractions enriched in another four dimers,
      present in the crude mixture, which turned out to have a 4,6-tetrahydrobipyridine
      structure. All the chemical shifts and the H,H coupling constants of the 4,4- and
      4,6-tetrahydrobipyridine systems have been obtained for the seven compounds. For
      the most abundant among the 4,4-dimers the NMR analysis also gave the coupling
      constant values of the ribose-diphosphate chain.

PMID- 1986795
TI  - The stabilizing influence of divalent ions and Na+ on the di-decameric structure
      of Yoldia limatula hemocyanin.
AB  - The stabilizing influence of Ca2+, Mg2+, Ba2+ and Na+ on the di-decameric
      structure of the hemocyanin of the bivalve, Yoldia limatula has been investigated
      by light-scattering molecular weight measurements and by analytical
      ultracentrifugation. The molecular weight (Mw) data, examined as a function of
      decreasing divalent ion and sodium ion concentrations at pH 8.0 and at a constant
      hemocyanin concentration of 0.10 g.l-1, show biphasic transition profiles, with a
      sharp initial decline in Mw as the concentration of the stabilizing cations is
      reduced. The analysis of the molecular weight data is best described in terms of
      the four-species, di-decamer-decamer-dimer-monomer scheme of association
      dissociation equilibria. About 25 to 35 bound divalent ions and about 10 bound
      Na+ ions per half-molecule or decamer are required in order to account for the
      initial step of the observed transitions. The subsequent transitions representing
      the decamer to dimer and the dimer to monomer steps of the reaction account for
      the additional binding of three to four and two to four cations per dimer and per
      monomer, respectively. The relatively large number of divalent ions per decamer
      suggests strong ionic stabilization of the decamer to decamer contacts within the
      parent di-decameric assembly of Yoldia hemocyanin. This is consistent with
      earlier observations showing relatively few hydrophobic groups at the decamer to
      decamer contact areas.

PMID- 1986796
TI  - Amino acid sequence and molecular modelling of a thermostable two (4Fe-4S)
      ferredoxin from the archaebacterium Methanococcus thermolithotrophicus.
AB  - The amino acid sequence of a two (4Fe-4S) ferredoxin from the methanogenic
      bacterium Methanococcus thermolithotrophicus (FdMt) has been determined. This
      thermostable protein comprises 60 amino acid residues (Mr 6541) and two (4Fe-4S)
      clusters chelated to the protein through the eight cysteines. FdMt contains a
      relatively high number of lysines [5], threonines [4] and valines [10]. The three
      dimensional molecular model generated from the Peptococcus aerogenes X-ray
      structure keeps the characteristic overall ferredoxin folding thanks to
      complementary substitutions of residues of the hydrophobic core. The major
      structural features of the model are the different environments of both clusters,
      and the patch of three lysines at one end of the molecule. The possible role of
      several structural factors in the thermostability of the protein is discussed.

PMID- 1986797
TI  - Functional consequences of substitution of the active site (phospho)histidine
      residue of Escherichia coli succinyl-CoA synthetase.
AB  - Succinyl-CoA synthetase (EC 6.2.1.5, succinate:CoA ligase (ADP-forming] of
      Escherichia coli is an alpha 2 beta 2 tetramer, with the active site believed to
      be located at the point of contact between the two subunit types. It has been
      previously established that the reaction involves the intermediate participation
      of a phosphorylated enzyme form in the process of catalysis. The site of
      phosphorylation (His-246) and the binding sites for the substrates ADP and ATP
      are located in the alpha subunit, and the succinate and CoA binding sites are in
      beta. A mutant form of this enzyme, with the active site histidine residue
      replaced by aspartate, has been produced in large quantities and purified to
      homogeneity. This form appears to be indistinguishable from the native enzyme
      with respect to its subunit assembly, but has no ability to catalyze the overall
      reaction. As expected, the His-246 alpha----Asp mutant is incapable of undergoing
      phosphorylation. We have developed an assay based upon the arsenolysis of
      succinyl-CoA that effectively isolates the partial reaction that occurs in the
      portion of the active site contributed by the beta subunit; this reaction does
      not involve covalent participation of His-246 alpha. We have found that the His
      246 alpha----Asp mutant is also devoid of activity in this arsenolysis reaction,
      indicating that an intact His-246 alpha is required for the establishment of the
      microenvironment in this portion of the active site that is required for the
      corresponding step of the overall reaction.

PMID- 1986798
TI  - Tissue kallikrein processes small proenkephalin peptides.
AB  - Tissue kallikrein may play a role in processing precursor polypeptide hormones.
      We investigated whether hydrolysis of natural enkephalin precursors, peptide F
      and bovine adrenal medulla docosapeptide (BAM-22P), by hog pancreatic kallikrein
      is consistent with this concept. Incubation of peptide F with this tissue
      kallikrein resulted in the release of Met5-enkephalin and Met5-Lys6-enkephalin.
      Met5-Lys6-enkephalin was the main peptide released, indicating that the major
      cleavage site was between two lysine residues. At 37 degrees C and pH 8.5, the KM
      values for formation of Met5-enkephalin and Met5-Lys6-enkephalin were 129 and 191
      microM, respectively. Corresponding kcat values were 0.001 and 0.03 s-1 and
      kcat/KM ratios were 8 and 1.6.10(2) M-1.s-1, respectively. Cleavage of peptide F
      at acidic pH (5.5) was negligible. When BAM-22P was used as a substrate, Met5
      Arg6-enkephalin was released, thus indicating cleavage between two arginine
      residues. At pH 8.5, KM was 64 microM, kcat was 4.5 s-1, and the kcat/KM ratio
      was 7.10(4) M-1.s-1. At 5.5, the pH of the secretory granules, KM, kcat and
      kcat/KM were 184 microM, 1.9 s-1 and 10(4) M-1.s-1, respectively. It is unlikely
      that peptide F could be a substrate for kallikrein in vivo; however, tissue
      kallikrein could aid in processing proenkephalin precursors such as BAM-22P by
      cleaving Arg-Arg peptide bonds.

PMID- 1986799
TI  - Pregnancy zone protein, a proteinase binding alpha-macroglobulin. Stopped-flow
      kinetic studies of its interaction with chymotrypsin.
AB  - Human pregnancy zone protein (PZP) is a major pregnancy-associated plasma
      protein, strongly related to alpha 2-macroglobulin (alpha 2M). The proteinase
      binding reaction of PZP is investigated using chymotrypsin as a model enzyme. The
      time-course of the interaction is studied by measuring the change in intrinsic
      protein fluorescence of PZP-chymotrypsin reaction mixtures as a function of time
      after rapid mixing in a stopped-flow apparatus. Titrations show the changes of
      fluorescence at equilibrium to correspond with the formation of a chymotrypsin
      PZP(tetramer) species. The kinetic results show the formation of the species to
      take place in an overall second-order process dependent on the concentrations of
      chymotrypsin and of PZP(dimers), k = 5 x 10(5) M-1 x s-1. Reactions of PZP-thiol
      groups do not give rise to fluorescence changes. The fluorescence changes most
      likely reflect the formation of an intermediate with intact thiol esters. Further
      analysis of the kinetic results suggests that the chymotrypsin-PZP(tetramer)
      intermediate is formed in two reaction steps: (1) initially native PZP(dimers)
      are cleaved at bait regions by enzyme molecules, and that is the rate determining
      reaction of the fluorescence changes; (2) association with another PZP(dimer) or
      PZP(dimer)-chymotrypsin complex in a very fast reaction that leads to the
      formation of 1:1 -chymotrypsin-PZP(tetramer) intermediate, probably with intact
      thiol esters. The interactions studied apparently are established early in the
      path of the reaction and the fluorescence changes probably reflect noncovalent
      enzyme-PZP contacts, which are not changed when covalent binding occurs. Further,
      fluorescence changes are seen only in reactions of PZP with enzymes, not with
      methylamine.

PMID- 1986801
TI  - Transplantation.

PMID- 1986800
TI  - Biophysical Journal thirty-fifth annual meeting. Program and abstracts. February
      24-28, 1991, San Francisco, California.

PMID- 1986802
TI  - Ethical implications of organ transplantation.

PMID- 1986803
TI  - Management of the organ donor: a first step in transplantation.

PMID- 1986804
TI  - Stress during the waiting period: a review of pretransplantation fears.

PMID- 1986805
TI  - Heart-lung transplantation: the patient with cystic fibrosis.

PMID- 1986806
TI  - Liver diseases that lead to transplantation.

PMID- 1986807
TI  - Renal transplantation: an option for end-stage renal disease patients.

PMID- 1986808
TI  - Restoration of sight by corneal transplantation.

PMID- 1986809
TI  - Organ donation from the family of a totally brain-dead donor: professional
      responsiveness.
AB  - Authoritative literature and clinically relevant data related to organ donation
      from a TBD family member lend support that organ donation is a multifaceted and
      challenging opportunity. These sources call forth multi-professional
      responsiveness in clinical practice, education, research, public policy, and
      ethics as advances in organ procurement and transplantation intensify. In turn,
      opportunities are rich for professionals to appreciate and to receive in new ways
      organ donation as a gift on behalf of society.

PMID- 1986810
TI  - The immune system: basic concepts for understanding transplantation.

PMID- 1986811
TI  - Kim Campbell's assurances to doctors about Bill C-43.

PMID- 1986812
TI  - Why won't doctors go where they are needed?

PMID- 1986813
TI  - The grass is always greener...

PMID- 1986814
TI  - A sample argument.

PMID- 1986815
TI  - Writing prescription instructions.

PMID- 1986816
TI  - Reducing the infant mortality rate.

PMID- 1986817
TI  - Why is screening mammography delayed?

PMID- 1986818
TI  - Electrical safety in patient care areas.

PMID- 1986819
TI  - What a loss!

PMID- 1986820
TI  - DNA sampling and informed consent.

PMID- 1986821
TI  - Health hazards from waste landfill.

PMID- 1986822
TI  - Report on amino acids.

PMID- 1986823
TI  - The gathering momentum against tobacco: action by physicians is needed on all
      fronts.

PMID- 1986824
TI  - Canadian physicians and tobacco.

PMID- 1986825
TI  - Surgery for epilepsy: summary of a consensus statement.

PMID- 1986826
TI  - Surgery for epilepsy: a new focus.

PMID- 1986827
TI  - Clinical uses of gonadotropin-releasing hormone analogues.
AB  - Gonadotropin-releasing hormone (Gn-RH) analogues are synthetic derivatives of the
      native hypothalamic peptide with alterations in their chemical structure that
      result in changes in biologic activity. Several Gn-RH agonists are available for
      clinical use, and all act through the same mechanism: first to stimulate and then
      to inhibit gonadotropin and gonadal steroid secretion by downregulating the
      pituitary Gn-RN receptors. This review should provide clinicians with a working
      knowledge of the physiologic and pharmacokinetic features of Gn-RH agonists.
      Although over 2000 articles concerning Gn-RH analogues have been published I
      chose to review only those that were the first to report a novel clinical
      application. Gn-RH agonists have proved to be extremely efficacious in treating
      gonadal steroid-dependent problems such as endometriosis, uterine leiomyoma,
      precocious puberty and prostate and breast cancers, and they have resulted in
      very few side effects. Long-term use may, however, lead to skeletal calcium loss
      in women as a consequence of hypoestrogenism. Further research is needed to
      prevent this and maintain clinical efficacy.

PMID- 1986828
TI  - Screening for hypercholesterolemia among Canadians: how much will it cost?
AB  - OBJECTIVE: To determine the cost of screening all Canadians aged 30 years or more
      without coronary heart disease (CHD) for hypercholesterolemia. DATA SOURCES: The
      expected results of initial screening of the serum cholesterol level were
      estimated on the basis of 1986 Canadian census data and the 1978 Canada Health
      Survey. The results of repeat testing were estimated on the basis of data from
      the Lipid Research Clinics Prevalence Study. Lipid profile results were
      extrapolated from tests at the Montreal General Hospital's clinical chemistry
      laboratory. Laboratory costs and primary care practitioner costs were provided by
      the Canadian Society of Clinical Chemists and provincial fee schedules
      respectively. MAIN RESULTS: Among 12,479,356 Canadians free of CHD 48.7% would be
      identified as being at high risk, 4.8% would be identified as being at moderate
      risk, and 46.6% would be reassured that their lipid risk for CHD was low. The
      total cost of implementing the program in the first year would be $432 million to
      $561 million ($325 million for laboratory tests and $107 million to $236 million
      for visits to primary care practitioners). CONCLUSION: The substantial cost of
      implementing a nationwide screening program must be weighed against the expected
      benefits to ensure that the final result is both practical and economically
      feasible.

PMID- 1986829
TI  - Cognitive and behavioural impairment among elderly people in institutions
      providing different levels of care.
AB  - OBJECTIVE: To compare the prevalence and degree of cognitive and behavioural
      impairment in elderly patients in institutions providing different levels of
      care. DESIGN: Prevalence study. SETTING: A nursing home, a home for the aged and
      psychogeriatric wards in a provincial psychiatric hospital. PATIENTS: Only
      subjects 65 years of age or older were eligible for inclusion. A random sample
      was selected comprising 25% of the residents in the nursing home and the home for
      the aged; of the 119 asked to participate 95 agreed (44 in the nursing home and
      51 in the home for the aged). All 50 on the psychogeriatric wards agreed to
      participate. MAIN OUTCOME MEASURES: The Mini-Mental State Examination (MMSE) and
      the Kingston Dementia Rating Scale (KDRS). RESULTS: An MMSE score of less than 24
      (cognitive impairment) was given to 37 (84%) of the residents in the nursing
      home, 43 (84%) of those in the home for the aged and 48 (96%) of the patients in
      the psychiatric hospital; the corresponding numbers for a KDRS score of more than
      0 (cognitive impairment) were 41 (93%), 48 (94%) and 50 (100%). The seven
      patients receiving the highest level of care at the home for the aged (special
      care) had more behavioural problems than those in the psychiatric hospital did (p
      less than 0.001). CONCLUSIONS: Cognitive and behavioural impairment was
      widespread in the three institutions regardless of the level of care. When
      planning services and allocating resources government funding agencies should
      consider the degree and prevalence of such impairment among elderly people in
      institutions.

PMID- 1986831
TI  - Lyme disease in Canada.

PMID- 1986830
TI  - Memory loss and pneumonitis after anaphylaxis due to an insect sting.

PMID- 1986832
TI  - Identification of the Lyme disease vector in Canada.

PMID- 1986834
TI  - Transfer of health care to natives holds much promise, lecturers say.

PMID- 1986833
TI  - Coffee, lipids and atherosclerosis.

PMID- 1986835
TI  - CMA's new director of health services continues clinical work with AIDS patients.

PMID- 1986836
TI  - Mandatory retirement ruling could have far-reaching implications for doctors.

PMID- 1986837
TI  - Good practice management can keep doctors out of court.

PMID- 1986838
TI  - Ayurvedism: eastern medicine moves west.

PMID- 1986839
TI  - Sexual abuse: Ottawa hospital tries to brush cobwebs from a murky, ill-defined
      world.

PMID- 1986840
TI  - Our drinking water: a cause for concern?

PMID- 1986841
TI  - With new Ottawa centre, acute care and health promotion share same address.

PMID- 1986842
TI  - American Cancer Society's second workshop on Methodology in Behavioral and
      Psychosocial Cancer Research. Santa Monica, California, December 5-8, 1989.
      Proceedings.

PMID- 1986843
TI  - Progress and challenges in psychosocial and behavioral research in cancer in the
      twentieth century.
AB  - Research in the psychosocial and behavioral aspects of cancer has shown steady
      growth since the 1950s, and its course of development has paralleled the history
      of medical techniques in treating cancer. Table 1 outlines this parallel
      evolution from the 1850s to the 1960s. The roles of the American Cancer Society
      and the National Cancer Institute (NCI) in spearheading and nurturing research in
      this area are documented. Interest in psychooncologic questions can be traced
      back for centuries to the search for etiologic factors and psychologic variables
      that would explain individual vulnerability to cancer. The first psychologic
      studies of cancer patients were reported in 1951 and 1952 from the Massachusetts
      General Hospital and Memorial Sloan-Kettering Cancer Center, respectively. The
      1970s saw new interest in psychosocial and behavioral research with many issues
      being addressed for the first time: better care of the terminally ill through
      more humanistic approaches including better means of pain control; ethical
      concerns related to patient rights and their status as subjects in experimental
      protocols; trying to measure quality of life for cancer patients on protocols;
      seeing the need for multidisciplinary collaborative groups to make up for the
      absence of formal training in this area; and the need to design valid, accurate
      measuring scales specific to the symptomology of patients with cancer. Table 4
      outlines how the 1980s gave increasing recognition and support to the
      psychosocial dimensions of cancer. This period produced a series of key
      conferences that examined a broad research and education perspective and produced
      recommendations that remain a benchmark in regard to instrumentation, conceptual
      models, pitfalls of psychosocial research, training, and education, and the
      organization of research efforts. New precision has been added to the field in
      the past 6 years: studies measuring concurrent psychologic, endocrine, and immune
      function; use of statistical modeling to incorporate quality of life data as a
      correction factor in survival data (TWiST and QALY); and broadened definitions of
      medical outcome to include functional status, thus allowing advances in
      psychiatric measurements to help answer questions in cancer. The challenges for
      the 1990s are identified in a summary in Table 9. Especially noteworthy is the
      observation that the comprehensive research needed today cannot be carried out by
      any one discipline alone. New approaches call for areas of the social sciences
      formerly inactive in cancer research (e.g., anthropology) to contribute the tools
      and expertise required to address the problems.

PMID- 1986844
TI  - Conceptualizing and measuring generic health outcomes.

PMID- 1986845
TI  - Advances in data assessment. Application to the etiology of nausea reported
      during chemotherapy, concerns about significance testing, and opportunities in
      clinical trials.
AB  - Typical inferential statistical procedures, such as the t-test and analysis of
      variance, compare differences in mean values of variables. This approach can
      sometimes obscure rather than illuminate research data. Here we present and
      discuss alternative data analytic techniques. Potential advantages of box plots
      over conventional t-tests for understanding data are shown by comparing the area
      under high and low frequencies from spectral curves of autonomic changes
      following chemotherapy treatment. Typical t-tests provide information regarding
      statistical significance in terms of the differences in group means; box plots
      and related exploratory techniques provide information regarding the
      characteristics of the distributions within the groups as well as examination of
      potential outliers. Multivariate analysis of variance (MANOVA) and other
      multivariate techniques are commonly used to deal with potentially complex data
      sets with multiple outcome measures. The potential advantages of visual
      clustering techniques such as star plots, Chernoff faces, and Andrew's Function
      Plots are demonstrated by examining changes in facial pallor caused by
      chemotherapy-induced nausea and vomiting. Typical MANOVA approaches can identify
      potential differences in mean values between groups; visual clustering approaches
      do this by graphically presenting complex interrelationships for individual
      cases. This approach enhances the visual interpretation of potential interactions
      that would be obscured by simply focusing on overall mean values. Preliminary
      data from a meta-analysis on the effect of metoclopramide on chemotherapy-induced
      vomiting demonstrates the potential uses and advantages of this summary technique
      over simple tabular summaries. We found significant relationships between the
      effect size of the drug and variables such as the year of study publication and
      whether the publication was an article or an abstract. While none of these
      techniques are meant to replace traditional inferential statistics, they offer
      advantages in terms of data exploration and understanding relationships within
      data sets that are not clearly addressed by other methods. They are potentially
      valuable alternatives worthy of exploration. Finally, we discuss issues of
      interim analyses and multiple endpoint assessment for clinical trials.

PMID- 1986846
TI  - Social environment and social support.
AB  - Research on the relevance of social support to cancer has been plentiful since
      the first American Cancer Society workshop on methodological issues in behavioral
      and psychosocial science. Nonetheless, critical shortcomings continue to
      characterize the attempt empirically to establish such things as the extent to
      which social support predicts adjustment to cancer diagnosis and treatment.
      Prominent among these is the failure to adequately address large elements of the
      social structure, such as social class and urbanization, and to investigate how
      they shape the well being of persons with or at risk for cancer and their
      caregivers. We recommend that more psychosocial research on the link between
      social support and cancer be conducted within populations beset by poverty and
      without adequate access to health care. Funding is needed for the training and
      maintenance of multidisciplinary and multicultural teams of researchers working
      within community-based organizations and hospitals serving the underserved.

PMID- 1986847
TI  - Social support and the cancer patient. Implications for future research and
      clinical care.
AB  - This review assesses past progress, current practices, and future needs in
      research and clinical practice involving the social support needs of cancer
      patients. A review is given of the various conceptualizations of the social
      support/stress paradigm and of the state of the art of measuring social support.
      Then the current work in the field of social support and cancer is considered and
      an argument is made for the use of social support measures, which are relevant to
      the experiences of the cancer patient. Potential adaptations of an existing
      instrument (the Duke-UNC Functional Social Support Scale) are demonstrated, and a
      taxonomy of stages of cancer that would require additional types of social
      support measures and interventions is outlined. Interventions are discussed in
      terms of the traditional support groups as well as interventions by the
      oncologist and primary care physician. An argument is made for the inclusion of
      quality of life or functional measures as outcomes in clinical trials and the
      care of the cancer patient. Finally, the need to address the existential,
      philosophic, or religious issues surrounding cancer and its treatment is
      discussed.

PMID- 1986848
TI  - Needs and recommendations for behavior research in the prevention and early
      detection of cancer.
AB  - Because life-style patterns affect many cancer risks, research on health-risk
      behavior and behavior change is critical to cancer prevention. This report
      recommends priorities for the next decade of psychosocial research on cancer
      prevention and detection. The leading priority for future research is to fill
      gaps in basic knowledge left by the rush to intervention and outcome studies.
      Such research must be theoretically driven and should aim to develop broad
      principles applicable to diverse health behaviors. Studies that include relevant
      process data on various stages of behavior change are considered more desirable
      than simple outcome studies. Epidemiologic investigations should be expanded to
      include measures of relevant behaviors, so that their impact on clinical outcomes
      might be established. More research is needed on lay perception of health risks
      and on individual and health-system barriers to effective cancer prevention and
      detection. Studies that address the needs of minority and underprivileged
      populations are crucial. Funding agencies' narrow categorical mandates impede
      interdisciplinary research on multiple risk factors and their interactions; these
      boundaries must be relaxed to promote such approaches. Funding agencies should
      also consider basic research as a long-term investment towards the development of
      effective interventions.

PMID- 1986849
TI  - Assessing how people change.
AB  - Traditional assessments of behavior change relied on discrete measures based on
      assumptions that changes occur quickly, dichotomously, and without relapse.
      People were expected to shift dramatically from smokers to nonsmokers or from
      unhealthy to healthy lifestyles. A stage model of change has greater potential to
      assess the dynamics of change with some people progressing linearly from
      contemplation to maintenance, others relapsing back to contemplation, and others
      remaining in a stage like contemplation for long periods. Stage measures provide
      differential predictions for the amount of progress people in different stages
      will make after treatment. Assessing processes of change that people apply to
      progress from one stage to the next can also help to explain the dynamics of
      behavior change.

PMID- 1986850
TI  - Epidemiologic perspectives on life-style modification and health promotion in
      cancer research.
AB  - The clinical, patient-oriented focus of medicine and psychology is contrasted
      with the epidemiologic (public health) approach in assessing the role of life
      style factors and health promotion in cancer research. The unifying host-agent
      environment epidemiologic paradigm is applied to contemporary cancer prevention
      issues, principally smoking cessation and dietary modification, to demonstrate
      differences in inferences, prevention strategies, and research opportunities. An
      integration of population-based approaches with the dynamics of patient behavior
      and risks for cancer is especially salient when considering the role of
      psychosocial stress and personal and social resources. The social epidemiologic
      perspective, the study of the psychosocial determinants of physical health
      status, offers one approach for resolving the outlined differences in
      perspectives and is particularly relevant for understanding the etiology of life
      style behaviors and how they might be altered.

PMID- 1986851
TI  - Physiologic and psychobehavioral research in oncology.
AB  - A major thrust in research in psychosocial oncology is the study of the
      interaction of psychologic and physiologic variables. This discussion reviews the
      current status and future directions of such research. Areas addressed include
      pain, nausea and vomiting with chemotherapy, sexuality, effects of cancer on
      psychologic and neuropsychologic function, impact of psychologic factors on
      cancer and its treatment, and psychoneuroimmunology. In addition, specific
      recommendations for strategies to facilitate research in these areas of
      psychosocial oncology are proposed.

PMID- 1986852
TI  - Research in cancer pain. What we know and what we need to know.

PMID- 1986853
TI  - Psychoneuroimmunology. Implications for oncology?
AB  - Accumulating evidence indicates that the central nervous system (CNS) may
      regulate the activity of the immune system. Although the overall significance of
      the immune system in cancer remains controversial, psychosocial influences on
      immune function could potentially provide a mechanism to account for some of the
      reports of an association between psychosocial factors and cancer prognosis.

PMID- 1986854
TI  - Scientific inquiry in childhood cancer psychosocial research. Theoretical,
      conceptual, and methodologic issues in the investigation and behavioral treatment
      of procedure-related distress.
AB  - This paper discusses the current status of scientific inquiry in childhood cancer
      psychosocial research. The investigation and behavioral treatment of procedure
      related distress serves as a model for illustrating and outlining some of the
      theoretical, conceptual, and methodologic issues and problems that exist in the
      area of childhood cancer psychosocial research. Specifically, issues related to
      the process of scientific inquiry, theoretical/conceptual modeling, measurement
      and assessment, and behavioral treatment strategies are discussed. Examples of
      how these issues have been addressed in our investigations of procedure-related
      distress are presented and recommendations for facilitating growth and
      development in the field of childhood cancer psychosocial research are offered.

PMID- 1986855
TI  - Quality of life research in oncology. Past achievements and future priorities.
AB  - The status of quality of life research in oncology is assessed, and priorities
      for future research with regard to conceptual and theoretical developments, focus
      and content of research, research designs and practical strategies for research
      implementation, and transferring information to clinical practice and medical
      policy decision-making are identified. There is general agreement that quality of
      life is a subjective and multidimensional construct, yet comprehensive
      theoretical models have not been developed and applied fully. We recommend that
      future research be based on conceptual models that explicate the
      interrelationships among quality of life domains throughout the stages of cancer
      care. These models, and the longitudinal research that follows from them, should
      attend specifically to cross-class and cross-cultural issues to avoid
      overgeneralization from theory and research that are based largely on the views
      of the majority culture. We encourage the inclusion of this theory-based quality
      of life assessment as a standard component of clinical trials. Success in this
      endeavor will require additional standardization of quality of life measures for
      use across a range of cancer patient populations, including the development of
      age-specific norms and instruments designed to assess the entire family system.

PMID- 1986856
TI  - Methodologic issues in assessing the quality of life of cancer patients.
AB  - Although quality of life assessments have been employed successfully in
      descriptive and evaluative studies in oncology, their use in cancer clinical
      trials has, to date, been limited. A range of issues have impeded the conduct of
      clinical trial-based quality of life investigations. These include: the absence
      of theoretical models to guide the development of quality of life measures; over
      reliance on ad hoc approaches to quality of life assessment; and insufficient
      attention to the practical constraints operating in clinical research settings.
      Of primary importance is the need to develop multidimensional quality of life
      instruments that are brief and psychometrically robust. It is suggested that
      future work on instrument development focus on refining currently available
      generic or cancer-specific measures, and on developing new diagnostic-specific
      questionnaire modules. This psychometric work should be guided by appropriate
      theoretical models of the relationship among health-related quality of life
      domains. Although it is widely accepted that the patient represents the most
      appropriate source of quality of life data, it is suggested that efforts also be
      directed toward improving the validity and reliability of physician-generated
      assessments of patients' performance status and of treatment toxicities, and
      toward determining the feasibility of employing family members as proxy raters of
      the psychologic and social health status of patients who are unwilling or unable
      to provide such information. Additional attention should be paid to the many
      logistical problems that arise in clinical trial-based quality of life
      investigations. In particular, research designs and data collection procedures
      should be selected that minimize patient, medical staff, and institutional
      burden.

PMID- 1986857
TI  - Quality-of-life-adjusted survival for comparing cancer treatments. A commentary
      on TWiST and Q-TWiST.
AB  - In chronic disease situations where treatment comparisons favor no particular
      therapy, or where definitive outcome requires a considerable follow-up period, it
      is useful to have additional and perhaps intermediate endpoints of relevant
      clinical significance to compare treatments. One such endpoint is Time Without
      Symptoms and Toxicity (TWiST) which, together with Q-TWiST, attempts to address
      the quality of life of patients receiving the competing regimens. This paper
      provides a commentary on these techniques with an emphasis on the problems
      inherent in implementing Q-TWiST, a measure that attempts to incorporate patient
      value preferences into TWiST. It is argued that while Q-TWiST is intuitively
      appealing in the clinical setting, there are formidable design and psychometric
      hurdles that must be overcome to fully operationalize the concept.

PMID- 1986858
TI  - Quality of life after cancer. A policy perspective.

PMID- 1986859
TI  - Progress in psychosocial and behavioral cancer research. The need for enabling
      strategies.
AB  - A major component of the Second Workshop on Methodology in Behavioral and
      Psychosocial Cancer Research was a discussion of enabling strategies, that is,
      strategies by which future goals and needs in the area of psychosocial and
      behavioral oncology might be accomplished. This report describes and comments on
      the discussion that took place at a special plenary session at which
      representatives from four funding agencies, the American Cancer Society, National
      Cancer Institute, National Institute of Mental Health, and National Science
      Foundation, presented their views and their agencies' programs for promoting
      research in psychosocial and behavioral oncology. It is concluded that much
      progress has been made in the field and that strategies are in place for ensuring
      continued progress. However, suggestions are also made for new strategies that
      might accelerate and broaden that progress.

PMID- 1986860
TI  - Behavioral and psychosocial cancer research. Building on the past, preparing for
      the future.
AB  - This report identifies five general conclusions that emerged from the Second
      Workshop on Methodology in Behavioral and Psychosocial Cancer Research. These
      conclusions address diverse topics, including a focus on areas other than
      methodology; an emphasis on the transfer of technology and knowledge to applied
      settings; a recognition of the role of basic behavioral research in answering
      clinical questions; the need to recognize and strengthen ties between the field
      of behavioral and psychosocial oncology and the basic behavioral and social
      science fields from which it emerged; and the importance of additional research
      on minorities and other special populations. It is suggested that meeting the
      challenges posed in each of these five areas is critical to continued progress in
      the field.

PMID- 1986861
TI  - Sex, maps, and imprinting.

PMID- 1986863
TI  - Naming a targeting signal.

PMID- 1986862
TI  - Network antibodies identify nuclear lamin B as a physiological attachment site
      for peripherin intermediate filaments.
AB  - We studied the molecular associations between peripherin (a neuronal, type III
      intermediate filament subunit) and nuclear lamins. We show here that isolated
      peripherin binds selectively to mammalian lamin B under in vitro conditions. We
      further demonstrate that a synthetic peptide, representing the proximal part of
      peripherin's tail domain (P1), also associates with mammalian lamin B in a
      saturable, cooperative, and specific fashion. Laboratory animals immunized with
      P1 spontaneously develop idiotypic and anti-idiotypic antibodies recognizing
      peripherin and lamin B, respectively. These data provide essentially in vivo
      evidence that lamin B represents a constitutive nuclear "receptor" site for the
      tail domains of peripherin intermediate filaments.

PMID- 1986864
TI  - The recombination activating gene-1 (RAG-1) transcript is present in the murine
      central nervous system.
AB  - The recombination activating genes, RAG-1 and RAG-2, are likely to encode
      components of the V(D)J site-specific recombination machinery. We report here the
      detection of low levels of the RAG-1 transcript in the murine central nervous
      system by polymerase chain reaction, in situ hybridization, and Northern blot
      analyses. In contrast, an authentic RAG-2 transcript could not be detected
      reproducibly in the central nervous system. The RAG-1 transcript was found to be
      widespread in embryonic and postnatal neurons, with transcription being most
      apparent in regions of the postnatal brain with a high neuronal cell density (the
      cerebellum and the hippocampal formation). The results suggest that RAG-1
      functions in neurons, where its role might be to recombine elements of the
      neuronal genome site-specifically, or to prevent detrimental alterations of the
      genome in these long-lived cells.

PMID- 1986865
TI  - Conjugational recombination in E. coli: myths and mechanisms.

PMID- 1986866
TI  - Selective expression of RAG-2 in chicken B cells undergoing immunoglobulin gene
      conversion.
AB  - Chickens create their immunoglobulin (Ig) repertoires during B cell development
      in the bursa of Fabricius by intrachromosomal gene conversion. Recent evidence
      has suggested that Ig gene conversion may involve cis-acting DNA elements related
      to those involved in V(D)J recombination. Therefore, we have examined the
      potential role of the V(D)J recombination activating genes, RAG-1 and RAG-2, in
      regulating chicken Ig gene conversion. In contrast to the coexpression of RAG-1
      and RAG-2 observed in mammalian B cells that undergo V(D)J recombination, chicken
      B cells isolated from the bursa of Fabricius express high levels of the RAG-2
      mRNA but do not express RAG-1 mRNA. The developmental and phenotypic
      characteristics of the bursal lymphocytes and chicken B cell lines that express
      RAG-2 mRNA demonstrate that selective RAG-2 expression occurs specifically in B
      cells undergoing Ig diversification by gene conversion. These data suggest that
      RAG-2 plays a fundamental role in Ig-specific gene conversion.

PMID- 1986867
TI  - PDGF A-chain gene is expressed by mammalian neurons during development and in
      maturity.
AB  - Platelet-derived growth factor (PDGF) may be a critical factor in the temporal
      differentiation of glial elements in the mammalian central nervous system. We
      have used in situ hybridization and immunoperoxidase staining to investigate the
      localization of PDGF A and have observed high levels of PDGF A-chain mRNA and
      immunoreactive PDGF A in neurons of embryonic and adult mice. PDGF A-chain
      expression was shown to be developmentally regulated and tissue specific. Every
      neuronal population examined in the central and peripheral nervous systems
      expresses PDGF A transcripts. Variable, significantly weaker signals are observed
      in glial cells. In contrast to known neurotrophic factors, the PDGF A transcripts
      are widely distributed among neurons. This generalized distribution of PDGF A
      transcripts, together with the known effects of PDGF on glial cells in vitro,
      suggests a unique role of neurons in regulating the proliferation and
      differentiation of glial cells in vivo.

PMID- 1986868
TI  - PDGF B-chain in neurons of the central nervous system, posterior pituitary, and
      in a transgenic model.
AB  - Platelet-derived growth factors (PDGFs) are growth-regulatory molecules that
      stimulate chemotaxis, proliferation, and increased metabolism of primarily
      connective tissue cells. In a survey of normal tissues, we found specific
      immunostaining for PDGF B-chain in neurons, principal dendrites, some axons, and
      probable terminals throughout the brain, in the dorsal horn of the spinal cord,
      and in the posterior pituitary of a nonhuman primate (Macaca nemestrina). PDGF
      activity was extracted from brain cortex and posterior pituitary, and ubiquitous
      expression of transcripts for the two chains of PDGF and both PDGF receptors was
      detected throughout the brain and posterior pituitary. A transgenic model was
      also evaluated in which the chloramphenicol acetyltransferase gene was placed
      under transcriptional control of the PDGF B-chain promoter. The transgene was
      preferentially expressed within neural cell bodies in the cortex, hippocampus,
      and cerebellum. PDGF may act as a neuronal regulatory agent. Neuronal release of
      PDGF could contribute to nerve regeneration and to glial proliferation that leads
      to gliosis and scarring.

PMID- 1986869
TI  - The Drosophila maternal-effect gene fs(1)Ya encodes a cell cycle-dependent
      nuclear envelope component required for embryonic mitosis.
AB  - The maternal-effect gene fs(1)Ya is specifically required for embryonic mitosis
      in Drosophila. fs(1)Ya is involved in the initiation of the first embryonic
      mitosis and may also be necessary for subsequent embryonic mitotic divisions.
      fs(1)Ya encodes a 91.3 kd hydrophilic protein containing two putative MPF
      phosphorylation target sites and two potential nuclear localization signals. This
      protein is synthesized during postoogenic maturation from its maternal RNA and
      persists throughout embryogenesis. In early embryos, the fs(1)Ya protein is
      localized to the nuclear envelope from interphase to metaphase. During anaphase
      and telophase, it is dispersed in the nucleoplasm and cytoplasm, a behavior that
      is different from that of both the nuclear envelope and lamins. These results
      suggest that the fs(1)Ya protein is a cell cycle-dependent component of the
      nuclear envelope that specifically functions in embryonic mitosis.

PMID- 1986870
TI  - Protein traffic between distinct plasma membrane domains: isolation and
      characterization of vesicular carriers involved in transcytosis.
AB  - We have isolated a population of vesicular carriers involved in the transport
      (transcytosis) of proteins from the basolateral to the apical plasma membrane of
      hepatocytes. The obtained fraction was enriched in compartments containing known
      transcytosed proteins and depleted in elements of the secretory pathway, Golgi
      elements, basolateral plasma membrane, as well as early endosomal components. The
      fraction was analyzed by biochemical and immunological procedures. Antibodies
      raised against the proteins in the fraction recognized a single 108K antigen.
      Based on its subcellular distribution, the 108K antigen may represent a novel
      marker for transcytotic vesicular carriers.

PMID- 1986871
TI  - Identification of an autocrine negative growth factor: mouse beta-galactoside
      binding protein is a cytostatic factor and cell growth regulator.
AB  - Murine beta-galactoside-binding protein, a protein classified as a soluble
      lectin, is shown to be a cell growth-regulatory molecule and a cytostatic factor.
      The growth-inhibitory effect is not related to lectin properties, and competition
      assays indicate that the protein binds to specific cell surface receptors with
      high affinity. It exerts control in G0 and at G2, both as a regulator of cell
      replication and as a cytostatic factor.

PMID- 1986872
TI  - Evaluation of performance characteristics of disposable bag-valve resuscitators.
AB  - OBJECTIVE: To evaluate the performance characteristics of disposable bag-valve
      resuscitators. DESIGN: Single and multitrial tests under simulated clinical
      conditions. Results of multitrial tests were analyzed by multivariate analysis of
      variance. SETTING: A pulmonary laboratory in a university hospital. METHODS: We
      evaluated eight DRs to determine: a) physical characteristics, including the
      potential for misassembly; b) FIO2 of 1.0 and flow rates of 10 L; c) tidal volume
      (VT) (male and female operators) using one and two hands; and d) cycling rates at
      5 degrees, 20 degrees, and 48 degrees C. RESULTS: All resuscitators met the
      minimum requirements of the Canadian Standards Association and the American
      Society for Testing and Materials. However, the CPR and LSP could be assembled
      incorrectly for use. Three units (B Sav, Pulm, and MPR) delivered significantly
      less than 80% oxygen (overall p less than .05). Significant increases were seen
      in VT using two hands vs. one hand (1176 vs. 960 mL, p less than .001) and males
      vs. females using two hands (1284 vs. 1102 mL, p less than .02). One unit (B Sav)
      could only be used with two hands. The maximum cycling rates for all units
      increased significantly (p less than .05) with an increase in temperature from -5
      degrees to 20 degrees to 40 degrees C. However, two units (Bag E and MPR) failed
      to deliver 20 breaths/min at -5 degrees C, while the B Sav and Pulm valves became
      dysfunctional at 48 degrees C. CONCLUSIONS: While these DRs meet the minimum
      standards, they should be chosen carefully and evaluated before application in
      the clinical environment.

PMID- 1986873
TI  - Predicting short-term outcome of cardiopulmonary resuscitation using central
      venous oxygen tension measurements.

PMID- 1986874
TI  - Digital ischemia complicating pneumococcal sepsis: reversal with sympathetic
      blockade.

PMID- 1986876
TI  - Life-threatening complications from percutaneous dilational tracheostomy.

PMID- 1986875
TI  - Atenolol-induced cardiovascular collapse treated with hemodialysis.

PMID- 1986878
TI  - Resolution of lactic acidosis after sedation of a patient with acute myocardial
      infarction and left ventricular failure.

PMID- 1986877
TI  - Pediatric critical care cost containment: combined actuarial and clinical
      program.
AB  - OBJECTIVE: To determine if providing patients' daily survival probabilities to
      physicians and nurses along with a short videotape on the measurement of survival
      probabilities and costs of pediatric intensive care would reduce resource use.
      DESIGN: Prospective, randomized, controlled trial. SETTING: Pediatric ICU.
      PATIENTS: Medical patients in a prospective control period (n = 113), an
      intervention period (n = 226), and a follow-up control period (n = 97).
      INTERVENTIONS: The survival probabilities of 50% of the patients in the
      intervention period were displayed at the bedside and the staff viewed a short
      videotape on the measurement of survival probabilities and costs of pediatric
      intensive care. MEASUREMENTS AND MAIN RESULTS: Daily survival probabilities and
      resource use were evaluated each day. Resource use, adjusted for severity of
      illness, was evaluated using analysis of covariance. Compared with the
      prospective control group, reductions in the daily use of blood gases (p less
      than .01), hematology tests (p less than .001), hourly vital signs (p less than
      .001), and hourly neurologic vital signs (p less than .001) resulting in a
      composite reduction in daily laboratory and imaging charges from $759 +/- $22 to
      $622 +/- $18 (p less than .01) were observed in the patient group receiving the
      survival probabilities and whose physicians also viewed the videotape. Equivalent
      reductions in resource use also occurred in a simultaneous control group
      (patients did not receive survival probabilities but healthcare workers did view
      the videotape) and in a follow-up control group. CONCLUSION: Reduction in
      pediatric intensive care resource use can occur from the combined effects of
      actuarial and clinical interventions.

PMID- 1986879
TI  - Toxic shock syndrome following influenza A in a child.

PMID- 1986880
TI  - Passive leg raising.

PMID- 1986882
TI  - Spectrum analysis of heart rate variations as a marker of spinal cord damage.

PMID- 1986881
TI  - Use of survivors' cardiorespiratory values as therapeutic goals in septic shock.

PMID- 1986883
TI  - Bilious pleural effusion as a complication of attempted percutaneous biliary
      drainage.

PMID- 1986884
TI  - Anion gap: low sensitivity or erroneous reference range?

PMID- 1986885
TI  - High costs associated with prolonged labetalol infusions.

PMID- 1986886
TI  - Increased extravascular lung water in patients with low pulmonary artery
      occlusion pressure after acute myocardial infarction.
AB  - OBJECTIVE: To evaluate the clinical characteristics of increased extravascular
      lung water (EVLW) in patients with low pulmonary artery occlusion pressure (PAOP)
      in the early phase of acute myocardial infarction. DESIGN: Consecutive sample for
      descriptions of the clinical features of medical disorders. SETTING: A general
      medicine group practice in a university hospital. PATIENTS: Sixteen patients with
      low PAOP (less than 18 mm Hg) on the initial measurement obtained within 12 hr of
      chest pain onset. MEASUREMENTS AND MAIN RESULTS: EVLW was measured by the thermal
      indocyanine green dye double-indicator dilution method. QRS score was obtained on
      hospital day 7 from the Selvester's QRS Scoring System. Eleven (69%) patients had
      increased EVLW greater than 7 mL/kg despite low PAOP. EVLW had no significant
      correlation with PAOP and the difference between plasma colloid osmotic pressure
      and PAOP, but did have a significant correlation with pulmonary vascular
      resistance index (r2 = .31, p less than .05), and QRS score (r2 = .45, p less
      than .005). CONCLUSIONS: Larger infarcts led to increased EVLW even with low
      PAOP, and the accumulation of increased EVLW around the small arterioles might
      have led to increased pulmonary vascular resistance.

PMID- 1986887
TI  - Breathing circuit respiratory work in infants recovering from respiratory
      failure.
AB  - OBJECTIVE: To compare cardiopulmonary function during spontaneous breathing with
      three continuous-flow breathing circuits. The major difference between these
      circuits was the degree of flow resistance offered by the exhalation valve.
      DESIGN: Randomized crossover trial. PATIENTS: Twelve infants less than 12 months
      of age recovering from respiratory failure of variable etiology. Only patients
      weighing 3 to 10 kg were studied. INTERVENTIONS: The patients were connected to
      each respiratory circuit in a random sequence, with 15 min allowed for
      equilibration before assessment of cardiopulmonary function. Airway pressure
      (Paw) and FIO2 were maintained unchanged. MEASUREMENTS AND MAIN RESULTS:
      Ventilation, gas exchange, or circulatory function were not altered significantly
      by changing the breathing circuit. However, Paw and esophageal pressure
      fluctuations were altered and were largest during breathing with the circuit that
      had an exhalation valve with high-flow resistance. The Paw fluctuation recorded
      while the patient was breathing with the flow-resistor circuit increased with
      weight and exceeded 2 cm H2O in all patients weighing greater than 4.5 kg. Paw
      fluctuation could be decreased by greater than 2 cm H2O in ten of 12 patients by
      using the threshold-resistor circuit. CONCLUSIONS: The results indicate a need
      for evaluating the characteristics of respiratory circuits used for spontaneous
      breathing in infants and children, to avoid unnecessary equipment-related
      increase in respiratory work.

PMID- 1986888
TI  - Evolution of energy expenditure and nitrogen excretion in severe head-injured
      patients.
AB  - OBJECTIVE: The aim of the study was to estimate the influence of therapeutic
      changes on the level of energy expenditure (EE) and N excretion in a homogeneous
      group of patients usually considered hypermetabolic. DESIGN: EE and N excretion
      of head-injured patients were measured simultaneously at phases 1 and 2 (patients
      treated 4 +/- 3 and 18 +/- 8 days after injury, respectively). SETTING: Acute
      care hospital. PATIENTS: Eight severe head-injured patients, mean weight 63.1 +/-
      6.1 (SD) kg, mean age 21 +/- 3.8 (SD) yr. INTERVENTIONS: At phase 1, all patients
      were sedated with fentanyl (6.7 +/- 1.9 micrograms/kg.hr) plus flunitrazepam (9.1
      +/- 4.8 micrograms/kg.hr) and were mechanically ventilated. All patients received
      continuous total parenteral nutrition. The nonprotein caloric intake averaged
      1092 +/- 200 kcal/day, including 77% glucose and 23% fat (Intralipid 20%). The
      total N intake averaged 7 +/- 5 g/day, consisting of crystalline amino acids. At
      phase 2, no patient received any sedative and all were breathing spontaneously
      via tracheostomy. All patients received parenteral and/or enteral nutrition. The
      nonprotein caloric intake averaged 1929 +/- 200 kcal/day consisting of 65%
      carbohydrates and 35% fat. The total N intake averaged 13 +/- 2 g/day.
      MEASUREMENTS AND MAIN RESULTS: The EE was significantly higher at phase 2 than at
      phase 1 (2121 vs. 1737 kcal), but the interindividual variability was low at both
      phases. N excretion was high at the two periods of the study and not correlated
      to the level of EE. The RQ was 0.75 at both periods, indicating predominant fat
      oxidation. CONCLUSIONS: We could not demonstrate any parallelism in the evolution
      of EE and protein catabolism in head-injured patients. The therapeutics
      (mechanical ventilation, sedation, and nutrition) have a major effect on EE but
      little on N excretion.

PMID- 1986889
TI  - Measurement of minute ventilation in ventilator-dependent patients: need for
      standardization.
AB  - OBJECTIVES: a) To determine the variation in methods used to measure minute
      ventilation (VE) in patients who receive mechanical ventilation; b) to determine
      the effect of supplemental oxygen on VE, respiratory rate (RR), and tidal volume
      (VT) measurements. DESIGN: Telephone survey of hospitals, and a randomized
      control trial. SETTING: Medical and surgical ICUs in a university hospital.
      PATIENTS: Thirty-three patients who had required mechanical ventilation because
      of the inability to sustain adequate spontaneous ventilation. All patients were
      considered ready to undergo a weaning trial by their physicians. INTERVENTIONS:
      Spontaneous VE, RR, VT, and SaO2 were measured both in the presence and absence
      of supplemental oxygen; measurements were obtained in a randomized manner.
      MEASUREMENTS AND MAIN RESULTS: a) In a telephone survey of hospitals throughout
      the country, we found that the measurement of VE is variably obtained during room
      air breathing or in the presence of supplemental oxygen. b) Measurements of VE
      increased from 11.0 +/- 0.8 L/min while patients received supplemental oxygen to
      13.5 +/- 1.1 L/min while patients breathed room air (p less than .001). Of 15
      patients who had a VE less than 10 L/min while receiving supplemental oxygen,
      seven developed a value greater than 10 L/min while breathing room air; thus, a
      weaning trial might have been inappropriately deferred in these patients. c) Mean
      SaO2 decreased from 95.0 +/- 0.6% while breathing supplemental oxygen to 90.2 +/-
      1.1% while breathing room air (p less than .001). CONCLUSIONS: Measurements of VE
      in patients being considered for a weaning trial can result in significant oxygen
      desaturation if obtained during room air breathing, and the values obtained can
      significantly overestimate the patient's true ventilatory requirements, since
      most patients receive supplemental oxygen during a weaning trial. Standardized
      methods of measuring VE in critically ill patients need to be developed.

PMID- 1986890
TI  - Surviving long-term dialysis.

PMID- 1986891
TI  - Hemodynamic profiles of prostaglandin E1, isoproterenol, prostacyclin, and
      nifedipine in experimental porcine pulmonary hypertension.
AB  - BACKGROUND AND METHODS: We compared the hemodynamic effects of four vasodilators
      in experimental embolic pulmonary hypertension in a randomized controlled trial,
      using nine pigs weighing 16 to 23 kg. After anesthesia induction and cannulation
      with arterial, central venous, and thermodilution output pulmonary artery
      catheters, animals were repetitively embolized with glass beads (60 to 160 mu) in
      order to establish pulmonary hypertension (pulmonary artery pressure [PAP]
      doubled from baseline). Prostaglandin E1 (PGE1), isoproterenol, prostacyclin
      (PGI2), and nifedipine were compared at doses producing equivalent reduction in
      systemic BP. RESULTS: Only PGE1 and PGI2 decreased both PAP and pulmonary
      vascular resistance (PVR). PGE1 decreased PAP from 39 +/- 1 to 33 +/- 1 mm Hg;
      prostacyclin decreased PAP from 38 +/- 1 to 31 +/- 1 mm Hg and produced the
      largest increase in cardiac output (Qt). Isoproterenol did not change PAP,
      markedly increased heart rate (162 +/- 8 to 216 +/- 11 beats/min), and resulted
      in significant arrhythmias. Nifedipine increased PVR from 1044 +/- 113 to 1125 +/
      100 dyne.sec.cm-5 and decreased Qt. CONCLUSIONS: Vasodilators demonstrate unique
      hemodynamic drug profiles. Isoproterenol infusion is characterized by tachycardia
      and arrhythmias. Both PGE1 and PGI2 effectively decrease PAP and PVR. Nifedipine
      depressed Qt significantly in this glass-bead embolization model of acute
      pulmonary hypertension.

PMID- 1986892
TI  - Effects of milrinone on pulmonary vasculature in normal dogs and in dogs with
      pulmonary hypertension.
AB  - OBJECTIVE: To study the effects of milrinone on pulmonary vasculature.
      BACKGROUND: It has been suggested that bipyridines or their derivatives may have
      a selective pulmonary vasodilation effect. METHODS: Preliminary study: milrinone
      administration to 12 normal dogs (low dose [bolus 75 micrograms/kg for 5 min
      followed by a continuous infusion at 0.75 micrograms/kg.min, n = 6]; high dose
      [bolus 150 micrograms/kg for 5 min followed by continuous infusion at 1.5
      micrograms/kg.min, n = 6]). Main study: milrinone administration to 18 dogs with
      pulmonary hypertension due to pulmonary embolism induced by a massive injection
      of autologous muscle cubes. The pulmonary hypertension dogs were divided into
      three groups: a) group E (n = 6) received embolization only, as control; b) group
      L (n = 6) received low-dose milrinone; and c) group H (n = 6) received high-dose
      milrinone, equivalent to the preliminary study group. Hemodynamic measurements
      and blood samplings were obtained at baseline and at 15, 30, and 60 min after
      start of milrinone infusion. RESULTS: Milrinone did not change mean pulmonary
      artery pressure (MPAP) in normal dogs. Milrinone decreased MPAP significantly in
      dogs with pulmonary hypertension. Pulmonary vascular resistance index remained at
      an almost constant level in normal dogs, but decreased significantly in dogs with
      pulmonary hypertension. Mean arterial pressure was maintained at a constant level
      in all groups. High-dose milrinone administration decreased systemic vascular
      resistance index (SVRI) significantly; low-dose milrinone administration
      decreased SVRI slightly. CONCLUSIONS: Milrinone may have a selective pulmonary
      vasodilatory effect only in dogs with pulmonary hypertension. The mechanism that
      produced a selectivity on pulmonary vasculature in dogs with pulmonary
      hypertension is unknown. However, an inhibition of platelet aggregation may
      decrease the MPAP resulting from an increase in cAMP caused by milrinone. Further
      studies are needed to resolve the pulmonary vasodilatory effect of milrinone in
      dogs with pulmonary hypertension.

PMID- 1986893
TI  - Fructose-1,6-bisphosphate, when given immediately before reoxygenation, or before
      injury, does not ameliorate hypoxic ischemic injury to the central nervous system
      in the newborn pig.
AB  - BACKGROUND AND METHODS: We demonstrated earlier in our laboratories that fructose
      1,6-bisphosphate (FDP) would improve the outcome of hypoxic ischemic injury to
      the brain in the adult rabbit. Since many human newborns suffer hypoxic injury to
      the brain, with a secondary ischemic component due to hypoxic cardiac failure, we
      set out to reproduce similar experiments in newborn piglets. Hypoxic ischemic CNS
      damage was induced by ligating both carotid arteries and reducing BP to 66% of
      normal for 30 min; in the last 15 min, FIO2 was reduced to 0.6. Twelve piglets
      were randomized to receive either 175 mg/kg of FDP in the last 5 min before
      reoxygenation or the equivalent volume of saline. The other 20 piglets received
      75 mg/kg of FDP in the 5 min immediately before carotid ligation, followed by 1.8
      mg/kg.min continuous infusion for the 30 min of hypoxia and ischemia or an
      equivalent volume of saline. RESULTS: There were no significant differences in
      the neurologic exam scores or pathologic exam scores between the FDP and control
      animals at either dose level. CONCLUSIONS: In this animal model, FDP at the doses
      given was not effective in ameliorating hypoxic ischemic injury to the CNS.

PMID- 1986894
TI  - Acute renal failure in critically ill patients: prognosis for recovery of kidney
      function after prolonged dialysis support.
AB  - OBJECTIVE: To clarify the prognosis for eventual recovery of kidney function in
      patients who experience prolonged dialysis dependence after acute renal failure
      (ARF). DESIGN: Retrospective, chart review. SETTING: Inpatients of a large,
      referral-based hospital. PATIENTS: Twenty-six consecutive survivors of ARF who
      required greater than 4 wk of dialysis support. RESULTS: All 26 patients were
      critically ill and developed ARF during treatment in an ICU. The clinical course
      of these patients was characterized by multiple episodes of renal ischemia or
      nephrotoxin exposure during dialysis dependence. However, despite multiple renal
      insults and prolonged dialysis support (mean duration 8.4 +/- 0.7 wk), 23 (88%)
      of the 26 patients recovered sufficient kidney function to discontinue dialysis.
      Preexisting renal impairment was associated with a greater risk of irreversible
      renal failure, and, in patients able to discontinue dialysis, renal recovery was
      often incomplete. CONCLUSIONS: Despite some renal damage, most critically ill
      patients who survive ARF requiring prolonged dialysis support recover life
      sustaining kidney function.

PMID- 1986896
TI  - Noninvasive cerebral optical spectroscopy for monitoring cerebral oxygen delivery
      and hemodynamics.
AB  - OBJECTIVE: To present an algorithm for noninvasive measurement of cerebral oxygen
      saturation (cerebral oximetry) and cerebral hemodynamics with near infrared
      spectroscopy. DESIGN: In vitro correlation of oximetry measurements with
      reference measurements; illustrative cases of hemodynamic and oximetric
      recordings. SETTING: Tertiary care neuroscience ICU. PATIENTS: Brain-injured
      patients with a prolonged, decreased level of consciousness chosen as
      illustrative examples. INTERVENTIONS: Two-channel multiple wavelength diffuse
      infrared transmission spectroscopy was interfaced with the scalp using adhesive.
      Transmission data were collected with gross superficial-to-deep spatial
      resolution. Saturation calculation based on the deep signal was observed
      longitudinally in the patient. With the same technology, arterial input and
      cerebral response functions, generated by iv tracer bolus, were deconvoluted to
      measure mean cerebral transit time. MEASUREMENTS AND MAIN RESULTS: A positive
      linear regression fit between diffuse transmission oximetry and measured blood
      oxygen saturation over the range 23% to 99% (r2 = .98, p less than .001) was
      noted. CONCLUSIONS: The approach used overcomes previously identified
      difficulties with cerebral oximetry, and demonstrates excellent in vitro
      correlation. The technique can be performed clinically without difficulty. A
      simultaneous measure of mean cortical transit time is possible.

PMID- 1986895
TI  - Single versus double indicator dilution measurements of extravascular lung water.
AB  - OBJECTIVE: To compare a simplified method of measuring extravascular lung water
      (EVLW) using only a single indicator (EVLW-SI) with the standard double indicator
      dilution technique (EVLW-DI). DESIGN: Direct comparison of EVLW-SI with EVLW-DI
      in 18 critically ill patients. SETTING: A general medical ICU in a university
      affiliated hospital. PATIENTS: Nine men and nine women, ages 19 to 80 yr. Six
      patients were in shock (four from septic shock), and 11 were in respiratory
      failure. INTERVENTIONS: EVLW-DI and cardiac output were measured in triplicate
      during injection of cold indocyanine green dye. Cardiac output was calculated
      both from pulmonary artery (COpa) and femoral artery (COfem-di) thermal dilution
      signals. EVLW-SI and COfem-si were also measured during three additional
      injections of cold saline using only thermal signals from the pulmonary and
      femoral arteries. Order of measurements was random. EVLW-SI was measured in ten
      patients while blood was withdrawn through the femoral catheter and in ten
      patients without blood drawn through the femoral catheter. MEASUREMENTS AND MAIN
      RESULTS: A total of 84 comparisons were made. Although the overall correlations
      were good (r2 = .86), EVLW-SI systematically overestimated EVLW-DI (p less than
      .05). This difference was greater when EVLW-SI was measured without blood
      withdrawal through the femoral catheter. In this subgroup, mean values for EVLW
      by the two methods were within 20% of one another in only two of ten patients, in
      contrast to the results in six of eight patients in which blood was withdrawn
      through the catheter. COfem-si and COfem-di also overestimated COpa. CONCLUSIONS:
      Theoretically, neither injection of green dye nor blood withdrawal should be
      necessary during measurements of EVLW-SI, making it a simpler technique for
      bedside use than EVLW-DI. However, significant discrepancies exist between the
      two techniques. Some of this difference is apparently due to technical factors
      related to catheter design. In any case, we cannot recommend use of the single
      indicator dilution technique at present to estimate EVLW.

PMID- 1986897
TI  - Influence of infusion pumps on the pharmacologic response to nitroprusside.
AB  - OBJECTIVE: To compare the relationship between variability in nitroprusside
      delivery from five infusion pumps and the resulting variability in mean arterial
      pressure (MAP). DESIGN: Randomized, crossover study design. SETTING: A pediatric
      ICU in a university hospital. PATIENTS: Informed parental consent was obtained
      for six patients who were hemodynamically stable and receiving a continuous
      nitroprusside infusion for a clinical application. Subjects ranged in age from 11
      months to 9 yr. INTERVENTIONS: All of the subjects were administered
      nitroprusside using selected infusion pumps, which included Abbott (Micro),
      3M/AVI (210), IMED (965), IVAC (565), and Kendall McGaw (MicroRate). MEASUREMENTS
      AND MAIN RESULTS: After an initial equilibration interval for each device, MAP
      was measured and recorded at 10-sec intervals for greater than or equal to 90-min
      intervals using a computerized data collection technique. Variation in
      nitroprusside administration (flow continuity) for each infusion pump was
      determined in vitro using a computerized gravimetric technique. Variation in both
      MAP and flow continuity was mathematically expressed as the coefficient of
      variance (CV) of the measured values for each of the respective infusion pumps.
      For the Abbott, IMED, 3M/AVI, IVAC, and Kendall McGaw, infusion pumps, mean +/-
      SD continuity CV values were 85 +/- 31%, 39 +/- 26%, 19 +/- 8%, 17 +/- 3%, and 12
      +/- 3%, respectively, and MAP CV values were 18 +/- 21%, 15 +/- 11%, 8 +/- 2%,
      and 16 +/- 10%, respectively. CONCLUSIONS: An apparent direct relationship
      between MAP variability and flow continuity was observed. We speculate that
      variation in effect of potent short-acting drugs may, in part, be due to infusion
      pump operation.

PMID- 1986898
TI  - Registration, licensing, and certification: understanding the value of each.

PMID- 1986899
TI  - CDEs in 1990: a report of years 3 and 4 (1988 and 1989) of the certification
      process.

PMID- 1986900
TI  - Weight loss from inappropriate insulin manipulation: an eating disorder variant
      in an adolescent with insulin-dependent diabetes mellitus.
AB  - This is the first in a series of papers being sponsored by the Psychosocial
      Committee of AADE that will highlight psychosocial issues encountered in the
      treatment of diabetes. The present case describes the assessment, diagnosis, and
      treatment of a young woman with IDDM who inappropriately manipulated her insulin
      to lose weight. The discussion focuses on the role of the diabetes treatment team
      in the early detection and prevention of maladaptive weight-loss behaviors. This
      is achieved through routine assessment, diabetes-specific dietary counseling, and
      the education of young patients and their parents on the serious health and
      financial consequences of inappropriate insulin a adjustment.

PMID- 1986901
TI  - Diabetes care in schools: benefits and pitfalls of Public Law 94-142.
AB  - The implementation of the Education for All Handicapped Children Act of 1975 (Pub
      L No. 94-142) has brought significant changes in educational services for health
      impaired children. Health-related services are one of many important services
      available to children under Pub L No. 94-142. For some children with IDDM,
      specific diabetes-related care is essential for continued progress in school.
      However, barriers exist that impede access to related health support services,
      including lack of agreement about the applicability for Pub L No. 94-142 to
      children with IDDM, lack of consensus as to who should provide services, and
      concern about liability of school personnel. This paper describes those barriers
      and suggests approaches to overcome them. One such approach is an Indiana State
      legislative amendment that provides schools with immunity from civil liability
      for diabetes-related care.

PMID- 1986902
TI  - Empowerment: an idea whose time has come in diabetes education.
AB  - We have learned much in the past 10 years about how to help patients to acquire
      diabetes-related knowledge and skills and how to use strategies to help patients
      change behaviors. However, the application of knowledge and techniques should be
      guided by a relevant, coherent, educational philosophy. Empowerment offers a
      practical conceptual framework for diabetes patient education. Empowering
      patients provides them with the knowledge, skills, and responsibility to effect
      change and has the potential to promote overall health and maximize the use of
      available resources. It is an idea whose time has come for diabetes education.

PMID- 1986903
TI  - Diabetes care organization, process, and patient outcomes: effects of a diabetes
      control program.
AB  - Effects of a diabetes control program were evaluated in 17 primary health centers
      after 18 months' participation (17 nonparticipating centers served as controls).
      Studied were the effects of the program on the organization of diabetes care, on
      the process of care in terms of services delivered to patients, and on the
      outcomes of care as measured by improved self-care, dietary knowledge, and HbA1c
      values. While findings showed that patients from the intervention centers
      received a higher quality of service and monitored their blood glucose levels
      more often than did patients from the control centers, they did not demonstrate
      significantly better metabolic control. The reasons for this, and ways to improve
      the program are discussed.

PMID- 1986905
TI  - Smoking, cessation, and the diabetes health care team.
AB  - Cigarette smoking is a major risk factor in diabetes and contributes to the
      development of microvascular and macrovascular complications. Despite this,
      approximately one third of patients with diabetes smoke. Nicotine is physically
      and psychologically addictive, with multiple factors contributing to the
      initiation and continuation of the habit. Cessation is a process in which the
      smoker progresses through several stages of change, including precontemplation,
      contemplation, action, maintenance, and relapse. Knowledge of this process is
      needed for the diabetes health care team to effectively individualize smoking
      prevention and cessation strategies. This stepped care approach includes
      preventive, behavioral, and pharmacologic strategies as a component of routine
      diabetes education.

PMID- 1986904
TI  - Impact of a camp experience on choice of coping strategies by adolescents with
      insulin-dependent diabetes mellitus.
AB  - Summer camps for children with IDDM have allowed educators to expand diabetes
      curricula and test novel approaches to education. Yet few evaluations have been
      published assessing the effectiveness of these types of educational
      interventions. The present study was designed as a formative assessment to
      provide preliminary evaluation of the impact of a life skills curriculum designed
      to increase awareness of different techniques that may be useful in managing
      stress. Life skills curricula are included each year as part of the teen session
      at the Texas Lions Camp for Children with Diabetes. Following the intervention,
      campers reported an intent to use more problem-focused and fewer detachment
      strategies to deal with a personally identified stressor. Limitations of the
      current pilot study are used to illustrate problems inherent in evaluation of
      camp programs.

PMID- 1986906
TI  - Certification for diabetes educator: preparation course.

PMID- 1986907
TI  - [The immunopathology of atopic dermatitis].

PMID- 1986908
TI  - [Friedrich Wegener].

PMID- 1986909
TI  - [The drug-induced lysis of gallstones].

PMID- 1986910
TI  - [Blood group determination and blood transfusion].

PMID- 1986911
TI  - [Intravascular sonography of the coronary vessels following percutaneous
      transluminal angioplasty].
AB  - Intravascular ultrasound imaging was performed in 15 patients (three women and 12
      men; mean age 55 [48-70] years) after percutaneous balloon angioplasty of the
      right coronary artery (7 patients), the anterior interventricular branch (6) or
      the circumflex branch of the left coronary artery (2). The catheter, external
      diameter 4.8 F, was advanced over a 0.014--in coronary wire to the area of the
      previously balloon-dilated stenosis. Vessel diameter measured by ultrasound
      correlated closely with that by angiography (r = 0.93; P less than 0.001).
      Ultrasound imaging distinguished between concentric and eccentric intimal
      thickening and made it possible to assess the consistency and degree of
      calcification of the wall changes. The success of angioplasty was evaluated in 10
      patients. In eight, local dissection was revealed, but only three of them had
      been diagnosed angiographically. In one patient a vessel spasm was recorded
      during ultrasound imaging; it regressed after the intracoronary injection of 0.2
      mg nitroglycerin. There were no other complications. The method made it possible
      to assess in vivo the extent and consistency of atherosclerotic plaques, and it
      adds to the angiographic monitoring of treatment results and of complications
      after angioplasty.

PMID- 1986912
TI  - [An association of arterial occlusive disease with cyclosporine therapy after
      kidney transplantation].
AB  - Renal transplantation followed by immunosuppression with cyclosporine (whole
      blood levels 200-300 micrograms/l) and methylprednisolone (4 mg daily) was
      performed in a 54-year-old man with chronic glomerulonephritis. Three years later
      rapidly progressive arterial obstructive disease (peripheral type) developed.
      Parenteral treatment with prostaglandins, calcium antagonists and nitrates, as
      well as a lumbar sympathectomy, was unsuccessful so that, in rapid succession,
      several amputations on upper and lower limbs became necessary. The disease
      progression was arrested only when azathioprine replaced cyclosporine. Raynaud's
      phenomenon, present at the time, also disappeared and analgesics were no longer
      required. Histological examination revealed severe Monckeberg arteriosclerosis
      and thromboembolic occlusion of the affected vessels. The cyclosporine treatment,
      especially the hypercoagulability induced by it, and the Monckeberg
      arteriosclerosis were thought to be significant factors in the pathogenesis of
      the rapidly progressive arterial disease. It is concluded that, in the presence
      of progressive arterial obstructive disease occurring under cyclosporine
      treatment, the replacement by other immunosuppressive agents should be
      considered.

PMID- 1986913
TI  - Mediation of the stress-induced prolactin release by hypothalamic histaminergic
      neurons and the possible involvement of vasopressin in this response.
AB  - We investigated the role of histamine (HA) in the neuroendocrine regulation of
      PRL secretion in conscious male rats. Blood samples were obtained by decapitation
      of the animals at 0 min. Intracerebroventricular infusion of HA (34-540 nmol at 
      15 min) stimulated PRL secretion dose dependently with an ED50 of approximately
      135 nmol. Inhibition of neuronal HA synthesis by the specific histidine
      decarboxylase-inhibitor (S)alpha-fluoro-methylhistidine (alpha FMH; 100 mumol/kg
      ip at -6 h or 400 mumol/kg ip at -20 h and -6 h) caused a 50% reduction (P less
      than 0.01) in the PRL response to 5 min of restraint stress. Inhibition of
      neuronal HA metabolism by the specific histamine-methyltransferase-inhibitor SKF
      91488 (400 and 800 nmol icv at -20 min) augmented the restraint stress-induced
      PRL release 26% and 37%, respectively (P less than 0.05). The two enzyme
      inhibitors had no or only modest effect on the basal PRL secretion. Pretreatment
      with a specific antiserum (0.5 ml) to arginine vasopressin (AVP) or an AVP
      antagonist (25 nmol) administered iv at -20 min inhibited the PRL response to HA
      (270 nmol icv) 80% and 45%, respectively (P less than 0.01) and inhibited the PRL
      response to restraint stress 70% (P less than 0.01). In contrast, pretreatment
      with a specific oxytocin (OT) antagonist (50 nmol) had no effect on the HA- or
      stress-induced PRL release. The AVP antiserum showed less than 0.0003% cross
      reactivity with OT, and radiolabeled OT did not bind to serial dilutions of
      plasma from rats treated with the AVP antiserum. The AVP antiserum or the AVP
      antagonist almost prevented the PRL release induced by iv infusion of 800 pmol
      AVP or a posterior pituitary extract. Infusion of AVP (24-800 pmol iv at -15 min)
      stimulated PRL secretion dose dependently. However, the dose of AVP (800 pmol)
      required to induce an increase in plasma PRL similar to that obtained by HA
      stimulation, led to a rise in plasma AVP which was approximately 1000-fold higher
      than that induced by HA, which increased plasma AVP 2-fold. Restraint stress had
      no effect on the plasma AVP level. We conclude that neuronal HA participates in
      the mediation of the PRL response to stress and that the stress- and HA-induced
      release of PRL may involve AVP, whereas an involvement of OT seems
      unlikely.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1986914
TI  - Preferential increase in pituitary prolactin versus vasoactive intestinal peptide
      as a function of estradiol benzoate dose in the ovariectomized rat.
AB  - Vasoactive intestinal peptide (VIP) is synthesized in various tissues, including
      the anterior pituitary gland, where it may stimulate the release of PRL. Because
      estrogen plays a central role in the regulation of PRL, it becomes important to
      determine the effects of this steroid on both pituitary VIP and PRL. To study
      this, pituitary VIP and PRL and plasma PRL were assayed in ovariectomized rats
      after treatment with estradiol benzoate (EB; 0.007, 0.07, 0.7, 7 or 70
      microgram/rat). Pituitary and plasma TSH were also determined as well as VIP
      content in the medial basal hypothalamus, suprachiasmatic region, cerebral
      cortex, and jejunum. Oil-treated rats served as controls. Injection of 0.7 or 7
      microgram EB resulted in a significant increase in pituitary PRL without changing
      plasma PRL levels or pituitary VIP content compared to values in the control
      group. Only treatment with 70 microgram EB produced a significant increase in
      both pituitary VIP and PRL as well as in plasma PRL compared to control values.
      EB treatment at any of the doses used had no significant effect on pituitary and
      plasma TSH or VIP content in any of the other tissues examined. These data show
      that pituitary PRL and VIP are differentially regulated in response to estrogen.
      The increases in pituitary VIP and basal plasma PRL after treatment with the
      highest dose of EB suggest that pituitary VIP may be involved in the development
      of estrogen-induced hyperprolactinemia. These data also show that the regulations
      of pituitary VIP and TSH are independent of each other in the estrogen-treated
      rat.

PMID- 1986915
TI  - The effect of surgical stress on the in vitro metabolism of thyroxine by rat
      liver, kidney, and brain.
AB  - In man, acute stress, like extensive surgery, leads to a rapid and prolonged
      decrease in serum T3 concentrations. The present study was carried out to
      investigate the mechanisms that underly the abrupt decrease in T3-neogenesis that
      occurs in response to acute surgical stress. Male Sprague-Dawley rats, surgically
      thyroidectomized, and treated with 1.2 micrograms T4/100 g BW/day, underwent wide
      vertical and horizontal incisions extending into the abdominal cavity while
      receiving light ether anesthesia. Different dietary manipulations were performed
      to investigate the superimposed influence of reduced carbohydrate and caloric
      intake on T3-neogenesis. The metabolism of 125I T4 labeled in its outer
      (phenolic) ring was investigated in liver, kidney, and brain homogenates of
      animals killed 48 h after surgery. In liver, values for the proportion of T4
      degraded and the percent generation of T3 and iodide were unaffected by
      laparotomy. The percent T3 generation in experiments with 25 nM T4 concentration
      was 3.7 +/- 1.24% (mean +/- SD) in fed control animals given free access to 5%
      glucose, 3.4 +/- 0.67% in unoperated controls given a restricted amount of chow
      and 5% glucose, and 3.8 +/- 0.67% in operated animals given free access to chow
      and 5% glucose. As expected, T3 neogenesis in livers from unoperated animals was
      significantly reduced in rats fasted for 48 h and this reduction was similar in
      laparotomized rats fasted for 48 h after surgery. As in the liver, no effect of
      laparotomy on T4 metabolism in kidney and brain homogenates was observed.
      Finally, serum total T4 and T3 concentrations were not affected by surgery. It is
      concluded that acute surgical stress in thyroidectomized T4 replaced rats does
      not influence T4 metabolism in liver, kidney, and brain homogenates or affect the
      serum T4 and T3 concentrations. Since thyroid secretion of T4 (and T3) was
      eliminated and careful attention was paid to caloric intake in this rat model,
      previously reported abnormalities in serum thyroid hormone concentrations and T3
      neogenesis in various states of nonthyroidal illness in man and rat, including
      surgery, are probably contributed to by thyroid secretion of T4 (and T3) and
      caloric deprivation, especially carbohydrate.

PMID- 1986916
TI  - Variable prevalence of lymphocytic thyroiditis among diabetes-prone sublines of
      BB/W or rats.
AB  - The BB/Wor rat develops spontaneous autoimmune insulin-dependent diabetes
      mellitus (DM) and lymphocytic thyroiditis (LT). Six different inbred sublines of
      this rat model have been selected for studying the pathogenesis of DM and,
      thereby, the prevalence of DM has been carefully monitored and found to be
      relatively constant. In contrast, we have observed a striking difference in the
      prevalence and intensity of LT in these six sublines, varying from 100% in NB
      subline rats to 4.9% in BE subline rats at 105-110 days of age. Excess iodide
      administration frequently increases the prevalence of LT but did not do so in the
      two sublines (BB and BE) with the lowest frequency of spontaneous LT. In view of
      this variable prevalence of LT in the different BB/Wor sublines, it is imperative
      that investigators studying the pathogenesis and modulation of LT in this rat
      model select those sublines which express a desired frequency of spontaneous LT.

PMID- 1986918
TI  - Role of endogenous angiotensin II in the control of vasopressin secretion during
      hypovolemia and hypotension in conscious rabbits.
AB  - In order to investigate the physiological role of angiotensin II (ANG II) in the
      control of vasopressin (VP) secretion, the VP responses to hypotension induced by
      hemorrhage (20 ml/kg, n = 10) or nitroprusside infusion (1-10 micrograms/kg.min,
      n = 9) were studied with or without blockade of ANG II formation by the
      converting enzyme inhibitor captopril in conscious rabbits. Administration of
      captopril (5 mg/kg, iv) caused a small decrease in mean arterial pressure but did
      not enhance the hypotensive response to subsequent hemorrhage or nitroprusside
      infusion. The renin response to both stimuli was enhanced by captopril, whereas
      the increase in plasma ANG II concentration was attenuated. Plasma VP (PAVP)
      concentration increased during hemorrhage (2.0 +/- 0.2-113.6 +/- 47.7 pg/ml, P
      less than 0.01) and nitroprusside infusion (2.1 +/- 0.3-5.1 +/- 1.0 pg/ml, P less
      than 0.01). Captopril did not change basal plasma PAVP, nor did it attenuate the
      VP responses to hemorrhage or nitroprusside. Indeed, captopril tended to enhance
      the VP responses to hemorrhage (2.3 +/- 0.3-147.1 +/- 65.9 pg/ml) and
      nitroprusside infusion (1.9 +/- 0.2-15.4 +/- 6.0 pg/ml). The relationship between
      log PAVP and mean arterial pressure during hemorrhage and nitroprusside infusion
      in the presence of captopril was not different than in the absence of captopril.
      These results indicate that in conscious rabbits, the renin-angiotensin system
      does not contribute to the increase in VP secretion during hypotension induced by
      hemorrhage or nitroprusside infusion.

PMID- 1986917
TI  - Chromogranin A: posttranslational modifications in secretory granules.
AB  - The primary structure of chromogranin A indicates multiple domains which might be
      subject to posttranslational modification. We explored chromogranin A's
      proteolytic cleavage, glycosylation, and possible intermolecular disulfide links,
      using biochemical and cell biological approaches. Anti-chromogranin A region
      specific immunoblots on chromaffin granules suggested bidirectional
      endoproteolytic cleavage of chromogranin A; control experiments ruled out
      artifactual cleavage during granule isolation or lysis. Isolation of chromogranin
      A-derived peptides by gel filtration chromatography or sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE), followed by N-terminal amino acid
      sequencing, established several cleavage sites, including at least two at dibasic
      sites. Secretion of chromogranin A from bovine chromaffin cells did not initiate
      further cleavage, nor did prolonged exposure of secreted chromogranins to the
      secretory cells. The chromogranin A cleavage pattern was qualitatively similar in
      other neuroendocrine tissues, though cleavage was more complete in adrenal
      medullary than in anterior pituitary hormone storage vesicles, and N-terminal
      fragments of 45 and 55 kilodaltons were more prominent in the hypothalamus. A
      similar cleavage pattern was seen in human pheochromocytoma granules, as judged
      by chromogranin A region-specific immunoblots, fragment isolation by SDS-PAGE,
      and microsequencing. The presence of full-length chromogranin A as the core
      protein of a chromaffin granule soluble proteoglycan was suggested in bovine (but
      not human) chromaffin granules by glycoprotein staining, chondroitinase ABC
      digestion, chemical deglycosylation, and region-specific immunoblotting. Human
      (but not bovine) chromogranin A displayed intermolecular disulfide crosslinks on
      SDS-PAGE gels and immunoblotting. These results document diverse structural paths
      that the chromogranin A molecule may take in endocrine secretory cells after its
      translation.

PMID- 1986919
TI  - Immunoreactive methionine-enkephalin secretion by porcine uterus.
AB  - The current study examined the presence of immunoreactive methionine-enkephalin
      (ir-MENK) in porcine uterine fluid and endometrial extracts, characterized ir
      MENK biochemically, and investigated the effect of ovarian steroids on uterine
      secretion of ir-MENK. Porcine uterine fluid was collected by flushing the uterine
      lumen with saline. Endometrial tissues were extracted with acetic acid. Both
      uterine fluid and endometrial extracts exhibited inhibition curves parallel to
      that of authentic MENK in the MENK RIA system. Sephadex G-15 gel filtration
      chromatographic profiles indicated that both concentrated uterine fluid and
      endometrial extracts contained two peaks of ir-MENK, a major peak which coeluted
      with standard MENK, and a minor peak eluting near the void volume (Vo). Reverse
      phase-HPLC chromatographic profiles also demonstrated two peaks of ir-MENK for
      concentrated uterine fluid and endometrial extracts, a major peak which coincided
      with standard MENK, plus a highly hydrophilic peak. The effect of ovarian
      steroids on the uterine secretion of ir-MENK was examined by measuring ir-MENK in
      uterine fluids from cyclic and pregnant gilts as well as ovariectomized, ovarian
      steroid-treated gilts. Day effects (P less than 0.01) were detected for cyclic
      and pregnant gilts, since values for ir-MENK increased between days 8 and 14
      after onset of estrus. In ovariectomized gilts, treatment with progesterone (P4)
      increased the uterine secretion of ir-MENK (202 +/- 9 vs. 65 +/- 4 pg/ml for
      control, P less than 0.05). The combined treatment of P4 and estradiol did not
      further enhance secretion of ir-MENK, while treatment with estradiol did not
      alter ir-MENK levels relative to values for control gilts. These results indicate
      the presence of ir-MENK in porcine uterine fluid and endometrium, and suggest
      that uterine secretion of ir-MENK is regulated primarily by P4.

PMID- 1986920
TI  - Identification of osteoclast precursors in multilineage hemopoietic colonies.
AB  - The osteoclast is known to be derived from the hemopoietic stem cell, but its
      lineage and the mechanisms by which its differentiation is regulated are largely
      unknown. There is evidence that osteoclastic differentiation is induced through a
      contact-dependent interaction between bone marrow stromal cells and hemopoietic
      precursors. To analyze osteoclastic lineage, colonies were generated in semi
      solid medium from mouse spleen cells in the presence of erythropoietin with
      either Wehi 3B-conditioned medium or interleukin 3 (IL3). After 7 days,
      individual colonies were picked. Half of each colony was phenotyped by the
      morphology of cells in cytospin preparations; the second half of each was
      incubated for 7 days with a bone marrow-derived cell line (ts8) that induces
      osteoclastic differentiation from hemopoietic cells, on bone slices in the
      presence of 1,25-dihydroxyvitamin D3. After incubation, bone resorption was
      assessed by scanning electron microscopy. No resorption was induced in cells
      derived from single-lineage colonies, but resorptive cells differentiated in 17%
      of granulocyte-macrophage (GM) colonies and 38% of multilineage colonies. Since
      only a minority of GM colonies contained osteoclastic precursors, this suggests
      that the GM colonies that contained osteoclasts were not typical GM colonies but
      may have been a form of multilineage colony analagous to other multilineage
      colonies that contain granulocytes, macrophages, and a third cell type. No
      resorptive cells were formed when IL3-derived colonies were incubated on bone
      slices without ts8 cells. The results suggest that osteoclasts are derived from a
      multilineage precursor, upon which IL3 acts to generate cells capable of
      osteoclastic differentiation, which form resorptive cells upon incubation with
      bone marrow stromal cells in the presence of 1,25-dihydroxyvitamin D3.

PMID- 1986921
TI  - Calcium-calmodulin and calcium-phospholipid dependent phosphorylation of
      membranous fraction proteins related to the tropic regulation by estradiol in the
      corpus luteum.
AB  - Estradiol assumes a major role in the regulation of growth, vascularization, and
      progesterone synthesis in the midpregnant rat corpus luteum. To explore whether
      molecular events triggered by estradiol could be mediated, at least in part, by
      protein phosphorylation, we investigated whether estradiol treatment in vivo
      affects endogenous luteal protein phosphorylation systems detectable in vitro.
      Luteal nuclear, mitochondrial, and microsomal fractions were obtained by
      differential centrifugation from rats hypophysectomized and hysterectomized on
      day 12 of pregnancy and treated with or without estradiol for 72 h. Using [gamma
      32P]ATP as phosphate donor, proteins were phosphorylated in the presence or
      absence of either calcium (Ca), Ca plus calmodulin, or Ca plus phospholipid.
      Phosphoproteins were separated by one-dimensional sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and visualized by autoradiography. The
      Coomassie blue stained proteins and phosphoprotein profiles were markedly
      different in the various fractions. Estradiol treatment in vivo caused an
      increase in the basal endogenous phosphorylation of several proteins in vitro. It
      also substantially enhanced the protein kinase C (PKC) and Ca-calmodulin kinase
      dependent phosphorylation of selected proteins in subcellular fractions. The Ca
      calmodulin kinase catalyzed phosphorylation of microsomal 56 and 60 kilodalton
      (kDa) proteins was remarkably increased by estradiol. Proteins (56 and 60 kDa)
      were also phosphorylated when Ca-calmodulin was added to the nuclear fraction,
      however, this phosphorylation did not appear to be affected by estradiol
      treatment. A major PKC substrate in the nuclear fraction was an 80 kDa protein
      whose phosphorylation was increased remarkably by estradiol treatment. In the
      mitochondrial fraction the most striking effect of estradiol was a marked
      increase in PKC-mediated phosphate transfer into a 76 kDa substrate. To determine
      whether estradiol action on protein phosphorylation was related to its tropic
      effect in the corpus luteum, the hormone was administered to day 10
      hypophysectomized and hysterectomized pregnant rats. In this rat model, where
      estradiol has no stimulatory effect on either luteal steroidogenesis or growth,
      neither endogenous nor kinase-mediated phosphorylation was affected by this
      steroid. In summary, the present investigation has revealed that in vivo
      treatment with estradiol affects the PKC and the Ca-calmodulin dependent in vitro
      phosphorylation of selected proteins localized in different subcellular
      compartments and further suggests that phosphorylation systems are potential
      control points for estradiol regulation of rat corpus luteum function.

PMID- 1986922
TI  - Ultrastructural evidence for luteinizing hormone-releasing hormone neuronal
      control of estrogen responsive neurons in the preoptic area.
AB  - Both estrogen receptor (ER) immunoreactive (ir) and LHRH-ir neurons and processes
      are present in the preoptic area of the guinea pig. This experiment was conducted
      to determine if LHRH-ir terminals interact synaptically with ER-ir cells. A light
      microscopic dual chromogen immunocytochemical technique employing
      diaminobenzidine (DAB) and nickel-enhanced DAB for LHRH and ER localization,
      respectively, revealed that many varicose LHRH-ir fibers coursed in close
      proximity to ER-ir cells in the anterior part of the preoptic area at the
      preventricular periventricular nucleus (Pep), suggesting the likelihood of
      synaptic interactions. Ultrastructural analysis was performed using DAB and
      3,3',5,5'-tetramethylbenzidine (TMB) for LHRH and ER localization, respectively.
      DAB labeling in LHRH-ir neurons appeared as a dense flocculent product dispersed
      throughout the cytoplasm. TMB stained ER-ir neurons contained electron dense
      crystalline spicules located predominantly in their nuclei. Numerous TMB labeled
      ER-ir neurons were present in the Pep, and occasionally occurred in clusters,
      closely apposed to one another. Many LHRH-ir terminals made synaptic contact or
      were apposed to unlabeled dendrites, while fewer contacted perikarya. Most
      significantly, ER-ir neurons showing clear evidence of intranuclear TMB crystals
      received synaptic input from LHRH-ir terminals. In addition, LHRH-ir terminals
      lacking synaptic specializations were also in direct apposition to ER-ir
      perikarya. These results provide morphological evidence that LHRH-ir neurons can
      regulate ER-ir neurons in the preoptic area. Since LHRH-ir cells are thought to
      be regulated by estrogen responsive neurons, interaction of LHRH terminals with
      ER-ir cells may represent a regulatory feedback circuit between the two systems.

PMID- 1986923
TI  - Autoradiographic evidence of nuclear binding of spironolactone in rabbit cortical
      collecting tubule.
AB  - Previous biochemical studies indicated that the spirolactone-mineralocorticoid
      receptor complexes are unable to translocate into the nucleus. The present study
      was designed to reinvestigate the intracellular distribution of spirolactone
      binding sites, using autoradiography. For this purpose, rabbit kidney pyramids
      were incubated at 30 C with tritiated SC9420 or aldosterone. Thereafter,
      aldosterone-sensitive cortical collecting tubules were microdissected and
      processed for dry film autoradiography. The concentration was 2 nM for both
      steroids. Non-specific labeling was determined by incubations with tritiated
      steroids plus a 100-fold excess of unlabeled steroids. Results show the presence
      of specific nuclear labeling for both [3H] aldosterone and [3H]SC9420. Specific
      cytoplasmic labeling was very low for both [3H]aldosterone and [3H]SC9420. The
      nuclear labeling by [3H]SC9420 was equally and almost completely displaced by a
      100-fold excess of unlabeled aldosterone or SC9420 (91% and 87%, respectively).
      We conclude that spironolactone-receptor complexes migrate into the nucleus. The
      difference between these results and those of previous studies with biochemical
      techniques, which failed to detect specific nuclear binding of spirolactone, may
      be due to methodological reasons.

PMID- 1986924
TI  - The gonadotropin-releasing hormone associated peptide reduces calcium entry in
      prolactin-secreting cells.
AB  - The precursor molecule to the GnRH contains a peptide named GnRH-associated
      peptide (GAP) with PRL-inhibiting properties. In this work, we have studied the
      electrophysiological properties and responses to GAP of three different types of
      PRL-secreting cells: 1) the rat tumor cell line GH3, 2) normal rat pituitary
      cells in primary culture, and 3) human PRL-secreting adenoma cells. Using
      different but complementary techniques we show that GAP reduces intracellular
      Ca++ levels, [Ca++]i, and inhibits Ca++ transients in these cells. This reduction
      of [Ca++]i results from coordinate actions of GAP on K+ and Ca++ conductances and
      may explain the inhibitory effect of GAP on hormonal secretion by PRL-secreting
      cells.

PMID- 1986925
TI  - Pharmaceutical research is expensive but well worth the cost.

PMID- 1986926
TI  - Localization of progesterone receptors in pre- and postovulatory follicles of the
      domestic hen.
AB  - Progesterone may act locally to modulate follicular maturation and ovulation in
      the domestic hen. The distribution of progesterone receptors (PR) in the pre- and
      postovulatory follicles was determined in hens by immunocytochemistry and Western
      blot analysis. Monoclonal antibodies to chicken PR, PR6, and PR 13, were used. PR
      were localized in nuclei of theca externa fibroblasts and germinal epithelial
      cells in stigma and nonstigma regions of the third largest preovulatory follicle
      (F3). In the largest preovulatory follicle (F1), PR were present in theca externa
      fibroblasts, germinal epithelial cells, and also in granulosa cells and some of
      the theca interna fibroblasts in the stigma and nonstigma region. Twenty-four
      hours after ovulation, PR in the fibroblasts of the theca externa of the
      postovulatory follicle (POF) were remarkably reduced, but the amount of PR in the
      granulosa cells was similar to that observed in the F1. A high density of PR was
      also found in the fibroblasts, arterial wall, and smooth muscle fibers in the
      loose connective tissue of pre- and postovulatory follicles. Western blot
      analysis indicated that PR in the granulosa and theca tissue were identical in
      molecular weight to PR in the shell gland. Western blot analysis also confirmed
      the changes in the amounts of PR in the pre- and postovulatory follicles as
      determined by immunocytochemistry. The relative amounts of PR in the granulosa
      cells as determined by Western blot analysis was F2 less than F1 = POF, and in
      theca tissue was F2 = F1 greater than POF. The presence of PR in specific ovarian
      tissues suggests that these tissues are target tissues for progesterone and that
      progesterone may have a role in regulating follicular maturation and ovulation
      through receptor-mediated pathways.

PMID- 1986927
TI  - Androgen receptor messenger ribonucleic acid (mRNA) in the rat liver: changes in
      mRNA levels during maturation, aging, and calorie restriction.
AB  - By means of RNAase protection assay with an antisense cRNA probe, we have shown
      that the liver of the young adult male rat contains androgen receptor (AR) mRNA
      to a level of 4% compared to the prostate. Steady state levels of AR mRNA in the
      liver show both sex and age specificity. Compared to that of the male, the female
      liver contains a markedly reduced amount of AR mRNA. AR mRNA is almost
      undetectable in livers of prepubertal male (less than 35 days old) and senescent
      male (greater than 750 days old) rats. Both prepubertal and senescent animals are
      relatively insensitive to the androgenic induction of alpha 2u-globulin, a
      hepatic secretory protein. The age-dependent decline in hepatic androgen
      sensitivity and AR mRNA level can be delayed considerably by a 40% reduction in
      the dietary calorie intake. Analysis of poly(A)-containing RNA from two liver
      cell populations, hepatocytes and nonhepatocytes, revealed that only the
      hepatocytes that express alpha 2u-globulin gene contain AR mRNA. From these
      results and our earlier observation of in vitro induction of alpha 2u-globulin in
      isolated rat liver, we conclude 1) that androgen can act directly on hepatocytes
      to promote alpha 2u-globulin synthesis; 2) that changes in the hepatic androgen
      sensitivity during maturation and aging are reflections of the age-dependent
      expression of the receptor gene; and 3) that retardation of the age-dependent
      loss of androgen sensitivity by calorie restriction is due to a concomitant delay
      in the decline of the hepatic AR mRNA level.

PMID- 1986928
TI  - Transforming growth factor beta 1 is a negative regulator of steroid 17 alpha
      hydroxylase expression in bovine adrenocortical cells.
AB  - Transforming growth factor beta 1 (TGF-beta 1) has been shown previously to
      induce striking alterations of bovine adrenocortical cell steroidogenic
      functions. One of the major lesions was characterized as a loss of steroid-17
      alpha-hydroxylase activity, a key step in the biosynthetic pathway leading to
      active corticosteroid hormones. The mechanism of this negative effect of TGF-beta
      1 on adrenocortical differentiated functions was investigated. It was observed
      that: 1) bovine adrenocortical 17 alpha-hydroxylase activity rapidly decreased in
      cells exposed to TGF-beta 1, in a time (10-20 h)-dependent manner; 2)
      immunoblotting of the corresponding cytochrome P-450(17) alpha showed that the
      loss of activity was superimposable to the decrease of the cellular protein
      content; 3) the cell content in 17 alpha-hydroxylase messenger RNA sharply
      dropped under TGF-beta 1 treatment (70-75% loss within 3-4 h) as determined by
      Northern blot analysis; 4) TGF-beta 1 inhibited as well the induction of P
      450(17) alpha normally observed under adrenocorticotropin treatment; and 5) these
      TGF-beta 1 effects were selectively directed toward P-450(17) alpha expression,
      whereas another major steroidogenic cytochrome, i.e. P-450scc, was not affected.
      These observations showed that TGF-beta 1 is a potent negative modulator of 17
      alpha-hydroxylase expression in bovine adrenocortical cells, very possibly at the
      transcriptional level. TGF-beta 1 (whose gene is expressed in these cells) may
      thus be examined as a possible autocrine inhibitory factor implied in the
      regulation of adrenocortical differentiated functions, in balance with ACTH,
      which represents the major positive signal in this system.

PMID- 1986929
TI  - Immunochemical and immunohistochemical evidence of estrogen-mediated
      collagenolysis as a mechanism of cervical dilatation in the guinea pig at
      parturition.
AB  - The mechanism of dilatation of the uterine cervix at birth is poorly understood.
      Several indirect lines of evidence have suggested that cervical ripening is
      accompanied by collagen degradation. In this study, immunochemical methods have
      been developed to identify and analyze type I collage degradation in the cervix
      of the pregnant guinea pig. Using cyanogen bromide-derived peptides of purified
      guinea pig type I collagen as an immunogen, a polyclonal rabbit antiserum was
      prepared that recognizes epitopes on the denatured and degraded alpha 2 chain of
      type I collagen as demonstrated by enzyme-linked immunosorbant assay and
      immunoblotting. This antibody was used to demonstrate degradation of type I
      collagen in the extracellular matrix of the dilated cervix at parturition.
      Moreover, physiological concentrations of 17 beta-estradiol stimulated
      degradation of type I collagen in the nonpregnant cervix in organ culture.
      Collagenase degradation products were detected in the extracellular matrix and in
      the culture media. The effect of 17 beta-estradiol (10(-6) M) was completely
      blocked by progesterone (10(-4) M). These studies suggest that dilatation of the
      guinea pig cervix at parturition may be associated with estrogen-mediated
      degradation of type I collagen.

PMID- 1986930
TI  - Localization of the androgen receptor in the developing rat gubernaculum.
AB  - The distribution of androgen receptor expression within the developing rat
      gubernaculum was examined at different times during fetal and neonatal
      development using polyclonal antibodies directed at the amino-terminus (amino
      acids 1-21) and the carboxy-terminus (amino acids 898-917) of the androgen
      receptor. These studies reveal a high level expression of androgen receptor in
      the undifferentiated cells that comprise the mesenchymal core of the gubernaculum
      in early development. However, during the morphological alterations of the
      gubernaculum into a muscular structure, the level of androgen receptor detected
      in these cells declines, with minimal immunoreactivity present 2 weeks
      postpartum. Whether the loss of staining of the mesenchyme is related to
      decreases in androgen receptor expression, death of the mesenchymal cells, or
      differentiation of these cells into myoblasts remains to be determined.

PMID- 1986931
TI  - Evidence that human chorionic gonadotropin/luteinizing hormone receptor down
      regulation involves decreased levels of receptor messenger ribonucleic acid.
AB  - Injection of pseudopregnant rats with pharmacological doses of hCG leads to a
      characteristic decrease in LH/hCG binding by the isolated luteal cells. The
      steady state levels of LH/hCG receptor mRNA were determined in rat ovaries during
      hCG-induced down-regulation of the receptor. Northern blots were performed using
      a 20-mer probe corresponding to a guanine cytosine-rich carboxyl-terminal
      untranslated region of the LH/hCG receptor cDNA. The hybridization of the probe
      to LH/hCG receptor mRNA was highly specific, since the probe hybridized only to
      rat luteal cell RNA fraction, with no signal detected in nontarget tissues. The
      LH/hCG receptor level was quantitated by [125I]hCG binding to the isolated
      membrane fractions from the corresponding treatment and control groups.
      Examination of mRNA levels of the receptor during hCG-induced down-regulation
      showed a steady decrease from 0-24 h, followed by a gradual increase to control
      levels from 24-72 h corresponding to days 8-9 of pseudopregnancy. The [125I]hCG
      binding activity during down-regulation paralleled the mRNA profile in both the
      experimental and control groups. Examination of the levels of mRNA for alpha
      actin showed no change during this period, suggesting that the loss of LH/hCG
      receptor mRNA at 24 h was not due to a general loss of mRNA in luteal cells.
      These results suggest that hCG-induced down-regulation of the LH/hCG receptor in
      luteal cells involves regulation of the receptors at the message level.

PMID- 1986932
TI  - The rat glucagon gene is regulated by a protein kinase A-dependent pathway in
      pancreatic islet cells.
AB  - A cAMP response element (CRE) has been identified in the proximal 5'-flanking
      region of the rat glucagon gene, and activation of the cAMP-dependent pathway in
      fetal rat intestinal cells leads to an increase in the levels of glucagon mRNA
      transcripts. In contrast, the human glucagon gene does not contain a similar CRE,
      and the results of studies using immortalized rat and hamster islet cell lines
      have suggested that glucagon gene expression may not be regulated by cAMP. To
      reconcile these observations, we have studied the control of glucagon gene
      expression. Incubation of primary rat islet cell cultures with forskolin in the
      presence of low (0.5 g/liter) or high (2.0 g/L) glucose resulted in a 2- to 3
      fold increase in the levels of glucagon mRNA transcripts. Forskolin also
      stimulated the secretion and synthesis of immunoreactive glucagon. The importance
      of the protein kinase-A-dependent pathway in the regulation of glucagon gene
      expression was also examined in hamster islet InR1-G9 cells. Cotransfection of a
      glucagon-chloramphenicol acetyltransferase (CAT) fusion gene containing the
      glucagon CRE and a cDNA encoding the catalytic subunit of protein kinase-A
      resulted in stimulation of glucagon-CAT activity in hamster islet cells.
      Catalytic subunit cotransfection also activated somatostatin-CAT, but no
      activation of RSVCAT was detected. The results of these experiments suggest that
      the rat glucagon gene is regulated by a protein kinase-A-dependent pathway in the
      endocrine pancreas.

PMID- 1986933
TI  - High concentrations of 17 beta-estradiol stimulate trabecular bone formation in
      adult female rats.
AB  - Although the effects of low concentrations of 17 beta-estradiol (E2) on bone
      formation and resorption are well described, little is known of the effects of E2
      on bone at concentrations that circulate during pregnancy. We, therefore,
      investigated the effects of administration of high dose E2 to 3-month-old female
      Wistar rats on biochemical and histomorphometric indices of bone formation and
      resorption. Animals receiving exogenous E2 (4 mg/kg.day for 17 days; n = 9)
      showed a mean serum E2 concentration of 17.5 +/- 2.9 nM, compared with 0.6 +/-
      0.2 nM in those receiving vehicle alone (n = 10). The bone formation rate,
      measured at the proximal tibial metaphysis after the administration of double
      fluorochrome labels, was greatly increased in the E2 group (13.6 +/- 2.0 x 10(-2)
      microns3/microns2.day) compared to controls (3.9 +/- 0.9), as was serum alkaline
      phosphatase (E2, 133.6 +/- 10.1 IU; controls, 87.5 +/- 5.5). This increase in the
      rate of bone formation was associated with a significant increase in trabecular
      bone volume. E2 treatment did not affect urinary hydroxyproline excretion or
      histomorphometric indices of bone resorption. These findings suggest that high
      concentrations of E2 strongly stimulate the formation of trabecular bone. This
      may represent an important mechanism by which calcium stores are accumulated
      during pregnancy in rats, in anticipation of the mineral requirements of
      lactation.

PMID- 1986934
TI  - Thyroid hormones and 5'-deiodinase in the rat fetus late in gestation: effects of
      maternal hypothyroidism.
AB  - Having previously observed that T4 and T3 levels in fetal rat brain and brown
      adipose tissue are clearly higher than expected from their low circulating
      levels, we have now studied thyroid hormone concentrations and 5'-deiodinase
      activities (5'D) in several other rat fetal tissues during the last 6 days of
      gestation (dg), namely 17-22 dg. This period comprises the onset of fetal thyroid
      activity. Total thyroidal T4 and T3 contents increased 100- and 400-fold,
      respectively; T4 concentrations increased 8- to 10-fold in plasma, carcass, lung,
      and liver, and T3 increased 4.5- to 9-fold, except in plasma and liver, where T3
      levels increased less than 2-fold in plasma and 3-fold in liver. During this
      developmental period 5'D activity increased 5- and 10-fold in fetal liver and
      lung, respectively. In fetuses from hypothyroid [thyroidectomized (T)] dams, body
      weight was lower than in fetuses from normal dams. Total thyroidal T4 and T3
      contents were initially the same, but decreased markedly in fetuses from T dams
      by the end of gestation. At the earliest fetal ages studied (17-18 dg) T4 and T3
      concentrations were lower in carcass, liver, lung, and brain, although near term
      there were no consistent differences between the fetal tissues from T and control
      dams, probably because of compensatory stimulation of thyroidal secretion. Liver
      5'D was decreased by 50% throughout gestation, and lung 5'D activities were lower
      by the end of gestation. Thyroid hormones in placentas from T dams were very low,
      but increased by the end of gestation because of the contribution by the fetal
      thyroid. Present results describe the ontogenic profiles for thyroid hormone
      concentrations and 5'D activities during late fetal development; active
      regulatory mechanisms are already present at this age. It has been frequently
      stated that rat fetuses near term are deficient in thyroid hormones, and that
      their thyroid hormone economy is independent of maternal thyroid status, but
      present results show that near term, T4 and T3 concentrations in several tissues
      reach levels that are 50% or more of those described for adult animals, and that
      fetal thyroid function is influenced by maternal hypothyroidism.

PMID- 1986935
TI  - The hypothalamic-pituitary axis of streptozotocin-induced diabetic female rats is
      not normalized by estradiol replacement.
AB  - Studies in diabetic rats have found abnormalities at the hypothalamic, pituitary,
      and/or ovarian level but have not controlled for changes in estrogen levels
      induced by diabetes. The purpose of this investigation was to study the effect of
      diabetes on the hypothalamic-pituitary axis in ovariectomized rats treated with
      estradiol (E2). Ovariectomized 60 day old female rats were assigned to control
      (C, n = 42), diabetic (D, n = 47) or insulin-treated diabetic (DI, n = 16)
      groups. Diabetes was induced with an injection of streptozotocin in the D and DI
      groups. In the C, D, and DI groups, estrogen was replaced by implanting blank, 5
      micrograms or 20 micrograms E2 pellets sc. Pituitary LH responsiveness to GnRH
      was assessed in C and D animals. Anterior hypothalamic and midhypothalamic
      concentrations of proGnRH and GnRH, pituitary LH and FSH and serum levels of LH,
      and E2 were measured by RIA. Anterior hypothalamic proGnRH concentrations were
      decreased in diabetic rats treated with 5 micrograms E2 compared to 5 micrograms
      E2 control animals (P less than 0.05). Midhypothalamic GnRH concentrations were
      also reduced in D vs. C animals despite comparable estrogen therapy (P less than
      0.004). GnRH-stimulated LH levels were greater in E2-treated diabetic females
      than in similarly treated control rats (P less than 0.001). D and DI animals were
      more sensitive than controls to the inhibitory effect of estrogen on basal LH
      levels. Pituitary LH and FSH content was lower in 20 micrograms E2-replaced
      animals but was not influenced by the diabetic state. These data demonstrate a
      diabetes-induced decrease in hypothalamic proGnRH and GnRH concentration which is
      not corrected with E2 replacement. The hyper-responsiveness of the diabetic rat
      pituitary to GnRH also suggests a chronic lack of GnRH stimulation from the
      hypothalamus but a continued ability of the pituitary to respond to GnRH.

PMID- 1986937
TI  - Role of prolactin versus growth hormone on islet B-cell proliferation in vitro:
      implications for pregnancy.
AB  - This study investigated the effects of homologous rat PRL (rPRL) and rat GH (rGH)
      on islet growth as indicated by modifications in insulin secretion, islet cell
      proliferation, and islet volume with neonatal and adult rat islets in vitro. The
      number of proliferating cells was determined by immunocytochemical staining for 5
      bromo-2'-deoxyuridine (BrdU) incorporated into replicating DNA during the final
      24 h of culture. When neonatal rat islets were examined by laser scanning
      confocal microscopy, more than 90% of the BrdU-labeled nuclei were observed in B
      cells with insulin immunoreactivity. In neonatal rat islets, rPRL was much more
      effective than rGH in increasing insulin secretion (3.7-fold vs. 1.4-fold) during
      the 10 days of culture. The number of BrdU-labeled nuclei per islet was increased
      from 2.9 +/- 0.4 (n = 77) in control islets to 47.3 +/- 2.7 (n = 95) with rPRL
      (16.3-fold) and 9.7 +/- 0.8 (n = 84) with rGH (3.3-fold). The effects of rPRL and
      rGH on both insulin secretion and BrdU labeling were approximately additive.
      After 10 days, an increased average islet volume was only observed with rPRL.
      When followed for 36 days, the total amount of islet tissue was unchanged for
      control islets (1.1-fold), more than doubled with rPRL (2.5-fold), and only
      slightly increased with rGH (1.4-fold). From the observed rates of islet cell
      proliferation and increases in islet volumes, doubling times of 23-24 days for
      rPRL and 89-91 days for rGH can be estimated. Of other proposed islet growth
      factors, cholecystokinin, epidermal growth factor, platelet-derived growth
      factor, and 2-aminoisobutyric acid, an increase in insulin secretion and islet
      cell proliferation was only observed with cholecystokinin in neonatal rat islets.
      However, both effects were less than 20% of those observed with rPRL. In adult
      rat islets, rPRL was also more effective than rGH in increasing insulin secretion
      (1.6-fold vs. 1.2-fold) during the 9 days of culture. The number of BrdU-labeled
      nuclei per islet was increased from 2.7 +/- 0.5 (n = 96) in control islets to 9.5
      +/- 0.6 (n = 175) with rPRL (3.5-fold). In contrast to the neonatal islets, rGH
      had no effect on the number of BrdU-labeled nuclei per islet in adult rat islets
      (2.4 +/- 0.3, n = 194).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1986936
TI  - Regulation of synthesis and secretion of chromogranin-A by calcium and 1,25
      dihydroxycholecalciferol in cultured bovine parathyroid cells.
AB  - A RIA for bovine parathyroid chromogranin-A (CgA) was developed and used to study
      the regulation of CgA synthesis and release in cultured bovine parathyroid cells.
      As previously demonstrated, an elevated medium calcium concentration (2.5 mM) led
      to a reduced release of CgA into the medium. In contrast, the intracellular
      concentration of CgA was not changed by alterations in the medium calcium
      concentration. 1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3] stimulated a dose
      dependent increase in the release of CgA, whereas intracellular CgA levels were
      not markedly altered. Alterations in medium calcium concentration did not affect
      CgA mRNA levels, whereas 1,25-(OH)2D3 caused a time- and dose-dependent increase
      in CgA mRNA levels. Therefore, changes in CgA release occurred in response to
      calcium and 1,25-(OH)2D3, with little change in the intracellular CgA
      concentration. This could arise by a change in the synthetic rate to match the
      alteration in the secretion rate and/or a change in the degradation rate. Calcium
      does not appear to affect CgA synthesis at a pretranslational level, whereas 1,25
      (OH)2D3 stimulated a marked increase in CgA mRNA levels via an effect on CgA gene
      transcription. Furthermore, 1,25-(OH)2D3 had no effect on CgA mRNA stability. The
      relationship between steady state levels of CgA mRNA and total CgA levels
      (intracellular and extracellular) is not simple and possibly indicates that an
      important regulatory step for CgA synthesis occurs at the level of mRNA
      translation. The effect of 1,25-(OH)2D3 on CgA mRNA levels was not modulated by
      medium calcium concentrations. In addition, the effect of 1,25-(OH)2D3 in
      reducing PTH mRNA levels was not affected by medium calcium concentrations, with
      1,25-(OH)2D3 and calcium acting independently to reduce PTH mRNA levels.

PMID- 1986938
TI  - Regulation of placental low density lipoprotein uptake in baboons by estrogen.
AB  - We have previously shown that placental low density lipoprotein (LDL) uptake is
      decreased in baboons treated with antiestrogen and we have proposed, therefore,
      that estrogen regulates placental LDL uptake and use during primate pregnancy. In
      the present study, an alternate in vivo approach was employed to determine
      whether restoration of estrogen in animals in which the formation of estrogen was
      decreased would reverse the decline in LDL uptake. Placental estrogen was
      suppressed by removing the fetus (fetectomy) and thus adrenal androgens on day
      100 of baboon gestation (term is 184 days). Placental LDL uptake was determined
      on day 160 after fetectomy alone, and after fetectomy and sc administration of
      the estrogen precursor androstenedione (50 to 150 mg every 10 days). Placental
      cells (10(6] were dispersed with 0.1% collagenase, isolated via 50% Percoll
      gradient centrifugation, then incubated at 37 C for 12 h in medium 199 with 10
      100 micrograms [125I]LDL and LDL uptake (i.e. binding and internalization)
      determined by Scatchard analysis. In intact baboons and animals that had
      undergone fetectomy, syncytiotrophoblasts predominated and formed a continuous
      surface covering of the placental villi. Moreover, placental cells of intact and
      fetectomized baboons isolated on 50% Percoll consisted primarily of
      syncytiotrophoblasts, as evidenced by their immunohistochemical reaction with
      antisera against placental lactogen and pregnancy-specific-beta 1-glycoprotein.
      Serum estradiol in untreated baboons increased with advancing gestation and mean
      (+/- SE) concentrations were 1.29 +/- 0.04 ng/ml on days 101-160 of gestation.
      Placentas remained in situ and viable after fetectomy, but serum estradiol
      decreased to 0.24 +/- 0.02 ng/ml, or 19% of normal (P less than 0.01).
      Androstenedione restored serum estradiol after fetectomy to a mean of 0.69 +/-
      0.03 ng/ml on days 101-160, or 53% of normal. Specific LDL uptake (nanograms per
      microgram protein) by placental cells after fetectomy alone (3.2 +/- 0.4) was 22%
      (P less than 0.001) of controls (14.4 +/- 1.2). Androstenedione increased (P less
      than 0.005) LDL uptake after fetectomy to a value (8.8 +/- 1.2) that was 61% of
      normal. LDL degradation, which depends on uptake, was 59 +/- 1% of normal after
      fetectomy and restored with androstenedione treatment to 94 +/- 2% of normal.
      Apparent dissociation constants (microgram/ml) for LDL uptake were similar after
      fetectomy (0.38), and fetectomy and androstenedione treatment (0.41), but lower
      (P less than 0.01) than in intact animals (0.80).(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 1986939
TI  - Single cell levels of hypothalamic messenger ribonucleic acid encoding
      luteinizing hormone-releasing hormone in intact, castrated, and
      hyperprolactinemic male rats.
AB  - We have examined the changes that occur in neuronal expression of LHRH mRNA in
      response to castration and hyperprolactinemia in male rats. Single cell levels of
      LHRH mRNA were determined by quantitative in situ hybridization histochemistry
      using an 35S-labeled synthetic 48-base oligodeoxynucleotide probe and
      quantitative autoradiography. Nine days postcastration, a 10.4-fold increase in
      mean plasma LH titers was observed which was associated with significantly
      increased LHRH mRNA in rostral hypothalamic neuronal cell bodies. Both increases
      were blocked in rats rendered hyperprolactinemic by the presence of the 7315a PRL
      secreting pituitary tumor. The location and number of neurons expressing LHRH
      mRNA were unchanged, indicating that these differences were attributable to
      amounts of mRNA expressed per neuron. Experimental differences occurred in LHRH
      perikarya situated throughout the rostral hypothalamus from the organum
      vasculosum of the lamina terminalis to the caudal extent of the medial preoptic
      nucleus. These results suggest that gonadal steroids and PRL are involved, either
      directly or indirectly, in regulating the biosynthesis of LHRH in the rostral
      hypothalamus.

PMID- 1986941
TI  - Antibodies in passive immunization studies: characteristics and consequences.
AB  - Antibodies to neuropeptides or hormones are frequently used in passive
      immunization studies to unravel their physiological role in signal transfer. In
      such in vivo experiments antibodies are considered to bind and thereby to
      biologically inactivate the endogenous substance during its journey from its site
      of secretion to its site of action (signalling time). However, little is known
      about the mechanism of action and characteristics of antibodies that determine
      such biological activity. Since the signalling time in neuronal and hormonal
      communication is short, the kinetics of antibody binding is an important feature.
      Here, we present a theoretical framework to describe antibody binding kinetics
      which can contribute to the design of passive immunization protocols. The
      specific effects of variation in antibody concentration, dissociation constant,
      and on-rate constant on these binding kinetics are demonstrated. Simple methods
      are described to determine these parameters, which may guide the selection of
      antibodies for passive immunization studies. When time is limited, the on-rate
      constant and the local antibody concentration are the most important
      determinants. Several points are illustrated for CRF signal transfer in the rat.
      CRF signalling time in the hypothalamo-pituitary complex, as established from dye
      transport experiments, was 3-7 sec. Based on parameters measured for a rat
      monoclonal antibody to CRF (PFU 83), we computed that half-maximal and full
      blockades of ether-induced ACTH secretion were associated with approximately 85%
      and more than 99% binding of CRF, respectively. From the theoretical framework
      presented in this study we conclude that, in general, the kinetics of antigen
      binding are sufficiently fast for antibodies to interfere with hormonal and
      probably nonsynaptic neuronal signal transfer. However, interference with fast
      signalling processes (less than 10 msec), which may occur in the brain, is
      unlikely.

PMID- 1986940
TI  - Effects of insulin on the synthesis, intracellular degradation, and secretion of
      parathormone.
AB  - Bovine parathyroid organoids were maintained for up to 12 days of culture in the
      presence or absence of insulin. Insulin-treated organoids secreted more PTH and
      secretory protein-I (SP-I) than did untreated organoids at both 1.4 and 1.8 mM
      Ca, concentrations chosen to promote partially elevated and suppressed secretion
      rates, respectively. The insulin effect was dose dependent and reversible. To
      determine whether insulin might increase secretion by reducing degradation of
      cellular PTH, its effects on several parameters related to degradative processes
      were examined. Compared to control cultures maintained at either 1.4 or 1.8 mM
      Ca, insulin did not induce changes in the relative levels of intact hormone and
      COOH-terminal peptide fragments secreted into culture medium, nor did it decrease
      the total cellular levels of three lysosomal enzymes or mute the effects of 3
      methyladenine (an agent that decreases formation of autophagosomes) to increase
      PTH secretion. Thus, insulin did not appear to increase PTH secretion by reducing
      the latter's cellular degradation. Synthesis of total proteins and of the
      secreted proteins SP-I and PTH was examined using short incubations of control
      and insulin-treated organoids with [3H] leucine. Incorporation of 3H into total
      acid-precipitable proteins was not elevated in insulin-treated organoids; that
      into PTH/pro-PTH and SP-I, however, was significantly greater in insulin-treated
      than in control organoids. The results suggested that the insulin-mediated
      increase in PTH and SP-I secretion is largely due to its regulation of PTH and SP
      I biosynthesis.

PMID- 1986943
TI  - Precocious mammary gland development and milk protein synthesis in transgenic
      mice ubiquitously expressing human growth hormone.
AB  - A chimeric gene comprising the hydroxymethylglutaryl coenzyme-A reductase
      promoter and the human GH (hGH) genomic sequences was used to create transgenic
      mice expressing hGH in all tissues. In transgenic females, morphological
      development of the mammary gland and milk protein (WAP) expression commences at 3
      weeks of age. At 8 weeks of age the mammary gland is morphologically and
      functionally comparable to that normally reached after 14-15 days of gestation.
      Precocious development correlated with local expression of hGH in mammary gland.
      Organ culture in the presence of different lactogenic hormones revealed that
      insulin and hydrocortisone are sufficient to maintain transcription of the WAP
      gene in transgenic mammary gland. In contrast, WAP transcription in normal gland
      required either hGH or PRL in addition to insulin and hydrocortisone. However,
      the effect of hGH on mammary differentiation does not appear to be solely
      mediated through an interaction with PRL receptors, since PRL, when added to
      cultured mammary tissues, did not elicit an equivalent response.

PMID- 1986942
TI  - Neuroendocrine regulation of adrenal 5'-monodeiodination during acute cold
      exposure in the rat. I. Effects of hypophysectomy.
AB  - Circulating levels of T4, T3, corticosterone, noradrenaline, and adrenaline, as
      well as 5'-monodeiodinase activity (5'-MA) were measured in control and
      hypophysectomized rats acutely exposed to cold environment (15-120 min, 4 C). In
      addition to the well known activation of the sympathoadrenomedullary system and
      the hypothalamic-pituitary-adrenal and-thyroid axes, cold exposure was followed
      by a rapid and sustained increase of 5'-MA in the hypothalamus, and a byphasic
      course of activation in the adrenal gland in control rats. The adrenal rapid
      activation (30 min) corresponded to the medulla and the slower activation (120
      min) to the cortex. Both, the basal adrenal 5'-MA and the response to cold in
      adrenal and hypothalamus were 2-fold higher in hypophysectomized rats compared to
      control. The time course of enzyme activation in these structures suggests that:
      1) organ-specific increases in 5'-MA may be associated to a simultaneous rise in
      their metabolic and/or functional activity, 2) the triggering mechanisms involves
      an immediate sympathetic signal activating the hypothalamic-adrenal medulla
      response and a pituitary signal eliciting a slower adrenocortical response, and
      3) the compensatory sympathetic hyperactivity after panhypopituitarism contribute
      to enhance both the adrenal enzyme basal activity and the hypothalamic and
      adrenal hyperresponse to cold stress.

PMID- 1986944
TI  - Characterization of glucose transporter-enriched membranes from rat skeletal
      muscle: assessment of endothelial cell contamination and presence of sarcoplasmic
      reticulum and transverse tubules.
AB  - The subcellular origin of membranes from rat skeletal muscle that contain insulin
      responsive glucose transporters was investigated. Rat skeletal muscle membranes
      were prepared by isopycnic centrifugation in sucrose gradients. In vivo insulin
      treatment increased the content of GLUT-4 glucose transporters in the 25% sucrose
      fraction (enriched in the plasma membrane marker 5'-nucleotidase) and decreased
      it in the 35% sucrose fraction (devoid of plasma membrane markers). The
      possibility of endothelial cell membrane contamination in these fractions was
      investigated using a mouse monoclonal antibody, MRC OX-43, raised against a cell
      surface protein specific to rat vascular endothelium. MRC OX-43 did not react
      with any of the muscle membrane fractions, but did recognize a protein of around
      100 kDa in extracts of human endothelial cells and rat aorta. An antibody to the
      dihydropyridine receptor of skeletal muscle, IIC12, was used to determine the
      presence of transverse tubules in these fractions. IIC12 reacted positively with
      a 180-kDa protein in purified rat transverse tubules. In contrast, this antibody
      did not cross-react with the 25% or 35% sucrose fractions. The 25% sucrose
      fraction was devoid of calsequestrin and ryanodine receptor, cisternal
      sarcoplasmic reticulum markers. However, small amounts of these proteins were
      detected in the 35% sucrose fraction. The results suggest that the 25% sucrose
      fraction represents plasma membranes, while the 35% sucrose fraction is an
      insulin-sensitive intracellular fraction that contains, but is not enriched in,
      sarcoplasmic reticulum cisternae. The results further show that insulin-induced
      recruitment of GLUT-4 transporters in skeletal muscles can be demonstrated
      independently of GLUT-4 recruitment in endothelial cells.

PMID- 1986945
TI  - Cell-specific expression of the glucocorticoid receptor within granular
      convoluted tubules of the rat submaxillary gland.
AB  - The submaxillary gland, a heterogeneous tissue composed essentially of two
      functionally distinct cell types (tubular epithelial and acinar), offers an
      interesting system in which to study the mechanisms of steroid-dependent growth
      and differentiation. One cell type, the granular convoluted tubular (GCT) cell,
      secretes a large number of physiologically important polypeptides, including
      epidermal and nerve growth factors. Two steroids, androgens and glucocorticoids,
      greatly influence the growth, differentiation, and secretory activity of GCT
      cells. Because glucocorticoids can partially mimic or potentiate androgen
      effects, it has been thought that glucocorticoids act via androgen receptors.
      Since the presence of glucocorticoid receptors is a prerequisite for
      glucocorticoid action, we have investigated the presence and cellular
      distribution of glucocorticoid receptors within the rat submaxillary gland.
      Binding experiments using [3H]dexamethasone revealed the presence of high
      affinity binding sites in rat submaxillary tissue homogenates. Most of these
      sites were specifically competed by dexamethasone, corticosterone, and a pure
      glucocorticoid agonist RU 28362. Neither testosterone nor dihydrotestosterone
      competed for glucocorticoid binding. The cellular distribution of glucocorticoid
      receptors within the submaxillary gland was investigated by immunocytochemistry,
      using two highly specific glucocorticoid receptor antibodies. The receptor was
      localized in the GCT cells, but not in the acinar cells of rat and mouse
      submaxillary tissue sections. In GCT cells, the glucocorticoid receptor
      colocalized with several secretory polypeptides, including epidermal growth
      factor, nerve growth factor, alpha 2u-globulin, and atrial natriuretic factor.
      These data suggest that the submaxillary gland is a target for glucocorticoid
      action and that at least part of the glucocorticoid effects on this tissue are
      mediated by bona fide glucocorticoid receptors.

PMID- 1986946
TI  - Differential development of angiotensin II receptor subtypes in the rat brain.
AB  - Angiotensin II receptors in selected brain areas were characterized into two
      distinct subtypes by displacement with specific antagonists. The receptor
      subtypes had different developmental patterns. Type-1 receptors, selectively
      displaced by the specific angiotensin antagonist DuP-753, were predominant in
      adult (8-weeks-old) rats. Type-2 receptors were selectively displaced by CGP
      42112 A and were expressed remarkably in young (2-weeks-old) rats.

PMID- 1986947
TI  - Insulin administration in vivo increases 1,2-diacylglycerol in rat skeletal
      muscle.
AB  - Based on in vitro studies, an insulin-mediated increase in muscle 1,2
      diacylglycerol (DAG) content has been proposed as a signal for the insulin
      induced stimulation of glucose transport. A recent study [Turinsky, J., Bayly,
      B.P. and O'Sullivan, D.M. (1990) J. Biol. Chem. 265, 7933-7938] challenged this
      hypothesis because no increase in muscle 1,2-diacylglycerol was observed after in
      vivo infusions of insulin at doses which markedly stimulated muscle glucose
      transport. We observed a 30-45% increase in DAG in rat gastrocnemius and
      diaphragm muscles, 5-15 min after intramuscular or intravenous injections of 1-3
      U of insulin per rat, doses which would be expected to activate insulin receptors
      more fully. The effects on DAG were similar whether or not hypoglycemia was
      prevented by co-injection of glucose.

PMID- 1986948
TI  - Progestin receptor cells in the 8-day-old male and female mouse cerebral cortex:
      autoradiographic evidence for a sexual dimorphism in target cell number.
AB  - The present study examined the number and distribution of progestin receptor
      cells in the 8-day-old male and female cortex and compared cortical labeling with
      that in the preoptic area and central hypothalamus. Eight-day postnatal mice
      (four males and four females), treated with estradiol, were each sc injected with
      0.32 micrograms/100 g BW [125I]progestin (SA, 2200 Ci/mM). Brains were frozen 2 h
      after injection of [125I]progestin, sectioned, and processed for thaw-mount
      autoradiography. Cells with a nuclear concentration of radioactivity were
      localized in lamina VI of the lateral cortical regions of the male and female
      brain, while only a few cortical cells were seen in laminae II, III, and V of the
      suprarhinal, lateral, and cingulate/paracingulate regions. Comparison of the
      number of labeled cells revealed that the female cortex contained significantly
      more labeled cells than the male at three of the four levels investigated.
      Similarly, the number of target cells was higher in the female medial preoptic
      nucleus, but not in the arcuate nucleus and ventromedial hypothalamic nucleus,
      while the distributions of labeled cells in the male and female
      preoptic/hypothalamic regions were comparable. Injection of unlabeled
      progesterone or R5020 1 h before [125I]progestin reduced the nuclear
      concentration of radioactivity in all target regions and verified the specificity
      of [125I]progestin for the progestin receptor. The results of these studies
      indicate that mouse 8-day-old cortex and preoptic area in the female animal have
      more progestin receptor cells than those in the male and demonstrate that
      progestin receptor cells are localized in a region of the cortex known to contain
      few estrogen target cells. These results further suggest that a sexual dimorphism
      in progestin cell number may result in a differential effect of progestin on the
      cortex and preoptic area of the mouse, perhaps establishing a dimorphism in
      development and function.

PMID- 1986949
TI  - Psychosocial distress and infertility: men and women respond differently.
AB  - The purpose of this study was to evaluate gender differences in psychosocial
      responses of 449 consecutive first-admission couples in a fertility clinic.
      Consistent with previous research, infertile women showed higher distress than
      their partners on a global measure of psychiatric symptoms and subscales of
      anxiety, depression, hostility, and cognitive disturbances, as well as on
      measures of stress and self-esteem. When compared with same-sexed population
      norms on the measure of psychiatric symptoms, both male and female infertile
      patients were significantly more distressed than average. No evidence was found
      for unusually high levels of marital or sexual distress at intake. Implications
      of results for clinical management are explored.

PMID- 1986950
TI  - Pregnancy after in vitro fertilization of human follicular oocytes collected from
      nonstimulated cycles, their culture in vitro and their transfer in a donor oocyte
      program.
AB  - This study describes the results with immature human follicular oocytes harvested
      from unstimulated ovaries, matured in vitro, fertilized, and transferred to an
      agonadal recipient. Two hundred seventy immature oocytes were aspirated from 23
      ovaries removed for various gynecological indications from August 1988 to October
      1989. The numbers of follicular oocytes collected from ovaries were compared by
      patients' ages and the stages of menstrual cycle. Immature oocytes in vitro were
      incubated with either mature follicular fluid (FF) or fetal cord serum (FCS). The
      maturation rate in the mature FF group was 55.8%, significantly higher than the
      35.9% in the FCS group. In addition, mature FF group was shown to provide a
      significantly higher fertilization rate than the FCS group (81.0% versus 31.6%).
      More fertilized eggs developed into normal embryos in the nonstimulated cycle
      group than in stimulated cycles with routine treatment. Finally, five embryos
      were transferred to a woman with premature ovarian failure on day 18 of a steroid
      replacement cycle. She subsequently delivered healthy triplet girls. These
      results suggest that in vitro maturation of immature oocytes from unstimulated
      ovaries with mature follicular fluid could be used successfully in a donor oocyte
      program after in vitro fertilization.

PMID- 1986951
TI  - The window of embryo transfer and the efficiency of human conception in vitro.
AB  - Women with ovarian failure transferred with donated oocytes provide a unique in
      vivo model for the elucidation of the window of implantation and efficiency of
      reproduction in the human. Throughout 52 ovum donation cycles, the temporal
      window of endometrial receptivity was tested by replacing 2- to 12-cell embryos
      between days 16 and 24 of hormonally and histologically defined cycles. Of 37
      transfers within days 17 to 19, 15 (40.5%) conceptions occurred. Twelve (32.4%)
      have reached viability. Of 11 patients transferred on days greater than or equal
      to 20, none conceived. Likewise, no pregnancies were achieved with 4 transfers on
      cycle day 16. Analysis of multiple embryo transfers within the suggested window
      of endometrial receptivity (days 17 to 19) revealed 14 of 24 (58.3%) to be
      conception cycles. considering only transfers with two or more embryos, at least
      one of which is of high quality (grades 1 to 2), yielded a 63.2% pregnancy rate.
      The results indicate a very high efficiency for in vitro fecundity provided
      optimal conditions are attained. The concepts leading to success in the ovum
      donation model should set the course for continued research toward improving
      results in other forms of assisted reproduction.

PMID- 1986953
TI  - In vitro fertilization-embryo transfer (IVF-ET) in the United States: 1989
      results from the IVF-ET Registry. Medical Research International, Society for
      Assisted Reproductive Technology, The American Fertility Society.
AB  - This is the fourth annual report of the United States Registry of in vitro
      fertilization-embryo transfer (IVF-ET) and related practices. The present report
      describes the 1989 experiences of 163 United States member clinics with respect
      to treatments and outcomes. During 1989, the clinics reported performing 24,183
      ovarian stimulation cycles. From all treatments, including frozen ET and IVF with
      donor oocytes, there were with 4,598 clinical pregnancies and 3,472 live
      deliveries. Ninety-eight percent of the clinics had at least one delivery, and
      overall a total of 4,736 babies were born. The overall live delivery rates were
      14% for IVF (based on 15,392 retrievals), 23% for gamete intrafallopian transfer
      (GIFT) (based on 3,652 retrievals), 26% for IVF and GIFT in combination (based on
      452 retrievals), and 17% for zygote intrafallopian transfer (ZIFT) and related
      practices (based on 908 retrievals). In addition to these treatments, results are
      presented for frozen ETs and IVF of donated oocytes.

PMID- 1986952
TI  - Evaluation of luteal support therapy in a randomized controlled study within a
      gamete intrafallopian transfer program.
AB  - A randomized controlled study of luteal support therapy (using intramuscular
      injections of progesterone and/or human chorionic gonadotropin) was conducted in
      a trial designed to minimize variables that might adversely affect the change of
      pregnancy. After applying rigid selection criteria, 207 women were recruited into
      one of four groups. Mathematical modeling was applied to the results to determine
      if there were degrees of improvement in uterine receptivity relative to various
      grades of embryo quality ("E" factor). Although the trial size was insufficient
      to enable the detection of significant improvements in the pregnancy rates that
      ranged from 27.5% for non-treatment to 41.2% for those receiving combined
      treatment, the birth rates were significantly better with luteal support (11.8%
      versus 29.4%). Similarly, the overall implantation rate just failed to reach
      statistical significance for luteal support, but the ongoing implantations were
      significantly better (3.6% versus 9.0%). Data modeling indicated that luteal
      support, particularly with the combined regimen, could improve the ongoing
      implantation rate by up to 2.5-fold when the E factor was poorest.

PMID- 1986954
TI  - Handling of tubal infertility after introduction of in vitro fertilization:
      changes and consequences.
AB  - This study aimed at quantifying some important social and economic consequences
      of the altered handling of tubal infertility after the establishment of IVF
      treatment. The number of tubal operations was reduced by 50%. This had most
      important and positive implications on the availability of the operating theater
      for other elective operations, on the availability of hospital beds for other
      patient groups, and on the total duration of the certificate of illness. The
      calculated costs per live birth were $17,000 after tubal surgery, compared with
      $12,000 after IVF treatment. Life table analyses demonstrated a highly
      significant increased rate of deliveries after a complete IVF treatment (72.3%
      per patient) compared with tubal surgery (23.7%, P less than 0.001).

PMID- 1986955
TI  - Young's syndrome (obstructive azoospermia and chronic sinobronchial infection): a
      quantitative study of axonemal ultrastructure and function.
AB  - The ultrastructure and function of nasal cilia and sperm tails were examined in
      23 men with Young's syndrome and compared with data previously collected from 10
      normal subjects. Quantitative electron microscopic assessment showed that sperm
      tails from patients with Young's syndrome contained significantly fewer central
      pair microtubules, radial spokes, and inner dynein arms, and their cilia
      contained less inner dynein arms than normal subjects. The Young's syndrome
      patients had normal in vitro ciliary beat frequency (11.4 +/- 0.9 Hz), and 12 of
      the 23 had normal nasal mucociliary clearance (15.0 +/- 5.0 minutes). However,
      the remaining 11 had markedly abnormal nasal mucociliary clearance in vivo. In
      these patients, the deficiency of ciliary inner dynein arms did not appear to
      affect ciliary function in vitro but may under mucus loading lead to abnormal in
      vivo ciliary function. The consistent abnormalities shown in cilia and sperm
      tails, though apparently minor, constitute a common factor in both the
      reproductive and respiratory tracts which may, in combination with abnormalities
      in the in vivo environment, lead to the features of Young's syndrome.

PMID- 1986956
TI  - Study of bilateral histology and meiotic analysis in men undergoing varicocele
      ligation.
AB  - Fifty men underwent testicular biopsy at the time of varicocele ligation. The
      biopsies were scored and also a portion from each biopsy was subjected to meiotic
      analysis. All men were followed up (mean follow-up 19.3 months). There were no
      consistent histologic or meiotic abnormalities, and there was no evidence that
      the varicocele side was more defective than the contralateral side. Thirteen
      pregnancies were recorded, and these occurred only when the mean Johnsen score
      from one or other testis was greater than 6.0.

PMID- 1986957
TI  - The effects of three serotypes of Ureaplasma urealyticum on spermatozoal motility
      and penetration in vitro.
AB  - The effects of incubation of spermatozoa with three serotypes of Ureaplasma
      urealyticum on spermatozoal motility and penetration in vitro were investigated.
      Using computer-assisted video microscopy, three parameters of motility were
      determined: individual path lengths, individual vectorial distances, and
      percentage motility. Polyacrylamide gels were used as a medium for assessment of
      spermatozoal penetration. Ureaplasma-infected spermatozoa did have significantly
      greater path lengths and individual distances than did uninfected controls, but
      ureaplasma infection had no significant effect on percentage motility. Overall,
      there were no significant differences in penetration distances between ureaplasma
      infected spermatozoa and their corresponding uninfected controls. Our conclusion
      is that the ureaplasmas did not adversely affect motility or penetration when
      spermatozoa were incubated with ureaplasmas for 45 minutes at ureaplasma:sperm
      ratios as high as 100:1.

PMID- 1986958
TI  - A procedure for cryopreservation of hamster oocytes yielding highly conserved
      oocytes suitable for sperm penetration tests.
AB  - Hamsters were superovulated and their oocytes frozen in Dulbecco's phosphate
      buffered saline containing 10% fetal calf serum and 1.5 molar 1,2-propanediol. In
      several experiments, 94% of the hamster oocytes survived freezing and were
      equivalent to fresh oocytes in sperm penetration. In routine use of the procedure
      described, also 94% of 1,340 frozen-thawed oocytes were satisfactory for sperm
      penetration of several species. Frozen oocytes eliminate problems and costs of
      maintaining hamster colonies with variable responses on individual days.

PMID- 1986959
TI  - Microsurgical epididymovasostomy by tubule intussusception: a new technique in
      rat model.
AB  - This experimental study on 15 adult male rats with bilateral epididymovasostomies
      evaluates a new technique of tubule intussusception as an improved form of end-to
      end anastomosis. This paper describes in detail the steps in this technique and
      offers physiological, anatomical, and histological follow-up after 3 months. With
      this technique there is a 97% patency rate and a 23.3% incidence of macroscopic
      spermatic granuloma. Complications are discussed in detail.

PMID- 1986960
TI  - Influence of growth factors in defined culture medium on in vitro development of
      mouse embryos.
AB  - Two-cell mouse embryos were cultured in Ham's F-10 medium (Gibco, Grand Island,
      NY) supplemented with various concentrations of transferrin, insulin, epidermal
      growth factor, platelet-derived growth factor, or fibroblast growth factor. Rates
      of development and the cell numbers per blastocyst were compared between embryos
      cultured in Ham's F-10 alone versus growth factor (GF) supplemented media. Rates
      of development in the presence of GF were inhibited significantly in some cases,
      and the cell numbers per blastocyst were identical in all groups. When compared
      with in vivo derived blastocysts, however, all in vitro cultured embryos had
      significantly less cells per embryo. These results suggest that GF
      supplementation of media for culture of early preimplantation embryos does not
      stimulate the rate of embryonic development in vitro.

PMID- 1986961
TI  - Fertility before and after surgery for primary ovarian pregnancy.
AB  - Primary ovarian pregnancy usually occurs in parous fertile women. It is an
      accidental event probably related to the presence of the IUD affecting
      implantation rather than an indicator of altered fertility. Reproductive
      performance postoperatively remains unmodified.

PMID- 1986962
TI  - The relationship between follicle diameter, fertilization rate, and microscopic
      embryo quality.
AB  - The diameter of preovulatory ovarian follicles was measured at the time of
      transvaginal US-guided oocyte retrieval, and the oocytes were subsequently
      examined to assess fertilization rates and the quality of developing embryos.
      With follicles divided into three groups of increasing diameter, there were no
      significant differences in the fertilization rates of oocytes recovered from
      follicles of different size. Embryo quality improved with increasing follicle
      size, although the differences were not highly significant. Our results
      demonstrate that an acceptable laboratory outcome can be achieved with oocytes
      retrieved from smaller sized follicles.

PMID- 1986964
TI  - The concentrations of transferrin, beta 2-microglobulin, and albumin in seminal
      plasma in relation to sperm count.
AB  - A number of studies have shown a relationship between transferrin levels in
      seminal plasma and sperm count. In the present study, the levels of transferrin,
      beta 2-microglobulin and albumin were measured in 171 samples of seminal plasma
      (50 subjects with normal sperm count; 32 with azoospermia; 49 with
      oligozoospermia; 10 with polyzoospermia; and 31 vasectomized). All three proteins
      were related to sperm count. It is concluded that there is a general relationship
      between seminal plasma proteins and sperm numbers and that some products of the
      sperm themselves must control the entry of plasma proteins into seminal plasma.

PMID- 1986963
TI  - Edwards' syndrome after the replacement of cryopreserved-thawed embryos.
AB  - A case of Edwards' syndrome after the replacement of frozen-thawed embryos is
      reported. The presence of cardiac abnormalities and limb deformities raised the
      suspicion of chromosomal abnormality. The diagnosis of trisomy 18 was made by
      cytogenetic analysis of fetal blood from the umbilical vein. The chromosomal
      nondisjunction might have been spontaneous or because of freezing and thawing. If
      it occurred as a result of freezing and thawing, it is more likely that this was
      at the first cleavage division rather than the second meiotic division because
      the embryos were frozen at the late pronuclear stage. Unfortunately, there were
      no karyotypic markers in the couple's chromosomes to time the nondisjunction. The
      wisdom of using donor oocytes in an ovum donation program from patients with long
      standing infertility is questioned.

PMID- 1986965
TI  - Prevention of ovarian hyperstimulation syndrome.

PMID- 1986966
TI  - Peritoneal seeding of endometrial cells--risky?

PMID- 1986967
TI  - Immunomodulation with pentoxifylline abrogates macrophage-mediated infertility in
      an in vivo model: a paradigm for a novel approach to the treatment of
      endometriosis-associated subfertility.
AB  - Although present consensus holds that endometriosis-associated subfertility is
      the result of an adverse effect of hyperactivated macrophages on early
      reproductive events, most treatments for endometriosis are directed at the
      suppression of endometriotic implants. We hypothesized that periovulatory
      immunomodulation of macrophage activation and inflammatory mediator production
      might be a more effective approach to this problem. In this experiment,
      heterologous transfer of activated peritoneal inflammatory cells within a
      syngeneic strain of mice was used as an in vivo model for the peritoneal
      inflammatory environment of the endometriosis patient. Intraperitoneal transfer
      of hyperactivated macrophages, but not basal state macrophages, significantly
      inhibited fertilization. This activity was reversed by periovulatory
      pentoxifylline treatment. Immunomodulation of peritoneal inflammatory cell
      hyperactivation with pentoxifylline may represent a new modality for the
      treatment of endometriosis-associated subfertility.

PMID- 1986968
TI  - Endometrial histology after first trimester spontaneous abortion.
AB  - The endometrial histology after spontaneous abortion was investigated by
      performing an endometrial biopsy in the two menstrual cycles subsequent to
      miscarriage in 12 women. In the first cycle, 66% (8/12) of the biopsies had the
      following abnormalities: (1) proliferative endometrium (n = 4), (2) proliferative
      glands and decidualized stroma (n = 1), (3) endometritis (n = 1), and (4) luteal
      insufficiency (n = 2). In the second cycle, 20% (2/10) of the biopsies
      demonstrated luteal insufficiency. Forty-five percent (10/22) of the first two
      cycles after spontaneous abortion demonstrated abnormal endometrial histology,
      with the first appearing more abnormal than the second (P = 0.06). Two
      conceptions occurred during the study period; both were uneventful term
      pregnancies. These findings suggest that a large proportion of the first two
      menstrual cycles after spontaneous abortion and curettage are abnormal, with the
      first cycle being more frequently abnormal than the second.

PMID- 1986969
TI  - Micromanipulation in a center for reproductive medicine.
AB  - Several variations of micromanipulation of the female gamete (zona drilling, zona
      cracking, ooplasmic sperm injection, partial zona dissection) have been applied
      recently to human IVF to overcome severe male factor. Of the first 16 cycles
      attempted using partial zona dissection, one pregnancy resulted leading to a
      normal term delivery. Careful removal of the coronal cells, as well as stepwise
      removal of sucrose postpartial zona dissection, will facilitate this procedure
      and greatly reduce potential damage to the oocyte by pH, mechanical, or thermal
      injury. Micromanipulation has become a routine service offered in our program in
      cases where the likelihood of a poor IVF outcome is either known or suspected,
      and also serves as a replacement for simple reinsemination in cases of failed
      fertilization.

PMID- 1986970
TI  - Oocyte and pre-embryo donation to women with ovarian failure: an extended
      clinical trial.
AB  - The outcome of a series of pre-embryo transfers to 31 women with ovarian failure
      is described. Twenty six fertile women functioned as nonanonymous donors,
      providing oocytes for in vitro fertilization after undergoing controlled ovarian
      hyperstimulation and transvaginal ultrasound directed oocyte aspiration.
      Recipients, 24 to 44 years of age, received hormone replacement therapy before
      pre-embryo transfer (ET). A mean of 13.7 +/- 1.1 oocytes were obtained per
      aspiration resulting in the transfer of 4.5 +/- 0.2 pre-embryos to each recipient
      couple. Twenty-five of 47 ET resulted in pregnancy (53.2% per ET); 5 preclinical,
      and 20 clinical, of which 18 are ongoing or delivered. The overall implantation
      rate per individual transferred fresh pre-embryo was 21.1%. We conclude that
      oocyte donation is a safe and highly efficient means of achieving pregnancy for
      women with ovarian failure.

PMID- 1986971
TI  - Preovulatory follicular fluid steroid levels in stimulated and unstimulated
      cycles triggered with human chorionic gonadotropin.
AB  - The purpose of this study was to analyze follicular fluid (FF) samples for
      steroid levels from stimulated and unstimulated cycles triggered with human
      chorionic gonadotropin (hCG) and to assess the influence of controlled ovarian
      hyperstimulation and luteinizing hormone/hCG on these levels. Spontaneous
      ovulatory cycles were monitored with serial ultrasound examinations, and hCG
      10,000 IU was given when the lead follicle was mature. Fourteen FF samples
      yielding fertilizable oocytes were compared with 13 FF samples from controlled
      ovarian hyperstimulation cycles. Progesterone (P) was higher in controlled
      ovarian hyperstimulation than in unstimulated cycles (9.0 +/- 1.2 micrograms/mL
      versus 4.4 +/- 0.6 microgram/mL; mean +/- SEM), whereas estradiol (E2) was lower
      (0.8 +/- 0.1 microgram/mL versus 1.3 +/- 0.2 microgram/mL), resulting in a higher
      P:E2 ratio (15.5 +/- 3.3 versus 4.4 +/- 0.7). Androstenedione (A), testosterone
      (T), and T:E2 ratios were all higher in unstimulated than controlled ovarian
      hyperstimulation cycles. We conclude that controlled ovarian hyperstimulation is
      associated with increased FF P, decreased FF E2, T, and A levels, and decreased
      T:E2 ratios, suggesting altered steroidogenesis and enhanced follicular aromatase
      activity.

PMID- 1986972
TI  - The effect of bromocriptine on the motility of human spermatozoa and its capacity
      to penetrate the cervical mucus.
AB  - We investigated the direct effects of bromocriptine on the motility of the human
      ejaculated spermatozoa and its capacity to penetrate the cervical mucus (CM) in
      vitro. Washed sperm were incubated with a wide range of bromocriptine
      concentrations (0.005 to 5 mM). Progressive and total motility was evaluated
      after 15, 30, 60, and 180 minutes. No reduction of motility was observed at any
      concentration tested. Similar results were observed with semen samples. Failure
      to alter sperm motility was evident in samples with either good or reduced
      motility. Also, CM penetration as measured after 90 minutes by Penetrak assay
      (Serono Diagnostics, Randolph, MA) was not impaired by a concentration as high as
      5 mM bromocriptine. We conclude that bromocriptine in a wide range of
      concentrations does not inhibit sperm motility nor does it impair the capability
      of the sperm to penetrate the CM. These data support the therapeutic use of daily
      vaginal bromocriptine for the treatment of infertility.

PMID- 1986973
TI  - Treatment of tubal ectopic pregnancy by salpingotomy with or without tubal
      suturing and salpingectomy.
AB  - Thirty-four women with unruptured tubal ectopic pregnancy (EP) were randomly
      assigned to undergo salpingotomy without tubal suturing (n = 15) or salpingotomy
      with tubal suturing (n = 19). The reproductive performance of these patients was
      compared with 24 patients who underwent salpingectomy for their EP (historical
      control). Using life table analysis, the cumulative probability of intrauterine
      pregnancy (IUP) at 12 and 24 months was 45% and 45% after salpingotomy without
      tubal suturing and 21% and 47% after salpingotomy with tubal suturing,
      respectively. The cumulative probability of IUP after salpingectomy (21% and 26%
      at 12 and 24 months, respectively) was significantly lower than after
      salpingotomy with or without tubal suturing. There was no difference in the
      cumulative probability of EP after salpingotomy with or without tubal suturing,
      but it was significantly higher than after salpingectomy. In 18 women who
      subsequently underwent laparoscopy or laparotomy, no significant difference was
      found between the degree of adhesions after salpingotomy with or without tubal
      suturing. These findings suggest that IUP after conservative treatment is higher
      than after salpingectomy, but recurrent EP is also higher. Intrauterine pregnancy
      occurs earlier after salpingotomy without tubal suturing than after salpingotomy
      with tubal suturing. This might be because of rapid return of tubal function
      after healing by secondary intention.

PMID- 1986974
TI  - Ovarian hyperandrogenism: the role of and sensitivity to gonadotropins.
AB  - To determine if ovarian hyperandrogenism represents enhanced gonadotropic
      stimulation, augmented ovarian sensitivity to gonadotropins, or both, we have
      undertaken to evaluate (1) the 24-hour integrated concentrations of serum total
      testosterone (T) and luteinizing hormone (LH) and (2) the ovarian response of T
      to exogenous gonadotropic stimulation. To this end, two groups of women,
      hyperandrogenic anovulatory (n = 4) and early follicular phase (n = 4) normally
      cycling controls, were subjected to continuous blood withdrawal over 24 hours
      with a portable Cormed pump (Cormed Inc., Middleport, NY) and to exogenous
      stimulation with human chorionic gonadotropin. Our current observations support
      the notion that ovarian hyperandrogenism represents the combined impact of an
      overall increase in gonadotropic support coupled with augmented ovarian
      sensitivity to gonadotropic stimulation.

PMID- 1986975
TI  - Endometrial antibodies versus CA-125 for the detection of endometriosis.
AB  - Detection of endometrial antibodies using an indirect immunofluorescence method
      along with a well-established human endometrial carcinoma cell line was evaluated
      and compared with CA-125 for detecting endometriosis. Two hundred two patient
      sera from the infertility, gynecological, and gynecological oncology services
      were evaluated. The sensitivity for antibody testing was 83.1% with a specificity
      of 78.8%, in contrast to a sensitivity of 27.3% and a specificity of 82.6% for CA
      125. These preliminary findings offer promise that antibody detection methods may
      be a useful adjunct in the diagnosis of endometriosis.

PMID- 1986976
TI  - Maturation of immature oocytes by coculture with granulosa cells.
AB  - To increase the number of embryos available for transfer, immature human oocytes
      were cocultured with granulosa cells from preovulatory follicles. Greater numbers
      of immature oocytes incubated with granulosa cells had dispersion of the cumulus
      and corona cells compared with immature oocytes cultured in media alone. Fifty
      four percent of immature oocytes were fertilized after coculture with granulosa
      cells compared with 20% fertilization of immature oocytes cultured without
      granulosa cells. There were no cases in which only embryos developed from
      immature oocytes were transferred, and thus we could not determine if the
      immature oocytes could contribute to a pregnancy.

PMID- 1986977
TI  - A prospective study of sodium-lithium countertransport and hypertension in Utah.
AB  - A 7-year prospective study of a cohort of 1,458 normotensive adults from Utah
      pedigrees, screened from 1980 to 1985, was done to determine whether baseline
      levels of sodium-lithium countertransport were associated with an increased risk
      of future hypertension. Subsequent new hypertension (n = 39) was ascertained in
      1989 from detailed follow-up medical questionnaires (67% response). Previous
      segregation analyses on a subset of these pedigree members who responded (n =
      342) using family relationships in addition to countertransport levels have shown
      statistically inferred major gene segregation of sodium-lithium countertransport
      levels. In the normotensive adults inferred by segregation analysis to carry the
      recessive major gene for high sodium-lithium countertransport, new-onset
      hypertension occurred in 18.8% (3 of 16) compared with 3.7% (12 of 326) in the
      low sodium-lithium countertransport genotype group (relative risk, 4.6 [1.6,
      13.9]; p = 0.03). However, an elevated baseline sodium-lithium countertransport
      level without genotype information from segregation analysis did not increase the
      risk of future hypertension in the complete cohort of adult pedigree members
      (relative risk, 1.02 [0.85, 1.22]). Adjustment for other risk factors reduced the
      relative risk to 0.90 (0.72, 1.11). We conclude that the presence of a major gene
      for sodium-lithium countertransport or another closely linked gene, rather than
      the actual level of sodium-lithium countertransport, may increase the risk of
      hypertension onset. High sodium-lithium countertransport levels do not increase
      the risk of future hypertension for individuals in whom only polygenic and
      environmental effects determine sodium-lithium countertransport level.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1986978
TI  - A potent vasoconstrictor in the rat submandibular gland.
AB  - We detected a novel vasoconstrictor in an arginine esterase fraction separated
      from fractions containing tonin and other esterases that were obtained from a rat
      submandibular gland extract. When tested on isolated rabbit aorta rings, the
      substance caused dose-related contractions that were slow in onset, long-lasting,
      and difficult to reverse by rinsing. The substance acts directly on vascular
      smooth muscle, since preincubation with plasma or intact endothelium is not
      required. The fact that the constrictor was destroyed by heat and incubation with
      pronase suggests that it is a protein. Molecular sieving indicates an estimated
      molecular weight of 24,000 Da. It has a neutral isoelectric point that is higher
      than the pI of tonin, from which it can be separated by anion exchange
      chromatography. A small amount of the vasoconstrictor was obtained by gel
      filtration and eluted from isoelectric focusing polyacrylamide gels. The purified
      substance showed a single band on sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. It was a potent vasoconstrictor; an estimated concentration of
      2.5 nM induced contraction of isolated rabbit aorta rings ranging from 15% to 40%
      of the maximum contraction obtained by 60 mM KCl. Contraction was completely
      blocked by 1 mM (p-amidinophenyl)methanesulfonyl fluoride, a serine protease
      inhibitor. Contractile activity was not affected by hirudin, a thrombin
      inhibitor, but was completely inhibited by soybean trypsin inhibitor and blunted
      by aprotinin; thus it may be a trypsin-like serine protease. Purified
      vasoconstrictor preparation showed hydrolyzing activity on Pro-Phe-Arg-methyl
      coumarin amide, a kallikrein substrate. We conclude that a novel vasoconstrictor
      serine protease is present in the rat submandibular gland.

PMID- 1986979
TI  - High-normal blood pressure progression to hypertension in the Framingham Heart
      Study.
AB  - This study sought to determine if individuals with high-normal blood pressure
      (diastolic blood pressure of 85-89 mm Hg) progress to hypertension more
      frequently than those with normal blood pressure (diastolic blood pressure less
      than 85 mm Hg), thus advancing to a higher cardiovascular risk category.
      Individuals from the Framingham Heart Study were placed in normal and high-normal
      blood pressure categories and followed for 26 years for the development of
      hypertension. With hypertension defined as a diastolic blood pressure of 95 mm Hg
      or greater or the initiation of antihypertensive therapy, 23.6% of men and 36.2%
      of women with normal blood pressure developed hypertension compared with 54.2% of
      men and 60.6% of women with high-normal blood pressure. The relative risk for the
      development of hypertension associated with high-normal blood pressure was 2.25
      for men (95% confidence interval [CI], 1.8-2.8; p less than 0.0001) and 1.89 for
      women (95% CI, 1.5-2.3; p less than 0.0001). The age-adjusted relative risks
      estimated by the proportional hazards model were 3.36 for men and 3.37 for women
      (p less than 0.001). Among those risk factors examined, baseline systolic and
      diastolic blood pressure, Metropolitan relative weight, and change in weight over
      time were significant predictors of future hypertension in men and women whose
      initial blood pressure was normal. For men with high-normal blood pressure,
      systolic blood pressure and change in weight were identified as risk factors for
      future hypertension. These results indicate that the probability of individuals
      with blood pressure in the high-normal range developing hypertension is twofold
      to threefold higher than in those with normal blood pressure.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1986980
TI  - Effects of chronic intraventricular sodium on blood pressure and fluid balance.
AB  - To examine if chronic sodium loading on the brain produces sustained increases in
      blood pressure, water intake, and sodium excretion, hypertonic (0.5 M and 1.5 M)
      and isotonic (0.15 M) NaCl solutions were infused into the third ventricle of
      Sprague-Dawley rats at a rate of 5.5 microliters/hr for 7 days.
      Intracerebroventricular infusion of 1.5 M NaCl significantly increased systolic
      blood pressure during the entire infusion period (+23 +/- 5 mm Hg on day 1 and
      +15 +/- 2 mm Hg on day 7, n = 10, mean +/- SEM). Blood pressure rose
      insignificantly in the 0.5 M NaCl group, whereas it remained at the baseline
      levels in the 0.15 M NaCl group. The increases in water intake (day 2), positive
      water balance (day 2), and negative sodium balance (day 3) were observed in the
      1.5 M NaCl group. On day 7, the 1.5 M NaCl group showed hyponatremia and low
      plasma osmolality and had higher plasma norepinephrine but not vasopressin
      compared with the 0.15 M NaCl group. In another series of study, depressor
      response to intravenous hexamethonium (20 mg/kg) in the 1.5 M NaCl group was
      greater than that in the 0.15 M NaCl group on both day 1 and 7. The depressor
      response to d(CH2)5Tyr(Me)-arginine vasopressin (10 micrograms/kg) in the 1.5 M
      NaCl group was greater on day 1 but not on day 7. These results indicate that
      sustained sodium stimulus on the central nervous system causes mild hypertension
      and alters water and sodium balance. The sympathetic nervous system but not
      vasopressin may play an important role in the chronic phase of central NaCl
      induced hypertension.

PMID- 1986981
TI  - Sympathetic neural adjustments to stress in physically trained and untrained
      humans.
AB  - The purpose of this study was to determine if the state of physical training
      influences sympathetic neural activation during acute stress in humans. We
      recorded muscle sympathetic nerve activity (microneurography of the peroneal
      nerve), arterial blood pressure, and heart rate in 12 highly trained, endurance
      athletes (25 +/- 1 years, mean +/- SEM) and 12 untrained subjects (27 +/- 1
      years) before (supine rest control) and during: 1) lower body negative pressure
      at -5, -10, -15, and -20 mm Hg (orthostatic stress); 2) isometric handgrip at 30%
      of maximum (exercise stress); and 3) hand immersion in ice water, that is, the
      cold pressor test (thermal stress). Body weight was not different in the two
      groups, but the athletes had a lower body fat content (8.9 +/- 1.3% versus 16.1
      +/- 2.0%, p less than 0.05). During supine rest, muscle sympathetic nerve burst
      frequency (24 +/- 3 versus 24 +/- 2 bursts/min, athletes versus untrained
      subjects) and burst incidence (36 +/- 3 versus 44 +/- 4 bursts/100 heart beats)
      and arterial blood pressure were not different in the two groups, but heart rate
      was lower in the athletes (54 +/- 2 versus 67 +/- 3 beats/min, p less than
      0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1986983
TI  - Effect of enalapril treatment on the pressure-natriuresis curve in spontaneously
      hypertensive rats.
AB  - The effect of chronic angiotensin I converting enzyme inhibition on the pressure
      natriuresis relation was studied in Wistar-Kyoto and spontaneously hypertensive
      rats. Enalapril maleate (25 mg.kg-1.day-1 in drinking water) was started at 4-5
      weeks of age. At 7-9 weeks of age, the pressure-natriuresis relation was studied
      while the rats were under Inactin anesthesia 1 week after the right kidney and
      adrenal gland were removed. Neural and hormonal influences on the remaining
      kidney were fixed by surgical renal denervation, adrenalectomy, and infusion of a
      hormone cocktail (330 microliters.kg-1.min-1) containing high levels of
      aldosterone, arginine vasopressin, hydrocortisone, and norepinephrine dissolved
      in 0.9% NaCl containing 1% albumin. Changes in renal function resulting from
      alterations in renal artery pressure were compared between enalapril-treated and
      control rats. Mean arterial pressure (+/- SEM) under anesthesia was 118 +/- 5, 94
      +/- 4, 175 +/- 3, and 124 +/- 2 mm Hg for control Wistar-Kyoto (n = 10),
      enalapril-treated Wistar-Kyoto (n = 10), control spontaneously hypertensive (n =
      9), and enalapril-treated spontaneously hypertensive (n = 9) rats, respectively.
      When renal artery pressure was set at values above approximately 125 mm Hg,
      control spontaneously hypertensive rats excreted less sodium and water than
      control Wistar-Kyoto rats. Enalapril treatment resulted in a significant and
      similar shift to the left of the pressure-natriuresis relation in both strains of
      rats so that a lower renal artery pressure was required to excrete a similar
      amount of sodium when compared with their respective untreated controls.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1986982
TI  - Renal manifestations of NaCl sensitivity in borderline hypertensive rats.
AB  - Compared with the normotensive Wistar-Kyoto rat, the spontaneously hypertensive
      rat exhibits exaggerated alterations in renal sympathetic nerve activity and
      excretory function during volume expansion (exaggerated natriuresis) and
      environmental stress (antinatriuresis). The borderline hypertensive rat is the
      first filial offspring of the spontaneously hypertensive rat and the Wistar-Kyoto
      rat and develops hypertension with increased dietary NaCl intake. The present
      investigation sought to determine whether the dietary NaCl intake-induced
      transition from the normotensive state of the Wistar-Kyoto parent to the
      hypertensive state of the spontaneously hypertensive parent in the borderline
      hypertensive rat was accompanied by a similar transition of the renal sympathetic
      nerve activity and excretory responses to volume expansion and environmental
      stress. Borderline hypertensive rats fed a 1% NaCl diet remained normotensive and
      exhibited renal sympathetic nerve activity and excretory responses to volume
      expansion and environmental stress that were similar to those of their Wistar
      Kyoto parent. Borderline hypertensive rats fed an 8% NaCl diet developed
      hypertension and exhibited responses that were similar to those of their
      spontaneously hypertensive parent. Thus, the dietary NaCl intake-induced
      transition from the normotensive state of the Wistar-Kyoto parent to the
      hypertensive state of the spontaneously hypertensive parent in the borderline
      hypertensive rat was accompanied by a similar transition of the renal sympathetic
      nerve activity and excretory responses to volume expansion and environmental
      stress. The results suggest that increased dietary NaCl intake is able to induce
      or unmask the capabilities for these responses, which are genetically conveyed to
      the borderline hypertensive rat by the spontaneously hypertensive rat parent in
      latent forms.

PMID- 1986984
TI  - Rapid baroreceptor resetting in chronic hypertension. Implications for
      normalization of arterial pressure.
AB  - The purpose of this study was to examine the ability of baroreceptors of renal
      hypertensive rabbits to reset rapidly during acute changes in arterial pressure.
      The carotid sinus (CS) was vascularly isolated and baroreceptor activity was
      recorded during slow ramp increases in CS pressure in hypertensive (one-kidney,
      one wrap; 127 +/- 3 mm Hg) and normotensive (one-kidney, no wrap; 85 +/- 3 mm Hg)
      rabbits anesthetized with chloralose. Control measurements were made after
      holding pressure for 10-15 minutes at the level of arterial pressure recorded
      before each experiment. Baroreceptor threshold pressure (Pth) was higher in
      hypertensives (78 +/- 4 mm Hg) compared with normotensives (55 +/- 3 mm Hg, p
      less than 0.05), and nerve activity was less in hypertensives over a wide range
      of pressure. CS distensibility (sonomicrometers) was not significantly different
      in the two groups. After increasing holding pressure from control by 30 and 60 mm
      Hg for 10-15 minutes, the extent of baroreceptor resetting (delta Pth/delta
      holding pressure x 100%) in normotensives was 39 +/- 6% and 33 +/- 2%,
      respectively, but only 14 +/- 5% and 9 +/- 3% in hypertensives (p less than
      0.05). After decreasing holding pressure by 30 and 60 mm Hg, resetting was
      similar in normotensives (32 +/- 6% and 28 +/- 3%) and hypertensives (34 +/- 3%
      and 30 +/- 4%). In hypertensive rabbits, acute (10-15 minutes) exposure of
      baroreceptors to normotension (71 +/- 4 mm Hg) decreased Pth to 62 +/- 4 mm Hg
      and increased nerve activity to levels not significantly different from those of
      normotensive animals without altering CS distensibility.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1986985
TI  - Aging escalates baroreceptor reflex suppression by the posterior hypothalamus in
      rats.
AB  - To examine whether baroreceptor reflex regulation by the posterior hypothalamus
      becomes modified with age, we compared baroreceptor reflex sensitivity and
      hypothalamic responsiveness in 2- and 10-month-old rats anesthetized with
      urethane-chloralose. Hypothalamic regulation of baroreceptor reflex sensitivity
      was assessed by recording responses to intravenously infused phenylephrine and
      afferent aortic nerve stimulation after sham operation or electrolytic
      destruction of the posterior hypothalamus. Regardless of age, reflex bradycardia
      and sympathoinhibition elicited during pressor responses to phenylephrine, as
      well as all cardiovascular and sympathetic nerve responses to afferent aortic
      nerve stimulation, were stronger in rats with bilateral hypothalamic lesions than
      in age-matched, sham-operated controls. Distinctively, because baroreceptor
      reflex sensitivity differed with age only in sham-operated controls but not in
      lesioned rats, we concluded that age-related differences in baroreceptor reflex
      sensitivity had been abolished by posterior hypothalamic lesions. Other
      experiments were then performed to compare responses to graded electrical
      stimulation of the posterior hypothalamus in baroreceptor-intact rats. Pressor
      and sympathoexcitatory responses to hypothalamic stimulation were larger, and
      stimulus thresholds were lower at 10 than at 2 months of age thereby suggesting
      that hypothalamic responsiveness had increased with age. Our results are in
      accord with the interpretation that aging exacerbates the baroreceptor reflex
      suppression normally exerted by the posterior hypothalamus.

PMID- 1986986
TI  - Protein kinase inhibitors and blood pressure control in spontaneously
      hypertensive rats.
AB  - Considerable evidence suggests that protein kinase C activation participates in
      the regulation of vascular smooth muscle tone. The objective of the current study
      was to examine the relations between inhibition of protein kinase C (PKC) and
      myosin light-chain kinase (MLCK) and vasorelaxation and blood pressure regulation
      in spontaneously hypertensive rats (SHR). Putative PKC inhibitors from two
      chemical classes, staurosporinelike (staurosporine and K252A) and
      isoquinolinesulfonamides (H7 and HA1004), were tested for their ability to 1)
      inhibit PKC and MLCK from SHR aorta, 2) relax isolated SHR aorta, and 3) lower
      blood pressure in conscious SHR. A rank order of potency for the inhibition of
      PKC and MLCK was established, with the staurosporinelike compounds (staurosporine
      PKC IC50 = 54 nM) clearly more potent than the isoquinolinesulfonamides (H7 PKC
      IC50 = 128 microM). The rank order of potency for inhibition of PKC was retained
      for inhibition of MLCK for all compounds. Staurosporine (EC50 = 75 nM) and H7
      (EC50 = 2 microM) caused concentration-dependent relaxation of SHR aorta, but
      only staurosporine produced vasorelaxation at concentrations consistent with the
      inhibition of PKC or MLCK. Dose-dependent reductions in arterial pressure of SHR
      were demonstrated after intravenous injection of staurosporine and HA1004. A
      single intravenous injection of staurosporine (0.3 mg/kg) lowered blood pressure
      for more than 10 hours. Staurosporine also lowered blood pressure after oral
      administration. The depressor response to staurosporine was unaffected by
      sympathetic beta-adrenergic blockade. In conclusion, the vasorelaxant and
      antihypertensive actions of staurosporine in SHR are consistent with the
      inhibition of PKC but could also be equally related to inhibition of MLCK. Not
      all PKC inhibitors produce vasorelaxation and lower blood pressure. Moreover, the
      lack of correlation between in vitro vasodilation and PKC or MLCK inhibition for
      the isoquinolinesulfonamide protein kinase inhibitors H7 and HA1004 suggests that
      these agents do not cause vasorelaxation in SHR by inhibition of these enzymes.

PMID- 1986987
TI  - Methodology of sodium sensitivity assessment. The example of age and sex.
AB  - This article addresses the methodology of sodium sensitivity assessment. There
      have been reports to suggest that a high sodium intake is a cause of elevated
      blood pressure and trials to indicate that a reduction in sodium intake may
      reduce blood pressure that is already high; the implications of these findings
      are discussed. Many studies on sodium sensitivity suffer from what could be
      called the "normal probability fallacy"; without appropriate control conditions,
      an intervention such as sodium restriction may incorrectly be assigned to a more
      pronounced response in a subgroup of the study population. As an example,
      findings are reviewed of age and sex as determinants of a response of blood
      pressure to variations in sodium intake. The limited data available suggest that
      subjects that are older and have higher blood pressure levels seem to benefit
      more from a reduction in sodium intake. In addition, elderly subjects at a high
      dietary sodium intake may have a higher risk of developing hypertension. Findings
      in both nonexperimental and experimental studies tend to support this view.
      Findings on sex differences are less consistent. A systematic approach to the
      assessment of factors and mechanisms responsible for sodium sensitivity in some
      subjects is needed to determine who might benefit most. Until more data are
      available, there is little basis to discriminate sodium-sensitive from sodium
      resistant hypertensive subjects.

PMID- 1986988
TI  - Racial and ethnic modifiers of the salt-blood pressure response.
AB  - The relation between sodium and blood pressure is a centuries-old question. A
      substantial body of epidemiological and experimental data has accumulated that
      strongly implicates NaCl as having a causal role in the genesis of arterial
      hypertension. Prospective studies that have been performed in diverse populations
      that have manipulated NaCl exposure by diet or infusion have repeatedly
      documented an NaCl pressor effect. Further, similar studies in biracial
      populations have also demonstrated a greater prevalence of "salt sensitivity" in
      blacks compared with whites. The reasons for this observation are not entirely
      clear; however, intrinsic or hypertension-induced renal abnormalities that limit
      natriuretic capacity, reduced Na+,K(+)-ATPase pump activity, other membrane ion
      transport disturbances, differential exposure to psychological stressors, greater
      insulin resistance, and dietary factors (reduced Ca+ and K+ intake) have all been
      suggested as possibly playing a role. Salt sensitivity appears to be a widespread
      phenomenon. However, it is critically important to determine what factors account
      for racial differences in salt sensitivity. Moreover, the prevalence of salt
      sensitivity in the general population is unknown. Current definitions of salt
      sensitivity are varied and unidirectional. In comparison with bidirectional
      criteria (blood pressure increase with salt loading and blood pressure decrease
      with salt restriction), they are probably inadequate to identify salt-sensitive
      individuals who manifest less extreme blood pressure change after dietary sodium
      or plasma volume manipulations. More sensitive criteria for diagnosing salt
      sensitivity will facilitate a better understanding of racial and ethnic
      differences in the prevalence of salt sensitivity.

PMID- 1986989
TI  - Biohistory of slavery and blood pressure differences in blacks today. A
      hypothesis.
AB  - Genetic factors are known to play an important role in the variations in blood
      pressure levels. However, genetic factors that explain the higher average blood
      pressure levels of western hemisphere blacks when compared with African blacks
      have not been seriously considered. Because the genetic makeup of a population is
      largely determined by biological and ecological forces in the past, an
      examination of the biohistory of blacks, specifically the slavery era, was
      conducted. An overview of the salient findings of that investigation is included
      in this article. The published historical evidence on the transatlantic slave
      trade and New World slavery (from the 16th century to the 19th century) reveals
      that conditions existed for "natural selection," and therefore, genetic changes
      were virtually inevitable in the slave populations. During this period of
      history, mortality was extremely high, and fertility (or reproductive success)
      was so low among the survivors that most plantation societies in the western
      hemisphere depended on a constant importation of captives (over 12 million) from
      Africa for the viability of the plantation communities. Because the major causes
      of death were salt-depletive diseases such as diarrhea, fevers, and vomiting, it
      is argued that individuals with an enhanced genetic-based ability to conserve
      salt had a distinct survival advantage over others and were, therefore, more
      likely to bequeath their genotype to subsequent generations of Western hemisphere
      blacks. Thus, it is predicted that blacks in the Americas have a greater
      frequency of individuals with an enhanced genetic-based ability to conserve salt
      than African blacks.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1986990
TI  - An evolutionary perspective on salt, hypertension, and human genetic variability.
AB  - Natural selection for electrolyte conservation has likely been the norm
      throughout human evolutionary history. However, the current patterns of excessive
      dietary salt intake create the potential for salt overload. Under these
      conditions, hypertension may be considered an expected pathological response to
      an evolutionarily new constraint. The transatlantic Middle Passage may have
      created a genetic bottleneck for salt conservation in African-Americans. Although
      the initial consequences of this important historical event probably constricted
      genetic variability and further magnified the potential for salt-sensitive
      hypertension, the Middle Passage undoubtedly also served as a more generalized
      major source of environmental stress and may have stimulated subsequent
      hereditary diversity in the survivors of this holocaust and their descendants.
      Accelerated rates of mutation, genetic recombination, and transposable genetic
      elements in conjunction with enhanced opportunities for gene flow, new selective
      pressures, and drift have all contributed to the tremendous heterogeneity of
      contemporary African-Americans. It is unlikely that a single genetic event, even
      of the severity of the Middle Passage, can account comprehensively for the
      apparent susceptibility of this macroethnic group to high blood pressure and
      hypertension.

PMID- 1986991
TI  - Role of salt in the control of blood pressure in obesity and diabetes mellitus.

PMID- 1986992
TI  - Clinical interaction of salt and weight change on blood pressure level.
AB  - Studies that examine the effect of altered body weight or dietary sodium on blood
      pressure level are reviewed. Emphasis is placed on studies that compare the
      effects of weight reduction or sodium restriction in separate comparison groups
      or analyze the independent effect of the two intervention modalities in multiple
      regression analysis. Additional analyses of the Hypertension Prevention Trial
      data are presented. Most studies, where comparison can be made, suggest a greater
      effect for weight reduction than for the achieved, moderate, or short-term
      reduction in sodium intake on subsequent lowering of blood pressure; the lowering
      effect on blood pressure of weight reduction is independent of the effect of
      dietary sodium restriction. However, long-term (over a year) substantial
      reductions (up to 70 meq/day) of dietary sodium have not been achieved in
      comparative trials, nor are the effects of combined weight and sodium reduction
      in the prevention and treatment of hypertension quantified. Future studies and
      potential problems are discussed.

PMID- 1986993
TI  - Interactions among calcium, sodium, and alcohol intake as determinants of blood
      pressure.
AB  - It has been reported that calcium intake may effectively modulate the expression
      of hypertension affected by sodium. The present study extends our previous
      analysis of this calcium-sodium interaction, additionally demonstrating that
      calcium, sodium, and alcohol intake further contribute to both systolic and
      diastolic blood pressures in normotensive subjects. Calcium intake was related to
      lower blood pressure over all ranges of sodium and alcohol intake, and alcohol
      intake contributed positively and significantly to both systolic and diastolic
      blood pressures. However, sodium was associated with increased blood pressure
      only at low calcium intake, particularly in subjects who consumed large amounts
      of alcohol. This study points to a significant interaction among sodium, calcium,
      and alcohol intake as determinants of blood pressure, which, together with gender
      and weight, contribute to 31% of systolic blood pressure and with the addition of
      age to 36% of the variance in diastolic blood pressure.

PMID- 1986994
TI  - Sodium-potassium interaction in hypertension and hypertensive cardiovascular
      disease.
AB  - Epidemiological evidence suggests that low potassium intake is associated with
      the probability of occurrence of hypertension and stroke. The short-term response
      to increased potassium intake is increased sodium excretion as well as increased
      potassium excretion; the short-term response to increased sodium intake is
      increased potassium excretion as well as increased sodium excretion. In some
      experimental studies, increased amounts of potassium have been able to block the
      noxious influences of sodium. Sodium and potassium must be concomitantly
      considered in the investigation of the association of either of these cations
      with hypertension and cardiovascular disease. The chloride ion is also important
      for sodium's effects; its importance in potassium's effects has not been
      extensively explored.

PMID- 1986995
TI  - Importance of dietary chloride for salt sensitivity of blood pressure.
AB  - Recent evidence indicates that the anion accompanying sodium plays an important
      role in determining the magnitude of the blood pressure increase in response to a
      high dietary intake of NaCl. The purpose of this review is to describe studies of
      blood pressure responses to selective dietary sodium loading (without chloride)
      and to selective dietary chloride loading (without sodium) in several
      experimental models of salt-sensitive hypertension and in hypertensive humans.
      The full expression of salt sensitivity depends on high dietary intakes of both
      sodium and chloride. This observation has implications for understanding
      mechanisms contributing to NaCl-induced hypertension.

PMID- 1986996
TI  - Implications of the INTERSALT study.

PMID- 1986997
TI  - Interaction of sodium sensitivity and stress in young adults.
AB  - The interaction of sodium sensitivity and stress-induced cardiovascular
      reactivity was studied in white and black young adults aged 18-23 years. The
      cardiovascular response to difficult mental arithmetic was measured before and
      after 14 days of oral sodium loading (10 g NaCl/day added to the usual diet). A
      sodium-sensitive blood pressure response occurred in 18.4% of whites and 37.3% of
      blacks. A significant correlation between blood pressure change and sodium
      excretion occurred in the sodium-sensitive group (r = - 0.28, p less than 0.01).
      High sodium intake did not augment blood pressure or heart rate response to the
      beta-adrenergic-mediated stimulus of mental arithmetic in the population, which
      was grouped by blood pressure, race, or sodium sensitivity.

PMID- 1986998
TI  - A perspective on the salt-blood pressure relation.
AB  - Current recommendations for a population-wide decrease in dietary salt
      consumption come from a conclusion that a substantial portion of the population
      with essential hypertension is salt-sensitive. It is difficult to determine the
      appropriateness of these recommendations because of critical gaps in knowledge of
      the salt-blood pressure relation. There is no agreement on a definition of salt
      sensitive blood pressure changes. There is no consensus about mechanisms of
      changes; several have been suggested but none seems universal. In fact, differing
      results suggest marked heterogeneity in the mechanisms of salt-sensitive
      hypertension, and some evidence points to the possibility that arterial pressure
      of hypertensive subjects is controlled differently than that of normotensive
      subjects during manipulation of salt intake. Because salt-sensitive blood
      pressure changes are not always related to the magnitude of the positive sodium
      balance, it seems possible that for some people the current recommendations for
      modest dietary sodium restriction may be inadequate to influence blood pressure
      control for the prevention of hypertension.

PMID- 1986999
TI  - A consensus approach to electrolytes and blood pressure. Could we all be right?
AB  - This commentary sets forth the hypothesis that the putative beneficial or
      detrimental effects of specific electrolytes on blood pressure regulation in fact
      reflect highly integrated responses to interactions among these cationic and
      anionic species. In this paradigm, the impact of any given intake of an
      electrolyte on arterial pressure will be influenced by the concurrent consumption
      of other electrolytes. Thus, the heterogeneous blood pressure response in humans
      to isolated manipulations of nutrients such as sodium, calcium, and potassium may
      be determined, in part, by the adequacy of the dietary intake of other mineral
      elements. If this hypothesis is validated by continued research in this area, we
      would have new strategies available to improve blood pressure control in humans.
      For example, treatment of "NaCl sensitivity" in some humans might be more
      effectively approached by correcting dietary deficiencies of either potassium or
      calcium than by restricting dietary NaCl.

PMID- 1987000
TI  - High salt intake. Sensory and behavioral factors.
AB  - Salt (NaCl) is a ubiquitous component of diets in developed countries. A major
      reason for this is that people judge many salted foods as more palatable than the
      same foods without salt. Because recent evidence indicates that an acceptable
      salt substitute is unlikely, an understanding of the behavioral and sensory
      factors involved in maintaining high salt preference is a prerequisite to
      successful programs aimed at reducing intake. Although little evidence exists for
      a genetic determination of individual differences in consumption and preferred
      level of salt, more research in this area is necessary. Considerable data support
      the view that the optimal level of salt in the diet is determined in part by the
      level an individual is currently consuming; increasing or decreasing customary
      salt intake, as long as the salt is tasted, increases or decreases the preferred
      level of salt in food. Although these data are consistent with a hypothesis that
      optimal salt preferences are learned, other data, from both animal models and
      human developmental studies, suggest that salt preference has an innate
      component. Furthermore, early experience with low or high salt diets may have a
      long-term impact on preferred salt levels. Liking for salt, similar to liking for
      sweets, has an innate basis that can be modified by individual experience.

PMID- 1987001
TI  - Dietary sodium reduction for hypertension prevention and treatment.
AB  - Nutritional-nonpharmacological approaches for the treatment and prevention of
      hypertension are of great interest. Sodium reduction is one of the primary
      methods recommended for these purposes. The general public is interested in the
      reduction of dietary sodium intake and has responded with a decrease in table
      salt use, the purchase of lowered sodium food products, and the use of food
      labels to help guide food purchases. Countervailing trends in the use of
      convenience foods and dining out increase the difficulty for individuals to lower
      sodium intake. Clinical trials that have used sodium reduction alone or in
      combination with other lifestyle therapies have demonstrated the feasibility of
      reducing dietary sodium intake from 30% to 50% for up to 4 years, in a variety of
      populations. Trials that used lifestyle and weight loss interventions have also
      achieved significant reductions in body weight and alcohol consumption and
      increases in physical activity. A variety of studies indicate that long-term
      sodium reduction is feasible and that it is acceptable to patients. No negative
      consequences of these interventions have been observed, and in some cases
      improvement in the intake of other nutrients has occurred. Nonpharmacological
      interventions have resulted in hypertension control in significant proportions of
      the trial populations. These studies demonstrate that the foregoing types of
      interventions can significantly contribute to hypertension treatment and
      prevention.

PMID- 1987002
TI  - Behavioral aspects of intervention strategies to reduce dietary sodium.
AB  - This article addresses general and specific aspects of dietary sodium
      interventions from the perspective of behavioral change. Changing dietary
      behavior requires relearning a range of habitual behaviors involved in day-to-day
      eating situations in the context of a diverse and complex food supply and in
      consideration of numerous factors, other than health concerns, that influence
      habitual eating patterns. Potential obstacles to dietary sodium reduction relate
      to the wide distribution of sodium in foods, the strong cultural values for salt,
      and the difficulty of assessing success in sodium reduction. A review of sodium
      interventions reported in the literature suggests that state-of-the-art
      behavioral change strategies can be effective in achieving reductions in sodium
      intake to around 3,000 mg/day but that this level is achieved only with highly
      motivated individuals and when a high level of intervention (i.e., intensive and
      multifaceted) is provided. Thus, in regard to sodium reduction in the general
      population, either the goal will have to be modest or the food supply will have
      to change so that substantial decreases in sodium intake can be accomplished with
      less intensive and less costly interventions.

PMID- 1987003
TI  - Health promotion roles of the federal government and food industry in nutrition
      and blood pressure.
AB  - Some principal activities of government that pertain to nutrition and blood
      pressure are education, information, dietary guidance, food regulatory practices,
      health and nutrition monitoring, biomedical research and training, and
      legislation. The food industry, in turn, influences the marketplace and food
      consumption by its response to government activities and policies. Dietary
      guidance recommendations call for moderation of dietary intake, improved
      nutrition, and greater availability in food choices in the marketplace that are
      consistent with dietary recommendations to reduce chronic disease risk. Health
      and nutrition monitoring allows measurement of the effectiveness of moderating
      dietary intake and controlling hypertension. Adequate support of education,
      nutrition and health monitoring, and biomedical research and training is
      necessary to control and prevent hypertension. Cooperation between government and
      industry can contribute to the decline in cardiovascular disease, which in 1987
      cost this nation in excess of $135 billion.

PMID- 1987004
TI  - A perspective on reducing salt intake.
AB  - Epidemiological, clinical, and experimental evidence links excessive salt
      consumption to hypertension; there appears to be no evidence that it is
      beneficial. I conclude that it should be public policy to advise and help
      Americans to reduce their salt intake. Because even mild hypertension increases
      risk, the overall problem does not appear to be amenable to treatment, although
      treatment for those with clinical hypertension will always be needed. There
      appears to be little likelihood that identification of those "at risk" will be
      successful, nor does it appear that we have the capacity at this time to conduct
      successful preventive field trials. It is difficult for the individual to modify
      his diet alone. The successful strategy is to modify the food supply by changing
      public demand. The public responds to dietary advice if acceptable and
      identifiable products are available. Because most of the salt is in commercially
      prepared foods and because their consumption will increase in the future, the
      major responsibility for lowering salt consumption will fall on the food
      manufacturers. They are beginning to respond, and there appears to be ample
      opportunity for them to reduce the salt content of foods markedly. Our temporary
      objectives, however, should be modest, because unrealistic objectives only
      discourage those who attempt to follow them.

PMID- 1987006
TI  - Sodium chloride raises blood pressure in normotensive subjects. The study of
      sodium and blood pressure.
AB  - The effects of dietary sodium on blood pressure in normotensive adults is not
      well characterized. The Study of Sodium and Blood Pressure (SNaP) is a
      randomized, double-blind crossover trial using a placebo or 96 meq sodium in 4
      week treatment periods separated by a 2-week washout period. Before capsule
      treatment periods, participants were instructed in a low sodium diet for 10 weeks
      to reduce urinary sodium excretion to less than 35 meq/8 hr. The low sodium diet
      was continued throughout the capsule treatment periods. Participants (n = 48; 47
      white, 1 black) were 79% male and had an average age of 52 years, a body mass
      index of 27.6, and a baseline blood pressure of 131/84 mm Hg. Baseline overnight
      urinary sodium excretion was 51 meq/8 hr and 19 meq/8 hr after the low sodium
      diet run-in period, before the capsule treatment periods began. Resting, seated
      blood pressure was measured twice at each visit in a standard fashion.
      Differences between sodium and placebo treatment periods were as follows:
      systolic blood pressure, 123.9 versus 120.3 mm Hg, respectively (p less than
      0.001); diastolic blood pressure, 78.7 versus 76.4 mm Hg, respectively (p =
      0.005); and sodium excretion, 51.3 versus 30.9 meq/8 hr, respectively (p less
      than 0.001). Both systolic and diastolic blood pressures increased significant
      amounts in normotensive adults on a low sodium diet supplemented with 96 meq/day
      sodium. Long-term effects and dose-response relations need further study.

PMID- 1987005
TI  - Salt and hypertension--future directions.
AB  - The comments that follow reflect the personal views of this author regarding some
      useful directions of research in the field of salt and hypertension. From a
      physiological perspective, salt sensitivity is defined, and the merits and
      limitations of certain animal models of hypertension used to study this issue are
      discussed. The need to more clearly define the mechanisms that detect sodium
      intake and control the renal excretion of sodium is discussed. Additionally, the
      need to better understand the relation between sodium homeostasis, volume
      regulation, and the consequences of dysfunction in these regulatory system on the
      arterial vasculature and interstitial matrix is emphasized. The necessity for the
      application of new tools and approaches in a number of investigative areas is
      discussed. Finally, the necessity of equally imaginative whole animal and
      cell/molecular research and efforts to merge and integrate the data obtained at
      the cellular level with that of intact systems is emphasized.

PMID- 1987007
TI  - Research and policy directions. Salt and blood pressure.
AB  - The relation between dietary intake of sodium chloride and blood pressure levels
      remains controversial. The critical questions concern whether there is a
      susceptible subgroup at risk of elevated blood pressure because of sodium
      chloride consumption. If there is such a subgroup, what is its size and how can
      it be identified? Further clinical trials are needed to determine the long-term
      effects of sodium chloride reduction on blood pressure. The risk of disease,
      including stroke and coronary heart disease, is linear with blood pressure
      levels. A small change in blood pressure can have a relatively large impact on
      disease, even within the normal range of blood pressure.

PMID- 1987008
TI  - An overview of randomized trials of sodium reduction and blood pressure.
AB  - To test for effects on systolic and diastolic blood pressure and to provide
      precise estimates of their magnitude, we conducted an overview of randomized
      clinical trials that aimed to reduce the intake of sodium in human subjects. We
      excluded from pooled analyses trials with confounded designs, those that compared
      intake levels beyond the usual range in the population, and those without
      published reports. Two reviewers abstracted information in duplicate and
      differences were reconciled. Twenty-three trials with outcome data from an
      aggregate of 1,536 subjects were included. Data were pooled both separately for
      hypertensive and normotensive subjects and for all trials combined. With the use
      of sample size weighting, blood pressure reductions (net of controls) were 4.9 +/
      1.3/2.6 +/- 0.8 mm Hg (systolic and diastolic, respectively, with 95% confidence
      limits) in hypertensive subjects and 1.7 +/- 1.0/1.0 +/- 0.7 mm Hg in
      normotensive subjects. The combined blood pressure reductions were 2.9 +/-
      0.8/1.6 +/- 0.5 mm Hg. These changes were associated with mean reduction of
      urinary sodium excretion ranging from 16 to 171 mmol/24 hr for individual trials.
      A dose-response relation across trials was found, both in normotensive and in
      hypertensive subjects. These results indicate that sodium reduction lowers mean
      blood pressure in both hypertensive and normotensive individuals for periods of
      at least several months. The findings are highly consistent with results of
      observational epidemiological studies and have implications for preventive
      strategies of blood pressure control.

PMID- 1987010
TI  - Commentary on epidemiological studies and intervention trials.

PMID- 1987009
TI  - Observational studies of salt and blood pressure.
AB  - The observational data relating salt and blood pressure (excluding INTERSALT) are
      reviewed. Important methodological difficulties and biases are inherent to both
      across- and within-population studies and confuse their interpretation. Across
      population studies are positive but rely on data drawn from the international
      literature based on a variety of unstandardized field methods; they are prone to
      unmeasured (ecological) confounding. Within-population studies generally lack
      statistical power and are subject to major regression-dilution bias (because of
      considerable day-to-day variation in sodium intake), which could conceal true
      correlations between sodium and blood pressure. Nevertheless, an overview of
      reported studies that used 24-hour urine excretion to quantify intake shows
      positive and highly significant correlations between sodium and blood pressure
      for both men and women and for systolic and diastolic blood pressures. These
      results are consistent with the INTERSALT findings and those from trials of
      sodium restriction.

PMID- 1987011
TI  - Neurovascular mechanisms and sodium balance in the pathogenesis of hypertension.
AB  - Physiological studies have clarified the role that the brain has in the interplay
      between salt balance and hypertension. Neural mechanisms and endocrine secretions
      play a pivotal role in the adaptation of mammals to changes in the intake and
      excretion of sodium. Maneuvers that alter the concentration of sodium in the
      plasma modify the sensitivity of baroreceptor reflexes and alter vascular
      reactivity. These changes may be mediated in part by the release of vasopressin.
      The research also suggests that the brain indirectly modulates the ability of the
      vascular endothelium to release vasoactive factors. Collectively, these studies
      illustrate the multiple effects of the sodium ion on the peripheral neural and
      central endocrine mechanisms that participate in the regulation of arterial
      pressure.

PMID- 1987012
TI  - Salt and hypertension. Lessons from animal models that relate to human
      hypertension.
AB  - A high NaCl diet can raise blood pressure in both susceptible people and in
      susceptible animals, and the mechanisms are probably quite similar for both
      humans and animals. The possibly harmful effects of a high NaCl diet are not
      unexpected since both prehistoric man and mammals evolved in a low NaCl world.
      Evolutionary forces molded mammals to adapt well to a low sodium intake; the
      modern high NaCl intake goes "against the grain" of this adaptation. The high
      NaCl diet can cause premature mortality by raising blood pressure in susceptible
      people. We have new evidence that in a hypertensive setting, a high NaCl diet can
      increase mortality even though it does not cause a further rise of blood
      pressure. Multiple small cerebral infarcts are a partial cause of this excess
      mortality. Recent evidence also indicates that a high potassium diet reduces the
      rise of blood pressure caused by a high NaCl diet, whereas a low normal potassium
      intake encourages an NaCl-induced rise of blood pressure. It is the combination
      of kidneys that tends to retain NaCl together with a high NaCl intake that
      produces a rise in blood pressure. This combination tends to cause NaCl
      retention, which can trigger a rise in blood pressure in susceptible humans and
      animals. Such a rise in blood pressure can augment renal NaCl excretion and
      regain the previous NaCl balance. In the Dahl salt-sensitive (DS) rat, there are
      several renal abnormalities that would tend to encourage sodium retention. By
      analogy, renal "abnormalities" are probably present in people susceptible to
      hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1987013
TI  - Salt sensitivity. Definition, conception, methodology, and long-term issues.
AB  - Several laboratories have examined the relation between salt intake and blood
      pressure in both experimental animals and humans. The human studies have used
      widely varying methodologies and different criteria for sodium sensitivity.
      Nonetheless, these studies have produced convincing data that the blood pressure
      of some individuals is far more sensitive to the effects of sodium depletion or
      loading than that of others. Furthermore, a minority of the population appears to
      comprise acutely salt-sensitive individuals. Some studies have shown that sodium
      sensitive individuals share several characteristics. They include increased
      forearm vascular resistance, decreased venous compliance, suppressed plasma renin
      activity, and lower circulating aldosterone concentration. These findings have
      also been described in the Dahl salt-sensitive rat, which suggest a genetic link
      in humans as well as the rat. Long-term follow-up of sodium-sensitive and sodium
      resistant groups has shown that although blood pressure levels are approximately
      equal in the two groups during sodium depletion, resumption of a daily sodium
      intake of about 150 meq results in significantly higher levels of blood pressure
      and forearm vascular resistance in the sodium-sensitive group. This difference
      persists for at least 12 months.

PMID- 1987014
TI  - Genetic traits related to hypertension and electrolyte metabolism.
AB  - The genetic and cultural heritability and intercorrelation of traits related to
      hypertension have been carried out in 98 Utah pedigrees (2,500 person) and 58
      sibships with two or more hypertensive persons (131 hypertensive persons).
      Although none of these traits has been established as a marker for "sodium
      sensitive hypertension," many of them are related at least indirectly to both
      electrolyte metabolism and risk of hypertension. Significant recessive monogenic
      effects and high total heritability (52-84%) were found for urinary kallikrein,
      high fat pattern index, intraerythrocytic sodium, Na-Li countertransport, and
      ouabain binding sites. Familial correlations more strongly attributable to shared
      environment than to genetic effects were found for Na,K-ATPase pump activity,
      intraerythrocytic magnesium, plasma digoxin-like factor, plasma renin activity,
      and plasma sodium concentration. All anthropometric variables tested showed
      highly significant genetic heritability with low and insignificant shared family
      environmental effects. Several of the genetically determined cellular cation
      tests also correlated with other genetic traits including plasma lipids,
      anthropometric measurements, and other cellular cation tests. Among hypertensive
      individuals with familial dyslipidemic hypertension, plasma insulin levels
      correlated with obesity and lipid abnormalities and with several cellular cation
      flux tests associated with hypertension.

PMID- 1987015
TI  - Membrane sodium transport and salt sensitivity of blood pressure.

PMID- 1987016
TI  - Non-modulating hypertension. A subset of sodium-sensitive hypertension.

PMID- 1987017
TI  - Sympathetic neural contribution to salt-induced hypertension in Dahl rats.
AB  - The Dahl strain provides a model for examining mechanisms involved in the genetic
      sensitivity or resistance to salt-induced hypertension. Dahl salt-sensitive rats
      develop hypertension when fed a high salt diet; Dahl salt-resistant rats remain
      normotensive. Based on early experiments, it was thought that hypertension in
      Dahl salt-sensitive rats epitomized the overriding importance of renal and
      humoral mechanisms in salt-induced hypertension, but studies in the past 15 years
      have demonstrated that alterations in sympathetic neural mechanisms also
      participate critically in the genetic predisposition to salt-induced hypertension
      in Dahl salt-sensitive rats. This article briefly reviews sympathetic neural
      mechanisms in Dahl rats, including evidence for a role of afferent baroreceptor
      as well as central neural and peripheral adrenergic mechanisms in salt-induced
      hypertension in Dahl salt-sensitive rats.

PMID- 1987018
TI  - Findings of the International Cooperative INTERSALT Study.
AB  - INTERSALT, an international cooperative study on electrolytes and other factors
      related to blood pressure, found, in within-population analyses involving 10,079
      persons, a significant positive association between 24-hour urinary sodium
      excretion and systolic blood pressure and between the sodium/potassium ratio and
      systolic blood pressure. These significant findings were derived from analyses
      for individuals from all 52 centers and from the 48 centers remaining when
      persons from four low sodium centers were excluded. Potassium excretion of
      individuals was significantly and independently related inversely to their
      systolic blood pressure. For men and women, both separate and combined, the
      relation between sodium and systolic blood pressure was stronger for older than
      younger adults, perhaps reflecting the result of longer exposure with age or
      diminished capacity to handle a sodium load. Relations between electrolyte
      excretion and diastolic blood pressure in individuals were weaker than for
      systolic blood pressure. Body mass index and heavy alcohol consumption of
      individuals were strongly and independently related to blood pressure. In cross
      population analyses with n = 52 or n = 48, sample median sodium excretion was
      significantly and independently related to the slope of systolic blood pressure
      and diastolic blood pressure with age. Other ecological analyses yielded
      inconsistent results. Four isolated populations showed low sodium excretion, low
      sodium/potassium excretion, low body mass index, and low alcohol consumption;
      sample median blood pressures were low, there was little or no upward slope of
      blood pressure with age, and high blood pressure was rare or nonexistent.

PMID- 1987019
TI  - Relation between sodium intake, renal function, and the regulation of arterial
      pressure.
AB  - The long-term regulation of arterial pressure requires the maintenance of a
      balance between sodium and water intake and sodium and water excretion. Normal
      salt and water balance leads to stable body fluid volumes and the maintenance of
      normal renal function is critical to establishing extracellular fluid volume
      homeostasis. This review focuses on the role of the kidney in the long-term
      control of salt and water balance with particular emphasis on the relations
      between sodium intake, the renin-angiotensin-aldosterone system, renal
      sympathetic nerve activity, and the regulation of arterial pressure via renal
      sodium and water excretion. The accumulation of evidence in recent years
      demonstrates that low level elevation of renin release, circulating angiotensin
      II or aldosterone, or activation of renal sympathetic outflow may alter renal
      function such that normal natriuretic and diuretic responses to arterial pressure
      are significantly impeded. Under these circumstances, the maintenance of normal
      sodium and water excretion requires a significant elevation of arterial pressure.
      Thus, compromised renal function leads to elevation of arterial pressure to
      maintain adequate sodium and water balance during periods of increased sodium
      intake. The resultant chronic elevation of arterial pressure then becomes a
      compromise that is used by the kidneys to maintain normal extracellular body
      fluid volumes.

PMID- 1987020
TI  - Dietary salt and blood pressure. A perspective.
AB  - Although dietary salt restriction is often valuable as sole or adjunctive therapy
      of hypertensive disorders, it is abundantly clear that hypertensive patients
      comprise a heterogeneous group with regard to salt sensitivity of blood pressure.
      This is apparent despite the many methodological obstacles to defining salt
      sensitivity in an individual patient. Currently, dietary trial is the only sure
      means of defining a given patient as responsive to salt restriction. Easily
      definable markers of salt sensitivity would allow appropriate targeting of this
      rather ponderous therapy. Promising leads include the assessment of membrane ion
      transporters such as sodium-lithium exchange and of the activity of the renin
      angiotensin system, including the phenomenon of "non-modulating" hypertension and
      other volume regulatory hormones such as atrial natriuretic factor. Although less
      intensively studied than in hypertensive patients, the blood pressure response of
      normal subjects to salt restriction is also marked by great variability. Given
      the possibility of deleterious consequences of population-wide salt restriction
      for at least some people in a setting such as the United States, it seems
      imprudent to recommend such a policy before its proven worth has been
      demonstrated by clinical trial. Pending such evidence and the development of
      markers, salt restriction should be reserved for those in whom it is of
      demonstrated efficacy.

PMID- 1987021
TI  - Adherence of Porphyromonas (Bacteroides) gingivalis to Streptococcus sanguis in
      vitro.
AB  - Intergeneric bacterial adherence is responsible for the complexity of the
      microbiota in human dental plaque and is believed to enable some extraneous
      bacteria to initially colonize the human oral cavity. Some current evidence
      indicates that Streptococcus sanguis, an early colonizer of teeth, enhances
      subsequent colonization by Porphyromonas (Bacteroides) gingivalis, a bacterium
      associated with advanced adult periodontitis. In this study, selected strains of
      P. gingivalis and S. sanguis were tested for their adherence activities in vitro.
      A differential filtration assay was devised in which one member of the test pair
      was radiolabeled. Heterogeneous aggregates that formed in mixed suspensions were
      collected on polycarbonate filters (8-microns pore size) and were washed free of
      individual bacteria and small homologous clumps. P. gingivalis 381, W50, JKG7,
      and 33277 adhered to S. sanguis G9B, M5, Challis 6, and 38. P. gingivalis A7A1-28
      did not adhere well to S. sanguis under these conditions. More precise
      measurements of intergeneric adherence were obtained with an alternative assay
      with radiolabeled P. gingivalis and an artificial dental plaque composed of S.
      sanguis coupled to cyanogen bromide-activated agarose beads. CNBr-agarose was
      selected as the supporting matrix for the plaque because it was uniformly and
      permanently coated with S. sanguis and because P. gingivalis had negligible
      adherence activity for streptococcus-free beads. P. gingivalis W50 grown to the
      early stationary phase adhered to S. sanguis-coated beads in higher numbers than
      either midlogarithmic- or late-stationary-phase cells. Intergeneric adherence was
      not inhibited or reversed by the presence of lactose or other monosaccharides or
      disaccharides. Pretreatment of either bacterium with trypsin or proteinase K
      reduced subsequent adherence by 86 to 100%. Neuraminidase treatment of P.
      gingivalis caused 98% reduction of adherence, whereas similar treatment of S.
      sanguis caused only a 2% loss. Preincubation of P. gingivalis at 60 degrees C for
      30 min decreased subsequent adherence to S. sanguis-coated beads by 94%.
      Adherence was reduced by 96% when bacteria were assayed while suspended in human
      whole saliva or when pretreated with saliva and subsequently assayed in buffer.
      The concentration of whole human saliva required to inhibit 50% adherence in this
      assay was 23 micrograms per ml (1:200 dilution). Suspension of the bacteria in
      normal rabbit serum resulted in 94% inhibition of adherence. These data indicate
      that saliva and serum may be important host defense factors for controlling
      Porphyromonas-Streptococcus adherence.

PMID- 1987022
TI  - Resistance of Escherichia coli to osmotically introduced complement component C9.
AB  - Investigation into the action of osmotically introduced C9 in Escherichia coli
      (in the absence of any other complement components) revealed that C9 could
      inhibit inner membrane respiration and cause a decrease in the viability of cells
      that were normally complement sensitive. This effect is analogous to the loss of
      inner membrane function and viability due to the assembly of the C5b-9 complex on
      these cells. Complement-resistant cells showed no such inhibition of respiration
      or loss of viability when subjected to the osmotic introduction of C9. The reason
      for this failure of C9 to affect complement-resistant cells was explored to
      determine whether this resistance to C9 was due to an inability of proteins in
      general to be osmotically introduced into the complement-resistant cells. The
      protein toxins melittin and colicin E1 were showed to be able to kill these
      complement-resistant cells (as well as complement-sensitive cells) when
      osmotically introduced into the periplasm. Therefore, cellular resistance to
      osmotically introduced C9 is not due to an inability of proteins to be introduced
      into the cells and may be related to a mechanism of cellular resistance to the
      C5b-9 complex.

PMID- 1987023
TI  - Protein D, an immunoglobulin D-binding protein of Haemophilus influenzae:
      cloning, nucleotide sequence, and expression in Escherichia coli.
AB  - The gene for protein D, a membrane-associated protein with specific affinity for
      human immunoglobulin D, was cloned from a nontypeable strain of Haemophilus
      influenzae. The gene was expressed in Escherichia coli from an endogenous
      promoter, and the gene product has an apparent molecular weight equal to that of
      H. influenzae protein D (42,000). The complete nucleotide sequence of the gene
      for protein D was determined, and the deduced amino acid sequence of 364 residues
      includes a putative signal sequence of 18 amino acids containing a consensus
      sequence, Leu-Ala-Gly-Cys, for bacterial lipoproteins. The sequence of protein D
      shows no similarity to those of other immunoglobulin-binding proteins. Protein D
      is the first example of immunoglobulin receptors from gram-negative bacteria that
      has been cloned and sequenced.

PMID- 1987024
TI  - Beneficial effect of liposome-encapsulated muramyl tripeptide in experimental
      septicemia in a porcine model.
AB  - In a porcine model of pneumococcal septicemia, animals were pretreated with 1 mg
      of liposome-encapsulated muramyl tripeptide phosphatidylethanolamine (MTP-PE) or
      with liposomes alone. After 24 h each animal received an injection of either
      10(9) or 10(10) pneumococcal serotype 6B cells. MTP-PE pretreatment resulted in
      less pronounced leukocytopenia, with a nadir of 6,700 (versus 4,100) leukocytes
      per mm3 after injection of 10(9) bacteria and a nadir of 4,400 (versus 3,800)
      leukocytes per mm3 after injection of 10(10) bacteria. At the same time bacterial
      clearance was substantially improved by MTP-PE pretreatment. Finally,
      pretreatment with MTP-PE dramatically reduced mortality; the average death rates
      for both series of animals used were 55% for liposome-pretreated animals and 3%
      for animals pretreated with MTP-PE-containing liposomes. These results in a
      preclinical model suggest that treatment with MTP-PE-containing liposomes might
      be beneficial in controlling septicemia in patients at risk.

PMID- 1987025
TI  - An upstream regulatory sequence stimulates expression of the perfringolysin O
      gene of Clostridium perfringens.
AB  - The structural gene for perfringolysin O (pfoA), a thiol-activated hemolysin of
      Clostridium perfringens, was cloned into Escherichia coli JM109 on a 4.6-kilobase
      (kb) EcoRI-NdeI fragment which contained the 1.7-kb pfoA gene and an upstream 2.9
      kb region. An E. coli strain transformed by this plasmid produced 20-fold more
      perfringolysin O than a strain containing only the 1.7-kb pfoA gene. The
      stimulatory effect of the upstream region on in vivo expression of the pfoA gene
      was further analyzed by using a set of deletion mutants. Stimulation was still
      observed with a 3.9-kb fragment, but stimulation was not observed with fragments
      that were 3.6 kb or less long, indicating that the upstream region between 3.9
      and 1.7 kb was involved in activation of pfoA gene expression. Nucleotide
      sequencing showed that this region contained one open reading frame (pfoR) coding
      for 343 amino acids. The deduced amino acid sequence of pfoR possesses several
      motifs that are characteristic of DNA-binding proteins. When a region coding for
      a helix-turn-helix, one of the most important motifs of DNA-binding proteins, was
      deleted within pfoR, stimulation was completely abolished. These results indicate
      that pfoR positively controls expression of the pfoA gene.

PMID- 1987026
TI  - Prostaglandins in experimental syphilis: treponemes stimulate adherent spleen
      cells to secrete prostaglandin E2, and indomethacin upregulates immune functions.
AB  - Incubation of microorganisms with macrophages enhances the production of
      prostaglandin E2 (PGE2). Previous research had indicated that macrophages from
      syphilitic rabbits suppressed spleen cell synthesis of interleukin-2 (IL-2); this
      suppressive activity was reversed by indomethacin. Experiments were designed to
      further characterize the involvement of prostaglandins in immune processing. When
      Treponema pallidum was incubated with unfractionated spleen preparations, PGE2
      production was accelerated, and within 24 h, pharmacologic concentrations of the
      prostaglandin were detected. When cytochalasin B was used to block phagocytosis,
      decreased levels of PGE2 were apparent. Commercial preparations of PGE2, in the
      range generated by macrophage-treponeme interaction, inhibited concanavalin A
      induced IL-2 secretion by splenic cells. T. pallidum stimulated IL-1 production
      by adherent cells, and indomethacin markedly enhanced this effect. In vivo,
      indomethacin upregulated immune function. Two groups of rabbits were infected,
      and one was given daily injections of indomethacin for 18 days. Both groups were
      treated with penicillin to terminate infections. One week later, rabbits were
      challenged with viable organisms to determine their immune status. The
      indomethacin-treated group was more resistant to reinfection. In further
      research, indomethacin enhanced the immunogenicity of vaccine preparations
      containing heat-killed T. pallidum. Results are discussed in terms of the role of
      PGE2 as it impinges on immune functions involving macrophage activation (IL-1
      production) and T lymphocyte activation (IL-2 production).

PMID- 1987027
TI  - Construction and expression of the complete Clostridium difficile toxin A gene in
      Escherichia coli.
AB  - Cloned fragments constituting the 8.1-kb toxin A gene of Clostridium difficile
      were used to reconstruct the intact gene. The recombinant toxin expressed in
      Escherichia coli was cytotoxic, enterotoxic, and lethal. In addition, toxic
      lysate caused hemagglutination of rabbit erythrocytes. The toxic activities were
      inhibited by antibody specific for toxin A. Our findings demonstrate that the
      biological activities exhibited by native toxin A are functions of a single
      protein encoded by the 8.1-kb toxin A gene, independent of any other C. difficile
      gene products.

PMID- 1987028
TI  - Penetration and replication of Edwardsiella spp. in HEp-2 cells.
AB  - The ability of 22 Edwardsiella strains to penetrate and replicate in cultured
      epithelial cells was initially evaluated by light microscopy methods and by the
      recovery of gentamicin-resistant (Gmr) bacteria from the Triton X-100 cell
      lysates of HEp-2-infected monolayers. Giemsa-stained HEp-2 cells revealed the
      presence of numerous internalized bacteria 3 h postinfection, often appearing as
      parallel rows of replicated bacteria within the cytosol and sometimes
      obliterating the cytoplasm because of the large numbers of bacilli present.
      Invasive bacteria were also sometimes found within cytoplasmic vacuoles in
      infected cells; thin-section electron micrographs of HEp-2-infected cells
      supported these conclusions. Results of light microscopy studies and cell lysate
      assays indicated that most Edwardsiella tarda (92%) and some Edwardsiella
      hoshinae strains were invasion positive on one or more occasions, while
      Edwardsiella ictaluri isolates were uniformly negative. HEp-2 invasion by E.
      tarda was a microfilament-dependent (cytochalasin B- and D-sensitive) process,
      with maximum numbers of Gmr CFU recorded between 3 and 6 h postinfection. The
      small percentage (0.01 to 1.0%) of the challenge inoculum recoverable as Gmr
      progeny 3 to 6 h postinfection was attributed to a strong cell-associated (not
      filterable) hemolysin that was produced by a majority (85%) of the E. tarda
      strains but not by E. ictaluri and only minimally by E. hoshinae. This
      cytolysin/hemolysin was responsible for the toxic effects observed in HEp-2 cells
      during the infection-replication process of edwardsiellae and appears to play a
      role in the release of internalized and replicated bacteria from infected cells.
      The results suggest an invasion strategy with some similarities to and
      differences from those of other recognized enteroinvasive pathogens.

PMID- 1987029
TI  - Pathogenicity of Yersinia kristensenii for mice.
AB  - Forty-seven strains of Yersinia kristensenii from widely differing sources,
      representing all known O serogroups of this species, were investigated for
      virulence with a variety of animal and in vitro assays. Twenty-four (51%) of the
      isolates were lethal for mice pretreated with iron dextran. Mouse-lethal strains
      occurred predominantly within O serogroups O:11, O:12,25, and O:16. Virulent Y.
      kristensenii strains generally did not express the virulence-associated phenotype
      (Ca2+ dependence and binding of Congo red and crystal violet) which characterizes
      virulent strains of Y. enterocolitica, nor did they carry the Yersinia virulence
      plasmid. Although all strains hybridized with a DNA probe derived from the inv
      (invasin) gene of Y. enterocolitica, none was able to invade HEp-2 epithelial
      cell culture. Y. kristensenii strains were virulent only when inoculated
      parenterally into iron-loaded mice. Animals infected in this way succumbed
      rapidly to infection, generally within 24 h. This finding suggested that the
      pathogenicity of these bacteria may be attributable to a secreted toxin, but a
      search for such a substance and for other in vitro correlates of pathogenicity
      was unsuccessful. These observations indicate that some strains of Y.
      kristensenii kill mice by a mechanism not previously recognized in yersiniae.

PMID- 1987030
TI  - Heat-labile enterotoxin can be released from Escherichia coli cells by host
      intestinal factors.
AB  - The heat-labile enterotoxin (LT) of Escherichia coli is localized in the
      periplasm of the bacterial cell. Growth of an LT-producing strain of E. coli in
      the presence of bile salts, in concentrations within the range found in the human
      small intestine, caused leakage of LT into the culture medium. This leakage could
      be augmented by the presence in the medium of trypsin and by minimizing the
      concentration of free iron.

PMID- 1987031
TI  - A monoclonal antibody against a Pasteurella multocida outer membrane protein
      protects rabbits and mice against pasteurellosis.
AB  - Monoclonal antibodies (MAbs) directed against the 37.5-kDa outer membrane protein
      were produced by fusing myeloma cells with spleen cells obtained from mice
      immunized with a pathogenic strain of Pasteurella multocida isolated from a
      rabbit. Desirable MAbs were selected by enzyme-linked immunosorbent assay, whole
      cell radioimmunoprecipitation (WC-RIP), and Western blot (immunoblot) analysis.
      WC-RIP and Western blot analyses, using MAb 1608 adsorbed with intact P.
      multocida cells and the eluted MAb, demonstrated that the antigen recognized by
      this MAb is exposed on the cell surface, is antibody accessible, and has an
      estimated molecular mass of 37.5 kDa. Treatment of outer membrane vesicles of P.
      multocida with proteinase K totally abrogated the MAb 1608 activity, indicating
      that this MAb binds to a protein antigenic determinant. Furthermore, MAb 1608 was
      nonreactive to purified lipopolysaccharide in Western blot analysis. Passive
      transfer studies showed that nine rabbits inoculated intranasally with MAb 1608
      and homologously challenged intranasally had significantly reduced mortality,
      severity of pneumonia, prevalence of P. multocida colonization in nonrespiratory
      organs, and numbers of P. multocida in nasal cavities compared with the controls.
      Furthermore, the number of P. multocida in lungs was reduced 84,750-fold.
      Similarly, passive transfer experiments indicated that MAb 1608 protected mice
      against homologous and heterologous challenges with P. multocida strains bearing
      the antigenic determinant recognized by MAb 1608. However, no protection was
      afforded by MAb 1608 when mice were challenged with a P. multocida strain lacking
      the antigenic determinant recognized by MAb 1608. This study establishes that the
      37.5-kDa outer membrane protein is the target for a protective MAb.

PMID- 1987032
TI  - Murine macrophage interleukin-1 release by capsularlike serotype-specific
      polysaccharide antigens of Actinobacillus actinomycetemcomitans.
AB  - Serotype-specific polysaccharide antigens (SPAs) were extracted from whole cells
      of Actinobacillus actinomycetemcomitans ATCC 29523 (serotype a), Y4 (serotype b),
      and NCTC 9710 (serotype c) by autoclaving and purified by chromatography on DEAE
      Sephadex A-25 and Sephacryl S-300 columns. Y4 SPA induced interleukin-1 (IL-1)
      release by P388D1 murine macrophages. Polymyxin B had virtually no effect on the
      release of IL-1. Rabbit anti-murine IL-1 serum strongly suppressed the
      proliferation of C3H/HeJ mouse thymocytes induced with the culture supernatants
      of Y4 SPA-stimulated P388D1 cells and a submitogenic dose of concanavalin A. Gel
      filtration of the culture supernatants of Y4 SPA-stimulated macrophages on
      Sephacryl S-200 showed that an IL-1 peak at a point corresponding to
      approximately 16.5 kDa was eluted. The ability of SPAs from strains ATCC 29523
      and NCTC 9710 to induce the release of IL-1 was lower than that of Y4 SPA. The IL
      1-releasing ability of serotype a and c antigens was enhanced by deacetylation of
      both polysaccharides, suggesting that acetyl groups of these antigens might
      hinder the interaction between the antigens and macrophages.

PMID- 1987034
TI  - Frequency of the erythrogenic toxin B and C genes (speB and speC) among clinical
      isolates of group A streptococci.
AB  - DNA probes corresponding to the internal region of the erythrogenic toxin B and C
      genes, speB and speC, were used in hybridization studies with clinical isolates
      of Streptococcus pyogenes to determine the frequency of occurrence of these genes
      in a large population of group A streptococci. More than 500 strains from
      different geographical locations throughout the world were used in this study.
      The results from colony-lift hybridization experiments indicated that the
      frequency of occurrence of each toxin gene among all of these strains was 100%
      for speB and 50% for speC. Division of these strains into subgroups of general
      group A strains and strains associated with scarlet fever or rheumatic fever
      resulted in a frequency of occurrence of speC of about 50% for all subgroups. The
      speC gene was found to be more frequently associated with serotype M2, M4, and M6
      strains and less frequently associated with serotype M1, M3, and M49 strains. The
      results from a similar study with the speA gene have been previously reported (C.
      E. Yu and J.J. Ferretti, Infect. Immun. 57:3715-3719, 1989).

PMID- 1987033
TI  - Production and purification of heat-stable enterotoxin b from a porcine
      Escherichia coli strain.
AB  - Production of heat-stable enterotoxin b (STb) by porcine Escherichia coli strains
      belonging to serogroup O115 was evaluated in ligated intestinal segments of adult
      rats. The conditions for optimal production and detection of STb were studied by
      using the STb-producing strain 4247. As STb production was similar in complex
      Trypticase soy broth and minimal Davis medium, the latter was used for the
      fermentation of strain 4247 and the production of STb in large quantities. STb
      was then purified to apparent homogeneity by sequential ultrafiltration,
      ultracentrifugation, and preparative gel electrophoresis. The enterotoxin was
      purified more than 500-fold and exhibited a molecular weight of approximately
      5,000 as determined by urea-sodium dodecyl sulfate gel electrophoresis. Purified
      STb retained such chemical characteristics as resistance to heating (60 degrees
      C/30 min) and sensitivity to trypsin. A rabbit polyclonal antiserum was produced
      against the purified toxin. Numerous booster doses were required to obtain a
      significant enzyme-linked immunosorbent assay titer, suggesting that STb is a
      poor immunogen. Nevertheless, the antiserum was used successfully to discriminate
      between culture supernatants of STb-positive and STb-negative O115 E. coli
      strains, thus demonstrating the immunogenicity of purified STb.

PMID- 1987035
TI  - Cooperative complement- and bacterial lectin-initiated bactericidal activity of
      polymorphonuclear leukocytes.
AB  - The recognition of glycoconjugate receptors on sialidase-treated
      polymorphonuclear leukocytes (PMNs) by the Gal/GalNAc-reactive fimbrial lectin of
      Actinomyces viscosus T14V has previously been shown to initiate lactose
      inhibitable phagocytosis and subsequent killing of the bacteria. Although a
      mutant lacking fimbriae, A. viscosus 147, was not destroyed by this mechanism,
      the present studies demonstrate that the deposition of C3 fragments on this
      bacterium by anti-A. viscosus 147 immunoglobulin M (IgM) prior to incubation with
      either untreated or sialidase-treated PMNs correlated with a reduction in
      viability of approximately 2 log10. This bactericidal activity was unaffected by
      lactose. A similar decrease in viability was observed following the addition of
      untreated PMNs to A. viscosus T14V preincubated with anti-A. viscosus 147 IgM and
      complement, conditions favorable for C3- but not lectin-mediated bactericidal
      activity. Neither IgM nor complement alone was opsonic for either strain, and
      individually they did not alter killing of A. viscosus T14V by sialidase-treated
      PMNs or inhibition of this bactericidal activity by lactose. The number of viable
      A. viscosus T14V cells was decreased by approximately 3.5 log10 when the bacteria
      were incubated with IgM and complement prior to the addition of sialidase-treated
      PMNs, and lactose only partially inhibited this response. Thus, the PMN-dependent
      bactericidal activity initiated by the participation of both the actinomyces
      lectin and complement was significantly greater than that achieved by either
      ligand alone.

PMID- 1987036
TI  - PspA, a surface protein of Streptococcus pneumoniae, is capable of eliciting
      protection against pneumococci of more than one capsular type.
AB  - Monoclonal antibodies against pneumococcal surface protein A (PspA) have been
      shown to protect mice from fatal pneumococcal infection. PspA is highly variable
      serologically, raising the possibility that PspA from one strain might not be
      able to elicit protective responses against strains which possess serologically
      different PspA. We have prepared a lambda gt11 library of pneumococcal genomic
      DNA and identified a clone expressing PspA. The recombinant PspA in this phage
      lysate elicited protection against pneumococcal infections with three strains of
      two different capsular serotypes. This finding demonstrated that PspA could
      elicit a protective response in the absence of other pneumococcal antigens. The
      observed protection was probably antibody mediated because it could be passively
      transferred with immune sera. Lambda lysates producing pneumococcal proteins
      other than PspA failed to elicit protection against fatal pneumococcal infection.

PMID- 1987037
TI  - Asexual development of Cryptosporidium parvum within a differentiated human
      enterocyte cell line.
AB  - Unremitting diarrhea with malabsorption is associated with Cryptosporidium parvum
      infection of the small intestine in patients with AIDS. The lack of a well
      defined in vitro model of C. parvum infection has severely hampered research into
      the biology of cryptosporidial invasion of the host epithelial cell and
      development of new pharmacologic and immunologic therapies. The adherent human
      intestinal epithelial cell line HT29 when grown in glucose-free medium develops
      morphologic and functional characteristics of the small intestine enterocyte and
      was used to develop an in vitro model of infection. Cryptosporidium oocysts
      obtained from AIDS patients were applied to a monolayer of cloned, differentiated
      HT29.74 cells. Cells were fixed and stained to estimate the degree of parasite
      infection. Schizonts were easily distinguished from the host cell by light
      microscopy. Twenty-four hours after 10(5) oocysts were added to approximately
      10(6) HT29.74 cells, Cryptosporidium infection rates varied from 50 to 120
      schizonts per 1,000 cells. Among 14 different experiments, the mean infection
      rate was 91 (+/- 18) schizonts per 1,000 cells. Electron microscopy at 6 and 24 h
      confirmed intracellular localization and development of schizonts. The
      morphologic features of the cryptosporidial schizonts within HT29.74 cells, which
      included the presence of a dense band and feeder layer, were identical to those
      described during cryptosporidial infection of human enterocytes in patients with
      AIDS. Fewer schizonts were observed at 5 days and beyond. Infection of
      differentiated HT29.74 cells (62 and 65 schizonts per 1,000 cells at 24 and 72 h,
      respectively) was over five times more efficient than infection of
      undifferentiated HT29.74 cells (9 and 5 schizonts per 1,000 cells at 24 and 72 h,
      respectively). In vitro infection of differentiated HT29.74 cells will allow a
      better understanding of the mechanisms by which C. parvum infects the small
      intestinal epithelium and will allow a systematic evaluation of new therapeutic
      agents.

PMID- 1987038
TI  - Killing of Cryptococcus neoformans strains by human neutrophils and monocytes.
AB  - The susceptibility of various strains of Cryptococcus neoformans to killing by
      human polymorphonuclear leukocytes (PMNs) and monocytes was investigated. Five
      previously characterized strains of C. neoformans serotype A, a capsule-free
      mutant, and six recent clinical isolates were compared. PMNs and monocytes were
      isolated from normal peripheral blood and allowed to adhere to the flat-bottom
      wells of microtiter plates. Yeast cells of C. neoformans were added in the
      presence of normal human serum, and the plates were incubated at 37 degrees C.
      After 4 h, killing was determined by comparing the quantitative plate counts of
      viable yeast cells in experimental wells with counts in control wells containing
      yeast cells in the absence of leukocytes. No appreciable growth of yeast cells
      occurred in the wells during the incubation period. Both PMNs and monocytes
      effectively killed yeast cells at effector-to-target ratios as low as 1:1,
      although monocytes failed to kill the capsule-free strain 602 at a 1:1 ratio.
      With 9 of 12 strains, PMNs killed C. neoformans more effectively than did
      monocytes. Significant interstrain variation in killing occurred for both
      monocytes and PMNs, and the recent, clinical isolates were more resistant to
      killing by monocytes and PMNs than were the previously characterized strains. The
      extent to which different strains were killed by monocytes and PMNs was not
      consistently related to the size of the capsule or the entire cell. Normal PMNs
      and monocytes are remarkably effective in killing strains of C. neoformans in the
      absence of specific antibody and appear to constitute a significant defense
      mechanism in the peripheral circulation.

PMID- 1987039
TI  - Legionella pneumophila inhibits protein synthesis in Chinese hamster ovary cells.
AB  - Legionella pneumophila is a gram-negative facultative intracellular parasite that
      causes Legionnaires disease. To explore the interactions between L. pneumophila
      and host cells, we have developed a continuous cell line model of infection. We
      show that about 80% of Chinese hamster ovary (CHO) cells were associated with L.
      pneumophila after incubation for 3 h at a multiplicity of infection of 20
      bacteria per cell. Within 3 to 4 h of incubation with L. pneumophila, protein
      synthesis of CHO cells was markedly inhibited, as shown by the reduction of
      incorporation of radiolabeled amino acids into proteins. L. pneumophila did not
      inhibit transport of amino acids or cause degradation of newly synthesized
      proteins in CHO cells. Cytochalasin D blocked internalization of L. pneumophila
      by CHO cells, yet CHO cell protein synthesis was inhibited. These results
      indicated that L. pneumophila could inhibit host protein synthesis from the cell
      exterior. L. pneumophila that had been killed with antibiotics prior to
      incubation with CHO cells still inhibited protein synthesis, indicating that the
      inhibition of CHO cell protein synthesis occurred in the absence of de novo
      protein synthesis by L. pneumophila.

PMID- 1987040
TI  - Interactions between Yersinia enterocolitica and rabbit ileal mucus: growth,
      adhesion, penetration, and subsequent changes in surface hydrophobicity and
      ability to adhere to ileal brush border membrane vesicles.
AB  - Interactions between Yersinia enterocolitica and rabbit ileal mucus were
      examined. Strains carrying the Yersinia virulence plasmid, pYV, adhered to crude
      mucus but not to intestinal luminal contents that had been immobilized on
      polystyrene. Using an Y. enterocolitica O:9 mutant in which the yadA gene
      (formerly called yopA), encoding the high-molecular-weight outer membrane protein
      YadA (formerly called protein P1 or Yop1), had been inactivated and an
      Escherichia coli strain carrying the cloned yadA gene, we demonstrated that the
      ability to adhere to mucus correlated closely to expression of YadA. Thereafter,
      we evaluated possible consequences of binding between pYV-carrying Y.
      enterocolitica O:3 strains and constituents in the mucus layer. pYV-carrying
      strains were able to multiply at a high rate in mucus but not in luminal
      contents, and the ability to adhere to mucus could therefore facilitate bacterial
      colonization of the mucosa. However, we also showed in vitro that mucus acted as
      a barrier for a mucus-adherent, pYV-carrying Y. enterocolitica strain.
      Furthermore, penetration through, or preincubation with, mucus reduced subsequent
      adhesion of the pYV-carrying strain to brush border membrane vesicles without
      simultaneously causing bacterial aggregation. Preincubation with mucus also
      changed the bacterial surface of the same strain from hydrophobic to hydrophilic.
      Immunoglobulins present in mucus did not seem to be of importance for our
      observations. Interaction of Y. enterocolitica with intestinal mucus may thus
      reflect a host defense mechanism that reduces the pYV-mediated adhesion to the
      epithelial cell membrane, possibly by rendering the bacteria less hydrophobic.

PMID- 1987041
TI  - Molecular detection of persistent Borrelia burgdorferi in the urine of patients
      with active Lyme disease.
AB  - Current diagnostic tests for Lyme disease (LD) are dependent upon the host
      serologic response and are insensitive early in infection and, possibly,
      following antibiotic therapy. We cloned a library of Borrelia burgdorferi 297 DNA
      and studied one clone, Ly-1, for its potential in diagnostic and pathogenic
      studies. Using pulsed-field electrophoresis, we demonstrated that Ly-1 is of
      chromosomal origin and estimated that the B. burgdorferi chromosome is
      approximately 1,100 kb in size. The 3.7-kb Ly-1 clone hybridizes with
      geographically diverse strains of B. burgdorferi. No cross hybridization occurs
      with DNA from human cells, Escherichia coli, Staphylococcus aureus, Clostridium
      difficile, or the closely related B. hermsii. We used a dot blot assay to detect
      100 pg of B. burgdorferi DNA. We partially determined the nucleotide sequence of
      Ly-1 and used it to select and synthesize oligonucleotides for use in the
      polymerase chain reaction (PCR). Two different primer pairs were found to amplify
      DNA from nine geographically diverse isolates. We could detect 10 fg (less than
      10 molecules) of B. burgdorferi or less than five spirochetes added to human
      urine. Finally, we were able to use the PCR to detect B. burgdorferi DNA in the
      urine of four of eight patients with suspected active LD (three with arthritis
      and one with neurologic manifestations), all of whom responded to antibiotic
      treatment. In contrast, those patients who were PCR negative either had inactive
      disease or had been appropriately treated and did not respond to additional
      antibiotics, and all four control urine specimens were PCR negative. We conclude
      that B. burgdorferi DNA can be sensitively detected by the PCR with the primers
      and methods we describe and that the urinary tract is a site of persistent
      infection in some cases of human LD, an observation of potential diagnostic and
      pathogenic importance.

PMID- 1987042
TI  - Thrombospondin binds to Staphylococcus aureus and promotes staphylococcal
      adherence to surfaces.
AB  - Bacterial adherence to surfaces is the determining first step in staphylococcal
      infections. Activated platelets mediate adherence of staphylococci to tissues
      during inflammation or infection; however, the molecular mechanisms of this
      interaction are not clearly understood. Thrombospondin, a large multifunctional
      glycoprotein, is the principal platelet-stored glycoprotein. It is secreted upon
      platelet activation and either bound to receptors on the platelet surface or
      released and incorporated into blood clots and extracellular matrices. To
      characterize thrombospondin binding to staphylococci, we incubated
      [125I]thrombospondin with Staphylococcus aureus Cowan 1 in the presence of
      albumin and separated bound and free thrombospondin by centrifugation. We found
      that binding was (i) specific, since it was up to 76% inhibitable and up to 60%
      reversible in the presence of a 100-fold excess of unlabeled thrombospondin, (ii)
      saturable, with an apparent dissociation constant (Kd) of 5.6 x 10(-9) M and a
      maximal number of 2,600 binding sites per microorganism, and (iii) Ca2+
      dependent, since omission of this ion from the medium decreased significantly the
      binding capacity. The binding reaction was insensitive to previous trypsin
      treatment of bacteria, but it was strongly inhibited in the presence of heparin.
      Protein A-negative and -positive strains had similar binding characteristics. To
      determine the promotion of staphylococcal adherence to surfaces by solid-phase
      thrombospondin, we incubated 3H-labeled S. aureus Cowan 1 and 26 pathogenic
      staphylococcal isolates with thrombospondin-coated polymethylmethacrylate disks
      and found that adherence was significantly promoted as a function of adsorbed
      thrombospondin. These results indicate a role for thrombospondin as an important
      mediator of staphylococcal adherence to activated platelets, to blood clots, or
      to extracellular matrices in pyogenic infections.

PMID- 1987043
TI  - Role of bacterial association with Kupffer cells in occurrence of endogenous
      systemic bacteremia.
AB  - Bacteremia in immunocompromised hosts often arises from their endogenous
      intestinal flora. We produced experimental endogenous bacteremia by administering
      cyclophosphamide and ampicillin to conventional and specific-pathogen-free mice.
      The frequencies of bacteremia and mortality in the conventional mice were
      significantly higher than for the specific-pathogen-free mice. Pseudomonas
      aeruginosa was the major pathogen causing systemic bacteremia in conventional
      mice and was associated with a high mortality rate. Morganella morganii caused
      systemic bacteremia in both conventional and specific-pathogen-free mice. In
      contrast, Escherichia coli, enterococci, or other species most often caused
      portal bacteremia only. To determine the mechanism of occurrence of systemic
      bacteremia, we investigated bacterial blood clearance in mice and association
      with murine Kupffer cells, using several bacterial strains isolated from mice
      with bacteremia. Blood clearance rates and the abilities of isolated Kupffer
      cells to associate with bacteria were significantly greater for the organisms
      causing portal bacteremia than for those causing systemic bacteremia. There were
      no significant differences between the blood clearance rates in carrageenan
      treated mice and that in normal mice. Moreover, association at 4 degrees C was
      not different from that at 37 degrees C. The results suggest that blood clearance
      of bacteria reflects bacterial adherence to Kupffer cells and that the resistance
      of bacteria to association with Kupffer cells plays an important role in the
      occurrence of overwhelming systemic bacteremia in this animal model.

PMID- 1987044
TI  - Identification and characterization of an immunodominant 58-kilodalton antigen of
      Aspergillus fumigatus recognized by sera of patients with invasive aspergillosis.
AB  - Sera from 38 patients with invasive aspergillosis were tested by Western
      immunoblotting for the presence of antibodies to antigens of Aspergillus
      fumigatus present in a mycelial extract of the organism. All of the sera
      contained antibodies to an antigen of molecular weight 58,000, which was which
      was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. It
      was the only antigen recognized in approximately 90% of the sera tested. The 58
      kDa antigen is an abundant component of mycelial extracts composing approximately
      50% of the Coomassie blue-stained protein. The antigen also contains
      carbohydrate, since it is stained by the carbohydrate stain periodic acid-Schiff
      and it binds to the lectin concanavalin A. It was purified by immunoaffinity
      chromatography employing a monoclonal antibody directed against an epitope on the
      58-kDa antigen. Analysis of the purified antigen by gas-liquid chromatography
      revealed the presence of mannose, galactose, and glucose residues in a 2:1:2
      ratio. The ratio of protein to carbohydrate is 1.16:1. The protein is slightly
      acidic, containing relatively high quantities of glutamic and aspartic acids,
      glycine, alanine, serine, and threonine. The 58-kDa antigen also contains
      phosphate groups as part of its structure. Serological activity was totally
      destroyed after treatment with sodium metaperiodate and was partially destroyed
      after treatment with pronase. The 58-kDa antigen was not able to hydrolyze
      protein.

PMID- 1987045
TI  - Production and characterization of monoclonal antibodies to a 58-kilodalton
      antigen of Aspergillus fumigatus.
AB  - Eight monoclonal antibodies that recognize a serodiagnostically important 58-kDa
      antigen of Aspergillus fumigatus were produced and partially characterized. 2-7,
      2-12, and 2-14 are of the immunoglobulin M class, and 2-2-1, 2-2-4, 2-2-6, 2-2-9,
      and 2-2-13 are all immunoglobulin G1(kappa) antibodies. Immunoblot analysis with
      A. fumigatus mycelial extract demonstrated that all of the monoclonal antibodies
      recognize a major 58-kDa antigen. The antigen was also detected by immunoblot
      analysis of 4- and 7-day culture filtrate preparations. 2-2-1, 2-2-4, and 2-2-6
      cross-reacted with an antigen of approximately 55 kDa from an extract of Candida
      albicans. 2-7, 2-12, 2-14, and 2-2-4 formed a precipitin band with immunoaffinity
      purified 58-kDa antigen by immunodiffusion. Results from indirect
      immunofluorescence assays with 2-7 and 2-2-9 showed fluorescent staining mainly
      on the surfaces of conidia and hyphae, indicating that the 58-kDa antigen may be
      cell wall associated. 2-2-9 and 2-2-13 and antibodies in patient and immune
      rabbit sera precipitated the [35S]methionine-labeled 58-kDa antigen. The 58-kDa
      antigen immunoprecipitated by each of the antibodies was enzymatically cleaved by
      Staphylococcus aureus V8 protease; one cleavage product, a 35-kDa fragment, was
      generated, indicating that the precipitated antigens share primary structure.
      Immunoblot analysis with an immunoaffinity-purified 58-kDa antigen showed that
      sera from patients with invasive aspergillosis reacted with the same antigen as
      that recognized by the monoclonal antibodies.

PMID- 1987046
TI  - Pulsed-field gel electrophoretic analysis of leptospiral DNA.
AB  - The genomic structures of spirochete species are not well characterized, and
      genetic studies on these organisms have been hampered by lack of a genetic
      exchange mechanism in these bacteria. In view of these observations, pulsed-field
      gel electrophoresis was used to examine the genomes of Leptospira species. Live
      cells, prepared in agarose plugs, were lysed in situ, and the DNA was analyzed
      under different electrophoretic conditions. Pulsed-field gel electrophoresis of
      DNA digested with infrequently cutting restriction enzymes showed that the genome
      of Leptospira interrogans serovar canicola is approximately 3.1 Mb, while that of
      the saprophytic L. biflexa serovar patoc I is 3.5 Mb. DNA forms of approximately
      2,000 and 350 kb which were present in samples from L. interrogans serovars were
      not readily detected in nonpathogenic serovars. Three distinct populations,
      designated type alpha, beta, and gamma, of L. interrogans DNA molecules were
      further analyzed with two-dimensional gel electrophoresis. Evidence suggested
      that two of these DNA forms, type alpha and gamma, were linear structures. Pulsed
      field gel electrophoresis has proven to be a valuable tool with which to size
      bacterial genomes and to take the first steps toward characterization of a form
      of leptospiral DNA which behaves as a linear molecule and which may be related to
      the virulence of L. interrogans.

PMID- 1987048
TI  - Effects of Bordetella pertussis infection on human respiratory epithelium in vivo
      and in vitro.
AB  - Bordetella pertussis infection probably involves attachment to and destruction of
      ciliated epithelial cells, but most previous studies have used animal tissue.
      During an epidemic, nasal epithelial biopsy specimens of 15 children (aged 1
      month to 3 1/2 years) with whooping cough were examined for ciliary beat
      frequency, percent ciliation of the epithelium, and ciliary and epithelial cell
      ultrastructure. In addition, the in vitro effects of filtrates from a 24-h broth
      culture and of tracheal cytotoxin derived from B. pertussis on human nasal tissue
      organ culture were measured. B. pertussis was cultured from nasal swabs from 12
      children. The mean ciliary beat frequency of their nasal biopsy specimens, 11.3
      Hz (range, 10.4 to 13.0 Hz) was similar to that found in biopsy specimens from 10
      normal children (mean, 12.5 Hz; range, 11.8 to 13.5 Hz). The abnormalities of the
      epithelium observed in 14 of 15 patients were a reduction in the number of
      ciliated cells, an increase in the number of cells with sparse ciliation, an
      increase in the number of dead cells, and extrusion of cells from the epithelial
      surface. In vitro, neither culture filtrate nor tracheal cytotoxin had any acute
      effect on ciliary function, but culture filtrate and tracheal cytotoxin (1 and 5
      microM, respectively) caused extrusion of cells from the epithelial surface of
      turbinate tissue, loss of ciliated cells, an increased frequency of sparsely
      ciliated cells, and toxic changes in some cells. These changes were dose
      dependent and progressive, and between 36 and 90 h ciliary beating ceased. The
      observations made with patient tissue confirm that B. pertussis infection damages
      ciliated epithelium, and the in vitro experiments suggest that tracheal cytotoxin
      may be responsible for the abnormalities observed in vivo.

PMID- 1987047
TI  - Antigenicity and immunogenicity of an extract from the cell wall and cell
      membrane of Histoplasma capsulatum yeast cells.
AB  - In order to identify T-cell antigens from Histoplasma capsulatum yeast cells, we
      prepared a detergent extract of the cell wall and cell membrane of yeast-phase H.
      capsulatum G217B and analyzed its antigenicity and immunogenicity. Mice injected
      with viable H. capsulatum yeast cells or with 500 or 1,000 micrograms of the
      extract mounted a delayed-type hypersensitivity response to solubilized cell wall
      and cell membrane. Vaccination with this antigenic preparation conferred a
      protective immune response in mice that were challenged intravenously with H.
      capsulatum yeast cells. The extract induced in vitro proliferation by splenocytes
      from mice injected with either viable yeast cells or the soluble cell wall and
      cell membrane preparation. We also examined the profile of in vitro responses by
      a murine T-cell line and by cloned T cells to soluble cell wall and cell membrane
      by employing the technique of T-cell immunoblotting. Two prominent regions that
      stimulated the T-cell line and cloned T cells were identified. Fractions
      encompassing an area between 53 and 64 kDa caused proliferation by a T-cell line
      and five of six clones. Antigens recognized by the T-cell line and by three of
      six clones were contained in another area that extended from 69 to 82 kDa. The
      data demonstrate that this soluble extract from cell wall and cell membrane
      contains antigens recognized by T cells and mediates protective immunity.
      Moreover, T-cell immunoblotting provides a useful technique for mapping
      immunoreactive molecules from H. capsulatum yeast cells.

PMID- 1987049
TI  - Vaccination of Lewis rats with temperature-sensitive mutants of Mycoplasma
      pulmonis: adoptive transfer of immunity by spleen cells but not by sera.
AB  - Temperature-sensitive mutant vaccines protect rats against Mycoplasma pulmonis
      infection. The role of the humoral or cellular immune response in resistance to
      mycoplasma infection was investigated by adoptive-transfer experiments. Spleen
      cells from Lewis rats vaccinated but not challenged with wild-type organisms
      (vaccinated) and spleen cells from rats vaccinated (or not) and challenged were
      effective in preventing syngeneic recipients from developing respiratory disease.
      There was also a significant reduction in the incidence and number of challenging
      organisms in the respiratory system. In contrast, sera from the same donors had
      no detectable effect on the number of mycoplasmas recovered or on lesion
      development in the respiratory tract. We conclude that cellular immunity rather
      than humoral immunity generated in vaccinated rats confers protection against
      subsequent infection.

PMID- 1987050
TI  - Polymorphism in the aerobactin-cloacin DF13 receptor genes from an enteroinvasive
      strain of Escherichia coli and pColV-K30 is associated only with a decrease in
      cloacin susceptibility.
AB  - We have cloned chromosomal genes mediating the aerobactin iron transport system
      from the enteroinvasive strain Escherichia coli 978-77. The physical map of the
      region spanning the siderophore biosynthesis genes and the upstream portion of
      the receptor gene in strain 978-77-derived clones was identical to the
      corresponding regions in pColV-K30, while the downstream portion was different.
      Recombinant plasmids derived from strain 978-77 encoded a 76-kDa outer membrane
      protein, in contrast to the 74-kDa polypeptide encoded by similar clones derived
      from pColV-K30. No differences were found in the uptake of ferric aerobactin
      mediated by either the 76-kDa- or the 74-kDa-encoding plasmids. In contrast,
      cells containing the 76-kDa-encoding plasmids showed a 16-fold decrease in
      susceptibility to cloacin compared with cells harboring the 74-kDa-encoding
      plasmids. Two classes of chimeric aerobactin receptor genes were constructed by
      exchanging sequences corresponding to the downstream portion from the aerobactin
      receptor gene of both systems. The pColV-K30-978-77 chimeric gene encoded a 76
      kDa outer membrane protein which mediated a low level of cloacin susceptibility,
      whereas the 978-77-pColV-K30 type encoded a protein of 74 kDa determining a level
      of cloacin susceptibility identical to that mediated by pColV-K30.

PMID- 1987051
TI  - Analysis of immunity induced by the affinity-purified 21-kilodalton zygote
      ookinete surface antigen of Plasmodium berghei.
AB  - By using affinity-purified ookinete surface antigen from the rodent malaria
      parasite Plasmodium berghei, a transmission-blocking immunity was induced in
      mice. Groups of mice were immunized via different routes, with total quantities
      of antigen ranging from 0.5 to 40 micrograms (with or without Freund adjuvant).
      Vaccination by the intramuscular route with 20 micrograms of antigen in the
      absence of adjuvant and boosted once with the same amount of protein induced a
      total transmission blockade. Immunoblot analysis confirmed that immune sera
      invariably recognized Pbs21 antigen. The isotype and titer of the anti-Pbs21
      immunoglobulin G (IgG) response was determined by enzyme-linked immunosorbent
      assay. The antibody isotype was predominantly IgG1. The concentration of specific
      anti-Pbs21 IgG reached a peak of 182.45 +/- 92.13 micrograms/ml by week 7
      postimmunization and fell progressively to 38 micrograms/ml at week 34 (at which
      time the transmission was still inhibited by 98%).

PMID- 1987052
TI  - Porphyromonas (Bacteroides) gingivalis fimbrillin: size, amino-terminal sequence,
      and antigenic heterogeneity.
AB  - Bacterial fimbriae mediate cell adhesion and are important in colonization.
      Fimbrial proteins from strains of Porphyromonas (Bacteroides) gingivalis isolated
      from different individuals were compared for their size, amino-terminal sequence,
      and antigenic diversity. Two major protein components of the crude fimbrial
      preparations differed in apparent molecular mass, ranging from 41 to 49 kDa for
      the fimbrillin monomer and from 61 to 78 kDa for the other major protein. The
      amino-terminal sequence of the antigenically related group of proteins of the
      fimbrillin monomer in the 41- to 49-kDa range showed significant homology;
      however, minor sequence heterogeneity was observed, mainly in residues 4 to 6.
      One of the observed amino-terminal sequences, AFGVGDDESKVAKLTVMVYNG, resembled
      the deduced sequence of P. gingivalis 381 (D.P. Dickinson, M. K. Kubiniec, F.
      Yoshimura, and R.J. Genco, J. Bacteriol. 170:1658-1665, 1988). Fimbriae from all
      the strains of P. gingivalis showing this sequence contained a fimbrillin monomer
      of 43 kDa and showed a strong reaction with both polyclonal and monoclonal
      antibodies directed to the fimbriae from P. gingivalis 2561 (381). Fimbriae from
      strains showing amino-terminal sequence variations in residues 4 to 6 (i.e.,
      substitution of VGD with either E or NAG) were more diverse in their molecular
      sizes. Most of these variant fimbriae showed weak reactions with the polyclonal
      antibodies and no reaction with the monoclonal antibodies induced to the fimbriae
      of strain 2561. No correlation could be established between the molecular size
      and immunological reactivity of the fimbrillin monomer of P. gingivalis strains.
      Strains 9-14K-1 and HG 564 not only showed markedly different sequences from the
      other three amino-terminal sequences but also did not react with either
      polyclonal or monoclonal antibodies to the fimbriae of strain 2561. Strains W50,
      W83, and AJW 5 failed to show any immunological reactivity with the antibodies to
      fimbrillin or fimbriae of strain 2561. Fimbriae from different strains revealed
      different immunologic reactions with rabbit antisera to each of the synthetic
      peptides of residues 59-78 (peptide I), 79-100 (peptide J), and 91-108 (peptide
      E) of strain 381. These results suggest that P. gingivalis fimbrillin subunits
      have size, sequence, and antigenic heterogeneity among the strains and that these
      differences may be important in the function and immune reactivities of the
      fimbriae.

PMID- 1987053
TI  - Tandem insertion sequence-like elements define the expression site for variable
      antigen genes of Borrelia hermsii.
AB  - The spirochete Borrelia hermsii avoids the immune response of its mammalian host
      through multiphasic antigenic variation. Serotype specificity is determined by
      variable antigens, Vmp proteins, in the outer membrane. Through nonreciprocal
      recombination between linear plasmids, a formerly silent vmp gene replaces
      another vmp gene downstream from a common expression site. To further
      characterize this activating site, we determined the nucleotide sequence of 6.9
      kb of the common upstream expression region of strain HS1 of B. hermsii.
      Preceding the vmp gene promoter and a poly(dT.dA) run were three imperfectly
      repeated segments of 2 kb. Each of the 2-kb segments contained 1-kb elements with
      inverted repeats of approximately 0.2 kb each at their termini. The potential of
      the 1-kb elements to form stem-and-loop structures was demonstrated by
      heteroduplex analysis. There was no evidence of the presence of the elements
      elsewhere in the genome of B. hermsii. One or more of these elements may confer
      the unidirectionality that characterizes vmp gene switches.

PMID- 1987054
TI  - Interleukin-6 response to deliberate colonization of the human urinary tract with
      gram-negative bacteria.
AB  - Intravesical inoculation of patients with Escherichia coli provided an
      opportunity to examine the interleukin-6 (IL-6) response to a gram-negative
      bacterial urinary tract infection in humans. All patients secreted IL-6 as a
      result of infection. Urinary IL-6 was not continuously secreted but appeared as a
      series of similar peaks during the first 48 h after infection. There was no
      significant difference in the ability to trigger IL-6 secretion between isogenic
      adhering or nonadhering strains, but a threshold concentration of 10(5) bacteria
      per ml of urine was necessary to fully stimulate IL-6 secretion. There was no
      detectable increase in IL-6 levels in the serum of the colonized individuals,
      suggesting mainly local IL-6 production. These results demonstrate that IL-6 is a
      part of the human mucosal response to gram-negative urinary tract infections.

PMID- 1987055
TI  - Genetic control of natural resistance in mouse macrophages regulating
      intracellular Legionella pneumophila multiplication in vitro.
AB  - It is known that Legionella pneumophila proliferates in peritoneal macrophage
      cultures derived from A/J mice but not in macrophage cultures derived from many
      other strains, including C57BL/6 mice. To analyze the genetic control of this
      trait and the location of the Legionella resistance-susceptibility gene, we
      prepared segregating progeny of A/J and C57BL/6 mice and determined the levels of
      susceptibility of individual mice. Peritoneal macrophages were collected by
      injecting thioglycolate medium, and macrophage monolayers were infected in vitro
      with L. pneumophila Philadelphia-1. Counting of colonies on buffered charcoal
      yeast extract agar plates and Gimenez staining of macrophage monolayers were
      carried out daily. There was a 10-fold increase in bacterial burden 1 day after
      infection and a 100-fold increase after 2 days in A/J (susceptible) macrophages.
      The increase in bacterial burden was always less than 10-fold in macrophages from
      C57BL/6 (resistant) progenitors, A/J x C57BL/6 F1 hybrids, and C57BL/6 x F1
      backcross progeny. The ratios of resistant individuals to susceptible individuals
      were 22:6 for F2 progeny and 20:22 for A/J x F1 backcross progeny. The fact that
      the organism did not proliferate in macrophages from B10.A mice demonstrated that
      major histocompatibility antigens did not regulate the macrophage resistance of
      C57BL/6-derived mice. The sex and coat color genes of mice were not linked to the
      resistance-susceptibility gene. We suggest that resistance and susceptibility are
      controlled by a single gene or closely linked genes which are autosomal and that
      the resistance allele is dominant. The results of a comparison of the strain
      distribution pattern of this trait with the distribution pattern of 185 allelic
      markers in A/J x C57BL/6 and C57BL/6 x A/J recombinant inbred strains suggest
      that this susceptibility-resistance gene is located in the proximal part of
      chromosome 15.

PMID- 1987056
TI  - Anaerobic growth of Salmonella typhimurium results in increased uptake by Henle
      407 epithelial and mouse peritoneal cells in vitro and repression of a major
      outer membrane protein.
AB  - The growth of Salmonella typhimurium under anaerobic conditions resulted in its
      greater ability to invade Henle 407 epithelial cells and in greater uptake by
      mouse peritoneal cells in vitro. Anaerobic growth also resulted in the repression
      of at least one major outer membrane protein.

PMID- 1987058
TI  - Slime production by Staphylococcus saprophyticus.
AB  - Only 9 of 30 Staphylococcus saprophyticus strains produced slime in trypticase
      soy broth, while all did so in urine. It was found that urea was essential for
      the production of slime. The pH, the iron concentration, or the presence of sex
      hormones did not affect slime production.

PMID- 1987059
TI  - Median infective dose of Treponema pallidum determined in a highly susceptible
      guinea pig strain.
AB  - The median infective dose of Treponema pallidum subsp. pallidum and the
      production of immunity to reinfection in C4D guinea pigs have been determined
      with 10(1) to 10(6) organisms per infective dose. The mean infective dose is
      10(2) organisms, and immunity--in those animals that demonstrated lesions-
      developed after 4.5 months postinfection.

PMID- 1987057
TI  - Diphosphoryl lipid A obtained from the nontoxic lipopolysaccharide of
      Rhodopseudomonas sphaeroides is an endotoxin antagonist in mice.
AB  - Diphosphoryl lipid A (DPLA) obtained from the nontoxic lipopolysaccharide (LPS)
      of Rhodopseudomonas sphaeroides ATCC 17023 did not induce interleukin-1 release
      by murine peritoneal macrophages. However, it blocked this induction by toxic
      deep-rough chemotype LPS (ReLPS) from Escherichia coli D31m4. Previously, we
      obtained similar results on the induction of tumor necrosis factor (TNF) by
      macrophages. These results showed that DPLA is able to block in vitro the
      induction of two important mediators of gram-negative bacterial sepsis. We then
      wanted to determine whether DPLA could also block the induction of TNF by LPS in
      animals. Mice were treated with 100 micrograms of R. sphaeroides DPLA and
      challenged 60 min later with 1.0 micrograms of ReLPS from E. coli. The serum TNF
      level was measured after 60 min. Treatment of mice with this DPLA blocked the
      rapid and transient rise of TNF caused by ReLPS. This result suggested that R.
      sphaeroides DPLA might be able to protect animals against endotoxin shock caused
      by gram-negative bacterial infection.

PMID- 1987060
TI  - Immunological characterization of Clostridium butyricum neurotoxin and its
      trypsin-induced fragment by use of monoclonal antibodies against Clostridium
      botulinum type E neurotoxin.
AB  - We examined the reactivities of Clostridium butyricum neurotoxin to nine
      monoclonal antibodies against Clostridium botulinum type E neurotoxin which
      recognize the light chain or the amino-terminal half (H-1 fragment) or the
      carboxyl-terminal half (H-2 fragment) of the heavy chain of botulinum neurotoxin.
      Butyricum neurotoxin and its derived chains did not react to two of four
      monoclonal antibodies recognizing the light chain, one of three recognizing the H
      1 fragment, and one of two recognizing the H-2 fragment. The results indicate
      that the immunological difference between the two neurotoxins is not attributable
      to a particular portion of the toxin molecule. The fragment of butyricum
      neurotoxin obtained by prolonged tryptic treatment was found to comprise the
      light chain and H-1 fragment linked together by a disulfide bond.

PMID- 1987061
TI  - Lactose-sensitive and -insensitive cell surface interactions of oral
      Streptococcus milleri strains and actinomyces.
AB  - Of 158 oral Streptococcus milleri strains, 46 exhibited cellular coaggregation
      with the reagent strains of the actinomyces coaggregation groups A, B, and/or E.
      All but 1 of the 33 serotype b, e, f/F, and k/G strains belonged to streptococcus
      coaggregation group 2, and only 14 strains of limited seroclasses (g, i,
      Lancefield group F, or untypeable) appeared to be members of group 5, 3, or 4
      (10, 3, and 1 strain, respectively). Thus, S. milleri infrequently exhibits
      lactose-inhibitable coaggregation with actinomyces.

PMID- 1987062
TI  - Differential expression of Trypanosoma cruzi neuraminidase in intra- and
      extracellular trypomastigotes.
AB  - The developmentally regulated expression of Trypanosoma cruzi neuraminidase in
      culture cells was monitored by immunofluorescence with a monoclonal antibody (TCN
      2) against the enzyme. The results showed that TCN-2 reacted with all
      intracellular trypomastigote forms (NA+) but not with amastigotes.
      Immunoprecipitation of radiolabeled neuraminidase confirmed TCN-2 reactivity with
      trypomastigotes and the specificity of the antibody binding. During exiting from
      the host cells, all trypomastigotes were still NA+. However, when free in the
      extracellular environment, the relative proportion of NA+ parasites declined from
      100% to about 20%, thereby establishing a subpopulation of trypomastigotes which
      did not express enzyme (NA-). The expression of neuraminidase in all
      intracellular trypomastigotes and in only a subpopulation of the extracellular
      counterpart suggests that the enzyme may play a role in parasite exiting from
      infected cells.

PMID- 1987063
TI  - Adherence of Ureaplasma urealyticum to human erythrocytes.
AB  - Ureaplasma urealyticum (four serotypes and two clinical isolates) were
      metabolically labeled with radioactive methionine to a high specific activity.
      Labeling allowed the study of the mechanism of adherence to human erythrocytes.
      The adherence mechanism was complex and partially mediated by proteinaceous
      surface components. The binding sites on the erythrocytes were partially
      sensitive to neuraminidase treatment, and adherence was inhibited by glycophorin
      and dextran sulfate, indicating recognition of sialyl residues and sulfated
      compounds.

PMID- 1987064
TI  - Facilitated isolation, purification, and analysis of glucuronoxylomannan of
      Cryptococcus neoformans.
AB  - Cryptococcus neoformans was cultured in a chemically defined medium. The culture
      was adjusted to 0.25% formaldehyde or autoclaved after 5 days of growth at 35
      degrees C, and a cell-free supernatant was obtained by centrifugation. Solid
      calcium acetate was added to the supernatant to give a 5% solution, and the pH
      was adjusted to approximately 5 with glacial acetic acid. The polysaccharide (PS)
      was precipitated by the addition of 3 volumes of 95% ethanol. The PS was
      dissolved in 0.2 M NaCl, and insoluble calcium salts were solubilized by the
      addition of several drops of glacial acetic acid. The PS solution was treated by
      ultrasonic irradiation for 15 min. This concurrently decreased the molecular
      weight of the PS and reduced the viscosity of the solution. The ultrasonically
      irradiated PS was precipitated by differential complexation with
      hexadecyltrimethylammonium bromide at 23 degrees C, the complex was dissolved in
      1 M NaCl, and the glucuronoxylomannan was precipitated by adding 3 volumes of
      ethanol. The glucuronoxylomannan was dissolved in 1 M NaCl and then
      ultrasonically irradiated for 2 h to reduce the molecular mass to a limiting
      value of approximately 100 kDa (GXMS). The purified GXMS was centrifuged,
      dialyzed, and finally recovered by lyophilization. GXMS was chromatographed on
      DEAE-cellulose at reasonable concentrations without the complication of high
      solution viscosity. The sugar composition and structure of GXMS were determined
      by gas-liquid chromatography, permethylation gas-liquid chromatography-mass
      spectrometry, and 13C nuclear magnetic resonance spectroscopy. The improved
      solution characteristics of GXMS were ideal for the determination of its chemical
      and serological properties.

PMID- 1987065
TI  - Analysis of the immunoglobulin A protease gene of Streptococcus sanguis.
AB  - The amino acid sequence T-P-P-T-P-S-P-S is tandemly duplicated in the heavy chain
      of human immunoglobulin A1 (IgA1), the major antibody in secretions. The
      bacterial pathogen Streptococcus sanguis, a precursor to dental caries and a
      cause of bacterial endocarditis, yields IgA protease that cleaves only the Pro
      Thr peptide bond in the left duplication, while the type 2 IgA proteases of the
      genital pathogen Neisseria gonorrhoeae and the respiratory pathogen Haemophilus
      influenzae cleave only the P-T bond in the right half. We have sequenced the
      entire S. sanguis iga gene cloned into Escherichia coli. A segment consisting of
      20 amino acids tandemly repeated 10 times, of unknown function, occurs near the
      amino-terminal end of the enzyme encoded in E. coli. Identification of a
      predicted zinc-binding region in the S. sanguis enzyme and the demonstration that
      mutations in this region result in production of a catalytically inactive protein
      support the idea that the enzyme is a metalloprotease. The N. gonorrhoeae and H.
      influenzae enzymes were earlier shown to be serine-type proteases, while the
      Bacteroides melaninogenicus IgA protease was shown to be a cysteine-type enzyme.
      The streptococcal IgA protease amino acid sequence has no significant homology
      with either of the two previously determined IgA protease sequences, that of type
      2 N. gonorrhoeae and type 1 H. influenzae. The differences in both structure and
      mechanism among these functionally analogous enzymes underscore their role in the
      infectious process and offer some prospect of therapeutic intervention.

PMID- 1987066
TI  - Cloning and sequence of the gene for heat shock protein 60 from Chlamydia
      trachomatis and immunological reactivity of the protein.
AB  - We isolated and sequenced the gene for the chlamydial heat shock protein 60 (HSP
      60) from a Chlamydia trachomatis genomic library by molecular genetic methods.
      The DNA sequence derived revealed an operon-like gene structure with two open
      reading frames encoding an 11,122- and a 57,956-Da protein. The translated amino
      acid sequence of the larger open reading frame showed a high degree of homology
      with known sequences for HSP-60 from several bacterial species as well as with
      plant and human sequences. By using the determined nucleotide sequence, fragments
      of the gene were cloned into the plasmid vector pGEX for expression as fusion
      proteins consisting of glutathione S-transferase and peptide portions of the
      chlamydial HSP-60. HSP-60 antigenic identity was confirmed by an immunoblot with
      anti-HSP-60 rabbit serum. Sera from patients that exhibited both high
      antichlamydial titers and reactivity to chlamydial HSP-60 showed reactivity on
      immunoblots to two fusion proteins that represented portions of the carboxyl
      terminal half of the molecule, whereas fusion proteins defining the amino
      terminal half were nonreactive. No reactivity with the fusion proteins was seen
      with sera from patients that had been previously screened as nonreactive to
      native chlamydial HSP-60 but which had high antichlamydial titers. Sera from
      noninfected control subjects also exhibited no reactivity. Definition of
      recognized HSP-60 epitopes may provide a predictive screen for those patients
      with C. trachomatis infections who may develop damaging sequelae, as well as
      providing tools for the study of immunopathogenic mechanisms of Chlamydia-induced
      disease.

PMID- 1987067
TI  - Protection of gerbils from amebic liver abscess by immunization with the
      galactose-specific adherence lectin of Entamoeba histolytica.
AB  - No protective antigens from Entamoeba histolytica have been previously defined.
      We tested the ability of the galactose-specific adherence lectin of E.
      histolytica to elicit a protective immune response in conjunction with Freund's
      incomplete and complete adjuvants. The gerbil (Meriones unguiculatus) model of an
      experimental amebic liver abscess was used. Gerbils were immunized
      intraperitoneally or subcutaneously with 10 micrograms of the affinity-purified
      lectin in complete Freund's adjuvant and then at 2 and 4 weeks with 10 micrograms
      of the lectin in incomplete Freund's adjuvant. All of the immunized animals
      developed antilectin antibody titers of greater than 1/1,024 as measured by a
      radioimmunoassay. The gerbil antilectin antibodies were shown by Western
      immunoblotting to be directed to the heavy subunit but not the light subunit of
      the lectin. Immune gerbil sera inhibited amebic adherence by 100% at a 1/10
      dilution. Immune and control gerbils were challenged at 6 weeks by the
      intrahepatic injection of 5 x 10(5) E. histolytica trophozoites. Four independent
      trials demonstrated complete protection from amebic liver abscess formation in
      67% of lectin-immunized gerbils. Unexpectedly, liver abscess weights were
      significantly higher in the gerbils that failed to become immune than in the
      control animals. Our results demonstrate that the galactose lectin is a
      protective antigen and provide an immune-animal model to study the mechanisms of
      protection and potential disease exacerbation conferred by the antilectin immune
      response.

PMID- 1987068
TI  - Intracellular and extracellular enzymatic deacylation of bacterial endotoxin
      during localized inflammation induced by Escherichia coli.
AB  - Acyloxyacyl hydrolase (AOAH), an enzyme that removes the secondary acyl chains of
      gram-negative bacterial lipid A (endotoxin), has been identified previously in
      human neutrophils and mouse macrophages. We report here that bovine leukocytes
      also contain AOAH activity. Although bovine AOAH deacylates bacterial
      lipopolysaccharide in a manner similar to human AOAH, it is active in vitro over
      a broader pH range, from 4.0 to 7.0. By using Escherichia coli infection of the
      bovine mammary gland as a model of localized gram-negative bacterial disease and
      associated tissue inflammation, AOAH activity per leukocyte increased. In
      addition, AOAH activity increased in the cell-free portion of infected mammary
      secretions. These data indicate that AOAH activity increases in leukocytes
      associated with inflammation induced by gram-negative bacteria and provide
      additional evidence of its potential involvement in the defense against the
      effects of bacterial endotoxin.

PMID- 1987069
TI  - The rcsA gene of Klebsiella pneumoniae O1:K20 is involved in expression of the
      serotype-specific K (capsular) antigen.
AB  - In Klebsiella pneumoniae, the ability to synthesize large amounts of capsular
      polysaccharide is an important correlate of virulence. We report the cloning of
      rcsA from K. pneumoniae serotype O1:K20 and demonstrate that rcsA is involved in
      the expression of the K antigen capsule. We have determined the nucleotide
      sequence for the rcsA gene from K. pneumoniae K20 and shown it to be identical to
      the sequence reported previously for rcsA from strain K21 (Allen et al., J. Gen.
      Microbiol. 133:331-340, 1987). Southern hybridization results indicate that this
      gene is widely distributed among different Klebsiella K serotypes. When cloned
      into Escherichia coli K-12, the K. pneumoniae rcsA gene caused a mucoid
      phenotype, resulting from the activation of colanic acid synthesis. Activation of
      colanic acid synthesis was not dependent on growth at low temperatures (less than
      or equal to 30 degrees C). The K. pneumoniae rcsA gene complemented E. coli K-12
      rcsA mutations but could not complement defects in rcsB, suggesting that RcsA may
      be functionally homologous in these bacteria. The cloned rcsA gene also
      complemented a defect in nonmucoid strain K20 derivatives that normally produced
      only trace amounts of K20 antigen and were unable to assemble a wild-type
      capsular structure. Mutants that were K20-deficient were not complemented. The K
      antigen capsule of K. pneumoniae therefore joins a growing list of polysaccharide
      synthetic systems in which "RcsA-like" proteins are involved.

PMID- 1987070
TI  - Role of L3T4+ and 38+ T-cell subsets in resistance against infection with
      Treponema pallidum subsp. pertenue in hamsters.
AB  - The protective immunity conferred by T-cell subsets against infection with
      Treponema pallidum subsp. pertenue was studied. We demonstrated that hamster T
      cells can be separated into two subsets by monoclonal antibody (MAb) GK 1.5 (anti
      L3T4) and MAb 38. Eighty-five percent of hamster thymocytes were L3T4+ and 87%
      were 38+ cells; 84% were dual positive for MAbs anti-L3T4 and 38. In the
      peripheral lymph nodes, however, the L3T4+ and 38+ T cells were mutually
      exclusive according to two-color immunofluorescence analysis. The two T-cell
      subsets were found to be functionally distinct according to their secretion of
      interleukin 2 (IL-2) when stimulated with concanavalin A. The L3T4+ cells
      secreted IL-2 and had characteristics of T helper cells, while the 38+ cells did
      not secrete IL-2 and appeared to be T cytotoxic-suppressor cells. Transfer of 4 x
      10(6) helper or cytotoxic-suppressor T lymphocytes from T. pallidum subsp.
      pertenue-immune hamsters protected irradiated naive hamsters against challenge
      with this subspecies. IL-2 production could still be detected in the irradiated
      recipients 12 days after irradiation of naive recipients, although at a low
      level. This suggests that the remaining lymph node cells could support the
      survival and expansion of the infused cytotoxic-suppressor T cells. No
      accumulation of macrophages was observed in regional lymph nodes of immune T-cell
      recipients within 10 days of infection. Instead, there was an influx of
      polymorphonuclear neutrophils in all animals injected with T. pallidum subsp.
      pertenue. This report demonstrates that hamster T cells can be separated into two
      phenotypically and functionally distinct subsets and that both T-cell subsets
      confer protection against challenge with T. pallidum subsp. pertenue.

PMID- 1987071
TI  - Binding of a Streptococcus mutans cationic protein to kidney in vitro.
AB  - An 8-kDa protein, with binding activity for heparin and heparan sulfate of basal
      laminae of animal tissues, was isolated from Streptococcus mutans MT703 and
      purified to homogeneity. Binding of radioiodinated 8-kDa protein to rabbit kidney
      tissue in vitro showed a high degree of specificity, as indicated by saturation
      kinetics, time dependence, and competitive inhibition by unlabeled protein.
      Binding activity for kidney tissue was competitively inhibited by selected
      glycosaminoglycans and polyanions in the following order: heparin greater than
      dextran sulfate greater than heparan sulfate greater than chondroitin sulfate
      greater than lipoteichoic acid greater than keratan sulfate greater than
      hyaluronic acid. Binding of the streptococcal protein to rabbit kidney tissue was
      also strongly inhibited by protamine sulfate, polylysine, and a random copolymer
      of lysine and alanine. Among the monosaccharides tested at 50 mM, glucosamine 2,3
      or 2,6-disulfate, glucuronic acid, glucose 6-phosphate, and glucose 6-sulfate
      inhibited 50% or more of the binding activity, whereas N-acetylglucosamine 3
      sulfate, glucosamine 6-sulfate, N-acetyl-glucosamine, N-acetylgalactosamine, N
      acetylneuraminic acid, and a selection of neutral sugars were not inhibitory. The
      heparin-binding protein was detected on the cell wall of S. mutans and in the
      culture medium following growth. Several other species of streptococci produce an
      immunologically related protein of similar size.

PMID- 1987072
TI  - Immunogenicity of Actinobacillus pleuropneumoniae outer membrane proteins and
      enhancement of phagocytosis by antibodies to the proteins.
AB  - To determine the opsonic effect of antibodies to Actinobacillus (Haemophilus)
      pleuropneumoniae outer membrane proteins on phagocytosis by porcine
      polymorphonuclear leukocytes (PMN), we separated the integral outer membrane
      proteins (IOMPs) by Triton X-114 extraction. Four major IOMPs with molecular
      masses of 76, 50, 39, and 29 kDa were detected by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. These IOMPs were found to be essentially free
      of endotoxin in the Limulus amebocyte lysate assay. The 76-kDa protein exhibited
      a more intensely stained electrophoresis band when isolated from iron-restricted
      cultures, and a new band at 105 kDa was present in the whole-membrane fraction
      but not in the integral fraction, indicating that the 105-kDa iron-repressible
      protein is a peripheral membrane protein. The 76-, 50-, and 39-kDa proteins were
      shown to be surface exposed, since antibodies to these IOMPs could be absorbed
      out of convalescent-phase sera by whole cells. Percentages of phagocytosis by
      porcine PMN of A. pleuropneumoniae opsonized with convalescent-phase sera,
      convalescent-phase sera absorbed with IOMPs, or convalescent-phase sera absorbed
      with whole cells were 46.75, 21.81, and 7.96%, respectively. These results
      demonstrate that antibodies to IOMPs of A. pleuropneumoniae serve as important
      opsonins in phagocytosis by porcine PMN.

PMID- 1987073
TI  - Evidence for peptidoglycan absorption in rats with experimental small bowel
      bacterial overgrowth.
AB  - Surgical creation of jejunal self-filling blind loops (SFBL) causes small bowel
      bacterial overgrowth which is associated with hepatobiliary inflammation in the
      susceptible Lewis and Wistar rat strains. Since hepatic injury occurs when small
      bowel anaerobic bacterial concentrations are increased 4 to 6 log10 units per ml
      and hepatic bacterial cultures are negative, we postulate that the inflammation
      is caused by absorption of phlogistic cell wall polymers originating from
      bacteria within the loop. To demonstrate absorption of bacterial cell wall
      polymers, we measured plasma and hepatic levels of immunoreactive peptidoglycan
      polysaccharide (PG-PS) following intraluminal injection as well as anti-PG
      antibodies as an indirect measure of absorption and/or accumulation of endogenous
      PG. PG-PS purified from group A streptococci was detected in plasma by enzyme
      linked immunosorbent assay after intraluminal injection; rats with SFBL showed
      significantly more uptake into plasma and the liver than sham-operated rats or
      SFBL rats which were treated with metronidazole (P less than 0.025). Total plasma
      immunoglobulin A (IgA), IgG, and IgM levels did not differ among sham-operated
      rats and those with self-emptying blind loops or SFBL, but plasma anti-PG IgA (P
      less than 0.05), IgG, and IgM (P less than 0.01) levels were increased in rats
      with SFBL. Metronidazole and tetracycline prevented the elevation of anti-PG
      antibody, but gentamicin and polymyxin B did not. Anti-lipid A, anti-soy protein,
      and anti-chow antibodies in plasma were not consistently increased in rats with
      SFBL indicating the lack of a generalized antibody response to luminal antigens.
      These data suggest that PG from normal flora bacteria is absorbed from the
      intestinal lumen and that mucosal injury and/or increased luminal concentrations
      of PG, such as those induced by small bowel bacterial overgrowth, lead to
      enhanced absorption of potentially inflammatory bacterial polymers.

PMID- 1987074
TI  - Detection of immunoglobulin A1 protease-induced Fab alpha fragments on dental
      plaque bacteria.
AB  - The mechanisms by which immunoglobulin A1 (IgA1) protease activity may enable
      bacteria to evade the effect of specific secretory IgA (S-IgA) antibodies are not
      clear. A possibility which has received indirect experimental support is that
      bacteria, as a consequence of the protease activity, become coated with
      incompetent Fab alpha fragments instead of with intact antibody molecules. Using
      a combination of nonreducing sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis and immunoblotting, we detected Fab alpha fragments not only on
      oral streptococci (Streptococcus sanguis and Streptococcus gordonii) incubated in
      saliva but also on the bacteria in incipient dental plaque. These results are of
      relevance to our previous observation that IgA1 protease activity may neutralize
      the ability of S-IgA antibodies to inhibit the adherence of oral streptococci to
      saliva-coated hydroxyapatite.

PMID- 1987075
TI  - Efficacy of recombinant leukotoxin in protection against pneumonic challenge with
      live Pasteurella haemolytica A1.
AB  - The recombinant leukotoxin (rLKT) of the bacterium Pasteurella haemolytica A1 was
      examined for its ability to protect cattle from experimental challenge with
      logarithmic-phase P. haemolytica. Six different vaccines were utilized in the
      experiment: P. haemolytica culture supernatant, P. haemolytica culture
      supernatant enriched with rLKT, rLKT alone, P. haemolytica culture supernatant
      enriched with Escherichia coli supernatant not containing LKT, E. coli
      supernatant alone, and phosphate-buffered saline. rLKT alone showed no protective
      capacity against development of clinical signs of respiratory disease or against
      development of postmortem lung lesions after experimental challenge. It was,
      however, shown to enhance the efficacy of the culture supernatant vaccine and
      decrease clinical signs and pneumonic lesions. The complexity of protective
      immunity in this disease is emphasized in this study, and, although LKT is an
      important virulence factor of the organism, an immune response to LKT alone does
      not protect animals against disease.

PMID- 1987076
TI  - Purification and characterization of Streptococcus adjacens (nutritionally
      variant Streptococcus serotype II) group antigen.
AB  - Nutritionally variant streptococci (NVS) possess amphiphiles which are
      serologically distinct from lipoteichoic acid and which serve as group-specific
      antigens for NVS. The objective of this study was to purify and characterize the
      NVS serotype II (Streptococcus adjacens) amphiphile. Amphiphile was isolated from
      stationary-phase culture supernatants of NVS strain 81 (NVS serotype II). Phenol
      water extracts of culture supernatants were subjected to hydrophobic interaction
      chromatography and gel filtration chromatography. A homogeneous preparation of
      amphiphile (22 mg; 8.5 x 10(6) hemagglutination units) was recovered, and its
      approximate molecular size (23,000 to 24,000 Da) and chemical composition were
      determined. Purified S. adjacens amphiphile contained phosphorus, ribitol,
      galactose, galactosamine, alanine, and fatty acids in molar ratios of
      1.00:0.88:1.39:1.10:0.08:0.24. Since ribitol, galactose, and galactosamine were
      the primary carbohydrate components, the amphiphile may exist as a polyribitol
      phosphate with galactose and galactosamine substituents. Preliminary structural
      analysis demonstrated the presence of phosphodiester bonds within the amphiphile
      structure. Finally, the amphiphile serves as the S. adjacens group antigen.

PMID- 1987077
TI  - Contribution of a 28-kilodalton membrane protein to the virulence of Haemophilus
      influenzae.
AB  - A Haemophilus influenzae b (Hib) membrane protein with a molecular mass of 28 kDa
      bound polyclonal antisera raised against a highly purified Hib fimbrial subunit.
      We cloned the gene encoding this protein and found that the gene was expressed in
      Escherichia coli. DNA sequence analysis identified an 843-bp open reading frame
      which predicted a 26.78-kDa protein with an amino-terminal signal sequence and a
      mature protein with 70% similarity to the 28-kDa lipoprotein of E. coli (F. Yu,
      S. Inouye, and M. Inouye, J. Biol. Chem. 261:2284, 1986). Colony blot
      hybridization analysis with an intergenic probe of the cloned gene demonstrated
      that 29 of 32 H. influenzae strains hybridize with this gene. Insertion of a
      chloramphenicol acetyltransferase gene into the open reading frame inactivated
      expression of the 28-kDa protein in E. coli. Isogenic Hib strains were derived by
      marker exchange mutagenesis to generate mutants which no longer expressed the 28
      kDa protein as recognized with Western immunoblot analysis. There was no
      difference in the rate of nasopharyngeal colonization of infant rats or monkeys
      by the isogenic mutants which lacked the 28-kDa protein compared with
      colonization by the wild-type strain. In contrast, the frequency of invasion and
      density of bacteremia in infant rats caused by the isogenic mutants were reduced
      relative to those caused by the wild-type Hib strain. We conclude that this 28
      kDa outer membrane protein aids transepithelial invasion of type b strains but is
      not essential.

PMID- 1987079
TI  - Monoclonal antibody characterization of a leukoagglutinin produced by
      Renibacterium salmoninarum.
AB  - Renibacterium salmoninarum causes a chronic disease of salmonid fish known as
      bacterial kidney disease. High concentrations of bacterially produced
      extracellular protein (ECP) are present in plasma, kidney, and spleen tissue of
      naturally and experimentally infected fish. ECP agglutinated salmonid leukocytes
      in vitro at concentrations which correspond to levels found in highly infected
      fish. Association of biological activity with the structure of the major protein
      constituent of ECP, p57, was accomplished by monoclonal antibody (MAb) analysis.
      Location of the antigenic binding sites recognized by the MAbs was determined by
      two-dimensional electrophoresis and Western immunoblotting of the proteolytic
      breakdown fragments of p57. Eight MAbs have been classified into three groups on
      the basis of their differential recognition of these proteolytic breakdown
      products. Group I MAbs bound a region proximal to the amino terminus of the
      protein. Two of these MAbs were also able to block leukoagglutinating activity.
      Group III MAbs bound to a region associated with the bacterial cell surface,
      while group II MAbs bound a region between group I and group III. These analyses
      have allowed the identification of potential structural and functional regions of
      p57.

PMID- 1987078
TI  - Characterization of cell envelope proteins of Staphylococcus epidermidis cultured
      in human peritoneal dialysate.
AB  - The cell envelope protein profiles of Staphylococcus epidermidis cultured in used
      human peritoneal dialysate (HPD) differed markedly from those of cells cultured
      in nutrient broth. Compared with broth-grown cells, many cell wall proteins were
      repressed in HPD, although three proteins of 42, 48, and 54 kDa predominated and
      an iron-repressible 130-kDa protein was induced. Growth in HPD also resulted in
      expression of two cell membrane proteins of 32 and 36 kDa which were iron
      repressible. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and
      immunoblot analysis using monospecific polyclonal antisera raised against the 32-
      and 36-kDa proteins revealed considerable antigenic and molecular mass homology
      among 12 S. epidermidis isolates from patients with continuous ambulatory
      peritoneal dialysis-related peritonitis. The 32-kDa antiserum also cross-reacted
      with a 32-kDa S. aureus cell membrane protein. Immunoblots of S. epidermidis cell
      walls and membranes were also probed with normal human serum and serum and HPD
      from continuous ambulatory peritoneal dialysis patients. While the cell wall
      proteins of S. epidermidis appeared to be relatively poorly immunogenic, the 32-
      and 36-kDa membrane proteins reacted strongly with antibodies present in each of
      the body fluids evaluated. These results suggest that the highly conserved 32-
      and 36-kDa iron-repressible proteins are expressed during growth in vivo and may
      be involved in iron transport, since all 12 S. epidermidis strains examined also
      produced iron chelators.

PMID- 1987080
TI  - Effect of lysozyme on glucose fermentation, cytoplasmic pH, and intracellular
      potassium concentrations in Streptococcus mutans 10449.
AB  - Several previous findings have suggested that the cationic nature of lysozyme is
      a major factor in its bactericidal activity. Since a number of cationic proteins
      or peptides have been reported to cause membrane damage in bacteria, we
      investigated the effect of lysozyme on glucose fermentation and intracellular pH
      and K+ in Streptococcus mutans under conditions in which lysis does not occur.
      Results showed that lysozyme and poly-D-lysine (PDL) cause inhibition of glucose
      fermentation at pH 5.5 in a dose-dependent manner. Human placental lysozyme and
      hen egg-white lysozyme exhibited similar inhibitory potency on glucose
      fermentation. Both lysozyme and PDL caused a marked acidification of the
      cytoplasm of S. mutans. However, when cytoplasmic pH was examined as a function
      of fermentation rate, the relationship was similar regardless of the presence or
      absence of lysozyme or PDL. Therefore, acidification of the cytoplasm appeared to
      not depend specifically on lysozyme or PDL. In contrast, the same relationship
      between the profound loss of intracellular K+, when fermenting cells were exposed
      to either lysozyme or PDL, and the fermentation rate was not exhibited in the
      controls. These results indicate that lysozyme and PDL specifically affected the
      ability of the cells to maintain intracellular K+. We concluded that lysozyme and
      PDL indeed perturb membrane function, perhaps in a selective manner. Furthermore,
      the similarity in action of lysozyme and the cationic homopolypeptide PDL
      supports the notion that the cationic property of lysozyme indeed plays a
      significant role in its antibacterial activity.

PMID- 1987081
TI  - Attachment of Trypanosoma cruzi to mammalian cells requires parasite energy, and
      invasion can be independent of the target cell cytoskeleton.
AB  - We have previously shown that the binding of Trypanosoma cruzi trypomastigotes to
      glutaraldehyde-fixed mammalian cells has the characteristics of a receptor
      mediated process and that it mimics the attachment step of the invasion of live
      cells by this parasite. In this study we examined the metabolic requirements for
      the attachment of trypomastigotes to glutaraldehyde-fixed fibroblasts. The
      attachment of trypomastigotes to fixed cells is prevented when the energy
      conservation mechanisms are inhibited with the drugs 2-deoxyglucose, sodium
      azide, antimycin, crystal violet, oligomycin, N,N'-dicyclohexylcarbodiimide, and
      carbonyl cyanide 3-chlorophenylhydrazone. However, under the same experimental
      conditions, the movement of parasites is not significantly affected. Several of
      these drugs totally inhibit the penetration of the parasite into live target
      cells. We conclude that the attachment of trypomastigotes to mammalian cells is
      an active process that requires trypomastigote energy. In addition, we present
      evidence that penetration into nonphagocytic cells can also be an active process.
      Trypomastigotes can be seen in scanning electron micrographs traversing extended
      lamellipodia and entering paraformaldehyde-fixed epithelial cells. Cytochalasin
      D, a drug that disrupts microfilaments and prevents the formation of plasma
      membrane extensions mediated by actin, had little or no effect on trypomastigote
      invasion, while it inhibited Salmonella entry into epithelial cells.

PMID- 1987082
TI  - Inhibition of bactericidal and bacteriolytic activities of poly-D-lysine and
      lysozyme by chitotriose and ferric iron.
AB  - In a previous report from this laboratory (N. J. Laible and G. R. Germaine,
      Infect. Immun. 48:720-728, 1985), evidence was presented to suggest that the
      bactericidal actions of both reduced (i.e., muramidase-inactive) human placental
      lysozyme and the synthetic cationic homopolymer poly-D-lysine involved the
      activation of a bacterial endogenous activity that was inhibitable by N,N',N"
      triacetylchitotriose (chitotriose). In the present investigation however, we
      found that the bactericidal and bacteriolytic action of poly-D-lysine could be
      prevented only by some commercially available chitotriose preparations and not by
      others. Analysis by physical and chemical methods failed to distinguish
      protective chitotriose (CTa) and nonprotective chitotriose (CTi) preparations.
      CTi and CTa preparations displayed equal capacities to competitively inhibit
      binding of [3H]chitotriose by immobilized lysozyme and were indistinguishable in
      their abilities to block the lytic activity of lysozyme against Micrococcus
      lysodeikticus cells. Elemental analysis revealed significantly higher levels of
      phosphorus, calcium, iron, sodium, manganese, and copper in CTa. Removal of
      metals from CTa by chelate chromatography completely abolished the poly-D-lysine
      protective capacity. Of the metals detected, only ferric iron (5 to 10 microM)
      mimicked the protective action of CTa. A Fe(III) concentration of 50 microM was
      required to inhibit lysozyme (5 micrograms/ml). Both Fe(III) and CTa (but not
      CTi) quantitatively blocked the labeling of poly-D-lysine by fluorescamine,
      suggesting that the primary amino groups of the lysine residues participate in
      iron binding. Thus, it appears that the poly-D-lysine-protective capacity of
      certain chitotriose preparations was due not to the chitotriose itself but to
      contaminating metal ions which interact directly with the polycationic agent. In
      contrast, Fe(III) cannot account for inhibition of either the bactericidal or
      bacteriolytic activity of lysozyme by chitotriose.

PMID- 1987083
TI  - Intracellular localization of Borrelia burgdorferi within human endothelial
      cells.
AB  - The later stages of infection by the Lyme disease pathogen, Borrelia burgdorferi,
      are characterized by the persistence of the organism in individuals possessing a
      strong anti-Borrelia immune response. This suggests that the organism is
      sequestered in a tissue protected from the immune system of the host or there is
      a reservoir of the organism residing within the cells of the host. In this
      report, the ability of B. burgdorferi to gain entrance into human umbilical vein
      endothelial cells was explored as a model for invasion. Incubation of B.
      burgdorferi with human umbilical vein endothelial cells at ratios ranging from
      200:1 to 5,000:1 resulted in the intracellular localization of 10 to 25% of B.
      burgdorferi in 24 h. The intracellular location of the spirochetes was
      demonstrated by the incorporation of radiolabeled B. burgdorferi into a trypsin
      resistant compartment and was confirmed by double-immunofluorescence staining
      which differentiated intracellular from extracellular organisms. Actin-containing
      microfilaments were required for the intracellular localization, indicating that
      the host cell participates in the internalization process. Activation of
      endothelial cells by agents known to increase the expression of several adhesion
      molecules had no effect on the interaction of B. burgdorferi with the endothelial
      monolayer. This indicates that the endothelial receptor for B. burgdorferi is
      constitutively expressed and that internalization is not dependent upon adhesion
      molecules whose expression is induced by inflammatory mediators. The
      demonstration of B. burgdorferi within endothelial cells suggest that
      intracellular localization may be a potential mechanism by which the organism
      escapes from the immune response of the host and may contribute to persistence of
      the organism during the later stages of Lyme disease.

PMID- 1987084
TI  - Enhancement of lipopolysaccharide-induced tumor necrosis factor production in
      mice by carrageenan pretreatment.
AB  - Tumor necrosis factor (TNF) is a cytokine which mediates endotoxin shock and
      causes multiple organ damage. It is thought that macrophage (MP) activation is
      necessary to increase lipopolysaccharide (LPS)-induced TNF production and
      lethality. Carrageenan (CAR) is sulfated polygalactose which destroys MP; it is
      used as a MP blocker. We found that CAR pretreatment can increase both endotoxin
      induced TNF production and the mortality rate in mice. The ddY mice (7 to 8 weeks
      old) were injected intraperitoneally with CAR (5-mg dose) and challenged
      intravenously with LPS 24 h later. Without CAR pretreatment, LPS doses of less
      than 10 micrograms did not induce TNF in sera. After pretreatment, however, about
      3 x 10(3) to 4 x 10(4) U of TNF per ml was produced after LPS injection at doses
      of 0.1 to 10 micrograms, respectively. TNF production was significantly increased
      by CAR pretreatment at LPS doses of more than 10 micrograms. CAR pretreatment
      rendered the mice more sensitive to the lethal effect of LPS; 50% lethal doses of
      LPS in CAR-pretreated mice and nonpretreated mice were 26.9 and 227 micrograms,
      respectively. The mortality of the two groups was significantly different at
      doses of 50, 100, and 200 micrograms of LPS. CAR increased LPS-induced TNF
      production and mortality within 2 h, much earlier than MP activators, which
      needed at least 4 days. Our results made clear that TNF production is enhanced
      not only by a MP activator but also by a MP blocker.

PMID- 1987085
TI  - Effect of sulfide ions on complement factor C3.
AB  - In infected sites such as the gingival pockets of patients with periodontal
      disease, sulfide levels up to 1 mmol/liter may be reached. There is little
      information, however, on how sulfide may interact with the host defense. In a
      previous study (R. Claesson, M. Granlund-Edstedt, S. Persson, and J. Carlsson,
      Infect. Immun. 57:2776-2781, 1989), it was shown that polymorphonuclear
      leukocytes were able to kill bacteria in the presence of 1 mM sulfide. However,
      sulfide seemed to interfere with the opsonization of the bacteria. It has been
      claimed that sulfide may be toxic by splitting disulfide bonds of proteins. In
      the present study, serum was exposed to 2 mM sulfide under anaerobic conditions,
      and the capacity of sulfide to split disulfide bonds of 10 serum proteins
      involved in opsonization was evaluated by sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis and immunodetection of the proteins after blotting. Sulfide
      had a low capacity to split the disulfide bonds of most proteins. Sulfide had,
      however, a pronounced effect on the complement component C3 in the form of C3bi.
      Sulfide released the C-terminal region of the alpha chain from C3bi. When C3
      opsonizes bacteria, it is this region of C3bi which binds to complement receptor
      3 (CR3) of the polymorphonuclear leukocytes. If sulfide has the same effect on
      C3bi deposited on the bacterial surface as it has on C3bi in solution, it will
      annihilate the very important contribution of C3bi to opsonization.

PMID- 1987086
TI  - Lipopolysaccharide from Klebsiella pneumoniae inhibits Na+ absorption in canine
      tracheal epithelium.
AB  - The effect of lipopolysaccharide (LPS) from Klebsiella pneumoniae on the
      bioelectric properties of canine cultured tracheal epithelium was examined. LPS
      decreased short-circuit current (Isc), and its effects on Isc were reduced when
      Isc was inhibited by amiloride and indomethacin. We speculate that LPS may
      selectively inhibit Na+ absorption through the inhibition of prostaglandin
      synthesis by airway epithelium.

PMID- 1987087
TI  - Susceptibility of mast cell-deficient W/Wv mice to Cryptosporidium parvum.
AB  - Mast cell-deficient W/Wv infant mice were similar to normal mice in their
      susceptibility to and recovery from infection with the intestinal protozoan
      Cryptosporidium parvum. W/Wv adult mice were significantly more susceptible to
      primary infection than were normal adult mice, but both groups recovered at a
      similar rate.

PMID- 1987088
TI  - Sequence analysis of the gene encoding the Chlamydia pneumoniae DnaK protein
      homolog.
AB  - The antigen-coding region of a 4.2-kb PstI fragment of Chlamydia pneumoniae
      (pLC3), which encodes a 75-kDa immunoreactive protein recognized during human C.
      pneumoniae infection, was localized to a 2.0-kb EcoRI fragment. This subclone
      expressed an immunoreactive fusion protein of ca. 82 kDa. Nucleotide sequence
      analysis of the C. pneumoniae gene revealed that it consisted of a 1,980-base
      open reading frame with an inferred 71,550-Da protein of 660 amino acids.
      Putative Escherichia coli-like promoters and a ribosomal binding site were
      located in the 5' upstream region, and an 11-base dyad forming a stable stem-loop
      structure following two in-frame stop codons was identified. The C. pneumoniae 75
      kDa protein is a member of the hsp70 family of heat shock proteins and has 87%
      amino acid similarity with the Chlamydia trachomatis protein.

PMID- 1987089
TI  - Protective immunity to heartwater (Cowdria ruminantium infection) is acquired
      after vaccination with in vitro-attenuated rickettsiae.
AB  - A Senegalese (S) stock of Cowdria ruminantium was passaged on bovine umbilical
      endothelial cells with an average interval of 13.9 days (range, 8 to 34 days)
      between passages. The virulence of infected bovine umbilical endothelial cultures
      was tested in susceptible goats and sheep by intravenous inoculation of culture
      supernatant from passages 2 (51 days in vitro), 3 (69 days), 11 (229 days), 14
      (264 days), and 16 (291 days). Both animals inoculated with passages 2 and 3 died
      of heartwater. However, clinical reactions were completely absent in goats and
      sheep that were inoculated with C. ruminantium from passages 11, 14, and 16. High
      antibody titers were detected, with immunofluorescence in all vaccinated animals,
      and a strong signal was found against a 32-kDa Cowdria protein in Western blots
      (immunoblots). Moreover, the vaccinated animals proved solidly immune when
      challenged with virulent Cowdria sp.-infected blood stabilate (S strain), whereas
      all control goats died. No attenuation of a second Cowdria stock (W) was achieved
      after 226 days in culture, at which time passage 17 was tested in a recipient
      goat which died of typical heartwater. This is the first report of vaccination
      with live attenuated C. ruminantium. These attenuated organisms may replace
      vaccination with virulent blood currently in use in areas where heartwater is
      endemic.

PMID- 1987090
TI  - Membrane skeleton protein 4.1 in inner segments of retinal cones.
AB  - Retinal cone photoreceptors are polarized cells with discrete functional
      compartments. Little is known of the membrane-skeleton components in cones
      responsible for the maintenance of cellular morphology and compartmentalization
      of integral membrane proteins. The authors describe a high density of the
      membrane-skeleton protein 4.1 in the myoid region of cones in retinas of
      developing and adult frogs, and adult lizards, turtles, and chicks. In the
      developing retina, a discrete locus of protein 4.1 is first detected by
      immunocytochemistry in the cone myoid after the completion of photoreceptor
      synaptogenesis. Protein 4.1 immunoreactivity expands to line the plasma membrane
      of the myoid after cones attain their adult proportions. Nonerythroid alpha
      spectrin and protein 4.1 colocalize in the cone myoid, and both are in close
      proximity to long bundles of f-actin that traverse the myoid and extend from the
      cone outer segment to the external limiting membrane. By analogy to the
      erythrocyte, where protein 4.1 modulates the interaction of spectrin and actin to
      regulate cell shape, the authors propose that protein 4.1 interacts with
      nonerythroid alpha-spectrin and f-actin in cones and plays a role in the
      maintenance of cone inner segment morphology.

PMID- 1987091
TI  - Resting voltage measurements of the rabbit corneal endothelium using patch
      current clamp techniques.
AB  - The resting potential (Em) of freshly isolated rabbit corneal endothelium was
      measured at room temperature (22 degrees C) and at 34 degrees C. Due to the wide
      range of values reported in the literature and the difficulty in obtaining long
      term measurements using microelectrodes in these cells, a current-clamp technique
      was employed using whole cell patch-clamp electrodes. The electrodes contained a
      K+ methanesulfonate-based intracellular solution, and a NaCl/HCO3- Ringer's
      solution was used extracellularly. Three preparations of endothelium were
      examined: single dissociated cells, the isolated monolayer (stripped from the
      stroma with Descemet's membrane), and the intact isolated cornea. The perforated
      patch technique, with amphotericin B in the electrode, was also used with the
      intact-cornea preparation at 34 degrees C. The mean Em values for the combined
      preparations at 22 degrees C and 34 degrees C were -35.3 mV and -55.0 mV,
      respectively; those for the intact-cornea preparation were -34.4 mV and -61.6 mV
      (at 22 degrees C and 34 degrees C, respectively). The isolated monolayer
      preparation showed a small but significant depolarization at both temperatures.
      These results demonstrate temperature dependence for Em in the corneal
      endothelium and show that more extensively dissected preparations have similar
      although not identical Ems to those of the intact cornea.

PMID- 1987092
TI  - Sprouting of corneal sensory fibers in rats treated at birth with capsaicin.
AB  - Normal structure and function of corneal epithelium is known to be related to
      proper innervation. To investigate possible trophic actions of sensory neurons on
      corneal epithelium, corneal innervation and various physical parameters were
      studied in normal rats and in rats treated as neonates with intraperitoneal
      injections of capsaicin. Corneal lesions were noted in treated rats which varied
      from multiple punctate areas of corneal opacity to deep stromal opacity with
      ulceration and neovascularization. These lesions waxed and waned throughout the
      animal's life. In addition, mechanical threshold of the corneal reflex was higher
      in capsaicin-treated rats. The tear rate in response to a provocative test was
      diminished in treated rats, presumably due to reduced afferent trigeminal input
      to the brain stem; blinking rates were more frequent in these animals. Using
      fluorescent retrograde tracing techniques, the number of cells innervating the
      cornea in capsaicin-treated rats was found to be significantly less compared with
      control animals. Innervation in the cornea (examined using a gold chloride
      technique) demonstrated a decrease in the number of corneal large axons in
      treated rats with neurite sprouting of these axons yielding a higher density of
      nerve fibers compared with controls. Thus, sprouting of residual sensory neurons
      occurs in response to the partial corneal denervation produced by capsaicin, and
      this sprouting does not functionally compensate to prevent the development of
      chronic keratitis.

PMID- 1987093
TI  - The pupillary effects of retrobulbar injection of botulinum toxin A (oculinum) in
      albino rats.
AB  - Botulinum toxin (BoTx) has been clinically used in the treatment of localized
      dystonic states such as blepharospasm, as well as in strabismus. Reported side
      effects have included primary excessive weakness of neighboring extraocular
      muscles. To evaluate possible involvement of the iris, we injected BoTx into the
      retrobular space of albino rats. Ipsilateral mydriasis with cholinomimetic
      supersensitivity developed in the treated animals. There was no apparent optic
      nerve dysfunction. The authors observed these effects using BoTx doses
      insufficient to cause clinical weakness or electrophysiological evidence of
      generalized neuromuscular dysfunction. The mydriasis disappeared spontaneously
      within 2-3 weeks. Higher BoTx doses resulted in severe neuromuscular paralysis
      and death. These findings were consistent with clinical botulism, which may
      include autonomic paralysis. The site of BoTx action could be the ciliary
      ganglion or cholinergic terminals in the iris. The authors concluded that side
      effects of BoTx were not necessarily limited to striated muscle weakness.

PMID- 1987094
TI  - Visual-evoked response binocular summation in normal and strabismic infants.
      Defining the critical period.
AB  - Pattern visual-evoked response binocular summation (VERBS) was recorded in normal
      infants, between the ages of 1-58 months, and in similar-aged esotropic infants
      before and at various times after corrective surgery. The normal subjects had no
      significant VERBS at 1.5 months of age, developed a rapid acceleration of VERBS
      between 1.5-3 months, and then gradually declined in VERBS from 3-58 months. The
      peak of the VERBS by age function at 3 months was well in the facilitation range
      (greater than 2.0) and corresponded to the general age range for the onset of
      binocular eye alignment, fusion, and stereopsis. The results from the early-onset
      esotropic patients revealed a similar function to that found in normal subjects;
      however, the function was triggered by surgical eye alignment. The peak of the
      VERBS function for esotropic subjects was lower than normal, and the initial rise
      was less rapid. It is proposed that the VERBS function reflects the human
      critical period for the development of binocular vision. In this framework, data
      from both infant developmental studies and adult studies were clarified.

PMID- 1987095
TI  - Early visual deprivation results in persistent strabismus and nystagmus in
      monkeys.
AB  - To understand to what extent visual-pattern deprivation during infancy results in
      strabismus and nystagmus, the authors examined the long-term consequences of this
      type of deprivation in monkeys during the first 50 days of life. Three cynomolgus
      and three rhesus monkeys had the eyelids sutured closed within 24 hr of birth. At
      25 days of age, the eyelids were opened, and the eyelids of the fellow eye were
      sutured closed for an additional 25 days (reverse-eyelid suture). When the
      eyelids were opened at 50 days of age, each monkey was found to have 20-30 delta
      of exotropia and nystagmus, which persisted for the duration of the study (1 yr).
      The cynomolgus monkeys developed a monocular 8-10 Hz pendular nystagmus in the
      eye sutured first. The rhesus monkeys developed a conjugate nystagmus with both
      jerk and pendular components. The slow phases often had velocity-increasing
      profiles. The rhesus monkeys also had a superimposed latent component to the
      nystagmus found during monocular viewing. One additional rhesus monkey was
      examined after 55 days of binocular-eyelid suturing. This monkey also developed
      exotropia and nystagmus resembling that of the other rhesus monkeys. These
      findings suggest that early pattern vision in monkeys is necessary for the
      development of normal ocular alignment and gaze-holding ability.

PMID- 1987096
TI  - Effect of surround propinquity on the open-loop accommodative response.
AB  - The effect of knowledge of surround propinquity, ie, awareness of proximity of
      the adjacent surroundings, on the open-loop accommodative response (AR) was
      determined by comparing measurements of accommodation obtained in total darkness
      in two different-sized rooms. The AR was measured in two laboratories, one 2.5-m
      square and the other 6.75 x 2.75 m. Steady-state accommodation was assessed on
      two occasions in each room using an infrared optometer. On the first occasion,
      the subjects (n = 10) were fully aware of the laboratory dimensions and
      topography. For the second trial, they were blind-folded before entering the
      laboratory and hence were unaware of the experimental location. When subjects
      were unaware of the laboratory dimensions, no significant difference existed
      between the recorded values of AR. However, when subjects were initially able to
      observe the size of the room, the AR in darkness was significantly higher in the
      smaller laboratory. This suggests that proximally induced accommodation,
      initiated by prior knowledge of the dimensions of the laboratory, was responsible
      for this increase in AR. Furthermore, it is proposed that complex interactions
      exist between proximal, tonic, and other nonoptical accommodative stimuli such
      that it may be impossible to isolate an individual, nonoptical accommodative
      component.

PMID- 1987097
TI  - Accommodative hysteresis. Fundamental asymmetry in decay rate after near and far
      focusing.
AB  - The resting level of accommodation, or dark focus (DF), was compared before and
      after subjects maintained 8-min of clear focus on targets either at the far point
      (FP) of accommodation or at an equivalent dioptric distance on the near side of
      the DF. Although both conditions showed significant shifts in tonic accommodation
      in the direction of their respective fixation targets, only after near fixation
      was the shift maintained in darkness for 24-min postfixation. After FP viewing
      the aftereffect decayed in darkness with a significant linear trend (P less than
      0.05). Thus, maintaining focus on a near target is more likely to induce an
      enduring adaptive shift in tonic accommodation than is far-target viewing, for
      reasons associated with the systems controlling far and near accommodation,
      respectively. Additional analyses provided further evidence that the degree of
      separation of the target from the DF is a highly significant factor controlling
      individual differences in initial adaptation levels.

PMID- 1987098
TI  - Extraocular muscle regeneration in freeze-treated extraocular muscle autografts.
AB  - New growth of extraocular muscle has been demonstrated in degenerating peripheral
      nerve autografts implanted between two extraocular muscles. This suggests that
      extraocular muscle may be lengthened for therapeutic purposes if a suitable
      matrix can be found to support this new growth. Investigators of peripheral nerve
      regeneration have found that the basal lamina of freeze-killed skeletal muscle
      remains intact and supports axonal regeneration. This study was designed to
      investigate the feasibility of inducing regenerative growth of extraocular muscle
      in freeze-treated extraocular muscle autografts. In six beagles the inferior
      oblique muscle was removed from both orbits, frozen in liquid nitrogen, and
      allowed to thaw at room temperature. The freeze-thaw cycle was repeated. The
      freeze-treated grafts were then sewn in an end-to-end fashion between the cut end
      of the lateral rectus and the globe. At both 4 and 8 weeks postoperatively, three
      dogs were killed, and the grafts were removed from both orbits. These were
      prepared for light and electron microscopic examination. This revealed robust
      growth of mature-appearing, innervated muscle fibers in the proximal graft that
      could be differentiated by adenosine triphosphatase histochemistry. Rare,
      immature fibers were seen in the distal graft. These results demonstrate that
      freeze-treated extraocular muscle autografts support regenerative growth of
      extraocular muscle.

PMID- 1987099
TI  - Morphology of the trabecular meshwork and inner-wall endothelium after cationized
      ferritin perfusion in the monkey eye.
AB  - Nine eyes of five cynomolgus monkeys were perfused through the anterior chamber
      with cationized ferritin (CF) at normal and increased intraocular pressure. After
      perfusion with glutaraldehyde, the morphologic appearance of the endothelial
      lining of Schlemm's canal (SC) and of the adjacent regions was analyzed using
      tangential and sagittal serial sections. The CF, which binds to negatively
      charged surfaces, was observed to be adherent to the free surfaces of trabecular
      cell membranes and to accumulate in the cribriform layer underlining the
      endothelial lining of SC. Tangential sections of the inner-wall endothelium
      demonstrated that separations of the adjacent cell membranes occur between the
      tight junctions forming openings or lacunae and bent, tunnel-like channels that
      represent continuous paracellular pathways. Complete staining of these inner-wall
      paracellular pathways with CF were observed indicating that the adjoining
      membranes are negatively charged and that the perfused fluid had passed through
      these intercellular channels. These paracellular pathways appeared enlarged and
      were more easily identified at elevated perfusion pressure. In general,
      intracytoplasmic vacuoles demonstrated heavy staining with CF on their luminal
      surface but only faint staining on the adluminal (cribriform-facing) surface.
      Apparent giant vacuoles were observed to be often not real intracellular vacuoles
      but rather dilatations of the paracellular spaces. This study demonstrates that
      there are paracellular routes through the inner-wall endothelium by which high
      molecular-weight substances such as ferritin and macrophages can leave the
      anterior chamber. Probably there are both transcytoplasmic and paracellular
      mechanisms of aqueous outflow that may vary under different conditions of
      pressure or flow.

PMID- 1987100
TI  - Lenses of diabetic patients "yellow" at an accelerated rate similar to older
      normals.
AB  - The authors used a psychophysical method to measure lens transmission of young,
      type I diabetic patients and normal controls. The results from normal controls
      agreed with previously published reports of decreasing lens transmission with
      age, and those from diabetic subjects suggested that lenses of young, type I
      diabetic patients age or "yellow" at an accelerated rate that was similar to that
      of normal controls over the age of 60 yr. The rate of accelerated lens density
      that occurs per year with the duration of diabetes is similar to the rate of
      accelerated lens density that occurs per year with patient age over 60 yr. A
      possible molecular explanation for the accelerated lens yellowing in both
      populations is discussed. Both diabetic individuals and the older normal
      populations have elevated plasma glucose levels and therefore may have
      accelerated glycosylation of lens proteins which causes increased lens yellowing.

PMID- 1987101
TI  - Numbers of cortical vitreous cells and onset of cataracts in Royal College of
      surgeons rats.
AB  - Royal College of Surgeons (RCS) rats have hereditary retinal degeneration with
      associated posterior subcapsular opacities. A link between light, retinal
      degeneration, and cataracts may consist in peroxidation of polyunsaturated fatty
      acids of rod outer segment lipids to yield water-soluble toxic aldehydes that can
      traverse the vitreous and react with bow cells and posterior lens fibers. In an
      immune reaction to the retinal degeneration, macrophages multiply in the retina
      and in the cortex of the vitreous. In dystrophics, the cortical vitreous
      separates readily from attachments to retina, ciliary body and lens, and from the
      vitreous gel. This web-like structure was stained and spread on a counting
      chamber. Cells were counted at 15-130 postnatal days in pink- and black-eyed RCS
      dystrophics and in congenic controls to correlate numbers of cells, temporal and
      geographic patterns of retinal degeneration, and onset of opacities. Rats were
      reared in cyclic light (10-40 lux inside the cage) and fed a natural ingredient
      diet (NIH-07). Cortical vitreous cells increased markedly in pink- and black-eyed
      dystrophics at 50-53 days when slit-lamp detectable opacities occurred in both.
      The increase was 4.6-fold in pink- and 2.3-fold in black-eyed rats compared with
      controls. At 50-53 days, the dystrophy affected all quadrants of the retina
      severely in pink-eyed RCS but only the inferior periphery in black-eyed RCS.
      Consequently, severe degeneration in one quadrant may suffice to initiate an
      opacity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1987102
TI  - Angiotensin II binding receptors in retinal and optic nerve head blood vessels.
      An autoradiographic approach.
AB  - Angiotensin II (AII) binding sites were identified in cross-sections of the cat
      retinal and optic nerve vasculatures. The authors used 3H-AII and 125I-saralasin,
      an agonist and a high-affinity antagonist of AII receptors, respectively, to
      generate light microscopy autoradiograms in resin-embedded tissues. With both
      radioligands the presence of AII binding sites was confirmed in retinal
      arterioles but not in the veins or capillaries of the retina. Additionally the
      presence of such binding sites in the capillaries of the optic nerve head was
      shown. These results support the hypothesis that microvascular tone and perhaps
      autoregulatory responses of optic nerve capillaries might be influenced by
      vasoactive substances, such as AII, either leaking from the choroid or locally
      synthetized.

PMID- 1987103
TI  - Immune privilege extended to allogeneic tumor cells in the vitreous cavity.
AB  - Inoculation of alloantigenic P815 tumor cells into the vitreous cavity of eyes of
      BALB/c mice resulted in the intraocular development of progressively growing
      tumors. We observed by clinical and histologic examination that the tumors
      acquired a blood supply, lacked significant necrosis or degeneration, and
      gradually penetrated the globe into the orbit. Mice bearing these intraocular
      tumors did not develop tumor-specific delayed hypersensitivity (DH), and their
      spleens contained lymphocytes capable of suppressing tumor-specific DH when
      transferred adoptively into naive, syngeneic recipients. The authors conclude
      that the vitreous cavity (VC) is an immunologically privileged site for
      histoincompatible tumor cells and that the privilege is mediated by active
      suppression of DH, similar to anterior chamber (AC)-associated, immune deviation.

PMID- 1987104
TI  - Endothelin-1-induced contraction of bovine retinal small arteries is reversible
      and abolished by nitrendipine.
AB  - Endothelin-1 (porcine/human) induced a prompt, reversible, potent, concentration
      dependent contraction of bovine isolated retinal small arteries (internal
      diameter, approximately 200 microns) with a concentration of endothelin-1
      required to give half-maximal contraction of 2 x 10(-10) M. The maximal
      contraction induced by endothelin-1 was equal to 89% of the maximal contractile
      capacity. The vessel response to endothelin-1 was dependent on extracellular
      Ca2+. Withdrawal of extracellular Ca2+ or addition of nitrendipine, 10(-6) M,
      reduced the response of vessels contracted with 10(-9) M endothelin-1 by 80% and
      75%, respectively. These results indicate that the endothelin-1-induced
      contraction of retinal arteries is dependent on an influx of extracellular Ca2+
      through membrane potential-operated calcium channels. Endothelin-1, 10(-13)-10(
      10) M, did not induce a relaxation of endothelium-intact arteries, indicating
      that endothelin-1 is incapable of releasing endothelium-derived relaxing factor
      in the retinal circulation. These results suggest that endothelin may participate
      in the regulation of retinal artery tone.

PMID- 1987105
TI  - Effect of two weeks of timolol maleate treatment on the normal retinal
      circulation.
AB  - The effect of 2 weeks of topical treatment with timolol maleate 0.5% ophthalmic
      solution on the retinal circulation was investigated using bidirectional laser
      Doppler velocimetry and monochromatic fundus photography. Fifteen normal healthy
      volunteers were included in this study. In a double-masked, randomized design one
      eye of each received one drop of timolol maleate 0.5% twice daily for 14 days,
      and the fellow eye received placebo. Vessel diameter (D), maximum erythrocyte
      velocity (Vmax), and volumetric blood flow rate (Q) were determined in one major
      retinal vein of each eye before treatment, and then, 2 hr after the instillation
      of drops on the morning of the 15th day of treatment. After treatment, the
      average change from baseline in D (+0.7%), Vmax (-8.2%) and Q (-7.7%) were not
      statistically significant in the placebo-treated eyes. In the timolol-treated
      eyes, the average increase from baseline in D (+0.1%) and Q (+10%) were not
      statistically significant. Average Vmax, on the other hand, increased
      significantly from baseline (P less than 0.05) by 9.6%. In comparison to the
      placebo-treated eyes, Vmax and Q were significantly increased in the timolol
      treated eyes (P less than 0.0005 and P less than 0.01, respectively). These
      results are similar to those reported previously in a study of the effect of a
      one-time instillation of timolol and, therefore, suggest that the effect of
      timolol on the retinal circulation is maintained over a 2-week period.

PMID- 1987106
TI  - An experimental model of preretinal neovascularization in the rabbit.
AB  - Although progressive retinal neovascularization is a potentially blinding
      complication of several diseases, there are no good animal models. The authors
      developed a consistent model of preretinal neovascularization in the rabbit by
      partially digesting the posterior vitreous with repeated injection and aspiration
      of 1 IU of hyaluronidase before injection of 250,000 homologous dermal
      fibroblasts. The evolution of the new preretinal vessels was monitored by
      indirect ophthalmoscopy, fundus photography, and fluorescein angiography. A
      grading system was devised using fundus photographs and fluorescein angiograms to
      describe the progression of new vessel growth and the extent of fluorescein
      leakage. Ninety-five percent of the eyes had vascular enlargement and hyperemia
      but no fluorescein leakage by day 1. Fifteen percent of the eyes had clinically
      evident new preretinal vessels, and 32% had severe fluorescein leakage by day 7.
      Ninety-five percent of the eyes had definite neovascularization by day 14. Severe
      fluorescein leakage peaked at day 14 (55% of the eyes) and decreased thereafter.
      Involution or atrophy of the vessels occurred in all eyes by day 42. This model
      will be useful for studying the pathogenesis of preretinal neovascularization and
      evaluating potential treatments for its prevention.

PMID- 1987107
TI  - Recovery of retinal pigment epithelial function after ischemia in the rabbit.
AB  - Survival of the rabbit retinal pigment epithelium (RPE) after ischemia was
      studied. The ischemia was induced by elevating intraocular pressure; retinal and
      RPE function were monitored by electrophysiologic recordings. The b-wave
      recovered to control amplitude in 1-4 hr after 30-60 min of ischemia, but it
      never recovered more than about 50% amplitude after 90 min of ischemia. The c
      wave recovered after 30 min of ischemia but was replaced by a negative response
      after 60-90 min of ischemia. The RPE hyperosmolarity response was normal after 60
      min of ischemia, but it was severely depressed after 90 min of ischemia. The RPE
      response to acetazolamide (cornea positive in the rabbit) was lost after both 60
      and 90 min of ischemia. These results suggest that different components of RPE
      function have different tolerances to ischemia and is consistent with evidence
      that the RPE electrophysiologic responses differ in mechanism and response to
      disease.

PMID- 1987108
TI  - Relations between fundus appearance and function. Eyes whose fellow eye has
      exudative age-related macular degeneration.
AB  - Foveal visual function was compared with fundus appearance for 41 eyes that had
      good acuity but whose fellow eye had exudative age-related macular degeneration
      (AMD). The visual functions tested were among those reported to be compromised by
      AMD. They included: (1) dark adaptation, (2) absolute sensitivity, (3) S cone
      mediated sensitivity, and (4) color matching. The fundus features used to
      evaluate the risk of developing exudative AMD included: (1) drusen confluence,
      (2) drusen size, and (3) focal hyperpigmentation. For the group of eyes defined
      by the presence of one or more high-risk fundus characteristics, all visual
      functions were compromised significantly. In particular, all 21 eyes with
      abnormally slow rates of dark adaptation had high-risk fundi, and all 16 eyes
      with abnormal color matching (ie, a small effect of test area on the color match
      or rejection of all potential color matches) had high-risk fundi. Conversely, 30
      of the 32 eyes with high-risk fundi had abnormally slow rates of dark adaptation
      or abnormal color matching. In addition, reduced acuity in the fellow exudative
      eye was associated significantly with a high-risk fundus in the nonexudative eye.

PMID- 1987109
TI  - Analysis of interleukin-6 in endotoxin-induced uveitis.
AB  - The mechanisms underlying the induction of intraocular inflammation in the rat
      model of endotoxin-induced uveitis (EIU) and the subsequent development of
      tolerance after repeated endotoxin injections are poorly understood. Interleukin
      6 (IL-6) was measured in the aqueous humor and serum of Lewis rats after single
      and repeated injections of endotoxin into the footpad. After a single injection,
      a rise in serum and aqueous-humor levels of IL-6 was seen after 2 and 16 hr,
      respectively. The highest aqueous-humor level of IL-6 was seen 20 hr
      postinjection and was tenfold that seen in the serum sample taken at the same
      time, suggesting intraocular synthesis of this cytokine. Four hours later the
      most active uveitis and the highest total aqueous-humor protein level were
      observed. Repeated injection of endotoxin still resulted in a moderate but
      significant systemic release of IL-6 but no detectable IL-6 in the aqueous humor
      and the absence of uveitis. Intravitreal injection of endotoxin-free human
      recombinant IL-6 (10-10(5) U) in rats resulted in uveitis, resembling the ocular
      response to endotoxin. There appeared to be a prozone effect regarding the total
      aqueous-humor protein concentration. The largest amount of aqueous-humor protein
      was seen in the eyes injected with 10(2) U of IL-6, but increasing concentrations
      of intravitreal IL-6 showed a corresponding decrease in protein levels. In the
      fellow saline-injected eyes, a clear consensual response was observed with regard
      to the extravasation of protein, although the uveitic grade in these eyes was low
      or zero. Repeated intravitreal injection of IL-6 resulted in ocular
      unresponsiveness in nine of 11 rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1987110
TI  - Cell cycle-independent lysis of Escherichia coli by cefsulodin, an inhibitor of
      penicillin-binding proteins 1a and 1b.
AB  - Cefsulodin lyses actively growing Escherichia coli by binding specifically to
      penicillin-binding proteins (PBPs) 1a and 1b. Recent findings (F. Garcia del
      Portillo, M. A. de Pedro, D. Joseleau-Petit, and R. D'Ari, J. Bacteriol. 171:4217
      4221, 1989) have linked cefsulodin-induced lysis to septation during the first
      division cycle after a nutritional shift-up or chromosome replication
      realignment. We synchronized cells by membrane filtration to determine whether
      cefsulodin-induced lysis depended on septation in normally growing cells.
      Populations of newly divided cells were allowed to grow for variable lengths of
      time. Cefsulodin was added to these synchronous cultures, which represented
      points in two to three rounds of the cell cycle. Since the cell numbers were
      small, a new lysis assay was developed that was based on the release of DNA
      measured by fluorometry. Lysis occurred at a constant time after addition of the
      antibiotic, regardless of the time in the cell cycle at which the addition was
      made. Thus, cefsulodin-induced lysis is not linked to septation or to any other
      cell cycle-related event.

PMID- 1987111
TI  - Nucleotide sequence of the glpD gene encoding aerobic sn-glycerol 3-phosphate
      dehydrogenase of Escherichia coli K-12.
AB  - Aerobic sn-glycerol 3-phosphate dehydrogenase, encoded by the glpD gene of
      Escherichia coli, is a cytoplasmic membrane-associated respiratory enzyme. The
      nucleotide sequence of glpD was determined. An open reading frame of 501 codons
      was preceded by a consensus Shine-Dalgarno sequence. The proposed translational
      start and reading frame of glpD were confirmed by determining the nucleotide
      sequence across the fusion joint of a glpD-lacZ translational fusion. The
      predicted molecular weight, 56,750, corresponds well with the reported value of
      58,000 for purified sn-glycerol 3-phosphate dehydrogenase. The flavin-binding
      domain, located at the amino terminus, was identified by comparison with the
      amino acid sequences of other flavoproteins from E. coli. Repetitive extragenic
      palindromic sequences were identified downstream of the glpD coding region. The
      site for transcription termination was located between 87 and 216 bp downstream
      of the translation stop codon.

PMID- 1987112
TI  - Cloning, nucleotide sequence, and characterization of mtr, the structural gene
      for a tryptophan-specific permease of Escherichia coli K-12.
AB  - The mtr gene of Escherichia coli K-12 encodes an L-tryptophan-specific permease.
      This gene was originally identified through the isolation of mutations in the 69
      min region of the chromosome, closely linked to argG. Cells with lesions in mtr
      display a phenotype of 5-methyltryptophan resistance. The mtr gene was cloned by
      using the mini-Mu system. The amino acid sequence of Mtr (414 codons), deduced by
      DNA sequence analysis, was found to be 33% identical to that of another single
      component transport protein, the tyrosine-specific permease, TyrP. The hydropathy
      plots of the two permeases were similar. Possible operator sites for the tyrosine
      and tryptophan repressors are situated within the region of DNA that is likely to
      be the mtr promoter.

PMID- 1987113
TI  - Lanthanide accumulation in the periplasmic space of Escherichia coli B.
AB  - Treatment of growing Escherichia coli B with lanthanide ions [lanthanum(III),
      terbium(III), and europium(III)] and subsequent aldehyde-OsO4 fixation caused
      areas of high contrast to appear within the periplasm (the space between inner
      and outer membrane of the cell envelope). X-ray microanalysis of ultrathin
      sections of Epon-embedded or acrylic resin-embedded cells revealed the presence
      of the lanthanide and of phosphorus in the areas, whose contrast greatly exceeded
      that of other stained structures. Comparatively small amounts of the lanthanide
      were also present in the outer membrane and in the cytoplasm. The distribution of
      the periplasmic areas of high contrast was found to be random and not clustered
      at areas of current or future septum formation. Irregular cell shapes were
      observed after lanthanide treatment before onset of fixation. In contrast to
      glutaraldehyde-OsO4 fixation, glutaraldehyde used as the sole fixer caused a
      scattered distribution of the lanthanide. Cryofixation (slam-freezing) and freeze
      substitution revealed a lanthanum stain at both the periplasm and the outer part
      of the outer membrane. Deenergization of the cell membrane by either phage T4 or
      carbonyl cyanide m-chlorophenylhydrazone abolished the metal accumulation.
      Furthermore, addition of excess calcium, administered together with the
      lanthanide solution, diminished the quantity and size of areas of high contrast.
      Cells grown in media of high NaCl concentration revealed strongly stained areas
      of periplasmic precipitates, whereas cells grown under low-salt conditions showed
      very few high-contrast patches in the periplasm. Terbium treatment (during
      fixation) enhanced the visibility of the sites of inner-outer membrane contact
      (the membrane adhesion sites) in plasmolized cells, possibly as the result of an
      accumulation of the metal at the adhesion domains. The data suggest a rapid
      interaction of the lanthanides with components of the cell envelope, the
      periplasm, and the energized inner membrane.

PMID- 1987114
TI  - Isolation of temperature-sensitive McrA and McrB mutations and complementation
      analysis of the McrBC region of Escherichia coli K-12.
AB  - We isolated temperature-sensitive mcrA and mcrBC mutants of Escherichia coli. At
      42 degrees C, they were unable to restrict the T-even bacteriophages T6gt and
      T4gt or plasmids encoding cloned DNA methylase genes whose specificities confer
      sensitivity to the McrA and McrBC nucleases. Complementation analysis of the
      McrBC region (mcrB251) with the complete cloned McrBC system or a derivative with
      mcrB alone indicated that the mutation shows an absolute defect for the
      restriction of DNA containing hydroxymethylcytosine and a thermosensitive defect
      for the restriction of DNA containing methylcytosine. The properties of the McrA
      temperature-sensitive mutants suggest that some of these mutations can also
      influence the restriction of DNA containing hydroxymethylcytosine or
      methylcytosine residues.

PMID- 1987115
TI  - Molecular characterization of an Enterobacter cloacae outer membrane protein
      (OmpX).
AB  - A chromosomal gene of Enterobacter cloacae encoding an outer membrane protein
      (OmpX) has been cloned. Overproduction of the OmpX protein decreased the quantity
      of porins in the outer membrane of the parental strain and of Escherichia coli
      HB101. The ompX gene was located by insertions of the gamma delta sequence into
      the recombinant plasmid. The polarity of the gene was determined by in vitro
      transcription and translation of the gamma delta-containing plasmids. The
      nucleotide sequence of the ompX gene was elucidated by using both inverted
      terminal repeats of the gamma delta sequence as starting points for M13 dideoxy
      sequencing. The gene was found to encode a precursor of the OmpX protein
      consisting of 172 amino acid residues with a molecular mass of 18.6 kDa. The
      protein contains an N-terminal signal sequence of 23 amino acid residues. The
      exact cleavage point was established by sequencing the N-terminal part of the
      mature protein. The OmpX protein has several characteristics in common with outer
      membrane proteins of gram-negative bacteria. The protein is rather hydrophilic
      and is devoid of long hydrophobic stretches. On the basis of these results, we
      present a model for the OmpX protein folding in an outer membrane.

PMID- 1987116
TI  - Molecular analysis of the Alcaligenes eutrophus poly(3-hydroxybutyrate)
      biosynthetic operon: identification of the N terminus of poly(3-hydroxybutyrate)
      synthase and identification of the promoter.
AB  - Molecular methods have been applied to analyze the expression of the Alcaligenes
      eutrophus poly(3-hydroxybutyrate) (PHB) synthase gene (phbC). The translational
      initiation codon was identified by analysis of the amino acid sequence of a PHB
      synthase-beta-galactosidase fusion protein. This protein was purified to almost
      gel electrophoretic homogeneity by chromatography on DEAE-Sephacel and on
      aminophenyl-beta-D-thiogalactopyranoside-Sepharose from cells of A. eutrophus
      which harbored a phbC'-'lacZ fusion gene. A sequence (TTGACA-18N-AACAAT),
      exhibiting striking homology to the Escherichia coli sigma 70 promoter consensus
      sequence, was identified approximately 310 bp 5' upstream from the translation
      initiation codon. An S1 nuclease protection assay mapped the transcription start
      point of phbC 6 bp downstream from this promoter. The location of the promoter
      was confirmed by analyzing the expression of active PHB synthase in clones of E.
      coli harboring 5' upstream deletions of phbC ligated to the promoter of the lacZ
      gene (lacZp) in a Bluescript vector. Plasmids do181 and do218, which were deleted
      for the first 108 or 300 bp of the phbC structural gene, respectively, conferred
      the ability to synthesize large amounts of different truncated PHB synthase
      proteins to the cells. These proteins contributed to approximately 10% of the
      total cellular protein as estimated from sodium dodecyl sulfate-polyacrylamide
      gels. The modified PHB synthase encoded by plasmid do181 was still active. Clones
      in which the lacZp-'phbC fusion harbored the complete phbC structural gene plus
      the phbC ribosome binding site did not overexpress PHB synthase.

PMID- 1987117
TI  - Synthesis and functioning of the colicin E1 lysis protein: comparison with the
      colicin A lysis protein.
AB  - The colicin E1 lysis protein, CelA, was identified as a 3-kDa protein in induced
      cells of Escherichia coli K-12 carrying pColE1 by pulse-chase labeling with
      either [35S]cysteine or [3H]lysine. This 3-kDa protein was acylated, as shown by
      [2-3H]glycerol labeling, and seemed to correspond to the mature CelA protein. The
      rate of modification and processing of CelA was different from that observed for
      Cal, the colicin A lysis protein. In contrast to Cal, no intermediate form was
      detected for CelA, no signal peptide accumulated, and no modified precursor form
      was observed after globomycin treatment. Thus, the rate of synthesis would not be
      specific to lysis proteins. Solubilization in sodium dodecyl sulfate of the
      mature forms of both CelA and Cal varied similarly at the time of colicin
      release, indicating a change in lysis protein structure. This particular property
      would play a role in the mechanism of colicin export. The accumulation of the
      signal peptide seems to be a factor determining the toxicity of the lysis
      proteins since CelA provoked less cell damage than Cal. Quasi-lysis and killing
      due to CelA were higher in degP mutants than in wild-type cells. They were
      minimal in pldA mutants.

PMID- 1987118
TI  - Regulation of proline utilization in Salmonella typhimurium: a membrane
      associated dehydrogenase binds DNA in vitro.
AB  - The PutA protein is a membrane-associated enzyme that catalyzes the degradation
      of proline to glutamate. Genetic evidence suggests that in the absence of
      proline, the PutA protein also represses transcription of the putA and putP
      genes. To directly determine whether PutA protein binds to the put control
      region, we analyzed gel retardation of put control region DNA by purified PutA
      protein in vitro. The put control region is 420 bp. Purified PutA protein bound
      specifically to several nonoverlapping fragments of control region DNA,
      indicating the presence of multiple binding sites in the control region.
      Electrophoretic abnormalities and behavior of circularly permuted fragments of
      control region DNA indicate that it contains a region of intrinsically curved
      DNA. To determine whether the multiple binding sites or the DNA curvature are
      important in vivo, two types of deletions were constructed: (i) deletions that
      removed sequences predicted to contribute to DNA curvature as well as potential
      operator sites and (ii) deletions that removed only potential operator sites.
      Both types of deletions increased expression of the put genes but were still
      induced by proline, indicating that multiple cis elements are involved in
      repression. These data suggest a model for put repression that invokes the
      formation of a complex between PutA protein molecules bound at different sites in
      the control region, brought into proximity by a loop of curved DNA.

PMID- 1987119
TI  - Detergent (sodium dodecyl sulfate) shock proteins in Escherichia coli.
AB  - The protein composition of Escherichia coli W3110 grown in the presence and
      absence of 5% sodium dodecyl sulfate (SDS) was examined by two-dimensional gel
      electrophoresis. In SDS-grown cells, at least 4 proteins were turned on, 13 were
      turned off, 15 were elevated, and 15 were depressed. The 19 unique and elevated
      SDS-induced spots constituted 7.91% of the total 35S-labeled protein. There was
      no apparent overlap between these 19 detergent (SDS) stress proteins and those of
      other known bacterial stress responses. The detergent stress stimulon is a
      distinct and independent stimulon. Its physiological relevance probably derives
      from the presence of bile salts in animal gastrointestinal tracts.

PMID- 1987120
TI  - Role of uracil-DNA glycosylase in mutation avoidance by Streptococcus pneumoniae.
AB  - Uracil-DNA glycosylase activity was found in Streptococcus pneumoniae, and the
      enzyme was partially purified. An ung mutant lacking the activity was obtained by
      positive selection of cells transformed with a plasmid containing uracil in its
      DNA. The effects of the ung mutation on mutagenic processes in S. pneumoniae were
      examined. The sequence of several malM mutations revertible by nitrous acid
      showed them to correspond to A.T----G.C transitions. This confirmed a prior
      deduction that nitrous acid action on transforming DNA gave only G.C----A.T
      mutations. Examination of malM mutant reversion frequencies in ung strains
      indicated that G.C----A.T mutation rates generally were 10-fold higher than in
      wild-type strains, presumably owing to lack of repair of deaminated cytosine
      residues in DNA. No effect of ung on mutation avoidance by the Hex mismatch
      repair system was observed, which means that uracil incorporation and removal
      from nascent DNA cannot be solely responsible for producing strand breaks that
      target nascent DNA for correction after replication. One malM mutation
      corresponding to an A.T----G.C transition showed a 10-fold-higher spontaneous
      reversion frequency than other such transitions in a wild-type background. This
      "hot spot" was located in a directly repeated DNA sequence; it is proposed that
      transient slippage to the wild-type repeat during replication accounts for the
      higher reversion frequency.

PMID- 1987121
TI  - Sequence domains required for the activity of avirulence genes avrB and avrC from
      Pseudomonas syringae pv. glycinea.
AB  - avrB and avrC from Pseudomonas syringae pv. glycinea share significant amino acid
      homology but interact with different soybean resistance genes to elicit the
      hypersensitive defense reaction. Recombinant genes constructed between avrB and
      avrC revealed that the central regions were required for avirulence gene activity
      but the 5' and 3' termini were interchangeable. Recombinants involving the
      central regions did not yield any detectable avirulence gene activity, and no new
      avirulence phenotypes were observed from any of the chimeric genes. These results
      suggest that the protein products of avrB and avrC possess catalytic properties
      that are required for the avirulence phenotypes.

PMID- 1987122
TI  - Unusual sequence organization in CenB, an inverting endoglucanase from
      Cellulomonas fimi.
AB  - The nucleotide sequence of the cenB gene was determined and used to deduce the
      amino acid sequence of endoglucanase B (CenB) of Cellulomonas fimi. CenB
      comprises 1,012 amino acids and has a molecular weight of 105,905. The
      polypeptide is divided by so-called linker sequences rich in proline and
      hydroxyamino acids into five domains: a catalytic domain of 607 amino acids at
      the N terminus, followed by three repeats of 98 amino acids each which are
      greater than 60% identical, and a C-terminal domain of 101 amino acids which is
      50% identical to the cellulose-binding domains of C. fimi cellulases Cex and
      CenA. A deletion mutant of the cenB gene encodes a polypeptide lacking the C
      terminal 333 amino acids of CenB. The truncated polypeptide is catalytically
      active and, like intact CenB, binds to cellulose, suggesting that CenB has a
      second cellulose-binding site. The sequence of amino acids 1 to 461 of CenB is
      35% identical, with a further 15% similarity, to that of a cellulase from
      avocado, which places CenB in cellulase family E. CenB releases mostly cellobiose
      and cellotetraose from cellohexaose. Like CenA, CenB hydrolyzes the beta-1,4
      glucosidic bond with inversion of the anomeric configuration. The pH optimum for
      CenB is 8.5, and that for CenA is 7.5.

PMID- 1987123
TI  - High-level expression of Escherichia coli NADPH-sulfite reductase: requirement
      for a cloned cysG plasmid to overcome limiting siroheme cofactor.
AB  - The flavoprotein and hemoprotein components of Escherichia coli B NADPH-sulfite
      reductase are encoded by cysJ and cysI, respectively. Plasmids containing these
      two genes overexpressed flavoprotein catalytic activity and apohemoprotein by 13-
      to 35-fold, but NADPH-sulfite reductase holoenzyme activity was increased only 3
      fold. Maximum overexpression of holoenzyme activity was achieved by the inclusion
      in such plasmids of Salmonella typhimurium cysG, which encodes a uroporphyrinogen
      III methyltransferase required for the synthesis of siroheme, a cofactor for the
      hemoprotein. Thus, cofactor deficiency, in this case siroheme, can limit
      overexpression of a cloned enzyme. Catalytically active holoenzyme accounted for
      10% of total soluble protein in a host containing cloned cysJ, cysI, and cysG. A
      5.3-kb DNA fragment containing S. typhimurium cysG was sequenced, and the open
      reading frame corresponding to cysG was identified by subcloning and by
      identifying plasmid-encoded peptides in maxicells. Comparison with the sequence
      reported for the E. coli cysG region (J. A. Cole, unpublished data; GenBank
      sequence ECONIRBC) indicates a gene order of nirB-nirC-cysG in the cloned S.
      typhimurium fragment. In addition, two open reading frames of unknown identity
      were found immediately downstream of cysG. One of these contains 11 direct
      repeats of 33 nucleotides each, which correspond to the consensus amino acid
      sequence Asp-Asp-Val-Thr-Pro-Pro-Asp-Asp-Ser-Gly-Asp.

PMID- 1987124
TI  - Cloning and nucleotide sequence of the firA gene and the firA200(Ts) allele from
      Escherichia coli.
AB  - The Escherichia coli gene firA, previously reported to code for a small,
      histonelike DNA-binding protein, has been cloned and found to reside immediately
      downstream from skp, a gene previously identified as the firA locus. firA encodes
      a 36-kDa protein. The mutant firA200(Ts) allele was also cloned and shown to
      contain three mutations, each mutation giving rise to a single amino acid change.
      Partially purified wild-type FirA (from a firA+ strain) and mutant FirA [from a
      firA200(Ts) strain] proteins have amino-terminal sequences predicted from their
      common DNA sequences. Both proteins lack an N-terminal methionine. Modest
      overexpression of wild-type or mutant FirA restored wild-type growth to
      firA200(Ts) strains at 43 degrees C, whereas high-level expression of wild-type
      FirA was required for more complete suppression of the rifampin sensitivity of
      firA200(Ts) rpoB double mutants. High-level expression of mutant FirA did not
      suppress this rifampin sensitivity.

PMID- 1987125
TI  - Degradation of 2,4-dichlorophenol by the lignin-degrading fungus Phanerochaete
      chrysosporium.
AB  - Under secondary metabolic conditions the white rot basidiomycete Phanerochaete
      chrysosporium mineralizes 2,4-dichlorophenol (I). The pathway for the degradation
      of 2,4-dichlorophenol (I) was elucidated by the characterization of fungal
      metabolites and of oxidation products generated by purified lignin peroxidase and
      manganese peroxidase. The multistep pathway involves the oxidative dechlorination
      of 2,4-dichlorophenol (I) to yield 1,2,4,5-tetrahydroxybenzene (VIII). The
      intermediate 1,2,4,5-tetrahydroxybenzene (VIII) is ring cleaved to produce, after
      subsequent oxidation, malonic acid. In the first step of the pathway, 2,4
      dichlorophenol (I) is oxidized to 2-chloro-1,4-benzoquinone (II) by either
      manganese peroxidase or lignin peroxidase. 2-Chloro-1,4-benzoquinone (II) is then
      reduced to 2-chloro-1,4-hydroquinone (III), and the latter is methylated to form
      the lignin peroxidase substrate 2-chloro-1,4-dimethoxybenzene (IV). 2-Chloro-1,4
      dimethoxybenzene (IV) is oxidized by lignin peroxidase to generate 2,5-dimethoxy
      1,4-benzoquinone (V), which is reduced to 2,5-dimethoxy-1,4-hydroquinone (VI).
      2,5-Dimethoxy-1,4-hydroquinone (VI) is oxidized by either peroxidase to generate
      2,5-dihydroxy-1,4-benzoquinone (VII) which is reduced to form the tetrahydroxy
      intermediate 1,2,4,5-tetrahydroxybenzene (VIII). In this pathway, the substrate
      is oxidatively dechlorinated by lignin peroxidase or manganese peroxidase in a
      reaction which produces a p-quinone. The p-quinone intermediate is then recycled
      by reduction and methylation reactions to regenerate an intermediate which is
      again a substrate for peroxidase-catalyzed oxidative dechlorination. This unique
      pathway apparently results in the removal of both chlorine atoms before ring
      cleavage occurs.

PMID- 1987126
TI  - Nucleotide sequence of the Escherichia coli recJ chromosomal region and
      construction of recJ-overexpression plasmids.
AB  - The nucleotide sequence of the recJ gene of Escherichia coli K-12 and two
      upstream coding regions was determined. Three regions were identified within
      these two upstream genes that exhibited weak to moderate promoter activity in
      fusions to the galK gene and are candidates for the recJ promoter. recJ appeared
      to be poorly translated: the recJ nucleotide sequence revealed a suboptimal
      initiation codon GUG, no discernible ribosome-binding consensus sequence, and
      relatively nonbiased synonymous codon usage. Comparison of the sequence of this
      region of the chromosome with DNA data bases identified the gene immediately
      downstream of recJ as prfB, which encodes translational release factor 2 and has
      been mapped near recJ at 62 min. No significant homology between recJ and other
      previously sequenced regions of DNA was detected. However, protein sequence
      comparisons with a gene upstream of recJ, denoted xprB, revealed significant
      homology with several site-specific recombination proteins. Its genetic function
      is presently unknown. Knowledge of the nucleotide sequence of recJ allowed the
      construction of a plasmid from which overexpression of RecJ protein could be
      induced. Supporting the notion that translation of recJ is limiting, a strong T7
      bacteriophage promoter upstream of recJ did not, by itself, allow high-level
      expression of RecJ protein. The addition of a ribosome-binding sequence fused to
      the initiator GTG of recJ in this construction was necessary to promote
      expression of high levels of RecJ protein.

PMID- 1987127
TI  - Detection of alternative nitrogenases in aerobic gram-negative nitrogen-fixing
      bacteria.
AB  - Strains of aerobic, microaerobic, nonsymbiotic, and symbiotic dinitrogen-fixing
      bacteria were screened for the presence of alternative nitrogenase (N2ase) genes
      by DNA hybridization between genomic DNA and DNA encoding structural genes for
      components 1 of three different enzymes. A nifDK gene probe was used as a control
      to test for the presence of the commonly occurring Mo-Fe N2ase, a vnfDGK gene
      probe was used to show the presence of V-Fe N2ase, and an anfDGK probe was used
      to detect Fe N2ase. Hitherto, all three enzymes have been identified in
      Azotobacter vinelandii OP, and all but the Fe N2ase are present in Azotobacter
      chroococcum ATCC 4412 (MCD1). Mo-Fe N2ase and V-Fe N2ase structural genes only
      were confirmed in this strain and in two other strains of A. chroococcum (ATCC
      480 and ATCC 9043). A similar pattern was observed with Azotobacter beijerinckii
      ATCC 19360 and Azotobacter nigricans ATCC 35009. Genes for all three systems are
      apparently present in two strains of Azotobacter paspali (ATCC 23367 and ATCC
      23833) and also in Azomonas agilis ATCC 7494. There was no good evidence for the
      existence of any genes other than Mo-Fe N2ase structural genes in several
      Rhizobium meliloti strains, cowpea Rhizobium strain 32H1, or Bradyrhizobium
      japonicum. Nitrogenase and nitrogenase genes in Azorhizobium caulinodans behaved
      in an intermediate fashion, showing (i) the formation of ethane from acetylene
      under Mo starvation, a characteristic of alternative nitrogenases, and (ii) a
      surprising degree of cross-hybridization to the vnfDGK, but not the anfDGK,
      probe. vnfDGK- and anfDGK-like sequences were not detected in two saccharolytic
      Pseudomonas species or Azospirillum brasilense Sp7. The occurrence of alternative
      N2ases seems restricted to members of the family Azotobacteraceae among the
      aerobic and microaerobic diazotrophs tested, suggesting that an ability to cope
      with O2 when fixing N2 may be an important factor influencing the distribution of
      alternative nitrogenases.

PMID- 1987130
TI  - Cloning and sequencing of the beta-lactam hydroxylase gene (cefF) from
      Streptomyces clavuligerus: gene duplication may have led to separate hydroxylase
      and expandase activities in the actinomycetes.
AB  - The deacetylcephalosporin C synthetase (hydroxylase) gene from Streptomyces
      clavuligerus has been cloned and sequenced. The open reading frame codes for a
      protein with an Mr of 34,584. The hydroxylase gene (cefF) is closely linked to
      the epimerase gene (cefD) and the expandase gene (cefE) and is transcribed in the
      opposite orientation. The hydroxylase and expandase genes are 59 and 71%
      identical at the amino acid and DNA levels, respectively. cefE and cefF may have
      arisen from a gene duplication in the actinomycetes.

PMID- 1987129
TI  - Genetic transformation in Streptococcus pneumoniae: nucleotide sequence analysis
      shows comA, a gene required for competence induction, to be a member of the
      bacterial ATP-dependent transport protein family.
AB  - The complete nucleotide sequence of comA, a gene required for induction of
      competence for genetic transformation in Streptococcus pneumoniae, was determined
      by using plasmid DNA templates and synthetic oligonucleotide primers. The
      sequence contained a single large open reading frame, ORF1, of 2,151 bp. ORF1 was
      included within the comAB locus previously mapped genetically and accounted for
      50% of its extent. The predicted molecular weight of the largest polypeptide
      encoded within ORF1, 80,290, coincided with that measured previously (77,000) for
      the product of in vitro transcription-translation of the cloned comA locus. A
      Shine-Dalgarno sequence (AAAGGAG, delta G = -14 kcal) lay immediately upstream of
      ORF1. A sequence (TTtAat-17 bp-TAaAAT) similar to the Escherichia coli sigma 70
      promoter consensus was located 410 bp upstream of ORF1. The deduced protein
      sequence of ComA showed a very strong similarity to the E. coli hemolysin
      secretion protein, HlyB, and strong similarities to other members of the family
      of ATP-dependent transport proteins, including the mammalian multidrug resistance
      P-glycoprotein. These similarities suggest that ComA functions in the transport
      of some molecule, possibly pneumococcal competence factor itself.

PMID- 1987128
TI  - Mutational analysis of a bacteriophage P4 late promoter.
AB  - Transcription from the late Psid promoter of satellite bacteriophage P4 is
      dependent on the bacterial RNA polymerase carrying the sigma 70 subunit and is
      positively regulated by the product of the P4 delta gene or the ogr gene of
      helper bacteriophage P2. Through deletion and mutational analyses of the Psid
      promoter, we identified mutations in the -10 region and in a region of hyphenated
      dyad symmetry centered around position -55 that inactivate Psid. Most of these
      mutations alter base pairs that are highly conserved in the five other delta
      activated P4 and P2 late promoters. We propose that the P4 delta and P2 ogr gene
      products bind the -55 region of the P4 and P2 late promoters.

PMID- 1987131
TI  - Chromogenic method for rapid isolation of recA-like mutants of gram-negative
      bacteria.
AB  - We have devised a rapid and widely applicable color test for detecting recA-like
      mutants of gram-negative bacteria. The technique depends on decreased expression
      of an Escherichia coli recA-lacZ fusion in recA mutants and uses a broad-host
      range plasmid to transfer the fusion gene into new species. We describe the
      isolation of a recA-like mutant of Pseudomonas syringae by this technique.

PMID- 1987132
TI  - Temperature sensitivity caused by missense suppressor supH and amber suppressor
      supP in Escherichia coli.
AB  - The temperature-sensitive missense suppressor supH and amber suppressor supP in
      Escherichia coli are mutations of the serU and leuX genes, respectively. The supH
      tRNA, tRNA(SerCAA), is expected to recognize UUG codons, which are normally read
      by tRNA(LeuCAA) and tRNA(LeuUAA), coded for by the leuX gene and the leuZ gene,
      respectively. We show that supP and supH are incompatible and that strains
      carrying both supP and a restrictive rpsL allele are temperature sensitive. It is
      suggested that the temperature sensitivity of both supH and supP strains is
      caused by deficient reading of UUG codons by tRNA(LeuUAA).

PMID- 1987133
TI  - Expression of the cloned Escherichia coli O9 rfb gene in various mutant strains
      of Salmonella typhimurium.
AB  - To investigate the effect of chromosomal mutation on the synthesis of rfe
      dependent Escherichia coli O9 lipopolysaccharide (LPS), the cloned E. coli O9 rfb
      gene was introduced into Salmonella typhimurium strains defective in various
      genes involved in the synthesis of LPS. When E. coli O9 rfb was introduced into
      S. typhimurium strains possessing defects in rfb or rfc, they synthesized E. coli
      O9 LPS on their cell surfaces. The rfe-defective mutant of S. typhimurium
      synthesized only very small amounts of E. coli O9 LPS after the introduction of
      E. coli O9 rfb. These results confirmed the widely accepted idea that the
      biosynthesis of E. coli O9-specific polysaccharide does not require rfc but
      requires rfe. By using an rfbT mutant of the E. coli O9 rfb gene, the mechanism
      of transfer of the synthesized E. coli O9-specific polysaccharide from antigen
      carrier lipid to the R-core of S. typhimurium was investigated. The rfbT mutant
      of the E. coli O9 rfb gene failed to direct the synthesis of E. coli O9 LPS in
      the rfc mutant strain of S. typhimurium, in which rfaL and rfbT functions are
      intact, but directed the synthesis of the precursor. Because the intact E. coli
      O9 rfb gene directed the synthesis of E. coli O9 LPS in the same strain, it was
      suggested that the rfaL product of S. typhimurium and rfbT product of E. coli O9
      cooperate to synthesize E. coli O9 LPS in S. typhimurium.

PMID- 1987134
TI  - The binding of cyclic AMP receptor protein to two lactose promoter sites is not
      cooperative in vitro.
AB  - The lactose promoter-operator region of Escherichia coli contains two binding
      sites for cyclic AMP receptor protein (CAP), two for the lactose repressor, and
      two for RNA polymerase. The high density of binding sites makes cooperative
      interactions between these proteins likely. In this study, we used the gel
      electrophoresis mobility shift assay and binding partition analysis techniques to
      determine whether the secondary CAP site influences the binding of CAP to the
      principal CAP site in the lactose promoter when both are present on a linear DNA
      molecule. Such an effect could occur through the formation of a bridged DNA-CAP
      DNA structure, through the interaction of CAP molecules bound to each of the
      sites, or through allosteric effects caused by CAP-mediated DNA bending. We
      found, however, that the interaction of CAP with these sites was not cooperative,
      indicating that CAP sites 1 and 2 bind CAP in an independent manner.

PMID- 1987135
TI  - Cloning and characterization of plasmid-encoded genes for the degradation of 1,2
      dichloro-, 1,4-dichloro-, and 1,2,4-trichlorobenzene of Pseudomonas sp. strain
      P51.
AB  - Pseudomonas sp. strain P51 is able to use 1,2-dichlorobenzene, 1,4
      dichlorobenzene, and 1,2,4-trichlorobenzene as sole carbon and energy sources.
      Two gene clusters involved in the degradation of these compounds were identified
      on a catabolic plasmid, pP51, with a size of 110 kb by using hybridization. They
      were further characterized by cloning in Escherichia coli, Pseudomonas putida
      KT2442, and Alcaligenes eutrophus JMP222. Expression studies in these organisms
      showed that the upper-pathway genes (tcbA and tcbB) code for the conversion of
      1,2-dichlorobenzene and 1,2,4-trichlorobenzene to 3,4-dichlorocatechol and 3,4,6
      trichlorocatechol, respectively, by means of a dioxygenase system and a
      dehydrogenase. The lower-pathway genes have the order tcbC-tcbD-tcbE and encode a
      catechol 1,2-dioxygenase II, a cycloisomerase II, and a hydrolase II,
      respectively. The combined action of these enzymes degrades 3,4-dichlorocatechol
      and 3,4,6-trichlorocatechol to a chloromaleylacetic acid. The release of one
      chlorine atom from 3,4-dichlorocatechol takes place during lactonization of 2,3
      dichloromuconic acid.

PMID- 1987136
TI  - Characterization of a phage-plasmid hybrid (phasyl) with two independent origins
      of replication isolated from Escherichia coli.
AB  - The phage-plasmid hybrid phasyl can replicate as a phage in the presence of a
      filamentous phage of Escherichia coli (M13, fl, fd). The extragenic region of
      phasyl shows homology with the plus and the minus origins of filamentous phages.
      Insertion of a Cmr fragment into the plus origin or of a Kmr fragment into the
      minus origin resulted in a reduced transduction frequency, while insertion into
      other parts of the extragenic region did not. This suggests that phagelike
      replication of phasyl is mediated by an origin that coincides with the two
      homologous elements in the extragenic region. Autonomous replication of phasyl
      occurs from a second origin (oriA) that is located between positions 297 and 636.
      This fragment mediates replication if the Arp protein is supplied in trans. Arp
      is the only phage-encoded protein and is essential for plasmidlike replication.
      No sequence homology to other known origins was found. Phasyl derivatives with
      either one of the two origins inactivated can be rescued via the alternative
      replication mode, suggesting that the two replication pathways are independent.

PMID- 1987137
TI  - Transcription of Clostridium thermocellum endoglucanase genes celF and celD.
AB  - Transcripts of the Clostridium thermocellum endoglucanase genes celF and celD,
      encoding endoglucanases F and D, respectively, were characterized. The size of
      the mRNAs was about 2.35 kb for celF and 2.1 kb for celD, indicating
      monocistronic transcription of both genes. A unique 5' end, located 218 bp
      upstream from the initiation codon, was found for celF mRNA. No convincing
      homology could be identified between the sequence upstream from the celF 5' end
      and other procaryotic promoters. Two 5' ends, located 124 and 294 bp upstream
      from the initiation codon, were mapped for celD mRNA. The -10 and the -35
      sequences preceding the ATG-distal 5' end of celD mRNA were homologous to the
      consensus sequence of Bacillus subtilis sigma 43 promoters. The sequence upstream
      from the ATG-proximal 5' end had some similarity with the -10 sequence of B.
      subtilis sigma 28 promoters. During growth on cellobiose, the 5' end of celD
      transcripts was found predominantly at the -124 site during the late exponential
      phase but almost exclusively at the -294 site during the early stationary phase.
      The kinetics of appearance of celA, celC, celD, and celF mRNA was followed by dot
      blot analysis. Transcripts of celA, celD, and celF were detected during late
      exponential and early stationary phase. In contrast, the celC transcript was
      detected almost exclusively during early stationary phase. Since growth was
      limited by the availability of cellobiose, the results suggest that the genes are
      regulated by a mechanism analogous to catabolite repression.

PMID- 1987138
TI  - delta-Aminolevulinic acid dehydratase deficiency can cause delta-aminolevulinate
      auxotrophy in Escherichia coli.
AB  - Ethylmethane sulfonate-induced mutants of several Escherichia coli strains that
      required delta-aminolevulinic acid (ALA) for growth were isolated by penicillin
      enrichment or by selection for respiratory-defective strains resistant to the
      aminoglycoside antibiotic kanamycin. Three classes of mutants were obtained. Two
      thirds of the strains were mutants in hemA. Representative of a third of the
      mutations was the hem-201 mutation. This mutation was mapped to min 8.6 to 8.7.
      Complementation of the auxotrophic phenotype by wild-type DNA from the
      corresponding phage 8F10 allowed the isolation of the gene. DNA sequence analysis
      revealed that the hem-201 gene encoded ALA dehydratase and was similar to a known
      hemB gene of E. coli. Complementation studies of hem-201 and hemB1 mutant strains
      with various hem-201 gene subfragments showed that hem-201 and the previously
      reported hemB1 mutation are in the same gene and that no other gene is required
      to complement the hem-201 mutant. ALA-forming activity from glutamate could not
      be detected by in vitro or in vivo assays. Extracts of hem-201 cells had
      drastically reduced ALA dehydratase levels, while cells transformed with the
      plasmid-encoded wild-type gene possessed highly elevated enzyme levels. The ALA
      requirement for growth, the lack of any ALA-forming enzymatic activity, and
      greatly reduced ALA dehydratase activity of the hem-201 strain suggest that a
      diffusible product of an enzyme in the heme biosynthetic pathway after ALA
      formation is involved in positive regulation of ALA biosynthesis. In contrast to
      the hem-201 mutant, previously isolated hemB mutants were not ALA auxotrophs and
      had no detectable ALA dehydratase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1987139
TI  - Primary sequence of the Escherichia coli fadL gene encoding an outer membrane
      protein required for long-chain fatty acid transport.
AB  - The fadL gene of Escherichia coli encodes an outer membrane protein (FadL) that
      plays a central role in the uptake of exogenous long-chain fatty acids. The
      nucleotide sequence of the fadL gene revealed a single open reading frame of
      1,344 bp encoding a protein with 448 amino acid residues and a molecular weight
      of 48,831. The transcriptional start, analyzed by primer extension, was shown to
      be 95 bp upstream from the translational start. Apparent -10 and -35 regions were
      found at -12 and -37 bp upstream from the transcriptional start. Three regions
      with hyphenated dyad symmetry (two between the transcriptional start and the
      translational start and one upstream from the -10 and -35 regions) were
      identified that may play a role in the expression of fadL. The protein product of
      the fadL gene contained a signal sequence and signal peptidase I cleavage site
      similar to that defined for other E. coli outer membrane proteins. The N-terminal
      sequence of mature FadL protein was determined by automated amino acid sequencing
      of protein purified from the outer membrane of a strain harboring fadL under the
      control of a T7 RNA polymerase-responsive promoter. This amino acid sequence, Ala
      Gly-Phe-Gln-Leu-Asn-Glu-Phe-Ser-Ser, verified the signal peptidase I cleavage
      site on pre-FadL and confirmed the N-terminal amino acid sequence of FadL
      predicted from the DNA sequence. Mature FadL contained 421 amino acid residues,
      giving a molecular weight of 45,969. The amino acid composition of FadL deduced
      from the DNA sequence suggested that this protein contained an abundance of
      hydrophobic amino acid residues and lacked cysteinyl residues. The hydrophobic
      amino acids within FadL were predicted to contribute to at least five regions of
      the protein with an overall hydrophobic character. The amino acid sequence of
      FadL was used to search GenBank for other proteins with amino acid sequence
      homology. These data demonstrated that FadL and the heat-modifiable outer
      membrane protein P1 of Haemophilus influenzae type b were 60.5% conserved and
      42.0% identical over 438 amino acid residues.

PMID- 1987140
TI  - Phosphatidylglyceroylalkylamine, a novel phosphoglycolipid precursor in
      Deinococcus radiodurans.
AB  - We report here the structure of a previously uncharacterized phospholipid in the
      radiation-resistant bacterium Deinococcus radiodurans. This phospholipid,
      designated lipid 4, was shown by chemical analysis, HF hydrolysis, and nuclear
      magnetic resonance spectroscopy to be phosphatidylglyceroylalkylamine. Lipid 4
      thus contains the unusual lipid constituents glyceric acid and alkylamines, which
      have previously been identified in two complex phosphoglycolipids from this
      organism. By [32P]phosphate pulse-chase labeling techniques, lipid 4 was shown to
      be the precursor of the complex phosphoglycolipids alpha-galactosyl- and alpha-N
      acetylglucosaminylphosphatidylglyceroylalkylamine. While
      phosphatidylglyceroylalkylamine is rapidly biosynthesized from Pi, its subsequent
      glycosylation occurs much more slowly. Therefore, we conclude that the final
      glycosylation step is the rate-limiting event in the biosynthesis of the complex
      phosphoglycolipids alpha-galactosyl- and alpha-N-acetylglucosaminyl
      phosphatidylglyceroylalkylamine.

PMID- 1987142
TI  - Choline oxidase, a catabolic enzyme in Arthrobacter pascens, facilitates
      adaptation to osmotic stress in Escherichia coli.
AB  - Choline oxidase (EC 1.1.3.17) is a bifunctional enzyme that is capable of
      catalyzing glycine betaine biosynthesis from choline via betaine aldehyde. A gene
      (cox) encoding this enzyme in the gram-positive soil bacterium Arthrobacter
      pascens was isolated and characterized. This gene is contained within a 1.9-kb
      fragment that encodes a polypeptide of approximately 66 kDa. Transfer of this
      gene to an Escherichia coli mutant that is defective in betaine biosynthesis
      resulted in an osmotolerant phenotype. This phenotype was associated with the
      ability of the host to synthesize and assemble an enzymatically active choline
      oxidase that could catalyze biosynthesis of glycine betaine from an exogenous
      supply of choline. Although glycine betaine functions as an osmolyte in several
      different organisms, it was not found to have this role in A. pascens. Instead,
      both choline and glycine betaine were utilized as carbon sources. In A. pascens
      synthesis and activity of choline oxidase were modulated by carbon sources and
      were susceptible to catabolite repression. Thus, cox, a gene concerned with
      carbon utilization in A. pascens, was found to play a role in adaptation to an
      environmental stress in a heterologous organism. In addition to providing a
      possible means of manipulating osmotolerance in other organisms, the cox gene
      offers a model system for the study of choline oxidation, an important metabolic
      process in both procaryotes and eucaryotes.

PMID- 1987141
TI  - Molecular characterization and expression analysis of the anthranilate synthase
      gene of Pseudomonas syringae subsp. savastanoi.
AB  - The trpE gene, which encodes the large component of the enzyme anthranilate
      synthase, was isolated from a Pseudomonas syringae subsp. savastanoi (P.
      savastanoi) cosmid library. Cosmids that complemented an Escherichia coli trpE
      mutation contained a gene whose product is 86% homologous at the deduced amino
      acid level to TrpE of Pseudomonas aeruginosa and Pseudomonas putida. Amino acid
      sequence comparison with other TrpE sequences revealed the existence of conserved
      regions between the procaryotic and eucaryotic polypeptide sequences analyzed,
      regions that might be of functional importance. We also report on studies on the
      expression pattern of this gene. We analyzed the promoter activity of a
      trpE::lacZ transcriptional fusion, the relative amount of trpE steady-state mRNA,
      and the activity of anthranilate synthase from cells grown in minimal medium with
      or without exogenously added tryptophan and in complete medium. We concluded that
      under the conditions tested, expression of the trpE gene of P. savastanoi is
      independent of the concentration of tryptophan in the culture medium.
      Implications of such an expression pattern on the virulence of this bacterium are
      discussed.

PMID- 1987143
TI  - Molecular analysis of lipoteichoic acid from Streptococcus agalactiae.
AB  - A method for the analysis of lipoteichoic acid (LTA) by polyacrylamide gel
      electrophoresis (PAGE) is described. Purified LTA from Streptococcus agalactiae
      tended to smear in the upper two-thirds of a 30 to 40% linear polyacrylamide gel,
      while the chemically deacylated form (cdLTA) migrated as a ladder of discrete
      bands, reminiscent of lipopolysaccharides. The deacylated polymer appeared to
      separate in this system on the basis of size, as evident from results obtained
      from PAGE analysis of cdLTA subjected to limited acid hydrolysis and LTA that had
      been fractionated by gel filtration. A survey of cdLTA from other streptococci
      revealed similarities in molecular weight ranges. The polymer from Enterococcus
      hirae was of a higher molecular weight. This procedure was used to examine the
      effect of penicillin and chloramphenicol on the synthesis, turnover, and
      heterogeneity of LTA in S. agalactiae. Penicillin appeared to enhance LTA
      synthesis while causing the release of this polymer into the supernatant fluid.
      In contrast, chloramphenicol inhibited the synthesis of this molecule and
      resulted in its depletion from the cell surface. Penicillin did not alter the
      heterogeneity of this polymer, but chloramphenicol caused an apparent shift to a
      lower-molecular-weight from of the LTA, as determined by PAGE. This shift in the
      heterogeneity of LTA did not appear to be due to increased carbohydrate
      substitution, since chloramphenicol did not alter the electrophoretic migration
      profile of LTA from E. hirae. From a pulse-chase study, it was determined that
      LTA was released as a consequence of deacylation.

PMID- 1987144
TI  - Specific cell components of Bacteroides gingivalis mediate binding and
      degradation of human fibrinogen.
AB  - Bacteroides (Porphyromonas) gingivalis, which has been implicated as an etiologic
      agent in human periodontal diseases, has been shown to bind and degrade human
      fibrinogen. B. gingivalis strains bind fibrinogen reversibly and with high
      affinity and bind to a specific region of the fibrinogen molecule that appears to
      be located between the D and E domains (M. S. Lantz, R. D. Allen, P. Bounelis, L.
      M. Switalski, and M. Hook, J. Bacteriol. 172:716-726, 1990). We now report that
      human fibrinogen is bound and then degraded by specific B. gingivalis components
      that appear to be localized at the cell surface. Fibrinogen binding to bacterial
      cells occurred at 4, 22, and 37 degrees C. A functional fibrinogen-binding
      component (Mr, 150,000) was identified when sodium dodecyl sulfate-solubilized
      bacteria were fractionated by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis, transferred to nitrocellulose membranes, and probed with 125I
      fibrinogen. Fibrinogen degradation did not occur at 4 degrees C but did occur at
      22 and 37 degrees C. When bacteria and iodinated fibrinogen were incubated at 37
      degrees C, two major fibrinogen fragments (Mr, 97,000 and 50,000) accumulated in
      incubation mixture supernatant fractions. Two major fibrinogen-degrading
      components (Mr, 120,000 and 150,000) have been identified by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis in substrate-containing gels.
      Fibrinogen degradation by the Mr-120,000 and -150,000 proteases was enhanced by
      reducing agents, completely inhibited by N-alpha-p-tosyl-L-lysyl chloromethyl
      ketone, and partially inhibited by n-ethyl maleimide, suggesting that these
      enzymes are thiol-dependent proteases with trypsinlike substrate specificity. The
      fibrinogen-binding component could be separated from the fibrinogen-degrading
      components by selective solubilization of bacteria in sodium deoxycholate.

PMID- 1987146
TI  - Nucleotide sequence of Escherichia coli katE, which encodes catalase HPII.
AB  - A 3,466-bp nucleotide sequence containing the katE gene of Escherichia coli has
      been determined. An open reading frame of 2,259 bp was found and was preceded by
      a potential ribosome-binding site. The predicted N-terminal sequence agreed with
      the sequence determined by direct amino acid sequencing, and the predicted
      direction of transcription was confirmed by expression of the gene cloned in both
      directions behind a T7 promoter. The start site of transcription was determined
      to be 127 bp upstream from the start of the open reading frame, and a potential
      RNA polymerase-binding site similar to a sequence preceding the xthA gene, which
      is also controlled by the KatF protein, was identified. The predicted sequence of
      the 753-amino-acid protein was compared with known sequences of other catalases,
      revealing significant similarity to the shorter catalases, including the residues
      in the putative active site and residues involved in heme binding.

PMID- 1987145
TI  - Isolation and biochemical and molecular analyses of a species-specific protein
      antigen from the gastric pathogen Helicobacter pylori.
AB  - A protein of Mr 26,000 which was present in large quantities in extracts of cells
      of Helicobacter pylori was purified to homogeneity by ammonium sulfate
      precipitation followed by gel filtration and reversed-phase chromatography or
      anion-exchange chromatography. The protein appeared to be associated with the
      soluble fraction of the cell, and antibodies raised against the protein were
      reactive with whole-cell lysates of a variety of H. pylori strains in a simple
      immunodot blot assay. This reaction was species specific. Protein sequence
      determination of the amino terminus and internal cyanogen bromide fragments and
      amino acid composition analysis were performed. An oligonucleotide derived from
      these data was used to clone a fragment encoding most of the coding sequence.
      Expression in Escherichia coli was dependent on vector promoters. The DNA
      sequence of the fragment was determined. DNA probes derived from the cloned
      fragment hybridized to genomic DNA of all H. pylori strains tested, but not to
      DNAs of Helicobacter mustelae, Wolinella succinogenes, various Campylobacter
      species, and a panel of gram-negative enteric bacteria. The apparent uniqueness
      of this protein may be exploited for the development of species-specific
      diagnostics for this gastric pathogen.

PMID- 1987147
TI  - Isolation and characterization of a filamentous viruslike particle from
      Clostridium acetobutylicum NCIB 6444.
AB  - A single-stranded 6.6-kb DNA molecule complexed with protein was recovered from
      the supernatant of Clostridium acetobutylicum NCIB 6444. Electron microscopic
      examination of the DNA-protein complex revealed the presence of a filamentous
      viruslike particle, which was designated CAK1. The possible double-stranded
      plasmidlike replicative form and the single-stranded prophage were also recovered
      from the cell culture following alkaline lysis. CAK1 was released from the C.
      acetobutylicum cell culture in the absence of cell lysis. Polyethylene glycol
      NaCl coprecipitation of the DNA-protein complex revealed the presence of single
      stranded DNA complexed with protein in a manner rendering the DNA resistant to
      Bal 31 exonuclease. Proteinase treatment of CsCl density gradient-purified CAK1
      resulted in recovery of DNase-sensitive single-stranded DNA. Tricine-sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis of CAK1 demonstrated the
      presence of a 5-kDa major coat protein. Hybridization data indicated that the
      single-stranded DNA from CAK1 has homology with the M13 phage of Escherichia
      coli. An examination of various physical properties of CAK1 suggests that it is
      similar to the filamentous phage recovered from gram-negative microorganisms.
      Although infectivity or inducibility of CAK1 could not be demonstrated, to our
      knowledge this represents the first report of a nonlytic filamentous viruslike
      particle containing single-stranded DNA being recovered from a gram-positive
      bacterium.

PMID- 1987148
TI  - Cloning and nucleic acid sequence of the Salmonella typhimurium pncB gene and
      structure of nicotinate phosphoribosyltransferase.
AB  - The pncB gene of Salmonella typhimurium, encoding nicotinate
      phosphoribosyltransferase (NAPRTase), was cloned on a 4.7-kb Sau3A fragment. The
      gene contains a 1,200-bp open reading frame coding for a 400-residue protein.
      Amino acid sequencing of the amino-terminal and two interior peptides of the
      purified protein confirmed the deduced sequence and revealed that the amino
      terminal methionine residue was removed, giving a 399-residue mature protein of
      Mr 45,512. No signal sequence was observed in the predicted NAPRTase primary
      structure, suggesting that the enzyme is not periplasmic. The protein does not
      demonstrate clear sequence similarity to the other seven
      phosphoribosyltransferases of known primary structure and frustrates attempts to
      define a consensus 5-phosphoribosyl-1-pyrophosphate-binding region. The NAPRTase
      reaction is ATP stimulated, and the protein contains a carboxy-terminal sequence
      diagnostic of an ATP-binding site. An inverted repeat of the sequence TAAACAA
      observed in the proposed promoter region of pncB is also present in the promoter
      of nadA, which, like pncB, is also regulated by the NadR (NadI) repressor. The
      sequence may thus define an NadR repressor-binding site.

PMID- 1987149
TI  - Nucleotide sequence and analysis of a gene encoding anthranilate synthase
      component I in Spirochaeta aurantia.
AB  - A Spirochaeta aurantia DNA fragment containing the trpE gene and flanking
      chromosomal DNA was cloned, and the sequence of the trpE structural gene plus 870
      bp upstream and 1,257 bp downstream of trpE was determined. The S. aurantia trpE
      gene codes for a polypeptide of 482 amino acid residues with a predicted
      molecular weight of 53,629 that showed sequence similarity to TrpE proteins from
      other organisms. The S. aurantia TrpE polypeptide is not more closely related to
      the other published spirochete TrpE sequence (that of Leptospira biflexa) than to
      TrpE polypeptides of other bacteria. Two additional complete open reading frames
      and one partial open reading frame were identified in the sequenced DNA. One of
      the complete open reading frames and the partial open reading frame are upstream
      of trpE and are encoded on the DNA strand opposite that containing trpE. The
      other open reading frame is downstream of trpE and on the same DNA strand as
      trpE. On the basis of the results of a protein sequence data base search, it
      appears that trpE is the only tryptophan biosynthesis gene in the sequenced DNA.
      This is in contrast to L. biflexa, in which trpE is separated from trpG by only
      64 bp.

PMID- 1987150
TI  - Dual regulation of the ugp operon by phosphate and carbon starvation at two
      interspaced promoters.
AB  - The ugp operon of Escherichia coli includes genes involved in the uptake of sn
      glycerol-3-phosphate and glycerophosphoryl diesters and belongs to the pho
      regulon which is induced by phosphate limitation. This operon has two
      transcriptional initiation sites, as determined by S1 nuclease mapping of the in
      vivo transcripts. The downstream promoter has multiple copies of the pho box, the
      consensus sequence shared by the pho promoters; the upstream promoter has a
      consensus sequence for the promoters regulated by cyclic AMP and its receptor
      protein, CRP. PhoB protein, which is the transcriptional activator for the pho
      regulon, protected the regulatory region with the pho boxes in DNase I
      footprinting experiments and activated transcription from the downstream promoter
      in vitro. Studies with transcriptional fusions between ugp and a promoterless
      gene for chloramphenicol acetyltransferase show that the upstream promoter is
      induced by carbon starvation in a manner that required the cya and crp genes.
      PhoB protein may act as a repressor for this upstream promoter, which also
      overlaps the upstream third pho box. The downstream promoter was induced by
      phosphate starvation and requires the PhoB protein for its activation as do the
      other pho regulon promoters. These results suggest that the two promoters
      function alternately in responding to phosphate or carbon starvation, thus
      providing the cell with a means to adapt to these physiological stresses.

PMID- 1987151
TI  - Cloning, sequence, and expression of a lipase gene from Pseudomonas cepacia:
      lipase production in heterologous hosts requires two Pseudomonas genes.
AB  - The lipA gene encoding an extracellular lipase from Pseudomonas cepacia was
      cloned and sequenced. Downstream from the lipase gene an open reading frame was
      identified, and the corresponding gene was named limA. lipA was well expressed
      only in the presence of limA. limA exerts its effect both in cis and in trans and
      therefore produces a diffusible gene product, presumably a protein of 344 amino
      acids. Replacement of the lipA expression signals (promoter, ribosome-binding
      site, and signal peptide-coding sequences) by heterologous signals from gram
      positive bacteria still resulted in limA-dependent lipA expression in Escherichia
      coli, Bacillus subtilis, and Streptomyces lividans.

PMID- 1987152
TI  - The Vibrio fischeri LuxR protein is capable of bidirectional stimulation of
      transcription and both positive and negative regulation of the luxR gene.
AB  - Regulation of the genes required for bioluminescence in the marine bacterium
      Vibrio fischeri (the lux regulon) is a complex process requiring coordination of
      several systems. The primary level of regulation is mediated by a positive
      regulatory protein, LuxR, and a small diffusible molecule, N-(3-oxo-hexanoyl)
      homoserine lactone, termed autoinducer. Transcription of the luxR gene, which
      encodes the regulatory protein, is positively regulated by the cyclic AMP-CAP
      system. The lux regulon of V. fischeri consists of two divergently transcribed
      operons designated operonL and operonR. Transcription of the rightward operon
      (operonR; luxICDABE), consisting of the genes required for autoinducer synthesis
      (luxI) and light production (luxCDABE), is activated by LuxR in an autoinducer
      dependent fashion. The leftward operon (operonL) consists of a single known gene,
      luxR. The LuxR protein has also been shown to decrease transcription of operonL
      through an autoinducer-dependent mechanism, thereby negatively regulating its own
      synthesis. In this paper we demonstrate that the autoinducer-dependent repression
      of operonL transcription requires not only LuxR but also DNA sequences within
      operonR which occur upstream of the promoter for operonL. In the absence of these
      DNA sequences, the LuxR protein causes an autoinducer-dependent activation of
      transcription of operonL. The lux operator, located in the control region between
      the two operons, was required for both the positive and negative autoinducer
      dependent responses. By titration of high levels of LuxR supplied in trans with
      synthetic autoinducer, we found that low levels of autoinducer could elicit a
      positive response even in the presence of the negative-acting DNA sequences,
      while higher levels of autoinducer resulted in a negative response. Without these
      DNA sequences in operonR, LuxR and autoinducer stimulated transcription
      regardless of the level of autoinducer. These results suggest that a switch
      between stimulation and repression of operonL transcription is mediated by the
      levels of the LuxR-autoinducer complex, which in these experiments reflects the
      level of autoinducer in the growth medium.

PMID- 1987153
TI  - Suppression of a mutation in OmpR at the putative phosphorylation center by a
      mutant EnvZ protein in Escherichia coli.
AB  - Phosphorylation of OmpR, a transcription activator for ompF and ompC expression,
      is essential for its function and has been shown to be mediated in vitro by EnvZ,
      a transmembrane sensory receptor protein. On the basis of the three-dimensional
      structure of CheY which has an extensive sequence similarity with OmpR, three
      aspartic residues, D11, D12, and D55, of OmpR are considered to form a triacidic
      pocket serving as the phosphorylation center. When these aspartic acid residues
      were replaced with asparagine (D11N) or glutamine (D12Q and D55Q), ompF and ompC
      expression was almost completely blocked. Two pseudorevertants of the D11N
      mutation were isolated: one of them is a mutation in EnvZ (G240E), and the other
      is a mutation in OmpR (S48F). The envZ mutation (G240E) by itself was found to
      confer a phenotype very similar to that of the well known envZ11 mutation
      (T247R), suggesting that EnvZ (G240E) is an elevated kinase for OmpR. Consistent
      with this notion, EnvZ (T247R) was also able to suppress the D11N mutation in
      OmpR. An in vitro phosphorylation study showed that while the wild-type OmpR was
      phosphorylated by EnvZ, the D11N OmpR was not. These results suggest that the
      D11N mutation alters OmpR conformation in such a way that OmpR is very poorly
      phosphorylated by EnvZ. On the basis of the in vivo and in vitro analysis, the
      mechanisms by which the G240E mutation in EnvZ and the S48F mutation in OmpR
      suppress the D11N mutation in OmpR are discussed.

PMID- 1987154
TI  - Chemical characterization of Campylobacter jejuni lipopolysaccharides containing
      N-acetylneuraminic acid and 2,3-diamino-2,3-dideoxy-D-glucose.
AB  - Lipopolysaccharides (LPS) of four nonencapsulated strains of the human enteric
      pathogen Campylobacter jejuni were chemically characterized. When applied to two
      of the strains, extraction by a modified phenol-chloroform-petroleum ether method
      (H. Brade and C. Galanos, Eur. J. Biochem. 122:233-237, 1982) gave better yields
      of LPS than did extraction by the conventional hot phenol-water technique.
      Constituents common to all LPS were D-glucose, D-galactose, L-glycero-D-manno
      heptose, 3-deoxy-D-manno-2-octulosonic acid, D-glucuronic acid, D-galactosamine,
      and phosphorylethanolamine. Phosphate was present in a relatively high amount. In
      addition, the LPS of three strains contained N-acetylneuraminic acid, whereas the
      LPS of the strain lacking this component contained 3-amino-3,6-dideoxy-D-glucose.
      The lipid A component contained phosphate with D-glucosamine and 2,3-diamino-2,3
      dideoxy-D-glucose as the major amino sugars. Ethanolamine-phosphate was present
      also. The major fatty acids were ester- and amide-bound 3-hydroxytetradecanoic
      and ester-bound hexadecanoic acids, with a minor amount of ester-bound
      tetradecanoic acid. This is the first report of N-acetylneuraminic acid in the
      oligosaccharide moiety and diaminoglucose in the lipid A of C. jejuni LPS.

PMID- 1987155
TI  - Glycosylation and structure of the yeast MF alpha 1 alpha-factor precursor is
      important for efficient transport through the secretory pathway.
AB  - The MF alpha 1 gene encodes a precursor, prepro-alpha-factor, that undergoes
      several proteolytic processing steps within the classical secretory pathway to
      produce the mature peptide pheromone, alpha-factor. To investigate the role of
      structural features of the MF alpha 1 precursor in alpha-factor production, we
      analyzed the effect of mf alpha 1 mutations that alter precursor structure in a
      number of ways. These mutations resulted in decreased alpha-factor secretion and
      intracellular accumulation of pro-alpha-factor. With the exception of the mutant
      lacking all three N glycosylation sites, the pro-alpha-factor forms that
      accumulated were core glycosylated but had not yet undergone the addition of
      outer chain carbohydrate. The delay, therefore, occurred at a step prior to the
      first proteolytic processing step involved in maturation of the precursor and was
      probably due to inefficient endoplasmic reticulum-to-Golgi transport. Elimination
      of all three N-glycosylation sites caused a delay in disappearance of
      intracellular precursor, and alpha-factor secretion was also slowed. These data
      indicate that N glycosylation is important but not essential for transport of the
      precursor through the secretory pathway. The decreased alpha-factor secretion and
      increased precursor accumulation seen with many different structural changes of
      pro-alpha-factor indicate that the secretory pathway is extremely sensitive to
      changes in precursor structure. This sensitivity could cause inefficient
      secretion of heterologous proteins and hybrids between MF alpha 1 and
      heterologous proteins in yeast cells.

PMID- 1987156
TI  - Modification of the properties of a Ruminococcus albus endo-1,4-beta-glucanase by
      gene truncation.
AB  - An endo-1,4-beta-glucanase (EgI) gene isolated from Ruminococcus albus was
      deleted at the 5'-flanking region by gene truncation or at the 3'-flanking region
      by insertion of an omega (omega) fragment with a universal stop codon at the
      EcoRI or BamHI site. These modified genes were integrated into pUC vectors to
      construct chimera plasmids for Escherichia coli. The truncated EgIs were produced
      from transformants (E. coli) harboring the chimera plasmids. An EgI with a 15
      amino-acid N-terminal deletion exibited higher activity at lower pH and
      temperature compared with the activity of the original EgI. The EgIs with 59- and
      75-amino-acid deletions from the N and C terminals, respectively, had no
      activity, indicating that both terminal moieties are essential for enzyme
      activity.

PMID- 1987157
TI  - Localization of the terminal steps of O-antigen synthesis in Salmonella
      typhimurium.
AB  - Previous immunoelectron microscopic studies have shown that both the final
      intermediate in O-antigen synthesis, undecaprenol-linked O polymer, and newly
      synthesized O-antigenic lipopolysaccharide are localized to the periplasmic face
      of the inner membrane (C. A. Mulford and M. J. Osborn, Proc. Natl. Acad. Sci. USA
      80:1159-1163, 1983). In vivo pulse-chase experiments now provide further evidence
      that attachment of O antigen to core lipopolysaccharide, as well as
      polymerization of O-specific polysaccharide chains, takes place at the
      periplasmic face of the membrane. Mutants doubly conditional in
      lipopolysaccharide synthesis [kdsA(Ts) pmi] were constructed in which synthesis
      of core lipopolysaccharide and O antigen are temperature sensitive and mannose
      dependent, respectively. Periplasmic orientation of O antigen:core
      lipopolysaccharide ligase was established by experiments showing rapid chase of
      undecaprenol-linked O polymer, previously accumulated at 42 degrees C in the
      absence of core synthesis, into lipopolysaccharide following resumption of core
      formation at 30 degrees C. In addition, chase of the monomeric O-specific
      tetrasaccharide unit into lipopolysaccharide was found in similar experiments in
      an O-polymerase-negative [rfc kdsA(Ts) pmi] mutant, suggesting that
      polymerization of O chains also occurs at the external face of the inner
      membrane.

PMID- 1987158
TI  - The exoD gene of Rhizobium meliloti encodes a novel function needed for alfalfa
      nodule invasion.
AB  - During the symbiotic interaction between alfalfa and the nitrogen-fixing
      bacterium Rhizobium meliloti, the bacterium induces the formation of nodules on
      the plant roots and then invades these nodules. Among the bacterial genes
      required for nodule invasion are the exo genes, involved in production of an
      extracellular polysaccharide, and the ndv genes, needed for production of a
      periplasmic cyclic glucan. Mutations in the exoD gene result in altered
      exopolysaccharide production and in a nodule invasion defect. In this work we
      show that the stage of symbiotic arrest of exoD mutants is similar to that of
      other exo and ndv mutants. However, the effects of exoD mutations on
      exopolysaccharide production and growth on various media are different from the
      effects of other exo and ndv mutations. Finally, exoD mutations behave
      differently from other exo mutations in their ability to be suppressed or
      complemented extracellularly. The results suggest that exoD represents a new
      class of Rhizobium genes required for nodule invasion, distinct from the other
      exo genes and the ndv genes. We discuss models for the function of exoD.

PMID- 1987159
TI  - Genetic analysis of potassium transport loci in Escherichia coli: evidence for
      three constitutive systems mediating uptake potassium.
AB  - The analysis of mutants of Escherichia coli that require elevated concentrations
      of K+ for growth has revealed two new genes, trkG, near minute 30 within the
      cryptic rac prophage, and trkH, near minute 87, the products of which affect
      constitutive K+ transport. The analysis of these and other trk mutations suggests
      that high rates of transport, previously considered to represent the activity of
      a single system, named TrkA, appear to be the sum of two systems, here named TrkG
      and TrkH. Each of these two is absolutely dependent on the product of the trkA
      gene, a cytoplasmic protein associated with the inner membrane (D. Bossemeyer, A.
      Borchard, D. C. Dosch, G. C. Helmer, W. Epstein, I. R. Booth, and E. P. Bakker,
      J. Biol. Chem. 264:16403-16410, 1989). The TrkH system is also dependent on the
      products of the trkH and trkE genes, while the TrkG system is also dependent on
      the product of the trkG gene and partially dependent on the product of the trkE
      gene. It is suggested that the trkH and trkG products are membrane proteins that
      form the transmembrane path for the K+ movement of the respective systems. Two
      mutations altering the trkA product reduce the affinity for K+ of both TrkG and
      TrkH, indicating that changes in peripheral protein can alter the conformation of
      the sites at which K+ is bound prior to transport. The TrkD system has a
      relatively modest rate of transport, is dependent solely on the product of the
      trkD gene, and is the sole saturable system for Cs+ uptake in this species (D.
      Bossemeyer, A. Schlosser, and E. P. Bakker, J. Bacteriol. 171:2219-2221, 1989).

PMID- 1987160
TI  - 16S ribosomal DNA amplification for phylogenetic study.
AB  - A set of oligonucleotide primers capable of initiating enzymatic amplification
      (polymerase chain reaction) on a phylogenetically and taxonomically wide range of
      bacteria is described along with methods for their use and examples. One pair of
      primers is capable of amplifying nearly full-length 16S ribosomal DNA (rDNA) from
      many bacterial genera; the additional primers are useful for various exceptional
      sequences. Methods for purification of amplified material, direct sequencing,
      cloning, sequencing, and transcription are outlined. An obligate intracellular
      parasite of bovine erythrocytes, Anaplasma marginale, is used as an example; its
      16S rDNA was amplified, cloned, sequenced, and phylogenetically placed.
      Anaplasmas are related to the genera Rickettsia and Ehrlichia. In addition, 16S
      rDNAs from several species were readily amplified from material found in
      lyophilized ampoules from the American Type Culture Collection. By use of this
      method, the phylogenetic study of extremely fastidious or highly pathogenic
      bacterial species can be carried out without the need to culture them. In theory,
      any gene segment for which polymerase chain reaction primer design is possible
      can be derived from a readily obtainable lyophilized bacterial culture.

PMID- 1987162
TI  - Direct proof of a "more-than-single-layered" peptidoglycan architecture of
      Escherichia coli W7: a neutron small-angle scattering study.
AB  - A neutron small-angle scattering study was performed to determine the thickness
      and the scattering density profile of isolated peptidoglycan sacculi of
      Escherichia coli W7 in aqueous suspension (D2O). The maximum thickness (7 +/- 0.5
      nm) of the sacculus from the exponential-phase cells was large enough to suggest
      the existence of a more-than-single-layered architecture. The experimental
      density profile across the thickness of the sacculus did not allow an unambiguous
      differentiation between a single-layered architecture characterized by completely
      extended peptide side chains projecting from the sugar strands or, alternatively,
      a partially triple layered structure. To resolve this ambiguity, sacculi were
      labeled with deuterated wall peptides. Comparison of the two experimental
      profiles indicated that the sacculus is more than single layered across its
      surface, with about 75 to 80% of its surface single layered and 20 to 25% triple
      layered.

PMID- 1987161
TI  - Bordetella pertussis adenylate cyclase toxin and hemolytic activities require a
      second gene, cyaC, for activation.
AB  - In these studies, the Bordetella pertussis adenylate cyclase toxin-hemolysin
      homology to the Escherichia coli hemolysin is extended with the finding of cyaC,
      a homolog to the E. coli hlyC gene, which is required for the production of a
      functional hemolysin molecule in E. coli. Mutations produced in the chromosome of
      B. pertussis upstream from the structural gene for the adenylate cyclase toxin
      revealed a region which was necessary for toxin and hemolytic activities of the
      molecule. These mutants produced the 216-kDa adenylate cyclase toxin as
      determined by Western blot (immunoblot) analysis. The adenylate cyclase enzymatic
      activities of these mutants were equivalent to that of wild type, but toxin
      activities were less than 1% of that of wild type, and the mutants were
      nonhemolytic on blood agar plates and in in vitro assays. The upstream region
      restored hemolytic activity when returned in trans to the mutant strains. This
      genetic complementation defined a gene which acts in trans to activate the
      adenylate cyclase toxin posttranslationally. Sequence analysis of the upstream
      region defined an open reading frame with homology to the E. coli hlyC gene. In
      contrast to E. coli, this open reading frame is oriented oppositely from the
      adenylate cyclase toxin structural gene.

PMID- 1987163
TI  - A novel extrachromosomally maintained transformation vector for the lignin
      degrading basidiomycete Phanerochaete chrysosporium.
AB  - A stable extrachromosomally maintained transformation vector (pG12-1) for the
      lignin-degrading filamentous fungus Phanerochaete chrysosporium is described. The
      vector is 6.3 kb and contains a Kanr marker, pBR322 ori, and a 2.2-kb fragment
      (ME-1) derived from an endogenous extrachromosomal DNA element of P.
      chrysosporium. Vector pG12-1 was able to transform P. chrysosporium to G418
      resistance and was readily and consistently recoverable from the total DNA of
      transformants via Escherichia coli transformation. Southern blot analyses
      indicated that pG12-1 is maintained at a low copy number in the fungal
      transformants. The vector is demonstrable in the total DNA of individual G418
      resistant basidiospore progeny of the transformants only after amplification by
      polymerase chain reaction. Exonuclease III and dam methylation analyses,
      respectively, indicated that pG12-I undergoes replication in P. chrysosporium and
      that it is maintained extrachromosomally in a circular form. The vector is stably
      maintained in the transformants even after long-term nonselective growth. There
      is no evidence for integration of the vector into the chromosome at any stage.

PMID- 1987164
TI  - Regulation of proline utilization in enteric bacteria: cloning and
      characterization of the Klebsiella put control region.
AB  - Enteric bacteria can grow on proline as the sole nitrogen and carbon source.
      Expression of the proline utilization (put) operon in Klebsiella strains and
      Escherichia coli is responsive to nitrogen regulation. In contrast, Salmonella
      typhimurium cannot activate put operon expression when growing in medium with
      glucose as a carbon source and proline as the sole nitrogen source. To compare
      nitrogen regulatory sites in the control regions of the put operons in these
      three closely related genera, we cloned the Klebsiella put operon onto a plasmid.
      The putA and putP genes were localized on the plasmid by transposon mutagenesis.
      The DNA sequence of the put control region was determined and compared with those
      of the put control regions from S. typhimurium and E. coli. The overall size and
      organization of the put control region were very similar in all three bacteria.
      However, no obvious ntr regulatory sites were found in this region, and
      transcription of the put genes started at the same sites during growth with
      limiting or excess nitrogen. These results strongly suggested that the Klebsiella
      put operon may not be directly regulated by the ntr system.

PMID- 1987165
TI  - The korF region of broad-host-range plasmid RK2 encodes two polypeptides with
      transcriptional repressor activity.
AB  - Broad-host-range IncP plasmid RK2 possesses a series of operons involved in
      plasmid maintenance, whose expression is coordinated by a number of regulators,
      most of which are encoded in the central regulatory korA-korB operon. The
      nucleotide sequence of two new cistrons in this operon, comprising what we have
      previously designated the korF locus located between coordinates 57.0 and 56.0 kb
      on the genome of the IncP alpha plasmid RK2, is presented. The cistrons encode
      polypeptides of 173 and 175 amino acids. Each can repress transcription from the
      promoters for the kfrA (a monocistronic operon which follows the korA-korB
      operon) and trfA (a polycistronic operon encoding a putative single-stranded-DNA
      binding protein as well as the essential plasmid replication protein TrfA)
      operons. In addition, the korF loci allow korB to repress kfrA transcription.
      Both polypeptides contain hydrophobic segments, suggesting that they may be
      membrane associated. KorFI is highly basic protein whose predicted properties are
      similar to those of histone like proteins.

PMID- 1987166
TI  - Characterization of vanadate-dependent NADH oxidation stimulated by Saccharomyces
      cerevisiae plasma membranes.
AB  - Plasma membrane-stimulated vanadate-dependent NADH oxidation has been
      characterized in Saccharomyces cerevisiae. This activity is specific for
      vanadate, because molybdate, a similar metal oxide, did not substitute for
      vanadate in the reaction. Vanadate-dependent plasma membrane-stimulated NADH
      oxidation activity was dependent on the concentrations of vanadate, NADH, and
      NADPH and required functional plasma membranes; no stimulation occurred in the
      presence of boiled membranes or bovine serum albumin. The dependence of membrane
      stimulated vanadate-dependent NADH oxidation was not linearly dependent on added
      membrane protein. The activity was abolished by the superoxide anion scavenger
      superoxide dismutase and was stimulated by paraquat and NADPH. These data are
      consistent with the previously proposed chain reaction for vanadate-dependent
      NADH oxidation. The role of the plasma membrane appears to be to stimulate
      superoxide radical formation, which is coupled to NADH oxidation by vanadate. 51V
      nuclear magnetic resonance studies are consistent with the hypothesis that a
      phosphovanadate anhydride is the stimulatory oxyvanadium species in the phosphate
      buffers used at pHs 5.0 and 7.0. In phosphate buffers, compared with acetate
      buffers, the single vanadate resonance was shifted upfield at both pH 5.0 and pH
      7.0, which is characteristic of the phosphovanadate anhydride. Since the cell
      contains an excess of phosphate to vanadate, the phosphovanadate anhydride may be
      involved in membrane-mediated vanadate-dependent NADH oxidation in vivo.

PMID- 1987167
TI  - Telomeric and dispersed repeat sequences in Candida yeasts and their use in
      strain identification.
AB  - Several different repetitive DNA sequences have been isolated from the pathogenic
      yeast Candida albicans. These include two families of large dispersed repeat
      sequences (Ca3, Ca24) and a short (23-bp) tandemly repeated element (Ca7)
      associated with C. albicans telomeres. In addition, a large subtelomeric repeat
      (WOL17) has been cloned. DNA fragments containing the telomeric repeats are
      highly variable among different C. albicans strains. We have shown that the Ca3
      repeat is relatively more stable and is suitable for use as a species-specific
      and strain-specific probe for C. albicans.

PMID- 1987169
TI  - Peptidoglycan precursor from Fusobacterium nucleatum contains lanthionine.
AB  - Fusobacterium nucleatum was grown in the presence of [14C]UDP. By means of
      sequential precipitation and chromatographic separation of the cytoplasmic
      content, a peptidoglycan [14C]UDP pentapeptide containing lanthionine was
      isolated. This finding indicates that lanthionine is synthesized and incorporated
      as such during the assembly of the peptidoglycan.

PMID- 1987168
TI  - Exopolysaccharide mutants of Rhizobium loti are fully effective on a determinate
      nodulating host but are ineffective on an indeterminate nodulating host.
AB  - By Tn5 mutagenesis of Rhizobium loti PN184 (NZP2037 str-1) and selection for
      nonfluorescence of colonies on Calcofluor agar, eight independently generated
      expolysaccharide (EPS) mutants (three smooth and five rough) were isolated. The
      parent strain, PN184, was found to produce an acidic EPS. This EPS was produced.
      with reduced O acetylation, by the smooth EPS mutants but not by the rough EPS
      mutants. Lipopolysaccharide was isolated from all mutants and was identical to
      that of PN184 as defined by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. All mutants were resistant to lysis by R. loti bacteriophage phi
      2037/1. Cosmids that complemented the mutations in the rough EPS mutants were
      isolated from a pLAFR1 gene library of NZP2037 by complementation of the
      nonfluorescent phenotype. The genes identified were shown to be unlinked and
      located on the chromosome. All mutants were fully effective when inoculated onto
      Lotus pedunculatus, a determinate nodulating host, but were ineffective, inducing
      the formation of very small nodules or tumorlike growths, when inoculated onto
      Leucaena leucocephala, an indeterminate nodulating host. These results, obtained
      in an isogenic Rhizobium background, support suggestions that acidic EPS is
      required for effective nodulation of indeterminate nodulating legumes but is not
      required for effective nodulation of determinate nodulating legumes.

PMID- 1987170
TI  - Transport of nonmetabolizable opines by Agrobacterium tumefaciens.
AB  - We have examined the uptake of [14C]octopine and [14C]nopaline by Agrobacterium
      tumefaciens strains containing the C58 chromosomal background in medium suitable
      for the induction of vir genes. All strains tested could transport both of these
      opines, regardless of the presence or type of Ti plasmid (octopine or nopaline)
      present in the bacterium. The transport of these opines required active cellular
      metabolism. Nonradioactive octopine, nopaline, and arginine competed effectively
      with [14C]octopine and [14C]nopaline for transport into A. tumefaciens A136,
      suggesting that the transport of these opines occurs via an arginine transport
      pathway not encoded by the Ti plasmid.

PMID- 1987172
TI  - Transformation of freshwater and marine caulobacters by electroporation.
AB  - We performed plasmid electrotransformation of Caulobacter crescentus strains and
      obtained up to 3 x 10(8) transformants per micrograms of pKT230. The presence and
      integrity of the paracrystalline protein surface (S) layer influenced
      electroporation; caulobacters lacking the S layer were electrotransformed 10
      times more efficiently than caulobacters possessing the S layers. A procedure
      yielding 1,500 transformants per micrograms of pKT230 was developed for a marine
      caulobacter. Electroporation was used in combination with several genetic
      techniques, including introduction of ligation mixtures, suicide transposon
      mutagenesis, gene replacement, and plasmid electrotransfer from Escherichia coli
      to caulobacters.

PMID- 1987171
TI  - Effect of external pH perturbations on in vivo protein synthesis by the
      acidophilic bacterium Thiobacillus ferrooxidans.
AB  - The response of the obligate acidophilic bacterium Thiobacillus ferrooxidans to
      external pH changes is reported. When T. ferrooxidans cells grown at pH 1.5 were
      shifted to pH 3.5, there were several changes in the general protein synthesis
      pattern, including a large stimulation of the synthesis of a 36-kDa protein
      (p36). The apparent low isoelectric point of p36, its location in the membrane
      fraction, and its cross-reaction with anti-OmpC from Salmonella typhi suggested
      that it may be a porin whose expression is regulated by extracellular pH.

PMID- 1987173
TI  - Demonstration of carbon-carbon bond cleavage of acetyl coenzyme A by using
      isotopic exchange catalyzed by the CO dehydrogenase complex from acetate-grown
      Methanosarcina thermophila.
AB  - The purified nickel-containing CO dehydrogenase complex isolated from
      methanogenic Methanosarcina thermophila grown on acetate is able to catalyze the
      exchange of [1-14C] acetyl-coenzyme A (CoA) (carbonyl group) with 12CO as well as
      the exchange of [3'-32P]CoA with acetyl-CoA. Kinetic parameters for the carbonyl
      exchange have been determined: Km (acetyl-CoA) = 200 microM, Vmax = 15 min-1. CoA
      is a potent inhibitor of this exchange (Ki = 25 microM) and is formed under the
      assay conditions because of a slow but detectable acetyl-CoA hydrolase activity
      of the enzyme. Kinetic parameters for both exchanges are compared with those
      previously determined for the acetyl-CoA synthase/CO dehydrogenase from the
      acetogenic Clostridium thermoaceticum. Collectively, these results provide
      evidence for the postulated role of CO dehydrogenase as the key enzyme for acetyl
      CoA degradation in acetotrophic bacteria.

PMID- 1987174
TI  - Visualization of bacterial flagella by video-enhanced light microscopy.
AB  - We have imaged individual flagellar filaments of Escherichia coli, a motile
      Streptococcus sp., and Rhizobium meliloti by video-enhanced differential
      interference-contrast microscopy (Nomarski DIC) and computer-based image
      processing. This approach has advantages over existing methods in that filaments
      on living cells can be seen over their entire lengths.

PMID- 1987176
TI  - Nephrocalcinosis in homozygous familial hypercholesterolemia: ultrasound and CT
      findings.
AB  - An association between homozygous familial hypercholesterolemia (FH) and
      nephrocalcinosis has not, to our knowledge, been previously reported. Evaluation
      in 10 cases of homozygous FH revealed evidence of nephrocalcinosis in 7 cases.
      Fine, uniform calcifications in the renal papillae were demonstrated by renal
      ultrasound or CT. Renal papillary necrosis was demonstrated by intravenous
      pyelogram in one case. No renal function impairment was noted in these seven
      patients. There was no evidence of hypercalcemia. These findings may have
      implications for the use of a potentially nephrotoxic drug for the treatment of
      this disease--in particular, when an immunosuppressive agent is required
      following liver transplantation.

PMID- 1987175
TI  - MR imaging of anisotropically restricted diffusion of water in the nervous
      system: technical, anatomic, and pathologic considerations.
AB  - The use of MR imaging to image anisotropically restricted diffusion (ARD) of
      water in the nervous system is described. The theoretical basis for the use of
      the pulsed gradient spin echo sequences is outlined, including an estimate of the
      range of cell dimensions that can be studied with this technique. The importance
      of restricted diffusion across myelinated white matter fibre tracts is emphasised
      and the capacity of MR imaging to demonstrate fibre pathways as a function of
      their direction is illustrated. Technical developments that have been implemented
      include 256 x 256 spatial resolution, a wider range of diffusion times Td, and an
      increased range of diffusion sensitivity parameters b. Effects of these are
      illustrated together with the use of gradient moment nulling methods, oblique
      sensitisation, and a smaller set of gradient coils that enable shorter values of
      echo time to be used with the same value of b. The anatomical basis for ARD
      imaging is analysed, and association, commissural, and projection fibre tracts
      are demonstrated in different planes. The published literature on variations of
      the apparent diffusion coefficient from normal is reviewed and examples where
      diffusion weighted images revealed information that was not necessarily apparent
      with conventional sequences are illustrated. These include cases of multiple
      sclerosis, chronic head injury, progressive multifocal leucoencephalopathy,
      cerebrovascular disease, astrocytoma, and probable metastases to the brain.
      Imaging of ARD affords a fascinating conjunction between the microscopic movement
      of water, the properties of myelinated white matter fibres, gross anatomy of the
      brain, and changes of the diffusion of water in disease.

PMID- 1987177
TI  - Evaluation of adrenal masses in oncologic patients: dynamic contrast-enhanced MR
      vs CT.
AB  - The CT examinations, precontrast gradient echo MR images, and fast contrast
      enhanced dynamic MR studies were evaluated in 44 patients with 52 adrenal masses
      and known malignant disease of different origin. Morphologic features (size,
      shape, attenuation, contour, and enhancement) on CT scans, signal intensity on T2
      weighted MR images, and patterns of enhancement on Gd-DTPA enhanced dynamic MR
      studies were analyzed in all patients. With dynamic contrast enhanced studies
      with prolonged imaging up to 15 min after Gd-DTPA, masses with moderate
      enhancement and complete washout after 10 min were considered as adenomas.
      Computed tomography and plain MR had a sensitivity of 0.71 and 0.96, a
      specificity of 0.75 and 0.88, and overall accuracy of 0.56 and 0.71,
      respectively. Simultaneous use of precontrast MR and dynamic contrast enhanced
      studies led to an accurate diagnosis in 88% (sensitivity = 1.0, specificity =
      0.91) and thus should be considered in oncologic patients with undetermined
      adrenal masses.

PMID- 1987178
TI  - MR imaging of adrenal myelolipomas.
AB  - The magnetic resonance (MR) images in six patients with seven adrenal
      myelolipomas are presented. Four lesions involved the right gland, and three the
      left; they ranged from 3 to 12.5 cm in diameter. Magnetic resonance was able to
      image all lesions. Using T1-weighted sequences, three structural patterns were
      observed; (a) homogeneous masses with intensity equal to adjacent fat (three
      cases); (b) heterogeneous masses with fat intensity areas and areas similar to
      renal cortex (two cases); and (c) nodules quite different from fat, hypointense
      to the liver (two cases). On T2-weighted images, myelolipomas were slightly
      hypointense to fat and either hypo- or isointense to the liver. A comparison with
      the results of CT studies was possible in all cases, and good correlation with
      determination of the presence and quantity of fat density tissues within the
      lesions was observed. However, MR imaging did not seem to help in diagnosing
      adrenal myelolipoma in patients with equivocal CT findings, and needle biopsy is
      still needed in difficult cases.

PMID- 1987179
TI  - Acetabular angles and femoral anteversion in dysplastic hips in adults: CT
      investigation.
AB  - Transpelvic CT was used to quantify the relationship between the acetabulum and
      proximal femur in 21 adult patients (33 hips) with congenital hip dysplasia
      (defined by a center edge angle of less than 20 degrees). The anterior and
      posterior acetabular sector angles (AASA and PASA) were measured, as well as the
      degree of acetabular and femoral anteversion. The results demonstrated deficient
      anterior acetabular support (i.e., decreased AASA) in approximately two-thirds of
      the dysplastic hips and reduced posterior support (i.e., decreased PASA) in one
      third. The acetabular anteversion was normal. The femoral anteversion. however,
      was greater than normal in most hip. As important additional information is
      obtained by CT compared with conventional radiography, CT is recommended when
      operative procedures aimed at preventing or postponing osteoarthrosis are
      considered.

PMID- 1987180
TI  - Simulated femoral repositioning with three-dimensional CT.
AB  - Three-dimensional volumetric rendering of CT data has proven to be valuable in
      the evaluation of the hip. Although video loop animation allows review of the
      anatomy from all perspectives, it does not show the functional range of motion of
      the femur in the acetabulum. We have developed a technique termed simulated
      dynamic CT that gives dynamic animated three-dimensional viewing capabilities.
      This technique incorporates static CT data with gait and movement data to produce
      a sequence of dynamic images simulating range of motion. Additionally, this
      technique allows simulation of surgical techniques to visually anticipate the
      results of reduction and traction and potential limitations in subsequent hip
      movement. To assess the potential of this technique, two dysplastic hip patients
      were studied prior to reconstruction. In each case the perspective thus gained
      led to altered surgical management.

PMID- 1987181
TI  - MR imaging of septic sacroiliitis.
AB  - Septic sacroiliitis is difficult to diagnose, causing delayed treatment and
      increased morbidity. The traditional imaging techniques for diagnosis have been
      CT and nuclear medicine. Our purpose was to determine the ability of MR imaging
      to detect septic sacroiliitis, to evaluate the features of septic sacroiliitis
      with MR, and to compare the relative detection rate of MR, CT, and nuclear
      medicine. All patients with a discharge diagnosis of septic sacroiliitis who were
      evaluated by MR imaging of the pelvis were retrospectively evaluated. Five
      patients were collected with six septic sacroiliac joints, which were also
      evaluated with CT, 99mTc-methylene diphosphonate bone scans, and 67Ga-citrate
      scans. Abnormalities consistent with sacroiliitis were seen in all sacroiliac
      joints both prospectively (impression from the initial report) and
      retrospectively on MR. In addition to the nonspecific MR findings of inflammation
      and/or fluid in the sacroiliac joint space, bone marrow of the sacrum and/or
      ilium, and iliopsoas muscle, fluid/inflammation was uniquely identified tracking
      posterior to the iliopsoas muscle in each of these patients with septic
      sacroiliitis. Even in retrospect, a definite diagnosis of sacroiliitis could be
      made in only five of six joints by 67Ga-citrate scans, three of six joints by CT
      scans, and one of six joints by 99mTc-methylene diphosphonate bone scans. These
      results suggest MR imaging may be a sensitive modality in the early diagnosis of
      septic sacroiliitis.

PMID- 1987182
TI  - Cancellous bone structure: analysis of high-resolution CT images with the run
      length method.
AB  - Quantitative computed tomography is extensively used to assess bone density; its
      potential to quantify bone structure, however, remains to be explored. In this
      work we present the modifications of the run-length method necessary to enable an
      analysis of the trabecular bone structure at the distal radius and the distal
      tibia. Furthermore, the close relationship between histomorphometric values and
      the run-length parameters is shown. The procedure may be regarded as a
      noninvasive, reproducible biopsy. For an adequate analysis, high resolution CT
      images are required. To obtain such images, we modified a special purpose CT
      system and achieved a high contrast resolution of 0.25 mm. The procedure was
      applied to groups of normal volunteers and osteoporotic patients, and the results
      are interpreted with the help of simple two- and three-dimensional models of the
      trabecular architecture.

PMID- 1987183
TI  - MR imaging of double chambered left ventricle.
AB  - Double chambered left ventricle is a very rare anomaly within the broader
      category of "subdivision of the left ventricular cavity," which includes the
      relatively more common congenital aneurysms and diverticulae. We report a case of
      an adolescent with double chambered left ventricle that MR clearly delineated,
      resulting in successful surgical correction.

PMID- 1987184
TI  - CT and ultrasound of abdominal hemorrhage in Henoch-Schonlein purpura.

PMID- 1987185
TI  - Computed tomography of primary renal osteosarcoma.
AB  - Primary renal osteosarcoma, a rare malignancy, was diagnosed preoperatively based
      on its unusual imaging features. The CT demonstration of a peripherally located
      renal mass containing ossification suggests the diagnosis of renal osteosarcoma.
      This diagnosis is clinically significant due to the poor prognosis of patients
      with this tumor even when surgically resectable.

PMID- 1987186
TI  - Large Gartner duct cyst associated with a solitary crossed ectopic kidney:
      imaging features.
AB  - A large Gartner duct cyst associated with solitary crossed renal ectopia was
      diagnosed in a young woman presenting with dyspareunia and pelvic pain. Among the
      radiologic imaging modalities used, magnetic resonance imaging and sonography
      were the most helpful in determining the cystic nature of the mass, its
      separation from other pelvic organs, as well as its contiguity with the lateral
      wall of the vagina.

PMID- 1987187
TI  - Hemangioma of the uterine cervix: sonographic and MR diagnosis.
AB  - We present a case of cavernous hemangioma involving the cervix and lower uterine
      segment in a 30-year-old patient. Demonstration of findings on sonography and
      magnetic resonance characteristic for hemangioma led to cancellation of planned
      surgical resection for the clinically suspected uterine neoplasm.

PMID- 1987188
TI  - MR imaging of spindle cell hemangioendothelioma.
AB  - Spindle cell hemangioendothelioma is a slowly progressing vascular tumor of low
      grade malignancy. This neoplasm has been reported in 33 patients but in only one
      patient were osseous lesions seen. The only other description regarding imaging
      of this tumor was CT demonstrating soft tissue masses in the thigh without
      osseous involvement. We present a case of spindle cell hemangioendothelioma in
      which magnetic resonance further defined the radiographic features of this newly
      recognized tumor.

PMID- 1987189
TI  - Sternocleidomastoid tumor of infancy: CT manifestations.
AB  - A case of sternocleidomastoid tumor of infancy in a 1-month-old boy is presented.
      Fine-needle aspiration biopsy can be used to confirm the diagnosis and thereby
      avoid more invasive procedures. Early diagnosis and treatment are important
      factors in achieving a good clinical outcome.

PMID- 1987190
TI  - "Fogging effect" in MR of cerebral infarct.
AB  - In a case of cerebral infarction the lesions were isointense to slightly
      hyperintense in the T2-weighted MR images obtained approximately 2 weeks after
      the onset. Earlier (1 week after onset), they had been markedly hyperintense. The
      probably mechanisms behind this phenomenon, referred to as "MR fogging" are
      discussed.

PMID- 1987191
TI  - Cystic cavernous angioma in an infant: CT features.
AB  - A cavernous angioma with the unusual CT features of a large cyst and a small
      nodule was found in an 8-month-old girl. The cyst contained crystal-clear fluid,
      and a previous hemorrhagic event was histologically confirmed.

PMID- 1987192
TI  - Meningeal metastasis of leiomyosarcoma mimicking meningioma: CT and MR findings.
AB  - A case of leiomyosarcoma metastatic to the meninges is reported. The tumor had
      imaging features typical for meningioma on CT and postcontrast magnetic
      resonance.

PMID- 1987193
TI  - Intracranial amebic abscesses: CT and MR findings.
AB  - The CT and magnetic resonance findings in a case of intracranial amebic abscesses
      are described. Due to increased travel to endemic areas, amebic abscess should
      also be included in the differential diagnosis for patients who live in the
      temperate parts of the world.

PMID- 1987194
TI  - Orbital varix: color flow imaging correlated with CT and MR studies.
AB  - A case of orbital varix is presented in which the lesion is well demonstrated by
      color flow Doppler sonography. Correlation is made with CT and MR studies. We
      believe that color flow sonography should be used as the initial screening test
      in cases of suspected orbital varix.

PMID- 1987195
TI  - Atlantooccipital dislocation: MR demonstration of cord damage.

PMID- 1987196
TI  - Diffuse infiltrating renal metastases presenting as pyonephrosis.

PMID- 1987197
TI  - CT demonstration of a ruptured splenic artery aneurysm.

PMID- 1987198
TI  - Measuring random microscopic motion of water in tissues with MR imaging: a cat
      brain study.
AB  - Cat brain images sensitized to incoherent motion by additional gradient pulses
      were obtained on a 4.7 T magnetic resonance unit equipped with shielded gradient
      coils. The apparent diffusion coefficient of water in gray and white matter was
      accurately determined and imaged from the signal attenuation curve obtained as a
      function of gradient strength. Contrast in calculated diffusion images differed
      from typical T2-weighted contrast. Furthermore, in gray matter and in areas
      containing flowing CSF the attenuation curve was found to be biexponential. These
      results are interpreted in terms of a simple voxel model with microcirculation
      and diffusion contributions.

PMID- 1987199
TI  - A computerized brain atlas: construction, anatomical content, and some
      applications.
AB  - An adjustable computerized atlas of the human brain has been developed, which can
      be adapted to fit individual anatomy. It is primarily intended for positron
      emission tomography (PET) but may also be used for single photon emission CT,
      transmission CT, magnetic resonance imaging, and neuroimaging-based procedures,
      such as stereotactic surgery and radiotherapy. The atlas is based on anatomical
      information obtained from brains fixed in situ soon after death. All structures
      have been drawn in on digitized photos of slices from one cryosectioned brain.
      The definition and classification of the anatomical structures and divisions are
      in agreement with the standard textbooks of anatomy, and the nomenclature is that
      of the Nomina Anatomica of 1965. The boundaries of the cortical cytoarchitectonic
      areas (Brodmann areas) have been determined using information from several
      sources, since three-dimensional literature data on their distribution are
      incomplete, scarce, and partly contradictory. However, no analysis of the
      cytoarchitectonics of the atlas brain itself has been undertaken. At present the
      data base contains three-dimensional representations of the brain surface, the
      ventricular system, the cortical gyri and sulci, as well as the Brodmann
      cytoarchitectonic areas. The major basal ganglia, the brain stem nuclei, the
      lobuli of the vermis, and the cerebellar hemispheres are also included. The
      computerized atlas can be used to improve the quantification and evaluation of
      PET data in several ways. For instance, it can serve as a guide in selecting
      regions of interest. It may also facilitate comparisons of data from different
      individuals or groups of individuals, by applying the inverse atlas
      transformation to PET data volume, thus relating the PET information to the
      anatomy of the reference atlas rather than to the patient's anatomy. Reformatted
      PET data from individuals can thus be averaged, and averages from different
      categories or different functional states of patients can be compared.

PMID- 1987200
TI  - CT appearance of primary CNS lymphoma in patients with acquired immunodeficiency
      syndrome.
AB  - Cranial CT studies of 32 patients with biopsy-proven AIDS-related primary CNS
      lymphoma were reviewed retrospectively. A wide variety of different CT
      appearances were identified. Mass lesions varied in location, size, and number.
      Most lesions were either iso- or hyperdense and all enhanced with contrast
      medium. Several different patterns of enhancement were observed. Mass effect and
      edema were seen in almost all patients. After radiotherapy, most tumors decreased
      in diameter, became hypodense, and no longer enhanced with contrast medium. Edema
      and mass effect decreased or resolved in all but one patient. Postradiotherapy CT
      scans also revealed interval enlargement of the ventricles and cortical sulci.
      This study demonstrates the wide diversity of CT appearances of AIDS-related
      primary CNS lymphoma. The CT findings cannot be used in lieu of biopsy for
      diagnosis of this disorder. The appearance of postradiotherapy CT scans was
      consistent with regressing lymphoma.

PMID- 1987201
TI  - Intracranial meningiomas: correlation between MR imaging and histology in fifty
      patients.
AB  - The magnetic resonance (MR) findings in 50 surgically verified intracranial
      meningiomas were reviewed. An attempt was made to correlate their signal
      intensity on spin echo (SE) T1-weighted, proton density [N(H)], and T2-weighted
      images with the different histologic subtypes. The T1-weighted images were
      nonspecific in differentiating the subtypes of meningiomas. On proton density and
      T2-weighted images, more information was available, but there remained large
      group (46%) of meningiomas that were not classifiable. The average signal
      intensity scores on T1-weighted, proton density, and T2-weighted images in the
      different histologic subtypes were correlated with each other using the Student t
      test. Only one significant correlation (psammomatous-anaplastic) and three almost
      significant correlations (syncytial-transitional or psammomatous and transitional
      psammomatous) were found. Different histologic subtypes may have a different MR
      appearance, but this does not suffice to reach a histologic diagnosis by MR
      imaging.

PMID- 1987202
TI  - Langerhans cell histiocytosis of hypothalamus and optic chiasm: CT and MR
      studies.
AB  - The clinical, CT, and magnetic resonance features of two cases of
      hypothalamic/optic chiasm involvement with Langerhans cell histiocytosis are
      presented. In both cases, the mass was iso- to hyperdense on noncontrast CT with
      uniform postcontrast enhancement, whereas with magnetic resonance (one case) the
      mass remained isointense to brain on both long and short repetition time
      sequences. The pathophysiology of hypothalamic pituitary dysfunction is briefly
      reviewed.

PMID- 1987203
TI  - MR imaging of pineal region neoplasms.
AB  - Twenty-eight patients with tumor of the pineal region underwent magnetic
      resonance (MR) examination. Gadolinium DTPA was given to 13 patients. Histologic
      confirmation was obtained in all patients, including 10 germinomas, 4
      pineocytomas, 4 pineoblastomas, 5 astrocytomas, 2 teratomas, 1 choriocarcinoma, 1
      mixed germ cell tumor, and 1 metastasis from breast carcinoma. Pineal region
      neoplasms have remarkable heterogeneity in both histopathologic and MR
      appearances. Gadolinium DTPA enhanced MR increases the specificity of diagnosing
      pineal region neoplasms. In addition, Gd-DTPA provides better delineation of the
      tumor margin and demonstrates cystic components of the neoplasm. Our approach to
      pineal region neoplasms is to make a decision about whether stereotaxic biopsy or
      surgery should be performed on a certain patient. When a pineal region neoplasm
      is diagnosed as benign, such as a benign teratoma, on the basis of imaging,
      surgery is performed to resect the entire lesion. When a definitive diagnosis is
      not possible, sterotaxic biopsy is performed to obtain histological diagnosis for
      treatment planning. Gadolinium DTPA enhanced MR plays an extremely important role
      in target selection in stereotaxic biopsy of pineal region neoplasms and is also
      useful in the early detection of intracranial seeding. Spinal seeding is
      demonstrated on MR as well, thus alleviating the need for a contrast myelogram.
      Finally, Gd-DTPA enhanced MR can be used to monitor the effects of the various
      treatment modalities employed for pineal region neoplasms.

PMID- 1987204
TI  - "Dural tail sign": a specific MR sign for meningioma?
AB  - Somewhat conflicting reports have appeared about the significance of linear
      meningeal thickening and enhancement adjacent to peripherally located cranial
      mass lesions on contrast enhanced magnetic resonance images. Some authors
      consider this finding nearly diagnostic of meningioma. In an attempt to determine
      the specificity of this so-called tail sign, particularly with respect to
      meningioma, we retrospectively reviewed 16 cases from institutional records. From
      our results, the tail sign appears to be highly suggestive but not specific for
      meningioma.

PMID- 1987205
TI  - N-isopropyl-p-[123I]iodoamphetamine SPECT in MELAS syndrome: comparison with CT
      and MR imaging.
AB  - Regional cerebral perfusion was studied in three patients with the mitochondrial
      encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome,
      using single photon emission computed tomography (SPECT) with N-isopropyl-p
      [123I]iodoamphetamine (IMP). Accumulation of the tracer was relatively decreased
      in the parietooccipital regions and also in the frontotemporal regions after
      stroke-like episodes. However, quantitative regional cerebral blood flow (rCBF)
      measurement showed that rCBF was relatively well preserved even at these sites,
      and a hyperemic state was observed at the sites of normal accumulation. IMP SPECT
      may be useful in the diagnosis and assessment of the progress of the MELAS
      syndrome.

PMID- 1987206
TI  - Spinal angiolipomas: CT and MR aspects.
AB  - Spinal angiolipomas are rare benign tumors containing vascular and mature adipose
      elements. In greater than 90% of the cases they are located in the epidural
      space. The clinical symptomatology is nonspecific, but CT and particularly MR
      studies allow for a precise diagnosis. Computed tomography (four cases in the
      literature plus one explored in our department) showed a hypodense lesion in 80%
      of the cases. In one case the angiolipoma was isodense to the cord. Magnetic
      resonance (three cases in the literature plus two explored in our department)
      showed a more or less homogeneous mass with a signal in T1- and T2-weighted
      images close to that of the subcutaneous fat. The infusion of gadolinium (one
      case in the literature plus one of ours) is helpful as an indicator to the degree
      of vascularization of the angiolipoma.

PMID- 1987207
TI  - CT anatomy of the lingular segmental bronchi.
AB  - Thin-section CT scans were performed in 40 patients to demonstrate the normal
      appearance of the lingular division (LD) bronchus and its segmental and
      subsegmental bronchi and to search out the possible anatomical landmark dividing
      the anterior segment and LD of the left upper lobe. The LD bronchus was
      identified in all patients. The complete branching pattern of the lingular
      segmental and subsegmental bronchi could be traced in 19 (47.5%) patients. Since
      the lower branch of the draining vein of the anterior segment of the left upper
      lobe (V3b) runs horizontally between the anterior segment and the LD of the left
      upper lobe, it is a good landmark dividing the anterior segment and LD of the
      left upper lobe. Familiarity with thin-section CT anatomy of the lingular
      segmental and subsegmental bronchi and surrounding vascular structures is helpful
      in identifying the lingular bronchial tree precisely and localizing a lesion in
      the left upper lobe correctly.

PMID- 1987209
TI  - The recognition of previous abdominal surgery by computed tomography.
AB  - Knowledge regarding previous surgery is important when reporting abdominopelvic
      CT. We have examined 50 consecutive patients undergoing abdominopelvic CT to
      establish whether careful scrutiny of the images can reliably reveal evidence of
      previous surgery. The radiologist performing the CT study inspected the patient's
      abdomen for scars and established their nature by discussion with the patient. A
      second radiologist, unaware of the patient's clinical details, reviewed the CT
      images and predicted whether there had been any previous surgery. These
      predictions proved inaccurate: Only 51% of scars were recognised at this initial
      assessment (63% following retrospective review). Although the absence of major
      organs was reliably reported, even large paramedian scars were missed. Old scars
      were missed more frequently than recent ones. Accurate details of previous
      surgery are necessary when interpreting abdominopelvic CT.

PMID- 1987208
TI  - Primary leiomyosarcoma of the greater omentum: CT findings.
AB  - Three cases of primary leiomyosarcoma arising from the greater omentum are
      described. On CT the tumors were multilobulated, flat, and pancake-like, with
      enhancing solid and multicystic densities. The masses in all cases were located
      in the most anterior part of peritoneal cavity. These CT findings are useful in
      the preoperative diagnosis of omental leiomyosarcoma.

PMID- 1987210
TI  - Percutaneous angioscopy during coronary angioplasty using a steerable
      microangioscope.
AB  - The feasibility of using a flexible, steerable angioscope to perform coronary
      angioscopy before and after percutaneous coronary angioplasty was tested. The
      microangioscope fits through an 8F coronary angioplasty guiding catheter and
      contains a multifiber viewing bundle incorporated into the body of a 4.3F balloon
      catheter with a central lumen for distal flushing and guide-wire passage.
      Angioscopy was performed without complications 45 times in 24 patients, including
      6 patients with stable and 18 with unstable angina. Circumferential visualization
      of the target lesion was successful in 20 (83%) of the 24 patients and improved
      with operator experience. Excellent visualization of the target lesion was
      achieved in 16 (94%) of the last 17 patients. Plaque, thrombus and dissection
      were among the abnormal findings in the 20 patients (4 with stable, 16 with
      unstable angina) in whom circumferential viewing of the target lesion was
      achieved. In four patients with restenosis after angioplasty, the lesion
      morphology was distinctly different from that of lesions in arteries without
      prior angioplasty. In patients with stable angina, no thrombus or dissection was
      seen by angiography or angioscopy before angioplasty. In patients with unstable
      angina, thrombus was detected more frequently by angioscopy than by angiography
      before angioplasty (8 versus 2 of 16) and after (15 versus 2 of 16) angioplasty.
      Intimal dissection was also seen much more frequently by angioscopy than by
      angiography before angioplasty (7 versus 0 of 16) and after angioplasty (16
      versus 7 of 16). It is concluded that high resolution percutaneous coronary
      angioscopy can be performed safely in conjunction with balloon angioplasty.
      Further investigation is needed before this diagnostic tool can be applied
      clinically.

PMID- 1987211
TI  - Evaluation of preload reserve during isometric exercise testing in patients with
      old myocardial infarction: Doppler echocardiographic study.
AB  - To estimate the preload reserve in response to an increase in afterload in
      patients with old myocardial infarction, the relation between the Doppler
      echocardiographic inflow velocity pattern and left ventricular end-diastolic
      pressure was investigated during isometric handgrip exercise testing. The study
      population consisted of 16 normal subjects and 40 patients with old myocardial
      infarction. The 40 patients were subdivided into two groups according to left
      ventricular end-diastolic pressure at rest: group I (22 patients), less than 18
      mm Hg; group II (18 patients), 18 mm Hg or more. At rest, the ratio of peak
      velocity in atrial contraction phase to peak velocity in early diastolic filling
      phase (A/E) was significantly higher in the patients with old myocardial
      infarction than in normal subjects; values in the two subgroups of myocardial
      infarction did not differ significantly. The A/E ratio and left ventricular end
      diastolic pressure increased significantly during exercise in group I.
      Conversely, the change in left ventricular end-diastolic pressure during exercise
      in group II was significantly greater than that in group I, and was associated
      with a decrease in the A/E ratio. Thus, an atrial compensatory mechanism operated
      effectively in response to the increase in afterload in patients with a normal
      left ventricular filling pressure, whereas this compensatory mechanism
      deteriorated in patients with elevated left ventricular filling pressure due to a
      limited preload reserve.

PMID- 1987212
TI  - Noninvasive assessment of intrinsic ventricular load dynamics in dilated
      cardiomyopathy.
AB  - On the basis of hemodynamic theory, a new noninvasive method is developed to
      provide improved insights into the significance of depressed Doppler left
      ventricular ejection variables in patients with dilated cardiomyopathy. The net
      force (F) associated with intraventricular flow throughout ejection can be
      written as: F = A.dv/dt + B.v2, where v is the ejection velocity and A and B are
      variables related to the geometry of the ventricle and its outflow tract.
      Instantaneous levels of this force were calculated in 9 normal subjects and 10
      patients with dilated cardiomyopathy using Doppler, M-mode and two-dimensional
      echocardiography. The maximal ejection force (Fmax) was 47.5 +/- 8.5 kdyn in
      normal subjects and 25.5 +/- 6.2 kdyn in those with dilated cardiomyopathy (p =
      0.0001). Peak local acceleration and outflow velocity were severely depressed in
      those with cardiomyopathy compared with normal subjects (1,260 +/- 129 versus
      2,671 +/- 430 cm/s2 and 71 +/- 14 versus 109 +/- 7 cm/s, respectively; p =
      0.0001). Maximal ejection force was attained very early in ejection. A
      significant linear correlation was found between peak outflow acceleration and
      maximal ejection force (n = 19; r = 0.91, p = 0.0001). At the time of peak
      ejection velocity, the net force had decreased to 64% of its peak value in those
      with cardiomyopathy, whereas in normal subjects, it had decreased to only 84% of
      its peak value (p = 0.008). In normal subjects, the ejection force was positive
      during the first 75% of ejection, but in those with cardiomyopathy, it was
      positive only during the first 54% (p = 0.0003). Once its peak value was
      attained, total left ventricular systolic wall stress declined rapidly during
      ejection in normal subjects (to 33% of its peak value by end-ejection), whereas
      it remained elevated throughout ejection in patients with cardiomyopathy (at 60%
      of its peak value by end-ejection, p = 0.0001 versus normal). The maximal
      ejection force corresponded to a calculated intraventricular peak pressure
      gradient of 9.8 +/- 1.6 mm Hg in normal subjects and 6 +/- 1.2 mm Hg in those
      with cardiomyopathy (p = 0.0001). The average contribution of the intrinsic
      component of the left ventricular systolic load (that is, wall stress associated
      with the ventricular to aortic pressure gradient) to the total myocardial load
      was 9.1% (range 7.3% to 11.2%) in normal subjects and 6.2% (range 3.9% to 7.5%)
      in those with cardiomyopathy (p = 0.0001).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1987213
TI  - Toward a more complete understanding of left ventricular afterload.

PMID- 1987214
TI  - Methodology of head-up tilt testing in patients with unexplained syncope.
AB  - Prolonged 60 degree head-up tilt has been shown to be valuable in the
      investigation of unexplained syncope, diagnosing neurally mediated
      bradycardia/hypotension or malignant vasovagal syndrome. To evaluate the
      methodology of tilt testing, the following were examined: reproducibility of
      results, tilt duration, angle of tilt, method of tilt support and effect of age
      in patients and control subjects. Seventy-one patients with recurrent unexplained
      syncope underwent 60 min of 60 degree tilt; 53 (75%) had an abnormal test with
      vasovagal syncope at 24 +/- 10 min (mean +/- SD). Tilting to 60 degrees resulted
      in an abnormal test in only 2 (7%) of 27 control subjects without cardiovascular
      symptoms (p less than 0.001); and 5 (15%) of 34 patients with syncope and
      documented conduction tissue disease (p less than 0.001). Of 15 youthful
      fainters, 3 (20%) had vasovagal reactions as did 1 (8%) of 12 asymptomatic
      youthful control subjects. These 12 control subjects also underwent tilting with
      a saddle support and 7 (67%) had vasovagal reactions. It is concluded that the
      duration of tilting at 60 degrees should be 45 min (mean time to syncope +2 x SD
      in the 53 patients with abnormal results). Twenty percent of patients with an
      abnormal tilt test may not demonstrate syncope with repeat tilting. Saddle tilt
      testing in unexplained syncope may result in a loss of specificity. Tilting at
      less than 60 degrees results in a loss of sensitivity. Head-up tilt may be less
      useful in youthful subjects with vasovagal syncope than in other subjects.

PMID- 1987215
TI  - Tilt table for the investigation of syncope: there is nothing simple about
      fainting.

PMID- 1987216
TI  - Immediate reproducibility of electrically induced sustained monomorphic
      ventricular tachycardia before and during antiarrhythmic therapy.
AB  - The immediate reproducibility of sustained ventricular tachycardia induction was
      evaluated prospectively during 106 studies performed in 53 patients with clinical
      sustained monomorphic ventricular tachycardia. Programmed electrical stimulation
      was performed twice, using the same protocol during 53 drug-free studies and 53
      subsequent studies on antiarrhythmic therapy. Sustained monomorphic ventricular
      tachycardia was reproduced in 104 (98%) of the 106 studies. There was no
      significant difference in the incidence of reproducible tachycardia in the drug
      free state compared with that observed during treatment with different classes of
      antiarrhythmic drugs. An increase in the number of extrastimuli was required to
      reinitiate the tachycardia in 9 (11%) of 83 studies in which single or double
      extrastimuli were initially required to induce the tachycardia. In 39 (37%) of
      104 studies with reproducible tachycardia induction, the two tachycardias
      significantly differed in electrocardiographic (ECG) configuration and cycle
      length. These observations suggest that the overall reproducibility of
      ventricular tachycardia induction is sufficiently high to provide a reliable
      marker for evaluating the efficacy of therapeutic interventions. However,
      specific tachycardia characteristics such as cycle length and ECG configuration
      are more variable even within the same study and may be less useful in assessing
      the effects of subsequent interventions.

PMID- 1987217
TI  - Cardiac excitability, the electrophysiologic matrix and electrically induced
      ventricular arrhythmias: order and reproducibility in seeming electrophysiologic
      chaos.

PMID- 1987218
TI  - Differences in QRS configuration during unipolar pacing from adjacent sites:
      implications for the spatial resolution of pace-mapping.
AB  - To examine the spatial resolution of unipolar pace-mapping, 12 lead
      electrocardiograms (ECGs) recorded during pacing from each of the poles of a
      quadripolar catheter (5 mm interelectrode distance) were examined. Unipolar
      pacing was performed from each of the poles at late diastolic threshold, twice
      threshold and 10 mA at a cycle length of 500 ms. In 15 patients, pacing was
      performed at the right ventricular apex and in 14 at various left ventricular
      sites. Pacing from the distal catheter pole at threshold (index ECG) was used to
      simulate the site of origin of ventricular tachycardia, and all other ECGs were
      compared with the index ECG. Electrocardiograms were evaluated by two independent
      observers for 1) minor configuration differences (notch, new small component,
      change in the amplitude of individual components or change in QRS shape); 2)
      major differences in configuration (new large component, marked change in the
      amplitude of an existing component or two minor changes); and 3) peak to peak
      changes in amplitude. Minor differences in configuration were seen in a mean 2.4
      +/- 1.9, 4.6 +/- 2.4 and 4.4 +/- 2.9 leads during pacing at 5, 10 and 15 mm from
      the distal electrode (index site). Major differences in configuration were seen
      in a mean of 0.3 +/- 0.5, 2.1 +/- 2.1 and 3.7 +/- 2.3 leads during pacing at 5,
      10 and 15 mm from the index site. Differences in amplitude were seen in a mean of
      3.1 +/- 2.2, 5.6 +/- 2.5 and 6.8 +/- 3.0 leads per ECG during pacing at 5, 10 and
      15 mm from the index ECG pacing site, respectively.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1987219
TI  - Lack of prognostic value of syncope in patients with Wolff-Parkinson-White
      syndrome.
AB  - Syncope in patients with Wolff-Parkinson-White syndrome may be considered a
      premonitory event heralding the future development of sudden death. Therefore,
      the clinical and electrophysiologic data of 101 patients with Wolff-Parkinson
      White syndrome referred for invasive evaluation of known arrhythmias were
      reviewed to assess the incidence and clinical relevance of syncope. Thirty-six
      patients reported the occurrence of one or more syncopal episodes (group 1) and
      65 patients had no syncope (group 2). These two groups did not differ
      significantly with regard to age, gender, incidence and characteristics of
      arrhythmia, clinical history, frequency of arrhythmic events and presence of
      associated cardiac disease. There were 10 patients in group 1 and 12 in group 2
      who had ventricular fibrillation. There were no statistical differences between
      the two groups with respect to the effective refractory period of the right
      atrium, atrioventricular node, accessory pathway and right ventricle.
      Furthermore, no differences between the two groups were noted with respect to
      cycle length of circus movement tachycardia, mean heart rate during atrial
      fibrillation, and minimum RR interval during atrial fibrillation. In addition,
      the accessory pathway location was not significantly different between group 1
      and group 2. The occurrence of syncope could not be predicted from any
      electrophysiologic finding and this symptom had a low sensitivity and specificity
      for recognition of dangerous rapid heart rates. Furthermore, the prognostic value
      of syncope was less accurate and predictive than the shortest RR interval during
      atrial fibrillation and the anterograde effective refractory period of the
      accessory pathway for aborted sudden death occurrence.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1987220
TI  - Syncope and sudden death in the Wolff-Parkinson-White syndrome.

PMID- 1987221
TI  - Longitudinal dissociation of atrioventricular accessory pathways.
AB  - Unusual properties of atrioventricular (AV) accessory pathways were found during
      electrophysiologic investigations in four patients (three men and one woman).
      Anterograde longitudinal dissociation of the accessory pathway was observed in
      two patients and retrograde longitudinal dissociation in two others. Two patients
      had an accessory pathway with a slow conduction time, one in anterograde
      direction and one in retrograde direction. These observations further expand our
      knowledge of the spectrum of electrophysiologic properties of accessory AV
      pathways.

PMID- 1987222
TI  - Tricuspid valve disease with significant tricuspid insufficiency in the fetus:
      diagnosis and outcome.
AB  - The echocardiographic studies and clinical course of 27 fetuses (mean gestational
      age 26.9 weeks) diagnosed in utero with tricuspid valve disease and significant
      tricuspid regurgitation were reviewed. The diagnosis of Ebstein's anomaly was
      made in 17 of the fetuses, 7 had tricuspid valve dysplasia with poorly developed
      but normally attached leaflets and 2 had an unguarded tricuspid valve orifice
      with little or no identifiable tricuspid tissue. One fetus was excluded from data
      analysis because a more complex heart lesion was documented at autopsy. All
      fetuses had massive right atrial dilation and most who were serially studied had
      progressive right-sided cardiomegaly. Hydrops fetalis was found in six cases and
      atrial flutter in five. Associated cardiac lesions included pulmonary stenosis in
      five cases and pulmonary atresia in six. Four fetuses with normal forward
      pulmonary artery flow at the initial examination were found at subsequent study
      to have retrograde pulmonary artery and ductal flow in association with the
      development of pulmonary stenosis (n = 1) and pulmonary atresia (n = 3). On
      review of the clinical course of the 23 fetuses (excluding 3 with elective
      abortion), 48% of the fetuses died in utero and 35% who were liveborn died
      despite vigorous medical and, when necessary, surgical management, many of whom
      had severe congestive heart failure. Of the four infants who survived the
      neonatal period, three had a benign neonatal course, all of whom were diagnosed
      with mild to moderate Ebstein's anomaly; only one had pulmonary outflow
      obstruction. An additional finding at autopsy was significant lung hypoplasia
      documented in 10 of 19 autopsy reports.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1987223
TI  - Electrophysiologic findings after Fontan repair of functional single ventricle.
AB  - Cardiac arrhythmias are well recognized sequelae of the Fontan operation for
      complex congenital anomalies. In this study the electrophysiologic effects of the
      Fontan procedure were evaluated in 30 patients who underwent cardiac
      catheterization with electrophysiologic study 1.9 +/- 1.3 years (mean +/- SD)
      after modified Fontan repair for functional single ventricle. Abnormalities of
      sinus node or ectopic pacemaker automaticity were detected in 50% (15 patients)
      by determination of a prolonged corrected sinus node or pacemaker recovery time.
      Total sinoatrial conduction time was prolonged in 50% of the patients with normal
      sinus rhythm. Sinus node or ectopic atrial pacemaker function was entirely normal
      in only 43% of patients. The predominant atrial rhythm was normal sinus in 70%
      and ectopic atrial or junctional in 30%. Abnormalities of atrial effective and
      functional refractory periods were noted in 43% of patients and were most
      pronounced at faster paced cycle lengths. Atrial endocardial catheter mapping
      revealed intraatrial conduction delays between adjacent sites in 76% of the
      patients tested and in eight of nine patients with inducible intraatrial reentry.
      Programmed atrial stimulation induced nonsustained supraventricular arrhythmias
      in 10% of the 30 patients and sustained arrhythmias in 27%. Intraatrial reentry
      was the most common inducible arrhythmia and was present in seven of the eight
      patients with sustained and two of the three patients with nonsustained atrial
      arrhythmias. Atrioventricular conduction abnormalities were noted in 10% (three
      patients). No patient had inducible ventricular arrhythmias with programmed
      ventricular stimulation. The electrophysiologic findings after Fontan repair
      include abnormal sinus node function, prolonged atrial refractoriness, delayed
      intraatrial conduction and inducible atrial arrhythmias.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1987224
TI  - Late noninvasive evaluation of cardiac performance in mildly symptomatic older
      patients with Ebstein's anomaly of tricuspid valve: role of radionuclide imaging.
AB  - Ten patients 8 to 54 years of age with isolated Ebstein's anomaly of the
      tricuspid valve were evaluated by electrocardiography, maximal exercise treadmill
      testing, 24 h electrocardiographic (ECG) monitoring, echocardiography and rest
      radionuclide imaging of the left ventricle. The patients presented after the 1st
      year of life and had not undergone surgical intervention. All except one were in
      functional class II. No patient had preexcitation on the surface ECG, but
      abnormal tachyarrhythmias or bradyarrhythmias were seen in five patients on 24 h
      ECG monitoring. Subnormal exercise performance was observed in five patients.
      Echocardiography demonstrated typical variable tricuspid valve displacement and
      paradoxic interventricular septal motion. Left ventricular end-diastolic
      dimensions were normal in all patients, but posterior wall motion was reduced in
      two. Moderate to severe tricuspid regurgitation with a Doppler jet velocity less
      than 2.5 m/s was demonstrated in eight patients. Left ventricular radionuclide
      scintigraphy revealed a subnormal ejection fraction (less than 50%) in 5 of 10
      patients; these 5 had previously shown suboptimal exercise performance. The two
      youngest patients (less than 15 years) had no arrhythmia, normal exercise
      performance and normal left ventricular ejection fraction. There was no
      correlation between the degree of tricuspid valve displacement or regurgitation
      and the presence of rhythm disturbance, exercise performance or radionuclide left
      ventricular function. Late evaluation of patients with Ebstein's anomaly may
      demonstrate significant unsuspected abnormalities in cardiac rhythm, exercise
      performance and left ventricular function. Radionuclide scintigraphy is a useful
      noninvasive technique for assessing left ventricular dysfunction in these
      patients.

PMID- 1987225
TI  - In-hospital mortality after balloon aortic valvuloplasty: frequency and
      associated factors.
AB  - Percutaneous balloon aortic valvuloplasty has been accompanied by significant
      early periprocedural morbidity and mortality. Identification of factors
      associated with increased mortality might allow for improved selection of
      patients. The Mansfield Scientific Balloon Aortic Valvuloplasty Registry was
      analyzed to identify the frequency of in-hospital death and the factors
      associated with it. Of 492 patients undergoing the procedure, 37 (7.5%) died
      during the hospital stay in which valvuloplasty was performed. Twenty-four of
      these patients died within the first 24 h and the remainder died within 7 days
      after the procedure. There were significant differences in baseline clinical and
      hemodynamic characteristics as well as procedural and postprocedural variables
      between patients dying and those surviving the in-hospital period. Multivariate
      analysis identified four factors associated with increased mortality: 1) the
      occurrence of a procedure-related complication, 2) a lower initial left
      ventricular systolic pressure, 3) a smaller final aortic valve area, and 4) a
      lower baseline cardiac output. Thus, baseline hemodynamic, procedural and
      postprocedural variables and complications can be identified that are associated
      with increased mortality.

PMID- 1987226
TI  - Predictors of long-term survival after percutaneous aortic valvuloplasty: report
      of the Mansfield Scientific Balloon Aortic Valvuloplasty Registry.
AB  - Percutaneous balloon aortic valvuloplasty was used to prospectively treat 492
      elderly, symptomatic, nonsurgical patients suffering from severe aortic stenosis
      in 27 centers in North America and Europe. At 1 year the overall survival rate
      was 64% and the event-free survival rate (survival free of valve replacement or
      repeat valvuloplasty) was 43%. Clinical, catheterization and procedural variables
      were assessed to define prognostic variables. Univariate analysis revealed that
      patients who survived had a lesser frequency of previous myocardial infarction
      (2% versus 6%, p less than 0.005), lower incidence of severe ventricular
      dysfunction (22% versus 48%, p less than 0.001) and lower incidence of symptoms
      of heart failure (60% versus 75%, p less than 0.02). History of angina (56%
      versus 45%, p = NS) and syncope (23% versus 16%, p = NS) were similar for both
      groups. Values obtained at cardiac catheterization that differed in survivors and
      nonsurvivors included lower pulmonary artery systolic pressure (43 +/- 1 versus
      54 +/- 2 mm Hg, p less than 0.001), lower mean pulmonary artery pressure (28 +/-
      1.0 versus 36 +/- 1.0 mm Hg, p less than 0.001) and larger initial valve area
      (0.52 +/- 0.01 versus 0.47 +/- 0.02 cm2, p = 0.006). Discriminate function
      analysis was performed to identify variables that independently predicted
      improved probability of survival. Eight variables were significantly and
      independently predictive. These included age, initial cardiac output, initial
      left ventricular systolic pressures, initial left ventricular end-diastolic
      pressures, presence of coronary artery disease, New York Heart Association
      dyspnea classification, number of balloon inflations and final valve
      area.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1987227
TI  - Ventricular load optimization by unloading therapy in patients with heart
      failure.
AB  - The effects of unloading a depressed heart were assessed in terms of optimal
      coupling between the ventricle and arterial system. To assess the effects of
      preload on ventricular load coupling, preload was reduced with a lower body
      negative pressure of -20 mm Hg. Nitroprusside was used to evaluate the effects of
      afterload on the coupling under the condition that preload reduction was
      comparable to that with lower body negative pressure. In 13 patients with heart
      failure (ejection fraction 32 +/- 3%, mean +/- SE), direct arterial pressure was
      simultaneously recorded with the left ventricular echocardiogram as the pressure
      was elevated by phenylephrine. Left ventricular contractile properties were
      defined by the slope (Ees) of the end-systolic pressure-volume relation. The
      effective arterial elastance (Ea) was expressed by the slope of the end-systolic
      pressure-stroke volume relation. Left ventricular external work, end-systolic
      potential energy and work efficiency, defined as external work per pressure
      volume area (external work + potential energy), were determined. Baseline
      ventricular load coupling in these patients was characterized by an increase in
      the ratio of arterial elastance to ventricular elastance (Ea/Ees) (1.96 +/-
      0.31). This ratio decreased significantly, to 1.45 +/- 0.22, with nitroprusside,
      and increased to 2.37 +/- 0.34 with lower body negative pressure. Therefore, end
      systolic potential energy was decreased by nitroprusside but was unaltered by
      lower body negative pressure while external work was comparably decreased by both
      manipulations, indicating that work efficiency was significantly augmented with
      nitroprusside but declined with lower body negative pressure.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1987228
TI  - Cardiovascular and hormonal effects of calcitonin gene-related peptide in
      congestive heart failure.
AB  - The effects of infusing human alpha-calcitonin gene-related peptide were studied
      in eight patients with congestive heart failure, five normal rabbits and five
      rabbits with adriamycin-induced cardiomyopathy. In patients with heart failure,
      calcitonin gene-related peptide caused a dose-dependent increase in cardiac
      output and decrease in pulmonary and systemic vascular resistance and pulmonary
      artery pressure. The systemic blood pressure and right atrial and pulmonary wedge
      pressures decreased only at the highest infusion rate (16 ng/kg per min). Heart
      rate remained unchanged. Plasma epinephrine increased (p less than 0.05), whereas
      aldosterone, atrial natriuretic peptide and prolactin concentrations decreased (p
      less than 0.05). Plasma norepinephrine, renin activity, cortisol and growth
      hormone concentrations remained unchanged. In both groups of rabbits, the drug
      decreased blood pressure and increased cardiac output and heart rate. There was a
      significant increase in renal blood flow (p less than 0.05). The peptide did not
      affect the contraction amplitude of human and rabbit ventricular myocytes. These
      findings suggest that calcitonin gene-related peptide is a vasodilator in the
      rabbit and humans with little direct effect on ventricular myocardium. This
      peptide may be useful in some forms of heart failure.

PMID- 1987230
TI  - Influence of incremental changes in heart rate on mitral flow velocity:
      assessment in lightly sedated, conscious dogs.
AB  - To determine the effect of increasing heart rate on mitral flow velocity
      variables, the time constant of left ventricular isovolumic relaxation and the
      transmitral pressure gradient, 16 lightly sedated, conscious dogs were studied
      with Doppler echocardiography during incremental right atrial pacing (n = 16) or
      the administration of atropine (n = 8) or isoproterenol (n = 8). With increasing
      heart rate, similar changes were seen with all three interventions and included:
      1) mitral flow velocity in early diastole and the early diastolic transmitral
      pressure gradient either changed minimally or did not change; 2) mitral flow
      velocity at the start of and as a result of atrial contraction progressively
      increased; 3) the "absolute" increase in mitral flow velocity and transmitral
      pressure gradient at atrial contraction demonstrated a biphasic response,
      initially decreasing as heart rate increased, but then increasing again when
      atrial contraction occurred in close proximity (less than 70 ms) to mitral valve
      opening; 3) mitral flow velocity at atrial contraction did not exceed mitral flow
      velocity in early diastole until atrial contraction was within 70 ms of mitral
      valve opening and the two velocity peaks were nearly fused; and 4) the largest
      transmitral pressure gradient and mitral flow velocity occurred at the fastest
      heart rates, when left atrial contraction preceded mitral valve opening. Major
      differences among methods included: 1) variable changes in PR interval (+14.2 +-
      8.9 ms with atrial pacing versus -74 +/- 26 ms with isoproterenol at peak heart
      rate compared with baseline); 2) variable changes in the speed of left
      ventricular relaxation (-2.8 +/- 2.8 ms with pacing versus -7.6 +/- 2.4 ms with
      isoproterenol at peak rate); and 3) the heart rate at which equalization of
      mitral flow velocity in early diastole and mitral flow velocity at atrial
      contraction velocity occurred (128 +/- 12 beats/min with pacing versus 185 +/- 19
      beats/min with isoproterenol). These results show that regardless of method,
      qualitatively similar changes in mitral flow velocity and transmitral pressure
      gradient occur as heart rate increases. However, for any given heart rate, mitral
      flow velocity variables and late diastolic pressure gradient can be markedly
      different, depending on whether atrial pacing, withdrawal of parasympathetic tone
      or sympathetic stimulation is the cause of the increase in heart rate. These
      differences among methods appear most related to their effect on PR interval and
      to a lesser extent the rate of letf ventricular isovolumic relaxation.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 1987229
TI  - Clinical and angiographic determinants of primary coronary angioplasty success. M
      HEART Investigators.
AB  - Clinical and anatomic determinants of the initial success of percutaneous
      transluminal coronary angioplasty were prospectively evaluated in 826 patients
      enrolled in the Multi-Hospital Eastern Atlantic Restenosis Trial (M-HEART). The
      639 men and 187 women ranged in age from 31 to 85 years. Successful angioplasty
      (residual stenosis less than 50% and no major complications) was achieved in 886
      (88.6%) of 1,000 lesions. Success rates were uniform among the eight individual
      centers. Outcome was not influenced by gender, age or other clinical features,
      including severity and duration of angina, prior myocardial infarction, rest
      pain, transient ST segment elevation, history of smoking or diabetes. In
      contrast, procedural outcome was significantly associated with lesion-specific
      angiographic factors. Stenoses 60% to 74%, 75% to 89%, 90% to 99% and 100% were
      associated with success rates of 96%, 90%, 84% and 69%, respectively (p less than
      0.001). Angioplasty was less successful in calcified than in noncalcified lesions
      (82% versus 90%, p less than 0.01), in thrombotic than in nonthrombotic lesions
      (82% versus 90%, p less than 0.05) and in lesions in the right coronary artery
      than in other vessels (84% versus 90%, p less than 0.01). Outcome was not related
      to other anatomic variables, including lesion location (proximal versus distal),
      vessel size, eccentricity, stenosis length or translesional gradient. By
      multivariate logistic regression, preangioplasty percent stenosis, right coronary
      artery location and lesion calcification were demonstrated to be significant
      independent predictors of angioplasty success. Alternative clinical and
      angiographic variables did not contribute to this regression model.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1987231
TI  - The increasing complexity of assessing diastolic function from ventricular
      filling dynamics.

PMID- 1987232
TI  - Experimental pericardial effusion: relation of abnormal respiratory variation in
      mitral flow velocity to hemodynamics and diastolic right heart collapse.
AB  - Pericardial effusion is associated with an abnormal increase in respiratory
      variation in mitral flow velocity. However, the relation of the changes in flow
      velocity to pericardial pressure, hemodynamics and two-dimensional
      echocardiographic findings is not established. Therefore, 11 sedated dogs with
      extensive hemodynamic instrumentation were studied with two-dimensional and
      Doppler echocardiography during four stages of progressively larger pericardial
      effusion. During all stages of effusion, respiratory variation in peak mitral
      flow velocity in early diastole and left ventricular isovolumetric relaxation
      time was increased compared with baseline (p less than 0.05). This increase was
      seen at the earliest stage of effusion (mean pericardial pressure 4.2 +/- 1.4
      versus -0.8 +/- 0.9 mm Hg at baseline, p less than 0.05), and preceded the
      appearance of unequivocal diastolic right heart collapse in every dog. Maximal
      respiratory variation coincided with the appearance of right atrial collapse
      (mean pericardial pressure 7.1 +/- 2.4 mm Hg; mean inspiratory decrease in aortic
      pressure 9.5 +/- 2.6 mm Hg; mean aortic pressure 88.2 +/- 15.2 versus 102.2 +/-
      11.2 mm Hg at baseline, p less than 0.05; and cardiac output 3.8 +/- 1.2 versus
      5.5 +/- 1.3 liters/min at baseline, p less than 0.05), but did not increase at
      stages associated with more severe hemodynamic compromise. In addition, the
      respiratory changes in peak mitral flow velocity in early diastole were
      associated with simultaneous changes in the diastolic transmitral pressure
      gradient. It is concluded that in this model of acute pericardial effusion 1)
      increased respiratory variation in early diastolic mitral flow velocity, peak
      mitral flow velocity in early diastole and left ventricular isovolumetric
      relaxation time occurs almost immediately as pericardial pressure increases and
      persists at all stages of increasing pericardial effusion; 2) the abnormal
      respiratory variation occurs before equalization of intracardiac pressures and
      before the onset of unequivocal right heart collapse; 3) the respiratory
      variation occurs as a result of changes in the diastolic transmitral pressure
      gradient; and 4) the magnitude of the respiratory change is not necessarily
      predictive of pericardial pressure or severity of hemodynamic compromise,
      especially at the more severe stages of pericardial effusion.

PMID- 1987233
TI  - The effects of pericardial effusion on respiratory variations in hemodynamics and
      ventricular function.

PMID- 1987234
TI  - A quantitative index of regional blood flow in canine myocardium derived
      noninvasively with N-13 ammonia and dynamic positron emission tomography.
AB  - To derive a quantitative index of regional myocardial blood flow, the arterial
      input function of the flow tracer N-13 ammonia and the regional myocardial N-13
      activity concentrations were noninvasively determined in 29 experiments in eight
      dogs. N-13 ammonia was administered intravenously and cross-sectional images were
      acquired dynamically using an ECAT III positron emission tomograph with an
      effective in-plane resolution of 13.46 mm full-width half-maximum. Time-activity
      curves were derived from the serial images by assigning regions of interest to
      the left ventricular myocardium and left ventricular blood pool. Tracer net
      extractions were estimated from the myocardial time-activity concentrations at
      various times after tracer injection and the integral of the arterial input
      function. Myocardial blood flow was altered by intravenous dipyridamole,
      morphine, propranolol and partial or complete occlusion of the left anterior
      descending coronary artery, and ranged from 9 to 860 ml/min per 100 g. Estimates
      of tracer net extractions were most accurate when determined from the myocardial
      N-13 activity concentrations at 60 s divided by the integral of the arterial
      input function to that time. These estimates correlated with regional myocardial
      blood flows determined independently by the microsphere technique by y = x (1 -
      0.64(e-114/x); SEE = 22.9; r = 0.94). First pass extraction fractions of N-13
      ammonia determined noninvasively with this approach declined with higher flows in
      a nonlinear fashion and were similar to those determined invasively by direct
      intracoronary N-13 ammonia injections. The findings indicate that an accurate
      index of regional myocardial blood flow can be obtained noninvasively by high
      temporal sampling of arterial and myocardial tracer activity concentrations with
      positron emission tomography. They also provide a basis for the in vivo
      application of tracer kinetic principles to derive quantitatively and
      noninvasively regional rates of functional processes in human myocardium.

PMID- 1987235
TI  - Quantitative determination of regional myocardial blood flow: can it be
      accurately measured noninvasively?

PMID- 1987236
TI  - The flail mitral valve: echocardiographic findings by precordial and
      transesophageal imaging and Doppler color flow mapping.
AB  - To determine the echocardiographic and Doppler characteristics of mitral
      regurgitation associated with a flail mitral valve, precordial and
      transesophageal echocardiography with pulsed wave and Doppler color flow mapping
      was performed in 17 patients with a flail mitral valve leaflet due to ruptured
      chordae tendineae (Group I) and 22 patients with moderate or severe mitral
      regurgitation due to other causes (Group II). Echocardiograms were performed
      before or during cardiac surgery; cardiac catheterization was also performed in
      28 patients (72%). Mitral valve disease was confirmed at cardiac surgery in all
      patients. By echocardiography, the presence of a flail mitral valve leaflet was
      defined by the presence of abnormal mitral leaflet coaptation or ruptured
      chordae. Using these criteria, transesophageal imaging showed a trend toward
      greater sensitivity and specificity than precordial imaging in the diagnosis of
      flail mitral valve leaflet. By Doppler color flow mapping, a flail mitral valve
      leaflet was also characterized by an eccentric, peripheral, circular mitral
      regurgitant jet that closely adhered to the walls of the left atrium. The
      direction of flow of the eccentric jet in the left atrium distinguished a flail
      anterior from a flail posterior leaflet. By transesophageal echocardiography with
      Doppler color flow mapping, the ratio of mitral regurgitant jet arc length to
      radius of curvature was significantly higher in Group I than Group II patients
      (5.0 +/- 2.3 versus 0.7 +/- 0.6, p less than 0.001); all of the Group I patients
      and none of the Group II patients had a ratio greater than 2.5.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1987237
TI  - Historical vignette celebrating the 30th anniversary of diagnostic ambulatory
      electrocardiographic monitoring and data reduction systems.
AB  - The ambulatory electrocardiographic (ECG) monitor is a device developed
      approximately 30 years ago to detect, locate and document hemodynamic
      insufficiency states in target organs with compromised regional arterial
      circulations. These insufficiency states are usually silent until they are
      suddenly precipitated by secondary remote, hemodynamically significant cardiac
      arrhythmias, hypotensive states caused by internal hemorrhage or reduced cardiac
      output including cardiogenic shock. Insufficiency events cause serious regional
      dysfunction, resulting in transitory or permanent damage of the remote target
      organs (brain, heart, splanchnic and renal) often causing paralytic ileus,
      gangrene of the gut or rectum, myocardial infarction or cerebral stroke.
      Comprehensive experimental studies conducted in the author's laboratory over a
      period of years (1946-1971) proved that such remote ischemic states are often
      recurrent and can cause serious, irreparable damage, but whenever the cause of
      the regional ischemic state was treated promptly it could reverse the
      insufficiency state. Practical ambulatory ECG diagnostic monitors and data
      reduction systems were developed to diagnose these elusive precipitating
      pathophysiologic events that might coincide with the patient's symptoms and thus
      determine the most appropriate preventive therapy.

PMID- 1987238
TI  - Outcome probabilities and life history after surgical mitral commissurotomy:
      implications for balloon commissurotomy.
AB  - From 1967 to 1988, 339 patients with mitral stenosis underwent surgical
      commissurotomy, 103 with a closed and 236 with an open technique. The 1 month and
      1, 5, 10 and 20 year overall survival rate was 99.7%, 99%, 95%, 87% and 59%,
      respectively, and the technique (open versus closed) was not a risk factor.
      Technique was also not a risk factor for a second mitral commissurotomy,
      subsequent mitral valve replacement, thromboembolism or poor functional status.
      Risk factors were older age at commissurotomy, black race, higher pulmonary
      vascular resistance, mitral leaflet calcification, left ventricular enlargement
      and postcommissurotomy mitral incompetence. The closed technique was a risk
      factor for mitral incompetence immediately after commissurotomy, but important
      incompetence developed in only 2 of the 103 patients undergoing closed
      commissurotomy. Mitral valve replacement was not required within 10 years in 78%
      of patients and within 20 years in 47%. Despite some increased prevalence of
      postcommissurotomy mitral incompetence and particularly in view of the
      considerable long-term likelihood of mitral valve replacement, initial therapy
      for most patients with mitral stenosis should probably be surgical closed (or
      percutaneous balloon) mitral commissurotomy. The equations developed in the
      present study can be used to predict and compare outcome probability after
      percutaneous balloon commissurotomy with that after surgical commissurotomy and
      to compare these with outcome probability after mitral valve replacement.

PMID- 1987239
TI  - Spontaneous alterations in coronary blood flow velocity before and after coronary
      angioplasty in patients with severe angina.
AB  - Cyclic coronary artery flow variations with a spontaneous decline in coronary
      blood flow to very low levels have been documented in stenosed canine coronary
      arteries with endothelial injury. These flow variations are associated with
      transient platelet aggregation and dislodgment and the release of selected
      mediators, including thromboxane A2 and serotonin. However, cyclic or spontaneous
      flow variations have not been demonstrated in stenosed coronary arteries in
      humans. In this study, the hypothesis was tested that spontaneous coronary blood
      flow velocity variations occur in some patients with stenosed coronary arteries
      before or after coronary artery angioplasty. Thus, 13 patients with severe and
      limiting angina underwent intracoronary pulsed Doppler velocimetry of their
      dilated artery immediately before and after percutaneous transluminal coronary
      angioplasty, whereas 9 control patients underwent velocimetry of an
      angiographically normal coronary artery. A 3F catheter with a 20 MHz Doppler
      crystal was positioned to achieve a maximal stable signal, and the flow velocity
      signal was recorded continuously for 20 min. Spontaneous flow velocity variations
      (greater than or equal to 38% change in Doppler frequency shift with wide
      morphologic changes) were present in 3 of the 13 patients tested. Spontaneous
      flow velocity variations occurred before angioplasty in one patient, after
      angioplasty in another and both before and after angioplasty in a third. In
      addition, 2 of the 13 patients, 1 with spontaneous coronary artery flow velocity
      variations before angioplasty, had frank vasospasm in an adjacent area just
      distal to the area of coronary dilation immediately after balloon inflation.
      These data establish that spontaneous coronary artery flow velocity variations
      occur in some patients with severe and limiting angina before and after coronary
      angioplasty. These variations may be related to platelet aggregation or coronary
      vasoconstriction, or both, at sites of endothelial injury resulting from plaque
      fissuring or ulceration and endothelial and medial injury occurring during
      coronary angioplasty.

PMID- 1987240
TI  - Elevated plasma beta-endorphin levels in patients with congestive heart failure.
AB  - Recent experimental studies show that the opioid system is important to the
      pathophysiology of cardiovascular impairment in congestive heart failure. Plasma
      beta-endorphin levels were measured in 37 patients with congestive heart failure
      and compared with those of 21 age- and gender-matched normal subjects. The
      relation of plasma beta-endorphin levels and cardiac function at rest and
      exercise capacity was assessed in 17 of the patients with dilated cardiomyopathy.
      Exercise capacity was determined by symptom-limited maximal treadmill exercise
      with expired gas analysis. Plasma beta-endorphin levels were elevated and
      correlated with the patients' New York Heart Association functional cardiac
      status (control: 14.0 +/- 4.4 pg/ml; class II: 17.9 +/- 3.6 pg/ml; class III:
      28.3 +/- 8.8 pg/ml; class IV: 46.7 +/- 14.6 pg/ml, mean +/- SD). No relation was
      found between plasma beta-endorphin levels and left ventricular systolic
      performance as assessed by M-mode and Doppler echocardiography. Plasma beta
      endorphin levels were negatively correlated with cardiac output determined by
      Doppler echocardiography and positively correlated with systemic vascular
      resistance (r = -0.733, r = 0.747, respectively, both p less than 0.001), but not
      correlated with calf blood flow as measured by a plethysmography. A good
      correlation was found between plasma beta-endorphin levels at rest and exercise
      capacity. The correlations with peak oxygen consumption, anaerobic threshold, and
      peak rate-pressure product were r = -0.721, -0.672, and -0.674, respectively (p
      less than 0.01). The data show that plasma beta-endorphin levels are elevated in
      patients with congestive heart failure and reflect, to some degree, the severity
      of the disease.

PMID- 1987242
TI  - Superiority of transesophageal echocardiography in detecting cardiac source of
      embolism in patients with cerebral ischemia of uncertain etiology.
AB  - The diagnostic yield of transesophageal and transthoracic echocardiography for
      identifying a cardiac source of embolism was compared in 79 patients presenting
      with unexplained stroke or transient ischemic attack. There were 35 men and 44
      women with a mean age of 59 years (range 17 to 84); 52% had clinical cardiac
      disease. Both transthoracic and transesophageal echocardiograms were performed
      using Doppler color flow and contrast imaging. Transesophageal echocardiography
      identified a potential cardiac source of embolism in 57% of the overall study
      group compared with only 15% by transthoracic echocardiography (p less than
      0.0005). Compared with transthoracic echocardiography, transesophageal
      echocardiography more frequently identified atrial septal aneurysm associated
      with a patent foramen ovale (9 versus 1 of 79 patients, p less than 0.005), left
      atrial thrombus or tumor (6 versus 0 of 79 patients, p less than 0.05) and left
      atrial spontaneous contrast (13 versus 0 of 79 patients, p less than 0.0005). All
      cases of left atrial thrombus or spontaneous contrast were identified in patients
      with clinically identified cardiac disease. In the 38 patients with no cardiac
      disease, transesophageal echocardiography identified isolated atrial septal
      aneurysm and atrial septal aneurysm with a patent foramen ovale more frequently
      than transthoracic echocardiography (8 versus 2 of 38 patients, p less than
      0.05). The two techniques had a similar rate of identifying apical thrombus and
      mitral valve prolapse. Overall, transesophageal echocardiography identified
      abnormalities in 39% of patients with no cardiac disease versus 19% for
      transthoracic echocardiography (p less than 0.005). Thus, transesophageal
      echocardiography identifies potential cardiac sources of embolism in the majority
      of patients presenting with unexplained stroke.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1987241
TI  - Implications of echocardiographically assisted diagnosis of pericardial tamponade
      in contemporary medical patients: detection before hemodynamic embarrassment.
AB  - Identification of suspected pericardial tamponade and the decision to perform
      invasive drainage of the pericardial space have historically been based on
      classic bedside findings. Two-dimensional echocardiography has improved detection
      of pericardial effusion, but it may be excessively sensitive in evaluation of
      patients for hemodynamic embarrassment. Therefore, 50 consecutive medical
      patients were examined who were identified by echocardiography to have probable
      tamponade (defined as the presence of right heart chamber collapse in the
      presence of a pericardial effusion) and who underwent combined right-sided
      cardiac catheterization and percutaneous pericardiocentesis. All patients had
      elevated pericardial pressure. However, many had minimal evidence of hemodynamic
      compromise (94% had systolic blood pressure greater than or equal to 100 mm Hg
      and 58% had a cardiac index greater than or equal to 2.3 liters/min per m2).
      Pericardiocentesis resulted in hemodynamic improvement, but frequently did not
      alleviate dyspnea or correct tachycardia. Patients with malignancy as the cause
      of tamponade had a high mortality rate (the cumulative probability of survival in
      such patients was only 17% at 1 year). Echocardiographically assisted diagnosis
      of pericardial tamponade in medical patients results in the identification of a
      substantial subset of patients with only subtle evidence of hemodynamic
      compromise. This subset of patients differs sharply from medical patients
      described in previous reports with classic tamponade. Although the patients can
      be managed by invasive catheter pericardiocentesis with few complications, the
      natural history and the optimal management strategy for this group are not
      resolved.

PMID- 1987243
TI  - Recognition and embolic potential of intraaortic atherosclerotic debris.
AB  - Atherosclerotic disease of the thoracic aorta is common in the elderly and
      patients with clinical coronary artery disease. Although embolization can occur
      from atherosclerotic debris within the thoracic aorta, it is not commonly
      considered in the differential diagnosis of the source of a systemic embolism. In
      the current study, the prevalence, clinical significance and embolic potential of
      intraaortic atherosclerotic debris as detected by transesophageal
      echocardiography was determined. Intraaortic atherosclerotic debris was
      identified in 38 (7%) of 556 patients undergoing transesophageal
      echocardiography. An embolic event occurred among 11 (31%) of the 36 study
      patients with intraaortic atherosclerotic debris. The incidence of an embolic
      event was higher when the debris was pedunculated and highly mobile (8 [73%] of
      11 patients) than when it was layered and immobile (3 [12%] of 25 patients) (p
      less than 0.002). Among 15 patients undergoing an invasive procedure of the
      aorta, the incidence of embolism was 27%. In conclusion, in a patient with an
      embolic event, the thoracic aorta should be considered as a potential source.
      Transesophageal echocardiography can reliably detect intraaortic atherosclerotic
      debris, and when it is identified, an invasive aortic procedure should be avoided
      if possible.

PMID- 1987244
TI  - Coronary arterial remodeling studied by high-frequency epicardial
      echocardiography: an early compensatory mechanism in patients with obstructive
      coronary atherosclerosis.
AB  - Coronary arterial remodeling is a compensatory mechanism that may limit the
      adverse effects of coronary obstructive lesions by expansion of the entire
      vascular segment. To determine if this compensatory anatomic change occurs in
      patients, high-frequency epicardial echocardiography using a 12 MHz transducer
      was performed during open heart surgery in 33 patients (10 with normal coronary
      arteries undergoing valvular surgery and 23 with coronary atherosclerosis). From
      stop-frame videotape high-frequency epicardial echocardiographic images, cross
      sectional measurements of luminal area and total arterial area (lumen, intima,
      media and dense adventitia) were made in the patients with atherosclerosis at the
      site of arterial lesions and from the most proximal portion of the same artery.
      Remodeling was defined as enlargement of the total arterial area. In normal
      arteries measurements were made from proximal and midarterial locations. In the
      patients with normal coronary arteries, total arterial area, as determined by
      high-frequency echocardiography, decreased from the proximal site to the
      midportion of the artery (from 10.4 +/- 0.9 to 8.4 +/- 1.0 mm2, p less than
      0.05); luminal area also decreased (from 6.0 +/- 0.6 to 4.5 +/- 0.7 mm2, p less
      than 0.05). In patients with coronary arterial lesions, luminal area also
      decreased from the proximal site to the arterial lesion site (from 5.3 +/- 0.6 to
      2.3 +/- 0.3 mm2, p less than 0.05), but total arterial area increased (from 11.6
      +/- 1.0 to 13.0 +/- 1.0 mm2, p less than 0.05). Of the 25 coronary arteries
      evaluated, only 4 had angiographic evidence of coronary collateral formation.
      These data indicate that coronary arterial remodeling is an important
      compensatory mechanism in obstructive coronary disease.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1987245
TI  - Detection of coronary blood flow associated with left main coronary artery
      stenosis by transesophageal Doppler color flow echocardiography.
AB  - Demonstration of disordered blood flow in a coronary artery may be helpful in
      anticipating the presence of stenosis. To examine the possibility of disordered
      coronary blood flow associated with left main coronary stenosis, left main
      coronary flow was visualized by transesophageal Doppler color flow
      echocardiography in 52 patients undergoing coronary angiography. Twenty patients
      had significant left main coronary stenosis (Group 1) and 32 patients did not
      (Group 2). Adequate two-dimensional echocardiographic images of the left main
      coronary artery were obtained in 17 patients in Group 1 and 30 patients in Group
      2. Sixteen patients in Group 1, including five patients in whom the stenosis
      could not clearly be defined by two-dimensional echocardiography, exhibited the
      aliased reddish-yellowish elements producing the mosaic pattern at the stenotic
      or poststenotic segments, or both. In contrast, nonaliased bluish jets,
      suggesting laminar flow away from the transducer, were seen in echocardiograms
      from 27 patients in Group 2. This group included four patients with stenosis-like
      images on two-dimensional echocardiography. The aliased mosaic pattern was found
      in only three patients in Group 2 (p less than 0.01). Thus, sensitivity to detect
      the stenosis was improved when Doppler color flow imaging was applied. Flow
      velocity was significantly higher at the site of stenosis in patients in Group 1
      (116 +/- 28 cm/s, n = 10, mean +/- SD) than in Group 2 (29 +/- 12 cm/s, n = 21, p
      less than 0.01), suggesting that the augmentation of flow velocity with or
      without turbulence due to the stenosis contributed to the appearance of the
      mosaic flow images.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1987246
TI  - Percutaneous coronary excimer laser-assisted balloon angioplasty: initial
      clinical and quantitative angiographic results in 50 patients.
AB  - The initial clinical experience and quantitative angiographic results of
      percutaneous coronary excimer laser-assisted balloon angioplasty are described
      for 55 lesions in 50 patients. With use of a xenon chloride (308 nm) excimer
      laser generator and 1.5 to 1.75 mm catheters, excimer laser angioplasty was
      attempted at 135 ns pulse width, 25 to 40 Hz repetition rate, 2 to 5 s laser
      delivery time and 30 to 60 mJ/mm2 energy fluence. Laser success (greater than 20%
      reduction in absolute percent diameter stenosis) was achieved in 41 (75%) of 55
      lesions, with 100% subsequent balloon angioplasty success (less than 50% residual
      stenosis). By quantitative digital caliper technique, the percent diameter
      stenosis (mean +/- SE) was reduced from 81 +/- 1% to 50 +/- 3% after excimer
      laser angioplasty (p less than 0.001) and to 20 +/- 1% after balloon angioplasty
      (p less than 0.001); minimal luminal diameter increased from 0.56 +/- 0.04 to
      1.46 +/- 0.08 mm (p less than 0.001) and 2.03 +/- 0.07 mm (p less than 0.001),
      respectively. By videodensitometric techniques, the percent area stenosis
      decreased from 86 +/- 2% to 54 +/- 3% after excimer angioplasty (p less than
      0.001) and to 26 +/- 3% after balloon angioplasty (p less than 0.001). There were
      no perforations, need for emergency bypass surgery or deaths. The overall
      incidence of abrupt closure (3.6%), dissection (1.8%), embolization (1.8%),
      filling defect (6%), myocardial infarction (5.5%), side branch occlusion (3.6%)
      or spasm (3.6%) was infrequent and more related to subsequent balloon angioplasty
      than to the laser procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1987247
TI  - Is routine preoperative hemodynamic evaluation of nonagenarians necessary?
AB  - An Incidence of co-morbid cardiac disease in the elderly surgical patient as high
      as 66% has been previously reported. Even in the absence of clinically
      significant cardiac disease, advanced age alone is often considered sufficient
      indication for Swan-Ganz placement, hemodynamic evaluation, adjustment of fluid
      states, and inotropic support. Yet data clearly documenting the need for this
      evaluation and therapy are difficult to obtain. All major general surgical and
      orthopedic operations in non-agenarians were reviewed in our institution from
      July 1, 1987 through December 31, 1988. Fifty-one procedures were performed on 46
      patients. None of these patients had preoperative Swan-Ganz catheterization or
      hemodynamic evaluation. Eighteen general surgical, 30 orthopedic, 2
      neurosurgical, and 1 gynecological procedures were performed. Forty-three were
      performed under general anesthesia, 7 under spinal anesthesia, and 1 with local
      anesthesia. Seven out of 51 patients (14%) experienced major complications, and
      16 out of 51 (31%) experienced minor complications. Thirty-day mortality was 0%,
      and 6-month survival was 92%. Only one complication occurred within 48 hours of
      surgery that might possibly have been prevented with hemodynamic evaluation,
      adjustment of fluid status, inotropic support, and intensive care unit
      monitoring.

PMID- 1987249
TI  - Reducing polypharmacy.

PMID- 1987248
TI  - Prognosis of acute renal failure among elderly patients.

PMID- 1987250
TI  - Do not resuscitate policies.

PMID- 1987251
TI  - Macromastia in an elderly woman.

PMID- 1987252
TI  - Patients in a persistent vegetative state attitudes and reactions of family
      members.
AB  - Patients in a persistent vegetative state (PVS) constituted approximately 3% of
      the population in four Milwaukee nursing homes. In order to understand family
      members' attitudes and reactions toward such patients, 33 (92%) of 36 family
      members of patients in PVS contacted were studied. The age of the patients ranged
      from 19 to 95 with a mean age of 73.4 +/- 17.2 years, and family members' ages
      ranged from 41 to 89 with a mean age of 61.8 +/- 3.3 years. The etiology of the
      PVS varied from dementia to cerebral trauma. The mean duration of the PVS was 54
      +/- 8.4 months (range 12 to 204). Family members reported that they visited
      patients 260 times during the first year following the onset of the PVS and were
      still visiting at a rate of 209 visits yearly at the time of the interview. There
      was no significant correlation between the frequency of the family members visits
      and the duration of the PVS, the patient's or family member's age, or the family
      member's relationship to the patient. Ninety percent of patients were considered
      by family members to have some awareness of pain, light or darkness, environment,
      taste, verbal conversation, or the family member's presence. Most family members
      thought they understood the patient's medical condition, and the majority did not
      expect the patient to improve. Nevertheless, the majority of family members
      wanted the patient to undergo therapeutic interventions, including transfer to
      the acute hospital and surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1987253
TI  - Breast cancer screening in older women: practices and barriers reported by
      primary care physicians.
AB  - Annual mammography, in combination with clinical breast examinations, can reduce
      mortality from breast cancer. However, surveys of both patients and physicians
      suggest that mammography is underutilized. This study examined whether
      physicians' reported breast cancer screening practices and barriers to
      mammography varied with patients' age. Data from 576 primary care physicians
      (internal medicine, family/general practice, and obstetrics/gynecology) who
      participated in a mailed statewide survey were analyzed. Physicians reported
      screening elderly women significantly less often than younger women, regardless
      of family history of breast cancer. With the exception of medical specialty,
      physicians' demographic and practice characteristics were not associated with
      reported screening practices. However, physicians' knowledge and beliefs about
      breast cancer in older women were associated with reported screening practices.
      When analyzing barriers to ordering mammography, cost to the patient was viewed
      as a barrier for women of all ages, and pain was viewed as a greater barrier for
      younger women; otherwise, physicians consistently believed that their elderly
      patients faced considerably more barriers compared with younger women. Further
      investigation is required to examine why primary care physicians report age
      related differences in both breast screening and barriers to mammography.

PMID- 1987254
TI  - Erythropoietin response to anemia as a function of age.
AB  - The erythropoietin (EPO) response to anemia was assessed for 244 subjects aged 1
      64 years (mean 45.2 years) and 121 subjects aged 65-94 years (mean 68.3 years).
      Subjects included non-anemic individuals as well as those with anemia of various
      etiologies, excluding renal disease and pregnancy. Significant inverse
      correlations between serum immunoreactive EPO and hematocrit were noted for both
      groups. Regression lines failed to show a significantly lower slope or y
      intercept for older compared to younger subjects. EPO levels were not
      significantly lower for older compared to younger subjects when controlled for
      hematocrit level. These results suggest that the EPO response to anemia in older
      subjects is similar to that of younger subjects.

PMID- 1987255
TI  - Progression of cognitive impairment in Alzheimer's disease.
AB  - Change in cognitive function was assessed over 12 months in 110 patients over the
      age of 65 satisfying National Institute of Neurological and Communicative
      Disorders and Stroke and the Alzheimer's Disease and Related Disorders
      Association (NINCDS/ADRDA) criteria for "probable" Alzheimer's Disease. A highly
      significant deterioration in cognitive function was observed. Decline in
      cognitive scores was relatively normally distributed. Patients who died during
      the follow-up had more apraxia at entry to the study than survivors. A greater
      rate of decline was seen in patients whose parents suffered from dementia (but
      not in those where a sibling or other relative was affected), in subjects who had
      moderate dementia, and those who had been ill for less than 24 months. Age, age
      of onset, and the presence or absence of aphasia or apraxia had no influence on
      rate of progression. A cluster analysis revealed three patterns of decline.

PMID- 1987256
TI  - Falls and injuries in frail and vigorous community elderly persons.
AB  - Identification of different types of falls and fallers among elderly persons
      might aid in the targeting of preventive efforts. In a representative sample of
      336 community elderly, subjects were assigned to Frail, Vigorous, or Transition
      groups based on observed patterns of clustering among demographic, physical, and
      psychological variables. The frequency and circumstances of falls in these three
      groups were then ascertained. As expected, the observed incidence of falling in
      one year of follow-up was highest in the Frail group (52%) and lowest in the
      Vigorous group (17%). However, 22% (5/23) of falls by vigorous subjects, but only
      6% (5/89) of falls by frail subjects, resulted in a serious injury. Compared with
      frail subjects, vigorous fallers were somewhat more likely to fall during
      displacing activity (53% vs 31%), with an environmental hazard present (53% vs
      29%), and on stairs (27% vs 6%). These findings suggest that fall-related
      injuries can be a serious health problem for vigorous as well as frail elderly
      persons. Injury prevention, therefore, should be directed at all elderly persons
      but tailored to expected differences in fall circumstances.

PMID- 1987257
TI  - Forearm blood flow response to posture change in the very old: non-invasive
      measurement by venous occlusion plethysmography.
AB  - Little is known about the peripheral vascular response to posture change in very
      elderly people who are vulnerable to the development of orthostatic hypotension.
      This is due, in part, to the risks of currently utilized invasive vascular
      monitoring techniques in the elderly population. We studied the forearm vascular
      response to active standing in 18 healthy young, 10 healthy old, and 19 impaired
      elderly subjects, using the non-invasive technique of venous occlusion
      plethysmography. In six subjects this technique was compared to duplex doppler
      ultrasonography for the measurement of postural changes in forearm blood flow.
      Forearm blood flow changes determined by venous occlusion plethysmography were
      11% larger than doppler measurements, but the two methods strongly correlated (r
      = 0.90, P less than .001). Mean forearm vascular resistance increased to a
      significantly greater extent at 1 minute of standing in young subjects than in
      both groups of old, although the response was quite variable in all groups. Two
      healthy elderly (20%) and eight impaired elderly (40%) subjects had unexpected
      forearm vasodilatation at 1 minute of standing. By 3 minutes, forearm vascular
      resistance had increased by similar amounts in all three groups of subjects. Five
      impaired elderly and no healthy young or healthy old subjects had orthostatic
      hypotension, defined as greater than or equal to 10 mm Hg decline in mean
      arterial blood pressure at 1 or 3 minutes of standing. Forearm vascular
      resistance changes did not correlate with blood pressure response to standing.
      Thus, forearm vascular response to 1 minute of active standing is attenuated in
      many elderly subjects. This abnormality may impair adaptation to orthostatic
      stress in advanced age.

PMID- 1987258
TI  - Ostium secundum atrial septal defect in the elderly.
AB  - Atrial septal defect (ASD) is one of the most common congenital cardiac anomalies
      in adults. Life expectancy is shortened, and almost 90% of patients die by the
      age of 60 years. The progression of this congenital disease to congestive heart
      failure has been related to several factors such as the onset of pulmonary
      hypertension, arrhythmias, bronchopulmonary infections, or the development of
      other cardiovascular disease. We describe three cases of very old patients with
      significant ASDs and late development of symptoms. Given the higher risks and
      poorer long-term results of surgical closure of the defect in advanced age, the
      indications for such an intervention in elderly patients should be carefully
      evaluated.

PMID- 1987259
TI  - Weakening the bonds of friendship: an unfortunate outcome of the Cruzan
      decisions.

PMID- 1987261
TI  - Dose response of hepatic and renal DNA synthetic rates to continuous exposure of
      bromodeoxyuridine (BrdU) via slow-release pellets or osmotic minipumps in male
      B6C3F1 mice.
AB  - We studied the use of acute and chronic 5-bromo-2'-deoxyuridine (BrdU)
      administration for detection of DNA-synthesizing cells in the liver and kidney of
      B6C3F1 male mice. Six-week-old mice were exposed to BrdU either acutely with a
      single-pulse (IP) injection 1 hr before sacrifice or chronically with the use of
      slow-release pellets or osmotic minipumps at one of four BrdU dose rates. Pellets
      (2.5, 10, 25, and 50 mg) and minipumps (2.5 and 10 mg equivalents) were implanted
      subcutaneously on the backs of the animals 4 or 7 days before sacrifice). BrdU
      incorporation into DNA was determined by immunohistochemistry using an anti-BrdU
      antibody. Mice chronically exposed to BrdU demonstrated increased levels of
      nuclear labeling compared with those receiving a single-pulse injection. No time
      related increases in nuclear labeling were detected in hepatocytes or renal
      tubule cells of mice exposed to BrdU pellets and in the kidneys of mice receiving
      BrdU minipumps at the 7-day compared with the 4-day time point. In some cases,
      the labeling indices at 7 days were significantly decreased compared with those
      at 4 days. In contrast, a time-related increase in nuclear labeling was seen in
      hepatocytes and Kupffer cells of mice exposed to BrdU minipumps. Therefore, the
      method used to administer BrdU chronically to the animal appears to play an
      important role in presenting the true proliferative scenario in cell kinetic
      studies. Our findings also provide evidence for an effect of BrdU on normal
      proliferation rates in these tissues.

PMID- 1987260
TI  - Detection of interphotoreceptor retinoid binding protein (IRBP) mRNA in human and
      cone-dominant squirrel retinas by in situ hybridization.
AB  - Interphotoreceptor retinoid binding protein (IRBP) is a soluble glycolipoprotein
      located between the neurosensory retina and pigment epithelium, which may serve
      to transport vitamin A derivatives between these tissues. The specific cell type
      responsible for IRBP synthesis has not been well established. To address this
      issue, we have examined the expression of IRBP mRNA in human and cone-dominant
      ground squirrel retinas by in situ hybridization. Optimal labeling and
      histological resolution were achieved with 35S- and 3H-labeled anti-sense
      riboprobes made from a human IRBP cDNA clone, and semi-thin wax-embedded retinal
      sections. In human retina, label was localized over the inner segments of both
      rod and cone photoreceptors. Quantitative analysis demonstrated a fourfold higher
      density of label over rod inner segments. In ground squirrel retina, labeling was
      found almost exclusively over the inner segments of cones. The results indicate
      that in human retina both rods and cones express IRBP mRNA, albeit at different
      levels. In cone-dominant species such as the ground squirrel, cones are the
      principal cell type responsible for IRBP mRNA synthesis.

PMID- 1987262
TI  - Ultrastructural localization of HTLV-I gag proteins p19 and p24 by single and
      double immunogold labeling.
AB  - We developed a post-embedding immunogold labeling procedure for the
      ultrastructural localization of the HTLV-I gag proteins p19 and p24 by the use of
      monoclonal antibodies (MAb). Both antigens were shown to withstand fixation with
      1% glutaraldehyde. In addition, p19 antigenicity was found not to be affected by
      post-fixation with 1% osmium tetroxide. The choice of resin played a decisive
      role in the retention of antigenicity. P19 was preserved in Lowicryl K4M as well
      as in LR White, whereas p24 was preserved only in Lowicryl. Both p19 and p24 were
      found to be localized on the HTLV-I virions themselves, whereas no positive
      immunostaining could be observed on the infected cells. In Lowicryl-embedded
      samples, in which both antigens had been preserved, a double immunogold labeling
      procedure was performed that allowed the co-localization of p19 and p24 on the
      same section. In osmicated LR White-embedded samples the quality of
      ultrastructural preservation of HTLV-I virions was found to be comparable to
      results obtained with the traditional glutaraldehyde-osmium tetroxide-epoxy resin
      processing.

PMID- 1987264
TI  - Activity of alkaline phosphatase in rat skeletal muscle localized along the
      sarcolemma and endothelial cell membranes.
AB  - Alkaline phosphatase (AP), a membrane-associated glycoprotein which enhances the
      hydrolysis of monophosphate esters at alkaline pH, is widely distributed in
      animal tissues. AP activity is increased in a variety of muscle disorders, i.e.,
      myopathies and denervation. Established histochemical methods at the light
      microscopy level failed to demonstrate AP in skeletal muscles. In the present
      study we applied the Gomori lead nitrate method for ultrastructural examination
      of AP in rat gastrocnemius muscles and showed that the enzyme was linked to the
      sarcolemma of the striated muscle and to the membranes of endothelial cells in
      adjacent capillaries. In comparison with ATPase activity, AP activity was
      inhibited by both levamisole and a pH of 7.2, but not by ouabain. Hence, it
      appears that in skeletal muscles AP is active at a high pH and is bound to cell
      membranes.

PMID- 1987263
TI  - Identification of phospholipids in secretory granules of human submucosal gland
      respiratory cells.
AB  - Although it has been shown that tracheal epithelial cells in culture synthesize
      and secrete phospholipids, no direct evidence for in situ phospholipid storage in
      human respiratory secretory epithelial cells has been demonstrated. We used a
      high-resolution cytochemical enzyme-gold technique to identify and precisely
      localize phospholipids in human submucosal gland secretory cells. In addition,
      lysozyme, a specific serous cell marker, was identified using the
      biotinstreptavidin gold technique with lysozyme antiserum. This double labeling
      of phospholipids and lysozyme was performed using gold particles of diameters 15
      nm and 5 nm, respectively. Quantitation of phospholipid labeling was performed on
      an image analyzer. Phospholipids were identified in serous granules (8.87 +/-
      2.21 gold particles/microns 2) in a significantly (p less than 0.05) higher
      density than in mucous granules (5.57 +/- 3.07 gold particles/microns 2). These
      results support the hypothesis that submucosal human airway serous and mucous
      secretory cells produce phospholipids which may be secreted in the airway lumen.

PMID- 1987265
TI  - Chromogranins or chromogranin-like proteins are present in lamellar bodies and
      pulmonary surfactant of rat alveolar type II cells.
AB  - Rat alveolar Type II cells were immunostained with antibodies directed against
      chromogranin A (monoclonal, LK2H10) and chromogranins A and B (polyclonal,
      LKZM1U). The chromogranins or chromogranin-like proteins were identified in cells
      in lung tissue sections and isolated Type II cells at the light and electron
      microscopic levels. We used post-embedding immunoelectron microscopy, with
      immunogold, to detect the proteins' immunoreactivity in osmicated tissues. Gold
      particles were distributed over the phospholipid lamellae within the lamellar
      bodies of alveolar Type II cells and over the lattice structure of tubular
      myelin. Quantitative analysis of gold labeling densities in the various cell
      compartments indicated that only the latter two structures were specifically
      labeled. Controls, which included pre-absorption of both anti-chromogranin
      antibodies with excess chromogranin A or with native surfactant, resulted in a
      greater than 60% decrease in gold labeling. A possible role of chromogranins or
      chromogranin-like proteins as Ca2+ binding proteins in alveolar Type II cells is
      discussed.

PMID- 1987266
TI  - Effects of formaldehyde fixation on protein secondary structure: a calorimetric
      and infrared spectroscopic investigation.
AB  - We investigated the effects of formaldehyde fixation on the secondary structure
      of isolated proteins (bovine serum albumin, ribonuclease A, and hemoglobin) using
      high-sensitivity differential scanning calorimetry and Fourier transform infrared
      spectroscopy. Whereas thermograms obtained by scanning calorimetry on unfixed
      purified proteins demonstrated denaturation transitions in the 70-90 degrees C
      temperature range, the thermograms showed no denaturation transitions in this
      temperature range when the proteins had been placed in formaldehyde solutions.
      Thus, fixation destroyed the denaturation transition of bovine serum albumin,
      ribonuclease A, and hemoglobin. Infrared spectra obtained on the unfixed and
      fixed proteins were essentially identical. This demonstrates that the "fixed"
      proteins retain the secondary structure present before fixation. We therefore
      conclude that the cross-linking of proteins that occurs in the process of
      formaldehyde fixation "locks in" the secondary structure of these protein
      molecules.

PMID- 1987267
TI  - Increased sensitivity of the indirect immunofluorescence method by use of a
      tertiary fluorochrome-labeled antibody.
AB  - The standard protocol for indirect immunofluorescence was modified by the
      addition of a third layer of antibodies. These antibodies were conjugated with
      the same fluorochrome as the secondary antibodies. This modification resulted in
      significant enhancement of the sensitivity of immunolabeling. The method may be
      useful when the standard indirect immunofluorescent technique results in weak
      labeling, and also to regain labeling in sections where specific fluorescence has
      faded.

PMID- 1987268
TI  - Characterization of AL amyloid protein identified by immunoelectron microscopy: a
      simple method using the protein A-gold technique.
AB  - The classification of amyloidosis depends on the chemical nature of the specific
      amyloid protein involved. Because AL amyloid protein consists mainly of variable
      regions of light chain (LC), immunohistochemical staining with conventional anti
      LC antisera cannot identify its protein. We were able to classify three cases of
      AL amyloidosis, including one case of AL-kappa LC and two cases of AL-lambda LC,
      using post-embedding protein A-gold immunoelectron microscopy on autopsy-derived
      tissues. We describe here our procedure in which a protein A-gold staining
      apparatus was used. The main advantage of this method is that many sections can
      be stained and washed simultaneously under the same conditions. These results
      suggest that the post-embedding protein A-gold technique using conventional kappa
      or lambda LC may be useful in diagnosing AL amyloidosis.

PMID- 1987269
TI  - Quantification of chemotactic response of quiescent and proliferating fibroblasts
      in Boyden chambers by computer-assisted image analysis.
AB  - The chemotactic response of human gingival fibroblasts to platelet-derived growth
      factor (PDGF) was investigated in 48-well modified Boyden chambers. Results were
      quantified using computer-assisted image analysis of propidium iodidestained
      cells and were compared with results obtained using the conventional method of
      quantification by direct counting. Quantification by image analysis was found to
      be rapid and accurate, and correlated closely with results obtained by direct
      counting. Bromodeoxyuridine (BrdU)-labeled proliferating cells were double
      stained with propidium iodide and fluorescein isothiocyanate (FITC)-conjugated
      anti-BrdU antiserum. The cycling cells showed a markedly reduced chemotactic
      response to PDGF, whereas cells in S-phase of the cell cycle did not show any
      response. This method of quantification of results of Boyden chamber assays is
      simple and reliable, and allows the use of double labels to investigate the
      chemotactic response of subpopulations of cells within a heterogeneous population
      of cells.

PMID- 1987270
TI  - Mutations affecting antigen processing impair class II-restricted
      allorecognition.
AB  - Both exogenously derived and endogenously derived Ag generally require processing
      for their optimal binding and presentation by class I and class II major
      histocompatibility proteins. It is not known whether steps involved in Ag
      processing also affect the recognition of alloreactive T cells. We have recently
      described B cell mutants which have general defects in the processing and
      presentation of a variety of exogenous Ag to class II restricted T cells. In this
      report we have studied the ability of these processing mutants to stimulate a set
      of anti-DR3-specific alloreactive T cells clones. These processing/presentation
      mutants express normal MHC class II molecules, both in terms of primary sequence
      and cell surface abundance, but they appear unable to generate effective peptide
      MHC complexes. When tested for their ability to stimulate MHC class II
      alloreactive T cell clones, only one of four T cell clones was stimulated by
      these mutants; the other three alloreactive T cell clones were not stimulated by
      either of two different mutants. Both of these mutants express normal levels of
      the accessory molecules, LFA-3 and ICAM-1. The inability of these mutants to
      stimulate three of four alloreactive clones indicates that the capacity to be
      recognized by many alloreactive T cells is linked to the Ag processing capacity
      of a stimulator cell.

PMID- 1987271
TI  - Separation and characterization of saponins with adjuvant activity from Quillaja
      saponaria Molina cortex.
AB  - Saponins were purified from Quillaja saponaria Molina bark by silica and reverse
      phase chromatography. The resulting purified saponins were tested for adjuvant
      activity in mice. Several distinct saponins, designated QS-7, QS-17, QS-18, and
      QS-21, were demonstrated to boost antibody levels by 100-fold or more when used
      in mouse immunizations with the Ag BSA and beef liver cytochrome b5. These
      purified saponins increased titers in all major IgG subclasses. To determine
      optimal dose in mice for adjuvant response, QS-7 and QS-21 were tested in a dose
      response study in intradermal immunization with BSA in mice; for both of these
      purified saponins, adjuvant response (determined by stimulation of ELISA titers
      to BSA) neared maximum at doses of 5 micrograms and was shown to plateau up to
      the highest dose tested, 80 micrograms. These purified saponins vary considerably
      in their toxicity, as assessed by lethality in mice; the main component, QS-18,
      being the most toxic. Saponins QS-7 and QS-21 showed no or very low toxicity in
      mice, respectively. None of these saponins stimulated production of reaginic
      antibodies. The monosaccharide composition of these saponins showed similar but
      distinct compositions with all four containing fucose, xylose, galactose and
      glucuronic acid. Predominant differences were observed in the quantities of
      rhamnose, arabinose, and glucose. Monomer m.w. (determined by size exclusion
      HPLC) were determined to range from 1800 to 2200.

PMID- 1987272
TI  - Weak base amines can inhibit class I MHC-restricted antigen presentation.
AB  - This report describes the effects of NH4Cl, CH3NH2, and chloroquine on class I
      and II MHC-restricted Ag presentation. OVA-specific T-T hybridomas were used to
      detect processed OVA in association with class I, H-2Kb, and class II, I-Ad/b,
      molecules on a B lymphoblastoid APC. OVA, internalized by APC under hypertonic
      conditions, was presented in association with class I and II MHC molecules.
      Treating the APC with NH4Cl or CH3NH2 inhibited class I- and II-restricted Ag
      presentation. In contrast, chloroquine markedly inhibited class II, but not class
      I-restricted Ag presentation. Controls indicated that drug-treated APC were fully
      competent to interact with T cells and present processing-independent antigenic
      peptides in association with both class I and II MHC molecules. NH4Cl and CH3NH2
      did not inhibit the uptake of radiolabeled Ag by the APC. After the proteolytic
      removal of H-2Kb from the surface of APC, NH4Cl and CH3NH2-treated and control
      APC regenerated identical amounts of surface H-2Kb and this regeneration required
      de novo protein synthesis. These latter results indicate that NH4Cl and CH3NH2
      can inhibit Ag presentation without affecting the synthesis, transport, or
      surface expression of H-2Kb. Also, NH4Cl did not affect the transport of H-2Db to
      the surface of mutant RMA-S cells that were cultured with exogenous peptides.
      Taken together these results strongly suggest that NH4Cl and CH3NH2 but not
      chloroquine can inhibit a critical and early intracellular step in class I
      restricted Ag presentation while simultaneously inhibiting class II-restricted Ag
      presentation.

PMID- 1987273
TI  - Staphylococcal exotoxin activation of T cells. Role of exotoxin-MHC class II
      binding affinity and class II isotype.
AB  - Staphylococcal enterotoxins (SE) and toxic shock syndrome toxin-1 bind directly
      to class II molecules of the MHC and stimulate T cells based predominantly on the
      V beta segment used by the TCR. We investigated the relationship between the
      class II binding affinities of four of these exotoxins, SEA, SEB, SEC1, and toxic
      shock syndrome toxin-1 and their T cell signaling capabilities. Although the
      toxins stimulated T cells at concentrations that ranged over more than two orders
      of magnitude, their affinities for class II (DR1) differed by less than sixfold.
      The affinities of the toxins predicted their capacity to stimulate resting T
      cells to proliferate. The binding affinities of the toxins for class II molecules
      indicated that at concentrations required for T cell stimulation, as few as 0.1%
      of the class II molecules are complexed with toxin. Finally, the isotype of class
      II molecules affected the ability of the toxins to bind and use these MHC Ag to
      stimulate T cells. These data thus demonstrate that of the staphylococcal
      exotoxins studied, both their potency as T cell mitogens and their ability to
      function in the presence of single class II isotypes can be attributed in part to
      their characteristic abilities to bind class II molecules.

PMID- 1987274
TI  - Delayed-type hypersensitivity initiation by early-acting cells that are antigen
      mismatched or MHC incompatible with late-acting, delayed-type hypersensitivity
      effector T cells.
AB  - The elicitation of delayed-type hypersensitivity (DTH) responses in mice is
      mediated by the sequential activities of two different Ag-specific, Thy-1+ cells.
      A required early phase of elicitation is due to DTH-initiating Thy-1+ cells that
      are CD3- and sIg- and produce Ag-specific factors that act like IgE antibodies in
      that they sensitize the tissues, so that after local challenge with Ag there is
      release of the vasoactive amine serotonin. Released serotonin locally recruits
      and activates CD4+ Th-1 classical DTH effector T cells that secrete lymphokines
      that attract and activate a nonspecific perivascular infiltrate of circulating,
      bone marrow-derived leukocytes. The current study used isolated subpopulations of
      DTH-initiating and DTH-effector T cells to determine whether the two phases of
      the elicitation of DTH were entirely separate. The contact sensitivity model of
      DTH was used. Early-acting DTH-initiating cells, and late-acting DTH-effector T
      cells were either from oxazolone (OX)-immune or picryl chloride (PCl)-immune CBA
      or BALB/c donors and were transferred to CBA or BALB/c recipients. The results
      showed that DTH-initiation could be mediated by polyclonal DTH-initiating cells
      that were Ag mismatched or MHC incompatible with late-acting DTH effector T
      cells. In fact DTH-initiating cells could be both Ag mismatched and MHC
      incompatible with late-acting T cells. In addition, potential interactions
      between different cell populations were ruled out by showing that DTH-initiation
      could be mediated by a DTH-initiating clone that was Ag or MHC mismatched with
      the late-acting DTH-effector T cells. Thus, the OX-specific BALB/c clone could
      initiate DTH for PCl-specific CBA cells in CBA recipients if the recipients were
      challenged with both OX and PCl, but not when they were challenged with OX or PCl
      alone. We suggest, at least for the elicitation of DTH reactions in mice, that a
      more comprehensive description of these responses should accommodate the fact
      that there are early and late phase responses that each begin with Ag specificity
      and end with non-specific humoral factors. Inasmuch as the two Thy-1+ cells of
      DTH can be of different Ag specificity, this suggests that some forms of delayed
      and chronic inflammation, might be initiated by an immediate hypersensitivity
      like immune reactivity to one set of Ag, and could be prolonged and perpetuated
      by delayed reactivity to another set of Ag.

PMID- 1987275
TI  - Cellular and subcellular distribution of PBP72/74, a peptide-binding protein that
      plays a role in antigen processing.
AB  - A 72/74-kDa peptide binding protein (PBP72/74) was previously described which
      plays a role in the processing and/or presentation of Ag, possibly by
      facilitating the association of processed Ag with the MHC class II molecules.
      PBP72/74 was recently shown to be related to the 70-kDa family of heat shock
      proteins (hsp70), whose members show the general characteristic of binding to
      denatured or inappropriately folded proteins. Here we describe the cellular and
      subcellular distribution of PBP72/74. By flow cytometry with PBP72/74-specific
      rabbit antisera, PBP72/74 is detected on the surfaces of mouse Ig+ B cells and
      MAC-1+ macrophages. PBP72/74 74 was not detected on the surfaces of Thy-1+ T
      cells or NK1.1+ NK cells. The cell surface expression of PBP72/74 does not
      require MHC class II expression. Indeed, the Ia- variant B cell lymphoma cell
      line, M12.C3, expresses PBP72/74 at levels equivalent to that of the Ia+ parent
      cell line, M12.4.1, from which it was derived. Furthermore, the fibroblast L cell
      line, DAP.3, shows no cell surface expression of PBP72/74, nor do DAP.3 lines
      transfected with and expressing genes encoding the alpha- and beta-chain of the I
      Ad and I-Ed molecules. Moreover, treatment of B cells with either IL-4 or LPS,
      which increases Ia expression severalfold, does not affect PBP72/74 expression.
      Thus, PBP72/74 cell surface expression appears to be a property of B cells and
      macrophages, independent of Ia expression. In addition, the B cell surface
      expression of PBP72/74 is not altered by stress in the form of heat shock. Thus,
      PBP72/74 appears to be a constitutive noninducible member of the hsp70 family. By
      immunoelectron microscopy, PBP72/74 is detected in approximately 36% of early
      endocytic vesicles into which surface Ig is internalized after binding to anti-Ig
      antibodies. This compartment was previously shown to contain class II en route to
      the cell surface associated with invariant chain and the proteases cathepsin B
      and D and is suggested to be a subcellular site of antigen processing. PBP72/74
      is also found associated with the plasma membrane, endoplasmic reticulum, and
      membranes proximal to the Golgi stacks. The cellular and subcellular distribution
      of PBP72/74 is consistent with its playing a role in the processing of
      presentation of Ag with the MHC class II molecules.

PMID- 1987276
TI  - IL-6 production by human T lymphocytes. Expression in HTLV-1-infected but not in
      normal T cells.
AB  - IL-6 is an important regulator of humoral and cellular immunity. Although this
      cytokine is produced by diverse cell types, it is not known whether it is
      produced by T lymphocytes under physiologic conditions or which agents can induce
      T cell expression of IL-6. We analyzed the production of IL-6 by human peripheral
      blood T cells, human thymocytes, and human T cell lines. In pure populations of
      these cells, stimulated with different combinations of various mitogens and
      cytokines, IL-6 activity could not be detected. Analysis of purified T-alpha beta
      and T-gamma delta cells showed that neither T cell subset produced IL-6.
      Similarly, IL-6 mRNA was not detected in T cell or thymocyte populations for up
      to 48 h after stimulation. With the use of a PCR assay, IL-6 mRNA in T cells was
      found to be virtually negligible, and did not change after T cell activation. By
      in situ hybridization it was shown that the cells expressing IL-6 mRNA after
      mitogen activation of PBMC do not belong to the T cell lineage. To analyze
      whether human T cells express IL-6 in vivo, we examined lymphoid tissues by in
      situ hybridization. In normal human thymus there was no detectable signal for IL
      6. Tonsils showed only few positive cells within the parenchyma, but strong
      expression of IL-6 by epithelial cells in crypts. In contrast to normal lymph
      node, which contained only rare cells positive for IL-6, a lymph node from a
      patient with Castleman's disease showed IL-6 expression in cells occupying the
      marginal sinus and interfollicular areas. Screening of various human T cell lines
      showed that all cell lines infected with HTLV-1 secrete IL-6 activity and express
      IL-6 mRNA. In addition, in vitro infection of peripheral blood T cells with HTLV
      1 induced de novo synthesis and secretion of IL-6. Furthermore, IL-6 expression
      in HTLV-1-infected cells was enhanced by stimulation with IL-1 beta or TNF-alpha.
      In contrast, IL-6 was not detectable in non-infected T cell lines. These studies
      indicate that IL-6 may not be a physiologic product of human T lymphocytes and
      that infection of T cells with HTLV-1 results in aberrant expression of this
      cytokine.

PMID- 1987277
TI  - IL-1 gene expression in lymphoid tissues.
AB  - We examined the expression of IL-1 mRNA in vivo by in situ hybridization. RNA
      probes for murine IL-1 alpha and IL-1 beta were used to detect IL-1 mRNA in
      frozen sections of spleen, lymph node, and thymus of mice injected with
      Salmonella typhi LPS or SRBC. No IL-1 was detected in lymphoid tissues from un
      injected mice. This lack of expression correlated with the absence of IL-1
      biologic activity. However, after LPS injection, IL-1 alpha and beta mRNA
      expression was found in macrophages of the red pulp and marginal zone of the
      spleen. The periarteriolar lymphoid sheath contained cells that only expressed IL
      1 beta mRNA. These cells were not lymphocytes and did not stain with the
      macrophage marker F4/80. A similar cellular response was found after SRBC
      injection. Scattered macrophages in lymph nodes and thymus were positive, but
      only after LPS or SRBC injection. The spleens of mice injected with LPS had
      megakaryocytes containing IL-1 mRNA.

PMID- 1987280
TI  - Monoclonal antibodies as probes to investigate the molecular changes of C5
      associated with the different stability of the molecule on sheep erythrocytes and
      Escherichia coli 0111:B4.
AB  - The fifth C component (C5) exhibits a different stability when bound to sheep E
      or Escherichia coli 0111:B4, being fairly stable on the bacterial intermediate
      sensitized E. coli 0111:B4 coated with C components up to C5 (BAC1-5) and
      extremely labile on the RBC intermediate sensitized sheep E coated with C
      components up to C5 (EAC1-5). We examined the possibility that molecular changes
      of membrane-bound C5 might be responsible for the different functional behavior
      of the two intermediates using mAb to C5 and sensitive immunoassays to detect
      bound C5. The decay of EAC1-5 over 30 min of incubation at 37 degrees C was
      associated with a significant drop in the reactivity of bound C5 with three of
      four mAb used. These results contrasted with those obtained with BAC1-5, which
      showed unchanged reactivity with all mAb tested over the same period of
      incubation. The effect of mAb on the activity of C5 was then investigated in an
      attempt to relate the change of the reactivity pattern of EAC1-5 with the
      functional modification of bound C5. MAb 1.5 and 1.6 were the only antibodies
      that interfered with the functional activity of C5, although through a different
      mechanism. In particular, mAb 1.5 was active both on fluid-phase and on membrane
      bound C5 and is therefore likely to interact with the binding site for the late
      components on C5. Conversely, mAb 1.6 was only effective on fluid-phase C5 and
      acted by promoting a decay of BAC1-5 similar to the spontaneous decay of EAC1-5.
      We suggest that the bacterial outer membrane may protect C5 from functional decay
      and that mAb 1.6 interferes with the stabilizing effect of the bacteria in an as
      yet unclear manner.

PMID- 1987278
TI  - Effects of site-specific mutations on biologic activities of recombinant human IL
      6.
AB  - To examine structure-activity relationships of human IL-6, we have determined the
      effects of specific mutations on the biologic activity of a human rIL-6 expressed
      in bacteria. Three types of mutants were examined: 1) a variant that contains
      serines in place of the four naturally occurring cysteines; 2) a series of
      cysteine-containing deletion mutants, each having a single internal 20 amino acid
      deletion; and 3) a cysteine-free variant containing a single 20 amino acid
      deletion. The mutants of the second type constitute a set of nonoverlapping,
      adjacent deletions spanning amino acids 4 through 183 of the 184 amino acids in
      natural human IL-6. All of the mutants were expressed, along with the full
      length, cysteine-containing analogue, in Escherichia coli as fusion proteins,
      joined to beta-galactosidase through a collagen linker. This system allows
      microgram quantities of the rIL-6 variants to be partially purified from small
      bacterial cultures without chromatographic or refolding steps. Each of the rIL-6
      variants was released from the beta-galactosidase fusion protein with
      collagenase, and the recovered rIL-6 was quantitated by laser densitometry of
      Coomassie-stained, SDS polyacrylamide gels. The sp. ac. of each of the rIL-6
      variants was determined using four assays: induction of IgM secretion from an EBV
      transformed human B cell line, induction of fibrinogen secretion from a human
      hepatoma cell line, induction of fibrinogen secretion from a rat hepatoma cell
      line, and induction of proliferation of a murine hybridoma cell line. Replacement
      of cysteines with serines reduced activity relative to cysteine-containing rIL-6
      to about 20% in the rat hepatoma assay and about 3% in the mouse hybridoma assay,
      whereas activity in both of the human cell lines was reduced to less than 0.1%.
      These data suggest that the murine and rat cell lines are less selective than the
      human cell lines in their requirements for recognition of biologically active IL
      6. Each of the deletions, except that of amino acids 4 through 23, resulted in
      loss of activity in all four assays. These results suggest that the information
      necessary for activity is not contained within any one portion of the IL-6
      molecule, but rather that multiple segments of the protein are required for each
      of the biologic activities that we tested.

PMID- 1987279
TI  - Activation of human complement by IgG antisperm antibody and the demonstration of
      C3 and C5b-9-mediated immune injury to human sperm.
AB  - To investigate the role of C in the pathogenesis of antisperm antibody (ASA)
      mediated infertility, we evaluated the binding and biologic effects of antisperm
      IgG and autologous C on human sperm. A flow cytometric assay using motile sperm
      as a target for IgG ASA+ (n = 30) and ASA- (n = 5) sera was developed for the
      concomitant detection of sperm-bound IgG and the initial (C3d) and terminal (C5b
      9) C components on the surface of human sperm. Of the 30 IgG ASA+ sera evaluated
      by flow cytometry, 15 (50%) and 22 (73.3%) sera were also positive for sperm
      bound C3d and C5b-9, respectively. Monomeric IgG purified from C-fixing ASA+
      serum was able to bind to sperm and induced deposition of C3 on the sperm surface
      in the presence of human C. Incubation of motile sperm with C-fixing immune sera
      resulted in a significant loss (43 to 87%) of motility associated with
      characteristic C5b-9-induced alterations in sperm morphology leading ultimately
      to sperm lysis. When motile sperm were cocultured with purified polymorphonuclear
      leukocytes (PMN) in the presence of C-fixing immune sera, the binding of sperm
      heads to the PMN resulted in the formation of sperm rosettes, whereas non C
      fixing or control sera had no such effect. Transmission electron microscopy of
      thin sections of the rosettes revealed ingestion of the sperm by the human PMN.
      These data suggested that 1) antibody bound to sperm is capable of activating
      autologous C by the classical pathway; 2) binding of both IgG and C proteins
      initiates C3-mediated sperm binding to PMN and sperm inactivation by deposition
      of membrane attack complex (MC5b-9) of C; and 3) concomitant detection of sperm
      bound IgG, C3d, and C5b-9 may serve as an indicator of C-fixing cytotoxic ASA in
      the sera of infertile couples.

PMID- 1987281
TI  - Clonotypic analysis of anti-acetylcholine receptor antibodies from experimental
      autoimmune myasthenia gravis-sensitive Lewis rats and experimental autoimmune
      myasthenia gravis-resistant Wistar Furth rats.
AB  - A single immunization of Lewis rats with purified acetylcholine receptor (AChR)
      emulsified in adjuvant typically stimulates the production of oligoclonal AChR
      reactive antibodies (as demonstrated by IEF) dominated by the IgG2a subclass, of
      moderate but clonotypically heterogeneous relative Ag-binding avidity, and
      capable of inducing symptoms of experimental autoimmune myasthenia gravis.
      Although similar immunization of Wistar Furth rats produces AChR-reactive
      antibodies with similar characteristics of clonotypic heterogeneity, avidity, and
      isotype expression, no detectable signs of AChR-dependent muscle impairment is
      observed. This contrasts the ability to induce impaired AChR function upon the
      passive transfer of pre-formed Lewis anti-AChR antibodies into naive Wistar Furth
      rats, suggesting that disease resistance in this model is not conferred at the
      level of the AChR itself. Moreover, if more aggressive immunization protocols are
      used (i.e., multiple injections of AChR), a transient breakthrough of AChR
      dependent muscle dysfunction can be induced directly in the Wistar Furth strain
      indicating that the potential for the production of disease-causing antibodies
      does exist in the Wistar Furth repertoire. IEF analysis of Wistar Furth anti-AChR
      antibodies has revealed that hyperimmunization results in modified antibody
      clonotype expression that might explain changing expression of disease symptoms;
      however, explanations for the apparent "resistance" of Wistar Furth rats to
      disease induction are likely to be complex.

PMID- 1987282
TI  - Expression of src family genes during monocytic differentiation of HL-60 cells.
AB  - It has been reported that src family protein-tyrosine kinases were expressed
      specifically in a certain lineage or differentiation stage of hematopoietic
      cells. To understand the molecular basis for differentiation and function of
      monocyte/macrophage, we investigated the expressions of src family genes by the
      HL-60 cells stimulated with differentiation-inducing agents. TPA and vitamin D3
      (D3) were used as stimulants for monocytic development, since each agent has been
      known to induce phenotypically specific differentiation of HL-60 cells. The fyn,
      fgr, and lyn genes were characteristically expressed concomitantly with
      phenotypic changes and expressions of nuclear proto-oncogenes, whereas src, lck,
      hck, and yes genes were not. In TPA-induced differentiation of HL-60 cells, both
      fyn and lyn genes, but not fgr gene, were expressed. In contrast, both fgr and
      lyn genes, but not fyn gene, were expressed in D3-induced differentiation of the
      cells. The independent and characteristic expressions of these genes were
      observed in the further advanced differentiation of HL-60 cells induced by TPA
      plus D3 or D3 plus human transforming growth factor-beta 1. The granulocytic
      differentiation of the cells treated with retinoic acid was accompanied by
      intense expression of fgr, but weak or no expression of lyn and fyn gene. These
      data indicate that each protein-tyrosine kinase encoded by src family genes may
      play distinct roles in development and/or functions of monocyte/macrophage
      lineage cells.

PMID- 1987283
TI  - Neutrophil adhesion to xenogeneic endothelium via iC3b.
AB  - Neutrophils are thought to play an important role in the pathogenesis of
      hyperacute rejection, a dramatic form of tissue injury caused by the reaction of
      antigraft antibodies with endothelial cells of an organ allograft or xenograft.
      We asked whether the interactions of human polymorphonuclear leucocytes (PMN)
      with xenogeneic endothelium might be promoted by the binding of natural anti
      endothelial antibodies and complement by using porcine aortic endothelial cells
      (PAEC), human serum, and human PMN in an in vitro model of hyperacute rejection.
      Pretreatment of PAEC with 10% human serum followed by washing markedly increased
      PMN adhesion from 15.7 +/- 1.8% to 62.5 +/- 3.6% (p less than 0.001). Complement
      and anti-endothelial antibodies were necessary for the increase, because heat
      inactivated serum or serum depleted of IgM did not significantly increase PMN
      adhesion to treated endothelium. The induction of increased PMN adhesion to PAEC
      by human serum was observed within 1 min. The essential role of complement was
      defined using complement-depleted serum. Ten percent C2-deficient serum did not
      increase PMN adhesion whereas 10% C5-depleted or 10% C8-depleted serum caused the
      same increase in PMN adhesion as observed with normal human serum. These results
      suggested that C3 might play a critical role in enhanced neutrophil adhesion. In
      fact, PAEC treated with 10% human serum for 15 min and incubated with an F(ab')2
      antihuman C3 for 10 min completely abolished the enhanced adhesion. PAEC treated
      with 10% human serum or C5-depleted serum displayed fluorescence of iC3b whereas
      monolayers treated with heat-inactivated serum or C2-deficient serum were non
      reactive. The enhanced PMN adhesion to serum-treated PAEC was mediated through
      neutrophil receptors binding iC3b because mAb directed against CD11b/CD18
      inhibited the serum-enhanced adhesion of PMN. We conclude that PMN adhesion to
      endothelium can be significantly enhanced by the endothelial deposition of iC3b.

PMID- 1987285
TI  - Abnormalities in epidermal lipid metabolism in patients with atopic dermatitis.
AB  - Atopic dermatitis is an inflammatory skin disease characterized by dryness and
      itch of the skin. In this study, we measured the phospholipid content and the
      fatty acid pattern of lesional and lesion-free epidermal keratome biopsies on 15
      patients. For comparison, epidermal biopsies were obtained from healthy
      individuals undergoing plastic surgery. The phospholipid content of atopic
      epidermis was nearly twice as high as in healthy epidermis. Monounsaturated fatty
      acids in the phosphoglycerides were significantly increased (p less than 0.001)
      and n-6 fatty acids were significantly decreased (p less than 0.001) in lesional
      atopic epidermis compared to lesion-free epidermis. The content of esterified
      arachidonic acid in phosphatidylcholine from lesional epidermis was only 49% of
      that found in healthy epidermis (p less than 0.001). The content of free
      arachidonic acid was 47% higher (p less than 0.05), whereas the content of free
      long-chain saturated fatty acids was decreased by 29% (p less than 0.01), in
      lesional compared to lesion-free atopic epidermis. The disease severity,
      calculated as an arbitrary index, correlated inversely with the n-6 fatty acid
      content of lesion-free atopic epidermis (r = -0.89, p less than 0.001). Our
      findings suggest that atopic epidermis is characterized by an increased activity
      of phospholipase A2 and an incomplete transformation of phospholipids into other
      lipid classes.

PMID- 1987284
TI  - Tumor necrosis factor-independent IL-6 production during murine listeriosis.
AB  - We report that TNF, IL-6, and IFN-alpha/beta are produced by mice during either
      sublethal or lethal Listeria monocytogenes infections. The quantities of these
      cytokines in infected spleens increase and decrease in concordance with bacterial
      numbers in these organs. While all of these cytokines were present in Listeria
      infected spleens, only IL-6 and IFN-alpha/beta were found in the peripheral
      circulation. Inasmuch as TNF has been reported to be responsible for the
      production of IL-6 in vivo following the inoculation of a lethal dose of the Gram
      negative bacterium, Escherichia coli (Fong et al., 1989. J. Exp. Med. 170: 1627),
      experiments were undertaken to determine whether IL-6 production elicited by the
      Gram-positive bacterium, L. monocytogenes, was also TNF-dependent. It was found
      that the passive immunization of mice with neutralizing antibodies specific for
      TNF shortly before i.v. injection of a lethal or sublethal Listeria inoculum
      resulted in the complete neutralization of endogenously produced TNF, and in the
      progressive multiplication of bacteria in infected organs. It was also found that
      the anti-TNF IgG treatment resulted in a progressive increase in the amounts of
      Listeria-induced IL-6 present in spleen and blood, until the death of the host.
      These findings indicate that Listeria-induced IL-6 production in mice occurs
      primarily through a TNF-independent pathway, and correlates directly with the
      severity of the infection.

PMID- 1987286
TI  - Inositol phosphate formation in the human squamous cell carcinoma line SCC-12 F:
      studies with bradykinin, the calcium ionophore A23187, and sodium fluoride.
AB  - The phospholipase C (PLC)-mediated hydrolysis of membrane phosphoinositides is an
      important signal transduction pathway coupled to the cell-surface receptors for
      several hormones and growth factors. In addition, PLC activity can be modulated
      by changes in intracellular calcium and activation of GTP binding proteins. In
      this report, differential activation of PLC in the human keratinocyte cell line
      SCC-12F was studied as judged by specific patterns of inositol phosphate
      formation. Several hormones and growth factors previously shown to stimulate PLC
      in a variety of cell types were screened for activity in SCC-12F cells. Only
      bradykinin was active, stimulating the PLC-dependent generation of inositol
      (1,4,5) triphosphate (Ins(1,4,5)P3). Ins(1,4,5)P3 was rapidly metabolized to
      inositol(1,4)biphosphate (Ins(1,4)P2) and inositol(1,3,4,5)tetrakisphosphate
      (Ins(1,3,4,5)P4), and subsequently degraded to inositol monophosphates. The
      response elicited by bradykinin was concentration dependent (EC50 value of 50
      nM), suggesting involvement of a specific bradykinin receptor. Treatment of these
      cells with the calcium ionophore A23187 appeared to result in the direct
      formation of Ins(1,4)P2 without Ins(1,4,5)P3 as precursor. Treatment of the cells
      with AIF4-, a putative activator of GTP binding proteins, resulted in the
      generation of inositol monophosphates as the major metabolites in the absence of
      detectable Ins(1,4,5)P3 formation. Taken together, these observations suggest
      that the PLC complex present in SCC-12F cells can be differentially activated to
      yield either Ins(1,4,5)P3, Ins(1,4)P2, or InsP. The observed effects may be due
      to a direct PLC-dependent hydrolysis of the appropriate membrane
      phosphoinositide.

PMID- 1987287
TI  - Lipid content and water permeability of skin and oral mucosa.
AB  - It has been claimed that total lipid content may be the critical factor
      determining the water permeability of skin. The present study examined this
      relationship in various oral epithelia and epidermis. Epithelia was heat
      separated from specimens of porcine skin, gingiva, buccal mucosa, palate, and
      floor of mouth. Lipids were solvent extracted and separated by thin layer
      chromatography with appropriate standards. The plates were sprayed with sulfuric
      acid and charred, and the concentration of lipids was determined by densitometry
      as mg lipid/gm tissue dry weight. Permeability constants were determined for each
      tissue by using tritiated water in perfusion chambers. When these values were
      compared over all regions, total lipid did not appear to be related to the
      permeability of these tissues. However, in the keratinized regions (epidermis,
      gingiva, and palate) a lower water permeability was related to a greater content
      of total lipid, nonpolar lipid, ceramide, and glucosylceramide. In non
      keratinized tissues, a lower permeability corresponded to increased amounts of an
      unidentified glycosylceramide. The role of lipid in the permeability barrier of
      these tissues was further demonstrated by extracting specimens of skin and oral
      mucosa with chloroform/methanol and then determining Kp values; in both tissue
      regions, there was a significant increase in water permeability. Thus, although
      lipid is a component of the water permeability barrier in both skin and oral
      mucosa, different lipid components subserve this function in keratinized and non
      keratinized tissues.

PMID- 1987288
TI  - Lysis of keratinocytes by IL-2-activated peripheral blood lymphocytes.
AB  - Interleukin 2 (IL-2)-activated peripheral blood mononuclear cells (PBMC) have
      been reported to lyse tumor cells while essentially sparing normal cells in
      vitro. This report concerns IL-2-induced anti-keratinocyte (anti-KC) cytotoxic
      effectors that lyse normal human keratinocytes (KC) in vitro. Effectors were
      generated by culturing PBMC for 1-8 d in various concentrations of recombinant IL
      2 and then assayed against 51Cr-labeled targets. Effectors stimulated with 10(3)
      U/ml of IL-2 for 8 d readily lysed adherent or trypsinized autologous or
      allogeneic KC cultured in serum-free medium. Induction of anti-KC effectors was
      IL-2 dose-dependent, with as little as 12-25 U/ml of IL-2 inducing increased anti
      KC activity after 24 h of treatment. Although anti-KC activity was increased
      after overnight culture in IL-2, maximal effector potency in terms of lytic units
      (LU) per 10(6) effector cells required 4 d of IL-2 treatment. Maximal effector
      yield in terms of LU per input PBMC occurred after 8 d of IL-2 treatment.
      Antibody plus complement depletion studies showed that the anti-KC effectors
      predominantly have a CD16 --/CD3 --/CD2+ phenotype. A natural killer (NK)-like
      specificity of the effectors was suggested by two findings: unlabeled K562 cells
      totally inhibited lysis of 51Cr-KC in cold target competition assays, and
      interferon gamma (IFN-g) treatment (2.5 U/ml-500 U/ml of recombinant IFN-g for 48
      72 h) down-regulated KC susceptibility to lysis by these effectors. Thus, IL-2
      treatment of PBMC induces non-T cell, natural killer-like effectors that can lyse
      both autologous and allogeneic KC. Furthermore, KC resemble other cell types that
      become resistant to non-MHC-restricted lysis after treatment with IFN-g. Finally,
      the contrasting effects of IFN-g treatment on KC lysis by these effectors, as
      opposed to lysis by specific T cells, suggests that IFN-g could promote a shift
      from non-MHC-restricted to MHC-restricted KC lysis during epidermal immune
      responses in vivo.

PMID- 1987289
TI  - Characterization of 230-kD bullous pemphigoid antigen associated with the
      detergent-insoluble fraction of cultured keratinocytes.
AB  - The 230-kD protein identified by antibodies from patients with bullous pemphigoid
      (BP) has a dual location in cultured normal human epidermal keratinocytes: part
      in a high-speed supernatant of homogenized cells and part in a particulate
      fraction, where it is resistant to extraction by non-ionic detergent or mild
      base. Antibodies were affinity purified from the particulate 230-kD BP antigen,
      which can be extracted in the presence of urea. The affinity-purified antibodies
      bind not only the cytosolic 230-kD protein, showing that it is related, if not
      identical, to the particulate form, but also produce a discontinuous granular
      pattern by indirect immunofluorescence in the basement membrane zone of rabbit
      esophagus. In stratifying epidermal cultures, expression of the 230-kD BP antigen
      is limited to basal cells. These data are consistent with 230-kD BP antigen
      involvement in keratinocyte basal cell interaction with extracellular matrix and
      indicate that the cultured cell may provide a useful model for analysis of 230-kD
      BP antigen function.

PMID- 1987290
TI  - IgA class antibodies in dermatitis herpetiformis: reaction with tissue antigens.

PMID- 1987291
TI  - Xeroderma pigmentosum, photosensitivity, and implications for black patients.

PMID- 1987292
TI  - Characterization of skin-infiltrating lymphocytes in patients with psoriasis.
AB  - In this study, skin-infiltrating cells in psoriasis patients were characterized
      in biopsies from both involved and uninvolved skin. Histologic examination of
      biopsies showed the presence of both CD4+ and CD8+ T cells and the lack of B
      lymphocytes. Skin biopsies were also placed in tissue culture medium supplemented
      with human serum, interleukin-2 (IL-2), and irradiated autologous blood
      lymphocytes. T lymphocytes grew from both plaques and univolved skin biopsies and
      consisted of a heterogeneous population of T-cell subsets. The immunophenotypic
      analysis of cultured cells was comparable to the histologic examination on frozen
      section, i.e., there was a greater number of CD4/CDw29+ cells than CD8+/CD45+
      cells. Cultures were tested in the primed lymphocyte test (PLT) and cell-mediated
      lympholysis (CML) assays. All cultures tested demonstrated secondary
      proliferative but not cytolytic reactivity. The PLT results indicate that the
      cell cultures generated are autoreactive. This autoreactivity was found to be
      directed against non-human leukocyte antigens (HLA), i.e., minor HLA with some
      restriction to major HLA antigens.

PMID- 1987293
TI  - A clonal CD4-positive T-cell line established from the blood of a patient with
      Sezary syndrome.
AB  - The reported inability to establish long-term T-cell lines from the blood of
      cutaneous T-cell lymphoma patients with circulating neoplastic T cells has
      hindered the development of an in vitro system to investigate Sezary syndrome. We
      have established a rapidly proliferating T-cell line from the peripheral blood of
      a patient with Sezary syndrome, which expresses a mature helper T-cell phenotype
      and contains cytogenetic abnormalities and T-cell receptor gene rearrangements
      identical to those in the patient's blood. The method of establishment and
      characteristics of this line are described.

PMID- 1987294
TI  - Scanning acoustic microscopy of neoplastic and inflammatory cutaneous tissue
      specimens.
AB  - Acoustic microscopy utilizes high frequency ultrasound to generate microscopic
      images. The current study was designed to examine representative disorders of the
      skin by use of a reflective scanning acoustic microscope (R-SAM), and to
      determine whether the obtainable resolution was sufficient to render a
      microscopic diagnosis. An Olympus UH3 Scanning Acoustic Microscope was utilized
      with lenses producing burst wave frequencies at 600 and 800 MHz (600 and 800
      million cylces/sec). Cutaneous tissue specimens representing 12 different
      neoplastic and inflammatory disorders were examined. Acoustic images of unstained
      sections were compared with conventional light microscopic study of sections
      stained with hematoxylin-eosin. In most neoplasms examined, it was possible to
      make a specific diagnosis primarily from low magnification pattern analysis.
      Although individual cells could be visualized, cytologic atypia was poorly
      defined. In the inflammatory disorders, a specific diagnosis was possible in all
      but bullous pemphigoid and lichen planus, because the composition of the
      inflammatory infiltrate was difficult to determine. The advantages of the R-SAM
      include the capability of producing an acoustic profile of the tissue and the
      future possibility of in situ diagnosis.

PMID- 1987295
TI  - Oriented structure in human stratum corneum revealed by X-ray diffraction.
AB  - Various types of human stratum corneum (sheets or callus) were exposed, in
      parallel and perpendicular geometry, to the high flux of X rays produced by a
      synchrotron radiation source. Under these conditions, very clear and rich
      diffraction patterns, corresponding to the supramolecular organization of stratum
      corneum proteins and lipids, were obtained. The comparative study of normal or
      delipidized stratum corneum sheets and membrane couplets allows one to attribute
      certain diffraction features to lipids. Our results in the 3-7-nm range show two
      different distances for lipid bilayers. Concerning the protein nature of normal
      stratum corneum, the results show that keratin would occur in the beta form,
      whereas for callus it is in the alpha form. Indeed, normal stratum corneum sheets
      never display the 0.514-nm characteristic of alpha keratin. This result means
      that the supramolecular organization of keratin could depend on the
      keratinization process. Finally, our studies also confirm the presence of a still
      unknown protein component existing in the beta form that would be located either
      inside the corneocytes or in some dilatated zones of the intercellular spaces.

PMID- 1987296
TI  - T-cell subsets with a naive phenotype are selectively decreased in the peripheral
      blood of patients with mycosis fungoides.
AB  - Peripheral blood lymphocytes of 33 patients with histopathologic confirmation of
      mycosis fungoides and 27 healthy controls matched for age and sex were analyzed
      with a panel of monoclonal antibodies using both single and dual color
      immunofluorescence. Patients with mycosis fungoides had a significant reduction
      in the percentage of circulating T cells with a naive phenotype (i.e., CD4+2H4+
      and CD4+Leu8+), as well as a significant reduction in the absolute numbers of
      circulating lymphocytes with the phenotype CD8+Leu8+ compared to the control
      cohort. The reduction in circulating naive T cells was found to occur
      irrespective of stage of disease, duration of disease, or mode of treatment. The
      depletion of circulating naive T cells may reflect increased conversion to memory
      T cells in the peripheral blood or skin.

PMID- 1987297
TI  - Characterization of 5 alpha-reductase in cultured human dermal papilla cells from
      beard and occipital scalp hair.
AB  - In order to gain a deeper insight into the role of 5 alpha-reductase in the
      growth of beards in men, we studied some kinetic properties of the enzyme in cell
      homogenates of cultured human dermal papilla cells from beard and occipital scalp
      hair. When cell homogenates were incubated with [3H]-testosterone, the 5 alpha
      reductase of beard dermal papilla cells exhibited an optimum activity at pH 5.5,
      whereas the enzyme of dermal papilla cells from occipital scalp hair showed a
      broad and low plateau between pH 6.0 and 9.0, without a sharp peak. The apparent
      Michaelis constant of 5 alpha-reductase was 3.3 x 10(-7) M in dermal papilla
      cells from beard and 2.4 x 10(-5) M in those cells from occipital scalp hair. The
      apparent Km of 5 alpha-reductase for NADPH was 2.8 x 10(-5) M and 7.6 x 10(-4) M
      in beard and occipital scalp hair dermal papilla cells, respectively. There were
      no significant differences in the substrate specificity between these two types
      of cells. The 5 alpha-reductase activity was recovered mainly in the nuclear
      fraction of beard dermal papilla cells. By contrast, it was widely distributed
      among the individual subcellular fractions of dermal papilla cells from occipital
      scalp hair. These results strongly suggest that these two kinds of dermal papilla
      cells have different types of 5 alpha-reductase, and that the enzyme in beard
      dermal papilla cells is similar in characteristics to that in the androgen target
      organs such as prostate.

PMID- 1987298
TI  - Localization of minoxidil sulfotransferase in rat liver and the outer root sheath
      of anagen pelage and vibrissa follicles.
AB  - The precise biochemical mechanism and site(s) of action by which minoxidil
      stimulates hair growth are not yet clear. Minoxidil sulfate is the active
      metabolite of minoxidil, with regard to smooth muscle vasodilation and hair
      growth. Formation of minoxidil sulfate is catalyzed by specific PAPS-dependent
      sulfotransferase(s) and minoxidil-sulfating activities have been previously
      reported to be present in liver and hair follicles. One of these minoxidil
      sulfating enzymes has been purified from rat liver (rat minoxidil
      sulfotransferase, MST) and a rabbit anti-MST antibody has been prepared. Using
      this anti-MST antibody, we have immunohistochemically localized minoxidil
      sulfotransferase in the liver and anagen hair follicles from rat. In rat pelage
      and vibrissa follicles, this enzyme is localized within the cytoplasm of
      epithelial cells in the lower outer root sheath. Although the immunolocalization
      of MST might not necessarily correlate with the MST activity known to be present
      in anagen follicles, the results of this study strongly suggest that the lower
      outer root sheath of the hair follicle may serve as a site for the sulfation of
      topically applied minoxidil.

PMID- 1987299
TI  - Effects of exogenous MSH on the transformation from phaeo- to eumelanogenesis
      within C57BL/6J-Ay/a hairbulb melanocytes.
AB  - The extent to which alpha melanocyte-stimulating hormone (MSH) is a true in vivo
      regulator of melanogenesis in mice is unknown. The objective of this study was to
      determine if MSH-induced eumelanogenesis in hairbulb melanocytes of yellow (Ay/a)
      mice mimics the natural program of eumelanogenesis occurring in genetically black
      (a/a) hairbulb melanocytes. We conducted quantitative transmission electron
      microscopy on melanosome differentiation within MSH-treated regenerating 9-d
      hairbulbs of Ay/a and a/a mice. Results of exogenous alpha-MSH injections (5 d at
      0.15 mM MSH) showed that the striking visual darkening of hair was accompanied by
      an incomplete transformation of phaeo- to eumelanogenesis. Ontogenetic data on
      developmental stages I-IV of 3678 melanosomes based on geometric considerations
      (length, width, shape, and area) showed that MSH did not induce a complete
      transformation from spherical phaeomelanosomes to elliptical eumelanosomes. Also,
      observations on the number of vesiculoglobular bodies and matrix organization
      reveled that MSH-treated Ay/a melanosomes retained distinct features of
      phaeomelanogenesis even after 5 d of MSH treatment. Thus, MSH induced a partial
      but incomplete pattern of eumelanogenesis in regenerating hairbulb melanocytes of
      Ay/a mice. The continued investigation of the dynamics of melanin synthesis in
      MSH-induced Ay/a mice melanocytes possessing "mosaic" melanosomes could be
      productive in understanding fundamental relationships between tyrosinase
      activity, matrix function, matrix structure, and regulation of melanin (phaeo-
      and/or eumelanin) synthesis.

PMID- 1987300
TI  - The use of L-dopa and carbidopa in metastatic malignant melanoma.
AB  - A combination of L-dopa and carbidopa was given orally to 17 patients with
      metastatic melanoma. Maximum tolerated oral doses were given, up to 4 grams
      daily. No response was seen in 15 patients evaluable for response. Toxicity was
      considerable, with seven of 17 patients (41%) stopping treatment because of
      unacceptable gastrointestinal toxicity or postural hypotension. Contrary to
      previous anecdotal reports, there was no evidence that L-dopa/carbidopa treatment
      resulted in accelerated progression of metastatic melanoma. Orally administered L
      dopa/carbidopa is ineffective as therapy for advanced melanoma when maximum
      tolerated doses are used.

PMID- 1987301
TI  - IgA-binding structures in dermatitis herpetiformis skin are independent of
      elastic-microfibrillar bundles.
AB  - Dermatitis herpetiformis (DH) is characterized in part by the presence of
      granular deposits of IgA in the papillary dermis just beneath the dermal
      epidermal junction. The nature of the structures to which IgA binds in DH skin,
      however, has not been clearly demonstrated. Previous immunoelectron-microscopy
      studies using the peroxidase-antiperoxidase technique have concluded that the IgA
      may bind to abnormal elastic microfibrillar bundles. Recently, antibodies have
      been developed against a major component of the elastic microfibril bundles,
      fibrillin. In addition, another dermal matrix protein, hexabrachion, has been
      characterized and found in normal human skin in a distribution similar to the IgA
      deposits of DH. Utilizing antibodies against fibrillin, hexabrachion, and human
      IgA and immunoelectronmicroscopy with immunogold staining techniques, we have
      examined the skin from patients with DH in order to localize the IgA deposits.
      Normal-appearing skin from five patients with DH exhibited electron-dense patches
      within the dermis, which were not seen in skin from normal subjects. These
      structures were sometimes adjacent to the basement membrane zone, but appeared
      amorphous and without a well-defined fibrillar structure. The electron-dense
      patches were labeled with anti-human IgA, but not with antibodies to fibrillin or
      hexabrachion. The anti-IgA antibody did not label the normal basement membrane.
      These studies confirm the presence of abnormal electron-dense, amorphous
      structures in the skin of patients with DH. Due to this lack of association with
      the elastic microfibril bundles and the lack of labeling with antibodies against
      fibrillin, we suggest that these deposits are distinct from the microfibrillar
      bundles of elastic tissue and may represent IgA bound to degraded basement
      membrane or isolated dermal deposits of IgA.

PMID- 1987302
TI  - Expression of basement membrane proteins and interstitial collagens in dermal
      papillae of human hair follicles.
AB  - The expression of basement membrane molecules and interstitial collagens in human
      hair follicle mesenchyme was studied by immunohistochemical staining of tissue
      sections and of cells cultured from dermal papillae. Type I and type III
      collagens were found in the dermal sheath and in the dermal papilla throughout
      the hair cycle. Laminin and type IV collagen were expressed at the outer root
      sheath basement membrane and in the extracellular matrix of the dermal papilla of
      anagen and catagen follicles. In telogen follicles, where the volume of the
      dermal papilla extracellular matrix is much reduced, outline staining of dermal
      papilla cells for laminin and type IV collagen was still apparent. Staining for
      bullous pemphigoid antigen was also seen at the outer root sheath basement
      membrane extending to the lower tip of the hair bulb. In anagen follicles, there
      was no staining for bullous pemphigoid antigen at the interface between hair bulb
      epithelium and the dermal papilla and no staining within the dermal papilla.
      However, linear staining for bullous pemphigoid antigen became continuous around
      hair follicle epithelium during catagen and telogen. Cells cultured from human
      dermal papillae also stained for interstitial collagens, type IV collagen and
      laminin. However, similar results were obtained when cultured dermal fibroblasts
      were stained with the same antibodies. The expression of basement membrane
      proteins in human dermal papillae resembles that seen in follicles from other
      mammalian species and suggests that this is relevant to dermal papilla function.
      Cultured dermal papilla cells express a similar pattern of interstitial collagens
      and basement membrane proteins to those seen in tissue sections but this finding
      is not specific to dermal papilla cells.

PMID- 1987303
TI  - Dietary supplementation with ethyl ester concentrates of fish oil (n-3) and
      borage oil (n-6) polyunsaturated fatty acids induces epidermal generation of
      local putative anti-inflammatory metabolites.
AB  - Clinical reports have attributed the amelioration of chronic inflammatory skin
      disorders to the presence of certain polyunsaturated fatty acids (PUFA) in
      dietary oils. To test the hypothesis of a local modulatory effect of these PUFA
      in the epidermis, the basal diet of normal guinea pigs was supplemented with
      ethyl esters of either fish oil [rich in eicosapentaenoic acid (EPA) and
      docosahexaenoic acid (DHA)] or borage oil [rich in gamma-linolenic acid (GLA)].
      Our data demonstrated that dietary oils influence the distribution of PUFA in
      epidermal phospholipids and the epidermal levels of PUFA-derived hydroxy fatty
      acids. Specifically, animals supplemented with ethyl esters of fish oil markedly
      incorporated EPA and DHA into epidermal phospholipids, which paralleled the
      epidermal accumulation of 15-hydroxyeicosapentaenoic acid (15-HEPE) and 17
      hydroxydocosahexaenoic acid (17-HDoHE). Similarly, animals supplemented with
      esters of borage oil preferentially incorporated dihomogammalinolenic acid
      (DGLA), the epidermal elongase product of GLA, into the epidermal phospholipids,
      which also was accompanied by epidermal accumulation of 15-hydroxyeicosatrienoic
      acid (15-HETrE). By factoring the epidermal levels of the 15-lipoxygenase
      products and their relative inhibitory potencies, we evolved a measure of the
      overall potential of dietary oils to exert local anti-inflammatory effect. For
      example, the leukotriene inhibition potentials (LIP) of both fish oil and borage
      oil were greatly enhanced when compared to controls. Thus, the altered profiles
      of epidermal 15-lipoxygenase products generated from particular dietary oils may
      be responsible, at least in part, for reported ameliorative effects of oils on
      chronic inflammatory skin disorders.

PMID- 1987304
TI  - Hydrogen peroxide alters signal transduction in human endothelial cells.
AB  - Lytic H2O2-induced injury to human umbilical vein endothelial cells provides a
      model for endothelial cell damage in diverse states including acute respiratory
      distress and septic shock. Endothelial cell lysis is an extreme result of
      inflammatory cell activation. Functional alterations such as responsiveness to
      endothelial cell agonists and eicosanoid production might be impaired by exposure
      to inflammatory cell products including H2O2. Soluble mediators such as thrombin
      or histamine cause endothelial cell activation via a signal transduction
      mechanism that hydrolyzes phosphatidylinositol 4,5-bisphosphate (IP), liberating
      inositol trisphosphate (IP3). Accordingly, pretreatment of endothelial cells with
      H2O2 blocked the subsequent production of IP3 in response to thrombin and
      histamine. H2O2 inhibition of IP3 was time- and concentration-dependent. The
      endothelial cells were viable by trypan blue dye exclusion and chromium release.
      H2O2 inhibition of signaling was completely prevented by catalase. Iron-dependent
      oxidant radical formation appears critical because deferoxamine (10(-4) mol/L)
      pretreatment of endothelial cells prevented H2O2 inhibition of IP hydrolysis.
      Prostacyclin and platelet activating factor production in response to thrombin
      have been linked to IP hydrolysis. Pretreatment of endothelial cells with H2O2
      reduced prostacyclin and platelet-activating factor production by thrombin by at
      least 50%. It appears H2O2 can induce defects in signaling pathways with sequelae
      (decreased prostacyclin and platelet-activating factor) short of endothelial cell
      death. The possible consequences of H2O2 interaction with endothelial cells is
      reviewed with the aim of presenting a hypothesis to integrate these various
      observations.

PMID- 1987305
TI  - Intrinsic vasodilation protects Wistar Kyoto rats from progressive
      glomerulosclerosis after unilateral nephrectomy.
AB  - Genetically determined differences in functional and structural determinants that
      govern the development of progressive glomerulosclerosis (GS) were studied in
      aging sham-operated or unilaterally nephrectomized male rats of two strains.
      Wistar rats showed an increase of proteinuria and GS with age, which was enhanced
      by unilateral nephrectomy (UN). In contrast, intact and UN Wistar Kyoto rats did
      not show an increase of proteinuria with age and 7 months after UN, no GS was
      seen in these rats. Systemic blood pressure was comparable in both strains and
      was not affected by UN. Functional studies in a separate group of rats 1 month
      after UN showed an identical increase in glomerular filtration rate in both
      strains as compared with sham-operated controls. The Wistar rats did not show an
      effect of UN on renal plasma flow, and consequently, there was an increase in
      filtration fraction, in contrast to Wistar Kyoto rats, which showed an increase
      in renal plasma flow with an unchanged filtration fraction. Glomerular volume was
      increased in both strains at 1 month and 7 months after UN. Mesangial expansion
      was not observed at 1 month after UN in either strain, which indicates that this
      is not a decisive factor in the development of GS. These data indicate that the
      genetically determined susceptibility to the development of GS in these two rat
      strains may be related to the degree of vasoconstriction, whereas glomerular
      volume expansion per se does not lead to GS but can well be a consequence of
      hyperfiltration. These studies are concordant with previous studies that revealed
      the role of hemodynamics in the pathogenesis of GS irrespective of glomerular
      expansion.

PMID- 1987306
TI  - Chronic hypomagnesemia caused by cisplatin: effect of calcitriol.
AB  - A group of six patients with hypomagnesemia (serum magnesium less than or equal
      to 0.5 mmol/L), previously given treatment with cisplatin for ovarian or
      testicular cancer, received calcitriol at a dose of 0.5 to 1.0 microgram/day for
      a period of 4 weeks to determine whether treatment with this vitamin D metabolite
      could improve their hypomagnesemia. In response to treatment, the serum magnesium
      concentration fell progressively in association with a rise in serum and urinary
      calcium levels and a decrease in parathyroid hormone level. In a single previous
      report, active vitamin D metabolites markedly improved renal magnesium wasting.
      However, in the present study, increases in serum and urinary calcium levels and
      suppression of parathyroid hormone, factors known to decrease magnesium
      reabsorption, presumably overwhelmed any direct effect calcitriol may have had to
      enhance magnesium reabsorption, so that the net effect was a marked exacerbation
      of the renal magnesium wasting.

PMID- 1987307
TI  - Intrinsic differences in the filling response of the guinea pig duodenum and
      ileum.
AB  - Transit of intestinal contents differs between the duodenum and ileum in intact
      animals. To determine whether this relates to intrinsic differences in the
      capacity, distensibility, or filling response of these segments, we used the
      isolated duodenum and ileum of 13 guinea pigs to record: (1) increases in the
      diameter and luminal volume produced by specific pressure heads and (2) the
      pressure waves and movements of the segments in response to bolus injections. We
      found that the duodenum and the ileum had similar diameters in the empty state,
      and when filled with volumes below 0.4 ml both generated baseline pressures below
      3 cm H2O. However, the ileum increased its diameter and volume significantly more
      in response to increases in inflow pressure than the duodenum did. Conversely,
      injection of bolus volumes led to pressure waves of higher amplitude and longer
      duration in the duodenum than in the ileum. The pressure waves were produced by
      sharply defined ring contractions in the ileum; there was bulging of the walls
      downstream from the contraction site and collapse upstream from it. In the
      duodenum, the contraction involved a longer segment and was shallow with ill
      defined margins. These intrinsic differences in the capacity, distensibility, and
      contraction patterns of the duodenum and ileum are likely to affect luminal
      transit and other mechanical functions of these intestinal segments in the intact
      animal.

PMID- 1987308
TI  - The reproducibility and heritability of individual differences in osmoregulatory
      function in normal human subjects.
AB  - The rise in plasma vasopressin produced by infusion of hypertonic saline varies
      widely among healthy adults. To determine if these interindividual differences
      are reproducible, we used linear regression to analyze the relationship of plasma
      vasopressin to plasma osmolality during repeat hypertonic saline infusion in
      seven normal subjects. The results confirmed that the slope or sensitivity of the
      relationship differed widely between subjects (0.12 to 1.66 pg/ml/mOsm/kg) and
      revealed that these differences were highly reproducible. (r = 0.94 on repeat
      testing). The individual values for osmotic threshold were less variable (280 to
      288 mOsm/kg) as well as less clearly reproducible (r = 0.61). To determine
      whether these differences are genetically influenced, we compared the vasopressin
      osmolality relationships within seven monozygotic and six dizygotic twin pairs.
      We found that the threshold and sensitivity values correlated significantly
      within monozygotes (r = 0.95 and 0.95) but not within dizygotes (r = 0.34 and
      0.21). When the osmoregulation of thirst was similarly evaluated, the individual
      relationships were as variable as for plasma vasopressin, but only the threshold
      values in monozygotes correlated significantly (r = 0.92). In 80 healthy adults,
      the frequency distributions of the osmotic threshold and sensitivity of the
      vasopressin responses were essentially normal. We conclude that the sensitivity
      for vasopressin secretion as well as the osmotic thresholds for thirst and
      vasopressin demonstrate significant polygenetic variance among healthy adults.

PMID- 1987309
TI  - Oxidative insults: sublethal injury to the endothelium by H2O2.

PMID- 1987310
TI  - Morphology of sickle cells produced in solutions of varying osmolarities.
AB  - The effect of varying osmolarities (0.6% to 1.5% NaCl solutions, 213 to 492
      mOsm/kg H2O) on the morphology of deoxygenated sickle cells was studied
      quantitatively with a computer-assisted image analysis system. Discocyte-rich,
      less dense fractions of sickle cells (density less than or equal to 1.11) were
      suspended in buffered NaCl solutions (pH 7.4) of various osmolarities,
      deoxygenated at room temperature for up to 5 hours, and stained by Wright's
      solution. Microscopic images were analyzed by circular shape factor (CSF = 4 pi x
      [area]/[perimeter]2) and elliptical shape factor (ESF = [short axis]/[long
      axis]). Since these two parameters yield different values for elongated cells and
      for cells of other shapes, such as maple-leaf- or star-shaped cells, the
      morphologic changes of sickle cells can be analyzed numerically. We found that
      both the rate and the degree of deformation depended highly on the osmotic
      pressure of the media in which the cells were suspended. In hypertonic solution,
      most sickle cells assumed a maple-leaf shape. The deformation occurred quickly,
      but the degree of deformation (circular shape factor and elliptical shape factor)
      was lower than that found in isotonic and slightly hypotonic solutions. Although
      elongated cells were formed in hypotonic and isotonic solutions, deformation was
      slower in these solutions than in hypertonic solutions. These results indicate
      that the shape and the degree of deformation of deoxygenated sickle cells are
      highly dependent on the osmolarity of the suspending medium and that the rate of
      deformation is inversely related to osmolarity. The relationship between
      morphology of deoxygenated sickle cells and osmotic pressure of the suspending
      media is discussed.

PMID- 1987311
TI  - Plasma glucagon concentration in cirrhosis is related to liver function but not
      to portal-systemic shunting, systemic vascular resistance, or urinary sodium
      excretion.
AB  - We tested the hypothesis that increased plasma glucagon concentration resulting
      from portal-systemic shunting or liver dysfunction causes arterial vasodilation
      and thereby stimulates sodium retention in cirrhosis. Twenty-seven studies were
      performed in patients with alcoholic liver disease, 11 of whom had ascites. Liver
      function was quantitated as the elimination rate of antipyrine, caffeine, and
      stable isotopes of cholic acid administered both orally (2,2,4,4-2H) and
      intravenously (24-13C). Portal-systemic shunt fraction was calculated as the
      ratio of the intravenous and oral clearances of the isotopes of cholic acid.
      Cardiac output was measured by using Doppler echocardiography. Plasma glucagon
      concentration was increased in patients with ascites when compared with that in
      patients without ascites (474 +/- 180 pg/ml vs 245 +/- 120 pg/ml, p = 0.0007) but
      was unrelated to urinary sodium excretion, heart rate, mean arterial pressure,
      cardiac output, and systemic vascular resistance (r = -0.48, 0.35, -0.13, 0.18,
      and 0.22, respectively). Plasma glucagon concentration correlated with the half
      lives of all model compounds (r = 0.58, p = 0.002; r = 0.62, p = 0.0008; r =
      0.62, p = 0.001; and r = 0.64, p = 0.0005; for caffeine, antipyrine, oral and
      intravenous cholic acid, respectively) but not with shunt fraction (r = 0.14).
      Increased plasma glucagon concentration in cirrhosis is probably a result of
      diminished hepatic clearance. However, increased plasma concentration of glucagon
      does not appear to cause a hyperdynamic circulatory state or sodium retention.

PMID- 1987312
TI  - Fibrinolysis, thrombocytopenia, and coagulation abnormalities complicating high
      dose interleukin-2 immunotherapy.
AB  - High-dose interleukin-2 (IL-2) immunotherapy can cause hypotension, respiratory
      distress, interstitial edema, and thrombocytopenia, similar to endotoxic shock.
      We have observed that IL-2 has no direct effect on coagulation factors in vitro,
      but it has been observed to alter the coagulant properties of vascular
      endothelium. Accordingly, we investigated the possibility that IL-2 infusions
      initiate plasma fibrinolysis and disseminated intravascular coagulation (DIC). We
      studied the clinical course, platelet count, and coagulation profile in response
      to IL-2 infusion in seven patients, two with metastatic melanoma and five with
      metastatic renal cell carcinoma. Every patient experienced hemodynamic
      instability and thrombocytopenia, and one patient suffered an unusual
      complication, mesenteric thrombosis. No patient had appreciable changes in the
      prothrombin time or the partial thromboplastin time, nor did factors V or VIII
      decline in the two patients observed. In four patients examined, we found
      decreased titers of Hageman factor (factor XII), high molecular weight kininogen,
      prekallikrein, and plasma thromboplastin antecedent, as if these had been
      consumed by reactions of the intrinsic pathway of thrombin formation. Circulating
      D-dimer fragments were found in the plasma of every patient at some point during
      each infusion cycle, and we observed decreased titers of plasminogen in the four
      patients just mentioned, suggesting that IL-2 infusions initiated fibrinolysis.
      Taken together, the clotting factor derangements and related toxicity phenomena
      cannot be ascribed firmly to DIC. Activation of the intrinsic (contact) system of
      coagulation, however, may provide one link between the vascular endothelial
      surface alterations caused by IL-2 infusions and the development of the systemic
      toxicity that resembles septic shock.

PMID- 1987313
TI  - Dalton's cat: a bridge between laboratory and clinic.

PMID- 1987314
TI  - Histochemical study of aldehyde dehydrogenase in the rat CNS.
AB  - A quantitative histochemical method was developed to determine aldehyde
      dehydrogenase (EC 1.2.1.3; ALDH) activity in the CNS. The distribution of ALDH
      activity in all rat brain and spinal cord regions is described. Among the CNS
      neuron structures, high enzyme activity was found in receptor and effector
      neurons, whereas low activity was noted in perikarya of the majority of
      intermediate neurons, including all aminergic neurons. A positive correlation was
      demonstrated between the distribution of ALDH activity among rat CNS microregions
      (our own data) and the density of dopaminergic terminals, dopamine content, and
      monoamine oxidase activity (literature data) among the same microregions. They
      may reflect a spatial linkage between ALDH and the predicted sites of natural
      aldehyde production. Lower enzyme activity was found in phylogenetically younger
      brain structures. It may explain the differential resistance of CNS structures to
      ethanol (acetaldehyde). Among the barrier CNS structures, moderate ALDH activity
      was found in capillaries and surrounding astrocytes and high activity was noted
      in ependimocytes covering the brain cavities and those of the vascular plexus.
      This provides realization of the function of ALDH as a brain metabolic barrier
      for aldehydes.

PMID- 1987315
TI  - Purification, characterization, and localization of aspartoacylase from bovine
      brain.
AB  - Canavan disease, an autosomal recessive disorder, is characterized biochemically
      by N-acetylaspartic aciduria and aspartoacylase (N-acyl-L-aspartate
      amidohydrolase; EC 3.5.1.15) deficiency. However, the role of aspartoacylase and
      N-acetylaspartic acid in brain metabolism is unknown. Aspartoacylase has been
      purified to apparent homogeneity with a specific activity of approximately 19,000
      20,000 nmol of aspartate released/mg of protein. The native enzyme is a 58-kDa
      monomer. The purified aspartoacylase activity is enhanced by divalent cations,
      nonionic detergents, and dithiothreitol. Low levels of dithiothreitol or beta
      mercaptoethanol are required for enzyme stability. Aspartoacylase has a Km of 8.5
      x 10(-4) M and a Vmax of 43,000 nmol/min/mg of protein. Inhibition of
      aspartoacylase by glycyl-L-aspartate and amino derivatives of D-aspartic acid
      suggests that the carbon backbone of the substrate is primarily involved in its
      interaction with the active site and that a blocked amino group is essential for
      the catalytic activity of aspartoacylase. Biochemical and immunocytochemical
      studies revealed that aspartoacylase is localized to white matter, whereas the N
      acetylaspartic acid concentration is threefold higher in gray matter than in
      white matter. Our studies so far indicate that aspartoacylase is conserved across
      species during evolution and suggest a significant role for aspartoacylase and N
      acetylaspartic acid in normal brain biology.

PMID- 1987316
TI  - Soluble 5'-nucleotidase activities in rat brain.
AB  - 5'-Nucleotidase activity was assayed in 105,000-g supernatants from rat brain by
      following conversion of [3H]AMP into adenosine. The effect of ATP on this process
      was complex and suggested the presence of at least two soluble 5'-nucleotidase
      activities: one inhibited by ATP and another activated by ATP. The relative
      proportions of these activities differed considerably among brain regions.
      Activity changes induced by hypothyroidism also suggested that these activities
      may be regulated independently. These findings may have consequences for the
      regional regulation of adenosine formation in the brain.

PMID- 1987317
TI  - Serotonin synthesis rate measured in living dog brain by positron emission
      tomography.
AB  - In vivo measurements by positron emission tomography of the brain serotonin
      synthesis rates in the normal dog, in the dog with increased plasma tryptophan
      concentration, and in the dog under different arterial oxygen tensions are
      described. The method described here permits repeated measurements in the same
      brain for the first time. An increase in the plasma tryptophan concentration from
      16.6 to 191.5 and then to 381 microM resulted in close to a linear increase in
      the brain serotonin synthesis rate. When PaO2 was raised from 76 +/- 2 to 106 +/-
      1 mm Hg, the rate of serotonin synthesis in the dog brain increased from 39 +/- 8
      to 54 +/- 10 pmol g-1 min-1. The estimates of the Michaelis-Menten constants,
      Kappm and Vmax, for the transport of tryptophan through the blood-brain barrier
      are 303 +/- 54 microM and 63 +/- 10 nmol g-1 min-1, respectively.

PMID- 1987319
TI  - The fusion of liposomes to rat brain microsomal membranes regulates
      phosphatidylserine synthesis.
AB  - Rat brain microsomal membranes were fused to liposomes prepared with several pure
      lipids, namely, phosphatidylserine, phosphatidylinositol, phosphatidic acid, and
      mixtures of phosphatidic acid and phosphatidylcholine or
      phosphatidylethanolamine. The fusion between liposomes and microsomes was
      measured by the octadecyl rhodamine B chloride method. The extent and other
      properties of fusion largely depend on the lipid used to prepare liposomes;
      phosphatidic acid and phosphatidylinositol fuse more extensively than other lipid
      classes. The activity of serine base exchange is affected by the fusion between
      rat brain microsomes and lipids. It is strongly inhibited by phosphatidylserine,
      but it is activated by phosphatidic acid. The inhibition produced by
      phosphatidylserine on its own synthesis is proposed as a mechanism for
      controlling the formation of phosphatidylserine in rat brain microsomes.

PMID- 1987318
TI  - The dopamine transporter is absent in parkinsonian putamen and reduced in the
      caudate nucleus.
AB  - The neuronal dopamine transporter/uptake site can be covalently labeled with the
      photoaffinity probe 1-(2-[bis-(4-fluorophenyl) methoxy]ethyl)-4-[2-(4-azido-3
      [125I]iodophenyl)ethyl]piperazine [( 125I]FAPP) and visualized following sodium
      dodecyl sulfate polyacrylamide gel electrophoresis and autoradiography. Upon
      photolysis, [125I]FAPP specifically incorporated into a polypeptide of apparent
      Mr = 62,000 in membranes from both the putamen and the caudate nucleus of
      control, Alzheimer's, schizophrenia, and Huntington's diseased brain, and
      following complete deglycosylation, migrated as an Mr approximately 48,000
      polypeptide. In parkinsonian postmortem putamen, however, there was no detectable
      photoincorporation of [125I]FAPP into the ligand binding subunit of the dopamine
      transporter. [125I]FAPP did specifically label the Mr 62,000 polypeptide of
      parkinsonian caudate, although with efficiencies of 20-50% of control. The
      asymmetrical loss of the dopamine transporter in Parkinson's diseased striatum
      was confirmed in reversible receptor binding experiments using [3H]GBR-12935 (3H
      labeled 1-[2-(diphenylmethoxy) ethyl]-4-(3-phenylpropyl)piperazine). In
      parkinsonian putamen, mazindol competitively inhibited the binding of [3H]GBR
      12935 with an estimated affinity (Ki approximately 2,000 nM) 10 times lower than
      in controls (Ki approximately 30 nM), while the affinity of maxindol for [3H]GBR
      12935 binding in the caudate was equal to that seen with controls (Ki
      approximately 50 nM). The proportion of [3H]GBR-12935 binding sites recognized by
      mazindol with high affinity in Parkinson's diseased caudate was, however, reduced
      by 50-80%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1987320
TI  - Inhibitors of urokinase and thrombin in cultured neural cells.
AB  - Recent studies have suggested important roles for certain proteases and protease
      inhibitors in the growth and development of the CNS. In the present studies,
      inhibitors of urokinase or thrombin in cultured neural cells and serum-free
      medium from the cells were identified by screening for components that formed
      sodium dodecyl sulfate-stable complexes with 125I-urokinase or 125I-thrombin.
      Rinsed glioblastoma possessed two components that complexed 125I-urokinase. One
      was type 1 plasminogen activator inhibitor (PAI-1), because the 125I-urokinase
      containing complexes were immunoprecipitated with anti-PAI-1 antibodies. The
      other component formed complexes with 125I-urokinase that were not recognized by
      antibodies to PAI-1 or protease nexin-1 (PN-1). Its identity is unknown. In
      addition to these cell-bound components, the glioblastoma cells also secreted two
      inhibitors that formed complexes with 125I-urokinase; one was PAI-1, and the
      other was PN-1. The secreted PN-1 also formed complexes with 125I-thrombin. It
      was the only thrombin inhibitor detected in these studies. Human neuroblastoma
      cells did not contain components that formed detectable complexes with either
      125I-urokinase or 125I-thrombin. However, human neuroblastoma cells did contain
      very low levels of PN-1 mRNA and PN-1 protein. Added PN-1 bound to the surface of
      both glioblastoma and neuroblastoma cells. This interaction accelerated the
      inhibition of thrombin by PN-1 and blocked the ability of PN-1 to form complexes
      with 125I-urokinase. Thus, cell-bound PN-1 was a specific thrombin
      inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1987321
TI  - Calcium-independent gamma-aminobutyric acid release from growth cones: role of
      gamma-aminobutyric acid transport.
AB  - Neuronal growth cones isolated in bulk from neonatal rat forebrain have uptake
      and K(+)-stimulated release mechanisms for gamma-aminobutyric acid (GABA). Up to
      and including postnatal day 5, the K(+)-stimulated release of [3H]GABA and
      endogenous GABA is Ca2+ independent. At these ages, isolated growth cones neither
      contain synaptic vesicles nor stain for synaptic vesicle antigens. Here we
      examined the possibility that the release mechanism underlying Ca2(+)-independent
      GABA release from isolated growth cones is by reversal of the plasma membrane
      GABA transporter. The effects of two GABA transporter inhibitors, nipecotic acid
      and an analogue of nipecotic acid, SKF 89976-A, on K(+)-stimulated release of
      [3H]GABA from superfused growth cones were examined. Nipecotic acid both
      stimulated basal [3H]GABA release and enhanced K(+)-stimulated release of
      [3H]GABA, which indicates that this agent can stimulate GABA release and is,
      therefore, not a useful inhibitor with which to test the role of the GABA
      transporter in K(+)-stimulated GABA release from growth cones. In contrast, SKF
      89976-A profoundly depressed both basal and K(+)-stimulated [3H]GABA release.
      This occurred at similar concentrations at which uptake was blocked. These
      observations provide evidence for a major role of the GABA transporter in GABA
      release from neuronal growth cones.

PMID- 1987322
TI  - Recovery of postischemic brain metabolism and function following treatment with a
      free radical scavenger and platelet-activating factor antagonists.
AB  - We have studied the metabolic and functional effects of two new platelet
      activating factor (PAF) antagonists (BN 50726 and BN 50739) and their diluent
      (dimethyl sulfoxide; DMSO) during reoxygenation of the 14-min ischemic isolated
      brain. Blood gases, EEG, auditory evoked potentials, cerebral metabolic rate for
      glucose (CMRglc), and cerebral metabolic rate for oxygen (CMRO2) were monitored
      throughout the study. Frozen brain samples were taken for measurement of brain
      tissue high-energy phosphates, carbohydrate content, and thiobarbituric acid
      reactive material (TBAR, an indicator of lipid peroxidation) at the end of the
      study. Following 60 min of reoxygenation in the nontreated 14-min ischemic
      brains, lactate, AMP, creatine (Cr), intracellular hydrogen ion concentration
      [H+]i), and TBAR values were significantly higher and ATP, creatine phosphate
      (PCr), CMRglc, CMRO2, and energy charge (EC) values were significantly lower than
      the corresponding normoxic control values. PCr and CMRO2 values were
      significantly higher, and glycogen, AMP, and [H+]i values were significantly
      lower in the BN 50726-treated ischemic brains than in DMSO-treated ischemic
      brains. In brains treated with BN 50739, ATP, ADP, PCr, CMRO2, and EC values were
      significantly higher, and lactate, AMP, Cr, and [H+]i values were significantly
      lower than corresponding values in the DMSO-treated ischemic brains. TBAR values
      were near control levels in all brains exposed to DMSO. There was also marked
      recovery of EEG and auditory evoked potentials in brains treated with DMSO.
      Treatment with BN 50726 or BN 50739 in DMSO appeared to improve brain
      mitochondrial function and energy metabolism partly as the result of DMSO action
      as a free radical scavenger.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1987323
TI  - Quantitative autoradiography reveals different angiotensin II receptor subtypes
      in selected rat brain nuclei.
AB  - Heterogeneity of rat brain angiotensin II receptors was revealed by quantitative
      autoradiography after incubation with 125I-Sar1-angiotensin II and displacement
      with the angiotensin II antagonists CGP 42112 A and DuP-753 and by receptor
      sensitivity to dithiothreitol. Receptors in areas involved in cardiovascular and
      fluid control--the subfornical organ, nucleus of the solitary tract,
      paraventricular nucleus, and area postrema--are displaced by DuP-753 with an IC50
      of 1 x 10(-7) M, are sensitive to 5 mM dithiothreitol, and thus are angiotensin
      II type-1. Receptors in the inferior olive are displaced by CGP 42112 A (IC50, 1
      x 10(-9) M) but not by DuP-753 in concentrations up to 10(-4) M, are insensitive
      to 5 mM dithiothreitol, and thus are angiotensin II type-2.

PMID- 1987324
TI  - Brain histamine in rats with hepatic encephalopathy.
AB  - Chronic liver failure induced by portocaval anastomosis (PCA) in Wistar rats
      resulted in a dramatic increase in histamine concentration in hypothalamus and a
      smaller, but clearly pronounced, elevation in the rest of brain. Between 10 and
      120 days following surgery, shunted rats exhibited a histamine level 2.4- to 13
      fold higher in hypothalamus and 1.5- to 2.5-fold higher in the rest of brain as
      compared to their control, sham-operated pairs. There were no significant changes
      in histamine concentration in the other examined tissues. The increase in brain
      histamine could not be attributed to the inhibition of its degradation, because
      activity of histamine N-methyltransferase remained unchanged for at least 40
      days. Although the activity of histidine decarboxylase also remained unchanged
      when measured at a saturating concentration of L-histidine, the increase in
      histamine content in brain seems to be due to its enhanced synthesis brought
      about by increased availability of L-histidine in the tissue, as indicated by two
      to four times higher concentrations of this amino acid in PCA rats.

PMID- 1987325
TI  - Ca2+o-independent veratridine-evoked acetylcholine release from striatal slices
      is not inhibited by vesamicol (AH5183): mobilization of distinct transmitter
      pools.
AB  - The effect of 2-(4-phenylpiperidino)cyclohexanol (AH5183 or vesamicol), a
      compound known to block the uptake of acetylcholine (ACh) into cholinergic
      synaptic vesicles, on the release of endogenous and [14C]ACh from slices of rat
      striatum was investigated. ACh release was evoked either by electrical
      stimulation or by veratridine. The effect of electrical stimulation was entirely
      dependent on external Ca2+. By contrast, veratridine (40 microM) also enhanced
      ACh release in the absence of Ca2+. Indeed, with veratridine two components were
      clearly distinguished: one dependent on external Ca2+ and the other not.
      Vesamicol inhibited [14C]ACh release evoked by both veratridine and electrical
      stimulation in the presence of external Ca2+, provided it was added to the tissue
      prior to loading with [14C]choline. With the same treatment vesamicol only
      slightly affected the release of endogenous ACh. Under the same conditions the
      Ca2(+)-independent [14C]ACh release evoked by veratridine was not prevented by
      vesamicol. The differential responsiveness to vesamicol suggests that ACh pools
      involved in Ca2+o-dependent ACh release are different from those mobilized during
      Ca2+o-independent ACh release.

PMID- 1987326
TI  - Stimulation of neurite outgrowth in neuroblastoma cells by neuraminidase:
      putative role of GM1 ganglioside in differentiation.
AB  - Treatment of three neuroblastoma cell types in culture with neuraminidase
      resulted in enhanced neurite outgrowth. These included the mouse Neuro-2A and rat
      B104 and B50 lines. The morphological changes depended on the presence of
      exogenous Ca2+ and were accompanied by modest but statistically significant
      increases in 45Ca2+ influx. Neuraminidase-stimulated neuritogenesis was blocked
      by the B subunit of cholera toxin (cholera B) and anti-GM1 antibody, a finding
      suggesting the effect was due to an increased amount of GM1 on the cell surface.
      Cholera B also blocked the increase in 45Ca2+ influx. The mouse N1A-103 line,
      previously characterized as "neurite minus," did not respond to neuraminidase
      with either neurite outgrowth or enhanced Ca2+ influx. These results point to an
      influence of GM1 on neuritogenesis in cells with differentiation potential and
      suggest a mechanism involving modulation of Ca2+ flux.

PMID- 1987328
TI  - Treating hyperlipidemia.

PMID- 1987327
TI  - Debunking the cholesterol myth: scientific support from epidemiologic studies and
      clinical trials.

PMID- 1987329
TI  - An update from the National Cholesterol Education Program: implications for
      nurses.
AB  - The article presents an update of activities from the National Cholesterol
      Education Program, including information about the recently released documents
      addressing laboratory standardization for cholesterol evaluation, public
      screening for cholesterol, the panel report of dietary recommendations for the
      nation, and a description of the American Heart Association Cholesterol Education
      Program for Nurses. Implications for nursing are discussed in light of these
      releases.

PMID- 1987330
TI  - Measurement issues in cholesterol screening: an overview for nurses.
AB  - The detection of elevated cholesterol levels in more than 60% of adults in the
      United States has prompted widespread mass cholesterol screening to identify this
      modifiable risk factor for coronary disease. As nurses begin to assume more
      responsibility for these screenings, additional training in this area may be
      warranted. National screening guidelines are reviewed in reference to measurement
      issues, including potential sources of variation in cholesterol measurement,
      precision and accuracy testing, and the importance of rigorous quality control
      measures and staff training programs, all of which ensure the standardization of
      cholesterol measurements. The role of nurses in cholesterol screening is
      presented.

PMID- 1987331
TI  - Dietary management of hyperlipidemia.
AB  - The atherogenic effects of low-density lipoprotein cholesterol (LDL-C) and the
      relationship between high levels of LDL-C and coronary heart disease are well
      established. The article briefly reviews significant research that has provided
      the rationale for dietary intervention in hyperlipidemia. The focus is the
      principles of dietary treatment and their clinical application. Methods of
      counseling and instruction aimed at lowering fat, cholesterol, and calorie
      consumption and strategies to improve patient compliance are discussed.

PMID- 1987332
TI  - Pharmacotherapy for hypercholesterolemia: guidelines and nursing perspectives.
AB  - The new guidelines of the National Cholesterol Education Program (NCEP) for the
      treatment of adults with hypercholesterolemia provide a standard treatment
      algorithm for treating patients with cholesterol-lowering medications. These
      guidelines provide physicians, nurses, and patients with important answers to
      questions about beginning drug therapy, choice of an appropriate medication, and
      the proper follow-up for long-term therapy. The article provides highlights of
      the NCEP guidelines for pharmacotherapy for hypercholesterolemia; the available
      medications, their effects on blood lipids, side effects, and requirements for
      follow-up; and the important role that nurses play in medication and compliance
      counseling.

PMID- 1987333
TI  - Educational and behavioral strategies for successful cholesterol management.
AB  - Successful management of elevated cholesterol requires a change of behaviors that
      raise cholesterol and adherence to behaviors that lower it. A partnership between
      patient and provider that is characterized by mutual trust enhances
      implementation of an effective treatment plan. Educational and behavioral
      strategies can be individualized subsequent to a comprehensive assessment.
      Monitoring efforts and results provide feedback about goal attainment and
      adjustment of the plan.

PMID- 1987334
TI  - Treating hyperlipidemia.
AB  - Studies are reviewed that describe a nurse-managed clinic for treating
      hypercholesterolemia and two large drug trials that demonstrated a lowered risk
      of coronary artery disease associated with antilipid therapy.

PMID- 1987335
TI  - A nursing approach to the management of type IIA hyperlipidemia: case study of a
      young adult.
AB  - This case study illustrates the chronic nature of hyperlipidemia type IIa and the
      important contribution of the nurse in helping the client adjust life style,
      manage complex health regimes, and cope with the uncertainty of disease
      progression and its associated risks.

PMID- 1987336
TI  - Determinants of health-promoting behaviors in adults.
AB  - Risk reduction for coronary artery disease (CAD) is a goal of health providers.
      The purposes of this study were to determine: 1) adults' knowledge about CAD; 2)
      if adults who have risk for CAD also practice health-promoting behaviors; and, 3)
      if there is a correlation among adults' practice of health-promoting behaviors,
      health locus of control, value of health, and knowledge of CAD risk factors.
      Findings indicate that subjects were knowledgeable about personal CAD risk, and
      those with higher CAD risk knowledge also practiced more health-promoting
      behaviors. Subjects had less knowledge about elevated cholesterol levels,
      diabetes, and use of oral contraceptives. Additional findings suggest that
      individuals' beliefs about control over their health, health value, and knowledge
      about CAD risk factors are related to their participation in health-promoting
      behaviors.

PMID- 1987337
TI  - Creating a better work environment. Measuring effectiveness.
AB  - Strategies to improve one hospital's work environment have paid off in
      significantly improved nursing staff satisfaction. Preintervention and
      postintervention surveys using similar instruments showed gratifying improvements
      in staff satisfaction with communication with managers, recognition by managers,
      opportunities for professional growth and development, and support by peers.

PMID- 1987338
TI  - Middle nurse manager effectiveness.
AB  - In a nationwide survey of academic health center chief nurse executives (CNEs)
      and middle nurse managers (MNMs), human management skill was ranked as the most
      important criterion of effectiveness. The characteristic of
      flexibility/negotiation/compromise was second. Neither group reported fiscal
      management skills as a top priority for MNM effectiveness. The authors compare
      the results with earlier studies of the effectiveness criteria of CNEs, for whom
      human management skills were ranked second and general management skills first.

PMID- 1987339
TI  - The University Hospital Nurse Extender Model. Part I, An overview and conceptual
      framework.
AB  - The University Hospital Nurse Extender Model using patient care technicians is a
      long-term strategy to maintain quality patient care. The authors present an
      overview and conceptual framework of the model. In future papers in this four
      part series, the authors will discuss the implementation and evaluation of the
      model and describe six lessons learned during the implementation process. This
      information will be useful to any nursing administrator planning to implement a
      change in the way patient care is delivered.

PMID- 1987340
TI  - Expert nursing diagnoses. The link between nursing care plans and patient
      classification systems.
AB  - The two main tools used by the nurse in organizing and managing patient care are
      nursing care plans and the patient classification system. The author presents an
      overview of a novel approach that links these two tools through the use of expert
      nursing diagnoses and then applies the development and use of expert nursing
      diagnoses to the psychiatric setting. The author also describes the methodology
      used to develop the related patient classification, clarifies the validation
      procedure, gives examples of the final product, and considers the application and
      potential value of the total approach.

PMID- 1987341
TI  - A nurse on the board.
AB  - With increasing frequency, nurses executives are serving on corporations' boards
      of directors. Acknowledging differences in the transition from operations to
      governance, the author discusses the governance role, board functions,
      relationships between the chief executive officer and the board, and operating
      protocols.

PMID- 1987342
TI  - The ethics of information.
AB  - Information technology provides the means by which patient data can be easily
      accessed. Countering the availability trend is the need for patient
      confidentiality and privacy. The authors describe a simple survey aimed at
      investigating the improper accessing of a hospital information system. The
      results of the study provide the catalyst for a discussion of the relationships
      between information systems technology and ethical nursing behavior.

PMID- 1987344
TI  - Ethical dilemmas and conflict.

PMID- 1987343
TI  - Analyzing ethical dilemmas.

PMID- 1987345
TI  - Rational irrationality: an organization alternative.

PMID- 1987346
TI  - HIV infection in pregnancy: epidemiology and clinical management.

PMID- 1987347
TI  - HIV infection in children: clinical features and management.

PMID- 1987348
TI  - Limitations in the laboratory diagnosis of vertically acquired HIV infection.
AB  - At present, the only well-standardized and widely available diagnostic techniques
      for HIV infection are detection of IgG HIV antibodies and HIV antigen. The
      antibody detection is sensitive, but is useful only in infants and children older
      than 15 months because of the presence of maternal antibodies. The utility of HIV
      antigen testing in neonates and young infants has not been established. A number
      of sensitive techniques, such as PCR, ELISPOT, and detection of HIV-specific IgM
      and IgA antibodies, are under development and promise to be very useful in the
      early diagnosis of vertical HIV infection. However, we will be able to accurately
      establish the sensitivity or specificity of the individual tests only when we
      have results of large prospective studies. These studies should compare different
      diagnostic methods and correlate the results of tests performed sequentially in
      neonates and young infants with the natural history of their disease process and
      eventual clinical outcome.

PMID- 1987349
TI  - Childhood human immunodeficiency virus infection: the spectrum of costs.

PMID- 1987350
TI  - Comparison of HIV detection by virus isolation in lymphocyte cultures and
      molecular amplification of HIV DNA and RNA by PCR in offspring of seropositive
      mothers.
AB  - An early and accurate diagnosis of HIV infection is needed in the offspring of
      seropositive mothers. To this end, we have used two techniques for the direct
      detection of HIV in 12 newborns tested within 2 weeks after birth and 12
      children. HIV isolation was carried out in lymphocyte cocultures and compared
      with detection of DNA and RNA sequences by molecular amplification using the
      polymerase chain reaction (PCR). In lymphocyte cocultures, HIV was isolated in 8
      of 24 cases (33%), including 3 newborns, 3 symptomatic children, and 2
      asymptomatic ones. HIV DNA was detected by PCR in twice as many cases, i.e., in
      16/24 cases (66%), including 7/12 newborns, 4/4 symptomatic children, and 5/8
      asymptomatic ones, 2 of whom became seronegative, HIV RNA was detected in 10 of
      16 cases (60%) with detectable HIV DNA, including all of the cases who had a
      positive HIV isolation. Only children with clinical or biological signs of HIV
      infection were positive for HIV RNA. Furthermore, signs of HIV infection appeared
      within 6 months in three of the four newborns who were positive for HIV RNA at
      birth. These results indicate that HIV DNA detection by PCR is far more sensitive
      than HIV isolation in culture for the early diagnosis of HIV infection in
      offspring of seropositive mothers. HIV RNA detection appears to be a useful
      prognostic marker since it does correlate with disease progression and may serve
      as a clue for HIV replication in vivo.

PMID- 1987351
TI  - Polypharmacy among patients attending an AIDS clinic: utilization of prescribed,
      unorthodox, and investigational treatments.
AB  - The objective of this study was to describe the utilization and characteristics
      associated with the use of prescribed, over-the-counter, investigational, and
      unorthodox treatments among AIDS clinic patients. This report is derived from
      cross-sectional data obtained using structured telephone surveys. Study
      participants (n = 197) were recruited from the University of California, San
      Francisco, Medical Center AIDS clinic. One hundred eighty-nine participants (96%)
      received 1-24 prescription medications during the 3 months prior to interview.
      Those with an AIDS diagnosis received a relatively greater number of prescription
      drugs (p = 0.0001); an average of 5.6 prescribed medications were used by AIDS
      patients versus 4.8 among AIDS-related complex and 2.3 among asymptomatic
      patients. Thirty-one percent participated in drug trials during the 3 months
      before interview, including 18% who were in multiple studies. Twenty-nine percent
      used unorthodox treatments. Seventy-five (40%) received prescription medication
      from a provider other than their primary provider. A more advanced stage of
      illness was associated with the use of unorthodox treatments (p = 0.003): users
      of these treatments had a greater educational attainment than nonusers (p = 0.03)
      and were significantly less likely to report that their primary provider was
      aware of all the treatments they used (odds ratio = 2.1, p less than 0.03). We
      conclude that use of polypharmacy among some AIDS clinic patients is common,
      could create an increased risk for adverse drug reactions, and may affect
      clinical drug trials. Despite having decided to obtain care at a university-based
      clinic, many of the participants of this study also chose to receive unorthodox
      therapies and care from nonprimary medical providers.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1987352
TI  - Survival differences in patients with AIDS.
AB  - To define the clinical, demographic, and behavioral variables that may influence
      survival in patients with AIDS, we studied 526 patients with AIDS diagnosed
      through September 1987 who were cared for at a single medical center. A diversity
      of racial and ethnic backgrounds, ages, both men and women, and all risk
      behaviors except hemophilia were well represented. The initial AIDS defining
      diagnosis was the most powerful predictor of survival. The median survival was
      12.8 months for patients presenting with Kaposi's sarcoma (p less than 0.001),
      10.9 months for patients presenting with Pneumocystis carinii pneumonia (p less
      than 0.001), and 4.8 months for patients presenting with other infections or
      neoplasms (p less than 0.02). For the entire series, male sex and younger age
      were associated with more favorable survival (p less than 0.025). For those
      presenting with Pneumocystis carinii pneumonia, in addition to younger age (p
      less than 0.025), black race (p less than 0.025) and the combination of male sex
      and intravenous drug use (p less than 0.005) were associated with a more
      favorable survival. Within a setting of comparable clinical care, survival from
      the point of diagnosis of AIDS is associated most strongly with the initial AIDS
      diagnosis, but differences in age, gender, race, and risk behavior also exert an
      influence on survival.

PMID- 1987353
TI  - The NF kappa B independent cis-acting sequences in HIV-1 LTR responsive to T-cell
      activation.
AB  - The rate of transcription initiation directed by the long terminal repeat (LTR)
      of HIV-1 increases in response to mitogenic stimuli of T cells. Here we show that
      the response of the HIV-1 LTR may be governed by two independent sequences
      located 5' to the site of transcription initiation sequences that bind either
      NFAT-1 or NF kappa B. The rate of LTR-directed gene expression increased in
      response to treatment with either a phorbol ester or tumor necrosis factor alpha
      if either the NFAT-1 or NF kappa B binding sites were deleted, but failed to
      respond to these mitogenic stimuli if both sequences were absent. The HIV-1
      mutant virus containing both NF kappa B and NFAT-1 deletion was able to replicate
      although at a much decreased growth rate, while the deletion of NFAT-1 alone
      increased the viral growth rate in Jurkat cells. Neither deletion of NF kappa B
      nor deletion of NFAT-1 decreased activation of viral replication by phorbol
      ester.

PMID- 1987354
TI  - Plasma adenosine deaminase2: a marker for human immunodeficiency virus infection.
AB  - Plasma concentrations of the two isoenzymes of adenosine deaminase (ADA, E.C.
      3.5.4.4), adenosine deaminase1 (ADA1) and adenosine deaminase2 (ADA2), were
      measured in a cohort of ambulatory patients infected with the human
      immunodeficiency virus (HIV) and controls. A sensitive isoenzyme-specific
      radioisotopic assay system was developed for these studies. Among 22 HIV-infected
      patients, plasma ADA2 was significantly elevated as compared with 16 control
      subjects (p less than 0.01) and 6 uninfected subjects having a risk factor for
      HIV infection (p less than 0.01). Plasma ADA2 was not associated with the stage
      of disease as defined by clinical status (p greater than 0.05) or helper (CD4)
      lymphocyte count (p greater than 0.05). Available evidence suggests that elevated
      plasma ADA2 could be a useful surrogate marker for HIV infection that occurs
      early in the disease process.

PMID- 1987355
TI  - Detection of salivary HIV-1-specific IgG antibodies in high-risk populations in
      Zaire.
AB  - Saliva and blood samples were tested for human immunodeficiency virus-1 (HIV-1)
      antibodies in two high-risk populations in Kinshasa, Zaire. In a seroprevalence
      study of 458 sexually transmitted disease (STD) clinic attendees, 142 of 145
      seropositive individuals had enzyme-linked immunosorbent assay (ELISA)-positive
      saliva samples (97.9% sensitivity). All saliva samples from seronegative patients
      were ELISA-negative (100% specificity). Of the 142 ELISA-positive saliva
      specimens, 137 were also Western blot-positive (94.5% sensitivity). In a
      subsequent seroincidence study of 315 initially seronegative female prostitutes
      followed during 183 woman-years of observation, 9 of 14 women who seroconverted
      (7.7% seroincidence) had ELISA-positive saliva samples at the time seroconversion
      was detected. Only three of these saliva specimens could be confirmed by Western
      blot. Although salivary testing for HIV-1 antibodies using conventional assays
      was not sensitive in detecting recent seroconversions, screening of salivary
      samples for HIV-1 antibody provides a convenient alternative method for
      conducting seroprevalence surveys in populations in whom venipuncture is not
      possible or convenient.

PMID- 1987356
TI  - The costs of AIDS in Los Angeles.
AB  - This article reports on the findings of a study of medical and non-medical
      expenditures of persons with acquired immune deficiency syndrome (AIDS) in Los
      Angeles in 1987 and 1988. Sociodemographic and clinical data as well as
      information on medical and nonmedical expenditures on 36 persons with AIDS were
      obtained through patient interviews and review of medical bills. Persons with
      AIDS required a mean of 1.6 hospitalizations per year and 17 days of in-hospital
      care. Mean charges for the first 12 months after diagnosis of AIDS were $22,272
      for inpatient medical care and $22,850 for outpatient medical care. Overall,
      medical costs averaged $45,122 per patient per year with almost one-third of
      these costs devoted to outpatient pharmaceuticals, such as AZT and aerosolized
      pentamidine. Mean nonmedical costs of care for volunteer services, counselling,
      and in-kind assistance were $9,276. These results were similar to recently
      published estimates of medical costs of persons with AIDS. However, our data
      support changing problems of care for PWAs with increased use of outpatient
      medical care and pharmaceuticals and decreased use of in-hospital resources.

PMID- 1987358
TI  - Increased plasma prostacyclin in AIDS.

PMID- 1987357
TI  - Presence of SIV antibodies in the sera of infants born to SIV-seronegative
      monkeys.

PMID- 1987359
TI  - Carcinogenic potency correlations: real or artifactual?
AB  - It has been suggested by various investigators that observed interspecies
      correlations of carcinogenic potency estimates based on bioassays are to a degree
      due to tautologous aspects of experimental designs. Some authors have even
      suggested that carcinogenic potency estimates derived from chronic bioassays are
      little more than experimental design artifacts. In this paper it is argued that
      constraints imposed by the use of the one-hit model to estimate carcinogenic
      potency are more restrictive than potential experimental design constraints.

PMID- 1987360
TI  - Pesticides and the Third World.
AB  - Many developing countries are importing industrial processes that make use of
      toxic chemicals. By the same token, pesticides, which are toxic by design, are
      also used increasingly in agriculture and in public health programs to control
      pests and vector-borne diseases. Recent estimates suggest that pesticides account
      for more than 20,000 fatalities yearly, and that most of these will have occurred
      in developing countries. This may actually be a gross underreporting. Although
      organophosphate and carbamate insecticides are still responsible for many of
      those poisoning cases, herbicides such as paraquat are also increasingly being
      implicated in fatal poisoning cases. Newer pesticides such as the synthetic
      derivatives of pyrethrin, which were believed to be relatively safe to humans,
      now appear to be implicated in some serious cases of intoxication. Community
      based pest control using locally available botanical pesticides could have severe
      consequences unless the toxicity of these compounds is carefully assessed
      relative to nontarget organisms. A high proportion of pesticide intoxications
      appear to be due to lack of knowledge, unsafe attitudes, and dangerous practices.
      The technology available to small farmers for pesticide application is often
      inappropriate: faulty sprayers, lack of protective equipment adapted to tropical
      conditions, nonexistent first-aid provisions. Agricultural extension is often not
      oriented to the transfer of information relative to the dangers inherent in the
      use of pesticides. The lack of information at all levels may be one of the most
      important causative factors of chemical intoxication in developing countries.
      Research should at this time concentrate on behaviors leading to chemical
      intoxication. This should be done concurrently with proper prospective and
      retrospective surveys of poisonings in developing country communities. More
      information should be sought relative to the decision processes of import,
      legislation, and licensing. Research and development efforts in appropriate
      technology and safety devices are also critically needed.

PMID- 1987362
TI  - Cadmium-induced changes in luminal fluid pH in testis and epididymis of the rat
      in vivo.
AB  - The effects of a single low subcutaneous dose of cadmium chloride (CdCl2) (2.7
      mg/kg body weight) on in situ pH in the rat testis and epididymis, plasma
      testosterone, and testis and epididymis weights were investigated in this study.
      Values for in situ pH in seminiferous tubules (6.97 +/- 0.01), proximal caput
      (6.62 +/- 0.01), middle caput (6.59 +/- 0.01), and proximal cauda epididymidis
      (6.84 +/- 0.01) of sham-treated rats were significantly more acid than systemic
      arterial blood pH (7.41 +/- 0.01). Cadmium (Cd) administration was associated
      with significant alkalinization of luminal fluid in seminiferous tubules (7.17 +/
      0.02) and in proximal (7.02 +/- 0.04) and middle caput (6.99 +/- 0.03), but not
      in proximal cauda epididymidis (6.88 +/- 0.02), after 1 d. Eleven days after Cd
      administration, marked alkalinization of luminal fluid was observed in all
      segments studied including proximal cauda epididymidis (7.21 +/- 0.02). Plasma
      testosterone concentration in sham-treated rats was 1.93 +/- 0.30 ng/ml and was
      reduced significantly after 1 d (0.56 +/- 0.06 ng/ml) and persisted after 11 d
      postexposure (0.57 +/- 0.07 ng/ml). Testis and epididymis weights were not
      altered 1 d after Cd exposure but were significantly reduced after 11 d. These
      studies suggest that the alkalization observed in luminal fluid of seminiferous
      tubules and epididymal duct of the rat after subcutaneous CdCl2 administration
      may be the result of structural degeneration of the testis associated with
      inhibition of Leydig-cell androgen production.

PMID- 1987361
TI  - Inhibition of metabolic coupling by metals.
AB  - Several metals were evaluated in cell cultures for their ability to inhibit
      metabolic coupling, the intercellular transfer of low-molecular-weight
      metabolites by directly connecting gap junctions. To monitor inhibition of
      metabolic coupling, wild-type Chinese hamster V79 cells proficient in metabolism
      of 6-thioguanine (6-TG) were cocultured with mutant V79 cells unable to
      metabolize 6-TG to its toxic metabolite (6-TG-resistant cells). In the presence
      of 6-TG, inhibition of metabolic coupling by the metals was manifested as
      increased recovery of 6-TG-resistant cells compared to recovery in untreated
      cocultures. The toxic metal compounds, arsenic(V) acid, mercury(II) chloride,
      lead(II) acetate, and nickel(II) chloride, significantly (p less than .05)
      increased recovery of 6-TG-resistant cells at concentrations that did not alter
      cell survival. However, because the increased recovery observed with nickel
      showed no concentration dependence, its importance may be negligible. Cadmium
      chloride increased 6-TG-resistant cell recovery only at a toxic concentration,
      and zinc sulfate failed to increase recovery. These data demonstrate that some
      metal compounds inhibit metabolic coupling, and suggest that inhibition of
      junctional communication should be further evaluated as a potential mechanism of
      toxicity of some metals.

PMID- 1987363
TI  - Effects of 2,4,5-trichlorophenoxyacetic acid, pentachlorophenol,
      methylprednisolone, and Freund's adjuvant on 2-hydroxyethylnitrosourea
      carcinogenesis in MRC-Wistar rats.
AB  - A link was proposed between human non-Hodgkin's lymphoma and exposure to 2,4,5
      trichlorophenoxyacetic acid (245T) and pentachlorophenol (PCP). To test this view
      and the hypothesis that immune suppression or stimulation could affect B-cell
      lymphoma (BCL) induction, we administered chronically to MRC-Wistar (MRC-W) rats
      of both sexes 98% pure 245T (600 mg/kg diet), 86% pure PCP (500 mg/kg diet),
      methylprednisolone (20 mg/kg ip weekly), and Freund's adjuvant (0.5 ml im every 3
      6 wk) for 40 wk, together with 75 mg 2-hydroxyethylnitrosourea (HENU)/l drinking
      water, a system known to induce B-cell lymphoma. The 245T was shown to contain
      only 1-4 micrograms/kg each of 2,3,7,8-tetrachlorodibenzodioxin (TCDD) and
      2,3,7,8-tetrachlorodibenzofuran (TCDF), but the PCP contained 25 micrograms TCDD
      and 670 micrograms TCDF/kg. HENU given alone induced B-cell lymphoma and
      osteosarcoma as before, with higher incidences of both tumors in males than in
      females. The B-cell lymphoma diagnosis was confirmed by immunologic typing of
      cell-surface markers and by probes for gene rearrangements. Coadministration with
      HENU of three of the four test agents did not affect tumor incidence, but PCP
      acted synergistically with HENU to induce acute myelocytic leukemia. PCP given
      alone or with HENU induced a 40-67% incidence of liver cell adenomas in the
      female rats. These effects were probably not due to TCDD in the PCP. HENU induced
      acute myelocytic leukemia and lung tumors in Wistar rats and n-butylnitrosourea
      induced acute myelocytic leukemia in MRC-Wistar rats, indicating that B-cell
      lymphoma induction was specific to the HENU-MRC-Wistar rat model.

PMID- 1987364
TI  - Effect of systemic exposure to parathion on the dark adapted pupil dilation of
      cynomolgus monkeys.
AB  - The constriction of pupil dilation following dark adaptation was studied as a
      potentially useful biological monitor of systemic exposure to organophosphorus
      pesticides (OPs). Pupil dilation and blood cholinesterase levels were monitored
      in 4 cynomolgus monkeys following oral administration of 2.0 mg/kg parathion in
      corn oil. No consistent pattern of change in pupil/iris diameter ratios following
      exposure was found despite depressions in blood cholinesterase activities of 27
      50% for red cells and 65-80% for plasma. A slight mydriasis was observed in one
      of the monkeys, who appeared the most affected behaviorally by the exposure.
      Results of this work suggest that the measurement of pupil dilation after dark
      adaptation is not a sensitive indicator for systemic exposure to OPs. However, in
      situations where direct exposure to the eyes may occur, such as during aerial or
      airblast pesticide applications, other studies indicate that constriction of
      pupil dilation can occur at exposure levels below those resulting in systemic
      effects.

PMID- 1987365
TI  - Comparison of toxicity induced by iodine and iodide in male and female rats.
AB  - In risk assessments the various forms of iodine have been treated as if they were
      toxicologically equivalent. While iodide (I-) and iodate (IO3-) have been
      studied, no studies concerned with the subchronic toxicity of iodine (I2) have
      been conducted in experimental animals. This study examined toxicities associated
      with iodine. Rats were treated with 0, 1, 3, 10, and 100 mg/l of either iodine or
      iodide (as Nal) in the drinking water for 100 d. Treatment had no effect on body,
      brain, or heart weights in either sex, or on testes weights in male rats.
      Although differences in kidney and liver weights were noted, they did not appear
      to be treatment related. Thyroid weight in male rats was significantly increased
      with an increasing concentration of iodide in the water, but not iodine. In
      contrast, thyroid weight decreased at the highest dose of iodide in female rats.
      Hematocrit, hemoglobin, and blood urea nitrogen (BUN) values were relatively
      constant and did not vary with treatment. There were no significant differences
      in AST, ALT, cholesterol, and triglyceride values. After 10 d on treatment a dose
      related trend in increased plasma T4 concentrations was observed in both sexes
      treated with iodine. Statistically significant increases in the T4/T3 ratio in
      both sexes was also noted with iodine treatment. This increase was maintained for
      100 d of treatment. Iodide did not produce this effect at 10 d. Although there
      was a significant increase in T4/T3 ratios in female rats after 100 d of
      treatment with iodide, the magnitude of the changes was smaller than that
      observed with iodine treatments. The results of this study indicate that iodine
      and iodide affect thyroid hormone status in substantially different ways.

PMID- 1987367
TI  - The long terminal repeat is not a major determinant of the cellular tropism of
      human immunodeficiency virus type 1.
AB  - The long terminal repeats (LTRs) of human immunodeficiency virus type 1 (HIV-1)
      strains from the central nervous systems of four patients with AIDS and of an HIV
      1 isolate which is highly macrophage-tropic were isolated by using the polymerase
      chain reaction. In transient transfection assays, these LTRs demonstrated no
      significant difference in basal or stimulated levels of transcription in any of a
      variety of cell lines tested, compared with expression directed from the LTR of a
      T-lymphocyte-tropic strain of HIV-1. Chimeric viruses were created with the LTRs
      of the macrophage-tropic and brain-derived viruses ligated to the viral backbone
      from a T-lymphocyte-tropic strain. No change in cellular tropism was demonstrated
      with these chimeric viruses. Thus, unlike the LTRs of some murine retroviruses,
      the LTR of HIV-1 does not appear to play a major role in determining cellular
      tropism.

PMID- 1987366
TI  - Restricted virus replication in the spinal cords of nude mice infected with a
      Theiler's virus variant.
AB  - The Daniels strain of Theiler's murine encephalomyelitis produces a chronic
      disease which is an animal model for human demyelinating disorders. Previously,
      we selected a neutralization-resistant virus variant producing an altered and
      diminished central nervous system disease in immunocompetent mice which was
      evident during the later stage of infection (after 4 weeks) (A. Zurbriggen and R.
      S. Fujinami, J. Virol. 63:1505-1513, 1989). The exact epitope determining
      neurovirulence was precisely mapped to a capsid protein, VP-1, and represents a
      neutralizing region (A. Zurbriggen, J. M. Hogle, and R. S. Fujinami, J. Exp. Med.
      170:2037-2049, 1989). Here, we present experiments with immunoincompetent animals
      to determine viral replication, spread, and targeting to the central nervous
      system in the absence of detectable antibodies or functional T cells. Nude mice
      were infected orally, and the virus was monitored by plaque assay,
      immunohistochemistry, and in situ hybridization. Early during the infection (1
      week), the variant virus induced an acute disease comparable to that induced by
      the wild-type virus in these nude mice. Alterations in tropism in the central
      nervous system were not apparent when wild-type parental Daniels strain virus was
      compared with the variant virus. Moreover, variant virus replicated in tissue
      culture (BHK-21 cells) to similarly high titers in a time course identical to
      that of the wild-type virus (A. Zurbriggen and R. S. Fujinami, J. Virol. 63:1505
      1513, 1989). However, replication of the variant virus versus the wild-type virus
      within the spinal cord of athymic nude mice infected per os was substantially
      restricted by 6 weeks postinfection. Therefore, the reduced neurovirulence in the
      later stage (6 weeks) of the disease is most likely due to a diminished growth
      rate or spread of the variant virus in the central nervous system rather than to
      marked differences in viral tropism.

PMID- 1987368
TI  - Expression and characterization of the thymidine kinase gene of African swine
      fever virus.
AB  - The thymidine kinase (TK) gene of African swine fever virus (ASFV) was located
      within the viral genome by using two degenerate oligonucleotide probes derived
      from sequences of the vaccinia virus and cellular TK genes. The TK gene was
      mapped within a 0.72-kbp BglII-XhoI fragment (0.242 to 0.246 map units) derived
      from a 23.9-kbp SalI-B fragment of the ASFV genome. Identification of this region
      as the ASFV TK gene was confirmed by expression of TK in Escherichia coli and by
      the synthesis of active TK in a cell-free system programmed with RNA synthesized
      in vitro. The sequenced gene for TK includes an open reading frame of 588
      nucleotides encoding a protein of 196 amino acids. The deduced amino acid
      sequence shows 32.4% identity with the TK of vaccinia virus.

PMID- 1987369
TI  - Different biological activities of the hetero- and homodimers formed by the 47-
      and 43-kilodalton proteins of transcription factor ATF/E4TF3.
AB  - The transcription factor ATF/E4TF3 stimulates transcription from the adenovirus
      early region 4 (E4) promoter by binding to specific promoter elements. Among the
      multiple forms of ATF/E4TF3, two forms with molecular masses of 47 and 43 kDa,
      which are most active in transcription in vitro from the E4 promoter, have been
      purified to homogeneity from HeLa cells by sequence-specific DNA affinity
      chromatography and biochemically characterized. Each purified protein formed a
      homodimer. These two homodimers were easily altered into a heterodimer when mixed
      together in the absence, but not in the presence, of the specific DNA sequence.
      All of these dimers were able to activate transcription in vitro from the E4
      promoter by binding to the specific DNA sequence. Their activities to bind to DNA
      or stimulate transcription were different. The ability of the 47-kDa homodimer to
      stimulate transcription in vitro from the E4 promoter was approximately nine and
      three times higher than the abilities of the 43 kDa homodimer and the
      heterodimer, respectively, at the same level of DNA-binding activity. However,
      the affinity of the 47-kDa homodimer for DNA was lower than that of the 43-kDa
      homodimer, and the heterodimer had intermediate affinity. These results are the
      first to show differential binding and transcriptional activation activities of
      the different dimers of ATF/E4TF3, using purified cellular proteins rather than
      cloned gene products.

PMID- 1987370
TI  - Hepatitis B virus core antigen has two nuclear localization sequences in the
      arginine-rich carboxyl terminus.
AB  - Expression of the hepatitis B virus core antigen (HBcAg) in mouse NIH 3T3
      fibroblasts has been shown previously (A. McLachlan et al., J. Virol. 61:683-692,
      1987) to result in the nuclear localization of this polypeptide. Since the
      carboxyl terminus of HBcAg contains four clusters of arginine residues which
      resemble nuclear localization sequences identified in other nuclear proteins, a
      series of carboxyl-terminus-truncated HBcAg polypeptides were expressed in mouse
      fibroblasts to examine the role of these sequences in the cellular localization
      of HBcAg. By immunofluorescence and cell fractionation analysis, it was
      demonstrated that regions of the HBcAg polypeptide including the most carboxyl
      terminal (cluster 1) and amino-terminal (cluster 4) clusters of arginine residues
      represent distinct and independent nuclear localization sequences for this
      polypeptide. Substitution of a threonine residue for the second arginine residue
      in cluster 4 inactivates the nuclear localization signal in this region of the
      HBcAg polypeptide, demonstrating the importance of this residue to this signal
      sequence. However, HBcAg fails to accumulate in the nucleus only when both
      nuclear localization signal sequences are simultaneously deleted or disrupted by
      mutation. The possible significance of the nuclear localization sequences
      identified in the HBcAg polypeptide is discussed in the context of the role of
      the nucleocapsid in the hepatitis B virus life cycle.

PMID- 1987371
TI  - Genetic characterization of human immunodeficiency virus type 1 nef gene products
      translated in vitro and expressed in mammalian cells.
AB  - Expression of the human immunodeficiency virus type 1 nef gene was studied by in
      vitro transcription-translation and by transfection into monkey COS cells. Two
      Nef-related peptides, of 27 and 25 kDa, were identified by immunoprecipitation
      with anti-Nef antibodies. The relation between these two proteins was determined
      by metabolically labeling transfected COS cells and by deleting the initiator
      methionine of nef. We found that the 25-kDa polypeptide is not a cleavage product
      of 27-kDa Nef but rather is initiated from an internal ATG 57 bases downstream
      from the Nef initiation site. Myristoylation of the 27-kDa but not of the 25-kDa
      Nef was demonstrated by the contranslational modification of Nef in an in vitro
      reticulocyte translation system. The myristoylation pattern of the two Nef
      polypeptides further implies that the 25-kDa polypeptide lacks the amino terminus
      of 27-kDa Nef. Cellular localization of the various forms of Nef was studied in
      transiently transfected COS cells. Myristoylation was found to be necessary for
      membrane association of Nef. Myristoylation-deficient 27-kDa Nef mutant and 25
      kDa Nef were confined to the soluble cytoplasmic fraction of transfected cells,
      whereas part of the wild-type 27-kDa Nef was membrane attached.

PMID- 1987373
TI  - Temporal synthesis of proteins and RNAs during human astrovirus infection of
      cultured cells.
AB  - Astroviruses are nonenveloped particles with a distinctive star-shaped surface
      structure that have been detected by electron microscopy in stool samples from
      humans and animals with gastroenteritis. We examined the patterns of
      macromolecular synthesis in astrovirus-infected cells with a goal of establishing
      a molecular basis for taxonomic classification. Trypsin is required for
      continuous replication of astrovirus in cultured cells; however, during a single
      cycle of infection, astrovirus antigen was synthesized earlier and at higher
      levels when serum, rather than trypsin, was included in the growth medium. This
      enhanced production of antigen, as measured by enzyme immunoassay, was
      accompanied by the appearance of aggregates of virus particles in the cytoplasm
      of infected cells. During astrovirus replication in cells cultured in the
      presence of serum, we detected a single infection-specific protein (90 kDa)
      beginning at 12 h postinfection. This protein was recognized by antiastrovirus
      rabbit serum and was sensitive to trypsin digestion in vitro, with the
      concomitant appearance of three smaller immunoreactive proteins (31, 29, and 20
      kDa). We also detected two dactinomycin-resistant RNAs (7.2 and 2.8 kb), both of
      which were polyadenylated, in the cytoplasm of astrovirus-infected cells. The
      larger of these two RNAs is presumably the viral genome, whereas the smaller
      species may be a subgenomic messenger. Comparison of the proteins and RNAs
      synthesized in astrovirus-infected cells with those of the recognized families of
      nonenveloped single-stranded RNA animal viruses suggests that astroviruses should
      not be classified as members of either Caliciviridae or Picornaviridae.

PMID- 1987372
TI  - Structural proteins of hog cholera virus expressed by vaccinia virus: further
      characterization and induction of protective immunity.
AB  - A cDNA fragment covering the genomic region that encodes the structural proteins
      of hog cholera virus (HCV) was inserted into the tk gene of vaccinia virus.
      Expression studies with vaccinia virus/HCV recombinants led to identification of
      HCV-specific proteins. The putative HCV core protein p23 was demonstrated for the
      first time by using an antiserum against a bacterial fusion protein. The
      glycoproteins expressed by vaccinia virus/HCV recombinant migrated on sodium
      dodecyl sulfate-gels identically to glycoproteins precipitated from HCV-infected
      cells. A disulfide-linked heterodimer between gp55 and gp33 previously detected
      in HCV-infected cells was also demonstrated after infection with the recombinant
      virus. The vaccinia virus system allowed us to identify, in addition to the
      heterodimer, a disulfide-linked homodimer of HCV gp55. The vaccinia virus/HCV
      recombinant that expressed all four structural proteins induced virus
      neutralizing antibodies in mice and swine. After immunization of pigs with this
      recombinant virus, full protection against a lethal challenge with HCV was
      achieved. A construct that lacked most of the HCV gp55 gene failed to induce
      neutralizing antibodies but induced protective immunity.

PMID- 1987374
TI  - Effectiveness of enteric immunization in the development of secretory
      immunoglobulin A response and the outcome of infection with respiratory syncytial
      virus.
AB  - Cotton rats were immunized via intranasal, intradermal, or enteric routes with
      respiratory syncytial virus (RSV) or a live recombinant vaccinia virus expressing
      the RSV F glycoprotein (vaccinia F). The animals were tested for the appearance
      of RSV-specific antibody responses in the serum, bronchoalveolar lavage, and
      nasal wash after immunization and for virus replication 4 days after intranasal
      challenge with RSV. RSV antibody response in the serum and respiratory tract was
      demonstrated in all immunization groups and was significantly increased after
      intranasal challenge with RSV. Immunoglobulin A (IgA) antibody response in
      bronchoalveolar lavage fluid after intranasal or enteric immunization was two- to
      threefold higher than that after intradermal immunization. Nasal-wash IgA
      antibody response was not significantly different among three immunization
      groups, although mean antibody titer was the highest in intranasal immunization
      group. Complete resistance to replication of RSV challenge was observed in the
      lungs of cotton rats immunized by the intranasal or enteric routes, whereas a low
      level of replication was detected in the lungs of rats immunized intradermally.
      Enteric or intradermal immunization conferred partial protection to the upper
      respiratory tract, but complete protection of the upper respiratory tract was
      observed in the intranasal immunization group. These observations suggest that
      while enteric immunization is quite effective in inducing antibody responses in
      the respiratory tract, the magnitude of antiviral immunity induced in the
      respiratory tract after intranasal immunization may be superior to that observed
      after enteric immunization.

PMID- 1987375
TI  - Identification of the very early transcribed baculovirus gene PE-38.
AB  - We have started to identify early viral RNAs that are transcribed at 1 h after
      inoculation to investigate the mechanism involved in the regulation of early gene
      expression of Autographa californica nuclear polyhedrosis virus (AcNPV). Cloned
      viral DNA fragments were hybridized to Northern (RNA) blots of polyadenylated RNA
      isolated from Spodoptera frugiperda cells at 1, 2, and 6 h postinfection to
      localize very early transcripts. Subsequently we prepared a cDNA library of
      polyadenylated RNA transcribed at 1 h after inoculation to analyze the cDNA
      clones corresponding to the major early RNAs. We identified a gene located
      upstream of the immediate-early gene IE-N extending in the opposite direction.
      Because of the very early expression during AcNPV infection and the transient
      expression in uninfected cells, we conclude that we found an immediate-early
      gene, designated PE-38. The determination of the nucleotide sequence of PE-38
      revealed one open reading frame potentially encoding a gene product of 38 kDa.
      Results of in vitro translation experiments suggest that a PE-38-specific
      polypeptide of approximately 38 kDa can be expressed. We have evidence from
      computer analyses that the predicted amino acid sequence includes two putative
      DNA-binding motifs, a zinc finger, and a leucine zipper.

PMID- 1987376
TI  - Complementation between avirulent Newcastle disease virus and a fusion protein
      gene expressed from a retrovirus vector: requirements for membrane fusion.
AB  - The cDNA derived from the fusion gene of the virulent AV strain of Newcastle
      disease virus (NDV) was expressed in chicken embryo cells by using a retrovirus
      vector. The fusion protein expressed in this system was transported to the cell
      surface and was efficiently cleaved into the disulfide-linked F1-F2 form found in
      infectious virions. The cells expressing the fusion gene grew normally and could
      be passaged many times. Monolayers of these cells would plaque, in the absence of
      trypsin, avirulent NDV strains (strains which encode a fusion protein which is
      not cleaved in tissue culture). Fusion protein-expressing cells would not fuse if
      mixed with uninfected cells or uninfected cells expressing the hemagglutinin
      neuraminidase (HN) protein. However, the fusion protein-expressing cells, if
      infected with avirulent strains of NDV, would fuse with uninfected cells,
      suggesting that fusion requires both the fusion protein and another viral protein
      expressed in the same cell. Fusion was also seen after transfection of the HN
      protein gene into fusion protein-expressing cells. Thus, the expressed fusion
      protein gene is capable of complementing the virus infection, providing an active
      cleaved fusion protein required for the spread of infection. However, the fusion
      protein does not mediate cell fusion unless the cell also expresses the HN
      protein. Fusion protein-expressing cells would not plaque influenza virus in the
      absence of trypsin, nor would influenza virus-infected fusion protein-expressing
      cells fuse with uninfected cells. Thus, the influenza virus HA protein will not
      substitute for the NDV HN protein in cell-to-cell fusion.

PMID- 1987377
TI  - Specific cessation of minus-strand RNA accumulation at an early stage of tobacco
      mosaic virus infection.
AB  - The time course of accumulation of viral plus-strand RNAs (genomic RNA and
      subgenomic mRNA for the coat protein) and minus-strand RNA in tobacco protoplasts
      synchronously infected with tobacco mosaic virus (TMV) RNA was examined. In
      protoplasts infected with the wild-type TMV L RNA, the plus and minus strands
      accumulated differently not only in quantity but also in the outline of kinetics.
      The time courses of accumulation of the genomic RNA and coat protein mRNA were
      similar: they became detectable at 2 or 4 h postinoculation (p.i.), and their
      accumulation increased until 14 to 18 h p.i. The accumulation rate reached the
      maximum at about 4 h p.i. and then gradually decreased. In contrast, accumulation
      of the minus-strand RNA ceased at 6 to 8 h p.i., at which time the plus-strand
      accumulation was already about 100 times greater and still continued vigorously.
      This specific halt of minus-strand accumulation was not caused exclusively by
      encapsidation of the genomic RNA, because a similar halt was observed upon
      infection with a deletion mutant that lacks the 30K and coat protein genes. Upon
      infection with a mutant that could not produce the 130K protein (one of the two
      proteins that are thought to be involved in viral RNA replication), the
      accumulation levels of both plus and minus strands were lower than that of the
      parental wild-type virus. Given these observations, possible mechanisms of TMV
      replication are discussed.

PMID- 1987378
TI  - Japanese encephalitis virus neurotropism is dependent on the degree of neuronal
      maturity.
AB  - In a study on Fischer rats, all animals infected with Japanese encephalitis virus
      (JEV) before the age of 13 days died, but animals infected after the age of 14
      days did not die, confirming the age-dependent resistance to JEV infection in the
      rat brain. A study of the kinetics of JEV infection in the developing rat brain
      disclosed that JEV antigen disappeared in a particular pattern, i.e., from the
      deeper layers to the upper layers of the motor cortex, which paralleled neuronal
      maturation in the cortex. Fifteen-day-old rats, which were resistant to JEV
      infection, received intracerebral transplants of neurons taken from 19-day
      embryos. When these animals were infected with JEV after transplantation, viral
      antigen was detected only in the embryonal neurons soon after transplantation.
      Thus, it can be concluded that the susceptibility to JEV infection in the rat
      brain is closely associated with neuronal immaturity.

PMID- 1987380
TI  - Transient expression of the Autographa californica nuclear polyhedrosis virus
      immediate-early gene, IE-N, is regulated by three viral elements.
AB  - Autographa californica nuclear polyhedrosis virus (AcMNPV) is a double-stranded
      DNA virus that expresses several immediate-early genes under the control of
      different promoters. The expression of one of these transcription units, IE-N, is
      shown here, by a transient expression assay, to be regulated by both cis- and
      trans-acting viral elements. The steady-state levels of IE-N mRNA were very
      abundant soon after infection but were nearly undetectable during the late phase
      of the viral life cycle. Analysis of the transient expression of a reporter
      construct driven by the IE-N promoter (IE-NCAT) was conducted to define viral
      elements which regulate IE-N gene expression. Viral enhancer hr1 and two
      immediate-early genes, IE-1 and IE-N, were shown to affect relative levels of
      reporter enzyme activity produced by IE-NCAT. The hr1 enhancer stimulated the
      expression of IE-NCAT, independent of orientation and position relative to the
      promoter and in the absence of any trans-acting viral factors. Regulation of IE
      NCAT expression by the IE-1 and IE-N genes required less than 290 bp of promoter
      sequences upstream of the site of transcription initiation and was not dependent
      upon the hr1 enhancer. Coexpression of the IE-N gene had an autostimulatory
      effect upon IE-NCAT activity, whereas coexpression of the IE-1 gene reduced
      levels of reporter activity. The levels of reporter activity measured upon
      coexpression of either immediate-early gene with IE-NCAT linked to the hr1
      enhancer appear to be the combined result of both cis- and trans-regulatory
      elements influencing expression from IE-NCAT. These results suggest that IE-N
      gene expression in baculovirus infection may be influenced by the concerted
      activity of three AcMNPV regulatory elements.

PMID- 1987379
TI  - Mutagenesis of protease cleavage sites in the human immunodeficiency virus type 1
      gag polyprotein.
AB  - The virally encoded protease of human immunodeficiency virus (HIV) is responsible
      for specific cleavage events leading to the liberation of the enzymes reverse
      transcriptase, integrase, ribonuclease H, and the core proteins from the gag-pol
      and gag polyprotein precursors. Utilizing gag polyprotein synthesized in vitro,
      we have shown that this substrate is sequentially cleaved by purified HIV
      protease to yield products that on the basis of their sizes and
      immunoreactivities correspond to p15, p6, p7, p17, and finally mature p24. We
      have placed unique restriction sites flanking the p17-p24 domain in order to
      facilitate replacement of cleavage site sequences by utilizing oligonucleotide
      cassettes. Replacement of the rapidly cleaved methionine-methionine bond at the
      p24-p15 junction with tyrosine-proline or replacement of the tyrosine-proline
      bond at the p17-p24 junction with methionine-methionine results in sites that
      cannot be efficiently cleaved. A basic amino acid at the p17-p24 scissile bond is
      not tolerated. Replacement of this cleavage site with an inverted repeat amino
      acid sequence gives intermediate rates of cleavage. In an attempt to convert the
      p17-p24 domain into a p24-p15 domain, residues flanking the scissile bond were
      exchanged in an expanding iterative fashion. When four residues flanking the
      scissile bond had been replaced, the rate of cleavage relative to that of the
      native p17-p24 sequence was increased fourfold. The cleavage rate of the native
      p24-p15 sequence is still some 10-fold greater than that of the p17-p24 sequence,
      suggesting that more-distant residues significantly affect the cleavage rate.

PMID- 1987381
TI  - Extracorporeal renal artery reconstruction for renovascular hypertension.
AB  - Extracorporeal reconstruction can be applied to the successful repair of stenoses
      in the distal renal artery and its hilar branches. This study evaluates the short
      and long-term results of extracorporeal renal artery reconstruction in 65
      patients, including 5 children, with renovascular hypertension who were treated
      from 1974 through 1989. The mean age of the patients was 37 years (range, 7 to 67
      years). The cause of the stenoses was arteriosclerosis in 8 patients,
      fibrodysplasia in 54 patients, and miscellaneous in 3. Hypertension was severe
      before treatment with a mean blood pressure of 187/147 mm Hg that was reduced to
      a mean of 159/102 mm Hg after medical therapy. Ten patients had renal
      dysfunction. Results were evaluated both at short-term intervals (mean, 7.9
      months; 64 patients) and long-term intervals (mean, 5.9 years; 60 patients),
      after surgery. Blood pressure responses were classified as beneficial
      (cured/improved) or failures. Anatomic results were evaluated by angiography in
      98% of the patients at the short-term interval and in 77% of the patients at the
      long-term interval. Extracorporeal renal artery surgery was performed on 78
      kidneys among 65 patients (unilateral, 45 patients; bilateral, 13 patients;
      unilateral extracorporeal and contralateral in situ, 7 patients). In most of the
      cases autologous arterial graft was used for reconstruction. Early in the series
      one patient died as a result of the operative procedure (1/65, 1.5%). A
      beneficial blood pressure response occurred in 53 patients (53/65; 82%) at the
      short-term interval and in 49 patients (49/61; 80%) at the long-term interval,
      with the average blood pressure at the short-term interval being 138/85 mm Hg and
      at the long-term interval being 139/85 mm Hg. Renal function improved in all
      patients with preoperative renal dysfunction. Graft stenosis or occlusion of the
      main renal artery was neither observed at the short-term interval nor at the long
      term interval. However, residual stenoses were observed in 9 of the 163
      reconstructed distal branches (5.5%). Extracorporeal renal artery reconstruction
      with autologous arterial grafts can be effectively applied to lesions of the
      distal main renal artery and its hilar branches with durable functional results.

PMID- 1987382
TI  - The clinical course of residual carotid arterial disease.
AB  - Over a 5-year period 642 patients underwent 686 carotid endarterectomies with
      patch closure and intraoperative surveillance with continuous-wave Doppler. The
      perioperative stroke rate was 1.5%. Patients were screened with duplex scans
      immediately after operation for the presence of residual carotid lesions, and
      followed every 3 to 6 months for either the development of a true recurrent
      lesion or a change in a residual one. Five hundred thirty-nine arteries (84%) had
      no postoperative abnormalities. The incidence of recurrent carotid lesions in
      this groups was 1.5%, 3.4%, and 5.2% at 1, 2, and 3 years, respectively. The
      incidence of symptoms in this group was 0.2%, 0.7%, and 1.4% at 1, 2, and 3
      years, respectively. The earliest recurrence or symptom occurred 8 months from
      operation. One hundred forty-seven arteries had residual lesions that were more
      common when either a temporary shunt was used or the operation was carried out
      above the hypoglossal nerve or below the omohyoid muscle. Sixty-one patients who
      had plaque proximal to the arteriotomy without a significant stenosis were
      followed an average of 21 months. There were no changes in plaque morphology and
      no proven symptoms related to the residual lesion. Fifty-six patients with both
      plaque and significant hemodynamic abnormalities in the carotid bulb were
      followed an average of 18 months. Seven of these patients (12.5%) had either a
      significant deterioration of the lesion or a symptom from it. Each event occurred
      within 6 months of operation. Thirty patients had significant flow abnormalities
      but no visible plaque. None of these lesions deteriorated. Although common,
      residual carotid lesions are benign unless the lesion is characterized by both
      plaque within the artery and a hemodynamically significant stenosis. These
      lesions should be further investigated and treated when discovered.

PMID- 1987383
TI  - Long-term follow-up of patients operated on for recurrent carotid stenosis.
AB  - We reviewed our experience with 29 operations for recurrent carotid stenosis in
      27 patients who underwent both their primary carotid endarterectomy and their
      reoperations at our institution. These 27 patients represent 4% of the 667
      patients who underwent primary carotid endarterectomies at our institution and
      who are included in our carotid follow-up registry. Reoperation was prompted by
      recurrent symptoms in 19/29 (65.5%) cases. Comparison of long-term stroke
      prevention in those patients who did (84% at 5 years, 78.6% at 10 years) and did
      not (90.3% at 5 years, 83.6% at 10 years) develop recurrent stenosis requiring
      reoperation revealed no statistically significant difference (p = 0.48) when
      measured from the time of primary operation. The perioperative stroke and death
      rates for reoperation (3.4% and 0%) were acceptable. We conclude that with our
      acceptably low perioperative stroke morbidity (3.4%), surgery for recurrent
      carotid stenosis in symptomatic patients or in asymptomatic patients with high
      grade (greater than or equal to 75%) stenosis maintains the durable stroke
      prevention offered by primary carotid endarterectomy.

PMID- 1987384
TI  - The association of elevated plasma homocyst(e)ine with progression of symptomatic
      peripheral arterial disease.
AB  - Plasma homocyst(e)ine (the sum of free and bound homocysteine, homocystine, and
      the mixed disulfide homocysteine-cysteine, expressed as homocysteine) levels were
      determined by high performance liquid chromatography in 214 patients with
      symptomatic (claudication, rest pain, gangrene, amputation) lower extremity
      arterial occlusive disease and/or symptomatic (stroke, cerebral transient
      ischemic attacks) cerebral vascular disease and in 103 control persons. Mean
      plasma homocyst(e)ine was significantly higher in patients than in controls
      (14.37 +/- 6.89 nmol/ml vs 10.10 +/- 2.16, p less than 0.05). Thirty-nine percent
      of patients (83 of 214) had plasma homocyst(e)ine values greater than control
      mean + 2 standard deviations. Plasma homocyst(e)ine values were contrasted to
      age, male sex, diabetes, hypertension, smoking, renal failure, and plasma
      cholesterol. No difference was found in the incidence and/or level of any of
      these risk factors when patients with normal plasma homocyst(e)ine were compared
      to those with elevated plasma homocyst(e)ine, both by univariate and multivariate
      analysis. Patients with elevated plasma homocyst(e)ine were more likely to
      demonstrate clinical progression of lower extremity disease and of coronary
      artery disease, but not of cerebral vascular disease than were patients with
      normal plasma homocyst(e)ine, and the rate of progression was more rapid (p =
      0.002). Progression of lower extremity disease as assessed in the vascular
      laboratory was also more common in patients with elevated plasma homocyst(e)ine
      (p = 0.01). We conclude that elevated plasma homocyst(e)ine is an independent
      risk factor for symptomatic lower extremity disease or cerebral vascular disease
      or both. Symptomatic patients with lower extremity disease and with elevated
      plasma homocyst(e)ine also appear to have more rapid progression of disease.

PMID- 1987385
TI  - Experience with in situ saphenous vein bypasses during 1981 to 1989: determinant
      factors of long-term patency.
AB  - From 1981 to 1989, 361 consecutive in situ saphenous vein bypasses were
      performed. Indications for revascularization were critical limb ischemia (n =
      335, 93%), popliteal aneurysm (n = 15, 4%), and claudication (n = 11, 3%).
      Outflow tract was the popliteal artery in 116 (32%) and tibial artery in 245
      (68%) of bypasses. At 6 years primary patency was 63% and secondary patency was
      81%. During the performance of the in situ bypass procedure, 86 (24%) venous
      conduits were modified because of a technical failure (n = 49, 13%) or an
      inadequate vein segment (n = 37, 10%). Secondary patency at 4 years for bypasses
      requiring modification was 72% compared to 84% for bypasses not modified (p less
      than 0.05). Atherosclerotic disease of the inflow artery necessitating
      endarterectomy, patch angioplasty, or replacement lowered primary patency at 3
      years (69%) compared to the inflow artery not requiring reconstruction (46%, p
      less than 0.02). In the follow-up period, 95 (26%) bypasses were revised because
      of thrombosis or hemodynamic failure. Bypasses requiring revision had a 4-year
      secondary patency of 68% compared to 88% for bypasses not revised (p less than
      0.02). The first 179 cases (1981 to 1985) were compared to the subsequent 182
      cases (1986 to 1989). The secondary patency at 3 years for the latter half (92%)
      compared to the first half (80%) of the experience was significantly improved (p
      less than 0.02). The secondary patency for bypasses not requiring revision was
      significantly improved (p less than 0.02) for the latter half (n = 142, 97%)
      compared to the first half (n = 124, 83%) of the series. Long-term patency with
      the in situ saphenous vein bypass is dependent on surgical experience, quality of
      the venous conduit, and atherosclerotic disease of the inflow artery that
      necessitates reconstruction. Meticulous surgical technique and compulsive bypass
      surveillance results in superior long-term patency.

PMID- 1987386
TI  - Treatment of abdominal aortic aneurysm by exclusion and bypass: an analysis of
      outcome.
AB  - Abdominal aortic aneurysm is conventionally treated by aneurysmorrhaphy with
      inlying graft. Alternatively, division of the aorta, with suture closure of the
      distal aorta and outflow vessels (exclusion of the aneurysm), and end-to-end
      proximal to distal bypass may be performed. However, the long-term fate of this
      operation has not been determined. Specifically, concern exists that the excluded
      blood filled aneurysm may not thrombose or may be the source of late sepsis.
      During an 8-year period we have treated 280 abdominal aortic aneurysms (urgent
      and elective) by exclusion of the abdominal aortic aneurysm sac and bypass via
      the posterolateral retroperitoneal approach. Mean age was 70 years (range, 44 to
      88), with 217 men and 63 women. Preoperative CT scanning and aortography were
      performed to assess arterial anatomy. Seventy tube grafts and 260 bifurcation
      grafts were used. Thirty-day mortality rate was 4%. Estimated blood loss was 731
      +/- 52 ml; mean transfusion requirements were 456 +/- 82 ml. The minor
      complication rate was 6%, and it is of great interest that there were no cases of
      ischemic colitis requiring colectomy. Aneurysm sacs thrombosed except in two
      anticoagulated patients who required further treatment. No late infections
      occurred. Five-year bypass patency rate was 98%. These data demonstrate that this
      method of treatment effectively minimized operative dissection and blood loss and
      therefore is a viable alternative for the management of abdominal aortic
      aneurysms.

PMID- 1987387
TI  - Antiplatelet drugs in femoropopliteal vein bypasses: a multicenter trial.
AB  - To evaluate the influence of antiplatelet drugs on patency in femoropopliteal
      vein bypasses, 48 vascular surgeons recruited 549 patients to a randomized double
      blind trial of aspirin (300 mg) + dipyridamole (150 mg) or placebo twice daily
      starting 2 days before surgery and continuing indefinitely. Graft occlusion
      measured objectively by independent coordinators and cardiovascular events
      (myocardial infarction or stroke) were studied, expressed by life table, and
      analyzed statistically by log rank and confidence intervals (95% CI).
      Randomization achieved comparable groups with 60% of grafts inserted for rest
      pain or gangrene. Operative complications on aspirin plus dipyridamole included
      18 reoperations for bleeding and 12 hematomas compared with 9 and 14,
      respectively, on placebo (NS). Most of the 172 graft failures occurred early with
      failure rates of 43/1000 patient-months in the first 3 months, reducing to
      17/1000 at 6 to 12 months, and under 10/1000 in subsequent years. Cumulative
      graft patency on placebo was 72%, 62%, and 60% at 1, 2, and 3 years,
      respectively, compared with 78%, 70%, and 61% on aspirin plus dipyridamole. The
      difference in patency of 6.1% (95% CI, -3% to 15.5%) at 1 year and 8.0% (95% CI, 
      5% to 21%) at 2 years failed to achieve significance (p = 0.43). On mean follow
      up of 34 months, 53 (132/1000 patient-years) cardiovascular events (myocardial
      infarction or cerebrovascular accident) occurred in patients on placebo compared
      with only 35 (73/1000) on aspirin plus dipyridamole, a significant difference of
      59/1000 (p = 0.004). Antiplatelet therapy had little influence on femoropopliteal
      vein patency, but subsequent myocardial infarction and stroke was reduced in
      these patients with peripheral vascular disease.

PMID- 1987389
TI  - Comparison of ejection fraction and Goldman risk factor analysis to dipyridamole
      thallium 201 studies in the evaluation of cardiac morbidity after aortic aneurysm
      surgery.

PMID- 1987388
TI  - Prospective, randomized comparison of ringed and nonringed
      polytetrafluoroethylene femoropopliteal bypass grafts: a preliminary report.
AB  - Kinking and compression with knee flexion are thought to be one cause of failure
      of below-knee polytetrafluoroethylene femoropopliteal bypass. To prevent this
      problem polytetrafluoroethylene grafts externally supported with rigid rings have
      been developed. The present randomized, prospective study compared ringed and
      nonringed polytetrafluoroethylene grafts in 122 patients who underwent
      femoropopliteal bypass for severe limb ischemia. Patients were well matched for
      surgical indications and risk factors. There was no significant difference in the
      3-year graft patency rate of ringed versus nonringed polytetrafluoroethylene
      femoropopliteal bypasses (74% vs 68%, p = 0.5). Similarly, no significant
      differences were found in the 3-year graft patency rates of ringed versus non
      ringed above-knee (82% vs 74%, p = 0.5) or below-knee polytetrafluoroethylene
      femoropopliteal bypasses (68% vs 59%, p = 0.5). The 3-year graft patency rate of
      all above-knee polytetrafluoroethylene femoropopliteal bypasses was slightly
      greater than that of below-knee polytetrafluoroethylene femoropopliteal bypasses
      (76% vs 62%), but this difference was not statistically significant (p = 0.25).
      The 3-year limb salvage rate with ringed polytetrafluoroethylene grafts was 92%
      compared with 79% for nonringed polytetrafluoroethylene grafts, but this
      difference was not statistically significant (p = 0.25). Data to date from this
      study fail to support the recommendation that ringed polytetrafluoroethylene
      grafts be used preferentially over conventional polytetrafluoroethylene grafts in
      patients who require femoropopliteal bypass with a synthetic graft.

PMID- 1987390
TI  - Resting gated pool ejection fraction: a poor predictor of perioperative
      myocardial infarction in patients undergoing vascular surgery for infrainguinal
      bypass grafting.

PMID- 1987391
TI  - Neurologic sequelae of unilateral carotid artery occlusion: immediate and rare.

PMID- 1987392
TI  - Histogenesis of intimal hyperplasia and arterial dissection.

PMID- 1987393
TI  - Angiographic localization of spinal cord blood supply and its relationship to
      postoperative paraplegia.
AB  - Forty-seven patients underwent selective catheterization of middle and lower
      thoracic intercostal and upper lumbar arteries to define the origin of the artery
      of Adamkiewicz. One patient had significant atheroembolism, and a second had
      transient lower extremity paresthesias. No other complications occurred. The
      origin was found in 26 (55%), and 21 patients underwent thoracoabdominal aneurysm
      repair with this knowledge. When the critical lumbar or intercostal artery could
      be included as part of a long proximal or distal anastomosis, all 12 patients
      could be included as part of a long proximal or distal anastomosis, all 12
      patients survived, and one was paralyzed. However, if the aneurysm repair
      mandated a midgraft anastomosis to intercostal arteries critical to spinal cord
      perfusion, seven of nine patients either died or were paralyzed (p less than
      0.05). In the group of 19 patients operated on in whom spinal cord blood supply
      was not identified three patients had a technically unsuccessful operation; two
      died, and one was paralyzed. Twelve of 16 patients who had an adequate, but
      unsuccessful attempt at localization were treated by intercostal "neglect" and
      survived. Late paresis developed in two patients, but they are walking now. One
      of the patients who died had multiple systems failure and awakened paraplegic.
      She had a patent, enlarged, thoracic radicular artery at T-5 which probably
      supplied to spinal cord and which was missed angiographically. Paralysis was
      associated with aneurysm extent (group 2 and III B, dissections vs group 1 & 3, p
      less than 0.05). Selective intercostal angiography requires further refinement,
      but it is safe and offers the promise of understanding the mechanisms and risks
      of spinal cord complications after repair of extensive thoracoabdominal
      aneurysms.

PMID- 1987394
TI  - D. Emerick Szilagyi, MD--an appreciation.

PMID- 1987395
TI  - A prospective randomized study of cerebrospinal fluid drainage to prevent
      paraplegia after high-risk surgery on the thoracoabdominal aorta.
AB  - This article is concerned with the study of the effect of several variables,
      principally that of cerebrospinal fluid drainage, on the incidence of neurologic
      deficit in a prospective randomized series of patients with extensive aneurysms
      of the descending thoracic and abdominal aorta (thoracoabdominal type I and II).
      Forty-six patients had cerebrospinal fluid drainage, and 52 were controls, with a
      total of 98 available for study. Cerebrospinal fluid pressure was continuously
      monitored in the former group and pressure maintained less than or equal to 10 mm
      Hg in 20, less than or equal to 15 mm Hg in 20, and greater than 15 mm Hg in 6
      patients during period of aortic clamping. The method of treatment including
      reattachment of intercostal and lumbar arteries (p = 0.2), temporary atriofemoral
      bypass during aortic occlusion (p = 0.3), and spinal fluid drainage (p = 0.8)
      were not statistically significant in reducing the incidence of neurologic
      deficits. Thus cerebrospinal fluid drainage as we used it, was not beneficial in
      preventing paraplegia. On appropriate statistical analysis we found that the only
      significant predictor of delayed deficits was postoperative hypotension (p =
      0.006).

PMID- 1987396
TI  - Arterial aneurysms in children: clinicopathologic classification.
AB  - Thirty-one arterial macroaneurysms in 23 pediatric-aged patients (16 boys and 7
      girls) were treated at the University of Michigan. The average age at time of
      diagnosis was 10.2 years (range 6 months to 18 years). Vessels involved the aorta
      (4), as well as hepatic (1), splenic (2), gastroepiploic (1), renal (12), iliac
      (1), superficial femoral (4), popliteal (1), brachial (1), radial (2), and ulnar
      (2) arteries. Twelve children exhibited overt clinical manifestations including
      presence of a mass (7), local pain (3), hematemesis (1), and painless obstructive
      jaundice (1). Eleven children had asymptomatic lesions. Aneurysm existence was
      confirmed by arteriography or operation. All but one child underwent surgical
      therapy, with 20 long-term survivors (mean follow-up 3.5 years). One operative
      death occurred and one death occurred 6 years after surgery. This experience and
      a review of previously reported cases served as a basis for categorization of
      childhood aneurysmal disease as true aneurysms associated with (I) arterial
      infection, (II) giant-cell aortoarteritis, (III) autoimmune connective tissue
      disease, (IV) Kawasaki's disease, (V) Ehlers-Danlos syndrome or Marfan's
      syndrome, (VI) other forms of noninflammatory medial degeneration, (VII) arterial
      dysplasias, (VIII) congenital-idiopathic factors, as well as (IX) false aneurysms
      associated with extravascular events causing vessel wall injury or disruption.
      Knowledge of the varied clinicopathologic characteristics of arterial aneurysms
      in children is important in treating these patients.

PMID- 1987397
TI  - Who sets the standards?

PMID- 1987398
TI  - Penile duplex sonography in the diagnosis of venogenic impotence.
AB  - This study tested the hypothesis that measurements of cavernous arterial
      diastolic velocity and resistance index could provide a quantitative but
      noninvasive measure of penile corporal venous leakage. Seventy-four men were
      studied with duplex ultrasonography after intracavernosal injection of 60 mg of
      papaverine. Fourteen men had normal erection and served as controls. Sixty men
      had a 1-year history of transient fading or incomplete erections. In all subjects
      the peak systolic velocity and end-diastolic velocity were measured, and the
      resistance index was calculated (peak systolic velocity--end-diastolic
      velocity/peak systolic velocity). Men with normal erections had peak systolic
      velocities greater than 35 cm/sec and end-diastolic velocities less than 4.5
      cm/sec (group 1). Patients with incomplete erections (group II) could be
      classified into three subgroups. Twenty-three patients with end-diastolic
      velocities greater than 4.5 cm/sec and normal peak systolic velocities greater
      than 35 cm/sec were suspected to have corporal venous leakage (group A). Eighteen
      patients had normal end-diastolic velocities less than 4.5 cm/sec. Twelve of this
      group had peak systolic velocities less than 35 cm/sec, and six had peak systolic
      velocities ranging from 37 to 44 cm/sec. These patients were suspected of having
      arterial insufficiency (group B). Fifteen patients with end-diastolic velocities
      greater than 4.5 cm and peak systolic velocities less than 35 cm were suspected
      of having both venous leakage and arterial insufficiency (group C). Twenty-one
      patients with abnormal diastolic flow underwent infusion pharmacocavernosometry
      to determine the saline maintenance infusion rate necessary to maintain an
      intracavernosal pressure of 90 to 100 mm Hg or a full erectile response.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1987400
TI  - Ultrasound screening of first-degree relatives of patients with an abdominal
      aortic aneurysm.
AB  - The pedigrees were constructed of 43 patients (probands) who underwent resection
      of an abdominal aortic aneurysm. Seven probands (16.2%) had a first-degree
      relative (parent, sibling, child) known to have had an abdominal aortic aneurysm
      (multiplex family). To determine the prevalence of undiagnosed abdominal aortic
      aneurysm, ultrasound screening of first-degree relatives over age 40 years was
      undertaken. Of 202 eligible relatives, 103 (51.0%) were screened. An occult
      abdominal aortic aneurysm was defined as an infrarenal aortic diameter greater
      than 3.0 cm or an infrarenal/suprarenal aortic diameter ratio of greater than
      1.5. An incipient abdominal aortic aneurysm was defined as a clear focal bulge of
      the infrarenal aorta, which was less than 3.0 cm in greatest diameter. Four of
      103 relatives (3.9%) were found to have an occult abdominal aortic aneurysm
      (age/sex: 57M, 60M, 62F, 65M), and three (2.9%) were found with an incipient
      abdominal aortic aneurysm (age/sex: 56M, 60M, 67F). These smaller abdominal
      aortic aneurysms were in patients younger than the operated probands (average age
      men, 67 years; women, 69 years). Six of seven individuals were in families
      previously considered simplex, increasing the actual multiplex family frequency
      from 16.2% to 27.9%. All seven new abdominal aortic aneurysms were found in the
      49 siblings age 55 years or older. There were no abdominal aortic aneurysms found
      in the 39 relatives under age 55 years, in 14 children ages 50 to 59 years or in
      one parent. Therefore of the siblings age 55 years or older, 5/20 men (25.0%) and
      2/29 women (6.9%) were found to have a previously undiagnosed abdominal aortic
      aneurysm.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1987401
TI  - Physicians provide continuum of care for Desert Storm fighting forces.

PMID- 1987399
TI  - Mesenteric blood flow in patients with diabetic neuropathy.
AB  - We examined flow velocities in the superior mesenteric artery and celiac artery
      in normal controls (group C, n = 11), diabetic patients (group D, n = 8), and
      diabetic patients with clinically evident autonomic neuropathy (group DN, n = 6)
      to further define the usefulness of duplex examination in the evaluation of the
      mesenteric circulation in normal and disease states. By use of a 3 MHz duplex
      scanner, peak systolic velocity, peak diastolic forward velocity, end-diastolic
      forward velocity, and peak diastolic reverse velocity were measured in
      centimeters per second before and after a standardized meal. The vessels'
      diameters in centimeters were also measured. After the meal peak diastolic
      reverse velocity disappeared in all patients. The average vessel diameter in the
      superior mesenteric artery (0.7 cm) and celiac artery (0.8 cm) did not change.
      Flow velocities in the celiac artery were not significantly altered by the meal.
      In the control group, peak systolic velocity in the superior mesenteric artery
      increased 38%, peak diastolic forward velocity rose 66%, and end-diastolic
      forward velocity increased by 70%. In the diabetic nonneuropathic group the
      changes were 15%, 98%, and 100%, respectively. These changes were statistically
      significant (p less than 0.01). On the other hand, the patients with diabetic
      autonomic neuropathy presenting a picture of gastroparesis did not exhibit the
      expected increases in postprandial velocities. Moreover, this alteration in blood
      flow velocity, although similar to that encountered in patients with intestinal
      angina, did not appear to be due to occlusive arterial disease on the basis of
      clinical examination and B-mode scanning.

PMID- 1987402
TI  - Mental health professionals find fewer problems than expected in Desert Storm.

PMID- 1987403
TI  - Service in strict islamic nation removes alcohol, other drugs from major problem
      list.

PMID- 1987404
TI  - From the Centers for Disease Control. Update: transmission of HIV infection
      during an invasive dental procedure--Florida.

PMID- 1987405
TI  - A piece of my mind. Deserted island.

PMID- 1987407
TI  - The Medics' War: what happened at Chipyong-ni.

PMID- 1987406
TI  - Cesarean section rates.

PMID- 1987408
TI  - HTLV seroreactivity in Italian intravenous drug addicts is primarily due to HTLV
      II infection.

PMID- 1987409
TI  - The association of skin color with blood pressure in US blacks with low
      socioeconomic status.
AB  - To determine the association of skin color, measured by a reflectometer, with
      blood pressure in US blacks, we studied a community sample of 457 blacks from
      three US cities. Persons taking antihypertensive medications were excluded. Both
      systolic and diastolic blood pressure were higher in darker persons and increased
      by 2 mm Hg for every 1-SD increase in skin darkness. However, the association was
      dependent on socioeconomic status, whether measured by education or an index
      consisting of education, occupation, and ethnicity, being present only in person
      with lower levels of either indicator. Using multiple linear regression, both
      systolic and diastolic blood pressure remained significantly associated with
      darker skin color in the lower levels of socioeconomic status, independent of
      age, body mass index, and concentrations of blood glucose, serum urea nitrogen,
      serum uric acid, and urinary sodium and potassium. The association of skin color
      with blood pressure only in low socioeconomic strata may be due to the lesser
      ability of such groups to deal with the psychosocial stress associated with
      darker skin color. However, these findings also are consistent with an
      interaction between an environmental factor associated with low socioeconomic
      status and a susceptible gene that has a higher prevalence in persons with darker
      skin color.

PMID- 1987410
TI  - Efficacy of bladder training in older women with urinary incontinence.
AB  - The efficacy of bladder training was evaluated in a randomized clinical trial
      involving 123 noninstitutionalized women 55 years and older with urinary
      incontinence. Subjects were urodynamically categorized as those with urethral
      sphincteric incompetence (N = 88) and those with detrusor instability with or
      without concomitant sphincteric incompetence (N = 35). Bladder training reduced
      the number of incontinent episodes by 57%; the effect was similar for both
      urodynamic diagnostic groups. The quantity of fluid loss was reduced by 54%. This
      was greater for patients with detrusor instability than for those without it.
      Diurnal and nocturnal voluntary micturitions were also reduced. The effect on
      nocturnal micturition, however, was not observed in subjects with unstable
      detrusor function. It is recommended that bladder training be considered as an
      initial step in treatment of women with urinary incontinence. Provided prior
      comprehensive clinical evaluation is done, it can be prescribed without the need
      for urodynamic characterization.

PMID- 1987411
TI  - Cigarette smoking increases the risk of albuminuria among subjects with type I
      diabetes.
AB  - The effect of cigarette smoking on diabetic renal and retinal complications was
      evaluated in 359 young subjects with insulin-dependent diabetes mellitus. The
      prevalence of increased albumin excretion rates was 2.8 times higher in smokers
      than nonsmokers. Mean glycohemoglobin levels and duration of diabetes were also
      significant factors in the development of diabetic nephropathy and retinopathy in
      a logistic regression model. Smoking remained a significant factor in the
      logistic regression model for albuminuria (but not retinopathy) when controlled
      for glycohemoglobin level, duration of diabetes, age, gender, and blood pressure.
      The progression of albuminuria and of retinopathy was also greater in smokers.
      Albuminuria improved significantly when subjects ceased smoking. It is concluded
      that cigarette smoking is an independent risk factor and is associated with the
      development and progression of early diabetic renal damage (albuminuria) and with
      the worsening of retinal disease in young subjects with diabetes.

PMID- 1987412
TI  - Driving and epilepsy. A review and reappraisal.
AB  - Driving and epilepsy is a problem that involves physicians as both care providers
      to patients and consultants to regulatory authorities. Driving restrictions for
      people with seizure disorders are intended to ensure the public's safety, but
      such restrictions may unduly harm the welfare of many people with seizures. In
      the United States, all states now permit some people with epilepsy to drive. In
      general, only people whose seizures are adequately controlled are licensed to
      drive. Adequate control has been judged principally by the seizure-free interval,
      but individual state standards widely vary. There is a trend toward greater
      liberalization of driving standards for people with seizure disorders, but the
      appropriateness and application of these standards continue to raise questions,
      as does the role physicians should have in the licensing process. Our
      responsibilities to persons with disabilities and advances in our understanding
      of seizures and the nature of driving risks warrant a reappraisal of the current
      medical, legal, and social implications of driving and epilepsy.

PMID- 1987414
TI  - A successful treatment of an intrarenal arteriovenous fistula by percutaneous
      embolization.
AB  - A 37-year-old woman patient, known to have poorly controlled arterial
      hypertension that was diagnosed following a cerebrovascular accident at the age
      of 15 years, was referred to our outpatient clinic for investigation in 1987. An
      intrarenal arteriovenous fistula was diagnosed by selective renal angiography.
      Embolization of the fistula was performed using four 15-mm/5-cm coils, which
      induced thrombosis and obstructed the fistula. The vascularization of the
      affected kidney improved immediately. During the following 4 months, the
      antihypertensive treatment was stopped gradually, and the patient remained
      normotensive. This is an unusual case of a large intrarenal arteriovenous
      fistula, whose etiology was not clear, that was successfully treated by
      percutaneous embolization.

PMID- 1987413
TI  - Why is diabetes mellitus a stronger risk factor for fatal ischemic heart disease
      in women than in men? The Rancho Bernardo Study.
AB  - We report here the 14-year sex-specific effect of non-insulin-dependent diabetes
      mellitus on the risk of fatal ischemic heart disease in a geographically defined
      population of men and women aged 40 through 79 years. There were 207 men and 127
      women who had diabetes at baseline based on medical history or fasting
      hyperglycemia. They were compared with 2137 adults who had fasting euglycemia and
      a negative personal and family history of diabetes. The relative hazard of
      ischemic heart disease death in diabetics vs nondiabetics was 1.8 in men and 3.3
      in women, after adjusting for age, and 1.9 and 3.3, respectively, after adjusting
      for age, systolic blood pressure, cholesterol, body mass index, and cigarette
      smoking using the Cox regression model. The sex difference in the independent
      contribution of diabetes to fatal heart disease was largely explained by the
      persistently more favorable survival rate of women (than men) without diabetes.

PMID- 1987415
TI  - Pharmacologic stress imaging.
AB  - Pharmacologic stress imaging has increasingly been employed as an alternative to
      exercise imaging for detection of coronary artery disease and risk stratification
      particularly in patients who are unable to perform adequate exercise. Sensitivity
      and specificity of thallium 201 scintigraphy using intravenous dipyridamole
      infusion as a stress for coronary artery disease detection average 85% and 91%,
      respectively. Dipyridamole imaging is also useful for differentiating between
      ischemia and scar and identifying patients who have an increased risk for
      subsequent cardiac events. Dipyridamole imaging is particularly useful for
      preoperative risk stratification in patients undergoing surgery for peripheral
      vascular or aortic disease. Dipyridamole imaging is also useful for identifying
      residual myocardial ischemia after myocardial infarction and detecting restenosis
      after coronary angioplasty. Adverse side effects of dipyridamole are promptly
      reversed by aminophylline. Dipyridamole stress can also be employed in
      association with echocardiography for detection of ischemia-induced regional wall
      motion abnormalities.

PMID- 1987417
TI  - Answering the call.

PMID- 1987416
TI  - Skin color and blood pressure. Genetics or environment?

PMID- 1987418
TI  - Exercise-associated urticaria.

PMID- 1987419
TI  - Submandibular Calculi.

PMID- 1987420
TI  - Sudden visual loss following cataract removal.

PMID- 1987421
TI  - Hyperhidrosis.

PMID- 1987422
TI  - The hand that feeds.

PMID- 1987423
TI  - Pharmaceutical funding and medical students.

PMID- 1987424
TI  - Medical education in the Soviet Union.

PMID- 1987425
TI  - India's medical dilemma: overpopulation and underfunding.

PMID- 1987426
TI  - Financing education: greater need, less aid.

PMID- 1987427
TI  - The specificity of lymphokine-activated killer (LAK) cells in vitro: fresh normal
      murine tissues are resistant to LAK-mediated lysis.
AB  - We have previously reported that murine splenocytes incubated in the lymphokine
      interleukin-2 acquire the ability to mediate the lysis of a variety of fresh
      tumor cells in short-term chromium-51 release assays. This study was designed to
      evaluate the effect of lymphokine-activated killer (LAK) cells on fresh normal
      murine tissues. The susceptibility to lysis by LAK cells of single cell
      suspensions from a variety of murine tissues including lung, kidney, bone marrow,
      peripheral blood mononuclear cells, intestinal mucosa, liver, and fetus was
      studied. While kidney, intestinal mucosa, and peripheral blood mononuclear cells
      were clearly not lysed, there was a very low level of lysis of lung, bone marrow,
      liver, and fetus in repeated experiments. Separation of the cell suspensions of
      lung and bone marrow demonstrated much higher lysis of the adherent cell
      population, corresponding to an increased number of macrophages in the target
      cell suspension. Macrophages represent a population of cells particularly
      sensitive to lysis by LAK cells. All of the normal tissues were highly lysable by
      LAK cells in antibody-dependent cellular cytotoxicity assays in the presence of
      the appropriate anti-H-2 antibody. In a series of cold target inhibition studies,
      fresh normal murine kidney, lung, and bone marrow did not inhibit the lysis of
      the LAK-sensitive tumor target MCA-102, further demonstrating that fresh normal
      tissues share little if any of the determinant recognized by LAK cells on tumor
      targets. However, the MCA-105 and MCA-106 tumors, and the YAC cell line, all of
      which are sensitive to LAK cell lysis, did inhibit the lysis of MCA-102 tumor.
      These studies suggest that a common determinant is present on LAK-sensitive
      tissues that is absent or present in very low amounts on fresh normal tissues.

PMID- 1987428
TI  - Effects of ischemia on epicardial segment shortening.
AB  - To evaluate the effects of nontransmural ischemia on epicardial contractile
      function, we implanted sonomicrometers in 15 open-chest, anesthetized (halothane)
      dogs. One cylindrical crystal (radiating ultrasound 360 degrees) was used as a
      transmitter for three conventional flat plate crystals arrayed to measure
      epicardial segment shortening along three different axes that were deviated 0
      degree (parallel), 45 degrees (oblique), and 90 degrees (perpendicular) from
      surface fiber orientation in the anteroapical or posterior-basal left ventricle.
      During baseline conditions, epicardial shortening was maximal parallel with fiber
      orientation. Shortening decreased in a non-linear manner as deviation from fiber
      orientation increased, but there were significant differences between the two
      left ventricular regions suggesting that more substantial lateral strain occurs
      in the anterior-apical than the posterior-basal area. During coronary inflow
      restriction, changes in epicardial segment shortening also varied greatly
      depending on location and alignment. At levels of wall thickening impairment
      associated with normal subepicardial perfusion, changes in epicardial function
      were restricted to the segments aligned perpendicular to fiber orientation
      whereas the parallel and oblique segments displayed moderate dysfunction or none
      at all. Thus, transmural tethering modifies epicardial segmental motion during
      coronary inflow restriction, but the severity of the influence depends on the
      alignment and location of the epicardial measurements.

PMID- 1987429
TI  - Enhanced survival of IFN-alpha augmented IL-2 therapy of pulmonary metastases:
      efficacy comparable to interleukin-2 and lymphokine activated killer cells.
AB  - Recently, we reported enhanced tumor reduction using recombinant interferon-alpha
      A/D (IFN) combined with interleukin-2 (IL-2). Similar synergism affecting
      survival was assessed in treatment of both early and advanced pulmonary
      metastases. This combination was compared with the current "standard" IL-2 and
      lymphokine activated killer (LAK) therapy in the treatment of early and advanced
      pulmonary metastases. C57BL/6 mice injected via tail vein with the weakly
      immunogenic methylcholanthrene-induced murine fibrosarcoma MCA-106 were treated
      intraperitoneally with IL-2 (50,000 units b.i.d.), IFN (50,000 units q.d.), LAK
      (2.5-10 x 10(7)), or various combinations of above. Treatment of both early Day 3
      and advanced Day 10 metastases using IL-2/IFN reduced metastases and prolonged
      survival over both controls and IL-2 alone. It was superior to IFN, LAK, and
      IFN/LAK. Addition of LAK to IL-2/IFN demonstrated no added benefit. Although no
      mortality was observed during treatment of Day 3 metastases, treatment of Day 10
      advanced pulmonary metastases for 9 days with IL-2/IFN resulted in early deaths
      (33%) without visible tumor, indicating possible toxicity of treatment. These
      results show survival benefit of IL-2/IFN over IL-2, IFN, or LAK treatment in the
      therapy of early and advanced pulmonary metastases, albeit with added toxicity.
      Its relative simplicity and comparable efficacy to the more complex and costly IL
      2/LAK provide important advantages for potential clinical applications.

PMID- 1987430
TI  - Effect of bFGF on the inhibition of contraction caused by bacteria.
AB  - Bacterial contamination of open wounds significantly inhibits wound contraction
      required in the healing process. Basic fibroblast growth factor (bFGF) has been
      shown to overcome contraction inhibition in wound-healing models impaired by
      diabetes or steroids. This study was designed to determine the effect of bFGF on
      wound contraction inhibition in an area contaminated with bacterial overgrowth.
      The topically applied bFGF reversed inhibition to wound contraction that normally
      occurs with bacterial contamination. This reversal does not appear to be due to
      increased collagen synthesis since bFGF has been shown to decrease collagen
      synthesis and the treated wounds showed no increase in breaking strength. The use
      of bFGF significantly decreased the number of days required for wound healing (P
      less than 0.01) despite active bacterial invasion and may be of value in the
      treatment of human contaminated wounds.

PMID- 1987431
TI  - Palmitate and stearate kinetics in the rat during sepsis and trauma.
AB  - Kinetics of plasma free palmitate and stearate were measured in control and
      septic-traumatized rats to determine the contribution plasma free fatty acids
      make to increased resting energy expenditure. Measurements were made at 24 hr
      after insult using a primed, 4-hr continuous infusion of selected (1-14C) fatty
      acid. The plasma concentration of palmitate was increased and stearate was
      decreased in sepsis-trauma rats compared to plasma concentrations in healthy
      control rats. Fatty acid turnover rates during sepsis-trauma were changed from
      control turnover rates in the same direction as plasma concentrations. Oxidation
      rates for palmitate and stearate at 24 hr after induction of sepsis-trauma were
      not different from oxidation rates in control rats. Plasma free fatty acids were
      concluded not to exhibit increased oxidation after sepsis-trauma and not to
      contribute extra energy during hypercatabolism. This finding contrasts with
      glucose and amino acids which have an increased oxidation rate during
      hypercatabolism.

PMID- 1987432
TI  - Transplantation of cryopreserved canine venous allografts.
AB  - Local vascular reconstructions frequently require the use of vein grafts to
      bridge arterial or venous defects. Most previous studies on the use of
      cryopreserved veins have used relatively large caliber vessels. There have been
      few studies on the effectiveness of cryopreserved micro- or small-venous
      allografts. Here, we tested two types of cryopreserved venous allografts: (1) 1.5
      to 1.9-mm diameter microvenous grafts (MVG); and (2) 4- to 5-mm diameter small
      venous grafts (SVG). Cryopreserved MVG allografts were placed into saphenous
      arteries of six experimental dogs and SVG cryopreserved allografts were placed
      into femoral arteries of six experimental dogs for 3 to 6 weeks. Two fresh MVG
      autografts were also transplanted into experimental dogs as controls and
      autografts were transferred to the contralateral side in SVG dogs as controls.
      None of the six cryopreserved MVG grafts retained patency but three/six
      cryopreserved SVG allografts were patent at harvest. Histological examination of
      grfts revealed control autografts were undergoing arterialization with an intact
      intima. Experimental cryopreserved allografts showed extensive medial fibrosis,
      significant lymphocytic infiltrates, and sporadic areas of intact intima for both
      patent and nonpatent grafts.

PMID- 1987433
TI  - Specific growth factor activity identifies and predicts murine mammary tumor.
AB  - In milk from substrains of mice with varying incidences of developing mammary
      tumor, we have isolated a specific mitogenic activity, which is unique in that it
      identifies mice with mammary tumor and predicts those mice that will eventually
      develop mammary tumor. None of the milk samples from control mice, who never
      developed mammary tumor, contained this specific predictive mitogenic activity.
      Chemical characterization has shown this specific mitogenic activity to be acid-
      and heat-stable and resistant to reducing agents. Partial purification, by ion
      exchange, high-performance liquid chromatography size-exclusion, and
      isoelectrofocusing techniques, of this specific mitogenic activity from milk of
      mice that had or eventually developed mammary tumor identifies several peptide
      growth factor components in a 6-10 kDa molecular weight range. Of known growth
      factors, radioassay techniques identify an insulin-like growth factor-1-like
      peptide as a major component. Small amounts of platelet-derived growth factor and
      transforming growth factor-beta activities also were present. Our results suggest
      that a subset of growth factors that are diagnostic of the presence of murine
      mammary tumor and predictive of eventual tumor development may be early
      indicators of the transition of a competent cell to a progressively malignant
      state. Similar studies of a secreted body fluid from women at risk for breast
      cancer may lead to the identification of a specific biologic tumor marker for
      breast cancer.

PMID- 1987434
TI  - Alteration of gastric surface cell pH regulation by sodium taurocholate.
AB  - Gastric mucosal cells from guinea pigs were grown in cell culture. Acridine
      orange fluorescence at 624 nm was used as an qualitative indicator of
      intracellular pH. The cultured cells were exposed to Hank's solution at pH 7.4,
      6.0, 5.0, 4.0, 3.0, and 1.8 for 30 min. After removal of the acid, the cells were
      loaded with acridine orange for qualitative pH assessment. The cells developed
      alkaline shifts in the cytoplasmic pH in direct proportion to the acid load. This
      alkaline overcorrection after exposure to acid was blocked by amiloride and
      blunted by taurocholic acid in a dose-dependent fashion. These results suggest
      that gastric surface cells may regulate their cytoplasmic pH with a sodium
      hydrogen antiporter. These results also suggest that this antiport system may be
      adversely affected by bile salts.

PMID- 1987435
TI  - Attenuation of the pulmonary vascular response to endotoxin by a thromboxane
      synthesis inhibitor (UK-38485) in unanesthetized sheep.
AB  - Previous studies have documented the phasic pulmonary vascular response to
      infused Escherichia coli endotoxin in unanesthetized sheep. Cyclooxygenase
      inhibition attenuates the initial vasoconstrictive phase (phase I) but not the
      late phase of increased microvascular permeability (phase II). We undertook to
      selectively inhibit thromboxane A2 synthesis and assess the pulmonary
      microvascular response to endotoxin. Twelve paired studies were carried out in
      six sheep prepared with chronic lung lymph fistulas and pressure monitoring
      catheters. Each sheep received E. coli endotoxin (0.5 microgram/kg) at time 0,
      both alone (control group) and 1 hr after pretreatment with a thromboxane
      synthetase inhibitor (UK-38485, 2 mg/kg). The animals were monitored for 1-2 hr
      prior to and 5 hr following endotoxin infusion to ensure a steady-state baseline
      and a complete late response. The pairs of studies were done in random order. In
      the presence of UK-38485, endotoxin caused significantly less pulmonary
      hypertension and shorter duration of leukopenia and lower lung lymph flow and
      lymph protein clearance rates than did endotoxin alone. The differences in lymph
      protein clearance were more pronounced in phase II. These data suggest that both
      the vasoconstrictive and permeability phases of the pulmonary vascular response
      to endotoxin may be modified on endogenous thromboxane A2.

PMID- 1987436
TI  - Ammonia elimination as a rapid index of viability in liver grafts in dogs.
AB  - We examined intraoperative changes in blood ammonia levels and the correlation
      with graft viability in orthotopic liver transplantation (OLTx) in 29 dogs. Blood
      ammonia levels following total hepatectomy were examined using five dogs. These
      levels immediately following hepatectomy (15 min) were significantly higher (212
      +/- 29 micrograms/dl) over values noted before hepatectomy (93 +/- 11
      micrograms/dl, P less than 0.05). OLTx was performed using the cuff technique.
      The animals were divided into two groups: Group A (n = 6 pairs), OLTx with a
      nonpreserved fresh graft; Group B (n = 6 pairs), OLTx with an 8-hr preserved
      graft with lactated Ringer (4 degrees C). In both groups, the blood ammonia
      levels before the surgery and at the anhepatic phase data did not differ;
      however, following reperfusion, the levels in Group B were significantly higher
      (211 +/- 26 at 15 min, 200 +/- 50 micrograms/dl at 30 min) than those in Group A
      (121 +/- 10 at 15 min; P less than 0.01, 109 +/- 9 micrograms/dl at 30 min; P
      less than 0.05). The blood ammonia level highly correlated with adenosine
      triphosphate contents in the liver tissue, blood level of lactic acid, and amount
      of bile output, all pertinent indicators of the graft viability. Thus, the
      potential to eliminate ammonia immediately after reperfusion can serve as an
      indicator of graft viability. The intraoperative monitoring of blood ammonia
      levels can be included in management guidelines in cases of liver
      transplantation.

PMID- 1987437
TI  - Right ventricular pump dysfunction with acute experimental septic shock.
AB  - Right ventricular (RV) function has been poorly characterized at the onset of
      acute bacterial septic shock. Using a volumetric thermodilution catheter,
      previously validated in our laboratory, we serially measured RV function in a
      porcine model of acute septic shock. Six pigs (21.3 +/- 0.9 kg) were instrumented
      and Pseudomonas aeruginosa (3.4 x 10(8) cfu/ml, 0.3 ml/20 kg/min) was infused. RV
      ejection fraction, RV volumes, cardiac output, arterial pressure, central venous
      pressure, and pulmonary arterial pressure were measured at baseline and at 30,
      60, 120, and 240 min after starting the bacterial infusion. RV ejection fraction
      and stroke volume were decreased at 30 min compared to baseline (21 +/- 5 vs 43
      +/- 5% and 14 +/- 3 vs 23 +/- 3 ml, respectively; P less than 0.05) and remained
      depressed throughout the experiment. Mean arterial pressure was significantly
      reduced at 60, 120, and 240 min compared to baseline (P less than 0.05). There
      was a significant increase in pulmonary vascular resistance (1771 +/- 493 vs 301
      +/- 99 dyn-sec-cm-5 at 30 min; P less than 0.05) and RV stroke work (5.7 +/- 1.1
      vs 2.3 +/- 0.3 gm-m/beat at 30 min; P less than 0.05) while no significant change
      in RV end-diastolic volume or central venous pressure was observed. Thus, a
      decrease in RV pump performance was associated with an increase in afterload and
      no change in preload. These results suggest that severe RV pump dysfunction
      occurs early in acute septic shock. This was manifested by significant reductions
      in RV ejection fraction and increased in stroke work.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1987438
TI  - Effective laboratory evaluation of thyroid status.
AB  - This article focuses on recent developments in thyroid-related laboratory tests,
      including analytical methods, clinical utility, and limitations of TSH, FT4, T4,
      FT3/T3, thyroglobulin, and thyroid autoantibodies and the effective use of these
      tests in the diagnosis of various forms of hypothyroidism or hyperthyroidism, and
      the management of patients undergoing T4 replacement, T4 suppression, or
      antithyroid drug therapy.

PMID- 1987439
TI  - Thyroid disease and pregnancy.
AB  - Thyroid disease is common in younger women and may be a factor in reproductive
      dysfunction. This probably only applies to severe cases of hyper- or
      hypothyroidism. Once adequately treated, neither of these disorders significantly
      impacts on fertility. The key is to recognize and to treat thyroid disorders in
      the reproductive-age woman before conception. Thyroxine therapy and even
      antithyroid drug therapy should be continued during pregnancy as necessary.
      Pregnancy is a euthyroid state that is normally maintained by complex changes in
      thyroid physiology. The fetal and neonatal hypothalamic-pituitary-thyroid system
      develops independently, but it may be influenced by thyroid disease in the
      mother. Early pregnancy is characterized by an increase in maternal T4 secretion
      stimulated by hCG and an increase in TBG, resulting in the elevated total serum
      T4 in pregnancy. The debate continues as to whether maternal T4 is important in
      early or late fetal brain development. If so, the physiologic changes in thyroid
      hormone secretion and transport in early pregnancy would help to ensure that a
      sufficient amount of thyroid hormone was available. There is new evidence in
      human subjects that substantial maternal T4 can cross the placenta during
      pregnancy, and this may be particularly important when fetal thyroid function is
      compromised as a result of congenital hypothyroidism. Maternal and fetal/neonatal
      outcomes in pregnancy are adversely affected if severe hypothyroidism is
      undiagnosed or inadequately treated. Thyroid function tests should be obtained
      during gestation in women taking T4 and appropriate dose adjustments should be
      made for TSH levels outside a normal range. The TSH-receptor blocking antibodies
      from the mother are a recognized cause of congenital hypothyroidism in the fetus
      and neonate that can be permanent or transient. If neonatal hypothyroidism is
      detected through neonatal screening programs, and prompt and adequate T4
      replacement therapy is instituted as soon as possible following delivery,
      subsequent growth and development are usually normal. Paradoxically, pregnancy
      often has a favorable effect on the course of maternal Hashimoto's disease,
      although there is the risk of relapse postpartum. Pathophysiologic conditions of
      hCG secretion such as gestational trophoblastic disease and hyperemesis
      gravidarum may present as thyrotoxicosis in pregnancy, but the main cause of this
      syndrome is Graves' disease. The mainstay of treatment is antithyroid drugs and
      either propylthiouracil or methimazole may be used safely. Subtotal
      thyroidectomy, after medical control, is the alternative treatment, but
      radioiodine ablation is contraindicated.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1987440
TI  - Thyroid disease in the elderly.
AB  - As people in our society live longer, it is important for clinicians to know more
      about problems commonly seen in the elderly. Thyroid problems are especially
      important to understand because they do occur with rather high frequency, and
      their mode of presentation is frequently different from those seen in younger
      patients. The thyroid gland does undergo certain age-related changes in anatomy
      and physiology, but overall the thyroid is able to produce a normal amount of
      thyroid hormone throughout the years. Hypothyroidism is frequently difficult to
      diagnose in the elderly, because many of the symptoms of hypothyroidism can
      easily be confused with symptoms of aging. When hypothyroidism is looked for in
      large population studies of elderly patients, the incidence varies from 1% to as
      high as 17%, with women being more commonly affected than men, and subclinical
      hypothyroidism being more common than overt hypothyroidism. Virtually all cases
      of hypothyroidism are due to autoimmune thyroid disease, with most patients
      having measurable titers of thyroid autoantibodies. The therapy of hypothyroidism
      is done with extreme caution, as older patients are frequently very sensitive to
      the effects of excess thyroid hormone. In addition, the metabolism of thyroid
      hormone slows down with age, making the full replacement dose much less in an
      older patient than in a younger one. Hyperthyroidism is also quite common,
      occurring in from 0.5% to 3% of all elderly patients. The presentation is
      frequently atypical, as patients often lack the hyperdynamic symptomatology and
      instead have a more sedated, apathetic presentation. Weight loss and cardiac
      symptoms frequently predominate, and the presence of a goiter is frequently
      absent, making the diagnosis less obvious than in a younger patient. Therapy is
      usually radioactive iodine, after an adequate course of antithyroid drugs, to
      render the patient euthyroid. Thyroid nodules do occur with increasing frequency
      in the elderly, but most of them are not malignant. Fine-needle aspiration for
      cytology is very helpful in determining which patients should be referred for
      surgery. Well-differentiated cancers do predominate, but their course is
      frequently less predictable than in younger patients. Lymphoma of the thyroid and
      undifferentiated cancers do occur with increasing frequency in the elderly.
      Multinodular goiter, usually of longstanding, is frequently seen in elderly
      patients, and thyroid hormone suppressive therapy not only is not indicated but
      may contribute to exogenous hyperthyroidism.

PMID- 1987441
TI  - Iodine and thyroid disease.
AB  - Iodine is a requisite substrate for the synthesis of the thyroid hormones, the
      minimum daily requirement being about 50 micrograms. An autoregulatory mechanism
      within the thyroid serves as the first line of defense against fluctuations in
      the supply of iodine and also permits escape from the inhibition of hormone
      synthesis that a very large quantity of iodine induces (Wolff-Chaikoff effect and
      escape therefrom). Environmental iodine deficiency continues to be a significant
      public health problem worldwide, compounded in some geographic regions by the
      presence of other goitrogens in some staple foods. The pathologic consequences of
      severe iodine deficiency include endemic goiter, endemic cretinism, increased
      fetal and infant mortality, and an increased prevalence in the community of
      cognitive and neuromotor disabilities. The implementation of an iodization
      program prevents endemic cretinism and reduces the frequency of the other
      pathologic consequences of iodine deficiency. Iodine excess results principally
      from the use of iodine-containing medicinal preparations or radiographic contrast
      media. The pathologic consequences of iodine excess will ensue only when thyroid
      autoregulation is defective, in that escape from the Wolff-Chaikoff effect cannot
      occur, or when autoregulation is absent. Defective autoregulation characterizes
      the fetal and neonatal thyroid, Hashimoto's thyroiditis, radioiodine or
      surgically treated Graves' hyperthyroidism, the thyroid of patients with cystic
      fibrosis, and the thyroid that has been exposed to weak inhibitors of the organic
      binding of iodine. In these circumstances, the provision of excess iodine may
      lead to iodide goiter with or without hypothyroidism. Absent autoregulation may
      be a feature of longstanding multinodular goiter, and the provision of excess
      iodine in this circumstance may induce thyrotoxicosis (Jod-Basedow disease). The
      pathologic consequences of iodine excess will resolve when the source of iodine
      has been dissipated. In addition to its role in reversing iodine deficiency,
      iodine is used as adjunctive therapy for hyperthyroidism. By inhibiting the
      proteolytic release of iodothyronines from thyroglobulin, it induces a prompt
      slowing of thyroid hormone secretion. This effect is exploited in the treatment
      of thyrotoxic crisis or severe thyrocardiac disease. Iodine also reduces thyroid
      cellularity and vascularity and therefore is used in the preparation of the
      patient for thyroidectomy. Finally, by exploiting the failure of escape from the
      Wolff-Chaikoff effect, iodine may also be used in the early management of
      radioiodine-treated Graves' hyperthyroidism.

PMID- 1987442
TI  - Thyroid crises.
AB  - In the setting of characteristic features of thyrotoxicosis, the timely diagnosis
      and aggressive management of thyroid storm should result in a successful outcome.
      However, severe storm may lead to irreversible cardiovascular collapse,
      especially in the older patient who may have atypical features of thyrotoxicosis.
      The fundamental approach is prompt and optimal treatment in the emergency
      department once the presenting clinical features suggest its presence. Delay in
      the introduction of therapy while awaiting laboratory confirmation may result in
      further decompensation and death. The prevention of myxedema coma entails paying
      special attention to certain high-risk patient groups. These groups include older
      women with a history of Hashimoto's thyroiditis, or previous irradiation or
      thyroid surgery for hyperthyroidism. Inform such patients of the symptoms and
      signs of hypothyroidism, and perform annual thyroid function tests, such as a
      serum TSH, in order to provide early, adequate treatment once the test becomes
      positive.

PMID- 1987443
TI  - The problem of the nodular goiter.
AB  - Nodular goiter is a worldwide problem involving millions of persons. Endemic
      goiter, and associated cretinism, is totally preventable by ensuring an adequate
      dietary iodine intake and eliminating malnutrition and dietary goitrogens.
      Therapy, on the other hand, is difficult in that the goiters often do not regress
      and the cretinoid changes are irreversible. Nonendemic goiter due to autoimmune
      thyroid disease, genetic defects in thyroid hormone biosynthesis, and
      environmental goitrogens or neoplasia is not usually preventable. The usual
      therapy, involving TSH suppression by administration of L-thyroxine orally, will
      frequently bring about regression of early, diffuse goiters but is often
      ineffective in bringing about regression of large, multinodular goiters. In these
      patients, surgical removal of the goiter may be necessary for alleviation of
      obstructive symptoms. Further research is needed to elucidate the factors
      involved in the development of these multinodular goiters and to control the
      autocrine and paracrine factors involved in nodule growth.

PMID- 1987444
TI  - Thyroid cancer.
AB  - There have been important recent advances in our understanding of the biologic
      nature of thyroid cancer and in the early diagnosis of the disease. Despite these
      advances, there is still considerable controversy over the management of thyroid
      cancer, including the extent of surgery, the indications for the use of iodine
      131, the effectiveness of thyroid-stimulating hormone suppression, and the
      prediction of outcome. In this review, the current status of the diagnosis and
      management of the various types of thyroid cancer are carefully reviewed and
      extensively documented.

PMID- 1987445
TI  - The effects of nonthyroid disease and drugs on thyroid function tests.
AB  - Serious nonthyroid illness and caloric deprivation, which so often accompany
      systemic illness, have diverse and still incompletely understood effects on
      thyroid hormone economy. We have discussed the pathophysiologic basis for the
      most common pattern of alterations in routine thyroid function tests: a decreased
      serum T3 concentration; normal or, in critically ill patients, a low total serum
      T4 level; and a normal free T4 concentration. Another, less frequent pattern
      (high total and free T4 with a normal serum T3) can be encountered transiently in
      the acutely ill medical or psychiatric patient. With the recent advent of
      sensitive assays for TSH and better methods for serum free T4, it is now possible
      to define more quickly and accurately the thyroid-metabolic status of most of
      these sick patients; the vast majority are euthyroid. Certain drugs confound the
      picture. The most important of these include dopamine and high-dose
      glucocorticoids, both of which suppress TSH secretion from the pituitary and may
      actually cause a state of central hypothyroidism. Other drugs have multiple
      effects on thyroid hormone indices (e.g., amiodarone). Knowledge of all of the
      ways in which systemic illness, starvation, and certain drugs may influence
      thyroid function tests is crucial in assessing the thyroid status of patients
      with serious nonthyroid disease.

PMID- 1987446
TI  - Advances in molecular biology. Potential impact on diagnosis and treatment of
      disorders of the thyroid.
AB  - Advances in molecular biology research continue to have a major impact on
      clinical medicine. These advances have provided a means to produce proteins
      previously available in limited supply and allow for the production of novel
      proteins that are improved agonists or else antagonists with greater specificity
      for therapeutic targets. Newer drug delivery systems should facilitate delivery
      of these proteins. By combining the capabilities to produce drug targets in
      acceptable quantities with improved methods for determining the three-dimensional
      structures of these targets, novel organic therapeutic molecules that act on
      these targets will be designed. Gene transfer therapy using genes that express
      important proteins or that encode "antisense" RNAs that inhibit the translation
      of specific mRNAs will soon become a reality. The use of RFLPs and PCR
      methodologies promises increased means to diagnose specific genetic diseases and
      infections. Most importantly, molecular biology is helping to understand the
      mechanisms of disease such that novel diagnostic and therapeutic approaches can
      be described. These advances are providing an understanding of the mechanisms
      involved in cancers of the thyroid gland. They have already led to an enhanced
      understanding of (1) the growth factors that control proliferation of the thyroid
      gland, (2) the potential steps in thyroid nodule and neoplasia development, (3)
      particular mutations that may occur as thyroid cancers develop, (4) oncogenes
      that are expressed in thyroid cancers, and (5) the genetic defects that are
      responsible for thyroid gland malignancies in the multiple endocrine neoplasia
      (MEN) syndromes. With the latter, the RFLP technology has already provided an
      enhanced means to diagnose the disorder. With further progress, enhanced means
      for diagnosis and treatment should emerge. Molecular biology techniques are
      contributing to an increased understanding of the mechanisms of development of
      autoimmune thyroid disease as with Graves' disease and Hashimoto's thyroiditis.
      The potential role of infections, histocompatibility antigens, thyroid gland and
      extraglandular antigens, immune modulators, subpopulations of T-cells such as
      suppressor and helper cells, other cells involved in immune responses, and a
      combination of influences of several different functions on the thyroid gland are
      being defined. This knowledge should soon suggest improved means for diagnosis
      and treatment. Understanding of the function of the thyroid hormone receptors
      should have clinical importance. This knowledge suggests a means to develop
      thyroid hormone antagonists that may be used to more rapidly ameliorate the
      effects of hyperthyroidism and could be useful in nonthyroidal disorders such as
      cardiac arrhythmias.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1987447
TI  - Thyroiditis. Acute, subacute, and chronic.
AB  - Inflammatory diseases of the thyroid are collectively the commonest thyroid
      disorder. Individually, they range from the rare case of acute bacterial
      thyroiditis to the other end of the spectrum, the even rarer Riedel's
      thyroiditis. Relatively common thyroid inflammatory diseases include the subacute
      thyroiditis syndromes. Of particular interest to endocrinologists is that both
      subacute granulomatous (painful) thyroiditis and subacute lymphocytic (painless)
      thyroiditis are very similar in terms of clinical course, although most likely
      have different etiologies. Nevertheless, their similarities suggest the
      possibility that there may be etiologic heterogeneity for the syndromes. From a
      clinical standpoint, it is essential to differentiate subacute painless
      thyroiditis from Graves' disease, because these two disorders also may mimic each
      other, yet only Graves' disease requires specific therapy. Chronic lymphocytic
      (Hashimoto's) thyroiditis, the commonest of the thyroiditides, presents with
      goiter and either hyperthyroidism (uncommon), hypothyroidism (common), or
      euthyroidism (most common). When L-T4 therapy is used in the treatment of
      Hashimoto's thyroiditis, the physician must be alert to the possibility of excess
      thyroid hormone administration. Sensitive TSH measurements help to avoid this
      therapeutic pitfall.

PMID- 1987448
TI  - Graves' disease. Current concepts.
AB  - Graves' disease is an organ-specific autoimmune disorder. There is no universal
      agreement on the mechanism of Graves' disease, but the over-activity of the
      thyroid is due to an antibody capable of attaching to and activating the TSH
      receptor of follicular cells. There are other extrathyroidal features that are
      not caused either by this antibody or by hyperthyroidism. The clinical diagnosis
      is generally straightforward and can be confirmed by in vitro measurement of
      thyroid hormones and TSH. A measurement of radioiodine uptake is also valuable.
      Treatment is not specific for the immunologic defect, but its purpose is to lower
      the thyroid hormone levels to normal. This can be achieved with antithyroid
      medication, radioiodine iodine-131, or thyroidectomy. In most clinical
      situations, a strong argument can be made for iodine-131 therapy, which is safe
      and definitive, although posttreatment hypothyroidism and the need for lifelong
      thyroxine are to be expected.

PMID- 1987449
TI  - The ophthalmopathy of Graves' disease.
AB  - Fortunately, most patients with thyroid-related eye disease have mild ocular
      involvement that spontaneously involutes. Less than 5% of patients with
      hyperthyroidism will develop sufficiently severe ocular abnormalities that will
      require surgical intervention. Most patients with thyroid eye findings should be
      symptomatically managed. Some will require use of either topical drops or oral
      steroids to alleviate their eye problems. In approximately one half of those
      patients who present acutely with severe thyroid orbital finding, nonsurgical
      therapies will be sufficient to control their eye disease. In the other half,
      eventually multiple surgical procedures may be required, and as discussed
      previously, the timing and sequence of those procedures are crucial to achieve
      optimal results.

PMID- 1987450
TI  - 3'-Phosphoadenosine-5'-phosphosulfate: photoaffinity ligand for sulfotransferase
      enzymes.
AB  - Sulfation is an important pathway in the biotransformation of many drugs,
      xenobiotic compounds, neurotransmitters, and hormones. The sulfate donor for
      these reactions is 3'-phosphoadenosine-5'-phosphosulfate (PAPS). We set out to
      determine whether PAPS might serve as a photoaffinity ligand for sulfotransferase
      enzymes. UV irradiation of [35S]PAPS with partially purified human liver
      thermostable (TS) phenol sulfotransferase (PST) radioactively labeled a protein
      with a molecular mass of 35 kDa, as estimated by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. Photoaffinity labeling of TS PST with [35S]
      PAPS did not require the presence of a phenolic substrate but rather was
      inhibited by p-nitrophenol, a sulfate acceptor substrate for TS PST. Inhibitors
      of TS PST enzymatic activity, including 3'-phosphoadenosine-5'-phosphate, ATP,
      ADP, and 2,6-dichloro-4-nitrophenol, also inhibited photoaffinity labeling of the
      35-kDa protein with [35S]PAPS, in a concentration-dependent fashion, with IC50
      values of 14 microM, 2.1 mM, 7.7 mM, and 91 microM, respectively. The 35-kDa
      protein that was radioactively labeled by [35S]PAPS in the presence of UV light
      coeluted with TS PST enzymatic activity during gel filtration high performance
      liquid chromatography. [35S]PAPS was then used to photoaffinity label another
      sulfotransferase enzyme, the thermolabile (TL) form of PST partially purified
      from human liver. Therefore, [35S]PAPS appears to be a photoaffinity ligand that
      could be used to study a variety of PAPS-dependent sulfotransferases.
      Photoaffinity labeling of TS and TL PST, as well as other PAPS-dependent
      sulfotransferases, should enhance our ability to purify this important group of
      enzymes and to determine amino acid sequences at or near their active sites.

PMID- 1987451
TI  - Immunological evidence for N-acetyltransferase isozymes in the rabbit.
AB  - An immunological evaluation of N-acetyltransferase (NAT) (EC 2.3.1.5) in liver,
      duodenum, lung, and kidney of the rabbit is described. Polyclonal antibodies to
      hepatic NAT isolated from rapid acetylator rabbits were raised in a goat and
      utilized for immunoblot analyses and enzyme inhibition studies. Immunoblot
      analyses demonstrated that hepatic and duodenal cytosols from rapid but not slow
      acetylator rabbits contained an immunoreactive 33-kDa protein. No
      immunoreactivity was observed for lung or kidney cytosols from either rapid or
      slow acetylators. The inhibition of sulfamethazine and p-aminobenzoic acid
      acetylation by polyclonal antibodies was investigated using cytosols from rapid
      and slow acetylator rabbits. With rapid acetylator cytosols, maximal inhibition
      of hepatic, duodenal, and lung NAT activities was 94.4 +/- 9.0%, 92.5 +/- 8.5%,
      and 28.3 +/- 2.4%, respectively, for sulfamethazine (500 mM) acetylation and 90.1
      +/- 8.0%, 80.2 +/- 6.4%, and 26.7 +/- 3.1%, respectively, for p-aminobenzoic acid
      (500 microM) acetylation. Using 25 microM p-aminobenzoic acid as substrate,
      maximal inhibition of NAT activity was 32.0 +/- 2.1% with liver cytosol and 5.8
      +/- 0.16% with duodenal cytosol, whereas no inhibition of lung NAT activity was
      observed. Kidney NAT activity was not inhibited by the polyclonal antibodies.
      With slow acetylator cytosols, no inhibition of NAT activities was observed. It
      is concluded that at least two NATs are present in liver, duodenum, and lung of
      rapid acetylator rabbits. Furthermore, the principal NAT in liver and duodenum is
      immunologically related to the minor form of lung NAT and is antigenically
      distinct from kidney NAT of rapid acetylators. Hepatic, duodenal, lung, and
      kidney NAT(s) of slow acetylator rabbits is (are) immunologically distinct from
      the major hepatic NAT in rapid acetylators. The data support the model in which
      the hepatic polymorphism in rabbits is caused by the total lack of the major
      rapid acetylator hepatic NAT in the phenotypic slow acetylator animal. These
      observations may have significant implications in the organ-specific toxicities
      of carcinogens that undergo metabolic activation via N-acetylation.

PMID- 1987452
TI  - Characterization of the binding of a novel nonxanthine adenosine antagonist
      radioligand, [3H]CGS 15943, to multiple affinity states of the adenosine A1
      receptor in the rat cortex.
AB  - The triazoloquinazoline CGS 15943 is the first reported nonxanthine adenosine
      antagonist that has high affinity for brain adenosine receptors. In the present
      study, the binding of [3H] CGS 15943 to recognition sites in rat cortical
      membranes was characterized. Saturation experiments revealed that [3H]CGS 15943
      labeled a single class of recognition sites with high affinity (Kd = 4 nM) and
      limited capacity (Bmax = 1.5 pmol/mg of protein). Competition studies revealed
      that the binding of [3H]CGS 15943 was consistent with the labeling of brain
      adenosine A1 receptors. Adenosine agonists inhibited 1 nM [3H]CGS 15943 binding
      with the following order of activity N6-cyclopentyladenosine (IC50 = 15 nM)
      greater than 2-chloroadenosine greater than (R)-N6-phenylisopropyladenosine
      greater than 5'-N6-ethylcarboxamidoadenosine greater than (S)N6
      phenylisopropyladenosine greater than CGS 21680 greater than CV 1808 (IC50
      greater than 10,000 nM). The potency order for adenosine antagonists was CGS
      15943 (IC50 = 5 nM) greater than 8-phenyltheophylline greater than 1,3-dipropyl-8
      (4-amino-2-chloro)phenylxanthine greater than 1,3-diethyl-8-phenylxanthine
      greater than theophylline = caffeine (IC50 greater than 10,000 nM). Antagonist
      inhibition curves were steep and best described by a one-site binding model. In
      contrast, adenosine A1 agonist competition curves were shallow, as indicated by
      Hill coefficients less than unity. Computer analysis revealed that these
      inhibition curves were best described by a two-site binding model. Agonist
      competition curves generated in the presence of 1 mM GTP resulted in a rightward
      shift and steepening of the inhibition-concentration curves, whereas antagonist
      binding was not altered in the presence of GTP. The complex binding interactions
      found with adenosine agonists indicate that [3H]CGS 15943 labels both high and
      low affinity components of the adenosine A1 receptor in the rat cortex.
      Additionally, the present data also provide some evidence that [3H]CGS 15943 may
      also recognize an additional low affinity binding component, which may represent
      a putative low affinity A2b receptor in this tissue.

PMID- 1987453
TI  - [3H]cytisine binding to nicotinic cholinergic receptors in brain.
AB  - Cytisine, a ganglionic agonist, competes with high affinity for brain nicotinic
      cholinergic receptors labeled by any of several nicotinic 3H-agonist ligands.
      Here we have examined the binding of [3H]cytisine in rat brain homogenates.
      [3H]Cytisine binds with high affinity (Kd less than 1 nM), and specific binding
      represented 60-90% of total binding at all concentrations examined up to 15 nM.
      The nicotinic cholinergic agonists nicotine, acetylcholine, and carbachol compete
      with high affinity for [3H]cytisine binding sites, whereas among nicotinic
      receptor antagonists only dihydro-beta-erythroidine competes with high affinity
      (in the nanomolar range). Comparison of binding in several brain regions showed
      that [3H]cytisine binding is higher in the thalamus, striatum, and cortex than in
      the hippocampus, cerebellum, or hypothalamus. The pharmacology and brain regional
      distribution of [3H]cytisine binding sites are those predicted for neuronal
      nicotinic receptor agonist recognition sites. The high affinity and low
      nonspecific binding of [3H]cytisine should make it a very useful ligand for
      studying neuronal nicotinic receptors.

PMID- 1987454
TI  - Role of the peripheral anionic site on acetylcholinesterase: inhibition by
      substrates and coumarin derivatives.
AB  - Propidium has been demonstrated in previous studies to be a selective ligand for
      the peripheral anionic site on acetylcholinesterase (EC 3.1.1.7). Its association
      with this site can be advantageously monitored by direct fluorescent titration.
      We have measured the ability of acetylcholine, acetylthiocholine, haloxon [di-(2
      chloroethyl)3-chloro-4-methylcoumarin-7-ylphosphate] , and a coumarin derivative
      (3-chloro-7-hydroxy-4-methylcoumarin) to dissociate propidium from the peripheral
      anionic site of Torpedo californica acetylcholinesterase. Measurements were made
      by back-titration of propidium after complete inhibition of the active center
      with diisopropylfluorophosphate. Both acetylcholine and acetylthiocholine show
      substrate inhibition at high substrate concentrations. The concentrations
      required for occupation of the peripheral site, as ascertained by competition
      with propidium, correlated well with the concentration dependence for the
      kinetics of substrate inhibition. These observations are consistent with
      substrate inhibition being due to binding of acetylcholine or acetylthiocholine
      at a peripheral anionic site. Displacement of propidium by haloxon and coumarin
      indicated that these inhibitors also bind to the peripheral anionic site. The
      dissociation constants ascertained from peripheral site occupation are in
      agreement with the constants obtained from inhibition kinetics. Evidence is
      presented that competition with propidium obtained by direct fluorescence
      titrations, when combined with inhibition kinetics, provides a more reliable
      means for ascertaining site selectivity of various inhibitors than does a kinetic
      analysis alone.

PMID- 1987455
TI  - Status report of the International Programme on Chemical Safety's Collaborative
      Study on plant test systems.

PMID- 1987456
TI  - Pentachlorophenol.
AB  - Pentachlorophenol (PCP) is a substance whose widespread use, mainly in wood
      protection and pulp and paper mills, has led to a substantial environmental
      contamination. This in turn accounts for a significant exposure of the general
      human population, with rather high exposure levels being attained in occupational
      settings. Investigations on the genotoxic activity of PCP have given rise to
      divergent results which would seem to make an evaluation difficult. By grouping
      them into 3 categories a somewhat clearer picture, allowing finally an
      (admittedly tentative) assessment, can be obtained. PCP does seem to be at most a
      weak inducer of DNA damage: it produces neither DNA-strand breaks nor clear
      differential toxicity to bacteria in rec-assays in the absence of metabolic
      activation. Also in SCE induction no increase can be observed in vivo, while PCP
      is found marginally active in a single in vitro experiment. Metabolic activation,
      however, leads to prophage induction and to DNA strand breaks in human
      lymphocytes, presumably through the formation of oxygen radicals. A possible
      further exception in this area might be the positive results in the yeast
      recombination tests, although their inadequate reporting makes a full evaluation
      difficult. PCP does not seem to induce gene (point) mutations, as most bacterial
      assays, the Drosophila sex-linked recessive lethal test and in vitro assays with
      mammalian cells did not demonstrate any effects. Marginally positive results were
      obtained in the mammalian spot test in vivo and in one bacterial test; the
      positive result in the yeast assay for cycloheximide resistance is fraught
      somewhat with its questionable genetic basis. PCP does, however, induce
      chromosomal aberrations in mammalian cells in vitro and in lymphocytes of exposed
      persons in vivo. Those in vivo results that were unable to provide evidence of
      chromosomal damage are hampered either by methodological inadequacies or by too
      low exposure levels. The (rodent) metabolite tetrachlorohydroquinone might be a
      real genotoxic agent, capable of binding to DNA and producing DNA strand breaks;
      this activity is probably due to semiquinone radical formation and partly
      mediated through active oxygen species. Since this compound has not been tested
      in the common bacterial and mammalian mutagenicity assays, the few ancillary
      results on this substance cannot be used in a meaningful human risk assessment of
      PCP. Furthermore, this metabolite has only been produced by human liver
      microsomes in vitro, but has not been detected in exposed humans in
      vivo.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1987457
TI  - International Commission for Protection Against Environmental Mutagens and
      Carcinogens. ICPEMC publication No. 18. Review of the genotoxicity and
      carcinogenicity of antischistosomal drugs; is there a case for a study of
      mutation epidemiology? Report of a task group on mutagenic antischistosomals.
AB  - One of the interests of ICPEMC is to identify situations in which the possible
      induction of inherited defects in man by mutagen exposure could actually be
      studied. The large-scale use of mutagenic drugs in field programmes against
      schistosomiasis, mainly during the 1970's, was considered a possible case. An
      ICPEMC task group approached the problem by (1) updating the genetic toxicology
      data base for antischistosomal drugs, and (2) reviewing possible study areas.
      Expertise was combined from genetic toxicology, mutation epidemiology and
      tropical medicine. It was considered that: (a) if any, hycanthone would be the
      most appropriate candidate drug for study; (b) it would be virtually impossible
      to meet the basic requirements of an appropriate mutation epidemiology study, in
      endemic countries; (c) as more defined genetic endpoints would be selected (e.g.
      sentinel phenotypes) the required large sample sizes would seem prohibitive,
      since documentation on past programmes is limited and local demography would
      render the reliable tracking of substantial numbers of offspring of treated
      persons an almost impossible task; (d) in most endemic countries proper diagnosis
      and registration of inherited defects is largely lacking; (e) the problems
      encountered in demonstrating inherited effects in humans after heavy or chronic
      exposure to established animal mutagens such as ionizing radiation and cancer
      chemotherapy, in combination with the ambiguous nature of the animal germ cell
      data with hycanthone, do not particularly warrant large expectations; (f) since
      non-mutagenic antischistosomal drugs are now in use, the problem is academic and
      of low priority in the endemic countries whose medical and research resources are
      often limited. Thus, studying offspring of hycanthone-treated people to
      demonstrate the mutagenic potential of the drug in man is not a viable
      enterprise.

PMID- 1987458
TI  - The erythrocyte sedimentation rate in congestive heart failure.
AB  - BACKGROUND AND METHODS: Physicians have long believed that the erythrocyte
      sedimentation rate is low in patients with congestive heart failure, but this
      concept is based on a misinterpretation of the results in a single report
      published in 1936. To reevaluate this concept in the modern era, we measured the
      sedimentation rate in 242 patients who were referred for treatment of chronic
      heart failure. RESULTS: The sedimentation rate was low (less than 5 mm per hour)
      in only 24 patients (10 percent) but was increased (above 25 mm per hour) in 50
      percent. Patients with low or normal sedimentation rates (less than or equal to
      25 mm per hour) had more severe hemodynamic abnormalities than patients with
      elevated rates: lower cardiac index (mean +/- SEM, 1.7 +/- 0.1 vs. 2.0 +/- 0.1
      liters per minute per square meter of body-surface area) and higher mean right
      atrial pressure (mean +/- SEM, 12 +/- 1 vs. 9 +/- 1 mm Hg) (both P less than
      0.0001). New York Heart Association functional class IV symptoms were present in
      66 percent of the patients with a low or normal sedimentation rate, as compared
      with 42 percent of those with elevated rates (P less than 0.0001). After one to
      three months of therapy, patients whose sedimentation rates decreased showed
      little hemodynamic or clinical response to treatment, whereas both cardiac
      performance and functional status improved in patients whose rates increased (P
      less than 0.02 for the comparison between groups). The sedimentation rate was
      correlated with the plasma fibrinogen level (r = 0.64, P = 0.0025), and changes
      in the sedimentation rate during treatment were correlated inversely with changes
      in mean right atrial pressure (r = -0.57, P = 0.0002). During long-term follow
      up, patients with low or normal sedimentation rates had a worse one-year survival
      than patients with elevated rates (41 vs. 66 percent, P = 0.01). CONCLUSIONS:
      These data indicate that the erythrocyte sedimentation rate is correlated with
      the severity of illness in patients with chronic heart failure. Because of its
      lack of discriminatory power, however, the test is of limited value in the
      clinical management of this disorder.

PMID- 1987459
TI  - Exposure to an aeroallergen as a possible precipitating factor in respiratory
      arrest in young patients with asthma.
AB  - BACKGROUND: Exposure to airborne spores of the common mold Alternaria alternata
      has been implicated in asthma attacks. Such exposure is particularly frequent in
      the Midwest during the summer and fall months. To determine the role of A.
      alternata in triggering severe asthma attacks, we investigated the cases of 11
      patients with asthma who had sudden respiratory arrest and determined the
      frequency of sensitivity to this allergen in these patients. METHODS: The 11
      patients (age range, 11 to 25 years) with initial episodes of respiratory arrest,
      which was fatal in 2 patients, were identified in the course of their care in our
      pediatric and adult clinical allergy practice and by a retrospective review of
      all Mayo Clinic records of patients with severe asthma cared for between 1980 and
      1989. Skin-test reactivity to A. alternata and levels of IgE antibody against
      this mold in the 11 patients were compared with those in 99 matched controls with
      asthma who had no history of respiratory arrest. RESULTS: All the patients came
      from the upper Midwest, and the episodes of respiratory arrest occurred in the
      summer or early fall. Ten of the 11 patients with asthma who had respiratory
      arrest (91 percent) had positive skin-puncture tests for sensitivity to
      alternaria, as compared with 31 percent of the controls (P less than 0.001), and
      the serum levels of IgE antibodies to alternaria were elevated in all 9 patients
      tested. Among the covariates we examined (age, sex, and distance from the Mayo
      Clinic), only age was a significant confounder. After adjustment for age,
      alternaria skin-test reactivity was found to be associated with an increase of
      approximately 200-fold in the risk of respiratory arrest (adjusted odds ratio,
      189.5; 95 percent confidence interval, 6.5 to 5535.8). CONCLUSIONS: Exposure to
      the aeroallergen A. alternata is a risk factor for respiratory arrest in children
      and young adults with asthma.

PMID- 1987461
TI  - Fluoroquinolone antimicrobial agents.

PMID- 1987460
TI  - Incidence of adverse events and negligence in hospitalized patients. Results of
      the Harvard Medical Practice Study I.
AB  - BACKGROUND: As part of an interdisciplinary study of medical injury and
      malpractice litigation, we estimated the incidence of adverse events, defined as
      injuries caused by medical management, and of the subgroup of such injuries that
      resulted from negligent or substandard care. METHODS: We reviewed 30,121 randomly
      selected records from 51 randomly selected acute care, nonpsychiatric hospitals
      in New York State in 1984. We then developed population estimates of injuries and
      computed rates according to the age and sex of the patients as well as the
      specialties of the physicians. RESULTS: Adverse events occurred in 3.7 percent of
      the hospitalizations (95 percent confidence interval, 3.2 to 4.2), and 27.6
      percent of the adverse events were due to negligence (95 percent confidence
      interval, 22.5 to 32.6). Although 70.5 percent of the adverse events gave rise to
      disability lasting less than six months, 2.6 percent caused permanently disabling
      injuries and 13.6 percent led to death. The percentage of adverse events
      attributable to negligence increased in the categories of more severe injuries
      (Wald test chi 2 = 21.04, P less than 0.0001). Using weighted totals, we
      estimated that among the 2,671,863 patients discharged from New York hospitals in
      1984 there were 98,609 adverse events and 27,179 adverse events involving
      negligence. Rates of adverse events rose with age (P less than 0.0001). The
      percentage of adverse events due to negligence was markedly higher among the
      elderly (P less than 0.01). There were significant differences in rates of
      adverse events among categories of clinical specialties (P less than 0.0001), but
      no differences in the percentage due to negligence. CONCLUSIONS: There is a
      substantial amount of injury to patients from medical management, and many
      injuries are the result of substandard care.

PMID- 1987462
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 6-1991. A 27-year-old woman with Hodgkin's disease and an adrenal
      mass.

PMID- 1987463
TI  - Fatal and near-fatal asthma.

PMID- 1987464
TI  - The long-term effects of exposure to low doses of lead in childhood.

PMID- 1987465
TI  - Corticosteroids in children with corrosive injury of the esophagus.

PMID- 1987466
TI  - Suicidal ideation related to fluoxetine treatment.

PMID- 1987467
TI  - The new technology assessment.

PMID- 1987468
TI  - Uniform requirements for manuscripts submitted to biomedical journals.
      International Committee of Medical Journal Editors.

PMID- 1987470
TI  - Visual perception. Deciphering the colour code.

PMID- 1987469
TI  - Fetal tissue research. New panel for ethical issues.

PMID- 1987471
TI  - Malaria. Variation and vaccination.

PMID- 1987472
TI  - Cell adhesion. Sticky sugars for selectins.

PMID- 1987473
TI  - Still hope for malaria vaccine?

PMID- 1987474
TI  - Mitochondrial proteins essential for viability mediate protein import into yeast
      mitochondria.
AB  - Only five mitochondrial proteins are known to be essential for viability of the
      yeast Saccharomyces cerevisiae; all of them are key components of the
      mitochondrial protein import system. Other components of this system are not
      essential for life; they include functionally redundant import receptors on the
      mitochondrial surface and enzymes acting upon only a few precursor proteins.

PMID- 1987475
TI  - Changes in colour appearance following post-receptoral adaptation.
AB  - Current models of colour vision assume that colour is represented by activity in
      three independent post-receptoral channels: two encoding chromatic information
      and one encoding luminance. An important feature of these models is that
      variations in certain directions in colour space modulate the response of only
      one of the channels. We have tested whether such models can predict how colour
      appearance is altered by adaptation-induced changes in post-receptoral
      sensitivity. In contrast to the changes predicted by three independent channels,
      colour appearance is always distorted away from the direction in colour space to
      which the observer has adapted. This suggests that at the level at which the
      adaptation effects occur, there is no colour direction that invariably isolates
      only a single post-receptoral channel.

PMID- 1987476
TI  - Allele- and haploid-specific product generated by alternative splicing from a
      mouse t complex responder locus candidate.
AB  - Mouse t haplotypes represent a variant form of chromosome 17 that has evolved the
      ability to propagate through natural populations by the phenomenon of
      'transmission ratio distortion' (TRD), in which heterozygous +/t males transmit
      their t-carrying chromosome to 95% or more of their offspring. Although multiple
      t-associated loci have a role in expression of this phenotype, only one--the t
      complex responder (Tcr) locus--is responsible for determining which of the two
      homologues of chromosome 17 will be transmitted at a high ratio. A candidate gene
      (Tcp-10b) for Tcr that is expressed in both meiotic and post-meiotic male germ
      cells has been cloned. But for this candidate gene to function as the haploid
      effector of TRD, the t-allele of this gene (Tcp-10bt) must express a unique
      product in a haploid-specific manner. Here we show that a change in the splicing
      pattern of Tcp-10bt transcripts occurs during sperm differentiation. This change
      results in a unique allele-specific and haploid-specific transcript which could
      encode a variant polypeptide that would fulfil the conditions required of the Tcr
      effector of TRD.

PMID- 1987477
TI  - Progression from lymphoid hyperplasia to high-grade malignant lymphoma in mice
      transgenic for the t(14; 18).
AB  - Follicular lymphoma, the most common human lymphoma, characteristically has a
      t(14; 18) interchromosomal translocation. It is typically an indolent disease
      comprised of small resting B cells, but frequently develops into a high-grade
      lymphoma. The t(14; 18) translocates the Bcl-2 gene, generating a deregulated Bcl
      2-immunoglobulin fusion gene. Bcl-2 is a novel inner mitochondrial membrane
      protein that extends the survival of certain cells by blocking programmed cell
      death. To determine the oncogenic potential of the t(14; 18) translocation, we
      produced transgenic mice bearing a Bcl-2-immunoglobulin minigene that
      structurally mimicked the t(14; 18). An indolent follicular hyperplasia in these
      transgenic mice progressed to a malignant diffuse large-cell lymphoma. The long
      latency, progression from polyclonal to monoclonal disease, and histological
      conversion, are all suggestive of secondary changes. Half of the immunoblastic
      high-grade lymphomas had a rearranged c-myc gene. Our transgenic mice provide an
      animal model for tumour progression in t(14; 18) lymphoma and show that prolonged
      B-cell life increases tumour incidence.

PMID- 1987478
TI  - Erythroid differentiation in chimaeric mice blocked by a targeted mutation in the
      gene for transcription factor GATA-1.
AB  - The zinc-finger transcription factor GATA-1 (previously known as GF-1, NF-E1 or
      Eryf 1 binds to GATA consensus elements in regulatory regions of the alpha- and
      beta-globin gene clusters and other erythroid cell-specific genes. Analysis of
      the effects of mutations in GATA-binding sites in cell culture and in binding
      assays in vitro, as well as transactivation studies with GATA-1 expression
      vectors in heterologous cells, have provided indirect evidence that this factor
      is involved in the activation of globin and other genes during erythroid cell
      maturation. GATA-1 is also expressed in megakaryocytes and mast cells, but not in
      other blood cell lineages or in non-haemopoietic cells. To investigate the role
      of this factor in haematopoiesis in vivo, we disrupted the X-linked GATA-1 gene
      by homologous recombination in a male (XY) murine embryonic stem cell line and
      tested the GATA-1-deficient cells for their ability to contribute to different
      tissues in chimaeric mice. The mutant embryonic stem cells contributed to all non
      haemopoietic tissues tested and to a white blood cell fraction, but failed to
      give rise to mature red blood cells. This demonstrates that GATA-1 is required
      for the normal differentiation of erythroid cells, and that other GATA-binding
      proteins cannot compensate for its absence.

PMID- 1987480
TI  - Genetic engineering. TNF production licensed.

PMID- 1987479
TI  - Chambon among winners of Swiss prize.

PMID- 1987481
TI  - A cleanish bill of health.

PMID- 1987482
TI  - Japan prize winners.

PMID- 1987483
TI  - UK government funds humane research.

PMID- 1987484
TI  - AIDS research. Better late than never for minorities.

PMID- 1987485
TI  - Food irradiation. Compromise eludes EC.

PMID- 1987487
TI  - Fraudulent slur.

PMID- 1987486
TI  - Animal procedures research.

PMID- 1987488
TI  - Gene therapy in perspective.

PMID- 1987489
TI  - Oldest bone disease.

PMID- 1987490
TI  - Man-made antibodies.
AB  - Monoclonal antibodies can now be genetically engineered and endowed with new
      properties. In the future, gene technology could enable antigen-binding fragments
      to be made by exploiting repertoires of variable domain genes derived from
      immunized animals and expressed in bacteria. How readily can this approach be
      extended to production of 'in vitro' repertoires of variable domain genes, and
      obviate the immunization of animals?

PMID- 1987491
TI  - Rejection of class I MHC-deficient haemopoietic cells by irradiated MHC-matched
      mice.
AB  - Irradiated MHC-heterozygous mice often reject bone marrow cells transplanted from
      one of the homozygous parental strains, a phenomenon ('hybrid resistance') that
      appears to violate the laws of transplantation. Rejection of parental and
      allogeneic marrow cells also differs from conventional T cell-mediated rejection
      mechanisms as it is effected by NK1.1+ cells. To account for the unusual
      specificity of bone marrow rejection, it has been proposed that NK1.1+ cells
      destroy marrow cells that fail to express the full complement of self MHC class I
      (MHC-I) molecules. We show here that NK1.1+ cells in normal mice reject
      haemopoietic transplants from mice that are deficient for normal cell-surface MHC
      I expression because of a targeted mutation in the beta 2-microglobulin gene.
      These findings demonstrate that deficient expression of MHC-I molecules renders
      marrow cells susceptible to rejection.

PMID- 1987492
TI  - Gene therapeutics.

PMID- 1987494
TI  - Phase II study of continuous venous infusion of 5-fluorouracil in advanced
      pancreatic cancer.
AB  - Continuous venous infusion of 5-fluorouracil (5FU) was investigated in 18
      patients with measureable advanced cancer of the pancreas. 5FU was given for 7
      days in a dose of 500 mg/m2 by continuous venous infusion over a 24-hour period
      and then followed by a dose of 170 mg/m2 for more than 28 days. Ten patients had
      no change including 1 patient with minor response, and 4 patients had disease
      progression. Serum CA19-9 levels were measured serially after chemotherapy in 13
      of 14 evaluable patients. In 3 of 10 patients who showed high levels before
      treatment, serum CA19-9 levels were significantly decreasing after treatment.

PMID- 1987493
TI  - Immunosuppressive acidic protein and CA 125 levels in patients with ovarian
      cancer.
AB  - The serum levels of immunosuppressive acid protein (IAP) and CA 125 were
      determined in 98 patients with ovarian cancer, in 20 patients with benign ovarian
      tumors and in a group of normal postmenopausal women as controls. On the basis of
      the mean values of normal controls (346.46 +/- 133.26 micrograms/ml), the IAP
      threshold was fixed at 613 micrograms/ml. Increased IAP levels were found in
      70.4% of patients with ovarian cancer, in 25% of benign tumors and in 4.5% of
      normal women. Elevated levels of CA 125 were observed in 66.6% of cancers, in 40%
      of benign tumors and in 6.9% of controls. In particular, in early stage ovarian
      cancer the combined assay of the two markers increased by about 30% with respect
      to CA 125 alone. The simultaneous determination of IAP and CA 125 allowed an
      overall sensitivity of 84% without any significant reduction of specificity.

PMID- 1987495
TI  - Does serum CAR-3 play a role in pancreatic cancer diagnosis?
AB  - A new tumour marker, CAR-3, was isolated using the monoclonal antibody technique
      and measured in the sera of 27 patients with pancreatic cancer, 25 chronic
      pancreatitis, 30 extra-pancreatic diseases and in that of 18 healthy controls in
      order (1) to evaluate the diagnostic role of CAR-3 in patients with pancreatic
      cancer and (2) to ascertain whether liver dysfunction influences CAR-3 serum
      levels. The increased levels were found in 12/27 patients with pancreatic cancer
      (sensitivity 44.4%). No increase was found in patients with chronic pancreatitis,
      whereas abnormal levels were found in patients with other gastrointestinal
      diseases, especially those of the liver and biliary tract. Correlations were
      found between serum CAR-3 and (1) total bilirubin and (2) alkaline phosphatase.
      In conclusion, CAR-3, an antigen structurally related to CA 19-9, does not appear
      to be accurate enough to be considered a tumour marker. Cholestasis seems to
      increase CAR-3 levels as well as those of other glycoproteic tumour markers,
      probably by interfering with the hepatic clearance of these substances.

PMID- 1987496
TI  - Can a patient with neuroblastoma be diagnosed by a single urine sample collected
      randomly?
AB  - We have observed that a fairly large amount of vanillylmandelic acid and
      homovanillic acid in urine samples taken randomly from patients with a tumor of
      about 10 g was less than the cutoff values and overlapped with the respective
      ranges of normal infants. Consequently, with only a single random urine sample
      there is a risk of overlooking a patient, especially in cases where the tumor is
      small. However, according to theoretical calculation, several random urine
      samples may enable us to discriminate a patient from a normal infant and can
      replace the 24-hour urine accumulation for 3 days which is currently performed
      for final judgement in the mass screening of neuroblastoma.

PMID- 1987498
TI  - Suicide risk among incident cases of cancer in the Swiss Canton of Vaud.
AB  - Data collected by the Cancer Registry of the Canton of Vaud, Switzerland, wer
      used to estimate the risk of suicide for patients diagnosed with cancer. Among
      24,166 cases of invasive neoplasms other than nonmelanomatous skin cancer
      reported between 1976 and 1987 and followed through integrated active follow-up
      to the end of 1987, for a total of 57,164 person years at risk, there were 55
      registered suicides vs. 21.3 expected (standardized mortality ratio, SMR = 2.6;
      95% confidence interval, Cl = 2.0-3.4). The ratio was slightly, but not
      significantly higher for males (SMR = 2.8) than for females (SMR = 2.2) and
      comparable across subsequent age groups. The risk of suicide was high during the
      1st year after notification (SMR = 3.9) and decreased to 2.2 between 1 and 5
      years and to 1.5 over 5 years. This study suggests that the risk of suicide after
      a diagnosis of cancer may be greater than previously estimated from cancer
      registry data in Finland, Sweden, and Connecticut (USA), at least in this
      population of Central Europe with high overall suicide rates.

PMID- 1987497
TI  - DNA flow cytometry in the prognosis of primary malignant melanoma.
AB  - DNA flow cytometry was carried out on 804 primary melanomas. The data were
      analyzed with a follow-up of 24-96 months. 57% of the cases were diploid, 32% had
      one abnormal cell population, and 11% were multiclonal. In 8% of the aneuploid
      tumors there were cell lines in the hypertetraploid range. A reliable S phase
      determination was possible in 524 cases. Among these 11% had an S phase exceeding
      15%. Using an increased tumor thickness, relapse rate and mortality as criteria
      of tumor progression, aneuploidy and multiclonality, the occurrence of
      hypertetraploid cell lines and a high S phase (greater than 15%) proved to be
      correlated with a poor prognosis.

PMID- 1987499
TI  - Diffuse well differentiated lymphocytic lymphoma: a clinical study of 22
      patients.
AB  - An analysis is presented of the clinical and prognostic features of 22 patients
      diagnosed with diffuse well differentiated lymphocytic lymphoma at Cleveland
      Metropolitan General Hospital between 1974 and 1987. At presentation, the disease
      was usually advanced with 86% of patients having stage IV disease and 73% of
      patients exhibiting bone marrow involvement. Ten second malignancies were
      documented in 7 (32%) of our patients. The goal of treatment in our patients was
      palliation except in the 2 stage 1 patients. The response rate to initial
      treatment was 55% (15% complete), although 75% of patients ultimately responded
      to some form of therapy; and the mean survival was 58 months, a figure not
      different from historical controls. There were no differences in survival between
      patients given simple versus complex therapy at diagnosis or at any time during
      the course of their disease; and no differences in survival between complete,
      partial and nonresponders.

PMID- 1987500
TI  - Immunologic and immunohistochemical studies on chronic lymphocytic thyroiditis
      with or without thyroid lymphoma.
AB  - The local immunologic phenomena in the thyroid gland of 16 patients with chronic
      lymphocytic thyroiditis (CLTH) were investigated; 5 of these cases were
      associated with thyroid non-Hodgkin's lymphomas (NHL). All patients were admitted
      because of struma, growing slowly in patients with CLTH alone and rapidly in
      those with associated thyroid NHL. CLTH was confirmed by histologic findings,
      including the presence of lymphoid follicles or thyroid autoantibodies in the
      serum in all 16 patients. Immunologic study revealed that all thyroid NHL were of
      the B cell type. Surface maker study of suspended cells showed that the
      percentages of E-rosette-forming cells in patient with CLTH and thyroid NHL (38.0
      +/- 10.0%) and in patients with CLTH alone (45.0 +/- 11.9%) were between those of
      B cell NHL of lymph node and B cell hyperplasia reported by others.
      Immunohistochemical studies confirmed the reactive nature of lymphoid follicles.
      Subset distribution of T and B lymphocytes in patients with CLTH and thyroid NHL
      markedly contrasted with that in patients with CLTH alone: an increased ration of
      CD8+ cells (suppressor/cytotoxic cell) to CD4+ cells (helper/inducer cell). There
      was a marked increase in the number of immunosuppressive acidic-protein(IAP)
      containing macrophages in the thyroid lesion and serum IAP level in patients with
      thyroid NHL. These findings provide evidence of a difference in the local
      immunologic conditions in CLTH alone compared to CLTH complicated by thyroid NHL.

PMID- 1987501
TI  - Chemotherapy (CAP) for the treatment of advanced ovarian cancer and second-effort
      surgery in the second look.
AB  - Seventy-two patients with advanced ovarian cancer received CAP chemotherapy
      followed by laparotomy and 'second-effort' surgery. The overall response to CAP
      therapy was 80%. A complete pathological response (CPR) was obtained in 16
      patients and partial microscopic (PMiR) and macroscopic responses in 7 and 33
      cases, respectively. The actuarial survival for the entire group was 36% at 50
      months with a median survival of 34 months. No significant differences in
      survival between the CPR and PMiR groups were found. Radical second-effort
      surgery showed a somewhat beneficial effect. The tumor size before chemotherapy
      (less than 5 cm) and FIGO stage III had a significantly favorable effect on
      response rate and survival.

PMID- 1987502
TI  - The response of mouse tumours to fractionated doses of pions: determination of
      therapeutic gain factor.
AB  - Using the same experimental system which had been used to determine the pion
      relative biological effectiveness (RBE) for skin of mouse foot by Chaplin et al.,
      we have determined the pion RBE for KHT sarcoma and SCCVII tumour transplanted in
      the foot of C3H mice. The pion RBE obtained by the tumour growth delay time
      method in comparison with 250 kVp X-rays at a dose rate of 150 cGy per min was
      determined to be 1.20, 1.28 and 1.50 with single, 4 and 10 fractions,
      respectively, for KHT sarcoma. As for SCCVII tumour, it was determined to be
      1.17, 1.45 and 2.05 with single, 4 and 10 fractions respectively. Therefore, it
      has been concluded that pions have various values of RBE depending on the tumour
      system involved. KHT sarcoma is a tumour which grows very rapidly, on the
      contrary, SCCVII tumour shows somewhat slower growth characteristics. These
      differences of RBE between these two tumour systems possibly stem from
      differences in the amount of hypoxic cells and/or their rates of reoxygenation.
      As for therapeutic gain factor, a maximum value of 1.45 was obtained with 10
      fractions using the SCCVII tumour. Pions seem to be most effective (in multiple
      fractions) against tumours of relatively slow growth.

PMID- 1987503
TI  - [Continuous breast stimulation in prenatal fetal diagnosis].
AB  - Fifty, high risk pregnancies were studied, where not more than 7 days before
      labour passed, an unilateral continuous breast stimulation test was performed.
      The predictive value, the testing time and the side effects of the method were
      analyzed. According to the results this breast stimulation test reliably
      indicates the fetal state. The testing time of the endogenous oxytocin challenge
      test is shorter than that of the exogen oxytocin challenge test. Because of the
      risk of hyperstimulation the test must be performed with intensive maternal and
      fetal observation. In the opinion of the authors the breast stimulation test-
      because of its reliability, shorter testing time and simpleness--should be the
      first choice among the challenge tests and only in case of a failure comes an
      exogen oxytocin challenge test into question.

PMID- 1987504
TI  - [Percutaneous transhepatic cholecysto-lithotripsy].
AB  - Authors were the first in Hungary to perform the percutaneous transhepatic
      cholecystolithotripsy for the removing of gallbladder stones. The method can be
      performed easily with the necessary skill and it is not too troublesome for the
      patients. They present their beginning experience.

PMID- 1987505
TI  - [The use of an isolated jejunum segment in gastric surgery].
AB  - The author summarizes the possibilities of the employment of isolated jejunum
      segment in gastric surgery. After a short historical review, the author tries to
      indicate the site of the surgical method in the treatment of gastroduodenal
      peptic ulcers, corrosive internal injuries of the stomach and gastric cancers,
      and surgical correction of the operated stomach. In gastric surgery today,
      besides the use of the "traditional" Billroth-type resections, vagotomies, and
      the Roux-type surgical methods, gastric resection performed with jejunum
      interposition has practically sank into oblivion. However, with the
      implementation of selective surgical principles this method can stand its place
      in gastrointestinal surgery. With proper judgement of its employment, the
      attained level of success could probably be improved.

PMID- 1987506
TI  - [Malignant B-cell lymphoma in a patient with primary Sjogren syndrome].
AB  - Authors report the case of a 42 years old female with primary Sjogren's syndrome
      in whom nine years after the beginning of her disease generalised swollen
      lymphatic nodes and enlargement of liver as well as a spleen has appeared. The
      simultaneous appearance of fever, loss of body weight and worsening of her
      general condition raised the possibility of an associated malignant
      lymphoproliferate disease. The histology of a lymph node proved the presence of a
      highly malignant form of B-cell lymphoma (CB NHL). Attention is drawn to the
      necessitate of regular control of patients with Sjogren's syndrome.
      Lymphadenopathy, the decrease of the immunoglobulin levels and autoantibody titer
      in the serum, as well as the predominance of monoclonal immunoglobulins point to
      the possibility of malignant transformation. With reference to the presented case
      a short review of the Sjogren's syndrome is given by the authors.

PMID- 1987508
TI  - [ A case of successfully treated duodenal hemangioma].
AB  - In some cases the radical removal of gastrointestinal hemangiomas involves an
      excessive risk or too extensive operation. Consequently some other solution has
      to be applied. At our patient with duodenum haemangioma the combination of
      angiographic embolism and endoscopic sclerotization was successfully employed.

PMID- 1987507
TI  - [Clinical observations on breast cancer in males].
AB  - The analysis of clinical parameters of seventeen male breast cancer patients
      clearly demonstrate the correlation between prognosis and size of primary tumour
      as well as regional spread. The localization of the tumour in the breast is not
      correlated to survival. Intelligent hormonal therapy contributes to improving of
      survival. Detections of plasma FSH, LH, testosterone, 17 beta estradiol levels
      are useful in examining of pathomechanism, revealing relapse, and monitoring
      hormonal therapy.

PMID- 1987509
TI  - [Trichophagia treated successfully by intravenous iron injections].
AB  - The case of a trichophagic child is presented. Oral and intramuscular iron
      therapy brought only temporary effect at the age of 3. Seven years later the 10
      year-old highly intelligent girl ate again hair. She was not anaemic and her
      serum iron level was not low. Intravenous iron injections applied again ceased
      immediately the psychic aberration that did not return even after 4 years. The
      authors are of the opinion that in cases of such psychic anomalies the iron
      content of the iron-rich cerebral ganglia is lower than normal and the
      disturbance can be ceased by the administration of iron.

PMID- 1987510
TI  - [Heterogeneity of surface antigens in chronic B-cell lymphoid leukemia].
AB  - Clinical and immunological studies of fifty patients with CLL have been
      performed. No correlation was found either between the clinical stage or clinical
      course of the disease and the distribution of cell surface makers characteristic
      of CLL (CD19, CD20, CD21, HLA-DR, sIg). Therapy did not influence the
      distribution of B lymphocyte subpopulations. On the other hand we recognized
      differences when examining the B-cell specific features. The CD21 antigen was
      present in significantly lower proportion when compared to all other B-cell
      markers. This suggests the presence of immature B-cell population. Correlation
      studies showed a strong correlation between the presence of the CD5 antigen and
      the antigens CD19, CD20, HLA-DR and sIg, while a similar correlation could not be
      proved between the CD5 antigen and CD21 marker. Thus the application of the CD5
      antibody together with any of the B-cell markers seems to be sufficient for the
      diagnostics of CLL with the exception of the CD21 antibody that marks only a
      small proportion of the B-cell population in CLL, so it can be used for purposes
      of clinical diagnostics.

PMID- 1987511
TI  - Epidemiology of pediatric HIV infection.
AB  - Perinatal transmission of human immunodeficiency virus (HIV) continues to
      increase. In 1989 alone, it is estimated that 1750 infected children were born in
      the United States. Although transmission is spreading to areas outside the cities
      originally most affected, these cities continue to bear the greatest toll.
      Adolescents may be particularly vulnerable to HIV infection; education and
      counseling are critical for controlling the epidemic in this age group.

PMID- 1987512
TI  - Childhood AIDS.

PMID- 1987513
TI  - AIDS in the transfusion recipient.
AB  - In summary, the HIV virus was transmitted to approximately 90% of recipients by
      infectious blood and blood products transfused prior to donor and product testing
      begun in March 1985. Self-elimination of at-risk donors several years prior to
      testing donor blood helped to reduce the number of infected donations. Virtually
      all contaminated donors are now eliminated. The multiply transfused patient
      developed a stimulated dysregulated immune system due to the numerous antigens
      and the iron in red cells and plasma. This dysregulated immune system has
      resulted in a variable response to the added exposure of the HIV virus. The
      incubation period and progression to disease have been prolonged and variable.
      Although a small number of patients have progressed as rapidly as other at-risk
      groups, many continue to do well without therapeutic intervention. Natural
      history of the disease needs continual monitoring to determine the ultimate
      outcome of these transfusion recipients.

PMID- 1987514
TI  - Antiviral therapy for human immunodeficiency virus infection in children.
AB  - Antiretroviral therapy for children is still at an early stage, although progress
      is being made slowly. Zidovudine administered at 180 mg/m2/dose every 6 hours is
      the current standard therapy for symptomatic children and those with low CD4
      counts. This standard is likely to evolve as further testing clarifies the
      optimal dosage for ZDV in different populations. Children on ZDV need to be
      monitored very closely (at least monthly) for hematologic side effects, which are
      most common in the more seriously ill children. The role of some of the newer
      antiretrovirals, like ddI and ddC, which are likely to be licensed, has yet to be
      established. They have a different toxicity profile than ZDV and thus may work
      well in combination with it. The issue of peripheral neuropathy and the lack of
      an easy test to measure it makes using ddC or ddI in young, preverbal children a
      daunting proposition. As with ZDV, the optimum dosage and timing have yet to be
      fixed for ddC or ddI alone, and even less available are regimens for combination
      therapy. Antiretroviral drugs other than the dideoxynucleosides are less well
      developed. Some, like high-titer antiviral immunoglobulin, involve technology
      that is already available and thus will be relatively easy to study. Others, like
      the antisense oligomers, are such a new technology that there are many hurdles to
      be overcome as the agents move from the laboratory to the clinic. The goal of
      agents that work on sites other than reverse transcriptase is a reasonable one,
      but the work in perfecting such new categories of drug is difficult and slow. In
      the meantime, children with HIV should be symptomatically supported and offered
      the most effective antiretroviral regimens available.

PMID- 1987515
TI  - Pediatric HIV disease. The newest chronic illness of childhood.
AB  - HIV disease has emerged as a major chronic illness of childhood. Children with
      HIV infection and children with other chronic health impairments have much in
      common, including the need for comprehensive, multidisciplinary, coordinated care
      that includes special attention to the psychosocial effects on the child and
      family. However, because the mother and often the father and siblings share this
      lethal viral infection, the impact of HIV disease upon the family surpasses that
      of virtually all other chronic conditions. This is compounded by the association
      of the disease with drug use, its preponderance among the most disenfranchised
      populations in the United States, and the persistent public fear and
      discrimination surrounding AIDS. We have made substantial progress already in the
      medical management of this infection, and while we await the development of more
      effective therapies, we already have the tools and knowledge in hand to help
      these families.

PMID- 1987516
TI  - Laboratory diagnosis of HIV infection.
AB  - Laboratory diagnosis of human immunodeficiency virus (HIV) infection is
      complicated by absence of data on sensitivity, specificity and predictive value
      of the various tests as they apply to children. The presence of maternal anti-HIV
      passively transmitted across the placenta also confounds diagnosis. The authors
      review currently available data on the detection of HIV, HIV genome, and HIV gene
      products, as well as the diagnostic value of detecting serologic and cellular
      responses to HIV in infants and children.

PMID- 1987517
TI  - Host defense abnormalities associated with HIV infection.
AB  - Infection with human immunodeficiency virus (HIV) impairs immune function. Most
      abnormalities in host defense associated with HIV infection are due to helper T
      cell dysfunction. Studies defining these abnormalities in the HIV-infected
      patient have largely been done in adults. A more complete understanding of the
      immunodeficiency that occurs in infants and young children congenitally infected
      with HIV awaits further study of their immune function and the effect this virus
      has on the developing immune system.

PMID- 1987518
TI  - Medical care of the HIV-infected child.
AB  - Familiarity with the demographics of pediatric HIV disease and recognition of
      common and uncommon presentations of infection are keys to diagnosing the HIV
      infected child. Subsequent management entails preventative care, including
      immunizations and nutritional support, as well as management of HIV-related
      complications.

PMID- 1987519
TI  - Pneumocystis carinii infections in HIV-infected children.
AB  - Since 1981, 1200 children with acquired immunodeficiency syndrome have been
      reported to the Centers for Disease Control. Among these children, Pneumocystis
      carinii has been the leading cause of serious morbidity and mortality. This
      review discusses the epidemiology, diagnosis, and treatment of P. carinii.

PMID- 1987520
TI  - Lymphocytic interstitial pneumonia.
AB  - Lymphocytic interstitial pneumonia is at present a pathologic diagnosis. In the
      setting of a chronic interstitial pneumonia in a child with lymphocytosis,
      hyperglobulinemia, and lymphadenopathy or parotid enlargement, the diagnosis is
      often clinically presumed. At present the diagnosis can be established firmly
      only by lung biopsy. Models of pathogenesis include nonspecific stimulation of
      the immune system, HIV-specific stimulation, or synergy between EBV and HIV.
      Treatment includes oxygen and bronchodilators as needed. The role of zidovudine
      and of steroids in the management of LIP remains to be determined.

PMID- 1987521
TI  - Pathology of childhood AIDS.
AB  - Pathologic lesions in children with acquired immunodeficiency syndrome (AIDS) can
      be classified into three broad categories: (1) primary lesions related directly
      to infection by human immunodeficiency virus (HIV) (e.g., in the lymphoreticular
      system and brain); (2) associated lesions related to direct or indirect sequelae
      of HIV infection (e.g., opportunistic infections, lymphoid interstitial
      pneumonitis, and so forth); and (3) lesions of undetermined pathogenesis (e.g.,
      cardiomyopathy, nephropathy, and so forth). The pathologic features of the
      various lesions in these three categories are described. Clinical relevance of
      the pathologic study of AIDS is discussed. Data on perinatal pathology of AIDS is
      reviewed.

PMID- 1987522
TI  - Upper respiratory tract infections in young children: duration of and frequency
      of complications.
AB  - This study was performed to determine the usual duration of community-acquired
      viral upper respiratory tract infections and the incidence of complications
      (otitis media/sinusitis) of these respiratory tract infections in infancy and
      early childhood. Children in various forms of child-care arrangements (home care,
      group care, and day care) were enrolled at birth and observed for 3 years.
      Families were telephoned every 2 weeks to record on a standardized form the type
      and severity of illnesses experienced during the previous interval. Only children
      remaining in their original child-care group for the entire study period were
      compared. The mean duration of an upper respiratory tract infection varied
      between 6.6 days (for 1- to 2-year-old children in home care) and 8.9 days (for
      children younger than 1 year in day care). The percentage of apparently simple
      upper respiratory tract infections that lasted more than 15 days ranged from 6.5%
      (for 1- to 3-year-old children in home care) to 13.1% (for 2- to 3-year-old
      children in day care). Children in day care were more likely than children in
      home care to have protracted respiratory symptoms. Of 2741 respiratory tract
      infections recorded for the 3-year period, 801 (29.2%) were complicated by otitis
      media. During the first 2 years of life, children in any type of day care were
      more likely than children in home care to have otitis media as a complication of
      upper respiratory tract infection. In year 3, the risk of otitis media was
      similar in all types of child care.

PMID- 1987523
TI  - Professional liability in a pediatric emergency department.
AB  - The risk of professional liability resulting from care given in the pediatric
      emergency department is a growing concern. This retrospective study examined the
      patients, diagnoses, and outcome of all threatened and actual claims that
      originated in the emergency department of a pediatric teaching hospital from 1977
      through 1988. Twenty-five cases were identified by the hospital risk manager from
      approximately 320,000 visits (8.0 cases/100,000 visits); 22 charts were available
      for review. Ages of the patients ranged from 2 weeks to 13 years (mean 2.9 years,
      median 3.0 years). The patients' payment status was private insurance (n = 10),
      state public aid (n = 5), and no third-party payment source was listed for 7
      children. Ten patients (46%) visited the emergency department between midnight
      and 8:00 AM, when an attending physician was not present. Return visits within 2
      weeks for the same complaint occurred in 10 cases. The majority of the patients
      were discharged home (n = 18), and all of them had appropriate, adequately
      documented discharge instructions. The final diagnoses fell into four general
      categories: minor trauma/abuse (n = 7), neoplasms/chronic illnesses (n = 7),
      infectious diseases (n = 6), and appendicitis (n = 2). Review of the charts
      before knowledge of the legal outcome raised quality-of-care issues in 41% of the
      cases (n = 9).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1987524
TI  - Diagnostic utility of lower extremity radiographs of young children with gait
      disturbance.
AB  - The diagnostic utility of lower extremity radiographs was evaluated using 84
      outpatients 1 to 5 years of age with gait disturbance whose lower extremities
      appeared physically normal. Chief complaints included limp (65 children [77%]),
      refusal to walk or stand (37 children [44%]), and frequent falling (6 children
      [7%]). A total of 43 children (51%) had more than one complaint. The mean age of
      patients was 26 months and the median duration of symptoms was 1 day. Trauma was
      reported in 43 (51%) cases and fever in 14 (17%). Results of radiographical
      studies appeared normal in 81 children (96%), demonstrated soft tissue swelling
      in 2 children, and revealed a bony island in 1 child. In 1 patient admitted to
      the hospital for failure to thrive and irritability, and whose radiographic
      results appeared normal, findings consistent with osteomyelitis later developed.
      Of the remaining children, 68 (81%) were available for follow-up observation 4 to
      28 months after the initial visit and all reported spontaneous resolution of the
      initial complaint. It was concluded that in a well-appearing child with an
      otherwise normal physical examination results, an acute gait disturbance is
      likely to be a self-limiting condition and radiographs are unlikely to contribute
      to the diagnosis.

PMID- 1987525
TI  - Premature sexual activity as an indicator of psychosocial risk.
AB  - Although unprotected premature sexual activity is associated with well-defined
      biologic risks of sexually transmitted disease and pregnancy, the concomitant
      psychosocial risks are less well documented. The strength of association (odds
      ratio) of coital status with other risk behaviors and feelings was examined in
      1504 junior high school students. Among the 12 through 16-year-old students, 63%
      of the boys and 36% of the girls were nonvirginal (had had intercourse at least
      once). The proportion of sexually experienced boys and girls increased with age.
      Nonvirginal boys and girls were significantly (P less than .001) more likely than
      their virginal cohorts to engage in other activities considered risky. The odds
      ratios for nonvirginal youth ranged from 3.5 for girls having used drugs other
      than alcohol or marijuana, to 10.4 for girls having used marijuana. Nonvirginal
      boys and girls were also at significantly greater risk for engaging in minor
      delinquent acts and having school problems. Nonvirginal girls (but not boys) were
      6.3 times more likely to report having attempted suicide. The strength of
      associations with feelings was weaker. Nonvirginal girls were at slightly greater
      risk for reporting feeling lonely, feeling upset, and having difficulty sleeping.
      A significant proportion of the students reported sexual experience and ever use
      of alcohol or marijuana (45% of boys, 27% of girls). There were strong age
      effects so that by age 15 years, 63% of the boys and 50% of the girls reported
      experience with both activities. The data suggest that early sexual experience
      among adolescents is associated with other potentially health-endangering
      behaviors and that the syndrome of problem behaviors is important in this age
      group.

PMID- 1987526
TI  - Elevated plasma aluminum levels in normal infants receiving antacids containing
      aluminum.
AB  - Aluminum toxicity is a documented cause of encephalopathy, anemia, and
      osteomalacia. Excretion is primarily renal; therefore, patients with renal
      insufficiency are at risk for aluminum accumulation and toxicity. This has been
      demonstrated in uremic children treated with aluminum-containing antacids. The
      purpose of this study was to determine whether plasma aluminum levels were
      elevated in infants with normal renal function during prolonged aluminum
      containing antacid use. Ten study infants (mean age = 5.8 months), who had been
      receiving antacids for at least 1 week, were compared with 16 control infants
      (mean age = 9.8 months) not receiving antacids. The study patients consumed 123
      +/- 16 mg/kg per day (mean +/- SEM) of elemental aluminum for an average of 4.7
      weeks. Their plasma aluminum level (37.2 +/- 7.13 micrograms/L) was significantly
      greater than that of the control group (4.13 +/- 0.66 micrograms/L) (P less than
      .005). It is concluded that plasma aluminum levels may become elevated in infants
      with normal renal function who are consuming high doses of aluminum-containing
      antacids. The safety of antacids containing aluminum should not be assumed and
      they should be used judiciously in infants, with careful monitoring of the
      aluminum dose and plasma level.

PMID- 1987527
TI  - Individual differences in children's response to pain: role of temperament and
      parental characteristics.
AB  - Sixty-five families were enlisted in a study exploring factors associated with
      distress behavior in 5-year-old children receiving diphtheria-tetanus-pertussis
      immunizations. At a home visit 1 month before the immunization, the following
      measures were obtained: (1) the Behavioral Style Questionnaire, a measure of
      temperament: (2) parental self-reports of medically related attributes (eg. "good
      patient"); (3) parental attitudes toward pain in children and responsiveness to
      their child's pain; and (4) parental prediction of distress at upcoming
      immunization. The child's distress behavior during the immunization was evaluated
      using a modification of the Procedure Rating Scale-Revised and, after the
      procedure, the child's assessment of his or her pain was elicited using the
      Oucher. Children's mean Procedure Rating Scale-Revised score was 2.57 of a
      possible 11. Thirty-one (48%) had low (less than or equal to 1) and 7 (11%) had
      high distress scores (greater than or equal to 2 SD above the mean). Factors
      positively correlated with distressed behavior included more "difficult child"
      cluster characteristics, the individual temperamental dimension of adaptability,
      but few parental attitudes and attributes. Parent's predictions of distress were
      the strongest correlates. These findings document the variation that children
      demonstrate in response to pain and offer some insight into associated innate and
      environmental factors. These results imply that treatment strategies derived from
      parental knowledge and tailored to individual characteristics of the child may be
      most effective in alleviating pain-related distress in medical settings.

PMID- 1987528
TI  - Factors associated with delay in diagnosis of childhood amblyopia.
AB  - The prevention of permanent visual impairment from amblyopia is an important goal
      of pediatric vision screening. Unfortunately, many cases of amblyopia are not
      diagnosed until the child is too old to benefit maximally from treatment. A
      review of patient records from the practice of a private pediatric
      ophthalmologist confirmed that late detection is a frequent occurrence among
      children with amblyopia who have had good access to health care. A case-control
      study was then used to identify factors associated with delayed diagnosis, in
      which children with an adverse outcome (diagnosed at or after 5 years of age)
      were compared with those with an optimal outcome (diagnosed before 5 years of
      age). The chart review identified 161 children with amblyopia who participated in
      this study; 75 had late diagnoses (case patients) and 86 served as control
      patients. Children with early diagnoses more often had the following
      characteristics: a positive family history of strabismus, greater degrees of
      strabismus (when strabismus was present), higher maternal educational level,
      greater parental suspicion that an eye problem existed, and an increased chance
      that the parents requested the eye examination that led to the diagnosis. The
      parents of children with late diagnoses expressed less concern over the
      seriousness of amblyopia but were more likely to report that their children had
      suffered adverse consequences of amblyopia. When diagnosed early, amblyopia was
      more often detected by the child's primary health care provider. Physicians of
      the children with early diagnoses more often reported compliance with both the
      American Academy of Pediatrics guidelines for vision screening in infancy and
      referral for vision problems.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1987529
TI  - Methsuximide for intractable childhood seizures.
AB  - Methsuximide was added to the therapeutic regimens of 25 children with
      intractable epilepsy. In 15 patients the drug was well tolerated and resulted in
      a 50% or greater reduction in seizure frequency. No serious or irreversible
      adverse effects were seen. Methsuximide is frequently overlooked and may be an
      effective adjunctive antiepileptic for children with intractable seizures.

PMID- 1987530
TI  - Sudden infant death syndrome and small airway occlusion: facts and a hypothesis.
AB  - Respiratory failure is almost certainly the cause of death in the majority of
      cases of sudden infant death syndrome (SIDS), but the mechanisms leading to it
      have not been elucidated. SIDS shares many environmental and socioeconomic risk
      factors with severe forms of bronchiolitis, and the age distribution of incident
      cases is similar. Present knowledge of lung and airway development during
      infancy, determinants of peripheral airway patency, changes in lung surface
      activity in infants with SIDS, and fluid film dynamics in small airways are
      reviewed. It is hypothesized that many cases of SIDS may be due to a final
      episode of progressive peripheral bronchial occlusion in infants with preceding
      critically diminished conductance of the smaller airways.

PMID- 1987532
TI  - Changing immunization referral patterns among pediatricians and family practice
      physicians, Dallas County, Texas, 1988.
AB  - Family practice physicians and pediatricians in Dallas County, Texas, were
      surveyed to determine how recent vaccine price increases have changed
      immunization referral patterns. A total of 73% of responding physicians referred
      some pediatric patients for immunization in 1988. Public health clinics were the
      largest referral source with more responding pediatricians (84.4%) referring
      patients than did responding family practitioners (66.5%). Referrals to the
      clinics were most often made when patients were unable to afford immunizations in
      a private practice setting. Between 1979 and 1988, the number of responding
      pediatricians and family practitioners making immunization referrals increased by
      193% and 391%, respectively. The percentages of children referred for
      immunization increased by 693% during the same decade. It was suggested by our
      survey of Dallas County physicians that a new influx of patients are using public
      sector immunizations, potentially creating additional financial stress for public
      health programs. In addition, this shift to the public sector may undermine the
      health departments' ability to provide new vaccines or protect greater numbers of
      children with immunization.

PMID- 1987531
TI  - Ehrlichiosis in children.
AB  - Tick-borne rickettsiae of the genus Ehrlichia have recently been recognized as a
      cause of human illness in the United States. In the years 1986-1988, 10 cases of
      ehrlichiosis were diagnosed in children in Oklahoma. Fever and headache were
      universal: myalgias, nausea, vomiting, and anorexia were also common. Rash was
      observed in six patients but was a prominent finding in only one. Leukopenia,
      lymphopenia, and thrombocytopenia were common laboratory abnormalities. Six
      patients were treated with tetracycline, three with chloramphenicol, and one was
      not treated with antibiotics: all recovered. The onset of illness in spring and
      early summer for most cases paralleled the time when Amblyomma americanum and
      Dermacentor variabilis are most active, suggesting that one or both ticks may be
      vectors of human ehrlichiosis in Oklahoma.

PMID- 1987533
TI  - Allergenicity of orally administered immunoglobulin preparations in food-allergic
      children.
AB  - Passive immunization by the oral administration of immunoglobulin preparations
      derived from bovine milk, chicken egg, and human sera has been proposed as a
      method for the prevention and treatment of enteric diseases. However, the
      allergenic potential of these proteins may be a factor limiting their widespread
      use for disease prevention. An in vitro study with sera from milk- and egg
      allergic children was performed to determine whether these immunoglobulin
      preparations have allergenic potential. Protein extracts of milk, bovine
      immunoglobulin, egg white, human immune globulin, and five egg yolk antiviral
      immunoglobulin preparations were bound to nitrocellulose paper. These
      preparations were probed for specific IgE binding with sera from milk- and egg
      allergic patients. Of 22 milk-hypersensitive patients, 16 had specific IgE
      binding against the bovine immunoglobulin preparation. Of 28 egg-allergic
      patients 15 had specific IgE binding against one or more of the egg yolk-derived
      antiviral chicken immunoglobulins. Control sera were negative against the milk
      and egg preparations. Western blot analysis confirmed that milk- and egg-allergic
      patients had IgE-specific antibodies for bovine and chicken immunoglobulin
      molecules. Therefore, the removal of contaminating proteins from milk and egg
      antibody preparations would be unlikely to eliminate their allergenic potential.
      In contrast, sera from milk- and egg-allergic patients displayed no detectable
      IgE binding to human immunoglobulin preparations. These data indicate that the
      administration of antibody preparations derived from bovine and chicken sources
      may lead to severe allergic reactions in milk- or egg-sensitized patients and to
      sensitization in some nonallergic individuals.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1987534
TI  - Sucrose as an analgesic for newborn infants.
AB  - The effectiveness of sucrose as an analgesic agent for newborn infants was
      assessed during two standard painful hospital procedures: blood collection via
      heel lance and circumcision. Infants who drank 2 mL of a 12% sucrose solution
      prior to blood collection cried 50% less during the blood collection procedure
      than did control infants who had received 2 mL of sterile water. Crying of
      infants who ingested sucrose returned to baseline levels within 30 to 60 seconds
      after blood collection whereas control infants required 2.5 to 3.0 minutes to
      return to baseline. Like findings were obtained for infants who received sucrose
      on a pacifier prior to and during circumcision. Specifically, control infants who
      underwent a standard circumcision procedure without intervention cried 67% of the
      time. A water-moistened pacifier reduced crying to 49% (P less than .01). Crying
      was reduced further to 31% (P less than .05) by providing infants with a sucrose
      flavored pacifier to suck. These findings, which parallel results obtained in
      studies of pain in infant rats, provide a potent yet simple, benign intervention
      to help alleviate stress and pain routinely experienced by human infants.

PMID- 1987535
TI  - Low-level lead exposure and children's cognitive function in the preschool years.
AB  - In a cohort of 170 middle and upper-middle class children participating in a
      prospective study of child development and low-level lead exposure, higher blood
      lead levels at age 24 months were associated with lower scores at age 57 months
      on the McCarthy Scales of Children's Abilities. The mean blood lead level at age
      24 months was 6.8 micrograms/dL (SD = 6.3; 75th, 90th, and 99th percentiles: 8.8,
      13.7, 23.6, respectively) and for all but 1 child was less than 25 micrograms/dL,
      the current definition of an "elevated" level. After adjustment for confounding,
      scores on the General Cognitive Index decreased approximately 3 points (SE = 1.4)
      for each natural log unit increase in 24-month blood lead level. The inverse
      association between lead level and performance was especially prominent for
      visual-spatial and visual-motor integration skills. Higher prenatal exposures
      were not associated with lower scores at 57 months except in the subgroup of
      children with "high" concurrent blood lead levels (ie, greater than or equal to
      10 micrograms/dL). The concentration of lead in the dentine of shed deciduous
      teeth was not significantly associated with children's performance after
      adjustment for confounding.

PMID- 1987536
TI  - Detection of phenylketonuria in the very early newborn blood specimen.
AB  - Early hospital discharge of newborns is leading to collection of the newborn
      screening blood specimen during the first day of life in increasing numbers of
      newborns. There is concern that neonates with phenylketonuria who are tested this
      early may be missed. To examine this question, the authors screened specimens
      collected during the first 24 hours of life from 23 neonates at risk for
      hyperphenylalaninemia. The blood phenylalanine level in each of the 6 neonates
      with phenylketonuria and a seventh with mild hyperphenylalaninemia was greater
      than 2 mg/dL as early as 4 hours of age and 6 mg/dL or greater by 24 hours of
      age. A newborn screening phenylalanine cutoff level of 2 mg/dL would have
      identified all of these neonates within the first 24 hours of life, but a cutoff
      level of 4 mg/dL would have missed 2 of the 6 with phenylketonuria before 24
      hours of life. Newborn screening programs should adopt a blood phenylalanine
      level of 2 mg/dL as the cutoff for suspicion of phenylketonuria and request for a
      second specimen. Breast-fed affected neonates had higher early blood
      phenylalanine elevations than formula-fed neonates, perhaps reflecting the higher
      protein (phenylalanine) content of colostrum.

PMID- 1987537
TI  - Risks of alternate-day prednisone in patients with cystic fibrosis.

PMID- 1987538
TI  - Graft versus host disease after blood transfusions in a premature infant.

PMID- 1987540
TI  - American Academy of Pediatrics Committee on Child Abuse and Neglect: Guidelines
      for the evaluation of sexual abuse of children.

PMID- 1987539
TI  - Acute myocarditis simulating myocardial infarction in a child.
AB  - Pediatric chest pain usually occurs in benign conditions. However, this case
      portrays the dramatic electrocardiographic appearance of acute myocardial
      ischemia in a boy with biopsy-proven myocarditis who had only mild chest pain.
      This underscores the need for eliciting a detailed history when evaluating a
      patient with chest pain. If the pain cannot be clearly attributed to chest wall
      phenomena, or if there are historical or physical findings suggestive of an
      arrhythmia or angina, then further investigation with a chest radiograph and a 12
      lead electrocardiogram is recommended. Myocarditis must be considered in the
      differential diagnosis of any child whose electrocardiogram is indistinguishable
      from an acute myocardial infarction. Finally, endomyocardial biopsy allows early
      diagnosis and institution of therapy, which may have beneficial effect on
      decreasing morbidity and mortality. Further follow-up and research is still
      needed to evaluate the effect of early treatment of myocarditis on long-term
      myocardial function and the development of chronic cardiomyopathy.

PMID- 1987541
TI  - American Academy of Pediatrics. Committee on Child Abuse and Neglect: Public
      disclosure of private information about victims of abuse.

PMID- 1987543
TI  - American Academy of Pediatrics. Federation of Pediatric Organizations: Statement
      on pediatric fellowship training.

PMID- 1987542
TI  - American Academy of Pediatrics. Section on Radiology: Diagnostic imaging of child
      abuse.

PMID- 1987544
TI  - Use of decubitus position for finding the "olive" of pyloric stenosis.

PMID- 1987545
TI  - Phenytoin (Dilantin) prescribing practices among Long Island, NY pediatricians.

PMID- 1987546
TI  - Race, culture, and ethnicity.

PMID- 1987547
TI  - Aseptic meningitis in the decennium of Borrelia burgdorferi infection (Lyme
      disease)

PMID- 1987548
TI  - Encopresis caused by mother's stoma.

PMID- 1987549
TI  - Comparative analysis of three instruments designed to measure self-care agency.
AB  - A number of instruments are used to measure Orem's (1985) concept of self-care
      agency. Their use reflects basic assumptions that both the instrument and the
      underlying tenets of the theory are valid. The purpose of this study was to
      examine the latent traits associated with three instruments designed to measure
      self-care agency. These included Denyes' (1980) Self-Care Agency, Kearney and
      Fleischer's (1979) Exercise of Self-Care Agency, and Hanson and Bickel's (1985)
      Perception of Self-Care Agency. The convenience sample consisted of 513 adult,
      nonhospitalized subjects who completed the three instruments. Common factor
      analysis and canonical correlation were used to identify latent traits and their
      relationships. The findings support the multidimensionality of Orem's (1985)
      concept of self-care agency. However, the use of one instrument does not
      adequately reflect this multidimensionality.

PMID- 1987550
TI  - The reliability of magnitude estimation for dyspnea measurement.
AB  - The reliability of magnitude estimation with an open scale was evaluated in a
      physiologically stable population of adults with chronic respiratory disease who
      experienced chronic dyspnea. Magnitude estimation was used to measure one
      dimension of dyspnea, perceptual sensitivity. The relationship between external
      inspiratory resistive loads (stimuli) and numbers that reflected the perceived
      intensity of the breathing effort (response) as expressed by a power function was
      measured on three visits 3 to 5 days apart. The correlations of the exponent of
      the power function between visits were high and stable.

PMID- 1987552
TI  - Circadian rhythms in blood pressure in school-age children of normotensive and
      hypertensive parents.
AB  - The purpose of this study was to describe the characteristics of blood pressure
      rhythms in school-age children and to compare the circadian mesors and amplitudes
      between children of normotensive parents and children of hypertensive parents.
      The sample consisted of 40 healthy children between 8 and 10 years old; 20
      children had a parental history of hypertension and 20 did not. Blood pressure
      was measured every 2 hours during the day and every 90 minutes during the night
      for one 24-hour cycle using a Dinamap monitor equipped with an automatic printer.
      Cosinor analyses revealed statistically significant circadian rhythms for
      systolic and diastolic blood pressures in 12 of the 40 subjects. The acrophases
      for systolic and diastolic pressures occurred between 1200-1800 hours. The mean
      systolic mesor was 108.50 while the mean diastolic mesor was 61.41. The mean
      amplitudes were 8.85 for systolic pressure and 7.44 for diastolic pressure. No
      statistically significant differences in circadian mesors and amplitudes between
      children of normotensive parents and children of hypertensive parents were found.

PMID- 1987551
TI  - GI symptoms, function, and psychophysiological arousal in dysmenorrheic women.
AB  - In a previous study, gastrointestinal (GI) symptoms and stool characteristics
      were found to be influenced by menstrual cycle phase. The current study was
      designed to replicate initial work regarding GI symptoms and stool
      characteristics and to explore the relationships between GI symptoms, stool
      characteristics, ovarian hormone levels, and indicators of psychophysiological
      arousal. Fifty women (dysmenorrheic, N = 22; nondysmenorrheic, N = 28) maintained
      a daily dairy for recording stool characteristics, GI symptoms, and daily anxiety
      level. First morning void urine specimens for catecholamine assays and serum
      samples for ovarian hormone and cortisol determinations were obtained at menses,
      follicular, and luteal phases. Results showed menstrual cycle-related differences
      in stool characteristics and report of GI symptoms, with the greatest changes
      occurring at menses in the total sample. Dysmenorrheic women reported higher
      levels of all GI symptoms at menses as compared to nondysmenorrheic women. In
      addition, cycle-related differences in serum cortisol, urine catecholamines, and
      report of anxiety were also noted, particularly in dysmenorrheic women. However,
      looser stools and GI symptoms at menses were not correlated with absolute levels
      of ovarian hormones or indicators of psychophysiological arousal.

PMID- 1987553
TI  - Premature rupture of the membranes and sepsis in preterm neonates.
AB  - This investigation was designed as a historical cohort study using data
      abstracted from medical records. Five hundred seven preterm neonates (26-35 weeks
      gestation) born alive from singleton pregnancies complicated by premature rupture
      of the membranes (PROM) were selected. Each neonate was matched on gestational
      age, gender, ethnicity, and date of delivery to a neonate without PROM. A matched
      pairs analysis was done using risk ratios (RR) to measure strength of the
      association and risk differences (RD) to measure absolute effect. Analysis
      revealed that preterm births complicated by PROM were at significantly higher
      risk of neonatal sepsis (RR = 3.5) and infection (RR = 2.4). The RDs indicated
      that PROM exposure contributed an excess of 5 cases of sepsis per 100 infants (RD
      = 0.05). PROM was not significantly associated with neonatal mortality, but when
      PROM had existed over 48 hours there was a higher risk of sepsis and infection.
      Birth of a neonate over 1500 grams or 33 weeks gestation was the most important
      factor in reducing risk of infection in PROM deliveries.

PMID- 1987554
TI  - A construction report.

PMID- 1987555
TI  - Factors influencing the coping effort of mothers of hospitalized children.
AB  - The purpose of this study was to test a theoretical model predicting the
      relationships among four concepts: predictability of events, control, anxiety,
      and coping effort of mothers of children hospitalized with acute physical
      conditions. The sample consisted of 45 mothers of acutely ill, hospitalized
      children from 1-24 months of age. For each of the concepts, 16 events commonly
      associated with hospitalization of a child were proportionately ranked using
      magnitude estimation measurement technique. The psychometric properties of the
      instrument were estimated through reliability assessment and cross modality
      matching. Multiple regression analysis indicated that 97% of the dependent
      variable, coping effort, was explained by two of the three predictor variables-
      predictability of events and anxiety. Mothers who knew what events to expect
      experienced less anxiety and reported expending less effort to cope with the
      stressful events. Control was not a significant factor in predicting the mothers'
      coping effort.

PMID- 1987556
TI  - Construct and empirical validity of the Self-As-Carer Inventory.
AB  - The Self-As-Carer Inventory was designed to permit individuals to express their
      perceived capacity to care for self. In the first phase of the study, a 44-item
      questionnaire was developed and tested through factor analysis primarily using a
      college population (Geden & Taylor, 1988). After the instrument was revised, a
      second study, reported here, was conducted with a more heterogeneous population.
      The age range of the respondents was broadened and the variability of health
      state and ethnicity was increased. Factor analysis with rotation was conducted on
      589 completed inventories using the revised 40-item questionnaire. The 4-factor
      Promax solution accounted for 52% of the variance. Retention of factors with
      eigenvalues greater than 1 led to a 6-factor solution accounting for 58% of the
      variance. Significant positive correlations were found between total scores on
      the Self-As-Carer Inventory and ratings of health in general (r = .29, p =
      .0001), health at this moment (r = .25, p = .0001), and an estimate; of the
      amount of their own self-care provided (r = .36, p = .0001). No differences were
      found in total scores across health state, defined as respondents' reports of
      being sick-at-home (n = 130), hospitalized (n = 259), or well (n = 200).

PMID- 1987557
TI  - Self-transcendence and mental health in oldest-old adults.
AB  - Patterns of self-transcendence that older adults report as being important to
      their emotional well-being are described in this study, and the relationship
      between self-transcendence and mental health symptomatology in oldest-old adults
      is investigated. The sample consisted of 55 independent-living older adults, 80
      to 97 years old. Methodological trianglulation was used whereby qualitative data
      together with quantitative findings were examined. Four patterns of self
      transcendence, congruent with the investigator's definition, were identified by
      the participants as being important to their sense of well-being: Generativity,
      Introjectivity, Temporal Integration, and Body-Transcendence. Results of Pearson
      correlation analysis and matrix analysis of data supported a relationship between
      self-transcendence and mental health found in previous research, thus
      demonstrating the importance of the expansion of self boundaries in older adults.

PMID- 1987558
TI  - Psychometric and descriptive perspectives of illness impact over the life span.
AB  - This article describes the development of an instrument that quantifies illness
      over the course of life. The sample was comprised of 308 women, aged 50 to 70,
      who were alumnae of a master's program in nursing. Each submitted information
      concerning illness experienced during each decade of life. Each time period was
      then rated multidimensionally (Duration, Discomfort, Interference, Threat to
      Life) to reflect the impact of the various conditions and the means by decade
      (Decade Impact) were computed. In general, after the first two decades, magnitude
      of ratings increased with age, indicating greater disease impact. Interrater
      reliability and internal consistency reliability of the scale were high. Evidence
      for construct validity included substantial differences between those with and
      without specific illness conditions, as well as correlations with hospitalization
      history and health self-ratings. In cluster analysis of patterns across decades,
      five distinct patterns emerged into which subjects were grouped.

PMID- 1987559
TI  - Planning sample sizes: comparison of factor level means.

PMID- 1987561
TI  - Contract nursing 1890.

PMID- 1987560
TI  - Use of health diaries with children.

PMID- 1987562
TI  - Who wants to be a doctor?

PMID- 1987563
TI  - Green issues, Pink courage and blacklists.

PMID- 1987564
TI  - Sitting on the fence.

PMID- 1987565
TI  - Shaping the board.

PMID- 1987566
TI  - Management. A crisis of leadership?

PMID- 1987567
TI  - Leadership. On a fast track to the top.

PMID- 1987568
TI  - Leadership. Promoting potential.

PMID- 1987569
TI  - The ABC of AIDS counselling.

PMID- 1987570
TI  - A sense of the past.

PMID- 1987571
TI  - Making sense of ... intraosseous infusion.

PMID- 1987572
TI  - Ethics. Where are the whistle-blowers?

PMID- 1987574
TI  - Nurse education. How to organise ... induction programmes.

PMID- 1987573
TI  - Nurse education. Impossible dream.

PMID- 1987576
TI  - Child health. Lighting the darkness.

PMID- 1987575
TI  - Child health. Sweet challenge.

PMID- 1987577
TI  - Child health. Reducing fear in hospital.

PMID- 1987578
TI  - Concepts of citrate production and secretion by prostate. 1. Metabolic
      relationships.
AB  - Accumulation and secretion of extraordinarily high levels of citrate are
      principal functions of the prostate gland of humans and other animals. To achieve
      this, prostate secretory cells must possess unique metabolic relationships which
      distinguish them from virtually all other cells. Furthermore, citrate metabolism
      is markedly altered in benign prostatic hyperplasia (BPH) and in prostatic
      carcinoma (CA). This review assimilates existing information and presents current
      concepts related to 1) the pathway of metabolism associated with net citrate
      production, 2) the involvement of transporting mechanisms associated with citrate
      secretion, 3) energy implications of citrate production, 4) altered metabolic
      relationships in BPH and CA, and 5) the importance of citrate relationships as
      biochemical markers for characterizing prostate secretory epithelial cells. It is
      hoped that this review will bring attention to the importance and urgency of
      elucidating and understanding the metabolic relationships associated with citrate
      production by normal and neoplastic prostate epithelial cells. Research in these
      areas has been severely neglected despite the fact that the combined incidence of
      BPH and CA constitutes the most prevalent neoplastic disease among men.

PMID- 1987580
TI  - Secretion of inhibin-like material by rat ventral prostate epithelial cells in
      culture.
AB  - Monolayer cultures of epithelial as well as stromal components of the rat ventral
      prostate were established, taking advantage of differences in the requirement of
      sera supplementation and also in the temporal span for attachment. These
      monolayers were characterized and used to identify the cellular source of
      prostatic inhibin. The spent medium obtained from epithelial cell monolayer alone
      had significant inhibin-like activity.

PMID- 1987579
TI  - Effect of dimethylsulfoxide on the proliferation and glycosaminoglycan synthesis
      of rat prostate adenocarcinoma cells (PAIII) in vitro: isolation and
      characterization of DMSO-resistant cells.
AB  - Dimethylsulfoxide (DMSO) modulates the tumorigenicity and other characteristics
      of some malignant cell lines in vitro. We have investigated DMSO effects on cell
      proliferation and glycosaminoglycan (GAG) synthesis in rat prostate
      adenocarcinoma (PAIII) cells in culture. DMSO inhibited cell proliferation and
      GAG synthesis and shedding. Cells that survived the initial exposure to 2.5% DMSO
      could be propagated in this concentration of the agent and were designated PAIII
      DMSO resistant (PAIII-DMSOr). PAIII-DMSOr cells showed reversible indications of
      increased differentiation such as decreased growth rate and saturation density.
      Although the PAIII-DMSOr cells were grown in 2.5% DMSO, they had normal or
      elevated GAG content. The major GAG of both PAIII and PAIII-DMSOr cells was
      undersulfated heparan sulfate. Verapamil, a calcium channel blocker that reverses
      drug resistance in tumor cells, stimulated the growth of PAIII-DMSOr cells in the
      presence of 2.5% DMSO, but was inhibitory in the absence of DMSO. Growth of PAIII
      cells was inhibited by the differentiating agents sodium butyrate and retinoic
      acid and by the ionophore monensin. Interestingly, growth of PAIII-DMSOr cells in
      the presence of 2.5% DMSO was largely unaffected by sodium butyrate or retinoic
      acid. The results suggest that (1) PAIII-DMSOr cells arise from the induction of
      a compensation mechanism to DMSO effects in a preexisting population of cells:
      (2) there is a correlation between GAG synthesis and cell proliferation; and (3)
      further study of the verapamil effect may help elucidate the mechanism of the
      DMSO-induced differentiation of cancer cells.

PMID- 1987581
TI  - Influence of age, strain, and the testes on rat prostate hormone sensitivity.
AB  - There are conflicting reports in the literature regarding the response of the rat
      prostate to various androgen/estrogen combinations. The reason for these
      conflicting results has been unclear. The purpose of the present study was to
      assess factors that may determine the effect of sex hormones on rat prostate
      growth. The results of this study demonstrate that the prostates of Lewis rats
      respond differently to sex hormone combinations than do those of Sprague Dawley
      rats. Young rats have a different prostate hormone responsiveness than do old
      rats. The presence or absence of the testes alters the responsiveness of the
      prostate gland to androgen-estrogen combinations. These results suggest that
      strain, age, and the presence of the testes are important factors which will
      influence the response of the rat prostate to hormonal manipulation. The
      importance of these factors should be considered in the design of experiments
      which deal with the response of the rat prostate to hormone manipulation.

PMID- 1987582
TI  - Gastrointestinal radiology from the time of Walter B. Cannon to the 21st century.
AB  - From its very inception, gastrointestinal radiology was at the forefront of
      radiology, combining physiologic and anatomic information. From evaluation of
      esophageal motility to the first depiction of gastric ulcers and carcinomas of
      the alimentary tube, gastrointestinal radiology became indispensable to
      physicians and surgeons. Improvements in fluoroscopic and radiographic equipment,
      the tilting table, the image intensifier with the television train, the
      introduction of selective visceral angiography with safer contrast media and,
      more recently, digital subtraction angiography, digital ultrasound (US), color
      Doppler US, computed tomography, and magnetic resonance (MR) imaging--all of
      these advances have made imaging diagnosis more precise and specific. A new
      modality--localized tissue MR spectroscopy--should offer an insight into
      metabolism and suggest optimal modes of treatment and follow-up. The
      gastrointestinal radiologist of the future will have to be multimodality trained.
      A new generation of alimentary tract interventional radiologists will further the
      trend toward less invasive surgical therapy. No end of advances is in sight.

PMID- 1987583
TI  - Carotid sonography.

PMID- 1987584
TI  - The non-Hodgkin lymphomas: practical concepts for the diagnostic radiologist.

PMID- 1987585
TI  - Clinical utility of laser recanalization in occluded peripheral arteries.

PMID- 1987586
TI  - Upper gastrointestinal tract evaluation with radionuclides in infants.

PMID- 1987587
TI  - Matchmaking and McNemar in the comparison of diagnostic modalities.
AB  - Comparative studies of radiologic techniques commonly yield matched data due to
      the ease and desirability of performing all of the techniques on each of the
      patients. The two-by-two matched data array and the McNemar analysis provide a
      succinct format for the presentation and proper analysis of matched comparisons
      of binary (positive and negative) test results. When comparing tests, it is
      essential not to rely on just the statistical significance of the differences in
      sensitivities (or specificities); the magnitude of the differences must also be
      assessed. Confidence intervals provide a useful form of estimation by providing a
      range of plausible values and an indication of the precision of the estimate. The
      matched data array also indicates the complementarity of the diagnostic tests
      being compared.

PMID- 1987588
TI  - Laser angioplasty: results of a prospective, multicenter study at 3-year follow
      up.
AB  - A prospective multicenter trial was initiated to evaluate the efficacy and safety
      of laser angioplasty. Laser recanalization was performed in 338 patients with
      arteriosclerotic femoropopliteal artery occlusions (average length, 8.5 cm).
      Neodymium-yttrium-aluminum-garnet lasers were used in combination with sapphire
      probe catheters. The initial recanalization rate was 85%. Complications were
      observed in 14% of the patients. Emergency surgery was required in 1.5%. The
      cumulative long-term patency rate of the successfully recanalized arteries was
      80%, 70%, 62%, and 57% at 6 months, 1 year, and 2 and 3 years, respectively. The
      patency rates were not affected by the length of the occlusion and the long-term
      medication (platelet inhibition vs anticoagulation), but patients with a normal
      runoff had significantly better patency rates than those with reduced runoff (63%
      vs 52%, P less than .01). The study has shown that laser-assisted angioplasty is
      safe and at least as effective as conventional angioplasty.

PMID- 1987589
TI  - Benign biliary strictures: treatment with percutaneous cholangioplasty.
AB  - Results of percutaneous balloon cholangioplasty of 17 patients with 28 benign
      biliary strictures were compared with those of published radiologic and surgical
      series to determine whether stricture location was related to therapeutic success
      and whether a patient should undergo percutaneous or surgical therapy. Treatment
      was considered successful if there was no anatomic evidence of recurrent
      stricture or need for surgery (mean follow-up, 32 months). Treatment was
      successful in all nine (100%) intrahepatic (zone 1) strictures, 11 of 12 (92%)
      extrahepatic-extrapancreatic (zone 2) strictures, one of three (33%)
      intrapancreatic (zone 3) strictures, and three of four (75%) bilienteric
      anastomotic (zone 4) strictures. Restenosis occurred in five patients;
      cholangioplasty was ultimately successful in two of those patients after
      redilation and stent placement. On the basis of these results and those of
      published radiologic and surgical series, the authors believe that
      cholangioplasty is the treatment of choice for zone 1 strictures and is as
      effective as surgery for zone 2 and 4 strictures. Patients with zone 2 and 4
      strictures with concomitant portal hypertension or a history of multiple previous
      biliary surgical procedures should be considered good candidates for
      cholangioplasty. Zone 3 strictures may be better treated surgically than
      percutaneously.

PMID- 1987590
TI  - Lung abscess: CT-guided drainage.
AB  - Lung abscesses were drained by means of catheters guided by computed tomography
      (CT) in 19 patients who still had sepsis despite standard medical therapy; all
      patients had received antibiotics for at least 5 days, and 11 of the 19 patients
      had undergone bronchoscopy. The abscess was cured (by clinical and radiographic
      criteria) in all 19 patients (100%), and surgery was avoided in 16 of the 19
      patients (84%). Three patients underwent surgery for removal of organized tissue
      or decortication after the lung abscess was evacuated. Complications included a
      hemothorax that required a chest tube in one patient and three minor
      complications (a clogged catheter in two patients and transient elevation of
      intracerebral pressure in one patient). The hemothorax occurred in one of two
      patients in whom the catheter traversed normal lung. The percutaneous drainage
      catheters traversed juxtaposed abnormal pleura on route to the abscess in 17 of
      the patients. CT-guided drainage of lung abscess is an effective method to treat
      lung abscesses that are refractory to conventional therapy; the procedure should
      obviate major operation in most patients. A catheter route through abscess
      pleural syndesis is preferable, and CT is useful for planning this route.

PMID- 1987591
TI  - Delayed rupture of a pseudoaneurysm of the costocervical trunk: treatment with
      therapeutic embolization.
AB  - Fourteen days after removal of an internal jugular catheter inserted prior to
      renal transplantation, a patient presented with brisk arterial hemorrhage from
      the insertion site. The hemorrhage, caused by a ruptured pseudoaneurysm of the
      costocervical trunk, was controlled by transcatheter embolization with gelatin
      particles. One year later the patient reported no problems related to the
      pseudoaneurysm or its management.

PMID- 1987592
TI  - Cineangiography of the heart in a single breath hold with a segmented turboFLASH
      sequence.
AB  - Six healthy volunteers and three patients with cardiac anomalies were studied in
      a comparison of segmented turboFLASH (fast low-angle shot) cine, a method of
      magnetic resonance imaging that permits an entire series of high-resolution cine
      images to be obtained in one breath hold, with standard cine. Segmented
      turboFLASH uses a gradient-echo sequence designed for short imaging times in
      combination with a segmented data acquisition method. Presaturation pulses were
      applied to eliminate the blood pool signal; the signal-to-noise ratio was
      assessed with a phantom. Standard hardware and image reconstruction methods were
      used. The breath-hold images consistently showed reduced ghosting and blurring
      from respiration. Because a very short echo time was used, segmented turboFLASH
      was relatively insensitive to dephasing caused by local field disturbances or
      flow. The authors conclude that, by reducing imaging times and eliminating
      respiratory artifact, segmented turboFLASH can be useful for performing cine
      studies of the heart and great vessels.

PMID- 1987593
TI  - Fatal reactions to intravenous nonionic contrast material.
AB  - Three cases of fatality related to the use of low-osmolality contrast material
      (LOCM) are presented. LOCM definitely reduces unpleasant side effects and serious
      reactions, but data are currently insufficient to determine whether the death
      rate is any different from that associated with high-osmolality contrast agents.
      If the present trend toward universal conversion to LOCM continues, an enormous
      cost for little, if any, lifesaving benefit may be incurred.

PMID- 1987595
TI  - Small sac size in the first trimester: a predictor of poor fetal outcome.
AB  - A nonbradycardiac fetal heart rate is associated with a low rate of spontaneous
      abortion (2%-4%). To determine criteria for predicting impending first-trimester
      loss when a normal fetal heart rate is identified sonographically, the authors
      studied 16 consecutively examined patients with pregnancies of 5.5-9 weeks
      gestation, a small sac size, and fetuses with normal cardiac activity. Mean sac
      size (MSS) was determined and a small sac was diagnosed when the difference
      between the MSS and crown-rump length (MSS--CR) was less than 5 mm. Fifty-two
      consecutively examined patients with pregnancies of 5.5-9 weeks gestation, normal
      sac size, and fetuses with normal heart rate formed the control group. An MSS--CR
      of 5 mm or greater was considered normal. Fifteen of the 16 patients (94%) with
      first-trimester small sacs had spontaneous abortions despite normal sonographic
      cardiac activity. Four of the 52 control patients (8%) with normal sac sizes had
      spontaneous abortions. The authors' data show that, despite the presence of fetal
      cardiac activity at the time of sonography, the usual reassurance provided to
      patients should be guarded when the sac size is small.

PMID- 1987594
TI  - Prediction of severe adverse reactions to ionic and nonionic contrast media in
      Japan: evaluation of pretesting. A report from the Japanese Committee on the
      Safety of Contrast Media.
AB  - In a nationwide prospective study of adverse reactions to intravenous contrast
      media (CM), the Japanese Committee on the Safety of Contrast Media compared high
      osmolar ionic CM with low-osmolar nonionic CM. A total of 337,647 cases were
      analyzed. The reliability of pretesting with an intravenous injection of a small
      amount of CM as a means of predicting severe or fatal reactions was also
      evaluated. The predictive values of the pretest were 1.2% for ionic and 0.0% for
      nonionic CM, and the sensitivity values were 3.7% and 0.0%, respectively. Such
      low values render this test meaningless for predicting which patients are at risk
      of a severe adverse reaction. A comparison of the incidence of severe adverse
      reactions between the nonpretested and pretested patients, as well as between the
      nonpretested and pretested patients with negative results, disclosed no
      statistically significant differences. Also, no beneficial effects of
      premedication in patients with a positive pretest were proved. The authors
      therefore conclude that pretesting with an intravenous injection of a small
      amount of CM is not useful in predicting severe reactions to ionic or nonionic
      CM.

PMID- 1987596
TI  - Gastric emptying in infants and children: limited utility of 1-hour measurement.
AB  - Gastric emptying measurements were performed in infants and children at 1 and 2
      hours after a liquid feeding. The 1-hour measurements were predictive of only 58%
      of the variability in the 2-hour measurements, indicating that the 1-hour
      measurement was not a good predictor of the 2-hour measurement. Gastric emptying
      measurements in children should be continued until 2 hours after feeding unless
      rapid emptying is observed during the 1st hour of the study.

PMID- 1987597
TI  - Simple renal cysts in children: diagnosis and follow-up with US.
AB  - To assess the sonographic frequency of simple renal cysts in children, the
      authors retrospectively reviewed the results of abdominal sonographic studies of
      16,102 children performed over a 5-year period between January 1, 1985, and
      December 31, 1989. Patients with abnormal renal function, dysplastic kidneys, or
      a family history of polycystic kidney disease were excluded from the study. The
      authors' review of the sonograms revealed 37 simple cysts in 35 patients (0.22%);
      the cysts were evenly distributed by age and sex and measured from 0.3 to 7.0 cm
      in maximum diameter. Sixteen cysts (43%) were in the upper pole of the right
      kidney. Follow-up sonographic studies of 23 cysts in 22 patients for up to 5
      years showed no change in size in 17 cysts (74%). The largest cyst was drained
      percutaneously; all other cysts were managed conservatively. No patient showed
      deterioration of renal function. Therefore, the authors concluded that in a
      pediatric patient demonstrating normal renal function, no further intervention is
      necessary when a simple renal cyst is identified at sonography.

PMID- 1987598
TI  - Increased radiation dose at mammography due to prolonged exposure, delayed
      processing, and increased film darkening.
AB  - Four single-emulsion films introduced over the past 2 years--Du Pont Microvision,
      Fuji MiMa, Konica CM, and Eastman Kodak OM--were compared with Eastman Kodak OM
      SO-177 (Min-RE) film to evaluate their varying effects on mean glandular dose of
      reciprocity law failure due to prolonged exposure, delayed processing, and
      increased film darkening as a result of increased radiation exposure to improve
      penetration of glandular tissue. Exposures over 1.3 seconds led to increased
      radiation doses of 20%-30%. Delays in processing of 6 hours decreased processing
      speed by 11%-32% for all films except Du Pont Microvision. Optical density
      increases of 0.40 required 20%-30% more skin exposure for all five films. Optimal
      viewing densities were also evaluated and found to be different for each of the
      five films. Mammographers need to be aware of these differences in mammographic
      films to achieve maximum contrast at mammography.

PMID- 1987599
TI  - Accurate automatic exposure controller for mammography: design and performance.
AB  - An automatic exposure controller has been designed that controls the optical film
      density for film, screen, and radiographic techniques typically used in
      mammography to within 0.05 over a range of 1.3-6.7-cm thickness of Lucite. This
      degree of accuracy is better than that reported for presently available
      controllers. The detector system consists of four cadmium telluride detectors and
      involves the use of a control algorithm to read the detectors and turn off the
      mammography unit at the correct time. This algorithm is implemented by a
      microprocessor, which also provides the means for a convenient calibration.

PMID- 1987600
TI  - Gallstone lithotripsy: relevant physical principles and technical issues.
AB  - A basic understanding of shock wave generation is essential for the radiologist
      who performs gallstone lithotripsy. Shock waves differ from ordinary acoustic
      waves in that they have a rapid rise time, a positive pressure component that
      gives rise to compressive forces approaching 1,000 atm, and a low-amplitude
      sustained negative pressure (rarefactive) component. Shock waves are created by
      means of three different types of shock wave generators: spark-gap,
      electromagnetic, and piezoelectric. The authors describe and compare these three
      types of shock wave generators with regard to equipment selection. Regardless of
      how shock waves are generated, they share common interactions with tissue. These
      interactions are reviewed along with the proposed mechanisms of stone
      fragmentation.

PMID- 1987601
TI  - Early asbestosis: evaluation with high-resolution CT.
AB  - To determine the earliest stage at which lesions in asbestosis can be diagnosed
      and to assess their progression, 23 asbestos-exposed patients with minimal or no
      abnormalities at plain radiography were examined with high-resolution computed
      tomography (HRCT) twice, with an interval of 12-37 months between examinations.
      In 21 of the patients, parenchymal abnormalities were found. Major parenchymal
      features seen at CT included thickened intralobular and interlobular lines,
      subpleural curvilinear lines, pleural-based nodular irregularities, hazy patches
      of increased attenuation, small cystic spaces, and small areas of low
      attenuation. At paired serial CT, subpleural isolated dots or branching
      structures connected with the most peripheral branch of the pulmonary artery
      started to appear in lower subpleural zones and then became confluent to create
      pleural-based nodular irregularities. CT-pathologic correlation led to the
      conclusion that the confluence of subpleural peribronchiolar fibrosis creates
      subpleural fibrosis.

PMID- 1987602
TI  - Malignancy associated with chronic empyema: radiologic assessment.
AB  - Radiologic findings of six cases of malignancy associated with chronic empyema 5
      39 years in duration were reviewed. Pathologic examination confirmed three B-cell
      non-Hodgkin lymphomas, one round-cell sarcoma, one mesothelioma, and one
      adenocarcinoma. Retrospective findings on plain chest radiographs suggested the
      occurrence of malignancy: increased radiopacity in the thoracic cavity, soft
      tissue bulgings and/or unsharpness of fat planes in the chest walls, destruction
      of bone near the empyema, and extensive medial deviation of the calcified
      pleurae. Computed tomography delineated masses with soft-tissue attenuation more
      clearly than radiography in all cases. Magnetic resonance images of three cases
      were informative because empyema cavities were surrounded by low-intensity rims,
      and two of them showed a signal intensity different from that of necrotic tumors.
      Scintigraphy revealed increased uptake of gallium in all cases. Ultrasonography
      was useful for biopsy guidance. Every radiologist should know this entity in
      observation of chest radiographs obtained in patients with chronic empyema, and
      further radiologic assessment and aggressive biopsy are recommended if malignancy
      is suspected.

PMID- 1987603
TI  - Use of gadolinium-enhanced MR imaging for differentiating mucoceles from
      neoplasms in the paranasal sinuses.
AB  - The purpose of this study was to determine whether additional clinically useful
      information could be obtained from gadolinium-enhanced magnetic resonance (MR)
      imaging compared with the information obtained from nonenhanced MR imaging and
      computed tomography (CT). Therefore, the authors selected 41 patients, whose
      results at CT examinations demonstrated a variety of pathologic conditions of the
      paranasal sinuses, to undergo MR imaging both with and without the use of
      gadopentetate dimeglumine for contrast enhancement. In 22 of 35 cases of
      neoplasms and mucoceles occurring separately, the lesions were correctly
      differentiated by established MR signal criteria alone. However, 32 of these 35
      cases were accurately differentiated when gadolinium-enhanced MR images were
      obtained. Six cases demonstrated co-existing neoplasm and mucocele: Gadolinium
      enhanced MR enabled correct differentiation of five of these lesions, while
      unenhanced MR enabled correct differentiation of three. On the basis of these
      results, the authors conclude that the use of gadopentetate dimeglumine for
      contrast enhancement at MR imaging is useful for differentiating mucoceles from
      neoplasms in the sinonasal tract.

PMID- 1987604
TI  - Differentiation of detached retina and vitreous membrane with color flow Doppler.
AB  - The sonographic criteria for diagnosis of retinal detachment and vitreous
      membranes are well established, and in most cases a diagnosis can be made.
      However, in difficult cases, differentiation between the two may be difficult. In
      this study the use of high-resolution color flow Doppler was evaluated for
      differentiating between retinal detachments and vitreous membranes. Sonographic
      evaluation, including color flow Doppler, was performed in 25 symptomatic eyes.
      Seven eyes had areas of retinal detachment, all of which had detectable blood
      flow within at least a portion of the detached retina. Fifteen eyes had vitreous
      hemorrhages or membranes in which no flow was detected. Two diabetic patients
      with vitreous membranes and no retinal detachment did have flow detectable within
      the neovascular membranes. Another patient, who had a complete choroid detachment
      after surgery, demonstrated good flow within the area of detachment. It is
      concluded that in difficult cases high-resolution color flow Doppler can enable
      differentiation of an area of retinal detachment from a vitreous membrane in a
      patient without diabetes.

PMID- 1987605
TI  - Cerebral infarction: early detection by means of contrast-enhanced cerebral
      arteries at MR imaging.
AB  - The authors describe a new magnetic resonance (MR) imaging sign of acute cerebral
      ischemia/infarction. Abnormally contrast material-enhanced curvilinear structures
      were demonstrated in eight patients in the evolving area of cerebral
      ischemia/infarction within 26 hours after the ictus on contrast-enhanced, high
      field-strength (1.5-T), T1-weighted spin-echo images. The abnormal enhancement is
      considered to represent cortical arterial vessels of markedly slowed circulation
      in areas of underlying brain injury, which will eventually progress to frank
      brain infarction. This was demonstrated at computed tomographic (CT) and follow
      up MR examinations. Characteristically, the degree of the contrast enhancement of
      vessels appeared most intense in the proximal portions, and the intensity of
      enhancement gradually diminished in the more distal portions of these vessels as
      they pass over the convexities and finally disappear.

PMID- 1987606
TI  - Normal and abnormal pituitary glands: gadopentetate dimeglumine-enhanced MR
      imaging.
AB  - Dynamic magnetic resonance (MR) imaging with a 1.5-T superconductive unit was
      used in the evaluation of nine normal pituitary glands and 10 pituitary adenomas,
      including four microadenomas and six macroadenomas. Seven to 10 images were
      obtained every 20-30 seconds with use of the spin-echo technique after rapid
      injection of gadopentetate dimeglumine. The earliest contrast material
      enhancement of normal structures was seen in the infundibulum and posterior lobe
      of the pituitary gland at 20 seconds, followed by gradual contrast material
      enhancement of the anterior lobe of the pituitary gland from the junction of the
      infundibulum to the peripheral portion of the anterior lobe of the pituitary
      gland within 80 seconds after gadopentetate dimeglumine injection. The peak
      enhancement of pituitary adenomas occurred at 60-200 seconds, usually after the
      most marked enhancement of the normal pituitary gland. Microadenomas are best
      visualized at earlier phases of gadopentetate dimeglumine-enhanced dynamic
      imaging, with signal intensity lower than that seen on images of normal pituitary
      glands.

PMID- 1987607
TI  - Multiple sclerosis: specificity of MR for diagnosis.
AB  - The specificity of magnetic resonance (MR) imaging in the diagnosis of multiple
      sclerosis (MS) has not been measured systematically. Conventional MR head images
      with sagittal localizer and axial multiple-echo sequences with long repetition
      times were obtained in 92 patients with clinically verified MS (Schumacher
      criteria), 100 healthy volunteers, 60 subjects with hypertension, and eight
      patients with dementia. Two readers, without the aid of any clinical or
      demographic information, classified each of the 260 studies as MS or not MS. The
      readers classified the studies again after being supplied with the subjects' ages
      and sex. True-negative and true-positive diagnoses of MS were tabulated. The
      specificity of the MR diagnosis of MS (true-negative results in proportion to all
      non-MS studies) was 95%-99% with all the control groups included. There is a
      small risk of misinterpreting incidental periventricular white matter foci as
      plaques of MS in MR studies.

PMID- 1987608
TI  - Cerebral venography with MR.
AB  - The authors describe a two-dimensional time-of-flight magnetic resonance (MR)
      angiography technique to create projection venograms of the head. The technique
      was applied to 27 healthy volunteers and 39 patients. The superior sagittal and
      straight sinuses, the internal cerebral veins, and the Galen vein were visualized
      in all the volunteers. Other veins were seen in a high percentage of subjects.
      Systematic comparison of digital subtraction angiography (DSA) after
      intraarterial contrast medium injection and MR venography in patients showed good
      correlation between the two techniques. MR venography proved helpful in
      identifying thrombosis or patency of cerebral veins and sinuses and showed
      collateral venous drainage and venous drainage from arteriovenous malformations.
      There was good correlation between conventional contrast angiography and MR
      venography. In conclusion, MR venography is considered reliable for showing the
      cerebral venous system and provides information additional to that of
      conventional spin-echo imaging.

PMID- 1987609
TI  - Marked cerebrospinal fluid void: indicator of successful shunt in patients with
      suspected normal-pressure hydrocephalus.
AB  - The authors blindly reviewed the charts of 20 patients with normal-pressure
      hydrocephalus (a disease of unknown cause characterized radiologically as chronic
      communicating hydrocephalus and clinically by gait apraxia, dementia, and
      incontinence) who had undergone creation of a ventriculoperitoneal shunt. The
      initial clinical response to surgery was graded excellent, good, fair, or poor; 5
      year follow-up was available in 55% of cases. The magnetic resonance (MR) images
      obtained in these patients were also blindly reviewed for the magnitude of
      cerebrospinal fluid (CSF) flow void (graded on the basis of extent rather than
      degree of signal loss) in the cerebral aqueduct. A significant (P less than .003)
      correlation existed between good or excellent response to surgery and an
      increased CSF flow void. The presence of associated deep white matter infarction
      on MR images did not correlate with a poor response to surgery. On the basis of
      these findings, it is suggested that patients who fulfill the clinical criteria
      of NPH and have an increased CSF flow void undergo creation of a shunt.

PMID- 1987610
TI  - Normal flow patterns of intracranial and spinal cerebrospinal fluid defined with
      phase-contrast cine MR imaging.
AB  - A phase-contrast cine magnetic resonance (MR) imaging technique was used to study
      normal dynamics of cerebrospinal fluid (CSF) in 10 healthy volunteers and four
      patients with normal MR images. This pulse sequence yielded 16 quantitative flow
      encoded images per cardiac cycle (peripheral gating). Flow encoding depicted
      craniocaudal flow as high signal intensity and caudo-cranial flow as low signal
      intensity. Sagittal and axial images of the head, cervical spine, and lumbar
      spine were obtained, and strategic sites were analyzed for quantitative CSF flow.
      The onset of CSF systole in the subarachnoid space was synchronous with the onset
      of systole in the carotid artery. CSF systole and diastole at the foramen of
      Monro and aqueduct were essentially simultaneous. The systolic and diastolic
      components were different in the subarachnoid space, where systole occupied
      approximately 40% and diastole 60% of the cardiac cycle, compared with the
      ventricular system, where they were equal. This difference results in systole in
      the intracranial and spinal subarachnoid spaces preceding that in the ventricular
      system; the same is true for diastole. The fourth ventricle and cisterna magna
      serve as mixing chambers. The high-velocity flow in the cervical spine and
      essentially no flow in the distal lumbar sac indicate that a portion of the
      capacitance necessary in this essentially closed system resides in the distal
      spinal canal.

PMID- 1987611
TI  - Rectal strictures: treatment with fluoroscopically guided balloon dilation.
AB  - The authors performed 25 fluoroscopically guided balloon dilation procedures in
      nine patients with rectal strictures. In all cases, the stricture developed after
      rectal surgery. Four patients underwent ileoanal anastomosis after total
      colectomy for various conditions; five patients underwent rectosigmoid end-to-end
      anastomosis after resection of a tumor or as treatment for diverticulitis.
      Maximal stricture dilatation was attained in 20 instances with a single 15-30-mm
      balloon. In five procedures, two balloons (20 or 15 mm) were inflated
      simultaneously ("kissing balloons" technique) to dilate the strictures. In five
      patients, only one dilation procedure was required for effective treatment of the
      strictures, with no clinical evidence of strictures after follow-up of 1.5-56
      months (mean, 29.5 months). In the other four patients, multiple procedures were
      performed: nine in one patient, five in one patient, and three in two patients.
      In these patients, no recurrent symptoms developed during follow-up of 1.25-18
      months (mean, 8.1 months) after the last dilation. Complicating leaks, infection,
      or hemorrhage did not occur after any of the procedures. Fluoroscopically guided
      balloon dilation is a safe and effective procedure for the treatment of rectal
      strictures.

PMID- 1987612
TI  - Splenic trauma: can CT grading systems enable prediction of successful
      nonsurgical treatment?
AB  - The capability of computed tomographic (CT) grading systems to enable prediction
      of successful nonsurgical treatment of splenic trauma in children and adults was
      evaluated. Fifty-six patients with documented splenic injury were examined with
      CT by use of standard trauma protocols. Each CT scan was graded according to two
      recently proposed grading systems. The charts of these patients were then
      reviewed, and correlations between the CT grade and clinical outcome were
      determined with each grading system. Forty patients underwent successful
      nonsurgical treatment; three of these patients (8%) underwent delayed celiotomy
      for splenic rupture after failure of nonsurgical treatment. Two of these three
      had grades that indicated nonsurgical treatment was viable. In each of these
      three patients, splenectomy was necessary. In the 16 patients who underwent
      surgery, eight cases (50%) of CT grading errors were documented with surgery. In
      four cases, the extent of the injury was underscored with CT, and in another four
      cases the injury was overscored. It is still not clear whether the severity of
      splenic injury as defined with CT correlates with clinical outcome.

PMID- 1987613
TI  - Air in the fissure for the ligamentum teres: new sign of intraperitoneal air on
      plain radiographs.
AB  - In each of four patients in whom an acute spontaneous pneumoperitoneum developed,
      a vertically directed area of hyperlucency in the right upper quadrant was seen
      on radiographs of the abdomen obtained with the patient supine. This finding,
      which appeared in the absence of other characteristic signs of free air on plain
      radiographs and which, to the authors' knowledge, has not been previously
      recognized, represented intraperitoneal gas confined to the fissure for the
      ligamentum teres (FLT). The location of the hyperlucent area was confirmed with
      computed tomography or laparotomy in each patient. The distinctive configuration
      of air in the FLT is a subtle but reliable indicator of pneumoperitoneum.

PMID- 1987614
TI  - Hepatic dynamic sequential CT: section enhancement profiles with a bolus of ionic
      and nonionic contrast agents.
AB  - The enhancement characteristics in different portions of the liver during dynamic
      sequential bolus computed tomography (CT) with iodinated contrast material
      (DSBCT) were prospectively evaluated in 75 patients by using iothalamate
      meglumine, iopamidol, and iohexol (25 patients received each agent). After
      baseline noncontrast CT was performed, DSBCT was performed with a 180-mL
      intravenous bolus administered at 2 mL/sec. Scanning was started 25 seconds after
      the bolus was initiated, by using a 3-second scan time and rapid cephalocaudal
      table incrementation, yielding contiguous 8-mm-thick sections at a rate of nine
      sections per minute. On postcontrast images, peak enhancement was 115% for
      iopamidol and 117% for iohexol, both of which were superior to iothalamate
      meglumine at 95% (P less than .05). After peaking, enhancement then decreased for
      all three contrast agents, although the decline was more precipitous for
      iothalamate meglumine. Enhancement on the more caudal sections with both
      iopamidol and iohexol was superior to that with iothalamate meglumine (P less
      than .05). The data suggest that the enhancement characteristics for the two
      nonionic agents may be more optimal for detection of focal hepatic lesions than
      the ionic agent.

PMID- 1987615
TI  - Gadopentetate dimeglumine as a bowel contrast agent: safety and efficacy.
AB  - To determine the safety and efficacy of gadopentetate dimeglumine as a bowel
      contrast agent, magnetic resonance (MR) imaging (0.5 T) was performed with a
      formulation of gadopentetate dimeglumine (1.0 mmol/L of gadopentetate
      dimeglumine, 15 g/L of mannitol, 6-17 mL/kg) in 133 patients with intraabdominal
      mass lesions. Mostly short-lived gastrointestinal side effects were noted in 32%
      of patients. Gadopentetate dimeglumine provided uniform hyperintense marking of
      the bowel and contrast enhancement in the region of interest in 81% of patients.
      Among 78 patients with images obtained both before and after administration of
      contrast material, post-contrast improvement of lesion delineation was found in
      62%. Among 55 patients with only postcontrast images, gadopentetate dimeglumine
      proved useful in 65%. Intravenous injection of scopolamine or glucagon
      effectively eliminated "ghost" images of the opacified bowel in 105 of 109 cases.
      The authors conclude that gadopentetate dimeglumine is a safe and effective bowel
      contrast agent for MR imaging.

PMID- 1987616
TI  - Extracorporeal shock wave lithotripsy of gallstones: results and 6-month follow
      up in 141 patients.
AB  - A study of biliary shock wave lithotripsy of gallstones sponsored by Dornier
      Medical Systems, Munich, began in the United States in May 1988 to evaluate the
      efficacy and safety of extracorporeal shock wave lithotripsy (ESWL) and the need
      for adjunctive therapy with ursodeoxycholic acid (UDCA). One hundred forty-one
      symptomatic patients with one to three gallstones 5-30 mm in diameter were
      randomized to treatment. One week before ESWL, patients were given either UDCA or
      placebo. This treatment was continued for 6 months. All patients underwent follow
      up at predetermined intervals. According to the protocol, re-treatment for
      fragments larger than 5 mm in diameter could be performed only at 6 weeks; 26
      (18%) of the 141 patients were retreated. At 6 months, the stone-free rates for
      single stones were as follows: patients with noncalcified stones receiving UDCA,
      29%; patients with noncalcified stones receiving placebo, 24%; and patients with
      partially calcified stones receiving either UDCA or placebo, 6%. No significant
      difference was noted between the UDCA and placebo groups. At 6 months, the stone
      free rates in patients with single, noncalcified stones 20 mm or less in diameter
      were 40% (UDCA) and 32% (placebo), which is superior to rates for those with
      solitary, noncalcified gallstones 21-30 mm in diameter and those with two or
      three stones.

PMID- 1987617
TI  - Liver cirrhosis: changes of Doppler waveform of hepatic veins.
AB  - The authors compared the Doppler ultrasonographic pattern of hepatic veins (HVs)
      in a group of 60 patients affected by liver cirrhosis and in 65 healthy subjects
      comparable for sex and age to (a) detect possible differences in HV waveform in
      the two groups and (b) investigate the relationship of these differences with the
      severity of the disease (according to Child-Pugh classification) and the
      modifications of systemic hemodynamics. The waveform of HVs was arbitrarily
      classified into three patterns: HV0, a normal waveform; HV1, lower oscillations
      without the reversed phase; and HV2, completely flat waveform. The resistivity
      index of the superior mesenteric artery, reflecting the peripheral splanchnic
      impedance and the hyperdynamic circulation, was also measured in a subgroup of 45
      cirrhotic patients. The waveform of HVs in all healthy subjects corresponded to
      the HV0 pattern. Among cirrhotic patients, HV0 was found in 30 (50%), HV1 in 19
      (31.7%), and HV2 in 11 (81.3%). The severity of functional impairment was
      greatest in the HV2 group and least in the HV0 group. This was significantly
      correlated with the decrease of the resistivity index in the superior mesenteric
      artery in the subgroup of 45 patients. Changes in the normal HV waveform could be
      considered a useful adjunctive tool for the noninvasive evaluation of liver
      disease. The pathophysiology of these changes in HV blood flow is still unclear.
      The significant correlation with the severity of the disease and with the
      decrease of splanchnic resistances indicates that these changes in the HV
      waveform occur in the presence of marked rearrangements of liver tissue and of
      hyperdynamic systemic circulation.

PMID- 1987618
TI  - Gastric antral vascular ectasia ("watermelon stomach"): radiologic findings.
AB  - Radiologic findings in a patient with gastric antral vascular ectasia are
      described on computed tomographic scans, upper gastrointestinal series, and
      specimen radiographs. Findings include prominent, scalloped antral folds
      radiating to the pylorus and thickening of the gastric antrum. Pathognomonic red
      vascular folds, likened to stripes on a watermelon, can be seen endoscopically.

PMID- 1987619
TI  - Lymph nodes: microstructural anatomy at MR imaging.
AB  - High-resolution microscopic magnetic resonance (MR) images of rodent lymph nodes
      were directly correlated with sections obtained for histologic study to determine
      the microstructural anatomy of lymph nodes seen at MR imaging and to evaluate
      signal intensity changes induced by a novel intravenous lymphotropic MR contrast
      agent (ultrasmall superparamagnetic iron oxide [USPIO]). High-resolution T2
      weighted images of unenhanced lymph nodes demonstrated medullary sinus as regions
      of low signal intensity and follicles as high-intensity structures. After a
      single intravenous administration of USPIO (160 mumol/kg), both T1-weighted and
      T2-weighted images showed areas of focal signal intensity loss in medullary
      sinuses corresponding to the distribution of uptake by macrophages. Lymph
      follicles appeared unchanged in signal intensity, as they are largely devoid of
      macrophages. This model of microscopic MR imaging should provide the basis for
      (a) understanding differences between patterns of contrast-enhanced normal lymph
      nodes and those of diseased ones and (b) guiding the development of targeting
      strategies for novel pharmaceuticals at the cellular level.

PMID- 1987620
TI  - Nonpalpable prostate cancer: detection with MR imaging.
AB  - The pathologic specimens and magnetic resonance (MR) images of 53 patients with
      clinically palpable prostate cancer confined to one lobe were studied to evaluate
      the ability of MR imaging to depict clinically nonpalpable prostate cancer. All
      patients had undergone imaging with a 1.5-T imager with T1- and T2-weighted
      sequences in both axial and sagittal planes before undergoing radical retropubic
      prostatectomy. At pathologic examination, only the palpable tumor was present in
      30 of the 53 patients (57%), and 33 unsuspected tumors were present in an area
      distinct from the palpable tumor in 23 of the patients (43%). MR imaging
      successfully depicted 51 palpable tumors for a sensitivity of 96% and 19 of the
      33 unsuspected tumors for a sensitivity of 58%. The sensitivity of MR imaging in
      the detection of nonpalpable, posteriorly located tumors was greater than for
      those located anteriorly (85% vs 15%). MR imaging was false-positive for
      nonpalpable tumor in 17 of 30 patients for a specificity of 43%. On the basis of
      these data, MR imaging has greater sensitivity in the depiction of posteriorly
      located cancer and is limited by a high false-positive rate in the depiction of
      nonpalpable tumors.

PMID- 1987621
TI  - Renal artery stenosis: in vivo perfusion MR imaging.
AB  - The intravoxel incoherent motion (IVIM) model of perfusion and diffusion imaging
      was applied to an in vivo canine model of unilateral renal artery stenosis and
      was compared with relative renal blood flow determination with radioactive
      microspheres. The percentage relative renal blood flow as determined with
      radioactive microspheres correlated closely with the percentage apparent
      diffusion coefficient. If this method can be adapted to human imaging, it may
      provide a noninvasive means for detecting renal artery stenosis.

PMID- 1987622
TI  - Gynecologic vascular abnormalities: diagnosis with Doppler US.
AB  - The authors describe the use of duplex and/or color Doppler ultrasonography of
      the pelvis in three women to demonstrate the presence of venous malformations.
      One patient with a pulsatile vaginal mass was shown to have an arteriovenous
      malformation of the vaginal wall. The second patient was shown to have an
      unsuspected venous angioma in the endometrial cavity. The third patient was shown
      to have adnexal varices that closely mimicked hydrosalpinx. In the latter two
      cases, the duplex and color flow capabilities of an endovaginal probe were
      especially important.

PMID- 1987623
TI  - Anterior cruciate ligament reconstruction: evaluation with MR imaging.
AB  - Fifty magnetic resonance (MR) imaging examinations were performed in 37 patients
      after arthroscopic anterior cruciate ligament (ACL) reconstruction with patellar
      bone-tendon-tibial bone autografts. T1-weighted sagittal and axial images were
      obtained. In 34 patients with clinically stable ACL autografts, 43 of 47 MR
      examinations demonstrated a well-defined, intact ACL autograft. All three
      patients with ACL laxity failed to demonstrate a well-defined autograft, for an
      overall correlation between MR imaging and clinical examination results of 92%.
      Of the 12 patients who underwent second-look arthroscopy, 100% correlation was
      present between MR imaging and arthroscopic results. As in the nonreconstructed
      knee, buckling of the posterior cruciate ligament was suggestive of ACL laxity.
      MR imaging also documented optimum placement of bone tunnels in the femur and
      tibia. MR imaging has proved to be an excellent noninvasive imaging modality for
      evaluating ACL reconstruction, while also providing ancillary information about
      the postoperative knee.

PMID- 1987624
TI  - Knee hyaline cartilage evaluated with MR imaging: a cadaveric study involving
      multiple imaging sequences and intraarticular injection of gadolinium and saline
      solution.
AB  - Magnetic resonance (MR) imaging of cadaveric knees was performed to determine
      optimal sequences for visualization of hyaline cartilage. Six fresh-frozen
      cadaveric knees were imaged with a 1.5-T imager by means of standard and hybrid
      fat suppression (HFS) spin-echo techniques, with and without intraarticular
      injection of saline solution and gadopentetate dimeglumine. The knees then were
      sectioned at 4-mm intervals. Both the real and the imaged cartilage thicknesses
      were measured. Areas of cartilage thinning and focal defects seen in the
      cadaveric sections were most accurately matched, in both the presence and the
      absence of intraarticular saline solution simulating joint fluid, by images
      obtained with the T1-weighted HFS sequences. Accurate imaging of hyaline
      cartilage thickness with differentiation of cartilage from fluid was possible
      routinely. Standard and HFS spin-echo images obtained after intraarticular
      injection of gadopentetate dimeglumine depicted cartilage less accurately than
      HFS sequences either with or without saline injection. MR imaging with T1
      weighted HFS sequences provided superior visualization of cartilage, enabling
      accurate measurements of cartilage thickness and differentiation of cartilage
      from saline solution simulating joint fluid.

PMID- 1987625
TI  - Bullet identification with radiography.
AB  - The authors provide a simple radiographic method for estimating bullet weight and
      caliber of both deformed and undeformed bullets that enables accurate
      determination of caliber for the gamut of bullet shapes, with known degrees of
      confidence. The weight-determination procedure is based on the correlation
      between bullet cross-sectional area, as derived from three orthogonal
      radiographs, and bullet weight, as determined from a data base of the properties
      of 48 bullets removed from humans. Different equations were developed for bullets
      weighing 5.8 g or less, or more than 5.8 g. For relatively undeformed bullets an
      additional method calculated caliber directly from the diameter of the bullet
      body on radiographs. Both methods enabled correct prediction of the weight and
      caliber of the bullets; if one method could not be used, results of the other
      were reliable. Testimony based on these results has been accepted in a local
      police case and may meet requirements for testimony in U.S. court cases involving
      gunshots.

PMID- 1987626
TI  - Pterygia: single-fraction postoperative beta irradiation.
AB  - A retrospective evaluation was performed with records of 128 patients with 146
      eyes that underwent applications of strontium-90 after pterygium excisions
      performed between 1982 and 1988. With a median follow-up of 13 months, 135 eyes
      were evaluable. Most pterygia (127 of 135) were treated with a single
      postoperative application of Sr-90 that delivered 3,000 cGy of beta radiation in
      one fraction. The actuarial freedom from relapse was 87%; all recurrences
      occurred within the first 18 months, and 46% of these within the first 3 months.
      Of the 13 recurrences, 10 have been re-treated with surgery and a second course
      of beta irradiation with excellent results. All eight eyes for which follow-up
      was available had no evidence of disease. The ultimate control rate was 96.3% for
      the series. Correlation of various treatment parameters, including age,
      bilaterality, prior recurrence, and interval from surgery to irradiation, was
      performed, and no statistically significant difference was seen. No serious
      complications have developed. Transient conjunctivitis and photophobia were
      almost universally seen, with five cases lasting beyond 5 months. The authors
      conclude that a single application of Sr-90 after surgery is effective and safe
      in managing pterygia.

PMID- 1987627
TI  - Sacral foramina: view at CT.
AB  - Conventional transaxial computed tomography (CT) is superior to plain radiography
      in depicting the sacrum. Because of the shape and orientation of the sacrum, CT
      provides oblique views of the structures of interest. With easily reproducible
      landmarks and standard transaxial CT data, orthogonal image sets can be produced
      that provide a true en face orientation matching the obliquity of the sacrum.
      This allows optimal visualization of the paired foramina and of the sacroiliac
      joints for better assessment of trauma, tumor, or inflammatory disease.

PMID- 1987628
TI  - Relocatable Gianturco expandable metallic stents.
AB  - The authors modified Gianturco expandable metallic stents to make them
      relocatable. Two tandem designs were made. The first design had long struts and,
      thus, more evenly distributed expansive force; the second had short struts and
      more flexibility and was better suited for use in curved strictures. Both designs
      (two to four in tandem, 0.012-, 0.014-, and 0.018-inch wire) were tested
      successfully in vitro, and both designs (two to four in tandem, 0.012-inch wire)
      were successfully placed, retrieved, and relocated in the inferior vena cava of
      five dogs.

PMID- 1987629
TI  - Open-floored concave compensating filter for angiography.
AB  - An open-floored concave compensating filter was designed that produced a
      radiograph of uniform density, caused no artifacts due to its shape or position,
      and required little or no increase in exposure in most applications. Selective
      celiac, hepatic, shoulder, and pelvic angiography was performed with use of the
      filter; image quality was noticeably improved.

PMID- 1987630
TI  - Fibrinolytic therapy for upper extremity occlusions.

PMID- 1987631
TI  - Marrow repopulation after bone marrow transplantation.

PMID- 1987633
TI  - Lightening dark radiographs.

PMID- 1987632
TI  - Inappropriate use of a chi 2 test in modality comparison study of related
      samples.

PMID- 1987634
TI  - Extrapulmonary Pneumocystis carinii infection: another cause of splenic "bull's
      eye" lesions.

PMID- 1987635
TI  - Carcinogenesis models.

PMID- 1987636
TI  - Methylation-sensitive sequence-specific DNA binding by the c-Myc basic region.
AB  - The function of the c-Myc oncoprotein and its role in cell growth control is
      unclear. A basic region of c-Myc is structurally related to the basic motifs of
      helix-loop-helix (HLH) and leucine zipper proteins, which provide sequence
      specific DNA binding function. The c-Myc basic region was tested for its ability
      to bind DNA by attaching it to the HLH dimerization interface of the E12 enhancer
      binding factor. Dimers of the chimeric protein, termed E6, specifically bound an
      E box element (GGCCACGTGACC) recognized by other HLH proteins in a manner
      dependent on the integrity of the c-Myc basic motif. Methylation of the core CpG
      in the E box recognition site specifically inhibited binding by E6, but not by
      two other HLH proteins. Expression of E6 (but not an E6 DNA binding mutant)
      suppressed the ability of c-myc to cooperate with H-ras in a rat embryo
      fibroblast transformation assay, suggesting that the DNA recognition specificity
      of E6 is related to that of c-Myc in vivo.

PMID- 1987638
TI  - Safety of bovine growth hormone.

PMID- 1987637
TI  - Coordinate regulation of beta-lactamase induction and peptidoglycan composition
      by the amp operon.
AB  - The amp operon, which is located on the Escherichia coli chromosome, modulates
      the induction of plasmid-borne beta-lactamase genes by extracellular beta-lactam
      antibiotics. This suggests that the gene products AmpD and AmpE may function in
      the transduction of external signals. beta-Lactam antibiotics are analogs of cell
      wall components that can be released during cell wall morphogenesis of
      enterobacteria. The amp operon was studied to determine its importance in signal
      transduction during cell wall morphogenesis. The peptidoglycan compositions of
      amp mutants were determined by high-performance liquid chromatography and fast
      atom bombardment mass spectrometry. When a chromosomal or plasmid-borne copy of
      ampD was present, the amount of pentapeptide-containing muropeptides in the cell
      wall increased upon addition of the cell wall constituent diaminopimelic acid to
      the growth medium. These results suggest that beta-lactamase induction and
      modulation of the composition of the cell wall share elements of a regulatory
      circuit that involves AmpD. Escherichia coli requires AmpD to respond to
      extracellular signaling amino acids, such as diaminopimelic acid, and this signal
      transduction system may regulate peptidoglycan composition in response to cell
      wall turnover products.

PMID- 1987639
TI  - Interpreting cancer tests.

PMID- 1987641
TI  - Third strike for Idaho reactor.

PMID- 1987640
TI  - Kidney transplantation: overlooked pioneer.

PMID- 1987642
TI  - Healy nominated.

PMID- 1987643
TI  - GAO and DOD get into a cat fight.

PMID- 1987644
TI  - CCAAT-enhancer binding protein: a component of a differentiation switch.
AB  - The CCAAT-enhancer binding protein (C/EBP) has now been found to promote the
      terminal differentiation of adipocytes. During the normal course of adipogenesis,
      C/EBP expression is restricted to a terminal phase wherein proliferative growth
      is arrested, and specialized cell phenotype is first manifested. A conditional
      form of C/EBP was developed, making it feasible to test its capacity to regulate
      the differentiation of cultured adipocytes. Premature expression of C/EBP in
      adipoblasts caused a direct cessation of mitotic growth. Moreover, when abetted
      by the effects of three adipogenic hormones, C/EBP promoted terminal cell
      differentiation. Since C/EBP is expressed in a variety of tissues, it may have a
      fundamental role in regulating the balance between cell growth and
      differentiation in higher animals.

PMID- 1987645
TI  - Altered perception of species-specific song by female birds after lesions of a
      forebrain nucleus.
AB  - Female birds that do not normally sing possess brain nuclei associated with song
      production in males. To determine whether one song nucleus, the caudal nucleus of
      the ventral hyperstriatum (HVc), acts in conspecific song perception, courtship
      responses of female canaries to canary and white-crowned sparrow songs were
      compared before and after HVc lesions. Bilateral lesions of a portion of the HVc
      resulted in copulation solicitations to heterospecific song as well as
      conspecific song. Control females continued to respond only to conspecific song.
      This suggests that the HVc is critical for conspecific song perception in
      females. Because female canaries do not normally sing, neurons in female HVc must
      develop response selectivity by a mechanism different from that proposed for male
      birds in the motor theory of song perception.

PMID- 1987646
TI  - The effect of anti-neoplastic drugs on murine acquired immunodeficiency syndrome.
AB  - The murine acquired immunodeficiency syndrome (MAIDS) is associated with
      proliferation of target cells that have been infected by a defective retrovirus.
      To control the growth of this primary neoplasia, virus-inoculated mice were
      treated with anti-neoplastic drugs. Paradoxically, cyclophosphamide, which is
      also immunosuppressive, was very effective in preventing the appearance and
      progression of the disease, in restoring a normal T cell function, and in
      depleting the number of infected target cells. This result suggests that the
      proliferating infected target cells were responsible for the immunodeficiency.

PMID- 1987647
TI  - Evidence for biased gene conversion in concerted evolution of ribosomal DNA.
AB  - Concerted evolution is the production and maintenance of homogeneity within
      repeated families of DNA. Two mechanisms--unequal crossing over and biased gene
      conversion--have been the principal explanations of concerted evolution.
      Concerted evolution of ribosomal DNA (rDNA) arrays is thought to be largely the
      result of unequal crossing over. However, concerted evolution of rDNA in
      parthenogenetic lizards of hybrid origin is strongly biased toward one of two
      parental sequences, which is consistent with biased gene conversion as the
      operative mechanism. The apparent gene conversions are independent of initial
      genome dosage and result in homogenization of rDNA arrays across all nucleolar
      organizer regions.

PMID- 1987648
TI  - The effect of the floor plate on pattern and polarity in the developing central
      nervous system.
AB  - The effect of floor plate on cellular differentiation in the neural tube of quail
      embryos was examined. In the developing neural tube the floor plate, which
      consists of specialized neuroepithelial cells, is located in the ventral midline
      of the neural tube. When Hensen's node was extirpated the floor plate and
      notochord did not develop, and the normal differentiation of the ventral horn
      motor neurons and dorsal and ventral roots did not occur. When one side of the
      neural tube was deprived of notochord, the ventro-dorsal differentiation took
      place on both sides. However, when one side of the neural tube was deprived of
      the floor plate, the ventral horn motor neurons and dorsal and ventral roots did
      not develop on that side. These observations suggest that the floor plate
      influences motor neuron differentiation and acts as an intrinsic organizer to
      establish pattern and polarity in the developing nervous system.

PMID- 1987649
TI  - Lipid flow in locomoting cells.

PMID- 1987650
TI  - Evidence against deacetylation and for cytochrome P450-mediated activation in
      acetaminophen-induced nephrotoxicity in the CD-1 mouse.
AB  - Acetaminophen (APAP) administration (600 mg/kg, po) results in proximal tubular
      necrosis in 18-hr fasted, 3-month-old male CD-1 mice. This study was undertaken
      to determine if deacetylation of APAP to p-aminophenol (PAP) is a prerequisite to
      nephrotoxicity in the mouse, as it is in the Fischer rat. Administration of
      either APAP or PAP to mice resulted in significant elevations of plasma urea
      nitrogen and marked proximal tubular necrosis at 12 hr after dosing. Prior
      inhibition of APAP deacetylation by the carboxylesterase inhibitors bis(p
      nitrophenyl) phosphate or tri-o-tolyl-phosphate did not alter APAP hepatotoxicity
      or nephrotoxicity. By contrast, pretreatment with the MFO inhibitor piperonyl
      butoxide decreased APAP nephrotoxicity but not that of PAP. Immunochemical
      analysis of kidneys from APAP-treated mice demonstrated covalently bound APAP but
      no binding was detected after mice were treated with a nephrotoxic dose of PAP.
      Since the antibody used has been characterized as being directed primarily
      against the N-acetyl moiety of bound APAP metabolite and since it did not react
      with kidney proteins of mice given a nephrotoxic dose of PAP, it is unlikely that
      APAP deacetylation preceded binding or that acetylation of bound PAP occurred.
      Taken together, these findings indicate that in the CD-1 mouse, APAP-induced
      nephrotoxicity differs from that previously described for the Fischer rat and
      likely involves cytochrome P450-dependent activation and subsequent covalent
      binding of a metabolite without prior deacetylation.

PMID- 1987651
TI  - Vitamin A deficiency and the induction of cutaneous toxicity in murine skin by
      TCDD.
AB  - The mechanisms involved in the induction of toxicity by 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD), a prototype for a group of toxic
      polyhalogenated aromatic hydrocarbons, are largely unknown. To test the
      hypothesis that TCDD-induced toxicity involves the reduction of vitamin A levels,
      we investigated the role of vitamin A deficiency in modulating the cutaneous
      response of congenic haired (+/+) and hairless (hr/hr) mice to TCDD. Hairless
      mice are recognized as sensitive models for expression of TCDD-induced cutaneous
      toxicity. Haired mice normally do not develop a cutaneous response to TCDD. Mice
      raised on a vitamin A-deficient diet, and age- and sex-matched controls raised on
      standard chow, were treated topically with TCDD and their cutaneous responses
      monitored histologically. Body weights and thymus gland weights were monitored as
      additional parameters of toxicity. Liver and skin vitamin A levels were
      determined by HPLC. Vitamin A depletion by itself had no effect on the normal
      cutaneous histology of the haired phenotype, nor were any changes in cutaneous
      morphology attributable to TCDD toxicity observed in haired, TCDD-treated animals
      even when they were severely vitamin A depleted. On the other hand, in hairless
      mice, vitamin A deficiency caused a distinct increase in keratinization of dermal
      epithelial cysts, and an increase in the sensitivity of these cysts to TCDD
      induced hyperkeratinization. TCDD-induced body weight loss and atrophy of the
      thymus gland were not affected by the vitamin A status of either the haired or
      hairless animals. Analysis of vitamin A levels in skin and liver, following
      topical treatment of mice with TCDD, indicated that TCDD exposure did not affect
      cutaneous levels, but did significantly lower liver levels of vitamin A. These
      experiments suggest that although systemic vitamin A deficiency may potentiate
      the expression of TCDD-induced toxicity in skin of hairless mice, expression of
      TCDD-induced toxicity probably involves more complex mechanisms than a reduction
      in vitamin A levels.

PMID- 1987652
TI  - The effect of short term feeding of the antioxidant triethyleneglycol-bis-3(3
      tert-butyl-4-hydroxy-5-methyl)propionate on serum thyrotropin and thyroid
      hormones in the male rat.
AB  - Male rats were fed triethyleneglycol-bis-3(3-tert-butyl-4-hydroxy-5
      methyl)propionate (TK 12627) admixed with the food at a concentration of 1000 ppm
      for 3, 6, 13, and 20 days. Treatment resulted in time-dependent and marked
      increases in serum levels of thyrotropin (TSH) and reverse triiodothyronine
      (rT3). Serum levels of thyroxine (T4) were slightly and transiently decreased,
      whereas triiodothyronine (T3) levels decreased by 35-50% at all time periods.
      Treatment with 50, 150, 500, and 1000 ppm for 2 weeks resulted in dose-related
      increases in thyroid and liver weights, follicular hypertrophy of the thyroid,
      morphological changes of the pituitaries, liver hypertrophy, and similar changes
      in the serum parameters described above. At 50 ppm, no alterations in the weights
      and morphology of the liver, thyroid, or pituitary nor in the serum levels of TSH
      or T4 were observed. The effects of TK 12627 observed at a dose of 1000 ppm for 2
      weeks were reversible after cessation of treatment. Decreases in T3, increases in
      rT3, and no change in T4 serum levels were also obtained when thyroidectomized T4
      substituted rats were treated with 1000 ppm TK 12627 for 28 days, indicating that
      the effects of TK 12627 are probably due to inhibition of the 5' monodeiodination
      of T4 to T3 and rT3 to diiodothyronine with compensatory increases in thyroid
      hormone conjugation at extrathyroidal sites.

PMID- 1987653
TI  - Teratogenic effects of 2,3,7,8-tetrabromodibenzo-p-dioxin and three
      polybrominated dibenzofurans in C57BL/6N mice.
AB  - Brominated flame retardants involved in many industrial uses contain
      polybrominated dibenzo-p-dioxins (PBDDs) and dibenzofurans (PBDFs) as
      contaminants. The levels of these contaminants can be dramatically increased by
      combustion. These chemicals are closely related in structure to the
      polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs), of which
      2,3,7,8-tetrachloridibenzo-p-dioxin (TCDD) is the most toxic isomer. TCDD and
      related PCDFs are potent mouse teratogens inducing cleft palate and
      hydronephrosis at doses below those at which overt maternal and embryo/fetal
      toxicity occurs. This study examines the teratogenic effects of 2,3,7,8
      tetrabromodibenzo-p-dioxin (TBDD), 2,3,7,8-tetrabromodibenzofuran (TBDF),
      1,2,3,7,8-pentabromodibenzofuran (1PeBDF), and 2,3,4,7,8-pentabromodibenzofuran
      (4PeBDF) in C57BL/6N mice treated on gestation day (gd) 10 and examined on gd 18.
      Pregnant dams were treated with 0-4000 micrograms of each congener per kilogram
      body weight in 10 ml corn oil/kg. Dose selection was based on the relative
      toxicity of the chlorinated isomers. Maternal toxicity and developmental toxicity
      were assessed, and the hard palate and kidney, the target organs for the
      teratogenic effects of TCDD and related compounds, were examined for structural
      abnormalities. While the maternal liver weight increased at all dose levels
      examined for all four compounds, there was no evidence of any maternal toxicity.
      Embryo/fetal mortality was increased only at greater than or equal to 500
      microgram TBDF/kg, while fetal weight increased in a dose-related manner
      following exposure to TBDD and TBDF. All compounds produced hydronephrosis (HN)
      at doses below that at which cleft palate (CP) occurred. The incidence of HN was
      significantly increased above background levels at the following doses
      (micrograms/kg): TBDD, 3; TBDF, 25; 1PeBDF, 500; 4PeBDF, 400. The LOELs
      (micrograms/kg) for CP were: TBDD, 48; TBDF, 200; 1PeBDF, 4000; 4PeBDF, 2400. The
      cleft palate incidence for all four brominated compounds and TCDD could be fit to
      a common slope, compatible with the concept that these chemicals all exert their
      teratogenic effects through a common mechanism. The potency of these chemicals,
      relative to TCDD as 1 for the induction of cleft palate, is TBDD, 0.24; TBDF,
      0.10; 1PeBDF, 0.004; and 4PeBDF, 0.005. Previous studies from our laboratory had
      determined that the chlorinated dibenzofuran isomers had relative potencies of
      0.05 (TCDF), 0.03 (1PeCDF), and 0.09 (4PeCDF). Thus, bromination decreases the
      teratogenic activity of TBDD relative to TCDD and of both 1- and 4PeBDF relative
      to the chlorinated isomers. However, substitution of bromines for chlorines
      increases the potency of TBDF relative to TCDF.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1987654
TI  - Aluminum distribution into brain and liver of rats and rabbits following
      intravenous aluminum lactate or citrate: a microdialysis study.
AB  - Microdialysis probes were utilized to follow the appearance and disappearance of
      dialyzable aluminum (Al) in rat and rabbit brain and liver extracellular fluid
      compared to blood after iv Al lactate or Al citrate injection. Dialyzable Al was
      assumed to be the fraction not protein bound or self-associated into complexes
      greater than the molecular weight cutoff of the dialysis membrane. Aluminum
      concentrations peaked in brain frontal cortex and ventral hippocampus and in the
      liver in the first 20-min dialysis sample, indicating rapid Al penetration into
      the extracellular space of these organs. In vitro recovery experiments conducted
      with microdialysis probes at room temperature revealed an average dialysis
      efficiency of about 10% for both Al lactate and citrate. At 37 degrees C Al
      recovery increased for both Al lactate and citrate. In vivo Al recovery from
      rabbit blood averaged 5.15% for Al lactate and 3.25% for Al citrate. These
      observations are consistent with results from recovery studies of other
      substances showing an increased recovery with increased temperature but an
      overestimate of recovery by in vitro methods. Tissue/blood Al ratios (TBR;
      representing dialyzable extracellular tissue Al divided by dialyzable blood
      plasma Al) for liver were approximately 1, suggesting unhindered diffusion of Al
      between blood and liver. In contrast, brain TBR were less than 1, demonstrating a
      partial blood-brain barrier to Al. The brain TBR for Al lactate was greater than
      TBR for Al citrate, suggesting that Al citrate did not preferentially penetrate
      the blood-brain barrier. Higher TBR were seen in the rabbit than the rat, perhaps
      contributing to the greater susceptibility of the rabbit to Al-induced
      neurobehavioral toxicity. Metals can be repetitively sampled in the extracellular
      space using microdialysis, enabling metal toxicokinetic determinations in these
      compartments.

PMID- 1987655
TI  - Comparative effects of disulfiram and N-methyltetrazolethiol on spermatogenic
      development in young CD rats.
AB  - N-Methyltetrazolethiol (NMTT) and NMTT-containing cephalosporin antibiotics cause
      characteristic testicular lesions in young but not adult rats. In addition, NMTT
      containing cephalosporins inhibit aldehyde dehydrogenase and have been associated
      with a disulfiram-like reaction in humans and animals. Therefore, the potential
      testicular toxicity of disulfiram (10, 30, or 100 mg/kg) was evaluated in 37-day
      old rats given oral doses on Postpartum Days 6 through 36, and was compared to
      the toxicity induced by NMTT (100 mg/kg). NMTT and each dose of disulfiram caused
      a decrease in testes weight. By DNA flow cytometry, testicular cell suspensions
      from rats given 100 mg/kg of NMTT had a 40% reduction in spermatids while those
      from rats given 10, 30, or 100 mg/kg of disulfiram had reductions of 52, 61, or
      89%, respectively. Microscopically, the testes of rats given either NMTT or
      disulfiram had qualitatively similar changes, characterized by delayed maturity
      of the leading waves of germinal cells which had reached early maturation phase
      in control animals. Moderate to severe reduction occurred in the total number of
      spermatids with complete absence of acrosome phase and maturation phase
      spermatids. There was also a prominent reduction in the number of spermatocytes.
      Reduction in number of spermatogonia was minimal. While the mechanism of toxicity
      is not known for either compound, it is possible that the toxicity was related to
      the enzyme-inhibitory effects which both compounds possess. By defining the
      mechanism of testicular toxicity for compounds which cause a NMTT-like testicular
      toxicity in rats, biological differences in the spermatogenic process between the
      young and adult rat may be further understood. Direct extrapolation of the
      testicular effects in neonatal rats to man is not possible because of the
      substantial differences in initiation of spermatogenesis between rodents and
      humans.

PMID- 1987656
TI  - Inhibition of interleukin-2 production in the human T cell line JURKAT by
      nonpolar maleimides.
AB  - The immunosuppressive properties of polar and nonpolar maleimides were studied by
      measuring their ability to inhibit mitogen-induced interleukin-2 (IL-2)
      production by JURKAT T cells. The nonpolar maleimides N-ethylmaleimide (NEM) and
      N-phenylmaleimide (NPM) inhibited IL-2 production by 85-99%, but only when added
      to JURKAT cells prior to the mitogen. The polar maleimides N-hydroxymaleimide
      (NHM) and 4-maleimidosalicylic acid (M84) did not suppress IL-2 production
      significantly, even though NHM reacted with more cellular thiols (12%) than did
      NPM (8%). Both NEM and NPM suppressed IL-2 production at doses that did not
      affect proliferation. NEM inhibited IL-2 production induced by PHA, anti-CD3
      (alpha CD3) monoclonal antibodies or PMA, and A23187, but did not interfere with
      the binding of alpha CD3 to the cells. NEM inhibited IL-2 production at
      concentrations that did not interfere with the PHA-induced increase in
      intracellular free calcium [( Ca]i). Neither NPM nor NHM inhibited the rise in
      [Ca]i, even at the highest concentrations tested. Although JURKAT T cells require
      both PMA and A23187 to induce IL-2 production, we found that cells pretreated
      with PMA could respond to A23187 added 18 hr later. PMA-treated cells were not
      resistant to the immunosuppressive effects of NEM or NPM. However, PMA-pretreated
      cells became resistant to the inhibitory effects of NEM upon the addition of
      A23187, suggesting that nonpolar maleimides inhibit activation events induced by
      the rise in [Ca]i.

PMID- 1987657
TI  - The protective effect of metallothionein on the toxicity of various metals in rat
      primary hepatocyte culture.
AB  - Metallothionein (MT), a low-molecular-weight, cysteine-rich, metal-binding
      protein, has been implicated in the detoxification of Cd. However, whether MT
      protects against the cellular toxicity of other metals has not been examined
      thoroughly. This study was therefore designed to determine the effects of Zn
      induced MT on the toxicity of seven metals in rat primary hepatocyte cultures.
      Hepatocytes were grown in monolayer culture for 22 hr and subsequently treated
      with ZnCl2 (100 microM) for 24 hr which produced a 15-fold increase in MT
      concentration. Following Zn pretreatment, hepatocytes were exposed to various
      concentrations of Ag, Co, Cu, Hg, Ni, Pb, or Zn for 24 hr. Cytotoxicity was
      assessed by enzyme leakage and loss of intracellular K+. The toxicity of all
      seven metals was significantly less in the Zn-pretreated cells. Zn pretreatment
      had no appreciable effect on the hepatocellular uptake (1-24 hr) of 110Ag or
      203Hg, but markedly altered their subcellular distribution, with metals
      accumulating more in the cytosol and less in the nuclear, mitochondrial, and
      microsomal fractions. In the cytosol of control cells, the metals were bound
      mainly to high-molecular-weight proteins whereas in the Zn-pretreated cells, the
      metals were mainly associated with MT. In summary, Zn-induced MT in rat primary
      hepatocyte cultures protects against Ag-, Co-, Cu-, Hg-, Ni-, Pb-, and Zn-induced
      cytotoxicity. This protection appears to be due to the binding of metals to MT
      with a concomitant reduction of metal content in critical organelles and
      proteins.

PMID- 1987658
TI  - Light and electron microscopic evidence of tri-o-cresyl phosphate (TOCP)-mediated
      testicular toxicity in Fischer 344 rats.
AB  - The onset and development of testicular lesions following tri-o-cresyl phosphate
      (TOCP) dosing have been documented through light and electron microscopic
      morphological studies. Male Fischer 344 rats (190-210 g body weight) were
      administered 150 mg TOCP/kg/day in corn oil for 1, 3, 5, 7, 10, 14, and 21 days.
      Vehicle-treated rats served as the control group. Sections of formaldehyde- and
      glutaraldehyde-fixed, methacrylate-embedded testes showed, by Day 5, numerous
      spermatid heads apparently detached from tails lying at oblique angles near the
      basement membrane of the seminiferous tubules. Columnar and spherically shaped
      vacuoles of the epithelium, radiating from the basement membrane to the lumen of
      the tubules, were also observed. Electron micrographs revealed that these were
      localized in Sertoli cells. Widespread dilation of Sertoli cell smooth
      endoplasmic reticulum was also noted. By 7 days of treatment, residual body
      abnormalities were noted in stage VIII tubules, along with spermatocyte-derived
      multinucleated giant cells. The lesion progressed with increased vacuolation of
      the epithelium and numbers of abnormal residual bodies and giant cells, together
      with spermatid karyorrhexis (Days 10, 14, and 21). There was also an apparent
      decrease in sperm density/tubule with continued exposure: 90% of the seminiferous
      tubules were devoid of sperm by Day 14. These morphological results indicate an
      initial effect of TOCP on Sertoli cells. Spermatogenesis is affected as seen by
      the decrease in sperm density and increase in necrotic spermatids.

PMID- 1987659
TI  - The synergism of atropine and the cholinesterase reactivator HI-6 in
      counteracting lethality by organophosphate intoxication in the rat.
AB  - Rats were intoxicated with two different S-aminoalkyl-phosphonothioate
      cholinesterase inhibitors, viz. I-1 (S-diethylaminoethyl-O-cyclohexyl-methyl
      phosphonothioate), which has a mixed central/peripheral mode of action, and I-2,
      the methiodide derivative of I-1, which acts almost solely peripherally. It was
      found that atropine did not have any beneficial effect on lethality in the case
      of an I-2 intoxication but did so, although only slightly, in the case of I-1.
      Therefore, the effect of atropine against I-1 intoxications must be mediated
      through central mechanisms, the peripheral parasympatholytic effect being
      negligible in counteracting lethality. Furthermore atropine antagonized the
      convulsions caused by intoxication with I-1. The oxime used as a reactivator of
      inhibited acetylcholinesterase, HI-6, was more effective than atropine against
      either organophosphate. In the case of an I-2 intoxication HI-6 proved extremely
      active. It is, therefore, concluded that HI-6 acts mainly peripherally. It was
      also found that HI-6 has a slight anticonvulsive action. The combination of HI-6
      and atropine had a large synergistic effect in the case of I-1, but in the case
      of I-2 hardly any synergism was observed. Obviously, the combination of the oxime
      and atropine is particularly effective when the toxicant has a mixed
      central/peripheral action. In such intoxications the acetylcholinesterase
      reactivation in the respiratory neuromuscular synapse by the oxime is
      supplemented by the central action of atropine, which improves respiratory
      control at the level of the central nervous system.

PMID- 1987660
TI  - Role of lipid peroxidation in renal proximal tubule cell death induced by
      haloalkene cysteine conjugates.
AB  - The role of lipid peroxidation in the cell death produced by the haloalkene
      cysteine conjugates S-(1,2,3,4,4-pentachlorobutadienyl)-L-cysteine (PCBC), S-(1,2
      dichlorovinyl)-L-cysteine (DCVC), S-(1,1,2,2-tetrafluoroethyl)-L-cysteine (TFEC),
      and S-(2-chloro-1,1,2-trifluoroethyl)-L-cysteine (CTFC) was investigated using a
      well-defined suspension of rabbit renal proximal tubules. PCBC, DCVC, TFEC, and
      CTFC at a concentration of 25 microM caused renal proximal tubular death
      (measured by lactate dehydrogenase release) in a time-dependent (2-6 hr) manner
      and increased tubular malondialdehyde (MDA) formation prior to and during cell
      death (1-6 hr). The antioxidants butylated hydroxytoluene (BHT) (25 microM) and
      N,N'-diphenyl-1,4-phenylenediamine (DPPD) (50 microM) and the iron chelator
      deferoxamine (1 mM) blocked the increase in MDA formation produced by these four
      compounds. BHT and deferoxamine delayed PCBC-, DCVC-, and CTFC-induced cell death
      but had no effect on the overall extent of cell death. BHT and deferoxamine had
      no effect on TFEC-induced cell death. DPPD had effects similar to those of
      deferoxamine on DCVC- and CTFC-induced cell death, but, unlike deferoxamine, DPPD
      significantly reduced PCBC- and TFEC-induced cell death. This difference in the
      effect of DPPD may not be related to its effects as an antioxidant. The
      antioxidant, putative cellular phospholipase inhibitor and calmodulin antagonist,
      chlorpromazine (100 microM), blocked the increase in MDA formation and after 6 hr
      decreased by 50% the degree of cell death produced by PCBC, DCVC, TFEC, and CTFC.
      Furthermore, chlorpromazine could be added 1 or 2 hr after DCVC or PCBC and still
      provide the same degree of protection. The enhanced protection with
      chlorpromazine, in relation to deferoxamine and BHT, may be related to its
      actions as a phospholipase inhibitor and/or calmodulin antagonist. These results
      show that iron-dependent lipid peroxidation plays a role in PCBC-, DCVC-, and
      CTFC-induced rabbit renal proximal tubule cell death. In contrast, iron-dependent
      lipid peroxidation plays no role in TFEC-induced proximal tubule cell death.
      These observations suggest that mechanisms other than peroxidative damage may
      predominate in the cell death produced by these four compounds.

PMID- 1987661
TI  - Gastrointestinal absorption of cadmium and metallothionein.
AB  - Intestinal uptake and transport of cadmium (Cd) to different organs were studied
      in control and oral zinc pretreated rats using an in situ intestinal loop model.
      Intestinal loop was incubated with either CdCl2 or Cd-metallothionein (Cd-MT) for
      30 and 60 min in rats under anesthesia. Induction of MT by oral Zn pretreatment
      had little effect on intestinal uptake of Cd ion. However, when intestinal loop
      was incubated with exogenous Cd-MT, the uptake of Cd was significantly smaller
      than that from CdCl2 incubation. About 50% of the Cd in the intestine of control
      rat after CdCl2 incubation was recovered in the cytosol fraction and bound to
      high-molecular-weight (greater than 60 kDa) proteins. In both Zn pretreated rats
      incubated with CdCl2 and control rats incubated with Cd-MT, Cd was mostly
      recovered in the intestinal cytosol fraction (75-85%) and was mainly bound to MT.
      After 60 min incubation of control intestinal loop with CdCl2. Cd was detected
      mainly in liver with small amounts in kidney and pancreas: with Cd-MT incubation,
      Cd was detected only in the kidney. The deposition of Cd in the liver was
      markedly decreased by Zn pretreatment. Both the uptake of Cd-MT by intestine and
      the induction of MT synthesis in the intestine by Zn pretreatment were
      demonstrated by immunohistochemistry using a specific antibody to rat liver MT.
      The results suggest a slow uptake of exogenous Cd-MT from the intestine and
      transport to kidney in contrast to deposition of Cd in the liver from CdCl2.
      Although the intracellular presence of MT does not affect the uptake of Cd from
      lumen, it may decrease both the release of Cd from the intestine and its
      deposition in liver.

PMID- 1987662
TI  - Mitochondrial dysfunction is an early event in ochratoxin A but not oosporein
      toxicity to rat renal proximal tubules.
AB  - Ochratoxin A (OA) and oosporein (OSN) are two mycotoxins that may cause
      nephrotoxicity through either mitochondrial dysfunction or lipid peroxidation.
      Using isolated rat renal proximal tubules in suspension, the cellular events
      preceding OA- or OSN-induced cytotoxicity were investigated. OA and OSN decreased
      tubule viability in a concentration (0-1 mM)- and time (0-4 hr)-dependent manner,
      with initial decreases occurring 1 hr after exposure. Tubule basal and nystatin
      stimulated oxygen consumption decreased before cell death after OA (0.5 and 1 mM)
      and 0.25 mM t-butyl hydroperoxide (TBHP) exposure, but did not decrease after OSN
      exposure (0.25-1 mM). The oxidant TBHP was used as a positive control in these
      studies. Direct probing of mitochondrial function within proximal tubules
      confirmed the toxicity of OA to mitochondria. Respiration was reduced in the
      absence and presence of a phosphate acceptor using site I (glutamate/malate) and
      site II (succinate) respiratory substrates 15 and 30 min after exposure to 1 mM
      OA. Lipid peroxidation preceded cell death after exposure to 1 mM OA and 0.25 mM
      TBHP, but did not occur after exposure to 1 mM OSN. Deferoxamine (1 mM)
      pretreatment before the addition of 1 mM OA or OSN prevented OA-induced lipid
      peroxidation, but did not prevent OA- or OSN-induced cytotoxicity. In contrast,
      deferoxamine pretreatment prevented lipid peroxidation, mitochondrial
      dysfunction, and the loss of tubule viability after exposure to 0.25 mM TBHP.
      This study shows that mitochondrial dysfunction is an early event during the
      development of OA toxicity, but not in OSN-induced toxicity. Furthermore, iron
      mediated lipid peroxidation does not contribute to OA- or OSN-induced proximal
      tubule cell death.

PMID- 1987663
TI  - Cadmium (Cd2+) disrupts intercellular junctions and actin filaments in LLC-PK1
      cells.
AB  - Studies reported in the literature suggest that cadmium (Cd2+) may disrupt the
      junctions between cells in some tissues and cell culture systems. In order to
      examine this possibility in more detail, we have studied the effects of Cd2+ on
      the integrity of intercellular junctions in the established porcine renal
      epithelial cell line, LLC-PK1. Junctional integrity was assessed by monitoring
      the collapse of domes and by measuring changes in the transepithelial electrical
      resistance in confluent cell monolayers. Exposure to Cd2+ caused a rapid decrease
      in transepithelial resistance and the concomitant collapse of domes. These
      effects occurred at Cd2+ concentrations (20-60 microM) and durations of exposure
      (as little as 1 hr) that did not alter levels of ATP or kill the cells. Electron
      microscopic studies showed that Cd2+ caused time-dependent changes in adhering
      and occluding junctional complexes, which eventually resulted in the complete
      separation of the cells. Additional studies, in which rhodamine-coupled
      phalloidin was used to visualize F-actin, showed that Cd2+ altered the structure
      of actin filaments in the cells; there was a significant reduction in the amount
      of junction-associated F-actin and in the number of stress fibers. These results
      indicate that Cd2+ has relatively specific damaging effects on the adhering and
      occluding junctions between LLC-PK1 cells and that these effects may involve the
      disruption of cytoskeletal actin filaments.

PMID- 1987664
TI  - Death and functional outcome after spontaneous intracerebral hemorrhage. A
      prospective study of 166 cases using multivariate analysis.
AB  - Using death and functional status as end points, we prospectively analyzed the
      outcome 6 months after spontaneous intracerebral hemorrhage in 166 patients
      admitted to an acute-care stroke unit on the first day of their stroke. Seventy
      one patients (43%) died, 69 (42%) had a satisfactory outcome, and 26 (16%) had a
      poor functional outcome. Early (30-day) survival was correlated with morphologic
      parameters on the initial computed tomogram (hemorrhage size, midline shift, and
      intraventricular spread of the hemorrhage), while later (6-month) survival was
      correlated with age. Using logistic regression, we found five independent
      predictors of satisfactory outcome at 6 months: age, hemorrhage size,
      intraventricular spread of the hemorrhage, limb paresis, and communication
      disorders. Of these, age was the most important predictor by far.

PMID- 1987665
TI  - Functional outcome measures in stroke rehabilitation.
AB  - I examine statistical considerations in the analysis of functional outcome
      following stroke and discuss the mathematical relation between improvement in
      function and discharge functional score. I demonstrate mathematically that the
      predictor variables of improvement and discharge functional score are the same
      and that the regression coefficients for improvement and discharge functional
      score will be equal, except for the admission functional score, for which a
      mathematically defined relation exists. I argue that the relation between
      admission functional score and discharge functional score must be positive and
      strong and that the relation between admission functional score and improvement
      must be negative for the stroke population. I believe that an ignorance of
      statistical concepts, especially confounding, and of the differences between raw
      correlations, partial correlations, and predictors have led to much confusion in
      functional outcome research.

PMID- 1987666
TI  - Cerebrovascular disease in Ehlers-Danlos syndrome.

PMID- 1987667
TI  - Activation of coagulation in acute cardioembolic stroke.
AB  - The hematologic disorders in patients with acute cardioembolic stroke are not
      fully understood, and no reliable measures are available to identify patients at
      high risk for recurrent embolism. We analyzed coagulation and fibrinolytic
      functions in 22 patients with cardiogenic cerebral embolism less than or equal to
      24 hours after onset and in 25 age-matched controls. The levels of antithrombin
      III, protein C, and alpha 2-plasmin inhibitor were significantly lower in the
      patients than in the controls (p less than 0.001, 0.02, and 0.05, respectively).
      In contrast, the plasma concentrations of thrombin-antithrombin III complex and
      crosslinked D-dimer were markedly higher in the patients than in the controls (p
      less than 0.01 and 0.001, respectively). At the time of admission, the plasma
      concentrations of thrombin-antithrombin III complex and crosslinked D-dimer in
      the eight patients at high risk for recurrent embolization (one with prodromal
      embolism, three with intracardiac thrombi, and four with recurrent embolization)
      were 2.8 and 3.5 times, respectively, higher than those in the 14 patients
      without recurrence or thrombus formation. The lowest concentration of crosslinked
      D-dimer in the eight patients at high risk for recurrent embolization was 600
      ng/ml on admission. Our results suggest that patients with acute cardioembolic
      stroke have various degrees of consumption coagulopathy and that the plasma
      concentrations of thrombin-antithrombin III complex and crosslinked D-dimer can
      be useful indicators of those who are prone to recurrent embolization during this
      stage.

PMID- 1987668
TI  - Platelet volume, aggregation, and adenosine triphosphate release in cerebral
      thrombosis.
AB  - We compared whole blood platelet aggregation, adenosine triphosphate release,
      platelet count, platelet crit (percentage volume of platelets), and mean platelet
      volume during the acute, subacute, and chronic periods of cerebral thrombosis in
      22 patients with value in 29 controls. During the acute and subacute periods,
      platelet aggregation, platelet count, platelet crit, and mean platelet volume
      were significantly less in the patients than in the controls (p less than 0.05
      0.01) while the adenosine triphosphate release rate per volume of platelets was
      significantly greater (p less than 0.05). During the acute period, infarct size
      showed a significant positive correlation with platelet aggregation (r = 0.59, p
      less than 0.01) and adenosine triphosphate release rate (r = 0.70, p less than
      0.001) but a negative correlation with platelet count (r = -0.44, p less than
      0.05). Our results suggest that platelet aggregation is reduced during the acute
      period due to the consumption of platelets during thrombogenesis but that the
      remaining individual platelets are hyperactive. Platelet consumption during the
      acute period increases with infarct size. During the chronic period, platelet
      crit and mean platelet volume were significantly less in the patients than in the
      controls (p less than 0.01) while the adenosine triphosphate release rate was
      significantly greater (p less than 0.01), suggesting sustained platelet
      consumption and chronically enhanced secretion of individual platelets.

PMID- 1987669
TI  - Middle cerebral artery blood velocity and cerebral blood flow in sickle cell
      disease.
AB  - To understand better the relationship between blood velocity measured by
      transcranial Doppler and cerebral blood flow measured by the 133Xe inhalation
      method, we examined 23 patients undergoing evaluation in the Comprehensive Sickle
      Cell Center at Columbia University. Blood velocity in the middle cerebral artery
      was directly related to cerebral flow (r = 0.77; p less than 0.05). A
      multivariate analysis in this sample made it possible to improve this correlation
      to account for more than 90% of the variability in cerebral blood flow by the use
      of transcranial Doppler measures of velocity and pulsatility along with the
      patient's age and hematocrit (r = 0.95; p less than 0.001). It is likely that the
      combination of Doppler and clinical or demographic variables in other diseases
      will similarly improve the quantitative estimation of cerebral blood flow.

PMID- 1987670
TI  - Noninvasive assessment of cerebral collateral blood supply through the ophthalmic
      artery.
AB  - We assessed the potential of 2-MHz pulsed-wave transorbital Doppler
      ultrasonography to delineate the role of the ophthalmic artery as a source of
      collateral cerebral blood supply by comparing oculopneumoplethysmography,
      transorbital Doppler ultrasonography, periorbital continuous-wave Doppler
      ultrasonography, and transcranial Doppler ultrasonography in 25 patients with
      unilateral internal carotid artery occlusion and five controls with 10 normal
      internal carotid arteries. Systolic ophthalmic artery blood velocity was reduced
      ipsilateral to an internal carotid artery occlusion (38.2 +/- 10.2 cm/sec)
      compared with the contralateral and control velocities (46.0 +/- 10.3 and 47.5 +/
      6.8 cm/sec, respectively; p less than 0.05). Ophthalmic systolic pressure
      measured by oculopneumoplethysmography was 94.7 +/- 13.2 mm Hg ipsilateral to an
      internal carotid artery occlusion compared with 108.4 +/- 15.3 mm Hg on the
      contralateral side (p less than 0.01). Transorbital and periorbital Doppler
      ultrasonography detected reversed ophthalmic artery blood flow ipsilateral to an
      internal carotid artery occlusion in 44.0% and 40.0% of the patients,
      respectively. Systolic middle cerebral artery blood velocity was 55.2 +/- 22.3
      cm/sec ipsilateral to an internal carotid artery occlusion compared with 79.4 +/-
      23.5 cm/sec on the contralateral side (p less than 0.05) and 101.2 +/- 18.9
      cm/sec in the controls (p less than 0.05). Reversed ophthalmic artery blood flow
      was associated with a low middle cerebral artery blood velocity and lack of major
      intracerebral collaterals. Transorbital Doppler ultrasonography permits
      noninvasive evaluation of the ophthalmic artery.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1987671
TI  - Mild hypothermic intervention after graded ischemic stress in rats.
AB  - We investigated the effect of mild (34 degrees C) postischemic hypothermia on
      hippocampal neuronal damage in 43 rats as a function of the duration of forebrain
      ischemia. Two temperatures and two durations were investigated. In two
      normothermic groups ischemia lasted 8 (n = 15) and 12 (n = 10) minutes,
      respectively. In two hypothermic groups ischemia lasted 8 (n = 9) and 12 (n = 9)
      minutes, respectively, and was followed immediately by the lowering and
      maintenance of rectal temperature to 34 degrees C for 2 hours. Seven days after
      the ischemic insult, the rats were sacrificed and the brains were prepared for
      histologic analysis; the percentage of necrotic neurons among the total neuronal
      population in selected CA1/2 sectors of the hippocampus was determined. There was
      a significant decrease in the percentage of necrotic neurons in the central
      (77.5% versus 55.5%, p = 0.006) and lateral (62.5% versus 38.9%, p=0.005) areas
      and in the overall CA1/2 sector of the hippocampus (71.8% versus 52.2%, p =
      0.008) for the 8-minute hypothermic group compared with the 8-minute normothermic
      group. In contrast, no differences were detected in any area of the hippocampus
      between the 12-minute normothermic and the 12-minute hypothermic groups (p = 0.29
      0.49). Our data indicate that mild postischemic whole-body hypothermia
      ameliorates neuronal survival when ischemia lasts 8 minutes but not 12 minutes.

PMID- 1987672
TI  - The role of neutrophils and platelets in a rabbit model of thromboembolic stroke.
AB  - Cerebral ischemia is accompanied by many of the cardinal features of acute
      inflammation such as neutrophil and platelet activation and accumulation. We
      sought to determine whether circulating neutrophils or platelets contribute to
      brain injury in a rabbit model of thromboembolic stroke that includes a fixed
      duration of superimposed systemic hypotension. We randomized 18 rabbits to
      receive either antineutrophil antiserum (n = 6), antiplatelet antiserum (n = 5),
      or nonimmune serum (n = 7). We assessed brain ischemia by measuring cerebral
      blood flow, intracranial pressure, and infarct size. Following the intracarotid
      administration of an autologous clot, cerebral blood flow in all groups fell to
      less than 5 ml/100 g/min during induced hypotension. After restoration of
      baseline blood pressure, mean cerebral blood flow in neutropenic animals
      recovered to 20-30 ml/100 g/min while that in control and thrombocytopenic
      rabbits remained at less than 10 ml/100 g/min. Intracranial pressure in control
      animals rose steadily to a final value of 241% of baseline, while a much smaller
      increase (148% of baseline) was noted in the thrombocytopenic group; no change
      from baseline was evident in the neutropenic group. Infarct size was
      significantly (p less than 0.05) reduced in the neutropenic group but not in the
      thrombocytopenic group. These results suggest that neutrophils may be important
      contributors to ischemia-induced brain injury whereas the role of platelets is
      more subtle.

PMID- 1987673
TI  - Attenuated neuropathology by nilvadipine after middle cerebral artery occlusion
      in rats.
AB  - We investigated the effects of nilvadipine, a calcium antagonist, on cerebral
      ischemia in rats. Under halothane anesthesia, 30 rats had a 3-0 nylon suture
      introduced through the extracranial internal carotid artery to occlude the left
      middle cerebral artery. Nilvadipine was dissolved in polyethylene glycol 400.
      Immediately following occlusion, group 1 rats (n = 10) were treated
      subcutaneously with vehicle and group 2 and 3 rats were treated with 1.0 (n = 10)
      and 3.2 (n = 10) mg/kg nilvadipine, respectively. Perfusion fixation was
      performed 24 hours later, and the histopathologic outcomes were quantified. In
      group 1 infarct volume was 28.2 +/- 11.4% of the total cerebral volume; in groups
      2 and 3 infarct volumes were 25.5 +/- 11.6% (NS) and 13.9 +/- 9.2% (p less than
      0.05 different from group 1), respectively. Nilvadipine decreased ischemic
      neuronal injury in a dose-dependent manner and may be of use in the treatment of
      cerebral ischemia.

PMID- 1987674
TI  - Effects of prostaglandin F2 alpha and thromboxane A2 analogue on bovine cerebral
      arterial tone and calcium fluxes.
AB  - We determined sources of activator calcium for prostanoid-induced cerebrovascular
      constriction by measuring isometric tension and calcium-45 (45Ca) fluxes in
      bovine middle cerebral arteries. Constriction induced by prostaglandin F2 alpha
      or the stable thromboxane A2 analogue SQ-26,655 was near-maximally inhibited in
      calcium-deficient solutions but only partially inhibited by calcium antagonists
      (10(-5) M verapamil or 3.3 x 10(-7) M nifedipine). Studies of 45Ca binding at
      different external Ca2+ concentrations showed that cerebral arteries possess two
      calcium binding sites, a high-affinity site and a low-affinity site. Each
      prostanoid significantly increased low-affinity 45Ca uptake (external Ca2+
      concentration = 1.2 mmol/l) during 5 minutes of 45Ca loading; for prostaglandin
      F2 alpha 45Ca uptake increased from 69 to 108 nmol/g and for SQ-26,655, from 78
      to 141 nmol/g. The prostanoid-induced increases in low-affinity 45Ca uptake were
      completely abolished by pretreatment with verapamil or nifedipine. Prostaglandin
      F2 alpha, SQ-26,655, verapamil, and nifedipine had no effect on high-affinity
      45Ca uptake (external Ca2+ concentration = 45 mumol/l) or 45Ca efflux (after 60
      minutes' preincubation in calcium-deficient media). Prostaglandin F2 alpha and SQ
      26,655 each appear to constrict cerebral arteries by two mechanisms: first, by
      promoting calcium uptake from low-affinity binding sites through receptor
      operated channels sensitive to the calcium antagonists, and second, by releasing
      calcium from depletable internal stores.

PMID- 1987676
TI  - Cerebral infarction in patients with nephrotic syndrome.
AB  - We describe two adult patients who presented with acute cerebral infarction and
      were found to have a hypercoagulable state due to nephrotic syndrome. One patient
      had a deficiency of free protein-S. The other patient had a pulmonary embolus 4
      months after the stroke. Our cases demonstrate that the hypercoagulable state
      associated with nephrotic syndrome can be associated with cerebral arterial
      thrombosis and infarction in adults. Examination of the urine remains an
      important part of the evaluation of patients with recent stroke. The presence of
      severe proteinuria and a low serum albumin content should prompt consideration of
      a hypercoagulable state. Our experience suggests that anticoagulant drugs may be
      required to reduce the risk of new thrombotic events.

PMID- 1987675
TI  - Hypertension, cigarette smoking, and the decline in stroke incidence in eastern
      Finland.
AB  - Finland has high rates of both cardiovascular disease and cardiovascular disease
      risk factors. We studied random samples of the population 30-59 years of age for
      risk factors in two provinces of eastern Finland in 1972 and 1977. We then
      followed both cohorts until 1985 through linkage with national hospital discharge
      and death certificate registers. The prevalence of hypertension and smoking in
      both provinces declined between 1972 and 1977, as did the stroke incidence in the
      8-year period of follow-up of each cohort. We observed no differences in stroke
      incidence between the two provinces. The relative risk of stroke in the later
      period (1977-1985) was 0.71 and 0.58 for men and women, respectively, when
      compared with the earlier period (1972-1980). Overall, 28% of all stroke events
      could be attributed to hypertension, 17% to smoking, and 43% to these two factors
      jointly. The decrease in the prevalence of hypertension and smoking accounted for
      about 29% of the decline.

PMID- 1987677
TI  - Recurrent transient ischemic attacks and stroke in association with an internal
      carotid artery web.
AB  - Fibromuscular dysplasia is a nonatherosclerotic vascular disease that most
      commonly affects cervical carotid arteries at the C1-C2 level when cephalic
      arteries are involved. Several histopathologic and angiographic subtypes of
      fibromuscular dysplasia exist; most have a benign natural history. We describe
      the third reported case of a pathologically proven, symptomatic proximal internal
      carotid artery web and suggest that patients with this lesion are at a higher
      risk for stroke.

PMID- 1987678
TI  - The Willis lecture: transient ischemic attacks, scientific method, and new
      realities.
AB  - First described by Thomas Willis in 1679 and defined in the 1950s, transient
      ischemic attack is universally agreed to be an episode of focal neurologic
      deficit in a vascular distribution, sudden in onset and resolving without
      residual deficit in less than or equal to 24 hours. Transient ischemic attack is
      diagnosed by characteristic history and absence of residua on neurologic
      examination. After these criteria had been accepted, regional cerebral blood flow
      and computed cranial tomography in the 1970s, later positron emission tomography,
      and even more recently, magnetic resonance imaging reveal prolonged
      pathophysiologic and metabolic disturbances even in persons with all the
      definitional characteristics of transient ischemic attack. These persistent
      abnormalities necessitate reexamination of the validity of the concept of
      transient ischemic attack. Furthermore, our group suspects that transient
      ischemic attack is probably only a marker, and not itself the risk factor, for
      the cerebral infarction which frequently follows transient ischemic attack.
      Additionally, the surprising frequency with which cerebral infarction,
      unrecognized by patient or physician, is revealed using neuroimaging techniques
      has created a need to redefine the categories heretofore used for diagnosis and
      assessment of therapy and prognosis for transient ischemic attack and cerebral
      infarction.

PMID- 1987679
TI  - Transplantation timeline. Mankind's three millennia--one maverick's three decades
      in the struggle against biochemical individuality.

PMID- 1987680
TI  - Long-term outlook for renal transplant recipients with one-year function.
      "Doctor, what are my chances"?
AB  - Patients with renal transplants that survive the first year often ask about the
      chance of long-term function. We studied 1850 patients with primary transplants
      from June 7, 1963 to September 1, 1988 who had graft survival of greater than 1
      year. Patients were grouped by donor type, diabetic status, and whether or not
      they received cyclosporine (CsA). Half-life (T1/2) was used to compare long-term
      survival rates. We determined the long-term graft survival inclusive and
      exclusive of death with function (DwF) in order to study all patients and to
      direct attention to immunologic losses. Pre-CsA, DwF was the major cause of graft
      loss in each cohort. Cause of DwF was cardiovascular (49%), infection (26%), and
      cancer (14%). The percentage of patients experiencing DwF was much higher in the
      pre-CsA group vs. the CsA group: HLA-identical living related donor, 16% vs. 3%;
      non-HLA-identical LRD, 22% vs. 5%; and cadaver donors, 26% vs. 11%. T1/2 for 711
      transplants to diabetics (DM) was 9.01 +/- .54 years, while for transplants to
      1139 nondiabetics (NDM) T1/2 was 13.57 +/- .68 (P less than .05). When DwF is
      excluded (DwFex) DM T1/2 = 23.5 +/- 2.69 and NDM T1/2 = 22.2 +/- 1.55 (NS).
      Overall, for HLA-identical transplants (n = 297) T1/2 = 26.13 +/- 3.35 and DwFex
      T1/2 = 104.3 +/- 28.93. Nonidentical LRD (n = 845) T1/2 = 11.25 +/- .61 and DwFex
      T1/2 = 19.37 +/- 1.55. For CAD (n = 701) T1/2 = 9.10 +/- .54 and DwFex T1/2 =
      17.49 +/- 1.65. Comparing pre- and post-CsA cohorts, CsA has not resulted in
      significant improvement in long-term graft survival by T1/2 analysis with DwFex.
      It appears that overall long-term graft survival has improved with the
      introduction of CsA. Much of the improvement may be attributed to better first
      year graft survival and a reduction in cases of DwF. DM patients have an equal
      opportunity for long-term graft survival if they do not die from other causes.
      Excluding DwF, especially as an older population is transplanted, is important in
      determining chances of immunologic loss. Use of this type of analysis suggests
      that long-term outlook for 1-year graft survivors is excellent.

PMID- 1987682
TI  - The use of "marginal" donors for organ transplantation. The influence of donor
      age on outcome.
AB  - The influence of donor age on outcome was studied in the recipients of 12,131
      cadaveric renal allografts, 3026 heart allografts, and 2913 liver allografts with
      followup information in the UNOS data base for transplants performed between
      10/1/87 and 12/31/89. For recipients of kidney transplants, donors of ages 6-15
      had significantly better 1-year graft survival than donors of ages 56-65, but the
      difference was only 7.0%. Donors of age greater than 65 actually did better than
      donors ages 56-65, but donors less than or equal to 5 were less satisfactory.
      Kidneys from older donors survived as well as kidneys from younger donors in
      patients with repeat transplants, diabetes, black race, age over 45, O HLA or 5
      and 6 HLA matches, delayed graft function, shared kidneys and PRA greater than
      50. For kidney recipients, multifactorial analysis by Cox regression showed that
      donor age was less important than the use of ALG, donor race, diabetes or peak
      PRA in ages 16-45, delayed function, repeat transplant, and HLA match. Recipients
      of heart transplants from donors ages 45-55 had 1-year graft survival that was
      8.4% less than recipients of hearts from donors age 16-45. However, 32.7% of
      heart patients died during the first 12 months after listing without benefit of a
      transplant. Liver transplant recipients of donor ages 16-45 had 10.8% better 1
      year graft survival than recipients of donors greater than 45, but a greater
      percentage of older donors were transplanted to high risk and older recipients.
      Tragically, 24.3% of patients listed for liver transplantation died within 12
      months without a transplant. This analysis shows that satisfactory graft survival
      can be achieved using older donors and that age in itself should not be a barrier
      to organ donation, providing that organ function is normal and that specific
      disease of the organ is absent.

PMID- 1987681
TI  - The liver transplant waiting list--a single-center analysis.
AB  - At this transplant center 1340 patients were entered on the liver transplant
      waiting list during the first 25 months (October 1987 to November 1989) after the
      initiation of the UNOS allocation system for liver grafts. Of these 972 (72.5%)
      of the patients received a graft, 120 (9.0%) died waiting for a graft, 109 (8.1%)
      remained on the active list as of the study endpoint of December 15, 1989, 123
      (9.2%) were withdrawn from candidacy, and 16 (1.2%) received a transplant at
      another center. A total of 1201 patients were candidates for a first graft. Of
      the 812 primary candidates who received a graft, 64.8% received their graft
      within one month of entry on the waiting list. Of the 109 primary candidates who
      died before a graft could be found, 79.0% died within a month of entry onto the
      waiting list. At time of transplantation, 135 (16.6%) primary recipients of a
      graft were UNOS class 1, 326 (40.1%) were UNOS class 2, 190 (23.4%) were UNOS
      class 3, and 161 (19.8%) were UNOS class 4. Actuarial survival rates (percentage)
      at 6 months for recipients in UNOS class 1, class 2, class 3, and class 4 were
      88.7 +/- 2.9, 82.6 +/- 2.1, 78.4 +/- 3.2, and 68.4 +/- 3.9, respectively (P less
      than 0.001). At the time of death of recipients who failed to get a graft, 6
      (5.5%) were UNOS class 1, 14 (12.8%) were UNOS class 2, 23 (21.1%) were UNOS
      class 3, and 66 (60.6%) were UNOS class 4. These results indicate that a high
      proportion of liver transplant candidates are in urgent need of a graft and that
      the UNOS system succeeds in giving these patients high priority. However patient
      mortality on the waiting list and after transplantation would lessen
      significantly if more patients with end-stage liver disease were referred to the
      transplant center in a timely manner before their condition reaches the point
      where the probability of survival is diminished.

PMID- 1987683
TI  - Estimation and characterization of the potential renal organ donor pool in
      Pennsylvania. Report of the Pennsylvania Statewide Donor Study.
AB  - The Pennsylvania Statewide Donor Study evaluated deaths under the age of 66
      occurring in 149 participating hospitals in 1987. After elimination of 6146
      patients from 11,983 based upon ICD-9 code criteria, an on-site medical record
      review was performed on 5603 patients. Each patient was assessed for organ donor
      suitability based upon brain death and medical suitability criteria--and, after a
      series of eliminations, 453 patients were found to have a moderate or higher
      potential as acceptable organ donors. An estimation of the organ donor rate was
      placed between 38.3 and 55.2 donors per million population per year, depending
      upon the stringency of organ donor criteria. Educational efforts targeted at
      physicians, patient's families and transplant surgeons will be necessary,
      however, to attain this maximal rate.

PMID- 1987684
TI  - Evidence that combined procurement of pancreas and liver grafts does not affect
      transplant outcome.
AB  - We compared outcome after pancreas and liver transplantation when both organs
      were retrieved from the same donor to outcome when only one or the other organ
      was retrieved. A total of 166 cadaver pancreata were transplanted at our
      institution between November 1984 and August 1989; 64 were obtained from donors
      in whom the liver was also donated (LD), and 102 were retrieved from non-liver
      donors (non-LD). Of the 64 LD pancreata, 53 were the entire organ with a segment
      of duodenum and 11 were segmental. Both the superior mesenteric artery (SMA) and
      celiac axis (CA) were retained with the pancreas in 13, while in 40 pancreata the
      CA was retrieved with the liver and the blood supply to the pancreas was
      reconstructed [end-to-side anastomosis of splenic artery (SA) to SMA in 11 and a
      Y-graft of donor iliac bifurcation to SA and SMA in 29]; a graft of common iliac
      vein was used to extend the portal vein in 10. The technical failure rate was
      8/64 (12%) in LD pancreata, and 13/102 (13%) in non-LD pancreata (P greater than
      0.1). The overall pancreas allograft survival rate at 1 year was 76% for
      pancreata obtained from LD (n = 64) and 64% for technically successful
      transplanted pancreata obtained from non-LD (n = 102, P greater than 0.1). One
      year actuarial patient survival was 95% in the LD group and 90% in the non-LD
      group (P greater than 0.1). Among the 64 livers from pancreas donors (PD), 20
      were transplanted at our hospital, 42 were transported to other institutions, and
      2 were not transplanted. Follow-up information regarding 47 primary orthotopic
      adult, whole liver PD recipients (18 at our hospital, 29 at other institutions)
      was available for analysis and was compared with information concerning 62 adult
      recipients of primary orthotopic whole livers from non-PD transplanted during the
      same period at our institution. The total PNF rate among 47 PD liver allografts
      was 2/47 (4%), compared with 1/62 (1%) for the livers from non-PD (P greater than
      0.1). The technical failure rate for the PD group was 1/47 (2%) versus 5/62 (8%)
      in the non-PD group (P greater than 0.1). The overall liver allograft survival
      rate at 1 year was 75% for livers obtained from PD (n = 47) and 81% for livers
      obtained from non-PD (n = 62, P greater than 0.1). One-year actuarial patient
      survival was 88% in the PD group and 81% in the non-PD group (P greater than
      0.1). We concluded that simultaneous procurement of liver and pancreas grafts had
      no significant detrimental effect on the rate of technical failure, or on
      allograft or patient survival after either pancreas or liver transplantation.

PMID- 1987685
TI  - The predictive value of donor liver biopsies for the development of primary
      nonfunction after orthotopic liver transplantation.
AB  - Methods of accurately assessing the suitability of donor livers prior to
      transplantation are required if the incidence of primary nonfunction (PNF) is to
      be reduced. This study evaluated the ability of donor liver biopsies to predict
      the development of primary nonfunction after transplantation. From June 1987
      until May 1990, 170 liver transplants were performed in 147 patients. A total of
      124 donor liver biopsies were obtained and divided into three groups. Group 1
      biopsies (n = 77) were obtained after revascularization of the liver, group 2
      biopsies (n = 19) were obtained prior to donor hepatectomy but examined only
      after implantation, and group 3 biopsies (n = 28) were obtained as in group 2,
      but were examined prior to implantation. Three of 89 (3.4%) livers interpreted as
      having normal histology developed primary nonfunction, while one of 26 (3.8%)
      biopsies interpreted as having a minimal or moderate amount of fatty infiltration
      developed primary nonfunction. PNF occurred in 7 of 8 livers with severe fatty
      infiltration (3), hydropic degeneration (3), and centrilobular necrosis (1). A
      fourth liver with hydropic degeneration and poor function ultimately failed
      requiring retransplantation 8 weeks later. Analysis of liver function revealed
      progressive elevation in aspartate-aminotransferase, alanine-aminotransferase,
      lactate dehydrogenase, and serum ammonia (NH3) with increasing degrees of fatty
      infiltration. Donor age and weight was also found to be significantly higher in
      livers with fatty infiltration. This study suggests that donor liver biopsies
      demonstrating normal histology or minimal-to-moderate fatty infiltration function
      adequately, but that donor livers with severe fatty infiltration or hydropic
      degeneration function poorly and should not be transplanted.

PMID- 1987688
TI  - Similarity of pulmonary rejection patterns among heart-lung and double-lung
      transplant recipients.
AB  - The transbronchial biopsy and clinical courses of 9 double-lung and 1 single-lung
      recipients surviving greater than 10 days were analyzed and compared to those of
      15 heart-lung transplants performed during the same time period. Of these, 8
      isolated lung (LT) and 11 heart-lung transplant (HLT) recipients survived greater
      than 50 days and were at risk of developing obliterative bronchiolitis believed
      to be a form of chronic rejection. Cyclosporine-based immunosuppression, in
      combination with azathioprine and steroids, was used for 22 of 25 patients. Two
      double-lung recipients and 1 heart-lung patient received FK506 as the sole
      immunosuppressive agent; 90% and 62% of LT, and 67% and 54% of HLT recipients
      developed acute and chronic rejection, respectively (P = NS). The average time to
      first episode of acute (30.2 days [LT] versus 21.5 days [HLT]) and chronic
      rejection (146 days [LT] versus 193.7 days [HLT]) was not different between
      groups (P = NS). Age (34.2 [LT] versus 29.1 [HLT]) and sex (M:F, 5:5 [LT] versus
      5:10 [HLT]) were also not found to be discriminators. The histologic diagnosis of
      chronic rejection was associated with significant declines in FEV1.0 and FEF25-75
      (P less than 0.02). There was only one instance of cardiac rejection among the
      heart-lung transplant recipients. Heart-lung and isolated lung transplant
      patients appear to be at similar risk for developing acute or chronic pulmonary
      rejection.

PMID- 1987687
TI  - Sequential determinations of serum interleukin 6 levels as an immunodiagnostic
      tool to differentiate rejection from nephrotoxicity in renal allograft
      recipients.
AB  - Serum interleukin 6 (IL-6) levels were utilized as an immunologic marker of
      activation of T cells and macrophages in renal allograft recipients treated with
      a cyclosporine and prednisone immunosuppressive regimen. IL-6 concentrations were
      estimated in serum samples selected to correspond to similar timepoints in the
      clinical courses of renal transplant recipients suffering four types of events:
      group I, quiescent patients without rejection or infectious disease (n = 16, 147
      samples); group II, patients with only rejection episodes (n = 26, 291 samples);
      group III, patients with only infectious episodes (n = 10, 87 samples); and group
      IV, patients with CsA-induced nephrotoxicity (n = 15, 117 samples). Serum IL-6
      activity measured using an IL-6-dependent cell line (MH60.BSF-2) was specific for
      this lymphokine based upon the capacity of monoclonal anti-IL-6 antibodies to
      block target cell proliferation. The control group displayed uniformly elevated
      IL-6 levels during the first posttransplant day (mean 20.1 +/- 4.1 U/ml range 6.4
      64 U/ml), thereafter decreasing by 10-14 days to a mean level of 3.4 +/- 0.9 U/ml
      (range 1.0-4.2 U/ml). The rejection group showed increased IL-6 levels ranging
      from 5.3 +/- 0.4 U/ml (range 1.0-64 U/ml) to 56.2 +/- 13.3 U/ml (range 10-300
      U/ml, P less than 0.01), occurring at a mean of 2 days (range 0-10 days) before
      the diagnosis of rejection was established by clinical criteria. Interestingly,
      all three recipients treated with OKT3 and 5/11 treated with antilymphocyte
      globulin displayed further significant increases in serum IL-6 levels (OKT3: 46.0
      +/- 12.9 U/ml; ALG: 34.6 +/- 7.8 U/ml) one day after inception of treatment. Five
      of 10 recipients displaying septic events showed elevated serum IL-6 activity-
      namely, 5.0 +/- 1.2 U/ml to 47.5 +/- 16.2 U/ml, beginning at a mean of 1.2 days
      before diagnosis. Contrariwise, recipients afflicted with CsA-induced
      nephrotoxicity displayed reduced IL-6 levels (mean = 1.4 +/- 0.18 U/ml). The
      ratio (IL-6 activity/CsA trough level) proved to be even more useful than the
      serum IL-6 level itself to discriminate acute rejection from nephrotoxicity-
      namely, 0.53 versus 0.006, respectively (P less than 0.01).

PMID- 1987686
TI  - The clinical significance of the arterial ketone body ratio as an early indicator
      of graft viability in human liver transplantation.
AB  - Arterial ketone body ratio (AKBR) was measured sequentially in 84 liver
      transplantations (OLTx). These transplantation procedures were classified into 3
      groups with respect to graft survival and patient condition at the end of the
      first month (Group A, the grafts survived longer than 1 month with satisfactory
      patient condition; Group B, the grafts survived longer than 1 month but the
      patients were ICU-bound; Group C, the grafts were lost and the patients died or
      underwent re-OLTx). In Group A, the AKBR was elevated to above 1.0 by the second
      postoperative day. In Group B, the AKBR was elevated to above 0.7 but stayed
      below 1.0 during this period. In Group C, the AKBR remained below 0.7 longer than
      2 days after operation. Although conventional liver function tests showed
      significant increases in Groups B and C as compared with Group A, they were less
      specific in predicting ultimate graft survival.

PMID- 1987689
TI  - The progression of mild acute cardiac rejection evaluated by risk factor
      analysis. The impact of maintenance steroids and serum creatinine.
AB  - The natural course of mild acute cardiac allograft rejection (MAR) under
      cyclosporine-based therapy is generally considered benign, and usually
      antirejection therapy is not instituted. The present study was undertaken to
      determine the frequency of and the risk factors for progression of MAR into a
      clinically significant (moderate or severe) rejection on subsequent
      endomyocardial biopsy (EMB). Among 167 cardiac recipients, transplanted from
      3/1984 to 4/1990, MAR under cyclosporine-based therapy was diagnosed on 220 EMBs.
      Depending upon the outcome on the subsequent EMB, MAR was categorized as
      progressive or nonprogressive. This served as the dependent variable for a
      stepwise logistic regression analysis evaluating 11 covariates as potential risk
      factors: perioperative antibody prophylaxis (ATG vs. OKT3), maintenance therapy,
      underlying disease, HLA-mismatches for A- and B + DR-loci, serum creatinine
      (mg/dl) and cyclosporine HPLC blood level (ng/ml) at diagnosis of MAR and at
      subsequent biopsy, recipient age, donor age. 40 (18.2%) of 220 MARs became
      progressive as opposed to 37 (7.3%) of a control cohort of 507 negative EMBs (P
      less than 0.0001). Stepwise logistic regression yielded the type of maintenance
      therapy (P = 0.0019) and serum creatinine level at diagnosis of MAR (P = 0.0615)
      as independent predictors of progression of MAR. After adjustment for influence
      of maintenance therapy and serum creatinine none of the cyclosporine variables
      provided any additional information. MARs without maintenance steroids and low
      serum creatinine levels had the highest risk (37.2% observed incidence) to
      develop moderate or severe rejection on subsequent EMB. This analysis supports
      evidence that diagnosis of MAR on EMB is associated with a considerable high
      progression rate into clinically significant rejection when compared to negative
      EMBs. Progression particularly occurs in MAR under steroid-free maintenance
      therapy and suggests early augmentation of immunosuppression. In terms of
      progression of MAR serum creatinine values, obviously indicating cyclosporine
      nephrotoxicity, appear to reflect the extent of cyclosporine-mediated
      immunosuppressive activity more properly than parameters of its bioavailability
      by measuring cyclosporine HPLC blood levels.

PMID- 1987690
TI  - Cyclosporine's effect on functional reserve in the renal allograft.
AB  - Thirteen renal allograft recipients (6 patients on cyclosporine/7 patients on
      azathioprine) participated in a short-term oral protein-loading study to
      determine the effect of cyclosporine on an allograft's functional reserve. The
      baseline glomerular filtration rate of the two groups were similar (52 +/- 18
      ml/min/1.73 m2 for the azathioprine/conventional therapy (CT) group and 47 +/- 12
      ml/min/1.73 m2 for the cyclosporine (CsA) group), as were the baseline effective
      renal plasma flows (218 +/- 78 ml/min/1.73 m2 and 222 +/- 75 ml/min/1.73 m2,
      respectively). At 3 hr following the protein load there was an increase in GFR to
      66 +/- 28 ml/min/1.73 m2 in the CT group. The GFR (39 +/- 8 ml/min/1.73 m2) of
      the CsA group at this time was unchanged. The responses in ERPF were similar. No
      significant difference was found between the two groups baseline RAA profiles
      (4.7 +/- 3.3 ng/ml/hr (CT) and 4.7 +/- 1.7 ng/ml/hr [CsA]), or those at the third
      hour (8.1 +/- 8.3 ng/ml/hr (CT) and 3.5 +/- 1.9 ng/ml/hr [CsA]). The data in this
      study indicate that CsA alters the renal allograft's response to a protein meal.
      This difference may be related to an altered vasodilatory response. This altered
      vascular reactivity may be mediated through renin activation and/or other
      hemodynamic regulators such as prostaglandins.

PMID- 1987691
TI  - Rapamycin, a potent immunosuppressive drug for vascularized heart, kidney, and
      small bowel transplantation in the rat.
AB  - The effectiveness of rapamycin (RAPA) was examined for heart, kidney, and small
      bowel allografts in rats. Untreated or vehicle only-infused Wistar Furth (RT1u)
      recipients rejected Buffalo (RT1b) heart allografts within a mean survival time
      (MST) of 6.5 +/- 0.5 and 6.3 +/- 0.5 days, respectively. In contrast, a 14-day
      continuous intravenous (i.v.) infusion by an osmotic pump of 0.08 mg/kg/day RAPA
      to WFu recipients prolonged BUF heart allograft survival to an MST of 34.4 +/-
      12.1 days (P = 0.0001). There was a graded dose-response to 0.16 mg/kg (39.0 +/-
      8.7 days; P = 0.0001), 0.32 mg/kg (55.7 +/- 3.3 days; P = 0.0001) and 0.8 mg/kg
      (48.0 +/- 3.6; P = 0.0001). Furthermore, intraarterial/intragraft but not i.v.
      infusion of 0.02 mg/kg/day prolonged BUF heart allografts--namely, an MST of 14.6
      +/- 1.4 days versus 8.6 +/- 2.6 days (P = 0.0001), respectively. Local delivery
      doses of RAPA were about as effective as the same dose delivered i.v.: 0.08 mg/kg
      MST 37.0 +/- 18.3 days (P = 0.0001); 0.32 mg/kg, 40.0 +/- 3.9 days (P = 0.0001);
      and 0.8 mg/kg, 54.8 +/- 8.2 days (P = 0.0001). Systemic i.v. RAPA therapy with
      0.08 or 0.8 mg/kg/day prolonged the survival of BUF kidney grafts in WFu
      recipients--namely, an MST of 52.7 +/- 42.7 (NS) and 90.2 +/- 62.4 (P = 0.001)
      days, respectively, versus an MST of 11.6 +/- 1.5 days in control WFu recipients
      only infused with vehicle. While normal WFu rats reject heterotopic BUF small
      bowel allografts within an MST of 10.0 days, a 14-day course of i.v. RAPA
      treatment significantly (P = 0.0001) prolonged small bowel allograft survival to
      an MST of 26.8 +/- 3.7 days.

PMID- 1987692
TI  - Synergistic interactions of cyclosporine and rapamycin to inhibit immune
      performances of normal human peripheral blood lymphocytes in vitro.
AB  - Rapamycin, an actinomycete macrolide lactone that inhibits cytokine-induced
      immunoactivation, and cyclosporine, an endecapeptide that prevents transcription
      of lymphokine messenger RNA, display mutually synergistic interactions in vitro
      and in vivo. Using the rigorous median-effect analysis to dissect the nature of
      immunosuppressive drug interactions, rapamycin significantly augmented the
      inhibitory effects of cyclosporine and/or dexamethasone upon human peripheral
      blood lymphocyte activation by phytohemagglutinin, anti-CD3 monoclonal antibody,
      and mixed lymphocyte reaction. Furthermore, the addition of rapamycin potentiated
      the activity of cyclosporine to reduce cytotoxic cell generation and precursor
      frequency during in vitro alloactivation, using cell-mediated lympholysis and
      limiting dilution analyses, respectively. Similarly, cyclosporine potentiated the
      inhibitory effects of rapamycin upon proliferation of IL-2 (CTLL-2) and IL-6
      (MH60.BSF-2) lymphokine-dependent cell lines. Lineweaver-Burk plots of the
      Michaelis-Menton equation suggested rapamycin inhibits IL-2 signal transduction
      in competitive, and IL-6 signal transduction in noncompetitive fashion,
      suggesting distinctive components of the various cytokine-receptor mechanisms. In
      vivo the cyclosporine/rapamycin combination exerted synergistic immunosuppression
      of rejection reactions in rats toward heterotopic cardiac allografts, using
      concentrations at which drugs were individually ineffective. These observations
      suggest that cyclosporine and rapamycin may be combined at significantly reduced
      doses to achieve unprecedented levels of immunosuppressive efficacy.

PMID- 1987693
TI  - The viability of microorganisms in preservation solutions.
AB  - In 1988 the University of Wisconsin solution was introduced into clinical
      transplantation. This solution is unique in that it contains no glucose but
      rather raffinose, lactobionate, and hydroxyethyl starch. In addition, it contains
      two antibiotics, penicillin and bactrim. Prior studies have shown that other
      preservation solutions allow the transmission of bacterial contamination from
      organ donor to recipient. However, there are no data on whether UW solution, with
      its unique composition and extended preservation times, allows bacterial
      transmission. We undertook the present study to establish if bacteria remain
      viable in UW solution at extended preservation times. Cultures of both aerobic
      (Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas
      aeruginosa) and anaerobic (Bacteroides fragilis) bacteria were suspended at
      10(5), 10(4), 10(2), and 10(1) org./ml (calibrated from a .5 Macfarland turbidity
      standard) in both Eurocollins and UW preservation solutions. Samples were then
      stored in an ice bath to stimulate organ preservation. The organisms were removed
      and plated on blood and chocolate agar at 0, 6, 12, 18, 24, and 36 hr
      postsuspension. The samples were then incubated at 37 degrees C and read for
      growth at 24-48 hr after plating. Our results showed growth of all organisms
      except S epi in both preservation solutions, at all dilutions and preservation
      times. S epi grew in the Eurocollins solution at all dilutions and preservation
      times but did not grow in the UW solution. When the experiment was repeated
      omitting penicillin from the UW solution, S epi grew at all dilutions and
      preservation times. These results demonstrate that in spite of the inclusion of
      two different antibiotics, the majority of the common bacterial contaminants of
      the organ donor remain viable in UW solution with extended preservation times. It
      may be possible therefore to omit these antibiotics from the UW solution and
      obtain similar results. It is also important to note that routine culturing
      remains an expensive but necessary part of organ procurement and preservation.

PMID- 1987694
TI  - Intragraft delivery of 16, 16-dimethyl PGE2 induces donor-specific tolerance in
      rat cardiac allograft recipients.
AB  - The stable prostaglandin E2 analogue, 16,16-dimethyl PGE2 (di-M-PGE2) was
      continuously infused by osmotic pump directly into rat heterotopic cardiac
      allografts. Intragraft delivery of 20 micrograms/kg/day di-M-PGE2 for 2 weeks
      completely prevented graft rejection for more than 150 days (n = 10), while
      untreated Buffalo recipients rejected Lewis cardiac allografts within 8 days
      after transplantation (mean survival time = 7.4 +/- 0.5 days, n = 5). When given
      for only 1 week, 20 micrograms/kg/day had a partial effect, since 60% of
      recipients accepted grafts long-term and 40% experienced rejection by day 14 (n =
      5). In contrast, systemic intravenous administration of 20 micrograms/kg/day di-M
      PGE2 for 2 weeks could not prolong graft survival (MST = 7.0 +/- 0.0 days, n =
      3), and the higher dose of 200 micrograms/kg/day resulted in death by day 2 (n =
      5). Long-term BUF recipients of LEW cardiac allografts accepted LEW donor strain
      skin grafts for more than 35 days while rejecting third-party Wistar Furth skin
      grafts in a normal fashion (MST = 7.3 +/- 0.5 days, n = 3), indicating the
      induction of donor-specific tolerance. Long-surviving LEW cardiac allografts
      retransplanted into naive BUF recipients were rejected within 7 days (MST = 6.7
      +/- 0.5 days, n = 3), indicating no change in graft immunogenicity. Therefore, a
      14-day infusion of di-M-PGE2 directly into a strongly MHC-mismatched cardiac
      allograft uniformly has resulted in long-term engraftment and the development of
      recipient donor-specific tolerance.

PMID- 1987695
TI  - Major histocompatibility complex antigens and murine islet allograft survival.
AB  - Immunomodulation of rodent islets can significantly prolong allograft survival.
      We utilized a murine model of primary islet transplantation to study the
      relationship between allograft survival and the quantitative pretransplant
      expression of class I and II MHC antigens in freshly isolated CBA/J islets, and
      islets subjected to 37 degrees C tissue culture, brief culture at 7 degrees C, or
      exposure of the donor to lipopolysaccharide. Seven-day culture resulted in
      decreased class II expression, a tendency to decreased class I expression, and a
      significant prolongation of allograft survival. Brief culture at 7 degrees C
      resulted in increased class I expression, a trend to decreased class II
      expression, and no significant change in allograft survival. Donor pretreatment
      with LPS resulted in increased class I expression without significant change in
      class II expression and was correlated with prolongation of allograft survival.
      These studies demonstrate that an upregulation of MHC class I by in vitro or in
      vivo islet pretreatment is not associated with an acceleration of islet
      rejection. Reduction of class II was associated with delayed rejection. These
      results do not support a major role of the indirect pathway of antigen
      presentation in islet rejection in vivo. Certain protocols that alter the usual
      expression of class I and II on pancreatic islets are associated with alteration
      in the initiation and/or propagation of the normal cell-mediated rejection
      process, suggesting that the concept of pretransplant treatment should continue
      to be pursued.

PMID- 1987696
TI  - Major histocompatibility complex restriction and cross-priming of H-Y antigen in
      rats.
AB  - Although female rats can be sensitized to H-Y-incompatible male skin isografts
      following exposure to MHC-incompatible male lymphoid cells, these cells are not
      as effective as MHC-compatible male cells. Evidence is presented that the
      effectiveness of the MHC-incompatible cells is a consequence of crosspriming and
      that such crosspriming only occurs if these cells are rejected.

PMID- 1987697
TI  - T cell subsets in the thymus of graft-versus-host immunosuppressed mice.
      Sensitivity of the L3T4+Lyt-2- subset to cortisone.
AB  - We have investigated the effects of graft-versus-host disease on T cell
      differentiation in the murine thymus. We previously reported that GVH-induced
      thymic dysplasia results in a T cell immunodeficiency associated with a lack of
      IL-2 production. This deficiency in IL-2 production may be the result of a
      reduction in the number of L3T4+Lyt-2- IL-2-producing cells or of a functional
      defect in this population. To test these two alternatives, flow cytometry
      analysis of L3T4 and Lyt-2 antigen expression on thymocytes along with
      immunofluorescence microscopy were employed to assess T cell phenotypes in
      thymuses of GVH mice. GVH reactions were induced by injecting 40 x 10(6) C57BL/6
      (B6) or A strain lymphoid cells into C57BL/6xAF1 (B6AF1) mice. Thymocyte
      populations were quantitated on different days after GVH induction. In the normal
      thymus, the ratio of L3T4/Lyt-2 single positive cells was greater than 2:1. In
      contrast, such a ratio was less than 1:1 in the atrophic GVH thymus, owing to a
      selective reduction in the number of L3T4+Lyt-2- cells. Following cortisone
      treatment the ratio of L3T4/Lyt-2 single positive thymocytes in normal F1 mice
      was approximately 3:1, whereas in GVH animals this ratio was reversed (1:2). This
      reversal was due to a selective reduction in the absolute numbers of L3T4+Lyt-2-
      cells. In adrenalectomized GVH animals, thymic cortical atrophy was prevented and
      normal ratios of L3T4/Lyt-2 single positive cells were observed. However, when
      these animals were treated with cortisone, the L3+T4/Lyt-2- population was more
      sensitive than was the L3T4- Lyt2+ population, thereby resulting in a 1:2
      L3T4/Lyt-2 ratio. These results demonstrate that single positive L3T4 cells are
      present in the murine GVH thymus, yet they have not acquired cortisone
      resistance, a trait normally attributed to this mature thymic subset. It appears
      that the GVH dysplastic thymus can support the differentiation of L3T4+Lyt-2-
      cells--however, such a thymus is unable to confer cortisone resistance upon this
      population. Consequently, these cells appear to be eliminated when exposed to
      corticosteroids in peripheral lymphoid tissue.

PMID- 1987698
TI  - RS-61443--a new, potent immunosuppressive agent.
AB  - The immunosuppressive activity of RS-61443, a semisynthetic derivative of
      mycophenolic acid, was examined in 33 canine renal allografts. Initial studies
      established that triple therapy consisting of 20 mg/kg RS-61443 in combination
      with 5 mg/kg cyclosporine and 0.1 mg/kg methylprednisolone was the optimal
      combination to prevent graft rejection. The median survival time was 8.1 +/- 1.2
      days in dogs without treatment (n = 5), 8.5 +/- 1.7 days in the treatment control
      group (CsA 5 mg/kg, MP 0.1 mg/kg; n = 6), 36.0 +/- 9.6 days with RS-61443
      monotherapy (40 mg/kg; n = 6); and 122.4 +/- 38.75 days with triple therapy (n =
      16). Graft prolongation was statistically significant when compared with controls
      (P less than 0.05 and 0.002, respectively). Six recipients in the triple therapy
      group survived over 150 days without major adverse effects. Long-term
      administration of RS-61443 (20 mg/kg/day) did not cause nephrotoxicity,
      hematotoxicity, or hepatotoxicity, with the exception of a slight elevation of
      the alkaline phosphatase levels. Gastrointestinal symptoms including gastritis,
      diarrhea, and anorexia were common, especially under 40 mg/kg RS-61443
      monotherapy, and appeared to be dose-related. Despite its immunosuppressive
      activity, an increased susceptibility to bacterial or viral infections was not
      observed. Histological studies of the kidney grafts revealed slight interstitial
      cell infiltration without vascular or glomerular damage.

PMID- 1987699
TI  - Liver transplantation in patients over sixty years of age.

PMID- 1987700
TI  - Successful transplantation of cadaveric en-bloc paired pediatric kidneys into
      adult recipients.

PMID- 1987701
TI  - Successful orthotopic liver transplantation in a child with Langerhans cell
      histiocytosis.

PMID- 1987702
TI  - Choice of cation in solutions for hypothermic storage of liver and heart. High
      sodium versus high-potassium.

PMID- 1987703
TI  - Beneficial and detrimental effects of RBC-adsorbed antilymphocyte globulin and
      prednisone on purified canine islet autograft and allograft function.
AB  - We have examined the effects of prednisone, cyclosporine, azathioprine, and RBC
      adsorbed goat antidog antilymphocyte globulin on islet graft function in totally
      pancreatectomized canines with purified, quantitatively defined, autologous, or
      allogeneic islets transplanted to the liver. The objectives were twofold: (1) to
      determine the potential detrimental effects to islet autograft function of the
      aforementioned agents, and (2) to determine the relative efficacy of the
      "nontoxic" agents in prolonging purified islet allograft function administered in
      doses that would be considered tolerable in human. The islet autograft studies
      demonstrated that prednisone given in doses of 1-2 mg/kg/day had a detrimental
      effect on islet autograft function, and that the combinations of
      immunosuppression involving CsA, azathioprine, and ALG were not detrimental to
      islet autograft function to the extent that hyperglycemia would ensue. In the
      subsequent allograft studies, three groups of canines received islet transplants:
      (1) controls (n = 5; 7860 +/- 750 islets/kg/weight), (2) canines given CsA and
      azathioprine (n = 6; 6810 +/- 890 islets/kg/body weight), and (3) canines given
      CsA, azathioprine, and RBC-adsorbed goat antidog ALG (n = 8; 6540 +/- 710
      islets/kg/body weight). The mean (+/- SE) day of rejection (serum glucose greater
      than or equal to 200 mg/dl) in the group of canine islet allograft recipients
      receiving CsA, azathioprine, and ALG was 11.8 +/- 1.4 days--significantly
      prolonged versus islet allograft recipients receiving no immunosuppression (mean
      survival 4.8 +/- 1.1 days, P less than 0.03), and versus allograft recipients
      receiving CsA/azathioprine without ALG (mean survival 4.4 +/- 1.4 days, P less
      than 0.05). Prednisone appears to be detrimental to islet graft function, even at
      low doses. ALG was not toxic, and significantly extended the survival of canine
      islet allografts. The inclusion of steroids as part of maintenance
      immunosuppression, or as treatment for acute rejection of islets, in human islet
      transplants should be reconsidered, whereas ALG or other antilymphocyte agents
      should continue to be used.

PMID- 1987704
TI  - Successful treatment of diabetes with the biohybrid artificial pancreas in dogs.
AB  - We have investigated a new hybrid artificial pancreas device to transplant islet
      allografts without immunosuppression. The device consists of a chamber through
      which passes a copolymer membrane connected to standard vascular grafts. Islets
      are placed inside the chamber but are outside of the blood stream. Nominal
      molecular porosity of 80,000 daltons permits free diffusion of nutrients and
      insulin across the membrane but inhibits the entry of immunoglobulins and
      immunocytes from the blood stream into the chamber. Initial studies focused on
      the technical feasibility of implanting the unseeded (no islets) devices. In 12
      normal mongrel dogs, the arterial limb of the device was anastomosed end-to-end
      to the common iliac artery and the venous limb end-to-side to the common iliac
      vein. Vascular patency was monitored by an audible bruit over the device. Two
      devices currently remain patent at 388 and 421 days. The remaining experiments
      failed due to thrombosis and membrane rupture, with 2 failing as late as 170 and
      279 days. In a second series, both arterial and venous anastomoses were done end
      to-side and dogs were placed on low-dose aspirin therapy. All 8 dogs are
      currently maintaining patent unseeded devices (96-226 days postimplantation).
      Subsequent studies determined the function of devices seeded with isolated canine
      pancreatic islet allografts in totally pancreatectomized, severely diabetic dogs.
      Diabetes was controlled by once-a-day insulin injection. After 2-3 weeks of
      diabetic control, a seeded device was implanted. Diabetic control was monitored
      by fasting blood levels and postprandial and intravenous glucose tolerance tests,
      and vascular patency by the loudness of the bruit. In the first series of 6 dogs
      given seeded devices without aspirin, no significant function was discernible,
      with failure attributable to thrombosis, poor islet viability, and surgical
      complications. In the second series of 13 dogs given aspirin, 8 dogs have
      required an appreciably lower dose of injected insulin to maintain fasting blood
      glucose at acceptable levels. Of note are 4 dogs that required virtually no
      exogenous insulin for at least 3 weeks. One dog lost function on day 74 and
      another still requires no insulin at 267 days postimplantation. However, despite
      normal fasting glucose levels, the glucose tolerance tests showed delayed return
      to normal levels. Weight lost following pancreatectomy was rapidly regained in
      the presence of a functioning seeded device. Histologic examination of the
      removed devices revealed no signs of rejection.

PMID- 1987705
TI  - Resistance to graft-versus-host disease following small bowel transplantation.
AB  - Transplantation of a Lewis rat small bowel allograft (SBTx) into Lewis x Brown
      Norway F1 (LBNF1) hybrid recipients provokes lethal graft-versus-host disease.
      GVHD in F1 hybrid rats inoculated with large number of parental lymphocytes may
      be abrogated by prior treatment of F1 hybrids with a sublethal dose (SLD) of the
      same parental lymphocytes. Therefore, we sought to determine whether this type of
      immunomodulation would prevent GVHD after SBTx. We examined whether pretreatment
      of LBNF1 recipients with a SLD of parental lymphocytes, or with a revascularized
      segment of parental small bowel, might ameliorate GVHD following transplantation
      of the entire parental small bowel. Nonpretreated LBNF1 recipients died of GVHD
      after entire Lew SBTx; 95% of LBNF1 recipients pretreated with SLD of Lew
      lymphocytes and 84% of LBNF1 recipients first transplanted with a segment of Lew
      small bowel survived GVHD induced by entire Lew SBTx 10 days later. Of LBNF1
      recipients pretreated with SLD of Brown Norway lymphocytes or first transplanted
      with a segment of BN small bowel, none were protected from GVHD induced by entire
      Lew SBTx 10 days later. We concluded that pretreatment of LBNF1 recipients either
      with an SLD of parental lymphocytes or with a segment of parental small bowel
      provides profound protection from the effects of GVHD following transplantation
      of an entire small bowel of the same parental strain specificity.

PMID- 1987706
TI  - The role of tumor necrosis factor in allograft rejection. III. Evidence that anti
      TNF antibody therapy prolongs allograft survival in rats with acute rejection.
AB  - We have previously demonstrated that TNF-alpha levels are elevated in liver
      transplant patients experiencing acute rejection. In addition, prophylactic
      administration of anti-TNF-alpha or anti-TNF-beta antibodies prolonged graft
      survival in a rat heterotopic cardiac transplant model. This experiment was
      designed to evaluate anti-TNF therapy in the treatment of acute allograft
      rejection. Heterotopic cardiac transplants were performed using Buffalo donors
      and Lewis recipients. Histologic sections of transplanted grafts from untreated
      animals revealed significant rejection at day 4 with terminal rejection occurring
      on day 10.8 +/- 0.4. Animals in the experimental groups received antirejection
      therapy from postoperative days 4-13. Treatment with cyclosporine at 2 mg/kg/day
      prolonged graft survival to 16.5 +/- 2.0 days (P = 0.01 versus controls).
      Administration of polyclonal anti-TNF-alpha in combination with polyclonal anti
      TNF-beta increased graft survival to 14.6 +/- 0.4 days (P less than 0.001 versus
      controls). Use of a monoclonal anti-TNF-alpha antibody was even more effective,
      with graft survival of 17.4 +/- 0.7 days (P less than 0.001 versus controls).
      Combination immunotherapy with monoclonal anti-TNF-alpha in conjunction with CsA
      extended survival to greater than 30 days. In contrast, recombinant TNF-alpha (5
      micrograms/day, i.p.) markedly accelerated the time to graft failure (7.4 +/- 0.2
      days, P less than 0.001 versus controls). Examination of explanted graft tissue
      on postoperative day 9 from animals treated with anti-TNF showed decreased
      mononuclear cell infiltrate when compared to untreated animals. Treatment with
      TNF-alpha markedly increased the inflammatory process. These results suggest that
      TNF may play a role in the pathogenesis of acute rejection.

PMID- 1987707
TI  - Prolonged pancreas preservation using a simplified UW solution containing
      polyethylene glycol.
AB  - The University of Wisconsin solution is considered the most effective universal
      flush and cold storage solution to date, and is now being widely applied
      clinically in organ transplantation. The results of this study show that
      Cardiosol, a modified cardioplegic solution containing 5% polyethylene glycol
      (PEG20M, MW 17,000 daltons), is significantly superior to UW (P less than 0.001)
      in the flush perfusion and hypothermic storage of pancreases for more than 36 hr
      prior to transplantation into streptozotocin-induced diabetic rats. When the
      pancreases were stored in Cardiosol, the 1-week survival rate was 7 of 10 (70%)
      after 24 hr of preservation; 7 of 12 (58%) after 36 hr; and 3 of 10 (30%) after
      48 hr. In contrast, when the pancreases were stored in UW solution, the 1-week
      survival rate was 8 of 12 (67%) after 24 hr of preservation; after 36 hr, no
      animal survived (0 of 14). Intravenous glucose tolerance test K-values (decline
      in glucose concentration, percentage per minute) were normal in both groups
      receiving 24-hr-preserved pancreases, ranging from 2.60 to 4.16. Of interest, the
      peak insulin response 1 min following intravenous glucose was significantly
      higher (P less than 0.01) in the Cardiosol-preserved organs (303 +/- 29.8
      microU/ml) (+/- SEM) than in the glands preserved in UW solution (112 +/- 47.9
      microU/ml). We conclude that Cardiosol allows prolonged whole organ pancreas
      preservation in the rat transplant model.

PMID- 1987708
TI  - Long-term results of a controlled prospective study with transfusion of donor
      specific bone marrow in 57 cadaveric renal allograft recipients.
AB  - Experimental studies have shown that antilymphocyte globulin combined with
      transfusion of donor-specific bone marrow cells can induce partial tolerance to
      allograft tissue. We have adapted these protocols to clinical use and present the
      results of 57 cadaveric renal allograft recipients who received Minnesota ALG
      followed by the transfusion of cryopreserved donor-specific bone marrow. A group
      of 54 patients received the contralateral kidney and similar immunosuppression
      without the marrow transfusion and serve as controls. Both groups received
      quadruple immunosuppression with MALG, cyclosporin, azathioprine, and prednisone.
      In the bone marrow group, after a 10-14 day induction course of ALG,
      cryopreserved marrow was transfused on the seventh day after the last dose of
      ALG. The median follow-up in both groups is 16 months, (range 2.5-33 months). Six
      grafts have been lost in the bone marrow group, (three rejections, 2 deaths [Cr
      2.0, 2.3], 1 recurrent disease). In the control group 16 grafts have been lost
      (13 rejections, 3 deaths [Cr 1.7, 2.5, 3.0]). Five patients in the control group
      have biopsy-proved chronic rejection compared to one in the bone marrow group. 17
      patients in the bone marrow group have been tapered off the prednisone, and three
      of these patients have had mild late rejection episodes without graft loss. The
      two groups were compared for differences in the number of rejection episodes,
      estimated renal plasma flow, glomerular filtration rate, and urine protein. No
      differences were found. The allograft survival of the bone marrow group was
      significantly greater (P less than .01) than the control group. The graft
      survival rates for the bone marrow group at 12 and 18 months were 90% (confidence
      limits [CL] 85-94) and 85% (CL 78-90), respectively. In the the control group the
      12 and 18 month allograft survival rates were 71% (CL 63-78) and 67% (CL 58-74),
      respectively. The survival in the control group was similar to our overall
      transplant experience with quadruple therapy. Mixed lymphocyte culture analysis
      shows a trend to diminished donor-specific responsiveness in the bone marrow
      group. The use of cryopreserved donor-specific bone marrow is associated with
      improved allograft survival in cadaveric kidney allograft recipients. However, a
      more effective induction protocol is needed to reduce the overall number of
      rejection episodes.

PMID- 1987710
TI  - Hepatic allograft rescue following arterial thrombosis. Role of urgent
      revascularization.
AB  - Hepatic artery thrombosis is a continuing source of morbidity and mortality
      following orthotopic liver transplantation. The cornerstone of therapy has been
      urgent retransplantation that is limited by organ availability. For this reason
      we developed a policy of urgent revascularization for allograft rescue. Hepatic
      artery thrombosis developed following 15 transplants of which 11 underwent urgent
      rearterialization. The diagnosis was made a mean of 4.8 days (range 1-10)
      following transplantation. Duplex ultrasonography was diagnostic in all patients
      and confirmed by angiography in 4 (36%). Three patients with hepatic artery
      thrombosis were identified following screening ultrasonography and were
      clinically unsuspected. Upon reexploration, a specific technical reason for
      hepatic artery was found in 4 patients (36%). Twelve arterial revascularization
      procedures were performed in 11 patients including: thrombectomy alone (n = 4);
      revision of anastomosis with thrombectomy (n = 5); and thrombectomy with
      placement of vascular conduit (n = 3). Following revascularization, 8 patients
      maintained hepatic artery patency. Three patients eventually required
      retransplantation secondary to biliary sepsis. Biliary tract complications
      developed in 6 patients, at a mean of 23 days following revascularization and
      included: breakdown of the biliary anastomosis (n = 4); stricture (n = 1); and
      sludge formation (n = 1). The overall graft and patient survival are 74% and 82%
      respectively, with a mean follow-up of 6.8 months. Hepatic allograft rescue with
      the use of urgent revascularization following hepatic artery thrombosis appears
      to be an effective means of either avoiding retransplantation or providing a
      bridge until a suitable donor becomes available.

PMID- 1987709
TI  - Results of our first nine intraportal islet allografts in type 1, insulin
      dependent diabetic patients.
AB  - With the first demonstration of insulin independence following intraportal islet
      transplantation into a patient with type 1 diabetes, a new era of clinical islet
      transplantation will begin. This report provides our initial experience of
      clinical islet transplantation with a total of nine consecutive portal vein islet
      transplants in seven diabetic recipients. The first three transplants were done
      in nonrenal failure diabetics (NRFI) using 6319 +/- 2173 islets/kg body weight
      with islets processed from single pancreas and cultured for 7 days at 24 degrees
      C. Prednisone, azathioprine, and cyclosporine were initiated prior to transplant.
      While all three recipients demonstrated C-peptide function posttransplant, all
      three rejected their grafts at 2 weeks. Five days of OKT3 treatment failed to
      recover more than 10% of their rejecting islet grafts. The studies were then
      shifted to established kidney transplant recipients (EKI) maintaining their basal
      immunosuppression while adding 7 days of Minnesota antilymphoblast globulin
      (MALG) to the recipient using islets from single donor pancreas that had been
      cultured for 7 days at 24 degrees C. There were an average of 6161 +/- 911 islets
      transplanted intraportally into three EKI recipients. All three had C-peptide
      response from the transplant, but none achieved insulin independence. While the
      first patient rejected his graft at 2 weeks, two recipients demonstrated long
      term islet function up to 10 months posttransplant. Sustacal challenge testing
      demonstrated C-peptide responsiveness, but in a delayed pattern suggesting
      insufficient islet mass had been transplanted. The next three kidney transplant
      recipients received islets from more than one donor pancreas averaging 13,916 +/-
      556 islets/kg body weight. The first of these was the first to achieve insulin
      independence from 10 to day 25 posttransplant when she appeared to have a
      rejection episode. The second and third recipients were retransplanted with
      islets from multiple donors having achieved partial islet function from single
      pancreas donor. The first patient on triple immunosuppression is demonstrating
      long-term partial function at 184 days but is not insulin independent. The third
      patient on prednisone and azathioprine received one half his islets after 7-day
      culture and the other half after 7-day culture combined with cryopreservation. He
      is continuing to demonstrate insulin independence for 154 days post-transplant
      with a glycated hemoglobin value of 5.6%. Sustacal challenge data demonstrate a
      total stimulated C-peptide response of 155 rhomol/ml at 4 months post-transplant
      compared with 148 +/- 12 rhomol/ml for normal controls (NC) and 425 rhomol/ml for
      nondiabetic, established kidney transplant recipients on triple
      immunosuppression.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1987711
TI  - Interpreting results of exercise studies after acute myocardial infarction
      altered by thrombolytic therapy, coronary angioplasty or bypass.
AB  - Numerous studies have assessed the ability of exercise modalities to predict
      patient outcome after acute myocardial infarction (AMI). Implicit in the use of
      these prior data to assess the prognosis of patients currently undergoing
      exercise studies is the assumption that patients selected for exercise assessment
      are similar over time and that the data generated in the past are therefore
      applicable to the current patient populations. This study retrospectively
      assessed the clinical, exercise, and rest and exercise radionuclide angiographic
      data in 791 consecutive patients referred for exercise radionuclide angiography
      within 1 month after AMI during a 5-year period to determine if the clinical and
      exercise characteristics of patients referred for exercise evaluation after
      infarction have changed significantly over time. Most parameters examined
      demonstrated significant increasing trends, including thrombolytic therapy at the
      time of AMI, revascularization procedure between AMI and exercise assessment,
      age, beta-blocker usage, Q-wave AMI, inferior infarction, exercise double
      product, exercise capacity, significant ST-segment depression with exercise, peak
      ejection fraction, and change in ejection fraction with exercise. These data
      indicate that the characteristics of patients selected to undergo exercise after
      AMI in a large referral center have changed significantly over time. If these
      data are applicable to other referral centers and to other exercise testing
      modalities, previously published results regarding exercise assessment after AMI
      will need to be reconfirmed in patients currently selected for testing, since
      these results may no longer be applicable in this current era of aggressive
      medical and interventional management.

PMID- 1987712
TI  - In-hospital symptoms of psychological stress as predictors of long-term outcome
      after acute myocardial infarction in men.
AB  - The impact of high levels of psychological stress symptoms in the hospital after
      an acute myocardial infarction (AMI) was examined over 5 years among 461 men who
      took part in a trial of psychological stress monitoring and intervention.
      Psychological stress was assessed using the 20-item General Health Questionnaire
      (GHQ) 1 to 2 days before hospital discharge. Once discharged, patients in the
      treatment group responded to the GHQ by telephone on a monthly basis and, when
      they reported high levels of stress symptoms (GHQ greater than or equal to 5),
      received visits from nurses to help them deal with their life problems. Control
      patients received routine medical care after discharge. Post-hoc subgroup
      analyses based on life-table methods showed that, for patients receiving routine
      care after discharge, high stress (GHQ greater than or equal to 5) was associated
      with a close to threefold increase in risk of cardiac mortality over 5 years (p =
      0.0003) and an approximately 1.5-fold increase in risk of reinfarction over the
      same period (p = 0.09). In contrast, highly stressed patients who took part in
      the 1-year program of stress monitoring and intervention did not experience any
      significant long-term increase in risk. Although program impact was significant
      in terms of reduction of both cardiac mortality (p = 0.006) and AMI recurrences
      (p = 0.004) among highly stressed patients, there was little evidence of impact
      among patients with low levels of stress in the hospital.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1987713
TI  - Effect of nifedipine on total ischemic activity and circadian distribution of
      myocardial ischemic episodes in angina pectoris.
AB  - A randomized, double-blind, crossover study was conducted in 10 patients to
      assess the effect of nifedipine versus placebo on total ischemic activity and
      circadian distribution of ischemic episodes. After baseline exercise treadmill
      testing and 48-hour ambulatory electrocardiographic ST-segment monitoring,
      patients received either nifedipine (mean dose, 80 mg/day) or placebo
      administered 4 times per day, with the initial dose taken immediately upon
      arising in the morning. Patients were maintained on a stable dose of each study
      drug for 7 days, after which they underwent repeat exercise treadmill testing and
      48-hour ambulatory electrocardiography. During exercise treadmill testing,
      greater exercise duration was achieved by patients receiving nifedipine than by
      those receiving placebo (421 +/- 121 vs 353 +/- 155 seconds, respectively; p less
      than 0.05). Time to greater than or equal to 1 mm ST depression was significantly
      greater with nifedipine (282 +/- 146 seconds) than at baseline (130 +/- 72
      seconds, p less than 0.003) and with placebo (150 +/- 98 seconds, p less than
      0.0005). During ambulatory electrocardiographic monitoring, nifedipine reduced
      both the total number of ischemic episodes (18 vs 54 at baseline and 63 with
      placebo; p less than 0.02 for both) and the total duration of ischemia (260 vs
      874 at baseline and 927 minutes with placebo; p less than 0.02 for both). The
      surge of ischemia between 06:00 and 12:00 noted at baseline and during placebo
      therapy was nearly abolished during nifedipine treatment. Nifedipine at this
      dosage, administered in this manner, is effective in reducing total ischemic
      activity and may prevent morning surges of ischemic episodes.

PMID- 1987714
TI  - Early assessment of coronary artery bypass graft patency by high-dose
      dipyridamole echocardiography.
AB  - To assess the role of high-dose (up to 0.84 mg/kg during 10 minutes) dipyridamole
      echocardiographic testing in the evaluation of coronary artery bypass graft
      patency early after surgery, 18 consecutive patients with angina underwent
      dipyridamole echocardiography and coronary angiography before and 7 to 10 days
      after bypass surgery. Coronary angiography showed 2- or 3-vessel disease in 7 and
      11 patients, respectively. A total of 53 bypass grafts were performed. Before
      bypass surgery 14 patients had a positive and 4 a negative test result. No
      complication occurred during the test performed early after surgery. Of the 14
      patients with positive dipyridamole echocardiographic results before surgery, 10
      had negative and 4 had positive results after surgery. All 4 patients had
      negative results before and after surgery. In the 4 patients with positive
      results after dipyridamole echocardiographic testing before and after bypass
      surgery, dipyridamole time increased from 5.8 +/- 5 to 9.3 +/- 0.9 minutes (p =
      0.3) after the procedure and wall motion score index at peak dipyridamole changed
      from 1.55 +/- 0.2 to 1.28 +/- 0.3 (p = 0.05). Forty-nine of 53 grafts were patent
      as seen on angiography. Dipyridamole echocardiographic results were positive in 4
      of 5 patients who had at least 1 obstructed graft or native vessel obstructed
      distal to bypass graft insertion. The remaining patient had diagnostic
      electrocardiographic changes during dipyridamole infusion without wall motion
      abnormalities. Dipyridamole echocardiographic results were negative in all 13
      patients who had complete revascularization. In the 4 patients with positive test
      results, the procedure correctly identified the localization of the diseased
      bypass graft.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1987715
TI  - Ablation of the atrioventricular junction with radiofrequency energy using a new
      electrode catheter.
AB  - Percutaneous catheter ablation using radiofrequency energy can be used to
      interrupt atrioventricular (AV) conduction in patients with supraventricular
      tachycardia refractory to drugs. Results of radiofrequency ablation of the AV
      junction using a custom-designed catheter with a large, 3-mm-long distal
      electrode, 2-mm interelectrode spacing, and a shaft with increased torsional
      rigidity were compared with those using a standard quadripolar electrode catheter
      (Bard EP). An electrocoagulator (Microvasive Bicap 4005) supplied unmodulated
      radiofrequency current at 550 kHz, which was applied between the distal electrode
      of the ablation catheter and a large skin electrode. With use of the modified
      catheter, 12 of 13 patients (92%) had persistent complete AV block induced with 7
      +/- 5 applications of 18 +/- 6 W of radiofrequency power. In contrast, complete
      AV block was produced in only 9 of 18 (50%) historical control patients treated
      with the standard catheter, despite a similar number of applications (7 +/- 5)
      and power output (16 +/- 4 W). A rise in impedance, due to desiccation of tissue
      and coagulum formation, occurred earlier (28 +/- 18 vs 52 +/- 24 seconds, p less
      than 0.001) and more frequently (54 vs 40% of applications, p = 0.047) in
      patients treated with the standard catheter than in patients treated with the
      modified catheter. The use of a catheter designed to increase the surface area of
      electrode-tissue contact allows more radiofrequency energy to be delivered before
      a rise in impedance occurs and appears to increase the effectiveness of
      radiofrequency ablation of the AV junction.

PMID- 1987716
TI  - Relative importance of activation sequence compared to atrioventricular synchrony
      in left ventricular function.
AB  - This study evaluated the relative hemodynamic importance of a normal left
      ventricular (LV) activation sequence compared to atrioventricular (AV) synchrony
      with respect to systolic and diastolic function. Twelve patients with intact AV
      conduction and AV sequential pacemakers underwent radionuclide studies at rest
      and Doppler echocardiographic studies at rest and during submaximal exercise,
      comparing atrial demand pacing (AAI) to sequential AV sensing pacing (DDD) and
      ventricular demand pacing (VVI). Studies at rest were performed at a constant
      heart rate between pacing modes, and the exercise study was performed at a
      constant heart rate and work load. Cardiac output was higher during AAI than
      during both DDD and VVI (6.2 +/- 1 vs 5.6 +/- 1 and 5.3 +/- 1 liters/min, p less
      than 0.05). LV ejection fraction was likewise higher during AAI (55 +/- 12 vs 49
      +/- 11 vs 51 +/- 13, p less than 0.05). VVI with or without AV synchrony was
      associated with a paradoxical septal motion pattern, resulting in a 25%
      impairment of regional septal ejection fraction. In addition, LV contraction
      duration was more homogenous during AAI. Peak filling rate during AAI and VVI was
      higher than during DDD (2.86 +/- 1 and 2.95 +/- 1 vs 2.25 +/- 1 end-diastolic
      volume/s; p less than 0.05). During VVI, the time to peak filling was
      significantly shorter than during both AAI and DDD (165 +/- 34 vs 239 +/- 99 and
      224 +/- 99 ms; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1987717
TI  - Effect of mitral regurgitation and volume loading on pressure half-time before
      and after balloon valvotomy in mitral stenosis.
AB  - Doppler pressure half-time (PHT) is frequently used to assess mitral valve area
      (MVA), but the reliability of PHT has recently been challenged, specifically in
      the setting of balloon mitral valvotomy when hemodynamics have been abruptly
      altered. The effect of volume loading both before and after balloon mitral
      valvotomy on computation of MVA by Gorlin and by PHT in 18 patients with high
      fidelity micromanometer measurements of left atrial and left ventricular pressure
      was therefore examined. Echocardiographic MVA increased from 0.91 +/- 0.15 to
      1.97 +/- 0.42 cm2 after valvotomy. Volume loading produced significant increases
      in left atrial pressure (16 to 23 before and 12 to 20 mm Hg after valvotomy), in
      cardiac output (3.7 to 4.1 before and 3.9 to 4.6 liters/min after valvotomy), and
      in mitral valve gradient (11 to 14 before and 5 to 7 mm Hg after valvotomy).
      These hemodynamic changes were associated with modest but significant decreases
      in PHT and increases in MVA estimated by 220/PHT (0.66 to 0.81 before and 1.64 to
      1.96 cm2 after valvotomy), whereas the MVA by Gorlin was not affected in a
      consistent fashion by volume loading (0.85 to 0.89 before and 1.66 to 1.69 cm2
      after valvotomy). The correlation between Gorlin MVA and 220/PHT was only fair (r
      = 0.73, p less than 0.001) and was significantly poorer among patients with
      greater than 1+ mitral regurgitation (r = 0.72) than among those with less or no
      regurgitation (r = 0.79) (p = 0.001 by analysis of covariance for mitral
      regurgitation effect).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1987718
TI  - Sudden death during empiric amiodarone therapy in symptomatic hypertrophic
      cardiomyopathy.
AB  - Amiodarone is reported to improve symptoms and to prevent sudden death in
      patients with hypertrophic cardiomyopathy (HC). Amiodarone treatment (loading
      dose 30 g given over 6 weeks; maintenance dose 400 mg/day) was prospectively
      evaluated in 50 patients with HC in whom the drug was initiated because of
      symptoms refractory to conventional drug therapy (calcium antagonists and beta
      blockers). Twenty-one (42%) patients had ventricular tachycardia (VT) during
      Holter monitoring. Amiodarone significantly and often markedly improved the
      patients' New York Heart Association functional class status (from 3.3 to 2.7 at
      2 months, p less than 0.001) and treadmill exercise duration (p less than 0.001).
      Eight patients, however, died (7 suddenly) during a mean follow-up period of 2.2
      +/- 1.8 years. Of the 7 sudden deaths, 6 occurred within 5 months of initiation
      of treatment. The 6-month and 1- and 2-year survival rates were 87, 85 and 80%,
      respectively. The survival rate of patients with VT was significantly worse than
      that of patients without VT (61 vs 97% at 2 years; p less than 0.01). Sudden
      death occurred despite abolition of VT on Holter monitoring. Amiodarone increased
      left ventricular peak filling rate by radionuclide angiography in 20 of 33
      patients (61%) (p less than 0.01). Decrease in peak left ventricular filling rate
      within 10 days of amiodarone therapy (8 of 33 patients) was associated with
      subsequent sudden death (p less than 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1987719
TI  - Value of electrophysiologic studies in hypertrophic cardiomyopathy treated with
      amiodarone.
AB  - The relation of electrophysiologic effects of amiodarone to long-term outcome was
      studied in 35 patients with hypertrophic cardiomyopathy (HC). Indications for
      electrophysiologic studies were: cardiac arrest (n = 3), syncope/presyncope (n =
      27) and asymptomatic ventricular tachycardia (VT) (n = 5). Twenty-eight patients
      (80%) had VT, 3 (9%) atrial tachycardia and 3 (9%) paroxysmal atrial fibrillation
      during 24-hour Holter monitoring. The studies were repeated after a total
      amiodarone dose of 58 +/- 122 g and during a maintenance median daily dose of 400
      mg. Amiodarone abolished paroxysmal atrial arrhythmias in all 6 patients.
      However, it caused marked atrioventricular nodal conduction abnormality in 3
      patients and heart block or marked HV interval prolongation (to greater than or
      equal to 100 ms) in 4 patients. Sustained VT was induced in 26 patients (74%) at
      baseline study and in 23 patients (66%) taking amiodarone therapy. With
      amiodarone, VT was no longer inducible or was more difficult to induce in 11
      patients (31%), and the drug abolished VT during Holter monitoring in all
      patients. However, VT was easier to induce with amiodarone or was induced only
      with amiodarone in 18 (51%) patients. Amiodarone significantly slowed the rate of
      induced VT (from 248 +/- 29 to 214 +/- 37 beats/min, p less than 0.001). This was
      associated with a change in its morphology from polymorphic to monomorphic VT in
      7 patients. During a follow up of 18 +/- 14 months (range 2 to 56), amiodarone
      was discontinued because of adverse effects in 8 patients (23%).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1987720
TI  - Rarity of preclinical alcoholic cardiomyopathy in chronic alcoholics less than 40
      years of age.
AB  - Preclinical alcoholic cardiomyopathy, myocardial damage in the absence of overt
      congestive heart failure in chronic alcoholics, is well characterized at
      necropsy, but attempts to identify such a clinical entity before death have
      produced conflicting results. Studying subjects only at rest, the inclusion of
      older alcoholics and limitations of noninvasive techniques may explain some of
      the disagreement. To determine if preclinical alcoholic cardiomyopathy could be
      identified independent of the aforementioned limitations, 25 asymptomatic chronic
      alcoholics aged less than 40 years (mean 34), each of whom had consumed a minimum
      of 1 pint of whiskey or one 6-pack of beer greater than or equal to 5 days per
      week for greater than or equal to 5 years, underwent radionuclide
      ventriculography for measurements of systolic and diastolic function at rest,
      peak supine exercise and during recovery, and echocardiography for assessment of
      chamber size, wall thickness and left ventricular mass. Red blood cell levels of
      selenium and thiamine were measured to determine whether abnormalities were
      present in these 2 potential mediators of alcoholic cardiomyopathy. For
      comparison, an age-matched group of healthy control subjects was also studied.
      For alcoholics and control subjects at rest, mean ejection fraction (67 +/- 7% vs
      71 +/- 6%) and diastolic peak filling rate (3.4 +/- 0.6 vs 3.3 +/- 0.6 end
      diastolic volumes per second [EDV/s]) were similar.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1987721
TI  - Prognostic value of thallium-201 perfusion defects in idiopathic dilated
      cardiomyopathy.
AB  - To assess the prognostic significance of thallium-201 perfusion defects in
      patients with idiopathic dilated cardiomyopathy (IDC), 43 patients underwent
      thallium scintigraphy in addition to clinical, echocardiographic, angiographic
      and hemodynamic evaluation. Eleven patients had no significant thallium perfusion
      abnormality, 19 had multiple small defects and 13 had a large defect. During 3.2
      +/- 2.2 years, 14 patients had disease-related mortality. The patients who died
      had a higher incidence of ventricular tachycardia (71 vs 31%; p less than 0.02),
      increased cardiothoracic ratio (60 +/- 6 vs 54 +/- 6; p = 0.005), decreased
      fractional shortening (11 +/- 6 vs 15 +/- 5; p less than 0.05), increased
      pulmonary wedge pressure (15 +/- 7 vs 10 +/- 6 mm Hg; p = 0.05), increased left
      ventricular end-diastolic pressure (21 +/- 8 vs 14 +/- 6 mm Hg; p = 0.02) and
      abnormal thallium perfusion defects (13 of 14 vs 16 of 26; p less than 0.05)
      compared with survivors. Age, gender, left ventricular end-systolic and end
      diastolic dimensions, cardiac index and ejection fraction were not statistically
      different in the survivors versus the patients who died. Kaplan-Meier survival
      estimates at 1, 3 and 5 years were 100% in patients without significant perfusion
      abnormality; 89, 77 and 64%, respectively, in patients with multiple small
      defects; and 84, 76 and 30%, respectively, in patients with a large defect (p
      less than 0.025 by log rank test).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1987722
TI  - Usefulness of color-flow Doppler in diagnosing and in differentiating
      supracristal ventricular septal defect from right ventricular outflow tract
      obstruction.
AB  - Color-flow Doppler is used for special localization of cardiac flows. The
      transeptal jet in supracristal ventricular septal defect (VSD) is directed toward
      the pulmonary valve and is often difficult to distinguish from the right
      ventricular (RV) outflow tract flow. Pulsed- and continuous-wave Doppler can
      misread the VSD jet as a stenotic lesion in the RV outflow tract. This study
      describes the color-flow Doppler characteristics of supracristal VSD and
      determines if color-flow Doppler can differentiate supracristal VSD jets from RV
      outflow tract flow. The study group comprised 28 patients ranging in age from 3
      days to 23 years (mean 6.4), with catheter-diagnosed supracristal VSD in 14,
      isolated pulmonary valve stenosis in 10 and RV infundibular obstruction in 4. The
      echocardiographic Doppler and color-flow Doppler data of all patients were
      reviewed without knowledge of catheterization diagnosis. In all patients with
      supracristal VSD, color-flow Doppler revealed an abnormal transeptal jet directed
      toward the pulmonary valve that occurred 5 to 10 ms before RV outflow tract flow
      was identified. VSD and RV outflow tract jet could be differentiated by pulsed-
      and continuous-wave Doppler alone in 10 of 14 patients (71%). In 4 patients,
      differentiation was possible only with color-flow Doppler and
      electrocardiographic gating. Associated aortic regurgitation, or a fistula, or
      both, were detected in 6 patients. Pulsed- and continuous-wave Doppler with or
      without color-flow Doppler correctly identified the level of obstruction in all
      patients with RV outflow tract lesions (14 of 14). Supracristal VSD jet occurs in
      early systole and is directed toward the pulmonary valve.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1987723
TI  - Accuracy of assessment of cardiac vagal tone by heart rate variability in normal
      subjects.
AB  - The correlations of 11 indexes of heart rate variability were examined with
      pharmacologically determined cardiac vagal tone in 15 normal subjects at supine
      rest. After sympathetic influences by intravenous propranolol were eliminated, RR
      interval variability was measured for 10 minutes under controlled respiration
      (0.25 Hz), and cardiac vagal tone was determined as the decrease in mean RR
      interval following complete vagal blockade with atropine. Time domain indexes
      (standard deviation, coefficient of variance and mean successive difference)
      correlated strongly with vagal tone (r = 0.87, 0.81 and 0.92, respectively; p
      less than 0.001 for all). The same was true for frequency domain indexes for the
      high-frequency (0.25 Hz) component calculated both by autoregressive spectrum
      analysis (square root of power and coefficient of component variance) and by fast
      Fourier transform (mean amplitude) (r = 0.91, 0.85 and 0.86, respectively; p less
      than 0.0001 for all). However, frequency domain indexes for the low-frequency
      spectral component (0.03 to 0.15 Hz) correlated less strongly (r = 0.69, 0.55 and
      0.70, respectively), and the fraction of power [power/(total power greater than
      0.03 Hz)] of both components showed no correlation. Principal component analysis
      showed that the first 6 indexes with strong correlations contained solely the
      first principal component closely related to vagal tone, whereas the remaining 5
      indexes also contained the second component unrelated to vagal tone. These
      results indicate that most of the time and frequency domain analyses in use
      provides an accurate and common measure of cardiac vagal tone at rest.

PMID- 1987724
TI  - Significance of minimal preexcitation in Wolff-Parkinson-White syndrome.

PMID- 1987725
TI  - Comparison of responses to isoproterenol and epinephrine during head-up tilt in
      suspected vasodepressor syncope.

PMID- 1987726
TI  - Frequency of valvular regurgitation by color Doppler echocardiography in systemic
      lupus erythematosus.

PMID- 1987727
TI  - Hemodynamic study during upright isotonic exercise before and six months after
      dynamic cardiomyoplasty for idiopathic dilated cardiomyopathy or Chagas' disease.

PMID- 1987728
TI  - Prognosis of nonobstructive hypertrophic cardiomyopathy.

PMID- 1987729
TI  - Left ventricular function in patients greater than 20 years of age with Ebstein's
      anomaly of the tricuspid valve.

PMID- 1987730
TI  - ST-segment depression after cardiac transplantation and its usefulness as an
      indicator of acute rejection.

PMID- 1987731
TI  - Usefulness of systolic excursion of the mitral anulus as an index of left
      ventricular systolic function.

PMID- 1987732
TI  - The residual mediastinal mass following radiation therapy for Hodgkin's disease.
AB  - Thirty-two patients with mediastinal involvement by Hodgkin's disease (HD),
      treated with an isocentric technique of extended-field radiation therapy (RT)
      with or without chemotherapy, are described. Twenty-nine patients (91%) had a
      complete response to therapy and four patients subsequently relapsed, with a
      median follow-up of 54 months. Five of seven patients not in continuous complete
      remission were salvaged, with one additional salvage therapy. Ten patients had
      persistent mediastinal masses at 1 year, following completion of planned therapy;
      only one of these has had recurrent disease. Of those who achieved complete
      response, only one patient has had disease recurrence in the mediastinum. We
      conclude that extended-field RT, using an isocentric technique, provides
      excellent local disease control in HD; however, persistent mediastinal widening
      after therapy is frequent, and additional therapy should not be given in the
      absence of conclusive evidence of disease progression.

PMID- 1987733
TI  - Radiation therapy of pituitary tumors: results in 95 cases.
AB  - Between 1967 and 1985 95 patients with pituitary adenoma received radiation
      therapy at the University of California, Los Angeles (UCLA), and the West Los
      Angeles Veterans' Administration (VA) Medical Center. Seventy of these patients
      received radiation therapy immediately as adjuvant therapy following incomplete
      resection, and 25 were irradiated as primary treatment or after surgical failure.
      The majority of cases (87%) presented clinically with macroadenomas. Two-thirds
      of the patients were treated with parallel opposed lateral portals to a midline
      total dose of 50 Gy. The mean follow-up was 7 years (range: 30-250 months). In
      our series, there is a difference in response by disease subtype. The control
      rates were 83% (30 of 36) for nonfunctioning adenoma, 60% (nine of 15) for growth
      hormone secreting adenoma, 44% (16 of 36) for prolactin secreting adenoma, three
      of five for Nelson's syndrome, and three of three for Cushing's disease. There
      was a tendency for a better response rate with a total dose of greater than or
      equal to 50 Gy for prolactinoma. None of the patients were known to develop brain
      necrosis or radiation-induced sarcoma. An analysis of these results and a review
      of the literature is presented here.

PMID- 1987734
TI  - 5-Fluorouracil plus leucovorin in women with metastatic breast cancer. A phase II
      study.
AB  - Because leucovorin increases the antitumor activity of 5-fluorouracil (5-FU) in
      multiple tumor model systems, we performed a clinical trial to evaluate this
      combination in women who had received one or no prior chemotherapy regimens for
      metastatic breast cancer. Thirty-six women with measurable metastatic disease
      were treated with five consecutive days of i.v. leucovorin, 500 mg/m2/day infused
      over 30 min, followed 1 h later by i.v. bolus 5-FU, 375 mg/m2/day. Repeat cycles
      were planned at 4-week intervals. Tumor regression occurred in 10 of 36 patients
      (28%; 95% confidence interval, 14-45%) with a median time to disease progression
      (TTP) of 8.7 months (range 3.2-16.8 months) in the responding patients. The
      median TTP and survival for all patients were 3.0 and 12.4 months, respectively.
      Among 30 patients who had received prior 5-FU, tumor regressions were seen in
      seven (23%; 95% confidence interval 10-42%). The major dose-limiting toxicity in
      this study was mucositis, affecting 89% of the patients. Other toxicities were
      tolerable in the majority of patients. Although the role of leucovorin in breast
      cancer clinical practice remains undefined, the data from this trial support the
      hypothesis that leucovorin enhances the cytotoxic activity of 5-FU against human
      breast cancer.

PMID- 1987735
TI  - Phase II study of aminothiadiazole in advanced squamous cell carcinoma of the
      esophagus.
AB  - Twenty-three patients with advanced inoperable squamous cell carcinoma of the
      esophagus were treated with aminothiadiazole (A-TD) 125 mg/m2 weekly plus
      allopurinol daily in a phase II cooperative group trial. No patients responded to
      treatment; 17 patients progressed, three showed stable disease, and three were
      unevaluable. There were no life-threatening hematologic or metabolic toxicities.
      The median survival from study entry was 5 months. A-TD is not active in advanced
      squamous cell carcinoma of the esophagus.

PMID- 1987736
TI  - Teniposide (VM-26) in patients with advanced endometrial carcinoma. A phase II
      trial of the Gynecologic Oncology Group.
AB  - Twenty-two evaluable patients with advanced endometrial cancer were treated with
      teniposide 100 mg/m2/week administered as a 30-60-minute infusion. Escalations of
      20 mg/m2/week to a maximum dose of 160 mg/m2 were performed in patients without
      toxicity. Seventeen of the 22 patients had prior chemotherapy. Two patients had a
      partial response (95% upper confidence bound for response: 25.9%). Toxicity was
      minimal. Four patients had white blood cell counts of less than 2,000/mm3 but
      only two with less than 1,000/mm3. Only one patient had a platelet count between
      25,000 and 50,000, and no bleeding or septic episodes were noted. Four patients
      had mild nausea, and eight mild nausea and vomiting. Teniposide displays no major
      activity in patients with advanced endometrial cancer who have had prior
      chemotherapy.

PMID- 1987738
TI  - Multiple primary carcinomas as sequelae of treatment of pulmonary tuberculosis
      with repeated induced pneumothoraces. Case report and review of the literature.
AB  - A case is presented of a patient with four separate primary carcinomas (two
      breast, one thyroid, one multiple skin cancers) arising in areas of the body
      subject to repeated low-dose radiation exposure during artificial pneumothorax
      treatment of pulmonary tuberculosis. Evidence for ionizing radiation as the
      likely common etiologic agent for all four tumors is presented and substantiated
      by a review of the literature.

PMID- 1987737
TI  - Weekly epirubicin versus doxorubicin as second line therapy in advanced breast
      cancer. A randomized clinical trial.
AB  - Forty-nine patients with advanced breast cancer who had failed from first-line
      cyclophosphamide, methotrexate, and 5-fluorouracil (CMF regimen) chemotherapy,
      were randomized to treatment with either epirubicin (Epi) or doxorubicin (Dox) at
      a dose of 20 mg/m2 given intravenously (i.v.) weekly to compare the efficacy and
      toxicity of these two anthracyclines given in such a schedule. Of 43 evaluable
      patients 36% (eight of 22) treated with Epi and 38% (eight of 21) treated with
      Dox achieved a complete plus partial response rate (95% confidence limits 16-56%
      +/- 20% and 18-58% +/- 20%, respectively). Patients who obtained a major
      therapeutic response to previous CMF exhibited a significantly higher response
      rate with both the drugs: seven of eight (87.5%) compared with one of 13 (8%); p
      less than 0.05 for Epi and six of seven (86%) compared with two of 15 (13%); p
      less than 0.05 for Dox. The median duration of response was 4.5 months with Epi
      compared with 7 months with Dox, and the median survival of the two groups of
      patients were superimposable (12 months with Epi versus 11 months with Dox). The
      median cumulative dose was 220 mg/m2 (range 160-620) and 240 mg/m2 (range 160
      860) for Epi and Dox, respectively. Gastrointestinal and hematological toxicities
      were moderate for both the drugs, with fewer episodes of nausea and vomiting,
      stomatitis, and leukopenia following Epi administration. A very low incidence of
      alopecia was recorded for both the drugs. Regarding cardiac evaluation, no
      significant differences were evident; however, the only case that developed
      symptomatic congestive heart failure was in the Dox arm, after a cumulative dose
      of 820 mg/m2 at 11.5 months. Epi given weekly at low doses preserves efficacy in
      the treatment of patients with advanced breast cancer, and given at equimolar
      doses, has a slightly better therapeutic index than the parent compound.

PMID- 1987739
TI  - Improved local control of nasopharyngeal carcinoma after intracavitary
      brachytherapy boost.
AB  - In 1976 we began using intracavitary cesium boost technique as a portion of
      comprehensive treatment of primary T2 and T3 nasopharyngeal carcinoma. At first,
      we offered this procedure sporadically to patients with T1 lesions. For the past
      10 years, intracavitary boost has been offered to all patients except those with
      T4 lesions. The radiation therapy program consists of external beam dose of 60-64
      Gy, either once daily (q.d.) or twice daily (b.i.d.) schedule, followed by 10-15
      Gy boost to mucosal surface by intracavitary implant, making a total of
      approximately 75 Gy. This article presents the experience at the Massachusetts
      General Hospital with 146 patients with T1-3 carcinoma of the nasopharynx
      irradiated from 1970 through 1988. Seventy-six patients were treated with
      intracavitary boost and 70 patients were treated up to 65-70 Gy by external beam
      alone. The overall 5-year actuarial local control rate for the T1 lesions was 93%
      after radiation therapy and intracavitary boost as compared with 54% without
      brachytherapy boost (p value = 0.057). For the T1-2 lesions, the corresponding
      local rates after external radiation therapy and brachytherapy boost and after
      external beam irradiation without boost were 90 and 59%, respectively, with p =
      0.001. For the T3 lesions, the rates were 100 and 64%, respectively, with p =
      0.090. The reason for improved local control is unclear and may be due to a
      somewhat higher mucosal dose to the nasopharynx. Hopefully, the improved
      beneficial local control effects may be reflected in improved patient survival.
      However, such data require a controlled randomized clinical trial for
      confirmation.

PMID- 1987740
TI  - High-dose cytosine arabinoside and etoposide in the treatment of relapsed or
      refractory adult leukemia.
AB  - Thirteen patients with leukemia were treated with a combination of cytosine
      arabinoside (ara-C) (3 g/m2 by 1-h infusion every 12 h for 12 doses) and
      etoposide (100 mg/m2 daily over 1 h for 3 doses). Toxicity of the regimen
      consisted of severe hematologic suppression, moderate abdominal colic with
      vomiting and diarrhea, and occasionally severe central nervous system (CNS)
      toxicity. Two patients received the regimen as consolidation for acute
      myelogenous leukemia in remission. Of the remaining 11 patients with chronic
      myeloid leukemia (CML)-blast crises or relapsed/refractory acute myeloid leukemia
      (AML), nine patients (82%) obtained CR (or chronic phase) and two patients
      obtained partial remission (PR). High-dose ara-C and etoposide is an effective
      but toxic regiment for the treatment of relapsed or refractory myeloid leukemias.

PMID- 1987742
TI  - Local-regional recurrences of breast cancer: treatment with radiation therapy and
      local microwave hyperthermia.
AB  - From October 1981 through September 1988, 31 local-regional recurrences of breast
      cancer in 26 patients were treated at the Oncology Center in Trento, Italy, with
      a combination of external radiation therapy (XRT) and superficial local microwave
      hyperthermia (Ht). The mean total XRT dose was 37.40 Gy, ranging from 19.80 to
      60.00 Gy, depending on the extent of previous irradiation. Ht was delivered using
      the same superficial mw applicator, operating at frequencies between 280 and 480
      MHz. The goal was to obtain a minimum intra- and peritumoral temperature of 42.5
      degrees C for 30 min. Ht was applied immediately after XRT, 2 or 3 times per week
      for a total of 1-9 sessions (median 2). Thirty lesions (97%) could be evaluated
      for response 3 months after the end of the combined treatment. Twenty (66.6%)
      complete responses, seven (23.3%) partial responses, and three (10%) with no
      change were observed. No significant acute local side effects were noted, with
      the exception of two thermal burns and one ulceration. Patients achieving
      complete response show actuarial long-term local control of 87.8% at 3 years. In
      our experience, Ht combined with a low/moderate XRT dose may be particularly
      valuable in the palliation of recurrences in previously irradiated regions.
      Excellent response rates can be obtained when Ht is combined with a radical dose
      of irradiation.

PMID- 1987741
TI  - Perceptions of follow-up care in women with breast cancer.
AB  - One hundred one patients with breast cancer, 48 localized and 53 metastatic, were
      questioned about their perceptions of follow-up examinations. Patients with
      metastatic disease preferred more frequent follow-up. Most indicated that they
      wanted their physicians to ask them about pain and nutritional status at each
      follow-up visit and were aware of the tests they had received. Only a third of
      the patients recognized the value of the history in detecting recurrence, and two
      thirds felt that the physical examination was helpful. Laboratory tests and
      imaging procedures were rated higher than the history in detecting recurrence.
      Most patients were unaware of the implications of a normal procedure or test and
      perceived "normal" as meaning an absence of cancer cells in the organ evaluated.
      Knowledge of the value and limitations of testing was not related to educational
      level or disease stage. Patients need to be educated about the effectiveness of
      follow-up examination. Greater emphasis should be placed on the history and
      physical examination, and the limitations of more costly laboratory and imaging
      procedures should be explained carefully.

PMID- 1987743
TI  - Nasopharyngeal carcinoma with bone marrow metastasis.
AB  - Five of 23 patients with recurrent nasopharyngeal carcinoma (NPC) were diagnosed
      to have bone marrow metastasis. They all had advanced local-regional disease, and
      were treated with neoadjuvant chemotherapy and definitive radiotherapy after the
      initial diagnosis. Bone marrow metastasis developed 4-24 months later. The
      clinical features were anemia (5 of 5), leukopenia (3 of 5), thrombocytopenia (4
      of 5), sepsis (3 of 5), tenderness of the sternum (3 of 5), and fever (4 of 5).
      Patients frequently had elevation of serum lactic dehydrogenase (LDH), alkaline
      phosphatase (ALK-P), and IgG and IgA antibody titers to Epstein-Barr viral capsid
      antigen when bone marrow involvement was diagnosed. However, clinical
      manifestations and laboratory tests were not specific. It is important that three
      patients had normal bone scans. All five patients had a rapid downhill course;
      four patients died within 23 days, and the fifth 3 months after the diagnosis of
      bone marrow metastasis. We concluded that bone marrow was a common metastatic
      site in NPC patients. Bone marrow metastasis adversely affected patients'
      survival and required a high index of suspicion for diagnosis. We suggested that
      bone marrow biopsy should be considered as a routine staging procedure in NPC
      patients and indicated especially when patients presented with abnormal blood
      counts, sepsis, bone pain, or tenderness of the sternum. It may be positive in
      the face of a normal bone scan.

PMID- 1987744
TI  - Human lymphoblastoid interferon (IFN-alpha-N1) plus doxorubicin,
      cyclophosphamide, and cisplatin in the treatment of advanced epithelial ovarian
      malignancies. A phase I-II study of the Gynecologic Oncology Group.
AB  - This is a phase I-II study of lymphoblastoid interferon (IFN-alpha-N1) combined
      with primary chemotherapy after cytoreductive surgery in patients with suboptimal
      stage III and stage IV epithelial ovarian carcinoma. Fourteen patients were
      treated initially with cyclophosphamide, doxorubicin, and cisplatin (CAP regimen)
      for two cycles, and IFN (alpha-N1) was added to this combination on day 2 of the
      third cycle. Patients then were divided into four groups, each group receiving
      differing doses of IFN ranging from 3 to 10 MU/m2 on each of days 2-5. A total of
      eight courses of chemotherapy was administered, six of which included interferon.
      Severe fatigue and malaise were the greatest dose-limiting toxicities associated
      with the interferon. However, severe bone marrow suppression also limited the
      administration of interferon. The results of this study suggest that the addition
      of interferon to the multiagent chemotherapy regimen of CAP is both unacceptable
      to patients and excessively toxic to the bone marrow. Because of the small
      patient sample and poor tolerance of the treatment, an accurate evaluation of
      therapeutic response could not be performed.

PMID- 1987745
TI  - Cost savings and microscopic review of cytopenic CSFs.

PMID- 1987746
TI  - Oligoclonal childhood immunoblastic lymphoma.

PMID- 1987747
TI  - Assessment of iron stores in hospitalized patients.

PMID- 1987748
TI  - Flow cytometric DNA analysis of effusions. A new test seeking validation.

PMID- 1987749
TI  - Detection of Ki-67 proliferation rate in breast cancer. Correlation with clinical
      and pathologic features.
AB  - In situ determination of proliferative activity was performed on 203 breast
      cancers by use of Ki-67 monoclonal antibody and immunohistochemical methods.
      Tumor proliferation rate was analyzed and correlated to tumor size and nodal
      status. The relationship between Ki-67 proliferative activity and nuclear
      estrogen receptor content was also investigated on adjacent tissue sections. Ki
      67 values ranged from 1 to 75%, with a median value of 10%. Premenopausal
      patients had greater Ki-67 values (median value, 14.1%) than postmenopausal ones
      (median value, 9.8%). The authors observed no correlation with lymph nodal
      involvement, whereas a statistically significant relationship with tumor size was
      found (P less than 0.01). An inverse correlation (Spearman's coefficient = -0.56;
      P less than 0.001) was seen between Ki-67 values and nuclear estrogen receptor
      content. These results, similar to those reported for other kinetic measurements,
      suggest that in situ detection of Ki-67 proliferation rate is a useful method for
      obtaining cell cycle information. Follow-up studies will be needed to assess an
      eventual prognostic relevance.

PMID- 1987750
TI  - Fluorescent cytochemical detection of estrogen and progesterone receptors in
      breast fine-needle aspirates.
AB  - Estrogen and progesterone receptors were studied in fine-needle aspiration biopsy
      specimens of 56 patients with primary, recurrent, or metastatic breast carcinoma.
      The ligands, 17 B-estradiol-6-carboxymethyloxine-bovine serum albumin fluorescein
      isothiocyanate (FITC-BSA estradiol) and hydroxyprogesterone hemisuccinate bovine
      serum albumin tetramethyl rhodamine isothiocyanate (TMRITC-BSA progesterone),
      were used in the fluorescent cytochemical method. The findings obtained from the
      aspirated cells with the use of the fluorescent cytochemical technique were
      compared with results obtained from the cell population of the same tumor after
      removal with the use of both the fluorescent cytochemical technique and the
      biochemical dextran-coated charcoal (DCC) assay. For the needle aspirates, there
      was 89% concordance for estrogen receptor and 86% concordance for progesterone
      receptor between biochemical and cytochemical results. A high degree of
      correlation was also demonstrated between fine-needle aspirates and imprint
      preparations with the use of the cytochemical technique. This study suggests that
      the fluorescent cytochemical technique is an effective tool in assessment of
      estrogen and progesterone receptor content in fine-needle aspirates of primary
      and metastatic breast cancer. The fluorescent cytochemical technique can be
      performed easily at community hospitals and is well suited for specimens of
      insufficient size for biochemical assay.

PMID- 1987751
TI  - Evaluation of in vitro bromodeoxyuridine labeling of breast carcinomas with the
      use of a commercial kit.
AB  - The prognostic significance of S-phase fraction analyses of breast carcinomas has
      been reported by several investigators. The Cell Proliferation Kit (Amersham
      Corporation, Arlington Heights, IL), which uses in vitro bromodeoxyuridine (BRDU)
      labeling to evaluate cell cycle kinetics without a flow cytometer or
      radioisotopes, simplifies this assay for the clinical-based laboratory by
      providing standardized reagents and recommended methods. This study was performed
      to determine whether data derived from its use were comparable to published S
      phase data from the use of thymidine labeling, BRDU, or other methods on breast
      carcinomas. Primary infiltrating ductal carcinomas (n = 142) and primary lobular
      carcinomas (n = 6) showed mean and median BRDU labeling of 4.63% and 3%, 1.3% and
      1%, respectively, with a range of 0-28%. Benign lesions always had less than 3%
      BRDU uptake (n = 21). Estrogen receptor (ER) and progesterone receptor (PR)
      status correlated with BRDU labeling (P less than 0.05), with the highest S-phase
      fractions in ER- and PR-negative tumors. Correlations between BRDU uptake and
      histologic tumor type or size were observed. Significant correlations between
      BRDU uptake and lymph node status, patient age, or histologic tumor grade were
      not observed. S-phase studies of breast carcinomas using other techniques have
      shown similar data, therefore, the Cell Proliferation Kit appears to be a
      practical and useful method for in vitro S-phase analysis that allows concomitant
      histologic examination of the same tumor tissue sample.

PMID- 1987752
TI  - An unusual venous anomaly of the placenta.
AB  - The authors present an unusual vascular anomaly of the placenta. The placenta was
      very large, weighing 1,490 g. On the fetal surface, numerous dilated and tortuous
      vessels were observed on and under the chorionic membrane, of which three
      branches arose from a vein that was connected to the umbilical vein. One of them
      had a 5 x 2.5 cm aneurysmal dilatation, where three secondary branches arose.
      These venous channels were dilated and tortuous. The longest secondary branch was
      133 cm in length and 1.2 cm in mean diameter and led into the placenta. Multiple,
      severely coiled or straight small branches arising from these vessels were also
      observed as vascular tangles. Some of these smaller vessels also led into the
      placenta. All abnormal vessels were veins. The umbilical cord was also normal
      except for a membranous insertion, and the placenta was unremarkable except for
      its large size.

PMID- 1987753
TI  - Diagnostic value of DNA analysis in effusions by flow cytometry and image
      analysis. A prospective study on 102 patients as compared with cytologic
      examination.
AB  - One hundred twenty-six effusion samples from 102 patients were examined by
      cytology and flow cytometry (FCM). Overall, there was an 84% correlation between
      cytologic and FCM results. Of the 36 malignant cases determined by cytologic
      examination, FCM revealed an aneuploid peak in 20 (56%). Image analysis (IA)
      performed on the malignant cytologic cases with a diploid flow pattern detected
      two additional aneuploid peaks. In addition, FCM indicated three aneuploid cases
      in which cytologic characteristics were initially interpreted as benign (false
      negative). Aneuploidy was therefore detected in 64% of the malignant effusion
      specimens by FCM and IA. Twenty-three of the total of 24 aneuploid cases detected
      by FCM were associated with malignancy (predictive value = 96%). The one
      nonmalignant case was that of hemorrhagic pancreatitis with infected pseudocyst.
      FCM is an excellent tool when moderate to large numbers of tumor cells are
      present, whereas use of IA is advantageous for specimens containing smaller
      numbers of malignant cells because these can be directly analyzed. When an
      aneuploid peak is present, a diagnosis of malignancy must be suspected, and, if
      the initial cytologic screen is negative, a critical review of the cytology
      slides is justified. In those cases with an equivocal atypical cytology report
      and an abnormal cytometric histogram, additional investigation is warranted. In
      some malignancies the tumor cells will be diploid (in this study 36%) and neither
      FCM nor IA will add to tumor detection, leaving cytologic examination as the
      definitive technique.

PMID- 1987754
TI  - An analysis of duplicate testing of prothrombin time and activated partial
      thromboplastin time assays.
AB  - An evaluation of duplicate prothrombin time (PT) and activated partial
      thromboplastin time (aPTT) assays determined by the MCA 110 coagulation analyzer
      was undertaken to develop analytical duplicate performance criteria to quantitate
      the risks associated with single versus duplicate procedures. Included in the
      study were 1,277 patient samples. On the basis of the currently recommended
      therapeutic range for prothrombin ratios, a variation of approximately 10% or
      more between duplicates was considered to be unacceptable. For aPTT assays, the
      recommended therapeutic range for heparin therapy was usually 1.5 to 2.5 times
      the baseline value, and variations of up to 25% might be considered acceptable.
      With these relatively lenient criteria, approximately 2% of PT and 1.3% of aPTT
      assays had differences between duplicate values that were unacceptable. From this
      data the authors concluded that the frequency of errors produced by single
      estimations was too great for satisfactory clinical practice.

PMID- 1987755
TI  - Platelet aggregation in platelet-rich plasma and whole blood in 120 patients with
      myeloproliferative disorders.
AB  - In vitro platelet aggregation in platelet-rich plasma (PRP) and in whole blood
      (WB) was assessed in 31 patients with idiopathic myelofibrosis, 32 with essential
      thrombocytosis, 23 with polycythemia vera, and 34 with chronic myelogenous
      leukemia. In PRP most subjects showed normal or reduced platelet aggregation,
      whereas in WB the majority of patients showed increased platelet function.
      Spontaneous platelet aggregation (SPA) was observed frequently in WB, whereas it
      was seldom observed in PRP. SPA in WB was inhibited by in vitro addition of
      aspirin and apyrase, and SPA was only partially dependent on high platelet count
      because it also occurred in samples with normal platelet content (at variance
      with 13 subjects with reactive thrombocytosis, in which SPA was observed only in
      samples with high platelet concentration). Platelets from patients with
      idiopathic myelofibrosis had the highest tendency to undergo SPA.

PMID- 1987756
TI  - Red cell survival studies in a patient with anti-Tca.
AB  - A radiolabeled, allogenic red cell survival study was performed on a patient who
      lacked the Cromer-related antigen Tca and who had developed the corresponding
      antibody. Red cell survival was 92% at 1 hour and 88% at 24 hours. Monocyte
      monolayer assays (MMA) and IgG subclass determinations were performed on samples
      from: (1) 1965, the period of initial antibody formation; (2) approximately two
      years before the red cell survival study; and (3) four months after the study.
      All samples reacted w+ to 1+ by the antiglobulin test. The earliest sample
      contained IgG1, IgG2, and IgG4 anti-Tca. Because there were 20.5% reactive
      monocytes in the MMA (normal range 0-3%), this antibody may have produced
      extravascular red cell destruction. In contrast to the initial example, the
      samples before and after the red cell survival study both contained IgG2 and IgG4
      subclasses with 1.3% and 2.2% MMA reactivity, respectively. The current pattern
      of antibody subclass, the lack of reactivity in the MMA, and a red cell survival
      of 88% at 24 hours indicate that short-term transfusion support would have been
      well tolerated. This contrasts to the in vitro results obtained with the earliest
      sample, which suggest a clinically significant antibody. This appears to be the
      first report of a red cell alloantibody that remained serologically reactive but
      underwent a loss of its IgG1 fraction, which appeared capable of red cell
      destruction based on the MMA results.

PMID- 1987757
TI  - A rapid, economical, and simple method for concentration of Schistosoma mansoni
      ova in feces.
AB  - An easy, rapid, and economical method for concentration of Schistosoma mansoni
      ova in feces is described. The basic procedure involves 20 minutes of gravity
      sedimentation of a fecal suspension sieved through gauze and suspended in a 5%
      (volume/volume) solution of glycerol in tap water with Ig/L benzoic acid. There
      is excellent recovery of S. mansoni ova. It can be applied under field conditions
      and can be implemented by any laboratory with routine facilities. It also allows
      detection of other ova, larva, and to some extent, cysts.

PMID- 1987758
TI  - Widespread dissemination of Pneumocystis carinii infection in a patient with
      acquired immune deficiency syndrome receiving long-term treatment with
      aerosolized pentamidine.
AB  - Patients with acquired immune deficiency syndrome (AIDS) may be infected with
      many opportunistic pathogens, the most common of which is Pneumocystis carinii.
      P. carinii infection typically presents as a subacute pneumonia. However, rare
      cases of localized, extrapulmonary, and disseminated disease have been described.
      Standard therapy for P. carinii is systemically administered trimethoprim
      sulfamethoxazole or pentamidine. These agents, however, frequently are associated
      with serious adverse effects. More recently, aerosolized pentamidine has been
      proposed as an alternative treatment for those who cannot tolerate standard
      therapy and as primary and secondary prophylaxis. Inhaled pentamidine is
      effective, but it is not without hazards. The authors describe a patient with
      AIDS who received long-term treatment with aerosolized pentamidine and yet died
      as a result of widely disseminated P. carinii infection.

PMID- 1987759
TI  - Expression of blood group antigens H-2, Le(y), and sialylated-Le(a) in human
      colorectal carcinoma. An immunohistochemical study using double-labeling
      techniques.
AB  - In this study, double-labeling immunohistochemistry was used to gain insight into
      the coexpression or interrelationship between blood group antigens (BGA) that are
      differentiation antigens in the normal colon, and BGA that are sequential
      moieties in the same synthetic pathway. Paired-wise Sialylated-Le(a)/Le(y) and H
      2/Le(y) was studied. The Sialylated-Le(a) and Le(y) are synthesized from type 1
      and type 2 backbones, respectively. In the normal colon, the Le(y) and Sialylated
      Le(a) are expressed by cells at the base and surface of the crypt, respectively,
      representing undifferentiated and differentiated enterocytes. The H-2 is
      considered oncofetal in nature, and is considered to be the immediate precursor
      in the synthesis of Le(y). In individual cancers. Sialylated-Lea and Le(y) were
      detected in different cancer cells within the same malignant glands, separately
      in different glands, and in different subcellular compartments of the same cell.
      Both H-2 and Le(y) were coexpressed in the same individual cells in 92% of
      cancers expressing both these BGA. In 50% of the cancers, the H-2 and Le(y) also
      were expressed separately in different malignant glands within individual tumors.
      These findings indicate that, in colorectal cancers, differentiation antigens
      (Sialylated Le(a) and Le(y)) are expressed by different individual cells within
      the same malignant gland somewhat, recapitulating the normal colon crypt.
      Antigens of different backbones occasionally may be expressed in the same cells
      but within different subcellular compartments. Precursor accumulation is common
      in cancers, and antigens in the same synthetic pathway are coexpressed in the
      same cell. The expression of H-2 and Le(y) in different glands (lack of
      coexpression) may be explained possibly by aberrant synthesis of Le(y) by an
      alternate pathway.

PMID- 1987760
TI  - Phenotypic relationships of prostatic intraepithelial neoplasia to invasive
      prostatic carcinoma.
AB  - Thirty-one snap-frozen human prostate specimens containing examples of benign
      hyperplasia, prostatic intraepithelial neoplasia (PIN), and invasive carcinoma
      were analyzed using a panel of 24 antibodies and one lectin. Twenty-seven
      additional routinely processed radical prostatectomy specimens were studied using
      selected probes known to work on formalin-fixed paraffin-embedded material. Three
      probes, anticytokeratin KA4, anti-vimentin V9, and the lectin from Ulex europaeus
      (UEA-1), demonstrated phenotypic similarities between PIN and invasive carcinoma.
      Whereas the luminal cells of normal or hyperplastic prostatic epithelium are
      minimally reactive with KA4 (4%) or UEA-1 (0%) and strongly reactive with anti
      vimentin (91%), both the PIN and invasive carcinoma are reactive with KA4 (89%
      and 93%, respectively) and UEA-1 (96% and 93%, respectively) and minimally
      reactive with anti-vimentin (15% and 0%, respectively). The increased KA4
      staining was shown to be in part due to detection of cytokeratin 19, by using
      cytokeratin-19-specific antibodies, 4.62 and LP2K. The reasons for the increased
      expression of this cytokeratin and the decreased expression of vimentin are
      unclear but seem to indicate a phenotypic relationship between the PIN lesions
      and invasive carcinoma.

PMID- 1987761
TI  - Monoclonal antibodies detect monocyte/macrophage activation and differentiation
      antigens and identify functionally distinct subpopulations of human rheumatoid
      synovial tissue macrophages.
AB  - Monoclonal antibodies (MAbs) to functionally heterogeneous populations of human
      rheumatoid arthritis (RA) synovial tissue macrophages and lipopolysaccharide
      (LPS)-activated U937 cells were generated. These MAbs were used to characterize
      macrophages in situ in the synovial pannus and to study relative antigen
      expression on the surface of cells isolated from the synovium and from normal
      peripheral blood. Monoclonal antibody 3D8, an anti-CD13 MAb, reacts with an
      antigen expressed on the surface of blood monocytes and is a monocyte activation
      related antigen that is upregulated by exposure of monocytes to interferon-gamma
      (IFN-gamma) and LPS. The expression of the 3D8 antigen increases in parallel with
      MHC class II antigen expression and also is upregulated in culture as monocytes
      mature to macrophages. 3D8 antigen is expressed strongly on RA synovial tissue
      lining cells, which are thought to be composed of macrophages. 8D7 antigen
      expression, detected by MAb 8D7, increases on blood monocytes on cellular
      activation with LPS and interferon-gamma, but in contrast to the 3D8 antigen,
      does not increase with monocyte maturation in vitro. The 8D7 antigen is expressed
      differentially on density-defined macrophage subpopulations isolated from RA
      synovial tissue and is expressed more strongly on macrophages that are
      nonangiogenic than those that are angiogenic.

PMID- 1987762
TI  - Dystrophin is required for normal thin filament-membrane associations at
      myotendinous junctions.
AB  - Dystrophin, the deficient gene product in Duchenne muscular dystrophy, is located
      subjacent to the muscle cell membrane at myotendinous junctions, as well as along
      the entire muscle cell. Myotendinous junctions are sites at which thin filaments
      normally are linked to one another and to the cell membrane, by both lateral and
      end-on associations between the thin filaments and membrane. The cell membrane at
      these sites in normal muscle is folded extensively. Dystrophic junctions display
      normal contacts between the ends of thin filaments and subsarcolemmal densities.
      However dystrophic junctions are deficient in lateral associations between thin
      filaments and the membrane and display less membrane folding than controls. These
      structural defects would result in stress concentrations at sites of thin
      filament attachment to the membrane, which can cause membrane tearing during
      muscle activation, especially in large-diameter and mature muscle cells. This
      deficiency in dystrophic myotendinous junction structure may contribute to our
      understanding of previously unaccountable aspects of the etiology of Duchenne
      muscular dystrophy.

PMID- 1987763
TI  - Expression of IgG Fc receptor antigens in placenta and on endothelial cells in
      humans. An immunohistochemical study.
AB  - Expression of leukocyte IgG Fc receptor (Fc gamma R) antigens by placenta,
      endothelial cells (EC) of normal tissues, and ECs of kidney and skin from
      subjects with immune complex diseases was studied immunohistochemically using
      anti-Fc gamma R monoclonal antibodies (MAb). Monoclonal antibodies against all
      three leukocyte Fc gamma R classes stained placental villous macrophages.
      Placental villous trophoblasts were stained intensely by anti-Fc gamma RIII MAb
      3G8, while both anti-Fc gamma RI (MAb 32) and anti-Fc gamma RII MAbs IV3, KU79,
      CIKM5, 2E1, KB61, and 41H16) antibodies did not react with these cells. Anti-Fc
      gamma RII MAbs IV3, KU79, CIKM5, 2E1, KB61, and 41H16 immunostained placental
      villous capillary EC, in contrast to anti-Fc gamma RI MAb 32 and anti-Fc gamma
      RIII MAb 3G8, CLB-Granl, and B73.1, which did not bind. Anti-Fc gamma RI MAb 32,
      anti-Fc gamma RII MAb IV3 and CIKM5, and anti-Fc gamma RIII MAb 3G8 did not react
      with the ECs of tonsil, liver, kidney, spleen, intestine, lung, or uterus.
      Similarly no EC staining was seen with these four MAbs in 14 skin and 14 kidney
      biopsies from subjects with immune-complex diseases. Fc gamma R antigens are
      expressed constitutively only by placental villous ECs and are not induced on
      nonplacental ECs by immune-complex-mediated diseases.

PMID- 1987764
TI  - Anatomic pathway of pulmonary fluid leakage in endotoxemia induced in rats. The
      red blood cell packing method and its application.
AB  - The anatomic site of pulmonary fluid leakage in endotoxemia in rats was
      investigated using the red blood cell packing method and low-dose horseradish
      peroxidase as a tracer. To differentiate between arterioles and venules in a
      given section by light and electron microscopy, human red blood cells fixed with
      4% paraformaldehyde were administered to the rat pulmonary arterial trunk at a
      pressure of 40 cm water. Fixed red blood cells were packed in the lumina of
      arteries, arterioles, and a few capillaries surrounding arterioles, while veins,
      venules, and almost all capillaries were void of red blood cells in the lumina.
      Fifteen minutes after the intravenous administration of 3 and 30 mg/kg of
      Escherichia coli endotoxin, extravascular leakage of horseradish peroxidase from
      venules (nonmuscular veins) was evident. Two hours after the intravenous
      injection of the same doses of endotoxin, some arterioles (nonmuscular arteries)
      and venules (non-muscular veins) showed extravascular leakage of horseradish
      peroxidase, while few capillaries showed this leakage. These results suggest that
      pulmonary fluid leakage occurs predominantly through venules in the early phase
      of endotoxemia (at 15 minutes), while the arterioles contribute to fluid leakage
      in addition to venules in the late phase of endotoxemia (at 2 hours).

PMID- 1987765
TI  - Effects of smoke inhalation on surfactant phospholipids and phospholipase A2
      activity in the mouse lung.
AB  - The effects of smoke inhalation on the pulmonary surfactant system were examined
      in mice exposed for 30 minutes to smoke generated from the burning of
      polyurethane foam. At 8 or 12 hours after exposure, surfactants were isolated
      separately from lung lavage (extracellular surfactant) and residual lung tissue
      (intracellular surfactant) for phospholipid analysis. Calcium-dependent
      phospholipase A2 (PLA2) was measured on a microsomal fraction prepared from the
      tissue homogenate. Smoke inhalation produced a twofold increase in extracellular
      surfactant total phospholipid. While there was no change in the total
      phospholipid or phosphatidylcholine (PC) content of the intracellular surfactant,
      smoke inhalation significantly decreased the disaturated species of PC (DSPC).
      The specific activity of PLA2 was reduced by more than 50% in both groups of
      exposed mice. Smoke inhalation appears to result in selective depletion of the
      DSPC of intracellular surfactant and PLA2 involved in its synthesis. This
      depletion may be compensated for by increased secretion or slower breakdown of
      the material present in the extracellular compartment.

PMID- 1987766
TI  - Urinary excretion of the C5b-9 membrane attack complex of complement is a marker
      of immune disease activity in autologous immune complex nephritis.
AB  - The urinary excretion of the C5b-9 membrane attack complex of complement
      correlates with glomerular deposition of antibody in the passive Heymann
      nephritis (PHN) model of membranous nephropathy (MN). To determine if this
      parameter can be correlated with antibody deposition in a model of MN induced by
      an autologous mechanism and thus more analogous to human MN, the relationship of
      urinary C5b-9 to ongoing glomerular immune complex formation late in autologous
      immune complex nephritis (AICN) was studied. Based on urinary C5b-9, the animals
      were divided into two groups at 12 weeks after induction of AICN, those with
      persistently high urinary C5b-9 excretion and those in whom urinary excretion of
      C5b-9 returned to undetectable levels. While all rats developed glomerular
      deposition of rat IgG and significant proteinuria, high C5b-9 excretors had
      greater proteinuria and prolonged positive staining for glomerular C3. When
      normal syngeneic kidneys were transplanted into rats (n = 3) from each group,
      only those with persistent C5b-9 excretion developed subepithelial immune
      deposits of rat IgG in the transplanted kidney. As in the PHN model of MN,
      proteinuria was dissociated widely from urinary C5b-9 excretion, glomerular C3
      staining, and evidence of circulating antibody. Thus these findings demonstrate
      that urinary excretion of C5b-9 serves as an index of on-going immunologic
      disease activity in the AICN model of MN, while proteinuria does not.

PMID- 1987767
TI  - Tumor-secreted vascular permeability factor increases cytosolic Ca2+ and von
      Willebrand factor release in human endothelial cells.
AB  - Vascular permeability factor (VPF), a tumor-secreted heparin-binding protein (Mr
      approximately 38,000), is responsible for increased vessel permeability and fluid
      accumulation associated with tumor growth. Vascular permeability factor also
      promotes the growth of human umbilical vein endothelial cells (EC) and bovine
      pulmonary ECs in vitro. It is shown for the first time that guinea pig VPF (half
      maximal and maximal dose approximately 0.4 and 22 pmol/l (picomolar),
      respectively), as well as human VPF, are potent stimuli for human ECs resulting
      in [Ca2+]i increases (maximal three- to fourfold) and inositol triphosphate (IP3)
      formation. Unlike the maximal responses to thrombin and histamine, the [Ca2+]i
      response to a maximal VPF dose was preceded by a characteristic 10- to 15-second
      delay. Guinea pig VPF also selectively increased [Ca2+]i in cultured aortic and
      pulmonary artery ECs, but not aortic smooth muscle cells, human fibroblasts, or
      neutrophils. Affinity-purified rabbit antibody (raised to a synthetic peptide
      representing VPF N-terminal amino acids 1 to 24) adsorbed all vessel permeability
      increasing activity, EC growth-promoting activity, and specifically all activity
      responsible for increasing EC [Ca2+]i. Similar to other mediators that increase
      [Ca2+]i in cultured ECs, VPF also induced a 200% increase in von Willebrand
      factor release. Together these data indicate that VPF acts directly on ECs and
      that rapid cellular events in its in vivo/in vitro actions are likely to involve
      phospholipase C activation, [Ca2+]i increase, and von Willebrand factor release.

PMID- 1987768
TI  - Transforming growth factor-beta production in anti-glomerular basement membrane
      disease in the rabbit.
AB  - The purpose of this study was to assay for the presence of collagen synthesis
      stimulatory activity in the kidney during immune-induced renal injury that
      results in severe fibrosis in both glomerular and interstitial compartments. A
      model of antiglomerular basement (anti-GBM) disease in the rabbit was induced on
      day 0 by the injection of anti-GBM antibody and renal cortex tissues were then
      sampled at various time points. Only conditioned media prepared from diseased
      renal cortical samples showed collagen synthesis stimulatory activity when tested
      on rabbit mesangial cells. The activity had an estimated molecular weight range
      of 16 to 25 kd and was neutralized by antibody to transforming growth factor-beta
      (TGF-beta). A standard assay for TGF-beta using a mink lung epithelial cell line
      confirmed the increase in TGF-beta activity in conditioned media of diseased
      cortex from day 7 and day 14 animals, which was not significantly activated by
      previous acidification. This suggests that most of the TGF-beta present in renal
      conditioned media was in the active form. The increase in renal cortical
      secretion of active TGF-beta was accompanied by increases in renal cortical TGF
      beta mRNA content on days 4 and 7 after induction, with subsequent return to
      control levels. A similar increase in TGF-beta activity was present in
      nonacidified conditioned media of purified glomeruli from diseased days 7 and 14
      animals, which was also accompanied by significant increases in TGF-beta mRNA.
      However with acidification no significant differences were noted between control
      and diseased samples, suggesting the presence of substantial latent TGF-beta
      activity in control glomerular conditioned media. These same control-conditioned
      media contained inhibitor activity for added exogenous TGF-beta. These results
      support the conclusion that the association between increased TGF-beta secretion
      and increased renal cortical collagen synthesis in this model is consistent with
      a role for this cytokine in directing fibrogenesis in the kidney.

PMID- 1987769
TI  - Diffuse lymphocyte-predominant Hodgkin's disease (diffuse paragranuloma). A
      variant of the B-cell-derived nodular type.
AB  - Lymph node sections from 10 cases of mixed nodular/diffuse and 10 cases of
      completely diffuse lymphocyte-predominant Hodgkin's disease (LPHD) were
      immunophenotyped. The results obtained were compared with those of nodular LPHD
      (nodular paragranuloma). In conventional stains, nodular/diffuse LPHD differed
      from diffuse LPHD in the presence of nodularity, which can be best demonstrated
      with silver impregnation. Immunohistologic analysis showed a correlation of the
      difference in nodularity with the presence or absence and pattern of follicular
      dendritic cell (FDC) meshwork, ie, a relatively sharply defined and large
      spherical meshwork was present in nodular areas of nodular/diffuse LPHD, whereas
      FDCs were either absent or present in a diffuse, ill-defined meshwork, usually of
      small size, in the diffuse zones of nodular/diffuse LPHD and in diffuse LPHD. The
      amount of FDC meshwork corresponded roughly to the number of reactive B cells and
      T cells, meaning that in diffuse areas significantly fewer B cells and more T
      cells were observed than in nodular areas. The immunohistologic analysis also
      showed that the antigen profile (positivity with the monoclonal B-cell marker L26
      in the majority [14/20] of cases and negativity for CD15 in all but one of 20
      cases) of the tumor cells in both nodular/diffuse LPHD and diffuse LPHD were
      comparable while it was different from the antigen profile (L26- and CD15+) in
      most cases of nodular sclerosis and mixed cellularity types of HD. This suggests
      that the considered subtypes of LPHD differ mainly in FDC pattern, but not in
      origin and nature of the tumor cells. This further justifies assignment of the
      above-mentioned LPHD subtypes to the category paragranuloma (LPHD).

PMID- 1987771
TI  - Fibroblast growth factor gene expression in AIDS-Kaposi's sarcoma detected by in
      situ hybridization.
AB  - Biopsy samples from five acquired immune deficiency syndrome (AIDS)-Kaposi's
      sarcomas and one non-AIDS-associated Kaposi's sarcoma were assayed by in situ RNA
      hybridization onto paraformaldehyde-fixed, paraffin-embedded skin sections for
      the presence of two fibroblast growth factor gene transcripts, FGFB and FGF5.
      FGF5 gene expression was detected in the characteristic Kaposi's sarcoma spindle
      shaped cells in the five samples from human immunodeficiency-positive (HIV+)
      patients. FGFB transcripts were detected in Kaposi's sarcoma cells as well as in
      epidermis of HIV- and HIV+ patients. These results complement the observations
      about growth factor gene expression done on Kaposi's sarcoma-derived cell lines,
      which thus appear to be representative of what happens in vivo. Furthermore, they
      demonstrate a contrasting expression pattern of FGF5 and FGFB genes, both
      involved in the growth factor pathogenic cascade leading to Kaposi's sarcoma.

PMID- 1987770
TI  - Mature eosinophils stimulated to develop in human cord blood mononuclear cell
      cultures supplemented with recombinant human interleukin-5. Part I. Piecemeal
      degranulation of specific granules and distribution of Charcot-Leyden crystal
      protein.
AB  - Human cord blood mononuclear cells were cultured for 35 days in media containing
      recombinant human interleukin 5 (rhIL-5) supplemented with a fraction of the
      culture supernatant of phytohemagglutinin (PHA)-stimulated human T lymphocytes
      from which interleukin 2 (IL-2) was eliminated. Cultured cells were studied by
      electron microscopy and an immunogold procedure to detect subcellular site(s) of
      Charcot-Leyden crystal (CLC) protein. The majority of cells (greater than 70%)
      developing in this system were mature eosinophils, with descending frequency of
      other cells, including macrophages, mature basophils, eosinophilic myelocytes,
      and mature neutrophils. Mature eosinophils were characterized by increased
      numbers of primary granules, small granules, tubulovesicular structures, and
      decreased secondary granules. These eosinophils showed extensive piecemeal
      degranulation (PMD) characterized by partially empty and empty secondary granule
      chambers in the cytoplasm. Small, smooth vesicles were evident within empty
      granule chambers as well as adjacent to them. Eosinophils formed close
      associations with phagocytic macrophages that contained both standard-shaped and
      irregularly shaped CLC within phagolysosomes. Subcellular sites of CLC protein
      were demonstrated by immunogold in eosinophils and macrophages arising in these
      cultures. Charcot-Leyden crystal protein was present in the nuclear matrix and
      extraorganellar cytoplasm of eosinophils. Primary granules and some cytoplasmic
      vesicles were labeled for CLC protein, but full and empty secondary granules and
      the extensive network of tubulovesicles were not. Charcot-Leyden crystals were
      absent from eosinophils, nor were they present in the extracellular space.
      Charcot-Leyden crystals were absent from eosinophils, nor were they present in
      the extracellular space. Charcot-Leyden crystals within phagosomes of macrophages
      were labeled by the immunogold procedure for CLC protein. These results
      demonstrate that rhIL-5-supplemented, PHA-stimulated, T-cell-conditioned media
      induced the development of mature human eosinophils from cord blood cells. These
      eosinophils underwent PMD of secondary granule contents. Immunogold analysis
      showed eosinophil CLC protein in the cytoplasm, nucleus, and primary granules of
      eosinophils. Macrophages also were present in these cultures. They contained CLC
      protein-containing crystals in their phagosomes, suggesting active sequestration
      of eosinophil CLC protein by macrophages in vitro.

PMID- 1987772
TI  - Effects of recombinant tumor necrosis factor-alpha on cultured pulmonary artery
      and lung microvascular endothelial monolayers.
AB  - Whole animal studies suggest that tumor necrosis factor-alpha (TNF alpha) plays a
      central role in the endotoxin response. In vitro studies show that TNF alpha and
      endotoxin induce a similar range of metabolic changes to endothelial cells.
      However both endotoxin- and TNF alpha-induced cytotoxicity is not a feature of
      all endothelial cells lines. In recent studies, the authors have shown that
      endotoxin causes different responses in endothelial cells taken from two levels
      of the lung's circulation--main pulmonary artery and lung microvasculature.
      Endotoxin exposure caused cell death for cells cultured from the large pulmonary
      artery but not for those taken from lung periphery. The present study examined
      the effect of TNF alpha on endothelial cells cultured from two levels of the
      lungs' circulation--the main pulmonary artery and the lung microvasculature. End
      points examined included lactate dehydrogenase (LDH), prostacyclin, and
      prostaglandin E2 (PGE2) release and phase contrast microscopy. Exposure to TNF
      alpha resulted in a dose-dependent increase in LDH release and number of detached
      cells for cells of the pulmonary artery, whereas cells from the microvasculature
      seemed unaffected. At both levels, however, TNF alpha caused increased release of
      both prostacyclin and PGE2. The authors conclude that TNF alpha causes different
      effects in endothelial cells cultured from two levels of the same organ.

PMID- 1987773
TI  - Relationship between vasopressin-sensitive water transport and plasma membrane
      fluidity in kidney collecting tubule.
AB  - The role of plasma membrane fluidity in the regulation of kidney tubule water
      permeability has been uncertain. We have used new methods to image the
      fluorescence anisotropy of fluidity-sensitive fluorophores (Fushimi, Dix, and
      Verkman. Biophys. J. 57: 241-254, 1990) to quantitate membrane fluidity in cells
      of the vasopressin-sensitive cortical collecting tubule (CCT) and water
      impermeable cortical thick ascending limb (CTAL). Isolated tubule segments from
      rabbit kidney were perfused in vitro, and apical or basolateral plasma membranes
      were stained with trimethylammonium diphenylhexatriene (TMA-DPH). TMA-DPH
      anisotropy (r) was imaged quantitatively by an epifluorescence microscope
      equipped with rotatable polarizers; TMA-DPH nanosecond lifetime (tau) was
      measured by flash-lamp excitation and gated photomultiplier detection. In CCT,
      apical membrane r (0.254 +/- 0.003) was similar to basolateral r (0.252 +/-
      0.005). Serosal vasopressin at a dose that increased water permeability greater
      than 10-fold (250 microU/ml) did not affect apical membrane r (delta r = 0.002 +/
      0.003; 7 tubules). A 0.002 change in r was less than that produced by a 2
      degrees C temperature variation. In CTAL, apical membrane r was 0.249 +/- 0.002,
      similar to r from basolateral membrane of proximal tubule (0.24), but much less
      than that of proximal tubule apical membrane (0.29). These results establish
      methodology to quantitate fluidity in intact kidney tubule segments and provide
      the first measurements of plasma membrane fluidity in CTAL and CCT. Our results
      suggest that regulation of bulk membrane fluidity in CCT apical membrane is not a
      component of the hydrosmotic action of vasopressin and that low apical membrane
      fluidity is not responsible for the low water and NH3 permeabilities in CTAL.

PMID- 1987774
TI  - Regulation of cellular volume in rabbit ventricular myocytes: bumetanide,
      chlorothiazide, and ouabain.
AB  - Video microscopy was used to study the regulation of cell volume in isolated
      rabbit ventricular myocytes. Myocytes rapidly (less than or equal to 2 min)
      swelled and shrank in hyposmotic and hyperosmotic solutions, respectively, and
      this initial volume response was maintained without a regulatory volume decrease
      or increase for 20 min. Relative cell volumes (normalized to isosmotic solution,
      1T) were as follows: 1.41 +/- 0.01 in 0.6T, 1.20 +/- 0.04 in 0.8T, 0.71 +/- 0.04
      in 1.8T, and 0.57 +/- 0.03 in 2.6T. These volume changes were significantly less
      than expected if all of the measured volume was osmotically active water. Changes
      in width and thickness were significantly greater than changes in cell length.
      The idea that cotransport contributes to cell volume regulation was tested by
      inhibiting Na(+)-K(+)-2Cl- cotransport with bumetanide (BUM) and Na(+)-Cl-
      cotransport with chlorothiazide (CTZ). Under isotonic conditions, a 10-min
      exposure to BUM (1 microM), CTZ (100 microM), or BUM (10 microM) plus CTZ (100
      microM) decreased relative cell volume to 0.87 +/- 0.01, 0.86 +/- 0.02, and 0.82
      +/- 0.04, respectively. BUM plus CTZ also modified the response to osmotic
      stress. Swelling in 2.6T medium was 76% greater and shrinkage in 0.6T medium was
      29% less than in the absence of diuretics. In contrast to the rapid effects of
      diuretics, inhibition of the Na(+)-K+ pump with 10 microM ouabain for 20 min did
      not affect cell volume in 1T solution. Nevertheless, ouabain decreased swelling
      in 0.6T medium by 52% and increased shrinkage in 1.8T medium by 34%. These data
      suggest that under isotonic conditions Na(+)-K(+)-2Cl- and Na(+)-Cl- cotransport
      are critical in establishing cell volume, but osmoregulation can compensate for
      Na(+)-K+ pump inhibition for at least 20 min. Under anisotonic conditions, the
      Na(+)-K+ pump and Na(+)-K(+)-2Cl- and/or Na(+)-Cl- cotransport are important in
      myocyte volume regulation.

PMID- 1987775
TI  - Internal alkalinization by reversal of anion exchange in human neutrophils:
      regulation of transport by pH.
AB  - When steady-state human neutrophils bathed in 148 mM Cl- are transferred to a Cl(
      )-free medium containing 0.5 mM HCO3- and 148 mM glucuronate or aspartate as
      nominally inert replacement ions, there is a rapid efflux of 36Cl- from the
      cells. The accelerated loss of Cl- is accompanied by an intracellular
      alkalinization of 0.7-0.9 pH units. Both the Cl- efflux and intracellular pH
      (pHi) transient are dependent on extracellular HCO3- and are sensitive to
      inhibition by SITS and alpha-cyano-4-hydroxycinnamate, which block anion
      exchange, thereby indicating that these processes are due to the countertransport
      of internal Cl- for external HCO3-. Rate of anion exchange is strongly influenced
      by pH, which functions to regulate carrier activity; alkalinization stimulates
      the transport velocity, whereas acidification inhibits it. The relationship to
      pHi follows a Hill equation with pK' approximately 7.40 and Hill coefficient of
      3.3, thereby suggesting that approximately 3 HCO3- may be required to bind to the
      modifier site. Neutrophils placed in glucuronate medium progressively shrink
      during the first 7.5 min of incubation due to the net loss of osmotically active
      particles through Cl(-)-HCO3- exchange. However, between 7.5 and 30 min, cells
      regain their normal cell size. This volume recovery phase correlates with the
      time course of 22Na+ and [14C]glucuronate influxes, whose kinetics can be
      dissociated from that of anion exchange. Uptake of glucuronate is largely Na+
      dependent (whereas Cl(-)-HCO3- exchange is not), is resistant to amiloride, and
      can be blocked by furosemide, which suggests that glucuronate probably enters via
      a volume-activated pathway such as Na+ + glucuronate cotransport.

PMID- 1987776
TI  - Regulation of cytosolic pH of cultured mesangial cells by prostaglandin F2 alpha
      and thromboxane A2.
AB  - Prostaglandins (PG) and thromboxane A2 (TxA2) have marked vasoactive effects on
      the renal glomerular microcirculation. Exposure of cultured mesangial cells to
      PGF2 alpha and TxA2 mimetics results in a rapid elevation of free cytosolic Ca2+
      ([Ca2+]i) followed by contraction and cell proliferation. We studied whether
      other ionic changes mediate these effects of eicosanoids on cells of rat and
      human origin. Cytoplasmic pH (pHi) was monitored in cells loaded with the
      fluorescent, intracellularly trapped pH-sensitive probe 2',7'-bis(carboxyethyl)
      5,6-carboxyfluorescein. PGF2 alpha in rat cells and the TxA2 mimetic U-46619 in
      human cells induced rapid, dose-dependent cytosolic acidification followed by
      recovery and net alkalinization mediated by enhanced Na(+)-H+ exchange. The early
      acidification was also stimulated by ionomycin and Ca2(+)-mobilizing peptides,
      implicating a Ca2(+)-dependent mechanism. Alkalinization was abolished by removal
      of extracellular Na+ and by amiloride. Both components of the responses were
      inhibited by phorbol myristate acetate, which could mimic alkalinization,
      suggesting a regulatory role of protein kinase C in activation of the Na(+)-H+
      exchanger by eicosanoids. Vasoconstrictor arachidonate metabolites may control
      glomerular cell function by a signaling mechanism centered on concurrent changes
      of pHi and [Ca2+]i.

PMID- 1987777
TI  - Luminescence of luciferin-luciferase microinjected into Limulus ventral
      photoreceptors may not reflect the intracellular ATP level.

PMID- 1987778
TI  - Water and urea permeability properties of Xenopus oocytes: expression of mRNA
      from toad urinary bladder.
AB  - The Xenopus oocyte was evaluated as an mRNA expression system for water and urea
      transporters. Osmotic water permeability (Pf) was measured from the time course
      of oocyte volume in response to osmotic gradients using a real-time imaging
      method. Diffusional water permeability (Pd) was measured by 3H2O efflux. In
      mature oocytes treated with collagenase to remove the follicular cell layer, Pf
      was 8.6 +/- 0.6 x 10(-4) (SD) cm/s (n = 32) at 25 degrees C and independent of
      the time after oocyte removal (0-8 days). The activation energy (Ea) for Pf was
      10.2 kcal/mol (10-32 degrees C). Pf was independent of osmotic gradient size (50
      200 mosmol) in swelling experiments but decreased in an unpredictable manner in
      shrinking experiments. Pf was not altered by removal of the vitelline membrane
      but was decreased by 75% when the follicular cell layer was intact. In
      collagenase-treated oocytes, amphotericin (0-500 micrograms/ml) increased Pf from
      8 x 10(-4) to 84 x 10(-4) cm/s in a dose-dependent manner. Pd was 3.4 +/- 0.2 x
      10(-4) (SE) cm/s at 25 degrees C, 1.5 +/- 0.2 x 10(-4) cm/s at 4 degrees C, and
      5.1 +/- 0.5 x 10(-4) cm/s at 25 degrees C in the presence of 500 micrograms/ml
      amphotericin; Ea was 6.5 kcal/mol. Thus Pd, but not Pf, is unstirred layer
      limited.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1987779
TI  - Regulation of calcium-activated potassium efflux by neurotensin and other agents
      in HT-29 cells.
AB  - Neurotensin receptors have been shown previously to be coupled to
      polyphosphoinositide turnover and intracellular Ca2+ ([Ca2+]i) mobilization in HT
      29 colonic epithelial cells (Bozou et al. Biochem. J. 264: 871, 1989; Turner et
      al. J. Pharmacol. Exp. Ther. 253: 1049, 1990). In this study, neurotensin was
      found to enhance dramatically the Ba2(+)- and tetraethylammonium chloride
      sensitive K(+)-efflux rate (measured with 86Rb+) in the presence of ouabain and
      bumetanide, with basal efflux increasing 4.5 +/- 0.5-fold with 10 nM neurotensin.
      The K(+)-efflux rate, which was partially dependent on the extracellular Ca2+
      concentration, was also increased by carbachol and ATP, two other [Ca2+]i
      mobilizing agonists in HT-29 cells, as well as by the Ca2+ ionophores ionomycin
      and A23187, suggesting that the efflux was through Ca2(+)-activated K+ channels.
      Pretreatment of cells with neurotensin, carbachol, or ATP desensitized subsequent
      neurotensin-stimulated efflux by 82, 57, and 63%, respectively, confirming our
      previous results which indicated homologous and heterologous desensitization of
      the neurotensin receptor-signal transduction pathway. Pretreatment of cells with
      the protein kinase C activators phorbol 12-myristate 13-acetate (PMA) and
      mezerein did not affect [Ca2+]i mobilization or K+ efflux directly but
      desensitized neurotensin-stimulated efflux by greater than 80%. Pretreatment (2
      h) with PMA also decreased K+ efflux in response to ionomycin by 59%, although
      ionomycin-induced [Ca2+]i mobilization was not inhibited. Downregulation of
      protein kinase C by overnight pretreatment with PMA resulted in recovery of
      ionomycin-stimulated efflux. These results suggest that agonist-stimulated Ca2(+)
      activated K+ channels in HT-29 cells are regulated at multiple steps in the
      signal transduction pathway.

PMID- 1987780
TI  - Effect of low-density lipoprotein on endothelial cell membrane fluidity and
      mononuclear cell attachment.
AB  - To determine the effects of prolonged low-density lipoprotein (LDL) exposure in
      vitro on cultured endothelial cell (EC) lipid dynamics and cellular function,
      human umbilical vein ECs were incubated in LDL concentrations [cholesterol (Chol)
      = 240 mg/dl] associated with the premature development of atherosclerosis. After
      4 days of incubation, cells were examined for changes in cellular lipid
      composition and for membrane fluidity. Results indicate that LDL-EC have
      increased Chol content (control EC vs. LDL-EC = 22.4 +/- 5.26 vs. 38.9 +/- 0.24
      nmol/10(6) cells, P less than 0.05) and cellular Chol-to-phospholipid ratio (0.61
      +/- 0.10 vs. 1.21 +/- 0.10 mol/mol, P less than 0.05). Augmentation of EC Chol
      content was accompanied by a marked decrease in EC cellular membrane fluidity as
      assessed by fluorescence polarization (anisotropy, r values, 0.172 +/- 0.019 vs.
      0.226 +/- 0.014, P less than 0.0001). LDL-induced changes in EC lipid dynamics
      were associated with enhanced EC binding of monocytes (P less than 0.05) and U937
      cells (P less than 0.01). Both LDL-induced decreases in membrane fluidity and
      enhanced attachment of mononuclear cells were reversed to control levels
      following a 2-min incubation of LDL-EC with the membrane mobility agent, A2C.
      These data therefore suggest that LDL-induced modulations in lipid dynamics play
      an important role in perturbation of EC function.

PMID- 1987781
TI  - Sepsis does not impair tricarboxylic acid cycle in the heart.
AB  - Sepsis has been reported to cause mitochondrial dysfunction and inhibition of key
      enzymes that regulate the tricarboxylic acid (TCA) cycle. We investigated the
      effect of sepsis on high-energy phosphates, glycolytic and TCA cycle
      intermediates, and specific amino acids that are involved in regulating the size
      of the TCA cycle pool during changes in metabolic state of the heart. Sepsis was
      induced in 12 female rats by the cecal ligation and perforation technique under
      halothane anesthesia; seven control rats underwent cecal manipulation without
      ligation. At 36-42 h postsurgery, the rats were reanesthetized, the chest was
      opened, and the hearts were freeze-clamped. Perchloric acid extracts of the
      hearts were analyzed with fluorometric enzymatic methods and 31P nuclear magnetic
      resonance spectroscopy. There were no significant differences in the levels of
      the TCA cycle intermediates or high-energy phosphates between the septic and
      control rats. The major metabolic changes were the 28% decrease in alanine and
      the 31% decrease in glutamate in the septic hearts compared with control (P less
      than 0.05 and P less than 0.005, respectively). Phosphocholine, a component of
      membrane phospholipids, was increased by 91% in the septic hearts (P less than
      0.01). We conclude that sepsis does not impair the TCA cycle or induce
      significant cellular ischemia in the heart. The increase in phosphocholine may
      represent significant cellular membrane disruption during sepsis.

PMID- 1987783
TI  - Neuromuscular adaptations to cross-reinnervation in 12- and 29-mo-old Fischer 344
      rats.
AB  - The aim was to test hypotheses regarding the adaptive response of the extensor
      digitorum longus (EDL) muscle of 12- and 29-mo rats following denervation and
      cross-reinnervation by the soleus nerve. The mass of cross-reinnervated EDL
      muscle was 87 and 86% of self-reinnervated control values in 12-mo (99 +/- 3 mg)
      and 29-mo (74 +/- 3 mg) rats, respectively. Cross-reinnervated EDL fiber area was
      56 and 67% of self-reinnervated values in 12-mo (1,733 +/- 253 microns 2) and 29
      mo (1,264 +/- 71 microns 2) rats, respectively. Cross-reinnervation increased the
      density of neural contact 26% in 12-mo rats and decreased density by 50% in 29-mo
      animals. In 12-mo rats 17% of motor end plates (MEP) were void of terminal nerves
      following cross-reinnervation compared with 48% in 29-mo rats. In cross
      reinnervated muscles, slow myosin heavy chain (MHC) was 65 +/- 9 and 25 +/- 3% of
      total MHC in 12- and 29-mo rats, respectively. The percentage of type I fibers
      derived histochemically was 65 +/- 8% in 12-mo rats and 18 +/- 1% in 29-mo rats.
      In conclusion, there is an age-associated decrease in the ability of neurons to
      reinnervate the MEP area after nerve section. The conversion of fiber type in
      innervated fibers in response to cross-reinnervation may not differ due to age.

PMID- 1987782
TI  - Prolonged incubation of skeletal muscle increases system A amino acid transport.
AB  - During the course of experiments involving prolonged incubation of skeletal
      muscle, we observed large increases in system A amino acid transport activity.
      System A activity was monitored with the nonmetabolizable amino acid analogue
      alpha-(methylamino)isobutyrate (MeAIB). When rat epitrochlearis muscles are
      incubated in Krebs-Henseleit buffer supplemented with 0.1% bovine serum albumin
      and 8 mM glucose, basal MeAIB transport doubles after 5 h and is elevated
      approximately sevenfold after 9 h compared with rates measured in muscles
      incubated for 1 h. Insulin-stimulated transport also doubles after 5 h and
      increases by fourfold after 9 h. The increases in basal and insulin-stimulated
      system A transport over time can be prevented by incubating muscles in the
      presence of cycloheximide. Addition of minimum essential medium essential amino
      acids (EAA) to the incubation medium blocks the increase in basal and insulin
      stimulated MeAIB transport measured after 9 h by 85-90 and 60%, respectively. A
      single amino acid, glutamine, can account for half of the inhibitory effect of
      EAA on the time-dependent increase in basal system A transport. Amino acid
      metabolism is not necessary for inhibition of the rise in basal MeAIB transport.
      At concentrations normally present in minimum essential medium, nonessential
      amino acids are less effective (51% inhibition) in preventing the rise in basal
      transport occurring over 9 h. At three times normal concentrations, however, the
      ability of nonessential amino acids to prevent the time-dependent increases in
      basal and insulin-stimulated MeAIB transport is comparable to that of EAA. These
      changes in MeAIB transport with prolonged incubation are not due to muscle
      deterioration.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1987784
TI  - Temporal structure of in vivo growth hormone secretory events in humans.
AB  - The time course of spontaneous growth hormone (GH) secretion was studied in 12
      normal men by analyzing serum GH concentrations measured in blood collected at 5
      min intervals over 24 h with a multiple-parameter deconvolution model to
      simultaneously resolve endogenous GH secretory and clearance rates. Twenty-four
      hour profiles of serum GH concentrations were accounted for by an average of 12
      +/- 1.2 (SE) discrete GH secretory bursts having a mean half-duration (duration
      at half-maximal amplitude) of 25 +/- 2.3 min, indicating that 95% of daily GH
      secretion occurred in 8.8 h. The majority (96%) of GH was secreted in volleys
      composed of multiple (4.0 +/- 0.4) discrete secretory bursts. Such volleys of GH
      secretion were separated by 171 +/- 19 min, whereas their constituent individual
      secretory events occurred every 36 +/- 1.7 min (P = 0.0001). Between secretory
      volleys, calculated GH secretory rates fell asymptotically to zero. Significant
      positive and negative autocorrelations were observed for the series consisting of
      successive GH secretory burst mass and interburst intervals, respectively. Linear
      regression analysis revealed significant negative correlations between the mass
      of GH secreted per burst and both the preceding and following interburst
      intervals. Estimates of the half-life of endogenous GH (17 +/- 1.7 min) and of
      the endogenous GH production rate (0.25 +/- 0.033 mg/m2 for an assumed
      distribution volume of 7.9% body wt) agreed well with earlier independent
      measurements. We conclude that the human pituitary gland secretes GH in volleys
      consisting of multiple secretory bursts, without measurable intervening tonic
      secretion. This pattern of in vivo GH release in normal humans is consistent with
      a model of high-frequency GH-releasing hormone secretory events superimposed on
      low-frequency episodes of somatostatin withdrawal.

PMID- 1987785
TI  - Leucine kinetics from [2H3]- and [13C]leucine infused simultaneously by gut and
      vein.
AB  - In amino acid tracer kinetic studies of the fed state, ingested amino acid may be
      taken up during its initial transit through splanchnic tissues and thus not enter
      the plasma compartment where tracer is infused. To investigate this possibility,
      adult human subjects received simultaneous intravenous (iv) and intragastric (ig)
      leucine tracer infusions, first during a postabsorptive (PA) 4-h primed
      continuous ig infusion of L-[1-13C]-leucine and L-[5,5,5-2H3]leucine iv, followed
      on a separate day by a fed infusion, in which an ig infusion of a liquid formula
      was started 2 h before the tracer infusion and continued throughout the tracer
      study. Subjects were accustomed to a constant experimental diet supplying 1.5 g
      protein.kg-1.day-1 and 41-45 kcal.kg-1.day-1 for 7 and 12 days before the PA and
      fed studies, respectively. For the PA study, plasma enrichment for the ig tracer
      was 3.34 +/- 0.27 (SE) mol + excess and for the iv tracer it was 4.18 +/- 0.10 (P
      less than 0.02). Enrichments of alpha-keto-isocaproic acid (KIC) were 3.24 +/-
      0.16 (ig) and 3.02 +/- 0.14 (iv), respectively [not significant (NS)]. For the
      fed study, plasma leucine enrichment for the ig tracer was 2.15 +/- 0.14 and for
      the iv tracer was 2.84 +/- 0.09 (P less than 0.02). KIC enrichments were 2.02 +/-
      0.08 (ig) and 2.24 +/- 0.08 (iv), respectively (NS). In the PA study, the ratio
      of the plasma leucine enrichments for the ig and iv tracers was 0.80 +/- 0.06 and
      in the fed experiment, 0.76 +/- 0.05, respectively.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1987786
TI  - Effect of surgical injury and intraoperative hypothermia on whole body protein
      metabolism.
AB  - Whole body protein turnover and urinary nitrogen and 3-methyl-L-histidine (3-MH)
      excretion were measured before and after cardiac surgery using cardiopulmonary
      bypass in 20 male patients randomized to an intraoperative blood temperature of
      28 or 20 degrees C. Rates of whole body protein synthesis (WBPS) and breakdown
      (WBPB) were determined from the 15N isotopic enrichment of urinary urea,
      ammonium, and from a calculated end-product average (EPA) after a primed 24-h
      infusion of [15N]glycine. In the postoperative period, there was a 40% increase
      in median nitrogen excretion in the 28 degrees C group (P less than 0.03) and a
      22% increase in the 20 degrees C group (P = 0.10). There was a 79% increase in
      the median postoperative 3-MH excretion in the 28 degrees C group (P = 0.01) and
      a 66% increase in the median postoperative 3-MH excretion in the 20 degrees C
      group (P less than 0.01). Postoperatively, there was a 23% fall in the median
      value of WBPS in the 28 degrees C group (P less than 0.01) and an 11% fall in the
      20 degrees C group [not significant (NS)] measured by 15N enrichment of urinary
      urea. In contrast, when WBPS was measured from isotopic enrichment of urinary
      ammonium, there was an increase in the median value of the postoperative rates of
      WBPS in both groups, by 20% in the 28 degrees C group (P = NS) and 29% in the 20
      degrees C group (P = 0.03). There was no significant change in the rate of WBPS
      and WBPB, judged by the postoperative EPA in either group.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1987787
TI  - Effect of training on response to a glucose load adjusted for daily carbohydrate
      intake.
AB  - From responses to identical absolute glucose loads in trained (T) and untrained
      (UT) subjects, it has been inferred that training promotes health by reducing
      glucose levels and insulin secretion. To mimic daily living conditions, we
      studied responses to oral glucose loads making up identical fractions of daily
      carbohydrate intake (i.e., same relative glucose load) in seven T and eight UT
      males [maximal O2 uptake (VO2max) 76 +/- 2 vs. 48 +/- 1 (SE) ml.min-1.kg-1; age
      24 +/- 1 vs. 25 +/- 1 yr]. Daily energy intake was higher in T than in UT
      subjects (18,607 +/- 835 vs. 12,493 +/- 720 kJ/day, P less than 0.05), reflecting
      a 2.3 times higher carbohydrate intake (678 +/- 34 vs. 294 +/- 18 g/day, P less
      than 0.05). After 1 g/kg body wt glucose, C-peptide and insulin responses were
      lower in T than in UT subjects (P less than 0.05). However, after identical
      relative glucose loads [high: 2.3 +/- 0.2 (T) vs. 1 (UT) g/kg; low: 1 (T) vs. 0.4
      +/- 0.03 (UT) g/kg], glucose [incremental areas 300 +/- 56 (T) vs. 304 +/- 35
      (UT) mM.180 min and 148 +/- 30 (T) vs. 124 +/- 22 (UT)] and C-peptide [181 +/- 18
      (T) vs. 171 +/- 27 (UT) nM.180 min, and 100 +/- 13 (T) vs. 71 +/- 12 (UT)]
      responses did not differ between groups, while insulin responses were lower in T
      [at low relative load 15 +/- 4 (T) vs. 20 +/- 2 (UT) nM.180 min, P less than
      0.05].(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1987788
TI  - Distinct but nonadditive effects of epinephrine and cortisol on determinants of
      glucose tolerance in dogs.
AB  - Effects of physiological increments of epinephrine (Epi) and cortisol (F) on
      glucose metabolism were assessed in dogs just before and during an intravenous
      glucose tolerance test performed in the last 3 h of an acute (short F + Epi, 4 h
      F and 3.5 h Epi) or prolonged (long F + Epi, 75 h F and Epi) infusion period.
      Comparison of the F + Epi effects with those of F and Epi alone enabled us to
      describe interactions between these hormones. The increase in plasma glucose
      after long F + Epi [from control (saline, Sal) of 5.2 +/- 0.1 to 5.8 +/- 0.1
      mmol/l; n = 8; P less than 0.01] was not greater than the sum of the glucose
      increments after long F and long Epi individually. Long Epi and long F both
      reduced glucose tolerance (KGlc) significantly, but the decline during long F +
      Epi (from Sal 3.6 +/- 0.7 to 2.9 +/- 0.5%/min; P greater than 0.1) was less than
      during either individual infusion. Minimal model analysis showed that F
      attenuated the inhibitory effects of long Epi on glucose-mediated glucose
      disposal (SGlc), so that it was not reduced from 3.8 +/- 0.8 (Sal) during long F
      + Epi compared with the fall to 1.3 +/- 0.7 x 10(-2) min-1 (n = 6; P less than
      0.05) during long Epi alone. F had the dominant influence on insulin sensitivity
      (SI) during infusion of F + Epi. The reduction of SI from 8.4 +/- 1.1 (Sal) to
      6.6 +/- 1.2 (short F + Epi) and 5.1 +/- 1.1 x 10(-4) min-1 per mU/l (long F +
      Epi; P less than 0.05) paralleled that seen with F alone but contrasted with the
      acute reduction of SI during short Epi (4.8 +/- 1.5; P less than 0.02 vs. Sal)
      and its restoration to control values of 9.0 +/- 2.1 x 10(-4) min-1 per mU/l
      during long Epi. We conclude that Epi and F have distinct but nonadditive effects
      on determinants of glucose tolerance.

PMID- 1987789
TI  - Indirect calorimetry: comment.

PMID- 1987790
TI  - Effects of intravenous infusion of 17 amino acids on the secretion of GH,
      glucagon, and insulin in sheep.
AB  - The effects of intravenous infusion of 17 amino acids, each at a dose of 3
      mmol/kg over 30 min, on the secretion of insulin, glucagon, and growth hormone
      (GH) were studied in 6 castrated male sheep. Insulin-like growth factor I (IGF-I)
      secretion was also studied using eight of the amino acids. Plasma alpha-amino
      nitrogen reached a peak at 30 min followed by a gradual decrease thereafter. The
      greatest increase was obtained using aspartic acid and the smallest with
      methionine, responses to the remaining amino acids lying between these two.
      Leucine was the most effective amino acid in stimulating insulin secretion but
      did not produce any increase in glucagon and GH secretion. Alanine, glycine, and
      serine induced a greater enhancement of both glucagon and insulin secretion than
      other amino acids. No amino acid was able to specifically stimulate glucagon
      secretion without also increasing insulin or GH secretion. With regard to insulin
      and glucagon secretion, amino acids could be divided into groups according to
      their R groups. Neutral straight-chain amino acids stimulated both insulin and
      glucagon secretion, with a greater secretory response to shorter C-chain amino
      acids. Branched-chain amino acids tended to enhance insulin and suppress glucagon
      secretion. Acidic amino acids caused an increase in GH secretion. Aspartic acid
      caused the strongest stimulation of GH secretion, exceeding that induced by
      arginine. No changes in plasma IGF-I were brought about by any of the amino acids
      tested.

PMID- 1987791
TI  - Body composition and metabolic rate in rat during a continuous infusion of
      cachectin.
AB  - Changes in brain metabolites, energy balance, resting metabolic rate, body
      composition, and organ histology were studied over 10 days in control (C),
      cachectin-infused (CIR), and pair-fed (PFR) (in relation to CIR) rats. The
      cachectin was continuously infused for the 10 days into the superior vena cava at
      the rate of approximately 100 micrograms.kg-1.day-1. The brain of the CIR had
      significantly more tryptophan and 5-hydroxyindole-3-acetic acid than C and PFR.
      The CIR rats were anorexic, hypermetabolic, relatively hyperglycemic, and had
      raised blood urea nitrogen with comparable creatinine levels when compared with
      similarly wasted PFR. They had significant loss of muscle mass, especially in
      muscles with a predominance of type II fibers. However they gained liver, heart,
      and lung mass. The loss of muscle mass could be ascribed to dietary deficiency,
      but the gain in visceral mass was associated with an increase in organ DNA and
      protein. Histology showed that there was cell proliferation in the liver, heart,
      and kidneys. The data are consistent with centrally mediated anorexia with
      nutritionally mediated muscle wasting but with visceral hypermetabolism, protein
      accumulation, and cell proliferation.

PMID- 1987792
TI  - Interaction of exercise and insulin action in humans.
AB  - To assess the interaction of exercise and insulin action, healthy males were
      studied with saline infusion (n = 5) or with a hyperinsulinemic euglycemic clamp
      (0.5, 1.0, 2.0, or 15.0 mU.kg-1.min-1; n = 5 at each dose) during rest (40 min),
      moderate-intensity cycle exercise (100 min), and recovery (100 min). Metabolism
      was assessed using isotopic methods and indirect calorimetry. During rest,
      exercise, and recovery with saline infusion, plasma glucose was unchanged, total
      glucose utilization (Rd) was 2.4 +/- 0.4, 4.9 +/- 0.2, and 2.6 +/- 0.2 mg.kg
      1.min-1, and carbohydrate (CHO) oxidation (OX) was 1.4 +/- 0.3, 10.6 +/- 1.1, and
      0.5 +/- 0.2 mg.kg-1.min-1. The glucose infusion, insulin-dependent Rd, and CHO OX
      increased synergistically when exercise and insulin clamps were combined.
      Exercise decreased (P less than 0.05) the half-maximal doses (ED50) and increased
      the maximal responses (Vmax) for insulin-dependent Rd and CHO OX. Estimates of
      insulin-independent Rd were 1.3 +/- 0.7, 4.1 +/- 1.3, and 1.9 +/- 0.7 mg.kg-1.min
      1 and insulin-independent CHO OX were 1.2 +/- 0.9, 10.4 +/- 1.3, and 0.6 +/- 0.3
      mg.kg-1.min-1 during rest, exercise, and recovery. Estimates during exercise were
      greater than those at rest (P less than 0.05). The total suppression of free
      fatty acids (FFA) and fat OX by insulin were elevated by exercise (P less than
      0.05). In summary, exercise and insulin interact synergistically in stimulating
      Rd and CHO OX.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1987793
TI  - Effect of systemic hyperinsulinemia on amino acid flux across human legs in
      postabsorptive state.
AB  - The effect of physiological hyperinsulinemia (approximately 110 mU/l) on leg
      tissue protein balance was investigated in eight weight-stable healthy
      individuals. A primed constant infusion of L-[U-14C]tyrosine was used to measure
      the disposal and release of tyrosine across the leg before and during 2 h of
      euglycemic clamp studies. The leg exchange of 3-methyl-L-histidine (3-MH) and all
      amino acids in blood were measured before and during insulinization, including
      the muscle tissue content of amino acids. Hyperinsulinemia decreased whole body
      tyrosine flux from 52 +/- 2 to 35 +/- 1 mumol/min (P less than 0.0001), whereas
      neither disposal (53 +/- 9 vs. 45 +/- 9 nmol.min-1.100 g-1) nor release of
      tyrosine across the leg (76 +/- 11 vs. 66 +/- 10 nmol X min-1 X 100 g-1) was
      significantly influenced. The arterial concentration and the leg exchange of 3-MH
      were not significantly affected by 2 h of hyperinsulinemia, but the sum of all
      amino acids declined significantly. The net leg balance of tyrosine was not
      affected at all by hyperinsulinemia, whereas the balance of the branched-chain
      amino acids and methionine were switched from efflux toward influx. Phenylalanine
      efflux from the leg only showed a trend to a significant effect by insulin. The
      muscle tissue concentration of six individual amino acids decreased significantly
      during hyperinsulinemia, particularly the branched-chain amino acids. The leg
      exchange of glucose, free fatty acids, and glycerol immediately changed
      significantly, as expected in response to insulinization.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1987794
TI  - Hierarchy of glycemic thresholds for counterregulatory hormone secretion,
      symptoms, and cerebral dysfunction.
AB  - To define glycemic thresholds for activation of counterregulatory hormone
      secretion, initiation of symptoms (autonomic and neuroglycopenic), and onset of
      deterioration of cognitive function, we measured indexes of these responses
      during glycemic plateaus of 90, 78, 66, 54, and 42 mg/dl in 10 normal volunteers,
      with the use of the hyperinsulinemic glucose clamp technique. Activation of
      glucagon, epinephrine, norepinephrine, and growth hormone secretion began at
      arterialized venous plasma glucose concentrations of 68 +/- 1, 68 +/- 1, 65 +/-
      1, and 67 +/- 2 (SE) mg/dl, respectively. Autonomic symptoms (anxiety,
      palpitations, sweating, irritability, and tremor) began at 58 +/- 2 mg/dl, which
      was significantly (P = 0.0001) lower. Neuroglycopenic symptoms (hunger,
      dizziness, tingling, blurred vision, difficulty thinking, and faintness) and
      deterioration in cognitive function tests began at 51 +/- 3 and 49 +/- 2 mg/dl,
      respectively, values that were both significantly (P = 0.018 and 0.004,
      respectively) lower than that for initiation of autonomic symptoms. We therefore
      conclude that there is a distinct hierarchy of responses to decrements in plasma
      glucose, such that the threshold for activation of counterregulatory hormone
      secretion occurs at higher plasma glucose levels than that for initiation of
      autonomic warning symptoms, which in turn occurs at higher plasma glucose levels
      than that for onset of neuroglycopenic symptoms and deterioration in cerebral
      function. Such a hierarchy would maximize the opportunity to avoid incapacitating
      hypoglycemia.

PMID- 1987796
TI  - Muscle mitochondrial morphology, body composition, and energy expenditure in
      sedentary individuals.
AB  - To investigate whether differences in metabolic rate are related to differences
      in muscle mitochondrial morphology and/or to differences in in vitro muscle
      respiration, we studied 17 healthy Caucasians, covering a wide range of body
      weight and composition [9 males, 8 females; body wt 96 +/- 37 (SD) kg; body fat =
      28 +/- 10%]. Central and peripheral mitochondrial volume density (Vmit c and Vmit
      p, respectively) and the ratio of mitochondrial outer surface to volume of
      mitochondria (SVmit c in center and SVmit p at periphery) were determined by
      stereological analyses of transmission electron micrographs from samples of the
      vastus lateralis. There was no relationship between mitochondrial morphology or
      muscle respiration and 24-h energy expenditure, basal metabolic rate, or sleeping
      energy expenditure adjusted for differences in fat-free mass, fat mass, age, and
      sex. Although total body fat was not associated with muscle cell morphology,
      central distribution of body fat [waist-to-thigh circumference ratio (W/T)]
      correlated negatively with Vmit c (r = -0.58, P = 0.01), SVmit c (r = -0.59, P =
      0.01), and SVmit p (r = -0.48, P = 0.05). W/T was also negatively related to
      muscle respiration (r = -0.59, P = 0.01). Despite the lack of relationship
      between metabolic rate and muscle mitochondrial morphology, central distribution
      of body fat is associated with lower mitochondrial density and larger
      mitochondria in skeletal muscle and is associated with a decreased oxidative
      capacity of muscle.

PMID- 1987795
TI  - Angiotensin II and alpha-agonist. III. In vitro fetal-maternal placental
      prostaglandins.
AB  - In fetal sheep, angiotensin II, but not phenylephrine, increases umbilical venous
      concentrations of prostaglandin E2 (PGE2) and prostacyclin (PGI2); however, their
      source(s) is unknown. We sought to determine the tissue source(s) of this
      increase in prostanoids and to compare responses in fetal and maternal tissues.
      Fetal placental arteries (PA) and veins (PV), mesenteric arteries (MA) and
      cotyledons, and maternal caruncles and uterine arteries (UA) from eight pregnant
      ewes [127 +/- 3 (SE) days] were incubated (37 degrees C, 1 h) in Krebs-Henseleit
      (95% O2-5% CO2) with or without angiotensin II, phenylephrine, or norepinephrine
      (5 x 10(-10) and 5 x 10(-8) M). Basal PGE2 production exceeded PGI2 in PA,
      cotyledons, and caruncles (P less than 0.05), whereas PGE2 less than PGI2 only in
      UA; production of both prostanoids was greatest in MA with 34.8 +/- 5.0 and 27.4
      +/- 3.7 pg.micrograms protein-1.h-1, respectively (P less than 0.001). Caruncles
      produced little of either prostanoid. Angiotensin II increased PA PGE2 production
      from 6.5 +/- 1.5 to 8.4 +/- 3.0 and 10.8 +/- 4.5 pg.micrograms-1.h-1 (P = 0.001)
      and PGI2 from 3.3 +/- 0.5 to 5.5 +/- 1.5 (P less than 0.05) and 3.7 +/- 0.9
      pg.micrograms-1.h-1; PV PGE2 rose from 4.5 +/- 1.1 to 9.0 +/- 3.5 and 7.9 +/- 2.3
      pg.micrograms-1.h-1 (P less than 0.05); PV PGI2 was unchanged. Angiotensin II
      increased UA PGE2 from 1.5 +/- 0.3 to 3.4 +/- 1.2 (P less than 0.05) and 2.4 +/-
      0.8 pg.micrograms-1.h-1 and PGI2 from 8.7 +/- 1.0 to 12.4 +/- 2.2 and 16.2 +/-
      5.2 (P less than 0.05) pg.micrograms-1.h-1. Angiotensin II had no effect on MA,
      cotyledonary, or caruncular prostanoids. alpha-Agonist had no effect on any
      tissue examined. In fetal sheep, angiotensin II-induced increases in PGI2 and
      PGE2 are likely of vascular origin.

PMID- 1987797
TI  - Hypertension and sympathetic hyperactivity induced in rats by high-fat or glucose
      diets.
AB  - Male Sprague-Dawley rats fed either a high-fat diet or a glucose-enriched diet
      developed higher blood pressure (BP) than rats fed a control diet. After 8 wk of
      diet treatment systolic BP was 11% higher (P less than 0.01) in fat-fed rats and
      7% higher (P less than 0.05) in glucose-fed rats when compared with rats fed the
      control diet. Rats fed the high-fat diet developed hypertension only when they
      were allowed to overeat and become obese and hyperinsulinemic. But when their
      feeding was restricted to prevent obesity and hyperinsulinemia, they remained
      normotensive. In contrast, elevated BP developed in rats consuming the glucose
      diet in the absence of obesity or hyperinsulinemia. After 7 wk of diet treatment,
      urinary norepinephrine excretion was 1.9 +/- 0.1, 1.9 +/- 0.1, and 1.5 +/- 0.1
      micrograms/day in rats fed the high-fat, glucose, and control diets, respectively
      (P less than 0.05 vs. control). Higher norepinephrine excretion in hypertensive
      rats suggests that increased sympathetic nervous system (SNS) activity might
      participate in mediating the effects of dietary fat or glucose on BP. In
      addition, insulin may contribute to raising BP in rats fed the high-fat diet,
      either directly or indirectly through its stimulatory effect on the SNS. We
      conclude that chronic feeding of diets high in fat or glucose increases BP and
      enhances SNS activity in rats.

PMID- 1987798
TI  - Influence of anesthesia, postanesthetic state, and restraint on superior
      mesenteric arterial flow in normal rats.
AB  - To exclude possible confounding effects of anesthesia on splanchnic hemodynamics,
      two different awake postanesthetic models (PAM), restrained and unrestrained,
      have been used. However critical analysis of the splanchnic hemodynamic state in
      these models is not available. We conducted experiments using chronically
      implanted pulsed-Doppler flow probes on the superior mesenteric artery (SMA) in
      ketamine-anesthetized and in postanesthetic restrained and unrestrained normal
      rats. Baseline values of mean SMA flow were compared with those under anesthesia
      (30 min), PAM (restrained or unrestrained at 90 and 150 min), and reanesthesia.
      Sham-anesthetized unrestrained animals provided control values. The same animals
      (n = 7) underwent the restrained, unrestrained, and control experiments at least
      5 days apart. Ketamine anesthesia did not significantly alter mean SMA flow (89
      +/- 9% of baseline) compared with sham-anesthetized controls (99 +/- 9%). Mean
      SMA flow in both PAM, restrained and unrestrained, had a significant (P less than
      0.05) decrease at 90 min (78 +/- 8 and 83 +/- 12%) and at 150 min (68 +/- 14 and
      78 +/- 14%) when compared with baseline and control. Reanesthesia returned SMA
      flows to baseline values (91 +/- 16%). The variability of mean SMA flow was
      significantly increased in both PAM. Maximum variability was observed in the
      restrained model (69 +/- 32%). These results indicate 1) that ketamine anesthesia
      does not significantly alter SMA flow and 2) that both the restrained and
      unrestrained PAM exhibit significant alterations of the splanchnic circulation
      for at least 2 h after complete recovery from anesthesia. Thus, in the absence of
      critical evaluation, results of splanchnic hemodynamic studies with these models
      should be questioned.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1987799
TI  - Dietary regulation of intestinal ascorbate uptake in guinea pigs.
AB  - We measured ascorbic acid (AA) uptake across the intestinal brush border in vitro
      in intact tissue from guinea pigs fed maintenance AA (200 mg/kg diet) or made
      hypervitaminotic (5,000 mg/kg diet) or hypovitaminotic (chronically and acutely).
      Total uptake per centimeter ileum was 25-50% lower in hypervitaminotic juvenile,
      adult male, and lactating guinea pigs compared with their respective controls,
      whereas carrier-mediated D-glucose uptake and Na(+)-independent AA uptake were
      similar. High dietary ascorbate specifically reduced the Vmax for carrier
      mediated AA uptake. Hypovitaminosis had no significant effect on uptake of AA or
      other solutes. We performed diet-switching experiments (high-AA diet to
      maintenance diet) with young and adult guinea pigs to determine the reversibility
      of the downregulation. In adult guinea pigs, the downregulation of AA uptake was
      reversible within 7 days. In the young of mothers fed high AA during pregnancy
      and lactation, and which fed on high AA for 14 days after weaning, the
      downregulation was reversible within 14 days. Thus regulation of AA uptake is
      reversible and therefore probably does not play a significant role in the
      development of vitamin C dependency in human adults, or their young, after
      ingestion of megadoses of ascorbic acid.

PMID- 1987800
TI  - Taurocholate induces pericanalicular localization of C6-NBD-ceramide in isolated
      hepatocyte couplets.
AB  - The mechanisms and pathways involved in hepatocellular transport of lipid
      destined for biliary excretion remain poorly understood. Using fluorescence
      microscopy of rat hepatocyte couplets in primary culture, we examined the effects
      of taurocholate (TC) on the intracellular distribution of 6-N-[7-nitrobenz-2-oxa
      1,3-diazol- 4-yl]aminocaproyl-sphingosine (C6-NBD-ceramide), a lipid that
      accumulates in the Golgi apparatus. Microscopic findings were quantified with
      morphometric and digital image analysis and were correlated with the metabolism
      of C6-NBD-ceramide in isolated hepatocyte suspensions and the biliary excretion
      of fluorescent lipid in the isolated perfused liver. After plasma membrane uptake
      of C6-NBD-ceramide from albumin at 0 degrees C, the lipid was rapidly
      internalized at 37 degrees C but exhibited only a modest concentration of
      fluorescence in intracellular organelles. With 17 microM TC in the medium, there
      was enhanced localization of fluorescence to organelles and significant
      recruitment of fluorescent lipid to the pericanalicular region of the couples
      within 30 min. C6-NBD-ceramide was partially metabolized to C6-NBD-sphingomyelin
      and -glucosylceramide, indicative of transit through the Golgi apparatus. The
      generation of C6-NBD-sphingomyelin was significantly increased by TC. After a
      similar loading protocol in the perfused liver, there was little biliary
      excretion of fluorescent lipid at 37 degrees C under control conditions. However,
      infusion of TC markedly enhanced the biliary output of fluorescent lipid over the
      first 30 min, primarily as C6-NBD-sphingomyelin and -glucosylceramide. We
      conclude that TC modulates the distribution of C6-NBD-ceramide in hepatocytes by
      inducing translocation of lipid to a pericanalicular location, most likely the
      Golgi apparatus, before excretion of its metabolites in bile. Our findings
      support the concept that bile salt-induced biliary lipid excretion is facilitated
      by the interaction of bile salts with lipids at the level of intracellular
      organelles.

PMID- 1987801
TI  - Unprepared human colon does not discriminate between solids and liquids.
AB  - In five healthy male volunteers, we compared solid and liquid transit though the
      unprepared colon. 99mTc-diethylenetriaminepentaacetic acid in 10 ml saline was
      injected into the cecum through an orocecal tube at 1 ml/min immediately after a
      methacrylate-coated medication capsule was seen to deliver 111In-labeled
      Amberlite IR-120PLUS pellets (avg diam, 1.0 mm) into the cecum. Segmental
      transits through the ascending, transverse, descending, and rectosigmoid regions
      were determined using a dual gamma camera system and a variable region of
      interest program. There was no difference between solid [half time, 247 +/- 60
      (SE) min] and liquid (312 +/- 88 min) emptying from the ascending colon. Colonic
      transit of solids and liquids was further compared by regional counts and stool
      outputs at 12 and 24 h. There were no significant differences between solids and
      liquids (P greater than 0.05). Our data suggest that transit through the
      unprepared human colon is not different for solids and small volumes of liquids,
      when these are delivered together to the ascending colon.

PMID- 1987802
TI  - Differential effects of calcium ions and calcium phosphate on cytotoxicity of
      bile acids.
AB  - Unconjugated secondary bile acids can promote colon cancer by damaging colonic
      mucosa and consequently increasing epithelial proliferation. It has been proposed
      that dietary calcium inactivates intestinal bile acids either by a Ca2(+)
      dependent precipitation or by binding to insoluble calcium phosphate (CaPi). We
      studied the molecular mechanisms of these opposing hypotheses by using hemolysis
      of erythrocytes as a model parameter for cytotoxicity. Washed human erythrocytes
      were incubated for 15 min with buffered media (pH 7.4) containing increasing
      amounts of different bile acids. Deconjugation and 7 alpha-dehydroxylation of
      mixtures of glycine- or taurine-conjugated cholate and chenodeoxycholate
      drastically increased their cytotoxicity. Parallel measurements, using a
      fluorescent micellar probe, indicated that micellar aggregation is a prerequisite
      for this bile acid-induced lysis. Ca2+ concentrations up to 15 mM did not
      precipitate bile acids but stimulated cytotoxicity of both deoxycholate (DC) and
      its glycine conjugate (GDC). Cytotoxicity of the taurine conjugate (TDC) was
      stimulated to a much lesser extent. Increasing amounts of CaPi precipitated
      micellar DC and GDC, but not TDC, and consequently inhibited only cytotoxicity of
      the former two. These findings indicate that 1) hydrophobicity and micellar
      aggregation are important determinants of bile acid-induced cytotoxicity that
      explain the high cytotoxic potential of secondary bile acids in colon, and 2)
      cytotoxicity of bile acids is stimulated by free Ca2+ and inhibited by CaPi. This
      inhibition is due to binding of carboxylic (including secondary) bile acids to
      CaPi.

PMID- 1987803
TI  - Neuromuscular mechanisms of esophageal responses at and proximal to a distending
      balloon.
AB  - To determine the neuromuscular mechanisms involved in esophageal responses at and
      proximal to a distending stimulus, a manometric catheter incorporating a latex
      balloon at its distal end was positioned in the smooth muscle esophagus of alpha
      chloralose-anesthetized opossums and used to record intraluminal pressures over
      the balloon and at several sites proximal to the balloon. Air inflation of the
      balloon evoked simultaneous phasic contractions at several sites proximal to the
      balloon that were abolished by bilateral cervical vagotomy. With the balloon
      located in the midesophagus, these proximal contractions were also abolished by
      atropine, and simultaneous suction electrode recordings indicated that they were
      associated with smooth muscle membrane depolarization and spike burst without
      preceding hyperpolarization. With the balloon located in the distal esophagus,
      the evoked proximal contractions were less atropine sensitive. Phasic pressure
      fluctuations recorded by the balloon itself were not affected by atropine or
      bilateral cervical vagotomy but were increased in amplitude by tetrodotoxin.
      These opossum studies suggest that unlike responses below a distending balloon,
      which have been shown to be noncholinergic and mediated by intramural
      neuromuscular mechanisms, proximal contractions depend on vagal pathways and,
      depending on esophageal location, muscarinic-cholinergic transmission.
      Contractions at the level of the distending balloon appear to be myogenic in
      origin.

PMID- 1987804
TI  - Regulation of acid secretion by bombesin/GRP neurons of the gastric fundus.
AB  - Intramural neurons in the fundus of the isolated mouse stomach were activated by
      1,1-dimethyl-4-phenylpiperazinium (DMPP) or by electrical field stimulation and
      the participation of cholinergic and bombesin/gastrin-releasing peptide (GRP)
      neurons in the regulation of acid secretion evaluated with atropine and a
      selective bombesin/GRP antagonist, [Leu13-psi(CH2NH)-Leu14]bombesin. For both
      DMPP and field stimulation, atropine inhibited acid secretion and augmented
      somatostatin secretion. The bombesin/GRP antagonist had an opposite effect,
      augmenting acid secretion and inhibiting somatostatin secretion to below basal
      levels. The combination of the two antagonists restored DMPP- and field
      stimulated acid and somatostatin secretion to basal levels. The results indicate
      that neurally stimulated acid secretion in the isolated mouse stomach is
      regulated by cholinergic neurons that mediate stimulation and bombesin/GRP
      neurons that mediate inhibition of acid secretion. Cholinergic neurons exert
      their stimulatory effect by acting directly on parietal cells and indirectly by
      eliminating the inhibitory influence of somatostatin. Bombesin/GRP neurons exert
      their inhibitory effect mainly by inducing release of somatostatin; an additional
      direct inhibitory effect of bombesin/GRP neurons on parietal cells is possible.

PMID- 1987805
TI  - Hemodynamic characterization of conscious and ketamine-anesthetized bile duct
      ligated rats.
AB  - The present study was conducted to characterize the hemodynamic alterations in
      common bile duct-ligated (CBDL) rats under ketamine anesthesia and in the awake
      restrained state. Hemodynamic studies using the radioactive microspheres
      technique were performed 17.6 +/- 0.6 (SE) days after bile duct ligation or sham
      operation. CBDL rats had lower mean arterial pressure, reduced systemic and renal
      resistance, and increased renal blood flow compared with sham-operated rats. This
      was found both in the conscious and anesthetized states. Anesthetized CBDL rats
      had higher portal pressure (13.2 +/- 0.5 vs. 9.2 +/- 0.4 mmHg; P less than 0.001)
      and lower splanchnic arteriolar resistance (15.4 +/- 1.3 vs 26.8 +/- 4.6 mmHg.ml
      1.min.100 g body wt; P less than 0.05) than sham-operated rats. Portosystemic
      shunting was 52.3 +/- 11.7% in CBDL and negligible in sham-operated rats. The
      last three parameters could not be measured in conscious animals. Total
      peripheral resistance was lower in the conscious than in the anesthetized state,
      diverting a higher fraction of cardiac output at the expense of splanchnic organs
      and leading to a significant reduction of portal venous inflow in sham-operated
      but not in CBDL rats [3.36 +/- 0.47 vs. 5.38 +/- 0.65 (P less than 0.05) and 5.33
      +/- 0.58 vs. 6.34 +/- 0.37 ml.min-1.100 g body wt-1 (P = NS), respectively].
      These findings indicate that CBDL and normal rats respond differently to
      anesthesia and restraint. Because the restrained state is stressful and studies
      in anesthetized animals are technically simpler, provide additional information
      such as portal pressure and portosystemic shunting, and diminish animal
      suffering, we suggest that hemodynamic studies in rats, using the microsphere
      technique, should be preferably performed under ketamine anesthesia.

PMID- 1987806
TI  - Variations in muscle tone of the human rectum: recordings with an
      electromechanical barostat.
AB  - Rectal wall tone (the contractile state of the rectal tunica muscularis) should
      mediate accommodation and influence rectal emptying. Such changes in tone however
      can be only inferred from changes in baseline pressure recorded with conventional
      manometry. We used an isobaric volumetric device, the rectal electromechanical
      barostat, to quantify variations in tone of the rectal wall in response to
      feeding and to perturbations in response to the pharmacological agents
      neostigmine and glucagon. The barostat quantitates muscular wall tone indirectly
      by measuring its reciprocal, e.g., the volume of air within a flaccid
      intraluminal bag that is maintained at a constant and preselected pressure, by an
      electronic feedback mechanism. The barostat as well as a three-channel perfused
      manometric catheter were positioned in the rectum of 14 healthy volunteers. Three
      patterns of changes were observed: 1) respiratory fluctuations, 2) rapid volume
      waves, and 3) slow volume changes. Rectal tone varied little during fasting;
      rapid or slow changes in intrabag volume were infrequent. Ingestion of a standard
      meal was followed by a significant decrease in barostat bag volume (85 +/- 6 ml
      fasting vs. 50 +/- 8 ml fed, P less than 0.05). Pharmacological agents also
      induced predictable responses; neostigmine decreased bag volume and induced
      phasic pressure activity, whereas glucagon abolished phasic pressure activity and
      increased barostat bag volume. Perfused manometric catheters showed no
      concomitant changes in baseline pressure. We concluded that a rectal barostat
      measured variations in human rectal tone, which were not recorded by conventional
      manometric techniques. These changes in rectal tone might have important
      functional significance.

PMID- 1987807
TI  - Comparison of primary and secondary esophageal peristalsis in humans: effect of
      atropine.
AB  - To determine whether physiological differences exist between primary (swallow
      induced) and secondary (distension-induced) peristalsis in humans, 10 healthy
      male volunteers underwent esophageal manometry on 2 consecutive days using a
      perfused intraluminal catheter system that incorporated a latex balloon.
      Initially the catheter was positioned so that the balloon was centered 16 cm
      above the lower esophageal sphincter (LES), and intraluminal pressures were
      recorded 21, 11, 6, and 1 cm above the LES. After a series of wet swallows, dry
      swallows, and balloon distensions, the catheter was repositioned so that the
      balloon was 6 cm above the LES and pressures were recorded 1 and 11 cm above the
      LES. A series of balloon distensions were repeated in this position, and the
      subject was then given either atropine (10 micrograms/kg iv) or placebo in a
      double-blind randomized fashion (on consecutive days). The protocol was then
      repeated in reverse order. Distension-induced responses aboral to the balloon
      with the balloon located 16 cm above the LES were 1) of lower amplitude, 2) more
      often nonperistaltic, and 3) less atropine sensitive than swallow-induced
      contractions at comparable sites. With the balloon located distally (6 cm above
      LES) contractions induced at the 11-cm site (i.e., orad to the balloon) were much
      more atropine sensitive than contractions induced at the same site when the
      balloon was located proximally (i.e., 16 cm above LES). These data suggest that,
      contrary to previous reports, secondary peristalsis differs significantly from
      primary peristalsis. Furthermore, atropine differentially effects these two types
      of peristalsis, suggesting that the neural pathways involved are dissimilar.

PMID- 1987808
TI  - Effect of UDCA on intracellular and biliary pH in isolated rat hepatocyte
      couplets and perfused livers.
AB  - To study how ursodeoxycholic acid (UDCA) increases biliary HCO3- concentration
      and alkalinizes bile, intracellular pH (pHi) and canalicular pH (pHc) were
      measured microfluorimetrically in isolated rat hepatocyte couplets (IRHC).
      Isolated perfused rat livers (IPRL) were also used to assess the roles of Cl-,
      HCO3-, and zone III hepatocytes. In IRHC, UDCA diminished pHi only when HCO3- was
      omitted. pHi recovery was inhibited by amiloride. UDCA did not affect pHi
      recovery from an acid load (NH4Cl) nor modify pHc (+HCO3-). In IPRL, biliary HCO3
      concentration increased following UDCA despite removal of Cl- (to inhibit Cl(-)
      HCO3- exchanger) or destruction of zone III hepatocytes with digitonin. Moreover,
      when HCO3- was omitted from the perfusate, biliary pH rose following UDCA even
      though the hypercholeresis was abolished. Thus 1) hepatic UDCA uptake represents
      an acid load that is counteracted by Na(+)-H+ exchange when HCO3- is absent; 2)
      UDCA does not alkalinize pHc; and 3) alkalinization of biliary pH in IPRL is not
      HCO3- dependent, does not involve Cl(-)-HCO3- exchange, or zonal differences in
      UDCA metabolism or excretion. UDCA appears to alkalinize bile by protonation
      within the bile duct lumen. UDCAH may then cross the biliary epithelium.

PMID- 1987809
TI  - Glucose utilization by Kupffer cells, endothelial cells, and granulocytes in
      endotoxemic rat liver.
AB  - There are several types of glucose-consuming, immunologically active
      nonparenchymal cells interspersed among the glucose-producing parenchymal liver
      cells. Combining the in vivo 2-deoxyglucose tracer technique with cell separation
      methods enabled us to investigate the effect of Escherichia coli endotoxin on the
      rate of glucose utilization by the nonparenchymal cells. Rats were injected with
      [14C]deoxyglucose, and intracellular 2-deoxyglucose 6-phosphate was determined in
      different liver cell fractions. Parenchymal, Kupffer, and endothelial cells as
      well as polymorphonuclear leukocytes (PMN) were separated from the liver by
      centrifugal elutriation followed by Ficoll-Hypaque density gradient. The number
      of PMN obtained from the liver was increased severalfold 3 h after endotoxin and
      was comparable to the number of Kupffer cells. Glucose utilization by the liver
      of fasted rats was due predominantly to nonparenchymal cells. Endotoxin enhanced
      the rate of glucose utilization by Kupffer (6.7-fold) and endothelial (2.7-fold)
      cells and by the infiltrated hepatic PMN (5.4-fold). Enhanced glucose metabolism
      of immunologically active cells is part of the hepatic immune response and
      subserves the antibacterial defense of the body. The activated cells, however,
      may also have the potential of causing tissue damage by releasing harmful toxic
      metabolites.

PMID- 1987810
TI  - Interconversions of lipid aggregates in rat and model bile.
AB  - The dynamic interchange of cholesterol and the phase transition between
      nonmicellar and micellar aggregates in rat and model bile were characterized with
      gel-permeation chromatography, quasi-elastic light scattering, turbidity
      measurements, and by radiolabeling lipid aggregates in bile. Cholesterol
      partitioned into either the micellar or nonmicellar phases independent of the
      lipid aggregate structure. In model bile, increasing bile salt concentrations led
      to a decrease in the relative proportion of nonmicellar aggregates beginning at 5
      mM taurocholate (TC), while the relative cholesterol content of the nonmicellar
      fraction increased from 1.0 to 2.7 +/- 2.0 (means +/- SD). In rats, creation of a
      biliary fistula resulted in a decrease of bile salts from 41 to 4 mM. Mixed
      micelles increased from 25 to 120 A in radius, while nonmicellar aggregates
      increased from 180 to 800 A in radius. Addition of TC to model bile
      (cholesterol:lecithin = 1:1) vesicles with total lipid concentrations less than 7
      mM yielded a progressive shift of vesicles (450 A) to mixed micelles (30 A). For
      mixtures with higher total lipid concentrations, addition of TC promoted
      substantial vesicle aggregation and resulted in formation of a third phase
      containing lipid aggregates larger in size than the initial vesicles. These
      results suggest that rapid exchange of cholesterol occurs in bile and that
      significant remodeling of vesicles can occur. These alterations in vesicles
      include both enrichment in cholesterol content and formation of larger aggregates
      during increases in bile salt concentration.

PMID- 1987811
TI  - Use of stereoisomers of zacopride to analyze actions of 5-hydroxytryptamine on
      enteric neurons.
AB  - Two subtypes of excitatory 5-hydroxytryptamine (5-HT) receptor, 5-HT1P and 5-HT3,
      are found on type 2-AH neurons of the guinea pig myenteric plexus. The 5-HT1P
      receptor mediates a slow and the 5-HT3 receptor a fast depolarization of these
      cells, however, the role of these receptors in the physiology of the gut is
      unknown. Renzapride (BRL 24924), a substituted benzamide, has previously been
      found to antagonize responses of myenteric neurons mediated by both 5-HT1P and 5
      HT3 receptors. The effects on myenteric type 2-AH neurons of a structurally
      similar benzamide, zacopride, which unlike renzapride has S and R stereoisomers,
      were investigated to gain further insight into 5-HT receptor function. In
      contrast to renzapride, S-, but not R-zacopride, was found to mimic the 5-HT1P
      receptor-mediated slow response to 5-HT. Desensitization of 5-HT1P receptors with
      5-HT inhibited slow depolarizing responses to S-zacopride, and desensitization
      with S-zacopride antagonized slow responses to 5-HT. Responses to S-zacopride
      were also inhibited by renzapride and the 5-HT1P receptor antagonist N-acetyl-5
      hydroxytryptophyl-5-hydroxytryptophan amide (5-HTP-DP). S-zacopride, like
      renzapride and 5-HT, presynaptically inhibited nicotinic fast excitatory
      postsynaptic potentials, an effect that can be mediated by 5-HT1P or 5-HT1A
      receptors. Both S and R stereoisomers of zacopride antagonized 5-HT3 receptor
      mediated fast responses to 5-HT. Unlike 5-HTP-DP, neither zacopride or its
      stereoisomers nor renzapride inhibited the binding of 5-[3H]HT to 5-HT1P
      receptors. [3H]zacopride (5-10 nM) was found to bind to a site in the gut from
      which it could be displaced by a 1,000-fold excess of renzapride and S-zacopride
      (but not R-zacopride) greater than 5-HTP-DP much greater than the 5-HT3 receptor
      antagonist ICS 205-930. These observations suggest that, in addition to 5-HT3
      receptors, there is a benzamide binding site on myenteric neurons that interacts
      with, but is distinct from, the 5-HT recognition site of 5-HT1P receptors.
      Benzamides may affect coupling of the 5-HT1P receptor to its effector.

PMID- 1987812
TI  - The APA Task Force report on benzodiazepine dependence, toxicity, and abuse.

PMID- 1987813
TI  - Clarification of projective identification.
AB  - This paper clarifies the various current usages of the term "projective
      identification." The author presents a broad reference model of projective
      identification based on the work of Ogden. This model divides projective
      identification into three steps. Step 1 is the projection of a part of oneself
      onto an external object. Step 1a is the blurring of self and object
      representations. Step 2 is an interpersonal interaction in which the projector
      actively pressures the recipient to think, feel, and act in accordance with the
      projection. Step 3 is the reinternalization of the projection after it has been
      psychologically processed by the recipient. The different definitions of
      projective identification are shown to relate to exactly how the term
      "projection" is conceptualized (in step 1), to whether step 1a is deemed
      necessary, and to how many of the three steps are required for the definition of
      projective identification. The author reviews the work of Ogden, Kernberg,
      Meissner, Sandler, Malin and Grotstein, Porder, and Zinner et al. Six detailed
      case examples are provided from within and outside psychotherapy to illustrate
      all three steps of projective identification.

PMID- 1987814
TI  - Characterization of depression in war-related posttraumatic stress disorder.
AB  - OBJECTIVE: Many patients with posttraumatic stress disorder (PTSD) have symptoms
      of depression, but operationalized psychological constructs related to depression
      have not been used extensively in characterizing affective symptoms of PTSD. The
      authors' objective is to better characterize the affective component of PTSD.
      METHOD: The subjects were 45 male psychiatric inpatients at a Veterans
      Administration medical center; 28 met DSM-III-R criteria for PTSD and 17 met
      Research Diagnostic Criteria (RDC) for major depressive disorder. All of the
      subjects with PTSD were Vietnam veterans. The 21-item Hamilton Rating Scale for
      Depression was used to assess state measures of symptom severity, and the
      Depressive Experiences Questionnaire was used to measure dimensions of
      dependency, self-criticism, and self-efficacy. RESULTS: The mean total Hamilton
      scale score of the patients with PTSD was nonsignificantly higher than that of
      the patients with major depressive disorder; patients with PTSD had higher scores
      on almost all individual Hamilton symptoms, particularly insomnia, somatic
      anxiety, and diurnal variation. Patients with PTSD had significantly higher
      scores on the self-criticism scale but not on the dependency and self-efficacy
      scales of the Depressive Experiences Questionnaire. The scores of patients with
      PTSD on the dependency and self-criticism scales were negatively correlated. No
      significant differences between patients with PTSD with and without concurrent
      major depressive disorder were observed. CONCLUSIONS: Characterization of such
      depressive dimensions of PTSD as dependency and self-criticism may have important
      clinical implications.

PMID- 1987815
TI  - Familial alcoholism in primary unipolar major depressive disorder.
AB  - OBJECTIVE: Some studies have suggested relationships between depression in
      probands and alcoholism in relatives. Other studies have not, but some of these
      have used inappropriate control groups or failed to divide probands by sex.
      METHOD: The present study controlled for sex of probands and used several
      comparison groups to further explore the familial relationship between depression
      and alcoholism. Diagnoses for 723 directly interviewed relatives of 326 probands
      with primary unipolar depression were compared to diagnoses in 469 control
      subjects chosen by an acquaintanceship method to demographically resemble the
      relatives of affective disorder probands. Diagnoses in the uninterviewed
      relatives of both control and depressed subjects were used for comparisons as
      well. RESULTS: Results indicated higher rates of alcoholism in the families of
      depressed women but not in the families of depressed men. CONCLUSIONS: This
      familial association between alcoholism and depression may be the result of
      either genetic or environmental factors or an interaction between the two.

PMID- 1987816
TI  - Less frequent lithium administration and lower urine volume.
AB  - OBJECTIVE: This study was designed to determine whether patients maintained on a
      regimen of lithium on a once-per-day schedule have lower urine volumes than do
      patients receiving multiple doses per day. METHOD: This was a cross-sectional
      study of 85 patients from a lithium clinic who received different dose schedules.
      Patients were admitted to the hospital for measurement of lithium level,
      creatinine clearance, urine volume, and maximum osmolality. RESULTS: Multiple
      daily doses of lithium were associated with higher urine volumes. The dosing
      schedule, duration of lithium treatment, and daily dose of lithium did not affect
      maximum osmolality or creatinine clearance. CONCLUSIONS: Urine volume can be
      reduced by giving lithium once daily and/or by lowering the total daily dose.
      Lithium-induced polyuria seems to be related to extrarenal as well as to renal
      effects.

PMID- 1987817
TI  - Heterogeneity of clinical response during placebo treatment.
AB  - OBJECTIVE: The authors attempted to identify different patterns of improvement
      among patients receiving placebo during clinical trials. It was hypothesized that
      patients who improved abruptly would differ from patients whose improvement was
      gradual in that they would tend to improve earlier and would tend to have less
      persistent improvement. METHOD: The subjects were 144 patients who met the DSM
      III criteria for depressive illness and were randomly assigned to placebo
      medication in four double-blind antidepressant drug trials. All studies lasted 6
      weeks. Mood change was rated each week on a 7-point scale; a rating of 1 or 2 was
      considered an indication of improvement. Improvement was judged to be abrupt if
      the first score of 1 or 2 was immediately preceded by a score of 4 or worse, and
      it was classified as gradual if the first score of 1 or 2 was preceded by a score
      of 3 in at least 1 week. Improvement was considered persistent if a score of 1 or
      2 was not followed by a score of 3 or worse in any subsequent week. RESULTS: Of
      the 144 patients, 72 showed clinical improvement during at least one weekly
      visit; 33 improved abruptly and 39 improved gradually. The abrupt improvements
      occurred significantly earlier in the trial and were less likely to persist than
      the gradual improvements regardless of when they occurred. CONCLUSIONS: These
      data suggest that among patients receiving placebo abrupt improvements are a form
      of placebo response and gradual responses may be the result of spontaneous
      remission. These preliminary observations require validation.

PMID- 1987818
TI  - Different types of placebo response in patients receiving antidepressants.
AB  - OBJECTIVE: The authors studied the responses of drug-treated patients in an
      attempt to validate observations about abrupt and gradual improvements in
      patients receiving placebo. Since previous data suggested that in the first 2
      weeks of antidepressant treatment specific drug effects are unlikely, the authors
      hypothesized that this improvement is a placebo effect. Therefore, in the first 2
      weeks of antidepressant treatment abrupt and gradual improvements should have the
      characteristics of their placebo counterparts. METHOD: The subjects were 263
      patients in controlled antidepressant trials lasting 6 weeks. RESULTS: The
      percentage of abrupt improvements that occurred in the first 2 weeks was higher
      than that for gradual improvements. Abrupt improvements during the first 2 weeks
      of drug treatment were also less persistent than gradual improvements with drug
      and no more persistent than improvements with placebo during the same period.
      However, in weeks 3, 4, and 5, abrupt and gradual improvements with drug were
      equally persistent and both were more persistent than abrupt improvements with
      placebo. CONCLUSIONS: These data support the authors' findings about placebo.
      Abrupt improvements during treatment with both drug and placebo are more likely
      during the first 2 weeks of treatment and are less likely to persist than gradual
      improvements. The fact that persistence of abrupt improvements with drug in weeks
      1 and 2 appears different from that of gradual improvements but appears no
      different after week 3 suggests that the mechanism of action of abrupt
      improvement with drug changes after week 2.

PMID- 1987819
TI  - A national study of psychiatric hospital care.
AB  - BACKGROUND: The delivery system for psychiatric inpatient services in the United
      States has changed dramatically over the past 30 years, undergoing a marked
      privatization. METHOD: To assess the effect of changes in ownership and types of
      inpatient settings on the structure of the mental health services system, the
      authors surveyed a national sample of nonfederal mental health facilities in
      1988. RESULTS: Comparing their data to those of earlier surveys, they found that
      a decline in the number of patients per staff occurred in most settings over the
      last decade, suggesting that this aspect of quality of care may have improved.
      They observed important ownership-related differences in 1988 in diagnostic mix
      (e.g., more schizophrenia treated in public facilities than in private ones) and
      in payer source (e.g., more third-party revenues in public facilities than
      occurred in the past). CONCLUSIONS: There was a significant interaction between
      ownership form and type of facility, suggesting that the type of inpatient
      setting, ownership, and the relation between the two should be considered in
      assessing the impact of privatization on the accessibility of health care
      available for the mentally ill. The authors found that the increase in private
      psychiatric hospitals has widened the availability and choice of treatment
      facilities for those with private funding sources (especially children and
      adolescents) but has not had a similar effect in increasing sources of care for
      the seriously mentally ill dependent upon public financing.

PMID- 1987820
TI  - Disturbed body image in patients with eating disorders.
AB  - OBJECTIVE: The authors attempt to answer the question of whether patients with
      eating disorders experience more distortions in body image than do individuals
      without eating disorders. METHOD: The study group was composed of 214 women out
      of 230 patients consecutively admitted to an inpatient eating disorders program.
      Twelve men and four patients with atypical eating disorders were excluded from
      study. The 214 patients were divided into three groups: 87 with anorexia nervosa
      alone, 72 with anorexia and bulimia nervosa, and 55 with bulimia nervosa alone.
      The comparison group was composed of 61 women drawn from 125 consecutive
      participants in a survey of university students. Fifty-six men were dropped from
      the comparison group, along with eight women who fulfilled diagnostic criteria
      for eating disorders. Each subject used a three-dimensional measure to rate her
      body size and stated her desired body size at seven points: left biceps, left
      calf, left thigh, waist, abdomen, hips, and bust. The subjects' measurements at
      each of these points were taken. Distortion in body image was calculated as the
      subject's perceived body size divided by her actual body size. All subjects were
      also given a battery of tests of intelligence, skill, and memory. RESULTS: All
      three patient groups differed significantly from the comparison group in
      distortions in body image. Most but not all patients with eating disorders had
      distortions in their body image. CONCLUSIONS: If replicated, these findings would
      suggest that the diagnostic criteria regarding disturbance of body image for both
      anorexia and bulimia need to be revised.

PMID- 1987821
TI  - A survey of Canadian psychiatric residents regarding resident-educator sexual
      contact.
AB  - BACKGROUND AND METHOD: A survey of all Canadian psychiatric residents was
      undertaken to ascertain the prevalence of resident-educator sexual contact in
      training programs, the residents' feelings about this contact, their knowledge of
      the ethical standards of the profession, and the extent of the information they
      had been given about this subject. An investigator-designed questionnaire was
      circulated to all psychiatric residents in Canada through the directors of
      postgraduate training programs. To ensure confidentiality, the residents returned
      their questionnaires directly to the investigators. RESULTS: Of the 314
      respondents, 4.1% (N = 6) of the female residents and 1.2% (N = 2) of the male
      residents reported sexual involvements with their educators. Although the
      majority of these eight residents had positive or neutral feelings about the
      contact, 37.5% (N = 3) of the involved residents had mixed feelings. The
      residents' education concerning resident-educator sexual contact was strikingly
      sparse. CONCLUSIONS: This study highlights the need for inclusion of this tissue
      in residency programs.

PMID- 1987822
TI  - The effect of financial management on alcohol-related hospitalization.
AB  - OBJECTIVE: Treatment-unresponsive alcoholics in New Zealand who are unable to
      care for themselves tend to be hospitalized for lengthy periods of time. The
      author examined the effect of adding financial management to the therapeutic
      management of such patients. The null hypothesis was that this would have no
      effect on the duration of alcohol-related hospitalization. METHOD: All 61
      alcoholic patients registered with an alcohol outpatient clinic who received
      financial management over a period of 6 years were included in the study. Their
      alcohol-related disabilities were so severe that they had resulted or were likely
      to result in lengthy or frequent periods of hospitalization. The financial
      management involved putting each patient's income into a checking account for
      which a budget advisory officer was cosignatory for withdrawals. The advisor saw
      to it that patients' basic living requirements were being met and that
      expenditure on alcohol was not having a detrimental effect. Participation was
      voluntary for voluntary patients and involuntary for committed patients. The
      durations of each patient's alcohol-related hospitalizations were compared for
      two equal periods of time before and after financial management was instituted.
      RESULTS: The null hypothesis was not supported. The duration of alcohol-related
      hospitalizations after financial management was instituted was 86% less than it
      was before such management. CONCLUSIONS: For the patient who is struggling in the
      face of excessive drinking to cope with the tasks of daily living, including the
      provision of adequate shelter and nutrition, the benefits of adding financial
      management to other therapeutic strategies should be considered.

PMID- 1987823
TI  - Drug abuse in schizophrenic patients: clinical correlates and reasons for use.
AB  - OBJECTIVE: This study aimed to 1) determine substance abuse prevalence and
      preference in a diverse sample of schizophrenic, schizoaffective, and
      schizophreniform inpatients, 2) compare drug-abusing and non-drug-abusing
      patients on demographic and clinical variables during the acute and stabilization
      phases of their hospital course, and 3) obtain data from patients on reasons for
      drug abuse and on acute state-related changes during periods of intoxication.
      METHOD: Eighty-three psychotic inpatients consecutively admitted to a New York
      City teaching hospital were evaluated. Sixty-eight had schizophrenia, 12 had
      schizoaffective disorder, and three had schizophreniform disorder diagnosed
      according to the Structured Clinical Interview for DSM-III-R. Each patient
      received ratings on the Brief Psychiatric Rating Scale, the Global Assessment
      Scale, and the Scale for the Assessment of Negative Symptoms at admission and at
      discharge, an evaluation of premorbid adjustment, and an extensive interview on
      drug and alcohol use. RESULTS: Forty (48%) of the patients received diagnoses of
      drug or alcohol abuse or dependence. The drug-abusing patients primarily used
      cannabis (N = 26), alcohol (N = 21), and cocaine (N = 14) and reported that they
      abused drugs to get "high," to relieve depression, and to relax. They had
      significantly fewer positive and negative symptoms at discharge, better sexual
      adjustment and worse school performance during adolescence, and more family
      histories of drug abuse than the non-drug-abusing patients. CONCLUSIONS:
      Schizophrenic patients who abuse drugs may represent a subgroup of patients with
      better prognoses and less severe clinical characteristics of schizophrenia, but
      their drug abuse may adversely affect global outcome.

PMID- 1987824
TI  - Hidden severe psychiatric morbidity in sentenced prisoners: an Australian study.
AB  - OBJECTIVE: The aim of this survey was to estimate the prevalence of severe mental
      disorders in a representative sample of sentenced prisoners. METHOD: The subjects
      were selected as a random sample of sentenced prisoners in Melbourne's three
      metropolitan prisons. Interviews were conducted with 158 men and 31 women.
      Clinicians used the Structured Clinical Interview for DSM-III-R (SCID) to
      diagnose psychotic, affective, and substance use disorders. RESULTS: Six
      prisoners (3%) received current diagnoses of psychotic disorders, and 23 (12%)
      were diagnosed as having current mood disorders, mainly major depression. A
      lifetime diagnosis of at least one mental disorder each was made for 82% of the
      respondents, and in 26% more than one lifetime disorder was diagnosed. Sixty-nine
      percent received lifetime diagnoses of dependence on or abuse of alcohol, other
      psychoactive substances, or a combination of these. CONCLUSIONS: These findings
      do not indicate a large-scale shift of deinstitutionalized psychotically ill
      people from mental hospitals to prisons. They do, however, highlight the
      diversion into the corrections system of substance-dependent people and the
      apparent pool of prisoners with largely untreated major depression.

PMID- 1987825
TI  - Familial association between attention deficit disorder and anxiety disorders.
AB  - BACKGROUND AND METHOD: This study tested hypotheses about patterns of familial
      association between attention deficit disorder (ADD) and anxiety disorders among
      356 first-degree relatives of 73 clinically referred children with ADD and 26
      normal comparison children. Through structured diagnostic interviews with trained
      raters, relatives were assessed for adult and childhood psychopathology. After
      stratifying the sample of ADD probands into those with anxiety disorders and
      those without, the authors examined patterns of aggregation of ADD and anxiety
      disorders in the relatives of these probands as well as in the relatives of the
      normal comparison subjects. RESULTS: Familial risk analyses revealed that 1)
      familial risk for anxiety disorders was higher among all ADD probands than among
      the normal subjects; 2) familial risk for ADD was similar in the relatives of the
      ADD probands and of the probands with ADD and anxiety disorder; 3) the relatives
      of the ADD probands with and without anxiety disorders were at greater risk for
      ADD than the relatives of the normal subjects; 4) the risk for anxiety disorders
      was two times higher in the relatives of the probands who had ADD with anxiety
      disorder than in those of the ADD probands without anxiety disorders; and 5)
      there was a tendency for ADD probands' relatives who themselves had ADD to have a
      higher risk for anxiety disorders than ADD probands' relatives who did not have
      ADD (cosegregation). CONCLUSIONS: The results were most consistent with the
      hypotheses indicating that ADD and anxiety disorders segregate independently in
      families.

PMID- 1987826
TI  - An adverse reaction to L-5-hydroxytryptophan.

PMID- 1987827
TI  - Restraining the violent pregnant patient.

PMID- 1987828
TI  - Injunction to cover cost of clozapine.

PMID- 1987829
TI  - Ingestion of sharp foreign objects.

PMID- 1987830
TI  - Services for the homeless mentally ill.

PMID- 1987831
TI  - Elderly patients' decisions about care.

PMID- 1987832
TI  - Anxiety disorders in familial parkinsonism.

PMID- 1987833
TI  - Organic mental disorders caused by HIV.

PMID- 1987834
TI  - Lithium treatment of cocaine addiction.

PMID- 1987835
TI  - Role of cholecystokinin in irritable bowel syndrome.

PMID- 1987836
TI  - Managed care and psychiatry.

PMID- 1987837
TI  - Nutritional treatment of tardive dyskinesia.

PMID- 1987838
TI  - Mechanism for effect of benztropine on bed-wetting.

PMID- 1987839
TI  - Use of "syntonic" to describe a factor common to several disorders.

PMID- 1987840
TI  - Issues related to cults and zealous self-help movements.

PMID- 1987841
TI  - Literature on sun gazing.

PMID- 1987842
TI  - A critical analysis of the largest reported mass fecal occult blood screening
      program in the United States.
AB  - Fecal occult blood testing for the detection of colon cancer remains
      controversial. We performed a mass screening program from January 24, 1988, to
      February 19, 1988, with intensive media promotion, including 121 minutes of
      televised air time. A total of 5,000 primary practitioners were notified by mail.
      Hemoccult-II tests were distributed to 156,000 individuals; 55,051 (35%) were
      returned. Ninety-five percent of the respondents were informed of the program by
      television. A total of 3,375 persons (6%) tested positive for fecal occult blood;
      of these, 2,469 (73%) informed the center that they saw their physician to
      initiate a work-up. Information from physicians regarding work-ups was returned
      on only 1,356 (55%) patients. Diagnostic tests numbered 2,227 (1.6 tests per
      patient). However, 5% had no testing, 16% had a repeat Hemoccult only, and 35%
      had neither a barium enema nor colonoscopy performed. Thirty-six colorectal
      cancers and 212 polyps were identified. The predictive value (i.e., number of
      cancers per number of patients who tested positive) increased directly by decade.
      Thirty-three of 36 patients (92%) with cancer underwent either a barium enema or
      colonoscopy versus only 185 of 438 (42%) patients with a "negative" work-up.
      Cancers found were carcinoma in situ in 10 patients (29%), Dukes A in 12 (35%),
      Dukes B in 4 (12%), and Dukes C in 8 (24%); distant metastases were not found in
      any participant. Thirty-six percent of the tumors were located in either the
      right or transverse colon. We conclude that: (1) Screening identified early
      cancers. All were potentially curable and 64% were limited to the bowel wall. (2)
      Massive Hemoccult distribution was possible over a short interval, but patient
      and physician compliance was disturbingly low. (3) Total colonic evaluation is
      mandatory, since at least 36% of tumors were beyond the reach of the flexible
      sigmoidoscope. (4) Many work-ups were unnecessary (repeat Hemoccults) or
      inadequate, indicating a need for physician education.

PMID- 1987843
TI  - Somatostatin analogue treatment inhibits post-resectional adaptation of the small
      bowel in rats.
AB  - Post-resectional hyperplasia is the phenomenon in which residual small bowel
      increases in size and absorptive capacity after segmental enterectomy. This
      experiment studied the effect of somatostatin analogue therapy on the development
      of two structural parameters of post-resectional hyperplasia in rats subjected to
      40% proximal small bowel resection. Octreotide acetate-treated rats failed to
      develop increased villus height (902 +/- 50 microns) relative to saline-treated
      rats (1,103 +/- 98 microns). Augmentation of residual intestinal weight was also
      significantly impaired in analogue-treated rats (92 +/- 3 versus 118 +/- 5
      mg/cm). We conclude that somatostatin analogue treatment during the early
      postoperative period does impair the growth of residual bowel in rats. These
      findings raise concern regarding the use of this drug for postoperative patients
      who have undergone massive small bowel resection in whom the process of post
      resectional adaptation may be critical to allow sustenance with enteral
      nutrition.

PMID- 1987844
TI  - Surgical management of nonparasitic cystic liver disease.
AB  - We report clinical features, surgical management, recurrences, and follow-up
      study of 12 patients with simple hepatic cyst, 11 patients with polycystic liver
      disease, and 19 patients with cystadenoma who were surgically treated over a 25
      year period. The median age of patients was 48 years, and 37 women and 5 men were
      in the series. The most common presenting symptom and physical finding were
      chronic abdominal pain and tenderness in the right upper quadrant. The most
      commonly associated disease was polycystic kidney disease, which was an
      associated finding in 5 of the 11 patients with polycystic liver disease (45%).
      The most valuable diagnostic studies in all groups were computed tomography and
      ultrasonography. The location of the disease was bilobar in patients with
      polycystic liver disease, with a right lobe predominance in 18% of patients. The
      right lobe was also predominant in 83% of patients with simple hepatic cyst and
      58% of patients with cystadenoma. Of all solitary cystic lesions in the left
      lobe, 75% of them were cystadenomas. Of the 66 surgical procedures performed,
      aspiration was associated with a failure rate of 100%; partial excision, a
      failure rate of 61%; and total excision and liver resection, a failure rate of
      0%. Orthotopic liver transplantation was performed in three patients and was
      associated with two early deaths. Partial excision relieved symptoms in three
      patients (43%) with polycystic liver disease. Total excision, enucleation, or
      liver resection with cyst(s) is the treatment of choice for non-parasitic cystic
      lesions of the liver.

PMID- 1987845
TI  - Factors influencing survival after pancreaticoduodenectomy for pancreatic cancer.
AB  - Eighty-nine patients with carcinoma of the head of the pancreas underwent
      pancreaticoduodenectomies. The actuarial 5-year survival for all 89 patients was
      19%, with a median survival of 11.9 months. The 81 hospital survivors were
      analyzed in an effort to determine factors influencing long-term survival.
      Negative lymph nodes and the absence of blood vessel invasion both favored long
      term survival. The strongest predictive factor was negative lymph node status
      with a median survival of 55.8 months, compared with 11 months with lymph nodes
      involved with tumor (p less than 0.05). Blood transfusions were also predictive,
      with patients receiving two or fewer units having a median survival of 24.7
      months, compared with 10.2 months for those receiving three or more units (p less
      than 0.05). The most important determinant of long-term survival after
      pancreaticoduodenectomy for pancreatic cancer is biology of the tumor (lymph node
      status, blood vessel invasion). However, performance of the resection (units of
      blood transfused) also appears to be an important factor influencing survival.

PMID- 1987846
TI  - Mediators of bile acid-induced alterations in gastric mucosal blood flow.
AB  - The topical application of acidified (pH 1.2) bile acids to acid-peptic-secreting
      gastric mucosa increases mucosal blood flow, an important protective event
      because, when it is blunted, gross mucosal injury occurs. The mediators of this
      response are unknown. The current study examined the potential roles of luminal
      pH, luminal bile acid concentration, and, indirectly, endogenous prostaglandin
      generation in groups of dogs prepared with ex vivo chambered wedges of proximal
      gastric wall. Parameters evaluated included H+ fluxes, mucosal blood flow using
      radiolabeled microspheres, and the severity of gross mucosal injury induced at
      high and low intraluminal pH (7 and 1.2), at differing concentrations of bile
      acid (0, 2.5, 5.0 mM), in the presence of indomethacin pretreatment with or
      without concomitant close intra-arterial infusion of prostacyclin. The results
      indicate that topical bile acids increase mucosal blood flow in proportion to
      their capacity to induce H+ loss. This response is blunted (but not ablated) by
      indomethacin, resulting in gross mucosal injury, effects that are reversed by
      prostacyclin infusion. Thus, in large part, endogenous prostaglandins are its
      likely mediators.

PMID- 1987847
TI  - Quantitative analysis of portal tract infiltrate allows for accurate
      determination of hepatic allograft rejection.
AB  - Changes in the qualitative character of the portal tract infiltrate of hepatic
      allografts can influence the diagnosis of acute rejection. Since qualitative data
      rely on subjective findings, the aim of this study was to perform a quantitative
      analysis of portal tract infiltrates to improve the accuracy of the diagnosis of
      acute rejection. A total of 431 serial hepatic biopsies in 58 consecutive adult
      patients were obtained. The average number of eosinophils, neutrophils, and
      lymphocytes in each portal tract were counted. The area of each portal tract was
      determined using an optical micrometer. Rejection was confirmed by an independent
      investigator using both clinical and histologic criteria. Using a backward
      stepwise logistic regression analysis, we found that eosinophils were the only
      variable predictive of rejection. Using this model, the probability of having
      rejection on a single biopsy can be determined with greater than 90% accuracy.

PMID- 1987848
TI  - Prospective, randomized trial of the biofragmentable anastomosis ring. The BAR
      Investigational Group.
AB  - A randomized trial was undertaken to compare the biofragmental anastomotic ring
      (BAR) with conventional intraperitoneal colorectal anastomotic techniques.
      Patients were randomized into one of two schemes: BAR versus sutured or BAR
      versus stapled anastomosis. There were 782 patients entered into the study and
      283 patients (36%) had a sutured anastomosis, 104 patients (13%) had a stapled
      anastomosis, and 395 (51%) had the BAR. Comparison of the BAR with combined
      suture and stapled controls revealed no significant differences in wound
      complication, abscess rate, bleeding, anastomotic leaks, ileus, obstruction, or
      deaths. There were no differences in return of bowel function, return to normal
      diet, or hospital stay. Intraoperative difficulties occurred in 46 BAR patients
      (17%), and this was significantly higher (p less than 0.001) than for sutured
      (3%) but not for stapled anastomoses (11%). The occurrence of these problems did
      not adversely effect the outcome. The data suggest that the BAR is a safe,
      satisfactory alternative to sutured or stapled colorectal anastomoses.

PMID- 1987849
TI  - Glucose intolerance and hyperinsulinemia of cirrhosis are not results of
      spontaneous or surgical portosystemic shunting.
AB  - To assess if spontaneous portosystemic shunting from collaterals contributes to
      the hyperinsulinemia of cirrhosis, 12 patients with alcoholic cirrhosis underwent
      a 5-hour oral glucose tolerance test 1 day before and 10 days after an elective
      side-to-side portacaval shunt. The glucose, insulin, and C peptide responses to
      oral glucose post-shunt were exaggerated but comparable to preoperative values.
      Compared with preoperative values, the fasting molar ratio of C peptide to
      insulin postoperatively had increased 40% (6.0 +/- 1.2 versus 8.4 +/- 0.7),
      indicating improved hepatic function. These results suggest that extrahepatic
      portosystemic shunting secondary to spontaneous splanchnic collaterals plays
      little or no role in the hyperinsulinemia of cirrhosis. It appears that decreased
      hepatic degradation of insulin in these patients is secondary to hepatocellular
      dysfunction rather than a result of shunting of portal blood around the liver.

PMID- 1987850
TI  - Long-term studies of mental health after the Greenville gastric bypass operation
      for morbid obesity.
AB  - From February 1, 1980, to May 1, 1989, 462 patients underwent the Greenville
      gastric bypass at the East Carolina University School of Medicine. The operation
      effectively maintained satisfactory weight loss after 9 years (mean weight
      preoperatively, 293 lbs; at 24 months, 179 lbs; at 96 months, 194 lbs). The
      gastric bypass favorably affected non-insulin-dependent diabetes, hypertension,
      and physical and role functioning. In the most recent 157 patients, our studies
      were extended to study the effects of the gastric bypass on mental health. The
      significant improvements in mental health indices that were observed 6 and 12
      months after surgery eroded by the end of 2 years. This return of the mental
      health indices to the preoperative status, plus the late occurrence of 3 suicides
      and 2 deaths from alcohol abuse among the total 462 patients, suggest that long
      term follow-up and continued emotional support are essential ingredients for
      successful bariatric surgery.

PMID- 1987851
TI  - Prospective study of a prosthetic H-graft portacaval shunt.
AB  - This study was undertaken to prospectively evaluate the 8-mm Gore-Tex
      interposition H-graft portacaval shunt. Thirty-six high-risk patients at the
      University of South Florida-affiliated hospitals received small-diameter shunts
      because of bleeding esophagogastric varices over a recent 2-year period. Portal
      vein and portal vein-inferior vena cava gradients were significantly reduced
      after shunting. These pressure changes were manifested clinically by the absence
      of variceal rebleeding and improvement of ascites; in addition, the incidence of
      encephalopathy was low. The 8-mm graft maintained hepatopedal flow in 67% of the
      patients, but reversal of flow did not result in complications commonly
      associated with poor portal perfusion. Graft thrombosis occurred in four (11%)
      patients. All grafts were successfully revised, three by operative revision and
      one by an interventional radiologist. Operative mortality was low (11%), and
      morbidity was unusual. The small-diameter H-graft portacaval shunt is a safe and
      effective method of treatment for bleeding esophagogastric varices.

PMID- 1987852
TI  - Immunophenotyping in the management of gastric lymphoma.
AB  - Primary gastric lymphoma is a rare tumor in which surgical resection plays a
      major role in improving the response rate and reducing the incidence of bleeding
      and perforation after chemotherapy. In 17 consecutive patients, the diagnosis of
      gastric lymphoma was made by immunophenotyping snap-frozen endoscopic biopsy
      specimens. All neoplasms were B-cell lymphomas. Pan B surface marker antigens
      were present in all patients. Levels of Ki-67, a nuclear marker of tumor
      proliferation, were greater than 45% in two of the four patients who died after
      progression of their lymphoma. All patients alive had Ki-67 levels of less than
      30%. A lower proliferation index, as measured by Ki-67, appears to be associated
      with better prognosis. Ten of 11 patients treated by resection prior to
      chemotherapy had no complications. Immunophenotyping is the key in the
      differential diagnosis when considering malignant lymphoma with gastric carcinoma
      and benign conditions such as pseudolymphoma.

PMID- 1987855
TI  - The consumption of our heritage.

PMID- 1987854
TI  - A prospective longitudinal study of observation versus surgical intervention in
      the management of necrotizing pancreatitis.
AB  - Pancreatic necrosis is now recognized as a principal determinant of survival in
      acute pancreatitis. However, it is currently unknown how frequently pancreatic
      necrosis develops in acute pancreatitis, how often pancreatic necrosis becomes
      secondarily infected, and whether sterile pancreatic necrosis represents an
      indication for surgery or can be treated by conservative means. In 194 patients
      with unequivocal acute pancreatitis, pancreatic necrosis developed in 38 (20%),
      as documented by dynamic pancreatography, and was confirmed by histologic
      diagnosis at surgery in 28. All patients were prospectively treated by medical
      means. Patients with pancreatic necrosis who remained persistently febrile
      underwent fine needle aspiration for bacterial culture. Infected pancreatic
      necrosis was demonstrated in 27 of the 38 patients (71%) with pancreatic necrosis
      and was treated by open drainage, yielding a mortality rate of 15%. All 11
      patients with demonstrated sterile pancreatic necrosis, including 6 with
      pulmonary and renal insufficiency, were successfully treated without surgery.
      Pancreatic necrosis occurs in approximately 20% of patients with acute
      pancreatitis and is necessary for the development of secondary pancreatic
      infection. However, pancreatic necrosis by itself, even when accompanied by organ
      failure, is not an absolute indication for surgery. A trial of medical treatment
      for all patients with sterile pancreatic necrosis is in order.

PMID- 1987853
TI  - Why does somatostatin cause gallstones?
AB  - Long-term administration of the somatostatin analogue, octreotide, is complicated
      by gallstone formation. Somatostatin is known to inhibit hepatic bile secretion
      and gallbladder emptying. However, the effect of octreotide on gallbladder bile
      composition remains unknown. Therefore, we tested the hypothesis that octretide
      would alter hepatic bile composition and cause gallbladder stasis, thereby
      increasing gallbladder bile solute concentrations. Fourteen control prairie dogs
      received daily saline injections, whereas 10 animals received 1 micrograms of
      octreotide subcutaneously three times per day for 5 days. Cholecystectomy and
      common bile duct cannulation were then performed. Octreotide increased hepatic
      bile concentrations of bilirubin monoglucuronide (p less than 0.05), total
      bilirubin (p less than 0.05), and total protein (p less than 0.01). Rsa, an index
      of gallbladder stasis, was decreased (p less than 0.01) in the octreotide group.
      Gallbladder bile total calcium (p less than 0.05), bilirubin monoglucuronide (p
      less than 0.05), total bilirubin (p less than 0.01), total protein (p less than
      0.05), and total lipids (p less than 0.05) were increased in the octreotide
      group. Animals receiving octreotide also had decreased hepatic (p less than 0.05)
      and gallbladder (p less than 0.001) bile pH. No differences in cholesterol
      saturation index were observed. These data suggest that in the prairie dog,
      octreotide (1) alters hepatic bile composition, (2) causes gallbladder stasis,
      and (3) increases gallbladder bile calcium, bilirubin, protein, lipid, and
      hydrogen ion concentrations. We conclude that octreotide causes alterations in
      gallbladder bile composition that increase the likelihood of cholesterol and
      calcium bilirubinate precipitation.

PMID- 1987856
TI  - Erythromycin enhances delayed gastric emptying in dogs after Roux-Y antrectomy.
AB  - Delayed gastric emptying occurs in up to 50% of patients after truncal vagotomy
      and Roux-Y antrectomy and is often resistant to nonsurgical therapy. This study
      evaluates the effect of erythromycin, metoclopramide, and motilin on delayed
      gastric emptying in four dogs after Roux-Y antrectomy. Solid food gastric
      emptying was measured using a radionuclide technique. Study groups were: (1)
      saline control; (2) erythromycin 1 mg/kg intravenously over 1 hour; (3)
      erythromycin 3 mg/kg by mouth 45 minutes prior to feeding; (4) metoclopramide 0.6
      mg/kg intravenously over 1 hour; and (5) motilin 500 ng/kg intravenously over 1
      hour. After Roux-Y antrectomy, saline control dogs had 73% +/- 5% (SEM) gastric
      retention at 2 hours. After intravenous and oral erythromycin, gastric emptying
      improved at 2 hours to 27% +/- 6% and 39% +/- 5% (p less than 0.01 compared with
      control). Erythromycin intravenously and by mouth improved gastric emptying
      compared with metoclopramide (64% +/- 8%, p less than 0.05). Motilin enhanced
      gastric emptying to a similar degree as erythromycin, with a 2-hour gastric
      retention of 37% +/- 4% (NS). Erythromycin improved gastric emptying in dogs with
      severe Roux-Y gastroparesis and may have clinical application.

PMID- 1987857
TI  - Are pancreatoenteric anastomoses improved by duct-to-mucosa sutures?
AB  - The patency of anastomoses joining the pancreas to either a Roux-Y loop of
      jejunum or the stomach was evaluated in 26 dogs. At a preliminary operation, the
      head and uncinate process of the pancreas were resected while carefully
      preserving the duodenal blood supply. The remaining body and tail of the pancreas
      were totally obstructed. After obstruction for a mean of 22 (range: 6 to 42)
      days, one of three anastomoses was performed: (1) inversion pancreatogastrostomy
      with two layers of sutures; (2) a similar inversion pancreatojejunostomy to the
      side of a Roux-Y jejunal loop; or (3) pancreatojejunostomy in which the major
      duct was joined to the jejunal mucosa with interrupted sutures. Six animals were
      kept for controls. Anastomotic patency was assessed after 8 to 12 weeks by
      pancreatography, with minimal pressures to achieve anastomotic flow recorded.
      Weight trends were consistent with anastomotic status. The eight dogs with duct
      to-mucosa sutures clearly achieved superior anastomotic patency.

PMID- 1987858
TI  - Humoral control of gut function.

PMID- 1987859
TI  - Proximal gastric vagotomy in the emergency treatment of bleeding duodenal ulcer.
AB  - Proximal gastric vagotomy for bleeding duodenal ulcer was performed in 52 low
      risk patients between 1973 and 1986. Duodenotomy without violation of the pylorus
      was done in all patients to allow inspection and control of the bleeding site.
      The median duration of operation was 3 hours and 20 minutes, although 25% of the
      procedures required 4 or more hours. There was no postoperative mortality and no
      early reoperations. Among the six patients with postoperative complications, one
      rebled from the ulcer and two developed prolonged gastric atony. At the time of
      follow-up (median, 2.9 years), 48 of the patients were alive and 4 had died of
      non-ulcer causes. No patient had significant postvagotomy sequelae. Ulcer
      recurrence was documented in six patients, and three required reoperation.
      Proximal gastric vagotomy is a safe, effective therapy for bleeding duodenal
      ulcer. Because of the length of the operation, it should be restricted to low
      risk patients who are hemodynamically stable at the time of operation.

PMID- 1987860
TI  - A 27-year experience with splenectomy for Gaucher's disease.
AB  - Gaucher's disease is an inherited metabolic disorder caused by the defective
      activity of acid beta-glucosidase and the resultant accumulation of glucosyl
      ceramide-laden macrophages in the liver, bone, and spleen. Splenectomy is the
      preferred treatment for patients with Gaucher's disease who develop massive
      splenomegaly with accompanying hypersplenism and/or mechanical pressure symptoms.
      The charts of 48 patients with Gaucher's disease undergoing splenectomy at our
      institution between January 1963 and December 1989 were analyzed to determine the
      short- and long-term results of this procedure. Thirty-five (73%) patients had
      total splenectomy, whereas 13 (27%) patients had partial splenectomy. There was
      one postoperative death (after total splenectomy), and 13 patients (27%) had
      postoperative complications. Eleven patients (23%) presented with accelerated
      bone disease after total splenectomy (mean follow-up: 96 months). No patients
      having partial splenectomy (mean follow-up: 25 months) developed progressive bone
      disease. Eight patients have died since surgery. All four deaths due to malignant
      disease occurred in patients after total splenectomy. The results of this largest
      ever reported series of splenectomy for Gaucher's disease confirm that while
      either total or partial splenectomy can be performed with minimal morbidity and
      mortality, total splenectomy is accompanied by more aggressive bone disease and a
      predisposition to malignancy. Prospective, randomized trials are needed to
      substantiate whether partial splenectomy is indeed the treatment of choice for
      splenomegaly associated with Gaucher's disease.

PMID- 1987861
TI  - Vascular complications after orthotopic liver transplantation.
AB  - Over a 57-month period, we performed 430 orthotopic liver transplants in 372
      patients. A total of 38 vascular complications were identified including hepatic
      artery thrombosis (n = 24), portal vein thrombosis (n = 6), combined hepatic
      artery thrombosis/portal vein thrombosis (n = 3), and hepatic artery rupture (n =
      5). A number of potential risk factors for the development of vascular thrombosis
      were evaluated with only children, weight less than 10 kg, and cold ischemia time
      found to be significant. The clinical presentation included fulminant hepatic
      failure, allograft dysfunction, biliary sepsis, and screening ultrasound. Duplex
      ultrasonography was diagnostic in nearly all cases. Therapeutic modalities
      included revascularization, revascularization followed by retransplantation,
      retransplantation alone, and observation. Five cases of hepatic artery rupture
      occurred in four patients. Infectious arteritis was present in four patients. The
      6-month actuarial survival in patients with vascular complications was 70%. Early
      diagnosis is critical for graft salvage, with surgical intervention the mainstay
      of therapy.

PMID- 1987862
TI  - Manometric and functional comparison of ileal pouch anal anastomosis with and
      without anal manipulation.
AB  - We report the results of postoperative physiologic and functional evaluation of
      153 patients with ileal pouch anal-anastomosis (IPAA). Ninety-nine patients had
      anal manipulation for either mucosal proctectomy, transanal placement pursestring
      suture with stapled IPAA, or handsewn IPAA (manipulation). Fifty-four patients
      had stapled IPAA with anal pursestrings placed transabdominally without
      mucosectomy (no manipulation). Patients with transabdominal anal pursestring
      placement and stapled IPAA without mucosectomy had a higher mean maximum anal
      resting pressure than patients who had endoanal manipulation. This correlates
      with improved continence and a reduced need to wear a pad. Avoidance of anal
      manipulation preserves anal canal resting tone and improves the functional result
      after IPAA.

PMID- 1987863
TI  - High-grade dysplasia in the columnar-lined esophagus.
AB  - Abnormal columnar lining of the esophagus is a well-recognized premalignant
      condition. The management of patients with high-grade dysplasia without evidence
      of carcinoma remains controversial. Esophagectomy is proposed by some
      investigators, whereas others favor follow-up endoscopy and biopsy until
      microinvasive malignancy is documented. We reviewed our experience with nine
      patients referred with high-grade dysplasia on endoscopic biopsies without
      evidence of carcinoma. Eight patients had the columnar lining extending orad from
      the cardia, and one patient had heterotopic columnar epithelium in the cervical
      esophagus. All were white men ranging in age from 19 to 76 years (median: 47
      years). Eight patients underwent esophagectomy with colon interposition. A sleeve
      resection of the cervical esophagus was done in one patient. Multifocal carcinoma
      was found in three patients, all of whom had severe dysplastic changes throughout
      the columnar lining. The patient with heterotopic columnar epithelium had
      microinvasive carcinoma. All four patients with carcinoma had negative nodes and
      are long-term survivors. No carcinoma was found in the resected specimens of the
      remaining five patients. High-grade dysplasia is an important marker of
      malignancy in patients with a columnar-lined esophagus. Esophagectomy is
      indicated in suitable candidates since carcinoma was found in 45% of our
      patients.

PMID- 1987864
TI  - Treatment of allergy to fire ant venom: the (allergy) doctor's dilemma.

PMID- 1987865
TI  - Persistent cough and exertional dyspnea.

PMID- 1987867
TI  - How to review a scientific manuscript.

PMID- 1987866
TI  - Allergens in Hymenoptera venoms. XXIII. Venom content of imported fire ant whole
      body extracts.
AB  - A two-site immunoassay using monoclonal antibodies has been developed to measure
      the imported fire ant venom allergen Sol i III. The assay is specific for
      Solenopsis invicta venom, since one of the monoclonal antibodies does not react
      with Sol r III. A commercial imported fire ant whole body extract, known from
      RAST and skin test data to be potent, was found to contain 10.3 micrograms of Sol
      i III per milliliter. This was comparable to the content of an extract freshly
      prepared in our laboratory. The immunoassay detected Sol i III in an extract of
      fire ant abdomens, but not in head and thorax extract. The amount of imported
      fire ant venom in a potent whole body extract appears to be sufficient to provide
      possible protection for patients receiving it as immunotherapy, although this can
      only be verified by controlled clinical trials with intentional sting challenges.

PMID- 1987868
TI  - Spontaneous cerebrospinal fluid rhinorrhea: a case report.

PMID- 1987869
TI  - Cyclic anaphylaxis associated with menstruation.
AB  - A middle-aged woman developed recurrent episodes of severe life-threatening
      anaphylaxis. All episodes were strikingly associated with the first day of
      menstrual bleeding. Temporary relief was achieved with indomethacin therapy. The
      patient fully recovered following abdominal hysterectomy and salpingoophorectomy.
      The possible role of sex hormones and prostaglandin F2 alpha in the pathogenesis
      of this problem is discussed.

PMID- 1987871
TI  - Abstracts presented at the 47th annual meeting of the American College of Allergy
      and Immunology. November 10-14, 1990, San Francisco, California.

PMID- 1987870
TI  - Emergency room care of asthmatics: a comparison between Auckland and Toronto.
AB  - We compared emergency room visits for the treatment of asthma in two large
      downtown teaching hospitals: one in Auckland, New Zealand and one in Toronto,
      Canada. We wished to determine whether the differences in asthma mortality
      between New Zealand and Canada were reflected in different patterns of emergency
      room use or physician management. Emergency room use during the past decade was
      enumerated in both hospitals, and charts containing the sole diagnosis of asthma
      were reviewed in detail for a defined study period in 1986. In both Toronto and
      Auckland, the number of emergency visits for asthma had increased significantly
      in the past decade (P less than .015 but the rate of rise was significantly
      higher in Auckland (P less than .05). In Auckland, 27% of asthmatics were
      admitted whereas in Toronto significantly fewer (16%) were admitted (P less than
      .0005). Objective measures of pulmonary function were documented more frequently
      by emergency room physicians in New Zealand than in Canada (90% versus 48%; P
      less than .0005). Pulmonary function measurement was primarily by peak flow meter
      in Auckland and most commonly by spirometer in Toronto so that pulmonary function
      measurements could not be compared directly between centers. In both centers,
      however, admitted patients had significantly lower pulmonary function indices
      than discharged patients. In New Zealand, mean peak flow was 38% of the predicted
      value among all asthmatics assessed; in Toronto, mean FEV1 was 47% of predicted.
      In Toronto, pulmonary function measurements were most likely to be missing among
      presumably healthier discharged patients. Pulse rate, respiratory rate, and
      pulsus paradoxus were documented more consistently in Auckland than in
      Toronto.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1987872
TI  - Nonsteroidal anti-inflammatory drug use and increased risk for peptic ulcer
      disease in elderly persons.
AB  - OBJECTIVE: To evaluate the relative risk for peptic ulcer disease that is
      associated with the use of nonaspirin nonsteroidal anti-inflammatory drugs.
      DESIGN: Nested case-control study. SETTING: Tennessee Medicaid program.
      PARTICIPANTS: Medicaid enrollees 65 years of age or older were included in the
      study. The 1415 case patients had been hospitalized for confirmed peptic ulcer
      disease at some point from 1984 through 1986. The 7063 control persons
      represented a stratified random sample of other Medicaid enrollees. MEASUREMENTS
      AND MAIN RESULTS: The estimated relative risk for the development of peptic ulcer
      disease among current users of nonaspirin nonsteroidal anti-inflammatory drugs,
      compared with that among nonusers, was 4.1 (95% CI, 3.5 to 4.7). For current
      users, the risk increased with increasing dose, from a relative risk of 2.8 (CI,
      1.8 to 4.3) for the lowest to a relative risk of 8.0 (CI, 4.4 to 14.8) for the
      highest dose category. The risk was greatest in the first month of use (relative
      risk, 7.2; CI, 4.9 to 10.5). If the association is fully causal, 29% of peptic
      ulcers in the study sample resulted from the use of these drugs, and the excess
      risk associated with such use was 17.4 hospitalizations for ulcer disease per
      1000 person-years of exposure. CONCLUSIONS: These data support other findings
      indicating that a clinically significant risk for serious ulcer disease is
      associated with the use of nonaspirin nonsteroidal anti-inflammatory drugs. The
      data show that this risk increases with dose and recency of use and that use of
      these drugs may be responsible for a large proportion of peptic ulcer disease
      among elderly persons.

PMID- 1987873
TI  - Thoracoscopy for the diagnosis of pleural disease.
AB  - OBJECTIVE: To assess the accuracy and safety of thoracoscopy for the evaluation
      of pleural disease. DESIGN: Prospective evaluation of patients referred for
      thoracoscopy. SETTING: University hospital specializing in chest diseases.
      PATIENTS: We studied 102 patients with pleural disease, the cause of which had
      not been determined after initial investigation, including thoracentesis and
      needle biopsy. Eighty-six patients had pleural effusion, 11 had pleural mass, and
      5 had pleural effusion in association with a known primary lung carcinoma.
      INTERVENTION: All patients had thoracoscopy under local anesthesia with mild
      sedation. Visually directed biopsies were done of parietal pleura. MEASUREMENTS:
      We recorded clinical characteristics, laboratory data, findings and duration of
      thoracoscopy, and any complications associated with the procedure. Hospital and
      clinic follow-up records were reviewed, and patients were contacted by telephone
      12 and 24 months after thoracoscopy to assess their health status. MAIN RESULTS:
      One hundred and four thoracoscopies were done in 102 patients. A definitive
      diagnosis was established in 95 patients: 42 had malignant pleural disease and 53
      had benign pleural disease. A diagnosis of benign pleural disease using
      thoracoscopy could not be confirmed in the remaining 7 patients because of
      insufficient follow-up information. Overall, thoracoscopy was 96% accurate with a
      sensitivity of 91%, a specificity of 100% and a negative predictive value of 93%
      for the diagnosis of pleural malignancy. Thoracoscopy was well tolerated under
      local anesthesia and entailed hospitalization for less than 24 hours in most
      cases. No deaths occurred, although 1.9% of patients had major complications, and
      5.5% had minor complications. CONCLUSIONS: Among patients with pleural disease
      remaining undiagnosed after usual initial investigation, thoracoscopy done under
      local anesthesia is a rapid, safe, and well-tolerated procedure with an excellent
      diagnostic yield that is equivalent to that of thoracotomy.

PMID- 1987874
TI  - Lymphoproliferative responses to Borrelia burgdorferi in Lyme disease.
AB  - OBJECTIVE: To compare lymphocyte proliferative responses to Borrelia burgdorferi
      in healthy controls and patients with Lyme disease. PATIENTS: Twelve patients
      fulfilling case-definition criteria for Lyme disease. Twelve healthy volunteers
      and two newborns served as controls. MEASUREMENTS: Antibodies to B. burgdorferi
      were measured by enzyme-linked immunosorbent assay (ELISA). Proliferation of
      peripheral blood lymphocytes cultured for 5 days with B. burgdorferi, recall
      antigens, or pokeweed mitogen was measured by radioactive thymidine uptake.
      RESULTS: Lymphocytes from 11 patients with Lyme disease, 8 healthy seronegative
      controls, and two newborns showed elevated responses when stimulated with B.
      burgdorferi. When a patient and a control were studied on the same day, the
      patient's lymphocyte response to B. burgdorferi exceeded the control's in only 5
      of 12 cases. Lymphocytes from both patients and controls responded to B.
      burgdorferi isolates from three different sources. CONCLUSIONS: Heightened
      lymphocyte responses to B. burgdorferi are found in patients with Lyme disease
      but elevated responses also frequently occur in healthy controls. At present, the
      interpretation of a positive lymphocyte response to B. burgdorferi would be
      difficult in ambiguous clinical situations.

PMID- 1987876
TI  - Zidovudine-induced macular edema.

PMID- 1987875
TI  - The Munich Gallbladder Lithotripsy Study. Results of the first 5 years with 711
      patients.
AB  - OBJECTIVE: To evaluate the long-term results of three types of shock wave
      treatment in patients with radiolucent gallbladder stones. DESIGN: Cohort study.
      SETTING: Single-center trial. PATIENTS: Of 5824 patients with gallstones, 19%
      were eligible; 711 patients were treated. INTERVENTIONS: Patients received
      extracorporeal shock wave lithotripsy as well as adjuvant therapy with bile
      acids. RESULTS: Lithotripsy was done in three ways, using a water-tank
      lithotriptor (group A), a water-cushion lithotriptor at low energy levels (group
      B), and a water-cushion lithotriptor at high energy levels (group C). The rate of
      complete fragment clearance 9 to 12 months after lithotripsy was done differed
      significantly among the three groups: Among patients with single stones of 20 mm
      or less in diameter, the rate of fragment clearance for group A was 76%; for
      group B, it was 60%; and for group C, it was 83% (P = 0.03). Among patients with
      single stones of 21 to 30 mm, the rate of fragment clearance for group A was 63%;
      for group B, it was 32%; and for group C, it was 58% (P less than 0.005). Among
      patients with two or three stones, the rate of fragment clearance for group A was
      38%; for group B, it was 16%; and for group C, it was 46% (P = 0.01). Patients
      with fragments of 3 mm or less 24 hours after lithotripsy was done showed a
      higher probability of fragment disappearance than did those with larger fragments
      (P less than 0.001). The clearance rate was higher in patients who were compliant
      than in those who were noncompliant with bile acid therapy (P less than 0.001).
      Adverse effects included liver hematoma in 1 patients, biliary pain attacks in
      253 patients (36%), mild biliary pancreatitis in 13 patients (2%), and
      cholestasis in 7 patients (1%). Elective cholecystectomy was done in 16 patients
      (2%), and endoscopic sphincterotomy was done in 4 patients (1%). CONCLUSIONS: The
      rate of complete disappearance of stones after shock wave therapy depends on the
      size and the number of the initial stones, the diameter of the largest fragment,
      and the mode of shock wave treatment. Adjuvant therapy with bile acids appears to
      be important for complete fragment clearance.

PMID- 1987877
TI  - The adverse effect dilemma: quest for accessible information.

PMID- 1987879
TI  - Sepsis, the sepsis syndrome, multi-organ failure: a plea for comparable
      definitions.

PMID- 1987878
TI  - Nonsteroidal anti-inflammatory drugs and peptic ulcer disease.
AB  - Evidence has accumulated that nonsteroidal anti-inflammatory drugs (NSAIDs) cause
      clinically important gastroduodenal ulcers. The pathogenesis, which involves the
      impairment of mucosal resistance to injury in an acid-peptic environment, is
      multifactorial and controversial. Ulcers caused by NSAIDs can occur either in
      mucosa inflamed because of infection with Helicobacter pylori or in
      histologically normal mucosa. The use of these drugs has been linked to an
      unexpectedly high incidence of ulcer complications, and a history of peptic ulcer
      disease is common in such cases. Nonsteroidal anti-inflammatory drugs thus appear
      both to exacerbate an underlying peptic diathesis and to cause de novo ulcers.
      The association between the use of these drugs and ulcer complications is
      supported by ulcer prevalence data from cross-sectional studies, and by data from
      case-controlled and cohort studies, and from randomized, experimental trials.
      Drug-induced gastric ulcers have been prevented by misoprostol, but not by H2
      blocker therapy. Several therapies have been reported to promote ulcer healing
      despite continued use of NSAIDs, but adequate controlled trials have not been
      done. Small gastric and duodenal ulcers readily heal, whereas larger gastric
      ulcers require vigorous and prolonged therapy. The relative efficacies of various
      therapies in preventing ulcers, healing ulcers, or preventing complications
      remain to be established.

PMID- 1987880
TI  - The need to educate physician-scholars for leadership in the health care system.

PMID- 1987881
TI  - Predicting the course of unstable angina.

PMID- 1987882
TI  - Osmolality.

PMID- 1987883
TI  - Alpha-interferon for the hypereosinophilic syndrome.

PMID- 1987884
TI  - Diagnosis of fat emboli.

PMID- 1987885
TI  - Effect of L-thyroxine on bone mass.

PMID- 1987886
TI  - Verapamil toxicity--treatment with hemoperfusion.

PMID- 1987887
TI  - Rhabdomyolysis and simvastatin.

PMID- 1987888
TI  - Chronic pain.

PMID- 1987889
TI  - Coccidia and microsporidia.

PMID- 1987890
TI  - [Relation between aging and cancer].
AB  - Relationship between aging and cancerization is a very interesting problem to be
      clarified in future. As the most important finding in the aged, Tauchi previously
      proposed a decrease in number of the parenchymal cells due mainly to "inhibitory
      factors for cell division", which increase with growth, differentiation,
      maturation and aging of the cells, and for the cancerization he suggested a loss
      of the "inhibitory factors" due to dedifferentiation of the cells. On the growth
      promoting and/or inhibitory factors, some discussions have been made, in relation
      to the immortalization, and cancerization of the cells and also to the aging
      process of them.

PMID- 1987891
TI  - [Distribution of cis-diamminedichloroplatinum in patients with metastatic brain
      tumors after intravenous or intracarotid administration].
AB  - The distribution of cis-diamminedichloroplatinum (CDDP) was studied in 21
      patients with intracerebral metastatic brain tumors from lung cancer after CDDP
      100 mg/sq m i.v. or i.a. administration for 20 minutes using an infusion pump
      during surgery. Surgical tissue specimens of tumor and edematous brain tissue
      adjacent to tumor were obtained with whole blood soon after CDDP administration
      and assayed for total platinum using an atomic absorption spectrophotometer. The
      pharmacological distribution rates were represented as the brain/plasma,
      tumor/plasma and tumor/brain ratios. No statistical differences in the CDDP
      concentrations in the plasma were found between i.a. and i.v. administrations.
      The platinum concentration in edematous brain tissue adjacent to the tumor was
      always lower than the platinum concentration in the metastatic intracerebral
      tumor. No differences were noted for the brain/plasma ratio in the brain tissue
      adjacent to the tumor between the two administration methods (i.a.: 0.38 +/-
      0.09, n = 8; i.v.: 0.43 +/- 0.13, n = 11, M +/- S.E.). However, two cases who
      each underwent two different administration courses showed i.a. to be
      pharmacologically advantageous since it resulted in a 2-to-7 times higher
      concentration in the brain tissue adjacent to the tumor. The tumor/plasma and
      tumor/brain ratios for i.a. administration (1.72 +/- 0.26, 6.09 +/- 1.30, n = 8,
      M +/- S.E.) were two times higher than those for i.v. administration 0.90 +/-
      0.23, n = 12, 3.40 = 0.59, n = 10, M +/- S.E. (p less than 0.05, p = 0.061,
      unpaired t-test). Toxic side effects were moderate, especially decreased
      creatinine clearance, but tolerable. Our preliminary results demonstrated the
      pharmacologic advantage of i.a. CDDP chemotherapy in the treatment of metastatic
      brain tumor patients.

PMID- 1987892
TI  - [A case of aortoduodenal fistula following radiotherapy of retroperitoneal
      metastatic disease].
AB  - A new case of aortoduodenal fistula was added to the five cases previously
      reported in the literature, in which malignancy and/or its treatments could be
      implicated. This 67 year-old woman, six years previously had been placed on a
      therapy including irradiation on the pelvis for cancer of uterine cervix. For
      this time she underwent a radiotherapy completed in a total dose of 55.6 Gy
      combined with hyperthermia and chemotherapy for retroperitoneal metastatic
      disease with excellent response. Three months later she had hematemesis followed
      by melena and deteriorated to hemorrhagic shock. Emergent aortography detected
      contrast extravasation from the aorta with subsequent opacification of the
      duodenum, and immediate intraaortic balloon occlusion was done, but she died soon
      thereafter. Postmortem examination revealed the fistula from the aorta just above
      the bifurcation to a 2 by 1.5 cm. area of the posterior wall of the third portion
      of the duodenum. Accentuated arteriosclerosis in locally irradiated portion of
      the aorta, obstruction of small arteries from organized thrombus and hyaline
      necrosis in the wall of the fistulous tract were defined without evidence of
      tumor invasion. Based upon the findings of the patient reported herein, radiation
      might be another possible etiologic factor in aortoduodenal fistula, as well as
      tumor invasion per se.

PMID- 1987893
TI  - [A tumor sensitivity test, SDI test using XTT].

PMID- 1987894
TI  - [Efficacy of a drug sensitivity test using fosfomycin on human urogenital cancers
      transplanted subcutaneously in nude mice].

PMID- 1987895
TI  - [Study of cisplatin suppository evaluation and clinical significance for local
      chemotherapy of uterine body cancer].

PMID- 1987896
TI  - [Clinical effects of stearyl-ara-CMP (YNK-01) on chronic hematologic
      malignancies].

PMID- 1987897
TI  - [Tumor markers--personal experience. Ha-ras P21 in neuroblastoma: a new marker
      associating to patient's prognosis].
AB  - Neuroblastoma is a disease with wide spectrum clinically For the evaluation of
      the biological specificity of this tumor, we examined the expression of Ha-ras
      p21. The Ha-ras p21 detected in tumor cells showed a statistically significant
      association with the non-progressed tumor at the diagnosis and the favourable
      outcome of the patients. The association of Ha-ras p21 with their clinical
      outcome was closer than those of N-myc amplification. However, the complementary
      analyses of both Ha-ras p21 and N-myc gene seemed to provide more precise
      informations relating the patient's care.

PMID- 1987898
TI  - [Thyroid carcinoma].
AB  - It is now widely accepted that human neoplasms arise as a result of a sequence of
      mutations affecting the structure of genes involved in growth control. In humans,
      indirect measurements based on age dependent tumor incidence predict that, on
      average, the accumulation of 5 to 6 different steps is needed to initiate tumor
      formation. These mutations do not appear to be random, in that certain neoplasms
      show prediction for structural aberrations in specific genes. In thyroid tumors,
      some of gene abnormalities were found. The point mutations of ras oncogenes,
      predominantly H-ras codon 12, are found in 20-25% of follicular adenomas and
      papillary carcinomas. Recently, the gene rearrangements of the oncogenes trk and
      ret were identified in the DNA from papillary carcinomas. About 25% of papillary
      carcinomas contained an introchromosomal (10q) gene rearrangement involving the
      tyrosine kinase domain of the ret oncogene with an unknown amino-terminal
      sequence. The mutations of trk and/or ret were not observed in other thyroid
      neoplastic phenotypes. In medullary thyroid carcinoma, which is a tumor of the
      parafollicular, calcitonin-secreting C cell of the thyroid, approximately 20% of
      patients have autosomal dominant inherited forms. Germ line abnormalities on
      chromosome 10 are linked to at least one type of genetic medullary thyroid
      carcinoma (MEN type 2a). In the present time, the person who has the abnormality
      of gene causing MEN type 2a is able to detect by using DNA marker before the
      onset of tumor.

PMID- 1987899
TI  - [DNA analysis of breast cancer].
AB  - Several methods for DNA analysis including DNA histogram and proto-oncogene
      amplification in human breast cancer, and the results recently reported were
      reviewed. A large number of DNA histograms obtained by flow cytometry have
      provided a possible correlation between DNA ploidy pattern and clinical outcome
      of breast cancer patients. Poor clinicopathologic factors, however, are not
      always in association with DNA aneuploidy and/or S-phase fraction rate,
      suggesting that further investigations on DNA ploidy are required. Amplification
      and/or over expression of proto-oncogenes in human breast cancers have been
      reported. Among them c-erbB-2 amplification may be one of the candidates for
      prognostic indicators of breast cancer survival. To determine any reliable
      biological factors exist further analysis of tumor DNA will be required in breast
      cancer research.

PMID- 1987900
TI  - [DNA diagnosis of human cancers: lymphoid malignancies and leukemia].
AB  - Usefulness of DNA analysis in diagnosis of hematopoietic malignancy was
      discussed. Examination on the presence of rearrangement in immunoglobulin (Ig)
      and T cell receptor (TCR) was the first DNA analysis used for clinical diagnosis
      of lymphoid malignancy to determine the cell-lineage and clonality of
      proliferating lymphoid cells. One point mutation in ras oncogene has also been
      used to detect residual leukemic cells as well as diagnosis of the early relapse
      of leukemia, although not all leukemic cells have this mutation. Presence of BCR
      abl fused gene is a genetic marker for Ph1 chromosome. Analysis of BCR-abl gene
      has made it possible to diagnose the Ph1 ALL and masked Ph1 CML. Development of
      PCR technique markedly increased the possibility for the use of DNA analysis in
      clinical medicine. In addition to Ph1 chromosome, various chromosomal
      abnormalities resulted in a reciprocal translocation between Ig or TCR gene and
      other genes in various lymphoid malignancies, such as Burkitt lymphoma and
      follicular lymphoma. These translocations can be analyzed by Southern
      hybridization and used for clinical diagnosis.

PMID- 1987901
TI  - [Serum deoxythymidine kinase activity in adult T-cell leukemia].
AB  - Serum deoxythymidine kinase activities (s-TK) of the patients with adult T-cell
      leukemia (ATL), carriers and healthy persons were measured, using a recently
      developed TK assay with 125I-iodo-deoxyuridine as a substrate. The mean s-TK
      values were 3.3 +/- 2.7 U/l (n = 21) in normal subjects (HTLV-1(-)), 4.7 +/- 5.0
      U/l (n = 35) in carriers, 9.8 U/l (n = 3) in smoldering ATL and 26.7 U/l (n = 6)
      in chronic ATL. In the patients with acute ATL, the mean s-TK values before and
      after chemotherapy were 80.9 U/l (n = 2) and 11.6 U/l (n = 4), respectively. In
      the follow-up studies of the patients with acute ATL, the changes of s-TK levels
      revealed earlier than those of serum LDH levels. It is suggested that s-TK
      activity is more useful than LDH as a parameter of monitoring treatment in ATL.

PMID- 1987902
TI  - [Clinical application of thymidine kinase activity in patients with acute non
      lymphocytic leukemia].
AB  - An improved method for the detection of thymidine kinase (TK) activity with the
      use of 125I-iododeoxyuridine as the substrate. Radioimmunoassay of prolifigen TK
      "Daiichi", was used for this assay. Eighty-seven serum samples were collected
      from 40 patients with acute nonlymphocytic leukemia in four institutions. The
      levels of TK were measured in the time of pretreatment, remission, and
      recurrence, and the relationship between the levels of TK and either LDH, marrow
      blasts, or circulating blasts was also examined. The levels of TK were
      significantly lower in the state of remission than in the pretreatment. However,
      the level of TK in remission was much elevated in the majority of cases than
      normal range (less than or equal to 5 units/l). On the contrary, LDH in remission
      was within normal limits in the majority of cases. The level of TK in the state
      of relapse was significantly higher than in the remission. The level of TK
      correlated in some extent with the percentage of marrow blasts (r = 0.508), and
      the level of TK in more than 5% of marrow blast was most beyond normal range.
      Correlation coefficient between the percentage of circulating blasts and TK (r =
      0.577) was slightly higher than that between the percentage of marrow blasts and
      TK. Correlation coefficient between the level of TK and the number of marrow
      blasts was higher than that between LDH and number of marrow blasts. The levels
      of TK correlated well with serum LDH (r = 0.778), and was more sensitive than
      LDH. In conclusion, it was suggested that TK could be used as one of an useful
      and supplemental tumor marker in the follow-up of treatment of acute
      nonlymphocytic leukemia and to monitor the effect of therapy.

PMID- 1987903
TI  - [Molecular diagnosis of gastric cancer].
AB  - Molecular mechanism of development and progression of gastric cancer which could
      be a base of molecular diagnosis was described. Amplification and point mutation
      of oncogenes are less common in gastric carcinomas, even though it is valuable
      for diagnosis. Amplification of ERBB2 seems to be an indicator for metastatic
      ability of gastric carcinoma. Overexpression of EGF/receptor system is a biologic
      marker for high malignancy. Diagnostic significance for scirrhous gastric
      carcinomas is found in over-expression of TGF beta, IGF and PDGF. Loss of
      heterozygosity on chromosomes 5q and 17p frequently occurs commonly in well
      differentiated type gastric cancer. More accumulation of molecular alterations in
      the development and progression of gastric cancer should make the molecular
      diagnosis more valuable in clinical field.

PMID- 1987904
TI  - [The effects of Cepharanthin on the recovery of hematopoietic stem cells after X
      ray irradiation].
AB  - Administration of Cepharanthin (ceph) resulted in a significant acceleration of
      the recovery from leukopenia in 5-Gy X-ray irradiated mice. Then we examined the
      function of ceph on the recovery of hematopoietic stem cells after irradiation.
      The number of GM-CFU (granulocyte-macrophage committed stem cells) in the femur
      and spleen increased significantly in ceph compared to phosphate buffer solution
      administered groups. However, the time course of the recovery of GM-CFU did not
      differ between the two groups. These enhancing effects of ceph on GM-CFU were not
      observed when it was added to a bone marrow culture system. Therefore, the
      accelerating effects of the recovery from leukopenia after irradiation appears to
      be an indirect function of ceph.

PMID- 1987905
TI  - [Acute nephrotoxicity by CDDP (on tubular damage)].
AB  - Cisplatin (CDDP) is known to cause a nephrotoxic side effect. By using urinary
      trehalase which is localized renal tubular brush border, we examined an acute
      cisplatin nephrotoxicity. 1) With less than 300 mg of CDDP, urinary trehalase
      activity in the 1st day was significantly increased than preadministration. And
      urinary beta 2-MG was significantly increased in the 2nd day. But urinary NAG was
      not significantly increased. 2) With 300 mg or more of CDDP, urinary trehalase,
      beta 2-MG and NAG were more increased than preadministration. Urinary trehalase
      and beta 2-MG were inclined to increment. But urinary NAG was not inclined to
      decrement. Above all, renal tubular damage is reversible with less than 300 mg of
      CDDP, but is irreversible with 300 mg or more of CDDP.

PMID- 1987906
TI  - [Treatment and prognosis of giant cell tumor in the sacrum--study of Bone Tumor
      Registry in Japan].
AB  - The prognosis of giant cell tumors arising in the sacrum is difficult to
      ascertain. Because of the low incidence in Japan there are scanty statistics. We
      selected 14 cases from the Bone Tumor Registry in Japan. Questionnaires were sent
      to hospitals which had submitted cases, regarding Enneking's staging, surgical
      approach, surgical procedure, radiotherapy, chemotherapy, complications and
      prognosis of this tumor. The results of the questionnaire show that surgery alone
      gives better results than combined surgery and radiotherapy. Good prognosis
      called for surgery alone. Curettage resulted in no evidence of disease (NED) in
      four cases. Bad prognosis called for combined surgery, radiotherapy and
      chemotherapy. If we surmise from the biological behavior of the giant cell tumor,
      that the tumor mass extends out extraosseously en-bloc excision with nerve roots
      is indicated. Extensive curettage will be adequate if the tumor is confined
      intraosseously. Radiotherapy should not be selected except for inoperative cases.

PMID- 1987907
TI  - Proficiency testing of serum enzymes based on medical-needs criteria.
AB  - Proficiency testing goals for serum enzymes have been set by statistical methods,
      by the ex cathedra statements of experts, based on the intraindividual variation
      of healthy people, and based on responses from the users of enzyme data, ie,
      clinicians in practice. Clinicians consider small changes in serum enzyme values
      to be medically unimportant. Medical-needs criteria are probably the most
      relevant in setting proficiency testing goals for enzymes. The enzyme values that
      most modern clinical analyzers are capable of producing are more precise than
      appears to be medically necessary. We surveyed clinicians for their perceived
      needs; based on their responses, we conclude that tight proficiency testing
      limits for enzyme tests are inappropriate.

PMID- 1987908
TI  - Histopathologic features of high-grade non-Hodgkin's lymphomas in acquired
      immunodeficiency syndrome. The French Study Group of Pathology for Human
      Immunodeficiency Virus-Associated Tumors.
AB  - High-grade B-cell non-Hodgkin's lymphomas are observed in 5% to 10% of patients
      with acquired immunodeficiency syndrome. To describe their histologic subtypes, a
      group of pathologists was formed. One hundred thirteen cases were reviewed and
      classified according to the Working Formulation, the updated Kiel classification,
      and a recent description of morphologic variants of high-grade B-cell non
      Hodgkin's lymphoma. Three major types of intermediate- or high-grade lymphomas
      were observed: (1) large-cell or centroblastic mainly polymorphic lymphomas with
      a component of immunoblasts (35 cases); (2) immunoblastic lymphomas with
      plasmablastic and plasmacytic features in most cases (33 cases); and (3) small
      non-cleaved cell Burkitt's or non-Burkitt's lymphoma (41 cases), with 15 cases
      fitting typical criteria of Burkitt's lymphoma and 26 heterogeneous cases in
      which the size and shape of the cells and the presence of plasmablastic features
      varied. The most frequent pathologic sites of involvement at presentation were
      the lymph nodes, gastrointestinal tract, bone marrow, brain, oral cavity, and
      muscles. A comparison between the histologic type and the site of involvement
      showed that most cases involving lymph nodes, bone marrow, or muscles were small
      noncleaved cell Burkitt's or non-Burkitt's lymphomas, while those that affected
      the gastrointestinal tract, brain, and oral cavity were centroblastic or
      immunoblastic lymphomas with consistent plasmacytic differentiation. In 10 cases,
      previous persistent generalized lymphadenopathy syndrome was present. In 13
      cases, the lymphomatous proliferation was associated with follicular or diffuse
      hyperplasia seen on the same lymph node biopsy specimen or in another lymph node.

PMID- 1987909
TI  - Amebic meningoencephalitis in a patient with AIDS caused by a newly recognized
      opportunistic pathogen. Leptomyxid ameba.
AB  - A fatal case of meningoencephalitis due to a leptomyxid ameba in a patient with
      the acquired immunodeficiency syndrome is presented. This opportunistic organism
      has not been previously recognized as a human pathogen. A 36-year-old male
      intravenous drug abuser died after an 18-day hospital course heralded by fever
      and headache and followed by nuchal rigidity and hemiparesis. Computed tomography
      of the head showed multiple hypodense lesions. Neuropathologic examination showed
      that in addition to human immunodeficiency virus encephalomyelitis, there was
      multifocal meningoencephalitis with trophozoites and cysts morphologically
      indistinguishable from those of Acanthamoeba. These organisms were also found in
      the kidneys and adrenal glands. By immunofluorescence, the parasites showed
      antigenic identity with a free-living leptomyxid ameba and failed to react with
      any of a spectrum of antiacanthamoeba antisera. This emphasizes the importance of
      immunofluorescence identification of morphologically indistinguishable ameba
      species.

PMID- 1987910
TI  - Interpretive criteria of the Western blot assay for serodiagnosis of human
      immunodeficiency virus type 1 infection.
AB  - This project was designed to evaluate different criteria used in the
      interpretation of the human immunodeficiency virus type 1 (HIV-1) Western blot
      assay on a group of serum samples blinded to the examiner that were collected
      from individuals attending three different public health departments in central
      North Carolina. Each individual also completed an anonymous linked questionnaire
      regarding sociodemographics and risk factors for blood-borne infections. All of
      the Western blot assays for human immunodeficiency virus type 1 were interpreted
      according to the criteria established at the University of North Carolina
      Hospitals, Chapel Hill, the Centers for Disease Control, Atlanta, Ga, in
      association with the Association of State, Territorial, and Public Health
      Laboratory Directors, Iowa City, Iowa, the American Red Cross, Washington, DC,
      the Consortium for Retrovirus Serology Standardization, Davis, Calif, and the
      Food and Drug Administration, Washington, DC. The results obtained were grouped
      as positive, negative, and indeterminate according to each organization's
      criteria and analyzed in the context of the associated risk factors. The results
      indicate that institutions performing human immunodeficiency virus type 1 Western
      blot confirmatory testing should adopt the criteria of the Centers for Disease
      Control and the State, Territorial, and Public Health Laboratory Directors.

PMID- 1987911
TI  - Enhancement of immunoreactivity among lymphoid malignant neoplasms in paraffin
      embedded tissues by refixation in zinc sulfate-formalin.
AB  - It has been previously demonstrated that improved cytomorphologic detail can be
      obtained from tissue blocks initially fixed in 4% formaldehyde solution by means
      of a "run-back" procedure to an aqueous phase of solution, allowing refixation
      with a protein-precipitating agent, such as zinc sulfate-4% formaldehyde
      solution. Because anecdotal experience with immunostaining such reprocessed
      tissues had suggested improved results, we performed a prospective trial
      involving 13 cases to compare the intensity of immunoreactivity before and after
      such reprocessing. In 10 of 13 cases studied with a variety of antibody reagents,
      we noted a definite improvement of staining, preferentially among those with the
      weakest original immunoreactivity.

PMID- 1987912
TI  - Dipstick analysis of urinary protein. A comparison of Chemstrip-9 and Multistix
      10SG.
AB  - The Boehringer-Mannheim Chemstrip-9 and Ames Multistix-10SG urine dipstick assays
      for the detection of proteinuria were evaluated. Chemstrip-9 was more precise
      than Multistix-10SG (13 inconsistencies vs 32 among duplicate pairs). Precision
      was poorest with the group of inexperienced technologists using Multistix-10SG
      (Chemstrip-9 yielded two inconsistencies vs 15 for Multistix-10SG) with the use
      of urine supplemented with protein standard. In the evaluation of both protein
      supplemented and consecutively acquired patient specimens, Multistix-10SG and
      Chemstrip-9 performed in a statistically similar fashion regarding sensitivity
      and predictive value of a negative test result: supplemented sample sensitivity,
      patient sample sensitivity, and a predictive value of a negative test result of
      90.3%, 46.8%, and 68.6%, respectively, for Multistix-10SG compared with 80.6%,
      31.5%, and 63.5%, respectively, for Chemstrip-9. We conclude that neither test is
      sufficiently sensitive for the detection of low levels of proteinuria (1+ range)
      to function as a screening test for renal disease.

PMID- 1987913
TI  - Cost savings in a hospital clinical laboratory with a pay-for-performance
      incentive program for supervisors.
AB  - A pay-for-performance incentive program for clinical laboratory supervisors was
      developed and implemented at Brigham and Women's Hospital (Boston, Mass). It
      provides monetary rewards to personnel who directly produce cost savings in their
      area of responsibility. This reward system is new to the hospital laboratory but
      is commonly used in industry. Substantial true cost savings over and above
      previously established stringent budgets were achieved, 11% of which was returned
      to first-line supervisors in the form of a bonus. The program expanded the scope
      of professionalism for supervisors to include fiscal management.

PMID- 1987914
TI  - A clinical pathologic study of four adult cases of acute mercury inhalation
      toxicity.
AB  - We report four cases of fatal mercury vapor inhalation, a rare occurrence. The
      mercury vapor was released at a private home, where one of the occupants was
      smelting silver from dental amalgam containing an unknown amount of mercury.
      Within 24 hours of the incident, all occupants began having shortness of breath
      necessitating hospital admission. The clinical courses are briefly detailed;
      however, all included rapid deterioration with respiratory failure. Chest
      roentgenograms in all four cases were consistent with adult respiratory distress
      syndrome. All patients were treated with dimercaprol, a mercury chelator, but all
      died, with survival varying from 9 to 23 days postexposure. Autopsies were
      performed on all four patients. The lungs in all cases were heavy, firm, and
      airless. Histologic examination revealed severe diffuse alveolar damage, with
      variable amounts of fibrosis, conforming with acute lung injury in various stages
      of organization. Additional postmortem findings included acute proximal renal
      tubular necrosis, vacuolar hepatoxicity, and a spectrum of central nervous system
      alterations including multifocal ischemic necrosis, gliosis, and vasculitis.

PMID- 1987915
TI  - Null cell adenoma of the pituitary with features of plurihormonality and
      plurimorphous differentiation.
AB  - The case of a 35-year-old man with pituitary macroadenoma who was complaining of
      reduced sexual activity is presented. Histologic examination showed a
      chromophobic adenoma corresponding mainly to a null cell adenoma at the
      ultrastructural level. Focal plurihormonality and plurimorphous differentiation
      of adenoma cells were demonstrated by immunohistochemical and electron
      microscopic studies. It is suggested that adenomatous null cells represent
      pluripotent progenitor cells capable of transforming to different hormone
      producing cell types. The factors accounting for differentiating to various cell
      populations have yet to be elucidated.

PMID- 1987916
TI  - Regurgitation of fat and marrow emboli into coronary veins during resuscitation.
AB  - Three groups of patients were examined at autopsy for the presence of fat and
      marrow emboli in the lungs, heart, and other organs. Group 1 was composed of
      patients with massive pulmonary thromboembolism and attempted cardiopulmonary
      resuscitation; group 2, patients with pulmonary thromboembolism and without
      attempted cardiopulmonary resuscitation; and group 3, patients without pulmonary
      thromboembolism and with attempted cardiopulmonary resuscitation. The results
      confirm that pulmonary fat and marrow emboli are frequent in those patients who
      are resuscitated. A novel observation is the finding of multiple coexistent
      cardiac venous emboli in those resuscitated patients who have pulmonary artery
      obstruction with pulmonary thromboemboli. These findings suggest that these
      emboli regurgitate from the right side of the heart to the coronary sinus and
      cardiac veins in cases of pulmonary artery hypertension.

PMID- 1987917
TI  - Pleomorphic (anaplastic) neuroblastoma in nude mice.
AB  - Two pleomorphic (anaplastic) neuroblastomas, from two children aged 1 and 6
      years, were transplanted into nude mice. Two noteworthy observations were made.
      In one case, the transplanted tumor gave rise to a soft-tissue sarcoma. Moreover,
      in both cases hepatic metastases were associated with a striking modification of
      murine hepatocytes, resulting in hyperchromatic and dysplastic nuclei. The latter
      finding was particularly evident in the hepatic areas surrounding all metastases
      of pleomorphic (anaplastic) neuroblastoma cells.

PMID- 1987918
TI  - Hemolytic transfusion reaction due to inter-donor kell incompatibility: report of
      two cases and review of the literature.

PMID- 1987919
TI  - Practice parameters.

PMID- 1987920
TI  - Systemic idiopathic fibrosis with T-cell receptor gene rearrangement.
AB  - A case of systemic idiopathic fibrosis was analyzed by Southern blotting with
      probes to the immunoglobulin heavy chain and T-cell receptor genes. A 45-year-old
      man presented with bilateral neck swelling. He later developed lower back pain,
      and findings on a computed tomographic scan were consistent with idiopathic
      retroperitoneal fibrosis. A biopsy specimen of a neck lesion showed morphologic
      characteristics typical of idiopathic fibrosing cervicitis. Immunophenotyping of
      the lesion revealed a polymorphic lymphoid population. Molecular analysis with
      the use of probes to the immunoglobulin and T-cell receptor genes disclosed a
      germline DNA pattern for the immunoglobulin gene and a rearranged pattern for the
      T-cell receptor gene.

PMID- 1987921
TI  - Malignant mixed tumor (malignant ameloblastoma and fibrosarcoma) of the maxilla.
AB  - We present a rare case of carcinosarcoma (malignant ameloblastoma and
      fibrosarcoma) of the left maxilla that developed in a 63-year-old Japanese man.
      The tumor recurred repeatedly despite multiple surgical removals, radiotherapy,
      and chemotherapy and led to progressive cachexia; the patient died after 3.8
      years of hospitalization. Histopathologic examination revealed that the recurrent
      tumor was carcinosarcoma, which had progressed from malignant ameloblastoma with
      fibroma. An autopsy confirmed the diagnosis of malignant mixed tumor with lung
      metastasis of malignant ameloblastoma and fibrosarcoma.

PMID- 1987922
TI  - Bone marrow necrosis in leukemic-phase follicular lymphoma.
AB  - Bone marrow necrosis has been regarded as a rare entity in specimens obtained
      from living patients and has been associated with a poor prognosis. It is most
      commonly found in patients with neoplastic disorders, severe infections, and
      sickle cell anemia. We present an unusual case of a small-cleaved type follicular
      lymphoma associated with bone marrow necrosis and a leukemic phase occurring in a
      55-year-old woman. Specimens were studied by morphologic, immunohistochemical,
      cytogenetic, and DNA hybridization techniques.

PMID- 1987923
TI  - Fatal embolization of intestinal contents through a duodenocaval fistula.
AB  - Embolization of intestinal contents to the lung is an exceedingly rare event,
      which to our knowledge, has never been reported as a cause of death. Equally rare
      is duodenocaval fistula resulting from a penetrating duodenal peptic ulcer. We
      present the case of a 51-year-old man whose duodenal ulcer led to a fistulous
      tract with the inferior vena cava and subsequently to progressive pulmonary
      embolization of intestinal contents, ultimately resulting in death from
      respiratory failure.

PMID- 1987924
TI  - Plastic embedding of unfixed tissues following freeze substitution. New
      techniques permitting preservation of labile antigens and enzymatic activity.

PMID- 1987925
TI  - Aspergillus terreus endophthalmitis in a patient with chronic lymphocytic
      leukemia.
AB  - A 65-year-old woman with a 7-year history of chronic lymphocytic leukemia
      presented with acute visual loss, pain, and redness in her right eye. Results of
      stains and cultures of anterior chamber fluid were negative. Neurologic problems,
      bronchopulmonary pneumonia, recurrent skin lesions, and a low-grade fever
      developed. Progressive respiratory distress ensued, and the patient died 1 month
      after presentation. Cultures from antemortem sputum and skin samples were
      positive for Aspergillus terreus. Postmortem histologic results showed extensive
      A terreus invasion of the posterior vitreous, retina, choroid, and anterior optic
      nerve. This organism was also found in histologic sections from the right adrenal
      gland, left kidney, thyroid, urinary bladder, right lung, skin, esophagus,
      sputum, vessels of the myocardium, and brain. To our knowledge, A terreus
      endophthalmitis has not been reported previously.

PMID- 1987926
TI  - The incidence of ulcerative keratitis among aphakic contact lens wearers in New
      England.
AB  - We conducted a population-based incidence study in five New England states to
      quantify the risk of ulcerative keratitis associated with contact lens use among
      aphakic persons. All practicing ophthalmologists in the five-state area were
      surveyed to identify prospectively all new cases of ulcerative keratitis during a
      4-month period. The number of aphakic persons using specific types of contact
      lenses was estimated through a telephone survey of 4178 households identified by
      random digit dialing. The annualized incidence of ulcerative keratitis among
      aphakic persons using contact lenses was estimated to be 52 cases per 10,000
      aphakic contact lens wearers (95% confidence interval (CI), 31.1 to 86.9). The
      risk of ulcerative keratitis varied substantially by lens use, with extended wear
      having an estimated sevenfold greater risk relative to daily wear (95% CI, 1.6 to
      30.2). Rates of ulcerative keratitis in aphakic persons using contact lenses were
      much greater than rates among cosmetic wearers of the same lens type: for daily
      wear lenses, aphakic persons were estimated to have 6.3 times the risk of
      cosmetic wearers (95% CI, 1.9 to 21.0), and for extended-wear lenses, aphakic
      persons were estimated to have 8.7 times the risk of cosmetic wearers (95% CI,
      3.5 to 21.9). These risks are useful in assessing the benefits and risks of
      contact lens wear as an alternative to other methods of aphakic correction.

PMID- 1987927
TI  - Limitation of retinal injury by vitreoperfusion initiated after onset of
      ischemia.
AB  - We tested whether vitreoperfusion, a new method of perfusing the vitreous cavity
      with solutions containing nutrients, can limit retinal injury if initiated after
      the onset of ischemia. Severe bilateral ocular ischemia was induced in cats with
      healed lensectomy-vitrectomy wounds; 30, 60, 90, or 120 minutes later, one eye
      from each of 18 cats underwent vitreoperfusion while the ischemia continued for
      120 minutes. The other eye simultaneously underwent either continued untreated
      ischemia or reinstated circulation. The histopathologic abnormalities evident
      after 8 days depended on the duration of ischemia. Reinstated circulation yielded
      less retinal damage than continued ischemia. Nine additional cats underwent
      bilateral ischemia for at least 210 minutes. Vitreoperfusion was initiated in one
      eye after 30 minutes. In each cat, the vitreoperfused eye fared significantly
      better as observed histopathologically and electroretinographically. We believe
      that no other treatment has similarly limited retinal injury in vivo when
      initiated so long after total ocular ischemia has developed.

PMID- 1987928
TI  - Acepromazine. Effects on intraocular pressure.
AB  - We investigated the effects of the topical application of acepromazine maleate on
      the intraocular pressure (IOP) in 27 adult rhesus monkeys. The monkeys were
      divided into two groups: group 1 (16 monkeys) had both eyes normal, and group 2
      (11 monkeys) had experimental chronic glaucoma in one eye and a normal fellow
      eye. One drop of 1% acepromazine maleate solution was instilled in one eye of
      monkeys in group 1 and in the glaucomatous eye of monkeys in group 2; the other
      eye served as the control. The IOP was measured before drug administration and 1,
      4, 8, 24, and 32 hours after, with detailed slit-lamp examination of the anterior
      segment. Acepromazine produced no change in IOP in eyes in group 1, but it
      produced a fall in pressure in all eyes with high IOP in group 2, evident 1 hour
      after instillation, maximal between 4 and 8 hours, and still remaining after 32
      hours. The pupil showed no change in size, but a transient ptosis was observed in
      the treated eye in all monkeys.

PMID- 1987929
TI  - Remission of anterior uveitis by subconjunctival fluorouracil.

PMID- 1987930
TI  - Exudative retinal detachment after photodynamic injury.
AB  - Exudative retinal detachments occur in a variety of retinal and choroidal
      diseases. We created serous retinal detachment in the cat eye by means of
      photodynamic injury produced by activation of intravascular rose bengal using
      filtered, focused light (550 nm). Fluorescein angiography later revealed focal
      retinal and choroidal vascular occlusion surrounded by a larger area of leakage
      through the pigment epithelium. Serous retinal detachments occurred rapidly,
      gradually enlarged over the next 3 days, and resolved in all eyes after 14 to 21
      days. Histopathologic and ultrastructural features of early lesions included the
      accumulation of proteinaceous fluid in the subretinal space, pigment epithelial
      cell damage, and localized occlusion of retinal vessels and the choriocapillaris.
      Later changes consisted of limited regeneration of the retina and portions of the
      tapetum. In several respects, these experimental detachments resemble the serous
      retinal detachments associated with choroidal ischemia in humans, and may serve
      as a useful model in the study of choroidal microvascular hypoperfusion.

PMID- 1987931
TI  - Visual acuity and field loss in retinitis pigmentosa.

PMID- 1987932
TI  - Synophthalmia and holoprosencephaly in chromosome 18p deletion defect.

PMID- 1987933
TI  - Conjunctival retraction suture for fornix adjustable strabismus surgery.
AB  - The fornix approach to strabismus surgery is advantageous because the incision is
      made under the eyelid, there is no need for conjunctival sutures, it is
      comfortable for the patient, and there is minimal postoperative scarring. The
      major disadvantage of the fornix approach for the adjustable suture technique has
      been poor exposure to the muscle-suture apparatus and poor postoperative knot
      exposure. We describe herein the use of a subconjunctival retraction suture for
      adjustable suture surgery with the fornix approach. This suture retracts the
      conjunctiva, exposing the adjustable muscle-suture apparatus while simultaneously
      fixating the globe. A novel way of tying the noose around the pole sutures and
      preventing noose slippage is also presented. This technique provides excellent
      exposure, fixation of the globe, and complete coverage of the knot with
      conjunctiva after adjustment.

PMID- 1987934
TI  - A simple device for laser suture lysis after trabeculectomy.

PMID- 1987935
TI  - A new inexpensive pump for vitreoretinal surgery.
AB  - An inexpensive and reliable fluid-gas exchange system has been developed for
      vitreous surgery. The system relies on a fish-tank air pump and was compared with
      the Grieshaber Air System in several laboratory and operating room situations. No
      significant differences were found between the two systems. Details of the Davis
      Ocular Air Pump are provided along with a cost analysis.

PMID- 1987936
TI  - A new self-sealing needle for iris suture fixation.

PMID- 1987937
TI  - Excimer laser in monkeys.

PMID- 1987938
TI  - Postoperative corneal edema secondary to a free fragment of Descemet's membrane.

PMID- 1987939
TI  - Spontaneous Descemet's membrane tear and detachment.

PMID- 1987940
TI  - Spontaneous collapse of a primary iris cyst associated with an iris nevus.

PMID- 1987941
TI  - Brown-McLean syndrome.

PMID- 1987942
TI  - Rhegmatogenous retinal detachment treated by continuous vitreous insufflation.

PMID- 1987943
TI  - $8.7 billion in Medicare savings to come from physician fees.

PMID- 1987944
TI  - The Association of University Professors of Ophthalmology. Facilitation and
      interaction.

PMID- 1987945
TI  - Topically active carbonic anhydrase inhibitors for glaucoma.

PMID- 1987946
TI  - Vision research in departments of ophthalmology. An Association of University
      Professors of Ophthalmology perspective.
AB  - A research committee of the Association of University Professors of Ophthalmology
      disseminated a survey questionnaire to determine the state of research in
      departments of ophthalmology across the United States. The questionnaire
      contained 71 questions that were designed to assess attitudes and trends within
      members' departments and to solicit suggestions from the membership. Of the 145
      members and affiliates queried, 140 responded. While the results of the survey
      indicate significant diversity among departments, departmental chairpersons view
      research as a major priority in the goals of their departments, and they envision
      maintenance or expansion of research over the next decade. The survey results
      have been collated and serve now as the basis for this Association of University
      Professors position article.

PMID- 1987947
TI  - Multiple-dose, dose-response relationship for the topical carbonic anhydrase
      inhibitor MK-927.
AB  - The multiple-dose, dose-response curve of MK-927 was studied in a five-center,
      double-masked, randomized, placebo-controlled, parallel study of 2%, 1%, and 0.5%
      MK-927 in 76 patients with bilateral primary open angle glaucoma or ocular
      hypertension and intraocular pressure greater than 24 mm Hg following washout of
      ocular hypotensive medications. Patients received doses at 8 AM and 8 PM for 14
      days, and parallel 12-hour intraocular pressure curves were performed prestudy
      and on day 14, with 4-hour curves on days 1 and 4. There was a significant dose
      response relationship, with 0.5% MK-927 twice daily being a minimal-effect dose.
      Both 1% and 2% MK-927 were active through 12 hours postdose, and peak mean
      percent decrease in pressure at 2 hours postdose was 18.6% and 20.6%,
      respectively.

PMID- 1987948
TI  - Multiple-dose efficacy comparison of the two topical carbonic anhydrase
      inhibitors sezolamide and MK-927.
AB  - The multiple-dose twice-daily efficacy of the topical carbonic anhydrase
      inhibitor MK-927, a racemic compound, was compared with that of its
      pharmacologically more active S-enantiomer in a four-center, double-masked,
      randomized, placebo-controlled, parallel study of 1.8% sezolamide hydrochloride
      (MK-417), 2% MK-927, and placebo, given twice daily to 48 patients with bilateral
      primary open angle glaucoma or ocular hypertension and morning intraocular
      pressure greater than 24 mm Hg in both eyes following washout of ocular
      hypotensive medications. Parallel 10-hour modified diurnal curves were performed
      before the study and on day 14, with 4-hour curves on days 1 and 4. Both
      compounds demonstrated significant lowering of intraocular pressure at 8 AM, 12
      hours following the evening dose, and through 10 and 6 hours following the 8 AM
      dose for sezolamide and MK-927, respectively. Morning trough (evening) activity
      as measured by mean percent change in intraocular pressure from prestudy was 
      9.2% for sezolamide and -11.1% for MK-927 (-13.5% and -9.6%); peak effect
      occurred 2 hours after dose administration and was -19.4% and -19.2% for
      sezolamide and MK-927, respectively. From 2 hours after dose administration,
      sezolamide consistently demonstrated a slightly greater decrease in intraocular
      pressure than MK-927; however, these differences were not statistically
      significant.

PMID- 1987949
TI  - Endophthalmitis from contaminated donor corneas following penetrating
      keratoplasty.
AB  - We encountered six (0.2%) cases of endophthalmitis resulting from contaminated
      donor corneas between January 1983 and July 1990 following a total of 3000
      consecutive penetrating keratoplasties. Causative organisms in the three cases of
      fungal endophthalmitis were Torulopsis glabrata, Candida albicans, and
      Aspergillus flavus; the three cases of bacterial endophthalmitis were due to
      Klebsiella pneumoniae, Staphylococcus aureus, and Enterococcus faecalis. All
      organisms were resistant to gentamicin in the preservation media. A significantly
      higher incidence of endophthalmitis was noted in patients receiving corneas from
      a Sri Lankan eye bank (1.25%) than in those receiving US eye bank tissue (0.14%).
      Donor rim cultures are important to identify those patients at increased risk of
      developing endophthalmitis, enabling earlier diagnosis and more specific
      treatment should endophthalmitis occur.

PMID- 1987950
TI  - Chronic postoperative endophthalmitis associated with Actinomyces species.
AB  - Actinomyces species, gram-positive, non-spore-forming anaerobic bacilli were
      isolated from intraocular fluid obtained from four otherwise healthy patients
      with a delayed onset of postoperative endophthalmitis. One patient had a mixed
      anaerobic infection with recovery of both Actinomyces israelii and
      Propionibacterium acnes. In all four patients, early postoperative visual acuity
      was good but was eventually markedly reduced by intraocular inflammation that was
      first observed between 21 days and 4 months following uneventful extracapsular
      cataract extraction and posterior chamber intraocular lens implantation.
      Inflammation was characterized by anterior segment and vitreous cellular debris
      in all cases. All eyes responded to therapy that included intraocular, topical,
      and systemic antibiotics as well as pars plana vitrectomy and partial iridectomy.
      These cases further illustrate the need for microbiologic investigation,
      including anaerobic cultures, in all cases of chronic postoperative inflammation
      following extracapsular cataract extraction, regardless of the time of onset.

PMID- 1987951
TI  - Penetrating ocular injury from contaminated eating utensils.
AB  - Although the rate of infectious endophthalmitis following penetrating ocular
      injury is generally less than 10%, certain settings may carry a greater risk of
      infection. One such setting is penetrating injury resulting from eating utensils
      contaminated with oral flora. We reviewed six of these injuries. Culture-positive
      bacterial endophthalmitis developed in four of the six eyes; only one of the eyes
      retained reading visual acuity (greater than 20/50) and two eyes lost light
      perception. The potential for infection and limited visual outcome in this series
      warrants aggressive prophylaxis and treatment. The unexpected isolation of
      Haemophilus influenzae in two of the four infections suggests that broad-spectrum
      antibiotic treatment should be considered in all such injuries since less common
      organisms may be encountered.

PMID- 1987952
TI  - Systemic sulfonamides as a cause of bilateral, anterior uveitis.
AB  - Between September 1976 and May 1989, 12 cases of uveitis attributed to the
      systemic use of sulfonamide derivatives were reported to the National Registry of
      Drug-Induced Ocular Side Effects and the US Food and Drug Administration. We
      evaluated these reports in addition to one case previously reported in the
      literature and one patient seen at the Uveitis Clinic, Oregon Health Sciences
      University, Portland. The patients' median age was 34 years. Twelve of 14
      patients were treated with trimethoprim-sulfamethoxazole. All patients for whom
      the location of the eye disease was specified presented with an iritis. Six
      reports included a description of ocular symmetry, with all patients having
      bilateral inflammation. Of the nine patients for whom data on the duration of
      drug use was available, seven experienced adverse effects within 8 days of
      beginning trimethoprim-sulfamethoxazole therapy and four showed effects within 24
      hours. Three patients had histories of rechallenge with trimethoprim
      sulfamethoxazole, and in each case acute iritis recurred within 24 hours of
      reinstitution of therapy. Five patients had additional evidence of an adverse
      reaction manifested as Stevens-Johnson syndrome, erythema multiforme, diffuse
      macular or vesicular rashes, stomatitis, glossitis, conjunctival and scleral
      injection, and granulomatous hepatitis. The consistent presentation including
      bilateral, anterior inflammation and the recurrence with rechallenge strongly
      indicate a cause-effect relationship. Although uveitis secondary to sulfonamides
      is a rarely diagnosed clinical event, recognition of the distinct presentation of
      this entity is important in the differential diagnosis of uveitis.

PMID- 1987953
TI  - The relationship of visual acuity, refractive error, and pupil size after radial
      keratotomy.
AB  - To better define the relationship between residual refractive error, uncorrected
      visual acuity, and pupil diameter, we compared 42 eyes that had an eight-incision
      radial keratotomy according to the Prospective Evaluation of Radial Keratotomy
      Study protocol with 42 matched control eyes. The parameters measured were best
      corrected visual acuity, uncorrected visual acuity, and the change in cycloplegic
      refraction with enlarging pupil diameter. The best corrected visual acuity was
      20/16 in both the radial keratotomy and control groups, but the variability (SD)
      was higher in the radial keratotomy group. The average uncorrected visual acuity
      was 0.35 (35%) better in the radial keratotomy group, but the variability was
      1.77 times higher. Change in refraction with dilation occurred in 9% of the
      controls and 36% of the radial keratotomy patients, indicating a significant
      difference (P = .002). The change in refraction with dilation in the eyes with
      radial keratotomy was almost equally split between a hyperopic change (17%) and a
      myopic change (18%), which was much different than in the control eyes, only 2%
      of which changed in a hyperopic direction and 7% in a myopic direction. The
      radial keratotomy patients with a myopic change had the best uncorrected visual
      acuity, indicating that positive spherical aberration yielded the best aspherical
      surface for uncorrected visual acuity.

PMID- 1987954
TI  - Clinically detectable nerve fiber atrophy precedes the onset of glaucomatous
      field loss.
AB  - Standardized perimetry and nerve fiber layer and color fundus photography were
      performed annually on 1344 eyes with elevated intraocular pressures. In 83 eyes,
      glaucomatous field defects developed that met rigid criteria on manual kinetic
      and suprathreshold static perimetry. Individual nerve fiber layer photographs
      were read by two masked observers. The more sensitive of the two identified nerve
      fiber layer defects in 88% of readable photographs at the time field loss first
      occurred; 60% (6/10) of eyes already had nerve fiber layer defects 6 years before
      field loss. In contrast, the nerve fiber layer was considered abnormal in only
      11% (3/27) of normal eyes and 26% (84/327) of hypertensive eyes. The location of
      nerve fiber layer and field defects closely corresponded, but nerve fiber layer
      loss was generally more widespread. Examiner experience and severity of optic
      nerve damage influenced results. Mild focal defects were more readily recognized
      than more severe diffuse atrophy. Nerve fiber layer defects expanded with time,
      often by the development and coalescence of adjacent areas of damage.

PMID- 1987955
TI  - Autosomal dominant sectoral retinitis pigmentosa. Two families with transversion
      mutation in codon 23 of rhodopsin.
AB  - A cytosine-to-adenine transversion in codon 23 of rhodopsin, the rod visual
      pigment gene, was reported recently by Dryja et al in 17 of 148 unrelated
      patients with autosomal dominant retinitis pigmentosa, but the clinical findings
      associated with this deletion have not been reported in detail. In screening our
      patients with autosomal dominant retinitis pigmentosa for the codon 23
      transversion, we found positive results in four affected individuals from two
      families with sectoral retinitis pigmentosa, while 12 patients with sectoral
      retinitis pigmentosa from different families had negative results, suggesting
      that other gene sites or locations may give this same phenotypic change. From our
      patients' history of light exposure and the location of degeneration in the
      retina, we hypothesize that light phototoxicity may be playing an expressive role
      in this point mutation of the rhodopsin gene. This is the first report in which a
      type of retinitis pigmentosa has been associated with a specific molecular gene
      defect, although the actual pathophysiologic mechanism currently is unknown.

PMID- 1987956
TI  - Ocular findings in patients with autosomal dominant retinitis pigmentosa and a
      rhodopsin gene defect (Pro-23-His).
AB  - Ocular findings are presented from 17 unrelated patients with a form of autosomal
      dominant retinitis pigmentosa and the same cytosine-to-adenine transversion in
      codon 23 of the rhodopsin gene corresponding to a substitution of histidine for
      proline in the 23rd amino acid of rhodopsin (designated rhodopsin, Pro-23-His).
      On average, these patients (mean age, 37 years) had significantly better visual
      acuity and larger electroretinographic amplitudes than 131 unrelated patients
      (mean age, 32 years) with autosomal dominant retinitis pigmentosa without this
      mutation. However, these 17 patients from separate families, as well as 12
      relatives with the mutation from four of these families, showed interfamilial and
      intrafamilial variability with respect to severity of their ocular disease,
      suggesting that some factor(s) other than this gene defect itself is involved in
      the expression of their condition. This form of retinitis pigmentosa can now be
      detected by testing leukocyte DNA from peripheral blood. Some mechanisms by which
      this mutation in the rhodopsin gene could lead to rod photoreceptor cell death
      are suggested.

PMID- 1987957
TI  - Blood velocity waveforms in the fetal aorta and umbilical artery as predictors of
      fetal outcome: a comparison.
AB  - In 139 pregnancies in which intrauterine growth retardation (IUGR) was suspected
      at routine ultrasound screening at 32 weeks of gestation, blood velocity in the
      fetal aorta and umbilical artery was recorded by a pulsed Doppler ultrasound
      every second week until delivery. The maximum blood flow velocity waveforms
      (FVWs) were analyzed for pulsatility index (PI) and blood flow class (BFC). In
      both vessels, an abnormal PI (greater than mean + 2 SD of the normal population)
      and abnormal BFC at the final antenatal examination were significantly associated
      with the occurrence of IUGR (birthweight less than or equal to mean - 2 SD) (p
      less than 0.001), operative delivery for fetal distress (p less than 0.001), and
      a low 1-minute Apgar score (less than or equal to 7). PI in the umbilical artery
      was a better predictor of fetal outcome than was the aortic PI, but the BFC was
      similarly predictive of fetal outcome in both vessels. The data indicate that a
      simple umbilical artery examination, which can be performed blindly with the
      Doppler ultrasound instrument without the help of a real-time scanner, is a
      reliable method for monitoring fetal status in pregnancies when IUGR is
      suspected.

PMID- 1987958
TI  - Effect of pregnancy on glucose metabolism in glucose intolerant 'BB' Wistar rats.
AB  - Little is known about the effect of pregnancy on the 'BB' Wistar rat, an animal
      model of insulin-dependent (type I) diabetes. The pathogenesis of diabetes in
      this animal model seems to result from antibody-mediated natural killer cell
      destruction of pancreatic beta cells. The glucose metabolism of glucose
      intolerant female rats (study group) was studied prior to pregnancy, during
      pregnancy, and postpartum using glucose tolerance tests (GTT). Control rats with
      normal GTT were studied and bred in a fashion similar to the study animals.
      Before becoming pregnant, the GTT levels of the chemically diabetic rats were
      significantly different from those of the controls (p less than 0.05). The GTT
      values of the study animals decreased during pregnancy to levels seen in pregnant
      controls. After pregnancy, the GTT values of the study animals returned to
      prepregnant levels. Based on these observations, it appears that pregnancy may
      block the autoimmune destruction of beta cells, causing an increase in insulin
      production and release, thereby improving glucose metabolism.

PMID- 1987959
TI  - Prenatal diagnosis of tetralogy of Fallot with absent pulmonary valve.
AB  - Multiple indications for fetal echocardiography have been proposed that includes
      polyhydramnios. In this report, the prenatal diagnosis of tetralogy of Fallot
      with absent pulmonary valve and absent ductus arteriosus was made in a patient
      presenting with polyhydramnios. Tracheobronchial and esophageal compression
      secondary to gross dilation of the pulmonary artery is considered the etiology of
      the polyhydramnios, and in the case of this structural defect is an indicator of
      poor prognosis.

PMID- 1987960
TI  - Sonography of unilateral megalencephaly in the fetus and newborn infant.
AB  - A 27-year-old primigravida women was referred for ultrasound studies at 32 weeks'
      gestation because of the suspicion of fetal ventriculomegaly. Sonographic
      examination of the fetal brain found a marked shift of the midline, with enlarged
      left hemisphere and ipsilateral occipital horn, and abnormal convolutions. A 3500
      gm male infant was delivered by cesarean section at 39 weeks' gestation because
      of worsening macrocrania after which the diagnosis of unilateral megalencephaly
      was confirmed by computed tomography.

PMID- 1987961
TI  - Effects of gestational weight gain in morbidly obese women: I. Maternal
      morbidity.
AB  - Current recommendations for appropriate weight gain in pregnancy suggest an
      optimum of 120% of ideal body weight (IBW) at delivery. This represents an
      increase of approximately 24 pounds in the normal weight woman and even the obese
      patient (more than 135% IBW) is told to gain 16 pounds. Information concerning
      gestational weight gain in the morbidly obese woman (more than 160% IBW) has not
      been reported. We evaluated 40 morbidly obese pregnant women for maternal
      morbidity relative to gestational weight gain. No correlation was found between
      maternal weight gain and the development of gestational diabetes, pregnancy
      induced hypertension, preeclampsia, preterm labor, premature rupture of
      membranes, incompetent cervix, or intrauterine growth retardation. The incidence
      of primary cesarean delivery was statistically greater in those women gaining
      more than 24 pounds (p less than 0.05). It appears that current recommendations
      for gestational weight gain in the morbidly obese are excessive and may result in
      increased maternal risk.

PMID- 1987962
TI  - Bacterial contamination of human milk: container type and method of expression.
AB  - Common questions from nursing women include: is the bacterial contamination of
      expressed milk different if collected manually versus mechanically and is there a
      large increase in bacterial contamination if the milk is collected into clean
      versus sterile containers. Similarly, there are mixed reports, and secondarily
      confusion, among lactating women regarding the benefit of discarding the initial
      portion of a milk expression to limit bacterial contamination with skin flora. To
      answer these concerns, we have measured the number of colony-forming units
      (CFU)/milliliter in expressed milk from 16 women. The experimental design, used
      in a randomized fashion with each woman, employed both sterile and clean
      containers for collection and both the manual and mechanical techniques for milk
      expression. The number of milk specimens containing greater than 10(4) CFU/ml was
      not different between those collected in clean versus sterile containers or
      between those collected with a manual versus a mechanical technique. Finally, the
      initial milk expressed did not have a significantly greater amount of bacterial
      contamination than the milk collected later in the milk expression.

PMID- 1987963
TI  - Association of increased cardiothoracic ratio and intrauterine growth
      retardation.
AB  - Clinical observation suggested an association between an increased cardiothoracic
      ratio (CT) and growth retardation (IUGR) in the premature neonate. To investigate
      this hypothesis, a case-control study was performed. Study subjects included 23
      cases (IUGR) and 55 control (appropriate for gestational age [AGA]) premature
      infants with birthweights 2000 gm or less; Apgar scores greater than 5 at 5
      minutes; no congenital heart disease; no polycythemia; no toxoplasmosis, rubella,
      cytomegalovirus, or herpes infection. In random order, the first chest radiograph
      of each infant (less than 24 hours) was reviewed by a single radiologist, unaware
      of the infant's growth status. The CT ratio was computed after measuring the
      widest internal width of the bony thorax and the cardiac diameter. Mean
      birthweight (+/- 1 SD) of the IUGR infants was 1161 +/- 289 g and of AGA infants
      was 1401 +/- 401 g (p less than 0.002); the mean gestational ages (+/- 1 SD) were
      33.2 +/- 2.8 and 30.8 +/- 2.5 weeks (p less than 0.001). Mean CT for IUGR infants
      was 0.57 +/- 0.07 (+/- 1 SD) versus AGA infants, 0.51 +/- 0.04 (+/- 1 SD), p less
      than 0.001. When the infants were stratified by growth status and CT ratio, 11 of
      23 IUGR and 1 of 55 AGA infants had an increased CT ratio p less than 0.0001.
      When birthweight and gestational age were covaried, growth status remained the
      best predictor of CT, p = 0.005. There is a strong association of increased CT
      and growth retardation in premature infants with birthweights 2000 gm or less.

PMID- 1987964
TI  - Shoulder dystocia recognition: differences in neonatal risks for injury.
AB  - Shoulder dystocia (SD) is an event whose current diagnostic approach is based on
      subjective criteria alone. Since the risk for immediate neonatal morbidity is
      critically linked to recognition and appropriate management of this obstetric
      emergency, we hypothesized that infants having injuries consistent with SD are
      frequently delivered without the intrapartum identification of this condition. A
      retrospective analysis of 26,033 vaginal births from January 1979 to April 1987
      identified 162 maternal cases in which SD was diagnosed during delivery
      (incidence, 0.62%). Within this subset of patients, 24 neonates (15%) were
      identified as having either brachial plexus or fractured clavicle injuries
      associated with delivery. An additional 60 neonates were identified as having
      similar injuries immediately following delivery but without obstetric recognition
      of SD. Therefore 71% of all the injured infants were the product of deliveries
      without SD recognition. A comparison was made of maternal and neonatal variables
      for three groups (SD, uninjured; SD, injured; unrecognized SD, injured). The SD,
      injured group distinguishes itself from the other two groups by significant
      differences in the degree to which variables previously associated with SD are
      present. Conversely, both other groups are similar in all parameters except for
      accepted SD maneuvers utilized. These results support our hypothesis that SD is
      underreported in the obstetric literature and that unrecognized SD is associated
      with an increased risk of neonatal injury. Efforts to define objectively the
      threshold forces associated with neonatal injury and to develop SD teaching
      models should improve this clinical dilemma.

PMID- 1987965
TI  - Prolonged sedation associated with secobarbital in newborn infants receiving
      ventilatory support.
AB  - Newborn infants receiving ventilatory support often require sedation.
      Secobarbital is commonly used in these patients, but dosage guidelines to avoid
      prolonged sedation are not available. Seventeen infants (gestational age, 30 to
      40 weeks; postnatal age, 0 to 3 days) with hyaline membrane disease or persistent
      pulmonary hypertension on mechanical ventilation were studied. These patients
      received secobarbital, 4 to 14 mg/kg/day intravenously for 1 to 10 days to
      produce sedation. Sedation was considered prolonged if it lasted more than 24
      hours after the last dose. Nine of 17 infants experienced prolonged sedation. The
      mean daily secobarbital dose was 11.2 mg/kg/day in patients with prolonged
      sedation and 6.9 mg/kg/day in those patients without (p less than 0.05); the
      cumulative mean dose in the respective groups was 33.3 and 21.3 mg/kg (p less
      than 0.05). Four infants were sedated for 3 to 4 days after stopping
      secobarbital; the mean daily and cumulative dose was 13 mg/kg/day and 53 mg/kg in
      these patients. Duration of sedation was related to both daily and cumulative
      doses of secobarbital. Based on our results, the daily dose of secobarbital
      should not exceed 7 mg/kg/day to avoid prolonged sedation in infants. Frequent
      monitoring appears necessary to ensure efficacy with the lowest cumulative dose
      of secobarbital in newborn infants.

PMID- 1987966
TI  - Trisomy 15 associated with nonimmune hydrops.

PMID- 1987967
TI  - Spontaneous regression of a large intrathoracic fetal lesion before birth.
AB  - All fetal intrapulmonary lesions diagnosed antenatally reported in the literature
      to date have persisted as an ultrasound finding for the remainder of the
      pregnancy, although spontaneous improvement in utero has been reported recently.
      We describe a case of a large intrathoracic lesion diagnosed at 24 weeks'
      gestation by ultrasound that became indistinguishable from the rest of the lungs
      as the pregnancy approached term. Although the frequency with which this process
      occurs cannot yet be assessed, the possibility of significant spontaneous
      regression must now be considered when counseling the parents on an affected
      fetus.

PMID- 1987968
TI  - Hepatosplenomegaly as the only prenatal finding in a fetus with pyruvate kinase
      deficiency anemia.
AB  - A case of congenital pyruvate kinase deficiency manifested at antenatal
      ultrasound as isolated hepatosplenomegaly is reported and the differential
      diagnosis is discussed. An aggressive obstetric management and appropriate
      neonatal care permitted a favorable neonatal outcome.

PMID- 1987969
TI  - Fetal and uteroplacental flow velocity waveforms and placental grading.
AB  - Doppler studies were performed on umbilical, fetal internal carotid, and arcuate
      arteries within 36 to 40 weeks of gestation in 85 women (66 with healthy
      pregnancies and 18 complicated by growth retardation, and results were analyzed
      by calculating the pulsatility index. In each case the placenta was examined and
      graded sonographically. No significant correlation was found between pulsatility
      index in fetal and uteroplacental vessels and placental grading in normal
      pregnancies. This suggests that tissue changes responsible for the echogenicity
      of maturing placenta are not directly related to vascular impedance of the
      placental vascular bed.

PMID- 1987970
TI  - The effect of filtration of amniotic fluid on the growth of Chlamydia trachomatis
      and Escherichia coli.
AB  - There is increasing concern about Chlamydia trachomatis infection during
      pregnancy, because of reports of increased maternal, fetal, and neonatal risks.
      Amniotic fluid is known to possess antibacterial activity and has recently been
      shown to inhibit formation of chlamydial inclusions in McCoy cell culture. To
      further characterize the anti-chlamydial factor, we investigated the effect of
      filtering the fluid (0.45 microns pores) prior to incubation. Amniotic fluid was
      obtained from 12 women at term gestation, either by amniocentesis, or at cesarean
      section, Chlamydial inclusion formation was studied in McCoy cell cultures, and
      Escherichia coli growth was studied by a plate-count method. Filtered amniotic
      fluid had significantly less inhibitory activity against chlamydial inclusion
      formation than nonfiltered fluid did. Both filtered and nonfiltered amniotic
      fluid were equally effective in inhibiting E. coli colony growth. These data
      suggest that the chlamydial inhibitor in amniotic fluid does not pass through
      0.45 microns pores and is larger than the bacterial inhibitor that was reported
      to be a peptide of low molecular weight.

PMID- 1987971
TI  - Prenatal diagnosis and subsequent management of a fetus with a 46XY r(4)(p15-q35)
      karyotype.
AB  - Fetal ultrasound examination at 29 weeks' gestation revealed a severely
      symmetrically growth-retarded fetus with microcephaly, hypertelorism, and
      hypoplastic genitalia with a two-vessel umbilical cord. G-banding analysis on
      amniotic cell cultures revealed a 46, XY,r(4)(p15-q35) karyotype in each of the
      colonies analyzed. This prenatal diagnosis, to our knowledge the first reported,
      assisted clinical management of this pregnancy.

PMID- 1987972
TI  - Management and outcome of two pregnancies in a woman with craniodiaphyseal
      dysplasia.
AB  - Hyperostotic bone dysplasias are characterized by progressive hyperostosis and
      sclerosis of the cranium and facial bones. As a result of progressive bony
      overgrowth, intracranial pressure may increase and lead to brain and nerve
      compression, cranial nerve palsies, and an increased incidence of seizures. The
      long bones often exhibit defective modeling as well as variable degrees of
      metaphyseal and diaphyseal hyperostosis. In addition, the axial skeleton
      (including the pelvis) is often hyperostotic and sclerotic. The clinical features
      of these disorders may have relevance to the outcome of pregnancy; however, there
      are no reports on the management and pregnancy outcome of patients affected with
      hyperostotic bone disease. In this report, we describe the course of two
      pregnancies in a woman with craniodiaphyseal dysplasia (a rare craniotubular
      dysplasia). Prenatal assessment, method of delivery, choice of anesthesia, and
      neonatal management are discussed. Although this disorder is rare, the
      pathophysiologic considerations relevant to pregnancy outcome may be applicable
      to the management of pregnant women with other hyperostotic bone dysplasias.

PMID- 1987973
TI  - Role of amniotic fluid cytogenetic analysis in the evaluation of recent fetal
      death.
AB  - Chromosome abnormalities may be present in approximately 10% of cases of fetal
      death. Because of cell maceration and autolysis, the likelihood of successful
      karyotype analysis of fetal tissue varies inversely with the time between fetal
      death and delivery. In an attempt to reduce the influence of these postmortem
      changes, we obtained amniotic fluid cells for cytogenetic studies from 12 fetuses
      as soon as possible after the diagnosis of fetal death was confirmed. We also
      obtained fetal tissue for cell culture in ten of the cases immediately following
      evacuation of the uterus. Cell culture was successful in 11 of 12 amniotic fluid
      specimens and in only one of ten fetal tissue specimens (p less than 0.001).
      Since the results of cytogenetic studies are of such importance in counseling
      patients regarding recurrence risk for fetal death, we recommend that amniotic
      fluid cells be obtained for karyotype analysis at the time of diagnosis of fetal
      death rather than awaiting delivery of a potentially macerated and autolyzed
      fetus.

PMID- 1987974
TI  - Do you want an articulation plan? This is how the Colorado Model was developed.
AB  - Directors and faculty members of all the Colorado LPN, ADN, and BSN programs have
      joined together to formulate a model for statewide nursing program articulation.
      All schools will activate the model by January, 1992. The process by which this
      was accomplished is discussed in this article.

PMID- 1987976
TI  - Nursing needs minorities.
AB  - Community college and university nursing programs need to increase the number of
      nurses entering our profession with a special emphasis on those of ethnic
      minority background. To advance nursing education and the status of nursing joint
      ADN-BSN articulated nursing programs need to be developed. Many more aggressive
      and sophisticated strategies for increasing the pool of minorities nurses
      throughout the higher educational system must be employed. Only then can quality
      service to our multi-ethnic society be ensured.

PMID- 1987975
TI  - The patient with schizophrenia: helping you stay in touch with reality.
AB  - Patients with schizophrenia can be found in all clinical settings--including
      medical surgical areas. Hospitalization is an extremely stressful event for most
      patients, especially those suffering from schizophrenia. It forces them into
      unfamiliar settings and daily routines that often exaggerate their fears and
      anxieties, increasing the risk of exacerbation of psychosis. Nurses can take
      simple steps in dealing with these patients by recognizing increased feelings of
      helplessness and loss of control related to separation from significant others
      and fears of the unknown. Nurses can begin by establishing rapport as soon as
      possible and approaching the patient in a calm and reassuring manner. In
      addition, they need to identify individual needs, provide safety, and promote a
      sense of mental and physical well being.

PMID- 1987977
TI  - Ectopic pregnancy in the emergency department.

PMID- 1987978
TI  - In-flight assessment.

PMID- 1987979
TI  - 6 ways to enhance your potential.

PMID- 1987980
TI  - Current problems of nursing. A Soviet's view.

PMID- 1987981
TI  - A work-study course in an ADN program.
AB  - This article describes a nursing student practicum in which students enrolled in
      the ADN program experience the real world of work over a five week period of
      time. The student's role and the RN mentor's role are described, as well as a
      report on the findings of this unique clinical elective in a basic nursing
      program.

PMID- 1987982
TI  - Comparison of evidenced and expected ADN competencies.
AB  - These study findings indicate that nursing service administrators in the State of
      Mississippi expect strong technical level skills from the ADN. Congruency between
      nursing education and nursing service was validated. The predominance of role
      competencies outlined by nurse educators were validated as both expected and
      evidenced for the ADN in the State of Mississippi. Competencies need to be
      continually evaluated to reflect changes in the health delivery system as related
      to the ADN.

PMID- 1987983
TI  - Hypertension screenings--what's legal?

PMID- 1987984
TI  - NICU: a special clinical experience.

PMID- 1987985
TI  - Arterial hypertension. A nonpharmacologic approach.
AB  - Non-compliance for the treatment of hypertension is very high due to the
      asymptomatic nature of the disease process, the modifications of lifestyle, and
      the untoward side-effects of the medication regime. Nurses have a primary role in
      assessing, diagnosing, planning, implementing, and evaluating the effectiveness
      of an individualized nursing care plan. A master nursing care plan is included to
      assist the nurse in teaching the patient with arterial hypertension.

PMID- 1987986
TI  - Liabilities of competence.
AB  - All too often, the personal vulnerabilities of competent individuals lead them to
      take on the work of others and extend themselves beyond reasonable bounds. The
      special talents of competent individuals need to be conserved for best
      utilization. Competent persons need to carefully assess how professional and
      personal time is utilized. Rather than supporting managers who chronically
      overwork, supervisors should intervene to assist these managers in taking steps
      to protect themselves from a lifestyle that decreases career longevity and
      promotes psychological discontent.

PMID- 1987987
TI  - Reduction of endothelial microfilament bundles in the low-shear region of the
      canine aorta. Association with intimal plaque formation in hypercholesterolemia.
AB  - To interrelate in vivo wall shear stress, endothelial microfilament bundle
      formation, and atherosclerosis localization, we used a mild abdominal aortic
      stenosis in 11 beagles to produce a range of wall shear stresses above and below
      the constriction. Six of the beagles were fed standard animal chow supplemented
      with 5% cholesterol and 10% coconut oil. Wall shear stresses, endothelial
      microfilament bundles, and intimal plaque localization were assessed along the
      stenosed aorta. Shear stress was determined in vivo from the near-wall velocity
      profiles with a 20-MHz, 80-channel, multigate Doppler velocimeter. Content of the
      microfilament bundles was quantified by planimetry of transmission electron
      photomicrographs. After 6 weeks, mean shear stress was higher immediately
      upstream from the throat of the stenosis than at the proximal site (46.1 +/- 7.3
      dynes/cm2 versus 24.0 +/- 6.2 dynes/mc2, p less than 0.001) and was significantly
      lower immediately distal to the stenosis than at the proximal site (9.4 +/- 0.3
      dynes/cm2, p less than 0.01). The microfilament bundle content increased
      immediately upstream from the throat of the stenosis and decreased immediately
      distal to the stenosis compared with the proximal site in both
      normocholesterolemic and hypercholesterolemic fat-fed beagles. Intimal plaques
      formed exclusively immediately distal to the stenosis in the hypercholesterolemic
      beagles. These findings suggest that a low shear-stress environment attenuates
      endothelial microfilament bundle formation, thus leading to a predilection for
      the initiation of atherosclerosis in atherogenic conditions such as
      hypercholesterolemia.

PMID- 1987988
TI  - Interaction of low density lipoproteins with human aortic elastin.
AB  - Interaction between lipoproteins and elastin in the arterial wall may play an
      important role in atherosclerotic lipid deposition, but binding affinities and
      other characteristics of the interaction have not been determined previously.
      Elastin was isolated by hot alkali treatment of human aortic tissue. At 4 degrees
      C, radioiodinated human low density lipoprotein (LDL) bound to more than one
      class of binding sites on elastin. Sites of highest affinity had an apparent
      dissociation constant of 3.6 x 10(-8) M. Total binding at an LDL concentration of
      50 micrograms/ml ranged from 4 to 50 ng LDL protein/mg elastin. The binding was
      relatively specific, since binding was competitively inhibited by LDL and apo E
      containing high density lipoprotein (HDL) but only modestly by HDL3.
      Atherosclerotic elastin exhibited a twofold to fourfold higher capacity for
      binding LDL, but a reduced affinity. At 37 degrees C, normal elastin exhibited an
      initial rapid binding of LDL, with a slower linear phase of binding over a 15
      hour period, indicating an additional complex process at this temperature.
      Consideration of the expected LDL concentrations in the arterial intima, in
      comparison with binding affinities, suggests that LDL binding to elastin probably
      occurs in the intima and may foster atherosclerotic lipid deposition.

PMID- 1987989
TI  - Lipoprotein and apolipoprotein levels among Mexican-Americans in Starr County,
      Texas.
AB  - Mexican-Americans represent the single largest component of the US Hispanic
      population and have been shown to bear a disproportionate burden of chronic
      disease. A representative sample of 1,004 Mexican-Americans aged 15-74 years from
      Starr County, Tex., was recruited for this study. Each subject was provided a
      detailed physical evaluation that included measurement of fasting levels of
      cholesterol, triglycerides, high density lipoprotein (HDL) cholesterol and its
      subfractions (HDL2 and HDL3) alpha- and beta-lipoprotein cholesterol, and low
      density lipoprotein cholesterol. Apolipoproteins A-I, A-II, B, C-II, C-III, and E
      were determined for approximately 550 of these individuals. Age- and sex-specific
      mean levels and percentile cut points are presented. The distributions of
      lipoproteins are quite similar to those of the general population except for
      consistently higher triglycerides in males and females and lower HDL cholesterol
      levels in females. These findings are consistent with the high frequency of
      obesity. Comparative age- and sex-specific data for the apolipoproteins are not
      widely available. Where such data exist, apolipoprotein levels observed in the
      Mexican-American population tend to be similar to or lower than the comparative
      data.

PMID- 1987990
TI  - Relation of family history and reversible risk factors to coronary heart disease
      prevalence in an Afrikaner community.
AB  - In a cross-sectional study of an Afrikaner community (n = 2,722 men and n = 3,173
      women aged 25-64 years), family history of coronary heart disease (CHD) was
      associated with an adverse risk factor profile and with prevalent CHD. Men with
      myocardial infarction (MI) and a family history of CHD had higher total minus
      high density lipoprotein cholesterol (TC-HDLC) levels than men with MI but no CHD
      family history. In preliminary multiple regression analyses, family history of
      CHD appeared to exert its effect partly independently of known risk factors and
      partly dependently through age, TC minus HDLC, and HDLC. Even though their
      association with MI was weakened after entering family history into the models,
      the reversible risk factors (particularly TC minus HDLC, HDLC, and uric acid
      levels) continued to contribute to CHD. For MI in men, there was an interaction
      between family history of CHD and TC minus HDLC, to the extent that raised TC
      minus HDLC levels were adverse only in the presence of a positive CHD family
      history. The findings suggest coinheritance of high blood cholesterol and
      increased susceptibility to CHD. If confirmed in prospective studies, the
      interaction between family history and TC minus HDLC will have implications for
      cholesterol screening and management.

PMID- 1987991
TI  - Treatment with hydroxymethylglutaryl-coenzyme A reductase inhibitors in
      hypercholesterolemia induces changes in the components of the extrinsic
      coagulation system.
AB  - The present study was performed to determine the influence of pharmaceutical
      intervention on parameters of blood coagulation and fibrinolysis in
      hypercholesterolemic patients. Eighteen otherwise-healthy individuals with
      heterozygous familial hypercholesterolemia were treated with a 3-hydroxy-3
      methylglutaryl coenzyme A reductase inhibitor (simvastatin, 40 mg daily) for 12
      14 weeks followed by additional treatment with omega-3 fatty acids (equivalent to
      4 g eicosapentaenoic acid/docosahexaenoic acid daily) for 6 more weeks. With
      simvastatin treatment, the mean decreases in total cholesterol, low density
      lipoprotein (LDL) cholesterol, and apolipoprotein B (apo B) were 39%, 46%, and
      36%, respectively. Only minor changes in high density lipoprotein (HDL)
      cholesterol and apo A-1 were recorded. omega-3 fatty acids had minor additional
      effects. The most prominent effects on the blood coagulation system were the
      changes in extrinsic pathway inhibitor (EPI), which is the inhibitor of the
      factor VIIa-tissue thromboplastin complex. EPI activity decreased from a median
      of 153% to 111% (p less than 0.001) with simvastatin treatment and to 112% (p
      less than 0.001) on the combined regimen. EPI activity was significantly
      correlated with LDL cholesterol (r = 0.78), total cholesterol (r = 0.77), apo B
      (r = 0.65), and apo A-1 (r = 0.45). Multiple stepwise regression analysis showed
      that LDL cholesterol was the most important predictor of EPI activity, which
      suggests that a majority of EPI activity in plasma is associated with LDL.
      Moreover, the alteration in EPI activity was correlated closely with the
      corresponding alteration in LDL, which suggests a direct relation between a
      coagulation-inhibitor activity and a pharmaceutical lipid-related
      response.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1987992
TI  - Vastatins inhibit cholesterol ester accumulation in human monocyte-derived
      macrophages.
AB  - Human monocyte-derived macrophages were incubated for 48 hours in Medium 199 with
      1% human serum albumin, and with 100 micrograms acetyl low density lipoprotein
      (LDL) or beta-very low density lipoprotein (beta-VLDL), with or without various
      concentrations of compactin, lovastatin, simvastatin, or pravastatin. The mass of
      free (FC) and esterified (CE) cholesterol was determined, as well as the
      incorporation of [1-14C]acetate in sterols, that of [1-14C]oleate in CE, and that
      of [methyl-14C]choline in phospholipids. Moreover, we assessed the high-affinity
      association and degradation of 125I-labeled acetyl LDL. Compactin markedly
      decreased the cellular accumulation of CE induced by acetyl LDL or beta-VLDL and
      increased the content of FC. Compactin also decreased the incorporation of [1
      14C]oleate in CE (by 70-90%) in incubations with or without added lipoproteins.
      The half-maximal inhibitory concentration for this effect of compactin was 30 nM.
      Lovastatin and simvastatin were more potent, but pravastatin was about 100-fold
      less potent. Although compactin also caused a clear inhibition of cholesterol
      synthesis in the presence of acetyl LDL, the effect on CE formation did not seem
      to be related to decreased cholesterol synthesis, since this was already very low
      in the presence of acetyl LDL. Compactin did not affect the association and
      degradation of labeled acetyl LDL and also had no effect on the rate of
      cholesterol loss after preloading the cells with CE by incubation with acetyl
      LDL. However, compactin had a slight stimulatory effect on the synthesis of
      phosphatidylcholine and sphingomyelin when compactin was added to incubations in
      the presence of acetyl LDL.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1987993
TI  - The antioxidant butylated hydroxytoluene protects against atherosclerosis.
AB  - Rabbits fed a 1% cholesterol diet with or without the antioxidant butylated
      hydroxytoluene (BHT) developed typical atherosclerotic lesions. The addition of
      BHT gave higher levels of total cholesterol (+40%), triglycerides (+250%), low
      density lipoprotein (LDL), and very low density lipoprotein (VLDL) in plasma.
      Despite the lower plasma lipid levels, the degree of atherosclerosis of the
      aortic surface was considerably higher in rabbits fed cholesterol than in the
      group treated with cholesterol and BHT. The mean atherosclerotic involvement was
      18.6 +/- 4.4% in the former group and 5.9 +/- 1.7% in the latter group (p =
      0.02). In all animals, there was a high correlation between the area of the
      arterial lesion and cholesterol content (r = 0.96). Serum levels of cholesterol
      autooxidation products (7-ketocholesterol and cholesterol 5 alpha,6 alpha
      epoxide) were lower in the group of rabbits treated with BHT (p less than 0.005).
      Serum levels of vitamin E were slightly higher in the BHT group. There was no
      significant difference in the clearance of beta-VLDL between the two treatment
      groups after using either beta-VLDL from cholesterol-fed animals or beta-VLDL
      from BHT-fed animals. The results are in accord with the contention that
      oxidative modification of lipoproteins is important for the development of
      atherosclerosis and that antioxidants may have a protective effect. At present,
      however, other explanations cannot be completely excluded, for example, effects
      of antioxidants on immunologic factors or monocyte adhesion.

PMID- 1987994
TI  - Comparison of early microcirculatory and aortic changes in hypercholesterolemic
      rats.
AB  - The microcirculatory changes caused by hypercholesterolemia were studied in the
      rat cremaster muscle model by intravital microscopy and were compared with aortic
      ring segments from the same animals. Male Sprague-Dawley rats were fed either a
      normal chow diet or a chow diet supplemented with 1% cholesterol and 0.5% cholic
      acid for 3 or 5 weeks before experimentation. Three weeks of hypercholesterolemia
      produced a significantly decreased vasodilator response to serotonin in the
      arterioles. This response was also seen after 5 weeks on the hypercholesterolemia
      diet. Three weeks of hypercholesterolemia produced a significantly increased
      macromolecular leakage from postcapillary venules in response to serotonin.
      However, after 5 weeks of hypercholesterolemia, the serotonin-induced leakage was
      less than in control animals. Hypercholesterolemia for 3 weeks decreased the
      arteriolar dilation evoked by acetylcholine but did not change the arteriolar
      response to sodium nitroprusside. Contraction of the aortic rings induced by
      serotonin and aortic ring relaxation induced by sodium nitroprusside were not
      different between 3-week-control and 3-week-hypercholesterolemic animals.
      However, 3 weeks of hypercholesterolemia attenuated the aortic ring relaxation
      evoked by acetylcholine. These results suggest that hypercholesterolemia causes
      an early depression of endothelium-derived relaxing factor (EDRF)-mediated
      receptor responses in both microvessels and the aorta, whereas non-EDRF-mediated
      receptor responses are altered in the microcirculation but not in the aorta.

PMID- 1987995
TI  - Enhanced constriction of the peripheral large artery in response to acute
      induction of a low-flow state in human hypercholesterolemia.
AB  - The diameter, blood velocity, and blood flow of the brachial artery were
      evaluated with a pulsed-Doppler apparatus before and after wrist occlusion in 16
      normocholesterolemic and 27 hypercholesterolemic male subjects of similar age and
      body mass index. Before occlusion, no hemodynamic differences were observed
      between the two groups. Occlusion significantly reduced blood velocity and blood
      flow in the two groups (p less than 0.001), but such reductions were not
      different between hypercholesterolemic and normocholesterolemic groups. Occlusion
      decreased the arterial diameter in the hypercholesterolemic group only (p less
      than 0.001), and absolute diameter changes after occlusion were significantly
      different between the two groups (p less than 0.001). No correlation was found
      between the change in arterial diameter after occlusion and the baseline diameter
      before occlusion in the normocholesterolemic and hypercholesterolemic population
      overall. Absolute and percent diameter changes after occlusion were correlated
      with total cholesterol (r = -0.73, r = -0.72; p less than 0.001) and with low
      density lipoprotein (LDL) cholesterol (r = -0.68, r = -0.69; p less than 0.001)
      in the normocholesterolemic and hypercholesterolemic population overall,
      respectively. These findings indicate that the low-flow state induces a reduction
      in large-artery diameter in the hypercholesterolemic but not in the
      normocholesterolemic state and is closely related to the degree of elevation of
      blood cholesterol and of its LDL fraction.

PMID- 1987996
TI  - High density lipoproteins and coronary atherosclerosis. A strong inverse relation
      with the largest particles is confined to normotriglyceridemic patients.
AB  - The relations of high density lipoprotein (HDL) subclasses to severity and rate
      of progression of coronary atherosclerosis were investigated in 60 men who had
      survived a myocardial infarction before the age of 45 years and who had
      subsequently undergone two coronary angiographies, with an intervening time
      interval of 4-7 years between angiographies. Five HDL subclasses with different
      particle sizes were determined by gradient gel electrophoresis, and the major
      serum lipoprotein classes were separated by preparative ultracentrifugation in
      connection with the second angiography. Highly significant inverse correlations
      were found between the plasma levels of the largest HDL particles, the HDL2b
      subclass, and both disease severity as observed on the second coronary angiogram
      (r = -0.53, p less than 0.001) and progression of coronary lesions between
      angiographies (r = -0.38, p less than 0.01). Grouping the patients according to
      the presence or absence of very low density lipoprotein (VLDL) triglyceride
      elevation revealed striking differences in the relations of HDL subspecies to
      coronary atherosclerosis between normotriglyceridemic and hypertriglyceridemic
      subjects. There were strong inverse correlations between the plasma HDL2b
      concentration and both severity of lesions (r = -0.72, p less than 0.001) and
      rate of lesion progression (r = -0.58, p less than 0.01) in the
      normotriglyceridemic patients, whereas this relation was absent in subjects with
      hypertriglyceridemia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1987997
TI  - Effect of diet-induced hypercholesterolemia on proteoglycan metabolism in guinea
      pig megakaryocytes and platelets.
AB  - Proteoglycan metabolism was evaluated in megakaryocytes and platelets from guinea
      pigs fed a 1% cholesterol diet for 3 or 7 weeks. The animals were injected with a
      single dose of [35S]sulfate at the end of the feeding period, and megakaryocytes
      and platelets were isolated after 3 hours and then daily for 4 days thereafter.
      Proteoglycans were extracted from the cells of each animal and analyzed by ion
      exchange chromatography, gel filtration, and electrophoresis. The maximal
      labeling of platelets occurred 2 days after [35S]sulfate injection as compared
      with 3 days in controls. A proteoglycan that eluted at Kav 0.2 from the Sepharose
      CL-6B column appeared 1 day after labeling. Additional proteoglycans of Kav 0.15
      appeared at subsequent time points. The labeling profile for cholesterol-fed
      animals was unchanged from 2-4 days, unlike profiles from controls, which had
      exhibited a gradual increase in mean proteoglycan size. Thus, the progressive
      change in size of proteoglycans synthesized during normal megakaryocyte
      maturation was altered. The mean chain length of the proteoglycan-associated
      glycosaminoglycans from cholesterol-fed animals was increased relative to that of
      controls. In conjunction with the twofold increase in mean megakaryocyte size
      induced by cholesterol feeding in guinea pigs, the changes in proteoglycan
      synthesis suggest a state of stimulated megakaryocytopoiesis.

PMID- 1987999
TI  - Plasma triglyceride and coronary heart disease.
AB  - Although the literature on epidemiological associations between plasma
      triglyceride and CHD is not completely consistent, trends do emerge from the
      studies described here. First, the majority of observational studies demonstrate
      a significant univariate relation, although the results of case-control and cross
      sectional studies are more uniform than those from prospective study designs. In
      many but not all studies, triglyceride remains a significant predictor of CHD in
      multivariate statistical analyses after controlling for TC or LDL-C. Perhaps the
      least consistent result is that the triglyceride association does not persist in
      some analyses controlling for HDL-C, while in other studies, the association
      remains significant. Although most studies have been conducted in men, the
      studies providing data on women, normocholesterolemic subjects, and diabetic
      subjects have generally found triglyceride to be, at the very least, a univariate
      risk factor. The results of intervention trials differ considerably, but no such
      study to date has been specifically designed to evaluate triglyceride-lowering
      effects on primary prevention of CHD. Important statistical properties must be
      taken into consideration in evaluating triglyceride as a risk factor for CHD. The
      large variability of triglyceride measurements and the correlation of
      triglyceride values with other lipid measures appears to result in the
      underestimation of the association between triglyceride and disease in
      multivariate analyses. Finally, individual genetic susceptibility may play an
      important role in the relation between plasma triglyceride levels and CHD. For
      example, risk of CHD clearly varies among the well-established familial forms of
      hypertriglyceridemia. A predominance of small, dense, LDL particles (LDL subclass
      pattern B) also appears to be a genetic trait associated with both increased risk
      of MI and increases in plasma triglyceride levels.

PMID- 1987998
TI  - Effects of native and oxidized low density lipoproteins on formation and
      inactivation of endothelium-derived relaxing factor.
AB  - The influence of native (N-) and oxidized (Ox-) low density lipoproteins (LDLs)
      on endothelium-dependent vasomotion is still controversial. We investigated the
      short-term effects of N-LDL and Ox-LDL on the formation of endothelium-derived
      relaxing factor (EDRF) in native and cultured endothelial cells and on its
      inactivation after release from the cells. N-LDL was isolated from fresh human
      plasma via sequential ultracentrifugation and oxidized by incubation with Cu2+.
      EDRF released from cultured endothelial cells was inactivated by both N-LDL and
      Ox-LDL (1 mg/ml) as detected in a bioassay system. N-LDL reduced the EDRF
      mediated vasodilations of the detector segments by 38.5 +/- 5.3%, and Ox-LDL, by
      55.5 +/- 4.6%. The effects of lipoproteins on EDRF formation were studied in
      cultured endothelial cells preincubated with either N-LDL or Ox-LDL (1 mg/ml for
      1 hour) and stimulated for EDRF release with bradykinin after washout of the
      lipoproteins. EDRF was assessed by measuring its stimulatory effect on the
      activity of a purified, soluble guanylate cyclase. Both N-LDL and Ox-LDL did not
      reduce the bradykinin-induced EDRF formation. Consistent with this finding,
      acetylcholine-induced, EDRF-mediated dilations of intact rabbit femoral artery
      segments were not impaired by luminal exposure to N-LDL or Ox-LDL (1 mg/ml for 1
      hour). However, these relaxations were significantly reduced by preincubation of
      aortic ring preparations with the same concentrations of the same charges of N
      LDL and Ox-LDL. In conclusion, neither N-LDL nor Ox-LDL acutely impairs the
      formation of EDRF but does inactivate EDRF after its release from endothelial
      cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1988000
TI  - Steenbock symposium on molecular biology of atherosclerosis.

PMID- 1988001
TI  - Effects of estrogen and progesterone on plasma lipoproteins and experimental
      atherosclerosis in the baboon (Papio sp.).
AB  - We determined the effect of estrogen and progesterone on plasma cholesterol and
      lipoprotein cholesterol concentrations and on arterial lesions in 24
      ovariectomized and hysterectomized baboons fed a high-cholesterol/high-saturated
      fat diet. These baboons were divided into four groups: untreated control (C);
      estrogen, 100 micrograms/kg/week injected i.m. (E); progesterone, 3 mg/kg/day
      (P); and estrogen plus progesterone (E + P). The treatment regimen continued for
      18 months. Cholesterol levels in plasma and lipoproteins were measured before
      hormone treatment and at 3, 10, and 18 months of treatment. Postheparin plasma
      lipoprotein lipase (LPL) activity was also measured during the treatment. After
      18 months of hormone treatment, baboons were necropsied and arterial lesions were
      measured. Hormone treatment significantly influenced plasma cholesterol (P
      greater than C greater than [E + P] greater than E) and very low density
      lipoprotein plus low density lipoprotein (VLDL + LDL) cholesterol (P greater than
      C greater than [E + P] greater than E), with very little effect on high density
      lipoprotein (HDL) cholesterol concentration. The E + P group had a significantly
      higher HDL cholesterol concentration than did the P group. The (VLDL + LDL)/HDL
      cholesterol ratios in the E and E + P groups were significantly lower than those
      in the P and C groups. LPL activities were significantly lower in the E group
      compared with those in the E + P and P groups. Hormone treatment significantly
      influenced lesions in four (innominate, carotid, iliac, and abdominal aorta) of
      seven arteries. The P group had the most fatty streaks, and the E + P group had
      the least.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1988002
TI  - Dose response of dietary fish oil supplementations on platelet adhesion.
AB  - A dose-response study of dietary fish oil supplementation on platelet adhesion
      was performed in three groups of five normal individuals each. Fish oil
      equivalent to 3, 6, or 9 g eicosapentaenoic acid (EPA)/day was administered for 3
      weeks, and platelet adhesion was evaluated under high and low shear rate
      conditions in a laminar flow chamber before, during, and after termination of
      fish oil administration. Platelet adhesion to collagen I and fibrinogen, the two
      test surfaces in this study, was greatly reduced in response to fish oil. The
      inhibitory effect was similar whether platelet adhesion was evaluated at high or
      low shear rates. Maximal inhibitory activity was noted at 6 g EPA/day. A delayed
      onset and prolonged washout period characterized the response. The washout period
      of the fish oil effect was inversely related to the level of dietary
      supplementation. Measurement of total fatty acid distribution in platelets showed
      a dose-related increase in n-3 polyunsaturated fatty acids. From these studies,
      it is concluded that fish oil is an effective inhibitor of platelet adhesion,
      which reaches its maximum effect at approximately 6 g EPA/day.

PMID- 1988003
TI  - Effects of n-3 and n-6 fatty acid-enriched diets on plasma lipoproteins and
      apolipoproteins in heterozygous familial hypercholesterolemia.
AB  - Polyunsaturated fatty acids in vegetable (n-6) and marine (n-3) oils have been
      shown to reduce cholesterol levels in normolipidemic individuals. However, there
      is relatively little information available on the lipoprotein responses to
      dietary n-6 and n-3 fatty acids in individuals with genetic forms of
      hyperlipidemia at risk for premature cardiovascular disease. We studied five
      subjects with heterozygous familial hypercholesterolemia (FH), as well as five
      normal controls, on three rigidly controlled diets differing primarily in their
      fatty acid composition. FH subjects reduced their total plasma cholesterol by 34%
      during the n-3 diet and by 26% with the n-6 diet (both p less than 0.001) when
      compared with values while on a butter diet. In addition, low density lipoprotein
      (LDL) cholesterol fell 31% and 29% (both p less than 0.001), and apolipoprotein B
      (apo B) levels dropped 28% and 27% (both p less than 0.01) during the n-3 and n-6
      diets, respectively. A significant reduction of total and LDL cholesterol as well
      as of apo B was also noted in normal controls during n-3 and n-6 diets. Total
      plasma triglyceride and high density lipoprotein cholesterol fell significantly
      during n-3 diets in normal and FH subjects. Thus, FH and normal subjects respond
      in a similar fashion to diets low in saturated fatty acids and rich in n-3 and n
      6, with decreased LDL cholesterol and apo B concentrations.

PMID- 1988004
TI  - Net mass transfer of cholesteryl esters from low density lipoproteins to high
      density lipoproteins in plasma from normolipidemic subjects.
AB  - Net mass transfer of lipids was measured in plasma from fasted, normolipidemic
      subjects. The plasma was incubated, and lipoproteins were subsequently separated
      by polyanion precipitation or density gradient ultracentrifugation. Total
      cholesterol, unesterified cholesterol, and triglycerides were measured in the
      isolated lipoprotein fractions. The rate of cholesterol esterification was
      measured simultaneously. All plasma samples showed an increase in high density
      lipoprotein (HDL) cholesteryl esters during 1-hour incubations. In most cases,
      this increase was higher than the cholesteryl ester formation in total plasma due
      to cholesterol esterification. Therefore, we concluded that a net mass transfer
      of cholesteryl esters occurred from the very low plus low density lipoprotein
      (VLDL + LDL) fractions to HDL in plasma from most of the subjects studied.
      Transfer of triglycerides occurred from VLDL + LDL to HDL in plasma from all
      subjects. The cholesteryl ester transfer (measured after 1 hour) is not related
      to the activity of cholesteryl ester transfer protein. Inhibition of cholesterol
      esterification did not change the direction of cholesteryl ester or triglyceride
      transfer. Ultracentrifugal separation of plasma lipoproteins revealed that both
      HDL and VLDL are acceptors of cholesteryl esters and that VLDL donates
      triglycerides to both LDL and HDL. Removal of VLDL from plasma by
      ultracentrifugation did not affect the cholesteryl ester transfer from LDL to
      HDL. We conclude that LDL may act as a donor of cholesteryl esters during
      incubation of normolipidemic plasma.

PMID- 1988005
TI  - Cholesterol esterification rates in very low density lipoprotein- and low density
      lipoprotein-depleted plasma. Relation to high density lipoprotein subspecies,
      sex, hyperlipidemia, and coronary artery disease.
AB  - The fractional rate of cholesterol esterification in very low density lipoprotein
      and low density lipoprotein-depleted plasma (FERHDL) was studied in
      normolipidemic subjects and in individuals with hyperlipidemia and proven
      coronary artery disease (CAD). The FERHDL was significantly higher than the FER
      in whole plasma and was significantly higher in normal men than in normal women.
      In addition, men and women with primary hyperlipidemia had significantly higher
      FERHDL values relative to their sex-matched controls. The most significant
      increases in FERHDL values, however, were observed in individuals with CAD. In
      all patient groups, FERHDL was positively correlated with plasma triglyceride
      concentration. In addition, FERHDL was negatively related to plasma high density
      lipoprotein (HDL) cholesterol concentration in all groups except in men with CAD
      and in normolipidemic women. The gradient gel electrophoretic pattern of HDL from
      individuals with either low or high FERHDL values indicated an inverse relation
      between this activity and the relative amount of HDL2b particles. FERHDL likely
      reflects the metabolic properties of the heterogeneous population of HDL
      particles in the plasma and may be a function of the relative content of larger
      and smaller HDL particles. It appears to be a sensitive and reliable functional
      measure of the particle size distribution in the HDL pool and one of potential
      clinical value in the assessment of risk for CAD.

PMID- 1988006
TI  - Detection of two species of low density lipoprotein particles in cholesteryl
      ester transfer protein deficiency.
AB  - By equilibrium density gradient ultracentrifugation, we analyzed the chemical
      composition and particle size of low density lipoproteins (LDLs) in 16
      subfractions separated from the LDL fractions (1.019 less than d less than 1.063
      g/ml) of two hyperalphalipoproteinemic patients who had a deficiency of
      cholesteryl ester transfer protein (CETP). The LDLs of these patients comprised a
      group of heterogeneous lipoprotein particles distributed almost equally in a wide
      density range from d = 1.025 g/ml to d = 1.053 g/ml, whereas LDLs from normal
      controls were a homogeneous group of lipoprotein particles distributed in a
      narrow density range from d = 1.030 g/ml to d = 1.046 g/ml. The LDL in each
      subfraction derived from the patients' plasma samples was poor in cholesteryl
      ester and rich in triglycerides and apolipoproteins. Each subfraction of normal
      control LDL contained only one species of homogeneous LDL particles, which
      progressively decreased in size with an increase in the density of the fraction.
      In contrast, each subfraction of patient LDL contained two species of LDL
      particles: smaller LDLs existed, in addition to those that were found to be
      identical to the normal control LDL particles observed in the corresponding
      subfractions. The intermediate density lipoproteins of the two patients were also
      composed of two species of lipoproteins. From these results, we speculate that
      two metabolic pathways may exist in the LDL formation process. In this process,
      the transfer of cholesteryl ester from high density lipoproteins by CETP may
      convert the smaller lipoprotein particles to the larger ones, forming the
      homogeneous LDL species.

PMID- 1988007
TI  - High fasting plasma insulin is an indicator of coronary heart disease in non
      insulin-dependent diabetic patients and nondiabetic subjects.
AB  - The association between fasting plasma insulin level and coronary heart disease
      (CHD) was studied in 909 non-insulin-dependent diabetic (NIDDM) patients, aged 45
      64 years, and in 1,373 nondiabetic control subjects. Both diabetic and
      nondiabetic subjects with various manifestations of CHD had higher plasma insulin
      levels than did subjects free of CHD. By plasma insulin quintiles formed
      according to values in nondiabetic subjects, the age-adjusted prevalence of CHD
      defined by symptoms and/or electrocardiographic changes in diabetic men was 48.2%
      in quintiles I + II (lowest), 54.8% in quintiles III + IV, and 65.7% in quintile
      V (highest) (p = 0.006). The respective prevalences in diabetic women were 53.5%,
      59.1%, and 73.3% (p = 0.004); in nondiabetic men, 28.1%, 33.7%, and 43.3%,
      respectively (p = 0.016); and in nondiabetic women, 28.1%, 34.9%, and 44.3%,
      respectively (p = 0.007). An essentially similar association was observed between
      plasma insulin level and definite or possible myocardial infarction (MI). In
      diabetic subjects, a positive association between plasma insulin level and CHD
      manifestations was also found when insulin strata were formed using quintile
      cutoff points determined separately from diabetic subjects. The association
      between plasma insulin level and the prevalence of CHD or MI disappeared or was
      weaker, especially in men, when adjustment was made for body mass index,
      hypertension, and triglyceride or high density lipoprotein (HDL) cholesterol
      level. The association between high plasma insulin level and CHD was significant
      in diabetic subjects with a body mass index greater than 27 kg/m2 but not in
      those diabetics with a body mass index less than or equal to 27 kg/m2. A
      significant clustering of hypertension, high triglyceride values, and low HDL
      cholesterol levels was observed in diabetic subjects in the highest insulin
      quintiles. The results suggest that hyperinsulinemia is an indicator of CHD in
      both NIDDM patients and nondiabetic subjects. Hyperinsulinemia may be directly
      atherogenic, but it is more probable that hyperinsulinemia reflects insulin
      resistance, which may be a factor enhancing atherogenesis by causing adverse
      changes in many CHD risk factors.

PMID- 1988008
TI  - Effects of injury and insulin on lipid synthesis from glucose by the rat thoracic
      aorta.
AB  - Chronic hyperinsulinemia is suspected of enhancing the development of arterial
      diseases. However, direct metabolic effects of insulin on the inner arterial wall
      are poorly documented. To assess the possible influence of variations in smooth
      muscle phenotype, we measured lipogenesis from glucose by rat thoracic aortas
      that had been injured with a balloon catheter. Aortas were exposed to insulin
      during either a 1-hour incubation or a 9-minute perfusion. Injury transiently
      stimulated lipogenesis by the intima-media (by 111% and 225% on the second day
      after injury in two separate experiments). However, insulin added either to the
      incubation medium or to the perfusion medium, even at a very high concentration
      (10(5) microunits/ml), did not modify lipogenesis by the intima-media as long as
      14 days after injury. In contrast, two days after injury, the adventitia
      responded to insulin in a dose-dependent manner. We conclude that: 1) Injury
      transiently stimulates lipogenesis from glucose by the intima-media. 2) The
      change in smooth muscle cell phenotype, from contractile to synthetic, does not
      influence the metabolic sensitivity of the intima-media to insulin. 3) Our
      results do not substantiate the view that insulin contributes to the development
      of cardiovascular diseases through a direct lipogenic effect on arterial smooth
      muscle cells.

PMID- 1988009
TI  - Transcriptional regulation of the heat-shock response: a plant perspective.

PMID- 1988010
TI  - Inhibition of HIV protease activity by heterodimer formation.
AB  - The dimeric nature of the HIV protease has been exploited to devise a novel mode
      of inhibiting the enzyme. The use of defective monomers or nonidentical subunits
      to exchange with wild-type homodimers produces catalytically defective
      heterodimers. Incubation of the HIV1 or HIV2 protease with a 4-fold molar excess
      of an inactive mutant of HIV1 leads to 80 and 95% inhibition of enzyme activity,
      respectively. Incubating HIV1 and HIV2 proteases at a 1:5 ratio results in a 50%
      reduction of activity of the mixed enzymes. The HIV1/HIV2 heterodimer was
      identified by ion-exchange HPLC. The heterodimer may display a disordered dimer
      interface, thereby affecting the catalytic potential of the enzyme. This
      mechanism of inactivation is an example of a dominant negative mutation that can
      obliterate the activity of a naturally occurring multisubunit enzyme.
      Furthermore, it provides an alternative to active-site-directed inhibitors for
      the development of antiviral agents that target the dimeric interface of the HIV
      protease.

PMID- 1988011
TI  - Lactoperoxidase-catalyzed oxidation of thiocyanate by hydrogen peroxide: 15N
      nuclear magnetic resonance and optical spectral studies.
AB  - To establish the agent(s) responsible for the activity of the lactoperoxidase
      (LPO)/SCN-/H2O2 system, the oxidation of thiocyanate with hydrogen peroxide,
      catalyzed by lactoperoxidase, has been studied by 15N NMR and optical
      spectroscopy at different concentrations of thiocyanate and hydrogen peroxide and
      at different pHs. The formation of hypothiocyanite ion (OSCN-) as one of the
      oxidation products correlated well with the activity of the LPO/SCN-/H2O2 system
      and was maximum when the concentrations of the H2O2 and SCN- were nearly the same
      and the pH was less than 6.0. At [H2O2]/[SCN-] = 1, OSCN- decomposed very slowly
      back to thiocyanate. When the ratio [H2O2]/[SCN-] was above 2, formation of CN-
      was observed, which was confirmed by 15N NMR and also by changes in the optical
      spectrum of LPO. The oxidation of thiocyanate by H2O2 in the presence of LPO does
      not take place at pH greater than 8.0. Since thiocyanate does not bind to LPO
      above this pH, the binding of thiocyanate to LPO is considered to be prerequisite
      for the oxidation of thiocyanate. Maximum inhibition of oxygen uptake by
      Streptococcus cremoris 972 bacteria was observed when hydrogen peroxide and
      thiocyanate were present in equimolar amounts and the pH was below 6.0.

PMID- 1988012
TI  - Four-dimensional 13C/13C-edited nuclear Overhauser enhancement spectroscopy of a
      protein in solution: application to interleukin 1 beta.
AB  - A four-dimensional 13C/13C-edited NOESY experiment is described which
      dramatically improves the resolution of protein NMR spectra and enables the
      straightforward assignment of nuclear Overhauser effects involving aliphatic
      and/or aromatic protons in larger proteins. The experiment is demonstrated for
      uniformly (greater than 95%) 13C-labeled interleukin 1 beta, a protein of 153
      residues and 17.4 kDa, which plays a key role in the immune response. NOEs
      between aliphatic and/or aromatic protons are first spread out into a third
      dimension by the 13C chemical shift of the carbon atom attached to the
      originating proton and subsequently into a fourth dimension by the 13C chemical
      shift of the carbon atom attached to the destination proton. Thus, each NOE cross
      peak is labeled by four chemical shifts. By this means, ambiguities in the
      assignment of NOEs that arise from chemical shift overlap and degeneracy are
      completely removed. Further, NOEs between protons with the same chemical shifts
      can readily be detected providing their attached carbon atoms have different 13C
      chemical shifts. The design of the pulse sequence requires special care to
      minimize the level of artifacts arising from undesired coherence transfer
      pathways, and in particular those associated with "diagonal" peaks which
      correspond to magnetization that has not been transferred from one proton to
      another.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1988013
TI  - Resonance Raman spectroscopy of methylamine dehydrogenase from bacterium W3A1.
AB  - Resonance Raman spectroscopy has been used to probe the structure of the
      covalently bound quinone cofactor in methylamine dehydrogenase from the bacterium
      W3A1. Spectra were obtained on the phenylhydrazine and 2-pyridylhydrazine
      derivatives of the native enzyme, on the quinone-containing subunit labeled with
      phenylhydrazine, and on an active-site peptide also labeled with phenylhydrazine.
      Comparisons of these spectra to the corresponding spectra of copper-containing
      amine oxidase derivatives indicate that the quinones in these two classes of
      quinoproteins are not identical. The resonance Raman spectra of the native enzyme
      and small subunit have also been measured. 16O/18O exchange permitted the
      carbonyl modes of the quinone to be identified in the resonance Raman spectrum of
      oxidized methylamine dehydrogenase: a band at 1614 cm-1, together with a shoulder
      at 1630 cm-1, are assigned as modes containing substantial C = O stretching
      character. D2O/H2O exchange has pronounced effects on the resonance Raman
      spectrum of the oxidized enzyme, suggesting that the quinone may have numerous
      hydrogen bonds to the protein or that it is unusually sensitive to the local
      environment. Resonance Raman spectra of the isolated small subunit, and its
      phenylhydrazine derivative, are considerably different from the corresponding
      spectra of the intact protein. An attractive explanation for these observations
      is that the quinone cofactor in methylamine dehydrogenase from W3A1 is located at
      the interface between the large and small subunits, as found for the enzyme from
      Thiobacillus versutus [Vellieux, F. M. D., Huitema, F., Groendijk, H., Kalk, K.
      H., Frank, J. Jzn., Jongejan, J. A., & Duine, J. A. (1989) EMBO J. 8, 2171
      2178].(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1988014
TI  - Comparison of various molecular forms of bovine trypsin: correlation of infrared
      spectra with X-ray crystal structures.
AB  - Fourier-transform infrared spectroscopy is a valuable method for the study of
      protein conformation in solution primarily because of the sensitivity to
      conformation of the amide I band (1700-1620 cm-1) which arises from the backbone
      C = O stretching vibration. Combined with resolution-enhancement techniques such
      as derivative spectroscopy and self-deconvolution, plus the application of
      iterative curve-fitting techniques, this method provides a wealth of information
      concerning protein secondary structure. Further extraction of conformational
      information from the amide I band is dependent upon discerning the correlations
      between specific conformational types and component bands in the amide I region.
      In this paper, we report spectra-structure correlations derived from
      conformational perturbations in bovine trypsin which arise from autolytic
      processing, zymogen activation, and active-site inhibition. IR spectra were
      collected for the single-chain (beta-trypsin) and once-cleaved, double-chain
      (alpha-trypsin) forms as well as at various times during the course of autolysis
      and also for zymogen, trypsinogen, and beta-trypsin inhibited with diisopropyl
      fluorophosphate. Spectral differences among the various molecular forms were
      interpreted in light of previous biochemical studies of autolysis and the known
      three-dimensional structures of the zymogen, the active enzyme, and the DIP
      inhibited form. Our spectroscopic results from these proteins in D2O imply that
      certain loop structures may absorb in the region of 1655 cm-1. Previously, amide
      I' infrared bands near 1655 cm-1 have been interpreted as arising solely from
      alpha-helices. These new data suggest caution in interpreting this band. We have
      also proposed that regions of protein molecules which are known from
      crystallographic experiments to be disordered absorb in the 1645 cm-1 region and
      that type II beta-turns absorb in the region of 1672-1685 cm-1. Our results also
      corroborate assignment of the low-frequency component of extended strands to
      bands below 1636 cm-1. Additionally, the results of multiple measurements have
      allowed us to estimate the variability present in component band areas calculated
      by curve fitting the resolution-enhanced IR spectra. We estimate that this
      approach to data analysis and interpretation is sensitive to changes of 0.01 unit
      or less in the relative integrated intensities of component bands in spectra
      whose peaks are well resolved.

PMID- 1988015
TI  - Circular dichroism study on the conformational stability of the dimerization
      domain of transcription factor LFB1.
AB  - LFB1, a dimeric DNA binding protein, is a major determinant of hepatocyte
      specific transcription. The thermal and chemical equilibrium unfolding of a 32
      residue alpha-helical peptide comprising its dimerization domain (B1-Dim) was
      monitored by circular dichroism spectroscopy. The conformational stability of
      this peptide is shown to be concentration dependent, and the unfolding reaction
      is described as a two-state transition between folded dimers and unfolded
      monomers. The thermodynamic parameters associated with the unfolding reaction
      were determined under the two-state assumption by the van't Hoff procedure. The
      enthalpy of unfolding increases linearly with temperature, and the corresponding
      value of delta Cp, the difference in heat capacity between the unfolded and the
      folded forms of the peptide, is estimated to be ca. 0.7 kcal mol-1 K-1. The
      dimeric folded structure of the peptide is stabilized, at 25 degrees C, by a
      delta G of about 11.5 kcal mol-1, which is equivalent to a dimerization constant
      greater than 10(8) mol-1. These results indicate that the dimerization domain of
      LFB1 can fold and dimerize independently of the rest of the protein, with a
      thermodynamic stability comparable to that of a small globular protein.

PMID- 1988016
TI  - 1H resonance assignment and secondary structure determination of the dimerization
      domain of transcription factor LFB1.
AB  - We have started the structure determination of the dimerization domain of LFB1 in
      solution by nuclear magnetic resonance in order to elucidate the way that the
      LFB1 protein dimerizes and then interacts with DNA. A 32 amino acid peptide was
      synthesized, and full assignment of the NMR resonances in acidic solution was
      achieved. The secondary structure determination is presented here. Three
      structurally distinct regions can be distinguished. The N-terminal region from
      residues 1 to 6 is extended. Two helical regions span from residues 7 to 18 and
      from 23 to 32. The absence of dipolar effects involving residues more than four
      positions apart in the sequence excludes the possibilities both of a four-helix
      bundle formed by two hairpins and of an antiparallel dimer; the domain must
      therefore be arranged as a parallel dimer formed by kinked monomers. This
      structural solution presents important differences from the leucine zipper-type
      structure observed in other transcriptional activators. Although further studies
      are still necessary to determine the 3D structure of the peptide, we can exclude
      the possibility of a coiled-coil structure.

PMID- 1988017
TI  - Electrostatic contributions to the binding of Ca2+ in calbindin D9k.
AB  - A set of accurate experimental data is provided for Ca2+ ion binding to calbindin
      D9k, a protein in the calmodulin superfamily of intracellular regulatory
      proteins. The study comprises both the role of protein surface charges and the
      effects of added electrolyte. The two macroscopic Ca2(+)-binding constants K1 and
      K2 are determined for the wild-type and eight mutant calbindins in 0, 0.05, 0.10,
      and 0.15 M KCl from titrations in the presence of Quin 2 or 5,5'-Br2BAPTA. The
      mutations involve replacement of surface carboxylates (of Glu17, Asp19, Glu26,
      and Glu60) with the corresponding amides. It is found that K1K2 may decrease by a
      factor of up to 2.5 x 10(5) (triple mutant in 0.15 M KCl as compared to the wild
      type protein in 0 M KCl). Ca2(+)-binding constants of the individual Ca2+ sites
      (microscopic binding constants) have also been determined. The positive
      cooperativity of Ca2+ binding, previously observed at low salt concentration
      [Linse et al. (1987) Biochemistry 26, 6723-6735], is also present at
      physiological ionic strength and amounts to 5 kJ.mol-1 at 0.15 M KCl. The
      electrolyte concentration and some of the mutations are found to affect the
      cooperativity. 39K NMR studies show that K+ binds weakly to calbindin. Two
      dimensional 1H NMR studies show, however, that potassium binding does not change
      the protein conformation, and the large effect of KCl on the Ca2+ affinity is
      thus of unspecific nature. Two-dimensional 1H NMR has also been used to assess
      the structural consequences of the mutations through assignments of the backbone
      NH and C alpha H resonances of six mutants.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1988018
TI  - Polymerization site in the beta chain of fibrin: mapping of the B beta 1-55
      sequence.
AB  - The formation of a fibrin clot occurs through binding of putative complementary
      sites, called fibrin polymerization sites, located in the NH2- and COOH-terminal
      domains of fibrin monomer molecules. In this study, we have investigated the
      structure of the NH2-terminal fibrin polymerization site by using fibrinogen
      derived peptides and fragments. Fibrinogen was digested with Crotalus atrox
      protease III, to two major molecular species: a Mr 325,000 derivative (Fg325) and
      a peptide of Mr 5000. The peptide and its thrombin-cleavage product were purified
      by ion-exchange and reverse-phase HPLC; the authenticity of the B beta 1-42 and
      beta 15-42 peptides, respectively, was confirmed by amino acid sequencing. Since
      Fg325 had decreased thrombin coagulability, we addressed the question of whether
      the peptide B beta 1-42 contained a fibrin polymerization site. In order to
      identify and map the site, the peptides B beta 1-42 and beta 15-42 were tested
      for their ability to inhibit fibrin monomer polymerization. In addition the
      following peptides prepared by chemical synthesis were also tested: beta 15-18,
      beta 15-26, beta 24-42, beta 40-54, beta 50-55, and alpha 17-19-Pro. While B beta
      1-42 had no inhibitory activity, the peptide devoid of fibrinopeptide B, beta 15
      42, was a strong inhibitor. The peptides beta 15-18, beta 15-26, and beta 15-42
      decreased the rate of fibrin polymerization by 50% at a molar excess of the
      peptide to fibrin monomer of 500, 430, and 50, respectively. The peptides beta 24
      42, beta 40-54, and beta 50-55 were inactive.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1988019
TI  - Identification of bull protamine disulfides.
AB  - We have identified the disulfide cross-links in bull protamine by titrating
      intact bull sperm with dithiothreitol (DTT) and following the modification of
      each cysteine residue with tritiated iodoacetate. The derivatization of each
      cysteine was monitored by a combination of HPLC, peptide mapping, and protein
      sequencing. Analyses of total free sulfhydryls show that all seven of the bull
      protamine cysteines are cross-linked as disulfides in mature sperm. The first
      disulfide is reduced at a DTT:protamine cysteine (DTT:Cys) ratio of 0.3 and the
      last at a ratio of 2.0. Intra- and intermolecular disulfides were identified by
      correlating the reduction of specific disulfides with the dissociation of
      protamine from DNA in partially reduced sperm and sperm treated with N,N'
      ethylenedimaleimide, a bifunctional disulfide cross-linking agent. Three
      intermolecular and two intramolecular disulfides were identified. The results of
      these experiments demonstrate that the amino- and carboxy-terminal ends of the
      bull protamine molecule are folded inward toward the center of the molecule and
      are locked in place, each by a single intramolecular disulfide bridge. Three
      intermolecular disulfides cross-link neighboring protamine molecules around the
      DNA helix in such a manner that the protamines cannot be dissociated from DNA
      without first reducing the interprotamine disulfides.

PMID- 1988020
TI  - Preparation and characterization of N-(1-pyrenyl)iodoacetamide-labeled
      Escherichia coli RNA polymerase.
AB  - N-(1-Pyrenyl)iodoacetamide has been used to introduce fluorescent probes into
      Escherichia coli RNA polymerase. After an incubation time of 15 min,
      approximately 2 pyrene equiv was introduced per enzyme molecule. There was no
      further increase in modification after more extended periods of incubation.
      Neither calf thymus DNA nor nucleotides protected the holoenzyme from
      modification. Thus, the sites of modification do not appear to involve the
      binding sites for polynucleotides or the ribonucleoside triphosphates. From the
      isolation and analysis of the individual subunits, it was found that sigma
      contained approximately 1 pyrene equiv, beta contained 0.6, beta' contained 0.6,
      and alpha less than 0.1. Spectral and Stern-Volmer analyses indicate that the
      covalently attached pyrene molecules are in comparable apolar microenvironments.
      On the basis of CD analyses, the introduction of pyrene molecules into RNA
      polymerase alters its secondary structure. This alteration in secondary structure
      manifests itself by a reduction in overall enzymatic activity. Transcript
      analysis of the products obtained by using a linearized plasmid containing the A1
      promoter and the Te terminator of bacteriophage T7 indicates that the pyrenyl
      derivative is capable of producing full-length transcripts and that it has an
      efficiency of chain termination comparable to the native enzyme. Analysis of tau
      plots for the interaction of the pyrenyl derivative and the native enzyme,
      respectively, with the A1 promoter yielded comparable values for the
      isomerization constant in the conversion of the closed complex to an open one.
      Comparable values were also obtained for the association constant. The rate of
      chain elongation for the pyrenyl derivative, however, is approximately 54% of
      that observed for the native enzyme. Thus, the decrease in overall
      transcriptional activity observed with the pyrenyl derivative is not due to a
      decrease in the efficiency of initiation or premature termination, but rather to
      a decrease in the rate of chain elongation.

PMID- 1988021
TI  - Ganglioside GM1 and asialo-GM1 at low concentration are preferentially
      incorporated into the gel phase in two-component, two-phase phosphatidylcholine
      bilayers.
AB  - Multilamellar liposomes composed of 1:1 dielaidoylphosphatidylcholine:
      dipalmitoylphosphatidylcholine at 20 degrees C contain laterally separated gel
      and liquid-crystalline phases that can be identified by electron microscopy in
      freeze-etch replicas on the basis of their distinctive morphology. Visualization
      of marker proteins that specifically bind to glycosphingolipids included in these
      liposomes has revealed that, at 1 mol % or less, the ganglioside GM1 and the
      neutral asialo-GM1 derived from it are localized within the gel-phase regions
      exclusively. Increasing the mole fraction of the glycosphingolipids results in
      the appearance of marker in the fluid-phase regions. Another neutral
      glycosphingolipid, Forssman, does not display a phase preference and is found in
      both phases at a low mole percent. The phase preference of these three
      glycosphingolipids depends primarily upon interactions between the hydrophobic
      moieties of these molecules and the matrix phosphatidylcholines.

PMID- 1988022
TI  - Nonspecific interaction of Escherichia coli pyrenyl RNA polymerase holoenzyme
      with synthetic polynucleotides as monitored by fluorescence spectroscopy.
AB  - A derivative of RNA polymerase containing approximately 2 pyrene equiv per enzyme
      molecule has been used to study the interaction of RNA polymerase with poly[d(A
      T)].poly[d(A-T)] and poly[d-(G-C)].poly[d(G-C)]. As monitored by fluorescence
      spectroscopy, pyrenyl RNA polymerase displays a unique set of conformational
      changes with each synthetic polynucleotide as a function of temperature. An
      increase in the fluorescence intensity was observed for both polynucleotides at 5
      degrees C. A decrease was observed in the case of poly[d(A-T)].poly[d(A-T)] at 25
      and 37 degrees C, whereas no discernible perturbation was observed in the case of
      poly[d(G-C)].poly[d(G-C)]. Different salt dependencies were observed for the
      interaction of pyrenyl RNA polymerase with these polynucleotides at 5 and 25
      degrees C. Further characterization of these interactions as well as correlation
      of the observed fluorescence changes to the corresponding open and closed
      complexes was carried out with heparin. The interaction between pyrenyl RNA
      polymerase and poly[d-(A-T)].poly[d(A-T)] at 25 degrees C was quantified by using
      two different methods.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1988023
TI  - Transcription by eucaryotic and procaryotic RNA polymerases of DNA modified at a
      d(GG) or a d(AG) site by the antitumor drug cis-diamminedichloroplatinum(II).
AB  - We have investigated whether DNA modified at a d(GG) or a d(AG) site by the
      chemotherapeutic drug cis-diamminedichloroplatinum(II) (cis-DDP) can be used as
      template by wheat germ RNA polymerase II. The templates used in the present study
      were obtained by ligation of double-helical oligodeoxyribonucleotides, containing
      18 pyrimidine bases and 2 central dG, or dA and dG, bases on one strand and 18
      purine bases and 2 central dC, or dT and dC, bases on the complementary strand.
      Therefore, the cis-DDP adducts are only present on one strand of each of the two
      templates and are regularly spaced by 18 pyrimidine bases. These constructs
      allowed us to investigate the effect of cis-DDP on transcription of the
      platinated strand and of the complementary unplatinated sequence. Transcription
      experiments were carried out in the presence of dinucleotide primers and either a
      single triphosphate substrate (abortive elongation) or the full set of
      triphosphate substrates dictated by the template sequence (productive
      elongation). The results show that the eucaryotic RNA polymerase can catalyze
      dinucleotide-primed reactions on platinated DNA. However, the eucaryotic enzyme
      behaved very differently depending on which strand was transcribed. Thus,
      transcription elongation was completely blocked on the strand carrying the metal
      complex, whereas transcription elongation was not blocked on the complementary
      template strand. However, on this latter strand and with the platinated polymers,
      productive elongation was slightly inhibited. Furthermore, abortive elongation
      leading to dinucleotide-primed trinucleotide formation was enhanced on the
      template strand complementary to that carrying the cis-DDP adducts.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1988025
TI  - Empirical estimation of the gel to liquid-crystalline phase transition
      temperatures for fully hydrated saturated phosphatidylcholines.
AB  - Phospholipids are a major component of biological membranes. In excess water,
      phospholipids may self-assemble into fully hydrated lamellae which, upon heating,
      may undergo the gel to liquid-crystalline phase transition at the characteristic
      temperature, Tm. Our present knowledge about the Tm values for various
      phospholipids is far from complete, although it is necessary to know the Tm value
      for preparing liposomes. In this study, we have derived empirically a general
      expression of Tm = 154.2 + 2.0(delta C) - 142.8(delta C/CL) - 1512.5(1/CL) in
      which two apparent structural parameters, delta C and CL, of a
      phosphatidylcholine molecule and their ratio, delta C/CL, are applied to estimate
      the Tm value of the phosphatidylcholine bilayer in excess water. The parameter
      delta C is the effective chain-length difference, in C-C bond lengths, between
      the two acyl chains for the phosphatidylcholine molecule in the gel-state
      bilayer, and CL is the effective length of the longer of the two acyl chains,
      also in C-C bond lengths. A figure containing 163 calculated Tm values is
      presented, and this information will be useful as a guide for designing
      experiments.

PMID- 1988024
TI  - Human von Willebrand factor gene and pseudogene: structural analysis and
      differentiation by polymerase chain reaction.
AB  - Structural analysis of the von Willebrand factor gene located on chromosome 12 is
      complicated by the presence of a partial unprocessed pseudogene on chromosome
      22q11-13. The structures of the von Willebrand factor pseudogene and
      corresponding segment of the gene were determined, and methods were developed for
      the rapid differentiation of von Willebrand factor gene and pseudogene sequences.
      The pseudogene is 21-29 kilobases in length and corresponds to 12 exons (exons 23
      34) of the von Willebrand factor gene. Approximately 21 kilobases of the gene and
      pseudogene were sequenced, including the 5' boundary of the pseudogene. The 3'
      boundary of the pseudogene lies within an 8-kb region corresponding to intron 34
      of the gene. The presence of splice site and nonsense mutations suggests that the
      pseudogene cannot yield functional transcripts. The pseudogene has diverged
      approximately 3.1% in nucleotide sequence from the gene. This suggests a recent
      evolutionary origin approximately 19-29 million years ago, near the time of
      divergence of humans and apes from monkeys. Several repetitive sequences were
      identified, including 4 Alu, one Line-1, and several short simple sequence
      repeats. Several of these simple repeats differ in length between the gene and
      pseudogene and provide useful markers for distinguishing these loci. Sequence
      differences between the gene and pseudogene were exploited to design
      oligonucleotide primers for use in the polymerase chain reaction to selectivity
      amplify sequences corresponding to exons 23-34 from either the von Willebrand
      factor gene or the pseudogene. This method is useful for the analysis of gene
      defects in patients with von Willebrand disease, without interference from
      homologous sequences in the pseudogene.

PMID- 1988026
TI  - Purification of an equine apotransferrin variant (thyromedin) essential for
      thyroid hormone dependent growth of GH1 rat pituitary tumor cells in chemically
      defined culture.
AB  - Pituitary tumor cells require thyroid hormones for growth in vivo [Sorrentino, J.
      M., Kirkland, W. L., & Sirbasku, D. A. (1976) J. Natl. Cancer Inst. 56, 1155
      1158]. In vitro, GH1 rat pituitary tumor cells were studied in a serum-free
      defined medium (PCM-10) formulated with Ham's F12 and Dulbecco's modified Eagle's
      media (1:1, v/v) supplemented with 2.2 g/L sodium bicarbonate, 15 mM 4-(2-hydroxy
      ethyl)-1-piperazineethanesulfonic acid (pH 7.2), 10 micrograms/mL human
      transferrin, 50 microM ethanolamine, 10 micrograms/mL insulin, 10 ng/mL selenous
      acid, 0.1 nM 3,5,3'-triiodothyronine (T3) and 500 micrograms/mL bovine serum
      albumin and in the same medium without T3 (PCM-0). The cells only grew in PCM-10
      when low concentrations of horse serum were added. Attempts to replace the serum
      factor requirement with known growth factors and adhesion proteins were
      unsuccessful. The Mr 65,000-72,000 serum factor regulating T3-induced growth
      (thyromedin) was purified to homogeneity and identified as equine transferrin R
      and/or D by amino acid sequencing. The ED50 in PCM-10 was 17-40 micrograms/mL
      (260-620 nM) while in PCM-0 half-maximum growth was not achieved at 200
      micrograms/mL. Concentrations of 75 micrograms/mL in PCM-10 caused 80% of serum
      stimulated growth rate. Removal of iron from thyromedin, and assay in iron salts
      reduced PCM-10, increased the specific activity 110-270-fold to ED50 150 ng/mL
      (2.3 nM); at 1.0 micrograms/mL, growth in PCM-10 was 16-fold greater than in PCM
      0. Iron saturation of thyromedin caused total loss of biological activity. We
      conclude that the horse transferrin variant isolated in this report is active as
      apotransferrin.

PMID- 1988027
TI  - The tyrosine-225 to phenylalanine mutation of Escherichia coli aspartate
      aminotransferase results in an alkaline transition in the spectrophotometric and
      kinetic pKa values and reduced values of both kcat and Km.
AB  - Tyrosine-225 is hydrogen-bonded to the 3'-hydroxyl group of pyridoxal 5'
      phosphate in the active site of aspartate aminotransferase. Replacement of this
      residue with phenylalanine (Y225F) results in a shift in the acidic limb of the
      pKa of the kcat/KAsp vs pH profile from 7.1 (wild-type) to 8.4 (mutant). The
      change in the kinetic pKa is mirrored by a similar shift in the
      spectrophotometrically determined pKa of the protonated internal aldimine. Thus,
      a major role of tyrosine-225 is to provide a hydrogen bond that stabilizes the
      reactive unprotonated form of the internal aldimine in the neutral pH range. The
      Km value for L-aspartate and the dissociation constant for alpha-methyl-DL
      aspartate are respectively 20- and 37-fold lower in the mutant than in the wild
      type enzyme, while the dissociation constant for maleate is much less perturbed.
      These results are interpreted in terms of competition between the Tyr225 hydroxyl
      group and the substrate or quasi-substrate amino group for the coenzyme. The
      value of kcat in Y225F is 450-fold less than the corresponding rate constant in
      wild type. The increased affinity of the mutant enzyme for substrates, combined
      with the lack of discrimination against deuterium in the C alpha position of L
      aspartate in Y225F-catalyzed transamination [Kirsch, J. F., Toney, M. D., &
      Goldberg, J. M. (1990) in Protein and Pharmaceutical Engineering (Craik, C. S.,
      Fletterick, R., Matthews, C. R., & Wells, J., Eds.) pp 105-118, Wiley-Liss, New
      York], suggests that the rate-determining step in the mutant is hydrolysis of the
      ketimine intermediate rather than C alpha-H abstraction which is partially rate
      determining in wild type.

PMID- 1988028
TI  - Minimal peptide length for interaction of amphipathic alpha-helical peptides with
      phosphatidylcholine liposomes.
AB  - The interactions of a series of amphipathic alpha-helical peptides containing
      from 6 to 18 amino acid residues with dipalmitoylphosphatidylcholine (DPPC) and
      dimyristoylphosphatidylcholine (DMPC) were studied by optical and calorimetric
      methods. Several peptides rapidly decreased the turbidity of DMPC and DPPC
      liposomes when mixed at the phase transition temperatures of the lipids. The
      extent of the clearing depended upon the chain length of the peptides, with the
      most effective clearing attained with peptides 10-12 residues in length. An eight
      residue peptide was somewhat less effective and a six-residue peptide had no
      effect on liposome structure. The peptides formed small micellar structures, as
      judged by gel filtration chromatography. The effects of the peptides on the phase
      transitions of the lipids were examined by differential scanning calorimetry. The
      peptides that were most effective in disrupting the liposomes and forming clear
      micelles were also most effective in reducing the enthalpy of the gel to liquid
      crystalline phase transition of the lipid. The addition of DMPC or DPPC liposomes
      to the peptides increased the magnitude of the negative bonds at 208 and 222 nm
      in circular dichroism measurements, consistent with the expected formation of
      alpha-helical structure on binding to lipid. The extent of burial of the single
      tryptophan residue in the peptides was determined by fluorescence spectroscopy.
      In peptides that bound to lipid, the tryptophan was in a less solvent-exposed
      environment in the presence of lipid, as evidenced by a blue shift in the
      fluorescence emission maximum of the peptide.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1988029
TI  - Heparin-binding lectin from human placenta: further characterization of ligand
      binding and structural properties and its relationship to histones and heparin
      binding growth factors.
AB  - We have previously demonstrated that the heparin-binding lectin of human placenta
      dissociates into up to four distinct polypeptides with molecular weights of
      14,400, 15,000, 16,200, and 16,700 (Kohnke-Godt, B., & Gabius, H.-J. (1989)
      Biochemistry 28, 6531-6538). Stable complexes to ligands can shift the molecular
      weight appearance of the lectin to higher values. They can be dissociated in the
      additional presence of 9 M urea or by enzymatic degradation of heparin in model
      studies. The binding of heparin is rather stable over a range of salt
      concentrations from 1 to 3 M NaCl. Chemical modification with group-specific
      reagents to arginine, lysine, histidine, tyrosine, and tryptophan results in
      substantial inactivation of binding activity. Further amino-terminal sequence
      analyses point to a high-scoring relationship in this region to histone
      sequences, namely, histone H2B, but to no published sequences for any heparin
      binding growth factor. Calculation of relatedness on the basis of differences in
      amino acid composition corroborates the conclusion of molecular distinction
      between the lectin, histones H2A and H2B, and the fibroblast growth factor as
      well as angiogenin. Histones only weakly agglutinate type II erythrocytes in
      contrast to the lectin. The immobilized lectin exhibits two classes of binding
      sites with KD values of 3 and 110 nM in contrast to one estimated KD value of 250
      nM with a commercially available histone fraction. Both fractions retain binding
      activity to biotinylated heparin in transblots and are immunologically cross
      reactive to antibodies, raised against the lectin as antigen. Subcellular
      fractionation clearly demonstrates that heparin-inhibitable hemagglutination
      activity and immunologically cross-reactive protein bands, characteristic for the
      lectin, but not unequivocally distinguishable from certain histone fractions in
      blots, are not confined to the nuclear fraction in the human placenta.

PMID- 1988030
TI  - Orientation of cytochromes P450 in the endoplasmic reticulum.
AB  - The orientation of eukaryotic cytochromes P450, with respect to the membrane of
      the endoplasmic reticulum, has been investigated. There is now good evidence that
      the tertiary structure of these proteins is essentially the same as that of the
      soluble bacterial isoenzyme cytochrome P450CI, with the exception of an extension
      at the N-terminus which is thought to form a membrane-anchoring sequence. The
      remainder of the molecule protrudes from the cytosolic face of the membrane so
      that it can interact with substrates and electron-donating proteins. Two models
      based on this structure have been considered, in which the plane of the heme of
      cytochrome P450 is oriented either parallel with or perpendicular to the plane of
      the membrane of the endoplasmic reticulum. The validity of these models has been
      assessed from the results of studies involving the binding of antipeptide
      antibodies directed toward known regions of cytochromes P450, modeling of the
      interaction of cytochrome P450 with cytochrome b5, proposed intramolecular
      movements of cytochrome P450 during its catalytic cycle, and the partitioning of
      substrates for cytochrome P450 between the cytosol and membrane. It is concluded
      that cytochrome P450 is most likely oriented such that the heme is not fixed
      horizontal to the plane of the membrane of the endoplasmic reticulum and may well
      lie with the heme perpendicular to the membrane.

PMID- 1988031
TI  - Genomic sequence and organization of two members of a human lectin gene family.
AB  - We have isolated and sequenced the genomic DNA encoding a human dimeric soluble
      lactose-binding lectin. The gene has four exons, and its upstream region contains
      sequences that suggest control by glucocorticoids, heat (environmental) shock,
      metals, and other factors. We have also isolated and sequenced three exons of the
      gene encoding another human putative lectin, the existence of which was first
      indicated by isolation of its cDNA. Comparisons suggest a general pattern of
      genomic organization of members of this lectin gene family.

PMID- 1988032
TI  - Packing characteristics of highly unsaturated bilayer lipids: Raman spectroscopic
      studies of multilamellar phosphatidylcholine dispersions.
AB  - The thermotropic properties and acyl chain packing characteristics of
      multilamellar dispersions of highly unsaturated lipids were examined by Raman
      spectroscopy. Bilayer assemblies were composed of POPC (1-palmitoyl-2
      oleoylphosphatidylcholine), PAPC (1-palmitoyl-2-arachidonylphosphatidylcholine),
      and PDPC (1-palmitoyl-2-docosahexaenoylphosphatidylcholine), lipid systems
      possessing saturated sn-1 chains and unsaturated sn-2 chains with one, four, and
      six double bonds, respectively. Raman spectra were recorded in the acyl chain
      2800-3100-cm-1 carbon-hydrogen (C-H) stretching and 1100-1200-cm-1 carbon-carbon
      (C-C) stretching mode regions, spectral intervals reflecting both the inter- and
      intrachain order/disorder properties of the various lipid dispersions. In order
      to obtain C-H stretching mode spectra relevant solely to the sn-1 chains of PAPC
      and PDPC, liquid-phase spectra of arachidonic and docosahexaenoic acid,
      respectively, were subtracted from the observed phospholipid spectra. The
      unsaturated sn-2 chains of PAPC and PDPC undergo minimal conformational
      reorganizations as the bilayers pass from the gel to liquid-crystalline phases.
      Phase transition temperatures, Tm, derived from statistically fitting the
      temperature-dependent Raman spectral data are approximately -2.5, -22.5, and -3
      degrees C for POPC, PAPC, and PDPC, respectively. As the degree of unsaturation
      increases from POPC to PAPC and PDPC, the cooperativity of the phase transition,
      as measured by its breadth, decreases. Estimates of the transition widths from
      the temperature profiles are approximately 15 degrees C for PAPC and 20 degrees C
      for PDPC. The behavior of various Raman spectral parameters for the lipid gel
      phase reflects the formation of lateral microdomains, or clusters, whose packing
      properties maximize the van der Waals interactions between sn-1 chains.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1988033
TI  - Assembly of a class I tRNA synthetase from products of an artificially split
      gene.
AB  - The aminoacyl-tRNA synthetases arose early in evolution and established the rules
      of the genetic code through their specific interactions with amino acids and RNA
      molecules. About half of these tRNA charging enzymes are class I synthetases,
      which contain similar N-terminal nucleotide-fold-like structures that are joined
      to variable domains implicated in specific protein-tRNA contacts. Here, we show
      that a bacterial synthetase gene can be split into two nonoverlapping segments.
      We split the gene for Escherichia coli methionyl-tRNA synthetase (a class I
      synthetase) at several sites near the interdomain junction, such that one segment
      codes for the nucleotide-fold-containing domain and the other provides
      determinants for tRNA recognition. When the segments are folded together, they
      can recognize and charge tRNA, both in vivo and in vitro. We postulate that an
      early step in the assembly of systems to attach amino acids to specific RNA
      molecules may have involved specific interactions between discrete proteins that
      is reflected in the interdomain contacts of modern synthetases.

PMID- 1988034
TI  - A new role for the transferrin receptor in the release of iron from transferrin.
AB  - Iron removal by pyrophosphate from human serum diferric transferrin and the
      complex of transferrin with its receptor was studied in 0.05 M HEPES or MES
      buffers containing 0.1 M NaCl and 0.01 M CHAPS at 25 degrees C at pH 7.4, 6.4,
      and 5.6. At each pH, the concentration of pyrophosphate was adjusted to achieve
      rates of release amenable to study over a reasonable time course. Released iron
      was separated from protein-bound iron by poly(ethylene glycol) precipitation of
      aliquots drawn from the reaction mixture at various times during the course of a
      kinetic run. The amount of 59Fe label associated with the protein and
      pyrophosphate was determined from the radioactivity of precipitate and
      supernatant, respectively, in each aliquot. Iron removal of 0.05 M pyrophosphate
      at pH 7.4 from diferric transferrin bound to the receptor is considerably slower
      than that from free diferric transferrin, with observed pseudo-first-order rate
      constants of 0.020 and 0.191 min-1, respectively. For iron removal by 0.01 M
      pyrophosphate at pH 6.4, corresponding rate constants are 0.031 and 0.644 min-1.
      However, at pH 5.6, iron removal by 0.001 M pyrophosphate is faster from diferric
      transferrin bound to its receptor than from free transferrin (observed rate
      constants of 0.819 and 0.160 min-1, respectively). Thus, the transferrin receptor
      not only facilitates the removal of iron from diferric transferrin at the low pH
      that prevails in endocytic vesicles but may also reduce its accessibility to iron
      acceptors at extracellular pH, thereby minimizing the likelihood of nonspecific
      release of iron from transferrin at the cell surface.

PMID- 1988035
TI  - Endoproteolytic processing of the human protein C precursor by the yeast Kex2
      endopeptidase coexpressed in mammalian cells.
AB  - The human protein C precursor undergoes extensive co- and posttranslational
      modification during its biosynthesis in the liver. These modifications include
      glycosylation, gamma-carboxylation, and beta-hydroxylation of specific amino
      acids and endoproteolytic processing to remove the pre- and propeptides as well
      as the pair of basic amino acids which connect the light and heavy chains in the
      precursor. Previous studies with a recombinant mammalian expression system have
      indicated that the endopeptidase in several mammalian cell types which recognizes
      and cleaves this dibasic site has a substrate specificity for sites which also
      include a basic amino acid in the -4 position (Foster et al., 1990). Since the
      human protein C precursor has His154 in the -4 position, it is poorly and
      incompletely cleaved in BHK and several other mammalian cell lines and also
      apparently secreted from the liver as a mixed population of mature two-chain and
      precursor one-chain molecules. In the present study, a mammalian expression
      system has been used to study the effect of coexpressing the protein C precursor
      together with the yeast Kex2 endopeptidase which is known to recognize and
      process dibasic pairs within peptide precursors in yeast. Coexpression of the
      KEX2 gene resulted in complete conversion of the protein C precursor to the
      mature two-chain form. Amino-terminal sequencing of the cleavage products has
      indicated that the cleavage occurs in the correct location and that this site is
      preferentially recognized by the yeast endopeptidase within the context of the
      mammalian cell secretory pathway.

PMID- 1988036
TI  - Metabolism of unusual membrane phospholipids in the marine sponge Microciona
      prolifera.
AB  - Sponges are unique in regard to membrane phospholipid composition. Features
      virtually without parallel in other organisms are the predominance of the C26-C30
      polyenoic acids (demospongic acids) in the phosphatidylethanolamines (PE) and the
      attachment of identical acyl groups to the glycerol moiety. The biosynthesis and
      disposition of these unusual phospholipids were followed in the marine sponge
      Microciona prolifera where PE ( delta 5,9-26:2, delta 5,9-26:2) is a major
      molecular species. Incorporation experiments with radiolabeled fatty acids,
      bases, and intact phospholipids revealed the de novo biosynthesis of the two
      major phosphatides, phosphatidylethanolamines (PE) and phosphatidylcholines (PC),
      via the cytidine pathway as in higher animals, with ethanolamine selectively
      incorporated into PE( delta 5,9-26:2, delta 5,9-26:2). Methylation of PE and
      random acyl chain migration across different phospholipid classes were marginal,
      but the exchange of PC for PE, apparently mediated by the action of
      phospholipase, was indicated after uptake of the unnatural PC( delta 9-27:1,
      delta 9-26:1). The present study demonstrates in the most primitive multicellular
      animals a phospholipid metabolic pattern similar to that in higher organisms,
      with unique acyl and phosphoethanolamine transferases apparently involved in the
      biosynthesis of the (demospongic) di-C26-acyl-PE molecular species.

PMID- 1988037
TI  - Mitochondrial metabolism of valproic acid.
AB  - The beta-oxidation of valproic acid (2-propylpentanoic acid), an anticonvulsant
      drug with hepatotoxic side effects, was studied with subcellular fractions of rat
      liver and with purified enzymes of beta-oxidation. 2-Propyl-2-pentenoyl-CoA, a
      presumed intermediate in the beta-oxidation of valproic acid, was chemically
      synthesized and used to demonstrate that enoyl-CoA hydratase or crotonase
      catalyzes its hydration to 3-hydroxy-2-propylpentanoyl-CoA. The latter compound
      was not acted upon by soluble L-3-hydroxyacyl-CoA dehydrogenases from
      mitochondria or peroxisomes but was dehydrogenated by an NAD(+)-dependent
      dehydrogenase associated with a mitochondrial membrane fraction. The product of
      the dehydrogenation, presumably 3-keto-2-propylpentanoyl-CoA, was further
      characterized by fast bombardment mass spectrometry. 3-Keto-2-propylpentanoyl-CoA
      was not cleaved thiolytically by 3-ketoacyl-CoA thiolase or a mitochondrial
      extract but was slowly degraded, most likely by hydrolysis. The availability of 2
      propylpentanoyl-CoA (valproyl-CoA) and its beta-oxidation metabolites facilitated
      a study of valproate metabolism in coupled rat liver mitochondria. Mitochondrial
      metabolites identified by high-performance liquid chromatography were 2
      propylpentanoyl-CoA, 3-keto-2-propylpentanoyl-CoA, 2-propyl-2-pentenoyl- CoA, and
      trace amounts of 3-hydroxy-2-propylpentanoyl-CoA. It is concluded that valproic
      acid enters mitochondria where it is converted to 2-propylpentanoyl-CoA,
      dehydrogenated to 2-propyl-2-pentenoyl-CoA by 2-methyl-branched chain acyl-CoA
      dehydrogenase, and hydrated by enoyl-CoA hydratase to 3-hydroxy-2-propylpentanoyl
      CoA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1988038
TI  - Conformational motion in bacteriorhodopsin: the K to L transition.
AB  - By comparison of the time dependence of linear dichroism and transient absorption
      in light-adapted bacteriorhodopsin over the first 10 microseconds following
      excitation, conformational motion in the protein has been detected. Time-resolved
      linear dichroism and transient absorption scans are reported for several
      wavelengths that probe the K610 and L550 intermediates in the bacteriorhodopsin
      photocycle. The transient absorption scans are insensitive to conformational
      motion and yield the lifetimes of the K610 and L550 intermediates. In contrast,
      the time-resolved linear dichroism scans demonstrate orientational motion of the
      chromophore with a 1.7-microsecond rotational time. The wavelength dependence of
      the least-squares fitting parameters establishes that this motion is associated
      with L550. This motion is discussed in relation to a protein conformational
      change in the course of the bacteriorhodopsin photocycle. No evidence is observed
      for orientational motion on the time scale of the L550----M410 transition.

PMID- 1988039
TI  - A photochemically induced dynamic nuclear polarization study of denatured states
      of lysozyme.
AB  - Photochemically induced dynamic nuclear polarization (photo-CIDNP) techniques
      have been used to examine denatured states of lysozyme produced under a variety
      of conditions. 1H CIDNP difference spectra of lysozyme denatured thermally, by
      the addition of 10 M urea, or by the complete reduction of its four disulfide
      bonds were found to differ substantially not only from the spectrum of the native
      protein but also from that expected for a completely unstructured polypeptide
      chain. Specifically, denatured lysozyme showed a much reduced enhancement of
      tryptophan relative to tyrosine than did a mixture of blocked amino acids with
      the same composition as the intact protein. By contrast, the CIDNP spectrum of
      lysozyme denatured in dimethyl sulfoxide solution was found to be similar to that
      expected for a random coil. It is proposed that nonrandom hydrophobic
      interactions are present within the denatured states of lysozyme in aqueous
      solution and that these reduce the reactivity of tryptophan residues relative to
      tyrosine residues. Characterization of such interactions is likely to be of
      considerable significance for an understanding of the process of protein folding.

PMID- 1988040
TI  - Irreversible inhibition of serine proteases by peptide derivatives of (alpha
      aminoalkyl)phosphonate diphenyl esters.
AB  - Peptidyl derivatives of diphenyl (alpha-aminoalkyl)phosphonates have been
      synthesized and are effective and specific inhibitors of serine proteases at low
      concentrations. Z-PheP(OPh)2 irreversibly reacts with chymotrypsin (kobsd/[I] =
      1200 M-1 s-1) and does not react with two elastases. The best inhibitor for most
      chymotrypsin-like enzymes including bovine chymotrypsin, cathepsin G, and rat
      mast cell protease II is the tripeptide Suc-Val-Pro-PheP(OPh)2 which corresponds
      to the sequence of an excellent p-nitroanilide substrate for several chymases.
      The valine derivative Z-ValP(OPh)2 is specific for elastases and reacts with
      human leukocyte elastase (HLE, 280 M-1 s-1) but not with chymotrypsin. The
      tripeptide Boc-Val-Pro-ValP(OPh)2, which has a sequence found in a good
      trifluoromethyl ketone inhibitor of HLE, is the best inhibitor for HLE (kobsd/[I]
      = 27,000 M-1 s-1) and porcine pancreatic elastase (PPE, kobsd/[I] = 11,000 M-1 s
      1). The rates of inactivation of chymotrypsin by MeO-Suc-Ala-Ala-Pro-PheP(OPh)2
      and PPE and HLE by MeO-Suc-Ala-Ala-Pro-ValP(OPh)2 were decreased 2-5-fold in the
      presence of the corresponding substrate, which demonstrates active site
      involvement. Only one of two diastereomers of Suc-Val-Pro-PheP(OPh)2 reacts with
      chymotrypsin (146,000 M-1 s-1), and the enzyme-inhibitor complex had one broad
      signal at 25.98 ppm in the 31P NMR spectrum corresponding to the Ser-195
      phosphonate ester. Phosphonylated serine proteases are extremely stable since the
      half-time for reactivation was greater than 48 h for the inhibited elastases and
      7.5-26 h for chymotrypsin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1988041
TI  - Structure of human milk bile salt activated lipase.
AB  - The structure and some functional sites of human milk bile salt activated lipase
      (BAL) were studied by cDNA cloning and chemical analysis of the enzyme. Eighteen
      cDNA clones of human BAL were identified from lactating human breast cDNA
      libraries in lambda gt11 and lambda gt10 with antibody and synthetic
      oligonucleotides as probes. The sequence of four clones was sufficient to
      construct a 3018-bp BAL cDNA structure. This sequence codes for an open reading
      frame of 742 amino acid residues. There is a putative signal sequence of 20
      residues which is followed by the amino-terminal sequence of BAL, and the mature
      BAL contains 722 amino acid residues. The cDNA sequence also contains a 678-base
      5'-untranslated sequence, a 97-base 3'-untranslated region, and a 14-base poly(A)
      tail. The sequence of a 1.8-kbp insert of clone G10-4A differs from that of the
      other cDNA in that it contains a deletion of 198 bases (1966-2163) corresponding
      to 66 amino acid residues. By use of BAL cDNA as probe, it was found that the
      major molecular species of BAL mRNA in human mammary gland HBL-100 cells had a
      size of 2.9 kb and two minor species had sizes of 3.8 and 5.1 kb by Northern blot
      analyses. The deduced BAL protein structure contains in the carboxyl-terminal
      region 16 repeating units of 11 amino acids each. The repeating units have the
      basic structure Pro-Val-Pro-Pro-Thr-Gly-Asp-Ser-Gly-Ala-Pro with only minor
      substitutions. The amino acid sequence of human BAL is related to that of
      pancreatic lysophospholipase, cholesterol esterase, cholinesterase,
      acetylcholinesterase, and thyroglobulin. Ten of the 14 cyanogen bromide fragments
      of diisopropyl fluorophosphate inhibited human milk BAL were isolated, determined
      for N-terminal sequences, analyzed for amino sugars, and tested for some
      functional properties. These chemical studies established that the active site of
      human milk BAL is located at serine-194, the N-glycosylation site is present at
      asparagine-187, the O-glycosylation region is in the 16 repeating units near the
      C-terminus, and the heparin binding domain is in the N-terminal region. We have
      also determined the location of disulfide bridges as Cys64-Cys80 and Cys246
      Cys257. The cyanogen bromide cleavage and the partial sequencing of CNBr peptides
      also confirmed the location of methionines in the polypeptide chain as well as
      the deduced cDNA sequence of BAL.

PMID- 1988042
TI  - Kinetic partitioning between the exonuclease and polymerase sites in DNA error
      correction.
AB  - We present a kinetic partitioning mechanism by which the highly efficient 3'---
      5' exonuclease activity of T7 DNA polymerase maximizes its contribution to
      replication fidelity with minimal excision of correctly base-paired DNA. The
      elementary rate constants for the proposed mechanism have been measured directly
      from single-turnover experiments by using rapid chemical quench-flow techniques.
      The exonuclease activity of T7 DNA polymerase toward single-stranded DNA is quite
      fast (kx greater than 700 s-1). This rapid exonuclease is restrained with double
      stranded DNA by a kinetic partitioning mechanism that favors the binding of the
      DNA to the polymerase site to prevent the rapid degradation of matched DNA and
      yet allows selective removal of mismatched DNAs. Both matched and mismatched DNAs
      bind tightly to the polymerase site, with approximately equal affinities, Kdp =
      20 and 10 nM, respectively. Selective removal of the mismatch is governed by the
      rate of transfer of the DNA from the polymerase to the exonuclease site (kp---
      x). The rapid excision of matched DNA is limited by a slow transfer rate (kp----x
      = 0.2 s-1) from the polymerase to the exonuclease site relative to the rate of
      polymerization [kp = 300 s-1; Patel et al. (1991) Biochemistry (first of three
      papers in this issue)]. Removal of mismatched DNA is facilitated by its faster
      transfer rate (kp----x = 2.3 s-1) to the exonuclease site relative to the slow
      rate of polymerization over a mismatch [kpi = 0.012 s-1; Wong et al. (1991)
      Biochemistry (second of three papers in this issue)].(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1988043
TI  - New insights into the structure of An tracts and B'-B' bends in DNA.
AB  - Energy calculations suggest that the currently available NOE distance constraints
      for An tracts in DNA are incapable of distinguishing between structures with a
      narrowed minor groove arising from a large propeller twist with a small
      inclination or from a small propeller twist with a large negative inclination.
      Furthermore, analysis of published data, together with energy estimations,
      strongly argue against bifurcated hydrogen bonding between A and T residues being
      the cause of the anomalous structural properties of An tracts. A conformational
      analysis of the B'-B' junction has been performed in which a single variable base
      pair has been inserted between two regions of B' structure. We have calculated
      low-energy structures for AnGAn,AnCAn,AnTAn,AnCTn, and TnCAn duplexes, where the
      An and Tn tracts were fixed in the anomalous B' conformation. Upon optimization,
      all these structures were found to contain a pronounced roll-like bending into
      the major groove at the site of the insertion. The important factors in the
      formation of these B'-B' bends are the destruction of the B' conformation and the
      concomitant widening of the minor groove at the junction region in order to
      reduce minor groove interstrand base clashes and improve interstrand stacking
      energy. If the B' conformation has strong negative inclination, the improved
      intrastrand stacking energy also contributes to the bending. In calculations of
      duplexes with An and Tn tracts in the B conformation instead of B', the bending
      disappears.

PMID- 1988044
TI  - Solution structure of human calcitonin gene-related peptide by 1H NMR and
      distance geometry with restrained molecular dynamics.
AB  - The structure of human calcitonin gene-related peptide 1 (hCGRP-1) has been
      determined by 1H NMR in a mixed-solvent system of 50% trifluoroethanol/50% H2O at
      pH 3.7 and 27 degrees C. Complete resonance assignment was achieved by using two
      dimensional methods. Distance restraints for structure calculations were obtained
      by semiquantitative analysis of intra- and interresidue nuclear Overhauser
      effects; in addition, stereospecific or X1 rotamer assignments were obtained for
      certain side chains. Structures were generated from the distance restraints by
      distance geometry, followed by refinement using molecular dynamics, and were
      compared with experimental NH-C alpha H coupling constants and amide hydrogen
      exchange data. The structure of hCGRP-1 in this solvent comprises an amino
      terminal disulfide-bonded loop (residues 2-7) leading into a well-defined alpha
      helix between residues 8 and 18; thereafter, the structure is predominantly
      disordered, although there are indications of a preference for a turn-type
      conformation between residues 19 and 21. Comparison of spectra for the homologous
      hCGRP-2 with those of hCGRP-1 indicates that the conformations of these two forms
      are essentially identical.

PMID- 1988045
TI  - Reconstitution of the diiron sites in hemerythrin and myohemerythrin.
AB  - The first reconstitutions of functional diiron sites in the nonheme O2-carrying
      proteins hemerythrin (Hr) and myohemerythrin (myoHr) have been achieved. Both
      proteins are reconstituted under anaerobic conditions, and the procedure consists
      of (i) denaturation of the native met form with 6 M guanidinium chloride in the
      presence of sodium dithionite and 2,2'-dipyridyl, (ii) separation of the
      apoprotein from the other reagents and products, (iii) addition of an iron(II)
      stock solution to the apoprotein in the presence of 2-mercaptoethanol, and (iv)
      several cycles of slow dilution and reconcentration by ultrafiltration to remove
      excess reagents. Iron analyses indicate that the apoproteins have been
      essentially completely freed of iron and that reconstituted Hr contains its full
      complement of iron, i.e., approximately 2 Fe/subunit. Ferrous rather than ferric
      iron appears to be necessary for recovery of the native structures for both myoHr
      and Hr. In the case of Hr, reconstitution was successful only when iron(II) was
      added to apoHr prior to removal of denaturant. ApoHr is essentially insoluble at
      pH 7 in the absence of denaturants but remains soluble when denaturant is removed
      in the presence of ferrous iron, which leads to recovery of the octameric
      structure containing all of its diiron sites. Iron(II) apparently stabilizes the
      native or a nearly native structure during reconstitution. OxymyoHr and oxyHr are
      the major initial products of reconstitution. The yield of oxymyoHr from apomyoHr
      was approximately 87%. In contrast to reconstituted oxymyoHr, where essentially
      all of the iron appears to be functional, approximately 30% of the diiron sites
      in the reconstituted oxyHr are unable to bind O2 at ambient p(O2).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1988046
TI  - Correlation between mutational destabilization of phage T4 lysozyme and increased
      unfolding rates.
AB  - The thermodynamics and kinetics of unfolding of 28 bacteriophage T4 lysozyme
      variants were compared by using urea gradient gel electrophoresis. The mutations
      studied cause a variety of sequence changes at different residues throughout the
      polypeptide chain and result in a wide range of thermodynamic stabilities. A
      striking relationship was observed between the thermodynamic and kinetic effects
      of the amino acid replacements: All the substitutions that destabilized the
      native protein by 2 kcal/mol or more also increased the rate of unfolding. The
      observed increases in unfolding rate corresponded to a decrease in the activation
      energy of unfolding (delta Gu) at least 35% as large as the decrease in
      thermodynamic stability (delta Gu). Thus, the destabilizing lesions bring the
      free energy of the native state closer to that of both the unfolded state and the
      transition state for folding and unfolding. Since a large fraction of the
      mutational destabilization is expressed between the transition state and the
      native conformation, the changes in folding energetics cannot be accounted for by
      effects on the unfolded state alone. The results also suggest that interactions
      throughout much of the folded structure are altered in the formation of the
      transition state during unfolding.

PMID- 1988047
TI  - Membrane phospholipids as an energy source in the operation of the visual cycle.
AB  - Biology depends on the coupling of the free energy of hydrolysis of phosphate
      esters, such as ATP, to drive processes which would otherwise be
      thermodynamically unfavorable. Carboxyl esters are like phosphate esters in their
      ability to hydrolyze with substantial negative free energies, enabling them to
      participate in group transfer processes as well. In particular, membrane
      phospholipids constitute an enormous store of potential energy that could be used
      to fuel energetically unfavorable processes. One such process involves the
      biosynthesis of 11-cis-retinal, the chromophore of rhodopsin, from all-trans
      retinol (vitamin A). The difference in free energy between an all-trans retinoid
      and its corresponding 11-cis retinoid is approximately 4 kcal/mol. This energy is
      provided for in a minimally two-step process involving membrane phospholipids as
      the energy source. First, all-trans-retinol is esterified in the retinal pigment
      epithelium by lecithin retinol acyl transferase (LRAT) to produce an all-trans
      retinyl ester. Second, this ester is transformed into 11-cis-retinol by an
      isomerohydrolase in a process that couples the negative free energy of hydrolysis
      of the acyl ester to the formation of the strained 11-cis-retinol.

PMID- 1988048
TI  - Molecular structure of an apolipoprotein determined at 2.5-A resolution.
AB  - The three-dimensional structure of an apolipoprotein isolated from the African
      migratory locust Locusta migratoria has been determined by X-ray analysis to a
      resolution of 2.5 A. The overall molecular architecture of this protein consists
      of five long alpha-helices connected by short loops. As predicted from amino acid
      sequence analyses, these helices are distinctly amphiphilic with the hydrophobic
      residues pointing in toward the interior of the protein and the hydrophilic side
      chains facing outward. The molecule falls into the general category of up-and
      down alpha-helical bundles as previously observed, for example, in cytochrome c'.
      Although the structure shows the presence of five long amphiphilic alpha-helices,
      the alpha-helical moment and hydrophobicity of the entire molecule fall into the
      range found for normal globular proteins. Thus, in order for the amphiphilic
      helices to play a role in the binding of the protein to a lipid surface, there
      must be a structural reorganization of the protein which exposes the hydrophobic
      interior to the lipid surface. The three-dimensional motif of this apolipoprotein
      is compatible with a model in which the molecule binds to the lipid surface via a
      relatively nonpolar end and then spreads on the surface in such a way as to cause
      the hydrophobic side chains of the helices to come in contact with the lipid
      surface, the charged and polar residues to remain in contact with water, and the
      overall helical motif of the protein to be maintained.

PMID- 1988049
TI  - An assessment of the mechanism of initial electron transfer in bacterial reaction
      centers.
AB  - Subpicosecond time-resolved photodichroism measurements on Rhodobacter
      sphaeroides R26 reaction centers are reported in the key region between 620 and
      740 nm, where the anions of both bacteriopheophytin and bacteriochlorophyll
      (BChl) have their most diagnostic absorption bands. These measurements fail to
      resolve clearly the formation of a reduced BChl species. The implications of this
      for elucidating the role of the accessory BChl in the initial stage of charge
      separation are discussed.

PMID- 1988050
TI  - Catalysis of the oxidative folding of ribonuclease A by protein disulfide
      isomerase: dependence of the rate on the composition of the redox buffer.
AB  - The velocity of the oxidative renaturation of reduced ribonuclease A catalyzed by
      protein disulfide isomerase (PDI) is strongly dependent on the composition of a
      glutathione/glutathione disulfide redox buffer. As with the uncatalyzed,
      glutathione-mediated oxidative folding of ribonuclease, the steady-state velocity
      of the PDI-catalyzed reaction displays a distinct optimum with respect to both
      the glutathione (GSH) and glutathione disulfide (GSSG) concentrations. Optimum
      activity is observed at [GSH] = 1.0 mM and [GSSG] = 0.2 mM. The apparent kcat at
      saturating RNase concentration is 0.46 +/- 0.05 mumol of RNase renatured min-1
      (mumol of PDI)-1 compared to the apparent first-order rate constant for the
      uncatalyzed reaction of 0.02 +/- 0.01 min-1. Changes in GSH and GSSG
      concentration have a similar effect on the rate of both the PDI-catalyzed and
      uncatalyzed reactions except under the more oxidizing conditions employed, where
      the catalytic effectiveness of PDI is diminished. The ratio of the velocity of
      the catalyzed reaction to that of the uncatalyzed reaction increases as the
      quantity [GSH]2/[GSSG] increases and approaches a constant, limiting value at
      [GSH]2/[GSSG] greater than 1 mM, suggesting that a reduced, dithiol form of PDI
      is required for optimum activity. As long as the glutathione redox buffer is
      sufficiently reducing to maintain PDI in an active form [( GSH]2/[GSSG] greater
      than 1 mM), the rate acceleration provided by PDI is reasonably constant,
      although the actual rate may vary by more than an order of magnitude. PDI
      exhibits half of the maximum rate acceleration at a [GSH]2/[GSSG] of 0.06 +/-
      0.01 mM.

PMID- 1988051
TI  - Catalysis of the oxidative folding of ribonuclease A by protein disulfide
      isomerase: pre-steady-state kinetics and the utilization of the oxidizing
      equivalents of the isomerase.
AB  - At low concentrations of a glutathione redox buffer, the protein disulfide
      isomerase (PDI) catalyzed oxidative renaturation of reduced ribonuclease A
      exhibits a rapid but incomplete activation of ribonuclease, which precedes the
      steady-state reaction. This behavior can be attributed to a GSSG-dependent
      partitioning of the substrate, reduced ribonuclease, between two classes of
      thiol/disulfide redox forms, those that can be converted to active ribonuclease
      at low concentrations of GSH and those that cannot. With catalytic concentrations
      of PDI and near stoichiometric concentrations of glutathione disulfide,
      approximately 4 equiv (2 equiv of ribonuclease disulfide) of GSH are formed very
      rapidly followed by a slower formation of GSH, which corresponds to an additional
      2 disulfide bond equiv. The rapid formation of RNase disulfide bonds and the
      subsequent rearrangement of incorrect disulfide isomers to active RNase are both
      catalyzed by PDI. In the absence of GSSG or other oxidants, disulfide bond
      equivalents of PDI can be used to form disulfide bonds in RNase in a
      stoichiometric reaction. In the absence of a glutathione redox buffer, the rate
      of reduced ribonuclease regeneration increases markedly with increasing PDI
      concentrations below the equivalence point; however, PDI in excess over
      stoichiometric concentrations inhibits RNase regeneration.

PMID- 1988052
TI  - Rat mast cell carboxypeptidase: amino acid sequence and evidence of enzyme
      activity within mast cell granules.
AB  - The amino acid sequence of rat mast cell carboxypeptidase has been determined.
      The major form has 308 residues; a minor form has an additional (glutamyl)
      residue at the amino terminus that may indicate an alternate cleavage site during
      zymogen activation. The enzyme is homologous to pancreatic carboxypeptidases A
      and B, with conservation of the functional amino acid residues of the active
      site. The putative substrate binding site resembles that of carboxypeptidase A,
      although other structural features bear more similarity to carboxypeptidase B.
      Mast cell carboxypeptidase retains enzymatic activity toward a peptide substrate
      (angiotensin I) while bound within the granular matrix of the rat connective
      tissue mast cells. Evidence is presented to suggest that a cluster of positively
      charged lysyl and arginyl residues binds the enzyme to the negatively charged
      heparin of the granular matrix but leaves the active site exposed to bind and
      cleave peptide substrates.

PMID- 1988053
TI  - Brain calbindin-D28k and an Mr 29,000 calcium binding protein in cerebellum are
      different but related proteins: evidence obtained from sequence analysis by
      tandem mass spectrometry.
AB  - A calcium binding protein of Mr 29,000 which cross-reacts with antibodies raised
      against chick calbindin-D28k was previously reported to be present in rat
      cerebellum [Pochet, R., Parmentier, M., Lawson, D. E. M., & Pasteels, J. L.
      (1985) Brain Res. 345, 251-254]. It was suggested that the Mr 29,000 protein
      represents another form of calbindin-D28k. In our laboratory we were able to
      identify Mr 28,000 and 29,000 proteins in rat, human, and chick cerebellum by
      their ability to bind 45Ca in a 45Ca blot assay. Two calcium binding proteins of
      Mr 27,680 and 29,450 were isolated from rat cerebelli by the use of gel
      permeation chromatography and preparative gel electrophoresis. After reverse
      phase high-performance liquid chromatography (HPLC) the proteins were sequenced.
      Sequence analysis by tandem mass spectrometry indicated only 52% identity between
      the rat cerebellar Mr 28,000 and 29,000 proteins. Thus they are not different
      forms of the same protein, as previously suggested. Eighty-nine percent identity
      was observed between the rate cerebellar Mr 29,000 protein and chick calretinin
      [Rogers, J. H. (1987) J. Cell Biol. 105, 1343-1353]. The difference in identity
      between the rat cerebellar Mr 29,000 protein and chick calretinin may be due to
      species differences, and thus this protein is most likely rat calretinin.
      However, barely detectable levels of mRNA and weak immunoreactivity have been
      reported for calretinin in cerebellum. Since we found the Mr 29,000 calcium
      binding protein to be an abundant protein in rat cerebellum, these results
      suggest either posttranscriptional regulation of calretinin in cerebellum or
      species differences.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1988055
TI  - Resonance Raman spectroscopy of bilirubins: band assignments and application to
      bilirubin/lipid complexation.
AB  - Resonance Raman spectra of bilirubins IX alpha, III alpha, and XIII alpha and
      mesobilirubin XIII alpha in alkaline aqueous and chloroform solutions are
      reported. Partial band assignments of bilirubin IX alpha are proposed. The model
      compounds confirm assignments of bands of the Raman spectrum of bilirubin IX
      alpha to each of the two different pyrromethenones. Resonance Raman spectra of
      mesobilirubin IV alpha, vinylneoxanthobilirubinic acid, and
      vinylisoneoxanthobilirubinic acid in alkaline aqueous solution and of the tetra-n
      butylammonium salt of bilirubin IX alpha are used to define markers for the
      presence or absence of internal hydrogen bonds. Interaction of bilirubin dianion
      and sphingomyelin liposomes is studied. The Raman evidence suggests that in the
      bilirubin dianion/liposome complex the intramolecular hydrogen bonds between the
      propionate groups and the lactam NH/CO are ruptured. It is proposed that in the
      complex the bilirubin propionates form ion pairs with the quaternary ammonium ion
      of the choline moiety of sphingomyelin.

PMID- 1988054
TI  - Trifluoperazine binding to mutant calmodulins.
AB  - Trifluoperazine (TFP) binding by 14 calmodulins, including 12 produced by site
      directed mutagenesis, was determined. While vertebrate calmodulin binds 4.2 +/-
      0.2 equiv of TFP, Escherichia coli expressed but unmutated calmodulins bind about
      5.0 +/- 0.5 equiv of TFP. The cause for this difference is not known. The E. coli
      expressed proteins consist of two different series expressed from different
      calmodulin genes, CaMI and SYNCAM. The wild-type genes code for proteins that
      differ by nine conservative amino acid substitutions. Both these calmodulins bind
      5 equiv of TFP with similar affinities, thus none of these conservative
      substitutions has any additional effect on TFP binding. Some altered calmodulins
      (deletion of EE83-84 or SEEE81-84, changing DEE118-120----KKK, M124----I,E120---
      K, or E82----K) have no appreciable effect on TFP binding. Other mutations affect
      either the binding of one TFP (deletion of E84) or about two TFP (changing E84---
      K, EEE82-84----KKK, E67----A, DEQ6-8----KKK, or E11----K). The mutations that
      affect TFP binding are localized to three regions of calmodulin: The amino
      terminal alpha-helix, the central helix between the two globular ends of
      calmodulin, and a calcium-binding site in the second calcium-binding domain. The
      results are consistent with each of these regions either directly participating
      in drug binding or involved structurally in maintaining or inducing the correct
      conformation for TFP binding in the amino-terminal half of calmodulin.

PMID- 1988056
TI  - Identification and characterization of the ligand-binding domain of insulin
      receptor by use of an anti-peptide antiserum against amino acid sequence 241-251
      of the alpha subunit.
AB  - We previously reported that a 23-kDa receptor proteolytic fragment containing an
      insulin-binding site was localized within residues 205-316 in the cysteine-rich
      region of the insulin receptor alpha subunit and postulated that sequence 241-251
      plays a major role in insulin binding [Yip, C. C., Hsu, H., Patel, R. G., Hawley,
      D. M., Maddux, B. A., & Goldfine, I.D. (1988) Biochem. Biophys. Res. Commun. 157,
      321-329]. In the present study, we have used an antiserum raised against a
      synthetic peptide containing sequence 241-251 to test this postulate and to study
      the role of sequence 241-251 in insulin binding. The antiserum immunoprecipitated
      the 23-kDa fragment, confirming our sequence assignment of this fragment. It also
      immunoprecipitated the intact alpha subunit of the insulin receptor that had been
      denatured by reduction and alkylation. However, sequence 241-251 in the native
      receptor was inaccessible to the antiserum since the antiserum did not block
      [125I]iodoinsulin binding and did not precipitate either photoaffinity-labeled
      insulin receptors or insulin receptors labeled with 125I. However, using a
      radioactive photoaffinity probe [( 125I]-AZAP-insulin) that allows cleavage and
      removal of insulin after photolabeling, we found that sequence 241-251 became
      accessible to the antiserum after removal of insulin. We conclude therefore that
      sequence 241-251 forms part of the insulin-binding domain of the insulin receptor
      and that the binding of insulin to the receptor induces a conformational change
      that allows exposure of this domain after removal of insulin. Such a
      conformational change may play a role in activation of the receptor and
      transmembrane signaling.

PMID- 1988057
TI  - Amino acid sequences and Ca2(+)-binding properties of two isoforms of barnacle
      troponin C.
AB  - Much of our knowledge of the relationship between elevation of free sarcoplasmic
      [Ca2+] and skeletal muscle contraction has come from physiological studies on
      barnacle muscle fibers. Little is known, however, about the biochemical
      properties of the barnacle proteins responsible for Ca2+ regulation. In order to
      help rectify this unfortunate situation, we purified the two major isoforms
      (BTnC1 and BTnC2) of troponin C (TnC) from the giant barnacle, Balanus nubilis,
      and determined their amino acid sequences. BTnC2, the more abundant isoform,
      contains 151 amino acid residues and has a calculated molecular weight of 16,838.
      Due to an elongated N-terminus, BTnC1 contains 158 amino acid residues and has a
      calculated molecular weight of 17,984. The two sequences can be aligned from
      their C-termini, with no insertions or deletions, but they are only 61%
      identical. Sequence differences are twice as frequent in the N-terminal halves as
      in the C-terminal halves but occur in all regions of the polypeptides. This
      indicates that BTnC1 and BTnC2 are products of different genes, rather than
      alternative transcripts of a single gene. Both isoforms contain the usual four
      ancestral Ca2(+)-binding regions, numbered I-IV from the N-terminus. Analysis of
      the sequences predicts that functional Ca2(+)-binding sites are present only in
      regions II and IV and that these sites are low-affinity Ca2(+)-specific type
      sites. Direct Ca2(+)-binding measurements using fluorescent Ca2+ indicators show
      that both isoforms bind 2 Ca2+/mol with equal affinity (KCa = 1.3 x 10(5) M-1)
      and the sites appear to be Ca2(+)-specific.

PMID- 1988058
TI  - Molecular cloning of rat cardiac troponin I and analysis of troponin I isoform
      expression in developing rat heart.
AB  - We have isolated and sequenced a cDNA encoding rat cardiac troponin I. The
      predicted amino acid sequence was highly identical with previously reported
      chemically derived amino acid sequences for rabbit and bovine cardiac troponin I.
      Clones for slow skeletal muscle troponin I were also obtained from neonatal rat
      cardiac ventricle by the polymerase chain reaction. The nucleotide sequences of
      these clones were determined to be more than 99% identical with a previously
      reported rat slow skeletal troponin I cDNA [Koppe et al. (1989) J. Biol. Chem.
      264, 14327-14333]. The troponin I clones hybridized to RNA from the appropriate
      muscle from adult animals. However, RNA from fetal and neonatal rat heart also
      hybridized with the slow skeletal troponin I cDNA, demonstrating its expression
      in fetal and neonatal rat heart. Slow skeletal troponin I steady-state mRNA
      levels decreased with increasing age, but cardiac troponin I mRNA levels
      increased through fetal and early neonatal cardiac development. Thus, during
      fetal and neonatal development, slow skeletal and cardiac troponin I isoforms are
      coexpressed in the rat heart and regulated in opposite directions. The degree of
      primary sequence differences in these isoforms, especially at phosphorylation
      sites, may result in important functional differences in the neonatal myocardium.

PMID- 1988059
TI  - Stereochemistry of the microsomal glutathione S-transferase catalyzed addition of
      glutathione to chlorotrifluoroethene.
AB  - The stereochemistry of S-(2-chloro-1,1,2-trifluoroethyl)glutathione formation was
      studied in rat liver cytosol, microsomes, N-ethylmaleimide-treated microsomes,
      9000g supernatant fractions, purified rat liver microsomal glutathione S
      transferase, and isolated rat hepatocytes. The absolute configuration of the
      chiral center generated by the addition of glutathione to chlorotrifluoroethene
      was determined by degradation of S-(2-chloro-1,1,2-trifluoroethyl)glutathione to
      chlorofluoroacetic acid, followed by derivatization to form the diastereomeric
      amides N-(S)-alpha-methylbenzyl-(S)-chlorofluoacetamide and N-(S)-alpha
      methylbenzyl-(R)-chlorofluoroacetamide, which were separated by gas
      chromatography. Native and N-ethylmaleimide-treated rat liver microsomes,
      purified rat liver microsomal glutathione S-transferase, rat liver 9000g
      supernatant, and isolated rat hepatocytes catalyzed the formation of 75-81% (2S)
      S-(2-chloro-1,1,2-trifluoroethyl)glutathione; rat liver cytosol catalyzed the
      formation of equal amounts of (2R)- and (2S)-S-(2-chloro-1,1,2
      trifluoroethyl)glutathione. In rat hepatocytes, microsomal glutathione S
      transferase catalyzed the formation of 83% of the total S-(2-chloro-1,1,2
      trifluoroethyl)glutathione formed. These observations show that the microsomal
      glutathione S-transferase catalyzes the first step in the intracellular,
      glutathione-dependent bioactivation of the nephrotoxin chlorotrifluoroethene.

PMID- 1988061
TI  - Effect of flavin structure and redox state on catalysis by and flavin-pterin
      energy transfer in Escherichia coli DNA photolyase.
AB  - 5-DeazaFAD bound to a hydrophobic site in apophotolyase and formed a stable
      reconstituted enzyme, similar to that observed with FAD. Although stoichiometric
      incorporation was observed, the flavin ring modification in 1-deazaFAD interfered
      with normal binding, decreased protein stability, and prevented formation of a
      stable flavin radical, unlike that observed with FAD. The results suggest that an
      important hydrogen bond is formed between the protein and N (1) in FAD, but not N
      (5), and that there is sufficient space at the normal flavin binding site near N
      (5) to accommodate an additional hydrogen but not near N (1). Catalytic activity
      was observed with enzyme containing 5-deazaFADH2 (42% of native enzyme) or 1
      deazaFADH2 (11% of native enzyme) as its only chromophore, but no activity was
      observed with the corresponding oxidized flavins, similar to that observed with
      FAD and consistent with a mechanism where dimer cleavage is initiated by electron
      donation from excited reduced flavin to substrate. The protein environment in
      photolyase selectively enhanced photochemical reactivity in the fully reduced
      state, as evidenced by comparison with results obtained in model studies with the
      corresponding free flavins. Phosphorescence was observed with free or photolyase
      bound 5-deazaFADH2, providing the first example of a flavin that exhibits
      phosphorescence in the fully reduced state. Formation of an enzyme-substrate
      complex resulted in a nearly identical extent of quenching of 5-deazaFADH2
      phosphorescence (85.1%) and fluorescence (87.5%). The data are consistent with a
      mechanism involving exclusive reaction of substrate with the excited singlet
      state of 5-deazaFADH2, analogous to that proposed for FADH2 in native enzyme.
      Direct evidence for singlet-singlet energy transfer from enzyme-bound 5
      deazaFADH2 to 5,10-CH(+)-H4folate was provided by the fact that pterin
      fluorescence was observed upon excitation of 5-deazaFADH2, accompanied by a
      decrease in 5-deazaFADH2 fluorescence. On the other hand, the fluorescence of
      enzyme-bound pterin was quenched by 5-deazaFADox, consistent with energy transfer
      from pterin to 5-deazaFADox. In each case, the spectral properties of the
      chromophores were consistent with the observed direction of energy transfer and
      indicated that transfer in the opposite direction was energetically unlikely.
      Unlike 5-deazaFAD, energy transfer from pterin to FAD is energetically feasible
      with FADH2 or FADox. The results indicate that the direction of flavin-pterin
      energy transfer at the active site of photolyase can be manipulated by changes in
      the flavin ring or redox state which alter the energy level of the flavin
      singlet.

PMID- 1988060
TI  - Enolpyruvate: chemical determination as a pyruvate kinase intermediate.
AB  - Despite many studies suggesting the role of enolpyruvate as a bound intermediate
      in the pyruvate kinase reaction, direct evidence for it has been lacking. By use
      of a combination of chemical trapping and isolation of a derivative, significant
      amounts of enzyme-bound enolpyruvate have now been demonstrated. The method
      distinguishes enolpyruvate. It is based on reaction of bromine with enolpyruvate
      in acid, derivatization of formed bromopyruvate with thionitrobenzoate, and
      resolution by reversed-phase HPLC of the thioether derivative. As little as 10
      pmol of the thioether derivative could be quantitated reliably. With this method,
      the internal equilibria, including the E.ATP.enolpyruvate intermediate, have been
      determined. Enzyme-enolpyruvate concentration was shown to be pH-dependent.
      Phosphoenolpyruvate also reacts with bromine to form bromopyruvate. To quantitate
      enolpyruvate specifically in a background of phosphoenolpyruvate, advantage was
      taken of phosphoenolpyruvate's much greater stability in acid. When bromide/was
      added 10 min after the acid quench, ketonization of enolpyruvate was complete,
      and only phosphoenolpyruvate was measured. Enolpyruvate is thus determined by
      difference between the bromopyruvate measured with and without delayed bromine
      addition.

PMID- 1988062
TI  - 1H NMR study of the base-pairing reactions of d(GGAATTCC): salt effects on the
      equilibria and kinetics of strand association.
AB  - Previously, we examined the imino proton relaxation of d(GGAATTCC) in order to
      characterize salt and polyamine effects on the base-pair opening kinetics of this
      oligonucleotide [Braunlin, W. H., & Bloomfield, V. A. (1988) Biochemistry 27,
      1184-1191]. Here, we report salt-dependent measurements of the NMR behavior of
      the nonexchangeable base proton resonances of d(GGAATTCC). From chemical shift
      measurements, we find an unexpectedly large salt dependence of Ka, the
      equilibrium constant for helix association. A total of 1.8 +/- 0.3 sodium ions
      are thermodynamically released upon dissociation of the octamer duplex. Most of
      the salt dependence of the equilibrium constant can be traced to a large salt
      dependence of the association rate. Thus, 1.4 +/- 0.2 sodium ions associate
      during the rate-limiting step of helix association. In agreement with our
      previous imino proton results, we also find a significant salt dependence of the
      duplex dissociation rate. Activation energies for helix association are very
      small, and possibly negative; most of the temperature dependence of the
      association equilibrium can be traced to a large activation energy (approximately
      50 kcal/mol) for duplex dissociation.

PMID- 1988063
TI  - Two-dimensional 1H NMR studies of synthetic immobile Holliday junctions.
AB  - Two 32 base pair, four-arm immobile Holliday junctions have been prepared and
      studied by two-dimensional 1H nuclear magnetic resonance (NMR) spectroscopy. Two
      quantum spectroscopy provides scalar (through bond) correlations for the 1'H,
      2'H, and 2''H resonances of the deoxyribose sugar rings and the nonlabile
      cytosine and thymine base protons. Assignments in the deoxyribose sugars are
      extended to the 3'H resonances principally from relayed connectivities in total
      correlation spectra. Severe overlap of resonances in the standard regions of two
      dimensional nuclear Overhauser enhancement (NOE) spectra necessitated the use of
      a unique approach for obtaining sequence-specific assignments of duplex DNA,
      wherein all possible NOE connectivities in the spectra are analyzed. These
      studies of 64-residue structures represent a substantial step forward with
      respect to the size of oligonucleotide for which virtually complete assignments
      are obtained. The assignments form the critical background for the detailed
      analysis of Holliday junction structure and dynamics that is required to address
      key issues in understanding the role of Holliday junctions in genetic
      recombination and repair.

PMID- 1988065
TI  - Hairpin formation in the self-complementary dodecamer d-GGTACGCGTACC and
      derivatives containing GA and IA mispairs.
AB  - The dodecamer d-GGTACGCGTACC and four derivatives with GA and IA mispairs in the
      6,7 and 5,8 positions have been examined in dilute solution and 0.01-0.1 M sodium
      chloride. Concentration dependence of Tm, gel electrophoresis, and equilibrium
      centrifugation indicate that these self-complementary oligomers can form hairpins
      under the present conditions. Thermal transitions measured in the ultraviolet
      primarily represent melting of hairpin to coil [cf. Scheffler et al. (1968,
      1970)]. The Tm values show little or no depression for 6,7 substitution but
      rather large depression for 5,8 replacement. We interpret the results to indicate
      that the 6,7 sequences have two-base loops and five base pair stems and that the
      5,8 sequences have four-base loops and four base pair stems. A concurrent
      theoretical modeling study [Raghunathan et al. (1991) Biochemistry (following
      paper in this issue)] provides support for this interpretation.

PMID- 1988064
TI  - Resonance Raman investigation of ferric iron in horseradish peroxidase and its
      aromatic donor complexes at room and low temperatures.
AB  - Resonance Raman (RR) spectra of the acidic form of FeIII horseradish peroxidase
      (HRP) were obtained at room and low temperatures using B- and Q-band excitation.
      At 296 K, HRP exhibits two sets of porphyrin skeletal stretching frequencies
      which are attributed to a thermal mixture of 5- and 6-coordinate high-spin FeIII
      states. When the temperature is lowered, the observed bands shift to higher
      frequencies, and these are assigned to intermediate- and low-spin states.
      Addition of 40% glycerol has no effect on the spectra at 296 K, but at 20 K, all
      four frequency sets are observed corresponding to the two forms observed at room
      and low temperature in the absence of glycerol. The 296 K RR spectrum of the HRP
      hydroquinone complex is similar to that of free HRP, but conversion to the
      intermediate- and low-spin states is complete at a higher temperature than in the
      free enzyme. Addition of benzohydroxamic acid (BHA) to HRP shifts the RR
      frequencies to those corresponding to a 6-coordinate high-spin species at both
      room and low temperature. Two upsilon (C = C) stretching modes are observed for
      HRP and its donor complexes, indicating that the vinyl groups are inequivalent.
      On BHA binding, one of the vinyl modes and upsilon 37 (Eu) are enhanced,
      suggesting symmetry lowering of the heme site.

PMID- 1988066
TI  - Conformational feasibility of a hairpin with two purines in the loop. 5'-d
      GGTACIAGTACC-3'.
AB  - Structural feasibility and conformational requirements for the sequence 5'-d
      GGTACIAGTACC-3' to adopt a hairpin loop with I6 and A7 in the loop are studied.
      It is shown that a hairpin loop containing only two nucleotides can readily be
      formed without any unusual torsional angles. Stacking is continued on the 5'-side
      of the loop, with the I6 stacked upon C5. The base A7, on the 3'-side of the
      loop, can either be partially stacked with I6 or stick outside without stacking.
      Loop closure can be achieved for both syn and anti conformations of the
      glycosidic torsions for G8 while maintaining the normal Watson-Crick base pairing
      with the opposite C5. All torsional angles in the stem fall within the standard B
      family of DNA helical structures. The phosphodiesters of the loop have
      trans,trans conformations. Loop formation might require the torsion about the C4'
      C5' bond of G8 to be trans as opposed to the gauche+ observed in B-DNA. These
      results are discussed in relation to melting temperature studies [Howard et al.
      (1991) Biochemistry (preceding paper in this issue)] that suggest the formation
      of very stable hairpin structures for this sequence.

PMID- 1988067
TI  - A novel combined chemical-enzymatic synthesis of cross-linked DNA using a
      nucleoside triphosphate analogue.
AB  - A novel method using combined chemical and enzymatic reactions to allow the
      preparation of covalently cross-linked DNA duplexes has been described. The
      method can be used to specifically link two complementary bases of a DNA duplex
      containing all four natural bases. The modified nucleotide 9-(2-deoxy-5-O
      triphospho-beta-D-ribofuranosyl)-N6,N6-ethano -2,6-diaminopurine (6edDTP) was
      prepared by total chemical synthesis and was found to be incorporated into DNA
      duplexes in the place of 2'-deoxyguanosine 5'-O-triphosphate by the Klenow
      fragment of Escherichia coli DNA polymerase I, T4 and T7 DNA polymerases, avian
      myeloma virus reverse transcriptase, and rat DNA polymerase beta. Once
      incorporated, the aziridine of the nucleotide is rapidly opened by the N4 of the
      cytosine on the complementary strand to give cross-linked DNA, where the modified
      nucleotide is covalently joined to the complementary base by an ethano linkage.
      The duplexes produced were found to be recognized as substrates by various DNA
      polymerases. The Km for the incorporation of the 6edDTP into DNA catalyzed by the
      Klenow fragment of E. coli DNA polymerase I was found to be 29 microM, and the
      kcat was found to be 0.014 s-1. The modified nucleoside also served as a
      substrate for terminal deoxynucleotidyltransferase, where it was added to single
      stranded DNA and then hybridized to a complementary strand, after which cross
      linking of the two strands occurred within 1 min.

PMID- 1988068
TI  - Upstream sequence activation of Escherichia coli argT promoter in vivo and in
      vitro.
AB  - Escherichia coli argT promoter in a galK fusion construct is shown by BAL 31
      deletion to require its upstream region for high in vivo activity. The extent of
      activation conferred by the upstream sequence from -130 to -38 is 25-fold. A
      spontaneous mutant containing a T to G transversion at -37 (i.e., the T-37G
      promoter) shows a similar requirement; however, the upstream sequence producing a
      10-fold effect spans only -130 to -60. The difference in upstream sequence
      boundaries between the wild-type and T-37G promoters suggests the possible
      existence of two activating elements. Gel mobility investigation points to the
      presence of bent DNA in the argT promoter, and the bent center was localized to
      the -90 to -95 region by circular permutation analysis. The role of the upstream
      activating sequence (UAS) in promoter function was probed by competitive
      transcription experiments in vitro. Results of this type of analysis indicate
      that the full UAS activates transcription through a combined effect on KB and k2.
      Of these, KB is significantly strengthened by the proximal element, and k2 is
      stimulated to a smaller extent by the distal element. The evidence from deletion
      analysis, gel mobility investigation, and competitive transcription together
      support a "two-element" model of UAS function for the argT promoter.

PMID- 1988070
TI  - pH-dependent charge equilibria between tyrosine-D and the S states in photosystem
      II. Estimation of relative midpoint redox potentials.
AB  - The effect of protonation events on the charge equilibrium between tyrosine-D and
      the water-oxidizing complex in photosystem II has been studied by time-resolved
      measurements of the EPR signal IIslow at room temperature. The flash-induced
      oxidation of YD by the water-oxidizing complex in the S2 state is a monophasic
      process above pH 6.5 and biphasic at lower pHs, showing a slow and a fast phase.
      The half-time of the slow phase increases from about 1 s at pH 8.0 to about 20 s
      at pH 5.0, whereas the half-time of the fast phase is pH independent (0.4-1 s).
      The dark reduction of YD+ was followed by measuring the decay of signal IIslow at
      room temperature. YD+ decays in a biphasic way on the tens of minutes to hours
      time scale. The minutes phase is due to the electron transfer to YD+ from the S0
      state of the water-oxidizing complex. The half-time of this process increases
      from about 5 min at pH 8.0 to 40 min at pH 4.5. The hours phase of YD+ has a
      constant half-time of about 500 min between pH 4.7 and 7.2, which abruptly
      decreases above pH 7.2 and below pH 4.7. This phase reflects the reduction of YD+
      either from the medium or by an unidentified redox component of PSII in those
      centers that are in the S1 state. The titration curve of the half-times for the
      oxidation of YD reveals a proton binding with a pK around 7.3-7.5 that retards
      the electron transfer from YD to the water-oxidizing complex. We propose that
      this monoprotic event reflects the protonation of an amino acid residue, probably
      histidine-190 on the D2 protein, to which YD is hydrogen bonded. The titration
      curves for the oxidation of YD and for the reduction of YD+ show a second proton
      binding with pK approximately 5.8-6.0 that accelerates the electron transfer from
      YD to the water-oxidizing complex and retards the process in the opposite
      direction. This protonation most probably affects the water-oxidizing complex.
      From the measured kinetic parameters, the lowest limits for the equilibrium
      constants between the S0YD+ and the S1YD as well as between the S1YD+ and S2YD
      states were estimated to be 5 and 750-1000, respectively.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 1988069
TI  - Rat hemopexin. Molecular cloning, primary structural characterization, and
      analysis of gene expression.
AB  - A full-length hemopexin cDNA was isolated from a rat liver cDNA library and the
      derived amino acid sequence was obtained. Rat hemopexin shows a 76% amino acid
      homology with human hemopexin. The amino-terminal domain of rat hemopexin
      contains two histidine residues that are conserved in the human and rat sequences
      and are the most likely heme axial ligands. Analogous to human hemopexin, the rat
      hemopexin consists of 10 internal repeating peptide motifs characteristic of the
      pexin gene family. A complete conservation of cysteine residues is seen between
      the human and rat sequences suggesting an identical disulfide bridge structure in
      both proteins. Our analysis of the primary structure of rat hemopexin reveals
      characteristics typical for members of the pexin gene family and suggests a
      conserved evolutionary role for the C-terminal (non-heme-binding) domain of this
      protein. The full-length rat hemopexin cDNA was used to analyze changes in
      hemopexin gene expression during development and experimental inflammation. RNA
      blot analysis showed a single 2.0-kb hemopexin mRNA present in fetal liver at day
      14. Hemopexin-specific mRNA was not detected in embryonic or fetal tissues at
      earlier stages of development and was confined to the liver throughout fetal,
      newborn, and adult life. The abundance of hemopexin mRNA was found to increase
      throughout gestation, with a sharp increase in the first postnatal weeks,
      reaching maximum levels in adult animals. Endotoxin-induced inflammation resulted
      in a 5-fold increase in hepatic hemopexin mRNA content within 48 h without
      associated changes in hemopexin transcript size. Adult animals exposed to
      hyperoxia (95% oxygen) showed a 3-fold increase in hepatic hemopexin mRNA
      content.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1988071
TI  - Intermolecular cross-links mediate aggregation of phospholipid vesicles by
      pulmonary surfactant protein SP-A.
AB  - As the most abundant glycoprotein component of pulmonary surfactant, SP-A (Mr =
      30,000-36,000) plays a central role in the organization of phospholipid bilayers
      in the alveolar air space. SP-A, isolated from lung lavage, exists in oligomeric
      forms (N = 6, 12, 18, ...), mediated by collagen-like triple helices and
      intermolecular disulfide bonds. These protein-protein interactions, involving the
      amino-terminal domain of SP-A, are hypothesized to facilitate the alignment of
      surfactant lipid bilayers into unique tubular myelin structures. SP-A
      reorganization of surfactant lipid was assessed in vitro by quantitating the
      calcium-dependent light scattering properties of lipid vesicle suspensions
      induced by SP-A. Accelerated aggregation of unilamellar vesicles required SP-A
      and at least 3 mM free calcium. The initial rate of aggregation was proportional
      to the concentration of canine SP-A over lipid:protein molar ratios ranging from
      200:1 to 5000:1. Digestion with bacterial collagenase or incubation with
      dithiothreitol (DTT) completely blocked lipid aggregation activity. Both
      treatments decreased the binding of SP-A to phospholipids. The conditions used in
      the DTT experiments (10 mM DTT, nondenaturing Tris buffer, 37 degrees C) resulted
      in the selective reduction and 14C-alkylation of the intermolecular disulfide
      bond involving residue 9Cys, whereas the four cysteines found in the
      noncollagenous domain of SP-A were inefficiently alkylated with [14C]
      iodoacetate. HPLC analysis of tryptic SP-A peptides revealed that these four
      cysteine residues participate in intramolecular disulfide bond formation (138Cys
      229Cys and 207Cys-221Cys). Our data demonstrate the importance of the quaternary
      structure (triple helix and intermolecular disulfide bond) of SP-A for the
      aggregation of unilamellar phospholipid vesicles.

PMID- 1988072
TI  - Mechanism of interaction of vinca alkaloids with tubulin: catharanthine and
      vindoline.
AB  - The interactions of the vinca alkaloid drugs catharanthine and vindoline with
      tubulin have been investigated and compared with those of vinblastine and
      vincristine. Both drugs were found to be less effective in bringing about the
      inhibition of tubulin self-assembly into microtubules than vincristine and
      vinblastine, the drug to protein molar ratio required being 3 orders of magnitude
      greater. An analytical ultracentrifuge study has shown that catharanthine can
      induce the self-association of tubulin into linear indefinite polymers with an
      efficacy that is 75% that of vinblastine or vincristine, the intrinsic
      dimerization constant for the liganded protein being K2 congruent to 1 x 10(5) M
      1. The effect of vindoline was marginally detectable. Binding studies of
      catharanthine using the gel batch and fluorescence perturbation techniques showed
      a polymerization-linked binding of one catharanthine molecule per tubulin alpha
      beta dimer with a binding constant of (2.8 +/- 0.4) x 10(3) M-1. For vindoline,
      binding to tubulin was marginally detectable by fluorescence spectroscopy,
      although addition of vindoline to tubulin did generate a difference spectrum. It
      was concluded that the binding of vinblastine/vincristine to tubulin and its
      consequences are determined by the interaction of the indole part of
      catharanthine with tubulin, the role of vindoline being that of an anchor.

PMID- 1988073
TI  - Ribavirin safety alert.

PMID- 1988074
TI  - Maintaining contact with legislators increases nurses' political clout.

PMID- 1988075
TI  - Variant human breast tumor estrogen receptor with constitutive transcriptional
      activity.
AB  - Since progesterone receptor (PgR) is normally induced by estrogen, breast cancer
      lacking estrogen receptor (ER) would also be expected to lack PgR. However, a
      small percentage of breast cancers are ER- yet PgR+. These tumors might possess
      an ER which is defective in estrogen binding but is still functional in
      stimulating estrogen-responsive genes such as PgR. We have now detected such a
      variant, lacking exon 5 of the hormone-binding domain, using complementary DNA
      amplified by the polymerase chain reaction. This variant was the predominate ER
      RNA expressed in three ER-/PgR+ tumors. Furthermore, the variant ER
      constitutively activates transcription of a normally estrogen-dependent gene
      construct in yeast cells. The variant ER could explain the expression of PgR in
      certain tumors and have therapeutic implications.

PMID- 1988076
TI  - Antitumor activity of 7-N-[[2-[[2-(gamma-L-glutamylamino)ethyl]dithio]ethyl]]
      mitomycin C.
AB  - Through the extensive investigation of new mitomycin C (MMC) derivatives, several
      compounds with disulfide at N-7 were found to show activities superior to MMC
      against murine Sarcoma 180 solid tumor. Among them, 7-N-[[2-[[2-(gamma-L
      glutamylamino)ethyl]dithio]ethyl]]- mitomycin C (KW-2149) was selected for
      further evaluation of antitumor activity and toxicity in mice. KW-2149 exhibited
      activity superior to MMC in increasing survival of i.p. inoculated P388 leukemia
      , M5076 sarcoma-, and B16 melanoma-bearing mice. KW-2149 administered i.v. also
      exhibited superior activity in inhibiting the growth of s.c. inoculated P388
      leukemia, M5076 sarcoma, and colon 26 adenocarcinoma and in increasing survival
      of i.v. inoculated P388 leukemia- and M5076 sarcoma-bearing mice. Furthermore, KW
      2149 remarkably increased the life span of MMC-resistant P388 leukemia- and L1210
      leukemia-bearing mice. KW-2149 and MMC inhibited the growth of human tumors
      inoculated into nude mice. The activity of KW-2149 was prominent in human lung
      carcinoma Lu-65 and Lu-99, bladder carcinoma T24, and epidermoid carcinoma A431.
      KW-2149 was comparable to MMC in decreasing the number of WBC in the peripheral
      blood, and the thrombopenia induced by KW-2149 was mild and recovery was rapid.
      The in vitro anticellular spectrum of KW-2149 against 23 human tumor cell lines
      was similar to that of MMC. However, KW-2149 inhibited the growth of the cell
      lines at concentrations of 10- to 100-fold lower than MMC and showed efficient
      cytotoxicity against MMC-insensitive tumor cell lines. These included lung
      epidermoid carcinoma Calu-1, stomach carcinoma MKN-28, colon adenocarcinoma DLD
      1, colon adenocarcinoma LoVo, bladder carcinoma HT-1197, sarcoma G-292, and
      melanoma SK-MEL-28 cells. These results indicate that KW-2149 bears interesting
      characteristics as a new anticancer drug and warrants further development.

PMID- 1988077
TI  - A double-blind placebo-controlled study with granulocyte-macrophage colony
      stimulating factor during chemotherapy for ovarian carcinoma.
AB  - In a placebo-controlled double-blind dose-finding trial, 15 patients with ovarian
      cancer stage III or IV received daily s.c. 1.5, 3, or 6 micrograms/kg recombinant
      human granulocyte-macrophage colony-stimulating factor (GM-CSF). At each dose
      step three patients received recombinant human GM-CSF, and two received placebo.
      Chemotherapy comprised 6 cycles of carboplatin, 300 mg/m2, and cyclophosphamide,
      750 mg/m2, by i.v. bolus on day 1 every 4 weeks. GM-CSF, given on days 6-12 on an
      outpatient basis, raised the mean leukocyte count on days 7, 10, and 15 and the
      mean neutrophil count on days 7 and 10 at all dose levels as compared with the
      control group. Neutrophil counts of less than 0.5 x 10(9)/liter occurred in 20 of
      22 cycles in the control group and in 5 of 17 cycles at the 6-micrograms/kg/day
      GM-CSF dose level (P less than 0.0005). In comparison with the control group, the
      mean eosinophil count was higher on days 10 and 15 at all GM-CSF doses, as was
      the mean monocyte count on day 15. The mean platelet count was raised at the 3-
      and 6-micrograms GM-CSF doses on days 15 and 22. Chemotherapy dose reduction or
      postponement due to myelotoxicity occurred in 9 of 28 cycles in the placebo
      groups versus 5 of 44 cycles in the GM-CSF group (not significant). Local skin
      infiltrates at the GM-CSF injection sites occurred in 8/9 patients, leading to
      premature removal of two patients from the study. Capillary leakage of 131I
      albumin was increased in all patients 5 days after the first chemotherapy course
      but was not significantly affected by 4 days of GM-CSF treatment. Tumor necrosis
      factor alpha and C-reactive protein serum levels increased during GM-CSF
      administration at the 6-micrograms dose level, but interleukin 6 serum levels
      were not affected. We conclude that a dose of 3 and 6 micrograms/kg/day GM-CSF
      reduces the severity of neutropenia and thrombocytopenia after carboplatin
      cyclophosphamide. This GM-CSF dose does not induce additional capillary leakage.

PMID- 1988078
TI  - Reversible and phorbol ester-specific defect of protein kinase C translocation in
      hepatocytes isolated from phenobarbital-treated rats.
AB  - Phorbol ester-induced translocation of the calcium/phospholipid-dependent protein
      kinase, protein kinase C (PKC), from soluble to particulate cell fractions was
      inhibited in primary cultures of hepatocytes isolated from rats chronically
      exposed to the liver tumor promoter phenobarbital (PB). Inhibition of
      translocation (34%) was significant after a 15-min treatment with 12-O
      tetradecanoylphorbol-13-acetate (TPA, 500 nM); an 85% inhibition was observed
      after 60 min. In contrast, the translocation responses to two non-phorbol ester
      activators of PKC, ATP (1 mM) and arginine-vasopressin (0.1 microM), were not
      significantly impaired. Assessment of total PKC specific activity revealed that
      translocation induced by TPA and the two nonphorbol activators was not associated
      with PKC degradation in hepatocytes from either control or PB-exposed rats. The
      defect in TPA-induced translocation was correlated with an impaired down
      regulation of the hepatocyte surface receptor for epidermal growth factor in
      hepatocytes from PB-exposed rats. Chronic exposure to PB did not affect the total
      content or specific activity of PKC in whole liver, nor did it affect the
      distribution of PKC activity between soluble and particulate fractions in
      unstimulated liver or hepatocytes. However, both the diminished epidermal growth
      factor receptor response and the inhibition of TPA-induced PKC translocation were
      reversed by withdrawal of PB for 2 to 4 weeks. Hepatocytes isolated from female
      rats were found to contain a 3- to 4-fold greater PKC specific activity and
      content than hepatocytes from male rats. However, no sex-related differences were
      observed in PKC distribution or in the modulation of translocation by chronic PB
      exposure and withdrawal. Immunoblotting of partially purified liver extracts
      revealed that the defect in phorbol ester-induced translocation was not caused by
      altered expression of PKC isozymes. PKC isozymes II and III, but not I, were
      detected, and their amounts were unaffected by PB exposure, although higher
      levels were detected in female relative to male livers. These data demonstrate
      reversible inhibition of phorbol ester-induced PKC activation by the liver tumor
      promoter, PB, and suggest that PB alters a component of the PKC-signaling pathway
      other than the expression of PKC isozymes.

PMID- 1988079
TI  - Effect of a chimeric anti-ganglioside GD2 antibody on cell-mediated lysis of
      human neuroblastoma cells.
AB  - An anti-GD2 ganglioside human/mouse chimeric monoclonal antibody, ch14.18, like
      its murine counterpart, 14.G2a, was shown to bind to human neuroblastoma cells.
      This chimeric antibody proved to be more effective than 14.G2a in mediating the
      lysis of neuroblastoma cells with human effector cells, such as granulocytes and
      natural killer cells within the peripheral blood mononuclear cell population. A
      comparison of these two effector cell populations isolated from the same donor
      revealed granulocytes to be more effective than peripheral blood mononuclear
      cells in lysing neuroblastoma cells, which were coated with monoclonal antibody
      ch14.18. Addition of recombinant human granulocyte-macrophage colony-stimulatory
      factor increased ch14.18-mediated lysis of neuroblastoma cells by granulocytes
      but not by peripheral blood mononuclear cells. In fact, granulocytes were
      effective in mediating lysis of neuroblastoma cells coated with ch14.18
      irrespective of whether they were obtained from normal adults or from
      neuroblastoma patients.

PMID- 1988080
TI  - Cellular pharmacology of MX2, a new morpholino anthracycline, in human
      pleiotropic drug-resistant cells.
AB  - We previously reported that MX2, a new morpholino anthracycline, showed marked
      effects on pleiotropic drug-resistant sublines of murine P388 leukemia in vivo as
      well as in vitro. In this study we examine the in vitro cytotoxicity against
      pleiotropic drug-resistant sublines of human tumor cell lines. MX2 was effective
      against multidrug-resistant sublines of four human tumor cell lines; these cells,
      having a 4.8- to 200-fold cross-resistance to Adriamycin (ADM) showed only a 0.7-
      to 2.3-fold resistance to MX2 compared with the sensitive cells. To elucidate the
      mechanism by which MX2 overcomes multidrug resistance, the intracellular
      pharmacology of MX2 in human myelogenous leukemia K562 and its ADM-resistant
      subline (K562/ADM) was examined. Both K562 and K562/ADM cells accumulated MX2
      more easily than ADM, and the intracellular accumulation of MX2 attained a steady
      state in both cell lines within 30 min of incubation at 37 degrees C. The amount
      of MX2 that accumulated in K562/ADM at a steady state was only 1.3 times lower
      than that in K562. However, ADM was accumulated slowly in both cell lines
      compared with MX2, and the intercellular concentration reached a steady state in
      K562/ADM after 90 min of incubation and in K562 after more than 120 min. K562/ADM
      cells accumulated a 3.3-fold lower concentration of ADM than K562 after 120 min
      of exposure. The steady-state concentration of ADM in K562/ADM was 8.3 times
      lower than that of MX2. In addition, greater than 70% of MX2 was retained in both
      cell lines after 150 min of incubation in the absence of this drug. Verapamil, a
      calcium antagonist, hardly augmented the cytotoxicity of MX2 against K562/ADM,
      and no distinct effect of this drug on both the time course and the maximal level
      of accumulation of MX2 was observed. Interestingly, MX2 effectively inhibited
      ATP/Mg2(+)-dependent [3H]vincristine binding to K562/ADM membrane preparations,
      indicating that MX2 could be transported outside the cell by an active efflux
      pump. The high intracellular accumulation and retention of MX2 in K562/ADM
      through the rapid influx of the drug into the cells may be one of the reasons why
      MX2 circumvents pleiotropic drug resistance.

PMID- 1988081
TI  - Effects of choline deficiency and methotrexate treatment upon liver folate
      content and distribution.
AB  - We examined the effects of feeding rats a choline deficient diet, of treating
      rats with low doses of methotrexate (MTX, 0.1 mg/kg, daily), and of combined
      choline deficiency and MTX treatment upon the content and distribution of folates
      in liver. We used a newly devised technique for analysis of folates which
      utilized affinity chromatography followed by high pressure liquid chromatography.
      Compared to control rats, total hepatic folate content decreased by 31% in the
      choline deficient rats, by 48% in the MTX treated rats, and by 60% in rats which
      were both choline deficient and treated with MTX. In extracts of livers from
      control rats, folates were present predominantly as penta (35%) and hexaglutamyl
      (52%) derivatives. The pteridine ring structure distribution of these folates was
      as follows: 48% 5-methyltetrahydrofolate, 14% formylated tetrahydrofolate, and
      39% tetrahydrofolate. In choline deficient animals, there was a decrease in the
      relative concentration of pentaglutamyl folates and an increase in the relative
      concentration of heptaglutamyl folates. In livers from MTX treated animals, MTX
      polyglutamates with 2-5 glutamate residues accumulated. The consequences of MTX
      treatment were: a) an elongation of the glutamate chains of the folates as the
      proportion of hepta- and octaglutamyl derivatives was increased relative to penta
      and hexaglutamyl folates; b) the occurrence of unreduced folic acid; c) a
      decrease in the relative concentration of 5-methyltetrahydrofolate and an
      increase in the relative concentration of formylated tetrahydrofolate, and d) no
      change in the relative concentrations of tetrahydrofolate. In livers from animals
      that were both choline deficient and treated with MTX, the tetrahydrofolate
      concentrations were 50% of control while formylated tetrahydrofolate
      concentrations increased 3-fold. These data are discussed from the standpoint of
      the current understanding of mechanisms that regulate the elongation of the
      glutamic acid chains of folates and those that regulate folate dependent
      synthesis and utilization of one carbon unit.

PMID- 1988082
TI  - Generation and characterization of a recombinant/chimeric B72.3 (human gamma 1).
AB  - We report here the generation and characterization of a recombinant/chimeric
      construct of murine gamma 1 monoclonal antibody (MAb) B72.3, containing the
      murine variable region and a human gamma 1 constant region [designated
      cB72.3(gamma i)]. cB72.3(gamma 1) was generated by first isolating functionally
      rearranged VH and VL genes of B72.3 from partial genomic libraries in phage
      vectors. Construction of mouse-human chimeric heavy and light chain genes was
      performed by inserting restriction fragments carrying VL and VH regions of B72.3
      into unique sites of expression vectors which contains sequences encoding
      constant regions of human kappa and gamma 1, respectively. The expression
      constructs were subsequently electroporated into SP2/0 cells. The transfected
      SP2/0 murine cell line has been shown to synthesize cB72.3(gamma 1) at a level of
      10-20 micrograms/ml. Reciprocal competition radioimmunoassays demonstrated that
      cB72.3(gamma 1), a previously described cB72.3(gamma 4), and native B72.3
      (designated nB72.3) competed similarly. A rat anti-idiotype MAb made against
      nB72.3 was shown to bind equally well to cB72.3(gamma 1) and to the nB72.3.
      Immunochemical studies of the nB72.3, cB72.3(gamma 4), and cB72.3(gamma 1)
      revealed slight differences in size among the three MAb forms on sodium dodecyl
      sulfate gels and revealed a higher isoelectric point for the cB72.3(gamma 1).
      Antibody-dependent cell-mediated cytotoxicity experiments using human lymphokine
      activated killer effector cells indicated better tumor cell killing by the
      cB72.3(gamma 1) than the nB72.3 or cB72.3(gamma 4). Dual label studies of
      coinjected cB72.3(gamma 1) and nB72.3 revealed that both MAbs could efficiently
      localize human tumor xenografts in athymic mice. Pharmacokinetic studies,
      analyzing the blood clearance of cB72.3(gamma 1), cB72.3(gamma 4), and nB72.3 in
      mice, showed that the nB72.3 beta phase of clearance was slower than that of
      other MAb forms. However, when the pharmacokinetic patterns of these three MAbs
      forms were analyzed in monkeys, the cB72.3(gamma 1) and the nB72.3 showed similar
      clearance curves, while the cB72.3(gamma 4) showed a much slower plasma
      clearance. In view of the binding properties of nB72.3 and its ability to
      localize a range of carcinomas in clinical trials, the studies reported here
      demonstrate that the cB72.3(gamma 1) may serve as a potentially useful diagnostic
      and/or therapeutic reagent.

PMID- 1988083
TI  - Urinary excretion of nitrate, N-nitrosoproline, 3-methyladenine, and 7
      methylguanine in a Colombian population at high risk for stomach cancer.
AB  - Urinary excretion levels of nitrate and N-nitrosoproline were determined in 160
      individuals in a Colombian population at high risk for gastric cancer. In 156 of
      these subjects urinary levels of 3-methyladenine and 7-methylguanine were
      determined. Gastric biopsy specimens were obtained from 118 individuals and were
      histologically characterized according to pathological criteria into the
      following groups: normal, superficial gastritis, chronic atrophic gastritis,
      chronic atrophic gastritis with intestinal metaplasia, and dysplastic. The
      histological changes were correlated with the four variables listed above. There
      were no significant differences in the excretion of nitrate, N-nitrosoproline, 3
      methyladenine, or 7-methylguanine in subjects with different pathological
      changes. A statistically significant correlation was present between nitrate and
      N-nitrosoproline excretion in the total population group (r = 0.297, P = 0.0001).
      A highly significant correlation (r = 0.56, P = 0.0002) was noted for urinary
      nitrate and N-nitrosoproline excretion in individuals with intestinal metaplasia
      and dysplasia. An increase in the urinary excretion of 3-methyladenine and 7
      methylguanine was associated with tobacco smoking in the total population group.

PMID- 1988084
TI  - The inhibition of tumor growth by tumor mass.
AB  - Evidence suggests that a tumor behaves, in its pattern of growth, like an
      integrated organ rather than a collection of independently growing cells. Tumor
      growth tends to slow progressively as size increases and to undergo compensatory
      growth after partial resection. Consequently, therapies that reduce tumor mass
      may tend to accelerate the growth of the remaining tumor and tumor metastases. An
      approach to therapy based upon a simulated increase in tumor mass may be worthy
      of consideration.

PMID- 1988085
TI  - Altered protein kinase C activity in biopsies of human colonic adenomas and
      carcinomas.
AB  - Protein kinase C (PK-C) seems to be involved in the regulation of growth and
      differentiation of normal epithelial cells. Colonic adenomas and carcinomas show
      increased proliferation and decreased differentiation. We investigated the
      activity and subcellular distribution of PK-C in biopsies of normal, neoplastic,
      and malignant colonic epithelium to evaluate alterations in enzyme activity. In
      the control group (n = 7), the activity of PK-C was highest in the distal ileum
      (597 pmol/min/mg protein) and declined to the lowest amounts in rectal mucosa
      (225 pmol/min/mg protein). In patients with colonic adenomas (n = 16), total PK-C
      activity was significantly reduced as compared to adjacent mucosa (146 versus 336
      pmol/min/mg protein, P less than 0.05) and to values determined in the control
      group (372 pmol/min/mg protein, P less than 0.01). The reduction of total PK-C
      activity in the adenoma group was even more evident in intraindividual comparison
      to paired adjacent mucosa (41.8% of adjacent mucosa, P less than 0.001). Specific
      activity of membrane-associated PK-C was equally decreased in colonic adenomas
      (36.3 pmol/min/mg protein) when compared to adjacent mucosa (102 pmol/min/mg
      protein, P less than 0.05) or to the control group (107 pmol/min/mg protein). In
      patients with colonic carcinomas (n = 10), the amount of total PK-C activity was
      also decreased (198 pmol/min/mg protein) when compared to adjacent mucosa or to
      the control group (P less than 0.05). In addition, the amount of membrane
      associated PK-C activity (89.1 pmol/min/mg protein) was significantly reduced in
      carcinoma when compared to adjacent mucosa (P less than 0.05). The ratio of
      membrane-associated/total PK-C was not altered in adenomas, while in patients
      bearing carcinomas the relative fraction of membrane-associated PK-C activity was
      increased in samples from carcinomas and equally from adjacent colonic mucosa
      (45.0 and 44.6 versus 28.9%, P less than 0.05) when compared to controls. These
      results indicate that alterations within the protein kinase C pathway occur as
      early events in the adenoma-carcinoma sequence of intestinal mucosa, suggesting
      an important role of PK-C in epithelial differentiation and growth.

PMID- 1988086
TI  - Preclinical in vivo activity of 2',2'-difluorodeoxycytidine (Gemcitabine) against
      human head and neck cancer.
AB  - 2',2'-Difluorodeoxycytidine (dFdCyd, Gemcitabine) is a new deoxycytidine analogue
      with striking preclinical antitumor activity in solid tumors from murine and
      human origin. In this study, dFdCyd was tested for its antitumor effect in human
      tumor xenografts derived from squamous cell carcinoma of the head and neck
      (SCCHN). NMRI nude mice bearing s.c. growing tumors with a volume of 50 to 150
      mm3 were given i.p. injections of a maximum tolerated dose of 120 mg/kg dFdCyd,
      every 3 days for four injections. A significant antitumor effect was observed in
      all five tested SCCHN tumor lines; in four of these lines the median tumor volume
      doubling time increased more than a 3-fold upon dFdCyd treatment. In two lines
      dFdCyd was curative (no tumor regrowth 90 days after treatment) in one of six and
      two of eight xenografts, respectively. Schedule dependency was investigated in
      three SCCHN lines, showing, in the two most sensitive lines, that treatment with
      a 3-day interval was superior to the schedules with daily or weekly injections.
      At equitoxic doses, dFdCyd was more active in this model than the drugs that are
      clinically used in SCCHN, i.e., cisplatin, methotrexate, 5-fluorouracil, and
      cyclophosphamide. dFdCyd is a good candidate for clinical trials with SCCHN
      patients.

PMID- 1988087
TI  - Preclinical assessments of 90Y-labeled C110 anti-carcinoembryonic antigen
      immunotoxin: a therapeutic immunoconjugate for human colon cancer.
AB  - We have synthesized 90Y-labeled immunotoxin (IT) containing ricin A chain and
      C110 anti-carcinoembryonic antigen monoclonal antibody (MAb) to produce a
      therapeutic immunoconjugate for human colon cancer. The C110 IT was labeled with
      90Y via a benzylisothiocyanate derivative of diethylenetriaminepentaacetic acid.
      The efficiency of 90Y labeling was consistently 90 to 98%, with a specific
      activity of about 1 microCi/microgram. In in vitro stability studies, more than
      80% of 90Y remained bound to the C110 IT for up to 5 days after incubation. The
      percentage of binding of 90Y-labeled C110 IT to carcinoembryonic antigen-coated
      microbeads was 86%, indicating good retention of the initial immunoreactivity of
      the C110 MAb. In in vitro protein synthesis inhibition assays, 90Y-labeled C110
      IT was approximately 3.7-fold more toxic to the LS174T human colon carcinoma cell
      line than unmodified C110 IT and 1380-fold more toxic than 90Y-labeled C110 MAb.
      Biodistribution studies of 90Y-labeled C110 IT in LS174T tumor-bearing mice
      showed that, at 24 h following i.p. injection, high accumulation of radioactivity
      was seen in the i.p. tumor and liver and, thereafter, high accumulation in these
      tissues remained almost unchanged until up to 168 h, with percentage of injected
      dose/g ranging from 15 to 18% in the tumor and 10 to 15% in the liver. The
      radioactivity in the spleen and bone gradually increased with time and reached
      their highest levels (approximately 8% of injected dose/g) at 168 h. Estimation
      of absorbed radiation doses to the tissues showed that i.p. tumor would have
      received an approximately 1.5 to 7 times higher radiation dose than normal
      organs. In in vivo therapeutic trials, 90Y-labeled C110 IT provided survival
      prolongation of LS174T tumor-bearing mice superior to that with either unmodified
      C110 IT or 90Y-labeled C110 MAb (4 less than 0.01; Mann-Whitney U test). These
      results indicate that 90Y-labeled C110 anti-carcinoembryonic antigen IT may be a
      potent therapeutic immunoconjugate for human colon cancer and that it may have
      direct relevance for i.p. treatment of peritoneal carcinomatosis from colon
      cancers.

PMID- 1988088
TI  - Microvascular architecture in a mammary carcinoma: branching patterns and vessel
      dimensions.
AB  - The objective of this work was to introduce a tumor vessel classification scheme
      and to provide the first quantitative measurements of vessel branching patterns
      and the related vascular dimensions in a mammary carcinoma. Mammary
      adenocarcinoma R3230AC tumors, grown in the rat ovarian tissue-isolated tumor
      preparation, were infused with Batson's No. 17 polymer and maintained at an
      intravascular pressure of 50 mm Hg during polymerization. Maceration of the tumor
      in KOH allowed visualization of the vasculature. The vessel branching patterns,
      lengths, and diameters were measured in four tumors (4-5 g). A centrifugal
      ordering scheme was devised specifically to account for the unique features of
      tumor microvascular network topology. The arterial networks revealed two types of
      branching patterns. One type of arteriolar network exhibited decreasing vessel
      diameters and lengths with increasing branch order. In a second type of network,
      the diameter and length of the vessels displayed fluctuations in both variables
      at higher generations. Avascular and poorly vascularized regions with sparse
      capillary supply were present in the tumors, but analysis of several capillary
      networks in vascularized regions revealed a nonplanar meshwork of interconnected
      vessels. The meshworks were composed of vessels with a mean segment length of 67
      microns, a mean diameter of 10 microns, and a mean intercapillary distance of 49
      microns. Capillary path lengths ranged from 0.5 to 1.5 mm. Thus, tumor capillary
      diameter was greater than that in most normal tissues and, in the regions where
      capillary networks existed, intercapillary spacing was in the normal range. In
      the venous network, diameters decreased from 650 to 20 microns for the first to
      ninth order venules. Venule length decreased from 5 to 0.5 mm for first to fourth
      order but was fairly uniform (less than 500 microns) for higher orders. In
      conclusion, solid tumor vascular architecture, while exhibiting several features
      that are similar to those observed in normal tissues, has others that are not
      commonly seen in normal tissues. These features of the tumor microcirculation may
      lead to heterogeneous local hematocrits, oxygen tensions, and drug
      concentrations, thus reducing the efficacy of present day cancer therapies.

PMID- 1988090
TI  - Karyotypic changes associated with loss of prolactin dependency of rat Nb2 node
      lymphoma cell cultures.
AB  - The parent line of cultured "Nb2 node" lymphoma cells is dependent on the hormone
      prolactin (PRL) for growth and is widely used for the in vitro bioassay of
      lactogenic hormones. As reported previously, PRL-independent sublines have been
      developed in vitro from the parental line by lactogen deprivation. The present
      study describes the G-banded karyotypes of the Noble (Nb) strain of rat (in which
      the original lymphoma developed), the PRL-dependent cell line (157th generation),
      and two of its PRL-independent sublines (1220th and 2372nd generations). The
      karyotype of the Nb rat was determined to be the same as that of Rattus
      norvegicus. The stemline karyotype of the PRL-dependent cells contains a number
      of well-defined chromosomal abnormalities. The PRL-independent sublines examined
      have the same chromosomal abnormalities as the PRL-dependent cells plus a few
      additional changes indicative of clonal evolution from the PRL-dependent
      stemline. The development of PRL independence (as seen in the 1220th generation)
      was associated with only two karyotypic changes, i.e., loss of the Y chromosome
      and a translocation involving chromosomes 14 and 17. The recently reported
      mapping of the rat PRL gene and other PRL-related genes to chromosome 17 suggests
      that rearrangement of chromosome 17 could be involved in the development of the
      PRL independence. The PRL-dependent and PRL-independent Nb2 cell lines provide a
      useful system for studying chromosomal and molecular genetic events associated
      with the malignant progression of polypeptide hormone-dependent cancers.

PMID- 1988089
TI  - Inhibition of urokinase-type plasminogen activator by antibodies: the effect on
      dissemination of a human tumor in the nude mouse.
AB  - Nude mice given inoculations s.c. of a human squamous carcinoma--HEp3 (1.5 x
      10(6) cells/mouse)--developed invasive tumors that produced high levels of
      urokinase-type plasminogen activator (uPA) and metastasized predictably to the
      lungs and lymph nodes of the host. To investigate the role of uPA in invasion and
      metastasis, mice given inoculations of tumor cells were treated daily with s.c.
      injections of specific, anti-human uPA antibodies (rabbit polyclonal, 150
      inhibitory units; mouse monoclonal, 3000 inhibitory units/mouse/day). Control
      mice received either saline or preimmune rabbit immunoglobulins. A total of
      approximately 50 mice was studied. The tumors were surgically excised 10 to 17
      days postinoculation when weighing 1 to 2 g. Antibody administration was
      discontinued after tumor excision. Two strategies were used: (a) following the
      removal of tumors the mice were maintained and observed until respiratory
      distress, indicative of lung metastasis, was evident; or (b) their lungs were
      examined for evidence of metastasis on the day of tumor removal. While
      histological sections of s.c. tumors excised from control mice indicated
      extensive local invasion, evidence of invasion was absent in most tumors excised
      from mice in which tumor uPA was inhibited by the antibody (P less than 0.025).
      The inhibition of local invasion did not, however, lead to a reduced incidence of
      distant metastasis. Since we found that the presence of HEp3 tumors in mice
      elicits a pronounced granulocytosis, we propose that this response may facilitate
      the spread of tumor cells by a mechanism independent of endogenous tumor
      proteases.

PMID- 1988091
TI  - DNA damage induced by 193-nm radiation in mammalian cells.
AB  - The contribution of DNA damage to the effects of 193-nm excimer laser radiation
      on mammalian cells in culture was studied in order to evaluate the mutagenic
      potential of this UV wavelength in vivo. Two approaches were taken: measurement
      of pyrimidine dimer-specific endonuclease-sensitive sites/megabase and comparison
      of the 193-nm radiation-induced cytotoxicity in normal versus DNA repair
      deficient cells. The formation of pyrimidine dimer-specific endonuclease
      sensitive sites/megabase was inversely related to the thickness of the cytoplasm
      overlying the nuclei of normal human fibroblasts (NHF) and Chinese hamster ovary
      cells. The results of these measurements and a calculation of the absorption
      coefficient of cytoplasm indicate that each 1 micron of cytoplasm attenuates the
      incident radiation by greater than 90% and, therefore, the nuclear DNA in tissue
      will be highly protected from 193-nm radiation by overlying cytoplasm. The
      reduction in colony-forming ability induced by 254-nm, 193-nm, and X-ray
      radiation was measured in NHF, xeroderma pigmentosum (group A) cells, and ataxia
      telangiectasia cells. Xeroderma pigmentosum (group A) cells were 16.5 times more
      sensitive to 254-nm radiation but only 3.5 times more sensitive to 193-nm
      radiation than NHF cells, indicating that cyclobutylpyrimidine dimers were not
      the major lethal lesion formed at 193 nm. AT cells were 3.4 times more sensitive
      to X-rays than NHF cells, but these cell types were almost equally sensitive to
      193-nm radiation, indicating that 193 nm did not induce the same type of lethal
      lesions as X-rays.

PMID- 1988092
TI  - Expression and inducibility of drug-metabolizing enzymes in novel murine liver
      epithelial cell lines and their ability to activate procarcinogens.
AB  - Four novel nontransformed epithelial cell lines, isolated from fetal or adult
      mouse liver, were tested: (a) to determine the profile of xenobiotic metabolizing
      enzymes; (b) to evaluate the inducibility of the polysubstrate (cytochrome P-450
      dependent) monooxygenase system by various classes of inducers; and (c) to assess
      the capacity of the cells to metabolize structurally different procarcinogens.
      With regard to the phase I pathway, the cells expressed various P-450 (class IA,
      IA2, IIB, IIE1, IIIA) and flavin adenine dinucleotide-containing monooxygenase
      dependent bio-transformation enzyme activities at levels (in lines C2.8 and C6)
      comparable with those present in murine adult liver preparations. The expression
      of various P-450s was demonstrated also by immunoprecipitation assays using
      rabbit polyclonal antibodies. For the phase II pathway, cells expressed
      substantial levels of glutathione S-transferase, glutathione S-epoxide
      transferase, and UDP-glucuronosyltransferase. Low expression of epoxide hydrolase
      was observed. Induction of P-450 function by sodium phenobarbital, beta
      naphthoflavone, isosafrole, ethanol, and pregnenolone 16 alpha-carbonitrile,
      monitored using specific P-450-linked activities, was considerably elevated (over
      5-fold in class IIB with the C2.8 and C6 cell lines). The most competent C2.8 and
      C6 cell lines were able to activate benzo(a)pyrene, cyclophosphamide,
      dimethylnitrosamine, diethylstilbestrol, and 2-naphthylamine as shown by the
      significantly increased frequencies of mitotic gene conversion, mitotic crossing
      over, and point [reverse] mutation in the diploid D7 strain of Saccharomyces
      cerevisiae after 4 [cyclophosphamide], 24 [benzo(a)pyrene,2-naphthylamine,
      dimethylnitrosamine] or 48 [diethylstilbestrol], h of exposure in the presence of
      3 x 10(6) cells/flask. The degree of conservation and the inducibility of
      representative oxidative and postoxidative reactions in the novel epithelial cell
      lines C2.8 and C6, together with their ability to activate a wide spectrum of
      procarcinogens, offers a means to study the potential of chemicals for inducing
      DNA damage in short-term genotoxicity testing. In addition the cells may be
      suitable for analyzing the metabolic disposition of compounds and the multistage
      process of carcinogenesis.

PMID- 1988093
TI  - Antitumor activity of idarubicin-monoclonal antibody conjugates in a disseminated
      thymic lymphoma model.
AB  - Many of the experimental approaches used in the search for new targeted drug
      delivery systems ignore the disseminated nature of metastatic disease; the
      development of more relevant tumor models is therefore a priority. A reproducible
      and tumor-specific model has been generated by inoculating (C57BL/6 x BALB/c) F1
      (Ly-2.2+) mice i.v. with the Ly-2.1+ murine ITT(1) 75NS E3 thymic lymphoma (E3).
      At a dose of 2 x 10(6) cells, E3 tumors grew in a disseminated fashion, arising
      initially and predominantly in the lung and kidney, and later and less often in
      the thymus, spleen, and other tissues. In addition, histopathological examination
      and flow cytometry of blood did not detect E3 tumor cells in most other organs or
      in the circulation throughout the course of disease. The mean survival time (MST)
      of untreated mice was both reproducible and proportional to the number of E3
      tumor cells injected and was therefore used to demonstrate the suitability of
      this model for immunochemotherapeutic studies. When examining the antitumor
      efficacy of idarubicin-monoclonal antibody conjugates, it was observed that the
      survival times of treated mice were consistent within groups and between
      experiments. The disseminated E3 (Ly-2.1+) tumor model, like the s.c. E3 tumor
      model, demonstrated the dose-dependent efficacy of idarubicin-anti-Ly-2.1
      conjugate treatment and illustrated both the negligible antitumor activity and
      toxicity of idarubicin alone. Furthermore, lung and kidney weight measurements
      formally demonstrated that the increased MST of treated mice represented a
      reduction of E3 tumor burden in these organs. This model provides a useful tool
      for study of the immunochemotherapy of disseminated tumors in mice and further
      illustrates the antitumor activity of idarubicin-monoclonal antibody conjugates.

PMID- 1988094
TI  - Combined analysis of DNA ploidy index and N-myc genomic content in neuroblastoma.
AB  - The aim of the study was to assess, in a group of nonselected patients with
      neuroblastoma, the prognostic value of both N-myc gene amplification and DNA
      ploidy index, taking into account potential confounding factors such as age and
      stage. Of 59 patients studied, 23 were younger than 1 year at diagnosis, 31
      presented with stage IV, 10 with stage III, 5 with stage II, 8 with stage I, and
      4 with stage IV-S. N-myc genomic content was analyzed by Southern blot
      hybridization technique and N-myc amplification (greater than or equal to 3
      copies/haploid genome) was present in 6 stage IV, 2 stage III, and 1 stage IV-S.
      The DNA ploidy index was analyzed by flow cytometry. Of the 59 neuroblastomas, 26
      were diploid (DNA index, 1) and 33 were aneuploid (DNA index, greater than 1).
      The majority of the aneuploid tumors (28 of 33) were near-triploid with DNA
      indexes between 1.25 and 1.68, 4 were near-diploid (DNA index up to 1.18), and 1
      was hypotetraploid (DNA index, 1.85). The proportion of near-triploid tumors was
      significantly greater among patients under 1 year of age and among patients
      presenting with stages I, II, and IV-S. Interestingly, 0 of 28 near-triploid
      neuroblastomas exhibited N-myc gene amplification, compared to 9 of 31 in the
      group of diploid, near-diploid, and hypotetraploid tumors (Fisher's exact test, P
      less than 0.001). Four factors were significantly related to a high risk of
      relapse in univariate analysis, i.e., age, stage, DNA index, and N-myc
      amplification. In multivariate analysis, only N-myc amplification and the DNA
      index remained significantly associated with a high risk of relapse. The 2-year
      disease-free survival rate was 94% (95% confidence interval, 77-98%) for patients
      with near-triploid neuroblastoma, compared to 45 and 11% (95% confidence
      interval, 32-70 and 4-23%) for patients with diploid or near-diploid tumors,
      without and with N-myc amplification, respectively. We concluded that the
      combination of N-myc and DNA index should be included in routine management of
      neuroblastoma.

PMID- 1988096
TI  - Biochemical and genetic characterization of the HBA71 Ewing's sarcoma cell
      surface antigen.
AB  - Monoclonal antibody HBA71 detects a cell surface antigen of human Ewing's
      sarcomas and peripheral neuroepitheliomas that distinguishes these tumors from
      other small round cell tumors of childhood and adolescence. In the present study,
      we show that monoclonal antibody HBA71 reacts with polypeptides of Mr 32,000 and
      30,000 and that the HBA71-coding gene segregates with human chromosomes X and Y
      in rodent-human hybrids. Therefore, we compared HBA71 to the T-cell leukemia
      antigen 12E7, which is encoded by the pseudoautosomal region of chromosomes X and
      Y. We show that monoclonal antibodies HBA71 and 12E7 (a) detect polypeptides of
      identical size, (b) react with mouse cells transfected with complementary DNA
      corresponding to the 12E7-coding gene, MIC2, and (c) give similar patterns of
      reactivity with human tumor cell lines and small round cell tumor tissues. Thus,
      HBA71 and 12E7 are identical or closely related antigens and the available MIC2
      probes will facilitate analysis of the molecular mechanisms that determine
      differential HBA71 expression in small round cell tumors of childhood and
      adolescence.

PMID- 1988095
TI  - Characterization of mucin antigens recognized by monoclonal antibodies raised
      against human colon cancer cells.
AB  - Two monoclonal antibodies, MLS 102, which recognizes cancer-associated mucin
      antigens, and MLS 103, which recognizes normal mucin, were used to isolate, by
      immunoaffinity chromatography, the corresponding antigens from cell lysates and
      spent medium of a human colorectal carcinoma cell line, LS 180. The MLS 102
      antigen contained serine, threonine, and proline as major amino acids. The
      carbohydrate chains of the MLS 102 antigen were composed of O-linked NeuAc alpha
      2----6GalNAc (56%), N-acetylgalactosamine (25%), and longer oligosaccharide
      chains. The MLS 103 antigen differed from the MLS 102 antigen in both amino acid
      and carbohydrate composition. Most O-linked oligosaccharides of the MLS 103
      antigen were longer than the disaccharide found in the MLS 102 antigen.
      Immunostaining of LS 180 cells using MLS 102 and MLS 103 revealed that the cells
      are heterogeneous with respect to the expression of the antigens.

PMID- 1988097
TI  - Hyperthermia effects on cytosolic [Ca2+]: analysis at the single cell level by
      digitized imaging microscopy and cell survival.
AB  - Digitized video-intensified fluorescence microscopy with the Ca2(+)-sensitive
      fluorescent dye fura-2 was used to measure cytosolic free Ca2+ [( Ca2+]f) in HT
      29 human colon cancer cells. At 37 degrees C, the [Ca2+]f of individual cells
      ranged between 50 and 150 nM, with a mean of 120 nM. Raising the temperature to
      41 degrees C for 1 h resulted in a slight reversible decrease (10-20%) in the
      mean [Ca2+]f. At 44 degrees C for 1 h, most (greater than 80%) cells exhibited a
      [Ca2+]f greater than 200 nM. This heat-induced rise in [Ca2+]f was not immediate
      but commenced after a lag time of 30 min. Postincubation at 37 degrees C for 2-6
      h after heating, for 1 h at 44 degrees C resulted in a recovery of the basal
      [Ca2+]f in some but not all cells. A linear relationship was determined between
      percentage of cell killing and the number of cells with [Ca2+]f of greater than
      200 nM after 37 degrees C post-heating incubation. Manipulation of extracellular
      [Ca2+] between 0.1 and 10 mM during heating did not modify the heat-induced
      changes in [Ca2+]f. No significant differences in survival at 37 degrees C or 44
      degrees C were observed with cells incubated at 10, 1.0, and 0 [plus 1.0 mM
      ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid] mM
      extracellular Ca2+. The Ca2+ channel blockers verapamil and nifedipine did not
      protect cells from heat treatment. These results suggest that irreversible heat
      induced changes in intracellular Ca2+ homeostasis mechanisms may be a critical
      factor in heat cytotoxicity.

PMID- 1988098
TI  - Concentration-dependent increase of murine P388 and B16 population doubling time
      by the acyclic monoterpene geraniol.
AB  - Geraniol, an acyclic end product of a plant isoprene pathway and a
      pyrophosphorylated intermediate in plant and animal pathways, caused a
      concentration-dependent increase in the population doubling time of murine P388
      leukemia cells in suspension culture and of B16 melanoma cells in monolayer
      culture. The suppression of the growth of P388 cells by geraniol (0-0.9 mM) and
      by mevinolin (0-0.25 microM), a competitive inhibitor of mevalonate biosynthesis,
      was reversed by the addition of 0.5 mM mevalonolactone to the growth medium. Flow
      cytometry of asynchronous B16 cells grown with geraniol (0-0.15 mM) revealed a
      population characterized by larger cells with altered nuclear characteristics.
      Over the course of four studies, dietary geraniol increased the 50% survival time
      of mice by 10, 29, 33, and 50% following the i.p. transfer of P388 cells. The
      results of the latter study showed that, following the i.p. transfer of 1 x 10(5)
      P388 cells, the control group of female C57BL x DBA/2 F1 mice had a 50% survival
      time of 24 days and a maximum survival of 27 days. Mice fed a diet containing
      0.1% geraniol for 14 days prior to and following the P388 cell transfer had a 50%
      survival time of 36 days, and 20% of the mice remained free of tumors during the
      50-day trial. These studies support the possibility that monoterpenes and other
      isoprenoid products of plant metabolism are in part responsible for the
      anticarcinogenic actions of diverse fruits, vegetables, and cereal products.

PMID- 1988099
TI  - Increased content of an endogenous lactose-binding lectin in human colorectal
      carcinoma progressed to metastatic stages.
AB  - The quantity and localization of two lactose-binding lectins with molecular
      weights of 31,000 and 14,500 in human colorectal carcinoma tissue specimens
      obtained by surgical resection have been studied using specific polyclonal
      antibodies. Electrophoretic separation and blotting of detergent extracts of
      tumor tissues (48 specimens), followed by the binding of an antibody that
      recognizes both of these lectins, demonstrated that the contents of Mr 31,000 and
      14,500 lectins vary from one specimen to another. The Mr 31,000 lectin content
      was higher in tumor specimens classified as Dukes' stage D than in those from
      other stages. A significant correlation was found between Mr 31,000 lectin levels
      and the levels of carcinoembryonic antigen in the patients' sera at the time of
      surgery. Immunohistochemical staining with antibodies specific for each lectin
      was performed with 20 colon carcinoma tissues and 5 colonic adenoma tissues. The
      results showed that the Mr 31,000 lectin localizes in the cytoplasm of colorectal
      carcinoma cells and normal epithelial cells, whereas antibody binding to Mr
      14,500 lectin is observed in a limited number of carcinoma specimens and is
      mainly associated with luminal surfaces and secretory products. Adenoma cells
      were reactive with Mr 14,500 anti-lectin antibody at their luminal surfaces or
      cytoplasms, but they did not stain with Mr 31,000 anti-lectin antibody. These
      results suggest that a correlation exists among the level of the Mr 31,000
      lectin, the serum level of carcinoembryonic antigen, and the stage of progression
      of colorectal carcinomas.

PMID- 1988100
TI  - Endothelial cell membrane vesicles in the study of organ preference of
      metastasis.
AB  - Many malignancies exhibit distinct patterns of metastasis that appear to be
      mediated by receptor/ligand-like interactions between tumor cells and organ
      specific vascular endothelium. In order to study endothelial cell surface
      molecules involved in the binding of metastatic cells, we developed a perfusion
      method to isolate outside-out membrane vesicles from the lumenal surface of rat
      lung microvascular endothelium. Lungs were perfused in situ for 4 h at 37 degrees
      C with a solution of 100 mM formaldehyde, 2 mM dithiothreitol in phosphate
      buffered saline to induce endothelial cell vesiculation. Radioiodinated rat lung
      endothelial cell membrane vesicles bound lung-metastatic tumor cells (B16F10,
      R323OAC-MET) in significantly higher numbers than their low or nonmetastatic
      counterparts (B16F0, R323OAC-LR). In contrast, leg endothelial membrane vesicle
      showed no binding preference for either cell line. Neuraminidase treatment of
      vesicles abolished specificity of adhesion of lung-derived vesicles to lung
      metastatic tumor cells. These results demonstrate that in situ perfusion is an
      appropriate technique to obtain pure endothelial cell membrane vesicles
      containing functionally active adhesion molecules. The preferential binding of
      lung-derived endothelial cell membrane vesicles by lung metastatic tumor cells is
      evidence of the importance of endothelial cell adhesion molecules in the
      formation of metastases.

PMID- 1988101
TI  - Invasion of reconstituted basement membrane matrix is not correlated to the
      malignant metastatic cell phenotype.
AB  - Interactions between tumor cells and basement membranes represent a critical step
      in the progression of neoplasia and in the metastatic process. Reconstituted
      basement membrane matrix, matrigel, has been recently used with the aim of
      developing an in vitro assay of tumor cell invasiveness. We have extended these
      studies by comparing the invasiveness of a large series of normal and malignant
      epithelial and mesenchymal cells of human and animal origin cultured on matrigel.
      Normal cells (fibroblasts, glomerular mesangial cells, keratinocytes), human
      fibrosarcoma cells (HT1080), and reticular sarcoma cells (M5076) clearly
      established invasive capabilities in the matrix. However, all the other tested
      cell lines, malignant or virally transformed cells invasive in vivo (MCF7, T47D,
      SA52, SW613, MO4, A431, BeWo), as well as normal nontransformed cells (MOH22)
      were incapable of penetration. The morphological features of matrigel invasion by
      normal fibroblasts and HT1080 cells are described at the light and electron
      microscope levels. The extent of degradation of a radiolabeled matrigel is
      minimal and similar in several cell lines reported to be noninvasive or invasive
      in vivo. Our data suggest that matrigel does not provide a universal model to
      correlate the invasiveness of cells in vivo and in vitro.

PMID- 1988102
TI  - Cytogenetic profile of 109 lipomas.
AB  - Cytogenetic analysis of short-term cultures was carried out on 109 lipomas from
      92 patients. Clonal chromosomal abnormalities were present in 50% of the tumors
      analyzed. Based on the results, three main cytogenetic groups were identified and
      included: (a) tumors with normal karyotypes, (b) tumors with abnormalities
      involving region q13-15 on chromosome 12, and (c) tumors with other clonal
      aberrations. Within each of these groups, cytogenetic subgroups could be
      identified, each characterized by a specific anomaly. Tumors with abnormalities
      of 12q included specific subgroups with t/ins(1;12)(p32-33;q13-15), t(2;12)(p21
      22;q13-14), t(3;12)(q28;q14), t(12;21)(q13;q21), complex, and nonrecurrent
      aberrations. The group containing heterogeneous clonal aberrations included
      subgroups with del(13)(q12q22), der(6)(p21-23), der(11)(q13), and nonspecific
      aberrations. Chromosome bands 1p36, 1p32-33, 2p21-22, 3q27-28, 6p21-23, 11q13,
      12q13-15, 13q12, 13q22, 17p13, 17q21, and 21q21-22 were preferentially involved
      in structural rearrangements in lipomas. The identification of these sites of
      nonrandom rearrangements may serve to identify genes (at or near the junctions of
      chromosomal aberrations) involved in normal cellular growth control. Statistical
      analysis of the data revealed a correlation among karyotypic abnormalities and
      clinical data, such as age and sex of the patient, and tumor depth, site, and
      size.

PMID- 1988103
TI  - Some antagonists of platelet activating factor are cytotoxic for human malignant
      cell lines.
AB  - Nine new platelet activating factor (PAF) antagonists from 4 different chemical
      classes (thiopyrimidines: SDZ 59-015; thioimidazolines: SDZ 61-813;
      imidazoisoquinolines: SDZ 62-434, SDZ 62-759, SDZ 63-135, SDZ 63-596; and
      imidazopiperidines: SDZ 61-638, SDZ 62-293, SDZ 62-694) have been tested for
      cytostatic/antiproliferative ([3H]thymidine uptake) and cytotoxic (trypan blue
      dye exclusion) activity in neoplastic human cell lines of different histology in
      vitro. The antiproliferative activity of 3 of the 9 PAF antagonists (SDZ 61-638,
      SDZ 61-813, SDZ 62-694) was not stable after freezing and thawing. SDZ 59-015
      showed only minor cytotoxic or antiproliferative effects in a dose range of 2-40
      microns after 24, 48, and 72 h of incubation. SDZ 62-434 showed varying activity.
      There were no significant differences between the activities of the other 3 PAF
      antagonists from the imidazoisoquinoline class, which showed drug concentrations
      inhibiting 50% of the activity studied (IC50) and drug concentrations yielding a
      50% decrease of trypan blue dye exclusion (LC50) of less than or equal to 20
      microM at greater than or equal to 48 h, even in the K-562 cell line, which is
      known to be rather resistant for a variety of cytotoxic drugs related to PAF. SDZ
      62-293 showed the best antineoplastic properties with IC50 and LC50 values less
      than or equal to 10 microM at greater than or equal to 48 h including K-562. SDZ
      62-434, SDZ 62-759, SDZ 63-135, SDZ 63-596, and SDZ 62-293 have been further
      tested in a human tumor cloning assay in 5 cell lines. Colony formation was
      reproducibly suppressed to less than 30% of the controls only by SDZ 63-135 (less
      than or equal to 40 microM) and SDZ 62-293 (less than or equal to 20 microM)
      during continuous exposure. There was no correlation between the IC50 values for
      the antiproliferative activity of the test compounds and their IC50 values for
      PAF-induced human platelet aggregation. Furthermore, the antiproliferative
      activity of the most active compound, SDZ 62-293, could not be antagonized by
      preincubation with the specific PAF antagonists WEB 2170 or WEB 2086 or PAF
      itself in noncytotoxic doses.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1988105
TI  - Mouse pulmonary carcinogenesis: a symposium to honor the memory of Dr. Michael B.
      Shimkin.

PMID- 1988104
TI  - Identification of a second human nm23 gene, nm23-H2.
AB  - Reduced RNA and/or protein levels corresponding to the murine nm23-1 and human
      nm23-H1 complementary DNA clones have been correlated with high tumor metastatic
      potential in several rodent model systems and human breast carcinomas. We report
      the identification of a second human nm23 gene, designated nm23-H2. The pNM23-H2S
      complementary DNA clone predicted a Mr 17,000 protein 88% identical to nm23-H1.
      nm23-H2 also shared a significant homology with nucleoside diphosphate kinases
      and a Drosophila developmental gene. Southern blots containing BglII-restricted
      genomic DNA, which exhibited an allelic restriction fragment length polymorphism
      for nm23-H1, contained nonallelic bands upon rehybridization to the nm23-H2
      probe. Thus, nm23-H1 and nm23-H2 are distinct genes. Northern blot hybridization
      of nm23-H1- and nm23-H2-specific probes to breast tumors and cell lines indicated
      that nm23-H1 expression was reduced in high metastatic potential tumor cells to a
      greater extent than nm23-H2. The data indicate the existence of a family of
      independently regulated nm23 genes.

PMID- 1988106
TI  - The chemical and biological route from podophyllotoxin glucoside to etoposide:
      ninth Cain memorial Award lecture.

PMID- 1988107
TI  - Participation of T-lymphocytes in the curative effect of a novel synthetic
      polyamine analogue, N,N'-bis[3-(ethylamino)propyl]-1,7-heptanediamine, against
      L1210 leukemia in vivo.
AB  - We have recently established that combination therapy with N,N'-bis[3
      (ethylamino)propyl]-1,7-heptanediamine (BEPH), a synthetic polyamine analogue,
      and N,N'-bis-2,3-butadieneyl-putrescine, a polyamine oxidase inhibitor,
      eradicated L1210 leukemia in mice and induced resistance to a subsequent L1210
      challenge. We now demonstrate that BEPH treatment alone, given on a more frequent
      schedule (5 mg/kg, day 3, 4, 5) or at a higher dose (10 mg/kg, day 3, 4), cures
      100% of L1210 leukemic mice. These treated animals were subsequently immune to a
      second challenge with L1210 tumor cells. However, mice cured with BEPH did not
      reject P388 leukemic cells, although their mean survival time was slightly
      prolonged. In an in vivo tumor neutralization assay, splenocytes from cured mice
      and L1210 cells were injected into naive mice; 80% did not develop L1210
      leukemia. Coculturing lymphocytes from cured mice with L1210 cells in vitro
      generated a potent tumor-specific cytolytic response against L1210 target cells,
      whereas lymphocytes from naive mice did not generate any significant cytolytic
      activity. Both the in vitro and in vivo activities were completely eliminated by
      pretreating the splenic lymphocyte population with anti-Thy-1.2 monoclonal
      antibodies and complement, indicating T-cells as the effector population. In T
      cell-deficient nude mice BEPH treatment was not curative, increasing survival
      time by approximately 2-fold. We conclude from these studies that T-cell-mediated
      immunity plays a pivotal role in the mechanism by which synthetic polyamine
      analogues, such as BEPH, prevent neoplastic growth.

PMID- 1988108
TI  - Effect of buthionine sulfoximine on toxicity of verapamil and doxorubicin to
      multidrug resistant cells and to mice.
AB  - Resistance of tumor cells to chemotherapeutic drugs may be due to several
      mechanisms within a single cell line. Resistance to doxorubicin in the human
      multidrug resistant breast cancer cell line, MCF-7 AdrR, has been attributed to
      increased glutathione (GSH) S-transferase and GSH peroxidase activity, as well as
      to increased expression of the mdr1 gene product, P-glycoprotein. We studied the
      potentiation of doxorubicin activity in these cells by buthionine sulfoximine
      (BSO), a specific inhibitor of gamma-glutamylcysteine synthetase, and by
      verapamil and trans-flupenthixol, agents which interact with P-glycoprotein.
      Treatment with BSO enhanced the effect of doxorubicin by 1.5-fold, while
      verapamil or transflupenthixol caused a greater reversal of drug resistance. The
      combination of BSO with trans-flupenthixol produced no further potentiation of
      doxorubicin activity. However, the combination of BSO with verapamil and
      doxorubicin caused up to a 10-fold increment in antiproliferative effect. To
      explore the mechanism by which BSO interacted with this drug combination, we
      determined whether or not BSO might potentiate the effects of verapamil. These
      studies demonstrated that the effects of BSO were predominantly due to an
      increase in verapamil toxicity rather than to doxorubicin toxicity. In addition,
      when mice received concentrations of BSO in their drinking water sufficient to
      deplete GSH and were treated with verapamil, the calcium channel blocker was
      lethal to 9 of 12 mice receiving BSO compared to 1 of 10 control animals
      receiving verapamil alone. These studies demonstrate that BSO does not markedly
      increase the pharmacological effect of doxorubicin against MCF-7 AdrR cells and
      suggest that alterations in GSH and related enzymes are not a major factor in
      drug resistance in this cell line. Furthermore, BSO can increase the toxicity of
      verapamil, a finding which may have important implications for clinical trials.

PMID- 1988109
TI  - Tumor-dependent increased plasma nitrate concentrations as an indication of the
      antitumor effect of flavone-8-acetic acid and analogues in mice.
AB  - The antitumor agent flavone-8-acetic acid (FAA) is remarkable because it induces
      hemorrhagic necrosis, altered tumor blood flow, and cytokine synthesis. We show
      here that FAA and structurally related analogues increase plasma nitrite plus
      nitrate (NO2-/NO3-) levels in mice. Dose-dependent increases in plasma NO2-/NO3-
      concentrations, which reached maximum levels at 12 h, were found following
      administration of FAA. Furthermore, the presence of a palpable s.c. Colon 38
      tumor significantly enhanced the response. Tumor-dependent increases were also
      observed with the active FAA analogues xanthenone-4-acetic acid, 5-methyl XAA,
      and 5,6-dimethyl XAA, while the inactive analogue 8-methyl XAA failed to increase
      plasma NO2-/NO3- concentrations substantially above basal levels. Increased
      plasma NO2-/NO3- levels were also observed in response to endotoxin (100
      micrograms/mouse) and to recombinant human tumor necrosis factor alpha (4 to 16
      micrograms/mouse). NO2-/NO3- levels may signify nitric oxide production as a
      result of stimulation of the L-arginine-dependent pathway in activated
      macrophages. The tumor dependence of the response may reflect the immunological
      stimulus imposed by tumor implantation. A clear relationship was found between
      increased plasma NO2-/NO3- levels and tumor growth delays induced by FAA and
      xanthenone-4-acetic acid analogues. It is suggested that nitric oxide may
      contribute to tumor cell death by two mechanisms, alteration of blood flow
      contributing to tumor ischemia and direct tumor cell killing. Plasma NO2-/NO3-
      concentrations may be a sensitive indication of the antitumor response to this
      class of compounds.

PMID- 1988111
TI  - Sensitization of human melanoma cells to the cytotoxic effect of melphalan by the
      glutathione transferase inhibitor ethacrynic acid.
AB  - Glutathione transferases are enzymes implied in the resistance of tumor cells to
      bifunctional alkylating cytostatic drugs. We have investigated the effect of the
      glutathione transferase inhibitor by ethacrynic acid on the cytotoxicity of
      melphalan to a human melanoma cell line (RPMI 8322) with a high level of
      glutathione transferase activity. Using 1-chloro-2,4-dinitrobenzene as substrate,
      ethacrynic acid was shown to inhibit the activity of purified human glutathione
      transferases, with 50% inhibition values of 1, 10, and 15 microM for transferase
      mu (class mu), transferase epsilon (class alpha) and transferase pi (class pi),
      respectively, all of which occur in RPMI 8322 cells. Ethacrynic acid at a
      concentration of 20 microM, which by itself was noncytotoxic, increased the
      cytotoxicity of melphalan to RPMI 8322 human melanoma cells approximately 2-fold.
      The induction of DNA interstrand cross-links by 40 microM melphalan was increased
      1.4-fold by 30 microM ethacrynic acid. These results indicate that a potentiation
      of the cytotoxic effect of bifunctional alkylating agents can be achieved by
      inhibition of glutathione transferase and that the enhanced cytotoxicity may be
      caused at least in part by increased formation of drug-DNA adducts.

PMID- 1988110
TI  - Differential activation and inhibition of lymphocyte proliferation by phorbol
      esters, mezerein, teleocidin, and okadaic acid.
AB  - Lymphocytes can be stimulated to proliferate in vitro by mitogens such as
      concanavalin A. The tumor-promoting phorbol ester 12-O-tetradecanoyl phorbol-13
      acetate (TPA) can enhance this proliferation, partly because of an increase in
      interleukin 2 (IL-2) production. However, if lymphocytes are treated with TPA for
      24 h before concanavalin A exposure, IL-2 production and proliferation are
      depressed. The target of the action of TPA is protein kinase C, which is
      activated after a short exposure but down-regulated after a longer one. This
      study was designed to determine if the modulation of IL-2 was separable from the
      modulation of protein kinase C. When phorbol esters phorbol 12-retinoate-13
      acetate, phorbol 12,13-dibutyrate, 12-deoxyphorbol 13-phenylacetate, and 12
      deoxyphorbol 13-phenylacetate-20-acetate, as well as nonphorbol tumor promoters
      mezerein, telocidin, and okadaic acid, were tested, all but okadaic acid
      reproduced the effects of TPA. However, 12-deoxyphorbol 13-phenylacetate and 12
      deoxyphorbol 13-phenylacetate-20-acetate were required at nearly 100-fold higher
      concentrations than TPA to suppress IL-2 production, suppress mitogenesis, and
      cause down-regulation of protein kinase C. A comparison of structures indicated
      that an R group at the 12-position was less important for IL-2 production and
      mitogenesis than for down-regulation of protein kinase C and the suppression of
      mitogenesis. In no case was the modulation of protein kinase C separated from the
      effects on IL-2 production and proliferation.

PMID- 1988112
TI  - Effect of interclonal heterogeneity on the progressive, confluence-mediated
      acquisition of the focus-forming phenotype in NIH-3T3 populations.
AB  - Confluence is an agent that promotes the progressive acquisition of the focus
      forming phenotype in clones of cells within NIH-3T3 populations. This conclusion
      is based on four results. (a) Even in cultures which have been confluent for more
      than 2 weeks without making foci, some cells in those cultures have been affected
      by the confluent state and will make foci if replated and allowed to grow into
      new saturated cultures. Because replicate dishes are very similar in the number
      and type of foci formed after replating, we conclude that the progression toward
      focus formation is substantially completed before replating, while the cells are
      in their original confluent cultures. (b) Different NIH-3T3 populations were
      produced by expansion of small or large numbers of starting cells. When plated
      without exposure to confluence there was little difference in focus production
      among cells from these different sized starter populations. However, confluence
      caused foci to arise more frequently in platings of 10(5) cells derived from
      large starting numbers than from platings of 10(5) cells derived from small
      starting numbers of cells. This implies that the confluent state successfully
      promotes the acquisition of the focus forming phenotype in a limited percentage
      of cells in an NIH-3T3 culture and that those cells are absent from many small
      starting populations. (c) There is a progressive temporal effect of the confluent
      state on focus formation; the number and density of foci that emerge from
      replated confluent cultures increase with the length of time the cells spend in
      the confluent state. (d) There is heterogeneity among different batches of NIH
      3T3 cells in the ability of the confluent state to induce acquisition of the
      focus forming phenotype. Also, the morphology of the foci that do arise after
      confluent treatment differs substantially among cell populations. Nonetheless,
      the foci formed from a single batch of cells are typically similar in morphology,
      indicating that those foci arose from one clone, or very few clones, of cells.

PMID- 1988113
TI  - Relationship of pancreatic cancer apomucin to mammary and intestinal apomucins.
AB  - Pancreatic cancer mucins have several carbohydrate antigens that are potentially
      useful in the detection of pancreatic cancers, but little is known about the core
      polypeptides of pancreatic cancer mucins. In this study, purified mucin from
      SW1990 pancreatic cancer xenografts was deglycosylated by treatment with hydrogen
      fluoride to give pancreatic cancer apomucin. Consistent with near-complete
      removal of carbohydrate, the apomucin had 10- to 70-fold decreased binding of
      lectins and, unlike the native mucin, served as an acceptor for polypeptidyl N
      acetylgalactosaminyl transferase. Antibodies prepared against the apomucin did
      not bind to native mucin, and antibodies that bound to native mucin did not bind
      to apomucin. On the basis of cross-reaction with deglycosylated colon cancer
      mucin and intestinal mucin repeat peptide, apomucins from SW1990 pancreatic
      cancer xenografts contain the intestinal mucin repeat peptide. On the basis of
      binding of breast cancer-reactive monoclonal antibodies 139H2, DF3, and HMFG-2,
      apomucins from SW1990 pancreatic cancer xenografts also have the mammary mucin
      repeat peptide. Using complementary DNA probes specific for intestinal mucin and
      breast mucin sequences, both types of apomucin mRNA were detected in nude mouse
      xenografts of SW1990 cells. In immunohistochemical staining, antibody against
      deglycosylated SW1990 mucin stained normal breast and pancreas but not normal
      colon. Some pancreatic and mammary cancers and most colonic cancers, however,
      were stained by antibodies against both intestinal apomucin and mammary apomucin.
      We conclude that pancreatic cancers can produce mucins with the intestinal repeat
      peptide as well as those with mammary repeat peptide sequences.

PMID- 1988114
TI  - Training in clinical research in oncology.

PMID- 1988115
TI  - Tumor transplantation and tumor immunity: a personal view.

PMID- 1988116
TI  - Induction of in vitro differentiation of mouse erythroleukemia cells by
      genistein, an inhibitor of tyrosine protein kinases.
AB  - We have found that genistein, a specific inhibitor of tyrosine protein kinases,
      induces in vitro erythroid differentiation of mouse erythroleukemia cells.
      Characterization of the induction process indicated that the genistein-induced
      differentiation is different from that induced by conventional inducing agents
      such as dimethyl sulfoxide or hexamethylene-bisacetamide. This conclusion was
      based upon the earlier appearance of differentiated cells, insensitivity to a
      specific inhibitor (dexamethasone), and responsiveness of some of the
      differentiation-resistant cells to genistein in the genistein-induced erythroid
      differentiation. Possible biological significance of this finding is discussed
      with respect to the involvement of protein phosphorylation (or dephosphorylation)
      in mouse erythroleukemia cell differentiation.

PMID- 1988117
TI  - Lonidamine as a modulator of alkylating agent activity in vitro and in vivo.
AB  - We are searching for relatively nontoxic compounds that can positively modulate
      the efficacy of antitumor alkylating agents. Lonidamine inhibits cellular energy
      metabolism and could potentially increase damage by alkylating agents if cellular
      defenses are energy requiring. Exposure of cells to lonidamine (500 microM) for 2
      h under hypoxic conditions followed by 1-h exposures to lonidamine plus
      alkylating agents under normally oxygenated conditions in vitro significantly
      increased the cell kill achieved by cis-diamminedichloroplatinum(II) (CDDP)
      approximately 5-fold and by D-tetraplatin approximately 10-fold at 90% inhibitory
      concentration in MCF-7/CDDP (CDDP-resistant) cells. Carboplatin cytotoxicity,
      however, was little changed. In the MCF-7 parent cell line, treatment with
      lonidamine increased CDDP cytotoxicity by approximately 10-fold, D-tetraplatin by
      approximately 10-fold, and carboplatin by approximately 8-fold at the 90%
      inhibitory concentration. For L-phenylalanine mustard (melphalan), N,N',N"
      triethylenethiophosphoramide (thiotepa), and N,N'-bis(2-chloroethyl)-N
      nitrosourea, little resistance was evident in the MCF-7/CDDP lines compared with
      the parent line. Treatment with lonidamine increased the cytotoxicity of each
      drug by 1.5- to 3-fold in both cell lines. When exposure to lonidamine was
      extended to 24 h before and 12 h after drug exposure in MCF-7 normally oxygenated
      cultures, CDDP (250 microM) cytotoxicity was increased by approximately 100-fold,
      but melphalan cytotoxicity was increased only 2- to 3-fold over the concentration
      range tested. In the FSaIIC murine fibrosarcoma tumor system, five i.p.
      injections of 50 mg/kg of lonidamine over 36 h increased the tumor cell kill by
      CDDP and carboplatin approximately 2- to 3-fold over the dose range tested when
      the platinum complexes were given i.p. immediately after the third lonidamine
      injection. When cyclophosphamide and thiotepa were given in the same schedule, 10
      fold increases in tumor cell killing were evident on tumor excision assay over
      the dosage ranges. The increase in bone marrow toxicity caused by lonidamine in
      addition to the alkylating agents was less than for tumor cells. Finally, in the
      EMT6 murine mammary carcinoma, use of lonidamine at 500 mg/kg twice daily along
      with CDDP, carboplatin, thiotepa, and cyclophosphamide significantly increased
      tumor growth delays by approximately 1.6- to 3.0-fold. The results suggest that
      lonidamine can positively modulate antitumor alkylating agent cytotoxicity and
      may be a clinically useful adjunctive therapy with these drugs.

PMID- 1988118
TI  - Enhancement by methionine enkephalin of colon carcinogenesis induced by
      azoxymethane.
AB  - The effect of the opioid receptor agonist methionine enkephalin (Met-enkephalin)
      and the opioid receptor antagonist naloxone on colonic carcinogenesis induced by
      azoxymethane was investigated in Wistar rats. Rats received ten weekly injections
      of 7.4 mg/kg of body weight of azoxymethane and injections of Met-enkephalin (50
      micrograms/kg of body weight), naloxone (2 mg/kg of body weight), or Met
      enkephalin (50 micrograms/kg of body weight) plus naloxone (2 mg/kg of body
      weight) once every 2 days. In wk 40, the group treated with Met-enkephalin had a
      significantly increased incidence of colonic tumors. A combination of Met
      enkephalin and naloxone attenuated the enhancing effect by Met-enkephalin on the
      development of colonic tumors. Administration of naloxone alone had no influence
      on colonic tumorigenesis. During and after administration of the carcinogen, the
      bromodeoxyuridine-labeling indices of the colon mucosa and/or cancers were
      significantly increased in rats treated with Met-enkephalin. However, a
      combination of Met-enkephalin and naloxone significantly decreased the labeling
      indices of the colon mucosa and/or cancers. These findings indicate that Met
      enkephalin enhanced colon carcinogenesis and that naloxone attenuated this
      enhancement. Because naloxone is an opioid receptor antagonist, these findings
      also indicate that the enhancing effect of Met-enkephalin on colon carcinogenesis
      may be mediated through opioid receptors.

PMID- 1988119
TI  - Role of folylpolyglutamates in biochemical modulation of fluoropyrimidines by
      leucovorin.
AB  - The growth-inhibitory effect of fluoropyrimidines combined with a short-term
      exposure to leucovorin and the pattern of polyglutamylation of folates were
      compared between parental CCRF-CEM cells and a cell line with impaired ability to
      form polyglutamates (CCRF-CEM/P). The combination of leucovorin with 5
      fluorouracil or 5-fluorodeoxyuridine increased the growth inhibition of CCRF-CEM
      cells compared to the fluoropyrimidine alone in the parent cell line but not in
      CCRF-CEM/P cells. In addition, leucovorin produced a significant increase in the
      inhibition of intracellular thymidylate synthase activity caused by 5
      fluorouracil or 5-fluorodeoxyuridine as compared to these drugs alone in CCRF-CEM
      cells, but no increase in inhibition over that produced by the single drugs alone
      was observed in CCRF-CEM/P cells. Although levels of 5,10-methylene
      tetrahydrofolate after leucovorin administration were similar in both cell lines,
      polyglutamylation of this coenzyme was decreased in the CCRF-CEM/P cell line. The
      inability of CCRF-CEM/P cells to form significant levels of polyglutamates of
      N5,N10-methylenete-trahydrofolate, may be responsible for the lack of enhanced
      cell kill observed when a short exposure to leucovorin is used with
      fluoropyrimidines.

PMID- 1988120
TI  - Multiparametric flow cytometry of the modulation of tumor cell membrane
      permeability by developmental antitumor ether lipid SRI 62-834 in EMT6 mouse
      mammary tumor and HL-60 human promyelocytic leukemia cells.
AB  - (+-)-2-[Hydroxy[tetrahydro-2-(octadecyloxy)methylfuran-2-
      yl]methoxyl]phosphinyloxy-N,N,N-trimethylethaniminium hydroxide, inner salt (SRI
      62-834) is a tetrahydrofuran analogue of platelet activating factor (PAF) that is
      currently entering clinical trial. Like other ether lipids it is of interest as a
      membrane-active antitumor agent. Here, we have used two-color multiparameter flow
      cytometry to study simultaneously its effects on cell membrane permeability,
      intracellular pH, and cell size/structure of EMT6 mouse mammary tumor cells and
      HL-60 human promyelocytic leukemia cells in vitro. Concentrations as low as 1
      microM up to 100 microM SRI 62-834 caused a rapid, dose-dependent increase in
      membrane permeability, initially towards outward efflux of the preloaded
      fluorescein probe bis(carboxyethyl)carboxyfluorescein (green fluorescence) and
      then towards influx of extracellular propidium (red fluorescence). At the same
      time, median cell size from light scatter was reduced with an increased
      coefficient of variation, and the proportion of cell debris was elevated. In
      vitro antitumor activity was seen over the same concentration range, as measured
      by tetrazolium dye reduction and cell growth curves. Neither low concentrations
      of PAF (50 nM) nor the potent PAF antagonist 3-[4-(2-chlorophenyl)-9-methyl-6H
      thieno[3,2-f][1,2,4]tria- zolo[4,3a][1,4]diazepin-2-yl]-1-(4-morpholinyl)-1
      propanone (0.5-100 microM) had any influence on the membrane effects of SRI 62
      834, and at higher concentrations (1-200 microM) PAF mimicked the behavior of SRI
      62-834. In addition, the PAF antagonist did not modulate the cytotoxicity of SRI
      62-834 or PAF. HL-60 cells were more sensitive to SRI 62-834 than were EMT6 cells
      in terms of both cytotoxicity and membrane permeability. However, PAF was more
      potent than SRI 62-834 in causing membrane permeabilization with both cell lines,
      whereas PAF was less active than SRI 62-834 in cytotoxicity assays. The results
      support a membrane-damaging role in the cytotoxicity of SRI 62-834 but suggest
      that additional factors are also involved. Membrane permeabilization may be
      related to its reported effects on protein kinase C-dependent intracellular
      calcium signaling but apparently does not involve a conventional PAF receptor in
      HL-60 or EMT6 cells.

PMID- 1988121
TI  - Effects of phenolic antioxidants in low dose combination on forestomach
      carcinogenesis in rats pretreated with N-methyl-N'-nitro-N-nitrosoguanidine.
AB  - The combined effects of low doses of promoters or carcinogens on two-stage
      forestomach carcinogenesis were examined in rats pretreated with N-methyl-N'
      nitro-N-nitrosoguanidine. Groups of 15 rats were given a single 150 mg/kg body
      weight intragastric dose of N-methyl-N'-nitro-N-nitrosoguanidine. Starting 1 week
      later they were fed a diet containing low doses of known forestomach
      promoters/carcinogens (0.5% caffeic acid, 0.2% catechol, 0.5% butylated
      hydroxyanisole, or 0.25% 2-tert-butyl-4-methylphenol), alone or in combination,
      or basal diet without antioxidant supplement for 35 weeks. Histopathological
      examination revealed the incidences of forestomach squamous cell carcinomas in
      animals treated with N-methyl-N'-nitro-N-nitrosoguanidine followed by caffeic
      acid, catechol, butylated hydroxyanisole, 2-tert-butyl-4-methylphenol, and basal
      diet to be 27, 20, 13, 13, and 7%, respectively, whereas the incidence increased
      to 80% by the combined treatment with these four chemicals. The present results
      thus show that although the low doses of individual promoters/carcinogens did not
      have significant promoting activity, their combination exerted a strong enhancing
      influence on rat forestomach carcinogenesis. The findings indicate the importance
      of summation and synergism at a low dose for agents present in the human
      environment.

PMID- 1988122
TI  - Plasma homocysteine in children with acute lymphoblastic leukemia: changes during
      a chemotherapeutic regimen including methotrexate.
AB  - Plasma homocysteine was determined in 12 children with acute lymphoblastic
      leukemia. The patients were investigated prior to chemotherapy (stage I), during
      seven weeks of induction chemotherapy (stage II), and thereafter during
      intermittent high-dose methotrexate (HD-MTX) therapy (stage III). The patients
      were followed for a period of three to 15 months, and the study included a total
      of 80 HD-MTX courses. Before start of chemotherapy (stage I), the average plasma
      homocysteine level in the children with leukemia was 13.18 +/- 6.23 (SD)
      mumol/liter, which is significantly (P less than 0.001) higher than the level in
      control children (6.52 +/- 1.21 mumol/liter). The plasma homocysteine level in
      the patients was positively correlated with the peripheral white blood cell count
      (P less than 0.01) and negatively correlated with serum folate (P less than
      0.02). The serum folate was normal or subnormal in these patients. During
      induction therapy with cytotoxic drugs such as vincristine, asparaginase, and
      intrathecal MTX (stage II), there was a drastic change in plasma homocysteine as
      a function of time. A reciprocal alteration in serum folate was observed,
      suggesting fluctuating intracellular folate status at this stage of therapy. At
      the end of stage II (about seven weeks), there was a significant (P less than
      0.01) reduction in total homocysteine (to 7.08 +/- 3.84 mumol/liter). HD-MTX (8
      g/m2) therapy with 5-formyltetrahydrofolate "rescue" (stage III) was usually
      begun about seven weeks after start of chemotherapy, and the patients were
      followed for two to eight courses separated by three to eight weeks. Plasma
      homocysteine showed a transient increase (26-64%) following each MTX infusion.
      After three MTX infusions, basal total plasma homocysteine was reduced to 5.56 +/
      1.12 mumol/liter. During most MTX infusions, there was a variable reduction (17
      56%) in plasma methionine followed by a rebound increase. It is concluded that
      plasma homocysteine in children with acute lymphoblastic leukemia is elevated
      prior to therapy, probably because of occasional folate deficiency and increased
      burden of proliferating cells. During induction therapy, monitoring plasma
      homocysteine and serum folate both suggest a labile folate homeostasis, usually a
      deficiency state. HD-MTX induced a temporary intracellular folate depletion
      before 5-formyl-tetrahydrofolate was administered, as judged by a transient
      homocysteinemia. The methionine depletion may interfere with the antileukemic
      effect of MTX.

PMID- 1988123
TI  - Phase I trial of natural human interferon beta in metastatic malignancy.
AB  - A phase I trial of natural human beta-interferon (nHuIFN-beta) was initiated to
      evaluate its biological activity, maximum tolerated dose, and toxicity in
      patients with refractory malignancies. nHuIFN-beta was administered to successive
      groups of 4-6 patients as an i.v. bolus on days 1 and 4, for 4 consecutive weeks.
      Dose levels were 0.1, 1.0, 10, 30, 60, 100, and 200 x 10(6) units/m2. Thirty-five
      patients were entered, and 34 patients were evaluable for toxicity,
      immunomodulatory, and antitumor effects. Toxicity was mild to moderate and
      included fever and chills, fatigue, arthralgias, nausea, transient renal and
      hepatic dysfunction, and leukopenia. No dose-limiting toxicity was observed, and
      no responses were seen. Significant immunological changes included the following:
      an increase in natural killer activity on day 5 when compared to pretreatment
      values (P less than 0.01) and an increase in activated T-cells (CD3+/HLA-DR+)
      with increasing doses of nHuIFN-beta (P less than 0.01). Pharmacokinetic data
      demonstrated a short alpha half-life of 12.1 +/- 2.5 (SE) min and a beta half
      life of 129.7 +/- 14.7 min. Neutralizing serum antibodies were detected in 2 of
      27 patients receiving nHuIFN-beta. In conclusion, toxicity of nHuIFN-beta given
      twice weekly was moderate, and further dose escalation is possible. The
      immunological changes and pharmacokinetic behavior of nHuIFN-beta resemble those
      reported with rHuIFN-beta ser.

PMID- 1988124
TI  - An ex vivo model for the study of tumor metabolism by nuclear magnetic resonance:
      characterization of the phosphorus-31 spectrum of the isolated perfused Morris
      hepatoma 7777.
AB  - We have developed an isolated perfused tumor model to study the metabolism of
      solid tumors by nuclear magnetic resonance spectroscopy. Morris hepatomas (7777)
      were implanted in the inguinal region of Buffalo rats, such that they developed
      an isolated blood supply. These tumors were perfused with a RBC perfusate,
      removed from the animal, and studied by 31P nuclear magnetic resonance
      spectroscopy. ATP levels, as determined from the spectra, were stable for as long
      as the tumors were maintained in the magnet (7 h) only if the perfusate contained
      inosine, adenosine, and insulin. The adenosine and inosine were also required for
      recovery from ischemia. Under these conditions, ischemia did not result in a
      change in tumor pH. The gamma nucleoside triphosphate resonance was significantly
      larger than the beta nucleoside triphosphate resonance in spectra of some of the
      perfused tumors, suggesting that ADP above about 300 nmol/g wet weight was not
      complexed in these tumors. The adenylate levels determined from extracts, O2
      consumption, histology, and 31P nuclear magnetic resonance spectra of extracts of
      perfused tumors and tumors in situ were all similar, indicating the perfused
      tumor is a reasonable model of the tumor in vivo.

PMID- 1988125
TI  - Induction of cytokine messenger RNA and secretion in alveolar macrophages and
      blood monocytes from patients with lung cancer receiving granulocyte-macrophage
      colony-stimulating factor therapy.
AB  - Human granulocyte-macrophage colony-stimulating factor (GM-CSF) promotes the
      proliferation and differentiation of hematopoietic progenitor cells. Although
      preliminary data are available from clinical trials, the effect of GM-CSF on gene
      expression of immunocompetent cells in treated patients has not been studied. We
      previously demonstrated that in vitro treatment with GM-CSF also enhances
      maturation-related anti-tumor activities in mononuclear phagocytes. The purpose
      of the present study was to examine the effects of in vivo recombinant GM-CSF
      therapy on alveolar macrophages and blood monocytes, to determine if these cells
      demonstrated differential expression of cytokine genes, cytokine production, and
      tumoricidal activity. Alveolar macrophages and blood monocytes were isolated from
      13 patients receiving a range of GM-CSF doses (60-250 micrograms/m2/day) by
      continuous infusion over a 2-week period. Both monocytes and macrophages were
      isolated prior to therapy and at day 10 of the infusion. Monocytes, in addition,
      were isolated on day 3 of infusion. Results indicated that GM-CSF therapy
      enhanced expression of tumor necrosis factor, interleukin 1, and interleukin 6
      mRNA in both monocytes and alveolar macrophages. Differential responses, however,
      were observed in cytokine secretion; monocytes demonstrated enhanced secretion of
      all three cytokines by day 3 of treatment, but alveolar macrophages showed only
      enhanced interleukin 6 secretion at day 10. Monocyte tumoricidal activity after
      in vitro lipopolysaccharide stimulation was also significantly elevated by day 3
      of treatment, but at day 10 activity was not statistically different from
      pretreatment values in either monocytes or alveolar macrophages. These data
      indicate that GM-CSF exerts striking time-dependent modulatory effects on gene
      expression and functional activities of monocytes and alveolar macrophages in
      vivo, although the responses of the two cell types differ with respect to
      cytokine secretion.

PMID- 1988127
TI  - In vivo activity of solid phase interleukin 2.
AB  - Interleukin 2 (IL-2) coupled to polystyrene beads to form a solid phase of the
      cytokine was able to increase the cytotoxic activity of rat spleen cells in
      vitro. A single injection of the IL-2 coupled beads into the peritoneal cavities
      of normal rats also resulted in the in vivo activation of cytotoxicity of
      peritoneal exudate cells, whereas a single i.p. injection of the same amount of
      soluble IL-2 was not effective. When IL-2 coupled beads were mixed with
      methylcholanthrene-induced Mc7 or Mc107 sarcoma cells and injected into normal
      syngeneic Wistar rats, the growth of the tumor was suppressed. This effect was
      localized to the site of the injection. The in vivo activities were achieved with
      modest amounts of IL-2, less than has been previously reported to be well
      tolerated in rodents. IL-2 coupled to a solid matrix may be useful for delivering
      increased concentrations of the lymphokine to tumor dominant regions while
      maintaining low systemic levels and thereby increasing the therapeutic index.

PMID- 1988126
TI  - Tumor-induced alterations in tissue lipoprotein lipase activity and mRNA levels.
AB  - To elucidate the mechanisms of hypertriglyceridemia observed in the tumor-bearing
      rat, tissue lipoprotein lipase (LPL) activity and LPL mRNA levels were examined
      in the fed and fasted states at different degrees of tumor burden and after tumor
      removal. LPL activity in the epididymal fat pad and cardiac muscle in the 24-h
      fasted rats was significantly decreased with increasing tumor burden (r = -0.53,
      P less than 0.05 and r = -0.72, P less than 0.01, respectively). Tumor removal
      completely reversed these changes. In contrast, no change in LPL activity was
      detected in the fed state since food intake stimulated LPL activity to the same
      extent in both tumor-bearing (TBR) and control rats. LPL activity in the
      diaphragm and skeletal muscle was only marginally altered in TBR, as compared to
      controls. LPL mRNA from the epididymal fat pad and cardiac muscle migrated to the
      same site on agarose gel and hybridized to a LPL-specific complementary DNA
      probe. The decline in LPL activity in epididymal fat pad observed in TBR was
      associated with a decrease in LPL mRNA levels. In contrast, there was no
      significant difference in LPL mRNA levels in cardiac muscle between the two
      groups despite significantly suppressed enzyme activity in tumor bearers. This
      study provides evidence that hypertriglyceridemia in TBR is due in part to tumor
      dependent suppression of adipose and cardiac LPL activity in the fasted state,
      which is stimulated by the presence of tumor. Unlike cardiac LPL, the tumor
      induced changes in adipose LPL activity are regulated at the mRNA level in this
      tumor model.

PMID- 1988128
TI  - Effects of indomethacin, cytokines, and cyclosporin A on tumor growth and the
      subsequent development of cancer cachexia.
AB  - C57BL/6J mice bearing a low or undifferentiated rapidly growing tumor were
      treated daily with either i.p. injections of the recombinant cytokines
      interleukin(IL)-1 alpha, IL-1 beta (21 ng/g), and tumor necrosis factor alpha (21
      ng/g) or s.c. injections of cyclosporin A (60 micrograms/g) or indomethacin (1
      micrograms/g). In some experiments, indomethacin was administered in the drinking
      water corresponding to the amount of s.c. injections. Survival and the time
      course of tumor growth and food and water intake were measured. The nutritional
      state (body composition) of the animals was registered at spontaneous death in
      the course of tumor disease. Indomethacin prolonged survival from 14 +/- 1 to 22
      +/- 1 days in tumor-bearing mice when administered either in the drinking water
      or as s.c. injections. This effect, which was due to tumor growth inhibition, was
      equally effective irrespective of whether indomethacin was instituted on Day 1,
      5, 7, or 9 following tumor implantation. Indomethacin did not inhibit tumor cell
      growth in vitro. Indomethacin-treated tumor-bearing mice were also less anorectic
      than untreated tumor-bearing mice, and their nutritional state, particularly lean
      body mass, was significantly improved by indomethacin at doses (1 micrograms/g)
      that did not influence the food intake or body composition in non-tumor-bearing
      mice. At spontaneous death, indomethacin-treated tumor-bearing mice had a
      significantly larger tumor burden when accounting for their degree of
      malnutrition as compared with untreated tumor bearers. Indomethacin did not
      decrease the elevation in hepatic concentrations of RNA seen in response to tumor
      progression. Adherent peritoneal macrophages from tumor-bearing mice had a lower
      prostaglandin E2 synthesis compared with macrophages from non-tumor-bearing
      controls in the basal state (1100 +/- 150 pg/10(6) cells versus 3700 +/- 922
      pg/10(6) cells). Lipopolysaccharide stimulated macrophages from tumor-bearing
      mice to produce significantly more prostaglandin E2 in vitro compared with
      control macrophages (39,500 +/- 4208 pg/10(6) cells versus 12,500 +/- 4330
      pg/10(6) cells).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1988130
TI  - Solutol HS 15, nontoxic polyoxyethylene esters of 12-hydroxystearic acid,
      reverses multidrug resistance.
AB  - A recently developed non-ionic surfactant called Solutol HS 15 (poly-oxyethylene
      esters of 12-hydroxystearic acid), with low toxicity in vivo, was shown to
      reverse completely the multidrug resistance of KB 8-5 and KB 8-5-11 human
      epidermoid carcinoma cells in vitro but did not potentiate drug toxicity in drug
      sensitive KB 3-1 cells. At a concentration of 10% of its own IC50 (mean
      concentration of drug that causes 50% inhibition of cell growth compared to
      controls), Solutol HS 15 produced a 35-, 28-, and 42-fold reduction in the
      resistance of KB 8-5-11 cells to colchicine, vinblastine, and doxorubicin,
      respectively. Solutol HS 15 was relatively much more potent than the prototypic
      reversing agent, verapamil, for reversing colchicine resistance, compared to the
      ability of each agent to reverse colchicine resistance, compared to the ability
      of each agent to reverse vinblastine resistance. Like verapamil, Solutol HS 15
      promoted a 50-fold accumulation of rhodamine 123 in KB 8-5-11 cells, as measured
      by flow cytometry. Also, Solutol HS 15 and verapamil reduced the efflux of
      rhodamine 123 from KB 8-5-11 cells previously loaded with rhodamine 123 to a
      similar low rate. Solutol HS 15 did not affect the transport of alanine or
      glucose into KB 8-5-11 cells, indicating that its effect upon membrane active
      transport is not entirely nonspecific. Considering their different structure and
      different relative potency for reversing colchicine resistance, Solutol HS 15 and
      verapamil probably reverse multidrug resistance by different mechanisms. Solutol
      HS 15 merits consideration as a potential therapeutic agent because of its
      effectiveness for reversing multidrug resistance in vitro and its low toxicity in
      vivo.

PMID- 1988129
TI  - A cyclophosphamide/DNA phosphoester adduct formed in vitro and in vivo.
AB  - The antitumor activity of cyclophosphamide is thought to be due to the alkylating
      activity of phosphoramide mustard, a metabolite of cyclophosphamide. Reaction of
      2'-deoxyguanosine 3'-monophosphate and phosphoramide mustard resulted in the
      formation of several adducts that could be detected by high performance liquid
      chromatography (HPLC). One of these adducts, isolated and purified by HPLC, could
      be detected by 32P postlabeling. This product was identified by UV, nuclear
      magnetic resonance, and mass spectrometry and by acid, base, and enzymatic
      hydrolysis to be 2'-deoxyguanosine 3'-monophosphate 2-(2-hydroxyethyl)aminoethyl
      ester. A combination of HPLC fractionation of digested DNA and 32P postlabeling
      was used to detect this adduct in calf thymus DNA incubated in vitro with
      metabolically activated cyclophosphamide and in DNA from the liver of mice
      treated with cyclophosphamide. In these DNA samples the adduct occurred at a
      level of 1/10(5) and 1/3 x 10(7) nucleotides, respectively.

PMID- 1988131
TI  - Internalization and action of an immunotoxin containing mistletoe lectin A-chain.
AB  - An immunotoxin consisting of the enzymatically active A-chain of mistletoe lectin
      I and a monoclonal antibody against a surface protein on mouse leukemia L1210V
      cells was found to inhibit protein synthesis in these cells as efficiently as the
      native mistletoe toxin. The immunotoxin was somewhat more slowly endocytosed than
      the native toxin, but in both cases the endocytic uptake continued under
      conditions in which uptake from clathrin-coated pits was inhibited by mild
      acidification of the cytosol. This indicates that the toxin and the immunotoxin
      were at least partially internalized by a non-clathrin-dependent uptake mechanism
      and that uptake by this pathway is responsible for most of the toxic effect on
      the cells. The results indicate that efficient immunotoxins can be made with
      antibodies against cell surface epitopes that are endocytosed by a mechanism not
      involving clathrin-coated pits.

PMID- 1988132
TI  - Suppression of experimental lung colonization of a metastatic variant of murine
      colon adenocarcinoma 26 by a monoclonal antibody 8F11 inhibiting tumor cell
      induced platelet aggregation.
AB  - We have previously established and characterized two monoclonal antibodies, 8F11
      and 20A11, that recognize an Mr 44,000 membrane glycoprotein of metastatic murine
      colon 26 cells. Both monoclonal antibodies inhibit platelet aggregation induced
      by the tumor cells in vitro. In this report, the inhibitory effect of 8F11 on
      lung colonization of i.v.-inoculated tumor cells was examined. The i.v.
      administration of 8F11 suppressed lung colonization of NL-17, a highly metastatic
      variant of colon 26. Inhibition of NL-17 lung colonization by 8F11 was dose
      dependent with a maximum of 80% inhibition at a dose of 800 micrograms
      8F11/mouse. 8F11 did not inhibit metastases at doses lower than 100
      micrograms/mouse. Inhibition of pulmonary metastases by 8F11 was greatest when
      the antibody was administered 2 h before tumor inoculation. The effect was
      diminished when the antibody was given 2 h after tumor inoculation. The pulmonary
      retention of i.v.-inoculated radiolabeled NL-17 cells was decreased by 8F11.
      F(ab')2 fragments of 8F11 also effectively inhibited lung colonization by NL-17
      cells, suggesting that mechanisms unrelated to immune-mediated destruction are
      involved. These results indicate that the monoclonal antibody 8F11 suppresses the
      lung colonization of NL-17 cells by interfering with the initial arrest of tumor
      cells in the lung vasculature through the inhibition of tumor cell-platelet
      interaction.

PMID- 1988133
TI  - Characterization of the colorectal carcinoma-associated antigen defined by
      monoclonal antibody D612.
AB  - Monoclonal antibody (MAb) D612 recognizes an antigen expressed on the cell
      surface of normal and malignant gastrointestinal epithelium. It is a murine
      IgG2a/kappa which has been previously shown to mediate killing of human colon
      carcinoma cells using human effector cells (which could be enhanced in the
      presence of interleukin-2). Sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE) analyses of MAb D612 immunoprecipitates of extracts of
      L-[35S]methionine-, L-[3H]leucine-, and D-[3H]glucosamine-labeled human colon
      carcinoma cells showed that the D612 antigen is a Mr 48,000 glycoprotein. Similar
      estimates of molecular mass were obtained from SDS-PAGE analyses of MAb D612
      immuno-precipitates of radioiodinated extracts of surgically resected colon
      carcinoma and adjacent normal colonic mucosa. D612 antigen was not detectable in
      immunoprecipitates of supernatant media from radiolabeled cell cultures,
      suggesting that the antigen is not readily shed from the surface of cultured
      cells. The D612 antigen was shown to be clearly distinct from previously
      described gastrointestinal carcinoma-associated glycoproteins: the D612 antigen
      shows a migration pattern of SDS-PAGE distinct from those of the antigens
      recognized by MAbs KS1/4 and GA733, and reciprocal immunodepletion analyses of D
      [3H]glucosamine-labeled colon carcinoma cells utilizing MAbs D612 and GA733
      revealed no cross-reactivity between these antibodies. Similarly, competitive
      binding studies between MAbs 17-1A and KS1/4 and MAb D612 revealed no similarity
      between the epitopes recognized by MAb D612 and MAbs 17-1A and KS1/4. MAbs D612
      and 17-1A were also titered in immunoperoxidase staining assays on serial frozen
      sections of normal and malignant colon. MAb D612 showed a higher titer of
      immunostaining reactivity with both normal and malignant colon than did MAb 17
      1A. MAb D612 showed roughly equivalent immunostaining titers against normal and
      malignant colon; whereas MAb 17-1A showed higher titer of immunostaining
      reactivity against the normal colon tissue than against the malignant colon. Flow
      cytometric analysis of phosphatidylinositol-specific phospholipase C-treated
      colon carcinoma cells revealed no loss of D612 antigen from the cell surface,
      suggesting that the mechanisms of attachment of the D612 antigen to the cell
      surface does not involve linkage to a phosphatidylinositol glycan.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 1988134
TI  - Phase I clinical investigation of benzisoquinolinedione (amonafide) in adults
      with refractory or relapsed acute leukemia.
AB  - After Phase I studies of benzisoquinolinedione (amonafide) in solid tumors
      identified myelosuppression as the dose-limiting toxicity, we conducted a Phase I
      study in patients with relapsed or refractory acute leukemia to define the
      optimal dose. Amonafide was given i.v. over 2-4 h daily for 5 days. The starting
      dose was 600 mg/m2/day with subsequent escalation to 750, 900, 1100, 1400, and
      1800 mg/m2/day. Thirty-eight courses were administered to 24 patients, of whom 12
      participated in concomitant pharmacological studies. Nausea and vomiting,
      transient orange discoloration of the skin, and tinnitus occurred at all dose
      levels. The latter symptom, along with lightheadedness and flushing, was related
      to infusion duration; this was increased to 4 h with doses greater than or equal
      to 900 mg/m2. The dose-limiting toxicities were mucositis and painful skin
      erythema which occurred in all 4 patients treated with 1800 mg/m2. No remissions
      occurred. Clearing of peripheral blood blasts occurred in 67% of patients treated
      with 1100 mg/m2 and in all patients treated with greater than or equal to 1100
      mg/m2/day. A decrease in marrow leukemic infiltrate (% blasts x % cellularity) to
      less than 10% occurred in 15 and 50% of patients treated at these levels,
      respectively. There were 10 deaths (42%), which were unrelated to dosage. The
      harmonic mean terminal plasma half-life was 4.6 h (range, 2.5-35.5 h). Three
      patients had long drug half-lives of 9.7, 16.4, and 35.5 h and each had initial
      bilirubin levels greater than 1.0 mg/dl. The average urinary excretion of
      amonafide over 5 days was 3.5% of the total dose. This establishes 1100-1400
      mg/m2/day for 5 days as the maximally tolerated dose of amonafide for studies in
      acute leukemia.

PMID- 1988135
TI  - Complementary DNA encoding human colon cancer manganese superoxide dismutase and
      the expression of its gene in human cells.
AB  - Manganese superoxide dismutase (MnSOD) is a member of a family of metalloenzymes
      that catalyze the dismutation of the superoxide anion to H2O2. It has been shown
      that MnSOD activity in tumor cells is lower than that in their normal
      counterparts. To investigate the molecular basis for the reduced level of MnSOD
      activity in human tumor cells, the primary structure of human MnSOD has been
      determined from complementary DNA (cDNA) isolated from a human colon carcinoma
      (HT-29) cDNA library. The sequence of the mature protein is composed of 198 amino
      acids preceded by a 24-amino acid leader peptide. DNA sequence analysis revealed
      that the translated region of the human tumor MnSOD is virtually identical to the
      MnSOD sequence isolated from normal human sources but exhibits differences in
      both the 5'- and 3'-untranslated regions. DNA blot analysis of genomic DNA
      isolated from HT-29, simian virus-transformed human lung fibroblast (SV-40/WI
      38), and parental human lung fibroblast (WI-38) cells showed an identical pattern
      of hybridization to that of MnSOD cDNA. RNA blot analysis revealed that tumor
      cells have lower levels of MnSOD mRNA. However, the half-life of the mRNA was the
      same (approximately 10 h) in tumor and normal cells. Immunological measurement of
      the level of MnSOD in both normal and tumor cells also showed a reduced level of
      MnSOD protein in the tumor cells. These results suggest that the reduced level of
      MnSOD activity observed in human tumor cells is not due to a defect in the
      primary structure of the MnSOD protein, a change in the dosage of the MnSOD gene,
      or a decrease in the stability of MnSOD mRNA in tumor cells but rather is due to
      a defect or defects in the expression of the gene.

PMID- 1988136
TI  - Follow-up study of HER-2/neu amplification in primary breast cancer.
AB  - Amplification of the HER-2/neu oncogene was determined in 362 tumors from
      patients with primary breast cancer (185 node-positive patients and 177 node
      negative patients). The overall amplification rate was 33% (30% for node-negative
      patients; 31% for patients with 1-3 positive nodes; 40% for patients with greater
      than 3 positive nodes). Gene copy number was not associated with axillary lymph
      node status, steroid receptor status, or patient age but was weakly correlated
      with the size of the primary tumor. Amplification of the HER-2/neu gene did not
      correlate with either disease-free or overall survival in univariate or
      multivariate analyses. The results were unambiguously negative for patients with
      node-negative disease. Although the univariate results for node-positive patients
      were marginally significant (P = 0.07), the significance was not retained in
      multivariate analyses. Thus, while HER-2/neu amplification may be biologically
      important in primary breast cancer, it will only be of marginal utility as a
      prognostic factor for predicting clinical outcome.

PMID- 1988137
TI  - Cytogenetic analysis of 33 basal cell carcinomas.
AB  - Cytogenetic analysis of short-term cultures from 33 basal cell carcinomas (BCC),
      a type of neoplasm for which no previous karyological data exist, revealed clonal
      chromosome aberrations, all of them different, in 8 tumors. In 2 cases, 2
      cytogenetically unrelated clones were detected, suggesting a multicellular origin
      in at least a subset of BCC. A remarkably high level of nonclonal structural
      rearrangements, mostly in the form of seemingly balanced translocations, was
      found in 23 tumors; namely, in 6 of 8 BCC with clonal karyotypic abnormalities
      and in 17 of 25 without. It is possible that some of these aberrations represent
      additional neoplastic clones, thus indicating an even higher level of cytogenetic
      heterogeneity in BCC. We think that the most likely interpretation of the results
      is that BCC may have a multicellular origin, reflecting field cancerization of
      the skin. During subsequent tumor development, the selection pressure narrows
      down the number of clones that infiltrate the surrounding tissue. The finding by
      karyotypic analysis of some apparently monoclonal, some polyclonal BCC, may
      reflect that different tumors have been examined at different points in the
      clonal evolution of the neoplastic cells.

PMID- 1988138
TI  - Carcinogen-induced lymphomagenesis in pim-1 transgenic mice: dose dependence and
      involvement of myc and ras.
AB  - Transgenic mice overexpressing the pim-1 oncogene in their lymphoid compartments
      are predisposed to T-cell lymphomagenesis but only to the extent that
      approximately 10% of the transgenic mice develop lymphomas within 34 weeks after
      birth. Recently, we have shown that lymphomagenesis in pim-1 transgenic mice can
      be accelerated by infecting pim-1 transgenic mice with murine leukemia viruses or
      by treating the mice with a relatively low dose of 60 mg of the carcinogen N
      ethyl-N-nitrosourea (ENU) per kg of body weight. Here we describe the incidence
      of tumors as a function of the dose of ENU. Either 200, 15, 4, 1, or 0.1 mg/kg
      ENU was injected into transgenic and control mice and the tumor incidence was
      monitored. T-cell lymphomas developed in 100 and 70% of the pim-1 transgenic mice
      treated with 200 and 15 mg/kg ENU, respectively. Approximately 20% of the Emu-pim
      1 transgenic mice developed lymphomas after treatment with either 4, 1, or 0.1
      mg/kg ENU. The nontransgenic mice developed lymphomas only after injection with
      200 mg/kg (45%). The data show that Emu-pim-1 transgenic mice are approximately
      25-fold more susceptible to ENU-induced lymphomagenesis than control mice. In
      most tumors the expression of c-myc was strongly elevated, probably as a direct
      or indirect effect of ENU. Analysis of the lymphomas for ras mutations revealed
      that approximately 10% of the lymphomas bear a ras mutation. The data indicate
      that at least some of these mutations are not the direct result of alkylation by
      ENU but rather represent spontaneous mutations that occurred later in the
      tumorigenic process.

PMID- 1988139
TI  - Peripheral blood and bone marrow immunophenotypic and functional modifications
      induced in acute leukemia patients treated with interleukin 2: evidence of in
      vivo lymphokine activated killer cell generation.
AB  - The effect of treatment with interleukin 2 (IL2) on the phenotypic and functional
      immune system of acute leukemia patients was investigated. Fifteen acute myeloid
      leukemia and acute lymphoid leukemia patients with evidence of persistent disease
      were further subdivided into two groups according to the percentage of bone
      marrow (BM) blasts: group a had 6-15% blasts and group b had 30-65%. Following
      two cycles of IL2 (Glaxo Imb, Geneva, Switzerland) given i.v. by continuous
      infusion at escalating doses, no major changes in the proportion of CD3-, CD4-,
      and CD8-positive cells were encountered in the blood or in the marrow of either
      group of patients. When these could be retested after four cycles of IL2, a
      significant increase of CD3+ and CD4+ cells was documented in the peripheral
      blood (PB), as well as a significant increase of CD3+ cells in the BM.
      Irrespective of the number of cycles administered, the proportion of CD16+ cells
      increased significantly in the blood in both groups of patients and in the marrow
      of group a patients only. The expression of CD25 was significantly enhanced in
      all samples tested. Following IL2 administration, an enhancement of the natural
      killer compartment was documented. This was consistently more evident in patients
      with more limited disease. A significant amplification of the in vitro-induced
      lymphokine-activated killer function was noted in the BM of the treated patients.
      Furthermore, we documented the presence both in the PB and in the BM of
      "spontaneous" lymphokine-activated killer cells generated in vivo following IL2
      administration. These results demonstrate that in acute leukemia of both myeloid
      and lymphoid origin, treatment with IL2 is capable of inducing profound
      immunophenotypic and functional modifications in PB and in BM lymphocytes,
      particularly in patients with more limited disease. The evidence of the in vivo
      activation of cytotoxic cells, particularly in the BM, may help to explain the
      clinical responses preliminarily observed in individual acute leukemia patients.

PMID- 1988140
TI  - An unexpected biotransformation pathway for tetrachloro-(d,l-trans)-1,2
      diaminocyclohexaneplatinum(IV) (tetraplatin) in the L1210 cell line.
AB  - Tetrachloro(d,l-trans)-1,2-diaminocyclohexaneplatinum(IV) (tetraplatin) has been
      considered a prodrug which would be converted rapidly to dichloro(d,l-trans)-1,2
      diaminocyclohexaneplatinum(II) [PtCl2(dach)] under physiological conditions.
      However, the biotransformations of tetraplatin have not been studied in detail.
      We have followed the intracellular biotransformations of tetraplatin and
      PtCl2(dach) in the L1210 cell line by a two-step high performance liquid
      chromatography separation procedure described previously (Mauldin et al., Cancer
      Res., 48: 5136-5144, 1988). At early times the intracellular biotransformation
      pathways appeared to be very different in tetraplatin- and PtCl2(dach)-treated
      cells. The tetraplatin present in the medium initially was taken up
      preferentially by the L1210 cells. However, no intracellular tetraplatin and very
      little intracellular PtCl2(dach) were found in the tetraplatin-treated cells.
      Instead, two previously unidentified biotransformation products predominated at
      early times. The same biotransformation products were present in cells incubated
      in Hank's balanced salt solution, so they most likely did not arise from
      extracellular reactions. The unidentified biotransformation products present in
      tetraplatin-treated cells at early times appeared to be at the platinum(II) level
      of oxidation. Model reactions suggested that these compounds could have been
      formed by platinum(II)-assisted platinum(IV) substitution reactions, followed by
      reduction of the platinum(IV) complex to the platinum(II) level. Thus, there
      appear to exist unique features of tetraplatin metabolism which are observed only
      when tetraplatin is taken up directly by the cell without prior reduction. These
      reaction products did not react with DNA and presumably represent an inactivation
      pathway.

PMID- 1988141
TI  - Induction of heme oxygenase: a general response to oxidant stress in cultured
      mammalian cells.
AB  - Accumulation of heme oxygenase mRNA is strongly stimulated by treatment of
      cultured human skin fibroblasts with ultraviolet radiation, hydrogen peroxide, or
      the sulfhydryl reagent sodium arsenite (S. M. Keyse and R. M. Tyrrell. Proc.
      Natl. Acad. Sci. USA, 86: 99-103, 1989). Since this will result in a transient
      reduction in the prooxidant state of cells, the phenomenon may represent an
      important inducible antioxidant defense mechanism. To examine the generality of
      the response, we have measured the accumulation of the specific mRNA in a variety
      of human and mammalian cell types after inducing treatments. Induction by sodium
      arsenite is observed in all additional human cell types tested. This includes
      primary epidermal keratinocytes and lung and colon fibroblasts as well as
      established cell lines such as HeLa, TK6 lymphoblastoid, and transformed fetal
      keratinocytes. Strong induction of heme oxygenase mRNA is also observed following
      sodium arsenite treatment of cell lines of rat, hamster, mouse, monkey, and
      marsupial origin. The agents which lead to induction in cultured human skin
      fibroblasts fall into two categories: (a) those which are oxidants or can
      generate active intermediates (ultraviolet A radiation, hydrogen peroxide,
      menadione, and the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate); (b)
      agents which are known to interact with or modify cellular glutathione levels
      (buthionine sulfoximine, sodium arsenite, iodoacetamide, diamide, and cadmium
      chloride). These observations strongly support the hypothesis that induction of
      the enzyme is a general response to oxidant stress in mammalian cells and are
      consistent with the possibility that the cellular redox state plays a key role.

PMID- 1988142
TI  - Development of skin tumors in hairless mice after discontinuation of ultraviolet
      irradiation.
AB  - The development of skin tumors (mainly squamous cell carcinomas) in hairless Skh
      HR1 mice after discontinuation of a course of daily UV irradiations (wavelengths,
      280-370 nm) is compared to that when the daily irradiations are continued. Under
      conditions of continued daily exposures 50% of 22 animals contracted tumors with
      diameters of at least 4 mm in 135 days. With exposures stopped after 35 or 19
      days (2 groups with 24 and 23 mice) this time interval increased to 280 and 645
      days, respectively; the rate at which multiple tumors developed on the mice was
      correspondingly lower. A mathematical model, derived from a larger experiment
      (223 mice) with different levels of chronic UV exposure, successfully predicts
      the tumor development after discontinuation of UV exposure. This model is similar
      to those used in risk assessments for skin cancers in human populations, e.g., in
      relation to stratospheric ozone depletion, sunbeds, etc. The model separates UV
      driven processes from purely time-dependent processes. These stochastic
      processes, described by Weibull statistics, form stages in the tumorigenesis.
      This interpretation of the data indicates that a late, UV-independent stage
      occurs between the smallest observable tumors and larger ones with diameters of
      over 4 mm. This could be a simple growth stage, but histopathology suggests that
      it may also entail a transition from actinic keratosis to squamous cell
      carcinoma.

PMID- 1988143
TI  - Development and characterization of a melphalan-resistant human multiple myeloma
      cell line.
AB  - We present data describing a human myeloma cell line (8226/LR-5) selected for
      resistance to melphalan which exhibits a 7-fold level of resistance to melphalan
      and is partially cross-resistant to other bifunctional alkylators and X
      irradiation. Melphalan resistance is relatively unstable with a decrease in
      resistance observed within 17 weeks in the absence of drug. The resistance
      observed in this cell line is not mediated by reduced intracellular melphalan
      accumulation. DNA interstrand cross-linking at equivalent intracellular drug
      accumulation is significantly reduced in the resistant subline. Whether this
      reduction is the result of a decrease in the formation of this lesion or to an
      increased rate of removal of the lesion remains to be determined. Growth
      characteristics and cell cycle kinetics, including S phase, were similar between
      sensitive and resistant cell lines. Intracellular nonprotein thiols were found to
      be significantly elevated in the resistant 8226/LR-5 cells; as cells revert or
      lose resistance, intracellular nonprotein sulfhydryl levels decline. Prior
      treatment of the cells with buthionine sulfoximine significantly reduced
      nonprotein sulfhydryl levels and enhanced melphalan cytotoxicity in both the
      sensitive and resistant cell lines. Thiols appear to play a role in mediating
      melphalan resistance.

PMID- 1988145
TI  - Retraction--autoimmune T cells: immune recognition of normal and variant peptide
      epitopes and peptide-based therapy.

PMID- 1988146
TI  - Molecular themes in oncogenesis.

PMID- 1988144
TI  - Defensins: endogenous antibiotic peptides of animal cells.

PMID- 1988147
TI  - Cooperation between oncogenes.

PMID- 1988148
TI  - Growth factors in development, transformation, and tumorigenesis.
AB  - Mammalian tissue development and regeneration take place within a milieu of
      regulatory growth factors. These affect many parameters of cell development, such
      that survival, proliferation, differentiation, and certain aspects of cell
      behavior are all influenced by a balance between stimulatory and inhibitory
      signals. The precise effect of any given factor is determined by the responding
      cell type, the concentration of factor, and the presence of other stimuli, such
      that some growth factors may fulfill a variety of functions under different
      circumstances. Classically, growth factor stimuli are transmitted into the cell
      via activation of specific, transmembrane receptors that modify key regulatory
      proteins in the cytoplasm. These in turn affect the decisions controlling
      proliferation and differentiation, including changes in gene expression and
      reactivity to other factors. There are indications that some factors may function
      both extra- and intracellularly and that this characteristic is correlated with
      potential oncogenicity. The relatively low transforming ability of extracellular
      factors alone is probably attributable to the limitations imposed by down
      regulation of their cell surface receptors. Aberrant production of secreted
      growth factors can, however, play decisive roles in tumorigenesis by increasing
      the proliferation rate and degree of cellular autonomy and extending the area
      available for tumor expansion.

PMID- 1988149
TI  - Oncogenic conversion by regulatory changes in transcription factors.

PMID- 1988150
TI  - Tumor suppressor genes.

PMID- 1988151
TI  - Leukemia and the disruption of normal hematopoiesis.

PMID- 1988152
TI  - HIV-1: the infective process in vivo.

PMID- 1988153
TI  - Expression of positional information during cell differentiation of Caulobacter.
AB  - The asymmetric targeting of proteins to the Caulobacter predivisional cell poles
      yields dissimilar progeny. We show that the products of transcriptional reporter
      gene fusions to a flagellin gene and to the flagellar hook operon are segregated
      to the progeny swarmer cell. This segregation does not depend on sequences within
      the mRNA, but on the upstream regulatory region. The subset of developmentally
      regulated flagellar genes that exhibit mRNA segregation has the same upstream cis
      acting elements: an activator-binding site known as the ftr sequence and an IHF
      binding site. We propose that these genes are preferentially transcribed from the
      chromosome in the incipient swarmer cell pole of the predivisional cell.

PMID- 1988154
TI  - Induction of specific storage organelles by von Willebrand factor propolypeptide.
AB  - Endothelial cells store the multimeric adhesive glycoprotein von Willebrand
      factor (vWf), which promotes the formation of a platelet plug at the site of
      vessel injury. To investigate the packaging of vWf into the granules called
      Weibel-Palade bodies, we expressed pro-vWf cDNA and cDNA lacking the prosequence
      in a variety of cell lines. Storage granules formed only in cells that contain a
      regulated pathway of secretion. Furthermore, packaging required the prosequence.
      Pro-vWf, lacking the C-terminal region involved in interchain disulfide bonding,
      formed granules. We conclude that the signal for storage is universal in that an
      adhesive glycoprotein can be stored by a hormone-secreting cell; the storage of
      vWf is independent of its covalent multimeric structure; the unusual rod shape of
      Weibel-Palade bodies is due to vWf; and the vWf propolypeptide is necessary for
      the formation of vWf storage granules.

PMID- 1988155
TI  - A novel protein kinase homolog essential for protein sorting to the yeast
      lysosome-like vacuole.
AB  - The VPS15 gene encodes a novel protein kinase homolog that is essential for the
      efficient delivery of soluble hydrolases to the yeast vacuole. Point mutations
      altering highly conserved residues within the Vps15p kinase domain result in the
      secretion of multiple vacuolar proteases. In addition, the in vivo
      phosphorylation of Vps15p is defective in these kinase domain mutants, suggesting
      that Vps15p may regulate specific protein phosphorylation reactions required for
      protein sorting to the yeast vacuole. Subcellular fractionation studies further
      demonstrate that the 1455 amino acid Vps15p is peripherally associated with the
      cytoplasmic face of a late Golgi or vesicle compartment. This association may be
      mediated by myristate as Vps15p contains a consensus signal for N-terminal
      myristoylation. We propose that protein phosphorylation may act as a molecular
      "switch" within intracellular protein sorting pathways by actively diverting
      proteins from a default transit pathway (e.g., secretion) to an alternative
      pathway (e.g., to the vacuole).

PMID- 1988156
TI  - The dorsal morphogen is a sequence-specific DNA-binding protein that interacts
      with a long-range repression element in Drosophila.
AB  - A gradient of the maternal morphogen dorsal (dl) establishes dorsal-ventral (D-V)
      polarity in the early Drosophila embryo. The dl concentration gradient is
      initiated by regulated nuclear transport, and only protein that enters nuclei is
      active in the D-V patterning process. Here we show that dl is a DNA-binding
      protein that specifically interacts with distal sequences of the zerknullt (zen)
      promoter, one of the genetic targets of the morphogen. These zen sequences have
      the properties of a silencer element and can act over long distances to repress
      the expression of a heterologous promoter. The dl protein recognizes a sequence
      motif similar to that of the mammalian transcriptional activator NF-kappa B,
      which was shown to contain extensive homology with dl and the oncoprotein rel. We
      present evidence that the DNA-binding activity of the dl protein is mediated by
      the region of homology (the rel domain) conserved in the rel and NF-kappa B
      proteins.

PMID- 1988157
TI  - In vivo administration of low-dose human interleukin-2 induces lymphokine
      activated killer cells for enhanced cytolysis in vitro.
AB  - We have examined the effect of the intradermal administration of IL-2 on the
      generation of natural killer (NK) cell and lymphokine-activated killer (LAK) cell
      activity. Peripheral blood mononuclear cells (PBMC) obtained from borderline
      lepromatous (BL) and lepromatous leprosy (LL) patients and normal volunteers
      prior to and after IL-2 injection were stimulated in vitro with IL-2 and their
      cytolytic activities compared against 51Cr labeled target K562 cells, Daudi
      cells, and monocytes. Before IL-2 administration, PBMC obtained from BL/LL
      patients and normal volunteers possessed similar levels of NK cell activity
      indicating that the NK cell activity of the BL/LL patients was intact. LAK cell
      activity was induced with IL-2 in vitro in both BL/LL patients and in normal
      volunteers. The level of LAK cell activity in BL/LL patients was, however,
      suboptimal. A single intradermal dose of 25 micrograms IL-2 had no effect on the
      phenotype of circulating mononuclear cells in either patients or normal
      volunteers. However, 6-12 days after IL-2 injection and subsequent restimulation
      of the PBMC with IL-2 in vitro, cytolytic activity of LAK cells obtained from the
      BL/LL patients was enhanced while cells from normal volunteers expressed the same
      high levels of activity as observed before IL-2 injection.

PMID- 1988158
TI  - Effect of micellar and bilayer gangliosides on proliferation of interleukin-2
      dependent lymphocytes.
AB  - Micellar gangliosides are potent inhibitors of the proliferation of the murine
      interleukin-2-dependent cell lines HT-2 and CTLL-2 in vitro. The glycolipids
      abolished both DNA and protein synthesis, and depressed cellular expansion,
      without affecting viability. These effects were reversible for at least 12 hr
      following ganglioside treatment. Highly sialylated gangliosides were more
      inhibitory, while structurally related molecules, including ganglioside
      oligosaccharides, simple and complex neutral glycosphingolipids, sulfatides,
      sphingomyelin, ceramides, and sphingosine had only small suppressive effects.
      Gangliosides were most effective as inhibitors when added during the first 4 hr
      of culture with the growth factor. Inhibition of DNA synthesis by gangliosides
      could be partially reversed by high concentrations of exogenous interleukin-2.
      Gangliosides incorporated into lipid bilayers, both multilamellar liposomes and
      unilamellar vesicles, were also effective inhibitors of interleukin-2-induced
      proliferation. Competition studies showed that both ganglioside micelles and
      lipid vesicles containing gangliosides prevented binding of 125I-interleukin-2 to
      high-affinity receptors on the lymphocyte surface. We have recently shown that
      gangliosides, in both micelles and lipid bilayer vesicles, are able to bind
      interleukin-2 (J. W. K. Chu and F. J. Sharom, Biochim, Biophys. Acta 1028, 205,
      1990). Taken together, these results strongly suggest that inhibition of
      lymphocyte proliferation by gangliosides in micelles and vesicles arises as a
      direct result of competition between the glycolipids and high-affinity receptors
      for available interleukin-2.

PMID- 1988159
TI  - A novel cofactor produced by a thymic epithelial cell line: promotion of
      proliferation of immature thymic lymphocytes by the presence of interleukin-1 and
      various mitogens.
AB  - Three thymic epithelial cell lines (TEC1C5, TEC1-4, and TEC2-3) were established
      from the thymus of newborn C57BL/6 mice. TEC1C5 was revealed to be an interleukin
      (IL)-1 producing cell line. TEC1-4 produced a cofactor to promote proliferation
      of double negative (CD4-8-) thymic lymphocytes by the presence of IL-1.
      Production of the same cofactor was also seen in TEC2-3, but only when it was
      cultured by the presence of indomethacin. The chemical analysis of the TEC1-4
      culture supernatant by ion-exchange column and sodium dodecyl sulfate
      polyacrylamide gel electrophoresis indicated that the factor was approximately 35
      kDa in molecular weight. The present study revealed that a factor produced by
      TEC1-4 acted as a cofactor to promote the proliferation of immature T cells
      stimulated by IL-1 and various mitogens and was considered to be a new one in
      terms of molecular weight.

PMID- 1988160
TI  - The role of the transferrin receptor for the activation of human lymphocytes.
AB  - The proliferative response of peripheral blood mononuclear cells (PBMC) in
      synthetic serum-free media depends on the presence of sufficient amounts of
      transferrin (Tf). In the present communication we show that the reduction of Tf
      concentration in culture media results in a decreased proliferation, whereas
      lymphokine production and the expression of activation markers (IL-2 receptor;
      transferrin receptor, (TfR); HLA class II) remain unchanged. To examine whether
      this effect is due to iron depletion we added iron chelates (ferric citrate,
      FeCi; ferric nitrilotriacetic acid, FeNTA) which can be internalized by cells
      without the requirement for Tf. The iron chelates could fully restore the
      proliferative response even in complete absence of Tf, suggesting that the
      observed inhibitory effect was indeed caused by iron depletion. Addition of a
      monoclonal TfR antibody, J 64, also caused a marked inhibition of proliferation
      of PBMC in regular serum-containing medium as well as in Tf-free synthetic
      medium; this effect could not be overcome by any of the tested iron chelates.
      Therefore, growth inhibition caused by J 64 cannot simply be attributed to iron
      starvation. These data suggest that J 64 may interfere with processes others than
      iron uptake and that the TfR might confer a necessary promoting signal for
      lymphocyte proliferation.

PMID- 1988161
TI  - Recombinant human interleukin 6 (rhIL-6) promotes the terminal differentiation of
      in vivo-activated human B cells into antibody-secreting cells.
AB  - Antigen-activated peripheral blood B cells were induced by parenteral
      immunization of healthy individuals with a polyvalent pneumococcal vaccine, or
      diphtheria toxoid. Seven to nine days after immunization, high frequencies of
      antigen-specific antibody-secreting cells, representing in vivo activated
      lymphoblastoid B cells, were detectable in peripheral blood or spleen. The B cell
      enriched fractions were stimulated for 7 days with different concentrations of
      rhIL-6. Both the frequency of antibody-secreting cells and the secreted amount of
      antibody to the immunizing antigen were increased by rhIL-6 in a dose-dependent
      fashion. Stimulation with rhIL-6 did not alter the isotype distribution of
      antibody-secreting cells. A polyclonal anti-IL-6 serum completely abrogated the
      stimulatory effect of rhIL-6 on the in vitro antibody secretion. Fluorescence
      activated cell sorter analysis revealed that 25-29% of cells in the large B cell
      fraction which presumably contained the in vivo activated cells bore the IL-6
      receptor. Thus, rhIL-6 enhances the terminal differentiation of in vivo activated
      B cells into antibody-secreting plasma cells.

PMID- 1988162
TI  - Interleukin-6 production by murine B cells and B cell lines.
AB  - We have analyzed interleukin (IL)-6 gene transcription and IL-6 secretion by
      murine B cells in vitro. Mitogenic doses of lipopolysaccharide (LPS) or LPS in
      combination with F(ab')2 goat anti-mouse IgM antibodies (GAMmu), but not GAMmu
      alone, induced B cells to synthesize and release IL-6. In time course
      experiments, the accumulation of IL-6 mRNA was first detectable at 24-36 hr of
      culture and the levels were maintained through 60 hr; these kinetics correlated
      well with increases in supernatant IL-6 levels and were coincident with vigorous
      cell cycle activity. We also analyzed constitutive and LPS-induced IL-6 gene
      expression by the murine B cell lines: 70Z/3, 38C-13, WEHI-231, X16C, WEHI-279,
      and BCL1. Only the WEHI-279 and BCL1 lines produced detectable IL-6
      constitutively, and the BCL1 cells could be further induced by treatment with
      LPS. Of the remaining cell lines, only WEHI-231 and X16C could be stimulated with
      LPS to produce IL-6. To evaluate whether IL-6 could influence proliferation and
      Ig secretion by the cell lines, low cell density cultures were established in the
      presence of various doses of human rIL-6 and were assessed over time for levels
      of [3H]thymidine uptake and supernatant Ig. Under these conditions, IL-6 had no
      effect on either cell function.

PMID- 1988163
TI  - Inhibition of human antigen-specific memory B cell response in vitro by a
      diphtheria toxin-related interleukin 2 fusion protein.
AB  - Recombinant diphtheria toxin-related interleukin-2 fusion protein (DAB486IL-2) is
      specifically cytotoxic for cells bearing the high-affinity IL-2 receptor
      (p55/75). We evaluated the effects of DAB486IL-2 on the generation of tetanus
      toxoid (TT)-specific IgG antibody-forming cells in 6-day cocultures of human
      splenocytes and TT-coupled Sepharose beads. The results indicate that a
      significant portion (30-75%) of the anti-tetanus toxoid IgG response in vitro was
      susceptible to inhibition by 10(-10) M DAB486IL-2. The inhibition required both
      the IL-2 portion of the fusion protein and an active toxin moiety and was greater
      when the IL-2 toxin was added on Day 3 as compared with Day 0 of culture. The
      induction of the p55 (Tac) subunit of the IL-2R was demonstrable by two-color
      flow cytometry on a small percentage (5%) of B cells and on a higher percentage
      (10%) of non-B cells 3 days after exposure to TT-coupled Sepharose. Short-term (2
      hr) treatment of T and B cell subpopulations separated on Day 3 of culture
      followed by remixing indicated that while activated T helper cells were most
      strongly inhibited by DAB486IL-2, up to 50% of the TT-specific IgG response was
      inhibited by treatment of B cells alone with DAB486IL-2. Our results suggest that
      a strategy of eliminating human memory B cells by a combination of antigen
      activation and properly timed administration of a recombinant lymphokine-toxin
      fusion protein is feasible.

PMID- 1988164
TI  - Specific attachment of mesenteric IgA lymphoblasts to specialized endothelium of
      intestinal mucosa lamina propria capillaries.
AB  - The bulk of IgA secreted in the gut is mostly contributed by locally dwelling
      plasma cells derived from B cells originating in the gut-associated lymphoid
      tissues (GALT). These IgA cells originate in Peyer's patches and recirculate,
      returning to the gut upon maturity. The precise mechanism of homing to secretory
      mucosae is to date not fully understood. It has been demonstrated, however, that
      specialized endothelium of small vascular spaces in peripheral nodes (PN) and
      endothelia of mucosal vessels are the site of receptor recognition for B and T
      cells. In their sojourn, IgA blasts have been shown to stop momentarily in
      mesenteric nodes (MN) before proceeding to their final destination, the lamina
      propria (LP) of the gut mucosa. They then develop into IgA-secreting plasma
      cells. In the present work, we show that IgA MN lymphoblasts, when compared to PN
      lymphoblasts, attach preferentially to LP venule and capillary endothelium, The B
      cell maturation in the mesenteric lymph nodes, where IgA is the sole membrane
      bound immunoglobulin, allows attachment of most of these cells. Our work suggests
      that the site of exit of IgA cells from the circulation are these specialized
      lamina propria venules and capillaries.

PMID- 1988165
TI  - Loss of medullary dendritic cells in the thymus after cyclosporine and
      irradiation.
AB  - Cyclosporine (CsA) induces a paradoxical graft-vs-host-like disease (GVHD) in
      syngeneic rat chimeras, providing the rat has a thymus and receives mediastinal
      irradiation. Here we evaluate the effect of CsA and irradiation on the relative
      abundance of thymic dendritic cells (DC). DC were identified with an
      immunoperoxidase stain for ED1 and were quantified by computerized planimetry.
      Normal young rats have scattered DC in the cortex and numerous DC in the medulla
      with a concentration at the cortico-medullary junction. Short-term CsA induces a
      marked loss of medullary DC (798 +/- 126 cells/mm to 88 +/- 103, P less than
      0.001) and a modest loss of cortical DC (543 +/- 55 to 330 +/- 130, P less than
      0.01). While medullary DC normally recover promptly post-CsA, rats receiving
      mediastinal irradiation demonstrated minimal recovery post-CsA (P less than
      0.0003). The prolonged deficiency of medullary DC could represent an essential
      early step for loss of self-tolerance and sGVHD.

PMID- 1988166
TI  - The dynamics of conceptual change in twentieth century immunology.
AB  - I have attempted here to define three distinct eras in the 110-year history of
      the discipline of immunology. The first, extending from 1880 to about the First
      World War, centered around the new bacteriology and infectious diseases, and had
      a distinctly medical orientation. Several of the components of the original
      research program in immunology failed to maintain their original momentum or to
      fulfill their initial high promise, and went into decline. These include the
      development of new vaccines, serotherapeutic approaches, the study of cellular
      immunity, and the study of diseases that might be mediated by cytotoxic
      antibodies. Two other subprograms followed a somewhat different course; the study
      of anaphylaxis and related diseases passed primarily into the hands of clinical
      allergists, while the development and adaptation of serodiagnostic techniques
      passed into the hands of the new discipline of serology, both fields out of the
      mainstream of post-World War I immunology. As interest in the components of the
      old program was falling away, there developed a new area of interest in
      immunology. Leadership in the field devolved upon a new group of individuals with
      a predominantly chemical orientation to the study of antigens and antibodies, who
      pursued a research program and developed a theoretical base that reflected this
      orientation well. It may be interesting to examine more closely the forces
      responsible for this shift in emphasis. When interest in the old areas waned, the
      medically oriented practitioners did not switch to more immunochemical lines, but
      went in other directions. Karl Landsteiner was the only prominent "old-timer" who
      contributed significantly to the newer immunology, and it was his work that set
      the tone and attracted the new generation of immunochemists who became the
      reigning Denkkollektiv. A science does not change its precepts and approaches
      spontaneously; it is moved to the new position by those who explore fertile new
      areas. This is not to say, however, that there was no longer interesting and
      important work to be done along the old lines--it was just that such work was no
      longer "fashionable", as the reception of the work of Dienes, of Rich, of Rivers,
      and of the early Medawar illustrates. Whereas the earlier immunological program
      had interacted extensively with many different fields of biology and medicine,
      the immunochemical era was characterized by a relative introversion, as compared
      with the broad influence exerted by the earlier immunological program (92). We
      can date this second era from about the First World War until the late 1950s and
      early 1960s.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1988167
TI  - Formation of mutagenic urinary metabolites from 1-nitropyrene in germ-free and
      conventional rats: role of the gut flora.
AB  - 1-Nitropyrene (NP), an environmental pollutant, a potent mutagen and an animal
      carcinogen, undergoes reduction, acetylation, ring-hydroxylation and conjugation
      in the rat in vivo to form mutagenic metabolites which are excreted in the urine.
      In order to investigate the role of the gut flora in the generation of these
      metabolites, germ-free rats of the AGUS strain, and conventional AGUS rats
      matched for sex and age, were injected i.p. with NP labelled with 14C. The germ
      free rats excreted significantly less of the dose in urine than did the
      conventional rats. When urines were examined for mutagenicity with the Ames plate
      incorporation assay, the highest mutagenic activity was seen in the presence of
      S9 in 8-24 h urine from conventional rats. The conventional urines exceeded the
      germ-free urines by 10-fold in their content of 6-hydroxy-1-acetamidopyrene (NAAP
      6-OH), previously identified as the predominant contributor to the mutagenicity
      of the urines of rats dosed with NP and excreted mainly as its beta-glucuronide
      conjugate. Conventional Charles River CD rats treated orally with D-glucaro-1,4
      lactone, an inhibitor of beta-glucuronidase activity, excreted somewhat less NP
      derived 14C in their urines over 48 h than did matched untreated rats, and their
      8-24 h urines contained less than half as much of the mutagenic NAAP-6-OH as was
      found in the urines of the control rats. These results indicate that the gut
      flora are necessarily involved in the formation of NAAP-6-OH, and that both
      nitroreduction and the hydrolysis of glucuronides released for enterohepatic
      recirculation are essential in generating mutagenic metabolites from NP.

PMID- 1988168
TI  - The differential expression of protein kinase C genes in normal human neonatal
      melanocytes and metastatic melanomas.
AB  - Expression of protein kinase C (PKC) genes (alpha, beta, gamma and epsilon) was
      measured in cultured normal human neonatal melanocytes and metastatic melanoma
      cell strains. Three of the PKC isotypes (alpha, beta and epsilon) were
      constitutively expressed in neonatal melanocytes. Protein kinase C beta RNA
      transcripts were induced in neonatal melanocytes cultivated in medium with serum
      and 12-O-tetradecanoylphorbol-13-acetate (TPA). In contrast, PKC alpha and
      epsilon RNA transcripts were detected in melanocytes cultivated in medium without
      serum and TPA, but were repressed in melanocytes cultivated in medium with serum
      and TPA. Only PKC alpha and epsilon RNA transcripts were detected in the melanoma
      cell strains and the PKC RNA transcript expression levels varied among the five
      metastatic melanomas. In four metastatic melanoma cell strains, PKC alpha and
      epsilon RNA transcript expression levels were repressed by serum, but in one
      melanoma cell strain, PKC alpha and epsilon RNA transcript expression levels were
      induced by serum. Protein kinase C gamma RNA transcripts were not detected in
      either the melanocytes or melanoma cell strains. These data suggest an alteration
      of PKC isotype gene expression in the progression of primary melanocytes to
      metastatic melanoma. The absence of the PKC beta RNA transcripts and altered
      expression of PKC alpha and epsilon isotypes in particular may be a feature in
      the transformation of human primary melanocytes.

PMID- 1988169
TI  - Effect of dietary iron deficiency or excess on the induction of mammary
      carcinogenesis by 1-methyl-1-nitrosourea.
AB  - The hypothesis that low body iron stores are protective against cancer whereas
      high body stores promote tumor occurrence was examined in the 1-methyl-1
      nitrosourea (MNU)-induced experimental model for breast cancer. Twenty-one-day
      old female Sprague-Dawley rats were randomized into one of three experimental
      groups and fed a formulation of AIN-76A diet modified to be low in iron (2
      p.p.m.), or the same diet supplemented with an adequate (120 p.p.m.) or excess
      (1200 p.p.m.) amount of iron provided as FeSO4.7H2O. Rats were maintained on
      their respective diets throughout the experiment which was terminated 32 weeks
      post carcinogen administration. Rats were injected i.p. with either 25 mg MNU/kg
      body wt or the saline-solvent in which MNU was dissolved at 50 days of age. In
      the first 14 weeks, dietary iron deficiency resulted in a low hematocrit and a
      decrease in weight gain. The appearance of mammary tumors was markedly suppressed
      in this group compared to those given an adequate or excess level of iron. It has
      been reported in the literature that reduction in weight gain due to food
      restriction at a period immediately after carcinogen administration severely
      inhibits the subsequent development of tumors. Thus the low tumor incidence in
      the iron-deficient rats during this time frame could be attributed to the
      combined effects of low hematocrit and depressed weight gain. For the period
      between week 14 and week 32, the hematocrit in the iron-deficient animals was
      maintained at a normal level, and the body wt of these rats was comparable to
      that of the controls given an adequate level of iron. The rate of tumor
      appearance in the iron-deficient group during the second half of the experiment
      was similar to that of the iron-adequate group in the first half of the
      experiment. In other words, it appeared that once hematocrit and body wt gain
      were restored to normal in the iron-deficient animals, tumor incidence was only
      minimally affected by low dietary iron. In the second half of the experiment, the
      tumor incidence in the adequate iron group seemed to have plateaued, whereas it
      continued to rise in the excess iron group. Thus excess iron appears to be more
      prominent than iron deficiency in modification of mammary carcinogenesis,
      especially when the confounding effects of low hematocrit and reduced weight gain
      are taken into consideration in the latter case.

PMID- 1988170
TI  - Inhibition of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone carcinogenesis in
      mice by D-limonene and citrus fruit oils.
AB  - The effects of D-limonene and citrus fruit oils, i.e. orange oil and lemon oil,
      on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced neoplasia of the
      lungs and forestomach of female A/J mice were investigated. D-Limonene and the
      citrus fruit oils given p.o. 1 h prior to NNK, also administered p.o., inhibited
      pulmonary adenoma formation and the occurrence of forestomach tumors. In an
      additional experiment, D-limonene given p.o. 1 h prior to NNK administered i.p.
      again showed pronounced inhibition of pulmonary adenoma formation. This study
      provides additional data demonstrating that non-nutrient constituents of the diet
      can inhibit carcinogen-induced neoplasia when administered at a short time
      interval prior to carcinogen challenge.

PMID- 1988171
TI  - Kinds of mutations found when a shuttle vector containing adducts of 1,6
      dinitropyrene replicates in human cells.
AB  - To gain insight into the mechanisms by which carcinogens induce mutations in
      human cells, we have been comparing the frequency and spectrum of mutations
      induced when a shuttle vector, pS189, carrying covalently bound residues of
      structurally related carcinogens, replicates in human 293 cells. In the present
      study, we investigated the mutagenic effects of N-hydroxy-1-amino-6-nitropyrene,
      a partially reduced derivative of 1,6-dinitropyrene (1,6-DNP). The results were
      compared with what was found previously in the same assay with N-hydroxy-1
      aminopyrene, the partially reduced derivative of 1-nitropyrene. The shuttle
      vector plasmids were exposed to tritiated 1-nitro-6-nitrosopyrene for 1 h in the
      presence of ascorbic acid, which served as a reducing agent to generate N-hydroxy
      1-amino-6-nitropyrene. 32P-Postlabeling showed that only a single adduct was
      formed, i.e. N-(deoxyguanosin-8-yl)-1-amino-6-nitropyrene. There was a linear
      increase in the number of adducts per plasmid as a function of applied
      concentration and also in the frequency of supF mutants as a function of adducts
      per plasmid, reaching 58.8 x 10(-4) above a background of 0.8 x 10(-4). When the
      frequency of mutants induced when plasmids carrying residues of 1,6-DNP
      replicated in the human cells was compared with that induced by 1-NP residues,
      the former was 1.8 times more mutagenic than the latter. Both carcinogens induced
      mainly base substitutions, primarily G.C----T.A transversions; but 1,6-DNP
      adducts produced a significant fraction of -1 frameshifts, with most of these
      located in a unique run of five Gs in the gene. Polymerase termination reactions
      indicated that 1,6-DNP adducts were formed at every guanine, but not elsewhere in
      the gene. The 'hot spots' for adduct formation were not perfectly correlated with
      'hot spots' for mutation induction. This indicates that the ultimate biological
      effect of the chemical depends not only on the number of adducts originally
      formed, but also on such processes as cellular DNA repair, which may remove such
      adducts from the plasmids before DNA replication occurs, as well as on the
      structure of the neighboring bases at the site of the adduct.

PMID- 1988172
TI  - Metabolism of azoxymethane, methylazoxymethanol and N-nitrosodimethylamine by
      cytochrome P450IIE1.
AB  - The metabolism of azoxymethane (AOM), methylazoxymethanol (MAM) and N
      nitrosodimethylamine (NDMA) by liver microsomes from acetone-induced rats as well
      as by a reconstituted system containing purified cytochrome P450IIE1 was
      examined. The products consisted of MAM from AOM; methanol and formic acid from
      MAM; and methylamine, formaldehyde, methanol, methylphosphate and formic acid
      from NDMA. Compared to liver microsomes from untreated rats, the metabolic
      activity of acetone-induced microsomes was approximately 4 times higher for all
      three carcinogens. Using the reconstituted system, the enzyme activities (nmol
      substrate metabolized/nmol P450/min) for AOM, MAM and NDMA were 2.88 +/- 1.14,
      2.87 +/- 0.59 and 9.47 +/- 2.24 respectively. Incubations carried out in the
      presence of a monoclonal antibody to cytochrome P450IIE1 resulted in a 85-90%
      inhibition of all three reactions in this system. These results provide
      conclusive evidence that AOM, MAM and NDMA are metabolized by the same form of
      rat liver cytochrome P450. In addition, the stoichiometry of NDMA products formed
      in these reactions indicates that denitrosation, a presumed detoxication process,
      and alpha-hydroxylation, an activation reaction, are also catalyzed by the same
      cytochrome P450 isozyme.

PMID- 1988173
TI  - Enhanced expression of glutathione S-transferases in colorectal carcinoma
      compared to non-neoplastic mucosa.
AB  - Ten paired samples of primary human colorectal carcinoma and adjacent non
      neoplastic mucosa were analysed for total glutathione S-transferase (GST)
      activities as determined by 1-chloro-2,4-dinitrobenzene assays. These tissues
      were also investigated for the expression of acidic (pi), basic (alpha) and
      neutral (mu) GSTs using Western blotting procedures and immunohistochemical
      staining. For each of the paired samples examined the total GST activity was
      higher in tumour than in adjacent non-neoplastic mucosa. Western blotting, using
      an antibody against acidic GST also showed strong immunoreactivity in all the
      samples with more intense reactions in tumour compared to mucosa in nine out of
      the ten paired samples. Low levels of basic GST were also expressed in all
      samples of tumour and mucosa. Neutral GST was not detectable in two samples of
      tumour and corresponding mucosa, but low levels of expression were demonstrated
      in the remaining eight. Immunohistochemical staining for acidic GST showed a dark
      brown reaction in all tumour cells; in non-neoplastic mucosa there was positive
      immunoreactivity for epithelial cells situated deep within the crypts and a
      negative reaction for surface epithelial cells. Immunohistochemical staining for
      basic GST was negative except for one sample of tumour and two of mucosa. Neutral
      GST was expressed only in two samples of tumour and two samples of mucosa. We
      therefore conclude that there is enhanced expression of GSTs, acidic GST being
      the predominant form, in tumour compared to normal mucosa, in keeping with a role
      for GSTs in colonic carcinogenesis and acquired or innate drug resistance.

PMID- 1988174
TI  - Roles of different cytochrome P450 enzymes in bioactivation of the potent
      hepatocarcinogen 3-methoxy-4-aminoazobenzene by rat and human liver microsomes.
AB  - The potent hepatocarcinogen 3-methoxy-4-aminoazobenzene (3-MeO-AAB) has been
      reported to be bioactivated to mutagenic intermediates by rat liver microsomal
      cytochrome P450 (P450) and to be a selective inducer of rat P450IA2. In this
      study we have further investigated the roles of individual rat and human P450
      enzymes in the bioactivation of this hepatocarcinogen in a Salmonella typhimurium
      TA1535/pSK1002 system where umu response is indicative of DNA damage. 3-MeO-AAB
      was found to be bioactivated by liver microsomal enzymes from rats and humans in
      this assay system. The liver microsomal activities are increased by pretreatment
      of rats with various P450 inducers such as phenobarbital (PB), beta
      naphthoflavone (BNF), dexamethasone (DEX), acetone, ethanol, isoniazid (INH),
      diphenylhydantoin and valproic acid, and can be inhibited considerably by SKF
      525A and metyrapone. alpha-Naphthoflavone (ANF) is also an inhibitor for the
      reaction catalyzed in BNF-treated rats, but stimulated the microsomal activity in
      DEX-treated rats. Evidence has also been obtained that specific antibodies raised
      against P450IIB1, P450IA1 or IA2, P450IIE1, and P450IIIA2 inhibited the
      activation in liver microsomes from rats pretreated with PB, BNF, INH and DEX
      respectively, suggesting the possible roles of several P450 enzymes in the
      bioactivation of 3-MeO-AAB. The results obtained with reconstituted monooxygenase
      systems containing various rat P450 enzymes are highly supportive of this
      conclusion. Human liver microsomal activation of 3-MeO-AAB was also inhibited to
      various extents by antibodies raised against P450IA2, P450MP, P450IIE1 and
      P450IIIA4. In a reconstituted system containing purified forms of human P450,
      P450IA2 was the most active in catalyzing 3-MeO-AAB, followed by P450IIIA4 and
      P450MP. ANF, a known activator of P450IIIA-catalyzed reactions, caused an
      increase in activation of 3-MeO-AAB in human liver microsomal and P450IIIA4- and
      P450MP-containing reconstituted systems. From these results it is concluded that
      multiple P450 enzymes in rat and human liver microsomes are involved in the
      bioactivation of 3-MeO-AAB, regardless of its selective induction of the rat
      P450IA2 gene.

PMID- 1988175
TI  - Gastric nitrate reduction and nitrosation of trimethylurea in swine treated with
      pentagastrin or cimetidine.
AB  - Swine were treated with cimetidine in order to quantify the reduction of nitrate
      to nitrite and the gastric formation of N-nitrosotrimethylurea (NTMU) under
      conditions similar to those in the achlorhydric human stomach. Gastric-fistulated
      swine were instilled with 6.0 mmol of nitrate in 50 ml water, after which gastric
      nitrate, nitrite and pH were monitored. Trimethylurea, 250 mumol in 50 ml water,
      was instilled via the fistula 10 min following the peak gastric nitrite
      concentration. Similar experiments were conducted with pentagastrin-stimulated
      animals, in order to quantitate the effect of gastric pH and microflora on the
      presence of nitrate, nitrite and NTMU formation. The stomachs of cimetidine
      treated pigs (elevated pH) were colonized by nitrate reductase organisms to
      levels of 10(4)-10(7)/ml gastric fluid. Gastric nitrite concentration in
      cimetidine-treated animals reached a maximum of 370-2085 microM, 60 min following
      the nitrate dose. Trimethylurea was only marginally nitrosated (less than 0.1
      mumol/l gastric fluid) in cimetidine- or pentagastrin-stimulated animals. The low
      yield of NTMU at elevated pH, in the presence of substantial nitrite, suggests
      that the nitrate-reducing bacteria present in the porcine stomach did not
      catalyze trimethylurea nitrosation in vivo.

PMID- 1988176
TI  - Inhibition of azoxymethane-induced neoplasia of the large bowel by 3-hydroxy
      3,7,11-trimethyl-1,6,10-dodecatriene (nerolidol).
AB  - The inhibitory capacities of four terpenes on azoxymethane (AOM)-induced
      neoplasia of the large bowel and duodenum was studied in male F344 rats. A
      complete course of AOM administrations was given and 3 days later the rats were
      fed a semipurified diet containing 5 mg/g of the test compounds, i.e. 3-hydroxy
      3,7,11-trimethyl-1,6,10-dodecatriene (nerolidol), beta-citronellol, (+/-)
      linalool and (1R,2S,5R)-(-)-menthol or a corresponding control diet. The
      experiment was terminated 22 weeks after the last dose of AOM. Under these
      conditions, nerolidol showed an inhibitory effect on carcinogenesis of the large
      bowel. The number of rats bearing large bowel neoplasms (adenomas) was reduced
      from 82% in the controls to 33% in rats fed nerolidol and the number of
      tumors/rat from 1.5 in the controls to 0.7 in the nerolidol group. A reduction in
      adenocarcinomas of the duodenum was found but the data are not statistically
      significant. The effects of nerolidol are of interest in terms of the
      identification of a new inhibitor of carcinogenesis of the large bowel. The
      chemical structure of nerolidol suggests the possibility that the compound might
      have an impact on protein prenylation or some other aspect of the mevalonate
      pathway, but this remains to be established.

PMID- 1988177
TI  - The human glutathione S-transferases: a case-control study of the incidence of
      the GST1 0 phenotype in patients with adenocarcinoma.
AB  - The suggestion that individuals with the GST1 0 phenotype have a greater
      susceptibility to carcinogens than those with other GST1 phenotypes has been
      examined by using a starch gel zymogram approach to compare the frequency of this
      phenotype in control subjects and a group of patients with adenocarcinoma of
      stomach and colon. A significantly greater proportion of the patients with
      adenocarcinoma demonstrated the null phenotype, odds ratio analysis indicating
      that individuals with this polymorphic variant have an approximately 3-fold
      greater risk of developing these cancers.

PMID- 1988178
TI  - The mutational specificity of 2-(2-furyl)-3-(5-nitro-2-furyl)-acrylamide (AF2) in
      the lacI gene of Escherichia coli.
AB  - We have determined the mutational specificity of the 5-nitrofuran derivative
      furylfuramide (AF2) in the lacI gene of Escherichia coli. Treatment of a delta
      uvrB, pKM101 strain with 1 M AF2 yielded a mutation frequency approximately 300
      times greater than that of untreated controls. Of the 165 AF2-induced mutants
      analysed by DNA sequencing, 145 were base substitution mutations, 11 were
      frameshifts, and the remainder small deletions, tandem base substitutions and
      complex mutations. Base substitution occurred primarily (greater than 93%) at G:C
      base pairs. The proportions of the various mutations are very similar to those
      that have been reported for AP sites. We suggest that the principal mechanism for
      AF2 mutagenesis is the formation of an adduct which depurinates to yield AP sites
      that serve as a substrate for error-prone repair. Seventy-two of the mutations
      occurred at four 5'-TGC-3' sites. The majority (10/11) of the frameshift
      mutations occurred at one such hotspot and could have been templated by an
      inverted repeat less than 100 bp removed from the site of the mutation.

PMID- 1988179
TI  - Uracil-induced calculi and carcinogenesis in the urinary bladder of rats treated
      simultaneously with N-butyl-N-(4-hydroxybutyl)nitrosamine.
AB  - Urinary bladder carcinogenicity of uracil and N-butyl-N-(4
      hydroxybutyl)nitrosamine (BBN) in combination was investigated in male F344 rats.
      Two experiments were performed: in the first animals were treated with 3.0, 1.0
      and 0.3% uracil in the diet and/or 0.005% BBN in the drinking water for 36 weeks
      followed by a 4 week period without chemicals, the total observation time being
      40 weeks; in the second rats received 3.0% uracil in the diet or 0.05% BBN in the
      drinking water for 4 weeks. In the first experiment, a markedly high incidence of
      carcinomas was observed in the urinary bladder with both 3.0% uracil alone
      (11/15, 73%) and 3.0% uracil plus 0.005% BBN (18/20, 90%) treatments. The
      multiplicity, i.e. numbers of carcinomas induced per 10 cm of basement membrane,
      was significantly higher with the latter treatment (P less than 0.05), as were
      proliferative lesions in the renal pelvis. Stone formation was observed in all
      3.0% uracil treatment animals. In the second experiment, prostaglandin E2 levels
      in bladder tissue of uracil-treated animals proved to be significantly higher
      than in BBN-treated or untreated animals. Thus, the results clearly indicated
      that calculi associated with 3.0% uracil ingestion can themselves cause carcinoma
      development in the urinary bladder, while also acting as a potent co-carcinogen
      agent for BBN carcinogenesis.

PMID- 1988180
TI  - Cyclosporine promotes the induction of thymic lymphomas in C57BL/6 mice initiated
      by a single dose of gamma-radiation.
AB  - We previously demonstrated that a single dose of gamma-radiation (350 rads) was
      able to induce thymic lymphomas in C57BL mice when followed by promoting
      treatment with oral cyclosporine (CsA), a non-genotoxic immunosuppressant. We
      have now tested the efficacy of various doses of gamma-radiation as an initiator
      of CsA promotion of the induction of thymic lymphomas in male C57BL mice. The
      effects of oral CsA on the splenic natural killer (NK) cell activity of non
      irradiated and irradiated (400 rads, 1x) mice were tested by the standard 51Cr
      release assays against YAC-1 cells. The cumulative incidence of thymic lymphomas
      induced by a single dose of gamma-radiation at 100, 200, 400 and 600 rads were
      10, 25, 63 and 75% respectively, after 42 weeks of CsA promotion. The splenic NK
      cell activity in non-irradiated mice given CsA for 4 weeks was twice as high as
      that in the control mice. CsA inhibited poly I:C-induced augmentation of the
      splenic NK cell activity. In mice given a single dose (400 rads) of gamma
      radiation and CsA for 4 weeks, a similar but reduced enhancement of the splenic
      NK cell activity as seen in non-irradiated mice was observed. These results
      indicate that the efficacy of CsA promotion in the induction of thymic lymphomas
      is dependent on the initiating doses of gamma-radiation, and that CsA enhances
      host splenic NK cell activity during the early stage of tumor promotion.

PMID- 1988181
TI  - Cellular retention, cytotoxicity and morphological transformation by vanadium(IV)
      and vanadium(V) in BALB/3T3 cell lines.
AB  - Cytotoxicity, morphological transformation and cellular retention have been
      studied in BALB/3T3 Cl A 31-1-1 cells for ammonium or sodium vanadate
      [vanadium(V)] and for vanadyl sulphate [vanadium(IV)]. A morphological
      transformation focus assay showed transforming activity for vanadium(V) (P less
      than 0.005 at concentrations of 3 x 10(-6) or higher) while vanadium(IV) was not
      transforming in the cells. Cytotoxicity was higher for vanadium(V) than for
      vanadium(IV); this was particularly clear at doses from 5 x 10(-6) to 5 x 10(-5)
      M. The cellular retention of both vanadate and vanadyl compounds at 24, 48 and 72
      h incubation was similar. At concentrations lower than 10(-6) M vanadate, the
      retention was linear with the dose, while at higher exposures the vanadium taken
      up by the cells levelled off or slightly decreased. Exposure to 10(-6) M and 10(
      5) M vanadium(V) for 3 and 24 h as well as to 10(-6) M for 48 and 72 h yielded
      greater than 94% vanadium in the cytosol, but exposure to a toxic dose (10(-5) M)
      for 48 and 72 h yielded 20% vanadium associated with cellular organelles, which
      suggests that some sites in the cytosol become saturated with vanadium. The
      corresponding gel-filtration experiments indicate that a redistribution of the
      element among the cytosol components occurs with time.

PMID- 1988182
TI  - Mechanism of clastogenic and co-clastogenic activity of cremophore with benzene
      in mice.
AB  - Cremophore E1 (CR), a frequently used solubilizer and emulsifier in the
      pharmaceutical, cosmetic and animal-raising industries, is made up of ethylene
      oxide and castor oil. Since ethylene oxide has been shown to be a potent
      genotoxic agent, we have studied the clastogenic activity of CR and its co
      clastogenic activity with benzene (BZ) in mice. Male CD1 mice were divided into
      untreated, vehicle control and experimental groups. Mice in the experimental
      groups were treated orally with 0.03, 0.3 or 3% CR in water, 440 mg/kg BZ in
      olive oil, BZ plus the three different doses of CR (1 h apart) or BZ plus 3% CR
      separated by 1, 3 and 5 h intervals. Mice were killed at 30 h after the treatment
      for the single-treatment groups and after the first treatment for the combined
      treatment groups. Bone marrow cells were harvested for determination of
      micronuclei (MN) frequencies in polychromatic erythrocytes (PCE). The presence of
      known genotoxic metabolites of benzene (phenol and trans,trans muconic acid) was
      quantitated in collected urine. The effect on hepatic cytochrome P450 isoenzyme
      expression in livers of treated mice were also analyzed. We found that CR did not
      induce any significant or dose-dependent increase in MN. However, CR enhanced the
      clastogenic activity of BZ in a dose-dependent manner (from 41.6 to 47.3, 60.5
      and 67.1 MN/1000 PCE respectively; P less than 0.05). The combined treatment
      showed an inverse time-dependent change in MN frequencies when CR was
      administered at 1, 3 and 5 h after BZ (41.6 to 67.1, 43.4 and 42.0 MN/1000 PCE
      respectively). The enhancement effect of CR is apparently due to its ability to
      induce significantly the cytochrome P450I family when CR was administered 1 h
      after treatment with BZ. However, no positive synergistic effect was observed
      when the combined treatment intervals were extended to 3 and 5 h. Enhanced
      induction of these isoenzymes is correlated with increased metabolic activation
      of BZ to excrete increased amounts of trans,trans muconic acid, the putative
      active metabolite of BZ, in urine. Our integrated study demonstrates that an
      apparently innocuous agent that is consumed by the general population can enhance
      the genotoxic activity of a ubiquitous environmental carcinogen. The potential
      existence of this type of interaction in our daily lives is frequently overlooked
      and should be investigated.

PMID- 1988183
TI  - Promotion of hepatocellular foci in female rats by chenodeoxycholic acid.
AB  - Chenodeoxycholic acid (CDC), a dihydroxylated primary bile acid, was evaluated
      for promotional activity in the liver of rats using a two-stage initiation
      promotion model. CDC is a primary bile acid that can attain high concentrations
      in serum and liver during induced or naturally occurring hepatocellular
      disorders. Female Sprague-Dawley rats were injected once (i.p.) with
      diethylnitrosamine (DEN, 150 mg/kg) or sterile physiologic saline (SAL, 0.85%
      NaCl). Two weeks later, rats in each group were placed into one of two subgroups
      and fed either NIH-31 mash (Control) or NIH-31 mash containing 0.5% CDC for a 10
      week period. At the end of the feeding period, blood and liver samples were
      collected for determination of bile acid profiles and quantitation of
      hepatocellular foci respectively. Serum samples were analyzed for concentrations
      of individual bile acids using a HPLC method that utilizes a post-column
      enzymatic reaction and fluorescence detection. Liver slices from the left hepatic
      lobe were stained for foci positive for placental glutathione S-transferase. In
      serum, significant increases occurred in concentrations of all forms of CDC and
      were accompanied by mild, insignificant increases in lithocholic acid. Decreased
      serum concentrations occurred in all forms of cholic and deoxycholic acids.
      Analysis of liver sections revealed that rats treated with DEN-CDC had
      significant increases in numbers and volume of foci compared to those treated
      with DEN-Control. For rats in groups DEN-CDC and DEN-Control, the numbers of foci
      per square centimeter were 32 and 12; per cubic centimeter, 2221 and 937; and the
      per cent volume of foci, 1.487 and 0.385 respectively. In this study, CDC was a
      promoter of hepatocellular foci. Because concentrations of CDC in liver and serum
      increase in a variety of hepatobiliary disorders, the possibility that increases
      in endogenous concentrations can enhance the formation of hepatocellular foci is
      being explored.

PMID- 1988184
TI  - Selenium metabolism in isolated hepatocytes: inhibition of incorporation in
      proteins by mono(2-ethylhexyl)phthalate, a metabolite of the peroxisome
      proliferator di(2-ethylhexyl)phthalate.
AB  - Di(2-ethylhexyl)phthalate (DEHP), a rat liver carcinogen, induces peroxisomal
      proliferation and a concomitant oxidative stress, but decreases liver glutathione
      peroxidase (GSH-Px) activity. This enzyme is a selenoprotein and we have
      investigated the influence of mono(2-ethylhexyl)phthalate (MEHP), a major
      metabolite of DEHP, on selenium incorporation in hepatocellular proteins.
      [75Se]Selenious acid (6 nM) was added to primary cultures of rat hepatocytes and
      protein incorporation was assessed by SDS-PAGE and autoradiography. High
      concentrations of MEHP (1.0-3.0 mM) inhibited selenium labeling of all major
      selenoproteins in 3-24 h experiments, but also inhibited protein synthesis as
      assessed by leucine incorporation. The protein synthesis inhibition was
      reversible. Lower concentrations of MEHP (0.3-0.5 mM) did not decrease the 75Se
      labeling in 24 h experiments and did not inhibit leucine incorporation. However,
      conditions that significantly induced peroxisomal proliferation also affected the
      75Se-labeling. Thus in 72 h experiments, 0.05-0.25 mM MEHP increased the labeling
      of a 58 kd protein, decreased the labeling of a 23 kd protein (with the same mol.
      wt as GSH-Px), had no effect on a 20 kd protein and decreased the labeling of a
      15 kd protein (as compared to MEHP-free control plates). The pattern of changes
      associated with peroxisomal proliferation mimicked that seen in livers from
      selenium-deficient animals, as reported by others. These data indicate that the
      bioavailability of selenium is decreased by DEHP. This effect may relate to a
      transient inhibition of protein synthesis, but also to the DEHP-induced
      peroxisomal proliferation.

PMID- 1988185
TI  - Induction and disappearance of DNA strand breaks and/or alkali-labile sites in
      human lymphocytes exposed to N-ethyl-N-nitrosourea.
AB  - We investigated the induction and disappearance of DNA lesions that are detected
      as single-strand breaks (SSBs) with the alkaline filter elution technique, in
      human peripheral blood lymphocytes (PBLs) following exposure to N-ethyl-N
      nitrosourea (ENU). In PBLs of the 15 individuals studied, 35 +/- 16% (mean +/-
      SD) of the SSBs present at the end of a 20 min treatment disappeared within 1 h;
      up to 24 h post-treatment no further disappearance was observed. Interindividual
      differences in SSB disappearance were considerable; in two cases, almost no SSBs
      disappeared over the 1 h period. In PBLs of the same 15 individuals 85 +/- 3%
      (mean +/- SD) of the SSBs induced by 4 Gy of gamma-rays were found to disappear
      within 1 h, which indicated no interindividual differences. Multiple blood
      sampling at 1 month intervals indicated that interindividual differences in ENU
      induced SSB repair are constant and do not vary with time. The low rate of SSB
      disappearance appeared to correlate with low cell survival after ENU exposure,
      measured as a reduction in phytohemagglutinin-stimulated incorporation of [3H]
      thymidine. The cytosine analog 1-beta-D-arabinofuranosyl-cytosine completely
      inhibited SSB disappearance, indicating that the removal of the repairable ENU
      induced SSBs involves excision repair events.

PMID- 1988186
TI  - The role of O6-alkylguanine in cell killing and mutagenesis in Chinese hamster
      ovary cells.
AB  - Chinese hamster ovary cells with no detectable (less than 200 molecules/cell) O6
      methylguanine-DNA methyltransferase (EC 2.1.1.63) were transfected with human
      cell DNA and pSV2neo plasmid by electroporation. Two stable transformant clones,
      GC-1 and GC-2, containing 4 X 10(4) and 4-6 X 10(3) methyltransferase
      molecules/cell respectively were isolated by successive screening in the presence
      of G418 and 2-chloroethyl-N-nitrosourea (CNU). Only three or four copies of
      pSV2neo DNA and no repetitive human DNA sequence were detected in these isolates.
      Secondary transfection of parent cells with GC-1 DNA yielded several clones
      containing 2-10 X 10(3) methyltransferase molecules/cell. The rate of removal of
      O6-methylguanine in GC-1, GC-2 and parent cells in vivo reflected their
      methyltransferase levels, while the N-methylpurines were removed at similar rates
      in all three cell lines. The differential sensitivity of these cells to several
      alkylating agents, namely CNU, N-methyl-N-nitrosourea, N-methyl-N'-nitro-N
      nitrosoguanidine and methyl-methane sulfonate (MMS), known to yield different
      proportions of O6-alkylguanine among the alkyl adducts in DNA, varied widely. The
      largest and smallest differences in toxic response were observed with CNU and MMS
      respectively. These cell lines showed no difference in sensitivity to the DNA
      cross-linking agent psoralen. These data strongly suggest that alkylating agents
      produce two classes of lethal lesions, one of which is O6-alkylguanine. Induction
      of mutations at the hypoxanthine-phosphoribosyltransferase locus in these cells
      lines suggests that, regardless of its relative yield, O6-methylguanine is the
      major mutagenic lesion for all alkylating agents.

PMID- 1988187
TI  - Enhanced hydroperoxide production by peripheral blood leukocytes following
      exposure of murine epidermis to 12-O-tetradecanoylphorbol-13-acetate.
AB  - Previous studies have shown that the phorbol ester tumor promoter 12-O
      tetradecanoylphorbol-13-acetate (TPA) stimulates phagocytic leukocytes to produce
      reactive oxygen intermediates in vitro. The present studies focused on the
      production of reactive oxygen intermediates by peripheral blood leukocyte cell
      populations following in vivo exposure of murine epidermis to TPA. TPA induced a
      dose-dependent (0.2-20 micrograms) increase in polymorphonuclear cells (PMN) that
      appeared to be recruited from the marginal pools, while simultaneously decreasing
      the number of peripheral blood mononuclear cells. These alterations were detected
      as early as 2 h following topical application of TPA and persisted over a 21 day
      time period, using a twice-weekly TPA treatment schedule. The oxidation of 2',7'
      dichlorofluorescin (DCFH) was used to examine the hydroperoxide production in
      peripheral blood PMN isolated from SENCAR mice treated with TPA. TPA stimulated a
      2-fold increase in PMN-associated DCFH oxidation (645.4 +/- 118 fmol DCF) 4 h
      after topical application of 10 micrograms TPA when compared to PMN isolated from
      acetone-treated mice (339.0 +/- 35.8 fmol DCF). These observations suggest that
      topical application of TPA recruits PMN that are activated prior to their
      infiltration into the epidermis. Given the ability of these cells to migrate to
      local sites, they may serve as a primed cell population that significantly
      contributes to cutaneous alterations observed during acute and chronic
      inflammation following TPA exposure.

PMID- 1988188
TI  - Establishment of a reference interval for beta 2-microglobulin in cerebrospinal
      fluid with use of two commercial assays.
AB  - Increased concentrations of beta 2-microglobulin in cerebrospinal fluid have been
      used to detect central nervous system involvement with metastatic cancer and with
      neurological complications of AIDS. However, no adequate reference interval study
      has been reported for beta 2-microglobulin in cerebrospinal fluid. We established
      a reference interval with both the Abbott IMx microparticle enzyme-linked
      immunoassay (EIA) (0.6-2.0 mg/L) and the Pharmacia beta 2-micro EIA 96 method
      (0.8-2.2 mg/L) for beta 2-microglobulin in cerebrospinal fluid. The two methods
      correlate well, with the latter method giving slightly higher values. beta 2
      Microglobulin increases with age in adults by about 0.1 mg/L every 7.5 years,
      with no significant difference between genders.

PMID- 1988189
TI  - Sweat sodium or chloride?

PMID- 1988190
TI  - An ultrafiltrate of saliva collected in situ as a biological sample for
      diagnostic evaluation.

PMID- 1988191
TI  - Free triiodothyronine concentrations as measured by two one-step
      radioimmunoassays in nonthyroidal illness.

PMID- 1988192
TI  - Total lactate dehydrogenase and its isoenzymes in serum of patients with
      infectious mononucleosis.

PMID- 1988193
TI  - Use of affinity chromatography in developing acridinium ester-labeled antibodies
      for an immunometric assay of parathyrin.

PMID- 1988194
TI  - A new look at the role of urinalysis in the history of diagnostic medicine.
AB  - Before this century, urine was the predominant body fluid used by the physician
      for diagnosis and prognosis. Uroscopy, or urinalysis by the senses, has usually
      been treated disparagingly in historical accounts of diagnostic medicine.
      Although uroscopy was at times used fraudulently, the thoughtful use of
      urinalysis was probably an important part of diagnosis for the physician, even
      before the chemical analysis of urine.

PMID- 1988195
TI  - Total plasma homocysteine determination in subjects with premature cerebral
      vascular disease.

PMID- 1988197
TI  - Earlier work overlooked: going Dutch.

PMID- 1988196
TI  - Do enzymatic analyses of serum triglycerides really need blanking for free
      glycerol?

PMID- 1988198
TI  - Apparent stability of aminotransferases: influence of the analytical method.

PMID- 1988199
TI  - Neonatal hypothyroid screening with thyrotropin kit and an overweekend incubation
      protocol.

PMID- 1988201
TI  - Best buffer for routine alkaline phosphatase assays.

PMID- 1988200
TI  - Calibrating assays of direct bilirubin.

PMID- 1988202
TI  - Digoxin-like immunoreactivity in saliva and plasma of pregnant women.

PMID- 1988203
TI  - Capillary electrophoresis--a new clinical tool.
AB  - The potential clinical diagnostic utility of capillary electrophoresis in an open
      tubular column is established. Separation patterns for serum proteins by
      conventional agarose gel electrophoresis can be faithfully reproduced by a
      capillary electrophoresis procedure that provides the complete run data in 8 min.
      Hemoglobin variants can be separated within 10 min. The capillary electrophoresis
      separations are performed reliably and reproducibly in an untreated 75 micron
      (i.d.) x 25 cm fused-silica column. Diluted serum or hemoglobin samples can be
      loaded on an automated instrument with on-line injection, detection, and
      quantification, providing a truly "walkaway" electrophoresis system.

PMID- 1988204
TI  - Microparticle-enhanced nephelometric immunoassay (Nephelia) for immunoglobulins
      G, A, and M.
AB  - Covalent binding of gamma chains of IgG, whole IgA, and mu chains of IgM on
      polyfunctional hydrophilic microspheres (MS) yields MS-Ig conjugates, usable as
      reagents in new microparticle-enhanced nephelometric immunoassays (Nephelia). The
      principle of the assays is inhibition by free analyte (IgG, IgA, and IgM) of
      agglutination of the MS-Ig conjugate with specific antiserum, the light scattered
      by the aggregates being measured with a nephelometer. The immunoglobulin assays
      developed are easy to perform (single-step assays, no washing or phase
      separation) and sensitive (high dilution of biological samples to exclude
      interferences and pretreatment). Analytical recovery results (95.4-101.2%) and
      correlations with generally used commercial assays (r = 0.86-0.98) indicate that
      the assays are accurate for large concentration ranges of immunoglobulins.
      Precision study gives CVs = 2.8-9.6%. Nephelia appears to be useful for
      quantifying a large variety of biological molecules.

PMID- 1988205
TI  - Multi-factor designs. IV. How multi-factor designs improve the estimate of total
      error by accounting for protocol-specific biases.
AB  - Total error is often calculated as a combination of random error and fixed bias.
      However, the specific protocols used to estimate random error and fixed bias are
      themselves variable factors that can affect the estimate of total error. We refer
      to biases such as assay drift, sample-to-sample carryover, and reagent carryover
      as examples of fixed biases that are protocol-specific and distinguish them from
      other fixed biases. Failing to account for protocol-specific biases that are
      present will lead to incorrect estimates of total error when routine use of the
      assay involves a protocol different from that used to estimate total error. Multi
      factor protocols are recommended to determine protocol-specific biases, which, if
      present, should be included in the estimate of total error.

PMID- 1988206
TI  - Logistic-regression model for assessing portal hypertension by measuring
      hyaluronic acid (hyaluronan) and laminin in serum.
AB  - We earlier observed a positive correlation between portal venous pressure (PVP)
      and the concentration of laminin in serum. Here we investigated whether the
      diagnostic efficacy could be improved by considering additional analytes and
      application of multivariate statistical analysis. In 102 patients with fibrotic
      liver disease of various etiologies we measured PVP as the gradient of the wedged
      and free hepatic venous pressures and determined the concentrations of hyaluronic
      acid and laminin in serum. Regression coefficients established by logistic
      regression in this group were subsequently used to predict portal hypertension
      (PVP greater than mmHg) in an independent group of 45 patients. By comparison
      with the known PVP, we obtained a sensitivity of 0.83 (confidence interval: 0.63
      0.93) and a specificity of 0.82 (0.61-0.93) for diagnosis of portal hypertension
      by means of the concentrations of hyaluronic acid and laminin in serum.
      Application of the model is suggested as a tool for pre-screening and monitoring
      patients to be subjected to assessment of portal hypertension.

PMID- 1988207
TI  - Urinary neopterin in patients with systemic lupus erythematosus.
AB  - Concentrations of neopterin were measured in urine specimens from 35 patients
      with active and eight with inactive systemic lupus erythematosus (SLE). Compared
      with those of apparently healthy controls, neopterin concentrations were higher
      in patients with active disease (P less than 0.001) and with inactive disease (P
      less than 0.01), those in patients with active disease being significantly higher
      than those in patients with inactive disease (P less than 0.001). The correlation
      between the neopterin concentration and evidence of disease activity was good.
      All of the patients with clinically active SLE had increased neopterin, but for
      only 37.5% (three of eight) did the neopterin concentration exceed the upper
      normal limit during clinical remission. The increase in neopterin concentration
      did not correlate with clinical courses or severity of renal function. Moreover,
      serial determinations of neopterin in active SLE patients showed a rapid decrease
      of initially high concentration, paralleling a decline of clinical activity after
      initiation of medical therapy. Thus, urinary neopterin may be a useful marker for
      monitoring disease activity in SLE patients.

PMID- 1988208
TI  - Monitoring treatment of alcoholic liver disease: evaluation of various severity
      indices.
AB  - Monitoring the effectiveness of treatment sfor alcoholic liver disease involves
      the use of variables that have prognostic significance and are unaffected by the
      treatment in unspecific ways. Here we review the value of histological and
      functional variables for this purpose. We conclude that histological variables,
      although important in defining the characteristics of the sample, have several
      practical problems. The functional variables are most effective when used in
      combinations, e.g., in global indices such as the Combined Clinical and
      Laboratory Index, the Child-Turcotte-Pugh Index, or the Cox model. In situations
      involving mortality and dropouts, functional indices cannot be used to measure
      changes in severity; in such cases, mortality might be the only measure for
      assessing the effectiveness of a treatment. In clinical trials, it is essential
      to determine the risk of a Type II error, to monitor compliance and drinking, and
      to trace appropriately all the patients who were not compliant or who dropped out
      of the trial.

PMID- 1988209
TI  - Human anti-murine antibody interference in measurement of carcinoembryonic
      antigen assessed with a double-antibody enzyme immunoassay.
AB  - Fifty-eight plasma specimens from 30 patients who had undergone presurgical
      radioimmunoscintigraphy with 111In-labeled anti-carcinoembryonic antigen (CEA)
      murine monoclonal antibody (Mab) and who had no clinical evidence of disease
      after surgical resection showed increased concentrations of CEA (greater than or
      equal to 5 micrograms/L) in plasma when studied with the previously available
      commercial CEA enzyme immunoassay (EIA) from Roche. The possible role of anti
      murine antibody (HAMA) interference was addressed by adding mouse IgG (mIgG) to
      the plasma (2 g/L) before assay. Fifteen specimens (26%) showed no change in CEA
      (reflecting a true increase as shown by the original results), 22 (38%) showed a
      decrease in CEA of greater than 15% but remained positive (reflecting an
      artefactual increase), and 21 (36%) became CEA-negative (less than or equal to 5
      micrograms/L; reflecting a false increase). Subsequently, we assayed the same
      samples with a modified version of this CEA EIA kit and 47 specimens remained CEA
      positive (greater than 5 micrograms/L): 25 (53%) were truly increased, 12 (26%)
      remained artefactually increased, and 10 (21%) continued to show a false
      increase. The degree of interference in the original EIA kit correlated with the
      plasma concentration of HAMA (P less than 0.005). All artefactually and falsely
      increased CEA values observed in both kits were corrected by addition of
      polyclonal mIgG or of a mixture of IgG1, IgG2a, and IgG2b Mabs before assay. This
      correction is important in the follow-up of patients who receive murine Mabs for
      treatment or diagnosis.

PMID- 1988210
TI  - Novel application of streptavidin-hapten derivatives as protein-tracer conjugate
      in competitive-type immunoassays involving biotinylated detection probes.
AB  - To investigate the use of streptavidin-hapten derivatives as potential protein
      tracer conjugates for competitive-type immunoassays, we labeled streptavidin with
      cortisol and compared biotin-binding activity of the conjugates with that of
      unlabeled streptavidin. In this model system, streptavidin labeled with one to
      approximately 17 cortisol molecules retained its capability to cross-link a
      biotinylated protein on microtiter wells to a biotin-based general detection
      reagent developed for time-resolved fluorometry. Compared with unlabeled
      streptavidin, there was no reduction in the binding activity of the conjugate
      carrying as many as 2.6 cortisol molecules per molecule of streptavidin.
      Conjugation ratios greater than 4.4 showed a slight decrease in binding activity,
      presumably because of the aggregate formation evident at these labeling ratios.
      As expected, the conjugates were also capable of linking a solid-phase-bound anti
      cortisol monoclonal antibody to the biotinylated detection reagent. The
      fluorescence signal generated increased almost linearly with increasing
      conjugation ratios from about three to nine cortisol molecules per molecule of
      streptavidin. At greater ratios, the assay response plateaued. The calibration
      curves obtained were typical for competitive-type immunoassays when the
      conjugates were incorporated in a cortisol assay based on a second-antibody
      immobilization approach.

PMID- 1988211
TI  - Protein A-sepharose used to measure free insulin in plasma.
AB  - Diabetic patients receiving insulin therapy generally develop anti-insulin
      antibodies that must be eliminated, usually by extraction with polyethylene
      glycol (PEG), before determining the concentration of free (active) insulin in
      plasma. We describe a new method for removing such antibodies, with the use of
      Protein A coupled to Sepharose microspheres. The results correlate well with
      those by the PEG method, although values are systematically higher or lower for
      given samples, according to the initial titer of the antibody measured in terms
      of binding capacity. Further studies are required to clarify this observation.

PMID- 1988212
TI  - Immunoradiometric assay of myosin heavy chain fragments in plasma for
      investigation of myocardial infarction.
AB  - Estimation of the extent and location of infarct is important for the prognosis
      and hence therapeutic strategy in patients with acute myocardial infarction
      (AMI). Because cardiac myosin is the major structural protein of the myocardium,
      and may thus reflect the extent of injured tissue, we established a new sensitive
      immunoradiometric assay, using a pair of monoclonal antibodies (Mabs) that
      specifically bind the myosin heavy chain fragments liberated from the myocyte
      into plasma after a heart attack. A first Mab is linked to a magnetic solid
      phase. A second Mab, radiolabeled with 125I, is used to detect myosin trapped on
      the solid phase by the first Mab during a 3-h incubation. This assay can detect
      10 micro-units of myosin per liter and is highly reproducible.

PMID- 1988213
TI  - Investigation of urinary crystals by Fourier transform infrared microscopy.
AB  - Although crystalluria is generally considered a normal finding, sometimes it
      gives evidence of renal disturbance. Thus, detection and identification of
      urinary crystals may provide useful data for understanding the etiology of
      mechanism of the disorder. Light microscopy may be not sufficient to accurately
      identify the crystals. We investigated the ability of Fourier transform infrared
      microscopy (FTIRM) to identify isolated crystals of clinical interest. Twenty
      five urine samples presenting crystalluria were tested because of their unusual
      aspect. We successfully identified 16 compounds and showed that crystals with the
      same apparent morphology can be composed of different substances. Moreover, an
      unexpected structure may be an insoluble phase of a drug metabolite. We conclude
      that FTIRM is a good technique for investigating urinary crystals of clinical
      interest.

PMID- 1988214
TI  - Isoelectric focusing electrophoresis of protein-ligand conjugates: effect of the
      degree of substitution.
AB  - The degree of substitution of protein-ligand conjugates can be determined from
      the change of the isoelectric point (pI) of the protein when ligand molecules are
      attached to its surface. Specifically, the pI values of conjugates with known
      degrees of substitution are obtained by isoelectric focusing electrophoresis and
      are used to generate a calibration curve that relates these two variables. The
      shape of the curve is sigmoidal and can be predicted by a theoretical model that
      takes into account the degree of substitution and the amino acid composition of
      the protein. By using such a calibration curve, one may estimate the degree of
      substitution of a given protein-ligand conjugate from its pI value. The
      applicability of the method is demonstrated with conjugates of pyridoxal 5
      phosphate and avidin.

PMID- 1988215
TI  - Ion-chromatographic determination of L-tartrate in urine samples.
AB  - We propose using ion chromatography to determine tartrate concentration in urine.
      A 100-microL sample of urine is diluted and injected into the chromatograph.
      Tartrate is eluted within 11.5 min as a distinct and well-resolved peak. The
      sensitivity of the standard procedure (signal-to-noise ratio, 3/1) is 30 mumol/L.
      The intra-run and interrun coefficients of variation are 2.5% and 4.1%,
      respectively. Mean analytical recovery of known amounts of added tartrate ranges
      between 94.2% and 104.0%. We investigated the specificity of the procedure by
      analyzing urine containing added dicarboxylic acids structurally related to
      tartrate. The reliability of the procedure makes it suitable for investigating
      tartrate metabolism, e.g., the potential role of tartrate as an inhibitor of
      crystallization in calcium nephrolithiasis.

PMID- 1988216
TI  - Digoxin-like immunoreactivity in serum from neonates and infants reduced by
      centrifugal ultrafiltration and fluorescence polarization immunoassay.
AB  - We evaluated the TDx Digoxin II (Abbott) modified procedure for interference from
      digoxin-like immunoreactive factors (DLIF) in pediatric patients. The
      effectiveness of centrifugal ultrafiltration as a means of removing DLIF
      interference from the serum of such patients was assessed. We used sera from 40
      patients who had not received digoxin, whom we divided into two age groups: 30
      neonates (less than 34 days postpartum) and 10 infants (younger than six months).
      Digoxin-like immunoreactivity was detected in 34 of 41 (83%) neonatal specimens
      (range 0.2-1.0 micrograms/L) and 16 of 25 (60%) infants' specimens (range 0.2-1.3
      micrograms/L). Centrifugal ultrafiltration of serum specimens from these patients
      reduced but did not eliminate the DLIF interference in some specimens. A
      comparison of concentrations of DLIF in serum with various other patients'
      characteristics demonstrated a strong correlation (r = 0.915; P = 0.0001) between
      DLIF and serum bilirubin in the infants. Apparent digoxin concentrations from 19
      serum and serum ultrafiltrate samples collected from 13 patients (four neonates
      and nine infants) who were treated with digoxin showed a good correlation (r =
      0.97); however, the serum samples showed a positive bias of 0.39 microgram/L. We
      conclude that the TDx Digoxin II modified procedure is still subject to
      considerable DLIF interference in these two pediatric populations. This
      interference can be reduced in some serum specimens, but cannot be eliminated
      completely as others reported.

PMID- 1988217
TI  - Displacement of phenytoin from serum protein carriers by antibiotics: studies
      with ceftriaxone, nafcillin, and sulfamethoxazole.
AB  - Increased concentrations of free phenytoin in serum, attributable to the
      displacement of this anticonvulsant by other drugs, e.g., valproic acid and
      salicylic acid, have been reported. We observed in vitro and in vivo displacement
      of phenytoin by the antibiotics ceftriaxone, nafcillin, and sulfamethoxazole. In
      vitro studies demonstrated statistically significant (P less than 0.05) increases
      in free phenytoin after the addition of specific antibiotics to patients' sera
      and to phenytoin-supplemented sera from controls. Concentrations of free
      phenytoin in vivo, predicted by an equation we have found to be accurate for
      albumin concentrations greater than or equal to 32 g/L, were consistently
      underestimated in patients receiving concomitant therapy with the antibiotics
      studied. The concentrations of free phenytoin decreased towards the predicted
      values when the antibiotic therapy was discontinued. We conclude that
      ceftriaxone, nafcillin, and sulfamethoxazole can displace phenytoin from the
      usual protein carriers found in serum, in vitro and in vivo.

PMID- 1988218
TI  - T cell proliferative responses to molecular fractions of periodontopathic
      bacteria.
AB  - Soluble antigenic preparations of Veillonella parvula and Bacteroides gingivalis
      were separated by SDS-PAGE and used after electroblotting and solubilization for
      in vitro lymphocyte stimulation in 13 patients with severe periodontitis and 12
      controls. The cellular responses of controls and patients to V. parvula antigens
      were represented by four main proliferation-inducing fractions with 74-66, 52-46,
      22-19 and 12 kD mol. wt. These fractions induced slightly enhanced DNA synthesis
      in lymphocytes from eight patients who failed to respond to whole antigenic
      extract. Lymphocyte samples from Veillonella whole extract unresponsive patients
      were also examined for in vitro proliferation by B. gingivalis fractions. Almost
      all stimulatory activities could be classified into five regions of 84-74, 35-31,
      28-25, 17-15 and 12 kD.

PMID- 1988220
TI  - A new murine model of autoimmune orchitis induced by immunization with viable
      syngeneic testicular germ cells alone. I. Immunological and histological studies.
AB  - Experimental autoimmune orchitis (EAO) was produced in C3H/He mice with as high
      as 100% incidence by two or three s.c. injections of 1 x 10(7) viable syngeneic
      testicular germ cells (TC) without resorting to adjuvants, Bordetella pertussis
      vaccine, or other immunological manipulations. On day 40 after the first
      injection of TC, the lesions induced were characterized by interstitial
      infiltration of inflammatory cells and severe hypospermatogenesis in the testis
      with resulting whole organ atrophy and, in contrast, by a complete lack of
      epididymitis. Immunological studies revealed that this form of immunization
      caused both delayed-type hypersensitivity and humoral antibody responses to
      syngeneic TC. We compared the susceptibilities to the induction of this type of
      EAO among six different strains of inbred mice comprising A/J, AKR, BALB/c,
      C3H/He, C57BL/6 and DBA/2 mice. All strains except for DBA/2 mice developed
      lesions of EAO to a greater or lesser extent, and severe disease was induced with
      high frequency in two strains, C3H/He and A/J. As this murine model of EAO can be
      induced without the use of Freund's complete adjuvant and B. pertussis vaccine,
      it is simply 'autoimmune' in nature and may provide new ways for further
      investigation into the immunological mechanisms which regulate deleterious
      autoimmune reactions to germ cell antigens leading to the male infertility.

PMID- 1988219
TI  - Anti-idiotype and immunosuppressant treatment of murine lupus.
AB  - The effect of the administration of a xenogeneic anti-idiotype antibody (anti
      Id33) to a cross-reactive idiotype (Id33) present on anti-dsDNA antibody was
      examined in 6-week-old (NZB/NZW) F1 (BWF1) female mice. The administration of
      anti-Id33 led to a transient reduction in immunoglobulins expressing Id33,
      followed by a rise at 30 and 34 weeks that was significantly higher than in
      untreated mice (P less than 0.05). Likewise, anti-dsDNA antibody levels were
      significantly higher at 10 and 18 weeks than in untreated mice (P less than
      0.01). No differences were seen in survival to 40 weeks, proteinuria or the
      severity of glomerulonephritis. Concurrent administration of cyclosporin A (CyA)
      with anti-Id33 markedly ameliorated glomerular injury and proteinuria and
      improved survival. By contrast, glomerular injury, proteinuria and survival were
      worse in mice treated with cyclophosphamide plus anti-Id33, compared with
      untreated mice. Neither CyA nor cyclophosphamide treatment, when given with anti
      Id33 altered serum levels of anti-dsDNA, anti-ssDNA or Id33+ immunoglobin,
      compared with untreated mice. The different effects of CyA and cyclophosphamide
      on T lymphocytes and their discrepant effects on glomerular injury when given
      with anti-Id33 in this model lead us to postulate a role for T lymphocytes in the
      glomerular injury of BWF1 lupus.

PMID- 1988221
TI  - Formation of subepithelial dense deposits in rats induced by a monoclonal
      antibody against the glomerular cell surface antigen.
AB  - We developed a monoclonal antibody, H5H3, of IgG1 subclass by hybridization
      technique using spleen cells of mice immunized with plasma membrane fraction of
      isolated rat glomeruli. H5H3 recognized main bands at about 220 kD by immuno
      overlay technique and bound to the glomerulus as well as brush border of proximal
      tubules by indirect immunofluorescence (IF) microscopy on normal rat kidney
      frozen sections. By immunoelectron microscopy (IEM) it bound to the surface of
      mainly glomerular epithelial cell and weakly to the endothelial cell. After
      injection to Wistar rats it remained granularly in the glomerulus for more than 2
      weeks seen by IF. When rats were preimmunized with murine IgG 4 days before the
      injection of H5H3, mouse IgG, rat IgG and C3 were strongly visible granularly in
      the glomerulus in 14 days by IF. Numerous dense deposits were formed at
      subepithelial area seen by transmission electron microscopy. Perfusion experiment
      of H5H3 into rat left kidney showed granular distribution of mouse IgG in 48 h,
      indicating that the reaction occurred in situ. H5H3 bound diffusely in fine
      granular pattern on the surface of cultured glomerular epithelial cells (GEC)
      studied by IF and IEM. Antigenic redistribution occurred on GEC after incubation
      of H5H3 at 37 C. These results suggested the required conditions to form
      subepithelial immune dense deposits, namely that H5H3 after reaction with antigen
      could stay for long time in the glomerulus; that H5H3 became an antigen in
      autologous phase to induce large immune complexes; and H5H3 could induce
      antigenic modulation.

PMID- 1988222
TI  - Recombinant interleukin-1 alpha inhibits the growth of rat mesangial cells in
      culture.
AB  - We have investigated the effect of interleukin-1 (IL-1) on the growth of
      mesangial cells isolated from rat kidney. Recombinant IL-1 alpha inhibited 3H
      thymidine uptake by mesangial cells in a dose-dependent manner in the presence of
      either 0.5% or 5% fetal bovine serum (FBS). In the presence of high concentration
      of FBS (10%), the effect of IL-1 was not prominent. The inhibitory effect of IL-1
      on the growth of mesangial cells was also confirmed by a change in cell numbers
      and measurements of protein synthesis with 3H-leucine. IL-1-induced inhibition of
      mesangial cell growth was not affected by indomethacin. IL-1 showed no effects on
      intracellular Ca2+ levels in mesangial cells. These observations indicate that IL
      1 inhibits the growth of mesangial cells, and thus may play a protective role for
      mesangial cells from abnormal proliferation in some pathophysiological states.

PMID- 1988223
TI  - Lactoferrin-inducible monocyte cytotoxicity for K562 cells and decay of natural
      killer lymphocyte cytotoxicity.
AB  - Monocyte-enriched and lymphocyte-enriched fractions of peripheral blood from
      three healthy volunteers were obtained by percoll density gradient
      centrifugation. The cytotoxic activity of each fraction against 51Cr-labelled
      K562 cells was quantified in a 2-h assay using freshly isolated cells of each
      fraction and cells of each fraction which had been incubated with and without
      lactoferrin in complete medium for 18 h before performing the assay. We have
      thereby shown that cytotoxicity was not demonstrable in the lymphocyte fraction
      (containing 7.3 +/- 2% large granular lymphocytes) after 18 h in medium, whereas
      the cytotoxicity of the monocyte fraction (containing 3 +/- 0.4% large granular
      lymphocytes) was still significantly increased (P less than or equal to 0.01) and
      that lactoferrin had no effect on lymphocyte fraction cytotoxicity while
      producing an 11-fold increase in the cytotoxicity of the monocyte fraction. It is
      therefore possible to perform a relatively simple test of monocyte cytotoxicity
      using lactoferrin as a stimulant in a 2-h 51Cr-labelled K562 assay system by
      allowing 18 h to elapse for lymphocyte natural killer cytotoxicity to decay.

PMID- 1988224
TI  - Human rib bone marrow mononuclear cells spontaneously synthesize and secrete IgE
      in vitro.
AB  - We have examined spontaneous secretion of IgE by human rib bone marrow
      mononuclear cells (MNC). Bone marrow MNC from nine out of 12 rib specimens
      synthesized and secreted substantial amounts of IgE during 14 days of in vitro
      culture. The 14-day supernatants from these bone marrow MNC contained a mean of
      2589 pg/ml of IgE (n = 12) with a maximum production of 15,408 pg/ml of IgE
      compared with small amounts of IgE (80-200 pg/ml) produced by similarly cultured
      normal and inflammatory bowel disease intestinal lamina propria MNC. Using two
      rib specimens, time-course studies revealed spontaneous secretion of IgE to be
      minimal during the first 2 days of culture (152 pg/ml), followed by a steady
      increase between days 4 (517 pg/ml) and 14 (3588 pg/ml). The addition of pokeweed
      mitogen resulted in 72% suppression of spontaneous IgE production by bone marrow
      MNC. The bone marrow MNC isolated from the ribs consisted of 22% Leu12+ (B) cells
      of which 3.2% were surface IgE positive. Staining for cytoplasmic immunoglobulin
      revealed 1% of the bone marrow MNC to be cytoplasmic IgE+. The presence of IgE
      bearing and IgE-secreting MNC in human bone marrow is consistent with the
      observation that allergen-specific IgE-mediated hypersensitivity is adoptively
      transferred by human bone marrow transplantation and demonstrates the usefulness
      of human bone marrow MNC for examination of IgE secretory and regulatory events.

PMID- 1988225
TI  - Immunoglobulin and cytokine production by neonatal lymphocytes.
AB  - Growth and differentiation of cord blood B cells were studied using T cell
      depleted populations. In the absence of in vitro activation, cord blood B cells
      proliferated in response to cytokines including interleukin-2 (IL-2) and
      interleukin-4 (IL-4); anti-mu-stimulated cord B cells had a lesser response to IL
      2 than adult cells. IgM synthesis by cord blood B cells was enhanced by
      interleukin-6 (IL-6) and decreased by IL-2. In cultures activated by
      Staphylococcus aureus Cowan I (SAC), cord blood B cells produced lesser increases
      in IgM than adult B cells regardless of the cytokine added. Cord blood B cells
      produced no IgG or IgA with any cytokine preparation with or without SAC
      activation. Supernatants of cord blood T cells pulse-stimulated with
      phytohaemagglutinin and phorbol myristate acetate contained less IL-2 and IL-6
      and had less growth and differentiation activity than adult T cell supernatants.
      The results confirm a limited cord blood B cell response and also suggest a
      limitation in production of B cell stimulatory lymphokines by cord blood T cells.

PMID- 1988227
TI  - Production by cultured human monocytes of mesangial cell proliferation factor(s)
      differing from interleukin-1 and interleukin-6.
AB  - Conditioned media from human peripheral blood leucocytes treated with
      lipopolysaccharide (LPS) induced a marked increase in the 3H-thymidine
      incorporation of cultured mesangial cells at low serum concentration (four to six
      times higher than control). Two sizes (100-70 and 8-12 kD) of monocyte-derived
      mesangial cell proliferating factors (MDF) were separated by column
      chromatography. Their peaks were distinct from those of thymocyte proliferating
      activity. The addition of anti-human interleukin-1 (IL-1) or anti-recombinant
      human interleukin-6 (IL-6) antibody to the fractionated MDF failed to have any
      effect on the mitogenic activity toward mesangial cells. The addition of anti
      human platelet-derived growth factor (PDGF) antibody to the low molecular weight
      fraction decreased mesangial cell mitogenic activity (40-60% of control), but
      addition to the higher fraction did not (80-100% of control). From these data it
      seems that a large portion of the monocyte-derived mesangial cell growth factor
      was not comprised of IL-1 or IL-6 but of PDGF-like molecules; and that there is
      an unknown mesangial cell proliferating factor (or factors) besides IL-1, IL-6
      and PDGF.

PMID- 1988226
TI  - Isotype distribution of mucosal IgG-producing cells in patients with various IgG
      subclass deficiencies.
AB  - The subclass distribution of IgG-producing immunocytes was examined by
      immunohistochemistry in nasal and rectal mucosa of infection-prone patients with
      untreated IgG subclass deficiencies. Biopsy specimens from the two sites were
      obtained in 18 clinically and serologically well-characterized adult subjects;
      only a nasal or rectal sample was available from nine similar patients. Chronic
      lung disease was common in the patient groups with selective serum IgG1
      deficiency and combined IgG1 and IgG3 deficiency, whereas the other categories of
      patients had mainly upper airway and other mild infections. Serum IgG2 or IgG3
      deficiency was usually expressed also at the cellular level in rectal mucosa, and
      the proportion of rectal IgG1 cells was significantly correlated with the IgG1
      level (r = 0.90, P less than 0.001). Likewise, there tended to be a decreased
      expression of the actual subclass at the cellular level in nasal mucosa of
      patients with serum IgG1 or IgG2 deficiency. Conversely, the median nasal
      proportion of IgG3 cells was remarkably unaffected by a deficiency of this
      subclass in serum and rectal mucosa. Interestingly, these patients rather tended
      to have raised IgG3 and reduced IgG2 cell proportions in their nasal mucosa,
      although this apparent local IgG3 compensation was nevertheless strongly
      correlated with the serum IgG3 level (r = 0.87, P less than 0.002). These
      disparities may reflect different antigenic and mitogenic exposure of the two
      tissue sites; for example, a persistent protein bombardment of the nasal mucosa
      that could conceivably override locally a B cell maturation defect. The possible
      clinical consequences of such variable mucosal expression of IgG subclass
      deficiencies remain to be studied.

PMID- 1988228
TI  - Measurement of interleukin-6 in bronchoalveolar lavage fluid by radioimmunoassay:
      differences between patients with interstitial lung disease and control subjects.
AB  - Bronchoalveolar lavage fluid (BALF) from subjects with a variety of interstitial
      lung diseases (active sarcoidosis, pigeon breeders' disease (PBD), asymptomatic
      pigeon breeders, patients with idiopathic pulmonary fibrosis) and from control
      subjects were assayed for interleukin-6 (IL-6) using a novel radioimmunoassay
      system. IL-6 was detectable in BALF from all groups, with disease groups showing
      significantly increased IL-6 levels compared with controls (P less than 0.01 in
      all cases). When these results were standardized, using urea to compensate for
      dilution effects in the BALF, only the asymptomatic pigeon breeders had
      significantly higher IL-6 levels than the controls (P less than 0.025), with all
      other groups showing no difference. When albumin was used for standardization,
      both the PBD group (P less than 0.001) and the sarcoidosis patients (P less than
      0.01) had considerably lower levels of IL-6 than the control subjects. Using
      either albumin or urea for standardization, the PBD patients had significantly
      lower levels of IL-6 than do their asymptomatic counterparts (P less than 0.001
      in both cases). This is contrasted by the finding of greatly elevated levels of
      IgG in the BALF of the PBD patients compared with asymptomatics (P less than
      0.001). There was, however, no relation between IL-6 and IgG in any patient
      group, although the PBD patients had the lowest IL-6 and highest IgG as a group.
      These findings may suggest a mechanism by which asymptomatic subjects remain free
      from clinical complaints.

PMID- 1988229
TI  - Immunogenicity of surfactant. I. Human alveolar surfactant.
AB  - The immunogenicity of lung surfactant derived from amniotic fluid has been well
      established. We have set out to examine the antigenic similarity of human
      surfactant to non-human alveolar surfactants currently being used therapeutically
      in clinical trials with neonatal respiratory distress syndrome. To this end, we
      raised a series of eight monoclonal antibodies in rats directed to human
      surfactant (H1 to H8). All antibodies bound human surfactant as measured by
      ELISA. Four of these monoclonal antibodies bound surfactant components by Western
      blot analysis: all bound a 9-10-kD species. In addition, one antibody (H2) bound
      a protein of 16 kD, one (H8) a 6-kD protein, and one (H6) a 30-kD protein. When
      mixed with surfactant, three antibodies, H4, H7 and H8, profoundly altered
      surfactant activity in vitro in the pulsating bubble surfactometer. Three other
      antibodies, H1, H2, and H5 moderately inhibited surfactant's surface activity. We
      also examined the cross-reactivity of these monoclonal antibodies with bovine
      (CLSE) and porcine (Curosurf) surfactants. By Western blot analysis, only H6
      bound these heterologous surfactants. Other antibodies did so by ELISA. However,
      functional assays indicated that antibodies H7, H8 and H4 all greatly inhibited
      CLSE surface activity in vitro. Five antibodies (H1-H4 and H8) inhibited Curosurf
      function. Thus, human surfactant species, especially low molecular weight
      species, are highly antigenic. Antibodies to alveolar surfactants may inhibit
      surfactant function in vitro. As indicated by Western blot and cross-inhibition
      data, human lower molecular weight surfactants share epitopes with proteins from
      therapeutically important porcine and bovine surfactants. The potential
      importance of these findings to treatment of neonatal respiratory distress
      syndrome with heterologous surfactants is discussed.

PMID- 1988230
TI  - Evidence that X-linked severe combined immunodeficiency is not a differentiation
      defect of T lymphocytes.
AB  - In order to gain information about the nature of the defect in X-linked severe
      combined immunodeficiency (XSCID), we investigated gene expression in different
      lymphoid and haematopoietic cells of female carriers by looking for non-random X
      chromosome usage. We have shown non-random X chromosome usage in T lymphocyte
      enriched (E+) fraction in all carriers. E- cells and monocytes showed non-random
      X chromosome usage in three carriers tested. In the B cell series one carrier
      showed non-random inactivation in all EBV lines tested (10) and the same X
      chromosome was shown to be active in all cells. In other carriers there was a
      preference for use of the normal X chromosome but some B cell lines used the
      mutant X as well as the normal X. Similar results were found with granulocytes.
      In two female carriers DNA made directly from whole blood showed a non-random
      pattern of X chromosome usage. In fibroblast cultures from two female carriers
      more cells had the normal gene on the active X chromosome than had the defective
      gene on the active X chromosome. Within families there was heterogeneous
      expression of the gene. The gene that is defective in XSCID is expressed in all
      the cell types studied and, therefore, is not a T lymphocyte differentiation
      gene. The results are consistent with the gene being in a metabolic pathway as in
      certain autosomal recessive forms of SCID i.e. adenosine deaminase deficiency and
      purine nucleoside phosphorylase deficiency.

PMID- 1988232
TI  - Human cartilage is degraded by rheumatoid arthritis synovial fluid but not by
      recombinant cytokines in vitro.
AB  - Rheumatoid arthritis (RA) synovial fluid (SF) stimulated significant loss of
      glycosaminoglycans (GAG) from normal and pathological human cartilage biopsies
      over 2 days as compared with normal human serum. By contrast, 15 RA SFs failed to
      degrade killed normal cartilage, and degraded killed RA cartilage less
      effectively than living RA cartilage. Four RA SFs were treated with neutralizing
      anti-cytokine antisera prior to incubation with normal cartilage. The degrading
      effects of two of the fluids were reversed by anti-interleukin-1 alpha (IL-1
      alpha) while degradation by the third and fourth fluids were reversed by anti
      interleukin-1 beta (IL-1 beta) and anti-tumour necrosis factor-alpha (TNF-alpha),
      respectively. However, recombinant human IL-1 alpha, IL-1 beta, TNF alpha or a
      combination of all three cytokines had no degrading effect in this 2-day culture
      system. It is concluded that RA SF degrades cartilage by a mechanism involving a
      synergistic interaction between cytokines and some other component of SF.

PMID- 1988231
TI  - Immunogenicity of surfactant. II. Porcine and bovine surfactants.
AB  - Protein-containing surfactants of human and animal origin are being used
      increasingly to treat neonatal and adult respiratory distress syndromes. This
      trend led us to examine the antigenicity of two important preparations of animal
      surfactant, cow lung surfactant extract (CLSE) and a porcine surfactant
      preparation, Curosurf. We describe here 15 monoclonal antibodies against Curosurf
      and four against CLSE. Antibodies were studied by Western blot analysis to
      determine their ability to recognize protein components of their respective
      surfactant preparations. They were also tested for their ability to inactivate
      surfactant in vitro, assayed using the pulsating bubble surfactometer. Several
      antibodies directed against CLSE or Curosurf functionally inactivate the
      surfactant to which they were raised. We determined the degree of immunologic
      cross-reactivity between antibodies directed to CLSE and Curosurf against the
      other surfactant and also against human surfactant, both by Western blot and by
      examining functional inactivation in vitro. Antibodies to these animal
      surfactants that are commonly used therapeutically may inactivate the specific
      animal surfactant to which they were raised, as well as human and other
      surfactants. Generally, when antibodies inactivate surfactant from more than one
      animal species, they inactivate heterologous surfactants comparably to the extent
      to which they inactivate the surfactant to which they are directed. Immune
      complexes between anti-surfactant antibodies and surfactant have been described
      in the course of neonatal respiratory distress syndrome. The potential
      pathophysiological importance of anti-surfactant antibodies may therefore lie in
      their ability to inactivate administered surfactant, other similar surfactants
      and endogenous surfactant. In so doing, these antibodies may potentiate
      surfactant deficiency or pulmonary injury initiated by other stimuli.

PMID- 1988233
TI  - 14C1, an antigen associated with human ovarian cancer, defined using a human IgG
      monoclonal antibody.
AB  - We have selected a human EBV-transformed cell line from the involved lymph nodes
      of an ovarian cancer patient which secretes an IgG1 kappa antibody, able to
      recognize an antigen present on the surface of ovarian cancer cells. The antigen,
      termed '14Cl,' has previously been shown by immunohistological techniques to be
      present on the surface of the malignant cells within tumour specimens. Western
      blotting analysis has shown that the majority of primary ovarian cancer specimens
      and three continuous cell lines derived therefrom express 14Cl; other tissue
      types were negative. Preliminary biochemical characterization has been carried
      out, which shows that the 14Cl antigen has a molecular weight range of 25-32 kD
      and an isoelectric point from pI 6.3 to 6.8. We believe that the 14Cl antigen is
      immunologically relevant to ovarian cancer patients and may therefore represent a
      novel target for both active and passive immunotherapy.

PMID- 1988234
TI  - Onset and duration: measurement and analysis.

PMID- 1988235
TI  - Prominence of slow acetylator phenotype among patients with sulfonamide
      hypersensitivity reactions.
AB  - Delayed hypersensitivity reactions are among the most severe adverse effects of
      the sulfonamides in current clinical use. These reactions appear to occur because
      of differences in the metabolism and detoxification of reactive metabolites of
      the sulfonamides. N-Acetylation is a major metabolic pathway for the
      sulfonamides. Slow acetylation phenotype might be a risk factor for the
      development of these reactions. We determined the acetylation phenotype of 21
      patients who had suffered hypersensitivity reactions to the sulfonamides. There
      were 11 females and 10 males in the group, with a mean age of 15 years (age
      range, 1.8 to 50 years). Their acetylator phenotype was determined by determining
      the ratio of urinary caffeine metabolites (1-methylxanthine to 5-amino-6
      formylmethyluracil after an oral dose of 50 mg caffeine). Nineteen (90%) of the
      patients were slow acetylators compared to a 55% incidence of slow acetylators in
      a race-matched control population (p less than 0.008). This suggests that a slow
      acetylator phenotype is a risk factor for the development of sulfonamide
      hypersensitivity reactions and provides further support for the role of
      imbalances in genetically determined pathways of metabolism and detoxification of
      the sulfonamides in the pathogenesis of these reactions.

PMID- 1988236
TI  - The mephenytoin oxidation polymorphism is partially responsible for the N
      demethylation of imipramine.
AB  - The metabolism of imipramine in six poor metabolizers of mephenytoin was compared
      with the metabolism of 16 extensive metabolizers of mephenytoin from an earlier
      study. Each subject was given single doses of 100 mg imipramine hydrochloride and
      100 mg desipramine hydrochloride on separate occasions. Imipramine demethylation
      clearance was 0.74 L.min-1 (mean; range, 0.31-1.24) in poor metabolizers of
      mephenytoin compared with 1.43 L.min-1 (mean; range, 0.61-3.81) in extensive
      metabolizers of mephenytoin (p = 0.01, Mann-Whitney U test). It has previously
      been shown that the imipramine clearance by way of other pathways and desipramine
      oral clearance, both largely representing 2-hydroxylation, are considerably lower
      in poor metabolizers of sparteine than in extensive metabolizers of sparteine. In
      contrast, five subjects who were poor metabolizers of mephenytoin and extensive
      metabolizers of sparteine and a control group of 11 subjects who were extensive
      metabolizers of mephenytoin and sparteine showed no statistically significant
      difference with regard to these parameters. One subject who was a poor
      metabolizer of mephenytoin and sparteine had the lowest imipramine oral clearance
      of all 22 subjects studied. In conclusion, this and an earlier study show that
      the oxidation of imipramine is mediated by means of two different polymorphic
      P450 isozymes, 2-hydroxylation by way of the sparteine oxygenase (P450IID6) and
      demethylation by way of the mephenytoin oxygenase (P450IIC8).

PMID- 1988237
TI  - Population dose versus response of betaxolol and atenolol: a comparison of
      potency and variability.
AB  - The dose-response curves of betaxolol and atenolol were compared in 140 patients
      with mild to moderate essential hypertension. Patients with a supine diastolic
      blood pressure of 95 to 115 mm Hg at the end of a 4-week single-blind placebo
      washout phase were randomized (double-blind) to receive either betaxolol or
      atenolol in a dose-escalation manner. The dose (5 mg, 10 mg, and 20 mg betaxolol;
      25 mg, 50 mg, and 100 mg atenolol) was increased if the supine diastolic blood
      pressure remained greater than 90 mm Hg after 4 weeks at each level. The final
      dose in the escalation phase was continued for an additional 12 weeks and then
      followed by a 2-week placebo phase. The data were analyzed with a population
      model using the program NONMEM (nonlinear mixed effects model). Atenolol
      exhibited a graded dose-response curve, whereas the lowest dose of betaxolol
      produced maximum or near-maximum effect. The estimated maximum effect (drug plus
      possibly unmeasured placebo effect) was similar for both treatments, about 13 mm
      Hg (95% confidence interval, 10 to 15 mm Hg). A trend toward less interindividual
      variability (coefficient of variation) was apparent for betaxolol compared to
      atenolol, 19% (95% confidence interval, 0% to 29%) versus 31% (95% confidence
      interval, 0% to 47%). The intraindividual variability (standard deviation) in
      supine diastolic blood pressure, 5.9 mm Hg (95% confidence interval, 5.2 to 6.5
      mm Hg), did not differ significantly between drugs despite significantly greater
      intraindividual variability (coefficient of variation) in atenolol
      concentrations, 62% (95% confidence interval, 48% to 73%) versus 26% (95%
      confidence interval, 22% to 29%) for betaxolol.

PMID- 1988238
TI  - Cimetidine alters the disposition kinetics of the monoamine oxidase-A inhibitor
      moclobemide.
AB  - The influence of cimetidine on the absorption and disposition of moclobemide was
      examined in eight healthy male subjects. A single 100 mg intravenous and 100 mg
      oral dose of moclobemide was administered before and after 2 weeks of cimetidine
      administration (200 mg five times a day). The data on intravenous administration
      indicated that cimetidine produced a statistically significant alteration in the
      following disposition parameters (mean values for control versus cimetidine):
      systemic clearance, 46.6 versus 28.3 L/hr; mean residence time, 2.1 versus 3.2
      hours; elimination half-life, 1.6 versus 2.3 hours. There was no significant
      difference in the steady-state volume of distribution. The absolute oral
      bioavailability of moclobemide increased significantly after cimetidine
      administration (54% versus 68%), as did the maximum plasma concentration after a
      single oral dose (575 versus 787 ng/ml). There were no differences in the mean
      absorption time or time to achieve maximum concentration. The values of systemic
      and apparent oral clearances of moclobemide after cimetidine administration were
      directly related to the corresponding control values before cimetidine. In
      contrast, the percentage change in clearance was essentially independent of the
      corresponding initial control clearance value.

PMID- 1988239
TI  - Enhancement of absorption and effect of glipizide by magnesium hydroxide.
AB  - The effects of magnesium hydroxide on the pharmacokinetics and pharmacodynamics
      of glipizide were studied in eight healthy volunteers in a randomized crossover
      trial. After an overnight fast, 5 mg glipizide was given with either 150 ml water
      or water containing 850 mg magnesium hydroxide. Magnesium hydroxide increased the
      areas under the plasma glipizide concentration-time curves (AUC) from 0 to 1/2
      hour and from 0 to 1 hour by 180% (p less than 0.05) and 69% (p less than 0.05),
      respectively. The peak plasma concentration, time to peak, total AUC, elimination
      half-life, and mean residence time of glipizide remained unchanged. The
      incremental plasma insulin area from 0 to 1/2 hour increased by 85% (p less than
      0.05), and the time to maximal insulin response was reduced (p less than 0.05)
      during the magnesium hydroxide phase. The corresponding decremental plasma
      glucose area increased fourfold (p less than 0.05), and the maximal glucose
      decrease was 35% greater (p less than 0.05) than during the control phase. We
      conclude that the concomitant ingestion of magnesium hydroxide and glipizide may
      result in accelerated absorption of glipizide and increased early insulin and
      glucose responses.

PMID- 1988240
TI  - Caffeine as a metabolic probe: exploration of the enzyme-inducing effect of
      cigarette smoking.
AB  - It has been realized recently that the primary metabolism of caffeine in humans
      is catalyzed by P-450IA2 and that the rate of caffeine metabolism can be
      estimated from a metabolic ratio in a single urine sample. A population of 178
      students including 19 smokers were subjected to this caffeine test to establish
      their P-450IA2 index. Both stated numbers of cigarettes smoked per day and
      urinary cotinine levels as a confirmatory measure correlated significantly with
      enzyme activity showing dose-effect relationships (r = 0.62 and 0.89,
      respectively). Nevertheless, more nonsmokers than smokers had the highest enzyme
      indexes, suggesting that dietary elements or other factors may determine P-450IA2
      activities in populations. Because P-450IA2 is a monooxygenase that may be
      confined to the liver, caffeine reveals directly the Ah-receptor-dependent enzyme
      induction only in the liver, but it may also be a signal of induction elsewhere.

PMID- 1988242
TI  - Efficacy and tolerance of the new class IB antiarrhythmic barucainide: an
      intravenous dose-finding study.
AB  - Barucainide is a new class IB antiarrhythmic agent that was studied for efficacy
      and safety after intravenous administration in patients with severe ventricular
      arrhythmias. All patients received 80 mg/hr barucainide intravenously for 7 hours
      or until ventricular arrhythmias were suppressed by greater than 90%. In
      responders a maintenance dose was given for 24 hours, aimed to achieve steady
      state conditions. At baseline and during the treatment and washout periods 24
      hour Holter recordings were performed. In addition, electrocardiogram, blood
      pressure, and plasma concentration of barucainide were measured. In 9 of 12
      patients dose titration was effective (mean dose, 185 mg). In six of nine
      patients arrhythmia suppression persisted during maintenance therapy (mean dose,
      18 mg/hr). Plasma concentrations correlated with given doses, rather than with
      antiarrhythmic efficacy. During the washout period, five patients required more
      than 12 hours for recurrence of arrhythmias. Treatment was stopped in one patient
      because of proarrhythmia; one patient had moderate heat sensations. Thus
      barucainide is a potent class IB agent, with a favorable side effect profile.

PMID- 1988241
TI  - Effect of steroids on cerebrospinal fluid penetration of antituberculous drugs in
      tuberculous meningitis.
AB  - Sixteen patients with oral isoniazid, pyrazinamide, rifampin, and intramuscular
      streptomycin for tuberculous meningitis were studied. The concentrations of
      isoniazid, pyrazinamide, rifampin, and streptomycin in cerebrospinal fluid (CSF)
      obtained 3 hours after administration were 2.40, 34.78, 0.29, and 3.78
      micrograms/ml, respectively. The CSF concentrations of isoniazid and pyrazinamide
      were well above the minimum inhibitory concentration for Mycobacterium
      tuberculosis. Concentrations of rifampin and streptomycin were above the minimal
      inhibitory concentration initially but declined below the minimal inhibitory
      concentration at later times. The CSF penetration of isoniazid, pyrazinamide,
      rifampin, and streptomycin was about 89%, 91%, 5%, and 20%, respectively. In
      eight patients who received antituberculous drugs in combination with steroids,
      the mean CSF and serum concentrations, as well as CSF/serum ratios at various
      intervals of treatment, were not statistically different (p greater than 0.05)
      from those of the eight patients who did not receive steroids.

PMID- 1988243
TI  - Kinetic therapy: adjunct to conventional treatment of anasarca.

PMID- 1988244
TI  - Myocardial infarction.

PMID- 1988245
TI  - Critical care nurses and ethical dilemmas.

PMID- 1988246
TI  - The right to die and the living will: Missouri status.

PMID- 1988247
TI  - Spiritual distress and critical illness.

PMID- 1988248
TI  - Albumin overview: use as a nutritional marker and as a therapeutic intervention.

PMID- 1988249
TI  - Critical illness and intensive care: what it means to the client.
AB  - How do people make sense of critical illness and the ICU? What does that
      experience mean to the patient? These questions are of vital importance in
      selecting nursing interventions that are appropriate as well as therapeutic. The
      study of individuals and their experiences can provide a rich and unexpected
      picture of what it is like to live through a critical illness. This information
      can increase our understanding of the needs of critically ill patients as well as
      how people in general make sense of their world.

PMID- 1988250
TI  - The concept of stigma: timely, relevant, and possibly uncomfortable.

PMID- 1988251
TI  - Something new for Critical Care Nurse.

PMID- 1988252
TI  - Collaboration: a right and responsibility of professional practice.

PMID- 1988253
TI  - Reye's syndrome in adults.

PMID- 1988255
TI  - Modulation of gastric pH by continuous gastric and jejunal infusion of
      cimetidine.
AB  - We studied the effect of gastric versus jejunal tube feedings on gastric pH and
      evaluated the acid-inhibiting effects of continuous gastric and jejunal infusions
      of cimetidine. pH was monitored by an intragastric pH probe in 19 gastrostomy and
      13 jejunostomy patients during fasting, continuous infusions of Osmolyte,
      cimetidine, and simultaneously Osmolyte and cimetidine. Gastric Osmolyte
      increased fasting pH from a mean of 1.32 to 2.78 (P less than 0.01), while
      jejunal Osmolyte did not (pH 1.02). Continuous gastric infusion of cimetidine
      maintained a high gastric pH (5.06) in 17 of 19 patients. Jejunal cimetidine also
      achieved therapeutic serum levels and raised gastric pH to 4.81 in nine of 13
      patients. We conclude that the persistently low gastric pH during jejunostomy
      tube feeding may play a major role in the upper gastrointestinal bleeding
      previously observed in such patients and that continuous gastric and jejunal
      cimetidine infusions effectively raise and sustain a high gastric pH.

PMID- 1988254
TI  - Omeprazole. Gastrin and gastric endocrine cell data from clinical studies.
AB  - Gastric enterochromaffin-like cell carcinoids have been detected in rats exposed
      lifelong to omeprazole. By inhibiting acid secretion, omeprazole causes
      hypergastrinemia which, with prolonged exposure, exerts a trophic effect on
      enterochromaffin-like cells with eventual enterochromaffin-like cell carcinoid
      formation in some animals. This mechanism seems to explain the appearance of
      enterochromaffin-like cell carcinoids in human hypergastrinemic states, whether
      associated with hyperchlorhydria, eg, Zollinger-Ellison syndrome, or with
      hypochlorhydria, eg, pernicious anemia (nonantral atrophic gastritis). Omeprazole
      produces modest serum gastrin elevations in humans when monitored over a 24-hr
      period. Gastrin levels are markedly lower and less sustained than in the above
      hypergastrinemic states. Extensive gastric biopsy data from patients enrolled in
      long-term studies indicate that omeprazole administration is not associated with
      clinically significant changes in the human oxyntic endocrine cell population.
      Man and rat differ markedly both in their gastrin response to a given level of
      acid inhibition and in their response to the trophic influence of gastrin on
      enterochromaffin-like cells. The rat model is a false indicator of risk in man.

PMID- 1988256
TI  - Prevalence of Helicobacter pylori in specific forms of gastritis. Further
      evidence supporting a pathogenic role for H. pylori in chronic nonspecific
      gastritis.
AB  - Helicobacter pylori colonization of the gastric mucosa is strongly associated
      with chronic nonspecific gastritis; moreover, there is evidence to suggest that
      H. pylori may cause this form of gastritis. However, there is little or no
      information on the prevalence of H. pylori in specific forms of gastritis. Our
      hypothesis was that if H. pylori was pathogenic in chronic nonspecific gastritis,
      organisms would be found frequently in this type of gastritis but infrequently in
      specific forms of gastritis. Prevalence rates of H. pylori were determined
      independently in patients with eosinophilic and Crohn's gastritis, Menetrier's
      disease, and chronic nonspecific gastritis. The prevalence of H. pylori in
      patients with chronic nonspecific gastritis was 71%, whereas the organism was not
      identified in patients with any form of specific gastritis. This finding further
      supports the accumulating evidence that H. pylori is a primary pathogenic factor
      in chronic nonspecific gastritis.

PMID- 1988257
TI  - Gastric emptying of indigestible tablets in relation to composition and time of
      ingestion of meals studied by metal detector.
AB  - Enteric-coated tablets leave the stomach mainly during the interdigestive phase.
      Composition as well as time of ingestion of meals may influence their gastric
      emptying considerably. In 12 normal volunteers gastric emptying of a plastic
      tablet with a metal core was followed by a metal detector in relation to
      different compositions and various times of ingestion of meals. With an empty
      stomach and after ingestion of 250 ml water, the mean time for gastric emptying
      of the tablet was 38 +/- 11 min (mean +/- SEM) and 38 +/- 8 min. Two hundred
      fifty milliliters of milk (652 kJ) and a formula diet (1000 kJ) delayed gastric
      emptying time to 128 +/- 14 and 152 +/- 6 min, respectively (P less than 0.05).
      Breakfast (2200 kJ) further retarded gastric emptying compared with both liquids
      to 249 +/- 24 min (P less than 0.05). There was a close correlation between
      nutritive density and gastric emptying of the tablet (r = 0.92; P less than
      0.001). Main meals also delayed gastric emptying of tablets when compared to
      empty stomach (P less than 0.05). A snack after breakfast further delayed gastric
      emptying from 201 +/- 10 to 278 +/- 19 min (P less than 0.05). The largest delay
      was observed following ingestion of breakfast, lunch, dinner, and additional
      snacks (509 +/- 220 min). We conclude that the delay of gastric emptying of
      enteric-coated tablets by food is related to its nutritive density and eating
      habits. The gastric emptying of an enteric coated tablet that is ingested early
      in the morning may be delayed until late at night when several meals and snacks
      are ingested during the day, leading to unwanted alterations in bioavailability
      and to possible adverse effects.

PMID- 1988258
TI  - Persistence of chronic constipation in children after biofeedback treatment.
AB  - We investigated the efficacy of biofeedback treatment and evaluated anorectal
      factors that might be responsible for persistence of chronic constipation with or
      without encopresis in a group of 38 children with abnormal contraction of the
      pelvic floor during straining and persistence of chronic constipation with
      encopresis after conventional treatment. Nine children were unsuccessful in
      learning to relax the pelvic floor during straining with biofeedback treatment,
      and one patient had contraction of the pelvic floor on follow-up despite
      successful biofeedback treatment; none recovered. Twenty-eight children were able
      to relax the pelvic floor on follow-up; 14 recovered and 14 did not recover from
      chronic constipation. Nonrecovered patients who learned to relax the pelvic floor
      had significantly decreased rectal and anal responsiveness to rectal distension
      as compared to recovered patients during the initial and follow-up anorectal
      manometric study. Psychological factors such as social competence and behavior
      problems did not appear to be responsible for recovery or nonrecovery from
      chronic constipation and encopresis.

PMID- 1988259
TI  - Clinical and physiological study of anal sphincter and ileal J pouch before
      preileostomy closure and 6 and 12 months after closure of loop ileostomy.
AB  - Spontaneous evolution of pouch and anal function, and absorption features has
      been assessed in 15 patients who underwent proctocolectomy with J ileal pouch
      anastomosis without conservation of a rectal muscular cuff. All the patients were
      studied before preileostomy closure and six and 12 months after the closure of
      the protection loop ileostomy. Stool frequency was identical at six and 12 months
      (mean +/- SEM: 5.0 +/- 0.4 and 5.3 +/- 0.5/day, respectively). Sixty-six percent
      of patients at six months and 40% of patients at 12 months need to defecate at
      least one time during night. Stool weight as well as steatorrhea decreased
      significantly six months after the closure of loop ileostomy (P less than 0.05).
      Mean resting anal pressure remained unchanged six and 12 months after closure of
      the loop ileostomy (41 +/- 6 and 45 +/- 5 cm H2O, respectively). Maximum squeeze
      anal pressures increased significantly at six (P less than 0.05) and 12 months (P
      less than 0.05). The rectoanal inhibitory reflex was always absent at the same
      period. The maximum pouch capacity increased significantly during the first six
      months (P less than 0.01) from 142 +/- 17 to 279 +/- 27 ml. The maximum infused
      volume during a saline continence test was not significantly different at six and
      12 months; the percentage of evacuation of the reservoir and the volume at which
      the first ileal contraction appeared in the reservoir increased significantly (P
      less than 0.05) at six and 12 months. In conclusion, in patients with ileoanal
      anastomosis and pouch reservoir, the closure of the loop ileostomy is associated
      with spontaneous modifications of the anal and pouch parameters.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1988260
TI  - Effect of 5-hydroxytryptamine and its antagonists on colonic smooth muscle of the
      rabbit.
AB  - The effect of 5-hydroxytryptamine (5HT) was studied in circular and longitudinal
      muscle from the proximal and distal colon of New Zealand white rabbits. 5HT
      stimulated a dose-dependent isometric contraction of distal and proximal circular
      muscle that was greater than in distal longitudinal muscle (P less than 0.01).
      5HT did not stimulate taenia coli longitudinal muscle. The EC50 for 5HT
      stimulation of distal circular muscle (-7.0 +/- 0.1), distal longitudinal muscle,
      and proximal circular muscle was similar. Methysergide dose-dependently inhibited
      the 5HT stimulation of both proximal and distal circular muscle. The IC50 for
      methysergide inhibition of 5HT (5 x 10(-7) M) stimulation was -5.5 +/- 0.2.
      Ketanserine and ICS 205-930 did not inhibit 5HT stimulation of colonic muscle.
      Tetrodotoxin (TTX) decreased the potency, but not the efficacy of 5HT stimulation
      of proximal and distal circular muscle. Atropine decreased the potency (EC50 = 
      6.6 +/- 0.1) (P less than 0.05) and the efficacy by 40%. Electrical field
      stimulation (EFS) caused an on-contraction and off-contraction of distal circular
      muscle and an on-contraction of proximal circular muscle. 5HT decreased the off
      contraction of the distal circular muscle but did not affect the on-contraction
      of the other muscle strips. 5HT receptor antagonists did not affect EFS of the
      tissue. The studies suggest: (1) 5HT stimulates circular colonic muscle with
      greater efficacy than longitudinal muscle, (2) 5HT stimulates circular muscle
      through a 5HT1 receptor, (3) there is atropine-sensitive and atropine-insensitive
      5HT stimulation of circular colonic muscle, (4) 5HT inhibits neurons responsible
      for the off-contraction in distal circular muscle without affecting the on
      contraction.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1988261
TI  - Rectal irrigation with short-chain fatty acids for distal ulcerative colitis.
      Preliminary report.
AB  - Colon cells from patients with ulcerative colitis utilize short-chain fatty acids
      inefficiently and may be exposed to decreased concentrations of these compounds.
      To test whether irrigation of the inflamed mucosa with short-chain fatty acids is
      useful, we conducted a six-week preliminary trial in 12 patients with distal
      colitis. Each patient used twice daily rectal irrigations with 100 ml of a
      solution containing acetate (80 mM), propionate (30 mM), and butyrate (40 mM).
      Two patients stopped at three weeks, one because of no improvement and the other
      because of complete resolution of symptoms. Of the 10 who completed the trial,
      nine were judged to be at least much improved and showed a change in a mean
      disease activity index score from 7.9 +/- 0.3 (SE) to 1.8 +/- 0.6 (SE) (P less
      than or equal to 0.002) and in a mucosal histology score from 7.7 +/- 0.7 (SE) to
      2.6 +/- 0.7 (SE) (P less than or equal to 0.002). Thus, ulcerative colitis
      patients appear to benefit from increased contact with or higher than usual
      levels of these critical energy substrates.

PMID- 1988262
TI  - D-xylose absorption test. Urine or blood?
AB  - The D-xylose absorption test has been used during the last four decades for
      evaluation of malabsorption in the small intestine. However, some disagreement
      still exists about the recommended method of performing this test: the 1-hr blood
      test, the 5-hr urine test, or both. We evaluated the test by performing 125
      combined blood and urine tests in 111 patients. Normal xylose absorption was
      recorded in both blood and urine in 71 tests (group A, 56.8%). Abnormal test
      results in both blood and urine were recorded in 29 patients (group B, 23.2%).
      Only one patient had a pathological blood value and normal xylose excretion in
      the urine. Twenty-four patients (group D, 19.2%) had normal 1-hr blood xylose
      (greater than 25 mg/100 ml) with abnormal 5-hr urine xylose (less than 4.5 g/5
      hr). Fat and/or bile salt malabsorption were documented in 21 patients (87.5%) of
      this group using stool fat analysis and the [14C]cholylglycine breath test. These
      data suggest that in adults the 5-hr urine collection more accurately reflects
      intestinal absorption in comparison with the 1-hr blood value.

PMID- 1988263
TI  - Gallstone dissolution with methyl tert-butyl ether in 120 patients--efficacy and
      safety.
AB  - Of 612 patients with cholesterol gallbladder stones, 120 were eligible for
      percutaneous transhepatic litholysis with methyl tert-butyl ether (MTBE).
      Puncture of the gallbladder was successful in 117/120 (97.5%). In 113/117 (96.6%)
      the stones dissolved. With solitary stones, treatment lasted for an average of 4
      hr, with multiple stones 10 hr. Mean hospitalization was 3.6 days. In 3/117
      (2.6%) patients a bile leakage developed; 33% reported mild complaints. After the
      end of treatment 34% had some residue in the gallbladder; two of these patients
      developed recurrent stones. MTBE is exhaled, is distributed in fatty tissue, and
      is excreted renally together with its metabolite tert-butanol. Methanol was found
      only in traces. Gallbladder histology of six patients showed chronic
      cholecystitis. Since these findings were independent of treatment time and the
      interval between treatment end and operation, they are most consistent with stone
      related changes rather than caused by MTBE.

PMID- 1988264
TI  - Medical dissolution of gallstones. Clinical experience of d-limonene as a simple,
      safe, and effective solvent.
AB  - Retained gallstones in the bile ducts account for 60-70% of all the cases of
      postcholecystectomy syndromes. A solvent d-limonene preparation was injected
      directly to the biliary system of 200 patients to dissolve or disintegrate the
      retained gallstones. The outcomes were: retained stones completely disappeared in
      96 cases (48%); partial dissolution in 29 (14.5%); chelating agent was also used
      with partial dissolution in 16 (8%); ineffective in 59 (24.5%). To make this
      method more effective, several guidelines should be observed including an in
      vitro trial dissolution test. Cautious observation for possible side effects and
      frequent hepatic and pancreatic function tests during the treatment with this
      preparation also should be performed.

PMID- 1988266
TI  - Treatment of pruritus of primary biliary cirrhosis with rifampin.
AB  - Pruritus can be a debilitating symptom in patients with chronic cholestasis.
      Based on previous reports of its efficacy, we evaluated the impact of rifampin on
      the pruritus associated with primary biliary cirrhosis. Fourteen patients were
      included in a randomized, crossover study. After a 15-day washout period,
      subjects were followed for three weeks. During the first and third week, patients
      received 600 mg of rifampin or placebo; no treatment was administered during the
      second week. Pruritus was subjectively scored on a scale from 0 to 100. With
      rifampin, pruritus disappeared in 11 patients and partially improved in three;
      with placebo, only two had a partial response (P less than 0.001). Six patients
      with a prior poor or no response to cholestyramine improved with rifampin. No
      changes in biochemical tests or side effects were observed during this period. We
      conclude that short-term administration of rifampin relieves pruritus in primary
      biliary cirrhosis. When administered over a period of eight months in an open
      study, the relief of pruritus was maintained, while one individual developed an
      allergic reaction. Rifampin appears to be a safe drug in the management of the
      pruritus of primary biliary cirrhosis.

PMID- 1988265
TI  - Evaluation of portal-systemic shunting in rats from mesenteric and splenic beds.
AB  - In rats with partial portal vein ligation, 95 +/- 0.9% of the splenic blood flow
      is shunted from the portal to the systemic circulation when an intrasplenic
      injection of microspheres is used to determine the degree of shunting. Despite
      this magnitude of portal-systemic shunting, several biochemical and endocrine
      consequences of portal-systemic shunting occur at levels below what is expected
      for the degree of shunting found. In an effort to resolve these discordant
      findings, shunting from both the splenic and the mesenteric bed was studied in
      anesthetized portal hypertensive rats with various degrees and/or duration of
      portal vein stenosis. The shunting from the mesenteric bed averaged 66.7 +/-
      29.9% (range 5.1-99.1%) and was influenced both by the degree and duration of
      portal vein stenosis. In contrast, shunting from the splenic bed averaged 97.3 +/
      4.0% (range 79-99.9%) and demonstrated no variation between groups determined by
      the degree of portal vein stenosis. The shunting from the splenic bed was
      consistently greater than that found from the mesenteric bed. Mesenteric but not
      splenic shunting correlated with serum bile acid levels. Mesenteric shunting was
      related inversely to the weight-adjusted liver mass and to serum testosterone
      levels. Based upon these data obtained in portal hypertensive rats, it is
      concluded that splenic injections of microspheres overestimate portal-systemic
      shunting. In contrast, mesenteric injections of microspheres yield values for
      shunting that correlate well with independently determined biochemical and
      endocrine consequences of shunting. These observations support the validity of
      the mesenteric shunting measurements obtained.

PMID- 1988267
TI  - Effect of chronic administration of cyclosporin A on hepatic uptake and biliary
      secretion of bromosulfophthalein in rat.
AB  - Cyclosporin A (CyA) decreases bile flow and bile salt secretion in the rat. The
      purpose of this study was to examine the influence of CyA on the hepatic
      transport of bromosulfophthalein (BSP). Male Sprague-Dawley rats were injected
      with CyA at the daily dose of 10 mg/kg (treated animals) or solvent (controls)
      during three weeks. Hepatic uptake of BSP (assessed by the plasma disappearance
      curve of the dye) and biliary secretion during infusions (95.5 and 178
      nmol/min/100 g) were examined in both groups. Administration of CyA resulted in a
      decrease in both bile flow and BSP biliary secretion at the two infusion rates
      used. BSP plasma disappearance rate was significantly lower in treated animals
      than in controls. Conjugation of the dye was unaffected by CyA. There was no
      modification in ALT activity or in liver histology. These data show that chronic
      administration of CyA in rats decreases both hepatic uptake and biliary secretion
      of BSP. Thus, the inhibitory effect of CyA on biliary secretion is not limited to
      bile salts but also is observed with other cholephilic substances.

PMID- 1988268
TI  - Achalasia in the elderly. Effects of aging on clinical presentation and outcome.
AB  - Clinical and manometric data from 13 elderly subjects with idiopathic achalasia
      (mean age 79 +/- 2 years) were compared with findings from younger subjects with
      the same disease (n = 79) to see if aging altered the presentation and outcome of
      this motor disorder. Fewer elderly subjects complained of chest pain (27% vs
      53%), and the pain was significantly less severe (P less than 0.01). Other
      presenting features (including sex, duration of symptoms, and presence and
      severity of dysphagia) did not differ between the groups. Across all patients,
      age weakly and inversely correlated with residual postdeglutitive lower
      esophageal sphincter; (LES) pressure (R = -0.34), and residual pressure was
      significantly lower in the older subjects (8.0 +/- 1.3 mm Hg vs. 11.9 +/- 0.8 mm
      Hg; P = 0.02). No differences in basal LES pressure or esophageal-body
      contraction amplitudes were present between the groups. Initial success with
      pneumatic dilation was similar in the two subject groups, but the number of older
      subjects available for analysis was too small to draw strong conclusions. These
      results indicate that aging decreases the elevation of LES residual pressure that
      occurs with achalasia. As elderly achalasia patients also present with less chest
      pain, the findings may be interrelated.

PMID- 1988270
TI  - Are we training consultants in gastroenterology?

PMID- 1988269
TI  - Prospective study on prevalence of esophageal chest pain in patients referred on
      an elective basis to a cardiac unit for suspected myocardial ischemia.
AB  - The prevalence of esophageal chest pain was studied prospectively in patients
      referred on an elective basis to a cardiac unit for suspected myocardial
      ischemia. A group of 248 consecutive patients without previously documented heart
      disease was admitted for elective diagnostic coronary angiography. The clinical
      history classified 185 patients as having anginal pain and the coronary angiogram
      was normal in 48 of them. In 37 of these 48 patients full esophageal testing was
      performed including 24-hr intraesophageal pH and pressure recordings with
      indication of chest pain episodes as well as a number of esophageal provocation
      tests, ie, acid perfusion, edrophonium stimulation, balloon distension, and
      ergonovine stimulation, all performed under continuous esophageal manometric and
      electrocardiographic monitoring. In 19 of these 37 patients, the familiar chest
      pain could be reproduced by esophageal provocative testing without ischemic ST-T
      segment alterations; six of these 19 patients had also a positive 24-hr pH and
      pressure recording. These data strongly suggest an esophageal origin of chest
      pain in half the patients with typical angina and a normal coronary angiogram.

PMID- 1988271
TI  - Ischemic colitis in a crack abuser.
AB  - We report a case of acute colitis temporally associated with smoking crack.
      Colonoscopy revealed a patchy left-sided hemorrhagic inflammation from the
      rectosigmoid colon to the splenic flexure. Biopsy specimens were consistent with
      resolving ischemic colitis. This entity should be considered in the differential
      diagnosis of acute bloody diarrhea in recreational drug users.

PMID- 1988273
TI  - [Organ-preserving surgery of renal cell carcinoma. The surgical technic, results
      and complications].
AB  - Operative method, course and complications were analysed retrospectively in 120
      patients in whom a kidney tumour had been resected without nephrectomy. In 49
      patients (18 women and 31 men, mean age 59 [38-77] years; 45 renal-cell
      carcinomas, 4 benign renal tumours) there was an "imperative indication" for an
      organ-preserving operation, because nephrectomy would have made dialysis
      obligatory. In 74 patients with a healthy contralateral kidney (25 women, 49 men,
      mean age 55 [31-74] years; 61 renal-cell carcinomas, 13 benign tumours) the
      tumour was enucleated by choice; 55 of these patients were symptom-free. 36 of 49
      patients with an imperative indication are without sign of tumour progression
      after a mean follow-up period of 4.5 years. In two there was a recurrence after 4
      and 5 years, respectively, requiring a second organ-preserving operation. Known
      metastases were present in 3 of 6 patients who died of their tumours. 68 of 74
      patients operated on electively are without signs of tumour progression after a
      mean follow-up period of 3.3 years. One patient died from tumour metastases. Two
      patients had tumour recurrence, requiring nephrectomy and enucleation,
      respectively.

PMID- 1988272
TI  - Pancreatic ascites presenting in infancy, with review of the literature.
AB  - We report a 4-month-old boy with massive ascites in whom a diagnosis of
      pancreatitis was made on a raised ascitic amylase level after two inconclusive
      laparotomies. He developed a pseudocyst which was managed with repeated
      percutaneous needle aspirations, nutrition being maintained intravenously.
      Endoscopic retrograde cholangiopancreatography (ERCP) demonstrated a congenital
      intra-pancreatic cyst. He thrived after operation drainage for recurrent
      pseudocyst, but repeat ERCP shows that the cyst in the head of the pancreas
      remains. Pancreatic ascites is rare in children and diagnosis is frequently
      delayed. A third of reported cases in childhood present in the first year of
      life. A search for the underlying cause should include an ERCP to demonstrate
      abnormalities of the pancreaticobiliary ducts.

PMID- 1988274
TI  - [Imaging procedures prior to the extracorporeal shockwave lithotripsy of
      gallstones].
AB  - In order to determine whether cholecystography and computed tomography (CT) are
      capable of better gallstone characterization than conventional radiography alone,
      91 patients (76 females, 15 males; mean age 47 +/- 12 years) with symptomatic
      single gallstones were studied prospectively prior to extracorporeal shock-wave
      lithotripsy with concomitant oral stone dissolution therapy. In addition, the
      value of oral cholecystography in demonstrating patency of the cystic duct was
      compared with ultrasound assessment of gallbladder function. Despite "negative"
      plain gallbladder radiographs in all patients, oral cholecystography showed
      significant stone calcification in 8 of the 91 patients and CT showed stone
      calcifications in 52 of the 91 patients. In 12 patients the maximum stone density
      was between 50 and 90 Hounsfield units, and in 40 patients it was more than 90
      Hounsfield units. CT revealed ring-like calcification in the majority (79%) of
      these stones. Oral cholecystography showed satisfactory concentration of contrast
      medium in all patients, while ultrasonography of the gallbladder following a
      chemically defined test meal demonstrated contractility of more than 50% of
      initial volume in 69 patients and of less than 30% in 9 patients. Although oral
      cholecystography is a simple, readily available complication-free method,
      ultrasound assessment of gallbladder contraction is better for selecting patients
      for extracorporeal shock-wave lithotripsy. CT allows significantly better
      characterization of gallstones than oral cholecystography and conventional plain
      gallbladder radiography.

PMID- 1988275
TI  - [Left bundle-branch block and primary benign heart tumor].
AB  - The electrocardiogram (ECG) of a 56-year-old woman suffering from insomnia and
      nervousness revealed left bundle branch block, an ECG two years previously having
      been normal. Echocardiography showed a perimyocardial space-occupying lesion in
      the area of the left ventricle. Magnetic resonance imaging demonstrated a 6 x 6 x
      7 cm solid tumour, which could not be separated from the myocardium of the dorsal
      portion of the ventricle and the left atrial wall. Coronary angiography
      demonstrated a few small atypical vessels originating from the right coronary
      artery. An endomyocardial biopsy was equivocal. An exploratory thoracotomy
      revealed a large, livid tumour which could not be resected because it involved a
      large area of the left ventricle and left atrium. Surgical biopsy showed a
      cavernous haemangioma. The subsequent course (ten months' follow-up) has so far
      been unremarkable.

PMID- 1988277
TI  - [The therapy of myasthenia gravis pseudoparalytica].

PMID- 1988276
TI  - [Extremity-threatening ischemia in ergotism. Successful treatment with the intra
      arterial administration of nifedipine].
AB  - A 39-year-old woman suffering from migraine took two suppositories of an
      ergotamine-containing proprietary drug (Cafergot, containing 2 mg ergotamine
      tartrate) for the first time again after an abstinence of two years. Twenty-four
      hours later she developed symptoms of decreased peripheral blood flow in all four
      limbs. Walking distance without pain was reduced to 100 m, but the severest
      changes affected the right arm, with livid discolorations and complete immobility
      16 hours after the onset of symptoms. Despite administration of morphine
      derivatives the pain progressively increased. Angiography demonstrated spastic
      narrowing of all arm arteries below the axillary artery. No vessels were
      visualized below the lower-arm bifurcation. Thereupon 4 mg nifedipine were
      injected through the angio-catheter within 30 min (five individual doses of 0.8
      mg each). This was followed by intravenous infusion of 0.5 mg/h. The pain
      immediately decreased and the livid discoloration as well as impaired arm
      movement improved. A residual deficit, incomplete lesion of the median nerve,
      persisted but gradually regressed during the following two months.

PMID- 1988278
TI  - [The carotid pressure test].

PMID- 1988279
TI  - [A visual disorder as the initial symptom of hairy cell leukemia].

PMID- 1988280
TI  - [The elevated thyroxin requirement of pregnant women with primary
      hypothyroidism].

PMID- 1988281
TI  - Chromosome topology in mammalian interphase nuclei.
AB  - Since 1968, when Comings published the pioneering paper on "the rationale for an
      ordered arrangement of chromatin in the interphase nucleus," technical methods
      have progressed tremendously and improved our understanding of interphase
      organization. The existence of highly ordered organizational patterns of the cell
      nucleus appears to be beyond any doubt and it is difficult to escape the
      conclusion that interphase chromosome topology is important for the complex
      regulation of the many varied and interrelated nuclear processes. However, it is
      worth emphasizing that a universally valid principle of chromosome arrangement
      does not exist and, therefore, any generalization of interphase patterns can be
      misleading. The factors of order according to which the chromosomes are arranged
      inside the nucleus are manifold: (1) Individual chromosomes remain in spatially
      separated domains throughout interphase, preventing an intermingling of the
      decondensed euchromatin. (2) Chromosome regions that contain constitutive
      heterochromatin associate into larger chromocenters. (3) In most cell types
      direct associations between interphase domains of homologous chromosomes are not
      observed. In others homologous heterochromatic regions tend to be paired
      preferentially. (4) Interphase chromosomes do not float freely in the
      nucleoplasm; they are associated to varying degrees with the nuclear membrane and
      other components of the nuclear scaffold. The number of attachment sites for each
      chromosome to the nuclear membrane is relatively low. (5) The positions of
      centromeres (and pericentromeric heterochromatin) are nonrandom and
      characteristic of each cell type. Specific centromere movements occur during the
      cell cycle, during differentiation, and under certain pathophysiological
      conditions. (6) The telomeric chromosome ends are particularly prone to associate
      in certain somatic cell types and in meiotic prophase cells. (7) The arrangement
      of repetitive DNA families appears to determine a structural framework of the
      interphase nucleus. Different cell types of one organism can exhibit marked
      differences in their repetitive DNA framework, whereas cells that are in an
      identical differentiated state or an identical phase of the cell cycle often show
      comparable interphase patterns even in evolutionarily distant species. (8) The
      various steps of ribosome biogenesis take place in a precise fashion within a
      separate nuclear domain, the nucleolus. The topologically well-defined nucleolar
      substructures are required for rDNA transcription and pre-rRNA processing. (9) A
      compartmentalization of transcriptional and processing events is also evident in
      the rest of the nucleus. However, it is not yet known if the in situ sites of
      transcription and RNA processing for a particular (nonribosomal) gene or gene
      family are actually adjacent. (10) DNA replication is precisely spatiotemporally
      regulated within the nucleus. The replication domains are immobilized on the
      nuclear matrix.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1988282
TI  - Effects of oxygen free radicals on articular chondrocytes in culture: c-myc and c
      Ha-ras messenger RNAs and proliferation kinetics.
AB  - Since oxygen free radicals are believed to play an important role in cartilage
      degradation, we studied the effects of these radicals generated by the
      hypoxanthine xanthine oxidase system on rabbit articular chondrocytes in culture.
      Among the damages induced by these radicals, cell proliferation inhibition and G2
      arrest were observed. To elucidate the mechanisms involved in this phenomenon,
      the expression of c-myc and c-Ha-ras genes whose products are associated with
      cell growth control was studied. Results showed that in chondrocytes, c-myc and c
      Ha-ras expression was particularly important during the G1 phase of the cell
      cycle and that oxygen reactive species, especially H2O2, induced an important
      decrease of c-myc and c-Ha-ras mRNA levels. Chondrocytes cell cycle analysis
      revealed an accumulation of cells in G2 phase. It led us to suggest that the
      chondrocyte cell cycle perturbations observed after oxygen free radicals
      treatment could be associated with the decrease of c-myc and c-Ha-ras expression.

PMID- 1988283
TI  - Osteogenin promotes reexpression of cartilage phenotype by dedifferentiated
      articular chondrocytes in serum-free medium.
AB  - Chondrocytes lose their phenotypic traits, including type II collagen, after
      serial passage in monolayer cultures. Osteogenin, a bone morphogenetic protein,
      induces cartilage and bone in nonskeletal sites. This investigation examined the
      ability of osteogenin to promote the reexpression of cartilage phenotype by
      dedifferentiated chondrocytes obtained from rabbit articular cartilage. The
      results revealed that osteogenin, in synergism with selected growth factors,
      promoted the reexpression of type II collagen and proteoglycans by
      dedifferentiated chondrocytes in agarose. Insulin, a constituent of the basal
      medium, appeared to be essential for the colony-forming aspect of this
      phenomenon, since when insulin was replaced by insulin-like growth factor-1
      colony formation did not occur. Epidermal growth factor, platelet-derived growth
      factor (PDGF), and basic fibroblast growth factor appeared to be an optimal
      combination for the action of osteogenin. Neutralizing antibodies to transforming
      growth factor-beta did not influence the response to osteogenin. It is noteworthy
      that, compared to freshly passaged cells, those stored in liquid nitrogen were
      not as responsive to osteogenin and growth factors. A higher concentration of
      fibroblast growth factor in conjunction with osteogenin and PDGF, increased the
      responsiveness of frozen cells only in part, as the Alcian blue-positive
      proteoglycan matrix was not restored completely.

PMID- 1988284
TI  - Modulation of endothelial cell surface glycoconjugate expression by organ-derived
      biomatrices.
AB  - Cell surface molecules play an important role in cellular communication,
      migration, and adherence. Here, we show the effect of organ-derived biomatrices
      on endothelial cell surface glycosylation. Five different lectins (with and
      without neuraminidase treatment) have been used as probes in an enzyme-linked
      lectin assay to quantitatively detect glycoconjugates on endothelial cells (BAEC)
      grown on tissue culture plastic or biomatrices isolated from bovine lung, liver,
      and kidney. BAEC generally exhibit strong binding of concanavalin A (Con A),
      Ricinus communis agglutinin I (RCA-I), wheat germ agglutinin (WGA), and soybean
      agglutinin, and peanut agglutinin after neuraminidase pretreatment of cells (Neu
      SBA and Neu-PNA), while SBA and PNA consistently bind weakly to BAEC. BAEC grown
      on organ-derived biomatrices exhibit significantly altered binding intensities of
      Con A, RCA-I, WGA, and Neu-PNA: BAEC cultured on lung- or kidney-derived
      biomatrices express significantly stronger binding affinities for Con A and RCA-I
      than BAEC grown on liver-derived biomatrix or tissue culture plastic. In
      contrast, BAEC binding of WGA and PNA (after treatment of cells with
      neuraminidase) is significantly reduced when BAEC are grown on liver- or kidney
      derived biomatrix. Quantitative lectin immunogold electron microscopy reveals
      consistently stronger lectin binding over nuclear regions compared to junctional
      regions between neighboring cells. These results indicate that extracellular
      matrix components regulate endothelial cell surface glycoconjugate expression,
      which determines cellular functions, e.g., preferential adhesion of lymphocytes
      or metastatic tumor cells.

PMID- 1988285
TI  - Retinoids enhance lectin binding to gp130, a glycoprotein of NIH-3T3 cells:
      correlation with cell growth and adhesion.
AB  - Our previous work has shown that retinoic acid (RA) enhances fibroblast cell
      attachment to plastic and to laminin. The treatment of NIH-3T3 cells with RA for
      2 days also caused a reproducible increase in the binding of the lectin Phaseolus
      vulgaris leukoagglutinin (PHA-L) to a glycoprotein of molecular weight 130,000
      (gp130) as judged by SDS-PAGE analysis. This finding is consistent with an
      increased number of beta-1,6-linked N-acetylglucosaminyl residues on gp130. Of
      the 11 additional lectins tested Ricinus communis agglutinin I (RCA), Phaseolus
      vulgaris erythroagglutinin (PHA-E), soybean agglutinin (SBA), and succinylated
      wheat germ agglutinin (sWGA) showed a significant increase in binding
      specifically to gp130. Similar to RA, 13-cis-RA and 3,5-di-tert-butyl-4-chalcone
      carboxylic acid, a synthetic retinoid, also increased PHA-L binding to gp130;
      they also enhanced cell adhesiveness and inhibited cell growth. N-(4
      Hydroxyphenyl)-all-trans-retinamide and thyroxine failed to influence adhesion
      and did not increase PHA-L binding to gp130. Moreover these compounds also failed
      to inhibit cell growth and to alter the morphology of the cultured cells. Since
      trypsin is utilized to remove cells from the culture dishes before they are used
      in the attachment assay to laminin, we studied the effect of this trypsinization
      step on PHA-L binding to gp130. Trypsin reduced PHA-L binding thus suggesting
      cell surface localization of gp130. After trypsin treatment RA-treated cells
      still showed enhanced PHA-L binding compared to dimethyl sulfoxide (DMSO)
      control. In conclusion RA-induced cell adhesiveness and growth inhibition are
      accompanied by an increase in the PHA-L, PHA-E, SBA, RCA, and sWGA binding to
      gp130. The sensitivity of gp130 to trypsin suggests that it is a cell surface
      glycoprotein.

PMID- 1988286
TI  - Immunoelectron microscopic localization of estrogen receptor on pre-mRNA
      containing constituents of rat uterine cell nuclei.
AB  - The localization and quantitative changes of estradiol receptor (ER) were studied
      by means of immunogold-electron microscope methods using a polyclonal antibody
      directed against an amino acid sequence representing the DNA binding site of ER,
      a monoclonal antibody against hnRNP core protein, and anti-DNA antibody. The
      uteri of normal rats in estrus and those of ovariectomized females were used.
      Ovariectomized rats were studied 21 days after surgery at different times after
      the injection of normal saline or estradiol-17 beta. The density of labeling was
      measured in interchromatin space, compact chromatin, nucleolus, cytoplasm, and
      background of epithelial cells, muscle cells, and fibroblasts. In the three types
      of cells ER was found mainly on extranucleolar ribonucleoprotein (RNP) fibrils.
      In epithelial and muscle cells the nucleolus was labeled but compact chromatin
      was not labeled. In epithelial cells there was a low but significant labeling of
      the cytoplasm. Fibroblasts exhibited a low labeling of the compact chromatin.
      Ovariectomy did not change these distributions. The estradiol injection increased
      labeling in all compartments of epithelial and muscle cells but decreased the
      labeling of compact chromatin of fibroblasts. These results show: (a) that ER is
      mainly nuclear but it is also present in the cytoplasm, (b) that ER binds to the
      nuclear particles containing newly synthesized RNA, and (c) that the binding to
      RNPs does not block the DNA binding domain of the ER.

PMID- 1988287
TI  - The relationship between the rate of entry into S phase, concentration of DNA
      polymerase alpha, and cell volume in human diploid fibroblast-like monokaryon
      cells.
AB  - We have examined the kinetic relationship between the rate of entry into the S
      phase in human diploid fibroblast-like (HDFL) monokaryon cells and (1) the
      concentration of DNA polymerase alpha activity and (2) the cell volume. In the
      former studies, a first-order dependence between the rate of entry into the S
      phase and the concentration of DNA polymerase alpha activity was observed,
      consistent with the enzyme, or a coregulated factor, being rate limiting for this
      metabolic process. Examination of the nature of the dependence of the rate of
      entry into the S phase upon cell volume revealed a more complex relationship. The
      results obtained in studies with synchronized cultures are consistent with the
      presence of two to three rate-limiting reactants when cell volume is the
      independent variable. Studies with asynchronous HDFL cell cultures revealed that
      the smallest cells in the G1 population, presumably the early G1 cells, enter the
      S phase at an increasing rate as a function of cell volume up to a certain size,
      beyond which the cells enter at a decreasing rate similar to that observed in the
      studies with the synchronized cultures. Similar studies examining the
      relationship between cell volume and the rate of entry into S phase in three
      established immortal cell lines revealed positive correlation between the rate of
      entry into S phase and cell volume throughout the size range of the G1
      population. This latter observation suggests that the factors involved in the
      initiation of the S phase may be present in concentrations that are not rate
      limiting in immortal cell lines.

PMID- 1988289
TI  - Timing of oral morphogenesis and its relation to commitment to division in
      Paramecium tetraurelia.
AB  - The interval between commitment to division and fission in synchronous cell
      samples is a constant fraction of the cell cycle (0.2) in cell cycles up to 6.5 h
      in duration. In longer cell cycles this interval has a fixed duration of about 80
      min. The point of commitment to division is associated with the six-rowed analage
      stage of oral primordium development (stage V). At this stage cells carrying the
      cc1 mutation are not blocked by transfer to restrictive conditions but rather
      proceed to division. Stage V is also the stabilization point for oral anlagen.
      When shifted to restrictive conditions prior to this stage, development is
      arrested and resorption of analgen is initiated. The cc1 mutation also blocks
      contractile vacuole duplication and migration under restrictive conditions. The
      cc1 gene function is required continuously prior to the transition point. The
      timing of morphogenetic stages in asynchronous cells is roughly similar to that
      in synchronous cells. There are, however, significant differences in timing as
      estimated by the two experimental procedures.

PMID- 1988288
TI  - DNA polymerase alpha and the regulation of entry into S phase in heterokaryons.
AB  - We have previously reported that the DNA polymerase alpha activity/unit cellular
      protein is decreased in late-passage (senescent) human diploid fibroblast-like
      (HDFL) cultures due to the cellular enlargement associated with in vitro aging.
      In the studies described here, we have used cell fusion technology to investigate
      the formal kinetic relationship between the concentration of DNA polymerase alpha
      and the rate of reinitiation of DNA synthesis in nuclei from senescent cells.
      Heterokaryons were derived from the fusion of senescent cells to a series of
      actively dividing cell types with inherently different DNA polymerase alpha
      activities per cell. A kinetic analysis revealed a first-order relationship
      between the entry into S phase of senescent nuclei and the concentration of DNA
      polymerase alpha activity calculated to be in heterokaryons. This result suggests
      that increases in cell volume may be related to the decline in proliferative
      activity of late-passage HDFL cells, via "dilution" of factors essential for
      cellular replication.

PMID- 1988290
TI  - Nuclear localization of endogenous basic fibroblast growth factor in cultured
      endothelial cells.
AB  - Indirect immunofluorescence using anti-human placental bFGF antibodies
      demonstrates the presence of bFGF-like reactivity in the cytoplasm and in the
      nucleus of adult bovine aortic endothelial cells and of normal and transformed
      fetal bovine aortic endothelial AG 7680 and GM 7372 cells. Biologically active
      immunoreactive Mr 18,000 bFGF can be isolated by heparin-Sepharose affinity
      chromatography from the extract of GM 7372 cell nuclei. Quantitation of bFGF
      content by biological and immunological methods indicates that 100,000 bFGF
      molecules per nucleus are present in GM 7372 cells, with nuclear bFGF
      corresponding to 25-30% of total cellular bFGF. Immunoprecipitation experiments
      demonstrate that the nuclear localization of newly synthesized bFGF occurs when
      GM 7372 cells are biosynthetically labeled both in the absence and in the
      presence of suramin, a molecule that inhibits the binding of bFGF to its plasma
      membrane receptor. Thus the data indicate that endogenous bFGF undergoes an
      intracellular sorting to the nucleus of the endothelial cell.

PMID- 1988291
TI  - Contact formation and transfer of mannose BSA gold from macrophages to cocultured
      fibroblasts.
AB  - When macrophages were cocultured with fibroblasts many of the cells formed firm
      contacts. In some of these contacts both cell types were closely apposed and in
      others they were more clearly separated with numerous pseudopodia extending from
      macrophages toward the fibroblasts. Many small vesicles similar in structure to
      caveoli were observed immediately beneath the plasma membrane of some fibroblasts
      in regions immediately adjacent to areas of contact with macrophages. The
      membrane integrity of both cell types was always maintained and no connecting
      cytoplasmic strands were observed between contacting cells. Junctions were freely
      permeable to ruthenium red and less permeable to the larger cationized ferritin.
      Gold conjugated to mannose BSA was taken up readily by macrophages but not by
      fibroblasts. When fibroblasts were cocultured with macrophages that had been
      labeled with endocytosed gold, increasing amounts were transferred to them. Gold
      was observed within gaps formed between cocultured cells and within recipient
      fibroblasts in vesicles anatomically similar to lysosomes. These points of
      contact thus appear to provide a series of specialized protected clefts into
      which directed exocytosis of ligands from donor cells can take place and from
      which endocytosis into recipient cells is facilitated.

PMID- 1988292
TI  - Organization of intestinal epithelial cells into multicellular structures
      requires laminin and functional actin microfilaments.
AB  - Epithelial cell organization into multicellular structures is a critical
      biological process required for both organogenesis and repair following injury.
      The basement membrane and the cytoskeleton have important roles in this process;
      however, the functions of individual components of basement membrane and
      cytoskeleton are poorly understood. We used IEC-6 cells, a rat intestinal crypt
      cell line, grown on a three-dimensional gel of reconstituted basement membrane as
      a model system to determine which extracellular matrix and cytoskeletal
      components mediate intestinal epithelial cell organization. The cells entered the
      gel and formed hollow, tubular structures that resembled intestinal crypts. These
      structures were characterized by a single layer of polarized cells with apical
      tight junctions and microvilli on the luminal surface. Antiserum to laminin and
      the pentapeptide Tyr-Ile-Gly-Ser-Arg (which prevents cell attachment to laminin)
      inhibited this organization, but a control pentapeptide (Tyr-Tyr-Gly-Asp-Ala) and
      antiserum to collagen IV did not. Cytochalasin B, which interferes with actin
      microfilament polymerization, also inhibited organization of cells into
      multicellular structures, but vinblastine and Colcemid, which disrupt
      microtubules, and cycloheximide, which inhibits protein synthesis, did not. We
      conclude that organization of intestinal epithelial cells on a basement membrane
      into multicellular structures results from specific interactions between cells
      and laminin and requires intact actin microfilaments.

PMID- 1988293
TI  - Expression of nuclear matrix proteins in rat liver tissue.
AB  - We have studied the synthesis of nuclear matrix proteins as it occurs in the rat
      liver. To investigate their kinetics in tissue, nuclear matrix proteins were
      prepared from liver of rats injected with radioactive methionine. Synthesis of
      lamins was not observed in quiescent hepatocytes although they were the principal
      proteins of this subcellular fraction, suggesting that lamins are very stable in
      the liver. When hepatocytes were stimulated to divide by partial hepatectomy,
      only synthesis of lamin B was initiated. Many proteins not visible on Coomassie
      blue-stained gels were detectable by autoradiography. In the nuclear matrix
      extracts of quiescent hepatocytes, one of the most prominently labeled ones was a
      protein of 70 kDa. After hepatectomy, an additional protein of 62 kDa was
      detectable. These proteins were visible 1 h after the injection of radioactivity,
      but were no longer observed in nuclear matrices prepared 24 h after injection.
      These experiments indicate that in addition to lamins, two nuclear matrix
      proteins are present in the rat liver that were not detected previously, perhaps
      because of their rapid turnover.

PMID- 1988294
TI  - The effects of microinjection of rhodamine-phalloidin on mitosis and cytokinesis
      in early stage Drosophila embryos.
AB  - Rhodamine-phalloidin was microinjected into early stage Drosophila embryos, which
      were then allowed to develop for various times, fixed, and examined by
      fluorescence microscopy. A gradient of effects was seen. Close to the site of
      injection an area of diffuse bright fluorescence was found which included lumps
      and long strands of fluorescent material. Around this region particular
      cytoplasmic domains showed a denser F-actin distribution. These domains included
      the nuclear islands of the preblastoderm, the cortical caps of the syncytial
      blastoderm, and the contractile ring network which forms during cellularization
      of the blastoderm. It is proposed that these domains are regions of preferential
      actin polymerization under the appropriate cellular conditions and that the
      injected phalloidin causes incorporation of additional polymer into existing
      structures. Further away the pattern of phalloidin staining corresponded to that
      found with fixed material. In contrast to the domains of apparent additional F
      actin polymerization a reduction of actin incorporated into small aggregates was
      found, both in syncytial blastoderm stages and during cellularization. This
      occurred in regions where additional actin had been incorporated into adjacent
      actin-rich structures. A storage role for the aggregates, which are depleted when
      F-actin is polymerized, is proposed. Both mitosis and cytokinesis were found to
      be slowed but the inhibition was only transient. However, most embryos died
      without differentiating. Rarely, differentiated tissues formed and the
      musculature was strongly stained by rh-phalloidin. When embryos were injected
      immediately prior to the start of cellularization cytokinesis was inhibited only
      locally and continued normally elsewhere. This finding argues against the
      hypothesis that contraction of an actomyosin network over the whole surface is
      the only force involved in the cellularization of the blastoderm and that local
      factors, e.g., plasmalemma extension, must be involved.

PMID- 1988295
TI  - Uncoupling of the calcium-sensing mechanism and differentiation in squamous
      carcinoma cell lines.
AB  - Increases in the intracellular calcium (Cai) levels, induced either by
      extracellular calcium or by calcium ionophores, stimulate the terminal
      differentiation of normal human keratinocytes in culture (NHK). Despite extensive
      differences in phenotypic expression, squamous carcinoma cell lines (SCC lines)
      display only partial terminal differentiation even in the presence of normal
      extracellular calcium. Therefore, in this study, we evaluated whether the
      inability of SCC lines to differentiate normally is due to a defect in achieving
      adequate levels of Cai. Membrane-bound transglutaminase activity and involucrin
      levels of the various SCC lines were lower than those of NHK and correlated with
      their low extent of cornified envelope formation. Ionomycin, a calcium ionophore,
      acutely increased cornified envelope formation of NHK 60- to 70-fold, but only
      initiated a 1- to 5-fold increase in SCC lines. Yet resting Cai levels in and the
      Cai response to various agents of SCC lines were similar or higher than those of
      NHK. Extracellular calcium evoked a rapid, transient and a slower, sustained
      increase of Cai. Extracellular ATP increased Cai by a rapid release from
      intracellular sources. Ionomycin, on the other hand, increased Cai from both
      intracellular compartments and extracellular sources. Thus, these studies
      indicate that the abnormalities in differentiation among SCC lines do not appear
      to involve their calcium-sensing mechanism. An uncoupling of the Cai changes to
      the synthesis of the precursor molecules required for differentiation may be
      responsible for the defect in differentiation displayed by these SCC lines.

PMID- 1988296
TI  - Differential regulation of HSC70, HSP70, HSP90 alpha, and HSP90 beta mRNA
      expression by mitogen activation and heat shock in human lymphocytes.
AB  - A subset of heat shock proteins, HSP90 alpha, HSP90 beta, and a member of the
      HSP70 family, HSC70, shows enhanced synthesis following mitogenic activation as
      well as heat shock in human peripheral blood mononuclear cells. In this study, we
      have examined expression of mRNA for these proteins, including the major 70-kDa
      heat shock protein, HSP70, in mononuclear cells following either heat shock or
      mitogenic activation with phytohemagglutinin (PHA), ionomycin, and the phorbol
      ester, tetradecanoyl phorbol acetate. The results demonstrate that the kinetics
      of mRNA expression of these four genes generally parallel the kinetics of
      enhanced protein synthesis seen following either heat shock or mitogen activation
      and provide clear evidence that mitogen-induced synthesis of HSC70 and HSP90 is
      due to increased mRNA levels and not simply to enhanced translation of
      preexisting mRNA. Although most previous studies have focused on cell cycle
      regulation of HSP70 mRNA, we found that HSP70 mRNA was only slightly and
      transiently induced by PHA activation, while HSC70 is the predominant 70-kDa heat
      shock protein homologue induced by mitogens. Similarly, HSP90 alpha appears more
      inducible by heat shock than mitogens while the opposite is true for HSP90 beta.
      These results suggest that, although HSP70 and HSC70 have been shown to contain
      similar promoter regions, additional regulatory mechanisms which result in
      differential expression to a given stimulus must exist. They clearly demonstrate
      that human lymphocytes are an important model system for determining mechanisms
      for regulation of heat shock protein synthesis in unstressed cells. Finally,
      based on kinetics of mRNA expression, the results are consistent with the
      hypothesis that HSC70 and HSP90 gene expression are driven by an IL-2/IL-2
      receptor-dependent pathway in human T cells.

PMID- 1988297
TI  - Isolation and characterization of hemidesmosomes from bovine corneal epithelial
      cells.
AB  - The hemidesmosome (HD) is a specialized cell-to-substratum junction of stratified
      and complex epithelia which is characterized by a cytoplasmic plaque to which
      intermediate filaments (IFs) are anchored. To identify and characterize HD
      constituents systematically, we have developed a procedure to isolate and
      fractionate HDs. When bovine corneal epithelium is peeled off from the
      extracellular matrix stroma, HDs attached to the basal lamina are left behind,
      together with tufts of cytokeratin IFs attached to the cytoplasmic HD plaques.
      After rinsing these residual basal cell elements with EDTA, the HDs could be
      mechanically detached from the stroma and collected by centrifugation. The
      fraction obtained was examined biochemically and electron microscopically,
      showing enrichment of HD structures as well as of a prominent 230-kDa
      polypeptide, the "pemphigoid antigen" known to be located in the HD plaque. In
      addition, the HD fraction revealed, besides residual amounts of corneal
      cytokeratins, major polypeptides of Mr 120, 180, 200, 230, and 480 kDa, of which
      the first three appeared to be glycoproteins. Using the isolated HDs for
      immunization, we prepared monoclonal antibodies specific for the 230- and 180-kDa
      polypeptides, respectively, and showed that both were exclusively located in HDs.
      This method for isolating HDs and the availability of antibodies to HD proteins
      will be useful in studies of the molecular organization of HDs and make HD
      research independent from human autoimmune antibodies.

PMID- 1988298
TI  - Nature of the Zn2+ requirement for DNA synthesis by 3T3 cells.
AB  - Transit of 3T3 cells from quiescence to S phase requires an adequate supply of
      Zn2+ during the second half of the transition. The nature of this requirement has
      been investigated. Completion of the Zn2(+)-dependent process required ongoing
      mRNA and protein synthesis but could be accomplished in serum-free medium.
      Combination of low Zn2+ availability with inhibition of mRNA synthesis by 5,6
      dichlororibofuranosylbenzimidazole or of protein synthesis by cycloheximide
      resulted in the cells almost completely reverting to a quiescent state. The
      results suggest that Zn2+ is required for the accumulation and maintenance of a
      protein involved in the progression of untransformed cells into S phase.

PMID- 1988299
TI  - Stimulation by xanthine oxidase of 3T3 Swiss fibroblasts and human lymphocytes.
AB  - Xanthine oxidase stimulates [3H]thymidine incorporation by 3T3 cells even in the
      absence of any added xanthine, but in the presence of, and synergistically with,
      insulin or various other growth-stimulating factors. Optimal stimulation was
      obtained with 2-3 mU enzyme/ml and higher concentrations were toxic. Xanthine
      oxidase also stimulated human peripheral blood lymphocytes in the presence of
      phytohemagglutinin and xanthine.

PMID- 1988300
TI  - Two classes of single-stranded regions evident in deproteinized preparations of
      replicating DNA isolated from mammalian cells.
AB  - In DNA isolated from proliferating human lymphoblastoid CCRF-CEM cells which had
      been pulse-labeled by exposure to [3H]thymidine for periods from 30 s to 10 min,
      single-stranded regions were analyzed by caffeine-gradient elution from
      benzoylated DEAE-cellulose. Two classes of structural defect were evident. Some
      replicating DNA exhibited single-stranded regions of approximately 200
      nucleotides, while most newly incorporated radioactivity was associated with DNA
      containing single-stranded regions from 900 to approximately 4000 nucleotides.
      The distribution of thymidine-derived radioactivity did not suggest sequential or
      preferential labeling of these DNA fractions as the incorporation time was
      varied. The findings may be correlated with recent proposals regarding the
      structural basis of eukaryotic DNA replication.

PMID- 1988301
TI  - A new method for quantifying keratinocyte differentiation using immunofluorescent
      staining of involucrin and cytofluorography.
AB  - Involucrin is a precursor protein of detergent-insoluble cornified envelope and a
      marker of terminal differentiation of epidermal keratinocytes. To quantify
      differentiation of cultured human keratinocytes, the population of involucrin
      positive cells was estimated by immunofluorescent staining using anti-involucrin
      antibody and flow cytometry. Normal human keratinocytes were cultured under three
      conditions for induction of differentiation: low Ca2+ concentration (0.1 mM
      Ca2+), high Ca2+ concentration (1.8 mM Ca2+), and high Ca2+ concentration with
      10% fetal bovine serum (FBS). The relationship between fluorescence intensity and
      involucrin synthesis was confirmed by visual examination of sorted cells. The
      population of involucrin-positive cells increased from 7.2 to 18.1% by elevating
      Ca2+ concentration and to 37.0% by adding FBS. The extent of cornified envelope
      formation under the same culture conditions was consistent with the estimation of
      involucrin-positive cells. The cytofluorographic analysis of involucrin synthesis
      made it possible to determine the number of differentiated cells in a large
      number of samples precisely and reliably. Thus, it is a useful method for
      quantifying keratinocyte differentiation.

PMID- 1988302
TI  - The effect of interleukin-1 on iron metabolism in rats.
AB  - The effect of interleukin-1 on iron metabolism in rats was evaluated. Plasma iron
      decreased from 184 +/- 16 micrograms/dl (mean +/- SE) to 24 +/- 12 at 6 hours
      after interleukin-1 intramuscular administration in non-fasting rats and 109 +/-
      6 micrograms/dl to 12 +/- 1 micrograms/dl in fasting rats, which was
      significantly lower than in control rats. Ferrokinetic studies showed a more
      rapid disappearance rate and lower iron turnover in interleukin-1-injected rats.
      The release of iron from the mononuclear phagocyte system to plasma was studied
      at 3 h after interleukin-1 administration. Although the percent of radioactivity
      in plasma of the total injected dose was 3.2 +/- 0.6% in interleukin-1, which was
      significantly lower than in the control rats (5.4 +/- 0.6%) at 9 h after
      intravenous injection of 59Fe chondroitin ferrous sulfate, there was no
      difference between the amount of 59Fe released from the mononuclear phagocyte
      system over the first 9 h in interleukin-1 and control rats. These data appear to
      imply that iron release is unimpaired but that, for some reason, there is an
      enhanced rate of clearance of the 59Fe once it has been released from the
      mononuclear phagocyte system into the plasma.

PMID- 1988303
TI  - Treatment of advanced myelodysplastic syndromes with recombinant interferon-alpha
      2b.
AB  - We examined the efficacy and toxicity of recombinant interferon-alpha 2b (rIFN
      alpha 2b) in 10 previously untreated patients with advanced myelodysplastic
      syndromes. Morphological subtypes were refractory anaemia with excess of blasts
      (RAEB) in 4, RAEB in transformation (RAEB/T) in 3 and chronic myelomonocytic
      leukaemia (CMML) in 3 cases. IFN was administered subcutaneously at increasing
      doses of 1 to 3 x 10(6) IU per day. The median duration of therapy was 6 months
      (range, 3 to 14). 2 patients, both with a diagnosis of CMML, achieved a complete
      and partial remission, respectively. In the complete responder, remission could
      be maintained for 9.5 months by daily administration of 1 x 10(6) IU IFN. The
      other patients were classified as failures, although in 4 cases a decrease of
      bone marrow blasts was noted and none of the patients progressed to overt
      leukaemia while being treated with IFN. During the study, all patients with RAEB
      and RAEB/T showed a moderate to severe reduction in peripheral leukocyte and
      platelet counts, requiring premature termination of IFN therapy in 5 cases.
      Despite adequate supportive measures, 2 patients died of pneumococcal pneumonia
      and gastrointestinal bleeding, respectively. In 1 patient, IFN therapy had to be
      stopped because of neurologic toxicity (polyneuropathy). From these data we
      conclude that rIFN-alpha 2b at the doses and schedule tried is not a useful
      treatment for advanced myelodysplastic syndromes. Patients with CMML, however,
      may be an exception and should further be considered as candidates for
      therapeutic trials with rIFN-alpha 2b.

PMID- 1988304
TI  - Mitoxantrone, etoposide, cytarabine and prednisone as salvage therapy for
      refractory non-Hodgkin lymphoma (NHL) and alternated with CHOP in previously
      untreated patients with NHL.
AB  - The treatment of relapsing or refractory high-grade malignant non-Hodgkin
      lymphoma (NHL) following CHOP chemotherapy remains a challenge for the clinician.
      In this study, 29 patients with relapsing or refractory high- or refractory low
      grade malignant NHL received a combination of mitoxantrone 12 mg/m2 i.v. on days
      1-2, cytarabine 100 mg/m2 i.v., b.d. d 1-2, etoposide 100 mg/m2 i.v. d 1-3 and
      prednisone 100 mg/m2 orally d 1-3 (ENAP). An overall response rate of 55%
      encouraged us to use ENAP alternated with conventional CHOP chemotherapy in 45
      previously untreated NHL patients (35 with high-grade and 10 with "aggressive"
      low-grade malignant NHL). All patients responded with a complete remission rate
      (CR) of (27%) and a partial remission rate (PR) of 73% after only one course of
      ENAP. After a median number of 3.5 ENAP/CHOP courses, the CR and PR rate was 69
      and 22%, respectively. Myelosuppression was pronounced and fever of unidentified
      origin and documented infections followed 59% of all cases given ENAP courses. In
      the last 19 previously untreated patients mitoxantrone was given at a dose of 10
      mg/m2 on d 1 and cytarabine 100 mg i.v., b.d. during d 1-2. Nonhematologic
      toxicity was mild. We conclude that this novel chemotherapy program is effective
      both as first-line and salvage treatment in patients with high-grade malignant
      NHL. Furthermore, ENAP appears clinically to be partly non-cross resistant with
      CHOP chemotherapy. The dose-limiting toxicity is myelosuppression. The
      combination should be explored as primary therapy in combination with other
      chemotherapy or radiotherapy programs.

PMID- 1988305
TI  - Clinical features and response to treatment of infradiaphragmatic Hodgkin's
      disease.
AB  - Among 247 patients with Hodgkin's disease, initial disease presentation was
      restricted to infradiaphragmatic sites in 17 (6.9%). Advanced age, B symptoms,
      increased ESR, low lymphocyte and platelet counts, as well as advanced
      pathological stage and lymphocyte depletion histology were common presenting
      features of these patients. 7 patients with infradiaphragmatic disease had
      isolated involvement of inguinofemoral nodes ("peripheral" group) and 10 had only
      intraabdominal disease ("central" group). Clinical characteristics of patients
      with "central" forms were different from those with supradiaphragmatic disease,
      but no differences were observed between "peripheral" infradiaphragmatic and
      supradiaphragmatic groups. Complete remission was achieved in the 82.2% of
      patients with infradiaphragmatic disease. Overall survival was 68% at 5 years,
      and disease-free survival was 74%. No statistically significant differences were
      observed in complete remission rates, survival, and disease-free survival when
      supradiaphragmatic, "central" infradiaphragmatic and "peripheral"
      infradiaphragmatic forms were compared.

PMID- 1988306
TI  - Imipenem-cilastatin for empirical therapy in neutropenic patients with fever: an
      open study in patients with hematologic malignancies.
AB  - In adult neutropenic patients with hematological malignancies, we explored
      imipenem-cilastatin as empirical antibiotic therapy in a dose of 500 mg four
      times daily. Changing to second-line treatment was only resorted to if clinical
      deterioration, new infections or recurrence of fever occurred. A clinically or
      microbiologically documented infection was apparent in 115 of 150 episodes
      studied (76.7%). Imipenem-cilastatin was successful in 70.7% of all episodes and
      in 67.8% of all proven infections. Modification was necessary and successful in
      22.0% of all episodes. 11 patients died while still febrile, 6 of them by
      infection (4%) and 5 because of progressive disease (3.3%). Imipenem-cilastatin
      is safe initial therapy in neutropenic febrile patients.

PMID- 1988307
TI  - Giant plasma cell myeloma--report of three unusual cases.

PMID- 1988308
TI  - Improved response to chemotherapy after interferon alpha-2b in angioimmunoblastic
      lymphadenopathy (AILD)

PMID- 1988310
TI  - Bone marrow examination in non-Hodgkin's lymphoma: comparison of the diagnostic
      value of marrow aspirations and trephine biopsy.

PMID- 1988309
TI  - The expression of 22-kD subunit of cytochrome b558 in patients with X-linked
      chronic granulomatous disease.

PMID- 1988311
TI  - Interstitial lung disease in lymphoproliferative disorders.

PMID- 1988312
TI  - Recombinant alpha 2b interferon (alpha-2b-IFN), chlorambucil, and prednisone in
      advanced chronic lymphocytic leukemia (CLL)

PMID- 1988313
TI  - Cholesterol, lipoprotein and phospholipid levels in acute lymphoblastic
      leukaemia.

PMID- 1988314
TI  - Dipyridamole in vitro suppresses the generation of T-cell cytotoxic functions:
      synergistic activity with cyclosporine.
AB  - The pharmacological activity of dipyridamole has been related to its ability to
      increase intracellular cAMP. Elevated cAMP concentrations can tone down T-cell
      effector functions. The aim of this study was to evaluate the dipyridamole effect
      in vitro on the generation of alloreactive cytotoxic and lymphokine-activated
      killer cells in normal T-cell subpopulations. Dipyridamole suppressed T-cell
      cytotoxic functions in a dose-dependent way. The kinetics of suppression showed
      that dipyridamole prevented the first step of cytotoxicity, i.e. activation of
      the lytic program following allogeneic or interleukin-2 stimulation. The ability
      of dipyridamole to interact with the immunosuppressive activity of cyclosporine
      was also investigated. By itself, cyclosporine suppressed the generation of
      alloreactive cytotoxicity, but not the generation of lymphokine-activated killer
      cells. A synergistic immunosuppressive activity between dipyridamole and
      cyclosporine was observed on the generation of alloreactive cytotoxic T
      lymphocytes.

PMID- 1988315
TI  - Peripheral blood plasmacytosis in a patient with infectious mononucleosis-like
      illness.

PMID- 1988316
TI  - Restraint use in acute care: dynamics reach beyond restraints.

PMID- 1988317
TI  - Nursing expertise in the care of the elderly.

PMID- 1988318
TI  - When should staff nurses replicate research studies?

PMID- 1988319
TI  - ANA activity and updates on payment reform and valuation of nursing services.

PMID- 1988320
TI  - Levels of ritodrine hydrochloride in fetal blood and amniotic fluid following
      long-term continuous administration in late pregnancy.
AB  - Placental transfer of ritodrine hydrochloride (ritodrine) was investigated in
      late-pregnant women following continuous infusion. Five volunteer women
      undergoing cesarean section received a total dose of 650-5970 mg of ritodrine for
      8-49 days. After the infusion was discontinued at cesarean section, maternal and
      fetal blood and amniotic fluid were collected for later determinations of
      ritodrine by radioimmunoassay. Maternal serum concentrations of ritodrine were
      between 99.0-332.4 ng/ml. Serum levels of ritodrine in cord artery and vein were
      75.9-250.5 ng/ml and 74.7-213.0 ng/ml, respectively. Ritodrine levels in amniotic
      fluid ranged from 126.0 to 424.0 ng/ml. The concentration of ritodrine in cord
      vein to maternal vein (CV/MV) was 0.695 +/- 0.066 (m +/- SE), while the
      concentration ratio of the amniotic fluid to maternal vein (AF/MV) was 1.719 +/-
      0.211. In the present study of continuous administration of ritodrine, remarkably
      higher concentrations in fetal circulation and amniotic fluid were observed
      compared to those in cases of short-term infusion.

PMID- 1988321
TI  - Ginger treatment of hyperemesis gravidarum.
AB  - Thirty women participated in a double-blind randomized cross-over trial of the
      efficacy of a natural product, the powdered root of ginger (Zingiber officinale),
      and placebo in hyperemesis gravidarum. Three patients had to be withdrawn. Each
      woman swallowed capsules containing either 250 mg ginger or lactose q.i.d. during
      the first 4 days of the treatment period. Interrupted by a 2 days wash-out period
      the alternative medication was given in the second 4-day period. The severity and
      relief of symptoms before and after each period were evaluated by two scoring
      systems. The scores were used for statistical analyses of possible differences.
      Subjectively assessed, 19 women (70.4%) stated preference to the period in which
      ginger, as was later disclosed, had been given (P = 0.003). More objectively
      assessed by relief scores a significantly greater relief of the symptoms was
      found after ginger treatment compared to placebo (P = 0.035). No side effects
      were observed. The possible mutagenic and antimutagenic characters of ginger
      reported in a study of E. coli have not been evaluated with respect to any
      significance in humans. Powdered root of ginger in daily doses of 1 g during 4
      days was better than placebo in diminishing or eliminating the symptoms of
      hyperemesis gravidarum.

PMID- 1988322
TI  - Karyotype and placental structure of first-trimester spontaneous abortions: a
      morphometrical study.
AB  - Size of placental villi, thickness and condition of trophoblast, stromal density
      of villi as well as perivillous fibrinoid deposits were used as criteria for
      patho-morphological classification of karyotyped first-trimester spontaneous
      abortions. Significant differences in all the criteria were noted. Diagnostic
      values were verified using discriminant analysis. Using morphological values, 67%
      of the cases could be grouped correctly. Including further criteria (week of
      gestation, age of mother) it was possible to improve this to 72%. Normal karotype
      and trisomy could be accurately diagnosed using morphology; however, it is not
      suitable for finding monosomy X and tetraploidy.

PMID- 1988323
TI  - Umbilical artery flow velocity waveforms during spinal anesthesia.
AB  - The umbilical artery Doppler flow velocity waveform was recorded during spinal
      anaesthesia prior to elective caesarean section in 15 uncomplicated pregnancies.
      Although spinal anaesthesia was associated with a significant fall in maternal
      systolic and diastolic blood pressure, there was no change in the umbilical
      artery Pulsatility Index either after preloading the maternal circulation with
      750-1000 ml of Hartman's solution or for the first 15 min after subarachnoid
      injection of 0.5% bupivacaine. The fetal heart rate fell after preloading the
      maternal circulation, but was unchanged by the administration of bupivacaine.
      There was a weak negative correlation between fetal heart and the umbilical
      artery Pulsatility Index. These observations suggest that in normal pregnancy,
      spinal anaesthesia has no detrimental effect on the umbilical artery Pulsatility
      Index.

PMID- 1988324
TI  - Influence of the mode of delivery on initiation of breast-feeding.
AB  - The initiation and the prevalence of breast-feeding after discharge from hospital
      was investigated in 370 singleton parturients and compared to the mode of
      delivery. Infants delivered by vacuum extraction or by caesarean section started
      suckling later, they were more often given formula prescription during the first
      4 days, they were less often breast-fed during the night, and their mother's milk
      'came in' later, but it did not affect the prevalence of breast-feeding after
      discharge. A sleepy infant, which was not very willing to suckle, was the most
      frequent nursing-problem mentioned by the mothers 4 days after delivery. Failure
      to start breast-feeding occurred in only 2.2% of the women, and after 6 months
      52% were still breast-feeding their children.

PMID- 1988325
TI  - The vaginal pH and leucocyte/epithelial cell ratio vary during normal menstrual
      cycles.
AB  - A higher proportion white blood cells (WBC) than vaginal epithelial cells in wet
      smears has been accepted as a sign which, together with clinical signs, can be
      useful in the diagnosis of infections in the genital tract such as cervicitis or
      salpingitis. However, little is known about the normal variation among healthy
      women without any symptoms or signs of genital-tract infection. By taking
      frequent wet smears from three healthy asymptomatic women during four menstrual
      cycles we found that vaginal leucocytosis usually occurred once each cycle.
      Normal vaginal leucocytosis must thus be taken into consideration when evaluating
      wet smear of patients for genital tract infections.

PMID- 1988326
TI  - Prevalence of infertility: international data and problems of measurement.
AB  - This paper discusses the various research options open for measuring the
      prevalence of infertility. National and regional surveys are both population
      based studies but with different methodological approaches. National surveys give
      information on the various parameters of a couple's reproductive life and
      indicate the main trends concerning infertility. They give an approximate
      estimate of the prevalence of infertility, depending on the validity of the
      collected data. Regional studies can measure the prevalence, incidence, causes
      and distribution of primary and secondary infertility. When properly carried out,
      i.e., when the census of infertile couples can be considered as almost exhaustive
      and when the population studied is representative of the general population,
      their results can then be inferred on a national scale. Epidemiologists working
      in infertility have a duty to design appropriate methodologies, thus making
      public health policymakers aware of the aspects and implications of different
      types of infertility surveys.

PMID- 1988327
TI  - Hypertrophic cardiomyopathy and pregnancy: a report of three cases.
AB  - In this paper three pregnancies in association with hypertrophic cardiomyopathy
      are reported. Management of pregnancy and delivery are discussed based upon
      recommendations in literature.

PMID- 1988328
TI  - Antenatal fetal death in twin pregnancies: a dangerous condition mainly for the
      surviving co-twin; a report of four cases.
AB  - The outcome of four twin pregnancies with fetal death of one twin during the late
      second and the third trimester is described. A review of the complications
      occurring after antepartal fetal death of one twin is presented. A management
      plan for this rare complication of pregnancy is established.

PMID- 1988329
TI  - Delayed interval delivery in a triplet pregnancy; a case report.
AB  - A case report is presented in which a triplet pregnancy ended in an immature
      delivery of triplet A at 20 weeks gestation, followed by a successful delay in
      delivery of 49 days of triplets B and C by means of a cervical cerclage and
      tocolysis. This is the first reported case in which two living infants could be
      vaginally delivered after a preceding vaginal delivery of the third infant in a
      triplet pregnancy.

PMID- 1988330
TI  - Human acardiac anomaly: a report of three cases.
AB  - We report on three cases of acardia, all of which had to be classified as
      acardius anceps. The degree of cardiac malformation ranged between a completely
      missing heart and a malrotation of a relatively well-developed heart. One fetus
      showed an intermediate form of cardiac malformation with a hypoplastic cor
      triloculare. Our findings suggest that the defect in cardiac development may take
      place at different times in early embryogenesis, resulting in differing degrees
      of cardiac malformation.

PMID- 1988331
TI  - The effect of short-term heat stress on uterine contractility, fetal heart rate
      and fetal movements at late pregnancy.
AB  - The effects of short-term, moderate heat stress (20 min, 70 degrees C) on uterine
      contractility, fetal heart rate and fetal movements were investigated in 23
      healthy subjects 36 to 37 weeks pregnant. The thermal stress caused minimal
      uterine contractility in five subjects but did not induce labor. Fetal heart rate
      increased from 146 beats per minute to a maximum of 157 beats per minute (P less
      than 0.05) by 10 min after termination of thermal stress. Fetal movements
      increased from 2.3 per minute to 4.9 per minute 35 minutes after heat stress (P
      less than 0.05). Throughout the experiment fetal heart rate variability remained
      normal but in four cases the tracings were temporarily non-reactive during or
      after the heat stress. The newborn infants were all in good condition at delivery
      which, generally, took place at the estimated time of delivery. The results
      suggest that moderate thermal stress does not induce regular uterine
      contractility nor is it harmful to the fetus at late pregnancy.

PMID- 1988332
TI  - Distribution of cholesterol between vesicles and micelles in human gallbladder
      bile: influence of treatment with chenodeoxycholic acid and ursodeoxycholic acid.
AB  - The present study aimed at determining the relative distribution of cholesterol
      between the vesicular and micellar phases in gallbladder bile of gallstone
      patients (n = 23) and gallstone-free subjects (n = 7). Nine of the gallstone
      patients were treated with chenodeoxycholic acid and seven were treated with
      ursodeoxycholic acid, 15 mg/kg/day, for 3 wk before cholecystectomy. The
      vesicular and micellar fractions in bile were separated by sucrose density
      gradient ultracentrifugation, and a clear separation between the two phases was
      obtained. The vesicles were further identified by quasielastic light scattering
      spectroscopy and appeared to be of a uniform size with a mean hydrodynamic radius
      of 760 A. The proportion of cholesterol in the vesicular fraction was
      significantly higher in the untreated gallstone group (40% +/- 4%) compared with
      the gallstone-free (28% +/- 3%), ursodeoxycholic acid (28% +/- 3%) and
      chenodeoxycholic acid (18% +/- 4%) groups. Despite a low cholesterol saturation
      of bile in the latter three groups (88% +/- 12%, 51% +/- 9% and 65% +/- 5%,
      respectively), a considerable part of the biliary cholesterol was carried in the
      vesicular fraction. The cholesterol/phospholipid ratio in the vesicular fraction
      averaged between 0.49 and 0.58 in the gallstone, gallstone-free and
      chenodeoxycholic acid groups, whereas the ursodeoxycholic acid group had a
      significantly lower ratio of 0.24. The nucleation time of bile from the gallstone
      group was short (2 +/- 1 days) compared with the gallstone-free, chenodeoxycholic
      acid and ursodeoxycholic acid groups (23 +/- 3, 24 +/- 6 and 14 +/- 3 days,
      respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1988333
TI  - Prophylactic sclerotherapy for esophageal varices: long-term results of a single
      center trial.
AB  - Survival after prophylactic sclerotherapy was assessed in a single-center study
      involving 99 cirrhotic (41 alcoholic) patients enrolled over 8-yr. The wedged
      hepatic vein pressure gradient was measured; those with pressure greater than or
      equal to 12 mm Hg were randomized to receive sclerotherapy or no treatment. The
      rest were not randomized. Patients in all three groups who bled were treated with
      emergency endoscopy and sclerotherapy. Stratification according to presence of
      ascites was also undertaken. Median follow-up was 61 mo (range = 14 to 107 mo).
      Survival among unrandomized patients was significantly longer than among
      randomized patients (p less than 0.006), but there was no significant difference
      between those treated by sclerotherapy and the controls (p = 0.27). Alcoholic
      cirrhotic patients undergoing sclerotherapy had better 2-yr survival than did the
      controls (80% vs. 43%; p = 0.09), but this benefit was not sustained at 5 yr.
      Survival in the nonalcoholic patient groups was identical. Only 10 of 50 deaths
      were caused by variceal bleeding. Forty-eight percent of patients with large
      varices bled, compared with 20% of patients with small varices. Wedged hepatic
      vein pressure less than 12 mm Hg accurately identified alcoholic patients at low
      risk of variceal bleeding but not nonalcoholic patients. Only four episodes of
      variceal bleeding were attributable to elective sclerotherapy. We conclude that
      in our population, prophylactic sclerotherapy alone does not improve survival.
      The discrepancy in survival between alcoholic and nonalcoholic cirrhotic patients
      suggests that factors other than variceal hemorrhage may be responsible for the
      difference.

PMID- 1988334
TI  - Dual association of HLA DR2 and DR3 with primary sclerosing cholangitis.
AB  - Human leukocyte antigen typing was performed in 81 patients with primary
      sclerosing cholangitis to investigate reported associations between human
      leukocyte antigen type and this disease. The results showed a significant
      increase in the frequency of the antigens B8 and DR3 compared with controls (53%
      vs. 23%, p less than 0.0005, and 56% vs. 21%, p less than 0.0005). This was
      caused by a significant rise in the frequency of the human leukocyte antigen A1
      B8 DR3 haplotype (32 of 81 patients, 40% vs. 12 of 100 patients, 12%, p less than
      0.0005). By contrast, a significant reduction was seen in the frequency of the
      antigens B44 and DR4 (12% vs. 31%, p less than 0.005, and 12% vs. 34%, p less
      than 0.001, pc less than 0.011) because of the complete absence of the B44 DR4
      haplotype in the patient group (p = 0.027, Fisher's exact test). When all the DR3
      positive individuals (including the DR2/DR3 heterozygotes) were eliminated, a
      significant secondary association with DR2 was noted, 25 (69%) of 36 remaining
      patients being DR2-positive compared with 27 (34%) of 79 DR3 negative controls (p
      less than 0.0005, pc less than 0.006). Only 9% of the patients were DR2-positive
      and DR3-positive. Kaplan-Meier analysis demonstrated that survival was not
      influenced by the presence of either haplotype nor by the individual antigens.
      Patients who were DR3-positive were first seen at a significantly younger age
      than those who were DR2-positive (mean ages = 33 yr and 44 yr, respectively, p
      less than 0.002, Student's t test).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1988335
TI  - Localization of epidermal growth factor receptor in hepatocyte nuclei.
AB  - Experiments undertaken to investigate the binding of epidermal growth factor by
      hepatocyte nuclei showed that: (a) isolated nuclei from both normal and
      regenerating rat liver are capable of binding 125I-epidermal growth factor, (b)
      the nuclear epidermal growth factor-binding protein is similar in molecular
      weight to the plasma membrane epidermal growth factor receptor, (c) monoclonal
      antibodies produced against the plasma membrane epidermal growth factor receptor
      recognize the nuclear epidermal growth factor receptor and (d) the nuclear
      receptor has an affinity for epidermal growth factor comparable to that of the
      plasma membrane receptor, but fewer (approximately 10%) nuclear receptors are
      available per protein unit compared with the plasma membrane.

PMID- 1988336
TI  - Hepatic histological findings after transplantation for chronic hepatitis B virus
      infection, including a unique pattern of fibrosing cholestatic hepatitis.
AB  - Long-term follow-up of 27 patients with hepatitis B virus-related chronic liver
      disease treated by transplantation showed that 23 had hepatitis B virus
      recurrence. In 13 patients late changes in the grafts were similar to those
      described in other series: minor abnormalities in five cases, chronic active
      hepatitis in five cases and non-hepatitis B virus-related graft dysfunction in
      three cases. Three patients had incomplete histological follow-up. Analysis of
      the histological changes and viral antigen expression in six cases revealed a
      distinct and novel pattern termed fibrosing cholestatic hepatitis. Development of
      fibrosing cholestatic hepatitis was associated with rapidly progressive graft
      dysfunction. It is postulated that this pattern of fibrosing cholestatic
      hepatitis develops because of a high cytoplasmic expression of viral antigens,
      including HBsAg. The remaining case had some features of fibrosing cholestatic
      hepatitis. The main histological features of this unique syndrome include thin,
      perisinusoidal bands of fibrosis extending from portal tracts to surround plates
      of ductular-type epithelium; prominent cholestasis; ground-glass transformation;
      and ballooning of hepatocytes with cell loss and mild mixed inflammatory
      reaction.

PMID- 1988337
TI  - Assay of hepatitis B virus DNA by polymerase chain reaction and its relationship
      to pre-S- and S-encoded viral surface antigens.
AB  - The polymerase chain reaction was evaluated as a diagnostic tool in 72 chronic
      hepatitis B virus carriers. Hepatitis B virus DNA was detectable in the serum of
      HBsAg-positive virus carriers using aliquots as small as 100 al. The detection
      limit for cloned hepatitis B virus DNA was 100 ag. Primer pairs for different
      regions of the HBV genome resulted in different sensitivity. Detection of the
      amplified hepatitis B virus DNA by Southern blotting and subsequent scintillation
      counting or densitometry allowed a semiquantitative assay. Using several primer
      pairs in parallel for optimal detection, all HBeAg-positive HBsAg carriers, 80%
      of HBe antibody-positive symptomatic HBsAg carriers and 57% of asymptomatic HBe
      antibody-positive HBsAg carriers were found to have hepatitis B virus DNA in the
      serum. During antiviral therapy hepatitis B virus DNA disappeared by the
      polymerase chain reaction assay in patients who became HBeAg negative, but
      polymerase chain reaction detected a relapse earlier than did the conventional
      dot blot. Pre-S antigens were assayed in serum and liver samples from most
      chronic carriers by enzyme-linked immunosorbent assay and/or immunoblot. Although
      most viremic carriers were strongly positive for pre-S1 and pre-S2 antigens, some
      hepatitis B virus DNA-positive HBsAg carriers did not have detectable pre-S
      antigens, and vice versa. Our data show that assay of hepatitis B virus DNA in
      the serum by polymerase chain reaction is by far more proficient than by dot blot
      and that it cannot be replaced by serological assays of HBeAg or pre-S antigen.

PMID- 1988339
TI  - Hepatology: the state of the journal.

PMID- 1988338
TI  - The cellular basis for liver injury in alpha 1-antitrypsin deficiency.

PMID- 1988340
TI  - The polymerase chain reaction for hepatitis B virus DNA.

PMID- 1988341
TI  - Transgenic approach to hepatitis B virus liver damage.

PMID- 1988342
TI  - New insights into canalicular organic anion secretion.

PMID- 1988343
TI  - Omeprazole and aryl hydrocarbon hydroxylases: should we be worried?

PMID- 1988344
TI  - Detection of cell-CAM 105 in the pericanalicular domain of the rat hepatocyte
      plasma membrane.
AB  - Cell-CAM 105 has been identified as a cell adhesion molecule based on the ability
      of anti-cell-CAM 105 monospecific Fab fragments to inhibit the reaggregation of
      rat hepatocytes. Because of its adhesive properties, it was expected that cell
      CAM 105 would be present on the lateral cell surface where adhesive interactions
      predominate. Paradoxically, however, immunofluorescence analysis of frozen
      sections of rat liver using specific monoclonal antibodies indicated that cell
      CAM 105 was present exclusively in the bile canalicular domain of the rat
      hepatocyte where there is no intercellular adhesion. To more precisely define the
      in situ localization of cell-CAM 105, immunoperoxidase labeling and electron
      microscopy were used to examine intact and mechanically dissociated liver tissue.
      Results showed that when accessibility was provided by mechanical dissociation of
      perfusion fixed liver tissue, cell-CAM 105 could be detected in the
      pericanalicular region of lateral membranes. In contrast, when hepatocytes were
      labeled after incubation in vitro under conditions used during adhesion assays to
      induce reaggregation, cell-CAM 105 rapidly redistributed to all areas of the
      plasma membrane. Immunofluorescence analysis of primary hepatocyte cultures
      further revealed that cell-CAM 105 and two other bile canalicular proteins
      relocalized to discrete domains reminiscent of bile canaliculi, whereas cell-CAM
      105 was also present in areas of intercellular contact. Serial section electron
      microscopy analysis of well-defined, cross-sectional profiles of bile canaliculi
      suggested the presence of cell-CAM 105-positive membrane folds that extended
      along the length of the bile canalicular border. In sections from livers in which
      calcium-dependent adhesive contacts had been disrupted by treatment with
      ethylenediamine tetraacetate, intact bile canaliculi were found that remained
      attached only by these border folds. The implications of these results are
      discussed with regard to a possible role for cell-CAM 105 in bile canalicular
      formation.

PMID- 1988345
TI  - Hepatic extraction of organic anions in the rat depends on ligand hydrophobicity.
AB  - Non-bile-salt cholephilic organic anions are efficiently taken up by the liver.
      Recent work from our group has suggested the possible importance of relative
      hydrophobicity among various organic anions in hepatic uptake. To further
      validate and clarify this, we studied hepatic extraction of five different
      cholephilic dyes using the isolated perfused rat liver in single-pass mode.
      Albumin binding affinities and capacities for each of the ligands were measured
      in vitro to permit evaluation of in vivo interactions for each of them over a
      spectrum of unbound ligand concentrations. As expected, a strong positive
      correlation was found between ligand hydrophobicity and the relative degree of
      albumin binding affinity and capacity. Using appropriate experimental conditions,
      we also found a strong positive correlation between hepatic extraction efficiency
      for a given ligand and both its hydrophobicity and its unbound concentration.
      These data indicate that where the unbound ligand concentration is significant,
      the greater the ligand hydrophobicity, the greater is its efficiency of hepatic
      extraction. We conclude that hepatic extraction efficiency for non-bile-salt
      cholephilic organic anions depends on a combination of ligand
      hydrophilic/hydrophobic balance and the availability of the unbound ligand for
      uptake.

PMID- 1988346
TI  - Specificity of the hepatocyte Na(+)-dependent taurocholate transporter: influence
      of side chain length and charge.
AB  - Trihydroxy bile acids with differing nonsterol chain length and charge were
      synthesized to define the effect of these parameters on the ability to
      competitively inhibit the Na(+)-dependent uptake of 14C taurocholate into
      isolated rat hepatocytes. Compounds with long side chains (greater than or equal
      to 0.8 nm) beyond carbon-17 of the sterol nucleus and carrying a negative charge
      or no charge were potent inhibitors. Introduction of a positive charge into the
      side chain weakened inhibition. When the length of the chain beyond carbon-17
      fell below about 0.7 nm, charge still influenced inhibitory potency, but the
      effect was reversed and positively-charged chains yielded slightly greater
      inhibition than negatively-charged chains. From these results one may postulate a
      positively-charged cell surface domain extending outward from a point about 0.7
      nm from the sterol nucleus receptor region. Up to about 0.7 nm from the sterol
      nucleus receptor region one might postulate a negative cell surface charge to
      account for the weaker inhibitory potency of compounds with short negatively
      charged chains. Nonetheless, a short chain, regardless of charge, weakened
      inhibition, suggesting that a long negatively-charged side chain is necessary to
      orient the sterol moiety for optimal receptor fit. These data confirm that the
      Na(+)-dependent taurocholate transport site is sensitive to alterations of side
      chain charge and length and emphasize the importance of structure when designing
      bile acid analogs to probe taurocholate transport mechanisms.

PMID- 1988347
TI  - Separation of periportal and perivenous rat hepatocytes by fluorescence-activated
      cell sorting: confirmation with colloidal gold as an exogenous marker.
AB  - Periportal and perivenous hepatocytes are known to display various functional
      differences. In this study we present a new method to separate periportal and
      perivenous cells: after selectively loading zone 1 or zone 3 with the fluorescent
      label acridine orange in an antegrade or retrograde perfusion, respectively, we
      separated the isolated hepatocytes on a fluorescence-activated cell sorter. The
      common way to check on proper separation is to estimate activities of enzymes
      known to exhibit a heterogeneous acinar distribution. Using enzyme
      histochemistry, however, we found that already on short collagenase perfusion,
      some enzymes displayed a more shallow gradient than in vivo, making enzyme
      activities less suitable as zonal markers. We therefore used colloidal gold
      granules (17 nm) injected intravenously (2.5 mg) into the rat 2 to 3 hr before
      cell isolation. The gold is taken up predominantly by perivenous hepatocytes,
      probably because of the efficient removal of gold granules in zone 1 by competing
      Kupffer cells. We compared acridine orange fluorescence, presence of gold
      particles and activities of six marker enzymes, three biochemically and three
      histochemically determined. Acridine orange and gold both pointed to a high
      enrichment of the fractions, whereas most enzyme activities were more randomly
      distributed among the cells as a result of the isolation procedure. Our
      separation procedure yielded fractions highly enriched in either viable
      periportal or perivenous cells, both from one liver. The use of colloidal gold as
      a marker to monitor separation is a valuable alternative to the more risky
      estimation of enzyme activities.

PMID- 1988349
TI  - What consumers want in a pediatrician.
AB  - Hospital administrators are seeking to identify and address unmet consumer
      demand. The following data compare consumer demand for pediatricians with the
      characteristics that pediatricians are making available to their prospective
      patients in eight major markets. The data source is Prologue, a service of
      Consumer Health Services Inc., Boulder, CO. Prologue provides health care
      information to consumers and marketing information and services to hospitals and
      physicians. Each month, Prologue handles 100,000 consumer calls and schedules
      more than 20,000 appointments with physicians; this data base is the source of
      the consumer information in the accompanying figures. The physician information
      comes from Prologue's data base of more than 10,000 participating physicians in
      more than 45 specialties.

PMID- 1988348
TI  - Kupffer cell activation and endothelial cell damage after storage of rat livers:
      effects of reperfusion.
AB  - Reperfusion injury characterized by loss of endothelial cell viability occurs
      after cold ischemic storage of livers for transplantation surgery. Here,
      ultrastructural changes in stored rat livers were examined by scanning and
      transmission electron microscopy. With increasing times of storage in Euro
      Collins solution (4 to 24 hr) followed by 15 min of reperfusion at 37 degrees C,
      a sequence of structural alterations was observed involving endothelial and
      Kupffer cells. Widening of endothelial fenestrations occurred after 4 hr and
      progressed over 8 to 24 hr to retraction of cellular processes, ball-like
      rounding, sinusoidal denudation and ultrastructural derangements consistent with
      loss of cell viability. Kupffer cells exhibited progressive rounding, ruffling of
      the cell surface, polarization, appearance of wormlike densities, vacuolization
      and degranulation over a similar time course. By contrast, the structures of
      parenchymal and fat-storing cells were relatively undisturbed by cold storage and
      reperfusion. Alterations to endothelial and Kupffer cells were also studied as a
      function of time of reperfusion. After 24 hr of storage, endothelial cells showed
      retraction of cytoplasm before reperfusion that progressed quickly to loss of
      viability and denudation during reperfusion. Kupffer cell activation (ruffling,
      degranulation) during reperfusion was slower and occurred after deterioration of
      endothelial cells. Livers stored in Euro-Collins solution were also compared with
      livers stored in University of Wisconsin cold storage solution, an improved
      preservation medium for transplantation. University of Wisconsin solution
      provided better preservation of endothelial structure and markedly reduced
      parenchymal cell blebbing and swelling before reperfusion. University of
      Wisconsin solution also reduced Kupffer cell activation and release of lysosomal
      enzymes. In conclusion, endothelial cell deterioration followed by Kupffer cell
      activation occurred after increasing times of cold ischemic storage and
      reperfusion of rat livers. Both changes may contribute to the pathophysiology of
      graft failure caused by reperfusion-mediated storage injury.

PMID- 1988350
TI  - Hospitals' use of contract management approaches 50%.
AB  - Hospital CEOs are evenly split on the issue of whether to contract with outside
      firms to manage departments in their facilities. Although a small majority have
      never used contractors, the number of executives employing contract managers is
      growing--and executives are pleased with the results. These are just a few of the
      results of Hospitals' recent survey of 1,100 hospital CEOs nationwide. The survey
      asked executives for information about their hospitals' use of more than 40
      specific services, including "hotel," business and clinical contract services.
      Our survey is one of only a few major studies ever undertaken that have asked
      hospitals themselves about their use of contract-management services. And what
      were they looking for? Interestingly, not economic advantage but specialized
      expertise.

PMID- 1988351
TI  - Hospitals work to provide advance directives information.
AB  - With a deadline of Dec. 1 looming ahead of them, hospitals are beginning to
      prepare for compliance with a new federal law on advance directives. The Patient
      Self-Determination Act, passed as part of the federal budget last year, requires
      those institutions participating in Medicare and Medicaid to give information on
      advance directives for care. Beginning on that date, hospitals will have to ask
      whether every patient they admit has an advance directive--a living will or a
      durable power of attorney for health care.

PMID- 1988352
TI  - Net patient revenues lag behind increases in expenses.
AB  - Total net patient revenues for the nation's hospitals lagged behind increases in
      expenses during the first nine months of 1990, according to data from the
      American Hospital Association's National Hospital Panel Survey. And hospitals in
      some regions, particularly in the Northeast, saw more troubling performance than
      others. Meanwhile, the number of inpatient days dropped 1.1 percent during the
      same period.

PMID- 1988353
TI  - Ambulatory care growth changes CEO priorities.

PMID- 1988354
TI  - Examining hospital board-CEO relations.

PMID- 1988355
TI  - Study: hospitals want to compare uniform data.

PMID- 1988356
TI  - Does health care spending hurt U.S. competitiveness?

PMID- 1988357
TI  - Who generates top dollars per inpatient admission?

PMID- 1988358
TI  - In a weak economy, REITs (real estate investment trusts) stand out as capital
      source.

PMID- 1988360
TI  - Policy-makers and MDs must work together.

PMID- 1988359
TI  - New technique opens window to heart and brain.

PMID- 1988361
TI  - Normal tissue reactivity of four anti-tumor monoclonal antibodies of clinical
      interest.
AB  - Normal tissue reactivity on frozen sections was examined with 4 monoclonal
      antibodies (MAbs) that were reported previously to be negative or weakly reactive
      with normal tissues, and strongly reactive with some types of carcinoma. All 4
      antibodies reacted strongly with certain normal epithelial cells. The antibodies
      tested include 2 antibodies to ovarian cancer, MOv18 and MOv19, one antibody to
      breast cancer, H23, and one antibody reactive with a range of carcinomas, B72.3.
      MOv18, MOv19 and H23 reacted with many normal glandular and ductal epithelial
      cells, while B72.3 reacted most strongly with secretions of the small intestine
      epithelium and the suprabasal squamous epithelial cells of the esophagus. Since
      the tissue distribution of MOv19 was very similar to that of another antibody
      described previously, MW207, these two antibodies were compared by competitive
      binding inhibition, and found to recognize the same epitope. Our data emphasize
      the importance of repeated, independent tests of antibody specificity.

PMID- 1988362
TI  - Carcinoma-associated mucin serum markers CA M26 and CA M29: efficacy in detecting
      and monitoring patients with cancer of the breast, colon, ovary, endometrium and
      cervix.
AB  - Two recently developed monoclonal antibody (MAb)-based anti-mucin assays, CA M26
      and CA M29, were studied in 250 cancer patients and compared to 3 well
      established marker tests, viz., CA 125, CA 15.3 and SCC, in order to assess their
      clinical usefulness as serum tumor markers. Pre-treatment sera were obtained from
      patients with predominantly low-stage epithelial malignancies comprising 200
      adenocarcinomas (of the ovary, endometrium, breast and large intestine) and 50
      squamous-cell carcinomas (of the uterine cervix). Pretreatment sera of 50
      patients with benign ovarian tumors were included to evaluate levels in benign
      disease, CA M26 and CA M29 cut-off levels were established in 89 healthy
      controls. In patients with adenocarcinomas, overall positivity for CA M29 was
      24%, ranging from 10% in breast cancer to 60% in ovarian cancer. Overall
      positivity was highest for CA 125 (30%) and lowest for CA M26 (18%) with CA M29
      (24%) being similar to CA 15.3 (25%). In adenocarcinomas the combined CA M26-CA
      M29 assays equalled results obtained with the CA 125-CA 15.3 combination (33% vs.
      36%). Elevation of 2 or more markers was highly indicative of advanced disease (p
      less than 0.025). A majority of positive patients showed either CA M26 or CA M29
      elevations, indicating that both antibodies detect distinct epitopes. After
      adjustment for tumor site and stage, the profile of CA M26 as a single marker
      differed significantly from the profiles of CA 125 and of CA M29. CA M26 was
      frequently (32%) elevated in patients with squamous-cell carcinoma of the cervix
      and CA M26 levels were often independently elevated. CA M26 seems to be valuable
      as an additional marker in breast cancer and perhaps as a new marker in cervical
      cancer. CA M29 may be useful in ovarian cancer in addition to CA 125.

PMID- 1988363
TI  - Blood group and blood-group-related antigens in normal pancreas and pancreas
      cancer: enhanced expression of precursor type 1, Tn and sialyl-Tn in pancreas
      cancer.
AB  - Expression of blood-group antigens A, B, Le(a), sialyl-Le(a) (sLe(a)), Le(b),
      Le(x), Le(y), precursor type I, Tn and sialyl-Tn (sTn) was examined in non
      neoplastic pancreas (n = 37) and pancreas cancer (n = 21) using mouse monoclonal
      antibodies (MAbs). Immunohistochemical assays were performed on sections of
      paraffin-embedded tissues using the avidin-biotin complex method. In normal
      pancreas, antibodies detecting Le(a), sLe(a) and Tn reacted with ductal
      epithelium, and antibodies detecting A and B reacted with acini and ducts,
      independently of secretor status. Le(x) was weakly expressed in ducts and acini,
      and sTn could not be detected in normal pancreas. Expression of Le(b), Le(y) and
      precursor type I was regulated by secretor status: Le(b) and Le(y) were expressed
      in ducts of secretor and Le(a-b-) individuals, but not in ducts of non-secretors;
      precursor type I was weakly expressed in acini and ducts of non-secretors and
      Le(a-b-) individuals, and was absent in acini and ducts of secretors. The
      following alterations in the expression of blood-group antigens were observed in
      pancreas cancer: (1) enhanced expression of Le(x), Tn and sTn; (2) enhanced
      expression of precursor type I independently of secretor status; (3) loss of
      regulation of Le(b) by the secretor gene; (4) decreased expression of Le(y). The
      weak expression of precursor type I. Tn and sTn in non-neoplastic pancreas, and
      their stronger expression in pancreas cancer, suggests that up-regulation of
      their expression is associated with malignant transformation of pancreatic duct
      cells.

PMID- 1988364
TI  - Cancer incidence among parents of patients with colorectal cancer.
AB  - To investigate the genetic factor in the development of colorectal cancer, a
      cohort study was undertaken of parents of patients with this disease. All 1,524
      patients, who were diagnosed with colorectal cancer in Denmark in 1982-84 and
      were below the age of 60 years, were selected from the National Cancer Register.
      The parents of these patients were identified from the public population
      registers. The index persons had a total of 1,478 eligible mothers, of whom 96%
      were successfully traced, and a total of 1,414 eligible fathers, of whom 96% were
      traced. These parents were sought in the Cancer Register for cancer cases
      diagnosed in the period January 1, 1943 to December 31, 1986. The incidence rates
      for the Danish population were used to estimate the expected numbers of
      colorectal cancer cases among the parents. Both the mothers and the fathers
      exhibited an increased risk of colorectal cancer. The standardized incidence
      ratios were 1.62 (95% CI 1.31-2.01) and 1.87 (95% CI 1.54-2.27), respectively. In
      a previous study we found that spouses of patients with colorectal cancer in
      Denmark did not have an increased risk of this disease. The increased risk found
      in the present study among the parents of patients therefore indicates that a
      possible genetic factor is present in the aetiology of colorectal cancer, and
      that it is of importance in the general population.

PMID- 1988365
TI  - Coffee consumption and bladder cancer risk.
AB  - The relationship between coffee drinking and the risk of bladder cancer was
      analyzed within the framework of a French hospital-based case-control study
      conducted between 1984 and 1987, which included 690 cases of histologically
      confirmed bladder cancer (599 males and 91 females), and 690 age-, sex- and
      hospital-matched controls. To dissociate the effects of smoking and coffee
      drinking among males, the analysis of the male group was restricted to 2
      contrasted subgroups: non-smokers on the one hand, and current smokers and
      inhalers of black tobacco cigarettes on the other. Coffee drinking was found to
      be significantly associated with the risk of bladder cancer among men in both
      groups and the increase in the risk was dose-dependent (OR = 1, 2.9, 5.1
      respectively, for drinking 1, 2, greater than or equal to 3 cups of coffee per
      day among non-smokers, and 1, 2.5 and 3.0 respectively, for drinking 1-4, 5-7,
      greater than cups among smokers). This result was not observed for women.

PMID- 1988366
TI  - Regional heterogeneity in breast carcinoma: thymidine labelling index, steroid
      hormone receptors, DNA ploidy.
AB  - We examined multiple samples of 65 primary breast carcinomas larger than 1 cm in
      diameter for thymidine labelling index (TLI), DNA index (DNAI, a measure of
      cellular DNA content by flow cytometry), and estrogen (ER) and progesterone (PgR)
      receptors by radioligand-binding. One or more axillary metastases were also
      assayed in 11 patients. Two to 15 samples were successfully assayed for TLI from
      59 tumors, 2-31 samples for DNAI from 61 tumors, and 2-15 samples from 55 tumors
      for ER and PgR. Criteria for heterogeneity were excess inter-sample variance in
      comparison with intrasample variance at the p less than 0.05 level for TLI and
      DNAI, and variation of clinically significant magnitude in assay results for ER
      and PgR. Sixty-one percent of tumors were heterogeneous for TLI, 26% for DNAI,
      24% for ER and 40% for PgR. High TLI disposed toward heterogeneity for TLI itself
      (p = 0.06), for ER (p = 0.04), and for PgR (p = 0.007). Young age favored
      heterogeneity for TLI (p = 0.12), ER (p = 0.002), and PgR (p = 0.04).
      Heterogeneity for DNAI was not related to age and TLI status but was more common
      in larger tumors (p = 0.08). After consideration of relationships between TLI,
      age, size, ER and PgR, TLI rather than age appears to be the more important
      determinant of heterogeneity for receptors. High TLI could lead to heterogeneity
      through increased numbers of cell divisions that favor emergence of variant
      stemlines, or by causing local vascular and humoral disparities through rapid
      growth. Regional heterogeneity can explain erroneous prognostic predictions in
      approximately 10% to 20% of breast carcinoma patients. We recommend multiple
      sampling of large breast carcinomas and analysis of axillary metastases for study
      of tumor markers.

PMID- 1988367
TI  - Histological and urinary reactivity of monoclonal antibody 1BE12 in bladder
      carcinoma. Purification of the antigen from urine.
AB  - We have previously reported the production of monoclonal antibody (MAb) 1BE12,
      which recognizes a glycoprotein in breast-cancer cells. In the present work,
      1BE12 reactivity was tested by immunohistochemistry in bladder carcinoma (92
      cases) and in non-tumoral bladder samples (15 cases). In 71% of bladder tumors,
      more than 30% of cells were intensely stained by 1BE12. The percentage of
      reactive cells was higher in cancers invading the muscle than in more superficial
      tumors (p = 0.039). In non-tumoral bladder, immuno-staining, when present, was
      usually confined to the superficial layers with a low number of cells stained
      (less than 30%) in 13/15 cases. Slot blots, performed on urine samples from 43
      bladder-cancer patients and 21 healthy controls, were quantified by densitometry
      scanning. We found higher optical density (OD) values in urine from muscle
      invasive-cancer patients than in urine from more superficial tumors and healthy
      controls, with a significantly different distribution (p = 0.005). The urinary
      antigen was detected by immunoblotting with 1BE12 as high-molecular-weight
      species (greater than 150 kDa). The reactive glycoprotein could thus be purified
      by immunoaffinity and FPLC filtration from the perchloric-acid-soluble fraction
      of urine from patients with invasive bladder carcinoma. The availability of
      purified antigen will allow us to quantitate our assay, in order to evaluate its
      potential use as a prognostic indicator in bladder-cancer patients.

PMID- 1988368
TI  - Decreased tumorigenicity of a transplantable rat sarcoma following transfer and
      expression of an IL-2 cDNA.
AB  - The notion that tumour-cell-derived IL-2 might lead to paracrine stimulation of
      the host anti-tumour response was tested in a transplantable rat sarcoma model.
      Three HSNLV clones induced to secrete different amounts of human IL-2 following
      retroviral gene transfer showed reduced tumorigenicity and metastatic potential
      in athymic (nu/nu) and immunocompetent syngeneic rats which was directly related
      to the level of IL-2 secretion. In contrast, the tumorigenicity of HSNLV clones
      secreting a biologically inactive form of IL-2 (IL-2Lys20) was unaltered. T
      lymphocyte-mediated rejection of ZipI, the highest IL-2 producer, was
      demonstrated histologically in hooded rats and infiltrating mononuclear cells
      were also observed in ZipI tumours growing in athymic rats. Tumours derived from
      IL-2-secreting HSNLV showed reduced or absent IL-2 secretion in immunocompetent
      rats, sometimes with associated loss of the IL-2 provirus, but continued to
      secrete IL-2 in nude rats. The host response to Moloney-helper-virus-infected
      HSNLV was also examined and the results represent a cautionary note to those
      undertaking experiments of a similar nature.

PMID- 1988369
TI  - Skin fibroblast cell lines derived from non-Hodgkin's-lymphoma (NHL) patients
      show increased sensitivity to chronic gamma irradiation.
AB  - Cultured fibroblast cells from 19 patients with non-Hodgkin's lymphoma (NHL), 3
      patients with ataxia telangiectasia (AT), 3 AT heterozygotes and 11 (presumed)
      normal subjects were studied for impaired colony-forming ability after chronic
      gamma irradiation. Five cell lines from the NHL patients were also examined for
      the sensitivity to acute gamma irradiation, as compared with those of normal
      subjects. To ascertain the degree of radiosensitivity of different cell lines, a
      comparison was made of the D10 values (radiation dose resulting in 10% survival)
      for each cell line, estimated "by eye" from the actual survival curves, and also
      from the calculated curves fitted to a log-linear model. It was observed that the
      acute gamma irradiation failed to show any appreciable difference in the
      radiation response of the cell lines from NHL patients as compared with those of
      normal subjects. However, chronic irradiation demonstrated significantly
      increased radiosensitivity in at least 10-12 NHL patients with a p value of less
      than 0.05, when the D10 values of each patient's cell line were compared with the
      calculated composite values for the normals. When the D10 values of the NHL
      patients and the normal subjects were compared as 2 groups, the former appeared
      to be significantly more sensitive to chronic gamma irradiation (p less than
      0.0001). The same level of significant difference in radiosensitivity was found
      between the 2 groups when their D37 values (radiation dose resulting in 37%
      survival) were compared. In general, the radiation response of the NHL patients
      was similar to that of the AT homozygotes and heterozygotes used as a positive
      control group. Our data thus show that increased radiosensitivity is associated
      with the NHL patients studied, indicating an underlying abnormality of their DNA
      repair.

PMID- 1988370
TI  - Detergent extraction and characterization of tumor hemolytic factor from plasma
      membranes of oncogene transformed fibroblasts.
AB  - Cancer cells have the capacity to lyse erythrocytes by a cell-contact-requiring
      phenomenon. Subcellular fractionation procedures have revealed that the hemolytic
      principle resides in the cancer cell plasma membrane. In this study we report the
      detergent extraction of a potent hemolytic factor from the plasma membranes of
      ras-oncogene-transformed fibroblasts. Ammonium-sulfate partitioning (60-100%) of
      detergent-extracted proteins was used to enrich hemolytic activity. Tumor
      membrane Hemolytic Factor (mTHF) was inactivated by treatment with papain,
      suggesting that it is a protein. mTHF was inhibited by serum, but was unaffected
      by extremes of temperature and pH, also by metal chelation with EDTA. Surface
      radio-iodination of tumor cells and isolation of cell organelles was used to
      characterize the outer plasma membrane localization of mTHF. mTHF retained
      hemolytic activity when reconstituted into stable phospholipid vesicles. Pre
      incubation of mTHF with red cell ghosts led to an abrogation of hemolytic
      activity. mTHF-induced hemolysis consists of a 2-stage phenomenon: an early
      binding step, followed by hemolysis after 4 hr.

PMID- 1988371
TI  - Treatment of leukemia L1210 and P388 by arabinosylcytosine-polysaccharide
      conjugates.
AB  - Conjugates of 1-beta-D-arabinofuranosylcytosine (araC) with two polysaccharides
      such as polygalacturonic acid (PGA) and carboxymethylated yeast beta-D-glucan
      (CMG) were tested for their antileukemic activity in vitro on a L1210 cell line
      in suspension culture, in soft agar assay and in vivo on L1210, L1210/araC- and
      P388-leukemia-bearing mice. Both conjugates showed high activity in vitro in soft
      agar assay, compared with araC. Single administration of PGA-araC or CMG-araC
      increased the survival time 1.5 x or 1.7 x, respectively, compared with araC in
      vivo in L1210-leukemia-bearing mice. The conjugates were not active against araC
      resistant leukemia line L1210/araC. The marked effect of both PGA-araC and CMG
      araC against leukemia L1210 and P388 is probably due to the prolonged release of
      free araC from conjugates caused by hydrolysis.

PMID- 1988372
TI  - Oncofetal mucin M1 epitope family: characterization and expression during colonic
      carcinogenesis.
AB  - The gastric mucin M1 antigens, markers associated with colonic carcinogenesis,
      have been characterized by new antimucin monoclonal antibodies (MAbs). These
      MAbs, obtained against mucins isolated from a human ovarian mucinous cyst (MAbs
      19M1, 21M1 and 45M1) and from a pancreatic adenocarcinoma (MAb 96RA), were
      compared with 5 other anti-M1 mucin MAbs described previously, which
      characterized the a, b, c, d and e mucin M1 epitopes. Using immunoperoxidase,
      these new MAbs exclusively stained the surface gastric epithelium of normal human
      gastro-intestinal tract and reacted with fetal, precancerous and cancerous
      colonic mucosa, but not with normal colon. Immunoradiofixation studies showed
      that these new MAbs are directed against 3 epitopes (f, g and h) which are
      different from the a, b, c, d and e mucin M1 epitopes, though present on the same
      a immunoreactive high-molecular-weight components (greater than 1,000 kDa) with a
      density of 1.4 by CsCl-density-gradient ultracentrifugation. M1 antigenicity is
      characterized by a family of 8 different M1 epitopes which were destroyed with
      beta-mercaptoethanol (except for the f epitope), sensitive to a 5 hr trypsin
      treatment and resistant to 5 mM periodate (except for the h epitope). Some
      epitopes (b, c and d) showed increasing immunoreactivity after 20 mM periodate
      treatment, suggesting cryptic location. In rat-colon adenocarcinomas, M1 mucin
      epitopes were masked but could be decrypted using high periodate treatment,
      similar to normal rat gastric mucosa, thus suggesting the absence of drastic
      changes in the saccharide coat of the peptide mucin portion bearing M1 epitopes.
      Cryptic location, periodate resistance, sensitivity to protease and
      conformational behavior strongly suggest that the peptidic core of gastric (or
      fetal colonic) mucin plays a role in M1 immunoreactivity. Indeed, the resurgence
      of M1 antigens during colonic carcinogenesis is due to re-expression of the
      peptide core of gastric (or fetal colonic) mucins.

PMID- 1988373
TI  - Endocrine characteristics of early menarche.

PMID- 1988374
TI  - The relationship between breast cancer and polyunsaturated fatty acids.

PMID- 1988375
TI  - Psychiatric nursing for the 1990s: new concepts, new theories.

PMID- 1988376
TI  - Therapeutic use of metaphors.
AB  - This article focuses on the use of metaphors or story-telling as a technique in
      psychotherapy with individuals, couples, and families. It includes samples of
      various metaphors, indications for their use, and specific examples from clinical
      practice that demonstrate therapeutic potential and impact. In keeping with
      nursing's humanistic and client-centered values, one should remember that the
      best use of technique occurs within the context of meaningful interpersonal
      process, which is the essence of a therapeutic nurse-client relationship.

PMID- 1988377
TI  - A comparison of wife abuse between two cultures: perceptions, attitudes, nature,
      and extent.
AB  - The purpose of this study was to explore the similarities and differences between
      Anglo-American and Mexican-American battered women. This descriptive study
      compared a group of 25 Anglo-American and 25 Mexican-American women over age 18
      who had been physically abused by their husbands at least two times and had
      resided in shelters for battered women. This study addressed the nature,
      severity, and frequency of wife abuse; women's perception of what they consider
      wife abuse; and their attitudes toward wife abuse. Respondents were matched for
      age and socioeconomic status. Data were collected through personal interviews,
      using a semistructured interview schedule consisting of three instruments. Data
      were analyzed using descriptive statistics. Comparisons between the two groups
      were done using t test and chi-square procedures. A Type I error probability
      level of less than .05 was used to determine statistical significance. Results
      showed that there were more similarities than differences in the manifestation of
      wife abuse between the two groups. However, Anglo-American women perceived more
      types of behavior as being abusive and exhibited a less tolerant attitude toward
      wife abuse than did Mexican-American women. The t test results indicated no
      significant difference in the severity and frequency of wife abuse between Anglo
      Americans and Mexican-Americans.

PMID- 1988378
TI  - A concept analysis of intimacy.
AB  - This concept analysis examines how the concept of intimacy has been defined in
      the scholarly literature in order to determine what characteristics or necessary
      conditions exist that differentiate this phenomenon from all other phenomena. The
      objective of this concept analysis is to derive a theoretical definition of
      intimacy that can then be used to operationalize the concept for research.
      Intimacy is of significance to psychiatric nursing theory because (a) intimacy
      has been identified as being important to the psychosocial development of adults;
      (b) intimacy plays a developmental role in identity formation, through the
      consensual validation of personal worth by providing individuals with the
      opportunity to feel understood and accepted as they are, within the relationship;
      (c) research indicates that married couples reporting a deficiency or an absence
      of intimacy have a significantly higher proportion of symptoms of a nonpsychotic
      emotional illness; (d) failure to develop intimacy in relationships has been
      identified as one of the most common factors for seeking outpatient
      psychotherapy; and (e) intimacy has been identified as a key component in
      individuals' satisfaction with their social support. The theoretical definition
      for intimacy is this: a quality of a relationship in which the individuals must
      have reciprocal feelings of trust and emotional closeness toward each other and
      are able to openly communicate thoughts and feelings with each other. The
      conditions that must be met for intimacy to occur include reciprocity of trust,
      emotional closeness, and self-disclosure. As the literature does not uniformly
      incorporate physical intimacy as a necessary condition for the concept of
      intimacy, physical closeness was not incorporated into the definition.

PMID- 1988379
TI  - Toward a new conceptualization of women's anger.
AB  - Most theorizing about women's anger has been based on cases of troubled women who
      sought psychotherapy. However, theories derived from clinical practice have
      subsequently been phrased in terms of women in general, with no disclaimer
      regarding their origin. Empirical evidence refutes many widely accepted
      assumptions and theories about women's anger. In this article, the hydraulic
      model of emotion is rejected, and existential and cognitive-behavioral theories
      are used as the basis for a new middle-range theory of women's anger. Both trait
      anger (general propensity to become angry) and modes of anger expression are
      included in the model. Appraisal concepts, modifying factors, and outcome
      variables are described. The model awaits use by clinicians and validation by
      researchers in the 1990s.

PMID- 1988380
TI  - King's theory of goal attainment applied in group therapy for inpatient juvenile
      sexual offenders, maximum security state offenders, and community parolees, using
      visual aids.
AB  - Group psychotherapy has been considered the treatment of choice by many
      therapists working with offenders within the criminal justice system. However,
      there has been little written by nurses regarding this special population. This
      article's purpose is to illustrate how King's theory of goal attainment may be
      used in conducting group psychotherapy with offender populations. The application
      of King's model is demonstrated in three milieus: an inpatient setting for
      juvenile sexual offenders, a state maximum security prison, and a halfway house
      for offenders involved in a work-release program. The methodology and use of
      visual aids in actualizing King's theory of mutual goal setting and goal
      attainment are discussed.

PMID- 1988381
TI  - Problem-solving group therapy: two inpatient models based on level of
      functioning.
AB  - Hospitalized psychiatric patients frequently have deficits in their problem
      solving abilities. An inpatient problem-solving group provides a therapeutic
      experience in which patients learn and apply the problem-solving process to
      practical and interpersonal difficulties they are presently experiencing. Two
      problem-solving group models, derived from cognitive-behavior theory, are
      suggested to accommodate diverse levels of inpatient functioning. Implications
      for nursing practice and recommendations are addressed.

PMID- 1988382
TI  - Group psychotherapy in an acute inpatient setting: techniques that nourish self
      esteem.
AB  - This article describes a conceptual model and reparative techniques used in group
      therapy in a 15-bed acute inpatient psychiatric unit located in a 340-bed
      metropolitan trauma center. The group meets daily for 1 hr. The population
      reflects patients suffering from chronic mental illness and polysubstance abuse
      and those adapting to such complex medical problems as AIDS, spinal cord
      injuries, burns, and so forth. Using Roy and Roberts's (1981) adaptive modes of
      self-concept and interdependency, I describe how narcissism, the psychic
      structure designed to protect, repair, and restore the wounded self-esteem
      (Stolorow & Lachman, 1980), sustains group adaptations at the pregroup level.
      Lonergon (1980) described the pregroup phase as "parallel talk." It is similar to
      "parallel play" and generally reflects the developmental arrest or adaptive
      regression of individual group members. At this stage, group membership consists
      of a collection of individuals who use each other as an audience to whom they can
      express their narcissistic needs. Often, repeated blows to the patient's self
      esteem result in a pervasive sense of powerlessness and helplessness. Patients
      gradually lose touch with their "real self" and become increasingly dependent on
      external cues to determine their feelings and behavior. The adaptive narcissistic
      need to depend on other people to feel whole suggests that group therapy can be a
      powerful tool in treating patients who suffer profound wounds to the self-esteem,
      prevalent in the population described. The reparative techniques used by the
      group therapist to initiate group involvement require the ability to tolerate and
      value a continuous pregroup phase. The patient with narcissistic behavior both
      craves and undermines attempts at group involvement.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1988383
TI  - Comparative effects of sexual assault on sexual functioning of child sexual abuse
      survivors and others.
AB  - This study quantitatively and qualitatively examined the effects of sexual
      assault on the sexual functioning of 37 sexually active women an average of 8.21
      years postevent (Mdn = 4.08 years). More than 80% of the sample reported some
      sexual dysfunction with a partner as a result of the assault. Greatest impairment
      was reported by subjects who either had a history of child sexual abuse or had no
      prior sexual victimization before the current assault as compared with subjects
      who had prior sexual assaults. When data were examined by type of perpetrator,
      adverse effects were greatest for subjects assaulted by a health care
      professional. Qualitative analysis revealed that, for the total sample, greatest
      effects were in the area of adverse feeling states (part of desire dysfunction)
      as early response inhibitors, with subjects who had a history of child sexual
      abuse being the only group to report orgasmic dysfunction and guilt. There was no
      statistically significant difference in sexual dysfunction between subjects who
      filed civil suits and those who did not. Implications for treatment are
      discussed.

PMID- 1988384
TI  - The art, science, and techniques of reframing in psychiatric mental health
      nursing.
AB  - Reframing is a powerful psychotherapeutic intervention. Changing the "frame" in
      which a person perceives events can change the meaning the person associates with
      the events. This article describes several types of reframing strategies that
      have been developed within the context of a model of human behavior and
      communication known as neurolinguistic programming (NLP). Fundamental assumptions
      of the NLP model are discussed and several reframing techniques are described. A
      set of strategies that clinicians can use to redefine behaviors and expand a
      client's model of the world are illustrated. Development of theoretical and
      clinical applications of the NLP model and reframing techniques in psychiatric
      mental health nursing is an important task for the 1990s.

PMID- 1988385
TI  - Myocardial infarction prognostic scoring system.
AB  - A myocardial infarction prognostic scoring system for patients treated in a
      coronary care unit is described. The prognostic significance of 22 variables, all
      which were available on admission, were analyzed. A prognostic index was then
      constructed by a modified stepwise logistic regressional analysis technique. The
      variables that were used in the scoring system were Killip hemodynamic class,
      infarct location, and the maximal ST segment elevation in a single lead. The
      scoring system was validated in an independent group of patients, including a
      group of patients treated with intravenous streptokinase. The scoring system may
      prove to be useful for individual patient prognostication and management
      strategies, and for the quantification of infarct severity for use in clinical
      studies.

PMID- 1988386
TI  - Attitudes and knowledge of nurses regarding organ procurement.
AB  - The purpose of this study was to examine nurses' attitudes and knowledge
      regarding organ procurement. Nurses in critical care areas completed a
      questionnaire designed to elicit their attitudes toward and knowledge of organ
      donation. Differences were found between the unit in which nurses worked and the
      extent to which they would participate in care of a patient for organ donation.
      Significant relationships were found between the fact that a nurse had previously
      cared for donors and the degree of comfort felt in obtaining consent, extent to
      which the nurse would participate in care, and knowledge of organ procurement
      procedures. The nurses' feelings regarding donation and their degree of comfort
      in obtaining consent were correlated positively with higher knowledge scores.
      Knowledge deficits were identified in all areas. Results indicated that although
      most nurses were supportive of organ procurement, there were aspects with which
      they were uncomfortable and others in which they lacked knowledge. The study
      revealed the need for additional awareness and education of nurses in all areas
      of the organ donation process.

PMID- 1988387
TI  - Reciprocal or pseudoreciprocal rhythm?

PMID- 1988388
TI  - Electrode site preparation techniques: a follow-up study.
AB  - A posttest-only control group design was used to study the effect of electrode
      site preparation techniques on reducing electrical potential across a pair of
      disposable skin electrodes. One hundred twenty healthy volunteers were randomly
      assigned into one control and three treatment groups of 30 subjects each. The
      three treatments were One Step Skin Prep used once, ECG Prep Pad used five times,
      and ECG Prep Pad used once. To control for handedness, the skin preparation site
      was randomly assigned to either the left or right forearm. One-tailed paired t
      test analyses were used to compare differences between treatment arms and control
      arms within each group (p less than 0.05). Skin preparation done by using One
      Step Skin Prep or the ECG Prep Pads used once significantly decreased skin
      potentials by 2.3 mV and 3.3 mV respectively. There was no significant difference
      in the control group and the group in which ECG Prep Pads were used five times.
      These findings extend the knowledge of techniques available to reduce the amount
      of noise (electrical potential) in physiologic measurement using skin electrodes.

PMID- 1988389
TI  - Wellness motivation in cardiac rehabilitation.
AB  - Lack of patient adherence to prescribed regimens is a fundamental problem in
      cardiac rehabilitation programs. A causative factor in lack of patient adherence
      may be related to failure to address differences in individual health behavior
      motivation in cardiac rehabilitation. A group of 52 patients who had had
      myocardial infarction were sampled to test the relationship between social
      support systems, health locus of control, health value orientations, and wellness
      motivation. Pearson correlation coefficients indicated significant positive
      correlations between health locus of control variables, health value orientation
      variations, and wellness motivation. Health locus of control and health value
      orientation variables entered into a multiple regression equation to explain 32%
      of the variation in wellness motivation. Awareness of individual motivational
      responses that influence health behaviors in cardiac rehabilitation may enable
      nurses to develop intervention strategies for patients with cardiovascular
      disease who would benefit from modifying their risk-producing life-styles.

PMID- 1988390
TI  - Interpleural analgesia.
AB  - Postoperative pain relief is necessary not only for patient comfort, but also to
      facilitate ventilation and ambulation. The use of opioid analgesia, either
      intravenously, intramuscularly, or intraspinally, may be ineffective and can
      cause respiratory depression. The administration of local anesthetics into the
      pleural space is a technique of providing analgesia of rapid onset and long
      duration. This analgesia is accomplished without causing the respiratory
      depression or sedation associated with the use of opioids. Because innovative
      analgesic methods are often selected for critically ill patients presenting after
      surgery in the intensive care setting, critical care nurses may encounter
      patients receiving local anesthetics administered via interpleural catheter.

PMID- 1988391
TI  - Drug administration in relation to meals in the institutional setting.
AB  - To investigate adherence to literature recommendations for administration of five
      cardiovascular drugs in relation to mealtimes, data from records of 183 adult
      patients in two short-term and two long-term care settings were tabulated. Ninety
      three percent of patients taking quinidine sulfate and 85% of patients taking the
      other four study drugs received one or more doses incorrectly. Findings show that
      timing recommendations for dosing in relation to meals are not considered in
      these institutions when drug administration schedules are established. The
      practice of arbitrary schedule selection could have serious consequences,
      including adverse physiologic and financial impact on the patient from loss of
      therapeutic effectiveness or development of drug toxicosis. Medication schedules
      need to be designed to achieve the greatest drug bioavailability.

PMID- 1988392
TI  - Development of a special care unit for chronically critically ill patients.
AB  - Intensive care units (ICUs) are recognized as one of the most expensive services
      provided by hospitals. Within these ICUs are a growing population of patients
      whose stays are extensively prolonged because of complications or underlying
      chronic health conditions that are exacerbated by a critical illness. These
      patients can be described as "chronically critically ill" and are costly to
      hospitals both in terms of actual dollars and in terms of the burden of care to
      nurses and physicians. This article describes the creation of a special care unit
      (SCU) designed specifically to meet the needs of chronically critically ill
      patients. The SCU environment is composed of a physical design that accommodates
      limited technology and care aimed at family involvement and rehabilitation, a
      case management practice model, and a shared governance management model. This
      structure is in contrast to traditional ICU environments, which include physical
      layouts that allow for high technology and close monitoring of patients, a
      primary nursing delivery system, and a bureaucratic management model. A research
      project to compare the effects of the SCU with the effects of the traditional
      ICUs on nurse and patient outcomes is described.

PMID- 1988393
TI  - Stress experience of spouses of patients having coronary artery bypass during
      hospitalization and 6 weeks after discharge.
AB  - The purpose of this study was to describe stress process variables in spouses of
      patients having coronary artery bypass surgery during hospitalization (T1) and 6
      weeks after discharge (T2). Problems and concerns of spouses at T1 and T2 and
      spouse perceptions of nurse support were also addressed. Eighty-six women
      participated in the study at T1 and 67 women participated at T2. Data were
      collected by self-report instruments and open-ended questions. Women reported an
      average number of family life changes and high levels of social support at T1 and
      T2. Women perceived their husband's illness severity at the extreme end of the
      continuum at T1 and T2. Physical and mental symptoms of stress were high at T1
      but significantly less at T2. Marital quality was average at T1 but significantly
      less at T2. Hospital environment, lack of information, and family members were
      frequently reported to make hospitalization more difficult. Husband's self-care
      activities, uncertainty, and husband's physical and mental symptoms were concerns
      that spouses frequently reported at T2.

PMID- 1988394
TI  - Health locus of control and helpfulness of prayer.
AB  - The purpose of this study was to examine the relationship between health locus of
      control and helpfulness of prayer as a direct-action coping mechanism in patients
      before having cardiac surgery. The Multidimensional Health Locus of Control
      Scales and the investigator-developed Helpfulness of Prayer Scale were issued to
      100 subjects 1 day before cardiac surgery. Ninety-six subjects indicated that
      prayer was used as a coping mechanism in dealing with the stress of cardiac
      surgery, and 70 of these subjects gave it the highest possible rating on the
      Helpfulness of Prayer Scale. No relationship was found between health locus of
      control and helpfulness of prayer. Individuals of each locus orientation
      perceived prayer to be helpful. Findings suggest that prayer is perceived as a
      helpful, direct-action coping mechanism and warrants support by health personnel.
      It is recommended that further research explore the effect of prayer on patients'
      ability to cope with stressful situations.

PMID- 1988395
TI  - Support of patient autonomy in the do not resuscitate decision.
AB  - In this study we examined critical care nurses' beliefs concerning the support of
      patient autonomy in the do not resuscitate (DNR) decision. The study sample
      consisted of 251 members of the American Association of Critical-Care Nurses
      (AACN). Subjects were asked to examine four hypothetical cases and select the
      agent (patient, family member, physician, or nurse) (1) most appropriate to
      support patient autonomy in the DNR decision and (2) who would actually make the
      DNR decision, if these hypothetical cases were to occur on the clinical units
      where the subjects were employed. The nurses' answers concerning the agent best
      able to support patient autonomy in the DNR decision were in general agreement
      with the do not resuscitate decision model developed by the principal
      investigator (B.B.O.) to demonstrate support for patient autonomy in the DNR
      decision. However, when asked who would actually make the DNR decision on their
      units, the nurses frequently responded that the physician would make the
      decision, regardless of the agent selected as best able to support patient
      autonomy in the case situation. An ethical conflict concerning the DNR decision
      appeared to exist for the majority of the subjects in this study.

PMID- 1988396
TI  - Treatment strategies in shock: use of oxygen transport measurements.
AB  - Shock has traditionally been categorized according to its cause. Shock can result
      from hemorrhage, primary cardiac failure, central nervous system failure, trauma,
      or sepsis. Therapeutic principles have been developed for each etiologic type.
      End points for such therapy have included optimization of pulmonary capillary
      wedge pressure, cardiac output, blood pressure, and urine output. Recent
      investigators agree that the common denominator in each of the shock syndromes is
      a reduction in the amount of oxygen consumed by the cell. The logical therapeutic
      approach would be to increase oxygen delivery to support the increased metabolic
      demand of the cells. The end point of resuscitation should be optimization of
      oxygen delivery and oxygen consumption. These variables are easily calculated by
      using data obtained from pulmonary artery catheter and laboratory measurements.
      The physician or nurse caring for critical ill patients should have a thorough
      understanding of the rationale for the use of oxygen transport calculations and
      the methods of manipulating oxygen delivery. A simple explanation of these
      principles including the importance of hemoglobin, cardiac index, and percent
      saturation of hemoglobin and suggested treatment strategies are presented.

PMID- 1988397
TI  - Malassezia furfur fungemia associated with central venous catheter lipid emulsion
      infusion.
AB  - Malassezia furfur has been associated with fungemias in infants after prolonged
      intravenous lipid emulsion alimentation. Most cases of M. furfur fungemia
      reported in the literature involved neonates and required catheter removal for
      cure. M. furfur is probably an underreported problem in neonates as well as
      adults with central venous catheters, receiving lipid emulsions, because the
      organism requires selective enrichment media for growth, for example, Sabouraud's
      dextrose agar with sterile olive oil overlay. This case report of M. furfur
      fungemia in a neonates is unique because the neonate recovered on discontinuation
      of the lipid emulsion, without removal of the central venous catheter.

PMID- 1988399
TI  - Don't forget the pilot work!

PMID- 1988398
TI  - Is phase 2 cardiac rehabilitation necessary for early recovery of patients with
      cardiac disease? A randomized, controlled study.
AB  - In this study the effects of rehabilitation teaching plus exercise testing on
      perceived self-efficacy for and performance of daily activities were compared
      with and without exercise training. Subjects were patients who had had myocardial
      infarction or cardiac surgery (mean age 57.7 +/- 11.3 years) and who had already
      received inpatient rehabilitation services. Subjects were randomly assigned to
      one of three groups. Treatment group 1 (n = 11) received teaching, treadmill
      exercise testing, and exercise training (three times weekly for 5 weeks).
      Treatment group 2 (n = 15) received only teaching and exercise testing. The
      control group (n = 14) received only routine care without supervised exercise or
      teaching. Measurements of self-efficacy and activity performance were made at
      hospital discharge and at 4 and 9 weeks after the cardiac event. Repeated
      measures analysis of variance showed an increase in self-efficacy scores (p less
      than 0.001) and performance of physical activity (p less than 0.001) for all
      groups. Both treatment groups, especially the training group, obtained the
      highest scores, but differences between groups were nonsignificant (p greater
      than 0.05). These results indicate that in a sample of uncomplicated, motivated
      patients who had participated in a phase 1 inpatient rehabilitation program,
      substantial improvements in self-efficacy and performance of daily activities
      were made early in recovery, before the onset of phase 2, formalized outpatient
      therapy.

PMID- 1988400
TI  - Technology assessment in critical care.

PMID- 1988401
TI  - Myocardial infarction in the young adult.
AB  - CAD in young male adults below the age of 40 years has generally been found to be
      associated with the usual risk factors associated with CAD. In a lesser number of
      young adults, MIs may be related to cocaine use. Sympathomimetic effects and
      increase in myocardial oxygen demand are factors considered responsible for acute
      MI in cocaine-abusing patients. In young adults who are asymptomatic following an
      acute MI and who are able to pass treadmill exercise stress tests at levels of
      Bruce stage 4 have been shown to have normal coronary arteriograms. Thus this
      subset should not require routine coronary angiograms following an acute MI.

PMID- 1988403
TI  - Marquest SCT 2000 heated humidifier.

PMID- 1988402
TI  - Effects of auditory stimuli on comatose patients with head injury.

PMID- 1988404
TI  - Risks from Baxter Multifuge and other centrifuges without safety latches.

PMID- 1988406
TI  - Physio-control Lifepak 10 defibrillator/monitor Sync mode.

PMID- 1988405
TI  - Rehabilitation and home care services: a return to the hospital setting.

PMID- 1988407
TI  - Medex disposable pressure transducers used with a Mennen Horizon 3000 physiologic
      monitor.

PMID- 1988408
TI  - Ungrounded receptacles on the Olympus TC-V1 video cart.

PMID- 1988409
TI  - Ambulation aids.

PMID- 1988410
TI  - Profoundly different professions: commentary on prescribing privileges for
      psychologists.

PMID- 1988411
TI  - Buspirone augmentation of fluoxetine in patients with obsessive compulsive
      disorder.
AB  - Twenty patients with obsessive compulsive disorder were treated openly with
      fluoxetine for 20 weeks. In 10 of the patients, addition of buspirone during the
      last 8 weeks improved clinical response. The role of augmenting strategies is
      discussed.

PMID- 1988412
TI  - Psychiatric complications during flooding therapy for posttraumatic stress
      disorder.
AB  - The authors use six case vignettes to illustrate underrecognized complications
      occurring during flooding therapy for posttraumatic stress disorder (PTSD),
      including exacerbation of depression, relapse of alcoholism, and precipitation of
      panic disorder. A common denominator to the majority of these cases appears to be
      the mobilization of negative posttrauma appraisal, accompanied by shame, guilt,
      and anger. The authors suggest that flooding may not be helpful for these
      negative emotions in the manner that it is for anxiety. Suggestions for
      preventing and treating complications of flooding therapy for PTSD include
      employing more cognitive forms of therapy in cases at risk; supporting abstinence
      from alcohol and other substances; providing adjunctive pharmacologic treatment
      as indicated, e.g., tricyclics for depression or panic; and providing long-term
      follow-up.

PMID- 1988413
TI  - A case report of cimetidine-induced clozapine toxicity.
AB  - Cimetidine may decrease concomitant medication clearance by inhibiting the
      oxidative system of cytochrome P-450. The authors report increased serum
      clozapine levels and adverse side effects during clozapine and cimetidine
      treatment but not during clozapine and ranitidine treatment in a patient with
      chronic paranoid schizophrenia.

PMID- 1988414
TI  - Effect of phenytoin on plasma clozapine concentrations in two patients.
AB  - Little is known about interactions of other drugs with the recently marketed
      antipsychotic clozapine. Two cases in which the addition of phenytoin caused a
      decrease in plasma clozapine concentrations and worsening of psychoses are
      described, and possible explanations are discussed.

PMID- 1988415
TI  - Fluoxetine treatment of cocaine abuse in heroin addicts.
AB  - The authors administered fluoxetine to 11 cocaine-abusing heroin addicts entered
      in a methadone maintenance program to determine whether it would decrease cocaine
      craving and use. Three patients discontinued treatment within a few days of
      initiation because of lack of any acute therapeutic effect. The remaining 8
      received fluoxetine for at least 1 week and were followed up over 1 to 6 months.
      Of these 8, 5 (63%) were successfully treated for cocaine abuse. Three case
      examples are presented. Fluoxetine may prove a useful addition to the therapeutic
      armamentarium in the treatment of cocaine abuse.

PMID- 1988416
TI  - Buspirone in major depression: a controlled study.
AB  - One hundred and fifty-five outpatients suffering from major depression with
      moderate anxiety entered a double-blind study comparing 8 weeks of treatment with
      buspirone or placebo. Thirty-four percent of buspirone and 41% of placebo
      patients discontinued treatment before 8 weeks. Results were consistent across
      all physician- and patient-completed outcome measures, with treatment response to
      buspirone significantly better than to placebo at treatment endpoint. Seventy
      percent of buspirone and 35% of placebo patients (p less than .01) were rated
      moderately or markedly improved after 8 weeks of therapy. Initial levels of
      anxiety and depression had no significant effect on treatment outcome. Buspirone
      was found to be safe and well tolerated at doses of up to 90 mg/day.

PMID- 1988417
TI  - Pergolide mesylate treatment of cocaine withdrawal.
AB  - Side effects occasionally limit the use of bromocriptine for cocaine withdrawal.
      The recently released medication pergolide shares some pharmacologic properties
      with bromocriptine but differs in potency and dopamine receptor subtype
      specificity. The authors tested pergolide in the treatment of 21 patients
      experiencing cocaine withdrawal. Sixteen patients reported rapid improvement in
      sleep and decreased cocaine craving. Side effects were limited primarily to
      gastrointestinal complaints.

PMID- 1988418
TI  - Fluoxetine treatment of a fetish.

PMID- 1988419
TI  - Bromocriptine and neuroleptic malignant syndrome.

PMID- 1988420
TI  - Potential antidopaminergic effects of serotonin reuptake inhibitors.

PMID- 1988421
TI  - Brain abnormalities in schizophrenia.

PMID- 1988422
TI  - MAOI and monosodium glutamate interaction.

PMID- 1988424
TI  - Cytoplasmic transcription system encoded by vaccinia virus.

PMID- 1988423
TI  - The deep structures of psychology and prescribing: more than a superficial look.

PMID- 1988426
TI  - Production of thrombin by the prothrombinase complex is regulated by membrane
      mediated transport of prothrombin.
AB  - Production of thrombin by phospholipid-bound prothrombinase complexes has been
      described as being regulated by the prothrombin concentration in the buffer (free
      substrate model) as well as by the concentration of prothrombin adsorbed to the
      phospholipid surface (bound-substrate model). We studied simultaneous adsorption
      and conversion of prothrombin on planar bilayers consisting of 20%
      dioleoylphosphatidylserine and 80% dioleoylphosphatidylcholine. A transport
      limitation in the conversion of prothrombin was prevented by using a very low
      (0.3 fmol cm-2) amount of prothrombinase on the bilayer. The Michaelis and
      catalytic constants thus found were Km = 5.8 +/- 0.7 nM and kcat = 33 +/- 1 s-1
      (mean +/- S.D.). The apparent bimolecular rate constant Kcat/Km = 5.7 x 10(9) M-1
      s-1 exceeds the theoretically maximal value for the free-substrate model. In
      contrast, kcat/Km is within the range expected for a diffusion-controlled bound
      substrate model. A similar mechanism for prothrombin conversion in suspensions of
      phospholipid vesicles would imply increasing kcat/Km values for increasing
      vesicle diameter. This prediction was tested and a 3-fold increase in kcat/Km
      values was indeed found for vesicles 60-80 nm in diameter compared to vesicles of
      20-30 nm diameter. It is concluded that thrombin production is dependent on
      protein fluxes rather than on protein concentrations.

PMID- 1988425
TI  - Evidence for leucine zipper motif in lactose repressor protein.
AB  - Amino acid sequence homology between the carboxyl-terminal segment of the lac
      repressor and eukaryotic proteins containing the leucine zipper motif with
      associated basic DNA binding region (bZIP) has been identified. Based on the
      sequence comparisons, site-specific mutations have been generated at two sites
      predicted to participate in oligomer formation based on the three-leucine heptad
      repeat at positions 342, 349, and 356. Leu342----Ala, Leu349----Ala, and Leu349--
      -Pro have been isolated and their oligomeric state and ligand binding properties
      evaluated. These mutant proteins do not form tetramers but exist as stable dimers
      with inducer binding comparable with the wild-type protein. Apparent operator
      affinities for lac repressor proteins with mutations in the proposed bZIP domain
      were significantly lower than the corresponding wild-type values. For these
      dimeric mutant proteins, the monomer-dimer equilibrium is linked to the apparent
      operator binding constant. The values for the monomer-monomer binding constant
      and for the intrinsic operator binding constant for the dimer cannot be resolved
      from measurements of the observed Kd for operator DNA. Further studies on these
      proteins are in progress.

PMID- 1988427
TI  - Effect of temperature on receptor-activated changes in [Ca2+]i and their
      determination using fluorescent probes.
AB  - Several recent studies of intracellular Ca2+ concentration ([Ca2+]i using
      fluorescent indicators have involved experiments performed at nonphysiological
      temperatures, frequently room temperature. In the studies reported here, a
      reduction in temperature was shown to influence the measurement of [Ca2+]i in two
      major ways. The first is an effect on the value for the Kd (apparent dissociation
      constant) used in the calculation of [Ca2+]i. The Kd values for indo-1 and fura-2
      were found to change with temperature in a manner analogous to the related
      compounds [ethylene-bis(oxyethylenenitrilo)]tetraacetic acid and bis-(o
      aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid. Experiments showed that the use
      of previously published Kd values (measured at 37 degrees C) in experiments at
      room temperature results in errors of at least 25% in the calculated [Ca2+]i. The
      second arises from the differential temperature sensitivities of the
      physiological processes that make up any particular value of [Ca2+]i. While
      resting [Ca2+]i was relatively unaffected by reduced temperature (27 degrees C,
      13 degrees C), changes in [Ca2+]i following stimulation were profoundly
      influenced and in a way that was not simply predictable. Analysis of the
      responses indicated that the observed effects resulted largely from a temperature
      dependent reduction in the rate of Ca2+ removal from the cytosol together with an
      additional component, namely a marked reduction in Ca2+ entry, at the lower
      temperature (13 degrees C). The net result was observed as changes in the initial
      rise in [Ca2+]i on stimulation, together with more profound, and complex, effects
      on the sustained elevation in [Ca2+]i following stimulation. This latter
      component was markedly increased at 27 degrees C, but was decreased in cells at
      13 degrees C.

PMID- 1988428
TI  - Importance of the character and configuration of residues B24, B25, and B26 in
      insulin-receptor interactions.
AB  - By use of isolated canine hepatocytes and insulin analogs prepared by trypsin
      catalyzed semisynthesis, we have investigated the importance of the aromatic
      triplet PheB24-PheB25-TyrB26 of the COOH-terminal B-chain domain of insulin in
      directing the affinity of insulin-receptor interactions. Analysis of the receptor
      binding potencies of analogs bearing transpositions or replacements (by Tyr, D
      Tyr or their corresponding 3,5-diiodo derivatives) in this region demonstrates a
      wide divergence in the acceptance both of configurational change (with [D
      TyrB24,PheB26]insulin and [D-TyrB25,PheB26]insulin exhibiting 160 and 0.1% of the
      receptor binding potency of insulin, respectively) and of detailed side chain
      structure (with [TyrB24,PheB26]insulin and [TyrB25,PheB26]insulin exhibiting 2
      and 80% of the receptor binding potency of insulin, respectively). Additional
      experiments addressed the solvent accessibilities of the 4 tyrosine residues of
      insulin and the insulin analogs at selected peptide concentrations by use of
      analytical radioiodination. Whereas two analogs ([TyrB25,PheB26]insulin and [D
      TyrB24,PheB26]insulin) were found to undergo self aggregation, no strict
      correlation was found between the ability of an analog to aggregate and its
      potency for interaction with the insulin receptor. Related findings are discussed
      in terms of the interplay between side chain and main chain structure in the COOH
      terminal domain of the insulin B-chain and the structural attributes of insulin
      that determine the affinity of insulin-receptor interactions.

PMID- 1988429
TI  - The primary structure of human glutaminyl-tRNA synthetase. A highly conserved
      core, amino acid repeat regions, and homologies with translation elongation
      factors.
AB  - We describe the nucleotide sequences of several overlapping cDNA clones specific
      for human glutaminyl-tRNA synthetase. The identified open reading frame indicates
      that the enzyme is composed of 1440 amino acids. A stretch of about 360 amino
      acids of the human enzyme is highly conserved in bacterial and yeast glutaminyl
      tRNA synthetases. However, the human enzyme is three times larger than the
      bacterial and twice as large as the yeast enzyme suggesting that a considerable
      part of human glutaminyl-tRNA synthetase has evolved to perform functions other
      than the charging of tRNA. The sequence outside of the conserved core region
      includes three 57-amino acid repeats followed by a consecutive stretch of 11
      charged amino acids. A computer assisted search of two protein data banks reveals
      that the human glutaminyl-tRNA synthetase shares small blocks of amino acid
      similarities with several other synthetases of different amino acid
      specificities. Interestingly, the enzyme also possesses some regions of
      similarities with eukaryotic translation elongation factor EF-1 but not with any
      other sequence stored in the protein data banks. The coding regions of human and
      mouse glutaminyl-tRNA synthetase cDNAs are identical at 94% of the codons.
      However, the 3'-noncoding regions of mouse and human mRNAs are more divergent
      (approximately 68%) but both possess the potential to form stable secondary
      structures of similar general architecture.

PMID- 1988430
TI  - Partially folded state of the disulfide-reduced N-terminal half-molecule of
      ovotransferrin as a renaturation intermediate.
AB  - A previous report (Hirose, M., Akuta, T., and Takahashi, N. (1989) J. Biol. Chem.
      264, 16867-16872) has shown that for the efficient oxidative refolding of
      disulfide-reduced ovotransferrin, a preincubation under reduced conditions at a
      low temperature is essential. To study the renaturation pathway, the disulfide
      reduced N-terminal half-molecule of ovotransferrin was analyzed by CD spectrum.
      The reduced protein was found to take, at low temperatures, a partially folded
      conformation that can be distinguished from both the native and denatured states.
      The folded protein was in a metastable state with delta GD value of 2.2-2.8
      kcal/mol at 6 degrees C. The conformation was variable depending on temperature
      conditions; its stability was decreased at a lower temperature (1.0-1.2 kcal/mol
      at 0 degrees C). Subsequent reoxidation at 6 degrees C by oxidized glutathione
      led efficiently the reduced protein to the correctly renatured form having the
      iron-binding capacity, indicating that the partially folded state is the
      immediate precursor to subsequent oxidative refolding.

PMID- 1988431
TI  - Processing of DNA base damage by DNA polymerases. Dihydrothymine and beta
      ureidoisobutyric acid as models for instructive and noninstructive lesions.
AB  - The processing of unrepaired DNA lesions is a key to understanding and predicting
      the biological end points of particular DNA damages. In this study, we prepared
      single-stranded f1 phage (f1-K12) DNA containing dihydrothymine or beta
      ureidoisobutyric acid as models for instructive or noninstructive base lesions
      and assessed the potential biological consequences of these lesions in vitro and
      in vivo. To determine the effect of the two lesions on in vitro DNA synthesis,
      the extent of DNA synthesis was measured by 3H-labeled nucleotide incorporation,
      and the newly synthesized DNA was analyzed by DNA sequencing gels. The results
      showed that dihydrothymine in the template was at most a weak block to in vitro
      DNA synthesis catalyzed by Escherichia coli DNA polymerase I Klenow fragment (Pol
      I) and T4 DNA polymerase. In contrast, beta-ureidoisobutyric acid constituted a
      very strong (probably absolute) replicative block in vitro. With Pol I,
      termination bands were observed either opposite or one base prior to (3' to) the
      putative beta-ureidoisobutyric acid depending on its position in the template.
      However, when DNA synthesis was catalyzed by Pol I lacking a 3'----5' exonuclease
      activity, termination bands were only observed opposite beta-ureidoisobutyric
      acid, with purine nucleotides being incorporated preferentially opposite the
      lesion. With T4 DNA polymerase that contains a very active 3'----5' exonuclease
      activity, DNA synthesis was arrested almost exclusively one base prior to (3' to)
      the putative beta-ureidoisobutyric acid site in the template. We also measured
      survival of transfecting DNA containing dihydrothymine or beta-ureidoisobutyric
      acid in an attempt to correlate the in vitro data with in vivo processing. In
      keeping with the results obtained in vitro, dihydrothymine present in
      transfecting f1-K12 DNA did not constitute an inactivating lesion. On the other
      hand, it took 0.9 beta-ureidoisobutyric acid residues per molecule to inactivate
      transfecting f1-K12 DNA, indicating that the lesion was an absolute replicative
      block in vivo. When host cells were ultraviolet-irradiated to induce the SOS
      response, a slight increase (about 2-fold) in survival of transfecting f1-K12 DNA
      containing beta-ureidoisobutyric acid was observed. The potential effects of the
      structures of base lesions on lesion-polymerase interactions are discussed.

PMID- 1988432
TI  - Modulation of interleukin 2 internalization and interleukin 2-dependent cell
      growth by antireceptor antibodies.
AB  - The growth factor interleukin 2 (IL2) binds to and is internalized together with
      high-affinity surface receptors present on lymphoid cells. This endocytosis thus
      results in down-regulation of the receptors. However, it is not known if the
      internalization is relevant to the induction of cell growth. In the present study
      a rat monoclonal antibody to the P55 chain of the IL2 receptor was used to
      examine the role of receptor internalization in the IL2-dependent autocrine human
      tumor T cell line IARC 301. When given alone, this antibody did not inhibit IL2
      binding, internalization, or IL2-dependent cell proliferation. However,
      crosslinking by anti-rat immunoglobulins, which did not affect binding of the
      growth factor, inhibited both IL2 internalization and cell proliferation. Besides
      offering a novel means for the specific inhibition of the uptake of IL2 bound to
      IL2 high-affinity receptors, the results are compatible with the association of
      this receptor-ligand uptake to the growth stimulation by IL2.

PMID- 1988433
TI  - The interaction of histone H5 and its globular domain with core particles,
      depleted chromatosomes, polynucleosomes, and a DNA decamer.
AB  - Certain features of linker histone behavior were analyzed using a precipitation
      and a nitrocellulose filter binding assay. Chromatosomes, depleted of the linker
      histones, present one unique binding site to the globular domain of histone H5
      (GH5) which involves the two 10-base pair DNA ends of the chromatosome.
      Additional binding to lower affinity sites is intrinsically different and results
      in aggregation as does all binding to core particles. These findings, as well as
      the binding study on a synthetic DNA decamer, lend support to earlier hypotheses
      of more than one DNA binding site on the globular domain. Our studies provide a
      deeper insight into the long standing question of H5/nucleosome stoichiometry. A
      salt dependence analysis of GH5 binding to H5-depleted chromatosomes indicates
      that GH5 displaces a number of ions similar to the total H1 linker histone,
      suggesting a delocalized binding of the carboxyl- and amino-terminal tails.

PMID- 1988434
TI  - Cosubstrate binding site of Pseudomonas sp. AK1 gamma-butyrobetaine hydroxylase.
      Interactions with structural analogs of alpha-ketoglutarate.
AB  - Forty-one aromatic and aliphatic analogs of alpha-ketoglutarate were studied
      kinetically for their interaction with the alpha-ketoglutarate binding site of
      gamma-butyrobetaine hydroxylase obtained from Pseudomonas sp. AK1. Together, the
      compounds represent structural permutations probing the contribution of: 1) the
      C5 carboxyl group of alpha-ketoglutarate (domain I); 2) the C1-C2 keto acid
      moiety of alpha-ketoglutarate (domain II); 3) the distance between domains I and
      II; and 4) the spatial relationship of the two domains required for optimal
      interaction with the cosubstrate binding site. All compounds were competitive
      inhibitors for alpha-ketoglutarate (Km 0.018 mM). Functionally, two subsites of
      the cosubstrate binding site were evident: subsite I for polar interaction with
      the C5 carboxyl group, and subsite II, comprising of two distinct cis-oriented
      coordination sites of the catalytic ferrous ion which interact with the C1-C2
      keto acid moiety. The most efficient inhibitors were pyridine 2,4-dicarboxylate
      (Ki 0.0002 mM) and 3,4-dihydroxybenzoate (Ki 0.0006 mM). Both compounds contain a
      carboxyl group and a chelating moiety corresponding to domains I and II of alpha
      ketoglutarate, respectively. The fixed orientation of these groups in both
      analogs was used to assess intersubsite distance and spatial relationship
      required for optimal interaction with the cosubstrate binding site. Binding at
      subsite I and chelation at subsite II were indispensible for effective
      competitive inhibition. The distance between these two domains also helped
      determine whether attachment at the cosubstrate binding site would be
      catalytically productive. This was emphasized by the failure of either
      oxaloacetate or alpha-ketoadipinate to promote hydroxylation. Optimal interdomain
      distance, however, was not sufficient for cosubstrate utilization, as pyridine
      2,4-dicarboxylate, with an interdomain distance identical to alpha-ketoglutarate
      in its staggered conformation, did not sustain hydroxylation. In the overall,
      these studies suggest that alpha-ketoglutarate utilization occurs in a ligand
      reaction at the active site ferrous ion of gamma-butyrobetaine hydroxylase. This
      is of particular interest since the delineated stereochemical mode of oxidative
      decarboxylation could generate the reactive oxo-iron species that was shown
      experimentally to promote gamma-butyrobetaine hydroxylation by an abstraction
      recombination mechanism (Blanchard, J. S., and Englard, S. (1983) Biochemistry
      22, 5922-5928; Englard, S., Blanchard, J. S., and Midelfort, C. F. (1985)
      Biochemistry 24, 1110-1116).

PMID- 1988435
TI  - The conformation of nascent polylysine and polyphenylalanine peptides on
      ribosomes.
AB  - Polypeptide synthesis using either phenylalanine or lysine was initiated on
      Escherichia coli ribosomes; then the position and conformation of the nascent
      peptide were monitored by fluorescence techniques. To this end, fluorophores had
      been attached to the amino terminus of each nascent peptide, and major
      differences were observed as chain extension occurred. Polyphenylalanine appeared
      to build up as a hydrophobic mass adjacent to the peptidyl transferase center
      while polylysine apparently was extended directly from the ribosome into the
      surrounding solution. An explanation for these differences may be provided by the
      physical and chemical properties of each polypeptide. These properties may be
      responsible for the route by which each peptide exits the peptidyl transferase
      center as demonstrated by the different sensitivity of each to inhibition by
      erythromycin.

PMID- 1988436
TI  - 5-Formyltetrahydrofolate polyglutamates are slow tight binding inhibitors of
      serine hydroxymethyltransferase.
AB  - The interaction of the mono- and triglutamate forms of 5-methyltetrahydrofolate
      and 5-formyltetrahydrofolate with serine hydroxymethyltransferase were determined
      by several methods. These methods included: determining dissociation constants by
      observing the absorbance at 502 nm of a ternary complex of the enzyme, glycine,
      and the folate compounds; determining inhibition constants from steady-state
      reactions; and determining the rate of formation and breakdown of the enzyme
      inhibitor complex by rapid reaction kinetics. Studies of the dissociation and
      inhibitor constants showed that both 5-methyltetrahydrofolate and 5
      formyltetrahydrofolate have essentially the same affinity for the enzyme-glycine
      binary complex. However, rapid reaction and steady-state kinetic studies showed
      that the triglutamate form of 5-formyltetrahydrofolate both binds and is released
      much more slowly from the enzyme-glycine binary complex, compared with the
      triglutamate form of 5-methyltetrahydrofolate. The results also showed that only
      one rotamer of 5-formyltetrahydrofolate binds at the active site of serine
      hydroxymethyltransferase. The results are discussed in terms of the possible role
      of 5-formyltetrahydrofolate polyglutamates in regulation of one-carbon
      metabolism.

PMID- 1988437
TI  - Nonhomogeneous labeling of liver mitochondrial acetyl-CoA.
AB  - The specific activity of carbons 1 and 2 of plasma acetoacetate has been used as
      a measure of the specific activity of liver mitochondrial acetyl-CoA in tracer
      studies. To test whether or not acetoacetate actually reflects acetyl-CoA, livers
      were perfused with a mixture of substrates that are converted to mitochondrial
      acetyl-CoA: 1 mM lactate, 0.2 mM pyruvate, 0.2 mM acetate, and, where indicated,
      0.2 mM octanoate or 0.2 mM alpha-ketoisocaproate. In each experiment, one of
      these substrates was 13C-labeled. Labeling of mitochondrial acetyl-CoA was
      assessed by three methods: (i) molar percent enrichment of total tissue acetyl
      CoA; (ii) molar percent enrichment of carbons 4 and 5 of tissue citrate, the
      precursor of which is acetyl-CoA; and (iii) molar percent enrichment of carbons 1
      and 2 of perfusate ketone bodies. Nonhomogeneous labeling of liver mitochondrial
      acetyl-CoA occurred under most conditions, i.e. the enrichments of carbons 4 and
      5 of citrate were different from enrichments of carbons 1 and 2 of ketone bodies.
      Thus, based upon our results obtained in perfused livers, we question the
      validity of measuring the labeling of carbons 1 and 2 of acetoacetate as a
      noninvasive probe of liver mitochondrial acetyl-CoA.

PMID- 1988439
TI  - Identification and characterization of a new member of the prolactin family,
      placental lactogen-I variant.
AB  - This report describes the identification and characterization of a new member of
      the placental prolactin (PRL) family, termed placental lactogen-I variant (PL
      Iv). PL-Iv was isolated from medium conditioned by late gestation placental
      explants. Rat PL-Iv was found to be closely related to rat PL-I. Amino-terminal
      sequence analysis indicated that PL-Iv shared approximately 88% sequence identity
      with the amino terminus of PL-I. PL-Iv proteins cross-reacted with antiserum to
      recombinant mouse PL-I and PL-Iv mRNA hybridized with a PL-I cDNA. Multiple PL-I
      and PL-Iv species were present in placental cytosol. Despite the structural
      similarities between PL-I and PL-Iv, distinct differences were also evident.
      Antibodies generated to the amino-terminal 19 amino acids of PL-Iv specifically
      recognized PL-Iv, while failing to recognize PL-I. Secreted PL-Iv had an affinity
      for concanavalin A, whereas secreted PL-I lacked affinity for the lectin. PL-I
      was predominantly secreted as a 36-40-kDa species and PL-Iv was predominantly
      secreted as a 33-kDa species. Furthermore, PL-I and PL-Iv were synthesized at
      different times during gestation and by different cell types. PL-I was
      synthesized by trophoblast giant cells during the first half of gestation, while
      PL-Iv was predominantly synthesized by spongiotrophoblast cells during the later
      stages of gestation. PL-Iv was shown to stimulate the proliferation of rat Nb2
      lymphoma cells, an in vitro measure of lactogenic activity. In summary, PL-Iv
      shares structural similarities with PL-I; however, it shows other structural
      differences in addition to unique cell- and temporal-specific patterns of
      expression in the rat chorioallantoic placenta.

PMID- 1988438
TI  - Mutational analysis of the transin (rat stromelysin) autoinhibitor region
      demonstrates a role for residues surrounding the "cysteine switch".
AB  - The family of mammalian extracellular matrix metalloproteases (MMPs) are secreted
      by cells in an inactive (latent) proenzyme form. A highly conserved amino acid
      sequence, PRCGVPDV, is found near the COOH-terminal end of the pro-domain of
      these MMPs and believed to act as an "autoinhibitor." Recent studies (Springman,
      E. B., Angleton, E. L., Birkedal-Hansen, H., and Wart, H. E. V. (1990) Proc.
      Natl. Acad. Sci. U. S. A. 87, 364-368) indicate the Cys of this sequence ligands
      to the active-site zinc keeping the proenzyme in an inactive state, and
      mutational analysis (Sanchez-Lopez, R., Nicholson, R., Gesnel, M. C., Matrisian,
      L. M., and Breathnach, R. (1988) J. Biol. Chem. 263, 11892-11899) suggests that
      the conserved residues surrounding this Cys are required for latency. We have
      constructed 16 new site-directed mutations of the PRCGVPDV autoinhibitor region
      of the MMP transin (rat stromelysin) and tested whether these mutant enzymes are
      produced in a latent or activated form. We find that the conserved Arg as well as
      the Cys are essential for maintaining latency. The Cys cannot be replaced by
      other zinc-liganding amino acids, and the Arg cannot be replaced by Lys. Residues
      immediately surrounding the Cys are sensitive to even conservative amino acid
      substitutions. We show that a synthetic peptide PRCGVPDV is capable of acting as
      a weak inhibitor of transin and that replacement of the Cys with a Ser abolishes
      inhibition by the peptide. A review of the current knowledge of MMP substrate
      specificity in combination with these new results suggests that the PRCGVPDV
      sequence does not inhibit activity by mimicking the known substrates of the
      protease.

PMID- 1988440
TI  - The conformational stability and flexibility of insulin with an additional
      intramolecular cross-link.
AB  - The conformational stability and flexibility of insulin containing a cross-link
      between the alpha-amino group of the A-chain to the epsilon-amino group of Lys29
      of the B-chain was examined. The cross-link varied in length from 2 to 12 carbon
      atoms. The conformational stability was determined by guanidine hydrochloride
      induced equilibrium denaturation and flexibility was assessed by H2O/D2O amide
      exchange. The cross-link has substantial effects on both conformational stability
      and flexibility which depend on its length. In general, the addition of a cross
      link enhances conformational stability and decreases flexibility. The optimal
      length for enhanced stability and decreased flexibility was the 6-carbon link.
      For the 6-carbon link the Gibbs free energy of unfolding was 8.0 kcal/mol
      compared to 4.5 kcal/mol for insulin, and the amide exchange rate decreased by at
      least 3-fold. A very short cross-link (i.e. the 2-carbon link) caused
      conformational strain that was detectable by a lack of stabilization in the Gibbs
      free energy of unfolding and enhancement in the amide exchange rate compared to
      insulin. The effect of the cross-link length on insulin hydrodynamic properties
      is discussed relative to previously obtained receptor binding results.

PMID- 1988441
TI  - Monomer-tetramer equilibrium of the Escherichia coli ssb-1 mutant single strand
      binding protein.
AB  - The Escherichia coli single strand binding (SSB) protein is an essential protein
      required for DNA replication and involved in recombination and a number of repair
      processes. It is a stable homotetramer in solution; however the ssb-1 mutation
      (His-55 to Tyr) destabilizes the tetramer with respect to monomers and this
      defect seems to explain the observed phenotype (Williams, K. R., Murphy, J. B.,
      and Chase, J. W. (1984) J. Biol. Chem. 259, 11804-11811). We report a
      quantitative study of the SSB-1 monomer-tetramer equilibrium in vitro as a
      function of temperature, pH, NaCl, MgCl2, urea, and guanidine hydrochloride
      concentrations. The self-assembly equilibrium was monitored by the increase in
      intrinsic protein fluorescence anisotropy accompanying the formation of the
      tetramer. The experimental isotherms indicate that SSB-1 dimers are not highly
      populated at equilibrium, hence the formation of the tetramer is well-described
      as a one-step association of four monomers. At 25 degrees C, pH 8.1, the monomer
      concentration for 50% tetramer dissociation is (MT)1/2 = 0.87 microM,
      corresponding to a monomer-tetramer equilibrium constant, KT = 3 +/- 1 x 10(18) M
      3. The tetramerization constant, KT, is highly dependent upon temperature and pH,
      with delta H0 = -51 +/- 7 kcal/mol (pH 8.1) and delta H0 = -37 +/- 5 kcal/mol (pH
      6.9). There is no effect of NaCl on the monomer-tetramer association in the range
      from 0.20 to 1.0 M; however, MgCl2 decreases the stability of the SSB-1 tetramer.
      In the presence of high concentrations of the single-stranded oligonucleotide,
      dT(pT)15, the tetramerization constant is slightly increased indicating that
      binding of the oligonucleotide to the SSB-1 monomer promotes the assembly
      process, although not dramatically. The large negative delta H0 that is
      associated with formation of the tetramer provides a likely explanation for the
      temperature sensitivity of the ssb-1 mutation.

PMID- 1988443
TI  - Distinct colchicine binding kinetics of bovine brain tubulin lacking the type III
      isotype of beta-tubulin.
AB  - In mammalian brain, beta-tubulin occurs as a mixture of four isotypes designated
      as types I, II, III, and IV. It has been speculated in recent years that the
      different tubulin isotypes may confer functional diversity to microtubules. In an
      effort to investigate whether different tubulin isotypes differ in their
      functional properties we have studied the colchicine binding kinetics of bovine
      brain tubulin upon removal of the beta III isotype. We found that the removal of
      the beta III isotype alters the binding kinetics from biphasic to monophasic with
      the disappearance of the slow phase. The kinetics become biphasic with the
      reappearance of the slow phase when the beta III-depleted tubulin was mixed with
      the beta III fraction eluted from the affinity column with 0.5 M NaCl. The
      analysis of the kinetic data reveals that the tubulin dimers containing beta III
      bind colchicine at an on-rate constant of 35 M-1 s-1 while those lacking beta III
      bind at 182 M-1 s-1. Our results strongly suggest that the beta-subunit plays a
      very important role in the interaction of tubulin with colchicine.

PMID- 1988442
TI  - Elevated cytosolic Ca2+ activates phospholipase D in human platelets.
AB  - We have examined the activation of phospholipase D in human platelets treated
      with alpha-thrombin. When incubated with 1-O-[9,10-3H2]hexadecyl-2
      lysophosphatidylcholine (PtdCho) and 1-alkyl-[32P]lysoPtdCho for 2 h, platelets
      formed 3H/32P-labeled PtdCho in a ratio of 11:1. After incubation of such labeled
      platelets with alpha-thrombin for 5 min, increased accumulation of 3H/32P-labeled
      phosphatidic acid (PtdOH) was detected in the same ratio, indicating the action
      of phospholipase D. The Ca2+ ionophore A23187 and alpha-thrombin each stimulated
      the formation of labeled PtdOH as above in a time- and concentration-dependent
      manner, with only minor changes in labeled diglyceride. A23187 was able to cause
      increases in labeled PtdOH comparable to those observed with alpha-thrombin. beta
      Phorbol 12,13-dibutyrate, an activator of protein kinase C, only slightly
      stimulated the accumulation of labeled PtOH. The protein kinase C inhibitor,
      staurosporine, totally blocked these changes but only slightly inhibited the
      increases in labeled PtdOH promoted by alpha-thrombin. These results suggest that
      an increase in intracellular Ca2+, rather than protein kinase C activity, is a
      major factor regulating phospholipase D in platelets exposed to alpha-thrombin.
      We have also examined the relative contributions of phospholipase D and
      diglyceride kinase (following phospholipase C action) to PtdOH accumulation in
      [32P]Pi-labeled platelets by comparing the 32P-specific radioactivities of PtdOH,
      PtdCho, and metabolic gamma-ATP in control and alpha-thrombin-exposed platelets.
      Based on these determinations, we conclude that 13 and 87% of incremental PtdOH
      in human platelets exposed to alpha-thrombin arises via phospholipase D acting on
      PtdCho and phospholipase C/diglyceride kinase, respectively.

PMID- 1988444
TI  - Yeast thioredoxin genes.
AB  - Based on the conserved protein sequence of thioredoxins from yeast and other
      organisms, two primers were synthesized for polymerase chain reaction of yeast
      genomic DNA. A 34-base pair (bp) sequence around the active site of yeast
      thioredoxin was obtained from the polymerase chain reaction product. This
      specific sequence was used as a probe in Southern blot analysis of total yeast
      genomic DNA digested with various restriction enzymes. Under conditions of high
      stringency, more than one DNA species hybridized with the probe, suggesting that
      more than one gene encodes yeast genomic library. Two Sau3A1 fragments, 825 and
      2045 bp, respectively, from two different clones were cloned into pUC13. Sequence
      analysis of these fragments gave two different open reading frames without
      introns. The 825-bp Sau3A1 fragment encodes a 103-amino acid residue protein
      named thioredoxin I. The 2045-bp Sau3A1 fragment contains a sequence encoding
      thioredoxin II which has 102 amino acid residues. This is the first report of the
      cloning and sequencing of eukaryotic thioredoxin genes from any source. Both
      yeast thioredoxins contain a dithiol active site sequence, Cys-Gly-Pro-Cys.
      Thioredoxins I and II show 78% amino acid sequence identity. They display more
      amino acid sequence similarity with mammalian thioredoxin than with Escherichia
      coli and plant chloroplast thioredoxins.

PMID- 1988445
TI  - Characterization of novel mRNAs encoding enzymes involved in peptide alpha
      amidation.
AB  - The COOH-terminal alpha-amidation of bioactive peptides is a 2-step process
      catalyzed by two separable enzymatic activities both derived from the
      peptidylglycine alpha-amidating monooxygenase (PAM) precursor. Two forms of PAM
      mRNA (rPAM-1 and -2), differing by the presence or absence of optional Exon A,
      were previously characterized; both encode precursors predicted to have an NH2
      terminal signal sequence, an intragranular domain containing both enzymatic
      activities, and a single transmembrane domain followed by a short, cytoplasmic
      COOH-terminal domain. In this report, two novel types of PAM mRNA were identified
      in adult rat atrium. A cDNA of each type was sequenced, and the results indicate
      that rPAM-3 and -4 could be related to each other and to the previously
      characterized rat PAM cDNAs by alternative mRNA splicing. Deletion of a 258
      nucleotide segment (optional Exon B) encoding the transmembrane domain from rPAM
      3 and the presence of a novel 3'-exon in rPAM-4 mean that both rPAM-3 and -4
      mRNAs encode precursor proteins that have an NH2-terminal signal peptide but lack
      a transmembrane domain. The rPAM-4 precursor protein lacks the region of the PAM
      precursor catalyzing the second step in the alpha-amidation reaction. Low levels
      of rPAM-3 and -4 type mRNA were detected in atrium. Utilizing the polymerase
      chain reaction, two major patterns of distribution of forms of PAM mRNA were
      found. In the heart and central nervous system, PAM mRNAs both containing and
      lacking optional Exon A were prevalent and almost all of the PAM mRNAs detected
      contained optional Exon B. In the pituitary and submaxillary glands, PAM mRNAs
      lacking optimal Exon A were prevalent, as were PAM mRNAs lacking all or part of
      optional Exon B. Since the distribution of PAM activity between soluble and
      membrane fractions is tissue-specific and developmentally regulated and since
      rPAM-4 lacks an enzymatic portion of the PAM precursor, the tissue-specific
      expression of these forms of rat PAM mRNA is expected to be of functional
      significance.

PMID- 1988446
TI  - Modified enterotoxin signal sequences increase secretion level of the recombinant
      human epidermal growth factor in Escherichia coli.
AB  - Amino acid substitutions were made in the heat-labile enterotoxin signal sequence
      of Escherichia coli by recombinant DNA techniques, and their influence on the
      secretion of recombinant human epidermal growth factor by E. coli was examined.
      The heat-labile enterotoxin signal sequence is an amino-terminal extension of the
      octadecapeptide chain and is comprised of three distinct regions: a positively
      charged amino-terminal region, a central hydrophobic region, and a carboxyl
      terminal region with the cleavage site recognized by the signal peptidase. Some
      alterations in the signal sequence caused a 1.5-3.5-fold increase in the
      secretion of recombinant human epidermal growth factor. These were the
      introduction of: (i) polar and small residues into the carboxyl-terminal region
      (replacement of Pro-1 Leu-3 with Asn-Ala or Ser-Ala), which may give a favorable
      structure for the recognition and cleavage by the signal peptidase; and (ii) a
      polar residue into the central hydrophobic region (replacement of Ile-9 with
      Ser), which may cause an increase of the affinity to the cytoplasmic membrane. In
      the latter case, a large amount of the unprocessed "precursor" was accumulated.
      The combination of these modifications, however, did not work additively. An
      increase in the amino-terminal positive charge (insertion of Lys) had no effect
      on secretion. These results prove that the level of protein secretion is greatly
      dependent on the polarity of the carboxyl-terminal region and the hydrophobicity
      and/or the amphiphilicity of the central region. Moreover, the overall balance of
      the physicochemical properties of respective regions is important.

PMID- 1988447
TI  - Antibody-induced dimerization activates the epidermal growth factor receptor
      tyrosine kinase.
AB  - The relationship between epidermal growth factor receptor (EGF-R) protein
      tyrosine kinase activation and ligand-induced receptor dimerization was
      investigated using several bivalent anti-EGF-R antibodies directed against
      various receptor epitopes. In A431 membrane preparations and permeabilized cells,
      all antibodies were able to activate the EGF-R tyrosine kinase, as measured by
      EGF-R autophosphorylation and phosphorylation of other substrates on tyrosine
      residues. EGF-R tyrosine kinase activation correlated strongly with the induction
      of EGF-R dimerization. (i) Both processes specifically occurred in a narrow
      antibody concentration range; (ii) both processes required the presence of
      detergent; and (iii) both processes depended on antibody bivalence since
      monovalent Fab fragments were inactive yet regained full activity after cross
      linking by a second bivalent antibody. These data demonstrate that antibody
      bivalence is essential and sufficient for EGF-R activation and that activation
      occurs regardless of the EGF-R epitope recognized. Finally, EGF-R dimerization
      was shown not to depend on receptor autophosphorylation since it still occurred
      in the absence of ATP. Also, partial inhibition of the tyrosine kinase activity
      by the specific EGF-R tyrosine kinase inhibitor tyrphostin AG 213 did not affect
      formation of EGF-R dimers. Taken together these results demonstrate that
      induction of EGF-R dimerization is sufficient and in case of antibody action,
      essential, for activation of the EGF-R tyrosine kinase and thus provide strong
      support for an intermolecular mechanism of EGF-R tyrosine kinase activation.

PMID- 1988448
TI  - Contributory effects of de novo transcription and premature transcript
      termination in the regulation of human epidermal growth factor receptor proto
      oncogene RNA synthesis.
AB  - Overexpression of the epidermal growth factor (EGF) receptor (c-erbB) proto
      oncogene is a frequent occurrence in human carcinoma and appears to accompany
      autocrine or paracrine transforming growth factor-alpha expression, which in
      model systems can result in activation of EGF receptor tyrosine kinase activity
      and phenotypic transformation. Here we have investigated the transcriptional
      regulation of the EGF receptor gene, by run-on transcription in isolated nuclei
      derived from epithelioid tumor lines. The level of transcription was measured at
      various points on the 100-kilobase pair EGF receptor gene locus, on either sense
      or antisense DNA strands. We find the level of sense strand transcription along
      exon 1 is 8-fold higher than transcription in exons 2-26. Primary EGF receptor
      transcripts appear to pause or terminate prematurely between exons 1 and 2.
      Termination was mapped to a sequenced region approximately 2 kilobase pairs 3' of
      exon 1, proximal to a previously reported DNase I hypersensitive site and an
      enhancer-like activity. Transcription in the CpG-rich region surrounding exon 1
      is bidirectional, with antisense transcripts initiating in intron 1 and extending
      through the coding first exon. Activation of protein kinase C results in a 5-fold
      induction of EGF receptor transcription, accompanied by a slow release in the
      block RNA elongation between exon 2 and exon 26, showing that EGF receptor RNA
      synthesis may be altered by changes in de novo transcription and by a block to
      RNA elongation.

PMID- 1988450
TI  - In vivo pools of free and acylated acyl carrier proteins in spinach. Evidence for
      sites of regulation of fatty acid biosynthesis.
AB  - In order to examine potential regulatory steps in plant fatty acid biosynthesis,
      we have developed procedures for the analysis of the major acyl-acyl carrier
      protein (ACP) intermediates of this pathway. These techniques have been used to
      separate and identify acyl-ACPs with chain configurations ranging from 2:0 to
      18:1 and to determine the relative in vivo concentrations of acyl-ACPs in spinach
      leaf and developing seed. In both leaf and seed as much as 60% of the total ACPs
      were nonesterified (free), with the remaining proportion consisting of acyl-ACP
      intermediates leading to the formation of palmitate, stearate, and oleate. In
      spinach leaf the proportions of the various acyl groups esterified to each ACP
      isoform were indistinguishable, indicating that these isoforms are utilized
      similarly in de novo fatty acid biosynthesis in vivo. However, the acyl group
      distribution pattern of seed ACP-II differed significantly from that of leaf ACP
      II. The malonyl-ACP levels were less than the 4:0-ACP and 6:0-ACP levels in leaf,
      and in contrast, the malonyl-ACP-II levels in seed were approximately 3-fold
      higher than the 4:0-ACP-II and 6:0-ACP-II levels. In addition, the ratio of
      oleoyl-ACP-II (18:1) to stearoyl-ACP-II (18:0) was higher in seed than in leaf.
      These data suggest that the differences in acyl-ACP patterns reflect a
      tissue/organ-specific difference rather than an isoform-specific difference. In
      extracts prepared from leaf samples collected in the dark, the levels of acetyl
      ACPs were approximately 5-fold higher compared to samples collected in the light.
      The levels of free ACPs showed an inverse response, increasing in the light and
      decreasing in the dark. Notably there was no concomitant increase in the malonyl
      ACP levels. The most likely explanation for the major increase in acetyl-ACP
      levels in the dark is that light/dark control over the rate of fatty acid
      biosynthesis occurs at the reaction catalyzed by acetyl-CoA carboxylase.

PMID- 1988449
TI  - Stimulation of the processivity of the DNA polymerase of bacteriophage T4 by the
      polymerase accessory proteins. The role of ATP hydrolysis.
AB  - In this paper we examine the role of the DNA polymerase accessory proteins in
      modulating the processivity of DNA synthesis by the bacteriophage T4-coded five
      protein "holoenzyme" replication complex in vitro. Primed single-stranded DNA was
      used as a template for the DNA synthesis reactions, and buffer conditions were
      chosen to mimic in vivo salt concentrations. We find that the accessory proteins
      significantly increase the DNA-bound lifetime of the holoenzyme complex but that
      the maximum lifetime of the complex is still less than 10 s at 22 degrees C. The
      accessory proteins greatly enhance the processivity of the holoenzyme relative to
      that of the polymerase alone. ATP hydrolysis catalyzed by the accessory proteins
      complex is required to achieve this enhancement. We have investigated the
      temporal relationship between ATP hydrolysis by the accessory proteins and primer
      elongation by the holoenzyme and find that ATPase activity is required for
      initial assembly of the holoenzyme complex but not for elongation per se. Thus we
      conclude that the increased processivity displayed by the holoenzyme in moving
      through regions of template secondary structure reflects the high intrinsic
      processivity of the holoenzyme complex itself rather than a requirement for a
      concomitant ATPase-driven helicase activity during elongation. We have also
      measured the ATPase activity of the accessory proteins as a function of
      polymerase concentration and find that the rate of ATP hydrolysis catalyzed by
      this complex decreases significantly when the accessory proteins are assembled
      (with polymerase and gene 32 protein) into the five-protein holoenzyme and
      coupled to primer elongation. Based on these results we discuss mechanisms by
      which the ATPase activity of the polymerase accessory proteins might stimulate
      the overall processivity of the holoenzyme.

PMID- 1988451
TI  - Role of a disulfide bond in the thermal stability of the LamB protein trimer in
      Escherichia coli outer membrane.
AB  - In order to understand the unusual heat resistance of LamB protein (the outer
      membrane component of the maltose transport system in Escherichia coli and its
      receptor for bacteriophage lambda), we investigated the role of its 2 cysteinyl
      residues. Our studies show that Cys22 and Cys38 form an intrasubunit disulfide
      bond which contributes to the heat stability of the LamB protein trimer. Physical
      evidence for the disulfide was obtained by using site-directed mutagenesis to
      convert Asn36 to Met, which allowed cyanogen bromide cleavage between the 2
      cysteines. Upon reduction one of the N36M fragments migrated as two pieces,
      resolved by two-dimensional polyacrylamide gel electrophoresis. Other mutagenized
      LamB proteins, in which 1 or both Cys residues were converted to Ser, exhibited a
      sharp loss of thermal stability. In contrast to wild-type LamB protein trimer,
      which does not dissociate to monomers even after 60 min at 100 degrees C, only 10
      15% of the mutant LamB proteins remain trimeric after boiling 10 min. The
      disulfide bond in LamB protein is not required for its transport function, since
      both mutagenized LamB protein and N-ethylmaleimide-labeled LamB protein exhibit
      normal uptake of sugars in proteoliposomes. Finally, the disulfide bond must not
      be between subunits of the LamB trimer since reversible dissociation of trimer is
      achieved by low pH or denaturants in the absence of reducing agent.

PMID- 1988452
TI  - A de novo G to T transversion in a pro-alpha 1 (I) collagen gene for a moderate
      case of osteogenesis imperfecta. Substitution of cysteine for glycine 178 in the
      triple helical domain.
AB  - Cultured fibroblasts from a patient affected with a moderate form of osteogenesis
      imperfecta were defective for the synthesis of type I collagen molecules; about
      half of the alpha 1(I) chains contained a cysteine residue in the triple helical
      domain and a disulfide link formed when two mutant alpha 1(I) chains were
      incorporated into a type I collagen heterotrimer. The proband's parents were
      clinically and biochemically normal. The cysteine was localized within peptide
      alpha 1(I)CB8 between residues 170 and 200 of the triple helical domain using a
      chemical procedure with 2-nitro-5-thiocyanobenzoic acid (Tenni, R., Rossi, A.,
      Valli, M., Mottes, M., Pignatti, P. F., and Cetta, G. (1990) Matrix 10, 20-26).
      Type I procollagen heterotrimers containing either one or two mutant chains
      showed (i) a slight abnormality in secretion from cells; (ii) a low degree of
      post-translational overmodifications; (iii) the same, but lower than normal,
      thermal stability. Total RNA was isolated from the proband's dermal fibroblast
      cultures, and cDNAs for pro-alpha 1(I) were prepared d using total RNA. A portion
      of cDNA, coding for the region encompassing residues 119-193 of alpha 1(I) triple
      helical domain, was amplified by polymerase chain reaction. A single base pair
      mismatch was identified by chemical cleavage of DNA.DNA heteroduplexes,
      indicating a possible substitution of a guanine in the triplet coding for glycine
      178 or 181. The same unique mismatch was detected by chemical cleavage in about
      one-half of the molecules in heteroduplexes formed between patient's pro-alpha
      1(I) mRNAs and a normal cDNA probe. The amplified products were cloned and
      sequenced, confirming the heterozygous nature of the patient and demonstrating
      the presence and the location of a missense mutation; a single T for G
      substitution was found in the first base of the triplet coding for residue 178 of
      alpha 1(I) triple helical domain, leading to a cysteine for glycine substitution.
      Allele-specific oligonucleotide hybridization to amplified DNA confirmed a de
      novo point mutation in the proband's genome. The findings in this patient are in
      accord with the phenotypic gradient model, which correlates the localization of
      the structural defect with the clinical outcome of osteogenesis imperfecta. The
      mutant protein has some properties that differ from the caused by the cysteine
      for glycine 175 substitution, suggesting a direct influence of the neighboring
      amino acids on the effects of the mutation.

PMID- 1988453
TI  - Induction of calbindin-D 9k mRNA but not calcium transport in rat intestine by
      1,25-dihydroxyvitamin D3 24-homologs.
AB  - The function and precise mechanism of regulation of calbindin-D 9k in intestine
      is largely unknown. It is suggested that this calcium binding protein is involved
      in active intestinal calcium transport and that its expression is mainly mediated
      by 1,25-dihydroxyvitamin D3. We examined the effect of two side chain modified
      analogs of 1,25-dihydroxyvitamin D3 as compared to 1,25-dihydroxyvitamin D3
      itself on the regulation of the calbindin-D 9k at the mRNA level and on
      intestinal calcium transport in the rat. delta 22-24,24-dihomo-1,25
      dihydroxyvitamin D3 at a single dose of 500, 1,000, and 2,000 pmol caused greater
      than 7.0-fold increase in calbindin-D 9k mRNA without stimulating intestinal
      calcium transport. A 10,000-pmol dose of delta 22-24,24,24-trihomo-1,25
      dihydroxyvitamin D3 caused a 7.6-fold increase in calbindin-D 9k mRNA without
      significantly increasing intestinal absorption of calcium. In contrast, 1,25
      dihydroxyvitamin D3 caused a parallel increase in calbindin-D 9k mRNA and
      intestinal absorption of calcium. Thus, calbindin 9k is not by itself responsible
      for 1,25-dihydroxyvitamin D3-mediated increase in intestinal absorption of
      calcium.

PMID- 1988454
TI  - Activation of messenger-independent protein kinases in wild-type and phorbol
      ester-resistant EL4 thymoma cells.
AB  - Phorbol esters, acting via activation of the protein kinase C family of protein
      serine/threonine kinases, are able to exert profound effects on various cellular
      functions. In this study, we used the EL4 thymoma cell line to study the
      potential role of "downstream" protein serine/threonine kinases in cellular
      responses to phorbol esters. In wild-type EL4 cells, addition of phorbol ester
      caused a rapid activation of kinase activity toward RRLSSLRA (S6P). This
      increased activity was maintained for at least 15 min but diminished to control
      levels by 60 min. Activation of a myelin basic protein (MBP) kinase was also seen
      in response to phorbol ester. In a variant EL4 cell line in which phorbol ester
      does not induce interleukin 2 transcription, phorbol ester failed to activate
      either the S6P kinase or MBP kinase. Partial purification of the activated S6P
      and MBP kinases from wild-type cells showed that they represent separate enzymes
      that are distinct from protein kinase C. Although the variant cells had reduced
      levels of protein kinase C as compared with the wild-type cells, the amount of
      membrane-bound enzyme increased in response to phorbol 12-myristate 13-acetate in
      both wild-type and variant cells. Treatment of intact cells with phorbol ester
      resulted in phosphorylation of some of the same protein substrates in both cell
      lines. Okadaic acid, a phosphatase inhibitor, increased S6P and MBP kinase
      activities in both wild-type and variant cells. Thus, phorbol ester failed to
      activate the S6P and MBP kinases in the variant cells even though these cells
      express activatable protein kinase C, S6P kinase, and MBP kinase. Two protein
      kinase inhibitors, staurosporine and H-7, inhibited the activity of all three
      kinases in vitro, while a peptide inhibitor (PKC 19-31) showed specificity for
      protein kinase C. In summary, these results suggest that activation of messenger
      independent protein kinases may be critical for certain protein kinase C
      dependent responses.

PMID- 1988455
TI  - Cloning of the cDNA and gene for mouse mast cell protease 4. Demonstration of its
      late transcription in mast cell subclasses and analysis of its homology to
      subclass-specific neutral proteases of the mouse and rat.
AB  - Based on the amino-terminal amino acid sequence of the mature form of mouse mast
      cell protease 4 (MMCP-4), previously identified in peritoneal connective tissue
      mast cells (CTMC) and Kirsten sarcoma virus-immortalized mast cells (KiSV-MC), a
      26-mer oligonucleotide probe was constructed and used to clone cDNAs for MMCP-4
      from a KiSV-MC1 cDNA library. MMCP-4 is the first secretory granule serine
      protease of CTMC to be molecularly cloned. Using a cDNA probe derived from the 3'
      untranslated portion of the MMCP-4 cDNA, the gene for MMCP-4 and a second highly
      related gene (mouse mast cell protease-like, MMCP-L) were cloned from a BALB/c
      mouse genomic DNA library and sequenced entirely, including approximately 2
      kilobases of the 5'-flanking region. MMCP-4 and MMCP-L have five exons of
      identical length, four introns of nearly identical length, and approximately 900
      base pairs of 5'-flanking DNA with sequence similarity by dot matrix analysis. By
      RNA blot analysis with gene-specific probes for MMCP-4 (bases 497-633 of the
      cDNA) and MMCP-L (bases 502-638 of the cDNA), mRNA for MMCP-4 was present in KiSV
      MC5, CTMC, and the intestine of a mouse infected with the parasite
      Nippostrongylus brasiliensis markedly enriched for mucosal mast cells (MMC); MMCP
      L mRNA was detected only in the intestine of the N. brasiliensis-infected mouse.
      MMCP-4 mRNA was not expressed in normal mouse intestine or in interleukin 3
      dependent bone marrow-derived mast cells, which can serve as precursors to both
      MMC and CTMC. This finding suggests that MMCP-4 is transcribed relatively late in
      the development of both the CTMC and MMC subclasses and underscores the fact that
      mouse bone-marrow-derived mast cells are immature mast cells, rather than tissue
      culture equivalents of the MMC subclass.

PMID- 1988456
TI  - A maturase-like subunit of the sequence-specific endonuclease endo.SceI from
      yeast mitochondria.
AB  - Some yeast strains possess a sequence-specific endonuclease, Endo.SceI, which is
      a heterodimeric enzyme localized in mitochondria. The larger subunit (75 kDa) of
      Endo.SceI, encoded by a nuclear gene (ENS1), is transported from the cytosol into
      the mitochondria. In this study, we determined the partial amino acid sequence of
      the smaller subunit (50 kDa) of Endo.SceI. The determined sequence matched well
      the partial sequence deduced from a mitochondrial open reading frame (RF3). The
      RF3 locus is known to exhibit polymorphism since this reading frame in some yeast
      strains is supposed to encode a maturase-like protein, whereas in other strains,
      the frame is interrupted by GC clusters, which thus break the frame. Southern
      blot analysis of various yeast strains showed that the continuity of RF3 is
      correlated with the presence of Endo.SceI activity. These data indicate that the
      continuous RF3 sequence is a functional gene (ENS2) coding for the smaller
      subunit of Endo.SceI. The results of cytoduction, by which the continuous RF3
      sequence was transferred into a yeast strain lacking mitochondrial DNA, confirmed
      this conclusion. This study suggests the involvement of Endo.SceI in genetic
      recombination of mitochondrial DNA.

PMID- 1988457
TI  - The chromatin structure of centromeres from fission yeast: differentiation of the
      central core that correlates with function.
AB  - We have examined the chromatin structure of centromere regions from the fission
      yeast Schizosaccharomyces pombe. The large and complex centromere regions of the
      S. pombe chromosomes encompass many kilobase pairs of DNA and contain several
      classes of tandemly repeated DNA sequences. The repeated sequences are further
      organized into a large inverted repeat flanking a central core, a conserved
      structural feature among all three centromeres in S. pombe. The nucleosomal
      configuration of the centromere regions is nonuniform and highly varied. Most of
      the centromere-specific repeated DNA sequences are packaged into nucleosomes
      typical of bulk chromatin. However, the central core and core-associated repeated
      sequences from the centromere regions of chromosomes I (cen1) and II (cen2), when
      present in S. pombe, show an altered chromatin structure, with little or no
      evidence of regular nucleosomal packaging. The atypical chromatin organization of
      the cen2 central core is not due to transcription, as no transcripts from this
      region were detected. These same DNA sequences, however, are packaged into
      nucleosomes typical of bulk chromatin when present in a nonfunctional environment
      on a minichromosome in the budding yeast Saccharomyces cerevisiae. Because the
      cen2 central core sequences themselves do not preclude regular nucleosomal
      packaging, we speculate that in S. pombe they constitute a specialized site of
      kinetochore protein assembly. The atypical nucleosomal pattern of the cen2
      central core remains constant during the cell cycle, with only minor differences
      observed for some sequences. We propose that the unusual chromatin organization
      of the core region forms the basis of a higher order structural differentiation
      that distinguishes the centromere from the chromosome arms and specifies the
      essential structure for centromere function.

PMID- 1988458
TI  - Vaults. III. Vault ribonucleoprotein particles open into flower-like structures
      with octagonal symmetry.
AB  - The structure of rat liver vault ribonucleoprotein particles was examined using
      several different staining techniques in conjunction with EM and digestion with
      hydrolytic enzymes. Quantitative scanning transmission EM demonstrates that each
      vault particle has a total mass of 12.9 +/- 1 MD and contains two centers of
      mass, suggesting that each vault particle is a dimer. Freeze-etch reveals that
      each vault opens into delicate flower-like structures, in which eight rectangular
      petals are joined to a central ring, each by a thin hook. Vaults examined by
      negative stain and conventional transmission EM (CTEM) also reveal the flower
      like structure. Trypsin treatment of vaults resulted exclusively in cleavage of
      the major vault protein (p104) and concurrently alters their structure as
      revealed by negative stain/CTEM, consistent with a localization of p104 to the
      flower petals. We propose a structural model that predicts the stoichiometry of
      vault proteins and RNA, defines vault dimer-monomer interactions, and describes
      two possible modes for unfolding of vaults into flowers. These highly dynamic
      structural variations are likely to play a role in vault function.

PMID- 1988459
TI  - 42Sp48 in previtellogenic Xenopus oocytes is structurally homologous to EF-1
      alpha and may be a stage-specific elongation factor.
AB  - We have isolated the cDNA for 42Sp48 and EF-1 alpha from mixed stage oocytes and
      tailbud (stage 22) Xenopus laevis cDNA libraries by use of the cDNA for human
      elongation factor-1 alpha (EF-1 alpha) as probe. The nucleotide and deduced amino
      acid sequences of the entire coding region of 42Sp48 and EF-1 alpha cDNA were
      established. The proposed functional homology of the proteins is reflected in
      highly conserved amino acid sequences (91% identity), while the large number of
      silent mutations at the gene level may serve to prevent recombination at their
      loci. 42Sp48 is apparently encoded by two genes in Xenopus, while no sequences
      corresponding to 42Sp48 could be found in murine or human genomic DNA. 42Sp48 has
      been proposed to act as a stage-specific elongation factor in Xenopus. Comparison
      of the deduced amino acid sequences of 42Sp48 and EF-1 alpha with that of
      elongation factor Tu from E. coli, for which the three-dimensional structure
      including that of the GTP binding sites have been determined, supports this
      hypothesis.

PMID- 1988460
TI  - Formation and intracellular transport of a heterodimeric viral spike protein
      complex.
AB  - We have analyzed the heterodimerization and intracellular transport from the ER
      to the Golgi complex (GC) of two membrane glycoproteins of a bunyavirus
      (Uukuniemi virus) that matures by a budding process in the GC. The glycoproteins
      G1 and G2, which form the viral spikes, are cotranslationally cleaved in the ER
      from a 110,000-D precursor. Newly synthesized G1 was transported to the GC and
      incorporated into virus particles about 30-45 min faster than newly synthesized
      G2. Analysis of the kinetics of intrachain disulfide bond formation showed that
      G1 acquired its mature form within 10 min, while completion of disulfide bond
      formation of G2 required a considerably longer time (up to 60 min). During the
      maturation process, G2 was transiently associated with the IgG heavy chain
      binding protein for a longer time than G1. Protein disulfide isomerase also
      coprecipitated with antibodies against G1 and G2. In virus particles, G1 and G2
      were present exclusively as heterodimers. Immunoprecipitation with monoclonal
      antibodies showed that heterodimerization occurred rapidly, probably in the ER,
      between newly made G1 and mature, dimerization competent G2. Taken together, our
      results show that these two viral glycoproteins have different maturation
      kinetics in the ER. We conclude that the apparent different kinetics of ER to GC
      transport of G1 and G2 is due to the different rates by which these proteins fold
      and become competent to enter into heterodimeric complexes prior to exit from the
      ER.

PMID- 1988461
TI  - Lipid traffic between high density lipoproteins and Plasmodium falciparum
      infected red blood cells.
AB  - Several intraerythrocytic growth cycles of Plasmodium falciparum could be
      achieved in vitro using a serum free medium supplemented only with a human high
      density lipoprotein (HDL) fraction (d = 1.063-1.210). The parasitemia obtained
      was similar to that in standard culture medium containing human serum. The
      parasite development was incomplete with the low density lipoprotein (LDL)
      fraction and did not occur with the VLDL fraction. The lipid traffic from HDL to
      the infected erythrocytes was demonstrated by pulse labeling experiments using
      HDL loaded with either fluorescent NBD-phosphatidylcholine (NBD-PC) or
      radioactive [3H]palmitoyl-PC. At 37 degrees C, the lipid probes rapidly
      accumulated in the infected cells. After incubation in HDL medium containing
      labeled PC, a subsequent incubation in medium with either an excess of native HDL
      or 20% human serum induced the disappearance of the label from the erythrocyte
      plasma membrane but not from the intraerythrocytic parasite. Internalization of
      lipids did not occur at 4 degrees C. The mechanism involved a unidirectional flux
      of lipids but no endocytosis. The absence of labeling of P. falciparum, with HDL
      previously [125I]iodinated on their apolipoproteins or with antibodies against
      the apolipoproteins AI and AII by immunofluorescence and immunoblotting,
      confirmed that no endocytosis of the HDL was involved. A possible pathway of
      lipid transport could be a membrane flux since fluorescence videomicroscopy
      showed numerous organelles labeled with NBD-PC moving between the erythrocyte and
      the parasitophorous membranes. TLC analysis showed that a partial conversion of
      the PC to phosphatidylethanolamine was observed in P. falciparum-infected red
      cells after pulse with [3H]palmitoyl-PC-HDL. The intensity of the lipid traffic
      was stage dependent with a maximum at the trophozoite and young schizont stages
      (38th h of the erythrocyte life cycle). We conclude that the HDL fraction appears
      to be a major lipid source for Plasmodium growth.

PMID- 1988462
TI  - Extracellular ATP as a trigger for apoptosis or programmed cell death.
AB  - Extracellular ATP is shown here to induce programmed cell death (or apoptosis) in
      thymocytes and certain tumor cell lines. EM studies indicate that the ATP-induced
      death of thymocytes and susceptible tumor cells follows morphological changes
      usually associated with glucocorticoid-induced apoptosis of thymocytes. These
      changes include condensation of chromatin, blebbing of the cell surface, and
      breakdown of the nucleus. Cytotoxicity assays using double-labeled cells show
      that ATP-mediated cell lysis is accompanied by fragmentation of the target cell
      DNA. DNA fragmentation can be set off by ATP but not the nonhydrolysable analogue
      ATP gamma S nor other nucleoside-5'-triphosphates. ATP-induced DNA fragmentation
      but not ATP-induced 51Cr release can be blocked in cells pretreated with
      inhibitors of protein or RNA synthesis or the endonuclease inhibitor, zinc;
      whereas pretreatment with calmidazolium, a potent calmodulin antagonist, blocks
      both DNA fragmentation and 51Cr release. The biochemical and morphological
      changes caused by ATP are preceded by a rapid increase in the cytoplasmic calcium
      of the susceptible cell. Calcium fluxes by themselves, however, are not
      sufficient to cause apoptosis, as the pore-forming protein, perforin, causes cell
      lysis without DNA fragmentation or the morphological changes associated with
      apoptosis. Taken together, these results indicate that ATP can cause cell death
      through two independent mechanisms, one of which, requiring an active
      participation on the part of the cell, takes place through apoptosis.

PMID- 1988463
TI  - Purification and characterization of an 82-kD membrane protein as a neurite
      outgrowth factor binding protein: possible involvement of NOF binding protein in
      axonal outgrowth in developing retina.
AB  - Neurite outgrowth factor (NOF) is a glycoprotein isolated from an extract of
      gizzard that induces neurite outgrowth from cultured retinal or ciliary
      ganglionic (CG) neurons. We have reported that a glycoprotein of approximately 82
      kD solubilized from gizzard muscles binds to NOF (ligand blotting) and inhibits
      the neurite promoting activity of NOF (inhibition assay). The 82-kD protein (NOF
      binding protein) was purified from gizzard muscle membranes as a doublet band on
      SDS-PAGE and a polyclonal antibody was raised against it. An NOF binding protein
      in developing retina exhibited the same physicochemical properties as that of the
      gizzard muscle. Quantitative decrease in NOF binding protein in embryonic retinas
      was observed after day 11 by the inhibition assay, ligand blotting, and
      immunoblotting, its decrease being parallel with reduction of NOF-induced neurite
      outgrowth of embryonic retinas. In an immunohistochemical study, the antibody
      stained only the optic fiber layers of the retinas of 8-d embryos, and this
      staining was no longer detectable in retinas of 18-d embryos. These results
      suggest that the 82-kD protein is a novel membrane protein that behaves as an NOF
      receptor and that the loss of neuritic response of the retinal neurons to NOF
      reflects a decrease in NOF receptor molecules.

PMID- 1988464
TI  - Microglial mitogens are produced in the developing and injured mammalian brain.
AB  - The central nervous system produces growth factors that stimulate proliferation
      of ameboid microglia during embryogenesis and after traumatic injury. Two
      microglial mitogens (MMs) are recovered from the brain of newborn rat. MM1 has an
      approximate molecular mass of 50 kD and a pI of approximately 6.8; MM2 has a
      molecular mass of 22 kD and a pI of approximately 5.2. These trypsin-sensitive
      proteins show specificity of action upon glia in vitro serving as growth factors
      for ameboid microglia but not astroglia or oligodendroglia. Although the MMs did
      not stimulate proliferation of blood monocytes or resident peritoneal macrophage,
      MM1 shows granulocyte macrophage colony-stimulating activity when tested upon
      bone marrow progenitor cells. Microglial mitogens may help to control brain
      mononuclear phagocytes in vivo. The MMs first appear in the cerebral cortex of
      rat during early development with peak levels around embryonic day E-20, a period
      of microglial proliferation. Microglial mitogens are also produced by traumatized
      brain of adult rats within 2 d after injury. When infused into the cerebral
      cortex, MM1 and MM2 elicit large numbers of mononuclear phagocytes at the site of
      injection. In vitro study shows that astroglia from newborn brain secrete MM2.
      These observations point to the existence of a regulatory system whereby
      secretion of proteins from brain glia helps to control neighboring inflammatory
      responses.

PMID- 1988465
TI  - An Arg-Gly-Asp sequence within thrombin promotes endothelial cell adhesion.
AB  - Thrombin, in addition to its central role in hemostasis, possesses diverse
      cellular bioregulatory functions implicated in wound healing, inflammation, and
      atherosclerosis. In the present study we demonstrate that thrombin molecules
      modified either at the procoagulant or catalytic sites induce endothelial cell
      (EC) adhesion, spreading, and cytoskeletal reorganization. The most potent
      adhesive thrombin analogue (NO2-alpha-thrombin) was obtained by nitration of
      tyrosine residues. The cell adhesion promoting activity of NO2-alpha-thrombin was
      blocked upon the formation of thrombin-antithrombin III (ATIII) complexes and by
      antiprothrombin antibodies, but was unaffected by hirudin. Arg-Gly-Asp-containing
      peptides, fully inhibited EC adhesion to NO2-alpha-thrombin, while synthetic
      peptides corresponding to thrombin "Loop B" mitogenic site and the thrombin
      derived chemotactic fragment "CB67-129", were uneffective. Immunofluorescence
      studies indicated that EC adhesion to NO2-alpha-thrombin was followed by cell
      spreading, actin microfilament assembly, and formation of focal contacts. By the
      use of specific antibodies, the vitronectin (vn) receptor (alpha v beta 3) was
      found to be localized in clusters upon cell adhesion to NO2-alpha-thrombin. An
      anti alpha v beta 3 antibody blocked EC adhesion and spreading while
      antifibronectin (fn) receptor (alpha 5 beta 1) antibodies were uneffective. While
      native thrombin exhibited a very low cell attachment activity, thrombin that was
      incubated at 37 degrees C before coating of plastic surfaces induced EC
      attachment and spreading. We propose that under certain conditions the naturally
      hindered RGD domain within thrombin is exposed for interaction with alpha v beta
      3 on EC. This in turn promotes cell adhesion, spreading, and reorganization of
      cytoskeletal elements, which may altogether contribute to repair mechanisms in
      the disturbed vessel wall. This study defines a new biological role of thrombin
      and characterizes a new recognition mechanism on EC for this molecule.

PMID- 1988466
TI  - Ultrasonography of the unossified patella in young children.
AB  - Ultrasonography has become a useful technique to assess the cartilaginous hip of
      the newborn. We applied this technique and found that it gave useful information
      in helping to locate the unossified patella in two cases of congenital
      dislocation of the patella.

PMID- 1988467
TI  - Pediatric atlantoaxial instability presenting as cerebral and cerebellar
      infarcts.
AB  - Atlantoaxial instability can lead to severe, permanent neurologic compromise and
      death if not treated by cervical fusion. However, identification of atlantoaxial
      subluxation can be difficult owing to the often confusing signs and symptoms. We
      describe a patient with unexplained transient repeated cerebral and cerebellar
      signs who had 10 mm of translation of the atlas on the axis owing to os
      odontoideum with infarcts in the cerebellum and occipital parietal lobes. These
      correlated with angiographically documented vertebral artery narrowing at the
      level of the axis and the subsequent low flow to the posterior cerebellum. After
      stabilization and fusion of the cervical spine, the patient regained normal
      neurologic function and has remained symptom-free at 2 years of follow-up.

PMID- 1988468
TI  - 3-S prosthesis: a preliminary report.
AB  - We report a new prosthetic suspension system ideally suited for active young
      amputees. The silicone suction socket (3-S) utilizes a silicone sleeve that
      intimately fits the residual limb, providing a suction-type suspension for both
      upper and lower extremities. Seven juvenile amputees were evaluated. Six were
      successful and one was deemed a failure. Details of the design concepts,
      fabrication, and method of donning the prosthesis are described. We believe that
      the 3-S design is a significant improvement over conventional prosthetic
      suspension, offering important advantages to the active pediatric amputee.

PMID- 1988469
TI  - Technique of corrective osteotomy through the distal radial metaphysis for the
      restoration of length and position of the epiphysis after physeal injury.

PMID- 1988470
TI  - Assessment of complex hip deformity using three-dimensional CT image.
AB  - We used three-dimensional computed tomography (CT) to define the bony
      configuration of the acetabulum and the proximal femur and their relationship to
      complicated and/or neglected congenital hip dislocations and Legg-Calve-Perthes
      disease. Three-dimensional CT was useful for preoperative planning and
      postoperative evaluation of hips with complex deformities, which were often
      difficult to assess by means of plain radiographs or conventional two-dimensional
      CT. The coverage of the femoral head under the acetabular roof and the severity
      of the hip dysplasia could be assessed easily with three dimensional CT, and
      acetabular and femoral torsion could be measured.

PMID- 1988471
TI  - Physeal remodeling after internal fixation of slipped capital femoral epiphyses.
AB  - Rounding off the femoral neck metaphysis helps improve hip function in slipped
      capital femoral epiphysis (SCFE). Remodeling by physeal growth, not previously
      reported, may also contribute. By studing the changes in physeal-shaft angle
      after internal fixation (IF), we found evidence of physeal remodeling in one of
      21 mild, five of 23 moderate, and in all of 11 severe slips. Although the amount
      of remodeling averaged 11.7 degrees, it occurred in 100% of severe slips (p less
      than 0.001). This support the use of initial pin fixation and a wait of at least
      2 years before realignment femoral neck osteotomies are considered.

PMID- 1988472
TI  - Pitfalls in treatment of Legg-Calve-Perthes disease using proximal femoral varus
      osteotomy.
AB  - A femoral varus osteotomy can be used to contain the femoral head in Legg-Calve
      Perthes (LCP) disease if certain pitfalls can be avoided. We reviewed 74 patients
      who underwent 79 femoral varus osteotomies. The study addressed the pitfalls that
      should be avoided with this technique. It was concluded that the amount of varus
      angulation should barely position the femoral head beneath the lateral rim of the
      acetabulum, avoiding varus less than 105 degrees, and that consideration should
      be given to performing a greater trochanteric epiphysiodesis at the time of
      initial femoral osteotomy. The short-term results reflect a positive attitude
      toward femoral varus osteotomy in treatment of LCP if these pitfalls can be
      avoided.

PMID- 1988474
TI  - Neonatal fractures in myelomeningocele patients.
AB  - Neonatal fractures in all neonatal patients entering a spina bifida clinic over a
      4-year period were reviewed retrospectively. Of six patients with fractures, all
      had thoracic or upper lumbar neurologic levels and all had significant
      contractures. The risk of fracture for patients with these two characteristics
      was 17%. Awareness of the risk of neonatal fracture and care in the handling of
      these children is stressed.

PMID- 1988473
TI  - Glove perforation in pediatric orthopaedic surgery.
AB  - Three hundred eighty-three pairs of gloves were tested for punctures after 100
      consecutive pediatric orthopaedic operations to assess the rate, site, procedure,
      and maneuver during which glove puncture accidents took place. Evidence of
      perforation was found in 14% of the gloves used. Surgeons appear to be
      significantly more at risk for glove perforation than do other members of the
      operating team.

PMID- 1988475
TI  - Aortic anatomy in children with myelomeningocele and congenital lumbar kyphosis.
AB  - Preoperative aortograms were reviewed in six children with thoracic
      myelomeningocele and lumbar kyphosis at an average age of 25 months. In all
      children, the abdominal aorta bridged the lumbar kyphosis. In four children, the
      upper renal poles were close to the spine and were at potential risk during
      kyphectomy. All children had aortic shortening with an increased variability in
      origin of the major abdominal aortic branches. Abnormal lumbar arteries were
      noted in four children.

PMID- 1988476
TI  - Intraspinal abnormalities and congenital spine deformities: a radiographic and
      MRI study.
AB  - Forty-two patients with congenital spinal deformity were studied by magnetic
      resonance imaging (MRI). Sixteen patients had intraspinal abnormalities
      consisting of a tethered cord in 10, diastematomyelia in four, diplomyelia in
      three, syringomyelia in four, a low lying conus in three, and a teratoma of the
      sacrum in one patient. In seven patients, intraspinal anomalies were suspected
      based on routine spinal radiographs and physical findings. We recommend MRI in
      patients undergoing spinal stabilization procedures and in all patients with
      lumbosacral kyphosis and those with pain, neurologic findings, or cutaneous hairy
      patch.

PMID- 1988477
TI  - Natural history of scoliosis in congenital heart disease.
AB  - We defined the natural history of scoliosis in congenital heart disease (CHD)
      with respect to the risk of progression and indications for treatment. We
      reviewed radiographs of 48 children with CHD and scoliosis. Thirty-seven had
      developmental scoliosis (77%), and 11 (23%) had congenital scoliosis. Children
      with congenital scoliosis can be managed in the same way as children without CHD.
      Developmental curves less than 30 degrees in children aged greater than 10 years
      showed no progression. Developmental curves greater than 30 degrees with onset in
      children aged less than 10 years and progression greater than 9 degrees per year
      require treatment.

PMID- 1988478
TI  - Femoral neck and lumbar spine bone mineral densities in a normal population 3-20
      years of age.
AB  - Dual-photon absorptiometry (DPA) with a 153gadolinium radionuclide source was
      used to measure bone mineral in the lumbar spine of 109 subjects and the femoral
      neck of 100 subjects 3-20 years of age. From the scan data collected, multiple
      linear regression models were developed to predict the measured bone mineral
      density values as a function of age, height, and weight; male and female data
      were evaluated separately. From the table of predicted values, a particular
      subject's bone mineral measurements can be readily compared with that of normal
      subjects in the same way "growth charts" are commonly used to assess development.

PMID- 1988479
TI  - Microgeodic disease affecting the hands and feet of children.
AB  - Twenty cases of microgeodic disease affecting the hands or feet of children are
      presented, and the relevant literature is reviewed. Clinical features include
      chilblain-like appearance and tenderness of the involved digits. Radiographically
      patchy osteoporosis of the diaphysis and/or sclerosis of the diaphysis and
      rarefaction of the metaphysis with cortical erosion is evident, often accompanied
      by subperiosteal new bone formation. Characteristically, this condition occurs in
      winter and resolves spontaneously within 6 months clinically and
      radiographically. This lesion appears to result from vascular insufficiency of
      the hands and feet causing bone infarction secondary to intense vasospasm
      precipitated by cold.

PMID- 1988480
TI  - Slipped capital femoral epiphysis: comparison of a roentgenographic method and
      computed tomography in determining slip severity.
AB  - Various conventional roentgenographic methods have been proposed to determine the
      severity of chronic slipped capital femoral epiphysis (SCFE) on the sagittal
      plane, with some maintaining that computed tomography (CT) is more accurate and
      reproduces better than roentgenography. We used a modified Dunlap's technique and
      angular measurement to determine slip severity. Three orthopaedists obtained data
      from roentgenograms and CT of 20 hips with chronic SCFE. Statistical analysis
      showed concordance between our method and the measurements and reproducibility
      produced with CT. The results suggest that our method is as effective as and less
      expensive than CT.

PMID- 1988481
TI  - Extremity gunshot wounds in children.
AB  - A retrospective review of 85 children with extremity gunshot wounds at an average
      age of 12.3 years showed that 83% were male; there were 10 gunshot and 75 non
      shotgun injuries. Thirty-eight children sustained 51 fractures. Seventy-six
      operations were performed. The average hospital stay was 7.3 days. There were no
      mortalities, secondary amputations, or progressive neurovascular deficits. There
      were two wound infections but no cases of chronic osteomyelitis.

PMID- 1988482
TI  - Metal removal in a pediatric population: benign procedure or necessary evil?
AB  - Thirty-eight percent of patients with internal skeletal fixation had indications
      for removal other than uncomplicated healing. Plates were removed (p = 0.023)
      routinely, however, because intramedullary rods and staples were likely to be
      subcutaneous and painful (p = 0.02). Complications included incomplete removal of
      the device (7%) and two postoperative fractures. Most complications had no known
      significant adverse effects on the patients. Operative time and blood loss were
      significantly increased when a tourniquet could not be used. We believe that the
      high percentage of other indications for metal removal and the low incidence of
      major complications support the practice of routine metal removal in this
      population.

PMID- 1988483
TI  - Flexibility and anterior knee pain in adolescent elite figure skaters.
AB  - To investigate the relationship between thigh muscle flexibility and anterior
      knee pain in adolescent athletes, we examined 46 skaters. We taught them
      flexibility exercises and later retested 28 of them. Three fourths of the skaters
      who improved their quadriceps flexibility eliminated their pain. Two of the three
      skaters who lost flexibility developed pain. Analysis of all examinations showed
      that skaters with pain had tighter quadriceps muscles than those without pain.
      Poor hamstring flexibility was correlated with patellofemoral pain. This study
      shows that adolescent athletes may improve their flexibility after counseling and
      indicates a clear relationship between thigh muscle flexibility and anterior knee
      pain.

PMID- 1988484
TI  - The Bridle procedure: a new treatment for equinus and equinovarus deformities in
      children.
AB  - The Bridle procedure is a tritendon anastomosis between the posterior tibialis,
      anterior tibialis, and peroneus longus, combined with an Achilles tendon
      lengthening for treating equinus and equinovarus deformities. The technique
      avoids problems of tendon attachment to bone and tendon placement for balance.
      One hundred seven procedures were performed on patients with cerebral palsy with
      74% excellent and good results overall. The average follow-up was 5 years 9
      months. The procedure was also performed with mixed results, on smaller groups of
      patients with other neuromuscular diseases.

PMID- 1988485
TI  - Extremity lengthening: results and complications with the Orthofix system.
AB  - Twenty-four patients underwent extremity lengthening with the Orthofix for
      congenital, posttraumatic, or postinfective defects. All were followed to
      completion of treatment. Length gain and time of treatment were quite acceptable
      with the Orthofix, but the complication rate was high. This incidence was
      significantly greater than previously reported by the developers of the technique
      but equivalent to that reported with other methods.

PMID- 1988487
TI  - American College of Cardiology, 40th annual scientific session. March 3-7, 1991.
      Atlanta, Georgia. Abstracts.

PMID- 1988486
TI  - Polyostotic fibrous dysplasia and acromegaly.
AB  - A review of the recent orthopaedic literature reveals little information on the
      endocrinopathic associations of polyostotic fibrous dysplasia. This article
      illustrates the need for endocrinologic evaluations at both initial diagnosis and
      at follow-up examinations. Two patients with polyostotic fibrous dysplasia and
      acromegaly are presented. In both cases, diagnosis was made by endocrinologic and
      radiographic evaluations, including computed tomography (CT) scan of the skull.
      One patient had pituitary macroadenoma, and the other had pituitary microadenoma.
      Irradiation therapy was performed successfully in both patients without any
      complications.

PMID- 1988488
TI  - The American Academy of Allergy and Immunology, forty-seventh annual meeting. San
      Francisco, California, March 1-6, 1991. Abstracts.

PMID- 1988489
TI  - Cytokine regulation of complement receptor-mediated ingestion by mouse peritoneal
      macrophages. M-CSF and IL-4 activate phagocytosis by a common mechanism requiring
      autostimulation by IFN-beta.
AB  - Macrophage CSF (M-CSF, CSF-1) and IL-4 are two cytokines known to have effects on
      mature monocytic phagocytes in vitro. In this report we show that M-CSF and IL-4
      activate resident mouse peritoneal macrophages to ingest particles via their C3b
      and C3bi receptors, which are not capable of mediating ingestion in resting
      cells. IgG-mediated ingestion was also increased by IL-4 and M-CSF. IL-1, IL-2,
      TNF-alpha, and IFN-gamma were not able to stimulate C receptor-mediated
      ingestion. Stimulation by IL-4 and M-CSF is dependent upon high cell density and
      greater than 24-h exposure to the cytokine. Interestingly, antibody to IFN
      alpha/beta and mAb to IFN-beta inhibited the enhanced ingestion caused by both M
      CSF and IL-4. However, neither IFN-alpha nor IFN-beta alone stimulated C receptor
      mediated ingestion. M-CSF did not affect the ligand-independent distribution of
      CR3 on the macrophage surface. We conclude that two apparently unrelated
      cytokines, M-CSF and IL-4, both enhance macrophage phagocytosis of C and IgG
      coated targets via a common pathway in which autocrine stimulation with IFN
      alpha/beta is necessary but not sufficient.

PMID- 1988490
TI  - Monoclonal, but not polyclonal, antibodies protect against Plasmodium yoelii
      sporozoites.
AB  - One of the primary strategies for malaria vaccine development has been to design
      subunit vaccines that induce protective levels of antibodies against the
      circumsporozoite (CS) protein of malaria sporozoites. In the Plasmodium yoelii
      mouse model system such vaccines have been uniformly unsuccessful in protecting
      against sporozoite-induced malaria. To demonstrate that antibodies to P. yoelii
      CS protein could provide protection we established a passive transfer model.
      Passive transfer of Navy yoelii sporozoite 1 (NYS1), an IgG3 mAb against the P.
      yoelii CS protein, protected 100% of mice against challenge with 5000 P. yoelii
      sporozoites. Binding of NYS1 to sporozoites was inhibited by incubation with
      (QGPGAP)2, a synthetic peptide derived from the repeat region of the P. yoelii CS
      protein, indicating that the epitope on sporozoites recognized by this mAb was
      included within this peptide. The levels of antibodies to (QGPGAP)2 by ELISA, and
      to sporozoites by indirect fluorescent antibody test and CS precipitation
      reaction were similar in sera from mice that received NYS1 in passive transfer
      and were protected against challenge with 5000 sporozoites, and from mice that
      had been immunized with subunit vaccines containing (QGPGAP)2 but were not
      protected against challenge with 40-200 sporozoites. To determine if antibody
      avidity, not absolute concentration could explain the striking differences in
      protection, we established a thiocyanate elution assay. The results suggest that
      NYS1, the protective mAb, has a lower avidity for (QGPGAP)2 and for sporozoites
      than do the vaccine-induced antibodies. Although the results of the conventional
      antibody assays did not correlate with protection, sera from the protected
      animals inhibited sporozoite development in mouse hepatocyte cultures
      significantly more than did the sera from the unprotected, subunit vaccine
      immunized animals, correlating with protection. The data clearly demonstrate that
      antibodies to the CS protein can protect against intense sporozoite infection.
      Improved understanding of the differences between protective mAb and
      nonprotective polyclonal antibodies will be important in the further development
      of malaria vaccines.

PMID- 1988491
TI  - Expression of a novel nuclear protein in activated and in tat-I expressing T
      cells.
AB  - The intracellular events that occur in T lymphoid cells after activation or after
      infection with HIV-1 are not well defined. In the case of HIV-1 infection, it is
      unknown whether the tat-I gene, an essential gene for viral replication, affects
      host cell nuclear factors. Using two-dimensional PAGE, we have identified a novel
      nuclear protein, designated nuclear protein-28,000 (NP-28), which is induced in
      Jurkat T cells by stimulation with PMA and/or PHA or ionomycin. This nuclear
      protein has an apparent molecular mass of 28,000 Da and an isoelectric point of
      4.6. Interestingly, Jurkat cells transfected with tat-I express higher levels of
      NP-28 constitutively, without added stimulation. Incubation of Jurkat cells
      expressing tat-I with PMA and/or PHA or ionomycin causes superinduction of NP-28.
      We have therefore identified a novel lymphoid nuclear protein induced by T cell
      activation that occurs in tat-I expressing cells in the absence of activating
      agents.

PMID- 1988492
TI  - Heavy chain variable region gene families evolved early in phylogeny. Ig
      complexity in fish.
AB  - The V regions of channel catfish H chain cDNA clones have been analyzed. Based
      upon sequence relationships and hybridization analyses, five different groups of
      VH genes are identified whose definition is consistent with that of five
      different VH families. Genomic Southern blots indicate that as many as 100
      different germ-line VH genes are likely represented by these families. The
      sequence diversity between identified members of these different families is
      similar in magnitude to the divergence represented between members of different
      human or mouse VH families. The FR regions are the most conserved regions when
      members of different catfish VH families are compared; specific amino acid
      positions appear to be highly conserved in phylogeny. Equally important is that
      diversity is represented in complementarity-determining regions CDR1 and CDR2 in
      members of the different families as well as in members of the same VH family.
      These results suggest that an extensive repertoire of VH genes can contribute to
      antibody diversity in this lower vertebrate. Sequence comparisons indicate that
      one of the catfish VH families shares considerable structural similarity to
      several higher vertebrate VH gene families--a relationship which suggests that
      this VH family may be ancestral to some VH gene families of higher vertebrates.
      Characteristic of the genomic organization of higher vertebrate H chains, catfish
      appear to have different VH families wherein a VH gene likely undergoes
      functional recombination with putative DH gene segments and one of apparently
      several different JH segments. The recombined V region is expressed with the same
      C region gene. These combined results suggest that bony fishes are the earliest
      known phylogenetic representatives to have evolved extensive V region gene
      families.

PMID- 1988493
TI  - Reduced C8 beta messenger RNA expression in families with hereditary C8 beta
      deficiency.
AB  - Individuals with functional C8 beta deficiency are at increased risk for systemic
      neisserial infections. Studies by others have shown that the structural gene for
      this protein appears intact in deficient individuals. We studied affected
      individuals from 10 unrelated families to determine the basis for their defect.
      Using chain-specific antisera, C8 beta was undetectable on immunoblots of their
      sera. The polymerase chain reaction was used to probe cDNA synthesized from RNA
      isolated from human liver cells, HepG2 cells, peripheral blood monocytes, and
      fibroblasts to identify a readily available cell source expressing C8 beta
      message. Cells from each of these sources expressed C8 beta message. The identity
      of the amplified product was confirmed and this approach was used to probe cDNA
      synthesized from RNA harvested from monocytes or fibroblasts obtained from two
      unrelated families with C8 beta deficiency. C8 beta mRNA was readily detectable
      in C8 beta sufficient and heterozygous family members but required Southern
      blotting and hybridization to the 32P-labeled C8 beta probe for detection in the
      homozygous deficient probands. These results suggest that C8 beta-deficient
      individuals produce less C8 beta-specific mRNA than do normals and that the
      underlying basis for this deficiency is an abnormality in intracellular events
      that precede secretion.

PMID- 1988494
TI  - The complete exon-intron structure of a human complement component C4A gene. DNA
      sequences, polymorphism, and linkage to the 21-hydroxylase gene.
AB  - The human complement component C4A and C4B genes are located within the class III
      region of the MHC. The polymorphic C4 genes are highly complex including
      variations in class (isotype), size, and number of genes. The DNA sequence for a
      C4A gene has been determined, except for a large intron of 6 to 7 kb long. The
      C4A gene consists of 41 exons encoding a transcript for a precursor protein of
      1744 amino acid residues. Several structural and functional aspects of C4 have
      been located to individual exons. The active site of the anaphylatoxin C4a
      matches to a splice junction. Some unique properties of C4, such as, the alpha
      gamma-chain junction, the tyrosine sulfation sites, and the post-secretory
      metalloprotease cleavage site, are encoded by a single exon. Comparison of human
      C4 with published data for mouse C4, human C3 and rat alpha 2 macroglobulin genes
      revealed that these evolutionary-related genes share very similar exon-intron
      structures. Altogether 20 polymorphic sites in human C4 have been detected by
      various techniques. Presumably, these polymorphic residues account for the
      functional, structural, and serologic variations observed among the various
      allotypes. A PvuII restriction length polymorphism has been detected within the
      region of DNA coding for C4a. The intergenic region between C4 and the
      neighboring 21-hydroxylase gene, CYP21, is approximately 3028 bp in size.

PMID- 1988495
TI  - Induction of DNA fragmentation in chronic B-lymphocytic leukemia cells.
AB  - Chronic lymphocytic leukemia of B cell type (B-CLL) is a neoplastic disorder
      characterized by the accumulation of small resting lymphocytes in the periphery.
      The phenotype of these cells suggests that they are "frozen" at an early stage of
      maturation. Glucocorticoid hormones are commonly used to treat patients with B
      CLL, resulting in a reduction in the peripheral lymphocyte count by an undefined
      mechanism. Here we report that glucocorticoids stimulate DNA fragmentation
      characteristic of a suicide process known as apoptosis or programmed cell death
      (PCD) in suspensions of cells from patients with B-CLL. The effects can be
      mimicked by Ca2+ ionophore and involve a sustained increase in the cytosolic Ca2+
      concentration. Specific antibodies binding to membrane-associated IgM on the
      leukemic cells can also induce PCD by a similar mechanism. Phorbol esters block
      DNA fragmentation and cell killing in response to all of the agents, suggesting
      that activation of protein kinase C desensitizes the cells to PCD. Targeting the
      B-CLL cells with antibodies that induce an unbalanced, sustained Ca2+ increase
      may therefore represent a rational strategy for the destruction of leukemic
      cells.

PMID- 1988496
TI  - TraT: a powerful carrier molecule for the stimulation of immune responses to
      protein and peptide antigens.
AB  - A number of integral membrane proteins (Imps) isolated from Escherichia coli have
      been examined for their ability to generate serum antibody responses in the
      absence of adjuvant. These proteins were found to stimulate high titers of serum
      antibody when injected into rabbits or mice in saline. The antibody titers
      elicited were not significantly increased by the addition of a powerful adjuvant
      such as IFA. Covalent conjugation of BSA, of the DNP group, and of a peptide Ag
      from Plasmodium falciparum to these protein carriers resulted in a significant
      enhancement of the immune response to the conjugated material in comparison with
      the response elicited when the immunogen was injected without adjuvant or was not
      conjugated to Imps. The antibody response to these conjugates could not be
      significantly increased by the addition of IFA. Thus, the Imps of E. coli
      represent powerful carrier molecules which, when injected into mice and rabbits,
      are not only capable of generating high titers of antibody to themselves, but
      also to molecules conjugated to them. Immunization with immunogens coupled to
      these proteins results in the production of high titers of antibody without the
      need for oil-based adjuvants, thereby avoiding the unwanted side effects of such
      adjuvants.

PMID- 1988497
TI  - Induction of tolerance to syngeneic IgE in neonatal mice.
AB  - We have previously shown that adult A/J mice are tolerant to syngeneic IgE at the
      level of T cells, but not B cells. T cells of mice are responsive until the age
      of 2 to 3 wk, which correlates with the time of appearance of serum IgE.
      Tolerance can be induced earlier by neonatal administration of IgE in saline. We
      report here that purified nonimmune adult B cells, but not T cells, can transfer
      the state of tolerance to neonatal mice. As few as 2 x 10(6) B cells are
      effective. If IgE-bearing or IgE-secreting cells prove to be responsible, the
      amount of cell-bound IgE that can induce tolerance must be very small. The
      results also indicate that suppressor T cells do not have a major role in
      maintenance of self-tolerance to IgE.

PMID- 1988498
TI  - Growth regulation of a human mature B cell line, B104, by anti-IgM and anti-IgD
      antibodies.
AB  - An EBNA- human B lymphoma cell line, B104, was established. B104 cells express
      IgD as well as IgM on their surface, which is thought to be a basic
      characteristic of mature B cells. The growth of B104 cells was inhibited by
      treatment with a panel of anti-IgM antibodies. Cell cycle analyses revealed that
      the transition of B104 cells from the G2/M to the G0/G1 phase of the cell cycle
      was markedly inhibited by treatment with anti-IgM antibodies. Progression of B104
      cells to the M phase of the cell cycle was found to be suppressed in the presence
      of anti-IgM antibodies. In contrast, both the entrance of G0/G1 phase cells into
      the S phase and the progression of S phase cells to the G2/M phase of the cell
      cycle did not seem to be inhibited significantly by treatment with anti-IgM
      antibodies. These results indicate that the mechanism of the inhibition of growth
      of B104 cells by anti-IgM antibodies is blockage of the transition from the G2 to
      the M phase of the cell cycle. In contrast to anti-IgM antibodies, anti-IgD
      antibodies could not cause growth inhibition of B104 cells at all. B cell growth
      factors such as IL-4 and IL-6 had no effect on the inhibition of growth of B104
      cells by anti-IgM antibody. IFN-alpha and -beta, which have no B cell growth
      factor activity, did increase the number of cells that survived the treatment
      with anti-IgM antibodies. B104 is an excellent experimental model for the study
      of the mechanism of signal transduction through sIg as well as the functional
      difference between sIgM and sIgD.

PMID- 1988499
TI  - Mechanism of Staphylococcus aureus exotoxin A inhibition of Ig production by
      human B cells.
AB  - Staphylococcus enterotoxins and toxic shock syndrome toxin 1 are members of a
      family of exoproteins that are produced by staphylococci and bind specifically to
      MHC class II molecules. Upon binding to MHC class II molecules, these exoproteins
      are potent stimulators of T cell proliferation via interaction with specific TCR
      V-beta segments of both CD4+ and CD8+ T cells. These exoproteins also directly
      stimulate monocytes to secrete IL-1 and TNF-alpha. Furthermore, these exoproteins
      have a profound inhibitory effect on Ig production by PBMC. We examined the
      effects of Staphylococcus enterotoxin A (SEA) on proliferation and Ig production
      of highly purified human B cells. Our results demonstrated that the binding of
      SEA to MHC class II molecules on B cells does not alter their ability to
      proliferate in response to Staphylococcus aureus Cowan strain I (SAC) or to
      produce Ig in response to SAC plus rIL-2. In contrast, the anti-DR mAb L243
      inhibited both B cell proliferation and Ig production. Unable to determine a
      direct effect of SEA on B cell function, we investigated whether the capacity of
      SEA to inhibit SAC-induced Ig production by PBMC was T cell-dependent. Our
      results demonstrated that in the presence of T cells, under appropriate
      conditions, SEA can either function as a nominal Ag for stimulation of B cell
      proliferation and Ig production or induce T cell-mediated suppression of Ig
      production. SEA-induced Ig production required T cell help, which was dependent
      on pretreatment of the T cells with irradiation or mitomycin C; Ig production was
      not induced by SEA in the absence of T cells or in the presence of untreated T
      cells. Furthermore, SEA inhibited Ig production in SAC-stimulated cultures of
      autologous B cells and untreated T cells; pretreatment of the T cells with
      irradiation or mitomycin C abrogated SEA-induced inhibition of Ig production.
      Thus, T cell suppression of SAC-induced Ig production was dependent on T cell
      proliferation. Similar results were observed with both SEA and toxic shock
      syndrome toxin 1.

PMID- 1988500
TI  - Mechanism of hybrid resistance. The role of a natural antibody in parental bone
      marrow cell rejection.
AB  - Hybrid resistance (HR) to parental bone marrow growth is specifically directed
      against hemopoietic histocompatibility (Hh-1) Ag that are present in parental
      bone marrow cells (bmc). The mechanism of HR seems to be a multistep process.
      According to a model we proposed earlier, a T cell recognizes the Hh-1 Ag and
      stimulates a macrophage to secrete IFN-alpha/beta (recognition phase). IFN
      alpha/beta activates a NK-like cell that specifically kills the parental bmc
      (effector phase). We have also described in a previous paper that serum from
      resistant F1 hybrids contains a humoral factor that seems to be involved in the
      effector phase of HR. In the present work, we study the role and the nature of
      this humoral factor. Our results show that this humoral factor: 1) is present in
      all resistant H-2Db heterozygous F1 hybrids we have tested but not in
      nonresistant H-2Db homozygous mice; 2) seems to recognize the Hh-1b Ag because it
      is absorbed on bmc from Hh-1b mice but not on bmc from Hh-1d and Hh-1- mice; and
      3) is an IgG1 Ig (natural antibody). These results could help us to explain the
      specificity of HR at the effector phase by supposing that this natural antibody
      recognize the Hh-1 Ag and enable NK-like cells to kill parental bmc cells in Hh-1
      specific manner.

PMID- 1988501
TI  - Synergistic action of monoclonal antibodies directed at p55 and p75 chains of the
      human IL-2-receptor.
AB  - TU27, a mouse IgG1 mAb directed at the p75 chain of the human IL-2R, was analyzed
      for its ability to interact with IL-2 binding on isolated p75 chains (YT-2C2
      cells) and high affinity p55/p75 receptors (human alloreactive T cell clone 4AS),
      to inhibit IL-2-induced proliferation (4AS cells) and to cooperate with an anti
      p55 chain mAb (33B3.1) for inhibiting IL-2 binding and proliferation. TU27 and IL
      2 bound to the isolated p75 chain expressed by YT-2C2 cells with respective
      dissociation constants (Kd) of 1.3 and 1 nM. They cross-inhibited each other for
      binding with inhibition constants (Ki) in agreement with their respective Kd
      values. The nature of the interaction was, however, not purely competitive and
      suggested nonidentical epitopes for the two ligands on the p75 chain. On 4AS
      cells, IL-2 bound with high affinity (Kd = 50 pM) and TU27 with an affinity
      similar to that found on YT-2C2 cells. The binding of TU27 and IL-2 were also
      mutually exclusive on 4AS cells. However, the mechanism of interaction of TU27
      with IL-2 was complex since the inhibitory potency of the antibody depended on
      temperature, antibody preincubation and time of assay. Data obtained at 4 degrees
      C in the presence of suboptimal, tracer-like concentrations of IL-2 indicated
      that the intrinsic affinity of TU27 for the high affinity configuration was 15
      fold lower than for the isolated p75 chain and argued in favor of the affinity
      conversion model (as opposed to the preformed complex model) in which p55 and p75
      are dissociated in the absence of IL-2. At 37 degrees C, TU27 inhibited IL-2
      binding only on short time assays (6 min). Longer time (30 min) of IL-2 binding
      resulted in an almost complete disappearance of the effect of TU27, suggesting
      that internalization of the high affinity p55/p75/IL2 complex enables the cells
      to escape from the inhibitory effect of TU27. In the presence of the 33B3.1 mAb,
      the interaction of TU27 with IL-2 resembled the one observed on YT-2C2 cells,
      suggesting that 33B3.1 is able to inhibit the IL-2-induced association of p55 and
      p75. Both antibody were found to synergize on 4AS cells, as a result of a
      cooperative mechanism in which 33B3.1 blocks the formation of the high affinity
      complex hence allowing TU27 to bind with higher affinity, and TU27 blocks IL-2
      binding to the p75 chain. Proliferation studies corroborated the binding
      experiments.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1988502
TI  - A chimeric IL-2/Ig molecule possesses the functional activity of both proteins.
AB  - An expression vector (pIL-2/IgG1) was constructed with the coding sequence of
      human IL-2 inserted upstream of the four exons (CH1, hinge, CH2, and CH3) that
      encode the human IgG1 H chain constant region. Introduction of this vector into a
      nonsecreting murine myeloma cell line resulted in the production of a chimeric
      molecule (IL-2/IgG1) consisting of IL-2 attached to the three Ig constant region
      domains. This molecule was secreted by the transfectant as a homodimer.
      Functional characterization revealed that the IL-2/IgG1 chimeric molecule
      exhibited the binding and proliferation-mediating activities of IL-2. On a per
      molecule basis, IL-2/IgG1 was indistinguishable from human rIL-2 in the ability
      to induce the proliferation of an IL-2-dependent T cell line. This chimeric
      molecule also possesses Ig effector function, in that it can mediate the specific
      lysis of IL-2R-positive cells in the presence of complement. These results
      demonstrate that it is possible to maintain Ig effector function in molecules
      ("immunoligands") in which the binding specificity is conferred not by Ig
      variable regions, but rather, by a ligand of choice.

PMID- 1988503
TI  - Characterization of fragments of the murine Ia-associated invariant chain.
AB  - It has been proposed that invariant chain (Ii), a nonpolymorphic, transmembrane
      glycoprotein found in noncovalent association with Ia molecules, may function to
      protect the Ia Ag-binding site from association with self-peptides during Ia
      synthesis. Selective binding of foreign antigenic peptides could then be allowed
      by the dissociation of Ii molecules from Ia in the appropriate intracellular
      compartment. In this study, we have examined the structure and intracellular
      trafficking patterns of a putative proteolytic product of Ii, p25. We found that
      p25 is a non-membrane-bound fragment of Ii with an N terminus beginning at Met98
      of the Ii sequence. p25 is formed at a very early stage of Ii synthesis in the
      rough endoplasmic reticulum rather than in a post-Golgi Ag-processing
      compartment. We have also characterized a second Ii-related species, p28, which
      has not been reported previously. The p28 form of Ii, unlike p25, is generated
      under acidic conditions similar to those found during Ag processing.

PMID- 1988504
TI  - Paratope- and framework-related cross-reactive idiotopes on anti-acetylcholine
      receptor antibodies.
AB  - Cross-reactive idiotopes are a possible target for therapeutical interventions in
      autoimmune diseases. To investigate their role in the pathogenesis of
      experimental autoimmune myasthenia gravis (EAMG) we analyzed the Id of rat anti
      AChR mAb 6, 35, 61, 65 and a control myeloma protein IR27. Anti-Id 6, 35, 61, 65
      bound in a direct binding assay with various affinity to all rat anti-AChR mAb
      that were tested. Anti-Id IR27 recognized none of the anti-AChR mAb. The
      specificity of these crossreactions was confirmed by inhibition studies with anti
      AChR mAb and two control rat myeloma proteins (IR27 and IR241). In addition, the
      Id expression on mAb D6, a mouse anti-human AChR mAb was recognized by anti-Id 6,
      35, and 65. Anti-Id, except anti-Id IR27, bound to affinity purified IgG from the
      sera of rats with EAMG, but not to preimmune Lewis IgG. These results suggest
      extensive sharing of idiotopes among anti-AChR mAb, which are also present in
      EAMG serum. Anti-AChR mAb against the main immunogenic region (6, 35, 65) from
      different rat strains, shared at least one paratope-related cross-reactive
      idiotopes. In the view of the fact that anti-main immunogenic region antibodies
      might form a predominant fraction of the polyclonal response against AChR, it is
      conceivable that an anti-Id recognizing these antibodies could have therapeutical
      applications as for example a selective immune absorbent or in immunotoxin
      therapy.

PMID- 1988505
TI  - Kinetics of N-formyl peptide receptor up-regulation during stimulation in human
      neutrophils.
AB  - The kinetics of receptor up-regulation was examined in isolated neutrophils and
      in whole blood by flow cytometry during cell activation. Stimulation of
      neutrophils prepared without exposure to LPS with chemoattractants induced fast
      up-regulation of N-formyl peptide receptors and C receptor type 3 (CR3). Biphasic
      N-formyl peptide binding curves were detected for saturating concentrations of N
      formyl peptide at 37 degrees C. The bulk of the rapid binding during the first 30
      to 60 s is attributed to already expressed binding sites whereas the slow binding
      over the next 3 to 4 min represents a time course of receptor up-regulation.
      Support for this interpretation comes from conditions under which the number of
      binding sites and the progress of the binding curves were affected. Cells treated
      with LPS, which caused expression of internal N-formyl peptide receptors,
      exhibited rapid, monophasic binding curves with increased total binding. In LPS
      untreated, calcium-depleted cells, N-formyl peptide receptor up-regulation was
      inhibited and rapid, monophasic binding to a smaller total number of expressed
      sites was observed. Cytochalasin B enhanced the total number of available N
      formyl peptide receptors in LPS-untreated but not LPS-treated cells. In both
      cases binding was rapid and monophasic suggesting that receptors were either
      fully or rapidly up-regulated. Although not studied in real-time, C receptor type
      3 up-regulation was similar to N-formyl peptide receptor up-regulation in
      response to LPS, or stimulation by N-formyl peptide, C product C5a, leukotriene
      B4, and platelet-activating factor in isolated cells and in whole blood. After
      stimulation with formyl peptide, LPS, or C product 5a, the release of vitamin B12
      binding protein paralleled up-regulation of receptors. These data indicate that
      untreated cells up-regulate N-formyl peptide receptors during cell response at a
      rate of approximately 10,000/min in a calcium-dependent manner whereas LPS
      treated cells already express the bulk of their receptors. In cytochalasin B
      treated, degranulating cells 30,000 to 50,000 receptors were up-regulated within
      a minute.

PMID- 1988506
TI  - Safety and immunogenicity of a genetically engineered human immunodeficiency
      virus vaccine.
AB  - A phase 1 trial of a candidate human immunodeficiency virus type 1 (HIV-1)
      vaccine was done in 25 healthy seronegative subjects. The antigen, env2-3 (SF2),
      was a nonglycosylated polypeptide representing the gp120 region of the env gene
      of the HIV-1(SF2) isolate. It was produced in genetically engineered yeast as a
      denatured molecule incapable of binding CD4. A synthetic lipophilic muramyl
      tripeptide (MTP-PE) was used as an adjuvant. Ten subjects received adjuvant alone
      and 15 received 50- or 250-micrograms doses of env2-3 (SF2) administered
      intramuscularly in two immunization regimens. In general, adjuvant and vaccine
      were well tolerated. Antibody responses to both the homologous antigen, env2-3
      (SF2), and antigens from other highly divergent HIV isolates were elicited in the
      majority of vaccine recipients. However, antibody titers were low, without
      neutralizing activity. In 9 of 11 subjects who received the complete vaccine
      immunization series, a significant specific T lymphocyte response was observed.

PMID- 1988507
TI  - Pharmacokinetic disposition of zidovudine during pregnancy.
AB  - Zidovudine pharmacokinetics was determined in three human immunodeficiency virus
      type 1-seropositive women receiving zidovudine (200 mg orally every 4 h) from 19
      to 39 weeks of pregnancy and postpartum. Zidovudine concentrations were measured
      using high-pressure liquid chromatography, and pharmacokinetic analyses were done
      using model-independent methods. For the pregnant versus postpartum periods, peak
      zidovudine levels (mean +/- 1 SD) were 3.9 +/- 1.7 mumol/l versus 4.3 +/- 0.04
      mumol/l (P = .56); elimination half-lives were 1.3 +/- 0.6 versus 1.0 +/- 0.3 h
      (P = .41); areas under the concentration curve were 4.5 +/- 1.0 mumol/l x h and
      6.8 +/- 0.5 mumol/l x h (P = .02); apparent total body clearances were 2.5 +/-
      0.6 l/h/kg and 1.7 +/- 0.4 l/h/kg (P = .05); and apparent steady state volumes of
      distribution were 3.9 +/- 1.0 l/kg and 2.6 +/- 0.8 l/kg (P = .07), respectively.
      Umbilical cord serum levels ranged from 113%-127% of maternal levels. No
      persistent adverse effects of zidovudine therapy were seen in the three women or
      their babies.

PMID- 1988508
TI  - Cofactors in male-female sexual transmission of human immunodeficiency virus type
      1.
AB  - In a study of human immunodeficiency virus type 1 (HIV-1)-uninfected African
      prostitutes, 83 (67%) of 124 seroconverted to HIV-1. Oral contraceptive use (odds
      ratio [OR], 3.1; 95% confidence interval [CI], 1.1-8.6; P less than .03), genital
      ulcers (mean annual episodes, 1.32 +/- 0.55 in seroconverting women vs. 0.48 +/-
      0.21 in seronegative women; P less than .02) and Chlamydia trachomatis infections
      (OR, 3.6; CI, 1.3-11.0; P less than .02) were associated with increased risk of
      HIV-1 infection. Condom use reduced the risk of HIV-1 infection (OR, 0.11; CI,
      0.05-0.27; P less than .0001). Stepwise logistic regression analysis confirmed
      independent associations between HIV-1 infection and oral contraceptive use,
      condom use, genital ulcers, and C. trachomatis. The presence of other sexually
      transmitted diseases may in part explain the heterosexual HIV-1 epidemic in
      Africa and may represent important targets for intervention to control HIV-1
      infection.

PMID- 1988509
TI  - Human T lymphotropic virus type II (HTLV-II) infection in a cohort of New York
      intravenous drug users: an old infection?
AB  - To identify risk factors for human T lymphotropic virus type II (HTLV-II)
      infection in intravenous drug users (IVDUs), participants in a longitudinal study
      of human immunodeficiency virus (HIV) infection in a New York methadone
      maintenance program were studied. Of 270 participants tested for HTLV-I/II, 21
      (8%) were seropositive. Of those, 15 (71%) had HTLV-II-specific sequences by
      polymerase chain reaction (PCR) and 1 (5%) had both HTLV-I- and -II-specific
      sequences; 3 persons with indeterminate serologic results were also PCR-positive
      for HTLV-II. HTLV-II infection was significantly associated with older age but
      was not predicted by sex, race, socioeconomic status, transfusion history, or HIV
      infection status. Behavioral factors since 1978, such as duration and frequency
      of intravenous drug use, needle sharing, visits to shooting galleries, or number
      of sex partners, were also not associated with HTLV-II infection. These findings
      are in contrast with the association of these risk factors with HIV in this group
      and suggest that, among IVDUs, HTLV-II is an older endemic infection that is less
      efficiently transmitted than HIV.

PMID- 1988510
TI  - Antibodies to human T lymphotropic virus type I in a population from the
      Philippines: evidence for cross-reactivity with Plasmodium falciparum.
AB  - Residents of two areas in the Philippines were tested for human T lymphotropic
      virus type I (HTLV-I): Napsan, a site endemic for malaria, and a nonmalarious
      site, Bacolod. By ELISA, 30% of the 1743 Napsan residents were positive. Western
      blot immunoreactivity with two or more HTLV-I proteins was present in 81% of the
      ELISA positives; however, there was no reactivity with the env proteins. The
      frequency of this indeterminate immunoreactivity increased with the malaria
      antibody titer. None of the 200 Bacolod sera were Western blot immunoreactive. In
      competitive serologic assays, an HTLV-I lysate blocked the HTLV-I
      immunoreactivity of the Napsan sera but did not reduce malaria antibody. A
      Plasmodium falciparum lysate blocked both the HTLV-I and malaria immunoreactivity
      of the Napsan sera. These results show that indeterminate HTLV-I immunoreactivity
      can be caused by P. falciparum antibody. Serosurveys conducted in malaria endemic
      areas should consider this possibility.

PMID- 1988511
TI  - Genome analysis of adenovirus type 31 strains from immunocompromised and
      immunocompetent patients.
AB  - Adenovirus type 31 (Ad31) was isolated from 15 immunocompromised patients in 12
      of whom seroconversion was also recorded. Ad31 infection has a substantial
      clinical relevance since 8 of 10 with lower respiratory tract infection and 4 of
      4 with hepatitis died. Therefore, Ad31 isolates from immunocompetent and
      immunodeficient hosts were compared by restriction endonuclease analysis. Nine
      genome types were identified among the 79 Ad31 isolates. Pairwise comparison of
      comigrating restriction fragments indicated that the genome types could be
      divided into three genomic clusters. Several Ad31 genome types were isolated from
      immunocompromised patients, but no highly virulent genome type could be found. A
      genome type was identified in a child with severe combined immunodeficiency who
      originally was infected with another genome type. This observation is suggested
      to have evolutionary implications.

PMID- 1988512
TI  - Comparison of heterotypic protection against influenza A/Taiwan/86 (H1N1) by
      attenuated and inactivated vaccines to A/Chile/83-like viruses.
AB  - Children (n = 192) aged 3-19 years from 98 families completed this double-blind,
      placebo-controlled study comparing the efficacy of a bivalent attenuated (CR)
      vaccine with trivalent inactivated (TI) vaccine. Both vaccines contained
      A/Chile/83 (H1N1)-like antigens. After vaccination the geometric mean titer to
      A/Taiwan/86 (H1N1) was 1:36 in the CR group, 1:92 in the TI group, and 1:5 in the
      placebo group. During the influenza A/Taiwan/86 (H1N1) epidemic, 21.4% of CR
      recipients, 16.7% of TI recipients, and 43.9% of placebo recipients were infected
      with influenza A/Taiwan. TI vaccine provided better heterotypic protection than
      did CR vaccine for children aged 10-18 years (infection rate, 0 vs. 24%,
      respectively; P less than .025); in contrast, in the younger children (3-9
      years), CR vaccine tended to be more protective (19% vs. 26% for TI).

PMID- 1988513
TI  - The prevalence and incidence of clinical and asymptomatic Lyme borreliosis in a
      population at risk.
AB  - A past history of clinical Lyme borreliosis and the 6-month incidence of clinical
      and asymptomatic Lyme borreliosis was studied prospectively in a high-risk
      population. In the spring, blood samples were drawn from 950 Swiss orienteers,
      who also answered a questionnaire. IgG anti-Borrelia burgdorferi antibodies were
      detected by ELISA. Positive IgG antibodies were seen in 248 (26.1%), in contrast
      to 3.9%-6.0% in two groups of controls (n = 101). Of the orienteers, 1.9%-3.1%
      had a past history of definite or probable clinical Lyme borreliosis. Six months
      later a second blood sample was obtained from 755 participants, 558 (73.9%) of
      whom were seronegative initially; 45 (8.1%) had seroconverted from negative to
      positive. Only 1 (2.2%) developed clinical Lyme borreliosis. Among all
      participants, the 6-month incidence of clinical Lyme borreliosis was 0.8% (6/755)
      but was much higher (8.1%) for asymptomatic seroconversion (45/558). In
      conclusion, positive Lyme serology was common in Swiss orienteers, but clinical
      disease occurred infrequently.

PMID- 1988514
TI  - Randomized comparison of ceftriaxone and cefotaxime in Lyme neuroborreliosis.
AB  - In this prospective, randomized, open trial, 33 patients with Lyme
      neuroborreliosis were assigned to a 10-day treatment with either ceftriaxone, 2 g
      intravenously (iv) every 24 h (n = 17), or cefotaxime, 2 g iv every 8 h (n = 16).
      Of the 33 patients, 30 were eligible for analysis of therapeutic efficacy.
      Neurologic symptoms improved or even subsided in 14 patients of the cefotaxime
      group and in 12 patients of the ceftriaxone group during the treatment period. At
      follow-up examinations after a mean of 8.1 months, 17 of 27 patients examined
      were clinically asymptomatic. In one patient Borrelia burgdorferi was isolated
      from the cerebrospinal fluid (CSF) 7.5 months after ceftriaxone therapy. CSF
      antibiotic concentrations were above the MIC 90 level for B. burgdorferi in
      nearly all patients examined. Patients with Lyme neuroborreliosis may benefit
      from a 10-day treatment with ceftriaxone or cefotaxime. However, as 10 patients
      were symptomatic at follow-up and borreliae persisted in the CSF of one patient,
      a prolongation of therapy may be necessary.

PMID- 1988515
TI  - Antipneumococcal activity of ciprofloxacin, ofloxacin, and temafloxacin in an
      experimental mouse pneumonia model at various stages of the disease.
AB  - The efficacy of temafloxacin against Streptococcus pneumoniae in an experimental
      murine pneumonia model was compared with that of ofloxacin and ciprofloxacin.
      Erythromycin and amoxicillin were used as reference agents. Subcutaneous
      administration of antibiotics every 12 h for 3 days was initiated at various
      times after infection. The cumulative survival rates of mice treated with
      temafloxacin at 50 mg/kg were 100%, 92%, 81%, and 50% with treatment beginning
      18, 48, 72, and 96 h after infection, respectively. The activity of temafloxacin
      at 50 mg/kg was not significantly different from that of erythromycin and
      amoxicillin but was superior to that of ofloxacin and ciprofloxacin. The maximum
      cumulative survival rates of mice treated with ofloxacin and ciprofloxacin at 100
      mg/kg were 67% and 50%, respectively, with treatment beginning 18 h after
      infection. Treatment with ofloxacin and ciprofloxacin at 50 mg/kg 18 h after
      infection did not significantly increase survival rates compared with those of
      untreated controls.

PMID- 1988516
TI  - Therapy for women hospitalized with acute pyelonephritis: a randomized trial of
      ampicillin versus trimethoprim-sulfamethoxazole for 14 days.
AB  - The efficacy of the traditionally recommended ampicillin (Amp) plus gentamicin
      (GM) regimen was compared with that of a trimethoprim-sulfamethoxazole (TMP/SMZ)
      plus-GM regimen and the adequacy of 14 days total therapy for acute uncomplicated
      pyelonephritis (AUPN). Eighty-five women hospitalized for AUPN were randomly
      assigned to receive either Amp, 1 g intravenously (iv) every 6 h for 3 days, then
      500 mg orally four times daily, or TMP/SMZ, 160/800 mg iv every 12 h for 3 days,
      then 160/800 mg orally twice daily. Initially, all patients also received GM
      every 8 h iv (mean, 606 doses). Antimicrobial resistance necessitated modifying
      therapy of 14 (32%) of the Amp recipients but of none of the TMP/SMZ recipients
      (P less than .001). Both regimens produced a satisfactory bacteriologic and
      clinical response in all cases. Reinfection occurred in 11% of Amp and in 8% of
      TMP/SMZ recipients. No patient experienced relapsing infection. The TMP/SMZ
      regimen was less costly and less likely to require modification due to
      antimicrobial resistance.

PMID- 1988517
TI  - Dependence among host response parameters used to diagnose urinary tract
      infection.
AB  - The host-response parameters fever, C-reactive protein (CRP), and erythrocyte
      sedimentation rate (ESR) are activated in concert by cytokines such as
      interleukin-6 (IL-6). Il-6 is secreted in response to Escherichia coli infection
      of the urinary tract. This study tested the hypothesis that the level of fever,
      CRP, and ESR is coregulated in individual patients. Body temperature, CRP, ESR,
      pyuria, and renal concentrating capacity were analyzed in 692 children with first
      time urinary tract infections. The association of the parameters was evaluated by
      correlation and multiple regression analysis. The body temperature, CRP, and ESR
      were significantly correlated (r = .54, .58, and .58; P less than .001), and
      variation in CRP and ESR explained approximately 40% of the variation in fever.
      In contrast, the renal concentrating capacity and pyruia were weakly or not at
      all correlated with the febrile response (r = -.22; P less than .001), and less
      than 10% of the variation in renal concentrating capacity was explained by the
      other parameters. The results suggest that fever, CRP, and ESR describe the same
      aspect of the host response to UTI.

PMID- 1988518
TI  - The human humoral immune response to Salmonella typhi Ty21a.
AB  - The short-term kinetics and the effects of different dose regimens and
      formulations on the humoral immune response induced in human subjects by the live
      attenuated typhoid vaccine Salmonella typhi Ty21a were examined. Antibody
      responses in jejunal fluid and serum and by specific antibody production in vitro
      by peripheral blood lymphocytes to S. typhi lipopolysaccharide were determined. A
      short vaccination schedule of three doses of 10(11) live organisms over 5 days
      induced significantly greater intestinal IgA antityphoid antibody responses than
      did two comparable doses 21 days apart. The humoral immune response was dose
      dependent with 10(10) and 10(11) live organisms stimulating greater intestinal
      immune responses than did 10(11) killed organisms. No responses were evident with
      either 10(9) viable organisms or with an enteric-coated preparation. In the
      continued development and assessment of oral typhoid vaccines, the effects of
      different doses and formulations and the timing of sampling on the humoral immune
      response should be considered.

PMID- 1988519
TI  - Comparison of functional activities between IgG1 and IgM class-switched human
      monoclonal antibodies reactive with group B streptococci or Escherichia coli K1.
AB  - The influence of valence and heavy chain on antibody activity was investigated
      using transfectoma-derived, class-switched IgG1 and IgM human monoclonal
      antibodies (MAbs) reactive with the bacterial pathogens Escherichia coli K1 and
      group B Streptococcus species. IgG-IgM pairs were compared in vitro for antigen
      binding and opsonic activities and in vivo for protective efficacy in neonatal
      rats. For the anti-E. coli pair, the IgM MAb was 1000-fold more potent in all
      assay formats. Importantly, the 50% protection dose (PD50) of the IgM MAb was 10
      20 ng/rat, while 100 micrograms of the IgG MAb was only minimally protective. For
      the group B streptococcal MAbs, the IgM was 100- and 4500-fold more potent in
      binding and opsonization assays, respectively. However, while 20 micrograms of
      IgM protected neonatal rats, 100 micrograms of IgG MAb was partly protective.
      These experiments demonstrate the utility of recombinant DNA technology for
      creating a panel of antibodies that may aid in selecting potential
      immunotherapeutic candidates.

PMID- 1988520
TI  - Macrophage- and oxidant-mediated inhibition of the ability of live Blastomyces
      dermatitidis conidia to transform to the pathogenic yeast phase: implications for
      the pathogenesis of dimorphic fungal infections.
AB  - Conidia, produced by the mycelial phase of dimorphic fungi, are thought to
      represent the infectious form of the organism but must complete a transition to
      the tissue-invasive, yeast-like phase for infection to ensue. Preventing such
      transition should effectively eliminate pathogenicity. Using Blastomyces
      dermatitidis as a target, murine bronchoalveolar macrophages preferentially
      blocked phase transition after 4 h of incubation with conidia, relatively sparing
      the ability of conidia to produce hyphae. H2O2, in relatively high
      concentrations, demonstrated the same activity. The effects of H2O2 seem
      irreversible, since H2O2-treated conidia that germinated at 48 h at 25 degrees C
      were still unable to produce yeasts over the next 5 days when incubated at 37
      degrees C. Catalase could not reverse the macrophage-induced inhibition of phase
      transition, suggesting that nonoxidative defense mechanisms may be operative in
      vivo. Since conidia do not form mycelia at temperatures found in mammalian hosts,
      these effects may represent a novel host defense mechanism against dimorphic
      fungal pathogens.

PMID- 1988521
TI  - A comparison of 6-, 12-, and 24-monthly dosing with ivermectin for treatment of
      onchocerciasis.
AB  - This study was designed to examine the optimal dose and interval of
      administration of ivermectin, the now-accepted drug of choice for onchocerciasis.
      Two hundred Liberians with Onchocerca volvulus infection received 100, 150, or
      200 micrograms/kg ivermectin or placebo and were followed for 36 months. The
      reaction after the second dose of ivermectin was significantly less than after
      the initial dose, although it was still significant in the 200-micrograms/kg
      group. The skin microfilaria counts in the group treated 6-monthly with 150
      micrograms/kg was significantly less than in the group treated yearly (12 and 24
      months after initial therapy). Prevalence of microfilariae in the anterior
      chamber and punctate corneal opacities decreased progressively in all groups over
      3 years. There appears to be a slight advantage, in terms of antiparasitic effect
      over the first 2 years, of therapy given 6-monthly compared with yearly.

PMID- 1988522
TI  - Community-based treatment of onchocerciasis with ivermectin: safety, efficacy,
      and acceptability of yearly treatment.
AB  - The safety, acceptability, and efficacy of ivermectin during community-based mass
      treatment of onchocerciasis was assessed. Ivermectin was distributed three times,
      1 year apart, to the population of a rubber plantation (14,000 people) in Liberia
      where greater than 80% of adults have Onchocerca volvulus infection. In a sample
      of adults, the microfilarial density was reduced by 84% after 2 years of
      treatment. Acceptance was as high as 98% during the third year. Adverse reactions
      occurred in 6-13 in 1000 people after first treatment and in only 3-4 in 1000
      receiving their second or third annual dose of ivermectin; severe adverse
      reactions were not seen. These data show that community-based treatment with
      ivermectin is safe, well accepted, and effective in reducing microfilarial loads
      and suggest that ivermectin is the first practical drug suitable for mass
      treatment campaigns to control human onchocerciasis.

PMID- 1988523
TI  - Recovery of human immunodeficiency virus type 1 from semen: minimal impact of
      stage of infection and current antiviral chemotherapy.
AB  - Because exposure to semen is important for the sexual transmission of human
      immunodeficiency virus type 1 (HIV), the relationship of stage of infection and
      antiviral chemotherapy to isolation of HIV from semen was investigated. Whereas
      HIV was isolated from peripheral blood mononuclear cells of all seropositive
      persons tested, it was isolated from semen in only 11 (32%) of 34 men, including
      3 of 6 who were studied sequentially over time. HIV was isolated from 6 (32%) of
      19 semen specimens from 14 asymptomatic persons (Centers for Disease Control
      [CDC] class II or III) and from 10 (28%) of 36 semen specimens from 20
      symptomatic patients (CDC class IV). Isolation of HIV from semen did not
      correlate with CD4+ or CD8+ T lymphocytes counts or zidovudine therapy.
      Seropositive men may shed HIV in semen early in the course of infection, and
      zidovudine therapy seems to have no effect on the recovery of HIV and, thus, on
      the potential for sexual transmission of HIV.

PMID- 1988524
TI  - Detection of hepatitis B virus DNA by polymerase chain reaction in plasma of
      volunteer blood donors negative for hepatitis B surface antigen.
AB  - Plasma samples from 206 volunteer blood donors were tested for hepatitis B virus
      (HBV) DNA by dot blot hybridization and polymerase chain reaction (PCR). All
      donors were negative for hepatitis B surface antigen (HBsAg) and had normal serum
      alanine aminotransferase levels. None of the 206 plasma samples was positive for
      HBV DNA by dot blot hybridization assay. However, nine samples were positive for
      HBV DNA by PCR using two primer pairs specific for surface and core regions. Nine
      persons received the HBV-DNA-positive plasma, and one developed posttransfusion
      non-A, non-B hepatitis; the others remained well 6 months later. Therefore,
      approximately 4% of blood donors in Taiwan have low titers of HBV DNA, and a more
      sensitive method to screen donors may be needed in the future, although the
      current serologic test remains the most practical at present.

PMID- 1988525
TI  - Three new serovars of Chlamydia trachomatis: Da, Ia, and L2a.
AB  - Three new Chlamydia trachomatis serovars were identified by several monoclonal
      antibodies in the microimmunofluorescence test and are proposed to be called Da,
      Ia, and L2a. Each was clearly distinguishable from the related serovars D, I, and
      L2. To date, 7, 41, and 4 isolates of the respective serovars have been
      identified. Each appears to be distributed worldwide. The findings meet
      previously established criteria for establishment of new serovars.

PMID- 1988527
TI  - Control of nosocomial Legionnaires' disease through hot water flushing and
      supplemental chlorination of potable water.

PMID- 1988526
TI  - Combined use of released proteins and lipopolysaccharide in enzyme-linked
      immunosorbent assay for serologic screening of Yersinia infections.
AB  - An ELISA for the screening of serum antibodies to Yersinia species was developed
      using plasmid-encoded released proteins of Yersinia enterocolitica O:8 and
      lipopolysaccharide of Y. enterocolitica O:3 as a combined antigen. Of 43 sera
      from patients infected with one of six different Yersinia serotypes, 40 (93%)
      were positive in this assay. When tested using six serotype-specific ELISAs with
      the corresponding Yersinia bacteria as antigens, 38 (88%) were positive. This
      screening ELISA detects antibodies to all virulent yersiniae in one assay and
      offers the possibility for diagnosis of infections caused by Yersinia serotypes
      seen only occasionally and not usually included in the serotype-specific ELISAs.
      Thus, this ELISA offers a substantial advantage by saving time and money in
      routine laboratory work.

PMID- 1988528
TI  - Efficacy of zidovudine in preventing relapses of Salmonella bacteremia in AIDS.

PMID- 1988529
TI  - Prevalence of Chlamydia pneumoniae in Japan.

PMID- 1988530
TI  - Infectivity of Borrelia burgdorferi relative to route of inoculation and genotype
      in laboratory mice.

PMID- 1988531
TI  - Failure of fluconazole to suppress fungemia in a patient with fever, neutropenia,
      and typhlitis.

PMID- 1988532
TI  - Artifactual elevation of the serum creatinine in patients receiving flucytosine
      for cryptococcal meningitis.

PMID- 1988533
TI  - Development of a behavioral measure of mouth pain, nausea, and wellness for
      patients receiving radiation and chemotherapy.
AB  - Toxicities from the chemotherapy and irradiation preparative regimen for bone
      marrow transplantation include nausea, emesis, and oral pain. Behavioral measures
      were developed as alternatives to paper and pencil measures of these symptoms
      because patients are sometimes too ill, unavailable, or unwilling to complete
      self-report scales. Behavioral observations also provide supplements to self
      report for these multidimensional symptoms. For 24 days during the acute phase of
      transplantation, nurses rated the behavior of adult patients on: (a) oral pain
      (for example, requests pain medication or refuses mouth examination), (b) nausea
      (for instance, retches or keeps emesis basin near), (c) wellness (for example,
      talks voluntarily or smiles), (d) verbal complaints of pain, and (e) verbal
      complaints of nausea. The behavioral measures demonstrated good interday
      reliability (range, 0.70-0.86) and construct validity as demonstrated by a
      multitrait, multimethod correlation matrix.

PMID- 1988534
TI  - Systemic local anesthetics in pain control.
AB  - Analgesia has been reported as a potential effect of systemically administered
      local anesthetics for over four decades. Interest in the use of these drugs as
      analgesics has been stimulated by the advent of oral formulations and the
      findings of several controlled studies that suggest efficacy of these
      preparations in neuropathic pain syndromes. We review the pharmacology of local
      anesthetics and critically evaluate the medical literature describing the
      analgesic consequences of systemic administration. The data extant support their
      analgesic effect in selected pain syndromes.

PMID- 1988535
TI  - Evaluation of patient-controlled analgesia (PCA) versus PCA plus continuous
      infusion in postoperative cancer patients.
AB  - The benefits of two dosing methods, patient-controlled analgesia (PCA) with
      morphine sulfate (MS) alone and PCA plus continuous infusion of morphine sulfate
      (PCA + CI) were clinically evaluated in a randomized, single-blinded study of 30
      adult abdominal surgery patients. Doses were adjusted based on pain and sedation
      ratings. Respirations, pulse, blood pressure, pain and sedation ratings were
      assessed. Subjects rated their pain twice daily using a visual analog scale for
      72 hr postoperatively. The subjects reported pain relief with both dosing
      regimens. No statistically significant differences between the groups were found
      in pain and sedation ratings, or length of time using the device, with the
      exception of a higher amount of MS used on postoperative day two by the infusion
      group (p less than 0.003). There seems to be a trend for the PCA + CI group to
      have less fluctuation in sedation between days and better pain control (as
      demonstrated by verbal and visual analog pain scores) on the third postoperative
      day. Statistical significance was not found, however. PCA plus continuous
      infusion of MS may be a beneficial approach to the management of postoperative
      pain in selected patients; studies to identify these patients need to be done.

PMID- 1988536
TI  - A novel class of anti-DNA antibodies identified in BALB/c mice.
AB  - We have characterized four IgG monoclonal antibodies (mAbs) derived from BALB/c
      mice that bind double-stranded DNA (dsDNA) with high affinity. The hydridomas
      were selected for expression of a member of the VHS107 family. Three of the four
      cell lines use the VH11 gene and one uses the VH1 gene. These antibodies exhibit
      many characteristics of pathogenic anti-DNA antibodies. They are high affinity
      and not broadly crossreactive. Unlike the anti-DNA antibodies in autoimmune mice,
      they exhibit no somatic mutation in their VH genes. These results demonstrate
      that somatic mutation of VHS107 genes is not necessary for generating high
      affinity dsDNA binding. The fact that such antibodies have not previously been
      reported suggests that they are rare and that their expression may be
      downregulated in both nonautoimmune and autoimmune individuals.

PMID- 1988537
TI  - The AU-rich sequences in the 3' untranslated region mediate the increased
      turnover of interferon mRNA induced by glucocorticoids.
AB  - Different vectors were constructed that expressed the human interferon-beta (IFN
      beta) mRNA constitutively and contained various deletions in the 3' untranslated
      region (UTR). AU-rich sequences in the 3' UTR were specifically deleted in two
      vectors. Cell lines secreting human IFN-beta were established by transfecting
      murine L929 cells with the vectors. These cells showed similar levels of IFN-beta
      mRNA and secreted comparable amounts of IFN-beta, indicating that the deletion of
      AU-rich sequences had no effect on the stability and little effect on the
      efficiency of translation of this mRNA. The synthetic glucocorticoid
      dexamethasone was previously shown to increase the turnover of IFN-beta mRNA.
      This activity of dexamethasone was clearly observed only in cells expressing IFN
      beta mRNA with AU-rich sequences in the 3' UTR. The increased turnover of this
      mRNA occurred in the presence of cycloheximide; therefore, it did not require
      synthesis of new proteins. These findings suggest that glucocorticoids may
      activate a ribonuclease that degrades mRNAs containing AU-rich sequences in the
      3' UTR.

PMID- 1988538
TI  - Hydrazine sulfate protects D-galactosamine-sensitized mice against endotoxin and
      tumor necrosis factor/cachectin lethality: evidence of a role for the pituitary.
AB  - In previously published studies, we had demonstrated that hydrazine sulfate
      pretreatment protected mice against the lethal effects of endotoxin and that this
      protection was accompanied by a sustained increase in hepatic phosphoenolpyruvate
      carboxykinase activity (Silverstein, R., C.A. Christoffersen, and D.C. Morrison.
      1989. Infect. Immun. 57:2072). The same hydrazine sulfate pretreatment has now
      been found to protect mice against endotoxin in the D-galactosamine model with an
      increase in the endotoxin LD50 of approximately four orders of magnitude.
      Elimination of the pretreatment period, or administration of an additional dose
      of D-galactosamine at the time of hydrazine sulfate pretreatment, renders the
      mice refractory to the protection. Given the sensitivity of phosphoenolpyruvate
      carboxykinase regulation to several hormones, we investigated the possibility
      that protection may have been hormone mediated. In addition to determining the
      effect of hydrazine sulfate on the plasma levels of phosphoenolpyruvate
      carboxykinase regulating hormones, we have investigated the effects of hydrazine
      sulfate on endotoxin lethality in mice whose capacity to respond hormonally to
      external stimuli has been compromised by hypophysectomy. Our results show a
      significant enhancement in circulating levels of plasma corticosterone 30 min
      after hydrazine sulfate injection. Moreover, hypophysectomy results in a marked
      increase in sensitivity of mice to endotoxin challenge as well as an abrogation
      of the protection against endotoxin lethality mediated by hydrazine sulfate.
      Although hydrazine sulfate protection distinguishes between sensitivity brought
      on, individually, by D-galactosamine and by hypophysectomy, mice sensitized by
      both hypophysectomy and D-galactosamine are not protected against endotoxin
      lethality by hydrazine sulfate. We conclude that hydrazine sulfate protection
      against endotoxin lethality is endocrine dependent, with the available evidence
      implicating a pituitary/adrenal axis, with glucocorticoid involvement. In as much
      as D-galactosamine is known to act directly in the liver in disrupting protein
      synthesis, it is proposed that events in the liver are critical to the hydrazine
      sulfate-mediated protection against endotoxin and are possibly the target of the
      endocrine involvement. Hydrazine sulfate pretreatment also protects D
      galactosamine-sensitized mice against the lethal effects of injected tumor
      necrosis factor/cachectin.

PMID- 1988539
TI  - The CD4 molecule is not always required for the T cell response to bacterial
      enterotoxins.
AB  - T cells respond in a V beta-restricted fashion to bacterial enterotoxins bound to
      major histocompatibility complex (MHC) class II molecules. The requirement for
      CD4 in MHC class II-restricted T cell responses is very well established. We have
      assessed the role of CD4 in the T cell response to the bacterial enterotoxins
      Staphylococcal enterotoxin A (SEA), SEB, and toxic shock syndrome toxin 1. Three
      CD4- murine T cell hybridomas were transfected with the human CD4 molecule and
      assayed for interleukin 2 production in the presence of accessory cells bearing
      human MHC class II molecules and of the appropriate enterotoxin. The results
      clearly indicate that CD4- cells responded even to suboptimal concentrations of
      enterotoxin(s) equally well as CD4+ cells. Furthermore, expression of CD4 did not
      result in the acquisition of previously undetectable reactivity to enterotoxins.
      These results suggest that unlike the case with antigen-specific responses,
      formation of a T cell receptor-CD3/CD4 supramolecular complex is not always
      essential for T cell activation by bacterial enterotoxins.

PMID- 1988540
TI  - Identification of a 107-kD glycoprotein that mediates adhesion between stromal
      cells and hematolymphoid cells.
AB  - The mechanism of cell complex formation between lymphocytes and stromal cells was
      investigated. We found that lymphoid lines of both T and B lineages could form
      cell complexes with stromal cells from the thymus as well as bone marrow but not
      with macrophages or typical fibroblast lines. Formation of these cell complexes
      is temperature dependent and requires the presence of Mg2+, active cellular
      metabolism, and microfilament assembly of cytoskeleton. We raised an antiserum
      against a thymic stromal cell clone (BATE-2) in rats and found that, after
      absorption, this serum could effectively block cell complex formation between
      lymphocytes and stromal cells from both thymus and bone marrow. An efficient
      blocking was obtained only when the antiserum was added at the initial stage of
      cell interaction. From the blocking experiments and the SDS-PAGE analysis of
      immunoprecipitated materials from the stromal cell surface, we identified a
      unique 107-kD glycoprotein on the stromal cells as a molecule for mediating
      stromal cell-lymphocyte interaction. This is further supported by the findings
      that an antiserum raised in hamsters against the excised gel band corresponding
      to 107 kD, which specifically immunoprecipitated the 107-kD molecule, effectively
      blocked the lymphocyte-stromal cell interaction. The possible function of this
      molecule in hematolymphoid development is discussed.

PMID- 1988541
TI  - Developmental regulation of lck gene expression in T lymphocytes.
AB  - In the mouse and human, mRNA transcripts encoding the lymphocyte-specific protein
      tyrosine kinase p56lck are derived from two separate promoters resulting in
      heterogeneity in the 5' untranslated region sequence. The proximal promoter lies
      just 5' to the coding region for the gene and is active only in thymocytes. In
      contrast, the distal promoter lies 34 kilobases (kb) 5' in the human, and is
      active both in thymocytes and mature peripheral T cells. As previously reported,
      transgenic mice bearing functional proximal promoter sequence juxtaposed with the
      SV40 large T antigen gene invariably develop lymphoid tumors confined to the
      thymus. In the current work, transgenic mice bearing a 2.6-kb fragment of the
      human distal promoter fused to the SV40 large T antigen gene express large T
      antigen in thymocytes and in peripheral lymphoid cells, and develop tumors of
      both the thymus and the peripheral lymphoid organs. The ability of the human
      distal promoter to function appropriately in transgenic mice is consistent with
      the strong similarity observed between the mouse and human distal promoter
      sequences. With the exception of a single short interval that serves as a target
      for binding of nuclear factors, significant sequence similarity is not seen when
      the distal and proximal promoter sequences are compared. Hence, developmentally
      regulated, lineage-specific transcription of the lck gene is mediated by distinct
      promoter sequences that appear to be capable of functioning independently.

PMID- 1988542
TI  - Lack of feedback inhibition of V kappa gene rearrangement by productively
      rearranged alleles.
AB  - Circular DNAs excised by immunoglobulin kappa chain gene rearrangements were
      cloned and characterized. 16 of 17 clones examined were double recombination
      products containing a V kappa-J kappa rearrangement (coding joint) as well as the
      reciprocal element (signal joint) of another V kappa-J kappa rearrangement. These
      products suggested multiple recombination, primary inversion, and secondary
      excision. In primary events, 5 of 16 translational reading frames were in-phase.
      Thus, V kappa gene rearrangement may not be inhibited by the presence of a
      productively rearranged allele. An unusually large trinucleotide (P) insertion
      forming a palindrome of 12 nucleotides was also observed in one of the coding
      joints.

PMID- 1988544
TI  - Extrahepatic transcription of human C-reactive protein.
AB  - We synthesized and cloned cDNA from human peripheral blood mononuclear cell
      (PBMC) transcripts that were hybrid selected by pCRP5, a liver C-reactive protein
      (CRP)-specific cDNA (Woo, P.,J.R. Korenberg, and A.S. Whitehead. 1985. J.Biol.
      Chem. 260:13384). Three hybrid-selected cDNA clones, HScDNA1, HScDNA3, and
      HScDNA8, were isolated and characterized. Nucleotide sequence analysis of the 5'
      end of the smaller clones, HScDNA1 and HScDNA8, demonstrated that these two PBMC
      clones are homologous to the 3' and 5' ends, respectively, of pCRP5. Our largest
      clone, HScDNA3, is larger than pCRP5, extending beyond both the 5' and 3' limits
      of pCRP5. Therefore, HScDNA3 was coded by human PBMC and not by the hybrid
      selection vehicle, pCRP5. HScDNA3 lacks the intervening sequence verifying that
      this clone is DNA made from a PBMC mRNA and not genomic DNA. The complete
      nucleotide sequence revealed that HScDNA3 is greater than 99% homologous to the
      CRP gene. These results demonstrate that PBMC express the CRP gene. Based on our
      previous report, which shows that peripheral blood cells synthesize a peptide
      recognized by anti-CRP (Kuta, A.E., and L.L. Baum. 1986. J. Exp. Med. 164:321),
      in conjunction with the data presented here, we conclude that human PBMC can
      synthesize CRP.

PMID- 1988543
TI  - Transgenic mice expressing a B cell growth and differentiation factor gene
      (interleukin 5) develop eosinophilia and autoantibody production.
AB  - Interleukin 5 (IL-5) has been suggested to be involved in the growth and
      differentiation of B cells and eosinophils. Especially, Ly-1+ B cells, which have
      been considered to produce autoantibodies, are selectively developed by this
      lymphokine in long-term bone marrow culture. To envisage the possible engagement
      of IL-5 in the development of these cells in vivo, transgenic mice carrying the
      mouse IL-5 gene ligated with a metallothionein promoter were generated.
      Transgenic mice carrying the IL-5 gene exhibited elevated levels of IL-5 in the
      serum and an increase in the levels of serum IgM and IgA. A massive eosinophilia
      in peripheral blood, bone marrow, and spleen, and an infiltration of muscle and
      liver with eosinophils, were observed. When cadmium-containing saline was
      injected intraperitoneally into transgenic mice, IL-5 production was augmented
      about five times within 24 h, and a distinctive Ly-1+ B cell population became
      apparent in the spleen after 5 d. IL-5 receptors were detected on those cells by
      monoclonal antibodies against IL-5 receptors. Another interesting finding in
      these transgenic mice was an increase in polyreactive anti-DNA antibodies of IgM
      class. It is suggested, therefore, that aberrant expression of the IL-5 gene may
      induce accumulation of Ly-1+ B cells and eosinophils. Furthermore, this IL-5
      transgenic mouse can be a model mouse for eosinophilia, and we can determine the
      role of IL-5 in the differentiation of Ly-1+ B cells and eosinophils by using
      this mouse.

PMID- 1988545
TI  - Calcium effects on the solubilization of membrane-bound histidine decarboxylase
      in the rat brain.
AB  - In a previous work we have shown that histidine decarboxylase (HD) activity is
      found in a soluble and a membrane-bound form. A major part (82%) of the membrane
      bound HD activity in the crude mitochondrial fraction (P2) was present in the
      synaptic plasma membrane-containing subfraction. Physiological concentrations of
      Ca2+ had no direct effect on HD activity but caused a solubilization of
      approximately 50% of membrane-bound HD in the P2 fraction. Mg2+ had similar but
      lower effects (20% solubilization) than Ca2+. Incubation with depolarizing
      concentrations of K+ in the presence of 1 mM CaCl2 caused a significant (30%)
      solubilization of HD.

PMID- 1988546
TI  - Expression of various microtubule-associated protein 2 forms in the developing
      mouse brain and in cultured neurons and astrocytes.
AB  - A cDNA probe specific to microtubule-associated protein 2 (MAP2) was used to
      study the expression of the mRNAs encoding the high- and low-molecular-weight
      MAP2 variants in cultured neurons and astrocytes. The timing and relative
      abundance of these MAP2 transcripts and of their encoded proteins were also
      studied in the developing cerebral hemispheres and cerebellum of the mouse. A 9
      kb mRNA, known to encode high-molecular-weight MAP2, was expressed in cultured
      astrocytes, albeit at a lower level than in neurons. The 6-kb transcript,
      recently shown to encode low-molecular-weight MAP2 (MAP2c), was expressed in
      neurons and was the predominant MAP2 transcript of the astrocytes. The level of
      the 9- and 6-kb transcripts decreased at late stages of astroglial and neuronal
      cell culture. The 9-kb mRNA was detected in the cerebellum and cerebral
      hemispheres at every developmental stage. Although the levels of this mRNA varied
      slightly in the cerebral hemispheres, its expression was biphasic in the
      cerebellum. This might be explained by the differences in timing of development
      of the various neuronal cell types formed in these two brain areas. The 6-kb
      transcript was detected only at early developmental stages in the two brain
      areas. Correlating the temporal expression of the 9-kb mRNA to that of high
      molecular-weight MAP2 indicates that the accumulation of this protein is in part
      regulated at a cytoplasmic level.

PMID- 1988548
TI  - Iron and aluminum increase in the substantia nigra of patients with Parkinson's
      disease: an X-ray microanalysis.
AB  - The levels of different elements were studied by x-ray microanalysis in the
      substantia nigra and the central gray substance of patients with Parkinson's
      disease, progressive supranuclear palsy, and matched controls. In control brains,
      only iron, potassium, silicum, sodium, sulfur, and zinc were within the limit of
      detection of the technique. The abundance of each element was different, but
      their respective concentrations in the two brain regions were similar, except for
      sulfur levels which were higher on neuromelanin aggregates in the substantia
      nigra than in nigral regions lacking neuromelanin, and in the central gray
      substance. In Parkinson's disease, but not in progressive supranuclear palsy,
      nigral iron levels increased in regions devoid of neuromelanin and decreased on
      neuromelanin aggregates, but were unchanged in the central gray substance, when
      compared to control values. Concentrations of the other elements in the central
      gray substance and substantia nigra were not different from controls in brains
      from patients with Parkinson's disease and progressive supranuclear palsy.
      Analysis of Lewy bodies in the parkinsonian substantia nigra revealed high levels
      of iron and the presence of aluminum. Metal abundance was not affected in
      progressive supranuclear palsy, in spite of the nigral cell death. This suggests
      that the increased iron levels and the detection of aluminum observed in
      Parkinson's disease are not solely the consequence of the neuronal degeneration.

PMID- 1988547
TI  - Vitamin C deficiency facilitates 5-S-cysteinyldopamine formation in guinea pig
      striatum.
AB  - Being a catechol, dopamine (DA) is easily autoxidized in solution to a
      semiquinone and then further to a quinone. These quinones and by-products, as
      reduced forms of oxygen, are all cytotoxic. By quantifying quinone metabolites,
      such as 5-S-cysteinyl adducts of DA, 3,4-dihydroxyphenylalanine (DOPA), and 3,4
      dihydroxyphenylacetic acid (DOPAC), an indirect measure of catechol autoxidation
      is available. Ascorbic acid (AA) has an important role as an antioxidant in the
      organism. A group of guinea pigs (Dunkin-Hartley) received an AA-free diet for 37
      days, whereas a control group was fed an AA-containing diet (1,400 mg/kg of
      pellets). To one group of AA-deprived animals a single dose of AA (500 mg/kg,
      i.p.) was administered 2 h before death, whereas another group received two doses
      9 and 24 h before death. The striatal levels of 5-S-cysteinyl adducts, DA,
      noradrenaline, and DOPAC and the cerebellar and the limbic levels of AA were
      determined. A significant increase in 5-S-cysteinyl-DA content was found in the
      striatum of AA-deficient animals (143 +/- 12% of control values). A further
      increase was found 2 h after an AA injection (177 +/- 16% of control values),
      which was significant compared with both controls and AA-deficient animals. An
      elevation in 5-S-cysteinyl-DA content was still observed following two AA
      injections during a 24-h period (153 +/- 7% of control values). The 5-S-cysteinyl
      DOPAC content increased significantly (134 +/- 14% of control values) in the AA
      deficient animals given AA acutely (2 h), both compared with controls and with
      the AA-deficient group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1988549
TI  - Effect of varying the ionic concentration of a microdialysis perfusate on basal
      striatal dopamine levels in awake rats.
AB  - In vivo microdialysis was used to study the effects of Ca2+, Mg2+, and K+ ion
      concentrations on basal extracellular (EC) levels of striatal DA and metabolites
      in awake rats on the second day (48 h) after implantation of a microdialysis
      probe. Basal EC striatal dopamine (DA) levels were markedly (90%) and reversibly
      reduced by removal and subsequent replacement of Ca2+ ions from the microdialysis
      perfusate. This implies that the EC DA in this preparation is primarily of
      synaptic origin. The addition and subsequent removal of 1.7 mM MgCl2 to the
      Mg2(+)-free perfusate produced a reversible decrease (20%) in basal EC DA levels.
      This decrease may reflect a competitive interaction between Ca2+ and Mg2+ in the
      process of vesicular release. Basal EC DA levels were also reduced (27%) by
      decreasing the K+ concentration of the perfusate from 4 mM to 3 mM. However,
      after restoring the K+ concentration to 4 mM, EC DA levels were slow to return to
      pretreatment levels. Basal EC 3,4-dihydroxyphenylacetic acid and homovanillic
      acid levels exhibited a parallel but diminished response to each manipulation of
      the ionic concentration of the perfusate. This study demonstrates that small
      variations in the concentrations of Ca2+, Mg2+, and K+ in the perfusate employed
      in microdialysis preparations will affect basal EC striatal DA and metabolite
      levels.

PMID- 1988550
TI  - Developmental regulation of beta-thymosins in the rat central nervous system.
AB  - HPLC analysis of guanidinium hydrochloride extracts of neonatal and adult rat
      brain revealed a polypeptide that is present in high concentration in the
      immature nervous system, but whose levels decline dramatically in the adult. This
      polypeptide has been isolated and its complete amino acid sequence determined by
      gas-phase Edman degradation following specific chemical and enzymatic cleavages.
      The molecule is identified as thymosin beta 10, a member of a multigene family
      that encodes a structurally conserved series of small acidic polypeptides of
      uncertain function. Thymosin beta 10 is present in the developing nervous system
      as early as embryonic day 9. Levels subsequently increase to peak values between
      embryonic day 15 and postpartum day 3, before falling to adult values (about a 20
      fold reduction) by postpartum day 14. The elevated levels of thymosin beta 10 in
      fetal and neonatal brain correlate with high levels of thymosin beta 10 mRNA,
      whereas the low values of the polypeptide in the adult and juvenile are mirrored
      by an approximate 15-fold reduction in specific mRNA. In comparison, the levels
      of thymosin beta 4 polypeptide, a homologue of thymosin beta 10, only decline by
      about 20% during the same developmental period. However, the mRNA encoding
      thymosin beta 4 is elevated in fetal brain, and its levels decrease approximately
      four-fold to a stable value around the time of birth. The reason for this
      discrepancy between thymosin beta 4 protein and mRNA levels is unknown. Thymosin
      beta 10 can also be detected by HPLC in fetal liver, where levels are
      approximately 5% of those in brain. In liver, thymosin beta 10 also declines
      following birth. It is concluded that beta-thymosin expression (as measured by
      steady-state mRNA and polypeptide levels) is both up- and down-regulated during
      different phases of maturation of the mammalian nervous system.

PMID- 1988551
TI  - 65Zn uptake from blood into brain in the rat.
AB  - Zinc is essential for the normal development and function of the CNS, although
      little is known about brain zinc homeostasis. Therefore, in this investigation we
      have studied 65Zn uptake by brain from blood and have measured the blood-brain
      barrier permeability to 65Zn in the anaesthetised rat in vivo. Adult male Wistar
      rats within the weight range 500-600 g were used. 65ZnCl2 and 125I-albumin, the
      latter serving as a vascular marker, were injected intravenously in a bolus of
      normal saline. Sequential arterial blood samples were taken during experiments
      that lasted between 5 min and 5 h, after which the whole brain was removed,
      dissected, and analysed for radioisotope activity. Data have been analysed by
      graphical analysis, which suggests that after 30 min of circulation, 65Zn uptake
      by brain from blood is unidirectional with an influx rate constant, Kin, of
      approximately 5 X 10(-4) ml/min/g. At circulation times of less than 30 min, 65Zn
      fluxes between blood and brain are bidirectional, where influx has a K value of
      greater than 5 X 10(-4) ml/min/g. In addition to the blood space, the brain
      appears to contain a rapidly exchanging compartment(s) for 65Zn of approximately
      4 ml/100 g, which is not CSF.

PMID- 1988552
TI  - [3H]harman binding experiments. I: A reversible and selective radioligand for
      monoamine oxidase subtype A in the CNS of the rat.
AB  - Harman (1-methyl-beta-carboline) is an endogenous compound with neurotropic
      properties in rats and humans. In a novel in vitro binding assay, the binding
      site of [3H]harman has been characterized in the rat crude mitochondrial (P2)
      fraction. The binding was saturable and reversible. Only a single high-affinity
      binding site was detected by kinetic, saturation, and displacement analyses in
      the cerebral cortex of the rat. The linear Scatchard plots revealed equilibrium
      dissociation constant (KD) values of approximately 2.5 nM at 0 degrees C,
      approximately 9 nM at 23 degrees C, and approximately 30 nM at 37 degrees C.
      Among six CNS regions (hypothalamus, hippocampus, cerebral cortex, striatum,
      cerebellum, and spinal cord), the highest density of binding sites (Bmax) was
      determined in the hypothalamus (approximately 5.5 pmol/mg of protein) and the
      lowest in the spinal cord (approximately 2.0 pmol/mg of protein). Several drugs
      known to affect serotonergic, adrenergic, dopaminergic, cholinergic, or GABAergic
      neurotransmission inhibited specific binding at best in the micromolar range. In
      contrast, potent and selective inhibitors of monoamine oxidase subtype A were
      active in the lower and middle nanomolar range. The displacing potency (apparent
      Ki) of substrates and inhibitors of monoamine oxidase correlated positively and
      highly significantly with the corresponding values of the inhibition of monoamine
      oxidase activity of subtype A (r = 0.92, p less than 0.001, n = 17) but not of
      subtype B (r = -0.47, p greater than 0.05, n = 15). In conclusion, [3H]harman was
      identified as a specific ligand of the active site of the A subtype of monoamine
      oxidase in rat brain.

PMID- 1988553
TI  - [3H]harman binding experiments. II: Regional and subcellular distribution of
      specific [3H]harman binding and monoamine oxidase subtypes A and B activity in
      marmoset and rat.
AB  - [3H]Harman (1-[3H]methyl-beta-carboline) was used in a novel radioligand binding
      assay to label selectively and with high affinity monoamine oxidase (MAO) type A.
      The concentration of the enzyme was determined in six CNS regions of the primate
      species marmoset (Callithrix jacchus) and of the rat: hypothalamus, hippocampus,
      cerebellum, cerebral cortex, striatum, and spinal cord. The specific [3H]harman
      binding in the CNS of the marmoset reveals the same pharmacological profile and
      other characteristics (affinity, saturability, and reversibility) as in the CNS
      of the rat. The regional distribution of the [3H]harman binding density (Bmax) in
      the CNS exhibits a distinct pattern in the marmoset and the rat and a 35
      (hypothalamus) to 75% (hippocampus) lower Bmax in the marmoset than in the rat.
      The Bmax values of [3H]harman binding in the CNS of the marmoset and the rat
      combined as well as those from visceral organs of the rat (liver, heart, lung,
      thymus, spleen, and kidney) correlated positively and highly significantly with
      the respective Vmax values of specific MAO activity of the A type but not of the
      B type, determined with kynuramine as the substrate. In subcellular fractionation
      experiments with rat cerebral cortex, the highest [3H]harman binding density
      (Bmax) and MAO-A activity (Vmax) were detected in mitochondrial fractions and
      severalfold lower values in the synaptosomal membrane fraction. In conclusion, we
      suggest that [3H]harman binding is a biochemical tool as a selective marker to
      quantify MAO-A in the CNS of different mammalian species as well as in
      extraneuronal tissues.

PMID- 1988554
TI  - Bradykinin activates a phospholipase D that hydrolyzes phosphatidylcholine in
      PC12 cells.
AB  - In PC12 pheochromocytoma cells whose phospholipids had been prelabelled with
      [3H]palmitic acid, bradykinin increased the production of [3H]phosphatidic acid.
      The increase in [3H]phosphatidic acid occurred within 1-2 min. before the
      majority of the increase in [3H]diacylglycerol. When the phospholipids were
      prelabeled with [3H]choline, bradykinin increased the intracellular release of
      [3H]choline. The production of phosphatidic acid and choline suggests that
      bradykinin was increasing the activity of phospholipase D. Transphosphatidylation
      is a unique property of phospholipase D. In cells labeled with [3H]palmitic acid,
      bradykinin stimulated the transfer of phosphatidyl groups to both ethanol and
      propanol to form [3H]phosphatidylethanol and [3H]phosphatidylpropanol,
      respectively. The effect of bradykinin on [3H]phosphatidic acid and
      [3H]phosphatidylethanol formation was partially dependent on extracellular Ca2+.
      In cells treated with nerve growth factor, carbachol also increased
      [3H]phosphatidylethanol formation. To investigate the substrate specificity of
      phospholipase D, cells were labeled with [14C]stearic acid and [3H]palmitic acid,
      and then incubated with ethanol in the absence or presence of bradykinin. The
      14C/3H ratio of the phosphatidylethanol that accumulated in response to
      bradykinin was almost identical to the 14C/3H ratio of phosphatidylcholine. The
      14C/3H ratio in phosphatidic acid and diacylglycerol was higher than the ratio in
      phosphatidylcholine. These data provide additional support for the idea that
      bradykinin activates a phospholipase D that is active against
      phosphatidylcholine. The hydrolysis of phosphatidylcholine by phospholipase D
      accounts for only a portion of the phosphatidic acid and diacylglycerol that
      accumulates in bradykinin-stimulated cells: bradykinin evidently stimulates
      several pathways of phospholipid metabolism in PC12 cells.

PMID- 1988556
TI  - L-[3H]adenosine, a new metabolically stable enantiomeric probe for adenosine
      transport systems in rat brain synaptoneurosomes.
AB  - The stereoenantimers D-[3H]adenosine and L-[3H]adenosine were used to study
      adenosine accumulation in rat cerebral cortical synaptoneurosomes. L-Adenosine
      very weakly inhibited rat brain adenosine deaminase (ADA) activity with a Ki
      value of 385 microM. It did not inhibit rat brain adenosine kinase (AK) activity,
      nor was it utilized as a substrate for either ADA or AK. The rate constants
      (fmol/mg of protein/s) for L-[3H]adenosine accumulation measured in assays where
      transport was stopped either with inhibitor-stop centrifugation or with rapid
      filtration methods were 82 +/- 14 and 75 +/- 10, respectively. Using the
      filtration method, the rates of L-[3H]adenosine accumulation were not
      significantly different from the value of 105 +/- 15 fmol/mg of protein/s
      measured for D-[3H]adenosine transport. Unlabeled D-adenosine and
      nitrobenzylthiolnosine, both at a concentration of 100 microM, reduced the levels
      and rates of L-[3H]adenosine accumulation by greater than 44%. These findings
      suggest that L-adenosine, a metabolically stable enantiomeric analog, and the
      naturally occurring D-adenosine are both taken up by rat brain synaptoneurosomes
      by similar processes, and as such L-adenosine may represent an important new
      probe with which adenosine uptake may be studied.

PMID- 1988555
TI  - Enhanced rate of expression and biosynthesis of neuropeptide Y after kainic acid
      induced seizures.
AB  - Recent studies have shown marked increases in brain content of neuropeptide Y
      (NPY) after seizures induced by intraperitoneal injection of kainic acid and
      after pentylenetetrazole kindling in the rat. We have now investigated possible
      changes in the rate of biosynthesis of NPY after kainic acid treatment, by using
      pulse-labeling of the peptide and by determining prepro-NPY mRNA concentrations.
      For pulse labeling experiments, [3H]tyrosine was injected into the frontal
      cortex, and the incorporation of the amino acid into NPY was determined after
      purifying the peptide by gel filtration chromatography, antibody affinity
      chromatography, and reversed-phase HPLC. At 2 and 30 days after kainic acid
      treatment, the rate of tyrosine incorporation was enhanced by approximately 380%
      in the cortex. In addition, concentrations of pre-pro-NPY mRNA were determined in
      four different brain areas by hybridization of Northern blots with a
      complementary 32P-labeled RNA probe 2, 10, 30, and 60 days after kainic acid
      treatment. Marked increases were observed in the frontal cortex (by up to 350% of
      controls), in the dorsal hippocampus (by 750%), and in the amygdala/pyriform
      cortex (by 280%) at all intervals investigated. In the striatum only a small,
      transient increase was observed. The data demonstrate increased expression of
      prepro-NPY mRNA and an enhanced rate of in vivo synthesis of NPY as a result of
      seizures induced by the neurotoxin kainic acid.

PMID- 1988557
TI  - Relationship between [3H]mazindol binding to dopamine uptake sites and
      [3H]dopamine uptake in rat striatum during aging.
AB  - Certain drugs exhibit a remarkable correlation between their ability to inhibit
      synaptosomal uptake of dopamine and the binding of [3H]mazindol to striatal
      membranes. To investigate the role of mazindol binding sites in the dopamine
      uptake process and the fate of these sites (labeling dopaminergic neurons) during
      aging, we have examined the properties of mazindol binding and dopamine uptake in
      individual young and old rats. There was a 48% decrease (p = 0.0001) in the Bmax
      of mazindol binding and a 23% decrease (p = 0.0166) in the Vmax of dopamine
      uptake with no apparent change in their affinities with age. Regression analysis
      of the relationship between Bmax and Vmax exhibited a significant correlation in
      old (p = 0.0156) but not young rats (p = 0.1398). These data suggest that the
      number of mazindol binding sites decreases with age and that the number of sites
      on the dopamine transporter complex far exceeds the number required to elicit
      maximal dopamine uptake.

PMID- 1988558
TI  - Nicotine indirectly inhibits [3H]dopamine uptake at concentrations that do not
      directly promote [3H]dopamine release in rat striatum.
AB  - The effects of both (-)- and (+)-nicotine isomers were examined on in vitro
      uptake and release of [3H]dopamine in rat striatum. Both isomers inhibited uptake
      of [3H]dopamine in chopped tissue at concentrations well below those necessary
      for promoting release of preloaded [3H]dopamine. (-)-Nicotine was more potent
      than (+)-nicotine both at inhibiting uptake and at promoting release. Unlike
      other dopamine uptake inhibitors, however, nicotine inhibited only 50% of the
      total uptake. In the presence of 1 nM nicotine, the residual [3H]dopamine uptake
      was less sensitive to inhibition by cocaine than uptake in the absence of
      nicotine. Nicotine did not compete against the binding of [3H]GBR 12935, a
      selective dopamine uptake inhibitor. The nicotinic receptor agonists carbachol
      and 1,1-dimethyl-4-phenylpiperazinium iodide also inhibited uptake, whereas the
      nicotinic antagonists chlorisondamine and mecamylamine blocked nicotine's effect.
      Thus, the effect of nicotine on dopamine uptake appears to be mediated by a
      receptor similar to the nicotinic acetylcholine receptor. These receptors do not
      seem to be on the terminals that are accumulating dopamine, however, since
      tetrodotoxin prevented the effect of nicotine on [3H]dopamine uptake and nicotine
      had no effect on uptake in a synaptosomal preparation.

PMID- 1988559
TI  - Rat brain free glucose and lactate measurement by a novel method using bisecting
      decapitation-extrusion and enzyme denaturation at five seconds.
AB  - This study investigates a novel method as a means for animal decapitation with
      rapid brain removal and enzyme denaturation. Briefly, the rat head is
      simultaneously decapitated and bisected. Either half of the in situ brain is
      aspirated under -250 mm Hg pressure into a modified small plastic syringe and
      then extruded through a needle as a fine strand into a relatively large volume of
      2 M urea at 95 degrees C. After cooling, sonication, and centrifugation of the
      brain homogenate, the supernatant is measured enzymatically for brain free
      glucose and lactate concentration. Enzyme denaturation is effected within 4-6 s.
      The results are in good agreement with published values for glucose and lactate
      using other rapid enzyme inactivation techniques.

PMID- 1988560
TI  - Adrenal medullary transplants increase spinal cord cerebrospinal fluid
      catecholamine levels and reduce pain sensitivity.
AB  - Previous work in this laboratory has shown that adrenal medullary transplants
      into the spinal cord subarachnoid space can reduce pain sensitivity. This
      analgesia most likely results from the release of neuroactive substances,
      particularly catecholamines and opioid peptides, from the transplanted cells into
      the CSF of the spinal cord, since it can be attenuated or blocked by alpha
      adrenergic or opiate antagonists. The purpose of the present study was to more
      directly measure the release of catecholamines from adrenal medullary transplants
      in the spinal cord CSF using a spinal superfusion technique. CSF samples from
      rats with 6-month-old transplants were assayed for catecholamines using HPLC with
      electro-chemical detection. Results indicated that norepinephrine levels were
      increased threefold, and epinephrine levels nearly 100-fold, in animals with
      adrenal medullary transplants compared with control transplanted animals. There
      was no apparent increase in dopamine levels. Furthermore, the increased levels of
      total catecholamines were correlated with decreased pain sensitivity. Results of
      this study indicate that adrenal medullary transplants can survive for long
      periods in the rat spinal CSF and continue to release high levels of
      catecholamines. Together, the release of catecholamines and opioid peptides from
      adrenal medullary transplants may provide the ideal combination for the reduction
      of pain.

PMID- 1988561
TI  - Regulation by interleukin-1 of nerve growth factor secretion and nerve growth
      factor mRNA expression in rat primary astroglial cultures.
AB  - Primary cultures of neonatal rat cortical astrocytes contain low cellular levels
      (about 2 pg/mg of protein) of nerve growth factor (NGF), but secrete significant
      amounts of NGF into the culture medium (about 540 pg of NGF/mg of cell protein/38
      h incubation). Incubation of astrocytes with interleukin-1 (IL-1) increased the
      cellular content of NGF and the amount secreted by about threefold. In
      comparison, cerebellar astrocytes secreted significant amounts of NGF, and the
      secretion was also stimulated by IL-1. The stimulatory action of IL-1 on
      astrocytes prepared from cortex was dose- and time-dependent. Concentrations of
      IL-1 causing half-maximal and maximal stimulation of NGF secretion were 1 and 10
      U/ml, respectively). Maximal NGF secretion induced by IL-1 (10 U/ml) was seen
      following 38 h of incubation. The basal secretion of NGF was reduced by about 50%
      under Ca2(+)-free conditions; however, the percent stimulation of NGF secretion
      by IL-1 was the same in the absence or presence of Ca2+. The stimulatory action
      of IL-1 was specific, because other glial growth factors and cytokines were
      almost ineffective in stimulating NGF secretion from cortical astroglial cells.
      IL-1 treatment also increased cellular NGF mRNA content twofold. The results
      indicate that IL-1 specifically triggers a cascade of events, independent of cell
      growth, which regulate NGF mRNA content and NGF secretion by astrocytes.

PMID- 1988562
TI  - GTP and Ca2+ modulate the inositol 1,4,5-trisphosphate-dependent Ca2+ release in
      streptolysin O-permeabilized bovine adrenal chromaffin cells.
AB  - The inositol 1,4,5-trisphosphate (IP3)-induced Ca2+ release was studied using
      streptolysin O-permeabilized bovine adrenal chromaffin cells. The IP3-induced
      Ca2+ release was followed by Ca2+ reuptake into intracellular compartments. The
      IP3-induced Ca2+ release diminished after sequential applications of the same
      amount of IP3. Addition of 20 microM GTP fully restored the sensitivity to IP3.
      Guanosine 5'-O-(3-thio)triphosphate (GTP gamma S) could not replace GTP but
      prevented the action of GTP. The effects of GTP and GTP gamma S were reversible.
      Neither GTP nor GTP gamma S induced release of Ca2+ in the absence of IP3. The
      amount of Ca2+ whose release was induced by IP3 depended on the free Ca2+
      concentration of the medium. At 0.3 microM free Ca2+, a half-maximal Ca2+ no Ca2+
      release was observed with 0.1 microM IP3; at this Ca2+ concentration, higher
      concentrations of IP3 (0.25 microM) were required to evoke Ca2+ release. At 8
      microM free Ca2+, even 0.25 microM IP3 failed to induce release of Ca2+ from the
      store. The IP3-induced Ca2+ release at constant low (0.2 microM) free Ca2+
      concentrations correlated directly with the amount of stored Ca2+. depending on
      the filling state of the intracellular compartment, 1 mol of IP3 induced release
      of between 5 and 30 mol of Ca2+.

PMID- 1988563
TI  - Cocaethylene: a unique cocaine metabolite displays high affinity for the dopamine
      transporter.
AB  - Concurrent cocaine and alcohol use is common practice in the general population,
      as indicated by recent prevalence studies. In the presence of ethyl alcohol,
      cocaine is metabolized to its ethyl homolog, cocaethylene. The
      transesterification of cocaine and ethanol to cocaethylene takes place in the
      liver and represents a novel metabolic reaction. Cocaethylene was detected in
      postmortem blood, liver, and neurological tissues in concentrations equal to and
      sometimes exceeding those of cocaine. In vitro binding studies demonstrate that
      cocaethylene has a pharmacological profile similar but not identical to that of
      cocaine at monoamine transport sites assayed in the human brain. Cocaethylene was
      equipotent to cocaine at inhibiting [3H]mazindol binding to the dopamine
      transporter. The blockade of dopamine reuptake in the synaptic cleft by
      cocaethylene may account for the enhanced euphoria associated with combined
      alcohol and cocaine abuse.

PMID- 1988564
TI  - Core protein of chondroitin sulfate proteoglycan promotes neurite outgrowth from
      cultured neocortical neurons.
AB  - Chondroitin sulfate proteoglycan (CS-PG) was purified from rat brain and examined
      for its effect on neurite outgrowth in primary cultures of embryonic rat
      neocortical neurons. Neurite outgrowth was increased in culture wells coated with
      CS-PG. The core protein and glycosaminoglycan (GAG) prepared from the CS-PG were
      also examined for neurite-promoting activity. The activity was observed in
      culture wells coated with the core protein but not with GAG. These results
      suggest that CS-PG stimulates neurite outgrowth from the cultured neurons via its
      core protein.

PMID- 1988565
TI  - Expression and agonist-induced down-regulation of mRNAs of m2- and m3-muscarinic
      acetylcholine receptors in cultured cerebellar granule cells.
AB  - The regulation and expression of muscarinic acetylcholine receptor (mAChR) mRNA
      was studied in cultured cerebellar granule cells using Northern blot
      hybridization, mRNA species for m2- and m3-mAChRs but not m1- and m4-mAChRs were
      detected in these cells. The expression of mRNAs of both m2- and m3-mAChRs
      reached a maximum on the tenth day in culture but their expression patterns
      differed. Treatment of cerebellar granule cells after 8 days in culture with 100
      microM carbachol led to differential down-regulation of the mRNA species of both
      mAChR subtypes present. Muscarinic receptor antagonists, atropine (1 microM) and
      pirenzepine (10 microM), prevented carbachol-induced m3-mAChR mRNA down
      regulation observed at 8 h. However, exposure to either atropine or pirenzepine
      alone for 8 h led to a significant up-regulation of m3-mAChR mRNA. Thus, the mRNA
      species for both m2- and m3-mAChR subtypes are differentially expressed in
      culture and down-regulated by agonist stimulation. The loss of these mRNA species
      may play a role in the down-regulation of mAChR binding sites that occurs after
      desensitization.

PMID- 1988566
TI  - Two forms of the gamma-aminobutyric acid synthetic enzyme glutamate decarboxylase
      have distinct intraneuronal distributions and cofactor interactions.
AB  - Glutamate decarboxylase (GAD) catalyzes the production of gamma-aminobutyric acid
      (GABA), a major inhibitory neurotransmitter. The mammalian brain contains two
      forms of GAD, with Mrs of 67,000 and 65,000 (GAD67 and GAD65). Using a new
      antiserum specific for GAD67 and a monoclonal antibody specific for GAD65, we
      show that the two forms of GAD differ in their intraneuronal distributions: GAD67
      is widely distributed throughout the neuron, whereas GAD65 lies primarily in axon
      terminals. In brain extracts, almost all GAD67 is in an active holoenzyme form,
      saturated with its cofactor, pyridoxal phosphate. In contrast, only about half of
      GAD65 (which is found in synaptic terminals) exists as active holoenzyme. We
      suggest that the relative levels of apo-GAD65 and holo-GAD65 in synaptic
      terminals may couple GABA production to neuronal activity.

PMID- 1988567
TI  - Intraperitoneal therapy in ovarian cancer: time's up.

PMID- 1988568
TI  - Making cocktails versus making soup.

PMID- 1988570
TI  - Treatment of advanced-stage massive mediastinal Hodgkin's disease: the case for
      combined modality treatment.
AB  - In the initial series of 198 patients treated at the National Cancer Institute
      (NCI) with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP)
      chemotherapy for Hodgkin's disease, a review of presenting chest radiographs
      available on 192 of these patients showed 49 patients with mediastinal masses
      greater than one third the greatest posteroanterior chest diameter. Five patients
      had stage IIB disease, and 44 had stage III or IV disease. Thirty-five (71%)
      patients achieved a complete remission with MOPP chemotherapy. Fourteen (40%) of
      the complete responders relapsed, but four of these achieved durable remissions
      in response to subsequent therapy. Thirty (61%) patients have died (14 induction
      failures, nine relapsed patients, seven complete responders in remission). Thus,
      with a median follow-up of 20 years (range, 15 to 23), the overall survival for
      the group is 39%, and the disease-free survival for the complete responders is
      60%. A subset of 10 patients received mantle radiation therapy after maximal
      response to MOPP. One of these patients failed to achieve complete remission, but
      among the nine complete responders only one has relapsed. In contrast, 13 of 26
      (50%) patients achieving a complete response to MOPP alone have relapsed (P2 =
      .0536). Although MOPP alone was not prospectively compared with MOPP plus
      radiation therapy in the treatment of advanced-stage massive mediastinal
      Hodgkin's disease in this series, the retrospective analysis shows a nearly
      significant difference in disease-free survival favoring combined modality
      treatment. The difference in tumor mortality between MOPP-treated (44%) and
      combined modality-treated patients (80%) was also nearly significant (P2 = .055).
      However, overall survival differences between patients treated with MOPP alone
      and those treated with combined modality therapy were not significantly different
      (P2 = 0.23) because of the mortality related to late complications of combined
      modality treatment.

PMID- 1988569
TI  - Intraperitoneal cisplatin and cytarabine in the treatment of refractory or
      recurrent ovarian carcinoma.
AB  - Preclinical evaluation has suggested impressive concentration-dependent cytotoxic
      synergy between cisplatin and cytarabine in ovarian carcinoma. To further
      evaluate the clinical relevance of these observations, 39 patients with
      refractory or recurrent ovarian carcinoma were entered onto a phase II trial of
      intraperitoneal (IP) cisplatin (100 to 105 mg/m2 per course) plus cytarabine (600
      to 900 mg per course). Treatment was administered over 2 or 3 days for a maximum
      of five monthly courses, followed by surgical reevaluation in patients without
      clinical evidence of disease. The 3-day regimen was discontinued secondary to the
      development of severe thrombocytopenia (five of 12 courses platelets decreased to
      less than 50,000/mm3). Additional toxicities included abdominal pain (moderate to
      severe at some time during therapy in 46% of patients), fever without evidence of
      infection (44%), and bacterial peritonitis (10%). Three patients declined
      surgical reassessment. Fourteen of 36 (39%; 95% confidence interval [CI], 23% to
      55%) assessable patients demonstrated surgically defined responses, including 12
      of 23 (52%; 95% CI, 32% to 72%) patients with tumor nodules less than 1 cm in
      diameter and only two of 13 (15%; 95% CI, 0% to 34%) patients with any lesion
      greater than 1 cm. There were seven (30%; 95% CI, 11% to 49%) surgically defined
      complete responses (CRs) in patients with less than 1 cm disease and none in
      patients with larger tumor nodules. IP cisplatin/cytarabine results in a high
      surgically defined response rate in patients with minimal residual ovarian
      carcinoma, but activity is low in patients with bulky intraabdominal disease.

PMID- 1988571
TI  - Discordant bone marrow involvement in diffuse large-cell lymphoma: a distinct
      clinical-pathologic entity associated with a continuous risk of relapse.
AB  - From 1975 to 1988, 50 patients with lymph node biopsy-documented diffuse large
      cell lymphoma (DLCL) presented with bone marrow involvement. Twenty-four patients
      (48%) had large-cell lymphoma (LCL) in the bone marrow and were compared with 19
      (38%) patients who had small cleaved-cell lymphoma (SCCL) in the marrow.
      Additionally, seven patients (14%) had mixed small- and large-cell lymphoma (ML)
      in the marrow. Patients who had LCL marrow involvement were younger (P less than
      .02) and more frequently had elevated lactic dehydrogenase (LDH) levels (P less
      than .001), high tumor burden (P less than .01), and more sites of extranodal
      disease (P less than .05) than those with SCCL in the marrow. The complete
      response (CR) rate to multiagent chemotherapy was 16.7% in the LCL group and
      89.4% in the SCCL group (P less than .001). One third of the patients with LCL in
      the marrow developed CNS involvement, compared with only one patient in the SCCL
      group (P = .06). Overall 5-year survival was 79% in patients with SCCL marrow
      involvement, compared with only 12% in patients with LCL in the marrow (P =
      .002). Despite a high CR rate, patients with marrow involved by SCCL were at a
      high continuous risk of relapse with only a 30% failure-free survival at 5 years.
      We conclude that bone marrow involvement with LCL predicts for extremely poor
      prognosis with low response rate and short survival. Patients with SCCL in the
      bone marrow have a high rate of CR and a high rate of 5-year survival; however,
      there is a high risk of late relapse, and only 15% are in a continuous remission
      at 8 years.

PMID- 1988572
TI  - Pentostatin induces durable remissions in hairy cell leukemia.
AB  - Fifty patients with hairy cell leukemia were treated with pentostatin (2'
      deoxycoformycin; dCF) for a median of 3 months; 32 (64%) patients achieved
      complete remission (CR), and 10 (20%) patients achieved partial remission (PR),
      for an overall response rate of 84%. After reaching maximal response, no
      maintenance therapy was administered. The median duration of follow-up is now 39
      months, and only four of 32 patients in CR and two of 10 patients in PR have
      relapsed. dCF therapy produces durable long-term, disease-free survival in
      patients with hairy cell leukemia.

PMID- 1988573
TI  - A comparison of induction and maintenance therapy for acute nonlymphocytic
      leukemia in childhood: results of a Pediatric Oncology Group study.
AB  - Two hundred fifty-six children with previously untreated acute nonlymphocytic
      leukemia (ANLL) were evaluated on a Pediatric Oncology Group (POG) phase III
      randomized trial of both induction and continuation chemotherapies. Induction
      therapy compared vincristine, cytarabine, and dexamethasone (VADx) with
      daunorubicin, cytarabine, and thioguanine (DAT). The complete remission (CR) rate
      using DAT was superior (82% v 61%, P = .02). Postremission therapy consisted of
      either "standard" two-cycle therapy or a more intensive four-cycle regimen given
      for 2 years. Overall, there was no difference in outcome for patients randomized
      to either continuation regimen. The overall complete continuous remission rate
      (CCR) for the "best" induction/continuation therapy combination at 2 years was
      .50 (SE = .06), at 3 years was .35 (.04), and at 4 years was .34 (.05). Analysis
      of selected clinical and laboratory parameters demonstrated differences in
      induction responses favoring DAT induction but did not impact eventual disease
      free survival. There were two subgroups of patients who responded better to four
      cycle continuation therapy. These were patients with French-American-British
      (FAB) M1/M2 (2-year CCR was .20 v .44, P = .01) and patients older than 10 years
      at diagnosis (.32 v .62, P = .004).

PMID- 1988575
TI  - Venous and arterial thrombosis in patients who received adjuvant therapy for
      breast cancer.
AB  - The records of 2,673 patients randomized according to seven consecutive Eastern
      Cooperative Oncology Group (ECOG) studies of adjuvant therapy for breast cancer
      were reviewed for the occurrence of vascular complications. All protocols opened
      and closed between June 1977 and July 1987. The objectives of the present study
      were (1) to compare the frequency of vascular complications among patients who
      received adjuvant therapy for breast cancer with patients on observation, and (2)
      to estimate the contribution of chemotherapy and hormonal therapy to the
      occurrence of venous and arterial thrombi. The frequency of thrombosis, both
      venous and arterial combined, was 5.4% among patients who received adjuvant
      therapy and was 1.6% among patients on observation (P = .0002). Premenopausal
      patients who received chemotherapy and tamoxifen had significantly more venous
      complications than those who received chemotherapy without tamoxifen (2.8% v
      0.8%, P = .03). Postmenopausal patients who received tamoxifen and chemotherapy
      had significantly more venous thrombi than those who received tamoxifen alone
      (8.0% v 2.3%, P = .03) or those who were observed (8.0% v 0.4%, P less than
      .0001). Premenopausal patients who received tamoxifen and chemotherapy had a 1.6%
      frequency of arterial thrombosis, significantly more than patients who received
      chemotherapy alone (1.6% v 0.0%, P = .004). The frequency of arterial thrombosis
      among postmenopausal patients was not significantly correlated with adjuvant
      therapy. In conclusion, patients who received adjuvant therapy for breast cancer
      had a 5.4% frequency of thromboembolic complications, significantly more than
      those who were observed. The combination of chemotherapy and tamoxifen was
      associated with more venous and arterial thromboembolic complications than
      chemotherapy alone in premenopausal patients and with more venous thrombi than
      tamoxifen alone among postmenopausal patients.

PMID- 1988574
TI  - Influence of chemotherapy administration on monocyte activation by liposomal
      muramyl tripeptide phosphatidylethanolamine in children with osteosarcoma.
AB  - The purpose of these studies was to determine whether chemotherapy interfered
      with the ability of peripheral blood monocytes from patients with osteosarcoma to
      respond to the liposome-encapsulated activating agent muramyl tripeptide
      phosphatidylethanolamine (L-MTP-PE). This was done in preparation of designing an
      adjuvant therapy protocol that includes L-MTP-PE combined with chemotherapy
      postoperatively for the treatment of primary osteosarcoma. The majority of
      patients who fail current adjuvant chemotherapy do so while on chemotherapy.
      Therefore, we believe it is important to combine L-MTP-PE with chemotherapy early
      in the treatment course rather than waiting until all chemotherapy cycles are
      completed. The tumoricidal properties of monocytes from patients with
      osteosarcoma could be activated by L-MTP-PE to levels equal to or greater than
      those expressed by normal control monocytes. No intrinsic monocyte defect could
      be demonstrated. Single-agent chemotherapy consisting of cisplatin (CPD), high
      dose methotrexate (MTX), Cytoxan (CTX, cyclophosphamide; Bristol-Myers Co,
      Evansville, IN), or Adriamycin (ADR, doxorubicin; Adria Laboratories, Columbus,
      OH) did not interfere with this activation process. There was even a suggestion
      of enhanced activation potential following the administration of ADR. However,
      when both ADR and CTX were administered together on the same day, profound
      suppression in monocyte activation was observed. This suppressed function
      returned to normal by 3 weeks postcombination therapy. We therefore conclude that
      L-MTP-PE can be combined with ADR, CPD, MTX, or CTX as single agents but
      recommend that ADR plus L-MTP-PE is the most effective combination. By contrast,
      we discourage the use of L-MTP-PE when ADR and CTX are given together.

PMID- 1988576
TI  - Epirubicin at two dose levels with prednisolone as treatment for advanced breast
      cancer: the results of a randomized trial.
AB  - Two hundred eleven patients with advanced breast cancer were randomized to
      receive either epirubicin (E) 50 mg/m2 and prednisolone (LEP) or E 100 mg/m2 and
      prednisolone (HEP). The intended treatment consisted of 16 courses of LEP or
      eight courses of HEP given at 3-weekly intervals. Reasons for stopping treatment
      early included progressive disease, stable disease without symptomatic
      improvement, or severe toxicity deemed intolerable by either the patient or
      physician. Toxicity was recorded at 3-weekly and response at 9-weekly intervals
      using the World Health Organization (WHO) criteria of response and toxicity. Two
      hundred nine patients were eligible for analysis, 98% of whom have been followed
      for more than a year. One hundred four patients received LEP and 105 HEP.
      Significantly worse myelosuppression, alopecia, nausea and vomiting, and
      mucositis were seen in the high-dose arm (P less than or equal to .001). More
      patients in the LEP arm stopped treatment before the fourth course than in the
      HEP arm, and the commonest reason for stopping was progressive disease. A similar
      median number of courses was given in each arm. There was a significantly higher
      response in the HEP arm (HEP - complete response [CR] + partial response [PR] =
      41%, LEP - CR + PR = 23%). Despite this, no statistically significant differences
      was seen in overall survival or progression-free interval. The median survival
      for HEP and LEP was 44 and 46 weeks, respectively.

PMID- 1988577
TI  - A prospective randomized trial comparing epirubicin monochemotherapy to two
      fluorouracil, cyclophosphamide, and epirubicin regimens differing in epirubicin
      dose in advanced breast cancer patients. The French Epirubicin Study Group.
AB  - The French Epirubicin Study Group carried out a randomized trial comparing
      epirubicin alone 75 mg/m2 with fluorouracil (5FU) 500 mg/m2, cyclophosphamide 500
      mg/m2, and epirubicin 50 mg/m2 (FEC 50) and 5FU 500 mg/m2, cyclophosphamide 500
      mg/m2, and epirubicin 75 mg/m2 (FEC 75) as first treatment for advanced breast
      cancer patients. Patients were stratified according to whether or not there were
      bone metastases only. Four hundred twelve patients entered this trial; 378 were
      assessable for tolerability and 365 for efficacy. The overall response rates were
      comparable between FEC 50 (44.6%) and FEC 75 (44.7%), but both were better than
      the epirubicin alone (30.6%) (P = .04 and P = .0006, respectively). The complete
      response rate was better in FEC 75 (15.5%) than in FEC 50 (7%) (P = .025) or
      epirubicin (4%) (P = .002). Similar results were obtained in the group of
      patients without bone-only metastases. No difference in the three treatments was
      observed in the patients with bone metastases only. Mean durations of response
      were similar in the three groups, being 412 days, 440 days, and 350 days for FEC
      50, FEC 75, and epirubicin, respectively. Patients without previous adjuvant
      chemotherapy fared better than those with previous treatment (without
      anthracyclines). Tolerability was fair in the three groups. Overall, the
      epirubicin-alone group showed better tolerance than the two other groups, which
      did not differ significantly. Time to progression and survival were not different
      among the three groups, but more early relapses occurred in the epirubicin and
      FEC 50 groups; survival seemed to be better during the first 8 months in the FEC
      75 group, and the survival difference between the epirubicin group and the FEC 75
      group was of borderline significance. No difference in survival was observed
      between epirubicin- and FEC 50-group patients, even though the response rate was
      significantly worse in the monochemotherapy group.

PMID- 1988578
TI  - Intrapleural cisplatin and cytarabine in the management of malignant pleural
      effusions: a Lung Cancer Study Group trial.
AB  - Malignant pleural effusions are a common and significant problem in patients with
      advanced malignancies. Pleurodesis with tetracycline or other sclerosing agents
      is the usual treatment for malignant pleural effusions. In contrast to this
      approach, intrapleural chemotherapy has the potential advantage of treating the
      underlying malignancy in addition to controlling the effusion. Intracavitary
      cisplatin-based chemotherapy, which is cytotoxic rather than sclerosing, has
      proven safe and effective via the intraperitoneal route in ovarian cancer and
      malignant mesothelioma. There has been little previous experience, however, with
      intrapleural cisplatin-based chemotherapy. As part of a planned series of trials
      in malignant mesothelioma, the Lung Cancer Study Group first evaluated
      intrapleural cisplatin and cytarabine in patients with malignant pleural
      effusions from a variety of solid tumors. From April 1986 to November 1987, 46
      patients with cytologically proven, symptomatic, and previously untreated
      malignant pleural effusions were entered on study. A single dose of cisplatin 100
      mg/m2 plus cytarabine 1,200 mg was instilled into the pleural space via a chest
      tube, which was then immediately removed. Patients were evaluated for toxicity
      and response at 24 hours; 1, 2, and 3 weeks; and then monthly. No recurrence of
      the effusion was considered a complete response (CR). Partial response (PR) was
      defined as a 75% or greater decrease in the amount of the effusion on serial
      chest radiographs. One patient experienced reversible grade 4 renal toxicity,
      four patients had grade 3 hematologic toxicity, and five patients had grade 3
      cardiopulmonary toxicity. The overall response rate (CR plus PR) at 3 weeks was
      49% (18 of 37 patients). The median length of response was 9 months for a CR and
      5.1 months for a PR. The outcome of this trial was sufficiently encouraging that
      this regimen has been incorporated into subsequent trials for malignant pleural
      mesothelioma.

PMID- 1988580
TI  - Developing a postgraduate medical oncology training program in Taipei, Taiwan,
      Republic of China.
AB  - Because cancer is the number one cause of mortality in Taiwan, a governmental
      decision was made to develop an experiment in medical oncology education using a
      United States-style training program in medical oncology in three Taipei, Taiwan,
      university hospitals. In the past, trainees from developing countries came to the
      United States or other foreign countries to receive specialty training. In doing
      so, the training did not necessarily prepare the individuals with skills to treat
      the indigenous cancers, nor did they work with other related specialists or
      support staff such as nursing and pharmacy, so important to providing good cancer
      care. This program involved 13 fellows with significant laboratory experience
      working with American faculty on-site. The major benefits of this model for
      oncology training are that the trainees developed important interdisciplinary
      relationships with local staff at each of the hospitals; they were involved in
      the treatment of the major cancer diseases of Taiwan such as nasopharyngeal,
      hepatocellular, and cervical cancers as well as breast, lung, and colon cancers;
      and they completed a certification process involving written and oral tests by
      two senior American oncologist examiners. Oncology services have been established
      at each of the hospitals and most of the fellows have expressed an interest or
      made arrangements to come to the United States to get additional research
      experience.

PMID- 1988579
TI  - Sex or survival: trade-offs between quality and quantity of life.
AB  - Patients with localized prostate cancer may be treated with either surgery
      (radical prostatectomy) or radiotherapy. Although controversial, many physicians
      believe that surgery offers a higher survival rate. However, the surgical
      treatment may also produce a higher rate of sexual impotency. Our study assessed
      how men value survival and sexual potency when asked to trade off one for the
      other. Using the treatment-choice technique, we interviewed 50 men aged 45 to 70
      years without known prostate cancer. At hypothetical rates of survival (90% at 5
      years for surgery) and impotency (90% for surgery and 40% for radiotherapy)
      representing published estimates, 32% of respondents were unwilling to trade off
      any survival, but 68% were willing to trade off a 10% or greater advantage in 5
      year survival (by choosing radiotherapy) to maintain sexual potency. The median 5
      year survival traded off was 10% (range, 0% to 80%). Willingness to trade off
      survival for sexual potency was significantly related to level of education, but
      not to age, interest in sex, frequency of sexual intercourse, or ability to
      achieve erection. We conclude that some men may choose treatment with lower long
      term survival to increase their chance of remaining sexually potent. Because
      these men may be difficult to identify in clinical practice, physicians should
      thoroughly discuss both surgery and radiotherapy options with patients who have
      localized prostate cancer.

PMID- 1988581
TI  - When is a prognostic factor useful? A guide for the perplexed.
AB  - Traditionally, a number of variables have been used to predict outcome in
      patients with early-stage breast cancer. These tests are simple to perform and
      relatively inexpensive. Recently, a number of new factors, eg, tumor
      proliferative index, nuclear DNA content, and amplification or overexpression of
      growth-promoting genes or oncogenes have been identified as potential predictors
      of outcome in patients with breast cancer. There is now increasing pressure to
      introduce such tests into routine clinical practice. How does a clinical
      practitioner identify which test, or group of tests, best predicts adverse
      outcome and whether any more clinically useful information is provided than with
      the use of more traditional factors alone? The aim of a prognostic test in breast
      cancer is to predict which patients are destined to develop a recurrence of
      cancer and those who are not. The prognostic usefulness of a test can be
      expressed in terms of relative risk (RR), which is the ratio of the risk of
      breast cancer recurrence in patients who test positive to the risk in those who
      test negative. Methodologic guidelines that should be satisfied by a study
      evaluating the predictive ability of a test include the following: (1) Was an
      inception cohort assembled? (2) Was the referral pattern described? (3) Were
      laboratory and clinical outcomes assessed in a blinded fashion? (4) Was complete
      follow-up achieved? (5) Was adjustment for extraneous prognostic factors carried
      out? (6) Were appropriate statistical methods used? An approach is suggested to
      help the clinician choose the test, or combination of tests, likely to
      discriminate between "high-" and "low-risk" patients in his/her own practice. The
      decision regarding what particular threshold value (risk) defined by a prognostic
      test (or series of tests) warrants adjuvant therapy for an individual patient is
      a complex one but should be based on a clear presentation of the risks and
      benefits to the patient.

PMID- 1988582
TI  - CA125 and malignant lymphomas.

PMID- 1988583
TI  - Central corpectomy for cervical spondylotic myelopathy: a consecutive series with
      long-term follow-up evaluation.
AB  - Since 1984, a consecutive series of patients with cervical spondylotic myelopathy
      has been treated by central corpectomy and strut grafting. This report focuses on
      40 cases operated on between 1984 and 1987 and followed from 2 to 5 years. The
      perioperative complication rate was 47.5%, with a 7.5% incidence of persistent
      sequelae: severe C-5 radiculopathy in one patient, swallowing dysfunction in one,
      and hypoglossal nerve palsy in one. No single factor (age, duration of symptoms,
      or severity of myelopathy) was absolutely predictive of outcome; however,
      syndromes of short duration had the best likelihood of cure. Similar outcomes
      were associated, individually, with long duration of symptoms, age over 70 years,
      and severe myelopathy. After factoring a 5% regression of improvement, the long
      term cure rate was 57.5% and the failure rate was 15%. Myelopathy worsening was
      not documented.

PMID- 1988584
TI  - Coaptation of the anterior rami of C-3 and C-4 to the upper trunk of the brachial
      plexus for cervical nerve root avulsion.
AB  - No surgical procedure has been available to repair cervical nerve root avulsion
      inside the spinal canal. Results with peripheral neurotization of denervated
      muscles have been discouraging. The authors have performed bridge-graft
      coaptation in three patients with C-5 and C-6 nerve root avulsion. The components
      of the coaptation included the anterior primary rami of C-3 and C-4 as the donor
      material, the entire upper trunk as the recipient, and the sural nerve graft as
      the bridge. This procedure resulted in restoration of motor function in the
      biceps and shoulder-girdle muscles and produced improved sensation. Stimulation
      of the C-3 and C-4 nerve roots elicited electrical responses in the biceps and
      deltoid muscles that indicated nerve growth through the graft and the brachial
      plexus into these muscles. This reconstructive procedure is effective and should
      stimulate development of new approaches to treatment of cervical nerve root
      avulsion and proximal brachial plexopathy.

PMID- 1988585
TI  - Cerebral palsy and rhizotomy. A 3-year follow-up evaluation with gait analysis.
AB  - A recent increase in the popularity of selective rhizotomy for reduction of
      spasticity in cerebral palsy has led to a demand for more objective studies of
      outcome and long-term follow-up results. The authors present the results of gait
      analysis on 14 children with spastic cerebral palsy, who underwent selective
      posterior rhizotomy in 1985. Sagittal plane gait patterns were studied before
      surgery and at 1 and 3 years after surgery using a digital camera system. The
      parameters measured included the range of motion at the knee and thigh, stride
      length, speed of walking, and cadence. The range of motion at the knee was
      significantly increased at 1 year after surgery and further improved to a nearly
      normal range at 3 years after surgery. In contrast, postoperative measurements of
      thigh range exceeded normal values at 1 year, but decreased toward normal range
      at 3 years. While improvements in range of motion continued between Years 1 and
      3, the children developed a more extended thigh and knee position, which
      indicated a more upright walking posture. Stride length and speed of walking also
      improved, while cadence remained essentially unchanged. This 3-year follow-up
      study, the first to examine rhizotomy using an objective approach, has provided
      some encouraging results regarding early functional outcome.

PMID- 1988586
TI  - Use of MR imaging-compatible Halifax interlaminar clamps for posterior cervical
      fusion.
AB  - Twenty-one patients requiring posterior cervical fusion were treated with
      magnetic resonance (MR) imaging-compatible Halifax interlaminar clamps for
      internal fixation. Various levels were involved: the C1-2 level in eight cases,
      the C4-5 level in four, the C5-6 level in three, the C6-7 level in three, the C4
      6 level in two, and the C5-7 level in one. Bilateral clamps were used in 18 cases
      and unilateral clamps in three. Autogenous iliac bone grafting was performed in
      all cases but one. Follow-up periods ranged from 1 to 18 months (average 9.2
      months), with no complications or mechanical failures occurring thus far. Follow
      up diagnostic studies revealed rigid fixation and fusion in all cases. The MR
      imaging-compatibility of the clamps allowed excellent follow-up studies with
      minimal artifact. Because of their ease of use, rigid stabilization, good
      results, lack of complications, and compatibility with MR imaging, the Halifax
      interlaminar clamp with bone grafting provides an ideal method for posterior
      cervical stabilization.

PMID- 1988587
TI  - The interspinous method of posterior atlantoaxial arthrodesis.
AB  - Thirty-six patients underwent C1-2 posterior wiring and fusion procedures over a
      5-year period for unstable C-2 fractures (eight cases), unstable atlas-axis
      combination fractures (six cases), rheumatoid C1-2 instability (14 cases), os
      odontoideum (four cases), traumatic C1-2 ligamentous instability (three cases),
      or instability secondary to a C-2 tumor (one case). In each case, the
      atlantoaxial arthrodesis utilized sublaminar wire at C-1 and incorporated an
      iliac-crest strut-graft positioned between the posterior arches of C-1 and C-2,
      held in place by securing wire around the base of the spinous process of the
      axis. Follow-up examination was performed in all patients after a mean
      postoperative duration of 33.7 months. The technical aspects and clinical merits
      of this fusion procedure, which led to a 97% union rate (one nonunion) and
      minimal morbidity and mortality rates, are presented.

PMID- 1988588
TI  - A variant of arteriovenous fistulas within the wall of dural sinuses. Results of
      combined surgical and endovascular therapy.
AB  - Dural arteriovenous (AV) fistulas are thought to be acquired lesions that form in
      an area of thrombosis within a sinus. If the sinus remains completely thrombosed,
      venous drainage from these lesions occurs through cortical veins, or, if the
      sinus is open, venous drainage is usually into the involved sinus. Among 105
      patients with dural AV fistulas evaluated over the the past 5 years, seven had a
      unique type of dural AV fistula in the superior sagittal, transverse, or straight
      sinus in which only cortical venous drainage occurred despite a patent involved
      sinus; the fistula was located within the wall of a patent dural sinus, but
      outflow was not into the involved sinus. This variant of dural AV fistulas puts
      the patient at serious risk for hemorrhage or neurological dysfunction caused by
      venous hypertension. Three patients presented with hemorrhage, one with
      progressive neurological dysfunction, one with seizures, and two with bruit and
      headaches. A combination of surgical and endovascular techniques was used to
      close the fistula while preserving flow through the sinus.

PMID- 1988589
TI  - Management of hemorrhagic complications from preoperative embolization of
      arteriovenous malformations.
AB  - Endovascular embolization procedures have undergone dramatic evolution and
      improvement in recent years. Despite these advances, controversy remains
      regarding the optimal role of these procedures in treating cerebral arteriovenous
      malformations (AVM's) and whether their purpose should be as a presurgical
      adjunct or as primary therapy. This controversy risks fragmentation between
      disciplines in the broader efforts to improve management of cerebrovascular
      disorders. The authors report seven cases of life-threatening hemorrhages that
      occurred during staged invasive therapy for AVM's which illustrate the value of a
      unified team approach to optimize patient care. Each patient underwent at least
      one embolization procedure using polyvinyl alcohol particles, followed in two
      cases by the occlusion of proximal feeding vessels by platinum microcoils and in
      one case by the attempted detachment of an endovascular balloon. In three
      patients, catheter penetration into the subarachnoid space resulted in
      subarachnoid hemorrhage. One patient suffered rupture of a large feeding vessel
      during balloon inflation. The final three patients sustained intracranial
      hemorrhage 2 hours, 8 hours, and 5 days, respectively, following embolization.
      All but two patients underwent emergency craniotomy at the time of the
      complication. These cases underscore the advantages of interdisciplinary
      management optimizing decision-making and providing expeditious care when life
      threatening complications develop.

PMID- 1988590
TI  - Acute subdural hematoma: morbidity, mortality, and operative timing.
AB  - Traumatic acute subdural hematoma remains one of the most lethal of all head
      injuries. Since 1981, it has been strongly held that the critical factor in
      overall outcome from acute subdural hematoma is timing of operative intervention
      for clot removal; those operated on within 4 hours of injury may have mortality
      rates as low as 30% with functional survival rates as high as 65%. Data were
      reviewed for 1150 severely head-injured patients (Glasgow Coma Scale (GCS) scores
      3 to 7) treated at a Level 1 trauma center between 1982 and 1987; 101 of these
      patients had acute subdural hematoma. Standard treatment protocol included
      aggressive prehospital resuscitation measures, rapid operative intervention, and
      aggressive postoperative control of intracranial pressure (ICP). The overall
      mortality rate was 66%, and 19% had functional recovery. The following variables
      statistically correlated (p less than 0.05) with outcome; motorcycle accident as
      a mechanism of injury, age over 65 years, admission GCS score of 3 or 4, and
      postoperative ICP greater than 45 mm Hg. The time from injury to operative
      evacuation of the acute subdural hematoma in regard to outcome morbidity and
      mortality was not statistically significant even when examined at hourly
      intervals although there were trends indicating that earlier surgery improved
      outcome. The findings of this study support the pathophysiological evidence that,
      in acute subdural hematoma, the extent of primary underlying brain injury is more
      important than the subdural clot itself in dictating outcome; therefore, the
      ability to control ICP is more critical to outcome than the absolute timing of
      subdural blood removal.

PMID- 1988591
TI  - Orbital rim and malar advancement for unilateral coronal synostosis in the older
      pediatric age group.
AB  - The authors describe a technique for lateral orbital rim and malar advancement in
      patients in the older pediatric age group. The technique makes use of a strip
      craniotomy containing the supraorbital margin, greater sphenoid wing, and
      temporal bone, with en bloc inclusion of the lateral orbital rim, zygoma, and
      malar prominence. The method allows a contoured yet stable construction secured
      in a tongue-in-groove fashion with plate-and-screw fixation. It creates a
      symmetrical reconstruction of both frontal and lateral orbital aspects in the
      untreated or inadequately treated older plagiocephalic child with orbital
      dystopia. The accompanying malar recession is likewise corrected.

PMID- 1988592
TI  - Endoscopic ventricular fenestration using a "saline torch".
AB  - The fiberoptic endoscope has never gained popularity among neurosurgeons although
      it is ideally suited for navigating within the cerebral ventricles. Recent
      advances in optics and miniaturization make the application of endoscopy in
      neurosurgery more practical. The authors report eight children who underwent
      ventriculoscopic fenestration of symptomatic loculated cerebrospinal fluid (CSF)
      collections. These CSF collections were either isolated ventricular cysts or
      trapped lateral ventricles secondary to obstruction at the foramen of Monro. Cyst
      wall dissection was carried out with a "saline torch" dissector which was
      introduced through a working channel in the ventriculoscope. The torch was used
      to coagulate vessels and to sculpt large windows in cyst walls or in the septum
      pellucidum. Ventriculoscope-guided cyst fenestration can be performed safely and
      easily under direct vision. The technique may permit simplification of shunt
      systems in some patients and elimination of shunts in others.

PMID- 1988593
TI  - Intracranial arachnoid cysts in children. A comparison of the effects of
      fenestration and shunting.
AB  - The best operative intervention for children with arachnoid cysts remains the
      subject of controversy. Recent reports stress that craniotomy for cyst
      fenestration is associated with a low incidence of morbidity and mortality and
      may leave the child shunt-independent. The cases of 40 pediatric patients with
      arachnoid cysts treated between 1978 and 1989 are reported. Five children with
      mild symptoms and small cysts that remained stable on follow-up studies have not
      required surgical intervention. Of 15 patients with cysts initially treated by
      fenestration, 10 (67%) showed no clinical or radiographic improvement
      postoperatively and have undergone cyst-peritoneal (eight patients) or
      ventriculoperitoneal (VP) shunting (one patient), or revision of a VP shunt
      placed for hydrocephalus before cyst fenestration (one patient). Two other
      patients with existing VP shunts required no further procedures. Thus, only three
      (20%) of 15 patients initially treated by fenestration remain shunt-independent
      after a median follow-up period of 8 years. The 20 other patients were initially
      treated by cysts shunting and all improved postoperatively; shunt revision has
      been necessary in six (30%) of these 20 patients because of cysts recurrence.
      Cyst location influenced the success of shunt treatment; none of the seven middle
      cranial fossa cysts treated by shunting have required revision, but results with
      cysts in other locations were less favorable. In all locations, though, shunting
      was more successful than fenestration. It is concluded that cyst-peritoneal or
      cyst-VP shunting is the procedure of choice for arachnoid cysts in most
      locations, including those in the middle cranial fossa.

PMID- 1988594
TI  - Multiple adenomas of the human pituitary. A retrospective autopsy study with
      clinical implications.
AB  - In a review of autopsy material from two centers, 20 pituitary glands were found
      containing multiple adenomas. In total, 44 adenomas were identified
      histologically; 16 glands contained double tumors and in four glands triple
      adenomas were found. Size was measured in 30 tumors, all of which were
      microadenomas. Thirty-four adenomas were located in the lateral wings and 10 lay
      in the median wedge. Forty-one tumors were chromophobic and three were
      basophilic. Immunocytochemical analysis of the 44 tumors demonstrated the
      presence of prolactin in 11, adrenocorticotropic hormone in three, growth hormone
      in one, and alpha-subunit as well as follicle-stimulating hormone and luteinizing
      hormone in one. Of the 20 patients studied, there were 11 men and nine women,
      with an average age of 69 years. All patients died from various nonendocrine
      causes. With the exception of one patient who appeared mildly acromegalic, no
      correlation was observed between pituitary morphology and clinical data. This
      study found a 10.4% frequency of adenomas in pituitaries studied randomly at
      autopsy. Multiple tumors were encountered in 0.9% of cases. Despite its low
      frequency, adenoma multiplicity may underlie surgical failure in cases in which
      one adenoma is removed and the other is left behind.

PMID- 1988595
TI  - Intraoperative monitoring of the facial nerve during decompressive surgery for
      hemifacial spasm.
AB  - In 11 consecutive patients, intraoperative electromyographic (EMG) recordings
      were made from the facial muscles during microvascular decompression for
      hemifacial spasm. In one patient, recordings could not be obtained for technical
      reasons, and two patients had no abnormality. In the remaining eight patients,
      the abnormal response resolved before decompression in two, resolved immediately
      at the time of decompression in five, and failed to resolve in one. All patients
      were relieved of their hemifacial spasm. In the five patients whose abnormalities
      resolved at the time of decompression, there was a precise intraoperative
      correlation between decompression of the nerve and disappearance of the abnormal
      EMG response. In three cases, this was a useful guide to the need to decompress
      more than one vessel. These results confirm the findings of Moller and Jannetta,
      support the use of this technique for intraoperative monitoring of facial nerve
      decompression procedures, and provide strong circumstantial evidence that
      vascular cross-compression is an important etiological factor in hemifacial
      spasm.

PMID- 1988596
TI  - Cerebral blood flow patterns at major vessel bifurcations and aneurysms in rats.
AB  - Cerebral arterial bifurcations in rats were treated to induce cerebral aneurysms
      experimentally, and flow patterns of latex particles introduced under a constant
      flow rate were analyzed with a 16-mm cine-camera and videocassette recorder.
      Cerebral aneurysms were produced by ligating one common carotid artery, inducing
      experimental hypertension, and feeding the animals beta-aminopropionitrile. After
      perfusion and fixation, samples of cerebral arterial bifurcations with shallow
      invaginations and with small aneurysms were obtained and used for analysis.
      Bifurcations in rats without experimental treatment were used as control
      specimens. Flow studies in the control bifurcations showed that the apical
      intimal pad, not the apex itself, acted as the flow divider. Small particles
      tended to accumulate at the region just distal to the apical intimal pad, where
      the initial aneurysmal changes are known to occur. This indicates stagnation of
      flow at that site. In the bifurcations with shallow invaginations and small
      aneurysms, a marked pressure gradient was present at the proximal end of the
      aneurysm orifice. A tendency for stagnation of small particles near the aneurysm
      wall was also observed. The wall shear stress was highest at the distal end of
      the aneurysmal orifice, which may be responsible for the development of these
      lesions.

PMID- 1988598
TI  - Evaluation of brain-stem dysfunction following severe fluid-percussion head
      injury to the cat.
AB  - The degree of brain-stem dysfunction associated with high-level fluid-percussion
      injury (3.0 to 3.8 atm) was investigated in anesthetized cats. Measurements were
      made of the animals' intracranial pressure (ICP) pressure-volume index (PVI), far
      field brain-stem auditory evoked responses (BAER's), and cerebral blood flow
      (CBF). The animals were classified into two groups based on the severity of
      neuropathological damage to the brain stem after trauma: Group 1 had mild
      intraparenchymal and subarachnoid hemorrhages and Group 2 had severe
      intraparenchymal and subarachnoid hemorrhages. The ICP values in Group 1 were
      insignificantly lower than those in Group 2, while the PVI values in Group 2 were
      clearly lower (p less than 0.05). Immediately after the injury, peaks II, III,
      and IV of the BAER's demonstrated a transitory and marked suppression. One Group
      1 and two Group 2 animals showed the disappearance of peak V. In Group 1, the
      latencies of peak II, III, and IV gradually increased until 60 to 150 minutes
      postinjury, then returned to 95% of baseline value at 8 hours; however, the
      animals in Group 2 showed poor recovery of latencies. Two hours after brain
      injury, the CBF decreased to 40% of the preinjury measurement in both groups (p
      less than 0.001). In contrast to Group 2, the CBF in Group 1 returned to 86.8% of
      the preinjury measurement by 8 hours following the injury. Changes in PVI, BAER,
      and CBF correlated well with the degree of brain-stem injury following severe
      head injury. These data indicate that high-level fluid-percussion injury (greater
      than 3.0 atm) is predominantly a model of brain-stem injury.

PMID- 1988597
TI  - The effects of etomidate on cerebral metabolism and blood flow in a canine model
      for hypoperfusion.
AB  - The effects of etomidate, a nonbarbiturate cerebral metabolic depressant, on
      cerebral metabolism and blood flow were studied in 29 dogs during cerebral
      hypoperfusion. Three groups of animals were studied during a 45-minute
      normotensive and a 30-minute hypotensive period: 10 control animals without
      etomidate, 11 animals receiving a 0.1-mg/kg etomidate bolus followed by an
      infusion of 0.05 mg/kg/min etomidate (low-dose group), and eight animals
      receiving doses of etomidate sufficient to suppress electroencephalographic
      bursts (high-dose group). The mean arterial pressure fell to similar levels (p
      less than 0.05) during hypotension in all three groups (40 +/- 5, 38 +/- 3, and
      27 +/- 6 mm Hg, respectively). The mean cerebral oxygen extraction fraction rose
      (p less than 0.05) from 0.23 +/- 0.02 to 0.55 +/- 0.08 in the five control
      animals tested and from 0.33 +/- 0.02 to 0.53 +/- 0.02 in the seven animals
      tested in the low-dose group, but did not increase (p greater than 0.05) in the
      four animals tested in the high-dose group (0.24 +/- 0.03 to 0.23 +/- 0.05). Mean
      cerebral blood flow levels decreased in all groups during hypotension (p less
      than 0.05): 42 +/- 3 to 21 +/- 4 ml/100 gm/min (52% +/- 12% decrease) in the five
      animals tested in the control group, 60 +/- 8 to 24 +/- 6 ml/100 gm/min (56% +/-
      13% decrease) in the four animals tested in the low-dose group, and 55 +/- 8 to
      22 +/- 3 ml/100 gm/min (60% +/- 4% decrease) in the four animals tested in the
      high-dose group. In summary, the cerebral oxygen extraction fraction increased in
      the control animals and low-dose recipients during hypotension, suggesting the
      presence of threatened cerebral tissue. In contrast, the cerebral oxygen
      extraction did not change during hypotension when high-dose etomidate was
      administered. It is concluded that high-dose etomidate may preserve the cerebral
      metabolic state during hypotension in the present model.

PMID- 1988599
TI  - An epithelial cyst in the cerebellopontine angle. Case report.
AB  - A case of a benign epithelial cyst in the posterior cranial fossa is described.
      It had the unique histological feature of a double-layered cuboidal epithelial
      lining. Detailed immunohistochemical and electron microscopic studies supported
      an endodermal origin. The differential diagnosis and the histogenesis of
      epithelial cysts in the central nervous system are discussed.

PMID- 1988600
TI  - Spontaneous decompression of syringomyelia: magnetic resonance imaging findings.
      Case report.
AB  - The case of a 30-year-old woman with Chiari I malformation and a cervicothoracic
      syrinx is presented. The patient was followed clinically over a 2 1/2-year
      period. Spontaneous and complete resolution of the syrinx, as documented by
      serial magnetic resonance studies, was accompanied by only a minimal change in
      objective symptomatology.

PMID- 1988601
TI  - Abnormal origin of bilateral ophthalmic arteries. Case report.
AB  - The case of a 64-year-old woman with multiple intracranial aneurysms and abnormal
      ophthalmic arteries arising from the bifurcation of the internal carotid artery
      is described. It is believed that this type of anomaly of the ophthalmic artery
      has not previously been reported. The neuroradiological and operative findings of
      this case are presented.

PMID- 1988602
TI  - Familial hemifacial spasm associated with arterial compression of the facial
      nerve. Case report.
AB  - This report of an 88-year-old woman with familial hemifacial spasm includes the
      first published postmortem description of hemifacial spasm with cross-compression
      of the seventh cranial nerve root exit zone by a redundant loop of the anterior
      inferior cerebellar artery and associated vascular plexus. Histological
      examination of the seventh and eighth cranial nerve complex suggested nerve
      degeneration because increased numbers of corpora amylacea were present just
      distal to the compression concavity. There was no evidence of demyelination or
      gliosis of the nerve. This case suggests that vascular compression of the nerve
      root exit zone is an important condition in the etiology of most of these cases.
      This is the third reported case of familial hemifacial spasm; to date, all such
      patients have had left facial involvement. The family pedigree in this case
      suggests a pattern of autosomal-dominant inheritance with partial penetrance. The
      genetic basis for familial hemifacial spasm may involve anatomical variants or
      anomalies of the posterior circulation, since both posterior inferior cerebellar
      arteries were congenitally absent in this case.

PMID- 1988603
TI  - Accessory arm--dysraphism or disparity? Case report.
AB  - The case of a 3-month-old infant with an accessory third arm is reported. The
      extra appendage was attached at the midcervical region and was associated with
      posterior cervical dysraphism and a cervical cord lipoma. Possible theories of
      origin are examined.

PMID- 1988604
TI  - Treatment of intractable arterial hemorrhage during stereotactic brain biopsy
      with thrombin. Report of three patients.
AB  - Of 165 consecutive patients undergoing computerized tomography- or magnetic
      resonance imaging-guided stereotactic brain biopsies at the Cleveland Clinic
      between June, 1987, and November, 1989, four patients (2.4%) developed arterial
      hemorrhage refractory to conventional efforts to secure hemostasis. Craniotomy
      was performed in one of these patients to control the hemorrhage; in the other
      three, 0.5 to 2 cc of thrombin (5000 U/cc) was slowly injected via the biopsy
      cannula, resulting in immediate control of bleeding in all three cases.
      Postoperatively, the first two patients treated with 1 to 2 cc of thrombin were
      slow to awaken; one had evidence of vasospasm by transcranial Doppler ultrasound
      studies and multiple infarcts on cranial computerized tomography, while the other
      had a moderate-sized frontal hematoma with intracranial hypertension. After
      prolonged recovery periods, only mild neurological deficits persisted in both
      patients. The third patient, treated with 0.5 cc of thrombin, had an uneventful
      postoperative course. Thrombin is highly effective for stopping intractable
      arterial hemorrhage during stereotactic brain biopsy; however, it is a
      vasospastic agent and may have been responsible for the cerebral infarctions in
      one patient. Therefore, thrombin should be used only as a last resort, short of
      craniotomy, to control intractable arterial hemorrhage during stereotactic brain
      biopsy.

PMID- 1988605
TI  - A new clip applier. Technical note.

PMID- 1988606
TI  - Foundation for International Education in Neurological Surgery, Inc. Report of
      Activities, 1988-1990.

PMID- 1988607
TI  - Antibiotic effect on incidence of postcraniotomy seizures.

PMID- 1988608
TI  - Neuro-ophthalmological assessment for pituitary macroadenomas.

PMID- 1988609
TI  - Forced subarachnoid air in transsphenoidal surgery.

PMID- 1988611
TI  - Myocardial viability--what is the definition?

PMID- 1988610
TI  - Myocardial metabolism of fluorodeoxyglucose compared to cell membrane integrity
      for the potassium analogue rubidium-82 for assessing infarct size in man by PET.
AB  - Potassium loss from damaged myocardial cells is linearly related to CPK enzyme
      loss reflecting extent of necrosis. The potassium analog, rubidium-82 (82Rb), is
      extracted after i.v. injection and retained in viable myocardium but is not
      trapped or washed out of necrotic regions. To compare myocardial cell metabolism
      with membrane dysfunction as indicators of necrosis/viability, 43 patients with
      evolving myocardial infarction and coronary arteriography had positron emission
      tomography using fluorodeoxyglucose (FDG) and the potassium analog 82Rb. Percent
      of heart showing FDG defects and 82Rb washout on sequential images indicating
      failure to retain the potassium analogue were visually assessed and quantified by
      automated software. Infarct size based on rubidium kinetics correlated closely
      with size and location on FDG images (visual r = 0.93, automated r = 0.82),
      suggesting that loss of cell membrane integrity for trapping the potassium analog
      82Rb parallels loss of intracellular glucose metabolism, both comparable
      quantitative markers of myocardial necrosis/viability.

PMID- 1988612
TI  - Dosimetric estimates for clinical positron emission tomographic scanning after
      injection of [18F]-6-fluorodopamine.
AB  - Positron emission tomographic (PET) scanning after systemic i.v. injection of
      fluorine-18-6-fluorodopamine ([18F]-6F-DA) is a method for visualizing and
      measuring regional sympathetic nervous system innervation and function. Based on
      results of preclinical studies of rats and dogs and on previous literature about
      the fate of injected tracer-labeled catecholamines, dosimetric estimates for
      clinical studies are presented here. After injection of 1 mCi of [18F]-F-DA, the
      radiation dose would be highest to the wall of the urinary bladder (1.40
      rem/mCi), due to accumulation of radioactive metabolites of [18F]-F-DA in urine.
      Radioactivity also would accumulate in bile. Organs receiving the next highest
      dose would be the kidneys (0.9 rem/mCi) and small intestine (0.2 rem/mCi). The
      parenchymal radiation dose would be lowest in the brain, since there is an
      effective blood-brain barrier for circulating catecholamines. Radiation doses to
      all organs after administration of 1 mCi of [18F]-F-DA to humans would be less
      than 3 rem and, therefore, within current FDA guidelines.

PMID- 1988613
TI  - Sensitivity of technetium-99m-d,1-HMPAO to radiolysis in aqueous solutions.
AB  - The sensitivity of technetium-99m- (99mTc) d,l-HMPAO to radiolytically induced
      dissociation in aqueous solutions was investigated. It was found that cobalt-60
      (60Co) gamma irradiation of solutions containing 99mTc-d,l-HMPAO with only 1600
      cGy reduced the lipophilic chelates' radiochemical purity (RCP) to 50%-60%. The
      radiolytic sensitivity of 99mTc-meso-HMPAO is significantly lower. The results
      indicate that radiolytically produced intermediates limit the in vitro stability
      of 99mTc-d,l-HMPAO.

PMID- 1988614
TI  - Antigen-binding site protection during radiolabeling leads to a higher
      immunoreactive fraction.
AB  - It is generally accepted that the immunointegrity of an antibody (Ab) depends on
      the preservation of its antigen-binding sites. Our goal was to radiolabel an
      antibody at several iodine:antibody molar ratios under conditions protecting its
      combining site and to compare its immunoreactive fraction (IRF) and
      electrophoretic mobility with those of the same antibody radiolabeled without
      protection. The data indicate that an antibody radiolabeled while its antigen
      binding site is occupied by its antigen had the same IRF, regardless of the
      number of iodine atoms per antibody molecule. On the other hand, even at an I:Ab
      ratio of 1:1, the IRF of the same antibody radiolabeled without protection was
      lower than that of a protected one and decreased with increasing I:Ab ratios. In
      addition, the iodination of these Ab changes their electrophoretic mobility;
      however, when the Ab is labeled in the protected state, the degree of change is
      less. The binding of an antibody to its antigen prior to radiolabeling,
      therefore, enhances its immuno-integrity and prevents major conformational
      changes as reflected by electrophoresis.

PMID- 1988615
TI  - The advantage of protecting the antigen-binding site during antibody labeling.

PMID- 1988616
TI  - Indium-111-labeled leukocyte scan in detection of synthetic vascular graft
      infection: the effect of antibiotic treatment.
AB  - To determine the sensitivity and specificity of the indium-111-(111In) labeled
      leukocyte scan for prosthetic vascular graft infection in patients treated with
      antibiotic therapy, a retrospective study was performed. Of 41 consecutive 111In
      labeled leukocyte scans performed to evaluate possible vascular graft infection,
      23 scans were performed in patients treated with antibiotics. The average
      duration of antibiotic therapy was 21 days. Twelve positive and 11 negative scans
      for graft infection were found. By surgical and autopsy correlation of all
      positive cases, and clinical correlation (of all negative cases), there were 10
      true-positive, 11 true-negative, 2 false-positive, and no false-negative scans
      for graft infections, for an overall sensitivity of 100% and specificity of 85%.

PMID- 1988617
TI  - Detection of myocardial viability with positron emission tomography in a patient
      with ischemic cardiomyopathy.

PMID- 1988618
TI  - Bronchobiliary fistula detected by cholescintigraphy.
AB  - We present a case of a bronchobiliary fistula initially detected by hepatobiliary
      scintigraphy. The patient developed bilioptysis 18 mo after undergoing a right
      hepatic lobectomy and resection of the common bile duct for cholangiocarcinoma.
      The procedure was complicated by the development of a subphrenic abscess that
      required percutaneous biliary drainage.

PMID- 1988619
TI  - Microvascular right-to-left pulmonary shunt demonstrated by a radionuclide
      method.
AB  - A 37-yr-old man with angiolymphoid hyperplasia (Kimura's syndrome), who had been
      treated unsuccessfully for suspected asthma, was investigated due to a decrease
      in arterial oxygen saturation (86%). Right heart catheterization and angiography
      of the pulmonary artery failed to demonstrate any right-to-left shunts. However,
      simultaneous scintigraphy over the lungs, kidneys, and head after injection of
      150 MBq technetium-99m-labeled macroaggregated albumin i.v. and inhalation of 150
      MBq krypton-81m demonstrated a right-to-left shunt in the lungs probably caused
      by precapillary pulmonary arteriovenous shunts.

PMID- 1988621
TI  - National Research Council Board recommends restructuring of U.S. HLRW disposal
      program.

PMID- 1988620
TI  - Validation of the circular harmonic transform (CHT) algorithm for quantitative
      SPECT.
AB  - The purpose of this study was to validate the use of the circular harmonic
      transform (CHT) algorithm for quantitative single-photon emission computed
      tomography (SPECT) with isotopes technetium-99m (99mTc) and indium-111 (111In)
      under clinically relevant conditions. Phantom studies were the principal tools
      used. Volumes of fillable organs within a tissue-equivalent anthropomorphic
      phantom were determined over a wide range (145-1960 ml) to within 6% by using a
      thresholding technique. Additionally, phantom studies with nonuniform activity
      distributions were made. These included a background of activity and hot as well
      as cold lesions. The hot lesion was computed to within 12% (111In) and 7.7%
      (99mTc), and contrast in the cold lesion was approximately 70% for both isotopes.
      The CHT algorithm incorporates the energy-distance relation (EDR) which minimizes
      the degrading effects of attenuation, scatter, collimator blur and poor
      statistics.

PMID- 1988622
TI  - Intestinal activity visualized on radionuclide cisternography in patients with
      cerebrospinal fluid leak.
AB  - Several methods are used in conjunction with radionuclide cisternography for
      detecting cerebrospinal fluid (CSF) rhinorrhea or otorrhea, including positioning
      of the patient to induce drainage, placing cotton pledgets in the nostrils and
      ears for scintillation counting, and increasing the CSF pressure within the
      subarachnoid space. Presented here are three surgically proven cases of CSF leak
      where intestinal activity was detected at different intervals following the
      lumbar intrathecal administration of indium-111-DTPA for radionuclide
      cisternography. We recommend the addition of an abdominal image during
      radionuclide cisternography for CSF liquorrhea.

PMID- 1988623
TI  - Validation of simultaneous PET emission and transmission scans.
AB  - A technique for performing simultaneous PET emission and transmission scans is
      validated in a fluoro-deoxyglucose study. A point source masked into a fan beam
      of annihilation photons orbits the patient section under study. Coincident events
      are sorted into two buffers, or rejected, based on the source's position. Both
      static and dynamic frames of independent and simultaneous studies are compared.
      The noise effective count rate is reduced to 62% of the value during normal
      studies. However, the increase in the coefficient of variation in cortical
      regions is less than 6%. The RMS difference between profile contours through many
      brain regions is approximately 40% higher comparing two simultaneous
      emission/transmission scans than when the same analysis is performed on
      independent emission scans. This difference appears to be due to the noise
      patterns arising from the use of different transmission scans.

PMID- 1988624
TI  - L-methionine uptake by human cerebral cortex: maturation from infancy to old age.
AB  - Age-associated changes in amino acid transport from blood to normal frontal
      cortex were studied using positron emission tomography (PET). Seventeen patients,
      1.8-71 yr, were injected intravenously with tracer doses of [11C] L-methionine
      and a baseline PET scan was obtained. To assess competitive inhibition of [11C]L
      methionine uptake, patients received either oral L-phenylalanine or an i.v.
      infusion of amino acids 1 hr before a second PET study. Uptake of [11C]L
      methionine by frontal cortex decreased seven-fold between 1.8 and 71 yr (r = 
      0.71; p less than 0.05). Blood-to-brain transfer of [11C]L-methionine, at 4.5 yr,
      exceeded mean adult values by more than five-fold. Competitive inhibition reduced
      L-methionine uptake in all patients older than 4.6 yr. These developmental
      changes parallel findings in animals. The neutral amino acid transport system may
      modulate human brain amino acid levels to meet changing developmental metabolic
      needs.

PMID- 1988625
TI  - A segmented attenuation correction for PET.
AB  - A segmented attenuation correction technique has been developed for positron
      emission tomography which computes attenuation correction factors automatically
      from transmission images for use in the final image reconstruction. The technique
      segments the transmission image into anatomic regions by thresholding the
      histogram of the attenuation values corresponding to different regions such as
      soft tissue and lungs. Average values of attenuation are derived from these
      regions and new attenuation correction factors are computed by forward projection
      of these regions into sinograms for correction of emission images. The technique
      has been tested with phantom studies and with clinical cardiac studies in
      patients for 30- and 10-min attenuation scan times. This method for attenuation
      correction was linearly correlated (slope = 0.937 and r2 = 0.935) with the
      standard directly measured method, reducing noise in the final image, and
      reducing the attenuation scan time.

PMID- 1988626
TI  - Symbiotic developments in PET and SPECT to quantify and display myocardial
      tomography.

PMID- 1988627
TI  - Radiation safety considerations for post-iodine-131 hyperthyroid therapy.
AB  - The purpose of this study was to develop guidelines based on patient measurements
      as to when iodine-131- (131I) treated hyperthyroid patients may resume close
      personal contact. External exposure rates were measured on 59 patients using an
      ionization survey meter in the upright position. The initial measurement was
      recorded within 20 min post-dose administration at one meter. Exposure rates were
      measured 2-11 days post-dose administration at 1, 0.6, and 0.3 meters from the
      patient's thyroid. In the administered dose range of 3 to less than 12 mCi of
      131I, all 40 patients measured less than or equal to 2.0 mR/hr at one meter on
      Day 0, and 25 patients (25/29) were less than or equal to 2.0 mR/hr at 0.6 meter
      on Days 2-4. Guidelines can be prepared based on the administered dose that are
      rational and in conformity with existing radiologic health standards.

PMID- 1988628
TI  - Therapeutic radionuclides: production and decay property considerations.
AB  - The development of effective therapeutic radiopharmaceuticals requires careful
      consideration in the selection of the radionuclide. The in vivo targeting and
      clearance properties of the carrier molecule must be balanced with the decay
      properties of the attached radionuclide. Radionuclides for therapeutic
      applications fall into three general categories: beta-particle emitters, alpha
      particle emitters, and Auger and Coster-Kronig-electron emitters following
      electron capture. Alpha particles and Auger electrons deposit their energy over
      short distances with a high LET that limits the ability of cells to repair damage
      to DNA. Despite their high levels of cytotoxicity, the relatively short range of
      alpha particles requires binding of the carrier molecule to most cancer cells
      within a tumor in order to be effective. Because of the extremely short range of
      Auger electrons, the radionuclide must be carried directly into the nucleus to
      elicit high radiotoxicity, making it necessary to deliver the radionuclide to
      every cell within a tumor cell population. These characteristics impose rigid
      restrictions on the nature of the carrier molecules for these types of particle
      emitters but successful targeting of these types of radionuclides could result in
      high therapeutic ratios. Most beta-emitting radionuclides are produced in nuclear
      rectors via neutron capture reactions; however, a few are produced in charged
      particle accelerators. For radionuclides produced by direct neutron activation,
      the quantities and specific activities that can be produced are determined in
      large part by the cross-section of the target isotope and the flux of the
      reactor. Many applications (e.g., therapeutic bone agents, radiolabeled
      microspheres, radiocolloids) do not require high-specific activities and can
      therefore utilize the wide range of radionuclides that can be produced in
      sufficient quantity by direct neutron activation. Other applications (e.g., MAb
      labeling) require high-specific activity radionuclides in order to deliver a
      sufficient number of radionuclide atoms to the target site without saturating the
      target or compromising the integrity of the carrier molecule. Most radionuclides,
      produced at NCA levels in reactors, are produced via indirect reactions. High
      specific activity beta emitters can also be obtained from radionuclide generator
      systems where the longer-lived parent radionuclide may be obtained from direct
      neutron activation, as a fission product, or from charged-particle accelerators.
      It is essential that the half-life of a radionuclide used in RNT be compatible
      with the rates of localization in target tissues and clearance of the carrier
      molecule from normal tissues. This consideration is especially important for the
      various MAbs and their fragments that are currently under investigation as
      carrier molecules to RIT.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1988629
TI  - Extrahepatic uptake of technetium-99m-phytate.

PMID- 1988630
TI  - Influence of region of interest selection on the scatter multiplier required for
      quantification in dual-window Compton correction.

PMID- 1988631
TI  - Imaging human brain development with positron emission tomography.

PMID- 1988632
TI  - Long-term follow-up in toxic solitary autonomous thyroid nodules treated with
      radioactive iodine.
AB  - The long-term effects of radioiodine treatment on thyroid function in patients
      with a toxic solitary autonomous thyroid nodule were evaluated. Fifty-two
      patients received a therapeutic dose of 20 mCi of iodine-131 (131I). Duration of
      follow-up was 10 +/- 4 yr. Follow-up data included a biochemical evaluation of
      thyroid function. The failure rate (recurrent hyperthyroidism) was 2%. The
      incidence of hypothyroidism was 6% and was not related to the dose per gram of
      nodular tissue. Oral administration of 20 mCi of radioiodine is a simple and
      highly effective method for the treatment of patients with a toxic autonomous
      thyroid nodule. The risk of development of hypothyroidism is low if extranodular
      uptake of 131I is prevented. This can be achieved by not treating euthyroid
      patients, by no longer using injections of exogenous thyroid stimulating hormone
      in the diagnostic work-up of the patients and by always performing radioiodine
      imaging shortly before treatment.

PMID- 1988633
TI  - The autonomously functioning thyroid nodule.

PMID- 1988634
TI  - Bone scanning in the early assessment of nasal bone graft viability.
AB  - This study examined the role of radionuclide bone scanning in the early
      assessment of free autologous cancellous bone grafts in augmentation rhinoplasty
      and compared the failure rates of grafts taken from the calvaria and ilium.
      Twenty patients had three-phase bone scanning of the facial regions performed
      between 2 and 15 wk after rhinoplasty, and a comparison was made with the results
      of clinical assessment and X-ray findings 3 mo after surgery. Eleven patients had
      grafts taken from the calvaria and nine had iliac grafts. On lateral views, bone
      graft uptake of isotope, which was less than or equal to the adjacent soft
      tissue, was found in 2 out of 20 patients and this finding predicted subsequent
      graft failure as measured by clinical assessment and X-ray evidence of bone
      resorption. Both failures had grafts taken from the calvaria while none from the
      ilium failed. These failure rates, however, were not significantly different.

PMID- 1988635
TI  - Clinical validation of a miniature nuclear probe system for continuous on-line
      monitoring of cardiac function and ST-segment.
AB  - A new, miniature cesium iodide/photodiode nuclear probe (the "Cardioscint") has
      been developed for continuous on-line measurement of left ventricular function
      and the ST-segment. Ejection fraction (EF) measurements in 77 patients were
      compared with gated equilibrium radionuclide ventriculograms. The probe was
      positioned over the left ventricle by first using a blind positioning algorithm
      and then by using the gamma camera. Background was measured both manually and
      automatically. There was good correlation between probe (positioned blind) and
      gamma camera EF with both manual (r = 0.80, n = 65) and automatic (r = 0.78, n =
      66) backgrounds. Use of the gamma camera did not significantly alter the results.
      Correlation between the probe stroke counts and thermodilution-derived stroke
      index during atrial pacing in six subjects was also satisfactory (r = 0.69, n =
      102). Thus, the Cardioscint is able to provide a reliable estimate of EF and can
      track rapid changes in cardiac volumes.

PMID- 1988636
TI  - Continuous radionuclide monitoring of left ventricular function: has the time
      come?

PMID- 1988637
TI  - Quantification of hepatobiliary function as an integral part of imaging with
      technetium-99m-mebrofenin in health and disease.
AB  - A study was undertaken to check the feasibility of measuring the hepatic
      extraction fraction (HEF) and excretion T-1/2 values as an integral part of
      hepatobiliary imaging with technetium-99m-mebrofenin in health and disease. In 18
      controls subjects, the HEF was 100% and the T-1/2 excretion mean +/- s.e. value
      was 15.23 +/- 1.4 min. The mean appearance times of the common bile duct (CBD),
      gallbladder (GB), and small intestine were 15.8 +/- 1.52, 20.2 +/- 2.7, and 23.8
      +/- 3.08 min, respectively. Rising serum bilirubin in patients decreased HEF and
      increased T-1/2 excretion value resulting in delayed appearance of CBD, GB, and
      small intestine. In control subjects and patients with bilirubin less than 5 mg%,
      T-1/2 excretion values at 30, 40, and 50 min were similar to those values
      calculated using the entire 60 min of data, suggesting that the hepatic phase
      study time could be reduced to 30-40 min and still use the normal reference
      values established for 60 min. In patients with bilirubin greater than 5 mg%, the
      data collection duration should be continued for 60 min.

PMID- 1988638
TI  - Sensitivity of measurements of regional brain activation with oxygen-15-water and
      PET to time of stimulation and period of image reconstruction.
AB  - Measurement of oxygen-15- (15O) water uptake with positron emission tomography
      (PET) is a sensitive technique to monitor regional brain activation secondary to
      stimulation paradigms. In order to investigate data acquisition times that show
      maximal changes in regional activation and to assess the optimal time for
      stimulus presentation, we investigated 10 controls with 15O-water and PET during
      baseline and stroboscopic light stimulation. Sequential scans were done varying
      the time of stimulus presentation. The images were reconstructed using three
      different periods of data acquisition: uptake phase (initial 30-35 sec), washout
      phase (40 sec following peak activity in brain), and total activity (3 min). The
      images reconstructed during the uptake phase showed the largest changes in
      occipital cortex from stimulation. Maximal changes in occipital cortex were
      obtained when the visual stimulus was maintained during the uptake phase only.

PMID- 1988639
TI  - Indium-111-chloride and three-phase bone scintigraphy: a comparison for imaging
      experimental osteomyelitis.
AB  - To investigate the utility of indium-111-chloride (111In-Cl) imaging in detecting
      osteomyelitis complicating surgical or fracture sites, the proximal tibia of 11
      dogs were experimentally infected with Staphylococcus aureus after creation of a
      cortical defect. The contralateral limb served as a sham-operated control.
      Animals were serially imaged by radiography, three-phase technetium-99m-methylene
      diphosphonate (99mTc-MDP) scintigraphy, and 111In-Cl scintigraphy. There was a
      significant difference between infected (1.93) and noninfected (1.32) limb's
      tibia/femur count density ratios on 24-hr (p = 0.0001) and 72-hr (p = 0.0001)
      111In-Cl images. A smaller difference was found for 99mTc-MDP bone-phase
      tibia/femur ratios (p = 0.0199). Using receiver operator characteristic analysis
      of tibia/femur ratios, a sensitivity of 61%, specificity of 88%, and positive
      (75%) and negative (79%) predictive values were determined for the 24-hr 111In-Cl
      images. Indium-111-chloride was superior to 99mTc-MDP in differentiating infected
      and noninfected operative sites.

PMID- 1988640
TI  - In vitro and in vivo characterization of 4-[125I]iododexetimide binding to
      muscarinic cholinergic receptors in the rat heart.
AB  - 4-[125I]iododexetimide binding to muscarinic cholinergic receptors (mAChR) was
      evaluated in the rat heart. 4-[125I]iododexetimide displayed high in vitro
      affinity (Kd = 14.0 nM) for rat myocardial mAChR. In vivo, there was high
      accumulation of 4-[125I]iododexetimide in the rat atrium and ventricle which
      could be blocked by approximately 60% by preinjection of atropine. In contrast,
      accumulation of the radiolabeled stereoisomer, 4-[125I]iodolevetimide, was 63%
      lower than 4-[125I]iodolevetimide and was not blocked by atropine. The blood
      clearance of 4-[125I]iododexetimide was rapid, providing heart-to-blood ratios of
      up to 14:1; however, heart-to-lung and heart-to-liver ratios were below unity.
      The data indicate that 4-[125I]iododexetimide binds potently to rat mAChR.
      However, since nonspecific binding is relatively high, it is not clear whether
      iododexetimide labeled with 123I will be useful in SPECT imaging studies of
      myocardial mAChR. Further studies in humans are indicated.

PMID- 1988641
TI  - 20-[18F]fluoromibolerone, a positron-emitting radiotracer for androgen receptors:
      synthesis and tissue distribution studies.
AB  - To develop an androgen receptor-based, positron-emitting imaging agent for
      prostate tumors, we have prepared 20-fluoromibolerone (F-Mib) and evaluated its
      tissue distribution. This compound was synthesized in eight steps from 7 alpha
      methyl-19-nortestosterone, with fluorine introduced in the penultimate step by
      fluoride ion displacement on a spirocyclic sulfate. Fluoromibolerone was obtained
      in 9%-19% radiochemical yield (decay corrected), at 1.5 hr after bombardment,
      with an effective specific activity of 217-283 Ci/mmol. The relative binding
      affinity of F-Mib is 53 (versus R1881 = 100 or mibolerone = 118). In tissue
      distribution studies in diethylstilbestrol-treated male rats, 18F-Mib
      demonstrates high target/tissue uptake efficiency and selectivity: the prostate
      uptake at 0.5 hr and 4 hr is 1.0%-1.3% injected dose/gram tissue (ID/g) and 0.5%
      0.6% ID/g, respectively; the prostate-to-blood and the prostate-to-muscle (non
      target) ratios are both ca. 4 at 0.5 hr, and increase to ca. 12 by 4 hr after
      injection. The observed distribution of 18F-Mib suggests that it may be useful
      for in vivo imaging of prostatic tumors in man by positron emission tomography.

PMID- 1988643
TI  - Hospitalization of a child is a family affair.

PMID- 1988642
TI  - Radioimmunodetection of degranulated human eosinophils in mice: a potential model
      for imaging Hodgkin's disease and other pathologic conditions.
AB  - Various human tumors such as lymphomas and carcinomas sometimes contain extensive
      infiltration by degranulating eosinophils. To determine if degranulated
      eosinophils are suitable targets for immunolocalization, we performed in vivo
      distribution and imaging studies in mice, using EOS (a murine monoclonal antibody
      directed to human eosinophil peroxidase) labeled with indium-111. Adult mice were
      injected intravenously with radiolabeled EOS antibody or with similarly
      radiolabeled normal mouse IgG before receiving an intramuscular injection into
      the right thigh of homogenized human eosinophils adsorbed to latex microspheres.
      There was striking localization in the right thigh of the radiolabeled EOS
      antibody detectable by gamma imaging techniques as soon as 24 hr after injection.
      By contrast, there was little accumulation of radiolabeled normal IgG in the
      right thigh. We conclude that human eosinophil peroxidase is potentially a
      suitable target for radioimmunodetection and therapy of neoplasms and pathologic
      conditions that contain degranulating eosinophils.

PMID- 1988644
TI  - Parenting: categories for anticipatory guidance.
AB  - A descriptive cross-sectional study of 174 parents of well children was conducted
      to elicit parental perceptions of anticipatory guidance needs. An interest in
      anticipatory guidance was expressed by 69% of the parents. Specific topics
      identified by parents were coded into three categories of anticipatory guidance
      for parenting: general parenting, child age-specific, and parental self-care.
      General parenting included the most topics, the majority of which suggested that
      social and behavioral issues are major concerns for parents.

PMID- 1988645
TI  - The relationship between social support and depression in adolescents.
AB  - In a non-clinical, adolescent sample, this correlational study tested the
      hypothesis that there will be an inverse correlation between perceived social
      support and depression. This hypothesis is consistent with the theoretical
      literature. The results suggest that perceived social support is associated with
      depression in adolescents.

PMID- 1988646
TI  - The delivery of mental health services to children.

PMID- 1988647
TI  - Music listening preferences and preadmission dysfunctional psychosocial behaviors
      of adolescents hospitalized on an in-patient psychiatric unit.
AB  - This study investigated the relationship between music listening preferences and
      preadmission, dysfunctional psychosocial behaviors (PDPB) of 60 adolescents who
      were hospitalized on an in-patient psychiatric unit. Findings were that
      hospitalized adolescents who primarily listened to music with negative
      lyrics/themes had a history of more PDPB than hospitalized adolescents who
      primarily listened to music that did not contain negative lyrics/themes; and
      hospitalized adolescents who primarily listened to heavy metal music had a
      history of more PDPB than hospitalized adolescents who primarily listened to
      other types of music.

PMID- 1988648
TI  - Developing problem-solving skills of adolescents. A model intervention program.

PMID- 1988650
TI  - Protein kinase C translocation in rat stomach fundus: effects of serotonin,
      carbamylcholine and phorbol dibutyrate.
AB  - In an effort to characterize serotonergic receptor activation in rat stomach
      fundus, the potential role of protein kinases, more specifically protein kinase C
      (PKC), in serotonin-induced contraction of rat stomach fundus was examined.
      Staurosporine, a potent, but nonselective, inhibitor of protein kinases,
      attenuated basal, membrane-bound PKC activity in rat stomach fundus (IC50 = 10
      nM). Although staurosporine (3-100 nM) produced a concentration-dependent
      inhibition of contractions elicited by serotonin (which does not increase
      phosphatidylinositol hydrolysis in the fundus), carbamylcholine (an agent
      stimulating phosphatidylinositol hydrolysis), and phorbol 12,13-dibutyrate (PDBu;
      a phosphatidylinositol-independent activator of PKC translocation), it was a more
      potent inhibitor of contractions produced by serotonin and PDBu than by
      carbamylcholine. Potassium chloride-induced contractions were attenuated
      minimally by staurosporine. These results raised the possibility that serotonin
      might exert an effect on protein kinase activity by a phosphatidylinositol
      independent mechanism. Focusing on PKC, serotonin's ability to translocate PKC
      from cytosol to membrane in rat fundus was examined. Concentrations of serotonin
      (0.1-10 microM) which maximally contracted rat fundus did not translocate PKC.
      However, PDBu (10 nM-1 microM) and carbamylcholine (0.1-10 microM) significantly
      increased membrane-bound PKC activity. These results: 1) demonstrate that
      translocation of PKC occurred in rat stomach fundus in response to some, but not
      all, contractile agonists; 2) are consistent with the possibility that
      contraction of rat stomach fundus by carbamylcholine and PDBu may be related to
      increased membrane-bound PKC activity; and 3) indicate that serotonin-induced
      contraction, although potently blocked by staurosporine, did not result from PKC
      translocation in the rat stomach fundus.

PMID- 1988649
TI  - Adolescent anger: a developmental study.
AB  - This research examined adolescent anger in a cohort of adolescents measured
      twice, once during the freshman year and again in the senior year of high school.
      Anger was measured by the Anger Index, a questionnaire developed by Siegel
      (1984). The purpose of the research was to determine if adolescent anger changed
      over time and if there were gender differences. Results of the study indicated
      that anger scores appeared to be stable over time for both boys and girls. There
      were gender and time differences on individual responses for several items,
      indicating that certain dimensions of anger may differ over time and by gender.
      It also appeared possible that the interpretation of certain questions on the
      anger index was different for the adolescents at the two time intervals.

PMID- 1988651
TI  - Renal and femoral vascular responses to endothelin-1 in dogs: role of
      prostaglandins.
AB  - Vascular responses to endothelin were examined with special reference to
      prostaglandins (PGs). Intrarenal infusion of endothelin (ET)-1 (1-5 ng/kg/min) to
      dogs caused a transient increase followed by a sustained decrease in renal blood
      flow, with no change in blood pressure or heart rate. Renal secretion rates of
      PGE2 and I2 (determined as 6-keto PGF1 alpha) were increased with ET, dose
      dependently, and the intrarenal infusion of ET (5 ng/kg/min) elevated the
      systemic arterial concentration of 6-keto PGF1 alpha from 26 +/- 5 to 83 +/- 14
      pg/ml. Because this increase in PG secretion was not affected by the platelet
      activating factor antagonist, CV 6209, it is unlikely that ET-induced renal PG
      production was platelet activating factor-mediated. Pretreatment with aspirin
      abolished completely the increased PG secretion elicited by ET and potentiated
      the ET-induced reduction renal blood flow. Intrafemoral infusion of ET (5
      ng/kg/min) also induced an initial increase followed by a gradual decrease in
      femoral blood flow, without any increase in PG secretion from the hindlimb.
      Aspirin had no effects on the femoral hemodynamic action of ET. In addition,
      initial transient increases in either renal or femoral blood flow by endothelin
      were not affected by aspirin. Thus, the ET-induced production of renal PGs
      counteracts the renal vasoconstrictor action of ET, an event in marked contrast
      to the lack of any apparent involvement of PGs in the femoral hemodynamic action
      of ET. The ET-induced transient vasodilation shows no apparent relation to the
      cyclooxygenase products.

PMID- 1988652
TI  - Regional and systemic hemodynamic effects of parathyroid hormone-related protein:
      preservation of cardiac function and coronary and renal flow with reduced blood
      pressure.
AB  - It has been demonstrated previously that parathyroid hormone-related protein
      (PTHrp) has potent vasodilatory and cardiac stimulatory properties. However, the
      systemic and regional hemodynamic effects of PTHrp are unknown. In order to
      characterize these effects, we utilized the radioactive microsphere technique to
      examine the systemic and regional hemodynamics before and 2 min after the i.v.
      bolus administration of 0.03, 0.3 and 3.0 micrograms/ml/100 g b.wt. of PTHrp in
      conscious, unrestrained, normal rats. These effects were compared to those of
      synthetic rat parathyroid hormone (PTH), an agent known to affect cardiovascular
      function. PTHrp and PTH similarly and significantly decreased mean systemic blood
      pressure and total peripheral resistance but increased heart rate and cardiac
      output, all in a dose-dependent manner. Both peptides increased blood flow and
      decreased vessel resistance in regional vascular beds such as skin and heart.
      Renal resistance was reduced by PTH and PTHrp, but renal blood flow was not
      altered. Conversely, both peptides significantly decreased blood flow and
      increased vascular resistance to the splanchnic organs. Thus, PTHrp as well as
      PTH, preserved and enhanced cardiac function in the face of reduced systemic
      blood pressure while maintaining renal flow. These features are highly desirable
      in the treatment of some severe cardiovascular abnormalities. These results are
      consistent with the hypothesis that PTHrp may play an important hormonal,
      autocrine or paracrine role in systemic and regional blood flow regulation.

PMID- 1988653
TI  - Behavioral and neurochemical interactions between cocaine and buprenorphine:
      implications for the pharmacotherapy of cocaine abuse.
AB  - Intravenous self-administration studies in nonhuman primates suggest that the
      opioid receptor agonist-antagonist buprenorphine may be useful in the
      pharmacotherapy of cocaine abuse. In the present studies, behavioral and
      neurochemical interactions between cocaine and buprenorphine were examined using
      a conditioned place preference (CPP) procedure and in vivo microdialysis. Cocaine
      induced CPP was linearly related to the dose administered (0-5.0 mg/kg).
      Buprenorphine (0-0.9 mg/kg) also elicited CPP in a dose-related manner; an
      inverted U-shaped function was obtained. Subthreshold doses of cocaine (1.5
      mg/kg) and buprenorphine (0.01 mg/kg), themselves incapable of eliciting CPP,
      produced a significant CPP when given together. Moderate doses of cocaine (5.0
      mg/kg) and buprenorphine (0.075 mg/kg), which were individually capable of
      eliciting CPP, produced a significantly larger CPP when given in combination. In
      the in vivo microdialysis studies, a low dose of buprenorphine (0.01 mg/kg)
      produced a progressive increase in extracellular dopamine in the nucleus
      accumbens, reaching approximately 200% of basal levels after 5 hr. Cocaine (5.0
      mg/kg) rapidly increased extracellular dopamine concentrations (180% of basal
      values within 20 min), which returned to baseline in 2 to 3 hr. This effect of
      cocaine was significantly potentiated by coadministering buprenorphine (0.01
      mg/kg); under this condition the peak increase in extracellular dopamine reached
      260% of baseline values. These neurochemical findings are consistent with the CPP
      results and indicate that buprenorphine can interact with cocaine in a
      synergistic manner. In contrast to previous speculations, these results suggest
      that buprenorphine may enhance rather than attenuate the rewarding properties of
      cocaine.

PMID- 1988654
TI  - Concentration-dependence of acetylcholine-induced changes in calcium and tension
      in swine trachealis.
AB  - Acetylcholine (ACh)-induced increases in intracellular calcium concentration
      ([Ca++]i) and tension were measured simultaneously in swine tracheal smooth
      muscle strips loaded with the calcium-sensitive fluorescent dye Fura-2. ACh at
      concentrations greater than or equal to 3 x 10(-8) M induced concentration
      dependent increases in tension which reached a maximum at 10(-4) M. Increases in
      [Ca++]i occurred at all [ACh] tested (10(-8) to 10(-4) M). After addition of ACh
      at concentrations greater than 3 x 10(-7) M, [Ca++]i increased rapidly to a
      concentration dependent-peak then declined to a concentration-independent steady
      state approximately 250 nM above the resting [Ca++]i of 257 +/- 12 nM. There was
      a steep relationship (slope factor greater than 3) between the peak tension and
      the peak [Ca++]i reached at each [ACh]. The rate of decline of [Ca++]i to the
      steady state at [ACh] greater than 73 x 10(-7) M was well correlated with the
      peak [Ca++]i reached. We conclude that the peak increase in calcium induced by
      ACh sets the level of tension to be attained and the rate of decline of the
      transient increase in [Ca++]i. The steady-state [Ca++]i is sufficient for
      maintenance of tension.

PMID- 1988655
TI  - Characterization of serotonin receptors in isolated rat intramyocardial coronary
      artery.
AB  - The purpose of the present study was to characterize the receptor subtypes that
      mediate serotonin (5-HT)-induced contraction in isolated rat intramyocardial
      coronary artery. In coronary artery with and without endothelium, only 5-HT and
      alpha-methylserotonin maleate (5-HT2 agonist) elicited equipotent concentration
      dependent contractions. The EC50 values for 5-HT and alpha-methylserotonin
      maleate in endothelium-intact arteries were 4.7 x 10(-7) and 4.5 x 10(-7) M,
      respectively, whereas in endothelium-denuded arteries they were 2.8 x 10(-7) and
      1.9 x 10(-7) M, respectively. The other subtype agonists, such as (+/-)-8-hydroxy
      dipropylaminotetralin hydrobromide (5-HT1A agonist), 1-(3-chlorophenyl)piperazine
      dihydrochloride and 7-trifluoromethyl-4-(4-methyl-1-piperazinyl)-pyrrolo(1,2
      a)quinoxaline (5-HT1B) and 2-methyl-serotonin maleate (5-HT3), only elicited a
      small percentage of the maximum contraction to 5-HT. In prostaglandin F2 alpha
      precontracted coronary arteries with intact endothelium or denuded of
      endothelium, the addition of 5-HT resulted in a further increase in tension. No
      relaxation was observed with 5-HT up to 1 x 10(-5) M. The contraction induced by
      5-HT in artery both with and without endothelium was inhibited by ketanserin (5
      HT2 antagonist) but not by l-propranolol (5-HT1 antagonist) nor by 3-tropanyl
      indole-3,5-dichlorobenzoate (5-HT3 antagonist). Ketanserin, the selective 5-HT2
      antagonist, effectively antagonized 5-HT-induced contraction by shifting the 5-HT
      response curve to the right without inhibiting the maximal response in both
      endothelium-intact and -denuded arteries.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1988656
TI  - Tissue distribution, excretion and hepatic biotransformation of microcystin-LR in
      mice.
AB  - The distribution, excretion and hepatic metabolism of [3H]microcystin-LR
      (sublethal i.v.) were measured in mice. Plasma elimination was biexponential with
      alpha- and beta-phase half-lives of 0.8 and 6.9 min, respectively. At 60 min,
      liver contained 67 +/- 4% of dose. Through the 6-day study the amount of hepatic
      radioactivity did not change whereas 23.7 +/- 1.7% of the dose was excreted; 9.2
      +/- 1.0% in urine and 14.5 +/- 1.1% in feces. Approximately 60% of the urine and
      fecal radiolabel 6 and 12 hr postinjection was the parent toxin. Hepatic cytosol,
      which contained 70 +/- 2% of the hepatic radiolabel (1 hr through 6 days), was
      prepared for high-performance liquid chromatography analysis by heat
      denaturation, pronase digestion and C18 Sep Pak extraction. At 1 hr, 35 +/- 2% of
      the radiolabel was insoluble or C18 Sep Pak-bound; 43 +/- 3% was associated with
      a peak of retention time (rt) 6.6 min, and 16 +/- 3% with the parent toxin (rt
      9.4 min). After 6 days, 8 +/- 1% was C18 Sep Pak-bound or insoluble; 5 +/- 0%
      occurred at rt 6.6 min, 17 +/- 1% with parent and 60 +/- 2% was associated with
      rt 8.1 min. Two other peaks, rt 4.9 and 5.6 min, appeared transiently. Analysis
      of hepatic cytosol by desalting chromatography under nondenaturing and denaturing
      conditions revealed that all of the radiolabel was associated with cytosolic
      components, and 83 +/- 5% was bound covalently through 1 day. By day 6 the amount
      of covalently bound isotope decreased to 42 +/- 11%. This is the first study to
      describe the long-term hepatic retention of microcystin toxin and documents
      putative detoxication products.

PMID- 1988657
TI  - Noncontractile acetylcholine receptor-operated Ca++ mobilization: suppression of
      activation by open channel blockers and acceleration of desensitization by closed
      channel blockers in mouse diaphragm muscle.
AB  - The effects of various blockers of the nicotinic acetylcholine receptor-activated
      ionic channel on noncontractile slow Ca++ mobilization were investigated at the
      neuromuscular synapse of aequorin-injected diaphragm muscles of mice.
      Intracellular Ca++ mobilization (Ca++ transients) was evoked in the presence of
      neostigmine (0.3 microM) by nerve stimulation. Bupivacaine, an open channel
      blocker, decreased the peak amplitude, whereas chlorpromazine, a closed channel
      blocker, shortened the duration. Phencyclidine, an open and closed channel
      blocker, decreased both peak amplitude and duration. beta-Eudesmol, a compound of
      Atractylodes lancea, clearly and specifically shortened the duration but had
      little effect on peak amplitude. All the above channel blockers, when given in
      the same concentration ranges, also blocked the total amount of contractile Ca++
      transients. The effects of bupivacaine, chlorpromazine and phencyclidine on
      noncontractile Ca++ transients were not affected by 5 mM [Ca++]o, whereas the
      effect of beta-eudesmol was enhanced. Geographutoxin II (0.3 microM), a skeletal
      muscle Na+ channel blocker, selectively and partly reversibly blocked contractile
      Ca++ transients without affecting noncontractile ones. These results suggest
      that: 1) the activation of noncontractile Ca++ mobilization is suppressed by open
      channel blockers, whereas its desensitization is accelerated by closed channel
      blockers and 2) activation of the muscle Na+ channel and subsequent release of
      Ca++ from sarcoplasmic reticulum is not involved in the mechanism of
      noncontractile Ca++ mobilization. It may reflect the steps of the desensitization
      process.

PMID- 1988658
TI  - A comparison of the hemodynamic effects of endothelin-1 and sarafotoxin S6b in
      conscious rats.
AB  - The hemodynamic effects of sarafotoxin S6b (SRT) and endothelin-1 (ET-1) were
      studied in conscious, freely moving rats. Intravenous bolus administration of ET
      1 produced an initial transient depressor response and skeletal muscle
      (hindquarters) vasodilation. This depressor activity was not observed after i.v.
      SRT except at a high dose. The initial fall in blood pressure was followed by a
      sustained pressor response and an increase in total peripheral resistance which
      were mediated, at least partially, by visceral (mesenteric) and skeletal muscle
      (hindquarters) vasoconstriction. The durations of the pressor responses and times
      required to achieve the peak pressor effects (peak time) were greater for ET-1 as
      compared to SRT. The results of qualitatively similar sustained hemodynamic
      effects and the strong correlation between the amplitude of the responses to ET-1
      and SRT in individual rats suggest that the sustained pressor responses to these
      peptides are mediated by the same receptors, although the potency was
      significantly greater for ET-1 than for SRT. Furthermore, the initial depressor
      and sustained pressor responses appear to be mediated by distinct receptor
      subtypes inasmuch as the same dose of ET-1 was required for both vasodilator and
      vasoconstrictor activity but a higher dose of SRT was required to elicit its
      vasodilator as compared to constrictor effects. Thus, SRT may have relatively
      lower affinity for receptors mediating its initial hemodynamic responses whereas
      ET-1 binds with equal affinity to both receptors. These potent and vascular
      specific hemodynamic actions suggest a role of endothelin in regulating
      cardiovascular function.

PMID- 1988659
TI  - Low dose verapamil and nitroprusside distinguish tonic from cholinergic-induced
      contractions in in vivo feline lower esophageal sphincter.
AB  - Although in vitro studies suggest that cholinergic induced contractions and
      spontaneous tone are mediated by two different cellular pathways, this has not
      been shown in vivo. The purpose of this study was to distinguish these types of
      contractions in the feline lower esophageal sphincter (LES) through use of i.v.
      selective pharmacologic antagonists. Continuous infusion of the calcium channel
      antagonist verapamil (16-128 micrograms/kg/min) caused a dose-dependent
      inhibition of bethanechol induced and tonic pressure change. At 32.0
      micrograms/kg/min, verapamil produced significantly greater inhibition of
      bethanechol induced contractions when compared with inhibition of basal LES tone
      (57.4 versus 4.8%, P less than .02, n = 5). Verapamil also caused a parallel
      decrease in LES spike activity associated with bethanechol induced contractions.
      In contrast, lower doses of nitroprusside (0.5 micrograms/kg/min) inhibited LES
      tone by over 50% (50.6 +/- 21.8%) yet had no significant effect (16.8 +/- 23.4%)
      on bethanechol induced contractions. Also, inhibition of basal LES tone
      correlated poorly with its effect on associated spike activity. It is concluded
      that in the in vivo feline LES, spike dependent cholinergic contractions can be
      distinguished from LES tone by the use of low dose verapamil and nitroprusside,
      respectively. This selective inhibition suggests that two cellular mechanisms
      mediate LES contractions and that these pathways can be distinguished
      pharmacologically in vivo.

PMID- 1988660
TI  - Enhancing effect by nicotinic acetylcholine receptor channel blockers, including
      beta-eudesmol, on succinylcholine-induced inhibition of twitch tension and
      intracellular Ca++ in mouse diaphragm muscle.
AB  - To elucidate the mechanism of neuromuscular block by succinylcholine, nerve
      evoked changes in intracellular Ca(++)-aequorin luminescence and twitch tension
      were measured simultaneously in the presence of several different types of
      blockers for the nicotinic acetylcholine receptor channel. Mouse diaphragm
      muscles were pretreated for 30 to 60 min with 3 to 40 microM bupivacaine,
      chlorpromazine, phencyclidine and beta-eudesmol. The effects of these
      noncompetitive blockers on the succinylcholine-induced response were also
      compared with those for pancuronium. These channel blockers potentiated (2- to 10
      fold) both the blocking effects on intracellular Ca++ and twitch tension of
      succinylcholine (13-100 microM), but not the pancuronium (0.3-1.1 microM)-induced
      block. These channel blockers also suppressed succinylcholine (1.3-5 microM)
      induced enhancement of evoked Ca++ transients. On the other hand, the channel
      blockers inhibited the succinylcholine (2.5-100 microM)-induced increase in basal
      Ca++ transients. These results suggest that neuromuscular block induced by
      succinylcholine is mainly due to desensitization of the nicotinic acetylcholine
      receptor.

PMID- 1988661
TI  - In vitro pharmacological profile of a novel structural class of oxytocin
      antagonists.
AB  - A number of structurally novel cyclic hexapeptides have been characterized as
      potent and selective oxytocin (OT) antagonists in vitro. As a representative of
      this class of compounds, L-366,948 [[cyclo(L-prolyl-D-2-naphthylalanyl-L
      isoleucyl-D-pipecolyl- L-pipecolyl-D- histidyl)]] exhibited a high binding
      affinity (Ki, low nanomolar) for OT receptors in rat (uterus and mammary) and
      primate (pregnant rhesus and human myometrium) tissue with a several hundred-fold
      binding selectivity vs. rat arginine vasopressin (AVP)-V1 (liver) and AVP-V2
      (kidney medulla) receptors. In functional assays, L-366,948 was a pure OT
      antagonist, blocking both OT-stimulated contraction of the isolated rat uterus
      (pA2, 8.5) and phosphatidylinositol turnover in uterine slices (IC50, 40 vs. 3 nM
      OT), with no evidence of partial agonist activity. L-366,948 was comparatively
      weak as an antagonist of AVP-induced contraction of the isolated rat tail artery
      (AVP-V1 receptor) and AVP-stimulated adenylate cyclase (AVP-V2 receptor) activity
      in rat kidney medulla and did not influence prostaglandin F2 alpha- or bradykinin
      induced contractions of the isolated rat uterus. L-366,948 and related compounds
      described in this report represent new experimental tools for the study of the
      pharmacology and physiology of OT.

PMID- 1988662
TI  - UK-68,798: a novel, potent and highly selective class III antiarrhythmic agent
      which blocks potassium channels in cardiac cells.
AB  - UK-68,798 increased the duration and effective refractory period of cardiac
      action potentials recorded in vitro from canine ventricular muscle and Purkinje
      fibers in a concentration dependent manner from 5 nM to 1 microM. The resting
      membrane potential, amplitude and maximum upstroke velocity of action potentials
      were unaffected by UK-68,798, indicating the selective class III antiarrhythmic
      properties of this agent. UK-68,798 (5 nM-1 microM) increased the effective
      refractory period of isolated guinea pig papillary muscles at stimulation
      frequencies of 1 Hz and 5 Hz without influencing the conduction velocity, further
      confirming that UK-68,798 is devoid of class I antiarrhythmic activity including
      block of the sodium channel. Studies using single voltage clamped guinea pig
      ventricular myocytes indicated that UK-68,798 at concentrations of 50 nM and 2
      microM blocks a time-dependent K+ current, with no appreciable effects on the
      time-independent K+ current or the inward calcium current. UK-68,798 is therefore
      a highly selective K+ channel blocking agent with class III antiarrhythmic
      properties, a profile that holds considerable promise for the therapy of life
      threatening cardiac arrhythmias.

PMID- 1988663
TI  - Antiarrhythmic efficacy of a new class III agent, UK-68,798, during chronic
      myocardial infarction: evaluation using three-dimensional mapping.
AB  - UK-68,798 is a potent class III antiarrhythmic agent that selectively lengthens
      the effective refractory period (ERP) in isolated tissue without affecting
      conduction velocity. The present study was performed to evaluate the
      antiarrhythmic efficacy of UK-68,798 (30 micrograms/kg i.v.) in dogs with a
      previous myocardial infarction. UK-68,798 did not alter the PQ interval or QRS
      duration of the surface electrocardiogram but did increase the Q-Tc interval
      significantly. The ventricular ERP was increased significantly (P less than .01)
      at a basic cycle length of stimulation of either 300 ms (ERP increased 24 +/- 10
      ms) or 250 ms (ERP increased 20 +/- 12 msec), indicating that the response was
      preserved at more rapid rates. UK-68,798 prevented the induction of sustained
      ventricular tachycardia in six of seven animals (86%, P = .03). However, UK
      68,798 failed to prevent the induction of ventricular fibrillation (VF) in dogs
      where VF was the only arrhythmia induced. To evaluate the mechanisms responsible
      for the prevention of ventricular tachycardia and lack of efficacy against
      inducible VF, detailed three-dimensional activation mapping of the heart in vivo
      was used. Induction of ventricular tachycardia was prevented by UK-68,798 due to
      a lengthening of the ERP in the epicardial region surrounding the infarct with no
      effect on conduction velocity even in periinfarct regions bordering the infarct.
      In contrast, the induction of VF was dependent on a rapid nonreentrant or focal
      mechanism that was not altered by the lengthening of ERP with UK-68,798. Thus, UK
      68,798 is a selective class III antiarrhythmic agent that is likely to be
      efficacious in preventing arrhythmias due to a reentrant mechanism in patients
      with a previous myocardial infarction.

PMID- 1988664
TI  - Vasopressin antidiuretic agonist and antagonist activity in dogs: structural and
      stereochemical relationship between bridge and carboxyl terminus.
AB  - A series of vasopressin analogs with various amino acid tail modifications were
      tested for antidiuretic agonist and antagonist (water diuretic) activity in the
      water-loaded indomethacin-treated and hydropenic dogs, respectively. Changing the
      carboxy terminus from Cys6-Pro7-Arg8-NH2 in SK&F 101926 to Cys6-Arg7-NH2 or to D
      Cys6-Pro7-Arg8-NH2 or to D- or L-Cys6-Arg7-D-Arg8-NH2 reduced antidiuretic
      agonist and increased water diuretic activity. Replacement of the sulfur atoms in
      the cysteine residues with methylene groups further reduced the antidiuretic
      agonist activity of all carboxy terminus-modified compounds which possessed full
      agonist activity. It also increased the water diuretic activity of those
      disulfide analogs with both weak agonist and antagonist activity. These results
      indicate that alterations in the geometry of the hexapeptide ring and in the
      stereochemical relationship between the ring and the carboxy terminus of the
      molecule substantially modify the in vivo agonist and antagonist activity of
      vasopressin analogs.

PMID- 1988665
TI  - Serotonergic modulation of the release of endogenous norepinephrine from rat
      hypothalamic slices.
AB  - Ca+(+)-dependent release of endogenous norepinephrine (NE) and dopamine from
      superfused rat hypothalamic slices was stimulated by 40 mM K+. 20 mM K+ released
      only NE. Two consecutive exposures to 20 mM K+ (S1 and S2, respectively) produced
      NE release of similar magnitude (S2/S1 = 1.03 +/- 0.08). Serotonin (5-HT), 3 to
      10 microM, in the presence of methylsergide or ritanserin (antagonists at 5-HT1
      like and 5-HT2 receptors), caused a concentration-dependent decrease of K(+)
      evoked NE release. 5-HT alone did not alter K(+)-evoked NE release. 2-Methyl
      serotonin, 2-methyl-5-hydroxytryptamine, 3 to 10 microM (a selective 5-HT3
      agonist), mimicked the 5-HT response in the presence and in the absence of
      ritanserin. A highly selective 5-HT3 antagonist, (3 alpha-tropanyl)1H-indole-3
      carboxylic acid ester (ICS 205-930), 1 nM, inhibited the effect of both agonists.
      The isomers of another highly selective 5-HT3 antagonist, zacopride, inhibited
      the effect of 2-methyl-serotonin, 2-methyl-5-hydroxytryptamine, at a
      concentration range, 0.03 to 20 nM, characteristic of their interaction with 5
      HT3 receptors. alpha-Methyl-serotonin, alpha-methyl-5-hydroxytryptamine, a
      selective 5-HT1-like/5-HT2 agonist, failed to affect the K(+)-evoked NE release,
      but antagonized the effect of 2-methyl-serotonin, 2-methyl-5-hydroxytryptamine.
      These observations provide direct evidence that, in rat hypothalamus, 5-HT
      modulates release of endogenous NE through activation of 5-HT3 and, possibly, 5
      HT1C receptors.

PMID- 1988666
TI  - BMY 30047: a novel topically active retinoid with low local and systemic
      toxicity.
AB  - In the treatment of various dermatological disorders, topically applied retinoids
      have potential therapeutic use with the advantage of improved localized activity
      and lower toxicity over systemically administered retinoids. However, most
      retinoids cause a significant degree of local irritation. In the present study,
      the ability to produce local activity with low local irritation potential was
      evaluated with a novel retinoic acid derivative. BMY 30047 (11-cis, 13-cis-12
      hydroxymethylretinoic acid delta-lactone) is one of a series of retinoic acid
      derivatives in which the carboxyl function of the polar end was modified with the
      aim of achieving reduced local irritation and systemic toxicity while retaining
      the local therapeutic effect. BMY 30047 was evaluated and compared with all-trans
      retinoic acid for topical retinoid activity in several preclinical assay systems,
      including the utricle reduction assay in rhino mice, 12-o-tetradecanoylphorbol 13
      acetate ester-stimulated ornithine decarboxylase induction in hairless mice and
      the UV light-induced photodamaged skin model in hairless mice. BMY 30047 was
      assessed for retinoid-type side effects by evaluating the skin irritation
      potential in rabbits after repeated topical application, and hypervitaminosis A
      inducing potential in mice after i.p. injection. BMY 30047 demonstrated
      significant topical retinoid activity in several in vivo models with less skin
      irritation potential relative to the most used clinical concentrations of all
      trans retinoic acid. BMY 30047 also showed very little systemic activity and did
      not produce any evidence of hypervitaminosis A syndrome at systemic doses 20
      times greater than the no-effect dose of all-trans retinoic acid.

PMID- 1988667
TI  - Protective behavior of captopril on Hg(++)-induced toxicity on kidney
      mitochondria. In vivo and in vitro experiments.
AB  - Mercurials are known to induce morphological and functional modifications in
      kidney mitochondria. In this work we studied in vitro and in vivo the protective
      effect of captopril on the deleterious effect of Hg(++)-induced nonspecific
      membrane permeability changes to Ca++ and membrane de-energization. In vivo the
      administration of captopril prevented the toxic effects of mercury poisoning on
      membrane permeability, oxidative phosphorylation and Ca++ homeostasis. Moreover,
      captopril preserves kidney tissue morphology from Hg(++)-induced damage. The
      protective effect of captopril is most likely related to the existence of a
      sulfhydryl group in the drug.

PMID- 1988668
TI  - Metabolism and cytotoxicity of naphthalene oxide in the isolated perfused mouse
      lung.
AB  - Naphthalene produces selective injury to Clara cells in the mouse in vivo and in
      the isolated perfused lung. To investigate the role of circulating reactive
      metabolites in lung injury, the stability, metabolism and cytotoxicity of
      naphthalene oxide, a reactive intermediate, were examined in the perfused mouse
      lung. The T1/2 of naphthalene oxide is 4 min in Waymouth's medium. Addition of 5%
      bovine serum albumin to the medium increased the half-life of the epoxide to 11
      min. Perfusion of the lung with 0.2 or 2 mumol of naphthalene oxide decreased
      pulmonary reduced glutathione levels to 62 and 42% of control, respectively. 1,4
      Naphthoquinone and naphthol-glucuronide represented 36 and 25% of the total polar
      metabolites isolated after infusion of naphthalene oxide, whereas dihydrodiol and
      thioether conjugates were minor metabolites. In comparison, thioethers and
      dihydrodiol were the primary metabolites isolated from lungs perfused with
      [14C]naphthalene. Histologic examination of the lungs fixed 4 hr after infusion
      of naphthalene oxide (0.25-1.0 mumol/60 min) revealed selective vacuolation and
      necrosis of Clara cells, significant decreases in the mass of bronchiolar Clara
      cells and increases in the mass of vacuolated cells. Injury to lungs perfused
      with naphthalene or secondary metabolites such as naphthoquinones, 1-naphthol and
      1,2-dihydro-1,2-dihydroxynaphthalene was less dramatic. In contrast to other
      studies implicating quinones as mediators of aromatic hydrocarbon toxicity, the
      current work suggests that epoxides play a significant role in naphthalene
      induced lung injury. This investigation also demonstrates that circulating
      epoxides are capable of eliciting selective Clara cell injury.

PMID- 1988669
TI  - Caffeine potentiates the renin response to diazoxide in man. Evidence for a
      regulatory role of endogenous adenosine.
AB  - In the rat and dog, exogenous adenosine inhibits renin release and adenosine
      receptor blockade augments stimulated renin release, suggesting that endogenous
      adenosine contributes to the regulation of renin release. The present study
      examines the role of endogenous adenosine in the regulation of renin in humans.
      The ability of the adenosine receptor blocker, caffeine, to augment renin release
      in response to the vasodilator, diazoxide, has been investigated in eight normal
      subjects in a double-blind, placebo-controlled, cross-over study. During each arm
      of the study, subjects on a 150 mEq of sodium, xanthine-free diet received
      caffeine (250 mg 3 times daily) or placebo for 3 days before and on the study
      day, when they were given an i.v. loading dose of diazoxide (4 mg/kg) followed by
      a 3-hr continuous infusion (0.67 mg/kg/hour). PRA, caffeine and diazoxide levels
      were measured before, during and after the diazoxide infusion. PRA measurements
      were repeated with subjects standing, 6 hr after starting diazoxide.
      Administration of diazoxide resulted in a modest tachycardia and a small, but
      significant, decrease in BP. Supine PRA was elevated during and after the
      diazoxide infusion and rose further with standing. Although there was no
      difference in plasma diazoxide levels, maximal pulse or BP response to diazoxide
      between the two arms of the study, the renin response was significantly greater
      in the presence of caffeine. These data confirm that caffeine augments the PRA
      response to diazoxide and suggest that endogenous adenosine inhibits stimulated
      renin response in humans.

PMID- 1988670
TI  - Insight into interstitial drug disposition: lymph concentrations of lidocaine,
      procainamide and meperidine in the hindquarters of unanesthetized and
      anesthetized sheep.
AB  - Drug concentrations in the lymph of the hindquarters of sheep were used to gain
      insight into drug disposition within the interstitial space. Lidocaine,
      procainamide and meperidine were each infused into the right atrium of adult
      merino ewes for 220 min. The time courses of drug concentrations in arterial and
      inferior vena caval (IVC, draining the hindquarters) blood and hindquarter lymph
      were determined. It was found that in unanesthetized sheep the mean (+/- S.D., n
      = 3) lidocaine, procainamide and meperidine concentrations in the hindquarter
      lymph, were 74 +/- 11, 107 +/- 25 and 94 +/- 17%, respectively, of the arterial
      and 92 +/- 15, 113 +/- 27 and 134 +/- 28%, respectively, of the IVC blood drug
      concentrations. Drug binding in lymph, determined by equilibrium dialysis, was
      not significantly higher than that in blood, except for lidocaine at an initial
      buffer concentration of 5 micrograms/ml. When the studies were repeated with
      different animals under halothane anesthesia, the lymph/arterial and lymph/IVC
      blood drug concentration ratios of the three drugs decreased to 66 +/- 9, 73 +/-
      13 and 71 +/- 13% and 77 +/- 8, 88 +/- 19 and 85 +/- 10%, respectively. These
      values were all significantly lower than those in unanesthetized animals. The
      results suggest that drug protein binding in interstitial fluid and the status of
      the microcirculation are important determinants of drug distribution in the
      interstitial and intracellular spaces. The data also confirm the assumption made
      in pharmacokinetic studies based upon mass balance principles that the rate of
      drug removal from organs by lymph is negligible.

PMID- 1988671
TI  - Characterization of LY233569 on 5-lipoxygenase and reperfusion injury of ischemic
      myocardium.
AB  - LY233569 produced concentration-dependent inhibition of isolated guinea pig 5
      lipoxygenase (5-LPO) and 5-LPO activity of human polymorphonuclear leukocytes in
      vitro; IC50 values were 0.4 and 0.1 microM, respectively. LY233569 also inhibited
      (IC50 approximately 1.8 microM) zymosan-stimulated production of leukotriene B4
      in canine whole blood but had little or no concomitant effect on the production
      of thromboxane B2. Concentrations of LY233569 as high as 10 microM did not
      inhibit production or scavenge superoxide from activated human neutrophils. In
      normal anesthetized dogs, infusion of LY233569 (0.11 mg/kg/min, i.v.) for 6 hr
      produced persistent inhibition (approximately 80%) of leukotriene B4 production
      in blood challenged ex vivo with zymosan; the plasma concentration (approximately
      4 microM) of LY233569 was consistent with in vitro data illustrating selective
      and maximal inhibition of 5-LPO. In subsequent experiments, myocardial infarct
      size was measured after 1 hr of occlusion of the circumflex coronary artery and 5
      hr of reperfusion. Continuous infusion of LY233569 (0.11 mg/kg/min, i.v.) had
      little or no effect on base-line systolic arterial pressure, cardiac rate and the
      pressure rate product when compared with time-related changes observed in control
      dogs. LY233569 infusion also did not alter the degree of ST-segment deviation or
      the intensity and duration of cardiac arrhythmias associated with coronary artery
      occlusion and reperfusion. Resultant myocardial infarct sizes were 45 +/- 5% of
      the left ventricle placed at risk in control dogs and 43 +/- 4% in dogs given
      LY233569. Myeloperoxidase activity of infarcted myocardium did not differ between
      groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1988672
TI  - A new method for building protein conformations from sequence alignments with
      homologues of known structure.
AB  - We describe a largely automatic procedure for building protein structures from
      sequence alignments with homologues of known structure. This procedure uses
      simple rules by which multiple sequence alignments can be translated into
      distance and chirality constraints, which are then used as input for distance
      geometry calculations. By this means one obtains an ensemble of conformations for
      the unknown structure that are compatible with the rules employed, and the
      differences among these conformations provide an indication of the reliability of
      the structure prediction. The overall approach is demonstrated here by applying
      it to several Kazal-type trypsin inhibitors, for which experimentally determined
      structures are available. On the basis of our experience with these test
      problems, we have further predicted the conformation of the human pancreatic
      secretory trypsin inhibitor, for which no experimentally determined structure is
      presently available.

PMID- 1988673
TI  - Crystallization and preliminary X-ray diffraction studies of a MAT alpha 2-DNA
      complex.
AB  - Crystals have been obtained of the DNA-binding domain of the yeast MAT alpha 2
      repressor bound to a 21 base-pair DNA site. The crystals are grown from
      polyethylene glycol and CaCl2 and form in space group P2(1) with a = 60.1 A, b =
      39.4 A, c = 68.7 A and beta = 98 degrees. They diffract to 2.9 A resolution and
      contain one protein-DNA complex in the crystallographic asymmetric unit.

PMID- 1988674
TI  - Nuclear magnetic resonance studies of the hammerhead ribozyme domain. Secondary
      structure formation and magnesium ion dependence.
AB  - Proton nuclear magnetic resonance (n.m.r.) experiments were used to probe base
      pair formation in several hammerhead RNA enzyme (ribozyme) domains. The
      hammerhead domains consist of a 34 nucleotide ribozyme bound to a complementary
      13 nucleotide non-cleavable DNA substrate. Three hammerhead domains were studied
      that differ in the sequence and stability of one of the helices involved in
      recognition of the substrate by the ribozyme. The n.m.r. data show a 1:1
      stoichiometry for the ribozyme-substrate complexes. The imino proton resonances
      in the hammerhead complexes were assigned by two-dimensional nuclear Overhauser
      effect experiments. These data confirm the presence of two of the three helical
      regions in the hammerhead domain, predicted from phylogenetic data; and are also
      consistent with the formation of the third helix. Since a divalent cation is
      required for efficient catalytic activity of the hammerhead domain, the magnesium
      ion dependence of the n.m.r. spectra was studied for two of the hammerhead
      complexes. One of the complexes showed very large spectral changes upon addition
      of magnesium ions. However, the complex that has the most C.G base-pairs in one
      of the recognition helices shows essentially no spectral (and therefore
      presumably structural) changes upon addition of magnesium. These data are
      consistent with a model where the magnesium binding site already exists in the
      magnesium-free complex, suggesting that the magnesium ion serves primarily a
      catalytic, and not a structural, role under the conditions used here.

PMID- 1988675
TI  - Structure, function and properties of antibody binding sites.
AB  - Do antibody combining sites possess general properties that enable them to bind
      different antigens with varying affinities and to bind novel antigens? Here, we
      address this question by examining the physical and chemical characteristics most
      favourable for residues involved in antigen accommodation and binding.
      Amphipathic amino acids could readily tolerate the change of environment from
      hydrophilic to hydrophobic that occurs upon antibody-antigen complex formation.
      Residues that are large and can participate in a wide variety of van der Waals'
      and electrostatic interactions would permit binding to a range of antigens. Amino
      acids with flexible side-chains could generate a structurally plastic region,
      i.e. a binding site possessing the ability to mould itself around the antigen to
      improve complementarity of the interacting surfaces. Hence, antibodies could bind
      to an array of novel antigens using a limited set of residues interspersed with
      more unique residues to which greater binding specificity can be attributed. An
      individual antibody molecule could thus be cross-reactive and have the capacity
      to bind structurally similar ligands. The accommodation of variations in
      antigenic structure by modest combining site flexibility could make an important
      contribution to immune defence by allowing antibody binding to distinct but
      closely related pathogens. Tyr and Trp most readily fulfil these catholic
      physicochemical requirements and thus would be expected to be common in combining
      sites on theoretical grounds. Experimental support for this comes from three
      sources, (1) the high frequency of participation by these amino acids in the
      antigen binding observed in six crystallographically determined antibody-antigen
      complexes, (2) their frequent occurrence in the putative binding regions of
      antibodies as determined from structural and sequence data and (3) the potential
      for movement of their side-chains in known antibody binding sites and model
      systems. The six bound antigens comprise two small different haptens, non
      overlapping regions of the same large protein and a 19 amino acid residue
      peptide. Out of a total of 85 complementarity determining region positions, only
      37 locations (plus 3 framework) are directly involved in antigen interaction. Of
      these, light chain residue 91 is utilized by all the complexes examined, whilst
      light chain 32, light chain 96 and heavy chain 33 are employed by five out of the
      six. The binding sites in known antibody-antigen complexes as well as the
      postulated combining sites in free Fab fragments show similar characteristics
      with regard to the types of amino acids present. The possible role of other amino
      acids is also assessed.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1988676
TI  - Crystal structure of a Kunitz-type trypsin inhibitor from Erythrina caffra seeds.
AB  - The trypsin inhibitor DE-3 from Erythrina caffra (ETI) belongs to the Kunitz-type
      soybean trypsin inhibitor (STI) family and consists of 172 amino acid residues
      with two disulphide bridges. The amino acid sequence of ETI shows high homology
      to other trypsin inhibitors from the same family but ETI has the unique ability
      to bind and inhibit tissue plasminogen activator. The crystal structure of ETI
      has been determined using the method of isomorphous replacement and refined using
      a combination of simulated annealing and conventional restrained least-squares
      crystallographic refinement. The refined model includes 60 water molecules and
      166 amino acid residues, with a root-mean-square deviation in bond lengths from
      ideal values of 0.016 A. The crystallographic R-factor is 20.8% for 7770
      independent reflections between 10.0 and 2.5 A. The three-dimensional structure
      of ETI consists of 12 antiparallel beta-strands joined by long loops. Six of the
      strands form a short antiparallel beta-barrel that is closed at one end by a
      "lid" consisting of the other six strands coupled in pairs. The molecule shows
      approximate 3-fold symmetry about the axis of the barrel, with the repeating unit
      consisting of four sequential beta-strands and the connecting loops. Although
      there is no sequence homology, this same fold is present in the structure of
      interleukin-1 alpha and interleukin-1 beta. When the structure of ETI and
      interleukin-1 beta are superposed, the close agreement between the alpha-carbon
      positions for the beta-strands is striking. The scissile bond (Arg63-Ser64) is
      located on an external loop that protrudes from the surface of the molecule and
      whose architecture is not constrained by secondary structure elements, disulphide
      bridges or strong electrostatic interactions. The hydrogen bonds made by the side
      chain amide group of Asn12 play a key role in maintaining the three-dimensional
      structure of the loop. This residue is in a position corresponding to that of a
      conserved asparagine in the Kazal inhibitor family. Although the overall
      structure of ETI is similar to the partial structure of STI, the scissile bond
      loop is displaced by about 4 A. This displacement probably arises from the fact
      that the structure of STI has been determined in a complex with trypsin but could
      possibly be a consequence of the close molecular contact between Arg63 and an
      adjacent molecule in the crystal lattice.

PMID- 1988677
TI  - Structure of the B-DNA decamer C-C-A-A-C-G-T-T-G-G and comparison with
      isomorphous decamers C-C-A-A-G-A-T-T-G-G and C-C-A-G-G-C-C-T-G-G.
AB  - The crystal structure of the DNA decamer C-C-A-A-C-G-T-T-G-G has been solved to a
      resolution of 1.4 A, and is compared with the 1.3 A structure of C-C-A-A-G-A-T-T
      G-G and the 1.6 A structure of C-C-A-G-G-C-C-T-G-G. All three decamers
      crystallize isomorphously in space group C2 with five base-pairs per asymmetric
      unit, and with decamer double helices stacked atop one another along the c axis
      in a manner that closely approximates a continuous B helix. This efficient
      stacking probably accounts for the high resolution of the crystal data.
      Comparison of the three decamers reveals the following. (1) Minor groove width is
      more variable than heretofore realized. Regions of A.T base-pairs tend to be
      narrower than average, although two successive A.T base-pairs alone may not be
      sufficient to produce narrowing. The minor groove is wider in regions where BII
      phosphate conformations are opposed diagonally across the groove. (2) Narrow
      regions of minor groove exhibit a zig-zag spine of hydration, as was first seen
      in C-G-C-G-A-A-T-T-C-G-C-G, whereas wide regions show two ribbons of water
      molecules down the walls, connecting base edge N or O with sugar O-4' atoms.
      Regions of intermediate groove width may accommodate neither pattern of hydration
      well, and may exhibit a less regular pattern of hydration. (3) Base-pair stacking
      is virtually identical at equivalent positions in the three decamers. The
      unconnected step from the top of one decamer helix to the bottom of the next
      helix is a normal helix step in all respects, except for the absence of
      connecting phosphate groups. (4) BII phosphate conformation require the
      unstacking of the two bases linked by the phosphate, but do not necessarily
      follow as an inevitable consequence of unstacking. They have an influence on
      minor groove width as noted in point (1) above. (5) Sugar ring pseudorotation P
      and main-chain torsion angle delta show an excellent correlation as given by the
      equation: delta = 40 degrees cos (P + 144 degrees) + 120 degrees. Although
      centered around C-2'-endo, the conformations in these B-DNA helices are
      distributed broadly from C-3'-exo to O-4'-endo, unlike the tighter clustering
      around C-3'-endo observed in A-DNA oligomer structures.

PMID- 1988678
TI  - Analysis of local helix geometry in three B-DNA decamers and eight dodecamers.
AB  - Local variations in B-DNA helix structure are compared among three decamers and
      eight dodecamers, which contain examples of all ten base-pair step types. All
      pairwise combinations of helix parameters are compared by linear regression
      analysis, in a search for internal relationships as well as correlations with
      base sequence. The primary conclusions are: (1) Three-center hydrogen bonds
      between base-pairs occur frequently in the major groove at C-C, C-A, A-A and A-C
      steps, but are less convincing at C-C and C-T steps in the minor groove. The
      requirements for large base-pair propeller are (1) that the base-pair should be
      A.T rather than G.C, and (2) that it be involved in a major groove three-center
      hydrogen bond with the following base-pair. Either condition alone is
      insufficient. Hence, a large propeller is expected at the leading base-pair of A
      A and A-C steps, but not at A-T, T-A, C-A or C-C steps. (2) A systematic and
      quantitative linkage exists between helix variables twist, rise, cup and roll, of
      such strength that the rise between base-pairs can hardly be described as an
      independent variable at all. Two typical patterns of behavior are observed at
      steps from one base-pair to the next: high twist profile (HTP), characterized by
      high twist, low rise, positive cup and negative roll, and low twist profile
      (LTP), marked by low twist, high rise; negative cup and positive roll. Examples
      of HTP are steps G-C, G-A and Y-C-A-R, where Y is pyrimidine and R is purine.
      Examples of LTP steps are C-G, G-G, A-G and C-A steps other than Y-C-A-R. (3) The
      minor groove is especially narrow across the two base-pairs of the following
      steps: A-T, T-A, A-A and G-A. (4) In general, base step geometry cannot be
      correlated solely with the bases that define the step in question; the two
      flanking steps also must be taken into account. Hence, local helix structure must
      be studied in the context, not of two base-pairs: A-B, but of four: x-A-B-y.
      Calladine's rules, although too simple in detail, were correct in defining the
      length of sequence over which a given perturbation is expressed. Whereas ten
      different two-base steps are possible, allowing for the identity of complementary
      sequences, there are 136 different four-base steps. Only 33 of these 136 four
      base steps are represented in the decamer and dodecamer structures solved to
      date, and hence it is premature to try to set up detailed structural algorithms.
      (5) The sugar-phosphate backbone chains of B-DNA place strong limits on sequence
      induced structural variation, damping down most variables within four or five
      base-pairs, and preventing purine-purine anti-anti mismatches from causing bulges
      in the double helix. Hence, although short-range sequence-induced deformations
      (or deformability) are observed, long-range deformations propagated down the
      helix are not to be expected.

PMID- 1988680
TI  - Monomers of the Escherichia coli SSB-1 mutant protein bind single-stranded DNA.
AB  - The Escherichia coli wild-type single strand binding (SSB) protein is a stable
      tetramer that binds to single-stranded (ss) DNA in its role in DNA replication,
      recombination and repair. The ssb-1 mutation, a substitution of tyrosine for
      histidine-55 within the SSB-1 protein, destabilizes the tetramer with respect to
      monomers, resulting in a temperature-sensitive defect in a variety of DNA
      metabolic processes, including replication. Using quenching of the intrinsic SSB
      1 tryptophan fluorescence, we have examined the equilibrium binding of the
      oligonucleotide, dT(pT)15, to the SSB-1 protein in order to determine whether a
      ssDNA binding site exists within individual SSB-1 monomers or whether the
      formation of the SSB tetramer is necessary for ssDNA binding. At high SSB-1
      protein concentrations, such that the tetramer is stable, we find that four
      molecules of dT(pT)15 bind per tetramer in a manner similar to that observed for
      the wild-type SSB tetramer; i.e. negative co-operativity is observed for ssDNA
      binding to the SSB-1 protomers. As a consequence of this negative co-operativity,
      binding is biphasic, with two molecules of dT(pT)15 binding to the tetramer in
      each phase. However, the intrinsic binding constant, K16, for the SSB-1 protomer
      dT(pT)15 interaction is a factor of 3 lower than for the wild-type protomer
      interaction and the negative co-operativity parameter, sigma 16, is larger in the
      case of the SSB-1 tetramer, indicating a lower degree of negative co-operativity.
      At lower SSB-1 concentrations, SSB-1 monomers bind dT(pT)15 without negative co
      operativity; however, the intrinsic affinity of dT(pT)15 for the monomer is a
      factor of approximately 10 lower than for the protomer (50 mM-NaCl, pH 8.1, 25
      degrees C). Therefore, an individual SSB-1 monomer does possess an independent
      ssDNA binding site; hence formation of the tetramer is not required for ssDNA
      binding, although tetramer formation does increase the binding affinity
      significantly. These data also show that the negative co-operativity among ssDNA
      binding sites within an SSB tetramer is an intrinsic property of the tetramer. On
      the basis of these studies, we discuss a modified explanation for the temperature
      sensitivity of the ssb-1 phenotype.

PMID- 1988679
TI  - Recognition of unusual DNA structures by human DNA (cytosine-5)methyltransferase.
AB  - The symmetry of the responses of the human DNA (cytosine-5)methyltransferase to
      alternative placements of 5-methylcytosine in model oligodeoxynucleotide duplexes
      containing unusual structures has been examined. The results of these experiments
      more clearly define the DNA recognition specificity of the enzyme. A simple three
      nucleotide recognition motif within the CG dinucleotide pair can be identified in
      each enzymatically methylated duplex. The data can be summarized by numbering the
      four nucleotides in the dinucleotide pair thus: 1 4/2 3. With reference to this
      numbering scheme, position 1 can be occupied by cytosine or 5-methylcytosine;
      position 2 can be occupied by guanosine or inosine; position 3, the site of
      enzymatic methylation, can be occupied only by cytosine; and position 4 can be
      occupied by guanosine, inosine, O6-methylguanosine, cytosine, adenosine, an
      abasic site, or the 3' hydroxyl group at the end of a gapped molecule. Replacing
      the guanosine normally found at position 4 with any of the moieties introduces
      unusual (non-Watson-Crick) pairing at position 3 and generally enhances
      methylation of the cytosine at that site. The exceptional facility of the enzyme
      in actively methylating unusual DNA structures suggests that the evolution of the
      DNA methyltransferase, and perhaps DNA methylation itself, may be linked to the
      biological occurrence of unusual DNA structures.

PMID- 1988681
TI  - Differentiation-dependent alteration in the chromatin structure of chromosomal
      protein HMG-17 gene during erythropoiesis.
AB  - The expression of the gene coding for chromosomal protein HMG-17 is down
      regulated during chicken erythrocyte maturation. The transcriptional down
      regulation is associated with major alterations in the chromatin structure of
      this gene. The 5' region of the gene contains both constitutive and developmental
      stage-specific deoxyribonuclease I (DNase I) hypersensitive sites. The
      constitutive sites bracket the "CpG island" present in the gene, which remains
      hypomethylated throughout the various developmental stages. During
      erythropoiesis, the gene acquires a distinct structure that, upon digestion with
      micrococcal nuclease (MNase) yields an unusual repeat. Two nucleosomes, with a
      200 base-pair repeat, are positioned immediately downstream from the start of
      transcription. Immediately downstream and upstream from these nucleosomes, the
      boundaries between MNase sites change to a 75 base-pair repeat, which indicates
      an unusual chromatin structure. The differentiation related changes in the DNase
      I and MNase digestion pattern in the 5' region of the gene suggest that sequences
      present in the first intron may be involved in gene regulation. The results may
      be relevant to the regulation of the entire HMG-14/-17 gene family.

PMID- 1988682
TI  - Regulation of histone H1(0) accumulation during induced differentiation of murine
      erythroleukemia cells.
AB  - Histone H1(0) is one of the potential candidates that may contribute to the onset
      and stabilization of a genetic program during induced differentiation of murine
      erythroleukemia cells. In an attempt to understand better the role of H1(0) in
      this process we have tried to determine at which level the regulation of its
      induced accumulation occurs. Protein H1(0) was found to increase by a factor of 3
      while its mRNA increased by a factor of 14, due to activation of gene
      transcription. As shown by H1(0) half-life measurements, the difference between
      the actual amount of H1(0) and that expected from the amount of mRNA was not due
      to increased turnover of the protein. Fractionation of the translational
      apparatus at several times during induction, revealed that H1(0) mRNA was
      efficiently transferred to the high molecular weight polysomes. The rate of
      synthesis of H1(0) was also increased by a factor of 4. Taken together, these
      results suggest the existence of a strong control at the translational level,
      which regulates H1(0) accumulation.

PMID- 1988683
TI  - Structural analysis of the peptidyl transferase region in ribosomal RNA of the
      eukaryote Xenopus laevis.
AB  - Accessible single-strand bases in Xenopus laevis 28 S ribosomal RNA (rRNA) Domain
      V, the peptidyl transferase region, were determined by chemical modification with
      dimethylsulfate, 1-cyclohexyl-3-(2-morpholinoethyl-carbodiimide metho-p-toluene
      sulfonate and kethoxal, followed by primer extension. The relative
      accessibilities of three rRNA substrates were compared: deproteinized 28 S rRNA
      under non-denaturing conditions (free 28 S rRNA), 60 S subunits and 80 S
      ribosomes. Overall, our experimental results support the theoretical secondary
      structure model of Domain V derived by comparative sequence analysis and
      compensatory base-pair changes, and support some theoretical tertiary
      interactions previously suggested by covariation. The 60 S subunits and 80 S
      ribosomes generally show increasing resistance to chemical modification. Bases
      which are sensitive in free 28 S rRNA but protected in 60 S subunits may be sites
      for ribosomal protein binding or induced structural rearrangements. Another class
      of nucleotides is distinguished by its sensitivity in 60 S subunits but
      protection in 80 S ribosomes; these nucleotides may be involved in subunit
      subunit interactions or located at the interface of the ribosome. We found a
      third class of bases, which is protected in free 28 S rRNA but sensitive in 60 S
      subunits and/or 80 S ribosomes, suggesting that structural changes occur in
      Domain V as a result of subunit assembly and ribosome formation. One such region
      is uniquely hypersensitive in eukaryotic ribosomes but is absent in Escherichia
      coli ribosomes. Sites that we determined to be accessible on empty 80 S ribosomes
      could serve as recognition sites for translation components.

PMID- 1988684
TI  - Systemic toxic effects associated with high-dose verapamil infusion and
      chemotherapy administration.
AB  - Aside from its more conventional uses as a cardiovascular drug, the calcium
      channel blocker verapamil has recently been added to chemotherapeutic regimens to
      reduce drug resistance in B-cell and other neoplasms that express the P
      glycoprotein. We recently treated patients with continuous-infusion verapamil
      (0.15 mg/kg per hour to 0.60 mg/kg per hour) over a 5-day period in combination
      with continuous-infusion vincristine and doxorubicin plus oral dexamethasone.
      Seventy-one courses involving 35 hospitalized patients were prospectively studied
      for cardiovascular and other side effects. Cardiovascular side effects were
      observed most frequently and consisted of first-degree heart block, hypotension,
      sinus bradycardia, and junctional rhythms. We observed higher degree heart block,
      but the QRS interval remained narrow and the ventricular escape rate remained
      relatively normal. Effects on mean arterial pressure, heart rate, and PR interval
      were both time and dose related. Severe, symptomatic congestive heart failure was
      rarely observed. The most common noncardiovascular side effects were
      constipation, peripheral edema, and weight gain. All systemic toxic effects
      observed were easily treated or disappeared with either temporary or permanent
      discontinuation of the verapamil infusion or by a decrease in the dose of
      verapamil. We conclude that the cardiovascular side effects associated with
      continuous, high-dose intravenous verapamil therapy are significant and dose
      limiting but are rapidly reversible. Less cardiotoxic chemosensitizers are needed
      to reverse multidrug resistance in cancer.

PMID- 1988685
TI  - Effects of in vitro electrical stimulation on enhancement and suppression of
      malignant lymphoma cell proliferation.
AB  - The suppression and enhancement of proliferation of mouse EL4 lymphoma cells
      varied significantly when the cells were electrically stimulated within a narrow
      range of low-level direct current. With the use of platinum electrodes, the
      suppression characteristics were observed over a narrow range, or window, of
      direct currents centered at approximately 17 microA. Enhancement characteristics
      were observed over a broad range of low-level direct currents (approximately 0.1
      to 10 microA). These results indicate that the proliferation of certain
      eukaryotic cells may be directly controlled by stimulation with low-level direct
      current.

PMID- 1988686
TI  - Effect of interleukin-1-beta on metastasis formation in different tumor systems.
AB  - Experiments were done to determine the effect of interleukin-1-beta (IL-1 beta)
      on metastasis formation in different tumor systems. Intravenous administration of
      1 microgram of human recombinant IL-1 beta given 1 hour before tumor cell
      injection augmented lung colony formation (experimental metastases) by the human
      A375 melanoma variants, the human HT-29M colon carcinoma, the SN12-K1 renal
      carcinoma in nude mice, the murine B16 melanoma variants, and the murine UV-2237M
      fibrosarcoma in syngeneic recipients. The same treatment did not induce lung
      colony formation by a human rectal carcinoma (HCC-P2988) or by a murine reticulum
      cell sarcoma (M5076), both of which are not metastatic to the lung. Spontaneous
      metastases were studied in C57BL/6 mice bearing the B16-BL6 melanoma (metastatic
      to the lung) in their footpad and the M5076 reticulum cell sarcoma (metastatic to
      the liver) subcutaneously. Daily intraperitoneal treatment with 1 microgram of IL
      1 beta increased lung and liver metastases. These findings indicate that
      treatment of mice with IL-1 beta can increase the number of artificial or
      spontaneous metastases and that this effect is not limited to a single tumor type
      or to a specific organ.

PMID- 1988687
TI  - Hemorrhagic gastritis as a new dose-limiting toxicity of recombinant tumor
      necrosis factor.

PMID- 1988688
TI  - Maize and risk of cancers of the oral cavity, pharynx, and esophagus in
      northeastern Italy.

PMID- 1988689
TI  - Pilot study of cimetidine in the treatment of Kaposi's sarcoma in patients with
      acquired immunodeficiency syndrome.

PMID- 1988690
TI  - Challenges to the therapy of cancer with monoclonal antibodies.

PMID- 1988691
TI  - 1971-1991: Science unlocks cancer cell secrets.

PMID- 1988692
TI  - Patient accrual is up for high-priority trials.

PMID- 1988693
TI  - Atlas maps cancer mortality among nonwhites.

PMID- 1988694
TI  - Tumor suppressor genes: new prospects for cancer research.
AB  - Cancer is thought to arise from the accumulation of several genetic mutations in
      a single cell. Until recently, the only tumorigenic mutations that have been
      studied in detail are those that activate oncogenes. The discovery of tumor
      suppressor genes, for which inactivating mutations elicit tumorigenesis, has
      added a new dimension to our understanding of neoplasia. The retinoblastoma
      susceptibility gene RB is the prototype tumor suppressor gene and has been shown
      to suppress the transformed phenotype for several different cancers. Additional
      studies have revealed other tumor suppressor genes that may operate in a variety
      of tissues through a variety of mechanisms. These mechanisms may regulate the
      choice between cellular proliferation and differentiation and appear to involve
      such processes as the initiation of DNA replication, regulation of expression of
      certain genes, intercellular communication and adhesion, and the transduction of
      external signals to intracellular effectors. The elucidation of these mechanisms
      will enhance our understanding of both oncogenesis and the fundamental operations
      of the cell.

PMID- 1988695
TI  - Phase I and imaging trial of indium 111-labeled anti-epidermal growth factor
      receptor monoclonal antibody 225 in patients with squamous cell lung carcinoma.
AB  - Murine monoclonal antibody (MAb) 225 (IgG1) against the epidermal growth factor
      (EGF) receptor competitively blocks EGF binding and inhibits EGF-induced
      activation of receptor tyrosine kinase and cell proliferation. The effect of MAb
      225 was studied in a phase I trial in patients with inoperable squamous cell
      carcinoma of the lung, which invariably expresses high levels of EGF receptors.
      Groups of three patients received total doses of MAb 225 ranging from 1 mg to 300
      mg. Except at the lowest dose, each infusion included 4 mg of indium 111 (111In)
      labeled MAb 225. No toxicity was observed. Tumors were imaged in all patients who
      received doses of 20 mg or greater. Presumed metastases greater than or equal to
      1 cm in diameter were imaged with doses of 40 mg or greater. Single-photon
      emission-computed tomography could be carried out at the 120-mg and 300-mg doses
      and significantly improved tumor visualization. All patients produced anti-murine
      antibodies. We conclude that treatment with an MAb that inhibits EGF receptor
      function is safe at the doses and schedule studied. 111In-labeled MAb images
      squamous cell lung carcinoma; tumor uptake of the labeled MAb is dose dependent.
      Further studies are warranted to explore the potential therapeutic efficacy of
      anti-EGF receptor MAbs and other agents that act in a comparable manner.

PMID- 1988696
TI  - Breast cancer prognostic factors: evaluation guidelines.

PMID- 1988697
TI  - Hypoxia revisited.

PMID- 1988699
TI  - Cancer prevention: out of the shadows and into the cell.

PMID- 1988698
TI  - p53: how a tumor suppressor works.

PMID- 1988700
TI  - Electromagnetic fields and cancer--media and public attention affect research.

PMID- 1988701
TI  - Policy gains speed America's flight from tobacco.

PMID- 1988703
TI  - Therapeutic advantage of hypoxic cells in tumors: a theoretical study.
AB  - The presence of hypoxic cells in solid tumors has long been considered a problem
      in cancer treatment, particularly for radiation therapy but also for treatment
      with some anticancer drugs. Three general strategies are being actively explored
      to overcome the problem: oxygenating the tumor, sensitizing the hypoxic cells to
      radiation (or chemotherapy), or killing the hypoxic cells (with a hypoxic cell
      cytotoxin). In the present study, we have examined the impact of each of these
      three strategies on a standard radiation therapy regimen (30 doses of 2 Gy),
      using either of two major assumptions: full reoxygenation or no reoxygenation of
      the tumor cells. We demonstrate that a hypoxic cell cytotoxin can produce a level
      of tumor cell killing higher (by several orders of magnitude) than that produced
      by full oxygenation of a tumor or by use of an optimum hypoxic cell
      radiosensitizer, provided the cytotoxin kills more than approximately 50% of the
      hypoxic cells each time it is given. The only assumption that makes a difference
      is whether reoxygenation occurs: In the worst case (ie, no reoxygenation), the
      hypoxic cell cytotoxin performs only as well as an optimum radiosensitizer. The
      analysis shows that hypoxic cells in tumors can be a major therapeutic advantage.
      Therefore, we recommend that research efforts be concentrated on development of
      superior hypoxic cell cytotoxins rather than improved hypoxic cell
      radiosensitizers and that, in parallel, emphasis be placed on development of
      agents to increase hypoxia.

PMID- 1988702
TI  - Stress response protein (srp-27) determination in primary human breast
      carcinomas: clinical, histologic, and prognostic correlations.
AB  - Expression of an estrogen-regulated protein known as the 27,000-d heat-shock or
      stress-response protein (srp-27) was evaluated in human breast carcinomas and
      established breast cancer cell lines. Results obtained by Northern and Western
      blot analyses and immunohistochemical methods were concordant.
      Immunohistochemical assessment of srp-27 expression in 300 breast carcinomas
      (with median patient follow-up of 8 years) was performed. Twenty-six percent of
      lymph node-negative and 45% of lymph node-positive tumors were overexpressors.
      Univariate analysis demonstrated significant correlations between srp-27
      overexpression and estrogen receptor (ER) content, pS2 protein expression, nodal
      metastases, advanced T stage, lymphatic/vascular invasion, and a shorter disease
      free survival period (but not a shorter overall survival) for the study
      population as a whole. Regression tree analysis showed that srp-27 expression was
      an independent prognostic indicator for disease-free survival only in patients
      with one to three positive lymph nodes. The Cox proportional hazards model
      confirmed the independent prognostic significance of nodal involvement, T stage,
      and ER content but failed to recognize srp-27 overexpression as a significant
      independent parameter predictive of patient outcome in the patient population as
      a whole. The observed associations between srp-27 overexpression and more
      aggressive tumors suggest a biologic role for srp-27 in human breast carcinomas.

PMID- 1988704
TI  - Analysis of alterations in the retinoblastoma gene and tumor grade in bone and
      soft-tissue sarcomas.
AB  - We examined 43 sporadic bone and soft-tissue sarcomas for molecular genetic
      alterations affecting the retinoblastoma susceptibility gene Rb-1 (also known as
      RB1). The gene was altered in 6 of 14 sporadic osteosarcomas and in 5 of 29 other
      bone and soft-tissue sarcomas. Rb-1 messenger RNA (mRNA) transcripts were
      detected in normal tissues and benign lipomas, but they were absent or altered in
      each of the 19 sarcomas we examined. To examine the association of deletions in
      the Rb-1 gene with tumor grade, we correlated the DNA alterations in the Rb-1
      gene with clinical data for 36 patients. The Rb-1 gene was altered in 40% of high
      grade bone and soft-tissue tumors, but not in low-grade bone tumors and in only
      one low-grade, soft-tissue sarcoma. Overall, 10 of 25 high-grade sarcomas had
      detectable alterations of the Rb-1 gene compared with only 1 of 11 low-grade
      tumors.

PMID- 1988705
TI  - Diffusion and binding of monoclonal antibody TNT-1 in multicellular tumor
      spheroids.
AB  - Tumor spheroids of HT-29 human colon adenocarcinoma and A375 melanoma were
      established to investigate the uptake and clearance kinetics of TNT-1, a
      monoclonal antibody that targets necrotic cells of tumors. Our data reveal that
      there was rapid uptake of TNT-1 and its F(ab')2 fragment in both spheroid models,
      whereas an antibody of irrelevant specificity, Lym-1, and its F(ab')2 fragment
      bound poorly to the spheroids. Unlike previously reported monoclonal antibodies
      to tumor cell-surface antigens, TNT-1 showed 1) a linear uptake that increased
      over time without saturation in tumor spheroids and 2) an unexpected uptake by a
      subpopulation of cells in the viable outer rim of the spheroids. These
      preclinical studies provide important information concerning the therapeutic
      potential of TNT monoclonal antibodies for the treatment of cancer and
      micrometastases.

PMID- 1988706
TI  - Rapid functional assay for multidrug resistance in human tumor cell lines using
      the fluorescent indicator fluo-3.

PMID- 1988707
TI  - Psychodynamics of late diagnosis cancer patients.

PMID- 1988708
TI  - The danger of unrecognized cancer treatment clinics.

PMID- 1988709
TI  - Ureteral obstruction and ureteral fistulas after aortofemoral or aortoiliac
      bypass surgery.
AB  - Ureteral injury after aortofemoral or aortoiliac bypass surgery has seldom been
      described in the literature considering the large number of bypass operations
      performed. Some causative factors, such as the position of the bypass, are
      obvious while others are less clear. However, no attempt has been made to unify
      criteria to establish a management protocol. Of 154 cases of ureteral units with
      ectasia reviewed ureteral fistulas were present in 19. Radiological ureteral
      obstruction appears to precede fistula formation. Symptoms, time of diagnosis and
      treatment according to the predominant etiology have been discussed. Etiological
      (in varying degrees of importance), clinical and diagnostic criteria, together
      with a management and therapeutic protocol in which early and late lesions are
      clearly differentiated were established, while bearing in mind that not all
      radiological obstruction patterns correspond to true ureteral lesions.

PMID- 1988710
TI  - Management of primary nonrenal parenchymal malignancies with vena caval thrombus.
AB  - We report our experience with the management of 7 primary nonrenal parenchymal
      malignancies with vena caval tumor thrombus. Included are 3 cases of adrenal
      cortical carcinoma and 1 each of transitional cell carcinoma, embryonal cell
      testicular carcinoma, pheochromocytoma and primary small cell carcinoma of the
      lung with metastases to the kidney. Surgical treatment and followup are
      presented, as well as a review of the literature. An aggressive surgical approach
      is warranted because prolonged survivals free of disease are possible.

PMID- 1988711
TI  - The incidence and prognostic significance of humoral hypercalcemia in renal cell
      carcinoma.
AB  - This retrospective study was conducted to evaluate the incidence and prognostic
      significance of humoral hypercalcemia in 218 renal cell carcinoma patients during
      the last 20 years. Of 218 patients 20 (9.2%) were hypercalcemic, with serum
      calcium levels ranging from 10.7 to 16.0 mg./dl. The respective incidence of
      humoral hypercalcemia was 3% in patients with stage I, 5.9% with stage II, 14.1%
      with stage III and 18.9% with stage IV disease without bone metastasis. The
      survival curves between the hypercalcemic and eucalcemic groups among stages I to
      III cancer patients showed no statistical significance (p greater than 0.05). The
      survival curve deteriorated significantly in stage IV cancer patients with
      humoral hypercalcemia (p less than 0.005), with a median survival of 45.0 +/-
      39.7 days versus 286.4 +/- 27.6 days in eucalcemic patients. No specific
      correlation was found between pathological cell type and humoral hypercalcemia.

PMID- 1988712
TI  - Post-transplant renal artery stenosis: a possible immunological phenomenon.
AB  - A retrospective review of 110 consecutive kidney transplants performed during 4
      years revealed the development of renal artery stenosis in 9 patients (8.18%). A
      comparison of this group with a control group similar in patient age and interval
      elapsed since transplantation revealed no significant differences in donor and
      recipient ages, degree of HLA compatibility or serum creatinine levels. However,
      there was a significant difference in the number of acute rejection episodes. In
      our series only male patients were affected. A sizable proportion of the patients
      (50%) had no detectable murmur over the graft area despite high blood pressure
      and increased creatinine levels. The absence of surgical injury during extraction
      and implantation of the grafts, together with the anatomical site of the stenosis
      and correlation with the degree of immunological intolerance suggest an
      immunological factor as the underlying cause in post-transplant renal artery
      stenosis.

PMID- 1988713
TI  - Acute changes in renal function following extracorporeal shock wave lithotripsy
      in patients with a solitary functioning kidney.
AB  - Twelve consecutive patients with a solitary functioning kidney were treated for
      renal stone by extracorporeal shock wave lithotripsy (ESWL*) with the modified
      Dornier HM3 lithotriptor and studied for 3 days after treatment. Urinary
      excretion of electrolytes, N-acetyl-beta-glucosaminidase (NAG), alkaline
      phosphatase, kallikrein, glycosaminoglycans, albumin and beta 2-microglobulin,
      and clearances of creatinine, inulin and para-aminohippuric acid were determined,
      as were serum levels of creatinine, urea, beta 2-microglobulin and aldosterone,
      and plasma renin activity. Urinary flow rate, free water clearance, and urinary
      excretion of NAG, kallikrein and beta 2-microglobulin were significantly
      increased 0 to 24 hours after ESWL. The urinary excretions of alkaline
      phosphatase, albumin and glycosaminoglycans were unchanged. Glomerular filtration
      rate was significantly decreased and effective renal plasma flow was unchanged.
      Filtration fraction was stable. Serum lactic dehydrogenase increased
      significantly after ESWL and remained high through the period of observation.
      Serum levels of creatinine, beta 2-microglobulin and aldosterone were unaltered.
      A decrease in plasma renin activity immediately after treatment is explained by
      the water immersion and the extracellular volume expansion during treatment.

PMID- 1988714
TI  - Use of the Collings knife electrode for percutaneous access in difficult
      endourology cases.
AB  - Percutaneous endourological techniques for the removal of upper urinary tract
      calculi and for the closed treatment of ureteropelvic junction obstruction are
      well described. These techniques are dependent on satisfactory percutaneous
      access and nephrostomy tract dilation. We used the Collings knife electrode for
      the creation of a nephrostomy tract in 17 patients (19 renal units) with
      difficult percutaneous access due to scarification, or the inability to advance a
      guide wire sufficiently for stabilization and dilation by conventional means. A
      nephrostomy tract was established successfully in all 19 procedures requiring an
      average of 12 minutes. Two major complications occurred that required blood
      transfusion and an open operation. Endourological treatment was successful in the
      remaining 17 cases. We believe that this technique provides an alternative to an
      open operation when standard access and dilation methods for endourological
      procedures are unsuccessful.

PMID- 1988715
TI  - Ureteral calculi: natural history and treatment in an era of advanced technology.
AB  - Patients with ureteral stones may be managed expectantly, or treated with a
      variety of invasive and noninvasive techniques depending on stone composition,
      size and location, expectations of the patient and experience of the surgeon. Of
      378 patients with documented ureteral calculi 60% passed the stones
      spontaneously. Passage rates from the proximal, middle and distal ureter were 22,
      46 and 71%, respectively. Basketing under fluoroscopic control of distal stones
      was successful in 79% of the attempts and for those in whom this approach failed
      ureteroscopy was performed, with a success rate of 90%. When ureteroscopy was
      used as the initial treatment of distal stones removal was achieved in 81% of the
      patients. These statistics serve as a reminder that traditional therapy of
      ureteral stones has not lost its role in contemporary practice.

PMID- 1988716
TI  - Management of upper tract calculi in patients with tubularized urinary
      diversions.
AB  - In a retrospective review of patients with urinary diversion who presented to our
      stone center during a 3.5-year period 9 underwent 20 procedures for suspected
      stone episodes. Eventual outcome was excellent in all but 1 patient. In
      particular, all attempts at retrograde trans-stomal manipulation were successful.
      We present our cases, and note the technical considerations and management
      principles. Frequently, these patients are best served by a combination of
      percutaneous antegrade, trans-stomal retrograde and/or extracorporeal shock wave
      lithotripsy.

PMID- 1988717
TI  - Metabolic alterations following continent urinary diversion through colonic
      segments.
AB  - This study examined acid-base metabolism in patients with continent colonic
      urinary diversions and compared them to a control population. Diverted patients
      demonstrated mild acidosis and a urinary acidification defect. Ammonium chloride
      loading failed to demonstrate any major differences in the ability of these
      patients to handle an acute acid challenge. Continent colonic urinary diversions
      do not appear to create significant acid-base changes in patients with normal
      hepatic and renal function.

PMID- 1988718
TI  - Uptake of 2-deoxy, 2-(18F) fluoro-D-glucose in bladder cancer: animal
      localization and initial patient positron emission tomography.
AB  - An orthotopically transplanted, locally metastasizing rat bladder tumor model was
      developed to evaluate the extent of uptake of fluoro-deoxy-glucose (FDG) in
      bladder cancer. Significant uptake of FDG in localized bladder tumors in rats was
      shown, with an average tumor-to-blood ratio of 39 at 2 hours after intravenous
      FDG administration. Metastases (3 nodal and 1 peritoneal) also showed significant
      uptake of FDG, with an average metastasis-to-blood ratio of 21.7, and tumor
      involved-to-normal lymph node ratio of 5.3. Because FDG is excreted in the urine,
      urinary FDG potentially could prevent the use of FDG/positron emission tomography
      (FDG/PET) scanning for localized bladder cancer. Bladder lavage successfully
      reduced the retention of FDG in the normal rat bladder, with an estimated uptake
      ratio of tumor-to-normal bladder of 13.1 after 5 ml. saline irrigation. Based on
      these data, we performed an FDG/PET scan of a patient with biopsy proved
      recurrent intravesical bladder cancer after radiation therapy. Computerized
      tomography (CT) of the pelvis showed abnormalities consistent with radiation
      scarring and extravesical tumor. Due to the scarring, the extent of tumor growth
      could not be determined. The patient also had pulmonary opacities seen on chest
      radiography. The FDG/PET scan of this patient showed significant extravesical
      uptake in the pelvis, confirming the abnormality noted on CT. Good images of the
      clinically apparent metastases in the chest also were obtained. These preliminary
      data indicate that FDG/PET imaging of bladder cancer is feasible and it may
      provide new information for the diagnosis and staging of patients with bladder
      cancer.

PMID- 1988719
TI  - Vacuum tumescence devices: the role of papaverine in the selection of patients.
AB  - We conducted a prospective study to determine the positive predictive value of
      papaverine testing to select patients in whom a vacuum constriction device would
      be a successful alternative to operative management of impotence. A total of 30
      men presenting to an impotence clinic was evaluated with a series of papaverine
      dosages up to 60 mg. These patients then received a physician-administered trial
      of a vacuum constriction device, followed by 3 months of home use and a repeat
      objective evaluation. Initial responses to the device were poor, with 46% of the
      patients (14) achieving a rigid erection. However, after 3 months of home use 83%
      of the patients (25) achieved a rigid erection. The positive predictive value of
      a good response to the papaverine trial was 94%.

PMID- 1988720
TI  - Male fertility in cyclosporine-treated renal transplant patients.
AB  - Fertility and potential fertility were evaluated in 9 young men on cyclosporine A
      therapy following renal transplantation. Semen analysis was normal in most
      parameters in 8 patients as was testicular hormonal function. Of 4 men who had
      attempted to impregnate their wives 3 succeeded. Cyclosporine A does not seem to
      affect adversely fertility in men.

PMID- 1988721
TI  - Recurrent subacute torsion: prospective study of effects on testicular morphology
      and function.
AB  - A prospective study was done on 43 consecutive patients with a diagnosis of
      recurrent subacute testicular torsion. All patients underwent full examination,
      hormonal assays and seminal fluid analysis before scrotal exploration, bilateral
      testicular biopsy and fixation. Seminal fluid analysis and hormonal assays were
      repeated 3 months postoperatively. Of the patients 36 were cured of recurrent
      pain, 35 of whom had a horizontally lying testis. No hormonal abnormalities were
      found preoperatively or postoperatively. Three patients had abnormal seminal
      fluid analysis. Testicular biopsies, including Johnsen scores, were abnormal in
      these 3 patients and normal in the other 33. It is concluded that patients with
      recurrent subacute torsion can be identified accurately and treated
      satisfactorily. There is little evidence that these patients suffer testicular
      damage as a result of this subacute torsion or that any pre-existing cellular
      abnormality exists to explain the oligospermia that frequently is seen in
      patients who have acute testicular torsion.

PMID- 1988722
TI  - Post-chemotherapy tumor residuals in patients with advanced nonseminomatous
      testicular cancer. Is it necessary to resect all residual masses?
AB  - A total of 15 patients with advanced nonseminomatous testicular cancer underwent
      2 sequential operations (4 in 1 patient) to remove residual masses after
      cisplatin-based combination chemotherapy. All patients had normal human chorionic
      gonadotropin and alpha-fetoprotein levels but persistent radiographic masses
      after chemotherapy. The operations included retroperitoneal lymph node dissection
      in 13 patients, thoracotomy in 15, hepatic resection in 3 and craniotomy in 1.
      Histological comparison of the specimens resected during post-chemotherapy
      operations 1 and 2 demonstrated different patterns in 7 of 15 patients. Of these
      7 patients 4 had less favorable pathological features in the specimen removed
      during the second procedure. Residual malignant tumor or mature teratoma was
      found in at least 1 site in 12 of the 15 patients and only 3 had complete
      necrosis or fibrosis in both specimens examined. These data indicate the
      favorable impact of excising all post-chemotherapy tumor residuals in patients
      with advanced nonseminomatous testicular cancer. However, in patients with no
      teratomatous elements in the testicular tumor and complete necrosis or fibrosis
      in the initial post-chemotherapy operation specimen the probability of complete
      necrosis or fibrosis in remaining tumors appears to be high.

PMID- 1988723
TI  - The distribution of residual cancer in radical prostatectomy specimens in stage A
      prostate cancer.
AB  - To assess the volume and distribution of residual cancer after transurethral
      resection of the prostate in stage A cancer patients 42 step-sectioned radical
      prostatectomy specimens were examined, and the volume, location, grade and
      extracapsular extension of the residual tumor were recorded. A total of 13
      patients had stage A1 tumors (5% or less tumor in the transurethral resection
      specimen and a Gleason sum of 7 or less) and 29 had stage A2 disease. Residual
      cancer was present in the radical prostatectomy specimen in 41 patients (98%)
      with a mean volume of 1.28 cc. The location of residual cancer, that is
      multifocal (76%), peripheral (81%) and distal to the verumontanum (66%), makes
      complete removal or even identification of residual tumor (restaging) by repeat
      transurethral resection improbable. Of the stage A1 cancer patients 4 (30%) had
      more than 1 cc residual tumor volume, extracapsular extension or seminal vesicle
      invasion. On the other hand, 14 of the stage A2 cancer patients (48%) had less
      than 1 cc residual tumor completely confined to the gland. Foci of residual
      cancer were found in the transition zone in 67% and in the peripheral zone in 90%
      of the patients. The grade of the residual peripheral zone cancer was
      significantly higher than that of the transition zone cancer in the same gland (p
      = 0.0004). Eight of 13 instances of extracapsular extension and all 5 of seminal
      vesicle invasion were directly attributable to peripheral zone cancer. These
      observations imply that the greatest threat to patients with stage A prostate
      cancer may be a separate, associated cancer in the peripheral zone rather than
      the primary transition zone cancer incidentally removed at transurethral
      resection.

PMID- 1988724
TI  - Bioavailability of potassium and magnesium, and citraturic response from
      potassium-magnesium citrate.
AB  - The bioavailability of potassium and magnesium, and the citraturic response were
      determined for the new compound, potassium-magnesium citrate, in 14 normal
      volunteers. Results were compared to those of potassium citrate and magnesium
      citrate. Each subject participated in 4 phases of study: potassium-magnesium
      citrate, potassium citrate, magnesium citrate and potassium chloride. After
      stabilization on a metabolic diet, each subject ingested a single load of a test
      medication followed by timed urine collections for the next 24 hours. Test loads
      included potassium-magnesium citrate (49 mEq. potassium, 24.5 mEq. magnesium and
      73.5 mEq. citrate), potassium citrate (50 mEq.), potassium chloride (50 mEq.) and
      magnesium citrate (25 mEq.) Urinary potassium, magnesium and citrate were
      measured for each collection period. Potassium-magnesium citrate provided an
      equivalent potassium bioavailability as potassium citrate and potassium chloride,
      and a comparable magnesium bioavailability as magnesium citrate. However, it gave
      the highest citraturic response, since the cumulative increment in urinary
      citrate post-load was 129 mg. daily for potassium-magnesium citrate, 105 mg.
      daily for potassium citrate and 35 mg. daily for magnesium citrate. Thus,
      potassium-magnesium citrate gave an optimum citraturic response in addition to
      providing absorbable potassium and magnesium.

PMID- 1988725
TI  - Long-term followup of asymptomatic microhematuria.
AB  - We present a 10 to 20-year followup assessment of 191 patients with unexplained
      microhematuria (including persons with insignificant lesions). Genitourinary
      malignancies did not develop in any of the patients (128 alive and 27 dead)
      evaluated after the first diagnostic investigation. Patient and physician
      compliance with followup protocols was poor. We currently recommend renal
      ultrasound and cystoscopy for the first diagnostic survey, have abandoned routine
      periodic studies and advise diagnostic studies only for patients in whom symptoms
      develop.

PMID- 1988726
TI  - A new single-lumen balloon catheter.
AB  - A new small caliber single-lumen balloon catheter has been devised specifically
      for retrograde ureterography. It is simple to use, does not traumatize the
      intramural ureter and provides excellent ureteral visualization.

PMID- 1988727
TI  - The no-scalpel vasectomy.
AB  - A refined method of delivering the vas deferens for vasectomy has been developed
      and used in China since 1974. This method eliminates the scalpel, results in
      fewer hematomas and infections, and leaves a smaller wound than conventional
      techniques. An extracutaneous fixation ring clamp encircles and firmly secures
      the vas without penetrating the skin. A sharp curved hemostat punctures and
      dilates the scrotal skin and vas sheath. The vas is delivered, cleaned and
      occluded by the surgeon's preferred technique. The contralateral vas is delivered
      through the same opening. The puncture wound contracts to about 2 mm., is not
      visible to the man and requires no sutures for closure. The reported incidence of
      hematoma in 179,741 men followed in China was 0.09%. No hematomas or infections
      were identified in the first 273 procedures performed by a surgeon in the United
      States. The operating time in China and for the last 50 United States procedures
      has ranged from 5 to 11 minutes. The disadvantage of the technique is the hand-on
      training and number of cases necessary to gain proficiency. However, the
      advantages for surgeons and patients should enhance the popularity of vasectomy.

PMID- 1988728
TI  - Endopyelotomy for secondary ureteropelvic junction obstruction in children.
AB  - Percutaneous endopyelotomy has been shown to be successful in treating
      ureteropelvic junction obstruction in adults. Little data have been published
      regarding this procedure in children. We describe 4 patients 6.5 weeks to 5.5
      years old who underwent percutaneous endopyelotomy to treat ureteropelvic
      junction obstruction following failed open dismembered pyeloplasty. Preoperative
      obstruction was demonstrated by a nephrostogram, diuretic renogram and/or
      ultrasonography. Percutaneous endopyelotomy was successful in relieving the
      obstruction in all 4 patients, although 2 required secondary endoscopic
      procedures. One patient had persistent obstruction 40 days after endopyelotomy at
      the ureteropelvic junction and, subsequently, required percutaneous resection of
      a persistent flap of obstructing tissue. In another patient a ureterovesical
      stricture was noted at the time of stent removal, which was treated by endoscopic
      incision. All patients have been followed from 1.5 to 3 years postoperatively.
      Followup diuretic renograms, ultrasound and/or excretory urography demonstrated a
      patent ureteropelvic junction in all patients and all have remained asymptomatic.
      Endopyelotomy appears to be safe and effective in treating secondary
      ureteropelvic junction obstruction in children.

PMID- 1988729
TI  - Continence in bladder exstrophy: determinants of success.
AB  - We evaluated 19 female and 18 male patients with bladder exstrophy, who had
      completed staged reconstruction, had required no further surgery and underwent
      urodynamic studies. Of the male population 61% were continent based on a
      significantly higher urethral continence length (25.8 +/- 6.4 mm., mean plus or
      minus standard error) and a higher urethral closing pressure (69.4 +/- 5.8 cm.
      water) compared to the incontinent male population (11.4 +/- 3.1 mm. and 43.4 +/-
      4.6 cm. water). No significant difference was noted in the bladder capacity of
      these 2 groups. Of the female population 57.9% were continent. They also
      demonstrated a higher urethral continence length (21.1 +/- 4.4 mm.) and a higher
      urethral closing pressure (62.7 +/- 10.2 cm. water) compared to the incontinent
      female subjects (8.4 +/- 2.5 mm. and 32.7 +/- 6.9 cm. water). Moreover, those who
      were continent had a significantly higher bladder capacity (201.2 +/- 39.5 ml.)
      compared to those who were incontinent (84.3 +/- 23.6 ml.). These findings
      support a multifactorial mechanism in achieving continence but they suggest that
      of all the factors urethral length may be the most important.

PMID- 1988730
TI  - Management of posterior urethral strictures secondary to pelvic fractures in
      children.
AB  - Bulboprostatic anastomotic urethroplasty was performed in 20 children with
      posterior urethral strictures secondary to bony pelvic fractures. The approach
      was perineal in 4 children and transpubic abdominoperineal in 16, with good
      postoperative results in 100 and 62.5%, respectively. In some children the
      urethral disruption occurred within the prostate itself and not at the
      prostatomembranous junction. In such cases the proximal sphincteric mechanism may
      be at risk and immediate repair of the injury is advisable. In the case of common
      prostatomembranous disruption displacement of the urethra may be significant. In
      such cases a transpubic approach is preferable. If the proximal sphincteric
      mechanism is deranged, it can be managed at the same time.

PMID- 1988731
TI  - Multifocal, synchronous inverted papillomas involving the ureter.
AB  - Inverted papillomas involving the upper urinary tract remain a rarely diagnosed
      phenomenon. A case of bilateral ureteral inverted papillomas is presented. The
      treatment and diagnosis of this lesion remain a challenge.

PMID- 1988732
TI  - Endometriosis of bladder after menopause.
AB  - We report a rare case of endometriosis of the bladder in a 68-year-old
      postmenopausal woman. The patient had not received any exogenous estrogen therapy
      and the hormone levels were normal for a castrated female subject. Endometriosis
      of the bladder should be considered as a cause of an abnormal mass of the bladder
      even after menopause. This case documents that urinary involvement by
      endometriosis may persist even after years of a hormonally castrated state.

PMID- 1988733
TI  - Pelvic lipomatosis associated with cystitis glandularis and adenocarcinoma of the
      bladder.
AB  - Pelvic lipomatosis is a rare condition characterized by an overgrowth of normal
      fat in the perivesical and perirectal spaces. Cystitis glandularis, cystica or
      follicularis has been observed in 75% of the patients with pelvic lipomatosis.
      Although cystitis glandularis is widely regarded as premalignant few reports have
      documented its transition to adenocarcinoma. We describe a 41-year-old man with
      pelvic lipomatosis in whom primary adenocarcinoma of the bladder developed 6
      years after a histological diagnosis of cystitis cystica and glandularis was
      established. To our knowledge this is the second case reported of pelvic
      lipomatosis associated with proliferative cystitis and adenocarcinoma of the
      bladder, indicating that intestinal metaplasia of the urothelium may be a
      precursor of malignancy in these patients.

PMID- 1988734
TI  - Transrectal ultrasound in the repair of the post-traumatic urethra.

PMID- 1988735
TI  - Polyorchidism: case report and review of literature.
AB  - Polyorchidism is a rare anomaly with approximately 70 cases reported in the
      literature. It may result from transverse division of the urogenital ridge, a
      hypothesis that best explains the anatomical features of the supernumerary
      testicle. The primary accompanying disorders and anomalies include maldescended
      testis, inguinal hernia and torsion. Malignancy has been reported in 3 cases. In
      the absence of any concomitant disorder and if testicular tumor can be ruled out
      by magnetic resonance imaging and ultrasonography, surgical exploration with
      biopsy is unnecessary.

PMID- 1988736
TI  - Locally recurrent endometrioid adenocarcinoma of the prostate after radical
      prostatectomy.
AB  - Endometrioid carcinoma of the prostate is considered a variant of classical
      prostatic ductal carcinoma. Endometrioid carcinoma variant often has the unique
      clinical presentation of gross hematuria. The propensity of this tumor to spread
      within the urothelium makes local failure of curative therapy commonplace. We
      present 2 representative cases with a review of followup surveillance procedures
      and treatment options for the local recurrence once identified.

PMID- 1988737
TI  - This month in Investigative Urology: restoration of erectile function by
      cavernous nerve graft.

PMID- 1988738
TI  - Cavernous nerve grafts restore erectile function in denervated rats.
AB  - Although potency can be preserved in most men following radical prostatectomy, in
      some patients one or both cavernous nerves must be sacrificed in order to excise
      all tumor. For these patients we have considered nerve reconstruction at the time
      of surgery using an interposition nerve graft. This possibility has been tested
      in a rat model. Animals were divided into three groups. In the sham control
      group, a pelvic exploration was conducted without division of the cavernous
      nerves. In the nerve ablation group, a five mm. segment of cavernous nerve was
      excised. In the graft group, five mm. of cavernous nerve was excised bilaterally
      and replaced with an interposition graft of genito-femoral nerve. At one month
      intervals postoperatively animals from each group underwent mating tests to
      determine potency; the ratio of vaginal intromission to unsuccessful mounts (I/M
      ratio) was determined. Following the mating tests the animals were re-explored
      and attempts were made to stimulate erections electrically via the pelvic nerve.
      Results at two months show the I/M ratio of the rats with grafts (0.05) and the
      nerve ablations (0.14) are low compared with the sham operated animals (1.0). By
      month four the graft group (0.89) has approached the sham group (0.91) while the
      ablation group (0.18) remains unchanged (p less than .05). Electrical stimulation
      at month two produced no erections in the nerve ablated or the grafted rats and
      100% erections in the sham-operated animals. At month four, 50% of the rats with
      grafts, 10% of the nerve ablated animals, and 100% of the intact animals produced
      erections upon electrical stimulation (p less than .05). These results suggest
      that cavernous nerve grafting in rats can be successful in restoring potency
      after surgical injury. Application of these techniques to man may be indicated.

PMID- 1988739
TI  - Longitudinal myotomy of ileum for bladder replacement in dogs.
AB  - To evaluate the application of longitudinal myotomy of ileum for bladder
      replacement, pressure/volume characteristics of myotomized ileal segments were
      studied in dogs after incorporation in the urinary tract. In five dogs a 12 cm.
      long myotomized ileal segment was incorporated in the left urinary system as a
      ureteral substitute. These ileal segments did not dilate. In another six animals
      total cystectomy was carried out and the bladder was replaced by a 12 cm. long
      myotomized ileal segment. Urodynamic and radiological studies demonstrated early
      dilatation of these segments, leading to a four-to-five-fold increase in volume
      after six weeks. During filling the intraluminar pressure remained below 20 cm.
      H2O up to two-thirds of the maximal volume and gradually rose when filling was
      continued. High pressure waves were not observed. This study demonstrates that in
      experimental dogs longitudinal myotomy of a short length of ileum results in a
      high volume/low pressure urinary reservoir. This technique is easy to perform,
      requires less bowel compared to current reservoir techniques and leads to
      satisfactory reservoir function.

PMID- 1988740
TI  - Obstruction and recanalization of the ureter during embryonic development.
AB  - Major controversies still exist regarding the terminology, the etiology and the
      pathogenesis of congenital obstructive diseases of the ureter. To try to provide
      some additional information to this controversial subject, a comparative study of
      ureteral development in rat and human embryos, using light and electron
      microscopy, has been performed. During fetal development we observed and
      demonstrated the existence of obstructive phenomena, both at the level of the
      ureterovesical junction (Chwalla's membrane) and along the ureter. At the end of
      the embryonic period, the ureter undergoes a physiologic recanalization process.

PMID- 1988742
TI  - Abstracts, 20th annual meetings: Keystone symposia on molecular and cellular
      biology. The genetic dissection of plant cell processes. January 10-17, 1991.

PMID- 1988741
TI  - Expression of c-erbB-2 gene product in urinary bladder cancer.
AB  - Expression of the c-erbB-2 gene product and the epidermal growth factor receptor
      (EGF-R) was investigated in 54 cases of human bladder cancer immunohistologically
      and by Western blot analysis. For detection of the c-erbB-2 product, two specific
      antibodies, a rabbit polyclonal antibody directed to the intracellular domain and
      a murine monoclonal antibody recognizing an epitope in the extracellular domain,
      were used. Seventeen cases of bladder cancer were stained by the anti-c-erbB-2
      polyclonal antibody, while 20 cases were stained by the monoclonal antibody, with
      good correlation on both stainings (p less than 0.01). There were four c-erbB-2
      positive cases in 26 G1 tumors, four in 15 G2 tumors, and nine in 13 G3 tumors.
      There were also eight erbB-2 positive cases in nine muscle-invasive tumors, nine
      of 45 superficial tumors, four of five with lymph node metastasis, and seven of
      14 without metastasis, as revealed by staining with the polyclonal antibody.
      Thus, the c-erbB-2 gene product was more frequently expressed in high grade
      tumors (p less than 0.01), in high stage tumors (p less than 0.01), and nodal
      metastatic tumors (N.S. by Chi-square test). Twenty-two of the 54 tumors were
      stained by an anti-EGF-R monoclonal antibody, 528 IgG. The expression of EGF-R
      was independent of histological grading, tumor stage, and nodal status, and no
      correlation was observed between expression of the c-erbB-2 product and EGF-R.
      The c-erbB-2 product may be applicable as a tumor marker for evaluation of
      malignant potential, invasiveness, and probably metastatic potential of human
      bladder cancer.

PMID- 1988743
TI  - Abstracts, 20th annual meetings: Keystone symposia on molecular and cellular
      biology. Transgenes, development and disease. January 12-18, 1991.

PMID- 1988744
TI  - Abstracts, 20th annual meetings: Keystone symposia on molecular and cellular
      biology. Self reactivity and its regulation. January 17-24, 1991.

PMID- 1988746
TI  - 20th annual meetings: Keystone symposia on molecular and cellular biology. Gene
      regulation and signalling in endocrine systems. January 19-25, 1991. Abstracts.

PMID- 1988745
TI  - 20th annual meetings: Keystone symposia on molecular and cellular biology. The
      adipose cell: a model for integration of hormone signalling in the regulation of
      cellular function. January 18-24, 1991. Abstracts.

PMID- 1988747
TI  - 20th annual meetings: Keystone symposia on molecular and cellular biology.
      Diabetes and insulin action. January 18-24, 1991. Abstracts.

PMID- 1988748
TI  - 20th annual meetings: Keystone symposia on molecular and cellular biology. Growth
      factor signal transduction. January 19-25, 1991. Abstracts.

PMID- 1988749
TI  - Problems in the diagnosis of the hemoglobinopathies and of polycythemia.

PMID- 1988750
TI  - Treating differentiated thyroid carcinoma: where do we draw the line?

PMID- 1988751
TI  - Follicular thyroid cancer treated at the Mayo Clinic, 1946 through 1970: initial
      manifestations, pathologic findings, therapy, and outcome.
AB  - We retrospectively analyzed the outcome of all patients who received their
      primary treatment for follicular thyroid cancer at the Mayo Clinic between 1946
      and 1970. The diagnosis was confirmed by reexamination of preserved tissue
      specimens. The 57 female and 43 male patients (mean age, 53 years) underwent
      follow-up for a maximum of 32 years (mean, 17.4 years). All patients were treated
      surgically, and total removal of primary tumor was thought to have been
      accomplished in all but three. Only 2 of the 88 patients without distant
      metastatic lesions at the time of initial diagnosis underwent ablation of the
      thyroid remnant. At the conclusion of the study, 52 patients had died, thyroid
      cancer being the cause of death in 19. On the basis of univariate survival
      analysis, age more than 50 years, tumor size that exceeded 3.9 cm, higher tumor
      grade, presence of marked vascular invasion, adjacent tissue invasion, and
      distant metastatic involvement at the time of initial diagnosis were associated
      with increased cancer mortality. Multivariate analysis (by Cox proportional
      hazards model), however, identified only age greater than 50 years, marked
      vascular invasion, and metastatic disease at the time of diagnosis to be
      independent predictors of follicular thyroid cancer-related mortality. Patients
      with two or more of these predictors were classified as being high risk. These
      patients had 5- and 20-year survival rates of 47% and 8%, respectively; the
      corresponding survival data for the low-risk group were 99% at 5 years and 86% at
      20 years. The identification of these risk groups may facilitate a more rational
      approach to treatment of follicular thyroid cancer.

PMID- 1988752
TI  - Rediscovery of crystalline niacin.

PMID- 1988753
TI  - Syphilitic hepatitis.

PMID- 1988754
TI  - Medical folklore: the witch doctor.

PMID- 1988755
TI  - Niacin-induced hepatitis: a potential side effect with low-dose time-release
      niacin.
AB  - Hepatitis developed in five patients who were taking low dosages (3 g/day or
      less) of time-release niacin. In four of the five patients, clinical symptoms of
      hepatitis developed after the medication had been taken for a relatively short
      time (2 days to 7 weeks). This manifestation of hepatotoxicity seems to differ
      from that previously reported in association with use of crystalline niacin,
      which occurred with high dosage and prolonged usage of the medication. In view of
      the recent increased frequency of prescribing niacin for the treatment of
      hyperlipidemia, physicians should be aware of the potential for hepatotoxicity
      with even low-dose and short-term use of time-release niacin.

PMID- 1988757
TI  - Public health and the Doctors Mayo.

PMID- 1988756
TI  - Roentgenologic features of pulmonary blastomycosis.
AB  - In 35 cases of pulmonary blastomycosis, the roentgenologic features were as
      follows: consolidation 26%, mass 31%, intermediate-sized nodules 6%, miliary
      pattern 11%, solitary cavity 9%, fibrotic and cavitary changes 6%, interstitial
      pattern 6%, diffuse alveolar involvement 3%, and mixed alveolar and interstitial
      infiltrate 3%. All symptomatic cases of consolidation were acute (symptoms for
      less than 1 month), and most were in young patients (mean age, 34 years).
      Consolidation constituted 58% of the acute cases in this series. Two of the nine
      cases of consolidation were asymptomatic epidemic cases detected by screening. A
      pulmonary mass was the most common initial manifestation in this series; it
      tended to occur in patients with chronic symptoms (more than 1 month). The mass
      was considered suggestive enough of bronchogenic carcinoma to necessitate
      resection in 55% of cases. The military form of pulmonary blastomycosis occurred
      in older patients with disseminated disease. Fibrotic and cavitary disease was
      chronic in nature. The presence of intermediate-sized nodules elsewhere in the
      lung proved to be a helpful diagnostic finding in several patients with
      consolidation, mass, or cavitary disease. Hilar adenopathy, postinfectious
      calcification, chest wall invasion, and pleural effusion occurred infrequently or
      not at all in this series.

PMID- 1988758
TI  - Coronary artery bypass operation in dialysis patients.
AB  - To analyze the short- and long-term morbidity and mortality among maintenance
      dialysis patients who have undergone coronary artery bypass operations, we
      identified 25 such patients at the Mayo Clinic and three recently published large
      single-center studies that provided sufficient detail for meaningful comparison.
      Two independent observers reviewed the new information with regard to pertinent
      historical, clinical, and laboratory data. The perioperative mortality was 20%.
      Among the perioperative survivors, 1- and 2-year survival rates were 95% and 77%,
      respectively. The 3-year actuarial survival was 70%. Uniformly, the symptoms
      diminished, and the need for antianginal medication was decreased. In the three
      other large published series, the perioperative mortality ranged from 3 to 20%,
      and coronary artery bypass performed earlier after the onset of the symptoms
      seemed to result in a lower perioperative mortality. We conclude that elective
      coronary artery bypass in dialysis patients is associated with acceptable short
      term morbidity and mortality and effective relief of symptoms. Surgically treated
      patients may have a survival advantage. Thus, we advocate aggressive early
      investigation and surgical treatment of these patients.

PMID- 1988759
TI  - Hemoglobin Columbia Missouri or alpha 2[88 (F9) Ala----Val]beta 2: a new high
      oxygen-affinity hemoglobin that causes erythrocytosis.
AB  - A previously undescribed hemoglobin variant, hemoglobin Columbia Missouri, alpha
      88 (F9) Ala----Val, was detected in a 22-year-old white man who was undergoing
      assessment for erythrocytosis. This new hemoglobin variant does not separate from
      hemoglobin A by electrophoresis in conventional media, by isoelectric focusing,
      or by electrophoresis of purified globin chains in 8 M urea. It exhibits a high
      oxygen affinity, with a P50 (oxygen tension at 50% saturation) of 19.3 torr for
      the patient's whole blood. The substitution of hemoglobin Columbia Missouri is an
      internal residue near the end of the F helix of the alpha chain. Hemoglobin
      Okazaki has an arginyl residue substitution for a cysteinyl residue at F9 (beta
      93) in the beta chain. In comparison with hemoglobin Okazaki, the substitution in
      hemoglobin Columbia Missouri has a more pronounced effect on oxygen affinity.
      Consequently, hemoglobin Columbia Missouri is associated with erythrocytosis,
      whereas hemoglobin Okazaki is not.

PMID- 1988760
TI  - Motor neuron disease (amyotrophic lateral sclerosis).
AB  - Amyotrophic lateral sclerosis is an insidiously developing, adult-onset,
      progressive anterior horn cell degeneration with associated degeneration of
      descending motor pathways. It has been recognized as an important clinical
      syndrome since the middle of the 19th century. Despite increasing clinical and
      research interest in this condition, its cause remains obscure, even in the
      broadest terms. Epidemiologic characteristics of the disease have been
      interpreted as evidence of both genetic and environmental causes. A major change
      in the view of this disease is the widely developing perception that it is a
      disease of elderly persons more than of middle-aged adults as was previously
      taught. Etiologic hypotheses encompass a broad range of postulated
      pathophysiologic mechanisms, and we review these in detail. The clinical limits
      of the disease can now be better defined by using modern diagnostic techniques.
      Although interest in supportive symptomatic therapy is growing, no intervention
      has yet been shown to modify the biologically determined motor system
      degeneration.

PMID- 1988761
TI  - Common variable immunodeficiency: the disorder and treatment.
AB  - A case of common variable immunodeficiency, a relatively rare disorder, is
      presented. This case was complicated by the presence of an anti-IgA antibody in
      the patient's serum and a history of a possible anaphylactic reaction to a prior
      intravenous infusion of gamma-globulin. Common variable immunodeficiency is
      actually a heterogeneous group of demonstrable immunoglobulin deficiencies that
      have in common low levels of most immunoglobulin isotypes, the inability to form
      antibodies to antigen, an absence of gross defects in cell-mediated immunity, and
      the presence of recurrent bacterial infections. The history of immunoglobulin
      deficiency and its treatment is reviewed. Although the primary therapy for common
      variable immunodeficiency is gamma-globulin replacement, ancillary measures such
      as early treatment of infections with antibiotics are also important. Intravenous
      gamma-globulin replacement therapy is preferred to intramuscular replacement
      therapy in these patients because intramuscular doses must be limited in volume
      to minimize local pain and take 2 to 14 days to achieve maximal blood levels,
      during which time in situ degradation of up to 50% of the administered dose can
      occur. Five intravenous gamma-globulin preparations are currently available in
      the United States. The potential adverse effects of intravenous gamma-globulin
      infusion and the precautions currently taken to ensure safety during
      administration of this product are discussed.

PMID- 1988762
TI  - Layoffs and reassignments: psychological self-defense.

PMID- 1988763
TI  - Fungal tracheobronchitis. Report of 9 cases and review of the literature.
AB  - Clinical, roentgenographic and pathologic findings are described in 9 patients
      with fungal tracheobronchitis and comparison is made with 25 additional cases in
      the literature. Two morphologic patterns were identified: the first appears as a
      pseudomembrane of necrotic tissue, exudate, and fungal hyphae involving more-or
      less the entire circumference of the bronchial wall or as mucus/fungus plugs
      completely occluding the airway lumen; the second consists of single or multiple
      discrete plaques on the airway wall, sometimes associated with invasion of the
      adjacent lung parenchyma or pulmonary artery. As with more invasive forms of
      fungal infection, a compromise in host defenses is probably the most important
      factor leading to fungal colonization and subsequent local invasion. Malignancies
      of the hematologic and lymphoreticular systems, solid neoplasms,
      granulocytopenia, and a history of a protracted course of broad-spectrum
      antibiotics, corticosteroids, and chemotherapy were present in most of our
      patients and in those reported in the literature. Despite this, there is some
      evidence that tracheobronchitis may occur in individuals with a relatively lesser
      degree of host defense impairment. Local damage to the airway wall such as occurs
      with prolonged mechanical ventilatory support, neoplastic infiltration, or
      nonfungal infection may also be a factor predisposing to fungal colonization and
      invasion. In 4 of our patients, the fungal infection of the tracheobronchial tree
      probably contributed significantly to the development of terminal respiratory
      failure. Although recognition of the infection may not have altered the course of
      the underlying disease in some of our patients, in others identification and
      early treatment might have been life-saving. Thus, culture and histologic
      examination of bronchoscopically identified tracheobronchial mucus plugs and
      necrotic material should be performed in all immunocompromised individuals.

PMID- 1988764
TI  - Tourette syndrome and other tic disorders. Diagnosis, pathophysiology, and
      treatment.
AB  - In this report, we discuss the definition, characteristics, pathophysiology, and
      treatment of tic disorders with a major emphasis on Tourette syndrome. Although
      the diagnosis of a tic disorder depends on the presence of motor and/or phonic
      tic(s), patients with these problems also have a variety of co-morbid features
      including obsessive-compulsive symptoms, attention-deficit hyperactivity
      disorder, behavioral difficulties, and learning disabilities. Conservative
      estimates for Tourette syndrome suggest a prevalence rate of 0.1-1.0 per 1000.
      This syndrome is inherited in a sex-influenced autosomal dominant pattern with
      either chronic multiple tic disorder or obsessive-compulsive disorder as
      alternative phenotypes of the putative gene. Current evidence continues to
      support a pathophysiologic mechanism involving synaptic neurotransmission, with
      the dopaminergic system as a primary candidate. Therapeutically, it is essential
      to clarify whether a patient's problems are related to tics or associated
      behavioral difficulties. Pharmacotherapy for motor and phonic tics is strictly
      symptomatic and should be reserved for those with functionally disabling
      symptoms. A comprehensive individualized treatment program is often required in
      the care of individuals with tic disorders.

PMID- 1988765
TI  - Chromogranin A storage and secretion: sensitivity and specificity for the
      diagnosis of pheochromocytoma.
AB  - Chromogranin A, co-stored and co-released with catecholamines from adrenal
      medullary and sympathetic neuronal vesicles, is elevated in the plasma of
      patients with pheochromocytoma. The usefulness of the hormone in the differential
      diagnosis of hypertension is examined. An elevated level of chromogranin A had
      comparable diagnostic sensitivity (83%, 24/29) to, but greater diagnostic
      specificity (96%, 86/90) than the level of plasma catecholamines when subjects
      with pheochromocytoma (n = 29) were evaluated in comparison to several reference
      groups, including normotensive controls (n = 49), subjects with essential
      hypertension (n = 28), subjects with renovascular hypertension (n = 5), and
      subjects with primary aldosteronism (n = 3). Subjects with signs or symptoms
      suggesting pheochromocytoma, but in whom the diagnosis was ultimately ruled out
      (n = 5) had normal plasma levels of chromogranin A. A modest rise in chromogranin
      A in those with essential hypertension, and correlation of chromogranin A with
      diastolic blood pressure in normotensive patients and patients with essential
      hypertension did not impair the diagnostic usefulness of chromogranin A for
      pheochromocytoma. Renal failure was associated with an elevated plasma
      chromogranin A independently of blood pressure. Plasma chromogranin A correlated
      with tumor mass, tumor chromogranin A content, tumor norepinephrine content, and
      urinary vanillylmandelic acid excretion; it did not correlate with plasma or
      urinary catecholamines, nor with blood pressure in patients with
      pheochromocytoma. Plasma chromogranin A levels did not differ in subjects with
      pheochromocytoma when stratified by age, sex, tumor location, or tumor pathology.
      Several drugs used in the diagnosis or treatment of pheochromocytoma (clonidine,
      metoprolol, phentolamine, and tyramine) had little effect on plasma chromogranin
      A concentration. Within the pheochromocytoma, chromogranin A was localized along
      with catecholamines to the soluble core of chromaffin granules, where it
      accounted for 18 +/- 5% of vesicle soluble protein. We conclude that 1)
      chromogranin A emerges along with catecholamines from pheochromocytoma chromaffin
      granules; 2) plasma chromogranin A is a sensitive and specific diagnostic tool in
      evaluation of actual or suspected pheochromocytoma; 3) plasma chromogranin A
      predicts pheochromocytoma tumor size and overall catecholamine production; and 4)
      drugs commonly employed in the diagnosis or treatment of pheochromocytoma have
      little effect on plasma chromogranin A level, preserving the usefulness of
      chromogranin A in evaluating pheochromocytoma. Thus, measurement of chromogranin
      A provides a useful adjunct to the diagnosis of pheochromocytoma.

PMID- 1988766
TI  - A simplified diagnostic approach to pheochromocytoma. A review of the literature
      and report of one institution's experience.
AB  - Pheochromocytoma is an unusual but potentially devastating tumor. Although a high
      index of suspicion is necessary, the likelihood of a pheochromocytoma is lower in
      the absence of the typical symptoms and findings. Nonetheless, screening must be
      broadened to include patients with a lower risk of the disease, such as those
      with resistant or labile hypertension who are minimally symptomatic. Extensive
      diagnostic evaluations should be reserved for those whose clinical or laboratory
      findings are more suggestive. Symptoms in a group of patients in whom a
      pheochromocytoma was seriously considered but excluded overlap symptoms in
      patients with a pheochromocytoma. Certain symptoms are useful: flushing to
      suggest a non-pheochromocytoma illness; visual symptoms, flank pain, and pallor
      to suggest that a pheochromocytoma is more likely. Combinations of symptoms can
      be of value: 2 or more symptoms from the triad of headache, palpitations, and
      diaphoresis were present in the majority of pheochromocytoma patients, but in a
      smaller number of non-pheochromocytoma patients. The presence of the entire triad
      is more specific, but less sensitive. New hypertension, or hypertension
      associated with unexplained orthostatic hypotension, are suggestive of an
      underlying pheochromocytoma. Twenty-four-hour urine studies are consistently
      abnormal in patients with a pheochromocytoma, but are also elevated in a
      significant proportion of non-pheochromocytoma patients. Values greater then 1.5
      2-fold above the upper limit of normal are very suggestive that a
      pheochromocytoma is present, and warrant a more intensive subsequent evaluation.
      Imaging studies are reliable in the diagnosis of pheochromocytoma, and can help
      to confirm or exclude the disease. Patients with a higher clinical likelihood and
      any elevated urinary testing, or with a lower clinical likelihood and
      persistently and/or significantly elevated urinary testing, should have imaging
      studies performed. This combination of clinical screening, 24-hour urinary
      testing, and imaging studies is a useful and reliable approach to patients
      suspected of harboring a pheochromocytoma.

PMID- 1988767
TI  - Tinsley Randolph Harrison 1900-1978. "The pathogenesis of congestive heart
      failure": then and now. 1935.

PMID- 1988768
TI  - Effects of monosodium glutamate and gold thioglucose on dietary regulation of
      sympathetic nervous system activity in rodents.
AB  - Neonatal administration of monosodium glutamate (MSG) disrupts hypothalamic
      regulation of a number of neuroendocrine systems. Studies described in this
      report using techniques of norepinephrine (NE) turnover examined sympathetic
      nervous system (SNS) activity in heart and interscapular brown adipose tissue
      (IBAT) of animals given MSG as neonates. Although in every experiment overall
      rates of NE turnover were lower in MSG-treated mice and rats, the differences
      were due exclusively to diminished tissue NE content, especially in IBAT.
      Fractional rates of NE turnover did not differ between groups. In contrast to
      animals with lesions in the ventromedial hypothalamus produced by gold
      thioglucose (AuTG) or electric current, MSG-treated mice and rats varied SNS
      activity in heart and IBAT in accord with changes in nutrient intake. Thus, SNS
      activity, both at baseline and in response to dietary manipulation, is probably
      not affected by neonatal MSG administration.

PMID- 1988769
TI  - Influence of portal delivery of insulin on intracellular glucose and lipid
      metabolism.
AB  - We have investigated whether portal delivery of insulin as a result of
      intrahepatic islet cell autografts would prevent the development of metabolic
      alterations. Seven pancreatectomized dogs received islet autografts transplanted
      into the liver through the portal vein (PD). One year after transplantation,
      their intravenous glucose tolerance and insulin responses were similar to age
      matched control (C) dogs (n = 5). Also, normal triglyceride content in arterial
      smooth muscle and striated muscle was observed in the dogs with portal insulin
      delivery in contrast to the substantial increases we observed in
      pancreatectomized dogs (n = 7) with pancreatic autografts that drained into the
      systemic circulation (SD). In these dogs, the tissue samples were taken at the
      age of 3 to 4 years. Triglyceride content (mean +/- SEM) in the aorta was 4.9 +/-
      1.2 versus 2.6 +/- 0.6 versus 20.7 +/- 8.0 mumol/g (P less than .01) in C, PD,
      and SD models, respectively. The corresponding values for triglyceride content in
      striated muscles were 29.1 +/- 1.2, 25.9 +/- 1.5, and 171.4 +/- 46.6 mumol/g (P
      less than .01). Glucose-6-phosphate dehydrogenase (G-6-PDH) and malic enzyme, key
      enzymes for lipid synthesis, were also normal in the PD model, in contrast to the
      fivefold increased activity of these enzymes in the SD model (P less than .01).
      The glycolytic enzymes, hexokinase (HK) and phosphofructokinase (PFK), were
      normal compared with the decreased values in the SD. These data indicate that it
      is possible to normalize glucose and lipid metabolism in arterial walls by portal
      delivery of insulin, following intrahepatic islet cell transplantation.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1988770
TI  - Characterization of high-density lipoprotein binding to guinea pig hepatic
      membranes: effects of dietary fat quality and cholesterol feeding.
AB  - The effects of dietary fat quality and cholesterol intake on expression of guinea
      pig hepatic membrane high-density lipoprotein (HDL) binding sites were studied.
      Animals were fed semisynthetic diets containing 7.5% (wt/wt) of either corn oil
      (CO), olive oil (OL), or lard. The cholesterol diet was prepared by incorporating
      0.25% recrystallized cholesterol into standard guinea pig chow. Plasma
      cholesterol levels of guinea pigs on the CO diet were significantly lower (P less
      than .02) than animals on the OL or lard diets. HDL cholesterol levels did not
      differ between the polyunsaturated, monounsaturated, and saturated dietary fat
      groups. Guinea pigs on the high cholesterol diet had increased total and HDL
      cholesterol levels compared with animals on the chow diet (P less than .01).
      Initial studies demonstrated that HDL binding to hepatic membranes was
      temperature-dependent. A threefold increase in binding was observed when assays
      were performed at 37 degrees C, as compared with 4 degrees C, for all membrane
      preparations. Dietary fat quality and dietary cholesterol intake significantly
      altered HDL binding to hepatic membranes with increased HDL binding to membranes
      of animals fed polyunsaturated fat and the high cholesterol diet. At 37 degrees
      C, HDL binding to hepatic membranes of CO-fed animals was 26% and 46% higher than
      for membranes of OL- and lard-fed guinea pigs, respectively. A high cholesterol
      intake increased HDL binding by 24% at both 4 degrees C and 37 degrees C.
      Scatchard analysis demonstrated that while membrane affinity for HDL (Kd) was not
      affected by diet, changes did occur in the total number of HDL binding
      sites.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1988771
TI  - Urinary desmosine, elastolysis, and lung disease.
AB  - Desmosine is an amino acid specific to elastin. Animal studies suggest that
      urinary desmosine (UD) represents endogenous elastin degradation. Therefore, UD
      has previously been used to investigate endogenous elastolysis, but was not
      elevated in subjects with chronic obstructive airways disease (COAD), although
      accelerated pulmonary elastolysis is thought to contribute to COAD. We have
      investigated whether this reflects large day-to-day and between-subject variation
      in UD and whether, in man, dietary desmosine contributes significantly to that in
      urine. Mean 24-hour UD output (over 5 consecutive days) from 10 asymptomatic
      subjects (5 males) was higher in males than females (77.4 +/- 9.6 and 40.2 +/-
      5.0 nmol/24 hours, respectively; mean +/- SD, P less than .001), but not
      significantly different when expressed in terms of creatinine (micrograms
      desmosine/100 mg creatinine: males, 2.5 +/- 0.4; females, 3.1 +/- 0.8; mean +/-
      SD). The lowest between-subject variation was observed when the mean of 5 days'
      24-hour UD values was analyzed on the basis of gender (coefficient of variation
      [CV], 12.5%); when gender was not considered, the least between-subject variation
      was found for the mean of 5 days' desmosine/creatinine analysis (CV, 24.5%).
      Approximately 1% of dietary desmosine (ingested as [3H]elastin and [3H]
      desmosine) was excreted in the urine within 24 hours, contributing approximately
      15% of UD while on a normal diet. Although ingestion of a low elastin diet (less
      than 1/10 desmosine/24 hours than a normal diet) resulted in lower within-subject
      variation in 24-hour UD excretion (mean CV decreased from 31.5% to 20.2%), the
      between-subject CV and UD levels did not alter.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1988772
TI  - Reduced mononuclear leukocyte ascorbic acid content in adults with insulin
      dependent diabetes mellitus consuming adequate dietary vitamin C.
AB  - Several recent studies suggest that vitamin C (ascorbic acid [AA]) status may be
      altered in insulin-dependent diabetes mellitus (IDDM). We measured the AA content
      of mononuclear leukocytes (MN-AA) as an indicator of tissue vitamin C status in
      adults with IDDM and nondiabetic adults matched for age and sex. Dietary vitamin
      C intake and plasma AA were analyzed to ensure that vitamin C availability was
      adequate. Dietary vitamin C intakes were above recommendations and were not
      different between the groups. MN-AA was reduced by 33% on average (P less than
      .05) in adults with IDDM (1.75 microgram/mg total protein [TP]) when compared
      with nondiabetics (2.60 micrograms/mg TP). When MN-AA is indexed to the dietary
      vitamin C intake (MN-AA/100 mg diet C), the storage deficit in adults with IDDM
      averages 50% (P less than .05). This observation suggests an impaired tissue AA
      storage in adults with IDDM and supports the theory that intracellular scurvy
      contributes to the chronic degenerative complications of the disease.

PMID- 1988773
TI  - Effect of glucose and insulin on immunoreactive endothelin-1 release from
      cultured porcine aortic endothelial cells.
AB  - We measured the release of immunoreactive endothelin-1 (IR-ET-1) by cultured
      porcine aortic endothelial cells under normoglycemic (5.5 mmol/L) and
      hyperglycemic (27.5 and 55 mmol/L) conditions. Compared with cells incubated in
      the presence of a normal glucose concentration, cells incubated in 27.5 mmol/L
      glucose medium released 52% less IR-ET-1, and those incubated in 55 mmol/L
      glucose medium released 54% less IR-ET-1. The observed effects of elevated
      glucose on IR-ET-1 release were both sugar-specific and not due to increased
      osmolarity. Fetal calf serum (FCS)-stimulated IR-ET-1 release in the presence of
      elevated glucose was also less than that in the presence of a normal glucose
      concentration. In addition, the effects of two hormones, insulin and insulin-like
      growth factor 1 (IGF-1), on IR-ET-1 release were examined. Both insulin and IGF-1
      dose-dependently stimulated IR-ET-1 release. Twenty micrograms/mL insulin and 10(
      8) mol/L IGF-1 increased IR-ET-1 release by 38% and by 44%, respectively. These
      results indicate that hyperglycemic condition results in reduction of IR-ET-1
      release from cultured porcine aortic endothelial cells and that insulin and IGF-1
      stimulate its release. The possible relevance of these observations to
      physiological regulation of ET-1 release in vivo and pathological processes in
      diabetes remains to be established.

PMID- 1988774
TI  - Cimetidine inhibits catechol estrogen metabolism in women.
AB  - Chronic cimetidine use in men is associated with hyperestrogenic side effects
      such as gynecomastia, which may be linked to inhibition of estradiol 2
      hydroxylation. As this property of the drug might be helpful in hypoestrogenic
      states such as osteoporosis, we investigated the effect of cimetidine on
      estradiol metabolism in premenopausal and postmenopausal women. Using an in vivo
      radiometric assay, we found that the extent of estradiol 2-hydroxylation in
      premenopausal women (n = 9) was decreased by a 1-month course of cimetidine, 800
      mg twice daily (44.0% +/- 3.5% v 31.2% +/- 4.1%, P less than .001). Among
      premenopausal smokers (n = 3), the response to cimetidine was approximately the
      same as nonsmokers. Serum estradiol levels (follicular phase) in these women were
      unaltered by cimetidine after 1 month, while concentrations of sex hormone
      binding globulin (SHBG) were decreased by 30% (P = .018). Postmenopausal women (n
      = 5) initially received a lower dose of cimetidine (600 mg twice daily) for 2
      weeks, followed by a higher dose (1200 mg twice daily) for another 2 weeks. The
      extent of estradiol 2-hydroxylation was significantly reduced by the low dose
      (44.4% +/- 4.5% v 24.3% +/- 3.0%, P less than .005), with minimal further
      reduction after the high dose (21.7% +/- 1.6%). After 4 weeks of cimetidine
      treatment, serum estradiol levels increased significantly from 30.0 +/- 6.4 to
      59.8 +/- 13.1 pg/mL (P = .033), while SHBG was unaffected. Cimetidine was found
      to have little effect on selected biochemical indices of bone and calcium
      metabolism in both groups of women.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1988775
TI  - Fatty acid composition of serum lipids and erythrocyte membranes in type 2 (non
      insulin-dependent) diabetic men.
AB  - The fatty acid (FA) composition of serum lipids and erythrocytes was studied in
      21 men with non-insulin-dependent diabetes mellitus (NIDDM) and in 14 normal
      subjects matched for age, sex, body weight, and dietary intake. Lower levels of
      linoleic acid and higher levels of highly unsaturated FA (daughter) of n-3 and n
      6 family FA, reflected in a higher unsaturation index, were found in serum
      phospholipids (S-PL), in phospholipids of erythrocyte membranes (ery-PL), and in
      serum cholesterolesters (S-CHE). The unsaturation index of serum phospholipids
      significantly correlated with glycosylated hemoglobin A1c (P less than .05) and
      blood glucose levels after glucose load (P less than .001). The results suggest
      that elongation and desaturation of essential FA (linoleic acid in particular)
      are increased. The above changes may be associated with accelerated
      atherosclerosis in type 2 diabetics.

PMID- 1988777
TI  - Sodium retention by insulin may depend on decreased plasma potassium.
AB  - Evidence is accumulating that insulin is a hypertensive factor in humans. The
      involved mechanism may be its sodium-retaining effect. We examined whether
      insulin causes sodium retention through a direct action on the kidney, as is
      generally assumed, or indirectly through hypokalemia. Insulin was infused
      (euglycemic clamp technique) with and without potassium infusion to prevent
      hypokalemia in six healthy subjects. Without potassium infusion, insulin caused a
      marked decrease in plasma potassium (-0.75 mmol/L), and decreased urinary sodium
      and potassium excretions by, approximately 38% and 65%, respectively.
      Simultaneous potassium infusion largely prevented the decrease in plasma
      potassium, as well as the decrease in urinary sodium and potassium excretions.
      These data suggest that the acute antinatriuretic effect of insulin may be
      largely mediated in an indirect way, ie, through hypokalemia.

PMID- 1988776
TI  - Nocturnal growth hormone secretion does not affect diurnal variations in arginine
      and glucose-stimulated insulin secretion.
AB  - There is a diurnal variation in insulin secretion, with higher values in the
      morning (AM) than in the afternoon (PM). This study tested the hypothesis that
      nocturnal human growth hormone (hGH) secretion might be the mechanism producing
      this diurnal variation in insulin secretion. Six healthy normal-weight men were
      studied on four occasions: twice in the early morning (AM) and twice in the
      afternoon (PM). Oral methscopolamine (Pamine), an anticholinergic agent that
      blocks hGH release, was administered at bedtime prior to the AM study or before
      breakfast for the PM study. An index of insulin secretion in all four tests was
      obtained from measurement of the acute release of insulin in response to two
      intravenous (IV) boluses of arginine, one given basally and the other given after
      raising glucose levels to approximately 150 mg/dL above the baseline. Insulin
      secretion was significantly greater in the morning than in the afternoon in both
      control and methscopolamine-pretreated subjects. The mean peak hGH was reduced in
      subjects pretreated with oral methscopolamine. Drug treatment reduced insulin
      secretion proportionally in the morning and afternoon. These results suggest that
      the diurnal insulin response to stimulation with arginine during a hyperglycemic
      clamp persists despite complete suppression of hGH by anticholinergic blockade,
      and that the diurnal insulin secretion is not caused by sleep- or meal-induced GH
      secretion.

PMID- 1988779
TI  - Rickets in Nigerian children: a consequence of calcium malnutrition.
AB  - Eleven Nigerian children with clinically and radiologically proven rickets were
      assessed biochemically. The children had low or low normal concentrations of
      total and corrected calcium, and elevated plasma alkaline phosphatase (ALP)
      activity, but normal plasma phosphate concentrations. Their serum 25
      hydroxyvitamin D (25-OHD) and 1,25-dihydroxyvitamin D (1,25-(OH)2D)
      concentrations were not significantly different from those in controls, but the
      ratio of 1,25-(OH)2D to 25-OHD was significantly greater than that in controls.
      Parathyroid hormone (PTH) concentrations were greater in rachitic children, and
      there was a significant correlation between 1,25-(OH)2D and PTH concentrations.
      Osteocalcin concentrations in rachitic children were not significantly different
      from those in controls, but they were markedly elevated in the three patients
      with the highest 1,25-(OH)2D and PTH concentrations. One child, from whom a
      sample of bone (from a corrective osteotomy) was available for histological
      examination, showed markedly thickened osteoid seams, characteristic of rickets.
      All the rachitic children had a calcium intake of less than 150 mg daily.
      Treatment of these rachitic children with calcium gluconate (1 g/d) led to
      clinical, radiological, and biochemical healing of rickets. We conclude that
      rickets in Nigerian children is not due to vitamin D deficiency, but to a lack of
      calcium. This observation has implications regarding the pathogenesis, treatment,
      and prevention of rickets/osteomalacia in Nigeria and possibly other African and
      tropical countries.

PMID- 1988778
TI  - The carboxy-terminal propeptide of type I procollagen in serum as a marker of
      bone formation: the effect of nandrolone decanoate and female sex hormones.
AB  - Seventy-nine osteoporotic (prior forearm or vertebral fracture), but otherwise
      healthy, postmenopausal women (aged 55 to 75 years) were allocated to two double
      blind trials: (1) 39 women received either nandrolone decanoate (anabolic
      steroid) 50 mg as an intramuscular depot injection or a placebo injection every 3
      weeks for 1 year; and (2) 40 women received either 2 mg 17 beta-estradiol plus 1
      mg norethisterone acetate or placebo tablets daily for 1 year. Sixty-seven (85%)
      completed the 1 year of treatment. Serum concentration of type I procollagen
      carboxy-terminal propeptide (PICP) was measured before and at 3, 6, 9, and 12
      months of therapy. In addition, 32 of the women had an iliac bone biopsy taken
      after double tetracycline labeling. Initial serum PICP correlated significantly
      with histomorphometrically measured rate of bone formation (r = .4; P less than
      .05) and plasma bone Gla protein (r = .6; P less than .001), but not with
      histomorphometrically measured bone resorption or biochemical estimates of bone
      resorption (fasting urinary hydroxyproline and calcium). Estrogen-progestogen
      therapy significantly decreased (P less than .001) serum PICP by about 30%,
      whereas anabolic steroid therapy hardly affected it. We conclude that serum PICP
      may be used as a noninvasive measurement of bone formation on a group basis.
      Whereas bone formation is clearly decreased during estrogen-progestogen therapy,
      it is not affected by long-term therapy with anabolic steroids.

PMID- 1988780
TI  - Tissue-specific regulation of lipoprotein lipase activity by insulin/glucose in
      normal-weight humans.
AB  - Eight normal-weight subjects (four men, four women) were studied to determine the
      relative activities of lipoprotein lipase (LPL) in adipose tissue (ATLPL) and
      vastus lateralis skeletal muscle (SMLPL), both in the fasting state and in
      response to a 6-hour insulin/glucose infusion. Mean fasting levels of ATLPL and
      SMLPL were not statistically different. After 6 hours of insulin/glucose
      infusion, mean ATLPL activity was significantly greater than the fasting level (P
      less than .01), while mean SMLPL activity decreased from basal (P less than .05).
      These tissue-specific changes in LPL responsiveness (0 to 6 hours) were
      significantly different (P less than .01). No differences between men and women
      were observed. These divergent tissue-specific LPL responses to insulin/glucose
      would serve to direct lipoprotein triglyceride-derived fatty acids away from
      muscle and to adipose tissue for storage.

PMID- 1988782
TI  - Helmets for bicyclists--another first for Victoria.

PMID- 1988781
TI  - Apolipoprotein E polymorphism influences the serum cholesterol response to
      dietary intervention.
AB  - The association between apolipoprotein (apo) E polymorphism and the response of
      serum cholesterol to dietary counseling and to gemfibrozil treatment was
      investigated in 230 dyslipidemic middle-aged participants of the Helsinki Heart
      Study. Baseline lipid levels were not significantly different between subjects
      with or without the epsilon 4 allele. Following dietary counseling, participants
      with the epsilon 4 allele exhibited a greater reduction in serum total
      cholesterol (P less than .01) and low-density lipoprotein (LDL)-cholesterol (P
      less than .02) than those without the epsilon 4 allele, while the changes in high
      density lipoprotein (HDL)-cholesterol and triglycerides were similar in the two
      groups. The alterations observed in total cholesterol, HDL-cholesterol, and
      triglycerides during treatment with gemfibrozil were not different between
      subjects with or without the epsilon 4 allele. The presence of the epsilon 4
      allele and baseline serum cholesterol independently predicted the degree of
      cholesterol reduction following dietary counseling.

PMID- 1988783
TI  - Privacy laws and their effect on medical research.

PMID- 1988784
TI  - ACE inhibitors in myocardial ischaemia.

PMID- 1988785
TI  - Kaposi's sarcoma: what's in control?

PMID- 1988786
TI  - Child drownings: a changing pattern.
AB  - Paediatric drownings in New South Wales during the years 1987-1990 are reviewed
      to document the current pattern. Over these three years we have registered 250
      paediatric deaths by physical injury. Sixty-one (24%) of these deaths were by
      drowning. Twenty-nine of the 61 drownings (47%) occurred in domestic pools; 25 of
      these were in unfenced or inadequately fenced pools. Of the remaining four cases,
      one was associated with a chair being used to gain access and the other three
      remain unexplained. Thirty-three of the 61 drownings occurred in country areas;
      of these 10 were in pools, eight in rivers or creeks, six in boating accidents,
      four in the surf and three in dams. A changing trend identified by this study is
      the increasing percentage of drownings (44%) occurring in nominally "fenced"
      pools in which the fencing was not functioning because the gate was open or the
      fencing was in disrepair. Legislation must be supported by public education and
      council inspection if the full benefit of isolation fencing is to be realised.
      With respect to all drownings there is a continuing need for education about the
      dangers that bodies of water, even in the bath or a bucket, pose to young
      children, and the need for parents to strive for optimal supervision.

PMID- 1988787
TI  - Lipid and apolipoprotein levels in an Australian community.
AB  - Serum levels of total and high density lipoprotein (HDL) cholesterol and
      apolipoproteins A1 and B were measured in over 600 men and women aged 30-69 years
      who were selected at random from an Australian community. Total cholesterol and
      apolipoprotein A1 and B levels increased with age, with this effect being most
      pronounced for total cholesterol and apolipoprotein B in women. Body mass index
      and waist-to-hip ratio were positively correlated with apolipoprotein B and total
      cholesterol levels, and negatively correlated with apolipoprotein A1 and HDL
      cholesterol levels. All lipid and apolipoprotein A1 levels increased with the
      quantity of alcohol consumed. After adjusting for age, body mass index and
      smoking, the association with alcohol was strongest for apolipoprotein A1 and HDL
      cholesterol levels in men (P = 0.0001), and for apolipoprotein A1 levels in women
      (P = 0.01). Levels of apolipoprotein A1 and HDL cholesterol were lower, and of
      apolipoprotein B and total cholesterol were higher, in current cigarette smokers
      than non-smokers, with significant associations for apolipoprotein B (P = 0.004)
      and HDL cholesterol levels (P = 0.04) in men. In general, the associations
      between apolipoprotein A1 levels and the other variables were weaker than those
      for HDL cholesterol levels, whereas the associations with apolipoprotein B levels
      were stronger than those for total cholesterol levels (except for alcohol
      consumption). Thus, obesity, alcohol consumption and cigarette smoking should be
      considered when interpreting apolipoprotein levels.

PMID- 1988788
TI  - Gastrointestinal bleeding with influenza virus.
AB  - Seven children who presented during the influenza A(H1N1) epidemic of 1988 are
      described. After a typical influenzal illness, they developed haematemesis of
      varying severity. Endoscopy revealed haemorrhagic gastritis. Laboratory evidence
      of influenza A(H1N1) virus infection was present. Two children died as a result
      of their illness. The association of virus and gastrointestinal haemorrhage is
      explored.

PMID- 1988789
TI  - Are patients clients or people?

PMID- 1988790
TI  - Community resources and their use by general practitioners.

PMID- 1988791
TI  - School refusal.

PMID- 1988792
TI  - Insomnia.

PMID- 1988793
TI  - Methadone dosage and retention of patients in maintenance treatment.
AB  - Retention of patients in methadone treatment was studied in a cohort of 238
      heroin addicts who entered maintenance programmes between February 1986 and
      August 1987. All subjects had been assessed at a centralised unit and referred to
      one of two other units for maintenance. Of the ten client characteristics that we
      analysed, three--a history of imprisonment, a history of dependence on
      barbiturates or benzodiazepines and employment status at entry--were included
      with "clinic" and maximum dose of methadone in the Cox regression models.
      Allowing for the other four variables, the maximum daily dose of methadone
      dispensed during the study period was a highly significant predictor of retention
      (P less than 0.00001). With maximum dose stratified into three levels--less than
      60 mg, 60-79 mg, 80+ mg--and with the lowest stratum used as the baseline, the
      relative risk (RR) of leaving treatment was halved (RR 0.47, 95% confidence
      interval [CI] 0.33-0.67) for subjects receiving 60-79 mg, and halved again (RR
      0.21, 95% CI 0.12-0.38) for those who received 80+ mg. Clinic dosage policies
      contribute significantly to retention in methadone maintenance treatment. Clinics
      need to develop dosage policies in negotiation with individual patients.

PMID- 1988795
TI  - Dr Jack Kevorkian and medically assisted suicide. Assisting suicide sends a
      message.

PMID- 1988794
TI  - Anticonvulsants in pregnancy.
AB  - OBJECTIVE: To review the potential problems and their management associated with
      the use of anticonvulsant drugs during pregnancy. DATA SOURCES: Studies published
      between 1968 and 1990 assessing the effect of pregnancy on the pharmacokinetics
      of anticonvulsant drugs, the teratogenicity of anticonvulsants, breast feeding
      and anticonvulsants and use of the oral contraceptive pill in patients taking
      anticonvulsant medication, were reviewed. RESULTS OF DATA SYNTHESIS: In general,
      plasma levels fall during pregnancy and rise during the puerperium. A number of
      factors including possible reduced absorption, increased volume of distribution,
      reduced protein binding, increased clearance and noncompliance, contribute to
      this fall in plasma concentration. All anticonvulsants are potentially
      teratogenic. The incidence of fetal malformations is higher in patients treated
      with multiple anticonvulsant drugs and on higher dosages with higher plasma
      levels. Anticonvulsants are excreted in low concentrations in breast milk. All
      anticonvulsants except valproic acid have been associated with failure of the
      oral contraceptive pill. This is due to liver enzyme induction of these drugs.
      CONCLUSION: As plasma levels of anticonvulsants fall during pregnancy,
      concentrations should be monitored regularly. Due to the fall in protein binding,
      marginally low total plasma levels of highly protein bound drugs may not reflect
      reduced unbound levels, and hence an increase in dosage may not be required. In
      order to reduce teratogenicity, one should aim to use a single anticonvulsant
      drug and the lowest dosage able to achieve seizure control. In general, breast
      feeding is not contraindicated.

PMID- 1988796
TI  - Dr Jack Kevorkian and medically assisted suicide. Simple assistance and difficult
      issues.

PMID- 1988797
TI  - Privacy in medicine: issues old and new.

PMID- 1988799
TI  - The prediction of suicide.

PMID- 1988798
TI  - A case of Vibrio vulnificus septicaemia acquired in Victoria.
AB  - The clinical features and laboratory findings of a case of Vibrio vulnificus
      septicaemia are reported. The illness occurred in a previously well 68-year-old
      man who was accidentally spiked in the buttock by the dorsal spine of a flathead
      caught in Tamboon Inlet, near Mallacoota, Victoria. The clinical picture of an
      acute septicaemic illness with shock, associated with metastatic cellulitic
      lesions on the lower limbs progressing to bulla formation, skin necrosis,
      necrotising fasciitis and myositis, is characteristic of V. vulnificus
      septicaemia. It would appear that tetracyclines are the drugs of choice. Surgical
      debridement may be necessary. Clinical recognition of this rare but
      characteristic illness will facilitate early effective chemotherapy. To our
      knowledge this is the southern-most case reported in Australia.

PMID- 1988800
TI  - Pap smear and breast examination in the Sutherland district.

PMID- 1988801
TI  - Pneumonia caused by Haemophilus influenzae.

PMID- 1988802
TI  - Prisoners of conscience.

PMID- 1988803
TI  - Long-term survival after radical treatment for cancer of the oesophagus.

PMID- 1988804
TI  - Liver transplantation in children.

PMID- 1988805
TI  - Chronic meningococcal disease.

PMID- 1988806
TI  - Foreign medical graduates.

PMID- 1988807
TI  - Thiamine in our bread and wine.

PMID- 1988808
TI  - Anzac doctors.

PMID- 1988809
TI  - Women in science in Australia.

PMID- 1988810
TI  - Expo expirations: preparing our patients for travel.

PMID- 1988811
TI  - AIDS and RMOs.

PMID- 1988812
TI  - Free limb scheme.

PMID- 1988813
TI  - Horse-hair and asthma.

PMID- 1988814
TI  - Noblesse oblige.

PMID- 1988815
TI  - Prevention better than treatment of heart disease in China.

PMID- 1988816
TI  - Lobbying guide.

PMID- 1988817
TI  - Sulfhydryl compounds inhibit the cyto- and geno-toxicity of o-phenylphenol
      metabolites in CHO-K1 cells.
AB  - The effects of cysteine and reduced glutathione (GSH) on the genotoxicity of o
      phenylphenol (OPP) and its metabolites, phenylhydroquinone (PHQ) and
      phenylbenzoquinone (PBQ), were examined using the frequency of sister-chromatid
      exchanges (SCEs) and chromosome aberrations in CHO-K1 cells as parameters.
      Cytotoxic (cell-progression delay) and cytogenetic effects induced by a 3-h
      treatment with OPP, PHQ (100 micrograms/ml) or PBQ (50 micrograms/ml) with S9 mix
      after a 27-h expression time were inhibited by cysteine or GSH (3-10 mM).
      Materials corresponding to the cysteine or GSH adducts were found by HPLC in each
      incubation mixture. In the culture without S9 mix, PHQ and PBQ showed severe
      cytotoxicity since no metaphases could be obtained at doses over 25 and 5
      micrograms/ml, respectively, and the sulfhydryl compounds inhibited the toxicity
      by the formation of adducts with PBQ and by inhibiting the formation of PBQ in
      the case of PHQ. With PHQ, the sulfhydryl compounds appeared to inhibit
      autooxidation. However, the sulfhydryl compounds did not inhibit the cytotoxic
      and cytogenetic effects caused by OPP in the cell mixture without S9 mix, but on
      the contrary intensified them. No adduct formation was detected in the incubation
      solution. On the basis of these results, it is considered that electrophilic
      quinone (PBQ) and/or semiquinone (phenylsemiquinone, PSQ) radicals, capable of
      binding to nucleophilic small molecules (such as cysteine and GSH) or
      (biological) macromolecules, are produced from metabolite PHQ in metabolic
      oxidation of OPP, and induce cyto- and geno-toxic effects in the cells. The cyto-
      and geno-toxic effects of OPP itself to the cells are clearly independent of any
      electrophilic radical reaction.

PMID- 1988818
TI  - Clastogenicity of 1-nitropyrene, dinitropyrenes, fluorene and mononitrofluorenes
      in cultured Chinese hamster cells.
AB  - The chromosomal aberration test using a Chinese hamster lung cell line (CHL) was
      carried out on 1-nitropyrene (NP), 3 dinitropyrenes (DNPs), fluorene and 4
      mononitrofluorenes with and without metabolic activation (rat S9 mix). The 3 DNPs
      (1,3-, 1,6- and 1,8-DNP) induced chromosomal aberrations in the absence of S9
      mix. The frequencies of cells with aberrations after treatment for 48 h were 43%
      at 2 micrograms/ml of 1,3-DNP, 55% at 0.1 microgram/ml of 1,6-DNP and 45% at
      0.025 microgram/ml of 1,8-DNP, indicating the order of clastogenic potency as 1,8
      greater than 1,6- greater than 1,3-DNP. On the other hand, 1-NP, which is known
      to be a direct-acting mutagen in bacteria, was negative in the chromosomal
      aberration test without S9 mix, but clearly positive with S9 mix. This effect was
      dependent on the concentration of the S9 fraction in the reaction mixture. High
      pressure liquid chromatography analysis showed that 1-NP was converted by S9 mix
      to several metabolites, including 1-aminopyrene (AP). The clastogenic activity of
      1-AP, however, was equivocal without S9 mix, suggesting that active clastogens
      other than 1-AP exist. Fluorene induced chromosomal aberrations only in the
      presence of S9 mix (61.8% at 25 micrograms/ml). 1-, 2-, 3- and 4-nitrofluorene
      (NF) were more clastogenic in the presence of S9 mix than in the absence of S9
      mix, suggesting that NFs were converted to more active clastogens by S9 mix.

PMID- 1988820
TI  - Chromosomal aberrations in tuberculosis patients before and after treatment with
      short-term chemotherapy.
AB  - Cytogenetic effects of 4 common anti-tubercular drugs, isoniazid (H),
      streptomycin (S), rifampicin (R) and pyrazinamide (Z), in 3 different
      combinations (2 SHRZ, 2 HRZ and 2 H2R2Z2) were evaluated in the lymphocytes of
      tuberculosis patients undergoing chemotherapy, in order to estimate their
      mutagenic potential in combination. All 3 regimens showed an increased frequency
      of chromosomal aberrations after treatment compared to before treatment. These
      findings are of significance in the treatment of tuberculosis, as the drugs in
      question are observed to be mutagenic/clastogenic.

PMID- 1988819
TI  - Genotoxicity of 1-nitronaphthalene in Chinese hamster V79 cells.
AB  - 1-Nitronaphthalene (1-NN) has been identified in the U.S. National Toxicology
      Program as a non-carcinogen showing some evidence of in vitro genotoxicity. We
      tested this compound in Chinese hamster V79 cells at 20-80 micrograms/ml with two
      endpoints: sister-chromatid exchange (SCE) and thioguanine resistance (TGR), with
      5 repeat experiments. The SCE values in the presence of rat or hamster
      hepatocytes were consistently above the 95% and usually the 99% upper confidence
      limits for the corresponding control. Without hepatocyte activation, the control
      upper confidence limits were not exceeded except in one experiment in which the
      control SCE value was unusually low. TGR was scored both as proportion of plates
      with mutant colonies and as number of mutant colonies per plate. In 2 of 5
      experiments, these values exceeded control 95% or 99% upper confidence limits; on
      the other hand, these values were substantially lower than those of the positive
      controls, dimethylbenz[a]anthracene (2.6 micrograms/ml) with activation and ethyl
      methanesulfonate (155 microgram/ml), which is direct-acting. For TGR, activation
      of 1-NN by either rat or hamster hepatocytes produced inconsistent results.
      Overall we would consider this compound to be a weak genotoxin, to which a cancer
      bioassay would be expected to be relatively insensitive.

PMID- 1988821
TI  - Further studies on the comutagenic activity of cigarette smoke condensate.
AB  - The comutagenic effect exerted by cigarette smoke condensate (CSC) was
      investigated. In vitro experiments with Salmonella typhimurium strains TA98 and
      TA98/1.8DNP6 indicated that CSC specifically enhances the mutagenicity of
      polyaromatic amines such as 2-aminofluorene, 2-acetylaminofluorene, 4
      acetylaminofluorene and 2-aminoanthracene. The pattern of comutagenicity of CSC
      was shown to differ from that of norharman, a tobacco-related known comutagenic
      substance. Both black and blond tobacco CSCs proved to interact synergistically
      with 2-aminoanthracene mutagenicity. Chemical fractionation of CSC indicates the
      occurrence of comutagenic substance(s) in both neutral and basic components.
      Further in vitro experiments with 2-acetylaminofluorene metabolites and
      derivatives suggest that the comutagenic effect of CSC could involve later
      step(s) in the metabolic activation of fluorenylamines, i.e., the conversion of
      hydroxylamines into ultimate reactive species. The possible occurrence of a
      synergistic interaction of CSC with chemical mutagens in vivo was evaluated.
      Administration of 2-aminoanthracene/CSC mixtures, previously shown to be
      comutagenic in vitro, failed to demonstrate a synergistic effect in SCE induction
      in bone marrow cells of mice. This apparent discrepancy may rely on divergences
      in the activation pathways of polycyclic amines in vitro and in vivo.

PMID- 1988822
TI  - Forward mutation of S. typhimurium by smokeless tobacco extracts.
AB  - Mutagenicity of 4 popular brands of smokeless tobaccos was studied using a S.
      typhimurium forward mutation assay. Aqueous extracts of 4 brands and
      dichloromethane and methanol extracts of 1 of the 4 brands of smokeless tobacco's
      did not induce significant mutagenicity either in the presence or absence of
      metabolic activation. Aqueous and organic extracts were however mutagenic when
      treated with physiological levels of sodium nitrite (0.25 mM) at acidic pH and
      without metabolic activation. The results indicate that smokeless tobacco contain
      polar and non-polar chemicals which become mutagenic to S. typhimurium under
      nitrosation conditions.

PMID- 1988824
TI  - Mitosis-arresting effects of cigarette smoke condensate on human lymphoid cell
      lines.
AB  - Whole-smoke condensates from the University of Kentucky reference cigarettes
      induced partial mitotic arrest in 4 human lymphoid cell lines. Treatment of cells
      for 3 h with 100 and 200 micrograms of cigarette-smoke condensate/ml of culture
      medium increased the frequency of metaphases and decreased the proportion of
      anaphases in the treated cell populations. Cytoskeletal studies using antitubulin
      immunofluorescence techniques and transmission electron microscopic studies
      demonstrated that in early stages of mitosis the formation of aster and the
      separation of centrosomes in condensate-treated cells were comparable to those of
      untreated control cells, but the poleward migration of centrosomes was inhibited.
      Arrested metaphases revealed two centrosomes surrounded by aggregated chromosomes
      in the center of each cell but the structure of the centrioles, microtubules and
      the kinetochores appeared normal. The results demonstrate the presence of
      antimitotic compounds in the tobacco-smoke condensate.

PMID- 1988823
TI  - Liver, lung and kidney homogenates used as an activation system in mutagenicity
      studies of airborne particles and of expectorate and urine samples from exposed
      workers in a coke plant.
AB  - A comparison was made between lung and kidney homogenates on the one hand and
      liver S9 from rats on the other hand in order to compare their ability to
      activate promutagens. The Salmonella reversion assay was used on extracts of
      airborne particles from the top of coke oven batteries, and of expectorate and
      urine samples from exposed workers in the same coke plant. The contents of
      benzo[a]anthracene and benzo[a]pyrene in the different test solutions were
      measured by high-resolution gas chromatography/mass spectrometry. Both mutagens
      were detected in the filter extract and in the expectorates from the exposed
      workers but not in the expectorates from the control groups or in the urine
      samples. The liver S9 gave significantly higher mutagenicity than lung and kidney
      activation with both filter samples and expectorate and urine samples.

PMID- 1988825
TI  - A comparison of the relative activities of 8 radiosensitizers in the SOS
      chromotest.
AB  - Misonidazole, and RSU 1069 and 6 of its analogues are all reported to show
      increased cytotoxicity towards hypoxic cells compared to oxic cells. DNA is
      considered to be the target through which these drugs exert their cytotoxic
      activity. Therefore we monitored induction of the SOS response in uvrABC
      excinuclease proficient and deficient strains of E. coli, under oxic and hypoxic
      conditions, as an indirect method of assessing the activity of these drugs
      towards DNA in a biological system. This was done using the SOS chromotest which
      utilizes E. coli strains which possess a sfiA::lacZ fusion allowing induction of
      the SOS response to be monitored by assaying beta-galactosidase activity. All of
      the drugs tested here show some induction of the SOS response in both uvrABC
      excinuclease proficient and deficient strains. Data shown here suggests that the
      uvrABC excinuclease is important in the production of a SOS induction signal from
      RSU 1069-induced DNA lesions and that RSU 1069 may act as a crosslinking agent.
      The data also shows that SOS induction activity and toxicity do not necessarily
      correlate and that production of a SOS induction signal may occur via a different
      pathway for RSU 1069 than for its analogues.

PMID- 1988826
TI  - Mutagenicity of 30 chemicals in Salmonella typhimurium strains possessing
      different nitroreductase or O-acetyltransferase activities.
AB  - Salmonella typhimurium YG1021, YG1024, YG1026 and YG1029 are new derivatives of
      the Ames tester strains TA98 and TA100, with elevated 'classical' nitroreductase
      or acetyl-CoA:N-hydroxyarylamine O-acetyltransferase level. Thirty mutagens with
      different structures were tested using these strains and the sensitivities were
      compared with those of the conventional strains and of the enzyme-deficient
      strains. Elevated O-acetyltransferase activity of the indicator strains
      specifically increased their ability to detect the mutagenicity of aromatic
      nitro, amino and hydroxylamino compounds, whereas the strains with high
      nitroreductase activity were very sensitive to some nitroaromatics. The combined
      use of the isogenic tester strains with different metabolic capacities was quite
      useful to assess the intracellular metabolic activation and detoxification
      mechanisms of chemical mutagens.

PMID- 1988827
TI  - Treatment of gram-negative bacteremia and septic shock with HA-1A human
      monoclonal antibody against endotoxin. A randomized, double-blind, placebo
      controlled trial. The HA-1A Sepsis Study Group.
AB  - BACKGROUND: HA-1A is a human monoclonal IgM antibody that binds specifically to
      the lipid A domain of endotoxin and prevents death in laboratory animals with
      gram-negative bacteremia and endotoxemia. METHODS: To evaluate the efficacy and
      safety of HA-1A, we conducted a randomized, double-blind trial in patients with
      sepsis and a presumed diagnosis of gram-negative infection. The patients received
      either a single 100-mg intravenous dose of HA-1A (in 3.5 g of albumin) or placebo
      (3.5 g of albumin). Other interventions, including the administration of
      antibiotics and fluids, were not affected by the study protocol. RESULTS: Of 543
      patients with sepsis who were treated, 200 (37 percent) had gram-negative
      bacteremia as proved by blood culture. For the patients with gram-negative
      bacteremia followed to death or day 28, there were 45 deaths among the 92
      recipients of placebo (49 percent) and 32 deaths among the 105 recipients of HA
      1A (30 percent; P = 0.014). For the patients with gram-negative bacteremia and
      shock at entry, there were 27 deaths among the 47 recipients of placebo (57
      percent) and 18 deaths among the 54 recipients of HA-1A (33 percent; P = 0.017).
      Analyses that stratified according to the severity of illness at entry showed
      improved survival with HA-1A treatment in both severely ill and less severely ill
      patients. Of the 196 patients with gram-negative bacteremia who were followed to
      hospital discharge or death, 45 of the 93 given placebo (48 percent) were
      discharged alive, as compared with 65 of the 103 treated with HA-1A (63 percent;
      P = 0.038). No benefit of treatment with HA-1A was demonstrated in the 343
      patients with sepsis who did not prove to have gram-negative bacteremia. For all
      543 patients with sepsis who were treated, the mortality rate was 43 percent
      among the recipients of placebo and 39 percent among those given HA-1A (P =
      0.24). All patients tolerated HA-1A well, and no anti-HA-1A antibodies were
      detected. CONCLUSIONS: HA-1A is safe and effective for the treatment of patients
      with sepsis and gram-negative bacteremia.

PMID- 1988828
TI  - Diagnostic relevance of clonal cytogenetic aberrations in malignant soft-tissue
      tumors.
AB  - BACKGROUND: Malignant soft-tissue tumors often present substantial diagnostic
      challenges. Chromosome aberrations that might be diagnostic have been identified
      in some types of soft-tissue tumors, but the overall frequency and diagnostic
      relevance of these aberrations have not been established. METHODS: We attempted
      to determine the karyotypes of a series of 62 consecutive, unselected malignant
      spindle-cell or small round-cell soft-tissue tumors (from 46 adults and 16
      children) after direct harvesting of cells or short-term culture. All tumors were
      examined independently by immunohistochemical staining in addition to routine
      light-microscopical evaluation, and all but two tumors were examined by electron
      microscopy. RESULTS: Metaphases were obtained from 61 of the 62 tumors, and
      clonal chromosome aberrations were identified in 55 (89 percent). In the six
      tumors that yielded metaphases but lacked apparent clonal aberrations, the normal
      metaphases were found to originate from non-neoplastic stromal elements within
      the tumor specimens. Thus, all tumors in which karyotyping was successful
      contained clonal chromosome aberrations. Forty of 62 tumors (65 percent)
      contained clonal chromosome aberrations that either suggested or confirmed a
      specific diagnosis; in 15 of these tumors (24 percent of all tumors), the
      aberrations were important in establishing the final diagnosis. Cytogenetic
      analyses were particularly informative about small round-cell tumors from
      children: 8 of 14 round-cell tumors contained diagnostically important chromosome
      aberrations. Using the combined approaches of light and electron microscopy,
      immunohistochemistry, and cytogenetics, we established an unambiguous diagnosis
      for 60 of 62 tumors. CONCLUSIONS: Cytogenetic analyses reveal clonal chromosome
      aberrations in virtually all malignant soft-tissue tumors. These clonal
      chromosome aberrations, particularly in small round-cell tumors in children,
      often have diagnostic relevance.

PMID- 1988829
TI  - A controlled trial comparing vidarabine with acyclovir in neonatal herpes simplex
      virus infection. Infectious Diseases Collaborative Antiviral Study Group.
AB  - BACKGROUND: Despite the use of vidarabine, herpes simplex virus (HSV) infection
      in neonates continues to be a disease of high morbidity and mortality. We
      undertook a controlled trial comparing vidarabine with acyclovir for the
      treatment of neonatal HSV infection. METHODS: Babies less than one month of age
      with virologically confirmed HSV infection were randomly and blindly assigned to
      receive either intravenous vidarabine (30 mg per kilogram of body weight per day;
      n = 95) or acyclovir (30 mg per kilogram per day; n = 107) for 10 days. Actuarial
      rates of mortality and morbidity among the survivors after one year were compared
      overall and according to the extent of the disease at entry into the study
      (infection confined to the skin, eyes, or mouth; encephalitis; or disseminated
      disease). RESULTS: After adjustment for differences between groups in the extent
      of disease, there was no difference between vidarabine and acyclovir in either
      morbidity (P = 0.83) or mortality (P = 0.27). None of the 85 babies with disease
      confined to the skin, eyes, or mouth died. Of the 31 babies in this group who
      were treated with vidarabine and followed for a year, 88 percent (22 of 25) were
      judged to be developing normally after one year, as compared with 98 percent (45
      of 46) of the 54 treated with acyclovir (95 percent confidence interval for the
      difference, -4 to 24). For the 71 babies with encephalitis, mortality was 14
      percent with vidarabine (5 of 36) and with acyclovir (5 of 35); of the survivors,
      43 percent (13 of 30) and 29 percent (8 of 28), respectively, were developing
      normally after one year (95 percent confidence interval for the difference, -11
      to 39). For the 46 babies with disseminated disease, mortality was 50 percent (14
      of 28) with vidarabine and 61 percent (11 of 18) with acyclovir (95 percent
      confidence interval for the difference, -20 to 40); of the survivors, 58 percent
      (7 of 12) and 60 percent (3 of 5), respectively, were judged to be developing
      normally after one year (95 percent confidence interval for the difference, -40
      to 50). Both medications were without serious toxic effects. CONCLUSIONS: In this
      multicenter, randomized, blinded study there were no differences in outcome
      between vidarabine and acyclovir in the treatment of neonatal HSV infection. The
      study lacked statistical power to determine whether there were sizable
      differences within the subgroups of those with localized HSV, encephalitis, or
      disseminated disease.

PMID- 1988830
TI  - Predictors of morbidity and mortality in neonates with herpes simplex virus
      infections. The National Institute of Allergy and Infectious Diseases
      Collaborative Antiviral Study Group.
AB  - BACKGROUND: In a controlled trial comparing acyclovir with vidarabine in the
      treatment of neonatal herpes simplex virus (HSV) infection, we found no
      significant difference between the treatments in adjusted mortality and
      morbidity. Hence, we sought to define for the entire cohort (n = 202) the
      clinical characteristics that best predicted the eventual outcome in these
      neonates. METHODS: Data were gathered prospectively at 27 centers between 1981
      and 1988 in infants less than one month of age who had virologically confirmed
      HSV infection. We examined the outcomes by multivariate analyses of 24 variables.
      Disease was classified in one of three categories based on the extent of the
      involvement at entry into the trial: infection confined to skin, eyes, or mouth;
      encephalitis; or disseminated infection. RESULTS AND CONCLUSIONS: There were no
      deaths among the 85 infants with localized HSV infection. The mortality rate was
      significantly higher in the 46 neonates with disseminated infection (57 percent)
      than in the 71 with encephalitis (15 percent). In addition, the risk of death was
      increased in neonates who were in or near coma at entry (relative risk, 5.2), had
      disseminated intravascular coagulopathy (relative risk, 3.8), or were premature
      (relative risk, 3.7). In babies with disseminated disease, HSV pneumonitis was
      also associated with greater mortality (relative risk, 3.6). In the survivors,
      morbidity was most frequent in infants with encephalitis (relative risk, 4.4),
      disseminated infection (relative risk, 2.1), seizures (relative risk, 3.0), or
      infection with HSV type 2 (relative risk, 4.9). With HSV infection limited to the
      skin, eyes, or mouth, the presence of three or more recurrences of vesicles was
      associated with an increased risk of neurologic impairment as compared with two
      or fewer recurrences.

PMID- 1988831
TI  - Syncytial giant-cell hepatitis. Sporadic hepatitis with distinctive pathological
      features, a severe clinical course, and paramyxoviral features.
AB  - BACKGROUND AND METHODS: We describe a new form of hepatitis, occurring in 10
      patients over a period of six years, characterized clinically by manifestations
      of severe hepatitis, histologically by large syncytial giant hepatocytes, and
      ultrastructurally by intracytoplasmic structures consistent with paramyxoviral
      nucleocapsids. RESULTS: The patients ranged in age from 5 months to 41 years. The
      tentative clinical diagnosis before biopsy was non-A, non-B hepatitis in five
      patients and autoimmune chronic active hepatitis in the others. Five patients
      underwent liver transplantation; the others died. The diagnosis of syncytial
      giant-cell hepatitis was established pathologically. The liver cords were
      replaced in all 10 patients by syncytial giant cells with up to 30 nuclei. In 8
      of the 10 the cytoplasm contained pleomorphic particles of 150 to 250 microns,
      filamentous strands, and particles of 14 to 17 nm with peripherally disposed
      spikes resembling paramyxoviral nucleocapsids. Structures resembling degenerated
      forms were found in the other two patients. One of two chimpanzees injected with
      a liver homogenate from the index patient had an increase in the titer of
      paramyxoviral antibodies, probably an anamnestic reaction to previous
      paramyxoviral infection, suggesting that a paramyxoviral antigen but not viable
      virus was present in the liver homogenate. CONCLUSIONS: Although further
      virologic studies will be required for precise classification, we believe that
      paramyxoviruses should be considered in patients with severe sporadic hepatitis.

PMID- 1988832
TI  - Common solid tumors of childhood.

PMID- 1988833
TI  - Increased chloride reabsorption as an inherited renal tubular defect in familial
      type II pseudohypoaldosteronism.

PMID- 1988834
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 7-1991. A 21-year-old woman with a persistent rash on the elbow
      after a sojourn in Central America.

PMID- 1988835
TI  - Monoclonal antibodies and the treatment of gram-negative bacteremia and shock.

PMID- 1988836
TI  - Hypoaldosteronism--disease or normal response?

PMID- 1988837
TI  - Clozapine and the mandatory monitoring system.

PMID- 1988838
TI  - Early neurologic abnormalities in HIV infection.

PMID- 1988839
TI  - MRI and ultrasonography in staging prostate cancer.

PMID- 1988840
TI  - Neurally mediated syncope and atrial fibrillation.

PMID- 1988842
TI  - Job turnover--a problem with employer-based health care.

PMID- 1988841
TI  - Case 23-1990--giant-cell arteritis.

PMID- 1988844
TI  - The day Kuwait was invaded by Iraq.

PMID- 1988843
TI  - Germany's health care system (1)

PMID- 1988845
TI  - Product-line management and competition.

PMID- 1988846
TI  - The role of chief nursing executive in a true product-line environment.

PMID- 1988847
TI  - The application of total quality management concepts in a service-line
      cardiovascular program.

PMID- 1988848
TI  - Case management: a product line.

PMID- 1988850
TI  - Automation: the key to successful product-line management.

PMID- 1988849
TI  - Product-line management: threat or opportunity for nursing?

PMID- 1988851
TI  - Hoag Memorial Hospital. Product-line management through organizational redesign.

PMID- 1988852
TI  - Hoag Memorial Hospital. The product-line management team.

PMID- 1988853
TI  - Positioning your nursing organization for product-line structure.

PMID- 1988854
TI  - The strategic management of quality.

PMID- 1988856
TI  - Pragmatic strategies for product-line management.

PMID- 1988855
TI  - PRO/nurse: an autonomous incentive-based concept.

PMID- 1988857
TI  - Getting along with co-workers better.

PMID- 1988858
TI  - Learning from Neil.

PMID- 1988859
TI  - Two eye-opening errors.

PMID- 1988860
TI  - Understanding acute tubular necrosis.

PMID- 1988861
TI  - Assessing elevated potassium values.

PMID- 1988862
TI  - Noninvasive pacing: what you should know.

PMID- 1988864
TI  - New trends in charting.

PMID- 1988863
TI  - Are you ready for ventilator patients?

PMID- 1988865
TI  - Making the grade.

PMID- 1988866
TI  - Helping stressed families on an I.C.U.

PMID- 1988867
TI  - Do you need professional liability insurance?

PMID- 1988868
TI  - Administering intraperitoneal chemotherapy. A new approach.

PMID- 1988869
TI  - Managing the seizure patient.

PMID- 1988870
TI  - We did everything we could for Matt and he got well in spite of it.

PMID- 1988871
TI  - Antibiotics and colitis. Toxic combination.

PMID- 1988872
TI  - Mrs. Corey's final hour.

PMID- 1988873
TI  - Metoprolol for myocardial infarction.

PMID- 1988874
TI  - 6 steps for keeping your spirit strong.

PMID- 1988875
TI  - Spontaneous rupture of liver during pregnancy: current therapy.
AB  - Spontaneous hepatic rupture secondary to severe pregnancy-induced hypertension is
      associated with a high rate of maternal and fetal mortality. Numerous types of
      surgical management have been described, but a uniform surgical approach has not
      been accepted. The purpose of this review was to examine modes of surgical
      therapy reported in the literature since 1976, as well as the 11-year experience
      at our institution. Twenty-eight cases were extracted from the literature and
      seven more were identified at our institution. The incidence in our population
      was one per 45,145 live births. Among 27 cases managed by packing and drainage,
      an 82% overall survival was achieved, whereas only 25% of eight patients
      undergoing hepatic lobectomy survived (P = .006). Hepatic hemorrhage with
      persistent hypotension unresponsive to blood products should be managed by
      evacuating the hematoma, packing the damaged liver, and draining the operative
      site. More aggressive surgical techniques, such as hepatic artery ligation or
      hepatic lobectomy, should be reserved for refractory cases.

PMID- 1988876
TI  - C-reactive protein in normal pregnancy.
AB  - Maternal serum C-reactive protein (CRP) has been studied extensively as an
      adjunct in the diagnosis of subclinical infection among pregnant women with
      preterm labor or preterm rupture of membranes. However, before the utility of CRP
      can be studied in pregnancies with these complications, the effects of normal
      pregnancy and labor on maternal serum CRP levels must be established. We
      determined CRP levels serially from 22 weeks' gestation until delivery in healthy
      pregnant women without antepartum complications. Median CRP values for women not
      in labor ranged from 0.7-0.9 mg/dL, depending on gestational age; 95% of the
      values were 1.5 mg/dL or lower. No consistent change in CRP levels with
      gestational age was found among serially sampled women not in labor. The median
      CRP value for women in labor at term was 1.3 mg/dL, and 32% of values were over
      1.5 mg/dL. Median CRP values in normal pregnancies appear to be higher than
      standardized values for nonpregnant individuals, and CRP values are further
      elevated in labor. Understanding the physiology and temporal course of the
      increase in CRP in normal pregnancy and labor may help to clarify the appropriate
      use of CRP in complicated pregnancies.

PMID- 1988877
TI  - Comparison of the accuracy of glucose reflectance meters in pregnant insulin
      dependent diabetics.
AB  - Home monitoring of blood glucose by reflectance meters has been shown to be
      accurate in the nonpregnant diabetic and is currently used for outpatient glucose
      control in the pregnant diabetic as well. Beckman ASTRA glucose results from
      samples collected into sodium fluoride were used as the standard for this study.
      Comparisons were then made to four glucose reflectance meters: Accu-Check II, One
      Touch, DiaScan S, and ExacTech. Although the reflectance meters appeared to be
      useful for assessing blood glucose trends in the pregnant diabetic, the results
      obtained from these meters would be unacceptable in the laboratory setting.
      Unfortunately, because of the erratic combination of proportional and constant
      bias, correction factors are not easily ascertained. Laboratories and physicians
      should reconsider the use of these reflectance meters for inpatient evaluation
      and general population screening of pregnant women.

PMID- 1988878
TI  - Urinary sediment changes in severe preeclampsia.
AB  - We analyzed the urinary sediment of 30 patients with severe preeclampsia every 4
      hours during early labor, delivery, and the postpartum period. Fifteen normal
      control patients were also followed in a similar fashion. No casts were noticed
      in the urine samples of the control group. However, the urinary sediment of
      preeclamptic patients revealed the same uniform pattern regardless of the state
      of coagulation, or the presence or absence of oliguria or eclamptic seizures.
      Numerous granular and hyaline casts, red-cell, and tubular cell casts were
      identified during microscopic evaluation. These data reflect both glomerular and
      tubular damage in preeclampsia. We conclude that urinary sediment analysis in
      severe preeclampsia uniformly reflects renal parenchymal damage and does not
      correlate with or predict the clinical course of the disease.

PMID- 1988879
TI  - The relationship between maternal hematocrit and pregnancy outcome.
AB  - The relationship between maternal hematocrit and pregnancy outcome at various
      times in pregnancy was studied in 17,149 iron- and folate-supplemented pregnant
      women. On univariate analysis, early-pregnancy hematocrits below 37% were
      associated with preterm delivery. However, this relationship was not confirmed by
      multivariate analysis controlling for other risk factors. On both univariate and
      multivariate analyses, both early and later in pregnancy, hematocrits above 40%
      were associated with preterm delivery. In every gestational time period, at least
      part of the excess of preterm births was explained by an increase in indicated
      preterm deliveries. In both early and late pregnancy, and in both the univariate
      and multivariate analyses, only high hematocrits were associated with fetal
      growth retardation. The strongest association (odds ratio above 2) between high
      hematocrit and both fetal growth retardation and preterm delivery occurred with
      hematocrits at or above 43% at 31-34 weeks' gestation.

PMID- 1988881
TI  - The effect of lateral tilt on maternal and fetal hemodynamic variables.
AB  - We measured maternal blood pressure and heart rate, fetal heart rate, and
      umbilical artery velocity waveforms in 25 healthy women placed in the supine and
      in both right and left 5 degrees and 10 degrees lateral tilt positions. Although
      we found no significant difference among these variables in the various maternal
      positions, two of 25 women became hypotensive and symptomatic in the supine and 5
      degrees tilt positions. Because we could not predict which women would become
      symptomatic, we recommend lateral tilt of all pregnant women during operative
      procedures beyond 20 weeks' gestation, including those in the lithotomy position
      for vaginal delivery.

PMID- 1988880
TI  - Cesarean: changing the trends.
AB  - A rising cesarean birth rate, both nationally and at our institution, led us to
      attempt to reverse the trend. Vaginal birth after cesarean (VBAC) was introduced
      as an alternative to repeat cesarean in 1982. The impact of VBAC on the cesarean
      rate for our institution was assessed from 1982-1988. Over the period studied,
      the rate of repeat cesarean rose from 5.0% in 1982 to 6.9% in 1985, then steadily
      fell to 5.3% in 1988. During this same period, the primary cesarean rate rose
      from 7.5% in 1982 to 11.9% in 1986, then declined to 10.6% in 1988. Changes in
      the rate for all cesareans paralleled those for primary procedures: 12.5% in
      1982, 17.6% in 1986, and 15.9% in 1988. In patients with a history of previous
      cesarean, the relative risk of repeat cesarean dropped from 10.2 (95% confidence
      interval 8.8-11.8) in 1982 to 5.2 (95% confidence interval 4.5-6.0) in 1988. In
      the face of a rising rate of primary cesarean births, the introduction of VBAC
      has helped to stabilize the overall cesarean rate at our institution.

PMID- 1988882
TI  - A comparison of Doppler flow velocity waveforms, amniotic fluid columns, and the
      nonstress test as a means of monitoring post-dates pregnancies.
AB  - Five hundred thirty-four pregnancies exceeding 294 days were monitored by weekly
      sonographic estimations of amniotic fluid columns, daily maternal recordings of
      fetal movements, and thrice-weekly nonstress tests. In addition, each woman
      received twice-weekly studies of the uteroplacental and umbilical circulations by
      means of Doppler ultrasound. There were no fetal deaths in the study. Of the
      individual methods of fetal surveillance, absence of end-diastolic frequencies in
      the umbilical artery was the most sensitive, predicting 91% of fetuses who
      developed fetal distress in the first stage. Combining the test with sonographic
      estimation of amniotic fluid columns improved the prediction to 100%, with only a
      minimal fall in the specificity. These results strongly suggest that a
      combination of umbilical artery Doppler waveforms and amniotic fluid
      determinations is an adequate method of monitoring the post-dates pregnancy.

PMID- 1988883
TI  - Measurement of systolic-diastolic ratio in the umbilical artery by continuous
      wave and pulsed-wave Doppler ultrasound: comparison at different sites.
AB  - Analysis of umbilical artery flow velocity waveforms, especially systolic
      diastolic (S-D) ratio, can predict some pregnancy abnormalities. Most of the
      earlier studies did not specify the exact segment of umbilical artery sampled. We
      studied 53 normal singleton pregnancies between 18-41 weeks' gestation to compare
      S-D ratio measurements of the umbilical artery at different sites: 1) abdominal
      insertion site, 2) placental insertion site, 3) mid-cord, and 4) an undetermined
      site. The mean S-D ratio was significantly different (P less than .01) at various
      segments of the umbilical artery--higher near the abdominal insertion site when
      compared with the mid-cord, near-placental, and undetermined sites. The S-D ratio
      at mid-cord was higher than at the undetermined site and the placental insertion
      site. The near-placental-site S-D ratio was not different from the undetermined
      site. A lower S-D ratio at the undetermined site may not adequately reflect the
      true physiologic status of the fetus. Specifying the site of measurement should
      be an integral part of any report, in order to describe accurately the
      pathophysiology of fetoplacental circulatory diseases.

PMID- 1988884
TI  - Doppler velocimetry in prolonged pregnancy.
AB  - Eighty-two patients at 287 days' gestation or longer were tested by nonstress
      test (NST), amnioscopy, ultrasound assessment of amniotic fluid volume, and
      Doppler velocimetry. Several maternal and fetal arteries were analyzed: uterine,
      umbilical, descending thoracic aorta, renal, and middle cerebral. During the
      study, other maternal-fetal functional indices were recorded: hPL, estriol,
      hematocrit, platelets, mean platelet volume, and uric acid. No abnormalities were
      found in the uterine, umbilical, middle cerebral, thoracic descending aorta, and
      renal artery velocimetry in post-dates gestations. However, a significant
      reduction of the time-averaged mean velocity in the descending thoracic aorta was
      associated with an increased incidence of oligohydramnios, meconium-stained
      fluid, abnormal NST, and cesarean delivery for fetal distress. The present study
      suggests that serial Doppler flow measurements of mean velocity of the fetal
      descending thoracic aorta may be a simple and rapid technique for identifying
      prolonged pregnancies at increased risk for perinatal complications.

PMID- 1988885
TI  - Doppler systolic-diastolic ratios in pregnancies complicated by syphilis.
AB  - Maternal infection with syphilis can result in focal areas of vasculitis and,
      similarly, placental villitis and obliterative arteritis. We hypothesized that
      Doppler systolic-diastolic ratios (S/Ds) in pregnancies complicated by maternal
      syphilis infection might reflect an increased resistance to placental perfusion.
      Doppler velocity waveform analysis was used to study the uterine and umbilical
      arteries in third-trimester pregnancies complicated by maternal syphilis
      infection. A control group of similarly studied normal pregnancies was used for
      comparison. Statistically significant increases were found in the mean S/Ds of
      both the uterine and umbilical arteries in the syphilis group compared with the
      normal group, indicating an increased resistance to perfusion of the placenta in
      pregnancies complicated by syphilis. This difference was even greater in
      association with the identification of spirochetes in the amniotic fluid by dark
      field microscopy, indicating that the S/D results are related to the presence of
      intrauterine infection. Serial S/Ds in a small subgroup of patients correlated
      with the clinical courses, including an apparent acute vascular-resistance change
      associated with treatment, probably due to the Jarisch-Herxheimer reaction.
      Because of these post-treatment vascular events, the pre-treatment S/D alone may
      have a limited clinical predictive value for treatment efficacy in congenital
      syphilis.

PMID- 1988886
TI  - Low incidence of positive amnionic fluid cultures in preterm labor at 27-32 weeks
      in the absence of clinical evidence of chorioamnionitis.
AB  - In order to determine the utility of amniocentesis for detecting subclinical
      chorioamnionitis in asymptomatic afebrile women in preterm labor with intact
      membranes, we enrolled 47 women between 27-32 weeks' gestation in a prospective
      study. After enrollment, 38 women fulfilled all clinical and laboratory criteria
      for the study; nine women were excluded because they had a leukocyte count
      exceeding 15,000/microL. None of the 38 asymptomatic afebrile women had a
      positive culture from the amnionic fluid for bacteria, fungi, Mycoplasma hominis,
      Ureaplasma urealyticum, Chlamydia trachomatis, or any viruses. Sepsis was not
      proved in any of the 38 infants delivered to these patients. There was a clear
      relationship between histologic evidence of chorioamnionitis and failure of
      tocolytic therapy. Fetal lung profiles were mature in 29% of the amnionic fluid
      samples from 30-32 weeks' gestation, but in none of the amnionic fluid samples
      before 30 weeks. Amniocentesis does not seem useful to detect chorioamnionitis in
      asymptomatic afebrile women with preterm labor and intact membranes at 27-32
      weeks' gestation, and should be reserved for those cases in which information
      about fetal lung maturity would be helpful.

PMID- 1988887
TI  - Ipsilateral versus contralateral ovary selection of dominant follicle in
      succeeding cycle.
AB  - There is still confusion as to whether ovulation in a succeeding cycle is a
      random event or is more likely to occur at the ipsilateral or contralateral
      ovary. Both histologic and sonographic data support alternating ovulation. Some
      ultrasound studies have suggested that ipsilateral ovulation is more likely in
      succeeding cycles, and another found right-sided ovulation to be more common.
      Because many of the studies are based upon small numbers, we initiated a large
      study to determine the more likely side of ovulation. Furthermore, the present
      investigation attempted to confirm biochemically the true existence of the
      dominant follicle by demonstrating appropriate serum estradiol levels. Evaluation
      of natural cycles (286 pairs) demonstrated 52.4% ipsilateral ovulation and 47.6%
      contralateral ovulation. Right-sided ovulation occurred in 54.5% of cycles. Our
      data suggest that the side of ovulation in successive cycles is not influenced by
      the side of ovulation in the preceding cycle.

PMID- 1988889
TI  - Endotoxin in vaginal fluid of women with bacterial vaginosis.
AB  - The concentration of endotoxin in vaginal fluid was measured in 19 women with
      bacterial vaginosis and in nine controls with normal vaginal flora. The vaginal
      fluid of the women with bacterial vaginosis contained significantly greater
      amounts of endotoxin: 0.308 +/- 0.396 versus 0.008 +/- 0.002 endotoxin units/mg
      vaginal fluid. Endotoxin in vaginal fluid may contribute to the activation of the
      prostaglandin system, which could provoke premature labor.

PMID- 1988888
TI  - Fertility rates in men with normal semen characteristics: spermatozoal testing by
      induction of the acrosome reaction and Wright-Giemsa staining for subtle abnormal
      forms.
AB  - Little is known about the fertility potential of semen from men who fulfill the
      accepted criteria of normal semen quality. We examined retrospectively the
      fertility rates of semen donors with normal semen quality. Donor performance was
      evaluated in women who had no known infertility factors or had only ovulatory
      dysfunction corrected by clomiphene. Cycles of therapeutic donor insemination
      were monitored for ovulation, and pregnancy outcome was followed up. Pregnancy
      resulted from therapeutic donor insemination with 21 donors and did not result in
      pregnancy with five (the range of the percentage of cycles in which pregnancy
      occurred was zero to 31). The comparison of donor semen analysis characteristics
      with pregnancy rates indicated that the total number of motile spermatozoa per
      ejaculate correlated with pregnancy rate (P = .04). Cox proportional hazard
      regression analysis showed that when the value for percentage of abnormal forms
      was combined with the total number of motile spermatozoa, a significant negative
      association was found between abnormal forms and conception (P = .04).
      Experiments comparing semen from high-fertility donors (top quartile of pregnancy
      rate) and low-fertility donors (lowest quartile) demonstrated a greater
      proportion of spermatozoa with inducible acrosome reactions in the high-fertility
      group (P less than .05). A Wright-Giemsa stain used to detect subtle abnormal
      forms in spermatozoa did not discriminate between the groups. These data suggest
      that differences in fertility potential exist among donors, even though all may
      exceed the accepted criteria for normal semen quality. Differences in the ability
      of spermatozoa to capacitate or undergo the acrosome reaction may be a mechanism
      for diminished fertility in donors with normal semen characteristics.

PMID- 1988890
TI  - Persistent tubal pregnancy.
AB  - Persistent tubal pregnancy may be manifest by either acute symptoms or a
      persistent or rising beta-hCG titer following conservative surgery. This
      condition is a relatively new complication, related to the recent practice of
      conservative surgical management of tubal pregnancy. Much has been written on the
      identification and possible therapy for this condition but little is known about
      its pathophysiology. Eight cases of persistence were studied, as well as three
      cases of failed conservative procedures. In nine instances, the surgeon had
      concentrated appropriately on the maximally dilated portion of the tube, which
      contained the blood clot and aborted products of conception. Unfortunately, the
      implantation site was located medially, toward the uterus. Ways of avoiding this
      complication include medial exploration or possibly the use of mesosalpingeal
      injection of vasopressin. An understanding of the natural history of the
      pathologic process might also be valuable in the management of cases of
      "persistence" identified solely by a continuing beta-hCG titer.

PMID- 1988891
TI  - Prognostic factors in stage IB squamous cervical cancer patients with low risk
      for recurrence.
AB  - About one-half of cervical cancer patients whose tumors recur after radical
      surgery have negative lymph nodes and clear resection margins. We evaluated 95
      patients with squamous cell tumors who underwent radical hysterectomy and pelvic
      lymphadenectomy between January 1975 and December 1985 and who were thought to be
      at low risk for recurrence to see whether other clinical or histopathologic
      factors were predictive of tumor recurrence. Detailed retrospective record review
      and complete pathology review were accomplished for each case. The 5-year
      actuarial survival rate was 89%. Nine patients developed recurrent disease
      (9.5%), of whom eight died. Several clinical features were evaluated as possible
      prognostic factors: patient age (P = .26), patient race (P = .60), cervical
      diameter (P = .24), extent of gross cervical involvement (P = .36), and presence
      of contact bleeding (P = .82). Histopathologic features were examined: depth of
      invasion (P = .31), number of mitoses (P = .42), character of the tumor-stromal
      border (P = .15), histologic differentiation (P = .02), lymph-vascular space
      invasion (P = .56), and width of tumor (P = .23). Depth of invasion did correlate
      with increasing tumor width (P less than .001). Once node- and margin-positive
      patients are excluded, differentiation may be the only feature useful in
      identifying patients at risk for recurrence. Because almost one-half of our
      patients had poorly differentiated tumors, sole use of this feature as a
      criterion for adjuvant therapy would have resulted in overtreatment of low-risk
      patients.

PMID- 1988892
TI  - Familial ovarian cancer in Israeli Jewish women.
AB  - Among 310 women with ovarian cancer of epithelial origin, eight ovarian cancer
      prone families were identified, accounting for 24 cases. Five first-degree
      relatives underwent prophylactic oophorectomy, and early ovarian carcinoma was
      diagnosed in one of them. Familial aggregation of ovarian cancer occurs in the
      Israeli Jewish population.

PMID- 1988893
TI  - Serial CA 125 levels during chemotherapy for metastatic or recurrent endometrial
      cancer.
AB  - The purpose of this study was to evaluate the role of serial CA 125 in monitoring
      disease status during chemotherapy in women with metastatic or recurrent
      endometrial cancer. CA 125 was measured in 21 women receiving cisplatin,
      etoposide, and Adriamycin for a total of 275 courses of chemotherapy (median
      eight). Eight of ten patients had elevated pre-therapy CA 125 levels (median 233
      U/mL). CA 125 became and/or remained negative in all 20 women with responding or
      stable disease and was elevated in all nine patients who relapsed. The median
      level at the time of relapse was 56 U/mL. Levels were elevated before clinical
      relapse in five of nine patients (56%). Serial CA 125 may aid in the management
      of women receiving chemotherapy for advanced or recurrent endometrial cancer.

PMID- 1988894
TI  - Bladder training in older women with urinary incontinence: relationship between
      outcome and changes in urodynamic observations.
AB  - The purpose of this study was to clarify the mechanism by which bladder training
      affects urinary incontinence. Urodynamic data and specific urodynamic diagnoses
      of 108 women with urinary incontinence were compared before and 6 months after
      treatment with bladder training. Before treatment, 76 women had sphincteric
      incompetence, 11 had detrusor instability, and 16 had both. After treatment, 33
      women no longer fulfilled the urodynamic diagnostic criteria for either sphincter
      or detrusor dysfunction. Controlling for severity before treatment, the number of
      incontinent episodes post-treatment was not associated with change in urodynamic
      diagnosis. Only the first sensation to void, voided volume, compliance,
      functional urethral length, and flow time showed any significant changes between
      pre- and post-treatment evaluations; however, none were correlated with change in
      the number of incontinent episodes. Bladder training does not appear to affect
      lower tract urodynamic variables or specific urodynamic diagnosis, and it is
      likely that its mechanism of action reflects adaptive behavioral changes.
      Physiologic changes not detected with techniques and/or criteria used in this
      study may still occur.

PMID- 1988896
TI  - Peritoneal closure or non-closure at cesarean.
AB  - The value of peritoneal closure at the time of cesarean birth was evaluated
      prospectively. Two hundred forty-eight women undergoing low transverse cesarean
      through a Pfannenstiel skin incision were assigned to one of two groups:
      peritoneum open (N = 127) or peritoneum closed (N = 121). The mean (+/- SEM)
      surgical time in the open group (48.1 +/- 1.2 minutes) was significantly less
      than for the closed group (53.2 +/- 1.4 minutes) (P less than .005). There were
      no postoperative differences between the groups in the incidence of wound
      infection, dehiscence, endometritis, ileus, and length of hospital stay. Our
      study suggests that leaving the parietal peritoneum unsutured is an acceptable
      way to manage patients at cesarean delivery.

PMID- 1988895
TI  - Upper genital tract isolates at delivery as predictors of post-cesarean
      infections among women receiving antibiotic prophylaxis.
AB  - The introduction of antibiotic prophylaxis for cesarean delivery has decreased
      the risk of postpartum endometritis and wound infection, but factors that
      contribute to prophylaxis failure are not understood. To determine factors that
      might contribute to postpartum infections following antibiotic prophylaxis, we
      cultured amniotic fluid, decidua, and chorioamniotic membrane specimens for
      anaerobic and facultative bacteria and for genital mycoplasmas at cesarean
      delivery. Women were assessed daily for the development of infections, and if
      endometritis developed, a protected endometrial culture was obtained. Postpartum
      endometritis developed in 16 and wound infection in four of 102 women. Infection
      rates were similar for women receiving cefotetan (N = 50) or cefoxitin (N = 52)
      for prophylaxis. The isolation of group B streptococcus (P less than .001) or
      Enterococcus faecalis (P = .03) from the upper genital tract at delivery was
      significantly associated with postpartum endometritis. Antibiotic-resistant
      organisms (other than enterococci) were recovered uncommonly at delivery or with
      postpartum infections. Group B streptococcus was susceptible to the prophylactic
      agents used, suggesting that virulence factors other than antibiotic resistance
      are important for the development of postpartum endometritis. Group B
      streptococcus, E faecalis, and bacteria associated with bacterial vaginosis were
      recovered from the endometrium at the time of postpartum endometritis.

PMID- 1988897
TI  - Mid-second-trimester labor induction: concentrated oxytocin compared with
      prostaglandin E2 vaginal suppositories.
AB  - A concentrated oxytocin infusion and prostaglandin E2 (PGE2) vaginal
      suppositories were compared in a retrospective analysis for indicated abortion in
      the mid-second trimester (17-24 weeks' gestation). Eighty-one women underwent
      second-trimester pregnancy termination, 59 by PGE2 suppositories and 22 by
      concentrated oxytocin infusion. Success was achieved by PGE2 in 93% (55 of 59)
      and oxytocin in 91% (20 of 22). The mean duration of labor was 13.1 hours with
      PGE2 and 8.2 hours with oxytocin. The mean dose of PGE2 was 65.2 mg; of oxytocin,
      200 units. Women who received PGE2 experienced nausea (46%), vomiting (37%),
      fever (64%), and diarrhea (20%) despite appropriate premedication. Few side
      effects occurred in the women who were treated with oxytocin. We conclude that
      concentrated oxytocin infusion seems to be a reasonable alternative to PGE2
      vaginal suppositories for induction of labor in the mid-second trimester.

PMID- 1988898
TI  - At the water's edge: where obstetrics and anesthesia meet.
AB  - Conflict exists between satisfying the parturient's desire for oral intake and
      traditional restrictive standards of obstetric and anesthesia departments.
      Surveys of institutions providing obstetric services reveal greatly varying oral
      intake policy. There is neither evidence of benefit in withholding fluids nor
      evidence of risk in allowing them. Prolonged fasting has potential liabilities.
      Maternal mortality is rare, and anesthesia-related causes are not among the
      common etiologies. Aspiration is not a significant factor in the modern era.
      Higher risk for anesthesia morbidity is associated with general anesthesia,
      particularly difficult intubation. Instead of implicating oral intake as a risk
      factor for pulmonary aspiration, the literature consistently emphasizes the
      critical role of properly trained and dedicated obstetric anesthesia personnel.
      Unless parturients are not candidates for regional anesthesia, a nonparticulate
      diet should be allowed. Liberal use of regional anesthesia as well as antacid
      prophylaxis is recommended.

PMID- 1988899
TI  - Estrogen replacement therapy: is previously treated cancer a contraindication?
AB  - The benefits of estrogen replacement therapy in preventing vasomotor symptoms,
      osteoporosis, and cardiovascular disease are well documented. Although estrogen
      is said to be contraindicated in patients successfully treated for endometrial
      and breast cancer, there are no data to substantiate this admonition. Experience
      suggests that it can be used safely in patients treated previously for
      endometrial cancer. Although there is little or no experience with estrogen use
      in the woman treated previously for breast cancer, circumstantial evidence
      suggests that it is not contraindicated in all such cases. Informed consent,
      patient desires, and risk-benefit considerations must enter into the decision to
      use estrogen in these patients.

PMID- 1988900
TI  - An international terminology of colposcopy: report of the Nomenclature Committee
      of the International Federation of Cervical Pathology and Colposcopy.

PMID- 1988901
TI  - Cone cerclage in pregnancy.
AB  - We report a technique of cone cerclage and the results and outcome in 17 patients
      who required a diagnostic cone biopsy in pregnancy. The mean age of the patients
      was 30.6 years (range 21-41). The mean gestational age was 18.8 weeks (range 10
      32) at the time of the procedure. There were no major complications and
      hemorrhage was not a significant problem. There were no second-trimester
      abortions. Two patients required beta-sympathomimetics to suppress uterine
      activity for longer than 24 hours after the procedure. Six patients had invasive
      carcinoma, nine had cervical intraepithelial neoplasia (CIN) III, and two had CIN
      II. In 14 cases, the endocervical and ectocervical margins were negative; two
      patients with CIN and one with multifocal microinvasion had positive margins.
      Cone cerclage is a safe and easy method for performing diagnostic cervical
      conization during pregnancy.

PMID- 1988902
TI  - Genetic diagnosis before the eighth gestational week.
AB  - Transabdominal chorionic villus sampling (CVS) by a freehand, ultrasound-guided
      technique was offered to 210 high-genetic-risk women at 6-7 weeks' gestation. It
      was carried out in 201 cases and postponed in nine cases (4.3%). Sampling was
      successful in 86 and 100% of cases after the first and the second needle
      insertions, respectively. Chorionic tissue specimens weighed at least 20 mg in
      86% of cases, and only 2% were below 10 mg. Early complications were present in
      7.9% of cases, apparently without any adverse effect on maternal or fetal
      outcome. The rate of fetal loss was 3.5%. Genetic diagnosis was concluded in 1-3
      days by rapid diagnostic methods. Although more extensive laboratory and clinical
      experience is necessary to evaluate adequately the safety of early transabdominal
      CVS, it may be advantageous to offer this technique to certain high-genetic-risk
      patients. The availability of genetic diagnosis before the eighth week makes
      clinical abortion by antiprogestins and prostaglandins a viable option in cases
      of affected embryos.

PMID- 1988903
TI  - Evaluation of two rapid group B streptococcal antigen tests in labor and delivery
      patients.
AB  - Two rapid group B streptococcal antigen tests were compared with nonselective
      blood agar culture in 1062 unselected patients admitted to labor and delivery.
      Vaginal specimens taken from each patient on admission were used to perform each
      of two rapid tests and corresponding cultures. The rapid tests were the Streptex
      latex agglutination assay and the Equate Strep B test, which uses a solid-phase
      immunoassay. Overall, 105 patients (9.9%) had at least one positive culture. The
      sensitivities for the rapid tests were 15.1% for Streptex and 21.5% for Equate.
      Specificities were 99.3 and 98.7%, respectively. Sensitivity was minimally
      increased in the setting of ruptured membranes for both tests. Likewise, use of
      separate swabs for streaking the culture plate and performing the rapid test
      increased the sensitivity, but this was not significant for either test. In
      control experiments, the limit of sensitivity of both rapid tests was 5 x 10(6)
      colony-forming units. We conclude that at present, these tests are not sensitive
      enough for routine use in this type of clinical setting.

PMID- 1988905
TI  - Quality assurance in obstetrics: a model.

PMID- 1988904
TI  - Attempted transcervical occlusion of the fallopian tube with the Nd:YAG laser.
AB  - A prospective multi-center trial was initiated to test the efficacy and safety of
      transcervical occlusion of the fallopian tube with the Nd:YAG laser. A multi
      center approach was deemed necessary because of the large sample size required to
      test adequately the effectiveness of sterilization procedures. However, efforts
      to continue the study as designed were abandoned because, of the 17 subjects
      completing the study, only four (24%) had bilateral tubal occlusion at the site
      of laser treatment. We conclude that the hysteroscopic method, as tested, is
      inadequate to provide permanent sterilization. Modification of the technique or
      alterations in patient preparation may improve the outcome.

PMID- 1988906
TI  - AIDS legislation passes House & Senate.

PMID- 1988907
TI  - Restructuring: specifics for home health.

PMID- 1988908
TI  - ANA issues position statement on support for confidential notification services
      and a limited "privilene to disclose".

PMID- 1988909
TI  - AIDS: what should we do?

PMID- 1988911
TI  - Coming to terms.

PMID- 1988910
TI  - Treating drug misuse helps in HIV.

PMID- 1988912
TI  - A new yardstick.

PMID- 1988913
TI  - The communication gap.

PMID- 1988914
TI  - Dual duty.

PMID- 1988915
TI  - Miscarriage. Too common a story?

PMID- 1988916
TI  - Miscarriage. Creating support.

PMID- 1988917
TI  - Miscarriage. Marking the loss.

PMID- 1988918
TI  - Collaborative auditing.

PMID- 1988919
TI  - Picture perfect. Interview by Harriet Gaze.

PMID- 1988920
TI  - Mental health. Mirror images.

PMID- 1988921
TI  - Mental health. Finding common ground.

PMID- 1988922
TI  - Killing time.

PMID- 1988924
TI  - Trauma training.

PMID- 1988923
TI  - Action on the environment. Clinical waste disposal in the community.

PMID- 1988925
TI  - An old familiar tale.

PMID- 1988926
TI  - Non-attendance at outpatient clinics.

PMID- 1988927
TI  - Ward sister as catalyst for individual care.

PMID- 1988929
TI  - Out on a limb.

PMID- 1988928
TI  - When do women decide to breastfeed?

PMID- 1988931
TI  - Diabetes. Wet, white and wild.

PMID- 1988930
TI  - Systems of life. The respiratory system. Part I.

PMID- 1988932
TI  - Diabetes. A new normality.

PMID- 1988933
TI  - An iron-carboxylate bond links the heme units of malaria pigment.
AB  - The intraerythrocytic malaria parasite uses hemoglobin as a major nutrient
      source. Digestion of hemoglobin releases heme, which the parasite converts into
      an insoluble microcrystalline material called hemozoin or malaria pigment. We
      have purified hemozoin from the human malaria organism Plasmodium falciparum and
      have used infrared spectroscopy, x-ray absorption spectroscopy, and chemical
      synthesis to determine its structure. The molecule consists of an unusual polymer
      of hemes linked between the central ferric ion of one heme and a carboxylate side
      group oxygen of another. The hemes are sequestered via this linkage into an
      insoluble product, providing a unique way for the malaria parasite to avoid the
      toxicity associated with soluble heme.

PMID- 1988934
TI  - Identification of a cDNA encoding a second putative prohormone convertase related
      to PC2 in AtT20 cells and islets of Langerhans.
AB  - PC2 and furin are two recently identified members of a class of mammalian
      proteins homologous to the yeast precursor processing protease kex2 and the
      bacterial subtillisins. We have used the polymerase chain reaction to identify
      and clone a cDNA (PC3) from the mouse AtT20 anterior pituitary cell line that
      represents an additional member of this growing family of mammalian proteases.
      PC3 encodes a 753-residue protein that begins with a signal peptide and contains
      a 292-residue domain closely related to the catalytic modules of PC2, furin, and
      kex2. Within this region 58%, 65%, and 50% of the amino acids of PC3 are
      identical to those of the aligned PC2, furin, and kex2 sequences, respectively,
      and the catalytically important Asp, His, and Ser residues are all conserved. On
      Northern blots, PC3 hybridizes to two transcripts of 3 and 5 kilobases. Tissue
      distribution studies indicate that both PC2 and PC3 are expressed in a variety of
      neuroendocrine tissues, including pancreatic islets and brain, but are not
      expressed in liver, kidney, skeletal muscle, and spleen. The high degree of
      similarity of PC3, PC2, and furin suggests that they are all members of a
      superfamily of mammalian proteases that are involved in the processing of
      prohormones and/or other protein precursors. In contrast to furin, PC3, like PC2,
      lacks a hydrophobic transmembrane anchor, but it has a potential C-terminal
      amphipathic helical segment similar to the putative membrane anchor of
      carboxypeptidase H. These and other differences suggest that these proteins carry
      out compartmentalized proteolysis within cells, such as processing within
      regulated versus constitutive secretory pathways.

PMID- 1988935
TI  - Pertactin, an Arg-Gly-Asp-containing Bordetella pertussis surface protein that
      promotes adherence of mammalian cells.
AB  - A 69-kDa protein has been identified on the surface of the Gram-negative pathogen
      Bordetella pertussis that can elicit a protective immune response in animal
      models. This protein is associated with virulent strains of B. pertussis but its
      function has remained unclear. In this report we demonstrate that purified
      preparations of the 69-kDa outer membrane protein can promote the attachment of
      Chinese hamster ovary (CHO) cells. The interaction between the mammalian cells
      and this protein can be specifically inhibited by an Arg-Gly-Asp (RGD)-containing
      synthetic peptide that is homologous with a region found in the 69-kDa protein
      sequence. These studies indicate that a specific cell binding site containing an
      Arg-Gly-Asp sequence may be involved in the interaction of this bacterial protein
      with mammalian cell surfaces. To further investigate the role of this protein as
      a bacterial adhesin, a mutant of B. pertussis W28 that does not express the 69
      kDa protein was constructed using the plasmid vector pRTP1. This mutant was 30
      40% less efficient at adhering to CHO cells and to human HeLa cells than was the
      parent strain. These data support a role for this 69-kDa outer membrane protein
      in the attachment of B. pertussis to mammalian cells. We propose the name
      "pertactin" for this protein.

PMID- 1988936
TI  - Queuine, a tRNA anticodon wobble base, maintains the proliferative and
      pluripotent potential of HL-60 cells in the presence of the differentiating agent
      6-thioguanine.
AB  - 6-Thioguanine (6-TG)-induced differentiation of hypoxanthine
      phosphoribosyltransferase (IMP: pyrophosphate phosphoribosyltransferase, EC
      2.4.2.8)-deficient HL-60 cells is characterized by 2 days of growth, after which
      morphological differentiation proceeds. Addition of the tRNA wobble base queuine,
      in the presence of 6-TG, maintains the proliferative capability of the cells. The
      ability of 6-TG to induce differentiation correlates with c-myc mRNA down
      regulation, but queuine has no effect on this parameter. Treatment with 6-TG for
      2-3 days commits HL-60 cells to granulocytic differentiation, and, once
      committed, these cells do not respond to the monocytic inducer phorbol 12
      myristate 13-acetate. Nonetheless, when cells are treated with queuine and 6-TG,
      they maintain the promyelocytic morphology and are capable of being induced down
      the monocytic pathway by phorbol 12-myristate 13-acetate as indicated by
      stabilization of c-fms mRNA and cell adherence. In the absence of queuine,
      phorbol 12-myristate 13-acetate is incapable of inducing monocytic markers in the
      6-TG-treated cells. The data presented indicate that 6-TG-induced differentiation
      of HL-60 cells is a tRNA-facilitated event and that the tRNA wobble base queuine
      is capable of maintaining both the proliferative and pluripotent potential of the
      cells.

PMID- 1988937
TI  - Action potential broadening and frequency-dependent facilitation of calcium
      signals in pituitary nerve terminals.
AB  - Hormone release from nerve terminals in the neurohypophysis is a sensitive
      function of action potential frequency. We have investigated the cellular
      mechanisms responsible for this frequency-dependent facilitation by combining
      patch clamp and fluorimetric Ca2+ measurements in single neurosecretory terminals
      in thin slices of the rat posterior pituitary. In these terminals both action
      potential-induced changes in the intracellular Ca2+ concentration ([Ca2+]i) and
      action potential duration were enhanced by high-frequency stimuli, all with a
      frequency dependence similar to that of hormone release. Furthermore, brief
      voltage clamp pulses inactivated a K+ current with a very similar frequency
      dependence. These results support a model for frequency-dependent facilitation in
      which the inactivation of a K+ current broadens action potentials, leading to an
      enhancement of [Ca2+]i signals. Further experiments tested for a causal
      relationship between action potential broadening and facilitation of [Ca2+]i
      changes. First, increasing the duration of depolarization, either by broadening
      action potentials with the K(+)-channel blocker tetraethylammonium or by applying
      longer depolarizing voltage clamp steps, increased [Ca2+]i changes. Second,
      eliminating frequency-dependent changes in duration, by voltage clamping the
      terminal with constant duration pulses, substantially reduced the frequency
      dependent enhancement of [Ca2+]i changes. These results indicate that action
      potential broadening contributes to frequency-dependent facilitation of [Ca2+]i
      changes. However, the small residual frequency dependence of [Ca2+]i changes seen
      with constant duration stimulation suggests that a second process, distinct from
      action potential broadening, also contributes to facilitation. These two
      frequency-dependent mechanisms may also contribute to activity-dependent
      plasticity in synaptic terminals.

PMID- 1988938
TI  - Conversion of 6-substituted tetrahydropterins to 7-isomers via phenylalanine
      hydroxylase-generated intermediates.
AB  - A new variant form of hyperphenylalaninemia has recently been discovered in which
      the patients characteristically excrete 7-biopterin in their urines in addition
      to the natural 6-biopterin (Curtius, H. Ch., Kuster, T., Matasovic, A., Blau, N.
      & Dhondt, J.-L. (1988) Biochem. Biophys. Res. Commun. 153, 715-721). This isomer
      had not been found previously in humans, and although its origin was not
      established, preliminary evidence suggested that it might be produced from 6
      biopterin. We have now found that 7-biopterin can be formed in vitro from (6R)
      tetrahydrobiopterin during the hydroxylation of phenylalanine catalyzed by
      phenylalanine hydroxylase [L-phenylalanine, tetrahydrobiopterin:oxygen
      oxidoreductase (4-hydroxylating), EC 1.14.16.1]. The resulting 7-biopterin was
      unequivocally identified by the following criteria: preparative isolation and
      conversion to 7-hydroxymethylpterin following periodate oxidation and borohydride
      reduction, quantitative conversion to pterin-7-carboxylic acid after oxidation
      with permanganate, and liquid chromatography/thermospray mass spectrometry.
      Addition of 4a-carbinolamine dehydratase, an enzyme involved in the regeneration
      of tetrahydrobiopterin from the pterin carbinolamine intermediate (also called 4a
      hydroxytetrahydrobiopterin) formed in the phenylalanine hydroxylase reaction,
      greatly decreased the amount of the 7-biopterin formed. This result implies that
      the in vitro formation of 7-biopterin occurs via the nonenzymatic rearrangement
      of the unstable substrate of the dehydratase, 4a-hydroxytetrahydrobiopterin, and
      suggests that this new variant of hyperphenylalaninemia may be caused by a lack
      of 4a-carbinolamine dehydratase activity. A mechanism for the rearrangement is
      proposed that predicts that other 6-substituted tetrahydropterin substrates of
      the aromatic amino acid hydroxylases could also give rise to rearranged products
      from an opening of the pyrazine ring of the corresponding 4a
      hydroxytetrahydropterin intermediate.

PMID- 1988940
TI  - Location of the active site for enzyme-adenylate formation in DNA ligases.
AB  - The enzyme-AMP reaction intermediate of the 102-kDa bovine DNA ligase I was
      digested with trypsin, and the adenylylated peptide was isolated by
      chromatography under conditions that maintain the acid-labile phosphoramidate
      bond. Microsequencing of the peptide showed that it contains an internal trypsin
      resistant lysine residue, as expected for the site of adenylylation. Inhibition
      of DNA ligase I activity by pyridoxal 5'-phosphate also indicated the presence of
      a reactive lysine residue in the catalytic domain of the enzyme. Comparison of
      the known primary structures of several other DNA ligases with the adenylylated
      region of mammalian DNA ligase I allows their active sites to be tentatively
      assigned by sequence homology. The ATP-dependent DNA ligases of mammalian cells,
      fission yeast, budding yeast, vaccinia virus, and bacteriophages T3, T4, and T7
      contain the active site motif Lys-Tyr/Ala-Asp-Gly-(Xaa)-Arg, with the reactive
      lysine residue flanked by hydrophobic amino acids. The distance between the
      postulated adenylylation site and the carboxyl terminus of the polypeptide is
      very similar in these ATP-dependent DNA ligases, whereas the size of the amino
      terminal region is highly variable.

PMID- 1988939
TI  - Structural differences between the hormone and antihormone estrogen receptor
      complexes bound to the hormone response element.
AB  - To investigate the molecular mechanism(s) by which the estrogen receptor (ER)
      modulates transcription, we compared the structures of receptor complexes
      containing estradiol, the agonist diethylstilbestrol, and the antagonist
      ICI164,384. The binding of ICI164,384 to nontransformed 8-9S ER does not preclude
      the salt-induced dissociation of the 90-kDa heat shock protein and releases the
      transformed homodimeric 5S ER as classically observed in the presence of agonist.
      We report that calf ER binds to the estrogen response element of the Xenopus
      vitellogenin A2 gene in either the absence or presence of hormone, agonist, or
      antagonist. These binding interactions were highly sequence- and receptor
      specific. These findings indicate that ligand binding in vitro is not absolutely
      required for dimerization or specific DNA binding of the ER. As demonstrated by
      gel retardation assays, the ICI164,384-ER complex bound to the response element
      displays a slower mobility than complexes formed in the presence of estradiol or
      agonist. This difference in electrophoretic mobility is suggestive of a
      conformational change in the complex induced by the ligand. An exchange
      experiment demonstrated that this alteration of the structure is reversible. We
      suggest that ICI164,384 induces conformational modifications within the ligand
      binding domain of the receptor that do not prevent binding to the response
      element but could fail to promote subsequent events required for gene
      transcription.

PMID- 1988942
TI  - Diets of yearling female primates (Papio cynocephalus) predict lifetime fitness.
AB  - The foraging of yearling baboons (Papio cynocephalus) was studied in Amboseli
      National Park, Kenya. The nutrient content of the diets of individual females was
      compared with the composition of energy-maximizing optimal diets. Energy in the
      diets of all individuals fell appreciably short of their respective optima.
      Nonetheless, linear combinations of just two variables, protein intakes in excess
      of requirements and proximity of energy intakes to those specified in the optimal
      diets, were sufficient to provide good predictions of reproductive lifespans,
      numbers of infants and juveniles produced, and probability of surviving to
      adulthood.

PMID- 1988941
TI  - Structure-function studies of human aromatase by site-directed mutagenesis:
      kinetic properties of mutants Pro-308----Phe, Tyr-361----Phe, Tyr-361----Leu, and
      Phe-406----Arg.
AB  - Aromatase, a cytochrome P450, catalyzes the formation of aromatic C-18 estrogenic
      steroids from C-19 androgens. Four mutants of human aromatase have been expressed
      in Chinese hamster ovary cells using a stable expression method. The activities
      of these mutants were determined using [1 beta,2 beta-3H]androstenedione, [19
      14C]androstenedione, and [1 beta,2 beta-3H]testosterone as substrates. The mutant
      Phe-406----Arg was completely inactive. Since there were only small changes in
      the Km and Vmax values for all substrates for mutants Tyr-361----Phe and Tyr-361-
      --Leu, the residue Tyr-361 appears not to be directly involved in the substrate
      binding. The mutant Pro-308----Phe had altered catalytic properties; the Km
      values for androstenedione, but not testosterone, decreased significantly. These
      results, along with those obtained from inhibition studies with aromatase
      inhibitors, 4-hydroxyandrostenedione and aminoglutethimide, suggest that Pro-308
      is probably situated in the active site of the enzyme and may be interacting with
      the D ring of the steroids.

PMID- 1988943
TI  - Solution conformations of the gamma-carboxyglutamic acid domain of bovine
      prothrombin fragment 1, residues 1-65.
AB  - Molecular dynamics simulations have been performed (AMBER version 3.1) on
      solvated residues 1-65 of bovine prothrombin fragment 1 (BF1) by using the 2.8-A
      resolution crystallographic coordinates as the starting conformation for
      understanding calcium ion-induced conformational changes that precede
      experimentally observable phospholipid binding. Simulations were performed on the
      non-metal-bound crystal structure, the form resulting from addition of eight
      calcium ions to the 1-65 region of the crystal structure, the form resulting from
      removal of calcium ions after 107 ps and continuing the simulation, and an
      isolated hexapeptide loop (residues 18-23). In all cases, the 100-ps time scale
      seemed adequate to sample an ensemble of solution conformers within a particular
      region of conformation space. The non-metal-containing BF1 did not unfold
      appreciably during a 106-ps simulation starting from the crystallographic
      geometry. The calcium ion-containing structure (Ca-BF1) underwent an interesting
      conformational reorganization during its evolution from the crystal structure:
      during the time course of a 107-ps simulation, Ca-BF1 experienced a trans----cis
      isomerization of the gamma-carboxyglutamic acid-21 (Gla-21)-Pro-22 peptide bond.
      Removal of the calcium ions from this structure followed by 114 ps of additional
      molecular dynamics showed significant unfolding relative to the final 20-ps
      average structure of the 107-ps simulation; however, the Gla-21-Pro-22 peptide
      bond remained cis. A 265-ps simulation on the termini-protected hexapeptide loop
      (Cys-18 to Cys-23) containing two calcium ions also did not undergo a trans---
      cis isomerization. It is believed that the necessary activation energy for the
      transitional event observed in the Ca-BF1 simulation was largely supplied by
      global conformational events with a possible assist from relief of intermolecular
      crystal packing forces. The presence of a Gla preceding Pro-22, the inclusion of
      Pro-22 in a highly strained loop structure, and the formation of two long-lived
      salt bridges prior to isomerization may all contribute to this finding.

PMID- 1988944
TI  - Complementary molecular shapes and additivity of the packing parameter of lipids.
AB  - Physical dimensions of a membrane component influence its phase preference upon
      hydration. A dimensionless packing parameter, S, given by S = V/al, where V is
      the hydrocarbon volume, a is the area of the head group, and l is the critical
      length of the hydrocarbon chain, is useful in determining the phase preference of
      a lipid, and the value of S usually lies between 0.5 and 1 for bilayers. Here,
      the value of S is calculated for phosphatidylcholine (PC) and
      lysophosphatidylcholine (lysoPC) as a function of chain length, and it is shown
      that diacylPC having an S value of less than 0.74 does not form bilayers. For
      example, diacylPC, up to a chain length of eight carbon atoms, forms only
      micelles, whereas higher homologs with S greater than 0.74 form bilayers. It is
      also shown that when lipid molecules having complementary shapes associate, the
      value of S becomes additive. Using the additivity of S, a number of experimental
      results for lipid mixtures can be explained. For example, lysoPC and cholesterol
      form lamellar structures between 45 and approximately 80 mol% cholesterol, and
      the additive value of S for this region is between 0.74 and 1. Similarly, the
      additivity of S shows that the maximum amount of cholesterol that can be
      incorporated into PC bilayers is 50 mol%, in agreement with experimental studies.

PMID- 1988945
TI  - Calmodulins with deletions in the central helix functionally replace the native
      protein in yeast cells.
AB  - Deletion of Glu-84, Glu-83 and Glu-84, or Ser-Glu-Glu-Glu (residues 81-84) from
      the central helix of mammalian calmodulin is known to result in a 5-7 times
      decrease in its apparent in vitro affinities for three calmodulin-dependent
      enzymes. However, based on in vitro experiments, it is difficult to estimate how
      these deletions might affect in vivo cellular function. The yeast Saccharomyces
      cerevisiae, which requires calmodulin for growth, provides an excellent system to
      evaluate these deletion proteins in vivo. Based on its ability to restore normal
      growth characteristics to yeast cells, mammalian calmodulin is functionally
      identical to the yeast protein; herein we evaluate the effect of deleting
      residues 84, 83 and 84, or 81-84 from the central helix. Sequences encoding the
      deletion proteins and an unaltered control sequence were introduced by means of a
      yeast shuttle vector and were expressed under control of the yeast calmodulin
      promoter. The deletion and control calmodulins are produced at levels similar to
      that observed for the yeast protein, and they completely restore normal growth
      characteristics. This result suggests that the regions deleted from the central
      helix are not critical for activation of any yeast calmodulin target normally
      required for cell growth or division. It is likely that there are twisting and
      shortening motions associated with the deletions from the central helix that
      alter significantly the spatial relationship between the two lobes of calmodulin.
      The abilities of the deletion calmodulins to restore completely normal growth
      characteristics to yeast cells suggest that the lobes of all the deletion
      proteins can still be appropriately positioned in calmodulin-target complexes.
      This is consistent with the hypothesis that the central helix of calmodulin is
      analogous to a flexible tether rather than to a rigid connector between the two
      lobes of the molecule.

PMID- 1988946
TI  - IRA2, an upstream negative regulator of RAS in yeast, is a RAS GTPase-activating
      protein.
AB  - The ras GTPase-activating protein (GAP), identified and characterized in
      mammalian cells, stimulates the intrinsic GTPase activity of ras proteins. We
      have previously proposed that the IRA genes, negative regulators of RAS genes in
      Saccharomyces cerevisiae, encode yeast homologs of the mammalian GAP. In this
      paper, we present the following evidence that a product of the IRA2 gene exhibits
      GAP activity similar to that of the mammalian GAP protein. (i) Extracts of yeast
      cells overexpressing IRA2 stimulated the GTPase activity of the yeast RAS2
      protein. (ii) An epitope for a monoclonal antibody (12CA5) was added to the N
      terminus of the IRA2 protein. The GAP activity of extracts prepared from cells
      expressing this fusion protein was shown to be immunoprecipitable by 12CA5. (iii)
      An IRA2 protein fused to glutathione S-transferase (GST) was produced and
      partially purified from Escherichia coli cells. GAP activity was detected with
      this purified GST-IRA2 fusion protein. (iv) The GAP activity of IRA2 proteins
      described above did not stimulate the GTPase activity of the RAS2Val19 protein, a
      protein having an amino acid alteration analogous to that found in mammalian
      oncogenic ras proteins. This result parallels studies showing that mammalian GAP
      is incapable of stimulating the GTPase activity of mammalian oncogenic proteins.
      The remarkable conservation between the GAP activity in mammalian and yeast cells
      supports the idea that the function of GAP is to negatively regulate ras proteins
      in mammalian cells.

PMID- 1988947
TI  - Heterologous introns can enhance expression of transgenes in mice.
AB  - In a previous study we showed that genomic constructs were expressed more
      efficiently in transgenic mice than constructs that were identical except for the
      lack of introns. Using the mouse metallothionein promoter-rat growth hormone gene
      construct as a model, we show that the first intron of the rat growth hormone
      gene is essential for high-level expression, whereas the other three introns are
      less effective. Several heterologous introns placed 3' of the coding region of an
      intronless rat growth hormone gene are also ineffective. However, insertion of
      some heterologous introns between the metallothionein promoter and the growth
      hormone gene improves expression. To determine whether addition of heterologous
      introns would provide a general strategy for improving expression, we have tested
      them in conjunction with other intronless genes and with different promoters.

PMID- 1988948
TI  - Substrate channeling in glycolysis: a phantom phenomenon.
AB  - It has been proposed that glycolytic enzymes form multienzyme complexes for
      direct transfer of metabolites from the producing enzyme to the utilizing one.
      Reexamination of the supporting evidence, which involves the transfer of NADH
      between its complexes with glycerol-3-phosphate dehydrogenase (alpha-glycerol
      phosphate dehydrogenase, GPDH; EC 1.1.1.8) and with L-lactate dehydrogenase (LDH;
      EC 1.1.1.27), has shown that the supporting evidence is based on
      misinterpretation of the kinetics of ligand exchange. Srivastava et al. have
      responded with a revision of their own and criticism of our data. To clarify this
      problem, we have carried out detailed kinetic studies on NADH binding to GPHD and
      LDH and on the displacement of enzyme-bound NADH by LDH or GPDH. The experiments
      were conducted at 10 degrees C in 50 mM Hepes, pH 7.5/100 mM KCl/1 mM EDTA/1 mM 2
      mercaptoethanol, using rabbit muscle GPDH and LDH. The results show that the
      kinetic patterns exhibited by the displacement of NADH-bound enzyme by either
      GPDH or LDH are consistent with a dissociative mechanism but not with a direct
      transfer mechanism. Theoretical analysis shows that a combined dissociative and
      direct transfer mechanism can explain the transient kinetic data reported by
      Srivastava et al. if, and only if, a majority (approximately 90%) of the enzyme
      present in lower concentration exists as a complex with the second enzyme.
      However, data from tracer and traditional sedimentation equilibrium and from gel
      filtration experiments show that LDH and GPDH do not form complexes in the
      presence of saturating NADH concentration when the enzyme concentrations are
      ranged between 4 and 50 microM, a concentration equal to or greater than that
      used by Srivastava et al. Our results demonstrate that GPDH and LDH do not form
      multienzyme complex and the transfer of NADH between these enzymes proceeds via a
      dissociative mechanism.

PMID- 1988949
TI  - Crystal structure of interleukin 8: symbiosis of NMR and crystallography.
AB  - The crystal structure of a host defense system chemotactic factor, interleukin 8,
      has been solved by molecular replacement using as a model the solution structure
      derived from nuclear magnetic resonance experiments. The structure was refined
      with 2 A x-ray data to an R factor of 0.187 (0.217 at 1.6 A). A comparison
      indicates some potential differences between the structure in solution and in the
      crystalline state. Our analysis also predicts that residues 4 through 9 on the
      amino terminus and the beta-bend, which includes His-33, may be important for
      receptor binding.

PMID- 1988950
TI  - Formation of DNA triplexes accounts for arrests of DNA synthesis at d(TC)n and
      d(GA)n tracts.
AB  - To study the mechanism of arrest of DNA synthesis at d(TC)n and d(GA)n sequences,
      single-stranded DNA molecules including d(TC)27 or d(TC)31 tracts or a d(GA)27
      tract were used as templates for in vitro assays of complementary DNA synthesis
      performed by extension of a primer with the Klenow polymerase or the Taq
      polymerase (Thermus aquaticus DNA polymerase). Electrophoresis of the products
      revealed that arrests occurred around the middle of these tracts. The arrests in
      the d(TC)n sequences were eliminated when dATP or dGTP was replaced with the
      analogue 7-deaza dATP or 7-deaza dGTP, respectively, or when the templates were
      preincubated with the Escherichia coli single-strand binding protein (SSB).
      Preincubation of the template including a d(GA)27 tract with SSB has also
      eliminated the arrests at this sequence. Furthermore, arrests did not occur at
      d[G(7-deaza A)]27 or d[(7-deaza G)A]27 tracts when molecules including such
      tracts were used as templates. These results are compatible with the notion that
      the arrests were caused by formation of d(TC)i.d(GA)i.d(TC)i and
      d(GA)i.d(GA)i.d(TC)i triplexes, in which the bases in the uncopied portions of
      the d(TC)n tracts, or of the d(GA)27 tract, and the purine bases in the newly
      synthesized d(TC)i.d(GA)i duplexes were bound by hydrogen bonds. In the assays
      performed with the Taq polymerase, the pH dependence (in the range of 6.0-9.0)
      and the temperature dependence of the arrests were determined. As the pH was
      lowered, the arrests in the d(TC)27 tract were enhanced, in line with the
      expected properties of d(TC)i.d(GA)i.d(TC)i triplexes. The arrests in the d(GA)27
      tract were enhanced by an increase in the pH. At pH 7.2 the arrests in the
      d(GA)27 tract persisted up to 80 degrees C, whereas the arrests in the d(TC)27
      tract were eliminated at 50 degrees C; these results presumably reflect the
      relative stabilities of the two triplexes mentioned above at this physiological
      pH value and could be biologically significant.

PMID- 1988952
TI  - Immunization of chimpanzees confers protection against challenge with human
      immunodeficiency virus.
AB  - Sustained high titers of neutralizing antibodies were elicited in three
      chimpanzees after sequential injections of different human immunodeficiency virus
      1 (HIV-1) antigen preparations derived from the HIV-1 BRU strain that included
      whole inactivated virus or purified recombinant proteins and then synthetic
      peptides identical to the major HIV-1 neutralizing epitope V3. The animals were
      challenged i.v. with 40 chimpanzee infectious doses (equivalent to 100 tissue
      culture 50% infectious doses) of a stock of HIV-1 IIIB isolate. After 6 mo of
      follow-up, all three animals appeared uninfected by serologic and virologic
      criteria, including polymerase chain reaction analysis and failure to isolate
      virus from peripheral blood lymphocytes, bone marrow, and lymph node tissue. Of
      two chimpanzees monitored for 1 yr, virus was isolated initially from one animal
      at 32 weeks, but the second chimpanzee was virus negative by all assays through
      12 mo; the third animal has remained virus negative through 9 mo of follow-up.
      These results indicate that it is possible to elicit protection against, or
      significantly delay infection of, HIV-1 by immunization, thus laying the
      foundation for development of an HIV-1 vaccine.

PMID- 1988951
TI  - Specific depletion of the B-cell population induced by aberrant expression of
      human interferon regulatory factor 1 gene in transgenic mice.
AB  - Interferons (IFNs) are well known both as antiviral proteins and as potent
      regulators of cell growth and differentiation. In fact, IFNs inhibit growth of
      various normal and transformed cell types. Previously, a nuclear factor, IRF-1
      (interferon regulatory factor 1), which binds to type I IFN and some IFN
      inducible gene promoters, was identified and cloned. Since the IRF-1 gene is both
      virus and IFN inducible, an intriguing issue is raised as to whether the IRF-1
      gene is functioning in IFN-mediated regulation of cell growth and
      differentiation. In this study, we generated transgenic mice carrying the human
      IRF-1 gene linked to the human immunoglobulin heavy-chain enhancer. In the
      transgenic mice, all the lymphoid tissues examined showed a dramatic reduction in
      the number of B lymphocytes (B cells). Preparation and analysis of bone marrow
      cells from the chimeric mice indicated that the bone marrow is the effective site
      for specific depletion of the B-cell population. In fact, transgenic bone marrow
      cells cocultured with a bone marrow-derived stromal cell line revealed an altered
      B-cell maturation pattern.

PMID- 1988953
TI  - X-ray scattering indicates that the leucine zipper is a coiled coil.
AB  - Dimerization of the bZIP class of eukaryotic transcriptional control proteins
      requires a sequence motif called the leucine zipper. We have grown two distinct
      crystal forms of a 33-amino acid peptide corresponding to the leucine zipper of
      the yeast transcriptional activator GCN4. This peptide is known to form a dimer
      of parallel helices in solution. X-ray scattering from both crystal forms shows
      reflections that are diagnostic of coiled coils. The most notable reflections
      occur at approximately 5.2 A resolution and correspond to the pitch of helices in
      coiled coils. There is no diffraction maximum near 5.4 A, the characteristic
      pitch of straight helices. Our results provide direct evidence that the leucine
      zipper of GCN4 is a coiled coil.

PMID- 1988954
TI  - Molecular dynamics simulation of the hydration shell of a B-DNA decamer reveals
      two main types of minor-groove hydration depending on groove width.
AB  - The conformation of the self-complementary B-DNA decamer C-C-A-A-C-G-T-T-G-G is
      known from a high-resolution x-ray crystal structure analysis. Molecular dynamics
      simulation of the hydration shell of the decamer has revealed two main types of
      minor-groove hydration, depending on groove width. The narrow part of the minor
      groove has a spine of hydration analogous to that described for the A + T-rich
      center of the minor groove in the dodecamer C-G-C-G-A-A-T-T-C-G-C-G [Drew, H. R.
      & Dickerson, R. E. (1981) J. Mol. Biol. 151, 535-556], the first hydration layer
      of which contains one water molecular per base pair. In contrast, in the wide
      part of the minor groove, each base is hydrated individually, water molecules
      lying predominantly in the base plane. In intermediate-width regions, preferred
      water-molecule sites are shifted away from the base plane in a 3'-to-5'
      direction. This shift becomes more pronounced as the minor groove narrows, until
      the two water molecules lie approximately midway between base pairs. If the minor
      groove is narrowed still further, it accommodates only one water molecule, and
      the hydration transforms to the well-known water spine. The observed pattern
      agrees with available crystallographic data and with our earlier calculations.
      The results confirm the assumption that preferred positions of water oxygens in
      the minor groove depend predominantly on groove width rather than on base
      sequence. However, the location of water hydrogens, and the network of hydrogen
      bonding, can depend on base sequence. We suggest a simple explanation of water
      spine formation in the narrow minor groove of a random DNA sequence. The spine of
      hydration may be a property of the minor groove of overwound variants of B-DNA,
      the C and D forms, for which the middle part of the decamer C-C-A-A-C-G-T-T-G-G
      can serve as a model.

PMID- 1988955
TI  - Overexpression of protein kinase C beta 1 enhances phospholipase D activity and
      diacylglycerol formation in phorbol ester-stimulated rat fibroblasts.
AB  - We are using a Rat-6 fibroblast cell line that stably overexpresses the beta 1
      isozyme of protein kinase C (PKC) to study regulation of phospholipid hydrolysis
      by PKC. Stimulation of control (R6-C1) or overexpressing (R6-PKC3) cells with
      phorbol ester results in an increase in diacylglycerol (DAG) mass with no
      increase in inositol phosphates, indicating that DAG is not formed by inositol
      phospholipid breakdown. A more dramatic DAG increase occurs in R6-PKC3 cells (4.0
      fold over basal) compared to R6-C1 cells (1.5-fold over basal). To further define
      the source of DAG, phosphatidylcholine (PC) pools were labeled with [3H]myristic
      acid or with [3H]- or [32P]alkyllyso-PC and formation of labeled
      phosphatidylethanol, an unambiguous marker of phospholipase D activation, was
      monitored. Phorbol ester-stimulated phosphatidylethanol formation is 5-fold
      greater in the R6-PKC3 cell line. Formation of radiolabeled phosphatidic acid
      (PA) is also enhanced by PKC overexpression. In cells double-labeled with [3H]-
      and [32P]-alkyl-lysoPC, the 3H/32P ratio of PA and PC are identical 15 min after
      stimulation, suggesting that a phospholipase D mechanism predominates. In support
      of this, the PA phosphohydrolase inhibitor propranolol decreased phorbol 12
      myristate 13-acetate-stimulated DAG formation by 72%. Increases in DAG and
      phosphatidylethanol were inhibited by the PKC inhibitors K252a and staurosporine.
      These results indicate that phospholipase D is regulated by the action of PKC.
      Enhanced phospholipase D activity may contribute to the growth abnormalities seen
      in PKC-overexpressing cells.

PMID- 1988956
TI  - Human growth hormone stimulates proliferation of human retinal microvascular
      endothelial cells in vitro.
AB  - Growth hormone (GH) has been implicated in the pathogenesis of proliferative
      diabetic retinopathy. We sought to determine whether this could be mediated by an
      effect of GH on proliferation of endothelial cells, and, for this purpose,
      established long-term cultures of human retinal microvascular endothelial cells
      (hREC) from normal postmortem human eyes. High-purity (greater than 95%) hREC
      preparations were selected for experiments, based on immunofluorescence with
      acetylated low density lipoprotein (LDL) and anti-factor VIII-related antigen.
      Growth requirements for these cells were complex, including serum for maintenance
      at slow growth rates and additional mitogens for more rapid proliferation.
      Exposure of hREC to physiologic doses of human GH (hGH) resulted in 100% greater
      cell number vs. control (P less than 0.01) but could be elicited only in the
      presence of serum. When differing serum conditions were compared, hGH stimulated
      [3H]thymidine incorporation up to 1.6- to 2.2-fold under each condition and
      increased DNA content significantly in the presence of human, horse, and fetal
      calf serum. Depending on the culture conditions used, the threshold hGH
      concentration for significant stimulation of hREC proliferation was 0.4-4
      micrograms/liter. In contrast, proliferation of human umbilical vein endothelial
      cells was not significantly altered by hGH added to concentrations as high as 200
      micrograms/liter. In summary, hREC respond to physiologic concentrations of hGH
      in vitro with enhanced proliferation. This specific effect of GH on retinal
      microvascular endothelial cells supports the hypothesis of a role for GH in
      endothelial cell biology.

PMID- 1988957
TI  - Water structure in cubic insulin crystals.
AB  - The electron density distribution of the solvent in the cubic insulin crystal
      structure, which occupies 65% of the volume, has been mapped from 1.7-A
      resolution diffraction data by an iterative difference Fourier method, using the
      previously determined protein structure as the refinement restraint. Starting
      with phases from the protein and a flat solvent model, the difference map
      calculated from the data was added outside the protein envelope, and the modified
      map was then used to recalculate phases for the iterative refinement. Tests of
      the method with model data, with the experimental data and a variant protein
      model, and by carrying out a partial refinement of the solvent map demonstrate
      that the refinement algorithm produces reliable values for the solvent density
      within the noise level of the data. Fluctuations in density are observed
      throughout the solvent space, demonstrating that nonrandom arrangements of the
      water molecules extend several layers from the well-ordered hydration shell in
      contact with the protein surface. Such ordering may account for the hydration
      force opposing close approach of hydrophilic surfaces and other long-range water
      dependent interactions in living structures.

PMID- 1988958
TI  - The Bradyrhizobium japonicum nolA gene and its involvement in the genotype
      specific nodulation of soybeans.
AB  - Several soybean genotypes have been identified which specifically exclude
      nodulation by members of Bradyrhizobium japonicum serocluster 123. We have
      identified and sequenced a DNA region from B. japonicum strain USDA 110 which is
      involved in genotype-specific nodulation of soybeans. This 2.3-kilobase region,
      cloned in pMJS12, allows B. japonicum serocluster 123 isolates to form nodules on
      plants of serogroup 123-restricting genotypes. The nodules, however, were
      ineffective for symbiotic nitrogen fixation. The nodulation-complementing region
      is located approximately 590 base pairs transcriptionally downstream from nodD2.
      The 5' end of pMJS12 contains a putative open reading frame (ORF) of 710 base
      pairs, termed nolA. Transposon Tn3-HoHo mutations only within the ORF abolished
      nodulation complementation. The N terminus of the predicted nolA gene product has
      strong similarity with the N terminus of MerR, the regulator of mercury
      resistance genes. Translational lacZ fusion experiments indicated that nolA was
      moderately induced by soybean seed extract and the isoflavone genistein.
      Restriction fragments that hybridize to pMJS12 were detected in genomic DNAs from
      both nodulation-restricted and -unrestricted strains.

PMID- 1988959
TI  - Heterogeneity of thymic epithelial cells in promoting T-lymphocyte
      differentiation in vivo.
AB  - To study in vivo the contribution of different thymic epithelial cells to T
      lymphocyte differentiation, we have established several nontransformed thymic
      epithelial cell lines and developed an in vivo assay, not involving exposure to
      drugs or radiation, that permitted us to study the capacity of these epithelial
      lines to support T-cell differentiation. We found that cell lines EA2 and ET,
      which express markers of cortical epithelial cells, produce interleukin 7 mRNA
      and after being injected into the spleens of young athymic nude mice support in
      vivo generation of CD4+CD8- T-cell receptor alpha beta+ T lymphocytes (ET line)
      or both CD4+CD8- and CD4-CD8+ T-cell receptor alpha beta+ T cells (EA2 line).
      Both cell lines also supported generation of T-cell receptor gamma delta+ T cells
      but appear not to support development of double-positive (CD4+CD8+) cells. One
      cell line, EB3, which expresses markers of medullary epithelial cells, produces
      interleukin 1 alpha RNA transcripts but does not support T-lymphocyte
      differentiation. The results provide direct evidence for functional heterogeneity
      of thymic epithelial cells in vivo and show the involvement of different cortical
      epithelial cells in the differentiation of T-cell progenitors into distinct
      thymocyte subsets.

PMID- 1988960
TI  - Immunoglobulins from animal models of motor neuron disease and from human
      amyotrophic lateral sclerosis patients passively transfer physiological
      abnormalities to the neuromuscular junction.
AB  - Amyotrophic lateral sclerosis (ALS) is a devastating human disease of upper and
      lower motoneurons of unknown etiology. In support of the potential role of
      autoimmunity in ALS, two immune-mediated animal models of motoneuron disease have
      been developed that resemble ALS with respect to the loss of motoneurons, the
      presence of IgG within motoneurons and at the neuromuscular junction, and with
      respect to altered physiology of the motor nerve terminal. To provide direct
      evidence for the primary role of humoral immunity, passive transfer with
      immunoglobulins from the two animal models and human ALS was carried out. Mice
      injected with serum or immunoglobulins from the animal disease models and human
      ALS but not controls demonstrated IgG in motoneurons and at the neuromuscular
      junction. The mice also demonstrated an increase in miniature end-plate potential
      (mepp) frequency, with normal amplitude and time course and normal resting
      membrane potential, indicating an increased resting quantal release of
      acetylcholine from the nerve terminal. The ability to transfer motoneuron
      dysfunction with serum immunoglobulins provides evidence for autoimmune
      mechanisms in the pathogenesis of both the animal models and human ALS.

PMID- 1988961
TI  - Transmural distribution of extracellular purines in isolated guinea pig heart.
AB  - The purine adenosine appears to be involved in regulation of coronary vascular
      tone. Little is known concerning the levels and distribution of adenosine and
      related purines in the extracellular fluid of the heart. We have measured
      epicardial and endocardial levels of adenosine, inosine, hypoxanthine, AMP, and
      IMP in isolated constant flow perfused guinea pig hearts by using a recently
      developed technique with porous nylon sampling discs. Venous effluent purine
      levels were also measured. Concentrations of all purines measured, excluding IMP,
      were significantly higher in endocardial fluid samples than in epicardial fluid
      samples (P less than 0.05). Conversely, IMP levels were significantly lower in
      endocardial than in epicardial samples. The magnitude of the
      endocardial/epicardial ratios for adenosine, inosine, hypoxanthine, AMP, and IMP
      were approximately 12:1, 4:1, 5:1, 4:1, and 1:2, respectively. To assess cellular
      damage, lactate dehydrogenase activity was measured in all fluid samples and was
      not significantly different in endocardial and epicardial fluid. These data
      support the existence of significant transmural gradients for extracellular
      purine levels in crystalloid perfused guinea pig hearts. Transmural differences
      in vasoactive adenosine levels may be partially due to the greater endocardial
      oxygen consumption and metabolism and may be involved in maintaining relatively
      high subendocardial blood flows in the face of high intramyocardial pressures.

PMID- 1988963
TI  - Hairpin formation within the enhancer region of the human enkephalin gene.
AB  - The 3',5'-cyclic adenosine monophosphate (cAMP)-inducible enhancer of the human
      enkephalin gene is located within an imperfect palindrome of 23 base pairs. We
      have found that a 23-base-pair oligonucleotide duplex containing the enhancer
      undergoes a reversible conformational transition from the duplex to two
      individual hairpin structures each formed from one strand of the duplex. Each
      individual hairpin forms with mismatched base pairs, one containing two GT pairs
      and the other containing two AC pairs. The conformational transition is
      stabilized by proton transfer to the hairpin containing AC mismatched pairs. The
      unique physical and thermodynamic properties of the enkephalin enhancer DNA
      suggest a model in which DNA secondary structure within the enhancer region plays
      an active role in cAMP-inducible activation of the human enkephalin gene via
      formation of cruciform structures.

PMID- 1988962
TI  - cDNA cloning, sequence analysis, and chromosomal localization of the gene for
      human carnitine palmitoyltransferase.
AB  - We have cloned and sequenced a cDNA encoding human liver carnitine
      palmitoyltransferase (CPTase; palmitoyl-CoA:L-carnitine O-palmitoyltransferase,
      EC 2.3.1.21), an inner mitochondrial membrane enzyme that plays a major role in
      the fatty acid oxidation pathway. Mixed oligonucleotide primers whose sequences
      were deduced from one tryptic peptide obtained from purified CPTase were used in
      a polymerase chain reaction, allowing the amplification of a 0.12-kilobase
      fragment of human genomic DNA encoding such a peptide. A 60-base-pair (bp)
      oligonucleotide synthesized on the basis of the sequence from this fragment was
      used for the screening of a cDNA library from human liver and hybridized to a
      cDNA insert of 2255 bp. This cDNA contains an open reading frame of 1974 bp that
      encodes a protein of 658 amino acid residues including 25 residues of an NH2
      terminal leader peptide. The assignment of this open reading frame to human liver
      CPTase is confirmed by matches to seven different amino acid sequences of tryptic
      peptides derived from pure human CPTase and by the 82.2% homology with the amino
      acid sequence of rat CPTase. The NH2-terminal region of CPTase contains a leucine
      proline motif that is shared by carnitine acetyl- and octanoyltransferases and by
      choline acetyltransferase. The gene encoding CPTase was assigned to human
      chromosome 1, region 1q12-1pter, by hybridization of CPTase cDNA with a DNA panel
      of 19 human-hamster somatic cell hybrids.

PMID- 1988964
TI  - Identification and characterization of "zinc-finger" domains by the polymerase
      chain reaction.
AB  - We have developed a method for amplifying DNA fragments containing tandem arrays
      of "zinc-finger" sequences of the transcription factor IIIA (Cys2-His2) type by
      using the polymerase chain reaction. Because these sequences occur as tandem
      arrays, a ladder of bands is produced upon amplification using primers derived
      from the amino- and carboxyl-terminal sequences of a zinc-finger domain. The
      "rungs" of this ladder correspond to DNA fragments encoding one zinc-finger
      domain, two adjacent zinc-finger domains, and so on. This is demonstrated by
      isolating individual bands corresponding to n zinc-finger domains and
      reamplifying them with the same primers. This yields a band of the original size
      as well as bands corresponding to 1 through (n - 1) zinc-finger domains. Direct
      evidence that these bands encode zinc-finger domains was obtained by cloning and
      sequencing a collection of the amplification products. Due to the lack of
      redundancy in the sequences obtained, we conclude that each band corresponds to a
      large number of unique zinc-finger-encoding sequences. The results from
      amplification reaction mixtures using genomic DNA from a variety of sources as
      template provide further evidence that zinc-finger domains occur widely and
      frequently in eukaryotic genomes. We believe that this method is a powerful
      technique for the isolation and characterization of zinc-finger-encoding genes.

PMID- 1988966
TI  - Applications of Markov random fields in medical imaging.

PMID- 1988967
TI  - An investigation of the 3D modulation transfer function used in 3D post
      reconstruction restoration filtering of SPECT imaging.

PMID- 1988965
TI  - Aminopeptidase A activity of the murine B-lymphocyte differentiation antigen BP
      1/6C3.
AB  - The predicted amino acid sequence of the cDNA encoding the murine B-lymphocyte
      differentiation antigen BP-1/6C3 suggested that it is a member of the zinc
      dependent metalloprotease family, possibly an aminopeptidase related to
      aminopeptidase N [microsomal aminopeptidase; alpha-aminoacyl-peptide hydrolase
      (microsomal), EC 3.4.11.2]. In the present studies, we examined the enzymatic
      activity of this antigen. From brush border preparations of the small intestine,
      a rich source of many endopeptidases and exopeptidases, the BP-1 antibody
      selectively removed aminopeptidase A [APA; L-alpha-aspartyl(L-alpha-glutamyl)
      peptide hydrolase, EC 3.4.11.7] activity. The APA activity of a panel of cell
      lines correlated in linear fashion with cell-surface levels of the BP-1/6C3
      antigen. APA activity was demonstrated for the BP-1/6C3 antigen immunopurified
      from the pre-B-cell membrane. This activity was enhanced by alkaline earth metals
      such as Ca2+ and was abrogated by amastatin and angiotensin, which are known
      competitive inhibitors of APA. The data indicate that the murine BP-1/6C3 antigen
      is active APA, an enzyme that catalyzes specifically the removal of
      unsubstituted, N-terminal glutamic acid and aspartic acid residues from peptides.

PMID- 1988968
TI  - Single photon emission computed tomography of the heart using cone beam geometry
      and noncircular detector rotation.

PMID- 1988969
TI  - Three-dimensional reconstruction for a multi-ring positron tomograph.

PMID- 1988970
TI  - Bayesian restoration of PET images using Gibbs priors.

PMID- 1988971
TI  - Optimization of scatter correction techniques using energy information: how many
      (photon) beans make five.

PMID- 1988972
TI  - Time-of-flight positron imaging algorithms.

PMID- 1988973
TI  - Parallelism in electrical impedance tomography.

PMID- 1988974
TI  - Video-rate reconstruction of CT and MR images.

PMID- 1988975
TI  - Null functions and eigenfunctions: tools for the analysis of imaging systems.

PMID- 1988977
TI  - A method for characterizing soft tissue microstructure using parametric
      ultrasound imaging.

PMID- 1988976
TI  - Four metrics for image variation.

PMID- 1988979
TI  - Common misconceptions about 3D FT MR imaging.

PMID- 1988978
TI  - Extraction of three-dimensional information from biplane images without prior
      knowledge of the relative geometry of the two views.

PMID- 1988980
TI  - Improved methods of low frequency restoration for dynamic range improvement in MR
      imaging.

PMID- 1988981
TI  - A spatial interaction model for statistical image processing.

PMID- 1988982
TI  - Synthetic MR images produced by subspace methods: a comparison.

PMID- 1988983
TI  - The MRI measurement of NMR and physiological parameters in tissue to study
      disease process.

PMID- 1988984
TI  - A new approach to dynamic study analysis.

PMID- 1988986
TI  - Evaluation of cytologic deformation by boundary-driven energy minimization.

PMID- 1988985
TI  - Matching of geometric models in the analysis of lumen shape in digital X-ray
      angiography.

PMID- 1988987
TI  - Early visual representation using regions defined by maximum gradient profiles
      between singular points.

PMID- 1988988
TI  - Application of a visual model to vascular segmentation.

PMID- 1988989
TI  - A hyperstack for the segmentation of 3D images.

PMID- 1988990
TI  - Structural and statistical object recognition in medical images.
AB  - Comparative results for LV identification are shown in Fig. 7, from which the
      following conclusions can be drawn: 1) success rate almost double when BOS are
      used. LV is finally found and correctly classified in 90% of cases, 2) a first
      class of error consists of undetected LVs. Since the process is aware of its
      failure, this is considered as a minor error. It happens with atypical images for
      which either the description is unadapted (4.7%) or some new BOSes (not
      encountered in the learning set) occur (2.7%). The latter case can be solved by
      updating the graph, contrarily to the first one, 3) a second class of error
      consists in misclassification. This is considered as a major error since the
      process is not aware of its failure. Such errors are due to either poor
      statistical classification (1.4%) or unmodelled BOSes (1.4%). The first case can
      be solved by improving the classification technique which is quite (too ?) simple
      in our work, while updating the graph should solve the second one.

PMID- 1988991
TI  - Definition and evaluation of a surface overlap criterion for medical image
      registration.

PMID- 1988992
TI  - Coherent image shape description via the intensity axis of symmetry.
AB  - Calculating the IAS for a grey-scale image has been accomplished by computing the
      SAs for each level curve in the image simultaneously using the active surface
      model and the image symmetry function. Linking quench mates on the active surface
      provides an effective method to partition an active surface into the individual
      axis sheets which comprise the IAS. Because the image regions associated with
      individual axis sheets often correspond to sensible image structures, the IAS can
      be used for shape-based image segmentation.

PMID- 1988994
TI  - 2D vs. 3D edge detection as a basis for volume quantitation in SPECT.

PMID- 1988993
TI  - Optimization of the constrained Algebraic Reconstruction Technique for the
      performance of a variety of visual tasks.
AB  - This work demonstrates the application of a method to optimize image
      reconstruction algorithms on the basis of the performance of specific visual
      tasks that are to be accomplished using the reconstructed images. The evaluation
      of task performance is numerically realized by a Monte Carlo simulation of the
      complete imaging chain, including the final inference based on the
      reconstructions. Fundamental to this evaluation is that it yields an average
      response by consideration of many initial scenes. It is shown that the use of the
      nonnegativity constraint in the Algebraic Reconstruction Technique can
      significantly improve performance in situations where there is a severe lack of
      measurements when the relaxation factor is optimized. There is no indication in
      any of the cases studied hitherto that the nonnegativity constraint can improve
      performance in situations where the data are complete, but noisy. It is also
      shown that neither the rms error nor the L1 error in constrained reconstructions
      are good predictors of task performance.

PMID- 1988995
TI  - Methods for improving the efficiency and versatility of volume rendering.

PMID- 1988996
TI  - Reinforcement of linear structure using parametrized relaxation labeling.
AB  - An approach for reinforcing underlying linear structure while suppressing
      unwanted noise, useful for analysis of medical images, has been presented. The
      method utilizes principles previously presented with regard to relaxation
      labeling processes, but differ in that the label set is now considered to be
      continuous and the distribution of label preference values for each object
      (pixel) parametrized by a single vector. Due to this parametrization, the total
      number of computations per pixel in the new method is now dependent only on the
      number of neighbors used in the computation, and not on the number of labels as
      well, as in previous methods. Thus, for a general reinforcement problem with m
      labels and n neighbors being considered for each pixel, the time complexity per
      object (pixel) per iteration goes as O (nm2) for the prototypical algorithm (e.g.
      (Zucker, et. al., 1977)) and is reduced by the approach presented here to O (n).
      The method uses a new approach for deciding local neighborhood influence and
      making a decision between reinforced linear structure with some magnitude and
      orientation and a no-structure condition based on the nonlinear (sigmoidal)
      thresholding of a linear vector sum. It should be noted that there is a
      similarity between this sigmoidal thresholding function and similar functions
      used in artificial neural networks (Hopfield, 1984). Ongoing work is being
      performed to further investigate such overlap. Also, it is planned to extend the
      approach in several ways. These include the ability to reinforce co-circularity,
      as well as to reinforce underlying planar structure by updating surface normals
      in true three-dimensional diagnostic imagery.

PMID- 1988997
TI  - Reversible 3D compression of CT data using HINT.

PMID- 1988998
TI  - Evaluation of a module for the fusion of data on blood vessels from multiple
      sources.

PMID- 1988999
TI  - The quantification of planar scintigraphy using three dimensional modelling of
      organ shadows.
AB  - A method to define biodistribution from planar scintigraphic data is presented.
      Sampling regions or regions of interest (ROI's) are first defined as the
      projection contour of organs. From anatomical knowledge the three dimensional
      volume of the organ whose shadow has been traced is reconstructed. When the
      relevant organ volumes including the whole body or relevant whole body part have
      been defined, the count rate density in each pixel is assumed to represent the
      sum of the product of the projecting organ partial volumes times the tracer
      concentrations in the underlying organs. The solution (the definition of organ
      concentrations) is found by a matrix inversion. Validation is obtained in two
      ways. The first method is illustrative: an image is reconstructed from the
      defined volumes modulated by the computed concentrations. This image, if the
      method is correct, should be a crisp equivalent of the original data and closely
      similar to it following blurring with a convolution kernel equal to the imaging
      system's point spread function. The second is analytical: from reconstructed
      S.P.E.C.T. data in which voxel values are directly proportional to organ
      concentrations, a planar image is reconstructed. Organ average voxel values are
      computed in the S.P.E.C.T. image with volumetric ROI's and in the reprojected
      planar image using the method described here. The methods should yield the same
      concentration data but for a scaling factor. The method has the advantage that it
      yields volumetric and concentration data which are directly applicable to MIRD
      type analysis. In effect, the standard man assumptions in MIRD analysis have been
      incorporated in the calculation of the concentrations.

PMID- 1989000
TI  - Measurement of left ventricular wall motion from contour shape deformation.
AB  - This paper has presented the formulation and initial results for a new algorithm
      aimed at estimating and quantifying the trajectories of points on the left
      ventricular wall of the heart based on two- dimensional image-derived shape
      information. The algorithm is based on first automatically estimating the LV
      contour for two frames and then sampling the contours and tracking the motion of
      each sample point. Work is currently in progress to evaluate and compare each of
      three shape-based matching criteria, and to extend the algorithm to multiple
      frames. Future work will extend the approach to three spatial dimensions,
      capitalizing on the idea that all of the basic concepts, including curvature
      measurement, can be readily adapted for the higher dimensional problem.

PMID- 1989001
TI  - Estimation of fractal dimension of parenchymal organs based on power spectral
      analysis of nuclear medicine scans.

PMID- 1989002
TI  - Implementation of iterative reconstruction in positron emission tomography.

PMID- 1989003
TI  - An analytical solution to the nonstationary reconstruction problem in single
      photon emission computed tomography.

PMID- 1989004
TI  - Stopping rules, Bayesian reconstructions and sieves.

PMID- 1989005
TI  - Development of non-symmetric two-dimensional filtering in Fourier transform
      space.

PMID- 1989006
TI  - Interrater reliability of therapists' judgements of graphed data.
AB  - Increased emphasis on the use of single-subject designs in physical therapy
      research suggests the need to examine whether therapists can meaningfully
      interpret the results of such research as part of the clinical decision-making
      process. With this goal in mind, the interrater reliability of therapists to make
      visual judgments from graphed data that included a trend line was examined.
      Thirty therapists were presented with 24 graphs of single-subject data from AB
      (baseline-treatment) designs. Each graph included a trend line calculated using
      the split-middle method of trend estimation. The trend line was computed using
      the baseline data and then extended into the treatment phase to "predict" patient
      performance. The analysis, using intraclass correlation coefficients (ICCs),
      revealed low interrater agreement, with ICC values ranging from .37 to .55 for
      the entire sample. Evidence is presented that the statistical backgrounds of some
      raters positively influenced interrater reliability. No statistically significant
      relationship was found between interrater agreement and visual components of the
      graphed data, such as changes in slope or variability.

PMID- 1989007
TI  - Methods of treating plantar ulcers.
AB  - The purpose of this article is to describe the indications, precautions, and
      fabrication techniques for orthotic devices the authors use to facilitate the
      healing of plantar ulcers. The methods of fabricating and applying three types of
      orthotic devices developed by the staff at the Gillis W Long Hansen's Disease
      Center--walking casts, walking splints, and cutout sandals--are described.
      Patient examples are given for each of the methods. These techniques, in
      conjunction with patient education and the use of special footwear, provide
      clinicians with procedures they can use to aid in the healing of plantar ulcers
      secondary to leprosy, diabetes, or other neuropathic conditions.

PMID- 1989008
TI  - Motor skill acquisition.
AB  - The purpose of this article is to provide a framework for understanding motor
      skill and the process by which it is acquired. A selective historical overview is
      presented to demonstrate how the study of movement is a necessary preliminary to
      the study of motor skill learning. The phenomenon of skill is explored as an
      inherent feature of goal-directed organisms whose effective functioning depends
      on achieving a degree of competence in solving problems that are encountered in
      the everyday world. The relationship between problems and solutions is discussed.
      Movement is examined as a problem-solving tool and as the means by which the
      individual expresses skill. Factors that influence the individual's level of
      skill are fully explored, along with the implications for functional behavior.
      The creative use of resources in problem solving is thoroughly examined, and
      tasks are discussed in terms of the demands imposed on the individual.

PMID- 1989009
TI  - Knowledge of results and motor learning--implications for physical therapy.
AB  - Relevant to this special series on movement science, a brief overview of research
      in the field of motor learning is provided. A distinction between learning and
      performance is emphasized with respect to experimental design and the evaluation
      of laboratory and clinical intervention techniques. Intrinsic and extrinsic
      feedback are defined. Basic principles of motor learning pertaining to the use of
      augmented feedback or knowledge of results (KR) are reviewed. Particular emphasis
      is placed on recent research regarding the effects of selected KR variations (KR
      relative frequency, bandwidth KR, and KR delay) on motor performance and learning
      in healthy young adults. Results are discussed in terms of short-lasting
      temporary performance effects and relatively long-lasting learning effects.
      Theoretical and practical implications from this research are discussed. It is
      suggested that it is appropriate to use the principles obtained through
      laboratory experimentation as guidelines rather than as exact recommendations
      when applying basic research findings to clinical practice.

PMID- 1989010
TI  - What is repeated in a repetition? Effects of practice conditions on motor skill
      acquisition.
AB  - The nature of repetition and its contribution to the acquisition of motor skills
      in neurologically healthy subjects are examined in this article. We argue that
      cognitive processing is a key component of practice, which is undermined by
      repetitive performances. The effects on motor learning of contextual
      interference, knowledge-of-results delivery schedules, and observation of models
      are examined, with particular reference to the nature of practice. The role of
      repetition in learning with respect to physical therapy is also discussed.

PMID- 1989011
TI  - A process-oriented model of human motor behavior: toward a theory-based
      rehabilitation approach.
AB  - The purpose of this article is to present a behavioral model of human motor acts
      that may have relevance for therapeutic procedures aimed at the restoration of
      motor function after neurological or orthopedic problems. A key point of this
      model is that motor behavior is the result of an integrated and adaptive
      biological system. Cognitive, perceptual, and motor mechanisms are not
      independent elements, but are viewed as inseparable parts of this functional
      system. Implications for therapy are discussed. [Mulder T. A process-oriented
      model of human motor behavior: toward a theory-based rehabilitation approach.

PMID- 1989012
TI  - Reliability of goniometric measurements and visual estimates of knee range of
      motion obtained in a clinical setting.
AB  - The purpose of this study was to examine the intratester and intertester
      reliability for goniometric measurements of knee flexion and extension passive
      range of motion (PROM). In addition, parallel-forms reliability for PROM
      measurements of the knee obtained by use of a goniometer and by visual estimation
      was examined. The intertester reliability for visual estimates of the PROM of the
      knee was also examined. Repeated measurements were obtained on 43 patients in a
      clinical setting. The intraclass correlation coefficients (ICCs) for intratester
      reliability of measurements obtained with a goniometer were .99 for flexion and
      .98 for extension. Intertester reliability for measurements obtained with a
      goniometer was .90 for flexion and .86 for extension. The ICCs for parallel-forms
      reliability for measurements obtained with a goniometer and by visual estimation
      ranged from .82 to .94. The intertester reliability for measurements obtained by
      visual estimation was .83 for flexion and .82 for extension. Results suggest
      clinicians should use a goniometer to take repeated PROM measurements of a
      patient's knee to minimize the error associated with these measurements.

PMID- 1989013
TI  - Reliability of measurements of cervical spine range of motion--comparison of
      three methods.
AB  - To determine reliabilities within and between persons measuring cervical active
      range of motion (AROM) three methods were examined: use of a cervical-range-of
      motion (CROM) instrument, use of a universal goniometer (UG), and visual
      estimation (VE). Measurements were made on 60 patients with orthopedic disorders
      of the cervical spine who were divided into three groups of 20 subjects each. All
      subjects were tested in a standardized seated position using operationally
      defined goniometric placements and nongoniometric estimation techniques. Cervical
      flexion and extension, lateral flexion, and rotation were measured. Intraclass
      correlation coefficients (ICCs) were used to quantify within-tester and between
      tester reliability. We found that goniometric measurements of AROM of the
      cervical spine made by the same physical therapist had ICCs greater than .80 when
      made with the CROM device or the UG. When different physical therapist measured
      the same patient's cervical AROM, the CROM device had ICCs greater than .80,
      whereas the UG and VE generally had ICCs less than .80.

PMID- 1989014
TI  - An experimental study on the effect of rigid fixation on the developing
      craniofacial skeleton.
AB  - Rigid fixation of the craniofacial skeleton has proven of great value in adult
      orthognathic and traumatic reconstructive surgical procedures. This technique has
      gained increased acceptance in the surgical treatment of infants and young
      children with congenital malformations, despite the fact that its effects on
      subsequent craniofacial growth are unknown. To examine this question, an
      experimental model using 25 young kittens was developed to compare rigid fixation
      with conventional wire fixation, with and without osteotomy. Our findings
      demonstrate a regional restriction of growth in the developing craniofacial
      skeleton when both wire and plate and screw fixation are utilized in concert with
      osteotomy. Further, a compensatory growth was observed in individual animals when
      plate fixation was utilized that was not seen in the wire-treated group. This
      suggests that there is a dynamic growth interaction between restriction and
      compensation in this setting.

PMID- 1989015
TI  - Treatment of exophthalmos.
AB  - Current procedures for Graves' exophthalmos fail to achieve complete correction.
      The standard orbital decompressions were therefore modified to maximize the
      degree of volumetric increase behind the axis of the globe. In 15 orbits, the
      preoperative exophthalmos averaged 9.5 mm, whereas the postoperative exophthalmos
      was 4.1 mm. Postoperative CT study demonstrated that the remaining posterior
      orbital wall, combined with the persistently increased intraocular muscle volume,
      blocked retrodisplacement of the globe, despite adequate total volumetric
      increase. The increased muscle volume varied from 2 to 5 cc. Despite this
      residual exophthalmos, the modified four-wall expansion provides excellent
      aesthetic results with visual improvement and resolution of chemosis and exposure
      keratitis.

PMID- 1989016
TI  - Nasal augmentation with split calvarial grafts in Orientals.
AB  - This study reports on my experience with autogenous split calvarial grafts in
      nasal augmentation in 62 Orientals. In 78 percent of patients, the procedure was
      performed under local anesthesia in an outpatient setting. Total operating time
      for harvesting of split calvarial grafts ranged from 20 to 55 minutes, with a
      mean of 32 minutes. Patients ranged in age from 16 to 48 years, with a mean of 27
      years. Follow-up was from 6 months to 8 years, with an average of 3.1 years.
      Intraoperative discomfort was uniformly low and well tolerated when local
      anesthesia was used. The complication rate was 8.0 percent, with three cases of
      minor seroma-hematoma formation at the bone-graft donor site. These were treated
      with aspiration. There were two recipient-site complications, with one case of
      complete bone resorption that occurred in a densely fibrotic nose with
      preexisting septal perforation and a case of overcorrection that was successfully
      rasped 1 year later. Because of their easy accessibility beneath the scalp, split
      calvarial grafts to the nose are useful in various types of nasal augmentation,
      and the technique is offered as a practical alternative to the use of alloplastic
      materials.

PMID- 1989017
TI  - A modified Goldman nasal tip procedure for the drooping nasal tip.
AB  - A modification of Irving Goldman's nasal tip procedure that borrows from the
      lateral crus to augment the height of the medial crus is described. Goldman's
      procedure has been modified by not including the vestibular skin with the segment
      of the lateral crus that is rolled medially to increase nasal tip projection, by
      adding a nasal septal cartilage strut between the medial crura for support when
      the medial crura are weak, and by maintaining a small separation caudally of the
      repositioned lateral crura at the new nasal dome to simulate a double nasal dome.
      This modified Goldman nasal tip procedure allows the surgeon to reshape the lower
      lateral nasal cartilage to increase nasal tip projection as an alternative to the
      use of a shield-type nasal tip graft, and at the same time it narrows the nasal
      tip with minimal resection of the lateral crus of the lower lateral nasal
      cartilage.

PMID- 1989018
TI  - Vascularized full-thickness parietal bone grafts in maxillofacial reconstruction:
      the role of the galea and superficial temporal vessels.
AB  - Reconstruction of bony structures of the face is always a problem as big as the
      defect and the function that must be replaced. Everything from simple grafts to
      sophisticated distant bone flaps has been used. Based on the studies of Cutting
      et al., Psillakis et al., and Casanova et al., we have developed the full
      thickness galeoparietal bone flap, initially for mandibular reconstruction, but
      of great use for all maxillofacial reconstructions. From July of 1987 to December
      of 1988, 14 patients have been operated on. The experience with this flap is
      shown in four patients as follows: primary reconstruction of a mandible as a
      result of ameloblastoma, secondary reconstruction of a mandible with associated
      old fractures and malalignment of segments, bilateral malar reconstruction in a
      patient with Treacher Collins syndrome, and severe sequelae of an already treated
      Romberg case. Small variations could be made to best accommodate the technique
      used to the defect we were treating. Some technical details, the experience, the
      results, and possible sequelae or complications are also discussed.

PMID- 1989019
TI  - Aesthetic augmentation of the posterior mandible.
AB  - The posterior mandible begins just behind the mental nerve and second bicuspid
      bilaterally, extends to the posterior edge of the ramus, and then runs superiorly
      to the zygomatic arch. Augmentation of the posterior mandible is possible by use
      of a synthetic implant that is tailored individually to each patient's specific
      needs. Implant plant thickness varies from 4 to 8 mm, with an average thickness
      of 6 mm. Careful preoperative planning is done based on an aesthetic assessment
      of the amount of highlighting desired, thickness of the soft tissues, and the use
      of life-size photographs and cephalometric and Panorex x-rays. A pattern is cut,
      and the implant is carved to fit the patient. Insertion of the material after
      careful tailoring to the individual patient's own mandibular size and
      configuration requires a generous posterior lower buccal sulcus incision.
      Antibiotic irrigation and systemic antibiotics are essential, and careful closure
      in two layers completes the procedure. One implant in the series extruded in a
      patient who had had radiation therapy, and one patient required repositioning of
      the implant. Otherwise, in 22 patients there were no infections or permanent
      morbidity. The procedure seems to be a realistic and safe one for both the
      youthful and aging face, as demonstrated in patients in this series, with ages
      varying from 16 to 40 years.

PMID- 1989020
TI  - Restoration of the anterior neck surface in the burned patient by free groin
      flap.
AB  - In treating extensive burn contractures of the anterior neck, we obtained good
      results using free flaps. Ninety-nine patients with neck contractures were
      treated with free flaps. The ages of the patients range from 2 to 64 years. We
      used 84 free groin flaps, 10 free latissimus dorsi musculocutaneous flaps, 2 free
      deltopectoral flaps, 2 free scapular flaps, and 1 free anterolateral thigh flap.
      In all patients, contractures were sufficiently released and no recurrences
      followed after a mean follow-up of 8.7 years. After defatting procedures, natural
      profiles and good appearances were restored, especially in patients in whom groin
      flaps were used.

PMID- 1989021
TI  - Botulinum A toxin for the treatment of adult-onset spasmodic torticollis.
AB  - Thirty-five patients with adult-onset idiopathic torticollis were treated by
      local injections of botulinum A toxin into dystonic cervical muscles. Substantial
      improvement with respect to reduction and elimination of pain was found in 81
      percent, improvement in posture deformity and involuntary spasms in 70 percent,
      increased range of motion of the neck in 78 percent, reduction in visible
      sternocleidomastoid hypertrophy in 86 percent, and improvement in tremor in 65
      percent. The syndrome was divided into four subtypes based on pattern of dystonic
      muscle groups involved in the dystonia, head and shoulder posture, and
      sternocleidomastoid muscle hypertrophy. Injection strategy based on this
      subdivision is described.

PMID- 1989022
TI  - Free vascularized thin corticoperiosteal graft.
AB  - This paper describes a new thin corticoperiosteal graft harvested from the medial
      condylar and supracondylar areas of the femur. It is based on the articular
      branch of the descending genicular artery and vein and consists of periosteum
      with a thin (0.5 to 1.0 mm) layer of outer cortical bone. By retaining the
      cortex, the cambium layer is preserved, and this is thought to have a better
      osteogenic capacity than vascularized periosteal grafts. This graft was used to
      treat six patients with fracture nonunion of the upper extremity in which
      conventional treatment had failed. Uneventful bony union was achieved in all
      patients within 10 weeks.

PMID- 1989023
TI  - Custom-made free vascularized compound toe transfer for traumatic dorsal loss of
      the thumb.
AB  - Dorsal compound traumatic thumb loss can be reconstructed in selected young and
      well-motivated patients with a custom-made partial great toe transfer. The
      transfer, including the nail complex and vascularized piece of bone, can be
      fashioned by longitudinally cutting the distal phalanx to approach the appearance
      of the opposite thumb and to allow for more normal nail appearance. Ten patients
      illustrate this technique and emphasize its reconstructive potential as well as
      cosmetic acceptance.

PMID- 1989024
TI  - Vascularized bone allografts: in vitro assessment of cell-mediated and humoral
      responses.
AB  - The immunologic consequences of transplantation of vascularized bone allografts
      have not been previously characterized. In this study, knee allografts, both
      vascularized and nonvascularized, were transplanted from Lewis rats to Brown
      Norway rats across a strong histocompatibility barrier. A total of 66 transplants
      and 8 control animals were evaluated. The vascularized knee grafts consisted of 1
      cm of proximal tibia and distal femur with a minimal muscular cuff isolated on
      the femoral vessels, and these were transplanted to a heterotopic, subcutaneous
      position on the abdominal wall of the recipient rat. Nonvascularized allografts
      (identical but without anastomoses) were transplanted for comparison. The cell
      mediated response was measured by lymphocytotoxicity assay, and the humoral
      response was measured by cytotoxic antibody assay, both employing 51Cr-labeled
      target cells. The timing and intensity of the immune response differed according
      to the type of graft. The vascularized bone allografts generated significant cell
      mediated and humoral responses as early as 5 days posttransplant. A significant
      humoral response in nonvascularized bone allografts was not apparent until day
      14, while cell-mediated response in these grafts was variable. These findings
      were correlated with the histologic appearance of the grafted tissue.
      Cyclosporine, which was administered to one group of vascularized bone
      allografts, resulted in the suppression of both types of immune responses. The
      histologic appearance of this group resembled that of isografts transplanted as
      controls. The clinical application of vascularized bone allografts may offer
      significant advantages over nonvascularized allografts in the reconstruction of
      massive bone defects. Complications such as nonunion, fracture, and collapse of
      articular segments seen in nonvascularized allograft transplantation may be
      avoided by preservation of the blood supply to the graft. Characterization of the
      immune response to vascularized bone allografts may subsequently allow the
      manipulation of the host and/or graft tissue and promote graft incorporation.

PMID- 1989026
TI  - Expanding the limits of composite grafting: a case report of successful nose
      replantation assisted by hyperbaric oxygen therapy.
AB  - A successful nose replantation assisted by hyperbaric oxygen therapy is
      presented, with a brief discussion of the possible mechanisms and a brief
      literature review of the use of hyperbaric oxygen in tissue preservation and
      replantation. Although it is not certain that the hyperbaric oxygenation ensured
      the survival of the replanted nose in this 2-year-old girl, there was documented
      change in graft appearance during the initial hyperbaric oxygen treatment. A 1
      month, 1-year, and 2-year follow-up is included.

PMID- 1989025
TI  - Arteriovenous shunting and regional blood flow in myocutaneous island flaps: an
      experimental study in pigs.
AB  - In eight pigs, total blood flow, regional capillary blood flow distribution, and
      arteriovenous (AV) shunting were studied during the first 4 postoperative hours
      after elevation of a myocutaneous rectus abdominis island flap. Capillary blood
      flow and AV shunting were measured using radioactive microspheres before flap
      creation and 1 and 4 hours after surgery. Total blood flow, measured continuously
      as venous outflow, increased in the first postoperative hour (p less than 0.05).
      Elevation of the flap caused a slight decrease in skin capillary blood flow (p
      less than 0.05), whereas muscular capillary blood flow increased (p less than
      0.01). AV shunting accounted for 50 percent of the total flap blood flow, whereas
      it was negligible in the abdominal wall prior to flap elevation. Thus stalk blood
      flow, skin appearance, and skin temperature may be poor indicators of nutritional
      capillary perfusion. However, the clinical and nutritional consequences of these
      findings remain to be established.

PMID- 1989027
TI  - Metastatic melanoma to the facial nerve.
AB  - Isolated metastatic malignant melanoma to the facial nerve has never been
      reported. This presentation illustrates a primary melanoma of the helix of the
      ear that was treated by excisional biopsy and then wedge resection in 1983. The
      primary melanoma was Clark's level IV and 1.3 mm in thickness. In 1985, a facial
      paresis slowly developed. There was no gross evidence of recurrent melanoma in
      the ear or neck, but CT scan showed a mass in the region of the stylo mastoid
      foramen. A reoperation of the primary site revealed metastatic melanoma in the
      facial nerve, expanding it to approximately 10 times its normal size. A composite
      resection was done for the melanoma, and the paralyzed face was immediately
      rehabilitated by a masseter muscle transfer. The patient received 6000 rads to
      this area postoperatively and has remained free of disease to date, having
      returned to his profession as a dentist. A detailed study of all the specimens
      indicated that this represented a primary metastasis to the facial nerve.

PMID- 1989028
TI  - Simultaneous bilateral forearm revascularization.
AB  - A successful simultaneous bilateral forearm revascularization was performed on a
      17-year-old boy. Functional recovery of both forearms was evaluated 42 months
      after injury. The patient can use both hands for the activities of daily living.
      So far, he has been employed and has no significant psychological problems.
      Temporary intraluminal silicone shunts are extremely helpful for reducing
      ischemic damage to the injured limb. The sufficient skeletal shortening of the
      upper limb replantation is crucially important. The wounds must be managed by
      aggressive and repeated debridement. Accurate primary nerve repair is essential,
      and the early postoperative rehabilitation is also important to achieve a
      satisfactory functional return. The functional replanted or revascularized upper
      extremity is superior to an amputation or prosthesis, especially in the cases of
      bilateral upper extremity amputation or devascularization.

PMID- 1989029
TI  - Trigger finger secondary to anomalous lumbrical insertion: a case report and
      review of the literature.
AB  - Trigger finger is a relatively common clinical entity, most frequently caused by
      stenosing tenosynovitis. Several other conditions not related to tenosynovitis
      also have been described as a cause of triggering, and these have been reviewed.
      We present a rare anomaly of the fourth lumbrical muscle insertion as a cause of
      triggering of the right little finger. This was completely relieved following
      excision of the anomalous muscle. This rare anatomic variant should be added to
      the list of potential causes of trigger finger.

PMID- 1989030
TI  - Diphallia and hindgut duplication.
AB  - Diphallia is a rare congenital condition that presents in many, varied ways.
      Associated anomalies are to be expected. These anomalies should be sought out and
      treated as early in the patient's life as possible because they are the principal
      cause of mortality in these individuals. Half the patients reviewed by Ravitch in
      1953 with duplication of the colon and genital tracts died of intestinal
      complications. Definitive genital repair should be done at an age where the
      anatomy is of large enough caliber for eased surgical manipulation, but prior to
      the age of recall. From our experience with hypospadias repair, the optimal age
      seems to be 12 months of age. Each case must be treated individually in order to
      achieve the best functional and aesthetic result.

PMID- 1989031
TI  - A new mandibulotomy technique for the dentate patient.
AB  - Past mandibulotomy techniques, useful for surgical access to pathology of the
      head and neck, are complicated by postoperative malocclusion when performed on
      dentate patients. Malocclusion results from closure of the gap created by the saw
      blade during reconstruction. A new method of mandibulotomy bicortically splits
      the symphysis using an osteotome, with modifications to spare healthy dentition.
      The bicortical split osteotomy allows the hemimandibular segments to be
      approximated, accurately aligned, and rigidly fixed with three bone screws and a
      dental arch bar.

PMID- 1989032
TI  - Aerodynamic assessment of speech using the PERCI-PC: evaluation and reliability.

PMID- 1989034
TI  - Posttraumatic orbitozygomatic deformities.

PMID- 1989033
TI  - Reflex sympathetic dystrophy syndrome: consensus report of an ad hoc committee of
      the American Association for Hand Surgery on the definition of reflex sympathetic
      dystrophy syndrome.
AB  - This report proposes that reflex sympathetic dystrophy be defined as a pain
      syndrome in which the pain is accompanied by loss of function and evidence of
      autonomic dysfunction. In the clinical setting, this diagnosis is usually
      associated with other anatomic and psychological diagnoses and may be associated
      with a variety of systemic illnesses and medicolegal factors. All components
      should be assessed before a treatment plan is established. Priorities should go
      to emergency care, acute injuries, and systemic illness, psychiatric problems,
      and chronic anatomic problems, in that order. Early, accurate diagnosis improves
      prognosis.

PMID- 1989035
TI  - Ten commandments for safe lipoplasty.

PMID- 1989037
TI  - The concentric mastopexy and the purse-string suture.

PMID- 1989036
TI  - A new suction-assisted device for removing glandular gynecomastia.

PMID- 1989038
TI  - Dysplastic nevi.

PMID- 1989039
TI  - Pathology training for residents in plastic surgery.

PMID- 1989041
TI  - Our responsibility for impaired colleagues.

PMID- 1989040
TI  - Levator veli palatini muscle eustachian tube function.

PMID- 1989042
TI  - Putting research into practice.
AB  - Two nursing units at the James A. Haley Veterans' Hospital in Tampa, FL, used a
      model directed toward translating research outcomes into clinical knowledge for
      use in a practice setting. Each unit developed its own unique subjects, based on
      problem identification by the nursing staff. The clinical areas followed
      different courses, and the results varied. Many differences between the two units
      became apparent, such as mode of delivery of nursing care (primary versus team
      nursing) and differences in staffing patterns. These differences had an impact on
      successful implementation of the model. This article describes the Conduct and
      Utilization of Research in Nursing (CURN) model as a process that guides nursing
      staff in integrating research and clinical practice.

PMID- 1989043
TI  - Intermittent catheterization: sterile or clean?
AB  - Bacteriuria--asymptomatic and symptomatic--always has the potential to develop
      into a serious problem when intermittent catheterization is being used. Research
      on the best method of reducing bacteriuria is inconclusive. Studies have focused
      on the use of sterile technique, oral or vesical antibiotics, and the frequency
      of catheterization. This article presents a summary of current research on
      bacteriuria in the patient requiring intermittent catheterization.

PMID- 1989044
TI  - Case management in head injury rehabilitation.

PMID- 1989045
TI  - Recognizing poststroke depression.
AB  - Depression following stroke is a complication that frequently is untreated. Lack
      of awareness of those at risk for poststroke depression, combined with lack of
      information about depression in stroke patients, may be one reason for this
      neglect. This article reviews recent studies on characteristics of poststroke
      depression. The location of the lesion, degree of functional loss, and
      distinction between major and dysthymic (minor) depression all are factors that
      influence poststroke depression.

PMID- 1989046
TI  - An analysis of rehabilitation nurses' time allocation.

PMID- 1989047
TI  - Using Neuman's model to analyze a clinical situation.

PMID- 1989048
TI  - The workforce of the future: contradicting the doomsayers.

PMID- 1989049
TI  - Schema validation criticized.

PMID- 1989051
TI  - Addressing sexuality in the elderly.
AB  - Many social myths and stigmas surround sexuality in the elderly and may account
      for society's and the medical profession's often ignoring sexuality in these
      older citizens. Rehabilitation nurses who deal with clients of any age with
      altered sexual needs should be especially sensitive to the fact that sexual
      assessment and counseling are very important elements in the rehabilitation
      process for the promotion of optimum functioning.

PMID- 1989050
TI  - Pressure sore prevention education with the spinal cord injured.
AB  - The purpose of this qualitative single case study was to explore and describe the
      various formal and informal pressure sore prevention (PSP) educational encounters
      that occurred with an adolescent spinal cord injured client during his initial
      admission in an inpatient rehabilitation facility. Data collection supported the
      conclusion that nurses engaged most frequently in educational encounters with the
      client. Based on study findings, nurses should consider the following in planning
      client teaching: (a) assessing a client's learning style on admission and
      considering this when choosing teaching methods; (b) timing the delivery of PSP
      education to coincide with times when the information and skills would be most
      immediately applicable and relevant for the client; and (c) clarifying PSP
      measures of highest priority with clients while educating them. It also is
      suggested that rehabilitation nurses consider striking a balance between modeling
      important PSP measures in earlier phases of a rehabilitation program and
      encouraging client independence in these behaviors in later program phases.

PMID- 1989052
TI  - Making the ED waiting game a little easier to play.

PMID- 1989053
TI  - Diabetes: what to teach parents and child.

PMID- 1989054
TI  - Would you recognize this toxic emergency?

PMID- 1989055
TI  - Hypertension. First-line drug therapy.

PMID- 1989056
TI  - We've organized our approach to pressure sores.

PMID- 1989057
TI  - Why can't your patient hear you?

PMID- 1989058
TI  - A non-specialist's guide to the CCU.

PMID- 1989059
TI  - Starting life with HIV.

PMID- 1989060
TI  - Nursing the mind. Assessing your patient's diet.

PMID- 1989062
TI  - How fluid deprivation affects the terminally ill.

PMID- 1989061
TI  - After Cruzan: The right to die.

PMID- 1989063
TI  - Brain tumor: what it feels like living with one.

PMID- 1989064
TI  - When you suspect a child was burned intentionally.

PMID- 1989065
TI  - Nurse completes special ed team at U.S. DOE.

PMID- 1989066
TI  - Reflections of an expert witness.

PMID- 1989067
TI  - Nurse featured in Women's Day assignment.

PMID- 1989068
TI  - MRC funding: no freeze.

PMID- 1989069
TI  - Women and AIDS.

PMID- 1989070
TI  - The raging bull of Berkeley.

PMID- 1989071
TI  - Conflict over release of clinical research data.

PMID- 1989072
TI  - Looking for the father of us all.

PMID- 1989073
TI  - Mitogenesis is only one factor in carcinogenesis.

PMID- 1989074
TI  - Visualizing the higher order folding of a catalytic RNA molecule.
AB  - The higher order folding process of the catalytic RNA derived from the self
      splicing intron of Tetrahymena thermophila was monitored with the use of Fe(II)
      EDTA-induced free radical chemistry. The overall tertiary structure of the RNA
      molecule forms cooperatively with the uptake of at least three magnesium ions.
      Local folding transitions display different metal ion dependencies, suggesting
      that the RNA tertiary structure assembles through a specific folding intermediate
      before the catalytic core is formed. Enzymatic activity, assayed with an RNA
      substrate that is complementary to the catalytic RNA active site, coincides with
      the cooperative structural transition. The higher order RNA foldings produced by
      Mg(II), Ca(II), and Sr(II) are similar; however, only the Mg(II)-stabilized RNA
      is catalytically active. Thus, these results directly demonstrate that divalent
      metal ions participate in general folding of the ribozyme tertiary structure, and
      further indicate a more specific involvement of Mg(II) in catalysis.

PMID- 1989075
TI  - Participation of the TATA factor in transcription of the yeast U6 gene by RNA
      polymerase C.
AB  - Fractionation of transcription extracts has led to the identification of multiple
      transcription factors specific for each form of nuclear RNA polymerase. Accurate
      transcription in vitro of the yeast U6 RNA gene by RNA polymerase C requires at
      least two factors. One of them was physically and functionally indistinguishable
      from transcription factor IID (TFIID or BTF1), a pivotal component of polymerase
      B transcription complexes, which binds to the TATA element. Purified yeast TFIID
      (yIID) or bacterial extracts that contained recombinant yIID were equally
      competent to direct specific transcription of the U6 gene by RNA polymerase C.
      The results suggest the formation of a hybrid transcription machinery, which may
      imply an evolutionary relation between class B and class C transcription factors.

PMID- 1989077
TI  - A kinetic partitioning model of selective binding of nonnative proteins by the
      bacterial chaperone SecB.
AB  - An in vitro assay for the interaction of SecB, a molecular chaperone from
      Escherichia coli, with polypeptide ligands was established based on the ability
      of SecB to block the refolding of denatured maltose-binding protein. Competition
      experiments show that SecB binds selectively to nonnative proteins with high
      affinity and without specificity for a particular sequence of amino acids. It is
      proposed that selectivity in binding is due to a kinetic partitioning of
      polypeptides between folding and association with SecB.

PMID- 1989078
TI  - Systemic lupus erythematosus in a black South African child. First documented
      case report.
AB  - Systemic lupus erythematosus (SLE) is poorly described among black children in
      Africa despite being more frequent among some black adult populations than their
      white counterparts. The first black South African child with SLE is documented.
      The patient was a 10-year-old girl who had fever, facial rash (with complement
      (C4) deposited at the dermo-epidermal junction of normal skin), weight loss,
      central nervous system involvement (depression, withdrawal, retinal exudates),
      renal involvement (glomerular filtration rate 54 ml/min/1.73 m2; membranous
      nephropathy with mild mesangial proliferation; World Health Organisation
      classification Vb), alopecia, lymphadenopathy, hepatomegaly, positive Coombs
      test, hypeocomplementaemia, anti-DNA antibodies and positive anti-nuclear factor.

PMID- 1989076
TI  - T cell receptor peptide therapy triggers autoregulation of experimental
      encephalomyelitis.
AB  - Encephalitogenic T cells specific for myelin basic protein share common V beta 8
      peptide sequences in their T cell receptor (TCR) that can induce autoregulatory T
      cells and antibodies that prevent clinical signs of experimental autoimmune
      encephalomyelitis (EAE). It is not known, however, if TCR peptides can treat
      established disease. To test its therapeutic value, TCR-V beta 8-39-59 peptide
      was injected into rats with clinical signs of EAE. This treatment reduced disease
      severity and speeded recovery, apparently by boosting anti-V beta 8 T cells and
      antibodies raised naturally in response to encephalitogenic V beta 8+ T cells.
      These results demonstrate that synthetic TCR peptides can be used
      therapeutically, and implicate the TCR-V beta 8-39-59 sequence as a natural
      idiotope involved in EAE recovery. Similarly, human TCR peptides may be effective
      in enhancing natural regulation of autoreactive T cells that share common V
      genes.

PMID- 1989079
TI  - Primary Sjogren's syndrome associated with inappropriate antidiuretic hormone
      secretion. A case report.
AB  - A patient in whom primary Sjogren's syndrome and inappropriate antidiuretic
      hormone secretion were associated is reported. This is the first report of such
      an association. The possible pathophysiological mechanisms are discussed and
      vasculitis proposed as the underlying pathogenetic mechanism.

PMID- 1989080
TI  - Complexions fretting about fast foods.

PMID- 1989081
TI  - Familial hypercholesterolaemia in a black patient--completing the picture.

PMID- 1989082
TI  - A case of fever and haemolysis mimicking malaria.

PMID- 1989084
TI  - Escherichia coli septicaemia and meningitis complicating a septic incomplete
      abortion.

PMID- 1989083
TI  - Computed tomography appearances of sagittal sinus thrombosis in a neonate.

PMID- 1989085
TI  - Trauma--today and tomorrow.

PMID- 1989086
TI  - Neutron therapy--clinical considerations.

PMID- 1989087
TI  - Don Craib's legacy.

PMID- 1989088
TI  - Prognostic factors affecting the survival of patients with multiple myeloma. A
      retrospective analysis of 86 patients.
AB  - A retrospective analysis of data concerning 86 patients with multiple myeloma was
      carried out in order to evaluate factors affecting survival. The overall median
      survival was 621 days. In a univariate analysis the following factors were
      significantly associated with poor survival: serum creatinine greater than or
      equal to 150 mmol/l, haemoglobin less than 11 g/dl and serum calcium values
      greater than 2.75 mmol/l; and Eastern Cooperative Oncology Group performance
      status 3-4. However, age, sex, Durie and Salmon staging, lytic lesions, serum
      immunoglobulin concentration, urine Bence Jones protein, percentage of plasma
      cells in the bone marrow, proteinuria, and type of chemotherapy given were not
      significantly associated with survival. A strong prediction of survival was found
      by grouping the serum creatinine and haemoglobin levels of patients at
      presentation.

PMID- 1989089
TI  - Gastric carcinoma in Durban's Indian population.
AB  - Histologically proven gastric carcinoma was studied to establish the incidence
      and pattern of the disease in the Indian population of Durban. The incidence in
      this population was found to be low, 6.9/100,000/year. Over a 7-year period (1980
      1986) 115 patients were treated for gastric carcinoma at R. K. Khan Hospital.
      There was a male preponderance, and the average age at presentation was 56 years.
      The commonest presenting symptoms were dyspepsia and vomiting, and the majority
      of patients presented with advanced disease. Only a third underwent resection, a
      third had no treatment, and a third underwent palliative bypass or laparotomy
      only. The majority of patients who had a palliative bypass or no treatment died
      within 9 months. The 5-year survival rate for patients undergoing curative
      resection was 38% and for palliative resection 9%. To improve survival, emphasis
      must be on early diagnosis and it is recommended that any patient with dyspepsia
      who is over the age of 30 years should have an endoscopic investigation.

PMID- 1989090
TI  - The practical significance of lactose maldigestion in institutionalised black
      children.
AB  - A study was carried out to determine the practical significance of a high
      prevalence of lactose maldigestion in institutionalised children whose diet
      included 500 ml milk daily. Thirty of 34 children at a child welfare home were
      found to be lactose maldigesters as judged by a 2-hour rise in breath hydrogen of
      20 parts per million or more after an oral load of lactose. Breath hydrogen tests
      were also performed on the same group of children, before and up to 150 minutes
      after the routine mid-morning cup of milk. Sixteen of the 30 lactose-maldigesting
      children did not show increased breath hydrogen up to 2.5 hours after milk. No
      children were clinically intolerant of either the lactose or the milk. In these
      children the degree of lactose digestion was much improved in the non-fasting
      state when measured by the breath hydrogen response to milk lactose. Lactose
      maldigestion per se is not a contraindication to institutional feeding routines,
      including regular moderate milk intake.

PMID- 1989091
TI  - Prolonged after-effects of pneumonia in children.
AB  - Sixty-two black children were prospectively followed up for 1-7 years after
      pneumonia contracted at a median age of 17 months. In 55% of cases the pneumonia
      was measles-associated and 27% had serological evidence of infection with other
      respiratory viruses. Recurrence of cough or wheeze for more than 6 months
      occurred in 85% with just over 50% having recovered during the follow-up period.
      While the highest incidence of persistent symptoms occurred in children after
      measles superinfected with another virus, this was not significant. Abnormal
      radiographic features persisted in 53% of children and consisted of peribronchial
      and/or parenchymal lesions. Abnormal large and small airway calibre and/or
      bronchial hyperreactivity were found in one-third of children, and were
      significantly more common in those children whose main symptom was recurrent
      wheezing. Clinical and lung function abnormalities years after lower respiratory
      tract infection in this group of disadvantaged children compare with reports from
      more privileged groups. Recognition that long-term sequelae occur may prevent
      inappropriate subsequent management of symptomatic children.

PMID- 1989092
TI  - Clinical characteristics of childhood asthma.
AB  - A prospective study was undertaken of 298 asthmatic children attending a
      paediatric allergy clinic in Bloemfontein. A detailed history was obtained, and
      skin tests were performed. Male predominance and an early age of onset were
      confirmed. Symptomatic allergic rhinitis was an extremely common finding. A
      family history of allergy was obtained in over 90% of cases. Respiratory tract
      infections, changes in the weather and exercise were found to be the most common
      asthma-inducing factors. Common allergens were grass pollen (63%) and animal
      danders. House-dust mite (25%) and dietary allergens (less than 20%) were
      relatively uncommon. The failure to recognise the symptoms of asthma in children,
      particularly young children, was identified as an ongoing problem.

PMID- 1989093
TI  - Clinical significance of aero-allergen identification in the western Cape.
AB  - Positive identification and documentation of the seasonal variation of aero
      allergens and the immune responses to them has important implications for the
      timing of allergen avoidance measures and the selection of patients suitable for
      immunotherapy. The relative abundance of aero-allergens in the Cape Peninsula
      during 1984-1987 was measured by continuous volumetric air sampling, using a
      Burkard spore trap. Mould spore counts of greater than 3,000 spores/m3 were found
      throughout the year and were only exceeded by pollen grains in the months of
      September and October (range 4,800-7,400 spores/m3). Gramineae and Compositae
      spores were found perennially in significant numbers. Pollen from allergenic
      trees peaked at fixed times each year: oak in August; plane in September and pine
      between August and October. Grasses found on the Peninsula include sweet vernal,
      Bermuda grass, rye grass, common reed, Johnson grass, brome grass, canary grass,
      annual meadow and kikuyu. In vivo skin tests in 209 children with known allergic
      disease were positive to Dermatophygoides pteronyssimus (73%), South African
      grasses (38%), tree pollens (22.4%), flower and weed pollens (19.6%), cat (27%),
      dog (12%) and feathers (18.6%). One-third of the 1,372 children screened at Red
      Cross War Memorial Children's Hospital Allergy Service had positive specific IgE
      responses to environmental allergens. Investigation of 62 children possibly
      allergic to grass using the radio-allergosorbent test revealed positive results
      in 25 (41%). Of these, 92% were positive to Timothy grass, a grass not occurring
      in the Cape Peninsula. Knowledge of cross-reactivity profiles for local allergens
      minimises the number of tests required in allergy diagnosis.

PMID- 1989094
TI  - Incidence of atmospheric pollen in the Pretoria-Witwatersrand-Vereeniging region
      during 1987/1988.
AB  - Atmospheric pollen and spores have been monitored continuously in the Pretoria
      Witwatersrand-Vereeniging region (PWV) since 1987. Two Burkard 7-day recording
      traps were used in Johannesburg and Pretoria, and 11 gravity samplers were
      installed at various sites in the PWV. An analysis of the pollen component and
      pollen calendars average data for 1987 and 1988 are presented. Grass pollen was
      the most significant contributor in absolute and relative terms, comprising 52%
      of total pollen. The season peaked between October and March, but grass pollen
      was found throughout the year. Pollen of Northern Hemisphere trees was abundant,
      relative to that of indigenous trees. The flowering season for these exotics was
      very short and intense, possibly due to the short spring season. Seasonal taxa
      started flowering earlier in Pretoria than in Johannesburg. Herbaceous taxa were
      well represented in the atmospheric sample. The major contributor was the daisy
      family. The greatest proportion of pollen, 58.8%, was non-seasonal. Species in
      this category flower consecutively throughout the year. Of the taxa, 28.4% were
      spring-flowering. The allergenicity of pollen encountered in the atmospheric
      sample is discussed.

PMID- 1989095
TI  - Thrombotic side-effects of lower limb venography. The use of heparin-saline
      flush.
AB  - In a prospective study of 256 postoperative patients, bilateral lower limb
      venography was performed using meglumine iothalamate followed by heparin-saline
      flushing of the deep veins, and the complications of the procedure were assessed.
      No patient developed clinical evidence of deep-vein thrombosis after the
      venogram. In 117 patients fibrinogen uptake was performed 24 hours after the
      venogram. A new positive area on the uptake scan developed in 3 patients (2.6%).
      Local swelling or haematoma at the injection site occurred in 15 patients (5.9%),
      cellulitis in 2 (0.8%) and minor contrast reactions in 6 (2.3%). There were no
      major reactions and no procedure-related mortality. The reasons for the wide
      variation in the reported incidence of post-venogram thrombosis are considered
      and the importance of heparin-saline flushing of the deep veins to prevent this
      complication is discussed.

PMID- 1989096
TI  - Ear and hearing disorders in rural grade 2 (Sub B) schoolchildren in the western
      Cape.
AB  - Four hundred and one children living in rural areas with a high level of poverty
      were assessed for ear and hearing disorders in their second year of schooling.
      Overall, only 40.3% of these children had both normal-appearing ear drums and
      normal hearing thresholds bilaterally; 14% had obstructing wax plugs; 17% had
      evidence of past acute otitis media with scarring or progression to chronicity-
      6% having perforations; 31% had middle-ear effusions and/or their sequelae; and
      33% had some impairment of hearing but, if the effect of testing in the classroom
      environment is considered, there was probably only significant impairment in 9%.
      It is suggested that the prevalence of chronic ear disorders is a useful marker
      of the quality of primary care in rural communities.

PMID- 1989097
TI  - Trauma--the malignant epidemic.
AB  - Trauma is the commonest cause of death in children and young adults in the USA
      and the UK and the incidence of both accidental and non-accidental injury
      continues to increase. In the Western world more pre-retirement years of life are
      lost annually from trauma than malignant disease, heart disease, and AIDS
      combined, and by the beginning of the last decade injury deaths outnumbered
      deaths from all other causes combined in those under 35 years of age. In South
      Africa, although infectious diseases continue to exact their toll, a similar
      pattern is emerging. Alcohol and speed are responsible for the majority of motor
      vehicle accidents, while the increasing ownership of firearms directly parallels
      the homicide rates from these weapons. Stricter application of the legislation
      governing alcohol, driving and firearm control is required and a regionalised
      trauma care programme is desperately needed to contain this epidemic.

PMID- 1989098
TI  - The 'present state' examination and the structured clinical interview in Zulu.
AB  - The language, cultural and reality factors found to be important in the Zulu
      translation of the 'present state' examination (PSE) and the structured clinical
      interview for the Diagnostic and Statistical Manual of Mental Disorders (SCID)
      are discussed and compared with a previous translation of the PSE in Xhosa. The
      psychopathological items of the PSE and SCID apply to Zulu-speaking patients and
      the instruments are valid in this setting.

PMID- 1989099
TI  - The referral letter--a problem of communication.
AB  - This cross-sectional descriptive study assesses the letters sent with referred
      patients to Red Cross War Memorial Children's Hospital, Cape Town, and makes
      appropriate recommendations. During the 6-month period 1 July-31 December 1987,
      9,288 letters were photocopied at the admissions offices of the hospital. A
      sample of the letters collected, systematically stratified to represent the
      available days during the study, was analyzed. Detailed analysis of 1,143 (12.3%)
      letters was undertaken. The private sector, i.e. general practitioners, was the
      largest referral agency, followed by community-based day hospitals. The quality
      of information in referral letters was comparable to that found in other studies.
      The quality of letters influenced the writing of replies by hospital staff. There
      is a need to develop ways of improving communication between hospital staff and
      referral agents.

PMID- 1989100
TI  - Reoperative abdominal surgery.

PMID- 1989101
TI  - Reoperation for biliary strictures.
AB  - Benign bile duct strictures most often follow intraoperative injury not
      recognized until later. The ideal reconstruction entails a mucosa-to-mucosa
      anastomosis without tension, usually with a stent tube to maintain patency in the
      immediate postoperative period. The mortality rate for reoperation and bile duct
      reconstruction in patients who are not cirrhotic is approximately 2%, and success
      rates average 85%. Prevention of operative injuries by the use of
      cholangiography, careful dissection, and removal of the gallbladder from the
      fundus downward is the best treatment.

PMID- 1989102
TI  - Variceal rebleeding after portosystemic shunting. Strategies and solutions to a
      vexing problem.
AB  - The purpose of this review was to discuss an approach to the treatment of
      recurrent bleeding from esophageal or gastric varices after portosystemic shunt.
      From our own clinical experience, as well as that of others, it appears that re
      establishment of portal decompression should offer the best chance at long-term
      survival. Luckily, innovations in angiographic technique have allowed attainment
      of this goal without the inordinate risk of an operative procedure. However, not
      all patients' situations will be amenable to such treatment. For some of them,
      operative decompression of the portal venous system can be carried out in an
      anatomic area previously untouched. For those patients in whom no decompression
      is possible, direct endoscopic treatment of the varices will offer an
      alternative, albeit temporizing, approach.

PMID- 1989103
TI  - Repeat operation for failure of antireflux procedures.
AB  - The majority of patients who receive modern antireflux operations obtain
      substantial long-term relief of their symptoms. About 10% to 15% will have
      persistent or recurrent problems, some severe enough to warrant reoperation for
      correction. With careful symptom review, barium study, endoscopy, and manometry,
      the mechanism of failure becomes evident, and remedial surgical treatment may
      proceed. The results at reoperation are not as good as those of the primary
      procedure, which emphasizes the need for proper diagnosis and choice of procedure
      and for reliable execution of technique at the initial treatment.

PMID- 1989104
TI  - Reoperation for small intestinal obstruction.
AB  - Today, intestinal adhesions represent the most frequent etiology for complete or
      partial intestinal obstruction. Although partial obstruction can be treated
      nonoperatively with a considerable likelihood of success, intestinal
      strangulation cannot uniformly be predicted or prevented. Complete intestinal
      obstruction is associated with a significant incidence of strangulation if not
      treated by a vigorous surgical approach. Consequently, complete intestinal
      obstruction secondary to adhesions is still a surgical disease. Attempts at
      control of the adhesion process include mechanical methods to prevent subsequent
      obstruction and chemical methods to prevent the adhesion process itself. The
      invasive mechanical methods appear dated. A variety of agents have been used
      either systemically or in the peritoneal cavity to prevent the establishment of
      intra-abdominal adhesions. Agents that do not contribute to subsequent morbidity
      or impede the native host defense mechanisms should be utilized. High-molecular
      weight dextran and nonsteroidal anti-inflammatory agents show some promise of
      being both safe and effective. As is frequently the case, the bottom line in
      preventing and treating intra-abdominal adhesions is appropriate surgical
      technique. Intestinal adhesions can be related clearly to leaving damaged,
      devitalized, or ischemic tissue in the peritoneal cavity or to excessive
      roughness in handling of tissues. Steps such as avoidance of excessive suture
      material and unnecessary handling of the bowel will do much to prevent subsequent
      adhesion generation. Likewise, the surgical lysis of intraperitoneal adhesions is
      frequently fraught with complications such as intra-abdominal abscess or
      postoperative incisional failure. This is again related to surgical technique and
      most directly to the use of blunt dissection to divide adhesions. Knife
      dissection in the lysis of adhesions is recommended. This technique, combined
      with excellent intraoperative hemostasis, can be associated with a marked
      diminution in the incidence of postoperative fistulas and abscesses.

PMID- 1989105
TI  - Reoperative versus conservative management for gastrointestinal fistulas.
AB  - Development of a fistula is a serious complication. It is necessary to identify
      its anatomic and pathologic features, as these can influence the outcome of
      treatment independent of the primary disease. Electrolyte abnormalities should be
      addressed as volume deficits are being restored. Sepsis, the most common cause of
      death in patients with fistulas, must be controlled, and the skin must be
      protected. Reoperation and conservative management are not opposing forms of
      therapy but rather are complementary.

PMID- 1989106
TI  - Reoperation for intra-abdominal abscess.
AB  - Reoperative procedures for patients with abscess and other septic complications
      remain among the most difficult management problems in general surgery. The
      diagnosis of intra-abdominal septic complications has been greatly enhanced
      within the last 10 years but remains imperfect and requires clinical judgment
      that transcends objective methods. Surgical drainage remains the mainstay of care
      for patients with postoperative intraabdominal abscess.

PMID- 1989107
TI  - Revision and closure of the colostomy.
AB  - Reoperative stomal surgery includes the correction of complications and closure
      of a colostomy. Necrosis, retraction, and stenosis are the most frequently
      occurring complications and are simply corrected by straightforward techniques.
      Prolapse of the colostomy and parastomal hernia occur less frequently. Their
      repair is slightly more complex than that of the previous group of complications.
      Colostomy closure ranges from simple suture closure of the loop colostomy,
      through anastomosis of the divided colostomy, to the sometimes difficult
      gastrointestinal reconstruction after the Hartmann procedure. Death after closure
      of colostomy is infrequent, but anastomotic complications occur after all types
      of closure. Leak and sepsis are by far the most frequent anastomotic
      complications. Stenosis occurs less often. The same degree of care exercised
      during colectomy and anastomosis is necessary for optimal results after colostomy
      closure.

PMID- 1989108
TI  - Alkaline reflux gastritis.
AB  - Alkaline reflux gastritis and the symptoms associated with alkaline reflux
      gastritis have been reported in the medical literature since shortly after
      Billroth successfully performed his first gastrectomy in the 1880s. The disease
      process is produced by, or at least is associated with, the reflux of alkaline
      secretions into the gastric remnant. Although it occurs after any procedure that
      ablates the pylorus including pyloroplasty, it would appear to be most common
      after a Billroth II gastrojejunostomy. How the alkaline secretions cause the
      gastritis is still controversial. Clearly, the most effective therapy is to
      reroute the secretions from the biliary tract, pancreas, and duodenum so that
      they will not reflux into the gastric remnant. This is most effectively
      accomplished by a Roux-en-Y gastrojejunostomy with the afferent limb measuring at
      least 18 inches (40 cm). The surgeon and the patient should be aware that the
      construction of such a gastric outlet channel is associated with delayed gastric
      emptying. The etiology of this impaired emptying is also controversial. If the
      patient has symptoms of dumping (either early or late), these symptoms may also
      be abated using the Roux limb. At least 40% of patients will have gastric outlet
      obstruction. Supportive therapy is appropriate in the majority of these patients.

PMID- 1989109
TI  - Reoperation for failed gastric bypass procedures for obesity.
AB  - Reoperation is worthwhile when there is an obvious defect in the gastric
      reduction operation that has failed to control weight. Reoperation occasionally
      is necessary to correct a complication of gastric bypass. Vertical banded
      gastroplasty is the operation of choice for reoperations, as it provides weight
      control while eliminating the problems of bypass. Conversion of a horizontal to a
      vertical pouch is safe but requires careful attention to the technique to avoid
      injury to the other organs in the area and preservation of blood supply to the
      stomach. The gastrogastrostomy across the old horizontal staple line in the
      vertical pouch can be constructed in a way that will minimize the risk of
      obstruction. Vertical banded gastroplasty is now the only operation in use at
      UIHC for the treatment of obesity and is used not only as the primary operation
      but in all reoperations. Bypass of the stomach and duodenum is not necessary for
      weight control and adds some risk of malabsorption and duodenal and stomal ulcer
      plus a lifetime of inaccessibility of the excluded areas for diagnostic and
      therapeutic measures.

PMID- 1989110
TI  - Surgical options in postgastrectomy syndromes.
AB  - The various operations performed for the treatment of peptic ulcer disease can
      lead to a variety of iatrogenic disorders collectively referred to as the
      "postgastrectomy syndromes." Although the etiology of most of these disorders
      remains unclear, loss of vagal innervation and bypass, ablation, or destruction
      of the pylorus clearly are involved in the pathogenesis of most, if not all, of
      these disorders. Unfortunately, there often is also a poorly understood
      psychological element involved in the pathogenesis. Of all ulcer operations,
      proximal gastric vagotomy results in the fewest physiologic abnormalities and the
      mildest postoperative symptoms. The continued popularity of this operation should
      effect a marked reduction in the incidence of disabling postgastrectomy
      syndromes. Fortunately, symptoms severe enough to necessitate remedial operation
      are uncommon, and conservative medical management is always indicated and usually
      suffices. When disabling symptoms are refractory, a thorough evaluation of the
      patient and an accurate classification of the syndrome are essential to guarantee
      a satisfactory result from surgical intervention. Although numerous surgical
      procedures have been developed to deal with the different syndromes, with varied
      results, the Roux-en-Y procedure has emerged as the operation of choice for most,
      if not all, postgastrectomy syndromes. However, the Roux-en-Y procedure has not
      been universally successful, and this operation can itself lead to the recently
      recognized postgastrectomy state of Roux-en-Y stasis syndrome. Prevention
      therefore remains the best form of therapy, and remedial operation should not be
      undertaken until adequate time has elapsed since the original operation and all
      forms of conservative treatment have failed.

PMID- 1989111
TI  - Reoperation for recurrent peptic ulcer disease.
AB  - The patient with recurrent peptic ulcer evidences failure of an initial operation
      to control the ulcer diathesis. A trial of aggressive medical therapy is
      warranted in elective presentations and has a moderate chance of success. Failing
      this, we believe that reoperation should be tailored to the patient's physiologic
      status and previous operation (Table 5). Nevertheless, in most cases, we believe
      that the second operation should be the final operation and should consist of the
      procedure with the lowest recurrence rates. Therefore, we believe that the
      assurance of an adequate antrectomy and complete vagal section is the preferred
      procedure for most patients with recurrent peptic ulcer.

PMID- 1989112
TI  - Reoperation versus alternatives in retained biliary calculi.
AB  - Retained common bile duct stones can be treated by operation, dissolution,
      extraction, fragmentation, papillotomy, and reoperation. Each approach requires
      some expertise, and the likelihood of success of most depends on the composition
      and size of the stones. Good results often can be obtained nonoperatively,
      especially with a multidisciplinary team. Reoperation is rarely necessary.

PMID- 1989113
TI  - Treatment of renal cell carcinoma by extracorporeal partial nephrectomy and
      autotransplantation using splenic vascular anastomosis.
AB  - A patient with large left lower pole renal cell carcinoma in a solitary kidney is
      presented. The patient was treated by partial nephrectomy and autotransplantation
      using splenic arterial and venous anastomoses. The potential for reducing
      operative morbidity compared with autotransplantation to the iliac fossa is
      discussed.

PMID- 1989114
TI  - Emergency surgical treatment for nonvariceal bleeding of the upper part of the
      gastrointestinal tract.
AB  - Endoscopic and biochemical data were collected prospectively from 1,530 patients
      admitted with nonvariceal bleeding of the upper part of the gastrointestinal
      tract between September 1985 and June 1989. Therapeutic endoscopy was done for 93
      patients who underwent emergency surgical treatment for bleeding, subsequently
      required in 29 patients with seven postoperative fatalities. In contrast, 31
      (15.7 per cent) of 198 patients (mortality rate of 9.6 per cent at 30 days) died
      in the hospital who had undergone emergency operation in whom therapeutic
      endoscopy had not been performed; data for this latter group is now presented. At
      admission, a greater likelihood of emergency operation was associated with a
      systolic blood pressure of 100 millimeters of mercury and endoscopic stigmatas of
      recent hemorrhage (ESRH) (p less than 0.001). Rebleeding rates for the presence
      of fresh blood, active spurting and oozing hemorrhage or visible vessel in an
      ulcer base were 26.5, 28.9 and 35.9 per cent, respectively. Endoscopic stigmatas
      were thus associated with an increased risk of bleeding (p less than 0.0001) and
      rebleeding led to a sixfold increase in the mortality rate. Congestive cardiac
      failure, chronic obstructive airway disease, chronic renal failure and a history
      of previous malignant disease were each associated with postoperative mortality
      rates of more than 50 per cent. An increased risk of mortality after emergency
      operation was related to age (p less than 0.0001), preoperative (p less than
      0.002) and total (p less than 0.0001) blood transfusion requirement. Immediate
      operation after resuscitation and endoscopy was required in 87 patients; 11
      deaths (hospital mortality rate of 12.7 per cent and 9.2 per cent at 30 days)
      occurred in this group compared with 20 fatalities (18.0 per cent) documented in
      111 patients (9.9 per cent at 30 days) who underwent surgical treatment for
      rebleeding. We conclude that age, concomitant medical illness and preoperative
      and total transfusion requirements are each related to outcome after emergency
      operations. Such urgent intervention is best avoided if at all possible in
      patients with severe concomitant medical illness.

PMID- 1989115
TI  - Mechanical sutures in perforation of the thoracic esophagus as a safe procedure
      in patients seen late.
AB  - Between 1976 and 1988, we treated 13 perforations of the thoracic esophagus,
      excluding ruptured carcinoma and intraoperative wounds, by mechanical sutures
      without exclusion. The delay between perforation and treatment ranged from eight
      to 168 hours, more than 24 hours in 11. The length of perforation was 0.5 to 15.0
      centimeters. Suture was covered with a flap in ten instances; an antireflux
      procedure was associated with five instances. No digestive ostomies were
      performed. There was one death; a patient who was comatose upon arrival. The
      results of this small series suggest that myotomy exposing the mucosa and a flap
      are two essential elements of the technique; perforations of less than 6
      centimeters, even when seen late, may be treated by primary surgical closure.

PMID- 1989116
TI  - Incisional hernioplasty with Mersilene.
AB  - Thirty large incisional abdominal hernias (myoaponeurotic defects greater than 10
      centimeters) were successfully repaired by a technique of incisional hernioplasty
      which implants a large Mersilene (polyester fiber) prosthesis in the space
      between the abdominal muscles and the peritoneum. The prosthesis extends far
      beyond the borders of the myoaponeurotic defect, and is solidly held in place by
      intra-abdominal pressure and later by fibrous ingrowth. The prosthesis protects
      against recurrence in two ways. First, it prevents peritoneal eventration by
      adhering to the visceral sac and rendering it indistensible. Second, the
      prosthesis unites and consolidates the abdominal wall. Consequently, the
      procedure uniquely exploits the very force which caused the hernia to prevent a
      recurrence. A prosthesis of Mersilene is essential for success because it is
      supple and elastic enough to conform freely to the curvatures of the visceral
      sac, has the necessary grainy texture to grip the peritoneum and prevent slippage
      and is reactive enough to induce a rapid fibroblastic response to ensure
      fixation.

PMID- 1989117
TI  - Aerobic and anaerobic microbiologic factors and recovery of beta-lactamase
      producing bacteria from obstetric and gynecologic infection.
AB  - Specimens obtained from 736 patients with obstetric and gynecologic infections
      were studied for aerobic and anaerobic bacteria. Bacterial growth was present in
      714 specimens. These included 53 specimens of infected fallopian tubes, 470 of
      infected endometrium, 94 of infected amniotic fluid, 57 of aspirates of cul-de
      sacs in instances of pelvic inflammatory disease, 14 labial and vaginal abscesses
      and 26 of Bartholyn's cyst abscess. A total of 2,052 isolates (2.9 per specimen),
      1,139 anaerobes (1.6 per specimen) and 913 aerobic or facultative (1.3 per
      specimen) were recovered. The most commonly isolated anaerobic bacteria was
      Bacteroides species (566 isolates), which included Bacteroides bivius (151),
      Bacteroides fragilis group (130), Bacteroides melaninogenicus group (110) and
      Bacteroides ureolyticus (47). Others included an anaerobic gram-positive cocci
      (391), Clostridium species (48) and Fusobacterium species (36). The most
      frequently recovered aerobic and facultative bacteria were Lactobacillus species
      (169), Escherichia coli (85), Neisseria gonorrhoeae (62), Staphylococcus aureus
      (59) and Group B streptococcus (55). Three hundred and sixty-five (18 per cent)
      of the isolates recovered from 276 (39 per cent) patients were beta-lactamase
      producing organisms (BLPO); 222 (61 per cent) anaerobes and 143 (39 per cent)
      aerobes or facultatives. The most common BLPO were B. fragilis group, B. bivius,
      B. melaninogenicus, B. disiens, Enterobacteriaceae and S. aureus. These data
      illustrate the polymicrobial nature and important role of BLPO in obstetric and
      gynecologic infection.

PMID- 1989118
TI  - Simple technique for long term central venous access in the patient with
      thrombocytopenic carcinoma.
AB  - A technique for the insertion of a central venous access device in the patient
      with thrombocytopenia is described. Using the Seldinger technique, a wire is
      placed into the internal jugular vein. A catheter tunneled from the anterior part
      of the chest is inserted through a peel-away sheath into the central venous
      system. The incision is then closed.

PMID- 1989119
TI  - A simple technique for localizing nonpalpable lesions of the breast.

PMID- 1989120
TI  - Preventing kinking of the peel-away sheath during insertion of a long term
      central venous catheter using percutaneous subclavicular venipuncture.
AB  - Kinking of the peel-away sheath can prevent placement of catheters by way of
      percutaneous subclavicular venipuncture. We described a technique for overcoming
      kinking of the peel-away sheath when changing patient position and repeatedly
      dilating the catheter insertion tract which do not allow placement of the
      catheter. This technique has been used successfully in three recent instances.

PMID- 1989121
TI  - Use of terminal T-junctions for in situ bypass in the lower extremity.
AB  - This technique allows the distal anastomosis of the arterialized in situ vein to
      be performed without kinking. We have found it to be most useful when placing the
      distal portion of the mobilized segment of in situ vein into a deeply located
      infragenicular popliteal segment. We use this technique whenever a suitably
      located branch point is present.

PMID- 1989122
TI  - Theodor Kocher and the Scientific Foundation of Wound Ballistics.
AB  - The systemic and rational approach used by Kocher, coupled with his interest in
      research of wound ballistics for more than 40 years, resulted in a clear
      elucidation of the principles that form the basic scientific foundation of modern
      wound ballistics. The validity of his work has been proved repeatedly on the
      battlefields of the world for more than a century. Presently, more than ever
      before, the sound scientific precepts revealed by Kocher are essential to keep
      technologic investigation within the framework of good judgment.

PMID- 1989123
TI  - Correlation of APACHE II score, drainage technique and outcome in postoperative
      intra-abdominal abscess.
AB  - The APACHE II Score was used to stratify retrospectively severity of illness in
      91 patients postoperatively undergoing drainage of intra-abdominal abscesses. The
      method of initial abscess drainage (percutaneous or operative) was selected by
      the attending physician. The two groups of patients, those whose initial drainage
      was performed percutaneously versus operatively were similar with respect to age,
      sex, abscess location and, most importantly, severity of illness as assessed by
      the APACHE II score calculated on the day of their abscess drainage. Over-all,
      the mortality rate was 29 per cent (26 of 91 patients). Only 1.7 per cent of the
      patients with an APACHE II score of less than 15 died compared with 78 per cent
      when APACHE II was equal to or more than 15 (p less than 0.0001). Only 8 per cent
      of patients with APACHE II equal to or more than 15 undergoing percutaneous
      drainage survived compared with 30 per cent of patients who underwent surgical
      drainage procedures. While chi-square analysis demonstrated independence between
      outcome and drainage technique, outcome was dependent upon severity of illness (p
      less than 0.0005). Paradoxically, despite the attractiveness of a percutaneous
      technique for abscess drainage in the most ill patients, in this series, a
      better, although not statistically improved, chance for survival was noted with
      surgical treatment. We recommend that an objective severity scoring system be
      used whenever assessing results of treatment of intraabdominal infection and that
      surgical treatment not be avoided because the patient is considered to be too
      ill.

PMID- 1989125
TI  - [National environmental policy plan and veterinary medicine].
AB  - The main lines of environmental policy of The Netherlands are reviewed in the
      present paper. The paper particularly deals with environmental policy concerned
      with agriculture, which is most directly associated with the health of animals
      and attention is also paid to gaps in knowledge. Investigations will, for
      instance, be required on the subject of veterinary drugs which find their way
      into the environment.

PMID- 1989126
TI  - [Conservative treatment of fractures, a crooked story].

PMID- 1989124
TI  - Risk for postoperative congestive heart failure.
AB  - To identify predictors of postoperative congestive heart failure (CHF), a high
      risk population, mainly hypertensive and diabetic patients undergoing elective
      general operations, was studied. Of the 254 patients, 6 per cent had
      postoperative CHF. Among patients with preoperative cardiac disease (that is,
      previous myocardial infarction, valvular disease or CHF), 17 per cent had
      postoperative CHF; in contrast with less than 1 per cent of those without cardiac
      disease (p less than 0.001). Patients with diabetes were also at high risk (12
      versus 2 per cent, p less than 0.005), particularly those with cardiac disease.
      Patients who had equal to or greater than 40 millimeters of mercury increases or
      decreases intraoperatively in mean arterial pressure in relation to preoperative
      baseline had increased postoperative failure rates (p less than 0.02). Of note,
      postoperative failure rates were highest among patients with less than 500
      milliliters per hour of net intake (input and output) (p less than 0.03). Risk
      for postoperative CHF was restricted to patients with preoperative symptomatic
      cardiac disease and was especially high if patients also had diabetes.
      Intraoperative fluctuations in mean arterial pressure increased the probability
      of postoperative failure, while the intraoperative administration of higher net
      volumes of fluid was associated with decreased risk.

PMID- 1989127
TI  - [Surgical treatment of mammary tumors].

PMID- 1989128
TI  - [Farm euphoria].

PMID- 1989129
TI  - [Short- or long-haired domestic cat].

PMID- 1989130
TI  - [Delivery in cattle with interesting complications].
AB  - A case of dystocia in a cow delivered by Caesarean section, complicated by
      haemorrhages and a dying calf, is reported. The heifer had to be slaughtered and
      only then the clinical findings could be accounted for by close examination of
      the uterus. This case was very likely one of spontaneously reduced uterine
      torsion.

PMID- 1989131
TI  - Let's talk about it. Communication in the OR.
AB  - 1. Clear communication in the operating room promotes efficiency, reduces the
      chance of patient injury, and provides the support necessary for the staff to
      respond to high stress levels. 2. Stress, cultural or language barriers,
      differing education levels, and stereotyping are barriers to effective
      communication. 3. Positive communication techniques that are useful in the
      operating room include those that build rapport, provide support, communicate
      information, and promote problem solving.

PMID- 1989132
TI  - The controversy of flash sterilization.
AB  - 1. Flash sterilization is only recommended for emergency situations because the
      speed of the process reduces the margin of safety, increases the possibility of
      trapped air, and requires a high degree of reliability in the sterilizer. 2. When
      the weight of the instruments is increased, a greater number of organisms may be
      present and the heat up time of the sterilizer cycle will be longer. 3. If flash
      sterilization is used, it is important to know the parameters of the unit, how to
      use it, and how to transport the items so that they are protected from potential
      air-borne contaminants.

PMID- 1989133
TI  - Forging new alliances.

PMID- 1989134
TI  - Communicating when the patient cannot speak English.

PMID- 1989135
TI  - Reducing the risk of endotracheal tube fires.

PMID- 1989137
TI  - The beneficial effect of cyclosporine preloading in renal transplants from HLA
      haploidentical living donors.

PMID- 1989136
TI  - Low-dose cyclosporine is safe in renal allografts with preexisting parenchymal
      damage.

PMID- 1989138
TI  - Impact of cyclosporine on renal transplantation from elderly living donors.

PMID- 1989139
TI  - Influence of corticosteroid withdrawal on posttransplant diabetes mellitus in
      cyclosporine-treated renal transplant recipients.

PMID- 1989140
TI  - Cyclosporine withdrawal in renal transplant recipients maintained on triple
      therapy.

PMID- 1989141
TI  - Long-term results with cyclosporine immune suppression in pediatric cadaver renal
      transplantation.

PMID- 1989142
TI  - Remarkable long-term prognosis and excellent growth in kidney-transplant children
      under cyclosporine monotherapy.

PMID- 1989143
TI  - A retrospective analysis of late renal graft function: correlation with mean
      cyclosporine levels and lack of evidence for chronic cyclosporine toxicity.

PMID- 1989144
TI  - Conversion from cyclosporine: status after five years.

PMID- 1989145
TI  - Minimal sensitization and excellent renal allograft outcome following donor
      specific blood transfusion with a short course of cyclosporine.

PMID- 1989146
TI  - Improved results with combined donor-specific transfusion (DST) and sequential
      therapy protocol.
AB  - A combined DST-sequential CyA therapy protocol has been described that results in
      optimum graft survival for 1- and 2-haplotype mismatched living related donor
      recipient combinations. In addition to the excellent graft survival obtained
      through 4 years, lower prednisone and CyA dosage levels are achieved with
      significantly decreased infection rates during the posttransplant period.

PMID- 1989147
TI  - Rapamycin and cyclosporine produce synergistic but nonidentical mechanisms of
      immunosuppression.

PMID- 1989148
TI  - Lipid profiles with triple drug immunosuppressive therapy and with double drug
      combinations after renal transplantation and stable graft function.

PMID- 1989149
TI  - Increased cyclosporine levels as a result of simultaneous fluconazole and
      cyclosporine therapy in renal transplant recipients: a double-blind, randomized
      pharmacokinetic and safety study.

PMID- 1989150
TI  - A randomized prospective trial of anti-Tac monoclonal antibody in human renal
      transplantation.

PMID- 1989151
TI  - Concerted action of monoclonal antibodies directed at the P55 and P75 chains of
      the human interleukin-2 receptor.

PMID- 1989152
TI  - Immunosuppressive properties of enisoprost and a 5-lipoxygenase inhibitor (SC
      45662).

PMID- 1989153
TI  - Prophylactic use of a new immunosuppressive agent, deoxyspergualin, in patients
      with kidney transplantation from ABO-incompatible or preformed antibody-positive
      donors.

PMID- 1989154
TI  - Prevention of kidney and skin graft rejection in rats by leflunomide, a new
      immunomodulating agent.

PMID- 1989155
TI  - Markedly enhanced therapeutic effect of deoxyspergualin on acute rejection when
      combined with methylprednisolone in kidney recipients.

PMID- 1989156
TI  - Vascular rejection episodes reduce success in renal graft outcome after therapy
      with BMA 031.

PMID- 1989157
TI  - Prophylactic use of deoxyspergualin in living related renal transplantation.

PMID- 1989158
TI  - Prophylactic use of deoxyspergualin in a quadruple immunosuppressive protocol in
      renal transplantation.

PMID- 1989159
TI  - BMA 031 effectively reverses steroid-resistant rejection in renal transplants.

PMID- 1989161
TI  - Cancer development in cadaveric donor renal allograft recipients treated with
      azathioprine (AZA) or cyclosporine (CyA) or AZA/CyA.

PMID- 1989160
TI  - Cancer development in renal allograft recipients treated with conventional and
      cyclosporine immunosuppression.

PMID- 1989162
TI  - Cellular infiltrates during different immunosuppressive regimens in renal
      transplantation.

PMID- 1989163
TI  - Comparison of equine and rabbit antilymphocyte preparations in renal
      transplantation.

PMID- 1989165
TI  - Batch-to-batch variations in rabbit antithymocyte globulin preparations.

PMID- 1989164
TI  - Immunosuppressive activity of deflazacort vs methylprednisolone in renal
      transplantation: effects on lymphocyte subsets.

PMID- 1989166
TI  - Presence of donor-specific alloreactivity in histologically normal lung
      allografts is predictive of subsequent bronchiolitis obliterans.

PMID- 1989168
TI  - Importance of donor-reactive cytotoxic antibodies following cardiac
      transplantation.

PMID- 1989167
TI  - Clinical manifestations of vascular rejection in cardiac transplantation.

PMID- 1989169
TI  - Multiparous women: is routine antibody screening enough in cardiac
      transplantation?

PMID- 1989170
TI  - Impact of HLA-compatibility on rejection sequence and survival rate after
      orthotopic heart transplantation.

PMID- 1989171
TI  - HLA matching and its effect on infant and pediatric cardiac graft survival. The
      Loma Linda Pediatric Cardiac Transplant Team.

PMID- 1989172
TI  - In vitro culture of infiltrating lymphocytes from coronary arteries and
      endomyocardial biopsies: association with graft coronary disease.

PMID- 1989173
TI  - Inverse relationship between human leukocyte antigen match and development of
      coronary artery disease.

PMID- 1989174
TI  - Increased risk of rejection associated with the growth of lymphocytes from human
      cardiac allografts.

PMID- 1989175
TI  - Use of flow cytometric crossmatching in cardiac transplantation.

PMID- 1989176
TI  - Histocompatibility and other rejection risk factors in cardiac transplantation.

PMID- 1989177
TI  - The "natural history" of the transplanted lung: rates of pulmonary functional
      change in long-term survivors of heart-lung transplantation.
AB  - Long-term pulmonary function in HLT is well preserved with no evidence of
      functional decline as a result of transplant "aging," providing the allografts
      remain free of complications. Long-term survivors with OB appear to be able to
      maintain adequate oxygenation despite the marked alterations of pulmonary
      function. The ability to preserve gas exchange at reasonable levels of
      oxygenation may be the factors permitting extended survival with OB for mean
      periods of 36.0 months or greater. Preliminary studies suggest that a declining
      FEF50/FVC, at a time when pulmonary function is normal, may be an index of
      impending airway disease. Physiologically, from a long-term point of view, HLT
      remains a viable option for selected patients with end-stage cardiopulmonary
      disease.

PMID- 1989178
TI  - Analysis of survival data after transplantation and its risk factors for graft
      loss.

PMID- 1989179
TI  - Heart-lung and lung transplantation: perioperative pulmonary dysfunction.

PMID- 1989180
TI  - Cardiorespiratory and neurohormonal response to incremental maximal exercise in
      patients with denervated transplanted hearts.

PMID- 1989181
TI  - Loss of vertebral bone density in heart transplant patients.

PMID- 1989182
TI  - Four years of heart transplantation in the North Italy Transplant program (NITp).

PMID- 1989183
TI  - Detection of transplant arteriopathy: does exercise thallium scintigraphy improve
      noninvasive diagnostic capabilities?

PMID- 1989184
TI  - Use of western blotting to detect anti-heart antibodies before and after cardiac
      transplantation.

PMID- 1989185
TI  - Further studies on the natural history of obliterative bronchiolitis following
      heart-lung transplantation.

PMID- 1989187
TI  - Cystic fibrosis treated with heart-lung transplantation: North American results.

PMID- 1989186
TI  - Survival and quality of life of cystic fibrosis patients before and after heart
      lung transplantation.

PMID- 1989188
TI  - Single lung transplantation: a new therapeutic option for patients with pulmonary
      hypertension.

PMID- 1989189
TI  - Single-lung transplantation for pulmonary vascular disease.
AB  - Six patients with end-stage pulmonary vascular disease received right SLTs.
      Though patients generally had difficult early postoperative courses, four of the
      six have survived from 3 to 23 months and have achieved good recovery of right
      ventricular function and good functional results. SLT is a viable option in
      selected patients with severe pulmonary hypertension even when right ventricular
      function is severely impaired.

PMID- 1989190
TI  - Single-lung transplantation for obstructive airway disease.

PMID- 1989191
TI  - The distribution of ventilation and perfusion after single-lung transplantation
      in patients with pulmonary fibrosis and pulmonary hypertension.

PMID- 1989192
TI  - Prospective analysis of serial pulmonary function studies and transbronchial
      biopsies in single-lung transplant recipients.

PMID- 1989193
TI  - Mucociliary function after lung transplantation.

PMID- 1989194
TI  - Late pulmonary complications of isolated lung transplantation.

PMID- 1989195
TI  - Changes in cardiac morphology and function following single-lung transplantation.

PMID- 1989196
TI  - Accelerated posttransplant coronary arteriosclerosis in combined heart-lung
      transplantation.

PMID- 1989197
TI  - Accelerated arteriosclerosis in heart transplant recipients: an immunopathology
      study of 22 transplanted hearts.

PMID- 1989198
TI  - Combined harvest of heart and lungs: techniques and results.

PMID- 1989199
TI  - Is cyclosporine indicated in HLA-identical renal transplant recipients?

PMID- 1989200
TI  - Long-term results in cadaveric renal transplantation under cyclosporine therapy.

PMID- 1989201
TI  - Posttransplant diabetes mellitus in cyclosporine-treated renal transplant
      recipients.

PMID- 1989202
TI  - Effect of cyclosporine on the clinical course of HBsAg-positive renal transplant
      patients.

PMID- 1989203
TI  - Efficacy of induction therapy in cadaveric renal transplantation comparing rabbit
      antithymocyte serum and Minnesota antilymphoblast globulin.
AB  - From August 1986 to July 1989, 98 patients receiving primary cadaveric kidney
      transplants received either RATS (n = 50) or MALG (n = 48) during the induction
      phase of a quadruple immunosuppressive protocol. Patient groups were well
      matched. The duration of RATS and MALG treatment and the time of CyA induction
      were equivalent. Serum creatinine and rejection episodes up to 1 year were not
      statistically different. Hematologic side effects resulted in dose reduction of
      MALG in 42% of patients without adverse rejection results. In the RATS group, no
      dosage reductions were required. One-year patient survivals (96% to 100%), and 1
      year graft survival (82% to 85%) were not significantly different in the 2
      groups. Infectious complications were 30% higher in the MALG group and a
      significant factor in 2 deaths. Monitoring of lymphocyte subsets revealed
      insignificant differences in the percent of decrease of each cell population
      between MALG and RATS groups during induction.

PMID- 1989205
TI  - The clinical and biochemical effect of calcium channel blockers in organ
      transplant recipients on cyclosporine.

PMID- 1989204
TI  - Reversal of cyclosporine-associated hemolytic-uremic syndrome by plasma exchange
      with fresh-frozen plasma replacement in renal transplant recipients.

PMID- 1989206
TI  - Evidence against chronic progressive cyclosporine nephrotoxicity.

PMID- 1989207
TI  - Early rejection: determining the fate of renal transplants.

PMID- 1989208
TI  - Long-term results after cadaver kidney transplantation have also improved over
      the last two decades. The Leuven Collaborative Group for Transplantation.

PMID- 1989210
TI  - The clinical course of chronic declines in renal allograft function.

PMID- 1989209
TI  - Early glomerulopathy in kidneys transplanted into diabetic patients.

PMID- 1989211
TI  - Effect of anti-Fab antibodies on renal allografts.

PMID- 1989212
TI  - Monitoring serum IL-2R levels in cadaver renal transplantation: a prospective,
      blinded study.

PMID- 1989213
TI  - Predictive factors for immunologic graft failure in cadaver renal transplant
      recipients.

PMID- 1989214
TI  - Matching cadaver transplants achieve graft survivals comparable to living related
      transplants.

PMID- 1989215
TI  - Tumour necrosis factor in renal transplantation.

PMID- 1989216
TI  - Immunologic tolerance in human transplantation: does a maternal effect exist?

PMID- 1989217
TI  - Predictive value of pretransplant IL-2 levels in kidney transplantation.

PMID- 1989218
TI  - Clinical relevance of donor-specific IgG determination by FACS analysis in renal
      transplantation.

PMID- 1989219
TI  - Role of cold ischemia time and vascular rejection in renal grafts from elderly
      donors.

PMID- 1989220
TI  - Biochemical multisensor element for estimation of organ viability.

PMID- 1989221
TI  - Economic impact of delayed graft function.

PMID- 1989222
TI  - Clinical comparison of UW with Collins' solution for cadaveric kidney
      preservation.

PMID- 1989223
TI  - Ca(++)-induced modulation of erythropoiesis in polycythemic transplanted
      patients.

PMID- 1989224
TI  - The center effect in kidney transplantation.

PMID- 1989225
TI  - A report of 504 six antigen-matched transplants.

PMID- 1989226
TI  - A comparison of donor-specific and random transfusions in living-related renal
      transplantation and their effect on steroid withdrawal.

PMID- 1989227
TI  - The fate of paired kidneys: recipient immunologic risk factors profoundly
      influence immediate posttransplant renal function.

PMID- 1989228
TI  - Are black living-related renal donors at greater long-term risk of renal
      complications than white donors?

PMID- 1989229
TI  - Prognostic indices for first and second transplants can predict kidney graft
      survival.

PMID- 1989230
TI  - Renal function of transplanted kidneys harvested during cardiopulmonary bypass
      with profound hypothermia.

PMID- 1989232
TI  - Kidney retransplantation: patients with a failed second kidney transplant should
      be considered for a third transplant.

PMID- 1989231
TI  - Kidney protective effect of diltiazem after renal transplantation with long cold
      ischemia time and triple-drug immunosuppression.

PMID- 1989233
TI  - Long-term outcome in 1-year graft survivors: comparison of diabetic and
      nondiabetic populations.

PMID- 1989234
TI  - Intraoperative blood volume expansion induces primary function after renal
      transplantation: a study of 96 paired cadaver kidneys.

PMID- 1989235
TI  - Long-term follow-up of 40 untreated cadaveric kidney transplant renal artery
      stenoses.

PMID- 1989236
TI  - Kidney transplantation: absolute and relative psychologic contraindications.

PMID- 1989237
TI  - Update and outcome of renal transplant patients with human immunodeficiency
      virus. The Groupe Cooperatif de Transplantation de I'lle de France.

PMID- 1989238
TI  - Effect of steroid withdrawal on hypertension and cholesterol levels in living
      related recipients.

PMID- 1989239
TI  - Donor age and cause of death affect cadaver renal allograft outcome.

PMID- 1989240
TI  - De novo cancer after pediatric kidney transplantation.

PMID- 1989241
TI  - Lipid and lipoprotein abnormalities in children on hemodialysis and after renal
      transplantation.

PMID- 1989242
TI  - Renal transplantation in small children with congenital nephrotic syndrome of the
      Finnish type.

PMID- 1989243
TI  - Transplanted children with long-term graft function have an excellent quality of
      life.

PMID- 1989244
TI  - Successful kidney transplantation in infants.

PMID- 1989245
TI  - Progression of infantile cystinosis after renal transplantation.

PMID- 1989246
TI  - Anti-CD25 monoclonal antibody prevents early rejection in liver transplantation-
      a pilot study.

PMID- 1989248
TI  - Combination immunosuppression with azathioprine reduces the incidence of
      ductopenic rejection and vanishing bile duct syndrome after liver
      transplantation.

PMID- 1989247
TI  - The anti-IL-2 receptor monoclonal antibody YTH-906 in liver transplantation.

PMID- 1989249
TI  - Peribiliary vascular diseases in rejected livers; computer-aided three
      dimensional reconstruction and morphometry.

PMID- 1989250
TI  - Reversible vanishing bile duct syndrome after liver transplantation: report of 6
      cases.

PMID- 1989251
TI  - Soluble interleukin-2 receptor in liver transplant recipients.

PMID- 1989252
TI  - Tumor necrosis factor alpha and interleukin-1 beta in rejecting human liver
      grafts.

PMID- 1989253
TI  - Comparison of ELISA and a flow cytometric method in the daily monitoring of
      soluble interleukin 2 receptors in liver transplant recipients.

PMID- 1989254
TI  - MHC expression on human hepatocytes before and after isolation.

PMID- 1989255
TI  - Sequential IL-2 and IL-2R levels predict rejection in liver allograft recipients.

PMID- 1989257
TI  - Reduced incidence of rejection in patients undergoing liver transplantation for
      chronic hepatitis B.

PMID- 1989256
TI  - Impact of serum lipid parameters on the diagnosis of acute and chronic rejection
      after orthotopic liver transplantation.

PMID- 1989258
TI  - Development of Kaposi's sarcoma in liver transplant recipients: characteristics,
      management, and outcome.

PMID- 1989259
TI  - Increased bile duct complications in ABO incompatible liver transplant
      recipients.

PMID- 1989260
TI  - Severe ductopenic rejection with features of vanishing bile duct syndrome:
      clinical, biochemical, and histologic evidence for spontaneous resolution.

PMID- 1989261
TI  - The effect of cyclosporine A on long-term renal function in pediatric liver
      transplant recipients.

PMID- 1989262
TI  - Analysis of liver graft loss in infants and children below 4 years.

PMID- 1989263
TI  - Orthotopic liver transplantation in patients over 60 years of age.

PMID- 1989264
TI  - Long-term analysis of glomerular filtration rate and hypertension in adult liver
      transplant recipients treated with cyclosporine A.

PMID- 1989266
TI  - Bone disease in liver transplant recipients: incidence, timing, and risk factors.

PMID- 1989265
TI  - Is selective decontamination of the digestive tract beneficial in liver
      transplant patients? Interim results of a prospective, randomized trial.

PMID- 1989267
TI  - Renal function following liver transplantation in children.

PMID- 1989268
TI  - Long-term renal function in liver transplantation.

PMID- 1989269
TI  - Neuropathological findings in autopsies after liver transplantation.

PMID- 1989270
TI  - The surgical implications of the posttransplant lymphoproliferative disorders.

PMID- 1989271
TI  - Hyperlipidemia and obesity after orthotopic liver transplantation.

PMID- 1989272
TI  - Vascular complications following orthotopic liver transplantation: outcome and
      the role of urgent revascularization.

PMID- 1989273
TI  - Early graft loss after liver transplantation: etiology, chronology, and
      prognosis.

PMID- 1989274
TI  - Use of cyclosporine with poor initial renal function results in severely
      diminished renal clearance up to three years following liver transplantation.

PMID- 1989275
TI  - HBV infection after liver transplantation in HBsAg positive patients: experience
      with long-term immunoprophylaxis.

PMID- 1989276
TI  - Fungal disease in liver transplant recipients: a multivariate analysis of risk
      factors.

PMID- 1989277
TI  - Analysis of severe infections (INF) after 180 consecutive liver transplants: the
      impact of amphotericin B prophylaxis for reducing the incidence and severity of
      fungal infections.

PMID- 1989278
TI  - A comparison between heterotopic and orthotopic liver transplantation in patients
      with end-stage chronic liver disease.

PMID- 1989279
TI  - A totally failing liver may be more harmful than no liver at all: three cases of
      total hepatic devascularization in preparation for emergency liver
      transplantation.

PMID- 1989280
TI  - The predictive value of donor liver biopsies on the development of primary
      nonfunction after orthotopic liver transplantation.

PMID- 1989281
TI  - The outcome of steatotic grafts in liver transplantation.

PMID- 1989282
TI  - Quality of life after liver transplantation: can a psychosocial support program
      contribute?

PMID- 1989283
TI  - Dividing the liver for the purpose of split grafting or living related grafting:
      a search for the best cutting plane.

PMID- 1989284
TI  - Hepatic preservation with University of Wisconsin solution is associated with
      reduced allograft rejection.

PMID- 1989285
TI  - Cold ischemia time vs outcome of human liver transplantation using UW solution.

PMID- 1989286
TI  - UW solution protects against reperfusion injury by inhibiting lipid peroxidation.

PMID- 1989287
TI  - Initial flush solution for donor liver procurement: lactated Ringers' or UW
      solution? A randomized, prospective trial.

PMID- 1989288
TI  - Liver and kidney transplantation in the treatment of primary hyperoxaluria.

PMID- 1989289
TI  - Prevention of recurrent thrombosis following liver transplantation for Budd
      Chiari syndrome associated with myeloproliferative disorders: treatment with
      hydroxyurea and aspirin.

PMID- 1989290
TI  - Utilization, paediatric donor livers: failure to utilize available paediatric
      livers donated in the UK.

PMID- 1989291
TI  - A comparative study of patients undergoing liver transplantation for primary
      sclerosing cholangitis and primary biliary cirrhosis.

PMID- 1989292
TI  - Survival after liver transplantation in diabetics.

PMID- 1989294
TI  - Intraoperative systemic and hepatic hemodynamics associated with fulminant
      hepatic failure: comparison with chronic end-stage liver disease.

PMID- 1989293
TI  - Is orthotopic liver transplantation a feasible treatment for secondary cancer of
      the liver?

PMID- 1989295
TI  - Retrospective evaluation of liver transplantation for cirrhosis: a comparative
      study of 100 patients with or without previous porto-systemic shunt.

PMID- 1989296
TI  - Assessment of short-term prognosis in liver transplant candidates with
      postnecrotic or biliary cirrhosis.

PMID- 1989297
TI  - Functional state of the donor liver and early outcome of transplantation.

PMID- 1989298
TI  - Liver transplantation in infants weighing less than 10 kilograms.

PMID- 1989299
TI  - Definitive corticosteroid withdrawal following simultaneous pancreas and kidney
      transplantation.

PMID- 1989300
TI  - Synergistic effect of cyclosporine and mizoribine on canine pancreas allograft
      survival.

PMID- 1989301
TI  - Effect of short-term high-dose cyclosporine treatment of endocrine function of
      segmental pancreatic grafts.

PMID- 1989302
TI  - Serum markers for pancreas rejection: long-term behavior following clinical
      pancreatico-duodenal transplantation.

PMID- 1989303
TI  - Pancreas transplant pathology: an immunohistochemical comparison of allografts
      with rejection, syngeneic grafts, and chronic pancreatitis.

PMID- 1989304
TI  - Effect of ex vivo perfusion using anti-class II monoclonal antibody on the
      rejection of canine pancreaticoduodenal allografts.

PMID- 1989305
TI  - Pancreas specific protein (PASP) monitoring in pancreas transplantation.

PMID- 1989306
TI  - Correlation of pancreas allograft biopsy with radionuclide and ultrasound imaging
      of pancreas allografts.

PMID- 1989307
TI  - Lower urinary tract complications in patients with duodenocystostomies for
      exocrine drainage of the transplanted pancreas.

PMID- 1989308
TI  - Activated proteolytic enzymes in the urine of whole organ pancreas transplant
      patients with duodenocystostomy.

PMID- 1989310
TI  - Control of metabolic acidosis after pancreas transplantation using acetazolamide.

PMID- 1989309
TI  - Detrimental effects of fluid and electrolyte loss from duodenum in bladder
      drained pancreas transplants.

PMID- 1989311
TI  - Electrolyte imbalance after canine pancreaticoduodenal allotransplantation using
      duodenocystostomy technique.

PMID- 1989312
TI  - Combined experience with immediate pancreas retransplantation.

PMID- 1989313
TI  - Factors influencing pancreas transplant outcome: Cox proportional hazard
      regression analysis of a single institution's experience with 357 cases.

PMID- 1989314
TI  - Short-term and long-term effects of HLA matching in cadaveric pancreas
      transplantation.

PMID- 1989315
TI  - Solitary pancreas transplantation: alone in nonuremic and after a kidney in
      uremic diabetic patients.

PMID- 1989316
TI  - Effect of simultaneous liver retrieval, retrieval team, and preservation time on
      cadaver whole-organ, bladder-drained pancreatic allograft survival rates.

PMID- 1989318
TI  - The changes in prostaglandins after segmental pancreatic transplantation.

PMID- 1989317
TI  - Increased thromboxane production by the pancreas after 24-hour preservation in UW
      1 solution.

PMID- 1989319
TI  - The hemodynamic time course of the pancreas after segmental autotransplantation
      in dogs.

PMID- 1989320
TI  - Effect of preservation on blood flow and production of prostacyclin and
      thromboxane A2 in canine segmental pancreatic autografts.

PMID- 1989321
TI  - The effect of donor-specific blood transfusion on canine pancreas allograft
      survival.

PMID- 1989322
TI  - Long-term glucose control following combined kidney and pancreatic
      transplantation.

PMID- 1989323
TI  - Effects of pancreatic transplantation on diabetic polyneuropathy.

PMID- 1989324
TI  - Improvement in autonomic function following combined pancreas-kidney
      transplantation.

PMID- 1989326
TI  - Effect of successful renal and segmental pancreatic transplantation on peripheral
      and autonomic neuropathy.

PMID- 1989325
TI  - Improved glucose counterregulation after pancreas transplantation in diabetic
      patients with unawareness of hypoglycemia.

PMID- 1989327
TI  - Lipid metabolism after successful kidney and pancreatic transplantation.

PMID- 1989328
TI  - Temporary or permanent suppression of exocrine secretion in canine pancreatic
      grafts.

PMID- 1989329
TI  - Extensive decrease in insulin secretion by the pancreas preserved for 24 hours in
      UW-1 solution.

PMID- 1989330
TI  - Experimental pancreaticoduodenal allotransplantation in litter mate and random
      mate dogs with or without cyclosporine.

PMID- 1989331
TI  - Influence of islet mass and purity on reversibility of diabetes in
      pancreatectomized pigs.

PMID- 1989332
TI  - Noninvasive assessment of cardiac risk in insulin-dependent diabetic patients
      being evaluated for pancreatic transplantation using thallium-201 myocardial
      perfusion scintigraphy.

PMID- 1989333
TI  - Use of monoclonal antibodies in vivo as a therapeutic strategy for acute GvHD in
      matched and mismatched bone marrow transplantation.

PMID- 1989335
TI  - Allogeneic bone marrow transplantation for leukemia using chemotherapy as
      conditioning: 6-year results of a single institution trial.

PMID- 1989334
TI  - Interleukin-2 infusion after autologous bone marrow transplantation enhances
      hemopoietic regeneration.

PMID- 1989336
TI  - Marrow transplantation versus chemotherapy for adult patients with acute
      lymphoblastic leukemia: results of a clinical study.

PMID- 1989337
TI  - Transfected cells and transgenic mice.

PMID- 1989339
TI  - Organ donation--1990.

PMID- 1989338
TI  - Application of molecular genetics to transplantation immunology.

PMID- 1989340
TI  - An evaluation of a local variance of the United Network for Organ Sharing (UNOS)
      point system on the distribution of cadaver kidneys to waiting minority
      recipients. Medical Advisory Committee, the Regional Organ Bank of Illinois.

PMID- 1989341
TI  - Three years of experience with a 'presumed consent' legislation in Belgium: its
      impact on multi-organ donation in comparison with other European countries. The
      Leuven Collaborative Group for Transplantation.

PMID- 1989342
TI  - The use of marginal donors for organ transplantation: the older and younger
      donors.

PMID- 1989343
TI  - Twenty percent more kidneys through a non-heart beating program.

PMID- 1989344
TI  - Is unrelated living donor a valid organ source in renal transplantation under CyA
      therapy?

PMID- 1989346
TI  - Smooth muscle cell proliferation by conditioned media from cyclosporine-treated
      endothelial cells: a role of endothelin.

PMID- 1989345
TI  - The in vivo effect of cyclosporine on interleukin-6 gene expression in renal
      transplant recipients.

PMID- 1989347
TI  - Prevention of chronic cyclosporine nephrotoxicity in renal transplantation by
      picotamide.

PMID- 1989348
TI  - Doppler spectrum analysis can detect immediate hemodynamic effects of
      cyclosporine infusion on human kidney grafts.

PMID- 1989349
TI  - Cyclophilin binding: a more accurate measure of cyclosporine immunosuppressive
      activity after renal transplantation.

PMID- 1989350
TI  - Cyclosporine reversibly inhibits natural killer-cell activity.

PMID- 1989351
TI  - Molecular mechanism of cyclosporine A drug interactions: inducers and inhibitors
      of cytochrome P450 screening in primary cultures of human hepatocytes.

PMID- 1989352
TI  - Assessment of the biological activity of cyclosporine metabolites using the human
      JURKAT cell line.

PMID- 1989353
TI  - A pharmacoeconomic intrapatient comparison of Sandimmune capsules and Sandimmune
      oral solution in kidney transplant recipients.

PMID- 1989354
TI  - Randomized prospective trial of elective cyclosporine withdrawal from triple
      therapy at 6 months after cadaveric renal transplantation.

PMID- 1989355
TI  - Randomized controlled trial of steroids versus no steroids in stable cyclosporine
      treated renal graft recipients.

PMID- 1989356
TI  - Long-term results of cyclosporine monotherapy in kidney transplantation.

PMID- 1989357
TI  - Cadaveric renal transplant without prophylactic prednisone therapy.

PMID- 1989358
TI  - Cyclosporine monotherapy after kidney transplantation since 1983.

PMID- 1989360
TI  - [Acquired severe aplastic anemia. Therapeutic effect and prognosis after
      allogeneic bone marrow transplantation].
AB  - During 1980-1988 bone marrow transplantation was performed in 14 patients with
      acquired severe aplastic anemia. Twelve of these patients had HLA identical and
      two patients incompatible family donors. Two patients died before marrow
      engraftment. Twelve patients engrafted 12-30 days after marrow transplantation
      with continued normal marrow function. The actuarial probability for long term
      survival was found to be 67% after HLA identical allogeneic sibling marrow
      transplantation. The longest time of observation was 9 years and the patient is
      still alive. All deaths occurred during the first six months posttransplant. It
      is concluded that the serious prognosis for patients with SAA has improved if the
      patients have the possibility for allogeneic HLA identical family donor
      transplantation.

PMID- 1989359
TI  - Comparison of antilymphocyte globulin and continuous i.v. cyclosporine A as
      induction immunosuppression for cadaver kidney transplants: a prospective
      randomized study.

PMID- 1989361
TI  - [Absence because of infectious diseases among children attending day care
      institutions in a county].
AB  - A retrospective investigation was undertaken of the connection between absence on
      account of illness and the hygienic routines in 28 day institutions in the County
      of Storstrom. A total of 953 children aged 0-6 years were involved. Absence on
      account of illness was described on the basis of registration for three months
      carried out by the staffs of the day institutions. On the basis of information
      about sick-leave, interview investigations were carried out the hygienic routines
      in the six day institutions which showed the highest and lowest absenteeism on
      account of illness, respectively. Only slight differences were found in the
      hygienic routines in the institutions investigated and no connections were found
      between sickness and hygiene. On the other hand, there appears to have been a
      connection between absence on account of illness and time spent out-of-doors; the
      greatest illness being observed in the institutions where the children spent
      least time out-of-doors. With the object preventions of illness among children in
      day institutions, further investigations concerning the significance of time
      spent out-of-doors and the indoor environment for these children would be of
      interest.

PMID- 1989362
TI  - [Hearing loss among premature and full-term infants in Rinkobing county. Results
      of tone and speech audiometry].
AB  - A material of 101 out of 111 premature infants admitted with gestational ages
      less than or equal to 35 weeks and birth weights less than or equal to 2,000 g to
      the Paediatric Department, Herning Central Hospital during the years 1977-1980
      and 101 infants born at term and matched for age and sex were investigated with
      pure-tone audiometry in quiet surroundings and speech-audiometry in noisy
      surroundings in the Ringkobing County Audiological Department in Holstebro. Where
      all frequencies were concerned, we found slightly more children from the
      premature group with hearing thresholds greater than 15 dB HL. One premature
      child had been equipped with a hearing aid (HA) at the age of 6 1/2 years on
      account of a hearing threshold in the best ear of 55 dB HL for all frequencies.
      Two children in the premature group had unrecognized hearing loss in the best ear
      between 30-40 dB HL for the average of the frequencies 500, 1,000 and 2,000 Hz.
      One of these children was equipped with a hearing aid. None of the children in
      the control group had hearing loss justifying a hearing aid. Good agreement was
      found between speech audiometry in noisy surroundings carried out with the Danish
      test material "Dantale" and pure-tone audiometry. In this group, speech
      audiometry did not provide further information as compared with pure-tone
      audiometry. Although only few children with severe hearing defects were found, it
      is important that these are detected as soon as possible in view of their
      intellectual development. Premature infants constitute a risk group for defective
      hearing.

PMID- 1989363
TI  - [The significance of recurrent nerve paresis for the operability of lung cancer].
AB  - The object of the study was a reassessment of the old but still widely accepted
      apophthegm that recurrent nerve palsy prohibits surgery in patients with
      pulmonary cancer. Out of 1,279 patients admitted over a 10-year period with
      proven or suspected pulmonary cancer, 23 were found to have recurrent nerve
      paralysis. Eleven of these were found inoperable by the preoperative work-up
      while 12 underwent thoracotomy. In three cases it was possible to perform a left
      upper lobectomy, which was considered to be radical both macro- and
      microscopically in two cases. The conclusion is that paralysis of the recurrent
      nerve, as might be foreseen, gravely worsens the prognosis, inverting the usual
      ratio of 80:20 between resections and exploratory thoracotomies. This, however,
      leaves a small group which will benefit from surgery, particularly considering
      the lack of alternative therapy.

PMID- 1989364
TI  - [Possible causes of infection in hip alloplasty].
AB  - In order to illustrate possible causes of infection following arthroplastic hip
      operations, a retrospective review was undertaken of all operations of this type
      carried out during the period 1 May 1985 to 1 August 1988 in the Department of
      Orthopaedic Surgery, Herlev Hospital. A total of 127 operations on 126 patients
      were undertaken. Deep infection occurred in eight patients. Suggestions are made
      for reduction of this high frequency of infection.

PMID- 1989365
TI  - [Long-term treatment of chronic bronchitis with pulmonary physiotherapy with and
      without positive expiratory pressure].
AB  - In a prospective, randomized, controlled study, treatment of chronic bronchitis
      with self-administered chest physiotherapy alone (control) or with positive
      expiratory pressure (PEP) by mask was studied. Forty-three patients completed the
      study (n = 20 PEP, and n = 23 control). After instruction, the treatments were
      self-administered twice daily for 12 months (34 patients) and five months (9
      patients). The patients completed a diary concerning symptoms twice weekly. An
      acute exacerbation (AE) was defined as the appearance of mucopurulent or purulent
      sputum and increasing cough and one or more of the following symptoms:
      temperature greater than or equal to 38 degrees C, general malaise, increased
      dyspnea, increased mucus production, increased thickness of mucus or increased
      difficulty in expectoration. The number of AE were calculated from the diaries.
      The incidence of AE was significantly lower in the PEP group (p less than
      0.0005). In the PEP group, three patients had a total of six AE, compared to 12
      patients with 28 AE in the control group. The PEP group also used less
      antibiotics (p less than 0.005). Treatment with a simple PEP device can reduce
      morbidity in patients with chronic bronchitis.

PMID- 1989366
TI  - [Anti-cardiolipin antibody in cerebral infarction].
AB  - A 28 year old woman with a previous history of labile hypertension, migraine and
      transitory cerebral ischemia was admitted with cerebral infarction. One month
      later she developed livedo reticularis and amaurosis fugax, which led to the
      diagnosis of Sneddon's disease (livedo reticularis, labile hypertension and
      neurological symptoms) and the anticardiolipin antibody (ACA) syndrome. Treatment
      with prednisone and phenprocoumon resulted in lowering of ACA-titers, but the
      symptoms did not subside until acetylsalicylic acid was added.

PMID- 1989367
TI  - [Aspiration of a broken silver cannulas into the trachea].
AB  - A case in which a silver cannula broke and was aspirated into the trachea is
      presented. Examination of the silver cannula in the Institute of Technology in
      Jutland revealed that the soldering of the throat plate was defective. In
      addition, the cannula was made of nickel silver plated with silver. It is
      proposed that only cannulae made of precious metal should be employed and that
      the construction of cannulae made if precious should be altered e.g. the throat
      plate could be surrounded with muff a 4-5 mm in height which would provide a
      greater soldering area and thus increase the strength of the connection. An
      example of poor soldering with increased risk of breaking is shown so that the
      stocks of cannulae can be inspected and sorted out.

PMID- 1989368
TI  - [Hepatitis B transmitted by ear-piercing].
AB  - A case of hepatitis B occurred in connection with piercing the earlobes for ear
      rings. The most probable source of infection was repeated use of the instruments
      following disinfection in hydrogen peroxide. Disposable instruments are therefore
      recommended for this procedure.

PMID- 1989369
TI  - [Coloanal reservoir in low rectal cancer].
AB  - On the basis of a case history a method of treating low rectal cancer is
      presented. The method includes resection of the rectum and mucosal protectomy
      with establishment of a colo-anal reservoir.

PMID- 1989370
TI  - [Painter's syndrome or presenile dementia--an enormous overdiagnosing with high
      human and economic costs].

PMID- 1989371
TI  - [Urinary tract problems among aged women in nursing homes can often be treated by
      educational measures].

PMID- 1989372
TI  - [A 20-year prospective study of osteoporosis--is it necessary?].

PMID- 1989373
TI  - [General anesthesia with or without gas. The veterinary solution].

PMID- 1989374
TI  - [Sotalol (Sotacor). A different beta blockader with class II and III anti
      arrhythmia].

PMID- 1989376
TI  - [The polymerase chain reaction used in microbiologic diagnosis].
AB  - Among the new DNA technological methods for microbiological diagnosis, the most
      promising seems to be the polymerase chain reaction (PCR). The sensitivity of the
      method is approximately 100% and the specificity is between 90% and 100%,
      depending on the availability of an already existing test sufficient for
      comparison. The PCR is able to detect only one microorganism in clinical samples.
      Because of this high sensitivity, contamination of samples is one of the major
      problems. After certain preparation procedures, the method can be used on
      different kinds of human sample material. The PCR could be used for detection of
      a microorganism, for detection of a single gene (toxin gene) or for typing of
      microorganisms. It is expected that, in the immediate future PCR will be a
      prominent part of the methods used in microbiological diagnosis.

PMID- 1989375
TI  - [War surgery--problem of others?].

PMID- 1989377
TI  - [Antiphospholipid antibodies].
AB  - Antiphospholipid antibodies (APA) are acquired, circulating immunoglobulins
      connected with thrombo-embolic diseases occurring within all organ systems.
      Whether the antibodies are of pathogenetic relevance for the development of
      thrombo-embolic states is unresolved. All materials are limited and have yielded
      contradictory results with regard to important aspects. An increased APTT or PTT
      does not increase the risk of bleeding in patients with LA, unless abnormalities
      in the coagulation process are present, e.g. thrombocytopenia or
      hypoprothrombinaemia. Many questions are unanswered: Should APA be treated in
      asymptomatic patients? Should patients with APA and relevant symptoms be treated?
      If so, which treatment should be chosen? And how long should the treatment
      continue? Are APA of pathogenetic importance or are they markers for another
      mechanism that causes an immunocoagulopathy? How can it be explained that so many
      persons produce autoantibodies without becoming seriously ill? In order to
      clarify the significance of APA it is necessary to standardize tests and to
      perform extensive, prospective studies, where variations of ACA titres are
      analysed. Until results from such studies are available, APA should be looked for
      in patients with recurring arterial or venous thrombosis and in patients with
      recurring spontaneous abortion with reference to anticoagulant and anti-platelet
      aggregation therapy if IgG-ACA are elevated over prolonged periods.

PMID- 1989378
TI  - [Experiences of war surgery from the civil war in Afghanistan].
AB  - The authors describe their experience of war surgery from a period of three
      months. A total of 635 patients, most of whom were young men, were treated. The
      journey to hospital was frequently very long, often lasting for several days. The
      lesions and types of surgery are described. Ketamine was found to be very useful
      for war anaesthesia.

PMID- 1989380
TI  - Helper virus-dependent replication, nucleotide sequence and genome organization
      of the satellite virus of maize white line mosaic virus.
AB  - Virus like particles (17 nm in diameter) associated with maize white line mosaic
      virus (MWLMV) were shown to be a satellite virus of MWLMV (SV-MWLMV) on the basis
      of the following properties: (1) The SV-MWLMV was dependent upon the presence of
      MWLMV for replication in maize, while the latter virus could replicate
      independently of the SV particles. (2) No nucleotide sequence homology was
      detected between the SV-MWLMV and MWLMV, using complementary DNA probes prepared
      to the two RNAs, in a Northern blot hybridization analysis. (3) The RNA of the SV
      MWLMV translated in vitro to produce a protein of the same Mr (24,000) as that
      found associated with the SV particles. This protein could be immunoprecipitated
      with an antiserum to the SV particles. And (4), there was no serological
      relationship between the coat proteins of MWLMV and the SV-MWLMV. The complete
      nucleotide sequence of the SV-MWLMV RNA (1168 nucleotides) was determined. The SV
      MWLMV RNA contains a single open reading frame encoding a polypeptide of Mr
      23,961. Computer analysis revealed no significant homology between SV-MWLMV RNA
      and any other viral or satellite RNAs. However, the putative SV-MWLMV capsid
      protein is predicted to share some structural features with the capsid protein of
      the satellite virus of panicum mosaic virus.

PMID- 1989379
TI  - Two cases of a renal epithelial tumour resembling immature nephron.
AB  - Two cases of renal epithelial tumours are reported in females aged 46 and 66
      years respectively. In spite of the large size of the tumours, neither invasive
      growth nor metastasis was observed. Histologically, the tumours were composed of
      immature epithelial cells forming tubules with abortive glomeruloid structures.
      Electron microscopy of tumour cells revealed poorly developed polarity and
      intracytoplasmic organelles. They showed similar immunohistochemical reactions to
      those of developing nephrons, particularly to those of the S-shaped body. The
      nuclear DNA content of the tumour cells was almost euploid. We conclude that the
      lesions were epithelial tumours of the kidney histologically mimicking developing
      renal parenchyma.

PMID- 1989381
TI  - Identification and characterization of the IE-1 gene of Orgyia pseudotsugata
      multicapsid nuclear polyhedrosis virus.
AB  - The IE-1 gene of Orgyia pseudotsugata multicapsid nuclear polyhedrosis virus
      (OpMNPV) was mapped between 95.7 and 97.1 map units on the viral genome. Sequence
      analysis of the OpMNPV IE-1 gene (OpIE-1) identified an open reading frame that
      coded for a predicted protein of 560 amino acids with a molecular weight of
      64,775. Transcriptional analysis of OpMNPV-infected Lymantria dispar (LD652Y)
      cells identified two RNAs homologous to the OpIE-1 open reading frame that were
      1.7 and 1.9 kb in size. The 1.7-kb transcript could be detected by 0 hr
      postinfection (hr p.i.) and the steady-state levels increased up to 48 hr p.i.
      The 1.9-kb message appears to be spliced and has peak expression from 4 to 6 hr
      p.i. but can still be detected at late times p.i. Comparison of the OpIE-1 and
      Autographa californica multicapsid nuclear polyhedrosis virus (AcMNPV) IE-1
      predicted proteins revealed that the N-terminal region had very low sequence
      identity (21%) but had maintained an acidic profile, whereas the C-terminal
      region showed 55% amino acid identity. Transient assay analysis showed that OpIE
      1 was able to trans-activate the AcMNPV delayed early reporter gene construct
      p39CAT in both LD652Y cells and Spodoptera frugiperda (Sf9) cells. The expression
      of p39CAT trans-activated by OpIE-1 was also found to be enhanced by the AcMNPV
      hr enhancer sequences. The OpIE-1 promoter was linked to the chloramphenicol
      acetyl transferase gene and deletion analysis was used to identify regions
      involved in the regulation of this gene. This analysis revealed that the OpIE-1
      promoter contained regions that were responsive to a transcriptional activator
      that was specific to Sf9 cells. In addition it was shown that OpIE-1 could trans
      activate its own promoter and that for maximal expression this required sequences
      between -420 and -330 relative to the transcriptional start site. These data
      suggest that OpIE-1 is autoregulated during normal viral infection of insect
      cells.

PMID- 1989382
TI  - Cloning of the maize rough dwarf virus genome: molecular confirmation of the
      plant-reovirus classification scheme and identification of two large
      nonoverlapping coding domains within a single genomic segment.
AB  - The segmented double-stranded RNA genome of maize rough dwarf virus, a plant
      infecting reovirus of the genus Fijivirus, was cloned and partially
      characterized. Nucleotide sequence analysis of full-length cDNA clones
      corresponding to genomic segments S6, S7, and S8 revealed each segment to contain
      the conserved terminal oligonucleotide sequences (+) 5' AAGUUUUUU------UGUC 3'
      and adjacent, segment-specific, regions of inverted complementarity (inverted
      repeats), a structural motif previously reported for members of the genus
      Phytoreovirus. Genomic segment S6 was completely sequenced and found to consist
      of 2193 base pairs. Computer analysis indicated that the coding strand contained
      two large nonoverlapping open reading frames consisting of 363 and 310 codons and
      located in the 5'- and 3'-terminal domains, respectively. This was confirmed by
      cell-free translation studies with synthetic transcripts and denatured genomic
      RNA. However, only the product of the 5'-proximal open reading frame, a 40-kDa
      polypeptide, was efficiently expressed in vitro from the full-length S6 coding
      strand. This represents the first case in which a reovirus genomic segment was
      found to contain two large open reading frames in a nonoverlapping configuration,
      suggesting possible alternative strategies for regulation of gene expression by
      members of this genus. The combined results provide a molecular confirmation of
      the current classification scheme for plant-infecting reoviruses. Furthermore,
      the fact that the same terminal structural motif is conserved across genera
      provides additional evidence that these elements serve an important functional
      role during genome transcription or replication.

PMID- 1989383
TI  - Moloney murine leukemia virus IN protein from disrupted virions binds and
      specifically cleaves its target sequence in vitro.
AB  - The integration of retroviral DNA plays an essential role in the viral life
      cycle. Previous studies of the Moloney murine leukemia virus (M-MuLV) have shown
      that viral integration is mediated by the integrase (IN) protein acting on the 13
      bp inverted repeats that flank the linear viral DNA produced during reverse
      transcription. Prior studies have also shown that when the M-MuLV IN protein is
      produced in Escherichia coli it retains an ability to specifically associate with
      the viral inverted repeats (Krogstad and Champoux, 1990). In this study we
      present evidence that the IN protein present in detergent-disrupted virions is
      capable of specifically interacting with double-stranded oligonucleotides that
      correspond to the viral inverted repeats, and that this interaction may change
      after integration-related processing of the viral att sites. We further present
      evidence that, in vitro, detergent-disrupted virions are capable of specifically
      cleaving ds-IR oligonucleotides in an IN-dependent reaction that mimics the
      trimming step that precedes integration.

PMID- 1989384
TI  - Sequence analysis of the S RNA of the African arenavirus Mopeia: an unusual
      secondary structure feature in the intergenic region.
AB  - Mopeia virus is an apparently nonpathogenic African arenavirus which can protect
      animals from subsequent challenge by the closely related Lassa virus. As a step
      toward understanding these differences in pathogenicity and the means by which
      Mopeia virus infection can protect against subsequent Lassa virus infection, cDNA
      clones corresponding to 3419 nucleotides of Mopeia virus S RNA were isolated and
      sequenced. Two open reading frames, encoding the glycoprotein precursor (GPC) and
      nucleocapsid (N) proteins, were located in the ambisense arrangement
      characteristic of the arenaviruses. Comparison of the amino acid sequences of the
      translation products with those of two Lassa virus strains showed considerable
      conservation, with 74 and 80% identity for the two glycoproteins G1 and G2, and
      74% identity for the N protein. The putative dibasic site of GPC cleavage (R-R)
      was conserved, as were the potential N-linked glycosylation sites. A striking
      difference between Mopeia virus and Lassa virus was identified in the noncoding
      intergenic region. Instead of the single hairpin structure formed by base-pairing
      of complementary sequences which is usually found, the Mopeia virus S RNA has the
      potential to form two hairpins. These hairpins were similar in sequence and may
      have been formed in a duplication event during RNA replication. The possible
      contribution of this secondary structure feature to differences in pathogenicity
      between Mopeia and Lassa viruses is discussed.

PMID- 1989386
TI  - Structural characteristics of the M2 protein of influenza A viruses: evidence
      that it forms a tetrameric channel.
AB  - The evidence presented shows that the M2 protein of influenza A viruses exists in
      infected cells as a homotetramer composed of two disulfide-linked dimers held
      together by noncovalent interactions. The amphiphilic nature of the transmembrane
      alpha-helical domain is consistent with the protein forming a transmembrane
      channel with which amantadine, the specific anti-influenza A drug, interacts.
      Together these features provide a structural basis for the hypothesis that M2 has
      a proton translocation function capable of regulating the pH of vesicles of the
      trans-Golgi network, a role important in promoting the correct maturation of the
      hemagglutinin glycoprotein.

PMID- 1989385
TI  - HIV-1 V3 domain variation in brain and spleen of children with AIDS: tissue
      specific evolution within host-determined quasispecies.
AB  - DNA coding for the principal neutralization epitope of HIV-1 (the V3 domain of
      the envelope glycoprotein gp120) was amplified by polymerase chain reaction from
      postmortem brain and spleen tissue of three perinatally infected children who
      died of AIDS with progressive encephalopathy. Sequences obtained directly
      (without cloning) from this DNA were compared with sequences of 52 molecular
      clones made from this DNA. Cluster analysis showed that V3 domain sequences from
      two of the three children were similar to sequences from the American MN/SC
      isolates, while those from one child were more closely similar to the Caribbean
      RF isolate. Comparison of sequences obtained directly with consensus sequences
      derived from cloned DNA showed that V3 sequences are characteristic for an
      individual host. In one child, the V3 sequence determined directly from brain DNA
      was very distant from the consensus brain clone sequence and from the spleen
      sequences, suggesting a diverging quasispecies distribution. Site-directed
      hybridization demonstrated that brain-specific sequences present in 33% of brain
      derived clones were absent from clones derived from spleen. The evidence suggests
      that brain- and spleen-specific variants evolve independently within each host
      delimited quasispecies.

PMID- 1989387
TI  - Vaccinia virus DNA ligase is nonessential for virus replication: recovery of
      plasmids from virus-infected cells.
AB  - The essentiality of the vaccinia virus DNA ligase gene, SalF 15R, for virus
      growth was tested by insertional mutagenesis. A plasmid containing E. coli gpt
      inserted within a large deletion in the DNA ligase gene was transfected into
      vaccinia virus-infected cells and recombinant viruses selected by three cycles of
      plaque purification in the presence of mycophenolic acid (MPA). Surprisingly, in
      some isolates, which replicated in a manner indistinguishable from wild type (WT)
      virus, the WT gene was replaced by the gpt allele, demonstrating that the DNA
      ligase gene is nonessential for growth in cultured cells. In other isolates the
      entire plasmid was integrated into the virus genome by a single crossover event
      and a functional copy of the DNA ligase was retained. Southern blot analyses of
      the latter, drug-resistant viruses indicated extra DNA fragments, of sizes
      inconsistent with predicted viral structures, which represent the plasmid
      products of homologous recombination. Hirt extracts from cells infected with such
      multiply plaque purified virus isolates yielded plasmids that produced ampicillin
      resistant colonies after transformation of E. coli. These plasmids were of two
      structures, representing either the original plasmid used for transfection, or a
      plasmid containing the WT ligase gene rescued by recombination with the virus
      genome. Similarly, insertional mutagenesis of the vaccinia virus thymidine kinase
      (TK) gene with gpt yielded plasmids containing mutant or wild type TK alleles
      when recombinant viruses were selected in MPA. Such plasmids were not isolated
      when TK minus viruses were selected in 5-bromodeoxyuridine (BUdR).

PMID- 1989388
TI  - Dissection of functional domains of the packaging protein of bacteriophage T3 by
      site-directed mutagenesis.
AB  - Intracellular phage T3 DNA is synthesized as a concatemer in which unit-length
      molecules are joined together in head-to-tail fashion through terminally
      redundant sequences. During packaging of DNA, mature monomers are cut from the
      concatemer. The cutting is obligatorily coupled to DNA packaging. The packaging
      of phage DNA is under the control of a pair of noncapsid proteins, called
      packaging proteins, gp 18 and gp19. gp19 is an ATP-binding protein that plays
      multiple roles in DNA packaging. gp19 is predicted, from the sequence of its
      gene, to contain 586 amino acids, and has consensus sequences for an ATP binding
      site. To dissect structure-function relationships of gp19, mutations were
      introduced into the ATP binding domain and the mutant proteins were overproduced,
      purified and characterized. Mutant gp19 with a Gly-to-Asp mutation at amino acid
      61 (gp19 G61D) was defective in DNA packaging due to an altered interaction with
      ATP. Gp19 G424E, with a change in another putative ATP binding domain, was active
      in DNA packaging but was defective in DNA cutting. A second mutation in the
      latter domain, gp19 K430T, and a mutation at 553 (to give gp19 H553L), within a
      putative Mg2+ binding domain, had only minor effects on gp19 activities.

PMID- 1989389
TI  - Avian cells expressing the murine Mx1 protein are resistant to influenza virus
      infection.
AB  - The cDNA encoding the murine Mx1 protein, a mediator of resistance to influenza
      virus, was inserted into a replication-competent avian retroviral vector in
      either the sense (referred to as Mx+) or the antisense (referred to as Mx-)
      orientation relative to the viral structural genes. Both vectors produced virus
      retaining the Mx insert (Mx recombinant viruses referred to as Mx+ and Mx-)
      following transfection into chicken embryo fibroblasts (CEF). Mx protein of the
      appropriate size and nuclear localization was expressed only in CEF cells
      infected with the Mx+ virus. Mx expression was observed in all Mx(+)-infected
      cells and was stable during long-term culture. Cells infected with the Mx+ virus
      were resistant to infection by human influenza A/WSN/33 (H1N1) and avian
      influenza viruses A/Turkey/Wisconsin/68 (H5N9) and A/Turkey/Massachusetts/65
      (H6N2), but were susceptible to infection by the enveloped RNA viruses Sindbis
      and vesicular stomatitis virus (VSV). Normal CEF and cells infected with the Mx
      virus were susceptible to influenza A, Sindbis, and VSV. The synthesis of
      influenza proteins, especially the larger polymerase and hemagglutinin proteins,
      was reduced in Mx+ retrovirus-infected cells superinfected by influenza A.

PMID- 1989390
TI  - The termini of the chlorella virus PBCV-1 genome are identical 2.2-kbp inverted
      repeats.
AB  - The Chlorella virus PBCV-1 genome is a linear nonpermuted 333-kbp dsDNA molecule
      with covalently closed hairpin termini. The termini (minus the hairpin) are
      identical inverted repeats of at least 2185 bases after which the sequence
      diverges. The inverted repeats contain two small potential open reading frames
      and several direct repeats. However, neither the open reading frames nor the
      remainder of the inverted repeats are transcribed during PBCV-1 replication.
      Twenty-nine other Chlorella virus DNAs, of 36 tested, hybridized to the PBCV-1
      terminal fragments.

PMID- 1989391
TI  - Cleavage and purification of prokaryotically expressed HIV gag and env fusion
      proteins for detection of HIV antibodies in the ELISA.
AB  - Parts of the gag p24 and the gp41 transmembrane protein of the human
      immunodeficiency virus HIV-1 were expressed as fusion proteins in Escherichia
      coli, using an expression vector carrying aa 1-375 of the lac-Z gene linked to
      the recognition sequence for the blood coagulation factor Xa. Fusion proteins
      were cleaved into the bacterial and viral portion and the viral polypeptide was
      purified by a molecular sieve column. The purified viral antigens were tested
      with 288 human sera in the enzyme-linked immunosorbent assay (ELISA) technique.
      Comparison with commercially available tests showed comparable sensitivity and a
      higher specificity of the gag/env-ELISA for borderline reactive sera.

PMID- 1989392
TI  - Characterization of recombinant helper retroviruses from Moloney-based vectors in
      ecotropic and amphotropic packaging cell lines.
AB  - We have characterized the recombinant replication-competent retrovirus (RCV)
      arising from p delta N2-derived vectors in the packaging cell lines psi 2
      (ecotropic) and PA317 (amphotropic). Detailed restriction patterns and sequence
      of the envelope region of these RCVs has indicated that they arose from
      recombination events between the virus plasmids used to create the packaging cell
      line and the vectors. There was no evidence of recombination involving endogenous
      murine retroviral sequences in the packaging cell line or in transduced
      hematopoietic cells. In addition, we have confirmed that the mutation of the
      start codon of the pXM5(N2) derivatives gag+ sequence drastically decreased the
      occurrence of RCV production. These results offer encouragement that the risk of
      RCV production can be adequately decreased in gene therapy applications of
      defective retrovirus vectors.

PMID- 1989393
TI  - Reduction in CD4 binding affinity associated with removal of a single
      glycosylation site in the external glycoprotein of HIV-2.
AB  - The role of selected glycosylation sites in the ability of the envelope
      glycoprotein of HIV-2 (gp 105) to bind to CD4 has been investigated. Loss of
      glycosylation sites at amino acids 410 and 447 did not affect the CD4 binding
      ability of gp 105 even when removed in pair combination. Loss of a single
      glycosylation site at amino acid 400, however, was sufficient to cause a
      reduction of at least 50-fold in the efficiency of receptor binding. These data
      support the hypothesis that some of the carbohydrate side chains on gp 105 have a
      profound effect on biological activity.

PMID- 1989394
TI  - Characterization of preearly genes in the terminal repetition of bacteriophage
      BF23 DNA by nucleotide sequencing and restriction mapping.

PMID- 1989395
TI  - 1991 75th Anniversary AARN. Our history--a proud heritage 1960-64.

PMID- 1989396
TI  - Interview with the President. Interview by Arlene Johnston.

PMID- 1989397
TI  - Specialization in nursing: the need for nurses to be sexuality specialists.

PMID- 1989398
TI  - Nursing consultant--education: responsibilities and activities.

PMID- 1989399
TI  - Is the VON still around?

PMID- 1989400
TI  - Nursing and mental health: taking care of ourselves.

PMID- 1989401
TI  - Hypertension and ischemic heart disease: the challenge of the 1990s.

PMID- 1989402
TI  - Improving compliance and increasing control of hypertension: needs of special
      hypertensive populations.
AB  - Approximately 60 million people in the United States have hypertension. More than
      half are either untreated or treated without blood pressure control, despite the
      well-known risks of hypertension and the established benefits of treatment. The
      major reason for inadequate control of hypertension is poor adherence to
      treatment. Approximately 50% of patients with hypertension fail to keep follow-up
      appointments, and only 60% take their medications as prescribed. Barriers to
      effective therapeutic adherence include poor doctor-patient communication, cost
      of antihypertensive therapy, and side effects of the drugs. To increase control
      of hypertension, compliance with therapy must be improved. Physicians and
      patients must be mutually committed to achieving control of blood pressure.
      Physicians should communicate instructions clearly and prescribe therapies that
      are effective, affordable, and have minimal or no adverse effects on patient
      quality of life or overall cardiac risk profile. The needs of special
      hypertensive populations (i.e., elderly, black, and young patients) must also be
      recognized and addressed. Patients must follow recommendations and alert their
      physicians to any problems with their medications--particularly those relating to
      side effects and cost. When selecting drug therapy it should be noted that older
      patients are sensitive to volume depletion and sympathetic inhibition. In this
      group of patients, initial drug doses should be low and increments smaller and
      more gradual than in younger patients. Black patients with hypertension show an
      accentuated response to diuretics and blunted responses to beta-blockers and
      angiotensin-converting enzyme (ACE) inhibitors as monotherapy. However, when used
      with a diuretic, there are no racial differences in the blood pressure lowering
      effects of beta-blockers and ACE inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1989403
TI  - Managing the whole patient with hypertension: practical applications in a
      clinical setting.
AB  - Physicians are aware of the value of treating hypertension. Complications such as
      stroke and congestive heart failure are less likely to occur in the well
      controlled patient. In our quest to add coronary heart disease to this list, we
      must go beyond simple reduction of blood pressure. We must consider other risk
      factors such as hypercholesterolemia, cigarette smoking, diabetes mellitus, and
      family history. The presence of one or more of these may indicate a more
      aggressive treatment approach. Similarly the presence of left ventricular
      hypertrophy, coronary disease, or renal disease may indicate specific
      pharmacotherapy. On the other hand, the low-risk patient with no other problems
      or conditions may be treated with only nonpharmacologic therapy such as weight
      loss, dietary sodium reduction, and/or alcohol restriction. Every patient has a
      different constellation of findings. Every patient should be treated
      individually. It is no longer sufficient just to lower blood pressure; we need to
      manage the whole patient with hypertension; keeping in mind that most
      antihypertensive agents are equally effective, the side effect profile is often
      the decisive factor in choosing an antihypertensive agent.

PMID- 1989404
TI  - Federal funding for nutrition research and training.

PMID- 1989405
TI  - Discovery of human zinc deficiency and studies in an experimental human model.
AB  - The importance of zinc for human health was first documented in 1963. During the
      past 25 y, deficiency of zinc in humans due to nutritional factors and several
      disease states has now been recognized. The high phytate content of cereal
      proteins is known to decrease the availability of zinc, thus the prevalence of
      zinc deficiency is likely to be high in a population consuming large quantities
      of cereal proteins. Alcoholism, malabsorption, sickle cell anemia, chronic renal
      disease, and chronically debilitating diseases are now known to be predisposing
      factors for zinc deficiency. A spectrum of clinical manifestations ranging from
      mild to severe degree have now been recognized in human zinc-deficiency states.
      Zinc is required for many biological functions including DNA synthesis, cell
      division, and gene expression. It is required for the activity of many enzymes in
      biological systems. Recent studies indicate that zinc is needed for cell-mediated
      immunity.

PMID- 1989407
TI  - Body composition by bioelectrical-impedance analysis compared with deuterium
      dilution and skinfold anthropometry in patients with chronic obstructive
      pulmonary disease.
AB  - Body composition is an important measure of nutritional status in patients with
      chronic obstructive pulmonary disease (COPD). We generated a regression model for
      bioelectrical impedance (BI) by using deuterium dilution (2H2O) as a reference
      method in 32 COPD patients, aged 63 +/- 9 y (mean +/- SD), in stable pulmonary
      and cardiac condition. Height squared divided by resistance (Ht2/Res) correlated
      well with total body water (TBW) as measured by 2H2O (r = 0.93, P less than
      0.001, SEE = 1.9 L). The best-fitting regression equation to predict TBW
      comprised Ht2/Res and body weight (r2 = 0.89, SEE = 1.8 L, P less than 0.001). BI
      predicted TBW was used to estimate BI-fat-free mass (FFM) that was compared with
      skinfold-thickness-based FFM predictions (Anthr-FFM). Relative to BI-FFM a
      significant overestimation of 4.4 +/- 0.8 kg was found by Anthr-FFM. Our results
      suggest that BI is a useful measure of body composition in patients with severe
      COPD.

PMID- 1989406
TI  - 1990 Atwater lecture. The science and the practice of nutrition: reflections and
      directions.

PMID- 1989408
TI  - Further evidence for the presence of "small eaters" and "large eaters" among
      women.
AB  - One hundred thirty-four women, aged 36 +/- 4 (mean +/- SD) y, BMI 20 +/- 3 kg/m2,
      perceiving themselves as having either a low or high energy intake (EI),
      participated in a study to determine variations in EI. Information on EI and
      activity level was obtained from repeated 7-d records. The 40 subjects with the
      lowest EI (in kcal/kg body wt) were categorized as small eaters (SEs); the 40
      subjects with the highest EI were considered to be large eaters (LEs). The
      absolute (in kcal) and relative (in kcal/kg body wt) EIs of the SE and LE groups
      were 1488 +/- 312 and 27 +/- 4 for the SE group, respectively and 2393 +/- 509
      and 47 +/- 6 for the LE group, respectively. There was no significant difference
      in activity level or fat-free mass (FFM) between the groups. However, LEs weighed
      significantly less (51 vs 55 kg) and were leaner (22% body fat vs 33%) than were
      SEs. Individuals with similar FFM and activity level can vary significantly in EI
      needs.

PMID- 1989409
TI  - Energy-intake restriction and diet-composition effects on energy expenditure in
      men.
AB  - Eight men were fed at maintenance for 2 wk, followed by 4 wk at 50% of
      maintenance, then 1 wk at maintenance. The diets were formulated to contain
      either 40% or 20% of energy from fat. Daily energy expenditure (24-h EE) was
      determined by indirect calorimetry at the end of the 2-wk maintenance period; on
      days 1, 7, and 28 of reduced energy intake; and on days 1 and 7 of refeeding.
      During the reduced-energy period, body weight decreased from 96.6 to 91.5 kg and
      body fat decreased from 30.4% to 27.7%. There were no significant differences in
      24-h EE or energy requirements per unit body weight due to diet composition or
      weight loss. Maintenance metabolizable-energy (ME) requirement averaged 31.0
      kcal/kg body wt. Overall, the efficiency of ME use relative to body stores was
      0.87 and was greater for high-fat than for low-fat diets. There was some evidence
      of an increase in the efficiency of energy use of body stores after weight loss.
      Substrate use reflected diet composition and energy-balance status independent of
      changes in body composition.

PMID- 1989410
TI  - Resting energy expenditure is increased in stable, malnourished HIV-infected
      patients.
AB  - Resting energy expenditure (REE) was measured by reference to body composition in
      50 malnourished patients with human immunodeficiency virus (HIV) infection and
      compared with that of 14 healthy subjects. Among HIV patients, 40 had acquired
      immune deficiency syndrome (AIDS) and 10 had AIDS-related complex (ARC). All were
      in stable condition and had a previous history of progressive wasting, ie, a mean
      body weight loss of 14.2 +/- 8.1 kg over 16.6 mo (range 2-49 ms). The mean REE
      was 14% higher than estimated basal energy expenditure (EBEE), according to the
      Harris and Benedict formula. Thirty-four patients (68%) were classified as
      hypermetabolic (REE greater than 110% EBEE). The best predictable variable for
      REE was fat-free mass (FFM), as determined by an anthropometric method (r = 0.72;
      P less than 0.001). The mean REE was 12% higher in HIV patients than in the
      control group FFM (156 +/- 19 vs 124 +/- 17 kJ.kg FFM-1.d-1). We concluded that
      in stable and malnourished HIV patients, the progressive wasting may be partly
      related to an increase in REE. The mechanism of this hypermetabolic state remains
      to be established.

PMID- 1989411
TI  - Menstrual-cycle patterns in energy and macronutrient intake.
AB  - For 14 subjects drawn from the Beltsville One-Year Dietary Intake Study, patterns
      of energy, protein, fat, carbohydrate, protein/1000 kcal, fat/1000 kcal, and
      carbohydrate/1000 kcal were examined across pre- and postmenstrual periods.
      Individual subjects contributed data for one to four menstrual periods. Energy,
      fat, and fat/1000 kcal intakes were significantly higher in the 10 premenstrual
      days than in the 10 postmenstrual days. After elimination of effects attributable
      to between-subject differences and to balance periods included in the Beltsville
      study, fitted sine curves explained 14% and 25% of the variance in energy and fat
      intakes, respectively, across 14 premenstrual and 14 postmenstrual days, and 20%
      of the variance in fat/1000 kcal. Independent patterns were identified in
      absolute and relative protein intake. No patterns were discerned for
      carbohydrate. Physiological or behavioral factors appear to influence both total
      food intake (energy intake) and food selection (macronutrients/1000 kcal) across
      the menstrual cycle.

PMID- 1989412
TI  - Detoxification and mineral supplementation as functions of geophagy.
AB  - Clays employed historically in the consumption of astringent acorns plus seven
      edible clays from Africa were examined in relation to the functional significance
      of human geophagy. On the basis of sorptive maxima for tannic acid ranging from
      5.6 to 23.7 mg/g, we conclude that adsorption of tannic acid in traditional acorn
      preparation methods in California and Sardinia helped make these nuts palatable.
      Calcium available in solution at pH 2.0 and 0.1 mol NaCl/L was 2.10 and 0.71 mg/g
      for the Sardinian and Californian clays, respectively. The African clays released
      calcium, copper, iron, magnesium, manganese, or zinc in amounts of nutritional
      significance from some clays but not from others. A clay recovered from an
      archaeological site occupied by Homo erectus and early H. sapiens was
      indistinguishable mineralogically, in detoxification capacity and in available
      minerals, from clays used in Africa today. We suggest that the physiological
      significance of geophagy made it important in the evolution of human dietary
      behavior.

PMID- 1989413
TI  - Determinants of energy, protein, lipid, and lactose concentrations in human milk
      during the first 12 mo of lactation: the DARLING Study.
AB  - Factors associated with concentrations of energy-yielding nutrients in human milk
      were examined at 3, 6, 9, and 12 mo postpartum in the DARLING (Davis Area
      Research on Lactation, Infant Nutrition and Growth) Study. Samples were obtained
      by complete expression of alternate breasts over 24 h. Milk energy density was
      highly correlated with lipid concentration; both were positively related to
      maternal percent of ideal body weight (%IBW) at 6, 9, and 12 mo and negatively
      related to milk volume at 3 mo and to parity at 12 mo. Milk protein concentration
      was negatively related to milk volume at 6 and 9 mo and positively related to
      nursing frequency at 6 mo and %IBW at 9 mo. Milk lactose concentration was
      positively related to milk volume at 6 and 9 mo and to continued amenorrhea at 9
      mo. In a subsample who completed dietary records, protein intake was positively
      associated with lipid concentration after 16 wk postpartum but not before. These
      findings suggest that milk composition is more sensitive to maternal factors such
      as body composition, diet, and parity during later lactation than during the
      first few months.

PMID- 1989415
TI  - Correlation of isomeric fatty acids in human adipose tissue with clinical risk
      factors for cardiovascular disease.
AB  - The relationships between the adipose tissue concentrations of 19 geometric and
      positional fatty acid isomers and 10 cardiovascular disease risk factors were
      determined in 76 free-living adult males. The percentages for trans isomers
      (total mean +/- SD 4.14 +/- 0.97%) and cis isomers (total mean +/- SD 2.91 +/-
      0.34%) in adipose tissue generally agreed with dietary estimates based on the
      consumption of hydrogenated oils. A major exception was the percentage of 11c
      18:1, which was twofold higher in adipose tissue. The total level of fatty acid
      isomers in adipose tissue or a factor (derived by factor analysis) that was
      representative of isomers of dietary origin was not significantly correlated with
      the cardiovascular risk factors. Only three trans isomers (11t-18:1, 12t-18:1,
      and 5t-14:1) and three cis isomers (11c-18:1, 13c-18:1, and 7c-16:1) were weakly
      correlated either positively or negatively with age, body mass index, plasma and
      lipoprotein cholesterol, and/or blood pressure (P less than 0.05, r greater than
      0.231).

PMID- 1989414
TI  - Adipose tissue fatty acid composition and its relations to diet and plasma lipid
      concentrations in hemodialysis patients.
AB  - Adipose tissue fatty acid composition, serum lipid profile, and dietary intake of
      37 patients on maintenance hemodialysis were studied. In August 1982, 1984, and
      1986, analyses were carried out in 15 normotriglyceridemic (NTG) and 22
      hypertriglyceridemic (HTG; type IV hyperlipidemia) patients. No correlations were
      found between dietary intake of polyunsaturated fatty acids (PUFAs), ratio of
      polyunsaturated to saturated fatty acids (P-S ratio), and carbohydrate content on
      the one hand and serum lipid concentrations on the other in the two groups.
      Adipose tissue linolenic acid correlated negatively with serum cholesterol in
      both groups. Strong correlations were found between dietary intake of PUFAs and
      adipose tissue linoleic acid content, between PUFAs and the double-bond index,
      between P-S ratio and adipose tissue linoleic acid content, and between P-S ratio
      and the double-bond index. No significant differences in dietary intake or
      adipose tissue fatty acid composition were observed between NTG and HTG patients.
      Thus, no evidence was found for exogenous dietary influences on serum lipid
      concentrations. The adipose tissue linoleic acid content did reflect the dietary
      intake of PUFAs.

PMID- 1989416
TI  - Retina fatty acid composition of piglets fed from birth with a linoleic acid-rich
      vegetable-oil formula for infants.
AB  - The effects of a vegetable-oil-based formula containing 30% 18:2n-6 (18:2 omega
      6), 0.8% 18:3n-3, and no n-6 or n-3 long-chain polyunsaturated fatty acids (LCPs)
      on retina total lipid, ethanolamine phosphoglyceride (EPG), and
      phosphatidylcholine (PC) fatty acid composition were studied in neonatal piglets.
      Term-gestation piglets were fed sow milk (SMF) or the formula (FF) from birth for
      5, 10, 15, or 25 d. After 25 d feeding, the 22:6n-3 was reduced by 24% in total
      lipid, 20% in EPG, and 28% in PC of retinas of FF relative to SMF piglets. A
      compensatory increase in 22:4n-6 and 22:5n-6 concentrations occurred in retina
      total lipid, EPG, and PC of FF animals. The data suggest that the exclusive
      feeding of formulas devoid of LCPs and high in 18:2n-6 and/or 18:2n-6 and 18:3n-3
      compromises normal accretion of 22:6n-3 in neonatal piglet retina. The potential
      reversibility of these changes or their effects on vision are not known.

PMID- 1989417
TI  - Essential fatty acid sufficiency does not preclude fat-soluble-vitamin deficiency
      in short-bowel syndrome.
AB  - Patients with extensive small-bowel resection may experience malabsorption and
      nutrient deficiencies. We evaluated the ability to absorb fat and fat-soluble
      vitamins in a short-gut patient. For 18 wk after stopping intravenous lipid,
      while consuming a low-lactose, low-fat diet, he exhibited no clinical
      manifestations of essential fatty acid deficiency (EFAD). Serum 20:4n-6 (20:4
      omega-6) and 18:2n-6 fatty acid concentrations were normal, whereas the
      concentration of 20:3n-9 remained less than or equal to 0.1% of total serum fatty
      acids. Although serum vitamin A was normal, beta-carotene was undetectable
      despite oral supplementation. Prothrombin time was elevated until parenteral
      vitamin K was given. This patient has fat absorption adequate to prevent EFAD but
      inadequate absorption of fat-soluble vitamins. In patients with short bowel, the
      requirements for parenteral lipids and fat-soluble vitamins should be determined
      independently.

PMID- 1989418
TI  - Nitrogen deposition in malnourished children with cystic fibrosis.
AB  - To determine the protein nutritional status of 21 malnourished children with
      cystic fibrosis (CF), total body nitrogen (TBN) was measured and the results were
      compared with 21 control subjects. CF patients demonstrated a lower TBN (P less
      than 0.001). When matched for height (n = 10) or bone age (n = 13), the CF
      patients still had a depressed TBN/height or TBN/lean body mass (P less than
      0.05). To assess nitrogen deposition during nutritional rehabilitation, repeat
      TBN measurements were performed on the 21 CF patients. Nitrogen deposition ranged
      from -230 to 550 g/y and correlated with weight velocity (r = 0.78, P less than
      0.001). Increased nitrogen deposition (greater than 150 g/y) was generally
      associated with normal height gain (height velocity SD score greater than -2.00)
      and weight gain (greater than 2.0 kg/y). Decreased nitrogen deposition was
      associated with poor weight gain but did not preclude normal linear growth. These
      data suggest an important role for TBN estimations in defining protein
      nutritional status in children and indicate that skeletal growth can continue in
      the presence of minimal nitrogen deposition.

PMID- 1989419
TI  - Plasma lecithin-cholesterol acyltransferase activity and plasma lipoprotein
      composition and concentrations in kwashiorkor.
AB  - Plasma lecithin-cholesterol acyltransferase (LCAT) activity, lipoprotein
      composition, and lipoprotein concentrations were measured in 21 children with
      kwashiorkor before (day 1), during (day 10), and after treatment (day 30). Day 1
      LCAT activity (78.2 mumol.L-1.h-1) was decreased with respect to day 10 (139.2
      mumol.L-1.h-1, P less than 0.001) and day 30 (108.0 mumol.L-1.h-1, P = 0.08).
      Plasma total cholesterol (TC), cholesterol ester (CE), and lipoprotein CEs (VLDL,
      IDL, LDL, and HDL) were reduced relative to days 10 and 30 (P less than 0.001).
      Before treatment HDL composition was abnormal. On days 1, 10, and 30, the
      respective mean HDL-apolipoprotein A-I (apo A-I) concentrations were 23.33,
      39.66, and 36.08 mumol/L. LDL-apo B concentrations were 0.40, 0.68, and 0.56
      mumol/L (P less than 0.01, days 10 and 30 vs day 1). LDL particles on day 1 were
      decreased in number, depleted of CE, and laden with triacylglycerol and surface
      lipids. LCAT activity on day 1 correlated with LDL-CE linoleate (P less than
      0.05, r = 0.48). Reduced plasma LCAT activity is an important factor related to
      abnormalities in lipoprotein composition and concentrations.

PMID- 1989420
TI  - Preprandial blood glucose values and glycemic responses in insulin-dependent
      diabetes mellitus at constant insulinemia.
AB  - The influence of preprandial blood glucose (PPBG) concentration on glycemic
      responses was studied in seven subjects with insulin-dependent diabetes who, by
      means of the artificial pancreas, had achieved PPBG concentrations of 6, 9, and
      17 mmol/L. A test meal of 50 g parboiled rice was given at the three different
      occasions and a constant insulin infusion was provided during the observation
      periods. The mean postprandial-blood-glucose-response area (above basal) differed
      significantly at the three blood glucose concentrations of 6, 9, and 17 mmol/L,
      reaching 1371, 621, and 179 mmol/L x 240 min, respectively (P less than 0.01). A
      negative correlation between the PPBG concentrations and the glycemic responses
      to the test meal was found (r = 0.94; P less than 0.001). The fasting insulin
      concentration at a PPBG concentration of 17 mmol/L was lower than at a PPBG
      concentration of 6 and 9 mmol/L. In conclusion, the glycemic responses to a
      carbohydrate meal are inversely correlated to the PPBG concentration in insulin
      dependent diabetic subjects.

PMID- 1989421
TI  - Vitamin B-12 status in a macrobiotic community.
AB  - Vitamin B-12 status was assessed in a group of 110 adults and 42 children from a
      macrobiotic community in New England. Dietary and anthropometric information also
      was obtained. Fifty-one percent of the adults had low concentrations of serum
      vitamin B-12, which inversely correlated with duration of macrobiotic diet
      practice. Urinary methylmalonic acid (MMA) excretion was inversely correlated
      with serum vitamin B-12, and 30% of adults sampled had high urinary MMA. Fifty
      five percent of children had high urinary MMA, and MMA was higher in the group
      that consumed a macrobiotic diet during their entire lifetime. Children were
      relatively short in stature and weight, and decreased stature was associated with
      high urinary MMA. In both adults and children vitamin B-12 status was better with
      more consumption of dairy products or with higher tertile of reported frequencies
      of vitamin B-12 consumption of various animal products. Vitamin B-12 status
      appeared to be unrelated to consumption of several vegetarian foods.

PMID- 1989422
TI  - Age-dependent changes in thiamin concentrations in whole blood and cerebrospinal
      fluid in infants and children.
AB  - We determined pediatric age-specific normative ranges for total, phosphorylated,
      and nonphosphorylated thiamin in whole blood (n = 323) and cerebrospinal fluid
      (CSF; n = 208). Whole-blood total thiamin decreased from 258 +/- 63 (mean +/- SD;
      age 0-3 mo group) to 214 +/- 44 nmol/L (age 3-12 mo group) in the first year of
      life and was stable at 187 +/- 39 nmol/L after 12 mo of age. The overall decline
      in whole-blood total thiamin was mainly due to a drop in phosphorylated thiamin,
      the biologically active form. Mean CSF total thiamin decreased from 135 +/- 42
      (age 0-9-mo group) to 107 +/- 34 nmol/L (age 9-18-mo group) in the first 1.5 y of
      life and was stable at 84 +/- 51 nmol/L thereafter. This overall decline was due
      initially to a drop in nonphosphorylated thiamin and later to a drop in
      phosphorylated thiamin. The changes in whole blood and CSF occurred independently
      and probably represent metabolic and neurological maturation of the infant. Whole
      blood total and phosphorylated thiamin concentrations were lower in blacks only
      after pubarche. Age-specific norms should be used for determining the thiamin
      status in infancy because thiamin concentrations are significantly higher in the
      first few months of life.

PMID- 1989423
TI  - Ascorbic acid prevents the dose-dependent inhibitory effects of polyphenols and
      phytates on nonheme-iron absorption.
AB  - The effects of maize-bran phytate and of a polyphenol (tannic acid) on iron
      absorption from a white-bread meal were tested in 199 subjects. The phytate
      content was varied by adding different concentrations of phytate-free and
      ordinary maize bran. Iron absorption decreased progressively when maize bran
      containing increasing amounts of phytate phosphorous (phytate P) (from 10 to 58
      mg) was given. The inhibitory effect was overcome by 30 mg ascorbic acid. The
      inhibitory effects of tannic acid (from 12 to 55 mg) were also dose dependent.
      Studies suggested that greater than or equal to 50 mg ascorbic acid would be
      required to overcome the inhibitory effects on iron absorption of any meal
      containing greater than 100 mg tannic acid. Our findings indicate that it may be
      possible to predict the bioavailability of iron in a diet if due account is taken
      of the relative content in the diet of the major promoters and inhibitors of iron
      absorption.

PMID- 1989424
TI  - Dietary calcium and iron: effects on blood pressure and hematocrit in young
      spontaneously hypertensive rats.
AB  - Supplemental dietary calcium in spontaneously hypertensive rats (SHRs) aged 21-28
      d produces a decrease in blood pressure and hematocrit. The simultaneous fall in
      hematocrit and blood pressure suggests that the changes in blood pressure may be,
      in part, a consequence of the decrease in hematocrit and reduction in viscosity.
      To examine this possibility, SHRs aged 21 d were placed on one of four diets
      varying in iron content. At age 28, the animals showed iron-induced variations in
      hematocrit (P less than 0.001) but no difference in blood pressure. Subsequent
      manipulation of the ratio of calcium and iron in the diets of additional groups
      of animals resulted in variations in hematocrit that were independent of the
      calcium-induced alterations in blood pressure. We conclude that the effects of
      calcium on blood pressure are relatively independent of its effects on
      hematocrit.

PMID- 1989425
TI  - Zinc absorption in women: comparison of intrinsic and extrinsic stable-isotope
      labels.
AB  - Fractional absorption of extrinsic and intrinsic zinc from milk-based formulated
      diets was measured in 10 young women by using a simultaneous triple-isotope
      method based on fecal monitoring of unabsorbed enriched stable-isotope labels.
      Zinc intake was held nearly constant (mean zinc intake = 1.48 mumol.kg body wt
      1.d-1) throughout the 18-d controlled feeding phase of the study by addition of
      extrinsic 64Zn to all formula feedings, with substitution of the extrinsic 67Zn
      label for some of the 64Zn when formula intrinsically labeled with 70Zn was
      given. Fractional absorption values of intrinsic and extrinsic zinc labels, 0.267
      +/- 0.092 (mean +/- SD) and 0.282 +/- 0.086, respectively, were highly correlated
      (r = 0.83, P less than 0.05) and did not differ significantly. The ratio of
      fractional absorption of the extrinsic to that of the intrinsic label, 1.08 +/-
      0.20 (mean +/- SD), was not significantly different from unity. The results show
      that extrinsic labeling by use of enriched stable isotopes is a valid means of
      determining zinc absorption from milk-based diets in adult humans.

PMID- 1989426
TI  - Dose-dependent inhibitory effect of phenolic compounds in foods on nonheme-iron
      absorption in men.
AB  - Nonheme-iron absorption from a typical Southeast Asian meal was studied to
      examine the effect of a common vegetable, Yod Kratin, which contains a
      considerable amount of iron-binding phenolic groups. Yod Kratin (leaves of the
      lead tree) is a very popular vegetable in Thailand. It is consumed at least once
      a week year round, sometimes every day, together with the main meal. With a
      common portion size of the vegetable (20 g), iron absorption was reduced by
      almost 90%. As little as 5 g inhibited iron absorption by 75%. Addition of
      ascorbic acid partly counteracted inhibition. Adding 100 mg ascorbic acid reduced
      inhibition of iron absorption from 5 g Yod Kratin by half and the inhibition from
      10 g Yod Kratin by a quarter. The study illustrates the marked effect of iron
      binding phenolic compounds on iron nutrition and, thus, the importance of
      acquiring knowledge of the content of such compounds in different foods.

PMID- 1989427
TI  - Blood pressure lowering in elderly subjects: a double-blind crossover study of
      omega-3 and omega-6 fatty acids.
AB  - In 46 elderly (aged greater than or equal to 60 y) hypertensive subjects with
      entry systolic blood pressure (SBP) greater than or equal to 160 or diastolic
      blood pressure (DBP) greater than or equal to 90 mm Hg, our specific aim in a
      randomized, double-blind, crossover study (two 8-wk treatment periods separated
      by a 3-wk washout) was to compare blood pressure-lowering effects of 9 g fish
      oil/d [omega-3 (n-3) fatty acid] vs 9 g corn oil/d [omega-6 (n-6) fatty acid].
      After a 4-wk baseline period, 22 subjects were randomly assigned to receive fish
      oil and 24 to receive corn oil. For both 8-wk treatments there were no between
      group differences in the change in blood pressure. There was a treatment
      difference for standing DBP when baseline values were compared with those after
      treatment 2; DBP decreased by 5.1 mm Hg in the fish-oil group vs 0.72 mm Hg in
      the corn-oil group (P = 0.024). Within groups during the first treatment, both
      fish oil and corn oil lowered all four blood pressure measures (P less than
      0.05); blood pressures were not further lowered during the second treatment
      compared with the washout period. There were no significant between-group
      differences in laboratory safety tests or categorical side effects. Fish oil
      lowered triglycerides by 0.47 mmol/L (P less than 0.001). In elderly subjects,
      diet plus both omega-3 and omega-6 supplements (9 g/d) safely and effectively
      lower SBP and DBP.

PMID- 1989428
TI  - Human requirements for riboflavin.

PMID- 1989429
TI  - Functional significance of mild-to-moderate malnutrition.

PMID- 1989430
TI  - The progression of panels.

PMID- 1989432
TI  - The diagnosis of mesothelioma by panels.

PMID- 1989431
TI  - The structure of expert diagnostic knowledge in occupational medicine.
AB  - Development of an artificial intelligence expert system for diagnosing
      occupational lung disease requires explicit specification of the structure of
      knowledge necessary in clinical occupational medicine independent of the process
      by which the knowledge is utilized. Furthermore, explicit recognition of sources
      of uncertainty is necessary. Seven categories of knowledge define the diagnostic
      knowledge base in occupational pulmonary medicine. These include four objects
      (jobs, industries, exposures, and diseases) and three relationships between pairs
      of objects. This analysis demonstrates some of the unique aspects of occupational
      medicine expertise.

PMID- 1989433
TI  - Pleural lesions and the ILO classification: the need for a revision.
AB  - The ILO system for radiographic classification of pneumoconioses is a very
      important epidemiological tool. Unfortunately, the classification is not precise
      for pleural lesions, which are especially important for evaluation of asbestos
      related diseases. The classification cannot separate extrapleural fat from
      diffuse thickening of the pleura, nor large plaques from diffuse thickening. In
      this paper, a short review of the different lesions are given and a revised
      scheme is suggested. This scheme includes as separate lesions: pleural fat;
      lesions of the parietal pleura, i.e., pleural plaques; and lesions of the
      visceral pleura, i.e., diffuse thickening and rounded atelectasis. The extent and
      width, as in the present ILO scheme, could be abolished.

PMID- 1989434
TI  - Mortality patterns among petroleum refinery and chemical plant workers.
AB  - A historical cohort study was conducted to evaluate the mortality experience of
      6,831 employees of the Shell Oil Company, Deer Park, Texas, petroleum refinery
      and chemical plant with emphasis on cancer mortality. Subjects were all workers
      with potential plant exposure who were employed for at least 3 months during 1948
      72. Vital status was determined as of 12/31/83 for 98% of the cohort and death
      certificates were obtained for 95.4% of 1,180 observed deaths. The statistical
      analyses excluded 159 female study members. For all causes of death combined, all
      cancers combined, and for most of the nonmalignant disease categories examined,
      there were deficits in mortality among refinery workers, chemical plant workers,
      and workers with experience in both areas. These deficits were generally most
      pronounced for chemical plant workers. An analysis of specific cancer sites
      revealed patterns of increased risk suggestive of a possible relationship between
      occupational exposures in the refinery and lympho-reticulosarcoma. Patterns of
      increased risk were also observed among chemical plant workers for a category of
      lymphopoietic tissue cancers, including multiple myeloma, myelofibrosis,
      polycythemia vera, and certain non-Hodgkin's lymphomas. Some very limited
      evidence of a possible workplace association was also found among refinery
      workers for leukemia and cancers of the central nervous system and biliary
      passages/liver. No evidence was found of an increased risk for cancer of the
      respiratory system or stomach or for malignant melanoma. A work history review of
      all suspect cancer excesses failed to identify any common work areas, job
      assignments, or exposure potentials, although the lack of detailed data on
      specific chemical exposures precluded accurate assessments of exposure-response.

PMID- 1989435
TI  - Implications of OSHA's reliance on TLVs in developing the air contaminants
      standard.
AB  - This paper evaluates the decision by the Occupational Safety and Health
      Administration (OSHA) to base its Air Contaminants Standard on the threshold
      limit values (TLVs) of the American Conference of Governmental Industrial
      Hygienists. Contrary to the claim made by OSHA in promulgating the standard, the
      TLV list was not the sole available basis for a generic standard covering toxic
      air contaminants. The National Institute for Occupational Safety and Health
      (NIOSH) presented data indicating that the TLVs were insufficiently protective
      for 98 substances. NIOSH Recommended Exposure Limits (RELs) were available for 59
      of these substances. The ratio of PEL to REL ranged up to 1,000, with a median of
      2.5 and a mean of 71.4. OSHA excluded 42 substances from the standard altogether
      despite the availability of NIOSH RELs, solely because no TLV had been
      established.

PMID- 1989436
TI  - Long-term mortality in miners with coal workers' pneumoconiosis in The
      Netherlands: a pilot study.
AB  - In order to investigate whether the prolonged exposure to coal mine dust
      increases the cancer risk for coal miners, a pilot study in a selected cohort of
      334 Dutch miners with coal workers' pneumoconiosis (CWP), followed from 1956
      until 1983, was conducted. In total, 165 miners had died (49.4%); for 162 (98.2%)
      the cause of death was traced. In comparison to the general Dutch male
      population, total mortality in the cohort was statistically significantly
      increased (SMR: 153). This was in general due to the significantly higher than
      expected cancer mortality (SMR: 163), cancer of stomach and small intestine (SMR:
      401) and nonmalignant respiratory disease (SMR: 426). The lung cancer mortality
      was within the expected range.

PMID- 1989437
TI  - Can exposure to electromagnetic radiation in diathermy operators be estimated
      from interview data? A pilot study.
AB  - As preparation for a case-control study dealing with possible teratogenic
      property of short waves, a pilot study was conducted in order to compare exposure
      assessment from different sources. In 11 physiotherapy clinics, exposure
      assessments based on interviews within 1 week among the exposed physiotherapists
      were compared with exposure assessments based on observations including
      measurements. It was possible to discriminate between recent high and low peak
      exposure. Furthermore, an interview index reflecting the duration of the exposure
      correlated to some extent with the corresponding measurements.

PMID- 1989438
TI  - Improved method for the adjustment of urinary delta-aminolevulinic acid
      concentration.
AB  - The work was aimed at finding whether the ratio of delta-aminolevulinic acid
      (ALA) and creatinine (Cn) concentration (ALA/Cn), presently used in occupational
      health practice for evaluation of lead exposure gives a better assessment of ALA
      excretion than uncorrected ALA concentration itself, as well as at finding a
      better, but not complicated method for adjustment. ALA and Cn concentrations were
      measured in untimed urine samples of altogether 390 men and women (age: 18-60
      years) not occupationally exposed to lead. In agreement with others, ALA/Cn was
      found to be an unsuitable method of adjustment for the differences in ALA
      concentration due to the different concentrations of samples. This can be
      explained by the different renal handling of ALA and Cn, proved by the literature
      data. The exponential relationship between ALA/Cn and Cn concentration raised the
      possibility of adjustment to the logarithm of Cn concentration (ALA/log.Cn). This
      simple method provided a more reliable index, the value of which was independent
      of the actual Cn concentration of urines within a wide range (2-32 mmol/liter).
      The recommended biological limit value (70 mumol/log.Cn mmol) separates equally
      well from normal values, both in dilute and concentrated urines. The evaluation
      of occupational lead exposure might be more reliable using this index, instead of
      uncorrected ALA concentration or the ALA/Cn ratio.

PMID- 1989439
TI  - Are non-whites at greater risk for occupational cancer?
AB  - All occupational cancer epidemiology articles that reported data on non-whites
      from four major journals were identified for the years 1984-1987. In addition to
      these 14 papers, four more papers were identified from computer searches, and
      another 13 were found by following up references from the original 14. Within
      these 31 papers, there were 36 analyzable cohorts (subgroups by job and sex).
      Five cohorts had elevated all-cancer mortality ratios in non-whites without an
      increase in whites. Sixteen cohorts showed elevated ratios in both racial groups,
      with 11 of the 16 having a higher non-white cancer mortality ratio than white
      cancer mortality ratio. For the 25 studies in which at least one racial group's
      cancer ratio was elevated, the non-white ratio exceeded the white ratio in 17
      (68%). The overall paucity of articles on non-white cancer mortality, as well as
      the apparent trend toward increased occupational cancer mortality in non-whites,
      is discussed.

PMID- 1989441
TI  - Preventing is better than fixing.

PMID- 1989440
TI  - Retrospective cohort mortality study of cancer among sewage plant workers.
AB  - There is little known about the incidence of cancer among sewage workers. In this
      paper we examine findings from a retrospective cohort study of 487 white male
      sewer authority workers employed between January 1950 and October 1979. Vital
      status was ascertained for 93% of the cohort yielding a total of 6,886 person
      years. Total mortality from all causes was comparable to that of the general
      white male U.S. population (Standardized Mortality Ratio [SMR] = 0.91, 95%
      Confidence Interval [CI] = 0.77-1.07). The cohort was subdivided into those not
      exposed, and sewer workers who were exposed to sewage effluent, sludge, or
      wastewater containing chemicals including potential carcinogens. Among the
      nonexposed group, mortality from all causes was significantly low (SMR = 0.55,
      95% CI = 0.33-0.88). Among the exposed sewer workers, mortality from all causes
      was not significantly different from that of the general white male U.S.
      population (SMR = 1.00, 95% CI = 0.84-1.19). Mortality from all cancers among
      exposed sewer workers was slightly higher than that of the general population
      (SMR = 1.19, 95% CI = 0.79-1.7). Statistically significant elevated mortality
      ratios were seen for cancer of the larynx (SMR = 7.93, 95% CI = 1.59-23.96), and
      cancer of the liver (SMR = 5.4, 95% CI = 1.10-16.05). Careful study of the
      medical and occupational histories of these cases suggested that larynx cancer
      was possibly work-related, while liver cancer was not. A group estimated to be
      the highest exposed, composed predominantly of operatives, had a higher directly
      adjusted death rate from all malignant neoplasms combined compared to all other
      workers (rate ratio = 1.64). These findings of increased risk of cancer among
      exposed sewage workers, especially operators, are based on small number of cases
      and should be interpreted with caution. Studies of larger cohorts are needed to
      clarify the risk of these cancers among sewage workers.

PMID- 1989442
TI  - Habit management.

PMID- 1989443
TI  - More on men in nursing.

PMID- 1989444
TI  - Security interest.

PMID- 1989445
TI  - Solid gains behind, leaner times ahead.

PMID- 1989446
TI  - How to take a precise blood pressure.

PMID- 1989447
TI  - Fear of caring: the feminist paradox.

PMID- 1989448
TI  - Is it really Alzheimer's?

PMID- 1989449
TI  - How to assess your unit before you take report.

PMID- 1989450
TI  - Healing with hydrocolloid.

PMID- 1989451
TI  - I.V. inquiry.

PMID- 1989452
TI  - Transrectal ultrasound: a new screening tool for prostate cancer.

PMID- 1989453
TI  - Let's identify the Yellowhearts in our midst.

PMID- 1989454
TI  - Pacific states jobfocus. New frontiers in ambulatory care.

PMID- 1989456
TI  - Specialty jobfocus. Opportunities in rehabilitation nursing.

PMID- 1989455
TI  - Southern California jobfocus. Southern California: carefree and caring.

PMID- 1989457
TI  - Cutaneous lymphadenoma.
AB  - Thirteen cases of a unique cutaneous tumor are presented. The lesions presented
      as single, nondescript, skin-color nodules. Eleven were located on the head and
      two were on the legs. The male/female ratio was 8:5. The age at diagnosis ranged
      between 21 and 55 years (mean: 39). The duration of the lesions was from several
      months to more than 20 years. All tumors were excised and did not recur. The
      tumors typically presented as well-circumscribed nodules with scant or no
      epidermal connections. (One example, however, had a plate-like configuration
      amply connected with the basal layers of the epidermis.) The proliferation
      consisted of multiple, rounded lobules of basaloid cells with some degree of
      peripheral palisading, immersed in a dense, fibrous stroma. There was an intense
      infiltrate of small lymphocytes within the lobules, with some spillage into the
      stroma. No clear adnexal differentiation was noted except for rare isolated cells
      showing apparent sebaceous differentiation within the tumor lobules. Areas of
      central keratinization were also present. Numerous cells with ample amphophilic
      cytoplasm, large vesicular nuclei, and prominent nucleoli were also seen.
      Immunohistochemistry confirmed the presence of keratin within tumor cells. Common
      leukocytic antigen highlighted the intense intralobular lymphocytic component.
      Vimentin not only highlighted the stromal fibroblastic component, but also
      stained scattered intralobular cells. Epithelial membrane antigen was positive
      within some of the large intraepithelial cells. S-100 protein was extensively
      positive within dendritic intralobular and stromal cells. Lymphocytic markers
      demonstrated a polyclonal B and T population. This unique tumor appears to
      represent a form of adnexal neoplasm with basaloid features, possibly immature
      pilosebaceous differentiation.

PMID- 1989458
TI  - Effect of combination endocrine therapy (LHRH agonist and flutamide) on normal
      prostate and prostatic adenocarcinoma. A histopathologic and immunohistochemical
      study.
AB  - The histopathology of 23 radical prostatectomies from patients with prostatic
      adenocarcinoma pretreated for 3-6 months with combination therapy including a
      luteinizing hormone-releasing hormone agonist and the antiandrogen drug flutamide
      was reviewed and compared with the pretreatment biopsies or transurethral
      resection material. After combination therapy, benign prostatic glands showed
      marked atrophy with prominent basal-cell layers, basal-cell hyperplasia, and
      epithelial-cell vacuolization. Immature squamous-cell metaplasia was present in
      seven cases. Residual carcinoma, on the other hand, was found in 19 of the 23
      cases, and in 8 of these, tumor cells were either vacuolated or had scanty
      cytoplasm. Residual tumor was present as only one focus in 13 cases, and in 3 of
      these it was composed of single cells with a "hemangiopericytoma-like" pattern.
      An immunohistochemical study for prostatic acid phosphatase and prostatic
      specific antigen could be carried out on paraffin blocks from 19 biopsies and 18
      prostatectomies. After combination therapy, a reduction in staining (intensity
      and number of positive cells) was observed for the two markers in both normal
      prostate and carcinoma but with more pronounced effects on the latter. The
      present data show that temporary combination therapy before radical prostatectomy
      causes marked and very characteristic changes in normal prostatic tissue as well
      as in the prostatic tumor. These histologic patterns enter the differential
      diagnosis of a variety of atrophic, metaplastic, and proliferative lesions of the
      prostate gland. The pathologist must be aware of these histologic changes when
      looking at biopsy or resection material of treated patients.

PMID- 1989459
TI  - Solitary fibrous tumor of the nasal cavity and paranasal sinuses.
AB  - We report two solitary fibrous tumors of the nasal cavity and paranasal sinuses
      that were histologically and immunohistochemically virtually identical to
      solitary fibrous tumors (fibrous mesotheliomas) of the pleura. One tumor arose in
      a 48-year-old woman and the other in a 45-year-old woman. Both patients presented
      with nasal symptoms, and both patients are alive without evidence of disease 6
      months and 1 year after excision. The tumors had a disorganized or "patternless"
      arrangement of spindle cells in a collagenous background and prominent vascular
      channels of varying size. Immunoperoxidase stains on paraffin sections showed
      staining of the cells for vimentin only; there was no staining for keratin, S-100
      protein, desmin, and actin. Both cases presented some degree of diagnostic
      difficulty and had to be distinguished from other spindle cell tumors of the
      nasal cavity and paranasal sinuses, such as hemangiopericytoma, angiofibroma, and
      fibrous histiocytoma.

PMID- 1989460
TI  - Giant multilocular prostatic cystadenoma: a distinctive lesion of the
      retroperitoneum in men. A report of two cases.
AB  - Two examples of large, multiloculated, cystic tumors that arose within the pelvis
      in men of 28 and 37 years of age are described. The tumors were composed of
      glands and cysts lined by prostatic-type epithelium lying in a hypocellular
      fibrous stroma. The prostatic nature of the lesions was confirmed by
      immunohistochemical staining of the epithelium for prostate-specific antigen and
      prostatic acid phosphatase. Two apparently similar lesions were found in the
      literature; one tumor was attached to the prostate by a pedicle, and the other
      arose in the retrovesical space. These tumors, for which we propose the
      designation "giant multilocular prostatic cystadenoma," appear to be benign,
      although they may recur if incompletely excised. They may pose considerable
      diagnostic difficulty if the prostatic nature of the epithelium is not
      appreciated, an error that is likely if a relationship to the prostate is not
      recognized. This lesion should be included in the differential diagnosis of
      retroperitoneal cystic tumors in men.

PMID- 1989461
TI  - Role of the transitional mucosa of the colon in differentiating primary
      adenocarcinoma from carcinomas metastatic to the colon. An immunohistochemical
      study.
AB  - Differentiation between primary colonic adenocarcinoma arising in flat mucosa and
      carcinoma metastatic to the colon is often difficult. Examination of the mucosa
      adjacent to the tumor, the so-called transitional mucosa (TM), may be helpful.
      The morphologic, ultrastructural, and histochemical characteristics of the TM
      have been reported previously in detail. In this study the morphologic and
      immunohistochemical characteristics of the TM have been compared in 18 cases of
      primary colonic adenocarcinoma and 13 cases of metastasis to the colon. Five
      immunophenotypic markers were used: carcinoembryonic antigen (CEA), Lewis (x) and
      (y) blood group antigens, ras oncogene p21, and tumor-associated glycoprotein
      (TAG-72). Neoplastic transformation of colonic epithelium is associated with
      altered expression of these antigens. The morphologic and immunohistochemical
      profile of the TM was similar in both primary colonic adenocarcinomas and
      metastases to the colon. In some cases the TM adjacent to colonic metastases
      stained with one or more antibodies while the metastatic tumor was negative.
      Therefore, in cases where differentiation between primary colonic adenocarcinoma
      arising in flat mucosa and metastasis is difficult, the use of these reagents,
      particularly CEA, TAG-72, or ras oncogene p21, may be helpful. The similar
      immunohistochemical staining pattern of the TM in both primary and metastatic
      colon lesions supports a reactive, non-neoplastic origin of the TM. Furthermore,
      expression of these antigens is not limited to neoplastic epithelial cells.

PMID- 1989462
TI  - Immunocytochemical analysis of estrogen and progesterone receptors in benign
      stromal lesions of the breast. Evidence for hormonal etiology in
      pseudoangiomatous hyperplasia of mammary stroma.
AB  - Five cases of pseudoangiomatous hyperplasia of mammary stroma, together with
      seven examples of mammary hamartoma, were probed with monoclonal antibodies H222
      and KD68 to investigate the possible role of estrogen and progesterone receptor
      expression in the pathogenesis of these benign stromal proliferations. All five
      cases of pseudoangiomatous hyperplasia showed patchy, intense labelling of the
      stromal cells with progesterone receptor antibodies, a pattern contrasting
      markedly with the absence of immunoreactivity in normal (nongestational) mammary
      stroma or the stromal component of common juvenile mammary hyperplasia. The
      stroma of the hamartoma group labeled inconsistently, with the notable exception
      of three myoid hamartomas. Stromal immunoreactivity was diffuse and intense in
      two of these, and patchy and distinct in the remaining case. These findings (a)
      support the contention that pseudoangiomatous hyperplasia represents a localized
      form of stromal overgrowth with a hormonal (primarily progestagenic) etiology and
      (b) further highlight the heterogeneity of so-called mammary hamartomas by
      demonstrating dramatically different progesterone receptor immunoreactivity
      patterns in myoid lesions as compared with other hamartoma variants.

PMID- 1989464
TI  - Anaplastic thyroid carcinoma with osteoclast-like giant cells. A
      clinicopathologic, immunohistochemical, and ultrastructural study.
AB  - Two anaplastic thyroid carcinomas with osteoclast-like giant cells (OCL-GC) are
      reported. Light microscopically, one case resembled an aneurysmal bone cyst with
      cellular connective-tissue septae separating cavernous, blood-filled sinuses. The
      second case had sheets of anaplastic cells and a separate focus of papillary
      carcinoma without areas of transition. Multinucleate OCL-GC, pleomorphic
      mononuclear cells, and histiocytoid mononuclear cells with nuclei similar to
      those within the OCL-GC were seen in each case. With formalin-fixed, paraffin
      embedded tissue, the majority of OCL-GC and histiocytoid mononuclear cells in
      both cases showed immunoreactivity using monoclonal antibodies to vimentin and KP
      1, with the latter preparation directed against cells of monocytic/histiocytic
      lineage. Staining for keratin, epithelial membrane antigen, neuron-specific
      enolase, chromogranin, calcitonin, and thyroglobulin was negative in all cell
      types. Ultrastructural examination of one case showed two distinct types of
      mononuclear cells--one with morphologic characteristics similar to those of the
      OCL-GC, and another with pleomorphic nuclei and short cytoplasmic extensions
      joined by poorly formed desmosomes. The findings indicate that the anaplastic
      thyroid carcinomas studied represent poorly differentiated epithelial tumors
      infiltrated by reactive OCL-GC of monocytic/histiocytic lineage apparently
      derived from histiocytoid mononuclear cells via cellular fusion.

PMID- 1989463
TI  - Deep juvenile xanthogranuloma. Subcutaneous and intramuscular forms.
AB  - Juvenile xanthogranuloma occurring in soft tissue is rare and has received little
      attention. This report describes cases of deep juvenile xanthogranuloma occurring
      in the soft tissues of three children. Each tumor was a solitary lesion that
      arose, respectively, in the superficial skeletal muscles of an 8-month-old girl,
      the subcutis of the scalp of a 3-month-old boy, and the subcutis of the forehead
      of a 10-year-old girl. Two lesions were grossly firm, tan-yellow, and
      homogeneous. Histologically, the subcutaneous lesions were relatively
      circumscribed; the third lesion infiltrated muscle and contained widely separated
      skeletal muscle fibers. All lesions showed sheets of uniform amphophilic or
      acidophilic cells with occasional eosinophils and rare Touton giant cells. In two
      cases and in cutaneous controls, positive immunoperoxidase stains (HAM-56, HHF
      35, and vimentin) supported macrophagic-myofibroblastic differentiation. S-100
      protein, MAC-387, and factor XIIIa were negative. Electron microscopy in one case
      also supported macrophagic-myofibroblastic differentiation. Langerhans granules
      were absent. Follow-up of 7, 6, and 5 years indicated no recurrences. The
      differential diagnosis includes deep fibrous histiocytoma and cellular
      subcutaneous neural tumors.

PMID- 1989465
TI  - Extraction of DNA from paraffin blocks for Southern blot analysis.
AB  - Tissues stored as paraffin blocks are a potential source of DNA for retrospective
      clinicogenetic analysis. To assess the feasibility of Southern blot analysis, DNA
      extracted from paraffin blocks was compared with DNA obtained from fresh-frozen
      controls of the same tissues. Sections 50-100 microns thick cut from paraffin
      blocks of 11 normal tissues, 18 lymphoid lesions, and 9 gastric carcinoma samples
      were deparaffinized and incubated at 45 degrees C for 48 to 72 h in a sodium
      dodecyl sulfate (SDS)/proteinase K solution. Following organic extraction,
      alcohol precipitation, restriction endonuclease digestion, and gel
      electrophoresis, DNA was transferred to nylon membranes. 32P-labelled DNA probes
      for the immunoglobulin heavy-chain locus and T-cell receptor beta-chain gene were
      hybridized to the normal tissue and lymphoid samples; the gastric cancers were
      probed for the HER-2/neu protooncogene. Intact DNA was obtained from the majority
      of formalin-fixed samples, yielding results qualitatively similar to those from
      fresh tissues. Degradation is the most significant problem in analyzing DNA
      extracted from paraffin blocks and compromises accurate quantitation. DNA
      analysis using paraffin-embedded tissue has potential clinical and research
      applications and may be a particularly useful way to study gene abnormalities in
      unusual tumors infrequently available as fresh specimens.

PMID- 1989466
TI  - Congenital, infiltrating giant-cell angioblastoma. A new entity?
AB  - This report describes histopathologic, immunohistologic, and ultrastructural
      features of a locally aggressive soft-tissue tumor present since birth in an
      upper extremity of an infant. Because of extensive infiltration of local
      structures, the lesion had to be treated by amputation. The outstanding
      histologic feature consisted of nodular cell clusters resembling inflammatory
      granulomas, often with giant, multinucleated cells. On the basis of our findings,
      these cellular aggregates were interpreted as distorted attempts at formation of
      vessels. This interpretation was strengthened by the more obviously vascular
      structure of the tumor in many areas. A high content of stromal cells positive
      for factor XIIIa and histocompatability antigen (HLA)-DR was a characteristic
      that the tumor shared in common with angiomatoid malignant fibrous histiocytoma.
      However, there were also important differences that singularize the tumor
      described in the present study. We could find no closely comparable precedent for
      a lesion with these characteristics in current treatises on infantile soft-tissue
      tumors.

PMID- 1989467
TI  - Occult stomach symptoms?

PMID- 1989469
TI  - ANA spurs evolution of programs for homeless.

PMID- 1989468
TI  - Medicare pay reform may change pay for advanced practice nurses.

PMID- 1989470
TI  - OR nursing--fulfilling! Challenging!

PMID- 1989471
TI  - Nurse authors share writing tips.

PMID- 1989472
TI  - Nation ready to learn from nurses.

PMID- 1989473
TI  - Time to value social caring. Interview by Patricia McCarty.

PMID- 1989475
TI  - Health care reform is ANA priority for 102nd Congress.

PMID- 1989474
TI  - Getting published. Guidelines for prospective authors.

PMID- 1989476
TI  - Write for publication? Who, me?

PMID- 1989477
TI  - Communication is risk management tool for RNs.

PMID- 1989478
TI  - Mobilizing nurses for health care reform.

PMID- 1989479
TI  - Larger RN role seen in health care reform. As I see it.

PMID- 1989480
TI  - Liability crisis hurts patients, taxpayers. As I see it.

PMID- 1989481
TI  - Governmental affairs--the process and the power.

PMID- 1989482
TI  - Agency looks to nurses to improve health care.

PMID- 1989484
TI  - Nursing home staffing regulations still ambiguous.

PMID- 1989483
TI  - Laws empower nurses as independent providers.

PMID- 1989486
TI  - New drug regulations may impact on nursing care.

PMID- 1989485
TI  - ANA seeks law barring strike replacements.

PMID- 1989487
TI  - Women's health deserves more attention.

PMID- 1989488
TI  - Influence of the surface potential on the purple membrane structure and activity.
AB  - The role of the divalent cations in the purple membrane is generally understood
      as the release mechanism of the blue form appearance. The reconstitution by
      cation addition leads to the recovery of the initial spectral properties.
      Numerous data are available in the literature on this matter but they are
      scattered, so that synthetic understanding is not easy. The role of divalent
      cations was studied through spectrophotometric titrations and electrophoretic
      mobility measurements, i.e., zeta potential valuations. Thus, correlations
      between the bacteriorhodopsin (bR) state and the whole membrane in equilibrium
      with a definite medium could be made. Deionization was not a fully reversible
      process. The absence of cations affect neither the rate of the M412 formation nor
      its lifetime but the yield of M412/bR was 50% lower. The number of protons
      involved in the blue to purple transition of both membranes was different and the
      reconstitution did not erase this difference. It was observed that the number of
      protons dissociated upon cation addition corresponded approximately to the number
      of positive charges removed by deionization. Electrophoretic mobility titrations
      showed large differences between the membranes, illustrating the influence of the
      surface charge density on the pK of the transition. Taking advantage of the
      reversible light adaptation process, the reciprocal influence of the charge
      density of the membrane surface and the retinal state in bR was shown.
      Specificity of the divalent cations was questioned by a direct substitution of
      them by imidazol, which left the membrane intact. The partial reversibility of
      the deionization, the decrease of the M412 yield, the differences in the
      titratable protons, and the nonstrict specificity toward divalent cations
      suggested that another unknown factor could be removed from the membrane.

PMID- 1989489
TI  - Intrinsic fluorescence of the bacterial copper-containing protein amicyanin.
AB  - The fluorescence properties of the single tryptophanyl residue present in
      amicyanin from Thiobacillus versutus are very similar to those of azurin from
      Pseudomonas aeruginosa and other mononuclear blue copper proteins. The emission
      maximum is well structured and centered at 318 nm. The quantum yield is strongly
      affected by the presence of copper, the removal of which is accompanied by a more
      than sixfold increase in fluorescence, without change in shape. The fluorescence
      decay of holo-amicyanin is heterogeneous with a longer component of 5.7 ns and a
      shorter one of 0.7 ns accounting for 90% of the total emitting molecules. Copper
      free amicyanin shows instead a single exponential decay (3.3 ns) of intrinsic
      fluorescence. This lifetime decreases as the temperature increases as does the
      longer lifetime component of holoamicyanin.

PMID- 1989490
TI  - Purification and characterization of histidinol dehydrogenase from cabbage.
AB  - Histidinol dehydrogenase (EC 1.1.1.23) activity was determined in several plant
      species and in cultured plant cell lines. The enzyme was purified from cabbage
      (Brassica oleracea) to apparent homogeneity. To render complete purification, a
      new, specific histidinol-Sepharose 4B affinity chromatography was developed. The
      apparent molecular mass of the protein is 103 kDa. On sodium dodecyl sulfate
      polyacrylamide gel electrophoresis, the protein migrated as a single band with a
      molecular mass of 52 kDa, giving evidence for a dimeric quaternary structure. By
      isoelectric focusing, the enzyme was separated into six protein bands, five of
      which possessed the dehydrogenase activity when examined by an activity staining
      method. The Km values for L-histidinol and NAD+ were 15.5 and 42 microM,
      respectively. Enzyme activity was stimulated by addition of Mn2+, but was
      inhibited in the presence of Ba2+, Mg2+, Ni2+, Ca2+, Zn2+, or Cu2+. Histidinol
      dehydrogenase is the first histidine enzyme that has been purified to homogeneity
      and characterized from plants. This plant enzyme catalyzes the NAD-linked four
      electron dehydrogenase reaction leading from histidinol to His. The results
      indicate a similar pathway of His in plants and show furthermore the last two
      reaction steps to be identical to those in microorganisms.

PMID- 1989491
TI  - Tertiary and quaternary structural differences between two genetic variants of
      bovine casein by small-angle X-ray scattering.
AB  - The casein complexes of bovine milk consist of four major protein fractions,
      alpha s1, alpha s2, beta, and kappa. Colloidal particles of casein (termed
      micelles) contain inorganic calcium and phosphate; they are very roughly
      spherical with an average radius of 650 A. Removal of Ca2+ leads to the formation
      of smaller protein aggregates (submicelles) with an average radius of 94 A. Two
      genetic variants, A and B, of the predominant fraction, alpha s1-casein, result
      in milks with markedly different physical properties, such as solubility and heat
      stability. To investigate the molecular basis for these differences, small-angle
      X-ray scattering was performed on the respective colloidal micelles and
      submicelles. Scattering curves for submicelles of both variants showed multiple
      Gaussian character; data for the B variant were previously interpreted in terms
      of two concentric regions of different electron density, i.e., a "compact" core
      and a relatively "loose" shell. For the submicelle of A, there was a third
      Gaussian, reflecting a negative contribution due to interparticle interference.
      Molecular parameters for submicelles of both A and B are in agreement with
      hydrodynamic data in the literature. Data for the micelles, for which scattering
      yields cross-sectional information, were fitted by a sum of three Gaussians for
      both variants; for these, the corresponding two lower radii of gyration represent
      the two concentric regions of the submicelles, while the third reflects the
      average packing of submicelles within the micellar cross section. Most of the
      molecular parameters obtained showed small but consistent differences between A
      and B, but for submicelles within the micelle several differences were
      particularly notable: A has a greater molecular weight for the "compact" region
      of the constituent submicelle (82,000 vs 60,000) and a much greater submicellar
      packing number (6:1 vs 3:1). Reasons for these and other differences are to be
      sought in sequence differences and in differences in calcium-binding sites and
      charge distribution.

PMID- 1989492
TI  - Purification and characterization of p-coumaroyl-D-glucose hydroxylase of sweet
      potato (Ipomoea batatas) roots.
AB  - p-Coumaroyl-D-glucose hydroxylase in sweet potato (Ipomoea batatas Lam.) has been
      purified to apparent electrophoretic homogeneity using a combination of anion-and
      cation-exchange, hydrophobic and gel filtration chromatography. The purified
      enzyme was a monomer with a molecular weight of 33,000 and pI of 8.3. The
      purified enzyme showed not only hydroxylase activity but also polyphenol oxidase
      activity. L-Ascorbic acid was the best electron donor for the hydroxylation
      reaction, which had an optimum pH of 7.0. The enzyme hydroxylated p-coumaroyl-D
      glucose, p-coumaric acid, and p-cresol but did not act on o-coumaric acid, m
      coumaric acid, 4-hydroxy-3-methoxycinnamic acid, p-hydroxybenzoic acid or L
      tyrosine. While the enzyme utilized p-coumaroyl-D-glucose and p-coumaric acid
      equally at pH 7.0, it hydroxylated only p-coumaroyl-D-glucose at pH 5.5. The
      enzyme oxidized diphenols such as D,L-(3,4-dihydroxyphenyl) alanine and caffeic
      acid, but exhibited no clear pH optimum in this reaction characteristic of
      polyphenol oxidase. Both the hydroxylase and the polyphenol oxidase activities
      were strongly inhibited by beta-mercaptoethanol, diethyldithiocarbamate, KCN, and
      p-coumaric acid (in concentrations higher than 5 mM). Ammonium sulfate and sodium
      chloride activated the hydroxylase activity but not the polyphenol oxidase
      activity of the enzyme. The enzyme activity and L-ascorbic acid contents changed
      in a manner suggesting their involvements in chlorogenic acid biosynthesis during
      incubation of sliced sweet potato root tissues.

PMID- 1989494
TI  - Effect of single amino acid substitutions at positions 49 and 60 on the thermal
      unfolding of the tryptophan synthase alpha subunit from Salmonella typhimurium.
AB  - We have used circular dichroism measurements to compare the thermal unfolding of
      the wild type tryptophan synthase alpha subunit from Salmonella typhimurium with
      that of seven mutant forms with single amino acid replacements at two active site
      residues. Glutamic acid 49 has been replaced by phenylalanine, glutamine, or
      aspartic acid. Aspartic acid 60 has been replaced by alanine, aspartic acid,
      asparagine, or tyrosine. Thermodynamic properties (delta G, delta H, delta S, and
      Tm) of the wild type and mutant forms have been determined experimentally by
      measuring the free energy of unfolding as a function of temperature. Increasing
      the pH from 7.0 to 8.8 decreases the tm of the wild type alpha subunit from 56 to
      45 degrees C. The thermal unfolding of the wild type alpha subunit and of six of
      the seven mutant forms can be described as reversible, two-state transitions. In
      contrast, the melting curve of a mutant alpha subunit in which aspartic acid 60
      is replaced by tyrosine indicates the presence of a folding intermediate which
      may correspond to a "molten globule." Correlations between our observations and
      previous folding studies and the X-ray crystallographic structure are presented.
      Substitution of glutamic acid 49, which is located in the hydrophobic "pit" of an
      eight-fold alpha/beta barrel, by a hydrophobic phenylalanine residue increases
      the tm from 56 to 60 degrees C. In contrast, replacement of aspartic acid 60,
      which is accessible to solvent, results in small reductions in the thermal
      stability.

PMID- 1989493
TI  - Stereoisomerism in plant disease resistance: induction and isolation of the 7,2'
      dihydroxy-4',5'-methylenedioxyisoflavone oxidoreductase, an enzyme introducing
      chirality during synthesis of isoflavonoid phytoalexins in pea (Pisum sativum L).
AB  - Treatment of pea seedlings with CuCl2 induced the activity of the enzyme
      NADPH:7,2'-dihydroxy-4',5'-methylenedioxyisoflavone oxidoreductase (DMIRase) that
      introduces (+) stereoisomerism in pisatin. DMIRase was purified approximately
      7000 fold from CuCl2-treated pea seedlings to apparent homogeneity by a six-step
      process. The purification sequence included (NH4)2SO4 fractionation, gel
      filtration on AcA 44, chromatography on DEAE-Bio-Gel,phenyl-Sepharose CL-4B, and
      Reactive Red 120-agarose, and sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. Gel filtration and denaturing electrophoresis showed that the
      enzyme consisted of a single polypeptide chain with an Mr of 37,500. The pH
      optimum of DMIRase was determined to be 7.8. The enzyme showed apparent Michaelis
      constants of 20 microM for 7,2'-dihydroxy-4',5'-methylenedioxyisoflavone and 58
      microM for NADPH. The reaction product of the enzyme, sophorol, gave a distinct
      negative Cotton effect in the region 300-360 nm, which indicated 3S configuration
      of the molecule. Antibodies against the enzyme were raised in rabbits and
      characterized for specificity.

PMID- 1989495
TI  - Zeta-crystallin from guinea pig lens is capable of functioning catalytically as
      an oxidoreductase.
AB  - zeta-Crystallin, a major taxon-specific protein of the guinea pig lens, has been
      shown to be distantly related to the alcohol/polyol dehydrogenase family and to
      specifically bind NADPH. The capacity of zeta-crystallin to function
      catalytically was investigated in the present study. zeta-Crystallin exhibited an
      NADPH-dependent oxidoreductase activity with 2,6-dichlorophenolindophenol (DCIP).
      The NADPH:DCIP oxidoreductase activity of zeta-crystallin exhibits a linear
      response with increasing protein concentration, and saturation kinetics with
      NADPH and DCIP. This activity was abolished by heat inactivation and
      immunoadsorption of the protein. Dicumarol, Cibacron blue, manganese, and
      sulfhydryl reagents were inhibitory.

PMID- 1989496
TI  - A ribosomal protein S6 kinase copurifies with phosphatase-1 activating factor.
AB  - A highly purified preparation of phosphatase-activating kinase (Fa) from rabbit
      skeletal muscle phosphorylated ribosomal protein S6. The two activities
      copurified on DEAE-Sephadex, CM-Sephadex, and phosphocellulose chromatography and
      upon further chromatography on Sephacryl S-300 and FPLC Mono-S and Mono-Q
      columns. On the latter column, two separate peaks of Fa activity were observed
      when it was developed in Tris buffer as opposed to beta-glycerophosphate. S6
      kinase activity was obtained only with the Fa which adhered to the resin. The Mr
      of the Fa and S6 activities was determined to be 83,200 by gel permeation on a
      Sephacryl S-300 column. The Fa preparation phosphorylated serine residues on S6;
      two tryptic phosphopeptides, A and C, were identified by two-dimensional
      phosphopeptide analysis. The enzyme also showed good activity toward initiation
      factor eIF-4B. Based on specificity toward ribosomal proteins and initiation
      factors, the Fa and a mitogen-stimulated S6 kinase purified from insulin
      stimulated 3T3-L1 cells were similar. These results suggest that a form of Fa and
      an insulin-stimulated S6 kinase may be related or closely associated.

PMID- 1989497
TI  - Developmental changes in the expression of S-acyl fatty acid synthase
      thioesterase gene and lipid composition in the uropygial gland of mallard ducks
      (Anas platyrhynchos).
AB  - Developmental changes in the composition of the uropygial gland secretory lipids
      of the postembryonic mallard ducks (Anas platyrhynchos) were determined. During
      the first 3 weeks after hatching, the composition of the secretory lipids
      remained constant; the lipids consisted of long-chain wax esters composed of a
      complex mixture of n-, monomethyl, and dimethyl fatty acids esterified to n-C16
      and n-C18 fatty alcohols. Afterward, as the ducks began to acquire adult
      feathers, short-chain wax esters composed of 2- and 4-monomethyl fatty acids
      began to appear with 2-methylhexanoyl and 4-methylhexanoyl as the major acyl
      components; esters of short-chain monomethyl fatty acids (less than or equal to
      C12) constituted 90% of the lipids when the ducks were 2 months old and had
      acquired adult plumage. The appearance of the short-chain acids in the acyl
      portion of the wax esters was accompanied by the appearance of S-acyl fatty acid
      synthase thioesterase, which can hydrolytically release short-chain acids from
      fatty acid synthase in the gland. Northern blot analysis showed that the gland
      specific thioesterase gene transcripts began to appear in the gland only 3 weeks
      after hatching. The appearance of the transcripts and immunologically detectable
      thioesterase protein reached maximum levels 2 months after hatching, with the
      acquisition of the adult plumage. Thus, the developmental changes in lipid
      composition correlated with the changes in the level of expression of the
      thioesterase gene. Expression of other gland-specific genes has been previously
      found to begin just prior to hatching. The gland-specific thioesterase is the
      first case of delayed expression of a gland-specific gene.

PMID- 1989498
TI  - The enzymatic activity of human cytotoxic T-lymphocyte granzyme A and cytolysis
      mediated by cytotoxic T-lymphocytes are potently inhibited by a synthetic
      antiprotease, FUT-175.
AB  - The synthetic antiprotease, FUT-175 (6-amidino-2-naphthyl-4-guanidinobenzoate),
      was found to be an extraordinarily potent and rapid inhibitor of human Q31
      cytotoxic T-lymphocyte granzyme A. The granzyme A was inhibited in a time
      dependent manner with kobs/i = 430,000 +/- 80,000 M-1 s-1. Four other FUT-175
      analogs were also found to be potent, rapid Q31 granzyme A inhibitors. All five
      compounds inhibited Q31 cytotoxic T-lymphocyte-mediated cytolysis of human JY
      lymphoma cells, but at concentrations far in excess of those needed for granzyme
      A inhibition. The data presented suggest that postmarketing surveillance of FUT
      175 should include a review of possible immunosuppressive side-effects, such as
      increased susceptibility to viral infections and to neoplastic transformations.

PMID- 1989499
TI  - Inhibition of mammalian thymidylate synthase by 10
      formyltetrahydropteroylpolyglutamate.
AB  - Reduced derivatives of 10-formylfolate have been evaluated as inhibitors of
      mammalian thymidylate synthase (EC 2.1.1.45) from H35 hepatoma cells. With 5,10
      methylenetetrahydrofolylheptaglutamate as the substrate, 10
      formyltetrahydrofolylmonoglutamate is a competitive inhibitor with a Ki of 2.4
      microM, which is reduced to 0.1 microM for the heptaglutamate derivative. 10
      Formyldihydrofolylmono- and -heptaglutamate are approximately threefold less
      inhibitory than the tetrahydro analog. The concentrations of 10
      formyltetrahydrofolate and 10-formyldihydrofolate were measured in dividing
      hepatoma cells by a novel enzymatic assay and were found to be 5 microM and
      undetectable, respectively. These results suggest that the concentration of 10
      formyltetrahydrofolate within the dividing cells has the potential to severely
      inhibit or modulate thymidylate biosynthesis.

PMID- 1989500
TI  - Tissue-specific induction of the carcinogen inducible cytochrome P450 isoform,
      P450IAI, in colonic epithelium.
AB  - The epithelial cells of the gastrointestinal tract have the capacity to engage in
      biotransformation of ingested chemicals. A principal component of phase I
      metabolism of xenobiotics is the family of hemeproteins referred to as
      cytochrome(s) P450. The presence of cytochrome P450 isoforms was examined by
      Western blot analysis in the epithelial cells of the colon and proximal small
      intestine of male rats following oral administration with either beta
      naphthoflavone or phenobarbital. The appearance of beta-naphthoflavone-inducible
      cytochrome P450IAI was observed in the colon and small intestine. The appearance
      of this cytochrome P450 isoform was concurrent with increases (up to 150-fold) in
      cytochrome P450-related O-deethylation of 7-ethoxycoumarin and 7-ethoxyresorufin
      in both tissues. Following administration of phenobarbital, cytochrome P450IIBI
      was identified immunochemically in the small intestine. However, this isozyme
      could not be detected in colon. These data suggest that the epithelial cells of
      the proximal small intestine respond to beta-naphthoflavone and phenobarbital in
      a manner similar to the liver, whereas colonic epithelial cells may have a
      greater capacity to respond to P450IAI-type inducers such as beta-naphthoflavone.
      Evidence exists that differences in cytochrome P450 isozyme composition can
      affect the ultimate metabolic fate of ingested chemicals, including carcinogens,
      and thus a role for colonic P450-dependent monooxygenase activity in the
      biogenesis of cancer in this tumor-susceptible tissue is suggested.

PMID- 1989501
TI  - A simple method for calculating the dissociation constant of a receptor (or
      enzyme).unlabeled ligand complex from radioligand displacement measurements.
AB  - A general procedure is described for determining the dissociation constant of a
      receptor (or enzyme).unlabeled ligand complex (EI) by analyzing the I-dependent
      displacement of bound radioligand (A*) from EA*. The procedure (which involves
      measuring free A* in the presence of I) requires a knowledge of the total
      concentrations of receptor ([E]t), unlabeled ligand ([I]t) and radioligand
      ([A*]t), and the dissociation constant of the EA* complex. The unknown Kd is
      obtained from five simple, sequential calculations which are valid for either
      high or low affinity competitive unlabeled ligands and are independent of total
      receptor concentration or initial degree of saturation with A*. The procedure
      also provides the information needed to construct a distribution curve of all
      enzyme and ligand species (E, EA*, EI, A*, I) as [I]t is varied.

PMID- 1989502
TI  - Stimulation of phospholipase A2 activity in human platelets by trypsin and
      collagen.
AB  - Type I collagen enhanced human platelet phospholipase A2 activity whether added
      to platelet-rich plasma or washed platelets. The stimulatory effect of type I
      collagen on platelet membrane phospholipase A2 activity was also observed in a
      cell-free system utilizing platelet membranes. The release of arachidonic acid
      was enhanced by types I and III but not by type V collagen. The activation of
      platelet phospholipase A2 by type I collagen was inhibited by soybean trypsin
      inhibitor and mimicked by trypsin. However, type I collagen addition was not
      associated with any detectable changes in platelet membrane proteins while
      trypsin altered many proteins. These results point to acid soluble phospholipase
      A2 activity of platelets as an enzyme activated by type I collagen.

PMID- 1989503
TI  - Molecular mechanism of spider silk elasticity.
AB  - Spider major ampullate (drag-line) silk is an extracellular fibrous protein which
      has impressive characteristics of strength and elasticity. This silk has been
      hypothesized to predominantly consist of a single protein, containing regions of
      antiparallel beta-sheets which are interspersed with amorphous segments
      responsible for its elastic properties. A rubber-like mechanism has been
      suggested to account for this elasticity, but the specific molecular mechanism is
      unknown. Using Fourier transform infrared spectroscopy (FTIR) we found evidence
      of either helix formation or reorientation of preexisting helices when axial
      tension is applied to the spider silk fiber. CD studies of a peptide derived from
      the silk gene repeat sequence show that it can form beta-sheets at high
      temperatures while alpha-helices are induced in 2,2,2-trifluoroethanol. These
      results suggest a possible molecular mechanism for the elasticity of spider silk
      fibers. It is proposed that the elastic process involves the formation and
      disruption of alpha-helical Ala-rich regions which are interspersed among stable
      beta-sheet domains.

PMID- 1989504
TI  - Casein kinase I phosphorylates the 25-kDa mRNA cap-binding protein.
AB  - The 25-kDa mRNA cap-binding protein (eIF-4E) exists in both phosphorylated and
      dephosphorylated forms in eukaryotic cells. Phosphorylated eIF-4E appears to be
      preferentially associated with 48 S initiation complexes and with the 220-kDa
      subunit of eIF-4F. In addition, dephosphorylation of eIF-4E has been observed
      during heat shock and mitosis which are accompanied by decreased protein
      synthesis. However, the control of eIF-4E phosphorylation and its regulatory role
      remain poorly understood. Using eIF-4E as a substrate we have identified and
      purified from rabbit reticulocytes a protein kinase that phosphorylates eIF-4E in
      vitro. This enzyme phosphorylated eIF-4E on both serine and threonine residues
      with an apparent Km of 3.7 microM. The molecular mass of the enzyme and
      specificity for substrates other than eIF-4E suggested that this enzyme was a
      species of casein kinase I. This was confirmed by comparing the phosphopeptide
      map of the purified reticulocyte enzyme with that of rabbit skeletal muscle
      casein kinase I and by comparing phosphopeptide maps of eIF-4E phosphorylated in
      vitro by each enzyme. We conclude that casein kinase I phosphorylates eIF-4E in
      vitro and suggest that eIF-4E may be phosphorylated by casein kinase I in intact
      cells under some physiologic conditions.

PMID- 1989505
TI  - Mutagenesis of the folC gene encoding folylpolyglutamate synthetase-dihydrofolate
      synthetase in Escherichia coli.
AB  - The folC gene of Escherichia coli, cloned in a pUC19 vector, was mutagenized by
      progressive deletions from both the 5' and the 3' ends and by TAB linker
      insertion. A number of 5'-deleted genes, which had the initiator ATG codon
      removed, produced a truncated gene product, in reduced amounts, from a secondary
      initiation site. The most likely position of this site at a GTG codon located 35
      codons downstream of the normal start site. This product could complement the
      folC mutation in E. coli strain SF4 as well as a strain deleted in the folC gene.
      The specific activity of extracts of the mutant enzyme are 4-16% that of the wild
      type enzyme for the folylpolyglutamate synthetase activity and 6-19% for the
      dihydrofolate synthetase activity. The relative amount of protein expressed by
      the mutant, compared to the wild type, in maxicells was comparable to the
      relative specific activity, suggesting that the kcat of the mutant enzyme is
      similar to that of the wild type. Mutants with up to 14 amino acids deleted from
      the carboxy terminal could still complement the folC deletion mutant. Seven out
      of ten linker insertions dispersed through the coding region of the gene showed
      complementation of the folC mutation in strain SF4 but none of these insertion
      mutants were able to complement the strain containing a deleted folC gene. None
      of the carboxy terminal or linker insertion mutants had a specific activity
      greater than 0.5% that of the wild type enzyme. The dihydrofolate synthetase and
      folylpolyglutamate synthetase activities behaved similarly in all mutants, both
      retaining a large fraction of the wild type activity in the amino terminal
      deletions and both being very low in the carboxy terminal deletions and linker
      insertion mutants. These studies are consistent with a single catalytic site for
      the two activities catalyzed by this enzyme.

PMID- 1989506
TI  - Studies on dilution inactivation of sheep liver pyruvate carboxylase.
AB  - When sheep liver pyruvate carboxylase was diluted below 4 EU/ml, it underwent
      inactivation involving two kinetically distinct processes, i.e., a rapid initial
      burst followed by a slower second phase. The catalytic activity of the diluted
      enzyme eventually approached zero, suggesting the occurrence of an irreversible
      process. Analysis of the quaternary structure of the enzyme by gel filtration
      chromatography and electron microscopy showed that most of the enzyme molecules
      occur as tetramers at high enzyme concentrations. However, dilution of the enzyme
      below 4 EU/ml led to the appearance of dimers and monomers which were essentially
      inactive under the conditions of the assay system used. The presence of acetyl
      CoA during dilution prevented inactivation from occurring and preserved the
      tetrameric structure. When added after dilution, acetyl-CoA prevented further
      inactivation from occurring but did not reactivate the enzyme. However, acetyl
      CoA did cause a relatively rapid reassociation of the inactive monomers and
      dimers to form inactive tetramers.

PMID- 1989507
TI  - Change in activity of nuclear poly(ADP-ribose) glycohydrolase during the HeLa S3
      cell cycle.
AB  - The change in activity of nuclear poly(ADP-ribose) glycohydrolase during the cell
      cycle of HeLa S3 cells was investigated. The poly(ADP-ribose) glycohydrolase
      activity was solubilized from HeLa S3 cell nuclei and chromosomes only by
      sonication at high ionic strength. The enzyme hydrolyzed poly(ADP-ribose)
      exoglycosidically, producing ADP-ribose. After release from mitosis, the activity
      of the solubilized nuclear poly(ADP-ribose) glycohydrolase per nucleus or per
      unit protein, assayed with [3H]poly(ADP-ribose) (average chain length, n = 15) as
      substrate, was lowest in the early G1 phase and highest in the late G1 phase. The
      specific activity in the late G1 phase was about two times that in the early G1
      phase. The high activity remained constant during the S-G2-M phase. A similar
      change during the cell cycle was observed after release from hydroxyurea block.
      These results suggest that the activity of poly(ADP-ribose) glycohydrolase
      doubled during the G1 phase of the cell cycle of HeLa S3 cells.

PMID- 1989508
TI  - Developmental changes in actin and myosin heavy chain isoform expression in
      smooth muscle.
AB  - Smooth muscle cells express isoforms of actin and myosin heavy chains (MHC). In
      early postnatal animals the nonmuscle (NM) actin and MHC isoforms in vascular
      (aorta) smooth muscle were present in relatively high percentages. More than 30%
      of the MHC and 40% of the actin isoforms were NM. The relative percentage of the
      NM isoforms decreased significantly as the animals reached maturity, with NM MHC
      less than 10% and NM actin less than 30% of the totals. Concurrent with this
      decrease in NM isoforms was an increase in the smooth muscle (SM) isoforms. The
      relative changes and time frame in which these changes occurred were very similar
      for the actin and MHC isoforms. In arterial tissue there were species differences
      for changes with development in the two SM MHC isoforms (SM1 and SM2). The ratio
      of SM1:SM2 in young rat aorta was approximately 0.5, while this same ratio was
      approximately 3 in young swine carotid. Both adult rats and swine had a SM1:SM2
      MHC ratio of approximately 1.2. Rat bladder smooth muscle showed no significant
      change in NM vs SM ratio between young and old rats, while the SM1:SM2 ratio
      decreased from 2.7 to 1.7 between these age groups. The shifts in alpha and beta
      actin were similar to those in the vascular tissue, but of much smaller
      magnitude.

PMID- 1989509
TI  - Characterization of human spermidine/spermine N1-acetyltransferase purified from
      cultured melanoma cells.
AB  - Extreme inducibility of spermidine/spermine acetyltransferase (SSAT) by bis-ethyl
      derivatives of spermine in human large cell lung carcinoma and melanoma cells has
      prompted biochemical characterization of the purified enzyme. Treatment of human
      MALME-3 melanoma cells with 10 microM N1,N11-bis(ethyl)norspermine (BENSPM) for
      48-72 h increased SSAT activity by some 1000- to 4000-fold and enabled
      purification of the enzyme by established procedures--binding on immobilized
      spermine and elution with spermine followed by binding on Matrex Blue A and
      elution with coenzyme A. The enzyme showed a single band by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis with a single subunit species and
      molecular weight of approximately 20,300 Da. By gel permeation chromatography,
      the holoenzyme was found to have a molecular weight of 80,000 Da, suggesting a
      total of four identical subunits. Purified SSAT had a specific activity of 285
      mumol/min/mg for spermidine and Km values of 5.9 microM for acetylcoenzyme A, 55
      microM for spermidine, 5 microM for spermine, 36 microM for N1-acetylspermine,
      1.6 microM for norspermidine, and 4 microM for norspermine. Homologs of BENSPM
      were found to be competitive inhibitors of spermidine acetylation, with Ki values
      of 0.8 microM for BENSPM, 1.9 microM for N1,N12-bis-(ethyl)spermine and 17 microM
      for N1,N14-bis-(ethyl)-homospermine. Correlation of these values with the
      relative abilities of the homologs to increase SSAT in intact cells suggests that
      formation of an enzyme inhibitor complex may play a contributing role in enzyme
      induction.

PMID- 1989511
TI  - Purification and characterization of Contractin A from the pedicellarial venom of
      sea urchin, Toxopneustes pileolus.
AB  - A component that causes contraction of the isolated guinea pig tracheal smooth
      muscle was isolated in homogeneous form from the venom of the pedicellaria of the
      sea urchin, Toxopneustes pileolus. It is named Contractin A. Contractin A has
      18,000 Da with a total residue of 138 amino acids. The molecular weight is about
      17,700. The N-terminal amino acid is serine. The partial amino acid sequence was
      determined up to 37 residues. Direct comparison of sea urchin Contractin A does
      not show any similarity in amino acid sequence to toxins isolated from other
      marine toxin producers such as sea snakes, sea anemones, or marine worms.
      Contractin A caused contraction of the tracheal smooth muscle in a dose-dependent
      manner. Furthermore, Contractin A relaxed the contraction induced by histamine.
      The contraction and relaxation activity of Contractin A on the tracheal smooth
      muscle is reduced by a cyclooxygenase inhibitor such as indomethacin. The
      contraction induced by Contractin A is also inhibited by a phospholipase C
      inhibitor but not by a phospholipase A2 inhibitor. These results suggest that in
      the isolated guinea pig tracheal smooth muscle, the response to Contractin A may
      be effected through activated phospholipase C.

PMID- 1989510
TI  - Stereochemical studies of the C-methylation of deoxycytidine catalyzed by HhaI
      methylase and the N-methylation of deoxyadenosine catalyzed by EcoRI methylase.
AB  - The steric course of methyl group transfer catalyzed by two DNA methylases, HhaI
      methylase, a DNA (cytosine-5)-methyltransferase, and EcoRI methylase, which
      methylates at N6 of adenosine, has been studied with (methyl-R)- and (methyl-S)
      [methyl-2H1,3H]adenosylmethionine as the methyl donor, using as substrates poly
      d(GC) (HhaI) and the dodecamer oligonucleotide duplex d(CGCGAATTCGCG) (EcoRI),
      respectively. The methylated nucleotides were degraded to convert the chiral
      methyl groups into acetic acid for configurational analysis. It was found that
      both enzymatic reactions proceed with inversion of configuration of the methyl
      group.

PMID- 1989513
TI  - A specific acyl-ACP thioesterase implicated in medium-chain fatty acid production
      in immature cotyledons of Umbellularia californica.
AB  - Umbellularia californica (California Bay) seeds accumulate 10:0 and 12:0 as
      principal reserve fatty acyl groups. An in vitro fatty acid synthesis system from
      the developing cotyledons produces chiefly 10:0 and 12:0, in approximately the
      same proportions as the intact tissue. The kinetics of acyl thioester and free
      fatty acid formation in this system suggest that a medium-chain specific acyl
      acyl-carrier protein (ACP) hydrolysis mechanism is responsible for the
      preponderance of medium-chain products. A crude extract of the developing
      cotyledons exhibits hydrolytic activity toward acyl-ACPs, with marked preference
      for 12:0-ACP and 18:1-ACP in the test series 6:0, 8:0, 10:0, 11:0, 12:0, 14:0,
      16:0, and 18:1-ACPs. Partial purification of the 12:0-ACP hydrolytic activity has
      resulted in its separation from the 18:1-ACP hydrolase(s) and the 12:0-coenzyme A
      hydrolase(s) that are also present, thereby demonstrating its specificity for the
      12-carbon acyl chain length and the ACP derivative. During cotyledon development,
      as the proportion of medium-chain to other fatty acyl groups increases, the
      extractable yield of this activity also increases substantially. Collectively
      these results suggest a role for this 12-ACP thioesterase in medium-chain
      production in vivo.

PMID- 1989512
TI  - Kinetic mechanism of the endogenous lactate dehydrogenase activity of duck
      epsilon-crystallin.
AB  - Initial velocity, product inhibition, and substrate inhibition studies suggest
      that the endogenous lactate dehydrogenase activity of duck epsilon-crystallin
      follows an order Bi-Bi sequential mechanism. In the forward reaction (pyruvate
      reduction), substrate inhibition by pyruvate was uncompetitive with inhibition
      constant of 6.7 +/- 1.7 mM. In the reverse reaction (lactate oxidation),
      substrate inhibition by L-lactate was uncompetitive with inhibition constant of
      158 +/- 25 mM. The cause of these inhibitions may be due to epsilon-crystallin
      NAD(+)-pyruvate and epsilon-crystallin-NADH-L-lactate abortive ternary complex
      formation as suggested by the multiple inhibition studies. Pyruvate binds to free
      enzyme very poorly, with a very large dissociation constant. Bromopyruvate,
      fluoropyruvate, pyruvate methyl ester, and pyruvate ethyl ester are alternative
      substrates for pyruvate. 3-Acetylpyridine adenine dinucleotide, nicotinamide 1,N6
      ethenoadenine dinucleotide, and nicotinamide hypoxanthine dinucleotide serve as
      alternative coenzymes for epsilon-crystallin. All the above alternative
      substrates or coenzymes showed an intersecting initial-velocity pattern
      conforming to the order Bi--Bi kinetic mechanism. Nicotinic acid adenine
      dinucleotide, thionicotinamide adenine dinucleotide, and 3-aminopyridine adenine
      dinucleotide acted as inhibitors for this enzymatic crystallin. The inhibitors
      were competitive versus NAD+ and noncompetitive versus L-lactate. alpha-NAD+ was
      a noncompetitive inhibitor with respect to the usual beta-NAD+. D-Lactate,
      tartronate, and oxamate were strong dead-end inhibitors for the lactate
      dehydrogenase activity of epsilon-crystallin. Both D-lactate and tartronate were
      competitive inhibitors versus L-lactate while oxamate was a competitive inhibitor
      versus pyruvate. We conclude that the structural requirements for the substrate
      and coenzyme of epsilon-crystallin are similar to those of other dehydrogenases
      and that the carboxamide carbonyl group of the nicotinamide moiety is important
      for the coenzyme activity.

PMID- 1989514
TI  - Oxidation of chlorpromazine by methemoglobin in the presence of hydrogen
      peroxide. Formation of chlorpromazine radical cation and its covalent binding to
      methemoglobin.
AB  - The oxidation of chlorpromazine by methemoglobin plus H2O2 has been studied. The
      transient formation of the chlorpromazine radical cation in this reaction has
      been demonstrated by light absorption measurements. Under the experimental
      conditions complete conversion of chlorpromazine yields approximately 60%
      chlorpromazine sulfoxide. From studies with 3H-labeled chlorpromazine it appears
      that the remaining 40% is covalently bound to apohemoglobin. Upon reaction of
      methemoglobin with H2O2 a stable ferrylhemoglobin is formed. This
      ferrylhemoglobin is not the reactive species, which accepts the chlorpromazine
      electron, as its presence is not sufficient to induce chlorpromazine oxidation.
      For this the presence of H2O2 is a prerequisite. This indicates that a transient
      species in the formation of the stable ferrylhemoglobin is involved, whether this
      is a compound I analogue or a ferrylhemoglobin with a free radical on one of the
      apoprotein residues. Exposition of methemoglobin to H2O2 denatures hemoglobin and
      induces protein-heme crosslinks, as appears from changes in the visible
      absorption spectrum and heme retention by the protein after methyl ethyl ketone
      extraction. Reaction with CPZ partly protects against denaturation and
      crosslinking.

PMID- 1989516
TI  - Role of peroxisomal fatty acyl-CoA beta-oxidation in phospholipid biosynthesis.
AB  - We have already reported that peroxisomal beta-oxidation has an anabolic
      function, supplying acetyl-CoA for bile acid biosynthesis [H. Hayashi and A.
      Miwa, 1989, Arch. Biochem. Biophys. 274, 582-589]. The anabolic significance of
      peroxisomal beta-oxidation was further investigated in the present study by using
      clofibrate, a peroxisome proliferator, as an experimental tool. Clofibrate
      suppressed 3-hydroxymethylglutaryl-CoA reductase activity (the key enzyme of
      cholesterol synthesis) and enhanced fatty acyl-CoA oxidase activity (the rate
      limiting enzyme of beta-oxidation). Rats were fed a chow containing 0.25%
      clofibrate for 2 weeks, and then a bile duct fistula was implanted. [1
      14C]lignoceric acid, which is degraded exclusively by peroxisomal FAOS, was
      injected into the rats 24 h after the operation. By this time, the secondary bile
      acids and pooled cholesterol which would normally be secreted into the bile are
      considered to have been exhausted from the liver. Clofibrate significantly
      decreased the incorporations of radioactivity into biliary bile acid (40% of the
      control) and cholesterol (50%), but did not affect biliary lipid contents.
      [14C]Acetyl-CoA formed by peroxisomal beta-oxidation of [1-14C]lignoceric acid
      was preferentially utilized for syntheses of long-chain fatty acids and
      phospholipids rather than synthesis of cholesterol or triglyceride. The
      radioactivities incorporated into the former two lipids were increased 2-fold
      over the control by administration of clofibrate, while the incorporation into
      triglyceride was decreased to approximately half. In particular, the
      incorporation into phosphatidylethanolamine was increased as much as 3.5-fold
      over the control. The contents of these lipids in the liver were not affected by
      clofibrate. The results suggest that peroxisomal beta-oxidation plays an
      important role in the biosynthesis of functional lipids such as phospholipids
      (this work), in addition to bile acids and cholesterol (previous report) by
      supplying acetyl-CoA.

PMID- 1989515
TI  - Purification and partial characterization of intestinal-like alkaline phosphatase
      in rabbit kidney.
AB  - Two types of alkaline phosphatase (AP) isozymes in rabbit kidney, a major
      intestinal-like type and a minor tissue-unspecific type, have been identified.
      The former enzyme was purified from rabbit kidney by immunoaffinity
      chromatography using monoclonal anti-human intestinal AP antibody. The purified
      enzyme yielded a single protein band on sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis, and the apparent molecular size of its monomer subunit was found
      to be 72,000. Three amino acid residues within the first 16 N-terminal amino acid
      residues were different in purified AP and human intestinal AP. Although the
      rabbit enzyme possessed some peptide bands identical to those of human adult
      intestinal AP after Staphylococcus aureus V8 protease digestion, the enzyme did
      not react with monoclonal antibody against human adult intestinal AP alone,
      whereas it did react with monoclonal antibody against both human adult and fetal
      intestinal APs. The affinity of the enzyme for concanavalin A was identical to
      that of the fetal intestinal AP, but different from that of the adult enzyme.
      These results indicate that the antigenicity and certain properties of purified
      rabbit AP are more like those of human fetal intestinal AP or Kasahara isozyme,
      so-called intestinal-like AP, than like human adult intestinal AP.

PMID- 1989518
TI  - Purification, physicochemical characterization, and immunohistochemical
      localization of a major 11.7 S glycoprotein from the jelly coats of the anuran
      Lepidobatrachus laevis.
AB  - Embryos of the frog Lepidobatrachus laevis are encased by a fertilization
      envelope and two jelly layers, termed J1 (innermost) and J2 (outermost). From
      preparations of total jelly solubilized from cleavage-stage embryos by a solution
      of alkaline beta-mercaptoethanol we have purified one jelly coat glycoprotein to
      homogeneity via FPLC gel permeation chromatography on Superose 6H. The purified
      glycoprotein was 94% protein and 6% carbohydrate, had an s0(20),w of 11.7 S, with
      a molecular weight of 245,000 measured by sedimentation equilibrium and 263,000
      by gel permeation chromatography. SDS-PAGE revealed that the glycoprotein is
      composed of a single subunit near 29,700 molecular weight; thus we propose that
      eight of these subunits comprise the native molecule. Amino acid analysis of the
      glycoprotein indicated a high content of Glx + Asx (32.4 mole%), a low content of
      basic amino acids (Arg + Lys = 12.2 mole%), and a single cysteine residue per
      subunit. The N-terminal amino acid was threonine and the sequence of the first
      twenty amino acids was determined. Monospecific antisera to the glycoprotein were
      prepared in rabbits and were used to immunohistochemically localize the
      glycoprotein throughout the matrix of both jelly layers. Antiserum against the
      glycoprotein had virtually no effect on the fertilizability of jellied eggs in
      vitro; thus we hypothesize that the glycoprotein fulfills a structural role in
      both jelly layers.

PMID- 1989517
TI  - Effect of aging on the activity of the phosphate carrier and on the lipid
      composition in rat liver mitochondria.
AB  - The effect of aging on the activity of the phosphate carrier and on the lipid
      composition in rat liver mitochondria has been investigated. It was found that
      the rate of phosphate transport in mitochondria from aged rats (28 months old) is
      significantly reduced (around 40%) compared to that obtained in mitochondria from
      young control rats (5 months old). Kinetic analysis of the phosphate transport
      indicates that only the Vmax of this process is affected, while there is no
      change in the Km values. The lower activity of the phosphate carrier in
      mitochondria from aged rats is also documented by swelling experiments. The age
      related decrement in the activity of the phosphate carrier was found not to be
      due neither to a change in the endogenous content of phosphate nor to a change in
      the transmembrane delta pH value. Inhibitor titrations with mersalyl provide no
      evidence for a lower content of functional phosphate translocase in mitochondria
      from aged rats. There is no difference either in the respiratory control ratios
      or in the ADP/O ratios between mitochondria from young and aged animals. The
      hepatic mitochondrial lipid composition is altered significantly in aged rats:
      the total cholesterol increases (31%), the phospholipids decrease (12%), and the
      cholesterol/phospholipid molar ratio increases (44%). Among the phospholipids
      cardiolipin shows the greatest alteration (30% decrease with age). Alterations
      were also found in the pattern of fatty acids. The age-related decrement in the
      activity of the phosphate carrier appears to be dependent on changes in the lipid
      domain surrounding the carrier protein molecule in the mitochondrial membrane.

PMID- 1989519
TI  - Ethanol increases cytochromes P450IIE, IIB1/2, and IIIA in cultured rat
      hepatocytes.
AB  - In intact rats, ethanol treatment has been associated with increases in hepatic
      levels of both P450IIB1/2 and P450IIE. When rat hepatocytes were cultured on an
      extracellular tumor matrix (Matrigel), exposure to ethanol from 48 to 96 h in
      culture resulted in increases in cytochromes P450IIE, IIB1/2, and IIIA.
      Cytochrome P450IIE was detected immunologically and enzymatically, using two
      activities associated with cytochrome P450IIE, p-nitrophenol hydroxylation, and
      acetaminophen activation to a metabolite that binds to glutathione. The content
      of cytochrome P450IIE in freshly isolated cells decreased when the cells were
      placed in culture. Exposure of the cultured hepatocytes to ethanol from 48 to 96
      h after inoculation resulted in an increase in cytochrome P450IIE compared to
      untreated cultured cells. In addition, in culture, the amount of enzymatically
      active protein after ethanol treatment was equal to that in hepatocytes freshly
      isolated from intact animals. Ethanol treatment resulted in increases in
      cytochrome P450IIB1/2 compared to untreated cells, as shown immunologically and
      by increased benzyloxyresorufin dealkylase activity. However, phenobarbital
      induced cytochrome P450IIB1/2 to higher levels, compared to ethanol. Ethanol and
      phenobarbital treatments both increased P450IIIA, as determined immunologically
      and by the amount of propoxycoumarin depropylase activity that is inhibited by
      triacetyloleandomycin. However, the amount of P450IIIA increased after ethanol
      treatment was less than that increased after treatment with dexamethasone in
      these cells. The ethanol-mediated increases in all four forms of cytochrome P450
      in culture suggest that these increases in the intact animal result from direct
      effects of ethanol on the liver.

PMID- 1989520
TI  - Temperature dependence of the dissociation rate constants for 8 S, 4 S, and
      meroreceptor forms of the estrogen receptor from rat uterus.
AB  - Conversion of a steroid receptor complex from the 8 S to the 4S form results in
      new interactions between the steroid and the receptor and/or formation of new
      intra-protein bonds within the receptor molecule itself. These bonds must be
      broken before the steroid is released. In order to localize these newly formed
      interactions, the dissociation kinetics of meroreceptors derived from 4 S and 8 S
      (molybdate-stabilized) receptor complexes were examined. At temperatures between
      6 and 30 degrees C, no differences in the rates of dissociation were observed for
      the meroreceptors derived from the two forms of estrogen receptor, whereas
      approximately a twofold difference in dissociation rates for 4 S intact receptor
      versus 8 S intact receptor was detected. These findings indicate that the new
      interactions accompanying this conversion are likely to occur in regions of the
      receptor molecule other than the C-terminal portion of the steroid-binding site.
      The thermodynamic parameters of the dissociation reaction for the intact 4 S, and
      8 S, and meroreceptor forms, respectively were: delta H [symbol; see text] = 26.2
      +/- 1.3, 19.7 +/- 1.7, and 23.2 +/- 1.0 kcal/mol; +T delta S [symbol; see text] =
      9.4 +/- 1.2, 3.2 +/- 1.7 and 6.6 +/- 0.9 kcal/mol (at 25 degrees C); and delta G
      [symbol; see text] = 16.8 +/- 2.5, 16.5 +/- 3.4, and 16.7 +/- 1.9 kcal/mol. As is
      the case for other steroid receptors, an increase in the enthalpy of steroid
      receptor interaction after this conversion reflects the stability of the 4 S
      estrogen receptor complex.

PMID- 1989521
TI  - Fluorescence characteristics of peroxidation products in porcine intestinal brush
      border membranes.
AB  - Treatment of the porcine intestinal brush-border membranes with 100 microM
      ascorbic acid and 10 microM Fe2+ in the presence of various concentrations of
      tert-butyl hydroperoxide (t-BuOOH) resulted in a marked fluorescence development
      at 430 nm, depending on the hydroperoxide concentration. This fluorescence
      formation was closely related to lipid peroxidation of the membranes as assessed
      by formation of conjugated diene. However there is no linear relation between
      thiobarbituric acid-reactive substances (TBARS) and fluorescence formation. On
      the other hand, fluorescence formation in the membranes by treatment with
      ascorbic acid/Fe2+ or t-BuOOH alone was negligible. The results with antioxidants
      and radical scavengers suggest that ascorbic acid/Fe2+/t-BuOOH-induced lipid
      peroxidation of the membranes is mainly due to t-butoxyl and/or t-butyl peroxy
      radicals. Most TBARS produced during the peroxidation reaction were released from
      the membranes, but fluorescent products remained in the membrane components. The
      fluorescence properties of products formed by lipid peroxidation of the membranes
      were compared with those of products derived from the interaction of
      malondialdehyde (MDA) or acetaldehyde with the membranes. The fluorescence
      products in the acetaldehyde-modified membranes also exhibited the emission
      maximum at 430 nm, while the emission maximum of MDA-modified membranes was 470
      nm. The fluorescence intensity of MDA-modified membranes was markedly decreased
      by treatment with 10 mM NaBH4 but that of the peroxidized or acetaldehyde
      modified membranes was enhanced by about two-fold with the treatment. In
      addition, a pH dependence profile revealed that the fluorescence intensity of the
      peroxidized or acetaldehyde-modified membranes decreases with increasing pH of
      the medium, whereas that of MDA-modified ones did not change over the pH range
      from 5.4 to 8.0. On the basis of these results, the fluorescence properties of
      products formed in the intestinal brush-border membranes by lipid peroxidation
      are discussed.

PMID- 1989522
TI  - Ribozymes that cleave an RNA sequence from human immunodeficiency virus: the
      effect of flanking sequence on rate.
AB  - Ribozymes designed to cleave sequences specific to viral RNA may be better
      antiviral agents than simple antisense oligonucleotides. High catalytic activity
      with the lowest possible chain length is desired for this purpose. We have
      synthesized several hammerhead ribozymes that cleave sequences from HIV-1 RNA. On
      reducing from 20 to 12 the base pairs formed with the substrate, the rate of
      cleavage at 37 degrees C increased 10-fold. Deletions from the stem/loop
      structure in the ribozyme also increased the initial rate of reaction.

PMID- 1989523
TI  - Comparison of proteoglycans synthesized by porcine normal and polycystic renal
      tubular epithelial cells in vitro.
AB  - Newly synthesized porcine tubular epithelial cell proteoglycans were labeled in
      vitro with Na2[35S]SO4. At the beginning of the labeling period (24 h) [35S]
      sulfate incorporated into macromolecules was measured following PD-10
      chromatography. There was a significant reduction in the amount of 35S-labeled
      macromolecules isolated from polycystic cells compared to that from normal cells.
      The distribution of recovered radiolabeled material among the medium, cell
      surface, and intracellular fractions was similar for both normal and polycystic
      cells. Analysis of the proteoglycans in polycystic cells demonstrated that 86 and
      73% of 35S-labeled macromolecules were of the heparan sulfate type in polycystic
      and normal cells, respectively. The remainder was chondroitin sulfate.
      Proteoglycans were characterized using DEAE-Sephacel ion-exchange chromatography,
      chondroitinase ABC, heparitinase, and nitrous acid digestion followed by
      Sepharose CL-4B gel permeation chromatography. The majority of radiolabeled
      material in the medium, cell surface, and intracellular fractions eluted between
      0.35 and 0.39 M NaCl. However, a second peak (peak II) that eluted at 0.25 M NaCl
      was found in the medium from polycystic cells. This peak accounted for 27% of the
      total macromolecules secreted into the medium. Proteoglycans in the major peak
      were susceptible to nitrous acid and chondroitinase ABC digestion. A similar
      proportion of peak II was degraded by chondroitinase ABC. However, the remainder
      was only slightly susceptible to treatment with nitrous acid or heparitase. In
      normal cells a small amount of material eluted at a similar low charge; the
      proteoglycans were the same as those found in the major peak and appeared as a
      shoulder on this peak.

PMID- 1989524
TI  - Role of cytochrome P450 IA2 in acetanilide 4-hydroxylation as determined with
      cDNA expression and monoclonal antibodies.
AB  - The role of P450 IA2 in the hydroxylation of acetanilide was examined using an
      inhibitory monoclonal antibody (MAb) 1-7-1 and vaccinia cDNA expression producing
      murine P450 IA1 (mIA1), murine P450 IA2 (mIA2), or human P450 IA2 (hIA2).
      Acetanilide hydroxylase (AcOH) activity was measured using an HPLC method with
      more than 500-fold greater sensitivity than previously described procedures. This
      method, which does not require the use of radioactive acetanilide, was achieved
      by optimizing both the gradient system and the amount of enzyme needed to achieve
      detection by uv light. MAb 1-7-1 inhibits up to 80% of the AcOH activity in both
      rat liver microsomes and cDNA expressed mouse and human P450 IA2. MAb 1-7-1,
      which recognizes both P450 IA1 and P450 IA2, completely inhibits the aryl
      hydrocarbon hydroxylase (AHH) activity of cDNA expressed in IA1. The inhibition
      of only 80% of the AHH activity present in MC liver microsomes by MAb 1-7-1
      suggests that additional P450 forms are contributing to the overall AHH activity
      present in methylcholanthrene (MC)-liver microsomes as MAb 1-7-1 almost
      completely inhibits the AHH activity of expressed mIA1. Maximal inhibition of IA2
      by 1-7-1 results in an 80% decrease in acetanilide hydroxylase activity in both
      liver microsomes and expressed mouse and human IA2. The capacity of MAb 1-7-1 to
      produce identical levels of inhibition of acetanilide hydroxylase activity in rat
      MC microsomes (80%) and in expressed mouse (81%) and human P450 IA2 (80%)
      strongly suggests that P450 IA2 is the major and perhaps the only enzyme
      responsible for the metabolism of acetanilide. These results demonstrate the
      complementary utility of monoclonal antibodies and cDNA expression for defining
      the contribution of specific P450 enzymes to the metabolism of a given substrate.
      This complementary approach allows for a more precise determination of the
      inhibitory capacity of MAb with respect to the metabolic capacity of the target
      P450.

PMID- 1989525
TI  - Isolation and characterization of the major glycosphingolipids from the liver of
      the rainbow trout (Oncorhynchus mykiss): identification of an abundant source of
      9-O-acetyl GD3.
AB  - The carbohydrate structures of the major glycosphingolipids from the liver of the
      rainbow trout Oncorhynchus mykiss have been examined. We have isolated and
      identified four major neutral (glucosylceramide, galactosylceramide,
      lactosylceramide, and globoside) and five acidic (sulfatide, GM3, GM2, GD1a, and
      9-O-Acetyl GD3) glycosphingolipids from trout liver. They have been characterized
      by 1H nuclear magnetic resonance spectroscopy, methylation analysis, fast atom
      bombardment mass spectrometry, and specific monoclonal antibodies. Significantly,
      the relatively scarce ganglioside 9-O-acetyl GD3 was found to comprise
      approximately 23% of the total ganglioside content of normal rainbow trout liver.
      9-O-Acetyl GD3 is, however, abundant in human melanoma and as such, trout liver
      may be a suitable source of this antigen.

PMID- 1989526
TI  - Inhibition of iodoacetamide and t-butylhydroperoxide toxicity in LLC-PK1 cells by
      antioxidants: a role for lipid peroxidation in alkylation induced cytotoxicity.
AB  - Previously we reported that thiol depletion and lipid peroxidation were
      associated with the cytotoxicity of nephrotoxic cysteine S-conjugates, a group of
      toxins which kill LLC-PK1 cells after metabolic activation and covalent binding.
      To determine if this is a general mechanism of cytotoxicity in these cells, we
      compared the effect of antioxidants, an iron chelator, and a thiol reducing agent
      on the toxicity of an alkylating agent, iodoacetamide (IDAM), and an organic
      peroxidant, t-butylhydroperoxide (TBHP). IDAM or TBHP toxicity was concentration
      (0.01 to 1.0 mM) and time (1 to 6 h) dependent. Both toxins caused lipid
      peroxidation which occurred prior to cell death as determined by leakage of
      lactate dehydrogenase (LDH). The alkylating agent IDAM bound to cellular
      macromolecules and depleted cellular non-protein thiols almost completely by 1 h,
      while LDH release occurred first at 2 to 3 h. The toxicity of IDAM and TBHP was
      inhibited by the antioxidants DPPD, BHA, BHQ, PGA, and BHT and the iron chelator
      deferoxamine. However, DPPD blocked TBHP- and IDAM-induced lipid peroxidation and
      toxicity without affecting binding and depletion of cellular nonprotein thiols.
      Furthermore, the thiol reducing agent dithiothreitol was able to block lipid
      peroxidation and toxicity. Therefore it is possible that with an alkylating
      agent, depletion of cellular nonprotein thiols cooperates with covalent binding
      and contributes to lipid peroxidation and cell death. There appear to be common
      elements in the toxicity of alkylating agents and organic peroxidants in LLC-PK1
      cells.

PMID- 1989527
TI  - The role of cytochrome b5 in delta 12 desaturation of oleic acid by microsomes of
      safflower (Carthamus tinctorius L.).
AB  - The electron donors for the membrane-bound fatty acid desaturases of higher
      plants have not previously been identified. In order to assess the participation
      of cytochrome b5 in microsomal fatty acid desaturation, the cytoplasmic domain of
      microsomal cytochrome b5 was purified from Brassica oleracea, and murine
      polyclonal antibodies were prepared. The IgG fraction from ascites fluid
      inhibited 62% of NADH-dependent cytochrome c reduction in safflower (Carthamus
      tinctorius L.) microsomes. These antibodies also blocked desaturation of oleic
      acid to linoleic acid in lipids of C. tinctorius microsomes by 93%, suggesting
      that cytochrome b5 is the electron donor for the delta 12 desaturase.

PMID- 1989528
TI  - Pulmonary embolectomy.

PMID- 1989529
TI  - Retrograde continuous warm blood cardioplegia.

PMID- 1989530
TI  - Emergency aortocoronary bypass after failed angioplasty.
AB  - One thousand two hundred fourteen percutaneous transluminal coronary
      angioplasties were performed over a 38-month period. Sixty patients required
      immediate emergency coronary artery bypass grafting after angioplasty failure; 7
      of these had evidence of acute myocardial infarction before angioplasty and were
      excluded from the study. Of the 53 patients remaining, 27 (51%) had
      electrocardiographic and enzyme evidence of postoperative myocardial infarction.
      Two patients died (4%), and 10 had postoperative complications (19%). No
      statistical significance was noted comparing age, sex, incidence of prior
      myocardial infarction or myocardial dysfunction, time for revascularization, or
      average number of grafts completed in those with single-vessel (n = 21) versus
      multiple-vessel (n = 32) coronary artery disease. Postoperatively, those with
      multiple-vessel disease required intraaortic balloon pump support (p = 0.06) and
      antiarrhythmic medications more frequently than single-vessel patients (p less
      than 0.01) and had a higher complication rate (p less than 0.05). Although not
      reaching statistical significance, the data also suggest a higher death and
      postoperative myocardial infarction rate in patients with multiple-vessel
      disease. Emergency coronary artery bypass grafting after failed percutaneous
      transluminal coronary angioplasty carries a higher morbidity and mortality than
      elective coronary artery bypass grafting, particularly for patients with multiple
      vessel coronary artery disease.

PMID- 1989531
TI  - Long-term results of Ionescu-Shiley valve in the tricuspid position.
AB  - A retrospective analysis of the long-term results of using the Ionescu-Shiley
      pericardial bioprosthesis in the tricuspid position was carried out on 73
      patients (8 men, 65 women). Of these procedures, ten were tricuspid valve
      replacement alone and the remainder were in combination with other valve
      procedures. The mean follow-up was 9.6 years (range, 4 to 18 years). The mean age
      of the patients was 53 years (range, 27 to 78 years). Seventy-one of the patients
      suffered tricuspid valve dysfunction from rheumatic heart disease. There were 13
      postoperative deaths (within 30 days), giving a mortality rate of 17.8%. The
      actuarial survival at 10 years was 71% +/- 4.2%. Of the survivors, 49 (79.6%)
      were in functional class I or II. Primary tissue valve failure in the tricuspid
      position occurred in 1 patient 12 years after implantation and required
      reoperation. In another patient bioprosthetic tricuspid valve endocarditis
      developed. There was no incidence of thromboembolic complications. We conclude
      that the Ionescu-Shiley pericardial bioprosthesis was a satisfactory prosthesis
      in the tricuspid position in patients with acquired valvar dysfunction.

PMID- 1989532
TI  - Endothelial cell viability in the rat aortic wall.
AB  - Aortic allografts may offer advantages over prosthetic materials for aortic valve
      replacement or reconstruction with a valved aortic conduit. Cellular viability
      may partly determine long-term allograft performance. To evaluate endothelial
      cell viability in a rat model, valved aortic conduits were subjected to
      collagenase digestion. The resulting endothelial cell suspension was labeled with
      Griffonia simplicifolia agglutinin-fluorescein isothiocyanate (GSA-FITC), a
      marker specific for vascular endothelial cells of the rat. The cells were then
      incubated with propidium iodide, which is excluded by viable cells. Flow
      cytometry evaluated endothelial cell viability by determination of percentage of
      GSA-FITC-positive cells that were negative for propidium iodide. Aortas were
      studied immediately after harvest or after storage at 4 degrees C in a nutrient
      medium for 3 to 21 days. Percentage of viable endothelial cells showed a
      progressive decline with increasing duration of storage. These results
      demonstrate flow cytometric measurement of endothelial cell viability, a factor
      of possible importance in assessing allograft storage methods, and show that
      endothelial viability declines with prolonged storage at 4 degrees C in a
      nutrient medium.

PMID- 1989533
TI  - Technique for use of the inferior epigastric artery as a coronary bypass graft.
AB  - A search for a coronary bypass conduit with increased longevity has resulted in
      harvest of the inferior epigastric artery. The artery is dissected through a
      paramedian incision with retraction of the rectus muscle to the lateral side. As
      the inferior epigastric artery courses superiorly, it may lie in one of three
      positions in relation to the rectus muscle. Distal coronary anastomoses using
      this conduit are conventional, and the proximal anastomosis may be made to the
      aorta or end-to-side to an internal mammary artery or venous conduit. After
      preparation with dilute papaverine-Plasmalyte solution proximal sizes have ranged
      from 2.5 to 3.25 mm (internal diameter), and distal inferior epigastric artery
      sizes measured 1.5 to 2.5 mm (internal diameter). The lengths of the conduit
      ranged from 11.5 to 17.0 cm. Eighteen patients aged 41 to 74 years had inferior
      epigastric artery grafts to 19 coronary arteries. The indications for use were
      absent or poor-quality vein, young age with an attempt to limit vein graft, and
      avoidance of use of bilateral internal mammary artery grafts in insulin-dependent
      diabetic patients. There was one sterile wound hematoma and one late wound
      infection. There were no other infections and no deaths. Three patients studied
      postoperatively revealed widely patent inferior epigastric artery grafts.

PMID- 1989535
TI  - Electrocautery does not interfere with the function of the automatic implantable
      cardioverter defibrillator.
AB  - The automatic implantable cardioverter defibrillator (AICD) manufactured by
      Cardiac Pacemakers, Inc, contains an automatic sensitivity adjustment. We tested
      whether this feature would prevent sensing of signals generated by electrocautery
      by implanting three different models of the AICD in 4 mongrel dogs. Unipolar
      electrocautery was applied at maximum output to a site close to the rate-sensing
      leads. The devices were monitored with an AICD-check probe and by auditory
      monitoring of QRS synchronous tones. No sensing of the electrocautery by the
      device occurred. Three patients with two different AICD models (1550 and 1520)
      underwent five surgical procedures in which electrocautery was used. No sensing
      of electrocautery signals, device charging, or other device malfunction occurred.

PMID- 1989534
TI  - Response to chemotherapy does not predict survival after resection of sarcomatous
      pulmonary metastases.
AB  - Between 1979 and 1988, 26 patients with pulmonary metastases from adult soft
      tissue sarcomas were treated with Adriamycin (doxorubicin hydrochloride), Cytoxan
      (cyclophosphamide), and DTIC before metastasectomy. Thirty-eight thoracotomies
      were performed with postoperative complications in 5 patients (5/38, 13.2%) and
      one postoperative death (1/38, 2.6%). Two patients had benign lesions at
      thoracotomy and were excluded from further survival analysis. The median survival
      of the remaining 24 patients after thoracotomy was 18.5 +/- 5.9 months, and the
      actuarial 5-year survival was 22%. Five patients (5/24, 21%) achieved a
      clinically complete response with preoperative chemotherapy, but all had
      recurrence in the lung and underwent resection of pulmonary metastases. Seven
      patients (7/24, 29%) achieved a partial response and had residual disease
      resected at thoracotomy. Twelve patients (12/24, 50%) showed either no change or
      disease progression while receiving chemotherapy and were referred for resection.
      Postthoracotomy disease-free survival and postthoracotomy overall survival did
      not differ significantly between the three groups. One patient in the group
      showing no change or progression of disease while receiving chemotherapy is alive
      without recurrence 57 months after initial pulmonary metastasectomy. Chemotherapy
      can be used for the initial treatment of pulmonary metastases from adult soft
      tissue sarcomas. However, survival after resection of pulmonary metastases cannot
      be accurately predicted based on the clinical response to preoperative
      chemotherapy.

PMID- 1989536
TI  - Long-term results after atrial correction of complete transposition of the great
      arteries.
AB  - This study presents the late results for the first 104 consecutive patients
      surviving and atrial repair for transposition of the great arteries (TGA) between
      January 1971 and December 1978 (group 1). Mean follow-up was 12 years (range, 0.1
      to 17.7 years). The actuarial survival rate at 18 years was 84.2% (70% confidence
      limits, 79% to 88%) for simple TGA and 93.7% (70% confidence limits, 84% to 97%)
      for complex TGA. Nine of the 11 deaths were sudden. Two (2.6%) of the 78 late
      survivors operated on for simple TGA are in New York Heart Association functional
      class III or IV versus 4 (26.7%) of the 15 survivors with complex TGA; the other
      patients are doing very well. To better assess long-term results, we report the
      findings for randomly obtained electrocardiograms, Holter monitor recordings,
      radionuclide angiographic studies, and cardiac catheterizations performed in 1987
      in a larger group of 159 long-term survivors of atrial repair operated on at
      Ospedale Riuniti di Bergamo from January 1971 to December 1984 (group 2), which
      includes all of group 1. The findings confirm that the arterial switch repair is
      the procedure of choice for complex TGA and that there is a major incidence
      (approximately 10%) of systemic right ventricular dysfunction and rhythm
      disturbances after the atrial repair. On the other hand, our late survival rate
      at 18 years of 84% for simple TGA with 97.5% of the patients in functional class
      I is a result that should be kept in mind, especially in institutions where the
      arterial switch is a relatively new approach and presumably is a higher risk to
      cause early death.

PMID- 1989537
TI  - Pulmonary embolectomy: a 20-year experience at one center.
AB  - Between 1968 and 1988, 96 consecutive patients with acute massive pulmonary
      embolism underwent pulmonary embolectomy under cardiopulmonary bypass. The
      operative mortality rate was 37.5%. We analyzed 12 clinical and hemodynamic
      variables by univariate and multivariate analyses to assess the predictive
      factors of postoperative outcome. Multivariate analysis disclosed that cardiac
      arrest and associated cardiopulmonary disease were independent predictors of
      operative death. Long-term follow-up (range, 2 to 144 months; mean, 56 months)
      information was available for 55 of the 60 discharged patients: 6 had died, and 5
      complained of persistent mild or severe exertional dyspnea (New York Heart
      Association class II). These results help assess the preoperative risk in
      patients undergoing pulmonary embolectomy. They also show that, in the few
      patients who do not benefit from optimal medical therapy, pulmonary embolectomy
      remains an acceptable procedure in view of the long-term results.

PMID- 1989538
TI  - When do cerebral emboli appear during open heart operations? A transcranial
      Doppler study.
AB  - The transcranial Doppler technique enabled the detection of cerebral air emboli
      in 10 of 10 patients during open-heart valve operations despite standard deairing
      procedures. With this technique, the occurrence of emboli in the right middle
      cerebral artery was followed continuously in patients undergoing aortic or mitral
      valve replacement. Membrane oxygenators were used. Scattered emboli were observed
      during the insertion of the aortic cannula, at the start of cardiopulmonary
      bypass, and after the declamping of the aorta with the heart beating while empty.
      During the period of aortic cross-clamping, no emboli were detected. Despite
      careful deairing procedures, the recordings indicated a large amount of emboli
      during filling of the empty beating heart in all 10 patients. Thus, this study
      indicates that cerebral emboli in open heart procedures are most likely to occur
      during the redistribution of blood from the heart-lung machine to the patient
      when the heart is beginning to eject actively, despite careful standard deairing
      procedures. Meticulous deairing before declamping the aorta is strongly
      advocated. In addition, a short period of filling of the beating heart before
      final closure of the aortic incision or vent may decrease the incidence of
      cerebral emboli. A concomitant reduction in cerebral blood flow by
      hyperventilation or anesthetics or both during filling of the empty beating heart
      may also be beneficial.

PMID- 1989539
TI  - Intrathoracic fibrin glue for postoperative pleuropulmonary fistula.
AB  - Twenty cases of persistent pleuropulmonary fistula after a thoracic surgical
      procedure were successfully treated with fibrin glue injection into the thoracic
      cavity through a drainage tube. A new technique, the overlying method, which is a
      modification of the conventional technique of fibrin glue injection, was devised.
      Each patient received one to four injections (mean number, 1.6). This method
      resulted in closure of the pleuropulmonary fistula in all but 1 patient. Minor
      complications included pain in 1 patient and fever in 3 patients. A control study
      involving 24 patients with pleuropulmonary fistula was performed. Autoblood, OK
      432, and tetracycline were used instead of fibrin glue. The fistula resolved in
      12 patients. Complications after injection included pain in 15 patients, fever in
      10, and occlusion of the chest tube in 4. With our new method, patients rarely
      exhibited pain and fever, and occlusion of the chest tube did not occur.

PMID- 1989540
TI  - Retrograde continuous warm blood cardioplegia: a new concept in myocardial
      protection.
AB  - This report presents the results in our first clinical series of patients
      receiving continuous warm blood cardioplegia through the coronary sinus. Warm
      oxygenated blood cardioplegia has certain theoretical advantages, such as
      continuously supplying oxygen and substrates to the arrested heart while avoiding
      the side effects of hypothermia. Retrograde infusion of cardioplegia also offers
      certain advantages (eg, in valve operations and in patients with severe coronary
      artery disease) that are complementary to warm blood cardioplegia. Retrograde
      warm blood cardioplegia was used in 113 consecutive patients (85 men and 28 women
      with a mean age of 61 years) undergoing various procedures. Three percent of the
      patients died, 7% needed transient intraaortic balloon pump support, 6% had
      evidence of perioperative myocardial infarction, and 96% had spontaneous return
      of rhythm. There were no coronary sinus injuries. This new technique of
      retrograde continuous warm blood cardioplegia is a simple, safe, and reliable
      method of myocardial protection that may change the way we currently protect the
      heart intraoperatively.

PMID- 1989541
TI  - Coronary pathology predicts conduction disturbances after coronary artery bypass
      grafting.
AB  - Conduction disturbances after coronary artery bypass grafting may result from
      compromised septal blood flow. To examine this hypothesis we reviewed the
      preoperative coronary angiography of 55 consecutive patients undergoing coronary
      artery bypass grafting. Thirty-five patients had either no lesion or a discrete
      lesion in the left anterior descending coronary artery that did not include the
      septal perforator (type I anatomy). Twenty patients had a lesion of the left
      anterior descending coronary artery at the origin of the first septal branch, a
      lesion of the first septal artery, or a pair of lesions in the left anterior
      descending coronary artery that straddled the origin of the first septal artery;
      all lesions were proximal to the graft site (type II anatomy). None of the
      patients with type I anatomy had a major conduction disturbance after coronary
      artery bypass grafting. Eleven of the patients with type II anatomy had major
      conduction disturbances after coronary artery bypass grafting; right bundle
      branch block in 1, right bundle-branch block and left anterior hemiblock in 2,
      left bundle-branch block in 5, and complete atrioventricular block that required
      pacemaker implantation in 3 (p less than 0.001). In the 20 patients with type II
      anatomy, the appearance of conduction disturbances correlated well with the
      absence of retrograde flow to the septal branches from the right coronary artery
      (p less than 0.01). Pathological lesions in the left anterior descending coronary
      artery that compromise flow in the first perforator and that do not provide an
      adequate circulation produce localized damage and conduction disturbances after
      coronary artery bypass grafting. This can be predicted from the preoperative
      angiographic anatomy.

PMID- 1989543
TI  - Potential use of recombinant hirudin as an anticoagulant in a cardiopulmonary
      bypass model.
AB  - Recombinant (r) hirudin is a potent thrombin-specific inhibitor derived from the
      natural hirudin of the leech (Hirudo medicinalis). We have studied the efficacy
      of r-hirudin compared with heparin in a canine model of cardiopulmonary bypass
      operations. Two administration regimens were used for r-hirudin: group 1, 1.0
      mg/kg intracardiac bolus then intravenous bolus at 30 minutes (n = 10); and group
      2, 1.0 mg/kg intracardiac bolus with 1.25 +/- 0.04 mg.kg-1.h-1 intravenous
      infusion (n = 8). Group 3 was given an intracardiac bolus of heparin, 1.66 mg/kg
      (n = 9). Aspiration of blood from the chest cavity revealed no significant
      difference between the three groups. Measurement of fibrin deposits in the pump
      line filter revealed higher amounts in the r-hirudin groups (p = 0.02). Decreases
      in platelets, fibrinogen, and hematocrit due primarily to hemodilution were the
      same in each group. The bleeding time assay showed less prolongation for r
      hirudin than for heparin (p less than 0.001). No antagonist for r-hirudin was
      used; however, due to its short half-life all coagulation variables returned to
      baseline within 30 minutes after cardiopulmonary bypass. Because r-hirudin lacks
      effect on platelets, is a poor immunogen, does not require a plasma cofactor, and
      may not require an antagonist, it may provide an alternative anticoagulant to
      heparin in cardiopulmonary bypass. Additional studies are, however, needed to
      optimize the dose and to evaluate other clinical aspects of r-hirudin.

PMID- 1989542
TI  - Dopamine and high-dose insulin infusion (glucose-insulin-potassium) after a
      cardiac operation: effects on myocardial metabolism.
AB  - Myocardial insulin resistance, in association with surgical stress, restricts the
      availability of carbohydrates and increases the load of free fatty acids (FFAs)
      on the heart. On theoretical grounds adrenergic drugs may be expected to
      aggravate this situation, whereas the opposite is expected from insulin. The
      influence of dopamine and a combination of dopamine (7 micrograms/kg body
      weight/min) and high-dose insulin (7 IU/kg) on myocardial energy metabolism was
      studied in 19 patients 4 to 6 hours after a coronary operation. Infusion of
      dopamine (7 micrograms/kg body weight/min) induced metabolic changes that may be
      unfavorable to the strained myocardium. There was an increase of the myocardial
      FFA load and a rise in myocardial oxygen expenditure by 60% to 70%. There changes
      were, however, not matched by an increase in myocardial substrate uptake. "Oxygen
      wastage" of FFA metabolism at high circulating catecholamine levels is suggested.
      There were also signs suggesting an amplified systemic trauma response: systemic
      oxygen consumption increased by 15%, and an increase in the arterial levels of
      FFAs, glucose, and ketones was observed. Divergent metabolic effects of dopamine
      and insulin were demonstrated. The most prominent metabolic effects of adding
      high-dose insulin to dopamine were a marked reduction of arterial FFA levels and
      a shift toward myocardial carbohydrate utilization at the expense of FFAs.
      Myocardial uptake of FFAs ceased. Myocardial insulin resistance may thus to a
      significant extent be overcome by supraphysiological doses of insulin, even
      during infusion of adrenergic drugs.

PMID- 1989544
TI  - Optimizing myocardial hypothermia: I. Temperature probe design and clinical
      inferences.
AB  - Myocardial hypothermia is an essential component of myocardial preservation for
      most cardiac operations. Because of multiple causes of rewarming, it is necessary
      to monitor temperatures at specific sites (right and left ventricular epicardium
      and endocardium or cavity). Thus, plastic temperature probes have been designed
      and fabricated to facilitate temperature monitoring at these sites. Using a bare
      thermocouple as a standard, in vitro comparison of metallic probes and plastic
      probes revealed differences of 4.0 degrees +/- 0.9 degrees C and 0.7 degrees +/-
      0.6 degrees C, respectively (p less than 0.005). Consequently, metallic probes do
      not have sufficient accuracy to detect transmural temperature gradients because
      of "stem effect." Using the plastic probes to evaluate temperature changes in
      porcine hearts after cardioplegia-induced hypothermia revealed a temperature rise
      of 1 degree C/min at all sites if control of systemic and venous return and local
      myocardial cooling are not provided. The use of temperature monitoring at
      multiple sites permits identification and prevention of various causes of
      myocardial rewarming and is facilitated by the use of plastic probes described
      herein which contain dual thermocouples.

PMID- 1989545
TI  - Optimizing myocardial hypothermia: II. Cooling jacket modifications and clinical
      results.
AB  - After induction of myocardial hypothermia by cold cardioplegic solution,
      myocardial rewarming occurs at 0.5 degrees to 1.0 degrees C/min. In addition to
      preventing myocardial rewarming from systemic and pulmonary venous return,
      continuous cooling of the myocardial surface must be provided. Modifications of a
      previously reported cooling jacket are described. These modifications include
      decreased width and thickness of the metal skeleton for easier application and
      increased malleability, respectively. Also, the double-row flow channel markedly
      minimizes obstruction of flow secondary to kinking and allows inlet and outlet
      lines to attach at adjacent points of the jacket thus minimizing obstruction of
      the operative field. The effectiveness of the jacket in 36 patients undergoing
      valve replacement and 19 patients having pulmonary thromboendarterectomy was
      evaluated by measurement of myocardial temperatures at multiple sites throughout
      aortic cross-clamping. Temperatures at all sites were maintained at 12 degrees C
      or less. Temperatures measured in phrenic nerve pedicles ranged from 25 degrees
      to 27 degrees C. During cooling, heat removal by the jacket was 330 calories/min.
      During maintenance of myocardial hypothermia, heat flow was 190 calories/min.
      Modifications of a cooling jacket facilitate usability and an array of sizes
      enhances applicability.

PMID- 1989546
TI  - Diagnosis of poststernotomy infection: comparison of three means of assessment.
AB  - Of 737 adults undergoing cardiac operations through a median sternotomy over a 2
      year period (January 1988 to January 1990), sternal-substernal space infection
      requiring mediastinal exploration developed in 8. Six of these patients as well
      as 18 additional patients were evaluated for possible poststernotomy wound
      infection by computed tomography (4 true positive, 4 false positive, 10 true
      negative, 2 false negative), indium-111 leukocyte scanning (5 true positive, 0
      false positive, 18 true negative, 1 false negative), and epicardial pacer wire
      cultures (6 true positive, 1 false positive, 12 true negative, 0 false negative).
      On the basis of this experience it is suggested that in addition to computed
      tomography, indium-111 leukocyte scanning and epicardial pacer wire cultures may
      be useful in the diagnosis of poststernotomy deep wound infection.

PMID- 1989547
TI  - Combined superior-transseptal approach to the left atrium.
AB  - The combined superior-transseptal approach to the left atrium was used in 22
      patients: to perform a mitral valve repair in 14 patients and mitral valve
      replacement in 8 patients. Mitral valve operation was combined with other cardiac
      procedures in 18 patients (82%) and was performed as a reoperation in 3 patients
      (14%). In all cases there was excellent exposure of the complete mitral annulus
      and subvalvar apparatus. There were no instances of postoperative bleeding,
      conduction defects, or intraatrial shunting related to the approach. The combined
      superior-transseptal approach to the left atrium is an excellent approach that
      can be used in most reoperations and primary procedures for isolated or combined
      mitral valve operations.

PMID- 1989548
TI  - Late volume changes in retrosternal colon bypass.
AB  - Esophageal obstruction by malignancy, chemical burns, or other less common
      entities presents a challenge for the surgeon. Either for esophageal substitution
      after esophageal resection or as a bypass for the obstructed esophagus, colon
      interposition is often the best available option. Massive colonic enlargement
      requiring resection of the interposed dilated colon developed recently in 2 of
      our patients who had a colon bypass 22 and 10 years earlier, respectively.

PMID- 1989549
TI  - Misplaced caval filter and subsequent pericardial tamponade.
AB  - Use of the Greenfield filter for partial caval interruption is generally accepted
      as the most reliable mechanical method of pulmonary embolus prophylaxis. However,
      there have been reports of a variety of (usually nonfatal) complications. We
      report here the near-fatal complication of acute pericardial tamponade after
      misplacement of a Greenfield filter. Because of the filter's unusual location,
      retrieval required cardiopulmonary bypass, profound hyperthermia, and circulatory
      arrest.

PMID- 1989550
TI  - Total unilateral lung gangrene in Hodgkin's disease: treatment by thoracostomy.
AB  - Total gangrene of the left lung developed in a 30-year-old male patient with a
      pulmonary recurrence of Hodgkin's disease after mediastinal irradiation and
      chemotherapy. Clinically, tension pyopneumothorax and severe septic shock were
      present. Surgical repair was done by thoracostomy, resecting three ribs. A 2 x
      0.5-cm hole in the necrotic wall of the left main bronchus was covered with an
      intercostal muscle bundle. The necrotic pleural surfaces were treated openly by
      daily change of dressings. The patient recovered satisfactorily and underwent
      four further courses of chemotherapy without any complications.

PMID- 1989551
TI  - Intraoperative management of severe endobronchial hemorrhage.
AB  - Endobronchial hemorrhage due to pulmonary artery perforation by a Swan-Ganz
      catheter developed during coronary artery bypass grafting while weaning from
      cardiopulmonary bypass. After reinstitution of cardio-pulmonary bypass with
      pulmonary artery venting, bleeding was localized to the right lower lobe bronchus
      using fiberoptic bronchoscopy. A Fogarty embolectomy catheter was inflated in the
      bronchus to tamponade successfully only the right lower lobe. This case
      illustrates a method of distal bronchial blockade for maximal retention of
      pulmonary function and avoidance of pulmonary resection.

PMID- 1989552
TI  - Nephrotic syndrome complicating adenocarcinoma of the lung with resolution after
      resection.
AB  - Nephrotic syndrome is an uncommon complication of lung cancer. We present a case
      in which adenocarcinoma was complicated by the nephrotic syndrome, which resolved
      after resection of the cancer.

PMID- 1989553
TI  - Transesophageal echocardiography in acute aortic transection.
AB  - Confirming the diagnosis of acute transection of the descending aorta can be
      problematic. Unnecessary patient movement and time delay are often associated
      with conventional investigations. We describe a patient in whom such an injury
      was clearly and quickly defined at the bedside by transesophageal
      echocardiography.

PMID- 1989554
TI  - Aortic atresia with normal left ventricle: one-stage repair in early infancy.
AB  - Successful one-stage repair of aortic atresia with a left ventricle was performed
      in a 6-week-old infant using a new technique. After patch enhancement of the
      hypoplastic aortic arch, the transected proximal pulmonary artery was directly
      anastomosed to the aortic arch. An intraventricular baffle established continuity
      between the left ventricle and neoaortic valve, and a homograft conduit was
      inserted between the right ventricle and pulmonary artery bifurcation.

PMID- 1989555
TI  - Intraoperative echocardiography of a dislodged Bjork-Shiley mitral valve disc.
AB  - The successful management of a patient who suffered an outlet strut fracture of a
      Bjork-Shiley 60-degree convexo-concave mitral valve prosthesis is reported.
      Emergency operation was life-saving. Preoperative echocardiography assisted in
      making a prompt diagnosis, and intraoperative echocardiography allowed the
      detection and removal of the dislodged disc from the left ventricle at the time
      of the operation. The role of intraoperative echocardiography in the diagnosis of
      prosthetic strut fracture is emphasized.

PMID- 1989556
TI  - Delayed death from aortic root trauma.
AB  - A 40-year-old man suffered blunt chest trauma, had a myocardial infarct 58 days
      later, and died unexpectedly 19 days after that. Autopsy showed partial avulsion
      of a small branch of the right coronary artery with thrombus extending into the
      right coronary sinus of Valsalva occluding the right coronary artery and causing
      a myocardial infarct. Death was caused by a thromboembolus arising from the
      aortic root thrombus and occluding the left main coronary artery. The case is
      unusual in that the major consequences of the aortic root trauma were delayed,
      and death resulted from occlusion of both coronary arteries.

PMID- 1989557
TI  - Tricuspid valve incompetence caused by nonpenetrating thoracic trauma.
AB  - Tricuspid valve incompetence from ruptured papillary muscle or chordae as a
      result of nonpenetrating trauma is uncommon. Blunt trauma causing partial
      detachment of a leaflet from the annulus is very rare. We report the case of a
      young adult involved in a car accident who had these findings. Operative repair
      with resuture of the leaflet to the annulus and annuloplasty using a Carpentier
      ring resulted in complete recovery.

PMID- 1989558
TI  - Exchanging double-lumen for single-lumen endotracheal tubes after thoracotomy.

PMID- 1989559
TI  - Easy removal of surgically placed intraaortic balloon pump catheter.

PMID- 1989560
TI  - Improved technique for inserting a T tube in patients with subglottic stenosis.
AB  - An improved method for inserting a silicone T tube through a tracheostomy stoma
      in patients with subglottic stenosis is presented. A silicone T tube is pulled
      into the trachea with a catheter that is inserted into the tracheostomy stoma,
      advanced through the stenotic subglottic space, and pulled out the mouth. A cone
      shaped dilator is placed beforehand at the proximal end of the vertical limb of
      the T tube to facilitate the passage of that end through the stenotic subglottic
      space. This method was used in 4 patients with good results. We suggest this
      technique be tried when attempts to insert a T tube by the usual method fail, as
      it can be performed under local anesthesia without special instruments and is
      technically easy.

PMID- 1989561
TI  - Apical aortic cannulation: application of an old method with new paraphernalia.
AB  - An instrument assembly consisting of a special aortic cross-clamp and double
      lumen perfusion cannula is presented. The application of these instruments allows
      occlusion of the ascending aorta traversed by the perfusion cannula inserted
      directly or through the apex of the heart as well as simultaneous left
      ventricular venting.

PMID- 1989562
TI  - The Starr valve revisited.

PMID- 1989563
TI  - Bronchoalveolar lavage in lung transplantation.
AB  - One of the dilemmas in the management of lung allotransplant recipients is our
      inability to precisely determine the cause of graft dysfunction. Differentiating
      between lung allograft infection, rejection, atelectasis, or ischemic injury
      remains a difficult task. Tests directed at identifying systemic abnormalities
      such as peripheral blood analysis so far have been nonspecific and unlikely to
      accurately and promptly represent changes occurring within the lungs.
      Transbronchial biopsy and bronchoalveolar lavage have emerged as two methods with
      the most potential for aiding in the establishment of diagnosis. This review
      attempts to provide the readers with a current knowledge of the cellular events
      in lung allograft and the status of bronchoalveolar lavage in experimental and
      clinical lung transplantation.

PMID- 1989564
TI  - Human immunodeficiency virus and the thoracic surgeon.

PMID- 1989565
TI  - Staging lung cancer with computed tomography.

PMID- 1989566
TI  - Single drain (pleura, pericardium, mediastinum) after open heart operations.

PMID- 1989567
TI  - Congenital bronchoesophageal fistula.

PMID- 1989568
TI  - Uncomfortable issues.

PMID- 1989569
TI  - Coronary artery bypass grafting in patients with calcified aorta.

PMID- 1989570
TI  - Effectiveness of psychoeducational interventions in reducing emotional distress
      after human immunodeficiency virus antibody testing.
AB  - To examine the effectiveness of three psychoeducational interventions in reducing
      emotional distress after voluntary serologic testing for human immunodeficiency
      virus-1,307 physically asymptomatic adults were randomly assigned to standard
      counseling, counseling plus a three-session interactive video program, or
      counseling plus six individual sessions of stress prevention training. Subjects
      were evaluated using five standardized distress measures at entry and 3 months
      later. Among the 204 human immunodeficiency virus-seronegative subjects, mean
      distress measures decreased significantly after all three interventions without
      differential treatment effects. Among the 103 human immunodeficiency virus
      seropositive subjects, mean distress measures decreased significantly after the
      stress prevention training and did not significantly increase in the other two
      interventions. We conclude that stress prevention training is particularly
      helpful after notification of human immunodeficiency virus seropositivity.

PMID- 1989571
TI  - Blunted growth hormone response to clonidine in patients with generalized anxiety
      disorder.
AB  - Patients with panic disorder or depression have abnormal responses to the alpha 2
      adrenergic receptor partial agonist clonidine. Evidence linking anxiety to
      noradrenergic dysfunction and the presence of anxiety symptoms in both depression
      and panic suggest that abnormal responses to clonidine in these disorders could
      be due to the anxiety symptoms. To explore a possible link between "nonspecific"
      anxiety symptoms and abnormal responses to clonidine, patients with DSM-III
      defined generalized anxiety disorder were given intravenous infusions of
      clonidine hydrochloride. Responses of plasma growth hormone, 3-methoxy-4
      hydroxyphenylglycol, heart rate, blood pressure, and psychological states were
      determined in 11 patients with generalized anxiety disorder and 14 healthy
      subjects. Clonidine produced significantly smaller growth hormone responses in
      patients than in healthy controls. The two groups did not differ in 3-methoxy-4
      hydroxyphenylglycol, heart rate, blood pressure, or psychological responses to
      clonidine. These results are compared with data from similar studies on patients
      with panic disorder and depression. The blunting of the growth hormone response
      to clonidine in all three disorders could be due to the presence of generalized
      anxiety symptoms. Subsensitivity of postsynaptic alpha 2-adrenoreceptors may be
      present in all three disorders; however, there are alternative interpretations of
      growth hormone blunting in response to clonidine. Blunting was observed in DSM
      III-defined generalized anxiety disorder, whether or not the DSM-III-R criterion
      of excessive worry was also present.

PMID- 1989572
TI  - Dosage of haloperidol for schizophrenia.
AB  - Eighty-seven newly admitted inpatients with schizophrenia were randomized to
      receive 10, 30, or 80 mg/d of oral haloperidol. They were treated under double
      blind conditions for 6 weeks, less if their acute symptoms remitted sooner.
      Survival analysis showed no differences among the three treatments. Side effects
      were minimal in all three treatment groups, and there were no differences in side
      effects among the groups. These results suggest that dosages higher than 10 mg/d
      of haloperidol for most patients have no additional beneficial effect in the
      treatment of acute or exacerbated schizophrenia.

PMID- 1989574
TI  - Substance abuse among subjects seeking treatment for alcoholism.

PMID- 1989573
TI  - Cerebral size affects localized density measured by computed tomography.

PMID- 1989575
TI  - Synthesis of phosphatidylethanolamine and ethanolamine plasmalogen by the CDP
      ethanolamine and decarboxylase pathways in rat heart, kidney and liver.
AB  - Studies with mammalian cell lines have led to suggestions that mammalian tissues
      may derive all of their phosphatidylethanolamine (PE) from the decarboxylation of
      phosphatidylserine (PS), and also that the physiological significance of the CDP
      ethanolamine pathway was the synthesis of ethanolamine plasmalogen. We have
      therefore investigated the biosynthesis of PE and ethanolamine plasmalogen via
      the CDP-ethanolamine and decarboxylation pathways in vivo in three rat tissues
      (heart, kidney and liver), which differ in ethanolamine plasmalogen content. In
      all three tissues [14C]ethanolamine was incorporated into both PE and
      ethanolamine plasmalogen, whereas [3H]serine was incorporated into only PS and PE
      fractions. When [14C]ethanolamine was introduced into the animals, the specific
      radioactivity of ethanolamine plasmalogen in the kidney was always greater than
      that of the PE fraction; in the heart the specific radioactivity of the
      ethanolamine plasmalogen fraction was similar to that of the PE fraction, whereas
      in the liver the specific radioactivity of the PE fraction was always greater
      than that of the ethanolamine plasmalogen fraction. The results obtained in this
      study indicate that: (1) the CDP-ethanolamine pathway is utilized for the
      synthesis of both PE and ethanolamine plasmalogen in all three tissues; (2) the
      decarboxylation pathway is utilized solely for the synthesis of PE; (3) serine
      plasmalogens are not formed by base-exchange reactions; (4) the relative
      utilization of the CDP-ethanolamine pathway for the synthesis of PE and
      ethanolamine plasmalogen varies among tissues. Our studies also revealed that the
      hypolipidaemic drug MDL 29350 is a potent inhibitor of PE N-methyltransferase
      activity in vitro and in vivo.

PMID- 1989576
TI  - Inhibition of proteolysis in the liver by chronic ethanol feeding.
AB  - Effects of chronic ethanol feeding on the volume density of lysosomes, the rate
      of protein degradation and the amount of protein were studied in livers perfused
      in situ at 07:00, 11:00, 17:00 and 23:00 h. Ethanol was given to the rats in
      drinking water for either 3 or 8-10 weeks. During week 3 of treatment and
      onwards, the average daily consumption of ethanol was 12.3 +/- 0.3 g/kg body wt.
      Morphometric analysis revealed that the volume density of autophagosomes and
      autolysosomes was lower in the ethanol-fed rats than in the controls. When
      compared with age-matched controls, the rate of proteolysis, measured as release
      of valine, was 33% and 26% less in the ethanol-fed rats after treatment for 3 and
      8-10 weeks respectively. The difference between the two groups was most
      pronounced at 07:00 and 11:00 h. Protein content of the liver increased
      significantly after the longer ethanol treatment. According to these results,
      chronic ethanol feeding inhibits proteolysis in the liver by preventing the
      sequestration of protein into lysosomes.

PMID- 1989577
TI  - Effects of taurolithocholate, a Ca2(+)-mobilizing agent, on cell Ca2(+) in rat
      hepatocytes, human platelets and neuroblastoma NG108-15 cell line.
AB  - The monohydroxy bile acid taurolithocholate permeabilizes the endoplasmic
      reticulum to Ca2+ in rat liver cells. To assess whether this action on the
      endoplasmic reticulum was restricted to this tissue, the effects of bile acid
      were investigated in two cell types quite unrelated to rat hepatocyte, namely
      human platelets and neuronal NG108-15 cell line. The results showed that
      taurolithocholate (3-100 microM) had no effect on free cytosolic [Ca2+] in human
      platelets and NG108-15 cells. whereas it increased it from 180 to 520 nM in rat
      hepatocytes. In contrast, in cells permeabilized by saponin, taurolithocholate
      initiated a profound release of the stored Ca2+ from the internal Ca2+ pools in
      the three cell types. The bile acid released 90% of the Ca2+ pools, with rate
      constants of about 5 min-1 and half-maximal effects at 15-30 microM. The results
      also showed that, in contrast with liver cells, which displayed an influx of
      [14C]taurolithocholate of 2 nmol/min per mg, human platelets and the neuronal
      cell line appeared to be resistant to [14C]taurolithocholate uptake. The influx
      measured in these latter cells was about 100-fold lower than in rat liver cells.
      Taken together, these data suggest that human platelets and NG108-15 cells do not
      possess the transport system for concentrating monohydroxy bile acids into cells.
      However, they show that human platelets and neuronal NG108-15 possess, in common
      with liver cells, the intracellular system responsible for taurolithocholate
      mediated Ca2+ release from internal stores.

PMID- 1989578
TI  - Some properties of duck gizzard caldesmon.
AB  - The domain structure of duck gizzard caldesmon was investigated. A single thiol
      group is located in the vicinity of the C-terminus of the protein. A simple
      method for the purification of a short (21 kDa) C-terminal peptide formed after
      chemical cleavage of caldesmon at cysteine residues was evolved. The C-terminal
      peptide of caldesmon interacts with calmodulin with an affinity one order of
      magnitude higher than that of native caldesmon. The Ca2+/phospholipid-dependent
      protein kinase (protein kinase C) transfers about 2 mol of phosphate per mol of
      caldesmon. All sites phosphorylated by protein kinase C are located in the short
      (21 kDa) C-terminal peptide of caldesmon. Phosphorylation does not affect the
      interaction of caldesmon with calmodulin.

PMID- 1989579
TI  - Abundance of hepatic metallothionein mRNA is increased by protein-synthesis
      inhibitors. Evidence for transcriptional activation and post-transcriptional
      regulation.
AB  - Ongoing protein synthesis is a prerequisite in the expression of some genes. We
      studied the effect of various protein synthesis inhibitors on the expression of
      the avian metallothionein (MT) gene. Chicken embryonic hepatocytes in culture
      were exposed to various concentrations of cycloheximide, puromycin and
      pactamycin. At concentrations which decreased total protein synthesis by about
      90% each inhibitor increased MT mRNA accumulation approx. 5-fold at 9 h of
      incubation. Incubation with puromycin or zinc for 2 h markedly increased the rate
      of MT gene transcription. Estimates of the half-life of MT mRNA by using
      actinomycin D suggested for cycloheximide, but not puromycin, decreased the decay
      rate of MT mRNA. These data suggest the potential for post-transcriptional
      regulation of the avian MT gene. We conclude that different antibiotics increase
      the accumulation of hepatocyte MT mRNA by different mechanisms and that the
      possibility of multiple mechanisms should be considered in other studies of the
      role of protein synthesis in gene expression.

PMID- 1989581
TI  - L-lactate uptake by rat liver. Effect of food deprivation and substrate
      availability.
AB  - We have studied the role of substrate availability on net L-lactate uptake by
      liver of anaesthetized fed and 24 h-fasted rats. L-Lactate was infused through a
      mesenteric vein at infusion rates equivalent to 0, 0.125, 0.25 and 0.5 times the
      basal turnover rate (Rt). By these means we were able to increase L-lactate
      portal concentrations up to 5.5 mM, without significant changes in portal pH. In
      the basal state (0 Rt), a net L-lactate uptake by liver was found in 24 h-fasted
      animals. No net balance was observed in fed rats. Infusion of L-lactate in fed
      animals failed to induce a net hepatic uptake, except when L-lactate levels in
      portal vein were raised above 5 mM. In fasted animals, net L-lactate uptake by
      liver increased linearly (r = 0.99) as a function of L-lactate concentration in
      the portal vein, even beyond the saturation of its specific carrier. It is
      concluded that, first, the L-lactate carrier does not limit net L-lactate uptake,
      and second, that substrate availability is an important factor modulating net L
      lactate uptake by liver.

PMID- 1989580
TI  - Stimulation of phosphatidylcholine synthesis by activators of protein kinase C is
      dissociable from increased phospholipid hydrolysis.
AB  - The aim of this study was to clarify the relationship between the stimulatory
      effects of protein kinase C activators, including phorbol 12-myristate 13-acetate
      (PMA) and bryostatin, on the hydrolysis of phosphatidylcholine (PtdCho) and
      phosphatidylethanolamine (PtdEtn) and on PtdCho synthesis. The cell lines used
      were selected because of their differential responses to protein kinase C
      activators and included rat-1 fibroblasts, untransformed and A-raf-transformed
      NIH 3T3 fibroblasts and human HL60 leukaemia cells. Exposure of rat-1 and NIH 3T3
      fibroblasts to 100 nM-PMA stimulated phospholipase D-mediated hydrolysis of
      phospholipids about 2- and 6-fold respectively. In contrast, 100 nM-PMA had
      similar (2.5-3.0-fold) stimulatory effects on PtdCho synthesis in these cell
      lines. In the untransformed NIH 3T3 cells, both PMA and bryostatin stimulated
      both phospholipid hydrolysis and PtdCho synthesis, with 100 nM-bryostatin being
      somewhat less potent than 100 nM-TPA. In contrast, in A-raf-transformed NIH 3T3
      cells or in HL60 cells, only TPA, but not bryostatin, stimulated PtdCho
      synthesis. In these transformed cells, bryostatin had 3-fold, or higher,
      stimulatory effects on phospholipid hydrolysis. Addition of ionomycin, a Ca2(+)
      elevating agent, partially restored the stimulatory effect of bryostatin on
      PtdCho synthesis, but it failed to modify the effect of bryostatin on
      phospholipid hydrolysis. These data indicate that increased phospholipid
      hydrolysis is not necessarily associated with increased PtdCho synthesis.

PMID- 1989582
TI  - Products and intermediates of the beta-oxidation of [U-14C]hexadecanedionoyl-mono
      CoA by rat liver peroxisomes and mitochondria.
AB  - 1. The synthesis of [U-14C]hexadecanedionoyl-mono-CoA is described. 2. The beta
      oxidation of [U-14C]hexadecanedionoyl-mono-CoA by purified rat liver peroxisomes
      and mitochondria is demonstrated. 3. The products of mitochondrial beta-oxidation
      of [U-14C]hexadecanedionoyl-mono-CoA include ketone bodies, citrate and
      acetylcarnitine. 4. Tetradecadionoyl-mono-CoA, hexadec-2-enedionyl-mono-CoA and
      hexadionoyl-mono-CoA were the only detectable intermediates formed by
      mitochondrial beta-oxidation, whereas acetyl-CoA and all saturated even-numbered
      intermediates of chain length C6-C16 were generated by peroxisomal beta
      oxidation. 5. Hexadecanedionoyl-mono-CoA and hexadecanoyl-CoA were equally
      effective substrates for peroxisomal beta-oxidation, but hexadecanedionoyl-mono
      CoA was a relatively poorer substrate for the mitochondrial pathway.

PMID- 1989584
TI  - A three-disulphide derivative of hen lysozyme. Structure, dynamics and stability.
AB  - A three-disulphide derivative of hen egg-white lysozyme was made by selective
      reduction and carboxymethylation of one of the four original disulphide bridges.
      N-Terminal sequencing and two-dimensional 1H-n.m.r. spectroscopy revealed that
      the disulphide bridge linking cysteine residues 6 and 127 had been modified and
      that the three remaining disulphide bonds were native-like in nature. Analysis of
      COSY and NOESY spectra indicated that the three-disulphide lysozyme (CM6.127
      lysozyme retains the same secondary and tertiary structure as its four-disulphide
      counterpart; its stability to pH and temperature is, however, dramatically
      decreased. N.m.r. spectroscopy was used to characterize the thermal folding and
      unfolding transition of CM6.127-lysozyme. Not only is the transition still a
      highly co-operative event, but the enthalpy change associated with folding and
      unfolding resembles that of intact lysozyme when their differences in thermal
      stability are taken into consideration. The significance of these results in
      terms of the folding process of lysozyme is discussed. By contrast with authentic
      lysozyme, CM6.127-lysozyme was found to exist in an unfolded state at pH 2 at
      room temperature. N.m.r. spectroscopy and c.d. were used to characterize this
      state. Unlike their homologous relative, alpha-lactalbumin, which exists in a
      partially folded molten globule state under these conditions, only residual non
      native-like structure persists in the acid-unfolded state of CM6.127-lysozyme.
      These results indicate that the difference in folding behaviour of lysozyme and
      alpha-lactalbumin cannot be accounted for simply by their differences in thermal
      stability.

PMID- 1989586
TI  - Glucose utilization by interscapular brown adipose tissue in vivo during
      nutritional transitions in the rat.
AB  - Glucose utilization indices (GUI) of interscapular brown adipose tissue (IBAT)
      declined by 84% after 48 h starvation. Two-thirds of the overall response was
      observed within 6 h, correlating with decreased insulin concentrations. Re
      feeding 48 h-starved rats restored insulin concentrations and evoked a rapid 15
      fold increase in IBAT GUI. GUI values after re-feeding were markedly higher than
      those observed at equivalent insulin concentrations in control post-absorptive
      rats.

PMID- 1989587
TI  - Heterogeneity of serum amyloid A with respect to molecular mass.

PMID- 1989585
TI  - Changes in the mechanism of Ca2(+) mobilization during the differentiation of
      BC3H1 muscle cells.
AB  - Ca2+ sequestration and release in BC3H1 muscle cells is strongly dependent on the
      stage of differentiation. In proliferating cells, more than 90% of the
      sequestered Ca2+ was Ins(1,4,5)P3-sensitive and 25% was caffeine-sensitive. In
      differentiated cells, the Ca2+ accumulation was 5-fold higher and was InsP3
      insensitive, but about 60% of the sequestered Ca2+ was caffeine-sensitive. These
      changes were reversible upon addition of growth stimuli. Similarly, by measuring
      the intracellular Ca2+ concentration in single intact BC3H1 cells, it was found
      that the number of histamine-responsive cells decreased and the number of
      caffeine-responsive cells increased during muscle cell differentiation. These
      data indicate that the development of the muscle phenotype in BC3H1 myoblasts
      induces a major rearrangement of the mechanisms for Ca2+ mobilization.

PMID- 1989588
TI  - The alternative pathway of haem synthesis via dehydroisocoproporphyrinogen in
      mutants of Saccharomyces cerevisiae partially deficient in uroporphyrinogen
      decarboxylase activity.

PMID- 1989589
TI  - Comparison of the effects of various amino acids on glycogen synthesis,
      lipogenesis and ketogenesis in isolated rat hepatocytes.
AB  - Several amino acids were found to stimulate glycogen synthesis and lipogenesis,
      and to inhibit ketogenesis in isolated rat hepatocytes. When hepatocytes were
      incubated in the presence of 20 mM-glucose, the amino acids could be classified
      in decreasing order of efficiency as follows: glutamine and proline, alanine,
      aminoisobutyric acid, asparagine and histidine for stimulation of glycogen
      synthesis; glutamine, proline and alanine for stimulation of lipogenesis; proline
      and glutamine for inhibition of ketogenesis. The study of the time course
      revealed that the rates were not linear and were preceded by a lag period. In all
      conditions studied, glutamine and proline were found to have similar quantitative
      effects on glycogen synthesis and lipid metabolism. However, their effects differ
      qualitatively. Indeed, the effects of proline on glycogen synthesis, lipogenesis
      and glutamate and aspartate content were faster. Moreover, proline increased the
      hydroxybutyrate/acetoacetate ratio, whereas glutamine did not change it.
      Incubation of hepatocytes with aminoisobutyric acid or under hypo-osmotic
      conditions, which increased cell volume and mimicked the amino acid-induced
      stimulation of glycogen synthesis, had little effect on lipogenesis. In
      hepatocytes incubated without glucose, ketogenesis was inhibited, in decreasing
      order of efficiency, by alanine, asparagine, glutamine and proline. Under these
      conditions, glutamine increased, alanine decreased and asparagine did not affect
      the concentration of malonyl-CoA. This indicates that the latter cannot be
      responsible for the inhibition of ketogenesis by alanine and asparagine.

PMID- 1989590
TI  - Inactivation of the RTEM-1 cysteine beta-lactamase by iodoacetate. The nature of
      active-site functional groups and comparisons with the native enzyme.
AB  - The pH-rate profile for inactivation of the RTEM-1 cysteine beta-lactamase by
      iodoacetate supports previous evidence [Knap & Pratt (1989) Proteins Struct.
      Funct. Genet. 6, 316-323] for the activation of the active-site thiol group by
      adjacent functional groups. The enhanced reactivity of iodoacetate, with respect
      to that of iodoacetamide, suggests the influence of a positive charge in the
      active site. The reactivity of iodoacetate is not affected by dissociation of an
      active-site functional group of pKa 6.7, which increases the reactivity of
      neutral reagents, probably because of a compensation phenomenon; it is, however,
      lost on dissociation of an acid of pKa 8.1. It is concluded that the active
      cysteine beta-lactamase has four functional groups at the active site, one
      nucleophilic thiolate of Cys-70, one neutral acid (most probably the carboxy
      group of Glu-166, from the crystal structures) and two cationic residues (most
      probably Lys-73 and Lys-234). A comparison of these results with the pH
      dependence of reactivity of the native RTEM-2 beta-lactamase suggests that the
      active form of the latter enzyme is also monocationic, although the nucleophile
      (Ser-70) is likely to be neutral in this case and the carboxylic acid
      dissociated. A mechanism of class A beta-lactamase catalysis is discussed where
      the Glu-166 carboxylate acts as a general base/acid catalyst and Lys-73 is
      principally required for electrostatic stabilization of the anionic tetrahedral
      intermediate.

PMID- 1989591
TI  - Effects of dexamethasone on lung protein turnover.
AB  - Dexamethasone (2.5 mg/day per kg) treatment of young growing rats resulted in
      reduced food intake and rapidly inhibited whole-body and lung growth. Although
      the reduction in food intake partially explained the decrease in whole-body
      growth, it did not influence lung growth. After 24 h of dexamethasone treatment,
      ribosomal efficiency in the lung was reduced 44%, producing a 38% decrease in the
      rate of pulmonary protein synthesis. Extending dexamethasone treatment to 5 days
      resulted in decreases in both ribosomal efficiency (35%) and capacity (28%),
      explaining the 53% reduction in lung protein synthesis at this time. After both
      the acute and chronic steroid regimes, the decreased rates of pulmonary protein
      synthesis were accompanied by a loss of polyribosomes and an elevated ribosomal
      monomer pool, indicating that dexamethasone blocked translation at the site of
      peptide-chain initiation.

PMID- 1989593
TI  - 1,25 (OH)2 vitamin D3 attenuates the loss of resistance artery contractile
      function associated with incubation in culture media.
AB  - Contractile properties of rat mesenteric resistance arteries were studied
      immediately after isolation or after 48-hr incubation in culture medium
      [Dulbecco's modified Eagle's/Ham's F-12 (1:1) with insulin, transferrin and
      antibiotics]. Incubation in culture medium depressed active stress generating
      capacity, increased sensitivity to norepinephrine and ablated endothelium
      dependent relaxation. The decrease in stress generation results from the loss of
      a releasable pool of intracellular Ca2+; the enhanced sensitivity is associated
      with decreased neuronal amine pump function. Addition of 300 pg/ml 1,25 (OH)2
      vitamin D3 to the culture medium afforded nearly complete protection against the
      loss of stress generating capacity and partially preserved endothelial function.
      It is concluded that 1,25 (OH)2 vitamin D3 partially prevents phenotypic
      modulation of the vascular myocyte induced by culture conditions.

PMID- 1989592
TI  - Comparison of benzyl alcohol dehydrogenases and benzaldehyde dehydrogenases from
      the benzyl alcohol and mandelate pathways in Acinetobacter calcoaceticus and from
      the TOL-plasmid-encoded toluene pathway in Pseudomonas putida. N-terminal amino
      acid sequences, amino acid compositions and immunological cross-reactions.
AB  - 1. N-Terminal sequences were determined for benzyl alcohol dehydrogenase,
      benzaldehyde dehydrogenase I and benzaldehyde dehydrogenase II from Acinetobacter
      calcoaceticus N.C.I.B. 8250, benzyl alcohol dehydrogenase and benzaldehyde
      dehydrogenase encoded by the TOL plasmid pWW53 in Pseudomonas putida MT53 and
      yeast K(+)-activated aldehyde dehydrogenase. Comprehensive details of the
      sequence determinations have been deposited as Supplementary Publication SUP
      50161 (5 pages) at the British Library Document Supply Centre, Boston Spa.
      Wetherby. West Yorkshire LS23 7BQ, U.K., from whom copies can be obtained on the
      terms indicated in Biochem. J. (1991) 273. 5. The extent of sequence similarity
      suggests that the benzyl alcohol dehydrogenases are related to each other and
      also to established members of the family of long-chain Zn2(+)-dependent alcohol
      dehydrogenases. Benzaldehyde dehydrogenase II from Acinetobacter appears to be
      related to the Pseudomonas TOL-plasmid-encoded benzaldehyde dehydrogenase. The
      yeast K(+)-activated aldehyde dehydrogenase has similarity of sequence with the
      mammalian liver cytoplasmic class of aldehyde dehydrogenases but not with any of
      the Acinetobacter or Pseudomonas enzymes. 2. Antisera were raised in rabbits
      against the three Acinetobacter enzymes and both of the Pseudomonas enzymes, and
      the extents of the cross-reactions were determined by immunoprecipitation assays
      with native antigens and by immunoblotting with SDS-denatured antigens. Cross
      reactions were detected between the alcohol dehydrogenases and also among the
      aldehyde dehydrogenases. This confirms the interpretation of the N-terminal
      sequence comparisons and also indicates that benzaldehyde dehydrogenase I from
      Acinetobacter may be related to the other two benzaldehyde dehydrogenases. 3. The
      amino acid compositions of the Acinetobacter and the Pseudomonas enzymes were
      determined and the numbers of amino acid residues per subunit were calculated to
      be: benzyl alcohol dehydrogenase and TOL-plasmid-encoded benzyl alcohol
      dehydrogenase, 381; benzaldehyde dehydrogenase I and benzaldehyde dehydrogenase
      II, 525; TOL-plasmid-encoded benzaldehyde dehydrogenase, 538.

PMID- 1989583
TI  - Regulation of protein turnover in skeletal and cardiac muscle.

PMID- 1989594
TI  - Galactose-dependent expression of the recombinant Ca2(+)-binding photoprotein
      aequorin in yeast.
AB  - Aequorin is a Ca2(+)-binding protein that emits light upon reacting with Ca2+ and
      has been used as a probe for monitoring changes in the intracellular free Ca2+
      concentration, [Ca2+]i. The protein consists of three components: apoaequorin
      (apoprotein), molecular oxygen and a chromophore. The present study was designed
      to conditionally express the apoaequorin cDNA of the jellyfish Aequorea victoria
      under the control of the GAL1 promoter in the yeast Saccharomyces cerevisiae and
      to investigate whether apoaequorin can be accumulated in high enough
      concentration in the cells to detect a Ca2+ signal in vitro. The results showed
      that the cells accumulated sufficient amounts of recombinant apoaequorin when
      incubated in the galactose-based medium and that the protein was active and not
      toxic to the cells, suggesting that the recombinant apoaequorin may be applicable
      to monitoring changes in [Ca2+]i in intact yeast cells.

PMID- 1989595
TI  - Isolation and identification of C-type natriuretic peptide in chicken brain.
AB  - C-type natriuretic peptide (CNP) has recently been identified in porcine brain as
      a third member of the mammalian natriuretic peptide family (1). Using a
      radioimmunoassay system for porcine CNP, we found a significant concentration of
      immunoreactive (ir-) CNP in chicken brain, from which a new peptide was isolated.
      By microsequence analysis, the amino acid sequence of the peptide was determined
      to be Gly-Leu-Ser-Arg-Ser-Cys-Phe- Gly-Val-Lys-Leu-Asp-Arg-Ile-Gly-Ser-Met-Ser
      Gly-Leu-Gly-Cys. Based on its high homology to porcine CNP, the peptide was
      designated chicken C-type natriuretic peptide. Chicken CNP also elicits
      pharmacological effects highly similar to porcine CNP, suggesting that CNP
      functions as a neuropeptide in the chicken central nervous system.

PMID- 1989596
TI  - The production by alternate splicing of two mRNAs differing by one codon could be
      an intrinsic property of neuroendocrine protein 7B2 gene expression in man.
AB  - Two types of mRNAs for neuroendocrine protein 7B2 were deduced from the sequence
      of cDNAs clones isolated from a human pituitary cDNA library. One type lacks an
      Ala100 codon present in the other. The difference is located at an intron site
      within the human 7B2 gene and can be explained by the transcriptional utilization
      of two alternate acceptor splice sites, three nucleotides apart. Heteroduplex
      analysis of DNA fragments amplified by the polymerase chain reaction indicated
      that this 7B2 mRNA dimorphism occurs in several human endocrine tissues as well
      as in other species, suggesting that the alternate processing of 7B2 gene
      transcripts may be an intrinsic mechanism of its expression and could underlie
      some yet unknown biological functions.

PMID- 1989597
TI  - 19F NMR study of the interactions of fluoride with superoxide dismutase and
      hemoglobin in erythrocytes.
AB  - F- added to an erythrocyte suspension shows two separated resonances arisen from
      intra and extracellular compartments. Cu, Zn superoxide dismutase dominates the
      longitudinal relaxation rate of the intracellular F- resonance, while diamagnetic
      interactions with hemoglobin contribute mainly to the transversal relaxation
      rate.

PMID- 1989598
TI  - Kinetics of TNF, IL-6, and IL-8 gene expression in LPS-stimulated human whole
      blood.
AB  - While the production of tumor necrosis factor (TNF) and interleukin-6 (IL-6) in
      septic shock and other inflammatory states is well established, the role of
      interleukin-8 (IL-8), a recently described neutrophil chemoattractant and
      activator, has yet to be fully elucidated. Using lipopolysaccharide (LPS)
      stimulated human whole blood as an ex vivo model of sepsis, the kinetics of
      messenger RNA (mRNA) up-regulation and protein release of these cytokines were
      examined. Two waves of cytokine gene activation were documented. TNF and IL-6
      were induced in the first wave with mRNA levels peaking between 2-4 hours and
      then rapidly declining. TNF and IL-6 protein peaked at 4-6 hours and then
      stabilized. IL-8 mRNA and protein were induced in the first wave, reached a
      plateau between 6-12 hours, and rose again in a second wave which continued to
      escalate until the end of the 24 hour study. These data demonstrate the complex
      patterns of cytokine gene expression and suggest that production of early
      mediators may augment continued expression of IL-8 to recruit and retain
      neutrophils at a site of inflammation.

PMID- 1989599
TI  - Purification and some properties of a phospholipase A2 from bovine platelets.
AB  - An intracellular form of phospholipase A2 was purified about 47,500-fold to near
      homogeneity from bovine platelets 100,000 x g supernatant by sequential use of
      column chromatographies on Heparin-Sepharose, DEAE-Sephacel, Butyl-Toyopearl,
      Sephacryl S-300, DEAE-5PW HPLC, TSK G 3000 SW HPLC and Mono Q FPLC. The final
      preparation showed a single band on SDS-polyacrylamide gel, and its molecular
      mass was estimated to be approximately 100,000 daltons. The purified PLA2 showed
      maximal activity at alkaline pH(pH 9.0-10.0) and considerable activity at 0.3-1.0
      microM calcium concentration. It hydrolyzed phosphatidylcholine containing
      arachidonate at sn-2 position with high selectivity in comparison to linoleate.

PMID- 1989600
TI  - Proteinase B is, indeed, not required for chitin synthetase 1 function in
      Saccharomyces cerevisiae.
AB  - Previous genetic evidence led to the conclusion that proteinase B of yeast was
      not involved in the function of chitin synthetase 1 (Chs1), based on the
      demonstration of normal septum formation, cell division and chitin deposition in
      mutants devoid of the proteinase (Zubenko, G.S., Mitchell, A.P., and Jones, E.W.
      (1979) Proc. Natl. Acad. Sci. USA 76, 2395-2399). Later, however, it was found
      that the essential enzyme for septum formation is chitin synthetase 2, whereas
      Chs1 acts as an auxiliary enzyme, whose absence results in daughter cell lysis
      under acidic conditions (Cabib, E., Sburlati, A., Bowers, B. and Silverman, S.J.
      (1989) J. Cell Biol. 108, 1665-1672). By using the lytic behavior as a criterion,
      we have now found that prb1 strains are not defective in Chs1 function. Certain
      strains contain a recessive suppressor of lysis which could mask the Chs1 defect.
      However, appropriate crosses and transformation experiments showed that the prb1
      mutants do not harbor the suppressor. It may now be concluded with confidence
      that proteinase B is not required for chitin synthetase 1 function.

PMID- 1989601
TI  - Oxygen radical production during ischemia-reperfusion in the isolated perfused
      rat liver as monitored by luminol enhanced chemiluminescence.
AB  - We have applied the Luminol enhanced chemiluminescence technique to the isolated
      perfused rat liver during ischemia and reperfusion to monitor the production of
      oxygen radicals in tissue. Livers under perfusion with Luminol-containing buffer
      were subjected to 30 minutes of global ischemia followed by 60 minutes of
      reperfusion. Their chemiluminescence was continuously monitored to obtain the
      time course of oxygen radical production. Transient bursts of oxygen radical
      production were observed in the livers as indicated by chemiluminescence changes
      on reperfusion. Superoxide dismutase treatment abolished while catalase treatment
      enhanced the reperfusion-induced chemiluminescence transient.

PMID- 1989602
TI  - Genomic organization of the alpha chain of the human C4b-binding protein gene.
AB  - C4b-binding protein (C4bp) is a serum glycoprotein that is one of the regulators
      of the complement activation (RCA) family. This protein is composed of
      structurally related 70-kDa (alpha chain) and 45-kDa (beta chain) polypeptides.
      The alpha chain of C4bp (C4bp alpha) consists of eight short consensus repeats
      (SCR), which constitute the amino-terminal 491 residues. Human C4bp is also one
      of the acute-phase reactants. In order to clarify the genetic basis of the SCR
      and to understand the regulatory mechanisms of C4bp synthesis, we isolated 6
      genomic DNA clones covering all of the human C4bp alpha gene. This gene consists
      of 12 exons and spans about 40 kb. Each of the SCRs is encoded by a single exon,
      except for the second SCR (SCR II), which is encoded by two separate exons,
      demonstrating that human C4bp alpha has a split SCR at the genomic level. The 5'
      flanking region was sequenced up to 380 bases upstream from the putative
      transcription initiation site. Several possible binding sites for transcription
      factors were identified.

PMID- 1989603
TI  - Molecular insight into the asymmetric distribution of pathogenetic human
      mitochondrial DNA deletions.
AB  - Pathogenetic human mitochondrial DNA deletions occur very rarely in the minor
      region between the origins of replication. In order to understand the molecular
      basis of this asymmetry, we analyzed the structure of such a 4.680 kilobase
      deletion (position 471 - 5151). Directly repeated sequences (12/13 nucleotides)
      are present in the deletion junction, both promoters of heavy chain replication
      and both ribosomal RNA genes are deleted, and the 5' extent further narrows the
      absolute limits of mitochondrial DNA deletions. Several factors are identified
      that may contribute to the paucity of minor region deletions.

PMID- 1989604
TI  - Recombinant human interleukin-1 inhibits plasminogen activator inhibitor-1 (PAI
      1) production by human articular cartilage and chondrocytes.
AB  - Human articular cartilage and chondrocyte monolayers in culture constitutively
      produced plasminogen activator inhibitor-1 (PAI-1) protein and mRNA, as assessed
      by a specific enzyme-linked immunosorbent assay and Northern blotting analysis,
      respectively. Recombinant human interleukin-1 (IL-1) invoked a dose-dependent
      inhibition of PAI-1 production in both cartilage and chondrocyte cultures. The
      inhibitory effect of IL-1 was observed between 2-8h after addition of the
      cytokine, while the optimal dose was between 10-100U/ml IL-1 alpha (57-570pM IL-1
      alpha). Results obtained by Northern analysis of chondrocyte total RNA reflected
      those found for the PAI-1 antigen, namely, that nontreated chondrocytes showed
      PAI-1 mRNA which was reduced by IL-1 treatment. To our knowledge, this is the
      first report where IL-1 has been found to inhibit PAI-1 expression. Since IL-1
      has been shown before to cause human cartilage destruction and a correlated
      change in plasminogen activator activity, it could be that a concomitant
      reduction in PAI-1 levels by IL-1 may be significant in the control of these
      changes in cartilage.

PMID- 1989605
TI  - Interleukin-1 beta, tumor necrosis factor and forskolin stimulate the synthesis
      and secretion of group II phospholipase A2 in rat mesangial cells.
AB  - Treatment of rat glomerular mesangial cells with interleukin-1 beta, tumor
      necrosis factor or forskolin resulted in the release of phospholipase A2 activity
      in the culture medium. Essentially all of this phospholipase A2 activity was
      bound to immobilized monoclonal antibodies raised against rat liver mitochondrial
      14 kDa group II phospholipase A2. Gelfiltration confirmed the absence of higher
      molecular weight phospholipases A2 in the culture medium. Immunoblot experiments
      showed the virtual absence of this 14 kDa group II phospholipase A2 in
      unstimulated mesangial cells. The time-dependent increase of phospholipase A2
      activity in both cells and culture medium upon stimulation with interleukin-1
      beta plus forskolin is accompanied with elevated 14 kDa phospholipase A2 protein
      levels. These results indicate that the increased phospholipase A2 activity upon
      treatment of mesangial cells with these stimulators is due to increased synthesis
      of group II phospholipase A2. Over 85% of this newly synthesized phospholipase A2
      appears to be secreted from the cells.

PMID- 1989606
TI  - Effects of estrogens on MCF-7 cells: positive or negative regulation by the
      nature of the ligand-receptor complex.
AB  - The present study demonstrates that the nature of the binding of estrogens to the
      hormone-binding domain of the estrogen receptor (ER) modifies the responses of
      estrogen-dependent cells. We report here that 10 nM estradiol (E2) forms
      noncovalent associations with the ER, increases the level of ER and Progesterone
      Receptors (PR) in ER+ MCF-7 human breast cancer cells in culture following short
      term or long-term exposure to E2. In contrast, 10 nM 16-alpha-hydroxyestrone (16
      alpha-OHE1), a physiological metabolite of E2, in short-term cultures is
      equivalent to E2, but upon long-term incubation, 16 alpha-OHE1 forms covalent
      associations with the ER, produces a marked decrease in ER and PR levels reaching
      values similar to, or below to that of control cells.

PMID- 1989607
TI  - The leader sequence of streptokinase is responsible for its post-translational
      carboxyl-terminal cleavage.
AB  - When the expression of streptokinase from two tac promoter-controlled expression
      vectors, one of these deleted a putative leader sequence of streptokinase and the
      other not, was compared, both normal and degraded streptokinase were detected in
      proteins expressed from the leader-contained vector, but only normal
      streptokinase was detected from the leader-deleted vector. These findings
      indicate that the characteristic carboxyl-terminal cleavage of streptokinase is
      correlated with its leader sequence and occurs during the defective secretion.
      The homogeneous preparation of streptokinase was facilitated by expressing from
      this leader-deleted vector.

PMID- 1989608
TI  - Growth inhibition of human keratinocytes by antisense c-myc oligomer is not
      coupled to induction of differentiation.
AB  - To study the relationship between cell growth and differentiation in human
      keratinocytes, we examined the effect of the antisense oligomer of c-myc mRNA.
      This oligomer is stable in culture medium. A 24 h incubation of cells with 5
      microM antisense c-myc oligomer resulted in a 48.2% decrease in c-myc protein and
      inhibited cell growth by 80.7% compared to the sense c-myc oligomer. In contrast,
      antisense c-myc oligomer had no effect on differentiation when the population of
      involucrin-positive cells and cornified envelope formation were used as
      differentiation markers. These results show that antisense c-myc oligomer
      inhibits cell growth but does not induce differentiation in normal human
      keratinocytes. Therefore, cell growth and differentiation are not necessarily
      coupled in these cells.

PMID- 1989609
TI  - Demonstration of heat production associated with spreading depression in the
      amphibian retina.
AB  - Using thin film of synthetic pyroelectric material, polyvinylidene fluoride,
      sensitive heat-sensors were constructed for the purpose of detecting heat
      production associated with the phenomenon of spreading depression in isolated
      amphibian retinae. Measurements with these sensors revealed the existence of
      large heat production, which closely follows the electrical sign of spreading
      depression. Studies of the effects of chemical agents known to affect spreading
      depression have demonstrated the usefulness of heat measurements.

PMID- 1989610
TI  - Inhibitory effect of porphyrins on the proliferation of mouse spleen lymphocytes
      in vitro.
AB  - The influence of various porphyrins (deuteroporphyrin IX, mesoporphyrin IX,
      protoporphyrin IX, hematoporphyrin) and two related compounds (hemin, biliverdin)
      on the spontaneous proliferation of mouse spleen lymphocytes has been estimated
      in vitro by the 3H-thymidine uptake assay. It has been found that porphyrins
      (endogenous ligands for the mitochondrial benzodiazepine receptor) produce a
      concentration-dependent inhibition of 3H-thymidine incorporation into the DNA of
      these cells. Metalloporphyrin-hemin has been observed to evoke a weak inhibitory
      effect, in a high concentration (10(-4)M), whereas biliverdin, a porphyrins
      degradation product, was inactive in the same experimental conditions. Those
      findings indicate that endogenous porphyrins, presumably acting through the
      mitochondrial benzodiazepine receptor, could regulate the proliferation of mouse
      spleen lymphocytes in vitro.

PMID- 1989611
TI  - Purification of monomeric agmatine iminohydrolase from soybean.
AB  - Agmatine iminohydrolase (EC 3.5.3.12) was purified to homogeneity from the
      cytosol of soybean (Glycine max) axes by chromatographic separations on Sephadex
      G-25, Bio-rex 70, and agmatine-affinity columns. The enzyme was homogeneous by
      the criteria of analytical gel electrophoresis. Molecular weights estimated by
      Sephadex G-100 gel and sodium dodecyl sulfate polyacrylamide gel electrophoresis
      were 70,000, indicating that the soybean axes enzyme is a monomer, in contrast to
      the dimeric enzymes from corn and rice. The isoelectric point determined by gel
      electrofocusing was 7.5, higher than that of the corn enzyme (4.7). The optimal
      pH and temperature for activity were 6.5 and 50 degrees C, respectively. The
      enzyme has high specificity for agmatine, and the Km for agmatine was 2.5 x 10(
      3) molar. The enzyme was sensitive to Cu2+ and also was inhibited by p
      hydroxymercuribenzoate.

PMID- 1989612
TI  - Demonstration of extrinsic DNA from immune complexes in plasma of a patient with
      systemic lupus erythematosus.
AB  - Antigen DNA isolated from immune complexes present in plasma of three patients
      with active systemic lupus erythematosus using an affinity column was cloned and
      sequenced. One clone, designated pKS7, was found to have a region homologous with
      that of the E. coli metK gene, and another, designated pKS8, had a region
      homologous with a sequence including the replication origin of bacteriophage f1.
      Gel retardation assay revealed that pKS7 and pKS8 interacted with the patient's
      IgG fraction to form immune complexes, respectively. The affinity-purified
      antigen DNA was proved to be originated from bacteria or bacteriophage.

PMID- 1989614
TI  - Solubilization of prostaglandin D2 binding protein from porcine temporal cortex.
AB  - Prostaglandin (PG) D2 binding activity was retained at the highest level in the
      P2 fraction prepared from porcine temporal cortex with the use of buffer
      containing mannitol and quinacrine. Then, the activity in this fraction was
      solubilized with maximal recovery by 10 mM CHAPS. The specific PGD2 binding time
      dependently increased and was saturated at around 70 nM. Scatchard plots were
      fitted to a straight line with a Kd value of 20 nM and Bmax of 120 fmol/mg
      protein. The binding sites showed high specificity for PGD2. In addition, heat
      and trypsin treatments remarkably decreased the binding activity. These results
      suggest that the specific binding protein for PGD2 can be solubilized from these
      membranes.

PMID- 1989613
TI  - P460 of hydroxylamine oxidoreductase of Nitrosomonas europaea: Soret resonance
      Raman evidence for a novel heme-like structure.
AB  - P460, an iron-containing chromophore at the active site of Hydroxylamine
      Oxidoreductase of the ammonia-oxidizing bacterium Nitrosomonas europaea, is a
      macrocycle of unknown structure with a Soret-like 460-nm absorption band in the
      ferrous form. The pigment can also be isolated in a peptide, "P460-Fragment".
      Resonance Raman spectroscopy (lambda ex = 457.9 nm) suggests that P460 is a new
      type of heme with symmetry properties lower than those of protophorphyrin IX or
      chlorins and similar to those of chlorophylls and isobacteriochlorins. Some of
      the resonance Raman vibrations of P460 are shifted in HAO as compared to those of
      P460-Fragment.

PMID- 1989615
TI  - Hormone controlled phosphorylation and degradation of CYP2B1 and CYP2E1 in
      isolated rat hepatocytes.
AB  - Addition of adrenalin to primary rat hepatocytes caused a 3- and 2-fold increase
      in [32P]-incorporation into CYP2E1 and CYP2B1, respectively. Adrenalin also
      increased the rate of CYP2E1 degradation at similar concentrations as needed for
      phosphorylation of the protein (r = 0.93), but did not influence the degradation
      rate of CYP2B1. Ethanol (75 mM) completely protected from adrenalin dependent
      phosphorylation and degradation of CYP2E1, but did not influence CYP2B1 on these
      parameters. Examination of para-nitrophenol hydroxylase revealed that ethanol
      stabilized the catalytically active form of CYP2E1. Insulin treatment caused a
      stabilization of CYP2E1, but did not affect CYP2B1 degradation. It is concluded
      that degradation of CYP2E1 is the subject of hormonal control, whereas CYP2B1
      decomposition is accomplished in a different and a less regulated manner.

PMID- 1989616
TI  - Regional expression of the nerve growth factor gene family in rat brain during
      development.
AB  - The developmental expression patterns of three members (NGF, NGF-2/NT-3, and
      BDNF) of the NGF family in rat brain are different. NGF-2/NT-3 mRNA was the first
      detected during development followed by NGF and BDNF mRNAs. A substantial amount
      of NGF mRNA was found to be synthesized in the hippocampus and the cortex, and
      this regional expression pattern did not change during development. In contrast,
      NGF-2/NT-3 mRNA was detected in almost all the brain regions examined in the
      early developmental stage. In the late stage, the transcript was found in high
      concentration only in the hippocampus and the cerebellum. BDNF mRNA was widely
      distributed, and its level was augmented in the late developmental stage.

PMID- 1989618
TI  - Biodegradation of triiodophenol by cell-free extracts of a pentachlorophenol
      degrading Flavobacterium sp.
AB  - Pentachlorophenol (PCP) degrading Flavobacterium sp. ATCC 39723 was found to
      degrade other polyhalogenated phenolic compounds, including triiodophenol,
      tribromophenol, and trichlorophenol. Each compound was able to induce the
      degradation of the other compounds. A PCP Flavobacterium sp. mutant, F-2, was
      unable to degrade any of the halogenated compounds. The results suggest that all
      of the polyhalogenated phenols were degraded by the same enzyme system. This
      observation led us to exploit the sensitive leuco crystal violet assay, which
      measures the iodide released from triiodophenol. Cell free extracts from PCP
      induced cells were able to release iodide from triiodophenol. The reaction
      required NADPH and oxygen.

PMID- 1989617
TI  - Quinone mediated electron transport system in the filarial parasite Setaria
      digitata.
AB  - Setaria digitata, a cattle filarial parasite, is known to have peculiarities such
      as hydrogen peroxide (H2O2) production, cyanide insensitivity, absence of
      cytochromes and presence of quinones. Estimation of mitochondrial H2O2 with
      different substrates and inhibitors showed that salicylhydroxamic acid (SHAM),
      the alternative oxidase inhibitor, inhibited the H2O2 production maximally. Based
      on the inhibitory studies with rotenone, antimycin A, o-hydroxydiphenyl, SHAM and
      2 thenoyltrifluoroacetone, a mechanism for the electron transport is proposed.
      Quinone Q8 seems to have a central role, hence inhibitors at the level of
      quinones might prove to be effective in designing drugs for filariasis.

PMID- 1989619
TI  - Basic fibroblast growth factor is a substrate for phosphorylation by human
      neutrophil ecto-protein kinase activity.

PMID- 1989620
TI  - Elafin is a potent inhibitor of proteinase 3.
AB  - Elafin, a human skin derived inhibitor of human leukocyte elastase, was tested
      for inhibitory activity against proteinase 3, an elastin degrading proteinase of
      neutrophils. The inhibitory activity of elafin was compared with
      antileukoprotease and eglin C. Elafin proved to be a potent inhibitor of elastin
      FITC degradation showing an IC 50 of 9.5 x 10(-9) M. Potency was found to be more
      than 100-fold higher as compared with antileukoprotease and eglin C.

PMID- 1989622
TI  - Inhibitory effect of okadaic acid on carbachol-evoked secretion of catecholamines
      in cultured bovine adrenal medullary cells.
AB  - We examined the effect of okadaic acid on catecholamine secretion caused by
      carbachol in cultured bovine adrenal medullary cells. Treatment of cells with 100
      nM okadaic acid for 3-24 hr produced an inhibition of catecholamine secretion
      stimulated by carbachol. The half-maximal and maximal inhibition of secretion was
      observed at 40 nM and 300 nM okadaic acid for 24 hr, respectively. Okadaic acid
      also inhibited veratridine- and high K(+)-induced secretion but not ionomycin
      induced secretion. Okadaic acid strongly suppressed 45Ca2+ influx and slightly
      inhibited 22Na+ influx in carbachol-stimulated cells. These results suggest that
      okadaic acid inhibits carbachol-evoked secretion of catecholamines mainly by
      suppression of Ca2+ influx in adrenal medullary cells.

PMID- 1989621
TI  - Isolation and partial characterization of a cystine-rich basic heparin-binding
      protein from bovine platelets.
AB  - We report the isolation and partial characterization of a so far unidentified
      basic platelet protein. Delipidated bovine platelets were extracted at pH 2.1.
      The extract was subjected to differential precipitation at pH 5.4-5.5 and by
      ammonium sulfate, then it was further purified by ion exchange chromatography on
      DEAE and CM cellulose columns in an urea containing medium. The major protein
      peak eluted from the CM cellulose column by NaCl gradient contained a protein in
      electrophoretically homogeneous form. It consists of a single polypeptide chain
      with an Mr of 28,000 as estimated by SDS PAGE. It was shown to be extremely rich
      in lysine and cystine and possessed a highly basic character (pI 9.8-10.1). On
      this basis the term cystine-rich basic protein (CRBP) was proposed for the new
      protein. Unlike some other low Mr basic proteins it did not bind calmodulin and
      troponin C, however, it showed significant heparin neutralizing activity.

PMID- 1989623
TI  - Isolation and partial characterization of the formyl peptide receptor components
      on human neutrophils.
AB  - The receptor for formylated peptides such as FMLP has been reported to consist of
      glycoprotein components ranging from 24-95 kDa, and to exhibit both high and low
      affinity for ligand. Controversy exists on the molecular size and number of these
      components, and whether the different affinities represent distinct ligand
      binding sites. In this study, the receptor was found to be comprised of
      components, of 94, 68, and approximately 40 kDa molecular size. Competitive
      binding inhibition experiments showed that FMLP bound to the components in the
      following order from highest to lowest affinity: 68 kDa greater than
      approximately 40 kDa greater than 94 kDa. Our findings suggest that the FMLP
      receptor of human neutrophils contains at least three components, and that each
      component has a different affinity for FMLP.

PMID- 1989624
TI  - Bone morphogenetic protein-2 stimulates alkaline phosphatase activity and
      collagen synthesis in cultured osteoblastic cells, MC3T3-E1.
AB  - The activities of three bone morphogenetic proteins (BMPs), BMP-1, BMP-2 and BMP
      3, on alkaline phosphatase activity, collagen synthesis and DNA synthesis were
      studied in cultured osteoblastic cells, MC3T3-E1. Treatment of cells with BMP-2
      for 48 h induces an increase in cellular alkaline phosphatase activity. This
      stimulatory effect is evident at a concentration as low as 20 ng/ml of BMP-2 and
      becomes greater with increasing doses of BMP-2. The BMP-2-induced increase in
      alkaline phosphatase activity is enhanced by the presence of beta-estradiol,
      dexamethasone or 1 alpha, 25(OH)2D3. BMP-2 and BMP-3 slightly but significantly
      stimulate collagen synthesis. None of the BMPs stimulates DNA synthesis in MC3T3
      E1 cells at doses tested. These results indicate that BMPs act directly on
      osteoblastic cells and stimulate the expression of the osteoblastic phenotypes.

PMID- 1989625
TI  - Inhibition of the metabolism of phosphatidylethanol and phosphatidic acid, and
      stimulation of insulin release, by propranolol in intact pancreatic islets.

PMID- 1989626
TI  - New directions in monoamine oxidase A and B selective inhibitors and substrates.
AB  - Identification, cellular localization, and cDNA cloning of MAO subtypes A and B
      have increased the insight into the pharmacology of these enzymes, whose primary
      functions are intra- and extraneuronal inactivation of neurotransmitter
      (dopamine, noradrenaline and serotonin) and other biogenic amines. In addition,
      MAO oxidizes the inert uncharacteristic tertiary amine, MPTP, to the parkinson
      inducing dopaminergic neurotoxin, MPP+, and the novel secondary amine
      anticonvulsant milacemide to the inhibitory amino acid neurotransmitter, glycine.
      These recent developments have provided new therapeutic perspectives for the
      management of Parkinson's disease and seizure disorders via the use of selective
      inhibitors and amino acid amine prodrug substrates of MAO-B.

PMID- 1989627
TI  - Intracellular mechanisms in exocytotic secretion.

PMID- 1989628
TI  - Xenobiotic-metabolizing enzymes in human respiratory nasal mucosa.
AB  - Study of oxidative and non-oxidative xenobiotic-metabolizing enzymes was
      undertaken in microsomal and cytosolic fractions of two human livers, 10
      individual and several pooled samples of human respiratory nasal mucosa obtained
      by surgical operation of male and female patients affected by hypertrophy of the
      inferior turbinates. The purity of nasal microsomes was checked by electron
      microscopy and marker enzyme assay. The pooled samples of respiratory nasal
      epithelium contained, relative to liver, a low amount of cytochrome P450 (about
      25 pmol/mg protein) and associated biotransformation activities, and a low level
      of other components of the mixed-function oxidase system such as cytochrome b5,
      NADH and NADPH-cytochrome c reductase however the NADH-cytochrome b5 reductase
      activity was comparable to that of liver. The P450-dependent monooxygenase
      activities such as ethoxycoumarin O-deethylase, ethoxyresorufin O-deethylase and
      the dimethylnitrosamine N-demethylase were found in nearly all nasal microsomal
      specimens. The aniline hydroxylase and the aminopyrine or hexamethylphosphoramide
      N-demethylases were detected only in the pooled nasal samples. With regard to the
      non-oxidative enzymes, the activities of glutathione S-transferase, DT
      diaphorase, epoxide hydrolase, UDP-glucuronyl-transferase, carbonyl reductase,
      benzaldehyde and propionaldehyde dehydrogenases, were investigated both in the
      individual and pooled nasal tissues and livers. These activities were similar in
      nasal and liver tissue, except for UDP-glucuronyltransferase which was not
      detected in nasal mucosa. The present findings demonstrate that the respiratory
      section of human nose contains a wide array of oxidative and non-oxidative
      enzymes, which could play a crucial role in the bioactivation or detoxication in
      situ of inhaled xenobiotics.

PMID- 1989629
TI  - 2,4-Dihydroxybenzylamine: a specific inhibitor of glutathione reductase.
AB  - The high intracellular level of glutathione is maintained, in part, by the
      important redox enzyme glutathione reductase. This report describes the
      properties of a new inhibitor of glutathione reductase, 2,4-dihydroxybenzylamine
      (2,4-DHBA). The inhibition of glutathione reductase by both 2,4-DHBA and 1,3
      bischloroethyl-nitrosourea (BCNU) requires the presence of the co-factor NADPH.
      However, the inhibition caused by 2,4-DHBA was found to occur much more rapidly.
      Inhibition of glutathione reductase was time dependent, involved a stoichiometric
      titration of the enzyme, and was not reversed by gel-filtration indicating an
      irreversible inhibitory mechanism. The drug interacted at two inhibitory sites as
      determined by a Hill-type plot analysis. 2,4-DHBA was shown to compete with the
      substrate oxidized glutathione, and the reducing agents, glutathione and
      dithioerythritol, were found to protect the enzyme from its inhibitory effect.
      These results suggest that the inhibition may entail a free radical effect at or
      near the active site. A structure-activity analysis with other meta
      dihydroxybenzene derivatives revealed that the inhibition of glutathione
      reductase was unique to 2,4-dihydroxybenzylamine.

PMID- 1989630
TI  - Elevation of rat pulmonary, hepatic and lung surfactant lipids by fly ash
      inhalation.
AB  - Fly ash contains many polycyclic aromatic hydrocarbons and genotoxic trace
      elements. In rats, fly ash exposure profoundly affects lung and liver histology.
      In the present study, the effect of fly ash inhalation on lung and liver lipids
      of rats was examined. Male Wistar strain rats were exposed daily to fly ash (0.27
      +/- 0.01 mg/L air) in an inhalation chamber, 6 hr daily over a period of 15 days,
      and were killed on various days, i.e. 16, 30, 60, and 120. Fly ash inhalation
      significantly (P less than 0.05) increased total phospholipids (PL),
      phosphatidylcholine (PC) and phosphatidylethanolamine (PE) in lungs. PC and
      dipalmitoylphosphatidylcholine (DPPC) contents in microsomes and lung surfactant
      also were significantly (P less than 0.05) higher in rats exposed to fly ash
      compared to control group animals. Radiolabeled precursor incorporation studies
      indicated that fly ash induced the synthesis of PC and DPPC by both CDP-choline
      pathway and N-methylation of PE in lung microsomes and enhanced their secretion
      into lung surfactant. In liver, PC and PE contents were elevated significantly (P
      less than 0.05) by fly ash exposure on days 16 and 30 respectively. A similar
      elevation of PC was observed in hepatic microsomes; this increase was due to its
      increased synthesis. However, the increased synthesis of PC in liver occurred to
      a greater extent by the N-methylation pathway than by the CDP-choline pathway.

PMID- 1989631
TI  - Inhibition of tryptophan hydroxylase by food-derived carcinogenic heterocyclic
      amines, 3-amino-1-methyl-5H-pyrido[4,3-b]indole and 3-amino-1,4-dimethyl-5H
      pyrido[4,3-b]indole.
AB  - Food-derived and carcinogenic heterocyclic amines, 3-amino-1-methyl-5H-pyrido[4,3
      b]indole (Trp-P-2) and 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1),
      were found to inhibit the activity of tryptophan hydroxylase (TPH) prepared from
      serotonin-producing murine mastocytomas, P-815 cells. Inhibition of TPH by Trp-P
      2 was found to be competitive with the substrate L-tryptophan and non-competitive
      with the cofactor (6R)-L-erythro-5,6,7, 8-tetrahydrobiopterin. The inhibition
      proved to be reversible; by dialyzing the sample incubated with Trp-P-2, the
      enzyme activity could be fully recovered. Among a series of heterocyclic amines
      examined, Trp-P-1, Trp-P-2 and some other heterocyclic amines inhibited TPH
      activity. Trp-P-2 and other heterocyclic amines were the newly discovered
      naturally occurring inhibitors of the indoleamine metabolism.

PMID- 1989633
TI  - Quantitative relationship of lysosomal glycogen accumulation to lysosomal alpha
      glucosidase inhibition in castanospermine-treated rats.
AB  - To quantitatively examine the relationship between lysosomal acid alpha
      glucosidase (LAAG, alpha-D-glucoside glucohydrolase, EC 3.2.1.20) inhibition and
      glycogen accumulation, rats were treated with castanospermine (CS), and liver
      lysosomal/mitochondrial fractions were analyzed for glycogen content and LAAG
      activity. Liver lysosomal glycogen accumulation positively correlated (r = 0.90)
      with the amount of LAAG inhibition when inhibition was about 50% or greater.
      Glycogen did not accumulate when LAAG inhibition was less than 50%. The route of
      CS administration had little effect on the amount of LAAG inhibition observed. In
      rats killed 17 hr after CS administration, the doses estimated to cause 50% LAAG
      inhibition were 0.77, 0.11, and 0.22 mg/kg for i.p., i.v., and oral
      administration respectively. After 89% inhibition of LAAG activity with a single
      oral dose of 10 mg CS/kg, LAAG activity returned to 50% of normal value in about
      2.5 days. Accumulated glycogen disappeared as LAAG activity recovered.
      Surprisingly, twelve daily CS doses of 1 mg/kg had only a small cumulative effect
      on LAAG inhibition and did not cause more glycogen accumulation than a single
      dose.

PMID- 1989632
TI  - Putrescine or spermidine binding site of aminopropyltransferases and competitive
      inhibitors.
AB  - A model of the active site of aminopropyltransferases was proposed based on the
      study of a number of monoamino and diamino compounds as potential inhibitors and
      substrates, respectively, of spermidine synthase purified from pig liver. The
      active site seems to have a relatively large hydrophobic cavity adjacent to a
      negatively charged site, to which a protonated amino group of putrescine binds,
      with another amino group of putrescine being situated in the hydrophobic cavity
      as a free form to be aminopropylated by decarboxylated S-adenosylmethionine. On
      the basis of the above-mentioned model, another modified one was proposed for
      spermine synthase, and several compounds mentioned model, another modified one
      was proposed for spermine synthase, and several compounds designed according to
      the modified model were found to potently inhibit spermine synthase, purified
      from rat brain, in competition with spermidine. The newly developed inhibitors
      were about two orders of magnitude more potent in vitro than a known inhibitor of
      spermine synthase, dimethyl(5'-adenosyl)sulfonium perchlorate.

PMID- 1989635
TI  - Interspecies variability in mitoxantrone metabolism using primary cultures of
      hepatocytes isolated from rat, rabbit and humans.
AB  - Metabolism of mitoxantrone was studied in primary cultures of hepatocytes freshly
      obtained from rat, rabbit and humans. Metabolic pattern was evaluated by a high
      performance liquid chromatographic method which specifically resolved
      mitoxantrone from its mono- and dicarboxylic acid derivatives. Studies were
      carried out over 48 hr and at [14C]mitoxantrone concentrations ranging between 1
      and 20 microM. In all species studied, metabolism occurred: extracellular
      unchanged mitoxantrone concentrations represented around 50, 25 and 20% of total
      extracellular radiolabel at 48 hr in rat, rabbit and humans, respectively.
      Although minor interspecies variability was observed in total amount of drug
      biotransformed by hepatocytes, large variability in the metabolic pattern
      occurred between the different species: hence, in rats the main derivatives were
      two polar compounds and only trace amounts of the mono- and dicarboxylic acid
      metabolites were present. In both rabbits and humans however, these polar
      derivatives represented minor metabolic pathways and the main metabolites were
      the mono- and dicarboxylic acid derivatives. While the percentage of total
      biotransformation was similar in these two latter species, the monocarboxylic
      acid derivative was the main metabolite in rabbits while the dicarboxylic acid
      was predominant in humans. Only small interindividual differences (N = 4) were
      observed in the metabolism of mitoxantrone by human hepatocytes in primary
      culture. These data demonstrated that: (i) in all species, mitoxantrone was
      biotransformed into metabolites which rapidly effluxed in the extracellular
      compartment, (ii) there were low interspecies differences between rat, rabbit and
      humans in terms of total biotransformed drug, but (iii) large interspecies
      variability was demonstrated in the qualitative (rat versus both rabbit and
      human) and relative (rabbit versus man) patterns of the metabolites. Furthermore,
      the metabolism of mitoxantrone was linear over a wide range of concentrations
      (i.e. 1-20 microM). In conclusion, rabbit appears to be the animal species most
      closely related to humans in terms of mitoxantrone metabolism.

PMID- 1989634
TI  - In vivo and in vitro effects of helenalin on mouse hepatic microsomal cytochrome
      P450.
AB  - Helenalin, a natural plant product with significant antitumor activities,
      decreased male BDF1 mouse hepatic microsomal cytochrome P450 contents in vivo and
      in vitro. A single i.p. dose of 25 mg helenalin/kg body weight significantly (P
      less than 0.05) decreased microsomal cytochrome P450 contents and inhibited
      cytochrome P450-dependent mixed-function oxidase activities within 1-2 hr post
      exposure. Helenalin (1.0 mM) decreased microsomal cytochrome P450 contents in
      vitro by 11% in the absence of NADPH and by 32% in the presence of NADPH. These
      in vitro and in vivo decreases in cytochrome P450 were accompanied by comparable
      decreases in total microsomal heme contents. Helenalin (1.0 mM) increased mouse
      hepatic microsomal oxygen consumption and NADPH utilization by 3.2 and 5.4
      nmol/min/mg protein respectively. Helenalin (1.0 mM) significantly (P less than
      0.05) increased microsomal lipid peroxidation in vitro, and this helenalin
      induced increase in lipid peroxidation was inhibited completely by the addition
      of 0.05 mM EDTA. However, microsomal cytochrome P450 contents were equally
      affected by helenalin in the presence or absence of EDTA, suggesting that lipid
      peroxidation did not contribute to the helenalin-induced decrease in cytochrome
      P450. The addition of 0.05 mM hemin to microsomes treated in vitro with 1.0 mM
      helenalin resulted in a 58% recovery of cytochrome P450 contents. This ability of
      hemin to reconstitute cytochrome P450 in helenalin-treated microsomes suggests
      that helenalin produced a selective loss of heme from the cytochrome P450
      holoprotein, and that the resulting cytochrome P450 apoprotein remained intact
      after helenalin treatment. The increased loss of microsomal cytochrome P450
      produced by helenalin in the presence of NADPH suggests that a helenalin
      metabolite may be responsible for heme loss and the in vitro destruction of
      cytochrome P450.

PMID- 1989636
TI  - Ganciclovir permeation of the human erythrocyte membrane.
AB  - The membrane permeation of ganciclovir (DHPG)--a structural analogue of acyclovir
      (ACV) with activity against cytomegalovirus--was investigated in human
      erythrocytes at 37 degrees with an "inhibitor-stop" assay. DHPG influx was
      nonconcentrative, occurred without permeant metabolism, and was rate-saturable.
      While substantial inhibition of the influx of 13 microM DHPG occurred only in the
      presence of permeants of the purine nucleobase carrier, nucleosides and
      inhibitors of nucleoside transport markedly inhibited DHPG influx at higher DHPG
      concentrations (greater than or equal to 200 microM). Adenine and dilazep (a
      potent inhibitor of the nucleoside carrier) each inhibited the influx of DHPG
      only partially; when present together, however, they inhibited DHPG permeation
      completely. DHPG permeation via the purine nucleobase carrier (Km = 0.89 mM) was
      characterized by assessing influx in the presence of 1.0 microM dilazep. Adenine
      and ACV were shown to competitively inhibit this process, while DHPG (Ki = 0.90
      mM) was found to competitively inhibit adenine influx. DHPG influx via the
      nucleoside carrier (Km = 14 mM) was characterized by assessing influx in the
      presence of 2 mM adenine. DHPG (Ki = 10 mM) also appeared to competitively
      inhibit the influx of 5-iodo-2'-deoxyuridine. These results indicate that DHPG
      permeates the human erythrocyte membrane primarily by the purine nucleobase
      carrier and secondarily by the nucleoside transporter.

PMID- 1989637
TI  - Determination of thiazole-4-carboxamide adenine dinucleotide (TAD) levels in
      mononuclear cells of leukemic patients treated with tiazofurin.
AB  - Tiazofurin is an oncolytic agent which has shown therapeutic activity in end
      stage acute nonlymphocytic leukemia (ANLL) and blast crisis of chronic
      granulocytic leukemia (CGL-BC). Tiazofurin is anabolized to the active
      metabolite, thiazole-4-carboxamide adenine dinucleotide (TAD), which inhibits IMP
      dehydrogenase activity, leading to reduction of guanylate pools and cessation of
      cancer cell proliferation. The concentration of TAD in neoplastic cells of
      patients treated with tiazofurin should be a good indicator of sensitivity to the
      drug and also might herald the emergence of drug-resistant cells. Therefore, the
      precise quantitation of TAD in cancer cells during tiazofurin treatment is
      essential. In this paper we report a highly sensitive method for the
      determination of TAD in biological samples. With this technique, in addition to
      TAD, thirteen other biologically relevant adenine, guanine, cytosine and uridine
      nucleotides can be separated and quantitated accurately. TAD standard was
      separated on a Waters Partisil 10-SAX column in a RCM-10 module using an ammonium
      phosphate buffer system. TAD eluted at 21 min with a limit of detection of 15
      pmol and linearity up to 3 nmol. The coefficient of variation was 0.6 +/- 0.1%
      for retention time and 2 +/- 0.3% for TAD concentration. Recovery of TAD was 96%
      with reproducibility of 98%. To examine the applicability of this method to a
      clinical setting, blood samples were obtained from a patient with CGL-BC and
      leukocytes were separated on a Ficoll-Hypaq gradient, extracted with
      trichloroacetic acid, and an aliquot was analyzed on HPLC. The TAD peak was
      identified by comparing the retention time and spectral analysis of the standard.
      After the patient was treated with a 2200 mg/m2 (12.7 mM) dose of tiazofurin, the
      TAD concentrations in the mononuclear cells at 2, 6, and 24 hr were 23.1, 13.6,
      and 0.8 microM. TAD levels at 2, 6, and 24 hr after a tiazofurin dose of 3300
      mg/m2 (21.1 mM) were 42.8, 26.1, and 1.4 microM respectively.

PMID- 1989638
TI  - 3'-Azido-3'-deoxythymidine inhibition of human lymphocyte cytolytic function in
      vitro.
AB  - Despite administration of 3'-azido-3'-deoxythymidine (AZT, Zidovudine) to
      seriously immunocompromised patients, little has been reported regarding effects
      of AZT on specific immune functions. This study analyzed the in vitro effect of
      AZT on normal human lymphocyte cytolytic activity. AZT at concentrations up to
      100 microM had no effect when added directly to cytotoxicity assays with
      lymphocyte effector cells and natural killer (NK)-sensitive or NK-resistant
      target cells. In contrast, addition of AZT to lymphocytes cultured for 4-10 days
      with interleukin-2 (IL-2) prior to cytotoxicity assays produced a concentration-
      and time-dependent inhibition; this effect was not mimicked by acyclovir or
      ganciclovir. Lymphocyte cell numbers and viability were not reduced in parallel
      to inhibition of cytolytic activity by AZT. Furthermore, AZT inhibition of IL-2
      dependent cytolytic activity was not correlated with alterations in lymphocyte
      cell surface phenotypes by flow cytometry, and lymphocyte culture supernatant
      levels of interferon-gamma were not reduced by AZT. These results suggest that
      AZT may selectively inhibit human lymphocyte functions and thus may have
      implications for long-term therapeutic administration of AZT in chronic
      immunodeficiency states.

PMID- 1989640
TI  - Cholesterylsuccinyl-N-hydroxysuccinimide as a cross-linking agent for the
      attachment of protein to liposomes.

PMID- 1989639
TI  - Hyposmolarity-sensitive release of taurine and free amino acids from human
      lymphocytes.
AB  - This study has shown that human lymphocytes possess a hyposmolarity-sensitive
      release of FAA, particularly of the most abundant one, taurine. This release may
      contribute to the volume regulatory decrease in lymphocytes.

PMID- 1989641
TI  - Studies on the mechanism of induction of microsomal cytochrome P452 and
      peroxisomal bifunctional enzyme mRNAs by nafenopin in primary cultures of adult
      rat hepatocytes.
AB  - The amount of the two mRNAs although lower in cultured hepatocytes than in
      freshly isolated cells was found to be rapidly inducible upon the addition of 32
      microM nafenopin. The induction of cyt.P452 mRNA always preceded the induction of
      PBE mRNA, but for both, the maximal induction (10-20-fold over control) was
      obtained within 24 hr and was achieved by transcriptional activation. At early
      time points (1 and 2 hr after the addition of nafenopin), in the absence of on
      going protein synthesis, the amount of cyt.P452 mRNA (and not of PBE mRNA) was
      transiently higher in the presence of cycloheximide and nafenopin than in the
      presence of nafenopin alone.

PMID- 1989642
TI  - Platelet-activating factor (PAF) antagonist WEB 2086 does not modulate the
      cytotoxicity of PAF or antitumour alkyl lysophospholipids ET-18-O-methyl and SRI
      62-834 in HL-60 promyelocytic leukaemia cells.

PMID- 1989643
TI  - Tumor necrosis factor-alpha, transforming growth factor-beta, and
      tetradecanoylphorbol acetate: competence factors for ML-1 human myeloblastic
      leukemia cell differentiation.
AB  - ML-1 human myeloblastic leukemia cells, suspended in RPMI-1640 medium,
      differentiated to monocyte or macrophage-like cells when either tumor necrosis
      factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta), or
      tetradecanoylphorbol acetate (TPA) was added prior to or simultaneously with
      fetal bovine serum (FBS). When FBS was applied first, and followed, after
      washing, by the cytokines or by TPA, maturation did not occur. A 77 kDa
      glycoprotein (DF77), isolated from human leukocyte-conditioned medium and present
      in FBS, was capable of replacing FBS for induction of differentiation. Thus, in
      this cell system, TNF-alpha, TGF-beta, and TPA acted as competence factors,
      whereas DF77 acted as the progression signal. Optimal competence was established
      after exposure of the cells to TPA or to either of the cytokines for
      approximately 2 or 30 min, respectively. After removal of the factors, competence
      was retained for approximately 3 hr before it declined. These results demonstrate
      that the initiation of ML-1 human myeloblastic leukemia cell differentiation
      relied upon the sequential and ordered input of competence and progression
      signals.

PMID- 1989644
TI  - A novel detection system for submicroscopic human metastases in athymic mice.
AB  - We developed a sensitive assay system to accurately detect the amount of human
      tumor DNA, if present, in athymic mouse organs. Genomic DNA was prepared from a
      human lung carcinoma cell line and from athymic mouse lungs (tumor-bearing and
      non-tumor bearing). Mixtures and dilutions of extracted DNA were slot-blotted
      onto nylon filters and probed with labeled, human-specific Alu sequences. The
      equivalent of one human cell per 2000 mouse cells could be detected using this
      assay. This sensitive assay may now be used to confirm the presence or absence of
      human neoplasm metastases in the athymic mouse model system.

PMID- 1989645
TI  - Antibody-mediated delivery of tumor necrosis factor (TNF-alpha): improvement of
      cytotoxicity and reduction of cellular resistance.
AB  - Recombinant human tumor necrosis factor-alpha (TNF-alpha) is a macrophage
      derived, non-glycosylated (17 kDa) peptide that has a remarkably broad range of
      biological and immunological effects including antiviral action and cytotoxic and
      cytostatic effects. TNF-alpha was coupled to murine antibody ZME-018, which
      recognizes a 240 kDa glycoprotein present on over 80% of melanoma cells. The
      crosslinking was accomplished using the heterobifunctional crosslinking reagent,
      N-succimindyl 3-(2-pyridyldithio)proprionate (SPDP). After purification on gel
      permeation and affinity columns, the resulting eluate was analyzed by non
      reducing SDS-PAGE, which confirmed that the product was a mixture of ZME-018
      coupled to one or two TNF-alpha molecules. The ZME-TNF conjugate was titered
      against murine L-929 cells to demonstrate the presence of active TNF. ELISA of
      the conjugate against target BRO human melanoma cells or non-target T-24 cells
      demonstrated specific binding only to target cells. Melanoma BRO cells were
      killed by the immunoconjugate (IC50 of 10 units/mL), whereas native TNF-alpha had
      no effect at concentrations greater than 50,000 units/mL. The immunoconjugate and
      TNF-alpha were inactive against T-24 non-target cells. These studies suggest that
      the sensitivity of cells to TNF was dramatically augmented by specific antibody
      mediated delivery to tumor cells.

PMID- 1989646
TI  - The role of the clinical editor.

PMID- 1989648
TI  - Expression of ecto-5'-nucleotidase (CD73) in normal mammary gland and in breast
      carcinoma.
AB  - Ecto-5'-nucleotidase (ecto-5'-NT) is a phosphatidylinositol anchored membrane
      structure recently defined as the lymphocyte differentiation antigen CD73. Using
      CD73 (1E9.28.1) monoclonal antibody, normal mammary gland and breast carcinoma
      were immunohistochemically investigated for ecto-5'-NT expression. In normal
      breast epithelium, CD73 was differentially expressed in lobular, ductal and
      myoepithelial cells and was most frequently detected in the myoepithelial
      compartment. The glandular stroma contained fibrocytes, a subset of which was
      also CD73-positive. Among 102 unselected breast carcinoma primary lesions, only 9
      contained CD73-positive tumour cells, whereas in 95 cases, stromal fibroblasts
      and fibrocytes showed variable degrees of CD73 expression. The extent of stromal
      CD73 expression correlated positively with the estrogen receptor (ER) status of
      the tumour (P less than 0.038). We conclude that ecto-5'-NT-expression reflects a
      still unknown state of activity of normal breast epithelium which is lost in the
      majority of carcinomas derived therefrom. It may also be indicative of some
      functional activity of stromal fibroblasts which is significantly enhanced in ER
      positive carcinomas.

PMID- 1989647
TI  - A comparison of the growth promoting properties of ascitic fluids, cyst fluids
      and peritoneal fluids from patients with ovarian tumours.
AB  - The growth promoting properties of ascitic fluids, cyst fluids and peritoneal
      fluids from patients with ovarian malignancy, benign ovarian tumours and non
      tumour related gynaecological conditions have been investigated using an ovarian
      carcinoma cell line (OAW 42), mesothelial cells (58MC) and rat kidney cells (NRK
      49F). Colony stimulating activity (CSA) for tumour cells and transforming
      activity (TA) for mesothelial cells were weakly correlated, but whereas elevated
      TA was tumour-associated, CSA was not. However, TA was not cancer-associated and,
      although the difference between the mean TA values of benign and malignant cyst
      fluids was of borderline significance, some benign cyst fluids from cystadenomas
      showed high TA values. Higher levels of TA in the cystadenomas showed a
      significant correlation with the menopausal status of the patient and higher
      levels of TA in the malignant cyst fluid/peritoneal fluid groups were associated
      with more advanced disease. Results indicated that some fluids contained TGF-beta
      like activity, but there was no direct evidence for the presence of TGF-alpha/EGF
      like activity in the fluids. Heparin inhibited clonogenic growth of tumour cells
      but not mesothelial cells. The reduced CSA which was observed after treatment of
      fluids with both heparin and thrombin implicated coagulation factors in the
      manifestation of CSA. It was concluded that CSA in the fluids was due, at least
      partly, to fibrin coagulation, and TA was due to unknown growth factor(s) which
      may include TGF-beta-like activity. The results are discussed in the context of
      the aetiology of ovarian carcinoma, and the possible clinical significance of TA.

PMID- 1989649
TI  - Flow cytometric evaluation of hypoxic cells in solid experimental tumours using
      fluorescence immunodetection.
AB  - Numerous methods have been proposed for the detection of hypoxic cells using
      nitroimidazoles labelled with both radioactive and stable isotopes where the
      isotopic label becomes bound as a result of reductive metabolism of the nitro
      group. A new probe for hypoxia, 7-(4'-(2-nitroimidazol-l-yl)-butyl)-theophylline,
      is described where an immunologically recognisable hapten (theophylline) is
      covalently linked to a 2-nitroimidazole. Bioreduction of the nitroimidazole leads
      to binding of bioreductive metabolites, and hence the theophylline side-chain, to
      intracellular molecules. Immunochemical procedures are then used to stain cells
      containing the bound theophylline using an FITC-conjugated anti-serum. Flow
      cytometric analysis of stained cells is facilitated by co-staining cellular DNA,
      which allows discrimination of single cells in the sample and rejection of cell
      clumps and debris. The alternative use of an immunoperoxidase-conjugated anti
      serum has been used to demonstrate the localisation of hypoxic cells in frozen
      tumour sections.

PMID- 1989650
TI  - Non-Hodgkin's lymphoma presenting with extradural spinal cord compression:
      functional outcome and survival.
AB  - Between 1971 and 1988, 20 patients with previously undiagnosed non-Hodgkin's
      lymphoma (NHL), of intermediate or high grade histology presented with extradural
      spinal cord compression. All had decompressive surgery. The first treatment after
      surgery was chemotherapy in nine and radiotherapy in 11 patients. At presentation
      15% were ambulant and this improved to 55% after surgery; urinary continence
      improved from 30 to 80%. Mobility and sphincter control remained unchanged,
      regardless of subsequent therapy. Chemotherapy as the initial treatment modality
      after surgery, either alone or in combination with radiotherapy, did not
      jeopardise functional outcome. Mobility after surgery was an independent
      prognostic factor for survival, when corrected for age and stage at presentation
      (P = 0.04). The treatment of intermediate and high grade NHL presenting with
      spinal cord compression should be based on histology, extent of disease and age,
      as with other sites of presentation, but should also take into consideration the
      prognostic importance of post-surgical mobility.

PMID- 1989651
TI  - Prognostic implication of transforming growth factor alpha in adenocarcinoma of
      the lung--an immunohistochemical study.
AB  - We examined for transforming growth factor alpha (TGF alpha) in
      adenocarcinomatous lesions of the lung tissues excised from 138 patients, with
      use of the avidin-biotin-peroxidase complex (ABC) method. TGF alpha was present
      in the cytoplasm of the adenocarcinoma. Our objective was to determine if TGF
      alpha could serve as a prognostic parameter. We divided 138 patients into two
      groups according to the concentration of TGF alpha. Ninety-two patients had a
      high concentration of TGF alpha, in over 75% of the tumour cells, while 46 had a
      low concentration, that is in less than 75% of the cells. The 5-year survival
      rates of patients with high TGF alpha and low TGF alpha were 39% and 64%,
      respectively (P less than 0.05). Our data suggest that evidence of a high
      immunoreactivity of TGF alpha can serve as a prognostic parameter in
      adenocarcinoma of the lung.

PMID- 1989652
TI  - In vivo uptake of 131I-5-iodo-2-deoxyuridine by malignant tumours in man.

PMID- 1989654
TI  - Epidemiology of adenocarcinomas of the small intestine: is bile a small bowel
      carcinogen?
AB  - Using pathology reports and other data from the Cancer Surveillance Program, the
      population-based cancer registry of Los Angeles County, we evaluated demographic
      characteristics and the detailed subsite distribution of adenocarcinomas of the
      small intestine for the period 1972-1985. The most striking finding was the great
      preponderance of these tumours in the duodenum, especially in comparison with
      other histologic types of small bowel cancers. Fifty percent of all small
      intestinal adenocarcinomas occurred at this location, even though the duodenum
      comprises just 4% of the entire length of the small bowel. Furthermore, after
      excluding those cases occurring in the duodenum but with indeterminate subsite,
      57% of these duodenal primaries could be mapped to the 2nd portion of the
      duodenum, a six to seven centimeter segment containing the Ampulla of Vater. We
      could pinpoint the location for 48 of the 77 tumours (62%) occurring in this
      segment, specifically to areas adjacent to the Ampulla. We also confirmed the
      high male to female ratio of small bowel adenocarcinomas in blacks and non-Latino
      whites, but could find no evidence of such an effect in Latinos or Asians;
      however, the number of cases was not large in these latter two racial-ethnic
      groups.

PMID- 1989653
TI  - Association of INT2/HST1 coamplification in primary breast cancer with hormone
      dependent phenotype and poor prognosis.
AB  - The human proto-oncogene INT2 (homologous to the mouse INT2 gene, implicated in
      proviral induced mammary carcinoma) has been mapped to chromosome 11q13 and found
      to share band localisation with, among others, the HST1 proto-oncogene. Both
      genes are members of the fibroblast growth factor family. In the present study,
      coamplification (2-15 copies) of the INT2/HST1 genes was found in 27 (9%) of 311
      invasive human breast carcinomas using slot blot and Southern blot analyses.
      Amplification was not correlated to tumour size, axillary lymph node status or
      stage of disease, neither to patient age nor menopausal status. However, 26 (96%)
      of the 27 amplified tumours were, often strongly, Oestrogen receptor positive
      compared to 65% of the unamplified cases (P = 0.001). These findings are in sharp
      contrast to the strong correlations of HER-2/neu proto-oncogene amplification
      with advanced stage and steroid receptor negativity, previously observed in the
      same series of tumours. Patients with INT2/HST1 amplified breast cancer had a
      significantly shorter disease-free survival compared to those with unamplified
      genes (P = 0.015, median follow up 45 months). This correlation was confined to
      node-negative patients and persisted in multivariate analysis. No significant
      correlation to survival from breast cancer was found. It is concluded that
      amplification of the 11q13 region in breast cancer occurs in a particular subset
      of aggressive tumours, quite different from that identified by HER-2/neu
      amplification. It still remains to be shown that the selection for amplified
      genes at 11q13 is due to the activity of INT2, HST1 or yet another, still
      unidentified, neighbouring gene. However, the results are potentially of clinical
      value in separating a group of node-negative breast cancer for more intense
      treatment.

PMID- 1989655
TI  - LHRH analogues in breast cancer: clever, but do we need them?

PMID- 1989657
TI  - Season of initial detection in breast cancer.

PMID- 1989656
TI  - Association between chemotherapy response and rate of disease progression in
      disseminated melanoma.
AB  - Fifty-five evaluable patients with disseminated malignant melanoma were treated
      with the combination of dacarbazine (DTIC) 400 mg i.v. on days 1 to 3 and
      lomustine (CCNU) 50 to 80 mg m-2 orally on day 1 with intervals of 6 weeks as the
      first line chemotherapy. Three (5%) patients had complete and 6 (11%) partial
      response, and 7 (13%) patients had stable disease at least for 3 months. The
      patients with an objective response (n = 9) survived longer than the rest of the
      patients if the length of survival was calculated from the start of chemotherapy
      (P = 0.0006). However, the responding patients also had longer time interval from
      the diagnosis to the detection of distant metastases (P = 0.05), and survival
      time from disease progression following DTIC and CCNU therapy (P = 0.005). These
      findings suggest that patients with an objective response to DTIC-CCNU therapy
      have melanoma with a slow progression rate, and prolonged survival in such
      patients may in part result from the less aggressive biological nature of their
      tumours.

PMID- 1989658
TI  - Carboplatin and renal function in children.

PMID- 1989659
TI  - Ototoxicity of cisplatinum.

PMID- 1989660
TI  - Lung cancer and passive smoking.

PMID- 1989661
TI  - Characterisation of adriamycin- and amsacrine-resistant human leukaemic T cell
      lines.
AB  - Cell lines resistant to adriamycin and amsacrine were derived from cloned
      sublines of the human T cell line Jurkat. Most of the lines resemble atypical MDR
      cells (Danks et al., 1987; Beck et al., 1987). Thus, resistant Jurkat sublines
      were cross resistant to several topoisomerase II inhibiting drugs but had low or
      no resistance to other classes of drugs, resistance was not reversed by
      verapamil, Pgp was not overexpressed, and drug accumulation was unaltered in
      resistant compared to parental (control) sublines. Other findings were that
      anthracycline metabolism differed between resistant and parental sublines, and
      that resistant sublines displayed altered expression of small polypeptides (less
      than 20K MW) and an 85K MW protein. Drug resistant cells showed resistance to the
      production of drug induced cytogenetic aberrations, DNA breaks, and protein-DNA
      complexes. Resistance was not mediated by altered binding of drugs to DNA or by
      increased repair of DNA damage. Indirect evidence suggests that the resistant
      cells had an altered drug-DNA-topoisomerase II association. The study highlights
      the complex relationships between DNA breaks, cytogenetic aberrations, protein
      DNA complexes and drug cytotoxicity, and shows that the relationships differ for
      adriamycin and amsacrine, suggesting some differences in the modes of action
      and/or resistance for the drugs and cell lines.

PMID- 1989662
TI  - Flavone acetic acid--an interesting novel therapeutic agent or just another
      disappointment?

PMID- 1989663
TI  - Superior localisation and imaging of radiolabelled monoclonal antibody E48
      F(ab')2 fragment in xenografts of human squamous cell carcinoma of the head and
      neck and of the vulva as compared to monoclonal antibody E48 IgG.
AB  - Monoclonal antibody (MAb) E48 and its F(ab')2 fragment, radiolabelled with 131I,
      were tested for tumour localisation and imaging in nude mice bearing a squamous
      cell carcinoma xenograft line derived from a head and neck carcinoma (HNX-HN) or
      from a vulva carcinoma (VX-A431). MAb IgG or F(ab')2 fragments were injected in
      parallel and at day 1, 2, 3 and 6 or 7, mice were either scanned with a gamma
      camera or dissected for determination of isotope biodistribution. In HNX-HN
      bearing mice, E48 IgG as well as F(ab')2 showed highly specific localisation in
      tumour tissue. The mean tumour uptake (n = 4) expressed as the percentage of the
      injected dose per gram of tumour tissue (percentage ID/g) of IgG was 11.9% at day
      1 and increased to 14.6% at day 6 whereas percentage ID/g of F(ab')2 was 7.2% at
      day 1 and decreased during subsequent days. Tumour to blood ratios (T/B) at day 1
      were 1.2 for IgG and 13.6 for F(ab')2 and reached a maximum at day 6 with values
      of 6.4 and 54.2 respectively. In VX-A431 bearing mice, only E48 F(ab')2 showed
      preferential localisation in tumour tissue. At day 1, Percentage ID/g of IgG was
      3.7 and T/B was 0.3, while percentage ID/g of F(ab')2 was 2.4 and T/B was 3.2.
      Percentage ID/g decreased after day 1 while T/B increased. In these experiments
      no preferential localisation of either isotype matched 125I-labelled control IgG
      or F(ab')2 was observed. In F(ab')2 injected HNX-HN bearing mice as well as VX
      A431 bearing mice, tumours could be visualised at day 1 and 2 without any
      appreciable background activity. With MAb IgG this was also possible in HNX-HN
      bearing mice (but not in VX-A431 bearing mice) but only at day 3 and 6. These
      findings suggest that the superior tumour to non-tumour ratios render the E48
      F(ab')2 fragment more qualified for specific targeting of radioisotopes to tumour
      xenografts in this experimental setting.

PMID- 1989664
TI  - Glutathione diminishes the anti-tumour activity of 4-hydroperoxycyclophosphamide
      by stabilising its spontaneous breakdown to alkylating metabolites.
AB  - Evidence was obtained showing that GSH protects against the cytotoxicity of 4
      hydroperoxycyclophosphamide (4-OOH-CP) by minimizing the spontaneous fission of 4
      hydroxycyclophosphamide (4-OH-CP), its breakdown product, to the ultimate toxic
      species, phosphoramide mustard (PM). This conclusion was borne out in two series
      of experiments. The first demonstrated that 4-OH-CP was progressively more stable
      in aqueous solutions containing increasing concentrations of GSH. The second
      series of experiments were carried out with tumour cell lines with high (SKOV-3)
      and low (KHT) GSH contents. The cytotoxicity of 4-OOH-CP, a stable precursor that
      rapidly gives rise to 4-OH-CP spontaneously under physiological conditions, was
      enhanced in GSH-depleted SKOV-3 cells, but was unchanged in GSH-depleted KHT
      cells. It is concluded that the high GSH content of SKOV-3 cells provides a
      significant protection against 4-OH-CP by limiting the breakdown/activation of 4
      OH-CP. Deschloro-4-hydroperoxycyclophosphamide (deschloro-4-OOH-CP), an analogue
      of 4-OOH-CP that generates acrolein (AC) but not PM in the spontaneous fission
      reaction, is essentially non-toxic when compared with 4-OOH-CP but is equally
      potent in depleting GSH. It is postulated that AC may promote the cytotoxicity of
      the parent 4-OH-CP by depleting cellular GSH. Consequently, the stabilising
      influence of GSH on 4-OH-CP is removed, leading to increased formation of PM, the
      ultimate cytotoxic agent.

PMID- 1989666
TI  - Synthetic oligonucleotides as therapeutic agents.

PMID- 1989665
TI  - Anti-tumour activity of flavone acetic acid (NSC 347512) in mice--influence of
      immune status.
AB  - Flavone acetic acid (FAA) is a synthetic flavonoid with dramatic pre-clinical
      anti-tumour activity involving a vascular component in its mechanism but no
      clinical effects have been seen to date. As FAA also has immunomodulatory
      activity, immunological factors might explain differences in activity between
      mouse and man. This study examines the influence of host immune status on the
      anti-tumour activity of FAA. Two human colon tumour xenografts (COBA, HT-29) fail
      to respond to FAA in nude mice. The lack of activity of FAA against HT-29
      xenografts cannot be explained on the basis of limited drug bioavailability as
      achievable plasma, and tumour levels of FAA are similar to those seen in
      sensitive murine colon tumours. The immune status of the host also influences the
      activity of FAA against two transplantable tumours of the mouse colon. Both these
      tumours are highly responsive to FAA in their normal NMRI hosts, but neither
      tumours exhibited significant growth delay in thymectomised NMRI or nude hosts.
      Histological examination of treated tumours revealed significant areas of
      haemorrhagic necrosis in all three hosts. These data suggest a clear
      immunological component in the mechanism of action of FAA which is separate from
      the previously described haemorrhagic necrosis.

PMID- 1989667
TI  - Pancreatobiliary diversion enhances experimental pancreatic carcinogenesis.
AB  - Since compensatory hyperplasia promotes experimental carcinogenesis in the gut,
      we tested the ability of two surgical models of pancreatic growth to promote
      pancreatic carcinogenesis. Male Wistar rats (n = 60) weighing 250-300 g underwent
      pancreatobiliary diversion (PBD), 90% small bowel resection (PSBR) or triple
      transection and reanastomosis of the small intestine (controls). Postoperatively,
      each group received azaserine (20 mg kg-1 wk-1 i.p.) for 6 weeks. Surviving rats
      were killed at 6 months, pancreatic wet weight was measured and histological
      sections were examined for atypical acinar cell foci (AACF), the putative
      precursor of carcinoma. Median relative pancreatic weight (mg pancreas/g body
      weight) was 2.20 for controls (n = 18), 4.08 for PSBR (n = 11) (P less than
      0.001) and 6.86 for PBD (n = 16) (P less than 0.001). PSBR did not affect the
      development of acidophilic AACF, but PBD produced an enormous increase in their
      number per cm3 (median 96 vs. 0; P less than 0.001) and a 7-fold increase in
      their volume (P less than 0.001). Both operations cause pancreatic growth, but
      only PBD promotes carcinogenesis, possibly because of its unique hormonal effect.

PMID- 1989668
TI  - Differential efficacy of flavone acetic against liver versus lung metastases in a
      human tumour xenograft.
AB  - A human ovarian carcinoma, IGROV-1, was xenografted into different sites (i.p.,
      s.c., i.v., and intrasplenically) in nude athymic female mice to investigate the
      pattern of antitumour efficacy of FAA and compare it to that of doxorubicin and
      cisplatin, two established cytotoxic drugs. Ascitic and lung-growing tumours
      totally failed to respond to FAA, whereas s.c. and liver-growing tumours were
      significantly growth inhibited. This pattern of activity differs from that
      achieved by the two conventional cytotoxic drugs, which were active against the
      IGROV-1 tumour growing in all of the tested sites. These studies indicate that
      cytotoxicity is not the major determinant of FAA antitumour efficacy even against
      human tumour xenografts. Moreover, the dramatic difference between the
      sensitivity of lung and liver tumour colonies demonstrates the great importance
      of the site of tumour growth for FAA efficacy.

PMID- 1989669
TI  - Photosensitising potency of structural analogues of benzoporphyrin derivative
      (BPD) in a mouse tumour model.
AB  - The in vivo characteristics of four analogues of benzoporphyrin derivative (BPD)
      have been investigated. Biodistribution data obtained in DBA/2J mice with BPD-MA
      (monoacid ring A analogue) which had been tritiated or internally labelled with
      14C showed that both labelled materials acted in an essentially identical manner
      during the period of study. Biodistribution and clearance studies showed that
      relative distribution in a variety of mouse tissues was similar for all BPD
      analogues. M1 tumour cells (rhabdomyosarcoma in DBA/2J mice) taken from tumours
      excised from animals treated 3 h earlier with BPD, and tested in vitro for
      photosensitivity provided evidence that significant levels of photosensitiser
      detected in tumour was both active and associated with tumour cells. The monoacid
      forms of BPD were found to be much more photodynamically active in this test than
      were the diacid analogues. The ability of the analogues to ablate tumours in mice
      by photodynamic therapy was also tested. Again, BPD-MA and BPD-MB proved to be
      measurably better than the diacid analogues. These findings are discussed in
      reference to structural and physical differences between the analogues.

PMID- 1989670
TI  - Identification of genes controlling metastatic behaviour.

PMID- 1989671
TI  - Stability of critical genetic lesions in human colorectal carcinoma xenografts.

PMID- 1989672
TI  - Manipulation of body fat composition with sterculic acid can inhibit mammary
      carcinomas in vivo.
AB  - Sterculic acid, a delta-9-desaturase inhibitor, administered to rats caused a
      rise in the stearic:oleic acid ratio of total lipids in peripheral red cells,
      serum and liver (P less than 0.001). As a reduction in the stearic:oleic acid
      ratio has been described in cancer cells, we investigated the effect of sterculic
      acid on tumour growth. Female F344 rats were injected subcutaneously with two
      different doses of sterculic acid for 4 weeks prior to, and 4 weeks following,
      implantation of a nitrosomethylurea-induced mammary tumour. Tumour growth was
      inhibited equally by the two doses of sterculic acid (P less than 0.001). A rise
      in the stearic:oleic acid ratio of tumours was observed in rats treated for only
      16 days with sterculic acid. Manipulation of the tissue stearic:oleic acid ratio
      inhibits transplanted mammary tumour growth in rats.

PMID- 1989673
TI  - Rat liver polysome N alpha-acetyltransferase: isolation and characterization.
AB  - Rat liver polysome N alpha-acetyltransferase has been purified to homogeneity by
      a four-step procedure that utilizes ammonium sulfate precipitation, gel
      filtration, hydroxylapatite chromatography, and Mono Q ion exchange
      chromatography. The enzyme is greatly stabilized by the inclusion of EDTA and
      0.01% deoxycholate in the isolation buffers. The purified enzyme has a native
      molecular weight of 190,000 and a subunit molecular weight of 95,000, suggesting
      that it is a homodimer. The enzyme shows a pH optimum of 8.0 and is strongly
      inhibited by Cl-, I-, SCN-, and ClO4- and to a lesser degree by sulfate and
      acetate. It is unaffected by phosphate, citrate, and F- and by Na+ and K+; NH4+
      is partially inhibitory. The enzyme is also sensitive to iodoacetic acid. It is
      generally more similar to yeast N alpha-acetyltransferase [Lee, F.-J. S., Lin, L.
      W., & Smith, J. A. (1988) J. Biol. Chem. 263, 14948-14955] than to the hen
      oviduct enzyme, which contains a 7S RNA subunit [Kamitani, K., & Sakiyama, F.
      (1989) J. Biol. Chem. 264, 13194-13198], although the amino acid compositions are
      quite different.

PMID- 1989675
TI  - Inactivation of gastric and pancreatic lipases by diethyl p-nitrophenyl
      phosphate.
AB  - Reacting gastric and pancreatic lipases with mixed diethyl p-nitrophenyl
      phosphate/bile salt micelles resulted in a stoichiometric inactivation of these
      enzymes as tested on emulsified tributyroylglycerol and trioleoylglycerol as
      substrates. Diethyl p-nitrophenyl phosphate treated gastric lipases were also
      inactive on water-soluble p-nitrophenyl acetate, whereas the modified pancreatic
      lipase was still able to hydrolyze this water-soluble substrate. The binding of
      diethyl p-nitrophenyl phosphate modified pancreatic and gastric lipases to
      tributyroylglycerol/water interface was comparable to that of native lipases. The
      essential free sulfhydryl group of gastric lipases underwent no chemical changes
      due to the reaction with micellar diethyl p-nitrophenyl phosphate. All in all,
      these results indicate that, in both gastric and pancreatic lipases, the
      essential serine residue which was stoichiometrically labeled by this
      organophosphorus reagent is involved in catalysis and not in lipid binding.

PMID- 1989674
TI  - Detection and characterization of intermediates in the folding of large proteins
      by the use of genetically inserted tryptophan probes.
AB  - L-Lactate dehydrogenase from Bacillus stearothermophilus was rebuilt by using
      site-directed mutagenesis to produce an enzymically active, tryptophan-less
      enzyme by replacing all the wild-type tryptophans (80, 150, and 203) by
      tyrosines. Nine single tryptophan-containing active enzymes were constructed from
      this enzyme by genetically replacing one of the tyrosines 36, 85, 147, 190, 203,
      237, 248, 279, or 285 by tryptophan. The equilibrium and the time-resolved
      tryptophan fluorescence intensity and anisotropy were used to report unfolding
      events in guanidine hydrochloride (GHCl) monitored from these nine defined
      positions. Three structural transitions, half complete at 0.55, 1.7, and 2.8 M
      GHCl, were identified and defined four folding intermediates, I (native), II
      (expanded monomer 1), III (expanded monomer 2), and IV (random coil), stable at
      0, 1, 2.2, and 4 M GHCl, respectively. Intermediate II is a globular monomer. All
      the probed alpha-helices and most of the beta-structure was intact. There was an
      increase in the rate but not the extent of the mobilities of six of the probed
      tryptophan side chains, indicating loss of tertiary structure. Circular dichroism
      (CD) showed all the secondary structure to be intact. Intermediate III is
      monomeric and still globular, but the tryptophan anisotropy indicated an increase
      mobility at positions 36, 85, 190, 203, 279, and 285. Helix alpha-B is further
      disrupted but helices alpha-1F, alpha-2G, and alpha 3G were still rigid. CD
      showed half the secondary structure to be still intact. Intermediate IV is a
      random coil in which all tryptophans have complete rotational freedom and the
      helix CD signal is lost.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1989676
TI  - Site-directed alteration of four active-site residues of a pyruvoyl-dependent
      histidine decarboxylase.
AB  - Site-directed mutagenesis has been used to examine the chemical roles of four
      active-site residues in histidine decarboxylase (HDC) from Lactobacillus 30a.
      This protein is known to undergo an autoactivation in which chain cleavage
      between serines-81 and -82 leads to cofactor (pyruvoyl) formation at position 82.
      Conversion of Ser-81 to Ala virtually eliminates productive cleavage. It is
      proposed that the residue plays a key role in stabilizing the transition state of
      the chain cleavage reaction. Conversion of Phe-83 to Met renders the proenzyme
      thermally less stable than wild type and appears to slightly increase the rate of
      autoactivation. The Km value for histidine is increased about 8-fold, confirming
      crystallographic evidence that Phe-83 is involved in substrate binding. Both wild
      type and F83M enzymes show constant Km and steadily increasing kcat values as a
      function of temperature. Lys-155 and Tyr-262, by virtue of their positions in the
      active site of HDC, have been proposed to possibly play specific roles in either
      autoactivation or catalysis by active HDC. Conversion to Gln and Phe respectively
      suggests that these residues have real but minor roles in those processes.

PMID- 1989677
TI  - General base catalysis in a glutamine for histidine mutant at position 51 of
      human liver alcohol dehydrogenase.
AB  - On the basis of the three-dimensional structure of horse liver alcohol
      dehydrogenase determined by X-ray crystallography, His 51 has been proposed to
      act as a general base during catalysis by abstracting a proton from the alcohol
      substrate. A hydrogen-bonding system (proton relay system) connecting the alcohol
      substrate and His 51 has been proposed to mediate proton transfer. We have
      mutated His 51 to Gln in the homologous human liver beta 1 beta 1 alcohol
      dehydrogenase isoenzyme which is expected to have a similar proton relay system.
      The mutation resulted in an about 6-fold drop in V/Kb (Vmax for ethanol oxidation
      divided by Km for ethanol) at pH 7.0 and a 12-fold drop at pH 6.5. V/Kb could be
      restored completely or partially by the presence of high concentrations of
      glycylglycine, glycine, and phosphate buffers. A Bronsted plot of the effect on
      V/Kb versus the pKa of these bases plus H2O and OH- was linear. Only secondary or
      tertiary amine buffers differed from linearity, presumably due to steric
      hindrance. These results suggest that His 51 acts as a general base catalyst
      during alcohol oxidation in the wild-type enzyme and can be functionally replaced
      in the mutant enzyme by general base catalysts present in the solvent. Steady
      state kinetic constants for NAD+ and the trifluoroethanol inhibition patterns
      were similar between the wild-type and the mutant enzyme. Differences in the
      inhibition constants (Ki) of caprate and trifluoroethanol below pH 7.8 and in the
      pH dependence of Ki can be explained by the substitution of neutral Gln for
      positively charged His.

PMID- 1989679
TI  - Structure and expression of the bovine amelogenin gene.
AB  - In order to define further the mechanisms responsible for tooth amelogenin
      heterogeneity, seven bovine amelogenin cDNAs were sequenced. On the basis of
      these sequences, five of the cDNAs could be grouped into one class which differed
      appreciably in sequence from the second group of two cDNAs. Two overlapping
      bovine genomic clones were then isolated and shown by sequencing to contain six
      exons encoding the entire consensus sequence of the class I cDNA. Southern blot
      analysis of DNA from male and female animals using class I or class II specific
      oligonucleotide probes suggested that the class I gene sequence was located on
      the X chromosome while the class II sequence was located on the Y chromosome.
      Therefore, these results also suggest that the genes on the X and Y chromosomes
      are both transcribed. Furthermore, the results are consistent with alternative
      splicing of the class I primary transcript as a potential mechanism for
      generating amelogenin heterogeneity.

PMID- 1989678
TI  - Domain structure of the large subunit of Escherichia coli carbamoyl phosphate
      synthetase. Location of the binding site for the allosteric inhibitor UMP in the
      COOH-terminal domain.
AB  - The large subunit of Escherichia coli carbamoyl phosphate synthetase (a
      polypeptide of 117.7 kDa that consists of two homologous halves) is responsible
      for carbamoyl phosphate synthesis from NH3 and for the binding of the allosteric
      activators ornithine and IMP and of the inhibitor UMP. Elastase, trypsin, and
      chymotrypsin inactivate the enzyme and cleave the large subunit at a site
      approximately 15 kDa from the COOH terminus (demonstrated by NH2-terminal
      sequencing). UMP, IMP, and ornithine prevent this cleavage and the inactivation.
      Upon irradiation with ultraviolet light in the presence of [14C]UMP, the large
      subunit is labeled selectively and specifically. The labeling is inhibited by
      ornithine and IMP. Cleavage of the 15-kDa COOH-terminal region by prior treatment
      of the enzyme with trypsin prevents the labeling on subsequent irradiation with
      [14C]UMP. The [14C]UMP-labeled large subunit is resistant to proteolytic
      cleavage, but if it is treated with SDS the resistance is lost, indicating that
      UMP is cross-linked to its binding site and that the protection is due to
      conformational factors. In the presence of SDS, the labeled large subunit is
      cleaved by trypsin or by V8 staphylococcal protease at a site located 15 or 25
      kDa, respectively, from the COOH terminus (shown by NH2-terminal sequencing), and
      only the 15- or 25-kDa fragments are labeled. Similarly, upon cleavage of the
      aspartyl-prolyl bonds of the [14C]UMP-labeled enzyme with 70% formic acid,
      labeling was found only in the 18.5-kDa fragment that contains the COOH terminus
      of the subunit. Thus, UMP binds to the COOH-terminal domain.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1989680
TI  - Purification and characterization of a gamma-like DNA polymerase from
      Chlamydomonas reinhardtii.
AB  - A crude in vitro system which initiates chloroplast DNA synthesis near the D-loop
      site mapped by electron microscopy [Wu, M., Lou, J. K., Chang, D. Y., Chang, C.
      H., & Nie, Z. Q. (1986) Proc. Natl. Acad. Sci. U.S.A. 83, 6761-6765] consists of
      soluble proteins and proteins extracted from purified thylakoid membrane. In this
      paper, a DNA polymerase activity was purified to near homogeneity from the
      soluble protein fraction of this in vitro system by sequential chromatographic
      separations on heparin-agarose, DEAE-cellulose, and single-stranded DNA-agarose
      columns and sedimentation in a glycerol gradient. In the glycerol gradient, the
      enzyme activity sedimented at a position corresponding to a 110-kDa protein.
      Electrophoretic analysis of the highly purified fraction on SDS-polyacrylamide
      gel revealed a major polypeptide band with an apparent molecular mass of
      approximately 116 kDa. In situ DNA polymerase activity assay shows that the DNA
      polymerization function is associated with the 116-kDa band and an 80-kDa band
      which could be a subunit of the enzyme. Polymerization activity is inhibited by N
      ethylmaleimide, ethidium bromide, and dideoxycytosine triphosphate and is
      relatively resistant to aphidicolin. Poly(dA).(dT)10 and gapped double-stranded
      DNA are preferred templates. The purified enzyme contains no exonuclease activity
      and can initiate DNA replication in a supercoiled plasmid DNA template containing
      the chloroplast DNA replication origin.

PMID- 1989681
TI  - Noncovalent DNA binding of bis(1,10-phenanthroline)copper(I) and related
      compounds.
AB  - The noncovalent DNA binding of the bis(1,10-phenanthroline)copper(I) complex
      [(Phen)2CuI] was examined under anaerobic conditions by absorption and circular
      dichroism spectroscopy, and viscometry, as a function of phenanthroline
      concentration. Analyses according to the McGhee-von Hippel method indicated that
      binding exhibited both neighbor-exclusion and positive cooperativity effects,
      with a neighbor-exclusion parameter n approximately 2 and a cooperativity
      parameter omega approximately 4. The association constant for (Phen)2CuI binding
      decreased with increasing concentration of phenanthroline in excess over that
      required to stoichiometrically generate (Phen)2CuI, indicating that free
      phenanthroline was a weak competitive inhibitor of (Phen)2CuI binding. The
      maximal association constant for DNA binding of (Phen)2CuI in 0.2 M NaCl and 9.8%
      ethanol, extrapolated to zero concentration of excess phenanthroline, was 4.7 x
      10(4) M-1 (DNA base pairs). The magnitude of the neighbor-exclusion parameter,
      the changes in spectral properties of (Phen)2CuI induced by DNA binding, and the
      increase in DNA solution viscosity upon (Phen)2CuI addition are consistent with a
      model for DNA binding by (Phen)2CuI involving partial intercalation of one
      phenanthroline ring of the complex between DNA base pairs in the minor groove as
      suggested previously [Veal & Rill (1989) Biochemistry 28, 3243-3250]. Viscosity
      measurements indicated that the mono(phenanthroline)copper(I) complex also binds
      to DNA by intercalation; however, no spectroscopic or viscometric evidence was
      found for DNA binding of free phenanthroline or the bis(2,9-dimethyl-1,10
      phenanthroline)copper(I) complex. DNA binding of free phenanthroline may be
      cooperative and induced by prior binding of (Phen)2CuI.

PMID- 1989683
TI  - The membrane interaction of amphiphilic model peptides affects phosphatidylserine
      headgroup and acyl chain order and dynamics. Application of the "phospholipid
      headgroup electrometer" concept to phosphatidylserine.
AB  - Deuterium nuclear magnetic resonance (2H NMR) was used to study the interaction
      of amphiphilic model peptides with model membranes consisting of 1,2-dioleoyl-sn
      glycero-3-phospho-L-serine deuterated either at the beta-position of the serine
      moiety ([2-2H]DOPS) or at the 11-position of the acyl chains ([11,11-2H2]DOPS).
      The peptides are derived from the sequences H-Ala-Met-Leu-Trp-Ala-OH (AX, one
      letter code with X = MLWA) and H-Arg-Met-Leu-Trp-Ala-OH (RX+) and contain a
      positive charge of +1 (AXme+) or +2 (RXme2+) at the amino terminus or one
      positive charge at each end of the molecule (AXetN2+). Upon titration of
      dispersions of DOPS with the peptides, the divalent peptides show a similar
      extent of binding to the DOPS bilayers, which is larger than that of the single
      charged peptide. Under these conditions the values of the quadrupolar splitting
      (delta vq) of both [2-2H]DOPS and [11,11-2H2]DOPS are decreased, indicating that
      the peptides reduce the order of both the DOPS headgroup and the acyl chains. The
      extent of the decrease depends on the amount of peptide bound and on the position
      of the charged moieties in the peptide molecule. The effects exerted by the
      peptides on the delta vq value of [2-2H]DOPS are consistent with the PS headgroup
      responding as a molecular electrometer to the surface charge resulting from the
      presence of the peptides in the lipid-water interface. The effects on the acyl
      chain deuterons are in agreement with a localization of the peptides intercalated
      in between the lipid headgrouops.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1989682
TI  - An alkaline phosphatase protection assay to investigate trp repressor/operator
      interactions.
AB  - We have used an alkaline phosphatase protection assay to investigate the
      interaction of the trp repressor with its operator sequence. The assay is based
      on the principle that the trp repressor will protect a terminally 5'-32P-labeled
      operator DNA fragment from attack by alkaline phosphatase. The optimal
      oligonucleotide for investigating the trp repressor/operator interaction extends
      two base pairs from each end of the genetically defined target sequence predicted
      by in vivo studies [Bass et al. (1987) Genes Dev. 1, 565-572]. The assay works
      well over a 10,000-fold range of protein/DNA affinity and is used to show that
      the corepressor, L-tryptophan, causes the liganded repressor to bind a 20 base
      pair trp operator duplex 6400 times more strongly than the unliganded
      aporepressor. The affinity of the trp repressor for operators containing
      symmetrical mutations was interpreted in terms of the trp repressor/operator
      crystal structure as follows: (1) Direct hydrogen bonds with the functional
      groups of G-9 of the trp operator and the side chain of Arg 69 of the trp
      repressor contribute to DNA-binding specificity. (2) G-6 of the trp operator is
      critical for DNA-binding specificity probably because of the two water-mediated
      hydrogen bonds between its functional groups and the N-terminus of the trp
      repressor's E-helix. (3) Sequence-dependent aspects of the trp operator's
      conformation help stabilize the trp repressor/operator complex.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1989684
TI  - Average structural and motional properties of a diunsaturated acyl chain in a
      lipid bilayer: effects of two cis-unsaturated double bonds.
AB  - Isolinoleic acid (18:2 delta 6,9) deuterated at 10 different positions was
      esterified to form 1-palmitoyl-2-isolinoleoyl-sn-glycero-3-phosphocholine
      (PiLPC), and the average structural and motional properties of the diunsaturated
      chain, in aqueous dispersions of PiLPC, were examined by 2H NMR spectroscopy. For
      each sample, 2H spectra were acquired over a temperature range of 1-40 degrees C
      and the quadrupolar splittings interpreted in terms of carbon-deuterium bond
      order parameters, SCD. Furthermore, definition of the average orientation of the
      C8 methylene unit with respect to the bilayer normal [Baenziger, J. E., Smith, I.
      C. P., Hill, R. J., & Jarrell, H. C. (1988) J. Am. Chem. Soc. 110, 8229-8231]
      provided sufficient information to calculate both the average orientations and
      the molecular order parameters, Smol (which reflects the amplitudes of motion),
      for the C6-C7 and the C9-C10 double bonds. The results indicate that both the
      motional freedom (reflected in the order profile) and the average structure
      (reflected in the orientation of carbon segments with respect to the bilayer
      normal) are strongly affected by the presence of two cis-unsaturated double
      bonds. The data were interpreted in terms of two possible models whereby, in each
      case, the chain adopts a conformation consistent with the low-energy conformation
      of 1,4-pentadiene [Applegate, K. R., & Glomset, J. A. (1986) J. Lipid Res. 27,
      658-680] but undergoes a two-site jump between the conformations. The jump motion
      arises mainly from rotations about the C7-C8 and the C8-C9 single bonds that
      disorder the C8 and the C9-C10 segments (Smol = 0.15 and 0.08, respectively) but
      leave the C6-C7 double bond relatively immobile (Smol = 0.55; all at 40 degrees
      C). It is suggested that acyl chains containing three or more double bonds could
      not undergo a similar jump motion and therefore would be highly ordered and not
      "fluid" as is generally thought.

PMID- 1989685
TI  - Low-affinity platelet factor 4 1H NMR derived aggregate equilibria indicate a
      physiologic preference for monomers over dimers and tetramers.
AB  - Low-affinity platelet factor 4 (LA-PF4), unlike another related, sequentially
      homologous (about 50%) platelet-specific protein, platelet factor 4 (PF4), is an
      active mitogenic and chemotactic agent. PF4 exhibits a high binding affinity for
      heparin, while LA-PF4 does not. Both PF4 and LA-PF4 can exist in dimer and
      tetramer aggregate states. Equilibrium constants for PF4 aggregation have
      recently been estimated from fractional populations derived from proton nuclear
      magnetic resonance (NMR) integrals assigned to resonances in monomer, dimer, and
      tetramer states [Mayo & Chen (1989) Biochemistry 28, 9469]. On a 500-MHz NMR time
      scale, relatively slow exchange among LA-PF4 aggregate species has also allowed
      Tyr 15 ring proton resonances to be assigned for monomer, dimer, and tetramer
      states in LA-PF4. As a function of pH and ionic strength, equilibrium association
      constants for LA-PF4 dimer (KD) and tetramer (KT) formation have been estimated
      from Tyr 15 ring proton resonance integrals. At low ionic strength, KD reaches a
      minimum value of 12 M-1 at pH 3 where KT is at its maximum value of 1.6 x 10(5) M
      1. At pH 4.1, KD and KT have the same value, 1.1 x 10(3) M-1, which is the
      minimum value for KT. KD plateaus off to its maximum value of 2.2 x 10(4) M-1 by
      pH 5.5. These values are significantly lower than those for PF4. Analysis of the
      pH dependence of KD and KT suggests that electrostatic interactions probably
      among Glu/Asp and Lys/Arg side chains form the predominant force in the monomer
      monomer binding process, i.e., KD, while like-charge repulsion due to proximal,
      intersubunit Glu/Asp residues decreases KT as the pH is raised. At pH 7 and low
      ionic strength, the dimer state is highly favored over the tetramer state.
      Elevating the solvent ionic strength at pH 7 destabilizes the dimer state. Under
      these more physiologic conditions, i.e., pH 7 and 0.1-0.2 M NaCl, LA-PF4 monomers
      are highly favored over dimers and tetramers. For PF4 under similar solvent
      conditions, tetramers predominate. Differences in biological activities between
      these homologous platelet-specific proteins may be the result, at least in part,
      of differing aggregation properties. The biologically active state for PF4 is
      tetramer, while for LA-PF4 it is monomer. Quaternary structure may, therefore,
      account for strong heparin binding in PF4, most likely by presenting a more
      favorable structural matrix for effective glycosaminoglycan interactions.

PMID- 1989687
TI  - Proteins that bind calcium in a phospholipid-dependent manner.
AB  - Three proteins (Mr = 64K, 32K, and 22K) that bind to phospholipids in a calcium
      dependent manner were purified from bovine brain. The calcium-binding properties
      of these proteins were investigated by equilibrium dialysis and by gel filtration
      chromatography. The 64- and 32-kDa proteins were found to have calcium- and
      phospholipid-binding properties strikingly similar to those of protein kinase C
      [Bazzi, M.D., & Nelsestuen, G.L. (1990) Biochemistry 29, 7624]. The free proteins
      bound limited divalent metal ion even at 200 microM calcium. However, they bound
      eight to nine calcium ions per protein in the presence of membranes containing
      acidic phospholipids. The calcium concentrations needed for protein-phospholipid
      binding were different for these two proteins and were strongly influenced by the
      phospholipid composition of the vesicles; vesicles of higher phosphatidylserine
      content required lower concentrations of calcium for protein-membrane
      association. These properties described a general type of calcium-interacting
      system where simultaneous interaction of all three components (protein,
      phospholipids, and calcium) is required. The free proteins may provide only
      partial coordinate bonds to each calcium ion, but complete calcium-binding sites
      could be generated at the protein-phospholipid interface. In contrast to the 64-
      and 32-kDa proteins, the 22-kDa protein bound similar amounts of calcium (two to
      three ions/protein) in the presence or the absence of phospholipids. The 22-kDa
      protein had the lowest affinity for phospholipid and the highest affinity for
      calcium of the three proteins tested. Thus, calcium-dependent phospholipid
      binding proteins consist of several types. For example, the 64- and 32-kDa
      proteins appear to be quite abundant and may even function as a calcium buffer to
      modulate signaling events.

PMID- 1989686
TI  - Characterization of the kinetic pathway for fibrin promotion of alpha-thrombin
      catalyzed activation of plasma factor XIII.
AB  - Kinetic and thermodynamic studies are presented showing that the cofactor
      activity of fibrin I (polymerized des-A fibrinogen) in the alpha-thrombin
      catalyzed proteolysis of activation peptide (AP) from plasma factor XIII can be
      attributed to formation of a fibrin I-plasma factor XIII complex (Kd = 65 nM),
      which is processed by alpha-thrombin more efficiently (kcat/Km = 1.2 x 10(7) M-1
      s-1) than free, uncomplexed plasma factor XIII (kcat/Km = 1.4 x 10(5) M-1 s-1).
      The increase in the specificity constant (kcat/Km) is shown to be largely due to
      an increase in the apparent affinity of alpha-thrombin for the complex of plasma
      factor XIII and fibrin I, as reflected by the 30-fold decrease in the Michaelis
      constant observed for fibrin I bound plasma factor XIII relative to that for
      uncomplexed plasma factor XIII. Analysis of the initial rates of alpha-thrombin
      catalyzed hydrolysis of fibrinopeptide B (FPB) from fibrin I polymer in the
      presence of plasma factor XIII indicated that alpha-thrombin bound to fibrin I in
      the ternary complex of alpha-thrombin, plasma factor XIII, and fibrin I polymer
      is competent to catalyze cleavage of both FPB from fibrin I and AP from plasma
      factor XIII. This observation is consistent with the view that alpha-thrombin
      within the ternary complex is anchored to fibrin I polymer through a binding site
      distinct from the active site (an exosite) and that the active site is
      alternatively complexed with the AP moiety of plasma factor XIII or the FPB
      moiety of fibrin I. This conclusion is supported by the observation that a 12
      residue peptide, which binds to an exosite of alpha-thrombin and blocks the
      interaction of alpha-thrombin with fibrinogen and fibrin, competitively inhibits
      alpha-thrombin-catalyzed release of both FPB and AP from the fibrin I-plasma
      factor XIII complex.

PMID- 1989688
TI  - Analysis of phi and chi 1 torsion angles for hen lysozyme in solution from 1H NMR
      spin-spin coupling constants.
AB  - Three-bond 3JHN alpha coupling constants have been determined for 106 residues
      and 3J alpha beta coupling constants have been measured for 57 residues of the
      129-residue protein hen egg white lysozyme. These NMR data have been compared
      with torsion angles defined in the tetragonal and the triclinic crystal forms of
      the protein. For most residues the measured 3JHN alpha values were consistent
      with the phi torsion angles found in both crystal forms; the RMS difference
      between the coupling constants calculated by using the tetragonal crystal
      structure phi angles and the experimental 3JHN alpha values is 0.88 Hz. Thus
      there appears to be no significant averaging of the phi torsion angle either in
      the interior or at the surface of the protein. For 41 of the residues where 3J
      alpha beta coupling constants have been determined, the values are consistent
      with a single staggered conformation about the chi 1 torsion angle and there is
      complete agreement between the NMR data in solution and the torsion angles
      defined in the crystalline state. In contrast, for the other 16 residues where 3J
      alpha beta coupling constant values have been measured, the data indicate
      extensive motional averaging about the chi 1 torsion angle. These residues occur
      largely on the surface of the protein and examination of the crystal structures
      shows that many of these residues adopt a different conformation in the triclinic
      and tetragonal crystal forms and have high crystallographic temperature factors.
      It appears, however, that in solution conformational flexibility of the side
      chains of surface residues is significantly more pronounced than in individual
      crystal structures.

PMID- 1989689
TI  - RNA polymerase III transcription of genes that lack internal control regions.

PMID- 1989690
TI  - High-efficiency gene transfection by in situ electroporation of cultured cells.
AB  - It is demonstrated in this study that high-efficiency gene transfection can be
      obtained by directly electroporating cultured mammalian cells in their attached
      state using a pulsed radio-frequency (RF) electric field. A plasmid DNA
      containing the reporter gene beta-gal was introduced into COS-M6 cells and CV-1
      cells using this in situ electroporation method. At the optimal electric field
      strength (1.2 kV/cm), we found that over 80% of the M6 cells took up and
      expressed the beta-gal gene with a cell survival rate of about 50%. In contrast,
      the transfection efficiency was less than 20% when the M6 cells were
      electroporated in suspension. It was shown that CV-1 cells could also be
      electroporated highly efficiently using the in situ method. Furthermore, we have
      measured the time required to express the beta-gal gene after the plasmid DNA was
      introduced. We found that the percentage of cells expressing beta-gal reached a
      peak value about 10 h after electroporation. This time-course was the same for
      both attached and suspended cells, suggesting that the observed difference in
      transfection efficiency was mainly the result of effects of the detachment
      treatment on the electroporation process rather than on the gene expression.

PMID- 1989691
TI  - Regulation of the inducible nitrate reductase isoform from soybeans.
AB  - The activity of the pH 7.5 NADH-linked nitrate reductase isoform from soybeans is
      termed inducible. Activity can be observed only in seedlings which have been
      supplied nitrate. Steady-state levels of mRNA for this isoform also show an
      absolute requirement for nitrate. Nitrate reductase specific mRNA can be observed
      within 2 h after nitrate treatment. Levels peaked 48 h after nitrate treatment,
      while the addition of glutamine to nitrate diminished amounts of nitrate
      reductase specific mRNA. Using nuclear runoff transcription assays, we have shown
      that one level of control of nitrate reductase synthesis is transcriptional.

PMID- 1989692
TI  - Optimized conditions for electrotransformation of bacteria are related to the
      extent of electropermeabilization.
AB  - Electropulsation is a simple and efficient way to introduce cloned genes into a
      variety of cell types, even with walled species. In the case of bacteria, we
      observed no direct correlation between survival rate and transformation yield. In
      the present work, we show that the yield of transformation is directly related to
      the level of the electric-field induced level of cell permeabilization. From
      experiments on Escherichia coli, it was confirmed that the extent of associated
      ATP leakage was a reliable assay. This approach was extended to other strains,
      such as Salmonella typhimurium, which to date had not been electrotransformed by
      plasmids.

PMID- 1989694
TI  - Isolation of an active gene and of two pseudogenes for mouse U7 small nuclear
      RNA.
AB  - Three U7 RNA-related sequences were isolated from mouse genomic DNA libraries.
      Only one of the sequences completely matches the published mouse U7 RNA sequence,
      whereas the other two apparently represent pseudogenes. The matching sequence
      represents a functional gene, as it is expressed after microinjection into
      Xenopus laevis oocytes. Sequence variations of the conserved cis-acting 5' and 3'
      elements of U RNA genes may partly explain the low abundance of U7 RNA.

PMID- 1989693
TI  - A 27-bp deletion is responsible for the expression of a variant CABP1, a cyclic
      AMP-binding protein of Dictyostelium discoideum.
AB  - The two subunits of the cAMP-binding protein CABP1 in V12M2 differ in size from
      their counterparts in strain AX2. Sequence analysis shows that the CABP1 gene of
      V12M2 is missing 27 bp. Results from transfecting experiments provide further
      evidence that both subunits of CABP1 are encoded by the same gene.

PMID- 1989695
TI  - Immunologically-related nucleic acid-binding proteins associated with the nuclear
      matrix of Physarum polycephalum.
AB  - The nuclear matrix of Physarum polycephalum is composed of two abundant
      polypeptides of 27 and 38 kDa as well as numerous minor polypeptides of various
      molecular weight. By contrast, the nuclear matrix of vertebrates consists of
      three major (the lamins) and many minor polypeptides mainly in the 60-70 kDa
      molecular weight range. In order to better characterize the major nuclear matrix
      proteins of P. polycephalum and, perhaps, define their relationship with the
      major nuclear matrix proteins of vertebrates, we have purified the abundant
      nuclear matrix proteins of P. polycephalum. In Western blot analyses, polyclonal
      antibodies raised against the purified 27 kDa polypeptide recognised polypeptides
      of 50 kDa, 45 kDa and several low molecular weight species (14-21 kDa) in the P.
      polycephalum nuclear matrix. The polyclonal antibodies did not react with the
      other abundant nuclear matrix protein of 38 kDa from P. polycephalum nor with
      polypeptides of the mouse nuclear matrix. Two-dimensional gel electrophoresis
      showed that the major nuclear matrix proteins of P. polycephalum were more basic
      than the major nuclear matrix proteins of vertebrates, the lamins. Moreover, both
      the 27 and 38 kDa polypeptides are post-translationally modified by either D
      mannosyl or D-glycosyl moieties, and not by phosphorylation as has been
      demonstrated for the vertebrate lamins. DNA-binding assays further revealed that
      the immunologically related polypeptides of 50 kDa, 45 kDa, 27 kDa and low
      molecular weight species of 14-21 kDa preferentially bound single-stranded DNA,
      but the 38 kDa polypeptide of Physarum matrix did not. Based on these findings,
      we conclude that the abundant nuclear matrix protein of 27 kDa belongs to a group
      of immunologically-related nucleic acid-binding proteins, and is immunologically
      and functionally distinct from the other major nuclear matrix protein of 38 kDa
      from P. polycephalum and the vertebrate lamins.

PMID- 1989696
TI  - Preferential deadenylation of Sarcophaga lectin mRNA during its acute phase
      expression.
AB  - The sizes of mRNAs of various defense proteins of Sarcophaga peregrina (flesh
      fly) were shown to become progressively shorter. We studied the shortening of the
      Sarcophaga lectin mRNA, because this mRNA shows acute phase expression on injury
      of the larvae and programmed expression in the pupal stage. Results showed that
      this mRNA underwent deadenylation when expressed in response to body injury, but
      no appreciable change in size during programmed expression in the pupal stage.
      During acute phase expression, the size of the poly(A) tail of the Sarcophaga
      lectin mRNA decreased from 130 bases to about 30 bases in 6 h. The half-lives of
      the forms with different sizes of poly(A) tail were almost identical.

PMID- 1989697
TI  - A class of amphipathic proteins associated with lipid storage bodies in plants.
      Possible similarities with animal serum apolipoproteins.
AB  - The lipid-storing tissues of plants contain many small (0.2-1 microns) lipid
      (normally triacylglycerol) droplets which are surrounded and stabilized by a
      mixed phospholipid and protein annulus. The proteinaceous components of the lipid
      storage bodies are termed oleosins and are not associated with any other cellular
      structures. The major oleosins of rapeseed and radish have been isolated by
      preparative SDS-PAGE and are respectively classes of 19 kDa and 20 kDa proteins.
      Both protein classes were N-terminally blocked for direct sequencing, but were
      partially sequenced following limited proteolytic digestion. The major rapeseed
      oleosin was made up of at least two 19 kDa polypeptides, termed nap-I and nap-II,
      which have closely related but different amino acid sequences. A single 20 kDa
      oleosin, termed rad-I, was found in radish. A near full length cDNA clone for a
      major rapeseed oleosin was sequenced and found to correspond almost exactly to
      the sequence of nap-II. The sequences of nap-I and rad-I show very close
      similarity to one another, as do the sequences of nap-II and the previously
      determined sequence for the major oleosin from maize. All four oleosins have a
      large central hydrophobic domain flanked by polar N- and C-terminal domains.
      Secondary structure predictions for the four oleosins are similar and a novel
      model is proposed based on a central hydrophobic beta-strand region flanked by an
      N-terminal polar alpha-helix and a C-terminal amphipathic alpha-helix. The
      possibility that oleosins exhibit structural and functional similarities with
      some animal apolipoproteins is discussed.

PMID- 1989699
TI  - Canada's blood collection system should be reorganized, critics say.

PMID- 1989698
TI  - Primary structure of pregnancy zone protein. Molecular cloning of a full-length
      PZP cDNA clone by the polymerase chain reaction.
AB  - A full-length cDNA clone of the human pregnancy zone protein (PZP) was cloned
      from the hepatocellular carcinoma cell line Hep3B. Based on the exon sequences of
      the PZP gene (Devriendt et al. (1989) Gene 81, 325-334; Marynen et al.,
      unpublished data), primer pairs were designed to amplify six overlapping
      fragments of the PZP cDNA. The obtained cDNA is 4609 bp long and contains an open
      reading frame coding for 1482 amino acids, including a signal peptide of 25 amino
      acid residues. Comparison with the published partial PZP amino acid sequence
      (Sottrup-Jensen et al. (1984) Proc. Natl. Acad. Sci. USA 81, 7353-7357) and the
      PZP genomic sequences confirmed the identity as a PZP cDNA. 71% of the
      corresponding amino acid residues in PZP and human alpha 2-macroglobulin (alpha
      2M) are identical and all cysteine residues are conserved. A typical internal
      thiol ester site and a bait domain were identified. A Pro/Thr polymorphism was
      identified at amino acid position 1180, and an A/G nucleotide polymorphism at bp
      4097.

PMID- 1989700
TI  - Bill C-43 and the CMA.

PMID- 1989701
TI  - HIV infection among Quebec women giving birth to live infants.

PMID- 1989703
TI  - Distribution of the CPS.

PMID- 1989702
TI  - Clinical research.

PMID- 1989704
TI  - The animal rights war.

PMID- 1989705
TI  - Wife assault: physicians cannot ignore it.

PMID- 1989706
TI  - Ribavirin: is there a risk to hospital personnel? Infectious Diseases and
      Immunization Committee, Canadian Paediatric Society.

PMID- 1989707
TI  - Helping patients travel by air.
AB  - Although safe and rapid, air travel may present problems for people with certain
      medical conditions. Most medical emergencies that occur during a flight are
      preventable by judicious screening and preparation. We provide guidelines for
      physicians who are consulted about the wisdom of undertaking a journey by air.
      Potential stresses before, during and after the flight are outlined, including
      decreased atmospheric pressure, low humidity, turbulence, inactivity and time
      changes. We recommend precautionary measures for passengers with certain medical
      conditions, such as recent myocardial infarction, pulmonary disorders,
      pneumothorax, cerebrovascular accidents and diabetes and for those who have
      recently had surgery. The policy regarding air travel for pregnant women varies
      with each airline, but for certain conditions associated with pregnancy
      supplemental oxygen should be ordered before the trip. The special equipment and
      care that most airlines offer to ill or disabled people are described.

PMID- 1989708
TI  - Levamisole and 5-fluorouracil therapy for resected colon cancer: a new
      indication.
AB  - OBJECTIVE: To evaluate the benefits and risks of postoperative treatment with
      levamisole plus 5-fluorouracil (5-FU) in patients with colon cancer. DESIGN:
      Computerized searches of MEDLINE and CANCERLIT were performed, and the reference
      list of each retrieved article was checked. Only randomized trials of therapy
      with levamisole alone or combined with 5-FU for colon cancer without distant
      metastases were included. The studies were then evaluated with the use of four
      criteria. RESULTS: We reviewed six randomized trials, of which three satisfied
      our criteria. Two studies demonstrated a significant improvement in the survival
      rate with levamisole plus 5-FU among patients with colon cancer and
      pathologically confirmed metastases to adjacent lymph nodes (Dukes' stage C). A
      subgroup analysis in another study demonstrated a similar benefit. The toxic
      effects of the drugs were generally mild. The three other studies showed no
      difference in survival rates between the treatment groups; however, the samples
      were too small to detect a clinically or statistically important difference.
      CONCLUSIONS: Because many patients with colon cancer will suffer a relapse we
      recommend that they be offered the opportunity to participate in clinical trials
      of adjuvant therapy. For those with stage C disease not entering a clinical trial
      levamisole plus 5-FU is appropriate adjuvant therapy.

PMID- 1989709
TI  - Is perinatal care in southwestern Ontario regionalized?
AB  - OBJECTIVE: To determine whether perinatal care in southwestern Ontario is
      regionalized, to identify trends over time in referral patterns, to quantify
      trends in perinatal death rates and to identify trends in perinatal death rates
      that give evidence of regionalization. DESIGN: Cohort study. SETTING: Thirty-two
      hospitals in southwestern Ontario (1 level III, 1 modified level III and 30 level
      II or I). PATIENTS: All pregnant women admitted to the hospitals and their
      infants. MAIN OUTCOME MEASURES: Antenatal and neonatal transfer status, live-born
      with discharge home alive from hospital of birth, stillborn, and live-born with
      death before discharge. RESULTS: Between 1982 and 1985 the antenatal transfer
      rate increased from 2.2% to 2.8% (p less than 0.003). The proportion of births of
      infants weighing 500 to 1499 g increased from 49% to 69% at the level III
      hospital. The neonatal transfer rate increased from 26.2% to 47.9% (p less than
      0.05) for infants in this birth-weight category and decreased from 10.2% to 7.1%
      (p less than 0.03) for infants weighing 1500 to 2499 g. The death rate among
      infants of low birth weight was lowest among those born at the level III centre
      and decreased at all centres between 1982 and 1985. CONCLUSIONS: Perinatal care
      in southwestern Ontario is regionalized and not centralized; regionalization in
      southwestern Ontario increased between 1982 and 1985.

PMID- 1989710
TI  - Improved endocervical sampling with the Cytobrush.
AB  - OBJECTIVE: To evaluate the effectiveness of the Ayre wooden spatula, the cotton
      tipped swab and the Zelsmyr Cytobrush in obtaining endocervical cells. DESIGN:
      Cross-sectional comparison study. SETTING: Family practice unit. PATIENTS: All
      postpubertal, nonpregnant women who underwent a routine Papanicolaou smear during
      a 7-month period. INTERVENTIONS: The three devices were used in each patient in a
      randomized sequence. An experienced cytotechnologist blinded to the device used
      evaluated the slides for overall epithelial cellularity (graded from 0 [acellular
      specimen] to 12 [overloaded sample]), density (the number of groups of five or
      more endocervical cells) and size of cell clusters (5 to 10 cells per cluster
      [score of 1], 11 to 100 [2] or more than 100 [3]). MAIN RESULTS: Samples from 2
      of the 136 women were rejected because of improper labelling of the slides or
      failure to use all three devices. Seventy-six (57%) of the smears obtained with
      the spatula and 71 (53%) with the swab had no endocervical cells, as compared
      with only 14 (10%) obtained with the Cytobrush (p = 0.001). The overall
      cellularity (and standard deviation [SD]) of the smears obtained with the
      Cytobrush (5.69 [SD 1.17], p = 0.001) and the spatula (5.70 [SD 1.46], p = 0.001)
      was significantly greater than the cellularity of those obtained with the swab
      (4.31 [SD 1.17]). The Cytobrush yielded significantly more groups of endocervical
      cells (109.84 per slide) than either the spatula (4.17) or the swab (6.25) (p =
      0.001). The Cytobrush also produced larger cell clusters (1.56 [SD 0.67], p =
      0.001) than either the swab (0.83 [SD 1.70]) or the spatula (0.64 [SD 0.67]).
      CONCLUSIONS: The Cytobrush and the spatula should be used instead of the spatula
      alone or the spatula and the swab for collecting endocervical cells.

PMID- 1989711
TI  - Estimated burden of diabetes mellitus in Manitoba according to health insurance
      claims: a pilot study.
AB  - OBJECTIVE: To estimate the burden of diabetes mellitus in Manitoba from 1980 to
      1984. DESIGN: Review of the Manitoba Health Services Commission (MHSC) database.
      The validity of the MHSC data was established through two substudies: one
      involved self-reports from a survey of elderly Manitobans, and the other involved
      people with confirmed diabetes enrolled in the provincial diabetes education
      program. SUBJECTS: Sample of 100,000 people stratified by age, sex and MHSC
      health region: 50,000 were aged 25 to 64 years, and 50,000 were aged 65 or more.
      All MHSC claims containing the ICD-9-CM code for diabetes mellitus or gestational
      diabetes were identified. MAIN RESULTS: Of the sample 7627 people were found to
      have a diagnosis of diabetes, the annual prevalence being 0.8% among those 25 to
      44 years of age, 3.5% among those 45 to 64 and 7.6% among those 65 or older. The
      annual incidence rate among those over 25 years of age was 7.8 per 1000. Of the
      4556 pregnant women 25 to 44 years old 85 (1.9%) had diabetes; 23 were believed
      to have gestational diabetes. CONCLUSIONS: The incidence and prevalence rates
      were similar to those determined on the basis of self-reports in Canadian and US
      national surveys. The use of an administrative database such as that of the MHSC
      will provide key information for planning health services for diabetic patients
      and will permit the monitoring of long-term trends in the incidence and
      prevalence of the disease.

PMID- 1989712
TI  - Adverse events temporally associated with immunizing agents: 1988 report.

PMID- 1989714
TI  - Operating room closure in Digby brings rural-recruitment problem into focus.

PMID- 1989713
TI  - Cholesterol-free foods: where's the trans?

PMID- 1989716
TI  - Midwifery's march through the ages.

PMID- 1989715
TI  - Doctor proposes new ethics protocol for Alzheimer's research.

PMID- 1989717
TI  - The computer, CME and the family physician.

PMID- 1989718
TI  - Giving death a helping hand.

PMID- 1989719
TI  - A call for action.

PMID- 1989720
TI  - Case management.

PMID- 1989721
TI  - WHO Code? Who cares?

PMID- 1989722
TI  - Nurses and AIDS.

PMID- 1989723
TI  - Family caregivers.

PMID- 1989724
TI  - Role strain.

PMID- 1989725
TI  - [The child with AIDS].
AB  - Both hospital and community health nurses need to overcome their fears of AIDS
      contagion. Faced with a growing number of children and families affected by AIDS,
      nurses will see their role as health provider change. Working within a
      multidisciplinary health team nurses will become change agents, promoting sound
      physical, mental and sexual health practices among families in their care.

PMID- 1989726
TI  - [Mild psychosomatic illnesses].
AB  - Referring to our August article on psychosomatic illness, the author states that
      there are harmless forms of this disorder that nearly everyone, including nurses,
      experience at some point in their lives. Early awareness is an important step
      toward defusing potentially harmful psychosomatic problems.

PMID- 1989727
TI  - High-performance liquid chromatography as a diagnostic tool in prolonged
      neuromuscular blockade.
AB  - We report the use of high-performance liquid chromatography (HPLC) to identify
      the cause of prolonged neuromuscular blockade in a child who had received 2 mg.kg
      1 of succinylcholine. Upon analysis by HPLC the syringe was found to contain
      succinylcholine (10 mg.ml-1) and also atracurium (5 mg.ml-1), so that a diagnosis
      was established. In situations where medication errors are suspected, we
      recommend saving syringe contents for analysis for confirmation of the agent.

PMID- 1989728
TI  - Anaesthesia training and development in Nepal 1985-1990.
AB  - In 1985 a diploma program in anaesthesia was established in Kathmandu, Nepal, as
      a joint venture between the Institute of Medicine in Kathmandu and the University
      of Calgary. Development of the program and of the specialty in the capital city
      of Kathmandu was continuously documented during the next five years by local and
      visiting faculty. In 1990 teams of two Nepali and one Canadian anaesthetist also
      conducted a survey of each of the seven 50-100 bed zonal hospitals which did not
      previously have a trained anaesthetist and which are now staffed by graduates of
      the diploma program. In 1985 Nepal, with a population of 16 million, had seven
      trained Nepali anaesthetists all of whom worked in two hospitals in Kathmandu. By
      the end of 1989, 19 physicians had graduated. Seven of these continue to work in
      Kathmandu hospitals, nine work in zonal hospitals throughout the country and two
      are taking higher anaesthesia training in the United Kingdom. Additional Nepali
      anaesthetists have returned from training abroad, and the Society of
      Anaesthesiologists of Nepal, which joined the World Federation of Societies of
      Anaesthesiologists in 1988, now has 34 members. An annual anaesthesiology
      symposium is held, and weekly clinical meetings are organized in the major
      hospitals in Kathmandu. Anaesthetists who work in the zonal hospitals have
      limited supplies of drugs and equipment and opportunities for continuing medical
      education are virtually nonexistent.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1989730
TI  - Salvaging inadequate epidural anaesthetics: "the chloro-procaine save".

PMID- 1989729
TI  - H1 and H2 receptor antagonists and hepatic oxygen supply-demand relationship in
      pigs.
AB  - The hypothesis that histamine receptor (H1 and H2) blockade beneficially affects
      the hepatic oxygen supply-demand relationship was tested during experiments
      performed on 13 miniature pigs. Hepatic arterial and portal blood flows were
      measured with electromagnetic flowmeters. Cardiac output was determined by
      thermodilution. H1 and H2 receptor blockade was achieved with promethazine, 5
      mg.kg-1 and cimetidine 30 mg.kg-1 IV, respectively. The study demonstrated no
      significant effect of H1 and H2 receptor blockade on hepatic oxygen uptake and no
      noticeable effects of cimetidine on hepatic circulation. However, promethazine
      decreased total hepatic blood flow, primarily by decreasing portal blood flow;
      this resulted in an increase in oxygen extraction as reflected in a decreased
      oxygen content in hepatic venous blood. The results reject the posed hypothesis:
      H1 receptor antagonist promethazine decreased, while H2 receptor antagonist
      cimetidine did not affect hepatic blood flow and oxygen supply; hepatic oxygen
      demand remained unaffected during H1 and H2 receptor blockade.

PMID- 1989731
TI  - Propofol bradycardia.

PMID- 1989732
TI  - Intra-arterial verapamil to reverse acute ischaemia of the hand after radial
      artery cannulation.

PMID- 1989733
TI  - Pulmonary oedema associated with airway obstruction.

PMID- 1989734
TI  - Laryngeal mask airway and visualisation of vocal cords during thyroid surgery.

PMID- 1989735
TI  - Cardiac sympathetic tone in anaesthetized diabetics.
AB  - To assess cardiac sympathetic nervous function in diabetics, the heart rates
      attained following a pharmacological dose of intravenous atropine, 23
      micrograms.kg-1, were studied under N2O, isoflurane anaesthesia in diabetics (n =
      21) and nondiabetics (n = 30). Atropine-induced heart rate in diabetics was
      significantly lower than that in nondiabetics (95 +/- 14 (SD) bpm vs 109 +/- 12
      bpm, P less than 0.001) and were closely related to preoperative orthostatic
      diastolic blood pressure change (r = 0.60, P less than 0.01). There was some
      correlation between the atropine-induced heart rate and preoperative RR-variation
      in diabetics (r = 0.50, P less than 0.05). The findings suggest that cardiac
      sympathetic function may also be impaired in diabetics with orthostatic
      hypotension.

PMID- 1989736
TI  - Post-caesarean section analgesia: a comparison of epidural butorphanol and
      morphine.
AB  - Epidural butorphanol 1, 2 and 4 mg were compared with morphine, 5 mg, for
      postoperative analgesia in 92 consenting, healthy, term parturients who had
      undergone Caesarean section under epidural lidocaine anaesthesia in a randomized
      double-blind study. Postoperative pain was assessed using a visual analogue scale
      and recorded with heart rate, blood pressure and respiratory rate. The
      demographic characteristics, and the incidences of primary and repeat Caesarean
      sections, were not different among the four treatment groups. At 15, 30, 45 and
      60 min after treatment the median pain scores following butorphanol were similar
      and lower than those following morphine (P less than 0.05). Calculated median
      percentage pain relief values for butorphanol were higher than morphine at each
      of these times (P less than 0.05). At 90 min and 2 hr the pain scores and pain
      relief values were similar. Beyond 45 min the number of patients requesting
      supplemental medication and dropping out of the study increased progressively in
      both the butorphanol and morphine treated patients. The attrition profiles for
      butorphanol were different from morphine (P less than 0.01). The median time in
      the study was greater than 24 hr for morphine, and 3, 2.5 and 4 hr for
      butorphanol, 1, 2 or 4 mg, respectively. No patient developed a clinically
      important change in heart rate or blood pressure, and none experienced a decrease
      in respiratory rate below 12 breaths.min-1. One of 69 patients (1.4 per cent) who
      received butorphanol developed pruritus compared with ten (43 per cent) of 23
      patients who received morphine. The global assessments of the adequacy of
      analgesia were indistinguishable between morphine and butorphanol. Epidural
      butorphanol provides safe, effective postoperative analgesia, has a prompt onset,
      and a limited duration.

PMID- 1989737
TI  - Disposition of propofol infusions for caesarean section.
AB  - The disposition of propofol was studied in women undergoing elective Caesarean
      section. Indices of maternal recovery and neonatal assessment were correlated
      with venous concentrations of propofol. After induction of anaesthesia with
      propofol 2.0 mg.kg-1, ten patients received propofol 6 mg.kg-1.hr-1 with nitrous
      oxide 50 per cent in oxygen (low group) and nine were given propofol 9 mg.kg-1.hr
      1 with oxygen 100 per cent (high group). Pharmacokinetic variables were similar
      between the groups. The mean +/- SD Vss = 2.38 +/- 1.16 L.kg-1, Cl = 39.2 +/-
      9.75 ml.min-1.kg-1 and t1/2 beta = 126 +/- 68.7 min. At the time of delivery (8
      16 min), the concentration of propofol ranged from 1.91-3.82 micrograms.ml-1 in
      the maternal vein (MV), 1.00-2.00 micrograms.ml-1 in the umbilical vein (UV) and
      0.53-1.66 micrograms.ml-1 in the umbilical artery (UA). Neonates with high UV
      concentrations of propofol at delivery had lower neurologic and adaptive capacity
      scores 15 minutes later. The concentrations of propofol were similar between
      groups during the infusion but they declined at a faster rate in the low group
      postoperatively. Maternal recovery times did not depend on the total dose of
      propofol but the concentration of propofol at the time of eye opening was greater
      in the high group than the low group (1.74 +/- 0.51 vs 1.24 +/- 0.32
      micrograms.ml-1, P less than 0.01). The rapid placental transfer of propofol
      during Caesarean section requires propofol infusions to be given cautiously,
      especially when induction to delivery times are long.

PMID- 1989738
TI  - Serum gastrin and blood glucose levels during halothane-nitrous oxide anaesthesia
      and strabismus surgery in children.
AB  - The purpose of this study was to determine whether serum gastrin levels are
      increased by reflexogenic stimuli applied to the extrinsic muscles of the eye.
      Serum gastrin and blood glucose concentrations were measured in ten normal
      children aged between 5 and 12 yr during general anaesthesia with halothane and
      nitrous oxide and during strabismus surgery. Fasting basal concentrations of
      gastrin (33.6 +/- 14.8 pg.ml-1) and of glucose (4.43 +/- 0.72 mmol.L-1) were in
      the normal range of values for children. Intravenous atropine (0.01 mg.kg-1),
      general anaesthesia with halothane in nitrous oxide and oxygen by mask for three
      minutes, tracheal intubation, extraocular muscle stimulation and surgical stress
      did not cause any variation in the mean serum gastrin concentration. On the
      contrary, tracheal intubation and surgical stress increased blood glucose
      concentrations (P less than 0.05). There was no difference in the serum gastrin
      levels after extraocular muscle stimulation between children with positive or
      negative oculocardiac reflexes (44.5 +/- 16.7 pg.ml-1 vs 38 +/- 14.7 pg.ml-1,
      respectively). The incidence of vomiting predischarge was 60 per cent. Serum
      gastrin levels did not differ between children who vomited and children who did
      not (44.3 +/- 18.5 pg.ml-1 vs 47.1 +/- 16.9 pg.ml-1, respectively). Vomiting
      after strabismus surgery cannot be attributed to high gastrin serum levels.
      Consequently, it is unlikely that vomiting after strabismus surgery is linked to
      an "oculogastric reflex" with the vagus nerve as the efferent pathway.

PMID- 1989739
TI  - An alternative oxygen delivery system for infants and children in the post
      anaesthesia care unit.
AB  - This randomized controlled trial compared the compliance of a blow-by oxygen
      method with the standard face mask by children recovering from anaesthesia. The
      rate at which a face mask was rejected when applied to infants and children in
      PACU was compared with that of a proposed "hose" method. The efficacy of the
      "hose" as a method of oxygen supplementation in children at low and high risk for
      developing postoperative hypoxaemia was also compared with the face mask. Using a
      Nellcor N-200 pulse oximeter, 66 infants and children (mean age 2.3 yr, range 2
      mo-6 yr) were continuously monitored for 30 min upon arrival in the PACU.
      Patients were randomized to receive oxygen supplementation with either the face
      mask or the proposed "hose" method. The results showed a greater than 80 per cent
      rejection of the face mask in contrast to 100 per cent compliance with the "hose"
      method. The SaO2 measurements following 5, 15 and 30 min of O2 supplementation
      with the hose were all significantly higher than the SaO2 measurements obtained
      on room air upon arrival to the PACU. Patients with pre-existing cardiopulmonary
      disease had a 20 per cent incidence of arterial oxygen desaturation upon arrival
      to the PACU versus 2.1 per cent of patients with no pre-existing disease. It is
      concluded that the "hose" is associated with high patient compliance and is
      effective in the PACU in increasing the SaO2 in children at low or high risk of
      developing postoperative hypoxaemia.

PMID- 1989740
TI  - Antiemetic prophylaxis with promethazine or droperidol in paediatric outpatient
      strabismus surgery.
AB  - This randomized, double-blind study evaluated the antiemetic efficacy and the
      side-effects of promethazine pretreatment (0.5 mg.kg-1 IV + 0.5 mg.kg-1 IM)
      versus droperidol + placebo pretreatment (droperidol, 0.075 mg.kg-1 IV +
      physiological saline, 0.02 ml.kg-1 IM). One hundred unpremedicated ASA physical
      status I children ranging from two to ten years, and undergoing outpatient
      strabismus surgery were studied. All children received inhalational anaesthesia
      with halothane, nitrous oxide and oxygen. Neither opioids nor muscle relaxants
      were used. The incidence of vomiting and/or retching and the incidence of side
      effects were determined in the post-anaesthesia recovery room (PARR), in the
      short-stay surgical unit (SSSU), and after discharge from the hospital (including
      the journey and the stay at home during the first postoperative day).
      Promethazine and droperidol were equally effective in reducing the incidence of
      vomiting before discharge to two and eight per cent respectively. On the
      contrary, the incidence of vomiting after discharge and overall were
      significantly less with promethazine (ten and ten per cent) than with droperidol
      pretreatment (54 and 56 per cent) (P less than 0.0001). Promethazine permitted
      the time to discharge from the hospital to be reduced to an average of three
      hours, without increasing the incidence of vomiting postdischarge. Promethazine
      pretreatment is much less expensive than droperidol pretreatment. The incidence
      of restlessness was significantly less with droperidol (eight per cent) than with
      promethazine (36 per cent) (P less than 0.001). Promethazine pretreatment demands
      the use of an analgesic like acetaminophen in order to reduce the incidence of
      postoperative pain and restlessness.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1989741
TI  - Alfentanil pharmacokinetics in patients undergoing abdominal aortic surgery.
AB  - The pharmacokinetics of alfentanil, 300 micrograms.kg-1 IV, were determined in
      patients undergoing elective abdominal aortic reconstruction. The mean age (+/-
      SD) of the patients was 64.3 +/- 7.4 yr; their mean weight was 74.7 +/- 13.8 kg.
      Five patients underwent aneurysm repair and six had aortobifemoral grafting.
      Serum alfentanil concentrations were measured by gas-liquid chromatography in
      samples drawn at increasing intervals over a 24-hr period. A three-compartment
      model was fitted to the concentration versus time data. The volume of the central
      compartment and the volume of distribution at steady state (Vdss) were 0.44 +/-
      0.022 and 0.63 +/- 0.32 L.kg-1, respectively. Total drug clearance was 6.4 = 1.9
      ml.min-1.kg-1. The elimination half-time was 3.7 +/- 2.6 hr. Patient age was
      positively correlated with both Vdss and elimination half-time. There were no
      significant correlations between the pharmacokinetic variables and the duration
      of aortic cross-clamping, the duration of surgery, or the rate or total volume of
      IV fluids infused intraoperatively. In general surgical patients, the elimination
      half-time of alfentanil has been reported to be 1.2-2.0 hr. Although the
      elimination half-time of alfentanil was longer in patients undergoing abdominal
      aortic surgery, alfentanil was eliminated much faster than either fentanyl or
      sufentanil in this patient population.

PMID- 1989742
TI  - [Comparison of the incidence of bleeding of 2 anesthetic technics midazolam
      alfentanil versus propofol-alfentanil during treatment of otospongiosis].
AB  - This study was performed to compare the incidence of bleeding associated with two
      anaesthetic techniques during otolaryngological microsurgery. Twenty-eight venous
      interpositions for otospongiosis have been carried out at random either under
      local anaesthesia combined with light sedation (midazolam 0.1 mg.kg-1 and
      alfentanil 0 micrograms.kg-1) or using general anaesthesia (propofol 2.5 mg.kg-1,
      then 9 mg.kg-1.hr-1 and alfentanil 30 micrograms.kg-1, then 15 micrograms.kg-1).
      The patients' lungs were mechanically ventilated. Every ten minutes, heart rate,
      arterial blood pressure and FETCO2 were observed. Bleeding was assessed on a four
      point scale and evaluated according to its duration and the annoyance that it
      caused. General anaesthesia was clinically better tolerated. Heart rate and
      arterial blood pressure were lower than with general anaesthesia. The end
      expiratory CO2 was 4.7 +/- 0.2 per cent. Bleeding was less frequent, lasted less
      time, but when it occurred the surgical disturbance was identical in the two
      groups. General anaesthesia produced a less bloody operating field and local
      anaesthesia required the cooperation of the patient.

PMID- 1989743
TI  - Interpleural analgesia improves pulmonary function after cholecystectomy.
AB  - The purpose of this study was to examine the effects of interpleural bupivacaine
      on analgesia and ventilatory capacity after cholecystectomy. Forty-two patients
      undergoing elective cholecystectomy were randomly assigned to two groups: one to
      receive interpleural administration of bupivacaine-adrenaline mixture (Group 1 =
      22 patients) and the other standard administration of intramuscular meperidine
      (Group 2 = 20 patients) for postoperative pain relief. The intensity of pain was
      evaluated by a visual analogue scale (VAS) preoperatively as well as at 2, 8, 24
      and 48 hr postoperatively. At the same time, FVC and FEV1.0 measurements were
      obtained for all patients. The group given interpleural bupivacaine had better
      pain relief with mean VAS of 0.6 +/- 0.9 (mean +/- SD) 1.1 +/- 1.4, 0.6 +/- 0.9
      and 0.8 +/- 1.2 compared with 5.2 +/- 2.2, 5.8 +/- 2.7, 5.5 +/- 2.2 and 4.5 +/-
      1.8 for patients receiving meperidine (P less than 0.001). The patients in Group
      1 also had larger FVC and FEV than those in Group 2: FVC 22 +/- 14.5 per cent vs
      32 +/- 15.2 per cent (P less than 0.005), FEV1.0 25 +/- 15.5 vs 38 +/- 14.8 per
      cent (P less than 0.001) (mean +/- SD). We conclude that the interpleural
      analgesia can achieve better pain relief with greater ventilatory capacity than a
      standard analgesic regimen in the first two days after cholecystectomy.

PMID- 1989745
TI  - The TURP syndrome.
AB  - This article discusses the presentation, aetiology, treatment and prevention of
      central nervous system disturbances after transurethral resection of the
      prostate. Nausea and vomiting, visual symptoms, and altered states of
      consciousness have been reported as complications due to intravascular absorption
      of irrigating fluid. Hypotonicity after absorption of the irrigating fluid causes
      cerebral oedema. Hyperglycinaemia may cause visual disturbances and
      hyperammonaemia may cause delayed coma.

PMID- 1989747
TI  - Readers' guide to critical care guidelines.

PMID- 1989746
TI  - Transoesophageal echocardiogram may fail to diagnose perioperative myocardial
      infarction.
AB  - We report a case in which a 55-yr-old man undergoing aortocoronary bypass was
      monitored with electrocardiogram and transoesophageal echocardiogram.
      Intraoperative electrocardiogram and simultaneous ECG recordings using the Holter
      monitor showed an ST elevation of greater than 2 mm and new Q wave formation in
      leads AVF and V5 during skin closure. However, the transoesophageal
      echocardiogram showed no wall motion abnormalities. No significant haemodynamic
      abnormalities were observed during the period of intraoperative ECG changes. He
      was treated with nitroglycerin infusion. Confirmation of a perioperative
      myocardial infarct was documented by postoperative 12-lead ECG and CPK-MB. A post
      operative transthoracic echocardiogram showed a hypokinetic left ventricle with
      an anteroapical infarct. Thus transoesophageal echocardiography failed to detect
      an apical wall motion abnormality when the probe was placed at the midpapillary
      level. This limitation can be overcome by periodically obtaining apical views or
      by using probes with more than one imaging plane.

PMID- 1989744
TI  - Calcium-channel blockers and anaesthesia.
AB  - Verapamil was the first calcium-channel blocker (CCB). It has been used since
      1962 in Europe then in Japan for its antiarrhythmic and coronary vasodilator
      effects. The CCB have become prominent cardiovascular drugs during the last 15
      years. Many experimental and clinical studies have defined their mechanism of
      action, the effects of new drugs in this therapeutic class, and their indications
      and interactions with other drugs. Due to the large number of patients treated
      with CCB it is important for the anaesthetist to know the general and specific
      problems involved during the perioperative period, the interactions with
      anaesthetics and the practical use of these drugs.

PMID- 1989748
TI  - Guidelines for care: the time has come.

PMID- 1989749
TI  - Are we ready to regionalize pediatric intensive care?

PMID- 1989750
TI  - Should measurements of tissue pH and PO2 be included in the routine monitoring of
      intensive care unit patients?

PMID- 1989751
TI  - Use of vasoactive drugs to support oxygen transport in sepsis.

PMID- 1989752
TI  - Defining the hypoxic threshold.

PMID- 1989753
TI  - Use of the Pediatric Risk of Mortality score to predict nosocomial infection in a
      pediatric intensive care unit.
AB  - OBJECTIVE: To define infection rates in patients with Pediatric Risk of Mortality
      (PRISM) scores greater than and less than 10 on admission to the pediatric ICU
      (PICU). DESIGN: Descriptive. SETTING: An 18-bed PICU admitting patients of all
      ages except nonsurgical neonates; within a 585-bed tertiary care pediatric
      hospital. PATIENTS: Patients admitted to the PICU from July 1987 to February 1988
      inclusive. Of 685 admitted, 480 were followed for greater than or equal to 72 hr.
      METHODS: The baseline state of the patients on admission was determined by a
      designated intensivist using the PRISM score. Other variables included age,
      length of stay, and hospital day of onset of infection. Infections were
      identified by a designated intensivist who undertook prospective daily bedside
      observation, chart, radiographic, and laboratory review. MEASUREMENTS AND MAIN
      RESULTS: Equal portions of patients had PRISM scores less than and greater than
      10. Significantly more infections occurred in the high PRISM population (10.8%
      vs. 3.4%, p less than .001). This association held through age, service, and
      length of stay. Sensitivity, specificity, positive and negative predictive values
      of a PRISM score greater than 10 were 75%, 53%, 11%, and 97%, respectively.
      Bacteremias accounted for 36% of infections, skin/eye/drain site 22%, respiratory
      16%, wound 15%, and urine 9%. The most prevalent organisms were coagulase
      negative staphylococci (32%), Pseudomonas aeruginosa (23%), Candida sp. (20%),
      and S. aureus (9%). CONCLUSIONS: A PRISM score greater than 10 on PICU admission
      characterizes a population within the PICU at increased risk of infection.
      However, 93% of patients did not develop infection and thus, a negative
      predictive value of 97% yields little additional information.

PMID- 1989754
TI  - Reliability of the bronchoscopic protected catheter brush in the diagnosis of
      pneumonia in mechanically ventilated patients.
AB  - OBJECTIVE: To assess the usefulness of the telescoping plugged catheter in the
      diagnosis of nosocomial pneumonia. DESIGN: Prospective study. PATIENTS: A total
      of 103 ventilated patients with suspected pneumonia were prospectively studied
      over 20 months. RESULTS: The quantitative cultures of the protected brush
      specimen detected pulmonary bacterial infection (greater than 10(3) cfu/mL) in 49
      (47.5%) patients. Subsequent follow-up confirmed pneumonia in 41 patients; in
      only one patient was a positive protected brush specimen culture established as a
      false-positive result. There were 54 patients with less than 10(3) cfu/mL and the
      diagnosis was excluded in 36 of them. We identified eight patients with false
      negative protected brush specimen cultures. The results obtained by this
      technique allowed us to modify treatment in 49 (47.5%) patients. CONCLUSIONS: The
      telescoping plugged catheter demonstrated significant bacterial infection in a
      relatively small proportion of patients in whom bacterial lung infection was
      suspected. This technique can be safely performed and is a sensitive and specific
      method to establish the cause of pneumonia, thus allowing specific treatment and
      the avoidance of inappropriate antibiotic therapy.

PMID- 1989755
TI  - Ineffectiveness of dantrolene sodium in the treatment of heatstroke.
AB  - STUDY OBJECTIVE: To determine the efficacy of dantrolene sodium in the treatment
      of heatstroke. DESIGN: Randomized, double-blind, placebo-controlled trial.
      SETTING: Heatstroke center in Makkah, Saudi Arabia. PATIENTS: Fifty-two adult
      patients with heatstroke. INTERVENTIONS: Patients were assigned to receive either
      dantrolene sodium (2 mg/kg body weight iv) or placebo. Conventional cooling
      therapy was initiated in all. MEASUREMENTS AND MAIN RESULTS: There was no
      significant difference in the mean cooling times for the treatment and control
      groups (67.9 vs. 69 min). There was only one death in the control group.
      Complications were seen in six (23%) patients receiving dantrolene sodium and
      seven (27%) patients receiving placebo; the difference was not statistically
      significant. There was no significant difference in the mean number of hospital
      days (4.7 +/- 2.0 vs. 2.9 +/- 0.9 days). CONCLUSION: Treatment with dantrolene
      sodium at the dose used, did not prove beneficial to patients with heatstroke.

PMID- 1989756
TI  - High incidence of cardiopulmonary complications associated with implantation of
      adrenal medullary tissue into the caudate nucleus in patients with advanced
      neurologic disease.
AB  - OBJECTIVE: The purpose of our study was to examine the cardiopulmonary
      complications of a group of patients who had undergone implantation of adrenal
      medullary tissue into the caudate nucleus for treatment of neurologic disease.
      DESIGN: Prospective study with partially matched historical controls. SETTING:
      Tertiary care community medical center. PATIENTS AND METHODS: Seven patients with
      advanced Parkinson's disease and three patients with progressive supranuclear
      palsy underwent implantation of adrenal medullary tissue into the caudate
      nucleus. These patients were compared with respect to their cardiopulmonary
      complications with a control group who had undergone craniotomy and then compared
      with a control group who had undergone only abdominal surgery. RESULTS: In the
      study group, six patients developed major postoperative complications including
      development of large pleural effusions, lobar atelectasis, pneumonia, upper
      airway obstruction, and cardiac arrest. Three patients had minor complications
      including development of small pleural effusions, subsegmental atelectasis,
      purulent bronchitis, mild congestive heart failure, and atrial
      flutter/fibrillation. One patient had an unremarkable postoperative course. The
      first control group, whose only surgery was a craniotomy, had only one major
      complication. The second control group, the abdominal surgery control group, had
      one major and five minor complications. CONCLUSION: The particular neurologic
      disease, its severity, and the type of surgery performed appear to be causative
      factors in the high incidence of complications in the study group.

PMID- 1989757
TI  - Mortality prediction models in intensive care: acute physiology and chronic
      health evaluation II and mortality prediction model compared.
AB  - OBJECTIVE: To compare the Acute Physiology and Chronic Health Evaluation (APACHE
      II) score with the Mortality Prediction Model (MPM). DESIGN: A prospective study.
      SETTING: A nine-bed ICU in a 300-bed, nonteaching secondary hospital. PATIENTS:
      Three hundred thirty-two consecutive, unselected adults. MEASUREMENTS AND MAIN
      RESULTS: We found a good correlation between APACHE II and MPM; their performance
      expressed as area under the receiver operating characteristics curve was nearly
      the same. Goodness-of-fit between observed and expected occurrences was better
      for APACHE II than for admission MPM, which overestimated deaths. Because we
      evaluate patients early, often in the Emergency Department, we felt that a "lead
      time bias" could explain this discrepancy. Reevaluation after initial
      stabilization improved the performance of the MPM model to the level of APACHE
      II. CONCLUSIONS: Our investigation indicates that both APACHE II and MPM are good
      predictors of hospital outcome in our population, but the level of intensive care
      services received before conventional ICU admission modifies accuracy of
      predictive models. In any study of outcome using comparative studies of
      classification systems, confounding biases should be measured.

PMID- 1989758
TI  - Cardiac output during liquid (perfluorocarbon) breathing in newborn piglets.
AB  - BACKGROUND AND METHODS: Liquid ventilation using perfluorocarbons is a new
      technique for ventilation of infants with restrictive lung disease. However, this
      method of ventilation has been shown to impair cardiac output (Qt) in several
      animal species, casting doubt as to its feasibility. This study tested whether Qt
      could be maintained during liquid breathing by intravascular volume expansion.
      Seven piglets were carefully hydrated, instrumented for continuous Qt
      measurement, and subjected to 2 hr of liquid breathing. PaCO2 was maintained at
      40 to 50 torr (5.3 to 6.7 kPa), and PaO2 greater than 80 torr (greater than 10.7
      kPa). Additional colloid was given during liquid breathing if Qt decreased to
      less than 90% of preliquid breathing values. RESULTS: Four piglets maintained Qt
      throughout the liquid breathing trial with maintenance fluids only. Three piglets
      each required one 10 mL/kg fluid bolus for Qt 82% to 89% of the baseline value,
      after which Qt rapidly increased to greater than 90% of baseline. Oxygen
      consumption and serum lactate levels remained normal throughout liquid breathing.
      CONCLUSION: Qt is readily maintained during liquid breathing in properly hydrated
      animals.

PMID- 1989759
TI  - Oxygen debt and metabolic acidemia as quantitative predictors of mortality and
      the severity of the ischemic insult in hemorrhagic shock.
AB  - BACKGROUND AND METHODS: An experimental canine model of hemorrhagic, hypovolemic
      shock is described that uses oxygen debt and its metabolic consequences of lactic
      acidemia and metabolic base deficit as independent variables for the prediction
      of probability of death. RESULTS: Lactic acidemia and metabolic base deficit are
      compared with the conventional hemodynamic variables of BP and cardiac output
      (Qt) as predictors of outcome and are shown to be superior using a modified
      Kaplan-Meier probability statistic. The LD50 for oxygen debt is shown to be 113.5
      mL/kg, 12.9 mmol/L for lactate, and -18.8 mmol/L for base excess (BE). Comparison
      is made between the ability of Qt, BP, shed blood, BE, and lactate to predict
      oxygen debt. CONCLUSIONS: Of the single-variable predictors, BE shows the highest
      explained variability. However, a combined prediction from both lactate and BE
      appears superior to the use of either alone. Using this regression to compute the
      oxygen debt, it is possible to estimate accurately the actual level of oxygen
      debt from the BE and lactate values obtained during hemorrhagic hypovolemia. From
      serial determinations over time of the increase in these biochemical variables
      above the oxygen debt baseline, it is possible to estimate the rate of oxygen
      debt accumulation and the time remaining until the LD50 will be reached as
      indicators of the severity of the total body ischemia resulting from hemorrhagic
      shock.

PMID- 1989760
TI  - Inhibition by methylprednisolone of leukocyte-induced pulmonary damage.
AB  - BACKGROUND AND METHODS: The purpose of this study was twofold: the development of
      a chronic model of leukocyte-mediated pulmonary injury and the evaluation of the
      protective effects of methylprednisolone. Rabbits were inoculated ip with
      zymosan. Blood gases and circulating leukocytes were evaluated. Survivors were
      killed on day 10 for microscopic studies and for the evaluation of lung lipid
      peroxidation through the by-product malondialdehyde. RESULTS: Intraperitoneal
      zymosan resulted in a marked decrease of Pao2 and circulating leukocytes, and
      increased cellularity of alveolar septa, interstitial edema, and increased lung
      malondialdehyde. Pulmonary damage was partially prevented when methylprednisolone
      was administered before zymosan inoculation, but not when methylprednisolone was
      given 24 hr later. CONCLUSIONS: The authors conclude that a local nonseptic
      inflammatory stimulus may provoke remote changes to the lungs and that
      methylprednisolone may counteract the process only if it is administered before
      or very early after the onset of inflammation.

PMID- 1989761
TI  - Optimizing fresh gas flow and circuit design for the delivery of continuous
      positive airway pressure.
AB  - OBJECTIVE: To examine the effect of varying circuit design and the fresh gas flow
      rate on the circuit work imposed by a continuous positive airway pressure (CPAP)
      circuit. DESIGN: Circuit work was measured during simulated inspiration (500 mL)
      with a lung model at inspiratory flow rates (V) of 40, 60, and 80 L/min during
      the administration of 10 cm H2O CPAP through either a modified Mapleson-A or
      modified Mapleson-D circuit, both alone and when connected to a face mask (i.e.,
      simulating an intubated and nonintubated patient). Fresh gas flow was varied from
      10 to 250 L/min. RESULTS: The minimum circuit work occurred at a fresh gas flow
      rate approximating V; however, circuit work was consistently lower for the
      modified Mapleson-A circuit compared with the modified Mapleson-D circuit. As the
      fresh gas flow rate was increased sequentially to 250 L/min, circuit work
      remained close to the minimum value for the modified Mapleson-A, but increased
      gradually with the modified Mapleson-D, e.g., from 0.017 kg.m/L at a fresh gas
      flow rate and V of 80 L/min to 0.035 kg.m/L at a fresh gas flow rate of 250 L/min
      and a V of 80 L/min. Rotation of the fresh gas flow inlet did not change the
      circuit work vs. fresh gas flow rate relationship. Addition of a face mask
      resulted in a smaller increase in circuit work for the modified Mapleson-D with
      increasing fresh gas flow rate. However, unlike the modified Mapleson-A circuit
      alone, the addition of a mask caused circuit work to increase with increasing
      fresh gas flow rate. CONCLUSIONS: The modified Mapleson-A circuit at a fresh gas
      flow rate equal to V minimizes circuit work, and hence represents an optimal CPAP
      circuit. The increases in circuit work at fresh gas flow rates above V that were
      found with the modified Mapleson-D circuit are not due to inertial differences,
      and are likely due to turbulent gas flow.

PMID- 1989762
TI  - Gastric tonometry in healthy volunteers: effect of ranitidine on calculated
      intramural pH.
AB  - OBJECTIVE: To determine if intraluminal production of CO2 leads to
      underestimation of gastric intramural pH (pHi) by tonometry. DESIGN:
      Nonrandomized controlled study. PATIENTS: Healthy volunteers. INTERVENTIONS: NG
      tonometers were placed in healthy volunteers. Some of the volunteers (n = 11)
      were pretreated with ranitidine to prevent secretion of protons into the gastric
      lumen. Others (n = 13) were untreated (i.e., gastric acid secretion was
      uninhibited). MEASUREMENTS AND MAIN RESULTS: Gastric pHi was calculated from the
      arterial (HCO3-) and the tonometrically determined intraluminal PCO2 using the
      Henderson-Hasselbalch equation. Intraluminal PCO2 was significantly higher in the
      control group (54 +/- 14 torr [7.2 +/- 1.9 kPa]) than in the ranitidine-treated
      group (42 +/- 4 torr [5.6 +/- 0.4 kPa], p = .02). Mean gastric luminal pH was 1.9
      +/- 0.6 in the control group as compared with 6.7 +/- 0.7 in volunteers treated
      with ranitidine (p less than .01). Mean calculated gastric pHi was 7.30 +/- 0.11
      in the untreated group and 7.39 +/- 0.03 in the ranitidine-treated group (p less
      than .03). CONCLUSIONS: These data suggest that intraluminal production of CO2
      from the titration of gastric HCO3- by secreted H+ can result in the
      underestimation of gastric pHi by tonometry. This phenomenon can be eliminated by
      H2-receptor blockade.

PMID- 1989763
TI  - Guidelines for standards of care for patients with acute respiratory failure on
      mechanical ventilatory support. Task Force on Guidelines; Society of Critical
      Care Medicine.

PMID- 1989764
TI  - Guidelines for categorization of services for the critically ill patient. Task
      Force on Guidelines; Society of Critical Care Medicine.

PMID- 1989765
TI  - Heart-lung transplantation for adult respiratory distress syndrome.

PMID- 1989766
TI  - Use of plasmapheresis in acute theophylline toxicity.

PMID- 1989767
TI  - Arsenic-induced torsade de pointes.

PMID- 1989768
TI  - Cardiac arrest secondary to emotional stress and torsade de pointes in a patient
      with associated magnesium and potassium deficiency.

PMID- 1989769
TI  - Efficiency of a continuous infusion of propofol in a patient with tetanus.

PMID- 1989770
TI  - Successful treatment of adult respiratory distress syndrome with oral ibuprofen.

PMID- 1989771
TI  - Severity of disease classification system.

PMID- 1989772
TI  - Normal ventilation-perfusion lung scan in a patient with proven pulmonary
      embolism.

PMID- 1989773
TI  - Axillary vein cannulation in neonates.

PMID- 1989774
TI  - New method to prevent epidural catheter adapter disconnection.

PMID- 1989775
TI  - Intraoperative cardiac arrest in a young woman undergoing liposuction.

PMID- 1989776
TI  - Deleterious effect of prolonged sodium administration and fluid restriction after
      partial correction of severe hyponatremia.

PMID- 1989777
TI  - Chronic lower-extremity ischemia. Part I.

PMID- 1989778
TI  - Pulmonary function as a phenotype physiologic marker of cardiovascular morbidity
      and mortality.

PMID- 1989779
TI  - Tuberculosis treatment. Risk, benefit and perspective.

PMID- 1989780
TI  - Clinical applications of soluble interleukin-2 receptor in granulomatous disease.

PMID- 1989781
TI  - Long-term postthoracotomy pain.
AB  - We used a pain questionnaire to evaluate the prevalence and functional
      significance of long-term postthoracotomy pain. Data on 56 patients who were at
      least 2 months postsurgery were analyzed. Thirty patients (54 percent) with a
      median follow-up of 19.5 months had persistent pain; 26 others were pain free at
      a median of 30.5 months postthoracotomy. Pain was reported in 24 of 44 patients
      (55 percent) who were more than one year after surgery, 13 of 29 patients (45
      percent) more than two years, six of 16 (38 percent) more than three years, and
      three of ten patients (30 percent) greater than four years postthoracotomy. Pain
      intensity was low, but 13 patients stated that pain "slightly" or "moderately"
      interfered with their lives. Five of 56 patients had sufficiently severe chronic
      pain to require either daily analgesic use, nerve blocks, relaxation therapy,
      acupuncture, or referral to a pain clinic. We conclude that long-term chest wall
      pain is common postthoracotomy. It is generally not severe, but a small
      proportion of patients may experience persistent, moderately disabling pain.

PMID- 1989782
TI  - Use of a biotinylated DNA probe specific for the human Y chromosome in the
      evaluation of the allograft lung.
AB  - A cloned 3.4 kilobase DNA probe derived from the heterochromatin of the Y
      chromosome was used to investigate the regeneration and reepithelialization of
      allograft lungs of nine recipients who received sex mismatched donor organs.
      Patients were monitored for varying periods of time, up to four years, by
      transbronchial biopsy. In situ hybridization on paraffin-embedded biopsies
      utilizing the Y probe revealed that bronchial and alveolar epithelium and
      arterial and venous endothelium of the peripheral lung retained a donor
      phenotype, irrespective of episodes of acute or chronic rejection (obliterative
      bronchiolitis) which are known to injure these cellular subsets. In contrast,
      migratory cells, lymphocytes and macrophages, gradually, at varying rates,
      infiltrated the allografted lungs, replacing preexisting donor elements. Cases of
      active OB were manifested by infiltration of bronchioles by sex-mismatched
      lymphocytes; however, in some instances, quiescent recipient lymphocytes
      colonized the allograft and were unassociated with histologic rejection.
      Macrophages of similar sex seemed to cluster together within air spaces. Use of a
      DNA probe for the Y chromosome and in situ hybridization techniques allow
      monitoring of cellular alterations over time in recipients with sex mismatched
      allografts.

PMID- 1989783
TI  - Upper-extremity deep venous thrombosis and pulmonary embolism. A prospective
      study.
AB  - We prospectively evaluated the prevalence of pulmonary embolism (PE) in 30
      consecutive patients with proved deep venous thrombosis (DVT) of the upper
      extremity. Ten patients (seven male and three female; mean age, 43 years) had
      primary DVT, and 20 patients (14 male and six female; mean age, 52 years) had
      catheter-related DVT. Ventilation-perfusion lung scans were routinely performed
      at the time of hospital admission to all but one patient (one patient was
      critically ill, and he died four days after DVT diagnosis because of massive PE).
      Lung scan findings were normal in nine of ten patients with primary DVT, and they
      were indetermine in the remaining patient. By contrast, perfusion defects were
      considered highly suggestive of PE in four patients with catheter-related DVT;
      two patients had indeterminate lung scans, and 13 patients had normal scans. We
      conclude that PE is not a rare complication in upper extremity DVT, and that
      patients with catheter-related DVT seem to be at a higher risk.

PMID- 1989784
TI  - Deep venous thrombosis. Implications after open heart surgery.
AB  - We reviewed the cases of 10,638 cardiac surgical patients to determine the
      incidence of deep vein thrombosis (DVT) after open heart surgery (OHS). Seventy
      seven patients (0.7 percent) had DVT. Group 1 included 36 patients who had DVT
      without pulmonary embolism (PE). Occurrence was equal in either leg.
      Anticoagulation with heparin and warfarin sodium (Coumadin) was employed as
      treatment. Extension of hospital stay was 10.8 days. Group 2 consisted of 41
      patients who experienced PE 9.9 days after OHS. Sixteen patients had known DVT
      and were receiving heparin. In 25 patients, PE was the first event. Risk factors
      for PE included perioperative myocardial infarction (16 percent), atrial
      fibrillation (41 percent); blood type A (70 percent) (p less than 0.05), and
      coronary artery bypass graft (CABG) (98 percent). Twenty-four patients were
      treated with anti-coagulation alone. Six died of recurrent PE; mortality was 25
      percent. Seventeen patients received anticoagulation plus inferior vena cava
      (IVC) interruption using a Hunter balloon. There were no recurrent PEs and there
      was one death from myocardial infarction (6 percent). Deep vein thrombosis and PE
      are rare complications of OHS. Routine prophylaxis with either heparin or
      warfarin is unnecessary. Patients with DVT, atrial fibrillation (AF), and
      perioperative myocardial infarction are at high risk of PE. Aggressive diagnosis
      to identify major venous thrombi along with anticoagulation and early
      consideration of IVC interruption are recommended for these patients. Patients
      who have undergone OHS and who have PE are at an unusually high risk for
      recurrent PE with death and are more safely treated with IVC interruption and
      anticoagulation than anticoagulation alone.

PMID- 1989785
TI  - Lymphokine-activated killer cell activity in lung cancer.
AB  - This study evaluates local pulmonary immune effector cell lytic activity.
      Purified lymphocyte populations were isolated from BALF obtained from 18 patients
      with bronchogenic carcinoma, six patients with lung disorders other than cancer,
      and ten normal control volunteers matched for age and smoking history. These
      cells were evaluated for NK and LAK cell lytic activity against NK-resistant LAK
      sensitive tumor targets (A549 pulmonary tumor and Daudi tumor cells) and an NK
      sensitive tumor (K562); LAK activity was detected in BALF from 6 of the 18
      patients with cancer. The remaining patients with cancer, the subjects with
      pulmonary disease other than cancer, and the normal volunteers had no detectable
      lytic activity. Peripheral blood lymphocytes from all subjects had only NK lytic
      activity and did not kill the pulmonary tumor target; AMs were not tumoricidal.
      Interleukin-2, which is required for LAK cell activation, was detected only in
      BALF recovered from the six patients with pulmonary LAK lytic activity. These
      results demonstrate that activated LAK cells, capable of killing pulmonary tumor
      cells, are present in BALF of some patients with bronchogenic carcinoma. This
      lytic LAK cell population represents a local pulmonary response against the lung
      cancer in the absence of systemic tumoricidal activity. The functional status of
      pulmonary immune effector cells, as well as the type and quantities of cytokines
      in the lung determine local responsiveness to bronchogenic carcinoma and may well
      control the course of this disease.

PMID- 1989786
TI  - Magnetic resonance imaging in the diagnosis of pulmonary infarction.
AB  - We report for the first time, to our knowledge, MRI features which could
      differentiate noninvasively pulmonary infarction from pneumonia. Three subjects
      with angiographically proven pulmonary infarction showed high T1 weighted MRI
      signals located in the embolic territory. Three patients with pneumonia and one
      patient with emboli, but without infarction, did not have these T1 weighted
      images.

PMID- 1989787
TI  - Soluble interleukin-2 receptor in sera of patients with pulmonary tuberculosis.
AB  - Interleukin-2 receptor, the complex of IL-2R-alpha and/or IL-2R-beta, is
      expressed mainly on T-lymphocytes, and the soluble form of IL-2R-alpha (sIL-2R
      alpha) has been reported to be detected in the serum of patients with
      lymphoproliferative disorders or disease characterized by the cellular immune
      reaction. We measured serum sIL-2R-alpha levels among patients with pulmonary
      diseases and found that sIL-2R-alpha levels were significantly elevated in
      patients with active pulmonary tuberculosis (1,327 +/- 209 U/ml) and sarcoidosis
      (1,037 +/- 115 U/ml) when compared with healthy volunteers (468 +/- 49 U/ml, p
      less than 0.01). Among patients with pulmonary tuberculosis, the sIL-2R-alpha
      levels were high in sera from patients with extensive parenchymal lesions on the
      roentgenogram (2,745 +/- 705 U/ml) and patients with tuberculous pleurisy (2,111
      +/- 679 U/ml). In contrast, the sIL-2R-alpha levels in tuberculous patients with
      minimal lesion (455 +/- 92 U/ml) or moderate lesion (1,082 +/- 189 U/ml) were not
      significantly elevated when compared with healthy volunteers. After the treatment
      with antituberculosis agents, serum sIL-2R-alpha levels decreased in accordance
      with improvement of roentgenographic findings and laboratory data. These results
      suggest that serum sIL-2R-alpha level may be useful as a monitor for the disease
      activity in patients with pulmonary tuberculosis.

PMID- 1989788
TI  - Pulmonary function and cardiovascular risk factor relationships in black and in
      white young men and women. The CARDIA Study.
AB  - Pulmonary function is known to be related inversely to incidence of coronary
      heart disease, congestive heart failure, chronic obstructive lung disease, lung
      cancer, and death from all causes. Reasons for some of these associations are
      poorly understood. Relationships between cardiovascular disease risk factors and
      pulmonary function were examined in 5,115 18- to 30-year-old black and white male
      and female participants in the study of Coronary Artery Risk Development in Young
      Adults (CARDIA). Forced expiratory volume in 1 s adjusted for height (FEV1/Ht2)
      was significantly lower in smokers than nonsmokers and in persons who reported
      shortness of breath; FEV1/Ht2 was correlated positively with a history of
      strenuous physical activity, duration of exercise on the treadmill, and high
      density lipoprotein cholesterol. It was associated negatively with skinfold
      thicknesses, serum triglycerides, fasting serum insulin, and the Cook Medley
      scale of hostility. The association between pulmonary function and heart disease
      risk may reflect associations with physical fitness, vigor, fatness, and lipid
      profiles, as well as with cigarette smoking.

PMID- 1989789
TI  - Hemodynamic effects of nasal CPAP examined by Doppler echocardiography.
AB  - The effects of incremental application of nasal continuous positive airway
      pressure (0 to 15 cm H2O) on heart rate, pulmonary artery pressure, and cardiac
      index were studied noninvasively by Doppler echocardiography. By two-way analysis
      of variance within two groups (19 normal volunteers and six sleep apnea
      patients), no significant effects on heart rate, pulmonary artery pressure,
      ventricular size, or cardiac index could be found with increasing positive
      intrathoracic pressures and consequent lung hyperinflation. In subjects with
      normal cardiac function, nasal CPAP is safe from a hemodynamic viewpoint. This
      simple, repeatable and noninvasive technique may be used to assess the clinical
      safety and efficacy of prescribed nasal CPAP on cardiac hemodynamics in
      individual patients.

PMID- 1989790
TI  - Pulmonary involvement in the eosinophilia-myalgia syndrome.
AB  - We describe the cases of three women with pulmonary involvement in the
      eosinophilia-myalgia syndrome. The illness was characterized by elevated
      peripheral blood eosinophil counts, myalgias, fatigue, and dyspnea. Two of three
      patients had bilateral infiltrates on chest roentgenograms. All three had
      markedly decreased carbon monoxide diffusing capacities and pulmonary
      hypertension. High-dose prednisone therapy provided only partial resolution of
      the pulmonary symptoms. Open lung biopsy specimens showed chronic interstitial
      and perivascular infiltrates in two of the patients and moderate fibrointimal
      hyperplasia of pulmonary vasculature in the third. High-dose prednisone therapy
      prior to the biopsies may have modified the original histologic features.

PMID- 1989791
TI  - Respiratory muscle strength and control of ventilation in patients with
      neuromuscular disease.
AB  - To assess the relationship between respiratory mechanics and muscle strength and
      control of ventilation in patients with neuromuscular disease (NMD), we compared
      PImax and PEmax at RV, FRC and TLC, total respiratory elastance (Ers) with VT,
      TI, TT, VE, VT/TI, TI/TT, P.01, and P.01/(VT/TI) effective impedance in 21
      patients with NMD and 21 healthy control (C) subjects, in seated position
      breathing room air. Ers in NMD patients was 79 percent higher than in the C
      subjects. While TI, TT, and VT in NMD were approximately half the corresponding C
      values, P.01 was 66 percent greater than in the C subjects (both p less than
      0.001). NMD PImax and PEmax ranged from 37 to 52 percent of corresponding C
      values, respectively. Despite significant respiratory muscle weakness, only 7 of
      16 patients demonstrated a PaCo2 greater than 45 mm Hg. Ventilatory output in NMD
      was modulated by respiratory mechanics as indicated by the increased P.01. In
      spite of muscle weakness, central drive in patients with NMD is not decreased,
      and in fact, is often increased. VE is not an accurate measure of central drive
      because of abnormal intrinsic respiratory mechanics and the effects of conscious
      responses or reflexes.

PMID- 1989792
TI  - Effect of ethanol on the efficacy of nasal continuous positive airway pressure as
      a treatment for obstructive sleep apnea.
AB  - The effect of ethanol ingestion on the efficacy of nasal continuous positive
      airway pressure (nasal CPAP) as a treatment for the obstructive sleep apnea (OSA)
      syndrome was studied in ten obese male subjects undergoing this therapy. On the
      first night of polysomnography, the lowest level of CPAP that maintained airway
      patency was determined (critical level). On the second (control) night (C),
      subjects slept the entire night on this level of CPAP. On the third night (E),
      subjects ingested either 1.5 ml/kg (part A, N = 6) or 2.0 ml/kg (part B, N = 4)
      of 50 percent ethanol (100 proof vodka) over one half-hour starting 1 h before
      bedtime. A serum ethanol level was obtained at bedtime (part A: 63.7 +/- 17.3
      mg/dl; part B: 108.6 +/- 20.6 mg/dl), and subjects were monitored on the critical
      level of CPAP. Comparison of nights C and E for parts A + B showed no difference
      in total sleep time (TST) or the amount of different sleep stages as an absolute
      time or a percentage of TST except that there was more stage 2 (as a percent of
      TST) on E nights. The apnea + hypopnea index and C and E nights did not differ
      and was quite low (3.6 +/- 3.7/h vs 1.9 +/- 2.7/h). Similarly, ethanol ingestion
      did not increase the number of desaturations to at or below 90 and 85 percent, or
      lower the mean arterial oxygen saturation in NREM or REM sleep. Analysis of parts
      A and B separately also showed no differences with respect to the apnea +
      hypopnea index or the number of desaturations on control and ethanol nights. We
      conclude that acute moderate ethanol ingestion does not decrease the efficacy of
      an optimum level of nasal CPAP.

PMID- 1989793
TI  - Comparative study of Legionella pneumophila and other nosocomial-acquired
      pneumonias.
AB  - We studied, in a prospective way, the characteristics of definitively diagnosed
      nosocomially acquired pneumonias in our hospital over 36 months. Out of 55 cases,
      27 were due to Legionella pneumophila and 28 to other, non-Legionella bacteria.
      The cases of legionellosis concentrated in July, August, and December. The only
      risk factors that showed significant differences (p less than 0.05) were general
      anesthesia and surgery and immunosuppressive disease, which were more frequent in
      the non-Legionella group, as were chronic liver disease and lowering of
      consciousness level. The absence of severe underlying disease, chronic or not,
      was uncommon in both groups, but more frequent in the Legionella group. We
      observed no differences in the clinical features of the two groups. Mean values
      of gamma-glutamyltranspeptidase and total bilirubin were higher (p less than
      0.05) in the non-Legionella group. The only x-ray data that showed significant
      difference were pleural effusion, more frequent in the non-Legionella group (p
      less than 0.02). The mortality rate of legionellosis was 14.6 percent compared to
      35.7 percent for the non-Legionella group (p less than 0.05). We conclude that a
      sure differential diagnosis based on clinical, roentgenographic and analytical
      features of both groups is not possible. The relatively low mortality rate of the
      Legionella group, when compared to other series of nosocomial legionellosis,
      could be due to the standard use of erythromycin in the therapeutic approach to
      nosocomial-acquired pneumonia in our hospital.

PMID- 1989794
TI  - The effect of esophageal acid volume on arousals from sleep and acid clearance.
AB  - To assess the effect of different volumes of acid infused into the esophagus,
      seven normal volunteers were studied in the waking and sleep state. All subjects
      were studied for three nights in the sleep laboratory, which included complete
      polysomnographic monitoring and esophageal pH recording. Multiple infusions of
      either 5, 15, or 25 ml of 0.1 N HCL were administered each night. Similar
      infusions were also accomplished in the waking state. The results showed a
      significant (p less than 0.05) decrease in the arousal from sleep with 25-ml vs 5
      ml infusions. During sleep, the latency to the first swallow was significantly (p
      less than .05) shorter with the 25-ml infusion when compared with that of the 5
      ml infusion. While awake, the infusion volume did not affect the latency to the
      first swallow. The acid clearance times were not significantly altered by the
      different volumes infused. It is concluded that the larger volumes of acid in the
      esophagus create an afferent "warning" signal to the central nervous system to
      produce a rapid arousal from sleep along with a shortened interval to the first
      swallow. These responses rapidly empty the larger acid volumes from the
      esophagus.

PMID- 1989795
TI  - An evaluation of the accuracy of Assess and MiniWright peak flowmeters.
AB  - With the advent of small inexpensive peak flowmeters, the at-home monitoring of
      peak flow rates has become an invaluable aid in the treatment of asthmatic
      patients. In this study, we evaluated the performance of the MiniWright and
      Assess peak flowmeters for accuracy and reproducibility. Measurements were made
      at varying peak flow rates and compared with those obtained simultaneously by a
      calibrated pneumotachograph. When this segment of the study was completed, the
      peak flow devices were subjected to 200 uses and were then retested. Four
      MiniWright peak flowmeters that had been extensively used in our clinic were
      tested as well. The Assess peak flowmeter was more accurate than the MiniWright
      at low flow rates (less than 300 L/min), while the MiniWright meter was more
      accurate at high flow rates (greater than 400 L/min). We also found that the
      accuracy of the MiniWright meter deteriorated after 200 uses and worsened further
      after extensive use, while the Assess meter retained its accuracy after 200 uses.

PMID- 1989796
TI  - Amiodarone-induced pulmonary toxicity. Immunoallergologic tests and
      bronchoalveolar lavage phospholipid content.
AB  - Amiodarone (A) is a widely-used antiarrhythmic drug. Pulmonary toxicity is the
      most serious adverse effect with an estimated mortality of 1 to 33 percent. In
      order to determine an element helpful for diagnosis, we examined four patients
      with amiodarone-induced pulmonary toxicity, three patients treated with A,
      without evidence of pulmonary toxicity but with a main underlying pulmonary
      disease, and four healthy volunteers. Daily and cumulative doses or duration of
      treatment were similar in the first two groups. Pulmonary function tests
      (spirometry, CO-diffusing capacity, arterial blood gases), roentgenographic
      examinations, pulmonary biopsies or immunoallergologic tests (skin reaction,
      lymphoblastic transformation test and human basophile degranulation test) did not
      provide any discriminatory element. In APT+, we observed an increased cellularity
      of the bronchoalveolar lavage. Neither the differential cell count nor the
      presence of foamy macrophages were distinguishable between APT+ and APT-. The
      phospholipid composition of BAL fluid showed a decreased total phospholipid and
      phospholipid/protein ratio in all patients compared to normal subjects. These
      changes reflect more the severity of pulmonary disease than the specificity of
      the causative agent. However, we observed that the unique PL which decreases in
      APT- and remains normal in APT+ is phosphatidyl-serine + phosphatidylinositol (PS
      + PI). This has to be confirmed and should be evaluated at different stages of
      the disease to determine an eventual specific element. We conclude that there are
      no data currently available to establish the diagnosis of APT except perhaps for
      the analysis of BAL PL content.

PMID- 1989797
TI  - Utility of bronchoscopic sampling techniques for cryptococcal disease in AIDS.
AB  - Although cryptococcal pneumonia is a well recognized complication of the acquired
      immunodeficiency syndrome, optimal diagnostic approaches remain to be defined.
      During a 32-month period (October 1984 to June 1987), 11 patients were diagnosed
      with CP at our institution. The diagnosis was established in all 11 patients from
      specimens obtained via fiberoptic bronchoscopy (ten) and/or double-lumen catheter
      lavage (one). Direct stains of sedimented bronchoalveolar lavage were positive
      for organisms characteristic of Cryptococcus neoformans in nine of 11 patients.
      Transbronchial biopsies were positive (special histologic stains) in six of eight
      patients; bronchial washings were positive (direct smear) in seven of ten
      patients, the bronchial brushings were positive on stain in six of nine patients,
      and in one patient, a Wang transbronchial needle aspirate was positive on stain.
      Fungal cultures were positive on the BAL in seven of 11 patients, and on the
      bronchial washings in four of ten patients; the TBBx culture samples were all
      negative (zero of three). The serum cryptococcal antigen titer was elevated
      (median = 1:1024) in all eight patients in which it was assayed. Our data suggest
      that BAL and bronchial washings have a combined sensitivity on smear equal to
      that of TBBx and superior to that of TBBx fungal culture. The TBBx does not
      appear to be necessary in this setting. In addition, an elevated serum
      cryptococcal antigen titer appears to be an important adjunct in the evaluation
      of pulmonary infiltrates in AIDS.

PMID- 1989798
TI  - Acute pulmonary embolism triggered by the act of defecation.
AB  - Pulmonary embolism associated with the act of defecation has not been previously
      well described. Recently, we reported our experience with four patients who
      presented to us over a 12-month period with syncope, near syncope, or sudden
      death following the act of defecation. In all four cases, acute pulmonary
      embolism was shown to be the etiology of the defecation-associated events. A
      retrospective chart review of all patients with the diagnosis of pulmonary
      embolism at our institution over a three-year period yielded five additional
      patients with the diagnosis of defecation-associated pulmonary embolism. These
      nine patients accounted for 6.8 percent of all patients with a discharge
      diagnosis of pulmonary embolism seen at our institution during the three-year
      study period. Six of the nine patients died from their defecation-associated
      pulmonary embolism. These six deaths accounted for 25 percent of all deaths from
      pulmonary embolism seen at our institution during the study period. Based on our
      experience, we suggest that the act of defecation may trigger the development of
      acute pulmonary embolism in some patients with deep vein thrombosis.

PMID- 1989799
TI  - Macrophage colony-stimulating factor activity in malignant pleural effusions. Its
      augmentation by intrapleural interleukin-2 infusions.
AB  - The activity of endogenous colony-stimulating factor (CSF) in malignant pleural
      effusions of lung cancer patients before and during daily intrapleural infusions
      of recombinant interleukin-2 (IL-2) was measured quantitatively by colony-forming
      bioassay and radioimmunoassay (RIA). Before therapy, malignant pleural effusions
      had various levels of CSF activities, and this CSF activity was neutralized
      almost completely by anti-M-CSF antibody. RIA also showed that the effusions
      contained various amounts of M-CSF. Daily intrapleural infusion of recombinant IL
      2 caused significant increase in the CSF activities and M-CSF levels in pleural
      effusions. These results indicate that in vivo treatment with IL-2 induces
      production of endogenous M-CSF.

PMID- 1989800
TI  - Ischemia and reperfusion during intermittent coronary occlusion in man. Studies
      of electrocardiographic changes and CPK release.
AB  - The course of 357 balloon inflations performed during 38 angioplasties for single
      vessel coronary artery disease was prospectively studied using continuous ECG
      recording. Ischemic ECG changes appeared during 91 percent of the inflations at a
      mean of 20 +/- 8 seconds after inflation and resolved in 97 percent of those at a
      mean of 11 +/- 5 seconds after deflation. Elevation of the plasma CPK level was
      found in six patients who had ischemic ECG changes for at least 7.8 minutes. The
      duration of ischemia did not exceed 5.4 minutes in any of the patients without
      CPK elevation. Resolution of the ischemic changes was delayed in patients with
      CPK elevation and in last vs initial inflations. We conclude that in patients
      with noninfarcted myocardium, ECG changes follow coronary occlusion and reflow
      very rapidly, detecting these coronary events with a high sensitivity. Lack of
      rapid regression predicts lack of reperfusion, and persistence of ischemia for
      more than 7.8 minutes is sufficient to cause myocardial necrosis.

PMID- 1989801
TI  - Efficacy and safety of intravenous nicardipine in the control of postoperative
      hypertension. IV Nicardipine Study Group.
AB  - In a double-blind, randomized, multicenter study, the efficacy and safety of
      intravenous (IV) nicardipine was compared with placebo in the control of
      postoperative hypertension in cardiac and noncardiac surgical patients. One
      hundred twenty-two patients (17 cardiac and 105 noncardiac surgery) met the entry
      criteria (systolic BP greater than or equal to 140 mm Hg or diastolic BP greater
      than or equal to 95 mm Hg) and were randomized (3:2) to receive IV nicardipine (n
      = 71) or placebo (n = 51). Therapeutic response (greater than or equal to 15
      percent reduction in BP from baseline) was achieved in 94 percent of patients
      treated with IV nicardipine vs 12 percent with placebo (p less than 0.001). The
      mean response time and infusion rate for IV nicardipine were 11.5 (+/- 0.8)
      minutes and 12.8 (+/- 0.3) mg/h, respectively. The magnitude of BP reduction was
      similar in both cardiac and noncardiac postsurgical patients. Blood pressure
      control was sustained with minimal dose adjustments of IV nicardipine (3.0 +/-
      0.2 mg/h) during a prolonged maintenance infusion period of 6.8 +/- 0.5 h. A
      reflex mean increase in heart rate of 5 bpm was seen in patients treated with IV
      nicardipine. Sixteen patients (15 noncardiac and one cardiac surgery) had a
      sustained heart rate of greater than 100 bpm, with a mean increase of 24 bpm from
      the baseline. In all these patients except three, tachycardia was resolved while
      receiving nicardipine. None of these patients who had development of tachycardia
      during nicardipine therapy had exhibited ST segment changes indicative of
      ischemia. One patient with tachycardia at baseline had exhibited ST segment
      depression (3 to 4 mm) during nicardipine treatment, which was resolved following
      discontinuation of nicardipine therapy and application of nitroglycerin
      (Nitropaste). Hemodynamic evaluation revealed that IV nicardipine significantly
      decreased mean arterial pressure, systemic vascular resistance, and significantly
      increased cardiac index with no change in heart rate. These hemodynamic changes
      were similar in cardiac and noncardiac surgical patients. Adverse experiences
      reported with IV nicardipine included hypotension (4.5 percent), tachycardia (2.7
      percent), and nausea/vomiting (4.5 percent). In the placebo group, the incidence
      of adverse experience was 6 percent, with an equal distribution of hypotension (2
      percent), nausea/vomiting (2 percent), and headache (2 percent). No clinically
      important changes in laboratory variables related to IV nicardipine were
      reported. In conclusion, these findings indicate that nicardipine, a titratable
      intravenous calcium channel blocker, can rapidly and effectively control
      postoperative hypertension in cardiac and noncardiac surgical patients.

PMID- 1989802
TI  - Doppler echocardiographic assessment of prosthetic aortic valve function.
      Findings in normal valves.
AB  - To determine the Doppler-derived aortic flow velocity profiles in relation to
      type of prosthetic valve and left ventricular function, 70 patients with normal
      functioning aortic prosthetic valves (group 1 = 44 patients with low-profile
      mechanical valves and group 2 = 26 patients with high-profile mechanical valves)
      were evaluated. Peak flow velocity and mean systolic gradient were inversely
      related to valve size (r = -0.72; r = -0.76) in group 1. On the other hand,
      aortic flow velocity profiles had significant correlations with left ventricular
      end-systolic dimension (r = 0.75; r = 0.76) and left ventricular fractional
      shortening (r = -0.69; r = -0.66) in group 2. Thus, aortic flow velocity profiles
      in the low-profile mechanical valve were affected by pressure gradient caused by
      the valve size, whereas the hydromechanical disadvantage of the high profile
      mechanical valve affected the left ventricular pump function and Doppler-derived
      flow velocity profiles.

PMID- 1989804
TI  - Palpation vs pen method for the measurement of skin tuberculin reaction (Mantoux
      test).
AB  - In order to test the degree of concordance between ballpoint pen and palpation
      methods of measuring the skin induration after a Mantoux tuberculin test, we
      conducted a prospective, double-blind study. We performed a Mantoux skin test in
      1,340 healthy subjects, aged 18 to 25 years, using the tuberculin PPD-RT 23, dose
      2 IU, (1/5,000), of the Pasteur Institute, equivalent to 5 TU PPD-S. The same
      experienced reader, who was able to see only the site of the test (forearm),
      measured the induration after 48 hours by the palpation method, initially, and by
      the pen method later the same day, without knowing the identity of the examined
      person. Results of the study did not show any significant difference in any range
      of the measurements (p greater than 0.1) by the two methods. We conclude that the
      pen method is as reliable as the traditional palpation method. The sensitivity
      and the specificity of the two methods are comparable. Even though our study was
      not designed to investigate the effects with an inexperienced examiner, given the
      simplicity of the pen method, it could be the method of choice, especially for
      less experienced examiners.

PMID- 1989803
TI  - Atopy and primary lung cancer. Histology and sex distribution.
AB  - Atopy, defined as the ability to develop IgE antibodies to commonly encountered
      allergens under conditions of normal exposure, has an inherited component with
      pleiotropic effects. An inverse relationship between the occurrence of atopy,
      allergy-related diseases, and cancers at specific sites has been reported. The
      familial association of primary lung cancer is most evident among women,
      nonsmokers, and those with adenocarcinomas. In order to determine whether the
      relationship between a lower prevalence of atopy among patients with lung cancer
      compared to control subjects was consistent between histologic cell types, we
      used seven common allergens to allergy prick skin test 209 community control
      subjects (46 women), 109 cases with primary squamous cell carcinoma of the lung
      (25 women), and 67 patients with primary adenocarcinomas of the lung (23 women).
      We have confirmed earlier reports of an inverse relationship between atopy and
      lung cancer risk. In analyses focusing on sex and histologic cell type, we found
      that women with adenocarcinomas were an exception and were as likely to be atopic
      as control subjects. The evidence does not support a protective role for atopy
      among these women.

PMID- 1989805
TI  - Gas exchange during maximal upper extremity exercise.
AB  - STUDY OBJECTIVE: to characterize gas exchange and cardiopulmonary performance
      during maximal progressive arm crank exercise. DESIGN: Cardiopulmonary variables
      were measured and arterial blood gases were determined in blood samples obtained
      from an indwelling radial arterial catheter during arm crank exercise (34
      watts/min). Arm crank exercise was compared to maximal leg exercise performed by
      a different but comparable group of subjects from a previous study. PARTICIPANTS:
      19 healthy young (mean +/- SEM: 20 +/- 1 yr) black males. RESULTS: Peak arm crank
      exercise resulted in lower values compared to peak leg exercise for: power (129
      +/- 2 vs 253 +/- 10 W), VO2 (2.17 +/- 0.04 vs 3.26 +/- 0.14 L/min); VCO2 (2.9 +/-
      0.11 vs 4.32 +/- 0.17 L/min); HR (168 +/- 3 vs 189 +/- 3 beats/min); AT (1.15 +/-
      0.05 vs 1.83 +/- 0.07 L/min); and VE (101 +/- 2 vs 144 +/- 8 L/min),
      respectively. Arm crank exercise (baseline vs peak) elicited an impressive
      improvement in PaO2 (85 +/- 1 to 97 +/- 1 mm Hg), no change in SaO2 (96 +/- 0.2
      to 96 +/- 0.2 percent), no significant increase in P(A-a)O2 (3 +/- 0.7 to 5 +/-
      0.9 mm Hg) and an appropriate trending decrease in VD/VT (0.22 +/- 0.01 to 0.17
      +/- 0.01). Peak arm crank values were significantly different from peak cycle
      exercise for PaO2 (82 +/- 2.2 mm Hg), SaO2 (93 +/- 0.4 percent), P(A-a)O2 (21 +/-
      1.9 mm Hg) and VD/VT (0.08 +/- 0.01). At comparable levels of VO2 for arm crank
      and cycle exercise (2.17 +/- 0.04 vs 2.26 +/- 0.08 L/min), significant
      differences were observed for PaO2 (97 +/- 1.4 vs 81 +/- 1.9 mm Hg); SaO2 (96 +/-
      0.2 vs 94 +/- 0.4 percent); P(A-a)O2 (5 +/- 0.9 vs 14 +/- 1.5 mm Hg); and VD/VT
      (0.17 +/- 0.01 vs 0.08 +/- 0.01), respectively. CONCLUSIONS: Maximal arm crank
      exercise represents a submaximal cardiopulmonary stress compared to maximal leg
      exercise. The differences in gas exchange observed at peak exercise between arm
      crank and leg exercise for the most part reflect the lower VO2 achieved. However,
      the persistence of these gas exchange differences even at a comparable level of
      VO2 suggests that factors other than VO2 may be operative. These factors may
      include differences in alveolar ventilation, CO2 production, ventilation
      perfusion inequality, diffusion, and control of breathing.

PMID- 1989806
TI  - Effect of fast vs slow intralipid infusion on gas exchange, pulmonary
      hemodynamics, and prostaglandin metabolism.
AB  - Intralipid (20 percent, 500 ml) was infused fast (5 h) or slow (10 h) randomly in
      patients with lung injury to relate changes in plasma prostaglandin (PG)
      concentrations to gas exchange and pulmonary hemodynamics. Data were collected at
      baseline, midpoint of infusion, and 2 h following infusion. Vasodilator and
      vasoconstrictor PG metabolites, 6-keto-PGF1 alpha, and thromboxane B2,
      respectively, were measured in radial arterial blood samples. Slow Intralipid
      infusion increased shunt fraction (QS/QT) without changing mean pulmonary artery
      pressure (MPAP), whereas fast Intralipid infusion increased MPAP without changing
      QS/QT. Prostaglandin levels did not change significantly during either infusion.
      However, in both groups when the PG substrate was removed, hemodynamic and
      metabolite values decreased in parallel. In conclusion, we were unable to
      demonstrate a cause and effect relationship between plasma levels of 6-keto-PGF1
      alpha and thromboxane B2 and the observed pulmonary hemodynamic response to slow
      or fast Intralipid infusion.

PMID- 1989807
TI  - The oxygen uptake-oxygen delivery relationship during ICU interventions.
AB  - There is much interest in the relationship between oxygen delivery and oxygen
      consumption in the critically ill patient. This interest is occasioned by the
      observation that patients with sepsis and the adult respiratory distress syndrome
      have a linear or "supply-dependent" relationship instead of the normally observed
      biphasic or "supply-independent" relationship. These relationships are only valid
      when subjects are at rest, since during exercise, as VO2 increases, so do DO2 and
      the oxygen extraction ratio (ER, VO2/DO2). We examined the VO2-DO2 relationship
      in a group of 16 mechanically-ventilated surgical ICU patients while they were at
      rest and during activities that increase VO2. At low levels of activity, where
      mean VO2 increased from 207 +/- 38 (SD) ml/min at rest to 241 +/- 44 ml/min,
      there were significant increases in mean DO2 but not mean ER. With the greater
      (greater than 50 percent) increases in VO2 seen with chest physical therapy,
      there were increases in both DO2 and ER. When the VO2-DO2 relationship during low
      levels of exercise and rest are plotted, a linear pattern emerges that could be
      misinterpreted as a "supply dependent" pattern. Therefore, it is important to pay
      close attention to the activity state of a patient when examining the VO2-DO2
      relationship.

PMID- 1989808
TI  - Effects of injection site on the accuracy of thermal washout right ventricular
      ejection fraction measurements in clinical and model investigations.
AB  - The purpose of this investigation was to improve the accuracy of measurement of
      thermal right ventricular ejection fraction (RVEF) using the modified Swan-Ganz
      catheter. Three serial ejection fractions (EFs) (EF1, 2, 3) and the mean were
      calculated, based on Holt's theory. RVEFs were compared between right ventricular
      (RV) and atrial (RA) injection in ten intensive care unit (ICU) patients using a
      modified catheter having RV and RA orifices (15 cm and 30 cm from the distal end,
      respectively), and paired duplicate (two patients) or triplicate (eight patients)
      measurements were performed. To determine what factors interfere with RVEF, a
      model heart (with diastolic volume of 150 ml) was constructed, in which model
      injection of cold water to the direct inflow tract (RA), to the direct mixing
      chamber (RV), or through the catheter running in the inflow tract were compared.
      When EFs were compared between RV and RA injection, those for the former were
      greater (RV vs RA in EF1 and EFmean: 0.46 +/- 0.15 vs 0.23 +/- 0.11 in EF1, and
      0.45 +/- 0.13 vs 0.28 +/- 0.11 in EFmean, mean +/- SD, p less than 0.01). When
      the serial EFs were compared in each injection type, in the RV injection EF3 was
      the smallest as was EF1 in the RA injection. The same phenomenon was observed in
      the model as in the patients, and moreover when cold water was injected in RA
      through a catheter running through the circuit, EFs were greatly underestimated
      (EF1 = 0.29 +/- 0.02 at preset EF = 0.4). We conclude that these phenomena were
      caused by sluggish movement of the cold indicator from RA to RV when injected
      into RA, and by interference with the cooled cardiac chamber and catheter.
      Consequently, the first or second EFs obtained from RV injection might be closest
      to the actual values because of the least interference with those factors.

PMID- 1989809
TI  - Effects of intravenous amphotericin B infusion on hemodynamics and airway
      mechanics in awake sheep.
AB  - To gain a better understanding of the adverse pulmonary response to amphotericin
      B administration reported in humans, we examined the effects of this agent in the
      chronically instrumented awake sheep. We measured pulmonary artery and left
      atrial pressures (Ppa and Pla), lung lymph flow (Qlymph), dynamic lung compliance
      (Cdyn), resistance to airflow across the lung (RL), lymph thromboxane B2 (TxB2),
      lymph 6-keto-PGF1 alpha, peripheral leukocyte counts, and arterial blood gases.
      After at least one hour of stable baseline (BL) observation, amphotericin B
      (Fungizone, Squibb, 1 mg/kg) was infused intravenously over 1 h. Measurements
      were continued for 3 h after the start of infusion. Amphotericin caused an
      immediate decrease in Cdyn nadiring at 55 percent of BL and an increase in Ppa
      from 21 +/- 1 mm Hg at BL to 44 +/- 4 at 30 minutes. RL increased to 5.5-fold
      over BL by 30 minutes into infusion, and lung lymph TxB2 concentrations were
      increased tenfold compared with BL by the end of the 1-h infusion (p less than
      0.05). In this same time interval, there were increases in Qlymph (1.5 ml/15 min
      at BL to 4.9 +/- 0.8), but 6-keto-PGF1 alpha concentrations did not reach maximum
      until 2 h after the start of infusion. There was a decrease in peripheral
      leukocyte count and PaO2 (80 +/- 3 mm Hg at BL to 69 +/- 4 at 1 h) that returned
      to BL over the remaining 2 h. The temporal relationship of the TxB2 peak with
      these pathophysiologic changes and previous data describing the effects of
      thromboxane in the sheep lung suggest that a component of these alterations is
      due to thromboxane release. We conclude that several pulmonary system
      abnormalities occur following amphotericin infusion in sheep and that these
      findings provide a better physiologic basis for explaining the human pulmonary
      response to amphotericin.

PMID- 1989810
TI  - Postpartum pulmonary infiltrates with peripheral eosinophilia.

PMID- 1989811
TI  - Psychosocial issues in lung cancer patients (Part 2).

PMID- 1989812
TI  - Acute pulmonary edema in a woman with a porcine mitral valve.

PMID- 1989813
TI  - Seven-pathogen tricuspid endocarditis in an intravenous drug abuser. Pitfalls in
      laboratory diagnosis.
AB  - Polymicrobial endocarditis is being reported with increasing frequency in drug
      abusers. However, the full extent of infection may be unrecognized with routine
      blood culture techniques because of the overgrowth of more fastidious organisms
      by other pathogens. This report documents an intravenous drug abuser with the
      first reported case of tricuspid valve endocarditis involving seven pathogens,
      discusses pitfalls of routine blood cultures and examines the role of the
      laboratory in microbiologic diagnosis.

PMID- 1989814
TI  - Auto-PEEP during CPR. An "occult" cause of electromechanical dissociation?
AB  - A 64-year-old man with severe COPD developed refractory nonperfusing sinus rhythm
      after intubation and positive-pressure ventilation. Fifteen minutes after
      resuscitative efforts were halted, the patient was noted to have spontaneous
      respirations and blood pressure, suggesting that dynamic hyperinflation was
      responsible for the observed electromechanical dissociation (EMD). We recommend a
      brief trial of apnea for patients with COPD and EMD when conventional measures
      are unsuccessful.

PMID- 1989816
TI  - Progressive hemolytic anemia due to delayed recognition of a Beall mitral valve
      prosthesis.
AB  - In addition to a working knowledge of general complications such as
      thromboembolism and infective endocarditis, optimal care of the patient with a
      prosthetic valve requires specific knowledge concerning the characteristics of a
      given patient's prosthesis. This may need to include the ability to identify the
      valve roentgenographically when history and records are unavailable. A 53-year
      old woman with mitral stenosis secondary to rheumatic heart disease and status
      post a reported Bjork-Shiley mitral valve (MV) replacement 17 years prior to
      hospital admission was referred for evaluation of severe hemolytic anemia.
      Previous cinefluoroscopy in 1986 at the time of a cerebrovascular accident
      revealed a normally functioning caged disc prosthesis and not the tilting disc of
      a Bjork-Shiley prosthetic valve. The valve was not further characterized and she
      continued receiving warfarin therapy until May 1989 when she presented with
      laboratory findings showing a marked hemolytic anemia with a hemoglobin of 6.5
      mg/dl and lactate dehydrogenase (LDH) value of 2100 IU. Echocardiography revealed
      normal valvular function without evidence of perivalvular leak. The patient was
      referred for further evaluation with chest roentgenogram at the time of hospital
      admission revealing a valve configuration characteristic of the Beall model
      103/104 series that has been found to manifest progressive disc variance with a
      high degree of hemolytic anemia (despite normal noninvasive evaluation of MV
      function), disc tilting with intermittent regurgitation, and catastrophic disc
      embolization in extreme cases. The precise identification of valvular prosthesis
      in patients after valve replacement is crucial for optimal management. As in our
      case, the mere identification of a particular valve may necessitate certain
      management and therapy based on the natural history of that valve. In the absence
      of reliable history and/or records, the roentgenographic examination should lead
      to the precise identification.

PMID- 1989815
TI  - Endobronchial actinomycosis simulating bronchogenic carcinoma. Diagnosis by
      bronchial biopsy.
AB  - Five cases of actinomycosis of the main bronchi or trachea which were suggestive
      clinically of bronchogenic carcinoma are described. In four patients the correct
      diagnosis was made by a bronchial biopsy or wash, or both. Three of them
      recovered following antibiotic treatment, and one died a few days after
      bronchoscopy. In one case the Actinomyces were found in the bronchial wash
      retrospectively following diagnosis of pulmonary actinomycosis in the lobectomy
      specimen. A concomitant endobronchial lipoma was found in one of the patients.
      The diagnosis of pulmonary actinomycosis by bronchial biopsy may save the patient
      major surgical intervention.

PMID- 1989817
TI  - The acute and insidious onset of pulmonary metastatic transitional cell
      carcinoma.
AB  - Transitional cell carcinoma is a common urologic neoplasm. Although pulmonary
      metastases from this tumor are often not appreciated clinically, they are
      frequently documented in autopsy studies. Therefore, the clinical recognition of
      this condition can be problematic. To illustrate this point, we present three
      patients with progressive unexplained dyspnea and histories of transitional cell
      carcinoma. Since ineffective and possibly detrimental therapeutic approaches may
      be initiated, a high index of suspicion for pulmonary metastatic embolization
      must be maintained. Early histologic identification of these metastatic emboli
      and initiation of effective chemotherapy may prove beneficial for improved
      quality of life.

PMID- 1989818
TI  - Pulmonary embolism presenting as exercise-induced hypotension.
AB  - A 68-year-old man with remote history of previous myocardial infarction presented
      with a four-week history of intermittent dyspnea. After developing hypotension
      during an exercise tolerance test, he underwent cardiac catheterization,
      revealing significant pulmonary hypertension and two-vessel coronary artery
      disease. Pulmonary angiography confirmed the presence of pulmonary emboli which
      partially resolved after thrombolytic therapy. Subsequent treadmill testing
      confirmed the absence of exercise-induced hypotension two months following
      treatment. This case underscores the importance of considering pulmonary embolism
      as a potential cause of exercise-induced hypotension, since it can be
      successfully treated with thrombolytic agents weeks after the initial onset of
      symptoms.

PMID- 1989819
TI  - Spontaneous pneumothorax in AIDS patients with recurrent Pneumocystis carinii
      pneumonia despite aerosolized pentamidine prophylaxis.
AB  - Aerosolized pentamidine prophylaxis for Pneumocystis carinii pneumonia in
      patients with the acquired immunodeficiency syndrome (AIDS) may predispose these
      patients to recurrent apical Pneumocystis infection. Bullous changes and
      pulmonary cysts develop in the lung apices due to repeated episodes of
      inflammation and cytotoxic effects of HIV on pulmonary macrophages. These changes
      progress despite prophylaxis against recurrent Pneumocystis infection with
      aerosolized pentamidine, increasing the risk of spontaneous pneumothorax. Two
      cases are presented of bilateral pneumothoraces in patients with AIDS and
      recurrent P carinii pneumonia despite aerosolized pentamidine prophylaxis.
      Patients receiving aerosolized pentamidine prophylaxis for Pneumocystis pneumonia
      appear to have an increased risk of pneumothorax due to recurrent apical
      infections with P carinii.

PMID- 1989820
TI  - Pathologic bronchial vasculature in a case of massive hemoptysis due to chronic
      bronchitis.
AB  - The cause of bleeding in a patient with recurrent massive hemoptysis was not
      apparent after bronchoscopy and gross examination of the lobectomy specimen.
      Histologic submission of all major bronchi uncovered dilated, tortuous bronchial
      arteries just below the bronchial mucosa with sites of both current and healing
      arterial rupture. This bronchial arterial abnormality is common to several
      chronic pulmonary diseases, but is rarely diagnosed as a cause of massive
      hemoptysis. Careful pathologic examination of major bronchi in the setting of
      hemoptysis of unknown causation is recommended.

PMID- 1989821
TI  - Bilateral reexpansion pulmonary edema following unilateral pleurocentesis.
AB  - Acute ipsilateral pulmonary edema following reexpansion of the lung after
      pleurocentesis or pneumothorax is a well described entity. We report the unusual
      occurrence of bilateral pulmonary edema following unilateral pleurocentesis in a
      young male without heart disease. Various hypotheses regarding the mechanism of
      reexpansion pulmonary edema include increased capillary permeability due to
      hypoxic injury, decreased surfactant production, altered pulmonary perfusion and
      mechanical stretching of membranes. This case suggests that forces leading to
      ipsilateral reexpansion pulmonary edema also affect the contralateral lung.

PMID- 1989822
TI  - Treatment of atelectasis with selective bronchial suctioning. Use of a curved
      tipped catheter with a guide mark.
AB  - We applied our technique of selective bronchial suctioning (SBS) for the
      treatment of atelectasis (AT) of middle and lower lobes; nine patients with
      refractory ATs were successfully treated. We considered that SBS using a curve
      tipped catheter with a guide mark (CTCGM) is the technique of choice for the
      treatment of refractory AT when conventional respiratory therapy is not effective
      and a bronchoscopist is not available.

PMID- 1989823
TI  - Pseudo pre-excitation with concertina effect in idioventricular tachycardia.
AB  - The concertina effect is a phenomenon where the QRS complexes reflect alternating
      phases of gradual widening and narrowing. This is most commonly due to
      ventricular pre-excitation, and the changes in QRS morphology are due to
      variability of the ventricular zone that undergoes pre-excitation. This
      presentation reflects a case where the concertina effect is due to an
      idioventricular tachycardia at a rate nearly identical to the sinus rate.
      Variable degrees of ventricular fusion therefore occur, and the concertina effect
      ensues, in relation to slight variations of the sinus cycle.

PMID- 1989824
TI  - Total left main coronary artery occlusion after aortic aneurysm repair and valve
      replacement.
AB  - A 38-year-old woman with complete occlusion of the left main coronary artery
      secondary to cannulation during aortic valve replacement is presented. The
      clinical course was characterized by progressive left ventricular dysfunction and
      congestive heart failure. Recognition of this potential problem when it occurs is
      important as to institute therapeutic measures which may interrupt a patient's
      progressive clinical deterioration.

PMID- 1989825
TI  - Cardiac tamponade and contralateral hemothorax after subclavian vein
      catheterization.
AB  - A patient developed life-threatening cardiac tamponade and contralateral
      hemothorax after insertion of a subclavian catheter in the operating room.
      Contrast was infused through the catheter, demonstrating its malposition in the
      pericardial space. Contrast infusion was valuable in evaluating this complication
      of central line placement.

PMID- 1989826
TI  - Estimation of auto-PEEP.

PMID- 1989827
TI  - Allergistis non carborundum.

PMID- 1989828
TI  - Long-term continuous infusion of labetalol.

PMID- 1989829
TI  - Use of pleural alkaline phosphatase content to diagnose tuberculous effusions.

PMID- 1989830
TI  - Metallic weakness and breakage of Abrams pleural biopsy needle.

PMID- 1989831
TI  - Control roentgenography after fiberoptic bronchoscopy.

PMID- 1989832
TI  - Bronchodilating effect of intravenous magnesium sulfate.

PMID- 1989833
TI  - Right-to-left atrial shunting.

PMID- 1989834
TI  - Pulmonary involvement in non-Hodgkin's malignant lymphomas.

PMID- 1989835
TI  - Metastatic choriocarcinoma of the lung presenting as hemothorax.

PMID- 1989836
TI  - Occupational asthma in a developing country.

PMID- 1989837
TI  - Preventing diaphragm fatigue in the ventilated patient.
AB  - Diaphragm fatigue is a physiologic consequence of acute and chronic respiratory
      conditions. By understanding the physiology of this phenomenon, the critical care
      nurse can prevent this respiratory complication in ventilated patients.

PMID- 1989838
TI  - Analysis of strategies in the management of coronary patients' pain.
AB  - This exploratory clinical investigation identified clinical practice strategies
      used by expert critical care nurses in the assessment and management of pain. The
      investigator found that nurses use short, effective questions and observations
      for cardiac pain assessment.

PMID- 1989839
TI  - Using concept analysis to enhance clinical practice and research.
AB  - Describing human responses in critical care nursing is fundamental to the
      implementation and evaluation of therapeutic interventions. This article explains
      how concept analysis facilitates care planning, communication, nursing diagnoses,
      and clinical nursing research in critical care.

PMID- 1989840
TI  - Ethics: focus for the 90s.

PMID- 1989841
TI  - Relationship of management style and anticipated turnover.
AB  - The retention of critical care nurses is an important priority of nursing
      administration. Research in business and industry has shown that management style
      is related to turnover, but documentation of this relationship is lacking for
      nurses in hospitals. This research report describes how management style is
      directly related to anticipated turnover of critical care nursing staff.

PMID- 1989843
TI  - Critical care leadership course: a recruitment and retention strategy.
AB  - This article describes how to implement a baccalaureate level course in critical
      care leadership and management and emphasizes the value of this course in
      recruiting and developing critical care nurses with leadership abilities.

PMID- 1989842
TI  - The metabolic response to injury in the surgical/trauma patient.
AB  - Following tissue injury or surgical intervention, critically ill patients
      experience metabolic alterations that may either eventually resolve or progress
      to Hypermetabolic Multiple Systems Organ Failure. An understanding of these
      processes allows critical care nurses to monitor their patients' clinical status
      following trauma or surgical intervention and fosters an appreciation of
      patients' nutritional needs.

PMID- 1989844
TI  - Asthma and chronic obstructive lung disease: a pharmacologic approach.
AB  - Changing concepts are emerging that should improve our ability to adequately
      treat asthma. This volume of Disease-a-Month reviews the triggers and the role of
      inflammation in asthma, and outlines the treatment of acute asthma as well as the
      chronic management of reversible obstructive airways disease. There is general
      agreement that sympathomimetics are the treatment of choice for acute severe
      asthma. The role of theophylline for acute symptoms has been downplayed, and the
      role of corticosteroids continues to be debated. However, most authorities agree
      that patients with severe asthma will benefit from the addition of
      corticosteroids to the program. For the chronic management of asthma,
      appreciation that inflammation is a perpetuating feature suggests that treatment
      should generally be directed toward the inflammation. Corticosteroid aerosols
      have taken on greater prominence and have been advocated as the first line of
      approach. New concepts regarding the role of allergy in the perpetuation of
      asthma and the role of immunotherapy in its amelioration also have emerged.
      Medications not previously thought to be beneficial are being actively
      investigated. They include gold, methotrexate, and even intravenous gamma
      globulin.

PMID- 1989846
TI  - Effects of gonadal steroids on clearance of growth hormone at steady state in the
      rat.
AB  - Gonadal steroids have been implicated in the modulation of GH secretory patterns
      in the rat. We have studied the effects of testosterone (T) or estradiol (E2) on
      the steady state clearance (Clss) and plasma half-life (t1/2) of GH in male and
      female rats (n = 4-6/group). A femoral and a jugular cannula were surgically
      implanted into adult Sprague-Dawley rats. At the time of cannulation some rats
      were orchidectomized, and a Silastic capsule containing E2, T, or nothing was
      implanted sc. After recovery from surgery, either purified rat GH or a crude
      extract of rat pituitary was infused iv to attain steady state plasma GH
      concentrations. Blood samples were taken every 30 min for 4 h during the
      infusion, and nine samples were taken at 2.5-min intervals immediately after
      stopping the infusion. The mean Clss for GH in female rats were significantly (P
      less than or equal to 0.001) less than that in males, whereas the t1/2 did not
      differ between the two groups. Neither the Clss nor the t1/2 was affected by
      castration in males or females. The Clss of GH in E2-treated castrated males was
      significantly less (P less than 0.001) than that for intact males, but the t1/2
      did not differ between the two groups. The Clss for GH was greater in T-treated
      ovariectomized rats than in intact females, but the t1/2 did not differ with T
      treatment. These results suggest that 1) the Clss for GH is lower in female rats
      than in males; 2) 4 weeks of gonadectomy has no effect on the Clss in males or
      females; 3) under experimental conditions, E2 decreases and T increases the Clss
      for GH; and 4) the t1/2 for GH is not different in males or females. The steroid
      induced changes in Clss in the absence of detectable effects on t1/2 suggest that
      factors affecting the volume of distribution at steady state (i.e. plasma GH
      binding proteins or GH heterogeneity) are involved in the effects of gonadal
      steroids on GH clearance in the rat.

PMID- 1989845
TI  - Augmented hypothalamic proopiomelanocortin gene expression with pubertal
      development in the male rat: evidence for an androgen receptor-independent
      action.
AB  - To investigate the mechanism(s) during pubertal development by which androgens
      alter hypothalamic proopiomelanocortin (POMC) gene expression and beta-endorphin
      content, we used the technique of in situ hybridization histochemistry and the
      androgen-insensitive testicular feminized (Tfm) rat. We evaluated POMC mRNA
      levels in the arcuate nuclei and periarcuate regions of 12 coronal brain slices
      from prepubertal (age, 30 days) and adult (age, 60 days) normal male and Tfm rats
      (n = 4 for each group). Hybridizations were performed using an 35S-radiolabeled
      oligonucleotide probe complementary to a 30-base sequence within POMC mRNA. The
      tissue sections were sequentially exposed to x-ray film and photographic emulsion
      with subsequent analysis by both densitometry and computer-assisted grain
      counting. beta-Endorphin was measured in hypothalamic tissue blocks from similar
      animals in each of the four experimental groups. The results of densitometry and
      grain counting were consistent and revealed an increase in POMC mRNA with
      pubertal development in both the male and Tfm animals. The concentration of
      hypothalamic beta-endorphin was greater for the adult Tfm animals than for all
      other groups, which did not differ from each other. These results suggest that
      androgens may stimulate POMC gene transcription by their action through estrogen
      receptors after conversion by aromatase. Alternatively, additional pubertal
      factors may be responsible for act directly through their respective receptors to
      alter translation, posttranslational processing, or secretion of beta-endorphin,
      resulting in diminished intracellular hypothalamic peptide concentration.

PMID- 1989847
TI  - Lifelong sequential changes in glucose tolerance and insulin secretion in
      genetically obese Zucker rats (fa/fa) fed a diabetogenic diet.
AB  - Life-long sequential changes in glucose tolerance and insulin secretion were
      investigated in genetically obese Zucker rats (fa/fa) fed a diabetogenic diet
      rich in lard and sucrose. Comparisons were made with lean littermates (Fa/-)
      receiving normal chow diet. At 3-month intervals, seven to nine lean and obese
      rats had two permanent venous catheters implanted, allowing stress- and pain-free
      sampling of blood before, during, and after substrate administration. Intravenous
      glucose, iv arginine, and oral glucose tolerance were tested. The obese rats
      progressively developed hyperglycemia and severe hyperinsulinemia; their basal
      glycemia reached 8.8 +/- 1.1 vs. 5.8 +/- 0.2 mmol/liter in the lean rats at 46
      weeks of age; respective insulinemia was 287.7 +/- 61.9 and 18.1 +/- 2.8 mU/liter
      (mean +/- SD). In the obese rats a distinct loss in glucose tolerance was seen
      with progression of age in spite of rising stimulated insulin secretion, which
      suggests progressive development of insulin resistance without exhaustion of B
      cell secretory capacity. Absence of insulin deficiency was also suggested by
      immunohistochemical staining of pancreatic tissue specimens from obese rats,
      which showed large populations of insulin-containing cells. Like the obese
      animals, lean rats exhibited a decrease in insulin sensitivity with age. Relating
      basal individual glycemia and insulinemia, a rise by 1 mmol/liter in glycemia was
      associated with a 8.8-fold rise in basal insulinemia in lean rats, but only with
      a 1.8-fold increase in obese rats. Similar correlations for stimulated glycemia
      and insulinemia suggest impaired glucose sensitivity of pancreatic B-cells in
      obese vs. lean rats. In conclusion, hyperglycemia and hyperinsulinemia in insulin
      resistant obese Zucker rats on a diabetogenic diet are not characterized by
      quantitatively deficient B-cell secretory capacity, but, rather, by impaired B
      cell sensitivity to glucose with qualitatively intact regulation of glycemia and
      insulinemia at elevated plasma concentrations.

PMID- 1989848
TI  - Neonatal treatment with monosodium glutamate: effects of prolonged growth hormone
      (GH)-releasing hormone deficiency on pulsatile GH secretion and growth in female
      rats.
AB  - Administration of monosodium glutamate (MSG) to neonatal rodents produces
      permanent lesions of hypothalamic arcuate neurons that secrete GH-releasing
      hormone (GHRH). The present study was intended to determine the consequences of
      GHRH deficiency on the pulsatile GH secretory pattern and growth in MSG-treated
      female rats and to compare these effects with those observed in male littermates.
      Male and female rats were injected with MSG [4 mg/g body wt (BW), sc] or saline
      (controls) on days 2, 4, 6, 8, and 10 after birth. Immunoreactive GHRH
      concentrations were decreased in the hypothalamus (by 60%) and in the median
      eminence (by 95%) of adult male and female MSG-treated rats. In contrast,
      somatostatin concentrations were unaffected. BW and linear growth were severely
      impaired in male MSG-treated rats, but in MSG-lesioned females BW was not
      different from controls, and the attenuation of longitudinal growth was less
      severe and the obesity more pronounced than in males. These sex differences
      occurred despite similar reductions (by 55%) in serum insulin-like growth factor
      I concentrations in male and female MSG-treated rats. MSG treatment also produced
      decreases in pituitary wt and GH content (by 60%), independent of sex. Pulsatile
      GH secretion was studied by serial blood sampling of chronically cannulated,
      freely moving rats. Plasma GH patterns were analyzed by the PULSAR program.
      Compared to controls, treatment with MSG led to a marked inhibition (by 90%) of
      GH secretion in both sexes. Significant reductions in GH pulse amplitude (-95%)
      and pulse duration (-62%) were observed in males, whereas pulse amplitude (-85%),
      pulse frequency (-67%), and baseline GH concentrations (-80%) were markedly
      reduced in females. The GH responses to an iv bolus injection of rat GHRH (1
      microgram/rat) was severely blunted in both male and female MSG-treated rats.
      This study demonstrates that GHRH deficiency in female rats results in a marked
      inhibition of GH pulses, as in males, but also causes severe and sex-specific
      reductions in GH basal secretion and pulse frequency. These observations suggest
      that hypothalamic GHRH secretion in female rats is more continuous than in males
      and is a determinant of the elevated interpulse secretion of GH. Moreover, body
      wt and linear growth are less severely affected by arcuate lesions in female
      animals, compared to males. These sex-related differences in growth rates may
      result in part from the tendency of female MSG-lesioned rats to become more obese
      than males, and the development of obesity, in turn, may antagonize the factors
      that tend to slow linear growth.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1989850
TI  - Infusion of neuropeptide Y into the stalk-median eminence stimulates in vivo
      release of luteinizing hormone-release hormone in gonadectomized rhesus monkeys.
AB  - Studies in the rat and rabbit indicate that facilitatory effects of neuropeptide
      Y (NPY) as well as norepinephrine (NE) on LH and LHRH release are dependent on
      the presence of the ovarian steroid estrogen. However, we have previously found
      the NE and an alpha-1-adrenergic agonist are both stimulatory to pulsatile LHRH
      release in ovariectomized rhesus monkeys. In the present experiment the effects
      of NPY on LHRH release were examined in conscious monkeys using a push-pull
      perfusion method. Twelve gonadectomized monkeys (8 females and 4 males) were
      used. Perfusate samples from the stalk-median eminence (S-ME) were obtained
      through a push-pull cannula at 10-min intervals for 12 h, and the amount of LHRH
      in samples were determined with RIA. NPY dissolved in a modified Krebs-Ringer
      phosphate buffer solution at concentrations of 10(-8), 10(-7), 10(-6), and 10(-5)
      M was directly infused into the S-ME through the push cannula for 10 min at 90
      min intervals. Vehicle was infused as a control. Since sex differences in LHRH
      response to NPY were not present, data from males and females were combined for
      analysis. NPY infusion into the S-ME stimulated LHRH release in a dose-dependent
      manner (P less than 0.001). The peak LHRH responses (mean +/- SEM) to NPY at
      different concentrations were: 10(-8) M = 2.1 +/- 0.4 pg/ml; 10(-7) M = 2.6 +/-
      0.5 pg/ml; 10(-6) M = 6.5 +/- 1.1 pg/ml; 10(-5) M = 15.1 +/- 2.9 pg/ml, whereas
      to vehicle 0.37 +/- 0.17 pg/ml. All NPY doses tested were significantly effective
      as compared to vehicle (P less than 0.01). The LHRH response to 10(-6) M was
      greater (P less than 0.01) than that of 10(-8) M or 10(-7) M, and the response to
      10(-5) M was greater (P less than 0.01) than that of all lower doses. The results
      indicate that NPY infusion into the S-ME elicits the release of LHRH in vivo in a
      dose-dependent manner in the monkey. The data further suggest that LHRH neurons
      and/or neuroterminals in the monkey are responsive to NPY stimulation in the
      absence of gonadal steroids. It is concluded that in addition to NE, NPY is an
      important regulator of pulsatile LHRH release in the nonhuman primate.

PMID- 1989849
TI  - Glucocorticoids inhibit fibronectin synthesis and messenger ribonucleic acid
      levels in cultured fetal rat parietal bones.
AB  - The effects of corticosterone on fibronectin production, bone growth, and
      morphology were examined in a mineralizing organ culture system derived from 20
      day-old fetal rat parietal bones. During 4 days of culture, 1-1000 nM
      corticosterone had no significant effect on the increase in dry weight or on DNA
      content, but 100 and 1000 nM corticosterone did inhibit the increase in calcium
      content. Light microscopic examination of the 4-day cultures demonstrated a
      glucocorticoid-induced change in osteoblast shape and organization along the
      mineralizing front of the bone. A dose-dependent inhibition of fibronectin
      secretion into the medium was determined by enzyme-linked immunosorbent assay. In
      control cultures, fibronectin production was 0.105 +/- 0.005 microgram/ml.bone at
      24 h and 0.397 +/- 0.037 microgram/ml.bone during the 72- to 96-h interval. The
      maximal inhibition of fibronectin secretion was 45% at 24 h and 70% at 96 h with
      1000 nM corticosterone. Both immunofluorescent visualization of fibronectin
      staining in the tissue and a Western blot of fibronectin in the tissue showed a
      decrease in fibronectin levels. At 24 and 96 h, a dose- and time-dependent
      decrease in fibronectin mRNA transcripts was found. At 24 and 96 h, 1000 nM
      corticosterone produced a decrease of 42% and 62%, respectively, in fibronectin
      mRNA levels. Our findings show that glucocorticoids inhibit fibronectin
      production in developing bone. The decrease in fibronectin synthesis may
      contribute to altered osteoblast organization and function during bone formation.

PMID- 1989851
TI  - Steroidogenesis by equine preovulatory follicles: relative roles of theca interna
      and granulosa cells.
AB  - Estrous cycles in mares have several unique characteristics, including the
      presence of a long period of estrus and the absence of a typical LH surge. Like
      follicles of other species, equine preovulatory follicles are characterized by
      their ability to secrete large amounts of 17 beta-estradiol, but it is not clear
      which follicular cell type is responsible for estradiol synthesis in mares. To
      better understand the relative roles of theca interna and granulosa cells in
      follicular steroidogenesis, presumptive ovulatory follicles were obtained from
      mares during early estrus (first or second day of estrus; n = 4) and during late
      estrus (fourth or fifth day of estrus; n = 4). Preparations of theca interna and
      granulosa cells were cultured for 3 days in medium with or without equine LH,
      FSH, LH plus FSH, or CG (100 ng/ml) in the presence or absence of 0.5 microM
      testosterone, and culture media were assayed for progesterone, androstenedione,
      and 17 beta-estradiol. Progesterone was the predominant steroid secreted by
      granulosa cells in the absence of exogenous testosterone. Its accumulation was
      significantly higher in cultures of granulosa cells from late vs. early estrus (P
      less than 0.05), and all gonadotropins stimulated progesterone secretion at both
      stages of follicular development (P less than 0.05). In contrast, granulosa cells
      secreted very low amounts of androstenedione in vitro, and only very small
      amounts of 17 beta-estradiol were produced when cells were cultured in medium
      without testosterone. However, the addition of testosterone caused a 170-fold
      increase over control values in estradiol accumulation over 3 days of culture (P
      less than 0.0001), clearly indicating the presence of a very active aromatase
      enzyme system in equine granulosa cells. Steroid secretion by theca interna
      differed in several respects from secretion by granulosa cells. Theca interna
      from early and late estrous follicles secreted negligible amounts of progesterone
      in vitro, and equine gonadotropins had no effect on its secretion. Also, theca
      interna secreted only small amounts of estradiol in vitro, and its accumulation
      was not increased by the addition of exogenous testosterone. Also, in contrast to
      granulosa cell cultures, androstenedione was the predominant steroid secreted by
      theca interna from early and late estrous follicles. In conclusion, this study
      does not support the current model of equine follicular steroidogenesis, which
      holds that 17 beta-estradiol biosynthesis derives primarily from the theca
      interna layer.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1989852
TI  - Internucleosomal deoxyribonucleic acid cleavage activity in apoptotic thymocytes:
      detection and endocrine regulation.
AB  - Apoptosis is a programmed form of cell death that occurs under numerous
      physiological conditions, including endocrine regulation of specific cell
      populations. We have investigated the biochemical mechanisms involved in
      glucocorticoid-induced apoptosis in rat thymocytes. Internucleosomal cleavage of
      chromatin into oligonucleosomal fragments is common to all forms of apoptosis and
      precedes the onset of cell death. To identify the endonuclease that is
      responsible for the specific pattern of DNA degradation in glucocorticoid-induced
      apoptosis, we have developed an assay to measure internucleosomal cleavage
      activity in thymocyte nuclear extracts. This assay uses nuclei from cells
      resistant to hormone-induced DNA fragmentation (HeLa cells) as a substrate for
      nuclear extracts prepared from thymocytes of adrenalectomized rats treated with
      either dexamethasone (dex) or vehicle (control). After incubation at room
      temperature for 90 min, the HeLa DNA is purified, and its integrity is analyzed
      by agarose gel electrophoresis. The appearance of internucleosomal fragments of
      HeLa DNA is indicative of nuclease activity in the thymocyte nuclear extract.
      Nuclear extracts prepared from thymocytes of rats treated with dex for 5 h caused
      internucleosomal cleavage of HeLa DNA, whereas extracts from control rats did not
      result in any DNA fragmentation. Regulation of nuclease activity by dex was time
      dependent. Internucleosomal cleavage activity in thymocyte extract from dex
      treated animals was detected as early as 2 h after hormone treatment and occurred
      before any detectable change in cell viability. Maximal extractable nuclease
      activity was coincident with decreased thymocyte viability and thymic involution.
      In contrast, extracts from medullary thymocytes, which are the only thymocytes
      that survive 72 h of glucocorticoid treatment, did not contain nuclease activity
      by this assay. Regulation of internucleosomal cleavage activity by dex was dose
      dependent and was specific for the glucocorticoid class of steroid hormones.
      Furthermore, the dex-induced response was inhibited by pretreating rats with the
      glucocorticoid receptor antagonist RU486, indicating that receptor-mediated
      processes are involved in the regulation of nuclease activity. The similarities
      between the regulation of internucleosomal cleavage activity reported here and
      the previously described degradation of thymocyte DNA in vivo makes this nuclease
      a likely constituent of the apoptotic process.

PMID- 1989853
TI  - Rights to due process in instances of possible scientific misconduct.

PMID- 1989854
TI  - Gram-negative infection increases noninsulin-mediated glucose disposal.
AB  - Peripheral glucose uptake can occur by either insulin- or noninsulin-mediated
      mechanisms, and the two pathways appear to be regulated independently. Using the
      euglycemic hyperinsulinemic clamp technique, we have previously demonstrated that
      sepsis induces whole body insulin resistance. The purpose of the present study
      was to determine whether infection also alters noninsulin-mediated glucose uptake
      (NIMGU) and, if so, which tissues are affected. Studies were performed in
      chronically catheterized conscious rats under either basal (6 mM glucose, 30
      microU/ml insulin) or insulinopenic conditions to determine NIMGU. Hypermetabolic
      sepsis was induced by sc injections of live Escherichia coli, and 24 h later a
      tracer amount of [U-14C]deoxy-2-glucose was injected for the determination of the
      in vivo glucose metabolic rate (Rg) in selected tissues. Our results indicate
      that NIMGU is the predominant route of glucose disposal in both septic and
      nonseptic rats, accounting for 79-83% of the total rate of glucose disposal.
      Because the rate of whole body glucose disposal was increased by sepsis, the
      absolute rate of NIMGU was 46% higher in septic rats than in nonseptic animals.
      This increase was the result of the elevated Rg in liver, spleen, ileum, and
      lung. Sepsis also increased whole body insulin-mediated glucose uptake by 88%
      under basal conditions, and this was due to an enhanced glucose uptake by muscle
      and skin. In insulinopenic animals in which the plasma glucose concentration was
      elevated to 17 mM, whole body glucose disposal increased by 107% in nonseptic
      animals, but by only 32% in septic rats. The hyperglycemic-induced increment in
      organ Rg was smaller in all tissues examined from septic animals. However, the
      absolute rate of whole body and tissue glucose utilization was not different
      between the two groups. These results indicate that gram-negative infection
      increases whole body NIMGU, which results from an enhanced rate of glucose
      utilization by tissues rich in mononuclear phagocytes, including the liver,
      spleen, ileum, and lung, but not by muscle.

PMID- 1989855
TI  - Retinoic acid is able to reinitiate spermatogenesis in vitamin A-deficient rats
      and high replicate doses support the full development of spermatogenic cells.
AB  - The effect of various doses of retinoic acid (RA) on the seminiferous epithelium
      in vitamin A-deficient rats has been studied. Although it was generally thought
      that RA was not able to reinitiate spermatogenesis in vitamin A-deficient rats,
      one injection of 5 mg RA strongly stimulated the proliferative activity of A
      spermatogonia within 24 h, as evidenced by a 7-fold increase in the number of
      bromodeoxyuridine-labeled A-spermatogonia. Ten days after RA administration, B
      spermatogonia or preleptotene spermatocytes were seen in most of the seminiferous
      tubules. After 15 days, zygotene spermatocytes were present. Hence, RA is able to
      induce a massive and synchronized development of A-spermatogonia into
      spermatocytes. When RA was given once, combined with a RA-containing diet, only
      few of the zygotene spermatocytes present on day 15 were able to develop into
      pachytene spermatocytes, which did not develop into spermatids. In subsequent
      epithelial cycles new B-spermatogonia and spermatocytes were formed, although in
      lower numbers than during the first cycle after RA injection. When RA was given
      once a week, the formation of B-spermatogonia and preleptotene spermatocytes
      continued at a higher level. Also, more pachytene spermatocytes were formed, some
      of which were able to develop into spermatids. Finally, when RA was injected
      twice a week, even more pachytene spermatocytes and round spermatids were found
      after 36 days, and after 49 days elongated spermatids were found in all animals.
      It is concluded that RA, similar to retinol, is able to induce synchronous
      proliferation and differentiation of A-spermatogonia. When repeated injections
      are given, RA is able to support the full development of spermatogenic cells into
      elongated spermatids.

PMID- 1989856
TI  - Posterior pituitary lobectomy chronically attenuates the nocturnal surge of
      prolactin in early pregnancy.
AB  - The posterior pituitary gland contains a potent PRL-releasing factor (PRF). The
      aim of this study was to determine whether this PRF was involved in the
      luteotropic PRL surges of early pregnancy. The posterior pituitary was removed
      from a group of rats at least 4 weeks before the experiment (LOBEX). LOBEX rats
      were tested for diabetes insipidus and checked postmortem for the absence of
      posterior lobes. Plasma samples were taken from these chronically LOBEX rats as
      well as from sham-operated and unoperated controls beginning at noon on day 3 of
      pregnancy and continuing for 3 days at times most likely to demonstrate the twice
      daily surges of PRL secretion. PRL in all groups was basal (less than 12 ng/ml)
      at noon and rose to a diurnal peak at 1800 h. While the unoperated and sham
      operated controls then displayed a clear nocturnal surge of PRL, peaking at 300
      400 ng/ml at 0300 h, LOBEX rats had a significantly attenuated peak of 102.7 +/-
      17.7 ng/ml (P less than 0.001). On subsequent nights the nocturnal peaks were
      similarly attenuated in LOBEX rats, averaging 80.3 and 42.1 ng/ml on days 5 and
      6, respectively. LOBEX rats all had normal sized litters, but lactation yields
      were depressed. These data support the hypothesis that the posterior pituitary
      secretes a potent PRL-releasing factor because its removal partially blocked the
      mating-induced nocturnal surge of PRL.

PMID- 1989858
TI  - Lactation abolishes corticotropin-releasing factor-induced oxytocin secretion in
      the conscious rat.
AB  - We have assessed the response of plasma oxytocin (OT) to intracerebroventricular
      CRF-41 in both virgin female and lactating rats. In virgin rats CRF-41 resulted
      in an increase in plasma OT from 5-30 min after administration. In lactating
      rats, however, there was a complete abolition of the OT response, even at the
      highest dose of CRF-41. These data demonstrate another feature of the hormone
      nonresponsiveness apparent during lactation and suggests that one of the reasons
      for the lack of stress responses could be a down-regulation of the response to
      endogenously released CRF-41.

PMID- 1989857
TI  - Induction of the messenger ribonucleic acid for proenkephalin A in cultured
      murine CD4-positive thymocytes.
AB  - Although proenkephalin A (PEA) messenger RNA (mRNA) has been detected in many
      types of immune cells, little understanding exists about its role or the role of
      enkephalin peptides in immune responses. We have studied the expression of PEA
      mRNA during thymocyte maturation by identifying the subpopulation of thymocytes
      that expresses PEA mRNA. PEA mRNA was induced in unfractionated murine thymocytes
      after in vitro activation of these cells with the T cell mitogen, concanavalin A
      (Con-A). A slight induction of PEA mRNA was seen after 48 h of Con-A stimulation;
      however, the maximal response occurred after 72 h of culture with Con-A. Two PEA
      mRNA bands were present in unfractionated thymocytes which had been cultured with
      Con-A for 48 and 72 h. The predominant band was 1.4 kilobases (kb), and a second
      band was approximately 1.7 kb. Fractionation of thymocytes into CD4, CD8, and
      double negative subpopulations showed that only the 1.4 kb PEA mRNA was inducible
      in the mature CD4 subpopulation. Induction required the presence of antigen
      presenting cells in addition to CD4 thymocytes. Neither the 1.4 kb nor the 1.7 kb
      PEA mRNA was induced in the CD8 or double negative subpopulations. In contrast to
      the action of Con-A on murine thymocytes, PEA mRNA was not induced by this
      mitogen in murine splenic mononuclear cells at 24, 48, or 72 h. The regulated
      expression of PEA mRNA in murine thymocytes, but not in peripheral T lymphocytes,
      suggests a role for PEA mRNA and its peptides in thymocyte maturation.

PMID- 1989859
TI  - Inhibition of mitogen-stimulated proliferation of murine splenocytes by a novel
      neuropeptide, pituitary adenylate cyclase activating polypeptide: a comparative
      study with vasoactive intestinal peptide.
AB  - Two novel polypeptides known as pituitary adenylate cyclase activating
      polypeptide with 38 residues (PACAP38) and a shorter form of the peptide
      corresponding to the N-terminal 27 residues (PACAP27) were isolated from ovine
      hypothalamus. The N-terminal 28 residues of PACAP show 68% homology with
      vasoactive intestinal peptide (VIP). VIP has been reported to have specific
      binding sites in lymphocytes and inhibit mitogen-stimulated lymphocyte
      proliferation through a receptor-mediated stimulation of cAMP-dependent protein
      kinase. Using concanavalin A-induced proliferation of murine splenocytes as a
      model system, we now report that both PACAP38 and PACAP 27 can inhibit the
      proliferation of these cells in the same dose-dependent manner as VIP. The
      minimal effective concentration of the PACAPs was 10(-10)-10(-9) M. However,
      neither PACAP affected lipopolysaccharide-induced proliferation of murine
      splenocytes. The binding of [125I]PACAP27 to these splenocytes was rapid, time
      dependent, reversible, and proportional to the numbers of murine splenocytes.
      Scatchard analysis of displacement of the bound tracer by unlabeled PACAP27
      indicated the existence of two classes of binding sites. The dissociation
      constant (Kd) was 0.86 +/- 0.24 nM and the maximal binding capacity (Bmax) was
      1.13 +/- 0.39 fmol/10(6) cells for the high affinity binding site. The low
      affinity binding site had a Kd of 0.13 +/- 0.03 microM with a Bmax of 73.5 +/-
      9.5 fmol/10(6) cells. PACAP38 and VIP displaced the binding of [125I]PACAP27 in
      the same manner as PACAP27 and Scatchard analyses indicated the presence of two
      classes of binding sites with Kd and Bmax similar to those for PACAP27.
      Furthermore, when [125I]VIP was used as a radiolabeled ligand, PACAP27 and
      PACAP38 displaced the [125I]VIP binding to the same degree as unlabeled VIP.
      Scatchard analysis indicated that there was no significant difference of the Kd
      or Bmax between PACAP and VIP. Taken together, these data suggest that PACAPs
      bind to a site similar or identical to that used by VIP which inhibit the
      proliferation of murine splenocytes induced by concanavalin A.

PMID- 1989860
TI  - [125I]Bolton-Hunter neuropeptide-Y-binding sites on folliculo-stellate cells of
      the pars intermedia of Xenopus laevis: a combined autoradiographic and
      immunocytochemical study.
AB  - It has previously been established that neuropeptide-Y (NPY) is a potent
      inhibitor of alpha MSH release from the pars intermedia of the amphibian Xenopus
      laevis. The location of binding sites for NPY in the pars intermedia of the
      pituitary has now been studied with light microscopic autoradiography, using a
      dispersed cell labeling method with the specific NPY receptor ligand [125I]Bolton
      Hunter NPY. The majority of radioactive labeling was associated with folliculo
      stellate cells; the percentage of labeling as well as the mean number of grains
      were approximately 5 times higher for folliculo-stellate cells than for
      melanotropes. An excess of nonlabeled NPY drastically reduced radiolabeling of
      folliculo-stellate cells, but had no effect on the degree of labeling of
      melanotropes. These results show that folliculo-stellate cells of X. laevis
      possess specific binding sites for NPY and indicate that NPY exerts its
      inhibitory action on the release of alpha MSH in an indirect fashion, by acting
      on the folliculo-stellate cells.

PMID- 1989861
TI  - Normal differentiation of prolactin cells in neonatal rats requires a maternal
      signal specific to early lactation.
AB  - This laboratory has previously demonstrated that PRL-secreting cells are
      virtually nonexistent on day 3 but appear in appreciable numbers on day 4 of
      neonatal life. The purpose of the present study was to determine whether this
      explosive appearance of PRL cells is due to maternal influences specific to the
      first 4 days of lactation. Litters of 1-day-old rat pups were placed with foster
      mothers that had been lactating for either 1 or 4 days. Four days later (at 5
      days of age), the anterior pituitaries from these pups were removed, dispersed
      into individual cells with trypsin, and subjected to reverse hemolytic plaque
      assays for PRL and GH release. We found that the proportion of PRL-releasing
      cells in pituitaries from pups placed with day 1 mothers (4.2 +/- 0.6%; mean +/-
      SE; n = 4 experiments) was similar to that in 5-day-old pups that had not been
      fostered (3.4 +/- 0.6%; n = 3 experiments). In contrast, placing 1-day-old pups
      with day 4 mothers significantly reduced (P less than 0.01) the fraction that
      released PRL to 0.6 +/- 0.2% of all pituitary cells (n = 4 experiments). This
      effect appeared to be specific to PRL cells, since the percentage of all
      pituitary cells that secreted GH was not different between litters fostered onto
      day 1 or day 4 dams (40.0 +/- 3.8% and 41.1 +/- 3.9%, respectively; n = 3
      experiments). Furthermore, the suppression of PRL cell expression did not result
      from a gross nutritional deficit, since the rates of body wt gain during the
      foster period were not different between the two groups (12.4 +/- 0.5 and 12.9 +/
      0.8 g/litter.day, respectively; n = 4 experiments). In a second design, newborn
      pups were placed with females that had been lactating for 0, 2, 4, or 7 days and
      analyzed for PRL- and GH-releasing cells at 5 days of age. In two trials of this
      experiment, the fractions of pituitary cells that secreted PRL were 5.2, 6.3,
      5.9, and 1.2%, respectively for trial 1 and 3.3, 4.1, 0.7, and 0.6%, respectively
      for trial 2. As in the first experiment, the proportion of GH-releasing cells and
      the rate of growth were not different among the four groups. Taken together,
      these results indicate that normal differentiation of PRL cells in neonatal rats
      is triggered by a maternal signal present during the first few days of lactation,
      and that the magnitude of this signal declines with the progression of lactation.

PMID- 1989862
TI  - Tetrodotoxin augmentation of secretagogue-induced luteinizing hormone secretion.
AB  - Gonadotrophs are known to possess voltage-sensitive Na channels. We used two
      experimental systems, proestrous rat anterior pituitary tissue superfusion and 17
      beta-estradiol-treated rat anterior pituitary cells in primary culture, to
      examine the effect of Na channel inhibition on LH secretion. We found that a
      blocker of voltage-sensitive Na channels, tetrodotoxin (TTX), significantly
      augments LHRH- and elevated extracellular [K+]-induced LH secretion 20-90%. The
      augmentation of LHRH-induced secretion was demonstrable for both experimental
      systems and was independent of the time of TTX exposure. These results differ
      from previous studies in which TTX was without effect or was found to inhibit LH
      secretion. These discrepancies may be explained, in part, by the demonstration
      that TTX augmentation requires relatively low TTX concentrations (10(-6)-10(-8)
      M) and is not demonstrable at higher concentrations, requires submaximal LHRH
      concentrations (10(-10)-10(-9) M), and requires exposure of cultured cells to 17
      beta-estradiol. The site of TTX action could be either directly on gonadotroph
      voltage-sensitive Na channels or indirect via modulation of Na channels of a
      paracrine modulator of gonadotroph function. The mechanism by which TTX Na
      channel blockade augments secretagogue-induced LH secretion is unknown; however,
      the data are interpreted as favoring direct action of TTX on the gonadotroph,
      with Na channel blockade affecting a site or sites common to both LHRH and
      elevated extracellular [K+]. Whether the inhibition of Na channels is one of the
      several effects of LHRH-receptor interaction remains to be determined.

PMID- 1989863
TI  - Measurement of insulin-like growth factor-II in physiological fluids and tissues.
      I. An improved extraction procedure and radioimmunoassay for human and rat
      fluids.
AB  - The measurement of serum insulin-like growth factors (IGFs) in serum is
      complicated by the presence of high affinity IGF-binding proteins. The accurate
      measurement of IGFs by radioligand binding assays requires that the interference
      from binding proteins be eliminated. Acid-gel chromatography, the standard method
      for removing binding proteins, is laborious and time consuming. Alternative
      methods for extracting serum IGFs include the use of HCl-ethanol treatment and
      reverse phase minicolumns. However, these methods are unsuitable for use with
      serum for some species, such as rat and sheep, due to incomplete removal of
      binding proteins. We developed a fast protein liquid chromatography size
      exclusion chromatographic method for characterizing the presence of IGF-binding
      proteins in physiological fluids and used this method to systematically
      investigate different combinations of acids and organic solvents as potential
      extraction methods for IGFs. We developed and validated an improved extraction
      procedure that uses formic acid, Tween-20, and acetone. The new extraction method
      was used in conjunction with purified biosynthetic human IGF-II and a
      commercially available anti-IGF-II monoclonal antibody in the development of an
      improved RIA for IGF-II. The new RIA is sensitive (5.0 pg/tube), specific (IGF-I
      cross-reactivity, less than 1%), and reproducible [interassay precision
      (coefficient of variation), less than 9.2%). We measured the serum concentrations
      of IGF-II in adults and found a significant difference between normal subjects
      and individuals with insulin-dependent diabetes mellitus.

PMID- 1989864
TI  - Measurement of insulin-like growth factor-II in physiological fluids and tissues.
      II. Extraction quantification in rat tissues.
AB  - The tissue distribution and developmental patterns of insulin-like growth factor
      II (IGF-II) have not been investigated in rat tissues, primarily because of the
      lack of an efficient extraction method for IGF-II and a sensitive RIA. IGF-II was
      extracted from rat tissues by formic acid, and the extract was heated at an
      acidic pH and treated with acetone. The removal of binding proteins was
      demonstrated by fast protein liquid chromatography size exclusion column and the
      elimination of a dilutional bias in the RIA. Using rat IGF-II as standard, we
      optimized a RIA for the quantification of IGF-II in rat tissues. In adult rats,
      IGF-II was found in all 15 tissues examined, with the highest concentration in
      the pituitary, followed by kidney, seminal vesicles, intestine, and serum. This
      distribution is not only different from that of IGF-I, but also differs from that
      reported for IGF-II mRNA and IGF-II receptors, suggesting that the rates of
      synthesis and/or metabolism of IGF-II are tissue dependent. Developmentally, IGF
      II levels fell postnatally in most tissues, a pattern similar to that of IGF-II
      mRNA and IGF-II receptor. This developmental pattern supports the hypothesis that
      IGF-II is important in early growth and development. A relatively homogeneous
      distribution was observed in the adult rat brain, a distribution also different
      from that reported for IGF-II mRNA. In the pituitary, the highest concentration
      was found in the posterior pituitary, followed by the intermediate and anterior
      pituitary. In conclusion, IGF-II is found in many tissues of adult rats. This
      observation supports an autocrine and/or paracrine roles for IGF-II.

PMID- 1989865
TI  - Glucocorticoid regulation of the humoral immune system. Dexamethasone stimulation
      of secretory component in serum, saliva, and bile.
AB  - Dexamethasone, a potent synthetic glucocorticoid, has been shown to increase
      polymeric immunoglobulin A (IgA) and antigen-specific IgA antibody levels in
      serum. This response coincided with a decline in IgA and IgG levels in saliva and
      vaginal secretions after dexamethasone treatment. To investigate the mechanism(s)
      of glucocorticoid action responsible for the accumulation of polymeric IgA in
      serum, we undertook in the present study to determine whether dexamethasone
      alters the production of secretory component (SC). SC is the receptor responsible
      for transporting IgA from blood and tissues into bile and external secretions.
      Dexamethasone administered in vivo increased SC levels in serum in a dose- and
      time-dependent manner. When bile and saliva samples were analyzed, dexamethasone
      treatment increased saliva SC levels and the production rate of SC by the liver,
      but had a pronounced inhibitory effect on both bile and salivary levels of IgA.
      As judged by HPLC, the majority of SC in blood was associated with polymeric IgA
      and not with monomeric IgA. Immunoblots showed the presence of a 29/27K doublet
      band of SC in serum from control- and dexamethasone-stimulated rats. These
      findings indicate that the elevation of polymeric IgA levels in serum after
      dexamethasone treatment may be due to decreased clearance of IgA into bile.
      Further, it demonstrates that liver production rate of SC as well as saliva and
      serum SC levels increase with glucocorticoid treatment. This findings suggests
      that glucocorticoids, which are known to stimulate hepatocyte SC synthesis in
      vitro, increase SC levels in blood, possibly as SC fragments that are capable of
      binding polymeric IgA and retarding its clearance from blood to bile.

PMID- 1989866
TI  - Binding and action of insulin-like growth factor I in pituitary tumor cells.
AB  - Insulin-like growth factor I (IGF-I), a target hormone mediating most of the
      growth effects of GH, suppresses GH gene expression in a feedback regulatory
      loop, which may be either endocrine or paracrine in nature. Although IGF-I has
      been shown to directly attenuate GH gene transcription, the relationship of IGF-I
      binding and action in the somatotroph cell remains unclear. Therefore, IGF-I
      binding and action were compared in two different pituitary cell lines both
      secreting GH. Recombinant human IGF-I attenuated GH secretion in GC cells by up
      to 70% after 48 h in a dose-dependent manner. Surprisingly, IGF-I failed to
      suppress GH secretion in GH3 cells, a clonally related pituitary cell line.
      Binding studies showed that although the KD for IGF-I was similar in both cell
      types, GC cells contain 3-fold more IGF-I binding sites compared to GH3 cells,
      possibly explaining their resistance to IGF-I action. Nevertheless, both cell
      lines possessed abundant and similar binding sites for insulin. These results
      imply that the IGF-I signal for GH gene regulation is receptor-mediated and
      directly correlated with the number of pituitary IGF-I binding sites.
      Availability of pituitary IGF-I binding sites may therefore be important in
      determining the level of GH expression by the somatotroph.

PMID- 1989867
TI  - Failure of insulin-like growth factor-I (IGF-I) infusion to promote growth in
      protein-restricted rats despite normalization of serum IGF-I concentrations.
AB  - Dietary protein restriction in young rats induces GH resistance characterized by
      growth arrest and low serum insulin-like growth factor-I (IGF-I) concentrations.
      To determine whether the low serum IGF-I concentrations are responsible for the
      stunted growth, we infused 4-week-old protein-restricted rats with recombinant
      human IGF-I (300 micrograms/day) or rat GH (200 micrograms/100 g body wt/day) by
      osmotic minipump for 1 week. Despite the normalization of serum IGF-I
      concentrations by IGF-I infusion, carcass growth was not stimulated. In contrast,
      growth of the spleen and kidney was enhanced (+45% and +28%, respectively). Serum
      IGF-binding protein 3 (IGFBP-3), the principal carrier of IGF-I in the serum at
      this age, is decreased by 34% in protein-restricted animals and restored to
      normal by IGF-I infusion. Contrary to the selective effects of IGF-I on growth of
      protein-restricted rats, well nourished hypophysectomized rats infused with 150
      micrograms/day recombinant human IGF-I showed a significant growth response,
      including carcass and organ growth and normalization of IGFBP-3 values. These
      responses indicate that our IGF-I preparation and mode of delivery were
      effective. We conclude that: 1) dietary protein restriction causes organ-specific
      resistance to the growth-promoting properties of exogenous IGF-I; 2) IGF-I
      mediates the stimulatory effects of growth hormone on IGFBP-3 synthesis; and 3)
      the absence of carcass growth in the presence of normal serum IGF-I
      concentrations during infusion of IGF-I suggests that the growth arrest that
      accompanies protein restriction is mediated in part by resistance to IGF-I.

PMID- 1989868
TI  - Sexual dimorphism of pancreatic beta-cell degeneration in transgenic mice
      expressing an insulin-ras hybrid gene.
AB  - The human H-ras oncogene induces cell degeneration and diabetes when expressed in
      pancreatic beta-cells in transgenic mice. The disease develops predominantly in
      male mice between 5-8 months of age. Most transgenic female mice do not manifest
      this phenotype, even at much greater ages. However, ovariectomy induces female
      beta-cell degeneration similar to that in the males. In contrast, castration or
      the presence of the testicular feminization mutation do not alter the course of
      the disease in males. Treatment of males and ovariectomized females with estrogen
      prevents the development of diabetes. These results suggest that testicular
      androgens and a functional testosterone receptor are not required for the
      increased susceptibility of male beta-cells to the effects of the Ras
      oncoprotein, and that the relative resistance of female beta-cells is mediated by
      estrogen. In addition, a genetic component of female beta-cell resistance to Ras
      is revealed by crossing the transgenic mice with C3HeB/FeJ mice, which results in
      a pronounced increase in the incidence of female diabetes.

PMID- 1989869
TI  - Peptide-YY, a new partner in the negative feedback control of pancreatic
      secretion.
AB  - Peptide YY (PYY), a newly discovered ileocolonic peptide, is released by
      nutrients in the proximal and distal intestine and inhibits pancreatic secretion.
      However, it is not clear whether PYY can be released in the absence of nutrients
      in the intestine or whether a physiological role exists for endogenous PYY in
      negative feedback regulation of pancreatic secretion by pancreatic proteases. In
      the present study we measured plasma PYY concentrations and determined the
      effects of anti-PYY serum during stimulation of pancreatic secretion by
      pancreatic juice diversion (PJD). The effect of SMS 201-995 (SMS; an analog of
      somatostatin), another inhibitor of pancreatic secretion, on regulation of PYY
      release induced by PJD was also investigated. Male Wistar rats equipped with
      pancreatic, biliary, duodenal, and jugular venous cannulas were studied 4-6 days
      postoperatively. After 90 min of basal collection, pancreatic juice was diverted
      for 4 h with or without infusion of SMS (2 micrograms/kg.h), given either iv or
      intraduodenally (ID). Plasma PYY concentrations were significantly increased from
      a basal level of 177 +/- 15 pg/ml to a peak level of 328 +/- 43 pg/ml 2 h after
      PJD. These increases in PYY concentration paralleled those in pancreatic protein
      and fluid outputs. Both iv and ID infusion of SMS during the first 2 h of PJD
      markedly decreased the plasma PYY concentration to 134 +/- 27 pg/ml and 156 +/-
      19 pg/ml, respectively; the total incremental PYY release during 4 h of PJD was
      inhibited by 100% and 84% by iv and ID SMS, respectively. One milliliter of anti
      PYY serum given iv significantly augmented the increment in protein and fluid
      output during PJD. These results suggest that endogenous PYY released by PJD may
      play a physiological role in negative feedback regulation of pancreatic secretion
      in rats.

PMID- 1989870
TI  - Pituitary insulin-like growth factor-I content and gene expression in the
      streptozotocin-diabetic rat: evidence for tissue-specific regulation.
AB  - Insulinopenic diabetes mellitus in the rat is associated with reduced circulating
      levels of insulin-like growth factor-I (IGF-I), resulting primarily from
      decreased IGF-I synthesis in liver and extrahepatic sites. Plasma GH levels in
      these animals are also suppressed, with loss of episodic secretion and decreased
      pituitary synthesis. Intrapituitary IGF-I has been postulated to exert local
      autocrine/paracrine negative feedback regulation on GH synthesis and secretion.
      The present studies were designed to examine regulation of pituitary IGF-I
      peptide content and gene expression in insulinopenic streptozotocin (STZ)
      diabetic rats compared to that in liver and testis. Serum IGF-I levels were
      reduced by 86% in STZ-diabetic rats together with reduction of IGF-I content in
      liver (53%) and testis (74%; all P less than 0.001 vs. control). Concomitantly,
      liver and testicular IGF-I mRNA levels were reduced by 90% (P less than 0.001 vs.
      control). Insulin treatment restored IGF-I peptide levels in serum, liver, and
      testis toward normal, with a partial but significant increase in liver IGF-I
      mRNA. In contrast, pituitary IFG-I peptide content increased by 69% in STZ
      diabetic rats (P less than 0.001 vs. control), with no change in IGF-I gene
      expression. Insulin treatment completely reversed the rise of pituitary IGF-I
      peptide content. These results demonstrate a novel discordance in the regulation
      of IGF-I gene expression and peptide content between pituitary and other tissues
      in STZ-induced diabetic rats. Elevated IGF-I levels in the pituitaries of these
      animals may partly explain the suppressed GH synthesis and secretion seen in STZ
      diabetic rats and provide further evidence for a potential autocrine or paracrine
      role of pituitary IGF-I in GH regulation.

PMID- 1989871
TI  - Growth hormone regulation in primary fetal and neonatal rat pituitary cell
      cultures: the role of thyroid hormone.
AB  - GH is first detectable in the fetal rat pituitary between gestational days 18 and
      19. The reasons for the GH surge soon after birth and subsequent postnatal
      decline to adult levels remain unclear. We therefore determined whether GH gene
      regulation in the developing pituitary could be distinguished from adult rat
      somatotroph function. In primary cultures of fetal and neonatal rat pituitary
      cells, GH secretion was detected by the 20th gestational day. These cells were
      stimulated by GH-releasing hormone (GHRH), but not by T3 or the morphogen
      retinoic acid. The stimulatory effect of T3 (0.25 mM) on GH secretion was
      detected only on the 2nd neonatal day and was similar to that seen in mature rat
      pituitary cell cultures. GHRH (10 nM) treatment for 24 h caused a 5-fold
      induction of GH secretion in pituitary cells derived from 2-, 5-, and 12-day-old
      neonatal rats. The presence or absence of T3 in the culture medium did not alter
      the response to GHRH. In contrast, only 2-fold induction of GH was observed in
      adult male pituitary cells during the same time course. Insulin-like growth
      factor-I (IGF-I; 6.5 nM), the peripheral target hormone for GH, resulted in a
      modest (20%) attenuation of GH secretion from pituitary cells derived from 20-day
      old fetuses. IGF-I, however, produced a 70% reduction in GH levels in adult male
      pituitary cells grown under similar conditions. The effects of IGF-I on adult
      pituitary cells grown in T3-depleted medium were blunted. Addition of T3
      partially restored the responsiveness of these cells to IGF-I. The results
      suggest that the high circulating GH levels in the fetal and neonatal rat may be
      secondary to relative insensitivity of the immature somatotroph to the inhibitory
      actions of IGF-I in addition to enhanced responsiveness to GHRH compared with the
      adult rat pituitary. Relative thyroid hormone deficiency in the immature rat may
      be contributory to this early transient state of pituitary IGF-I resistance.

PMID- 1989872
TI  - Positive cotranscriptional regulation of intestinal calbindin-D28K gene
      expression by 1,25-dihydroxyvitamin D3 and glucocorticoids.
AB  - The steroid hormone 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] induces expression of
      the gene encoding calbindin-D28K, a protein involved in intestinal Ca2+
      transport. Glucocorticoids stimulate intestinal development and function, and
      presumed interaction with 1,25-(OH)2D3 has been intensively studied. Most studies
      involved administration of high doses of glucocorticoids in vivo, which inhibits
      intestinal Ca2+ transport by an unknown mechanism. However, it is now known from
      studies of the duodenal organ culture model that low concentrations of
      glucocorticoids enhance 1,25-(OH)2D3-dependent calbindin-D28K biosynthesis and
      Ca2+ transport. High concentrations mimic the action of administered
      glucocorticoids in vivo, suggesting that a distinct pharmacological or toxic
      mechanism causes inhibition of Ca2+ absorption. This report further shows that
      dexamethasone (DEX) rapidly enhanced calbindin-D28K gene expression, that is de
      novo calbindin-D28K mRNA biosynthesis. DEX also markedly reduced the actions of
      RNA and protein synthesis inhibitors on calbindin-D28K gene expression, although
      no evidence for an action of DEX or 1,25-(OH)2D3 at the translational level was
      obtained. Ca2+ transport activity was highly correlated with calbindin-D28K
      concentration regardless of treatment. Washout permitted complete reversal of
      inhibition, verifying the specificity of inhibitor activity. These results appear
      to show positive contranscriptional regulation of calbindin-D28K gene expression
      by 1,25-(OH)2D3 and glucocorticoids. The use of this model should continue to
      clarify the interactive roles of nuclear-acting hormones on the Ca2+ absorptive
      mechanism and on complex physiological and pathological processes in general.

PMID- 1989873
TI  - Thymosin gene expression is modulated by pregnant mare's serum gonadotropin,
      human chorionic gonadotropin, and prostaglandin F2 alpha in the immature rat
      ovary.
AB  - We have investigated thymosin beta 10 mRNA levels in the PMSG/hCG-treated
      immature rat ovary. Thymosin beta 10 mRNA was constitutively expressed as a
      single (greater than 600-nucleotide) abundant transcript in the immature rat
      ovary. Administration of a single dose (50 IU/rat) of PMSG to immature rats
      resulted in a gradual increase in steady state ovarian thymosin beta 10 mRNA
      content detectable as early as 12 h and maximal (2-to 3-fold stimulation above
      preinjection levels) 48 h after PMSG treatment. Ovarian thymosin beta 10 mRNA
      levels declined thereafter. In separate experiments treatment of PMSG (50 IU)
      primed rats with hCG (25 IU) precipitated a dramatic (80%) inhibition of ambient
      ovarian thymosin beta 10 protein and thymosin beta 10 mRNA; both parameters
      remained suppressed for the duration of the hormone-induced pseudopregnancy (15
      days). HPLC analysis also indicated the presence in the ovary of thymosin beta 4,
      a variant member of the same protein family; in general, ovarian thymosin beta 4
      levels fluctuated in a manner reciprocal to that exhibited by thymosin beta 10. A
      luteolytic dose of prostaglandin F2 alpha (500 micrograms/rat) had little impact
      on ovarian thymosin beta 10 gene expression. These findings show that 1) PMSG
      stimulation of ovarian thymosin beta 10 biosynthesis involves increased
      expression of the thymosin beta 10 gene; 2) decreased expression of thymosin beta
      10 is associated with luteinization, while increased thymosin beta 4 levels
      characterize this process; and that 3) thymosin beta 4 and beta 10 are
      coexpressed in this tissue and may play a significant but, as of yet, undefined
      role(s) in the ovary.

PMID- 1989874
TI  - Pulsatile luteinizing hormone secretion in normal female mice and in hypogonadal
      female mice with preoptic area implants.
AB  - Pulsatile LH secretion is driven by GnRH, the hypothalamic hormone that is
      lacking in the hypogonadal mutant mouse. Preoptic area grafts containing GnRH
      neurons correct many reproductive deficits in hypogonadal mice. In this study we
      evaluated the pattern of LH secretion in hypogonadal female mice with preoptic
      area grafts (hpg/POA) and in normal female mice. Normal females were
      ovariectomized at 10 weeks of age, and hpg/POA mice were ovariectomized 4 months
      after graft surgery. Three weeks later, all mice received intracardial catheters.
      The next day, sequential blood samples were obtained every 10 min for 4 h from
      the awake, freely moving mice. At ovariectomy, normal and hpg/POA ovarian weights
      were 8.6 +/- 0.9 and 7.1 +/- 1.2 mg, respectively. Significant LH pulses were
      detected in 9 of 10 normal mice and in 9 of 13 hpg/POA mice. Pulse frequency
      (normal, 0.86 +/- 0.13; hpg/POA, 0.61 +/- 0.13 pulse/h) and interpeak interval
      (normal, 81.7 +/- 20.3; hpg/POA, 93.2 +/- 24.0 min) were not significantly
      different (P greater than 0.2), but mean plasma LH levels (normal, 1.07 +/- 0.16
      ng/ml; hpg/POA, 0.49 +/- 0.08 ng/ml; P less than 0.005) and mean LH pulse
      amplitude (normal, 1.92 +/- 0.53; hpg/POA, 0.63 +/- 0.28; P less than 0.05) were
      significantly lower in the hpg/POA mice. The lower mean LH level and LH pulse
      amplitude in ovariectomized hpg/POA mice are consistent with the inability of
      most of these mice to show increased LH secretion after castration. The findings
      indicate that preoptic area brain grafts are capable of supporting episodic LH
      release in the hypogonadal mouse and suggest the presence of a functional GnRH
      pulse generator in the majority of mice with grafts.

PMID- 1989876
TI  - Role of secretin in basal and fat-stimulated pancreatic secretion in conscious
      rats.
AB  - The role of endogenous secretin in basal and fat-stimulated pancreatic exocrine
      secretion was investigated in conscious rats. Rats were prepared with chronic
      fistulas draining bile and pancreatic juice, which was collected and returned to
      the duodenum at all times. Six days postoperative rats were fasted overnight, and
      pancreatic protein and fluid secretion were monitored for 3 h under basal
      conditions (0.15 M NaCl, intraduodenally) and during 2 h of intraduodenal
      infusion of a 20% triglyceride emulsion (Liposyn). Solutions were infused at 4.6
      ml/h. Rats received a single bolus injection of 0.1 ml antisecretin serum or
      normal rabbit serum starting in the second hour of the basal period, and the
      effect on basal and fat-stimulated pancreatic protein and fluid secretion was
      determined. Antisecretin serum significantly inhibited basal interdigestive
      pancreatic protein and fluid secretion by 43% and 36%, respectively. Infusion of
      20% fat emulsion stimulated a 2.1-fold increase in pancreatic protein and fluid
      secretion. The stimulation of both protein and fluid secretion was significantly
      inhibited by 60% by antisecretin serum. Plasma secretin after 2 h of fat infusion
      was 17.7 +/- 1.8 pM and was greatly reduced by the presence of secretin
      antiserum. The results support the hypothesis that secretin released by fatty
      acids is an important mediator of the pancreatic protein and fluid secretory
      response to dietary fat in the rat.

PMID- 1989875
TI  - Regulation of gene expression in choriocarcinoma by methotrexate and hydroxyurea.
AB  - Choriocarcinoma, a highly malignant neoplasm of trophoblastic origin, is
      remarkable for its marked degree of sensitivity to chemotherapeutic agents. We
      treated two cell lines derived from choriocarcinoma patients with two
      antineoplastic agents, methotrexate and hydroxyurea (HU), both of which cause
      nucleotide depletion and have been previously shown to be effective against
      choriocarcinoma, and found pleiotropic regulation of several genes. Three genes,
      hCG alpha-subunit, beta-subunit, and placental alkaline phosphatase, were all
      strongly induced by methotrexate and HU. Expression of c-myc, an oncogene
      associated with proliferation, was reduced to nearly undetectable levels by the
      drug treatment, while expression of beta 2-microglobulin, a component of the
      class 1 major histocompatibility locus, was unchanged. In addition, the mechanism
      of induction by HU of one of these genes, the hCG alpha-subunit gene, was found
      to occur at the level of transcription. The similar effects of methotrexate and
      HU, two mechanistically unrelated antimetabolites, on the induction of specific
      gene expression in choriocarcinoma cells suggest that these effects are due to
      nucleotide pool alteration, rather than specific ligand effects. Furthermore, the
      hCG alpha-subunit promoter contains a transcriptionally regulated HU-responsive
      element.

PMID- 1989877
TI  - Ontogeny of corticosteroid-binding globulin biosynthesis in the rat.
AB  - In plasma, glucocorticoids are transported by corticosteroid-binding globulin
      (CBG), which is synthesized primarily in the liver. Plasma levels of maternal and
      fetal CBG fluctuate during gestation, and this may be due to changes in the
      biosynthesis and/or clearance of the protein. We have, therefore, studied the
      ontogeny of CBG biosynthesis in the rat by using a solution hybridization assay
      to measure hepatic CBG mRNA levels. The results indicate that the concentration
      of CBG mRNA is exceptionally high in 15-day-old fetal livers (55.1 pg CBG
      mRNA/micrograms total RNA), but declines to very low levels at birth (day 21).
      During the same period, CBG mRNA levels in maternal livers remained relatively
      constant (18.9-23.1 pg CBG mRNA/micrograms total RNA). Hepatic CBG mRNA levels
      were barely detectable 1 week after birth, and a sex difference was apparent by 2
      weeks of age, with higher levels in female livers. Although adult CBG mRNA levels
      were attained by 3 weeks of age, serum CBG concentrations did not reach adult
      values for an additional 3 weeks. To determine whether age-related differences in
      the clearance of CBG are responsible for this, CBG from infant or adult animals
      was radiolabeled and administered iv to infant and adult rats. When this was
      done, the half-life of CBG in infants (approximately 6.9 h) was consistently less
      than that in adults (approximately 14.5 h) regardless of the source of the
      labeled CBG, and we conclude that variations in CBG biosynthesis and clearance
      may influence glucocorticoid action during fetal and postnatal development.

PMID- 1989878
TI  - Three-dimensional structure of porcine procarboxypeptidase B: a structural basis
      of its inactivity.
AB  - Procarboxypeptidase B is converted to enzymatically active carboxypeptidase B by
      limited proteolysis catalysed by trypsin, removing the long N-terminal activation
      segment of 95 amino acids. The three-dimensional crystal structure of
      procarboxypeptidase B from porcine pancreas has been determined at 2.3 A
      resolution and refined to a crystallographic R-factor of 0.169. The functional
      determinants of its enzymatic inactivity and of its activation by limited
      proteolysis have thus been unveiled. The activation segment folds in a globular
      region with an open sandwich antiparallel-alpha antiparallel-beta topology and in
      a C terminal alpha-helix which connects it to the enzyme moiety. The globular
      region (A7-A82) shields the preformed active site, and establishes specific
      interactions with residues important for substrate recognition. AspA41 forms a
      salt bridge with Arg145, which in active carboxypeptidase binds the C-terminal
      carboxyl group of substrate molecules. The connecting region occupies the
      putative extended substrate binding site. The scissile peptide bond cleaved by
      trypsin during activation is very exposed. Its cleavage leads to the release of
      the activation segment and to exposure of the substrate binding site. An open
      sandwich folding has been observed in a number of other proteins and protein
      domains. One of them is the C-terminal fragment of L7/L12, a ribosomal protein
      from Escherichia coli that displays a topology similar to the activation domain
      of procarboxypeptidase.

PMID- 1989879
TI  - The NMR structure of the activation domain isolated from porcine
      procarboxypeptidase B.
AB  - The three-dimensional structure of the activation domain isolated from porcine
      pancreatic procarboxypeptidase B was determined using 1H NMR spectroscopy. A
      group of 20 conformers is used to describe the solution structure of this 81
      residue polypeptide chain, which has a well-defined backbone fold from residues
      11-76 with an average root mean square distance for the backbone atoms of 1.0 +/-
      0.1 A relative to the mean of the 20 conformers. The molecular architecture
      contains a four-stranded beta-sheet with the polypeptide segments 11-17, 36-39,
      50-56 and 75-76, two well defined alpha-helices from residues 20-30 and 60-70,
      and a 3(10) helix from residues 43-46. The three helices are oriented almost
      exactly antiparallel to each other, are all on the same side of the beta-sheet,
      and the helix axes from an angle of approximately 45 degrees relative to the
      direction of the beta-strands. Three segments linking beta-strands and helical
      secondary structures, with residues 32-35, 39-43 and 56-61, are significantly
      less well ordered than the rest of the molecule. In the three-dimensional
      structure two of these loops (residues 32-35 and 56-61) are located close to each
      other near the protein surface, forming a continuous region of increased
      mobility, and the third disordered loop is separated from this region only by the
      peripheral beta-strand 36-39 and precedes the short 3(10) helix.

PMID- 1989880
TI  - Identification and cloning of TCF-1, a T lymphocyte-specific transcription factor
      containing a sequence-specific HMG box.
AB  - CD3-epsilon expression is controlled by a downstream T lymphocyte-specific
      enhancer element. We report the identification of a T cell-specific transcription
      factor, TCF-1, binding to this element. The multimerized recognition motif of TCF
      1 constituted a T cell-specific enhancer. Subsequent cloning of TCF-1 identified
      three splice alternatives. TCF-1 contained a single DNA-binding HMG box most
      closely related to similar boxes in the putative mammalian sex-determining gene
      SRY and in the Schizosaccharomyces pombe Mc mating type gene. TCF-1 mRNA was
      expressed uniquely in T lymphocytes. Upon cotransfection into non-T cells, TCF-1
      could transactivate through its cognate motif. These results identify TCF-1 as a
      T cell-specific transcription factor, which might play a role in the
      establishment of the mature T cell phenotype.

PMID- 1989881
TI  - The MYC protein activates transcription of the alpha-prothymosin gene.
AB  - The proto-oncogene MYC encodes a nuclear protein whose biochemical and
      physiological functions remain uncertain. We used an estrogen-regulated version
      of the MYC protein to explore these functions. Activation of MYC in quiescent rat
      and mouse fibroblasts elicited re-entry into and progression through the cell
      cycle, bypassing early events that would follow stimulation of the cells with
      serum. Activation of MYC led to a rapid increase in transcription of the alpha
      prothymosin gene, even in the absence of protein synthesis. We conclude that the
      product of MYC acts directly on transcription, in accord with inferences based on
      the structure of the MYC protein. The function of alpha-prothymosin is not known,
      but our results suggest that the protein may play a role in the proliferation of
      mammalian cells.

PMID- 1989882
TI  - The 3'-5' exonuclease of DNA polymerase I of Escherichia coli: contribution of
      each amino acid at the active site to the reaction.
AB  - We have used site-directed mutagenesis to change amino acid side chains that have
      been shown crystallographically to be in close proximity to a DNA 3' terminus
      bound at the 3'-5' exonuclease active site of Klenow fragment. Exonuclease assays
      of the resulting mutant proteins indicate that the largest effects on exonuclease
      activity result from mutations in a group of carboxylate side chains (Asp355,
      Asp424 and Asp501) anchoring two divalent metal ions that are essential for
      exonuclease activity. Another carboxylate (Glu357) within this cluster seems to
      be less important as a metal ligand, but may play a separate role in catalysis of
      the exonuclease reaction. A second group of residues (Leu361, Phe473 and Tyr497),
      located around the terminal base and ribose positions, plays a secondary role,
      ensuring correct positioning of the substrate in the active site and perhaps also
      facilitating melting of a duplex DNA substrate by interacting with the frayed 3'
      terminus. The pH-dependence of the 3'-5' exonuclease reaction is consistent with
      a mechanism in which nucleophilic attack on the terminal phosphodiester bond is
      initiated by a hydroxide ion coordinated to one of the enzyme-bound metal ions.

PMID- 1989883
TI  - The new gene mukB codes for a 177 kd protein with coiled-coil domains involved in
      chromosome partitioning of E. coli.
AB  - An Escherichia coli temperature sensitive mutant which produces spontaneously
      normal size anucleate cells at low temperature was isolated. The mutant is
      defective in a previously undescribed gene, named mukB, located at 21 min on the
      chromosome. The mukB gene codes for a large protein (approximately 180 kd). A
      1534 amino acid protein (176,826 daltons) was deduced from the nucleotide
      sequence of the mukB gene. Computer analysis revealed that the predicted MukB
      protein has distinct domains: an amino-terminal globular domain containing a
      nucleotide binding sequence, a central region containing two alpha-helical coiled
      coil domains and one globular domain, and a carboxyl-terminal globular domain
      which is rich in Cys, Arg and Lys. A 180 kd protein detected in wild-type cell
      extracts by electrophoresis is absent in mukB null mutants. Although the null
      mutants are not lethal at low temperature, the absence of MukB leads to aberrant
      chromosome partitioning. At high temperature the mukB null mutants cannot form
      colonies and many nucleoids are distributed irregularly along elongated cells. We
      conclude that the MukB protein is required for chromosome partitioning in E.
      coli.

PMID- 1989884
TI  - S. pombe pac1+, whose overexpression inhibits sexual development, encodes a
      ribonuclease III-like RNase.
AB  - The Schizosaccharomyces pombe pac1 gene is a multicopy suppressor of the pat1
      temperature-sensitive mutation, which directs uncontrolled meiosis at the
      restrictive temperature. Overexpression of the pac1 gene had no apparent effect
      on vegetative growth but inhibited mating and sporulation in wild type S. pombe
      cells. In such cells, expression of certain genes required for mating or meiosis
      was inhibited. The pac1 gene is essential for vegetative cell growth. The deduced
      pac1 gene product has 363 amino acids. Its C-terminal 230 residues revealed 25%
      amino acid identity with ribonuclease III, an enzyme that digests double-stranded
      RNA and is involved in processing ribosomal RNA precursors and certain mRNAs in
      Escherichia coli. The pac1 gene product could degrade double-stranded RNA in
      vitro. These observations establish the presence of a RNase III homolog in
      eukaryotic cells. The pac1 gene product probably inhibits mating and meiosis by
      degrading a specific mRNA(s) required for sexual development. It is likely that
      mRNA processing is involved in the regulation of sexual development in fission
      yeast.

PMID- 1989886
TI  - Structural basis for the 3'-5' exonuclease activity of Escherichia coli DNA
      polymerase I: a two metal ion mechanism.
AB  - The refined crystal structures of the large proteolytic fragment (Klenow
      fragment) of Escherichia coli DNA polymerase I and its complexes with a
      deoxynucleoside monophosphate product and a single-stranded DNA substrate offer a
      detailed picture of an editing 3'-5' exonuclease active site. The structures of
      these complexes have been refined to R-factors of 0.18 and 0.19 at 2.6 and 3.1 A
      resolution respectively. The complex with a thymidine tetranucleotide complex
      shows numerous hydrophobic and hydrogen-bonding interactions between the protein
      and an extended tetranucleotide that account for the ability of this enzyme to
      denature four nucleotides at the 3' end of duplex DNA. The structures of these
      complexes provide details that support and extend a proposed two metal ion
      mechanism for the 3'-5' editing exonuclease reaction that may be general for a
      large family of phosphoryltransfer enzymes. A nucleophilic attack on the
      phosphorous atom of the terminal nucleotide is postulated to be carried out by a
      hydroxide ion that is activated by one divalent metal, while the expected
      pentacoordinate transition state and the leaving oxyanion are stabilized by a
      second divalent metal ion that is 3.9 A from the first. Virtually all aspects of
      the pretransition state substrate complex are directly seen in the structures,
      and only very small changes in the positions of phosphate atoms are required to
      form the transition state.

PMID- 1989885
TI  - UBA 1: an essential yeast gene encoding ubiquitin-activating enzyme.
AB  - All known functions of ubiquitin are mediated through its covalent attachment to
      other proteins. The post-translational formation of ubiquitin--protein conjugates
      is preceded by an ATP-requiring step in which the carboxyl terminus of ubiquitin
      is adenylated and subsequently joined, through a thiolester bond, to a cysteine
      residue in the ubiquitin-activating enzyme, also known as E1. We report the
      isolation and functional analysis of the gene (UBA1) for the ubiquitin-activating
      enzyme of the yeast Saccharomyces cerevisiae. UBA1 encodes a 114 kd protein whose
      amino acid sequence contains motifs characteristic of nucleotide-binding sites.
      Expression of catalytically active UBA1 protein in E. coli, which lacks the
      ubiquitin system, confirmed that the yeast UBA1 gene encodes a ubiquitin
      activating enzyme. Deletion of the UBA1 gene is lethal, demonstrating that the
      formation of ubiquitin--protein conjugates is essential for cell viability.

PMID- 1989889
TI  - The network.

PMID- 1989887
TI  - The conformation of a B-DNA decamer is mainly determined by its sequence and not
      by crystal environment.
AB  - By comparing the conformations adopted by a double-stranded decameric B-DNA
      fragment in different crystal environments, we address the question of the degree
      of deformability of DNA helices. The three-dimensional structure of the self
      complementary DNA decamer CCAGGCmeCTGG has been determined from crystals of space
      group P6 at 2.25 A resolution with an R value of 17.2% for 2407 1 sigma structure
      amplitudes. The oligonucleotide forms a B-type double helix with a characteristic
      sequence-dependent conformation closely resembling that of the corresponding
      unmethylated decamer, the structure of which is known from a high-resolution
      analysis of crystals of space group C2. Evidently, both the effects of single
      site methylation and altered crystal environment on the DNA conformation are
      small. Therefore, double-helical DNA may possess sequence-determined
      conformational features that are less deformable than previously thought.

PMID- 1989888
TI  - Regulated expression and structure of T cell receptor gamma/delta transcripts in
      human thymic ontogeny.
AB  - Gamma delta (gamma delta) T cells have been found in all vertebrates examined,
      yet their function in vivo remains unknown. Because gamma delta T cell receptors
      are related to immunoglobulin, and because they are encoded by rearranging, multi
      gene families, the receptors are thought to be antigen recognition molecules.
      However, a capacity to recognize naturally diverse antigens has not yet been
      shown. In this work, the expression and structure of human gamma delta
      transcripts have been examined in the fetal and early post-natal thymus. The data
      indicate that many gamma and delta genes are rearranged and expressed throughout
      ontogeny, but that as ontogeny proceeds, quite dramatic changes occur in the
      patterns of gene expression and rearrangement. In particular, receptors encoded
      by early to mid-gestation fetal thymic transcripts would be of quite restricted
      diversity. Only later in ontogeny can receptors of substantial diversity be
      generated. These properties are very similar to the patterns of gamma delta gene
      activation in the mouse, and they serve to reiterate similarities both in gene
      rearrangement and in gamma delta across vertebrate species.

PMID- 1989890
TI  - Expression of interleukin 6 and its specific receptor by untreated and PMA
      stimulated human erythroid and megakaryocytic cell lines.
AB  - Different human hematopoietic cell lines were analyzed for the presence of
      interleukin 6 (IL-6) and IL-6 receptor (IL-6-R). Both IL-6 mRNA and secreted
      active IL-6 protein were detectable in untreated cell lines with erythroid or
      megakaryoblastic features (K562, HEL, KU 812, MEG-01, and Dami), but they were
      not expressed constitutively in other leukemic cell lines (KG1, HL60, and U937).
      IL-6-R production, studied by the presence of its mRNA and specific binding sites
      for iodinated recombinant IL-6, was detected in most cell lines except K562, HEL,
      and Dami. Therefore, only KU 812 and MEG-01 coexpress both IL-6 and IL-6-R. After
      phorbol ester myristate acetate (PMA) treatment, all the cell lines studied
      expressed or overexpressed IL-6. In the erythroid K562 cell line, IL-6-R was not
      detectable before induction, but was promptly expressed after stimulation with
      PMA, suggesting that some of the new features of K562 cells induced by PMA may be
      mediated by IL-6. However, neutralizing antibodies against IL-6 did not block
      either the growth arrest or the loss of the erythroid phenotype induced by PMA.
      The presence of IL-6 and IL-6-R in erythroid and megakaryocytic leukemic cell
      lines suggests that their synthesis may occur during normal hematopoietic
      differentiation.

PMID- 1989891
TI  - Compensatory mechanisms in platelet production: the response of Sl/Sld mice to 5
      fluorouracil.
AB  - Sl/Sld mice are a unique animal model for studying platelet production in that
      they sustain normal platelet mass despite reduced marrow activity. The aim of
      this study was to determine if the compensatory mechanisms operating in these
      mice could be augmented by further reducing bone marrow activity with the drug 5
      fluorouracil (5-FU), known to induce a strong stimulatory effect on platelet
      production. The platelet recovery in Sl/Sld mice after 5-FU administration
      contrasted that found in their normal littermates. Sl/Sld mice did not display
      the sustained thrombocytosis that was observed in +/+ mice between days 10 and
      14. Platelet number was elevated in Sl/Sld mice at day 20, when the marrow
      megakaryocyte compartment had normalized. A significant increase in marrow
      megakaryocyte number and size was observed at days 8 and 11 in both +/+ and
      Sl/Sld mice after 5-FU administration. The data suggest that the increase in
      megakaryocyte size and number following 5-FU treatment was not able to
      significantly contribute to a sustained rebound thrombocytosis at the time of
      increased marrow megakaryocytopoiesis. It is concluded that the already
      compromised marrow of Sl/Sld mice is able to respond to the damage invoked by 5
      FU to produce larger than normal megakaryocytes. In contrast to normal mice (+/+
      littermates), the increase in marrow megakaryocytopoiesis observed does not lead
      to a thrombocytosis, indicating that platelet production and release in Sl/Sld
      mice cannot be further amplified by a strong marrow stimulation.

PMID- 1989892
TI  - The erythropoietic effects of interleukin 6 and erythropoietin in vivo.
AB  - The purpose of this investigation was to compare the erythropoietic effects of
      recombinant interleukin 6 (IL-6) and recombinant erythropoietin (EPO) on the
      marrow and peripheral blood in vivo. IL-6 administered to rats as a single i.v.
      injection induces a selective erythroid hyperplasia of the marrow's late
      normoblasts at 12 and 24 h with a return to preinjection numbers of normoblasts
      at 48 and 72 h. The hyperplasia of late normoblasts in the marrow is accompanied
      by a left-shifted peripheral reticulocytosis. Daily injection of IL-6 does not
      induce any effects on the erythroid population of the marrow or circulation
      beyond those of a single injection. After daily administration of IL-6 for 4 or 7
      days, the erythroid differential in the marrow and the peripheral reticulocyte
      count are equal to negative control values, indicating a rapid tachyphylaxis to
      the erythropoietic effect of IL-6. In contrast to IL-6, EPO administered as a
      single i.v. injection induces a panerythroid marrow hyperplasia with sequential
      peak increases in pronormoblasts and early normoblasts at 24 h, intermediate
      normoblasts at 24-48 h, and late normoblasts at 72 h. The peripheral reticulocyte
      count mirrors the development of erythroid precursors in the marrow by
      demonstrating an increasing left-shifted reticulocytosis between 24 and 72 h.
      Daily injection of EPO for 7 days induces a striking erythroid hyperplasia and a
      myeloid hypoplasia in the marrow. In summary, IL-6 in vivo is a differentiation
      factor that rapidly induces tolerance to its own effect, whereas EPO in vivo
      affects all stages of erythropoiesis and sustains erythropoiesis indefinitely. IL
      6 may be one of the non-EPO factors in pokeweed mitogen spleen cell-conditioned
      medium that has been reported by previous investigators to enhance
      erythropoiesis, although many of those factors were thought to act upon an
      earlier stage of erythropoiesis. IL-6 is unlikely to exert an indirect
      erythropoietic effect in vivo via the induction of EPO because the sera of IL-6
      treated rats did not contain elevated levels of EPO and because the effects of
      exogenously administered IL-6 and EPO are so different.

PMID- 1989893
TI  - In vitro differentiation and proliferation of human hematopoietic progenitors:
      the effects of interleukins 1 and 6 are indirectly mediated by production of
      granulocyte-macrophage colony-stimulating factor and interleukin 3.
AB  - The effect of recombinant human interleukin (IL)-1 and IL-6 on the
      differentiation and proliferation in vitro of human granulocyte-macrophage (GM)
      and erythroid progenitors has been investigated in either fetal bovine serum
      (FBS)-supplemented or FBS-deprived cultures. Sources of progenitor cells were
      unfractionated bone marrow cells or marrow cells depleted of adherent and/or T
      cells. Each interleukin was investigated either alone or in combination with GM
      colony-stimulating factor (CSF), IL-3 and erythropoietin (Epo), or granulocyte
      (G)-CSF. In FBS-supplemented cultures of unfractionated marrow cells, IL-1
      induced optimal GM colony growth and increased by 50% the number of erythroid
      bursts that formed in the presence of Epo. The addition to these cultures of a
      neutralizing anti-GM-CSF monoclonal antibody or of an anti-IL-3 serum decreased
      the growth of GM colonies by 80% and 40%, respectively. Under the same
      conditions, IL-6 had no effect on GM colony growth but increased by 90% the
      number of erythroid bursts. This effect was partially (40%) neutralized by
      addition of anti-IL-3 serum. IL-1 and IL-6 were weak stimuli, or had no effect at
      all, either alone or in combination with GM-CSF and IL-3 in FBS-deprived cultures
      or in FBS-supplemented cultures of nonadherent or nonadherent, T-cell-depleted
      marrow cells. IL-1 and IL-6 had no effect, either alone or in combination with IL
      3, in maintaining the number of progenitor cells in short-term liquid suspension
      cultures. These results indicate that the actions of IL-1 and IL-6 on
      hematopoiesis are mainly indirect and mediated by the production of GM-CSF and/or
      IL-3 by accessory cells. However, neither IL-1 nor IL-6 alone is sufficient to
      stimulate production of growth factor(s) by accessory cells, and at least a
      second stimulus, provided by FBS, is also required. These data are in agreement
      with a multisignal model of regulation of the expression of growth factor genes.

PMID- 1989894
TI  - Canine megakaryocytopoiesis: analysis utilizing a monoclonal antibody to a 140-kd
      dog platelet protein.
AB  - The dog, a convenient and relatively large animal whose size permits repetitive
      blood and marrow sampling, marrow biopsy, and mechanical apheresis, would be a
      suitable experimental model for the study of in vivo megakaryocytopoiesis. A
      monoclonal antibody to a 140-kd dog platelet membrane protein has been developed
      that reacts with canine megakaryocytes. Using the fluoresceinated derivative of
      this antibody to identify megakaryocytes and propidium iodide staining to measure
      relative DNA content, the DNA distribution of megakaryocytes in dog bone marrow
      or in cultured dog marrow cells could be rapidly assessed by flow cytometry.
      Normal dogs showed a modal ploidy of 16N (54%), with 17% 8N and 16% 32N. In
      contrast, dogs made thrombocytopenic by plateletpheresis showed a shift in
      distribution to higher ploidy cells (36% 32N). The data show that use of a
      specific marker of megakaryocytes in combination with flow cytometric analysis is
      an accurate and reproducible method of assessing megakaryocytopoiesis in a
      convenient and easily manipulable animal model.

PMID- 1989895
TI  - Hematopoietic factor-induced synthesis of von Willebrand factor by the Dami human
      megakaryoblastic cell line and by normal human megakaryocytes.
AB  - Identification of hemopoietic factors and the molecular mechanisms by which they
      regulate the various stages of megakaryocyte development and platelet protein
      expression has been hampered by the lack of a purified, self-renewing, and
      responsive biological assay system. Previously, the human megakaryocytic Dami
      cell line has been shown to differentiate in response to phorbol ester by
      increasing the expression of platelet membrane glycoproteins Ib, IIb/IIIa, and
      the platelet protein, von Willebrand Factor (vWF). In this report, we demonstrate
      that this cell line is a suitable model for investigating the effects of specific
      cytokines and hemopoietic factors on the terminal differentiation of
      megakaryocytes as measured by the stimulated biosynthesis of vWF in serum-free
      culture. Although a low concentration (10 U/ml) of purified recombinant
      interleukin 3 (IL-3) had no effect, a higher concentration (100 U/ml) stimulated
      a three- to four fold increase in vWF synthesis. Purified thrombopoiesis
      stimulating factor (TSF) alone induced a two- to threefold increase, and when
      used in combination with 10 U/ml IL-3, TSF induced a synergistic five- to sixfold
      increase in vWF synthesis. Recombinant erythropoietin (EPO) and human interleukin
      6 (IL-6) each induced a twofold increase in vWF, and each acted additively with
      10 U/ml IL-3. IL-3 and TSF stimulated similar increases in vWF expression by
      human megakaryocytes contained in nonadherent bone marrow preparations. These
      results demonstrate the usefulness of the Dami cell line as a serum-free culture
      system in which to study the direct effects of purified humoral factors on
      megakaryocyte and platelet protein synthesis during megakaryocyte maturation.

PMID- 1989896
TI  - Expression of mRNAs in human thymus coding for the alpha 3 subunit of a neuronal
      acetylcholine receptor.
AB  - We report the isolation of clones from a human thymus cDNA library that code for
      the alpha 3 subunit of a neuronal acetylcholine receptor (AcChR). The clones
      hybridize to one major 3.0-kb mRNA thymic species and four minor ones of
      approximately 2.3, 4.0, 5.0, and 6.5 kb, but they do not hybridize to human
      muscle mRNA. These clones may be of value in defining the cholinergic thymic
      makeup and the putative role that a thymic AcChR may have in the triggering
      and/or maintenance of an anti-AcChR response in the autoimmune condition
      myasthenia gravis.

PMID- 1989897
TI  - A novel protein induced in cortical epileptic focus of rat cerebrum: a possible
      linkage to epileptogenesis.
AB  - To precisely evaluate a protein-related mechanism of epileptogenesis, we
      quantitatively analyzed the 70-kDa protein (namely, P70), a specific protein
      found in the cobalt-induced epileptic focus, and examined its effect on the
      electrocorticogram (ECoG) and cortical neurons in cerebral slices and its
      immunocytochemical localization in rats. Cobalt-induced cortical epileptogenic
      cortex exhibited a marked induction of P70. Its initiation time was ahead of the
      generation of epileptogenic activities. The anticonvulsant phenytoin (PHT)
      attenuated the cobalt-induced epileptogenic activities, but failed to suppress
      protein induction. Injection of this protein into the motor region of normal rat
      cerebral cortex elicited an epileptic ECoG and behavioral seizures. It also
      caused epileptiform activity with paroxysmal depolarization shifts in cortical
      neurons. These epileptogenic phenomena elicited by P70 were abolished by prior
      treatment with PHT or phenobarbital. Immunocytochemical analysis with an
      antiserum against P70 revealed that the reactivity was confined to pyramidal
      cells only in the region of the focus and was mainly localized on somatic,
      dendritic, and nuclear membranes and microtubles. These findings suggest that P70
      may be linked to epileptogenesis.

PMID- 1989898
TI  - Capillary and mitochondrial support of neural plasticity in adult rat visual
      cortex.
AB  - Young adult rats (60 days old) were placed in complex environments (EC) or kept
      in individual cages (IC) for 10, 30, or 60 days. Previously reported findings in
      these same animals of synaptogenesis, decreased neuronal density, and increased
      cortical thickness in the EC animals demonstrated that cortical volume
      substantially expanded after 30 days. Such expansion would have spread apart
      existing capillaries and mitochondria, thereby diluting metabolic support.
      However, capillary spacing and mitochondrial volume fraction were maintained in
      these EC animals after 30 days, suggesting that new capillaries and mitochondria
      had infiltrated the tissue. Furthermore, many small vessels appeared after 10
      days of complex experience, followed by expansion in vessel size until vessels
      from rats in EC for 60 days were larger than those from rats in IC for 60 days.
      The findings of constant vessel spacing in the face of expanding tissue volume,
      along with a set of small vessels that subsequently increased in size, suggest
      that small-sized new vessels were introduced in EC cortex by 10 days but had not
      matured in size until after 30 days. The results indicate that young adult rats
      can generate new capillaries and mitochondria in response to increased metabolic
      demands, but in a less vigorous fashion than in previously described weanling
      animals.

PMID- 1989899
TI  - Direct observation in vitro of how neuroblasts migrate: medulla and
      cochleovestibular ganglion of the chick embryo.
AB  - The hypothesis that neuroblasts migrate in the nervous system by a locomotory
      process was tested experimentally. An in vitro preparation permitted direct
      observation of postmitotic cells migrating from the rhombic lip of the medulla
      and the anlage of the cochleovestibular ganglion. Cell locomotion was not seen.
      Instead migration was produced by elongation of a leading process, followed by
      translocation of the nucleus (perikaryal translocation). On the basis of
      comparisons with previous observations in situ, we propose that this represents a
      common mode of migration in the developing nervous system. Cell clusters were
      explanted from the rhombic lip at the developmental stage when they migrate from
      the ventricular zone to the acoustico-vestibular anlage in the medulla. Cells
      from the cochleovestibular ganglion were explanted after migration from the
      otocyst, but before ganglionic differentiation. Each neuroblast's migration route
      was formed by an elongating leading process ending in a growth cone. The growth
      cone attached to other cells and processes or ended freely on an acellular
      substrate. Nonneuronal cells usually migrated as has been described for
      fibroblasts, yet with some of the features of perikaryal translocation, but some
      nonneuronal precursor cells may migrate the way neuroblasts do. Neuroblasts did
      not migrate preferentially on the processes of nonneuronal cells, although the
      reverse could be observed. In fact a variety of interactions between migratory
      cells, neuronal and nonneuronal, were observed. The advantage of the experimental
      system described here is that one can observe cells migrating spontaneously at
      the times in development when they normally do so, while preserving the cellular
      populations present in situ.

PMID- 1989900
TI  - Quantitative assessment of phrenic nerve functional recovery mediated by the
      crossed phrenic reflex at various time intervals after spinal cord injury.
AB  - The present study was carried out to determine if augmentation of phrenic nerve
      activity during the crossed phrenic phenomenon temporally coincides with the
      morphological changes in the phrenic nucleus that we have observed in previous
      studies. This investigation consisted of two experiments in spinal cord
      hemisected young adult female Sprague-Dawley rats. Crossed phrenic activity was
      quantitatively assessed from the left phrenic nerve after bilateral vagotomy and
      sectioning of the right phrenic and accessory phrenic nerves. The first
      experiment involved serial recordings of crossed phrenic activity performed on
      each of 4 animals at hourly intervals ranging from 1 to 6 h after spinal cord
      hemisection. The second experiment consisted of single recordings from each of 24
      animals at one of the following time intervals after hemisection: 1/2, 1, 2, 4,
      12, and 24 h. Recording conditions were standardized at each recording session in
      both experiments by paralyzing the animals, regulating temperature and blood
      pressure, and controlling end tidal PCO2 with a volume ventilator. Crossed
      phrenic activity was induced by stopping the ventilator and quantitated by
      measuring the area under the integrated waveform of the largest respiratory
      burst. The results revealed a small, statistically insignificant increase in
      crossed phrenic activity at 1 h compared to the 30-min recordings. At 2 h there
      was a large, statistically significant increase in activity. Experiment one
      showed further increases from 3 to 6 h. The second experiment showed a smaller
      increase from 2 to 4 h and then maintained this level at 12 and 24 h.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1989901
TI  - Selective decrease of small sensory neurons in lumbar dorsal root ganglia labeled
      with horseradish peroxidase after ND:YAG laser irradiation of the tibial nerve in
      the rat.
AB  - Recent electrophysiological evidence indicates that Q-switched Nd:YAG laser
      irradiation might have selective effects on neural impulse transmission in small
      slow conducting sensory nerve fibers as compared to large diameter afferents. In
      an attempt to clarify the ultimate fate of sensory neurons after laser
      application to their peripheral axons, we have used horseradish peroxidase (HRP)
      as a cell marker to retrogradely label sensory neurons innervating the distal
      hindlimb in the rat. Pulsed Nd:YAG laser light was applied to the tibial nerve at
      pulse energies of 70 or 80 mJ/pulse for 5 min in experimental rats. Seven days
      later HRP was applied to the left (laser-treated) and to the contralateral
      (untreated) tibial nerve proximal to the site of laser irradiation. In control
      animals the numbers of HRP-labeled dorsal root ganglion cells were not
      significantly different between the right and the left side. In contrast, after
      previous laser irradiation labeling was always less on the laser-treated side
      (2183 +/- 513 cells, mean +/- SEM) as compared to the untreated side (3937 +/-
      225). Analysis of the dimensions of labeled cells suggested that the reduction of
      labeled cells on the laser-treated side was mainly due to a deficit in small
      sensory neurons. Since the conduction velocity of nerve fibers is related to the
      size of their somata, our histological data imply that laser light selectively
      affects retrograde transport mechanisms for HRP in slow conducting sensory nerve
      fibers.

PMID- 1989902
TI  - The effects of polyamines and polyamine inhibitors on rat sciatic and facial
      nerve regeneration.
AB  - The effects of exogenous polyamines and polyamine biosynthetic pathway inhibitors
      on regenerating nerves were examined in adult male rats following nerve
      transection and surgical repair. Several studies have demonstrated the efficacy
      of exogenous polyamines in promoting the functional recovery of peripheral nerves
      following crush or freeze injuries in the rat. In order to simulate clinical
      peripheral nerve surgery, we studied these effects after complete nerve
      transection and evaluated regeneration by counting axons. There was no
      statistical difference in axon number with and without polyamines and in the
      presence of inhibitors and inhibitors with end product addition. Our study
      suggests that the difference in recovery seen in previous studies is not mediated
      by a change in axon number.

PMID- 1989903
TI  - Expression of a cAMP receptor gene of Dictyostelium and evidence for a multigene
      family.
AB  - We have previously reported the cloning of cDNAs for a Dictyostelium cell-surface
      cAMP receptor that is a member of the family of G-protein-linked receptors. Here,
      we report the organization and the developmental expression of this cAMP receptor
      gene, designated CAR1. CAR1 is a single copy gene that contains two intervening
      sequences. CAR1 mRNA levels are low in growing cells, rise to peak expression at
      5-10 hr of development when the cAMP signaling system is maximally active, and
      decrease as development proceeds. At 5 hr the predominant mRNA species is
      approximately 1.9 kb, by 10 hr the mRNA is heterogeneous with sizes of
      approximately 1.9-2.1 kb, but during culmination only the 2.1 kb mRNA is
      detected. The variety of mRNA sizes results from differences in 5'-untranslated
      regions. Studies using developmental mutants with aberrant cAMP-signaling
      patterns indicate that pulsatile action of cAMP promotes maximal expression of
      CAR1 during early development. Low stringency hybridization of CAR1 probes to
      genomic DNA detects additional, related sequences, suggesting that there are
      several genes that encode a family of structurally similar receptors. Multiple
      functions previously attributed to the cAMP receptor instead may be fulfilled by
      distinct receptor subtypes encoded by specific genes.

PMID- 1989904
TI  - Transcription factor AP-2 is expressed in neural crest cell lineages during mouse
      embryogenesis.
AB  - We have analyzed the expression pattern of transcription factor AP-2 in mouse
      embryos to evaluate the potential of AP-2 as a regulator during vertebrate
      development. A partial cDNA encoding AP-2 was isolated from a mouse embryo cDNA
      library and used to prepare probes to measure AP-2 mRNA levels by RNase
      protection and RNA in situ hybridization. Between 10.5 and 15.5 days of
      embryogenesis, the relative abundance of AP-2 mRNA is greatest at 11.5 days and
      declines steadily thereafter. RNA in situ hybridization analysis of embryos
      between 8.5 and 12.5 days of gestation identified a novel expression pattern for
      AP-2. The principle part of this expression occurs in neural crest cells and
      their major derivatives, including cranial and spinal sensory ganglia and facial
      mesenchyme. AP-2 is also expressed in surface ectoderm and in a longitudinal
      column of the spinal cord and hindbrain that is contacted by neural crest-derived
      sensory ganglia. Additional expression of AP-2 occurs in limb bud mesenchyme and
      in meso-metanephric regions. This embryonic expression pattern is spatially and
      temporally consistent with a role for AP-2 in regulating transcription of genes
      involved in the morphogenesis of the peripheral nervous system, face, limbs,
      skin, and nephric tissues.

PMID- 1989905
TI  - Reversible inhibition of a thyroid-specific trans-acting factor by Ras.
AB  - Exposure of rat thyroid cells for 1 week to a temperature-sensitive variant of
      Kirsten murine sarcoma virus (KiMSV) Ras inactivated the thyroglobulin promoter
      (pTg). Cellular dedifferentiation was paralleled by the loss of the thyroid
      specific trans-acting factor, TgTF1, which binds to pTg. When Ras was denatured
      by shifting cells to 39 degrees C, TgTF1 binding and pTg function recovered
      rapidly without the synthesis of new protein. TgTF1 could be reactivated in vitro
      by treating nuclear extracts with protein kinase A. After 4 weeks of exposure to
      the oncogene, denaturation of Ras no longer restored TgTF1 binding or reactivated
      pTg. Incubation of nuclear extracts with protein kinase A likewise did not
      reactivate TgTF1. Cells chronically exposed to Ras did, however, yield
      differentiated clones after treatment with 5-azacytidine. We suggest that Ras
      induces dedifferentiation in two sequential steps: (1) Ras reduces PKA activity;
      TgTF1 (or an auxiliary protein) becomes dephosphorylated, and binding to pTg is
      abolished. (2) The effects of Ras become imprinted by methylation, possibly of
      the TgTF1 gene.

PMID- 1989906
TI  - A yeast protein that binds to vertebrate telomeres and conserved yeast telomeric
      junctions.
AB  - We have identified three yeast proteins that bind to poly(C.A)/poly(T.G) repeats
      characteristic of telomeric sequences from yeast to human. TBF alpha binds to the
      telomeric sequences of yeast, Tetrahymena, and vertebrates. In contrast, TBF beta
      binds only to yeast telomeric sequences. Also identified was RAP1, the
      transcriptional silencer protein, which binds to a sequence motif found in
      upstream activating sequences (UASs) of a number of genes; the sequence motif
      also occurs frequently in yeast telomeric sequences. Because poly(C.A)/poly(T.G)
      sequences from a wide range of organisms will serve as the primer for the in vivo
      extension of telomeres in yeast, TBF alpha is of particular interest. DNase I
      footprinting analysis indicated that TBF alpha binds to the junction between the
      subtelomeric X sequence and poly(C1-3A) in a cloned yeast telomere. Examination
      of the junctions of known X sequences indicated that they all contain one or more
      repeats of CCCTAA, a sequence that is repeated in vertebrate telomeres. Earlier,
      Murray et al. (1988) reported that heterologous telomeric sequences positioned as
      far as several hundred base pairs from the termini of linear molecules can allow
      the addition of yeast telomeric sequences from nontelomeric termini in vivo. A
      possible function for TBF alpha might be to serve as an anchoring protein for the
      yeast telomerase by binding to the conserved junction sequence at a distance from
      the terminus to allow addition of an irregular repeating sequence at the
      chromosome end.

PMID- 1989907
TI  - DNA-protein interaction at the replication termini of plasmid R6K.
AB  - Understanding the molecular mechanism of specific and polarized termination of
      DNA replication at a sequence-specific replication terminus requires detailed
      analyses of the interaction of terminator protein (ter) with specific DNA
      sequences (tau), constituting the replication terminus. Such analyses should
      provide the structural basis of the functional polarity of replication inhibition
      observed in vivo and in vitro at tau sites. With this objective in mind, we have
      purified the replication terminator protein of Escherichia coli to homogeneity
      and have analyzed the interaction of the protein with the replication termini of
      R6K, using chemical probes and by site-directed mutagenesis. The results show
      that one monomer of ter protein binds to a single tau site with an equilibrium
      dissociation constant of 5 x 10(-9) moles/liter. Furthermore, a combination of
      alkylation interference and protection, hydroxyradical footprinting, and site
      directed mutagenesis has revealed the phosphate groups and base residues of the
      tau core sequence that make contacts with ter protein and those residues that are
      important for both DNA-protein interaction and for termination of replication in
      vivo. The overall picture that emerges from these analyses reveals that ter forms
      an asymmetric complex with a tau sequence. Thus, the asymmetric ter-tau complex
      provides a structural basis for the functional polarity of the arrest of a moving
      replication fork at a tau site.

PMID- 1989908
TI  - Rapid in vivo footprinting technique identifies proteins bound to the TTR gene in
      the mouse liver.
AB  - In vivo examination of the occupancy of DNA elements that can regulate
      transcription is critical to reveal which proteins actually take part in
      establishing and maintaining gene expression. We describe a new genomic
      sequencing method involving the rapid purification of relevant DNA segments from
      the bulk of the genomic DNA using a biotinylated riboprobe. The purified
      sequences are revealed by a single primer extension using Taq DNA polymerase. We
      used this technique to study the promoter and the enhancer of mouse transthyretin
      (TTR), a gene highly expressed in the liver. Footprints showed high liver
      specific occupancy of some, but not all, of the DNA sites that had been
      identified as important for expression by transfection studies in hepatoma cells.
      In addition, several previously undetected sites were observed that bound
      proteins specifically in liver. These results suggest that not all demonstrable
      binding sites are involved in ongoing transcription and that in vivo studies may
      reveal additional and probably more relevant sites.

PMID- 1989910
TI  - Class II radical hysterectomy shows less morbidity and good treatment efficacy
      compared to class III.
AB  - Treatment of 102 patients with cancer of the cervix by class II and III radical
      hysterectomy was reviewed to compare the operative morbidity and efficacy of
      class II radical hysterectomy for select cases. Of the 102 patients, 21 had a
      class II hysterectomy, whereas 81 patients had a class III hysterectomy. The
      class II operation was performed for those subjects in whom invasive cancer
      beyond microinvasion could not be excluded after a cone biopsy. The mean age and
      weight of women having class II and III radical hysterectomies were nearly
      identical (41.1 and 40.6 years, respectively, and 66 and 65 kg, respectively).
      However, the mean operative time (3.8 and 4.7 hr, respectively; P = 0.001) and
      postoperative hospital stay (7.3 and 9.2 days, respectively; P = 0.001) were
      lower for class II than for class III hysterectomies. No fistulas or recurrent
      cancer developed following class II hysterectomy, and no patients had metastatic
      cancer in the nodes or parametrium. Among the 81 women undergoing class III
      hysterectomy, there were 3 fistulae and 3 recurrences. We conclude that the
      lesser morbidity, including shorter operative time and shorter postoperative
      hospital stay and excellent cancer control of the class II radical hysterectomy
      and lymphadenectomy, recommend the operation for selected early cancers of the
      cervix especially when a question concerning depth of invasion exists after cone
      biopsy.

PMID- 1989909
TI  - Chemotherapy-induced neutropenia and fever in patients receiving cisplatin-based
      chemotherapy for ovarian malignancy.
AB  - Fifty-six episodes of chemotherapy-induced neutropenia and fever occurred in
      forty-three patients receiving cisplatin-based combination chemotherapy for
      ovarian cancer. All patients were treated with broad-spectrum antibiotics
      including gentamicin. Twelve of fifty-six episodes were associated with positive
      cultures; in six patients a single organism was isolated, and the other six
      patients had polymicrobial infection. The mean duration of antibiotic therapy was
      6.5 days. One patient died of sepsis. Fifty-five episodes had a successful
      outcome. There was no antibiotic-related morbidity. Based on this review we
      recommend broad-spectrum antibiotic therapy for chemotherapy-induced neutropenia
      with fever. The regimen of gentamicin plus ticarcillin and clavulanic acid
      (ceftazidime for penicillin-allergic patients) is effective as initial therapy.
      Additional agents (i.e., vancomycin) may be necessary in culture-positive
      patients based on sensitivity testing of bacterial isolates. Gentamicin can be
      safely administered to patients receiving cisplatin-based chemotherapy without
      compromising ability to continue cisplatin therapy in subsequent treatment
      cycles.

PMID- 1989911
TI  - Invasive carcinoma after cone biopsy for cervical intraepithelial neoplasia.
AB  - A retrospective review of 578 patients with invasive cervical cancer identified 8
      patients with a history of one or more cone biopsies for treatment of cervical
      intraepithelial neoplasia. The cone biopsy and hysterectomy specimens were
      reviewed to identify factors predictive of the subsequent development of invasive
      cancer. The mean interval from cone biopsy to diagnosis of invasive carcinoma was
      6.7 years (range 1.5-16.5 years). High-grade intraepithelial neoplasia is a
      potentially invasive lesion. Adenocarcinoma in situ was identified as a high-risk
      lesion that may be inadequately treated by cone biopsy. Four patients developed
      invasive squamous cancer in spite of complete excision of the initial lesion.
      Patients who have high-grade intraepithelial neoplasia treated with cone biopsy
      require long-term follow-up, and conization may hamper the subsequent diagnosis
      of preinvasive lesions.

PMID- 1989912
TI  - Neutralizing effect of sodium thiosulfate on antitumor efficacy of cisplatin for
      human carcinoma xenografts in nude mice.
AB  - The present study was designed to examine the antitumor efficacy of combination
      chemotherapy with sodium thiosulfate (STS) and cis-diamminedichloroplatinum
      (CDDP) using a murine model. Xenograft tumors of the endometrial adenocarcinoma
      cell line responded well to intraperitoneal chemotherapy with CDDP in nude mice.
      However, addition of STS to CDDP treatment canceled the antitumor effect of CDDP.
      Such a finding was obtained in mice injected subcutaneously with STS even 72 hr
      after treatment with CDDP. On the other hand, alleviation of CDDP-induced side
      effects by administration of STS was not observed in mice treated by several
      modalities of combination chemotherapy with STS and CDDP. Thus, addition of STS
      to CDDP treatment reduced CDDP's antitumor efficacy with only minimal alleviation
      of side effects, suggesting that it would provide no benefit in patients treated
      with CDDP.

PMID- 1989913
TI  - Intestinal surgery performed on gynecologic cancer patients.
AB  - A retrospective review covering a 9-year period revealed 113 patients who
      underwent 157 major bowel procedures during 130 operations performed solely by
      gynecologic oncology surgeons. Forty-eight percent of the operations were done
      for tumor cytoreduction, and 33% were performed for a bowel obstruction. Other
      indications included colostomy closure, fistula repair, resection for multiple
      enterotomies, temporary diversions, repair of perforated bowel, treatment for
      severe proctosigmoiditis, management of ureteral stricture, treatment for vulvar
      necrosis, and resection of an incidental small bowel tumor. Of the 157
      procedures, 44% were colostomies, 32% were bowel resections with reanastomosis,
      9% were urinary conduits, 6% were intestinal bypass procedures, 5% were colostomy
      closures, and 4% were ileostomies. Postoperative complications occurred in 32% of
      the 130 operations. These included wound infection, death, sepsis, fistula
      formation, urinary tract infection, unexplained febrile morbidity, anastomotic
      leakage, stomal infarction, adult respiratory distress syndrome, bowel
      obstruction, deep venous thrombosis, and wound hematoma. Four of the eight deaths
      were due to tumor progression, three were from sepsis, and one was from adult
      respiratory distress syndrome. Of the 130 operations, 89 (68%) were associated
      with no complications. These data support the concept that gynecologic oncology
      surgeons are able to perform intestinal operations as therapy for gynecologic
      malignancies with acceptable complication rates. Since a thorough understanding
      of the natural history of the cancer, familiarity with alternative therapeutic
      options, and knowledge of the prognosis are important in making operative
      decisions, and since gynecologic oncologists are technically capable of
      performing operations on the small bowel and colon, referral of patients with a
      primary or recurrent gynecologic malignancy or with a subsequent intestinal
      complication after initial therapy should be directed to the gynecologic
      oncologist whenever possible.

PMID- 1989914
TI  - Prognostic significance of the extent of cervical involvement by endometrial
      cancer.
AB  - The prognostic significance of the extent of cervical involvement by endometrial
      cancer is impossible to determine from the literature because previous reports
      have included fractional dilatation and curettage for staging, preoperative
      radiotherapy, and surgical stage III and IV disease. Therefore, we reviewed and
      restaged according to the new FIGO system all patients with endometrial cancer
      from January 1981 to December 1989. Of 180 patients undergoing hysterectomy for
      endometrial cancer, 20 had surgical stage II disease. No patient received
      preoperative radiotherapy. None of 12 patients (0%) with stage IIA disease
      developed recurrence, while 5 of 8 (63%) with stage IIB disease recurred (P less
      than 0.01). All 5 recurrences were in extrapelvic sites. Endocervical stroma
      invasion appears to import a statistically significant worse prognosis than
      endometrial glandular involvement.

PMID- 1989915
TI  - Tumor growth fraction in cervical carcinoma.
AB  - Thirty-one cervical carcinomas have been studied immunohistochemically to
      determine tumor growth fraction by using the monoclonal antibody Ki-67, which
      reacts with a nuclear antigen expressed only by proliferating cells. The growth
      fraction of individual tumor is estimated as the percentage of stained nuclei in
      a population of 1000 tumor cells. There is a good correlation of the growth
      fraction measured by Ki-67 with mitotic index and high histological grade of
      cervical carcinoma. This study, together with that of D. C. Brown, D. Cole, K. C.
      Gatter, and D. Y. Mason [Brit. J. Cancer 57(2), 178-181 (1988)], shows the
      usefulness of Ki-67 in the evaluation of growth fraction in cervical carcinoma.

PMID- 1989916
TI  - Relationship between surgical-pathological risk factors and outcome in clinical
      stage I and II carcinoma of the endometrium: a Gynecologic Oncology Group study.
AB  - Between June 20, 1977 and February 5, 1983, the Gynecologic Oncology Group
      entered 1180 women with clinical stage I or II (occult) endometrial carcinoma
      into a surgical-pathological staging study. Eight hundred ninety-five patients
      with endometrioid or adenosquamous carcinoma were evaluable for this study which
      relates surgical-pathological parameters and postoperative treatment to
      recurrence-free interval and recurrence site. Proportional hazards modeling of
      time to recurrence was performed. For patients without metastasis determined by
      surgical-pathological staging the greatest determinant of recurrence was grade 3
      histology adenocarcinoma grade 3, relative risk (RR) = 15; adenosquamous
      carcinoma grade 3, RR = 8.1; all adenocanthomas, RR = 1.0). Of 48 patients with
      histologically documented aortic node metastases, 47 had one or more of the
      following features: (1) grossly positive pelvic nodes, (2) grossly positive
      adnexal metastasis, or (3) outer one-third myometrial invasion. Pelvic radiation
      was administered to 48.0% and vaginal brachytherapy alone to 10.2% of patients
      postoperatively; 41.8% received no adjuvant radiation therapy. None of three
      recurrences in the vaginal implant group were vaginal or pelvic; 7.4% (7 of 95)
      of recurrences in the pelvic radiation therapy (RT) group were vaginal and 16.8%
      were pelvic; 18.2% (8 of 44) of recurrences in the no adjuvant radiation group
      were vaginal and 31.8% pelvic. Because of the high degree of selection bias no
      valid comparisons can be made of recurrence-free interval in these groups. The 5
      year recurrence-free interval for patients with negative surgical-pathological
      risk factors (other than grade and myoinvasion) was 92.7%; involvement of the
      isthmus/cervix 69.8%; positive pelvic cytology 56.0%; vascular space invasion
      55.0%; pelvic node or adnexal metastases 57.8%; and aortic node metastases or
      gross laparotomy findings 41.2%. It is not clear that cervix invasion per se
      diminishes survival, because it is more often associated with poor tumor
      differentiation (34.7% versus 24.0%, grade 3) and deep myoinvasion (47.0 vs
      18.6%) than cases without cervix invasion. The relapse rate among cervix-positive
      and -negative cases with grade 3 lesions and deep myoinvasion is not dramatically
      different (48.8% vs 39.8%). The proportion of failures which were vaginal/pelvic
      (34.6% for the surgery only group compared to 12.5% of the RT group) appears to
      favor the use of adjuvant radiation for patients with more than one-third
      myoinvasion and grade 2 or 3 tumor. There were 97 patients in the study group
      with malignant cytology of which 29.1% had regional/distant failure, which
      compares to 10.5% of the cytology-negative patients.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 1989917
TI  - Does intraperitoneal CA-125 reflect disease status?
AB  - The relationship of serum CA-125 to intraperitoneal (IP) CA-125 was studied in 45
      patients with a variety of gynecologic diseases including ovarian carcinoma. In
      43 of 45 patients the IP level exceeded the serum level of CA-125. Paracentesis
      may dramatically alter both levels, thus mimicking surgical debulking. All IP
      levels of CA-125 measured at second-look coeliotomy for the ovarian cancer
      patients were within the normal range of IP CA-125 measured at surgery for benign
      disease. Therefore, intraperitoneal CA-125 is less sensitive than serum CA-125 in
      predicting intraperitoneal disease status. Likewise it cannot be used to predict
      the subgroup of ovarian cancer patients with negative second-look coeliotomy who
      are destined to develop a recurrence of disease.

PMID- 1989918
TI  - Fine-needle aspiration cytology accuracy with palpable gynecologic neoplasms.
AB  - From 1984 to 1988, 62 fine-needle aspirations (FNA) were performed on palpable
      lesions in 59 gynecologic oncology patients at the UCLA Medical Center. Sites of
      aspiration included abdomen, cervix, vagina, superficial lymph nodes, and pelvic
      masses. Confirmatory open biopsy (41) or adequate clinical follow-up (17) was
      obtained in 55 patients (58 aspirates). FNA correctly established the diagnosis
      of malignancy in 19 of 26 (73%) biopsied patients. The predictive value for a
      positive test was 100%, and the predictive value for a negative test was 82%.
      Initial surgical biopsy had been incorrectly benign in 4 of these patients who
      were shown subsequently to have malignant tumors by FNA and clinical findings. In
      7 patients, FNA failed to diagnose the malignancy found by open biopsy. Two of
      the false-negative FNAs were insufficient and five were in masses where palpation
      was inadequate. In 17 patients who were followed clinically without open biopsy,
      FNA correctly predicted the subsequent clinical course in 15 (88%). There were no
      false-positive FNA diagnoses obtained when cytologic results were correlated with
      both clinical outcome and surgical biopsy. Aspiration cytology has a specificity
      of 100% and a sensitivity of 65%. A negative FNA obtained from a clinically
      suspicious lesion should be followed by a repeat aspiration or surgical biopsy.

PMID- 1989919
TI  - Use of vaginal hysterectomy for the management of stage I endometrial cancer in
      the medically compromised patient.
AB  - Vaginal hysterectomy was performed on 31 patients with stage I endometrial cancer
      because of medical problems which placed them at high risk for morbidity and
      mortality from abdominal surgery. These risk factors included morbid obesity
      (87%), hypertension (58%), diabetes mellitus (35%), and cardiovascular diseases
      (26%). The perioperative morbidity was minimal, with only four patients (13%)
      experiencing complications requiring extended hospital stays and no deaths.
      Adjuvant radiotherapy was administered in 35% of patients with either deep
      myometrial invasion or unfavorable histology. The 3- and 5-year disease-free
      survival rates were 100 and 93%, respectively. The only cancer-related death
      occurred 4.5 years following surgery. Although the authors are not advocating
      vaginal hysterectomy as standard treatment of endometrial cancer, this approach
      provides an acceptable alternative to abdominal surgery in the medically
      compromised patient.

PMID- 1989920
TI  - Pseudomyxoma peritonei et ovarii associated with sequential ovarian and
      appendicular tumors and acromegaly.
AB  - Pseudomyxoma peritonei associated with highly differentiated mucinous, intestinal
      type ovarian tumor is reported in a 46-year-old acromegalic patient. Five years
      after its discovery a second operation revealed a mucinous cystadenoma of the
      appendix. The coexistence of pseudomyxoma peritonei with ovarian and appendicular
      tumors is rare, raising questions about the primary was origin of the peritoneal
      tumor. In this case the primary was ovarian while the appendicular tumor occurred
      later. Since acromegaly is associated with a high risk for the development of
      colorectal tumors, it could also have elicited a similar response in the
      intestinal-type ovarian tumor and the appendicular neoplasm found in this
      patient. The role of appendectomy in the surgical treatment and staging of
      ovarian tumors is stressed.

PMID- 1989921
TI  - A potential hazard of the use of the surgical ultrasonic aspirator in tumor
      reductive surgery.
AB  - The surgical ultrasonic aspirator (USA) is a recently developed surgical
      instrument being used for an increasingly wide range of surgical procedures
      including tumor reductive surgery in patients with advanced ovarian carcinoma.
      This paper introduces a potential hazard of the use of this instrument. It was
      determined that the mist produced by the ultrasonic aspirator during tumor
      reductive surgery contains intact and possibly viable cancer cells.

PMID- 1989922
TI  - Juvenile granulosa cell tumor in association with a high serum inhibin level.
AB  - Inhibin is a glycoprotein hormone produced mainly by ovarian granulosa cells.
      Recently measurement of serum inhibin levels was made possible by
      radioimmunoassay. We describe a patient with a juvenile granulosa cell tumor, a
      distinctive and rare form of granulosa cell tumor. This patient's serum inhibin
      level was extremely high preoperatively and returned to normal after the tumor
      was resected. This case suggests that serum inhibin level may be a useful marker
      of granulosa cell tumors.

PMID- 1989923
TI  - Paraneoplastic hypercalcemia associated with adenosquamous carcinoma of the
      endometrium.
AB  - Paraneoplastic hypercalcemia associated with adenosquamous carcinoma of the
      endometrium is described. This is the first reported case of a gynecologic cancer
      in which the paraneoplastic syndrome has been conclusively shown by
      immunohistochemical analysis to be due to ectopic parathormone.

PMID- 1989924
TI  - Rehabilitation of head and neck cancer patients: Consensus on recommendations
      from the international conference on rehabilitation of the head and cancer
      patient.

PMID- 1989925
TI  - Preliminary trial of nonrecombinant interferon alpha in recurrent squamous cell
      carcinoma of the head and neck.
AB  - Fourteen patients with recurrent squamous cell carcinoma of the head and neck
      (SCCHN) were treated with 10 x 10(6) U of nonrecombinant interferon alpha (IFN)
      intramuscularly (IM) daily for 3 days every 28 days. There were 11 men and 3
      women, with ages ranging from 48 to 74 years. Patients had previously been
      treated with surgery (9 patients), radiotherapy (13 patients), or chemotherapy (8
      patients). All patients had measurable disease by physical exam and radiologic
      evaluation and a performance status of less than or equal to 2 (ECOG). Patients
      were treated for a minimum of 3 months and continued on therapy until disease
      progression. The dose and treatment schedule of IFN was well-tolerated.
      Toxicities included low-grade fever, mild anorexia, and malaise. Treatment was
      stopped in 1 patient due to the development of atrial fibrillation. One death
      occurred as a complication of aspiration pneumonia 2 weeks following the onset of
      therapy and was not felt to be related to IFN therapy. Of the 14 patients
      treated, there was 1 complete response (30+ months) of a base of tongue primary.
      Two patients had stabilization of disease (SD, 8 and 12 months). One patient had
      a mixed response with resolution of subcutaneous nodules. The remaining 10
      patients died of progressive disease. Immunological assessment was performed on 8
      patients. The 1 patient who had a complete response was noted to have markedly
      low pretreatment natural killer (NK) cell activity and a subsequent sharp rise in
      activity after initial treatment. We conclude that low-dose cyclic IFN is well
      tolerated in patients with recurrent SCCHN and has potential antitumor activity.

PMID- 1989926
TI  - Mucosal melanoma of the head and neck.
AB  - Forty-two patients with mucosal melanoma of the head and neck were treated at the
      M. D. Anderson Cancer Center from 1944-1989. Their records were evaluated
      regarding: location of the primary, stage of the disease at presentation, type of
      treatment, location of recurrences, and overall survival. These patients received
      the majority of their therapy at M. D. Anderson Cancer Center. The treatment
      consisted of surgery, radiotherapy, chemotherapy, immunotherapy, or a combination
      of these. The 5-year survival rate was 40%. Twenty-four of 27 patients who died
      with metastatic melanoma had local or regional disease concomitantly. Forty
      percent of patients were free of disease at 5 years; however, only 26% had long
      term survival. Although the majority of patients eventually succumbed to their
      disease, local and regional control was obtained initially in 92% of the group.
      These data indicate that prolonged survival is possible with mucosal melanoma of
      the head and neck; however, recurrence or metastasis remain possible many years
      after the initial diagnosis.

PMID- 1989927
TI  - Development of surgical quality-control mechanisms in large-scale prospective
      trials: head and neck intergroup report.
AB  - One of the current national prospective clinical trials of the Head and Neck
      Intergroup explores the usage of chemotherapy in advanced operable head and neck
      cancer patients. The experimental arm consists of the addition of 3 courses of
      cisplatin-containing chemotherapy to standard treatment defined as surgery
      followed by postoperative radiotherapy. In the design of the study it is
      necessary to define not only the extent of the surgery performed for each
      eligible lesion, but also to insure uniformity of surgery performed between
      surgeons and institutions. This will hopefully insure that any variation between
      the 2 arms of the study represent the effect of the chemotherapy. The procedure
      to obtain and confirm uniformity of surgery is multifaceted. It is, however,
      fundamentally based upon the current TNM staging system and therefore has
      intrinsic limitations.

PMID- 1989929
TI  - Mandibular involvement by squamous cell carcinoma of the lower alveolus: analysis
      and comparative study of histologic and radiologic features.
AB  - Histologic analysis of squamous cell carcinoma of the lower alveolus shows 2
      basic patterns of tumor spread in relation to the mandible: an infiltrative one
      and an expansive one. While the tumor invades the mandible by destroying the bone
      or through cortical defects of some spaces in the infiltrative form, the tumor
      does this only by eroding the bone in the expansive form, in which the degree of
      bone resorption seems to be proportional to tumor advancement. A comparison
      between radiologic and histologic features discloses that the radiologically
      detected bone defects are not necessarily correlated with the patterns of bone
      involvement. However, most lesions with erosive bone defects show the expansive
      pattern histologically, and the extent of the radiologically detected bone defect
      is roughly in accordance with the histologic extent of bone involvement. These
      results lead us to believe that some squamous carcinoma of the lower alveolus
      could be treated successfully without sacrificing the continuity of the mandible.

PMID- 1989930
TI  - Analysis of the morbidity associated with immediate microvascular reconstruction
      in head and neck cancer patients.
AB  - Free tissue transfer has become an important adjunct in the reconstruction of
      head and neck cancer patients. Despite the success, the added time required to
      perform free flap reconstructions continues to be a concern for some head and
      neck surgeons. In order to investigate whether this added time increases the risk
      of medical complications to the patient, 20 consecutive free flap patients were
      compared to 20 age-, site-, and histology-matched controls. These patients were
      analyzed for demographic data, American Society of Anesthetic risk scores, stage,
      tumor site, and pre- and postoperative medical problems. The mean occurrence of
      medical problems preoperatively was 1.1 occurrences per patient for the flap
      group and 1.5 occurrences per patient for the control group. Postoperatively,
      there were 0.75 occurrences per flap group and 0.9 occurrences for the control
      group. Neither of these was statistically significant. The length of
      hospitalization was 13.5 days for the control group and 15.9 days for the flap
      group. Again, this was not statistically significant. The only significant
      statistic difference was the length of the procedure: 6.95 hours for the control
      group and 11.0 hours for the flap group, which had a p value of less than 0.001.
      In conclusion, this study indicates that length of procedure alone should not be
      a determining factor in deciding whether or not to use immediate microvascular
      reconstruction in head and neck cancer patients.

PMID- 1989928
TI  - Objective assessment of swallowing function in head and neck cancer patients.
AB  - Swallowing function was evaluated with scintigraphy in 37 patients with head and
      neck cancer. The patients were examined before and during the course of either
      surgery, chemotherapy, and/or radiotherapy. A total of 118 scintigraphic studies
      were performed. Scintigraphic results of bolus flow and aspiration were
      correlated with clinical findings. Both scintigraphic and clinical studies
      indicated a worsened swallowing function in 12 patients. These same studies
      indicated improvement of swallowing in another 13 patients. In 11 patients, both
      studies revealed either no apparent change or mixed changes in swallowing
      function after the course of therapy. In only 1 patient was there disagreement
      between the scintigraphic and clinical assessment of swallowing function. It is
      our opinion that scintigraphy is a useful method for objective assessment of
      swallowing function during and after the course of treatment of head and neck
      cancer patients.

PMID- 1989931
TI  - Neurofibroma of the vagus nerve in the head and neck: a case report.
AB  - A case of a tumor of the vagus nerve, showing typical features of a neurofibroma,
      is presented. The natural history is reviewed, and several technical
      investigations, with particular reference to the contributions of magnetic
      resonance imaging and immunohistochemical techniques in the differential
      diagnosis, are discussed.

PMID- 1989932
TI  - Congenital middle ear encephalocele initially seen with facial paresis.
AB  - Congenital middle ear encephalocele (CMEE) is a rare entity, previously reported
      in only 29 patients. It might originate from dehiscence of the tegmen tympani or
      antri or the bony plate of the posterior fossa. The common presenting symptoms
      are spontaneous cerebrospinal fluid (CSF) otorrhea and/or rhinorrhea, persistent
      "serious otitis media," conductive hearing loss, and, occasionally, recurrent
      meningitis. We report a case of CMEE initially seen with progressive facial
      paresis, review the previously reported cases of CMEE, and discuss the
      pathogenesis and surgical management.

PMID- 1989933
TI  - Merkel cell carcinoma of the ear.
AB  - All the consultants agree that, given this patient's history, a common skin tumor
      like squamous cell or basal cell carcinoma is unlikely. Melanoma or Merkel cell
      carcinoma belong in the differential. Interestingly, the consultants all suggest
      a biopsy of the lesion prior to other testing, and because this tumor is so
      accessible, a biopsy should not interfere with further testing or treatment. Drs.
      Weymuller and Marks would then proceed with a CT scan; Dr. Ridge favors an MRI
      scan. While a chest-ray is in order to rule out metastases, Dr. Weymuller also
      suggests immunocytochemistry. All the experts agree that the primary tumor should
      be excised. Dr. Weymuller would perform a total parotidectomy with facial nerve
      preservation, while Drs. Marks and Ridge suggest a superficial parotidectomy with
      facial nerve preservation. Drs. Weymuller and Ridge would also perform a modified
      radical neck dissection. In the absence of cervical disease, Dr. Marks would
      treat the neck primarily with radiotherapy. Only Dr. Weymuller favors immediate
      reconstruction and would use a lower trapezius island flap or a large rotational
      flap. Drs. Marks and Ridge prefer primary closure or skin graft. Drs. Weymuller
      and Ridge would treat this patient with combined therapy, giving radiotherapy to
      the primary area and the neck postoperatively at a dose of 55-60 Gy. However, Dr.
      Marks would treat the primary site postoperatively and the neck primarily with
      radiotherapy. He would treat the primary site with 59.40 Gy and the neck with
      50.40 Gy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1989934
TI  - Unexpected lymph node pathology in neck dissection.

PMID- 1989935
TI  - Computed tomography of the clinically negative neck.

PMID- 1989936
TI  - Historical profile. Professor Roentgen's discovery of x-rays.

PMID- 1989937
TI  - Suggested reference values for regional blood volumes in humans.
AB  - Estimates of regional blood volumes (BVs) in man are needed for the dosimetry of
      radionuclides that decay in the circulation to a significant extent. The
      tabulation of regional BVs in Publication No. 23 of the International Commission
      on Radiological Protection (ICRP Reference Man document) may be the best
      available for dosimetric applications but is not consistent with current
      information for some organs and does not address some important blood pools. The
      purpose of this paper is to suggest an improved set of reference values for
      regional BVs in adult humans. The total blood volume (TBV) is viewed as
      comprising 22 separate pools, including several pools not addressed in the ICRP
      Reference Man document. Values suggested here for brain, liver, skin, active
      marrow, inactive marrow, and bone differ by at least a factor of two from those
      given for ICRP Reference Man.

PMID- 1989938
TI  - Radium-226 whole-body gamma counting and 222Rn breath analysis: report on a
      subject exposed to uranium mill tailings.
AB  - One of two boys born in September 1949 who played on U mill tailings between age
      8 and 12 was diagnosed as having leukemia at age 15.5. The exposed and control
      subjects were well matched; they were approximately the same age and both were
      1.85 m (6' 1") in height and weighed 75.2 kg (165 pounds). The result obtained by
      gamma spectrometric method for the exposed subject was 0 +/- 17 Bq (0 +/- 470
      pCi), while that for the control subject was 4 +/- 15 Bq (100 +/- 400 pCi). The
      result obtained by the Rn breath method for the exposed subject was 4.4 +/- 0.7
      Bq (120 +/- 20 pCi), while that for the control was 5.4 +/- 1.4 Bq (150 +/- 38
      pCi). These results suggest that the 226Ra body burden of the exposed subject is
      within the range of those observed in subjects exposed only through normal food
      sources, which have a mean 226Ra content of 1.5 Bq (range: 0.4-4.4 Bq) so that no
      significant mill-tailing intake is indicated. The best estimate of alpha particle
      dose to the red marrow from 226Ra and its decay products was 0.05 mGy at age 14
      and 0.10 mGy at age 38. This dose, when compared to that observed in the dial
      painters, suggests that the leukemia was not caused by uptake of Ra from the mill
      tailings.

PMID- 1989939
TI  - An improved 222Rn canister using a two-stage charcoal system.
AB  - A prototype for an improved passive 222Rn canister (R-Canister) was designed and
      compared to conventional charcoal canisters for its adsorptive and desorptive
      characteristics following exposures to 222Rn at 23 degrees C in the presence of
      water vapor. The R-Canister, containing a two-stage charcoal system, minimizes
      the adverse effects of water vapor by maintaining the amount of adsorbed water
      vapor in the primary Rn adsorbent below the "break-point" of the charcoal. This
      is achieved by the placement of a desiccant charcoal cartridge 6 cm above the
      primary Rn adsorbent. The optimal bed depth of the primary adsorbent, determined
      from a diffusion study, was found to be 2.3 cm. The measured value for the
      effective diffusion coefficient of RN in a peat-based charcoal at 15% humidity
      and 25 degrees C is 7.97 x 10(-10) m2 s-1. Exposures to 70% humidity for 7 d
      increased the buildup time-constant of Rn in the R-Canisters by 33% as compared
      to R-Canisters exposed to 15% humidity. At relative humidities ranging from 15
      70%, the 222Rn buildup time-constant of the R-Canister ranged from 43-94 h,
      whereas the desorption time-constant ranged from 46-64 h. Typical buildup time
      constants and desorption time-constants for conventional fully-opened charcoal
      canisters currently in field use ranged from 30-43 h and 17-29 h, respectively,
      over the same range of humidities.

PMID- 1989941
TI  - Assessment of radiocesium incorporation in Austrians after the Chernobyl
      accident.
AB  - Residents of Vienna, Austria were whole-body counted for radiocesium content due
      to fallout deposited after the Chernobyl accident. Data for a 2-y period were
      compared with prior estimates of radiocesium body burden based on food
      consumption. Our results suggest that the prior estimates be revised and the
      rejection limit be increased by a factor of 2 for contaminated food.

PMID- 1989940
TI  - Summertime elevation of 222Rn levels in Huntsville, Alabama.
AB  - Indoor Rn concentrations and Rn in adjacent karst terrains were studied at four
      houses with crawlspaces in Huntsville, AL. In warm summertime weather, Rn-rich
      air may vent through limestone solution cavities exposed as holes at the surface
      of the properties. A probable interrelated-finding is that the indoor levels of
      222Rn are distinctly higher in the summer than winter. The karst underlying the
      homes is structurally faulted and, in all probability, facilitates Rn transport
      from the solution cavities to the crawlspaces. Abrupt day-to-day changes in
      indoor Rn concentrations were recorded in addition to large seasonal changes. If
      the owners or residents of these particular homes had attempted to make, and
      interpret, short-term screening measurements for Rn during the fall season,
      problems, including false negatives, could have arisen because of order-of
      magnitude changes in Rn concentration occurring over a few days. The best time of
      year to make screening measurements would be during the summer when indoor Rn
      concentrations are more likely to reach their maximum values.

PMID- 1989942
TI  - Human postmortem thyroid 131I content and risk estimates in Bratislava,
      Czechoslovakia following the Chernobyl accident.
AB  - From 3 May to 4 August 1986, thyroids of 416 postmortem subjects in Bratislava
      (population: approximately 400,000) were measured for 131I. Subsequently, dose
      rates in this organ for the day of exitus were calculated. Mean dose commitments
      were estimated by integrating linear or quadratic-periodic regression lines drawn
      through scatterplots of logarithmically transformed daily dose rates. The mean
      dose-commitment estimates in thyroids of adults were 0.74 and 0.58 mGy for linear
      and quadratic-periodic regression, respectively. The same for thyroids obtained
      from donors of fetal to 18 y of age were 1.67 and 1.77 mGy for liner and
      quadratic-periodic regression, respectively. A comparison of the actual thyroid
      radiation burden with its theoretical values calculated in the first days of
      contamination of the environment showed that the models used were safe enough to
      protect the population. Estimates of absolute risk for thyroid cancer showed that
      excess incidence that could be expected as a result of the Chernobyl accident
      shall remain obscured by the "spontaneous" incidence of this disease at
      geographic localization.

PMID- 1989943
TI  - Thermalization of accelerator-produced neutrons in a concrete room.
AB  - We investigated a thermalization of neutrons, which were produced by an
      accelerator in a concrete room, by experiments and calculations. It was clarified
      that the widely used simple empirical formula phi th = c x Q/S, where Q is the
      neutron source intensity and S is the total surface area of a room, gives about
      one-third the underestimated value to our experimental and calculated results and
      the coefficient, c, is not a constant, but dependent on the source neutron
      energy.

PMID- 1989944
TI  - Radon concentrations in ground water of the Georgia Piedmont.

PMID- 1989945
TI  - Survey of indoor 222Rn concentrations in Hong Kong.

PMID- 1989946
TI  - Radon levels in United States homes by states and counties.
AB  - Results of 175,000 purchased Rn levels are presented by county and by state. Bias
      elimination techniques are described, and correlations with random selection-no
      charge studies are presented.

PMID- 1989947
TI  - Influence of Prussian blue in reducing transfer of radiocesium into ovine milk.

PMID- 1989948
TI  - Hand dose measurements in interventional radiology.
AB  - Measurements of radiation dose to the hand were conducted using TLD ring badges
      for individual interventional radiology cases. Results from over 30 examinations
      (including transhepatic cholangiograms and biliary and nephrostomy procedures)
      conducted by four radiologists using identical equipment show an average hand
      dose of 1.5 mGy (150 mrad) per procedure. Hand dose varied inversely with
      distance from the patient. Due to variable hand positions during clinical
      examinations, fluoroscopic time was not found to be a good indicator of hand
      dose.

PMID- 1989949
TI  - Performance characteristics of a commercial dedicated contamination counter.
AB  - The dedicated wipe test counter (DWTC) is a commercial geiger-counter type
      instrument especially designed for wipe test counting. All samples are counted
      under the same physical conditions within 0.3 cm from a 2-mg cm-2 mica end-window
      geiger tube of 1.27 cm in diameter. The counting capabilities of the DWTC were
      tested for different radioisotopes in common use in the nuclear medicine
      laboratory. Since most of the imaging agents are 99mTc-based
      radiopharmaceuticals, an experimental efficiency factor, J = 3 cpm kdpm-1, was
      determined for this radioisotope by the manufacturer and stored in the counting
      system for default use. In addition, the formulation for the counting time needed
      to achieve a measurement with adequate level of significance (two standard
      deviations) and a background measurement time of 20 min was programmed in the
      firmware of the DWTC. With these parameters, the counting time for a 99mTc wipe
      (threshold of 2000 dpm) becomes 1.88 min for a background level of 10 cpm. The
      counting time increases to 3.25 and 4.80 min for the respective background levels
      of 20 and 30 cpm while the threshold is kept the same. In practice, we were able
      to measure activities as low as 0.7 kdpm for 99mTc and 0.09 kdpm for 131I.
      Linearity was maintained for a wide range of activities for all tested
      radioisotopes. The DWTC was found to be simple to operate and satisfies all
      requirements for performing wipe tests in the nuclear medicine laboratory.

PMID- 1989950
TI  - Radon calibration factor for charcoal canisters.

PMID- 1989951
TI  - Response to 'Supra-linear dose-response in the A-bomb study'.

PMID- 1989952
TI  - Cancer dose-response in A-bomb survivors: erroneous basis of Izatt's 'fairly
      conclusive evidence' for hormesis.

PMID- 1989953
TI  - Women at midlife and beyond.

PMID- 1989954
TI  - Change-of-life anticipations, attitudes, and experiences among middle-aged Danish
      women.
AB  - The meaning of the lay concept "the change of life" and the possible impact of
      the change of life on women's perceptions of health, aging, and sexuality in
      relation to this event was studied in a Danish general population. Longitudinal
      analyses were based on data from three cross-sectional studies carried out in
      1976, 1981, and 1987 on a cohort of Danish women born in 1936. Of the original
      population of 621 women, 474 (76%) participated in all three studies. In a
      subsample (n = 336) consisting of women who assessed themselves as having
      experienced the change of life, the majority did not report loss of health,
      youth, or sexuality in relation to the climacterium. Social, cultural, and
      psychological factors unrelated to hormonal changes were of significant
      importance for the quality of health and sexuality during this period.

PMID- 1989955
TI  - Burden of care: an important concept for nurses.
AB  - Research on family caregiving demonstrates clearly the predominance of women,
      particularly wives and adult daughters, among the care providers to elderly
      persons who are frail and chronically ill. It seems that women go to great
      lengths to care for impaired and elderly relatives, making personal sacrifices,
      often at great cost to their own health and well-being. Burden of care is a
      concept emerging in the literature that describes the physical, emotional,
      social, and financial problems that can be experienced by family caregivers. This
      concept may be useful to heighten understanding of the family caregiving
      experience and as such may provide a framework for nursing practice and research.
      We seek to increase nurses' awareness, through an examination of the burden-of
      care literature, of the caregiving experience of women who minister to elderly
      parents and husbands. We also make a plea for the involvement of nurses with both
      givers and receivers of care and offer an approach to assessment that
      incorporates both the meaning and the process of caregiving.

PMID- 1989956
TI  - Spousal caregiving in later life: an objective and subjective career.
AB  - During later life, as a consequence of the deteriorating health of husbands,
      numerous women experience a period of spousal caregiving that can be considered a
      new phase in their caregiving career. This phase, which often precedes widowhood,
      is one that has been relatively neglected by researchers. In this article, the
      concepts of objective and subjective career (Hughes, 1971) are used as orienting
      concepts to examine the phenomenon of spousal caregiving in later life.
      Objectively, the caregiving career is seen as an age-related, gender-specific,
      and role-contingent phenomenon. The subjective career is seen as the meaning and
      purposes attributed to complex and extensive responsibilities and activities of
      caregiving and their potentially serious consequences for health and well-being.

PMID- 1989957
TI  - Emily: a study of grief and bereavement.
AB  - The author's purpose in presenting this article is to describe and interpret the
      phenomena that contributed to a state of extended bereavement in an 83-year-old
      window. The problem concerned a newly admitted nursing home resident who appeared
      to be experiencing profound grief at the loss of a husband who had died 12 years
      earlier. The method was qualitative, specifically, ethnographic. This case study
      focuses on the life history of one individual as she perceived it. The question
      posed for the study was what are the factors contributing to a grief reaction in
      an elderly widow 12 years after her husband's death? To answer this question a
      series of interviews were conducted with the informant. The data were then
      analyzed for meaning in light of current theory in grief and bereavement. The
      findings, presented in the informant's words, highlight the importance of
      suddenness, multiplicity of losses, relationship with the deceased spouse, and
      personal characteristics of the bereaved.

PMID- 1989958
TI  - Self-care and menopause: critical review of research.
AB  - Existing literature on self-care as it relates to menopause is examined to
      determine whether the knowledge base in this area reflects important tenets in
      women's health. One such tenet is that understanding the lived experience of
      women is critical in developing effective health care interventions. Few
      investigators acknowledge the lived experience of women in their studies of self
      care and menopause.

PMID- 1989959
TI  - The meanings of menopause.
AB  - Multiple meanings have been assigned to menopause and to women experiencing
      menopause. Meanings are not inherent in reality but are assigned by humans in
      response to interaction. Once meanings are assigned to entities, they become
      coercive and influence interactions. Freidson's (1988) theoretical framework
      includes the imputation of responsibility, legitimacy, and seriousness to a
      deviance or illness and provides the basis for an analysis of the various
      meanings of menopause that are found in the literature. This analysis is
      concerned with the social, political, economic, and health care consequences of
      the assigned meanings of menopause for women.

PMID- 1989960
TI  - The meaning of time: Mohawk women at midlife.
AB  - Midlife has emerged as an important developmental transitional point for both men
      and women. For women, menopause is synonymous with midlife, and consequently
      women and health professionals have focused on the losses and problems of this
      biological event. Few studies to date have placed menopause within the context of
      other life experiences occurring at this time and in varied cultural groups.
      Eight Mohawk women, aged 45 to 54 years, were visited in their homes on a weekly
      or bimonthly basis spanning a 6- to 8-week period. Using a grounded theory
      approach, the women were encouraged to describe their experiences at this time.
      The four major issues experienced at midlife related to the concept of time: it
      is time for me, being where I should be, time for myself, and my time is spent
      meaningfully. Women fell into two groups. Those "in synchrony" viewed their lives
      as following expected time pathways. Those "out of synchrony" identified aspects
      of their lives as problematic. Of the four women who were out of synchrony, three
      were "action oriented" and the fourth was "stuck."

PMID- 1989961
TI  - The theory of reasoned action in prediction of breast self-examination: a
      comparison of two studies.
AB  - The purpose of this article is to report the application of the theory of
      reasoned action (TRA) to predict breast self-examination (BSE) intention and
      frequency in two studies with middle-aged and older women. The sample in Study 1
      consisted of 93 volunteers from church groups; the second sample consisted of 175
      randomly selected subscribers to a large health maintenance organization.
      Questionnaires to measure attitudinal and subjective normative influences
      relevant to BSE were developed using guidelines specified by Ajzen and Fishbein
      (1980). The attitudinal components predicted BSE intention in both studies and
      BSE frequency in Study 1. In contrast, the subjective norm contributed
      significantly only to the prediction of frequency in Study 1. Findings
      demonstrate varying degrees of success for the TRA in predicting BSE intention
      and behavior. Explanations for the inconsistency in the predictive ability of the
      TRA can be related to differences between the two studies regarding sample and
      design characteristics.

PMID- 1989962
TI  - Comparing methods of reporting breast self-examination compliance.
AB  - Women volunteers (N = 32) learning breast self-examination (BSE) in one of
      several small group workshops were asked to practice BSE on a monthly basis and
      reported BSE practice for the following 6 months. Each workshop was randomly
      assigned to one of three methods of reporting subsequent instances of BSE: (a)
      retrospective reporting in which they were called by the experimenter and asked
      how many times they performed BSE; (b) monthly written reports, in which they
      mailed in a card after each month's practice of BSE; and (c) an oil-and-tissue
      method in which, in addition to the card, they mailed in a tissue that they had
      used to blot oil used as a lubricant in BSE. Rates of self-reported BSE for the
      three methods were compared, showing no differences between the oil-and-tissue
      method and the monthly written report method, with rates for both methods
      significantly lower than for the retrospective report method. It was concluded
      that the monthly report method provides the same information as the oil-and
      tissue method, without its awkwardness and expense, and thus seems the preferred
      method of self-report in BSE studies.

PMID- 1989963
TI  - Identifying women's descriptions of breast tissue for the promotion of breast
      self-examination.
AB  - The purpose of this study was to identify women's descriptions of their breast
      tissue. Concrete objective descriptions of the breast, in women's own words, are
      important to formulate an intervention, based on a self-regulation framework,
      designed to promote breast self-examination. Descriptions were initially
      generated from open-ended interviews with 27 women scheduled for mammography. The
      initial descriptions were validated by an additional 25 women scheduled for
      mammography. The descriptions of the breast that are relevant to women are
      presented, conclusions for a subsequent intervention study drawn, and
      implications for practice addressed.

PMID- 1989964
TI  - Stress, emotions, and coping: a study of elderly women with osteoarthritis.
AB  - My purpose in conducting this study was to identify and describe the illness
      related stressors and emotions experienced by elderly women with osteoarthritis
      and the coping strategies they used to manage these situations. The theoretical
      framework for the investigation was based on a process theory of stress and
      coping developed by Lazarus and Folkman (1984). In a home interview, 90 women
      completed a demographic profile and identified concerns, feelings, and coping
      strategies used to manage problems associated with osteoarthritis. Descriptive
      statistics and content analysis of data indicated that the stress of
      osteoarthritis involved physical, social, and psychological aspects of life and
      evoked both positive and negative feelings. The women used a broad repertoire of
      coping behaviors, including problem- and emotion-focused strategies to manage the
      problems associated with osteoarthritis in their day-to-day life. This
      information has implications in both treatment and prevention areas for health
      professionals who provide services for this group of people.

PMID- 1989965
TI  - Life satisfaction in women with postmenopausal osteoporosis of the spine.
AB  - This exploratory-descriptive study was undertaken to determine what combination
      of variables was the best predictor of life satisfaction in women with
      postmenopausal osteoporosis of the spine and vertebral fractures. A sample of 93
      women, drawn from private osteoporosis clinics, completed the four research
      questionnaires. Data were analyzed using means, standard deviations, product
      moment correlations, and stepwise multiple regression analysis. Analysis of the
      data revealed that there were significant predictors of life satisfaction in this
      group. Life satisfaction was best predicted by the following combination of
      variables: income level, frequency of back pain, perceived internal control over
      health, and perceived social support.

PMID- 1989966
TI  - Metal-catalyzed oxidation of proteins. Physiological consequences.

PMID- 1989967
TI  - Sphingosine inhibits phosphatidate phosphohydrolase in human neutrophils by a
      protein kinase C-independent mechanism.
AB  - Human neutrophils have been labeled in 1-O-alkyl-phosphatidylcholine with 3H in
      both the alkyl chain and the choline moiety. Upon stimulation of these labeled
      cells with formyl-Met-Leu-Phe, C5a, or phorbol 12-myristate 13-acetate,
      phospholipase D is activated to produce 1-O-[3H]alkylphosphatidic acid ([3H]alkyl
      PA) and [3H]choline. The [3H]alkyl-PA is then dephosphorylated by phosphatidate
      phosphohydrolase (PPH) to produce 1-O-[3H]alkyldiglyceride ([3H]alkyl-DG).
      Sphingosine, a sphingoid base known to inhibit protein kinase C (PKC), causes a
      dose-dependent inhibition of [3H]alkyl-DG formation. This inhibition is
      accompanied by increased accumulation of [3H]alkyl-PA without alterations in
      [3H]choline formation. Studies using various other sphingoid bases demonstrate
      that a long hydrocarbon chain and an amino group are required for the inhibition
      of DG formation. These results suggest that sphingoid bases inhibit PPH activity
      without altering phospholipase D activation and that they exhibit a similar
      structure-activity relationship for both PPH and PKC. K252a, a PKC inhibitor
      which acts by competing for ATP binding sites, does not inhibit the formation of
      [3H]alkyl-DG, [3H]alkyl-PA, or [3H]choline at a concentration (3 microM) that
      completely blocks phorbol 12-myristate 13-acetate-induced protein
      phosphorylation. Moreover, in neutrophil homogenates, sphingosine but not
      octylamine, inhibits PPH activity in a dose-dependent manner. Thus sphingosine
      inhibits PPH activity by a PKC-independent mechanism, raising the possibility
      that sphingoid bases may play a role in regulating PPH-mediated lipid metabolism
      in stimulated cells.

PMID- 1989968
TI  - Molecular cloning and characterization of complementary DNA encoding for
      ferredoxin-dependent glutamate synthase in maize leaf.
AB  - The sequence of ferredoxin-dependent glutamate synthase (EC 1.4.7.1) mRNA from
      maize has been determined. Complementary DNAs were isolated from a cDNA library
      of light-induced leaf poly(A)+ RNA constructed in an expression vector. An open
      reading frame beginning at an ATG codon at nucleotide 328 of the longest cDNA
      (5617-bases long) encoded 1616 amino acid residues. The amino terminus of the
      purified mature enzyme coincided with the cysteine residue at position 98 of the
      predicted sequence. This enzyme is homologous with the large subunit of
      Escherichia coli NADPH-dependent glutamate synthase having about 42% identical
      residues between the two proteins. The enzyme also contains a short region
      similar to a potential FMN-binding region of yeast flavocytochrome b2. The cDNA
      hybridizes to an RNA band about 5.5 kilobases whose steady-state level is
      markedly increased upon illumination of etiolated maize seedlings. Analysis of
      genomic DNA indicates the presence of a single-copy gene for ferredoxin glutamate
      synthase in maize.

PMID- 1989969
TI  - A human autoantibody specific for a unique conserved region of 28 S ribosomal RNA
      inhibits the interaction of elongation factors 1 alpha and 2 with ribosomes.
AB  - An autoantibody reactive with a conserved sequence of 28 S rRNA (anti-28 S) was
      identified in serum from a patient with systemic lupus erythematosus. Anti-28 S
      protected a unique 59-nucleotide fragment synthesized in vitro against RNase T1
      digestion. RNA sequence analysis revealed that it corresponded to residues 1944
      2002 in human 28 S rRNA and 1767-1825 in mouse 28 S rRNA. These sequences are
      identical and highly conserved throughout all known eukaryotic 28 S rRNAs. In
      addition, this fragment is homologous to residues 1052-1110 of Escherichia coli
      23 S rRNA that lies within the GTP hydrolysis center of the 50 S ribosomal
      subunit. Anti-28 S and its Fab fragments strongly inhibited poly(U)-directed
      polyphenylalanine synthesis, but had no effect on ribosomal peptidyltransferase
      activity. This effect resulted from inhibition of the binding of elongation
      factors EF-1 alpha and EF-2 to ribosomes and of the associated GTP hydrolysis.
      The inhibitory effect was almost completely suppressed by preincubation of anti
      28 S with 28 S rRNA or in vitro synthesized RNA fragments containing the
      immunoreactive region. These results show that the immunoreactive conserved
      region of 28 S rRNA participates in the interaction of ribosomes with the two
      elongation factors in protein synthesis.

PMID- 1989970
TI  - The modulation of rat brain Na(+)-Ca2+ exchange by K+.
AB  - The involvement of potassium ions in the Na(+)-Ca2+ exchange process was studied
      in rat brain synaptic plasma membrane (SPM) vesicles. Addition of equimolar [K+]
      to the intravesicular and the extravesicular medium led to a stimulation of the
      Na+ gradient-dependent Ca2+ influx; this stimulation was noticeable already at
      0.5 mM and reached its maximum at 2 mM K+. The magnitude of the K+ stimulation
      was between 1.3-2.5-fold in different SPM preparations. K+ ions also stimulated
      the Na(+)-dependent Ca2+ efflux. K+ stimulation of Na(+)-Ca2+ exchange is of
      considerable specificity, since it is not mimicked by either Li+ or H+. The
      following lines of evidence suggest that K+ modulation of Na(+)-Ca2+ exchange
      involves the catalytic moiety of the transporter itself and not an unrelated K+
      channel which modulates the membrane potential. 1) K+ stimulation of the
      transport process was conserved following reconstitution of the transporter into
      phospholipid-rich liposomes, an experimental condition which presumably separates
      the native membrane proteins among different vesicular structures. 2) K+
      stimulation of Na+ gradient-dependent Ca2+ influx persists also when the build up
      of negative inside membrane potential is prevented by addition of carbonyl
      cyanide p-trifluoromethoxy phenylhydrazone which renders the membrane highly
      permeable to protons both in the native and the reconstituted preparation. 3) K+
      stimulation of Na+ gradient-dependent Ca2+ influx is obtained also when
      tetraethylammonium chloride, 2,3-diaminopyridine and Cs+ are added to the Ca2+
      uptake medium. Reconstituted SPM vesicles take up 86Rb+ in response to activation
      of Na+ gradient-dependent Ca2+ influx. The ratio of Ca2+ taken up by SPM vesicles
      in a Na+ gradient-dependent manner to the corresponding amounts of Rb+ taken up
      varies between 8-5 in different SPM preparations. If the stoichiometry of the
      process is 1 Rb+/1 Ca2+, then Rb+ cotransport is mediated by 10-20% of the
      transporters present in the preparation.

PMID- 1989971
TI  - Studies on the activity and activation of rat liver microsomal glutathione
      transferase with a series of glutathione analogues.
AB  - The substrate specificity of rat liver microsomal glutathione transferase toward
      glutathione has been examined in a systematic manner. Out of a glycyl-modified
      and eight gamma-glutamyl-modified glutathione analogues, it was found that four
      (glutaryl-L-Cys-Gly, alpha-L-Glu-L-Cys-Gly, alpha-D-Glu-L-Cys-Gly, and gamma-L
      Glu-L-Cys-beta-Ala) function as substrates. The kinetic parameters for three of
      these substrates (the alpha-D-Glu-L-Cys-Gly analogue gave very low activity) were
      compared with those of GSH with both unactivated and the N-ethylmaleimide
      activated microsomal glutathione transferase. The alpha-L-Glu-L-Cys-Gly analogue
      is similar to GSH in that it has a higher kcat (6.9 versus 0.6 s-1) value with
      the activated enzyme compared with the unactivated enzyme but displays a high Km
      (6 versus 11 mM) with both forms. Glutaryl-L-Cys-Gly, in contrast, exhibited a
      similar kcat (8.9 versus 6.7 s-1) with the N-ethylmaleimide-treated enzyme but
      retains a higher Km value (50 versus 15 mM). Thus, the alpha-amino group of the
      glutamyl residue in GSH is important for the activity of the activated microsomal
      glutathione transferase. These observations were quantitated by analyzing the
      changes in the Gibbs free energy of binding calculated from the changes in
      kcat/Km values, comparing the analogues to GSH and each other. It is estimated
      that the binding energy of the alpha-amino group of the glutamyl residue in GSH
      contributes 9.7 kJ/mol to catalysis by the activated enzyme, whereas the
      corresponding value for the unactivated enzyme is 3.2 kJ/mol. The importance of
      the acidic functions in glutathione is also evident as shown by the lack of
      activity with 4-aminobutyric acid-L-Cys-Gly and the low kcat/Km values with gamma
      L-Glu-L-Cys-beta-Ala (0.03 and 0.01 mM-1s-1 for unactivated and activated enzyme,
      respectively). Utilization of binding energy from a correctly positioned carboxyl
      group in the glycine residue (10 and 17 kJ/mol for unactivated and activated
      enzyme, respectively) therefore also appears to be required for optimal activity
      and activation. A conformational change in the microsomal glutathione transferase
      upon treatment with N-ethylmaleimide or trypsin, which allows utilization of
      binding energy from the alpha-amino group of GSH as well as the glycine carboxyl
      in catalysis, is suggested to account for at least part of the activation of the
      enzyme.

PMID- 1989973
TI  - Alloxan-induced DNA strand breaks in pancreatic islets. Evidence for H2O2 as an
      intermediate.
AB  - Alloxan exhibits the most potent diabetogenicity and has been used for induction
      of experimental diabetes mellitus. Understanding the mechanisms of action of the
      typical diabetogenic agent is important for elucidating the causes of diabetes.
      Okamoto (Okamoto, H. (1985) BioEssays 2, 15-21) proposed a model in which DNA
      fragmentation plays an important role for the development of diabetes. This DNA
      fragmentation is supposed to result from the accumulation of superoxide or
      hydroxyl radicals. However, direct evidence for this accumulation is lacking.
      Using rat pancreatic islets, we demonstrated that alloxan stimulated H2O2
      generation, which induced DNA strand breaks. These findings support Okamoto's
      proposal that alloxan induces diabetes through the following biochemical events:
      alloxan----H2O2 generation----DNA strand breaks----diabetes mellitus. Perhaps
      this report constitutes the first demonstration of alloxan-stimulated H2O2
      generation which could conceivably act as an intermediate for alloxan-induced DNA
      strand breaks.

PMID- 1989972
TI  - Nuclear Overhauser effect studies on the conformations of Mg(alpha,beta
      methylene)ATP bound to Escherichia coli methionyl-tRNA synthetase.
AB  - Internuclear distances obtained from nuclear Overhauser effects were used in
      combination with a distance geometry algorithm to determine the conformation of
      Mg(alpha,beta-methylene)ATP bound to the Escherichia coli truncated methionyl
      tRNA synthetase (delta MTS) both in the absence and presence of cognate and
      noncognate amino acids. Mg(alpha,beta-methylene)ATP, a nonhydrolyzable analog of
      ATP, was used to prevent hydrolysis of the nucleotide in the presence of either
      cognate or noncognate amino acids. Kinetic analysis showed that Mg(alpha,beta
      methylene)ATP was a linear competitive inhibitor with respect to ATP in the ATP
      pyrophosphate exchange reaction with a Ki = 1.2 mM. The pattern of internuclear
      Overhauser effects on Mg(alpha,beta-methylene)ATP bound to delta MTS was
      qualitatively consistent only with an anti glycosidic torsional angle, suggesting
      that the adenosine portion of the nucleotide is uniquely oriented in the binary
      enzyme-nucleotide complex. Nearly identical patterns of nuclear Overhauser
      effects were also observed in ternary complexes containing either cognate L
      methionine or noncognate L-homocysteine amino acids. Distance geometry
      calculations permitted the range and conformational space of the allowed adenine
      ribose glycosidic torsional angles in each of the complexes to be better defined
      and compared. Average adenine-ribose glycosidic torsional angles for enzyme-bound
      Mg(alpha,beta-methylene)ATP of -106 +/- 9 degrees, -99 +/- 11 degrees, and -97 +/
      11 degrees were determined for the delta MTS.Mg(alpha,beta-methylene)ATP, delta
      MTS.Mg(alpha,beta-methylene)ATP.L-methionine, and delta MTS.Mg(alpha,beta
      methylene)ATP.L-homocysteine complexes, respectively. Comparison of the three
      enzyme-bound conformations showed that a single nucleotide structure having an
      adenine-ribose glycosidic torsional angle of -98 degrees with a 3'-endo to O4'
      exo ribose sugar pucker was, within error, consistent with the experimental
      internuclear distances obtained in all three complexes. The nearly identical anti
      glycosidic torsional angles observed in all three complexes demonstrates that the
      conformation of the adenosine moiety of the enzyme-bound nucleotide is not
      sensitive to the presence or the nature of the amino acid bound at the
      aminoacyladenylate site. Therefore, conformational changes known to occur in the
      methionyl-tRNA synthetase upon ligand binding appear not to alter the bound
      conformation of the nucleotide. Information on the conformation and arrangement
      of substrates bound at the aminoacyladenylate site of delta MTS is necessary for
      understanding the molecular mechanisms involved in amino acid activation and
      discrimination.

PMID- 1989974
TI  - A novel trypsin inhibitor from the hemolymph of the horseshoe crab Limulus
      polyphemus.
AB  - Trypsin inhibitory activity from the hemolymph of Limulus polyphemus was found to
      co-purify with coagulogen (the clottable protein in blood coagulation) after
      acidification, ammonium sulfate precipitation, and gel filtration. Limulus
      trypsin inhibitor (LTI) was separated from coagulogen by ion-exchange
      chromatography on carboxymethyl-Sephadex. LTI is an inhibitor of trypsin (Ki =
      3.3 nM) on both high and low molecular weight substrates. It also inhibits
      chymotrypsin but has little or no effect on thrombin, thermolysin, pepsin, or
      papain, nor does LTI inhibit the proteolytic cascade produced in endotoxin
      stimulated Limulus amoebocyte lysate coagulation. Electrophoresis under
      nonreducing conditions on denaturing polyacrylamide gel yields a doublet
      migrating with an estimated Mr of 20,000. Under reducing conditions, a single
      broad band migrates with an estimated Mr of 15,000. The native structure is a
      monomer of moderate asymmetry with a molecular weight of 16,300 and a so20,w =
      1.5(5), as determined by analytical ultracentrifugation. The amino acid
      composition of LTI yields a calculated molecular weight of 15,680 and a
      calculated partial specific volume of 0.71(7) ml/g. LTI does not contain
      methionine, tryptophan, or detectable levels of reducing carbohydrate. The NH2
      terminal sequence (V-S-P-P-F-I-K-Q-T-K-F-S-T-X-F-L-G-X-S-S) consists primarily of
      hydrophobic amino acid residues. Comparison of the amino acid composition and
      amino-terminal sequence of LTI with those of other known protease inhibitors
      reveals no significant similarity to other trypsin inhibitors. The novel physical
      characteristics suggest that LTI represents a new type of protease inhibitor.

PMID- 1989975
TI  - Measurement of instant rates of protein degradation in the livers of intact mice
      by the accumulation of bestatin-induced peptides.
AB  - Bestatin induces the accumulation of di- and tripeptide intermediates in cellular
      protein breakdown. In liver, a single set of bestatin-sensitive cytosolic
      peptidases are involved in the degradation to amino acids of the major classes of
      cellular proteins. Accumulation of bestatin-induced peptides, in isolated
      hepatocytes, is proportional to the rate of protein degradation (Botbol, V., and
      Scornik, O. A. (1989) J. Biol. Chem. 264, 13504-13509). Injection of 1 mg of
      bestatin into mice results in detectable amounts of hepatic intermediates in 15
      min. We propose to use the accumulation of these peptides as a relative
      measurement of liver protein degradation. There is at present no other way to
      determine transient changes in protein breakdown in the tissues of intact
      animals. As an example of the applications of this procedure, we present the
      effects of a single meal on hepatic protein metabolism. Protein synthesis was
      estimated by the incorporation into liver protein of a massive dose of
      radioactive leucine (Scornik, O. A. (1974) J. Biol. Chem. 249, 3876-3883) and
      degradation of long-lived or short-lived proteins by the accumulation of bestatin
      induced peptides, labeled in carboxy-C of their Leu or Arg moieties, 1 day or 1 h
      beforehand. A single meal resulted in an 18% increase in liver protein in 8 h, a
      45% increase in the rate of hepatic protein synthesis, and a 3-fold decrease in
      the rate of breakdown of long-lived proteins. Short-lived proteins were not
      affected. To establish the efficiency with which bestatin-induced peptides
      accumulate in the livers of fasting mice, we compared them with the
      disappearance, in 1 day, of protein-bound 14C-guanidino-Arg residues, labeled by
      previous injection of 14C-bicarbonate (Swick, R. W., and Ip, M. M. (1974) J.
      Biol. Chem. 249, 6836-6841). From this comparison, we estimated that bestatin
      induced Leu-labeled intermediates, accumulating in 15 min, represented 39% of the
      hepatic proteins degraded in that interval. For Arg-labeled intermediates the
      value was 55%. Correcting for these efficiencies, we estimate that in 4 h a meal
      decreased the rate of degradation of long-lived Arg-labeled proteins from 2.02 to
      0.73%/h. For Leu-labeled proteins the estimated rates were 1.76 and 0.66%/h,
      respectively. Although a transient slowdown of liver protein degradation after a
      single meal had been suggested before, this is the first time that acute changes
      such as this can be determined directly in intact animals.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 1989976
TI  - Phospholipid-independent and -dependent interactions required for tissue factor
      receptor and cofactor function.
AB  - Membrane anchoring of tissue factor (TF), the cell receptor for coagulation
      factor VIIa (VIIa), exemplifies an effective mechanism to localize proteolysis at
      the cell surface. A recombinant TF mutant (TF1-219), deleted of membrane spanning
      and intracellular domains, was used to evaluate the role of phospholipid
      interactions for assembly of substrate with the catalytic TF.VIIa complex. TF1
      219 was secreted by cells rather than expressed as a cell membrane protein.
      Unlike free VIIa, TF1-219 as well as the TF1-219.VIIa complex demonstrated no
      stable association with phospholipid. In the absence of lipid, kinetic evaluation
      of substrate factor X cleavage by free VIIa, TF.VIIa, and TF1-219.VIIa suggests
      that the catalytic function of VIIa rather than substrate recognition is enhanced
      by complex formation. Furthermore, compared with free factor X, factor X on
      phospholipid was preferentially cleaved as a substrate by TF1-219.VIIa. TF
      dependent initiation of the coagulation protease cascades thus involves an
      enhancement of the activation of factor X on the cell surface by a crucial role
      of the TF transmembrane domain to membrane anchor the reaction, by the TF
      extracellular domain to provide protein-protein interactions with VIIa to enhance
      the activity of the catalytic domain of VIIa, and the preferential presentation
      of factor X as a substrate when associated with phospholipid surfaces.

PMID- 1989977
TI  - Definition of a C-reactive protein binding determinant on histones.
AB  - C-reactive protein (CRP) is an acute phase inflammatory protein in man which
      binds to phosphocholine, chromatin, histones, and the 70-kDa protein of the U1
      small nuclear ribonucleoprotein particle in a calcium-dependent, phosphocholine
      inhibitable manner. CRP also binds to other proteins including fibronectin. The
      determinants involved in CRP binding to these diverse proteins have not been
      identified. The binding of CRP to histones was examined as these proteins are
      available in large quantity at high purity and subject to protease digestion with
      well characterized products. Histone H1 was digested with thrombin and trypsin to
      produce three distinct fragments, N-terminal, central globular, and C-terminal.
      CRP was shown only to bind to the C-terminal fragment. Binding to histone H2A was
      also examined. CRP binding was not diminished by cleavage of the C-terminal
      fragment but was greatly decreased when the central globular region of H2A was
      tested. Peptides were prepared to be identical to the N- and C-terminal fragments
      of H2A. The N-terminal (15 amino acid) fragment of H2A blocked CRP-induced
      precipitation of phosphocholine-coupled bovine serum albumin and histone H2A,
      whereas the C-terminal fragment showed no inhibition. Thus we have defined the
      first reported CRP binding determinant on a protein.

PMID- 1989978
TI  - Metabolism of poly(3-hydroxyalkanoates) (PHAs) by Pseudomonas oleovorans.
      Identification and sequences of genes and function of the encoded proteins in the
      synthesis and degradation of PHA.
AB  - Pseudomonas oleovorans accumulates poly(3-hydroxyalkanoates) (PHAs) after growth
      on medium chain length hydrocarbons. Large amounts of this polyester are
      synthesized when cells are grown under nitrogen-limiting conditions. When
      nitrogen is resupplied in the medium, the accumulated PHA is degraded. In this
      paper, we describe mutants which are defective in the synthesis or in the
      degradation of PHA. These mutants were used to select DNA fragments which encode
      PHA polymerases and a PHA depolymerase. A 25-kilobase (kb) DNA fragment was
      isolated from P. oleovorans that complements a Pseudomonas putida mutant unable
      to accumulate PHA. Subcloning resulted in the assignment of a 6.4-kb EcoRI
      fragment as the pha locus, containing genetic information for PHA synthesis.
      Mutants in the PHA degradation pathway were also complemented by this fragment,
      indicating that genes encoding PHA biosynthetic and degradative enzymes are
      clustered. Analysis of the DNA sequence of the 6.4-kb fragment revealed the
      presence of two open reading frames encoding PHA polymerases based on homology to
      the poly(3-hydroxybutyrate) polymerase from Alcaligenes eutrophus. A third open
      reading frame complemented the PHA degradation mutation and is likely to encode a
      PHA depolymerase. The presence of two PHA polymerases is due to a 2098-base pair
      DNA duplication. The PHA polymerases are 53% identical and show 35-40% identity
      to the poly(3-hydroxybutyrate) polymerase. No clear difference in specificity was
      found for the PHA polymerases. However, with the pha locus cloned on a multicopy
      vector, a polymer was accumulated that contains a significantly higher amount of
      substrate-derived monomers. An increase in the rate of polyester synthesis versus
      oxidation of the monomers in the beta-oxidation explains these findings.

PMID- 1989979
TI  - Regulation of rat adrenal messenger RNA and protein levels for cytochrome P-450s
      and adrenodoxin by dietary sodium depletion or potassium intake.
AB  - The effect of low sodium and high potassium intake on rat adrenal zona
      glomerulosa (ZG) and zona fasciculata-reticularis (ZFR) were studied during a 7
      day period, by analyzing mRNA and protein levels of various enzymes involved in
      aldosterone synthesis. In ZG significant increases in cytochrome P-450scc, P
      450c21, P-450(11 beta), adrenodoxin mRNA and protein levels were observed after 2
      days with either diet, and at day 7 these levels were further increased. The
      largest mRNA induction was observed at day 7 in sodium-depleted rats for P-450(11
      beta), with a 4-fold increase, followed by 2.7- and 2.0-fold increases for P
      450scc and P-450c21, respectively. A pattern similar to those of P-450scc and P
      450(11 beta) was observed for adrenodoxin with a 2.1-fold increase after 7 days
      of Na+ restriction. In K(+)-loaded rats mRNA levels for P-450scc, P-450(11 beta),
      P-450c21, and adrenodoxin were also increased by 2.2-, 2.1-, 1.5-, and 1.9-fold
      respectively. Protein levels of these enzymes were also measured in ZG and showed
      increases similar to those of their respective mRNAs for both treatments. On the
      other hand, mRNA levels of P-450scc, P-450(11 beta), P-450c21, and adrenodoxin in
      ZFR were found significantly lower than in ZG, although they were slightly
      increased for both treated groups of rats as compared with controls. In addition,
      ZFR protein levels of corresponding enzymes did not fluctuate significantly under
      both ionic regimens. In conclusion, both low sodium and high potassium intakes
      act primarily on ZG. Their action on plasma aldosterone seems to be mediated by
      increasing both mRNA and protein and levels of steroidogenic enzymes, especially
      at the early step (cytochrome P-450scc) and even more at the late steps
      (cytochrome P-450(11 beta]. In addition, a close relationship appears to exist
      between the two mitochondrial P-450s and their electron donor adrenodoxin, since
      their mRNA and protein levels were similarly enhanced for both diets used.

PMID- 1989980
TI  - Mutations in the third alpha-helix of bovine growth hormone dramatically affect
      its intracellular distribution in vitro and growth enhancement in transgenic
      mice.
AB  - To investigate the relationship between the secondary structure of the third
      alpha-helix (amino acids 109-126) of bovine growth hormone (bGH) and the
      biological activity of the molecule, proline or glycine residues have been used
      as substitutes for native amino acids at positions 114, 118, 121, and 126,
      respectively. Mutations at the positions 114, 118, and 121 resulted in a dramatic
      decrease in bGH secretion by transiently transfected mouse L cells whereas the
      substitution of glycine for glutamate at position 126 (bGH-E126G) did not affect
      secretion. Immunofluorescence staining revealed that those nonsecretory bGH
      mutations possessed a different intracellular location as compared with wild-type
      bGH or the mutated secretory forms of bGH. Similar results were seen in the
      distribution of these mutated bGH molecules in transfected rat GH-3 cells.
      Transgenic mice that express wild-type bGH or bGH-E126G grew to approximately 1.6
      times the mass of nontransgenic littermates. Transgenic mice that express two
      nonsecretory forms of mutated bGHs were found to lack the enhanced mouse growth
      phenotype in spite of elevated levels of serum bGH. These results suggest that
      the secondary structure in the third alpha-helix of bGH may be important for
      efficient intracellular targeting in vitro and in growth promotion in transgenic
      mice.

PMID- 1989981
TI  - Identification of the site of photocross-linking formed in the absence of
      magnesium nucleotide from SH2 (Cys-697) in myosin subfragment 1 labeled with 4'
      maleimidylbenzophenone.
AB  - The site of photocross-linking between Cys-697 (SH2), prelabeled with 4'
      [14C]maleimidylbenzophenone, and the 50-kDa segment of myosin S1 on irradiation
      in the absence of nucleotide has been determined by isolation of the 20-50-kDa
      adduct and subsequent tryptic proteolysis. Isolation and partial sequencing of
      the radioactively labeled peptide indicate that the site of cross-linking is Arg
      239. This result indicates that, in the absence of nucleotide, Arg-239 resides at
      about 1.0 nm from SH2 and, on the basis of the recent work of Sutoh and Hiratsuka
      (Sutoh, K. and Hiratsuka T. (1988) Biochemistry 27, 2964-2969) places Arg-239 at
      no more than 1.45 nm from either Lys-184 or Lys-189 of the nucleotide-binding
      "glycine-rich" loop prior to the binding of nucleotide.

PMID- 1989982
TI  - Different fate in vivo of oxidatively modified low density lipoprotein and
      acetylated low density lipoprotein in rats. Recognition by various scavenger
      receptors on Kupffer and endothelial liver cells.
AB  - Human low density lipoprotein was oxidized (Ox-LDL) by exposure to 5 microM Cu2+
      and its fate in vivo was compared to acetylated low density lipoprotein (Ac-LDL).
      Ox-LDL, when injected into rats, is rapidly removed from the blood circulation by
      the liver, similarly as Ac-LDL. A separation of rat liver cells into parenchymal,
      endothelial, and Kupffer cells at 10 min after injection of Ox-LDL or Ac-LDL
      indicated that the Kupffer cell uptake of Ox-LDL is 6.8-fold higher than for Ac
      LDL, leading to Kupffer cells as the main liver site for Ox-LDL uptake. In vitro
      studies with isolated liver cells indicated that saturable high affinity sites
      for Ox-LDL were present on both endothelial and Kupffer cells, whereby the
      capacity of Kupffer cells to degrade Ox-LDL is 6-fold higher than for endothelial
      cells. Competition studies showed that unlabeled Ox-LDL competed as efficiently
      (90%) as unlabeled Ac-LDL with the cell association and degradation of 125I
      labeled Ac-LDL by endothelial and Kupffer cells. However, unlabeled Ac-LDL
      competed only partially (20-30%) with the cell association and degradation of
      125I-labeled Ox-LDL by Kupffer cells, while unlabeled Ox-LDL or polyinosinic acid
      competed for 70-80%. It is concluded that the liver contains, in addition to the
      scavenger (Ac-LDL) receptor which interacts efficiently with both Ac-LDL and Ox
      LDL and which is concentrated on endothelial cells, an additional specific Ox-LDL
      receptor which is highly concentrated on Kupffer cells. In vivo the specific Ox
      LDL recognition site on Kupffer cells will form the major protection system
      against the occurrence of the atherogenic Ox-LDL particles in the blood.

PMID- 1989983
TI  - Phosphorylation causes a conformational change in the carboxyl-terminal domain of
      the mouse RNA polymerase II largest subunit.
AB  - The carboxyl-terminal domain (CTD) of the largest subunit of eukaryotic RNA
      polymerase II can be phosphorylated by a p34cdc2/CDC28-containing CTD kinase.
      Phosphorylated serine (or threonine) is located at positions 2 and 5 in the
      repetitive heptapeptide consensus sequence Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7. We
      show here that phosphorylation of the mouse CTD retards its electrophoretic
      mobility in sodium dodecyl sulfate-polyacrylamide gels in a way similar to that
      observed for the II0 form of the largest subunit of RNA polymerase II
      phosphorylated in vivo. At the maximum level of phosphorylation by CTD kinase in
      vitro, there are 15-20 phosphates evenly distributed among the 52 heptapeptide
      repeats that comprise the mouse CTD. Gel filtration chromatography and sucrose
      gradient ultracentrifugation analyses indicate that phosphorylation induces a
      dramatic conformational change in the CTD with the phosphorylated form adopting a
      far more extended structure than the unphosphorylated CTD.

PMID- 1989984
TI  - Interaction of a regulatory protein with a DNA target containing two overlapping
      binding sites.
AB  - The LexA repressor from Escherichia coli regulates the transcription of about 20
      different genes upon binding to single or multiple operators. In this work we
      study the interaction of LexA with the control region of the caa gene (coding for
      the bacterial toxin colicin A) that contains two operators (O1 and O2) which
      overlap by at least 2 base pairs relevant for sequence specific DNA recognition.
      This arrangement raises the question of how the LexA molecules which bind to the
      central overlapping part of the two operators avoid steric clashes and further,
      of whether the interaction of LexA with the two operators is cooperative or not.
      To address these questions we have constructed two mutant operators (O1+O2- and
      O1-O2+) for which the two most strongly conserved base pairs in each of the
      external operator half-sites have been mutated. Using methylation interference
      with the complex formation of LexA with the wild-type and these two mutant
      operators we could show: 1) that the two mutant operators behave symmetrically in
      that the methylation of one crucial guanine base in both operator half-sites
      interferes strongly with complex formation, 2) but that in the wild-type operator
      (containing four functional operator half-sites) only the two external half
      operators give rise to interference if this crucial guanine base is methylated,
      whereas methylation of the two equivalent guanine bases within the two central
      (overlapping) operator half-sites does not lead to interference with the
      formation of a complex where both operators are occupied simultaneously. These
      data suggest that the centrally bound LexA molecules adopt a somewhat different
      binding mode than those bound to the external half-operators in order to avoid
      steric clashes and/or to optimize protein-protein contacts which are likely to be
      at the origin of the binding cooperativity that we could demonstrate by
      quantitative DNase I footprinting and gel retardation experiments. While the
      methylation interference experiments revealed a non-equivalence for the binding
      of externally and centrally bound LexA molecules, both methylation protection and
      hydroxyl radical footprinting were unable to reveal this difference, suggesting
      that the difference between the two binding modes should be fairly subtle.

PMID- 1989985
TI  - Covalent structure, disulfide bonding, and identification of reactive surface and
      active site residues of human prostatic acid phosphatase.
AB  - The pairing of the half-cysteine residues of human prostatic acid phosphatase was
      established by proteolytic digestion and analysis of the resulting peptide
      mixtures by fast atom bombardment mass spectrometry (FAB-MS). An independently
      derived, full length cDNA clone was used as the basis for the interpretation of
      the FAB-MS data. The sequence of the native protein is that predicted from the
      present cDNA sequence, except for the carboxyl-terminal end and some possible
      post-translational deamidations. Isolated human prostatic acid phosphatase was
      found to have multiple carboxyl-terminal ends, terminating in Thr, Glu, and Asp,
      corresponding to residues 349-351 of the 354-residue protein that is predicted
      from the cDNA sequence after removal of a leader peptide. The protein contains no
      free sulfhydryl groups. The identical monomer chains of the dimeric native enzyme
      are found to contain three disulfide bonds, specifically Cys-129 to Cys-340, Cys
      183 to Cys-281, and Cys-315 to Cys-319. In view of the conserved positions of
      cysteines in the homologous human and rat liver lysosomal acid phosphatases, an
      identical disulfide bonding pattern may be predicted for those proteins. The
      location of a potential antigenic site was established by selective labeling of
      proximate tyrosine residues predicted to be on the surface. A conserved RHGXRXP
      sequence is present in the prostatic, lysosomal, Escherichia coli, and yeast acid
      phosphatases and is predicted to be of mechanistic significance. In addition,
      residue Arg-54 is shown to be an active site residue by reaction of the enzyme
      with phenylglyoxal. Interestingly, this residue is present in a sequence RXRY
      (R,H) that is also present in lysosomal phosphatase and in recently described
      protein tyrosine phosphatases.

PMID- 1989986
TI  - Complete primary structure of a galactose-specific lectin from the venom of the
      rattlesnake Crotalus atrox. Homologies with Ca2(+)-dependent-type lectins.
AB  - The complete primary structure of a galactose-specific lectin contained in the
      venom of the rattlesnake, Crotalus atrox, was determined. The lectin is composed
      of two covalently linked, identical subunits, each consisting of 135 amino acid
      residues. Under physiological conditions the lectin proved to be highly
      aggregated. The venom lectin contained 9 half-cystines, 8 of which formed four
      intrasubunit disulfide bridges (Cys3-Cys14, Cys31-Cys131, Cys38-Cys133, and
      Cys106-Cys123), while Cys86 was involved in an intersubunit disulfide bridge.
      Because of the high content of disulfide bridges, the intact lectin was extremely
      resistant to tryptic digestion. The determined amino acid sequence was found to
      be homologous with those of the so-called carbohydrate recognition domains of
      Ca2(+)-dependent-type lectins in animal. Among them, 8 amino acid residues
      (Cys31, Gly69, Trp92, Pro97, Cys106, Asp120, Cys123, and Cys131) were completely
      conserved. Leu40, Trp67, and Trp81 were also well conserved. The rattlesnake
      venom lectin showed high hemagglutinating activity. These results, together with
      the occurrence of similar lectins in crotalid venoms, suggest that these lectins
      have evolved in order to make the venom a more effective weapon to capture prey
      animals.

PMID- 1989987
TI  - Isolation, nucleotide sequence, and disruption of the Saccharomyces cerevisiae
      gene encoding mitochondrial NADP(H)-specific isocitrate dehydrogenase.
AB  - Mitochondrial NADP(H)-specific isocitrate dehydrogenase (IDP1) was purified from
      yeast cells grown with acetate as a carbon source. IDP1 was shown to be a dimer
      with a subunit molecular weight of approximately 45,000. Immunochemical levels of
      IDP1 were found to vary in inverse proportion with those of mitochondrial NAD(H)
      specific isocitrate dehydrogenase in cells grown with glucose or with acetate as
      a carbon source. A 20-residue amino-terminal sequence was obtained for IDP1, and
      degenerate oligonucleotides were used to synthesize a 50-base pair polymerase
      chain reaction product corresponding to the coding region for a portion of the
      amino terminus. The 50-base pair DNA fragment was used as a hybridization probe
      to identify plasmids containing the IDP1 gene in a yeast genomic DNA library. The
      complete nucleotide sequence of the IDP1 coding region was determined and
      translated into a 412-residue amino acid sequence for the mature protein which is
      preceded by a putative 16-residue mitochondrial targeting presequence. A haploid
      yeast strain containing a chromosomal disruption of the IDP1 locus was
      constructed and found to be capable of growth with glucose but not with other
      carbon sources, suggesting that IDP1 provides a critical function and may be the
      primary source of NADPH in yeast mitochondria.

PMID- 1989988
TI  - Casein kinase II. cDNA sequences, developmental expression, and tissue
      distribution of mRNAs for alpha, alpha', and beta subunits of the chicken enzyme.
AB  - We report the complete primary structures, as deduced from cloned cDNAs, of two
      catalytic (alpha and alpha') and one beta subunit of chicken casein kinase II.
      The alpha and alpha' subunits are closely related to each other but differ in
      their carboxyl termini; moreover, minor differences are distributed throughout
      the entire lengths of the two proteins, indicating that they are derived from
      separate genes. Comparison of the chicken protein sequences with those of their
      mammalian homologs reveals a high degree of evolutionary conservation of all
      three subunits. Northern analyses were carried out to study the expression of
      casein kinase II subunits during chicken embryonic development as well as in
      adult tissues. A single transcript migrating at 1 kilobase was detected when
      using a beta-specific probe, but multiple transcripts ranging in size from 1.45
      to 2.8 kilobase were revealed by alpha- and alpha'-specific probes. Expression of
      mRNA for all three subunits was high in early embryos but decreased substantially
      during embryonic development. A comparative analysis of casein kinase II
      expression in different adult tissues revealed two major findings. First,
      relative levels of expression of the two catalytic subunits displayed a
      pronounced tissue specificity, consistent with the possibility that alpha and
      alpha' subunits may carry out specialized functions. Second, no correlation was
      observed between levels of transcripts for the catalytic subunits and those of
      mRNA for the beta subunit.

PMID- 1989989
TI  - Insulin induction of ornithine decarboxylase. Importance of mRNA secondary
      structure and phosphorylation of eucaryotic initiation factors eIF-4B and eIF-4E.
AB  - We investigated the possibility that insulin could stimulate translation of
      ornithine decarboxylase (ODC) mRNA in a murine fibroblast cell line that
      expresses large numbers of human insulin receptors (HIR 3.5 cells). Within 3 h
      after exposure to 70 nM insulin, ODC enzyme activity increased approximately 50
      fold and mRNA accumulation 3-fold in the HIR 3.5 cells but not in normal
      fibroblasts. Pretreatment of cells with cycloheximide completely inhibited
      insulin-stimulated ODC expression; actinomycin D partially inhibited this effect.
      To determine the influence of the 5' untranslated region (5'UTR) of ODC mRNA on
      insulin-regulated ODC expression, plasmids were constructed which contained
      sequences from the 5'UTR of a rat ODC mRNA interposed between the ferritin
      promoter and the coding region of the human growth hormone gene. These
      constructions were then expressed transiently in HIR 3.5 cells. Insulin
      stimulated a 2-4-fold change in growth hormone accumulation in the medium of
      cells transiently expressing plasmids containing the entire 5'UTR of ODC mRNA or
      just the 5'-most 115 bases, a G/C-rich conserved sequence predicted to form a
      stem-loop structure and shown previously to be responsible for constitutive
      inhibition of translation. There was a direct correlation between the extent of
      insulin stimulation and the predicted secondary structure of the added 5'UTR
      sequences. To determine whether this effect might be due to insulin activation of
      initiation factors responsible for melting mRNA secondary structure, we examined
      the effect of insulin on the phosphorylation states of two such factors,
      eucaryotic initiation factors eIF-4B and eIF-4E. Insulin stimulated the
      phosphorylation of both initiation factors; this stimulation was evident at 15
      min and maximal by 60 min. These results suggest a potential general mechanism by
      which insulin could preferentially stimulate translation of mRNAs whose 5'UTRs
      exhibit significant secondary structure by activating initiation factors involved
      in melting such secondary structures.

PMID- 1989990
TI  - Evolution of the insulin gene superfamily. Sequence of a preproinsulin-like
      growth factor cDNA from the Atlantic hagfish.
AB  - Complementary DNAs encoding a preproinsulin-like growth factor (prepro-IGF) have
      been cloned from a primitive vertebrate species, the Atlantic hagfish, by using a
      DNA amplification strategy based on the polymerase chain reaction. A composite
      sequence containing a 414-nucleotide open reading frame encoding 138 amino acids
      and 164 nucleotides in the 3'-untranslated region was obtained. The deduced
      partial sequence of hagfish prepro-IGF reveals that it is organized like the
      mammalian prepro-IGFs with an unusually large (greater than 39-amino acid) signal
      peptide (initiator methionine residue is missing), 29-amino acid B, 15-amino acid
      C, 21-amino acid A, 10-amino acid D, and 26-amino acid E domains. All the
      invariant residues necessary to form the correct tertiary fold of an insulin-like
      molecule have been conserved in hagfish IGF. Sequence comparisons revealed that
      the A and B domains of hagfish IGF are equally similar to those of human IGF-I
      (35 out of 50 amino acids) or IGF-II (37 out of 53 amino acids). In contrast, the
      similarity between hagfish and mammalian pro-IGFs in the C, D, and E domains is
      relatively low. Northern blot analysis of RNA isolated from hagfish brain, heart,
      liver, skeletal muscle, and islet organ, however, indicated that hagfish IGF,
      like mammalian IGF-I, is expressed predominantly in the liver as a 4.2-kilobase
      transcript. DNA blot analysis revealed that hagfish IGF is a single copy gene.
      The predicted sequence of hagfish prepro-IGF thus demonstrates that the
      divergence of the IGF and insulin genes occurred prior to the separation of the
      Agnatha and that the organization and tertiary structure of IGF have been well
      maintained throughout 550 million years of vertebrate evolution.

PMID- 1989991
TI  - Agonist-regulated phosphorylation of the pancreatic cholecystokinin receptor.
AB  - The present study was undertaken to determine if the cholecystokinin (CCK)
      receptor may be phosphorylated, and to gain insight into its regulation. For
      this, the ATP pool of rat pancreatic acini was prelabeled with 32P, and the cells
      were stimulated with various secretagogues. CCK receptors from treated cells were
      enriched by sequential fractionation to produce plasmalemma, and subsequent
      solubilization and lectin-affinity chromatography. This protocol detected a
      phosphorylated Mr = 85,000-95,000 plasma membrane glycoprotein with features
      similar to the CCK receptor. Phosphorylation of this protein occurred rapidly
      (less than 2 min) and in a concentration-dependent manner in response to CCK, and
      was inhibited by the CCK receptor antagonist L-364,718. Further evidence that
      this represented the CCK receptor included comigration of phosphorylated and CCK
      radioligand affinity-labeled proteins on sodium dodecyl sulfate-polyacrylamide
      gels, both in native forms and after endoglycosidase F deglycosylation, and the
      specific adsorption of the phosphoprotein to a CCK analogue affinity resin.
      Phosphorylation occurred predominantly on serine residues of the receptor
      protein. Phosphorylation of this protein was also enhanced in response to other
      secretagogues which, like CCK, stimulate a cascade leading to protein kinase C
      activation, and in response to direct activation of this enzyme by 12-O
      tetradecanoylphorbol 13-acetate. Thus, the pancreatic CCK receptor is
      phosphorylated in a regulated manner, in response to both homologous and
      heterologous secretagogues, and to protein kinase C activation.

PMID- 1989992
TI  - Mechanisms of neuronal adaptation to ethanol. Ethanol induces Hsc70 gene
      transcription in NG108-15 neuroblastoma x glioma cells.
AB  - The mechanisms underlying neuronal adaptation to ethanol are poorly understood
      but appear to involve alterations in cellular membrane structure and/or function.
      Using a two-dimensional gel analysis, we have recently identified Hsc70 as an
      ethanol-responsive gene (Miles, M.F. (1989) Neurology 39, (Suppl. 1), 425). Hsc70
      is a constitutive member of the 70-kDa stress protein family which plays an
      important role in protein trafficking and coated vesicle processing. Thus,
      modulation of Hsc70 by ethanol could produce widespread changes in cellular
      membrane functioning. Here, we report a detailed study on the regulation of Hsc70
      by ethanol in NG108-15 neuroblastoma x glioma cells. Northern and Western blot
      analyses showed that ethanol concentrations observed in actively drinking
      alcoholics caused an induction of Hsc70 mRNA and protein. Increases in Hsc70 mRNA
      were seen as early as 4 h after exposure to ethanol. In comparison with ethanol,
      propanol and butanol caused proportionally greater increases in Hsc70 mRNA. This
      is consistent with known anesthetic and intoxicating potencies of these aliphatic
      alcohols and suggested that lipophilicity, rather than an osmotic effect, was
      critical for ethanol induction of Hsc70. Induction of Hsc70 mRNA by ethanol
      resulted, at least in part, from increased Hsc70 gene transcription as determined
      by nuclear runoff studies. Stable transfection analysis revealed an ethanol
      responsive cis-acting element in the proximal 2500 base pairs of the Hsc70
      promoter. Regulation of Hsc70 by 50-200 mM ethanol appeared to be a specific
      change in expression of an ethanol-responsive gene rather than a typical stress
      protein response since no induction of the highly inducible stress protein,
      Hsp70, was seen at these ethanol concentrations. These results suggest that
      ethanol-induced changes in Hsc70 transcription may be important for neuronal
      adaptation to ethanol and the development of tolerance and dependence in
      alcoholics.

PMID- 1989993
TI  - Antimitogenic and mitogenic actions of interleukin-1 in diverse cell types are
      associated with induction of gro gene expression.
AB  - Interleukin-1 (IL-1) is an antiproliferative factor for growing human melanoma
      A375-C6 cells. To define the molecular basis for the action of IL-1, we set out
      to identify early genes induced by the cytokine in the absence of de novo protein
      synthesis. cDNA libraries were constructed from A375-C6 cells that were exposed
      or unexposed to IL-1 plus cycloheximide. Subtractive hybridization was used to
      prepare a library that was enriched for IL-1-induced clones. Two of these clones
      were shown by Northern analysis to represent IL-1-inducible genes. Nucleotide
      sequencing identified these genes as gro/melanoma growth stimulatory activity,
      which encodes a cell secretory product, and c-jun, which encodes a transcription
      factor. IL-1 caused persistent steady state elevation of gro mRNA but only
      transient induction of c-jun. Northern analysis using gene probes for the
      transcription factors c-fos and Egr-1 revealed that IL-1 induced c-fos but not
      Egr-1 expression in these cells. This indicates that differential early gene
      expression characterizes the growth-inhibitory action of IL-1. In contrast,
      serum, which is mitogenic for these cells, induces c-jun, c-fos, and Egr-1, but
      not gro expression. These data imply that in A375-C6 cells, both growth
      inhibitory and stimulatory signals can channel their action through c-fos and c
      jun genes. As gro induction was specifically associated with the antimitogenic
      action of IL-1, we studied the effect of the cytokine on gro gene expression in
      other types of cells. IL-1 was mitogenic for human glioblastoma and monkey kidney
      epithelial cells and induced gro whereas other mitogens did not. Thus, IL-1 can
      induce gro gene expression in diverse cell types, whether it acts to stimulate or
      inhibit proliferation. Like other cytokines gro may play diverse cell-specific
      roles in growth control.

PMID- 1989994
TI  - Structural requirements for Ca2+ binding to the gamma-carboxyglutamic acid and
      epidermal growth factor-like regions of factor IX. Studies using intact domains
      isolated from controlled proteolytic digests of bovine factor IX.
AB  - Blood coagulation factor IX is composed of discrete domains with an NH2-terminal
      vitamin K-dependent gamma-carboxyglutamic acid (Gla)-containing region, followed
      by two domains that are homologous with the epidermal growth factor (EGF)
      precursor and a COOH-terminal serine protease part. Calcium ions bind to the Gla
      containing region and to the NH2-terminal EGF-like domain. To be able to
      determine the structure and function of the Gla- and EGF-like domains, we have
      devised a method for cleaving factor IX under controlled conditions and isolating
      the intact domains in high yield, either separately or linked together. The Ca2+
      and Mg2+ binding properties of these fragments were examined by monitoring the
      metal ion-induced changes in intrinsic protein fluorescence. A fragment,
      consisting of the Gla region linked to the two EGF-like domains, bound Ca2+ in a
      manner that was indistinguishable from that of the intact molecule, indicating a
      native conformation. The Ca2+ affinity of the isolated Gla region was lower,
      suggesting that the EGF-like domains function as a scaffold for the folding of
      the Gla region. The Gla-independent high affinity metal ion binding site in the
      NH2-terminal EGF-like domain was shown to bind Ca2+ but not Mg2+. A comparison
      with similar studies of factor X (Persson, E., Bjork, I., and Stenflo, J. (1991)
      J. Biol. Chem. 266, 2444-2452) suggests that the Ca2(+)-induced fluorescence
      quenching is due to an altered environment primarily around the tryptophan
      residue in position 42.

PMID- 1989995
TI  - The epidermal growth factor-like domains of factor IX. Effect on blood clotting
      and endothelial cell binding of a fragment containing the epidermal growth factor
      like domains linked to the gamma-carboxyglutamic acid region.
AB  - The binding of factor IX to cultured bovine endothelial cells was characterized
      using isolated domains of bovine factor IX. An NH2-terminal fragment that
      consists of the gamma-carboxyglutamic acid (Gla) region linked to the two
      epidermal growth factor (EGF)-like domains bound to the endothelial cells with
      the same affinity as intact factor IX, indicating that the serine protease part
      of factor IX is not involved in binding. This fragment also inhibited the factor
      IXa beta'-induced clotting of plasma at a concentration that would suggest a
      competition for phospholipid binding sites. However, after proteolytic removal of
      the Gla region from the fragment, the two EGF-like domains inhibited clotting
      almost as effectively, suggesting a direct interaction between this part of the
      molecule and the cofactor, factor VIIIa. Using affinity-purified Fab fragments
      against the Gla region, the EGF-like domains, and the serine protease part, it
      was observed that the serine protease part of the molecule undergoes a large
      conformational change upon activation, whereas the Gla region and the EGF-like
      domains appear to be unaffected. All three classes of Fab fragments were equally
      efficient as inhibitors of the factor IXa beta'-induced clotting reaction. Part
      of factor Va and factor VIIIa have significant sequence homology to a lectin. We
      therefore investigated the effect on in vitro clotting of the recently identified
      unique disaccharide Xyl alpha 1-3Glc, that is O-linked to a serine residue in the
      NH2-terminal EGF-like domain of human factor IX (Hase, S., Nishimura, H.,
      Kawabata, S.-I., Iwanaga, S., and Ikenaka, T. (1990) J. Biol. Chem. 265, 1858
      1861). However, no effect on blood clotting was observed in the assay system
      used. Our results are compatible with a model in which the serine protease part
      provides the specificity of the binding of factor IXa to factor VIIIa
      phospholipid, but that the EGF-like domain(s) also contributes to the interaction
      of the enzyme with its cofactor.

PMID- 1989996
TI  - Protein structural requirements for Ca2+ binding to the light chain of factor X.
      Studies using isolated intact fragments containing the gamma-carboxyglutamic acid
      region and/or the epidermal growth factor-like domains.
AB  - Coagulation factor X is a multidomain proenzyme of a serine protease. Calcium
      ions bind to the vitamin K-dependent gamma-carboxyglutamic acid (Gla) residues
      and to a site in the NH2-terminal of two epidermal growth factor (EGF)-like
      domains. To study structure-function relationships in the NH2-terminal part of
      factor X and to determine the structure of isolated domains, we have developed
      methods that allow the subsequent isolation of the first or both EGF-like domains
      with or without an attached Gla domain from controlled proteolytic digests of the
      protein. The Ca2(+)-induced changes of the intrinsic protein fluorescence were
      measured to elucidate whether the isolated fragments retain their native
      conformation. Changes in the fluorescence caused by Ca2+ binding were found to
      result from perturbations of the environment of the Trp residue in position 41.
      Calcium ion binding to the Gla-containing region linked to the NH2-terminal EGF
      like domain was identical with that to intact factor X, indicating a native
      orientation of the ligand binding groups in the fragment. In contrast, the
      isolated Gla peptide had a lower affinity for Ca2+, suggesting that the NH2
      terminal EGF-like domain serves as a scaffold for the folding of the Gla region.
      Similarly, the presence of the Gla region was found to increase the affinity of
      the Gla-independent site in the first EGF-like domain for Ca2+. The metal ion
      induced resistance against chymotryptic cleavage COOH-terminal of Tyr-44 in
      intact factor X is similar in the isolated fragment that contains the Gla region
      linked to one EGF-like domain, indicating a native conformation of the fragment
      in the presence of Ca2+. Furthermore, the Gla-independent metal ion binding site
      binds Ca2+ but does not appear to bind Mg2+.

PMID- 1989997
TI  - The gamma-carboxyglutamic acid and epidermal growth factor-like domains of factor
      X. Effect of isolated domains on prothrombin activation and endothelial cell
      binding of factor X.
AB  - Factor Xa is the enzymatically active constituent of the prothrombinase complex,
      which catalyzes the conversion of prothrombin to thrombin. We have isolated
      fragments, from tryptic digests of factor X, that consists of the gamma
      carboxyglutamic acid (Gla) region linked to one or two epidermal growth factor
      (EGF)-like domains. Calcium ion binding measurements indicated that these
      fragments have a native conformation. The factor X-GlaEGF fragments inhibit
      factor Xa-induced blood clotting in a manner suggesting that they compete with
      factor Xa for phospholipid binding sites. The same conclusion was reached when
      thrombin generation was studied in a system of purified components (factor Xa,
      factor Va, prothrombin, phospholipid, and Ca2+). There was no evidence for a
      strong interaction between the EGF-like domains of factor Xa and factor Va in
      either system. However, experiments in the purified system without phospholipid
      indicated a direct, albeit weak, interaction between the Gla region of factor Xa
      and factor Va and between the COOH-terminal EGF-like domain of factor Xa and
      factor Va. Using domain-specific Fab fragments, we have confirmed that the
      conformation of the serine protease region alters dramatically upon activation of
      factor X. Furthermore, we have demonstrated that the conformation of the Gla
      region is affected by the activation, whereas the EGF-like domains appear to be
      unaltered. The association constant for factor X binding to endothelial cells was
      two orders of magnitude lower than that for binding of factor IX to these cells.
      Binding of the Gla and GlaEGF fragments suggested Gla-mediated binding to
      phospholipid rather than binding to a specific receptor.

PMID- 1989998
TI  - Preliminary characterization of a cloned neutral isoelectric form of the human
      peptidyl prolyl isomerase cyclophilin.
AB  - We report the cloning of a neutral isoelectric form of the human peptidyl prolyl
      isomerase, cyclophilin, its expression in Escherichia coli, and its purification
      and comparison to bovine thymus cyclophilin. The cloned protein exhibited a pI of
      approximately 7.8 and formed a simple 1:1 complex with cyclosporin A. This cloned
      form had a pI similar to that observed for the neutral isoform (pI approximately
      7.4) of human splenocyte cyclophilin. The bovine thymus proteins exhibited
      anomalous behavior on CM-cellulose chromatography but were resolved into alkaline
      (pI approximately 9.3) isoforms and a new neutral (pI approximately 7.8) isoform
      by isoelectric focusing gel electrophoresis and ultimately into at least four
      discrete isoforms by capillary electrophoresis. For cyclosporin A binding we
      observe a Kd of approximately 160 nM for an electrophoretically heterogeneous
      preparation of the natural bovine protein and approximately 360 nM for the more
      homogeneous preparation of the cloned human neutral isoform. Stopped-flow
      measurements of the activation energies for peptidyl-prolyl isomerase activity
      indicate the recombinant human protein has an activation enthalpy of 3.67
      kcal/mol and an activation entropy of -47.3 cal/K-mol for cis----trans
      isomerization.

PMID- 1989999
TI  - Purification and cDNA-derived sequence of adenylosuccinate synthetase from
      Dictyostelium discoideum.
AB  - Adenylosuccinate synthetase (IMP:L-aspartate ligase (GDP), EC 6.3.4.4) plays an
      important role in purine biosynthesis catalyzing the GTP-dependent conversion of
      IMP to AMP. The enzyme was purified from the cytosol of Dictyostelium discoideum
      using GTP-agarose chromatography as the critical step. It has an apparent
      molecular mass of 44 kDa. Monoclonal antibodies identified several forms of the
      enzyme with pI values between 8.1 and 9.0. Michaelis-Menten constants (Km) were
      low for the nucleotide substrates IMP (Km = 30 microM) and GTP (Km = 35 microM)
      as compared with the value for aspartic acid (Km = 440 microM). These values are
      in good agreement with constants reported from other organisms. Immunological
      studies indicated that the protein is predominantly localized in the cytosol and
      only partially associated with particulate fractions. The enzyme is present
      throughout the developmental cycle of D. discoideum. Using monoclonal antibodies,
      the gene was cloned from a lambda gt11 expression library. The complete sequence
      represents the first reported primary structure of an eucaryotic adenylosuccinate
      synthetase. Southern blots hybridized with a cDNA probe demonstrate that
      adenylosuccinate synthetase is encoded by a single gene and contains at least one
      intron. The deduced amino acid sequence shows 43% identity to adenylosuccinate
      synthetase from Escherichia coli. Homologous regions include short sequence
      motifs, such as the glycine-rich loop which is typical for GTP-binding proteins.

PMID- 1990000
TI  - Molecular cloning of a cDNA and a gene encoding an immunomodulatory protein, Ling
      Zhi-8, from a fungus, Ganoderma lucidum.
AB  - A large amount of the novel immunomodulatory protein Ling Zhi-8 (LZ-8) is
      synthesized in the mycelia of Ganoderma lucidum (Kino, K., Yamashita, A.,
      Yamaoka, K., Watanabe, J., Tanaka, S., Ko, K., Shimizu, K., and Tsunoo, H. (1989)
      J. Biol. Chem. 264, 472-478). A cDNA and a gene for LZ-8 were isolated and
      characterized. The mixed oligonucleotide probes for LZ-8 cDNA were designed from
      the results of protein sequencing (Tanaka, S., Ko, K., Kino, K., Tsuchiya, K.,
      Yamashita, A., Murasugi, A., Sakuma, S., and Tsunoo, H. (1989) J. Biol. Chem.
      264, 16372-16377) and were used for screening the mycelial cDNA library. The
      nucleotide sequence of the cloned cDNA confirms the amino acid sequence of LZ-8
      that was previously determined by protein sequencing. The clones containing the
      LZ-8 gene (lz-8) were obtained from the mycelial genomic DNA library using the
      cDNA probe. Two CCAAT-like sequences and one TATA box were found at the upstream
      region of the postulated transcription initiation site of lz-8. A small intron
      (61 nucleotides long) divided lz-8 into two exons at the 5'-untranslated region.
      The other characteristic sequences were also found around the postulated
      transcription initiation site and around the poly(A) additional site.

PMID- 1990001
TI  - Tyrosine 65 is photolabeled by 8-azidoadenine and 8-azidoadenosine at the NAD
      binding site of diphtheria toxin.
AB  - 8-Azidoadenine and 8-azidoadenosine, two photoactivatable derivatives of adenine
      and adenosine, are competitive inhibitors of diphtheria toxin of similar potency
      with respect to their parent compounds. On irradiation, the two tritium-labeled
      photoactivatable azidoadenines bind covalently and specifically to an enzymic
      fragment of diphtheria toxin that is known to bind to NAD. This photolabeling is
      protected by the enzyme substrate NAD. The radiolabeled protein was fragmented,
      and the radioactive fragments were sequenced. Tyr-65 is labeled specifically by
      both photoreagents, and its labeling was reduced strongly when NAD was present
      during irradiation. Labeling is also reduced strongly by adenine, adenosine, and
      nicotinamide. These results suggest that Tyr-65 is at the NAD binding site of
      diphtheria toxin and that the competitive inhibitors adenine, adenosine, and
      nicotinamide bind to the same portion of the catalytic center of the toxin.

PMID- 1990002
TI  - Resolution of branched DNA substrates by T7 endonuclease I and its inhibition.
AB  - Endonuclease I is a multipurpose enzyme implicated in the breakdown of host DNA,
      packaging of phage DNA, and recombination during the lytic cycle of bacteriophage
      T7. We investigate here some aspects of the substrate requirements for its
      activity in resolving branched intermediates similar to Holliday junctions
      (Holliday, R. (1964) Genet. Res. 5, 282-304) that arise in recombination. The
      enzyme is able to resolve branched substrates containing very short duplex arms:
      4 base pairs suffice. It cleaves 5' to the branch, with a distinct preference for
      the non-crossover strands in Holliday-like model junctions. Ligands that interact
      strongly with the branch site can inhibit the enzyme, with KI values in the 10-50
      microM range.

PMID- 1990003
TI  - Purification and characterization of the Saccharomyces cerevisiae mitochondrial
      leucyl-tRNA synthetase.
AB  - We have purified the product of the NAM2 gene, the mitochondrial leucyl-tRNA
      synthetase, from yeast mitochondria. The purified protein cross-reacts with
      antibodies raised against the product of a LacZ/NAM2 gene fusion and antibodies
      raised against the purified Escherichia coli leucyl-tRNA synthetase. The mass as
      determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis is about
      100 kDa, consistent with the size predicted by the gene sequence (102 kDa). The N
      terminal sequence of the protein has been determined and shows that the first
      nine amino acids predicted by the gene sequence have been removed, probably
      during transport into the mitochondria.

PMID- 1990004
TI  - Two glutamyl-tRNA reductase activities in Escherichia coli.
AB  - delta-Aminolevulinic acid (ALA) is the first committed precursor for tetrapyrrole
      biosynthesis. ALA formation in Escherichia coli occurs in a tRNA-dependent three
      step conversion from glutamate. Glu-tRNA reductase is the key enzyme in this
      pathway. E. coli K12 contains two Glu-tRNA reductase activities which differ in
      their molecular weights. Here we describe the purification of one of these
      enzymes. Four different chromatographic separations yielded a nearly homogeneous
      protein. Its apparent molecular mass under denaturing (sodium dodecyl sulfate
      polyacrylamide gel electrophoresis) and nondenaturing conditions (rate zonal
      sedimentation and gel filtration) is 85,000 +/- 5,000 Da. This indicates a
      monomeric structure for the active enzyme. Gel filtration and glycerol gradient
      centrifugation indicate that the other activity has a molecular mass of 45,000 +/
      5,000 Da. In the presence of NADPH both enzyme activities converted E. coli Glu
      tRNA(2Glu) to glutamate 1-semialdehyde. Addition of GTP or hemin did not affect
      the reductase activity. Both enzymes display sequence-specific recognition of
      tRNA; E. coli Glu-tRNA(2Glu) is a good substrate while the Chlamydomonas
      reinhardtii, Bacillus subtilis, and Synechocystis Glu-tRNA(Glu) species are
      poorly recognized.

PMID- 1990005
TI  - In vitro methylation of the promoter and enhancer of Pro alpha 1(I) collagen gene
      leads to its transcriptional inactivation.
AB  - We created pCOL-KT, a plasmid construct in which the promoter/enhancer of human
      Pro alpha 1(I) gene is linked to the chloramphenicol acetyl transferase reporter
      gene. The Pro alpha 1(I) promoter/enhancer in pCOL-KT was methylated in vitro and
      tested for transcriptional activity by transient expression analysis. Methylation
      of the construct with bacterial methylases reduced transcriptional activity about
      25-fold. Site-specific methylation of eight potential canonical sites of
      eukaryotic methylation within the promoter greatly reduced transcriptional
      activity. Chromatin conformation of the transfected pCOL-KT DNA was analyzed by
      nuclease sensitivity. Although both methylated and unmethylated transfected DNA
      had increased susceptibility to DNase I compared with the endogenous gene, the
      methylated transfected DNA showed increased resistance to nuclease when compared
      with unmethylated transfected DNA, indicating that the methylation of the DNA
      alters the chromatin conformation. We also tested the ability of a human
      rhabdomyosarcoma cell line that does not express type I collagen to support
      transcription from an exogenously added Pro alpha 1(I) promoter/enhancer. The
      transformed cell line is able to support transcription from the Pro alpha 1(I)
      promoter/enhancer. Treatment of the transformed cell line with 5-azacytidine, a
      potent inhibitor of DNA methylation, resulted in transcriptional activation of
      the Pro alpha 1(I) gene. These findings, along with the extreme methylation
      sensitivity of the Pro alpha 1(I) promoter and enhancer, suggest that DNA
      methylation may be an important mechanism of transcriptional inactivation of
      interstitial collagen genes.

PMID- 1990006
TI  - Thermostable aspartate aminotransferase from a thermophilic Bacillus species.
      Gene cloning, sequence determination, and preliminary x-ray characterization.
AB  - The gene encoding aspartate aminotransferase of a thermophilic Bacillus species,
      YM-2, has been cloned and expressed efficiently in Escherichia coli. The primary
      structure of the enzyme was deduced from nucleotide sequences of the gene and
      confirmed mostly by amino acid sequences of tryptic peptides. The gene consists
      of 1,176 base pairs encoding a protein of 392 amino acid residues; the molecular
      mass of the enzyme subunit is estimated to be 42,661 daltons. The active site
      lysyl residue that binds the coenzyme, pyridoxal phosphate, was identified as Lys
      239. Comparison of the amino acid sequence with those of aspartate
      aminotransferases from other organisms revealed very low overall similarities (13
      14%) except for the sequence of the extremely thermostable enzyme from Sulfolobus
      solfataricus (34%). Several amino acid residues conserved in all the compared
      sequences include those that have been reported to participate in binding of the
      coenzyme in three-dimensional structures of the vertebrate and E. coli enzymes.
      However, the strictly conserved arginyl residue that is essential for binding of
      the distal carboxyl group of substrates is not found in the corresponding region
      of the sequences of the thermostable enzymes from the Bacillus species and S.
      solfataricus. The Bacillus aspartate aminotransferase has been purified from the
      E. coli clone cell extracts on a large scale and crystallized in the buffered
      ammonium sulfate solution by the hanging drop method. The crystals are monoclinic
      with unit cell dimensions a = 121.2 A, b = 110.5 A, c = 81.8 A, and beta = 97.6
      degrees, belonging to space group C2, and contain two molecules in the asymmetric
      unit. The crystals of the enzyme-alpha-methylaspartate complex are isomorphous
      with those without the substrate analog.

PMID- 1990007
TI  - Alpha-aminoadipate and kynurenine aminotransferase activities from rat kidney.
      Evidence for separate identity.
AB  - alpha-Aminoadipate aminotransferase and kynurenine aminotransferase activities
      from rat kidney are reportedly associated with the same protein. We observed that
      when the supernatant fraction was maintained at pH 4.5 for 75 min, 100% of
      kynurenine aminotransferase activity was lost, whereas only 40% of aminoadipate
      aminotransferase activity was lost. We purified alpha-aminoadipate
      aminotransferase and kynurenine aminotransferase from rat kidney supernatant
      fraction to electrophoretic homogeneity by ammonium sulfate fractionation, DEAE
      Sephacel, and hydroxylapatite chromatography. Kynurenine aminotransferase
      activity was precipitated by pH treatment. The remaining aminoadipate
      aminotransferase activity was concentrated and injected into rabbits to raise
      antibodies that were used to prepare an affinity column. A mixture of
      aminoadipate aminotransferase and kynurenine aminotransferase activities obtained
      after hydroxylapatite chromatography was subjected to affinity chromatography.
      Aminoadipate aminotransferase and kynurenine aminotransferase activities resolved
      as separate peaks, providing evidence that the two activities are associated with
      two different proteins.

PMID- 1990008
TI  - Control of transcription of the chicken progesterone receptor gene. In vitro and
      in vivo studies.
AB  - To study the promoter of the chicken progesterone receptor (cPR) gene and the
      relevance of several progestin-responsive elements therein, chimeric genes were
      constructed which contained the 5'-flanking region of the cPR gene linked to
      promoterless globin or chloramphenicol acetyltransferase sequences. Cell-specific
      initiation of transcription was observed in transiently transfected chicken
      embryo fibroblasts when using 876 base pairs of the cPR gene upstream region.
      Transcription from these reporter genes could be induced by progestins in the
      presence of cPR form A but not of form B. In keeping with these data, three in
      vitro progesterone receptor (PR)-binding sites were identified in the cPR
      promoter region by DNase I protection assays. However, in vivo, nuclear run-on
      transcription demonstrated that neither primary stimulation with progestins, nor
      treatment of secondarily estrogen-stimulated chicks with progestins,
      glucocorticoids, or androgens resulted in any significant change of cPR gene
      transcription in the oviduct, thus suggesting a cell- and/or development-specific
      role for these progestin-responsive elements. Although estrogen is known to
      increase PR levels in the chick oviduct, this effect does not involve stimulation
      of PR gene transcription, as demonstrated here by nuclear run-on experiments, the
      analysis of DNase I hypersensitive sites, and transient cotransfection studies.
      Since acute withdrawal from estrogen-stimulation markedly decreased the level of
      cPR mRNAs in chick oviduct when analyzed by Northern blotting, we conclude that
      estrogen-dependent stimulation of PR levels in the oviduct is a post
      transcriptional process.

PMID- 1990009
TI  - The effects of different cysteine for glycine substitutions within alpha 2(I)
      chains. Evidence of distinct structural domains within the type I collagen triple
      helix.
AB  - Affected individuals from two apparently distinct, mild osteogenesis imperfecta
      families were heterozygous for a G to T transition in the COL1A2 gene that
      resulted in cysteine for glycine substitutions at position 646 in the alpha 2(I)
      chain of type I collagen. A child with a moderately severe form of osteogenesis
      imperfecta was heterozygous for a G to T transition that resulted in a
      substitution of cysteine for glycine at position 259 in the COL1A2 gene. Type I
      collagen molecules containing an alpha 2(I) chain with cysteine at position 259
      denaturated at a lower temperature than molecules containing an alpha 2(I) chain
      with cysteine at position 646. In contrast to cysteine for glycine substitutions
      in the alpha 1(I) chain, the severity of the osteogenesis imperfecta phenotype is
      not directly proportional to the distance of the mutation from the amino-terminal
      end of the triple helix. These findings could be explained if the type I collagen
      triple helix contains discontinuous domains that differ in their contributions to
      maintaining helix stability.

PMID- 1990010
TI  - Differential regulation of the GLUT-1 and GLUT-4 glucose transport systems by
      glucose and insulin in L6 muscle cells in culture.
AB  - The regulation by glucose and insulin of the muscle-specific facilitative glucose
      transport system GLUT-4 was investigated in L6 muscle cells in culture. Hexose
      transport activity, mRNA expression, and the subcellular localization of the GLUT
      4 protein were analyzed. As observed previously (Walker, P. S., Ramlal, T.,
      Sarabia, V., Koivisto, U.-M., Bilan, P. J., Pessin, J. E., and Klip, A. (1990) J.
      Biol. Chem. 265, 1516-1523), 24 h of glucose starvation and 24 h of insulin
      treatment each increase glucose transport activity severalfold. Here we report a
      differential regulation of the GLUT-4 and GLUT-1 transport systems under these
      conditions. (a) The level of GLUT-4 mRNA was not affected by glucose starvation
      and was diminished by prolonged (24 h) administration of insulin; in contrast,
      the level of GLUT-1 mRNA was elevated under both conditions. (b) Glucose
      starvation and prolonged insulin administration increased the amount of both GLUT
      4 and GLUT-1 proteins in the plasma membrane. (c) In intracellular membranes,
      glucose starvation elevated, and prolonged insulin administration reduced, the
      GLUT-4 protein content. In contrast, the GLUT-1 protein content in these
      membranes decreased with glucose starvation and increased with insulin treatment.
      Glucose transport was rapidly curbed upon refeeding glucose to glucose-starved
      cells, with half-maximal reversal after 30 min and maximal reversal after 4 h.
      This was followed by a marked decrease in the levels of GLUT-1 mRNA without major
      changes in GLUT-4 mRNA. Neither 2-deoxy-D-glucose nor 3-O-methyl-D-glucose could
      substitute for D-glucose in these effects. It is proposed that glucose and
      insulin differentially regulate the two glucose transport systems in L6 muscle
      cells and that the rapid down-regulation of hexose transport activity by glucose
      is regulated by post-translational mechanisms.

PMID- 1990011
TI  - Bovine glomerular basement membrane. Location and structure of the asparagine
      linked oligosaccharide units and their potential role in the assembly of the 7 S
      collagen IV tetramer.
AB  - Collagen IV contains an amino-terminal tetramerization domain (7 S) that is
      involved in aggregation and cross-linking as part of the process of self-assembly
      of the collagen IV matrix of basement membranes. We determined the structure and
      location of the Asn-linked oligosaccharides of the 7 S tetramer. Two
      glycopeptides, GP-1 and GP-2, were isolated from tryptic digests of the 7 S
      tetramer and were characterized. GP-1 and GP-2 are derived from the alpha 1(IV)
      chain and the alpha 2(IV) chain, respectively. Each glycopeptide contained one
      sequence, -Asn-Xaa-Thr-, which was shown to be N-glycosylated at Asn,
      corresponding to position 126 of the alpha 1 chains and 138 of the alpha 2 chain.
      1H NMR spectroscopic analysis of the oligosaccharide is a biantennary N
      acetyllactosamine type of N-linked oligosaccharide with a broad heterogeneity in
      the presence of the sugar residues at their nonreducing termini as indicated.
      [formula: see text] The location of the Asn-linked oligosaccharide units and Hyl
      linked disaccharide units and their orientation with respect to the surface of
      the triple helix were calculated using two models. We conclude that both units
      are important determinants in the assembly of the 7 S tetramer.

PMID- 1990012
TI  - Insertion of diphtheria toxin B-fragment into the plasma membrane at low pH.
      Characterization and topology of inserted regions.
AB  - When the enzymatically active A-fragment of diphtheria toxin is translocated to
      the cytosol, the B-fragment inserts into the membrane in such a way that a 25-kDa
      polypeptide becomes shielded from proteases added to the external medium. We have
      attempted to determine the boundaries of this polypeptide within the toxin B
      fragment as well as the topology of the B-fragment in the membrane. Chemical
      cleavage of the 25-kDa polypeptide with hydroxylamine and o-iodosobenzoic acid
      yielded fragments of sizes indicating that the 25-kDa polypeptide starts at
      residue approximately 300 and extends to the COOH-terminal end. Experiments where
      the toxin was labeled with [35S]cysteine at distinct positions of the B-fragment
      supported this conclusion. Treatment of cells with inserted B-fragment with L-1
      tosyl-amido-2-phenylethyl chloromethyl ketone-treated trypsin and with V8
      protease from Staphylococcus aureus yielded protected 27- and 30-kDa fragments in
      addition to 25 kDa, indicating that the region 240-264 is also at the outside.
      The topology of the inserted B-fragment is discussed.

PMID- 1990013
TI  - Antidiabetic AD4743 enhances adipocyte differentiation of 3T3 T mesenchymal stem
      cells.
AB  - AD4743 is an antidiabetic agent that, when added to fetal bovine serum (FBS), has
      been shown to have adipogenic activity for some proadipocyte cell lines once they
      reach confluence. In the current study, the effects of AD4743 on the growth and
      adipocytic differentiation of 3T3 T multipotential mesenchymal stem cells have
      been tested. 3T3 T cells, unlike other cells capable of undergoing adipocyte
      differentiation, are routinely induced to differentiate at low cell density. This
      is done using platelet-poor human plasma (HP), a potent inducer of growth arrest
      and differentiation. AD4743 (0-200 micrograms/ml) was tested in varied
      concentrations of HP or FBS, at varied cell densities, and at various times
      during growth and differentiation. AD4743 slowed the growth rate of 3T3 T cells
      and it induced their differentiation in a dose-dependent manner in medium
      containing 10% FBS once they reached confluence. The data suggest that the
      ability of AD4743 to inhibit growth may also be coupled with its ability to
      enhance differentiation. In addition, AD4743 (1-10 micrograms/ml) in the presence
      of 25% HP markedly increased the kinetics of adipocyte differentiation, at low
      (less than 5,000 cells/cm2) or high cell density. Greater than 50% cell
      differentiation could be achieved in 2 days in low density cultures; 80-95%
      differentiation could be achieved in just 4 days, compared to 8-12 days in a
      typical culture. The maximum amount of differentiation in HP was potentiated by
      AD4743 to a greater degree in poor lots of HP; however, the kinetics were
      increased in all lots. Adipocytic differentiation was measured both
      morphologically and by Northern blot analyses of differentiation-specific genes.
      AD4743 at 1-10 micrograms/ml appeared to be most effective, depending on the cell
      density and other conditions. The mechanism of action of AD4743 remains to be
      elucidated, but the enhancement of adipocyte differentiation does not appear to
      occur via an insulin-dependent pathway.

PMID- 1990015
TI  - Nature of enhanced mitochondrial oxidative metabolism by a calf blood extract.
AB  - The effect of calf blood extract (Solcoseryl, SS) on mitochondrial oxidative
      function in various states was studied polarographically in vitro. 1)
      Mitochondrial respiration in all 4 conventional study states (Estabrook, 1967)
      was enhanced by the addition of SS, including states 1 and 2 (endogenous
      substrates only). 2) The effect of SS on mitochondrial oxygen consumption was
      concentration dependent, while ADP/O ratio remained constant. The effect of added
      respiratory substrates varied with the particular substrate at optimally active
      concentrations. With suboptimal substrate levels, ADP/O ratios were concentration
      dependent, in contrast to the SS effect. Under oligomycin ATPase inhibition, SS
      was no longer active, in contrast to DNP, which remained active. 3) In states 3
      (added ADP) and 4 (ADP exhausted), oxygen consumption and oxidative
      phosphorylation were enhanced by SS in the presence or absence of citrate,
      glutamate, pyruvate, lactate, or ascorbate. However, in the presence of
      succinate, SS had no effect. 4) ADP/O ratio was decreased by SS in the presence
      of added substrate, suggesting that SS activation of H(+)-ATPase enhances ATP
      hydrolysis as well as oxidative phosphorylation and ATP synthesis. 5) The
      enhancing effect of SS on mitochondrial function is due to hydrophilic components
      of SS. The lipidic components obtained by Folch fraction of SS have no effect. It
      is concluded that the effects of SS respiratory substrates and uncouplers on
      mitochondrial function are essentially different. SS enhances both ATP synthesis
      and oxygen consumption by mitochondria.

PMID- 1990014
TI  - Modulation of milk protein synthesis through alteration of the cytoskeleton in
      mouse mammary epithelial cells cultured on a reconstituted basement membrane.
AB  - Recent studies indicate that the cytoskeleton may be involved in modulating
      tissue-specific gene expression in mammalian cells. We have studied the role of
      the cytoskeleton in regulating milk protein synthesis and secretion by primary
      mouse mammary epithelial cells cultured on a reconstituted basement membrane that
      promotes differentiation. After 8 days in culture, cells were treated with
      cytochalasin D (CD) (0.5-1 micrograms/ml) to alter actin filaments or acrylamide
      (Ac) (5 mM) to alter intermediate filaments (cytokeratins). CD inhibited
      synthesis of most proteins in a concentration-dependent manner, with beta-casein
      being the first affected. In contrast, Ac increased protein synthesis and
      secretion by 17-31% after a 12 hr treatment. Polyacrylamide gel electrophoresis
      of total secreted proteins indicates that synthetic rates of most proteins were
      increased equally by Ac treatment. This increase is apparently controlled at the
      level of translation, because control and Ac-treated cells contained the same
      amount of poly-A+ RNA, and neither CD nor Ac altered mRNA levels for beta-casein.
      There was also no indication that either CD or Ac can induce the expression of
      milk proteins in quiescent cells cultured on a plastic substratum. In conjunction
      with the biochemical studies, changes in cytoskeletal morphology caused by the
      drug treatments were analyzed by immunofluorescence microscopy. As has been
      observed in other cell types, low concentrations of CD caused cells to round up
      by disrupting actin filaments. Ac treatment slightly decreased the intensity of
      actin staining, but no changes in microfilament organization were observed. Ac
      treated cells showed slight disorganization of the cytokeratin filaments, with
      some peripheral interfibrillar bundling, but the cytokeratin network did not
      collapse and no retraction of cell extensions or breakdown of cell-cell contacts
      was observed. These results confirm previous reports that the actin cytoskeleton
      may play a role in regulating tissue-specific protein synthesis. How Ac
      stimulates protein synthesis is unknown, but it is unlikely that this effect is
      directly mediated through intermediate filaments.

PMID- 1990016
TI  - Evidence for extralysosomal hydrolysis of high-density lipoprotein cholesteryl
      esters in rat hepatoma cells (Fu5AH): a model for delivery of high-density
      lipoprotein cholesterol.
AB  - Rat hepatoma cells (Fu5AH) were studied as a model for the net delivery of apoE
      free high-density lipoprotein (HDL) cholesterol to a cell. Incubating cells with
      HDL results in 1) a decrease in both media-free cholesterol and cholesteryl ester
      concentration; 2) decreased cell sterol synthesis; and 3) increased cell
      cholesteryl ester synthesis. HDL cholesteryl ester uptake is increased when cells
      are incubated for 18 hr in cholesterol poor media. Coincubation of 3H-cholesteryl
      ester-labeled low-density lipoprotein (LDL) with 50 microM chloroquine or 25
      microM monensin results in a decrease in the cellular free
      cholesterol/cholesteryl ester (FC/CE) isotope ratio, indicating an inhibition in
      the conversion of cholesteryl ester to free cholesterol. In contrast, chloroquine
      and monensin do not alter the cellular FC/CE isotope ratio for 3H-CE HDL. This
      evidence indicates that acidic lysosomal cholesteryl ester hydrolase does not
      account for the hydrolysis of HDL-CE. Free cholesterol generated from 3H
      cholesteryl ester of both LDL and HDL is reesterified intracellularly. At higher
      HDL concentrations (above 50 micrograms/ml) HDL cholesteryl ester hydrolysis is
      sensitive to chloroquine. We propose that an extralysosomal pathway is operating
      in the metabolism of HDL cholesterol and that at higher HDL concentrations a
      lysosomal pathway may be functioning in addition to an extralysosomal pathway.

PMID- 1990017
TI  - Activation of cell membrane potassium conductance by mercury in cultured renal
      epithelioid (MDCK) cells.
AB  - To elucidate mechanisms of mercury toxicity, the cell membrane potential has been
      determined continuously in cultured kidney (MDCK)-cells during reversible
      application of mercury ions to extracellular perfusate. Exposure of the cells to
      1 microM mercury ions is followed by rapid, sustained, and slowly reversible
      hyperpolarization of the cell membrane, increase of cell membrane potassium
      selectivity, and decrease of cell membrane resistance. Thus, mercury ions enhance
      the potassium conductance of the cell membrane. Half maximal hyperpolarizing
      effect is elicited by approximately 0.2 microM. Higher concentrations of mercury
      ions (greater than 10 microM) eventually depolarize the cell membrane. At
      extracellular calcium activity reduced to less than 0.1 microM, 1 microM mercury
      ions still leads to a sustained hyperpolarization and increase of potassium
      selectivity of the cell membrane. As evident from fluorescence measurements, 10
      microM, but not 1 microM mercury ions leads to a rapid increase of intracellular
      calcium activity. Pretreatment of the cells with either pertussis toxin or
      cholera toxin does not blunt the hyperpolarizing effect of mercury ions. In
      conclusion, mercury ions activate the potassium conductance by a mechanism
      independent of increase of intracellular calcium activity and of cholera toxin-
      or pertussis toxin-sensitive G-proteins. This activation of potassium conductance
      may account for early effects of mercury intoxication, such as kaliuresis.

PMID- 1990018
TI  - Effects of hypertonic and sodium-free medium on transport of a membrane
      glycoprotein along the secretory pathway in cultured mammalian cells.
AB  - Incubation of cultured cells in hypertonic medium and sodium-free medium have
      been shown to block transport at two different stages along the endocytic
      pathway. To determine the effects of these treatments on the exocytic pathway, we
      studied the transport of the membrane glycoprotein of vesicular stomatitis virus
      (VSV-G) in cells infected with tsO45 mutant virus. This mutant synthesizes a VSV
      G that accumulates in the endoplasmic reticulum (ER) when cells are incubated at
      39.5 degrees C. In addition, VSV-G accumulates in the post-ER pre-Golgi
      compartment when cells are incubated at 15 degrees C and in the trans-Golgi
      network (TGN) when cells are incubated at 18 degrees C. Upon transfer of cells to
      32 degrees C in control medium, VSV-G exits each of these compartments and is
      transported to the cell surface. Incubation in sodium-free medium at 32 degrees C
      did not block transport from any of these three compartments. In contrast,
      incubation in hypertonic medium blocked export from the ER, transport from the
      pre-Golgi compartment to the Golgi complex, and transport from the TGN to the
      cell surface. Our results, in combination with previous studies, suggest that
      hypertonic medium blocks at least five distinct transport steps; the three
      exocytic steps described here, endocytosis from the cell surface, and transport
      of cell surface proteins into the Golgi complex. This raises the possibility that
      vesicular transport in different parts of the cell shares common elements that
      are inhibited by this treatment.

PMID- 1990019
TI  - Homocysteine export from cells cultured in the presence of physiological or
      superfluous levels of methionine: methionine loading of non-transformed,
      transformed, proliferating, and quiescent cells in culture.
AB  - Determination of the transient increase in plasma homocysteine following
      administration of excess methionine is an established procedure for the diagnosis
      of defects in homocysteine metabolism in patients. This so-called methionine
      loading test has been used for 25 years, but the knowledge of the response of
      various cell types to excess methionine is limited. In the present paper we
      investigated homocysteine export from various cell types cultured in the presence
      of increasing concentrations (15-1,000 microM) of methionine. For comparison of
      homocysteine export, the export rates per million cells were plotted versus cell
      density for proliferating cells, and versus time for quiescent cells. The
      homocysteine export from growing cells was greatest during early to mid
      exponential growth phase, and then decreased as a function of cell density. The
      export rate was higher from phytohemagglutinin-stimulated than non-stimulated
      lymphocytes, and higher from proliferating than from quiescent fibroblasts. The
      hepatocytes showed highest export rate among the cell types investigated. The
      enhancement of homocysteine export by excess methionine ranged from no
      stimulation to marked enhancement, depending on cell type investigated, and three
      different response patterns could be distinguished: 1) quiescent fibroblasts and
      growing murine lymphoma cell showed no significant increase in homocysteine
      export following methionine loading; export from human lymphocytes was only
      slightly enhanced in the presence of excess methionine; 2) the homocysteine
      export from proliferating hepatoma cells and benign and transformed fibroblasts
      was stimulated three to eightfold by increasing the methionine concentration in
      the medium from 15 to 1,000 microM; and 3) the response to methionine loading was
      particularly increased (about 15-fold) in non-transformed primary hepatocytes in
      stationary culture. The results outline a potentially useful procedure for the
      comparison of homocysteine export during cell growth in the presence of various
      concentrations of methionine. The results are discussed in relation to the
      special feature of homocysteine metabolism in various cell types and tissues
      including liver, and to the possible source of plasma homocysteine following
      methionine loading in vivo.

PMID- 1990020
TI  - Epidermal growth factor treatment of A431 cells alters the binding capacity and
      electrophoretic mobility of the cytoskeletally associated epidermal growth factor
      receptor.
AB  - The epidermal growth factor (EGF) receptor interacts with structural elements of
      A431 cells and remains associated with the cytoskeleton following extraction with
      nonionic detergents. Extraction of cells with 0.15% Triton X-100 resulted in
      detection of only approximately 40% of the EGF binding sites on the cytoskeleton.
      If the cells were exposed to EGF prior to extraction, approximately twofold
      higher levels of low-affinity EGF binding sites were detected. The difference in
      number of EGF binding sites was not a consequence of differences in numbers of
      EGF receptors associated with the cytoskeleton; equal amounts of 35S-labeled
      receptor were immunoprecipitated from the cytoskeletons of both control and EGF
      treated cells. The effect of EGF pretreatment on binding activity was coincident
      with a change in the mobility of the receptor from a doublet of Mr approximately
      160-180 kDa to a single sharp band at 180 kDa. The alteration in receptor
      mobility was not a simple consequence of receptor phosphorylation in that the
      alteration was not reversed by alkaline phosphatase treatment, nor was the shift
      produced by treatment of the cells with phorbol ester. The two EGF receptor
      species demonstrated differential susceptibility to V8 proteinase digestion. The
      EGF-induced 180 kDa species was preferentially digested by the proteinase
      relative to the 160 kDa species, indicating that EGF binding results in a
      conformational change in the receptor. The EGF-mediated preservation of binding
      activity and altered conformation may be related to receptor oligomerization.

PMID- 1990021
TI  - Macrovascular and microvascular endothelium during long-term hypoxia: alterations
      in cell growth, monolayer permeability, and cell surface coagulant properties.
AB  - In bovine aortic or capillary endothelial cells (ECs) incubated under hypoxic
      conditions, cell growth was slowed in a dose-dependent manner at lower oxygen
      concentrations, as progression into S phase from G1 was inhibited, concomitant
      with decreased thymidine kinase activity. Monolayers grown to confluence in
      ambient air, wounded, and then transferred to hypoxia showed decreased ability to
      repair the wound, as a result of both decreased motility and cell division.
      Hypoxic ECs demonstrated a approximately 3-fold increase in the total number of
      high-affinity fibroblast growth factor receptors, and levels of endogenous FGF
      were suppressed. Consistent with the presence of functional FGF receptors,
      addition of basic FGF overcame, at least in part, hypoxia-mediated suppression of
      EC growth, and enhanced wound repair in hypoxia, stimulating both motility and
      cell division. Despite slower growth in hypoxia, ECs could achieve confluence,
      and the monolayers consisted of larger cells with altered assembly of the actin
      based cytoskeleton and small gaps between contiguous cells. The permeability of
      these hypoxic EC monolayers to macromolecules and lower molecular weight solutes
      was increased. Cell surface coagulant properties were also perturbed: the
      anticoagulant cofactor thrombomodulin was suppressed, and a novel Factor X
      activator appeared on the EC surface. These data indicate that micro- and
      macrovascular ECs can grow and be maintained at low oxygen tensions, but hypoxic
      endothelium exhibits a range of altered functional properties which can
      potentially contribute to the pathogenesis of vascular lesions.

PMID- 1990022
TI  - Prostaglandins do not mediate the actions of cholera toxin on pancreatic acini or
      gastric chief cells from the guinea pig.
AB  - Recent reports suggest that prostaglandins, rather than cAMP, play a major role
      in mediating cholera toxin-induced water and electrolyte secretion from rabbit
      intestinal loops. We examined the role of prostaglandins in mediating toxin
      induced pancreatic and gastric exocrine secretion. In these tissues,
      indomethacin, a potent inhibitor of prostaglandin synthesis, did not alter the
      stimulatory effects of cholera toxin on increases in cellular cAMP or enzyme
      secretion. Moreover, the addition of cholera toxin did not alter prostaglandin E2
      release from either tissue. In contrast to their effects in rabbit intestinal
      loops, prostaglandins do not regulate cholera toxin-induced enzyme secretion from
      the guinea pig pancreas or stomach.

PMID- 1990023
TI  - Role of intracellular-free calcium in the cornified envelope formation of
      keratinocytes: differences in the mode of action of extracellular calcium and
      1,25 dihydroxyvitamin D3.
AB  - Extracellular calcium (Cao) and the steroid hormone 1,25(OH)2D, induce the
      differentiation of human epidermal cells in culture. Recent studies suggest that
      increases in intracellular free calcium (Cai) levels may be an initial signal
      that triggers keratinocyte differentiation. In the present study, we evaluated
      cornified envelope formation, the terminal event during keratinocyte
      differentiation, and correlated it with changes in the Cai levels during
      differentiation of keratinocytes in culture induced by Cao or 1,25(OH)2D.
      Keratinocytes were grown in different Cao concentrations (0.1 or 1.2 mM) or in
      the presence of 1,25(OH)2D (10(-11) to 10(-7) M), and the Cai levels were
      measured using the fluorescent probe Indo-1. Our results suggest that the
      induction of cornified envelope formation is associated with an increase in Cai
      level during calcium-induced differentiation. Cao and the calcium ionophore
      ionomycin acutely increased Cai and cornified envelope formation. In contrast,
      the effect of 1,25(OH)2D on increasing Cai levels and stimulating cornified
      envelope formation was long-term, requiring days of treatment with 1,25(OH)2D.
      Our data are consistent with other recent studies and support the hypothesis that
      Cao regulates keratinocyte differentiation primarily by acutely increasing their
      Cai levels. The role of calcium in the mechanism of action of 1,25(OH)2D on
      keratinocyte differentiation is less clear. The increase in Cai of keratinocytes
      during 1,25(OH)2D induced differentiation may be essential for or subsequent to
      its prodifferentiation effects.

PMID- 1990024
TI  - Abstracts of papers. 69th general session, International Association for Dental
      Research; 20th annual session, American Association for Dental Research; 12th
      annual session, Mexican Division of the IADR, April 17-21, 1991, Acapulco,
      Mexico.

PMID- 1990025
TI  - Planning, implementation, and evaluation of AIDS education programs for dentists.
AB  - Because many dentists were trained before HIV disease was recognized and its
      implications for dentistry understood, there is a need for effective continuing
      education programs about the disease for health professionals. Unfortunately,
      much of the continuing professional education about AIDS in the last few years
      has been poorly evaluated and the value of continuing education itself has
      increasingly been called into question. In order to clarify how continuing
      educational efforts can be designed and evaluated, we report on our continuing
      educational projects and research which culminated in research on a nationwide
      educational intervention about AIDS for dentists. We outline and evaluate the
      steps taken in designing both the intervention and the research. The strengths
      and weaknesses of the design are discussed and suggestions made about how the
      design could be improved.

PMID- 1990027
TI  - Patterns in comprehensive care clinical educational schools.

PMID- 1990026
TI  - Effectiveness of student ratings feedback and consultation for improving
      instruction in dental school.
AB  - The effects of student ratings feedback and consultation on instructional
      improvement over a four-year time interval were examined. Of the 40 course
      directors who led the same course over a four-year period, nine sought
      consultation services after receiving results from their initial student course
      evaluation. A sample of nine course directors who received student ratings
      feedback but did not seek consultation were matched to this consultation group,
      and student ratings comparisons were made over the subsequent three-year period.
      The consultation group received significantly higher ratings than the ratings
      only group for six of the nine course rating items. The magnitude of these effect
      sizes were substantial. When viewed in light of previously reported controlled
      studies on feedback, the results suggest that consultation is an important
      adjunct to ratings feedback for improving subsequent instruction in dental
      education. In response to an attitudinal survey, course directors indicated that
      students were qualified to rate aspects of instruction and that ratings provided
      useful feedback for making course improvements. Recommendations for using student
      ratings feedback are provided.

PMID- 1990028
TI  - Assessing information resource needs in a college of dentistry.

PMID- 1990029
TI  - The option "none of these" improves multiple-choice test items.

PMID- 1990030
TI  - A ten year follow-up of attitudes toward evaluation in behavioral aspects of
      clinical practice.

PMID- 1990031
TI  - A clinical implant program in the predoctoral curriculum.

PMID- 1990032
TI  - A marketing plan for ET nursing.

PMID- 1990033
TI  - Social support, coping strategies, and long-term adaptation to ostomy among self
      help group members.

PMID- 1990034
TI  - The product evaluation process.
AB  - As new ET nurses and other nursing specialists assume positions on PEC, they will
      require knowledge of the process and problems that might occur. This article,
      describing a method of product selection and managing one's business relationship
      with sales representatives, is designed to help new ET nurses develop and
      maintain an issues oriented, professional image throughout the selection process.

PMID- 1990035
TI  - Urinary collection devices in geriatric incontinence.

PMID- 1990036
TI  - Perceptions of sexuality after ostomy surgery.

PMID- 1990038
TI  - Brown spider bites.

PMID- 1990037
TI  - Approach to pneumomediastinum.

PMID- 1990039
TI  - Living will amendment to protocol.

PMID- 1990040
TI  - Good physician-patient relationship = improved patient outcome?

PMID- 1990042
TI  - The values history. The evaluation of the patient's values and advance
      directives.
AB  - Autonomous decision making by patients can be enhanced by a variety of advance
      directives. These directives, the living will and the durable power of attorney,
      have an ethical and legal basis on which the patient can prospectively make
      decisions about life-sustaining therapies. The strength of these directives can
      be enhanced by the use of the Values History, serving as an adjunct to them. The
      Values History can also be used as a clinical tool to elicit the values of the
      patient as they pertain to chronic as well as critical medical care.
      Documentation of the patient's values will give the health care team a fuller
      understanding of the patient's preferences and directions.

PMID- 1990041
TI  - Treatment of beta-hemolytic streptococcal pharyngitis with cefaclor or
      penicillin. Efficacy and interaction with beta-lactamase-producing organisms in
      the pharynx.
AB  - The recommended treatment for group A beta-hemolytic streptococcal pharyngitis
      has continued to be penicillin given in parenteral or oral form. Treatment
      failures, as determined by the continued presence of the streptococcal organism
      in the pharynx, however, do occur in 6% to 25% of patients treated with
      penicillin. Furthermore, beta-lactamase produced by other bacteria in the pharynx
      could potentially inactivate the penicillin, resulting in increased treatment
      failures or infection relapses. A study was undertaken to compare the efficacy of
      cefaclor, which is relatively resistant to inactivation by beta-lactamase, with
      penicillin for eradicating the group A beta-hemolytic streptococcal organism from
      the throats of 93 patients with pharyngitis. Additionally, extensive cultures for
      potential beta-lactamase-producing organisms were conducted on 37 patients; 27%
      of these had one or more pharyngeal organisms that were producing beta-lactamase.
      No statistically significant difference was found between the clinical responses
      or the bacteriological cure rates of those treated with cefaclor and those
      treated with penicillin when stratified by the presence or absence of beta
      lactamase-producing organisms. The prevalence of beta-lactamase-producing
      organisms in the pharynx, however, was increased after treatment with penicillin,
      whereas no change was noted following treatment with cefaclor.

PMID- 1990043
TI  - AIDS in California family medicine. Changing experiences, knowledge, and
      geographic distribution.
AB  - Information regarding practice patterns specific to acquired immunodeficiency
      syndrome (AIDS) was obtained in 1988 from 1774 family physicians in California
      using a mail survey. Data were analyzed across the following county groupings:
      Los Angeles County, other counties in standard metropolitan statistical areas,
      and counties outside standard metropolitan statistical areas. Comparisons were
      made with the data from a telephone survey conducted in 1986. Differences over
      time were analyzed. By 1988, the percentage of physicians treating or referring
      patients for possible AIDS had more than doubled in counties outside standard
      metropolitan statistical areas. The percentage of physicians reporting one or
      more diagnosed cases of AIDS had tripled, a finding that suggests the importance
      of AIDS in family medicine is increasing at a rapid rate. In addition, survey
      results indicate that a majority of those surveyed still lack the AIDS-related
      knowledge and competency necessary to effectively deal with AIDS.

PMID- 1990044
TI  - Changes in women's mental and physical health from pregnancy through six months
      postpartum.
AB  - A longitudinal study was conducted to investigate changes in women's mental and
      physical health around the time of childbirth, and to determine whether health
      was related to length of maternity leave. Thirty-seven married, employed first
      time mothers completed questionnaires during pregnancy, and again at 6 weeks, 3
      months, and 6 months postpartum. Results showed that, from pregnancy to the 6th
      postpartum month, the number of days that mothers were ill because of infections
      steadily increased. In addition, depressive symptoms for new mothers rose from
      pregnancy to the 6th week postpartum, and declined thereafter. For women who did
      not return to work during the period of the study, a significant decline in
      depressive symptoms was observed from the prenatal period through the 6th
      postpartum month. These findings demonstrate significant changes in mental and
      physical health for this group of first-time mothers.

PMID- 1990045
TI  - Gatekeeper effects on patterns of physician use.
AB  - The impact of primary care gatekeeping on selected patterns of physician use was
      examined among Medicaid beneficiaries in two demonstration programs. The evidence
      indicates that beneficiaries enrolled with gatekeepers were significantly less
      likely to see specialists when compared with unenrolled beneficiaries in
      comparison groups. Primary care visits increased to offset these reductions only
      when gatekeepers were paid on a fee-for-service basis. Increased overall reliance
      on primary care physicians as opposed to specialists was also observed in the
      gatekeeper programs. Findings also indicate that enrolled beneficiaries received
      care from fewer sources than they had prior to enrollment. Although these changes
      in patterns of use have the potential to assure access to a more stable and
      structured system of care, the clinical and long-term economic consequences of
      such changes remain unknown.

PMID- 1990046
TI  - The relationship of physician medical interview style to patient satisfaction.
AB  - The results of previous studies on the relationship between patient satisfaction
      and specific interviewing behaviors have been difficult to generalize because
      most studies have examined small samples of patients at one clinical location,
      and have used initial or acute care visits where the patient and physician did
      not have an established relationship. The present collaborative study of medical
      interviewing provided an opportunity to collect interviews from 550 return visits
      to 127 different physicians at 11 sites across the country. Tape recordings were
      analyzed using the Roter Interaction Analysis System, and postvisit satisfaction
      questionnaires were administered to patients. A number of significant
      relationships were found between communication during the visit and the various
      dimensions of patient satisfaction. Physician question asking about biomedical
      topics (both open- and closed-ended questions) was negatively related to patient
      satisfaction; however, physician question asking about psychosocial topics was
      positively related. Physician counseling for psychosocial issues was also
      positively related to patient satisfaction. Similarly, patient talk about
      biomedical topics was negatively related to satisfaction, while patient talk
      regarding psychosocial topics was positively related. Furthermore, patients were
      less satisfied when physicians dominated the interview by talking more or when
      the emotional tone was characterized by physician dominance. The findings suggest
      that patients are most satisfied by interviews that encourage them to talk about
      psychosocial issues in an atmosphere that is characterized by the absence of
      physician domination.

PMID- 1990047
TI  - Chronic pain in primary care. Identification and management of psychosocial
      factors.
AB  - Chronic pain is a problem of great public health importance that is frequently
      seen in the primary care setting. Pain chronicity shows a strong association with
      psychosocial factors. Assessment of these factors should be composed of two
      parts: (1) psychological factors and (2) psychiatric illness. Psychological
      factors include all those pain-associated alterations in the patient's
      environment that reinforce illness behavior. Psychiatric illness includes those
      syndromes that retard recovery from illness or injury, such as depression,
      anxiety, substance abuse, and dementia. Psychiatric and psychological
      interventions can be successfully introduced in the context of a comprehensive
      rehabilitation effort. Usually these interventions can be accomplished by the
      family physician in concert with a consultant psychiatrist or psychologist. In
      severely disabled or resistant patients, referral to a multidisciplinary pain
      clinic will be necessary.

PMID- 1990048
TI  - Religion and family medicine: a survey of physicians and patients.

PMID- 1990049
TI  - Prenatal detection of HIV seropositivity in an urban practice.

PMID- 1990050
TI  - Fate of haploid parthenogenetic cells in mouse chimeras during development.
AB  - The developmental capability of haploid parthenogenetic cells was investigated by
      studies on haploid parthenogenetic in equilibrium fertilized mouse chimeras. Two
      chimeras were born. One female chimera was smaller at birth and grew slower than
      its littermates. The distribution of haploid-derived cells in the chimeras was
      analyzed 11 months after their birth. Cells derived from haploid embryos were
      found only in the brain, eyes, pigment cells in hair follicles, and spleen, in
      which they constituted 30%, 20%, 10%, and less than 5%, respectively, of the
      cells. The correlation between the parthenogenetic contribution to the brain and
      growth retardation is discussed. All of the cells examined in these chimeric
      organs (brain and eyes) contained a diploid amount of DNA, suggesting that
      diploidization of the haploid parthenogenetic cells occurred during development.
      Possibly, the haploid state is not sufficient for cell growth, even in chimeras
      with fertilized embryos.

PMID- 1990051
TI  - Selective growth and serial passage of mouse melanocytes from neonatal epidermis
      in a medium supplemented with bovine pituitary extract.
AB  - Suspensions of disaggregated epidermal cells from skins of newborn C57BL/10JHir
      mice were plated in a growth medium that consisted of Ham's F-10 plus bovine
      pituitary extract (BPE), insulin, and transferrin. Fetal bovine serum (FBS) was
      added to the culture medium at a concentration of 4% at the time of plating. On
      the second day of culture, a small number of melanocytes was randomly distributed
      among large sheets of keratinocytes. From the third day onward, FBS was excluded
      from the culture medium to prevent the proliferation of keratinocytes and
      fibroblasts. The melanocytes began to grow preferentially, and after 12 days pure
      and enriched populations of melanocytes could be harvested. In the absence of the
      proliferation of keratinocytes and fibroblasts, melanocytes could be serially
      passaged in the growth medium supplemented with a conditioned medium (CM)
      prepared from keratinocyte-enriched cultures, namely, those at the early stages
      of the primary culture. FBS was added at a concentration of 1% for the first day.
      These results suggest that both BPE and keratinocyte CM contain growth factors
      required for proliferation of melanocytes.

PMID- 1990052
TI  - Expression of the cell adhesion molecules, L-CAM and N-CAM during avian scale
      development.
AB  - To examine the involvement of cell adhesion molecules in the inductive epithelial
      mesenchymal interactions during avian scale development, a study of the
      spatiotemporal distribution of L-CAM and N-CAM was undertaken. During scutate
      scale development, L-CAM and N-CAM are expressed together in cells of the
      transient embryonic layers destined to be lost at hatching. The ongoing linkage
      of the cells of these layers by both CAMs sets them apart, early in development,
      as unique cell populations. L-CAM and N-CAM were also expressed simultaneously at
      the basal surface of the early germinative cells where signal transduction is
      presumed to occur. In spite of the differences in cell shape, adhesion, density
      and proliferative state between populations of epidermal placode and interplacode
      cells, the expression of L-CAM and N-CAM appeared to be uniform and
      nondiscriminating for these discrete cell lineages. The same pattern of L-CAM and
      N-CAM expression was observed during morphogenesis of reticulate scales that
      develop without placode formation. While L-CAM and N-CAM are present during the
      early stages of scale development and most likely function in cell adhesion, the
      data do not support a role for these adhesion molecules in the formation of the
      morphogenetically critical placode and interplacode cell populations. In both
      scale types, L-CAM became predominantly epithelial, and N-CAM became
      predominantly dermal as histogenesis occurred. Initially, N-CAM was concentrated
      near the basal lamina where it may be involved in the reciprocal epidermal-dermal
      interactions required for morphogenesis. However, as development of the scales
      progressed, N-CAM disappeared from the tissues. L-CAM expression continued in the
      epidermis and was intense on all suprabasal cells undergoing differentiation into
      either an alpha-stratum or beta-stratum. However, L-CAM was more prevalent on the
      basal cells of alpha-keratinizing regions than on the basal cells of beta
      keratinizing regions.

PMID- 1990053
TI  - Fibroblast growth factor and culture in monolayer rescue mesoderm cells destined
      to die in the developing avian wing.
AB  - In an effort to elucidate control mechanisms for developmentally programmed cell
      death, conditions were sought that rescue the cells destined to die. Three areas
      of mesodermal cell death in the chick wing were examined: the posterior necrotic
      zone (PNZ), the opaque patch (OP), and apical mesoderm. The PNZ and OP are areas
      of normally programmed cell death, whereas the apical mesoderm undergoes cell
      death only after the overlying apical ectodermal ridge is excised. Cell death in
      vitro was quantitated using the chromium-release assay. While these tissues
      undergo apparently normal cell death in organ culture, in monolayer culture
      almost all are rescued. In addition, the cells are rescued by the addition of
      fibroblast growth factor to organ cultures. Since fibroblast growth factor is
      present in decreasing amounts in the limb at this stage of development, normal
      cell death may occur upon withdrawal of growth factor.

PMID- 1990054
TI  - Production of identical twin and triplet mice by nuclear transplantation.
AB  - Transplantation of a single nucleus from two- or four-cell embryos into one of
      the enucleated blastomeres of a two-cell embryo resulted in successful production
      of identical triplet and twin mice. The proportion of reconstituted embryos that
      developed in blastocysts was 71% (84/118) when four-cell embryos were used as
      donors of nuclei; 10 sets of quadruplet and nine sets each of triplet and twin
      blastocysts were obtained by this technique. After transfer to recipients, 30%
      (18/61) developed to term, and one set of identical triplet and four sets of
      identical twin mice were obtained. When two-cell embryos were used as donors of
      nuclei, 79 (95%) sets of twin embryos developed to blastocysts. Of 38 twin
      blastocysts transferred to recipients, 21 sets (55%) developed to term as
      identical twin mice. These results demonstrate that the enucleated two-cell
      embryo develops in vitro after transfer of a nucleus from a two- or four-cell
      embryo and the resultant blastocyst has high potential for development to term
      after transfer to a recipient.

PMID- 1990055
TI  - Ontogeny of the olfacto-retinalis projection in coho salmon (Oncorhynchus
      kisutch).
AB  - Filling of nucleus olfacto-retinalis neurons by cobaltous lysine injections into
      one eye of coho salmon of different ages revealed that the terminal nerve
      projection to the retina is established when the fish leave their freshwater
      environment. At this time salmons go through a metamorphosis termed
      "smoltification." FMRF-amide-like immunoreactive neurons in the nucleus olfacto
      retinalis already exist in pre-smolts before the retino-petal projection is
      established. Thus, for the first time in any vertebrate, a projection of the
      terminal nerve is shown to develop during an advanced ontogenetic state.

PMID- 1990056
TI  - Potassium dependence for sperm-egg fusion in mice.
AB  - In this study, we examined the potassium requirements for sperm-egg fusion in
      mouse. Zona-free mouse eggs prepared by the method described by Boldt and Wolf
      were inseminated with capacitated sperm in culture media containing 0-6 mM
      extracellular K+, and scored for penetration. Penetration of zona-free eggs was
      dependent on extracellular K+, with no penetration observed under K(+)-free
      conditions. Media transfer experiments indicated that the lack of penetration
      observed was due to effects on fusion, and not on postpenetration events such as
      sperm head decondensation. To analyze whether the K+ effect was attributable to
      an effect on the sperm (i.e., occurrence of acrosome reactions), sperm were
      treated with the Ca2+ ionophore A23187 before insemination. Less than 5% of zona
      free eggs were penetrated with ionophore-treated sperm under K(+)-free
      conditions, suggesting that K+ is required for fusion per se. Addition of
      ionophore to insemination cultures similarly did not overcome the block to fusion
      observed under K(+)-free conditions. The potassium channel blockers 4
      aminopyridine (0.1-5 mM) and tetraethyl ammonium chloride (5-50 mM) had no
      inhibitory effect on fusion. These data indicate that extracellular K+ is
      required for sperm-egg fusion and that this requirement may not involve membrane
      K+ channels.

PMID- 1990057
TI  - Tomato aspermy virus has an evolutionary relationship with other tripartite RNA
      plant viruses.
AB  - The entire RNA 3 (2214 nucleotides) of a chrysanthemum isolate of tomato aspermy
      virus (C-TAV) has been cloned and its sequence determined. C-TAV possesses two
      open reading frames which encode a 3a protein (277 amino acids) and a coat
      protein (229 amino acids). Computer-assisted comparisons were made between C-TAV
      RNA 3 and its predicted protein sequences and those of two other tripartite RNA
      viruses, cucumber mosaic virus (CMV) and brome mosaic virus (BMV). Results from
      this study suggest that a close evolutionary relationship exists between C-TAV, Q
      CMV and BMV. Divergence of nucleotide and amino acid sequences between these
      viruses is not reflected at the level of the predicted secondary structure of the
      encoded proteins, where conservation is strong.

PMID- 1990058
TI  - Antigenic characterization of the nucleoprotein and matrix protein of influenza C
      virus with monoclonal antibodies.
AB  - Monoclonal antibodies against the nucleoprotein (NP) and matrix (M) protein of
      influenza C virus were prepared and characterized. At least two non-overlapping
      or partially overlapping antigenic sites were delineated on each of the proteins
      by competitive binding assays. Western blot analysis showed that two antigenic
      sites on the M protein were highly resistant to conformational changes whereas
      two sites on NP were sensitive. No antigenic variation was seen in either the NP
      or the M protein when the reactivity of monoclonal antibodies with 23 different
      influenza C strains isolated over a 41 year period was studied by
      radioimmunoprecipitation and enzyme-linked immunosorbent assay.
      Immunofluorescence analysis with the monoclonal antibodies revealed that both the
      NP and M proteins migrated to the cell nucleus during the replication cycle of
      influenza C virus.

PMID- 1990059
TI  - Influenza virus enhancement of membrane leakiness induced by staphylococcal alpha
      toxin, diphtheria toxin and streptolysin S.
AB  - Release of alpha-amino[14C]isobutyric acid from ferret Mpf cells was promoted by
      staphylococcal alpha toxin, diphtheria toxin and streptolysin S. This release was
      enhanced to a significant extent if the cells had been previously infected with
      influenza virus strain A/Puerto Rico/8/34 (PR8, H1N1), although infection with
      virus alone did not increase the release of radiolabel as compared with that from
      untreated cells; inactivated virus had a similar enhancing action. The mechanism
      of enhancement is unclear but it occurs between 0.5 and 2h post-inoculation and
      viral membrane/endosome membrane fusion is essential. Endotoxin had no effect on
      membrane permeability, either alone or with PR8. The relevance of these in vitro
      observations to the previously observed enhancement of toxin lethality by
      influenza virus in vivo is discussed.

PMID- 1990060
TI  - Comparison of the virulence of wild-type thymidine kinase (tk)-deficient and tk+
      phenotypes of vaccinia virus recombinants after intranasal inoculation of mice.
AB  - A recombinant vaccinia virus vector was constructed which expressed the major
      surface glycoprotein G of human respiratory syncytial virus (RSV) and the
      thymidine kinase (tk) gene of vaccinia virus. The virulence of this tk+
      recombinant virus was compared with that of a tk- recombinant and the wild-type
      (wt) virus after intranasal inoculation of mice. Respiratory infection with wt
      virus resulted in a lethal infection with widespread dissemination of virus. In
      contrast, infection with the tk- recombinant was not lethal and the virus had a
      reduced ability to disseminate to extrapulmonary tissue compared with wt virus.
      Insertion of the tk gene restored the virulence of the recombinant virus to the
      level of that of the wt virus. Despite a dramatic reduction in virulence of the
      tk- recombinant, virus could occasionally be recovered from the brains of mice.
      The expression of the attachment glycoprotein of RSV appeared to enhance the
      ability of the tk- recombinant virus to replicate in the lungs when compared with
      recombinants expressing fusion or nucleoprotein genes. The results confirm that
      inactivation of the tk gene results in a dramatic reduction of virulence for mice
      but suggest that there is still a potential danger of infection of the brain
      following intranasal administration of virus.

PMID- 1990061
TI  - Nucleotide sequence of the 3'-terminal half of beet yellows closterovirus RNA
      genome: unique arrangement of eight virus genes.
AB  - The sequence of 6746 nucleotides representing the 3'-proximal half of the beet
      yellows closterovirus (BYV) genome was determined. In the direction 5' to 3', the
      sequence was composed of eight open reading frames (ORFs) potentially encoding
      proteins of 6.4K (ORF2), 65K (ORF3), 64K (ORF4), 24K (ORF5), 22K (ORF6), 20K
      (ORF7) and 21K (ORF8). An incomplete ORF, ORF1, encoded the C-terminal part of a
      putative RNA-dependent RNA polymerase, most closely related to polymerases of
      tricornaviruses; the putative product of ORF3, 65K, was found to be a homologue
      of the hsp70 family of cell heat-shock proteins. ORF2 potentially encoded a small
      hydrophobic 6.4K protein, apparently homologous to small hydrophobic proteins of
      potex- and carlaviruses. ORF6 encoded the viral coat protein, as indicated by its
      deduced Mr and amino acid composition. The products of ORFs 4, 5, 7 and 8 showed
      no significant similarities with protein sequences in the database and there are
      therefore no justifiable speculations concerning their possible functions. BYV
      RNA contains a 3'-terminal non-coding region of 181 nucleotides, with two stem
      loop structures potentially folded within the 86 nucleotide sequence at the
      extreme 3' end. Analysis of the primary and secondary structure of this region
      together with the absence of aminoacylation and adenylylation in vitro showed
      that the BYV genome is devoid of a tRNA-like structure at its 3' end.

PMID- 1990062
TI  - Direct isolation in eggs of influenza A (H1N1) and B viruses with haemagglutinins
      of different antigenic and amino acid composition.
AB  - Influenza A (H1N1) and influenza B viruses from clinical samples were isolated in
      the amniotic cavity of embryonated hens' eggs by classical techniques and
      propagated in the allantoic cavity. Virus progeny from different eggs which had
      been inoculated with virus material from the same clinical sample possessed
      antigenically distinguishable haemagglutinins (HAs). Virus progeny of some eggs
      possessed HAs which were serologically identical to those of virus isolated in
      parallel in mammalian (MDCK) cells. These egg-grown viruses possessing HAs with
      the antigenic phenotype of mammalian cell-grown viruses appeared to be
      antigenically related to epidemic influenza virus because post-infection human
      sera reacted to high titre with the virus HA. Specific nucleotide changes were
      detected in the HAs of the viruses isolated directly in eggs at positions 163 and
      189 for influenza A (H1N1) viruses or positions 141 and 196 to 198 for influenza
      B viruses. Egg-isolated viruses which possessed the antigenic phenotype of
      mammalian cell-grown viruses retained glycosylation sites at positions 163 and
      196. The viruses isolated directly in embryonated hens' eggs which possessed the
      HA antigenic phenotype and glycosylation sites of MDCK cell-grown virus can,
      unlike the latter viruses themselves, be used as candidate influenza vaccine
      viruses.

PMID- 1990063
TI  - The specific inhibition of influenza A virus maturation by amantadine: an
      electron microscopic examination.
AB  - Amantadine specifically inhibits the release of virus particles from cells
      infected with the Rostock (H7N1) strain of influenza A virus, apparently as a
      consequence of a membrane protein M2-mediated conversion of haemagglutinin (HA)
      to its low pH conformation. Electron microscopic observations, together with
      immunogold labelling, showed that amantadine action does not alter the
      distribution of HA on the cell surface nor does it prevent the formation of
      budding virus particles. It was not possible, however, to discern whether low pH
      HA inhibited the final stage in virus maturation, i.e. pinching off, or simply
      prevented release of fully formed particles.

PMID- 1990064
TI  - VPg-mediated aggregation of potyviral RNA.
AB  - RNA prepared from the potyvirus tobacco vein mottling virus contained aggregates
      of the 9.5 kb genomic RNA with electrophoretic mobilities corresponding to 20 and
      41 kb species. Similar aggregates were present in preparations of the RNAs of two
      other potyviruses. Aggregation occurred during or after purification of the RNA
      by sucrose gradient centrifugation and alcohol precipitation and was dependent
      upon the presence of a protein apparently bound covalently to a region at or near
      the 5' terminus of the viral RNA. This protein is probably the VPg. The RNAs of
      tobacco mosaic virus and cowpea mosaic virus did not form aggregates when
      isolated from purified virus by similar procedures.

PMID- 1990065
TI  - The tobacco mosaic virus 30K movement protein in transgenic tobacco plants is
      localized to plasmodesmata.
AB  - Transgenic tobacco plants expressing a gene encoding the tobacco mosaic virus
      (TMV) movement protein (30K) were studied using immunocytochemical techniques.
      The movement protein was shown to be localized within or on most of the
      plasmodesmata observed in the transformed plant. These results are consistent
      with the idea that the movement protein interacts with the plasmodesmata to
      facilitate the cell-to-cell spread of TMV.

PMID- 1990066
TI  - Nucleotide sequence of RNA 2 of a Czechoslovakian isolate of red clover necrotic
      mosaic virus.
AB  - The complete nucleotide sequence (1448 nucleotides) of RNA 2 of a Czechoslovakian
      isolate TpM-34 of red clover necrotic mosaic virus (RCNMV-TpM-34) has been
      determined. The sequence contained one major open reading frame (ORF) with the
      potential to encode a protein of 326 amino acids (Mr 35755), designated P2. The
      nucleotide sequence of RNA 2 of RCNMV-TpM-34 and the previously published
      sequence of RNA 2 of an Australian isolate of the virus (RCNMV-Aus) were 83%
      identical and there was 80% amino acid sequence identity between the P2 proteins
      of these isolates. However the N-terminal two-thirds of the P2 proteins shared a
      higher degree of similarity than the C-terminal regions which were predicted to
      have a more flexible structure. An ORF in the 3' portion of RNA 2 of RCNMV-Aus,
      which could encode a protein of Mr 5000, was not present in RNA 2 of RCNMV-TpM
      34. RNAs 1 and 2 of RCNMV-TpM-34 and RCNMV-Aus are bilaterally compatible.

PMID- 1990067
TI  - Proteins of bovine ephemeral fever virus.
AB  - The proteins of bovine ephemeral fever virus (BEFV) were examined in purified
      virions and in infected BHK-21 cells. Five structural proteins were named L
      (180K), G (81K), N (52K), M1 (43K) and M2 (29K). The 81K G protein incorporated
      [3H]glucosamine, was removed from virions by treatment with Triton X-100 and
      bound monoclonal antibodies which were both neutralizing and protective.
      Treatment of virions with Triton X-100 and 0.2 to 1.0 M-NaCl progressively
      released L, M1 and M2. The N protein remained associated with nucleocapsids in up
      to 2.5 M-NaCl. The glycoprotein (G), nucleoprotein (N) and matrix protein (M2)
      were phosphorylated. In BEFV-infected BHK-21 cells, five virus-induced proteins
      were detected from 12 h post-infection. The L, N, M1 and M2 proteins corresponded
      to those detected in virions whereas the G protein existed in two forms. In
      tunicamycin-treated cells these occurred as 67K and 71K non-glycosylated
      precursors. In the absence of tunicamycin, 77K and 79K glycosylated forms were
      further modified to produce the 81K virion G protein and a 90K cell-associated
      form. Five viral proteins were also detected in cells infected with the closely
      related Berrimah virus; the Berrimah virus G protein was also present in two
      forms.

PMID- 1990068
TI  - Deduced amino acid sequence of the fusion glycoprotein of turkey rhinotracheitis
      virus has greater identity with that of human respiratory syncytial virus, a
      pneumovirus, than that of paramyxoviruses and morbilliviruses.
AB  - The sequence of the fusion (F) glycoprotein of turkey rhinotracheitis virus
      (TRTV) has been deduced from cDNA clones derived from oligo(dT)-selected infected
      cell RNA. The protein consists of 538 amino acids, the F2 and F1 subunits
      containing 102 (including the F2-F1 connecting peptide RRRR) and 436 residues,
      respectively. Each subunit has one potential N-linked glycosylation site. The
      protein has 38 to 39% amino acid identity with the F protein of respiratory
      syncytial virus (Pneumovirus genus) but only about half that with members of the
      other two genera (Paramyxovirus and Morbillivirus) in the Paramyxoviridae family.
      This is the first sequence evidence to support the view that TRTV is a
      pneumovirus, the first avian member of the genus to be described.

PMID- 1990069
TI  - Identification of several different lineages of measles virus.
AB  - The sequences of a region of the nucleocapsid protein gene, between nucleotides
      1231 and 1686, encoding the C-terminal 151 amino acid residues of the
      nucleocapsid protein have been determined for 16 strains of measles virus.
      Analysis of this region showed that it is highly divergent (up to 7.2% divergence
      in the nucleotide sequence and 10.6% divergence in the amino acid sequence
      between most distant strains) and that several lineages of measles virus can be
      found to co-circulate at a given time. Some of the lineages show geographical
      restriction. The results for measles virus are similar to those reported for
      other human paramyxoviruses such as mumps virus, parainfluenza type 3 virus and
      the avian Newcastle disease virus.

PMID- 1990070
TI  - The genome organization of potato virus M RNA.
AB  - The 8534 nucleotide sequence of the genome of the carlavirus, potato virus M
      (PVM), has been determined. The sequence contains six large open reading frames
      (ORFs) and non-coding regions consisting of 75 nucleotides at the 5' end, 70
      nucleotides followed by a poly(A) tail at the 3' end and 38 and 21 nucleotides
      between three large blocks of coding sequences. The ORF beginning at the first
      initiation codon at nucleotide 76 encodes a polypeptide of 223K which, according
      to its primary sequence analysis, seems to be a virus RNA replicase. The next
      coding block consists of three ORFs encoding polypeptides of 25K, 12K and 7K. The
      third block consists of two ORFs encoding polypeptides of 34K (PVM coat protein)
      and 11K. The 11K polypeptide contains a pattern resembling the consensus for a
      metal-binding nucleic acid-binding 'finger'.

PMID- 1990071
TI  - The "military family syndrome" revisited: "by the numbers".
AB  - Because concerns have been raised about high levels of psychopathology in
      military children, the authors used standardized psychopathology rating scales to
      survey 213 six-to twelve-year-old children of military parents and their parents.
      Results from children's symptom self-reports, as well as from teachers' ratings
      of children, indicated that children's symptom levels were at levels consistent
      with national norms. In contrast, parents' (especially mothers') ratings of
      children were significantly higher than national norms, as were parents' ratings
      of their own symptoms. Also, parents' own symptom reports showed somewhat
      stronger relationships with life stressors presumably affecting the child than
      did the children's and teachers' reports. Results suggest that parents' reports
      of children's symptoms may be mediated by the effects of military life stressors
      on the parents, but these stressors do not necessarily result in higher symptoms
      in the children. Overall results do not support the notion that levels of
      psychopathology are greatly increased in children of military parents. Further
      studies of military families should address the effects of rank and socioeconomic
      status, housing, and the current impact of life stressors on the parents as well
      as the children in order to avoid drawing erroneous conclusions about parts or
      all of the military community.

PMID- 1990072
TI  - Effectiveness in psychiatric care. I. A cross-national study of the process of
      treatment and outcomes of major depressive disorder.
AB  - Recent research suggests that, despite the development of effective psychiatric
      treatment, there is marked underuse of care. This pilot study had the objective
      of dissecting the process of care in an attempt to understand outcomes for
      patients with major affective disorder and for their families. Twenty-four
      patients with a DSM-III diagnosis of major affective disorder were identified 12
      to 18 months after hospital admission in three countries (Italy, Japan, and the
      United States). The patients, their families, and their doctors were interviewed
      separately and then together, using instruments measuring delivery of treatment
      (using an ideal treatment criteria set) and percentage of achievement of
      treatment goals. These measures were then (using parametric and nonparametric
      statistics) correlated with resolution of the index episode and the patient's
      global outcome (using the Global Assessment Scale). The data demonstrated that
      physicians delivered about half (52%) and, subsequently, achieved about half
      (54%) of what would be considered ideal care to patients and other family
      members. The mean resolution of the index episode at follow-up was only 3.0 (on a
      0- to 5-point scale). There was a significant positive association between the
      most important outcome measure, i.e., the resolution of the episode, and the
      achievement of treatment goals for both the patient (p less than .07) and the
      family (p less than .005). Patients and families with the best resolutions
      received significantly more good treatment than those with the worst resolutions
      (p less than .02), most notably with regard to medication (p less than .002).

PMID- 1990073
TI  - Characteristics and long-term follow-up of patients hospitalized for mood
      disorders in the Phipps Clinic, 1913-1940.
AB  - From a sample of 2809 mood disorder patients hospitalized between 1913 and 1940,
      we selected for detailed study 914 patients with at least a 5 year follow-up and
      103 patients who committed suicide within 5 years of discharge. Patients with
      clearly mood incongruent delusions or an onset associated with a physical illness
      were excluded. Based on the presence or absence of manic symptoms, this cohort of
      1017 cases was divided into 297 bipolar and 945 unipolar patients. Bipolar
      patients had an earlier age of onset and admission and were more likely to be
      delusional and hallucinated. They also had more sudden onsets, more previous
      admissions, worse premorbid characteristics, and more problems with alcohol, but
      more patients were discharged as recovered. Unipolar patients were more often
      female and married, more likely to have made previous suicidal attempts, and more
      likely to have experienced a precipitating event. On a mean follow-up of 13.5
      years, only 11% of the bipolar and 22% of the unipolar patients experienced no
      further episodes of mania or depression. Of the bipolar group, 77% had to be
      rehospitalized, as did 56% of the unipolars. Only 2% of the sample had manic
      episodes with no lifetime depressions; this small group had the best outcome. One
      third of all the patients were rated unimproved on follow-up. Thirteen percent
      committed suicide, usually within 1 year of discharge. Bipolar patients had the
      worst outcome, with 43% rated unimproved. The sample was split by odd or even
      case number and one half was used to construct a prognostic scale significantly
      correlated with long-term outcome. It was cross-validated on the other half of
      the sample with little shrinkage. Patients with non-drug-treated affective
      disorders hospitalized half a century ago were found to have polyepisodic
      illnesses with a frequently chronic course.

PMID- 1990075
TI  - Outpatient commitment for "revolving door" patients: compliance and treatment.
AB  - This paper describes the use and effectiveness of outpatient commitment in
      inducing compliance with treatment among chronically mentally ill "revolving
      door" patients, those who recurrently become dangerous and revolve though civil
      commitment courts as well as state mental hospitals. Patients characteristics,
      treatment modalities, and mental health center actions to ensure compliance are
      described. Comparison of those patients ordered to outpatient commitment with
      those having other court dispositions (involuntary hospitalization and release)
      indicates that outpatient commitment induces compliance and leads to treatment
      maintenance even after the court order terminates.

PMID- 1990074
TI  - Effect of personality disorders on outcome of treatment.
AB  - Although many clinicians have long believed that personality pathology may
      interfere with the effectiveness of treatment of axis I disorders, until recently
      there were no empirical studies on the subject. This report reviews the recent
      literature with regard to the following questions: a) Does personality pathology
      predict negative outcome of treatment for axis I disorders? b) If so, are there
      specific personality traits or disorders that account for such a negative
      outcome? The literature review reveals a robust finding that patients with
      personality pathology have a poorer response to treatment of axis I disorders
      than those without such pathology. Specific axis I disorders reported on include
      DSM-III major depression, panic disorder, and obsessive-compulsive disorder. Both
      inpatients and outpatients have been studied. There is too little literature to
      determine whether certain pathological personality traits are especially
      important, but there is enough to provide methodological guidance for future
      studies. Such studies should use standardized measures of personality and
      outcome, should match personality and nonpersonality groups on severity of the
      axis I disorder, and should be certain that axis I diagnoses are not confounded
      by axis II symptoms.

PMID- 1990076
TI  - Designing drug efficacy trials in the treatment of cocaine abuse.
AB  - A variety of pharmacological approaches have been introduced to reduce cocaine
      craving and use. Most of these have been tested in open-label, noncontrolled
      trials; there is a need for more definitive placebo-controlled investigations. An
      overview of research design issues involved in the planning of such studies is
      presented. Discussion of the potential aims of drug trials and the basic
      principles of methodology and data analysis is intended to facilitate the
      undertaking of such studies by clinicians in the field of substance abuse as well
      as by clinical researchers not currently working in substance abuse.

PMID- 1990077
TI  - Psychophysiological responses in the diagnosis of posttraumatic stress disorder
      in Vietnam veterans.
AB  - In one sample of 104 male Vietnam combat veterans, we found that five heart rate
      parameters from a psychophysiological assessment could correctly discriminate 75%
      of the sample into those with PTSD and those without it. Using a stepwise
      approach, we found adding 10 blood pressure parameters increased discrimination
      to 80%, while adding five parameters from frontal electromyograms did not
      increase discrimination. Cross-validation of the heart rate parameters on a new
      sample of 96 veterans resulted in 83% correct discrimination.

PMID- 1990078
TI  - Organizational change toward a nursing agenda. A framework from the Strengthening
      Hospital Nursing Program.
AB  - Although nursing is central to most efforts aimed at changing U.S. hospitals and
      care delivery systems, little is known within the profession about initiating or
      participating in large system--total hospital--change. Using data from the
      national Strengthening Hospital Nursing Program, a program supported by the
      Robert Wood Johnson Foundation and The Pew Charitable Trusts, the authors explore
      what organizational factors are relevant for hospital change that is systemic,
      ambitious, and favorable to a nursing agenda.

PMID- 1990079
TI  - The University Hospital Nurse Extender Model. Part II, Program implementation.
AB  - This second article in a four-part series provides a detailed discussion of each
      phase of the implementation process, along with a demographic summary of the
      University Hospital Patient Care Technicians' Program 2 years after program
      implementation. Part I provided the overview and conceptual framework for the
      model. Parts III and IV will present the results of a year-long evaluation of the
      model and the lessons learned during the implementation process.

PMID- 1990080
TI  - The cost of nursing excellence in critical care.
AB  - The results of the American Association of Critical-Care Nurses Demonstration
      Project support the contention that high quality critical care nursing can be
      provided to patients at a reasonable cost. In addition, the data refute the
      notion that elements influenced by nurses--supplies and nursing care--are the
      most costly portion of the total hospital charge.

PMID- 1990081
TI  - Outcomes of power development in work relationships.
AB  - Nurse executives who routinely feel overpowered in their work relationships are
      highly stressed. When high levels of stress are experienced regularly, ill health
      may be the outcome, resulting in negative consequences for both the nurse
      executive and the organization. Strategies are proposed for nurse executives to
      use in coping with consistent patterns of work-related overpowerment.

PMID- 1990082
TI  - Redesigning management roles. The executive challenge.
AB  - The revolutionary changes that have occurred in healthcare during the past decade
      challenge nurse executives to analyze and redesign managerial roles. To confront
      future change and developments in nursing and management practice, the role of
      the first-line nurse manager must take on new dimensions to facilitate quality
      outcomes in patient care and empowerment of nurses at all levels of practice. The
      author presents a model of job redesign for nurse managers with emphasis on the
      motivational approach. Role outcomes for nurse managers are also detailed.

PMID- 1990083
TI  - The impact of information systems on nursing performance and productivity.
AB  - Recent technologic developments have expanded the capabilities of information
      systems to enhance nursing communication, documentation, and clinical decision
      making. The author discusses the potential of sophisticated information systems
      to improve nursing performance and productivity and to affect positively clinical
      outcomes, patient satisfaction, nursing retention, and strategic planning
      capabilities. Information systems can serve as a remarkable vehicle for
      efficiently enhancing quality of care in an environment of stringent cost
      constraints.

PMID- 1990084
TI  - Supporting nurse managers.

PMID- 1990085
TI  - Dealing with drugs.

PMID- 1990086
TI  - Mandibular ramus anatomy as it relates to the medial osteotomy of the sagittal
      split ramus osteotomy.
AB  - The sagittal split ramus osteotomy is probably the most frequently used procedure
      for correction of mandibular skeletal dentofacial deformities. Despite numerous
      improvements in the technique in the 30 years since the procedure was introduced,
      a number of troublesome complications still occur. These include unfavorable
      fracture during surgery, paresthesia, and relapse. The purpose of this study was
      to determine where fusion of the buccal and lingual cortical plates occurs in the
      upper mandibular ramus, as it is thought that placement of the horizontal medial
      osteotomy above the point of fusion (without any intervening medullary bone) may
      lead to unfavorable fracture during splitting. Forty-nine human mandibles were
      sectioned vertically at three locations perpendicular to the surface of the ramus
      and the occlusal plane. Measurements were made to locate vertically the point of
      fusion of the buccal and lingual cortical plates relative to the lingula and to
      the depth of the sigmoid notch. The point of fusion occurred between 7.5 and 13.3
      mm above the lingula. Only 2% of mandibles had fusion at or below the level of
      the lingula in the anterior ramus, whereas in the posterior ramus, 6.1% of
      mandibles were fused at that level. At a level halfway from the lingula to the
      sigmoid notch, 20% of mandibles were fused in the anterior ramus, whereas in the
      mid- to posterior ramus, the incidence was as high as 39%. The location of the
      medial horizontal osteotomy should be at or just above the tip of the lingula. A
      higher level of cut may be associated with an increased difficulty in splitting
      or incidence of unfavorable fracture.

PMID- 1990087
TI  - Outpatient orthognathic surgery: criteria and a review of cases.
AB  - Over a 9-year period, 87 orthognathic procedures were performed in an outpatient
      environment. Procedures performed included horizontal mandibular osteotomies,
      rapid palatal expansions, bilateral sagittal split osteotomies, posterior and
      anterior maxillary osteotomies, and Le Fort I osteotomies. Fourteen of these
      patients were subsequently admitted to a hospital for either observation or full
      inpatient care. The rates of admission varied for each of the procedures, with
      length of anesthesia statistically related to the frequency of admission. Patient
      selection criteria and facilities used are reviewed.

PMID- 1990088
TI  - Evaluation of the serum level of immunosuppressive substance in oral cancer
      patients.
AB  - The serum level of immunosuppressive substance (IS) was studied in 40 patients
      with primary oral cancer and in 79 patients without cancer. Its usefulness was
      evaluated as a parameter for monitoring therapy as well as recurrence of the
      tumors. Mean values for serum IS in patients with cancer and patients without
      were 687 +/- 284 micrograms/mL and 464 +/- 153 micrograms/mL, respectively.
      Normal healthy controls had a mean value of 431 +/- 105 micrograms/mL, with the
      cutoff value set at 641 micrograms/mL (mean +2 SD). Patients without cancer who
      had a severe infectious disease showed conspicuously high serum IS levels, and
      these values were closely correlated with their C-reactive protein values. The
      positive rate of IS increased in all patients with oral cancer was 58%. The mean
      level of serum IS in cancer patients was significantly higher than that of the
      controls (P less than .01), and the level was found to be more elevated as the
      stage of the disease advanced (stage I to III, 48%; stage IV, 68%). Histologic
      analysis of the tumor cells in patients with squamous cell carcinoma (SCC) showed
      that the mean serum IS level of those who had poorly differentiated SCC was much
      higher (937 +/- 181 micrograms/mL) than that of patients with well-differentiated
      SCC (616 +/- 159 micrograms/mL). Patients who had recurrent or metastatic cancer,
      or those who died from the cancer exhibited marked elevation of the serum IS
      levels, whereas patients who remained free of cancer in the follow-up period
      showed significantly lower serum IS levels. The rise and fall of the serum IS
      level was closely correlated with the disease progression and/or remission. These
      data strongly suggest that serum IS is a useful parameter for monitoring the
      disease stage as well as the effect of therapy on patients with oral cancer.

PMID- 1990089
TI  - Extraoral parotid sialolithotomy.
AB  - The extraoral approach to duct surgery for the removal of parotid stones can be a
      simple procedure once the stone is accurately located in relation to the skin
      surface. The combination of sialography and sonography can provide this
      information. A case report demonstrates the step-by-step approach to diagnosis,
      localization, and surgery for the management of such extraglandular sialoliths.

PMID- 1990090
TI  - Indications for simultaneous orthognathic and septorhinoplastic surgery.
AB  - Orthognathic and rhinoplastic surgery can be combined successfully when certain
      guidelines are understood. Relative indications and contraindications have been
      established that generally yield predictable results. Tip position (rotation and
      projection) may be the most difficult aspect to predict and, therefore, is best
      avoided during simultaneous surgery. Major deformities of the dorsum can be
      easily corrected in conjunction with maxillary surgery. Three cases demonstrating
      these guidelines are presented and discussed.

PMID- 1990091
TI  - The relationship between the indications for the surgical removal of impacted
      third molars and the incidence of alveolar osteitis.
AB  - Six hundred forty-two impacted third molars were surgically removed in 412
      patients. Before surgery, each patient was assessed clinically and
      radiographically, and the reason for the removal of each tooth was specifically
      recorded. One hundred eighty-two of the impacted teeth were removed for
      prophylactic reasons and 460 for therapeutic reasons. As much as possible,
      standardization of the operating procedure and environment, and of the
      preoperative and postoperative regimens was observed. After surgery, each case
      was followed to determine the absence or presence of signs and symptoms of
      alveolar osteitis. It was found that several factors seem to contribute to the
      development of alveolar osteitis; however, the most significant related finding
      was that the reason for the extraction, that is, whether the extraction was
      undertaken for therapeutic or prophylactic reasons.

PMID- 1990092
TI  - Evaluation of ultrasound in the diagnosis of pathologic processes in the parotid
      gland.
AB  - The values of ultrasound in differentiation of pathologic processes in the
      parotid gland were studied in 61 patients. The ultrasound findings were compared
      with operative and histologic findings. In 28 patients with chronic inflammatory
      processes, the ultrasound findings were in complete correlation with the
      histologic findings, showing enlarged parotid glands, homogenous glandular
      epithelium, and small, multiple cysts. In 31 patients with a tumor of the parotid
      gland, ultrasound scanning detected the presence of the tumor. In determining the
      location of the tumor, the method is highly specific when it is localized in the
      superficial lobe (100%), and it is less specific when it is localized in the deep
      lobe of the parotid gland. Also, it is highly specific in determination of tumor
      size (96%). In two cases with retention cysts, the ultrasound findings also
      correlated with the histologic and operative findings. The results obtained show
      that ultrasound is a reliable diagnostic method for detection of pathologic
      changes in the parotid gland.

PMID- 1990093
TI  - Arthroscopic treatment of temporomandibular joint locking resulting from disc
      derangement: two-year results.
AB  - This article reports 2-year postarthroscopic surgical treatment data for 18
      subjects (17 female and 1 male) who had a diagnosis of restricted mandibular
      movement due to an internal derangement of the temporomandibular joint (TMJ).
      These subjects had been treated by an average of 2.1 +/- 1.1 doctors for their
      TMJ problem before seeing the surgeon for arthroscopic treatment. The subjects'
      mean pain score at the final time point (21 to 30 months after surgery) was
      decreased by 57% in usual pain intensity. Jaw function showed an average
      improvement of 67%. These subjects also showed a 13-mm mean increase in their
      maximum active opening ability at the 2-year postsurgical time point. Slight to
      definite clicking noises were present presurgically in 11 of 18 patients, and
      similar joint noises were reported in 14 of 18 patients postsurgically. The mean
      overall improvement was rated as 8.18 +/- 2.4, with 10 the highest possible
      rating. One subject rated her improvement as 0, two subjects rated their
      improvement as 6 out of 10. No significant morbidity was reported by the subjects
      as a result of their surgery.

PMID- 1990094
TI  - Preoperative laboratory testing for the oral and maxillofacial surgery patient.
AB  - Studies estimate that approximately 60% of preoperative testing could be
      eliminated without adversely affecting patient care. Unnecessary testing tends to
      cause extra risk to the patient, inefficient operating room schedules, and
      unnecessary costs. These extra tests may be hazardous to patients because of the
      pursuit and treatment of borderline positive or false-positive results.
      Furthermore, extra testing may also increase medicolegal risk, because the
      abnormalities that are discovered are usually not noted on the chart. A reliable
      and effective method for ordering laboratory tests to assess patients
      preoperatively and reduce morbidity and cost is presented.

PMID- 1990095
TI  - An acquired arteriovenous fistula secondary to temporomandibular joint
      arthroscopy: report of a case.

PMID- 1990096
TI  - Removal of a retromaxillary schwannoma via a temporal approach.

PMID- 1990097
TI  - Bilateral antral mucoceles: a report of a case.

PMID- 1990098
TI  - Neurilemmoma of the mental nerve.

PMID- 1990099
TI  - First branchial cleft anomaly: a case report.

PMID- 1990100
TI  - Sinus histiocytosis with massive lymphadenopathy: a case with facial bones
      involvement.

PMID- 1990101
TI  - A simplified method for identification of maxillomandibular fixation wires.

PMID- 1990102
TI  - A misunderstanding about fixation methods after floor of mouth plasty procedures.

PMID- 1990103
TI  - Home antibiotic therapy for brain abscesses.

PMID- 1990104
TI  - Erroneous laboratory values obtained from central catheters.
AB  - Serious analytic errors in potassium measurements have been identified in blood
      specimens obtained from newly inserted central catheters. Erroneous elevated
      readings have been related to interactions of chemistry analyzer electrodes and
      substances fixed to external and intraluminal walls of the central catheter.
      Anecdotal summaries of this phenomenon are presented to enable the nurse to
      recognize potential problems when sampling blood from central catheters. Studies
      were performed to determine the amount of flush necessary to clear the catheter
      of interfering residue. To eliminate this potentially hazardous occurrence,
      recommended flush volumes, nursing implications, and actions are described.

PMID- 1990105
TI  - A pharmacokinetic primer for intravenous nurses.
AB  - Traditionally, drug doses and intervals between doses have been empirically
      decided by prescribers. Doses and intervals were subsequently adjusted based on
      observed efficacy or toxic effects. In the absence of consistent clinical
      findings or when the disease being treated is episodic in nature, such as in the
      case of asthma or epilepsy, optimal dosing is difficult to achieve. An
      alternative approach is the adjustment of doses based on the concentration of
      drugs in plasma. This approach has come to be called therapeutic drug monitoring,
      or TDM. To make adjustment of doses more efficient, mathematical models have been
      developed that describe and predict drug concentrations in various body fluids.
      These mathematical models incorporate pharmacokinetic parameters, such as volume
      of distribution, absorption rate constant, and clearance, which, when known for a
      particular patient or group of patients, allow judicious adjustment of doses of
      drugs that might otherwise be ineffective. This article reviews the model most
      commonly used in TDM and explains the parameters associated with it. It also
      considers the importance of TDM in clinical practice and the role of the nurse in
      this aspect of patient care.

PMID- 1990106
TI  - Continuous subcutaneous infusions for pain control.
AB  - Chronic moderate-to-severe pain is a common problem that directly impacts on the
      quality of life of the patient with a malignant neoplasm. It is estimated that
      pain is a major symptom in 70% of cancer patients. Continuous subcutaneous
      infusion of opioids has proved to be an efficacious and safe method to control
      the chronic pain of the home-bound and hospitalized patient. A wide variety of
      opioids can be used, including morphine, hydromorphone, and methadone. The
      subcutaneous route offers economic as well as physiologic advantages. The primary
      disadvantage to the system is volume limitations. Competent nursing management of
      the subcutaneous infusion helps to maximize the effectiveness of the opioid,
      thereby improving the patient's quality of life.

PMID- 1990107
TI  - Shared governance. Opportunities for intravenous nurses.
AB  - Intravenous nurses must find their work both satisfying and fulfilling,
      emotionally and professionally. Autonomy is a vital component of long tenure and
      satisfaction. Nurses need to get involved in decision making, setting standards,
      and ensuring quality. Shared Governance, a professional nursing practice model,
      provides the structure for accountability for nursing practice and participation
      in the process. I.V. nurses have a unique opportunity to be in the leadership
      forefront because of their mobility and visibility within their institutions.

PMID- 1990108
TI  - State coalition councils. Intravenous nursing involvement.
AB  - Many states have developed a nursing organization of a different nature--a
      coalition of representatives from all specialties within the nursing profession.
      These coalitions have opened new avenues for coordinated actions among all
      nursing organizations. The Intravenous Nurses Society's legislative network has
      opened new doors for opportunity for legislative representatives on the local
      level. When combined, these two forces can result in many positive changes for
      the profession of nursing.

PMID- 1990109
TI  - Television: we need to watch it!

PMID- 1990110
TI  - Tuberculosis screening and treatment in children.
AB  - Tuberculosis continues to be a major health care problem in the world, especially
      among children. In the United States, health care providers rely heavily on
      routine skin testing to identify cases of tuberculosis. Pediatric nurse
      practitioners have the opportunity to recognize high-risk children, teach
      preventive health practices to patients and families, and thus to decrease
      morbidity from the disease. This article presents an overview of the incidence of
      the disease, as well as the causes, pathophysiology, epidemiology, diagnosis and
      management of tuberculosis.

PMID- 1990111
TI  - Chronic pain and the child with juvenile rheumatoid arthritis.
AB  - This article presents a summary of nursing issues concerning the assessment and
      management of pain in children with juvenile rheumatoid arthritis (JRA).
      Following a brief description of the difference between acute and chronic pain
      and a description of JRA, the developmental issues relating to pain assessment in
      this population are discussed. Three pain assessment tool alternatives are
      presented. Finally, current strategies for pain relief and treatment of children
      with JRA are presented.

PMID- 1990112
TI  - Cystic fibrosis, intravenous antibiotics, and home therapy.
AB  - The survival rate of patients with cystic fibrosis has improved considerably in
      the last 20 years. Although not all of the factors accounting for this change are
      understood, aggressive nutritional management and treatment of pulmonary
      exacerbations certainly play a role. Home intravenous (IV) antibiotic delivery
      for pulmonary exacerbation has proved to be as effective as hospital treatment
      and offers significant advantages to the patient and family. This article
      examines the microbiology of pulmonary infections in patients with cystic
      fibrosis, as well as antimicrobial therapy, methods of IV administration, home IV
      therapy, and the nurse practitioner's role in this home program in the future.

PMID- 1990113
TI  - Physiologic sequelae of prematurity: the nurse practitioner's role. Part IV.
      Anemia.
AB  - Anemia in the immediate newborn period may be caused by hemolysis, by a failure
      of red-cell production, or by a combination of both. However, anemia of
      prematurity often is the result of hemolysis, of a lack of erythropoietin, and/or
      of nutritional deficits. Transfusion without a search for the cause may obscure
      the underlying pathology of the anemia. Because severe anemia can be life
      threatening, prompt diagnosis and treatment are required. In this article, the
      fourth of a series of articles on the sequelae of prematurity, a discussion of
      the pathophysiology, signs and symptoms, data collection, treatment modalities
      pertinent to the anemia of prematurity, and parental education are discussed.

PMID- 1990114
TI  - The Port-A-Cath and Per-Q-Cath.
AB  - Venous access in acute and chronically ill patients can become problematic when
      attempting to maintain a reliable system. The need for safe and dependable
      intravascular systems has become quite evident. This article examines the Port-A
      Cath (Pharmacia, Inc., St. Paul, MN) and the Per-Q-Cath (Gesco International,
      Inc., San Antonio, TX). These systems are preferred by several patient
      populations who require frequent or prolonged intravenous therapy.

PMID- 1990115
TI  - A school-based clinic in a preschool.
AB  - Primary health care in a school-based clinic (SBC) for preschoolers is examined.
      Based on personal experience, a PNP describes an actual preschool SBC. The
      benefits of an on-site service for this age group include periodic and accurate
      developmental assessments and screening procedures and improved compliance with
      treatments and referrals. The process of establishing an SBC is presented in
      terms of management, funding, and resources.

PMID- 1990116
TI  - Dietary consultation for lactating women.

PMID- 1990117
TI  - Alopecia.

PMID- 1990118
TI  - Federal reimbursement to nurse practitioners.

PMID- 1990119
TI  - Methodological issues in conducting research on parent-infant attachment.
AB  - The study of the parent's attachment to his or her infant has recently become a
      research topic of great interest to parent-child nursing practitioners. The
      parent-infant relationship has been examined using a variety of methodological
      approaches. Brazelton Neonatal Behavioral Assessment Scale demonstrations, home
      and laboratory observations, process recordings, videotape analyses, self
      reported questionnaires, and developmental screening tools have all been used by
      researchers to measure the quality of this earliest form of human attachment.
      However, there are rising concerns as to the validity of attachment research in
      general, as well as methodological limitations in collecting data on parent
      infant interactions. This article discusses issues of methodological concern in
      attachment research and makes suggestions to strengthen validity.

PMID- 1990121
TI  - Disclosure.

PMID- 1990120
TI  - Studying infant and toddler play.
AB  - The play of infants and toddlers is a rich and flexible research modality. Play
      assessment can be an outcome measure of cognition or social ability, or it can be
      measured in conjunction with related constructs such as language to give a broad
      view of early development. Play can also be an effective intervention in studies
      of cognition, language, motor, or social development. This article offers
      strategies for the researcher who is interested in infant and toddler play.
      Emphasis is placed on environmental variables that the researcher manipulates to
      optimize the child's performance. Play measures are briefly addressed.

PMID- 1990122
TI  - Methodological issues in child sexual abuse research.
AB  - Research has only recently documented the negative effects of child sexual abuse.
      Investigators attempting to validate empirically the stress responses of children
      to sexual abuse are confronted with many methodological issues, including those
      related to measurement, sample selection, use of comparison subjects, and legal
      and ethical considerations. This article discusses methodological issues that
      need to be considered when designing and implementing studies on the impact of
      child sexual abuse. Suggestions are made for strengthening research designs, and
      several studies that have incorporated some of these suggestions are reviewed.
      Recommendations are made for areas that nurse researchers may want to explore in
      the future, such as parental and sibling response to sexual victimization,
      characteristics of children that may ameliorate the effects of sexual abuse, and
      children's responses to examination of the genitalia.

PMID- 1990123
TI  - Achieving reliability in observational research: lessons from a study of newborn
      temperament.
AB  - Observational studies of human responses frequently yield only tenuous or no
      support for hypothesized relationships. These null findings often may be due to
      reliance on single observations rather than on multiple measures aggregated over
      contexts or occasions. This article discusses the principle of aggregation and
      describes the development and evaluation of aggregated measures in a study of the
      relationship of nursery nurse's behavior to emerging newborn temperament.

PMID- 1990124
TI  - Methodological issues for adolescent pregnancy research.
AB  - Nurses have long been in the forefront of health care delivery for adolescents
      and are becoming more involved in adolescent pregnancy research. This article
      focuses on six methodological issues for adolescent pregnancy research:
      formulating the research question, selecting appropriate measures, recruiting
      subjects, obtaining informed consent, categorizing socioeconomic status, and
      balancing the clinician-researcher relationship. As we prepare for the 21st
      Century, we must develop new and creative approaches to adolescent pregnancy
      research, and we must bridge the gap between research and practice. Ultimately,
      knowledge derived from research and clinical practice should generate
      comprehensive health care and social policies for dealing with adolescent
      pregnancy.

PMID- 1990125
TI  - Application of the life-span developmental perspective to nursing research with
      adolescents.
AB  - Phenomena of interest to nurse researchers include the responses of persons
      across the life span to changes in their lives related to conditions of health
      and illness. The topic of this article is the life span stage known as
      adolescence, and the article is grounded in the premise that questions related to
      the effects of chronic illness at different points in the adolescent life course
      (i.e., early, middle, and late adolescence) are best studied from a life-span
      developmental perspective. First, the traditional developmental theories, the
      commonly held world views from which they emerged, and their relative
      contributions to research with adolescents are reviewed. The life-span
      developmental perspective is then discussed, with particular emphasis on its
      usefulness in guiding research aimed at answering questions that address change
      in the behavioral responses of adolescents to conditions of health and illness.

PMID- 1990126
TI  - The substance-abusing family: consideration for nursing research.
AB  - Investigations to explore and document the characteristics of addicted families
      are possible for nurse researchers in a variety of settings. Addicted families
      can be identified through hospitals, clinics, or community substance abuse
      treatment centers. Confidentiality issues must be addressed with carefully
      designed consent forms. A thorough understanding of addicted family systems is
      essential. System, role, and family theories provide a framework for
      understanding the influence of substance abuse on all family members.
      Anticipation of common social, economic, and criminal crises of addicted families
      will assist the researcher to avoid conflicts between research and service.
      Methodological limitations are common in research with addicted families, but
      well-designed, descriptive studies with small- to moderate-sized self-selected
      samples can add greatly to our nursing knowledge base over time.

PMID- 1990127
TI  - Mentoring the novice nurse researcher.

PMID- 1990128
TI  - Growing up in hatred.

PMID- 1990129
TI  - Health goals for children and their families: 1991 and beyond.

PMID- 1990130
TI  - The Landry Vein Light: increasing venipuncture success rates.

PMID- 1990131
TI  - Creating a positive impact on the health and well-being of children and families
      through education.

PMID- 1990132
TI  - Pediatric nursing in Taiwan.

PMID- 1990133
TI  - Women and children first?

PMID- 1990134
TI  - A rapid method for identification of Mycobacterium species by polyacrylamide gel
      electrophoresis of soluble cell proteins.
AB  - The sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE)
      profiles of an easily and rapidly prepared soluble protein fraction were used in
      conjunction with conventional techniques to identify different strains of
      Mycobacterium tuberculosis, M. bovis, M. bovis BCG, M. africanum, M. avium, M.
      kansasii, M. marinum, M. gastri, M. simiae and M. malmoense. Complete concordance
      of results from both methods was obtained with all species except those of the M.
      tuberculosis complex. With the SDS-PAGE technique, all strains of the M.
      tuberculosis complex were recognised as belonging to one species. By visual
      analysis of the SDS-PAGE polypeptide profiles, only minor differences between
      strains of the same species were seen and each species showed a characteristic
      polypeptide profile. Quantitation of the data by calculation of the Dice
      coefficient of similarity of the band positions obtained by densitometry
      indicated that the similarity between different strains of one species was 90
      100% and the similarity between the species was in the range 30-45%. The results
      indicate that SDS-PAGE is a simple and rapid method for identifying mycobacterial
      strains.

PMID- 1990135
TI  - A rapid micro-agglutination technique for the detection of antibody to Legionella
      pneumophila serogroup 5.
AB  - A rapid micro-agglutination test (RMAT) for the detection of antibody to
      Legionella pneumophila serogroup 5 is described. It was found to be both
      sensitive and specific when compared with the indirect immunofluorescence test.
      Evaluation of 89 paired sera from patients with respiratory symptoms showed that
      the incidence of L. pneumophila serogroup 5 respiratory infection in East Anglia
      is low: only one case was found in this study. The RMAT would be easy to perform
      as a screening test in a routine serological laboratory.

PMID- 1990136
TI  - Antibiotic-resistant oral streptococci in dental patients susceptible to
      infective endocarditis.
AB  - The aim of this study was to determine the incidence of amoxycillin and
      erythromycin resistance in oral streptococci in patients at risk from infective
      endocarditis. Samples of gingival crevicular flora were taken from 65 patients at
      the site of dental treatment, prior to the prophylactic administration of
      amoxycillin (54 patients) or erythromycin (11 patients). Samples were also taken
      from 65 dental patients who were not considered to be at risk from infective
      endocarditis. No isolate had a minimum inhibitory concentration (MIC) of
      amoxycillin greater than 24 mg/L. However, erythromycin-resistant oral
      streptococci with MIC values greater than 3.5 mg/L were isolated from 22% of
      patients receiving amoxycillin prophylaxis, 9% of patients receiving amoxycillin
      prophylaxis, 9% of patients given erythromycin prophylaxis and 9% of patients not
      at risk from infective endocarditis. The antibiotic-resistant streptococci
      comprised mainly Streptococcus sanguis biotype II, although S. sanguis biotype I,
      S. mitis and S. salivarius were also frequently recovered.

PMID- 1990138
TI  - Genetic manipulation of Salmonella serotype Bovismorbificans to aromatic
      dependence and evaluation of its vaccine potential in mice.
AB  - The generation of smooth aromatic-dependent Salmonella serotype Bovismorbificans
      (Group C2, O6, 8) from a smooth wild-type parent strain by transduction with
      phage P1, and conjugation with Salmonella serotype Typhimurium carrying F'-8gal
      is described. The smooth aromatic-dependent S. serotype Bovismorbificans was non
      lethal for mice at an oral challenge dose of 2 x 10(9) cfu (equivalent to 200
      LD50 of the parent, wild-type strain). The safety of the auxotrophic mutant was
      further substantiated by comparing its multiplication kinetics in vivo with that
      of its virulent parent organisms. Mice immunised with live, smooth aromatic
      dependent S. serotype Bovismorbificans by either the oral or intraperitoneal
      (i.p.) route were protected against oral challenge with virulent S. serotype
      Bovismorbificans; the degree of protection was significantly better (p less than
      0.05) at a challenge dose of 100 or 200 LD50 in mice receiving two rather than
      one vaccination. In contrast, mice immunised with three doses of the formalin
      killed virulent, parent organisms by the i.p. route were not protected, in spite
      of high antibody titres. Only those mice immunised with the live, smooth aromatic
      dependent S. serotype Bovismorbificans i.p. developed significant (p less than
      0.01-0.05) delayed-type hypersensitivity.

PMID- 1990137
TI  - Assay of Bordetella pertussis heat-labile toxin with human embryonic lung cells.
AB  - An assay has been developed for Bordetella pertussis heat-labile toxin (HLT)
      based on morphological alterations in certain human embryonic lung (HEL) cell
      lines. Eighteen cell lines from human and other sources were tested but only two,
      MRC-5 and HELu2, were responsive to HLT. Confluent monolayers of the cells
      contracted within 24 h of exposure to the toxin, but without loss of viability
      during incubation for a further 3 days. The effect of HLT was quantitated by
      scoring the extent of morphological change, and by the decrease in Giemsa
      staining of the cell monolayers, as measured on an ELISA plate reader. This cell
      culture assay for HLT was more sensitive than lethality titration in mice but the
      dose-response curve had a lower slope. The specificity of the response was
      established by comparing unheated HLT with HLT heated at 56 degrees C, and with
      extracts from transposon-insertion mutants of B. pertussis which were deficient
      in HLT. Purified preparations of pertussis toxin and B. pertussis
      lipopolysaccharide gave no morphological response even at high doses.

PMID- 1990139
TI  - Factors affecting conjugative transfer of plasmid pWG613, determining gentamicin
      resistance, in Staphylococcus aureus.
AB  - Factors that are known to influence plasmid transfer in bacterial populations
      were studied for the conjugative plasmid pWG613, which determined gentamicin
      resistance in Staphylococcus aureus. The transfer frequency was largely
      unaffected over a wide range of temperature (18-42 degrees C); pH also had little
      effect on the transfer frequency in the range 5.0-8.5. High cell density and log
      phase cultures were required for optimal plasmid transfer, as were
      donor:recipient ratios of 0.003-3.3.

PMID- 1990140
TI  - The characterisation of clinical isolates of Staphylococcus aureus in Ile-Ife,
      Nigeria.
AB  - Of 166 strains of Staphylococcus aureus isolated from hospital patients and staff
      in Ile-Ife, Nigeria, 32% were non-typable (NT). The strains were isolated from
      skin lesions, eye infections, wounds and nasal flora. Isolates from skin lesions
      or eye and wound infections were more likely to produce protease (95% and 78%
      respectively) than nasal isolates (11%). Nearly all (99%) of the strains isolated
      were resistant to penicillin and 78% were resistant to tetracycline. Streptomycin
      resistance occurred in 25% of isolates; 19% were resistant to chloramphenicol and
      9% to methicillin.

PMID- 1990142
TI  - Eggs and Salmonella food-poisoning: an evaluation.
AB  - Evidence on the extent of the part played by infected hens' eggs in causing
      salmonella food-poisoning is inconclusive. The role of freshly cooked shell eggs
      is currently much exaggerated. Prevention should be sought through improved
      catering practices and kitchen hygiene, and attempts to eradicate salmonellas
      from laying flocks are likely to be ineffective.

PMID- 1990141
TI  - Antibodies to streptococcal opacity factor in a selected Indian population.
AB  - Antibody to at least one type of streptococcal opacity factor (OF) was present in
      39.0% of 235 selected subjects and, in 47.8% of these, to more than one type.
      Only 21.6% of children less than 4 years old had antibody to OF; these were to
      one type in 62.5% or to more than one in 37.5%. In the study group as a whole,
      the commonest antibodies were those to OF from M-serotype 25 followed, in
      descending order, by serotypes 4, 22, 2, 9, 48, 49, 28, 61 and 75. Patients with
      rheumatic fever or rheumatic heart disease most often had antibodies to OF from M
      types 25, 22, 4 and 9, whereas in patients with acute glomerulonephritis,
      antibodies to OF from M-types 48, 49 and 61 were commonest. The limitations of
      the OF-inhibition test as an epidemiological marker for prevalent M-types of
      group A streptococci are discussed.

PMID- 1990144
TI  - Immune response to Acinetobacter calcoaceticus infection in man.
AB  - After growth in an iron-depleted chemically-defined medium Acinetobacter
      calcoaceticus expressed four high mol. wt outer-membrane proteins (OMPs) which
      were repressed under iron supplementation or in a complex laboratory medium.
      Immunoblotting with serum from a septicaemic patient infected with A.
      calcoaceticus revealed antibody binding to these iron-repressible OMPs,
      indicating that they were expressed in vivo, and also to the 42- and 18-Kda OMPs.
      Although the antibody response to the OMPs did not vary significantly during
      convalescence, the response to the O-polysaccharide component of
      lipopolysaccharide decreased significantly. However, antibodies in serum from
      patients with A. calcoaceticus wound infections reacted with the iron repressible
      OMPs and a 54-Kda antigen suggesting a difference in immune recognition between
      local and systemic infection.

PMID- 1990143
TI  - Bacterial killing in vitro by abscess-derived neutrophils.
AB  - In the absence of antimicrobial therapy, bacteria such as Bacteriodes fragilis,
      Escherichia coli and Proteus mirabilis may persist within an intra-abdominal
      abscess in the presence of large numbers of neutrophils which, under optimal
      conditions in vitro, can readily phagocytose and kill the same bacterial strains.
      Neutrophils taken from abscesses induced by gram-negative bacteria such as those
      above contain viable organisms. On incubation in vitro in the presence of serum,
      these neutrophils kill the bacteria phagocytosed in the abscess poorly, if at
      all, yet can readily kill organisms added in vitro. To determine possible
      mechanisms that might explain this, we examined the bactericidal activity in
      vitro of neutrophils from a range of abscesses induced by one or two species of
      bacteria plus an abscess-potentiating agent, bran. The organisms studied were B.
      fragilis, E. coli, P. mirabilis and Staphylococcus aureus. The killing in vitro
      of E. coli and P. mirabilis, engulfed within an abscess, was significantly less
      than that of the same organisms when they were added to the in-vitro assay. In
      contrast, the killing of S. aureus was similar, whether engulfed in vivo or in
      vitro. However, S. aureus was less susceptible to phagocytosis and killing in
      vitro than P. mirabilis or E. coli, and the killing of S. aureus during in-vitro
      incubation of neutrophils that had engulfed the organism with in the abscess was
      similar to that of the gram-negative bacteria engulfed within the
      abscess.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1990145
TI  - Biotypes, antibiotic resistance and plasmids coding for CFA/I and STa in
      enterotoxigenic Escherichia coli strains of serotype O153:H45 isolated in Spain.
AB  - Enterotoxigenic Escherichia coli (ETEC) strains of serotype O153:H45 have been
      found recently to be a frequent cause of sporadic cases and outbreaks of neonatal
      diarrhoea in Spain and the most important cause of infant diarrhoea in Chile.
      Relationships between sugar fermentation patterns, resistance to antibiotics and
      plasmid profiles were analysed in nine E. coli O153:H45 strains isolated in Spain
      that synthesised CFA/I antigen and STa enterotoxin. Derivative strains obtained
      by curing with acridine orange, and transconjugants rendered antibiotic
      resistant, were characterised phenotypically and analysed for plasmid content.
      Two fermentation patterns were recognised: rhamnose fermenters (four strains) and
      rhamnose non-fermenters (five strains). The ability to ferment rhamnose was the
      only differential characteristic found among 49 carbohydrate fermentation tests
      used to establish fermentation patterns. All nine strains possessed similar
      plasmid profiles of three or four plasmids of 52-87 Mda. A non-conjugative large
      plasmid of 82 Mda or 87 Mda, depending upon the strain, was identified as that
      responsible for production of both CFA/I and STa. Resistance to antibiotics was
      determined by plasmids other than those coding for CFA/I and STa. Two conjugative
      resistance factors were identified: a 52-Mda plasmid coding for resistance to
      ampicillin, streptomycin and sulphonamide in rhamnose-fermenting strains, and a
      77-Mda plasmid coding for resistance to ampicillin, streptomycin, kanamycin,
      tetracycline and sulphonamide in rhamnose non-fermenting strains. Our results
      support the hypothesis that the prevalence and distribution of ETEC strains
      belonging to serotype O153:H45 in Spain and Chile could be due to the extensive
      cultural relations between Spain and South American from the past.

PMID- 1990147
TI  - [Continuous dynamic record of intracuff pressure in endotracheal intubated
      patients].
AB  - As static intracuff pressure record does not represent the pressure changes
      occurring during sputum suction, cough, and struggle, we have designed a PC
      polygraph to attempt a continuous dynamic monitoring. By means of a 93-7800 PC
      polygraph, we obtained 11 continuous dynamic records (129.2 +/- 44.2 min.,
      average) of intracuff pressures from 11 inhalation anesthetized patients and 8
      records (23.4 +/- 12.4 min., average) from 6 awake ventilatory assisted patients
      on whom the Hilo endotracheal tube was used. In anesthetized patients, the ratios
      of peak pressure (P) to base line pressure (P) labeled in 8 oral suction, 23
      endotracheal suction, and 11 struggles were 181.2 +/- 63.1%, 161.8 +/- 51.9% and
      162.0 +/- 53.9% respectively. The ratios of labeled complex average pressure (P)
      to base line pressure were 132.8 +/- 32.5%, 126.2 +/- 27.3% and 126.1 +/- 27.8%
      respectively. In awake ventilatory assisted patients, the ratios of P/P labeled
      in 15 oral suction, 45 endotracheal suction, 28 coughs, and 8 struggles were
      235.0 +/- 69.4%, 305.0 +/- 295.7%, 236.9 +/- 80.0%, and 174.7 +/- 65.0%
      respectively. The ratios of P/P were 131.9 +/- 55.9%, 139.5 +/- 50.1%, 156.9 +/-
      46.8%, and 122.1 +/- 36.5%. Reduction of endotracheal cuff pressure was noted
      immediately after removal of upper intrathoracic tumors measuring from 56.8 +/-
      7.6 mmHg to 41.9 +/- 6.4 mmHg in 3 patients. Time summation of the labeled events
      in five of our six ICU patients averaged less than 6% during the entire course of
      monitoring.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1990146
TI  - A cytotoxic haemolysin from Treponema hyodysenteriae--a probable virulence
      determinant in swine dysentery.
AB  - The haemolysin from a virulent strain of Treponema hyodysenteriae was extracted
      and injected into ligated loops of the ileum and colon of germ-free pigs. It
      caused severe epithelial damage, especially to the differentiated cells at the
      tips of the villi in the ileum and the cells in the intercrypt zones of the
      colon; goblet cells were less affected. The changes in the colon were similar to
      those seen in natural cases of swine dysentery. The ligated loop offers a means
      of investigating pathogenic mechanisms and the mode of action of the toxin. This
      study demonstrated that the haemolysin was a potent cytotoxin for pig
      enterocytes, and a probable virulence determinant in swine dysentery.

PMID- 1990148
TI  - [The action mechanism of the pineal gland in inhibiting sexual receptivity of
      female rats: (I). Is it concerned with the extrahypothalamic inhibitory
      pathway?].
AB  - Monosodium L-glutamate (MSG), as a neurotoxin, was administered subcutaneously at
      a dose of 4 mg/g body weight to rat pups on days 1 and 3 postnatally. The sexual
      receptivity expressed as lordosis quotient (LQ) in MSG-treated female rats (2.5
      months old) was significantly lower than that of the normal female ones, and this
      poor sexual receptivity of MSG-treated females could be improved by pinealectomy
      at the age of six weeks. In order to investigate the relationship between the
      inhibitory role of the pineal gland and the extrahypothalamic inhibitory pathway,
      normal control and MSG-treated rats were ovariectomized and implanted
      subcutaneously with estradiol capsule (20% estradiol benzoate, in 2mm silastic
      tube) at the age of 2.5 months. Three days after implantation, sexual receptivity
      was observed. Then, the anterior roof deafferentation (ARD) was preformed one
      week later and the sexual receptivity in both groups was compared again. The
      results showed that there was no significant difference of the lordosis response
      between the MSG-treated and the control groups before ARD, and the level of
      restoration by ARD in LQ of MSG-treated rats was similar to that of the control
      group. It seems that the extrahypothalamic inhibitory pathway of sexual
      receptivity may not be influenced by neonatal MSG-treatment. Our previous results
      indicated that the behavioral sensitivity to estradiol was altered by ARD.
      However, in the present study, the lordosis responses of MSG-treated and
      pinealectomized female rats were not significantly different from that of the
      control group after ovariectomy and exogenous estradiol implantation. This means
      that the behavioral sensitivities to estradiol were not changed by MSG-treatment
      or pinealectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1990149
TI  - Lactoferrin in rheumatoid arthritis and systemic lupus erythematous.
AB  - Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are prototypes
      of autoimmune diseases. In order to assess the inflammatory status in these
      conditions, lactoferrin, stored in specific granules of neutrophils, was measured
      in serum samples of patients with SLE and RA. In RA, the mean serum lactoferrin
      level (1221.397 +/- 289.476 ng/ml) was significantly higher than that in normal
      individuals (753.364 +/- 124.063 ng/ml). Surprisingly, there were no significant
      differences between active SLE (672.682 +/- 356.154 mg/ml) and inactive SLE
      (642.267 +/- 270.456 ng/ml). Still, no differences were found between normal
      volunteers, active SLE and inactive SLE. Serum lactoferrin in SLE correlated
      significantly with CRP (Rs = 0.4089, p less than 0.01), but not with complement
      level and ANA titers. Thus in RA serum lactoferrin was highly elevated and this
      indicated that PMN in systemic circulation was activated. In SLE the correlation
      of CRP with lactoferrin reflected the role of later protein in inflammation.

PMID- 1990150
TI  - [A preliminary study of family Apgar index in the Chinese].
AB  - The present study was designed to evaluate the clinical availability of family
      Apgar index in Chinese people. From August 1987 to February 1988, 113 samples
      from 45 Chinese families were collected from our record family patients. The
      family members who were over 12 years of age were asked to complete a family
      Apgar questionnaire and CHQ during a family visit. The patients age, sex, marital
      status, education, religion, family role, socioeconomic status were also
      recorded. The result showed that there was no significant correlation between the
      family Apgar scores and all of the patient's characteristics (sex, age, marital
      status, education, religion, family role, socioeconomic status) except the score
      of CHQ. It is suggested that the family Apgar index is a simple and useful
      instrument to screen out family dysfunctional patients in daily office practice.

PMID- 1990151
TI  - Management of penetrating abdominal injury.
AB  - We present the results of immediate exploratory laparotomies for penetrating
      abdominal injuries that were performed in the past five and half years. Thirty
      eight cases (37 males and 1 female) were collected in this study, ranging in age
      from 17 to 74 years, with a mean of 36 years. Nine suffered from gunshot injuries
      and 29 from stab injuries. The negative exploratory laparotomy rate was 22.2%,
      the surgical complication rate was 18.4%, and the mortality rate was 5%. In this
      retrospective study, we conclude that: 1. Patients with injuries of the abdomen
      or unstable vital signs should be operated on immediately. 2. Peritonitis signs
      are not absolute indications of the need for emergent exploration. 3. For the
      stab injury patients with stable pre-operative vital signs, conservative
      treatment with simple closure of wounds is adequate. Frequent checks of vital
      signs and abdominal condition can possibly prevent unnecessary operations.

PMID- 1990152
TI  - Intrathoracic extramedullary hematopoiesis simulating posterior mediastinal mass-
      report of a case in patient with beta-thalassemia intermedia.
AB  - Intrathoracic involvement of the extramedullary hematopoiesis is a rare
      condition. It is usually found in patients with thalassemia or hereditary
      spherocytosis. In the literature, only 79 cases have been reported. Here, in
      Taiwan, a 22 year-old female patient of beta-thalassemia intermedia presented
      with posterior mediastinal mass proved as an intrathoracic extramedullary
      hematopoiesis by thoracoscopic biopsy was reported.

PMID- 1990153
TI  - [Gastrectomy for advanced gastric carcinoma with serosal involvement].
AB  - Four hundred and eighty five gastric cancer patients underwent gastrectomy in the
      past 6 years and of those 332 patients (68.2%) were found to have only serosal
      involvement (se) or adjacent organ invasion (sei). Simple gastrectomy (SG) was
      carried out in 144 cases while radical gastrectomy (RG), which included systemic
      lymphadenectomy, was performed in 188 cases. This type of operation was chosen by
      the operators arbitrarily except in the presence of non-curative factors such as
      multiple liver metastasis, peritoneal seeding and distant metastasis, in which
      case SG was always used to relieve gastrointestinal obstruction or bleeding. The
      operative mortality of SG was 2.7% and that of RG was 3.2%. On average, 15.8
      lymph nodes were taken out per patient in SG and 33.6 lymph nodes in RG. The
      chance of nodal metastasis was higher in sei than in se. According to the
      Japanese General Rules of Gastric Cancer Study, we found that for gastric cancer
      with serosal involvement: (1) the long term result of RG was superior to SG in
      both stage 3 and 4 patients, (2) when absolute curative resection was achieved,
      the result was the best in stage 3 patients, (3) no patient in stage 4 who
      underwent absolute non-curative resection survived for more than 42 months,
      therefore this result was the worst. RG is recommended for advanced gastric
      cancer patients with serosal involvement whenever the patient's condition permits
      and in absence of the unresectable non-curative factors.

PMID- 1990154
TI  - Pathologic mechanisms of drug-induced lung disorders.
AB  - The pathology of drug-induced lung disease is approached on the basis of patterns
      of tissue reaction in this review. The entities described include various
      pathologic lesions, from diffuse alveolar damage to interstitial pneumonias and
      angiopathies. Because the histopathologic manifestations of drug injury are
      variable and nonspecific, pathogenetic mechanisms are emphasized. Drugs may cause
      injury by direct toxicity or by triggering immunologic responses, but often this
      neat distinction is blurred by the combined effects of preexisting lung injury
      and the concurrent administration of several drugs. Thus the identification of
      drug-induced lung disease requires thorough knowledge of the clinical history and
      rigorous analysis of histopathologic features.

PMID- 1990155
TI  - Lung disorders due to drug abuse.
AB  - Drug-related diseases of the lungs have been noted with increasing frequency in
      urban patients. These entities are also being seen in smaller urban and suburban
      settings, however. The spectrum of pathology is also changing coincident with the
      marked increase in crack cocaine use. The incidence of abnormal chest radiographs
      in cocaine users admitted with pulmonary complaints has ranged from 12% to 55%.
      Findings have included focal air space disease, atelectasis, pneumothorax,
      pneumomediastinum, and pulmonary edema. Pulmonary complications related to
      injections of illicit drugs have included pulmonary infection, pulmonary edema,
      particulate embolism, and talcosis. The "pocket shot" places the patient at risk
      for a unique set of complications. Radiologists should be aware of this wide
      spectrum of pulmonary disease that may be related to this increasingly frequent
      social problem.

PMID- 1990156
TI  - Drug-related pleural and mediastinal disorders.
AB  - The full range of mediastinal and pleural toxic effects of various drugs is
      reviewed. The importance of clinical information in suggesting the diagnosis of
      drug-induced disorders is emphasized. A separate section on the pleural and
      mediastinal toxic effects of illicit drugs is included.

PMID- 1990157
TI  - Radionuclide scanning in the detection of drug-induced lung disorders.
AB  - Drug-induced pulmonary toxicity commonly results in interstitial lung disease
      characterized by the presence of inflammatory cells in pulmonary parenchyma.
      Gallium-67 citrate lung scintigraphy is currently the most sensitive test for the
      detection of inflammatory lesions in the lungs. Although chest radiographs often
      detect interstitial lung disease, they may be normal during the early alveolitis
      stage, when gallium scans are positive. Therefore, gallium scans can be utilized
      for the early diagnosis of drug-induced pulmonary reactions, leading to
      withdrawal of the drug and preventing the irreversible and potentially serious
      complication of pulmonary insufficiency. Gallium scintigraphy can also be used to
      follow these patients because it reflects the inflammatory changes in the lungs.
      This article presents a survey of the literature on gallium-67 scintigraphy in
      drug-related pulmonary inflammation. Gallium scans have been reported as abnormal
      in pulmonary toxicity caused by amiodarone, busulfan, bleomycin, procarbazine,
      nitrofurantoin, pentazocine, cephalosporin, cyclophosphamide, and cocaine, even
      in the absence of radiographic findings. The role of gallium scintigraphy in the
      early detection of pulmonary toxicity is emphasized.

PMID- 1990159
TI  - Communications and communicating effectively.

PMID- 1990158
TI  - The clinical diagnosis of drug-induced pulmonary disorders.
AB  - An increasing number of drugs have been implicated in the pathogenesis of a broad
      spectrum of pulmonary diseases. The clinical and radiographic manifestations are
      often nonspecific, requiring a high index of suspicion by both the clinician and
      the radiologist. The review focuses on patterns of drug-induced pulmonary
      disease, including parenchymal disorders, pulmonary vascular disease, pleural
      processes, airway disease, mediastinal abnormalities, and neuromuscular
      disorders. In each category, the differential diagnosis, clinical assessment, and
      diagnostic evaluation are discussed.

PMID- 1990160
TI  - Prospective randomized multicenter comparison of in situ and reversed vein
      infrapopliteal bypasses.
AB  - We have performed a prospective, randomized, multicenter study to compare in situ
      and reversed vein grafts for long limb salvage bypasses from the proximal thigh
      to an infrapopliteal artery. Three hundred eighty-four patients required an
      infrapopliteal bypass for critical lower extremity ischemia. Of these, 259 were
      excluded because a short vein bypass was performed or because the vein was
      considered inadequate. The remaining 125 patients had a randomized vein bypass,
      63 reversed, 62 in situ. The two groups were similar with regard to risk factors,
      indications, graft dimensions, and outflow. Secondary patency at 30 months was
      similar for both techniques: reversed 67% +/- 9% (+/- SE); in situ 69% +/- 8%.
      For veins less than or equal to 3.0 mm in minimum distended diameter 24-month
      patency rates were 61% +/- 22% for 12 in situ veins and 37% +/- 29% for 10
      reversed veins (p greater than 0.05). Angiographic evaluation of failing grafts
      revealed lesions similar in type and frequency in both types of grafts. These
      included focal (in situ, n = 4; reversed, n = 7) and diffuse vein hyperplasia (in
      situ, n = 2; reversed, n = 1), and inflow and outflow stenoses (in situ, n = 4;
      reversed, n = 3). The incidence of wound complications and the mortality rate
      were similar for the two groups. These data show no significant difference in
      overall patency rates for the two types of vein grafts at 2 1/2 years.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1990161
TI  - Durability of vein graft revision: the outcome of secondary procedures.
AB  - Occlusive lesions that reduced graft blood flow and ankle systolic pressure were
      identified in 83 femorodistal saphenous vein bypasses by use of duplex scanning
      or arteriography. Sites of stenosis included vein conduit (n = 41), anastomoses
      (n = 20), outflow arteries (n = 15), or inflow (n = 9) arteries. One hundred
      three secondary procedures consisting of vein-patch angioplasty (n = 31),
      sequential (n = 21) or interposition (n = 17) graft placement, percutaneous
      transluminal balloon angioplasty (n = 17), or excision of the lesion and primary
      anastomosis (n = 16) were performed to correct primary (n = 85) or recurrent (n =
      18) graft stenoses. Cumulative graft patency after reintervention was 96% at 1
      year, and 85% at 5 years. Stenosis or occlusion of revision sites was less after
      excision (0 of 16) or replacement (1 of 17) of abnormal segments compared to vein
      patch angioplasty (8 of 31) or balloon angioplasty (9 of 18). Sequential or jump
      grafts constructed to improve graft outflow impaired by either myointimal or
      atherosclerotic occlusive lesions were the least durable secondary procedures.
      Five of eight graft failures in this series resulted from sequential/jump graft
      occlusion. All categories of secondary procedures normalized graft and limb
      hemodynamics, although only one third of patients reported symptoms of limb
      ischemia before revision. Surveillance of infrainguinal vein bypasses for
      occlusive lesions is a valid concept to salvage patent but hemodynamically
      failing grafts. Secondary procedures that excised the lesion, used autologous
      tissue reconstruction, and normalized hemodynamics at the revision site and in
      the vein bypass were associated with a low incidence of restenosis and prolonged
      graft patency.

PMID- 1990162
TI  - Simultaneous operative repair of multilevel lower extremity occlusive disease.
AB  - Sixty-two patients (39 men (63%), 23 women (27%), mean age 68 years) with
      multilevel lower extremity arterial occlusive disease underwent simultaneous
      inflow and outflow operative arterial repair consisting of aortofemoral bypass in
      22 (35%), axillofemoral bypass in 17 (28%), femorofemoral bypass in 15 (24%),
      iliac endarterectomy in 7 (11%), and unilateral aortoiliac bypass in 1 (2%),
      combined with 69 outflow procedures (unilateral in 55 patients, 89%), including
      above-knee femoropopliteal in 12 (17%), below-knee femoropopliteal in 35 (51%),
      femoroinfrapopliteal in 20 (29%), popliteal tibial in 1 (1%), and femoropedal
      bypass in 1 (1%). Multiple criteria were used to identify patients with
      multilevel disease likely to benefit from multilevel procedures. The operations
      were performed by two operating teams in a median time of 240 minutes. Prosthetic
      grafts were used for eight (13%) distal bypasses, the remainder were autogenous
      vein. There was one operative death (1.8%). The mortality rate, morbidity rate,
      and operative time were not significantly different from a group of patients who
      underwent concurrent, isolated inflow operations (aortofemoral, axillobifemoral,
      femorofemoral bypass or iliac endarterectomy). Mean follow-up was 14.9 months
      (range, 0 to 120). The life-table primary patency for the inflow procedures was
      92.6% at 24 months, the outflow was 94.9% at 24 months. Cumulative limb salvage
      was 90.9% at 48-month follow-up. All patients with claudication were relieved of
      their symptoms. We conclude that complete correction of multilevel disease can be
      accomplished with operative time, morbidity rate, and patency equal to that of
      single level repair. Multilevel procedures provide complete relief of symptoms in
      a higher percentage of patients than has been reported after single level repair.

PMID- 1990163
TI  - Laser angioplasty in peripheral vascular disease: symptomatic versus hemodynamic
      results.
AB  - Most early reports on the efficacy of laser angioplasty have used subjective
      symptoms rather than objective hemodynamic parameters to evaluate clinical
      results. We reviewed our experience with hot tip laser-assisted balloon
      angioplasty in 99 occluded or stenotic arterial segments during 80 procedures in
      71 patients, ranging from the aortic bifurcation to the tibial-peroneal trunk.
      Initial failure to successfully recanalize occluded or stenotic segments occurred
      in 13 instances (16%). Forty-one procedure-related complications occurred in 31
      patients (39%). Functional results were evaluated by use of life-table methods on
      the basis of symptomatic versus hemodynamic improvement. Cumulative patency rates
      for symptomatic and hemodynamic improvement were 91% and 64% at 1 month, 71% and
      48% at 6 months, and 57% and 34% at 1 year, respectively. These data suggest that
      symptomatic improvement alone gives a misleadingly high estimate of the efficacy
      of laser angioplasty when compared with more objective hemodynamic criteria (p
      less than 0.005). Hemodynamic success was more likely in aortoiliac lesions than
      femoropopliteal lesions (58% vs 18% at 1 year, p less than 0.01). Hemodynamic
      parameters should be used to evaluate the success of laser angioplasty, which in
      its present form, is associated with frequent complications and poor long-term
      success.

PMID- 1990164
TI  - Abdominal aortic aneurysm with perianeurysmal fibrosis: experience from 11
      Swedish vascular centers.
AB  - Case records of 2026 patients operated on because of abdominal aortic aneurysms
      from 11 Swedish Vascular Centers were reviewed and revealed 98 cases (4.8%) of
      inflammatory abdominal aortic aneurysm. Also included in this case-control study
      was an analysis of a randomized group of 82 patients from the same centers who
      had noninflammatory abdominal aortic aneurysms. Four inflammatory aneurysms were
      ruptured, compared with 16 in the noninflammatory group (p less than 0.01). A
      higher proportion of patients with inflammatory abdominal aortic aneurysms had
      symptoms that led to radiographic investigations. The median erythrocyte
      sedimentation rate was 39 mm versus 19 mm (26% of patients with inflammatory
      abdominal aortic aneurysms had erythrocyte sedimentation rates greater than 50
      mm; p less than 0.001), and the serum creatinine level was increased in 27 and 8
      patients (p less than 0.01) in the inflammatory and noninflammatory groups,
      respectively. Preoperative investigations revealed ureteral obstruction in 19
      patients with inflammatory abdominal aortic aneurysms, of whom 12 had
      preoperative nephrostomy or ureteral catheter placement. At operation, 20
      additional patients exhibited fibrosis around one or both ureters. Although
      ureterolysis was performed in 19 patients, preoperative and postoperative
      creatinine levels did not differ between these patients and the conservatively
      treated ones. Duration of surgery (215 vs 218 minutes), intraoperative blood loss
      (2085 vs 2400 ml) and complications did not differ significantly between the
      groups. Overall operative (30-day) mortality was equal (11% vs 12%) but was
      increased for patients undergoing elective surgery for inflammatory abdominal
      aortic aneurysms (9% vs 0%; p = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1990165
TI  - Ruptured abdominal aortic aneurysm: the Harborview experience.
AB  - During the last decade (1980 to 1989) 186 patients with ruptured abdominal aortic
      aneurysm were admitted to a single urban hospital. Ninety-six percent of these
      patients had a prehospital systolic blood pressure less than 90 mm Hg. Management
      included paramedic field resuscitation and transport, an emergency department
      diagnostic protocol completed in an average of 12 minutes, rapid transport to a
      dedicated emergency operating room, aneurysmorrhaphy by general surgery chief
      residents under the supervision of specialist vascular surgeons, and skilled
      postoperative intensive care unit care. Nevertheless, 130 (70%) patients died in
      the first 30 postoperative days--3% in the emergency department, 13% in the
      operating room, 51% in the intensive care unit, and 3% on the ward or at home.
      Certain features--age greater than 80 years, female gender, persistent
      preoperative hypotension despite aggressive crystalloid and blood replacement,
      admission hematocrit less than 25, transfusion requirements exceeding 15 units-
      were associated with a greater than 90% likelihood of death. No patient with
      preoperative cardiac arrest survived more than 24 hours. From this experience we
      conclude that, although "optimal" prehospital, emergency department, operating
      room, and postoperative care can improve the outcome of patients with ruptured
      abdominal aortic aneurysms in shock, most such patients will die. Certain
      clinical features predict such excessive mortality rates after ruptured abdominal
      aortic aneurysms that withholding operation may be reasonable. Screening of
      patients at high risk for abdominal aortic aneurysm, followed by elective
      aneurysmorrhaphy, is clearly indicated.

PMID- 1990166
TI  - Probability of rupture of an abdominal aortic aneurysm after an unrelated
      operative procedure: a prospective study.
AB  - It has been assumed by some authors that patients with abdominal aortic aneurysms
      may be at increased risk of rupture after unrelated operations. From July 1986 to
      December 1989, 33 patients (29 men, 4 women) with a known abdominal aortic
      aneurysm underwent 45 operations. Twenty-eight patients had an infrarenal
      abdominal aortic aneurysm, and five patients had a thoracoabdominal aneurysm. The
      abdominal aortic aneurysm ranged in transverse diameter from 3.0 to 8.5 cm
      (average 5.6 cm). Twenty-seven patients underwent a single operation, and six
      patients had two or more (range of 1 to 6). Operations performed were abdominal
      (13); cardiothoracic (9); head/neck (2); other vascular (11); urologic (7);
      amputation (2); breast (1). General anesthesia was used in 29 procedures,
      spinal/epidural in 6, and regional/local in 10. One postoperative death occurred
      from cardiopulmonary failure. One patient died of a ruptured abdominal aortic
      aneurysm at 20 days after coronary artery bypass (1/33 patients [3%]; 1/45
      operations [2%]). Fourteen patients had repair of their abdominal aortic aneurysm
      at a later date, an average of 18 weeks after operation. Four patients had
      abdominal aortic aneurysm considered too small to warrant resection (average 3.6
      cm). Four patients were considered at excessive risk for elective repair. The
      five thoracoabdominal aneurysm were not repaired. Four patients are awaiting
      repair. During this same 40-month period, two other patients, not known to have
      an abdominal aortic aneurysm, died of a ruptured abdominal aortic aneurysm after
      another operative procedure, at 21 days and 77 days. All three ruptured abdominal
      aortic aneurysms were 5.0 cm or greater in transverse diameter.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1990167
TI  - Aortocaval and iliac arteriovenous fistulas: recognition and treatment.
AB  - Despite the well characterized physiologic effects of aortocaval or iliac
      arteriovenous fistulas, patients with such uncommon lesions may manifest a
      diverse array of symptoms, and diagnosis is often delayed or overlooked. To
      examine clinical features that facilitate recognition and allow successful
      repair, a 30-year experience with 20 such fistulas was reviewed. Fourteen
      fistulas were caused by aneurysm erosion, four followed iatrogenic injury during
      lumbar disk surgery, and two developed from abdominal gunshot wounds. The
      interval from presumed occurrence to diagnosis ranged from 3 hours to 8 years.
      The diagnosis was not recognized before surgery in five (25%) patients. Back pain
      (70%) was the most common symptom. The presence of a typical abdominal bruit
      (80%) was the most reliable physical finding, but its significance was
      occasionally overlooked or misinterpreted. Congestive heart failure was prominent
      in only seven (35%) patients. Severe lower extremity edema and mottling was the
      primary manifestation in eight cases, often causing initial confusion with venous
      thrombosis. Hematuria (5 patients) and oliguric renal failure (4 patients), both
      fully reversible after fistula repair, also caused diagnostic uncertainty. The
      mean preoperative cardiac output was 12.2 L/min, falling to 5.4 L/min with
      fistula repair. Mean blood loss was 5960 ml, supporting use of intraoperative
      autotransfusion. Two operative deaths (10%) occurred, both in patients not
      correctly diagnosed before surgery. Despite varied modes of presentation, prompt
      recognition and use of appropriate operative techniques should achieve successful
      repair.

PMID- 1990168
TI  - Intravascular ultrasonography: validation studies and preliminary intraoperative
      observations.
AB  - Intravascular ultrasonography is emerging as an important imaging modality to
      assess the presence, distribution, and extent of atherosclerotic vascular
      disease. To determine the accuracy and clinical utility of intravascular
      ultrasonography, a flexible catheter-based system was used to generate two
      dimensional, cross-sectional vascular images. In 23 arteries of 11 sheep 206 in
      vivo images demonstrated an echo-free lumen surrounded by three distinct
      concentric acoustic transitions corresponding to intima, media, and adventitia.
      Ultrasound measurements of lumen diameter and area correlated significantly with
      those of corresponding arteriographic measurements obtained by use of digital
      calipers (r = 0.91, r = 0.86). To evaluate clinical feasibility, intraoperative
      images (n = 160) were obtained in 10 patients undergoing vascular bypass or
      hemodialysis access procedures. The images depicted luminal configuration and
      arterial wall morphologic characteristics. Measurements of lumen diameter and
      lumen area correlated closely with corresponding intraoperative arteriography (r
      = 0.81, r = 0.79). The ultrasound images demonstrated arterial stenoses, intimal
      hyperplasia, intraluminal thrombus, polytetrafluoroethylene graft material, and
      anastomotic sites. We conclude that flexible catheter-based ultrasonography
      produces images that accurately demonstrate arterial wall architecture, lumen
      diameter, and area. Intraoperative application can produce images that provide
      unique information thus expanding the clinical potential of ultrasonography as a
      guidance system for vascular procedures.

PMID- 1990169
TI  - Use of duplex imaging to assess suitability of the internal mammary artery for
      coronary artery surgery.
AB  - The internal mammary artery is the preferred conduit for coronary artery surgery.
      To determine the role, if any, of preoperative duplex imaging in assessing the
      suitability of this vessel, preoperative noninvasive measurements of internal
      mammary artery diameter and blood flow were performed in 243 patients. The left
      internal mammary artery was insonated through the third intercostal space by use
      of duplex scanner (5.0 MHz probe) before coronary artery surgery. Internal
      mammary artery diameter (millimeters), peak systolic velocity
      (centimeters/second), and mean velocity (centimeters/second) were measured, and
      internal mammary artery flow was calculated from velocity and cross-sectional
      area. In 45 of these patients the internal mammary artery diameter also was
      measured during surgery with a sterile caliper, and blood was collected for 30
      seconds from the transected internal mammary artery to measure flow. These
      findings were compared to the preoperative values. In 243 patients the mean
      internal mammary artery diameter was 2.34 +/- 0.03 mm, and mean peak systolic
      blood flow was 226.7 +/- 6.3 ml/min. In the 45 patients in whom intraoperative
      measurements were obtained, preoperative mean internal mammary artery diameter
      was 2.39 +/- 0.05 mm and was not significantly different from the intraoperative
      mean internal mammary artery diameter of 2.36 +/- 0.04 mm. Preoperative peak
      systolic flow was 231.3 +/- 8.1 ml/min, and mean flow was 110.3 +/- 7.1 ml/min;
      intraoperative flow measured 136 +/- 3.6 ml/min. Noninvasive determinations
      correlated with operative findings for internal mammary artery diameter (r =
      0.87) (p less than 0.05), peak systolic blood flow (r = 0.70) (p less than 0.05),
      and mean blood flow (r = 0.60) (p less than 0.05).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1990170
TI  - The accuracy of CT scanning in the diagnosis of abdominal and thoracoabdominal
      aortic aneurysms.
AB  - As CT scanning has evolved as a reliable clinical tool, the use of angiography in
      the diagnosis of aortic aneurysmal disease has diminished. Fewer than 25% of
      patients with aortic aneurysmal disease undergo aortic angiographic evaluation at
      our institution. A prospective clinical study was undertaken to assess the
      validity of this policy. One hundred patients with clinical or ultrasonographic
      evidence of aortic aneurysms were evaluated prospectively during the period July
      1987 to December 1989. All patients underwent CT scanning as an initial
      evaluation. Patients were selected for angiography if they fulfilled any of the
      following criteria: radiographic evidence of thoracoabdominal or juxtarenal
      aneurysms, or horseshoe kidney; or clinical suggestion of renal artery stenosis,
      mesenteric arterial insufficiency, aortoiliac occlusive disease, or lower
      extremity aneurysmal disease. During this period 19 patients (19%) underwent both
      CT scanning and angiography. The indications for angiography were
      thoracoabdominal aneurysms (7), juxtarenal aneurysms (2), clinical evidence of
      mesenteric insufficiency (1) or renal insufficiency (2), evidence of lower
      extremity aneurysmal disease (3), or severe aortoiliac occlusive disease (4).
      Eighty-one patients (81%) underwent CT scanning as the only radiographic
      evaluation. No patient was adversely affected by elimination of angiographic
      evaluation. CT scanning revealed inflammatory aneurysms (4), retroaortic renal
      veins (2), and horseshoe kidney (1). This study suggests that most (81%) patients
      with aortic aneurysmal disease can be adequately evaluated by CT scanning, and
      that a very selective policy of angiographic evaluation is indicated.

PMID- 1990171
TI  - Magnetic resonance imaging: a reliable test for the evaluation of proximal
      atherosclerotic renal arterial stenosis.
AB  - Symptomatic renal artery stenosis is a significant and treatable clinical
      problem. A reliable and accurate noninvasive method of screening for renal artery
      stenosis has not yet been found. We used magnetic resonance imaging to study 37
      patients who had undergone recent renal angiography. Fourteen patients had normal
      renal arteries by angiography. In 23 patients either unilateral or bilateral
      stenosis or occlusion was present. The disease process in all patients appeared
      to be atherosclerosis. The average age of the 37 patients was 68 years. The
      magnetic resonance scans and angiograms were read independently by two different
      radiologists, each of whom was blinded to the clinical history and the results of
      the other study. Renal arterial stenoses found on angiogram and magnetic
      resonance scans were graded as absent (0% to 24%), mild (25% to 49%), moderate
      (50% to 74%), or severe (75% to 99%). The magnetic resonance imaging results
      concurred with the angiographic findings in 70 of 77 arteries (91%). Magnetic
      resonance imaging predicted the presence of a greater than 50% stenosis of the
      renal artery with a sensitivity of 100% and a specificity of 94%. Magnetic
      resonance imaging may prove to be the best noninvasive screening test for
      proximal atherosclerotic renal arterial stenosis.

PMID- 1990172
TI  - Technique and clinical results of carotid stump back-pressure to determine
      selective shunting during carotid endarterectomy.
AB  - A method of confirming carotid back pressure accuracy, variability during carotid
      clamping, and the clinical results with a modified back pressure shunt criterion
      were evaluated in 665 carotid endarterectomies. Mean arterial pressure, back
      pressure, and internal jugular vein pressure were measured. Cerebral perfusion
      pressure (back pressure-jugular vein pressure) and the collateral to hemisphere
      vascular resistance ratio, (ratio = [arterial pressure-back pressure]/[back
      pressure-jugular vein pressure]) were calculated. A shunt was used when cerebral
      perfusion pressure less than 18 mm Hg. Back pressure accuracy was confirmed by
      test occlusion of the internal carotid artery distal to the plaque. Initial back
      pressure values were falsely high in 83 (12.5%) carotid endarterectomies. The
      mean SD (n = 665, mm Hg) were arterial pressure = 84.0 +/- 9.06, back pressure =
      41.0 +/- 15.9, jugular vein pressure = 6.2 +/- 3.9, cerebral perfusion pressure =
      35.1 +/- 5.7, and resistance ratio = 1.85 +/- 1.44. Perfusion pressure was less
      than 18 mm Hg in 82 (12.3%), of which 74 (11.1%) were shunted, and 8 (1.2%) had
      perfusion pressure increased greater than or equal to 18 mm Hg during carotid
      endarterectomy with phenylephrine. Back pressure was less than 25 mm Hg in 107
      (16.1%), less than or equal to 25 in 114 (17.1%), and less than 50 mm Hg in 481
      (72.3%). Pressures were continuously monitored during 28 carotid
      endarterectomies, and all had a positive linear relationship between arterial
      pressure and back pressure, and minimal variability in the back pressure/arterial
      pressure and resistance ratios. Only two patients (0.3%) had a new neurologic
      deficit in the first 12 hours after carotid endarterectomy.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1990173
TI  - A prospective study of the incidence and natural history of femoral vascular
      complications after percutaneous transluminal coronary angioplasty.
AB  - Over a 14-month period patients undergoing 144 percutaneous transluminal coronary
      angioplasty procedures were evaluated for the presence of complications at the
      femoral puncture site. After percutaneous transluminal coronary angioplasty each
      patient was examined by a surgeon, and then a color-flow duplex scan of the groin
      was obtained. On the initial scan eight pseudoaneurysms, three arteriovenous
      fistulas, one combined arteriovenous fistula-pseudoaneurysm, and one thrombosed
      superficial femoral artery were detected for a major vascular complication rate
      of 9%. Pseudoaneurysm formation was associated with the use of heparin after
      removal of the arterial sheath. Seven pseudoaneurysms (initial extravascular
      cavity size range 1.3 to 3.5 cm) were followed with weekly duplex scans, and all
      thrombosed spontaneously within 4 weeks of detection. The three patients with
      isolated arteriovenous fistulas were each followed for at least 8 weeks, and the
      arteriovenous fistulas persisted. Early surgical intervention for
      postcatheterization femoral pseudoaneurysms is usually unnecessary as thrombosis
      often occurs spontaneously. We would advocate an operative approach for
      pseudoaneurysms that are symptomatic, expanding, or associated with large
      hematomas. Iatrogenic femoral arteriovenous fistulas should be considered for
      elective repair, but this may be delayed for several weeks without adverse
      sequelae.

PMID- 1990174
TI  - Mechanisms of vein graft atherosclerosis: LDL metabolism and endothelial actin
      reorganization.
AB  - We have explored the effect of arterial hemodynamics on endothelial cell
      morphology and low-density lipoprotein metabolism in human saphenous vein
      segments harvested from tissue donors. An arterial pulsatile perfusion system was
      used to impose physiologic pressures and flows for 20 hours on saphenous vein and
      companion (control) femoral artery segments. A venous perfusion apparatus was
      also employed for the perfusion of a second (control) saphenous vein segment for
      the same period of time. Calculations of fluid shearing and wall tensile stresses
      were performed and related to induced changes in endothelial cell geometry and
      cytoskeletal actin organization and the incorporation, degradation, and
      localization of intact low-density lipoprotein within the vessel wall. Our
      results indicate that, compared with native arteries and veins, a 20-hour
      exposure of test saphenous veins to arterial hemodynamics induced (1) a
      significant increase in endothelial cell luminal surface area and perimeter
      independent of alignment with flow, (2) disassembly of the dense peripheral band
      of actin with a concomitant assembly of stress fibers, and (3) a two- to fourfold
      elevation in the undegraded low-density lipoprotein content, localized primarily
      within the subendothelial intima. Although the exact mechanisms underlying these
      results are uncertain, the focal accumulation of intramural low-density
      lipoprotein may be related to the loss of normal barrier function during
      endothelial cell enlargement, which is accompanied by transient cytoskeletal
      reorganization during the adaptation to arterial flow.

PMID- 1990175
TI  - Ruptured abdominal aortic aneurysm.

PMID- 1990176
TI  - The value of computed tomography in the management of symptomatic abdominal
      aortic aneurysms.

PMID- 1990177
TI  - Postischemic cell membrane dysfunction.

PMID- 1990178
TI  - Medical efforts intensify in Desert Storm's fourth week.

PMID- 1990179
TI  - Defense appears to have advantage over offense presently in biological warfare.

PMID- 1990180
TI  - Flight surgeon, corpsman among first casualties.

PMID- 1990181
TI  - VA Hospitals prepare for Desert Storm casualties.

PMID- 1990182
TI  - Concerns grow about allied prisoners of war.

PMID- 1990183
TI  - Often thwarted treaty efforts leave chemical, biological weapons a still potent
      threat.

PMID- 1990184
TI  - From the National Institutes of Health.

PMID- 1990185
TI  - From the Centers for Disease Control. Seasonality in sudden infant death
      syndrome.

PMID- 1990186
TI  - Van Gogh: Meniere's disease? Epilepsy? Psychosis?

PMID- 1990187
TI  - Reading disability in children.

PMID- 1990188
TI  - Preconception care of diabetes. Glycemic control prevents congenital anomalies.
AB  - To test the value of intensive management of diabetes before and during early
      pregnancy, 84 women recruited prior to conception were compared with 110 women
      who were already pregnant referred at 6 to 30 weeks' gestation. All underwent
      daily measurement of fasting and postprandial capillary blood glucose levels.
      Mean blood glucose levels during embryogenesis and organogenesis were within 3.3
      to 7.8 mmol/L in 50% of preconception subjects and exceeded 10 mmol/L in 6.5%.
      One major congenital anomaly occurred in 84 infants (1.2%) of women treated
      before conception compared with 12 anomalies in 110 infants (10.9%) of mothers in
      the postconception group. Transient symptomatic hypoglycemia occurred during
      embryogenesis in 60% of women in the preconception group, with a median frequency
      of 2.7 episodes per week, but was not associated with excess malformations. We
      conclude that education and intensive management for glycemic control of diabetic
      women before and during early pregnancy will prevent excess rates of congenital
      anomalies in their infants.

PMID- 1990189
TI  - Maternal outcome after open fetal surgery. A review of the first 17 human cases.
AB  - A few fetal diseases may benefit from surgical treatment before birth, but
      hysterotomy and subsequent delivery by cesarean section pose a risk to the
      otherwise unaffected mother. To assess maternal risk of mortality, morbidity, and
      reproductive potential after fetal surgery, we reviewed our experience with 17
      highly selected women who underwent fetal surgery. Fifteen of these procedures
      were performed for one of two congenital anomalies: severe bilateral
      hydronephrosis and congenital diaphragmatic hernia. There were no deaths or
      serious maternal injuries. In the 14 women who continued pregnancy after
      hysterotomy, uterine irritability and preterm labor were frequent complications,
      requiring early confinement in most cases. There has been no detectable effect on
      future fertility, as indicated by eight subsequent normal pregnancies. We
      conclude that hysterotomy for fetal surgery can be accomplished without unduly
      endangering the mother's life or her future reproductive potential. However,
      morbidity related to premature labor remains a serious problem, and our ability
      to control uterine contractions after hysterotomy remains the limiting factor in
      human fetal surgery.

PMID- 1990190
TI  - Panic attacks in the community. Social morbidity and health care utilization.
AB  - This article focuses on social morbidity and health care utilization in persons
      with panic attacks not meeting full diagnostic criteria for panic disorder. The
      findings are based on data from a random sample of over 18,000 adults drawn from
      five US communities. Panic attacks not meeting full criteria for panic disorder
      have a relatively high lifetime prevalence (3.6% of the adult population).
      Persons with panic attacks had impairment in perceived physical and emotional
      health, and in occupational and financial functioning, increased use of health
      care facilities, emergency departments, and psychoactive drugs. Persons with
      panic attacks were intermediate in severity between those with panic disorder and
      those with other psychiatric disorders. The findings could not be explained by
      comorbidity with other psychiatric disorders. We conclude that panic attacks have
      clinical significance and are associated with substantial morbidity.

PMID- 1990191
TI  - Prolonged continuous acyclovir treatment of normal adults with frequently
      recurring genital herpes simplex virus infection. The Acyclovir Study Group.
AB  - In this 3-year study of suppressive acyclovir for recurrent genital herpes,
      patients with more than six recurrences per year were randomized initially to 400
      mg of acyclovir or placebo orally two times per day, with recurrences treated
      with 200 mg of acyclovir five times per day for 5 days. In the second year of the
      study, all patients received acyclovir as a daily suppressive or intermittent
      acute therapy; in the third year, all received daily acyclovir. Among 525
      patients completing 3 study years, 289 received 3 years of suppressive therapy
      and 236 received 1 year of acute therapy followed by 2 years of suppressive
      therapy. Of those who completed the third year, 61% were recurrence free that
      year; 25% of the suppressive therapy-only group were recurrence free for all 3
      years. The annual recurrence rate dropped from more than 12 recurrences per year
      at baseline to 1.0 (suppressive therapy) and 1.4 (acute and suppressive therapy)
      recurrences during the third year. No significant toxic effects were detected.
      Daily suppressive acyclovir therapy was effective and well tolerated.

PMID- 1990192
TI  - Periodic physician recredentialing.
AB  - The quality of health care services is a major concern of consumers and commands
      attention in the national health policy debate. The government and business
      emphasize quality medical care for its immediate relevance to cost containment.
      Federal legislation has been introduced requiring physician recertification, 19
      of 23 specialty boards are requiring periodic recertification, and it has been
      proposed that reimbursement for physician services be contingent on compliance
      with standards of medical care. In the past 3 years, planning has been in
      progress in New York State to implement periodic physician recredentialing for
      medical relicensure. The current plan emphasizes peer review of guidelines
      developed by specialty societies and proposes educational enhancement, not loss
      of license, if a need to correct deficiencies is identified.

PMID- 1990193
TI  - A new look at typhoid vaccination. Information for the practicing physician.
AB  - Most cases of typhoid fever in the United States occur in international
      travelers, with the greatest risk associated with travel to Peru, India,
      Pakistan, and Chile. Laboratory workers and household contacts of long-term
      carriers are also at greater risk than the general population. Decisions to the
      use typhoid vaccine involve weighing the risk of illness against the risk of
      vaccine reactions. Until recently, the only typhoid vaccine commercially
      available to US civilians was a heat-phenol-inactivated parenteral product that
      is 51% to 77% effective in preventing typhoid fever but frequently produces local
      pain and swelling, fever, headache, and malaise. A new orally administered, live
      attenuated vaccine, made from the Ty21a strain of Salmonella typhi, has been
      recently licensed in the United States. This vaccine provides equivalent
      protection with a much lower incidence of adverse reactions. It is administered
      in a four-dose series given over 7 days. Since neither vaccine offers total
      protection, the most important elements in prevention of typhoid fever remain
      sound biosafety precautions in laboratory workers and care in selecting food and
      beverages by those traveling to areas where typhoid fever is endemic.

PMID- 1990194
TI  - Cocaine metabolite detection in homicide victims.
AB  - We analyzed the blood of homicide victims for the presence of cocaine's major
      metabolite, benzoylecgonine. During 1989 in Fulton County, Georgia, 81% of 275
      homicide victims were tested for benzoylecgonine; 40% tested positive. The
      proportions of blacks and victims of firearm injuries who tested positive for
      benzoylecgonine were significantly larger than the respective proportions for
      whites and victims of injuries not involving firearms. The data show overall
      proportions of benzoylecgonine positivity much larger than those previously
      reported in the literature. The relationships between homicide, race, firearms,
      and cocaine use deserve further study.

PMID- 1990195
TI  - Educating physicians in home health care. Council on Scientific Affairs and
      Council on Medical Education [corrected].
AB  - A growing proportion of health care, especially long-term care, should best and
      most appropriately be provided in the home setting. Physicians have largely
      remained on the periphery of this reemerging area of health care. Yet if home
      health care is to reach its full potential, physicians must fulfill their
      essential role as members of the home health team. Direct physician input and
      participation are needed to ensure that home health care is safe and medically
      appropriate. Physician involvement will enhance the supervision of medical care
      in the home, and physicians' expertise is also much needed for home health care
      quality assurance and clinical research. Role models and training experiences
      must be developed for new physicians so that they can integrate home health care
      skills and values into their future practices. Although most of the usual
      physician objections to home health care involvement can be addressed by
      education, the problem of inadequate reimbursement is substantive and must be
      addressed by policy change.

PMID- 1990196
TI  - Recredentialing.

PMID- 1990197
TI  - A piece of my mind. Accomplices.

PMID- 1990198
TI  - HIV/AIDS: is it gone yet?

PMID- 1990199
TI  - Guide to lobbying.

PMID- 1990200
TI  - AIDS prevention education in Topeka public schools.

PMID- 1990201
TI  - The Kansas AIDS education and training center.

PMID- 1990202
TI  - HIV/AIDS and nursing care.

PMID- 1990203
TI  - The clinical nurse specialist in HIV care.

PMID- 1990204
TI  - Endothelin peptides: a possible role in glomerular inflammation.

PMID- 1990205
TI  - Dual parameter flow cytometry for deoxyribonucleic acid and intermediate filament
      proteins of residual mature teratoma. All tumor cells are aneuploid.
AB  - Most testicular germ cell tumors of adults are presumably derived from polyploid
      carcinoma in situ. Thus, one would expect that even highly differentiated
      teratoma components are aneuploid and that it is unlikely to find diploid tumor
      cell (sub)populations. We studied 10 residual mature teratomas (RMTs) using a
      dual parameter flow cytometry procedure. Nuclear DNA was stained with propidium
      iodide and cytoplasmic intermediate filament proteins, in particular,
      cytokeratins, with fluorescein isothiocyanate-labeled specific monoclonal
      antibodies. Cells in RMTs, immunoreactive with antibodies to cytokeratins were
      considered to be tumor cells. These were always found to be aneuploid, in
      agreement with the available cytogenetic data on these tumors. The diploid cells
      present in RMTs were devoid of cytokeratins; therefore, these cells represent the
      nonmalignant normal host stromal and inflammatory cells. These results, in
      accordance with our earlier finding, indicate that diploid testicular germ cell
      tumors are extremely rare in adults, and that even the histologically benign
      somatic tissues in RMT after polychemotherapy are aneuploid.

PMID- 1990206
TI  - Glomerular tumor necrosis factor and interleukin 1 during acute aminonucleoside
      nephrosis. An immunohistochemical study.
AB  - Acute aminonucleoside nephrosis progresses to glomerulosclerosis. The mechanisms
      for this phenomenon are not entirely known. Our objectives were to identify
      macrophage (m phi)-derived peptide growth factors (i.e., tumor necrosis factor
      and interleukin 1), using immunohistochemical means, in glomeruli of rats with
      acute aminonucleoside nephrosis. Recently, a role for glomerular m phi s has been
      suggested as one of the possible mechanisms responsible for this transition from
      acute glomerular injury to glomerulosclerosis. Since peptide growth factors are
      elaborated by m phi s and produce alterations in mesangial cell proliferation and
      protein biosynthesis, we investigated whether these cytokines were present in
      glomeruli during aminonucleoside nephrosis, which has been typically regarded as
      a nonimmune toxic glomerulopathy. Fourteen days after puromycin aminonucleoside
      (PA) delivery, nephrotic control rats (PA/control) and nephrotic animals that had
      been maintained on an essential fatty acid-deficient (EFAD) diet (PA/EFAD) for 8
      weeks before PA, manifested cytoplasmic tumor necrosis factor and interleukin 1
      within cells located in the glomerular mesangium as detected by
      immunohistochemical means. Despite equivalent levels of albuminuria and fasting
      total cholesterol during peak nephrosis, the PA/EFAD rats had significant
      reductions in the number of tumor necrosis factor-positive glomerular cells (1.8
      +/- 0.1 versus 8.5 +/- 0.4, p less than .001) and interleukin 1-positive
      glomerular cells (1.5 +/- 0.1 versus 7.2 +/- 0.5, p less than .001) in comparison
      with the PA/control group. These data correlated with a reduction in the number
      of ED-1-positive cells (i.e. glomerular m phi s) in glomeruli of PA/EFAD animals
      as compared with PA/control rats (2.2 +/- 0.3 versus 10.9 +/- 1.4, p less than
      .001), suggesting that m phi-derived peptide growth factors may be important
      determinants in initiating a pathobiologic sequence culminating in
      glomerulosclerosis in this model.

PMID- 1990207
TI  - Characterization and differential distribution of the three major human protein
      kinase C isozymes (PKC alpha, PKC beta, and PKC gamma) of the central nervous
      system in normal and Alzheimer's disease brains.
AB  - Brain kinases may play important roles in normal memory as well as in the
      pathogenesis of neurodegenerative diseases. However, there is scant information
      on these enzymes in the human brain. For this reason, we characterized the
      immunohistochemical localization of protein kinase C (PKC) isozymes in human
      Alzheimer's disease (AD) and non-AD control brains. Using monoclonal antibodies
      to PKC alpha, PKC beta, and PKC gamma isozymes, we (a) determined the
      distribution of each PKC isozyme in eight different brain regions (cerebellum,
      hippocampus, as well as midfrontal, orbital frontal, motor, occipital, parietal,
      and temporal cortices) from AD and non-AD control brains and found that these
      patterns were generally similar to those in the rat brain; (b) showed that there
      were no significant differences in the normal staining intensity of the
      monoclonal antibodies in AD and non-AD control brain regions except in the
      hippocampus; (c) observed striking PKC immunoreactivity in globular and linear
      profiles in the periphery (corona) of AD senile plaques; and (d) demonstrated
      that PKC alpha immunoreactivity was enhanced in reactive astrocytes associated
      with senile plaques and other lesions (embolic infarcts) in both AD and non-AD
      control brains. The data on the normal distribution of each PKC isozyme were
      corroborated in quantitative studies of PKC alpha, PKC beta, and PKC gamma
      protein levels in human postmortem brain regions by Western blotting using our
      antibodies. We conclude that these three major PKC isozymes can be analyzed
      directly in postmortem human brain, which is an important first step in
      understanding the potential role that abnormal phosphorylation might play in the
      pathogenesis of AD.

PMID- 1990208
TI  - Involvement of the immune system in human atherogenesis: current knowledge and
      unanswered questions.

PMID- 1990209
TI  - Differential effects of myocarditic variants of Coxsackievirus B3 in inbred mice.
      A pathologic characterization of heart tissue damage.
AB  - The histopathologic features reflecting the influence of virus genotype and host
      differences on myocarditis were evaluated in six inbred mouse strains (C57BL/6,
      B10.D2, BALB/c, DBA/2, A/J, and C3H/HeJ) inoculated with four respective variants
      of coxsackievirus B3 (CVB3-CG, -SH, -ST, or -NR). The most severe and most
      prevalent histologic lesions occurred after infection with CVB3-SH or -CG
      variants, regardless of mouse strain. In general, C57BL/6 mice showed the lowest
      susceptibility to myocarditis while A/J or C3H/HeJ animals had the highest
      susceptibility, whether early (7 days) or late (21 days) after CVB3 inoculation.
      Lesion size and calcification depended to an extent on disease severity, but
      calcification in the C3H/HeJ myocardium was notably sparse. Lesions clustered
      distinctly in the midthird of the ventricular wall in some animals, particularly
      in DBA/2 mice. Extensive pericarditis occurred exclusively in BALB/c and DBA/2
      animals and predominated over the right ventricle anterolaterally. Virus titer in
      the heart did not account for disease susceptibility among mouse strains. These
      characteristics reflect differences in pathogenicity and are important
      considerations in the study of mechanisms in CVB3-induced myocarditis in mice.

PMID- 1990210
TI  - Monoclonal antibody GB3 defines a widespread defect of several basement membranes
      and a keratinocyte dysfunction in patients with lethal junctional epidermolysis
      bullosa.
AB  - An antigen expressed at the dermal-epidermal junction as well as in some other
      human basement membranes (BM) has been detected by the use of a monoclonal
      antibody termed GB3. This antigen, synthesized by cultured normal human
      keratinocytes, has been identified as a 600-kilodalton glycoprotein different
      from other known components of BM. Using indirect immunofluorescence, GB3 was
      found to be not reactive with the epidermal BM in patients with lethal junctional
      epidermolysis bullosa. The present study demonstrates (by indirect
      immunofluorescence) that GB3 defines a widespread defect of several BM in these
      patients. Furthermore, it gives evidences for an intrinsic biologic defect of
      lethal junctional epidermolysis bullosa epidermal keratinocytes using in vitro
      culture of these cells. Whether the lack of GB3 reactivity is the consequence of
      a true absence of the antigen or an alteration of its molecular structure is not
      yet known. Nevertheless, GB3 is a useful probe for both rapid and prenatal
      diagnosis of lethal junctional epidermolysis bullosa, which will give new
      insights into the molecular comprehension of this disorder.

PMID- 1990211
TI  - Eosinophil granulocyte proliferation and differentiation in schistosomal
      granulomas are controlled by two cytokines.
AB  - In parasitic diseases, eosinophilia is controlled at the systemic level by
      soluble, circulating factors. In addition to their medullar production and
      migration to tissues involved by parasitosis, eosinophil populations in
      inflammatory infiltrates may be locally amplified by their in situ proliferation.
      In granulomas induced in liver tissue by eggs of schistosome worms, eosinophil
      proliferation and differentiation are observed. We have shown that they were
      under control of two cytokines, the activity of which can be demonstrated in
      supernatants of isolated granulomas maintained in culture for 24 hours. One of
      them has been identified as interleukin-5. The other one is secreted by adherent
      cells obtained from periovular granulomas, among which macrophages represent more
      than 99% of cells. It is considered to correspond to the previously described
      factor, secreted by inflammatory macrophages mobilized on intraperitoneal glass
      implants in mice with chronic schistosomiasis. In acute schistosomiasis, the
      activity of the interleukin-5 was predominant, whereas in the chronic phase of
      the disease, the stimulation of peripheral eosinopoiesis is taken over by the
      factor secreted by adherent cells. During the progression from the acute to the
      chronic phase of schistosomiasis, the immune reactivity of the host is down
      regulated by T suppressor lymphocyte circuits. In addition, a redistribution of
      cellular controls of the host reaction to parasites may act as a complementary
      mechanism for establishment of the viable equilibrium between host and parasite.

PMID- 1990213
TI  - Elevated intracranial pressure stimulates gastric contractility in the rat.
AB  - The gastric contractile response to elevated intracranial pressure (ICP) was
      studied in conscious rats. Elevation of intracranial pressure to 20 mm Hg was
      associated with a marked increase in the amplitude of gastric contractions (70
      90% over baseline) without any change in contractile frequency (5.2 +/- .5
      contractions per min). The increase in contractility continued for 45 min
      following release of the pressure. Vagotomy completely blocked the increase in
      gastric contractility seen with elevation in ICP. We conclude that acute
      elevation of intracranial pressure in rats results in increased force of gastric
      contractions. The forceful contractions persist despite release of the pressure
      and the increased contractile force is vagally mediated.

PMID- 1990212
TI  - Enhancement of re-epithelialization with topical zinc oxide in porcine partial
      thickness wounds.
AB  - We investigated the effect of locally applied zinc on the healing of partial
      thickness skin wounds in the domestic pig using two zinc compounds (zinc oxide
      and zinc sulfate) in two different vehicles (a gauze compress and a collagen
      sponge). The rate of re-epithelialization was determined morphometrically 48 and
      64 hr after infliction of standardized square wounds (4.8 cm2 and 400-microns
      deep) with an electrokeratome. Zinc oxide in gauze significantly (P less than
      0.05) increased re-epithelialization of the wounds (33% more epithelialized than
      control wounds after 64 hr) and in collagen sponge (76% more epithelialized than
      control wounds after 64 hr). Zinc sulfate had no such stimulatory effect at any
      dosage or vehicle used. Our results show that topical zinc oxide enhances re
      epithelialization of partial-thickness wounds in nutritionally balanced pigs and
      that the mode of delivery of zinc is probably critical for achieving the
      beneficial healing effect of zinc.

PMID- 1990214
TI  - Platelet-activating factor in porcine Pseudomonas acute lung injury.
AB  - We investigated the role of platelet-activating factor (PAF) in acute septic lung
      injury by examining the effects of the selective PAF antagonist SRI 63-675 and by
      measuring PAF in lung tissue in the porcine model. Four groups of pigs (15-25 kg)
      were studied: saline control (C, n = 5); Pseudomonas (Ps, n = 9), given 5 x 10(8)
      CFU/ml at 0.3 ml/20 kg/min intravenously over 1 hr; SRI (n = 3), given SRI 63-675
      in a 40 mg/kg bolus; and SRI + Ps (n = 5). Ps infusion produced a fulminant lung
      injury characterized by a threefold increase in pulmonary arterial pressure at 30
      min and persistent pulmonary hypertension (P less than 0.05 vs C), a significant
      (P less than 0.05 vs C) decrease in arterial oxygen tension (PaO2) from 60 min, a
      significant (P less than 0.05 vs C) increase in extravascular lung water (EVLW)
      from 120 min, and a significant (P less than 0.05 vs C) increase in albumin flux
      determined scintigraphically as slope index at 150-180 min. Systemic arterial
      pressure and cardiac index (CI) decreased significantly (P less than 0.05) in the
      Ps group vs C at 60 and 180 min, respectively. Bolus injection of SRI 63-675 at
      the time of Ps infusion blocked the early pulmonary hypertension, attenuated the
      early and late fall in PaO2, ameliorated the increase in EVLW, and prevented the
      late (150-180 min) increase in albumin flux. SRI 63-675 had minimal effects on Ps
      induced hypotension or alterations in CI.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1990215
TI  - Prostacyclin and prostanoid modifiers aid ischemic skin flap survival.
AB  - Prostacyclin, the stable prostacyclin analogue carbacyclin, the thromboxane
      synthetase inhibitor UK-38,485, and the phosphodiesterase inhibitor dipyridamole
      were tested on rabbit epigastric free flaps for their ability to improve flap
      survival after a period of ischemia. Control flaps infused with a balanced salt
      solution had a 39.9% survival, whereas prostacyclin, carbacyclin, and
      dipyridamole significantly increased flap survival to 68.4% (P less than 0.05),
      66.4% (P less than 0.05), and 66.9% (P less than 0.05), respectively. UK-38,485
      improved survival slightly to 47.6% although not significantly. The improved flap
      survival correlated with the vasodilatory properties of the three successful
      agents whereas the antithrombotic properties of UK-38,485 were not sufficient, on
      their own, to increase flap survival.

PMID- 1990216
TI  - Pharmacokinetics and toxicity of isolated perfusion of lung with doxorubicin.
AB  - The treatment of pulmonary metastases from soft tissue sarcomas with chemotherapy
      has an overall response rate of less than 30%, and the majority of these
      responses are short lived. It is postulated that increased drug delivery to the
      pulmonary metastases may improve the outcome of these patients. An isolated
      perfusion system would have the ability of delivering increased levels of drug to
      target tissue without the systemic toxic effect of the drug. The purpose of this
      study was to establish the pharmacokinetics of doxorubicin delivery, lung
      toxicity, and the ideal dose for clinical application in an in vivo isolated
      perfusion model. Our results suggest that normothermic isolated perfusion of the
      lung with doxorubicin using a dose level up to 6 micrograms/ml in the perfusate
      can be accomplished without histologic lung injury, systemic toxicity, or adverse
      clinical outcome. Perfusate concentration of greater than 7 micrograms/ml caused
      significant histologic injury and adverse clinical outcome without systemic
      toxicity. The technique may be utilized in selective settings to improve
      treatment in mesenchymal tumors metastatic to the lung.

PMID- 1990217
TI  - Short-term in vitro drug testing of mamma tumors: relation to estrogen and
      progesterone receptor levels, age, and proliferation rate.
AB  - The correlation between age, proliferation rate of tumors, estrogen and
      progesterone receptors, and in vitro chemosensitivity to Adriamycin was studied
      on 43 primary mamma tumors. From an univariate statistical analysis of the
      results, it appeared that sensitive tumors, unlike resistant tumors, have fewer
      estrogen receptors and show a higher proliferation rate. And in addition, they
      are blocked to a greater extent by Adriamycin. In both groups age and
      progesterone receptors were not significantly different. A multivariate
      statistical analysis showed that in the classification into sensitive and
      resistant tumors, the percentage remaining incorporation after addition of
      Adriamycin and the proliferation rate contributed 94 and 5%, respectively. The
      first variable was the best measure for in vitro chemosensitivity. The
      classification of the tumors with the aid of a discriminant function proved to be
      successful in 91% of all the cases. No significant difference was observed
      between the in vitro sensitivity to Adriamycin when patients were divided into
      two groups according to age (less than or equal to 50 and greater than 50 years;
      64 and 45% sensitive, respectively). This indicates that all patients benefit
      from the treatment. It also appeared that 85% of the estrogen negative tumors
      were sensitive to Adriamycin. So a chemotherapeutic instead of a hormonal therapy
      has to be considered for all ages, particularly in the case of estrogen negative
      receptors.

PMID- 1990218
TI  - Evaluation of initial hepatic allograft function with changes of free plasma
      amino acids in canine orthotopic liver transplantation.
AB  - We investigated the correlation between amino acid level and hepatic graft
      function. Plasma amino acid levels were measured at three time periods during
      canine orthotopic liver transplantation. During the anhepatic phase, plasma amino
      acid levels rose except for tryptophan. Cystine and alanine (Ala) increased
      significantly to 210 +/- 28% (n = 20, mean +/- SEM) and 203 +/- 11% from
      preoperative values (100%), respectively. In animals successfully surviving
      without hepatic insufficiency after transplantation of fresh livers (n = 7),
      plasma amino acid levels were restored to preoperative values within 3 hr
      following reperfusion. On the other hand, in animals that died from hepatic
      insufficiency within 5 days after grafting of warm ischemically damaged livers (n
      = 8), plasma amino acids, especially Ala, phenylalanine, total free plasma amino
      acids, and aromatic amino acids progressively increased to 216 +/- 25, 274 +/-
      36, 152 +/- 15, and 152 +/- 15% at 3 hr after reperfusion. These were
      significantly higher compared to those of the group of animals transplanted with
      fresh livers (P less than 0.01-0.05). Furthermore, higher values were found in
      those dogs transplanted with warm ischemically damaged livers surviving for
      shorter periods. Also in dogs that died from hepatic insufficiency within 8 hr
      after grafting of livers preserved for 24 hr (n = 5), amino acid levels were at
      high values at 3 hr. These results suggest that in animals having good graft
      function, plasma amino acid levels are restored to preoperative values by 3 hr
      after reperfusion. In other cases, primary nonfunction should be strongly
      suspected after liver transplantation.

PMID- 1990219
TI  - Intermittent hepatic arterial or portal occlusion reduces liver tumor growth.
AB  - The effect of repeated, intermittent hepatic vascular occlusion on liver tumor
      growth was studied in 32 rats. An adenocarcinoma was inoculated in the left liver
      lobe. After 8 days, the tumor size was measured and then, in three groups, the
      hepatic artery was occluded intermittently during 5 days for 15 min, 1 hr, or 2
      hr daily, respectively. The tumor growth after 6 days in these groups was
      compared with that in a group where instead the portal vein was occluded
      intermittently during 5 days for 15 min, and with that in a group of sham
      operated control rats. In the control rats, the tumor volume (mean +/- SEM)
      increased from 0.16 +/- 0.03 to 1.34 +/- 0.15 cm3 during the 6 days of
      experiment. It was found that repeated, intermittent occlusion of the hepatic
      artery or the portal vein, retarded the liver tumor growth to 30-60% of the
      growth rate in sham-operated controls (P less than or equal to 0.015). The 15-min
      daily hepatic artery or portal vein occlusion was found to reduce the tumor
      growth rate as much as daily hepatic artery occlusion for 2 hr. It is suggested
      that short, daily, intermittent hepatic vascular occlusions might be efficient in
      the palliative treatment of liver malignancy.

PMID- 1990220
TI  - The role of fibrinogen in mediating staphylococcal adherence to fibers.
AB  - The use of tampons and surgical gauze pads and colonization with Staphylococcus
      aureus have been established as risk factors for the development of toxic shock
      syndrome. To elucidate the role of blood factors in the mediation of
      staphylococcal adherence to fibers used in tampons and surgical packing, an
      adherence assay with cotton fibers was developed. Results demonstrated that
      cotton disks precoated with fibrinogen in the presence of human serum albumin
      bound a significant percentage of the inoculum for both staphylococcal strains
      tested when compared to human serum albumin controls. Likewise, fibers pretreated
      with plasma or defibrinated blood containing a small amount of fibrin revealed
      comparable staphylococcal adherence to that of fibrinogen. In contrast, fibers
      pretreated with serum, fibronectin, or vitronectin did not exhibit significant
      augmentation in staphylococcal attachment in comparison to human serum albumin
      controls. The attachment of staphylococci to fibrinogen and/or fibrin appeared to
      be specific and is blocked by goat anti-human fibrinogen antibody, but not
      fibronectin, vitronectin, or nonimmune goat IgG. Thus, our data indicate that
      fibrinogen/fibrin is the dominant blood component in the mediation of
      staphylococcal adherence to fibers used in tampons and surgical gauze pads.

PMID- 1990221
TI  - Identification of tissue sites for increased albumin degradation in sarcoma
      bearing mice.
AB  - Plasma albumin concentration declines in both experimental and clinical cancer.
      Previous investigations have demonstrated that this is partly explained by
      increased breakdown of albumin. The present study has identified the tissue sites
      for increased albumin degradation in a nonmetastasizing sarcoma mouse (C57/BL6J)
      model. Results have been compared to nontumor-bearing animals either freely fed
      or food restricted (pair-weighed) so that their body composition was similar to
      tumor-bearing animals. Tumor-bearing mice had increased albumin degradation (0.13
      +/- 0.02 mg/hr/g bw) compared to both freely fed (0.09 +/- 0.007) and pair
      weighed control animals (0.05 +/- 0.008). Radioactivity from circulating
      [3H]raffine aldehyde labeled albumin appeared with maximum peak values in
      lysosomes isolated from both tumor and nontumor tissues at 48 hr following iv
      injection. The intralysosomal accumulation of radioactivity was two- to threefold
      higher in tumor tissue compared to liver tissue, although the specific activity
      of protease(s) for albumin degradation measured in vitro was not higher in tumor
      tissue (30.4 +/- 3.6 mg/hr/g tissue) compared to normal liver tissue (36.9 +/-
      1.7). Accounting for the entire tumor the proteolytic capacity for albumin
      breakdown was however much larger in the tumor (161.6 +/- 32.6 mg/organ) compared
      to both normal liver (37.5 +/- 2.3) and tumor-host liver (56.4 +/- 2.8).
      Pepstatin inhibited 78 +/- 6% of the proteolytic activity in the tumor measured
      by 125I-labeled undenatured mouse albumin as the substrate. Leupeptin inhibited
      49 +/- 6%. There was a significantly decreased breakdown of albumin in both
      skeletal muscles and the gastrointestinal tract from tumor-bearing
      animals.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1990222
TI  - Crystalloid resuscitation restores but does not maintain cardiac output following
      severe hemorrhage.
AB  - Although Ringer's lactate (RL) is routinely used for resuscitation, it is not
      known whether this fluid alone restores and maintains the depressed cardiac
      output (CO) following severe hemorrhage. To study this, a fiberoptic catheter was
      inserted to the level of the aortic arch in rats. Following indocyanine green
      (0.05 mg) administration, CO was measured using an in vivo hemoreflectometer
      (IVH). The rats were then bled to and maintained at a mean arterial pressure
      (MAP) of 40 mmHg until 40% of the shed blood volume was returned in the form of
      RL. They were resuscitated with 2, 3, or 4 times (X) the volume of the shed blood
      with RL and CO recorded at various intervals thereafter. The results indicate
      that CO decreased significantly during hemorrhage and remained depressed
      following resuscitation with 2 or 3X RL. CO was normal immediately after
      resuscitation with 4X RL, but it was not sustained and decreased significantly
      0.5 to 8 hr postresuscitation. This was not due to the decreased hematocrit since
      acute hemodilution did not decrease CO. These results indicate that: (1) the
      progressive changes in CO following hemorrhage and resuscitation can be measured
      in rats by using IVH; (2) resuscitation with 4X RL restores total peripheral
      resistance to normal, but does not maintain CO, suggesting that pharmacological
      support may be needed under such conditions; (3) the lack of maintenance of CO
      following resuscitation may play an important role in the development of multiple
      organ failure after severe hemorrhage.

PMID- 1990223
TI  - Outcome following femur fracture and subsequent cecal ligation and puncture in
      endotoxin-sensitive (C3H/HeN) and endotoxin-resistant (C3H/HeJ) mice.
AB  - This study examined the effect of sepsis following trauma in a reproducible model
      of sepsis--cecal ligation and puncture (CLP)--in endotoxin-sensitive (C3H/HeN)
      and endotoxin-resistant (CeH/HeJ) mice. Studies used CLP with a 25-gauge needle
      at different time intervals following injury, as induced by femur fracture (FF),
      to determine the effects of sublethal sepsis on survival after trauma. There was
      a 3% mortality for FF alone in both groups. Mortality in C3H/HeJ mice was not
      significantly increased over FF alone except when CLP followed FF by 3 days (45%,
      P less than 0.02, Chi-square). In contrast, C3H/HeN mice had significantly
      increased mortality rates (75 to 90%, P less than 0.001) versus FF alone at all
      intervals between FF and CLP. Mortality for FF plus CLP was significantly greater
      for C3H/HeN compared to C3H/HeJ (P less than 0.001) for all time intervals
      between FF and CLP. In conclusion, animals exposed to a septic episode following
      FF had significantly greater mortality than FF animals without a septic
      challenge. Endotoxin-sensitive mice had significantly higher mortality after CLP
      and significantly increased mortality when CLP followed FF (regardless of timing)
      compared to endotoxin-resistant mice.

PMID- 1990224
TI  - Antibacterial effects of fibrin glue-antibiotic mixtures.
AB  - In the present in vitro study, we investigated the duration of action and
      antibacterial effects of nonautologous fibrin glue (FG) combined with antibiotics
      (Abs) including Ciprofloxacin, Teicoplanin, Cefoxitin, and Gentamicin; the effect
      of FG alone on bacterial growth was also evaluated. The rate of Ab diffusion from
      combined FG-Ab clots was evaluated by separate elution with pooled human serum
      (HS) and normal saline (NS); supernatants were removed daily and assayed for
      active concentrations of each Ab. The effects of FG and combined FG-Ab clots on
      bacterial growth were evaluated by inoculating brain-heart infusion (BHI) with
      Staphylococcus aureus, followed by the addition of FG or FG-Ab clots; a separate
      set of studies was also performed with the addition of mouse lung homogenate
      (MLH) as well. The addition of Ab to FG clots resulted in continuous diffusion of
      the Ab into the surrounding HS or NS for up to 5 to 7 days; however, more than
      two-thirds of the Ab diffused out within 2 to 3 days regardless of the Ab used.
      The antibacterial effects of FG-Ciprofloxacin and FG-Teicoplanin clots were
      significant compared to those of FG clots not containing Ab. In addition, the
      presence of FG clots (in BHI) resulted in a reduction in bacterial growth
      compared to that of BHI alone. The addition of MLH to BHI resulted in increased
      bacterial growth, but this effect was inhibited by the presence of combined FG-Ab
      clots.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1990225
TI  - Significance of the endothelial lining in prevention of intimal thickening of
      autogenous vein grafts in dogs.
AB  - To better comprehend the role of the endothelial lining in occurrence and
      development of intimal thickening in arterially implanted autogenous vein grafts,
      two models of canine femoral arteries were prepared. In the Group I model, the
      implanted autogenous vein graft was kept under a normal flow condition for 2 to 4
      weeks after implantation, then was exposed to an abnormal flow (poor run-off). In
      case of a 3- to 4-week normal flow, intimal thickening was practically nil.
      Scanning electron microscopic studies showed that this 3- to 4-week period
      corresponded to that of re-endothelialization of the autogenous vein grafts.
      Immunohistochemical studies of fibrinogen distribution in the autogenous vein
      graft wall in the Group II model revealed that the permeation of fibrinogen was
      enhanced in case of an abnormal flow condition for about 2 weeks after the
      implantation. We interpret these observations to mean that intimal thickening was
      induced by an accelerated permeability in the presence of abnormal flow
      conditions until full re-endothelialization after the implantation.

PMID- 1990227
TI  - A histometric analysis of skeletal myofibers following 90 min of tourniquet
      ischemia and reperfusion.
AB  - Routine tourniquet use causes sublethal hypoxic cellular injury and results in
      edema formation. Using a histochemical morphometric technique, edema caused by 90
      min of tourniquet-induced ischemia and 3 hr of reperfusion is measured in the
      different muscle fibers of a primate model. The degree of cellular swelling is
      shown to be related to the fiber's metabolic dependence upon oxygen. After
      reperfusion, predominantly oxidative type 1 fibers show a 29% increase in
      diameter, P less than 0.0005, type 2a fibers which are both oxidative and
      glycolytic increase by 7%, P less than 0.005, and the glycolytic type 2b fibers
      increase by 5%, P less than 0.01. A 48% increase in interfiber distance occurs
      with reperfusion, P less than 0.01. By quantifying the different fibers'
      responses to ischemic injury, this method may be of use in investigating the
      pathophysiology and prevention of reperfusion injury and the post-tourniquet
      syndrome.

PMID- 1990226
TI  - Development of lung metastases after curative intraperitoneal chemotherapy in a
      rat colon cancer model.
AB  - A model of colon peritoneal carcinomatosis was developed by injecting 5 x 10(7)
      viable tumor cells intraperitoneally into Fisher 344 rats. All 40 control rats
      developed bulky abdominal tumor with ascites and died of peritoneal
      carcinomatosis and bowel obstruction (median survival 5 weeks). One day after
      tumor implantation, treatment group rats received a single intraperitoneal
      injection of single agent or combination chemotherapy. The most active
      intraperitoneal single agents were 5-fluorouracil, cisplatin, and etoposide. The
      most active combination was 5-fluorouracil and cisplatin. Combination
      chemotherapy produced a significant increase in median, 10-week, and 20-week
      survival (vs control and single agent). Six of 11 (55%) rats treated with
      intraperitoneal combination chemotherapy dying between 10-20 weeks died of lung
      metastasis with cure of intraperitoneal tumor. The increased ability of
      intraperitoneal combination chemotherapy to cure intraperitoneal disease was
      offset by the development of lung metastasis.

PMID- 1990228
TI  - Oleic acid induced pancreatitis in pigs.
AB  - An experimental model of edematous pancreatitis in pigs was established and
      measurement of pancreatic macro- and microcirculatory parameters and
      determinations of pancreatic enzymes (lipase, phospholipase A) and vasoactive
      mediators (prostanoids, kallikrein, kininogen) were performed. During general
      anesthesia the pancreas was isolated in situ. Pancreatic microcirculatory
      parameters were measured using videofluorescence microscopy after iv
      administration of FITC-Dextran. In hourly collected samples lipase and
      phospholipase A activities were determined enzymatically, concentrations of
      kallikrein, kininogen, and selected prostanoids were measured by
      radioimmunoassay. Two experimental groups were studied: (1) control (n = 9); (2)
      edematous pancreatitis induced by injection of oleic acid into the pancreatic
      artery (free fatty acid, ffa; n = 10). The animals were followed up for 6 hr.
      Systemic hemodynamic parameters remained constant in both groups. In the
      pancreatitis group pancreatic blood flow and O2-consumption decreased
      significantly (-55 and -49%), while pancreatic vascular resistance increased
      significantly (+50%). During baseline conditions 41% of all capillaries were
      perfused. In the pancreatitis group there were both areas with persistent stasis
      as well as areas with continuous perfusion. However, in the latter areas the
      portion of perfused capillaries decreased significantly to 27%. In the control
      group the portion of perfused capillaries remained constant. Liberation of lipase
      and phospholipase A especially into lymph and ascites fluid was measured during
      pancreatitis. Furthermore, considerable releases of kallikrein into lymph (+50%)
      and ascites (+800%) and a marked consumption of kininogen in lymph (+90%) and in
      ascites fluid (+80%) were measured. Activation of the arachidonic acid cascade
      and a significant release of prostacyclin and thromboxane A2 into pancreatic
      venous blood and lymph was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1990229
TI  - Peptides of human immunodeficiency virus (HIV) evoke rat colonic electrolyte
      secretion inhibitable by the somatostatin analog octreotide.
AB  - An integral transmembrane glycoprotein of the Human Immunodeficiency Virus (HIV)
      is gp 41. Five peptides (P1, P2, P3, P4, and P5) containing a conserved region of
      the gp 41 molecule have been synthesized. We tested P3, P4 and P5 for their
      effects on short-circuit current (Isc) across rat colonic mucosa. All three
      peptides increased the Isc; P5 was the most potent agonist. Serosal pretreatment
      of tissues with the chloride transport inhibitor, bumetanide (0.1 mM) or chloride
      replacement with gluconate, inhibited the response, suggesting that the increase
      in Isc was due to stimulation of active chloride secretion. The synthetic
      somatostatin analog octreotide (0.1 mM) also inhibited (P less than .05) the
      response to P5 (1 microM). The data provide a possible rationale for one aspect
      of the efficacy of octreotide in treating secretory diarrhea in patients with
      Acquired Immunodeficiency Syndrome (AIDS).

PMID- 1990230
TI  - The biological significance of malondialdehyde determination in the assessment of
      tissue oxidative stress.
AB  - Although lipid peroxidation of biological samples may be assessed by different
      chemical and physical methods, those based on the measurement of malondialdehyde
      formed from the breakdown of endoperoxides during the last stages of the
      oxidation of a polyunsaturated fatty acid, appear as the most widely used. Among
      the various methods to evaluate malondialdehyde, which include direct
      spectrophotometry or high pressure liquid chromatography, the reaction with
      thiobarbituric acid to form a colored adduct appears as a more rapid, inexpensive
      and sensitive technique. This method, however, is subject to some interferences
      which, if not considered, may lead to erroneous results. The present review
      emphasizes the significance of malondialdehyde measurement in biological samples,
      the chemical conditions of its reaction with thiobarbituric acid and the
      different procedures to isolate and determine the malondialdehyde-thiobarbituric
      acid adduct.

PMID- 1990231
TI  - A rapid screening test for HIV-1 antibodies: application to biological studies on
      human tissue.
AB  - Human umbilical cord vessels are commonly used as a source of human vascular
      tissue for physiological studies and as a source of endothelial and smooth muscle
      cells. Blood samples from 236 umbilical cords were tested for the presence of HIV
      1 antibodies to access the prevalence of HIV-1 infection and to evaluate possible
      methods for screening umbilical cords. Ten of the 236 samples were HIV-1 antibody
      positive by ELISA whereas 3 were positive by Western blot and a new method, the
      Quick-Western blot. Two of the 3 positive samples contained antibody bands
      against gp160, gp120, gp41, and p24 HIV-1 proteins, and one sample had antibodies
      against only gp160, gp120 and gp41. The Quick-Western blot required only 45
      minutes for the analysis while the ELISA and Western blot took 3 hours and 18
      hours, respectively. These data indicate that HIV-1 infection in mothers may
      present a hazard to researchers using human umbilical cords as a source of
      vascular tissue. The Quick-Western blot method is a simple, portable, rapid and
      accurate method that may be used to screen blood. The short analysis time of the
      Quick-Western blot allows the identification of infected blood before the tissue
      deteriorates as a source of cells or vascular tissue for experimental studies.

PMID- 1990232
TI  - Detection of secreted and temporarily inducible heat shock responsive proteins in
      mouse testicular tissue.
AB  - Temperature-induced effects on the synthesis of murine testicular proteins were
      investigated by one- and two-dimensional SDS polyacrylamide gel electrophoresis.
      Newly synthesized proteins were monitored by incorporation of 35S-methionine and
      autoradiography. Three heat shock responsive proteins, which are differently
      affected by elevated temperatures, are described. These proteins represent
      special examples for how testicular cells respond to environmental stress. One of
      these proteins, HSl36, is synthesized and secreted at 38 degrees C, whereas at
      lower, scrotal temperatures it is not detectable. HSlD74 protein is synthesized
      at elevated temperatures, but only in prepuberal testis, not in adult. Synthesis
      of the third example, HSR28, is decreased within the seminiferous tubules, but
      only in those regions which bear cell associations of the elongation stage. These
      results indicate that the use of DNA probes of the 'heat shock'-gene family might
      not be sufficient to describe the molecular reasons for impaired spermatogenesis
      following hyperthermia.

PMID- 1990233
TI  - Interactions between sialoadenectomy and capsaicin-sensitive afferent fibers on
      gastric acid secretion in rats.
AB  - In this study we have investigated the relative influence of capsaicin-sensitive
      afferents and sialoadenectomy on gastric acid secretion. Sialoadenectomized
      (SALX) rats showed a decrease in gastric acid secretion and an increase in
      gastric calcitonin gene-related peptide-like immunoreactivity (CGRP-li) as
      compared to sham-operated animals. Capsaicin pretreatment (50 + 100 mg kg-1 in
      two days) markedly decreased gastric CGRP-li in both sham and SALX-operated rats
      and increased acid concentration and output only in SALX animals. In this latter
      case the concomitant absence of two potent endogenous antisecretory agents (CGRP
      and epidermal growth factor; EGF) may contribute to the observed hypersecretion.
      Gastric content of vasoactive intestinal polypeptide (VIP)-li was unaffected in
      SALX and capsaicin-treated rats. Capsaicin-sensitive afferents and EGF contained
      in the salivary glands may interact in the regulation of the gastric acid
      secretion.

PMID- 1990235
TI  - Biotransformation of 4-androstene-3,17-dione by green cell suspension of
      Marchantia polymorpha: stereoselective reduction at carbon 17.
AB  - The biotransformation of 4-androstene-3,17-dione by a green cell suspension of
      Marchantia polymorpha was studied. It was found that the cultured cells
      stereoselectively reduce the carbonyl group of 4-androstene-3,17-dione from the
      re-face at C-17 to form testosterone as the primary metabolite.

PMID- 1990234
TI  - Depletion of rat liver glucocorticoid receptor hormone-binding and its mRNA in
      sepsis.
AB  - Glucocorticoid receptor (GR) hormone-binding activity, its physical
      characteristics, and GR mRNA levels were studied in the liver, brain and muscle
      of normal (saline-injected) and hypermetabolic septic rats 24 h after the
      subcutaneous injections of E. coli. The GR levels (hormone-binding activity)
      declined by about 40%, 56%, and 40% in septic liver, brain, and muscle cytosol,
      respectively. The mechanism of the decrease in the GR levels in sepsis was
      studied in liver. The GR levels remained low (45% of control hormone-binding)
      even after 48 h of E. coli administration. The decrease in the liver GR occurred
      in the 9S untransformed GR. The 9S GR from septic liver transformed to the 4S
      form in proportions comparable to the control liver GR. In addition, the 4S GR
      from control and septic liver was capable of binding to DNA-cellulose to a
      similar extent. The GR mRNA level in septic liver declined by about 30%. Thus, a
      decrease in GR hormone-binding activity in sepsis appears to be due to a decline
      in the steady-state GR mRNA level and not from a change in the qualitative
      properties of the GR protein.

PMID- 1990236
TI  - Further evidence for the hypothesis that beta-endorphin mediates maternal
      deprivation effects.
AB  - Lung DNA synthesis was examined in 9-day-old rat pups following a 2-hour
      separation from their mothers (maternal deprivation), and compared to that of
      pups placed with a nipple ligated dam (food deprivation) or a lactating dam
      (control). Maternally deprived pups consistently showed a significant reduction
      in lung DNA synthesis which was not attributable to food deprivation. Central
      administration of naloxone prevented the decrease in DNA synthesis observed after
      maternal deprivation but did not inhibit the reductions in lung DNA synthesis
      seen two hours after sc administration of isoproterenol, suggesting that DNA
      response to maternal deprivation is a specific opioid receptor mediated event.
      These results are consistent with previous reports from our laboratory indicating
      that CNS beta-endorphin may mediate many of the biological alterations observed
      following maternal deprivation in neonatal rats.

PMID- 1990237
TI  - Subcellular distribution of enkephalin precursor proteins in rat dental pulp and
      the usefulness as a substrate for enkephalin-producing enzymes.
AB  - The subcellular distribution of enkephalin (EK) precursor proteins was
      investigated to clarify the intracellular site of biosynthesis of EK in rat
      dental pulp tissue. The contents of met-EK-like peptides in nuclear, microsomal,
      and supernatant fractions of the pulp tissue were markedly increased after
      sequential digestion with trypsin and carboxypeptidase B, indicating the
      enrichment of the precursors in these fractions. Sephadex G-100 gel filtration
      showed a common peak of the precursor proteins in the homogenate and its
      microsomal and supernatant fractions, and the molecular weight was determined to
      be about 58,000 by SDS polyacrylamide gel electrophoresis. Both the partially
      purified precursor protein from the supernatant fraction and N alpha-benzoyl-DL
      arginine-beta-naphthylamide (BANA) were used as substrates for a lysosomal enzyme
      separated by Sephadex G-75 gel filtration. The major peak of EK-producing
      activity of the enzyme was identical with that of BANA-degrading activity of the
      enzyme. These results demonstrate the EK-producing activity of lysosomal
      proteinase, and also indicate the usefulness of the two substances as substrates
      for the enzyme.

PMID- 1990238
TI  - Pretreatment with drug-specific antibody reduces desipramine cardiotoxicity in
      rats.
AB  - The effect of a drug-specific antibody on desipramine (DMI) cardiotoxicity was
      studied in rats. Animals were pretreated i.v. with 4.2 g/kg of a monoclonal
      antibody (anti-TCA) followed by DMI HCl 30 mg/kg i.p. (molar ratio of anti-TCA
      binding sites to DMI = 0.56). Peak QRS complex prolongation was substantially
      lower after pretreatment with anti-TCA than after control antibody (70 +/- 14 v.
      21 +/- 4%, p less than 0.001). Time to peak toxicity was the same in both groups.
      Binding of DMI by anti-TCA was demonstrated by a higher serum total DMI
      concentration and increased DMI binding in serum after anti-TCA compared to
      controls. The DMI concentration in anti-TCA treated animals was lower in some
      organs (brain, lung, liver, spleen), but not in others (heart, muscle, kidney,
      fat). The calculated fraction of the DMI dose bound by anti-TCA was 19.9%. The
      steepness of the DMI dose-response curve was examined by administering DMI alone
      (without antibody) at various doses to rats. Compared to 30 mg/kg DMI, a dose
      reduction of 30-50% was needed to reduce QRS duration to the same extent as anti
      TCA pretreatment. We conclude that DMI cardiotoxicity was markedly reduced by the
      binding of a relative small fraction of the DMI body burden to anti-TCA. This
      disproportionate effect of DMI binding was not due to the steepness of the DMI
      dose-response curve, nor to slowing of the rate of DMI distribution to tissues.

PMID- 1990240
TI  - Effects of ciglitazone on endogenous plasma islet amyloid polypeptide and insulin
      sensitivity in obese-diabetic viable yellow mice.
AB  - The role of islet amyloid polypeptide, also known as amylin, in insulin
      resistance and in the etiology of diabetes has been a subject of debate.
      Increased plasma amylin levels have been observed in both obese and type II
      diabetic patients. However, data on endogenous amylin levels with relation to
      pharmacological interventions have not been reported. In this study, chronic
      treatment of obese-diabetic viable yellow mice with ciglitazone was shown to
      significantly alter various parameters. Blood glucose and plasma insulin,
      triglyceride, and amylin levels were reduced and glucose tolerance in the
      presence of exogenous insulin was improved. Insulin/amylin ratios which were
      found to be significantly elevated in diabetic mice as compared to normal
      controls, were decreased after ciglitazone treatment. However, observed decreases
      in both amylin and insulin concentrations due to ciglitazone treatment and their
      subsequent increases upon withdrawal of treatment were correlated, suggesting
      cosecretion.

PMID- 1990239
TI  - Alterations in the immune system in cats fed diets with excess cystine.
AB  - As part of an ongoing biochemical study in nutrition we examined blood profiles,
      serum chemistry, lymphocyte transformation and lymphoid pathology in cats fed a
      diet containing 5% cystine with and without taurine. Automated blood counts of
      whole blood samples showed a decrease in red blood cell counts accompanied by a
      significant decrease in hemoglobin and hematocrit in cats fed 5% cystine in the
      absence of taurine compared to cats fed 0.05% taurine (control). A significant
      increase was noted in serum cholesterol in cats fed cystine and cystine/taurine
      compared to cats fed control diets. There were no significant differences in
      lymphocyte transformation using leukocytes isolated from the spleen and blood
      with the mitogens, phytohemagglutinin and pokeweed. However, lymphocyte
      transformation of both spleen and blood without mitogen from the excess cystine
      group were significantly higher than leukocytes from the 0.05% taurine group
      (control). Pathological examination of regional lymph nodes, livers, and spleens
      showed histological abnormalities in cats fed the excess cystine diet. These
      results indicate that there are alterations in the immune system of cats fed a
      diet containing 5% cystine with and without dietary taurine.

PMID- 1990241
TI  - Molecular and cellular biology of cystic fibrosis.

PMID- 1990242
TI  - Human nerve xenografting in nude mouse: experimental study of graft
      revascularization.
AB  - In the nude mouse, the congenital absence of T lymphocytes makes it possible to
      implant human nerve grafts without rejection or iatrogenic modifications (by
      immunosuppression) of human and murine tissues. Medial antebrachial cutaneous
      nerves were harvested from human cadavers 1-18 hours after death. These nerve
      grafts were implanted using different techniques in nude mice. All the grafts
      were macroscopically and microscopically revascularized 3 days after
      implantation. The modifications in time of this vascularization could be studied
      with precision through the use of repeated biopsies. The absence of human blood
      group antigens on the neovessel endothelium suggested a murine origin for
      angiogenesis. In situ DNA hybridizations with human and mouse DNA confirmed this
      origin. The topography of the revascularization (maximal in the perineurium and
      endoneurium) and the almost complete absence of human cells other than Schwann
      cells in the grafts at the peak of angiogenesis (26 days after grafting)
      suggested that Schwann cells had a determining role in graft vascularization. The
      irradiation of the nerve grafts with a dose of 30 grays before implantation did
      not modify significantly their histologic appearance compared to the control
      group, whereas an irradiation of 60 grays led to massive lesions. The
      neurotization of murine axons led to chimerical structures of normal histologic
      appearance, with vascularization similar to that observed in nonneurotized
      nerves. Through chimerism (human Schwann cells, murine vessels and axons) this
      model makes it possible to dissociate the respective role of the host and of the
      nerve graft in angiogenesis and suggests the existence of growth factors produced
      by the human Schwann cells.

PMID- 1990243
TI  - Re-use of the recipient vessels of a microvascular transplant.
AB  - Three cases are described in which a second microvascular free flap, transplanted
      after a delay of several months, was provided perfusion by re-using the recipient
      vessels of the first flap in end-to-end fashion. In each patient healing of the
      second flap was uneventful, and both transplants continue to survive. Prior to
      harvesting the second transplant, a careful intraoperative examination was
      performed in which the vascularity of the original transplant was assessed. In
      each case, recipient vessel re-use represented the least risky of several
      options. The results of the present series suggest that vascularization from the
      transplant bed or surrounding tissues proceeds despite the fact that, initially,
      the only source of blood for the free flap flows through a single axial vessel.
      This single vessel can therefore be divided without loss of the transplant as
      long as the transplant bed has already provided vascularization to the flap. In
      our opinion, the timing of the second procedure and the quality of the transplant
      bed are the key factors in the survival of the transplants.

PMID- 1990244
TI  - Improved survival in a replantation model containing ischemic muscle.
AB  - The effectiveness of superoxide dismutase and allopurinol was evaluated in
      preventing reperfusion injury in Sprague-Dawley rats utilizing a limb
      replantation model after 6 hours of warm ischemia. Immediately prior to
      reperfusion of the replanted limb the animals received (intravenously) either a
      single bolus of superoxide dismutase (16,000 units/kg), a single bolus of
      allopurinol (45 mg/kg), both agents, or only control solutions. In the rats that
      received only control solutions, 30% of the limbs survived the ischemic insult.
      The group that received both superoxide dismutase and allopurinol had a 75% limb
      survival (P = 0.005). The animals that had only superoxide dismutase or
      allopurinol had 58% and 60% of the replanted limbs survive, respectively. This
      study suggests that the administration of superoxide dismutase and allopurinol
      may be helpful in the prevention of reperfusion injury in skeletal muscle in an
      acute injury setting (without pretreatment) and may thereby improve limb salvage
      after a significant ischemic period.

PMID- 1990245
TI  - Experimental microvenous reconstructions with Gore-Tex polytetrafluoroethylene
      prosthesis implanted by means of the sleeve anastomotic technique.
AB  - Polytetrafluoroethylene (PTFE) prostheses (Gore-Tex; ID, 1 mm; length, 5-7 mm;
      wall thickness, 0.2 mm; fibril length, 30 microns, n = 28) were implanted into
      the rat femoral vein by means of the sleeve anastomotic technique to enhance the
      patency rate. In the control group, PTFE prostheses (n = 8) were implanted by
      means of the end-to-end technique. In the experimental group patency and healing
      of the PTFE prostheses were evaluated at 1 day (n = 4), 1 week (n = 6), 3 weeks
      (n = 6), 6 weeks (n = 6), and 12 weeks (n = 6) after implantation by means of
      macroscopic inspection and routine light and scanning electron microscopy. All
      prostheses, except one at 1 week after implantation, were patent at the time of
      removal. All of the microvenous prostheses were completely covered by an
      endothelial layer at 3, 6, and 12 weeks after implantation. Occasionally some
      smooth muscle-like cells could be found underneath this endothelial layer, but
      stenosis was never observed at the anastomotic sites. Only scarce tissue ingrowth
      was observed in the wall of the PTFE prostheses. In the control group, all
      prostheses, except one prosthesis after 3 weeks, were found to be occluded. An
      occlusive mural thrombus was found firmly attached at the anastomoses at 1 day,
      and an organized thrombus at 3 weeks after implantation. The patent prosthesis
      demonstrated complete endothelial healing. These results demonstrate the
      importance of the sleeve anastomotic technique and the potential of PTFE
      prostheses as a microvenous conduit when implanted by means of the sleeve
      anastomotic technique in experimental reconstructive microvascular procedures.

PMID- 1990246
TI  - Mural repair following obliteration of aneurysms. Part III: Pathomorphological
      effects of Nd:YAG laser on aneurysm obliteration.
AB  - Twenty-four experimental aneurysms were created in rat carotid arteries using the
      venous pouch technique. Four to twelve weeks later, these aneurysms were totally
      obliterated by the external application of Nd:YAG laser. The aneurysmal dome and
      neck were both exposed to the laser using low amplitude (1-2 W) at continuous or
      repeat intervals (0.3 sec on/0.1 sec off). Small aneurysms were easily
      obliterated without external signs of necrosis, whereas aneurysms larger than 2
      mm required complete coagulation resulting in a charcoal-like appearance. At
      varying intervals (30 min, 7 days, 3 weeks, 6 weeks), the obliterated aneurysms
      were harvested and evaluated using the scanning electron microscope and standard
      histological techniques. The results indicate that the effects of the laser on
      the aneurysm and parent vessel are similar to those encountered following the
      application of bipolar coagulation with massive coagulation necrosis of the
      aneurysmal neck and dome. Notably, however, the extension of this process onto
      the parent vessel involving especially the endothelium surrounding the aneurysm
      orifice (commonly seen with bipolar coagulation) is minimal following laser
      coagulation. There appears to be a protective effect on the parent vessel
      endothelium by blood flow through the vessel. On this basis, it appears that the
      laser may be an alternative method of aneurysmal coagulation; the use of laser
      entails less manipulation of the aneurysm. The Nd:YAG laser may be a useful
      adjunct in the surgical obliteration of clinical cerebral artery aneurysms,
      especially small ones.

PMID- 1990247
TI  - Simultaneous comparison of pre- and post-microanastomotic hemodynamic profiles
      using a Tandem Doppler Probe.
AB  - The use of High-Frequency Pulsed Doppler Ultrasound (HFPDU) for evaluation of
      microvascular hemodynamics is well established. Due to technical limitations of
      existing probes, quantitation of anastomotic stenoses and detailed waveform
      analyses are difficult to perform and impractical for clinical use. We present a
      new Tandem Doppler Probe (TDP) for simple and accurate study of blood flow in
      vessels smaller than 1 mm in diameter. Its unique ability to compare the pre- and
      post-anastomotic waveforms simultaneously allows for quantitative detection of
      anastomotic narrowing of as little as 5%, as well as identification of subtle
      pathologic anastomotic waveform changes not seen with single probes. Such early
      and precise delineation of anastomotic problems in the operating room can provide
      an invaluable, objective assessment of the technical adequacy of the anastomoses
      as well as an important baseline for later post-operative monitoring of free
      tissue transfers with implantable Doppler devices.

PMID- 1990248
TI  - Rat femoral vein-to-vein grafts as a microvascular practice model: factors that
      influence patency.
AB  - The rat femoral vein has become a standard model for microvascular anastomosis
      practice as well as for research investigations into various manipulative
      influences upon venous patency. Although vein grafts to the rat artery are the
      focus of many experimental studies, few reports have investigated vein-to-vein
      grafts. This study examines the short-term patency (1-3 days) of vein grafts
      interpositioned to the rat femoral vein. Several factors are studied for their
      ability to alter the patency rate. The results indicate that patency is difficult
      to achieve following the creation of a second serial anastomosis (construction of
      a vein-to-vein graft). Systemic heparin consistently improves patency rates, and
      trends toward increased patency are seen for reduction in longitudinal tension of
      the repaired vessel. It is also implied that a deeper understanding of venous
      hemodynamics and thrombotic events may lead to improved methodologies in the
      clinical applications of microvenous repairs. These results indicate that rat
      vein-to-vein grafts may provide a challenging microvascular training model, while
      introducing the novice microsurgeon to some of the complicating factors
      encountered with microvascular grafting.

PMID- 1990249
TI  - Carotid bifurcation reconstruction using y-shaped microvascular grafts: an
      experimental study in rats.
AB  - Reconstruction of the carotid bifurcation was performed in rats using y-shaped
      microvascular grafts in an attempt to examine the feasibility of using such
      grafts in intracranial vascular reconstruction, especially for vessels with
      bifurcations. Twenty y-shaped microarterial grafts were obtained from the carotid
      bifurcation of donor rats, while 20 y-shaped microvenous grafts were obtained
      from the femoral veins of the rats. The patency rate of arterial grafts and
      venous grafts were 75% and 97%, respectively. Anastomotic aneurysms frequently
      occurred in both arterial grafts (45%) and venous grafts (60%). Results of
      histological examinations concluded that these aneurysms were false aneurysms. We
      discuss the reasons for aneurysm formation and technical issues that might
      improve the experimental results with regard to patency and aneurysm formation.

PMID- 1990250
TI  - Inhibition of epinephrine-induced vasospasm with adrenoreceptor blockade in the
      rat cremaster muscle.
AB  - This study demonstrates that intravenous epinephrine causes arterial vasospasm,
      but not venous constriction, in the microcirculation of the rat cremaster muscle.
      This effect can be blocked by a smooth muscle relaxant such as papaverine or an
      alpha receptor antagonist such as phentolamine. Circulating vasospastic agents
      such as epinephrine are important determinants of microcirculatory blood flow,
      and inhibition by pharmacologic means may enhance blood flow and survival in
      microvascular surgery.

PMID- 1990251
TI  - Some factors affecting the survival of venous flaps: an experimental study.
AB  - The inferior epigastric venous flap of the rat was chosen for experimental
      studies of vascular flow alterations. The long saphenous vein was not selected
      for use; preliminary studies involving forced retrograde injection demonstrated
      that it drains blood primarily from the leg and foot, not from its overlying
      skin. Eight different flap designs were studies: group A, saphenous flap, simple
      isolation with pedicle; group B, inferior epigastric flap, simple isolation with
      pedicle; group C, inferior epigastric flap, simple isolation with interpositioned
      Silastic sheet; group D, cross-transferred venous pressure arterial flap; group
      E, cross-transferred, arterialised venous flap; group F, arterialized venous
      flap, in which arterial blood was shunted away via the main vein: group G, cross
      transferred venous pressure venous flap; and group K. control, nonvascularized
      flap. Three more groups (H, I, J) were introduced by repeating the flap designs
      of groups E, F, and G but preceded by forced perfusion of the venous system using
      5 cc of normal saline at 200 mm Hg. The best results were obtained with groups B,
      C, E, H, and I. The other flaps necrosed. The results are discussed based on the
      assumption that true retrograde venous blood flow does occur.

PMID- 1990252
TI  - Treatment patterns in low-grade non-Hodgkin's lymphomas: a single institution
      study.
AB  - Ninety-two cases of low-grade non-Hodgkin's lymphoma were examined
      retrospectively to assess to what extent treatment deferral is practiced at a
      single university hospital with a local referral base. Clinical characteristics
      of this patient group were also analyzed; 70% of these cases were of nodular
      lymphocytic, poorly differentiated (NLPD) histology, and 74% were stage III or
      IV. Twenty-two cases were not treated initially. Nine eventually required
      treatment at a median of 16 months. Survival did not differ based on whether
      treatment was initially deferred. Nodal progression was the most common reason
      for beginning treatment after initial deferral, and most cases of advanced stage
      disease required treatment because of nodal involvement or B-type symptoms at
      diagnosis. Presence of intra-abdominal adenopathy often prompted initial
      treatment even in asymptomatic cases. In this series, as compared to previously
      reported series of treatment-deferred cases, more patients were judged to require
      treatment at disease outset, and the median time to treatment in those in whom
      treatment was initially deferred but then instituted was shorter. Despite this,
      for the entire population, 69% of total follow-up time was spent off therapy.

PMID- 1990253
TI  - Efficacy of postoperative chemotherapy using cisplatin plus etoposide in young
      children with brain tumors.
AB  - Neuraxis radiation therapy (RT) for primary intracranial tumors is associated
      with major late effects if administered to very young children. To control
      residual tumor and to delay RT, we treated eight young children (median age 6.5
      months) with primary central nervous system (CNS) tumors using combination
      chemotherapy: cisplatin, 20 mg/M2/day plus VP-16, 75 mg/M2/day i.v. for 5 days,
      given q. 3-6 weeks for 8 cycles. The tumors were medulloblastoma (one), malignant
      ependymoma (two), primitive neuroectodermal tumor PNET (two), malignant glioma
      (two), astrocytoma (one). Six had measurable disease; three had positive
      cerebrospinal fluid (CSF) cytopathology. All patients with measurable tumor had
      initial objective responses (three) complete response [CR], one partial response
      [PR], two minor response [MR], including cytopathology (three CR of three) and
      metastatic deposits (two CR of two). One patient relapsed during chemotherapy.
      Median time to disease progression was 17.5 months; median survival was 34
      months. Three patients, none of whom received RT, have prolonged progression-free
      intervals of 47-67 months to date. Neurodevelopmental progress continued during
      and after chemotherapy. Chemotherapy toxicity was mild. Median neutrophil nadir
      was 312/mm3, platelets 72,000. Fever during neutropenia occurred in six of 61
      courses. Moderate high-frequency auditory losses were detected in three patients,
      and mild renal injury (GFR less than 70 ml/min) was detected in two of seven
      evaluable children. This pilot study demonstrates the apparent efficacy and mild
      toxicity of 5 day courses of cisplatin plus VP-16, with delayed RT, in young
      children with CNS neoplasms. A POG treatment protocol that incorporates cisplatin
      plus VP-16 is evaluating primary chemotherapy with delayed radiotherapy in larger
      numbers of pediatric brain tumor patients.

PMID- 1990254
TI  - Childhood malignant lymphoma of bone.
AB  - From 1974 to 1987, 450 children with non-Hodgkins' lymphoma (NHL) were seen at
      the Institut Gustave Roussy (IGR); 14 children had malignant lymphoma of bone
      (MLB). Eleven of the 14 were newly diagnosed, whereas three presented in relapse.
      Nine patients presented with multifocal bone involvement. The median age of these
      eight girls and six boys was 9.5 years (range 1.25-15 years). Bone pain was
      present in all patients as the initial symptom. Evaluation included physical
      examination, routine serum chemistries, complete blood count, chest
      roentgenography, skeletal survey, radionuclide bone scan, lumbar puncture, bone
      marrow aspiration, and intravenous pyelography, and/or abdominal ultrasonography.
      Hypercalcemia was found in six patients. Biopsy was performed in 12 patients,
      revealing high-grade lymphoblastic lymphomas in all. In two patients diagnosis
      was made on cytological examination of bone marrow aspirate. Immunophenotyping in
      four cases, demonstrated non-B, non-T cell origin in three and pre-B cell origin
      in one. Three patients were treated prior to 1982 with
      Cyclophosphamide/Oncovin/Prednisone/ADriamycin (COPAD) and seven patients, seen
      after 1982, were treated with a modified LSA2L2 protocol (LMT). None of the
      previously untreated patients received radiotherapy. All patients treated with
      COPAD have died, whereas four out of seven treated with LMT are alive with a
      median follow up of 51 months (range 36-82 months). One child treated on a pilot
      study died. One of the three children seen at relapse is disease-free with a
      follow-up of 98 months after high-dose chemotherapy followed by autologous bone
      marrow transplantation (ABMT). Five out of six patients presenting with
      hypercalcemia have died. Results with LMT are encouraging and together with
      published results suggest that sufficiently intensive chemotherapy can result in
      complete remission and cure in MLB. Radiotherapy does not seem to be necessary,
      avoiding possible serious long-term effects. Hypercalcemia is a bad prognostic
      feature.

PMID- 1990255
TI  - Infant leukemia in Japan: clinical and biological analysis of 48 cases.
AB  - Forty-eight Japanese infants with acute lymphoid leukemia (ALL) (n = 24) and
      acute nonlymphoid leukemia (ANLL) (n = 24) were analyzed on the basis of clinical
      and laboratory data. Morphologically, 20 of the 24 infants with ALL were of the
      FAB L1 type, and 20 of the 24 infants with ANLL were of the M4 or M5 type.
      Markedly enlarged liver and spleen, and hyperleukocytosis (more than
      50,000/microliters) were seen in 9, 12, and 14 infants with ALL and 10, 11, and
      10 infants with ANLL, respectively. Initial CNS leukemia was evident in 2
      infants. Chromosome studies of the leukemic cells showed abnormal karyotypes in 9
      of the 21 infants with ALL and 19 of the 22 infants with ANLL, consisting mainly
      of translocation 11, 12, and inversion 16. By surface marker analysis, only 7 of
      the 22 infants with ALL (32%) were diagnosed as having common ALL (HLA-DR+,
      CD19+, CD10+). Of the 15 infants with ANLL, 12 and 5 infants also showed
      reactivity to HLA-DR and CD19, respectively. All of the 5 ANLL infants with
      lymphoid markers showed different leukemic cell features at the time of relapse.
      Twelve of the 19 infants with ALL (63%) who achieved a complete remission
      relapsed within the first 2 years; 8 of the 21 with ANLL (38%) relapsed within
      the first year. Analysis of event-free survival shows that the ALL infants with
      hyperleukocytosis have a poorer prognosis than those without hyperleukocytosis (p
      less than 0.05). Infant leukemia originates in a multipotent cell with lymphoid
      and myeloid features, and intensive multiagent chemotherapy is necessary for the
      treatment of infants with acute leukemia.

PMID- 1990256
TI  - Lepto-meningeal melanosis.

PMID- 1990257
TI  - Gastrointestinal lymphoma.
AB  - Primary GI lymphoma is a rare clinical entity. A primary nodal tumor should be
      ruled out. Symptoms may not be localizing and B symptoms are less common. A
      tissue diagnosis, preferably by transmural biopsy for small intestinal
      involvement, often reveals a high-grade morphology. The staging work-up should
      include a bone marrow examination, although formal staging laparatomy is not
      always required. Patients with Mushoff stage IE or IIE1 disease do better than
      those with extraregional nodal disease or distant metastatic involvement.
      Surgical resection with clear margins is required in order to maximize the
      changes for cure. Chemotherapy or radiotherapy may give a survival advantage when
      used as adjuvant treatment for selected stage IE and IIE disease. Chemotherapy
      should be used after surgical debulking in more advanced disease in order to
      minimize the chance for bleeding or performation. Future randomized, multi
      institutional trials will give more direction as to the best modes of management.

PMID- 1990258
TI  - Myelofibrosis in a child suffering from a hypereosinophilic syndrome with trisomy
      8: response to corticotherapy.
AB  - The idiopathic hypereosinophilic syndrome (IHS) is extremely rare in childhood
      and relationships of this syndrome with myeloproliferative diseases are
      controversial. We reported the observation of a 7-year-old girl suffering from an
      IHS with myelofibrosis. A clonal cytogenetic abnormality, trisomy 8, was detected
      in the bone marrow cells of this child. This is the decisive proof of a
      myeloproliferative disorder. IHS with myelofibrosis is usually considered as
      unresponsive to corticotherapy. In our case, corticotherapy resulted in a rapid,
      complete, and lasting disappearance of myelofibrosis. Complete remission of the
      disease, however, was not achieved and the trisomy 8 persisted after treatment.

PMID- 1990259
TI  - A child with esthesioneuroblastoma with metastases to the spinal cord and the
      bone marrow.
AB  - Esthesioneuroblastoma is a rare tumor in children, and the correct diagnosis may
      be difficult, as is demonstrated in this case report. A 5-year-old girl was
      diagnosed with this tumor, which was incurable and behaved like a neuroblastoma,
      sending metastases to the bone marrow and invading the cranium and the spinal
      canal.

PMID- 1990260
TI  - Vascular events in patients receiving high-dose infusional 5-fluorouracil-based
      chemotherapy: the University of Chicago experience.
AB  - In a retrospective review, 22 of a total of 244 patients (9%) patients with head
      and neck or gastrointestinal cancer who were treated with infusional 5
      fluorouracil (5-FU)-based chemotherapy regimens experienced thrombotic vascular
      events. These events occurred concurrently with treatment or several months
      following the completion of therapy and consisted mainly of cardiac arrhythmias,
      myocardial infarction, sudden death, and thromboembolism. The temporal
      relationship of these vascular events to the time of treatment suggests that
      infusional 5-FU may have been the underlying cause.

PMID- 1990261
TI  - Defective regulation of mitogen-activated protein kinase activity in a 3T3 cell
      variant mitogenically nonresponsive to tetradecanoyl phorbol acetate.
AB  - Mitogen-activated protein (MAP) kinase is a serine/threonine-specific protein
      kinase which is activated in response to various mitogenic agonists (e.g.,
      epidermal growth factor, insulin, and the tumor promoter tetradecanoyl phorbol
      acetate [TPA]) and requires both threonine and tyrosine phosphorylation for
      activity. This enzyme has recently been shown to be identical or closely related
      to pp42, a protein which becomes tyrosine phosphorylated in response to mitogenic
      stimulation. Neither the kinases which regulate MAP kinase/pp42 nor the in vivo
      substrates for this enzyme are known. Because MAP MAP kinase is activated and
      phosphorylated in response both to agents which stimulate tyrosine kinase
      receptors and to agents which stimulate protein kinase C, a serine/threonine
      kinase, we have examined the regulation and phosphorylation of this enzyme in 3T3
      TNR9 cells, a variant cell line partially defective in protein kinase C-mediated
      signalling. In this communication, we show that in the 3T3-TNR9 variant cell
      line, TPA does not cause the characteristically rapid phosphorylation of pp42 or
      the activation and phosphorylation of MAP kinase. This defective response is not
      due to the absence of the MAP kinase/pp42 protein itself because both tyrosine
      phosphorylation of MAP kinase/pp42 and its enzymatic activation could be induced
      by platelet-derived growth factor in the 3T3-TNR9 cells. Thus, the defect in
      these variant cells apparently resides in some aspect of the regulation of MAP
      kinase phosphorylation. Since the 3T3-TNR9 cells are also defective with respect
      to the TPA-induced increase in ribosomal protein S6 kinase, these in vivo results
      reinforce the earlier in vitro finding that MAP kinase can regulate S6 kinase
      activity. These findings suggest a key role for MAP kinase in a kinase cascade
      cascade involved in the control of cell proliferation.

PMID- 1990262
TI  - Induction by ionizing radiation of the gadd45 gene in cultured human cells: lack
      of mediation by protein kinase C.
AB  - The effect of ionizing radiation on the expression of two DNA-damage-inducible
      genes, designated gadd45 and gadd153, was examined in cultured human cells. These
      genes have previously been shown to be strongly and coordinately induced by UV
      radiation and alkylating agents in human and hamster cells. We found that the
      gadd45 but not the gadd153 gene is strongly induced by X rays in human cells. The
      level of gadd45 mRNA increased rapidly after X rays at doses as low as 2 Gy.
      After 20 Gy of X rays, gadd45 induction, as measured by increased amounts of
      mRNA, was similar to that produced by the most effective dose of the alkylating
      agent methyl methanesulfonate. No induction was seen after treatment of either
      human or hamster cells with 12-O-tetradecanoylphorbol-13-acetate, a known
      activator of protein kinase C (PKC). Therefore, gadd45 represents the only known
      mammalian X-ray-responsive gene whose induction is not mediated by PKC. However,
      induction was blocked by the protein kinase inhibitor H7, indicating that
      induction is mediated by some other kinase(s). Sequence analysis of human and
      hamster cDNA clones demonstrated that this gene has been highly conserved and
      encodes a novel 165-amino-acid polypeptide which is 96% identical in the two
      species. This gene was localized to the short arm of human chromosome 1 between
      p12 and p34. When induction in lymphoblast lines from four normal individuals was
      compared with that in lines from four patients with ataxia telangiectasia,
      induction by X rays of gadd45 mRNA was less in the cell lines from this cancer
      prone radiosensitive disorder. Our results provide evidence for the existence of
      an X-ray stress response in human cells which is independent of PKC and which is
      abnormal in taxia telangiectasia.

PMID- 1990263
TI  - Nuclear factor kappa B activates proenkephalin transcription in T lymphocytes.
AB  - Upon activation, T lymphocytes accumulate high levels of the neuropeptide
      enkephalin which correlate with high levels of proenkephalin mRNA in the cells.
      Here we investigated the transcriptional basis for these changes. The
      proenkephalin promoter contains a sequence GGGGACGTCCCC, named B2, which is
      similar to the kappa B sequence GGGGACTTTCC, the binding site of the
      transcription factor nuclear factor (NF)-kappa B. Activation of T lymphocytes
      induces an NF-kappa B-like binding activity to the B2 site, concomitant with
      activation of the proenkephalin promoter. Mutations at the B2 site abolish this
      transcriptional activation. The purified homodimer (two p50s) of the DNA-binding
      subunit of NF-kappa B binds the B2 site of proenkephalin relatively better than
      does the heterotetramer (two p65s plus two p50s) form of the factor. Thus, it
      appears that the T-cell-specific activation of the proenkephalin promoter is
      mediated by NF-kappa B. However, as NF-kappa B is ubiquitous and the
      transcriptional activation through the B2 site is T cell specific, yet another T
      cell-specific factor which synergizes with NF-kappa B should be considered.

PMID- 1990264
TI  - The 5'-flanking region of the mouse thymidylate synthase gene is necessary but
      not sufficient for normal regulation in growth-stimulated cells.
AB  - The thymidylate synthase (TS) gene is a housekeeping gene that is expressed at
      much higher levels in proliferating cells than in quiescent cells. We have
      studied the role of the TS 5'-flanking sequences in regulating the level of
      expression of the mouse TS gene. A variety of chimeric TS minigenes that contain
      different promoters linked either to the TS coding region (with or without
      introns) or to the chloramphenicol acetyltransferase (CAT) coding region were
      constructed. The activities of the minigenes were determined by transfecting them
      into cultured cells and measuring the levels of mRNA or enzyme derived from the
      chimeric genes. We found that the mouse TS promoter had about the same strength
      as the simian virus 40 early promoter but was significantly stronger than the
      herpes simplex virus thymidine kinase promoter. Stable transfection studies
      revealed that minigenes consisting of the normal TS promoter (extending to -1
      kb), coding region, and polyadenylation signal were regulated normally in
      response to growth stimulation. When the TS promoter was replaced by the simian
      virus 40 early promoter or by a TS promoter that retained only 60 nucleotides
      upstream of the first transcriptional start site, the minigene was expressed
      constitutively. A minigene consisting of the TS promoter (extending to -1 kb)
      linked to the CAT coding region was also expressed constitutively. These
      observations indicate that sequences upstream of the transcriptional start sites
      of the TS gene are necessary, although not sufficient, for normal growth
      regulated expression of the mouse TS gene.

PMID- 1990265
TI  - Degradation of a-factor by a Saccharomyces cerevisiae alpha-mating-type-specific
      endopeptidase: evidence for a role in recovery of cells from G1 arrest.
AB  - Mating response between opposite mating types of Saccharomyces cerevisiae is
      dependent upon alpha factor, a tridecapeptide, and a-factor, an isoprenylated,
      methyl esterified dodecapeptide whose interaction with the alpha target cell has
      not been characterized. We report on the first biochemical and physiological
      evidence of an alpha-mating-type-specific a-factor-degrading activity.
      Radioiodinated a-factor was used to identify the a-factor-degrading activity,
      which is cell associated, endoproteolytic, and not required for response to
      pheromone. a-factor degradation was not energy dependent, nor did it require
      pheromone internalization or interaction with its receptor. Phenylmethylsulfonyl
      fluoride and tosyl-L-arginyl-methyl ester inhibited degradation of a-factor and
      increased the time required by alpha cells to recover from a-factor-induced
      growth arrest and morphological alteration, providing evidence that a-factor
      degradation plays a role in the recovery of alpha cells from the pheromone
      response.

PMID- 1990267
TI  - The role of RAP1 in the regulation of the MAT alpha locus.
AB  - The RAP1 gene of Saccharomyces cerevisiae encodes an abundant DNA-binding
      protein, also known as GRF1, TBA, or TUF, that binds to many sites in the yeast
      genome in vitro. These sites define a consensus sequence, [sequence: see text],
      and deletion analyses of genes that contain this sequence have implicated the
      involvement of RAP1 in numerous cellular processes, including gene activation and
      repression. The MAT alpha locus, required for determination of the alpha cell
      type in yeast cells, contains a RAP1 binding site; this site coincides with the
      MAT alpha upstream activating sequence (UAS) and is necessary for expression of
      the two genes encoded by the MAT alpha locus, MAT alpha 1 and MAT alpha 2. We
      show that the MAT alpha UAS is sufficient to activate transcription from a
      promoterless gene fusion of the yeast CYC1 upstream region and the lacZ gene.
      Constructs containing only the MAT alpha UAS generated elevated levels of beta
      galactosidase activity which were indistinguishable from those of constructs
      containing the entire MAT alpha intergenic region. Further, the MAT alpha UAS has
      an intrinsic polarity of transcriptional activation; transcription of CYC1-lacZ
      was six- to sevenfold higher when the UAS was oriented in the direction normally
      associated with MAT alpha 2 transcription. Point mutations in the MAT alpha UAS
      that reduce MAT alpha expression three- to fivefold resulted in a bi-mating
      phenotype, while a mutation that reduced MAT alpha expression still further
      resulted in an a-mating phenotype. We isolated plasmids from a high-copy-number
      yeast library that suppressed the bi-mating defect of point mutations in the MAT
      alpha UAS, and the most effective dosage suppressor contained the gene encoding
      RAP1. A temperature-sensitive rap1 mutant bi-mates at the semipermissive
      temperature. Double mutants at rap1 and mat alpha mate exclusively as a cells, at
      all temperatures, and do not express detectable levels of MAT alpha RNA. These
      data provide evidence that the RAP1 gene product functions at the MAT alpha UAS
      in vivo.

PMID- 1990266
TI  - UHF-1, a factor required for maximal transcription of early and late sea urchin
      histone H4 genes: analysis of promoter-binding sites.
AB  - A protein, denoted UHF-1, was found to bind upstream of the transcriptional start
      site of both the early and late H4 (EH4 and LH4) histone genes of the sea urchin
      Strongylocentrotus purpuratus. A nuclear extract from hatching blastulae
      contained proteins that bind to EH4 and LH4 promoter fragments in a band shift
      assay and produced sharp DNase I footprints upstream of the EH4 gene (from -133
      to -106) and the LH4 gene (from -94 to -66). DNase I footprinting performed in
      the presence of EH4 and LH4 promoter competitor DNAs indicated that UHF-1 binds
      more strongly to the EH4 site. A sequence match of 11 of 13 nucleotides was found
      within the two footprinted regions: [sequence: see text]. Methylation
      interference and footprinting experiments showed that UHF-1 bound to the two
      sites somewhat differently. DNA-protein UV cross-linking studies indicated that
      UHF-1 has an electrophoretic mobility on sodium dodecyl sulfate-acrylamide gels
      of approximately 85 kDa and suggested that additional proteins, specific to each
      promoter, bind to each site. In vitro and in vivo assays were used to demonstrate
      that the UHF-1-binding site is essential for maximal transcription of the H4
      genes. Deletion of the EH4 footprinted region resulted in a 3-fold decrease in
      transcription in a nuclear extract and a 2.6-fold decrease in expression in
      morulae from templates that had been injected into eggs. In the latter case,
      deletion of the binding site did not grossly disrupt the temporal program of
      expression from the injected EH4 genes. LH4 templates containing a 10-bp deletion
      in the consensus region or base substitutions in the footprinted region were
      transcribed at 14 to 58% of the level of the wild-type LH4 template. UHF-1 is
      therefore essential for maximal expression of the early and late H4 genes.

PMID- 1990268
TI  - A role for CDC7 in repression of transcription at the silent mating-type locus
      HMR in Saccharomyces cerevisiae.
AB  - The mating-type genes at MAT in Saccharomyces cerevisiae are expressed, whereas
      the same genes located at HML and HMR are transcriptionally repressed. The DNA
      element responsible for repression at HMR has been termed a silencer and contains
      an autonomous replication sequence, a binding site for GRFI/RAPI, and a binding
      site for ABFI. A double-mutant HMR-E silencer that contains single nucleotide
      substitutions in both the GRFI/RAPI- and ABFI-binding sites no longer binds
      either factor in vitro, nor represses transcription at HMR in vivo. In MAT alpha
      cells, this derepression of a information results in a nonmating phenotype.
      Second-site suppressor mutations were isolated that restored the alpha mating
      phenotype to MAT alpha cells containing the double-mutant silencer. One of these
      suppressors, designated sas1-1, conferred a temperature-sensitive lethal
      phenotype to the cell. SAS1 was found to be identical to CDC7, a gene which
      encodes a protein kinase required for the initiation of DNA replication. This new
      allele of CDC7 was designated cdc7-90. cdc7-90 restored the alpha mating
      phenotype by restoring silencing. The original allele of CDC7, isolated on the
      basis of the cell cycle phenotype it confers, also restored silencing, and
      overexpression of CDC7 interfered with silencing. cdc7-90 did not restore
      detectable binding of GRFI/RAPI or ABFI to the double-mutant silencer in vitro.
      These results indicate that a reduced level of CDC7 function restores silencing
      to a locus defective in binding two factors normally required for silencing.

PMID- 1990269
TI  - Macronuclear transformation with specific DNA fragments controls the content of
      the new macronuclear genome in Paramecium tetraurelia.
AB  - A previously isolated mutant cell line called d48 contains a complete copy of the
      A surface antigen gene in the micronuclear genome, but the gene is not
      incorporated into the macronucleus. Previous experiments have shown that a
      cytoplasmic factor made in the wild-type macronucleus can rescue the mutant.
      Recently, S. Koizumi and S. Kobayashi (Mol. Cell. Biol. 9:4398-4401, 1989)
      observed that injection of a plasmid containing the A gene into the d48
      macronucleus rescued the cell line after autogamy. It is shown here that an 8.8
      kb EcoRI fragment containing only a portion of the A gene coding region is
      sufficient for the rescue of d48. The inability of other A gene fragments to
      rescue the mutant shows that this effect is dependent upon specific Paramecium
      DNA sequences. Rescue results in restoration of the wild-type DNA restriction
      pattern in the macronucleus. These results are consistent with a model in which
      the macronuclear A locus normally makes an additional gene product that is
      required for correct processing of the micronuclear copy of the A gene.

PMID- 1990270
TI  - The K-fgf/hst oncogene induces transformation through an autocrine mechanism that
      requires extracellular stimulation of the mitogenic pathway.
AB  - The K-fgf/hst oncogene encodes a secreted growth factor of the fibroblast growth
      factor (FGF) family. The ability of K-fgf-transformed cells to grow in soft agar
      and in serum-free medium is inhibited by anti-K-FGF neutralizing antibodies,
      consistent with an autocrine mechanism of transformation. The transformed
      properties of clones that express high levels of K-FGF are, however, only
      partially affected. To better define the autocrine mechanism of transformation by
      K-fgf and to determine whether receptor activation could occur intracellularly,
      we constructed two mutants of the K-fgf cDNA. Deletion of the sequences encoding
      the signal peptide suppressed K-fgf ability to induce foci in NIH 3T3 cells. A
      few morphologically transformed colonies were observed in cotransfection
      experiments, and they were found to express high levels of cytoplasmic K-FGF.
      However, their ability to grow in serum-free medium and in soft agar was
      inhibited by anti-K-FGF antibodies. Addition of a sequence encoding the KDEL
      endoplasmic reticulum and Golgi retention signal to the K-fgf cDNA led to
      accumulation of the growth factor in intracellular compartments. The ability of
      the KDEL mutant to induce foci in NIH 3T3 cells was much lower than that of the
      wild-type cDNA, and also in this case the transformed phenotype was reverted by
      anti-K-FGF antibodies. These and other findings indicate that the transformed
      phenotype of cells expressing a nonsecretory K-FGF is due to the extracellular
      activation of the receptor by the small amounts of growth factor that these cells
      still release. Thus, transformation by K-fgf appears to be due to an autocrine
      growth mechanisms that requires activation of the mitogenic pathway at the cell
      surface.

PMID- 1990271
TI  - B-cell- and myocyte-specific E2-box-binding factors contain E12/E47-like
      subunits.
AB  - Recent studies have identified a family of DNA-binding proteins that share a
      common DNA-binding and dimerization domain with the potential to form a helix
      loop-helix (HLH) structure. Various HLH proteins can form heterodimers that bind
      to a common DNA sequence, termed the E2-box. We demonstrate here that E2-box
      binding B-cell- and myocyte-specific nuclear factors contain subunits which are
      identical or closely related to ubiquitously expressed (E12/E47) HLH proteins.
      These biochemical function for E12/E47-like molecules in mammalian
      differentiation, similar to the genetically defined function of daughterless in
      Drosophila development.

PMID- 1990273
TI  - Mice bearing the E mu-myc and E mu-pim-1 transgenes develop pre-B-cell leukemia
      prenatally.
AB  - Previously, it has been shown that E mu-pim-1 transgenic mice are predisposed to
      T-cell lymphomas, whereas E mu-myc transgenic mice are predisposed to pre-B-cell
      lymphomas. Here we show that double-transgenic E mu-myc E mu-pim-1 mice exhibit
      pre-B-cell leukemia in utero. Upon transplantation into recipient mice, embryo
      derived double-transgenic leukemic cells frequently progressed to highly
      malignant monoclonal tumors, indicating that additional (epi)genetic events had
      occurred during the progression of the disease.

PMID- 1990272
TI  - The DAL81 gene product is required for induced expression of two differently
      regulated nitrogen catabolic genes in Saccharomyces cerevisiae.
AB  - We demonstrate that the DAL81 gene, previously thought to be specifically
      required for induced expression of the allantoin pathway genes in Saccharomyces
      cerevisiae, functions in a more global manner. The data presented show it to be
      required for utilization of 4-aminobutyrate as a nitrogen source and for 4
      aminobutyrate-induced increases in the steady-state levels of UGA1 mRNA. The
      DAL81 gene encodes a 970-amino-acid protein containing sequences homologous to
      the Zn(II)2Cys6 motif and two stretches of polyglutamine residues. Deletion of
      sequences homologous to the Zn(II)2Cys6 motif did not result in a detectable loss
      of function. On the other hand, loss of one of the polyglutamine stretches, but
      not the other, resulted in a 50% loss of DAL81 function.

PMID- 1990274
TI  - Nuclear and cytoplasmic location of the FER tyrosine kinase.
AB  - The location of the FER protein within the cell was investigated by using
      subcellular fractionation and immunofluorescence. FER was found in the cytoplasm
      and in the nucleus, where it was associated with the chromatin fraction. Its
      ubiquitous expression and its subcellular location indicate that it may be
      involved in key regulatory processes.

PMID- 1990275
TI  - Functional analysis of chimeric genes obtained by exchanging homologous domains
      of the mouse mdr1 and mdr2 genes.
AB  - A full-length cDNA clone for the mouse mdr1 gene can confer multidrug resistance
      when introduced by transfection into otherwise drug-sensitive cells. In the same
      assay, a full-length cDNA clone for a closely related member of the mouse mdr
      gene family, mdr2, fails to confer multidrug resistance. To identify the domains
      of mdr1 which are essential for multidrug resistance and which may be
      functionally distinct in mdr2, we have constructed chimeric cDNA molecules in
      which discrete domains of mdr2 have been introduced into the homologous region of
      mdr1 and analyzed these chimeras for their capacity to transfer drug resistance.
      The two predicted ATP-binding domains of mdr2 were found to be functional, as
      either could complement the biological activity of mdr1. Likewise, a chimeric
      molecule in which the highly sequence divergent linker domain of mdr2 had been
      introduced in mdr1 could also confer drug resistance. However, the replacement of
      either the amino- or carboxy-terminus transmembrane (TM) domain regions of mdr1
      by the homologous segments of mdr2 resulted in inactive chimeras. The replacement
      of as few as two TM domains from either the amino (TM5-6) or the carboxy (TM7-8)
      half of mdr1 by the homologous mdr2 regions was sufficient to destroy the
      activity of mdr1. These results suggest that the functional differences detected
      between mdr1 and mdr2 in our transfection assay reside within the predicted TM
      domains.

PMID- 1990276
TI  - A variant octamer motif in a Xenopus H2B histone gene promoter is not required
      for transcription in frog oocytes.
AB  - Xenopus oocytes, arrested in G2 before the first meiotic division, accumulate
      histone mRNA and protein in the absence of chromosomal DNA replication and
      therefore represent an attractive biological system in which to examine histone
      gene expression uncoupled from the cell cycle. Previous studies have shown that
      sequences necessary for maximal levels of transcription in oocytes are present
      within 200 bp at the 5' end of the transcription initiation site for genes
      encoding each of the five major Xenopus histone classes. We have defined by site
      directed mutagenesis individual regulatory sequences and characterized DNA
      binding proteins required for histone H2B gene transcription in injected oocytes.
      The Xenopus H2B gene has a relatively simple promoter containing several
      transcriptional regulatory elements, including TFIID, CBP, and ATF/CREB binding
      sites, required for maximal transcription. A sequence (CTTTACAT) in the H2B
      promoter resembling the conserved octamer motif (ATTTGCAT), the target for cell
      cycle regulation of a human H2B gene, is not required for transcription in
      oocytes. Nonetheless, substitution of a consensus octamer motif for the variant
      octamer element activates H2B transcription. Oocyte factors, presumably including
      the ubiquitous Oct-1 factor, specifically bind to the consensus octamer motif but
      not to the variant sequence. Our results demonstrate that a transcriptional
      regulatory element involved in lymphoid-specific expression of immunoglobulin
      genes and in S-phase-specific activation of mammalian H2B histone genes can
      activate transcription in nondividing amphibian oocytes.

PMID- 1990277
TI  - Transcription complex disruption caused by a transition in chromatin structure.
AB  - Chromatin structure is known to influence class III gene expression in vitro. We
      describe the active transcription of Xenopus class III genes following
      replication and assembly into chromatin by using Xenopus egg extracts. Changes in
      the structure of this active chromatin dependent on the presence of exogeneous
      Mg2+ ATP or on the addition of a mixture of histones H2A and H2B are shown to
      lead to the selective repression of Xenopus 5S RNA genes. Preexisting
      transcription complexes on 5S DNA are disrupted following the reorganization of a
      "disordered" histone-DNA complex into a structure consisting of physiologically
      spaced nucleosomes. Thus, we demonstrate that chromatin structural transitions
      can have dominant and specific effects on transcription.

PMID- 1990278
TI  - Characterization of RPR1, an essential gene encoding the RNA component of
      Saccharomyces cerevisiae nuclear RNase P.
AB  - RNA components have been identified in preparations of RNase P from a number of
      eucaryotic sources, but final proof that these RNAs are true RNase P subunits has
      been elusive because the eucaryotic RNAs, unlike the procaryotic RNase P
      ribozymes, have not been shown to have catalytic activity in the absence of
      protein. We previously identified such an RNA component in Saccharomyces
      cerevisiae nuclear RNase P preparations and have now characterized the
      corresponding, chromosomal gene, called RPR1 (RNase P ribonucleoprotein 1). Gene
      disruption experiments showed RPR1 to be single copy and essential.
      Characterization of the gene region located RPR1 600 bp downstream of the URA3
      coding region on chromosome V. We have sequenced 400 bp upstream and 550 bp
      downstream of the region encoding the major 369-nucleotide RPR1 RNA. The presence
      of less abundant, potential precursor RNAs with an extra 84 nucleotides of 5'
      leader and up to 30 nucleotides of 3' trailing sequences suggests that the
      primary RPR1 transcript is subjected to multiple processing steps to obtain the
      369-nucleotide form. Complementation of RPR1-disrupted haploids with one variant
      of RPR1 gave a slow-growth and temperature-sensitive phenotype. This strain
      accumulates tRNA precursors that lack the 5' end maturation performed by RNase P,
      providing direct evidence that RPR1 RNA is an essential component of this enzyme.

PMID- 1990279
TI  - Constitutively expressed c-myb abrogates the requirement for insulinlike growth
      factor 1 in 3T3 fibroblasts.
AB  - The proto-oncogene c-myb, whose expression is usually limited to cells of the
      hematopoietic lineages, can be expressed in fibroblasts if placed under the
      control of a constitutive promoter, such as the simian virus SV40 early promoter.
      3T3 cells carrying a constitutively expressed human c-myb were found to grow in
      1% serum or in a serum-free, platelet-derived growth factor-supplemented medium,
      whereas the parent cell line, BALB/c 3T3, needed insulinlike growth factor 1 (IGF
      1) in addition to platelet-derived growth factor for growth. myb-carrying cells,
      however, could not grow in platelet-poor plasma. In fibroblasts, therefore, a
      constitutively expressed c-myb can abrogate the requirement for platelet-poor
      plasma or IGF-1. When 3T3 cells constitutively expressed both c-myc and c-myb,
      they could grow in serum-free medium without added growth factors. The ability of
      c-myb to abrogate in fibroblasts the IGF-1 requirement seems to be due to its
      ability to induce overexpression of IGF-1, as indicated by an increase in steady
      state levels of IGF-1 mRNA. These results have some important implications; for
      instance, they suggest a commonality of pathways for entry into S phase in
      different cell types and the possibility of a myb-like or myb-equivalent gene
      product of critical importance for entry of fibroblasts into S phase.

PMID- 1990280
TI  - Repair of specific base pair mismatches formed during meiotic recombination in
      the yeast Saccharomyces cerevisiae.
AB  - Heteroduplexes formed between DNA strands derived from different homologous
      chromosomes are an intermediate in meiotic crossing over in the yeast
      Saccharomyces cerevisiae and other eucaryotes. A heteroduplex formed between wild
      type and mutant genes will contain a base pair mismatch; failure to repair this
      mismatch will lead to postmeiotic segregation (PMS). By analyzing the frequency
      of PMS for various mutant alleles in the yeast HIS4 gene, we showed that C/C
      mismatches were inefficiently repaired relative to all other point mismatches.
      These other mismatches (G/G, G/A, T/T, A/A, T/C, C/A, A/A, and T/G) were repaired
      with approximately the same efficiency. We found that in spores with unrepaired
      mismatches in heteroduplexes, the nontranscribed strand of the HIS4 gene was more
      frequently donated than the transcribed strand. In addition, the direction of
      repair for certain mismatches was nonrandom.

PMID- 1990281
TI  - Suppressor analysis of temperature-sensitive mutations of the largest subunit of
      RNA polymerase I in Saccharomyces cerevisiae: a suppressor gene encodes the
      second-largest subunit of RNA polymerase I.
AB  - The SRP3-1 mutation is an allele-specific suppressor of temperature-sensitive
      mutations in the largest subunit (A190) of RNA polymerase I from Saccharomyces
      cerevisiae. Two mutations known to be suppressed by SRP3-1 are in the putative
      zinc-binding domain of A190. We have cloned the SRP3 gene by using its suppressor
      activity and determined its complete nucleotide sequence. We conclude from the
      following evidence that the SRP3 gene encodes the second-largest subunit (A135)
      of RNA polymerase I. First, the deduced amino acid sequence of the gene product
      contains several regions with high homology to the corresponding regions of the
      second-largest subunits of RNA polymerases of various origins, including those of
      RNA polymerase II and III from S. cerevisiae. Second, the deduced amino acid
      sequence contains known amino acid sequences of two tryptic peptides from the
      A135 subunit of RNA polymerase I purified from S. cerevisiae. Finally, a strain
      was constructed in which transcription of the SRP3 gene was controlled by the
      inducible GAL7 promoter. When this strain, which can grow on galactose but not on
      glucose, was shifted from galactose medium to glucose medium, a large decrease in
      the cellular concentration of A135 was observed by Western blot analysis. We have
      also identified the specific amino acid alteration responsible for suppression by
      SRP3-1 and found that it is located within the putative zinc-binding domain
      conserved among the second-largest subunits of eucaryotic RNA polymerases. From
      these results, it is suggested that this putative zinc-binding domain is in
      physical proximity to and interacts with the putative zinc-binding domain of the
      A190 subunit.

PMID- 1990282
TI  - Extracellular signals that regulate liver transcription factors during hepatic
      differentiation in vitro.
AB  - A complex cell culture environment has been shown to maintain the differentiated
      state of hepatocytes, yet the mechanisms by which environmental cues selectively
      maintain liver-specific gene transcription have been unknown. In this paper we
      show that the hepatic environment regulates the activities of at least three
      liver-enriched transcription factors, eE-TF, eG-TF/HNF3, and eH-TF, that activate
      the mouse serum albumin enhancer. eE-TF is a heat-stable factor that has a DNA
      binding specificity similar to that of the liver transcription factor C/EBP, but
      is a distinct protein. eG-TF/HNF3 contributes to the liver-specific transcription
      of several other serum protein genes. eH-TF binds to a TGTTTGC sequence that
      occurs at regulatory sites of the albumin promoter, the hepatitis B virus
      enhancer, and other hepatic genes. eE-TF, eG-TF/HNF3, and eH-TF are regulated by
      different combinations of the following cell culture conditions: a hormonally
      defined serum-free medium; an extracellular matrix gel; and a transformation
      competent simian virus 40 large T antigen. We propose a regulatory network model
      to explain how cues from the cell lineage and the extracellular environment
      coordinately help maintain the activities of transcription factors involved in
      hepatocyte differentiation.

PMID- 1990283
TI  - Specific cis-acting sequence for PHO8 expression interacts with PHO4 protein, a
      positive regulatory factor, in Saccharomyces cerevisiae.
AB  - The PHO8 gene of Saccharomyces cerevisiae encodes repressible alkaline
      phosphatase (rALPase; EC 3.1.3.1). The rALPase activity of the cells is two to
      three times higher in medium containing a low concentration of Pi than in high-Pi
      medium due to transcription of PHO8. The Pi signals are conveyed to PHO8 by
      binding of PHO4 protein, a positive regulatory factor, to a promoter region of
      PHO8 (PHO8p) under the influence of the PHO regulatory circuit. Deletion analysis
      of PHO8p DNA revealed two separate regulatory regions required for derepression
      of rALPase located at nucleotide positions -704 to -661 (distal region) and -548
      to -502 (proximal region) and an inhibitory region located at -421 to -289
      relative to the translation initiation codon. Gel retardation experiments showed
      that a beta-galactosidase-PHO4 fusion protein binds to a 132-bp PHO8p fragment
      bearing the proximal region but not to a 226-bp PHO8 DNA bearing the distal
      region. The fusion protein also binds to a synthetic oligonucleotide having the
      same 12-bp nucleotide sequence as the PHO8p DNA from positions -536 to -525. The
      132-bp PHO8p fragment, connected at position -281 of the 5' upstream region of a
      HIS5'-'lacZ fused gene, could sense Pi signals in vivo, but a 20-bp synthetic
      oligonucleotide having the same sequence from -544 to -525 of the PHO8p DNA could
      not. Linker insertions in the PHO8p DNA indicated that the 5-bp sequence 5'-CACGT
      3' from positions -535 to -531 is essential for binding the beta-galactosidase
      PHO4 fusion protein and for derepression of rALPase.

PMID- 1990284
TI  - Molecular cloning and functional characterization of the pathway-specific
      regulatory gene nirA, which controls nitrate assimilation in Aspergillus
      nidulans.
AB  - We have cloned an 11-kbp segment of the genomic DNA of Aspergillus nidulans which
      complements mutations in nirA, the pathway-specific regulatory gene of the
      nitrate assimilation pathway. Gene disruption in the corresponding region of the
      nuclear DNA leads to a phenotype and a gene complementation pattern
      indistinguishable from that observed in known noninducible nirA mutants.
      Transformation studies with subclones of the 11-kbp genomic segment showed that a
      nonreverting null mutation nirA87, maps to a 1.5-kbp stretch within that segment.
      These data confirm that the cloned segment contains the nirA gene. The gene is
      completely encompassed in the 11-kbp genomic segment, as a plasmid carrying the
      corresponding insert gives rise to multicopy transformants exhibiting better
      growth than wild type on nitrate or nitrite as the sole nitrogen source. Southern
      and genetic analyses of transformants obtained with various plasmid subclones
      established a gene size of at most 5.9 kbp. Northern (RNA) hybridization
      experiments revealed a 4-kb nirA transcript which is barely visible in the wild
      type but clearly seen in a transformant carrying about 10 gene copies. In both
      strains, nirA mRNA is synthesized constitutively. Upstream of nirA, a neighboring
      transcript about 2.8 kbp in length which is transcribed from the opposite strand
      with respect to nirA was localized. The transcript levels of niaD and niiA,
      encoding the nitrate and nitrite reductase core proteins, respectively, were
      investigated in nirA mutants and a nirA multicopy transformant. The results show
      that the nirA product regulates the transcript steady-state level of these
      structural genes and that it is a limiting factor for their expression.

PMID- 1990285
TI  - Yeast CBP1 mRNA 3' end formation is regulated during the induction of
      mitochondrial function.
AB  - Alternative mRNA processing is one mechanism for generating two or more
      polypeptides from a single gene. While many mammalian genes contain multiple mRNA
      3' cleavage and polyadenylation signals that change the coding sequence of the
      mature mRNA when used at different developmental stages or in different tissues,
      only one yeast gene has been identified with this capacity. The Saccharomyces
      cerevisiae nuclear gene CPB1 encodes a mitochondrial protein that is required for
      cytochrome b mRNA stability. This 66-kDa protein is encoded by a 2.2-kb mRNA
      transcribed from CPB1. Previously we showed that a second 1.2-kb transcript is
      initiated at the CBP1 promoter but has a 3' end near the middle of the coding
      sequence. Furthermore, it was shown that the ratio of the steady-state level of
      2.2-kb CBP1 message to 1.2-kb message decreases 10-fold during the induction of
      mitochondrial function, while the combined levels of both messages remain
      constant. Having proposed that regulation of 3' end formation dictates the amount
      of each CBP1 transcript, we now show that a 146-bp fragment from the middle of
      CBP1 is sufficient to direct carbon source-regulated production of two
      transcripts when inserted into the yeast URA3 gene. This fragment contains seven
      polyadenylation sites for the wild-type 1.2-kb mRNA, as mapped by sequence
      analysis of CBP1 cDNA clones. Deletion mutations upstream of the polyadenylation
      sites abolished formation of the 1.2-kb transcript, whereas deletion of three of
      the sites only led to a reduction in abundance of the 1.2-kb mRNA. Our results
      indicate that regulation of the abundance of both CBP1 transcripts is controlled
      by elements in a short segment of the gene that directs 3' end formation of the
      1.2-kb transcript, a unique case in yeast cells.

PMID- 1990286
TI  - The URE2 gene product of Saccharomyces cerevisiae plays an important role in the
      cellular response to the nitrogen source and has homology to glutathione s
      transferases.
AB  - The URE2 gene of Saccharomyces cerevisiae has been cloned and sequenced. It
      encodes a predicted polypeptide of 354 amino acids with a molecular weight of
      40,226. Deletion of the first 63 amino acids does not have any effect on the
      function of the protein. Studies with disruption alleles of the URE2 and GLN3
      genes showed that both genes regulate GLN1 and GDH2, the structural genes for
      glutamine synthetase and NAD-linked glutamate dehydrogenase, respectively, at the
      transcriptional level, but expression of the regulatory genes does not appear to
      be regulated. Active URE2 gene product was required for the inactivation of
      glutamine synthetase upon addition of glutamine to cells growing with glutamate
      as the source of nitrogen. The predicted URE2 gene product has homology to
      glutathione S-transferases. The gene has been mapped to chromosome XIV, 5.9 map
      units from petX and 3.4 map units from kex2.

PMID- 1990287
TI  - trans-Activation of a globin promoter in nonerythroid cells.
AB  - We show that expression in fibroblasts of a single cDNA, encoding the erythroid
      DNA-binding protein Eryf1 (GF-1, NF-E1), very efficiently activates transcription
      of a chicken alpha-globin promoter, trans-Activation in these cells occurred when
      Eryf1 bound to a single site within a minimal globin promoter. In contrast,
      efficient activation in erythroid cells required multiple Eryf1 binding sites.
      Our results indicate that mechanisms exist that are capable of modulating the
      trans-acting capabilities of Eryf1 in a cell-specific manner, without affecting
      DNA binding. The response of the minimal globin promoter to Eryf1 in fibroblasts
      was at least as great as for optimal constructions in erythroid cells. Therefore,
      the assay provides a very simple and sensitive system with which to study gene
      activation by a tissue-specific factor.

PMID- 1990288
TI  - Hyperexpression of interleukin-7 is not necessary or sufficient for
      transformation of a pre-B lymphoid cell line.
AB  - Interleukin-7 (IL-7) is a potent stimulator of pre-B-lymphocyte proliferation.
      Pre-B cells transformed by a variety of oncogenes including those of the ABL
      protein tyrosine kinase family were screened for endogenous IL-7 mRNA expression
      by polymerase chain reaction and a sensitive bioassay for secreted IL-7. Some v
      abl but none of the BCR/ABL, v-src, v-fms, v-myc, v-ras, or v-raf transformants
      analyzed contained elevated IL-7 transcripts. None of the cell lines secreted
      detectable bioactivity. We overexpressed IL-7 via a retroviral vector in an IL-7
      dependent pre-B cell line to assess the potential for autocrine growth
      stimulation and malignant transformation. We achieved dramatic deregulation of IL
      7 translational suppression by removing portions of the 5' flanking region.
      Levels of IL-7 expression much greater than those needed to establish factor
      independent growth did not induce colony formation in agar by IL-7-expressing pre
      B cell lines, and the majority of these lines were nontumorigenic in syngeneic
      mice. The same pre-B cell line transformed by v-abl displayed a highly malignant
      phenotype while containing dramatically lower IL-7 transcript levels. We conclude
      that endogenous IL-7 expression is not a necessary event in transformation of pre
      B cells, nor is it sufficient to explain the malignant phenotype in v-abl
      transformed cells. Up regulation of endogenous IL-7 expression in some
      transformed pre-B cells may be one of several synergistic events which can lead
      to malignant conversion.

PMID- 1990289
TI  - The core proteins A2 and B1 exist as (A2)3B1 tetramers in 40S nuclear
      ribonucleoprotein particles.
AB  - The six "core" proteins of HeLa cell 40S nuclear ribonucleoprotein particles
      (hnRNP particles) package 700-nucleotide lengths of pre-mRNA into a repeating
      array of regular particles. We have previously shown that the C proteins exist as
      anisotropic tetramers of (C1)3C2 in 40S hnRNP particles and that each particle
      probably contains three such tetramers. We report here that proteins A2 and B1
      also exist in monoparticles as (A2)3B1 tetramers and that each monoparticle
      contains at least three such tetramers. Proteins A2 and B1 dissociate from
      isolated monoparticles as a stable tetramer upon nuclease digestion. In low-salt
      gradients, the tetramers sediment at 6.8S, which is consistent with a mass of 145
      kDa. In 200 mM salt, the concentration which dissociates these proteins from RNA,
      only 4.2S dimers exist in solution. Tetramers of (A2)3B1 possess the ability to
      package multiples of 700 nucleotides of RNA in vitro into an array of regular,
      22.5-nm 43S particles. Unlike the in vitro assembly of intact 40S hnRNP, the
      (A2)3B1 tetramers assemble by means of a highly cooperative process. These
      findings indicate that the (A2)3B1 tetramers play a major role in hnRNP assembly
      and they further support the contention that 40S monoparticles are regular
      structures composed of three copies of three different tetramers, i.e.,
      3[(A1)3B2, (A2)3B1, (C1)3C2].

PMID- 1990291
TI  - Epidermal growth factor (EGF) stimulates association and kinase activity of Raf-1
      with the EGF receptor.
AB  - Raf-1 serine- and threonine-specific protein kinase is transiently activated in
      cells expressing the epidermal growth factor (EGF) receptor upon treatment with
      EGF. The stimulated EGF receptor coimmunoprecipitates with Raf-1 kinase and
      mediates protein kinase C-independent phosphorylation of Raf-1 on serine
      residues. Hyperphosphorylated Raf-1 has lower mobility on sodium dodecyl sulfate
      gels and has sixfold-increased activity in immunocomplex kinase assay with
      histone H1 or Raf-1 sequence-derived peptide as a substrate. Raf-1 activation
      requires kinase-active EGF receptor; a point mutant lacking tyrosine kinase
      activity in inactive in Raf-1 coupling and association. It is noteworthy that
      tyrosine phosphorylation of c-Raf-1 induced by EGF was not detected in these
      cells. These observations suggest that Raf-1 kinase may act as an important
      downstream effector of EGF signal transduction.

PMID- 1990290
TI  - Identification and structure of four yeast genes (SLY) that are able to suppress
      the functional loss of YPT1, a member of the RAS superfamily.
AB  - In Saccharomyces cerevisiae, the GTP-binding Ypt1 protein (Ypt1p) is essential
      for endoplasmic reticulum-to-Golgi protein transport. By exploiting a GAL10-YPT1
      fusion to regulate YPT1 expression, three multicopy suppressors, SLY2, SLY12, and
      SLY41, and a single-copy suppressor, SLY1-20, that allowed YPT1-independent
      growth were isolated. Wild-type Sly1p is hydrophilic, is essential for cell
      viability, and differs from Sly1-20p by a single amino acid. SLY2 and SLY12
      encode proteins with hydrophobic tails similar to synaptobrevins, integral
      membrane proteins of synaptic vesicles in higher eucaryotes. Sly41p is
      hydrophobic and exhibits sequence similarities with the chloroplast phosphate
      translocator. SLY12 but not SLY41 is an essential gene. The SLY2 null mutant is
      cold and heat sensitive. The SLY gene products may comprise elements of the
      protein transport machinery.

PMID- 1990292
TI  - Colony-stimulating factor 1 expression is down-regulated during the adipocyte
      differentiation of H-1/A marrow stromal cells and induced by cachectin/tumor
      necrosis factor.
AB  - We isolated clonal sublines of the established mouse marrow stromal cell line, H
      1. These clonal sublines underwent differentiation into adipocytes in various
      degrees. One subline, H-1/A, underwent adipocyte differentiation after
      confluence, while another subline, H-1/D, did not differentiate. In H-1/A cells,
      the 4.5- and 2.5-kb major mRNA species of colony-stimulating factor 1 (CSF-1)
      were expressed before differentiation and were down-regulated at a
      posttranscriptional level during the differentiation of H-1/A cells. The down
      regulation of the CSF-1 gene was not a result of arrested cellular growth,
      because no down-regulation was detected in the nondifferentiating sister line, H
      1/D. This down-regulation appeared to be an early event in differentiation.
      Cachectin/tumor necrosis factor transiently induced the expression of CSF-1 and
      inhibited the differentiation of H-1/A cells into adipocytes. This induced
      expression of CSF-1 was due to an increased rate of transcription.

PMID- 1990294
TI  - Structural and antigenic polymorphism of the 35- to 48-kilodalton merozoite
      surface antigen (MSA-2) of the malaria parasite Plasmodium falciparum.
AB  - Merozoite surface antigen MSA-2 of the human parasite Plasmodium falciparum is
      being considered for the development of a malaria vaccine. The antigen is
      polymorphic, and specific monoclonal antibodies differentiate five serological
      variants of MSA-2 among 25 parasite isolates. The variants are grouped into two
      major serogroups, A and B. Genes encoding two different variants from serogroup A
      have been sequenced, and their DNA together with deduced amino acid sequences
      were compared with sequences encoded by other alleles. The comparison shows that
      the serological classification reflects differences in DNA sequences and deduced
      primary structure of MSA-2 variants and serogroups. Thus, the overall homologies
      of DNA and amino acid sequences are over 95% among variants in the same
      serogroup. In contrast, similarities between the group A variants and a group B
      variant are only 70 and 64% for DNA and amino acid sequences, respectively. We
      propose that the MSA-2 protein is encoded by two highly divergent groups of
      alleles, with limited additional polymorphism displayed within each group.

PMID- 1990293
TI  - Intracellular leucine zipper interactions suggest c-Myc hetero-oligomerization.
AB  - The physiological significance of in vitro leucine zipper interactions was
      studied by the use of two strategies which detect specific protein-protein
      interactions in mammalian cells. Fusion genes were constructed which produce
      chimeric proteins containing leucine zipper domains from several proteins fused
      either to the DNA-binding domain of the Saccharomyces cerevisiae GAL4 protein or
      to the transcriptional activation domain of the herpes simplex virus VP16
      protein. Previous studies in mammalian cells have demonstrated that a single
      chimeric polypeptide containing these two domains will activate transcription of
      a reporter gene present downstream of the GAL4 DNA-binding site. Similarly, if
      the GAL4 DNA-binding domain of a chimeric protein could be complexed through
      leucine zipper interactions with the VP16 activation domain of another chimeric
      protein, then transcriptional activation of the reporter gene would be detected.
      Using this strategy for detecting leucine zipper interactions, we observed homo
      oligomerization between leucine zipper domains of the yeast protein GCN4 and
      hetero-oligomerization between leucine zipper regions from the mammalian
      transcriptional regulating proteins c-Jun and c-Fos. In contrast, homo
      oligomerization of the leucine zipper domain from c-Myc was not detectable in
      cells. The inability of the c-Myc leucine zipper to homo-oligomerize strongly in
      cells was confirmed independently. The second strategy to detect leucine zipper
      interactions takes advantage of the observation that the addition of nuclear
      localization sequences to a cytoplasmic protein will allow the cytoplasmic
      protein to be transported to and retained in the nucleus. Chimeric genes encoding
      proteins with sequences from a cytoplasmic protein fused either to the GCN4 or c
      Myc leucine zipper domains were constructed. Experiments with the c-Myc chimeric
      protein failed to demonstrate transport of the cytoplasmic marker protein to the
      nucleus in cells expressing the wild-type c-Myc protein. In contrast, the
      cytoplasmic marker was translocated into the nucleus when the GCN4 leucine
      zippers were present on both the cytoplasmic marker and a nuclear protein,
      presumably as a result of leucine zipper interaction. These results suggest that
      c-Myc function requires hetero-oligomerization to an as yet undefined factor.

PMID- 1990296
TI  - [Aging, fragmentation and responsibility].

PMID- 1990295
TI  - Control of junB and extracellular matrix protein expression by transforming
      growth factor-beta 1 is independent of simian virus 40 T antigen-sensitive growth
      sensitive growth-inhibitory events.
AB  - Treatment of Mv1Lu mink lung epithelial cells with transforming growth factor
      beta 1 (TGF-beta 1) prevents phosphorylation of the retinoblastoma susceptibility
      gene product, RB, in late G1 phase of the cell cycle, which is thought to retain
      RB in a growth-suppressive state. This effect is paralleled by cell cycle arrest
      in late G1 (M. Laiho, J. A. DeCapric, J. W. Ludlow, D. M. Livingston, and J.
      Massague, Cell 62:175-185, 1990). Arrest can be prevented by expression of simian
      virus 40 T antigen, which binds to underphosphorylated RB, presumably blocking
      its growth-suppressive activity. The response of cells to TGF-beta 1, however, is
      complex and includes changes in the levels of expression of genes encoding
      nuclear transcription factors and extracellular matrix components. To define the
      relationships among various components of the TGF-beta 1 response, we have
      investigated the effect of TGF-beta 1 on cells whose growth-inhibitory response
      to this factor is prevented by T antigen. TGF-beta 1 addition to exponentially
      growing Mv1Lu cells increased the levels of junB mRNA and of three extracellular
      matrix proteins: plasminogen activator inhibitor-1, fibronectin, and
      thrombospondin. Kinetically, the effects on junB and plasminogen activator
      inhibitor-1 expression occurred faster (half-maximal at 1 to 2 h) than the
      effects on fibronectin and thrombospondin expression (half-maximal at 6 to 10 h).
      These effects either preceded or overlapped, respectively, the withdrawal of
      Mv1Lu cells from the cell cycle. Expression of a transfected T-antigen gene in
      Mv1Lu cells, however, did not prevent any of these responses to TGF-beta 1. The
      results indcate that TGF-B1-stimulated expression of junB and extracellular
      matrix proteins in Mv1Lu cells can occur independently of the T-antigen-sensitive
      events that lead to growth arrest.

PMID- 1990297
TI  - [Haemophilus influenzae type b infections in children].

PMID- 1990298
TI  - [The treatable cause of cough-induced headache].

PMID- 1990299
TI  - [Acrodermatitis enteropathica; a literature review].
AB  - A young girl with recurrent upper respiratory tract infection showed minor skin
      lesions and was found to suffer from acrodermatitis enteropathica. She responded
      dramatically to treatment with zinc sulphate. We review the signs and symptoms
      and their reported frequencies in 196 reported patients. The classical triad,
      dermatitis, alopecia and intractable diarrhoea is present in only 20% of the
      cases. Their intermittent occurrence and the vast range of other, also misleading
      symptoms, may cause a diagnostic problem. Treatment is effective, safe and
      simple: 3 to 30 mumol zinc per kg per day. Attention should be paid to sorbitol,
      added to the standard Dutch zinc sulphate prescription. It may induce diarrhoea.

PMID- 1990301
TI  - [Small intestine perforation as a complication of treatment with loperamide in a
      Salmonella typhimurium infection].

PMID- 1990300
TI  - [Pneumocystis carinii pneumonia in patients with a severe combined
      immunodeficiency].
AB  - We describe three patients with Pneumocystis carinii pneumonia as the initial
      presentation of severe combined immunodeficiency disease. The pneumonia in the
      first patient was treated successfully with trimethoprim/sulphamethoxazole
      (Tmp/Smz). The second patient died despite therapy with Tmp/Smz and pentamidine.
      The third patient failed to respond to therapy with Tmp/Smz and pentamidine. He
      was subsequently treated with trimetrexate and leucovorin. Treatment with the new
      folic acid antagonist trimetrexate resulted in complete recovery. The case
      histories of these children serve to illustrate the clinical symptoms and new
      therapeutic modalities of P. carinii pneumonia in patients with immunodeficiency
      disease.

PMID- 1990303
TI  - [Osteogenesis imperfecta; more than only many fractures].

PMID- 1990302
TI  - [Breast carcinoma following primary augmentation plasty of the breast].

PMID- 1990304
TI  - [Epidemiology of Haemophilus influenzae type b infections in The Netherlands and
      elsewhere].

PMID- 1990305
TI  - [Giant cell arteritis: more than just temporal arteritis].

PMID- 1990306
TI  - [Prevention of gastroduodenal disorders with the use of non-steroidal anti
      inflammatory drugs].

PMID- 1990307
TI  - [Food allergy. I. Definition; other undesirable reactions to food; the mucosal
      gastrointestinal barrier].

PMID- 1990308
TI  - [Food allergy. II. Non-optimal function of the mucosal gastrointestinal barrier;
      types of allergic reactions; symptoms, diagnosis and treatment].

PMID- 1990309
TI  - [Food additives and hyperactivity in children].

PMID- 1990310
TI  - [Diagnosis and prognosis of polymyalgia rheumatica and giant cell arteritis].
AB  - Retrospectively the data were examined of 69 patients with polymyalgia rheumatica
      (PMR) and giant-cell arteritis (GCA), of whom 62 were treated with
      corticosteroids. The clinical and laboratory data, and the outcome of temporal
      artery biopsy were compared. In addition the relation between the course of the
      disease and survival was investigated. PMR and GCA are closely related syndromes
      with a multiform clinical presentation. There even is a group of patients with
      merely systemic symptoms, without specific signs of PMR or GCA. Concerning the
      course of the disease patients can be divided into groups with a shorter and
      longer period of disease activity; patients with a smooth stable remission and a
      chronic disease. The former group shows a significantly better five-year
      survival. At the time of diagnosis no reliable prediction of the course of the
      disease is possible.

PMID- 1990311
TI  - [Utilization of food supplements in The Netherlands].
AB  - In 1987 and 1988 a dietary survey was carried out in a representative sample of
      the Dutch population, under the authority of the Ministries of Welfare, Health
      and Cultural Affairs, and Agriculture and Fisheries. By means of a two day
      dietary record data were collected on food consumption and the use of dietary
      supplements. More than seventeen percent of the Dutch population has been using
      at least one dietary supplement on at least one day of the survey. Age, sex,
      season, social class, alternative food habits, smoking and diet are related to
      the use of supplements. In young persons mainly fluoride and vitamin AD
      preparations are used, while as age progresses a shift towards other supplements,
      like garlic and brewer's yeast preparations, is observed. The use of single
      vitamin C supplements is not related to the level of mean daily vitamin C intake
      from foods.

PMID- 1990312
TI  - [2 newborn infants with septicemia caused by multiresistant Streptococcus mitis].
AB  - Multiresistant viridans streptococci had not yet been encountered in the
      Netherlands. In the spring of 1990 we isolated multiresistant S. mitis from blood
      of two Dutch neonates (minimal inhibitory concentration of penicillin 64 mg/l).
      In both patients septicaemia developed while they were being treated with beta
      lactam antibiotics. Although viridans streptococci usually are extremely
      sensitive to penicillin and other beta-lactams, the possibility of development of
      (multi-)resistance in these microorganisms during antibiotic treatment should be
      kept in mind.

PMID- 1990314
TI  - 43rd annual meeting: American Academy of Neurology. Abstract listing and general
      meeting information. April 21-27, 1991.

PMID- 1990313
TI  - [Sour fruits of old age; malnutrition in advanced age].

PMID- 1990315
TI  - Social support in student nurse clinical groups.

PMID- 1990317
TI  - Using unfamiliar clinical settings for RN students.
AB  - In light of this experience, I encourage faculty members to help their RN
      students realize the value in an unfamiliar practice setting. Not only does it
      provide new knowledge and insights, but it also encourages the application of
      prior knowledge to new, unfamiliar settings in order to find solutions and
      implement new strategies. Personal creativity is enhanced as the nursing process
      is implemented.

PMID- 1990316
TI  - Campus wellness vacation: a creative clinical experience with the elderly.
AB  - A campus wellness vacation for healthy elderly persons was established to provide
      RN students with an innovative way to observe healthy aging. The author discusses
      this creative experience: what it was; how it was planned and implemented; how it
      related to course requirements; how it changed over the years. Suggestions are
      given for faculty who want to try a similar program.

PMID- 1990318
TI  - A participatory learning module: asepsis and universal precautions.
AB  - Mastery of medical and surgical asepsis principles is mandatory for nurses in
      today's health care environment. The authors report on the development,
      implementation, and evaluation of a multimedia asepsis module incorporating
      universal precautions. Practical application of the content, using graphics,
      medical supplies, and video, occurs in the four-station participatory learning
      module. Student evaluations of this learning module are positive.

PMID- 1990319
TI  - Report cards: a preparation strategy for NCLEX-RN.
AB  - Helping students to prepare for NCLEX-RN is a challenge for educators. One school
      designed a report card method that motivated the students to become involved in
      their own review. This strategy allowed the student to mastermind a plan with
      just a little help from a faculty advisor. The overall student compliance rate
      with these strategies was 68%. The authors discuss the how-to's of the report
      card method and the resources needed. The authors believe the report card
      strategy was the major contributing factor to their school's drastic increase in
      NCLEX-RN scores.

PMID- 1990320
TI  - Five strategies to use with beginning students.

PMID- 1990321
TI  - A guide to the accreditation process.
AB  - The accreditation process is comprehensive, time-consuming, and often anxiety
      producing. However, this process of peer review identifies areas of excellence as
      well as those requiring additional attention. Accreditation is a process in which
      the nursing profession excels and of which we can be proud.

PMID- 1990322
TI  - Microteaching: developing tomorrow's teachers.
AB  - Microteaching is a technique for developing teaching skills. The authors report a
      study that assessed graduate students' perspectives of a microteaching
      experience. Information is provided to help current and potential faculty members
      to improve their teaching skills through microteaching.

PMID- 1990323
TI  - Using alumni associations effectively.
AB  - The purpose of alumni associations is to foster relationships with their schools'
      graduates. The author describes how an active alumni association can meet the
      needs of nursing schools and their graduates by increasing revenues and student
      recruitment, providing opportunities to network, and disseminating information.
      Examples of alumni activities that meet these goals and foster commitment to the
      school are discussed.

PMID- 1990324
TI  - Cheat sheets.

PMID- 1990325
TI  - The creative teacher.
AB  - The challenge to adequately prepare students for the increasingly diverse
      profession of nursing is great. Due to a more heterogeneous population of nursing
      students, educators have to be more flexible in their approaches to education. As
      a result, educators are searching for more creative approaches to teaching. The
      authors examined what makes teaching creative. They identified creative nursing
      educators and examined their common approaches and strategies.

PMID- 1990326
TI  - A test protocol for large groups.
AB  - An effective and time-saving test protocol is presented for nurse educators who
      must cope with evaluating the progress of large numbers of students. Processes
      for the administration of tests to large groups are explained, and advantages and
      disadvantages are explored. The protocol may be used successfully with the
      expectation of greater ease and flexibility for nurse educators and reduced
      anxiety and frustration for students.

PMID- 1990327
TI  - Law for the nurse manager. QA and risk management: reducing liability exposure.

PMID- 1990328
TI  - The art of management. Empowering staff nurses: decision on the action level.

PMID- 1990329
TI  - Adopting a nursing minimum data set.

PMID- 1990330
TI  - Legislative effects: what's next? $40 million for nursing research: is it enough?

PMID- 1990331
TI  - Motivation strategies: a new twist.

PMID- 1990332
TI  - Feedback and efficiency: a staff development model.

PMID- 1990333
TI  - Verbal abuse nationwide, Part I: Oppressed group behavior.

PMID- 1990334
TI  - Acute care for the elderly: a new approach.

PMID- 1990336
TI  - An in-house registry: a pragmatic approach that works!

PMID- 1990335
TI  - Twelve-hour shifts on a new telemetry unit.

PMID- 1990337
TI  - A word about clinical privileging.

PMID- 1990338
TI  - Role of the clinical nurse specialist in open heart surgery.

PMID- 1990340
TI  - Preparing for surgery: a pre-admission testing and teaching unit.

PMID- 1990339
TI  - The ethics of limiting treatment: DNR decisions.

PMID- 1990341
TI  - Using hospital volunteers in a quality assurance program.

PMID- 1990342
TI  - Encounters: first impressions are lasting ones.

PMID- 1990343
TI  - . . . of alligators, ants and fireflies.

PMID- 1990344
TI  - Head nurses help insure consistent care.

PMID- 1990345
TI  - Chronic fatigue syndrome definition sparks off debate.

PMID- 1990346
TI  - Bringing hope.

PMID- 1990347
TI  - Judging misconduct. Interview by Claire Laurent.

PMID- 1990349
TI  - Private indemnity.

PMID- 1990348
TI  - Rough justice.

PMID- 1990350
TI  - Accountability. Stand up and be counted.

PMID- 1990351
TI  - Accountability. When to sound an alarm.

PMID- 1990352
TI  - Practising preachers.

PMID- 1990353
TI  - Home and dry.

PMID- 1990354
TI  - Whose problem?

PMID- 1990357
TI  - Preserving dignity through care. Care study.

PMID- 1990356
TI  - Getting ready to retire.

PMID- 1990355
TI  - Retirement. Life after work.

PMID- 1990358
TI  - Support for newly registered staff.

PMID- 1990360
TI  - Student nurses' pain assessment of children.

PMID- 1990359
TI  - Case study of management changes in the NHS.

PMID- 1990361
TI  - Community Health. All change ahead.

PMID- 1990362
TI  - Screening the elderly.

PMID- 1990363
TI  - Croydon community trust.

PMID- 1990364
TI  - RCN critical of surgeons' HIV testing guidelines.

PMID- 1990365
TI  - Birth of discontent.

PMID- 1990366
TI  - Gulf war. Ready and waiting.

PMID- 1990367
TI  - Gulf war. A moral dilemma.

PMID- 1990368
TI  - Off beam.

PMID- 1990369
TI  - State of the union.

PMID- 1990370
TI  - Charitable concern.

PMID- 1990371
TI  - Substance abuse. A misuse of ability.

PMID- 1990372
TI  - Substance abuse. The dracpackers.

PMID- 1990373
TI  - Assessing rheumatic disease.

PMID- 1990374
TI  - Fight for life.

PMID- 1990375
TI  - Open learning. High profiles.

PMID- 1990376
TI  - Open learning. Snakes and ladders. Interview by Laura Swaffield.

PMID- 1990377
TI  - Operating in Canada.

PMID- 1990378
TI  - Angels of death?

PMID- 1990379
TI  - Meaningful dialogue.

PMID- 1990380
TI  - Back on course.

PMID- 1990381
TI  - The use of section 5(4) to detain patients.

PMID- 1990382
TI  - Primary nursing. Night-time associates.

PMID- 1990383
TI  - Primary nursing. Intensive disagreement.

PMID- 1990384
TI  - Drugs to lower uric acid levels. How to avoid misuse in gouty arthritis.
AB  - Several points regarding the use of drugs to lower uric acid levels deserve
      emphasis. First, these agents are not useful in the management of acute gout.
      Second, all forms of the drugs should be initiated at low dose with gradual
      increments to achieve a serum uric acid level between 5 and 6 mg/dL. There are no
      data to support the widely presumed notion that dropping the uric acid level to a
      very low range (1 to 3 mg/dL) hastens resorption of tophi or improves joint
      function. Third, the uricosuric agents probenecid (Benemid) and sulfinpyrazone
      (Anturane) interact with a number of drugs, and both the patient and physician
      should be aware of this. Finally, and most important, careful and frequent
      monitoring is needed during the first several months of therapy with these drugs.

PMID- 1990385
TI  - Gallstone pancreatitis. Choosing and timing treatment.
AB  - Patients with gallstone pancreatitis are often seen initially by primary care
      physicians. Prompt diagnosis and timely intervention are crucial in reducing
      morbidity and mortality. Initial management should include supportive medical
      care and surgical consultation. The timing of surgery is then dictated by serum
      enzyme levels and liver function test results as well as by the patient's
      condition. The role of endoscopic intervention is currently evolving. Whether
      surgery or endoscopic sphincterotomy is preferable as primary therapy for
      gallstone pancreatitis remains unresolved. However, sphincterotomy with stone
      extraction is a viable option in selected cases, especially in patients who have
      severe gallstone pancreatitis.

PMID- 1990386
TI  - Sexually transmitted viral disease in women.
AB  - During the past decade, the incidence of sexually transmitted viral diseases has
      increased dramatically. In many cases, diagnosis is difficult, consequences are
      severe, and curative therapy is not available at present. In this article, Drs
      Peaceman and Gonik review current evidence about sexual transmission of viruses
      and discuss the latest methods of diagnosis, management, and prevention.

PMID- 1990388
TI  - Sign up to do lab tests--or else!

PMID- 1990387
TI  - Degenerative aortic stenosis. One effect of the graying of America.
AB  - Degenerative calcific aortic stenosis is evolving as a common geriatric problem.
      Once symptoms develop, it is a highly lethal disease that does not respond well
      to medical therapy. Aortic balloon valvuloplasty may offer palliation but is
      unlikely to alter the overall course of the disease. Aortic valve replacement is
      the therapy of choice, but high perioperative morbidity and mortality rates can
      be expected in the very elderly. The presence of other appreciable cardiac
      disorders may contribute to the occurrence of postoperative complications.
      Patients with asymptomatic aortic stenosis and normal left ventricular function
      can be treated medically and followed with serial aortic valve area
      determinations using Doppler echocardiography.

PMID- 1990389
TI  - Blistering diseases. Diagnostic help for primary care physicians.
AB  - At presentation, the differential diagnosis of bullous disease may seem
      difficult. However, the diagnosis may be clarified by considering such factors as
      Nikolsky's sign, age of the patient at onset, and pattern and distribution of
      blisters. Careful review of family, recreational, occupational, and drug
      histories may also help to identify the cause.

PMID- 1990391
TI  - A three-point approach to anemia.
AB  - Anemia is a sign of underlying disease that is causing blood loss, sequestration
      of red blood cells (RBCs), impaired RBC production, or primary marrow
      dysfunction. The most efficient clinical approach to a patient with anemia is to
      ask the following three questions: Is the anemia microcytic, macrocytic, or
      normocytic? Is pancytopenia present? Is the marrow response appropriate for the
      anemia as determined by the reticulocyte count? Answers to these questions focus
      laboratory evaluation on a logical progression and avoid a costly shotgun
      approach.

PMID- 1990390
TI  - When is pulmonary artery catheterization worth the risks?
AB  - Bedside pulmonary artery catheterization has proven to be an important addition
      to the clinical assessment of critically ill patients. Properly used, the
      procedure may provide hemodynamic information that is not apparent from physical
      examination or radiography. It may be safely accomplished through various venous
      routes, but care must be taken to avoid potential complications.

PMID- 1990392
TI  - Gynecomastia. A bothersome but readily treatable problem.
AB  - Although breast enlargement in boys and men can cause both psychological and
      physical distress, the disorder is rarely serious and is readily treatable.
      Several factors can lead to the estrogenic excess that causes growth of breast
      tissue. Dr Jacobs describes a patient with gynecomastia related to cirrhosis of
      the liver who responded promptly to a brief course of tamoxifen citrate therapy.

PMID- 1990393
TI  - The latest fads to increase muscle mass and energy. A look at what some athletes
      are using.
AB  - How different fads get started in different parts of the country defies rational
      explanation. This holds true in the world of athletic competition. In one locale
      athletes may be taking ginseng to promote strength, while in another they may be
      taking antioxidants to recover quickly after exertion. As Dr Woolley explains,
      some of the substances used do have the desired effects, some appear to have
      little or no effect, and some have dangerous effects.

PMID- 1990394
TI  - Managing miscarriage. The need for more than medical mechanics.
AB  - A compassionate physician recognizes the emotional as well as the physical needs
      of a woman who miscarries. The physical trauma is often short-lived, but the
      emotional aftermath may be prolonged. Dr Wells reviews the differential diagnosis
      and management of miscarriage and discusses the valuable role that a physician
      may take in alleviating the patient's feelings of guilt, grief, and frustration.

PMID- 1990395
TI  - Doctor, Doctor strikes a nerve.

PMID- 1990396
TI  - Chronic fatigue syndrome: is it real?
AB  - Epstein-Barr virus is no longer considered an important cause of chronic fatigue
      syndrome. Instead, the disease is probably related to an underlying psychiatric
      disorder, subtle immunologic dysfunction, or an interaction between these two
      factors. A carefully taken history, physical examination, and simple laboratory
      testing are usually sufficient to establish the diagnosis. Therapy with
      antidepressants or nonsteroidal anti-inflammatory drugs may be effective in
      selected patients. Thorough follow-up conducted with empathy and optimism is
      important in all cases.

PMID- 1990397
TI  - Musculoskeletal abnormalities in a patient with juvenile hypothyroidism.
AB  - Abnormalities in growth and development are the most striking clinical features
      of juvenile acquired hypothyroidism. Therefore, physicians should consider the
      diagnosis of hypothyroidism in any child with musculoskeletal growth dysfunction.
      Drs Kilpatrick and Fincher describe a case demonstrating the severe and
      potentially irreversible effects of prolonged, untreated hypothyroidism.

PMID- 1990398
TI  - The bed-wetting child. Current management of a frustrating problem.
AB  - Bed-wetting is a frustrating problem experienced by a significant number of
      children. It is the role of the physician to exclude serious underlying problems
      and, at the same time, educate the family concerning treatment options that may
      be best suited to their child. Once parents and child have a better understanding
      of the problem and realize that the outlook for nighttime bladder control is
      excellent, it is easier to start long-term care.

PMID- 1990399
TI  - Rheumatoid arthritis. New developments in treatment.
AB  - If a patient with active rheumatoid arthritis does not obtain significant relief
      from nonsteroidal anti-inflammatory drugs, prompt institution of disease
      modifying antirheumatic drugs (DMARDs) is recommended. If one agent fails,
      another may be tried. At present, hydroxychloroquine (Plaquenil) sulfate is one
      of the most widely used and best tolerated. Careful follow-up is essential with
      all DMARDs, however, because toxic effects may be severe and sometimes
      unpredictable.

PMID- 1990400
TI  - Laboratory tests for rheumatic diseases.
AB  - A carefully taken history and thorough physical examination remain the most
      crucial aspects of diagnosing rheumatic disorders. Non-rheumatologic conditions
      also need to be kept in mind. Laboratory tests should be looked on as mostly
      supportive or confirmatory, because many of the tests are relatively nonspecific
      and may lack sensitivity. If their limitations are recognized, however, the tests
      can be invaluable tools when the clinician confronts the task of differentiating
      an array of rheumatologic disorders.

PMID- 1990401
TI  - Oxygen-reactive species and antioxidant responses during development: the
      metabolic paradox of cellular differentiation.
AB  - Metabolic gradients are established during early phases of development and their
      existence influences subsequent developmental events. Variations in oxygen supply
      and oxygen metabolism associated with the gradation of metabolic rate in embryos
      appear to form one basis for the influence of metabolic gradients on development.
      The rate of oxygen metabolism affects the rate of oxidant generation by various
      cellular biochemical pathways. Cells contain antioxidant defenses that respond to
      variations in cellular oxidant production. Large changes in the activity of the
      antioxidant enzyme superoxide dismutase and changes in cellular redox state occur
      during the differentiation of many types of cells. These changes correspond to an
      increased rate of oxidant production; the cellular environment becomes more
      prooxidizing during differentiation. Evidence is presented that implicates
      oxidants as a factor that can stimulate alterations in gene expression. Possible
      mechanisms by which oxidants influence gene expression are also discussed.

PMID- 1990402
TI  - Copper transport: an overview.

PMID- 1990403
TI  - The zona pellucida genes encode essential proteins for mammalian fertilization
      and early embryogenesis.

PMID- 1990404
TI  - Levels and 75Se-labeling of specific proteins as a consequence of dietary
      selenium concentration in mice and rats.
AB  - Selenium-labeled proteins (SLP) distinct from glutathione peroxidase (GSH-PX)
      recently have been purified and partially characterized. Antisera to two SLP, a
      56-kDa and a 14-kDa protein, were generated in rabbits and used to examine
      expression of these proteins as a consequence of dietary selenium concentration
      (0.02, 0.2, 2.0 ppm) in mice and rats. Additionally, the kinetics of 75Se
      labeling in plasma, liver, kidney, and mammary gland were examined over a 40-hr
      time period as a function of dietary selenium concentration. A plasma 57-kDa
      protein was labeled by 30 min after 75Se injection and reached maximum labeling
      by 4 hr. The cellular 56-kDa and 14-kDa proteins, as well as GSH-Px, labeled
      progressively over 40 hr starting between 1 and 4 hr after injection. In general,
      the 56-kDa and GSH-Px followed similar labeling patterns, whereas the 14-kDa
      protein was labeled less and was not labeled in discernible quantities until 40
      hr. The extent of labeling of all proteins was inversely proportional to the
      dietary selenium concentration and was probably a reflection of different
      endogenous selenium body pools. The most important observation was generated by
      the immunoblot data. The amount of 56-kDa and 14-kDa proteins as detected and
      measured on immunoblots was not a function of dietary selenium concentration.
      This result suggests that the synthesis and maintenance of the 56-kDa and 14-kDa
      proteins are not selenium dependent, a characteristic which distinguishes the two
      proteins from GSH-Px. The single exception to the above results was the 40%
      decrease of liver 14-kDa protein concentration in carcinogen-treated rats fed 2.0
      ppm of selenium. An organic selenium compound, selenobetaine, did not lead to a
      decrease under similar conditions. In 15 rat mammary tumors induced by 7,12
      dimethylbenzanthracene and analyzed on immunoblots, the SLP-56 was undetected in
      5 cases and appeared as two bands (56,000 Da, 50,000 Da) in 10 cases. This latter
      result raises the possibility that the expression of SLP-56 may be altered in
      mammary tumors as compared with normal mammary gland.

PMID- 1990406
TI  - Inhibition of posthemorrhagic transfusion-induced gastric injury by a long-acting
      superoxide dismutase derivative.
AB  - Although oxygen-free radicals have been postulated to play an important role in
      the pathogenesis of gastric mucosal injury induced by posthemorrhagic blood
      transfusion, direct evidence supporting this hypothesis is lacking. Superoxide
      dismutase (SOD) has been shown to inhibit oxygen toxicity in vitro in various
      types of cell injury. However, in some cases, oxidative tissue injury cannot be
      decreased efficiency predominantly due to its rapid elimination by renal
      glomerular filtration. To overcome such frustrating situations, we have
      synthesized a SOD derivative that circulates bound to albumin with a half-life of
      6 hr. When blood was withdrawn from the rat (22 ml/kg) for 30 min followed by
      transfusion of the extracted blood, marked gastric mucosal lesions occurred
      within 30 min after transfusion. Intravenously injected SOD derivative markedly
      decreased gastric mucosal injury. Kinetic analysis using 125I-labeled albumin
      revealed that the vascular permeability of the stomach increased significantly
      after transfusion by a SOD derivative inhibitable mechanism. Thus, superoxide
      radical and/or its metabolite(s) play a critical role in the pathogenesis of
      posthemorrhagic transfusion-induced gastric injury.

PMID- 1990405
TI  - Relationship of liver and skeletal muscle IGF-1 mRNA to plasma GH profile,
      production of IGF-1 by liver, plasma IGF-1 concentrations, and growth rates of
      cattle.
AB  - Growth hormone (GH), insulin-like growth factor-1 (IGF-1), and thyroid hormone
      (T3 and T4) concentrations in blood plasma of 18 crossbred cattle (six bulls, six
      steers, and six heifers) were measured over an 8-hr period. One week later at
      slaughter, IGF-1 production by liver slices and IGF-1 mRNA concentrations in
      skeletal muscle and liver were measured. Bulls had higher (P less than 0.05) mean
      plasma GH and GH peak amplitudes (P less than 0.01) than heifers, and values for
      steers were intermediate between bulls and heifers. Baseline GH concentrations
      and number of GH peaks were not significantly different for the three groups.
      Bulls had 1.6-fold (P less than 0.01) and 3.0-fold (P less than 0.01) greater
      liver IGF-1 mRNA concentrations than steers or heifers, respectively, whereas the
      steers had 1.8-fold (P less than 0.05) greater IGF-1 mRNA in liver than heifers.
      Production of IGF-1 by liver slices was greater (P less than 0.05) in bulls than
      steers or heifers. Bulls had 1.3-fold greater plasma IGF-1 than steers (P less
      than 0.01), whereas steers had 1.8-fold greater plasma IGF-1 than heifers (P less
      than 0.01). There were no significant differences in concentrations of skeletal
      muscle IGF-1 mRNA between the three groups of animals. Liver IGF-1 mRNA, liver
      IGF-1 production, and plasma IGF-1 were all significantly correlated with gain
      and mean GH peak amplitude, but not with GH baseline, GH peak frequency, or
      concentrations of T3 and T4. Concentrations if IGF-1 mRNA in skeletal muscle were
      not correlated to gain or any parameter of the GH profile. Plasma concentrations
      of T3 were significantly (P less than 0.05) negatively correlated to plasma GH
      baseline concentrations. Muscle IGF-1 mRNA concentration was negatively related
      to plasma T4 and T3. The results of this study suggest that the cascade of events
      starting with secretion of GH from the pituitary, expression of liver IGF-1 mRNA,
      and secretion of IGF-1 by the liver are important phenomena for growth of cattle.

PMID- 1990407
TI  - Enhanced glomerulopressin production and glomerular filtration rate by amino acid
      infusion in normal humans.
AB  - Amino acid infusion induces a rise in glomerular filtration rate (GFR) in normal
      subjects, but the mechanism is as yet unknown. Glomerulopressin infused into the
      renal arteries of rats and dogs increases GFR. The aim of this study was to
      ascertain whether amino acid infusion raised glomerulopressin production and GFR.
      Accordingly, before renal arteriovenography, in 11 potential kidney donors, the
      caval catheter was introduced into the right hepatic vein and 60-ml blood samples
      were collected at the beginning and end of each experiment; six patients received
      amino acid infusion and five a saline infusion. Glomerulopressin in
      ultrafiltrates from hepatic vein plasma was measured by toad bioassay and GFR
      determined with diethylenetriamine pentaacetic acid-Tc99. The amino acid-infused
      group showed significant glomerulopressin activity in ultrafiltrates, as well as
      a significant GFR increase, whereas in the control group no glomerulopressin
      activity was observed, and there was no change in GFR. These findings suggest
      that intravenous amino acid infusion stimulates glomerulopressin production,
      which may in turn induce an increase in GFR.

PMID- 1990408
TI  - Fluoride reabsorption by nonionic diffusion in the distal nephron of the dog.
AB  - This study was done to test the hypothesis that fluoride reabsorption is
      extensive from the distal nephron, the major site for tubular fluid
      acidification, and to compare the distal nephron handling of fluoride and
      chloride. Ten stop-flow studies were done in five dogs anesthetized with
      pentobarbital. Urinary alkalinization was achieved by the intravenous infusion of
      sodium bicarbonate and acetazolamide or lithium chloride. Acidification was
      achieved by the infusion of sodium nitrate or sodium sulfate. The results
      indicate that the extent of fluoride reabsorption from the distal nephron is
      inversely correlated with urinary pH (P less than 0.001). When the urine was
      strongly acidified by the infusion of sodium sulfate, urine to plasma fluoride
      concentration ratios were less than 1.0, a finding not previously reported from
      studies of the renal handling of fluoride. The reabsorption of fluoride from the
      distal nephron was not correlated consistently with that of chloride. The results
      indicate that the distal nephron is an important site for the reabsorption of
      fluoride and they provide additional evidence that HF is the permeating moiety.

PMID- 1990409
TI  - Vitamin D absorption, plasma concentration and urinary excretion of 25
      hydroxyvitamin D in nephrotic syndrome.
AB  - Nephrotic syndrome (NS) is commonly associated with vitamin D deficiency. Urinary
      losses of the protein-bound intermediary metabolite of this vitamin is thought to
      contribute to the deficiency state. The role of possible changes, if any, of
      vitamin D absorption has not been investigated previously in NS. We determined
      intestinal absorption of vitamin D3 as well as plasma concentration and urinary
      excretion of 25-hydroxyvitamin D3 in rats with puromycin aminonucleoside-induced
      NS. In vivo recirculating perfusion technique was employed at 100 and 600 nM
      perfusate concentrations. The results were compared with those obtained in
      animals receiving placebo injections provided with either free access to food
      (normal controls) or those pair-fed with their NS counterparts (pair-fed group).
      The NS group showed heavy proteinuria and hypoalbuminemia. In addition, the NS
      group exhibited marked urinary losses and significantly reduced plasma
      concentration of 25-hydroxyvitamin D. The rate of vitamin D3 absorption (given as
      nmol/100 cm/min) at 100 nM perfusate concentration in the NS group (0.161 +/-
      0.029) was not significantly different from those obtained in the pair-fed group
      (0.202 +/- 0.058) and the normal control group (0.143 +/- 0.053). Likewise, no
      significant difference was found in the rats of vitamin D absorption at 600 nM
      concentration among the NS (1.073 +/- 0.383), pair-fed (0.955 +/- 0.229), and
      normal control (0.756 +/- 0.314) groups. Accordingly, intestinal absorption of
      vitamin D appears to be unaffected by the presence of experimental NS and as such
      the associated vitamin D deficiency can be managed by enteral supplementation.

PMID- 1990410
TI  - Calcium uptake by duodenal epithelial cells is increased during lactation.
AB  - It is known that duodenal absorption of calcium is increased during lactation,
      and, more specifically, it has been shown that duodenal active transport of
      calcium is increased. The energy-requiring step for this active transport process
      is thought to occur at the basolateral membrane of the duodenal epithelial cells,
      where calcium is pumped from the cell into the extracellular fluid. The present
      experiments were carried out to determine whether calcium uptake into duodenal
      epithelial cells is also altered during lactation. Uptake of 45Ca into isolated
      duodenal epithelial cells from lactating animals showed markedly enhanced calcium
      uptake when compared with cells from control animals. Uptake was calcium
      concentration dependent for both groups. Since duodenal epithelial cells are
      known to contain increased calbindin9k, a calcium-binding protein, during
      lactation, calcium uptake was also measured in cells that were preincubated in
      medium containing calcium. In these experiments, the total 45Ca uptake was
      reduced, but the difference between lactating and control remained. These
      experiments show that the uptake of calcium into duodenal epithelial cells is
      among the components of the transcellular calcium transport process which is
      enhanced during lactation.

PMID- 1990412
TI  - The severity of diabetes is a major determinant of myocardial damage in the rat.
AB  - The severity of insulin-dependent diabetes mellitus had a marked effect upon the
      development of myocardial sequelae in the rat. Even with the same degree of
      hyperglycemia, glycosuria, polydipsia, and polyuria, moderately diabetic animals
      did not develop the degenerative ultrastructural changes seen in myocardium from
      more severely diabetic rats. These included decreased cardiocyte size, loss and
      disorganization of myofibrils, and loss of sarcoplasmic reticulum and transverse
      tubules. Since hyperglycemia and glycosuria are frequently used as the primary,
      and often sole, criteria for identifying diabetes in experimental animals, this
      study demonstrates the need to more specifically define the severity of the
      disease in studies of the heart.

PMID- 1990411
TI  - Attenuation of mammary duct development by menhaden oil in BALB/c mice.
AB  - The predominant polyunsaturated fatty acids of the n-6 family found in corn oil
      (CO) are crucial for normal mammary duct formation when fed to animals. However,
      as shown here, not all polyunsaturated fatty acids are equally effective in
      stimulating mammary gland development. The n-3 fatty acids in a 10% menhaden oil
      (MO) diet fed to mice effectively reduced both the diameter and the length of the
      growing mammary ducts. Previously, we demonstrated a similar reduction in duct
      growth by feeding a 10% fat diet high in those saturated fats found in
      hydrogenated cotton seed oil. The inhibited rate of duct maturation caused by
      hydrogenated cotton seed oil was reversed when the mice were allowed to mature on
      a diet containing n-6 fatty acids prior to feeding the saturated fat diet. The
      addition of 1% CO to a 9% hydrogenated cotton seed oil diet fed to immature mice
      was also sufficient to restore duct growth. Mice fed menhaden oil diets, on the
      other hand, continued to show impaired ductal growth well into adulthood.
      Examination of the ovaries from MO-fed mice as compared with CO-fed mice revealed
      significantly fewer corpora lutea. When exogenous progesterone was given to MO
      fed mice, ductal growth was partially restored, but not to the extent seen in
      mice fed corn oil diets. Investigation of the fatty acid contents of livers of
      these mice revealed reduced amounts of arachidonate (20:4) in MO-fed mice when
      compared with CO-fed animals. The addition of 1% CO to the 9% MO diets did not
      alter the arachidonate content, indicating a block in the conversion of linoleate
      (18:2) to 20:4 by the n-3 fatty acids. Hence, dietary n-6 fatty acids are
      essential for normal mammary ductal development when fed prior to maturation.
      Although saturated rats are ineffective, n-3 fatty acids can partially substitute
      for the required n-6 fatty acids in both ductal and ovarian development.

PMID- 1990413
TI  - [What is your diagnosis? Algodystrophy of the right hip].

PMID- 1990414
TI  - [AIDS or hepatitis B: what is more dangerous for medical personnel?].

PMID- 1990415
TI  - [The problems of rapid diagnosis of Clostridium difficile as causative agent of
      antibiotic-associated pseudomembranous colitis].
AB  - This paper compares three common methods for the detection of Clostridium
      difficile, i.e. latex agglutination, culture and cytotoxic activity. The
      sensitivity of the latex agglutination test alone is 70%, of the culture 100% and
      of the cytotoxin test 66%. Specificities are 93, 96 and 100%, respectively. The
      latex agglutination has positive and negative predictive values of 58 and 96%;
      the respective values for the culture are 77 and 100%, for the cytotoxin assay
      100 and 96%. Whereas all tests are fairly reliable for the exclusion of diarrhea
      associated to Clostridium difficile (CAD), the positive predictive values of
      latex agglutination and culture are too low. If one requests two positive test
      results for proof of CAD, about two third of all cases are detected by any
      combination of laboratory tests, while the specificity approaches 100%. We
      recommend that two of the three tests are performed; the choice is influenced by
      the possibilities of the laboratory.

PMID- 1990417
TI  - [Should gallstones be crushed?].

PMID- 1990416
TI  - [A case from practice (205). HIV-infection, CDC classification IV C1 and C2
      (candida stomatitis and esophagitis)].

PMID- 1990418
TI  - [The diagnosis of Cushing's syndrome. Results of diagnostic assessment of 20
      patients with Cushing's syndrome of variable etiology (1979-1989)].
AB  - In the light of 20 cases of Cushing's syndrome the currently used diagnostic
      strategies are presented. For initial screening the classical dexamethasone
      suppression test using 1 mg dexamethasone p.o. and 24-hour urinary extraction of
      free cortisol were used, and diagnosis was confirmed using the 2 mg dexamethasone
      suppression test for two days. All three tests had a sensitivity of 100% in these
      20 patients. Etiological evaluation was performed using basal ACTH plasma
      concentration measurement and the more recently available stimulation tests using
      corticotropin-releasing factor (CRF): in cases with suspected pituitary
      hypothalamic etiology, selective catheterisation of the sinus petrous inferior
      with simultaneous blood sampling for measurement of plasma ACTH concentration was
      performed. Detailed etiological diagnosis is important in Cushing's syndrome
      since therapeutic measures differ widely: the etiologies in the 20 patients with
      Cushing's syndrome were: central Cushing's disease (microadenoma in 11, pituitary
      carcinoma in 1), adrenal carcinoma (3), adrenal adenoma (1), adrenal hyperplasia
      (1), ectopic ACTH production (2) and alcohol-induced Cushing's syndrome (1). The
      stepwise procedure in screening and diagnosis of the various etiologies of
      Cushing's syndrome are presented and the results of the 20 patients compared with
      the literature.

PMID- 1990419
TI  - [Toxoplasma infestation: prevalence, risk of congenital infection and development
      in Geneva from 1973 to 1987].
AB  - Assessment of the risk of toxoplasma infection during pregnancy in the female
      population of the Geneva area, and of the risk of congenital toxoplasmosis, has
      shown 9 cases of toxoplasmosis for 1000 pregnancies and 3.5 congenital infections
      for 1000 newborn infants. These results show that the prevalence of toxoplasma
      infection has been decreasing constantly during the 15 years of study, but that
      the risk of infection during pregnancy and of congenital infection has remained
      steady.

PMID- 1990420
TI  - [Risk factors in breast carcinoma].
AB  - A group of 992 breast cancer patients (risk group, R) was compared with a group
      of 482 patients hospitalized for non oncologic reasons and matched for age and
      year of hospitalization (comparison group, C). The findings confirm the following
      factors as risk factors for breast cancer: nulliparity (R 28.8%, C 17.5%, p less
      than 0.001), late first birth (over 34 years of age) (R 11.4%, C 5.1%, p less
      than 0.001), diabetes mellitus (R 7.0%, C 3.8%, p = 0.017), hypertension (R
      25.7%, C 18.1%, p = 0.0016), alcohol (R 9.4%, C 5.9%, p = 0.03), positive family
      history (R 14.8%, V 5.3%, p less than 0.001) and breast surgery for benign
      disease (R 13%, C 7.5%, p = 0.002). Frequently mentioned risk factors such as
      early menarche and late menopause did not emerge as risk factors in our study.
      Cigarette smoking did not show a protective effect but even tended to be more
      frequent in the risk group. Multiparity (more than 2 births) was protective (R
      22.1%, C 32.4%, p less than 0.001). The findings on hormonal replacement therapy
      (R 7.1%, V 17.0%, p less than 0.01) might have been influenced by a selection
      bias (hospitalization of patients in the comparison group because of
      complications of hormonal replacement therapy such as bleeding) and are thus not
      fully conclusive. It can at least be said that hormonal replacement therapy is
      not more frequent in the risk group.

PMID- 1990421
TI  - [Atypical giant cell arteritis].
AB  - The atypical clinical course of giant-cell arteritis in the elderly (who may
      develop a clinical picture of severe consumptive disease) is illustrated by two
      observations with histologically confirmed temporal arteritis. In addition to
      fever and loss of weight, the inflammatory vascular process in a 78-year old
      female was reflected in arrhythmias (atrial fibrillation and atrial flutter),
      probably due to involvement of the coronary arteries, and occlusion of the left
      axillary artery. Similar general symptoms and various neurological deficits
      comprising amaurosis, mononeuritis multiplex, polyneuropathy, myopathy and
      finally subarachnoid hemorrhage characterized the disease in a 72-year-old man.
      The picture was further complicated by intestinal perforation. In both patients
      steroids brought considerable improvement and the disease process came to a
      standstill.

PMID- 1990422
TI  - [Concerning:"Posterior shoulder dislocation" by G. Blatter and P. Suter (Schweiz.
      med. Wschr. 1990; 120: 1400-1405)].

PMID- 1990423
TI  - Cystic fibrosis research.
AB  - In Virginia Morell's Research News article "New light on writing in the Americas"
      (18 Jan., p. 268), the illustrations on page 268 should have been credited to
      George Stuart of the National Geographic Society.

PMID- 1990424
TI  - NIH: the price of neglect.

PMID- 1990425
TI  - U.S. bio-defenses faulted by GAO.

PMID- 1990426
TI  - Is NIH failing an AIDS "challenge"?

PMID- 1990427
TI  - Molecular scissors: RNA enzymes go commercial.

PMID- 1990428
TI  - Population aging policies in East Asia and the United States.
AB  - As a result of successful efforts to reduce fertility and mortality, East Asian
      populations are beginning to age, in some cases rapidly. Policies in response to
      population aging range from attempts in Singapore to reverse it by encouraging
      more births to efforts in Japan to accommodate it by increasing employment
      opportunities for older workers. The population of the United States, which had a
      longer postwar baby boom, is aging more slowly than these two countries and may
      be able to learn from the East Asian experience with aging policies.

PMID- 1990429
TI  - Identification of the 1H-NMR spectra of complex oligosaccharides with artificial
      neural networks.
AB  - Artificial networks can be used to identify hydrogen nuclear magnetic resonance
      (1H-NMR) spectra of complex oligosaccharides. Feed-forward neural networks with
      back-propagation of errors can distinguish between spectra of oligosaccharides
      that differ by only one glycosyl residue in twenty. The artificial neural
      networks use features of the strongly overlapping region of the spectra (hump
      region) as well as features of the resolved regions of the spectra (structural
      reporter groups) to recognize spectra and efficiently recognized 1H-NMR spectra
      even when the spectra were perturbed by minor variations in their chemical
      shifts. Identification of spectra by neural network-based pattern recognition
      techniques required less than 0.1 second. It is anticipated that artificial
      neural networks can be used to identify the structures of any complex
      carbohydrate that has been previously characterized and for which a 1H-NMR
      spectrum is available.

PMID- 1990430
TI  - A new method for carbon isotopic analysis of protein.
AB  - The reaction of ninhydrin with amino acids can be used in carbon isotopic studies
      of protein. The reaction can be applied to extract as carbon dioxide only peptide
      bonded carbon in proteinaceous material, thus avoiding most, if not all,
      contaminants. Test radiocarbon dates on ancient bone indicate that the method
      provides reliable ages, and stable carbon isotopic data suggest that our
      understanding of isotopic dietary reconstruction needs detailed examination. The
      technique should also be useful in biochemical tracing experiments and in global
      carbon budget studies, and the underlying principle may be applicable to other
      isotopes and molecules.

PMID- 1990431
TI  - Transducin activation by rhodopsin without a covalent bond to the 11-cis-retinal
      chromophore.
AB  - Rhodopsin and the visual pigments are a distinct group within the family of G
      protein-linked receptors in that they have a covalently bound ligand, the 11-cis
      retinal chromophore, whereas all of the other receptors bind their agonists
      through noncovalent interactions. The retinal chromophore in rhodopsin is bound
      by means of a protonated Schiff base linkage to the epsilon-amino group of Lys
      296. Two rhodopsin mutants have been constructed, K296G and K296A, in which the
      covalent linkage to the chromophore is removed. Both mutants form a pigment with
      an absorption spectrum close to that of the wild type when reconstituted with the
      Schiff base of an n-alkylamine and 11-cis-retinal. In addition, the pigment
      formed from K296G and the n-propylamine Schiff base of 11-cis-retinal was found
      to activate transducin in a light-dependent manner, with 30 to 40% of the
      specific activity measured for the wild-type protein. It appears that the
      covalent bond is not essential for binding of the chromophore or for catalytic
      activation of transducin.

PMID- 1990432
TI  - Cortical computational maps control auditory perception.
AB  - Mustached bats orient and find insects by emitting ultrasonic pulses and
      analyzing the returning echoes. Neurons in the Doppler-shifted constant-frequency
      (DSCF) and frequency-modulated (FM-FM) areas of the auditory cortex form maps of
      echo frequency (target velocity) and echo delay (target range), respectively.
      Bats were trained to discriminate changes in echo frequency or delay, and then
      these areas were selectively inactivated with muscimol. Inactivation of the DSCF
      area disrupted frequency but not delay discriminations; inactivation of the FM-FM
      area disrupted delay but not frequency discriminations. Thus, focal inactivation
      of specific cortical maps produces specific disruptions in the perception of
      biosonar signals.

PMID- 1990433
TI  - Protein kinase C and regulation of the local competence of Xenopus ectoderm.
AB  - The limited competence of embryonic tissue to respond to an inductive signal has
      an essential, regulatory function in embryonic induction. The molecular basis for
      the competence of Xenopus ectoderm to differentiate into neural tissue was
      investigated. Dorsal mesoderm or 12-O-tetradecanoyl phorbol-13-acetate (TPA)
      caused in vivo activation of protein kinase C (PKC) and neural differentiation
      mainly in dorsal ectoderm and to a lesser extent in ventral ectoderm. These data
      correlate with the observations that PKC preparations from dorsal and ventral
      ectoderm differ, the dorsal PKC preparation being more susceptible to activation
      by TPA and diolein than is the ventral PKC preparation. Monoclonal antibodies
      against the bovine PKC alpha plus beta or gamma isozymes immunostained dorsal and
      ventral ectoderm, respectively, which suggests different localizations of PKC
      isozymes. These results suggest that PKC participates in the establishment of
      embryonic competence.

PMID- 1990434
TI  - Virus hunting and the scientific method.

PMID- 1990435
TI  - Biotech nightmare: does Cetus own PCR?

PMID- 1990436
TI  - New center to study therapies and ethnicity.

PMID- 1990437
TI  - Retroposons--seeds of evolution.

PMID- 1990438
TI  - Light-directed, spatially addressable parallel chemical synthesis.
AB  - Solid-phase chemistry, photolabile protecting groups, and photolithography have
      been combined to achieve light-directed, spatially addressable parallel chemical
      synthesis to yield a highly diverse set of chemical products. Binary masking, one
      of many possible combinatorial synthesis strategies, yields 2n compounds in n
      chemical steps. An array of 1024 peptides was synthesized in ten steps, and its
      interaction with a monoclonal antibody was assayed by epifluorescence microscopy.
      High-density arrays formed by light-directed synthesis are potentially rich
      sources of chemical diversity for discovering new ligands that bind to biological
      receptors and for elucidating principles governing molecular interactions. The
      generality of this approach is illustrated by the light-directed synthesis of a
      dinucleotide. Spatially directed synthesis of complex compounds could also be
      used for microfabrication of devices.

PMID- 1990439
TI  - Determination of membrane protein structure by rotational resonance NMR:
      bacteriorhodopsin.
AB  - Rotationally resonant magnetization exchange, a new nuclear magnetic resonance
      (NMR) technique for measuring internuclear distances between like spins in
      solids, was used to determine the distance between the C-8 and C-18 carbons of
      retinal in two model compounds and in the membrane protein bacteriorhodopsin.
      Magnetization transfer between inequivalent spins with an isotropic shift
      separation, delta, is driven by magic angle spinning at a speed omega r that
      matches the rotational resonance condition delta = n omega r, where n is a small
      integer. The distances measured in this way for both the 6-s-cis- and 6-s-trans
      retinoic acid model compounds agreed well with crystallographically known
      distances. In bacteriorhodopsin the exchange trajectory between C-8 and C-18 was
      in good agreement with the internuclear distance for a 6-s-trans configuration
      [4.2 angstroms (A)] and inconsistent with that for a 6-s-cis configuration (3.1
      A). The results illustrate that rotational resonance can be used for structural
      studies in membrane proteins and in other situations where diffraction and
      solution NMR techniques yield limited information.

PMID- 1990440
TI  - Endothelial expression of a mononuclear leukocyte adhesion molecule during
      atherogenesis.
AB  - An inducible rabbit endothelial adhesion molecule that is selective for
      mononuclear leukocytes has been identified. This adhesion protein was expressed
      on the surface of activated cultured endothelium in two forms, 118 and 98
      kilodaltons, the amino-terminal sequence of each being highly homologous to human
      VCAM-1. In dietary hypercholesterolemic and Watanabe heritable hyperlipidemic
      rabbit models of atherosclerosis, this adhesion molecule was found to be
      expressed in a localized fashion by aortic endothelium that overlies early foam
      cell lesions. This lesion-localized expression suggests a potential endothelium
      dependent mechanism for mononuclear leukocyte recruitment during atherogenesis
      and may provide a molecular marker for early atherosclerosis.

PMID- 1990441
TI  - Human immunodeficiency virus infection of human-PBL-SCID mice.
AB  - Severe combined immunodeficient (SCID) mice reconstituted with human peripheral
      blood leukocytes (hu-PBL-SCID mice) have inducible human immune function and may
      be useful as a small animal model for acquired immunodeficiency syndrome (AIDS)
      research. Hu-PBL-SCID mice infected with human immunodeficiency virus-1 (HIV-1)
      contained virus that was recoverable by culture from the peritoneal cavity,
      spleen, peripheral blood, and lymph nodes for up to 16 weeks after infection;
      viral sequences were also detected by in situ hybridization and by amplification
      with the polymerase chain reaction (PCR). Mice could be infected with multiple
      strains of HIV-1, including LAV-1/Bru, IIIB, MN, SF2, and SF13. HIV-1 infection
      affected the concentration of human immunoglobulin and the number of CD4+ T cells
      in the mice. These results support the use of the hu-PBL-SCID mouse for studies
      of the pathogenesis and treatment of AIDS.

PMID- 1990442
TI  - Senescence of nickel-transformed cells by an X chromosome: possible epigenetic
      control.
AB  - Transfer of a normal Chinese hamster X chromosome (carried in a mouse A9 donor
      cell line) to a nickel-transformed Chinese hamster cell line with an Xq
      chromosome deletion resulted in senescense of these previously immortal cells. At
      early passages of the A9/CX donor cells, the hamster X chromosome was highly
      active, inducing senescence in 100% of the colonies obtained after its transfer
      into the nickel-transformed cells. However, senescence was reduced to 50% when
      Chinese hamster X chromosomes were transferred from later passage A9 cells. Full
      senescing activity of the intact hamster X chromosome was restored by treatment
      of the donor mouse cells with 5-azacytidine, which induced demethylation of DNA.
      These results suggest that a senescence gene or genes, which may be located on
      the Chinese hamster X chromosome, can be regulated by DNA methylation, and that
      escape from senescence and possibly loss of tumor suppressor gene activity can
      occur by epigenetic mechanisms.

PMID- 1990443
TI  - Translational potentiation of messenger RNA with secondary structure in Xenopus.
AB  - Differential translation of messenger RNA (mRNA) with stable secondary structure
      in the 5' untranslated leader may contribute to the dramatic changes in protein
      synthetic patterns that occur during oogenesis and early development. Plasmids
      that contained the bacterial gene chloramphenicol acetyltransferase and which
      encoded mRNA with (hpCAT) or without (CAT) a stable hairpin secondary structure
      in the 5' noncoding region were transcribed in vitro, and the resulting mRNAs
      were injected into Xenopus oocytes, eggs, and early embryos. During early
      oogenesis, hpCAT mRNA was translated at less than 3 percent of the efficiency of
      CAT mRNA. The relative translational potential of hpCAT reached 100 percent in
      the newly fertilized egg and returned to approximately 3 percent after the
      midblastula transition.

PMID- 1990444
TI  - Conserved sequence and structural elements in the HIV-1 principal neutralizing
      determinant: corrections and clarifications.

PMID- 1990445
TI  - A new and novel approach.

PMID- 1990446
TI  - Predictive value of historical and physical characteristics for the diagnosis of
      child abuse.
AB  - Child abuse by burning may be difficult to recognize, especially since the
      injuries are often small. Historical and physical findings that can be elicited
      in the initial examination can be helpful in initiating a more in-depth
      investigation. An injury inconsistent with the history given or a delay in
      seeking medical treatment were the two most frequent reports that elicited
      suspicion. As isolated findings, however, they had a low predictive value. The
      presence of two or more of 13 factors increased the yield in child abuse
      identification to more than 60%.

PMID- 1990447
TI  - A simple height-specific and rate-specific step test for children.
AB  - Recently an anatomic model was reported for adults that standardized the platform
      height for step tests using an individual's stature and a specified hip angle. In
      order to determine if the model could be used to predict the platform height for
      children, platform heights were calculated and hip angles were measured in 146
      boys and 140 girls ages 6 to 18 years who were divided into four age groups (6 to
      8, 9 to 11, 12 to 15, and 16 to 18 years old). There were no statistical
      differences between measured and calculated hip angles in any of the age groups.
      In order to determine the validity for predicting maximal oxygen consumption from
      stepping using a calculated platform height, three step tests were employed using
      one platform height and stepping frequencies of 22, 26, or 30 ascents/min. Each
      of the tests was administered to 93 6- to 18-year-olds. Correlation coefficients
      between the 15-second recovery heart rate after stepping and maximal oxygen
      consumption measured on a treadmill were .80 at 30 ascents/min, .79 at 26
      ascents/min, and .81 at 22 ascents/min. Each of the correlation coefficients was
      significant at the P less than .01 level. It can be concluded that the model is
      valid for standardizing the platform height for children for use with a single
      stage step test for estimating maximal oxygen consumption.

PMID- 1990448
TI  - Childhood firearms fatalities: the Metropolitan Dade County experience.
AB  - I reviewed the cases of childhood firearms fatalities in the files of the Medical
      Examiner Department of Metropolitan Dade County, in Miami, Florida. Comparison of
      cases during the 5-year period from 1966 through 1970 to those during the 5-year
      period from 1984 through 1988, noting basic epidemiologic parameters, showed that
      death due to firearms is increasing among children aged 14 years and younger.

PMID- 1990449
TI  - Cholesterol screening in a black inner-city pediatric population.
AB  - A screening for total blood cholesterol levels was conducted by the University of
      Louisville Department of Family Practice in association with the National Youth
      Sports Program in Louisville, Kentucky. On May 30, 1987, 224 inner-city children
      between 10 and 16 years of age were tested; 109 (49%) were girls and 115 (51%)
      were boys. All participants were black. Of the entire population, the girls had a
      slightly lower mean level of cholesterol than the boys (160 mg/dL vs 165 mg/dL,
      respectively). Because of the large number of participants aged 10 to 14 years
      (211), this subset of children was studied more closely. In this age group, 47
      (22%) of the children were at moderate risk for future cardiovascular disease and
      48 (23%) were at high risk. The serum cholesterol levels were relatively constant
      in all children until age 12, after which a slight reduction occurred. This
      decrease is more evident in boys. Our study also showed a correlation between
      increased blood cholesterol and above normal weight/height indices (ie, Quetelet
      scores), with nearly 70% of all children having elevated cholesterol levels also
      exhibiting above normal Quetelet scores. We observed no correlation between high
      cholesterol levels and high blood pressure in this study population. Dietary
      intervention is recommended as the initial treatment for elevated cholesterol
      levels in children.

PMID- 1990450
TI  - Infrainguinal revascularization for limb salvage in patients with end-stage renal
      disease.
AB  - We studied the efficacy of infrainguinal bypass for limb salvage in patients with
      end-stage renal disease. The patency of 42 femoropopliteal and femorodistal
      bypasses, performed for limb salvage in 37 patients with end-stage renal disease,
      was assessed with Doppler ultrasonography and dye tests. Patency rates and limb
      salvage were determined by life-table analysis. Average age was 45 years (range,
      28 to 61 years); 23 of the 37 were men. Twenty-three patients had diabetes
      mellitus, and 16 were smokers. Bypass procedures were done in 32 instances while
      the patients were maintained with chronic hemodialysis and in five instances with
      peritoneal dialysis; in five instances the patients had had successful renal
      transplantation. Indications for revascularization included pain at rest,
      nonhealing ulcer, or distal gangrene. Femoropopliteal bypass was done in 32
      limbs; 10 were more distal procedures. Reversed saphenous vein was the conduit in
      30 cases; prosthetic material was used in the remainder. Autogenous material was
      used in all distal bypasses. Four patients required graft revision during the
      initial hospitalization, but none thereafter. Two patients died within the
      operative period, nine within 18 months of operation. Nine major operations were
      required. Three-month cumulative graft patency was achieved in 41 cases and
      corresponding limb salvage in 33 cases; 18-month patency was achieved in 34 cases
      and overall limb salvage in 33 cases. Success of limb salvage most closely
      correlated with preoperative ankle-brachial ratio and level of bypass required.

PMID- 1990451
TI  - Assessment of risk for HIV-1 infection for missionaries in sub-Saharan Africa.
AB  - North American mission boards (N = 82) with programs in sub-Saharan Africa were
      surveyed to identify practices affecting risk of human immunodeficiency virus
      type 1 (HIV-1) infection among international staff. Thirty-four percent of
      participating boards thought risk for HIV-1 infection in missionaries in Africa
      was greater than it was for the general US population, and 53% considered it
      greater for overseas medical staff serving in the region than for domestic health
      care workers. Nevertheless, only 24% of boards had formal AIDS education programs
      for overseas health care workers, and 19% for nonmedical personnel going abroad.
      Medical care provision and acquisition were considered high-risk activities; 42%
      of boards with a known policy acknowledged that disposable injection equipment
      was routinely reused, 68% indicated that immunizations were provided abroad, and
      60% admitted that inoculations were administered by indigenous health care
      workers. The most frequently cited specific suggestion for decreasing the risk of
      HIV-1 infection overseas was the implementation of a walking blood bank program.
      We conclude that current practices and logistic constraints make HIV-1
      transmission possible. Risk reduction strategies include more comprehensive
      health education programs, greater adherence to universal precautions, less
      dependence on the indigenous Third World health care system, and implementation
      of innovative programs for health care delivery.

PMID- 1990452
TI  - Voluntary human immunodeficiency virus testing: acceptance levels and
      identification of seropositive individuals.
AB  - Of 4340 clients of a clinic for those with sexually transmitted diseases who were
      eligible for voluntary, confidential, serologic testing for the human
      immunodeficiency virus, 4246 (97.8%) consented to testing; 23 (0.5%) were
      seropositive. Of 94 persons who declined voluntary testing but who were tested in
      a blinded study, nine (9.6%) were seropositive. Seropositive persons who declined
      voluntary testing did not conceal their association with a risk group, while only
      61% of seropositive individuals who accepted voluntary testing admitted to
      inclusion in a risk group before the test. Voluntary testing appears to be
      insufficient, because 28% of the seropositive individuals were not identified as
      being seropositive; also, there was a significant deficiency associated with
      identification of risk at pretest counseling among persons agreeing to voluntary
      testing.

PMID- 1990453
TI  - Klebsiella pneumonia in the modern era: clinicoradiographic correlations.
AB  - A classic clinical and radiographic picture of Klebsiella pneumonia has emerged
      in the literature. Patients are typically male, older than 48 years, and have a
      history of chronic alcoholism. The majority of these pneumonias are community
      acquired. Bulging interlobar fissures and cavitation are radiographic findings
      said to be distinctive for Klebsiella pneumonia. We prospectively studied 15
      cases of bacteremically proven Klebsiella pneumonia and found clinical and
      radiographic features strikingly different from those described in the
      literature. Immunosuppression (from corticosteroids, cytotoxic chemotherapy,
      neutropenia, hematologic malignancy, and transplantation) now rivals alcoholism
      as the primary risk factor. Cases tended to be nosocomial rather than community
      acquired. Neither bulging interlobar fissure nor cavitation was seen in any case.
      The right upper lobe was involved in 11 of our 15 cases. Pneumonia due to
      Klebsiella oxytoca was more likely to be isolated from patients with bilateral
      infiltrates, while Klebsiella pneumoniae was more likely in patients with
      unilateral infiltrates.

PMID- 1990454
TI  - Adenotonsillectomy in children with sickle cell disease.
AB  - The pediatric patient with sickle cell disease risks having a vasoocclusive
      episode during adenotonsillectomy under general anesthesia. With proper patient
      selection and appropriate perioperative management, adenotonsillectomy can be
      accomplished safely in children with sickle cell disease. We review the
      management of 10 children with sickle hemoglobinopathies who had
      adenotonsillectomy. Indications for surgery were recurrent streptococcal
      infections in four and obstructive sleep apnea in six of these children. No
      complications resulted from any of these procedures, and the mean length of
      postoperative hospitalization was 2.4 days. The principal feature of preoperative
      management was the transfusion of red blood cells to suppress the patient's
      endogenous erythropoiesis and to reduce the concentration of sickle cell
      hemoglobin to less than 30%. Though a prospective, multi-institutional clinical
      trial will ultimately be required to settle the issue of the safest preoperative
      management of children with sickle cell disease, balancing the risks of
      transfusion-related complications against anesthesia-related complications, our
      experience supports the operative safety of hypertransfusion therapy in children
      with sickle cell disease.

PMID- 1990455
TI  - Literacy and laryngectomy: how should one treat head and neck cancer in patients
      who cannot read or write?
AB  - The entire population of otolaryngologists and radiation oncologists (N = 192) in
      active practice in the state of North Carolina were surveyed to assess their
      level of awareness of illiteracy among adults in the United States and to
      determine whether these physicians consider illiteracy in the treatment decision
      process for patients with head and neck cancer. Excluding respondents who did not
      treat patients with head and neck cancer and physicians practicing outside of the
      state of North Carolina, the response rate was 115 of 182, or 63%. Only 26% of
      respondents were able to estimate correctly the prevalence of illiteracy in the
      US adult population. Forty-one percent of respondents, however, stated that they
      did consider their patient's ability to read and/or write before making treatment
      recommendations for head and neck cancer. This survey and accompanying literature
      review suggest that physicians perceive illiteracy as a problem that may have a
      significant impact on patients with head and neck cancer, but lack the data
      needed to enable them to quantify the effect of illiteracy on treatment outcome.
      The study reported is the first step in examining ways in which illiteracy might
      negatively affect patient outcomes.

PMID- 1990457
TI  - Endoscopy versus x-ray studies of the gastrointestinal tract: future health care
      implications.
AB  - I did esophagogastroduodenoscopy in 147 patients and colonoscopy in 59 patients
      who had had gastrointestinal x-ray studies. The endoscopic procedure was done
      within 7 days after the x-ray study and/or while the patient was still
      symptomatic. The barium swallow findings were confirmed in only 40%; in the other
      60%, the x-ray findings could not be confirmed. These unconfirmed x-ray findings
      were false-positive in 37.4%, false-negative in 16.3%, and suboptimal or
      nondiagnostic in 6.2%. The barium enema findings were confirmed in 32%. In the
      other 68%, the x-ray findings were false-positive in 42.3%, false-negative in
      22%, and suboptimal in 3.3%. We conclude that in clinical or private practice,
      relying on x-ray studies alone may be associated with a high margin of diagnostic
      errors. When all factors are considered, the initial cost advantage of the x-ray
      studies appears to be lost. In future recommendations on the continuing dilemma
      of x-ray studies versus endoscopy, consideration should be given to factors other
      than the initial lower price of the x-ray studies.

PMID- 1990458
TI  - Attitude and burden in families of depressed elderly patients: strategies for
      care.
AB  - Family members and others who must care for depressed older adults have received
      relatively little clinical and research attention, despite their extensive
      special needs and burden. Attitudes and burden of caregivers affect the initial
      assessment and continuing treatment of depressed elderly patients. Clinicians can
      focus evaluation and therapeutic efforts to include the needs of family and
      patient. Certain strategies for clinical work with caregivers and patients can
      facilitate optimal care.

PMID- 1990456
TI  - Relationship between blood groups and behavior patterns in men who have had
      myocardial infarction.
AB  - Consistent correlations have been found between physical dysfunctional states and
      blood factors. Some of these disorders have possible psychosomatic components
      (eg, duodenal ulcer, myocardial infarction). This study focused on the
      relationship between blood types and various indices of behavior patterns (eg,
      type A behavior scores, anger ratings) in young patients who had had an initial
      myocardial infarction. Patients with blood type O scored significantly higher on
      type A behavior scales and related indices than those having blood type A. Those
      with blood group B responded on several scales between those with types A and O.
      We discuss the utility of blood groupings in future research in the prediction of
      myocardial infarction, methodologic limitations, the relationship of these
      results to temperament studies, Jenkins Activity Survey subtest patterns, anti-H
      reactivity pattern, and hypotheses relating blood factors and behavioral traits
      in patients with psychosomatic disorders.

PMID- 1990459
TI  - Reactional states in Hansen's disease: practical aspects of emergency management.
AB  - Hansen's disease (leprosy), though not a common condition in the United States,
      can be found in some localities among patients who come to the emergency room for
      treatment. Hansen's disease (HD) is a chronic systemic infectious granulomatous
      disease involving principally the skin, mucosa, nerves, and eyes. The causative
      organism, Mycobacterium leprae, is neither highly contagious nor aggressive, but
      rapid alterations in the immunologic response to M leprae in affected tissues can
      result in acute exacerbations termed "reactions." Since most of the symptoms and
      morbidity in HD are a consequence of these reactional states, they must be
      recognized and treated early to prevent permanent sequelae, especially neurologic
      and ophthalmologic. Drug therapy, physical therapy, and sometimes surgery all
      play a role in minimizing the injury caused by reactions.

PMID- 1990460
TI  - Contemporary use of the disease concept: III. A pedantic failure to change
      behavior regarding the problem of anemia.
AB  - The frequency with which house staff noticed their patients to be anemic, the
      frequency with which they tried to find out why the patients were anemic, and the
      diagnostic accuracy of such endeavors were measured. Next, an intervention was
      conducted in which the teams were lectured on the subject of anemia, given
      reading materials on the subject, and given social encouragement to solve the
      problem. At follow-up no improvement was found in any of the outcome variables.

PMID- 1990461
TI  - Anterolateral ankle dislocation without fracture.
AB  - Dislocation of the tibiotalar joint without associated fracture is rare. We have
      presented a case of open anterolateral ankle dislocation with complete
      ligamentous disruption. In contrast to reports that internal fixation is not
      required to maintain reduction of tibiotalar joint dislocation, we found this
      dislocation to be grossly unstable, requiring both a syndesmotic screw and a
      calcaneotalotibial transfixing pin for stabilization.

PMID- 1990462
TI  - Solid and papillary epithelial neoplasm of the pancreas.

PMID- 1990463
TI  - Paratesticular myxoma: an unusual benign intrascrotal neoplasm.
AB  - We have presented a case of paratesticular myxoma and have described the clinical
      history, findings on light microscopy and immunohistochemistry, and possible
      pathogenesis. Although primary paratesticular myxoma is a rare lesion, it should
      be considered in the differential diagnosis of intrascrotal mesenchymal tumors.

PMID- 1990464
TI  - Wernicke-Korsakoff syndrome complicating T-cell lymphoma: unusual or
      unrecognized?
AB  - Malnutrition rather than alcohol abuse is the common element in most cases of
      WKS. Our report may be the first to identify both the clinical and
      neuropathologic features of the syndrome in a patient with T-cell lymphoma. The
      coincidence of these two illnesses underscores a need to consider Wernicke's
      encephalopathy in debilitated individuals with malignancy or other chronic
      illnesses, highlights an atypical presentation of acute Wernicke's
      encephalopathy, and demonstrats the precipitation of that syndrome by glucose
      feeding. Attention to a patient's nutritional status and the liberal use of
      thiamine may prompt early recognition of the syndrome or prevent it entirely.

PMID- 1990465
TI  - Giant cell interstitial pneumonia.
AB  - Giant cell interstitial pneumonia is a distinctive and uncommon form of
      interstitial pneumonia. It is distinguished by the prominence of large, actively
      phagocytic alveolar giant cells of histiocytic origin in the presence of chronic
      interstitial pneumonia. Multinucleated type 2 granular pneumocytes are also
      identified. The multinucleated cells lack viral intranuclear inclusions of the
      type seen in measles pneumonia. Giant cell interstitial pneumonia may be
      idiopathic or it may occur with occupational exposure to hard metals or cobalt.
      We report this case to give recognition to an uncommon interstitial pneumonia.

PMID- 1990466
TI  - Mesenteric volvulus in a patient with anorexia nervosa.

PMID- 1990467
TI  - Recurrent rhabdomyolysis in association with cocaine use.
AB  - As the popularity of cocaine increases in our society, so does the frequency and
      variety of medical complications associated with its use. A growing number of
      cases have implicated cocaine use in the development of rhabdomyolysis and its
      complication, acute renal failure. We have reported the first case of recurrent
      rhabdomyolysis and acute renal failure directly associated with cocaine use.
      Although adulterants might cause muscle damage, we believe cocaine should be
      added to the list of drugs that are capable of producing rhabdomyolysis.

PMID- 1990468
TI  - Necrotizing tracheobronchitis: complication of mechanical ventilation in an
      adult.
AB  - A 51-year-old woman had localized interstitial pneumonia that rapidly progressed
      to involve all lung fields. After 9 days of conventional mechanical ventilation,
      pneumothorax developed in the presence of an obstruction of the right main
      bronchus. Bronchoscopy and endobronchial biopsies revealed NTB involving the
      tracheobronchial tree distal to the tip of the endotracheal tube, with complete
      obstruction of the right main bronchus by hard, eschar-like material. Tracheal
      mucosa proximal to the tip of the endotracheal tube was normal. Subsequent
      bronchoscopy, 20 days later, showed marked resolution of NTB. Though a frequent
      complication of mechanical ventilation in the neonate, NTB as a complication of
      conventional mechanical ventilation has not previously been recognized in an
      adult. Necrotizing tracheobronchitis should be suspected in adults who have had
      mechanical ventilation and who are experiencing ventilatory difficulties, after
      routine problems have been treated or excluded.

PMID- 1990469
TI  - Cavitary Pneumocystis carinii pneumonia in patients receiving aerosol pentamidine
      prophylaxis.
AB  - We have described two patients with AIDS who had cavitary Pneumocystis carinii
      pneumonia while receiving aerosolized pentamidine prophylaxis. This is the first
      report of this complication. Neither patient showed a clinical response to
      subsequent use of pentamidine either intravenously or by aerosol followed by
      intravenous use. Clinicians should be aware of the possibility that cavitary
      pneumonia in patients receiving aerosolized pentamidine may be due to P carinii.

PMID- 1990470
TI  - Successful pregnancy in a patient receiving hemodialysis.
AB  - Pregnancy is an unusual occurrence in women with ESRD. We report a successful
      pregnancy in a patient with ESRD who was receiving hemodialysis; she gave birth
      to a healthy female infant at 34 weeks' gestational age. We discuss possible
      physiologic causes of gonadal dysfunction in patients with ESRD.

PMID- 1990471
TI  - Deep venous thrombosis in intravenous cocaine abuse mimicking septic arthritis of
      the shoulder.
AB  - We describe two patients with deep venous thrombosis of the upper extremity who
      initially were thought to have septic arthritis of the shoulder. These patients
      had a history of recent intravenous cocaine abuse. The diagnosis of deep venous
      thrombosis should be considered when a patient with a swollen shoulder has an
      appropriate history.

PMID- 1990472
TI  - Cerebrospinal fluid losses through ventricular catheters leading to hyponatremia
      in two children.
AB  - I have presented two cases of patients with hyponatremia due to excessive
      cerebrospinal fluid losses from ventricular drains. The possibility of such
      losses exists whether the drain is used to treat hydrocephalus or to monitor
      intracranial pressure. I find normal saline (sodium concentration = 154 mEq/L) to
      be an appropriate fluid to replace ongoing losses of cerebrospinal fluid from a
      ventricular drain and currently start such replacement therapy (mL for mL) when
      the drain is placed.

PMID- 1990473
TI  - High mortality among patients with the leukemoid reaction and alcoholic
      hepatitis.
AB  - We describe a patient with severe alcoholic hepatitis, markedly elevated white
      blood cell count, and high fever. After review of the English literature, we
      discovered reports of other cases similar to our case. The striking feature in
      all of these cases was a high short-term mortality rate, despite predictions of a
      favorable outcome. We therefore believe these patients represent a subgroup of
      patients with alcoholic hepatitis and that the leukemoid reaction is a poor
      prognostic sign in this disease.

PMID- 1990474
TI  - Metoclopramide-induced acute congestive heart failure.

PMID- 1990475
TI  - Colitis due to antituberculous chemotherapy.

PMID- 1990477
TI  - Outcomes management.

PMID- 1990476
TI  - Effects of the calcium antagonist nilvadipine on focal cerebral ischemia in
      spontaneously hypertensive rats.
AB  - We studied the efficacy of preischemic and postischemic systemic treatment with a
      new calcium antagonist nilvadipine in a permanent focal cerebral ischemia model
      of spontaneously hypertensive rats. Rats that underwent microsurgical middle
      cerebral artery occlusion were blindly assigned to a single intraperitoneal
      injection of nilvadipine (0.32 mg/kg) or the same amount of polyethylene glycol
      either 15 minutes before, immediately after, 1 hour after, or 3 hours after
      occlusion of the left middle cerebral artery. Neurologic conditions of rats were
      closely examined, and rats were killed 24 hours later. Removed brains were sliced
      coronally, stained with triphenyltetrazolium chloride, and the size of infarct
      was determined. Although no neurologic improvements were observed in the treated
      rats, the area of infarcts was significantly reduced in the groups treated
      before, immediately after, and 1 hour after occlusion of the middle cerebral
      artery. Treatment started 3 hours after occlusion was ineffective.

PMID- 1990478
TI  - Astroblastoma: electron microscopy and immunohistochemical findings: case report.
AB  - The clinical, histological, immunohistochemical, and electron microscopic
      features of a cerebral astroblastoma are reported. The patient is a young woman
      with a superficial parietal tumor. Macroscopic findings include a well-delineated
      superficial nodule with a hard central core. Histological study disclosed a
      predominantly papillary tumor with hyalinized vessels. Tumor cells were scarcely
      positive with immunohistochemical stain for glial fibrillary acidic protein,
      extensive and diffusely positive with vimentin and neuron-specific enolase, and
      intensely positive with S-100 and epithelial membrane antigen in the papillary
      areas. Ultrastructural study showed abundant intermediate filaments forming
      bundles in tumoral cytoplasms, membrane junctions, and external laminae when
      cells were in contact with collagen fibers. Based on immunohistochemical and
      ultrastructural characteristics, we believe that the filaments seen in tumor
      cells are mainly vimentin filaments. These peculiar immunohistochemical patterns
      in a glioma may aid in the histological diagnosis of this rare tumor type.

PMID- 1990479
TI  - Intramedullary spinal cord germinoma: case report.
AB  - A case of intramedullary spinal cord germinoma within the conus medullaris, with
      lumbago and pain in the lower extremities, is presented. The intramedullary
      spinal cord germinoma was determined by a biopsy specimen. After local
      irradiation of 50 Gy, the tumor markedly decreased in size and clinical symptoms
      disappeared.

PMID- 1990480
TI  - Glossopharyngeal schwannoma: review of five cases and the literature.
AB  - Glossopharyngeal schwannomas are rare tumors in spite of the fact that acoustic
      schwannomas account for 8%-10% of intracranial tumors. There have been 23
      reported cases in the literature. This report of five cases is the largest series
      of these tumors. The presentation, radiological workup, operation, and long-term
      postoperative results will be presented, along with a review of the literature.

PMID- 1990481
TI  - Multiple medullary venous malformations decreasing cerebral blood flow: case
      report.
AB  - A rare case of multiple medullary venous malformations in the right cerebral
      hemisphere is reported. The literature review yielded only one case of multiple
      medullary venous malformations. Computed tomography scan showed multiple
      calcified lesions with linear contrast enhancement representing abnormal dilated
      vessels and mild atrophic change of the right cerebral hemisphere. Single-photon
      emission computed tomography using N-isopropyl-p-(123I) iodoamphetamine
      demonstrated decreased cerebral blood flow in the right cerebral hemisphere.

PMID- 1990482
TI  - Infarct of the conus medullaris simulating a spinal cord tumor: case report.
AB  - A 71-year-old woman had the sudden onset of a neurogenic bladder and a stepwise
      increase in paraparesis that left her unable to stand or walk. Magnetic resonance
      imaging showed what appeared to be a tumor in the conus medullaris. After
      laminectomy, the lesion was localized by ultrasound examination, and a biopsy was
      performed. The deficits remained unchanged postoperatively. Microscopic
      examination of the biopsy specimen showed necrosis and pathologic changes
      consistent with infarction of the conus medullaris. An anomalous arterial supply
      of the conus medullaris is the most likely cause of this unusual problem. The
      patient gradually regained her ability to walk, but the neurogenic bladder
      persists.

PMID- 1990483
TI  - Ganglioneuroma of the spinal cord.
AB  - This report describes a 2-year-old boy who harbored an intramedullary
      ganglioneuroma involving almost the entire length of the spinal cord. The
      terminology, pathology, and neurobiological behavior of this tumor is discussed.

PMID- 1990485
TI  - Embolism of cerebral tissue: a cause of coagulopathy and cerebral infarction?
      Report of a case.
AB  - We report a case of potentially survivable closed head injury, which was
      complicated by disseminated intravascular coagulation and bilateral cerebral
      infarction. Autopsy disclosed pulmonary emboli composed of cerebral tissue. We
      suggest that the entry of brain tissue into the systemic blood circulation caused
      severe disseminated intravascular coagulation, with consequent thrombosis of
      cerebral veins and spreading infarction.

PMID- 1990484
TI  - Unfavorable outcome following early surgical repair of ruptured cerebral
      aneurysms--a critical review of 238 patients.
AB  - Among 238 consecutive patients admitted early with ruptured cerebral aneurysms,
      surgical repair within 48-72 hours was feasible in 200 cases. Unfavorable
      outcomes among the latter 200 patients are analyzed and discussed in this paper.
      Preoperatively, 148 patients were in Hunt and Hess grades I-III, 33 were in grade
      IV, and 19 in grade V. After clipping of the aneurysm, all patients received a
      regimen of topical intracisternal and intravenous/peroral medication with the
      calcium antagonist nimodipine. The overall rate of unfavorable outcomes was 25%,
      ie, outcome with moderate or severe deficit or lethal outcome. The reasons for
      unfavorable outcomes among these 49 patients were the devastating effect of the
      bleed (severe subarachnoid hemorrhage or additional intracerebral hemorrhage) in
      31 patients (15% of the 200 patients), a surgical complication in 11 (5.5%),
      preoperative rebleeding in three (1.5%), delayed ischemia from vasospasm in one
      (0.5%), and various others in three further patients (1.5%). Unfavorable outcome
      occurred in 11% of patients with preoperative grades I-III, in 52% of patients
      with grade IV, and in 16 of 19 patients with grade V. Among the 141 patients with
      subarachnoid hemorrhage but not intracerebral or intraventricular hematoma, 16
      made an unfavorable outcome, ie, 11% versus 56% among patients with intracerebral
      hematoma/intraventricular hematoma on preoperative computed tomography scan. The
      present data seem to speak in favor of early surgery. Since half of the patients
      with intracerebral hematoma and poor outcome had suffered previous warning leaks,
      it appears to be a continuing challenge to diagnose warning leaks before a
      massive hemorrhage occurs.

PMID- 1990486
TI  - Postulates for brain transplantation.

PMID- 1990487
TI  - Paul C. Bucy, M.D.

PMID- 1990488
TI  - Extracerebral course of the perforating branches of the anterior communicating
      artery: microsurgical anatomical study.
AB  - Damage to the perforating branches arising from the anterior communicating
      artery, because of their blood supply to the septal nuclei and anterior
      hypothalamus, explains the memory impairment and the electrolyte disturbances
      that often follow the surgery of aneurysms located in this part of the circle of
      Willis. The microsurgical anatomy of these branches was studied on 60 fixed human
      brains, with special attention to their number, caliber, and vascular territory.
      The direction of the branches was evaluated, measuring the angle formed by them
      with the postcommunicating segment of the anterior cerebral artery. The
      variability of this anatomical region is discussed in light of the literature.

PMID- 1990489
TI  - Memory T cells generated in vitro to class I+, II- hepatocytes.

PMID- 1990490
TI  - The role of antigen presenting cells in secondary mixed lymphocyte hepatocyte
      cultures.

PMID- 1990491
TI  - Comparison of gamma and ultraviolet irradiation on the migration patterns of rat
      dendritic cells and lymphocytes.

PMID- 1990492
TI  - Very late antigen molecules in renal allografts.

PMID- 1990493
TI  - Langerhans cells migrate out of skin grafts and cultured skin: a model in which
      to study the mediators of dendritic leukocyte migration.

PMID- 1990494
TI  - Mechanisms of site-specific immunosuppression.

PMID- 1990495
TI  - Short-term treatment of rats with cyclosporin A causes the appearance of lymph
      node T cells that resemble cortical thymocytes.

PMID- 1990496
TI  - Ultrastructural and immunohistologic study of Kupffer cells in orthotopic
      transplanted rat liver.

PMID- 1990497
TI  - Mechanisms of transplantation tolerance: introduction.

PMID- 1990498
TI  - Mechanism of induction of transplantation tolerance using donor antigen and anti
      CD4 monoclonal antibody.

PMID- 1990499
TI  - I-E molecules and I-E-reactive T cells play a central role in neonatal H-2
      tolerance.

PMID- 1990500
TI  - Mechanisms of prior blood transfusion-cyclosporine-induced tolerance: a potential
      role for immune-cellular chimerism.
AB  - Skin allografts were not enhanced by prior conditioning of blood and CyA (5 or 10
      mg/kg/d). However, when BM-CyA pretreatment was used, SA survival was
      significantly prolonged (CyA, 5 or 10 mg/kg/d). In examining differences between
      the BT-CyA and BM-CyA protocols, equivocal levels of donor microchimerism (1.5%)
      were found in the spleens of BT-CyA conditioned recipients at the time of
      transplantation (day 0). In contrast, highly significant levels of splenic donor
      chimerism (17.2%) developed at day 0 for the BM-CyA pretransplant recipients.
      Skin-allograft prolongation under the BM-CyA protocol implied that the effect may
      be linked to the existence of a donor-specific stem-cell population in the
      recipient animal.

PMID- 1990501
TI  - Donor-specific transfusion and cyclosporine prolong allograft survival when given
      in the peroperative period.

PMID- 1990502
TI  - Characterization of human cardiac-infiltrating cells posttransplantation-
      functional heterogeneity of anti-idiotype cloned T-cell lines with identical
      idiotype specificity.

PMID- 1990503
TI  - The murine immune lymphocyte transfer reaction revisited.

PMID- 1990504
TI  - In vitro function of CD4+ cells of naive and memory phenotype in bone marrow
      transplant recipients.

PMID- 1990505
TI  - In vivo immunologic deficits in mice with murine acquired immunodeficiency
      syndrome and the effect of LP-BM5 infection on rejection of skin from infected
      mice.

PMID- 1990506
TI  - Contribution of CD4+ cells to allorejection across a class I major
      histocompatibility complex barrier in congeneic rats.

PMID- 1990507
TI  - Graft-infiltrating cells produce much more B-cell stimulating factor 2 compared
      with spleen, peripheral blood, and regional lymph node cells.

PMID- 1990508
TI  - Effect of selective depletion of natural killer cells on allograft rejection.

PMID- 1990509
TI  - Nitric oxide production regulates alloactivation in rat splenocyte mixed
      lymphocyte cultures.

PMID- 1990510
TI  - The role of passenger leukocytes in the immunogenicity of intestinal and cardiac
      allografts in the rat.

PMID- 1990512
TI  - SK&F 105685: a novel immunosuppressive compound with efficacy in animal models of
      autoimmunity and transplantation.

PMID- 1990511
TI  - Renal transplantation in miniature swine: preliminary evidence that graft
      infiltrating leukocytes suppress donor-specific cell-mediated lymphocytotoxicity
      in co-culture.

PMID- 1990513
TI  - Accommodation: a working paradigm for progressing toward clinical discordant
      xenografting.

PMID- 1990514
TI  - Immunobiology of the xenograft response: xenograft rejection in immunodeficient
      animals.
AB  - These studies provide insight into the immunobiology of xenograft rejection. They
      suggest that xenograft rejection involves T-cell phenomena, although the ability
      of the nude rat (functionally known to be T-cell deficient) to reject the
      vascularized xenograft normally is striking and clearly indicates a need for
      future studies of this phenomenon. These studies strongly suggest a role for NK
      and K cell-type activity in xenograft rejection, although they also indicate this
      immune function is only an ancillary one and that xenograft rejection will
      eventually occur despite deficiencies in these systems. These studies are most
      provocative in showing a failure of efficiency of skin graft rejection in the
      purest model of B-cell deficiency, the XID model. Since these results are
      obtained with the so-called secondarily vascularized xenograft (skin grafts) it
      is not possible to exclude the role of B-cell and B-cell-associated phenomena in
      vascularized organ grafts without further studies.

PMID- 1990515
TI  - Therapy with 15-deoxyspergualin and total lymphoid irradiation blocks xenograft
      rejection and antibody formation after xenografting.

PMID- 1990516
TI  - Long-term survival of hamster heart and skin xenografts in the rat.

PMID- 1990517
TI  - Recognition of allogeneic cis- or trans-encoded HLA-DQ molecules both by alpha
      beta and gamma delta T-cell receptors.

PMID- 1990519
TI  - TNF-alpha is expressed on the surface of kidney proximal tubular cells.

PMID- 1990518
TI  - Macrophage migration into hepatic xenografts in the hamster-to-rat combination.

PMID- 1990520
TI  - Effects of tumor necrosis factor (TNF) and immunotherapy directed against TNF on
      rat cardiac transplants.

PMID- 1990522
TI  - Increased lymphocyte adhesion to allogeneic endothelial cells by interleukin-4
      (IL-4).

PMID- 1990521
TI  - TNF as a mediator of cardiac transplant rejection, including effects on the
      intragraft protein C/protein S/thrombomodulin pathway.

PMID- 1990523
TI  - Effect of cyclosporine A (CyA) on secreted T proteins from T lymphocytes
      stimulated by PMA/calcium ionophore.

PMID- 1990524
TI  - The effects of recombinant human IL-2 in miniature swine.

PMID- 1990525
TI  - Clinical highlights of the 1990 Congress.

PMID- 1990526
TI  - Profile of cytokine production within the rejecting allograft.

PMID- 1990527
TI  - The effect of total lymphoid irradiation (TLI) on interleukin-2 (IL-2) and its
      receptor in the chacma baboon.

PMID- 1990528
TI  - The assay of soluble IL-2R receptor levels in graft microenvironment can be
      helpful in differential diagnosis of transplant dysfunction.

PMID- 1990529
TI  - Levels of interleukin-2 (IL-2) and its receptor (IL-2R) as early indicators of
      graft rejection in TLI-conditioned, transplanted baboons.

PMID- 1990530
TI  - Therapeutic strategies targeted at CD4+ cells obviate accelerated rejection of
      cardiac allografts in sensitized rats.

PMID- 1990531
TI  - Basic science highlights at the 1990 Congress.

PMID- 1990532
TI  - Pretreatment with cyclosporin A (CyA) and anti-interleukin 2 receptor monoclonal
      antibody (IL-2R MAb) abrogates the anti-idiotype response in rat recipients of
      cardiac allografts.

PMID- 1990533
TI  - Synergistic interactions between anti-interleukin-2 receptor (IL-2R) MAb and CyA
      in sensitized rat recipients of cardiac allografts.

PMID- 1990534
TI  - Functional analysis of donor-reactive T cells infiltrating heterotopic cardiac
      transplants: effect of anti-CD4 MAb in vivo.

PMID- 1990535
TI  - A newly established anti-interleukin-2 receptor beta chain (P75) monoclonal
      antibody inhibits the induction of allo-specific cytotoxic lymphocytes in
      combination with anti-interleukin-2 receptor alpha chain (P55) monoclonal
      antibody.

PMID- 1990536
TI  - Soluble HLA and anti-idiotypic antibodies in transplantation: modulation of anti
      HLA antibodies by soluble HLA antigens from the graft and anti-idiotypic
      antibodies in renal and cardiac allograft recipients.

PMID- 1990537
TI  - Do antilymphocyte antibodies play a role in the rejection of liver transplants in
      serum-transfused rats?

PMID- 1990538
TI  - Partial T-cell depletion with monoclonal antibody improves the enhancing effect
      of donor-specific transfusion plus cyclosporine.

PMID- 1990539
TI  - In vitro effects of an immunotoxin reactive with a shared B and T cell activation
      antigen.

PMID- 1990540
TI  - Inhibition of human B cell responses in vitro by RS-61443, cyclosporine A and
      DAB486 IL-2.

PMID- 1990541
TI  - Reversal of blood-induced sensitization by antibody-coated platelets.

PMID- 1990542
TI  - Purification and characterization of human T-cell cyclophilin expressed in
      Escherichia coli.

PMID- 1990543
TI  - The regulation of T-cell antigen receptor signal transduction function.

PMID- 1990544
TI  - Cyclosporine suppression of intracellular activation signal generation is not
      mediated by prolyl-peptidyl isomerase.

PMID- 1990545
TI  - Heparan sulfate augments the splenocyte response to mitogenic stimuli.

PMID- 1990546
TI  - Protection by fish oil from cyclosporine-mediated toxicity to the endocrine
      pancreas.

PMID- 1990547
TI  - Inhibition of antibody production by the immunosuppressive agent, 15
      deoxyspergualin.

PMID- 1990548
TI  - Erythropoietin: a potential immunomodulator?

PMID- 1990549
TI  - T-cell tolerance.

PMID- 1990550
TI  - The effect of calcium blockade with verapamil on experimental cyclosporine
      nephrotoxicity.

PMID- 1990551
TI  - Cyclosporine A directly constricts intrarenal arterioles.

PMID- 1990552
TI  - Should cyclosporine be continued indefinitely?

PMID- 1990553
TI  - Specific elimination of preformed antibody activity against xenogeneic antigens
      by use of an extracorporeal immunoadsorptive circuit.

PMID- 1990554
TI  - Molecular HLA matching.

PMID- 1990555
TI  - Influence of pretransplant sensitization on the survival of corneal allografts.

PMID- 1990556
TI  - Long-term impact of HLA matching on kidney graft survival in cyclosporine-treated
      recipients.

PMID- 1990557
TI  - Matching, race, donor age, and cold ischemia effects at a single renal transplant
      center.

PMID- 1990558
TI  - Stronger immune responsiveness of blacks vs whites may account for renal
      allograft survival differences.

PMID- 1990559
TI  - HLA-DR oligotyping of 100 kidney transplant patients with difficult serological
      typing: correlation between serology and DNA typing.

PMID- 1990560
TI  - Beneficial effects of some donor-recipient HLA-DR mismatches on cadaveric graft
      survival: proposal for a new selection policy of recipients.

PMID- 1990561
TI  - Multiscreen analysis of high PRA sera for antibodies towards public and private
      class I antigens: implications for computer-predicted acceptable donors for
      kidney transplant candidates.

PMID- 1990562
TI  - Amino acid residues on HLA molecules critical for alloantibody binding.

PMID- 1990563
TI  - Human monoclonal autoantibodies produced by B lymphocytes from sensitised
      dialysis patients: functional activity and tissue distribution of the
      autoantigen(s).

PMID- 1990564
TI  - Anti-HLA antibody removal in hyperimmunized ESRF patients to allow
      transplantation. The Collaborative Study Group on Anti-HLA Antibody Removal.

PMID- 1990565
TI  - Improved renal allograft survival for AHG and DTE/AHG crossmatch-negative
      recipients.

PMID- 1990566
TI  - Impaired kidney graft survival in flow cytometric crossmatched positive donor
      specific transfusion recipients.

PMID- 1990567
TI  - High cellular anti-HLA immune responsiveness accompanies the highly sensitized
      (high PRA) state in dialysis patients.

PMID- 1990568
TI  - Recombinant human erythropoietin decreases anti-HLA sensitization and may improve
      renal allograft outcome: involvement of anti-idiotypic antibody.

PMID- 1990570
TI  - The case against the indefinite use of cyclosporine.

PMID- 1990569
TI  - Recombinant erythropoietin: does it really effect sensitization?

PMID- 1990571
TI  - Close association of renal allograft failure and antibody directed against
      epithelial cells.

PMID- 1990572
TI  - Preformed antibodies in predicting clinical renal graft outcome.

PMID- 1990573
TI  - Does a positive historical crossmatch affect long-term renal transplant graft
      survival?

PMID- 1990574
TI  - Renal transplantation with positive allocrossmatch (B/T; historical/current) but
      current T negative.

PMID- 1990575
TI  - Identification of a CD4 polymorphism in swine.

PMID- 1990576
TI  - The H-2D genes influence expression of HLA-B27 in transgenic mice.

PMID- 1990577
TI  - Different biology and pathology of minor alloantigen-specific cytotoxic and
      proliferative T cells.

PMID- 1990578
TI  - Living-related liver donation: CON.

PMID- 1990579
TI  - Significance of B-cell crossmatch on outcome in renal transplantation.

PMID- 1990580
TI  - Allorecognition of HLA-B5 cross reactive group antigens by human CTL clones.

PMID- 1990582
TI  - Analysis of alloreactive responses to the HLA-DR1 alleles.

PMID- 1990581
TI  - DRw11/w13: a structurally and functionally related family of alleles.

PMID- 1990583
TI  - Diversity in the fine specificity of anti-HLA-DR monoclonal antibodies elicited
      with syngeneic antiidiotypic monoclonal antibodies.

PMID- 1990584
TI  - HLA-D region and Hsp70 genes in rheumatoid arthritis.

PMID- 1990585
TI  - Southern and oligonucleotide analyses of HLA-DQw1-associated DR1, DRw6, and DRw10
      specificities in Asian Indians.

PMID- 1990586
TI  - HLA matching should be utilized for improving kidney transplant success rates.

PMID- 1990587
TI  - Two new class I loci in the rat major histocompatibility complex: RT1.L and
      RT1.M.

PMID- 1990588
TI  - Crossmatch with donor skin: characterization of alloantibodies and correlation
      with early kidney rejection.

PMID- 1990589
TI  - Cyclosporine impairs cardiac function in the rat.

PMID- 1990590
TI  - Effect of cyclosporine A treatment on induction of donor specific
      unresponsiveness in mongrel dogs following a short course of ALS and donor bone
      marrow infusion on canine renal allograft function.

PMID- 1990591
TI  - One-year survival of heterotopic heart primate xenografts treated with total
      lymphoid irradiation and cyclosporine.

PMID- 1990592
TI  - Cyclosporine induces reduction of antigen-specific T cytotoxic clones in rats
      transplanted with heart allografts.

PMID- 1990593
TI  - Microvascular changes induced by cyclosporine.

PMID- 1990594
TI  - Effect of steroids on cellular proliferation in rat cardiac allografts.

PMID- 1990595
TI  - Effect of antilymphocyte serum, donor antigen, and graft irradiation on rat
      pancreas allograft survival.

PMID- 1990596
TI  - K-MAP prevents cyclosporine toxicity on islet B cells in rat pancreatic
      transplantation.

PMID- 1990597
TI  - Comparison of the immunosuppressive effects of mycophenolic acid and the
      morpholinoethyl ester of mycophenolic acid (RS-61443) in recipients of heart
      allografts.

PMID- 1990598
TI  - Prolongation of dog renal allograft survival by RS-61443, a new, potent
      immunosuppressive agent.

PMID- 1990599
TI  - The 1990 Peter Medawar Award.

PMID- 1990600
TI  - OKT4A monoclonal antibody immunosuppression of cynomolgus renal allograft
      recipients.

PMID- 1990601
TI  - Prolongation of kidney and skin allograft survival in the rat by monoclonal
      antibody therapy directed to the RT6.1 T-cell alloantigen.

PMID- 1990602
TI  - Prolongation by rapamycin of heart, kidney, pancreas, and small bowel allograft
      survival in rats.

PMID- 1990603
TI  - Intrathoracic transplantation.

PMID- 1990604
TI  - A report from the UNOS Scientific Renal Transplant Registry.
AB  - The UNOS Kidney Transplant Registry is now fully operational. Aside from
      scientific reports from UCLA, analysis of the same data base from investigators
      who initiate projects through UNOS central in Richmond, as well as from HICFA and
      USRDS, can be anticipated. Plans are underway to simplify the reporting process.
      With the large number of accumulated cases, it should be possible to analyze many
      factors in the future. Presently, histocompatibility differences in living
      related vs cadaver donors and degrees of HLA mismatching among recipients of
      cadaveric kidneys are major factors. Immunization by transplant rejection is the
      second most important factor.

PMID- 1990605
TI  - 15-Deoxyspergualin is a more potent and effective immunosuppressant than
      cyclosporine but does not effectively suppress lymphoproliferation in vivo.

PMID- 1990606
TI  - Remarkable recovery from rejection by treatment with deoxyspergualin and
      methylprednisolone on canine kidney allografts.

PMID- 1990607
TI  - Anti-tumor necrosis factor alpha serum prolongs heart allograft survival in rats.

PMID- 1990608
TI  - Registry report on clinical pancreas transplantation.

PMID- 1990609
TI  - Effect of anti-CD4 monoclonal antibody dosage when combined with donor antigen
      for the induction of transplantation tolerance.

PMID- 1990610
TI  - Induction of transplantation tolerance after allogeneic thymus transplantation:
      mechanisms involved.

PMID- 1990611
TI  - Induction of specific tolerance in pancreatic transplantation: an experimental
      model in rats.

PMID- 1990612
TI  - The effect of xenoantibody and formed cellular blood elements on ex vivo
      xenograft hyperacute rejection.

PMID- 1990613
TI  - The involvement of platelet-activating factor in hyperacute xenogeneic rejection
      and its modulation by the PAF-antagonist WEB 2086BS.

PMID- 1990614
TI  - The effect of combined treatment with total lymphoid irradiation, cyclosporin A,
      and anti-CD4 monoclonal antibodies in a hamster-to-rat heart transplantation
      model.

PMID- 1990615
TI  - Liver Transplant Registry Report.

PMID- 1990616
TI  - Both concordant and discordant heart xenografts are rejected by athymic (nude)
      rats with the same tempo as in T cell competent animals.

PMID- 1990617
TI  - Fetal pig pancreas xenografts in non-obese diabetic mice treated with continuous
      anti-CD4 monoclonal antibody.

PMID- 1990619
TI  - Prolonged survival of a discordant cardiac xenograft in a rhesus monkey.

PMID- 1990618
TI  - The effect of 15-deoxyspergualin on hamster-to-rat cardiac xenograft survival.

PMID- 1990620
TI  - IL-2 activated killer cell activity is associated with the early phase of
      allograft rejection.

PMID- 1990621
TI  - Prolongation of hepatic allograft survival in rat recipients treated with anti
      lymphotoxin antibody.

PMID- 1990622
TI  - Replacement of dendritic cells in the airways of allografted rat lungs.

PMID- 1990623
TI  - Progress in bone marrow transplantation for leukemia: a preliminary report from
      the Advisory Committee of the International Bone Marrow Transplant Registry.

PMID- 1990624
TI  - Rat aortic allografts: an experimental model for chronic transplant
      arteriosclerosis.

PMID- 1990625
TI  - Chronic vascular rejection in an inbred rat cardiac model.

PMID- 1990626
TI  - Blood transfusion-induced sensitization in parous inbred rats: influence of
      paternal strain phenotype on alloantibody production.

PMID- 1990628
TI  - Immunologic aspects and complications of composite tissue allografting for upper
      extremity reconstruction: a study in the rhesus monkey.

PMID- 1990627
TI  - In vivo and in vitro study of hyperacute rejection mechanism of renal discordant
      xenograft.

PMID- 1990629
TI  - Advances in and future of tissue typing.

PMID- 1990630
TI  - Interleukin 6 levels in bile following liver transplantation.

PMID- 1990631
TI  - Differential irradiation effects on rat interstitial dendritic cells.

PMID- 1990632
TI  - Arachidonate 5-lipoxygenase inhibition and acute renal allograft rejection.

PMID- 1990633
TI  - Carolina rinse solution protects adenosine triphosphate-depleted hepatocytes
      against lethal cell injury.

PMID- 1990635
TI  - University of Wisconsin solution for kidney preservation: the impermeant
      components.

PMID- 1990634
TI  - Carolina rinse solution increases survival time dramatically after orthotopic
      liver transplantation in the rat.

PMID- 1990636
TI  - A new lung preservation method of topical cooling by ambient cold air: an
      experimental study.

PMID- 1990637
TI  - Amelioration of 3.5-hour warm ischemia time for pig livers by cyclosporine
      pretherapy, compared with azathioprine.

PMID- 1990638
TI  - Improved rat liver preservation using chlorpromazine in a new sodium lactobionate
      sucrose solution.

PMID- 1990639
TI  - 24-hour storage for asphyxiated canine hearts with use of Belzer University of
      Wisconsin solution.

PMID- 1990640
TI  - Use of crystalloids prior to storage in University of Wisconsin solution is
      deleterious in liver preservation.

PMID- 1990641
TI  - Future trends in transplantation in the 1990s: prospects for the induction of
      clinical tolerance.

PMID- 1990642
TI  - Extended lung preservation by bronchial artery perfusion with University of
      Wisconsin solution.

PMID- 1990643
TI  - Histology of host and graft lymphoid tissue in a chronic orthotopic bowel
      allograft model in the rat.

PMID- 1990644
TI  - Monitoring in small bowel transplantation using cytochemistry and
      immunochemistry: a comparison of different techniques.

PMID- 1990645
TI  - Simultaneous occurrence of graft-versus-host and host-versus-graft reactions
      after allogenic MHC class II disparate small bowel transplantation in
      immunocompetent rats.

PMID- 1990646
TI  - Donor pretreatment with monoclonal antibody for prevention of graft-versus-host
      disease following small bowel transplantation: effect of depletion of T-cell
      subsets.

PMID- 1990647
TI  - Inhibitory effect of cyclosporine on specific secretory IgA production against
      cholera toxin in small bowel transplantation.

PMID- 1990648
TI  - Ex vivo depletion of graft T lymphocytes in small intestinal transplantation.

PMID- 1990649
TI  - Successful canine small intestinal allotransplantation: ex vivo irradiation and
      cyclosporine pretreatment.

PMID- 1990650
TI  - Effects of two-step small bowel transplantation on intestinal morphology and
      function.

PMID- 1990651
TI  - Recurrent diabetes in pancreas transplants in the BB rat: evidence for a defect
      extrinsic to the beta cell.

PMID- 1990652
TI  - Improved survival of kidneys preserved for seven days with a phospholipase
      inhibitor.

PMID- 1990653
TI  - A new slow delivery type of superoxide dismutase prevents warm ischemia damage in
      swine orthotopic liver transplantation.

PMID- 1990654
TI  - Extending the limits of donor heart preservation: a trial with University of
      Wisconsin solution.

PMID- 1990655
TI  - Effect of splenectomy and mono- or combination therapy with rapamycin, the
      morpholinoethyl ester of mycophenolic acid and deoxyspergualin on cardiac
      xenograft survival.

PMID- 1990656
TI  - First Medawar prize lecture. The recirculating small lymphocyte.

PMID- 1990657
TI  - ABO-incompatible transplantation in pigtail macaque monkeys.

PMID- 1990658
TI  - Allogeneic orthotopic liver transplantation in mice: a preliminary study of
      rejection across well-defined MHC barriers.

PMID- 1990659
TI  - Correlation between microvascular damage and hepatic clearance in swine liver
      transplantation.

PMID- 1990660
TI  - Nuclear magnetic resonance and biochemical studies to determine the synergistic
      detrimental effects of renal ischemia on cyclosporine nephrotoxicity in the rat.

PMID- 1990661
TI  - Sex-associated differences in organ transplantation: different effects of steroid
      hormones, testosterone, estradiol, progesterone, and prednisolone on the survival
      time of allogeneic skin graft in rats treated with cyclosporin A.
AB  - Adult male recipients could accept allogeneic skin graft with CyA treatment alone
      for considerably long periods, whereas young male and female, and adult females
      were not susceptible to the immunosuppression. When testosterone or prednisolone
      was administered with CyA as a combination therapy to young male and adult female
      recipients, the survival time of the graft was significantly prolonged. On the
      contrary, estradiol totally inhibited the immunosuppressive activity of CyA in
      any recipients. These present data strongly suggested that immunoreactivity
      against transplantation antigens can be influenced by sex steroid hormones, and
      that the usage of steroid combination therapy may overcome the lack of
      immunosuppression by CyA induced by the female sex steroid estradiol.

PMID- 1990662
TI  - Heterotopic liver transplantation corrects the inborn error of hepatic metabolism
      in a dog model.

PMID- 1990663
TI  - Cyclosporine-induced alterations in renal, intrarenal, and pancreatic blood flow.

PMID- 1990664
TI  - Prevention of ischemic sinusoidal lining cell injury during liver transplantation
      in pigs using an artificial heart and lung.

PMID- 1990665
TI  - Donor-specific unresponsiveness to cardiac allografts in the mouse: an
      examination of mechanisms.

PMID- 1990666
TI  - Do small B cells induce tolerance?

PMID- 1990667
TI  - Cellular transplants.

PMID- 1990668
TI  - Requirements for tolerance induction to pig proislet xenografts in mice.

PMID- 1990669
TI  - Tolerance induction in adult mice: cyclosporine inhibits RS-61443-induced
      tolerance.

PMID- 1990670
TI  - Successful transfer of donor-specific transplantation tolerance by adoptive
      transfer of fully allogeneic chimeric bone marrow.

PMID- 1990671
TI  - Enhancement of rabbit cardiac allografts by third-party hepatocytes.

PMID- 1990672
TI  - Vascularized bone marrow transplantation (VBMT): induction of stable mixed T-cell
      chimerism and transplantation tolerance in unmodified recipients.
AB  - In this preliminary report, our model of VBMT across a semiallogeneic barrier
      consistently brings about antigen-specific host tolerance with absence of GVHD in
      the majority of recipients. No immunologic or radiologic intervention was
      utilized. These results emphasized a potentially important mechanism for low
      level stable mixed lymphoid chimerism (SMLC) in tolerance induction, independent
      of immune suppressive effects due to irradiation or immunopharmacologic
      intervention.

PMID- 1990673
TI  - Temporary anti-CD-25 treatment results in tolerance development in syngeneically
      grafted autoimmune diabetic recipients.

PMID- 1990674
TI  - Islet destruction by the NOD mouse may be mediated by both MHC-restricted and
      nonrestricted mechanisms.

PMID- 1990675
TI  - Possible mechanisms underlying marked islet allograft survival following multiple
      donor allotransplantation.

PMID- 1990676
TI  - Transforming growth factor beta prevents islet allograft rejection.

PMID- 1990677
TI  - The diabetic "human reconstituted" severe combined immunodeficient (SCID-hu)
      mouse: a model for isogeneic, allogeneic, and xenogeneic human islet
      transplantation.

PMID- 1990678
TI  - Reinnervation of transplanted mouse pancreatic islets.

PMID- 1990679
TI  - Fetal liver and pancreas transplanted as a composite improves islet graft
      function.

PMID- 1990680
TI  - The biohybrid artificial pancreas for treatment of diabetes in totally
      pancreatectomized dogs.

PMID- 1990681
TI  - An immunologic basis for the fibrotic reaction to implanted microcapsules.

PMID- 1990682
TI  - Extended survival of purified canine islet allografts with heterologous
      antilymphocyte globulin.

PMID- 1990683
TI  - Prolonged functional survival of rat-to-NOD mouse islet xenografts by ultraviolet
      B (UV-B) irradiation plus microencapsulation of donor islets.

PMID- 1990684
TI  - Cyclosporine is detrimental to islet procurement from adult pancreatic tissue.

PMID- 1990685
TI  - Large scale isolation, function, and transplantation of islets of Langerhans from
      the adult pig pancreas.

PMID- 1990687
TI  - Transplantation of purified single-donor cryopreserved canine islet allografts
      with cyclosporine.

PMID- 1990686
TI  - Islet purification using Euro-Ficoll gradients.

PMID- 1990688
TI  - Mass isolation of highly purified islets from the canine pancreas.

PMID- 1990689
TI  - Reduced immunosuppression for in vitro cultured, pure canine islets transplanted
      from single donors.

PMID- 1990690
TI  - Human islet isolation and purification from pediatric-age donors.

PMID- 1990691
TI  - Metabolic control after autotransplantation of highly purified canine pancreatic
      islets isolated in UW solution.

PMID- 1990692
TI  - Studies of the isolation and transplantation of purified islets in adult humans.

PMID- 1990693
TI  - Transplanted allogeneic fetal dopamine neurons survive and improve motor function
      in idiopathic Parkinson's disease.

PMID- 1990694
TI  - Intraportal islet allografts: the use of a stimulation index to represent
      functional results.

PMID- 1990695
TI  - Expression of major histocompatibility complex antigens on human myoblasts.

PMID- 1990696
TI  - Induction of cell-mediated IL-2-activated antitumor responses in conjunction with
      autologous and allogeneic bone marrow transplantation.

PMID- 1990697
TI  - Sequential analysis by polymerase chain reaction of mononuclear leukocyte
      activation-associated transcription in pancreatic islet cell allograft rejection.

PMID- 1990698
TI  - Long-term acceptance of rat liver allografts induced by intraportal
      administration of donor spleen cells.

PMID- 1990699
TI  - Natural antibody targets on discordant endothelium: molecular characterization
      and consequences of antibody binding.

PMID- 1990700
TI  - Lack of class II antigen expression on hepatocytes profoundly affects CTL
      development in vitro and in vivo.

PMID- 1990701
TI  - The alloimmune response against pancreatic islets is generated by both direct and
      indirect pathways.

PMID- 1990703
TI  - Cluster-function relationship of anti-P55 IL-2 receptor monoclonal antibodies in
      mice.

PMID- 1990702
TI  - Analysis of cellular events within stable and rejecting allografts in cynomolgus
      monkeys.

PMID- 1990704
TI  - Immunologic basis of small intestinal allograft rejection.

PMID- 1990705
TI  - Preservation of postischemic capillary perfusion by selective inhibition of
      leukotriene biosynthesis.

PMID- 1990706
TI  - Immunosuppressive effect of soluble class I antigen and its complexes with
      monoclonal antibody on advanced heart graft rejection in rats.

PMID- 1990707
TI  - Immunological unresponsiveness by deoxyspergualin therapy in mice undergoing
      lethal graft-vs-host disease, and successful adoptive transfer of
      unresponsiveness.

PMID- 1990708
TI  - Inhibition of skin graft rejection in mice by rapamycin: a novel
      immunosuppressive macrolide.

PMID- 1990709
TI  - Effect of cholera toxin on pancreatic islet transplantation in mice.

PMID- 1990710
TI  - Islet xenotransplantation in a pre-clinical large animal model.

PMID- 1990711
TI  - Hyperacute rejection of xenografts in the complete absence of antibody.

PMID- 1990712
TI  - Humoral tolerance in mixed xenogeneic chimeras prepared by a nonmyeloablative
      conditioning regimen.

PMID- 1990713
TI  - Elimination of preformed antibody activity to xenoantigens utilizing dithiol
      reducing agents.

PMID- 1990714
TI  - Transplantation of vascularized bone marrow.

PMID- 1990715
TI  - Effects of fetal liver transplantation in rats with congenital metabolic disease.

PMID- 1990716
TI  - The in vitro immunogenicity of antigen-presenting cell-free endocrine cells: the
      role of antigen presenting cells.

PMID- 1990717
TI  - Hepatocyte transplantation into the lung for treatment of acute hepatic failure
      in the rat.
AB  - The lung was investigated as a matrix for transplanted hepatocytes in the rat
      model. Surgically induced fulminant hepatic failure was successfully treated by
      injection of 5 to 7 x 10(7) isolated hepatocytes into the pulmonary parenchyma in
      86% of the animals. No animal, however, survived injection of hepatocytes into
      the jugular vein. It was found that liver failure is a prerequisite for the
      intrapulmonary survival of hepatocytes. After regeneration of the native liver,
      the majority of hepatocytes are cleared away within 6 months.

PMID- 1990718
TI  - Sustained reduction of serum cholesterol levels following allo-transplantation of
      parenchymal hepatocytes in Watanabe rabbits.

PMID- 1990719
TI  - Improved arterial allograft preservation with the University of Wisconsin
      solution.

PMID- 1990720
TI  - First Medawar prize lecture. The immunological function of the thymus and of the
      thymus-derived lymphocytes.

PMID- 1990721
TI  - The role of antigen-presenting cells in rat corneal graft rejection.

PMID- 1990722
TI  - TiPS receptor nomenclature supplement 1991.

PMID- 1990724
TI  - Ultrasonic phased array controller for hyperthermia applications.
AB  - Multiple and mechanically scanned ultrasound transducer systems have demonstrated
      the efficacy of using ultrasound to produce deep localized hyperthermia. The use
      of ultrasonic phased arrays has been proposed as an alternative to these systems.
      A phased array offers a more flexible approach to heating tumours in that the
      size, shape, and position of its focal region can be altered during the course of
      treatment in order to achieve the desired temperature distribution. This added
      flexibility comes at the cost of increased complexity of the hardware necessary
      to drive the transducer because each element requires its own amplifer with both
      phase and amplitude control. In order for phased arrays with large numbers of
      elements to be feasible for hyperthermia applications, the complexity of this
      circuitry must be minimized. This paper describes a circuit design which
      simplifies the electronics required to control a phased array transducer system
      for hyperthermia applications. The design is capable of controlling virtually any
      type of phased array transducer operating at frequencies less than 2 MHz. The
      system performance was verified through beam profile measurements using a 48
      element tapered phased array transducer.

PMID- 1990723
TI  - Lack of increase in cell transformation frequency of C3H cells after exposure to
      pulsed ultrasound.
AB  - Liebeskind et al. reported that ultrasound from a diagnostic ultrasound unit
      caused an increase in cell transformation of in vitro C3H cells. The objective of
      this study was to attempt verification of this result, using the same cell line
      and a similar ultrasound exposure regimen. Four experiments were undertaken, each
      involving an ultrasound, X-ray (positive control) and sham exposure regimen.
      There was no increase in cell transformation frequency with the ultrasound
      exposure, but a small and statistically significant increase with the X-ray
      regimen.

PMID- 1990725
TI  - A comparative study of fracture strength, ultrasonic properties and chemical
      constituents of kidney stones.
AB  - Ultrasonic properties of kidney stones were studied with a double-probe-through
      transmission technique, the micro hardness was studied using the Viker
      indentation method and the chemical composition studied using an X-ray technique.
      The microhardness is found to vary with chemical composition as well as
      ultrasonic propagation velocity. The comparative results obtained are discussed
      in detail.

PMID- 1990726
TI  - Public-health groups discourage mandatory restrictions on HIV- infected workers.

PMID- 1990727
TI  - "You're not going to believe this, but...".

PMID- 1990728
TI  - Osgood-Schlatter disease.

PMID- 1990729
TI  - Beetle larvae ingestion.

PMID- 1990731
TI  - The National Tuberculosis Training Initiative.

PMID- 1990730
TI  - Dealing with the resurgence of tuberculosis.

PMID- 1990732
TI  - Return of tuberculosis: screening and preventive therapy.
AB  - Approximately 25 percent of individuals exposed to Mycobacterium tuberculosis
      become infected. Of those, about 10 percent will develop clinically active
      tuberculosis at some time in their lives. The tuberculin skin test should be used
      to screen all patients, especially those at greatest risk of contracting the
      disease, such as the young and the old, and those with weakened immune systems
      from poor nutrition, alcohol and drug abuse, chronic illness and human
      immunodeficiency virus infection. Depending on the characteristics of the local
      population and individual medical risk factors, a reaction (induration) between 5
      and 15 mm (or more) generally represents infection. Isoniazid therapy in persons
      with positive skin tests will decrease the risk of disease by 60 to 80 percent.
      Family physicians will play a critical role in efforts to eliminate tuberculosis
      from the United States by the year 2010.

PMID- 1990733
TI  - Tuberous sclerosis.
AB  - Tuberous sclerosis is an inherited disorder characterized by a triad of signs-
      mental retardation, seizures and adenoma sebaceum. The hamartomas that commonly
      affect multiple organ systems can be seen on plain film radiography. Computed
      tomography and ultrasonography are useful for assessing whether lesions are
      present in the abdomen, kidneys and brain. The hamartomas tend to bleed, causing
      symptoms and prompting the need for evaluation.

PMID- 1990734
TI  - Preventing group B streptococcal infection in newborns.
AB  - Group B streptococci, commonly found in the maternal gastrointestinal and
      genitourinary tracts, can be transmitted to the neonate at the time of rupture of
      membranes and during delivery. Current management strategies include early
      detection of group B streptococcal carriers and the administration of intrapartum
      prophylactic antibiotics to prevent maternal fetal transmission. Several tests
      are now available to rapidly identify group B streptococcal carriers. Physicians
      should be able to recognize patients at high risk for colonization and the
      situations in which prophylactic antibiotics should be employed. Proper use of
      antibiotics during labor can eliminate group B streptococcal sepsis in neonates.
      Early group B streptococcal meningitis carries a mortality rate of almost 50
      percent, despite medical support from neonatal intensive care units.

PMID- 1990735
TI  - The painful shoulder: Part II. Intrinsic disorders and impingement syndrome.
AB  - Intrinsic disorders that can cause shoulder pain include arthritis, gout,
      pseudogout and osteonecrosis. In its mildest form, impingement syndrome may cause
      only minimal discomfort. At its worst, impingement syndrome may lead to rotator
      cuff tear. Bicipital tendinitis and rupture of the biceps tendon may also be
      associated with impingement. Early rehabilitative intervention is important.
      Physical therapy is directed toward restoring range of motion and muscle
      strength.

PMID- 1990736
TI  - The cervical cap.
AB  - The cervical cap is a barrier contraceptive method with an efficacy similar to
      that of the diaphragm. It has several advantages over other barrier
      contraceptives. In particular, it can be left in place for up to 48 hours, and
      repeated applications of spermicide are not necessary, even if sexual intercourse
      occurs more than once. In addition, the side effects seen with other barrier
      methods do not occur with the cervical cap. In some women, Papanicolaou tests may
      become abnormal, especially during the first three months of cap use. Therefore,
      careful monitoring of cervical cap users is essential.

PMID- 1990737
TI  - Canes, crutches and walkers.
AB  - Canes, crutches and walkers are safe and effective but generally underutilized
      therapeutic tools. These aids are most helpful to patients who have an unstable
      gait, whose muscles are weak or who require a reduction in the load on weight
      bearing structures. An understanding of the biomechanics of ambulation aids
      provides insights into how and when these devices should be prescribed. The
      patient must have sufficient strength, balance and coordination to master the aid
      and should be trained to use it correctly.

PMID- 1990738
TI  - Mammography and early breast cancer detection.
AB  - Screening mammography has been shown to reduce breast cancer mortality. Both film
      screen mammography and xeromammography are highly sensitive and specific.
      Mammography accreditation programs assure physicians and patients that a facility
      provides mammography of the highest quality, using the lowest possible radiation
      dose. Mammographic signs of early cancer include a small mass, calcifications,
      architectural distortion and a neodensity. Dense tissue may result in a false
      negative examination even when a cancer is palpable, with adverse effects if
      biopsy is delayed.

PMID- 1990739
TI  - Physician compliance: improving skills in preventive medicine practices.
AB  - Physicians may not comply with all of the preventive medicine recommendations
      issued by recognized medical consensus groups. Compliance with recommendations
      for mammography, Papanicolaou tests and smoking cessation counseling is
      particularly important because of the potential to save lives. Compliance failure
      rates are often underestimated, in part because of misconceptions about the
      nature of physician compliance. An understanding of the difficulty in accurately
      estimating compliance and an awareness of the factors that affect compliance are
      fundamental to improving the delivery of preventive services.

PMID- 1990740
TI  - New approaches to improve diabetes control.
AB  - Knowledge about diabetes mellitus and its management has steadily increased since
      the discovery of insulin in 1921. Specific therapies for both type I and type II
      diabetes have resulted in greater normalization of plasma glucose levels.
      Information obtained from self-monitoring of blood glucose levels has given
      physicians a firmer base on which to make management decisions concerning the
      safe control of diabetes.

PMID- 1990741
TI  - Comparative clinical pharmacology of calcium channel blockers.
AB  - Calcium channel blockers are effective antihypertensive agents, both as initial
      monotherapy and in combination with other antihypertensive agents. These drugs
      are also effective in the treatment of chronic, stable angina, variant angina and
      supraventricular arrhythmias. Drugs in this class have different affinities for
      calcium channels in vascular smooth muscle, cardiac muscle, cardiac sinus and
      atrioventricular node. They are all useful in hypertension and angina, but only
      verapamil and diltiazem are also useful in the control of heart rate and
      supraventricular arrhythmias. Nimodipine may control vascular spasm following
      subarachnoid hemorrhage. Calcium channel blockers have also been used in the
      treatment of migraine headache and Raynaud's phenomenon.

PMID- 1990742
TI  - NIAMSD releases consensus report on osteoporosis.

PMID- 1990743
TI  - Cruzan in context.

PMID- 1990745
TI  - Acute complications of percutaneous transluminal coronary angioplasty for total
      occlusion.
AB  - The incidence of major complications after percutaneous coronary angioplasty
      (PTCA) of a totally occluded artery was assessed retrospectively. A total of 1649
      PTCA procedures were analyzed. After exclusion of procedures for acute myocardial
      infarction or total occlusion that resulted from restenosis, 90 patients were
      selected. Forty-four patients (49%) had stable angina and 46 (51%) had unstable
      angina. The estimated duration of occlusion was 87 +/- 78 days in patients with
      stable angina, as compared with 10 +/- 8 days in patients with unstable angina (p
      less than 0.001). Abrupt vessel closure during PTCA occurred only in patients
      with unstable angina (0% versus 17%, p less than 0.05). The major complication
      rate was 2.5% in the stable angina group, and 20% in unstable angina group (p
      less than 0.01). This rate was also significantly higher than the complication
      rate of 8% observed in 442 procedures that were performed during the same period
      in patients with the unstable angina and nonocclusive stenosis (p less than
      0.01). Patients with unstable angina who undergo PTCA of a totally occluded
      artery represent a subset of high risk for major complications.

PMID- 1990744
TI  - Relation between flow grade after thrombolytic therapy and the effect of
      angioplasty on left ventricular function: a prospective randomized trial.
AB  - Recent intervention trials during myocardial infarction demonstrated no benefit
      from emergency angioplasty after thrombolytic therapy when compared with either
      delayed percutaneous transluminal coronary angioplasty (PTCA) or a conservative
      strategy. However, it is possible that subgroups of patients may benefit from
      early intervention with angioplasty. We performed a prospective randomized trial
      in patients with a patent infarct-related artery after thrombolytic therapy to
      determine whether initial flow grade is related to infarct-zone function and
      whether patients with ineffective reperfusion (greater than 90% stenosis or
      Thrombolysis in Myocardial Infarction [TIMI] flow less than or equal to 2) might
      benefit from immediate PTCA. Thrombolytic therapy was administered to 170
      patients at a mean of 2.1 +/- 0.5 hours after onset of myocardial infarction. A
      patent infarct-related artery that was suitable for angioplasty was present in 89
      patients who comprised the study group; after randomization, 47 of 50 patients
      with a patent infarct-related artery had successful emergency PTCA 3.8 +/- 1.5
      hours after onset of symptoms, and 39 were scheduled for delayed (18 to 48-hour)
      PTCA. Reocclusion occurred before the scheduled (delayed) procedure in eight
      patients (20.5%), and was symptomatic in six. Infarct-region function (by the
      centerline method) measured initially, before discharge, and at 4 months was
      similar in both groups; improvement was significant (p less than 0.001) at
      discharge when compared with initial values with no further change at 4 months.
      However, patients with ineffective reperfusion had greater hypokinesia initially
      (p less than 0.05) compared with those with effective reperfusion (less than or
      equal to 90% stenosis plus TIMI flow 3). Moreover, independent of the timing of
      PTCA, improvement was greater before discharge in patients with ineffective
      reperfusion (p less than 0.05) with a trend also evident at 4 months.
      Importantly, 42 of 51 patients (82%) with a residual lumen less than 0.4 mm after
      thrombolysis had some improvement in function at discharge; this compared with a
      previous study in which patients with a similar degree of stenosis (without PTCA)
      had no improvement. Moreover, reocclusion occurred before scheduled (delayed)
      PTCA in 37% of patients with greater than 90% stenosis compared with only 5% in
      those with less than or equal to 90% stenosis (p = 0.02). Thus flow grade is an
      important determinant of myocardial function in patients with a patent artery
      after thrombolytic therapy and is predictive both of improvement in wall motion
      after PTCA and early reocclusion.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1990746
TI  - Stunned myocardium and myocardial collagen damage: differential effects of single
      and repeated occlusions.
AB  - It has been suggested that collagen loss and damage is responsible for the
      dysfunction seen in stunned myocardium. To test this hypothesis we compared
      collagen in canine hearts stunned by repeated occlusion with collagen in hearts
      stunned by a single occlusion. Regional contractile function was equally
      depressed in both groups: segment shortening at 1 hour after reperfusion averaged
      37% +/- 9% versus 32% +/- 9% of preocclusion values in repeated and single
      occlusion models, respectively. Midmyocardial collagen content was not different
      in either single occlusion (10.5% +/- 0.4%) or repeated occlusion models (9.5% +/
      0.7%) when compared with nonischemic hearts (8.5 +/- 0.8%). Collagen damage,
      which was revealed with polarized light microscopy, was seen in 5 of 6 dogs after
      repeated occlusion but was not apparent after a single occlusion. Thus although
      both models of stunned myocardium produce similar dysfunction, there was no
      apparent collagen loss. Furthermore, collagen damage was only seen after repeated
      occlusion. Therefore it appears unlikely that collagen damage is a primary
      mechanism of stunned myocardium.

PMID- 1990748
TI  - Complete left main coronary artery occlusion: angiographic evaluation of
      collateral vessel patterns and assessment of hemodynamic correlates.
AB  - An angiographic study of eight patients with total occlusion of the left main
      coronary artery identified six patients with chronic occlusion and two with acute
      complete occlusion. In each of six patients, there were two to six different
      intercoronary collateral pathways. Altogether, a total of 13 specific collateral
      channels were recognized. One patient had evidence of unique homocollaterals
      represented by enlarged vasa vasorum, which created a vascular cuff that
      surrounded a totally obstructed left main artery. The ventricular function and
      hemodynamic parameters in these patients not only depend on the collateral
      vessels but may also be affected by the severity of coronary artery disease in
      the artery that supplies collaterals.

PMID- 1990747
TI  - Coronary sinus occlusion: effect on ischemic left ventricular dysfunction and
      reactive hyperemia.
AB  - Pressure-controlled intermittent coronary sinus occlusion (PICSO) has been shown
      to reduce experimental infarct size. To examine the role of PICSO in limiting the
      consequences of brief ischemia on left ventricular function, we studied the
      effect of PICSO in nine open-chest anesthetized dogs. PICSO was performed using a
      pump-inflated, balloon-tipped catheter in the coronary sinus until coronary sinus
      occlusion pressure reached a plateau (10 +/- 3 seconds). The balloon was then
      rapidly deflated (2 seconds) and the cycle was repeated. Regional left
      ventricular function in the ischemic zone was assessed by sonomicrometry.
      Coronary blood flow was measured with a flow probe around the left anterior
      descending artery (LAD) proximal to an occluding suture. Measurements were
      obtained at baseline, during a 3-minute LAD occlusion, and for 10 minutes of
      reperfusion. In an additional five dogs, this sequence was repeated during an
      infusion of adenosine at a dose that abolished reactive hyperemia following LAD
      occlusion. The addition of PICSO beginning 15 minutes prior to ischemia and
      continuing throughout LAD occlusion and reperfusion did not prevent, reduce, or
      shorten ischemic left ventricular dysfunction. PICSO uniformly blunted reactive
      hyperemia during reperfusion. However, PICSO also reduced coronary blood flow
      during maximal vasodilatation achieved by adenosine infusion prior to LAD
      occlusion. Therefore, it is likely that PICSO decreases reactive hyperemia due to
      mechanical factors arising from venous engorgement rather than by reducing the
      ischemic stimulus causing vasodilation.

PMID- 1990749
TI  - Factors associated with recurrent myocardial infarction within one year after
      acute myocardial infarction.
AB  - In a large population of patients (n = 3666) who were discharged from the
      hospital after acute myocardial infarction and followed up for 1 year, factors
      associated with recurrent nonfatal (n = 171) or fatal (n = 74) infarction were
      identified. Also, the effects of combining various end points (recurrent nonfatal
      or fatal infarction and other cardiac death) in multivariate analyses, a practice
      common in many small studies that evaluate the predictive-value of various
      treatments or special tests, was examined. In univariate analyses, patients with
      nonfatal recurrent infarction did not differ with respect to age or gender from
      infarct-free survivors, but they more often had a history of previous myocardial
      infarction, congestive heart failure, angina pectoris, and diabetes; more severe
      pulmonary congestion was present on chest x-ray during the admission, and a non-Q
      wave index infarction was more frequent. Patients with either a fatal or nonfatal
      recurrent infarction had more angina pectoris during follow-up (55% to 60%)
      compared with 27% in event-free survivors and 31% in patients who died of other
      cardiac causes in whom this factor could be assessed before death. In
      multivariate analyses, historical and clinical prognostic factors were ranked
      differently for fatal or nonfatal reinfarction and other cardiac causes of death;
      angina pectoris at follow-up was highly related to recurrent infarction (fatal or
      nonfatal), along with a history of diabetes, and a non-Q wave index infarction.
      These factors were not independently related to other causes of cardiac
      death.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1990750
TI  - Dilatation of the left ventricular cavity on dipyridamole thallium-201 imaging: a
      new marker of triple-vessel disease.
AB  - To investigate the significance and mechanism of dilatation of the left
      ventricular cavity on dipyridamole thallium-201 imaging, we performed both
      dipyridamole thallium-201 imaging and dipyridamole radionuclide angiography on 83
      patients with known angiograms. The dipyridamole/delayed ratio of the left
      ventricular dimension from the thallium-201 image was defined as the left
      ventricular dilatation ratio (LVDR). An LVDR greater than the mean + two standard
      deviations in patients without coronary artery disease was defined as abnormal.
      Twenty-two of 83 patients showed an abnormal LVDR, and 18 of the 22 patients
      (82%) had triple-vessel disease. By defect and washout analysis, the sensitivity
      and specificity for correctly identifying the patients as having triple-vessel
      disease was 72% and 76%, respectively, whereas LVDR had a sensitivity of 72% and
      a specificity of 93%. When LVDR was used in combination with the defect and
      washout criteria, sensitivity increased to 84% without a loss of specificity. In
      those 22 patients with abnormal LVDRs, end-diastolic volume measured by
      radionuclide angiography did not change after dipyridamole infusion. Dilatation
      of the left ventricular cavity on dipyridamole thallium-201 imaging reflected
      relative subendocardial hypoperfusion induced by dipyridamole rather than actual
      chamber enlargement. The LVDR was moderately sensitive and highly specific for
      triple-vessel disease and provided complementary information to dipyridamole
      thallium-201 imaging.

PMID- 1990751
TI  - Percutaneous balloon valvotomy for patients with mitral stenosis: initial and
      follow-up results.
AB  - Percutaneous double balloon mitral valvotomy (PMV) was performed in 25 patients
      with severe mitral stenosis who were followed for at least 6 months after the
      procedure. There were 22 women and 3 men, with a mean age of 51 +/- 14 years
      (range, 27 to 74). Hemodynamic and angiographic findings were evaluated before
      and after PMV and clinical status was assessed at follow-up. There was a
      significant decrease in mitral gradient following PMV, from 15.4 +/- 5.1 to 5.0
      +/- 2.6 mm Hg (p less than .0001); an increase in cardiac output, from 4.6 +/-
      1.1 to 5.2 +/- 1.1 L/min (p less than .01); and an increase in calculated mitral
      valve area, from 0.9 +/- 0.2 to 2.2 +/- 0.6 cm2 (p less than 0.0001). Mitral
      regurgitation developed or increased in severity in six patients (24%). At the
      time of follow-up (mean, 12 +/- 5 months), three patients required elective
      mitral valve replacement for symptomatic mitral regurgitation and 91% (20 of 22)
      of the remaining patients had continued improvement in functional class. PMV can
      safely be performed in properly selected patients with symptomatic mitral
      stenosis with good immediate and follow-up results.

PMID- 1990752
TI  - Value and limitations of Doppler pressure half-time in quantifying mitral
      stenosis: a comparison with micromanometer catheter recordings.
AB  - The purpose of this study was to compare the Doppler and catheterization pressure
      half-time methods of estimating mitral valve area with valve areas obtained by
      the Gorlin equation in a group of patients with clinically significant mitral
      stenosis. Data were analyzed from 67 consecutive patients who were undergoing
      continuous-wave Doppler examination and catheterization with micromanometer
      catheters. Doppler pressure half-time was calculated as the interval between peak
      transmitral velocity and velocity divided by the square root of 2, as measured
      from the outer border of the spectral envelope. Doppler mitral valve area (MVA)
      was obtained with the equation: MVA = 220 divided by pressure half-time. For
      catheterization data, the pressure half-time was measured directly from
      simultaneously recorded left ventricular and left atrial pressure (18 patients)
      or pulmonary capillary wedge pressure (49 patients). The catheterization half
      time was taken as the time required for the peak pressure gradient to fall to one
      half of the initial value. Calculations of the mitral valve area at
      catheterization were obtained by the Gorlin equation with pressure gradient and
      cardiac output determinations. Mitral valve area as determined by the Gorlin
      equation for all cases ranged from 0.4 to 2.0 (mean = 1.03 +/- 0.37) cm2. Linear
      regression analysis that compared cardiac catheterization and Doppler half-times
      yielded r = 0.68. For the subgroup of patients with sinus rhythm, the correlation
      improved to r = 0.76.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1990753
TI  - Effect of severe pulmonary hypertension on the calculation of mitral valve area
      in patients with mitral stenosis.
AB  - We studied 50 consecutive patients with mitral valve stenosis (MS) by cardiac
      catheterization and Doppler echocardiography to assess whether the presence of
      severe pulmonary hypertension affected the calculation of valve area by Doppler
      pressure half-time method and by the Gorlin formula using pulmonary capillary
      wedge pressure as an index of left atrial pressure. Patients with severe mitral
      regurgitation were excluded. In patients with pulmonary artery systolic pressure
      (PAS) less than 70 mm Hg (n = 33), there was good correlation between the mitral
      valve area derived from Doppler echocardiography and from cardiac catheterization
      (r = 0.85). However, in patients with PAS greater than or equal to 70 mm Hg (n =
      17), this correlation was not as good (r = 0.57). In these 17 patients, the
      Gorlin formula tended to underestimate the valve orifice area (mean valve area
      0.85 +/- 0.49 and 1.06 +/- 0.46 cm2 by catheterization and by Doppler
      respectively, p = NS). Direct measurement of the valve area by two-dimensional
      echocardiography was possible in 12 of the 17 patients and correlated well with
      Doppler values (r = 0.91). Hence in the presence of severe pulmonary
      hypertension, Doppler pressure half-time estimation of mitral valve area is more
      accurate than is catheterization-derived valve area, using the wedge pressure and
      the Gorlin formula.

PMID- 1990754
TI  - Study of the influence of left bundle branch block on the signal-averaged
      electrocardiogram: a qualitative and quantitative analysis.
AB  - To study the influence of left bundle branch block (LBBB) on the signal-averaged
      electrocardiogram (SAECG), quantitative and qualitative analyses of SAECG
      parameters were undertaken in 48 patients with electrocardiographic evidence of
      intrinsic LBBB and in 39 patients with a "normal" surface QRS duration (less than
      120 msec) who underwent right ventricular pacing-induced LBBB. We assumed pacing
      of the right ventricular apex to be a suitable model of this conduction defect.
      Sustained monomorphic ventricular tachycardia (SMVT) was inducible in 16 of 48
      patients with intrinsic LBBB and in 23 of 39 patients with pacing-induced LBBB.
      Utilizing a filter setting of 25 to 250 Hz, late potentials were defined as a
      total filtered QRS duration greater than or equal to 120 msec, a root mean square
      voltage in the terminal 40 msec (RMS 40) of less than or equal to 25 microV, and
      the duration of signals less than 40 microV (LAS 40) of greater than or equal to
      38 msec. Only RMS 40 and LAS 40 criteria were used in patients with LBBB.
      Prolongation of LAS 40 and fragmentation of signals in the terminal portion of
      the filtered QRS were characteristic of all patients with LBBB aberration. Of
      those patients with intrinsic LBBB, the mean total filtered QRS duration, RMS 40,
      and LAS 40 for inducible and noninducible patients were significantly different
      (170 +/- 28, 16 +/- 10, 55 +/- 24, and 153 +/- 18 msec, 25 +/- 10 microV, 33 +/-
      16.9 msec; p = 0.04, 0.009, and 0.007, respectively). Noninducible patients with
      a normal QRS duration demonstrated a 60% decrement in the mean RMS 40 value
      during pacing-induced LBBB. These changes resulted in a 59% false positive
      incidence of late potentials during pacing-induced LBBB. This correlated with a
      similarly low mean RMS 40 value in patients with intrinsic LBBB and no inducible
      SMVT, hence giving rise to a false positive incidence of late potentials of 63%.
      Since "standard" RMS 40 and LAS 40 criteria resulted in low specificity and
      positive predictive value, new parameters were selected and analyzed. The
      combination of RMS 40 less than or equal to 17 microV plus LAS 40 greater than or
      equal to 55 msec yielded the best overall statistical result, with a sensitivity,
      specificity, and total predictive accuracy of 69%, 81%, and 77%, respectively. IN
      CONCLUSION: (1) A reduction of RMS 40, prolongation of LAS 40, and fragmentation
      of signals in the terminal portion of the filtered QRS are characteristics of
      LBBB.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1990755
TI  - Short-term variability of ventricular arrhythmia and rapid assessment of drug
      efficacy.
AB  - Statistical criteria for suppression and aggravation of ventricular arrhythmia
      were defined by means of 50 short-term drug tests performed in 24 patients. Each
      patient's spontaneous variability (SV) was evaluated by linear regression
      analysis of hour-to-hour changes in ectopy during 24- to 48-hour Holter
      monitoring. The response to a single oral dose of disopyramide, 300 mg,
      flecainide, 200 mg, and propafenone, 450 mg, was measured during a trial lasting
      4 hours. Lidocaine was administered intravenously in incremental doses of up to 4
      mg/min and was evaluated over 3 hours. Threshold values of ventricular arrhythmia
      corresponding to 95% confidence limits were calculated from baseline recordings
      and were used to ascertain the likelihood of a true drug effect. The minimum
      decrease in hourly ectopy indicating arrhythmia suppression averaged 90.9%, while
      an increase of at least 947% was required for a proarrhythmic effect. When these
      efficacy criteria were applied, 16 of 50 short-term tests revealed no drug
      effect. In contrast, when a 70% threshold derived from studies of daily
      variability was employed, only 7 of 50 trials were negative. Thus individual
      determination of hourly arrhythmia variability yields more stringent criteria
      than extrapolation from day-to-day spontaneous variation.

PMID- 1990756
TI  - The effect of quinidine and mexiletine on the adaptation of ventricular
      refractoriness to an increase in rate.
AB  - The purpose of this study was to determine the effects of quinidine and
      mexiletine on the adaptation of ventricular refractoriness to a change in heart
      rate. The ventricular effective refractory period was measured at a basic drive
      cycle length of 500 msec with basic drive train durations of two beats, eight
      beats, 20 beats and 3 minutes. The ventricular refractory periods were measured
      in the baseline state and after oral treatment with quinidine or mexiletine in 20
      subjects each. In the baseline state, there was progressive shortening of the
      ventricular refractory period as the drive train duration increased from two
      beats to 3 minutes. Quinidine prolonged refractoriness by 5% (p less than 0.001)
      at each drive train duration. Mexiletine did not affect the ventricular effective
      refractory period at any of the drive train durations. In a control group of 20
      subjects, there were no significant differences between two determinations of
      refractoriness at each basic drive train duration. In conclusion, neither
      quinidine nor mexiletine affect the adaptation of ventricular refractoriness to
      an increase in rate. Although the ventricular effective refractory period
      measured with a conventional basic drive train duration of eight beats is often
      more than 20 msec longer than the actual ventricular effective refractory period
      measured with a drive train duration of 3 minutes, the effects of quinidine and
      mexiletine on the conventionally measured ventricular effective refractory period
      accurately reflect the effects of these drugs on the actual ventricular effective
      refractory period.

PMID- 1990757
TI  - Effect of hyperkalemia on experimental myocardial depression by verapamil.
AB  - Three patients with systemic hypotension and sinus bradycardia that were
      initially refractory to conventional therapy responded well to intravenous
      calcium administration. Two-dimensional echocardiography revealed immediate
      reversal of severe left ventricular dysfunction after intravenous administration
      of calcium in two instances. Common factors were hyperkalemia and verapamil
      therapy. This interaction was examined further by evaluation of contractility,
      heart rate, and arterial blood pressure in anesthetized dogs. Controls (n = 9)
      received saline infusion, and a second group (n = 10) received saturated
      potassium chloride (approximately 0.2 ml/min intravenously). In control dogs,
      administration of verapamil (1195 +/- 181 micrograms/kg intravenously) reduced
      systemic arterial pressure from 113 +/- 7 mm Hg to 74 +/- 5 mm Hg, and heart rate
      from 147 +/- 9 beats/min to 86 +/- 11 beats/min. Potassium chloride infusion
      alone increased blood [K+] from 3.4 +/- 0.1 to 6.2 +/- 0.2 mEq/L, but was without
      hemodynamic effects. In hyperkalemic dogs, a significantly lower dose of
      verapamil (428 +/- 42 micrograms/kg intravenously) reduced systemic arterial
      pressure from 102 +/- 8 mm Hg to 36 +/- 4 mm Hg, and heart rate from 150 +/- 5
      beats/min to 104 +/- 15 beats/min. Myocardial contractile function was examined
      with right ventricular isometric contractile force and left ventricular segment
      length changes. In normokalemic and hyperkalemic groups, contractility was
      decreased by verapamil. Effects of verapamil on arterial pressure and
      contractility could be reversed significantly by administration of calcium, 0.4
      mEq/kg intravenously. The present results support the theory that the negative
      hemodynamic effects of verapamil may be exaggerated to a harmful degree by
      concomitant hyperkalemia. These adverse events may be reversed by calcium
      administration.

PMID- 1990758
TI  - Gender differences in the systolic blood pressure response to exercise.
AB  - Previous work has shown a gender difference in the normal cardiac response to
      exercise. Men had significantly higher absolute systolic blood pressure responses
      at 50%, 75%, and 100% peak heart rate on all modalities (p less than 0.05). This
      difference is absent when systolic blood pressure is adjusted for body surface
      area, is reduced when adjusted for body weights, and is reversed when systolic
      blood pressure is adjusted for lean body mass. The influence of gender on the
      systolic blood pressure response to dynamic exercise was independent of exercise
      modality. Men had a higher systolic blood pressure in spite of the fact that they
      had similar sympathetic nervous system response as indicated by urinary
      norepinephrine excretion. Gender differences in systolic blood pressure responses
      were altered when adjusted for body weight, body surface area, and lean body
      mass.

PMID- 1990759
TI  - Mechanism for depressed cardiac function in left ventricular volume overload.
AB  - To assess the effects of left ventricular chamber volume on the mechanism of
      changes in left ventricular developed pressure we performed phosphorous-31
      nuclear magnetic resonance spectroscopy, hydrogen-1 nuclear magnetic resonance
      spectroscopy with a shift reagent, two-dimensional echocardiography, atomic
      absorption spectrophotometry, microsphere analysis, and surface fluorometry on
      isovolumic isolated perfused rat hearts with incremental intraventricular balloon
      volumes, while left ventricular pressure was concurrently monitored. A three
      phasic response of developed pressure was noted: 0 to 100 microliters balloon
      volumes resulted in an increase in developed pressure, whereas developed pressure
      remained constant at 250 microliters and fell at 400 microliters. Oxygen
      consumption and [Ca2+]i transients followed the same pattern as developed
      pressure and coronary flow. Intraventricular volumes of 250 microliters or
      greater (a volume overload) caused endocardial ischemia, a greater decrease in
      extracellular versus intracellular water, thinning of the left ventricular free
      wall, and an increase in chamber size. Mechanical pressure on the tissue, induced
      by the volume overload, caused ischemia as further evidenced by (1) a negative
      effect on developed pressure, (2) a decrease in [Ca2+]i transients, (3) a [Ca2+]i
      overload, (4) a moderate decrease in the phosphorylation potential, and (5) an
      increase in the oxidation-reduction state (nicotinamide-adenine dinucleotide).
      The high intracellular calcium associated with volume overload may have been due
      to both compression and ischemia, which leads to an increased number of cross
      bridges in rigor, a high end-diastolic pressure, and an increase in wall stress.

PMID- 1990760
TI  - Flosequinan: a vasodilator with positive inotropic activity.
AB  - Flosequinan is an oral arterial and venous vasodilator that is currently under
      investigation for the treatment of congestive heart failure. The effects of
      flosequinan on ventricular performance and myocardial contractility were studied
      in 10 patients with severe congestive heart failure during right and left cardiac
      catheterization. Sixty minutes after a 100 mg oral dose of flosequinan, the peak
      rate of rise in left ventricular pressure (dP/dt) increased from 940 +/- 180 to
      1050 +/- 240 mm Hg/sec (p less than 0.05), while left ventricular end-diastolic
      pressure decreased from 32 +/- 5 to 26 +/- 8 mm Hg (p less than 0.05), and
      cardiac index increased (2.1 +/- 0.4 to 2.3 +/- 0.5 L/min/m2, (p less than 0.05).
      The mean pulmonary artery pressure and vascular resistance decreased from 40 +/-
      8 to 33 +/- 12 mm Hg (p less than 0.05) and from 330 +/- 240 to 290 +/- 170 dyne
      sec/cm5 (p less than 0.05), respectively. Heart rate, mean aortic pressure, right
      atrial pressure, systemic vascular resistance, and serum norepinephrine levels
      did not change significantly. The increase in left ventricular peak dP/dt that
      was concomitant with a decrease in left ventricular end-diastolic pressure, and
      no change in systemic arterial pressure or sympathetic tone, argue for a direct
      positive inotropic effect of flosequinan.

PMID- 1990761
TI  - Dietary taurine deficiency and dilated cardiomyopathy in the fox.
AB  - Taurine deficiency has been implicated as a potential cause of dilated
      cardiomyopathy. However, the relationship between taurine and myocardial function
      is presently unclear. The purpose of this study was to determine whether dilated
      cardiomyopathy in the fox is associated with dietary taurine deficiency. A total
      of 68 foxes from farms with a history of death caused by dilated cardiomyopathy
      and 14 foxes from a farm with no history of dilated cardiomyopathy were studied.
      Dilated cardiomyopathy was diagnosed by echocardiography in 48% of the foxes from
      one farm with a positive history and in none of the foxes from the control farm.
      Foxes less than 9 months of age were more commonly affected than older foxes (p =
      0.03). Plasma taurine concentrations were significantly less (p less than 0.01)
      in foxes that had dilated cardiomyopathy (26.8 +/- 16.4 nmol/ml) than in the
      control foxes (99.3 +/- 60.2 nmol/ml). A significantly higher (p less than 0.01)
      incidence of dilated cardiomyopathy was present in foxes with a history of a
      sibling or offspring that died of dilated cardiomyopathy than in foxes without a
      family history of cardiac death. In one fox with dilated cardiomyopathy that was
      tested, the myocardial taurine concentration was lower (1.7 mumol/gm wet weight)
      than that of control foxes (7.3 +/- 1.6 mumol/gm wet weight). Hepatic
      cysteinesulfinic acid decarboxylase activity was significantly less (p less than
      0.001) in foxes with dilated cardiomyopathy (0.97 +/- 0.2 nmol/mm.mg protein)
      than in control foxes (2.11 +/- 0.07 nmol CO2/mm.mg protein).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1990762
TI  - Changes in left ventricular systolic function that accompany rejection of the
      transplanted heart: a serial radionuclide assessment of fifty-three consecutive
      cases.
AB  - To examine the functional changes that accompany the development of rejection of
      the orthotopically transplanted heart, radionuclide ventriculograms, right heart
      catheterizations, and endomyocardial biopsies were performed at weekly intervals
      during the posttransplantation hospitalization of 53 consecutive transplant
      recipients. Left ventricular ejection fraction decreased in those (n = 10) who
      had sequential biopsies that changed from no rejection to moderate rejection (63%
      +/- 7% to 57% +/- 7% respectively, p = 0.007). There was an associated decrease
      in the peak ejection rate (4.4 +/- 1.0 to 3.9 +/- 0.8 end-diastolic volumes per
      second, p = 0.008) and an increase in the time to peak ejection rate (137 +/- 27
      msec to 153 +/- 20 msec, p = 0.004) that accompanied the development of
      rejection. There was a similar decrease in left ventricular ejection fraction in
      those (n = 9) who had sequential biopsies that changed from no rejection to mild
      rejection (63% +/- 6% to 59% +/- 8%, p = 0.009). Only two of 19 patients whose
      biopsies changed from no rejection to either mild or moderate rejection did not
      have an associated decrease in ejection fraction. In patients who had a biopsy
      that showed definite rejection, which was then followed by histologic resolution
      after treatment (n = 11), left ventricular ejection fraction increased from 56%
      +/- 8% to 61% +/- 8%, p = 0.03. There were no significant changes in any of the
      parameters of diastolic function or in any of the hemodynamic parameters
      measured, which were associated with either the development or resolution of
      rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1990763
TI  - Prosthetic valves in children and adolescents.
AB  - The purpose of this paper is to present the short- and long-term results of
      prosthetic valve replacement in children. During a 7-year period that ended in
      April 1985, 186 children, ages 1 to 20 years, underwent valve replacement; there
      were 55 (30%) aortic valve replacements, 95 (51%) mitral valve replacements, and
      36 (19%) multiple valve replacements. Ninety-four percent of the lesions were
      rheumatic in origin, 4% were congenital, and 2% were infectious. Of 223 valves
      replaced, 175 (78%) were mechanical valves and 48 (22%) were heterografts; the
      latter were in the mitral position in all but three patients. Surgical mortality
      rates were 3.6%, 4.2%, and 19.4% respectively for aortic valve, mitral valve, and
      multiple valve replacements. Five-year actuarial survival was 91% for aortic
      valve replacement, 82% for mitral valve replacement and 60% for multiple valve
      replacement. Major events included reoperation in 34 (with three deaths),
      progressive myocardial failure that led to death in 10, sudden unexpected death
      in two, thromboembolic complications in 19 (death in five), subacute bacterial
      endocarditis in five (two deaths), and bleeding that required transfusion in two
      patients. Five-year complication-free actuarial survival rates were 83% for
      aortic valve replacement, 63% for mitral valve replacement, and 57% for multiple
      valve replacement. The respective five-year complication-free survival rates were
      83%, 48%, and 43%. Significant morbidity and mortality rates are associated with
      valve replacement. Therefore every effort should be made to preserve the native
      valve by plastic reparative procedures. When prosthetic replacement of mitral
      valve is contemplated, our data would suggest that heterografts should not be
      inserted in children 15 years of age or younger, although heterografts may be
      used in children over 15 years of age with the expectation of valve survival
      comparable to that of mechanical valves. When complications that are associated
      with anticoagulant therapy were reviewed, platelet inhibiting drugs seem quite
      satisfactory in patients with aortic valve replacement; patients with mitral
      valve replacement seem to require warfarin therapy, and warfarin must be used in
      patients with multiple valve replacement to reduce the risk of thromboembolic
      complications.

PMID- 1990764
TI  - Beat-to-beat detection of ventricular late potentials with high-resolution
      electrocardiography.
AB  - To detect dynamic changes of VLPs we developed a low-noise, HR-ECG with a gain of
      10(5)-10(6)X. This system allows the beat-to-beat detection of low-amplitude
      signals at the bedside in a nonshielded room without any averaging process.
      Analysis was performed in 39 normal subjects (group A: 27 men, 12 women, mean
      age, 28 +/- 8 years), in 98 patients with coronary artery disease without
      documented sustained ventricular tachycardia (group B: 86 men, 12 women, mean
      age, 59 +/- 10 years) and in 41 patients coronary artery disease with sustained
      monomorphic ventricular tachycardia (group C: 36 men, 5 women; mean age 63 +/- 9
      years). Comparison was made with time-domain signal-averaging (SA-ECG) in all
      cases at the same electrode position and with identical band-pass filtering. In
      group A no VLPs were detected; the total filtered QRS duration was 84 +/- 8 msec
      (mean +/- SD), and the time interval during which the terminal QRS did not exceed
      40 microV (I-40) was less than 30 msec in all cases (mean, 17 +/- 6 msec). In
      group B, VLPs were detected by HR-ECG in 34 of 98 patients (35%); the total QRS
      duration was 102 +/- 16 msec (mean +/- SD, p less than 0.01 vs group A), and the
      I-40 was 29 +/- 13 msec (mean +/- SD, p less than 0.01 vs (group A). In group C,
      VLPs were detected by HR-ECG in 38 of 41 patients (93%); the total QRS duration
      was 123 +/- 22 msec (mean +/- SD, p less than 0.01 vs group A and group B), and
      the I-40 was 40 +/- 14 msec (mean +/- SD, p less than 0.01 vs group A and group
      B). Concordant results between HR-ECG and SA-ECG were observed in 91% of the
      cases (59 positive and 103 negative results). Late potentials that exhibited
      dynamic variations were detected by HR-ECG alone in 13 cases, and very low
      amplitude VLPs were detected by SA-ECG alone in three cases. In conclusion, the
      present study demonstrates the feasibility of body-surface recording of VLPs on a
      beat-to-beat basis, without any averaging process, at the bedside in a
      nonshielded room. This new approach may allow the study of dynamic changes of
      VLPs during spontaneous ventricular arrhythmias or ischemia.

PMID- 1990765
TI  - Is hyperglycemia associated with cardiovascular disease? The Framingham Study.
AB  - The association of nonfasting blood glucose levels with CVD incidence was
      determined prospectively in 1382 men and 2094 women aged 45 to 84 years
      participating in the Framingham Heart Study. For this study, all patients were
      classified in 1970 as diabetic or nondiabetic. Every 2 years they were examined,
      categorized according to causal blood glucose samples obtained at the clinic
      visit, reclassified for development of CVD and diabetes mellitus, and followed 10
      years for CVD. During the follow-up period, 350 men and 369 women developed CVD.
      Age-adjusted CVD rates were positively associated with glucose levels in
      nondiabetic women who did not develop diabetes during follow-up. No such
      associations were seen in men. Multivariate analyses confirmed the independent
      association of blood glucose levels with later CVD in nondiabetic women. This
      study shows that hyperglycemia in the original Framingham cohort is an
      independent risk factor for CVD in nondiabetic women, but not among men.

PMID- 1990766
TI  - Stunned myocardium following coronary spasm.

PMID- 1990767
TI  - Sensor-initiated termination of pacemaker-mediated tachycardia in a DDDR
      pacemaker.

PMID- 1990768
TI  - Paroxysmal AV block with ventricular standstill precipitated by atrial flutter
      during acute myocardial infarction.

PMID- 1990769
TI  - Antiarrhythmic therapy guided by programmed electrical stimulation in cardiac
      sarcoidosis with ventricular tachycardia.

PMID- 1990770
TI  - Sotalol-induced torsades de pointes successfully treated with hemodialysis after
      failure of conventional therapy.

PMID- 1990771
TI  - Excessive secretion of vasopressin during vasovagal reaction.

PMID- 1990772
TI  - Exertional syncope in aortic stenosis: evidence to support inappropriate left
      ventricular baroreceptor response.

PMID- 1990773
TI  - Extreme obstruction to left ventricular outflow by a bioprosthesis in the mitral
      valve position.

PMID- 1990774
TI  - Cessation of gastrointestinal bleeding from angiodysplasia after surgery for
      idiopathic hypertrophic subaortic stenosis.

PMID- 1990775
TI  - Reversible catecholamine-induced cardiomyopathy.

PMID- 1990776
TI  - A variant of the scimitar syndrome with stenosed drainage of the inferior vena
      cava.

PMID- 1990777
TI  - Protein-losing enteropathy following the Fontan operation: resolution with
      prednisone therapy.

PMID- 1990778
TI  - The use of extracorporeal membrane oxygenation in critically ill neonates with
      Ebstein's anomaly.

PMID- 1990779
TI  - Transesophageal Doppler analysis of pulmonary venous flow in cardiac transplant
      recipients.

PMID- 1990780
TI  - Risk stratification in survivors of acute myocardial infarction: routine cardiac
      catheterization and angiography is a reasonable approach in most patients.
AB  - Noninvasive risk assessment in survivors of AMI can effectively subdivide
      patients into groups with differing risk profiles after hospital discharge, but
      some patients at risk for late death or recurrent AMI may be incorrectly
      identified; data from cardiac catheterization and angiography provide
      complementary and generally more powerful prognostic information. Many patients
      may derive particular benefit from early cardiac catheterization and angiography,
      including: (1) patients with AMI complicated by recurrent myocardial ischemia,
      congestive heart failure, and/or complex ventricular arrhythmias; (2) patients
      with abnormal or inconclusive results of noninvasive testing or those patients
      unable to perform an exercise test; (3) patients with abnormal left ventricular
      global systolic function and those with increased left ventricular end-systolic
      volume; (4) "young" patients (younger than 50 years of age?); (5) older patients
      (older than 65 to 70 years of age?); (6) patients with non-Q wave AMI; and (7)
      patients who are receiving thrombolytic therapy. Performance of early cardiac
      catheterization and angiography in virtually all survivors of AMI, with selective
      use of appropriate noninvasive tests, may provide a more efficacious means of
      risk assessment after AMI; if all tests are performed judiciously, the cost of
      such an approach need not be excessive. A combination of invasive and selected
      noninvasive tests probably provides optimal information. The risks to the routine
      performance of diagnostic cardiac catheterization and angiography in all
      survivors of AMI are: (1) adequate care and attention may not be paid to proper
      performance of the procedure(s) and to detailed and proper analyses of the data;
      (2) the need for additional noninvasive testing in selected patients may be
      ignored; and most importantly, (3) premature or unnecessary revascularization
      procedures may be performed subsequently. For optimal patient care, the clinician
      must obtain all necessary data, avoid unnecessary and repetitive tests, know the
      accuracy of individual tests at his or her own facility, interpret all data in
      proper context, and then counsel patients objectively about available management
      strategies. With this approach, all patients who might appropriately benefit from
      coronary artery revascularization will be correctly identified, and patients who
      are truly at very low risk (minimal residual coronary artery disease and
      preserved left ventricular function particularly if associated with a patent
      infarct-related artery) may be similarly identified and managed appropriately
      with elimination of unnecessary additional testing and pharmacologic therapy.
      Finally, whatever approach to risk stratification one chooses for an individual
      patient, the importance of and the need to correct and/or ameliorate risk factors
      for coronary artery disease must be recognized and undertaken.

PMID- 1990781
TI  - Role of new antiplatelet agents as adjunctive therapies in thrombolysis.
AB  - Coronary thrombolysis is the treatment of choice for patients with acute Q-wave
      myocardial infarcts who have no contraindications to such therapy. However, the
      time required for thrombolysis and the possibility of reocclusion of the infarct
      related artery remain problematic. Herein are described experimental animal
      studies and clinical evaluations in which attempts have been made to develop
      adjunctive therapies that, when coupled with available thrombolytic
      interventions, might shorten the time to thrombolysis and delay or prevent
      reocclusion. From the studies conducted to date, it is clear that a combined
      thromboxane synthesis inhibitor and receptor antagonist with a serotonin receptor
      antagonist and heparin shorten the time to thrombolysis and delay or prevent
      coronary artery reocclusion in experimental canine models with copper coil
      induced coronary artery thrombi. A monoclonal antibody to the platelet
      glycoprotein IIb/IIIa receptor coupled with tissue plasminogen activator (t-PA)
      and heparin also shortens the time to thrombolysis and delays or prevents
      reocclusion in experimental canine models. Thrombin inhibitors, including heparin
      and synthetic inhibitors, given with t-PA and aspirin, appear to shorten the time
      to thrombolysis and delay or prevent coronary artery reocclusion in experimental
      canine models. Aspirin coupled with intravenous streptokinase reduces mortality
      in patients with presumed acute myocardial infarction, and a combination of
      heparin and t-PA results in infarct-artery patency more frequently than t-PA
      without heparin. Data from these studies are encouraging with regard to the
      possibility of developing effective and relatively safe thrombolytic regimens
      that shorten the time to thrombolysis and delay or prevent coronary artery
      reocclusion.

PMID- 1990782
TI  - Role of new anticoagulants as adjunctive therapy during thrombolysis.
AB  - Procoagulant activity may persist during coronary thrombolysis and result in
      either delay in the time to recanalization or recurrent thrombosis. Although
      heparin and aspirin form the mainstay of current therapy, recurrent thrombosis
      occurs despite adjunctive heparin therapy during thrombolysis. Newer agents that
      inhibit thrombin by antithrombin III-independent mechanisms, or that inhibit
      earlier steps in the coagulation cascade, have been shown to be effective in the
      experimental preparation of coronary thrombolysis. Because heparin-antithrombin
      III is a relatively inefficient inhibitor of thrombin bound to fibrin, agents
      such as hirudin or small peptide inhibitors of the thrombin-active site appear to
      be more effective inhibitors of clot-associated thrombin activity. Inhibition of
      early steps in the coagulation cascade with the inhibitor of tissue factor-factor
      VIIa complex, or with activated protein C, also appears to be an effective
      anticoagulant strategy. In experimental preparations all of these agents have
      shown superiority in preventing recurrent thrombosis compared with heparin, and
      in some cases they appear to accelerate the rate of clot lysis.

PMID- 1990783
TI  - Heparin as an adjunctive treatment after thrombolytic therapy for acute
      myocardial infarction.
AB  - The rationale for considering heparin therapy as an adjunct to thrombolytic
      treatment for patients with acute myocardial infarction is to prevent
      rethrombosis after successful thrombolysis. The risk of reocclusion is high
      immediately after thrombolysis because blood flowing through the newly opened
      coronary artery is exposed to thrombin bound to fibrin in the residual thrombus.
      Clinical studies of patients with venous thrombosis and acute myocardial
      infarction indicate that there is a relation between the anticoagulant response
      to heparin and clinical efficacy and that the concept of a therapeutic heparin
      level is valid. Subcutaneous doses of approximately 15,000 U twice a day fail to
      provide an adequate anticoagulant response at 24 hours in the majority of
      patients, whereas intravenous administration of a bolus of 5,000 U followed by
      continuous infusion of 30,000 U per 24 hours produces an adequate anticoagulant
      response at 24 hours in approximately 80% of patients. Studies of patients with
      myocardial infarction who received streptokinase showed a significant beneficial
      effect on mortality when 12,500 U of heparin was administered subcutaneously 2
      times per day. In contrast, the single largest study evaluating heparin 12,500 U
      administered subcutaneously 2 times per day as an adjunct to recombinant tissue
      type plasminogen activator (rt-PA) treatment did not show a beneficial effect on
      mortality. However, studies using full-dose intravenous heparin therapy
      demonstrated that heparin improves patency after coronary thrombolysis with rt
      PA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1990784
TI  - Prognostic importance of delayed Q-wave evolution 3 to 24 hours after initiation
      of thrombolytic therapy for acute myocardial infarction.
AB  - The timing of Q-wave evolution and its prognostic significance was studied in 201
      patients who received thrombolytic therapy for a first acute myocardial
      infarction (AMI). One hundred forty-one patients (70%) had evidence of a Q-wave
      AMI within 3 hours of the initiation of thrombolytic therapy, 31 (16%) developed
      Q waves after 3 hours but before hospital discharge, and 29 (14%) were discharged
      with a non-Q-wave AMI. Laboratory indicators of myocardial damage and in-hospital
      morbidity and mortality were greater among patients with Q-wave AMIs than with
      non-Q-wave AMIs. When these indexes were examined with respect to the timing of Q
      wave evolution, the prognosis of patients with delayed Q-wave development was
      similar to that of patients with non-Q-wave AMIs. Thus, compared to patients with
      early (less than or equal to 3 hours) Q-wave evolution, patients with delayed Q
      wave evolution or with a non-Q-wave AMI had a smaller creatine kinase peak (mean
      661 to 1,081 vs 1,251 to 1,541 IU; p = 0.005), better preservation of left
      ventricular function as measured by radionuclide ventriculography before
      discharge (mean +/- standard deviation 54 +/- 11% vs 47 +/- 13%; p less than
      0.01), and a lower incidence of congestive heart failure at discharge (3 vs 15%;
      p = 0.02). In-hospital mortality was lower among patients with delayed Q-wave
      evolution or with a non-Q-wave AMI (5 of 141 vs 0 of 60; difference not
      significant).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1990785
TI  - Regional cardiac adrenergic function using I-123 meta-iodobenzylguanidine
      tomographic imaging after acute myocardial infarction.
AB  - The effect of acute myocardial infarction (AMI) on regional cardiac adrenergic
      function was studied in 27 patients mean +/- standard deviation 10 +/- 4 days
      after AMI. Regional adrenergic function was evaluated noninvasively with I-123
      meta-iodobenzylguanidine (MIBG) using a dedicated 3-detector tomograph. Four
      hours after its administration, there was reduced MIBG uptake in the region of
      infarction, 0.38 +/- 0.31 counts/pixel/mCi x 103 compared with 0.60 +/- 0.30
      counts/pixel/mCi x 103 and 0.92 +/- 0.35 counts/pixel/mCi x 103 in the zones
      bordering and distant from the infarct area, respectively, p less than 0.001. In
      all patients, the area of reduced MIBG uptake after 4 hours was more extensive
      that the associated thallium-201 perfusion defect with defect scores of 52 +/- 22
      and 23 +/- 18%, respectively, p less than 0.001. After anterior wall AMI, the 4
      hour MIBG defect score was 70 +/- 13% and the degree of mismatch between
      myocardial perfusion and MIBG uptake was 30 +/- 9% compared with 39 +/- 17 and 21
      +/- 17% after inferior AMI, p less than 0.001 and p = 0.016, respectively. The 4
      hour MIBG defect score correlated inversely with the predischarge left
      ventricular ejection fraction, r = -0.73, p less than 0.001. Patients with
      ventricular arrhythmia of greater than or equal to 1 ventricular premature
      complexes per hour, paired ventricular premature complexes or ventricular
      tachycardia detected during the late hospital phase had higher 4-hour MIBG defect
      scores, 62.5 +/- 15.0%, than patients with no detectable complex ventricular
      ectopic activity and a ventricular premature complex frequency of less than 1 per
      hour, 44.6 +/- 23.4%, p = 0.036.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1990786
TI  - Insensitivity of noninvasive tests to detect coronary artery vasculopathy after
      heart transplant.
AB  - Obstructive coronary artery vasculopathy can be a major problem after cardiac
      transplant. The use of noninvasive tests to detect coronary artery vasculopathy
      was studied in 73 consecutive patients after heart transplant. Angiographically
      or autopsy-proved coronary artery disease was noted in 19 consecutive patients
      (26%) followed prospectively for 2.5 +/- 1.3 years (mean +/- standard deviation).
      Patients underwent yearly surveillance echocardiographic, rest/exercise-gated
      wall motion, oral dipyridamole thallium, ambulatory electrocardiographic monitor
      and angiographic studies. Positive test results were defined by decrease in
      ejection fraction, wall motion abnormality, failure to increase ejection
      fraction, lack of systolic blood pressure increase, and ischemic ST changes at
      maximal exercise (or on ambulatory monitor). Wall motion abnormalities and
      depressed ejection fraction on echocardiography were also abnormal studies as
      were fixed or reversible perfusion defects on thallium scan. Angiograms were
      considered positive when 50% luminal narrowing was observed and autopsy coronary
      artery vasculopathy was defined as cross-sectional coronary obstruction greater
      than or equal to 70%. No procedure that was examined proved to be a sensitive
      noninvasive detector of heart transplant coronary artery vasculopathy. All except
      ambulatory electrocardiographic monitoring had positive predictive values less
      than 50%. Interestingly, of the techniques evaluated, echocardiography was most
      sensitive (53%). The poor predictive ability of noninvasive testing in this
      population may be due to the fact that these tests are designed to detect effects
      of ischemia rather than coronary obstruction alone. Use of these particular
      noninvasive modalities routinely after heart transplant to detect coronary artery
      vasculopathy should be reconsidered because of their low sensitivity and
      predictive value when used as a surveillance screen.

PMID- 1990787
TI  - Comparative effects of overweight on cardiovascular risk in younger versus older
      men.
AB  - The relation of age and body mass index (BMI) to atherosclerosis risk factors was
      examined in 357 men. Older (greater than or equal to 45 years) men had higher (p
      less than 0.01) systolic and diastolic blood pressures, fasting cholesterol and
      glucose, and 1-hour glucose and insulin levels. Fasting insulin and triglyceride
      levels were not significantly different between the 2 age groups. Although older
      men (n = 170) had greater values for several risk factors, overweight (BMI
      greater than 25.5 kg/m2) increased risk factors more in men younger than 45 years
      (n = 187). In younger men, those with higher BMIs had a greater prevalence,
      respectively, of blood pressure greater than 140/90 mm Hg (35.2 vs 11.2%, p less
      than 0.0001), cholesterol greater than 200 mg/dl (53.5 vs 29.3%, p less than
      0.001), fasting triglycerides greater than 150 mg/dl (38.0 vs 10.3%, p less than
      0.0001), 1-hour glucose greater than 160 mg/dl (15.5 vs 5.2%, p less than 0.05),
      fasting insulin greater than 11 microU/ml (28.2 vs 5.2%, p less than 0.0001), and
      1-hour insulin greater than 110 microU/ml (28.2 vs 9.5%, p less than 0.001). In
      contrast, among older men, the prevalence of elevated blood pressure,
      cholesterol, triglycerides and glucose values was not significantly greater in
      the subgroup with high BMI. However, elevations of fasting (19.6 vs 6.4%, p less
      than 0.05) and 1-hour insulin (29.3 vs 11.5%, p less than 0.01) values were more
      common among older men with higher BMIs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1990788
TI  - Immediate and short-term results of a 1988-1989 coronary angioplasty registry.
AB  - To determine the relevance of recent refinements in angioplasty technology to our
      particular practice, the records of 507 consecutive patients undergoing a first
      percutaneous transluminal coronary angioplasty (PTCA) at our center between
      October 1988 and May 1989 were reviewed. At the time of PTCA, 41% of these
      patients had class IV angina and 44% were identified as having multivessel
      disease. Dilatation was attempted in 734 lesions (mean 1.5 per patient), of which
      95 (13%) were chronic total occlusions. Overall, 69% of the 734 lesions were
      judged anatomically complex, and, in dilating these lesions, a rail-type device
      was used almost exclusively. Successful dilatation was achieved in 659 of the 734
      (90%) attempted lesions. There were low incidences of the major complications of
      death (0.4%), myocardial infarction (1.8%) and emergency bypass surgery (1.8%).
      Acute rethrombosis occurred in 54 patients (11%). In these patients, initial
      strategy of repeat dilatation was successful in 38 of 47 patients (81%). Overall,
      primary clinical success at PTCA was achieved in 480 patients (95%). At a mean
      follow-up of 7.5 +/- 1.5 months in 497 of the study patients, the event-free rate
      (freedom from cardiac death, myocardial infarction, repeat PTCA or coronary
      bypass surgery or recurrence of severe [class III to IV] angina) was 71%. In
      conclusion, despite the often complex coronary disease in patients currently
      presenting to our center, a high initial success rate and acceptable short-term
      outcome of PTCA was achieved.

PMID- 1990789
TI  - Sustained reduction in valvular regurgitation and atrial volumes with tailored
      vasodilator therapy in advanced congestive heart failure secondary to dilated
      (ischemic or idiopathic) cardiomyopathy.
AB  - Afterload reduction therapy can acutely improve hemodynamic function in patients
      with advanced heart failure; however, it is unknown if initial reductions in
      mitral and tricuspid regurgitation and atrial volumes can be sustained with oral
      therapy. Atrial volumes and atrioventricular valve regurgitation were measured
      using 2-dimensional and Doppler echocardiography with color-flow imaging in 14
      patients with dilated heart failure (ejection fraction 17 +/- 4%) before and
      after 3 +/- 1 days of intensive vasodilator and diuretic therapy tailored to
      hemodynamic goals. Echocardiography was repeated again after 6 +/- 2 months on
      oral vasodilators and a flexible diuretic regimen. Acute therapy reduced systemic
      vascular resistance from 1,760 +/- 460 to 1,010 +/- 310 dynes.s.cm-5, pulmonary
      artery wedge pressure from 30 +/- 5 to 17 +/- 4 mm Hg, and right atrial pressure
      from 13 +/- 5 to 7 +/- 3 mm Hg, and led to a 61% increase in stroke volume (from
      36 +/- 10 to 58 +/- 14 ml) (p less than 0.01). Mitral and tricuspid
      regurgitation, determined by color-flow fraction, initially decreased from 0.34
      +/- 0.17 to 0.20 +/- 0.20 and from 0.33 +/- 0.15 to 0.13 +/- 0.13, respectively
      (p less than 0.001). This reduction was sustained at 6 months. Significant
      decreases occurred with acute therapy, with further reductions at 6 months in
      both mean left atrial volume (from 100 +/- 25 to 80 +/- 19 to 65 +/- 15 cm3) and
      right atrial volume (from 85 +/- 23 to 64 +/- 23 to 52 +/- 14 cm3) (p less than
      0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1990790
TI  - Frequency and severity of mitral regurgitation one year after balloon mitral
      valvuloplasty.
AB  - Mitral regurgitation (MR) was evaluated by Doppler echocardiography in 59
      patients with mitral stenosis before, immediately after and 1 year after balloon
      mitral valvuloplasty (BMV). The severity of MR was graded on a scale from 1+ to
      4+. Echocardiographic and hemodynamic variables were analyzed to study the
      potential factor(s) that might predict the long-term persistence of MR.
      Echocardiographic variables were mitral valve thickness and motion, subvalvular
      change, left atrial dimension, commissural calcification and effective
      balloon/mitral anular diameters. Hemodynamic variables were mitral pressure
      gradient, pulmonary arterial pressure, ejection fraction, mitral valve area
      index, age, gender and cardiac rhythm. Mitral valve area index increased from 0.9
      +/- 0.5 to 1.5 +/- 0.8 cm2/m2 immediately after BMW, and to 1.4 +/- 0.3 cm2/m2 at
      1 year follow-up (p less than 0.01). Immediately after BMV, MR grading did not
      change in 30 patients (51%), increased by 1+ in 23 patients (39%), by 2+ in 2
      patients (3.3%) and by 3+ in 2 patients (3.3%), and decreased by 1+ in 2 others.
      At 1-year follow-up, only 1 patient with severe MR required valve replacement.
      Fifty-one patients (88%) had no change in the extent of MR (less than or equal to
      1+) and 6 patients (10%) had a 1-grade decrease in their MR; only 1 patient had a
      1-grade increase in MR. No clinical or hemodynamic variables or morphologic
      characteristics of the mitral valve could predict the development of significant
      MR after BMV. It is concluded that an increment in MR severity less than or equal
      to 2+ is frequently seen after BMV.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1990791
TI  - Reference values and reproducibility of Doppler echocardiography in the
      assessment of the tricuspid valve and right ventricular diastolic function in
      normal subjects.
AB  - The Doppler echocardiographic indexes of the tricuspid and mitral valves were
      assessed in 74 normal subjects (35 women and 39 men, mean age 45 years). A
      reproducibility study was also performed to examine the various sources of
      technical and biological variability. There were significantly higher peak early
      and late flow velocities across the mitral valve than across the tricuspid valve
      (0.67 +/- 0.13 and 0.47 +/- 0.12 vs 0.51 +/- 0.08 and 0.35 +/- 0.09 m.s-1,
      respectively; all p less than 0.0001). There was no significant difference
      between the early:late (E:A) velocity ratios of the 2 valves (1.65 +/- 0.73 vs
      1.75 +/- 0.67, p less than 0.01). There was a steeper mitral early deceleration
      slope (-3.59 +/- 1.07 vs -2.95 +/- 0.91 m.s-2) but no significant difference in
      pressure half-times across the 2 valves (47 +/- 7 vs 51 +/- 12 ms, p less than
      0.1). No influence of gender or body surface area could be demonstrated. There
      was a weak but significant relation between mitral peak early, peak atrial
      velocity and E:A ratio and age (r = -0.39, p less than 0.001, r = 0.23, p less
      than 0.01, and r = -0.245, p less than 0.01, respectively). There was no
      significant correlation between any of the tricuspid flow parameters and age.
      Respiration caused pronounced variability in the tricuspid Doppler indexes and
      all tricuspid flows were sampled and analyzed only during inspiration. The intra-
      and interobserver variabilities were small for all of the Doppler indexes
      measured, but the day-to-day variability was quite significant especially for the
      pressure half-time, deceleration and acceleration slope values.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1990792
TI  - Hemodynamic and electrophysiologic evaluation of patients with hypertrophic
      cardiomyopathy surviving cardiac arrest.
AB  - Hemodynamic and electrophysiologic studies were performed in 30 survivors of
      sudden cardiac arrest with hypertrophic cardiomyopathy (HC) to determine
      responsible factors. Electrophysiologic abnormalities alone were present in 27
      patients (90%): sinus node dysfunction in 14 (47%), delayed atrio-ventricular
      nodal conduction in 1 (3%), abnormal His-Purkinje conduction in 7 (23%), an
      inducible atrial tachycardia in 7 (23%), and inducible sustained ventricular
      arrhythmia in 21 (70%). Sustained ventricular arrhythmia was polymorphic
      ventricular tachycardia (VT) in 18 patients (86%), monomorphic VT in 2 patients
      (7%) and ventricular fibrillation in 1 patient (3%). In 1 patient the arrhythmia
      recorded during an episode of cardiac arrest and induced at electrophysiologic
      study was polymorphic VT. VT was induced with less than or equal to 2 extra
      stimuli in only 1 patient (3%) but with less than or equal to 3 extra-stimuli in
      20 patients (97%). Potential causes of sudden cardiac arrest were found in all
      patients and were multiple in 13 patients (43%). These were (1) ventricular
      electrical instability in 21 patients (70%), (2) severe left ventricular outflow
      tract obstruction in 8 patients (27%), (3) bradycardia in 5 patients (17%), (4)
      myocardial ischemia associated with hypotension in 5 patients (17%), and (5)
      atrial tachycardia resulting in hypotension in 4 patients (13%). Of the 21
      patients with inducible sustained ventricular arrhythmia, 17 received an
      implantable defibrillator device and 4 were treated with antiarrhythmic drugs.
      Seven patients underwent left ventricular septal myectomy.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1990793
TI  - Uses and limitations of transthoracic echocardiography in the assessment of
      atrial septal defect in the adult.
AB  - Two-dimensional and color Doppler echocardiography accurately detected the
      presence of an atrial septal defect (ASD) in 47 of 50 adults (mean age 40 years)
      confirmed by surgery or cardiac catheterization, or both. It correctly
      categorized all patients with ostium secundum and ostium primum ASD but
      misdiagnosed 3 of 5 patients with surgically proven sinus venosus ASD. The shunt
      flow volume across the ASD was calculated with the standard Doppler equation, and
      assuming the ASD to be circular correlated with shunt flow volume obtained by
      cardiac catheterization (r = 0.74). The maximum width of the color flow signals
      moving across the ASD was taken as its diameter. Mean flow velocity was
      determined either by placing a pulsed Doppler sample volume parallel to the flow
      across the ASD as visualized by color Doppler or by color M-mode examination,
      which allowed determination of flow velocities using a previously validated
      method that incorporates a computer analysis of pixel color intensity. The
      pulmonary to systemic blood flow ratio obtained by color-guided conventional
      Doppler interrogation of the left and right ventricular outflow tracts correlated
      poorly with cardiac catheterization results (r = 0.38). In patients with
      associated tricuspid regurgitation, the peak systolic pulmonary artery pressure
      obtained by color Doppler-guided continuous-wave Doppler correlated well with
      that obtained at cardiac catheterization (r = 0.89). The maximum color Doppler
      jet width of the flow across the ASD poorly correlated with ASD size estimated at
      surgery (r = 0.50).

PMID- 1990795
TI  - Doppler echocardiographic findings in normal-functioning St. Jude Medical and
      Bjork-Shiley mechanical prostheses in the tricuspid valve position.

PMID- 1990794
TI  - Evaluation of the pharmacokinetics and electrocardiographic effects of
      intravenous verapamil with intravenous calcium chloride pretreatment in normal
      subjects.
AB  - To evaluate the effects of calcium pretreatment on the disposition and
      electrocardiographic effects of verapamil, 8 healthy male volunteers received
      treatment in each of 3 phases in a randomized, double-blind, crossover manner.
      Phase I denoted 10 ml of 0.9% intravenous sodium chloride followed by 10 mg of
      intravenous verapamil; phase II denoted 10 ml of 10% intravenous calcium chloride
      followed by 4 ml of 0.9% intravenous sodium chloride; and phase III denoted 10 ml
      of 10% intravenous calcium chloride followed by 10 mg of intravenous verapamil.
      Blood samples for the determination of verapamil concentrations were drawn at 5,
      10, 15, 20, 30, 45, 60 and 90 minutes, and at 2, 4, 6, 10 and 24 hours. Blood
      pressure, heart rate and PR intervals were also measured at these times.
      Pretreatment of verapamil with intravenous calcium did not alter the disposition
      of intravenous verapamil. Blood pressure was not significantly altered in any
      treatment phase, although calcium tended to increase mean arterial pressure and
      verapamil abolished this effect. Calcium had no significant affect on verapamil
      induced PR prolongation (maximum percent change in PR interval: phase I = 19 +/-
      11%, phase III = 18 +/- 7%; time to maximal prolongation: phase I = 0.38 +/- 0.21
      hours, phase III = 0.37 +/- 0.26 hours; and area under the percent change in PR
      vs time curve: phase I = 15.5 +/- 10, phase III = 21 +/- 9). Verapamil caused a
      reflex increase in heart rate of similar magnitude in both phases I and III (24
      +/- 10% and 21 +/- 7%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1990796
TI  - Correlation of the physiologic parameters of a continuous ramp versus an
      incremental James exercise protocol in normal children.

PMID- 1990797
TI  - Risk of dysphagia after transesophageal echocardiography.

PMID- 1990798
TI  - Importance of technical variables for quantitative measurements by color Doppler
      imaging.

PMID- 1990799
TI  - Mercury in the heart.

PMID- 1990800
TI  - Reversible "cardiomyopathy" after accidental adrenaline overdose.

PMID- 1990801
TI  - Persistent left fifth aortic arch with complex coarctation.

PMID- 1990802
TI  - Tricuspid valve honk due to pulmonary hypertension secondary to left atrial
      myxoma.

PMID- 1990803
TI  - Ejection fraction and induced sustained ventricular tachycardia.

PMID- 1990804
TI  - Endomyocardial biopsy in cardiac transplant recipients using the femoral venous
      approach.

PMID- 1990805
TI  - Vasomotor properties of internal mammary arteries, saphenous vein bypass grafts
      and native coronary arteries.

PMID- 1990806
TI  - Comparison of proximal left anterior descending and circumflex coronary artery
      dimensions in aortic valve stenosis and hypertrophic cardiomyopathy.

PMID- 1990807
TI  - Intravenous amiodarone for conversion of atrial fibrillation to sinus rhythm.

PMID- 1990808
TI  - Can the dipyridamole-Doppler stress test detect myocardial ischemia?

PMID- 1990809
TI  - Cardiac transplantation and cancer.

PMID- 1990810
TI  - Atrial septal aneurysm as a "newly discovered" cause of stroke in patients with
      mitral valve prolapse.

PMID- 1990811
TI  - Interaction between amiodarone and phenytoin.

PMID- 1990812
TI  - The sleep electrocardiogram at extreme altitudes.

PMID- 1990813
TI  - Right ventricular diastolic function in children.

PMID- 1990814
TI  - Sudden death associated with exercise: the risk-benefit issue.

PMID- 1990815
TI  - Treatment algorithms for patients with ventricular arrhythmias.

PMID- 1990816
TI  - Antiarrhythmic drugs and cardiac death end points.

PMID- 1990817
TI  - Preoperative imaging of the internal thoracic artery.

PMID- 1990818
TI  - Therapeutic equivalency of procainamide--a correction.

PMID- 1990819
TI  - Class I open bite: a case report.

PMID- 1990820
TI  - Parental data used to predict growth of craniofacial form.
AB  - The sample for this study consisted of 250 families. From 850 lateral and
      posteroanterior cephalograms, 81 variables from the X, Y coordinates of 67
      landmarks were calculated and matched with the normal distribution. Principal
      component analysis was used to summarize these 81 variables in proper factor
      scores. The craniofacial patterns of 500 adults were classified by cluster
      analysis on the basis of those factor scores. This study introduced the concept
      of "similar parent" and "dissimilar parent" instead of the father and mother
      equally. Finally, the following model for predicting the individual growth of
      craniofacial characters was obtained. The predicted value Y(t) [formula: see
      text] is the logistic curve used in growth studies, C1X(s) is for the similar
      parent of a child, and C2X(d) is for the dissimilar parent. Multiple regression
      functions were calculated for both sexes in each of four craniofacial patterns.
      The errors of prediction at the average age of 18 years from the data at the
      average age of 11.6 years were 1.12, 2.88, 2.87, 3.14, and 1.93 mm for the
      respective distances S-N, N-Me, S-Me, Gn-Cd, and G-G'. These errors in our growth
      prediction are much smaller than in ordinary normal facial diagrams and may be
      considered negligible for orthodontic clinical application.

PMID- 1990821
TI  - A comparison of ANB, WITS, AF-BF, and APDI measurements.
AB  - In the present study, the relationships among ANB, Wits, AF-BF, and APDI
      measurements used in the assessment of the anteroposterior jaw disorders were
      examined on the cephalometric radiographs of 63 male and 82 female subjects, and
      high correlations were found among them. Furthermore, relationships were explored
      between these parameters and some measurements that were thought to have
      influenced them. The results of the geometric studies could not be proved on the
      basis of statistical evaluation.

PMID- 1990822
TI  - Growth of the pharynx and its physiologic implications.
AB  - The bony nasopharynx increases its capacity predominantly by means of vertical
      development. Analogous to the facial structures is an expression of some
      somatotopic features that give rise to a higher and more shallow pharyngeal
      dimension in the dolichocephalic growth pattern. The nasopharynx's ultimate
      patency, however, depends on the growth and relative size of the soft tissues
      that line the skeletal boundaries. A decreased patency of the oropharyngeal
      airway can induce some postural adaptations, which secure a constant sagittal
      dimension at that level. However, at a certain critical point, purely nasal
      respiration will be turned into an oronasal breathing pattern, which in turn will
      elicit more compensatory mechanisms. This muscle recruitment is a possible cause
      of a deviant vertical craniofacial growth pattern.

PMID- 1990823
TI  - The dimensions of the tongue in relation to its motility.
AB  - To obtain basic information about the motility and dimensions of the tongue, the
      tongue volume was measured and the change in its length and location was noted
      while the tongue was undergoing protrusion, and then the relationships among
      those parameters were examined statistically. The tongue was measured at rest
      from the tip to a point 40 mm posterior corresponding to a plane connecting the
      lower permanent second molars. The subjects were 100 Japanese men and women. It
      was found that (1) maximum protrusion of the tongue is accomplished by two
      functions combined--a forward movement and a longitudinal stretching; the volume
      of the tongue was significantly correlated with its stretching. (2) The mean
      length of the tongue in the most protruded position was about 20% longer than its
      length in the resting position; it was stretched most in the segment from 1 to 2
      cm posterior to its tip. (3) The mean tongue volume was 25.3 cm3 in men and 22.6
      cm3 in women, a statistically significant sex difference; the volume was about
      12% larger in men than in women. (4) There was no correlation between the tongue
      volume and the length of the most extraorally protruded tongue. The results
      suggested that the volume of the tongue can be estimated from the stretched
      length of the tongue in the most protruded position, if it is measured properly.

PMID- 1990824
TI  - Relationship between vertical dentofacial morphology and respiration in
      adolescents.
AB  - The relationship between vertical dentofacial morphology and respiration has been
      debated and investigated from various approaches. The purpose of this study was
      to use contemporary respirometric techniques to compare the breathing behavior of
      normal and long-faced adolescents. Sixteen normal and 32 long-faced subjects 11
      to 17 years of age were chosen clinically and verified by means of a discriminant
      function. Vertical and anteroposterior facial form was assessed from lateral
      cephalometric radiographs according to the following measurement criteria: six
      skeletal angular, eight skeletal linear, four dental linear, and three skeletal
      ratios. Breathing behavior was quantified according to tidal volume, minimum
      cross-sectional nasal area, and percent of nasal breathing as assessed by
      pneumotachography, measurement of differential pressures, and inductive
      plethysmography. The data indicated that the normal and long-faced groups were
      significantly different with respect to lower face form, and each group in the
      study was comparable to groups that had been chosen by previous investigators.
      Multiple regression analysis demonstrated that the normal and long-faced groups
      had similar tidal volumes and minimum nasal cross-sectional areas, but the long
      faced subjects had significantly smaller components of nasal respiration. These
      results illustrate that groups without significant differences in airway
      impairment can have significantly different breathing modes that may be
      behaviorally based, rather than airway-dependent.

PMID- 1990825
TI  - The effect of orthodontic treatment on plaque and gingivitis.
AB  - The aim of the present investigation was to evaluate the relationship between the
      receipt of orthodontic treatment and subsequent periodontal health. Data from 417
      children who were classified at baseline as having significant occlusal
      variations and who were present at the follow-up examination 3 years later were
      selected from an original cohort of 1015. One hundred fourteen of these children
      received orthodontic treatment over this time period and provided two groups of
      children for comparison in this study. Plaque indices, bleeding indices, and
      degree of dental irregularity were recorded for each incisor and canine tooth.
      There were significant reductions in the plaque and gingivitis scores on all
      tooth surfaces between the baseline and 3-year examination in the two groups of
      children. The children who had received orthodontic treatment had the greater
      reduction, but this appeared to be more related to behavioral factors than to
      improved tooth alignment.

PMID- 1990826
TI  - An in vivo study on the merits of two glass ionomers for the cementation of
      orthodontic bands.
AB  - The purpose of this study was to investigate the cariostatic effect of two glass
      ionomer cements on in vivo demineralization of partly uncovered enamel beneath
      orthodontic bands. A 4-week clinical trial was conducted on a group of five
      patients with nine pairs of premolars to be extracted for orthodontic purposes.
      Specially designed orthodontic bands were cemented with either Ketac-Cem (K-C) or
      Aqua-Cem (A-C). A local cariogenic milieu was created between the buccal surface
      of the premolars and the inner surface of the bands to secure plaque
      accumulation. The mineral content of the teeth was quantified by
      microradiography. The data were compared with data from a previous study of
      patients in the same age group with bands that had been cemented with a non-F
      cement. After comparison with the non-F group, the lesion depth (ld) was reduced
      by 63% for K-C and by 55% for A-C. This reduction was statistically significant
      at the 2.5% level (t test). The total mineral loss in teeth cemented with glass
      ionomer cements (delta Z) was reduced, in comparison with the loss in teeth
      cemented with non-F cement, by 49% with K-C and by 27% with A-C. The differences
      were statistically significant only for the K-C group (t test, p less than
      0.025). There were no significant differences between the two glass ionomer
      cements with respect to either lesion depth or total mineral loss values (paired
      t test; p greater than 0.05). This investigation shows that fluoride released
      from glass ionomer cements contributes substantially to demineralization
      "reduction." However, these cements do not provide complete caries protection in
      sites where access is difficult.

PMID- 1990827
TI  - Legal aspects of orthodontic practice: risk management concepts. Orthodontic
      treatment and facial appearance.

PMID- 1990828
TI  - Growth patterns.

PMID- 1990829
TI  - Enamel fracture caused by ceramic brackets.

PMID- 1990830
TI  - Putting the genetics back into cytogenetics.

PMID- 1990831
TI  - In situ hybridization to cytogenetic bands of yeast artificial chromosomes
      covering 50% of human Xq24-Xq28 DNA.
AB  - From the collection described by Abidi et al., 102 yeast artificial chromosomes
      (YACs) with human DNA inserts more than 300 kb in length were assigned to
      chromosomal band positions on early metaphase chromosomes by in situ
      hybridization using the biotin-avidin method. All the YACs hybridized within the
      Xq24-Xqter region, supporting the origin of the vast majority of the YACs from
      single human X-chromosomal sites. With assignments precise to +/- 0.5 bands, YACs
      were distributed among cytogenetic bands to roughly equal extents. Thus, there is
      no gross bias in the cloning of DNA from different bands into large YACs. To test
      band assignments further, hybridizations were carried out blind, and band
      positions were then compared with (1) probe localizations in cases in which a
      reported location was present in one of the YACs; (2) cross-hybridization of a
      labeled YAC with others in the collection; and (3) hybridization to a panel of
      DNAs from a series of hybrid cells containing Xq DNA truncated at various
      regions. Of 31 cases in which YACs contained a probe with a previously reported
      location, 28 in situ assignments were in agreement, and 14 other assignments,
      including one of the three discordant with probe localization, were confirmed by
      YAC cross-hybridization studies. Results with a group of nine YACs were further
      confirmed with a panel of somatic cell hybrid DNAs from that region. Five YACs
      hybridized both to Xq25 and to a second site (four in Xq27 and one in Xq28),
      suggestive of some duplication of DNA of the hybrid cell and perhaps in normal X
      chromosomes. The in situ assignments are thus sufficient to place YACs easily and
      systematically within bins of about 7-10 Mb and to detect some possible
      anomalies. Furthermore, on the basis of expectations for random cloning of DNA in
      YACs, the assigned YACs probably cover more than 50% of the total Xq24-Xq28
      region. This provides one way to initiate the assembly of YAC contigs over
      extended chromosomal regions.

PMID- 1990832
TI  - Why are autism and the fragile-X syndrome associated? Conceptual and
      methodological issues.
AB  - Investigations of the association between autism and the fragile-X syndrome have
      yielded conflicting results with some studies indicating a strong correlation and
      others indicating no relation between the disorders. In this paper, we review the
      relevant research on this controversy and discuss the conceptual and
      methodological problems involved in such an inquiry. We conclude that autism and
      fragile X are associated and that this relation will prove fruitful in
      understanding the role of the X chromosome in a variety of behavior disorders and
      in unraveling various theoretical accounts on the etiology of autism.

PMID- 1990833
TI  - A dimorphic 4-bp repeat in the cystic fibrosis gene is in absolute linkage
      disequilibrium with the delta F508 mutation: implications for prenatal diagnosis
      and mutation origin.
AB  - The gene causing cystic fibrosis (CF) has been recently cloned, and the major
      mutation (delta F508) accounting for approximately 70% of CF chromosomes has been
      uncovered. We have identified at the 3' end of intron 6 in the CF gene a 4-bp
      tandem repeat (GATT) that exhibits interesting features. First, PCR screening of
      103 normal individuals revealed that the repeat exists only in two polymorphic
      allelic forms, either as a hexamer or a heptamer. These two alleles are in Hardy
      Weinberg equilibrium and predict a heterozygote frequency of 41% (p[seven
      repeats] = .71; q [six repeats] = .29). Second, the allele with six repeats was
      found linked to delta F508 on all 76 CF chromosomes investigated, demonstrating
      strong linkage disequilibrium and suggesting that delta F508 had originated on
      the gene bearing six repeats. Third, when the repeat alleles are linked to the
      DNA markers XV2c and KM19, extended haplotypes are generated. These new
      haplotypes become informative in situations in which prenatal diagnosis cannot be
      performed solely with XV2c and KM19. Since this repeat marker is located in the
      CF gene and would be very less likely to recombine with the gene, it can serve as
      a valuable DNA marker for haplotype analysis. A possible crossover, however, was
      identified between XV2c and KM19, transferring delta F508 to a different
      haplotype.

PMID- 1990834
TI  - Two frameshift mutations in the cystic fibrosis gene.
AB  - Cystic fibrosis (CF) is a recessive disease caused by mutations in the CF
      transmembrane conductance regulator (CFTR) gene. We have identified in exon 7 two
      frameshift mutations, one caused by a two-nucleotide insertion and the other
      caused by a one-nucleotide deletion; these mutations--CF1154insTC and CF1213delT,
      respectively, are predicted to shift the reading frame of the protein and to
      introduce UAA(ochre) termination codons at residues 369 and 368.

PMID- 1990835
TI  - Genetic analysis of breast cancer in the cancer and steroid hormone study.
AB  - The familial risk of breast cancer is investigated in a large population-based,
      case-control study conducted by the Centers for Disease Control. The data set is
      based on 4,730 histologically confirmed breast cancer cases aged 20 to 54 years
      and on 4,688 controls who were frequency matched to cases on the basis of both
      geographic region and 5-year categories of age, and it includes family histories,
      obtained through interviews of cases and controls, of breast cancer in mothers
      and sisters. Segregation analysis and goodness-of-fit tests of genetic models
      provide evidence for the existence of a rare autosomal dominant allele (q =
      .0033) leading to increased susceptibility to breast cancer. The effect of
      genotype on the risk of breast cancer is shown to be a function of a woman's age.
      Although, compared with noncarriers, carriers of the allele appear to be at
      greater risk at all ages, the ratio of age-specific risks is greatest at young
      ages and declines steadily thereafter. The proportion of cases predicted to carry
      the allele is highest (36%) among cases aged 20-29 years. This proportion
      gradually decreases to 1% among cases aged 80 years or older. The cumulative
      lifetime risk of breast cancer for women who carry the susceptibility allele is
      predicted to be high, approximately 92%, while the cumulative lifetime risk for
      noncarriers is estimated to be approximately 10%.

PMID- 1990836
TI  - High-resolution linkage mapping for susceptibility genes in human polygenic
      disease: insulin-dependent diabetes mellitus and chromosome 11q.
AB  - Insulin-dependent diabetes mellitus (IDDM) has a complex pattern of genetic
      inheritance. In addition to genes mapping to the major histocompatibility complex
      (MHC), several lines of evidence point to the existence of other genetic
      susceptibility factors. Recent studies of the nonobese diabetic mouse (NOD) model
      of IDDM have suggested the presence, on mouse chromosome 9, of a susceptibility
      gene linked to the locus encoding the T-cell antigen, Thy-1. A region on human
      chromosome 11q is syntenic to this region on mouse chromosome 9. We have used a
      set of polymorphic DNA markers from chromosome 11q to investigate this region for
      linkage to a susceptibility gene in 81 multiplex diabetic pedigrees. The data
      were investigated by maximization of lod scores over genetic models and by
      multiple-locus affected-sib-pair analysis. We were able to exclude the presence
      of a susceptibility gene (location scores less than -2) throughout greater than
      90% of the chromosome 11q homology region, under the assumption that the
      susceptibility factor would cause greater than 50% of affected sib pairs to share
      two alleles identical by descent. Theoretical estimates of the power to map
      susceptibility genes with a high-resolution map of linked markers in a candidate
      region were made, using HLA as a model locus. This result illustrates the
      feasibility that IDDM linkage studies using mapped sets of polymorphic DNA
      markers have, both for other areas of the genome in IDDM and for other polygenic
      diseases. The analytic approaches introduced here will be useful for affected-sib
      pair studies of other complex phenotypes.

PMID- 1990837
TI  - Progress in the search for genetic linkage with Tourette syndrome: an exclusion
      map covering more than 50% of the autosomal genome.
AB  - Gilles de la Tourette syndrome is a neuropsychiatric disorder with an autosomal
      dominant mode of inheritance and reduced penetrance at a single genetic locus.
      Several research groups have genetic linkage studies underway to detect the
      chromosomal location of the gene that predisposes for this disorder. Strong and
      clear evidence of linkage has not yet been produced for Tourette syndrome. This
      paper presents an overview of the methods and progress of the groups centered at
      Yale University and Erasmus University in excluding linkage from a large portion
      of the genome. Our labs have screened 228 genetic marker loci for linkage with a
      gene for this disorder in a series of affected families in the United States,
      Canada, The Netherlands, and Norway. More than 50% (and perhaps as much as 66%)
      of the autosomal genome has now been excluded on the assumption that genetic
      heterogeneity is not an important factor in the Tourette syndrome pedigrees
      pooled for this summary.

PMID- 1990838
TI  - Differentiation of Duchenne and Becker muscular dystrophy phenotypes with amino-
      and carboxy-terminal antisera specific for dystrophin.
AB  - Antibodies directed against the amino- and carboxy-terminal regions of dystrophin
      have been used to characterize 25 Duchenne muscular dystrophy (DMD), two
      intermediate, and two Becker muscular dystrophy (BMD) patients. Western blot
      analysis revealed an altered-size (truncated) immunoreactive dystrophin band in
      11 of the 25 DMD patients, in one of the two intermediate patients, and in both
      BMD patients, when immunostained with antiserum raised against the amino terminus
      of dystrophin. None of the DMD or intermediate patients demonstrated an
      immunoreactive dystrophin band when immunostained with an antiserum specific for
      the carboxy terminus of the protein. In contrast, dystrophin was detected in both
      BMD patients by the antiserum specific for the carboxy terminus. Quantitative
      studies indicated that the relative abundance of dystrophin in patients with a
      severe (DMD), intermediate, or mild (BMD) phenotype may overlap, therefore
      suggesting that differential diagnosis of disease severity based entirely on
      dystrophin quantitation may be unsatisfactory. Our results suggest that a
      differential diagnosis between DMD and BMD would benefit from examination of both
      the N terminus and C terminus of the protein, in addition to measurements of the
      relative abundance of the protein.

PMID- 1990839
TI  - A mutation in the pro alpha 2(I) gene (COL1A2) for type I procollagen in Ehlers
      Danlos syndrome type VII: evidence suggesting that skipping of exon 6 in RNA
      splicing may be a common cause of the phenotype.
AB  - Fibroblasts from a proband with Ehlers-Danlos syndrome type VII synthesized
      approximately equal amounts of normal and shortened pro alpha 2(I) chains of type
      I procollagen. Nuclease S1 probe protection experiments with mRNA demonstrated
      that the pro alpha 2(I) chains were shortened because of a deletion of most or
      all of the 54 nucleotides in exon 6, the exon that contains codons for the
      cleavage site for procollagen N-proteinase. Sequencing of genomic clones revealed
      a single-base mutation that converted the first nucleotide of intron 6 from G to
      A. Therefore, the mutation was a change, in the -GT-consensus splice site, that
      produced efficient exon skipping. Allele-specific oligonucleotide hybridizations
      demonstrated that the proband's mother, father, and brother did not have the
      mutation. Therefore, the mutation was a sporadic one. Analysis of potential 5'
      splice sites in the 5' end of intron 6 indicated that none had favorable values
      by the two commonly employed techniques for evaluating such sites. The proband is
      the fourth reported proband with Ehlers-Danlos syndrome VII with a single-base
      mutation that causes skipping of exon 6 in the splicing of RNA from either the
      COL1A1 gene or COL1A2 gene. No other mutations in the two type I procollagen
      genes have been found in the syndrome. Therefore, such mutations may be a common
      cause of the phenotype. The primers developed should be useful in screening for
      the same or similar mutations causing the disease.

PMID- 1990841
TI  - Molecular genetic basis of maple syrup urine disease in a family with two
      defective alleles for branched chain acyltransferase and localization of the gene
      to human chromosome 1.
AB  - Maple syrup urine disease in humans results from inherited defects in branched
      chain alpha-ketoacid dehydrogenase, a mitochondrial multienzyme complex. A
      variety of genetic changes may produce this phenotype by affecting the function
      of any of the three complex-specific subunits. The varied clinical expression
      observed in patients may be partially explained by the defects in the involved
      subunit. Here we report localization of the gene for the branched chain
      acyltransferase component of the complex to human chromosome 1 and describe a
      proband who is a compound heterozygote at this locus. One allele, inherited from
      the father, produces transcripts with 124 nucleotides deleted from the coding
      region. The deletion is not found in the branched chain acyltransferase gene,
      implying that the deleted transcripts arise by an error in transcript processing.
      Cells from the patient's mother contain 50% of the normal amount of mRNA for the
      subunit, and the proband has inherited this nonexpressing allele from her. As a
      result, the proband produces no acyltransferase protein and therefore has greatly
      impaired complex activity. A phenotypically normal sibling is shown to be
      genetically similar to the mother having inherited the mother's nonexpressing
      allele and the father's normal allele.

PMID- 1990840
TI  - Saturating the region of the polycystic kidney disease gene with NotI linking
      clones.
AB  - A NotI-linking library was constructed from a radiation hybrid containing
      fragments of human chromosome 16. The clones were mapped on a panel of somatic
      cell hybrids, and 10 different NotI site-containing clones were localized close
      to and between genetic markers flanking the PKD1 locus. With pulsed-field gel
      analysis the clones were shown to be distributed over four adjacent ClaI
      fragments covering 1,200 kb.

PMID- 1990842
TI  - Identification of a serum protein polymorphism via two-dimensional
      electrophoresis. Family and population studies in two genetically isolated
      groups: North American Hutterites and Australian aborigines.
AB  - We report the identification and initial family and population studies of a
      previously undescribed serum protein polymorphism with two allelic forms. It was
      discovered in Hutterites, a reproductively isolated religious sect, and is also
      present in Australian aborigines and a sample of Chicago residents. A two-allele
      model is consistent with the segregation pattern observed in five kindreds within
      our initial study group. This polymorphism, provisionally designated SPPM-158,
      appears as a horizontal (charge-based) doublet in silver-stained ISO-DALT high
      resolution two-dimensional electrophoresis gels. It is a low-concentration
      polypeptide (approximately 1 mg/dL) that has an apparent MWSDS of 43.6 kD and an
      isoelectric point of approximately 5.5. We infer that it circulates as a multimer
      or in a high-molecular-weight (greater than 200 kD) complex with other proteins
      because it is not observed in normal body fluids derived from physiologically
      ultrafiltered plasma such as amniotic fluid, urine, or cerebrospinal fluid;
      however, it is present in urine of patients with glomerular proteinuria. The high
      heterozygosity rates imply utility of this new serum protein marker for both
      forensic and population studies.

PMID- 1990843
TI  - Population variation of human mtDNA control region sequences detected by
      enzymatic amplification and sequence-specific oligonucleotide probes.
AB  - A method for detecting sequence variation of hypervariable segments of the mtDNA
      control region was developed. The technique uses hybridization of sequence
      specific oligonucleotide (SSO) probes to DNA sequences that have been amplified
      by PCR. The nucleotide sequences of the two hypervariable segments of the mtDNA
      control region from 52 individuals were determined; these sequences were then
      used to define nine regions suitable for SSO typing. A total of 23 SSO probes
      were used to detect sequence variants at these nine regions in 525 individuals
      from five ethnic groups (African, Asian, Caucasian, Japanese, and Mexican). The
      SSO typing revealed an enormous amount of variability, with 274 mtDNA types
      observed among these 525 individuals and with diversity values, for each
      population, exceeding .95. For each of the nine mtDNA regions significant
      differences in the frequencies of sequence variants were observed between these
      five populations. The mtDNA SSO-typing system was successfully applied to a case
      involving individual identification of skeletal remains; the probability of a
      random match was approximately 0.7%. The potential useful applications of this
      mtDNA SSO-typing system thus include the analysis of individual identity as well
      as population genetic studies.

PMID- 1990844
TI  - No severe bottleneck during human evolution: evidence from two apolipoprotein C
      II deficiency alleles.
AB  - The DNA sequences of a Japanese and a Venezuelan apolipoprotein (apo) C-II
      deficiency allele, of a normal Japanese apo C-II gene, and of a chimpanzee apo C
      II gene were amplified by PCR, and their nucleotide sequences were determined on
      multiple clones of the PCR products. The normal Japanese sequence is identical to
      -and the chimpanzee sequence differs by only three nucleotides from--a previously
      published normal Caucasian sequence. In contrast, the two human mutant sequences
      each differ from the normal apo C-II gene sequence by several nucleotides,
      including deletions. The data suggest that both mutant alleles arose greater than
      500,000 years ago. It is shown that a defective allele can persist in a
      population for only a short time if a bottleneck occurs. Therefore, the antiquity
      of the two alleles suggests no severe bottleneck during human evolution.
      Moreover, the fact that one allele is from Japan and the other is from a
      Venezuelan Caucasian family is more consistent with the multiregional evolution
      model of modern human origins than with the complete replacement or "out of
      Africa" model.

PMID- 1990845
TI  - Protection against malaria morbidity: near-fixation of the alpha-thalassemia gene
      in a Nepalese population.
AB  - We have previously reported that the Tharu people of the Terai region in southern
      Nepal have an incidence of malaria about sevenfold lower than that of synpatric
      non-Tharu people. In order to find out whether this marked resistance against
      malaria has a genetic basis, we have now determined in these populations the
      prevalence of candidate protective genes and have performed in-vitro cultures of
      Plasmodium falciparum in both Tharu and non-Tharu red cells. We have found
      significant but relatively low and variable frequencies of beta-thal, beta S,
      G6PD (-), and Duffy (a-b-) in different parts of the Terai region. The average in
      vitro rate of invasion and of parasite multiplication did not differ
      significantly in red cells from Tharus versus those from non-Tharu controls. By
      contrast, the frequency of alpha-thalassemia is uniformly high in Tharus, with
      the majority of them having the homozygous alpha-/alpha-genotype and an overall
      alpha-thal gene (alpha-) frequency of .8. We suggest that holoendemic malaria has
      caused preferential survival of subjects with alpha-thal and that this genetic
      factor has enabled the Tharus as a population to survive for centuries in a
      malaria-holoendemic area. From our data we estimate that the alpha-thal
      homozygous state decreases morbidity from malaria by about 10-fold. This is an
      example of selection evolution toward fixation of an otherwise abnormal gene.

PMID- 1990846
TI  - Genetic population structure of Italy. II. Physical and cultural barriers to gene
      flow.
AB  - Three approaches were employed to evaluate the relative importance of geographic
      and linguistic factors in maintaining genetic differentiation of Italian
      populations as shown by blood groups and erythrocyte and serum markers. Genetic
      distances are closer to linguistic than to geographic distances. Gene-frequency
      change across 12 linguistic boundaries is significantly more rapid than at random
      locations. The zones of sharp genetic variation correspond to physical barriers
      to gene flow and to boundaries between dialect families, which overlap widely.
      However, two linguistically differentiated populations appear genetically
      differentiated despite the absence of physical obstacles to gene flow around
      them. The Po River is associated with abrupt genetic change only in the area
      where it corresponds to a dialect boundary. At most loci the genetic population
      structure seems affected by linguistic rather than geographic factors; exceptions
      are the systems that were subject to malarial selection in geographically close
      but linguistically heterogeneous localities. Gene flow appears to homogenize gene
      frequencies within regions corresponding to dialect families but not between
      them, leading to the patchy distributions of allele frequencies that were
      detected in an earlier study.

PMID- 1990847
TI  - Age at menarche as a fitness trait: further considerations.

PMID- 1990848
TI  - Heterozygotes and homozygotes: discrimination by chemical cleavage of mismatch.

PMID- 1990849
TI  - Uniparental disomy and gene localization.

PMID- 1990850
TI  - Preventing high-risk behavior.

PMID- 1990851
TI  - Case definitions in public health.

PMID- 1990852
TI  - Cardiovascular risk factor levels in ethnic Hawaiians.
AB  - We report a cardiovascular risk factor survey of "native" Hawaiians 20-59 years
      old (70 percent, or 257), living on the Hawaiian Homestead lands on the island of
      Molokai, Hawaii. More than 60 percent of both sexes were overweight. Among males,
      42 percent were smokers. The percent of the population with systolic blood
      pressure greater than 140 mm Hg or a diastolic pressure greater than 90 mm Hg or
      taking hypertensive medications was 14 percent of those ages 20-39 and 36 percent
      of those ages 40-59. The percent with serum cholesterol greater than or equal to
      6.2 mmol/L ranged from 8 percent of those 20-29 years old to 46 percent in those
      50-59 years old. Two percent of those ages 20-29 had a history of diabetes, or 2
      + or greater glycosuria by dipstick, as did 23 percent of those ages 50-59. The
      majority of the known diabetics exhibited glycosuria and elevated glycohemoglobin
      levels, indicating poor control. Hypertension, although usually known to the
      participant, was frequently uncontrolled. From these data, it appears that among
      this group of Hawaiians major risk factors for cardiovascular disease were
      frequent, while at the same time the levels of awareness and/or control for most
      of these factors were low.

PMID- 1990853
TI  - HIV risk behavior reduction following intervention with key opinion leaders of
      population: an experimental analysis.
AB  - BACKGROUND AND PURPOSE: Peer norms influence the adoption of behavior changes to
      reduce risk for HIV (human immunodeficiency virus) infection. By experimentally
      intervening at a community level to modify risk behavior norms, it may be
      possible to promote generalized reductions in HIV risk practices within a
      population. METHODS: We trained persons reliably identified as popular opinion
      leaders among gay men in a small city to serve as behavior change endorsers to
      their peers. The opinion leaders acquired social skills for making these
      endorsements and complied in talking frequently with friends and acquaintances.
      Before and after intervention, we conducted surveys of men patronizing gay clubs
      in the intervention city and in two matched comparison cities. RESULTS: In the
      intervention city, the proportion of men who engaged in any unprotected anal
      intercourse in a two-month period decreased from 36.9 percent to 27.5 percent (
      25 percent from baseline), with a reduction from 27.1 percent to 19.0 percent (
      30 percent from baseline) for unprotected receptive anal intercourse. Relative to
      baseline levels, there was a 16 percent increase in condom use during anal
      intercourse and an 18 percent decrease in the proportion of men with more than
      one sexual partner. Little or no change was observed among men in the comparison
      cities over the same period of time. CONCLUSIONS: Interventions that employ peer
      leaders to endorse change may produce or accelerate population behavior changes
      to lessen risk for HIV infection.

PMID- 1990854
TI  - Motorcycle licensure, ownership, and injury crash involvement.
AB  - The interrelationships among motorcycle licensure, ownership, and injury crash
      involvement were investigated in a sample of 2,723 motorcycle drivers severely or
      fatally injured in California in 1985-86. Owners of motorcycles in such crashes
      ("driver-owners") were less likely to have valid licenses than a random sample of
      motorcycle owners who had not been in crashes (42 vs. 57 percent). Thirty-three
      percent of the crash-involved drivers had valid motorcycle driver's licenses; 39
      percent were operating motorcycles they did not own ("driver-nonowners"). Driver
      nonowners were less likely to be validly licensed than driver-owners (20 percent
      vs. 44 percent). The licensing rate of crash-involved driver-nonowners was 15
      percent if the owner was also unlicensed. Rates of valid licensure were lowest
      among the youngest drivers. Virtually no crash-involved driver-nonowners under
      age 21 were licensed in cases in which the owner was also young and unlicensed.

PMID- 1990855
TI  - Alcohol use and abuse in random samples of physicians and medical students.
AB  - BACKGROUND: This study sought to resolve conflicting views about whether
      physicians are especially prone to alcohol abuse. METHODS: Using an anonymous,
      mailed questionnaire on substance use, we surveyed 500 physicians, 510
      pharmacists, and 974 of their students. The physicians and pharmacists were
      selected randomly from the state society's membership lists, and students
      selected were from local school lists. Follow-up surveys were sent to
      nonresponders at two-week intervals. RESULTS: The physicians and medical students
      did not drink especially heavily and were no more vulnerable to alcoholism than
      were their counterparts in pharmacy and other professions. Physicians differed
      from pharmacists in their style of drinking (greater frequency, smaller
      quantity), but not in total amount of alcohol consumed. Drinking habits among
      physicians were not associated with medical specialty or type of practice, but
      were positively related to gender (males drank more than females) and to age
      (older doctors were more apt to qualify as heavy drinkers than were younger
      doctors). CONCLUSIONS: Physicians were no more likely to abuse substances
      nonmedically than were other professionals. Any group in which alcohol use is
      nearly universal incurs a risk of abuse and impairment that cannot be ignored.

PMID- 1990856
TI  - Validation of a surveillance case definition of carpal tunnel syndrome.
AB  - The National Institute for Occupational Safety and Health (NIOSH) has proposed a
      surveillance case definition for work-related carpal tunnel syndrome (CTS). The
      case definition requires the presence of median nerve symptoms; one or more
      occupational risk factors; and objective evidence of CTS including one of three
      physical examination findings or nerve conduction tests diagnostic of CTS. We
      evaluated the performance of the NIOSH case definition, restricting our analysis
      to cases in which physical examination findings served as the objective
      criterion. Nerve conduction studies were used as the gold standard. Seventy-eight
      workers were studied; 38 percent had CTS. The NIOSH case definition had
      sensitivity of 0.67 (95% CI = 0.57, 0.77), specificity of 0.58 (95% CI = 0.47,
      0.69), and positive and negative predictive values of 0.50 (95% CI = 0.39, 0.61)
      and 0.74 (95% CI = 0.64, 0.84), respectively. Overall 38 percent of subjects were
      classified incorrectly. In a sample with a prevalence of 15 percent, as might be
      encountered in high risk workplaces, the positive predictive value would be 0.22.
      In conclusion, when physical examination findings serve as the objective
      criterion the performance of the case definition is modest reflecting the limited
      diagnostic value of its component tests and indicating that effective screening
      for CTS awaits improved diagnostic techniques.

PMID- 1990858
TI  - Responsible alcohol service: a study of server, manager, and environmental
      impact.
AB  - A responsible alcohol-service training program was evaluated for its impact on
      changing beliefs, knowledge, and behavior in 97 servers and 43 managers and on
      changing establishment policies that encourage safer drinking environments. The
      training program had a significant impact on changing the beliefs and knowledge
      of both servers and managers. Observation 4 to 6 weeks after training showed no
      effects on server behavior, but there was a tendency toward more establishment
      policies compared with controls.

PMID- 1990857
TI  - Behavioral, health and psychosocial factors and risk for HIV infection among
      sexually active homosexual men: the Multicenter AIDS Cohort Study.
AB  - We examined whether 644 homosexual men who engaged in receptive anal intercourse
      were at particularly elevated risk for seroconversion if they also possessed
      specific behavioral, health or psychosocial vulnerability characteristics. Of 11
      potential factors examined, heavy drinking, moderate to heavy drug use, and
      younger age were significantly related to seroconversion. These variables were
      also associated with an increased number of sexual partners, anonymous sex, and
      failure to use condoms.

PMID- 1990859
TI  - Increased risk of ectopic pregnancy with maternal cigarette smoking.
AB  - As part of a case-control study of ectopic pregnancy, we evaluated the potential
      etiologic role of cigarette smoking. Maternal cigarette smoking at the time of
      conception was associated with an increased risk of ectopic pregnancy with a dose
      response relationship (adjusted odds ratios: 1.30 to 2.49). On the other hand,
      partner's smoking was not associated with ectopic pregnancy. The study provides a
      supplementary argument towards a causal effect of smoking in the development of
      ectopic pregnancy.

PMID- 1990860
TI  - Effects of a worksite nonsmoking policy: evidence for increased cessation.
AB  - A random sample of employees was surveyed 20 months after a non-smoking policy
      was implemented at the New England Telephone Company in 1986. Overall, 21 percent
      of respondents who were smoking at the time they heard about the policy had quit
      smoking; 42 percent of quitters said they stopped smoking because of the policy.
      Cessation was highest among those who reported less smoke in their work area, but
      was not related to participation in cessation programs. This study suggests that
      worksite nonsmoking policies may have favorable effects on smoking cessation.

PMID- 1990861
TI  - Are people more health conscious? A longitudinal study of one community.
AB  - Secular changes in cardiovascular health awareness, knowledge and behavior were
      observed in four biennial cross-sectional surveys and a cohort survey in a New
      England community. These changes are not related to more health promotion
      activities in the social milieu of respondents, but are more likely due to
      national mass media health campaigns, the effects of which may influence outcomes
      of community-based cardiovascular disease prevention studies.

PMID- 1990862
TI  - Sexual risk behaviors, AIDS knowledge, and beliefs about AIDS among runaways.
AB  - Sexual risk behaviors, knowledge of acquired immunodeficiency syndrome (AIDS),
      and beliefs about AIDS prevention were examined among 126 runaways. In the
      previous 3 months, 65 percent of youths had been sexually active. Among the
      sexually active runaways, males reported a median of 2.7 partners and females
      reported 1.3 partners, and only 18 percent reported consistent condom use.
      Runaways demonstrated moderately high AIDS knowledge and beliefs endorsing AIDS
      prevention. Condom use and abstinence were directly related to beliefs about
      preventing AIDS.

PMID- 1990863
TI  - Security measures for AIDS and HIV.
AB  - This study describes the measures being taken by AIDS surveillance offices across
      the country to ensure the security of information regarding patients with AIDS
      and HIV infection. Security measures were evaluated according to the cumulative
      number of AIDS cases reported, whether partner notification services were
      provided, and whether HIV seropositive reporting by name was also required. This
      study showed that public health departments have taken extra steps to ensure the
      security of AIDS and HIV data.

PMID- 1990864
TI  - An evaluation of the use of the Statewide Planning and Research Cooperative
      System of New York State as a resource planning tool for HIV infection.
AB  - Hospital discharge records of patients with Pneumocystis carinii pneumonia (PCP)
      in New York State were studied to determine whether cases of human
      immunodeficiency virus (HIV) infection were identified. We estimate that as many
      as 13 percent of hospitalizations of patients with PCP in 1987 and 10 percent of
      those in 1988 were not appropriately identified as HIV related. Identification of
      PCP as HIV related was a function of a hospital's volume of PCP admissions.

PMID- 1990865
TI  - Survival trends of people with AIDS in Washington State.
AB  - Survival rates of 609 cases of acquired immunodeficiency syndrome (AIDS) in
      Washington State diagnosed between 1982 and 1987 according to pre-1987 AIDS
      surveillance definition were analyzed. People with a primary diagnosis of
      Kaposi's sarcoma survived longer than those with Pneumocystis carinii pneumonia.
      Both groups survived longer than those with other diagnoses. Median survival
      increased from 11.3, to 12.5, to 20.8 months for cases diagnosed in or before
      1985, during 1986, and during 1987, respectively.

PMID- 1990866
TI  - Cost of smoking cessation clinics.

PMID- 1990867
TI  - Self-injection and needle sharing among migrant farmworkers.

PMID- 1990868
TI  - Decline in hepatitis B cases.

PMID- 1990869
TI  - A carbon monoxide mass poisoning in an ice arena in Vermont.

PMID- 1990870
TI  - A salute to The American Journal of Surgery on its 100th birthday.

PMID- 1990871
TI  - The future of general surgery.
AB  - The origin of the term "general surgery" is uncertain, but it is known that it
      has been in the lexicon of surgical parlance for more than a century. Although
      specialization began at least 150 years ago, it became a major trend at the end
      of World War I. The potential fragmentation of the specialty is the most
      significant problem currently faced by general surgeons. Other areas affecting
      the future of general surgery are discussed, including residency requirements,
      manpower analyses, and physician reimbursement. Because of rapid technologic
      changes and the aging of the population, surgeons need to incorporate those
      features that will improve patient care into their practices to meet the needs of
      the future.

PMID- 1990872
TI  - Contributions of the Zollinger-Ellison syndrome.
AB  - The salient contributions of the Zollinger-Ellison syndrome have made it unique.
      No pancreatic endocrine tumor described before (insulinoma) or subsequently
      (glucagonoma, somatostatinoma, vipoma, pancreatic-polypeptidoma) has been the
      topic of such a variety of studies, or has been such an inspiration and rich
      source of new ideas for investigation and ultimate improvement in patient care.

PMID- 1990873
TI  - Achievements, present-day problems, and some solutions for trauma care, surgical
      critical care, and surgical education.
AB  - Trauma care represents a serious challenge to general surgery. Forces favoring
      fragmentation of surgery will, if left unchecked, act to the detriment of the
      injured patient. These forces will increase in the future. It is the obligation
      of the surgeon to ensure that further specialization is linked to and does not
      fragment the knowledge base of general surgery. In turn, this obligation needs to
      be acknowledged in surgeons' leadership groups, in every trauma center, and in
      each surgical education program. Acknowledgement preserves the best trauma care
      for injured patients, while at the same time protecting the general surgeon as
      the specialist most suited to provide such care.

PMID- 1990875
TI  - Historical review of pancreaticoduodenectomy.
AB  - The performance of pancreaticoduodenectomy by Whipple in 1935 demonstrated that
      the operation was feasible technically and compatible with reasonable function
      after recovery. From the mid- to late 1940s until the last 10 years, the
      procedure was condemned by many because of its associated mortality and
      morbidity. For reasons that are not clear, the risk of pancreaticoduodenectomy in
      the last 10 years has fallen to less than 10% and in several centers, less than
      5%. Postoperative complications have been reduced and blood transfusions are
      unnecessary in an increasing number of patients. Furthermore, a normal productive
      life without the need for medication and with no digestive disorder is expected.
      Seventy-one percent of patients are able to return to their preoperative
      occupation.

PMID- 1990874
TI  - Transduodenal sphincteroplasty with transampullary septectomy for stenosing
      papillitis.
AB  - The papilla of Vater and its sphincter of Oddi, lying at the confluence of the
      bile and pancreatic ducts in man, have long been suspected as a source of upper
      abdominal pain. Enlarging the opening of the transpapillary segment of the bile
      and major pancreatic ducts by using a transduodenal sphincteroplasty with
      transampullary septectomy resulted in death in a patient with a peripapillary
      diverticulum and pancreas divisum. Eight-six patients followed for 1 to 10 years
      experienced a 75% success rate. Thirty-six patients had a marked stenosis of
      their duct of Wirsung, suggesting that their pain was primarily from the
      pancreas. The remainder had either a generalized narrowing (40 patients) or a
      normal (7 patients) papilla. Pain was not satisfactorily resolved in patients
      with an associated pancreas divisum, chronic pancreatitis, and recurrent episodes
      of acute pancreatitis with alcoholism.

PMID- 1990876
TI  - Trauma systems in Europe.
AB  - For prehospital care, Switzerland developed the first helicopter air rescue
      system but it has been surpassed by the Federal Republic of Germany, where a
      coordinated rescue system of physician-equipped air and terrestrial transport has
      been developed. With regard to hospital care of trauma victims, three systems
      have evolved. In Austria and the Federal Republic of Germany, the "general
      surgeon-traumatologist" is in charge. In these countries, the Workmen's
      Compensation Board restricts treatment privileges to trauma surgeons. In
      Switzerland and Holland, general surgeons in regional hospitals and to some
      extent also in university centers have largely remained responsible for trauma,
      including fractures. In Great Britain, as in other major European countries like
      France, Italy, and Spain, trauma of the locomotor system is the domain of
      orthopedic surgeons, with multiple trauma and body cavities remaining the
      responsibility of general surgeons. Overall, there is a general tendency to
      create integrated trauma care systems within large hospital settings. Although an
      experienced general surgeon can function as the leader of the trauma team, such
      implementation has, for the most part, not occurred.

PMID- 1990877
TI  - Carcinoma of the ductus choledochus.
AB  - A retrospective review of patients treated for carcinoma of the common bile duct
      has demonstrated improvement in diagnostic capabilities, leading to earlier
      management by resectional therapy. The ability to resect these tumors is directly
      translatable to improved long-term survival. Efforts to obtain proof of
      malignancy prior to resection are often frustrated by the inability to obtain
      adequate representative tissue for frozen section. Choledochoscopic biopsies and
      incisional biopsies have given the highest yield of positive diagnoses. In
      experienced hands, a program of fewer preoperative tests with emphasis on early
      operation, diagnosis, and definitive treatment may be more cost-effective in the
      management of patients with common bile duct cancer.

PMID- 1990878
TI  - Adult respiratory distress syndrome.
AB  - Basic scientists and clinicians have written numerous articles on the diverse
      causes of adult respiratory distress syndrome (ARDS). There is no specific
      diagnostic test for ARDS; the condition is characterized by interstitial lung
      edema, reduction in lung compliance, alveolar and small airway closure, decrease
      in functional residual capacity, and persistent hypoxia with increasing amounts
      of pulmonary blood flow coursing through nonventilated or poorly ventilated
      alveoli. Recent studies have emphasized the roles of macrophages and
      polymorphonuclear neutrophils in lung defense and injury. Advances in
      understanding the pathophysiology of ARDS have produced little significant change
      in the clinical management of the syndrome. There is no specific treatment for
      ARDS. The cornerstone of therapy is the early recognition and elimination of
      initiating factors such as sepsis. ARDS is not a single disease process, but
      appears to represent a final common pathway for the manifestation of a variety of
      lung injuries. The goal of therapy is to eliminate the predisposing condition and
      support the patient. New modes of ventilatory and pharmacologic therapy are
      presented.

PMID- 1990879
TI  - The Roux operation for postgastrectomy syndromes.
AB  - The aim of this paper is to describe the technique, indications, and results of
      the Roux operation as used in the treatment of postgastrectomy syndromes. A Roux
      gastrojejunostomy with a 40-cm Roux limb is the procedure of choice for alkaline
      reflux gastritis, because it virtually eliminates reflux of bile and pancreatic
      juice into the stomach. The slow transit through a Roux limb can also be used to
      good advantage to slow gastric emptying in patients with dumping. Patients with
      delayed gastric emptying respond to the combination of near-total gastric
      resection, which removes the atonic gastric remnant and speeds emptying, and Roux
      Y gastrojejunostomy, which prevents reflux esophagitis and provides a reservoir
      for ingesta in the upper gut. After all Roux operations, however, the Roux limb
      may slow emptying so much that pain, fullness, nausea, and food vomiting result,
      the so-called Roux stasis syndrome. Prevention of the Roux stasis syndrome with
      an "uncut" Roux limb and the treatment of the syndrome by using electrical pacing
      to suppress the ectopic pacemakers that emerge in the limb offer possible new
      solutions to this vexing problem.

PMID- 1990880
TI  - Perspectives a century later on the "Ansa en Y" of Cesar Roux.
AB  - During the last 100 years, since Cesar Roux began utilizing his "Ansa-en-Y"
      procedure for gastric outlet obstruction, the procedure at first fell into disuse
      but was later adapted for other applications. This article discusses the
      background of the procedure and compares the original indications with the
      author's current experience. Current applications in this series were for chronic
      pancreatitis (26 patients), alkaline gastritis (22 patients), biliary duct
      obstruction (7 patients), pancreatic pseudocyst (3 patients), and gastric
      substitution (3 patients).

PMID- 1990881
TI  - Cytokines and glucocorticoids in the regulation of the "hepato-skeletal muscle
      axis" in sepsis.
AB  - Sepsis results in muscle catabolism and peripheral release of amino acids with a
      concomitant uptake of amino acids in liver and acute-phase protein synthesis. In
      addition, there appears to be a cytokine-induced process that blocks muscle amino
      acid uptake in sepsis, further diverting amino acids from the periphery to the
      liver. In this article, evidence that cytokines and glucocorticoids play an
      important role in the regulation of hepatic and muscle protein metabolism during
      sepsis is presented.

PMID- 1990883
TI  - Vascular lesions of the intestines.
AB  - This article reviews the pathology, pathophysiology, diagnosis, and treatment of
      vascular lesions of the intestine as a cause of gastrointestinal bleeding. In
      addition, a modified system for classifying such lesions, based on the author's
      personal experience with such lesions, is presented.

PMID- 1990882
TI  - Germfree animals and technics in surgical research.
AB  - Germfree animals have been reared to a size, weight, and age permitting the
      performance of major surgical procedures and the pursuit of a variety of surgical
      research problems. Germfree dogs have been maintained in the isolator system
      through three generations, indicating that life, reproduction, and growth are all
      possible in the absence of microbial contamination. The value of the germfree
      approach to surgical problems has been utilized in studies of a variety of
      gastrointestinal problems, shock, cancer, immunology, burns, wound healing, and
      in direct patient application. Patients have been maintained in isolator
      environments for prevention of infection, for operative procedures, for treatment
      of extensive burns, and for management of immune-suppressed individuals. We
      conclude that germfree animals and germfree technics provide a valuable addition
      to the armamentarium of the surgeon in both research and clinical applications.

PMID- 1990884
TI  - Graduate medical education: issues for the 21st century.

PMID- 1990885
TI  - Bacterial overgrowth and intestinal atrophy in the etiology of gut barrier
      failure in the rat.
AB  - Bacterial translocation occurs in animal models of shock, trauma, sepsis, and
      parenteral or elemental enteral alimentation. Bowel atrophy and cecal bacterial
      overgrowth have both been implicated in the pathophysiology of bacterial
      translocation in many of these models. To further define the etiology of
      bacterial translocation resulting from dietary manipulations, rats were fed a
      elemental/defined-formula diet (DFD) for 2 weeks ad libitum and then randomized
      to either intestinal decontamination with a nonabsorbable antibiotic (neomycin)
      or no antibiotic treatment. Neomycin treatment significantly (p less than 0.01)
      reduced the incidence of bacterial translocation after DFD, in association with a
      significant reduction in the number of cecal gram-negative bacteria. Neither loss
      of bowel mass after DFD nor bowel composition was affected by oral neomycin.
      Bacterial translocation after DFD would thus appear to be the result of cecal
      bacterial overgrowth rather than a loss of a physical intestinal barrier due to
      atrophy.

PMID- 1990886
TI  - Official organs and entangling alliances. The brief association of The American
      Journal of Surgery and the Southern Surgical Association (1932-1935).
AB  - In this article, the short-lived editorial relationship between the Southern
      Surgical Association and The American Journal of Surgery is described. Some of
      the factors that may have been responsible for the abrupt termination of this
      relationship are discussed, including in particular the rejection by the Journal
      editors of certain papers presented before the Association, and the steadfast
      refusal of the Journal to categorize itself as the official publication of any
      organization. Despite the brevity of the relationship, it was of great value to
      the Association, since it served for the first time to bring the scientific
      proceedings of the organization to the attention of the surgical population of
      America and of the English-speaking world.

PMID- 1990887
TI  - An editor's perspective of the future for peer-reviewed traditional surgical
      journals.
AB  - In the opinion of the Journal's Editor, the future of peer-reviewed surgical
      journals is promising. Although problems remain to be solved, including the loss
      of advertising revenues, the reduction of available research funds, and the
      potential for duplication of information, the energy and commitment of editorial
      board members, reviewers, surgical practitioners, and readers will continue to
      have a positive impact and will ensure the survival of the traditional surgical
      journal into the next century.

PMID- 1990888
TI  - Specialization for herniorrhaphy.

PMID- 1990889
TI  - Cholecystectomy: the gold standard.

PMID- 1990890
TI  - Problems faced by the surgeon caring for a patient with gallstone pancreatitis.

PMID- 1990891
TI  - Tube enterostomy after small bowel resection.

PMID- 1990892
TI  - New modes of nerve block.

PMID- 1990893
TI  - Diabetes and surgery.

PMID- 1990894
TI  - Intraoperative detection of patent foramen ovale by transesophageal
      echocardiography.
AB  - This study reports the intraoperative use of contrast and Doppler
      echocardiography techniques to diagnose patent foramen ovale (PFO). Fifty
      patients without known atrial septal defects undergoing elective cardiovascular
      surgery were studied. A 5-MHz esophageal echocardiographic probe was used to
      image the fossa ovalis (FO) and 10 ml agitated saline was injected into the right
      atrium during apnea. Echocardiographic contrast was then injected during end
      inspiration at 20-cmH2O airway pressure. When opacification of the right atrium
      was complete, the airway pressure was released. During these maneuvers, color and
      pulsed-wave Doppler interrogation of the atrial septum were also performed. Right
      to-left passage of saline contrast across the interatrial septum was seen in 11
      of 50 patients (22%). Doppler echocardiography demonstrated a PFO in 2 patients
      without contrast evidence of shunting. Thus, the combination of contrast and
      Doppler echocardiography identified a 26% (13 of 50) prevalence of PFO,
      approximating the previously reported autopsy rate of 25%. These contrast and
      Doppler techniques may be useful in detecting patients at risk for paradoxical
      emboli and in identifying candidates for closure of the PFO.

PMID- 1990895
TI  - Propofol: effective dose and induction characteristics in unpremedicated
      children.
AB  - The induction dose, induction characteristics, and cardiovascular and respiratory
      effects of propofol were studied in 90 unpremedicated children 3-12 yr old.
      Propofol in a dose of 1-3 mg.kg-1 was injected in an antecubital vein over 10-30
      s. Successful induction was defined by loss of eyelash reflex occurring within 50
      s of the conclusion of propofol injection and followed by subsequent acceptance
      of face mask without excessive movement. The effective dose of propofol resulting
      in loss of eyelash reflex in 50% (ED50) and 95% (ED95) of children were 1.3 (1.1
      1.4) and 2.0 (1.7-2.6) mg.kg-1 (95% confidence interval). The corresponding ED50
      and ED95 for a successful induction that included acceptance of face mask were
      1.5 (1.3-1.7) and 2.3 (2.1-3.0), respectively. There was a 6.6% incidence of mild
      to moderate pain on injection and a 12.7% incidence of involuntary movement.
      Apnea (cessation of breathing greater than 20 s) was seen in 21% of patients.
      Blood pressure decreased by more than 20% of baseline value in 48% of patients
      who received halothane (1-3%) after the bolus injection of propofol. It is
      concluded that propofol is an effective induction agent in children. A dose of
      2.5-3.0 mg.kg-1 is recommended to ensure a smooth transition to an inhalational
      maintenance technique. The use of antecubital veins is associated with a low
      incidence of pain on injection.

PMID- 1990896
TI  - Clinical efficacy of oral-transdermal clonidine combinations during the
      perioperative period.
AB  - In an attempt to maintain stable levels of an alpha 2-adrenergic agonist
      throughout the perioperative period, two different oral-transdermal clonidine
      dosage regimens were administered according to a randomized, double-blind,
      placebo-controlled study in patients undergoing abdominal surgery. We determined
      the clinical efficacy of a high- and a low-dose clonidine regimen on sedation,
      hemodynamic parameters, anesthesia, and analgesia. The low-dose clonidine group
      of patients (n = 14) received a 7-cm2 clonidine transdermal patch (Catapres-TTS
      #2), which was supplemented with oral doses of clonidine approximately 3
      micrograms.kg-1 on the evening prior to surgery and on the morning of surgery.
      The high-dose clonidine group (n = 14) received a 10.5-cm2 clonidine transdermal
      patch (Catapres-TTS #3) with oral clonidine approximately 4.5 micrograms.kg-1 at
      bedtime and 6.0 micrograms.kg-1 on the morning of surgery. Placebo-treated
      (control) patients received the same occlusive patch without active ingredient
      and oral placebo tablets at bedtime and on the morning of surgery. Preanesthetic
      medication included midazolam 50 micrograms.kg-1 intramuscularly (im). Anesthesia
      was induced with alfentanil 30 micrograms.kg-1 intravenously (iv), thiopental 3
      mg.kg-1 iv, and vecuronium 0.1 mg.kg-1 iv, and was maintained with 70% nitrous
      oxide in oxygen and a continuous infusion of alfentanil 0.5 microgram.kg-1.min-1.
      Isoflurane was added when the blood pressure exceeded 110% of the patient's
      prestudy value. For pain relief postoperatively, the patients received morphine,
      1-2-mg iv boluses, via a patient-controlled analgesia pump. The low-dose
      clonidine patient group had mean plasma clonidine concentrations that varied from
      1.47 ng.ml-1 (preoperative) to 1.32 ng.ml-1 (postoperative day 2).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1990897
TI  - Isoflurane-induced vasodilation minimally increases cutaneous heat loss.
AB  - Central body temperature, which usually is well controlled, typically decreases
      more than 1 degree C during the 1st h of general anesthesia. This hypothermia has
      been attributed partially to an anesthetic-induced peripheral vasodilation, which
      increases cutaneous heat loss to the environment. Based on the specific heat of
      humans, heat loss would have to increase more than 70 W for 1 h (in a 70-kg
      person) to explain hypothermia after induction of general anesthesia. However,
      during epidural anesthesia, sympathetic blockade increases heat loss only
      slightly. Furthermore, thermoregulatory vasoconstriction in unanesthetized humans
      decreases heat loss to the environment only 15 W. Therefore, we tested the
      hypothesis that the hypothermia that follows induction of general anesthesia does
      not result from increased cutaneous heat loss. Heat loss and skin-surface and
      tympanic membrane temperatures, before and after induction of isoflurane
      anesthesia, were measured in five minimally clothed volunteers. Peripheral skin
      blood flow was evaluated with venous-occlusion volume plethysmography and skin
      surface temperature gradients. Cutaneous heat losses in watts were summed from
      ten area-weighted thermal flux transducers. Tympanic membrane temperature, which
      was stable during the 30-min control period preceding induction, decreased 1.2 +/
      0.2 degrees C in the 50 min after induction. Isoflurane anesthesia decreased
      mean arterial blood pressure approximately 20%. Average skin-surface temperature
      increased over 15 min to 0.5 degree C above control. Heat loss from the trunk,
      head, arms, and legs decreased slightly, whereas loss from the hands and feet
      (10.5% of the body surface area) doubled (P less than 0.01).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1990898
TI  - Plasma concentrations of midazolam in children following intranasal
      administration.
AB  - Nasally administered midazolam appears to be a useful method for rapidly sedating
      children prior to the induction of anesthesia. We determined the peak plasma
      concentrations after intranasal administration of midazolam and compared this to
      plasma concentrations achieved after intravenously administered midazolam in 18
      children between the ages of 14 months and 5 yr, who underwent elective closure
      of an asymptomatic atrial septal or ventricular septal defect. Preanesthetic
      medication was at the discretion of the attending anesthesiologist. Induction of
      anesthesia was with halothane in N2O and O2 via mask, and tracheal intubation was
      performed after the administration of fentanyl or sufentanil plus pancuronium.
      Anesthesia was maintained with these agents, and augmented with halothane or
      isoflurane. As soon as arterial access was established, the patient received 0.1
      mg/kg of either intranasal or intravenous midazolam. Midazolam concentrations
      were measured by gas chromatography-mass spectrometry. Intranasal midazolam
      achieved its peak plasma concentration of 72.2 +/- 27.3 ng/ml in 10.2 +/- 2 min.
      Ten minutes after the administration of midazolam, the mean plasma concentration
      in the intranasal midazolam group was 57% of the concentrations in the group
      receiving midazolam intravenously. These results confirm the clinical impression
      that intranasal administration of midazolam rapidly achieves sedative plasma
      concentrations in children.

PMID- 1990899
TI  - Oxygen uptake after major abdominal surgery: effect of clonidine.
AB  - To examine the effect of an alpha-2 agonist, clonidine, on oxygen uptake and on
      the incidence of postoperative shivering, 28 patients presenting for major
      abdominal surgery were randomly assigned in a double-blind manner to one of two
      groups. Intraoperatively, 14 patients received 5 micrograms.kg-1 clonidine
      infused over 3 h (clonidine group), and 14 patients received placebo (placebo
      group). Oxygen uptake was measured continuously over the first 3 postoperative
      hours with a mass spectrometer system. Circulatory variables, esophageal
      temperature, and skin temperature were measured over the first 6 postoperative
      hours. Heart rate, mean arterial pressure, rate pressure product, and
      norepinephrine concentration were decreased in the clonidine group (P less than 2
      x 10(-4)). There were no differences among groups in the incidence of shivering
      and in the rate of increase of esophageal temperature. By contrast, oxygen uptake
      was lower in the clonidine group (P = 4 x 10(-4)). This contrasting pattern may
      be secondary to a reduction in the intensity of mean muscular tremor in the
      clonidine group.

PMID- 1990900
TI  - A comparison of obstetric and nonobstetric anesthesia malpractice claims.
AB  - Malpractice claims filed against anesthesiologists for care involving obstetric
      (OB) anesthesia (n = 190) were taken from the American Society of
      Anesthesiologists' Closed Claims Database and compared to claims not involving OB
      cases (n = 1351). The most common complications in the OB claims were (percentage
      of all OB claims): maternal death (22%), newborn brain damage (20%), and headache
      (12%). In contrast, the most common complications in the nonobstetric (non-OB)
      group were (percentage of all non-OB claims): death (39%), nerve damage (16%),
      and brain damage (13%). The group of OB claims contained a proportionately
      greater number of minor injuries, such as headache, backache, pain during
      anesthesia, and emotional injury (32%) compared to the non-OB claims (4%).
      Complications due to aspiration and convulsions were more common among the OB
      cases. The standard of care was judged to have been met in 46% of OB and 39% of
      non-OB claims. This difference is not statistically significant. Claims involving
      general anesthesia were more frequently associated with severe injuries and
      resulted in higher payments than did claims involving regional anesthesia.
      Payments were made in a similar proportion of OB and non-OB claims (53 and 59%,
      respectively). For cases in which payments were made, the median payment for OB
      claims was significantly greater ($203,000) than for non-OB claims ($85,000; P
      less than or equal to 0.05).

PMID- 1990901
TI  - The effect of age on systemic absorption and systemic disposition of bupivacaine
      after subarachnoid administration.
AB  - In order to evaluate the role of the pharmacokinetics of the age-related changes
      in the clinical profile of spinal anesthesia with bupivacaine, we studied the
      influence of age on the systemic absorption and systemic disposition of
      bupivacaine after subarachnoid administration in 20 male patients (22-81 yr), ASA
      Physical Status 1 or 2, by a stable isotope method. After subarachnoid
      administration of 3 ml 0.5% bupivacaine in 8% glucose, a deuterium-labeled analog
      (13.4 mg) was administered intravenously. Blood samples were collected for 24 h.
      Plasma concentrations of unlabeled and deuterium-labeled bupivacaine were
      determined with a combination of gas chromatography and mass fragmentography.
      Biexponential functions were fitted to the plasma concentration-time data of the
      deuterium-labeled bupivacaine. The systemic absorption was evaluated by means of
      deconvolution. Mono- and biexponential functions were fitted to the data of
      fraction absorbed versus time. The maximal height of analgesia and the duration
      of analgesia at T12 increased with age (r = 0.715, P less than 0.001; r = 0.640,
      P less than 0.01, respectively). In 18 patients the systemic absorption of
      bupivacaine was best described by a biexponential equation. The half-life of the
      slow systemic absorption process (r = -0.478; P less than 0.05) and the mean
      absorption time (r = -0.551; P less than 0.02) decreased with age. The total
      plasma clearance decreased with age (r = -0.650, P less than 0.002), whereas the
      mean residence time and terminal half-life increased with age (r = 0.597, P less
      than 0.01; r = 0.503, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1990902
TI  - Closed-loop infusion of atracurium with four different anesthetic techniques.
AB  - A new proportional-integral-derivative (PID) controller for the automated closed
      loop delivery of atracurium was tested in 32 patients. Groups of 8 patients
      received halothane, enflurane, isoflurane, or N2O/morphine anesthesia. After
      induction of anesthesia with sodium thiopental 3-5 mg.kg-1, a bolus of atracurium
      0.2 mg.kg-1 was delivered by the controller; this was followed by an infusion
      calculated by the controller to maintain the electromyogram (EMG) at a setpoint
      of 90% neuromuscular blockade. The average overshoot for the controller was 10.1%
      and the mean steady-state error 3.0%. The mean infusion rates for atracurium to
      maintain 90% blockade were calculated for each anesthetic group, with the
      inhalation anesthetics at 1 MAC. Infusion rates for N2O/morphine, halothane 0.8%,
      enflurane 1.7%, and isoflurane 1.4% at 90% blockade were 5.7 +/- 0.6, 4.9 +/-
      0.3, 3.5 +/- 0.3, and 4.1 +/- 0.5 micrograms.kg-1.min-1, respectively (mean +/-
      SE). The infusion rate for atracurium at 90% blockade under N2O/morphine
      anesthesia was in general agreement with published values. The other infusion
      rates at 90% blockade have not been reported previously, but correspond to the
      known potencies of these inhalation anesthetics for augmentation of neuromuscular
      blockade. This controller performed well in comparison to previously developed
      controllers, and in addition was used as a research tool for rapid estimation of
      infusion rates.

PMID- 1990903
TI  - The effects of halothane, enflurane, and isoflurane on the length-tension
      relation of the isolated ventricular papillary muscle of the ferret.
AB  - The effects of halothane, enflurane, and isoflurane on the length-tension
      relation were investigated in papillary muscles of the right ventricle of adult
      male ferrets at 30 degrees C. Isometric twitch contractions were obtained at
      lengths ranging from the shortest length yielding the greatest active force
      development under isometric conditions (Lmax) to 86% of Lmax, in two consecutive
      protocols: first in [Ca2+]o ranging from 0.45 to 2.25 mM, and then in [Ca2+]o
      2.25 mM before, during, and after exposure to incremental concentrations of
      halothane (n = 9 muscles), enflurane (n = 9 muscles), and isoflurane (n = 9
      muscles), each in steps of 0.25 MAC to total concentrations up to and including
      1.5 MAC. Each of the three anesthetics caused a concentration-dependent decrease
      in developed force. The relative extent of the negative inotropic effect was not
      different at various muscle lengths. Because myofibrillar Ca2+ responsiveness
      (Ca2(+)-affinity of troponin C) decreases at shorter muscle lengths, the results
      suggest that an alteration in myofibrillar Ca2+ responsiveness by volatile
      anesthetics is minor relative to the anesthetic-induced decreased intracellular
      Ca2+ availability in ventricular myocardium.

PMID- 1990904
TI  - Effects of enflurane and isoflurane on hepatic and renal circulations in
      chronically instrumented dogs.
AB  - Seven dogs were chronically instrumented for measurements of mean aortic blood
      pressure and cardiac output and for simultaneous measurements of hepatic, portal,
      and renal blood flows. Each animal was studied on two separate occasions, awake
      and during 1.2, 1.4, 1.75, and 2.0 MAC isoflurane and enflurane. Both anesthetics
      induced tachycardia; to a greater degree than isoflurane, enflurane lowered mean
      aortic blood pressure in a dose-dependent manner (-37, -45, -48, and -62% vs. 
      19, -25, -41, and -44%, respectively) and cardiac output (-20, -26, -41, and -48%
      vs. -3, -5, -11, and -15%, respectively). With isoflurane, cardiac output
      decreased only at 1.75 and 2.0 MAC, and portal blood flow did not change
      significantly, whereas hepatic arterial blood flow increased at 1.75 and 2 MAC
      (by 28 and 33%, respectively). With enflurane, no significant changes were
      recorded in hepatic arterial blood flow, whereas portal blood flow decreased in a
      dose-dependent manner. Except at 2 MAC, hepatic circulation did not differ
      between anesthetics. Likewise, neither anesthetic significantly changed renal
      blood flow, except for enflurane at 2.0 MAC, which was associated with a 35%
      reduction. Both anesthetics led to similar systemic, hepatic, and renal
      vasodilations. Our data suggest that high concentrations of enflurane are
      associated with decreases in portal, total hepatic, and renal blood flows, most
      likely as a result of an anesthetic-induced cardiac depression.

PMID- 1990905
TI  - Beneficial effect of upper thoracic epidural anesthesia in experimental
      hemorrhagic shock in dogs: influence of circulating catecholamines.
AB  - The question as to whether reduction of plasma catecholamine concentration
      contributes to the beneficial effects of upper thoracic epidural anesthesia on
      survival during hemorrhagic shock was examined. Twenty-six dogs were anesthetized
      with halothane and nitrous oxide, and blood was withdrawn to reduce the mean
      arterial blood pressure (MAP) to 40 mmHg. The 12 dogs in group A received both
      upper thoracic epidural anesthesia before the hemorrhage and intravenous infusion
      of epinephrine (450 ng.kg-1.min-1) and norepinephrine (150 ng.kg-1.min-1) during
      hemorrhage. The 14 dogs in group B received none of these. At 20 min after the
      start of the bleeding, plasma catecholamine concentrations were increased in both
      groups more than ten-fold. There were no significant intergroup differences with
      respect to these concentrations at any point during the experimental period.
      During the 100-min period of hemorrhage, 1 of the 12 animals in group A and 10 of
      the 14 in group B died. A significant difference in survival was seen between the
      two groups over the 100-min hypotensive period (P less than 0.01 by the
      generalized Wilcoxon test). These results suggest that the survival benefit of
      upper thoracic epidural anesthesia cannot be explained simply by differences in
      the level of catecholamines in the plasma, and that perhaps differences in the
      level of catecholamines at the nerve endings or other factors may be more
      important.

PMID- 1990906
TI  - Phlebotomy reverses the hemodynamic consequences of thoracic aortic cross
      clamping: relationships between central venous pressure and cerebrospinal fluid
      pressure.
AB  - In dogs (n = 11) anesthetized with sodium pentobarbital (to an isoelectric EEG),
      the authors investigated the influence of thoracic aortic cross-clamping (AXC) on
      systemic hemodynamics and cerebrospinal fluid pressure (CSFP) with concurrent
      measurement of total brain flow (tCBF) and regional (cervical, thoracic, and
      lumbar) spinal cord blood flow (SCBF). The effect of phlebotomy (to control the
      hemodynamic consequences of AXC) on tCBF and SCBF was assessed. Radioactive
      microspheres were injected at four time periods in each animal: 1) at baseline;
      2) with application of the AXC; 3) after phlebotomy, to reduce the proximal mean
      arterial pressure (MAPp) to baseline values; and 4) 2 min after removal of the
      AXC (mean AXC time 68 +/- 6 min). With application of the AXC, the MAPp, central
      venous pressure (CVP), and CSFP significantly increased (104 +/- 6 to 156 +/- 6
      mmHg, 3.4 +/- 0.4 to 5.2 +/- 0.7 mmHg, and 3.3 +/- 0.7 to 5.2 +/- 0.8 mmHg,
      respectively), while distal mean aortic pressure (MAPd) significantly decreased
      (98 +/- 6 to 14 +/- 1 1 mmHg). Phlebotomy (24 +/- 3 ml.kg-1) significantly
      decreased MAPp (to 106 +/- 6 mmHg), CVP (to 1.6 +/- 0.6 mmHg), and CSFP (to 1.2
      +/- 1.1 mmHg). The CSFP changed in parallel with the changes in CVP, a result
      suggesting that the alterations in CSFP depended on cardiac preload. The spinal
      cord perfusion pressure (SCPP; SCPP = MAPd - CSFP) was unchanged after
      phlebotomy, since both MAPd and CSFP decreased. The tCBF and cervical SCBF were
      unchanged when MAPp increased by 50% with application of the AXC; this indicated
      that autoregulation was intact.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1990907
TI  - Halothane, enflurane, and isoflurane depress the peripheral vagal motor pathway
      in isolated canine tracheal smooth muscle.
AB  - Volatile anesthetics are potent bronchodilators, but the site of action for the
      dilation is unclear. To determine the site of action of halothane, enflurane, and
      isoflurane on the peripheral vagal motor pathway, isolated strips of canine
      trachealis muscle were stimulated before and during exposure to halothane at 0.3,
      1.0, 1.7, or 2.4 MAC, enflurane at 1 MAC, or isoflurane at 1 MAC. The sites and
      methods of stimulation were: 1) postsynaptic nicotinic cholinergic receptors in
      the intramural parasympathetic ganglia, with 1,1-dimethyl-4-phenyl-piperazinium
      iodide (DMPP); 2) postganglionic cholinergic nerve fibers, with electrical field
      stimulation (EFS); and 3) muscarinic cholinergic receptors of the smooth muscle,
      with acetylcholine (ACh). The concentration-response curve to DMPP was
      significantly shifted to the right by 0.3 MAC halothane, whereas 0.3 MAC
      halothane had no significant effect on the concentration-response curves to ACh
      and EFS. At concentrations greater than 1 MAC of halothane, enflurane, or
      isoflurane, concentration-response curves to all three stimuli were shifted
      significantly to the right; i.e., the contractile responses to ACh, EFS, and DMPP
      were reduced. At all concentrations of halothane the force of contraction was
      significantly more reduced during stimulation with DMPP than during stimulation
      with ACh, and at halothane concentrations greater than or equal to 1.7 MAC the
      response to EFS was significantly more reduced than that to ACh. We conclude that
      halothane, enflurane, and isoflurane attenuated airway constriction by several
      mechanisms, including 1) reduced excitability of the postsynaptic nicotinic
      receptors of the intramural parasympathetic ganglia and 2) an effect on the
      smooth muscle and/or on the muscarinic receptors.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1990908
TI  - Influence of epinephrine on systemic, myocardial, and cerebral acid-base status
      during cardiopulmonary resuscitation.
AB  - During cardiopulmonary resuscitation (CPR), arterial pH and carbon dioxide
      tension (PCO2) do not reflect the marked acidosis and hypercapnia seen in venous
      blood samples during CPR. Epinephrine causes an increase in myocardial and
      cerebral blood flow during CPR, but the influence on regional venous PCO2 and pH
      is as yet unknown. Fourteen pigs were allocated to receive either 0.9% saline (n
      = 7), or 45 micrograms/kg epinephrine (n = 7) after 5 min of ventricular
      fibrillation and 3 min of open-chest CPR. Blood samples were obtained during CPR
      from the aorta, pulmonary artery, great cardiac vein, and sagittal sinus before
      and 90 s and 5 min after drug administration. Regional blood flow was measured
      with tracer microspheres. Plasma catecholamines were quantified by high
      performance liquid chromatography in arterial blood. PCO2 90 s after drug
      administration in arterial, mixed venous, myocardial venous, and cerebral venous
      blood were (means +/- SD) 36 +/- 8, 67 +/- 9, 74 +/- 14, and 79 +/- 19 mmHg in
      the control group and 35 +/- 11, 62 +/- 12, 73 +/- 10, and 71 +/- 14 mmHg in the
      epinephrine group. pH values 90 s after drug administration in the same blood
      samples were 7.29 +/- 0.11, 7.11 +/- 0.09, 7.04 +/- 0.09, and 7.07 +/- 0.10 in
      the control group and 7.31 +/- 0.13, 7.17 +/- 0.07, 7.08 +/- 0.08, and 7.07 +/-
      0.12 in the epinephrine group. Despite a significant increase in myocardial and
      cerebral blood flow after epinephrine, PCO2 and pH in all blood samples were not
      different from those of the control group. (ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1990909
TI  - Perioperative management of surgical patients with diabetes mellitus.

PMID- 1990910
TI  - High-efficiency delivery of salbutamol with a metered-dose inhaler in narrow
      tracheal tubes and catheters.
AB  - We sought to determine the percent delivery by metered-dose inhaler (MDI) of a
      preparation of salbutamol (albuterol) to the distal end of either pediatric-size
      tracheal tubes or a narrow-gauge catheter. A bench model consisting of a swivel
      actuator; 3.0-6.0-mm ID tracheal tubes all 16 cm in length or a 19-G (standard
      wire gauge) catheter; mesh filters; and a continuous flow of dry air was used.
      Six actuations of salbutamol (100 micrograms each) were delivered during each
      experiment, and each experiment was repeated nine times. The delivery efficiency
      (DE) was the ratio of the net increase in weight of the filter, positioned at the
      distal end of the tracheal tube, to the net weight increase of the entire
      apparatus. We found that the DE (mean +/- SD) of salbutamol at the end of the
      tracheal tube was significantly less with a 3.0-mm ID tube (2.5 +/- 7.0%) than it
      was with a 4.0-mm (10.8 +/- 8.3%), 5.0-mm (10.7 +/- 7.2%), or 6.0-mm (12.3 +/-
      8.4%) tube (P less than 0.05). To improve the DE of salbutamol aerosol, a 19-G
      catheter (0.7 mm ID) was inserted through the elbow connector and passed down the
      tracheal tube until the tip of the catheter approximated the distal tip of the
      tube. The DE of salbutamol in tracheal tubes (less than or equal to 12.3%)
      increased dramatically (97%; P less than 0.001) when a 19-G catheter was used. We
      conclude that the DE of salbutamol by MDI through 3.0-6.0-mm ID tracheal tubes is
      low but may be dramatically increased by actuating the canister into a 19-G
      distally placed catheter. Because of the increased efficiency of delivery,
      caution must be exercised when using a distally placed catheter to deliver MDI
      aerosols to patients.

PMID- 1990911
TI  - Protein C deficiency as a cause of pulmonary embolism in the perioperative
      period.

PMID- 1990912
TI  - Complication from a nasopharyngeal airway in a patient with a basilar skull
      fracture.

PMID- 1990913
TI  - Axillary block for vascular insufficiency after repair of radial club hands in an
      infant.

PMID- 1990914
TI  - Nominal hemoptysis heralds pseudoaneurysm induced by a pulmonary artery catheter.

PMID- 1990915
TI  - Successful anesthetic management of a patient with hypokalemic familial periodic
      paralysis undergoing cardiac surgery.

PMID- 1990916
TI  - Ventricular pacing can induce hemodynamically significant mitral valve
      regurgitation.

PMID- 1990917
TI  - Truncus arteriosus: recognition and therapy of intraoperative cardiac ischemia.

PMID- 1990918
TI  - Mechanical chin support during radiotherapy.

PMID- 1990919
TI  - Insufflation anesthesia for suture removal after cheiloplasty.

PMID- 1990920
TI  - Nitrous oxide abuse presenting as premature exhaustion of Sodasorb.

PMID- 1990921
TI  - If ventricular conduction and rhythm disorders are caused by bupivacaine, it is
      doubtful that intraoperative hyponatremia and hyperkalemia enhance them.

PMID- 1990922
TI  - Termination of hiccups occurring under anesthesia.

PMID- 1990923
TI  - Benzocaine and methemoglobin: recommended actions.

PMID- 1990924
TI  - A double-lumen endobronchial tube for tracheostomies.

PMID- 1990925
TI  - Nystagmus following epidural morphine.

PMID- 1990927
TI  - Getting the bugs out.

PMID- 1990926
TI  - Routine testing for latex allergy in patients with spina bifida is not
      recommended.

PMID- 1990928
TI  - Difficult pulmonary artery catheterization in the patient with tricuspid
      regurgitation.

PMID- 1990929
TI  - The pulmonary academic "transitional track". A view from a minority faculty.

PMID- 1990930
TI  - Variability of the respiratory gas exchange ratio during arterial puncture.
AB  - The value of R, the respiratory gas exchange ratio, was determined in 70
      unselected outpatients while undergoing arterial blood sampling as part of
      routine pulmonary function testing. We wished to determine whether acute changes
      in alveolar ventilation occurring during blood drawing were of sufficient
      magnitude to cause a significant error in the calculation of alveolar PO2 if the
      value of 0.80 for R was assumed. In the majority of subjects, R ranged from 0.70
      to 0.90. In approximately 25% of the cases, the assumption of the value of 0.80
      for R would have led to an error equal to or greater than 10 mm Hg in the
      estimation of the alveolar-arterial PO2 difference.

PMID- 1990931
TI  - Mechanisms of gas-exchange impairment in idiopathic pulmonary fibrosis.
AB  - To investigate the mechanisms of pulmonary gas-exchange impairment in idiopathic
      pulmonary fibrosis (IPF) and to evaluate their potential relationship to the CO
      diffusing capacity (DLCO), we studied 15 patients with IPF (mean DLCO, 52% of
      predicted) at rest (breathing room air and pure O2) and during exercise. We
      measured pulmonary hemodynamics and respiratory gas-exchange variables, and we
      separated the ventilation-perfusion (VAQ) mismatching and O2 diffusion limitation
      components of arterial hypoxemia using the multiple inert gas elimination
      technique. At rest VA/Q mismatching was moderate (2 to 4% of cardiac output
      perfusing poorly or unventilated lung units), and 19% of AaPO2 was due to O2
      diffusion limitation. During exercise VA/Q mismatch did not worsen but the
      diffusion component of arterial hypoxemia increased markedly (40% AaPO2, p less
      than 0.005). We observed that those patients with higher pulmonary vascular tone
      (more release of hypoxic pulmonary vasoconstriction) showed less pulmonary
      hypertension during exercise (p less than 0.05), less VA/Q mismatching [at rest
      (p less than 0.005) and during exercise (p less than 0.0025)], and higher
      arterial PO2 during exercise (p = 0.01). We also found that DLCO corrected for
      alveolar volume (KCO) correlated with the mechanisms of hypoxemia during exercise
      [VA/Q mismatching (p less than 0.025) and O2 diffusion limitation (p less than
      0.05)] and with the increase in pulmonary vascular resistance elicited by
      exercise (p less than 0.005). In conclusion, we showed that the abnormalities of
      the pulmonary vasculature are key to modulate gas exchange in IPF, especially
      during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1990932
TI  - Ventilation and gas exchange during exercise in sickle cell anemia.
AB  - Adults with sickle cell anemia (SCA) have restrictive lung impairment, increased
      alveolar dead space, and hypoxemia. These factors, together with increased
      anaerobic metabolism, are thought to cause exercise hyperventilation. To assess
      the role of each of these in children, 34 patients with SCA and 16 control
      subjects performed pulmonary function and exercise tests. Twenty-eight patients
      with SCA had spirometric values and lung volumes, and all but two patients with
      SCA had arterial saturation greater than 91% during exercise. Despite a low
      VO2max (30.07 +/- 6.55 ml/min/kg), the ventilatory anaerobic threshold (VAT) in
      the patients occurred at a similar %VO2max as in the control subjects (69 +/- 9%
      versus 63 +/- 12%). The slope of the delta VE/delta VCO2 relationship for sub-VAT
      work was steeper in the patients (29.4 +/- 6.5 versus 24.7 +/- 5.2, p = 0.01),
      and the ventilatory equivalent for CO2 (VE/VCO2) in steady-state exercise was
      greater in the patients than in the control subjects (33.2 +/- 3.5 versus 30.8 +/
      3.5, p = 0.03). End-tidal PCO2 did not differ (38.3 +/- 3.0 versus 39.2 +/-
      3.1), indicating equivalent alveolar ventilation. The patients had a higher dead
      space:tidal volume ratio (VD/VT) than did the control subjects (0.204 +/- 0.033
      versus 0.173 +/- 0.024, p = 0.0005). The PaCO2 was significantly lower in those
      with lower Hb, but there was no difference in pH. In conclusion, children with
      SCA have an increased exercise ventilatory response caused in part by increased
      physiologic dead space, and in part by their low Hb. The greater dead space may
      be the result of sickle cells impairing capillary perfusion to ventilated
      alveoli.

PMID- 1990933
TI  - Cardiac output and oxygen delivery during exercise in sickle cell anemia.
AB  - Desaturation in patients with sickle cell anemia (SCA) can lead to intravascular
      sickling and vascular occlusion. The increased metabolic demands of exercise tend
      to increase oxygen extraction, giving rise to a fall in saturation in the
      capillary bed that may predispose to sickling. This could be minimized with an
      increase in cardiac output. The aims of this study were to assess the role of
      increased stroke volume (SV) in augmenting cardiac output (Q) and to estimate the
      role of enlarged arteriovenous O2 content difference in maintaining O2 transport
      in children with SCA. A group of 30 children with SCA (Hb 65 to 133 g/L) and 16
      healthy controls of the same racial group and of similar height and weight
      performed incremental and steady-state exercise at 50% Wmax. Cardiac output (Q)
      was measured by the indirect (CO2) Fick method during steady state. The slope of
      delta HR/delta VO2 during incremental exercise was higher in SCA subjects
      compared with controls (4.01 +/- 1.73 versus 2.80 +/- 0.61 bpm per ml/min/kg VO2,
      p = 0.001). Q for VO2 was abnormally high in patients, particularly older ones
      with lower Hb levels. HR (% predicted) was higher in patients than in controls
      (106 +/- 11 versus 92 +/- 8% predicted, p less than 0.0001), as was SV (113 +/-
      16 versus 98 +/- 14% predicted, p = 0.002). Multiple linear regression of Q %
      predicted and SV % predicted on Hb and age showed a positive correlation with age
      and a negative correlation with Hb (r = 0.84 for Q and r = 0.76 for SV).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1990934
TI  - Closure of the ductus arteriosus with indomethacin in ventilated neonates with
      respiratory distress syndrome. Effects of pulmonary compliance and ventilation.
AB  - The reported effects of indomethacin on pulmonary compliance are variable
      depending upon the patient population and on the degree to which indomethacin
      resulted in successful ductal closure. Eleven fluid-restricted, furosemide
      treated premature infants being mechanically ventilated for respiratory distress
      syndrome (RDS) who also had a significant patent ductus arteriosus (PDA) had
      pulmonary function testing performed before and after successful closure of the
      PDA. The diagnosis of a significant PDA was made by clinical and
      echocardiographic criteria. Indomethacin was administered at a dosage of 0.2
      mg/kg/dose every 12 to 18 h for 1 to 3 doses. To control for the 48-h time
      interval to achieve ductal closure, nine premature infants being ventilated for
      RDS but who did not have a significant PDA also had pulmonary function
      evaluations performed before and after the 48 h. Also, to control for the
      independent effect of fluid restriction and diuretic therapy on pulmonary
      compliance, eight such premature infants with a PDA had pulmonary function
      evaluations performed at a 48-h interval. Successful closure of the ductus with
      indomethacin was associated with an improvement in compliance and ventilation
      parameters in all infants in the indomethacin-treated infants. In the
      indomethacin-treated group, the mean percent improvements were noted in the
      following parameters: CLdyn, 59.2%; CLI, 78.3%; CLE, 63.3%; VT, 63.3%; VE, 54.6%.
      There were no significant changes in the pulmonary functions in the 48-h RDS or
      the 48-h PDA fluid-restricted, furosemide-treated control groups. In conclusion,
      successful closure of the ductus with indomethacin causes a significant
      improvement in compliance and ventilation parameters in infants being
      mechanically ventilated for RDS.

PMID- 1990935
TI  - Dependencies of respiratory system resistance and elastance on amplitude and
      frequency in the normal range of breathing.
AB  - We calculated respiratory system resistance (Rrs) and elastance (Ers) from
      pressure and flow at the mouth in six seated subjects relaxed at FRC (cheeks
      tightly compressed) during sinusoidal volume forcing (250, 500, and 750 ml) at
      0.2, 0.4, and 0.6 Hz. Dependencies of Rrs and Ers on frequency and tidal volume
      were generally the same in each subject; Rrs tended to decrease with frequency
      and tidal volume, whereas Ers tended to increase with frequency and decrease with
      tidal volume. Multiple linear regression of combined data indicated that the
      frequency and tidal volume effects on Rrs and Ers were significant (p less than
      0.05), and that the effects on Rrs decreased at higher flows. Average Rrs was
      highest (4.43 cm H2O/L/s +/- 0.21 SE) at 0.2 Hz-250 ml, and lowest (3.07 cm
      H2O/L/s +/- 0.37) at 0.6 Hz-750 ml. Average Ers was highest (12.1 cm H2O/L +/-
      1.1) at 0.6 Hz-250 ml, and lowest (7.1 cm H2O/L +/- 0.6) at 0.2 Hz-750 ml. We
      conclude that frequency and tidal volume dependencies in Rrs and Ers in the
      normal range of breathing should be considered when interpreting measurements of
      respiratory system impedance or developing models to describe the mechanical
      behavior of the respiratory system.

PMID- 1990936
TI  - Pneumocystis carinii pneumonia and respiratory failure in AIDS. Improved outcomes
      and increased use of intensive care units.
AB  - To determine whether the outcome of intensive care for patients with AIDS,
      Pneumocystis carinii pneumonia (PCP), and respiratory failure has changed, we
      studied patients admitted to the intensive care units an San Francisco General
      Hospital from 1981 to 1988. We compared the course of patients with PCP and
      respiratory failure admitted to the intensive care unit from 1986 to 1988 with a
      similar cohort hospitalized from 1981 to 1985. The hospital survival rate for the
      35 patients in the 1986 to 1988 cohort was 40%, compared with 14% for the 42
      patients in the 1981 to 1985 cohort (p less than 0.01). Age, episode of PCP, time
      since AIDS diagnosis, anti-PCP therapy, and important clinical variables were
      similar in both cohorts. Corticosteroids were used commonly in the recent era.
      Patients who received steroids had an in-hospital survival rate of 46%, compared
      with 22% for those who did not receive steroids (p = NS). In a stepwise logistic
      regression model, ICU care in the recent era and higher serum albumin at the time
      of ICU admission were the only variables significantly associated with survival.
      The hospital survival of patients with PCP and respiratory failure has improved.
      The improvement could not be explained by patient selection or by better anti-PCP
      therapy. The apparent beneficial effect of corticosteroids deserves further
      study. The improvement in ICU outcome was reflected in increased ICU utilization
      by patients with AIDS, PCP, and respiratory failure.

PMID- 1990937
TI  - An outbreak of tuberculosis in a shelter for homeless men. A description of its
      evolution and control.
AB  - An outbreak of tuberculosis at a shelter for homeless men was studied in detail
      to further the understanding of the epidemiology of tuberculosis in this setting.
      The shelter provides evening accommodations for men aged 50 yr and older. The
      capacity is approximately 200 clients, and the client pool is approximately 1,000
      men/yr. During a 6-wk period in December 1986 and January 1987, seven cases of
      tuberculosis were diagnosed in shelter clients. Nine cases were reported in
      clients during the preceding 12 months, and four cases in the year previous to
      that. The majority of outbreak cases were pulmonary tuberculosis, sputum smear
      positive. Drug resistance was rare. Phage typing of 15 Mycobacterium tuberculosis
      isolates revealed one predominant type and four other types. The goals of the
      control plan (and the steps taken to achieve them) were to render known
      infectious cases noninfectious (directly observed therapy); to find undiagnosed
      infectious cases (repetitive mass screenings); to protect exposed clients
      (repetitive tuberculin skin testing and isoniazid preventive therapy); and to
      make the shelter environment safe (exclude infectious, noncompliant clients and
      improve the shelter's ventilation system). Implementation of this plan rapidly
      terminated the outbreak; following the first mass screening in January 1987, at
      which six asymptomatic cases were detected, only five additional cases occurred
      in shelter clients during a 2-yr period of follow-up. The investigation suggested
      that the outbreak evolved during 1986 as a result of the presence at the shelter
      of an increasing number of men with undiagnosed infectious pulmonary
      tuberculosis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1990938
TI  - A controlled clinical comparison of 6 and 8 months of antituberculosis
      chemotherapy in the treatment of patients with silicotuberculosis in Hong Kong.
      Hong Kong Chest Service/tuberculosis Research Centre, Madras/British Medical
      Research Council.
AB  - Patients with silicotuberculosis have been reported to respond poorly to
      antituberculosis chemotherapy. Therefore, in a study in Hong Kong, 240 Chinese
      male patients with both silicosis and pulmonary tuberculosis were all prescribed
      treatment three times weekly with streptomycin, isoniazid, rifampin, and
      pyrazinamide, allocated at random to be given for a total duration of either 6
      (M6 regimen) or 8 months (M8 regimen) in a concurrent comparison. Those with a
      history of previous antituberculosis chemotherapy received ethambutol as well for
      the first 3 months. The intake in the M6 regimen was terminated when preliminary
      results showed that it was inadequate, and a further 53 patients were assigned to
      the M8 series. Of 91 assessable patients in the concurrent comparison with
      susceptible strains pretreatment, 44% were culture negative at 1 month, 80% at 2
      months, and 98% at 3 months, and 1 had an unfavorable bacteriologic response
      during chemotherapy. During 3 yr of assessment, bacteriologic relapse after
      chemotherapy occurred in 22% of the M6 compared with 7% of the M8 patients (p
      less than 0.025, log-rank test). Inadequate chemotherapy was received by 12% of
      the 240 patients in the concurrent comparison because of default and by 22%
      because of adverse effects, but by 3 yr 92% of patients with susceptible strains
      pretreatment in each series had a favorable status following retreatment for
      relapse or for initially inadequate chemotherapy when required. The results show
      that patients with silicosis require at least 8 months of treatment.

PMID- 1990939
TI  - Increased levels of oxidized methionine residues in bronchoalveolar lavage fluid
      proteins from patients with idiopathic pulmonary fibrosis.
AB  - Phagocytic cells are believed to play a crucial role in the development of
      inflammatory lung diseases. We assumed that the oxidation of methionine (met) to
      methionine sulfoxide [met(O)] by oxygen-derived free radicals released from
      phagocytes is one parameter to identify the oxidative mechanisms of lung injury.
      To test this hypothesis we determined the molar ratio of met(O)/met in the
      soluble protein fraction of bronchoalveolar lavage (BAL) fluids from healthy
      nonsmokers and from nonsmoking patients with idiopathic pulmonary fibrosis (IPF)
      or sarcoidosis. The met(O)/met ratio of the healthy nonsmoker group (n = 11) was
      0.046 +/- 0.008 (mean +/- SEM). In contrast, the met(O)/met ratio of the
      nonsmoking IPF group (n = 11) was significantly increased to 0.223 +/- 0.053 (p
      less than 0.0002). The BAL fluids of this group showed strongly increased numbers
      of neutrophils but normal numbers of alveolar macrophages (AM). In the
      sarcoidosis group (n = 10) the met(O)/met ratio (0.048 +/- 0.010) was not
      significantly different from control values. A close relationship was found
      between the met(O)/met ratios and the relative as well as the absolute neutrophil
      counts (r = 0.86; p less than 0.0002; n = 22). In contrast, no significant
      correlation was found between the met(O)/met ratios and the absolute AM counts (r
      = 0.22; p = 0.32; n = 22). We conclude that mechanisms of oxidative lung injury
      in IPF can be characterized by oxidation of met and that this oxidation may be
      mediated by neutrophils.

PMID- 1990940
TI  - Immunoglobulin G antineutrophil cytoplasmic antibodies are produced in the
      respiratory tract of patients with Wegener's granulomatosis.
AB  - Wegener's granulomatosis (WG) is a small-vessel vasculitis of unknown etiology
      that usually involves the upper and lower respiratory tract and the kidneys.
      Recently, an association has been made between the presence of serum
      antineutrophil cytoplasmic antibodies (ANCA) and WG. Because WG frequently
      involves the lung, we sought to evaluate bronchoalveolar lavage (BAL) fluids
      obtained from 14 patients with WG for the presence of ANCA. Immunoglobulin (Ig) G
      ANCA was found in the BAL with the same staining patterns as observed in the
      serum. Patients with active disease had the highest serum and BAL IgG ANCA
      titers. IgA or IgM ANCA was not detected in the serum or BAL of these patients.
      Protein analysis of BAL fluid revealed that patients with active, untreated WG
      had approximately a fourfold elevation in total protein (41.3 versus 10.5 mg/dl),
      with a disproportionately greater increase in the ratio of IgG to albumin (BAL
      IgG index = 1.49, normal = 0.74; p = 0.027). The increase of the IgG index in
      patients with active WG suggests that local production of IgG ANCA occurs in the
      lungs.

PMID- 1990941
TI  - Size distribution of human lung elastin-derived peptide antigens generated in
      vitro and in vivo.
AB  - The protease-antiprotease hypothesis of emphysema development suggests that
      degradation of elastin in the lung interstitium may give rise to abnormal
      quantities of circulating elastin-derived peptides (EDP) during periods of
      inflammation. Recent studies have shown a relationship between emphysema and high
      levels of EDP in human plasma. This report characterizes elastin digests on the
      basis of antigenicity, size, and method of preparation, as well as the size
      distribution of EDP found in the plasmas of nonsmokers, smokers, and emphysema
      patients. Gel filtration of elastin digests prepared by hydrolysis of human lung
      elastin using a low (1:500) ratio of neutrophil elastase to elastin generated a
      broad protein peak of approximately 70,000 daltons. In contrast, a high (1:25)
      ratio of neutrophil elastase to human lung elastin gave a broad protein peak,
      with a size distribution in the 10,000 to 30,000 dalton range. This digest showed
      distinct immunochemical properties. A polyclonal antibody directed against the
      low-ratio digest showed a minimum detection of 2 ng/ml for the homologous antigen
      but required 1,000 ng/ml of the high-ratio digest for detectable inhibition in an
      indirect ELISA assay. Gel filtration of plasmas from normal nonsmokers and the
      majority of normal smokers revealed a single immunoreactive EDP fraction of
      approximately 70,000 daltons. Plasmas from selected normal smokers and emphysema
      patients with high levels of circulating EDP (greater than 90 ng/ml) fractionated
      into a complex pattern of peptides in which the 70,000 dalton component
      represented 50% of the immunoreactive material and several lower molecular weight
      peptides represented the remaining circulating elastin antigens.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1990942
TI  - Comparison of the bronchopulmonary and pressor activities of endothelin isoforms
      ET-1, ET-2, and ET-3 and characterization of their binding sites in guinea pig
      lung.
AB  - In anesthetized and ventilated guinea pigs intravenous injection of ET-1, ET-2,
      or ET-3 (1 or 2 nmol/kg) induced similar dose-dependent increases in pulmonary
      inflation pressure (PIP) associated with increases in mean arterial blood
      pressure (MBP). Pretreatment of the guinea pigs with 1 mg/kg intravenous
      indomethacin significantly inhibited the increase in PIP evoked by 2 nmol/kg of
      ET-1, ET-2, or ET-3. In contrast, the increase in MBP following injection of the
      various ET isotypes was not significantly affected by indomethacin. Injection of
      ET-1, ET-2, or ET-3 (40, 120, and 400 pmol) via the pulmonary artery of isolated
      and perfused guinea pig lungs induced dose-dependent increases in PIP and
      pulmonary perfusion pressure (PPP), thromboxane B2 (TXB2) release, and formation
      of lung edema. In keeping with the in vivo results, no marked differences were
      observed between the activities of ET-1, ET-2, and ET-3 on isolated and perfused
      guinea pig lungs. Indomethacin (5 microM) added to the perfusion medium
      significantly inhibited the alterations of PIP and PPP, TXB2 release, and edema
      formation evoked by 400 pmol ET-1, ET-2, or ET-3. High-affinity binding sites for
      ET-1, ET-2, and ET-3 exhibiting similar characteristics were identified on guinea
      pig lung membrane. Therefore ET-1, ET-2, and ET-3 exert comparable
      bronchopulmonary and pressor activities in the guinea pig and probably act via
      interaction with the same binding site. In addition, the ET-induced increase in
      PIP and pulmonary vasoconstriction are primarily mediated via the production of
      cyclooxygenase metabolites.

PMID- 1990943
TI  - A ten-year follow-up study of cotton textile workers.
AB  - A follow-up study of respiratory function in cotton textile workers was performed
      10 yr after the original cross-sectional study (1975 to 1985). There were 35
      nonsmoking female and 31 smoking male textile workers restudied from the original
      group of 116. The majority of those lost to follow-up had left the industry. The
      prevalence of byssinosis among the female workers at the time of follow-up was
      15/35 (42.9%) compared with 8/35 (22.9%) at the time of the initial study (p =
      0.063). For men the byssinosis prevalence at follow-up was 16/31 (51.6%) compared
      with 8/31 (22.9%) at the time of the initial study (p = 0.03). Similarly, the
      prevalence of almost all other respiratory symptoms was significantly higher at
      the follow-up than at the time of the initial study. Significant across-shift
      decrements in FEV1 and FVC were documented at both surveys. The mean annual
      decline in ventilatory capacity was greater than expected for both female (FVC: 
      0.036 +/- 0.005 L/yr; FEV1: -0.059 +/- 0.009 L/yr) and male workers (FVC: -0.059
      +/- 0.008 L/yr; FEV1: -0.068 +/- 0.006 L/yr) (Mean +/- SE). The mean total
      airborne dust concentration measured at the time of the follow-up study was 3.95
      mg/m3 with an average respirable dust concentration of 0.97 mg/m3. We conclude
      that continued exposure to high dust concentrations in the cotton textile
      industry is associated with an increasing prevalence of respiratory symptoms and
      progressive impairment of lung function. The increase in respiratory impairment
      was seen both in smokers and nonsmokers.

PMID- 1990944
TI  - Relationship of respiratory symptoms and pulmonary function to tar, nicotine, and
      carbon monoxide yield of cigarettes.
AB  - The data from consecutive surveys of the Tucson Epidemiologic Study (1981-1988)
      were used to evaluate the relationship in cigarette smokers of respiratory
      symptoms and pulmonary function to tar, nicotine, and carbon monoxide (CO) yields
      of the cigarette. There were 690 subjects who reported smoking regularly in at
      least one survey, over age 15. After adjustment for intensity and duration of
      smoking and for depth of inhalation, the risk of chronic phlegm, cough, and
      dyspnea were not related to the tar and nicotine yields. In 414 subjects with
      pulmonary function tested in at least one of the three surveys the spirometric
      indices used were significantly related to the daily dose of tar, nicotine, and
      CO (product of the cigarette yield and daily number of cigarettes smoked). The
      effects were more pronounced for past than for current doses. However, the
      differentiation of pulmonary function due to various yields of cigarettes was
      small in comparison to the difference in pulmonary function between smokers and
      nonsmokers.

PMID- 1990945
TI  - Initial airway function is a risk factor for recurrent wheezing respiratory
      illnesses during the first three years of life. Group Health Medical Associates.
AB  - We recently reported a significant relationship between lung function measured
      prior to any lower respiratory tract illness and subsequent wheezing illnesses
      during the first year of life (N Engl J Med 1988; 319:1112-7). Follow-up has
      continued for this group of infants during the second and third years of life.
      When compared with never wheezers, infants who wheezed during the first year of
      life and had at least one additional lower respiratory illness had 22% lower
      initial levels of an indirect index of airway conductance derived from the shape
      of tidal breathing curves (p less than or equal to 0.01), 22% lower respiratory
      conductance (p less than or equal to 0.05), 25% lower maximal flows at the end
      expiratory point (p less than or equal to 0.01), and 10% lower functional
      residual capacity (p less than or equal to 0.05). Infants who wheezed only once
      during the first 3 yr of life or who started wheezing during the second year of
      life had normal tidal breathing curves but significantly lower maximal expiratory
      flows (p less than or equal to 0.05). Their functional residual capacity was also
      lower than that of never wheezers (p less than or equal to 0.05). We conclude
      that diminished initial airway function may be a predisposing factor for
      recurrent wheezing respiratory illnesses starting in the first year of life.
      Infants who will have only one wheezing respiratory illness or who will start
      wheezing after the first year of life seem to have lower levels for some but not
      for all lung function tests performed in this study.

PMID- 1990946
TI  - Bronchial responsiveness in a Norwegian community.
AB  - Bronchial responsiveness to methacholine was examined in a Norwegian general
      population sample (n = 490) 18 to 73 yr of age. Altogether, 20 and 6% of the
      sample had PC20 less than or equal to 32 mg/ml and PC20 less than or equal to 8
      mg/ml, respectively. The relationship of bronchial responsiveness to the
      following potential predictors were examined: sex, age, smoking habits, airway
      caliber (FEV1), FEV1 percent predicted (%FEV1), urban-rural area of residence,
      occupational airborne exposure in present job, and total serum IgE. After
      adjusting for age and FEV1, the odds ratio for PC20 less than or equal to 32
      mg/ml was higher for men than for women in smokers and in ex-smokers, but did not
      vary by sex in nonsmokers, the adjusted odds ratio for PC20 less than or equal to
      32 mg/ml in male compared with female smokers being 8.4 (95% Cl: 2.5-37.4).
      Irrespective of smoking status the sex- and FEV1-adjusted odds ratio for PC20
      less than or equal to 32 mg/ml fell with increasing age. For every 10-yr increase
      in age the adjusted odds ratio for PC20 less than or equal to 32 mg/ml
      methacholine in nonsmokers decreased by 2.0 (95% Cl: 1.3-3.3). Also FEV1 and
      %FEV1 were predictors of PC20 less than or equal to 32 mg/ml after adjusting for
      sex and age irrespective of smoking status. Bronchial responsiveness (PC20 less
      than or equal to 8 mg/ml) was more prevalent in rural than in urban areas, the
      adjusted odds ratio being 2.5 (95% Cl: 1.1-5.9) for bronchial responsiveness in
      rural compared with urban residents after adjusting for sex, age, smoking habits,
      and FEV1.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1990947
TI  - The normal range of diurnal changes in peak expiratory flow rates. Relationship
      to symptoms and respiratory disease.
AB  - Measuring peak expiratory flow rates (PEFR) several times a day can provide an
      objective assessment of functional changes relative to environmental or
      occupational exposures. This report describes the pattern of diurnal changes in
      PEFR in a reference population, and defines ranges of "normal" between- and
      within-day variability. An index of diurnal changes was defined as the ratio
      between maximal and minimal values, where the maximal value was restricted to
      PEFR measured at noon or in the evening (N, E) and the minimal value was
      restricted to the morning or at bedtime (M, B). A ratio greater than normal
      represented an exaggeration of the normal diurnal pattern in PEFR. Normal limits,
      based on the ninety-fifth percentile in the reference population, were larger for
      children (130%) than for adults 15 to 35 yr of age (117%) and those older than 35
      yr of age (118%). The meaningfulness of excessive diurnal changes in PEFR was
      examined by relating this ratio (Max/Min), and a similar measure (the amplitude
      percent mean) to chronic respiratory symptoms and diseases in 938 adults and
      children who recorded PEFR values 2 to 4 times per day for as long as 14 days.
      There was a strong relationship of diurnal changes in PEFR that exceed normal
      limits with physician-confirmed asthma (relative risk of 2.99 with Max/Min), with
      exertional dyspnea (Grade 2+), and with more frequent reporting of acute symptoms
      of wheeze, attacks of wheezing dyspnea, cough, and chest colds. In addition,
      those exceeding the normal limits had about 2.9 times greater risk of having a
      FEV1 below 80% of predicted, and nearly 7 times greater risk of being below
      70%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1990948
TI  - Allergen-induced asthmatic responses. Relationship between increases in airway
      responsiveness and increases in circulating eosinophils, basophils, and their
      progenitors.
AB  - The inflammatory response during allergen-induced asthma was assessed using
      serial measures of peripheral blood eosinophils (Eo), basophils (B), and Eo/B
      progenitor cells (Eo/B-CFU). A group of 14 stable asthmatic individuals (beta 2
      agonists only as needed) had inhalation provocation tests with allergen (18 tests
      in total) and with diluent. Serial blood samples were taken before and 1 and 24 h
      after the tests; methylcellulose cultures for Eo/B-CFU and granulocyte-macrophage
      (GM-CFU) were scored at 14 days. Circulating Eo, B, and Eo/B-CFU were increased
      at 24 h after allergen inhalation when this resulted in increased histamine
      airway responsiveness (n = 13). In the 5 subjects with isolated early asthmatic
      responses the Eo, B, and Eo/B-CFU counts did not change. There was no change in
      the GM-CFU after allergen. The ratio change in circulating Eo/B-CFU was
      negatively correlated with baseline histamine airway responsiveness (r = -0.8, p
      less than 0.05). Four subjects who had an isolated early response and no blood
      changes to one allergen developed an increase in histamine airway responsiveness
      and an increase in Eo, B, and Eo/B progenitors after inhalation of a second
      different allergen. The results indicate that in subjects with an allergen
      induced increase in histamine airway responsiveness, an inflammatory response
      occurs that includes an increase in the number of Eo/B progenitors. This
      response, possibly mediated by Eo/B growth and differentiation factors, could
      lead to the accumulation of these cells in the airway and contribute to the
      airways inflammation present in asthma.

PMID- 1990949
TI  - Asthma in the elderly. A comparison between patients with recently acquired and
      long-standing disease.
AB  - To characterize asthma in the elderly, 25 consecutive nonsmoking pulmonary clinic
      patients over the age of 70 who met the American Thoracic Society criteria for
      asthma were identified. Of these, 12 patients (48%) had developed asthma at an
      advanced age (greater than 65 yr). This group with late-onset asthma had a mean
      duration of disease of 5.1 +/- 2.5 yr. The remaining group with early-onset
      asthma had a mean duration of illness of 31.4 +/- 14.6 yr. On the day of
      evaluation each patient underwent pulmonary function testing off all medication
      for at least 12 h. These two groups were indistinguishable by symptoms and
      medication requirements. Immediate hypersensitivity skin testing to 43
      aeroallergens was uniformly negative in all 25 patients but the histamine control
      was always positive. IgE levels in both groups were not different from those in
      elderly control subjects. Those with early-onset asthma had a greater likelihood
      of previous allergic disease (p less than 0.001) and a significantly greater
      degree of airflow obstruction in pre- and postbronchodilator pulmonary function
      testing (p less than 0.05). This study suggests that long-standing asthma may
      lead to chronic persistent airflow obstruction and thereby mimic chronic
      bronchitis and emphysema (COPD).

PMID- 1990950
TI  - Inhalation of an alkaline aerosol by subjects with mild asthma does not result in
      bronchoconstriction.
AB  - Although it is recognized that inhalation of acid aerosols by subjects with
      asthma can cause bronchoconstriction, the effects of the inhalation of an
      alkaline aerosol are unknown. When supplemental inflatable restraints (automobile
      air bags) are deployed an alkaline aerosol is released. This aerosol is composed
      of particles of sodium carbonate and sodium bicarbonate with some sodium
      hydroxide. The mass median aerodynamic diameter (MMAD) of the aerosol is
      approximately 1 micron, and the pH of the aerosol is 9.8 to 10.3. A group of 14
      volunteer male subjects with mild asthma inhaled increasing concentrations of
      this aerosol for 20-min periods of mouth-only tidal ventilation. Pulmonary
      function tests were performed at baseline (preexposure), after inhalation of room
      air alone (control), and after each period of inhalation of the aerosol. A total
      of 5 subjects inhaled aerosols at nominal concentrations of 10, 20, and 40 mg/m3,
      whereas 11 subjects inhaled aerosols concentrations of approximately 30, 60, and
      120 mg/m3. The mean changes in FEV1 and specific airways resistance (SRaw) for
      the 11 subjects who inhaled the higher concentrations (average highest
      concentration 126.6 +/- 7.5 mg/m3, mean +/- SEM) were -1.4 +/- 1.9 and +17.5 +/-
      8.5%, respectively. Neither change in lung function was clinically or
      statistically significant. We conclude that the inhalation of relatively high
      concentrations of this alkaline aerosol by subjects with mild asthma does not
      result in bronchoconstriction.

PMID- 1990951
TI  - Protective effect of theophylline on bronchial hyperresponsiveness in patients
      with allergic rhinitis.
AB  - Disorders of the upper respiratory tract, particularly allergic rhinitis are
      commonly associated with bronchial hyperresponsiveness. The latter may be
      responsible for chronic cough, a common symptom in patients with allergic
      rhinitis, which, as previously shown, can be the sole presenting manifestation of
      bronchial hyperresponsiveness. Theophylline is widely used in patients with
      asthma for its bronchodilator effect, whereas its action on bronchial reactivity
      is controversial. The aim of this study was to determine the effect of
      theophylline administration on bronchial hyperresponsiveness in patients with
      allergic rhinitis complaining of chronic cough. Fourteen patients were studied.
      All of them were judged atopic on the basis of positive skin tests to common
      allergens. During control, spirometry, flow-volume curves and specific airway
      conductance (SGaw) were measured. Bronchial challenges were then performed with
      increasing concentrations of carbachol, and dose-response curves were
      constructed. The concentration of carbachol, which decreased SGaw by 35% from
      baseline (PD35) was determined by interpolating from the dose-response curve.
      After control measurements patients received in a randomized, double-blind
      crossover fashion either theophylline 10 mg/kg/day orally or placebo for 30 days.
      Measurements were then redone. After a washout period of 8 days the measurements
      were repeated, and patients received theophylline or placebo for a second period
      of 30 days. Measurements were again performed at the end of this last study
      period. During control all patients had normal baseline lung function data and
      showed marked bronchial hyperresponsiveness, PD35 amounting to 26 +/- 7
      micrograms of carbachol (normal value greater than 160 micrograms). No
      significant changes in PD35 were noted after placebo and washout when compared
      with control values.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1990952
TI  - Airways inflammation in nocturnal asthma.
AB  - Nocturnal asthma is a frequent problem, but the mechanism is unclear. We
      investigated the possibility that airways inflammation occurred during the night.
      Bronchoalveolar lavage fluid was analyzed in asthmatic patients with (n = 7) and
      without nocturnal asthma (n = 7) at 1600 and 0400 h. The nocturnal asthma group
      had an increase in the total leukocyte count (24.0 +/- 7.0 to 41.1 +/- 9.9 x
      10(4) cells/ml, p less than 0.05), neutrophils (1.1 +/- 0.6 to 3.7 +/- 1.5 x
      10(4) cells/ml, p less than 0.05), and eosinophils (0.5 +/- 0.1 to 1.7 +/- 0.7 x
      10(4) cells/ml, p less than 0.05) from 1600 to 0400 h. Cellular components for
      the non-nocturnal asthma group did not change. Between groups, the 1600-h cells
      were similar. At 0400 h the nocturnal asthma group had significantly higher total
      leukocyte, neutrophil, eosinophil, lymphocyte, and epithelial cell counts. For
      all subjects, the overnight fall in peak expiratory flow rates was correlated to
      the change in neutrophils (r = 0.54, p less than 0.05) and eosinophils (r = 0.77,
      p less than 0.05). We conclude that the nocturnal worsening of asthma has an
      associated cellular inflammatory response that is not seen in patients without
      overnight decrements in lung function. This inflammatory response together with
      epithelial damage may be important factors in the etiology of nocturnal asthma.

PMID- 1990953
TI  - Bronchial hyperresponsiveness in normal subjects during attenuated influenza
      virus infection.
AB  - Fourteen healthy male subjects with hemagglutination-inhibition antibody titers
      of 1:8 or less to homologous influenza A virus were studied. Six subjects
      received live, attenuated influenza virus by nasal drops and by aerosol. Although
      infection occurred in these six subjects, with the development of 4-fold or
      greater increases in hemagglutination-inhibition antibody titers, they remained
      asymptomatic. Eight subjects received placebo via the same route, and did not
      develop symptoms and showed no increase in antibody titer. Prior to
      administration of virus or placebo, histamine diphosphate aerosol increased
      airway resistance only slightly, and there was no difference between the virus
      and placebo groups. Two days after inoculation, bronchomotor responses in the
      placebo group were unchanged (p greater than 0.05), but in the virus-infected
      group, bronchomotor responses were significantly greater than in the preinfected
      state (p less than 0.01). Isoproterenol hydrochloride reversed and prevented the
      increase in airway resistance after histamine, suggesting that the
      bronchoconstriction was caused by smooth muscle contraction. Our findings
      indicate that transient, asymptomatic respiratory virus infection augments airway
      smooth muscle responses.

PMID- 1990954
TI  - Respiratory membrane permeability and bronchial hyperreactivity in patients with
      stable asthma. Effects of therapy with inhaled steroids.
AB  - In patients with stable asthma, we assayed plasma proteins in the bronchoalveolar
      lavage fluid to obtain information on plasma exudation into the airways. Fourteen
      nonsmoking patients with asthma who were in a stable period of their disease and
      eight nonsmoking healthy volunteers were studied. The ratios of the
      concentrations of albumin, ceruloplasmin (CP), and alpha-2-macroglobulin (A2M)
      between blood and epithelial lining fluid were calculated (cQalb, cQCP, and
      cQA2M). The cQalb was increased in the patients (Mann-Whitney U test, p less than
      0.05). In 10 patients the bronchial hyperreactivity was assessed with histamine
      provocation tests. Significant relationships between the cQalb, cQCP, and cQA2M
      on the one hand and PC15 on the other hand were found (Spearman's rank
      correlation: r = -0.62, p less than 0.05; r = -0.61, p less than 0.05; r = -0.79,
      p less than 0.01, respectively). Fourteen patients were treated with two
      inhalations of 200 micrograms glucocorticosteroids per day in a 3-month
      prospective study. Three of them were excluded from further study because of an
      intercurrent exacerbation of asthmatic symptoms during therapy. In the 11
      patients with stable asthma, the cQalb and cQA2M decreased after treatment with
      inhaled steroids (Wilcoxon's matched pairs signed rank test, p less than 0.03).
      Our results show that in patients with stable asthma, there is an increased
      plasma exudation into the airways, most likely caused by an increased respiratory
      membrane permeability. The plasma exudation correlated with the bronchial
      hyperreactivity to histamine, and it decreased after corticosteroid therapy.

PMID- 1990955
TI  - Effect of cooling on responses of isolated human airways to pharmacologic and
      electrical stimulation.
AB  - We studied the effect of cooling on the responses of isolated human airways to
      the beta-agonist isoproterenol, the alpha/beta-agonist norepinephrine in the
      presence of the beta-blocker timolol, methacholine, leukotriene C4 (LTC4), and
      histamine. In addition, the effect of cooling on baseline airway tone and
      responses to electric field stimulation (EFS) was studied. At 27 degrees C the
      sensitivity (-logEC50) and maximal response to isoproterenol were unchanged. No
      measurable response was found to alpha-adrenergic stimulation with norepinephrine
      + timolol either before or during cooling. At 27 degrees C and 21 degrees C the
      sensitivity and maximal contraction to methacholine and LTC4 as well as the
      contraction to a single dose of histamine were reduced. Cooling diminished
      baseline airway tone. EFS produced a rapid cholinergic contraction followed by a
      deflection below baseline and a sustained noncholinergic contractile response,
      which was substantially reduced by the LTC4/D4 receptor antagonist FPL 55712
      (11.5 microM) at all three temperatures. Cooling decreased the cholinergic
      response to EFS and increased the sensitivity to EFS-induced relaxation. In
      contrast, the sustained noncholinergic contractile response to EFS was not
      changed, suggesting that cooling facilitates the synthesis of LTC4/D4 that
      follows EFS and/or inhibits its inactivation. We conclude that in nonasthmatic,
      isolated human airways slow cooling of the airway wall down to 21 degrees C does
      not cause bronchoconstriction and does not increase the responsiveness to
      contractile or relaxing agonists. However, cooling increases the sensitivity to
      EFS-induced relaxation and might facilitate the accumulation of leukotriene C4/D4
      in the airway wall.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1990956
TI  - Lymphokine-induced airway hyperresponsiveness in the rat.
AB  - We evaluated the potential role of the lymphocyte in chronic airway inflammation
      and responsiveness by repeated administration to rats of interleukin-2 (IL-2),
      the principal lymphokine responsible for lymphocyte proliferation. Lewis rats
      (mean weight, 184 +/- 2 g) received either 120,000 units of IL-2 (n = 10) or
      vehicle (n = 7) subcutaneously twice a day for 4.5 days. Animals were
      anesthetized with urethane and intubated for measurements of pulmonary resistance
      (RL) and airway responsiveness to aerosol methacholine (MCh). Lung lavage was
      performed, the animals were exsanguinated, and the lungs were fixed in 10%
      formalin. Histologic edema and the extent of infiltration of the bronchi,
      pulmonary veins, and arteries by cells was scored blindly. IL-2 increased airway
      responsiveness to MCh; the concentrations of MCh causing a doubling of RL were
      0.14 versus 1.39 mg/ml (geometric mean) for the IL-2 and vehicle group,
      respectively (p = 0.001). IL-2 significantly increased total cellular return and
      the percentage of lymphocytes, neutrophils, and eosinophils in lavage. IL-2
      caused edema and a mixed cellular infiltration of the bronchovascular tree.
      Lymphocytes predominated around the airways and veins. A correlation (r = 0.50)
      was present between airway responsiveness and airway inflammation but not with
      edema or vascular infiltration. Release of IL-2 by lymphocytes in the airways may
      be an important mediator of airway hyperresponsiveness.

PMID- 1990957
TI  - Acute effects of interleukin-2 on lung mechanics and airway responsiveness in
      rats.
AB  - We studied the acute effects of interleukin-2 (IL-2), the principal lymphokine
      responsible for lymphocyte proliferation, on lung mechanics and airway
      responsiveness to methacholine (MCh) in rats. Lewis (n = 12) and Fisher 344 (n =
      13) rats were anesthetized and intubated, and intravenous and intra-arterial
      lines were inserted. IL-2 (750,000 U/kg) was infused intravenously over 2 to 4
      min into seven Lewis and seven Fisher rats, and vehicle alone was administered to
      five Lewis and six Fisher rats. Blood pressure, heart rate, respiratory frequency
      (f), tidal volume (VT), minute ventilation (VE), and lung resistance (RL) were
      measured before and every 5 min for 45 min after the infusion of IL-2. Lung
      compliance was measured before and 30 min after IL-2. Bronchial provocation
      testing with MCh was performed 45 min after the infusion of IL-2. Subsequently,
      the animals were exsanguinated, and the lungs were removed for histologic
      examination. Infused IL-2 did not alter heart rate or blood pressure, VT, f, VE,
      and RL increased significantly by 15 min (p less than 0.05), but they returned to
      baseline by 45 min. Lung compliance decreased significantly in both rat strains.
      IL-2 increased airway responsiveness only in Lewis rats; the concentration of MCh
      that caused a doubling of RL (EC200RL) was 0.6 mg/ml and 4.3 mg/ml (p = 0.003) in
      IL-2-treated and control rats, respectively. The airway responsiveness did not
      change significantly in Fisher rats; EC200RL was 0.13 and 0.35 mg/ml for IL-2
      treated and control rats, respectively (p = 0.09).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1990958
TI  - Complement activation is a secondary rather than a causative factor in rabbit
      pulmonary artery ischemia/reperfusion injury.
AB  - We have previously demonstrated that reperfusion of a rabbit lung in vivo after
      24 h of unilateral pulmonary artery occlusion results in edema, transient
      leukopenia, and intravascular leukocyte aggregation. We hypothesized that
      complement was activated by reperfusion and that this in turn contributed to lung
      injury. In the preliminary phase of the study, we found that ischemia followed by
      reperfusion resulted in a drop in C3 to 15 +/- 10% (mean +/- SEM) of the
      prereperfusion value as compared with no change in a group of control animals
      that had undergone an identical thoracotomy but without pulmonary artery
      occlusion and reperfusion (p less than 0.05). We then studied three groups of
      animals to determine if complement depletion with cobra venom factor (CVF) prior
      to ischemia and reperfusion would prevent the injury. Rabbits treated with CVF
      but without occlusion and reperfusion did not develop significant lung edema,
      with left and right lung wet/dry ratios of 5.32 +/- 0.11 and 5.26 +/- 0.12,
      respectively. For rabbits that were not treated with CVF but underwent ischemia
      and reperfusion, the comparable numbers were 6.15 +/- 0.36 and 5.19 +/- 0.32 (p
      less than 0.05 for right versus left). For CVF-treated rabbits that underwent
      ischemia and reperfusion, the right/left difference persisted (6.77 +/- 0.48
      versus 5.35 +/- 0.14, p less than 0.01). Immunocytochemistry documented C3
      deposition in non-CVF rabbits that underwent ischemia and reperfusion but not in
      CVF-treated rabbits. We conclude that ischemia/reperfusion of the lung results in
      complement activation, but it is not a complement-dependent injury.

PMID- 1990959
TI  - Morphometric analysis of the lung in bronchopulmonary dysplasia.
AB  - We studied lung development in children with or without bronchopulmonary
      dysplasia (BPD) using light microscopic morphometry and thick lung sections
      stained for elastic fibers. One lung was obtained at autopsy from each of eight
      patients with BPD (ages, 2 to 28 months) and six children (ages, 5 days to 51
      months) who died without lung disease. Patients with BPD demonstrated severe
      somatic growth retardation and had reduced lung volumes with abnormal lobar
      volume proportions. In the central bronchi mean volume proportion of glands and
      smooth muscle was increased in BPD. Bronchiolar density was also increased, but
      it tended to normalize with advancing age. Mean bronchiolar diameter was slightly
      smaller in BPD, and bronchiolar smooth muscle hypertrophy was a constant
      histologic feature. The most striking change, however, was noted in alveolar
      structure and development. Total alveolar number was severely decreased in
      patients with BPD compared with that in control subjects, and there was little
      evidence of compensatory alveolar development with increasing age. Lung internal
      surface area was correspondingly reduced, and mean linear intercept was
      increased. Sections stained for elastic tissue demonstrated in the patients with
      BPD a simplified acinar structure with thickened, tortuous, and irregularly
      distributed alveolar elastic fibers. We conclude that in severe, fatal BPD there
      is marked impairment of lung development with alveolar hypoplasia and reduced
      internal surface area. In addition, bronchial and bronchiolar smooth muscle
      hypertrophy and bronchial gland hyperplasia may be important contributing factors
      to airflow limitation.

PMID- 1990960
TI  - Bronchoalveolar lavage analysis in Wegener's granulomatosis. A method to study
      disease pathogenesis.
AB  - A prospective analysis of bronchoalveolar lavage (BAL) in 13 patients with
      Wegener's granulomatosis (WG), 20 disease control subjects with idiopathic
      pulmonary fibrosis (IPF), and 24 normal control subjects was conducted to (1)
      evaluate the quality of the alveolar inflammatory response associated with active
      WG; (2) determine whether antineutrophil cytoplasmic antibody (ANCA) is present
      in alveolar fluid and produced in the lungs of patients with WG; and (3)
      determine whether inhaled particles or infectious agents may play an etiologic
      role in WG. BAL in untreated active WG had a marked increase in neutrophils (mean
      = 42% of total WBC count), and usually in eosinophils (mean = 4%) compared with
      that in normal control subjects (1.6% neutrophils, 0% eosinophils), and untreated
      WG in remission (5.9% neutrophils, 0% eosinophils). Disease control subjects with
      IPF, a process known to be associated with neutrophilic alveolitis, had an
      increased population of neutrophils (15.4%) and eosinophils (2.7%) in BAL.
      Leukocyte remnants, as well as intact leukocytes, could be identified within BAL
      macrophages in the patients with WG and IPF, and rarely in the normal control
      subjects. Normal subjects and control patients with IPF were all negative for
      ANCA in serum, whereas ANCA was found in serum and BAL in all patients with
      active WG who had generalized disease. Protein analysis of BAL revealed a
      disproportionate increase in the IgG to albumin ration compared with serum values
      (IgG index) in patients with active untreated disease. The increase in the IgG
      index suggests that IgG with ANCA reactivity is produced by pulmonary lymphoid
      tissue. An infectious agent in BAL was not identified by any of the techniques
      applied in this study.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1990962
TI  - Eosinophilic airway inflammation during exacerbation of asthma and its treatment
      with inhaled corticosteroid.
AB  - We have compared the inflammatory changes in the bronchial mucosa and the
      increase in the airway hyperresponsiveness in an asthmatic patient during the
      deterioration of symptoms. A striking increase in the number of bronchial
      epithelial eosinophils was associated with an increase in both airway
      hyperresponsiveness and asthma symptoms. During 16 wk of treatment with the
      inhaled corticosteroid, budesonide, the patient's clinical status and airway
      hyperresponsiveness improved. This was accompanied by an improvement in the
      ultrastructure of bronchial mucosa and a decrease in the number of epithelial
      eosinophils.

PMID- 1990961
TI  - Cellular and molecular basis of the asbestos-related diseases.
AB  - Asbestosis is an inflammatory and fibrotic process of the alveolar structures
      mediated, at least in part, by cytokines released by "activated" alveolar
      macrophages. The process of phagocytosis and "activation" of alveolar macrophages
      is poorly understood. Are all macrophages activated or only subpopulations? Which
      cytokines are up-regulated? How does the local milieu modulate profibrotic and
      antifibrotic mediators? Is protein release accompanied by up-regulation of gene
      transcription? Is there an ordered sequence of cytokine activity? What roles do
      neutrophils and lymphocytes play? How can disease progression best be quantified
      absent further exposure? Answers to these questions are important to direct
      rational strategies at interdicting the fibrotic process. The question of cancer
      and asbestos is more vexing. The processes of inflammation, fibrosis, and
      carcinogenesis appear to be closely intertwined. For example, proto-oncogenes
      such as c-sis (PDGF B-chain) are up-regulated in activated alveolar macrophages
      from fibrotic lungs; these and possibly others may play an important role in
      asbestos carcinogenesis. Second, asbestos can transfect DNA into cells.
      Furthermore, DNA can adhere to asbestos fibers, and these fibers are capable of
      direct transmigration into cells. The questions of the mechanisms of cigarette
      smoke cocarcinogenicity and latency remain. Lastly, if the bronchial epithelium
      is highly metaplastic throughout from cigarette smoking, what triggers a single
      (or several) nidus of cells to transform into carcinoma? Malignant mesothelioma
      poses the most challenging questions because of association with brief asbestos
      exposure by history. Mesothelial cells are susceptible to minute environmental
      manipulations, and changes occur after exposure to all fiber types. Yet
      epidemiologic studies point toward long amphiboles as having greater mesothelioma
      risk. To test this hypothesis, experimental data must be generated
      differentiating tumorigenesis risk from short, chrysotile fibers that can migrate
      to the parietal pleura from the associations of long amphiboles persisting in
      lung tissue. Despite the future decreasing numbers of clinical cases of asbestos
      related disease, solving the important mechanistic questions remaining will
      contribute significantly to our understanding of fibrosis and cancer.

PMID- 1990963
TI  - Aggressive cavitary pulmonary sarcoidosis.
AB  - Pulmonary sarcoidosis in a young patient is usually a relatively benign disease
      that either resolves spontaneously or remains quiescent for many years. Very
      rarely it pursues a more aggressive course leading to progressive lung
      destruction. We report a young patient who presented with Stage III sarcoidosis
      and over a period of 4 yr progressed to severe cavitary disease with frequent
      superinfections leading to bronchiectasis and chronic suppuration of the lung,
      eventually requiring a pneumonectomy.

PMID- 1990964
TI  - Hypersensitivity pneumonitis versus invasive pulmonary aspergillosis: two cases
      with unusual pathologic findings and review of the literature.
AB  - Two brothers simultaneously exposed to moldy hay, who developed differing forms
      of Aspergillus-related lung disease, are presented. Patient 1 developed a true
      case of hypersensitivity lung disease, whereas his brother developed invasive
      aspergillosis with bronchoalveolar lavage eosinophilia and unusual pathologic
      features including tissue eosinophilia. The possible overlap between
      hypersensitivity pneumonitis and invasive aspergillosis in the immunocompetent
      host is discussed.

PMID- 1990965
TI  - Abnormalities in airway smooth muscle in fatal asthma. A comparison between
      trachea and bronchus.
AB  - Tracheal smooth muscle from seven cases of fatal asthma demonstrated an increased
      contractile response to histamine, acetylcholine, and electrical stimulation of
      intrinsic cholinergic nerves; impaired relaxation to isoproterenol, and possibly
      theophylline, was also evident (1). Fourth generation bronchial spirals from the
      same patients were also studied, and these results were compared with those of
      the trachea and normal bronchi (n = 5). In contrast to trachea, contractile
      responses in asthmatic bronchi to acetylcholine, histamine, and cholinergic nerve
      stimulation were similar to those in control bronchi. The potency of isoprenaline
      (IC50) was reduced 9.4-fold (p less than 0.003), similar to trachea (4.5-fold),
      whereas theophylline responses were normal. The discrepant results obtained may
      reflect differences in the disease process, including rates of postmortem change,
      at the two anatomic sites.

PMID- 1990966
TI  - Isolation of Coccidioides immitis from bronchoalveolar lavage is diagnostic of
      infection.

PMID- 1990967
TI  - Kinetic characterization of branched chain ketoacid dehydrogenase.
AB  - Initial velocity and product inhibition experiments were performed to
      characterize the kinetic mechanism of branched chain ketoacid dehydrogenase (the
      branched chain complex) activity. The results were directly compared to predicted
      patterns for a three-site ping-pong mechanism. Product inhibition experiments
      confirmed that NADH is competitive versus NAD+ and isovaleryl CoA is competitive
      versus CoA. Furthermore, both NADH and isovaleryl CoA were uncompetitive versus
      ketoisovaleric acid. These results are consistent with a ping-pong mechanism and
      are similar to pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase.
      However, inhibition patterns for isovaleryl CoA versus NAD+ and NADH versus CoA
      are not consistent with a ping-pong mechanism. These patterns may result from a
      steric interaction between the flavoprotein and transacetylase subunits of the
      complex. To determine the kinetic mechanism of the substrates and feedback
      inhibitors (NADH and isovaleryl CoA) of the branched chain complex, it was
      necessary to define the interaction of the inhibitors at nonsaturating fixed
      substrate (CoA and NAD+) concentrations. While the competitive inhibition
      patterns were maintained, slope replots for NADH versus NAD+ at nonsaturating CoA
      concentrations were parabolic. This unexpected finding resembles a linear mixed
      type of inhibition where the inhibition is a combination of pure competitive and
      noncompetitive inhibition.

PMID- 1990969
TI  - The secondary structure of two recombinant human growth factors, platelet-derived
      growth factor and basic fibroblast growth factor, as determined by Fourier
      transform infrared spectroscopy.
AB  - The secondary structures of two recombinant human growth factors, platelet
      derived growth factor and the basic fibroblast growth factor, have been
      quantitatively examined by using Fourier transform infrared spectroscopy. These
      studies, carried out in D2O, focus on the conformation-sensitive amide I region.
      Resolution enhancement techniques, including Fourier self-deconvolution and
      derivative spectroscopy, were combined with band fitting techniques to quantitate
      the spectral information from the broad, overlapped amide I band. The results
      presented here indicate that both proteins are rich in beta-structures. The
      remainder of the platelet-derived growth factor exists largely as irregular or
      disordered conformations with a moderate amount of alpha-helix and a small
      portion of reverse turns. By contrast, the basic fibroblast growth factor is much
      richer in reverse turn structures and contains a lesser portion of irregularly
      folded or disordered structures. Based on circular dichroism studies which
      indicate no alpha-helix in bFGF, components near 1655 cm-1 in the bFGF spectra
      are tentatively assigned to loops. The results of this study emphasize the need
      for using a combination of circular dichroism and infrared studies for
      spectroscopic characterization of protein secondary structure.

PMID- 1990968
TI  - Retinoylation of proteins in leukemia, embryonal carcinoma, and normal kidney
      cell lines: differences associated with differential responses to retinoic acid.
AB  - In HL60 cells a nuclear protein of Mr 55,000 is retinoylated, with the formation
      of a thioester bond. To gain further knowledge on the role of retinoylation we
      studied it in cell lines with varied responses to retinoic acid (RA). Compared to
      HL60 the extent of retinoylation (mol/cell) was about fivefold higher in
      HL60/MRI, a mutant which is more sensitive to RA than HL60. Retinoylation
      occurred to the same extent and at similar rates in HL60 and in HL60/RA-res, a
      mutant resistant to differentiation by RA. One-dimensional polyacrylamide gel
      electrophoresis patterns for the three HL60 cell lines were similar. However, two
      dimensional polyacrylamide gel electrophoresis patterns of the three HL60 cell
      lines were distinct. While we saw the same major retinoylated protein of Mr
      55,000 in the three cell lines, the HL60/RA-res cells also contained a high level
      of a protein with the same Mr and a lower pI. The extent of retinoylation was
      greater in the RA-sensitive embryonal carcinoma cell line, PCC4.aza1R, than in a
      RA-resistant cell line, PCC4.(RA)-2. One-dimensional polyacrylamide gel
      electrophoresis patterns of retinoylated proteins of the embryonal carcinoma cell
      lines were different from HL60 and from each other. The retinoylation pattern of
      the normal canine kidney cell line (MDCK) was different from either HL60 or the
      embryonal carcinoma cells. These results showed the retinoylation was widespread
      and that the response to RA of different cell types may depend on the
      retinoylation of specific proteins.

PMID- 1990970
TI  - Physicochemical characterization of bovine retinal arrestin.
AB  - The native conformation of bovine retinal arrestin has been characterized by a
      variety of spectroscopic methods. The purified protein gives rise to a near uv
      absorption band centered at 279 nm which results from the absorbance of its 14
      tyrosine and one tryptophan residue. The extinction coefficient for this
      absorption band was determined to be 38.64 mM-1, cm-1 using the tyrosinate
      tyrosine difference spectrum method; this extinction coefficient is ca. 17% lower
      than the previously reported value, and provides estimates of protein
      concentration which are in good agreement with estimates from the Bradford
      colorimetric assay. When native arrestin is purified to homogeneity, it displays
      a fluorescence spectrum which is dominated by tyrosine emission with no
      discernible contribution from tryptophan. Observation of the tyrosine-like
      fluorescence is dependent on the purity and structural integrity of the protein.
      Denaturation of arrestin by guanidine hydrochloride results in a diminution of
      tyrosine fluorescence and the concomitant appearance of a second fluorescence
      maximum at ca. 340 nm, presumably due to the single tryptophan residue. Thermal
      denaturation of arrestin leads to a conformation characterized by a broad
      fluorescence band centered at ca. 325 nm. Study of the arrestin fluorescence
      spectrum as a function of temperature indicates that the thermal denaturation is
      well modeled as a two-state transition with a transition midpoint of 60 degrees
      C. Temperature-dependent far uv circular dichroism studies indicate that changes
      in secondary structure occur coincident with the change in fluorescence. Studies
      of the temperature dependence of arrestin binding to light-adapted phosphorylated
      rhodopsin shows a strong correlation between the fluorescence spectral features
      of arrestin and its ability to bind rhodopsin. These data suggest that the
      relative intensities of tyrosine and tryptophan fluorescence are sensitive to the
      structural integrity of the native (i.e., rhodopsin binding) state of arrestin,
      and can thus serve as useful markers of conformational transitions of this
      protein. The lack of tryptophan fluorescence for native arrestin suggests an
      unusual environment for this residue. Possible mechanisms for this tryptophan
      fluorescence quenching are discussed.

PMID- 1990971
TI  - zeta-Crystallin is a major protein in the lens of Camelus dromedarius.
AB  - Camel (Camelus dromedarius) lenses contain a protein with an apparent subunit Mr
      38,000 that constitutes approximately 8-13% of the total protein. The protein has
      been purified and has a native Mr 140,000 as determined by gel filtration. This
      is consistent with its being a tetramer. The protein reacts with antibodies
      raised against both guinea pig zeta-crystallin and peptides corresponding to
      amino acids 1-10 and 295-308, but not to antibodies raised against amino acids
      320-328 of zeta-crystallin. Based on these criteria it is concluded that this
      protein, which is a major constituent of camel lens, is zeta-crystallin. This may
      be the first example of a protein (enzyme) being independently utilized as a
      crystallin in the lens of species from two mammalian orders.

PMID- 1990972
TI  - Effects of sulfate deprivation on the production of chondroitin/dermatan sulfate
      by cultures of skin fibroblasts from normal and diabetic individuals.
AB  - Human skin fibroblast monolayer cultures from two normal men, three Type I
      diabetic men, and one Type I diabetic woman were incubated with [3H]glucosamine
      in the presence of diminished concentrations of sulfate. Although total synthesis
      of [3H]chondroitin/dermatan glycosaminoglycans varied somewhat between cell
      lines, glycosaminoglycan production was not affected within any line when sulfate
      levels were decreased from 0.3 mM to 0.06 mM to 0.01 mM to 0 added sulfate.
      Lowering of sulfate concentrations resulted in diminished sulfation of
      chondroitin/dermatan in a progressive manner, so that overall sulfation dropped
      to as low as 19% for one of the lines. Sulfation of chondroitin to form
      chondroitin 4-sulfate and chondroitin 6-sulfate was progressively and equally
      affected by decreasing the sulfate concentration in the culture medium. However,
      sulfation to form dermatan sulfate was preserved to a greater degree, so that the
      relative proportion of dermatan sulfate to chondroitin sulfate increased.
      Essentially all the nonsulfated residues were susceptible to chondroitin AC
      lyase, indicating that little epimerization of glucuronic acid residues to
      iduronic acid had occurred in the absence of sulfation. These results confirm the
      previously described dependency of glucuronic/iduronic epimerization on
      sulfation, and indicate that sulfation of the iduronic acid-containing
      disaccharide residues of dermatan can take place with sulfate concentrations
      lower than those needed for 6-sulfation and 4-sulfation of the glucuronic acid
      containing disaccharide residues of chondroitin. There were considerable
      differences among the six fibroblast lines in susceptibility to low sulfate
      medium and in the proportion of chondroitin 6-sulfate, chondroitin 4-sulfate, and
      dermatan sulfate. However, there was no pattern of differences between normals
      and diabetics.

PMID- 1990973
TI  - Conformational stability of the covalent complex between elastase and alpha 1
      proteinase inhibitor.
AB  - The equilibrium unfolding-refolding process of the elastase-alpha 1-proteinase
      inhibitor complex, induced by guanidinium chloride, was followed by spectroscopic
      methods. A reversible transition with a midpoint at 2.04 +/- 0.04 M guanidinium
      chloride was observed by fluorescence. This transition was attributed to elastase
      on the basis of circular dichroism and uv absorption difference data obtained for
      the covalent complex and for the free proteins. The conformational stability of
      elastase in the complex was analyzed considering the approximation of a two-state
      transition. The free energy of denaturation delta GH2O was 4.2 kcal.mol-1 for
      complexed elastase compared to 10.5 kcal.mol-1 for the free enzyme. Such a
      decrease in the stability of elastase suggests that, after forming the covalent
      complex with the inhibitor, the enzyme undergoes not only the expected local
      modifications of the active site, but also an extensive structural
      reorganization.

PMID- 1990974
TI  - Degradation of erythrocyte glycophorin results in increased membrane bound
      hemoglobin.
AB  - Degradation of glycophorin by trypsin in intact red cells results in an increase
      in hemoglobin bound to the membrane. Incubation of resealed ghosts made from
      these cells demonstrated that the hemoglobin was bound to the intracellular
      membrane surface. We found that treatment of hemoglobin with KCNO inhibited the
      ability of hemoglobin to bind to the membrane. Addition of KCNO to intact cells
      followed by trypsin treatment abolished the additional membrane-bound hemoglobin,
      indicating that the bound hemoglobin resulted from increased Band 3 binding.
      Treatment of intact cells with neuraminidase also resulted in increased membrane
      bound Hb, which correlated with the amount of sialic acid released. Scatchard
      analysis revealed that enzyme treatment increased the affinity of hemoglobin for
      the high affinity Band 3 binding site, while KCNO treatment abolished this
      binding. Taken together, these studies demonstrate that extracellular proteolytic
      degradation of glycophorin by proteases similar to those released by cells of the
      reticuloendothelial system results in an increased ability of hemoglobin to bind
      to Band 3.

PMID- 1990975
TI  - Effect of parathyroid hormone on rat renal cAMP-dependent protein kinase and
      protein kinase C activity measured using synthetic peptide substrates.
AB  - The actions of parathyroid hormone (PTH) on the renal cortex are thought to be
      mediated primarily by cAMP-dependent protein kinase (PKA) with some suggestion of
      a role for protein kinase C (PKC). However, present methods for assaying PKA and
      PKC in subcellular fractions are insensitive and require large amounts of
      protein. Recently, a sensitive method for measuring the activity of protein
      kinases has been reported. This method uses synthetic peptides as substrates and
      a tandem chromatographic procedure for isolating the phosphorylated peptides. We
      have adapted this method to study the effect of PTH on PKA and PKC activity using
      thin slices of rat renal cortex. PTH (250 nM) stimulated cytosolic PKA activity
      four- to fivefold within 30 s, and PKA activity was sustained for at least 5 min.
      PTH also rapidly stimulated PKC activity in the membrane fraction and decreased
      PKC activity in the cytosol. These changes were maximal at 30 s, but unlike
      changes in PKA, they declined rapidly thereafter. PTH significantly activated PKC
      only at concentrations of 10 nM or greater. This study demonstrates that PTH does
      activate PKC in renal tissue, although the duration of activation is much less
      than for PKA. It also demonstrates that a combination of synthetic peptides with
      tandem chromatography can be used as a sensitive assay procedure for protein
      kinase activity in biological samples.

PMID- 1990976
TI  - Propionyl-CoA condensing enzyme from Ascaris muscle mitochondria. I. Isolation
      and characterization of multiple forms.
AB  - The condensation of two propionyl-CoA units or a propionyl-CoA with acetyl-CoA is
      required for the synthesis of 2-methylvalerate or 2-methylbutyrate, respectively,
      two of the major fermentation products of Ascaris anaerobic muscle metabolism. An
      enzyme that preferentially catalyzes the condensation of propionyl-CoA rather
      than acetyl-CoA has been purified from the mitochondria of the parasitic
      intestinal nematode Ascaris lumbricoides var. suum. The purified enzyme is over
      10 times more active with propionyl-CoA than with acetyl-CoA as substrate. It
      also catalyzes the coenzyme A-dependent hydrolysis of acetoacetyl-CoA at a rate
      four times higher than the propionyl-CoA condensation reaction. The purified
      Ascaris condensing enzyme preferentially forms the 2-methyl-branched-chain keto
      acids rather than the corresponding straight chain compounds. The native
      molecular weight of the purified enzyme was estimated to be 160,000 by gel
      filtration chromatography and 158,000 by high pressure liquid chromatography. The
      enzyme migrated as a single protein band with Mr 40,000 during sodium dodecyl
      sulfate-polyacrylamide electrophoresis, indicating that the enzyme is composed of
      four subunits of the same molecular weight. Chromatography on CM-sephadex
      resulted in the isolation of two separate peaks of activity, designated as A and
      B. Both A and B had the same molecular weight and subunit composition. However,
      they differed in their specific activities and isoelectric points. The pIs of
      condensing enzymes A and B were 7.6 and 8.4, respectively. Propionyl-CoA was the
      best substrate for the condensation reaction with both enzymes. However, the
      specific activity of enzyme B for both propionyl-CoA condensation (3.4
      mumol/min/mg protein) and acetoacetyl-CoA thiolysis (13.8 mumol/min/mg protein)
      was 2.4 times higher than that obtained with enzyme A. Similarly, chromatography
      on phosphocellulose resolved the Ascaris condensing enzyme activity into one
      minor and two major peaks. All of these components had the same molecular weight
      and subunit composition, but differed in their specific activities. The two major
      phosphocellulose peaks cross-reacted immunologically when examined by the
      Ouchterlony double immunodiffusion technique. In addition, antiserum against the
      phosphocellulose most active form cross-reacted with forms A and B isolated by
      chromatography of the enzyme on CM-Sephadex, indicating that all forms were
      immunochemically related.

PMID- 1990977
TI  - Recombinant rat guanidinoacetate methyltransferase: structure and function of the
      NH2-terminal region as deduced by limited proteolysis.
AB  - Recombinant rat liver guanidinoacetate methyltransferase, a monomeric protein
      with Mr 26,000, is inactivated upon incubation with low concentrations of
      trypsin. Examination of the reaction products by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and high-performance liquid chromatography
      followed by amino acid analysis and sequencing of isolated peptides reveals that
      the inactivation is due to the cleavage of the NH2-terminal segment after Arg20.
      The cleaved peptide is not tightly associated with the rest of the protein. The
      rate of inactivation is not affected by the presence of either S
      adenosylmethionine (AdoMet) or guanidinoacetate, but a substantial retardation of
      inactivation is observed when both substrates are present. The cleavage at Arg20
      is also slowed by cross-linking Cys15 and Cys90 by a disulfide bond. An
      equilibrium binding study shows that guanidinoacetate methyltransferase in the
      free form binds AdoMet but not guanidinoacetate. The trypsin-modified enzyme,
      despite having no catalytic activity, can weakly bind AdoMet and guanidinoacetate
      in the presence of AdoMet. Chymotrypsin rapidly hydrolyzes the peptide bond after
      Trp19, and elastase cleaves the bond after Ala24, leading in both cases to loss
      of activity. The results obtained in this study suggest that the portion of the
      methyltransferase around residues 19-24 is highly exposed to the solvent and
      flexible. The results also indicate that the NH2-terminal region is not directly
      involved in substrate binding but plays a role in catalysis.

PMID- 1990978
TI  - The toxicity of menadione (2-methyl-1,4-naphthoquinone) and two thioether
      conjugates studied with isolated renal epithelial cells.
AB  - Menadione (2-methyl-1,4-naphthoquinone) was used as a model compound to test the
      hypothesis that thioether conjugates of quinones can be toxic to tissues
      associated with their elimination through a mechanism involving oxidative stress.
      Unlike menadione, the glutathione (2-methyl-3-(glutathion-S-yl)-1,4
      naphthoquinone; MGNQ) and N-acetyl-L-cysteine (2-methyl-3-(N-acetylcysteine-S-yl)
      1,4-naphthoquinone; M(NAC)NQ) thioether conjugates were not able to arylate
      protein thiols but were still able to redox cycle with cytochrome c
      reductase/NADH and rat kidney microsomes and mitochondria. Interestingly,
      menadione and M(NAC)NQ were equally toxic to isolated rat renal epithelial cells
      (IREC) while MGNQ was nontoxic. The toxicity of both menadione and M(NAC)NQ was
      preceded by a rapid depletion of soluble thiols and was associated with a
      depletion of soluble thiols and was associated with a depletion of protein
      thiols. Treatment of IREC with the glutathione reductase inhibitor, 1,3-bis(2
      chloroethyl)-1-nitrosourea, potentiated the thiol depletion and toxicity observed
      with menadione and M(NAC)NQ indicating the involvement of oxidative stress in
      this model of renal cell toxicity. The lack of MGNQ toxicity can be attributed to
      an intramolecular cyclization reaction which destroys the quinone nucleus and
      therefore eliminates its ability to redox cycle. These findings have important
      implications with regard to our understanding of the toxic potential of quinone
      thioether conjugates and of quinone toxicity in general.

PMID- 1990979
TI  - Purification and characterization of recombinant antistasin: a leech-derived
      inhibitor of coagulation factor Xa.
AB  - Antistasin (ATS) is a selective, tight-binding inhibitor of blood coagulation
      Factor Xa originally isolated from the salivary glands of the Mexican leech
      Haementeria officinalis. In order to provide sufficient quantities of ATS to
      further investigate the role of Factor Xa in blood coagulation, a recombinant
      version of ATS has been produced in an insect baculovirus host-vector system. In
      this study, we describe the purification and in vitro and in vivo
      characterization of a single recombinant antistasin (rATS) isoform. The purified
      protein constitutes a minor isoform relative to the more abundant ATS isoforms
      present in leech salivary gland extracts. In vitro, rATS inhibits purified human
      Factor Xa stoichiometrically, prolongs plasma-based clotting assays at nanomolar
      concentrations, and like native ATS, is cleaved at a single position by Factor Xa
      during the course of inhibition. An initial evaluation of the in vivo efficacy of
      rATS was addressed utilizing a rhesus monkey model of mild disseminated
      intravascular coagulation. rATS was shown to fully suppress thromboplastin
      induced fibrinopeptide A generation in a dose-dependent fashion. The availability
      of rATS should provide a valuable tool for the critical evaluation of the
      specific role played by Factor Xa in coagulation.

PMID- 1990980
TI  - Modification of hepatic vitamin E stores in vivo. I. Alterations in plasma and
      liver vitamin E content by methyl ethyl ketone peroxide.
AB  - Since experiments with freshly isolated rat hepatocytes have shown that cellular
      vitamin E is consumed in response to insult by compounds that induce an oxidative
      stress only after cellular glutathione (GSH) concentrations have been
      substantially depleted, experiments were performed to determine whether this
      sequence of events occurred in response to oxidative insult in vivo. The role
      that plasma vitamin E plays in the response to chemically induced oxidative
      injury in vivo was also assessed. Treatments with 40 mg/kg of methyl ethyl ketone
      peroxide (MEKP) quickly induced lipid peroxidation in vivo and from one to 4 h
      after treatment caused a depression in the plasma content of vitamin E and the
      liver content of GSH, as well as signs of toxicity (elevations in serum
      activities of alanine and aspartate aminotransferases). At these time points
      however, the liver content of vitamin E was either indistinguishable from or
      slightly elevated from controls. By 12 to 24 h after treatment the liver content
      of vitamin E was reduced by 20-25% whereas values for all other indicators had
      returned toward control levels. Pretreatment of rats with L-buthionine-S,R
      sulfoximine, an inhibitor of GSH by 4 or 24 h after treatment, did not alter the
      time course or extent of hepatic vitamin E depletion that was observed after
      treatment with MEKP. Other compounds that induce oxidative stress and lipid
      peroxidation to the liver, carbon tetrachloride and menadione, did not provoke an
      alteration in hepatic vitamin E levels as compared to controls 1 day after
      treatment. These findings indicate that depletion of hepatic vitamin E may not
      occur as an immediate consequence of oxidative insult to the liver and that the
      depletion of hepatic vitamin E levels may not be related to the extent of prior
      GSH depletion. Moreover, these findings suggest that alterations in the plasma
      concentration of vitamin E may not reflect concurrent alterations in hepatic
      vitamin E levels. A mechanism whereby liver vitamin E stores are mobilized for
      the maintenance of plasma vitamin E levels is proposed.

PMID- 1990981
TI  - Characterization of a H+/NO3- symport associated with plasma membrane vesicles of
      maize roots using 36ClO3- as a radiotracer analog.
AB  - The mechanism of NO3- transport was examined in isolated plasma membrane vesicles
      from maize (Zea mays L., hybrid B73 X LH 51) roots using 36ClO3- as a radiotracer
      analog for NO3-. When an acid-exterior delta pH was imposed across the vesicle
      membrane, uptake of 36ClO3- was stimulated and the time course of radiolabel
      uptake displayed an overshoot phenomenon characteristic of the coupling of one
      solute gradient ot the movement of another solute. Evidence supporting delta pH
      as the driving force for 36ClO3- uptake included a dependence of the overshoot
      peak and initial rate of 36ClO3- uptake on the magnitude of the imposed delta pH,
      the occurrence of delta pH-driven 36ClO3- uptake in the presence of
      KSCN/valinomycin, and the ability of an imposed delta pH to drive 36ClO3- uptake
      when radiolabel was equilibrated across the membrane. When delta pH-driven 36ClO3
      transport was examined in the presence of NO3-, radiolabel uptake was inhibited
      in a competitive manner. This was consistent with the carrier having the capacity
      to use either ClO3- or NO3- and supports the use of this radiotracer as an analog
      for NO3- in transport studies. When delta pH-driven 36ClO3- uptake was examined
      as a function of 36ClO3- concentration and delta pH, saturation kinetics were
      observed and the magnitude of the imposed delta pH affected the Km but not the
      Vmax for 36ClO3- uptake. This suggested an ordered binding mechanism where 36ClO3
      would bind to the protonated form of the carrier prior to translocation.
      Radiolabeled 36ClO3- uptake was inhibited by treatment of the vesicles with
      phenylglyoxal, suggesting the involvement of arginine moieties in the process of
      transport. Taken together, these results support the presence of a H+/NO3-
      symport carrier at the plasma membrane which could be involved in mediating
      energy-dependent NO3- uptake into plant cells.

PMID- 1990982
TI  - Persistent Candida intertrigo treated with fluconazole.

PMID- 1990983
TI  - Urticaria pigmentosa. Systemic evaluation and successful treatment with topical
      steroids.
AB  - Nine patients with adult-onset urticaria pigmentosa were studied for the
      incidence of extracutaneous mast cell involvement and the efficacy of potent
      topical corticosteroid therapy for cutaneous lesions. Seven of the nine patients
      had increased mast cells in the marrow biopsy specimens, and five patients had
      focal aggregates of mast cells. The bone scan was abnormal in one patient. Liver
      spleen scans revealed a shift of colloid uptake from liver to spleen in four
      patients. No abnormal gastrointestinal tract roentgenograms were obtained.
      Urinary histamine metabolites correlated with nodular bone marrow involvement,
      but not with other parameters. Results of the psychoneurologic testing revealed
      significant deviation from the norm with a verbal memory deficit in all nine
      patients and abnormalities on the Minnesota Multiphasic Personality Inventory in
      four patients. All nine patients were treated with 0.05% betamethasone
      dipropionate ointment under occlusion over half of the body nightly for 6 weeks.
      Seven of nine patients treated responded with almost complete resolution of their
      lesions. Hypothalamic pituitary adrenal axis suppression was evaluated with
      intramuscular cosyntropin stimulation and metyrapone administration during
      treatment. Only two patients, both of whom used the medication improperly,
      developed transient abnormalities. Slow return of lesions was noted 6 months
      after completion of therapy. Remissions could be lengthened with single weekly
      applications of topical steroids. Systemic involvement is frequent in patients
      with cutaneous mast cell disease and it is best demonstrated by bone marrow
      biopsy. Mast cell lesions can be safely and effectively treated with topical
      steroids in motivated patients.

PMID- 1990984
TI  - A double-blind controlled comparison of generic and trade-name topical steroids
      using the vasoconstriction assay.
AB  - Six generic formulations of five topical steroids were compared for
      bioequivalence with their trade-name counterparts using an in vivo
      vasoconstriction assay. Two of six generic formulations were found to show
      significantly less vasoconstriction than the respective trade-name topical
      steroids. The issue of generic equivalence of topical steroids is discussed, with
      particular emphasis on the vagaries of the vasoconstriction assay.

PMID- 1990985
TI  - Capillary hemangiomas and treatment with the flash lamp-pumped pulsed dye laser.
AB  - Strawberry, or capillary, hemangiomas are common vascular neoplasms, with an
      incidence of approximately 2.6% in neonates. They usually develop in the first
      few weeks of life, so that between 1 month and 1 year the incidence rises to
      between 8.7% and 10.1%. These lesions may grow quite large in the first year of
      life, and they may ulcerate or obstruct a vital organ or function. The great
      majority will spontaneously regress after the first year of life. Parents are
      often alarmed at the sight of these hemangiomas and need reassurance that the
      great majority will regress spontaneously. Treatments such as cryosurgery,
      irradiation, radium instillation, corticosteroid therapy, or surgical excision
      are often ineffective or cause significant morbidity. We describe 10 children
      with capillary hemangiomas treated with the flash lamp-pumped pulsed dye laser.
      The patients ranged in age from 7 weeks to 5.5 years at the beginning of laser
      therapy. The patients underwent 3.1 +/- 1 (mean +/- SD) laser treatments, with a
      mean regression of the lesions of 69.9% +/- 4.5%. All patients demonstrated some
      diminution in the size and color of their hemangiomas after the treatments, and
      there were no ill effects, such as ulceration, hemorrhage, infection, or
      scarring. There was no evidence of hyperpigmentation or hypopigmentation. Pulsed
      dye laser therapy should be considered as an option in the treatment of capillary
      hemangiomas, preferably prior to their full evolution. It is also a useful
      therapeutic approach in those hemangiomas that are slow to regress in older
      children.

PMID- 1990986
TI  - Eosinophilic fasciitis associated with tryptophan ingestion. A manifestation of
      eosinophilia-myalgia syndrome.
AB  - Recently, the ingestion of tryptophan has been associated with eosinophilia
      myalgia syndrome, which is characterized by eosinophilia, myalgias, and several
      less consistently reported findings. We treated 13 patients who exhibited
      clinical features of eosinophilic fasciitis who were taking high-dose tryptophan
      before the onset of clinical symptoms. Twelve patients exhibited eosinophilia,
      with eosinophil counts ranging from 0.13 to 0.88. The remaining patient was
      taking oral corticosteroids when her eosinophil count was determined. Eight
      patients complained of myalgias. Other symptoms included arthralgias, pruritus,
      cutaneous burning, weakness, fever, rashes, malaise, edema, muscle spasms, and
      alopecia. 5-Hydroxyindoleacetic acid levels were elevated in four of the eight
      urine specimens that were tested. Our findings suggest that previously diagnosed
      cases of eosinophilic fasciitis may represent variants of tryptophan-associated
      eosinophilia-myalgia syndrome. Derangements in the metabolism of tryptophan may
      play a role in sclerotic diseases.

PMID- 1990987
TI  - Intercellular IgA dermatosis of childhood. Selective deposition of monomer IgA1
      in the intercellular space of the epidermis.
AB  - We describe a 7-year-old girl with recurrent pruritic vesiculopustular lesions
      involving the trunk, extremities, face, and oral mucosa. Histopathologic
      examination revealed intraepidermal bullae containing neutrophils and
      eosinophils, and direct immunofluorescence test showed the deposition of IgA in
      the intercellular space of the epidermis. Circulating IgA anti-intercellular
      antibodies were also detected by indirect immunofluorescence test.
      Immunofluorescence studies using monoclonal antibodies to human IgA subclasses
      showed that these IgA antibodies belonged to IgA1. Antisera against J chain and
      secretory component did not show any specific intercellular staining. Surface
      IgA(+)-B cells were transiently increased in the peripheral blood during the
      active stage of the disease. These results indicated the extragut origin of these
      IgA antibodies. Dapsone therapy was shown to be very effective.

PMID- 1990988
TI  - Ichthyosis, exocrine pancreatic insufficiency, impaired neutrophil chemotaxis,
      growth retardation, and metaphyseal dysplasia (Shwachman syndrome). Report of a
      case with extensive skin lesions (clinical, histological, and ultrastructural
      findings)
AB  - The Shwachman syndrome comprises exocrine pancreatic insufficiency, growth
      retardation, and bone marrow hypoplasia resulting in neutropenia. Clinical,
      morphological, and ultrastructural studies, as well as hair analysis, were
      performed in a patient with Shwachman's syndrome and severe ichthyosis. Clinical
      findings were lamellar ichthyosiform desquamation on the extremities. The hair
      was scanty and short on the scalp, in the eyelashes, and in the eyebrows. The
      nails were hyperkeratotic. Morphologic findings were slight, regular acanthosis
      and severe diffuse hyperkeratosis with variable parakeratosis. The granular layer
      was thickened. The papillary dermis showed very slight perivascular lymphocyte
      infiltration. The most prominent ultrastructural finding was the presence of
      solitary or multiple droplets of varying size in the cytoplasm of the
      keratinocytes. Hair analysis revealed no abnormalities; the cystine concentration
      in hair specimens was normal.

PMID- 1990989
TI  - Corticosteroid-induced juxta-articular adiposis dolorosa.
AB  - Long-term treatment with high doses of corticosteroids leads to the development
      of truncal obesity and focal fatty deposition. These deposits characteristically
      are located on the face, the nuchal and truncal areas, and episternally, as well
      as in the mediastinum and epicardium. We studied a patient with juxta-articular
      adiposis dolorosa who had L-tryptophan-associated eosinophilia-myalgia syndrome
      and was treated with high doses of prednisone. This is the first reported case of
      adiposis dolorosa occurring as a complication of corticosteroid treatment.
      Alterations of fat metabolism induced by corticosteroid excess may have played a
      role in the development of this unusual painful syndrome.

PMID- 1990991
TI  - A plea for a biologic approach to hemangiomas of infancy.

PMID- 1990990
TI  - The challenge of limiting the spread of human immunodeficiency virus by
      controlling other sexually transmitted diseases.

PMID- 1990992
TI  - Exuberant tumoral lesions on the dorsum of the foot. Pretibial myxedema.

PMID- 1990993
TI  - Blistering eruption in a diabetic. Bullosis diabeticorum.

PMID- 1990994
TI  - Acral necrosis in a patient with chronic renal failure. Calciphylaxis.

PMID- 1990995
TI  - Tender nodules on the legs. Subcutaneous fat necrosis; associated pancreatitis.

PMID- 1990996
TI  - Localized morphea after silicone gel breast implantation: more evidence for a
      cause-and-effect relationship.

PMID- 1990997
TI  - Acquired ichthyosis: a new cutaneous marker of autoimmunity.

PMID- 1990998
TI  - Classical and ulcerative lichen planus with plasma cell infiltrate.

PMID- 1990999
TI  - Malignant melanoma in human immunodeficiency virus type 2 infection.

PMID- 1991000
TI  - Oral mucosa pigmentation: a new side effect of azidothymidine therapy in patients
      with acquired immunodeficiency syndrome.

PMID- 1991001
TI  - Ranitidine for improvement of treatment-resistant psoriasis.

PMID- 1991002
TI  - Anti-beta-4 integrin antibody prominently stains nerves in psoriatic skin.

PMID- 1991003
TI  - Presentation of sebaceous carcinoma and dermatofibrosarcoma protuberans
      subsequent to intralesional interferon alfa-2b for the treatment of in situ
      squamous cell carcinoma.

PMID- 1991004
TI  - Gluten-free diet in dermatitis herpetiformis.

PMID- 1991006
TI  - Four-layer bandaging: an effective treatment for lower limb ulceration associated
      with arteriovenous malformation.

PMID- 1991005
TI  - Epilyt for scalp psoriasis.

PMID- 1991007
TI  - Diagnostic and therapeutic considerations for cutaneous Mycobacterium haemophilum
      infections.

PMID- 1991008
TI  - Supported employment: an alternative model for vocational rehabilitation of
      persons with severe neurologic, psychiatric, or physical disability.
AB  - Participation in paid work in competitive industry through placement in supported
      employment is compared and analyzed for 278 severely disabled persons.
      Differential outcomes are described for persons with chronic mental illness,
      cerebral palsy, traumatic brain injury, and dual diagnosis of chronic mental
      illness and mental retardation. Results indicated that supported employment
      appears to be an effective means of assisting these historically unemployable
      individuals to acquire and retain work. Cross-disability group differences were
      found in areas such as hourly wages, type of employment, services provided by
      employment specialists, and job retention. The results represent a baseline from
      which to evaluate future efforts at competitive work placement for persons with
      severe disabilities, using the supported-employment model.

PMID- 1991009
TI  - The disabled driver: an unmet challenge.
AB  - A survey was undertaken to determine if driving impairment secondary to a
      disabling injury is addressed in state licensing laws and training programs. In
      35 states drivers submit voluntarily to reevaluation after disabling injuries,
      but no provision is made for reporting such individuals. Only 15 states authorize
      physicians to report impaired drivers, and only seven require such reporting.
      Based on a survey of licensing bureaus in the capital or a major city of every
      state, clerks (who are likely to be the source of information to injured persons)
      are generally not aware of reporting requirements and supervisors are only
      slightly better informed. Of the 100 rehabilitation centers surveyed, only 36
      provided on-site training for disabled drivers. Voluntary submission for
      reevaluation after head injury does not often occur. Despite being asked to do
      so, none of the 35 head injured patients, followed up to two years post-onset,
      sought reevaluation, although 21 had resumed regular driving. Two of the 21 were
      involved in subsequent traffic accidents. Common guidelines need to be
      established across states to ensure reevaluation of individuals with disabling
      conditions, delivery of accurate information concerning licensing, and
      availability of training programs.

PMID- 1991010
TI  - Motor point delineation of the gluteus medius muscle for functional electrical
      stimulation: an in vivo anatomic study.
AB  - The purpose of this study was to delineate the motor point region of the gluteus
      medius muscle to aid in placing epimysial electrodes for functional electrical
      stimulation. Seven surgically dissected gluteus medius muscles were studied in
      five patients. The lateral surface of the muscle was sequentially probed with an
      electrical stimulator. The motor point region, which responded maximally to an
      applied electric current, was located on the posterolateral aspect of the muscle,
      adjacent to the superior margin of the piriformis, 3 cm lateral to the greater
      sciatic notch; it was rectangular or oval, measuring approximately 3.5 cm by 3.0
      cm. The mean threshold current that produced a contraction was 14 mA (range = 2
      to 26 mA). The mean minimum current required to produce a maximum contraction was
      34 mA (range = 11 to 60 mA). This information provides guidelines for the
      placement of electrodes for functional electrical stimulation of this deeply
      situated muscle, and it provides electrical stimulation parameters required for
      adequate muscle activation.

PMID- 1991011
TI  - Fatigue in postpolio syndrome.
AB  - A survey was conducted to better understand complaints of fatigue in patients
      previously diagnosed as having polio. Eighty-six individuals with postpolio
      syndrome and 20 healthy controls completed a questionnaire about their fatigue,
      the Beck Depression Inventory, and the CAGE questionnaire. The results showed
      that fatigue in postpolio syndrome usually occurred on a daily basis and
      increased in severity as the day progressed. Both the study group and controls
      described their fatigue as tiredness and a lack of energy. However, physical
      weakness was reported only in the postpolio group. Minimal physical exercise
      exacerbated fatigue in 48% of the postpolio group, whereas it diminished fatigue
      in 70% of the controls and in 15% of the postpolio group. Twenty-seven percent of
      the postpolio group and none of the controls reported mild to moderate depressive
      symptoms. However, depression, age, alcohol abuse, and employment status did not
      significantly affect the differences between groups in reported prevalence or
      description of chronic fatigue. Criteria to separate psychologic from organic
      causes of fatigue and treatment interventions are discussed.

PMID- 1991012
TI  - Spinal cord injury: prognosis for ambulation based on sensory examination in
      patients who are initially motor complete.
AB  - The purpose of this retrospective study was to document that patients with motor
      complete injury, but preserved pin appreciation, in addition to light touch,
      below the zone of injury have better prognoses with regard to ambulation than
      patients with only light touch preserved. Medical records were examined of all
      spinal cord injury (SCI) patients admitted between 1982 and 1988. Twenty-seven
      Frankel B patients with upper motor neuron lesions admitted within 72 hours of
      injury were identified. These patients were divided into two groups (B-1 and B
      2). Group B-1 (n = 18) were patients who had touch sensation but no pin
      appreciation below the zone of injury. Group B-2 (n = 9) were patients who had
      partial or complete pin appreciation and light touch below the zone of injury.
      The charts were examined for the patient's ability to walk independently using a
      reciprocal gait for at least 200 feet. The data were analyzed by the Fisher Exact
      test. Eight of the nine Group B-2 patients ambulated as compared to two of the 18
      Group B-1 patients (p less than .0002). Frankel B SCI patients with only touch
      preserved below the zone of injury had poor prognoses for ambulation; those with
      preserved pin appreciation below the zone of injury had excellent prognoses to
      regain functional ambulation.

PMID- 1991013
TI  - Psychosocial, functional, and quality of life assessment of patients with
      posttraumatic fracture nonunion, chronic refractory osteomyelitis, and lower
      extremity amputation.
AB  - One hundred nine patients with long-bone fracture nonunion, chronic refractory
      osteomyelitis, or posttraumatic amputation were evaluated for the impact of
      chronic disability on quality of life, as measured by the Arthritis Impact
      Measurement Scale (AIMS) and the Psychosocial Adjustment to Illness Scale (PAIS).
      A self-administered PAIS for spouses assessed psychosocial adjustment of spouses
      or significant others. A final questionnaire ranked the reasons for either
      continuing medical therapy or accepting amputation. The PAIS scores differed
      significantly between osteomyelitis patients and both nonunion and amputation
      patients (p less than .05). The presence or absence of pain produced significant
      differences in AIMS and PAIS scores of nonunion and osteomyelitis patients (p
      less than .05). Subscale analysis of AIMS scores revealed significant differences
      among the three groups in health perception and scale of orthopedic problem:
      osteomyelitis patients were more severely affected than nonunion or amputation
      patients. The PAIS detected no statistically significant difference in
      psychosocial adjustment of spouses of patients in the three population groups.
      The most common reason for continuing medical and surgical management of nonunion
      and osteomyelitis was expectation for cure. The amputee group chose ablation to
      avoid further treatment. Differences in psychosocial and functional ability were
      related to disease diagnosis, pain, status of fracture healing, and timing of
      amputation.

PMID- 1991015
TI  - Goal attainment scaling and outcome measurement in postacute brain injury
      rehabilitation.
AB  - Relationships among two-month and final goal attainment scaling (GAS) scores,
      preadmission and final Portland Adaptability Inventory (PAI) scores, and work
      outcome for 16 graduates of a comprehensive, postacute brain injury
      rehabilitation program were examined. Final GAS scores were higher for program
      graduates who obtained the most desirable work outcomes, and preadmission and
      final PAI scores were lower for the successful program graduates. Final GAS
      scores were significantly correlated with other outcome measures. Preadmission
      PAI scores predicted work outcome, and two-month GAS scores predicted final GAS
      scores. Initial PAI scores distinguished between program successes and failures,
      but not between program successes and dropouts. A brief look at one case
      illustrates the modified application of GAS in postacute brain injury
      rehabilitation. Results of this study and case analyses support GAS as a
      quantifiable, individualized measure that is useful for (1) monitoring patient
      progress, (2) structuring team conferences, (3) ongoing rehabilitation planning
      and decision-making, (4) concise, relevant communication to family, referral
      sources, and funding sources, and (5) overall program evaluation when used in the
      context of other objective outcome measures. Although our results support the
      clinical utility of GAS, further study is recommended to assess the psychometric
      characteristics of GAS in this application.

PMID- 1991014
TI  - Costs of operating a supported work program for traumatically brain-injured
      individuals.
AB  - This paper presents a preliminary analysis of costs associated with a return-to
      work program emphasizing a supported employment approach for persons who had
      sustained severe traumatic brain injuries. This analysis spans almost three
      years. Results indicated that a mean of 237.8 hours of staff intervention time
      was required to achieve job stabilization, at a cost of +6896. Ongoing follow
      along and support services averaged 1.64 hours per week at a cost of +47.56. Over
      68% of total staff time and costs were expended in job-site training and advocacy
      efforts. Application of these findings to state-level and agency-level policies
      should be weighed against individual characteristics and needs of clients,
      program design, and outcomes which clients achieve as a result of services.

PMID- 1991016
TI  - Factors predicting satisfactory home care after stroke.
AB  - This study prospectively investigated factors predicting optimal poststroke home
      care. One hundred and thirty-five first occurrence stroke patients and their
      primary support persons were evaluated during the initial hospitalization after
      stroke and again one year poststroke. Discriminant function analysis was used to
      identify two groups from the baseline data: home care situations which were rated
      optimal and those which were not. Group membership was predicted and validated
      with 72.6% accuracy. Patients at risk for less than optimal home care had
      caregivers who were (1) more likely to be depressed, (2) less likely to be
      married to the patient, (3) below average in knowledge about stroke care, and (4)
      reporting more family dysfunction. Our findings suggest that caregiver-related
      problems can have a collective effect on rehabilitation outcome and that
      treatment should reduce caregiver depression, minimize family dysfunction, and
      increase the family's knowledge about stroke care.

PMID- 1991017
TI  - Memory retraining to support educational reintegration.
AB  - A memory retraining package specifically designed to facilitate reintegration of
      head injured patients into an educational environment is described. Two
      adolescent patients who had severe head injuries were administered the memory
      retraining package approximately three months postinjury. A single case study and
      multiple baseline design was used to evaluate the efficacy of the memory
      retraining program. The results suggested that this is a promising avenue for
      improving memory functioning and facilitating educational reintegration, but only
      where moderate rather than severe memory deficits are involved. Studies involving
      groups of patients and the collection of data on generalization are required to
      confirm usefulness.

PMID- 1991018
TI  - Visual illusions in a patient with lateral medullary syndrome.
AB  - The disturbance of visual perception associated with nystagmus is a rare
      phenomenon. This is a case of a 61-year-old woman who developed progressive right
      hemisensory deficit, left facial sensory deficit, vertigo, staggering to the
      left, left ptosis, vertical diplopia, and ataxia of the left upper extremity. She
      had rotatory nystagmus in primary position, which increased in amplitude with
      left gaze. The above signs and symptoms were consistent with lateral medullary
      syndrome. During her rehabilitation, the patient complained of visual
      disturbances typical of oscillopsia. These disturbances, or illusions, are
      compensatory mechanisms for nystagmus and its resultant retinal error. The
      purpose of this case presentation was to study the pathophysiology underlying
      oscillopsia in patients with nystagmus and to stimulate awareness of such visual
      disturbances in stroke patients.

PMID- 1991019
TI  - A videofluoroscopy chair for the evaluation of dysphagia in patients with severe
      neuromotor disease.
AB  - Due to the difficulties encountered in positioning severely neurologically
      impaired individuals for videofluoroscopic studies, the Rehab Tech Video
      FluoroChair was developed. The purpose of the chair is to provide the severely
      disabled patient with safe, stable postural support in an upright position for
      videofluoroscopic studies, with anterior-posterior, lateral, and rotational views
      easily performed. The chair features a removable headrest, a full back support,
      armrests, lateral truncal supports, and a patented base which is clamped to the
      footboard of the radiology table and allows for 200 degrees rotation of the
      patient. Two case studies illustrate the practical use and versatility of the
      Rehab Tech Video FluoroChair.

PMID- 1991020
TI  - Thigh muscle symmetry.

PMID- 1991021
TI  - Lowman Award to Dr. June S. Rothberg.

PMID- 1991022
TI  - Chronologic age, time since injury, and time of measurement: effect on adjustment
      after spinal cord injury.
AB  - People are now living longer after spinal cord injury (SCI), yet only limited
      research has addressed the issue of aging and adjustment after SCI. The purpose
      of this study was to use a time-sequential design to identify the relationship
      between adjustment after SCI and three facets of aging; chronologic age, time
      since injury, and time of measurement. Life Situation Questionnaires were
      obtained from one sample of participants with SCI in 1974 (n = 256) and from a
      second sample in 1985 (n = 193). Participants were grouped into five cohorts
      based on chronologic age, five cohorts based on time since injury, and two groups
      based on time of measurement (1974, 1985). Two two-way MANOVA's were performed,
      one between chronologic age and time of measurement, and the other between time
      since injury and time of measurement. Results indicated that chronologic age and
      time since injury often worked in opposing directions; as some aspects of
      adjustment declined with greater chronologic age, but other aspects improved with
      increasing time since injury. Activity was strongly related to chronologic age,
      but medical stability was more strongly related to time since injury. Both
      chronologic age and time since injury were correlated with some aspects of life
      satisfaction. Comparisons between the two times of measurement (1974, 1985)
      indicated some limited positive changes in adjustment with time. The results
      point to the complexity of the relationship between aging and adjustment and the
      need for rehabilitation professionals to consider multiple aging factors.

PMID- 1991025
TI  - Control and function of the transamination pathways of glutamine oxidation in
      tumour cells.
AB  - Parallel investigations of the transamination pathways of glutamine oxidation in
      Ehrlich ascites carcinoma (EAC) and AS 30D hepatoma revealed that hepatoma cells,
      unlike EAC, produce very little aspartate. This cannot be explained by
      differences in the activity of glutamine-metabolizing enzymes. Also, the
      mitochondria from the hepatoma respired at a similar rate to EAC mitochondria
      with glutamine as sole substrate producing substantial amounts of aspartate.
      Unlike their isolated mitochondria, intact hepatoma cells showed a very low rate
      of glutamine oxidation. Compared with EAC, the rate of L-[U-14C]glutamine
      consumption by AS 30D hepatoma cells was much lower, with insignificant
      production of 14C-labelled aspartate and CO2. This suggested that the glutamine
      transporting system in the hepatoma cell plasma membrane had a very low activity.
      Isolated hepatoma mitochondria produced 3 times more pyruvate from malate than
      did EAC mitochondria, indicating a higher activity of NAD(P)-dependent malic
      enzyme. We postulate that an active malic enzyme may suppress the synthesis of
      aspartate in hepatoma cells, but further evidence is needed to confirm this
      assumption.

PMID- 1991024
TI  - Biosynthesis and processing of mitochondrial glutaminase in HTC hepatoma cells.
AB  - Rat HTC hepatoma cells were used to characterize the biosynthesis and processing
      of the renal isoenzyme of the mitochondrial glutaminase. Immunoblot analysis
      indicated that mitochondria isolated from HTC cells contained two prominent
      glutaminase peptides of 68 and 65 kDa and two minor peptides of 61 and 58 kDa.
      When the cells were labelled with [35S]methionine, the glutaminase-specific
      antibodies precipitated the same four polypeptides. However, when labelled in the
      presence of 5 microM-carbonyl cyanide m-chlorophenylhydrazone, an uncoupler of
      oxidative phosphorylation, only a 72 kDa cytoplasmic precursor of the
      mitochondrial glutaminase was immunoprecipitated. A comparison of the peptides
      generated by partial proteolysis of the precursor and the fully processed
      peptides indicates significant structural similarity. A 71 kDa form of the
      glutaminase was also observed when HTC cells were pulse-labelled for 2-6 min with
      [35S]methionine. Pulse-chase experiments indicate that the cytoplasmic precursor
      is quantitatively converted into the mature forms of the glutaminase. In
      addition, the observed kinetics established that the 71 kDa peptide is a true
      intermediate in the import of the mitochondrial glutaminase.

PMID- 1991026
TI  - Mechanism and control of degradation and resynthesis of adenylates in tumour
      cells.
AB  - A comparative study revealed that Ehrlich ascites carcinoma (EAC) cells use
      glutamine plus inosine for regeneration of adenylates via the purine nucleotide
      cycle, whereas AS 30D hepatoma cells use adenosine instead. This observation can
      be correlated with the very low production of aspartate from glutamine in
      hepatoma cells. Although glucose is an important energy fuel for EAC, it cannot
      maintain a high enough level of adenylates unless glutamine is also present.
      Kinetic analysis of hydrolysis of ATP and ADP in the presence of rotenone
      suggests that deamination of AMP does not maintain a high enough ATP/ADP ratio
      and probably does not act as energy buffer after inhibition of cell respiration.
      It seems that, compared with normal cells, malignant cells have the ability for a
      very rapid regeneration of adenylates. It is proposed that instability of the
      adenine nucleotide pool, owing to frequent aerobic-anaerobic transitions,
      represents an essential feature of neoplasia, with profound impact on the whole
      metabolism of tumour cells.

PMID- 1991027
TI  - Post-translational alterations in newly synthesized cartilage proteoglycans
      induced by the glutamine analogue 6-diazo-5-oxo-L-norleucine. Time course of
      inhibition and recovery.
AB  - Incorporation of [35S]sulphate by cultures of matrix-free cells from chick embryo
      sterna in the presence of the glutamine analogue 6-diazo-5-oxo-L-norleucine (0.58
      mM) was inhibited in a time-dependent manner to less than 15% of that in control
      cultures after 2 h. Characterization of the major cartilage proteoglycan
      synthesized under these conditions showed that it contained few, if any, normal
      sized chondroitin sulphate chains and only about half of the normal complement of
      substituted serine residues. Subsequent addition of D-glucosamine hydrochloride
      (final concn. 2 mM) resulted in a time-dependent recovery of [35S]sulphate
      incorporation to 90% of control cultures after 2 h, but restored the chondroitin
      sulphate chains to normal size within 15 min. On the basis of these results, it
      is concluded that a 2 h preincubation is necessary to deplete the chondrocytes of
      the endogenous supply of UDP-N-acetyl-D-glucosamine required for optimal
      glycoconjugate synthesis, and that this situation results in the synthesis of a
      chondroitin sulphate proteoglycan with significantly altered properties, owing to
      the paucity of glycosaminoglycan chains; however, this condition is completely
      reversible if the D-glucosamine pool is repleted.

PMID- 1991023
TI  - Function and regulation of expression of pulmonary surfactant-associated
      proteins.

PMID- 1991028
TI  - The non-catalytic C-terminal region of endoglucanase E from Clostridium
      thermocellum contains a cellulose-binding domain.
AB  - Mature endoglucanase E (EGE) from Clostridium thermocellum consists of 780 amino
      acid residues and has an Mr of 84,016. The N-terminal 334 amino acids comprise a
      functional catalytic domain. Full-length EGE bound to crystalline cellulose
      (Avicel) but not to xylan. Bound enzyme could be eluted with distilled water. The
      capacity of truncated derivatives of the enzyme to bind cellulose was
      investigated. EGE lacking 109 C-terminal residues (EGEd) or a derivative in which
      residues 367-432 of the mature form of the enzyme had been deleted (EGEb), bound
      to Avicel, whereas EGEa and EGEc, which lack 416 and 246 C-terminal residues
      respectively, did not. The specific activity of EGEa, consisting of the N
      terminal 364 amino acids, was 4-fold higher than that of the full-length enzyme.
      The truncated derivative also exhibited lower affinity for the substrate beta
      glucan than the full-length enzyme. It is concluded that EGE contains a cellulose
      binding domain, located between residues 432 and 671, that is distinct from the
      active site. The role of this substrate-binding domain is discussed.

PMID- 1991029
TI  - Ostrich crystallins. Structural characterization of delta-crystallin with enzymic
      activity.
AB  - Lens crystallins from the African ostrich (Struthio camelus) were isolated and
      characterized. Four crystallin fractions corresponding to alpha-, delta/beta- and
      beta-crystallins similar to those of duck crystallins were isolated, but epsilon
      crystallin was found to be absent. The native molecular masses and subunit
      structures of the purified fractions were analysed by gel filtration. SDS/PAGE
      and isoelectric focusing, revealing various extents of heterogeneity in each
      orthologous crystallin class. An ion-exchange chromatographic method was used for
      the large-scale preparation of delta-crystallin suitable for structural and
      enzymic studies. It was unexpectedly found that the purified native delta
      crystallin of ostrich lens possessed high argininosuccinate lyase activity, in
      contrast with chicken delta-crystallin. The c.d. spectra indicated a predominant
      beta-sheet structure in alpha- and beta-crystallins, and a significant
      contribution of alpha-helical structure in the delta-crystallin fraction. The
      estimate of secondary structures from c.d. spectroscopy for each crystallin class
      bears a resemblance to that of duck crystallins, except that ostrich delta
      crystallin possesses much less helical content than duck delta-crystallin.
      Comparison of crystallin compositions and structures from aquatic and terrestrial
      birds revealed distinct differences.

PMID- 1991030
TI  - Fucose content of keratan sulphates from bovine articular cartilage.
AB  - Alkaline-borohydride-reduced keratan sulphate chains were isolated from bovine
      articular cartilage (6-8-year-old animals). Nine keratan sulphate fractions of
      increasing molecular weight were prepared by gel-permeation chromatography on a
      calibrated column of TSK 30 XL. The samples were analysed for fucose and
      galactose contents (% by wt. of keratan sulphate) and fucose/galactose ratio. The
      fucose content increased with molecular size, but the galactose content remained
      constant. It was concluded that the alpha(1----3)-linked fucose [Thornton,
      Morris, Cockin, Huckerby, Nieduszynski, Carlstedt, Hardingham & Ratcliffe (1989)
      Biochem. J. 260, 277-282] was located within the poly-N-acetyl-lactosamine repeat
      sequence of articular-cartilage keratan sulphate.

PMID- 1991031
TI  - Identification of valine/leucine/isoleucine and threonine/alanine/glycine proton
      spin systems of Escherichia coli adenylate kinase by selective deuteration and
      selective protonation.
AB  - Adenylate kinase from two types of Escherichia coli strains, a wild-type and a
      leucine-auxotrophic strain, was purified. On the one hand, growing the leucine
      auxotrophic bacteria on a medium containing deuterated leucine yielded E. coli
      adenylate kinase with all leucine residues deuterated. On the other hand, by
      growing the wild-type bacteria on deuterated medium with phenylalanine, threonine
      and isoleucine present as protonated specimens, 80% randomly deuterated enzyme
      with protonated phenylalanine, threonine and isoleucine residues could be
      prepared. Use of these proteins enabled identification of the spin systems of
      these amino acid residues in the n.m.r. spectra of the protein.

PMID- 1991032
TI  - Inositol 1,3,4,6-tetrakisphosphate mobilizes calcium in Xenopus oocytes with high
      potency.
AB  - Injection of Ins(1,3,4,6)P4 into Xenopus oocytes evoked Ca2(+)-dependent membrane
      currents with a potency 5-10 times less than Ins(1,4,5)P3, whereas Ins(1,3,4)P3
      and Ins(1,3,4,5,6)P5 were almost ineffective. Responses to Ins(1,3,4,6)P4 arose
      through liberation of intracellular Ca2+ and through entry of extracellular Ca2+.
      These results, together with the observation that Ins(1,3,4,6)P4 facilitated
      responses to Ins(1,4,5)P3, suggests that both of these compounds may act on the
      same intracellular receptors.

PMID- 1991034
TI  - Biochemical characterization of the native tissue form of type X collagen from
      embryonic chick sternal cartilage and identification of a chymotrypsin-sensitive
      site within its triple-helical domain.
AB  - We isolated and characterized the intact native tissue form of type X collagen
      from the presumptive calcification region of lathyritic chick-embryo sterna and
      from organ cultures incubated in the presence of beta-aminopropionitrile (beta
      APN). The administration of beta-APN in vivo greatly increased the solubility of
      type X collagen and allowed the extraction of quantitative amounts of these
      molecules under non-denaturing non-proteolytic conditions. Biosynthetic studies
      in vitro showed that the addition of beta APN during labelling resulted in a 4
      fold increase in the extractability of the newly synthesized type X collagen.
      Biochemical characterization of the intact type X collagen extracted from the
      tissues or biosynthesized in the organ cultures showed that type X collagen is
      composed of 59,000-Mr chains that do not undergo conversion into shorter
      polypeptides. Despite the marked solubilization of type X collagen upon
      administration of beta APN, a substantial proportion remained tissue-bound and
      could only be extracted by employing proteolytic digestion followed by disulphide
      bond reduction. These findings indicate that type X collagen in the tissues is
      stabilized by at least two different mechanisms, one involving beta APN-sensitive
      cross-links and the second through interactions with disulphide-bonded proteins.
      Limited proteolytic digestion with chymotrypsin of tissues containing 1.0 M-NaCl
      insoluble type X collagen resulted in its complete solubilization. The majority
      of type X collagen molecules extracted with chymotrypsin were approx. 10% shorter
      than those obtained after limited pepsin digestion (Mr 40,000 versus Mr 45,000)
      and showed the selective loss of a single CNBr-cleavage peptide. These findings
      indicate the existence of chymotrypsin-sensitive sites within the triple-helical
      domain of the molecules.

PMID- 1991033
TI  - Variation in the expression of Mu-class glutathione S-transferase isoenzymes from
      human skeletal muscle. Evidence for the existence of heterodimers.
AB  - The cytosolic glutathione S-transferases (GST) from human skeletal muscle were
      purified by a combination of affinity chromatography and anion-exchange
      chromatography followed by either chromatofocusing or hydroxyapatite
      chromatography. Pi-class and Mu-class GST, but not Alpha-class GST, were isolated
      from muscle. In addition to a Pi-class GST subunit, which exists as a homodimer,
      this tissue also contains a total of three distinct neutral-type Mu-class GST
      subunits, which hybridize to form homodimers or heterodimers. The neutral-type
      subunits are referred to as N1-N3 and are defined by the decreasing isoelectric
      points of the homodimers; GST N1N1, N2N2 and N3N3 have estimated pI values of
      6.1, 5.3 and less than 5.0 respectively. SDS/PAGE showed that N1, N2 and N3 have
      Mr values of 26,700, 26,000 and 26,300 respectively. The N1, N2 and N3 subunits
      are catalytically distinct, with N1 possessing a high activity for trans-4
      phenylbut-3-en-2-one and N2 having high activity with 1,2-dichloro-4
      nitrobenzene. In skeletal muscle the expression of the N1 subunit, but not of N2
      and N3 subunits, was found to differ from specimen to specimen. The N1 subunit
      was absent from about 50% of samples examined, and the purification results from
      two different specimens are presented to illustrate this inter-individual
      variation. Skeletal muscle from one individual (M1), which did not express N1,
      contained only GST N2N2, N2N3 and pi, whereas the second sample examined (M2)
      contained GST N1N2, N2N2 and N2N3 as well as GST pi. N-Terminal amino acid
      sequence analysis supported the electrophoretic evidence that the N2 subunit in
      GST N1N2, N2N2 and N2N3 represents the same polypeptide. The peptides obtained
      from CNBr digests of N2 were subjected separately to automated amino acid
      sequencing, and the results indicate that N2 is distinct but closely related to
      the protein encoded by the human Mu-class cDNA clone GTH4 [DeJong, Chang, Whang
      Peng, Knutsen & Tu (1988) Nucleic Acids Res. 16, 8541-8554]. GST N2N2 is probably
      identical with GST 4 [Board, Suzuki & Shaw (1988) Biochim. Biophys. Acta 953, 214
      217], as over the 24 N-terminal residues of GST 4 there is complete identity
      between the two enzymes. Our data suggest that the GST 1 and GST 4 loci are part
      of the same multi-gene family.

PMID- 1991035
TI  - Correlations between cardiac protein synthesis rates, intracellular pH and the
      concentrations of creatine metabolites.
AB  - We have examined in detail the correlations between protein synthesis rates,
      intracellular pH (pHi) and the concentrations of creatine metabolites in the rat
      heart perfused anterogradely in vitro. Using perfusion buffers ranging from pH
      7.2 to 8.2 at 37 degrees C, we were able to manipulate pHi from between 7.24 to
      7.66, i.e. from the slightly acidotic to the alkalinotic as compared with the
      physiological values of pHi (about pH 7.29). The dependence of pHi on
      extracellular pH (pHo) was linear, with the value of delta pHi/delta pHo being
      0.4-0.5. Protein synthesis rates were significantly stimulated when pHi was
      increased above its physiological value, and they were strongly correlated with
      pHi. They were also strongly correlated with phosphocreatine concentrations (and
      with creatine concentrations and phosphocreatine/creatine concentration ratios).
      Adenine nucleotide (ATP, ADP and AMP) concentrations and the ATP/ADP
      concentration ratio were not systematically altered by manipulating pHi, and
      protein synthesis rates showed only a relatively weak dependence on these
      variables. Since creatine kinase catalyses a reaction that is close to
      equilibrium in the perfused heart, and since phosphorylation of creatine involves
      release of a proton, we argue that the changes in phosphocreatine and creatine
      concentrations are manifestations of alterations in pHi. In this regard, we show
      that [log[( phosphocreatine]/[creatine]) + log [( ADP]/[ATP])] [the value of
      which gives [pHi--log (mass action ratio)]] is positively correlated with pHi,
      although the slope of the line is 0.7, as opposed to the ideal value of unity. We
      discuss three hypotheses to account for our observations: (i) protein synthesis
      rates are influenced directly by pHi, (ii) pHi affects the concentrations of
      creatine metabolites, which in turn affect protein synthesis rates, and (iii) pHi
      affects the value of an unidentified co-variable, which in turn affects protein
      synthesis.

PMID- 1991036
TI  - Differential segregation of human and hamster cathepsin D in transfected baby
      hamster kidney cells.
AB  - The segregation of human cathepsin D, studied in baby-hamster kidney cells (BHK)
      transfected with human cathepsin D cDNA and compared with that of hamster
      cathepsin D in the same cells, showed that, in cells that expressed human
      cathepsin D at a low rate, most of the enzyme remained intracellular. In
      contrast, when the enzyme was expressed at a high rate, most was secreted. The
      segregation was examined with an anti-(human cathepsin D) antibody that reacted
      with the human enzyme exclusively and an anti-(rat cathepsin D) antibody that
      reacted with both enzymes. In one protocol the cells were metabolically labelled
      and the two antibodies were used in sequence to precipitate the enzymes from
      extracts of cells and medium. High expression of the human enzyme did not
      interfere with the segregation of hamster cathepsin D. In another protocol the
      activity of cathepsin D in cells and medium was measured before and after
      titration with anti-(human cathepsin D) antiserum. Human cathepsin D was found
      predominantly in the medium, and hamster cathepsin D mainly in the cells. In the
      presence of 10 mM-NH4Cl the intracellular segregation of hamster cathepsin D was
      strongly inhibited, while the segregation of human cathepsin D was only slightly
      diminished. In BHK cells, at least two systems participate in the sorting of the
      two cathepsins, one of them being rather insensitive to NH4Cl.

PMID- 1991037
TI  - Effects of hypothyroidism on the metabolism of lipid emulsion models of
      triacylglycerol-rich lipoproteins in rats.
AB  - Methimazole-treated hypothyroid rats were injected intravenously with
      triacylglycerol/cholesteryl oleate/cholesterol/phospholipid emulsions designed to
      model the composition of chylomicrons. Compared with controls, hypothyroidism
      decreased the clearance rates of emulsion cholesteryl oleate. Clearance of
      emulsion triolein was affected much less and could be accounted for by residual
      triolein in remnants, suggesting that triacylglycerol lipolysis by lipoprotein
      lipase was unaffected by hypothyroidism but that clearance of remnants from
      plasma was decreased. Assays in vitro showed increased activities of lipoprotein
      lipase and hepatic lipase in hypothyroid rats. Emulsions were incubated with post
      heparin plasma lipoprotein lipase to prepare remnants in vitro. The clearance
      from plasma of pre-formed remnants was slower after injection into hypothyroid
      rats than in control rats. Uptake of remnant cholesteryl oleate by the liver was
      significantly decreased in the hypothyroid rats. Treatment of hypothyroid rats
      for 7 days with 3,3',5'-tri-iodo-L-thyronine (T3) reversed the inhibition of
      hepatic remnant uptake and normalized plasma cholesterol. A thyroid hormone
      analogue with decreased hypermetabolic side-effects, L-94901, attenuated plasma
      cholesterol and improved but did not normalize remnant clearance. Emulsions
      incubated with plasma from hypothyroid rats had a decreased ratio of
      apolipoprotein E/apolipoprotein C compared with control rats or hypothyroid rats
      treated with T3. The change in the apolipoprotein E/apolipoprotein C ratio
      probably accounts for the defect in remnant clearance in hypothyroidism.

PMID- 1991038
TI  - Avidin acylation prevents the complement-dependent lysis of avidin-carrying
      erythrocytes.
AB  - Non-covalent binding of avidin to biotinylated erythrocytes results in complement
      dependent haemolysis. Biotinylated erythrocytes, as well as native cells, are not
      lysed by complement. Complement activation requires a tight contact between
      avidin and the erythrocyte membrane, since avidin does not in itself activate
      complement and does not inhibit lysis of sensitized sheep erythrocytes. The
      efficiency of haemolysis depends on avidin's surface density. When the avidin
      concentration in the reaction mixture is less than 15 micrograms/ml, erythrocyte
      lysis is not induced. However, the attachment of biotinylated antibodies to
      avidin-carrying erythrocytes decreases dramatically. Acylation of avidin with
      succinic anhydride strongly decreases its ability to induce complement-dependent
      haemolysis. However, the ability of avidin to cross-link the biotin-containing
      structures decreases after acylation. A 50% modification of avidin by succinic
      anhydride (pI about 7.0) allows preparation of 'immunoerythrocytes', which retain
      their affinity to antigen and stability in the presence of complement.

PMID- 1991040
TI  - Pyruvate carboxylase catalysis of phosphate transfer between carbamoyl phosphate
      and ADP.
AB  - In a reaction that is analogous to the phosphorylation of ADP from
      carboxyphosphate, pyruvate carboxylase catalyses the formation of ATP from
      carbamoyl phosphate and ADP at a rate that is about 0.3% of the pyruvate
      carboxylation reaction and about 3% of the full reverse reaction. Acetyl-CoA
      stimulates the phosphorylation of ADP from carbamoyl phosphate but is not an
      essential requirement of the reaction. Mg2+ also stimulates the reaction, and in
      the range of Mg2+ concentrations considered the effect of V is much larger in the
      absence of acetyl-CoA than in its presence. Acetyl-CoA and Mg2+ may be acting in
      a co-operative way to stimulate the phosphorylation of ADP in a similar way to
      their effects on the pyruvate-carboxylation reaction. The phosphorylation of ADP
      by carbamoyl phosphate is also stimulated by the presence of biotin in the part
      of the active site where this reaction occurs, but again it is not absolutely
      required for the reaction to proceed. The pH profiles of the phosphorylation of
      ADP by carbamoyl phosphate indicate that there are at least two ionizable
      residues involved in the reaction, one of which probably has a role in the
      release of carbamate from the active site.

PMID- 1991039
TI  - Activity of influenza C virus O-acetylesterase with O-acetyl-containing
      compounds.
AB  - Influenza C virus (strain C/Johannesburg/1/66) was grown, harvested, purified and
      used as source for the enzyme O-acetylesterase (N-acyl-O-acetylneuraminate O
      acetylhydrolase; EC 3.1.1.53). This activity was studied and characterized with
      regard to some new substrates. The pH optimum of the enzyme is around 7.6, its
      stability at different pH values shows a result similar to that of the pH
      optimum, and its activity is well maintained in the pH range from 7.0 to 8.5 (all
      these tests were performed with 4-nitrophenyl acetate as substrate). Remarkable
      differences were found in the values of both Km and Vmax, with the synthetic
      substrates 4-nitrophenyl acetate, 2-nitrophenyl acetate, 4-methylumbelliferyl
      acetate, 1-naphthyl acetate and fluorescein diacetate. The use of 4-nitrophenyl
      acetate, 4-methylumbelliferyl acetate or 1-naphthyl acetate as substrate seems to
      be convenient for routine work, but it is better to carry out the measurements in
      parallel with those on bovine submandibular gland mucin (the latter is a natural
      and commercially available substrate). It was found that 4-acetoxybenzoic acid,
      as well as the methyl ester of 2-acetoxybenzoic acid, but not 2-acetoxybenzoic
      acid itself, are cleaved by this enzyme. Triacetin, di-O-acetyladenosine, tri-O
      acetyladenosine, and di-O-acetyl-N-acetyladenosine phosphate, hitherto unreported
      as substrates for this viral esterase, are hydrolysed at different rates by this
      enzyme. We conclude that the O-acetylesterase from influenza C virus has a broad
      specificity towards both synthetic and natural non-sialic acid-containing
      substrates. Zn2+, Mn2+ and Pb2+ (as their chloride salts), N-acetylneuraminic
      acid, 4-methyl-umbelliferone and 2-acetoxybenzoic acid (acetylsalicylic acid) did
      not act as inhibitors.

PMID- 1991041
TI  - Oxidative damage to hyaluronate and glucose in synovial fluid during exercise of
      the inflamed rheumatoid joint. Detection of abnormal low-molecular-mass
      metabolites by proton-n.m.r. spectroscopy.
AB  - Proton Hahn spin-echo n.m.r. spectroscopy was employed to detect abnormal
      metabolites present in rheumatoid synovial fluid that are derived from the
      deleterious generation of reactive oxygen radical species during exercise of the
      inflamed rheumatoid joint. A resonance attributable to a low-molecular-mass N
      acetylglucosamine-containing oligosaccharide formed by the oxygen-radical
      mediated depolymerization of synovial-fluid hyaluronate was clearly demonstrable
      when subjects with inflammatory joint disease were exercised. Moreover, formate,
      which may be derived from the attack of OH.radical on synovial-fluid
      carbohydrates, was also readily detectable in these samples. gamma-Radiolysis of
      rheumatoid synovial fluid samples and aqueous solutions of hyaluronate also gave
      rise to the production of the low-molecular-mass hyaluronate-derived
      oligosaccharide species and markedly elevated concentrations of (non-protein
      bound) formate in the biological fluids. As expected, corresponding spectra of
      gamma-irradiated blood serum samples obtained from normal volunteers did not
      contain the signal attributable to the low-molecular-mass oligosaccharide
      species, but the formate resonance (barely detectable in non-irradiated normal
      serum samples) became clearly visible. Additionally, a curious increase in the
      effective concentration of non-protein-bound low-molecular-mass metabolites such
      as acetate, citrate, lactate and glutamine was observed after gamma-radiolysis of
      all biological fluids studied. The hyaluronate-derived low-molecular-mass
      oligosaccharide species and formate are suggested as novel markers of reactive
      oxygen radical activity in the inflamed rheumatoid joint during exercise-induced
      hypoxic/reperfusion injury.

PMID- 1991042
TI  - DNA methylase from Pisum sativum.
AB  - DNA methylase activity was detected in nuclei from pea shoots. The enzyme can
      only be extracted by low-salt treatment if the nuclei are pretreated with
      micrococcal nuclease. Only a single enzyme was detected, and it was purified to a
      specific activity of 1620 units/mg of protein. It has an Mr of 160,000 on gel
      filtration and SDS/PAGE. Pea DNA methylase methylates cytosine in all four
      dinucleotides, and this is interpreted to show that it acts on CNG
      trinucleotides. Although it shows a strong preference for hemi-methylated double
      stranded DNA, it is also capable of methylation de novo. Homologous DNA is the
      best natural substrate. In vitro the enzyme interacts with DNA to form a salt
      resistant complex with DNA that is stable for at least 4 h.

PMID- 1991043
TI  - Evidence that the inhibition sites of the neurotoxic amine 1-methyl-4
      phenylpyridinium (MPP+) and of the respiratory chain inhibitor piericidin A are
      the same.
AB  - 1-Methyl-4-phenylpyridinium (MPP+), the neurotoxic bioactivation product of 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), interrupts mitochondrial
      electron transfer at the NADH dehydrogenase-ubiquinone junction, as do the
      respiratory chain inhibitors rotenone, piericidin A and barbiturates. Proof that
      these classical respiratory chain inhibitors and MPP+ react at the same site in
      the complex NADH dehydrogenase molecule has been difficult to obtain because none
      of these compounds bind covalently to the target. The 4'-alkyl derivatives of
      MPP+ inhibit NADH oxidation in submitochondrial particles at much lower
      concentrations than does MPP+ itself, but still dissociate on washing the
      membrane preparations, with consequent re-activation of the enzyme. The MPP+
      analogues with short alkyl chains prevent the binding of 14C-labelled piericidin
      A to the membrane and thus must act at the same site, but analogues with alkyl
      chains longer than heptyl do not prevent binding of [14C]piericidin.

PMID- 1991044
TI  - The roles of different protein kinases and of calmodulin in the effects of Ca2+
      mobilization on 3-hydroxy-3-methylglutaryl-CoA reductase activity in isolated rat
      hepatocytes.
AB  - The roles of protein kinase C, Ca2+/calmodulin-dependent protein kinase and AMP
      activated protein kinase in the phosphorylation of 3-hydroxy-3-methylglutaryl-CoA
      (HMG-CoA) reductase induced by Ca2(+)-mobilizing conditions in isolated
      hepatocytes were investigated. Only partial evidence for the involvement of AMP
      activated kinase was found. Antagonism of calmodulin action prolonged the
      decrease in expressed/total activity ratio induced by vasopressin plus glucagon.
      Protease inhibitors active against Ca2(+)-dependent cytosolic proteases or
      lysosomal proteolysis did not attenuate the loss of total HMG-CoA reductase
      induced by glucagon plus vasopressin, but calmodulin antagonists largely
      prevented this effect.

PMID- 1991045
TI  - Exocytosis in neurohypophysial nerve terminals is not coupled to protein kinase C
      translocation.
AB  - Protein kinase C (PKC) has been implicated in the mechanism of exocytosis,
      although various studies have been unable to pinpoint actual translocation or
      activation of PKC during exocytosis. We have studied, in neurohypophysial nerve
      endings, intracellular Ca2+ levels, secretion of neuropeptides and PKC
      translocation. Neurohormone secretion was triggered by K(+)-induced or
      electrically induced depolarization in both the absence and the presence of
      phorbol esters. PKC was translocated from the cytosol to the membrane on
      electrical stimulation or K+ depolarization, but not to the extent obtained with
      phorbol ester. Data are presented clearly demonstrating that the translocation of
      PKC from cytosol to membrane is not required for exocytosis, nor does it alter in
      any way neuropeptide release from neurohypophysial nerve terminals.

PMID- 1991046
TI  - The P450 superfamily: update on new sequences, gene mapping, and recommended
      nomenclature.
AB  - We provide here a list of 154 P450 genes and seven putative pseudogenes that have
      been characterized as of October 20, 1990. These genes have been described in a
      total of 23 eukaryotes (including nine mammalian and one plant species) and six
      prokaryotes. Of 27 gene families so far described, 10 exist in all mammals. These
      10 families comprise 18 subfamilies, of which 16 and 14 have been mapped in the
      human and mouse genomes, respectively; to date, each subfamily appears to
      represent a cluster of tightly linked genes. We propose here a modest revision of
      the initially proposed (Nebert et al., DNA 6, 1-11, 1987) and updated (Nebert et
      al., DNA 8, 1-13, 1989) nomenclature system based on evolution of the
      superfamily. For the gene we recommend that the italicized root symbol CYP for
      human (Cyp for mouse), representing cytochrome P450, be followed by an Arabic
      number denoting the family, a letter designating the subfamily (when two or more
      exist), and an Arabic numeral representing the individual gene within the
      subfamily. A hyphen should precede the final number in mouse genes. We suggest
      that the human nomenclature system be used for other species. This system is
      consistent with our earlier proposed nomenclature for P450 of all eukaryotes and
      prokaryotes, except that we are discouraging the future use of cumbersome Roman
      numerals.

PMID- 1991047
TI  - Rat liver cytochrome P450IA2 synthesized by transfected COS-1 cells efficiently
      activates food-derived promutagens.
AB  - A standard calcium phosphate technique was used to obtain transient expression of
      cDNAs for rat liver cytochrome P450s in COS-1 cells. Cells transfected with a
      pMT2-based vector expressing P450IA2 cDNA (pMT2-IA2) had high acetanilide-4
      hydroxylase activity and very low aryl hydrocarbon hydroxylase (AHH) activity.
      Cells transfected with a hybrid expression vector, pMT2-IA2/IA1, coding for a
      P450IA2/IA1 fusion protein (consisting of the amino-terminal region of P450IA2
      and the central and carboxy-terminal regions of P450IA1) had high AHH activity.
      This result and other data indicate that the P450IA2/IA1 fusion protein has the
      substrate specificity of P450IA1. Extracts of cells transfected with pMT2-IA2
      readily converted 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) and related
      food-derived promutagens into mutagenic forms. Extracts of cells transfected with
      pMT2-IA2/IA1 showed efficient activation of 3-amino-1-methyl-5H-pyrido[4,3
      b]indole (Trp P-2). To facilitate comparison of activities of P450s synthesized
      from cDNA expression vectors, the promutagen activation assays were carried out
      with limiting enzyme and saturating or nearly saturating substrate
      concentrations. The transient expression system described here uses a standard
      expression vector and requires only microgram quantities of cell extract protein
      for activation of food-derived promutagens such as MeIQ and Trp P-2. It will be
      useful for identifying P450s active in promutagen activation and for analyzing
      structure-function relationships of different P450 molecules.

PMID- 1991048
TI  - Genomic organization and DNA sequence of the mouse kidney androgen-regulated
      protein (KAP) gene.
AB  - The gene for kidney androgen-regulated protein (KAP) is expressed under
      androgenic control in the epithelial cells of the renal cortical proximal
      tubules. However, there is an androgen-independent component of the expression of
      this gene that occurs specifically in the outermedullary S3 segments of the
      proximal tubules. In these cells, the KAP gene is estrogen responsive and its
      expression is dependent on pituitary function. As a first step in correlating its
      interesting cell-specific and hormonal regulation with the structure of the gene,
      the genomic organization of the KAP gene was described and sequence of the gene
      and the proximal 1 kb of 5'-flanking DNA was determined. Sequence motifs were
      identified in the 5'-flanking DNA that may function in the regulation KAP gene
      expression by androgen, estrogen, and pituitary glycoprotein hormones. The gene
      is present in a single copy in the mouse genome and is 3,807 nucleotides in
      length. It contains 4 exons of 120, 177, 63, and 251 nucleotides and three
      intervening sequences of 1,450, 126, and 1,620 nucleotides. The gene exhibits a
      high degree of a genetic polymorphism as revealed by comparison of restriction
      digests of DNA from two highly inbred strains, BALB/c and C57BL/6.

PMID- 1991049
TI  - Characterization and expression of the prostatic arginine esterase gene, a canine
      glandular kallikrein.
AB  - The prostatic arginine esterase gene was isolated from a genomic library prepared
      with dog liver DNA in lambda EMBL3. The selected clone contained an insert of
      approximately 17 kb which included the whole coding portion of arginine esterase
      mRNA (5 exons plus 4 introns), 2 kb upstream from the initiation site and 12 kb
      downstream from the polyadenylation site. The intron-exon boundaries were
      identical to all known mammalian kallikrein genes. The deduced amino acid
      sequence indicated a high degree of identity (51-61%) with other kallikreins
      expressed not only in the prostate but also in the pancreas of various animal
      species. The 5'-flanking sequences contained potential regulatory elements such
      as a variant TATA box (TTTAAA), a CCAAT box, a SP1 transcriptional factor binding
      site (GGGCGG), and two TGTCCT motifs resembling glucocorticoid response elements.
      Southern blot analysis with an amplified cDNA fragment of 487 bp corresponding to
      the 5' portion of the mRNA and with a DNA probe from a different portion of the
      arginine esterase gene indicated the presence of two to three homologous genes in
      the canine genome while in a previous study a single band was detected using a
      400-bp arginine esterase cDNA corresponding to the 3' portion of the mRNA. These
      results suggest that the arginine esterase gene belongs to a small kallikrein
      gene family. Arginine esterase mRNA is expressed primarily in the prostate but
      also at an extremely low level (approximately a thousandfold less) in several
      other tissues including the liver, the gracilis thigh muscle, the kidney, and the
      pancreas.

PMID- 1991050
TI  - The transcriptional factor Egr-1 is synthesized by baculovirus-infected insect
      cells in an active, DNA-binding form.
AB  - The Egr-1 (zfp-6) gene encodes a zinc-finger-containing nuclear protein that is
      rapidly and transiently induced in quiescent cells treated with mitogens. We have
      constructed baculovirus vectors that synthesize mouse Egr-1 protein initiating at
      two putative ATG start sites. The ATG site producing the larger protein (Mr,
      80,000) is similar, if not identical, to Egr-1 synthesized by serum-stimulated
      quiescent mouse fibroblasts, thus identifying the likely site for translation.
      The protein synthesized by the insect cells is active as assayed by its ability
      to bind to a specific DNA sequence that has been identified as an Egr-1 binding
      site. The insect cell system will allow further studies of the structure and
      function of the Egr-1 product, a protein that appears to be an important "master
      switch" for other genes.

PMID- 1991051
TI  - Shuttle vector plasmid propagation in human peripheral blood lymphocytes
      facilitated by liposome-mediated transfection.
AB  - Transfection of human peripheral blood lymphocytes facilitated by a positively
      charged liposome preparation (Lipofectin, BRL) is 100-fold more efficient than
      the DEAE dextran technique for the uptake and replication of shuttle vector
      plasmid DNA. The yield of progeny plasmids obtained from 10 ml of blood was high
      enough for mutational analysis. A marked increase in the mutation frequency of
      the shuttle vector marker gene was noted in response to the induction of psoralen
      adducts in the vector. By using normal human lymphocytes, this method will permit
      shuttle vector analysis of DNA repair and mutagenesis in a large number of
      individuals. This method could also prove useful for studies of human
      lymphotropic viruses.

PMID- 1991052
TI  - Fellowship proliferation. Part I: Impact and long-range trends.

PMID- 1991053
TI  - Monocortical miniplate fixation of mandibular angle fractures.
AB  - Noncompression monocortical miniplate fixation of mandibular fractures has become
      a reliable method of providing rigid fixation and eliminating the need for
      intermaxillary fixation. Recent studies, using a variety of internal fixation
      techniques, have described high complication rates at the mandibular angle. This
      article compares the use of one miniplate vs two miniplates in treatment of angle
      fractures. Since September 1985, 61 patients with 63 mandibular angle fractures
      have been treated with miniplates. Forty-four fractures were fixed with two
      miniplates. Six complications (3.1%) occurred, five of which were in the one
      miniplate group. The complication rate in the double-miniplate group is the
      lowest reported of any plating technique. The use of two miniplates has proved to
      be an effective method of treating mandibular angle fractures.

PMID- 1991054
TI  - External fixation using microplates after laryngotracheal expansion surgery. An
      animal study.
AB  - Management of severe laryngotracheal stenosis requires treatment with open
      laryngeal surgical approaches. Performing the necessary anterior, and possibly
      posterior, incisions to expand the cricoid and tracheal rings causes instability
      of the segments. Placing an intraluminal stent has several disadvantages, ranging
      from injury of healthy tissue to airway obstruction. The availability of an
      external stent would avoid many of these complications. We performed expansion
      laryngeal surgery in dogs and explored the use of microplates for external
      fixation and determined the surgical outcome if no fixation is used. The results
      show that microplates are very effective in maintaining external fixation and
      that a need for placing an intraluminal stent when a posterior cricoid split is
      performed exists.

PMID- 1991056
TI  - Clinical research in otolaryngology journals.
AB  - In an era of cost-effectiveness and quality control, the need for sound clinical
      research as a basis for health care decisions has intensified. To identify trends
      in clinical research, a survey of 1831 articles in four otolaryngology journals
      spanning a 20-year period was performed. Clinical research comprised 77% of all
      articles and has steadily increased in volume. Significant trends have occurred
      toward multiple authorship, more female first authors, and a declining proportion
      of articles with grant support. In 1989, a total of 224 articles (40%) employed
      analytic or experimental study designs vs only 64 articles (18%) in 1969.
      Descriptive studies and review articles have declined in prevalence. These
      findings suggest that over the past two decades, clinical research in
      otolaryngology journals has increased in both quantity and quality.

PMID- 1991055
TI  - Vasoconstrictors in facial plastic surgery.
AB  - The effectiveness of local anesthetics is improved by the addition of a
      vasoconstrictor with an increased duration of action and the ability to decrease
      both systemic toxic reactions and local bleeding. Epinephrine, the standard drug
      for vasoconstriction, has some limitations due to potential cardiac and local
      toxic effects. Using an animal model, we compared the effects of various
      concentrations of epinephrine and two other vasoconstrictors, phenylephrine
      hydrochloride and felypressin, on local blood flow. We also examined the local
      effects of bupivacaine hydrochloride and ropivacaine hydrochloride, a new local
      anesthetic. We found that felypressin was as effective a vasoconstrictor as
      epinephrine, with fewer potential toxic reactions. Phenylephrine (Neo
      Synephrine), on the other hand, was less effective, with a shorter duration of
      action. As expected, bupivacaine produced vasodilation, while ropivacaine was
      found to have vasoconstrictive properties.

PMID- 1991057
TI  - Single-stage laryngotracheal reconstruction.
AB  - The mainstay for repairing subglottic and tracheal stenosis has been the rib
      graft with prolonged stenting. A refinement of this treatment was the use of the
      anterior cricoid decompression (split). We present single-stage reconstruction of
      the airway as an additional refinement of the laryngotracheoplasty. This article
      describes the experience of two institutions with single-stage reconstruction and
      offers some observations on the principles of the technique.

PMID- 1991058
TI  - Culture-positive allergic fungal sinusitis.
AB  - Allergic Aspergillus sinusitis is a well-defined clinical and histologic entity,
      although surprisingly few reported cases have yielded any fungal growth on
      culture. Taking advantage of recent changes in the identification and
      classification of certain groups of fungi, we were able to identify a specific
      fungal organism in 19 of 22 consecutive patients with a histologic diagnosis of
      allergic fungal sinusitis over the past 2 1/2 years. Aspergillus was found in
      only one patient, while an organism in the family of dematiaceous fungi was found
      in 18 patients. Of these patients, the genus Bipolaris was the most commonly
      represented, while Exserohilum, Curvularia, and Alternaria species were seen with
      less frequency. Thus, it appears that Aspergillus may not be the most common
      etiologic agent in allergic "Aspergillus" sinusitis. Allergic fungal sinusitis is
      not unusual and its incidence may be increasing. On initial clinical evaluation
      it may be easily mistaken for malignancy or invasive fungal disease with the
      potential for overly aggressive treatment. Preoperative suspicion of allergic
      fungal sinusitis based on clinical and roentgenographic findings along with
      careful communication with the mycology laboratory about the possibility of
      dematiaceous fungal growth are necessary for proper diagnosis.

PMID- 1991059
TI  - Bacteriology of the ethmoid bullae in children with chronic sinusitis.
AB  - Cultures from 105 children with chronic sinusitis who had failed aggressive
      medical management were retrospectively studied. Patients with immunodeficiency
      and cystic fibrosis were excluded from the study. Because the most common sites
      of disease were the infundibula and anterior ethmoid sinuses, samples of mucosa
      removed from the anterior ethmoid bullae during endoscopic ethmoidectomy were
      routinely cultured for aerobic and anaerobic organisms. Fungal cultures were
      performed for 55 bullae. The principal organisms isolated were alpha-hemolytic
      Streptococcus, Staphylococcus aureus, Moraxella catarrhalis, Streptococcus
      pneumoniae, and Haemophilus influenzae non-type B. Only 12 anaerobic organisms
      and four fungi were isolated. Of the 204 bullae cultured, multiple organisms were
      found in 61 bullae and 40 showed no growth. Isolates of other less common
      organisms were also found. These data are analyzed on the basis of age and
      duration of symptoms, and antibiotic treatment is described.

PMID- 1991060
TI  - Quantitation of DNA ploidy in squamous intraepithelial neoplasia of the laryngeal
      glottis.
AB  - The DNA contents in 56 laryngeal glottic biopsy specimens with a spectrum of
      squamous intraepithelial neoplastic (SIN) changes were evaluated by image
      analysis. A combination of DNA histogram features were used to define abnormal
      DNA-containing cell populations that were interpreted as representing
      intraepithelial neoplastic transformation. Eighteen biopsy specimens were
      classified as dysplasia/keratosis and graded SIN I, six (33%) of which were
      aneuploid. Eighteen (78%) of 23 biopsy specimens graded SIN II were aneuploid,
      and all 15 biopsy specimens graded SIN III had abnormal quantities of nuclear
      DNA. Twelve biopsy specimens (six of SIN II grade and six of SIN III grade) were
      considered to represent keratinizing forms of dysplasia, and all 12 (100%) were
      found to contain increased (aneuploid) quantities of DNA. We conclude that the
      proposed SIN-grading scheme for laryngeal epithelial abnormalities exhibits
      strong correlations with nuclear DNA content. In addition, aneuploidy was
      observed in all SIN II- and SIN III-graded biopsy specimens with prominent
      keratinization.

PMID- 1991061
TI  - Histopathology of metastatic temporal bone tumors.
AB  - Temporal bone metastasis is now being reported with increasing frequency. To
      understand the process of temporal bone metastasis, complete histologic
      evaluation of the temporal bones is essential. In this study, 60 temporal bones
      from 33 patients were evaluated. Different patterns of temporal bone involvement
      were noted depending on the mode of spread to the temporal bone. Involvement of
      the temporal bone usually occurs late in the disease process and is often
      asymptomatic.

PMID- 1991062
TI  - Role of prophylactic antibiotics in uncontaminated neck dissections.
AB  - The use of perioperative prophylactic antibiotics in uncontaminated head and neck
      surgery remains controversial. We performed a retrospective analysis of 192
      patients undergoing uncontaminated neck dissections from 1976 to 1989. Wound
      infection developed in 10% (10/99) of patients who did not receive antibiotics,
      while only three (3.3%) of 93 patients who received antibiotics developed
      infections. This difference was not statistically significant. We correlated the
      use of flaps, length of surgery, prior radiation treatment, and postoperative
      complications with rate of wound infection. The difference was not statistically
      significant for any of these variables. Our beta error was, however, greater than
      0.2. Our data do not demonstrate efficacy of prophylactic antibiotics in
      uncontaminated neck dissections with statistical significance; however, a trend
      exists suggesting its possible value.

PMID- 1991063
TI  - Effectiveness of radiotherapy with radical neck dissection in cancers of the head
      and neck.
AB  - A retrospective analysis of 457 radical neck dissections performed over a 30-year
      period for cancers of the oral cavity, pharynx, and larynx was carried out. Two
      hundred thirteen patients underwent radiotherapy to the primary cancer site
      and/or to the neck. Of these, 164 underwent perioperative adjuvant radiotherapy
      and 24 underwent definitive radiation for cure and were followed up by salvage
      surgery. Thus, 188 patients received radiotherapy for nonrecurrent disease.
      Twenty-five additional patients underwent radiation for surgical failure
      following radical neck dissection. The goal of the study was to determine whether
      radiotherapy altered the course or end result of the disease. The T and N stage
      at onset of disease was similar for the radiotherapy and nonradiotherapy groups.
      Preoperative radiotherapy was effective in down staging the disease at the
      primary site and, to a lesser extent, in the lymph nodes, but had limited impact
      on survival. Failure to control the disease in the neck occurred in 60 (32%) of
      the 188 patients who received radiotherapy for primary disease; recurrence rates
      were lower in the combined therapy group than in the surgical group of patients
      with N2 and N3 stages of disease. The 3-year disease-free survival was 45%; this
      was no better than the 63% survival rate in patients who did not receive
      radiotherapy, although survival was better in the combined therapy group for
      patients with N3 stage of disease. The worst results were in those patients who
      were irradiated for surgical failure (14% survival); the 24 patients who required
      salvage radical neck dissection following failure of definitive radiotherapy for
      cure had a 42% survival.

PMID- 1991064
TI  - Scar revision.
AB  - Different scar revision techniques are compared on similar scars, all on the same
      patient. Comparison of the final results is unique and interesting and provides
      insight into choosing the "optimal" technique for these procedures. Historical
      perspective is provided.

PMID- 1991065
TI  - The characteristics of children with epiglottitis who develop the complication of
      pulmonary edema.
AB  - A review was performed of 234 consecutive cases of epiglottis that occurred
      during a 20-year period to delineate the rate of, and clinical characteristics
      associated with, the complication of pulmonary edema. As a result of the prior
      utilization of a "dual" management protocol, there were 170 children who received
      endotracheal intubation, and 64 children managed without placement of an
      artificial airway. In all, five children (2.1%) of varying ages developed this
      complication--all experienced severe airway obstruction progressing to
      respiratory arrest, with evidence of pulmonary edema developing shortly after
      endotracheal intubation. Two of these five children died due to complications
      resulting from upper airway obstruction-induced cardiorespiratory arrest. By
      contrast, no child with milder degrees of airway obstruction managed without an
      artificial airway exhibited clinical evidence of pulmonary edema. Several
      possible mechanisms for the development of this complication are described.
      Pulmonary edema associated with epiglottitis is an uncommon complication that can
      occur following endotracheal intubation in those patients with marked respiratory
      insufficiency. An artificial airway should be instituted in all cases of
      pediatric epiglottitis--the potential complication of pulmonary edema should be
      anticipated before placement of an artificial airway, especially in those
      patients with a severe degree of upper airway obstruction.

PMID- 1991066
TI  - Nasolacrimal obstruction after inferior meatus nasal antrostomy.
AB  - Transient epiphora following rhinoplasty or intranasal procedures is a common
      occurrence. Permanent nasolacrimal duct obstruction, however, is rare. This
      article documents four cases of nasolacrimal duct obstruction following
      intranasal antrostomy. Three patients were cured by dacryocystorhinostomy and a
      fourth refused surgery. The anatomy of the nasolacrimal duct in the inferior
      meatus has considerable variation. Although the duct typically opens in the
      inferior meatus immediately under the insertion of the inferior turbinate, the
      orifice can be a single hole, a slit, multiple holes, or a trough, and can be
      located anywhere from 30 to 40 mm dorsal to the anterior nares. We review the
      embryology and anatomy of the nasolacrimal orifice in the nose and make
      recommendations for safe surgery in the inferior meatus.

PMID- 1991067
TI  - Cranial base hemorrhage. A technique for controlling the uncontrollable.
AB  - In the management of trauma, control of life-threatening hemorrhage must be
      accomplished expeditiously if morbidity is to be decreased and mortality
      prevented. Hemorrhage from the inaccessible cranial base, especially when
      transected vessel stumps are not available for direct control, can be the most
      demanding, life-threatening, surgical emergency. We present our experience in
      utilizing an autologous bone grafting technique to successfully control severe
      hemorrhage from the base of the skull. In our review of the literature to date,
      we have been unable to ascertain whether this modality has been previously used.

PMID- 1991068
TI  - Riedel's thyroiditis.
AB  - Invasive fibrous (Riedel's) thyroiditis is a rare thyroid condition of unknown
      origin that may be associated with inflammatory fibrosclerosing processes
      elsewhere in the body. Although the condition is benign and self-limiting, its
      importance lies in its ability to clinically mimic carcinoma almost completely,
      necessitating performing an open biopsy to establish the correct diagnosis. In a
      review of over 700 thyroid operations performed at Loma Linda (Calif) University
      Medical Center in the past 15 years, we encountered only one documented case of
      Riedel's thyroiditis. Our patient presented with a firm thyroid mass, vocal cord
      paralysis, and symptoms of esophageal compression. Surgery was performed to
      obtain a definitive diagnosis and prevent the possibility of subsequent
      additional tracheal compression with airway compromise. The pathologic findings,
      as well as the medical and surgical treatment of this condition, are reviewed.

PMID- 1991069
TI  - Salivary gland involvement in Wegener's granulomatosis.
AB  - Salivary gland involvement is a rare clinical feature of Wegener's
      granulomatosis. We report a series of five cases in which submandibular or
      parotid gland swelling was part of the initial manifestation of the disease. All
      patients had limited forms of Wegener's granulomatosis. The value of
      determination of serum anti-neutrophil cytoplasmic autoantibodies is demonstrated
      in four of the cases, and its use as a new diagnostic adjunct and promising tool
      to monitor disease activity is discussed. The use of trimethoprim
      sulfamethoxazole as part of alternative treatment regimens for limited Wegener's
      granulomatosis is advocated.

PMID- 1991070
TI  - Pathologic quiz case 1. Castleman's disease, hyaline vascular type.

PMID- 1991071
TI  - Increased expression of pulmonary surfactant proteins in oxygen-exposed rats.
AB  - Exposure of adult rats to 85% ambient oxygen increased the content of surfactant
      proteins SP-A, SP-B, and SP-C recovered from alveolar lavage. The surfactant
      proteins increased during 1 to 7 d of oxygen exposure. The increased surfactant
      protein was associated with increased relative abundance of mRNA encoding each of
      the proteins in lung tissue. Exposure to hyperoxia progressively increased the
      amounts of the surfactant proteins in alveolar lavage fluid as estimated by
      immunoblot analysis after sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. The mRNAs encoding SP-A (1.7 and 1.0 kb), SP-B (1.6 kb), and SP
      C (0.9 kb) increased significantly after oxygen exposure for 5 d. The present
      findings support the concept that oxygen exposure mediates surfactant protein
      expression at a pretranslational level.

PMID- 1991072
TI  - Pulmonary calcitonin gene-related peptide immunoreactivity: nerve-endocrine cell
      interrelationships.
AB  - Respiratory epithelium has been reported to be supplied with sensory nerves and
      to contain irritant and other receptors. In this immunohistochemical study, we
      examined the incidence, morphology, and distribution of calcitonin gene-related
      peptide (CGRP) immunoreactivity in epithelial cells the rat respiratory tract,
      using peroxidase anti-peroxidase (PAP) techniques. CGRP immunoreactivity was
      localized in capsaicin-sensitive nerve fibers and in capsaicin-nonsensitive
      endocrine cells occurring singly or in groups. These CGRP-immunoreactive
      structures reached close to or actually touched the airway lumen, were widely and
      abundantly present in the respiratory epithelium, and were arranged in distinct
      and characteristic patterns. CGRP-immunoreactive nerves innervated not only
      grouped cells but also single cells, and the innervation of these cells differed
      depending on whether they were in extrapulmonary or intrapulmonary epithelium.
      The specificity of the immunoreactivity was confirmed by absorption tests that
      excluded cross-reactivity with other peptides. The results suggest that
      epithelial nerve fibers and endocrine-like cells exhibiting CGRP immunoreactivity
      form a morphologic, and probably also a functional, complex throughout the
      respiratory epithelium. CGRP innervation may be related to receptor functions of
      respiratory epithelium.

PMID- 1991074
TI  - Characterization of the cytochrome P-450 monooxygenase system in nonciliated
      bronchiolar epithelial (Clara) cells isolated from mouse lung.
AB  - The nonciliated bronchiolar epithelial (Clara) cell of the mouse is highly
      susceptible to toxicants that undergo metabolic activation, presumably because
      this cell type has high levels of cytochrome P-450 monooxygenases. As a first
      step in further defining the role of Clara cells in pulmonary xenobiotic
      activation and detoxication, we have isolated Clara cells (75 to 80% purity) and
      characterized them morphologically and biochemically. The identity of Clara
      cells, confirmed by transmission electron microscopy, was based on several
      features, including abundant agranular endoplasmic reticulum, large mitochondria,
      and dense secretory granules. Immunocytochemistry of isolated mouse cells showed
      that the majority were positive with antibodies against three major components of
      the pulmonary cytochrome P-450 monooxygenase system, cytochrome P-450 isozymes 2
      (IIB), 5 (IVB), and NADPH cytochrome P-450 reductase, purified from rabbit lung.
      The isolated cells also showed a positive reaction with an antibody against the
      cytochrome P-450 isozyme that is active in the stereoselective metabolism of
      naphthalene, cytochrome P-450 mN (mN). Immunocytochemistry using the antibody
      against cytochrome P-450 isozyme 6 (IA1), purified from rabbit lung, showed no
      reaction in the isolated cells. The presence of intact cytochrome P-450 protein
      was confirmed by sodium dodecyl sulfate polyacrylamide gel electrophoresis and
      Western blots of homogenates of isolated cell preparations. The N-demethylation
      of benzphetamine and epoxidation of naphthalene occurred at easily measurable
      rates in incubations of isolated Clara cells. In contrast, diols, quinones, and
      monohydroxylated benzo(a)pyrene metabolites, analyzed by high performance liquid
      chromatography, were undetectable in extracts of Clara cells incubated with 3H
      labeled substrate.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1991073
TI  - Potential regulation of inflammation in the lung by local metabolism of
      hydrocortisone.
AB  - Human lung tissue converts hydrocortisone to cortisone by the action of the
      enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD). Since cortisone is
      inactive as an antiinflammatory steroid, the action of this enzyme may regulate
      the local antiinflammatory effects of glucocorticoids in the lung. Minced human
      lung tissue (100 mg in 500 microliters medium) metabolized approximately 50% of
      added [3H]hydrocortisone within 2 h in most lung specimens. Metabolism was linear
      during this period and was found to occur over a broad range of concentrations of
      hydrocortisone (1 to 1,000 nM). Metabolism of hydrocortisone was not observed in
      minced pulmonary blood vessels or airways (2 to 3 mm), and pleura (containing
      some adherent parenchyma) had less activity than parenchyma. Cultured human
      tracheal epithelial cells metabolized hydrocortisone, while umbilical vein
      endothelial cells did not. Since glycyrrhizin, glycyrrhetinic acid, and
      carbenoxolone have antiinflammatory properties and have recently been shown to
      interfere with steroid metabolism in renal tissues, their effects on 11 beta-HSD
      in human lung tissue have been tested. Conversion of hydrocortisone to cortisone
      by lung tissue was inhibited by glycyrrhetinic acid (IC50, approximately 2.5 x
      10(-8) M) and carbenoxolone (1.5 x 10(-7) M), but not glycyrrhizin (greater than
      10(-5) M). It is proposed that inhibition of the metabolism of hydrocortisone by
      11 beta-HSD may partially explain the known antiinflammatory actions of orally
      administered glycyrrhetinic acid and carbenoxolone and that intrapulmonary
      administration of these compounds may produce antiinflammatory effects targeted
      to the lung.

PMID- 1991075
TI  - Elastin decreases the efficiency of neutrophil elastase inhibitors.
AB  - Elastase inhibitors are potential drugs for the control of lung emphysema. Since
      neutrophils may release elastase in the lung interstitium, elastin and inhibitors
      may complete locally for the binding of enzyme. To better evaluate the potential
      activity of antielastases, we have run experiments that mimic this in vivo
      competition. Elastase was added to mixtures of human lung elastin and inhibitor,
      and the solubilization of the fibrous substrate was measured as a function of
      time. Controls in which a synthetic substrate was used instead of elastin were
      run under identical conditions. We show that the rate constants for the
      irreversible inhibition of elastase by methoxysuccinyl-Ala2-Pro-Val
      chloromethylketone and L-657,229, a substituted beta lactam, are 28- and 63-fold
      lower with elastin than with a synthetic substrate, respectively. The rate
      constant decreases with increasing concentrations of elastin, indicating that the
      inhibition is competitive. Elastin also impairs the potency of the following
      reversible inhibitors: trifluoroacetyl-Lys-Ala-NH-C6H4-p-C6H11, trifluoroacetyl
      Lys-Ala-NH-C6H4-pN(C2H5)2, methoxysuccinyl-Ala2-Pro-Boro-Val-OH, and mucus
      proteinase inhibitor whose Ki values are 29- to 127-fold higher with elastin than
      with a synthetic substrate. Again the inhibition is competitive. We conclude that
      association rate constants of irreversible inhibitors and Ki values of reversible
      ones may be measured accurately using elastin as a substrate. The kinetic
      constants measured with elastin and not those determined with synthetic
      substrates should be used to decide whether a given inhibitor is potent enough to
      be a physiologic antielastase or a potential antielastase drug.

PMID- 1991076
TI  - Effect of epidermal growth factor on the fetal development of the
      tracheobronchial secretory apparatus in rhesus monkey.
AB  - Fetal rhesus monkeys were treated with recombinant human epidermal growth factor
      (EGF) to determine if EGF can induce maturation of the tracheobronchial secretory
      apparatus. At 75% of gestation, EGF was administered simultaneously into both the
      amniotic fluid and fetal abdominal cavity at an average dose of 66 micrograms/kg
      body weight, by each route over a 7-d period. At the end of the treatment period,
      the fetuses were delivered and either euthanized immediately or after maintenance
      on ventilatory support for 6 h. The lungs were removed, and the trachea and one
      lobe of the right lung was fixed and embedded for light microscopy. The left lung
      was lavaged with saline, and the collected fluid was used to quantify released
      secretory product. Secretory product was also measured in amniotic fluid as well
      as in situ on histologic sections of tracheal epithelium. When the tracheas of
      EGF-treated monkeys were examined, the epithelium was found to be taller and to
      contain a greater proportion of secretory cells and a smaller proportion of
      intermediate cells than the control group. However, there was no significant
      change in the total number of cells per millimeter of basal lamina or in the
      proportion of the epithelial population made up of basal or ciliated cells. There
      was more secretory product stored in the epithelium and submucosal glands and
      increased quantities of respiratory secretions in both lung lavage and amniotic
      fluid of EGF-treated monkeys.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1991077
TI  - Scientific abstracts. American Society of Regional Anesthesia annual meeting.
      Cincinnati, Ohio, April 4-7, 1991.

PMID- 1991078
TI  - Diabetic retinopathy and cataract surgery.

PMID- 1991079
TI  - Cotton-wool spots and retinal light sensitivity in diabetic retinopathy.
AB  - In 14 eyes of 14 patients with diabetic retinopathy the light sensitivity of
      retinal cotton-wool spots was studied by computerised perimetry, and the visual
      field data were accurately correlated with the corresponding morphology as seen
      on fundus photographs and fluorescein angiograms. In 12 of the eyes the
      examinations were repeated within one year in order to follow changes in retinal
      light sensitivity during the evolution of the lesions. Retinal cotton-wool spots
      were in all eyes associated with localised non-arcuate scotomata in the visual
      field. In four eyes the cotton-wool spots disappeared within three months of the
      first examination, and in two of these cases the corresponding scotomata
      disappeared together with the morphological lesions. In eight eyes the cotton
      wool spots (and the corresponding scotomata) had not resolved one year after the
      first examination. The mean blood pressure showed no significant difference
      between the patients in whom the lesions resolved within three months and the
      patients in whom the lesions persisted longer.

PMID- 1991080
TI  - Traumatic retinal detachment.
AB  - Seventy-seven patients developed retinal breaks following an episode of ocular
      contusion, and 65 (84.4%) of these developed rhegmatogenous retinal detachment.
      Surgical treatment successfully restored or maintained retinal apposition in 74
      (96.1%) of the eyes. Thirty-six (46.8%) eyes recovered visual acuity of 6/9 or
      better. Of the retinal breaks recognised dialysis at the ora serrata was observed
      in 49 eyes, of which 28 were situated at the lower temporal quadrant. Seventeen
      eyes had irregular breaks arising within necrotic retina at the site of scleral
      impact. Twenty-four (31.2%) patients had retinal break or retinal detachment
      diagnosed within 24 hours of injury and 49 (63.6%) within six weeks. Immediate
      retinal detachment was a feature of necrotic retinal breaks, while inferior oral
      dialyses led to a slow accumulation of subretinal fluid. Delayed diagnosis of
      retinal detachment was due either to opaque media or to failure to examine the
      retina after injury. Visual prognosis was good when retinal break or detachment
      were diagnosed within six weeks of injury. However, those patients who escaped
      initial retinal examination and were lost to follow-up had a less favourable
      visual outcome.

PMID- 1991081
TI  - Course of diabetic retinopathy following cataract surgery.
AB  - Five patients with mild to moderate retinopathy to both eyes underwent
      complication-free cataract surgery in one eye. Within three months of surgery
      deterioration of the retinopathy was observed in the operated eye only. In four
      patients there was an increase of intraretinal haemorrhages and hard exudates,
      accompanied by clinically significant macular oedema manifested as retinal
      thickening and extensive fluorescein leakage from both the macular and the
      peripapillary capillary networks. Of these four patients one also developed
      retinal ischaemia, evident ophthalmoscopically by flame-shaped haemorrhages and
      cotton-wool spots and angiographically by areas of capillary non-perfusion. The
      fifth patient showed proliferation of new blood vessels and vitreous haemorrhage.
      Diabetic patients scheduled for cataract surgery should undergo a thorough
      preoperative evaluation of any existing retinopathy. Postoperatively they should
      be followed up at close intervals so that any progression of retinopathy can be
      promptly detected and considered for laser treatment.

PMID- 1991082
TI  - Audit of an ophthalmology waiting list.
AB  - The hospital case notes of 209 (98%) of the 213 patients placed on an adult
      ophthalmic surgical waiting list between mid 1984 and mid 1985 were reviewed.
      Information on referral sources, previous eye surgery, outpatient visits, and
      treatment up to the end of 1987 was recorded. The vital status of patients up to
      the end of 1988 was also ascertained. Waiting list patients (123 women, 86 men)
      were elderly (73% over 65 years) and most (70%) were listed for cataract surgery.
      By the end of 1987 (30-42 months after waiting list entry) 64% of all patients
      (and 56% of cataract patients) had received surgery under the care of the health
      authority. The remainder had either died (12%), received surgery elsewhere (7%),
      were still on the waiting list (7%), no longer wanted or were unfit for surgery
      (6%), or had left the district (4%). By the end of 1988 (42-54 months after
      waiting list entry) 28% of the original waiting list population had died.

PMID- 1991083
TI  - Anisocoria in unilateral ophthalmic disease.
AB  - Pupillary diameters in the affected and unaffected eyes of 327 patients with
      uniocular red eye were assessed during fixation of a distant target. The mean
      pupillary diameters were similar in the unaffected eyes in each of eight
      diagnostic groups, but were significantly different (F = 3.84, p less than 0.001)
      in the diseased eyes. With corneal abrasions (p less than 0.001), marginal
      keratitis (p less than 0.05), and acute anterior uveitis (p less than 0.001) the
      mean pupillary diameter for the affected eye was significantly smaller than that
      of the unaffected eye. The observed differences of pupillary diameter probably
      reflect the role of neuronal and autocoid mechanisms in the unilateral control of
      pupillary size.

PMID- 1991084
TI  - Long-term efficacy of primary laser trabeculoplasty.
AB  - Sixty glaucomatous eyes of 60 patients treated with laser trabeculoplasty as
      primary therapy were reviewed retrospectively. There were 42 eyes with capsular
      glaucoma and 18 with simple glaucoma. The mean prelaser intraocular pressure
      (IOP) was 35.2 (SD = 6.5) mmHg. Success was defined as IOP less than or equal to
      22 mmHg without medication. The probability of success was 0.73 at 1 year, 0.66
      at 2 years, 0.57 at 3 years, and 0.50 at 4 years. Three eyes experienced
      progressive visual field loss or disc damage in spite of an intraocular pressure
      below 22 mmHg without medication. High prelaser pressure and the severity of the
      visual field defects were significant predictors of treatment failure.

PMID- 1991085
TI  - Mastering the infant donor eye: a new device for obtaining corneoscleral buttons
      for storage and corneal discs for keratoplasty.
AB  - The design and use of a new device for obtaining corneoscleral buttons for
      storage and corneal discs for keratoplasty from neonatal and adult donor eyes is
      described. The device is simple to use and eliminates most of the difficulties in
      handling infant donor eyes. It thus minimises the risk of damage to the corneal
      endothelium and the formation of stretch striae, which reduce the quality of the
      donor material for transplantation.

PMID- 1991086
TI  - Clinical evaluation of automated refraction in anterior chamber pseudophakia.
AB  - Automated refraction with the Canon RK-1 Autoref keratometer was evaluated in 85
      eyes of 85 patients with an anterior chamber intraocular lens implant and a best
      corrected visual acuity of at least 6/12. Autorefraction readings were obtained
      in 80 (94%) of these eyes. The agreement between autorefraction and clinical
      refraction data was 89% for spherical equivalence less than 0.51 dioptres (D),
      91% for sphere power less than 0.51 D, 82% for cylinder power less than 0.51 D,
      and 91% for cylinder axis less than 11 degrees. Autorefraction provides
      acceptably accurate postoperative refraction values in anterior chamber
      pseudophakia.

PMID- 1991087
TI  - Pupil cycle time and early autonomic involvement in ocular leprosy.
AB  - Ocular complications of leprosy patients often develop insidiously and with few
      if any symptoms. This study involves measurement of the pupil cycle time (PCT) to
      evaluate the autonomic nerve system of the iris to determine the presence of
      subclinical intraocular involvement. The study included 19 lepromatous (LL), 19
      borderline lepromatous (BL), and five borderline tuberculoid (BT) leprosy
      patients and involved 25 healthy volunteers, 10 patients with pulmonary
      tuberculosis and eight with Duhring disease. The PCT was measured in these
      groups. In all leprosy groups included in the study the PCT was higher than in
      the control groups. Moreover, the PCT of the leprosy patients without any
      intraocular involvement was higher than in the controls. These results show that
      in the ophthalmic examination of leprosy patients without any symptoms the fact
      that autonomic nerve system of the eye is affected by the leprosy can often be
      determined by measuring the PCT.

PMID- 1991089
TI  - Subretinal membranes of proliferative vitreoretinopathy.

PMID- 1991088
TI  - Electrophysiology and colour perimetry in dominant infantile optic atrophy.
AB  - A typical finding in dominant infantile optic atrophy (DIOA) is the variation of
      the phenotypic expression of the DIOA gene even within one family. It is of
      special interest for genetic consultation to evaluate an examination method for
      detecting subclinically involved patients. Seven patients of two families were
      examined. Three of them had the typical symptoms of DIOA: reduced visual acuity,
      tritan defect, temporal pallor of both optic discs, and a relative central
      scotoma for white test spots. In visual evoked cortical potentials (VECP) the
      amplitudes were reduced, and in one patient the latencies were slightly delayed
      and two patients considerably so. The amplitude of the negative component of the
      PERG was markedly reduced, while the positive component was normal. In the
      remaining four family members normal retinal and cortical responses were recorded
      under standard conditions and visual fields and colour vision (FM 100 hue) were
      also normal. However, static perimetry with blue test spots showed in two family
      members enlarged central scotomas, thus proving that they had subclinical DIOA.

PMID- 1991090
TI  - Post-traumatic hyperlipofuscinosis in the human retinal pigment epithelium.
AB  - Light microscopy (including fluorescence microscopy) and electron microscopy were
      applied to a study of the photoreceptor-retinal pigment epithelium (RPE) complex
      in a human eye which had been severely traumatised nine months prior to
      enucleation. The main feature of interest was a massive accumulation of
      lipofuscin in the retinal pigment epithelium at the posterior pole, and
      quantitative fluorescence microscopy provided values three times those obtained
      in appropriate control tissue. The photoreceptor layer was normal at the
      posterior pole but became progressively atrophic towards the periphery. The
      concentration of lipopofuscin was proportional to the degree of preservation of
      the retinal photoreceptors. By electron microscopy the cells in the RPE were seen
      to be packed with a mixture of lipofuscin granules and melanolysosomal complexes,
      but occasional photoreceptor phagosomes were found. Bruch's membrane and the
      choriocapillaris were normal. We attribute this hitherto unreported abnormality
      of the RPE after trauma to a dysfunction consequent on an overload of the
      monolayer by photoreceptor debris at the time of trauma.

PMID- 1991091
TI  - Decalcification of a choroidal osteoma.
AB  - A 56-year-old man presented with a clearly defined orange tumour in the posterior
      pole of his left eye. A choroidal osteoma was suspected, and ultrasonography
      confirmed the diagnosis. Fluorescein angiography demonstrated subretinal
      neovascularisation on the nasal edge of the tumour, which was treated with
      krypton laser photocoagulation twice. Recurrent subretinal neovascularisation
      occurred one year later and was not amenable to treatment. Three years after the
      patient first presented, thinning of the tumour was noted on follow-up
      examination. During the next 15 months the tumour completely disappeared, leaving
      an area of retinal pigment epithelial and choroidal atrophy. Total
      decalcification of the choroidal osteoma was demonstrated by ultrasonography.

PMID- 1991092
TI  - Anaphylactic reaction following application of chloramphenicol eye ointment.

PMID- 1991093
TI  - Eye surgery in Eritrea.

PMID- 1991095
TI  - Static and dynamic lipid asymmetry in cell membranes.

PMID- 1991094
TI  - Extracapsular cataract surgery with lens implantation in diabetics with and
      without proliferative retinopathy.
AB  - In a retrospective study we have examined all diabetics (66 operated eyes) and an
      equal number of non-diabetic matched controls who underwent extracapsular
      cataract extracation (ECCE) with intraocular lens (IOL) implantation over a two
      year period ending in December 1987. Of the diabetic patients' 76% eyes improved
      by at least two lines of Snellen acuity postoperatively. Of these patients 68%
      eyes and of the control eyes 83% achieved an acuity of 6/12 or better. In the
      diabetics the visual outcome depended on the state of the retinopathy and in
      particular the maculopathy. The diabetic group had a greater incidence of
      postoperative inflammation, but the major complications were related to
      continuing neovascularisation. Early postoperative laser photocoagulation may
      help to prevent these proliferative complications, and, provided a large,
      adequate capsulotomy is performed for capsular thickening, the presence of an IOL
      does not interfere with this photocoagulation. We also advise early postoperative
      assessment, and treatment if necessary, of any maculopathy. Diabetic retinopathy
      should no longer be regarded as a contraindication to intraocular lens insertion.

PMID- 1991096
TI  - Experimentally verifying molecular dynamics simulations through fluorescence
      anisotropy measurements.
AB  - The fluorescence anisotropy decay of the single tryptophan residue in
      phospholipase A2 was studied by use of differential polarized phase fluorometry
      and computer simulations of protein dynamics. The results enable the verification
      of a simulated dynamic event by direct experimental measurement on the same time
      scale. When all hydrogen atoms are modeled explicitly, the simulations agree well
      with the experimental measurements. However, the measurements contradict
      simulations in which nonpolar hydrogens are incorporated into "extended" or
      "united" atoms. These simulations predict an anisotropy decay in excess of
      measured values and appear to seriously underestimate the electrostatic
      interactions occurring between water and aromatic side chains. The results
      support the general validity of studying protein dynamics with the molecular
      mechanics approach and illustrate a potentially serious deficiency of simulations
      which do not explicitly model all hydrogen atoms.

PMID- 1991097
TI  - Conformation of thiocolchicine and two B-ring-modified analogues bound to tubulin
      studied with optical spectroscopy.
AB  - The interaction of tubulin with thiocolchicine and two thiocolchicine analogues,
      one lacking the B ring and one with a six-membered B ring, has been studied by
      using near-UV and CD spectroscopies. Rapid, reversible binding of the latter
      analogue to tubulin demonstrates the ability of the colchicine binding site to
      accommodate the phenyltropone system with a more coplanar conformation than is
      present in free colchicine. There is no evidence, however, that bound
      thiocolchicine should have a much less twisted conformation than free
      thiocolchicine. Thiocolchicine and the bicyclic analogue appear to have
      approximately the same conformation of the phenyltropone system, in both the free
      and the bound states, suggesting that this conformation has an optimal
      arrangement of the phenyl and tropone rings for binding to tubulin. In contrast
      to colchicine and related derivatives, the three thiocolchicine analogues show
      pronounced near-UV CD bands upon association to tubulin. No simple relation could
      be found between the sign pattern of the CD components in the near-UV band of the
      thiocolchicinoid chromophore and its axial chirality.

PMID- 1991099
TI  - Fluorescence and conformational stability studies of Staphylococcus nuclease and
      its mutants, including the less stable nuclease-concanavalin A hybrids.
AB  - We report steady-state and time-resolved fluorescence studies with the single
      tryptophan protein, Staphylococcus aureus A, and several of its site-directed
      mutants. A couple of these mutants, nuclease-conA and nuclease-conA-S28G (which
      are hybrid proteins containing a six amino acid beta-turn substitute from
      concanavalin A), are found to have a much lower thermodynamic stability than the
      wild type. The thermal transition temperatures for nuclease-conA and S28G are
      32.8 and 30.5 degrees C, which are about 20 degrees C lower than the Tm for wild
      type nuclease A. These mutant proteins also are denatured by a much lower
      concentration of the denaturants urea and guanidine hydrochloride. We also show
      that an unfolding transition in the structure of the nuclease-conA hybrids can be
      induced by relatively low hydrostatic pressure (approximately 700 bar). The free
      energy for unfolding of nuclease-conA (and nuclease-conA-S28G) is found to be
      only 1.4 kcal/mol (and 1.2 kcal/mol) by thermal, urea, guanidine hydrochloride,
      and pressure unfolding. Time-resolved fluorescence intensity and anisotropy
      measurements with nuclease-conA-S28G show the temperature-, urea-, and pressure
      perturbed states each to have a reduced average intensity decay time and to
      depolarize with a rotational correlation time of approximately 1.0 ns (as
      compared to a rotational correlation time of 11 ns for the native form of
      nuclease-conA-S28G at 20 degrees C).

PMID- 1991098
TI  - Small-angle X-ray scattering studies of calmodulin mutants with deletions in the
      linker region of the central helix indicate that the linker region retains a
      predominantly alpha-helical conformation.
AB  - Two mutant forms of calmodulin were examined by small-angle X-ray scattering in
      solution and compared with the wild-type protein. Each mutant has deletions in
      the linker region of the central helix: one lacks residues Glu-83 and Glu-84
      (Des2) and the other lacks residues Ser-81 through Glu-84 (Des4). The deletions
      change both the radii of gyration and the maximum dimensions of the molecules. In
      the presence of Ca2+, the observed radii of gyration are 22.4 A for wild-type
      bacterially expressed calmodulin, 19.5 A for Des2 calmodulin, and 20.3 A for Des4
      calmodulin. A reduction in the radius of gyration by 1-2 A on removal of calcium,
      previously observed in the native protein, was also found in the wild type and
      the Des4 mutant; however, no significant size change was observed in the Des2
      mutant. The large calcium-dependent conformational change in calmodulin induced
      by the binding of melittin [Kataoka, M., Head, J.F., Seaton, B.A., & Engelman,
      D.M. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 6944-6948] was observed in all the
      bacterially expressed proteins. Each protein appears to undergo a transition from
      a dumbbell shape to a more globular conformation on binding melittin in the
      presence of calcium, although quantitatively the changes in the wild-type and
      Des4 proteins greatly exceed those in Des2. Modeling shows the central linker
      region of the molecule. Thus, the structure of the linker region is stable enough
      to maintain the average orientation and separation of the lobes yet flexible
      enough to permit the lobes to approach each other upon binding a peptide.

PMID- 1991100
TI  - Neutron structure of subtilisin BPN': effects of chemical environment on hydrogen
      bonding geometries and the pattern of hydrogen-deuterium exchange in secondary
      structure elements.
AB  - The neutron structure of subtilisin BPN' has been refined and analyzed at 2.0-A
      resolution. The structure studied was a mutant variant of subtilisin, Met222---
      Gln, and was used because large, uninhibited crystals could be grown, which was
      not the case for the native molecule. Comparison of the structure with that of
      the native molecule indicated that the two structures are essentially the same.
      Using the capability of the neutron method to locate hydrogen and deuterium
      atoms, the protonation states of the six histidine residues were assigned. The
      active site histidine, His64, was found to be neutral at the pH of the analysis
      (pH 6.1). This group has an unexpectedly low pKa compared to assignments made by
      other techniques. The altered pKa of the group could result from electrostatic
      effects of other molecules in the crystal lattice. The dihedral conformations of
      a majority of the hydroxyl rotors were assigned. The preferred orientation was
      trans (180 degrees) with the other two low-energy conformers (60 degrees, 300
      degrees) about equally populated. For the serines, about 21% of the hydroxyls act
      exclusively as H-bond acceptors and 37% as H-bond donors, and in 42% the group
      functions as both. The experimentally observed dihedral conformations were
      compared to predicted conformations based on calculated energy criteria and
      showed a strong correspondence. Deviation from low-energy states could usually be
      explained by local electrostatic effects. The hydrogen exchange pattern of
      subtilisin identified the beta-sheet and alpha-helix secondary structure elements
      to be the most resistant to exchange. Fifty-five percent of the peptide amide
      hydrogens were fully exchanged, 15% unexchanged, and 30% partially exchanged. The
      largest concentration of unexchanged sites was in the seven-stranded parallel
      beta-sheet, in which there were 11 fully protected groups. Little correlation was
      found between H-bond length and angle and a peptide group's susceptibility toward
      exchange. Of the five alpha-helices the most protected from exchange is the one
      defined by residues 224-236. The pattern of exchange identifies regions in this
      helix where the H-bonding regularity is disrupted.

PMID- 1991102
TI  - Spectroscopic studies of myoglobin at low pH: heme structure and ligation.
AB  - We explore heme structure and ligation subsequent to a low-pH conformational
      transition in sperm whale myoglobin. Below pH 4.0, the iron-histidine bond breaks
      in metMb and deoxyMb. In MbCO, the majority of the iron-histidine bonds remain
      intact down to pH 2.6; however, the observation of a weak Fe-CO mode at 526 cm-1
      indicates that a small fraction of the sample has the histidine replaced by a
      weak ligand, possibly water. The existence of a sterically hindered CO
      subpopulation in MbCO and the continued association of the four-coordinate heme
      with the protein in deoxyMb suggest that the heme pocket remains at least
      partially intact in the acid-induced conformation. The global pH-dependent
      conformational change described here is clearly distinguished from the local
      "closed" to "open" transition described previously in MbCO [Morikis et al. (1989)
      Biochemistry 28, 4791-4800]. Further observations of the four-coordinate heme
      state yield insights on the mechanism of heme photoreduction and the assignment
      of the 760-nm band in deoxyMb.

PMID- 1991101
TI  - Identification of structural markers for vitamin B12 and other corrinoid
      derivatives in solution using FTIR spectroscopy.
AB  - The identification of structural markers for B12/protein interactions is crucial
      to a complete understanding of vitamin B12 transport and metabolic reaction
      mechanisms of B12 coenzymes. Fourier transform infrared spectroscopy can provide
      direct measurements of changes in the side chains and corrin ring resulting from
      B12/protein interactions. Using FTIR spectroscopy in various solvent systems, we
      have identified structural markers for corrinoids in the physiological state. We
      assign the major band (denoted B), which occurs at ca. 1630 cm-1 in D2O and ca.
      1675 cm-1 in ethanol, to the amide I C=O stretching mode of the propionamide side
      chains of the corrin ring. The lower frequency of band B in D2O versus ethanol is
      due to the greater hydrogen-bonding properties of D2O that stabilize the charged
      amide resonance form. Since the propionamides are known to be important in
      protein binding, band B is a suitable marker for monitoring the interaction of
      these side chains with proteins. We assign bands at ca. 1575 and 1545 cm-1
      (denoted C and D) as breathing modes of the corrin ring on the basis of the
      bands' solvent independence and their sensitivity to changes in axial ligation.
      As the sigma-donating strength of the axial ligands increases, the frequencies of
      bands C and D decrease, possibly indicating a lengthening of the corrin
      conjugated system. Band A, the known cyanide stretching frequency at ca. 2130 cm
      1, probes the cobalt-carbon distance in cyanocorrinoids. As the frequency of band
      A increases, the cobalt-carbon bond strength should decrease.

PMID- 1991103
TI  - Spectroscopic studies of myoglobin at low pH: heme ligation kinetics.
AB  - On the basis of the characterization of heme structure and ligation in
      equilibrium, we explore both proximal and distal ligation kinetics of myoglobin
      below pH 4. Upon photolysis of MbCO, a significant five-coordinate heme
      population is observed, with an intact iron-histidine bond that persists on the
      time scale of CO rebinding. Incomplete CO photolysis is attributed to a rapidly
      exchanging minority population of four-coordinate hemes, which leads to fast
      (greater than 10(10) s-1) geminate recombination. The possible relevance of such
      a mechanism at pH 7 is also noted. Using a novel experimental protocol, we
      observe the resonance Raman spectrum of partially photolyzed MbCO as a function
      of continuous wave illumination time (tau). Under extended illumination (tau
      approximately 35 ms at pH 3.4), there is a loss of intensity in the nu 4 region
      of the Raman spectrum and the iron-histidine mode is bleached from the spectrum
      of the five-coordinate photoproduct. In the Fe-CO stretching region of the CO
      bound fraction, the intensity of the 526-cm-1 mode increases with tau at the
      expense of the 491-cm-1 mode. These changes are interpreted as being due to
      replacement of the proximal histidine ligand under continuous illumination.
      Complete relaxation to the pure four-coordinate deoxy heme structure observed in
      equilibrium is not observed even as tau----infinity, presumably since CO
      rebinding leads to acidification of the iron and its complexation with histidine.
      We propose a kinetic model to account for our results and discuss the
      implications for previous low-pH kinetics measurements.

PMID- 1991105
TI  - Photoacoustic calorimetric study of the conversion of rhodopsin and isorhodopsin
      to lumirhodopsin.
AB  - The enthalpy and volume changes for the conversion of rhodopsin and isorhodopsin
      to lumirhodopsin have been investigated by time-resolved photoacoustic
      calorimetry. The conversion of rhodopsin to lumirhodopsin is endothermic by 3.9
      +/- 5.9 kcal/mol and is accompanied by an increase in volume of 29.1 +/- 0.8
      mL/mol. The lumirhodopsins produced from rhodopsin and isorhodopsin are
      energetically equivalent.

PMID- 1991104
TI  - Two-dimensional NMR and structure determination of salmon calcitonin in methanol.
AB  - The structure of the 32-residue peptide salmon calcitonin (sCT) in 90% MeOH-10%
      H2O has been investigated by two-dimensional NMR techniques and molecular
      modeling. Sequential assignments for nearly all of the 32 spin systems have been
      obtained, and results indicate that the heptaresidue loop formed by the disulfide
      bond between Cys-1 and Cys-7 is followed by an alpha-helical segment from Val-8
      through Tyr-22. A region of conformational heterogeneity is observed for residues
      20-25, resulting from the slow isomerism of the cis and trans forms of Pro-23.
      The C-terminal segment is found to exist in an extended conformation.

PMID- 1991106
TI  - Analysis of the conformation and stability of Escherichia coli derived
      recombinant human interleukin 4 by circular dichroism.
AB  - The conformation and stability of Escherichia coli derived recombinant human
      interleukin 4 (rhuIL-4) have been examined by circular dichroism (CD). Protein
      unfolding was detected by ellipticity changes at 222 nm with increasing
      concentrations of guanidine hydrochloride (GdnHCl). The unfolding midpoint
      ([GdnHCl]1/2) was 3.7 M, the free energy of unfolding, (delta GDH2O), was 5.9
      kcal/mol and the dependence of delta GD on the GdnHCl concentration (m) was 1.6
      (kcal/mol)/M. This unfolding was demonstrated to be reversible upon removal of
      the GdnHCl by dialysis. Analysis of the far-UV CD spectrum indicated the presence
      of a high percentage of alpha-helical structure (ca. 73%). A small change in
      ellipticity was noted over the pH range 1.9-9.6, suggesting that the protein
      undergoes a minor conformational change with an apparent pKa of 4.17. Virtually
      complete biological activity, measured in vitro in a T-cell proliferation assay,
      was recovered following exposure to extreme values of pH (i.e., pH 3 and 10). An
      analysis of the near-UV CD spectrum indicated that the single tryptophan residue
      at position 91 was unconstrained and most likely exposed to the solvent.
      Titration with 4,4'-dithiodipyridine and 2-nitrothiosulfobenzoate established
      that the six cysteine residues in rhuIL-4 were involved in intramolecular
      disulfide linkages. These data support that rhuIL-4 has a highly stable three
      dimensional structure.

PMID- 1991107
TI  - Scaffold-attached regions from the human interferon beta domain can be used to
      enhance the stable expression of genes under the control of various promoters.
AB  - We have transfected DNA corresponding to the complete chromatin domain of human
      interferon beta (huIFN-beta) gene into mouse L cells. In this construct, which is
      flanked by scaffold-attached regions (SARs), the gene's transcription was
      enhanced 20-30-fold with respect to DNAs containing only the immediate regulatory
      elements. To elucidate the role of SAR elements in the transcriptional
      enhancement, their position was varied relative to several artificial promoter
      gene combinations. It was found that SARs enhance general promoter functions in
      an orientation- and partially distance-independent manner; their effect is
      restricted to the integrated state of transfected templates. During the phase of
      transient expression, SAR elements were generally found to have an antagonizing
      effect.

PMID- 1991108
TI  - Chemical modifications and amino acid substitutions in recombinant hirudin that
      increase hirudin-thrombin affinity.
AB  - Recombinant hirudin (r-hirudin), unlike the naturally occurring leech protein,
      lacks a sulfate ester on Tyr-63 which reduces its binding affinity to thrombin by
      3-10-fold. We demonstrate that nitration or iodination of Tyr-63 restores hirudin
      thrombin affinity to levels similar to or exceeding that of the natural
      inhibitor. In contrast, nitration of Tyr-3 reduces the affinity of hirudin for
      thrombin. These chemical modifications results in multiple reaction products that
      are readily separated by reverse-phase HPLC. The mechanism of the observed
      changes in thrombin affinity may involve a reduction in the pK of the hydroxyl
      group of tyrosine due to substitution of the electrophilic iodo or nitro group on
      the phenyl ring, resulting in an increased negative charge at neutral pH. For Tyr
      63, this effect mimics the sulfatotyrosine of natural hirudin, leading to an
      increased thrombin affinity at the anion-binding exosite. For Tyr-3, the
      increased polarity may destabilize its interaction within the apolar-binding site
      of thrombin. Substitution of the highly conserved Tyr-3 residue with Phe or Trp
      not only enables specific and quantitative chemical modification at Tyr-63 but
      also independently increases hirudin-thrombin affinity. Kinetic analysis of
      thrombin inhibition showed that enhanced binding by r-hirudin(nitro-Tyr-63) is
      due to an increase in the association rate between hirudin and thrombin whereas
      the reduced binding of r-hirudin(nitro-Tyr-3) results from a large increase in
      the dissociation rate. These observations indicate that specific segments within
      both the amino- and carboxy-terminal regions of hirudin interact with thrombin.

PMID- 1991109
TI  - Kinetic analysis of lactose exchange in proteoliposomes reconstituted with
      purified lac permease.
AB  - Lactose exchange catalyzed by purified lac permease reconstituted into
      proteoliposomes was analyzed with unequal concentrations of lactose on either
      side of the membrane and at low pH so as to prevent equilibration of the two
      pools. Exchange with external concentrations below 1.0 mM is a single-exponential
      process, and the apparent affinity constants for external and internal substrate
      are close to the apparent KMs reported for active transport and efflux,
      respectively [Viitanen, P.V., Garcia, M. L., & Kaback, H. R. (1984) Proc. Natl.
      Acad. Sci. U.S.A. 81, 1629]. At external lactose concentrations above 1.0 mM, a
      second kinetic pathway becomes evident with an apparent affinity constant of
      about 6 mM which is similar to the apparent KM for facilitated influx. A second
      pathway is not observed with respect to internal lactose even when the
      concentration is increased up to 80 mM. Furthermore, high internal or external
      lactose concentrations do not inhibit the exchange reaction. Biphasic kinetics
      with respect to external lactose are retained in a mutant permease that catalyzes
      exchange but is defective in H(+)-coupled lactose transport. It is suggested that
      lac permease has more than one binding site and that this may be the underlying
      reason for the biphasic kinetics observed for both exchange and H(+)-coupled
      lactose transport.

PMID- 1991110
TI  - Role of proline residues in the structure and function of a membrane transport
      protein.
AB  - By use of site-directed mutagenesis, each prolyl residue in the lac permease of
      Escherichia coli at positions 28 (putative helix I), 31 (helix I), 61 (helix II),
      89 (helix III), 97 (helix III), 123 (helix IV), 192 (putative hydrophilic region
      7), 220 (helix VII), 280 (helix VIII), and 327 [helix X; Lolkema, J. S., et al.
      (1988) Biochemistry 27, 8307] was systematically replaced with Gly, Ala, or Leu
      or deleted by truncation of the C-terminus [i.e., Pro403 and Pro405; Roepe, P.D.,
      et al. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 3992]. Replacements were chosen
      on the basis of side-chain helical propensity: Gly, like Pro, is thought to be a
      "helix breaker", while Ala and Leu are "helix makers". With the exception of
      Pro28, each prolyl residue can be replaced with Gly or Ala, and Pro403 and -405
      can be deleted with the C-terminal tail, and significant lac permease activity is
      retained. In contrast, when Pro28 is replaced with Gly, Ala, or Ser, lactose
      transport is abolished, but permease with Ser28 binds p-nitrophenyl alpha-D
      galactopyranoside and catalyzes active transport of beta-galactopyranosyl-1-thio
      beta-D- galactopyranoside. Replacement of Pro28, -31, -123, -280, or -327 with
      Leu abolishes lactose transport, while replacement of Pro61, -89, -97, or -220
      with Leu has relatively minor effects. None of the alterations in permease
      activity is due to inability of the mutant proteins to insert into the membrane
      or to diminished lifetimes after insertion, since the concentration of each
      mutant permease in the membrane is comparable to that of wild-type permease as
      judged by immunological analyses.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1991111
TI  - Involvement of the protein-protein interactions in the thermodynamics of the
      electron-transfer process in the reaction centers from Rhodopseudomonas viridis.
AB  - Reaction centers from Rhodopseudomonas viridis were reconstituted into
      dimyristoylphosphatidylcholine (DMPC) and dielaidoylphosphatidylcholine (DEPC)
      liposomes. Freeze-fracture electron micrographs were performed on the samples
      frozen from temperatures above and below the phase transition temperatures of
      those lipids (Tc = 23 and 9.5 degrees C, in DMPC and DEPC, respectively). Above
      Tc, in the fluid conformation of the lipids, the reaction centers are randomly
      distributed in the vesicle membranes. Below Tc, aggregation of the proteins
      occurs. The Arrhenius plots of the rate constants of the charge recombination
      between P+ and QA- display a break at about 24 degrees C in DMPC vesicles and
      about 10 degrees C in DEPC vesicles (P represents the primary electron donor, a
      dimer of bacteriochlorophyll, and QA the primary quinone electron acceptor). This
      is in contrast to what was previously observed for the proteoliposomes of egg
      yolk phosphatidylcholine and for chromatophores [Baciou, L., Rivas, E., & Sebban,
      P. (1990) Biochemistry 29, 2966-2976], for which Arrhenius plots were linear. In
      DMPC and DEPC proteoliposomes, the activation parameters were very different on
      the two sides of Tc (delta H degrees for T less than Tc = 2.5 times delta H
      degrees for T greater than Tc), leading however, to the same delta G degrees
      values. Taking into account the structural and thermodynamic data, we suggest
      that, in vivo, protein-protein interactions play a role in the thermodynamic
      parameters associated with the energy stabilization process within the reaction
      centers.

PMID- 1991112
TI  - Solution structure of the basic region from the transcriptional activator GCN4.
AB  - The structure of the basic region (i.e., the region responsible for sequence
      specific binding to DNA) of the transcriptional activator GCN4 was studied. Two
      peptide fragments containing either the basic region alone (residues 240-280) or
      the basic and the dimerization leucine zipper domains (220-280) were synthesized
      and investigated by nuclear magnetic resonance and circular dichroic
      spectroscopy. The basic region in the absence of DNA appears as a mobile flexible
      segment folded into a loose helix. The helical stability increases upon addition
      of trifluoroethanol and/or lowering of the temperature. Dimerization via the
      leucine zipper does not affect the three-dimensional structure of the basic
      region. Possible consequences for the binding to DNA are discussed.

PMID- 1991114
TI  - NMR structural refinement of a tandem G.A mismatched decamer d(CCAAGATTGG)2 via
      the hybrid matrix procedure.
AB  - A complete relaxation matrix approach employing a matrix eigenvalue/eigenvector
      solution to the Bloch equations is used to evaluate the NMR solution structure of
      a tandemly positioned G.A double mismatch decamer oligodeoxyribonucleotide
      duplex, d(CCAAGATTGG)2. An iterative refinement method using a hybrid relaxation
      matrix combined with restrained molecular dynamics calculations is shown to
      provide structures having good agreement with the experimentally derived
      structures. Distances incorporated into the MD simulations have been calculated
      from the relaxation rate matrix evaluated from a hybrid NOESY volume matrix whose
      elements are obtained from the merging of experimental and calculated NOESY
      intensities. Starting from both A- and B-DNA and mismatch syn and anti models, it
      is possible to calculate structures that are in good atomic RMS agreement with
      each other (less than 1.6 A RMS) but differ from the reported crystal structure
      (greater than 3.6 A). Importantly, the hybrid matrix derived structures are in
      excellent agreement with the experimental solution conformation as determined by
      comparison of the 200-ms simulated and experimental NOESY spectra, while the
      crystallographic data provide spectra that are grossly different.

PMID- 1991113
TI  - Tryptophan fluorescence in electron-transfer flavoprotein:ubiquinone
      oxidoreductase: fluorescence quenching by a brominated pseudosubstrate.
AB  - We have studied the intrinsic fluorescence of the 12 tryptophan residues of
      electron-transfer flavoprotein:ubiquinone oxidoreductase (ETF:QO). The
      fluorescence emission spectrum (lambda ex 295 nm) showed that the fluorescence is
      due to the tryptophan residues and that the contribution of the 22 tyrosine
      residues is minor. The emission maximum (lambda m 334 nm) and the bandwidth
      (delta lambda 1/2 56 nm) suggest that the tryptophans lie in hydrophobic
      environments in the oxidized protein. Further, these tryptophans are inaccessible
      to a range of ionic and nonionic collisional quenching agents, indicating that
      they are buried in the protein. Enzymatic or chemical reduction of ETF:QO results
      in a 5% increase in fluorescence with no change of lambda m or delta lambda 1/2.
      This change is reversible upon reoxidation and is likely to reflect a
      conformational change in the protein. The ubiquinone analogue Q0(CH2)10Br, a
      pseudosubstrate of ETF:QO (Km = 2.6 microM; kcat = 210 s-1), specifically
      quenches the fluorescence of one tryptophan residue (Kd = 1.6-3.2 microM) in
      equilibrium fluorescence titrations. The ubiquinone homologue UQ-2 (Km = 2
      microM; kcat = 162 s-1) and the analogue Q0(CH2)10OH (Km = 2 microM; kcat = 132 s
      1) do not quench tryptophan fluorescence; thus the brominated analogue acts as a
      static heavy atom quencher. We also describe a rapid purification for ETF:QO
      based on extraction of liver submitochondrial particles with Triton X-100 and
      three chromatographic steps, which results in yields 3 times higher than
      previously published methods.

PMID- 1991115
TI  - Effects of bulge composition and flanking sequence on the kinking of DNA by
      bulged bases.
AB  - We recently showed that bulged bases kink duplex DNA, with the degree of kinking
      increasing in roughly equal increments as the number of bases in the bulge
      increases from one to four [Hsieh, C.-H., & Griffith, J.D. (1989) Proc. Natl.
      Acad. Sci. U.S.A. 86, 4833-4837]. Here we have examined the kinking of DNA by
      single A, C, G, or T bulges with different neighboring base pairs. Synthetic 30
      base pair (bp) duplex DNAs containing 2 single-base bulges spaced by 10 bp were
      ligated head to tail, and their electrophoretic behavior in highly cross-linked
      gels was examined. All bulge-containing DNAs showed marked electrophoretic
      retardations as compared to non-bulge-containing DNA. Regardless of the sequence
      of the flanking base pairs, purine bulges produced greater retardations than
      pyrimidine bulges. Furthermore, C and T bulges produced the same retardations as
      did G and A bulges. Bulged DNA containing different flanking base pairs showed
      marked differences in electrophoretic mobility. For C-bulged DNA, the greatest
      retardations were observed with G.C neighbors, the least with T.A neighbors, and
      an intermediate amount with a mixture of neighboring base pairs. For A-bulged
      DNA, the retardations were greatest with G.C neighbors, less with T.A neighbors,
      even less with a mixture of neighboring base pairs, and finally least with C.G
      neighbors. Thus flanking base pairs affect C-bulged DNA and A-bulged DNA
      differently, and G.C and C.G flanking base pairs were seen to have very different
      effects. These results imply an important role of base stacking in determining
      how neighboring base pairs influence the kinking of DNA by a single-base bulge.

PMID- 1991116
TI  - DNA-nogalamycin interactions.
AB  - The anthracycline antibiotic nogalamycin differs from the more common daunomycin
      type anthracyclines by substitution on both ends of the intercalating
      chromophore, giving nogalamycin the approximate shape of a dumbbell. The
      chromophore of daunomycin is substituted on only one end. In nogalamycin, the
      positively charged amino sugar substituent of daunomycin is replaced by an
      uncharged nogalose sugar and a methyl ester group. The other end of nogalamycin,
      where daunomycin is unsubstituted, is fused to a bicyclo amino sugar with a
      positively charged dimethylamino group. Much larger DNA fluctuations are required
      for intercalative entry of nogalamycin than for entry of daunomycin. This report
      describes the X-ray crystal structure of the complex between nogalamycin and the
      self-complementary DNA hexamer d(me5CGTsAme5CG). The DNA contains cytosines
      methylated at the 5-positions and a phosphorothioate linkage at the TpA step.
      Nogalamycin intercalates at the terminal CpG steps and interacts with both
      strands in both grooves of the DNA. Large conformational adjustments in both
      nogalamycin and the DNA are necessary to form a stable, intercalative complex.
      The interactions of the bases with the nogalamycin substituents lead to sliding
      of bases relative to each other along the normal to Watson-Crick hydrogen bonds.
      The planarities of base pairs surrounding the intercalation site are distorted.
      The backbones of the two strands are distorted asymmetrically by nogalamycin with
      large deviations from standard B-DNA geometry. The complex between nogalamycin
      and DNA illustrates the conformational flexibility of DNA. The hydrogen-bonding
      interactions between nogalamycin and DNA do not suggest a sequence-specific
      binding of the drug, although additional secondary effects might lead to
      differences between various intercalation sites.

PMID- 1991117
TI  - Interaction of berenil with the EcoRI dodecamer d(CGCGAATTCGCG)2 in solution
      studied by NMR.
AB  - The conformation of the EcoRI dodecamer d(CGCGAATTCGCG)2 has been examined in
      solution by 1H and 31P NMR. Spin-spin coupling constants and nuclear Overhauser
      (NOE) enhancement spectroscopy show that all deoxyriboses lie in the south
      domain, with a small admixture of the north conformation (0-20%). The time
      dependence of the nuclear Overhauser enhancements also reveals a relatively
      uniform conformation at the glycosidic bonds (average angle, chi = -114 degrees).
      The average helical twist is 36.5 degrees (9.8 base pairs per turn). Tilt angles
      are small (in the range 0 to -10 degrees), and roll angles are poorly determined.
      Unlike single-crystal X-ray studies of the same sequence, there is no evidence
      for asymmetry in the structure. Both the NOE intensities and 31P relaxation data
      imply conformational anomalies at the C3-G4/C9-G10 and the A5-A6/T7-T8 steps.
      Berenil binds in 1:1 stoichiometry to the dodecamer with high affinity (Kd = 1
      microM at 298 K) and causes substantial changes in chemical shifts of the sugar
      protons of nucleotides Ado 5-Cyt 9 and of the H2 resonances of the two Ado
      residues. No significant asymmetry appears to be induced in the DNA conformation
      on binding, and there is no evidence for intercalation, although the binding site
      is not centrosymmetric. NOEs are observed between the aromatic protons of berenil
      and the H1' of both Thy 7 and Thy 8, as well as to Ado 5 and Ado 6 H2. These
      results firmly establish that berenil binds via the minor groove and closely
      approaches the nucleotides Ado 6, Thy 7, and Thy 8. On the basis of quantitative
      NOE spectroscopy and measurements of spin-spin coupling constants, changes in the
      conformations of the nucleotides are found to be small. Using the observed NOEs
      between the ligand and the DNA together with the derived glycosidic torsion
      angles, we have built models that satisfy all of the available solution data. The
      berenil molecule binds at the 5'-AAT (identical to 5'-ATT on the complementary
      strand) site such that (i) favorable hydrogen bonds are formed between the
      charged amidinium groups and the N3 atoms of Ado 6 and Ado 18 and (ii) the ligand
      is closely isohelical with the floor of the minor groove.

PMID- 1991118
TI  - Kinetic analysis of protein kinase C: product and dead-end inhibition studies
      using ADP, poly(L-lysine), nonhydrolyzable ATP analogues, and diadenosine
      oligophosphates.
AB  - The kinetic mechanism of protein kinase C (PKC) was analyzed via inhibition
      studies using the product MgADP, the nonhydrolyzable ATP analogue adenosine 5'
      (beta,gamma-imidotriphosphate) (MgAMPPNP), the peptide antagonist poly(L-lysine),
      and several naturally occurring ATP analogues that are produced in rapidly
      growing cells, i.e., the diadenosine oligophosphates (general structure: ApnA; n
      = 2-5). By use of histone as the phosphate acceptor, the inhibition of PKC by
      MgAMPPNP and MgADP was found to be competitive vs MgATP (suggesting that these
      compounds bind to the same enzyme form), whereas their inhibition vs histone was
      observed to be noncompetitive. In contrast, the inhibition by poly(L-lysine)
      appeared competitive vs histone but uncompetitive vs MgATP, which is consistent
      with a model wherein MgATP binding promotes the binding of poly(L-lysine) or
      histone. With the diadenosine oligophosphates, the degree of PKC inhibition was
      found to increase according to the number of intervening phosphates. The
      diadenosine oligophosphates Ap4A and Ap5A were the most effective antagonists of
      PKC, with Ap5A being approximately as potent as MgADP and MgAMPPNP. However, as
      opposed to MgADP and MgAMPPNP, Ap4A and Ap5A appear to act as noncompetitive
      inhibitors vs both MgATP and histone, suggesting that they can interact at
      several points in the reaction pathway. These studies support the concept of a
      steady-state mechanism where MgATP binding preferentially precedes that of
      histone, followed by the release of phosphorylated substrate and MgADP.
      Furthermore, these results indicate a differential interaction of the diadenosine
      oligophosphates with PKC, when compared to other adenosine nucleotides.

PMID- 1991119
TI  - Steady-state and pre-steady-state kinetics of propionaldehyde oxidation by sheep
      liver cytosolic aldehyde dehydrogenase at pH 5.2. Evidence that the release of
      NADH remains rate-limiting in the enzyme mechanism at acid pH values.
AB  - The kcat value for the oxidation of propionaldehyde by sheep liver cytosolic
      aldehyde dehydrogenase increased 3-fold, from 0.16 s-1 at pH 7.6 to 0.49 s-1 at
      pH 5.2, in parallel with the increase in the rate of displacement of NADH from
      binary enzyme.NADH complexes. A burst in nucleotide fluorescence was observed at
      all pH values consistent with the rate of isomerization of binary enzyme.NADH
      complexes constituting the rate-limiting step in the steady state. No substrate
      activation by propionaldehyde was observed at pH 5.2, but the enzyme exhibited
      dissociation/association behavior. The inactive dissociated form of the enzyme
      was favored by low enzyme concentration, low pH, and low ionic strength.
      Propionaldehyde protected the enzyme against dissociation.

PMID- 1991120
TI  - Cooperativity of papain-substrate interaction energies in the S2 to S2' subsites.
AB  - Enzyme-substrate contacts in the hydrolysis of ester substrates by the cysteine
      protease papain were investigated by systematically altering backbone hydrogen
      bonding and side-chain hydrophobic contacts in the substrate and determining each
      substrate's kinetic constants. The observed specificity energies [defined as
      delta delta G obs = -RT ln [(kcat/KM)first/(kcat/KM)second)]] of the substrate
      backbone hydrogen bonds were -2.7 kcal/mol for the P2 NH and -2.6 kcal/mol for
      the P1 NH when compared against substrates containing esters at those sites. The
      observed binding energies were -4.0 kcal/mol for the P2 Phe side chain, -1.0
      kcal/mol for the P1' C=O, and -2.3 kcal/mol for the P2' NH. The latter three
      values probably all significantly underestimate the incremental binding energies.
      The P2 NH, P2 Phe side-chain, and P1 NH contacts display a strong
      interdependence, or cooperativity, of interaction energies that is characteristic
      of enzyme-substrate interactions. This interdependence arises largely from the
      entropic cost of forming the enzyme-substrate transition state. As favorable
      contacts are added successively to a substrate, the entropic penalty associated
      with each decreases and the free energy expressed approaches the incremental
      interaction energy. This is the first report of a graded cooperative effect.
      Elucidation of favorable enzyme-substrate contacts remote from the catalytic site
      will assist in the design of highly specific cysteine protease inhibitors.

PMID- 1991122
TI  - Reassessment of the catalytic mechanism of glycogen debranching enzyme.
AB  - The amylo-1,6-glucosidase catalytic activity of glycogen debranching enzyme
      allows it to hydrolyze alpha-D-glucosyl fluoride, in the absence or presence of
      glycogen or oligosaccharides, releasing equal amounts of fluoride and glucose at
      rates comparable to those seen with the natural substrates. 2-Deoxy-2-fluoro
      alpha-D-glucosyl fluoride is found to be a poor substrate, rather than the
      covalent inhibitor that would be expected for a glucosidase which catalyzes
      hydrolysis of the glycosidic linkage with retention of anomeric configuration. In
      fact, analysis of the glucosidase reaction by NMR reveals that the debranching
      enzyme hydrolyzes the glycosidic linkage with inversion of configuration,
      releasing beta-D-glucose from both alpha-glucosyl fluoride and its natural
      substrate, the phosphorylase limit dextrin. In contrast, its transferase activity
      necessarily proceeds with retention of configuration. As has been seen with other
      "inverting" glycosidases, the debranching enzyme releases beta-D-glucose from
      beta-D-glucosyl fluoride in the presence of oligosaccharides such as maltohexaose
      and cyclomaltoheptaose but, unlike the others, not in their absence. An
      intermediate glucosyl-alpha-(1,6)-cyclomaltoheptaose has been detected by NMR
      analysis. In the presence of a water-soluble carbodiimide, a single mole of
      glycine ethyl ester is incorporated into each mole of the debranching enzyme,
      resulting in its inactivation when measured by the combined assay for both
      transferase and glucosidase activities. Measurement of the latter two activities
      independently indicates that it is the transferase activity which is inactivated,
      while the glucosidase activity, measured with alpha-D-glucosyl fluoride as
      substrate, is unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1991121
TI  - NMR structural studies of the ionizing radiation adduct 7-hydro-8
      oxodeoxyguanosine (8-oxo-7H-dG) opposite deoxyadenosine in a DNA duplex. 8-Oxo-7H
      dG(syn).dA(anti) alignment at lesion site.
AB  - Proton NMR studies are reported on the complementary d(C1-C2-A3-C4-T5-A6-oxo-G7
      T8-C9-A10-C11-C12).d(G13-G14-T15- G16-A17-A18-T19- A20-G21-T22-G23-G24)
      dodecanucleotide duplex (designated 8-oxo-7H-dG.dA 12-mer), which contains a
      centrally located 7-hydro-8-oxodeoxyguanosine (8-oxo-7H-dG) residue, a group
      commonly found in DNA that has been exposed to ionizing radiation or oxidizing
      free radicals. From the NMR spectra it can be deduced that this moiety exists as
      two tautomers, or gives rise to two DNA conformations, that are in equilibrium
      and that exchange slowly. The present study focuses on the major component of the
      equilibrium that originates in the 6,8-dioxo tautomer of 8-oxo-7H-dG. We have
      assigned the exchangeable NH1, NH7, and NH2-2 base protons located on the Watson
      Crick and Hoogsteen edges of 8-oxo-7H-dG7 in the 8-oxo-7H-dG.dA 12-mer duplex,
      using an analysis of one- and two-dimensional nuclear Overhauser enhancement
      (NOE) data in H2O solution. The observed NOEs derived from the NH7 proton of 8
      oxo-7H-dG7 to the H2 and NH2-6 protons of dA18 establish an 8-oxo-7H-dG7(syn).dA
      18(anti) alignment at the lesion site in the 8-oxo-7H-dG.dA 12-mer duplex in
      solution. This alignment, which places the 8-oxo group in the minor groove, was
      further characterized by an analysis of the NOESY spectrum of the 8-oxo-7H-dG.dA
      12-mer duplex in D2O solution. We were able to detect a set of intra- and
      interstrand NOEs between protons (exchangeable and nonexchangeable) on adjacent
      residues in the d(A6-oxo-G7-T8).d(A17-A18-T19) trinucleotide segment centered
      about the lesion site that establishes stacking of the oxo-dG7(syn).dA(anti) pair
      between stable Watson-Crick dA6.dT19 and dT8.dA17 base pairs with minimal
      perturbation of the helix. Thus, both strands of the 8-oxo-7H-dG.dA 12-mer duplex
      adopt right-handed conformations at and adjacent to the lesion site, the
      unmodified bases adopt anti glycosidic torsion angles, and the bases are stacked
      into the helix. The energy-minimized conformation of the central d(A6-oxo-G7
      T8).d(A17-A18-T19) segment requires that the 8-oxo-7H-dG7(syn).dA18(anti)
      alignment be stabilized by two hydrogen bonds from NH7 and O6 of 8-oxo-7H
      dG7(syn) to N1 and NH2-6 of dA18(anti), respectively, at the lesion
      site.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1991123
TI  - Second-site revertants of an inactive T4 lysozyme mutant restore activity by
      restructuring the active site cleft.
AB  - Substitution of Thr26 by Gln in the lysozyme of bacteriophage T4 produces an
      enzyme with greatly reduced activity but essentially unaltered stability relative
      to wild type. Spontaneous second-site revertants of the mutant were selected
      genetically; two of them were chosen for structural and biochemical
      characterization. One revertant bears (in addition to the primary mutation) the
      substitution Tyr18----His, the other, Tyr18----Asp. The primary mutant and both
      revertant lysozyme genes were reconstructed in a plasmid-based expression system,
      and the proteins were produced and purified. The two revertant lysozymes exhibit
      enzymatic activities intermediate between wild type and the primary mutant; both
      also exhibit melting temperatures approximately 3 degrees C lower than either the
      wild type or the primary mutant. Crystals suitable for X-ray diffraction analysis
      were obtained from both revertant lysozymes, but not the primary mutant.
      Structures of the double mutant lysozymes were refined at 1.8-A resolution to
      crystallographic residuals of 15.1% (Tyr18----His) and 15.2% (Tyr18----Asp).
      Model building suggests that the side chain of Gln26 in the primary mutant is
      forced to protrude into the active site cleft, resulting in low catalytic
      activity. In contrast, the crystal structures of the revertants reveal that the
      double substitutions (Gln26 and His18, or Gln26 and Asp18) fit into the same
      space that is occupied by Thr26 and Tyr18 in the wild-type enzyme; the effect is
      a restructuring of the surface of the active site cleft, with essentially no
      perturbation of the polypeptide backbone. This restructuring is effected by a
      novel series of hydrogen bonds and electrostatic interactions that apparently
      stabilize the revertant structures.

PMID- 1991124
TI  - Role of the conserved active site residue tryptophan-24 of human dihydrofolate
      reductase as revealed by mutagenesis.
AB  - The active sites of all bacterial and vertebrate dihydrofolate reductases that
      have been examined have a tryptophan residue near the binding sites for NADPH and
      dihydrofolate. In cases where the three-dimensional structure has been determined
      by X-ray crystallography, this conserved tryptophan residue makes hydrophobic and
      van der Waals interactions with the nicotinamide moiety of bound NADPH, and its
      indole nitrogen interacts with the C4 oxygen of bound folate through a bridge
      provided by a bound water molecule. We have addressed the question of why even
      the very conservative replacement of this tryptophan by phenylalanine does not
      seem to occur naturally. Human dihydrofolate reductase with this replacement of
      tryptophan by phenylalanine has increased rate constants for dissociation of
      substrates and products and a considerably decreased rate of hydride transfer.
      These cause some changes in steady-state kinetic behavior, including substantial
      increases in Michaelis constants for NADPH and dihydrofolate, but there is also a
      3-fold increase in kcat. The branched mechanistic pathway for this enzyme has
      been completely defined and is sufficiently different from that of wild-type
      enzyme to cause changes in some transient-state kinetics. The most critical
      changes resulting from the amino acid substitution appear to be a 50% decrease in
      stability and a decrease in efficiency from 69% to 21% under intracellular
      conditions.

PMID- 1991126
TI  - Purification and properties of a subtilisin inhibitor and an associated trypsin
      inhibitor from Dolichos biflorus.
AB  - A subtilisin inhibitor and an associated trypsin inhibitor from Dolichos biflorus
      were purified to homogeneity by conventional methods such as chromatography on
      DEAE-cellulose, gel filtration on Sephadex G-75, PAGE and affinity
      chromatography. The final preparations were homogeneous on PAGE. Their pI were
      7.66 and 7.70, respectively. The dissociation constant of the complex of the
      inhibitor with subtilisin was 2.69.10(-10) M. Both the inhibitors were stable to
      heat, TCA and ethanol. The molecular weights of the subtilisin inhibitor and the
      associated trypsin inhibitor by gel filtration were 7500 and 8200, respectively.

PMID- 1991125
TI  - Mechanism of DNA replication fidelity for three mutants of DNA polymerase I:
      Klenow fragment KF(exo+), KF(polA5), and KF(exo-).
AB  - Inhibition of the pre-steady-state burst of nucleotide incorporation by a single
      incorrect nucleotide (nucleotide discrimination) was measured with the Klenow
      fragment of DNA polymerase I [KF(exo+)]. For the eight mispairs studied on three
      DNA sequences, only low levels of discrimination ranging from none to 23-fold
      were found. The kinetics of dNTP incorporation into the 9/20-mer at low
      nucleotide concentrations was also determined. A limit of greater than or equal
      to 250 s-1 was placed on the nucleotide off-rate from the KF(exo+)-9/20-dTTP
      complex in accord with nucleotide binding being at equilibrium in the overall
      kinetic sequence. The influence of the relatively short length of the 9/20-mer on
      the mechanism of DNA replication fidelity was determined by remeasuring important
      kinetic parameters on a 30/M13-mer with high homology to the 9/20-mer. Pre-steady
      state data on the nucleotide turnover rates, the dATP(alpha S) elemental effect,
      and the burst of dAMP misincorporation into the 30/M13-mer demonstrated that the
      kinetics were not affected by the length of the DNA primer/template. The effects
      on fidelity of two site-specific mutations, KF(polA5) and KF(exo-), were also
      examined. KF(polA5) showed an increased rate of DNA dissociation and a decreased
      rate of polymerization resulting in less processive DNA synthesis. Nevertheless,
      with at least one misincorporation event, that of dAMP into the 9/20-mer,
      KF(polA5) displays an increased replication fidelity.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1991127
TI  - Purification and characterization of a veratryl alcohol oxidase enzyme from the
      lignin degrading basidiomycete Pleurotus ostreatus.
AB  - A veratryl alcohol oxidase (VAO) enzyme was discovered in cultures of Pleurotus
      ostreatus. The enzyme, which oxidizes veratryl alcohol to veratraldehyde reducing
      O2 to H2O2, was purified to homogeneity and its main structural and catalytic
      properties have been determined. The enzyme is a glycoprotein and contains FAD as
      a prosthetic group. The amino acid composition and carboxy- and amino-terminal
      sequences were determined. Primary aromatic alcohols with methoxy substituents in
      position four are good substrates for VAO; cinnamyl alcohol is the substrate
      which is oxidized faster whereas coniferyl alcohol is oxidized at a slower rate.
      The enzyme is moderately thermostable (t1/2(55 degrees C) about 1.5 h, apparent
      melting temperature about 60 degrees C). The enzyme stability in 50%
      water/organic solvents mixtures has also been studied.

PMID- 1991128
TI  - Physicochemical characteristics of the terbium-adriamycin complex and its effects
      on the sinus node automaticity.
AB  - The physicochemical characteristics of the terbium-adriamycin complex
      (terbomycin) were studied. Perturbations in the visible absorption spectrum of
      adriamycin by terbium (Tb3+) was indicative of formation of the terbomycin
      complex. The absorption maximum of free adriamycin at 479 nm shifted towards the
      absorption maximum of terbomycin at 539 nm. The binding of Tb3+ to adriamycin was
      negligible at acidic pH. At alkaline pH, the affinity of Tb3+ for adriamycin
      increased. The stoichiometry of binding was estimated to be 0.5; one Tb3+ ion per
      two adriamycin molecules. Thermodynamic analysis revealed that the spontaneous
      formation of terbomycin was due to an increase in the entropy of the system. The
      effects of adriamycin, Tb3+ and terbomycin on sinus node automaticity were
      studied using sinus node from rats, superfused with modified mammalian Tris
      Tyrode's solution (37 degrees C). The sinus node rate was monitored with
      intracellular microelectrodes. 25 microM Tb3+ increased the sinus node rate.
      Adriamycin (50 microM) depressed sinus node automaticity. Terbomycin also reduced
      the sinus node rate. There was no difference between the effects of adriamycin
      and terbomycin. The chronotropic effect of terbomycin persisted in the presence
      of atropine.

PMID- 1991129
TI  - The effect of hydrophobic interaction on endotoxin adsorption by polymeric
      affinity matrix.
AB  - Endotoxin, a major pyrogen of concern to the biological industry, is a
      lipopolysaccharide containing a highly hydrophobic region, lipid A, in its
      structure. The effect of hydrophobic interaction on endotoxin adsorption from an
      aqueous solution was studied by covalently bonding aminoalkyl groups with varying
      hydrocarbon lengths to a cellulose and acrylic composite matrix. The amount of
      endotoxin adsorbed on the matrix increased with the increasing length of alkyl
      groups, demonstrating the contribution of hydrophobic interaction between
      endotoxin and the solid matrix. Both the hydrophobic and the charge interaction
      prove to be effective for endotoxin adsorption, and a synergistic effect from the
      dual chemical forces is achievable under specified conditions. The effect of
      solvent, pH and salts on endotoxin adsorption provides further evidence for the
      importance of hydrophobic force as a means of removing endotoxin from aqueous
      solutions.

PMID- 1991130
TI  - Species-specific distribution of cathepsin E in mammalian blood cells.
AB  - The distribution of cathepsins D and E in leukocytes and erythrocyte ghosts of
      several mammalian species, and in HL-60 and K-562 cells was examined by means of
      a combined application of electrophoretic and immunochemical methods. Cathepsin D
      was found in leukocytes of all species examined, but the distribution of
      cathepsin E was found to be species-specific: pigs, cows and goats had no
      cathepsin E activity in leukocytes or erythrocytes at all. In humans, cathepsin E
      occurred in erythrocytes but not in leukocytes, which contrasted with the guinea
      pig pattern of its presence in leukocytes and its absence in erythrocytes. No
      cathepsin E-related enzymes were found in HL-60 or K-562 cells, but these human
      leukemic cells contained cathepsin D-related enzyme forms that are
      electrophoretically distinct from normal leukocyte cathepsin D. The present
      results are inconsistent with the view that cathepsin E may be involved as an
      essential factor in the biological functions of leukocytes or erythrocytes.

PMID- 1991131
TI  - Indomethacin attenuation of hepatic perfusion and plasma 6-ketoPGF1 alpha
      elevations following glutathione depletion in rabbits.
AB  - Glutathione (GSH) is important in detoxification and regulating cyclooxygenase
      activity. Since the liver has high levels of GSH, xenobiotic-induced changes in
      hepatic GSH could affect hepatic tissue blood perfusion (HP) via alterations in
      prostaglandin synthesis. In anesthetized male New Zealand rabbits, elevating GSH
      with GSH monoethyl ester had no affect on HP. Treatment of rabbits with diethyl
      maleate to deplete GSH also had no affect on HP in animals previously given GSH
      monoethyl ester. However, HP increased within 20 min in rabbits treated with
      diethyl maleate prior to GSH monoethyl ester. In another experiment, a similar
      rise in HP following GSH depletion was accompanied by arterial plasma 6-ketoPGF1
      alpha (the stable metabolite of prostacyclin) levels that were 4-times higher
      than in the controls. Plasma TxB2 (the stable metabolite of thromboxane) also
      increased following diethyl maleate, but only to levels that were 25-times lower
      than for 6-ketoPGF1 alpha. Since indomethacin blocked the rise in HP, as well as
      the increases in 6-ketoPGF1 alpha and TxB2, these results indicate changes in HP
      may occur following GSH depletion as a result of increased synthesis of one or
      more arachidonic acid metabolites and implicate prostacyclin as a possible
      mediator of this phenomenon.

PMID- 1991133
TI  - Characterization of the general anion-binding site in glutamate dehydrogenase
      NADPH complex.
AB  - The reductive amination of alpha-ketoglutarate, catalyzed by bovine liver
      glutamate dehydrogenase, is inhibited by various anions. Formate and acetate ions
      are competitive with alpha-ketoglutarate. The pH dependence of the pKi profiles
      for these anions reveals that they bind to the enzyme-NADPH complex only when an
      enzymatic residue of pK 8.0 +/- 0.1 in the binary complex is protonated. The
      ionization of this residue has a delta Hion of 15 +/- 4 kcal/mol. These pK and
      delta Hion values are not significantly different from those observed in the same
      complex for the enzyme group which binds the gamma-CO2- of alpha-ketoglutarate
      and oxalylglycine. It is concluded that formate and acetate also bind to the
      gamma-carboxylate site in enzyme-NADPH. The Ki values for formate and acetate in
      a buffer containing 0.1 M phosphate are 20 +/- 4 and 32 +/- 5 mM, respectively,
      when the pK 8.0 group is fully protonated. Phosphate and trifluoroacetate also
      show an inhibitory effect, while valerate and sulfate have little effect on the
      reductive amination rates. The results suggest that specific anions can bind to
      the gamma-carboxylate site by ionic interactions and alter the kinetic and
      thermodynamic parameters of the glutamate dehydrogenase-NADPH complex in
      significant ways.

PMID- 1991132
TI  - Microsomal chitinase activity from Candida albicans.
AB  - Chitinase (E.C. 3.2.1.14) was characterized in microsomal fractions from yeast
      cells of Candida albicans. Following six washes with buffer (50 mM Bis-Tris.Cl,
      pH 6.5), enzyme activity of microsomes fell markedly to 0.3% of total and 6% of
      the specific activity detected in the low-speed supernatant (9000 X g) of a cell
      lysate. An apparently zymogenic, microsomal chitinase activity became more
      readily detectable with washing and after six washes enzyme activity was
      activated 1.7-fold following pre-incubation with trypsin. The following
      properties of microsomal chitinase were closely comparable with those for
      cytosolic chitinase (indicated in parentheses): Km = 2.1 mg chitin per ml (2.9 mg
      chitin per ml); temperature optimum = 45 degrees C (45 degrees C); inhibition by
      allosamidin competitive, Ki = 0.29 microM (competitive, Ki = 0.23 microM). A
      range of detergents solubilized and activated microsomal chitinase in a highly
      specific manner. Following density gradient centrifugation of microsomes,
      chitinase was distributed approximately evenly throughout the gradient suggesting
      that microsomal chitinase is not associated exclusively with any one membrane
      component. The possible morphogenetic role of microsomal chitinase is discussed
      in relation to the potential of this enzyme as a target for highly specific
      antifungal agents.

PMID- 1991134
TI  - Two-hydronic-reactive states of acetylcholinesterase, mechanistically relevant
      acid-base catalyst of pKa 6.5 and a modulatory group of pKa 5.5.
AB  - Variation of experimentally observed pKa values in pH-dependent kinetic studies
      using acetylcholinesterase (AcChE) is rationalized by proposal of two-hydronic
      reactive states, EH and EH2, of the free AcChE molecule. Two kinetically
      influential ionizations with pKa 6.5 for the general acid-base catalyst, possibly
      the imidazole group of histidine, and a modulatory group with pKa 5.5 residing at
      the juxtaposal modulatory site, provided fundamental bases for the observed
      variation in pK(app) values. Appropriate equations applicable to the proposed
      kinetic model in conjunction with pKa values (pKI 5.5, pKII 6.5) and relative
      varied values of the pH-independent rate constants, k'cat/K'm and kcat/Km, of the
      reactive states were used to generate computer simulation error-free pH-rate
      profiles. A series of theoretical apparently simple sigmoidal pH-rate profiles
      with characterizing parameters pK(app) varying between 5.5-6.5 were obtained.
      Ionization of a modulatory group with pKa 5.5 alone modifies the reaction
      mechanism of AcChE, and binding of substrates and inhibitors at this site
      provides modulation of catalysis/binding at the active center. Analysis of the
      relative magnitudes of pH-independent rate constants for the two reactive states
      revealed that in terms of the overall catalysis, the EH state shows favorable
      reactivity towards the cationic reagents with reactivity 1.0, as compared to the
      EH2 state with reactivities 0.25-0.55. Neutral reagents, in general, make use of
      the EH2 state more than cationic reagents, with reactivities 1.0 for the EH state
      and 0.3-1.0 for the EH2 state. Further analysis showed that this discrimination
      between the two reactive states, by both types of reagents, occurs predominantly
      through the difference in binding constants K'm and Km. Relative binding of a
      given cationic reagent to the respective reactive states ranges from K'm = 1.8 X
      Km to 4.0 X Km, and from K'm = 1.0 X Km to 2.0 X Km for the neutral reagents.

PMID- 1991135
TI  - Interaction of nitrofurans with glutathione reductase.
AB  - Nitrofurans inhibit the oxidation of NADPH by glutathione, catalyzed by yeast
      glutathione reductase (EC 1.6.4.2). acting as uncompetitive incomplete inhibitors
      for NADPH and glutathione. The quinoline-substituted nitrofurans were the most
      effective inhibitors. These compounds increased the turnover numbers of enzyme at
      fixed concentrations of reduced glutathione, in the reverse reaction of
      glutathione reductase, but in most cases diminished the affinity of the enzyme
      for NAD+. Nitrofurans are weak one-electron oxidants of glutathione reductase.
      Their reactivity is close to that of p-quinones possessing the analoguous one
      electron reduction potential (Cenas, N.K., Rakauskiene, G.A. and Kulys, J.J.
      (1989) Biochim. Biophys. Acta 973, 399-404), and reaction is stimulated by NADP+.
      It is assumed, that nitrofurans bind to the 'regulative' site of glutathione
      reductase (Karplus, P.A., Pai, E.F. and Schulz, G.E. (1989) Eur. J. Biochem. 178,
      693-703).

PMID- 1991136
TI  - Activation by spermine of citrate synthase from porcine heart.
AB  - Spermine activated citrate synthase from porcine heart by decreasing the Km value
      for the substrate oxaloacetate without affecting the maximal velocity. Spermine
      markedly increased the maximal velocity of the saturation function with respect
      to acetyl-CoA as the substrate under conditions of intracellular concentrations
      of oxaloacetate, but the enzyme was not activated by spermine under conditions of
      higher concentrations of oxaloacetate. The concentration of spermine required for
      50% activation of the enzyme was about 50 microM. Spermidine showed only a little
      activation, while putrescine caused no activation. Spermine, which contributes to
      an activation of Ca2(+)-sensitive dehydrogenases of the citric acid cycle by
      enhancing Ca2+ uptake into mitochondria, can activate citrate synthase directly,
      and is responsible for the stimulation of oxidative metabolism in mitochondria.

PMID- 1991138
TI  - Azido derivative of tricarboxylic acid for photoaffinity labeling.
AB  - A new photoaffinity probe, 5-(1-hydroxy-4-azidophenylazo)-1,2,3
      benzenetricarboxylic acid, was synthesized and characterized. This reagent can be
      potentially used in photoaffinity labeling of the mitochondrial tricarboxylate
      carrier, as well as of enzymes interacting with tricarboxylic acids. Inhibition
      and labeling of the mitochondrial tricarboxylate carrier is presented.

PMID- 1991137
TI  - D-aspartate oxidase, a peroxisomal enzyme in liver of rat and man.
AB  - By means of subcellular fractionation D-aspartate oxidase was shown to be
      localized in peroxisomes in rat and human liver. The oxidase from both sources
      was most active on D-aspartate and N-methyl-D-aspartate. In different rat
      tissues, the highest enzyme activity was found in kidney, followed by liver and
      brain. In these tissues, oxidase activities became detectable 1-4 days after
      birth, reaching adult values after 4 weeks. Analysis of liver samples from
      patients with Zellweger syndrome, a generalized peroxisomal dysfunction,
      demonstrated no significant deficiency of this particular oxidase.

PMID- 1991139
TI  - New substrates of the multispecific bile acid transporter in liver cells:
      interference of some linear renin inhibiting peptides with transport protein(s)
      for bile acids.
AB  - Interactions between some stable linear peptides with renin inhibitory activity
      and a multispecific transport system in the basolateral plasma membrane of liver
      cells was studied on cell suspensions. The peptides used in our experiments were
      taken up by liver cells and subsequently eliminated without any biotransformation
      (e.g., proteolysis). No degradation products could be detected in the
      extracellular medium by thin-layer chromatography. All peptides tested inhibited
      the uptake of physiological and of some foreign substrates of the multispecific
      bile acid transporter (MT). The phalloidin response of liver cells was also
      inhibited to a similar degree in a concentration-dependent manner. The potency of
      inhibition did not correlate with the lipophilic properties of the peptides. On
      the other hand a tight correlation could be documented between the inhibition of
      cholate transport and that of the phalloidin response. Transport inhibition of
      typical substrates of the MT by the above renin inhibitors was competitive. In
      contrast, the transport of a typical substrate of the bilirubin carrier
      (rifampicin), of amino acids (alpha-aminoisobutyric acid), long chain fatty acids
      (oleic acid) and cationic compounds (thiamin hydrochloride) was not inhibited by
      the same renin inhibitors. These results indicate that linear renin inhibiting
      peptides are taken up into liver cells by carrier proteins related to the MT.

PMID- 1991140
TI  - Induction of heme oxygenase mRNA by cobalt protoporphyrin in rat liver.
AB  - The effect of cobaltic(III)-protoporphyrin on heme oxygenase activity and mRNA
      content was examined in vivo in the adult male rat liver. The activity of heme
      oxygenase, the rate-limiting enzyme in the degradation of heme, was enhanced, as
      expected, by cobalt protoporphyrin (25 mumol/kg body weight) in a time-dependent
      manner. Levels of enzyme activity were increased 2-fold by 8-16 h following
      treatment and were 6-fold higher than baseline values by 48 h. Administration of
      cobalt protoporphyrin resulted in a marked increase in heme oxygenase mRNA in the
      liver. Within 2 h of treatment, mRNA levels had increased 7.9-fold. The induction
      of heme oxygenase mRNA was maximal at 8 h when the levels were 58.5-fold above
      baseline. At every time point tested, the increase in heme oxygenase mRNA was
      several fold greater than that of enzyme activity.

PMID- 1991141
TI  - Structural determination of three neutral oligosaccharides in bovine (Holstein
      Friesian) colostrum, including the novel trisaccharide; GalNAc alpha 1-3Gal beta
      1-4Glc.
AB  - Two trisaccharides, and a pentasaccharide were obtained from bovine colostrum.
      Their chemical structures were determined by using methylation and 13C-NMR
      analyses as follows: GalNac alpha 1-3Gal beta 1-4Glc, Gal alpha-1-3Gal beta 1
      4Glc, GaL beta 1-3[Gal beta 1-4GlcNAc beta 1-6]Gal beta 1-4Glc. GalNAc alpha 1
      3Gal beta 1-4Glc, which was identified in this study, is a novel oligosaccharide
      from natural sources. Gal alpha 1-3Gal beta 1-4Glc and Gal beta 1-3[Gal beta 1
      4GlcNAc beta 1-6]Gal beta 1-4Glc (lacto-N-novopentaose) have been already found
      in ovine colostrum, and in horse colostrum and marsupial milk, respectively.

PMID- 1991142
TI  - Purification of histone H10 and its subfractions under non-denaturing conditions.
AB  - A quick and convenient method for a non-denaturing purification of histone H10
      and its subfractions from different mammalian sources is presented. It is based
      on cation-exchange chromatography on a CM-Sephadex C-25 column developed by a
      linear gradient of NaCl. The procedure allows a satisfactory fractionation of H10
      subfractions in a form suitable for further studies in assays requiring the
      native state of the protein.

PMID- 1991143
TI  - Carboxyl group orientation in K-palmitate/water using 13C double resonance
      spectroscopy.
AB  - 13C-NMR is used to probe the motion and orientation of the carboxyl group in a
      70% potassium palmitate/30% water mixture. An increase in delta sigma with
      increasing temperature corresponds to a change of orientation of the carboxyl
      group. Comparison with 2H-NMR and lineshape simulations show that near 57 degrees
      C the molecules exchange between two orientations at a rate between 10-500 Hz.

PMID- 1991144
TI  - Reversible binding of peptide aldehydes to papain. Structure-activity
      relationships.
AB  - The hydration of eleven peptide and hipuryl aldehydes has been measured as a
      function of temperature by means of NMR spectroscopy. In all cases the aldehydes
      were strongly hydrated (i.e., 90-95%) in aqueous solution. Dehydration of the
      hydrates was strongly endothermic, but this was partly offset by a positive
      entropy for dehydration. The binding of the aldehydes to papain was measured by
      fluorescence titration, and from these data dissociation constants for the
      hemithioacetal enzyme adducts were derived. Binding of N-Ac-L-PheNHCH2CHO (1) was
      particularly tight (Kd,corr = 0.00043 micro M) whereas that of its D-enantiomer
      (2) was 300-fold weaker (Kd,corr = 0.129 microM). The binding constants of the
      eleven aldehydes correlated with those for the reversible covalent binding of the
      analogous nitriles according to the equation log Kd(CHO) = -2.687 +/- 1.016 log K
      d(CN) (r = 0.99), lending support to previous suggestions that both peptide
      aldehydes and peptide nitriles behave as transition-state- or reactive
      intermediate analogs for papain. This finding is particularly striking in view of
      the obvious differences in hybridization (sp2 vs. sp3) and geometry (trigonal vs.
      tetrahedral) at the reactive P1 carbon center in their covalent adduct forms
      (thioimidate ester vs. hemithioacetal, respectively). A model for the binding of
      substrates, their transition states and analogs thereof is proposed. A key
      feature of the model is an obligatory covalent (or developing covalent)
      interaction between Cys-25-SH and the carbonyl or equivalent carbon of P1,
      augmented by intermolecular P1NH--OC(Asp-158), P2CO--HN(Gly-66) and P2NH--OC(Gly
      66) hydrogen bonds and a hydrophobic P2-S2 interaction. The latter three
      interactions are optimum or nearly optimum when P2 is a hydrophobic L-amino acid
      with an N-acyl substituent. Data presented suggest that hippuryl derivatives are
      relatively non-specific substrates or inhibitors for papain and, consequently,
      are of diminished value as probes for binding and catalytic studies.

PMID- 1991145
TI  - Purification and characterization of two endopolygalacturonases from Sclerotinia
      sclerotiorum.
AB  - The endopolygalacturonase (EC 3.2.1.15) enzyme produced in vitro by Sclerotinia
      sclerotiorum were found to consist of numerous isoforms covering a broad pI
      range. Two of the isoforms, labelled PG2 and PG3, were purified using gel
      filtration chromatography, isoelectric focusing and anion-exchange
      chromatography. The pIs of PG2 and PG3 were, respectively, 4.8 and 4.9. Their
      molecular weights were similar. Both enzymes hydrolysed 0.9% of the bonds in
      reaching a 50% reduction in viscosity. However, their enzymic parameters were
      different. Their amino acid compositions differed only in the aspartic acid
      asparagine content. The N-terminal sequences differed at the fourth amino acid
      only. PG2 and PG3 exhibited a high level of glycosylation compared to a similar
      enzyme isolated from Aspergillus niger. Antibody raised against PG3 was shown to
      crossreact with PG2, but not with the enzyme purified from Aspergillus niger.

PMID- 1991146
TI  - Purification and characterization of two endo-beta-1,4-D-glucanases from
      Sclerotinia sclerotiorum.
AB  - The endo-beta-1,4-D-glucanase (EC 3.2.1.4) enzymes produced in vitro by
      Sclerotinia sclerotiorum consisted of numerous isoforms with pI ranging from 3.5
      to 6.2. The two dominant isoforms, labelled EG1 and EG2, were purified. The pI of
      EG1 and EG2 were 6.2 and 3.7, respectively. Their molecular weights were,
      respectively, 48,000 and 34,000. EG1 and EG2 were both active towards
      carboxymethyl cellulose. However, EG1 was also active towards 4
      methylumbelliferyl cellobioside. The amino acid compositions of EG1 and EG2 were
      different. The N-terminal amino acid sequences of the two enzymes showed little
      homology. However, the N-terminal sequence of EG1 showed considerable homology to
      the published N-terminal sequence of an endoglucanase (EG1) from Schizohyllum
      commune.

PMID- 1991147
TI  - Isolation and characterization of cell adhesion molecules from the marine sponge,
      Ophlitaspongia tenuis.
AB  - Previous studies suggested that cell adhesion in the marine sponge,
      Ophlitaspongia tenuis, is mediated by a 35 kDa cell surface protein which
      interacts with an extracellular sulfated polysaccharide. This paper describes a
      simple and efficient procedure for isolating both putative cell adhesion
      molecules from detergent lysates of O. tenuis cells, the procedure being based on
      the fortuitous affinity of the sponge polysaccharide for heparin. The purified
      polysaccharide inhibits O. tenuis sponge cell aggregation, is highly sulfated and
      represents a glycosaminoglycan containing glucuronic acid. N-sulfated glucosamine
      and, possibly, glucose. The purified 35 kDa protein has a high affinity for the
      sponge polysaccharide and also, selectively interacts with dextran sulfate, a
      polysaccharide that has been shown previously to both bind to the sponge cell
      surface and inhibit aggregation of O. tenuis cells. Collectively, the data
      supports the hypothesis that the 35 kDa molecule is the major cell adhesion
      protein in O. tenuis. Preliminary data also suggests that the sponge contains an
      endogenous glycan hydrolase which can cleave the sponge polysaccharide.

PMID- 1991149
TI  - Purification and characterization of coenzyme F420-dependent 5,10
      methylenetetrahydromethanopterin dehydrogenase from Methanobacterium
      thermoautotrophicum strain delta H.
AB  - 5,10-Methylenetetrahydromethanopterin dehydrogenase from Methanobacterium
      thermoautotrophicum strain delta H was purified to homogeneity with nearly
      complete recovery. The aerobically stable monofunctional enzyme catalyzed the
      reversible oxidation of 5,10-methylene-5,6,7,8-tetrahydromethanopterin to its
      5,10-methenyl derivative. For the reaction a midpoint potential E'0 = - 362 mV
      was calculated at 60 degrees C. The methanogenic electron carrier coenzyme F420
      was strictly required as the co-substrate. The dehydrogenase (Mr 216,000) was
      purified as an apparent hexamer of six identical 36 kDa subunits. Oxidation of
      5,10-methylenetetrahydromethanopterin coupled to coenzyme F420 reduction
      catalyzed by the dehydrogenase with a turnover number of 2400 S-1 proceeded via a
      ternary complex mechanism. High concentrations of monovalent cations markedly
      stimulated the reaction.

PMID- 1991148
TI  - Effect of salt acclimation on digitalis-like compounds in the toad.
AB  - Digitalis-like compounds (DLC) were shown to be a normal constituent of the skin
      and plasma of toads. In order to assess the possible physiological role of these
      compounds in the toad, their levels were determined in the brain, plasma and skin
      following acclimation in different NaCl solutions. We demonstrate that an
      increase in salt concentrations in the animal medium from 0 to 1.2% decreased the
      levels of DLC in the brain by 50% without altering significantly its levels in
      the plasma and skin. An increase in medium salt concentration to 1.5% resulted in
      a 50% increase of DLC levels in the skin without changing its levels in the
      plasma or brain. These results suggest that skin and brain DLC may participate in
      the long-term salt and water homeostasis in the toad, while the plasma compound
      either participates in the short-term regulations of salt and water homeostasis
      or have some other, unknown, function.

PMID- 1991151
TI  - Structural and functional features of different types of cytoplasmic fatty acid
      binding proteins.

PMID- 1991150
TI  - Extraction of proteins from material rich in anionic mucilages: partition and
      fractionation of vanadate-dependent bromoperoxidases from the brown algae
      Laminaria digitata and L. saccharina in aqueous polymer two-phase systems.
AB  - For various reasons extraction of proteins from plant material is difficult. In
      particular phenolic compounds and polyanionic cell-wall mucilages render
      conventional procedures of extraction and purification much more difficult. In
      this respect, aqueous polymer two-phase systems are presented as a powerful
      technique in extraction of vanadate-dependent bromoperoxidases from the brown
      macroalga Laminaria digitata, a seaweed extremely rich in mucilages. Little
      bromoperoxidase activity was obtained when fresh thallus material was extracted
      in Tris buffer. Extraction from freeze-dried and powdered material was more
      efficient but only satisfactory when partitioning in an aqueous polymer two-phase
      system was employed. Among several two-phase systems tested, one composed of
      poly(ethylene glycol) (PEG 1550) and potassium carbonate proved most successful
      (phase system-1). A rapid and efficient extraction procedure was developed with
      special regard for suitability in large scale processes. Staining for catalytic
      activity after PAGE revealed a pattern of several bromoperoxidase isoforms.
      Bromoperoxidases extracted in phase system-1 were fractionated into two groups of
      isoforms by partitioning in a second system (phase system-2) indicating that
      isoforms from both groups differ significantly in surface properties.
      Subsequently, one purification step by hydrophobic interaction chromatography was
      sufficient to remove residual non-peroxidase proteins as well as remaining
      polysaccharides from bromoperoxidases of both groups. Thus, consideration of
      aqueous two-phase systems as a technique for extraction and purification of plant
      proteins can be recommended, whenever inconveniant amounts of phenolic compounds,
      mucilages or pigments are present.

PMID- 1991152
TI  - Cerebral low-density lipoprotein (LDL) uptake is stimulated by acute bile
      drainage.
AB  - Although the cholesterol pool in the central nervous system is considered to be
      relatively stable, few studies have tested this assumption. The aim of the study
      was to gain further information on the communication between the extracerebral
      organs and the brain as far as cholesterol and lipoprotein transport are
      concerned. Receptor-dependent as well as receptor-independent LDL uptake in the
      brain were measured, by established methods, after constant 1-h intravenous
      infusions of [14C]sucrose-labelled hamster LDL and methylated human LDL, both in
      hamsters with an acute bile fistula and in control animals with an intact
      enterohepatic circulation. The receptor-dependent LDL uptake in the brain
      promptly showed a significant increase after the construction of the bile
      fistula. However, there was no difference in the receptor-independent LDL uptake
      between the bile fistula and control animals. The studies indicate the presence
      of close communications between extracerebral and brain cholesterol. Changes in
      the extracerebral compartments of cholesterol are, apparently, readily sensed by
      the LDL receptor in the brain and promptly evoke appropriate modifications in its
      activity.

PMID- 1991153
TI  - Eicosapentaenoic acid ethyl ester as an antithrombotic agent: comparison to an
      extract of fish oil.
AB  - Evidence suggesting that dietary omega-3 polyunsaturated fatty acids decrease the
      risk of thrombosis comes mainly from studies involving supplementation with large
      amounts (15-20 g/day) of fish oil extract. We investigated the inhibition of
      platelet function by a moderate amount (4 g/d) of ethyl eicosapentaenoate (E-EPA)
      compared to a concentrated fish oil extract (6 g/d) when given as a supplement to
      an ordinary diet. We also determined the effects of these supplements on platelet
      EPA incorporation, thromboxane synthesis, calcium mobilization and fibrinogen
      binding. After 4 weeks, both omega-3 supplements increased the amount of EPA in
      platelet phospholipids. The fish oil extract, which contained docosahexaenoic
      acid (DHA), had increased the amount of DHA also. The total increase in omega-3
      fatty acids was similar for both supplements. E-EPA decreased serum cholesterol
      by 13% and triacylglycerols, 35%; increased the bleeding time by 57% and the
      threshold dose of collagen needed to induce platelet aggregation by 46%.
      Thromboxane synthesis in response to collagen was decreased 65% by E-EPA. Thus,
      the dietary supplement of pure E-EPA was more effective in limiting platelet
      reactivity than a concentrated fish oil extract providing an equivalent amount of
      omega-3 fatty acids. As an antithrombotic agent, E-EPA should allow for
      reasonable daily doses in long-term treatment of cardiovascular disease.

PMID- 1991154
TI  - Cholestasis induced by lithocholate and its glucuronide: their biliary excretion
      and metabolism.
AB  - We studied the effects of the infusion of lithocholate and lithocholate-3-sulfate
      and 3-glucuronide in rats (0.29 mumol/min per 100 g body weight for 40 min) on
      bile flow, together with their biliary excretion and metabolism. Lithocholate
      glucuronide had a higher cholestatic effect than lithocholate, whereas
      lithocholate-sulfate had almost no effect on bile flow. Lithocholate was mainly
      converted to taurine or glucuronide conjugates in the bile, serum and liver and
      hydroxylation of the tauro-conjugate proceeded. Lithocholate-sulfate was almost
      completely excreted in the bile, mainly as tauro-conjugate. Lithocholate
      glucuronide was excreted in bile almost without conjugation, while some taurine
      conjugation occurred in the serum and liver. These results suggest that the poor
      biotransformation of lithocholate-glucuronide is related to its higher
      cholestatic potency than lithocholate.

PMID- 1991155
TI  - Surface properties and sensitivity to protein-inhibition of a recombinant
      apoprotein C-based phospholipid mixture in vitro--comparison to natural
      surfactant.
AB  - Surfactant alterations due to protein leakage are implicated in the pathogenesis
      of the adult respiratory distress syndrome. In the present study, surface
      properties of a palmitic acid containing phospholipid mixture (DPPC: PG:
      PA/68.5:22.5:9) supplemented with 2% recombinant human surfactant apoprotein C
      (PLM-Crec) were compared to those of the lipids alone (PLM) and to those of calf
      lung surfactant extract (CLSE). Experiments were performed in a Wilhelmy balance
      and in a pulsating bubble surfactometer. Adsorption facilities and dynamic
      surface tension-lowering properties of the surfactants alone, their sensitivity
      to the inhibitory effect of fibrinogen (fbg), and their capacity to restore
      surface properties of fbg-inhibited CLSE were investigated. PLM revealed limited
      surface activity, was very sensitive to inhibition by fbg and had moderate effect
      on the surface properties of fbg-inhibited CLSE. In contrast, PLM-Crec and CLSE
      revealed similar excellent adsorption kinetics and dynamic surface tension
      lowering properties. Higher percentage of SP-C within the synthetic mixture (up
      to 10%) or additional admixture of human purified or recombinant SP-A (up to 10%)
      did not further improve these surface properties. However, PLM-Crec was markedly
      more sensitive to inactivation by fbg than CLSE. The surface activity of fbg
      inhibited CLSE was fully restored by additional admixture of CLSE or PLM-Crec in
      both the Wilhelmy and the bubble system, with slight superiority of the natural
      surfactant extract. We conclude that the surface properties of PLM-Crec are
      clearly superior to those of the apoprotein-free lipid mixture and are similar to
      those of the natural surfactant extract CLSE. PLM-Crec is markedly more sensitive
      to inhibition by fibrinogen than CLSE, but possesses nearly equivalent efficacy
      in restoring the surface properties of fbg-inhibited CLSE as compared to the
      natural material.

PMID- 1991156
TI  - Appearance of surfactant proteins, SP-A and SP-B, in developing rat lung and the
      effects of in vivo dexamethasone treatment.
AB  - Hydrophobic pulmonary surfactant proteins (SP-B and SP-C) promote the adsorption
      of phospholipids at the air/liquid interface and the addition of surfactant
      protein A (SP-A) enhances this function. The developmental profiles of
      phospholipids and SP-A in the lung have been reported, but that of SP-B and SP-C
      remain unknown. We recently developed an enzyme-linked immunosorbent assay
      (ELISA) that measures SP-B in the rat. Using ELISA for SP-A and SP-B, we measured
      the contents of SP-A and SP-B in lung homogenates. The developmental profiles of
      SP-A and SP-B during the late gestational and postnatal periods were found to be
      distinctly different from each other. SP-A increased during late gestation and
      reached its maximum on day 1 after birth. This developmental profile of SP-A in
      the lungs was very similar to that of disaturated phosphatidylcholine (DSPC). In
      contrast, the SP-B contents in fetal lungs were low and increased after birth,
      reaching its maximum on day 4 after birth. In vivo dexamethasone treatment
      resulted in significant increases of SP-A content in rat lung homogenate on day
      19 and day 21 of gestation, and day 5 after birth, whereas SP-B content increased
      significantly only on day 19 of gestation by dexamethasone administration. SP-A
      synthesis may be enhanced both pre- and postnatally, but SP-B synthesis may be
      stimulated only during the late gestational period by in vivo dexamethasone
      treatment. The difference in developmental profiles and the different responses
      to dexamethasone treatment between SP-A and SP-B indicate that the expression of
      SP-A and SP-B may be regulated independently at least in developing rat lungs.

PMID- 1991157
TI  - Fatty acid composition of the rat pineal gland. Dietary modifications.
AB  - When compared to brain, the fatty acid composition of the rat pineal gland
      revealed that the total proportion of n-6 polyunsaturated fatty acids (PUFA) was
      2.3-fold higher, whereas the proportion of n-3 fatty acids was similar.
      Specifically, 20:4(n-6) and 18:2(n-6) were respectively 1.56- and 11.80-fold
      higher in the pineal than in the brain, while the proportions of 22:6(n-3) were
      similar in both tissues. In addition, 18:1(n-9) was found 2.15-fold lower in the
      pineal. Feeding adult rats with fish oil concentrates induced a significant
      alteration of the polyunsaturated fatty acid composition of the pineal. There was
      a reciprocal replacement of the n-6 by the n-3 fatty acids. Conversely, in rats
      fed a n-3 fatty acid-deficient diet (sunflower oil or coconut oil diet), the
      pineal gland contained reduced proportions of n-3 fatty acids. We conclude that
      the pineal gland (i) differs from the brain in containing much higher proportions
      of 18:2(n-6) and from the other tissues for its high proportions of 22:6(n-3) and
      (ii) is highly sensitive to the n-3 fatty acid diet in contrast to what is known
      for the brain. These findings are discussed in the context of melatonin
      biosynthesis, the major hormone of the pineal gland.

PMID- 1991158
TI  - Eicosanoid-dependent and -independent formation of individual [14C]stearoyl
      labelled lysophospholipids in collagen-stimulated human platelets.
AB  - Low level collagen activation of platelets is mediated via the release of
      arachidonic acid (AA) from membrane phospholipids and the formation of
      thromboxane A2 (TxA2). To assess the specific phospholipids undergoing
      deacylation via phospholipase A2 thereby providing source(s) of releasable AA, we
      have measured the individual lysophospholipid formations in platelets prelabelled
      with [14C]stearic acid and incubated with a low level (2 micrograms/ml) or a high
      level (10 micrograms/ml) of collagen in the absence or presence of BW755C, a dual
      inhibitor of cyclooxygenase and lipoxygenase activities. Collagen activation
      resulted in the generation of [14C]stearoyl-labelled lysophosphatidylinositol
      (lysoPI), lysophosphatidylcholine (lysoPC), lysophosphatidylethanolamine (lysoPE)
      and lysophosphatidylserine. BW755C significantly inhibited these collagen-induced
      changes, suggesting that much of the lysophospholipid, and therefore AA release,
      was eicosanoid-mediated. At the lower level of collagen, considerable generation
      of [14C]lysoPE was maintained even in the presence of BW755C, suggesting an
      eicosanoid-independent degradation of phosphatidyl-ethanolamine. The TxA2
      dependent release of AA was also investigated in U-46619-stimulated platelets.
      This TxA2 mimetic induced considerable formation of the 14C-labelled
      lysophospholipids, including lysoPI and lysoPC, but not lysoPE. These results
      suggest that an eicosanoid-independent degradation of phosphatidylethanolamine
      via phospholipase A2 at lower collagen levels may provide a source of the initial
      AA for conversion to TxA2 and the subsequent deacylation of phosphatidylinositol,
      phosphatidylcholine, and also phosphatidylserine.

PMID- 1991159
TI  - Erythropoietin.

PMID- 1991160
TI  - Translocation (9;22) is associated with extremely poor prognosis in intensively
      treated children with acute lymphoblastic leukemia.
AB  - The prognostic implications of t(9;22)(q34;q11) were assessed at a median follow
      up of 3.5 years in 434 children receiving intensive treatment for acute
      lymphoblastic leukemia (ALL). Four-year event-free and overall survivals were 81%
      and 88%, respectively, in 419 children lacking t(9;22), but were 0% and 20%,
      respectively, in 15 children with t(9;22) (P less than .001). Poor outcome for
      children with t(9;22)-positive ALL was particularly notable because we have
      reported improved survival in other historically poor prognosis ALL cytogenetic
      categories when treated with similarly intensive therapy. We recommend that very
      intensive treatment approaches, including bone marrow transplantation in first
      remission, be considered for all children with t(9;22)-positive ALL.

PMID- 1991161
TI  - Clinical characteristics and treatment outcome of childhood acute lymphoblastic
      leukemia with the t(4;11)(q21;q23): a collaborative study of 40 cases.
AB  - The t(4;11)(q21;q23) chromosomal abnormality was identified in 40 (2%) of 1,986
      children with newly diagnosed acute lymphoblastic leukemia (ALL). This
      translocation was associated with female sex (63%), age less than 1 year (60%),
      hyperleukocytosis (median leukocyte count, 156.5 x 10(9)/L), CD10-/CD19+ B
      precursor cell immunophenotype, and myeloid-associated antigen (CD15) expression
      (63%). Nearly all cases had at least some CD24- blast cells. The CD10
      /CD15%/CD19+/CD24/+ phenotype was found in 20 of the 32 t(4;11) cases tested.
      None of the 40 cases had the cytogenetic finding of hyperdiploidy greater than
      50, which is a favorable prognostic feature. For clinical comparison, the t(4;11)
      cases were divided into three groups according to age at diagnosis: less than 1
      year (n = 24), 1 to 9 years (n = 8), and greater than or equal to 10 years (n =
      8). Compared with older patients, infants were more likely to have initial
      central nervous system leukemia (P = .05) and less likely to have pre-B-cell ALL
      (P = .05). Complete continuous remission has been maintained in only 7 of 24
      infants and 2 of 8 patients aged greater than or equal to 10 years, in contrast
      to 7 of 8 children in the intermediate age group (P = .048). These findings
      suggest that the t(4;11) is an adverse prognostic feature in these two age
      groups.

PMID- 1991162
TI  - Abnormal megakaryocytopoiesis in the Belgrade laboratory rat.
AB  - The Belgrade laboratory (b/b) rat has a hereditary hypochromic microcytic anemia
      because of defective transmembrane iron transport into erythroblasts. The present
      study was prompted by our previous work in which we showed that the b/b rat has
      hypomegakaryocytic thrombocytopenia associated with increased megakaryocyte size.
      To define the basic mechanism underlying this abnormality in the b/b rat we have
      studied both megakaryocytopoiesis and granulopoiesis in anemic b/b rats,
      chronically transfused b/b rats, iron-treated b/b rats, and controls. We have
      found decreased concentrations of megakaryocyte and granulocyte progenitors in
      the marrow of b/b rats. Full correction of the severe anemia by chronic
      transfusion resulted in normalization of megakaryocyte progenitors, small
      acetylcholinesterase positive cells, megakaryocyte size, and platelet counts,
      along with granulocyte progenitors. In contrast, the partial correction of anemia
      obtained by iron treatment resulted in improvement, but not normalization, of
      these parameters. These findings indicate that abnormal megakaryocytopoiesis in
      the b/b rat can be best interpreted as a consequence of hypoxia because of the
      severe anemia. Because we have recently shown that the number of erythroid
      progenitors in b/b rats is also low, we propose that abnormal
      megakaryocytopoiesis in this animal is a reflection of an acquired stem cell
      disorder induced by the prolonged hypoxia resulting from the severe anemia.

PMID- 1991163
TI  - Interleukin-6 and its receptor are expressed by human megakaryocytes: in vitro
      effects on proliferation and endoreplication.
AB  - Interleukin-6 (IL-6) is a pleiotropic cytokine that plays an important role in
      the megakaryocytic differentiation. Recently, we have observed that IL-6 is
      synthesized by several human cell lines with megakaryocytic features. In this
      study, we have investigated whether a similar phenomenon occurs during normal
      megakaryocytic differentiation. Human megakaryocytes (MK) were obtained by
      culturing normal marrow in liquid culture with aplastic plasma (AP). First, an IL
      6 secretion in bone marrow culture enriched in MK as well as in purified MK
      populations was demonstrated by a biologic assay. Second, IL-6 mRNA was detected
      in a purified population of MK by the polymerase chain reaction and dot blot
      analysis. IL-6 mRNA and protein were undetectable in platelets. Third, in situ
      hybridization procedure demonstrated the presence of IL-6 mRNA in individual
      immature MK. Fourth, IL-6 protein was detected in MK at the unicellular level by
      an immunoalkaline phosphatase technique using a monoclonal antibody against IL-6.
      Furthermore, the presence of IL-6 receptor (IL-6-R) on MK was demonstrated by in
      situ hybridization using an IL-6-R probe and in situ autoradiography after
      binding with [125I]-labeled recombinant IL-6. The IL-6 endogenously produced in
      liquid cultures containing normal human plasma or AP was subsequently
      neutralized. This resulted in a 50% decrease of the MK growth with a minor shift
      in the ploidy distribution toward lower values. In semisolid cultures the
      addition of anti-IL-6 antibodies led to a 42% decrease in colony number in
      cultures stimulated by IL-3 but not in other conditions of culture. These results
      suggest that normal human megakaryocytopoiesis might be regulated in part by an
      IL-6 autocrine loop.

PMID- 1991164
TI  - Administration of interleukin-6 stimulates multilineage hematopoiesis and
      accelerates recovery from radiation-induced hematopoietic depression.
AB  - Hematopoietic depression and subsequent susceptibility to potentially lethal
      opportunistic infections are well-documented phenomena following radiotherapy.
      Methods to therapeutically mitigate radiation-induced myelosuppression could
      offer great clinical value. In vivo studies in our laboratory have demonstrated
      that interleukin-6 (IL-6) stimulates pluripotent hematopoietic stem cell (CFU-s),
      granulocyte-macrophage progenitor cell (GM-CFC), and erythroid progenitor cell
      (CFU-e) proliferation in normal mice. Based on these results, the ability of IL-6
      to stimulate hematopoietic regeneration following radiation-induced hematopoietic
      injury was also evaluated. C3H/HeN female mice were exposed to 6.5 Gy 60Co
      radiation and subcutaneously administered either saline or IL-6 (1,000
      micrograms/kg) on days 1 through 3 or 1 through 6 postexposure. On days 7, 10,
      14, 17, and 22, femoral and splenic CFU-s, GM-CFC, and CFU-e contents and
      peripheral blood white cell, red cell, and platelet counts were determined.
      Compared with saline treatment, both 3-day and 6-day IL-6 treatments accelerated
      hematopoietic recovery; 6-day treatment produced the greater effects. For
      example, compared with normal control values (N), femoral and splenic CFU-s
      numbers in IL-6-treated mice 17 days postirradiation were 27% N and 136% N versus
      2% N and 10% N in saline-treated mice. At the same time, bone marrow and splenic
      GM-CFC values were 58% N and 473% N versus 6% N and 196% N in saline-treated
      mice; bone marrow and splenic CFU-e numbers were 91% N and 250% N versus 31% N
      and 130% N in saline-treated mice; and peripheral blood white cell, red cell, and
      platelet values were 210% N, 60% N, and 24% N versus 18% N, 39% N, and 7% N in
      saline-treated mice. These studies demonstrate that therapeutically administered
      IL-6 can effectively accelerate multilineage hematopoietic recovery following
      radiation-induced hematopoietic injury.

PMID- 1991165
TI  - Human immunodeficiency virus infection of megakaryocytic cells.
AB  - The human immunodeficiency virus (HIV) is capable of infecting certain cells of
      hematopoietic lineage, particularly monocyte-macrophages and T lymphocytes.
      Recently, the possibility that cells of megakaryocytic lineage are susceptible to
      HIV infection has been raised. We have characterized infection of the permanent
      megakaryocytic cell line CMK by HIV in vitro. CMK cells were easily infected by
      HIV type 2 (HIV-2), producing significant amounts of virus in culture. Infection
      appeared to be mediated by the CD4 surface antigen on CMK cells. Three different
      strains of HIV-1 were able to minimally infect CMK cells, suggesting there may be
      isolates of HIV tropic for megakaryocytes. Infection of CMK cells led to
      downregulation of the CD4 surface antigen but no discernable change in expression
      of megakaryocyte-associated proteins glycoprotein Ib and glycoprotein IIb/IIIa.
      These observations support the likelihood that megakaryocytes are susceptible to
      HIV infection, and cell lines of megakaryocytic origin may provide a useful model
      to study effects of the retrovirus on megakaryocyte function.

PMID- 1991166
TI  - Role of von Willebrand factor associated to extracellular matrices in platelet
      adhesion.
AB  - The respective role of plasmatic and endothelial extracellular matrix (ECM)
      associated von Willebrand factor (vWF) in platelet adhesion was investigated at a
      high shear rate using a parallel-plate perfusion chamber. Incubation of the
      endothelial ECM with a monoclonal antibody (MoAb) to vWF, which specifically
      blocks vWF binding to platelet GP Ib (MoAb 322), inhibited 45% of platelet
      adhesion. Complete inhibition was achieved by incubating both plasma and
      endothelial ECM with MoAb 322 at concentrations that blocked only about 50% of
      adhesion when added separately. The effect of ECM-associated vWF was further
      demonstrated when a fibroblastic ECM, normally devoid of vWF, was coated with
      purified plasmatic vWF. Matrix associated-vWF was able to significantly enhance
      platelet adhesion in both the presence and the absence of plasmatic vWF. In
      contrast, this effect was not seen on endothelial ECM. Binding of exogenous vWF
      to the ECM was specific and dose dependent, reached the same value (500 ng/cm2)
      on both fibroblastic ECM and endothelial ECM, but exhibited a threefold-lower
      apparent dissociation constant (KD) on fibroblastic than on endothelial ECM. Our
      studies suggest that vWF deposited by endothelial cells in the ECM may be the
      most active form in platelet adhesion, whereas plasmatic vWF may only play a
      secondary role.

PMID- 1991167
TI  - Developmental expression of mRNAs encoding platelet proteins in rat
      megakaryocytes.
AB  - The committed bone marrow megakaryocyte (MK) progenitor undergoes a series of
      highly regulated stages of development resulting in a large multi-nucleated
      platelet-producing cell. We studied the developmental expression of the mRNA for
      two alpha granule proteins, fibronectin (FN) and fibrinogen gamma chain (gamma
      FIB), and a cytoskeletal protein, actin, in MKs from marrow of Sprague-Dawley
      rats. By the method of in situ RNA:RNA hybridization, we showed that mRNAs for
      the alpha granule proteins were expressed most abundantly in a population of 15
      microns diameter promegakaryocytes and in cells as small as 10 microns whose
      identity as immature MKs was inferred by positive staining for platelet- and MK
      specific markers. gamma-FIB and FN mRNAs were present in reduced abundance in a
      small proportion of intermediate MKs; however, little or no expression was seen
      in mature platelet-producing MKs. In contrast, high levels of actin mRNA were
      expressed predominantly in mature, multi-nucleated MKs, and less abundantly in
      the immature forms. These results suggest that FN and gamma-FIB are transcribed
      early in MK development to permit translation and packaging of the protein into
      alpha granules, after which transcription ceases. On the other hand,
      transcription of actin occurs continuously throughout development, with highest
      levels in mature platelet-producing MKs, in which actin is needed for shape
      changes and intracellular movement of organelles. Our data suggest that in situ
      RNA:RNA hybridization for platelet-specific markers will provide additional
      criteria by which to establish MK lineage in immature marrow progenitors.

PMID- 1991169
TI  - Characterization of an interleukin-6-mediated autocrine growth loop in the human
      multiple myeloma cell line, U266.
AB  - It has been reported recently that freshly isolated human myeloma cell cultures
      proliferate in response to added interleukin-6 (IL-6). Endogenous levels of IL-6
      found in the same cultures suggested that an autocrine growth loop may contribute
      to cell growth. However, the lack of homogenous cell populations in primary
      myeloma cultures has made it difficult to distinguish between paracrine and
      autocrine growth mechanisms. To precisely address the autocrine growth issue we
      have evaluated the growth of the human myeloma cell line, U266. We have found
      that a neutralizing anti-IL-6 monoclonal antibody can inhibit U266 proliferation.
      Furthermore, the addition of IL-6 antisense oligonucleotides also inhibits U266
      proliferation. These effects are reversed by adding IL-6, suggesting the presence
      of an autocrine loop. Using bioassays with two different IL-6-dependent cell
      lines, we were able to detect IL-6 in concentrated U266 supernatants. IL-6 mRNA
      was detected by polymerase chain reaction amplification of cDNA. Cell cycle
      parameter analysis shows that IL-6 acts to release a block in G1. Taken together
      these results present conclusive evidence for IL-6-mediated autocrine growth in
      the U266 human myeloma cell line.

PMID- 1991168
TI  - Expression of a heat-inducible gene of the HSP70 family in human myelomonocytic
      cells: regulation by bacterial products and cytokines.
AB  - In this study we have examined the expression of a heat-shock protein (HSP) 70
      gene in normal human peripheral blood leukocytes. Northern blot analysis showed
      that appreciable levels of hsp70 mRNA are present in monocytes and granulocytes,
      whereas transcript levels were barely detectable or absent in lymphocytes.
      Monocytes functionally activated by bacterial lipopolysaccharide (LPS) showed an
      early (15 minutes) increase of hsp70 transcripts that was shown, by actinomycin D
      blocking and nuclear run-off experiments, to be dependent on transcriptional
      activation of the gene. LPS did not appreciably affect the hsp70 mRNA half-life.
      Monocytes exposed to inactivated streptococci, phorbol-12-myristate-13-acetate,
      and tumor necrosis factor showed augmented levels of hsp70 transcripts, whereas
      interferon-gamma and monocyte, granulocyte, and granulocyte-monocyte colony
      stimulating factors had no effect. Adherence to plastic augmented hsp70
      expression in monocytes. S1 protection analysis indicated that the gene expressed
      in monocytes is indeed a heat-inducible member of the hsp70 gene family rather
      than a constitutively expressed heat-shock cognate gene. Western blot analysis
      showed that a heat-inducible HSP72 was present in monocytes and, at augmented
      levels, in LPS-treated monocytes. LPS-activated monocytes were more resistant to
      heat shock than unstimulated cells. These data indicate that a heat-inducible
      hsp70 gene can be efficiently expressed in myelomonocytic cells at physiologic
      temperatures. Expression of hsp70 genes in monocytes suggests a possible role of
      heat-inducible genes in the differentiation and/or functional activation of
      terminally differentiated nonproliferating elements of the myelomonocytic
      lineage.

PMID- 1991170
TI  - Mutations of the ras proto-oncogenes in childhood monosomy 7.
AB  - ras gene mutations are the most frequent molecular changes found in the
      preleukemic syndromes of adults and may play a role in initiating these diseases
      and in their progression to acute leukemia. However, little is known about the
      incidence or importance of these genetic mutations in childhood
      myeloproliferative states (MPS). The bone marrow (BM) monosomy 7 syndrome
      accounts for a large percentage of childhood MPS. Although the duration of the
      MPS is quite variable, children with monosomy 7 eventually develop acute myeloid
      leukemia (AML). We investigated 20 children (13 with MPS, 7 with AML) with BM
      monosomy 7 or 7q- for the presence of ras gene mutations using the polymerase
      chain reaction and hybridization with mutation-specific oligonucleotides.
      Mutations of N-ras and K-ras were detected in three children. Two patients
      carrying a ras mutation were in the myeloproliferative phase, and one had acute
      leukemia. All three patients with ras mutations either died of their disease or
      relapsed after BM transplantation as compared with 8 of 17 without ras mutations.
      However, this difference is not statistically significant (P = .14, not
      significant). We conclude that ras mutations are observed in childhood monosomy
      7, though less frequently than in adult MDS, and may play a limited role in the
      progression of this disease to acute leukemia. More patients are needed to
      address the prognostic role of ras mutations in this rare disease.

PMID- 1991171
TI  - Comparison of serum anti-band 3 and anti-Gal antibody binding to density
      separated human red blood cells.
AB  - This study examines the quantitative relationship between two natural serum
      antibodies, anti-band 3 and anti-alpha-galactosyl (anti-Gal), in their capacity
      to bind to human red blood cell (RBC) populations separated on density gradients.
      The question was approached in two ways. First, we determined the extent of
      rebinding of affinity-purified human serum antibodies to RBCs that had been
      stripped of in situ antibody. Second, we eluted the in situ bound antibody at low
      pH from density-separated RBCs and determined the proportion of total eluted
      antibody that bound specifically to erythrocyte band 3 or to a Gal-alpha-(1,3)
      Gal structure. Our results show that high-density human RBCs bind increased
      amounts of both antibodies. Anti-Gal rebinding was specific, because it was
      saturable and occurred in the presence of serum IgG depleted of anti-Gal. Binding
      assays using control natural autoantibodies directed against antigens not found
      on the RBC surface showed that high-density RBCs also bind increased amounts of
      these antibodies as compared with low-density RBCs. However, the extent of this
      binding is substantially lower than that of anti-band 3 and anti-Gal. Binding
      studies using the lectins Bandeiraea Simplicifolia (alpha-galactosyl specific)
      and Arachis Hypogaea (peanut agglutinin, beta-galactosyl specific) indicated that
      only the alpha-galactosyl sites are exposed on high density RBCs, and not the
      beta-galactosyl structure characteristic of T antigen. Antibody that is eluted at
      low pH from high density RBCs contains a 5.0% to 18.0% component that binds to
      band 3 protein, and a 9.1% to 39.0% component that recognizes the alpha
      galactosyl structure. Together, the two antibodies appear to constitute an
      average of 35% (range 17.2% to 57.4%) of the in situ bound antibody from high
      density human RBCs.

PMID- 1991172
TI  - The effect of N-alkyl modification on the antimalarial activity of 3
      hydroxypyridin-4-one oral iron chelators.
AB  - The antimalaria effect of iron chelators is attributed to their interaction with
      a labile iron pool within parasitised erythrocytes, and it was postulated that
      increased affinity to iron as well as increased lipophilicity may improve
      antimalarial activity. In the present study we have examined the antimalarial
      effect of 3-hydroxypyridin-4-ones, a family of bidentate orally effective iron
      chelators whose lipophilicity may be modified by altering the length of the R2
      substituent on the ring nitrogen. A significant dose-related suppression of
      Plasmodium falciparum cultures was observed with all drugs tested in vitro at
      concentrations of 5 mumol/L or higher. In contrast, there was a clear segregation
      of the in vivo effect on P berghei in rats (300 mg/kg/d subcutaneous) into two
      categories: compounds CP20, 38, and 40 failed to suppress malaria, whereas CP51,
      94, and 96 had a strong antimalarial effect, similar or better than deferoxamine.
      There was a close linear correlation between the suppression of peak parasite
      counts and the reduction in hepatic nonheme iron induced by the various drugs
      tested (r = .9837). The most lipophilic compounds were also the most effective in
      suppressing malaria and in depleting hepatic iron stores. These data indicate
      that 3-hydroxypyrydin-4-ones are able to suppress malaria in vivo and in vitro.
      Because lipid solubility is an important determinant of antimalarial action, our
      study provides useful information regarding the selection of orally effective
      iron-chelating compounds that may be suitable for clinical application as
      antimalarial agents.

PMID- 1991173
TI  - Molecular characterization of erythrocyte glycophorin C variants.
AB  - Human erythrocyte glycophorin C plays a functionally important role in
      maintaining erythrocyte shape and regulating membrane mechanical stability.
      Immunochemical and serologic studies have identified a number of glycophorin C
      variants that include the Yus, Gerbich, and Webb phenotypes. We report here the
      molecular characterization of these variants. Amplification of glycophorin C mRNA
      from the Yus phenotype, using two oligonucleotide primers that span the coding
      domain, generated a 338-bp fragment compared with a 395-bp fragment generated by
      amplification of normal glycophorin C mRNA. Sequencing of the mutant 338-bp
      fragment identified a 57-bp deletion that corresponds to exon 2 of the
      glycophorin C gene. Similar analysis showed deletion of 84-bp exon 3 in the
      Gerbich phenotype. In contrast to the generation of shorter than normal DNA
      fragments from mRNA amplification in the Yus and Gerbich phenotypes,
      amplification of mRNA from the Webb phenotype generated a normal-sized fragment.
      Sequencing of this DNA fragment showed an A----G substitution at nucleotide 23 of
      the coding sequence, resulting in the substitution of asparagine by serine. This
      modification accounts for the altered glycosylation of glycophorin C seen in this
      phenotype. These results have enabled us to characterize glycophorin C variants
      in three different phenotypes that involve deletions of exons 2 and 3 of the
      glycophorin C gene, as well as a point mutation in exon 1 that results in altered
      glycosylation of this protein.

PMID- 1991174
TI  - Evidence of a graft-versus-lymphoma effect associated with allogeneic bone marrow
      transplantation.
AB  - The existence of an immunologic antileukemia reaction associated with allogeneic
      bone marrow transplantation (BMT) is well established. However, a similar graft
      versus-tumor effect against lymphomas has not been demonstrated. We analyzed the
      results of BMT in 118 consecutive patients with relapsed Hodgkin's disease or
      aggressive non-Hodgkin's lymphoma. The 38 patients less than 50 years of age with
      HLA-matched donors had allogenic marrow transplants, and the other 80 patients
      received purged autologous grafts. The median age was 26 years in both the
      allogeneic and the autologous graft recipients. The patient's response to
      conventional salvage therapy before transplant was the only factor that
      influenced the event-free survival after BMT (P less than .001). Both the
      patient's response to salvage therapy before BMT (P less than .001) and the type
      of graft (P = .02) significantly influenced the probability of relapse after BMT.
      The actuarial probability of relapse in patients who responded to conventional
      salvage therapy before BMT was only 18% after allogenic BMT compared with 46%
      after autologous BMT. However, the actuarial probability of event-free survival
      at 4 years was the same, 47% versus 41%, for patients with responsive lymphomas
      who received allogeneic and autologous transplants, respectively (P = .8). The
      beneficial antitumor effect of allogeneic BMT was offset by its higher transplant
      related mortality (P = .01), largely resulting from graft-versus-host disease.
      Allogeneic BMT appears to induce a clinically significant graft-versus-lymphoma
      effect. The magnitude of this effect is similar to that reported against
      leukemias.

PMID- 1991175
TI  - Use of the polymerase chain reaction to monitor the effectiveness of ex vivo
      tumor cell purging.
AB  - The polymerase chain reaction (PCR) was used to detect residual malignant disease
      before and after ex vivo purging with monoclonal antibodies and complement or
      immunomagnetic treatment of BM samples contaminated with known numbers of
      t(14;18)-carrying tumor cells. Sensitivity of the PCR was demonstrated by
      detecting a specific t(14;18) amplification product in DNA extracted from a
      preparation consisting of one tumor cell among 10(5) normal cells. When BM
      contaminated with 1% to 5% t(14;18)-carrying cells from the B-cell lymphoma line
      SU-DHL-4 was subjected to two rounds of anti-B-cell pool of antibodies and
      complement (Ab-C) treatment a 3- to 4-log reduction of the pretreatment PCR
      signal was observed. A similar log-cell kill was detected using an independent
      clonogenic assay confirming the utility of the PCR approach. BM contaminated with
      a second B-cell lymphoma cell line, OCI-Ly8, was more resistant because a third
      cycle of Ab-C treatment was required to obtain a similar reduction in the PCR
      signal. A similar 4 logs of tumor cell removal was obtained using anti-B-cell
      antibodies conjugated to magnetic beads. These studies demonstrate that the
      t(14;18) PCR can be used to detect levels of tumor cells as low as 0.001%. This
      approach can be used to determine the effectiveness of BM purging in patients
      undergoing autologous BM transplantation as well as to assess the biologic role
      of minimal marrow disease.

PMID- 1991176
TI  - Syngeneic and allogeneic bone marrow engraftment after total body irradiation:
      dependence on dose, dose rate, and fractionation.
AB  - Murine bone marrow chimera models were used to assess the efficacy of host total
      body irradiation (TBI) given at different doses, dose rates, and fractionation
      schemes in providing for engraftment of syngeneic and allogeneic bone marrow. B6
      Hbbd congenic and LP mice, respectively, were used as donors (10(7) bone marrow
      cells) for syngeneic and allogenic (H-2 compatible) transplantation in standard
      B6 recipients. Stable marrow chimerism was determined from host and donor stem
      cell-derived hemoglobin phenotypes (Hbbs and Hbbd) on gel electrophoresis at 3
      months posttransplant. Partial engraftment of syngeneic marrow was seen at single
      doses as low as 2 Gy, with the donor component increasing steadily with
      increasing TBI dose to a level of 100% at 7 Gy. Immunologic resistance of the
      host appeared to prevent allogeneic engraftment until 5.5 Gy. A very steep
      radiation dose response was then observed so that the level of chimerism with 6
      Gy and above became comparable with syngeneic engraftment. Low dose rate (5 cGy
      minute-1) and fractionated TBI required higher total doses for equivalent
      engraftment (radiation dose-sparing) in both syngeneic and allogenic bone marrow
      transplantation. This displacement in the dose-response curve on fractionation
      was seen with interfraction intervals of 3 and 6 hours. A further dose-sparing
      effect was observed on extending the interval to 18 and 24 hours, but only for
      allogeneic transplantation, and may therefore be related to recovery of immune
      mediated graft resistance. The involvement of multiple target cell populations in
      determining allogenic engraftment rendered the application of the linear
      quadratic model for radiation cell survival problematic in this case. The
      recovery in dose when low dose rate and 6-hour interfraction intervals were
      applied in either syngeneic or allogeneic BMT is consistent with appreciable sub
      lethal damage repair in the primitive self-renewing stem cell population of the
      host marrow. These results contrast with the poor repair capacity of the 11-day
      spleen colony-forming units (CFUs) population after fractionated irradiation and
      support the notion that ablation of early stem cells in the pre-CFUs compartment
      is essential for long-term marrow engraftment.

PMID- 1991177
TI  - Alpha-interferon for polycythemia vera.

PMID- 1991178
TI  - HIV infected haemophiliacs settle.

PMID- 1991179
TI  - Contribution of general practitioners to hospital intrapartum care in maternity
      units in England and Wales in 1988.
AB  - OBJECTIVE: To ascertain the contribution of general practitioners to hospital
      intrapartum care in 1988. DESIGN: Confidential postal questionnaire. SETTING: All
      maternity units in England and Wales. MAIN OUTCOME MEASURES: Type of general
      practitioner unit (if any); number of bookings, transfers, and deliveries by
      general practitioners; participation of general practitioners in the policy and
      audit of the unit. RESULTS: 277 (93%) of 297 units replied. Of 611,644
      deliveries, 36,043 (5.9%) were under general practitioner care. In all, 228 units
      permitted general practitioners to book women under their sole care: 65 were
      isolated, 29 alongside, and 134 integrated general practitioner units. Alongside
      units had significantly more bookings (568), antenatal transfers (69),
      intrapartum transfers (86), and deliveries (387) compared with isolated units
      (185, 18, 16, and 125, respectively) and integrated units (106, 18, 18, and 52)
      (p less than 0.001 for all differences). The percentage of women booked by
      general practitioners transferred either before or during labour was independent
      of both the type of unit and the number of general practitioner bookings. General
      practitioners in consultant units were significantly less likely to attend
      meetings reviewing perinatal mortality (p less than 0.01), and these units were
      less likely to have any form of general practitioner-consultant liaison committee
      (p less than 0.001) compared with general practitioner units as a whole. Compared
      with those in isolated and alongside units, general practitioners in integrated
      units were less likely to have taken part in deciding the unit's booking policy
      (p less than 0.01) and consultants more likely to be the final determinant of
      whether a general practitioner should be permitted to practice within the unit (p
      less than 0.001). CONCLUSIONS: Both the number of deliveries booked by general
      practitioners and the number of isolated general practitioner units have fallen.
      Transfer from general practitioner to consultant care was independent of the
      general practitioner unit's caseload or the type of unit. General practitioner
      units differ from consultant units in important ways and differ among themselves
      as well. Except in remote areas, alongside units may be the ideal type of unit to
      encourage general practitioners to continue to provide intrapartum care.

PMID- 1991180
TI  - Occurrence and repetition of hospital admissions for accidents in preschool
      children.
AB  - OBJECTIVES: To examine trends over time in the rates of admission to hospital for
      accidents of preschool children and to study patterns of repeated admissions for
      accidents in these children. DESIGN: Analysis of linked, routine abstracts of
      hospital inpatient records for accidents. SETTING: Six districts in the Oxford
      Regional Health Authority covered by the Oxford record linkage study. SUBJECTS:
      Records for 19,427 children aged 5 years and under at the time of first recorded
      admission to hospital. MAIN OUTCOME MEASURE: Number of admissions to hospital.
      RESULTS: Records were analysed in three groups: person based annual admission
      rates were calculated for each calendar year; each child's first recorded
      admission in 1976-85 was identified, and the child's record was followed up by
      linkage for one year from that admission; each child's first recorded admission
      in 1976-81 was identified and followed up for five years. Overall, 19,427
      children from an average annual resident population of 163,000 children in 1976
      86 had 20,657 admissions for accidents before they were 6 years of age. Of these
      admissions 13,983 were for injuries, 5717 for poisonings, and 957 for burns.
      Admission rates declined after 1976 for poisoning, but no substantial changes
      over time were found in admission rates for injuries or burns. A total of 17,724
      children were followed up for one year and 10,889 for five years; 470 (2.6%) of
      the children who were followed up for one year and 926 (8.5%) of those followed
      up for five years had at least one further admission for an accident. Of those
      followed up for one year the 4 and 5 year old children were least likely and
      those under 1 and 1 year old were most likely to have a further admission for an
      accident. The number of children who had more than one accident was greater than
      would be expected if accidents were random occurrences. Those who had a poisoning
      at first admission were more likely to have another poisoning than an injury or
      burn; and those who had a burn at first admission were more likely to have
      another burn. CONCLUSIONS: Hospital admissions for accidents in children are
      common: on average 1 child in 88 in this population was admitted each year.
      Multiple admissions are uncommon but none the less occur more often than would be
      expected by chance.

PMID- 1991181
TI  - Primary medical treatment in breast cancer.

PMID- 1991182
TI  - Cigarette smoking and rate of gastric emptying: effect on alcohol absorption.
AB  - OBJECTIVE: To examine the effects of cigarette smoking on alcohol absorption and
      gastric emptying. DESIGN: Randomised crossover study. SETTING: Research project
      in departments of medicine and nuclear medicine. SUBJECTS: Eight healthy
      volunteers aged 19-43 who regularly smoked 20-35 cigarettes a day and drank small
      amounts of alcohol on social occasions. INTERVENTIONS: Subjects drank 400 ml of a
      radiolabelled nutrient test meal containing alcohol (0.5 g/kg), then had their
      rates of gastric emptying measured. Test were carried out (a) with the subjects
      smoking four cigarettes an hour and (b) with the subjects not smoking, having
      abstained for seven days or more. The order of the tests was randomised and the
      tests were conducted two weeks apart. MAIN OUTCOME MEASURES: Peak blood alcohol
      concentrations, absorption of alcohol at 30 minutes, amount of test meal emptied
      from the stomach at 30 minutes, and times taken for 50% of the meal to leave the
      proximal stomach and total stomach. RESULTS: Smoking was associated with
      reductions in (a) peak blood alcohol concentrations (median values in non-smoking
      versus smoking periods 13.5 (range 8.7-22.6) mmol/l v 11.1 (4.3-13.5) mmol/l),
      (b) area under the blood alcohol concentration-time curve at 30 minutes (264 x
      10(3) (0-509 x 10(3)) mmol/l/min v 140 x 10(3)) (0-217 x 10(3) mmol/l/min), and
      (c) amount of test meal emptied from the stomach at 30 minutes (39% (5-86%) v 23%
      (0-35%)). In addition, smoking slowed both the 50% gastric emptying time (37 (9
      83) minutes v 56 (40-280) minutes) and the intragastric distribution of the meal.
      There was a close correlation between the amount of test meal emptied from the
      stomach at 30 minutes and the area under the blood alcohol concentration-time
      curve at 30 minutes (r = 0.91; p less than 0.0001). CONCLUSION: Cigarette smoking
      slows gastric emptying and as a consequence delays alcohol absorption.

PMID- 1991183
TI  - Follow up after transurethral resection of prostate: who needs it?

PMID- 1991184
TI  - Hypothermia: dead or alive?

PMID- 1991185
TI  - Immunisation state of young children admitted to hospital and effectiveness of a
      ward based opportunistic immunisation policy.
AB  - OBJECTIVE: To study the need for and effectiveness of a ward based opportunistic
      immunisation policy. DESIGN: A six month prospective study. SETTING: An acute
      medical paediatric ward of an inner city teaching hospital. SUBJECTS: 296
      children admitted to the ward who lived within Central Manchester Health
      Authority boundaries and were aged from 5 months to 6 years. MAIN OUTCOME
      MEASURES: Completion of immunisation schedule appropriate for age. RESULTS: 56
      children were three or more months behind with immunisations. The parent's
      history was not reliable for 18 children. Accessing health authority immunisation
      records was not difficult. The main reasons for falling behind were the mobility
      of the families (15 children), lack of motivation (14), and frequent minor
      illnesses (9). 40 children were immunised before discharge, but three could not
      be because of valid contraindications. Of the 16 children requiring more
      immunisations after discharge, only four obtained them at the correct time and
      five children not at all. CONCLUSION: An opportunistic immunisation policy is an
      important means of immunising a vulnerable group of children who would often
      default on routine immunisations, and such policies should operate whenever
      possible. Our ward based policy can achieve immunisation of three quarters of
      possible children without change or inconvenience to the daily ward work, but
      efficacy relies on adequate levels of enthusiastic staff. The system can be
      improved by having accurate and updated immunisation records available in the
      hospital, and by encouraging nursing staff to participate.

PMID- 1991186
TI  - The NHS observed. Navigating the seas of change.

PMID- 1991187
TI  - Means tested benefits.

PMID- 1991188
TI  - Cyclosporin: use outside transplantation.

PMID- 1991189
TI  - Guidelines for writing papers.

PMID- 1991190
TI  - Breast prostheses.

PMID- 1991191
TI  - Should religious circumcisions be performed on the NHS.

PMID- 1991192
TI  - Fast neutron treatment for squamous cell carcinoma.

PMID- 1991193
TI  - Home treatment for acute psychiatric illness.

PMID- 1991194
TI  - Child health computing.

PMID- 1991195
TI  - Aerobic work capacity in chronic fatigue syndrome.

PMID- 1991196
TI  - Fatigue among general practice attenders.

PMID- 1991197
TI  - Prediction of hip fracture in elderly women.

PMID- 1991199
TI  - HIV infection in women.

PMID- 1991198
TI  - The yellow card: mark II.

PMID- 1991200
TI  - Colitis associated with ibuprofen.

PMID- 1991201
TI  - HIV and surgeons.

PMID- 1991202
TI  - Incidence of advanced renal failure.

PMID- 1991203
TI  - Organ donation in a neurosurgical unit.

PMID- 1991204
TI  - Tubal pregnancy.

PMID- 1991205
TI  - New prison health service.

PMID- 1991206
TI  - Early diagnosis of acute myocardial infarction.

PMID- 1991207
TI  - Safety and health in the construction industry.

PMID- 1991208
TI  - Aspects of ankylosing spondylitis.

PMID- 1991210
TI  - Can exercise prevent osteoporosis?

PMID- 1991209
TI  - Serological evidence of infection with Helicobacter pylori may predict
      gastrointestinal intolerance to non-steroidal anti-inflammatory drug (NSAID)
      treatment in rheumatoid arthritis.
AB  - Specific circulating antibodies to the spiral gastric organism, Helicobacter
      pylori (HP) were detectable in 43% of 68 patients with rheumatoid arthritis by
      complement fixation test (CFT) and enzyme-linked immunosorbent assay (ELISA), a
      frequency comparable with that of a normal, age-matched population. Presence of
      these antibodies correlated strongly with a previous history of peptic ulcer
      disease (PUD) and to the severity of NSAID-related dyspeptic symptoms, the latter
      often leading to multiple drug intolerance. This contrasts with short term,
      prospective NSAID toxicity data, which show little relationship between
      ulceration and HP carriage. This result suggests, however, that HP may have a
      definite role in the pathogenesis of symptomatic PUD associated with more chronic
      NSAID usage, and may have important implications for ulcer prophylaxis in these
      patients.

PMID- 1991212
TI  - The prevalence of rheumatoid arthritis in the Sultanate of Oman.
AB  - One thousand nine hundred and twenty-five Omani adults aged 16 and over were
      studied in a house-to-house survey in representative areas of Oman. Seven cases
      (five female) are described who satisfied the 1987 ARA criteria for rheumatoid
      arthritis (RA), indicating a prevalence of 3.6 per thousand adults. Adjusted for
      the population structure, the prevalence was 8.4 per thousand adults.
      Complementary data are also presented on cases of RA ascertained by special
      screening clinics in rural health centres and by hospital rheumatology clinics.
      In all parts of the study, cases of RA were less often seropositive than in
      European populations which may account for the lower prevalence of erosive
      disease.

PMID- 1991211
TI  - Transferrin C subtypes in patients with rheumatoid arthritis.
AB  - Transferrin (Tf) subtypes were investigated in 128 patients with rheumatoid
      arthritis (RA) and the frequencies of TfC subtypes were compared with the results
      in normal individuals. The frequencies of the Tf genes: C1, C2, C3, D1, and D2
      were 0.4765, 0.3867, 0.0742, 0.0390 and 0.0234, respectively. The frequency of
      TfC2 gene was significantly higher in these patients (0.3867) compared to the
      value in the control group (C2 = 0.247). The relative risk of RA in association
      with TfC1C2 type was 2.0, while it was 0.18 in association with TfC1C1 type and
      the results were statistically significant. This paper confirms the significant
      association between TfC2 and RA. Furthermore, it appears from our results that
      TfC1 homozygous phenotype is protective for the development of RA. The results
      are discussed in the light of earlier suggestions that the TfC2 subtype confers
      an increased risk of cellular damage by enhancing hydroxyl radical formation,
      although it is possible that there exists a genetic linkage of Tf variant to some
      other locus which is influencing susceptibility to RA.

PMID- 1991213
TI  - Clinical assessment of ankylosing spondylitis: a study of observer variation in
      spinal measurements.
AB  - Twenty-two measurements repeated non-sequentially on each of 10 patients by five
      observers were undertaken to determine their reliability for routine clinical
      use. Measurements without significant inter-observer variation or with a
      coefficient of reliability greater than 0.70 were cervical rotation, cervical
      lateral flexion, tragus to wall distance, fingertip to floor distance on sagittal
      and lateral flexion, C7 to iliac crest line distraction and modified Schober
      index. It is concluded that many of the currently used measurements are either
      statistically unreliable or clinically unhelpful in mild or moderate ankylosing
      spondylitis. The most clinically useful were cervical rotation using a
      protractor, cervical lateral flexion using a goniometer, thoracolumbar flexion as
      the C7 to iliac crest line distraction, thoracolumbar lateral flexion as the
      fingertip to floor distance and the modified Schober index.

PMID- 1991214
TI  - What is your policy for weaning polymyalgia rheumatica patients from
      corticosteroids after 2 years? How do you know when to stop the process, if at
      all?

PMID- 1991215
TI  - Septic arthritis as a non-surgical complication in rheumatoid arthritis: relation
      to disease severity and therapy.
AB  - More aggressive therapy including cytotoxic drugs is increasingly used in the
      treatment of rheumatoid arthritis (RA), and may confer increased susceptibility
      to infections. Septic arthritis is one infectious complication known to be
      overrepresented in RA. We studied the impact of disease severity and medication
      in a group of nine RA patients with proven septic arthritis, excluding those
      occurring as a complication of orthopaedic surgery. Two control groups were used
      for comparison. The septic arthritis patients were functionally more
      incapacitated and more often treated with cytotoxic drugs. Six of the nine septic
      arthritis patients had received an intra-articular injection into the infected
      joint within 3 months prior to the onset of the septic arthritis. Only one of
      these occurred immediately after arthrocentesis. The annual frequency of septic
      arthritis was approximately 0.2%. During the 4-year period studied the frequency
      was 0.5%. When related to the number of glucocorticosteroid injections, a
      frequency of 1 per 2000 injections was found when late septic arthritis was
      included. The high frequency of delayed septic arthritis after intra-articular
      glucocorticosteroid administration should alert physicians to this complication.

PMID- 1991216
TI  - Local injection treatment of tennis elbow--hydrocortisone, triamcinolone and
      lignocaine compared.
AB  - Corticosteroid injections are the mainstay of treating tennis elbow even though
      their effectiveness has not been well established by controlled studies. A survey
      of consultant rheumatologists confirmed a widespread preference for this
      treatment but they varied in their choice of steroid dose and preparation. We
      examined the value of some practices by comparing local injections of 2 ml 1%
      lignocaine with either 10 mg triamcinolone or 25 mg hydrocortisone made up to 2
      ml with 1% lignocaine (Study 1). The investigation was conducted double blind.
      Within the first 8 weeks, pain relief was greater for triamcinolone than
      hydrocortisone although the differences were not statistically significant. The
      response to both steroid preparations was significantly better than for
      lignocaine up to this point but at 24 weeks, the degrees of improvement were
      similar for all three groups and many patients still had pain. Relapse was
      common. In a separate but similarly designed study, triamcinolone 10 mg was
      compared with 20 mg of the same agent. Improvements of pain were similar and
      followed the same time scale. Post-injection worsening of pain occurred in
      approximately half of all steroid treated patients in both studies and this was
      sometimes severe and persistent. It was less frequent amongst those given
      lignocaine alone. Skin atrophy was reported in all groups but was more frequent
      amongst those given triamcinolone in Study 1. In conclusion, more rapid relief of
      symptoms was achieved with 10 mg triamcinolone than with 25 mg hydrocortisone or
      lignocaine alone and there was less needed to repeat injections. Results obtained
      with 20 mg triamcinolone were similar to those of the smaller dose.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1991217
TI  - The development and use of Patient Knowledge Questionnaire in rheumatoid
      arthritis.
AB  - A multi-choice Patient Knowledge Questionnaire (PKQ) was developed for use with
      patients with rheumatoid arthritis (RA). Test/re-test was used to test its
      stability (r = 0.81), and Kuder Richardson formula 20 (r = 0.72) for internal
      consistency. Seventy randomly selected RA patients then completed the PKQ in a
      rheumatology out-patient clinic of a large teaching hospital. There was a wide
      variation in total scores ranging from 3 to 28 out of 30. Total scores correlated
      with years of general education (P less than 0.05) but not with disease duration
      or age. Sixty-two per cent of patients knew that the cause of RA is, as yet,
      unknown but 27% thought it could be caused by injury and 11% by cold damp
      weather. Fifty-two per cent had no idea why they had blood tests. All but four
      patients were taking some form of medication but there was widespread confusion
      about disease-modifying drugs and non-steroidal anti-inflammatory drugs (NSAIDs).
      Exercise was reasonably well understood but many patients were unable to
      differentiate between methods of energy conservation and joint protection. This
      study highlights the need for careful individual knowledge assessment by use of
      tools such as the PKQ and effective patient education programmes.

PMID- 1991218
TI  - Immunogenetic heterogeneity in rheumatoid disease as illustrated by different MHC
      associations (DQ, Dw and C4) in articular and extra-articular subsets.
AB  - Genetic variants at DRB1 (Dw subtypes), DQB, and C4 loci were compared in
      rheumatoid disease subjects with or without the extra-articular feature of
      Felty's syndrome or major vasculitis. DR4 positive subjects with rheumatoid
      arthritis alone showed no preferential associations with DQB or Dw variants or
      with C4 null alleles. Felty's subjects showed associations with the DQB encoded
      DQw7 allele and with the C4B null allele but no preferential associations with
      any Dw subtype of DR4. By contrast DR4 +ve rheumatoid-vasculitic subjects showed
      associations with the Dw14 as well as with DQw7 and the C4A null allele. These
      different MHC associations in different clinical disease subsets show that
      rheumatoid disease is immunogenetically heterogeneous and suggest that MHC genes
      outside the DRB1 locus may also influence susceptibility or modify expression of
      the rheumatoid disease process.

PMID- 1991219
TI  - Review of UK data on the rheumatic diseases--5. Ankylosing spondylitis.

PMID- 1991220
TI  - Higher incidence of carpal tunnel syndrome in oophorectomized women.
AB  - To determine whether the hormonal changes of the menopause are related to the
      onset of carpal tunnel syndrome (CTS), 53 healthy women, younger than 44 years,
      and subjected to bilateral oophorectomy between 1 and 4 years before the study,
      were evaluated. Seventy healthy menstruating women matched for age were used as
      controls. In those complaining of symptoms and presenting signs suggestive of
      CTS, sensory and motor nerve conduction studies were done. In the oophorectomized
      group, 17 of 53 (32%) had clinical CTS, while only seven of 70 of the control
      group (10%) did so (relative risk for the oophorectomized group = 4.25; 95%
      confidence intervals 1.47 and 12.61). The nerve conduction studies were abnormal
      in 14 of 16 oophorectomized women (87.5%), and in only one of seven of the
      control group (14.2%; P less than 0.002). Symptoms tended to be milder in the
      controls. Symptoms developed in the first year after oophorectomy in 14 of the 17
      women with CTS. This suggests that women develop CTS after oophorectomy more
      frequently than controls.

PMID- 1991221
TI  - Postgraduate training in rheumatology.

PMID- 1991222
TI  - Laryngeal and ear involvement in rheumatoid arthritis in north India.

PMID- 1991223
TI  - Interpretation of therapeutic trials.

PMID- 1991224
TI  - Bilateral iliopsoas bursitis in rheumatoid arthritis.

PMID- 1991225
TI  - Late onset ankylosing spondylitis--a distinct disorder?

PMID- 1991226
TI  - Joint manifestations of Lyme disease in Spain.

PMID- 1991227
TI  - The use of infra-red thermography in a rheumatology unit.

PMID- 1991228
TI  - Rheumatoid arthritis: fish oil? Or snake oil?

PMID- 1991229
TI  - Effects of methotrexate on clinical and immunological parameters in refractory
      rheumatoid arthritis: a prospective study.

PMID- 1991230
TI  - Mianserin as a cause of arthritis.

PMID- 1991231
TI  - Severe thrombocytopenia associated with auranofin: evidence for immunological
      mechanism with peripheral destruction in the spleen.

PMID- 1991232
TI  - 1992 and all that.

PMID- 1991233
TI  - Osteoarthritis: clinical and research perspective.

PMID- 1991234
TI  - The cartilage collagens and joint degeneration.

PMID- 1991235
TI  - The inter-relationship of facet joint osteoarthritis and degenerative disc
      disease.

PMID- 1991236
TI  - Molecular markers of processes in cartilage in joint disease.

PMID- 1991237
TI  - Metalloproteinases and tissue damage.

PMID- 1991238
TI  - Chondrocyte responses in cartilage and in experimental osteoarthritis.

PMID- 1991239
TI  - Immunoglobulin gene expression in systemic rheumatic diseases.

PMID- 1991240
TI  - The potential role of B-lymphocytes in the pathogenesis of rheumatoid arthritis.

PMID- 1991241
TI  - Animal models: insights into osteoarthritis (OA) provided by the cruciate
      deficient dog.

PMID- 1991242
TI  - Antigen presentation in joints in the pathogenesis of arthritis.

PMID- 1991243
TI  - Molecular definition of the Ro(SSA) particle(s): a frequent target of
      autoimmunity in systemic lupus erythematosus and Sjogren's syndrome.

PMID- 1991244
TI  - The immune response to autoantigens and viruses in rheumatic disease.

PMID- 1991245
TI  - Is tolerance therapy a plausible possibility?

PMID- 1991246
TI  - Cytokine expression in rheumatoid arthritis.

PMID- 1991247
TI  - Cytomorphologic, immunocytochemical, and nucleic acid flow cytometric study of 50
      lymph nodes by fine-needle aspiration. Comparison with results obtained by
      subsequent excisional biopsy.
AB  - Fifty patients with clinically suspected or previous diagnosis of lymphoma
      underwent fine-needle aspiration (FNA) and subsequent excisional biopsy of their
      lymph nodes. Results of cytologic diagnosis made from the direct smears in
      conjunction with immunocytochemical study of cytospin preparations and nucleic
      acid flow cytometric study (FCM) were compared with the results obtained from
      histologic sections, cryostat-immunohistochemical study, and nucleic acid FCM
      performed on resected lymph nodes. This study demonstrates (1) results of
      immunocytochemical and DNA-FCM analysis of FNA-derived material are comparable in
      the majority of cases to those obtained from surgical specimens, (2)
      immunostaining of cytospin preparations for immunoglobulin (Ig) gives less
      background staining and in certain cases is easier to interpret than when
      performed on frozen sections, and (3) monotypia in FNA in conjunction with
      cytomorphologic study is 100% specific for lymphoma, and polytypic staining for
      Ig does not exclude HD, T-cell lymphoma, or B-cell malignancy focally involving a
      lymph node.

PMID- 1991248
TI  - Fine-needle aspiration evaluation of lymphoproliferative lesions in human
      immunodeficiency virus-positive patients. A multiparameter approach.
AB  - Forty-six fine-needle aspirates of lymphoproliferative lesions from 31 human
      immunodeficiency virus (HIV)-positive patients were reviewed using
      cytomorphologic, immunocytochemical, flow cytometric (FCM), cytogenetic, and
      molecular studies. There were 29 lymphomas (15 small non-cleaved cell [SNCL], 11
      large cell [LCL], one small lymphocytic, and two Hodgkin's), 14 reactive
      hyperplasias, and three "atypical lymphoid proliferations." The reactive
      hyperplasias were characteristically polymorphic and polyclonal lymphoid
      populations; six of seven were diploid on FCM, the seventh was hypodiploid.
      Higher proliferative indices (mean, 11.6%) and higher RNA indices (mean, 1.2)
      characterized this subgroup compared with published reactive lymphoid
      hyperplasias from patients without HIV positivity. Aspirates of SNCL showed
      monotonous populations of intermediate-sized cells except in one patient where a
      giant cell syncytial variant occurred. Nine of 13 SNCL aspirates showed light
      chain restriction. JH rearrangement revealed B-cell lineage in one aspirate in
      which immunocytochemical study was negative for Kappa, lambda, B1, and Leu-4.
      Nine of 12 SNCL were diploid; the mean proliferative index was 25.6% and the mean
      RNA index 2.3. Chromosomal translocations involving the c-myc locus were
      demonstrated in five of seven SNCL aspirates karyotyped. Five of eight LCL showed
      light chain restriction the remaining three showed null cell phenotype. Large
      cell lymphomas were diploid on tetraploid with the mean proliferative index of
      22.0% and mean RNA index of 2.2. One of two LCL aspirates karyotyped demonstrated
      c-myc translocation. Despite the multiparameter approach, a definitive diagnosis
      could not be reached in three aspirates.

PMID- 1991250
TI  - Thymic carcinoma. A clinicopathologic study of 60 cases.
AB  - The clinicopathologic features of 60 patients with thymic carcinoma were studied.
      Patients ranged in age from 10 to 76 years (mean, 46), of whom 24 were females
      and 36 were males. Overall survival at 1, 3, and 5 years was 56.6%, 40%, and
      33.3%, respectively. The following morphologic features were correlated with
      survival: type of tumor margins; presence or absence of a lobular growth pattern;
      nuclear atypia; necrosis; mitotic activity; and histologic tumor type and grade.
      Eighty eight percent of patients with poorly circumscribed/infiltrating neoplasms
      died of their tumors as compared with 16.6% of patients with well-circumscribed
      neoplasms (P less than 0.0000). Of patients whose tumors had mitotic counts
      exceeding 10/10 high-power fields (HPF), 84.3% died, as compared with 21.4% of
      patients with lower mitotic counts (P less than 0.0000). Of patients whose tumors
      showed lack of lobular growth pattern, 91.6% died, as compared with 29% of those
      whose tumors had a lobular growth pattern (P less than 0.0000). Finally, 84.6% of
      patients whose tumors displayed a high-grade histology (lymphoepithelioma-like
      carcinoma, small cell/neuroendocrine carcinoma, clear cell carcinoma, sarcomatid
      carcinoma, and anaplastic/undifferentiated carcinoma) died of tumor, as compared
      with 0% of patients whose tumors were of low-grade histology (well-differentiated
      squamous carcinoma, mucoepidermoid carcinoma, and basaloid carcinoma) (P less
      than 0.0000). Evaluation of the various treatment modalities used to treat these
      patients did not yield any statistically significant correlations with survival.
      Two clinically distinct groups of patients were identified: one after a
      relatively favorable clinical course with long survival, and one after a rapidly
      fatal outcome. The morphologic features of the tumors in these patients
      correlated well with their clinical behavior; histologic type (and the grade to
      which it was assigned) constituted the most reliable and important predictor of
      prognosis.

PMID- 1991249
TI  - Juvenile (embryonal and alveolar) rhabdomyosarcoma of the head and neck in
      adults. A clinical, pathologic, and immunohistochemical study of 12 cases.
AB  - Sites in the head and neck region (orbit, nasopharynx, nasal cavity, etc.) are
      among the most frequent locations for juvenile (embryonal and alveolar)
      rhabdomyosarcomas in patients younger than 15 years; however, comparable
      neoplasms in adults are very uncommon. A clinicopathologic and
      immunohistochemical study of 12 juvenile rhabdomyosarcomas in patients between
      the ages of 18 and 36 years is presented. There was a female:male ratio of 2:1.
      The orbit with or without contiguous paranasal sinus involvement, nasal cavity,
      sphenoid sinus, middle ear, and soft tissues of the neck and preauricular region
      were the primary sites. Seven tumors involved a parameningeal site and eight
      cases were alveolar rhabdomyosarcomas which together contributed to the adverse
      outcome. Only two patients were long-term, disease-free survivors. Six patients
      have died of tumor and two others are alive with persistent disease.
      Immunohistochemical study in 11 cases demonstrated reactivity for vimentin and
      muscle-specific actin (HHF-35) and desmin in ten cases. Juvenile rhabdomyosarcoma
      rarely presents in the head and neck of adults but should be considered in the
      differential diagnosis of a small cell neoplasm in patients during the third and
      fourth decades of life.

PMID- 1991251
TI  - A comparative analysis of three different techniques for the detection of breast
      cancer cells in bone marrow.
AB  - Three different methods, morphologic, immunocytochemic, and fluorescence
      activated cell sorter (FC) analysis, were compared with respect to their
      efficiency in detecting breast cancer cells in bone marrow. In the first series
      of experiments, the three techniques were compared using bone marrow cells
      artificially mixed with a known amount of breast cancer cells, whereas in a
      second series bone marrow from breast cancer patients with bone metastases were
      used. The following results were obtained: When mixtures of the first series were
      analyzed, FC analysis detected from 1% to 10% of breast cancer cells in bone
      marrow (0.2% was a border line value), the morphologic method detected from 0.05%
      to 10%, and the immunocytochemic method, which was clearly superior, detected
      breast cancer cells in all mixtures (from 0.00025% to 10%). It was noted that,
      with both the morphologic and immunocytochemic methods, the percentage of breast
      cancer cells detected was 2 to 360 times higher than the percentage of added
      cells, and enrichment was inversely proportional to the percentage of added
      cells. This result could be a result of different separation of cells during
      centrifugation due to the different density of breast cancer cells. The
      superiority of the immunocytochemic method was confirmed in the second series of
      experiments.

PMID- 1991252
TI  - Microinvasive carcinoma of the uterine cervix (International Federation of
      Gynecology and Obstetrics Stage IA).
AB  - In 1985 the International Federation of Gynecology and Obstetrics (FIGO)
      subdivided Stage IA cervical cancer and specified metric criteria to demarcate
      Stage IA from Stage IB. Early stromal invasion (Stage IA1) denotes the first
      invasive protrusions of a carcinoma in situ into the stroma. Microcarcinomas
      (Stage IA2) are small cancers a number of orders of magnitude larger than Stage
      IA1 lesions and with a maximum depth of invasion of 5 mm and a maximum horizontal
      spread of 7 mm; larger lesions are classified as Stage IB. This study reviews 486
      patients previously classified as having Stage IA disease. This yielded 344 Stage
      IA1 and 101 Stage IA2 lesions; 41 cancers were reclassified as Stage IB. Three
      hundred nine, 89, and 38 patients were followed for greater than or equal to 5
      years. One (0.3%) patient with Stage IA1 disease re-presented with Stage IIB
      disease 12 years after conization. Five (5.6%) patients with Stage IA2 lesions
      developed invasive recurrences; three died. None of the 38 patients reclassified
      as having a Stage IB lesion, including 16 who were treated conservatively,
      developed a recurrence. The FIGO classification is not a guideline for treatment.
      Stage IA1 lesions can be treated conservatively, but treatment in Stage IA2 must
      be individualized. Risk factors such as vascular space involvement and confluency
      are of high sensitivity but low specificity.

PMID- 1991253
TI  - Idiopathic hypereosinophilic syndrome terminating as disseminated T-cell
      lymphoma.
AB  - The authors describe a case of idiopathic hypereosinophilic syndrome (HES)
      terminated as a T-cell lymphoma in a 3-year-old girl. The clinical course was
      chronic and characterized by chronic eczema, persistent peripheral blood
      eosinophilia, organomegaly, interstitial lung change, and pericarditis.
      Postmortem examination demonstrated a disseminated T-cell lymphoma involving the
      inguinal lymph node, liver, lung, and kidney. The findings of the current case
      suggest a possibility that certain abnormalities in this case of idiopathic HES
      per se may have triggered the development of malignant lymphoma, and it may
      represent a transition of idiopathic HES into a T-cell lymphoma. Other possible
      sequences are discussed. The development of T-cell malignancy in idiopathic HES
      in a girl is quite an unusual presentation.

PMID- 1991254
TI  - Hypersensitivity reactions to epipodophyllotoxins in children with acute
      lymphoblastic leukemia.
AB  - The incidence, clinical characteristics, and outcome of hypersensitivity
      reactions to teniposide (VM-26), etoposide (VP-16), or both were determined in
      108 children with acute lymphoblastic leukemia (ALL) treated with a contemporary
      regimen of intensive multiagent chemotherapy. Fifty (46%) of the 108 patients had
      one or more hypersensitivity reactions. The risk of any child having an initial
      reaction over the cumulative dose range studied was 52% (95% confidence limits,
      41% and 63%) for VM-26, compared with 34% (95% confidence limits, 24% and 44%)
      for VP-16. The risk of having an initial reaction to VM-26 or VP-16 was clearly
      related to the cumulative dose. This risk peaked at 1500 to 2000 mg/m2 for VM-26
      and at 2000-3000 mg/m2 for VP-16. All reactions were Type 1 reactions according
      to the Gell and Coombs classification, characterized by urticaria, angioedema,
      flushing, rashes, or hypotension, and 86% of reactions were of Grade 1 or 2
      severity according to standard criteria. There was no evidence of increasing
      clinical severity on repeated rechallenge with premedication, and no deaths
      occurred. The findings suggested that hypersensitivity reactions to
      epipodophyllotoxins in children with ALL are more common than previously
      reported, but only rarely constitute dose-limiting toxicity.

PMID- 1991255
TI  - Malignant glandular triton tumor.
AB  - A case of left brachial plexus-related malignant peripheral nerve sheath tumor
      showing neoplastic, glandular, and rhabdomyoblastic elements in a 39-year-old
      Chinese man is reported. The authors suggested that this tumor be termed a
      malignant glandular triton tumor in view of the presence of the
      adenocarcinomatous component. The patient had extensive local recurrence
      comprising mainly the Schwann spindle cells within a year after complete
      piecemeal removal and died 15 months later after the initial presentation. The
      natural behavior of this tumor, as in other reported cases of malignant triton
      tumor, is extremely aggressive, unlike malignant schwannoma or glandular
      malignant schwannoma. The histogenesis of this tumor is likely to be from
      primitive neural crest cells, Schwann's cell precursors, or metaplastic malignant
      Schwann's cells.

PMID- 1991256
TI  - The long-term effects of radiation therapy on patients with ovarian dysgerminoma.
AB  - A retrospective chart review and questionnaire study was undertaken to look at
      the long-term effects of radiation therapy in ovarian dysgerminoma patients.
      Forty-three patients and 55 controls responded to a questionnaire that detailed
      bowel, bladder, thyroid, menstrual, reproductive, sexual, and growth function.
      Statistically significant differences in the number of bowel movements were
      noticed when comparing patients with controls. The authors noticed no significant
      differences between cases and controls in bladder function. No thyroid disorders
      were attributable to mediastinal radiation therapy. Most patients with intact
      uteri bleed monthly on hormonal replacement. Three patients with a remaining
      ovary and uterus resumed menstrual function after substantial doses of
      abdominopelvic radiation therapy. No patients have conceived. The authors noticed
      a slight increase in dyspareunia in the treated group, but most patients were
      satisfied with their sexual function. One premenarchal patient exhibited a growth
      disorder.

PMID- 1991257
TI  - Expectant management of localized prostatic cancer.
AB  - Seventy-five patients with clinical Stage B histologically proven prostatic
      cancer accumulated over a 40-year period and receiving no therapy for at least 1
      year after histologic diagnosis were retrospectively reviewed. Twenty-nine
      patients had Stage B1 lesions, 37 had B2, and nine had B3 lesions; median follow
      up for these patients was 124, 120, and 96 months, respectively. Five ultimately
      received pelvic lymph node dissection with iodine-125 implantation, 23 had
      transurethral resection of the prostate, and 18 had endocrine therapy. Of those
      tumors which progressed, 18 of 19 (95%) B1, 26 of 29 (90%) B2, and four of four
      (100%) B3 lesions demonstrated local progression first. Six of 29 (21%) B1, 17 of
      37 (46%) B2, and two of nine (22%) B3 tumors developed recognized distant
      metastasis. Actuarial survival at 15 years was 67%, 39%, and 63% for patients
      with B1, B2, and B3 lesions, respectively. These data indicate the varied and
      potentially protracted course of patients with clinical Stage B prostatic cancer.

PMID- 1991258
TI  - Psychosocial adjustment in women with breast cancer.
AB  - There is a plethora of studies investigating psychosocial adjustment in women
      with breast cancer, its correlates, clinical course, and prognosis. These studies
      have been conducted with varying degrees of methodologic rigor. An assessment has
      been made of the quality of this existing evidence to identify from the best
      evidence the factors which predict the adjustment status of women with breast
      cancer. Studies have been reviewed, using methodologic standards for the critical
      appraisal of studies on prognosis, developed by Sackett and colleagues in the
      Department of Clinical Epidemiology and Biostatistics at McMaster University
      (Hamilton, Ontario, Canada). Few of the studies investigating psychosocial
      adjustment of women with breast cancer meet all of the criteria for reviewing
      studies of clinical course and prognosis. This review focuses the direction and
      methodologic rigor required in future investigations. In particular, studies are
      needed that employ prospective designs and that deliberately measure or control
      for the extraneous prognostic variables that may affect adjustment. Future
      investigations need to incorporate adequate precision in measurement so that
      measures of the psychosocial variables are objective, reliable, and valid.

PMID- 1991259
TI  - Prognosis of pregnancy-associated breast cancer.
AB  - The survival of patients with pregnancy-associated (PA) breast cancer is
      difficult to predict for two reasons: The combination is very rare, and the
      natural history of breast cancer that is not associated with pregnancy is
      intricate and varies among individuals. Valid data collection and analysis is
      problematic given that studies gather patients over many years. The charts of 56
      women with Stages I, II, and III breast cancer, who were pregnant or within 1
      year postpartum at the time of breast cancer diagnosis between 1960 and 1980,
      were analyzed. Patients with PA breast cancer were compared to nonpregnant women
      of comparable ages, who were treated at the same hospital, by the same
      physicians, and during the same period. Four patients were lost before 5-year
      follow-up, and one patient before 10-year follow-up. These five patients had
      distant metastases at the time they were lost to follow-up, and are considered to
      have died within that time. Across stages, patients with PA breast cancer have
      survival not significantly different from those patients with non-pregnancy
      associated (non-PA) breast cancer.

PMID- 1991260
TI  - Patient-controlled analgesic administration. A comparison of steady-state
      morphine infusions with bolus doses.
AB  - The authors have shown previously that bone marrow transplant (BMT) patients who
      self-administered bolus doses of morphine gained equal oral mucositis pain relief
      while using less drug compared with similar patients receiving morphine by staff
      controlled continuous infusion. In a follow-up study they compared the efficacy
      and side effects of morphine in two groups of marrow transplant patients who
      controlled their own analgesic administration either by conventional bolus-dose,
      patient-controlled analgesia (PCA) or by adjusting the rate of continuous
      morphine infusion to increase or decrease their plasma morphine concentration.
      Patients controlling their morphine infusion rates (pharmacokinetically based
      patient-controlled analgesia [PKPCA] group) obtained more relief from oral
      mucositis pain than did patients using conventional PCA. Patients in the PKPCA
      group used more morphine than PCA patients and achieved superior pain relief
      without significant increases in side effects (e.g., nausea, mood changes,
      sedation). The authors conclude that PKPCA improves the management of prolonged,
      severe pain in marrow transplant patients and that this approach to patient
      controlled analgesia may be useful in other types of persistent pain.

PMID- 1991262
TI  - Ultrasound-guided hepatic cryosurgery in the treatment of metastatic colon
      carcinoma. Preliminary results.
AB  - Cryosurgery, the in situ freezing of cancer, has been proposed in the past as a
      possible treatment for unresectable hepatic tumors. Its advantage lies in the
      fact that it is a very focal treatment sacrificing less normal tissue than
      surgical resection, allowing treatment of multiple lobes. Because cryosurgery
      does not affect large vessels, tumors in difficult locations, such as adjacent to
      the inferior vena cava (IVC), can be treated. With the use of intraoperative
      ultrasound to place the cryoprobes and monitor the freezing process, 18 patients
      with unresectable metastatic colon carcinoma confined to the liver were treated.
      Of the 18 patients treated, 4 (22%) are in complete remission as determined by
      computed tomography (CT) scans and carcinoembryonic antigen (CEA) levels, with a
      mean follow-up of 28.8 months. Four patients (22%) were not adequately treated at
      the time of cryosurgery. The number of lesions frozen in each patient ranged from
      1 to 12, with a mean of 6 lesions. Fourteen patients had bilobar disease; three
      patients had previous right lobectomies with recurrences in their remaining left
      lobes prior to cryosurgery, and one patient had unilobar disease. Mean survival
      of the 14 cases with recurrence was 21.4 months, with 2 of the 14 still alive.
      Ultrasound-guided hepatic cryosurgery appears to be an effective treatment for
      metastatic colon carcinoma to the liver that is unresectable (including patients
      with bilobar and multiple lesions). These preliminary results indicate that the
      procedure warrants further study.

PMID- 1991261
TI  - Combination hormonal therapy with tamoxifen plus fluoxymesterone versus tamoxifen
      alone in postmenopausal women with metastatic breast cancer. An updated analysis.
AB  - A randomized trial was performed to determine if therapy with tamoxifen (TAM)
      plus fluoxymesterone (FLU) was more efficacious than TAM alone for postmenopausal
      women with metastatic breast cancer. Patients failing TAM could subsequently
      receive FLU. The dose of both drugs was 10 mg orally twice daily. Objective
      responses were seen in 50 of 119 (42%) TAM patients and 64 of 119 (54%) TAM plus
      FLU patients (two-sided P = 0.07). Time to disease progression was better for TAM
      plus FLU (medians: 11.6 versus 6.5 months; Cox model, P = 0.03). Duration of
      response and survival were similar in the two treatment arms. Among 97 patients
      with estrogen receptor (ER) of 10 or greater and 65 years of age or older, there
      were highly significant advantages for treatment with TAM plus FLU in both
      response rate and time to progression. Of particular note is that in this patient
      group TAM plus FLU showed a survival advantage (Cox model, P = 0.05). Although
      these data require confirmation in a prospective randomized trial, they suggest
      that there is a substantive therapeutic advantage for TAM plus FLU over TAM alone
      in elderly women with ER of 10 fmol or greater.

PMID- 1991263
TI  - Sphincter preservation in rectal cancer by local excision and postoperative
      radiation therapy.
AB  - The authors report the preliminary results of 14 patients with localized, mobile,
      resectable rectal cancer treated with local excision and postoperative radiation
      therapy (RT). All had negative surgical resection margins and two received 5
      fluorouracil (5-FU). The median follow-up was 29 months (4-43 months). The 3-year
      actuarial survival was 88%. The incidence of local failure was 7% (only site of
      failure) and 21% (component of failure). The incidence of local failure increased
      with T stage (T1, 0/3 [0%]; T2, 1/7 [14%]; and T3, 2/4 [50%]) and tumor size
      (greater than 3 cm, 33%, versus less than or equal to 3 cm, 0%). Three patients
      developed local failure at 6, 15, and 21 months. Three underwent a salvage
      abdominoperineal resection and were locally controlled at 2 and 28 months
      following salvage surgery. One patient underwent an abdominoperineal resection
      for a clinically presumed local failure; however, no tumor was found in the
      specimen. Therefore, the 13 patients who either were initially locally controlled
      or underwent salvage or nonsalvage surgery had no evidence of disease in the
      pelvis at the time of last follow-up. Local excision and postoperative RT may be
      an alternative to standard surgery in selected cases. However, additional follow
      up and more experience are needed in order to determine if this approach will
      ultimately have local control and survival rates similar to those of a low
      anterior resection or an abdominoperineal resection.

PMID- 1991264
TI  - Treatment of advanced neuroblastoma with I-131 meta-iodobenzylguanidine.
AB  - From February 1986 to December 1988, 31 children with advanced pretreated
      neuroblastoma were treated with 131-I meta-Iodobenzylguanidine (131-MIBG).
      Thirteen children had been resistant to first-line therapy, three had suffered a
      local relapse, and fourteen had suffered a disseminated relapse without over bone
      marrow infiltration. One child was treated initially because of resistance to
      first-line therapy, and subsequently for a local relapse. A total of 72 courses
      of 131-MIBG was administered, with doses ranging from 2.8 to 6.0 GBq (median, 3.7
      GBq). One child received five courses, two four courses, 13 three courses, four
      two courses, and 12 one course of 131-MIBG. The most common toxic effect was
      thrombocytopenia, with a platelet level of less than 50,000/cmm occurring after
      19 of 60 evaluable courses. A leukocyte count less than 1000/cmm was seen only
      once. There were six major responses (two complete) lasting 4 to 9 months, and
      two minor responses lasting longer than 38 and 44 months. Responses were seen
      more commonly in children whose only lesion was a residual primary tumor and in
      children who had not been pretreated who experienced disseminated relapse.
      Further studies of the role of 131-I meta-Iodobenzylguanidine in treatment of
      neuroblastoma are needed.

PMID- 1991265
TI  - Predictors of physician nonadherence to chemotherapy regimens.
AB  - Physician nonadherence to cancer treatment regimens may diminish treatment
      efficacy and compromise clinical research. The influence of clinical,
      demographic, and psychosocial patient characteristics on physician adherence to
      breast cancer chemotherapy was investigated, as was the role of the clinician's
      attitudes concerning the chemotherapy. One hundred seven women recently diagnosed
      with breast cancer were followed for 26 weeks of treatment. Fifty-six (52%) of
      the patients experienced unjustified modification for at least one
      chemotherapeutic agent. Stepwise multiple regression revealed independent
      contributions of increased patient age, treatment setting (clinic versus academic
      or community private practice), and stage of disease to physician nonadherence.
      Regimen complexity, delay in seeking treatment, and presence of psychiatric
      disorder did not contribute, in general, to unjustified regimen modifications.
      Patient psychological and psychiatric factors, however, did influence prescribing
      behavior for vincristine. Physician awareness of factors contributing to
      unnecessary treatment modifications may reduce the frequency of such behaviors.

PMID- 1991267
TI  - Expression of class I and II human leukocyte antigens by thyrocytes and
      lymphocytic infiltration on human thyroid tumors. An immunofluorescence study.
AB  - Surgical thyroid sections from 30 papillary carcinomas (PC), six medullary
      carcinomas (MC), three anaplastic carcinomas (AC), two follicular carcinomas
      (FC), and 16 adenomas (AD) were examined with an indirect immunofluorescence
      technique employing different monoclonal antibodies to evaluate the expression of
      human leukocyte antigen (HLA)-A, B, C (Class I) and DR, DP, DQ (Class II) by
      thyrocytes, together with the phenotype and distribution of inflammatory cells.
      Ten PC and four FC were also investigated for the presence of intercellular
      adhesion molecule-1 (ICAM-1). In situ deposits of immunocomplexes and circulating
      thyroid autoantibodies were also evaluated. An increased expression of Class I
      antigens was found in all PC and FC, in 33% of MC and AC, and in 31% of AD. An
      anomalous expression of Class II antigens was observed in 70% of PC, in 50% of
      FC, in 33% of AC, in 19% of AD, and in none of the MC. Expression of DP or DQ was
      revealed only in a portion of the DR-positive glands. A reduction of microsomal
      autoantigen expression was found. No ICAM-1-positive thyrocytes were detected. A
      moderate T-lymphocytic infiltrate was noticed only in PC, where it was correlated
      with DR and DP and/or DQ coexpression. B-cells and natural killer cells were
      virtually absent. The authors speculate that the weak Class II antigens
      expression, together with the partial or complete loss in microsomal autoantigen
      and the absence of ICAM-1 by thyrocytes, may account for the limited engagement
      of immunocompetent cells observed in thyroid tumors.

PMID- 1991266
TI  - Platelet factor 4 mRNA expression in cells from a patient with megakaryoblastic
      crisis of chronic myelogenous leukemia.
AB  - A 61-year-old man with Philadelphia chromosome-positive chronic myelogenous
      leukemia developed megakaryoblastic leukemia. In the blast phase, his blast cells
      showed undifferentiated megakaryoblastic characteristics with no alpha-granules
      or demarcation membranes but with detectable platelet peroxidase (PPO) activity
      and surface glycoprotein (GP) IIb/IIIa. The patient has remained reasonably well
      for at least 12 months after blastic crisis, and 6-mercaptopurine alone has been
      effective in controlling leukocytosis and megakaryoblast proliferation. The
      expression of mRNA for platelet-specific proteins, such as GPIIb and platelet
      factor 4 (PF4), was studied in the patient's blast cells by the Northern blot
      analysis. Both GPIIb and PF4 mRNA were detected in the blast cells. Cytoplasmic
      maturation occurs later than the synthesis of the surface GP during megakaryocyte
      maturation. Therefore, PF4 mRNA expression should be a marker of mature
      megakaryoblasts. The PF4 mRNA expression in megakaryoblastic leukemia may
      indicate that a patient will have long survival and a good response to
      chemotherapy.

PMID- 1991268
TI  - Immunohistologic evaluation of parathyroid hormone-related protein in human lung
      cancer and normal tissue with newly developed monoclonal antibody.
AB  - With a newly developed monoclonal anti-PTHrP antibody, 4B3, the
      immunohistochemical localization of the parathyroid hormone-related protein
      (PTHrP) was studied on the formalin-fixed and paraffin-embedded sections of
      normal human tissues and various subtypes of lung cancer. Among normal epithelial
      tissues, keratinocytes in squamous epithelia, transitional and bronchial
      epithelia with squamous metaplasia, meningoepithelial cells, and mammary ductal
      cells with lactating changes showed positive immunoreactivity. Also, among
      endocrine tissues, cells in the parathyroid gland, pancreatic islets, adrenal
      cortex, pituitary gland, and testis were sporadically positive for PTHrP. These
      distribution patterns suggested that in a physiologic condition, PTHrP was
      closely related to keratinization and local secretion and/or the metabolism of
      calcium in specifically differentiated tissues. In lung cancer, however, PTHrP
      was detected in all cases of well-differentiated and moderately differentiated
      squamous cell carcinoma and in most cases of small cell carcinoma, irrespective
      of the patients' serum calcium level. However, PTHrP was not detected in two of
      five cases of poorly differentiated squamous cell carcinoma and in all cases of
      adenocarcinoma. Consequently, it was found that PTHrP was commonly produced by
      squamous cell carcinomas of the differentiated type, and that humoral
      hypercalcemia of malignancy could be induced when the PTHrP transgressed the
      homeostatic mechanisms.

PMID- 1991270
TI  - Advances in medical imaging for cancer diagnosis and treatment.
AB  - Over the last several decades, significant "new eyes" have been developed that
      improve the diagnosis, treatment, planning, and monitoring of human cancer:
      computer tomography (CT), magnetic resonance imaging (MRI) and spectroscopy
      (MRS), single photon emission computed tomography (SPECT), and positron emission
      tomography (PET). Innovative advances in both morphologic and functional imaging
      have led to a dramatic improvement in our ability to diagnose and monitor human
      cancer. Frequently, anatomic detail can be demonstrated in ways that exceed views
      at surgery, and functional biochemical imaging is being used to show the
      metabolic activity and receptor status of normal and pathologic states. In vivo
      functional and biochemical studies differentiate normal from neoplastic or
      nonviable tissue, and make it possible to measure progression or regression of
      the disease. Because physiologic changes often precede morphologic findings in
      many disease processes, the use of in vivo biochemical probes can demonstrate
      disease before anatomic abnormalities become evident. Gross changes in anatomy
      are no longer adequate endpoints for therapy protocols. Today, using physiologic
      imaging, we can evaluate the response to treatment within hours of administration
      of therapy. Adjuvant metabolic tumor imaging studies provide complimentary
      information to morphologic evaluation of human cancers that will ultimately lead
      to better patient care.

PMID- 1991269
TI  - Genotypic analyses of Richter's syndrome.
AB  - The authors report the immunogenotype of two cases of Richter's syndrome. The
      immunoglobulin gene rearrangement pattern obtained on Southern Blot analysis was
      found in both cases to be the same in leukemic blood cells and in the tissue
      involved by the lymphoma. The beta chain and gamma chain T-cell receptor gene
      rearrangement pattern exhibited a germ-line configuration in the peripheral blood
      cells and in the lymph node in Case 2, whereas in Case 1 the lymph node had a
      gene rearrangement in the beta chain, as well as in the gamma chain T-cell
      receptor, and the leukemic cells from bone marrow were found to be in a germ-line
      configuration for T-cell receptors (beta and gamma chains).

PMID- 1991271
TI  - Prostate cancer: transrectal ultrasound and pathology comparison. A preliminary
      study of outer gland (peripheral and central zones) and inner gland (transition
      zone) cancer.
AB  - A study was conducted to compare results of transrectal ultrasound with
      pathologic findings on 116 patients who underwent radical prostatectomy for
      treatment of prostate cancer. In 96% (111 of 116), transrectal ultrasound guided
      biopsies of a hypoechoic lesion proved cancer; seven patients had known Stage A
      cancer; one patient had cancer detected by palpation and not detected by
      ultrasound. Cancers in the outer gland (peripheral and central zones) were
      compared with cancers in the inner gland (transition zone) by both ultrasound and
      pathology. Forty-eight percent (52 of 108) of cancers originating in the outer
      gland showed extraprostatic extension (Stage C disease). The primary sites of
      tumor escape from the outer gland were the prostatic capsule (38%), anterior
      fibromuscular stroma (5%), seminal vesicle (18%), the base of the gland at the
      neurovascular bundle (21%), and the apex (31%). Twenty-two percent (17 of 54) of
      cancers originating in the inner gland (transition zone) showed extraprostatic
      extension (Stage C disease). The primary sites of tumor escape from the inner
      gland were the anterior fibromuscular stroma (6%) and apex (11%). Both histologic
      and biologic differences between outer and inner gland cancers were found when
      tumor size was controlled. Gleason scores were significantly different for inner
      and outer gland cancers, with mean scores of 6.2 +/- 1.6 and 7.4 +/- 0.9,
      respectively. An odds ratio of 8.6 confirmed the increased risk of extraprostatic
      extension for outer gland cancer. Outer gland cancers showed increased aggressive
      behavior of both histologic and biologic nature. The difference in biologic
      aggressiveness of outer and inner gland cancers has definite implications for
      treatment options. Use of other diagnostic parameters, such as DNA ploidy, may
      help to determine which cancers to treat and when to treat them; this may have
      more relevance for cancers originating in the inner gland. Strategic transrectal
      ultrasound guided biopsy affords accurate tumor mapping and staging when modes of
      internal spread and escape of cancer from both outer and inner gland are known.
      Thus, transrectal ultrasound may be our "window of observation" through which
      additional research may explain the histologic and biologic discrepancies between
      outer and inner gland cancers.

PMID- 1991272
TI  - The natural history of colorectal cancer. Opportunities for intervention.
AB  - There is now a better understanding of the natural history of colorectal cancer,
      which has provided a basis for intervention to influence outcome. The possible
      interventions include earlier detection of colorectal cancer, removal of
      premalignant adenomas, demonstration of the mucosal field defect that precedes
      neoplasia to evaluate baseline risk and its change with dietary modification, and
      identification of inherited and dietary risk factors. Five controlled trials
      evaluating early detection of colorectal cancer with fecal occult blood testing
      have enrolled more than 309,000 patients. Early stage cancers with improved
      survival has been observed, but data on mortality reduction have not as yet been
      reported. Studies of patients with adenomas have demonstrated high synchronous
      and metachronous rates as a basis for complete colon evaluation initially and a
      surveillance follow-up program. Hyperproliferation and lack of normal
      differentiation have been observed as a field defect in the colon preceding
      neoplasia. Inherited factors have recently been shown to be important in a larger
      proportion of individuals destined to develop colorectal adenomas and cancer.
      These observations of the natural history of colorectal cancer have provided new
      opportunities for the application of radiologic and endoscopic techniques in
      diagnosis and surveillance; each examination has its merit. Further research is
      needed to answer many critical questions that have been raised regarding the
      impact of these interventions.

PMID- 1991273
TI  - Imaging techniques in the diagnosis of carcinoma of the colon.
AB  - The variability in the published results for colonoscopy and barium enema
      examinations is confusing. With both, optimum results are dependent on meticulous
      preparation, technical excellence, and operator proficiency. It is a mistake to
      place colonoscopy and the barium enema in competitive positions; the two methods
      ideally complement one another in the evaluation of high risk individuals,
      including those with positive Hemoccult tests. The exclusion of significant
      pathology by the double-contrast enema can be relied on and is less costly to the
      patient. Detection of abnormalities by a barium enema should, when necessary, be
      followed by colonoscopic verification and/or biopsy. When used in this sequence,
      the procedures provide a cost-effective approach to the early detection and
      control of cancer; it is estimated that observance of the ACS guidelines can
      reduce mortality rates by 30%.

PMID- 1991274
TI  - Screening for lung cancer. A critique of the Mayo Lung Project.
AB  - The National Cancer Institute of the United States recently sponsored three large
      scale, randomized controlled trials of screening for early lung cancer. The
      trials were conducted at the Johns Hopkins Medical Institutions, the Memorial
      Sloan-Kettering Cancer Center, and the Mayo Clinic. Participants were middle-aged
      and older men who were chronic heavy cigarette smokers and thus at high risk of
      developing lung cancer. Screening procedures were chest radiography and sputum
      cytology, the only screening tests of established value for detecting early
      stage, asymptomatic lung cancer. In the Hopkins and Memorial trials the study
      population was offered yearly chest radiography plus sputum cytology every 4
      months. The control population was offered yearly chest radiography only. In
      these trials the addition of sputum cytology appeared to confer no lung cancer
      mortality rate advantage. The Mayo Clinic trial compared offering chest
      radiography and sputum cytology every 4 months to offering advice that the two
      tests be obtained once a year. This trial demonstrated significantly increased
      lung cancer detection, resectability, and survivorship in the group offered
      screening every 4 months compared with the control group. However, there was no
      significant difference in lung cancer mortality rate between the two groups. The
      statistical power of these trials was somewhat limited. Nevertheless, results do
      not justify recommending large-scale radiologic or cytologic screening for early
      lung cancer at this time.

PMID- 1991275
TI  - The applications of imaging in lung cancer.
AB  - The applications of imaging to the lung cancer patient have become more focused
      recently. Screening of high risk patients is not recommended even though
      intuition and clinical judgment prevail in practice to justify the use of chest
      radiographs in this patient category. Cross-sectional imaging procedures should
      be tailored to the staging process in the individual with a large central primary
      or to confirm an abnormality noted on the chest radiographs. The patient at high
      risk for thoracotomy is generally also subjected to radiologic staging. The
      radiologic staging process is reviewed and critiqued, emphasizing our role in
      identifying the disease sites that would suggest nonrespectability.

PMID- 1991276
TI  - Imaging bone tumors in the 1990s.
AB  - Progress in bone tumor management has occurred as a result of cooperation among
      surgeons, oncologists, pathologists, and radiologists. During the 1990s
      radiologists will contribute to care of patients with bone tumors in major ways.
      Tumor detection and preliminary diagnosis will be accomplished by radiography.
      Tumor local extent will be assessed by magnetic resonance imaging (MRI) and to a
      lesser degree by computed tomography (CT). Distant spread of malignancy will be
      documented by radionuclide scintigraphy (skeleton) and by CT (lungs). The
      combined estimate of local extent and distant spread will assure adequate staging
      before definitive management decisions. Preoperative closed percutaneous biopsy
      for histologic diagnosis will be accomplished on an outpatient basis under
      fluoroscopic or CT guidance. Arteriography will be employed for delivery of local
      chemotherapy. Some combination of arteriography, MRI, and MR spectroscopy will be
      used to evaluate tumor response. After limb-salvage surgery, MRI will
      sequentially assess the tumor bed; bone scintigraphy and CT will detect skeletal
      and pulmonary metastases. The radiologist's role will undergo continuous
      redefinition.

PMID- 1991277
TI  - Diagnostic imaging evaluation of Hodgkin's disease and non-Hodgkin's lymphoma.

PMID- 1991278
TI  - Primary neoplasms of the hollow organs of the gastrointestinal tract. Staging and
      follow-up.
AB  - The number of imaging modalities available to stage and follow-up patients with
      primary neoplasms of the gastrointestinal (GI) tract continues to increase.
      Magnetic resonance imaging (MRI), computed tomography (CT), and ultrasonography
      are useful techniques for both staging and follow-up. For staging, CT is most
      frequently used for the detection of liver metastases and is increasingly used as
      a substitute for the chest radiograph in the detection of lung metastases. CT is
      still the imaging test of choice for the preoperative staging of esophageal
      carcinoma. CT is less helpful in staging the patient with gastric carcinoma or
      colorectal carcinoma. The current usefulness of MRI in the staging of GI tract
      malignancies is limited by the lack of an adequate oral intraluminal contrast
      agent and degradation of images due to motion. Sonography, especially the new
      technique of endoscopic ultrasound, is promising for the detection of local
      invasion from GI tract malignancies. CT is used in the follow-up of patients with
      tumors of the GI tract to detect liver, adrenal, and nodal metastases as well as
      local recurrence because of the ability of CT to detect extraluminal masses. CT
      of the pelvis has been recommended as a routine follow-up procedure in patients
      who have undergone abdominal-peroneal resection. Both CT and MRI can be used to
      detect local recurrence, but suffer from the inability to differentiate scar from
      recurrent tumor. The initial hope that MRI would be capable of differentiating
      postoperative scar tissue from recurrent tumor has not been realized. Therefore,
      with positive CT or MRI findings, occasionally a percutaneous biopsy will be
      required to confirm local recurrence.

PMID- 1991279
TI  - Staging and follow-up of breast cancer patients.
AB  - Staging systems for breast cancer, unlike those of neoplasms in distant or
      recessed sites, allowed for the early development of clinical staging evaluation.
      It was established that clinical assessment of the breast lesion was often wrong
      compared with the pathologic examination (benign vs. malignant); clinical
      measurement of the tumor in centimeters was often larger than histologic size;
      and clinical assessment of axillary nodes (clear or metastatic) was incorrect in
      about 30% of cases. Although both clinical and pathologic staging provide
      effective discriminants for prognosis of treated patients, prognosis is more
      accurately determined by the pathologic stage. The single most important
      prognostic indicator is the axillary nodal status, and when positive, the number
      of positive nodes. The American Joint Committee on Cancer and the Union
      International Contra Cancer have agreed on a TNM staging for breast carcinoma,
      and this is the preferable staging system. Follow-up of treated patients is of
      most value in detecting local recurrence on the chest wall (after mastectomy) or
      in the irradiated breast (after lumpectomy), and also in early detection of
      contralateral breast cancer. Physical examination and periodic mammography are
      most useful. There is a tendency to overinvestigate asymptomatic patients (with
      bone scans, blood tests, etc.), but this has been correctly criticized in recent
      years.

PMID- 1991280
TI  - Oncologic imaging. Staging and follow-up of renal and adrenal carcinoma.
AB  - Computed tomography (CT) has emerged from the 1980s to play a dominant role in
      the pretreatment staging of renal and adrenal carcinomas. For detection,
      definition (staging), and determination of resectability or recurrence, CT with
      intravenous contrast enhancement, and more recently, magnetic resonance imaging
      (MRI) with gadolinium-DTPA, may be the only cross-sectional imaging studies
      required before institution of appropriate therapy. Carcinoma of the kidney is
      frequently diagnosed by serendipity or detected on incidental ultrasound or CT
      examinations. Real-time ultrasound and color flow Doppler offer unique
      information on tumor vascularity and major venous vascular involvement. Positive
      predictive values of 96% can be achieved for the diagnosis of renal cell
      carcinoma using contrast-enhanced CT scanning. For follow-up CT and MRI are the
      best imaging techniques for evaluation of the retroperitoneum. MRI may
      distinguish tumor recurrence from fibrosis in selected cases. Because primary
      neoplasms of the adrenal gland are rare and often exceed 10 cm at the time of
      initial diagnosis, the functional nature (endocrine) of adrenal carcinoma may be
      part of the clinical presentation. Because initial stage is critical to survival
      and extent of surgical therapy, a knowledge of tumor classification is essential
      to the optimal diagnostic evaluation. Newer imaging tests, CT and MRI, have
      superseded conventional urography, ultrasound, and radionuclide studies for the
      diagnosis and staging of adrenal cancer. Early diagnosis and low stage at
      presentation are critical to survival in patients with adrenal carcinoma. The
      current concepts for pretreatment imaging evaluation and the role of CT, MRI, and
      ultrasound are outlined. An oncologic imaging approach based on tumor staging and
      classification for patients with real or suspected renal cell carcinoma and
      adrenal carcinoma is essential to optimal patient care.

PMID- 1991281
TI  - Carcinoma of the female reproductive organs. Value of cross-sectional imaging.
AB  - Cross-sectional imaging techniques i.e., computed tomography (CT) and magnetic
      resonance imaging (MRI), play an integral role in the evaluation of patients with
      carcinoma of the female reproductive system. Neither CT nor MRI, however, are
      tissue-specific, and benign and malignant disease cannot be differentiated using
      these techniques alone. Therefore, the diagnosis is clinical and is based on
      history, physical examination, and histology. After the diagnosis has been made,
      CT and MRI are recommended for noninvasive evaluation of tumor extent, often
      helping in designing optimal therapy, thus facilitating more effective treatment
      and ultimately influencing patient prognosis. In evaluating tumors of the uterus,
      including endometrial and cervical carcinomas, CT is limited to the evaluation of
      more extensive disease. It is believed that the value of CT rises proportionately
      to the size and extent of disease. Its major limitation is suboptimal tissue
      contrast resolution, making differentiation between a small tumor and the
      surrounding normal tissue difficult. MRI renders excellent soft tissue contrast,
      allowing direct tumor visualization and assessment of tumor volume, depth of
      penetration, and extension to adjacent tissues. Assessment of these parameters is
      crucial in deciding on the choice of therapy, whether surgery, radiation,
      chemotherapy, or their combination. The initial management of ovarian cancer
      usually includes surgical staging with tumor debulking. CT remains the primary
      staging technique; its value resides primarily in identification of tumor
      metastases and in patient follow-up. Despite progress in the use of CT and MRI,
      second-look laparotomy for ovarian cancer has not been superseded. Technical
      advances in radiologic cross-sectional imaging have significantly improved the
      accuracy of noninvasive tumor staging. Although there are still limitations to
      these techniques, additional technical improvement and better tissue
      characterization are imminent.

PMID- 1991282
TI  - Retroperitoneal and pelvic lymph node imaging.

PMID- 1991283
TI  - Primary neoplasms of the central nervous system in children.
AB  - Modern diagnostic imaging techniques are able to detect primary neoplasms of the
      central nervous system (CNS) in children safely and accurately but with less
      specificity as to cell type or degree of malignancy. These neoplasms, often
      peculiar in cell type and size, mediated by hydrocephalus in their clinical
      presentation, demand careful and often extensive imaging techniques best to
      evaluate their geography and character. Added to these basic observations,
      determination of the neoplasm from surrounding edema, detection of possible
      spread, and evaluation of residual or recurrent neoplasm are prime
      responsibilities of the pediatric neuroradiologist toward the child,
      neurosurgeon, and oncologist.

PMID- 1991284
TI  - Magnetic resonance imaging in the evaluation of spinal tumors.
AB  - Magnetic resonance imaging (MRI), which has recently begun to replace
      myelography, postmyelography computed tomography (CT), and to some extent, bone
      scans, has become the procedure of choice in the evaluation of spinal tumors; the
      applications of MRI in this role are reviewed. In the extradural space, MRI is
      the most sensitive technique for the detection of tumors in the vertebral bodies.
      At the same time, it provides superb delineation of suspected thecal sac
      impingement. In the intradural extramedullary space, MRI is generally as accurate
      as myelography and postmyelography CT while being noninvasive. Finally, in the
      intramedullary space, MRI is unquestionably the procedure of choice in the
      evaluation of suspected cord tumors. In general, MRI has become the best initial
      procedure in the evaluation of suspected tumors of the spine, regardless of the
      space in which they may lie; frequently, it is the only required examination.

PMID- 1991285
TI  - Metastatic tumors of unknown origin.
AB  - The clinical appearance of metastatic lesions without an obvious primary source
      for the tumor is a common event. Tumor Registry figures and epidemiologic data
      grossly understate the actual frequency of unknown primaries, because primary
      sites are often "assigned" to patients on a best-guess basis without positive
      proof of a tumor's origin. In the majority of patients whose primary tumors have
      continued to elude detection, the extensive use of diagnostic imaging studies
      fails to produce information that alters the patients' clinical course. Rare
      exceptions will be cited, but these exceptions prove the general rule. Imaging
      studies should therefore be targeted for selected patients with disseminated
      malignancies in whom identification of their primary tumors could benefit quality
      of life or length of survival.

PMID- 1991286
TI  - Radioimmunology. Imaging and therapy.
AB  - Targeting of radioactivity to tumors using antitumor antibodies is evolving from
      a laboratory curiosity toward a practical diagnostic and therapeutic technique
      that promises widespread benefits for many common human cancers. The development
      of the hybridoma technique by Kohler and Milstein for producing monoclonal
      antibodies is probably the single most important contribution to the development
      of this field. A large array of monoclonal antibodies against many human tumors
      have been created and labeled with a variety of radioisotopes; 110 clinical
      trials have been identified from the literature between the interval of 1978 to
      the present. These studies are beginning to form the basis for certain
      conclusions regarding likely benefits for certain combinations of antitumor
      antibodies and isotopes in specific instances of clinical management in patients
      with malignant neoplasms. For example, in melanoma, lymphoma, neuroblastoma, and
      colorectal malignancies, radiolabeled antibodies have demonstrated occult tumors,
      which could not be disclosed with conventional methodologies. Radioimmunotherapy
      of malignant lymphoma is achieving durable remissions in patients who have failed
      conventional forms of therapy. For the most part, these advances have been
      achieved through intelligent application of known principles of immunochemistry,
      imaging physics, and tumor immunology. Progress has been slow but steady. In a
      few instances, the term "magic bullet" is warranted in describing the targeting
      of a particular radiolabeled antibody to a human tumor. I-131, 3-F8, an IgG3
      against the GD2 antigen of neuroblastoma, which was introduced by Cheung, and In
      111 T-101, against the CD5 antigen of T-cells, which was developed by Royston,
      stand out because of the consistency and high concentration of radioactive
      targeting to human tumors in clinical trials. If certain technical innovations
      fulfill their initial promise, the future will be bright for radioimmunologic
      methods of diagnosis and therapy. Genetic engineering will permit the development
      of "humanized" antibodies with biologic properties that favor tumor localization.
      New chemical approaches will broaden the range of isotopes available as
      diagnostic and therapeutic radiolabels. Application of modern imaging
      methodologies, such as positron emission tomography (PET), will detect more
      lesions of smaller size and permit quantitative imaging for dosimetry
      considerations. Greater speed and ease of use of computerized work stations will
      lead to the broader application of fusion imaging in which radioantibody images
      will be viewed simultaneously with TCT or MRI for better anatomic correlation of
      abnormal sites of antigen-reactive tumor deposits.

PMID- 1991287
TI  - Single photon emission computed tomography and positron emission tomography in
      cancer imaging.
AB  - Single photon emission computed tomography (SPECT) and positron emission
      tomography (PET) are now being used to improve the information available from
      radioisotopic imaging of patients with cancer. These nuclear medicine techniques
      offer the potential for studying regional function and biochemistry by using
      radiolabeled substrates. The chemical changes of malignancy precede anatomic
      changes, and PET and/or SPECT may detect these changes before anatomic changes
      have occurred. The superiority of SPECT compared with planar imaging has been
      demonstrated for cardiac and brain imaging. Radiopharmaceuticals containing
      technetium 99 m (99mTc) are best suited for SPECT imaging because large amounts
      of radioactivity are administered and the collimator-camera systems are optimized
      for the 140 keV photons of 99mTc. The current interest in imaging cancer with
      SPECT relates to the use of gallium 67 citrate and monoclonal antibodies labeled
      with iodine 123 or indium 111. SPECT can image these radioisotopes, but the
      advantages compared with planar imaging have not been clearly defined.
      Furthermore, the ability to quantitate the distribution of single photon emitters
      other than 99mTc has not been demonstrated. New SPECT systems with three heads or
      rings of detectors offer promise for improved, quantitative imaging. PET has the
      capability of imaging tracers with the biologically important elements C-11, N
      13, O-15, and F-18 used for positron labeling. These radioisotopes have short
      half-lives and require a cyclotron close to the PET facility. The most
      prominently used radiopharmaceutical for PET is F-18 fluorodeoxyglucose (FDG).
      PET studies with FDG in patients with primary brain tumors have demonstrated the
      ability to determine the degree of malignancy, to differentiate necrosis from
      recurrent tumor after radiation therapy or chemotherapy, and to predict
      prognosis. Other metabolic functions of cancer have been studied, including amino
      acid accumulation, thymidine uptake, oxygen utilization, intermediary metabolism,
      and receptor status. PET has the potential to make a major impact on the
      characterization of a malignancy and the effect of therapy.

PMID- 1991288
TI  - New directions in medical imaging of cancer. Magnetic resonance methods and
      single photon emission computed tomography.
AB  - Magnetic resonance methods and single photon emission computed tomography (SPECT)
      are developing technologies that provide both functional and anatomic
      information. Their role in the diagnosis and monitoring of cancer is the subject
      of current clinical research. Magnetic resonance imaging (MRI) delineates organs
      and tissue heterogeneities using differences in the relaxation parameters of
      water and fat protons; both protons and other nuclei can be imaged or studied by
      magnetic resonance spectroscopy (MRS) to provide information on the state of
      naturally occurring or infused molecules. SPECT quantifies the distribution of
      radiolabeled agents in tissues and organs; labeled monoclonal antibodies provide
      highly specific imaging of tumors. Spatial resolution is the limiting technologic
      factor. Proton MRI provides the highest current resolution, better than 1 mm in
      vivo in deep tissues, whereas the resolution of MRS and SPECT is limited to
      several cubic centimeters. Recent advances in these technologies have
      significantly increased their specificity and ability to detect small, deep
      lesions.

PMID- 1991289
TI  - Imaging of adult central nervous system primary malignant gliomas. Staging and
      follow-up.
AB  - A classification and staging system for primary adult gliomas was proposed. This
      system uses the high signal intensity found on proton density or T2-weighted
      magnetic resonance (MR) scans at the site of the tumor and surrounding edema
      (including infiltrating tumor).

PMID- 1991290
TI  - Proliferation and DNA ploidy in malignant breast tumors in relation to early oral
      contraceptive use and early abortions.
AB  - In 175 premenopausal breast cancer patients, a history of oral contraceptive (OC)
      use before 20 years of age was significantly associated with higher tumor cell
      proliferative activity, as indicated by a higher S-phase fraction (SPF), and a
      higher fraction of DNA aneuploid tumors, compared with later or never users (P =
      0.05 and p = 0.01, respectively). The higher SPF among early OC users was
      apparent in patients with aneuploid tumors but not in patients with euploid
      tumors. Abortions (spontaneous or induced) before the first full-term pregnancy
      also were associated with a higher SPF compared with other young patients with
      breast cancer (P = 0.03). Adjusting for parity and abortions or OC use,
      respectively, an early OC use was associated with a 43% higher SPF and early
      abortions were associated with 49% higher SPF. Younger patients had a higher SPF
      and a higher frequency of aneuploid tumors, but this was found to be because the
      users of OC had a lower median age at diagnosis. Among never users, no
      significant age relationship was seen for SPF or the frequency of aneuploidy. For
      the DNA analyses there is a selection of patients with breast cancer with larger
      tumors, and therefore the conclusions drawn in this article may not be
      generalizable to patients with smaller primary tumors, e.g., cases diagnosed at
      breast cancer screening. The higher tumor proliferative activity and frequency of
      aneuploidy in early OC users are in line with previously reported findings of
      worse prognostic indicators and a worse survival in early users of OC compared
      with other young women with breast cancer.

PMID- 1991291
TI  - Fludarabine therapy in hairy cell leukemia.
AB  - This study evaluated the efficacy of fludarabine, a new adenine nucleoside
      analogue, in typical and variant forms of hairy cell leukemia (HCL). Two patients
      with HCL and one patient with a variant form of HCL (HCL-variant) with resistant
      or progressive disease with prior treatments were studied. Fludarabine (30 mg/m2)
      was administered intravenously over 30 minutes daily for 5 days every month. Two
      patients (one with HCL and one with HCL-variant) achieved partial responses; the
      third patient had a minor response. This is the first report of encouraging
      activity of fludarabine in typical and variant forms of HCL. Further experience
      with fludarabine in these disorders is indicated.

PMID- 1991293
TI  - Radiation therapy in metastatic spinal cord compression. A prospective analysis
      of 105 consecutive patients.
AB  - One hundred thirty consecutive patients with metastatic spinal cord compression
      (MSCC) were entered in a therapeutic protocol in which radiation therapy (RT)
      played the main role. When MSCC is diagnosed by clinical-radiologic methods such
      as myelography with or without computed tomography (CT) or magnetic resonance
      imaging (MRI), steroids are given and RT treatment started within 24 hours. When
      diagnostic doubts exist or stabilization is necessary, surgery precedes RT.
      Chemohormonal potentially responsive tumors are also treated with chemotherapy or
      hormonal therapy. Twelve patients (9.2%) underwent surgery plus RT, and 118
      (90.8%) received RT alone. Thirteen (11%) early death patients were not
      evaluable. The 105 evaluable cases that received RT alone were analyzed. Median
      follow-up was 15 months (range, 4 to 38 months). Response among patients with
      back pain was 80%. In cases with motor dysfunction, 48.6% improved, and in 33 of
      105 patients (31.4%) without motor disability there was no deterioration. Forty
      percent of patients with autonomic dysfunction responded to RT. Median survival
      time was 7 months with a 36% probability of survival for 1 year. The median
      duration of improvement was 8 months. The most important prognostic factor was
      early diagnosis. Radiosensitivity of tumor was only important in paraparetic
      patients in predicting response to RT. Complete myelographic block significantly
      diminished response to RT. Vertebral collapse did not influence response or
      survival.

PMID- 1991292
TI  - Treatment of patients with advanced colorectal cancer with cisplatin, 5
      fluorouracil, and leucovorin.
AB  - Based on in vitro studies that have demonstrated synergy between 5-fluorouracil
      (5-FU), leucovorin (LV), and cisplatin (CDDP) against human colon cancer cell
      lines, a clinical trial was initiated to determine the effects of this
      combination in patients with advanced unresectable colorectal carcinoma. Fifty
      nine patients were enrolled in the study and 12 of them had received prior
      conventional 5-FU chemotherapy. Treatment consisted of 4 weekly courses of high
      dose LV (200 mg/m2) administered by intravenous (IV) bolus, followed by 5-FU (550
      mg/m2) and CDDP (20 mg/m2) each administered as a 2-hour infusion on 4
      consecutive days. After a median of 5.5 treatment cycles, objective tumor
      response was seen in 20 of 59 patients (34%) (this included 3 complete
      remissions). The response rate in the 47 previously untreated patients was 38%
      (95% confidence limits, 26% to 53%). Stable disease occurred in 16 (27%)
      patients, whereas the tumor progressed in 23 (39%) patients. The median survival
      time was 11.5 months, with 15% of the patients alive at 2 years. The regimen was
      well tolerated and the primary side effects were mild and reversible
      gastrointestinal symptoms and myelosuppression. There was no episode of life
      threatening toxicity. Eastern Cooperative Oncology Group (ECOG) Grade III adverse
      reactions that required 25% dose reductions occurred in only 14% of the patients.
      The results of this trial suggest that 5-FU, LV, and CDDP is an active, safe, and
      well-tolerated combination regimen in patients with advanced colorectal cancer.

PMID- 1991294
TI  - The prognostic value of image analysis in ovarian cancer.
AB  - Histologic grading is very important for treatment decisions in ovarian cancer.
      All grading systems contain a significant subjective component, which could be
      reduced by including objective measurements into the diagnostic decision. Image
      analysis was used to determine nuclear area and ploidy distributions in 42
      patients with epithelial ovarian cancer, and the results were related to tumor
      grade and clinical outcome. The mean nuclear area, mean optical density, number
      of hyperploid cells, and the standard deviation between measurements were
      significantly higher in Grade 2 and 3 tumors compared with Grade 1 tumors, in
      rapidly progressive tumors compared with less aggressive malignancies, and in
      recurrent tumors compared with primary lesions. The number of nuclei with very
      high DNA content was found to be of prognostic importance. Image analysis thus
      provides additional prognostic information in epithelial ovarian cancer.

PMID- 1991295
TI  - Structural and functional integrity of ovarian tumor tissue obtained by
      ultrasonic aspiration.
AB  - For patients with ovarian epithelial cancer, survival increases when residual
      disease approaches zero after surgical removal of the tumor. A previous study
      using the Cavitron Ultrasonic Surgical Aspirator (CUSA) (Cavitron Lasersonic
      Corp., Stamford, CT) showed the successful removal of ovarian tumors from areas
      often considered unresectable: the diaphragm, spleen, stomach, and small bowel.
      However, the CUSA has not yet been approved by the Food and Drug Administration
      for gynecologic surgery except on an experimental basis. This study was designed
      to test whether ultrasonic irradiation produced by the CUSA caused alterations in
      cell structure or physiology of gynecologic tissue in adjacent areas. Paired
      tumor samples, unirradiated and irradiated, were obtained from ten patients, and
      portions were sent for pathologic structural evaluation and physiologic tissue
      culture evaluation. Histologic sections, stained with hematoxylin and eosin,
      showed that CUSA irradiation produced only minor tissue distortion as observed
      under the light microscope. A correct diagnosis would have been made in all cases
      had only tissue fragments obtained from the CUSA specimen trap been stained. For
      nine of ten patients, initial tumor cell viability was similar in the two
      specimen types. Flow cytometric DNA analysis confirmed that surgical methods
      produced matched samples. Cells that survived high-frequency ultrasound appeared
      functionally intact. For five of eight patients, the cells from the CUSA specimen
      traps survived and/or divided to a greater extent than those from the knife
      dissected tumors. Cells from both surgical routes attained a similar number of
      passages in culture. It seems reasonable to extrapolate these in vitro
      observations with pelvic tumor tissues to normal surrounding tissue left in situ.
      Thus pelvic tissue is believed to be uninjured by CUSA ultrasonic irradiation.

PMID- 1991296
TI  - Induction of cytotoxicity of the renal hilar lymph nodes by pedal subcutaneous
      administration of interleukin-2 in patients with renal cancer.
AB  - The authors attempted to increase the cytotoxicity of the renal hilar lymph nodes
      in ten patients with renal cell carcinoma by administration of recombinant
      interleukin-2 (IL-2) into the subcutaneous tissue of the instep. A total of 5000
      to 21,000 units was given over 3 to 12 preoperative days. Mononuclear cells
      separated from the lymph nodes excised from the renal hilum at surgery served as
      the effector cells. Fresh autologous tumor cells and three cultured cell lines,
      K562, Raji, and ACHN, served as the target cells. Cytotoxicity was measured by a
      chromium-releasing assay. The results showed that the mononuclear cells from the
      lymph nodes of the patients given IL-2 became cytotoxic to all target cells.
      Surface markers of lymphocytes in the lymph nodes were unchanged. Peripheral
      blood lymphocytes showed increased cytotoxicity only against Raji cells. Adverse
      effects were mild or moderate and included local redness, high fever, liver
      dysfunction, and toxic erythema.

PMID- 1991297
TI  - Receptors for epidermal growth factor and steroid hormones in primary laryngeal
      tumors.
AB  - The authors investigated the presence of epidermal growth factor (EGF-R),
      estrogen (ER), progesterone (PR), and androgen (AR) receptors in 42 laryngeal
      squamous cell carcinomas and 20 normal laryngeal mucosa specimens. EGF-R were
      expressed in all tumor specimens analyzed, with significantly higher levels in
      tumor samples compared with normal mucosa (P less than 0.05). The
      immunohistochemical study demonstrated the presence of EGF-R in basal and
      parabasal cells of normal mucosa and in most of the cancer cells. There was no
      correlation between EGF-R and tumor localization or T classification. On the
      other hand, the authors did find an interesting correlation between EGF-R levels
      and grading, EGF-R levels being significantly higher in G3 than in G1-G2 tumors.
      Moreover, the three patients whose tumors expressed the highest EGF-R levels had
      disease recur within 8 months. Among tumor specimens, 9.5%, 35.7%, and 9.5%
      expressed very low but detectable ER, PR, and AR levels, respectively. No
      statistically significant difference was found between the levels of steroid
      receptors in the tumor and normal mucosa specimens, and neither was there any
      correlation of ER, PR, and AR with the pathologic findings. The authors' results
      suggest that the EGF-R system may play a role in regulating the growth of
      laryngeal cancer. Additional studies should demonstrate whether, as in other
      tumor types, EGF-R expression may have prognostic significance in human laryngeal
      cancer.

PMID- 1991298
TI  - The expression of progesterone receptors coincides with an arrest of DNA
      synthesis in human breast cancer.
AB  - Two main models to account for the heterogeneous expression of estrogen receptors
      (ER) and progesterone receptors (PR) in human breast cancer have been proposed:
      the clonal model and the stem cell model. The authors previously provided
      evidence supporting the stem cell model since it was found that most of the
      proliferating cells in ER-positive (ER+) human breast cancer lack ER and that the
      ER-negative (ER-) and ER+ subpopulations are interrelated. The authors have
      analyzed in eighteen ER+/PR+ primary breast tumors the simultaneous expression of
      ER or PR (by immunohistochemistry) and DNA synthesis (by autoradiography) after
      30 minutes of 3H-thymidine incorporation. The authors demonstrated that: (1) the
      average numbers of ER+ and PR+ cells were similar (36.8 +/- 10.7% and 39.3 +/-
      17.6%, respectively); (2) The thymidine-labeling indexes of the ER+, ER-, PR+,
      and PR- subpopulations were 0.53 +/- 0.69%, 0.74 +/- 0.49%, 0.21 +/- 0.21 and
      0.94 +/- 0.54%, respectively; and (3) 75.2% of the DNA-synthesizing cells were ER
      , and 88.8% of them were PR-. The authors conclude that the cellular
      subpopulations expressing ER and PR were not identical, and the expression of PR
      was associated with a lower rate of cellular proliferation than was ER
      expression.

PMID- 1991299
TI  - Lymphomas of the breast. A clinicopathologic and immunohistochemical study of
      primary and secondary cases.
AB  - Primary mammary lymphoma is rare, and little is known about the immunophenotype
      of such cases. The authors studied both primary and secondary breast lymphomas
      with a broad panel of T- and B-cell markers using paraffin-embedded tissue and
      the avidin-biotin immunoperoxidase method. Cases of primary B-cell lymphoma were
      further tested to determine light and heavy chain type. Thirty-five cases were
      analyzed, including 16 primary lymphomas. Diffuse large cell lymphoma was present
      in ten of 16 primary and 14 of 18 secondary cases. Lymphoepithelial lesions in
      ducts and lobules and frequent vascular involvement were found in both primary
      and secondary cases. Immunohistochemistry studies on 13 tumors revealed all of
      the primary tumors to be B-cell in origin, except for one case of primary T-cell
      lymphoma; to the authors' knowledge, this represents the first description of
      this entity. Fifteen of 17 secondary tumors exhibited B-cell markers and one of
      17 exhibited T-cell markers; in only one case could lineage not be determined.
      Among primary B-cell cases, IgM was found to be the most frequent heavy chain
      type; IgA reactivity was found in only one case. Survival was related to stage
      and histologic characteristics; patients with Stage II disease and higher grade
      histologic lesions had a worse prognosis. Half of the patients with primary
      lymphoma have had recurrent disease. Although local recurrences were observed,
      the authors also saw a tendency for recurrence in other extranodal sites. The
      authors conclude that, although primary lymphoma of the breast is compatible with
      long-term survival, a significant number of patients eventually die of their
      disease. As with other extranodal lymphomas, survival rate appears most related
      to stage of disease. Also, the vast majority of primary tumors are B-cell in
      origin, express IgM heavy chain, and can be considered tumors of mucosa
      associated lymphoid tissue.

PMID- 1991300
TI  - Prognostic implications of DNA histogram, DNA content, and histologic changes of
      regional lymph nodes in patients with lung cancer.
AB  - Forty-six cases of resected lung cancer, including 20 cases at Stages I and II
      and 26 cases at Stage III (N2), were subdivided into two groups: a good prognosis
      group with a longer survival period and a poor prognosis group in which the
      patients died earlier of the cancer. From paraffin-embedded lymph node tissues of
      these patients, the authors examined DNA histogram pattern and DNA content, using
      flow cytometry, and histologic hyperplasia of germinal center and paracortical
      area; they also evaluated their correlation with the prognosis. In the good
      prognosis group at Stages I and II, paracortical hyperplasia (PH) of the lymph
      nodes was observed significantly more frequently. In the good prognosis group at
      Stage III, the incidence of PH, G2M phase in the DNA histograms, and DNA content
      were all significantly higher. DNA content was positively correlated with the
      grade of PH.

PMID- 1991301
TI  - Association of expression between N-myc gene and major histocompatibility complex
      class I gene in surgically resected human neuroblastoma.
AB  - Amplification of the N-myc gene in neuroblastoma correlates with advanced stage
      and poor prognosis. Association of the expression between N-myc and major
      histocompatibility complex (MHC) class I genes in 33 neuroblastomas obtained from
      Japanese children was investigated. Amplification of the N-myc gene was observed
      in two of five cases in Stage III, six of 11 cases in Stage IV, and one of five
      cases in Stage IV-S. In each case, the expression of N-myc gene was significantly
      increased. The expression was also increased in cases without amplification of
      the N-myc gene, the origin being from the suprarenal region. Expression of the
      MHC class I gene was significantly decreased in five of these nine with a high
      level of N-myc expression with amplification. These results suggest that the down
      modulation of the MHC class I expression may be associated with the high level of
      expression and amplification of N-myc gene in the advanced stage of
      neuroblastoma.

PMID- 1991302
TI  - Clinical significance of hematologic parameters in non-Hodgkin's lymphoma at
      diagnosis.
AB  - Three hundred seventeen patients with non-Hodgkin's lymphoma (NHL) (54 low grade,
      180 intermediate grade, 76 high grade, and seven unclassified) treated with
      chemotherapy were evaluated for the presence of hematologic abnormalities at
      diagnostic staging. Anemia was present in 42%, leukopenia in 6%, thrombocytopenia
      in 13%, leukocytosis in 26%, and thrombocytosis in 14% at presentation. The
      presence of bone marrow involvement by lymphoma was more likely to be associated
      with leukopenia and thrombocytopenia than the absence of bone marrow involvement.
      Although anemia was slightly more common in patients with bone marrow lymphoma
      than in those without marrow lymphoma, the difference was not statistically
      significant. Hematologic parameters were similar for patients with B-cell or T
      cell lymphoma. Evidence of bone marrow failure with multiple cytopenias was
      present in 26 patients (8%). Leukoerythroblastosis was present in 2%. Circulating
      lymphoma was present in 9.5%. Anemic patients had a shorter survival time than
      nonanemic patients, whether bone marrow was involved by lymphoma or not. Survival
      was not affected by the presence of leukopenia or mild leukocytosis, but, in
      patients without marrow lymphoma, leukocytosis with a leukocyte count greater
      than 20 x 10(9)/l was associated with short survival length. Thrombocytopenia was
      associated with short survival time only in patients with bone marrow involvement
      by lymphoma. Patients with multiple cytopenias or leukoerythroblastosis had short
      survival times, but the presence of circulating lymphoma did not alter survival
      when compared with other patients with bone marrow involvement by lymphoma. These
      data suggest that hematologic evaluation at the time of diagnostic staging of NHL
      provides useful prognostic information that may have therapeutic implications.

PMID- 1991303
TI  - Amplification of oncogenes in mammary carcinoma shown by fine-needle biopsy.
AB  - A procedure that measures the amplification of oncogenes in human cancer cells is
      described. The cells were obtained by fine-needle biopsy to allow repeated
      sampling from individual metastases. A drawback was the low number of cells
      obtained, but this could be overcome by using a slot-blot hybridization technique
      to measure gene amplification. Two patients with mammary cancer (primary tumors
      or metastases), analyzed for the levels of amplification of the oncogene erb-B2,
      are described in detail. This technique is suitable for analyzing alterations
      occurring during cancer progression and for identifying subgroups of mammary
      cancer with different characteristics.

PMID- 1991304
TI  - Predicting recurrence time of esophageal carcinoma through assessment of
      histologic factors and DNA ploidy.
AB  - Cytophotometric analysis of nuclear DNA content was done in 128 patients with
      squamous cell carcinoma of the esophagus. The relationship among histopathologic
      features, DNA distribution pattern, and survival time was investigated from the
      standpoint of recurrence. Of 128 patients, 77 (60.1%) died of recurrence within 2
      years after surgery: 16 (12.5%) from 2 to 5 years and two (1.6%) over 5 years.
      The rate of death of recurrence within 2 years was higher in patients with T4 or
      N1 than T1, T2, and T3 or N0 (P less than 0.01). Survivors over 5 years more
      frequently possessed type II DNA pattern than types III and IV (P less than
      0.05). The rate of death of recurrence within 2 years was 34.4% in type II, which
      was lower than the 59.6% rate in type III (P less than 0.05) and the 76.6% rate
      in type IV (P less than 0.01). Survivors from 2 to 5 years were higher in type
      III than in type IV (P less than 0.05), and recurrence over 5 years was found
      only in type II. This inclination was more apparent in those with curative
      resection. In the patients with type II, careful follow-up may be needed over 5
      years for late recurrence. However, in those with type IV, no recurrence over 2
      years could be regarded as healed because most of their recurrences occur within
      2 years. These findings suggest that the growth rate of esophageal carcinoma
      should reflect DNA aneuploidy, and the DNA analysis of esophageal carcinoma
      should be a valuable parameter for postoperative follow-up planning.

PMID- 1991305
TI  - Primary and metastatic pulmonary meningioma.
AB  - Patient 1 was a 53-year-old man who had a very rare primary pulmonary meningioma
      that developed in the left lingular segment. When this report was written, 7
      years had passed since he underwent operation, and no recurrence of the
      meningioma had been detected. In Patient 2, a 61-year-old woman, multiple
      pulmonary metastases were confirmed 19 years after she had undergone operation
      for multiple cerebellar meningiomas, and the metastases were resected. After 2
      years, multiple intraperitoneal metastases were found, and thus aggressive
      surgery was performed. Currently, 22 years after the operation for the primary
      cerebellar meningioma, the patient is alive without any subjective symptoms,
      although intraperitoneal metastases have recurred. To date, only four cases (all
      in women) of primary pulmonary meningioma have been reported. Case 1 reported in
      this article is thus the first case in a male patient to be reported, and, in
      addition, this patient also has the first reported case to have been evaluated
      for more than 5 years. In Case 2, however, each of the excised extracranial tumor
      lesions was histologically homogeneous and showed a hemangiopericytomatous
      pattern. The histologic picture of those tumor lesions was exactly the same as
      the picture of a small portion of the cerebellar meningiomas excised 19 years
      earlier. Thus, all those extracranial tumor lesions were diagnosed to be
      metastatic meningiomas. However, it is difficult to explain why there had been no
      symptoms for as long as 19 years until the pulmonary metastases were discovered.

PMID- 1991306
TI  - Transurethral-resection zone prostate cancer detected at cystoprostatectomy. A
      detailed histologic analysis and clinical implications.
AB  - The authors identified incidental adenocarcinoma of the prostate in serial cross
      sections of prostates from 61 of 100 patients having cystoprostatectomy for
      bladder cancer. In 20 patients, cancer foci were in the prostatic region
      accessible to transurethral resection (TUR). Eight of these 20 patients had stage
      A1 disease (less than or equal to 3 foci); in six of these patients all foci were
      located at or within the transition-zone boundary only. Twelve patients had stage
      A2 disease (greater than 3 foci); in none were more than three foci at or within
      the transition-zone boundary. Among the 20 patients, 84 tumor foci were
      distributed as follows: 62% in the peripheral zone, 10% in the transition zone,
      3% in the central zone, and 25% in the transition zone boundary. The authors'
      data suggest that Stage A prostate cancer, like larger clinically detectable
      cancers, is multifocal, multizonal, and similarly distributed with respect to the
      urethra. No case of Stage A1 disease would have been reclassified as Stage A2 by
      repeat TUR of the entire transition zone and transition zone boundary. The
      authors' results confirm those of previous studies that report a high incidence
      of residual carcinoma in regions not accessible to TUR in patients with
      presumptive Stage A1 disease and suggest that ultrasonography and
      ultrasonographically guided biopsies, rather than repeat TUR, may more accurately
      define the extent of Stage A disease in some patients.

PMID- 1991307
TI  - Serial immunocytologic analysis of blood for tumor cells in two patients with
      neuroblastoma.
AB  - Tumor surveillance tests are used to determine whether malignant cells are
      responsive or resistant to therapeutic regimens. For patients with neuroblastoma,
      conventional methods of surveillance are not sensitive enough. Because tumor
      cells are shed into the circulation, immunocytologic analysis of blood may
      function as a sensitive monitoring system. In this study, five blood samples were
      obtained from two patients with disseminated neuroblastoma at diagnosis and
      during therapy. These samples were analyzed with monoclonal antibodies and
      immunoperoxidase staining to determine whether circulating neuroblasts were
      present. In both patients, the presence or absence of circulating neuroblasts
      yielded information that was more sensitive than that from conventional tests.
      The authors conclude that immunocytologic analysis of blood should be included
      with conventional monitoring methods for surveillance of patients with
      disseminated neuroblastoma.

PMID- 1991308
TI  - Hodgkin's disease in children 4 years of age or younger.
AB  - The natural history of Hodgkin's disease in children younger than 4 years of age
      is unknown. Thirty-eight patients younger than 4 years of age at the time of
      diagnosis of Hodgkin's disease were treated at the member institutions of the
      Pediatric Oncology Group. They were found to be predominantly white and male with
      early-stage disease. Mixed cellularity and nodular sclerosing histologies were
      most commonly seen and occurred in equal frequency. They responded to therapy
      extremely well attaining a complete remission rate of 92% to 94%. Even after
      relapse, they can be successfully retrieved with salvaging therapy.

PMID- 1991309
TI  - Primary central nervous system lymphoma as a secondary malignancy.
AB  - Primary central nervous system lymphoma (PCNSL) is a rare neoplasm, but it is
      occurring with increased frequency even among apparently immunocompetent
      patients. Although secondary malignancies frequently involve the lymphoreticular
      system, PCNSL has been reported as a second neoplasm only once previously. Seven
      patients are discussed who developed PCNSL after successful treatment for a prior
      neoplasm. The original cancer was colon (one), breast (one), thyroid (one),
      Hodgkin's disease (two), and non-Hodgkin's lymphoma (two). Patients with systemic
      non-Hodgkin's lymphoma were thought to have a separate cerebral lymphoma on the
      basis of a prolonged disease-free interval from their systemic lymphoma, and the
      absence of systemic disease, when PCNSL was diagnosed and through subsequent
      follow-up. The PCNSL developed a median of 10 years after the diagnosis of the
      first tumor and 6 years after the last evidence of systemic disease. The
      diagnosis of PCNSL was often delayed because of confusion with brain metastases,
      and initial shrinkage or disappearance of the lesion after corticosteroids.
      Formation of PCNSL may be a consequence of treatment for the first malignancy,
      reflect an unidentified inherent predisposition to neoplastic transformation, or
      result from the changing epidemiology of PCNSL in the general population. These
      mechanisms are not mutually exclusive, and a single hypothesis cannot account for
      all these cases.

PMID- 1991310
TI  - Lung cancer in patients younger than 40 years of age.
AB  - The records of 52 patients younger than 40 years of age who had bronchogenic
      carcinoma diagnosed between 1965 and 1985 were reviewed. The preponderance of
      adenocarcinoma (54%), the lower male-female ratio in this age group compared with
      patients age 40 or older (2:1), the importance of cigarette smoking as a
      causative factor (80% of patients), the long mean duration of symptoms (5
      months), and the high incidence of advanced stage at diagnosis (77% Stages III
      and IV) in these patients are findings similar to those reported in other
      published series. There was no significant difference in resectability (23%
      versus 19%), median survival length (5.3 months versus 6.9 months), median
      survival length of patients who had surgical resection (10.5 months versus 10.8
      months), and 5-year survival rate (11.5% versus 6.3%) in these patients compared
      with a randomly selected group of 260 patients with lung cancer who were age 40
      or older.

PMID- 1991311
TI  - A recurrent pelvic desmoid tumor successfully treated with tamoxifen.
AB  - A case of recurrent retroperitoneal desmoid tumor successfully treated with
      tamoxifen (Nolvadex tablets, ICI Pharma, Division of ICI Americas, Wilmington,
      DE) is reported. The patient presented late in her second pregnancy with a large
      retroperitoneal pelvic desmoid tumor that was treated with surgical excision and
      megestrol acetate. When the tumor recurred 12 months later, it was again treated
      with surgery, this time followed by radiation therapy. The desmoid tumor quickly
      recurred. The patient was then treated with tamoxifen, resulting in a complete
      tumor regression that has remained stable for 27 months. Tamoxifen should be
      considered as first-line therapy in recurrent desmoid tumors.

PMID- 1991312
TI  - Serous papillary adenocarcinoma of the tunica vaginalis of the testis with
      metastasis.
AB  - Testicular or paratesticular neoplasms that resemble the common epithelial type
      of ovarian tumor are quite rare. The authors report the case of a 29-year-old man
      with a metastatic serous papillary adenocarcinoma arising from the tunica
      vaginalis. To the authors' knowledge, this is the first reported case of a serous
      carcinoma of the tunica vaginalis behaving in a malignant fashion. The fact that
      clinically apparent metastatic disease occurred 4 years after initial
      presentation suggests that development of metastases is a late event.
      Unfortunately, the tumor has been refractory to therapy with chemotherapeutic
      agents with activity against ovarian malignancies.

PMID- 1991313
TI  - Rural-urban differences in stage at diagnosis. Possible relationship to cancer
      screening.
AB  - Stage at diagnosis was examined for various malignancies identifiable through
      screening to determine whether rural-urban differences exist in Georgia. Data
      were obtained from a population-based cancer registry which registers all
      incident cancers among residents of metropolitan Atlanta and ten neighboring
      rural counties. Black and white patients with a first primary invasive malignancy
      newly diagnosed between 1978 and 1985 were included in this study. Residents of
      the rural area were twice as likely to have unstaged cancers (18.3%) as were
      urban residents (9.6%). Among patients with known stage at diagnosis, rural
      patients tended to have more advanced disease than urban patients. The relative
      excess of nonlocalized malignancies in rural Georgia was 21% for whites and 37%
      for blacks. The rural excess of nonlocalized prostate cancer among blacks was
      especially pronounced. Differences in access to or utilization of early detection
      methods may contribute to the rural-urban differential in the extent of disease
      at diagnosis.

PMID- 1991314
TI  - Hereditary ovarian cancer. Heterogeneity in age at diagnosis.
AB  - An unknown fraction of the ovarian cancer burden occurs in women with a family
      history indicative of a putative autosomal dominantly inherited cancer
      susceptibility syndrome. The results from a five-generation, extended, hereditary
      breast-ovarian cancer kindred are described 10 years after it was initially
      ascertained. Significantly more cancers were observed in high-risk family members
      during this decade than were expected (P less than 0.001). The age of ovarian
      cancer diagnosis was studied in additional ovarian cancer-prone families of three
      types: site-specific ovarian cancer syndrome, the breast-ovarian cancer syndrome,
      and Lynch syndrome II. The age of onset in each of the three sets was
      significantly (P less than 0.001) earlier than the general population mean of 59,
      and there were significant differences in the age of onset (P = 0.050) among
      these three cohorts. Ovarian cancer histology was similar to that of patients
      with negative family histories. There may be clinically significant heterogeneity
      in the age at diagnosis of ovarian cancer among these ovarian cancer-prone
      syndromes. This has important implications for understanding its natural history
      and targeting surveillance-management strategies.

PMID- 1991315
TI  - Cancer in relatives of survivors of childhood sarcoma.
AB  - Relatives of 88 long-term survivors of childhood sarcoma were examined for the
      familial cancer syndrome of sarcoma, breast cancer, and other neoplasms (Li
      Fraumeni syndrome). Twenty-six of 402 close relatives developed cancer (expected,
      23.8), including breast cancer in four mothers (expected, 3.1). Two sarcoma
      probands who developed second malignant tumors have multiple relatives with
      cancer and might have an inherited predisposition. An increased cancer risk and
      exceptional requirement for disease screening appear to be confined to first
      degree relatives of a small fraction of children with sarcoma, notably probands
      with second cancers.

PMID- 1991316
TI  - Motorizing the spinal cord.

PMID- 1991317
TI  - Regulation of transcription and cell identity by POU domain proteins.

PMID- 1991318
TI  - A novel cysteine-rich sequence motif.

PMID- 1991319
TI  - How proteins enter the nucleus.
AB  - Nuclear protein import is a selective process. Proteins destined for the nucleus
      contain NLSs. These short stretches of amino acids interact with proteins located
      in the cytoplasm, on the nuclear envelope, and/or at the nuclear pore complex.
      Following binding at the pore complex, proteins are translocated through the pore
      into the nucleus in a manner requiring ATP. The biochemical dissection of the
      nuclear pore complex has begun. Alteration of protein import into the nucleus is
      emerging as a new and complex form of regulation. However, we are left with the
      following problems: How do proteins move through the cytoplasm to reach the
      nuclear pore? How does the nuclear pore complex open and close in a selective
      manner? How is ATP utilized during import? And finally, how is bi-directional
      traffic of both proteins and RNA through the pore regulated?

PMID- 1991320
TI  - Activation domains of stably bound GAL4 derivatives alleviate repression of
      promoters by nucleosomes.
AB  - GAL4 derivatives containing an activation domain alleviated repression of a
      promoter during nucleosome assembly. A GAL4 derivative lacking an activation
      domain stably bound the promoter during nucleosome assembly but was not
      sufficient to preserve promoter function. The activation domain of GAL4
      derivatives was essential for preserving promoter function, and thus the
      transcriptional stimulatory activity attributable to these activation domains
      increased dramatically during nucleosome assembly. Furthermore, promoter-bound
      activation domains allowed the formation of preinitiation complexes after
      nucleosome assembly. Finally, GAL4 derivatives containing activation domains
      significantly stimulated transcription through bacterially produced yeast TFIID
      only from nucleosome-assembled templates. These data indicate that acidic
      activation domains stimulate transcription by enhancing the ability of basal
      transcription factors to compete with nucleosomes for occupancy of the promoter.

PMID- 1991321
TI  - Stable length polymorphism of up to 260 kb at the tip of the short arm of human
      chromosome 16.
AB  - We have completed a long-range restriction map of the terminal region of the
      short arm of human chromosome 16 (16p13.3) by physically linking a distal genetic
      locus (alpha-globin) with two recently isolated probes to telomere-associated
      repeats (TelBam3.4 and TelBam-11). Comparison of 47 chromosomes has revealed
      major polymorphic length variation in this region: we have identified three
      alleles in which the alpha-globin genes lie 170 kb, 350 kb, or 430 kb from the
      telemere. The two most common alleles contain different terminal segments,
      starting 145 kb distal to the alpha-globin genes. Beyond this boundary these
      alleles are nonhomologous, yet each contains sequences related to other
      (different) chromosome termini. This chromosome size polymorphism has probably
      arisen by occasional exchanges between the subtelomeric regions of nonhomologous
      chromosomes; analogous length variation is likely to be present at other human
      telomeres.

PMID- 1991322
TI  - Scrambled exons.
AB  - Using a sensitive assay for RNA expression, we identified several abnormally
      spliced transcripts in which exons from a candidate tumor suppressor gene (DCC)
      were scrambled during the splicing process in vivo. Cloning and sequencing of PCR
      amplified segments of the abnormally spliced transcripts showed that exons were
      joined accurately at consensus splice sites, but in an order different from that
      present in the primary transcript. Four scrambled transcripts were identified,
      each involving a different pair of exons. The scrambled transcripts were found at
      relatively low levels in a variety of normal and neoplastic cells of rodent and
      human origin, primarily in the nonpolyadenylated component of cytoplasmic RNA.
      These results demonstrate that the splicing process does not always pair
      sequential exons in the order predicted from their positions in genomic DNA, thus
      creating a novel type of RNA product.

PMID- 1991323
TI  - Two interdependent basic domains in nucleoplasmin nuclear targeting sequence:
      identification of a class of bipartite nuclear targeting sequence.
AB  - Point mutagenesis of the nuclear targeting sequence of nucleoplasmin has
      identified two interdependent basic domains. These are separated by 10
      intervening "spacer" amino acids that tolerate point mutations and some
      insertions. Amino acids in both basic domains are required for nuclear targeting,
      and the transport defect of a mutation in one domain is amplified by a
      simultaneous mutation in the other. Therefore, these basic domains are
      interdependent. A strikingly similar motif of two clusters of basic residues is
      seen in the nuclear targeting sequence of Xenopus N1. It is also conserved in the
      related nucleolar protein NO38. Several other short sequences known to be
      necessary for nuclear targeting fall within a similar motif.

PMID- 1991324
TI  - Control of cell pattern in the developing nervous system: polarizing activity of
      the floor plate and notochord.
AB  - Individual classes of neural cells differentiate at distinct locations in the
      developing vertebrate nervous system. We provide evidence that the pattern of
      cell differentiation along the dorsoventral axis of the chick neural tube is
      regulated by signals derived from two ventral midline cell groups, the notochord
      and floor plate. Grafting an additional notochord or floor plate to ectopic
      positions, or deleting both cell groups, resulted in changes in the fate and
      position of neural cell types, defined by expression of specific antigens. These
      results suggest that the differentiation of neural cells is controlled, in part,
      by their position with respect to the notochord and floor plate.

PMID- 1991326
TI  - Quantitative clonal analysis of the B cell repertoire in human lupus.
AB  - To gain further insight into the origin of autoantibody hyperproduction in human
      lupus, we quantitated the B cell repertoire toward exogenous and self-antigens.
      Using the Spot-ELISA method and two panels of nine exogenous and 10 self
      antigens, we found that the normal human immune repertoire comprises a high
      frequency of B cell precursors secreting IgM antibodies to self- and exogenous
      determinants. This repertoire was markedly deficient in precursors producing IgG
      able to bind self-antigens. In lupus patients, the absolute numbers of clone
      precursors of the immune repertoire expressing IgM receptors whose paratopes
      impart affinity to self- and exogenous determinants were higher than in control
      individuals. Additionally, IgG antibody-forming cell precursors with binding
      specificity for lupus-associated antigens were detectable in the repertoire of
      these patients. Based on these results, we propose that hyperproduction of human
      lupus-associated autoantibodies arises in a two-stage mechanism whereby a general
      activation of the multireactive immune B cell repertoire precedes an
      oligospecific expansion of selected B cell clonotypes.

PMID- 1991325
TI  - Demonstration of YAC target cell lysis by murine granulated metrial gland cells.
AB  - Granulated metrial gland (GMG) cells are a consistently observed but poorly
      understood feature of the murine uterus during successful pregnancy. From
      morphological studies and antibody phenotyping it has been suggested that GMG
      cells may be members of the natural killer (NK) cell lineage. However, lysis of
      murine NK cell targets by GMG cells has not been observed although lysis of
      freshly dissociated trophoblast cells by GMG cells has been recorded using
      timelapse video. We failed to demonstrate significant interactions between
      migrating GMG cells, collected from explant cultures under previously reported
      cultures conditions, and YAC target cells. However, YAC cell lysis did occur if
      hrIL-2 was present throughout the periods of explant culture and lysis assay.
      Furthermore, lysis was enhanced if the pregnant females were treated with the
      interferon inducer poly I.C. 24 hr before metrial gland collection. GMG cells
      expressed perforin and serine protease mRNA. Consistent with the lysis
      experiments, expression of these genes was enhanced when the cells were incubated
      with hrIL-2. Our data provide further support for a relationship between GMG
      cells and NK cells, but do not establish a relationship of identity since hrIL-2,
      a growth factor sufficient for the culture of NK cells, cannot support growth or
      prolong survival of GMG cells.

PMID- 1991328
TI  - Differential inhibition of mitogenic responsiveness by monoclonal antibodies to
      beta 2-microglobulin.
AB  - A panel of 10 monoclonal antibodies (MoAbs) to human beta 2-microglobulin (beta
      2m) was used to evaluate the modulation of lymphocyte activation induced by
      different mitogenic stimuli. All 10 MoAbs inhibited proliferative responses of
      peripheral blood mononuclear cells (PBMC) to phytohemagglutinin (PHA),
      concanavalin A (Con A), pokeweed mitogen (PWM), and allogeneic cells in mixed
      lymphocyte culture (MLC), although some MoAbs were inhibitory at much lower
      concentrations than others. No enhancement or direct mitogenicity was observed,
      but at low MoAb concentrations a delayed peak response sometimes occurred.
      Differentiation of B cells in PWM-stimulated PBMC cultures was also inhibited as
      measured by reduced accumulation of supernatant IgM and IgG. Anti-beta 2m MoAb
      did not interfere with the binding of PHA or PWM to PBMC, and membrane mobility
      as judged by subsequent capping of these lectins also appeared to be normal.
      Furthermore, anti-beta 2m was inhibitory when added 24 hr prior to peak
      responsiveness, and proliferative responses to the phorbol ester PMA in
      combination with ionomycin were also inhibited by MoAb, indicating that membrane
      mediated events were not the target of inhibition. A comparison of the inhibitory
      effects of anti-beta 2m MoAb on activation by different stimuli revealed that PWM
      and MLC responses were much more sensitive to inhibition followed by, in order of
      decreasing inhibition, Con A, PHA, ionomycin alone, and PMA/ionomycin. A MoAb to
      a monomorphic determinant of HLA-A, B, C exhibited the same inhibitory trend,
      suggesting that the mechanism of inhibition was the same as for anti-beta 2m
      MoAbs. No inhibition was observed when PBMC were stimulated by PMA alone,
      suggesting that the MoAbs have little effect on activation mediated by protein
      kinase C but may preferentially affect the calcium-dependent pathway of
      activation. Thus, this differential inhibition observed with different stimuli
      may reflect the relative contribution of class I antigens to lymphocyte
      activation by a particular mitogen.

PMID- 1991327
TI  - Thymosin alpha 1 potentiates interleukin 2-induced cytotoxic activity in mice.
AB  - We have investigated the effects of interleukin 2 (IL-2) on cytotoxic activity of
      spleen lymphocytes, from normal and cyclophosphamide (200 mg/kg) or B-16 melanoma
      suppressed mice, after in vitro or in vivo pretreatment with thymosin alpha 1
      (TA1). The results of this study indicate that pretreatment in vitro (100 ng/ml
      for 1 hr) or in vivo (200 micrograms/kg/day for 4 days) with thymosin alpha 1
      (TA1), significantly increased the IL-2 (from 100 to 500 U/ml) in vitro induced
      cytotoxic activity of spleen lymphocytes, collected from both normal and
      cyclophosphamide and tumor-suppressed animals, against both YAC-1 (NK sensitive)
      and MBL-2 (NK resistant) cell lines. The potential use in combination of these
      two different biological response modifiers, useful in enhancing the
      immunological responses to IL-2 of lymphocytes, may provide a novel model of
      immunotherapeutic intervention in cancer.

PMID- 1991329
TI  - Interaction of human peripheral blood mononuclear cells with Coccidioides immitis
      arthroconidia.
AB  - We explored the in vitro interaction of human peripheral blood mononuclear cells
      with the arthroconidial stage of the fungus Coccidioides immitis. Fresh
      peripheral blood monocytes in an adherent monolayer were capable of ingesting C.
      immitis. Further, peripheral blood monocytes from either skin-test-positive or
      skin-test-negative donors significantly decreased the in vitro growth of C.
      immitis when coccidioidal arthroconidia were incubated with monocytes. Peripheral
      blood mononuclear cells also reduced fungal incorporation of the chitin precursor
      N-acetyl glucosamine. Cell fractions consisting predominantly of monocytes were
      significantly more active in this regard than fractions containing predominantly
      lymphocytes. Moreover, this activity was independent of the coccidioidal skin
      test status of the donor. We conclude that human fresh peripheral blood
      mononuclear cells are able to phagocytize C. immitis arthroconidia and have the
      ability to inhibit its growth in vitro. That these abilities are independent of
      the immune status of the donor supports the possibility that the peripheral blood
      monocyte may contribute to the early defense against initial coccidioidal
      infection.

PMID- 1991330
TI  - The repertoire diversity and magnitude of antibody responses to bacterial
      antigens in aged mice: I. Age-associated changes in antibody responses differ
      according to the mouse strain.
AB  - Aging influences the host immune responses in various ways. In aging mice we have
      studied the antibody responses to two unrelated bacterial antigens. Streptococcus
      pneumoniae R36a vaccine (Pn) and TNP coupled to Brucella abortus (TNP-BA). Aged
      animals (20-24 months old) of the C57BL/6 strain had markedly reduced numbers of
      IgM antibody plaque-forming cells (PFC) to Pn as compared to young/adult mice (2
      3 months old). In contrast, the anti-Pn IgM PFC responses of aged BALB/c mice
      were consistently higher than they were in the young/adult mice. The increased
      anti-Pn responses were not due to a nonspecific immunostimulation, because the
      responses of aged BALB/c mice to TNP-BA were lower as compared to the adults.
      However, the aged BALB/c mice responded relatively poorly to Pn challenge, and
      their IgG responses (as determined by ELISA plaque assay) demonstrated a very
      high individual variability. The clonotypic diversity of anti-Pn response in
      young BALB/c and C57BL/6 is limited, such that the majority of PFC produce
      antibody that express all idiotopes (Id) of the T15 immunoglobulin encoded in the
      VH-S107/Vk22 genes. In contrast, the PFC from aged mice are diverse, expressing
      incomplete T15 Id or none at all, suggesting that the antibodies are encoded by
      altered T15 genes and by different, non-T15 genes. Our data demonstrate that the
      age-related changes in the magnitude of antibody response to certain antigens are
      influenced by the host genetic make-up, and that the changes in magnitude and
      diversity of antibody response may be unrelated to each other.

PMID- 1991332
TI  - Bioactivation of xenobiotics by formation of toxic glutathione conjugates.
AB  - Evidence has been accumulating that several classes of compounds are converted by
      glutathione conjugate formation to toxic metabolites. The aim of this review is
      to summarize the current knowledge on the biosynthesis and toxicity of
      glutathione S-conjugates derived from halogenated alkanes, halogenated alkenes,
      and hydroquinones and quinones. Different types of toxic glutathione conjugates
      have been identified and will be discussed in detail: (i) conjugates which are
      transformed to electrophilic sulfur mustards, (ii) conjugates which are converted
      to toxic metabolites in an enzyme-catalyzed multistep mechanism, (iii) conjugates
      which serve as a transport form for toxic quinones and (iv) reversible
      glutathione conjugate formation and release of the toxic agent in cell types with
      lower glutathione concentrations. The kidney is the main, with some compounds the
      exclusive, target organ for compounds metabolized by pathways (i) to (iii).
      Selective toxicity to the kidney is easily explained due to the capability of the
      kidney to accumulate intermediates formed by processing of S-conjugates and to
      bioactivate these intermediates to toxic metabolites. The influences of other
      factors participating in the renal susceptibility are discussed.

PMID- 1991333
TI  - Metabolism and cytotoxicity of eugenol in isolated rat hepatocytes.
AB  - The metabolism and toxic effects of eugenol (4-allyl-2-methoxyphenol) were
      studies in isolated rat hepatocytes. Incubation of hepatocytes with eugenol
      resulted in the formation of conjugates with sulfate, glucuronic acid and
      glutathione. The major metabolite formed was the glucuronic acid conjugate.
      Covalent binding to cellular protein was observed using [3H]eugenol. Loss of
      intracellular glutathione and cell death were also observed in these incubations.
      Concentrations of 1 mM eugenol caused a loss of over 90% of intracellular
      glutathione and resulted in approximately 85% cell death over a 5-h incubation
      period. The loss of the majority of glutathione occurred prior to the onset of
      cell death (2 h). The effects of eugenol were concentration dependent. The
      addition of 1 mM N-acetylcysteine to incubations containing 1 mM eugenol was able
      to completely prevent glutathione loss and cell death as well as inhibit the
      covalent binding of eugenol metabolites to protein. Conversely, pretreatment of
      hepatocytes with diethylmaleate to deplete intracellular glutathione increased
      the cytotoxic effects of eugenol. These results demonstrate that eugenol is
      actively metabolized in hepatocytes and suggest that the cytotoxic effects of
      eugenol are due to the formation of a reactive intermediate, possibly a quinone
      methide.

PMID- 1991331
TI  - Enhancement of redirected target cell lysis by cytotoxic T lymphocytes in the
      presence of cytochalasin B.
AB  - The cytochalasins are known secretogogues. Their function as such is examined in
      light of the granule exocytosis model for lymphocyte-mediated cytotoxicity.
      Cytochalasin B is found to enhance target cell lysis by cytotoxic T lymphocytes
      when antibody-coated polystyrene beads are used to bridge the cells. The pattern
      of lysis is found to be biphasic in its dependence on cytochalasin B. Secretion
      of the enzyme BLT-esterase from the effector cells parallels the cytochalasin
      concentration-dependent pattern of lysis. Cytochalasin D is also able to enhance
      lysis but at concentrations less than cytochalasin B. Cytochalasin B does not
      inhibit binding of breads to the effector cell. This is shown by the ability of
      fluorescent beads coated with antibody to bind with an appropriate specificity to
      cells. These studies indicate that cytochalasin B is not strictly inhibitory for
      the induction of target cell lysis but can enhance lymphocyte-mediated lysis at
      low drug concentrations. These results are compatible with the interpretation
      that target cell lysis is mediated through a secretion process from cytotoxic T
      lymphocytes.

PMID- 1991334
TI  - Effect of L-methionine on 2-carboxybenzaldehyde reductase induction by
      phenobarbital in primary cultures of rat hepatocytes.
AB  - Effects of phenobarbital (PB) and L-methionine on 2-carboxybenzaldehyde (CBA)
      reductase in rat hepatocyte primary culture were examined. Inclusion of PB in the
      culture medium markedly enhanced the CBA reductase activity while L-methionine,
      which elevates the cellular glutathione (GSH) level, suppressed the stimulatory
      effect of PB. This suppression, though less pronounced, was also found with other
      precursors of GSH biosynthesis. GSH-depletors, buthionine sulfoximine (BSO) or
      diethylmaleate (DEM), enhanced the CBA reductase activity suggesting that GSH
      plays an important role in enzyme induction.

PMID- 1991335
TI  - Sulfur-containing proreactive intermediates: hydrolysis and mutagenicity of
      halovinyl 2-nitrophenyl disulfides.
AB  - Chemical cleavage of the sulfur-sulfur bond in halovinyl and fluoroalkyl 2
      nitrophenyl disulfides is expected to yield halovinyl and fluoroalkyl thiols
      identical to those formed by cysteine conjugate beta-lyase catalyzed cleavage of
      the corresponding cysteine S-conjugates. To study the potential use of disulfides
      as precursors for these thiols, whose transformation to acylating agents is most
      likely responsible for cysteine S-conjugate mutagenicity, we determined the
      mutagenicity of several halovinyl and fluoroalkyl 2-nitrophenyl disulfides and
      identified products formed by hydrolysis of these disulfides, 1,2,3,4,4
      Pentachlorobutadienyl 2-nitrophenyl disulfide, 1,2,2-trichlorovinyl 2-nitrophenyl
      disulfide, 1-fluro-2,2-dichlorovinyl 2-nitrophenyl disulfide and 1,2-dichloro
      3,3,3-trifluropropenyl 2-nitrophenyl disulfide were mutagenic in nitroreductase
      deficient strains of Salmonella typhimurium TA100; as haloalkyl cysteine S
      conjugates, 1,1-difluoro-2,2-dichloroethyl 2-nitrophenyl disulfide and 1-chloro
      1,2,2-trifluroethyl 2-nitrophenyl disulfide were not mutagenic. Hydrolysis of
      1,2,3,4,4-pentachlorobutadienyl 2-nitrophenyl disulfide and 1,2,2-trifluorethyl 2
      nitrophenyl disulfide in presence of diethylamine resulted in
      tetrachlorothiobutenoic acid diethylamide and chlorofluorothionoacetic acid
      diethylamide. The differences in mutagenicity between halovinyl and fluoroalkyl
      disulfides are most likely responsible to their different abilities to react with
      DNA-constituents. Products formed from the mutagenic 1,2,3,4,4
      pentachlorobutadienyl 2-nitrophenyl disulfide modified 2'-deoxyguanosine-3'
      monophosphate and DNA as detected by 32Phosphorus-postlabeling, whereas products
      formed from the nonmutagenic 1-chloro-1,2,2-trifluoroethyl 2-nitrophenyl
      disulfide did not result in detectable 2'-deoxyguanosine-3'-monophosphate and DNA
      modification.

PMID- 1991336
TI  - Evaluation of the antioxidant properties of thyroid hormones and propylthiouracil
      in the brain-homogenate autoxidation system and in the free radical-mediated
      oxidation of erythrocyte membranes.
AB  - The antioxidant capacity of thyroid hormones and the antithyroid drug
      propylthiouracil was studied in three model systems, namely, autoxidation of rat
      brain homogenates and oxidation of rat erythrocyte plasma membranes (EPM) induced
      by either 2,2'-azobis-(2-amidinopropane) (AAP) thermolysis or by gamma
      irradiation. Thyroid hormones significantly inhibited the development of lipid
      peroxidation in these systems at micromolar concentrations, as assessed either by
      visible light emission, thiobarbituric acid reactive substances accumulation or
      oxygen uptake. This behaviour was not observed when L-3,3',5-triiodothyronine
      (T3) and L-thyroxine (T4) were assayed at nanomolar concentrations. In EPM
      exposed to AAP or gamma irradiation, propylthiouracil inhibited the induced lipid
      peroxidation, with Q1/2 values of 112-150 microM. It is concluded that the
      antioxidant capacity of thyroid hormones found in vitro may not be of relevance
      in physiological conditions, which exhibit variations of T3 and T4 levels in the
      nanomolar range. On the other hand, the behaviour of propylthiouracil as an
      inhibitor of EPM lipid peroxidation is observed at concentrations close to the
      therapeutic levels, thus representing a possible complementary action to its
      antithyroid activity.

PMID- 1991337
TI  - Ionic and radical oxidations of DNA by hydrogen peroxide.
AB  - Hydrogen peroxide mediated oxidation of 2'-deoxyadenosine and isolated DNA was
      investigated. Reaction of hydrogen peroxide with 2'-deoxyadenosine under non
      radical conditions led to the formation of a predominant decomposition product.
      This was identified as 2'-deoxyadenosine N-1-oxide on the basis of detailed 1H
      and 13C NMR analysis and further confirmed by photolysis experiments.
      Quantitative determination of both radical and ionic DNA type damage was based on
      the use of a 32P-postlabeling method (5-hydroxymethyluracil and adenine N-1
      oxide) and of an HPLC-EC assay (8-hydroxyguanine). Adenine N-1-oxide was shown to
      be the predominant ionic DNA base damage under non radical conditions. The
      presence of Fe(II)-DTPA complex in the reaction medium led to a reduction in the
      amount of adenine N-1-oxide by a factor of 4 whereas radical DNA type damages
      including 8-hydroxyguanine and 5-hydroxymethyluracil was increased by a factor of
      2-3.

PMID- 1991338
TI  - Metabolism of chrysene, 5-methylchrysene, 6-methylchrysene and 5,6
      dimethylchrysene in rat liver cytosol, in vitro, and in rat subcutaneous tissue,
      in vivo.
AB  - The polynuclear aromatic hydrocarbon chrysene undergoes a bioalkylation
      substitution reaction in vitro, in rat liver cytosol preparations, and in vivo,
      in rat dorsal subcutaneous tissue to yield 6-methylchrysene as a metabolite. In
      addition, both 5-methyl- and 6-methylchrysene were found to undergo a
      dealkylation reaction in these tissues to yield chrysene as well as both a
      biooxidation reaction to yield the corresponding hydroxyalkyl substituted
      chrysene and a bioalkylation reaction to give a dimethyl substituted chrysene. 5
      Methylchrysene enzymatically cyclized to the 4,5-methylenechrysene derivative, an
      analog of benzo[a]pyrene in these tissues. 5,6-Dimethylchrysene was metabolized
      to monomethyl chrysenes, chrysene, and the hydroxyalkyl substituted chrysenes.
      The results suggest that chemical or biochemical substitution of a methyl group
      at the center of highest biochemical reactivity may be a necessary step in the
      metabolic activation and carcinogenicity of these compounds and their methylene
      bridged metabolites.

PMID- 1991339
TI  - Alkylation of nucleic acids by DNA-targeted 4-anilinoquinolinium aniline
      mustards: kinetic studies.
AB  - The rate of constant for hydrolysis of a series of 4-substituted aniline mustards
      Ar-X-pC6H4-N(CH2CH2Cl)2, where Ar is 4-anilinoquinolinium and X = O, CH2, CONH
      and CO, have been measured in water and 0.02 M imidazole buffer at 37 degrees C
      and in 50% aqueous acetone at 66 degrees C. The equilibrium binding constants of
      the compounds and their hydrolysis products to nucleic acids of differing base
      composition have been determined at varying ionic strengths, and the results are
      consistent with the compounds binding as expected in the DNA minor groove. The
      alkylating reactivity of the mustards towards these nucleic acids has been
      measured in water at 37 degrees C and in 0.01 M HEPES buffer over a range of
      temperatures from 25 degrees C to 60 degrees C. Evaluation of the thermodynamic
      parameters for these kinetic and equilibrium studies suggests that the
      interaction with nucleic acids is via an internal SN2 mechanism involving an
      aziridinium ion.

PMID- 1991340
TI  - Membrane potential fluctuations and transient inward currents induced by reactive
      oxygen intermediates in isolated rabbit ventricular cells.
AB  - The cellular basis of reactive oxygen intermediate-induced arrhythmias was
      investigated in isolated rabbit ventricular cells using the whole-cell voltage-
      and current-clamp techniques. Singlet oxygen and superoxide were generated by the
      photoactivation of rose bengal. Single ventricular cells exposed to rose bengal
      (10-100 nM) exhibited spontaneous membrane potential fluctuations at plateau
      potentials and at the level of the resting membrane potential. The voltage
      fluctuations induced in the resting potential occasionally triggered repetitive
      action potential discharges. At the resting membrane potential, the magnitude and
      dominant frequency of the voltage fluctuations were 1-3 mV and 1.5 Hz,
      respectively. At plateau potentials, the amplitude of the voltage fluctuations
      was about 2-5 mV, and the dominant oscillatory frequency was 2.6 Hz. In voltage
      clamp experiments, transient inward currents were induced on repolarization after
      a depolarizing clamp step. Oscillatory currents also occurred occasionally during
      clamp steps to positive potentials. The peak frequencies of transient inward
      currents recorded at -20 and -70 mV were approximately 3.7 and 2.3 Hz,
      respectively, indicating that these currents may underlie the arrhythmogenic
      membrane potential fluctuations observed in current-clamp experiments. The rose
      bengal-induced transient inward currents were shown to be dependent on the
      magnitude and duration of the preceding voltage step. Studies of the voltage
      dependence of transient inward currents showed that these currents remained
      inward even at positive potentials (+30 mV), and replacement of extracellular
      sodium with lithium decreased transient inward current to approximately 10% of
      its initial value. Thus, the major component of oxidant stress-induced inward
      current appears to be electrogenic Na-Ca exchange. This oscillatory transient
      inward current may be responsible for the arrhythmias induced in isolated hearts
      exposed to reactive oxygen intermediates, and since oxidant stress has been
      implicated in reperfusion injury, it is possible that similar oscillatory
      currents may underlie reperfusion-induced arrhythmias.

PMID- 1991341
TI  - Putative mechanisms of the impairment of endothelium-dependent relaxation of the
      aorta with atheromatous plaque in heritable hyperlipidemic rabbits.
AB  - Attenuation of acetylcholine-induced endothelium-dependent relaxation of thoracic
      aortas excised from Watanabe heritable hyperlipidemic (WHHL) rabbits linearly
      correlated with the percent area coated with atheromatous plaque. To elucidate
      mechanisms related to this reduced endothelium-dependent relaxation in the
      presence of atherosclerosis, the acetylcholine-induced release of endothelium
      derived relaxing factor (EDRF) was assessed functionally as a percent relaxation
      of the precontracted detector strips obtained from the tunica media beneath the
      intact intima or the atheromatous plaque in the same aortic ring preparation.
      Relaxations of the normal detectors to effluents containing EDRF of thoracic
      aortas during stimulation by acetylcholine (3 x 10(-6) M) in heterozygous and
      homozygous WHHL rabbits were 73 +/- 5% and 59 +/- 9% (p less than 0.01) of the
      phenylephrine-induced precontraction, respectively. Relaxations of the
      atherosclerotic detectors to effluents (EDRF) through the aortas during
      stimulation by acetylcholine (3 x 10(-6) M) in heterozygous and homozygous WHHL
      rabbits were 16 +/- 4% and 14 +/- 5%, respectively--values significantly smaller
      than those seen in the normal detectors. When superoxide dismutase was added to
      the perfusate of the donors from homozygous and heterozygous WHHL rabbits,
      atherosclerotic detectors relaxed by effluents stimulated by acetylcholine to 73%
      and 65% (p less than 0.01 versus before the addition of superoxide dismutase) of
      the normal detector, respectively. Relaxations induced by sodium nitroprusside as
      well as the contractions by acetylcholine, phenylephrine, and KCl (118 mM) were
      comparable in detector strips from the normal and atherosclerotic portions. Thus,
      not only is the amount of EDRF released by acetylcholine reduced in the presence
      of atherosclerosis, the tunica media beneath the atheromatous plaque is also to
      some extent responsible for the superoxide-induced inactivation of EDRF.

PMID- 1991342
TI  - Effects of local reduction in pressure on distensibility and composition of
      cerebral arterioles.
AB  - This study examined effects of local reductions in mean and pulse pressures on
      cerebral arterioles in normotensive Wistar-Kyoto rats (WKY) and stroke-prone
      spontaneously hypertensive rats (SHRSP). WKY and SHRSP underwent clipping of one
      carotid artery at 1 month of age. At 10-12 months of age, mechanics of pial
      arterioles were examined in vivo in anesthetized rats. Bilateral craniotomies
      were performed to expose pial arterioles in the sham and clipped cerebral
      hemispheres. Stress-strain relations were calculated from measurements of pial
      arteriolar pressure (servo null), diameter, and cross-sectional area of the
      arteriolar wall. Point counting stereology was used to quantitate individual
      components in the arteriolar wall. Before deactivation of smooth muscle with
      EDTA, mean (Pm) and pulse (Pp) pressures were significantly less (p less than
      0.05) in clipped than in sham arterioles in WKY (Pm, 63 +/- 2 versus 73 +/- 2 mm
      Hg; Pp, 23 +/- 3 versus 30 +/- 3 mm Hg) and SHRSP (Pm, 94 +/- 4 versus 110 +/- 4
      mm Hg; Pp, 27 +/- 2 versus 38 +/- 3 mm Hg). Cross-sectional area of the
      arteriolar wall was less (p less than 0.05) in clipped than in sham arterioles in
      both groups of rats (1,403 +/- 125 versus 1,683 +/- 125 microns2 in WKY; 1,436 +/
      72 versus 1,926 +/- 134 microns2 in SHRSP). There was a correlation between
      cross-sectional area of the vessel wall and pulse pressure (r2 = 0.66), but not
      mean pressure (r2 = 0.09). During maximal dilatation with EDTA, the stress-strain
      curve was shifted to the left in clipped arterioles of SHRSP, but not of WKY,
      which indicates that carotid clipping in SHRSP reduces passive distensibility of
      cerebral arterioles. The proportion of distensible components in the vessel wall
      (smooth muscle, elastin, and endothelium) was reduced in clipped arterioles in
      SHRSP, but not in WKY. These findings suggest that 1) vascular hypertrophy of
      cerebral arterioles is related more closely to pulse pressure than to mean
      pressure, and 2) reduction of pial arteriolar pressure completely prevents
      cerebral vascular hypertrophy and attenuates increases in passive distensibility
      of cerebral arterioles in SHRSP.

PMID- 1991343
TI  - Protein kinase C modulates basal myogenic tone in resistance arteries from the
      cerebral circulation.
AB  - The objective of this study was to determine whether myogenic tone in the
      cerebral circulation can be modified by agents that interact with protein kinase
      C (PKC), a modulator of intracellular calcium sensitivity. Pial arteries (194 +/-
      8 microns at 125 mm Hg) were isolated from Wistar-Kyoto rats and mounted on glass
      microcannulas in a specialized arteriograph. Simultaneous recordings of
      transmural pressure and lumen diameter were made with a video-electronic system.
      Myogenic tone, which developed at transmural pressures above 50 mm Hg, reduced
      lumen diameter by 29 +/- 3%, to 136 +/- 5 microns. Staurosporine (a PKC
      inhibitor) or indolactam (a PKC activator) was added cumulatively to segments of
      arteries obtained from each animal. Staurosporine induced progressive and
      eventually complete dilation, with half-maximal inhibition of myogenic tone
      occurring at a concentration of 1.32 +/- 0.10 nM. Conversely, indolactam
      augmented basal tone, reducing diameter by a maximum of 62 +/- 3%, with half
      maximal effects at 0.4 +/- 1.0 microM. The effects of indolactam on arterial
      responses to acute increases in transmural pressure were also determined to test
      whether this dynamic and possibly separate mechanism could be potentiated by PKC
      stimulation. Although basal tone was augmented, diameter responses to increased
      pressure were not altered. In summary, these results implicate PKC in the
      regulation of basal myogenic tone and resistance artery caliber, which is a major
      determinant of blood flow. PKC modulation did not affect diameter responses to
      sudden changes in transmural pressure, however, suggesting the existence of a
      separate sensing/transduction mechanism that has yet to be identified.

PMID- 1991344
TI  - Transmural myocardial deformation in the ischemic canine left ventricle.
AB  - The myocardium is a complex three-dimensional structure consisting of myocytes
      interconnected by a dense collagen weave that courses in different directions.
      Regional ischemia can be expected to produce complex changes in ventricular
      deformation. In the present study, we examined the effects of ischemia on two-
      and three-dimensional finite strains during acute transmural myocardial ischemia
      in 13 open-chest anesthetized dogs. In contrast to systolic deformation observed
      during the control period in which circumferential shortening exceeded
      longitudinal shortening, our results indicate that after 5 minutes of acute
      ischemia, end-systolic in-plane lengthening across the left ventricular wall
      occurs in approximately equal amounts in the circumferential and longitudinal
      directions. Along with these changes in extensional strains, there were
      significant negative transverse shearing deformations during ischemia. Myocardial
      ischemia also resulted in a loss of the normal end-systolic transmural gradients
      of shortening and thickening. Three-dimensional end-diastolic strains indicate
      that the left ventricular wall undergoes a significant passive reconfiguration
      that varies transmurally with lengthening in the epicardial tangent plane and
      wall thinning increasing from the epicardium toward the endocardium. The large
      systolic changes in shearing deformations with ischemia could potentially
      influence collateral blood flow and certainly indicate that uniaxial measurements
      of deformation in the ischemic myocardium, which do not account for shearing
      deformation, are incomplete and must be interpreted with caution. Moreover,
      normal transmural systolic gradients in deformation, which would be anticipated
      on geometric grounds, are lost during ischemia, implying that the material
      properties of ischemic tissue or the loading conditions imposed on the ischemic
      region by partially impaired adjacent myocardium vary transmurally.

PMID- 1991345
TI  - Tone-dependent waterfall behavior during venous pressure elevation in isolated
      canine hearts.
AB  - We examined the "vascular waterfall" hypothesis, which proposes that coronary
      flow is unaffected by elevations in outflow pressure until the latter reaches a
      critical threshold level, in 29 isolated canine hearts. In fibrillating hearts
      vasodilated with adenosine or carbocromen, coronary flow and the coronary
      pressure-flow relation were not affected by changes in great cardiac vein
      pressure (PGCV) below a threshold value of 11 +/- 0.9 (mean +/- SEM) mm Hg.
      Further elevations of PGCV reduced flow and shifted the pressure-flow relation to
      the right, increasing its pressure-axis intercept (Pf=0). When vasomotor tone was
      augmented with vasopressin, threshold PGCV increased to 25 +/- 2.7 mm Hg (p less
      than 0.001). Once again, the pressure-flow relation was unaffected by changes in
      PGCV below the threshold value and shifted to the right when this value was
      exceeded. The amount by which spontaneous values of Pf=0 exceeded threshold
      values of PGCV was greater when vasomotor tone was augmented than during
      vasodilation. Pf=0 continued to exceed PGCV when the latter was raised above the
      threshold level. Both Pf=0 and threshold values of PGCV were less during a long
      diastole than during ventricular fibrillation. We reached the following
      conclusions. 1) During changes in PGCV below a threshold value, the coronary
      circulation exhibits traditional waterfall behavior. 2) The threshold pressure
      for altering waterfall behavior is affected by vascular tone and mechanical
      activity. 3) Pf=0 remains above PGCV when the latter is increased above the
      threshold value needed to alter flow.

PMID- 1991346
TI  - Free radicals mediate actions of oxyhemoglobin on cerebrovascular smooth muscle
      cells.
AB  - Single smooth muscle cells were isolated from the basilar artery of the rat by
      enzymatic dispersion. The membrane properties of the cells were assessed using
      the patch-electrode voltage-clamp technique, and cell viability was monitored
      using fluorescein diacetate uptake. Exposure of the cells to oxyhemoglobin (5
      microM) resulted in 1) contraction, 2) the appearance of membrane blebs, 3) an
      increase in the outward potassium currents, 4) a decrease in the membrane
      resistance, and 5) cell death. In contrast, no effect of oxyhemoglobin on
      cultured murine neuroblastoma cells was observed. Methemoglobin (100 microM) had
      no effects on the smooth muscle cells. Catalase (300 units/ml) or dimethyl
      sulfoxide (0.5%) protected against the effects of oxyhemoglobin; superoxide
      dismutase (100-1,000 units/ml) provided only partial protection. Exposure of the
      cells to superoxide anions generated by xanthine (1 mM) plus xanthine oxidase (10
      units/l) or to hydrogen peroxide (500 microM) caused an increase in the outward
      potassium currents without affecting membrane resistance. Generation of hydroxyl
      radicals by metal ions plus hydrogen peroxide caused the same effects as
      oxyhemoglobin, that is, an increase in the potassium currents, followed by a
      decrease in the membrane resistance and cell death. In conclusion, it appears
      that oxyhemoglobin exerts its effects on vascular smooth muscle cells by the
      generation of free radicals, chiefly hydroxyl radicals.

PMID- 1991347
TI  - Calcium-activated chloride current in rabbit ventricular myocytes.
AB  - We have used the whole-cell patch-clamp technique to examine the ionic basis for
      a transient outward current in rabbit ventricular myocytes. High concentrations
      of intracellular calcium buffer prevented the current, isoproterenol increased
      it, and cadmium, nisoldipine, ryanodine, or caffeine blocked it. These data are
      consistent with a current that is calcium activated, by the calcium transient
      that causes contraction. The current was not blocked by external 4-aminopyridine
      or tetraethylammonium, and it was still present if external potassium was omitted
      and internal potassium was replaced by cesium. The current was absent when
      intracellular and extracellular chloride concentrations were drastically reduced,
      even when intracellular and extracellular potassium concentrations were normal.
      The current was blocked by the anion transport blockers 4-acetamido-4'
      isothiocyanatostilbene-2,2'-disulfonic acid (SITS) and 4,4'
      diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) and responded to
      extracellular chloride changes as expected for a chloride current. We used SITS
      and DIDS to define the voltage dependence of the transient outward current. The
      current first appeared at voltages positive to the threshold of the calcium
      current and declined as voltage approached the calcium reversal potential. Tail
      current experiments suggested that the current rectified strongly in the outward
      direction. We propose that the 4-aminopyridine-resistant transient outward
      current of rabbit ventricular myocytes is a calcium-activated chloride current.

PMID- 1991348
TI  - Conditioning prepulse of biphasic defibrillator waveforms enhances refractoriness
      to fibrillation wavefronts.
AB  - The mechanism of biphasic waveform defibrillation threshold reduction is unknown.
      We tested the hypothesis that, during refractory period stimulation, sarcolemmal
      hyperpolarization by the first pulse of biphasic waveforms facilitates excitation
      channel recovery, which enhances graded responses produced by the second
      depolarizing pulse. This prolongs cellular refractoriness to fibrillation
      wavefronts when compared with a monophasic depolarizing stimulus. Monophasic (10
      msec, rectangular wave) or symmetrical biphasic (10 msec, each pulse) current
      injection S2 stimuli at 1.5 and two times S1 threshold were used to scan the S1
      action potential refractory period (S1 cycle length, 600 msec) in myocardial cell
      aggregates. S2 waveforms were delivered with normal and reversed polarity to test
      the hyperpolarizing action of biphasic waveforms. Responses to an S3 stimulus,
      which simulated a potential incoming fibrillation wavefront, were also
      determined. Results showed that biphasic S2 waveforms produced longer graded
      responses during and immediately after the S1 refractory period than did
      corresponding monophasic S2 waveforms. The maximum difference in response
      duration produced by the biphasic and monophasic waveforms was 58.6 +/- 10.0 msec
      (p less than 0.001). This maximum difference occurred 10 msec before the end of
      the S1 refractory period. The longer response durations produced by biphasic S2
      also produced longer refractoriness to the S3 stimulus. The maximum difference in
      total refractoriness to S3 of 51.8 +/- 2.8 msec (p less than 0.002) occurred at
      the same S1S2 coupling interval as the maximum difference in S2 response
      duration. Prolonged refractoriness may protect ventricular cells from
      refibrillation wavefronts and act as the cellular basis for greater biphasic
      waveform defibrillation efficacy.

PMID- 1991349
TI  - Angiotensin II induces smooth muscle cell proliferation in the normal and injured
      rat arterial wall.
AB  - The present study was undertaken to explore the possibility that neointimal
      smooth muscle cells, the characteristic cells of restenosis and atherosclerosis,
      are selectively stimulated to replicate by a hypertensive stimulus. Angiotensin
      II (AII) was infused by osmotic minipumps for 2 weeks in 4.5-month-old rats.
      Group A received AII (200 ng/min) 2 weeks after a balloon catheter-induced injury
      of the thoracic aorta and left common carotid artery. Group B received only AII,
      group C only balloon denudation, and group D neither balloon injury nor AII.
      During the AII or Ringer's solution infusion, all animals received [3H]thymidine
      via a second minipump to measure DNA synthesis. AII increased the systolic
      pressure by more than 40 mm Hg. AII significantly increased DNA synthesis in the
      media of the carotid artery from 0.2 +/- 0.2% in group C to 2.5 +/- 1.5% in group
      A (mean +/- SD, n = 5 or 6). DNA synthesis in the neointima of the carotid artery
      significantly increased with AII from 4.8 +/- 4.2% in group C to 19.8 +/- 13.9%
      in group A. Cross-sectional area of the neointima almost doubled during AII
      infusion, and it increased approximately 25% in the media. Comparable results
      were obtained in the aorta. In a second experiment, AII was infused (125 ng/min)
      for 2 weeks in 11-week-old rats. Concomitantly, [3H]thymidine was given. Control
      rats received Ringer's solution and [3H]thymidine in their pumps. Blood pressures
      were elevated to the same extent as in the older animals.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1991350
TI  - Effects of antibodies to myosin light chain kinase on contractility and myosin
      phosphorylation in chemically permeabilized smooth muscle.
AB  - We have used an immunological approach to investigate the role of myosin light
      chain phosphorylation (MLC-Pi) in the control of contractility in smooth muscle.
      Our aim was to specifically inhibit myosin light chain kinase (MLCK) in the
      presence of physiologically activating levels of Ca2+ so that other putative
      Ca2(+)-dependent regulatory systems could be unmasked. Fab fragments were
      prepared by papain digestion of immunoglobulin G (IgG) molecules obtained from
      goats immunized with turkey gizzard MLCK. Anti-MLCK Fab was then purified by
      chromatography on an MLCK-Sepharose 4B column. These affinity-purified Fab
      fragments inhibit the activity of MLCK purified from turkey gizzard smooth muscle
      and interact monospecifically with MLCK in various mammalian smooth muscles as
      demonstrated by a Western blot analysis. The effect of these Fab fragments on the
      contractile properties was tested in guinea pig taenia coli made permeable
      (skinned) using Triton X-100. Skinned fibers, approximately 100 microns in
      diameter and 4 mm long, were mounted for isometric measurements and immersed in
      calcium-EGTA buffers. Fibers preincubated with anti-MLCK Fab in relaxing solution
      (Ca2+ less than 1 nM) for 75 minutes developed about 25% of the isometric force
      of a parallel control contraction when transferred to contracting solution (Ca2+
      = 0.5 microM). When added to contracting solution at the peak of a contracture,
      anti-MLCK Fab elicited a relaxation that was complete in about 120 minutes
      despite the presence of Ca2+. No significant effect on isometric force was
      observed when fibers were incubated with another affinity-purified mouse Fab
      raised against the Fc region of human IgG (control Fab).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1991352
TI  - Spontaneous termination of reentry after one cycle or short nonsustained runs.
      Role of oscillations and excess dispersion of refractoriness.
AB  - This study describes factors that contribute to spontaneous termination of
      reentry lasting one to 10 cycles after induction by a single premature stimulus.
      Reentry was studied in vitro in rings of canine atrial tissue from around the
      tricuspid valve orifice. Activation was recorded from a circular array of 10
      extracellular bipolar electrodes equally spaced around the ring. In some
      experiments, transmembrane or monophasic action potential recordings were made
      near critical sites. Termination of reentry within one cycle after induction was
      recorded 110 times in 11 of 35 experiments. Important factors contributing to
      termination were 1) an obligatory reversal of the activation sequence that
      resulted in a long coupling interval in the critical region beyond the site of
      unidirectional block after the premature stimulus and 2) much longer refractory
      periods limited to this critical region, which facilitated unidirectional block
      but contributed to termination when this region was first activated with a short
      coupling interval at the end of the first reentrant cycle. Termination of
      nonsustained reentry lasting longer than one cycle resulted from oscillations of
      conduction and refractoriness initiated by the abrupt shortening of cycle length
      after initiation of reentry. Oscillations of conduction resulted from interval
      dependent conduction of reentrant impulses that encountered partially refractory
      tissue. For reentry to become sustained, the oscillations after induction of
      reentry must dampen. Thus, damped cycle length oscillations after induction may
      identify clinical tachycardias caused by reentry with a partially excitable gap.

PMID- 1991351
TI  - Protective effect of increased glycolytic substrate against systolic and
      diastolic dysfunction and increased coronary resistance from prolonged global
      underperfusion and reperfusion in isolated rabbit hearts perfused with
      erythrocyte suspensions.
AB  - Current therapy of myocardial infarction may include early reperfusion. We
      simulated myocardial perfusion conditions during evolving myocardial infarction
      in isolated, normothermic, isovolumic rabbit hearts perfused with buffer
      containing bovine red blood cells (hematocrit of 40%), and we assessed the
      effects of high levels of glucose and insulin as "therapy" during prolonged (150
      minute) severe underperfusion and reperfusion. Protocol 1 consisted of
      underperfusion at a constant coronary perfusion pressure of 8 mm Hg. The control
      group (n = 8) received 5.5 mmol/l glucose and 15 microunits/ml insulin; the group
      treated with high levels of glucose and insulin (G + I) (n = 8) received 19.5
      mmol/l glucose and 250 microunits/ml insulin during both underperfusion and
      reperfusion. Relative to the control group, the G + I group experienced 1)
      greater developed pressure during underperfusion and increased recovery during
      reperfusion, 2) preserved diastolic function during underperfusion and
      reperfusion, 3) lower coronary resistance and greater coronary flow during the
      underperfusion period, 4) increased glycolytic flux and preserved glycogen stores
      and high energy phosphate levels, and 5) less loss of myocyte enzymes (creatine
      kinase and alanine aminotransferase). In protocol 2, coronary flow was kept
      identical in control (n = 8) and G + I hearts (n = 8) during the underperfusion
      period, and left ventricular end-diastolic pressure was kept below 10 mm Hg in
      both groups to minimize subendocardial damage and vascular compression. In this
      protocol, the effect of the G + I intervention in the prevention of an increase
      in coronary resistance during the underperfusion period was distinguished from
      its myocellular metabolic effects; the high G + I substrate had protective
      effects on mechanical and metabolic function that were less marked than, but
      similar to, those in protocol 1, indicating that its mechanisms of protection
      during underperfusion affected both cardiac function and coronary resistance. We
      conclude that the G + I intervention, in clinically relevant concentrations,
      markedly protected severely underperfused myocardium for 150 minutes and may be a
      beneficial intervention in combination with reperfusion therapy in acute
      myocardial infarction.

PMID- 1991353
TI  - Human leukoagglutinating antibody evokes cooperative leukotriene synthesis in
      pulmonary microvasculature. Model of transfusion-related acute lung injury.
AB  - Leukoagglutinating antibodies have been implicated in the development of
      transfusion-related acute lung injury. In the present study, human neutrophil
      leukotriene generation was provoked by an anti-5b immunoglobulin G, isolated from
      a multiparous donor plasma that caused noncardiogenic lung edema during
      transfusion therapy. In 5b-positive polymorphonuclear neutrophils (PMNs), the
      antibody stimulated marked arachidonic acid metabolism, dependent on the presence
      of plasma as the complement source. Quantity and profile of lipid mediators
      (leukotriene B4 and its omega-oxidation products, 5-hydroxyeicosatetraenoic acid,
      and nonenzymatic hydrolysis products of leukotriene A4) corresponded to those
      repeatedly described after PMN in vitro stimulation with the artificial calcium
      ionophore A23187. Anti-5b challenge of PMNs sequestered in the microvasculature
      of perfused rabbit lungs did, however, induce a markedly modified metabolite
      profile. Nonenzymatic hydrolysis products of leukotriene A4 were not detected,
      and 5-hydroxyeicosatetraenoic acid was markedly reduced. In contrast, cysteinyl
      leukotrienes were measured as predominant compounds, with rapid appearance of
      leukotriene C4 and more protracted generation of leukotriene E4. Leukotriene B4
      and its omega-oxidation products were released with similar kinetics, but in
      lower amounts, as compared with the isolated PMN stimulation. Anti-5b challenge
      of PMNs coincubated with pulmonary artery endothelial cells in vitro, but not
      stimulation of either cell type alone, provoked marked generation of cysteinyl
      leukotrienes. These findings suggest modulation of PMN 5-lipoxygenase metabolism
      in favor of leukotriene A4 transfer to adjacent acceptor cells with subsequent
      enzymatic conversion to cysteinyl leukotrienes under conditions of lung vascular
      sequestration. Endothelial cells appear to serve as predominant cooperative cells
      under circumstances of blood-free lung perfusion. PMN-related transcellular
      eicosanoid synthesis may be involved in the pathogenesis of transfusion-evoked
      acute lung injury.

PMID- 1991354
TI  - Virtual cathode effects during stimulation of cardiac muscle. Two-dimensional in
      vivo experiments.
AB  - We have found that when suprathreshold cathodal stimuli were applied to the
      epicardium of canine ventricle, impulse propagation originated at a "virtual
      cathode" with dimensions greater than those of the physical cathode. We report
      the two-dimensional geometry of the virtual cathode as a function of stimulus
      strength; the results are compared with the predictions of an anisotropic,
      bidomain model of cardiac conduction recently developed in our laboratories. Data
      were collected in six pentobarbital-anesthetized dogs by using a small plaque
      electrode sewn to the left ventricular epicardium. Arrival times at closely
      spaced bipolar electrodes oriented radially around a central cathode were
      obtained as a function of stimulus strength and fiber orientation. The dimensions
      of the virtual cathode were determined by linear back-extrapolation of arrival
      times to the time of stimulation. The directional dependence of the conduction
      velocity was consistent with previous reports: at 1 mA, longitudinal (0 degree)
      and transverse (90 degrees) velocities were 0.60 +/- 0.03 and 0.29 +/- 0.02
      m/sec, respectively. At 7 mA, the longitudinal velocity was 0.75 +/- 0.05 m/sec,
      whereas there was no significant change in the transverse velocity. In contrast
      to conduction velocity, the virtual cathode was smallest in the longitudinal
      orientation and largest between 45 degrees and 60 degrees. Virtual cathode size
      was dependent on both orientation and stimulus strength: at 0 degree, the virtual
      cathode was small (approximately 1 mm) and relatively constant over the range of
      1-7 mA; at oblique orientations (45 degrees-90 degrees), it displayed a roughly
      logarithmic dependence on stimulus strength, approximately 1 mm at 1 mA and
      approximately 3 mm at 7 mA. The bidomain, anisotropic model reproduced both the
      stimulus strength and the fiber-orientation dependence of the virtual cathode
      geometry when the intracellular and extracellular anisotropies were 10:1 and 4:1,
      respectively, but not when the two anisotropies were equal. We suggest that the
      virtual cathode provides a direct measure of the determinants of cardiac
      activation; its complex geometry appears to reflect the bidomain, anisotropic
      nature of cardiac muscle.

PMID- 1991355
TI  - Changes in diastolic cardiac function in developing and stable perinephritic
      hypertension in conscious dogs.
AB  - The effects of developing perinephritic hypertension (2-3 weeks) and a more
      stable period of perinephritic hypertension (approximately 14 weeks) were
      examined on indexes of left ventricular (LV) diastolic function in conscious,
      chronically instrumented dogs. The complete period of diastole was studied using
      indexes of isovolumic relaxation (tau), early filling (LV +dD/dt), and stiffness
      (myocardial stiffness and chamber stress/diameter ratio). During developing
      hypertension, increased LV end-diastolic pressure, LV end-diastolic stress, peak
      filling rate, myocardial stiffness, and the stress/diameter ratio increased (p
      less than 0.05); the time constant tau was not changed. These changes were
      associated with preserved baseline levels of coronary blood flow (radioactive
      microspheres) but an impaired coronary vasodilator response to adenosine. Acute
      administration of phenylephrine in the normotensive dogs caused increases in
      systolic and diastolic stress and resulted in increases in myocardial stiffness
      and in the stress/diameter ratio similar to values observed in developing
      hypertension. During stable hypertension, LV end-diastolic stress, peak filling
      rate, and both parameters of late-diastolic function (myocardial stiffness and
      stress/diameter ratio) returned toward control values, but the isovolumic
      relaxation time constant was increased. Quantitative histological evaluation
      revealed no increase in stainable connective tissue in dogs with stable
      hypertension compared with control dogs, and hydroxyproline concentration was not
      increased in the subendomyocardium, midmyocardium, or subepimyocardium of the
      dogs with chronic perinephritic hypertension. Thus, in developing hypertension,
      major alterations in diastolic function were observed that were not structurally
      related, since these changes 1) could be induced in normal dogs by increasing
      preload and afterload acutely with phenylephrine and 2) were improved during the
      ensuing stable period of hypertension.

PMID- 1991356
TI  - Effects of inosine on glycolysis and contracture during myocardial ischemia.
AB  - The effects of inosine (INO) on substrate metabolism and rigor formation in
      ischemic myocardium were examined in isolated rabbit hearts. Metabolite content
      was assessed in tissue extracts by chemical analysis and in the whole heart by
      13C and 31P nuclear magnetic resonance spectroscopy. In ischemic hearts
      metabolizing either [3-13C]pyruvate or [1-13C]glucose, 1 mM INO increased both
      total and 13C-labeled alanine content; lactate content was unaffected. At 3
      minutes of ischemia, tissue alanine was 1.81 +/- 0.11 microM/g wet wt (mean +/-
      SEM) in hearts perfused with pyruvate+INO versus 1.23 +/- 0.15 microM/g wet wt in
      hearts perfused with pyruvate alone (p less than 0.05). INO reduced tissue
      glycogen during ischemia in pyruvate-perfused hearts. Tissue alanine content in
      ischemic hearts that were supplied glucose+INO (1.29 +/- 0.13 microM/g wet wt)
      was greater than in ischemic hearts supplied glucose alone (0.65 +/- 0.14
      microM/g wet wt). Alanine was found to originate from pyruvate and was a
      glycolytic end product in glucose-perfused hearts. INO raised the [3
      13C]alanine/[3-13C]lactate ratio in ischemic, intact hearts (glucose = 0.24 +/-
      0.07 versus glucose+INO = 0.60 +/- 0.09; pyruvate = 0.49 +/- 0.08 versus
      pyruvate+INO = 0.89 +/- 0.08). At 7 minutes of ischemia, ATP content fell to 70
      +/- 3% with glucose+INO versus 58 +/- 5% with glucose alone. Rigor (stone heart)
      was delayed from 14.7 +/- 1.3 to 23.2 +/- 1.6 minutes with INO. INO did not
      change ATP content in ischemic hearts that were supplied pyruvate but delayed
      rigor (pyruvate = 9.9 +/- 1.2 minutes; pyruvate+INO = 15.6 +/- 1.0 minutes),
      possibly at the expense of glycogen. Supplemental glucose improved the
      effectiveness of INO with pyruvate to preserve ATP (pyruvate+glucose = 42 +/- 6%;
      pyruvate+glucose+INO = 72 +/- 6%) and further delayed rigor (pyruvate+glucose =
      13.3 +/- 1.5 minutes; pyruvate+glucose+INO = 20.3 +/- 1.8 minutes). Glucose
      metabolism supported improved energetic and contractile states in ischemic hearts
      treated with INO. Thus, cardioprotection of the ischemic heart by INO was
      associated with preservation of functional integrity and improved energy
      production due to increased glycolytic activity. Activation of glycolysis in the
      presence of INO was accommodated by augmented alanine production without the
      additional accumulation of lactate.

PMID- 1991357
TI  - Sarcomere dynamics in cat cardiac trabeculae.
AB  - The purpose of the present study was to describe sarcomere dynamics in thin
      trabeculae that were dissected from the right ventricle of kittens. The muscles
      were mounted in an experimental chamber and perfused with a modified Krebs
      Henseleit solution (25 degrees C). Sarcomere length (SL) was measured by laser
      diffraction techniques; force, by a silicon strain gauge; and velocity of
      sarcomere shortening, by the "isovelocity release" technique. Contractile
      activation was varied by changing the calcium concentration in the bathing medium
      ([Ca2+]o). Slack SL was 1.85 +/- 0.04 microns. When length of the muscle was held
      constant, the sarcomeres in the central region of the muscle shortened during the
      twitch by up to 21%. Both peak sarcomere isometric twitch force and unloaded
      velocity of sarcomere shortening (Vo) were a sigmoidal function of [Ca2+]o.
      Maximum Vo was 9.8 +/- 0.2 microns/sec; maximum sarcomere isometric twitch force
      was 108 +/- 13.8 mN/mm2. The shape of the force-SL relation was a function of
      [Ca2+]o. At [Ca2+]o = 1.5 mM, the force-SL relation was curved with its convexity
      toward the abscissa; at [Ca2+]o = 6 mM, the relation was curved with its
      convexity toward the ordinate. Vo depended in a linear manner on SL up to 2.2
      microns at [Ca2+]o = 1.5 mM. At [Ca2+]o = 6.0 mM, Vo depended also linearly on SL
      below 1.85 microns but became nearly independent of SL above 1.85 microns. Vo
      rose exponentially with time into the twitch up to 200 msec and remained constant
      thereafter at least up to 300 msec. Force, on the other hand, peaked at about 300
      msec. These results are comparable with those found in rat myocardium, although
      cat myocardium is less sensitive to [Ca2+]o and twitch kinetics are significantly
      slower than those in rat myocardium.

PMID- 1991358
TI  - Intracellular Na+ activity and positive inotropic effect of sulmazole in guinea
      pig ventricular myocardium. Comparison with a cardioactive steroid.
AB  - Recent studies suggest that inhibition of Na+,K(+)-ATPase may contribute to the
      positive inotropic action of the imidazopyridine sulmazole. Therefore, we
      investigated the effect of sulmazole and its stereoisomers and for comparison the
      effect of the cardioactive steroid dihydroouabain (DHO) on intracellular Na+
      activity by means of Na(+)-sensitive microelectrodes. In the resting papillary
      muscle of the guinea pig, (+/-)-sulmazole increased intracellular Na+ activity
      (aiNa) within 15-20 minutes by 0.5 +/- 0.1 (n = 3), 1.3 +/- 0.1 (n = 7), 2.7 +/-
      0.2 (n = 6), and 4.9 +/- 0.5 (n = 6) mM at 60, 100, 300, and 1,000 microM,
      respectively. (+)-Sulmazole was more effective than the racemate; aiNa was
      increased by 1.2 +/- 0.3, 2.1 +/- 0.3, and 4.0 +/- 0.2 mM at 60, 100, and 300
      microM, respectively (n = 2 for each concentration). In the contracting papillary
      muscle (0.2 Hz), (+)- and (+/-)-sulmazole (600 and 1,000 microM) produced a
      maximum positive inotropic effect that exceeded that of DHO by 11% and 8%,
      respectively. As an inotropic agent, (+)-sulmazole was almost twice as potent as
      the racemate. The maximum direct inotropic effect of (-)-sulmazole (1,000 microM)
      amounted to only 14% of the DHO maximum and was, in contrast to the racemate and
      (+)-sulmazole, antagonized by 3 microM carbachol. (-)-Sulmazole did not affect
      aiNa.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1991359
TI  - Myocardial sulfhydryl pool alterations occur during reperfusion after brief and
      prolonged myocardial ischemia in vivo.
AB  - Myocardial sulfhydryl (SH)-containing compounds, including reduced glutathione
      (GSH), are both defenses against and potential markers of reactive oxygen
      metabolite injury during ischemia and reperfusion. We examined the alterations in
      GSH and other myocardial SH pools during reperfusion in anesthetized dogs exposed
      to brief (15 minutes, n = 7) or prolonged (90 minutes, n = 6) regional ischemia
      caused by occlusion of the left anterior descending artery. Ninety minutes of
      ischemia followed by 5 hours of reperfusion, which resulted in myocardial
      necrosis of 43.9 +/- 4.0% of the area at risk, caused a 22% reduction in total
      myocardial SH groups (p less than 0.01), a 57% decrease in nonprotein myocardial
      SH groups (p less than 0.01), a 56% decrease in GSH (p less than 0.01), and a 62%
      decrease in non-GSH, nonprotein SH groups (p less than 0.02). However, protein SH
      groups were not significantly reduced (12% decrease, p = NS). Also, myocardial
      release of GSH and oxidized glutathione (GSSG) into the coronary venous effluent
      occurred during early reperfusion. In contrast, 15 minutes of ischemia, followed
      by 30 minutes of reperfusion, did not alter myocardial total SH groups, protein
      SH groups, or GSH (9% decrease, p = NS); nor was there reperfusion release of GSH
      or GSSG. However, even with brief ischemia, nonprotein SH groups decreased 23% (p
      less than 0.05), due mainly to a 59% decrease in the non-GSH, nonprotein SH pool
      (p less than 0.05). These changes after brief ischemia occurred without
      alterations in myocardial GSSG or the GSH/GSSG ratio.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1991360
TI  - Types of baroreceptor afferent neurons.

PMID- 1991361
TI  - Prognostic value of thallium-201 myocardial perfusion imaging. A diagnostic tool
      comes of age.

PMID- 1991362
TI  - Vascular smooth muscle. A review of the molecular basis of contractility.

PMID- 1991363
TI  - Modulation of coronary vasomotor tone in humans. Progressive endothelial
      dysfunction with different early stages of coronary atherosclerosis.
AB  - The endothelium plays a critical role in the control of vasomotor tone by the
      release of vasoactive substances. Because endothelial injury or dysfunction is
      considered important very early in atherogenesis, we hypothesized that abnormal
      endothelial function precedes the angiographic detection of coronary
      atherosclerosis in the human coronary circulation. The coronary vasomotor
      responses to three different endothelium-mediated stimuli (intracoronary infusion
      of acetylcholine 10(-8) to 10(-6) M, increase in blood flow to induce flow
      dependent dilation, and sympathetic stimulation by cold pressor testing) were
      assessed by quantitative angiography and subselective intracoronary Doppler flow
      velocity measurements within the left anterior descending coronary artery in 38
      patients. All three stimuli elicited epicardial artery dilation in all 11
      patients with smooth coronary arteries and absence of risk factors for coronary
      artery disease (group 1). All nine patients with smooth coronary arteries but
      with hypercholesterolemia (group 2) demonstrated a selective impairment in
      endothelial function with vasoconstriction (35 +/- 12.7% decrease in mean luminal
      area) in response to acetylcholine but showed a preserved flow-dependent dilation
      (15.5 +/- 4.4% increase in mean luminal area) and vasodilation in response to
      cold pressor testing (14.2 +/- 4.6% increase in mean luminal area). In all nine
      patients with an angiographically defined smooth coronary artery segment but with
      evidence of atherosclerosis elsewhere in the coronary system (group 3), both
      acetylcholine and cold pressor testing induced vasoconstriction (26.2 +/- 8.7%
      and 18.7 +/- 7.9% decrease in mean luminal area, respectively), whereas flow
      dependent dilation was preserved (20.4 +/- 8.7% increase in mean luminal area).
      In the nine patients with angiographic evidence of wall irregularities (group 4),
      flow-dependent dilation was also abolished and vasoconstriction occurred in
      response to acetylcholine and cold pressor testing (34.5 +/- 10.7% and 19.9 +/-
      6.3% decrease in mean luminal area, respectively). All coronary artery segments
      dilated in response to nitroglycerin, suggesting preserved function of vascular
      smooth muscle. Despite similar reductions in coronary vascular resistance in
      response to the smooth muscle relaxant papaverin, patients with
      hypercholesterolemia demonstrated a selective impairment of vasodilation of the
      resistance vasculature in response to acetylcholine (p less than 0.05 versus
      groups 1, 3, and 4). Thus, there is a progressive impairment of endothelial
      vasoactive functioning in coronary arteries of patients with different early
      stages of atherosclerosis, beginning with a selective endothelial dysfunction in
      angiographically defined normal arteries in patients with hypercholesterolemia
      and progressively worsening to a complete loss of endothelium-mediated
      vasodilation in angiographically defined atherosclerotic coronary
      arteries.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1991364
TI  - Endothelium-dependent responses in long-term human coronary artery bypass grafts.
AB  - In the present study, responses of long-term human coronary artery bypass grafts
      (CABGs) to known endothelium-dependent vasodilators, acetylcholine, calcium
      ionophore A23187, thrombin, and histamine, as well as authentic nitric oxide, the
      putative endothelium-derived relaxing factor, were studied. Sixteen CAGBs were
      isolated within 1-2 hours from hearts of 14 patients receiving a cardiac
      transplant. A total of 109 ring segments were prepared from these CABGs and
      studied in vitro. The duration of the CABGs ranged from 7 months to 12 years.
      Addition of acetylcholine (0.01-10 microM), calcium ionophore A23187 (0.01-1.0
      microM), thrombin (0.01-1.0 unit/ml), and histamine (0.01-1.0 microM)
      consistently produced a dose- and endothelium-dependent relaxation, reaching a
      maximum of -35.3 +/- 3.3%, -45.3 +/- 5.5%, -26.9 +/- 4.8%, and -17.8 +/- 2.5%
      (mean +/- SEM), respectively. No significant difference was observed among the
      CABGs with different duration of transplantation, whereas the relaxant responses
      of different segments along the entire length of a CABG were markedly different.
      These latter differences in the endothelium-dependent responses appear to
      correlate inversely with the development of intimal proliferative lesions in
      these CABGs. Addition of nitric oxide (0.01-10 microM) produced a potent dose-
      and endothelium-independent relaxation, which was also slightly depressed in
      CABGs with severe intimal proliferation. These results demonstrate that long-term
      transplanted human saphenous vein grafts retain their endothelium-dependent
      responses and that development of severe intimal proliferative lesions, rather
      than the duration of the grafts, result in marked alterations in the reactivity
      of these transplanted CABGs.

PMID- 1991365
TI  - Accuracy of exercise electrocardiography in detecting physiologically significant
      coronary arterial lesions.
AB  - The accuracy of exercise electrocardiography in detecting a physiologically
      significant coronary artery stenosis has been assessed previously by comparing
      the exercise test with a coronary arteriogram. The inherent inaccuracy of
      visually determined percent diameter stenosis measurements might have lead to the
      conclusion that the exercise electrocardiogram was less accurate than it truly
      was. To determine the accuracy of the exercise electrocardiography in detecting a
      physiologically significant coronary stenosis, we studied 40 patients with one
      vessel, one-lesion coronary artery disease, a normal resting electrocardiogram,
      and no hypertrophy or prior infarction. Each patient underwent exercise
      electrocardiography (Bruce protocol) that was interpreted as abnormal if the ST
      segment developed 0.1-mV or greater depression 80 msec after the J point. The
      physiological significance of each coronary stenosis was assessed by measuring of
      coronary flow reserve (peak divided by resting blood flow velocity) in the
      stenotic artery using a Doppler catheter and intracoronary papaverine (normal,
      3.5 or greater peak/resting velocity). The percent diameter and percent area
      stenosis produced by each lesion were determined using quantitative angiography
      (Brown/Dodge method). Of the 17 patients with reduced coronary flow reserve (3.5
      or greater peak/resting blood flow velocity) in the stenotic artery, 14 had an
      abnormal exercise electrocardiogram (sensitivity, 0.82; 95% confidence interval,
      0.70-0.94). Conversely, 20 of 23 patients with normal coronary flow reserves had
      normal exercise tests (specificity, 0.87; 95% confidence interval, 0.77-0.97).
      The exercise electrocardiogram was abnormal in each of 11 patients with markedly
      reduced coronary flow reserve (less than 2.5 peak/resting velocity) and in three
      of six patients with moderately reduced reserve (2.5-3.4 peak/resting velocity).
      The products of systolic blood pressure and heart rate at peak exercise were
      significantly correlated with coronary reserve in patients with truly abnormal
      exercise tests. In comparison, the sensitivity (0.61; 95% confidence interval,
      0.46-0.76) and specificity (0.73; 95% confidence interval, 0.60-0.86) of exercise
      electrocardiography in detecting a 60% or greater diameter stenosis may be
      significantly lower (p less than 0.05). Exercise electrocardiography, therefore,
      was a good predictor of the physiological significance (assessed by coronary flow
      reserve) of a coronary stenosis in patients with a normal resting
      electrocardiogram and no hypertrophy or prior infarction. Its value in a broader
      and larger patient population will require further study. These results, however,
      underscore the importance of a physiological gold standard in assessing the
      accuracy of noninvasive studies for detecting coronary artery disease.

PMID- 1991366
TI  - Effects of colestipol-niacin therapy on human femoral atherosclerosis.
AB  - The 2-year therapy effect on femoral atherosclerosis was evaluated in the
      Cholesterol Lowering Atherosclerosis Study (CLAS), a randomized, placebo-plus
      diet-controlled angiographic trial of colestipol-niacin therapy plus diet in men
      with previous coronary bypass surgery. Different diet compositions were
      prescribed to enhance the differential in blood cholesterol responses between the
      two groups. The annual rate of change in computer-estimated atherosclerosis
      (CEA), a measure of lumen abnormality, was evaluated between treatment groups. A
      significant per-segment therapy effect was found in segments with moderately
      severe atherosclerosis (p less than 0.04) and in proximal segments (p less than
      0.02). When segmental CEA measures were combined into a per-patient score using
      an adaptation of the National Heart, Lung, and Blood Institute scoring procedure,
      a significant therapy effect was observed (p less than 0.02). Total variance of
      the annual change rate in CEA was as predicted from pilot studies, but
      measurement variation was larger. The therapy effect observed in femoral
      arteries, although significant, was less marked than the strong and consistent
      benefit previously reported for both native coronary arteries and aortocoronary
      bypass grafts.

PMID- 1991367
TI  - In-hospital and 1-year mortality in 1,524 women after myocardial infarction.
      Comparison with 4,315 men.
AB  - We determined in-hospital and 1-year prognoses after acute myocardial infarction
      (MI) in 5,839 consecutive patients derived from 14 of 21 coronary care units in
      Israel during 1981-1983. Age-adjusted in-hospital mortality was 23.1% in 1,524
      women and 15.7% in 4,315 men (p less than 0.0005). One-year age-adjusted
      mortality rates in patients surviving hospitalization were 11.8% in women and
      9.3% in men (p = 0.03). Cumulative age-adjusted 1-year mortality rates were 31.8%
      in women and 23.1% in men (p less than 0.0005). Relative odds of mortality,
      covariate-adjusted for major prognostic factors that included age, prior MI,
      congestive heart failure, and infarct location by electrocardiogram, indicated
      that female gender was independently and significantly associated with increased
      mortality both during hospitalization (relative odds, 1.72; 95% confidence
      interval, 1.45-2.04) and at 1 year after discharge (relative odds, 1.32; 95%
      confidence interval, 1.05-1.66). In separate multivariate analyses for each
      gender, a major factor that emerged as a predictor of outcome in women, but not
      in men, was a reported history of diabetes mellitus, both for in-hospital
      mortality and for 1-year mortality. However, even in the nondiabetics in this
      population, female gender was a significant, independent predictor of in-hospital
      mortality. The findings of the present study substantiate that women fare worse
      than men after suffering an acute MI, that increased age does not fully account
      for the increased mortality in women, and that diabetic women are at particularly
      high risk once MI has occurred.

PMID- 1991368
TI  - Secular trends in Q wave and non-Q wave acute myocardial infarction. The
      Minnesota Heart Survey.
AB  - The Minnesota Heart Survey examined trends of Q wave and non-Q wave acute
      myocardial infarction (AMI) using a 50% random sample of all hospital discharges
      of patients with AMI or another acute coronary disease from 35 of 36 hospitals in
      1970 and 30 of 31 hospitals in 1980 in the Minneapolis-St. Paul metropolitan
      area. A total of 1,901 and 1,864 potential AMI cases were abstracted in 1970 and
      1980, respectively. Electrocardiograms were coded according to the Minnesota
      code. AMIs were validated by computerized algorithm based on chest pain, enzymes,
      electrocardiograms, and autopsy. This study shows that with the use of a
      consistent, standard diagnostic algorithm, attack rates for Q wave AMI did not
      change significantly between 1970 and 1980 and that attack rates for non-Q wave
      AMI decreased significantly during the same decade. However, when the more
      sensitive cardiac enzymes creatine phosphokinase and creatine phosphokinase-MB
      were considered, attack rates of both Q wave and non-Q wave AMIs increased. This
      research documents four important trends for community AMI rates that are at
      variance with those reported by others. There was a decline in non-Q wave AMI
      attack rates from 1970 to 1980; women had outcomes equal to or worse than those
      for men for both case-fatality and 7-year survival rates; patients with non-Q
      wave AMIs had worse in-hospital prognoses than those with Q wave AMIs; and 7-year
      survival rates were worse for Q wave AMI in 1980. These findings demonstrate the
      need for standard diagnostic criteria for Q wave and non-Q wave AMI if trends are
      to be monitored. In the future, as new trials of operative and nonoperative
      therapies of AMI are undertaken, these considerations will increase in
      importance.

PMID- 1991369
TI  - Impairment of the myocardial ultrastructure and changes of the cytoskeleton in
      dilated cardiomyopathy.
AB  - This study was designed to determine the morphological correlate of chronic heart
      failure. Myocardial tissue from eight patients undergoing transplantation surgery
      because of end-stage dilated cardiomyopathy was investigated by electron
      microscopy and immunocytochemistry using monoclonal antibodies against elements
      of the cytoskeleton: desmin, tubulin, vinculin, and vimentin. The tissue showed
      hypertrophy, atrophy of myocytes, and an increased amount of fibrosis.
      Ultrastructural changes consisted of enlargement and varying shape of nuclei,
      numerous very small mitochondria, proliferation of T tubules, and accumulation of
      lipid droplets and glycogen. The most obvious ultrastructural alteration was the
      decrease of myofilaments, ranging from rarefication to complete absence of
      sarcomeres in cells filled with unspecified cytoplasm. Immunocytochemistry showed
      that desmin was localized at the Z lines. In diseased myocardium, the amount of
      desmin was increased, but it was disorderly arranged. Tubulin formed a fine
      network throughout the myocytes and was significantly increased in
      cardiomyopathic hearts. Vinculin, a protein closely associated with the
      cytoskeleton, occurred not only at the sarcolemma and the intercalated disc but
      also within the myocardial cells. Ultrastructural changes and alterations of the
      cytoskeleton were severe in about one third of all cells. About one third of all
      cells showed moderately severe changes, and the remaining cells were normal.
      Vimentin was present in the interstitial cells and was increased in relation to
      the increase of fibrosis. We conclude that the increase of fibrosis, the
      degeneration of hypertrophied myocardial cells, and the alterations of the
      cytoskeleton are the morphological correlates of reduced myocardial function in
      chronic heart failure.

PMID- 1991370
TI  - Acute hemodynamic effects of captopril in children with a congestive or
      restrictive cardiomyopathy.
AB  - The acute hemodynamic effects of captopril were evaluated at cardiac
      catheterization in 16 children (age, 0.3-18 years) with cardiomyopathy. Twelve
      children had congestive cardiomyopathy, whereas four had restrictive
      cardiomyopathy. Hemodynamic measurements were obtained 30 and 60 minutes after
      the oral administration of captopril (0.5 mg/kg). Blood pressures were measured
      in the aorta, pulmonary artery, right atrium, and pulmonary capillary wedge
      position; cardiac outputs were measured by the thermodilution technique.
      Hemodynamic data could not be obtained after the administration of captopril in
      one child with congestive cardiomyopathy because of an immediate, severe
      hypotensive response. In 11 of 12 children with congestive cardiomyopathy,
      cardiac index increased by 22%, from 2.3 to 2.8 l/min/m2 (p less than 0.05), and
      stroke volume increased by 22%, from 23 to 28 ml/m2 (p less than 0.05). Systemic
      vascular resistance decreased from 32 to 21 units.m2 (p less than 0.01), but the
      mean aortic pressure did not change significantly. In contrast, four children
      with restrictive cardiomyopathy had no change in cardiac output after captopril,
      but there was a trend toward significant arterial hypotension (mean aortic
      pressure decreased from 78 to 59 mm Hg). Thus, captopril acutely reduced systemic
      vascular resistance and increased both cardiac output and stroke volume in
      children with congestive cardiomyopathy. In children with restrictive
      cardiomyopathy, however, captopril did not affect cardiac output, but it did
      decrease aortic pressure. These data indicate that captopril may benefit children
      with a congestive cardiomyopathy but that captopril probably should not be used
      in children with restrictive disease.

PMID- 1991371
TI  - What is the best method for assessing the long-term outcome of surgery for
      accessory pathways and atrioventricular junctional reentrant tachycardias?
AB  - The success of surgery for supraventricular tachycardia (SVT) is evaluated by a
      variety of methods in different hospitals. Unfortunately, the predictive values
      of these methods are not known. We therefore compared the various methods in 261
      patients undergoing surgery for SVT at Westmead Hospital since 1981. Surgical
      outcome was assessed by early tests during the first week after surgery (serial
      12-lead electrocardiograms, telemetric monitoring of the electrocardiogram, and
      electrophysiological study performed using epicardial wires); later tests at 6
      months after surgery (12-lead electrocardiograms and electrophysiological study);
      and symptomatic review done by telephone interview at a median of 34 months after
      surgery. Early tests were obtained in 97%, later tests were obtained in 76%, and
      symptomatic review was obtained in 98% of patients. All of the examined tests
      were inaccurate methods of surgical assessment compared with the late
      electrophysiological study. A large proportion of the patients proven to be
      surgical failures at the late electrophysiological study were not detected by
      early tests (83%), by later electrocardiograms (66%), or by symptomatic
      assessment (41%). Accurate assessment of surgical outcome requires a late
      electrophysiological study to permit comparison of surgical techniques. Late
      electrophysiological study also provides accurate information on the current
      risks and benefits of proposed surgery for communication to patients to enable
      them to make an informed decision on future treatment. Most patients are willing
      to have a late electrophysiological study and usually benefit from clarification
      of their true surgical outcome.

PMID- 1991372
TI  - Intravital detection of skin capillary aneurysms by videomicroscopy with
      indocyanine green in patients with progressive systemic sclerosis and related
      disorders.
AB  - Conventional capillaroscopy and infrared fluorescence videomicroscopy with
      indocyanine green were performed at the nailfold in 12 healthy controls and 38
      patients with microangiopathy due to systemic sclerosis or related disorders.
      Saccular aneurysms featuring head and neck (type 1) and aneurysmatic enlargements
      (type 2) were defined. Microaneurysms were located at the apex or near the apex
      of capillary loops and were significantly more common in patients than in
      controls (p less than 0.02 for type 1 and p less than 0.001 for type 2).
      Combination of the two lesions was found only in patients and appears to be a
      valuable new diagnostic sign for the presence of microangiopathy. In comparison
      with conventional capillaroscopy, about twice as many microaneurysms were
      detected by videomicroscopy with indocyanine green coupling almost completely to
      plasma proteins. The new technique allows visualization of capillary aneurysms
      even when filled only by plasma.

PMID- 1991373
TI  - Effect of weight reduction in moderately overweight patients on recorded
      ambulatory blood pressure and free cytosolic platelet calcium.
AB  - Although platelet cytosolic calcium has been shown to decrease during
      pharmacological treatment of hypertension, there is no evidence that cytosolic
      calcium also falls during a nonpharmacological reduction in blood pressure. To
      provide such evidence, we examined prospectively the relation between platelet
      cytosolic calcium and ambulatory blood pressure during weight reduction in
      moderately overweight (body mass index [BMI] greater than 25), mildly
      hypertensive individuals. The experimental group (responders: BMI reduction
      greater than 5%) consisted of 19 patients who lost 8.5 +/- 2.9 kg (mean +/- SD, p
      less than 0.05) during a 10-week hypocaloric diet, whereas the control group
      (nonresponders: BMI reduction less than 5%) consisted of 12 patients who showed
      no relevant change in body weight (-2.0 +/- 1.3 kg) during the same period of
      time. The moderate weight loss of the responders decreased blood pressure by 14/5
      mm Hg (p less than 0.05), as measured by ambulatory monitoring, which renders a
      placebo effect unlikely. This nonpharmacological reduction in blood pressure was
      accompanied by a proportional 11% decrease (p less than 0.05) in platelet
      cytosolic calcium and also by significant (p less than 0.05) decreases in plasma
      catecholamines and serum cholesterol. These findings establish the concept of a
      nonpharmacological reduction in free cytosolic platelet calcium in humans and add
      further evidence suggesting a link between intracellular calcium homeostasis and
      blood pressure regulation.

PMID- 1991374
TI  - Relation between leisure-time physical activity and blood pressure in older
      women.
AB  - Although there is some evidence that physical activity may decrease blood
      pressure in young and middle-aged women, the physical activity-blood pressure
      association in older women has rarely been studied. As part of an ongoing
      community-based study of chronic disease, 641 Caucasian women between the ages of
      50 and 89 years had blood pressure measured following the Hypertension Detection
      and Follow-up Program protocol. They also answered selected Health Interview
      Survey questions about their leisure-time activity and were classified into
      categories of light (58%), moderate (24%), heavy (6%), or no physical activity
      (12%) by the estimated metabolic rate required for each activity. Women who
      engaged in any physical activity were significantly younger and thinner than
      sedentary women and had lower fasting and 2-hour postchallenge insulin levels.
      They did not differ in alcohol consumption, cigarette use, or prevalence of
      coronary heart disease or diabetes. Rates of systolic and diastolic hypertension
      were significantly lower in women participating in light, moderate, or heavy
      physical activity compared with sedentary women. Blood pressure levels decreased
      with each increase in reported activity intensity (p less than 0.005 for trend),
      with systolic blood pressure approximately 20 mm Hg lower in the heaviest
      activity group compared with systolic blood pressure in sedentary women.
      Intergroup differences remained statistically significant after adjustment for
      age and body mass index. Although physical activity was associated with lower
      fasting and 2-hour postchallenge insulin levels (p less than 0.01 for trend),
      adjustment for insulin levels did not alter blood pressure differences among
      activity groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1991375
TI  - Mechanisms of reoxygenation injury in cultured ventricular myocytes.
AB  - To investigate factors contributing to reperfusion and reoxygenation myocardial
      injury, we exposed layers of cultured chick ventricular myocytes to severe
      hypoxia for up to 3 hours in the presence of 20 mM 2-deoxyglucose, zero glucose,
      and 5 mM pyruvate, and then exposed the myocytes to reoxygenation. Lactate
      dehydrogenase (LDH) release was moderately increased during 3 hours of hypoxia
      but was increased markedly during reoxygenation. Coincident changes in
      intracellular calcium concentration ([Ca2+]i) and cell motion were also measured
      during hypoxia and reoxygenation. During hypoxia, [Ca2+]i increased to more than
      1 microM, and with reoxygenation, [Ca2+]i abruptly decreased slightly but
      remained elevated more than 1 microM. Cells developed a stable rigor after 30
      minutes of hypoxia. Reoxygenation caused a marked hypercontracture within 5
      minutes. Pretreatment of myocytes with either 2,3-butanedione monoxime, which
      inhibits Ca2(+)-dependent force development, or cyanide inhibited reoxygenation
      hypercontracture. LDH release after reoxygenation was also significantly reduced
      in the presence of 2,3-butanedione monoxime. Treatment of myocytes with
      superoxide dismutase and catalase during hypoxia also resulted in a decrease in
      LDH release during reoxygenation. We conclude that an abrupt increase in [Ca2+]i
      during reoxygenation does not account for reoxygenation injury. However, in the
      presence of elevated [Ca2+]i, reoxygenation and the resulting probable
      resynthesis of ATP causes [Ca2+]i-dependent myofilament crossbridge cycling, and
      the resulting hypercontracture contributes to myocyte damage. The generation of
      oxygen free radicals after reoxygenation also appears to contribute to cell
      injury in this system.

PMID- 1991376
TI  - Mechanism of the effect of exogenous fructose 1,6-bisphosphate on myocardial
      energy metabolism.
AB  - The effects of fructose 1,6-bisphosphate (F-1,6-P2) on the isolated Langendorff
      perfused heart were studied by monitoring flavoprotein fluorescence, oxygen
      consumption (MVO2), coronary flow (Fc), systolic intraventricular pressure
      (Psys), diastolic intraventricular pressure, and contraction frequency. The
      cellular energy state and cytosolic pH were determined by means of 31P nuclear
      magnetic resonance. Infusion of 5 mM F-1,6-P2 caused a rapid shift toward
      reduction in the flavoprotein redox state and initial 50% and 44% decreases in
      Psys and MVO2, respectively. After a partial recovery, these measures remained
      11% and 25% below the basal value. Concomitantly, after an initial transient
      increase of 13%, Fc remained 17% lower than in the basal state. When the F-1,6-P2
      concentration was subsequently increased to 10 mM, psys and MVO2 dropped
      temporarily to 31% and 29% of the basal value and then remained at 50% and 53%,
      respectively. Simultaneously, a brief increase was observed in Fc, which then
      fell 34% below the basal value. Rapid reoxidation of the flavoproteins and
      increases in MVO2, Psys, and Fc occurred on discontinuation of the F-1,6-P2
      infusion. 31P nuclear magnetic resonance during infusions of both 5 and 10 mM F
      1,6-P2 revealed a decrease in cytosolic inorganic phosphate and a tendency to
      increase creatine phosphate, suggesting elevation in the cellular energy state.
      No changes in intracellular pH occurred as estimated from the chemical shift of
      the nuclear magnetic resonance of inorganic phosphate. F-1,6-P2 (5 mM and 10 mM)
      lowered the free Ca2+ concentration in the Krebs-Henseleit bicarbonate buffer (by
      32% and 47%, respectively). This probably explains the effects of F-1,6-P2 on
      mechanical work performance and cellular respiration. A direct metabolic effect
      also exists, however, because flavoprotein reduction by F-1,6-P2 could be
      observed in the K(+)-arrested heart, where its effects on MVO2 were minimal. This
      redox effect may not be caused by changes in free Ca2+ concentration because it
      could not be reproduced by infusion of EGTA.

PMID- 1991377
TI  - A new method for quantification of regurgitant flow rate using color Doppler flow
      imaging of the flow convergence region proximal to a discrete orifice. An in
      vitro study.
AB  - While color Doppler flow mapping has yielded a quick and relatively sensitive
      method for visualizing the turbulent jets generated in valvular insufficiency,
      quantification of the degree of valvular insufficiency has been limited by the
      dependence of visualization of turbulent jets on hemodynamic as well as
      instrument-related factors. Color Doppler flow imaging, however, does have the
      capability of reliably showing the spatial relations of laminar flows. An area
      where flow accelerates proximal to a regurgitant orifice is commonly visualized
      on the left ventricular side of a mitral regurgitant orifice, especially when
      imaging is performed with high gain and a low pulse repetition frequency. This
      area of flow convergence, where the flow stream narrows symmetrically, can be
      quantified because velocity and the flow cross-sectional area change in inverse
      proportion along streamlines centered at the orifice. In this study, a gravity
      driven constant-flow system with five sharp-edged diaphragm orifices (ranging
      from 2.9 to 12 mm in diameter) was imaged both parallel and perpendicular to the
      direction of flow through the orifice. Color Doppler flow images were produced by
      zero shifting so that the abrupt change in display color occurred at different
      velocities. This "aliasing boundary" with a known velocity and a measurable
      radial distance from the center of the orifice was used to determine an
      isovelocity hemisphere such that flow rate through the orifice was calculated as
      2 pi r2 x Vr, where r is the radial distance from the center of the orifice to
      the color change and Vr is the velocity at which the color change was noted.
      Using Vr values from 54 to 14 cm/sec obtained with a 3.75-MHz transducer and from
      75 to 18 cm/sec obtained with a 2.5-MHz transducer, we calculated flow rates and
      found them to correlate with measured flow rates (r = 0.94-0.99). The slope of
      the regression line was closest to unity when the lowest Vr and the
      correspondingly largest r were used in the calculation. The flow rates estimated
      from color Doppler flow imaging could also be used in conjunction with continuous
      wave Doppler measurements of the maximal velocity of flow through the orifice to
      calculate orifice areas (r = 0.75-0.96 correlation with measured areas).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1991378
TI  - Effects of pressure and volume of the receiving chamber on the spatial
      distribution of regurgitant jets as imaged by color Doppler flow mapping. An in
      vitro study.
AB  - Regurgitant jet dimensions imaged by color Doppler flow mapping have been used to
      evaluate the severity of valvular insufficiency in clinical studies. To study the
      effect of pressure and volume within the receiving chamber on the magnitude of
      spatial distribution of regurgitant jets assessed by color Doppler techniques, we
      designed a simple constant-flow model in which a jet was driven through a known
      orifice (1.5 mm2) into a compliant receiving chamber by a steady-flow pump. A
      distal tube at the outflow closed the system and maintained the volume of the
      chamber constant during pump operation. We varied flow rate from 60 to 270 ml/min
      into elastic balloons with different static compliances of 1, 2, 4.5, and 9 ml/mm
      Hg (pressures of 57, 28, 18, and 8 mm Hg, respectively); the balloons served as
      receiving chambers at the constant volume of 150 ml. We also evaluated the effect
      of different volumes of a receiving chamber (110, 130, and 150 ml and pressures
      of 5, 15, and 24 mm Hg) with a static compliance of 2 ml/mm Hg over the same
      range of flow rates. For each of the different balloons, jet area correlated
      linearly with the jet velocity across the orifice (r = 0.98, 0.99, 0.98, and
      0.97) and also with flow rate (r = 0.97, 0.99, 0.98, and 0.99). At the same flow
      rate and volume of receiving chamber, however, the jet area imaged by color
      Doppler decreased as the pressure in the receiving chamber increased, although
      receiving-chamber volume was constant.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1991379
TI  - Oral clofilium produces sustained lowering of defibrillation energy requirements
      in a canine model.
AB  - The effect of long-term oral administration of antiarrhythmic drugs on
      defibrillation energy requirements is not well understood. We examined the effect
      of clofilium, a drug that prolongs cardiac action potential duration without
      slowing cardiac conduction, on defibrillation energy requirements and ventricular
      effective refractory periods in a canine model during a 3-week period. Epicardial
      patch electrodes were implanted in 12 dogs, and baseline testing was conducted
      under fentanyl anesthesia on day 7. An oral clofilium (100 mg/day) regimen was
      started on day 8. Six clofilium-treated and six control dogs underwent repeated
      testing on days 14, 21, and 28 after surgery. Truncated trapezoidal shocks were
      given repeatedly at various stored energies in random order; delivered current
      and impedance were measured; and delivered energy was calculated. The energy and
      current for 50% success in defibrillation (E50 and I50, respectively) were
      determined. For control animals, E50 increased by a mean 34 +/- 78%, 60 +/- 83%,
      and 69 +/- 122% compared with baseline (day 7) on days 14, 21, and 28,
      respectively. In contrast, E50 in clofilium-treated dogs decreased by 39 +/- 62%,
      24 +/- 33%, and 32 +/- 15% on days 14, 21, and 28, respectively. Mean current
      requirements (I50) remained relatively stable compared with baseline in control
      animals (-7 +/- 39%, +25 +/- 36%, +40 +/- 75% on days 14, 21, and 28,
      respectively). After clofilium administration I50 decreased by 36 +/- 22%, 32 +/-
      17%, and 33 +/- 17% on days 14, 21, and 28, respectively.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1991380
TI  - Magnitude and time course of extracellular potassium inhomogeneities during acute
      ischemia in pigs. Effect of verapamil.
AB  - Prior studies have demonstrated the presence of inhomogeneities in myocardial
      [K+]e after serial 10-minute occlusions of the left anterior descending coronary
      artery in the pig, even within restricted locations of an ischemic zone. These
      inhomogeneities are thought to underlie the electrophysiological abnormalities
      responsible for lethal ventricular arrhythmias through reentrant and nonreentrant
      pathways, but a clear association has not been demonstrated. As a prerequisite to
      establishing this association, these studies were performed to establish
      measurement standards for [K+]e inhomogeneity, to quantify the magnitude and time
      course of these inhomogeneities, to determine whether the inhomogeneities are
      greater in the ischemic border where lethal ventricular arrhythmias are known to
      originate, and to assess the effect of a known antifibrillatory drug on [K+]e
      inhomogeneities. [K+]e (expressed as the change in potassium equilibrium
      potential, dEK [mV]) was measured in 15 preparations using an average of 17
      closely spaced, critically calibrated K(+)-sensitive electrodes having stable
      response characteristics. A series of four 10-minute occlusions each separated by
      a 50-minute reperfusion period were performed in each study. In half of the
      studies, intravenous verapamil (0.2 mg/kg bolus followed by 0.0065 mg/kg/hr) was
      administered before the fourth occlusion. In nine studies (five control and four
      verapamil), electrodes were placed in the marginal ischemic zone (from 2 mm
      outside to 5 mm inside the visible cyanotic border). In six other studies (three
      control and three verapamil), electrodes were placed in the central ischemic zone
      (10-20 mm within the ischemic region). We determined that the standard deviation
      is the best measure of inhomogeneity and that 12 equivalent measurement sites are
      required to estimate it with a satisfactory degree of statistical confidence. We
      found that after 10 minutes of ischemia, mean dEK was 1.6 times greater in the
      central than in the marginal ischemic zone, whereas mean standard deviation at
      the same time was 1.5 times greater in the marginal than in the central ischemic
      zone. Verapamil reduced mean dEK and mean standard deviation in both ischemic
      zones for most of the occlusion by delaying the rise in [K+]e and the
      inhomogeneity of that rise by 3-5 minutes. Comparisons of mean dEK with mean
      standard deviation revealed a steep linear relation in the marginal zone and a
      curvilinear relation in the central zone where higher mean dEK values were not
      accompanied by higher values for mean standard deviation. Furthermore, we
      determined that these relations were not altered by verapamil.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 1991381
TI  - Changes in left ventricular volume, mass, and function during the development and
      regression of supraventricular tachycardia-induced cardiomyopathy. Disparity
      between recovery of systolic versus diastolic function.
AB  - Chronic supraventricular tachycardia causes a dilated cardiomyopathy in man.
      Terminating this tachycardia appears to result in symptomatic improvement;
      however, its effects on left ventricular (LV) volume, mass, and function have not
      been fully examined. Accordingly, hemodynamic studies using simultaneous
      echocardiography and catheterization were performed in three groups of pigs: 1)
      those subjected to rapid left atrial pacing (240 beats/min) for 3 weeks (SVT, n =
      8), 2) those subjected to supraventricular tachycardia for 3 weeks followed by
      termination of pacing and a 4-week recovery period (PSVT, n = 9), and 3) sham
      operated controls (CTR, n = 10). Systolic pump function was assessed using
      fractional shortening (FS), peak ejection rate [peak (-)dD/dt], and maximum rate
      of pressure development [peak (+)dP/dt]. Diastolic function was assessed using
      the time constant of isovolumic pressure decline (tau), peak early diastolic
      filling rate [peak (+)dD/dt], the chamber stiffness constant (Kc), and the
      myocardial stiffness constant (Km). Supraventricular tachycardia caused LV
      dilation (end-diastolic dimension [EDD] increased from 3.5 +/- 0.4 cm in CTR to
      4.9 +/- 0.5 cm in SVT, p less than 0.05) but no change in LV mass (LV weight-to
      body weight ratio [LV/BW]) was 2.58 +/- 0.3 g/kg in CTR and 2.66 +/- 0.4 g/kg in
      SVT), all indexes of systolic function became abnormal (FS fell from 30 +/- 4% in
      CTR to 13 +/- 5% in SVT, p less than 0.05), and the indexes of relaxation and
      filling were slowed (tau increased from 36 +/- 3 msec in CTR to 51 +/- 13 msec in
      SVT, p less than 0.05). There were no significant changes in Kc or Km. After
      terminating the supraventricular tachycardia, LV volume fell but remained greater
      than that in CTR (EDD was 4.2 +/- 0.4 cm in PSVT, p less than 0.05 versus CTR)
      and substantial LV hypertrophy developed (LV/BW was 3.48 +/- 0.5 g/kg in PSVT, p
      less than 0.05 versus CTR). Systolic function returned to normal (FS was 31 +/-
      5% in PSVT) but diastolic function remained abnormal. In PSVT, tau remained
      prolonged (49 +/- 12 msec, p less than 0.05 versus CTR), Kc increased from 3.7 +/
      1.0 in CTR to 7.4 +/- 1.2 (p less than 0.05), and Km increased from 4.4 +/- 1.5
      in CTR to 13.9 +/- 9.7 (p less than 0.05). Thus, the improvement in systolic
      function that occurs after the termination of supraventricular tachycardia is
      associated with the development of LV hypertrophy and persistent diastolic
      dysfunction.

PMID- 1991382
TI  - Mechanisms contributing to increased synthesis of plasminogen activator inhibitor
      type 1 in endothelial cells by constituents of platelets and their implications
      for thrombolysis.
AB  - We recently hypothesized that after pharmacologically induced coronary
      thrombolysis, increased activity of plasminogen activator inhibitor type 1 (PAI
      1) retards recanalization, contributes to early reocclusion, or both. This
      hypothesis was based on the increased elaboration of PAI-1 that we observed in
      cultured liver cells exposed to growth factors releasable from platelets
      activated at sites of thrombosis in vivo. PAI-1 released locally is particularly
      likely to attenuate lysis of thrombi that are targets of thrombolytic drugs.
      Accordingly, the present study was performed to determine whether synthesis of
      PAI-1 by endothelial cells is augmented by products of platelets. Lysates from
      platelets (0.5-8.0 x 10(4)/mm3 media, i.e. less than 10% of the concentration of
      platelets in blood) increased synthesis and release of PAI-1 into both the
      extracellular matrix and conditioned media (by 2.8-fold and 3.3-fold within 6 and
      24 hours, respectively). Synthesis of neither tissue-type plasminogen activator
      nor overall protein increased. Increased synthesis of PAI-1 was confirmed by
      immunoprecipitation of [35S]PAI-1 after metabolic labeling of cells. The
      increased elaboration of PAI-1 was consistent with increased transcription as
      reflected by the observed increase in PAI-1 mRNA of 2.2-fold in 4 hours. Effects
      of platelet lysates were simulated by transforming growth factor beta (TGF-beta),
      known to be present in platelet alpha-granules and released with platelet
      activation. Antibody to TGF-beta reduced the stimulation of PAI-1 synthesis by
      TGF-beta, as expected, by 82%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1991383
TI  - Loss of endothelial pertussis toxin-sensitive G protein function in
      atherosclerotic porcine coronary arteries.
AB  - Pertussis toxin, an irreversible inhibitor of some G proteins, inhibits
      endothelium-dependent relaxations to certain agonists in porcine coronary
      arteries. In the present study, the effects of the toxin were examined on
      endothelium-dependent and -independent relaxations of hypercholesterolemic and
      atherosclerotic porcine coronary arteries to assess the functional state of the
      endothelial pertussis toxin-sensitive G protein. Male Yorkshire pigs were
      maintained on either a regular diet (control group, n = 7) or a 2% high
      cholesterol diet (cholesterol-fed group, n = 7) for 10 weeks. After the initial 2
      weeks of maintenance, animals in both groups underwent balloon catheter removal
      of the endothelium of the left anterior descending or left circumflex coronary
      arteries. Endothelium-dependent responses were examined in vitro after 10 weeks
      of maintenance; at this time, a full lining of endothelial cells in both left
      coronary arteries was confirmed histologically. In arteries with endothelium of
      the control group (normal responses), pertussis toxin significantly inhibited the
      endothelium-dependent relaxations to serotonin, UK14304 (a selective alpha 2
      adrenergic receptor agonist), and thrombin but not those to ADP, bradykinin, or
      the calcium ionophore A23187. In previously denuded arteries of the control group
      (effects of endothelial regeneration alone) or intact arteries of the cholesterol
      fed group (effects of hypercholesterolemia alone), the relaxations to serotonin,
      UK14304, and thrombin were impaired significantly; those relaxations were
      impaired further in previously denuded arteries of the cholesterol-fed group
      (effects of atherosclerosis). The inhibitory effects of pertussis toxin were
      significantly reduced after endothelial regeneration and in hypercholesterolemia
      and were almost absent in atherosclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1991384
TI  - Myocardial stunning and hibernation. The physiology behind the colloquialisms.

PMID- 1991385
TI  - Promises and pitfalls of new devices for coronary artery disease.

PMID- 1991386
TI  - Regression of femoral atherosclerosis.

PMID- 1991387
TI  - Idiopathic dilated cardiomyopathy. An immunologic, genetic, or infectious
      disease, or all of the above?

PMID- 1991388
TI  - Captopril in children with cardiomyopathy.

PMID- 1991389
TI  - Calcium overload and ischemic myocardial injury.

PMID- 1991390
TI  - Functional chiral asymmetry in the descending thoracic aorta.

PMID- 1991391
TI  - Handgrip and coronary flow reserve.

PMID- 1991392
TI  - Intra-arterial urokinase as the initial therapy for acutely ischemic lower limbs.
AB  - Acute ischemia of the lower limb remains a significant risk to both life and
      limb. Mortality rates of approximately 10-30% and amputation rates of the same
      magnitude in the survivors are repeatedly reported despite advances in medical
      and surgical techniques. Our experience, which utilized percutaneous intra
      arterial thrombolysis as the initial treatment in 72 instances (63 patients), has
      resulted in a markedly lower mortality rate of 1.6% and a lower amputation rate
      of 8.5% in the survivors. Careful categorization by clinical degree of ischemia
      indicates that 82% of the cases were either threatened or irreversible limb
      ischemia. The initial treatment with thrombolysis did not preclude subsequent
      prompt surgical treatment when necessary; in these cases, thrombolysis promoted
      improved surgical results (100%) when it was successful. It markedly reduced the
      need for urgent surgery, usually simplified the subsequent surgical approach,
      diminished the overall need for surgery, and often accomplished a successful
      outcome alone (31%). Significant bleeding was not noted during subsequent
      surgical procedures and was noted in only 2.8% of the cases. Confirmation of
      these results and further improvements in technique might justify the use of an
      initially high-dose urokinase transcatheter infusion regimen as the initial
      treatment of choice for acute lower-limb ischemia.

PMID- 1991393
TI  - The natural history of peripheral vascular disease. Implications for its
      management.
AB  - The durability and the eventual complication rate of endovascular therapy
      (percutaneous transluminal angioplasty, laser-assisted angioplasty, and
      atherectomy) are not yet entirely clear, especially with respect to the treatment
      of atherosclerotic lesions in the femoropopliteal or distal arterial segments.
      Therefore, the indications for its use have not been firmly established and must
      take into consideration the natural history of the occlusive disease itself.
      Although some type of procedural intervention clearly is warranted in the
      presence of ischemic rest pain or tissue necrosis, intermittent claudication is
      the only complaint in approximately 70% of patients who present with either
      aortoiliac or femoropopliteal involvement. Most nondiabetic patients experience
      substantial symptomatic improvement with a daily exercise program, and their long
      term risks for either abrupt deterioration (20-25%) or amputation (less than 10%)
      are relatively low. In comparison, the 5-year mortality rate ranges from 20-40%
      even in claudicants, and as many as 40% of those with clinical indications of
      associated coronary artery disease have been shown angiographically to be
      candidates for myocardial revascularization. These observations suggest that
      traditional indications for surgical treatment (truly disabling claudication
      and/or limb salvage) also should be applied to endovascular therapy until its
      success is confirmed beyond speculation, and that incidental coronary disease
      deserves particular attention in patients with lower extremity ischemia.

PMID- 1991394
TI  - Intra-arterial thrombolysis. A surgical view.

PMID- 1991395
TI  - Intravascular stents. General principles and status of lower-extremity arterial
      applications.
AB  - The two major types of intravascular stents are balloon expandable and self
      expanding. Many animal and, more recently, clinical studies have begun to
      delineate the real and potential roles of stents. Although the ideal
      intravascular stent does not exist, it is possible to identify characteristics of
      the hypothetical ideal stent. Iliac and femoropopliteal arterial applications of
      metallic stents are reviewed. Stents have proved useful in postangioplasty
      elastic recoil, in some cases of postangioplasty restenosis, and in angioplasty
      induced dissection. Their role in primary angioplasty procedures is still
      uncertain, although in iliac angioplasty the immediate hemodynamic effects of
      angioplasty plus stenting are superior to those of angioplasty alone. It is clear
      that metallic stents have not solved the problem of postangioplasty restenosis,
      as restenosis still occurs in a significant number of cases. This problem is
      particularly evident in the femoropopliteal stent procedures, in which
      angiographic restenosis (more than 50% single diameter stenosis) at 6 months
      after treatment has occurred in approximately 30% of cases. The existence of
      poststenting restenosis, which often involves the stented segment, underscores
      the need for better drug regimens in angioplasty and for better understanding of
      the intimal fibrocellular proliferative response of the vessel wall to injury.
      Although potentially very useful, biodegradable stents are still a dream whose
      realization will demand the development of better materials.

PMID- 1991396
TI  - Diagnosis and evaluation of renovascular hypertension. Indications for therapy.
AB  - Renovascular hypertension is caused by two distinct conditions with different
      causes, fibromuscular dysplasia and atheroma. Diagnosis of the former is both
      simpler and more rewarding, whereas atheromatous lesions of the renal artery may
      be secondary to essential hypertension. It is therefore important to establish
      existence of functional renal ischemia as well as an anatomical lesion. Universal
      screening of all hypertensive patients is not recommended because of the
      relatively low prevalence of the disease and insufficient accuracy of available
      screening tests. When renovascular hypertension is clinically suspected, an oral
      captopril test is the most reliable office screening test. After this, digital
      subtraction angiography with renal vein renins or captopril renography are
      appropriate steps. However, the latter procedure, while promising, requires
      further evaluation. Duplex scanning of the renal arteries also comes into this
      category. Arteriography is done last, so that if renal ischemia is indicated,
      angioplasty can be attempted at the same time as arteriography.

PMID- 1991397
TI  - Natural history and pathophysiology of brain infarction.

PMID- 1991398
TI  - Noninvasive evaluation of cerebral ischemia. Trends for the 1990s.
AB  - A number of diagnostic tools have been developed over the past decade that
      facilitate the noninvasive evaluation of cerebral ischemia. From duplex Doppler
      ultrasound to xenon computed tomography and magnetic resonance angiography, a
      greater trend toward combining both anatomic and function information is
      anticipated. The methodology, limitations, and current clinical applications of
      these three diverse techniques, with emphasis on xenon computed tomography and
      magnetic resonance angiography, are discussed. Both xenon computed tomography and
      magnetic resonance angiography can be performed on current systems with minimal
      hardware and software modifications. As a result, standard anatomic and
      structural imaging can be supplemented with diverse information such as
      quantitative brain perfusion without and with flow challenging as well as flow
      mapping and velocity imaging, which approximates conventional x-ray angiography.

PMID- 1991399
TI  - Optimum results of the surgical treatment of carotid territory ischemia.
AB  - Continuing controversy over the role of carotid endarterectomy in stroke
      prevention is based largely on reports in which high perioperative morbidity and
      mortality rates obviate possible long-term benefit from the procedure. The
      purpose of this review is to examine optimal results of carotid surgery in order
      to describe the potential for the procedure in stroke prevention. Optimal
      surgical results are compared with optimal medical results in the therapy of
      symptomatic patients and with optimal nonsurgical results in the therapy of
      asymptomatic patients. Factors common to series with excellent results, such as
      patient selection and operative technique, are examined, and problems such as
      recurrent carotid stenosis and coexisting coronary disease, which continue to
      plague even the best surgical series, are discussed.

PMID- 1991400
TI  - Morphological observations late (greater than 30 days) after clinically
      successful coronary balloon angioplasty.
AB  - This report describes clinical, morphological, and histological findings late
      (1.6-24.1 months [average, 8.2 months]) after clinically successful coronary
      balloon angioplasty in 20 necropsied patients with coronary angioplasty
      restenosis. Clinical evidence of restenosis occurred in 14 (70%) of patients,
      including six patients with sudden coronary death. Of the 20 patients, 14 (70%)
      had cardiac causes of death and six (30%) had noncardiac causes of death. Two
      major subgroups of histological findings were observed: 1) intimal proliferation
      (60%) and 2) atherosclerotic plaques only. Of the eight sites with
      atherosclerotic plaques only, six were eccentric lesions and two were concentric
      lesions. No morphological evidence of previous angioplasty injury (cracks,
      breaks, or tears) was observed in the eight patients with atherosclerotic plaques
      only. Proposed mechanisms for the development of intimal proliferation involve
      the reaction of smooth muscle cells and platelets, whereas elastic recoil of
      overstretched eccentric or concentric atherosclerotic lesions represents the most
      likely explanation for the findings in the latter subgroup. On the basis of these
      morphological findings at angioplasty restenosis sites, specific treatment
      strategies for coronary artery balloon angioplasty restenosis are proposed.

PMID- 1991401
TI  - Clinical and anatomical considerations for surgery in aortoiliac disease and
      results of surgical treatment.
AB  - A variety of surgical procedures are available for the treatment of occlusive
      disease involving the aorta and iliac arteries. Use of the most appropriate
      operation in each patient, determined principally by disease location and patient
      risk, can provide highly effective relief of disabling claudication or limb
      threatening ischemia with low morbidity and mortality rates. The excellent,
      durable results of current surgical practice should serve as the standard with
      which newer treatment modalities must be compared.

PMID- 1991402
TI  - Clinical and anatomic considerations for surgery in femoropopliteal disease and
      the results of surgery.
AB  - From 1980 to 1988 we performed 288 femoropopliteal bypass operations in 231
      patients at the Oregon Health Sciences University. The indication for the
      procedure was claudication in 31% and the relief of limb-threatening ischemia in
      64%. Operative mortality occurred after four of these operations (1.4%),
      including three deaths from myocardial infarction and one death from stroke. The
      femoropopliteal bypass patients were divided into groups for patency analysis,
      including those undergoing bypass surgery with a good quality greater saphenous
      vein versus alternate bypass conduits and patients undergoing primary limb bypass
      versus those undergoing repeat bypass after prior bypass failure. Our overall
      primary graft patency for all femoropopliteal grafts was 79% at 5 years. Patients
      undergoing bypass with a good quality greater saphenous vein had primary graft
      patency of 85% at 5 years. Patients undergoing bypass using a conduit other than
      greater saphenous vein had a 5-year patency of 73%. Patients undergoing repeat
      bypass after a prior failed bypass had a 5-year patency of 57%.

PMID- 1991403
TI  - Clinical and anatomic considerations for surgery in tibial disease and the
      results of surgery.
AB  - Bypass vein grafts to the infrapopliteal arteries now achieve a 5-year cumulative
      patency equivalent to that of vein grafts to the popliteal arteries. The
      technique of in situ vein grafting to the tibial arteries is described and the
      results are presented. The 5-year cumulative patency for such bypasses and the 5
      year limb salvage in the same patients have both been approximately 80%. These
      results coupled with those reported from other centers that have sizable
      experience in tibial artery reconstruction suggest that there has been real
      progress over the past decade in the salvage of lower extremities in patients
      with far advanced peripheral vascular disease through the use of autogenous
      venous bypass grafts.

PMID- 1991404
TI  - Hot-tip laser. Results and complications.
AB  - The hot tip laser system for atheroablation has been used since mid-1984 as a
      device for broadening the indications for and extending the applicability of
      angioplasty in the management of lower-extremity atherosclerosis. It has been a
      controversial device. Although the system demonstrates that it can occasionally
      be useful for the management of occlusive as opposed to stenotic disease of the
      infrainguinal arteries, a close examination of the published data fails to
      demonstrate a consistent improvement in either the primary success or long-term
      patency rates for thermal energy applied to atheroma for recanalization of the
      lower extremity arteries.

PMID- 1991405
TI  - Laser angioplasty. A vascular surgeon's view.

PMID- 1991406
TI  - Efficacy of thrombolysis in infrainguinal bypass grafts.
AB  - The initial outcome of a consecutive series of 43 intra-arterial urokinase
      infusions for thrombosed infrainguinal grafts in 37 patients was analyzed. There
      was an 88% (38/43) technical success rate (complete clot lysis) and a 74% (32/43)
      clinical success rate. Complications occurred in 10 patients (23%) and were
      related to bleeding in four patients (9%). Patient age, graft age, location,
      material, and the duration of occlusion did not significantly influence the
      initial outcome, although there was a trend toward a higher bleeding complication
      rate among grafts less than or equal to 1 month of age at the time of
      thrombolysis. A second group of 43 infrainguinal grafts successfully recanalized
      using regional infusions of thrombolytic agents were followed for long-term
      patency. This group included 32 grafts successfully treated with urokinase and 11
      grafts recanalized with streptokinase. By life-table analysis there was a 55.6% 1
      year patency, which fell to 42.4% at 4 years. Vein grafts had significantly (p =
      0.01) better long-term patency than prosthetic grafts (69.3% versus 28.6% at 30
      months). Grafts with flow-limiting lesions identified and corrected by
      angioplasty or surgery also had significantly (p = 0.01) better long-term patency
      than those without such lesions (79.0% versus 9.8% at 2 years). Based on the
      results of our study compared with a survey of long-term results following
      secondary surgical procedures for thrombosed infrainguinal grafts, thrombolysis
      can be recommended in several circumstances. Thrombolysis is indicated for
      thrombosed vein grafts or when thrombus is present in distal runoff vessels.
      Thrombosed prosthetic grafts should be replaced by autogenous vein grafts
      whenever possible.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1991407
TI  - HIV-related encephalitis presenting as convulsant disease.
AB  - Because of the growing incidence of neurological disorders in HIV-infected
      patients, an early detection of the disease seems to be of paramount importance,
      especially in asymptomatic subjects. By using electroencephalography coupled with
      computerized spectral analysis and "mapping" (EEG-CSA), paroxysmal sharp activity
      was detected in 26 patients belonging to different stages of HIV infection. Seven
      of them (27%) were also symptomatic, (table; see text) showing signs of
      convulsant disease. The presence of focal or generalized paroxysmal activity,
      often associated with seizures, might suggest an early localization of HIV in
      cortical structures.

PMID- 1991408
TI  - Circumscribed midline EEG activity in neurologically normal neonates.
AB  - Activity occurring predominantly at or circumscribed to the midline electrodes
      Fz, Cz and Pz was examined in 18 neurologically normal neonates of 27-42 weeks
      conceptional age (CA). Admixtures of delta and beta activity, which sometimes
      resembled delta brushes and rhythmical theta activity, of less than three seconds
      duration were seen during the suppressed portions of trace alternant or
      discontinue quiet sleep in 27-32 week CA neonates. Single sharp midline waves, or
      entrained 4-8 Hz midline activity of 3 seconds or less duration, were found in
      preterm neonates (33-36.5 weeks CA) only in quiet sleep, whereas these phenomena
      were also present in active sleep in term (38.5-42 weeks CA) infants. Midline
      alpha activity with a duration less than or equal to 3 seconds was found
      initially in quiet sleep in the 33-36.5 week CA infants and then exclusively in
      active sleep in the term infants. These data consolidate and refine the existing
      literature on normal neonatal midline activity through the identification of the
      temporal and topographical characteristics of a spectrum of normal activity in
      infants of 32 weeks CA and older.

PMID- 1991409
TI  - Some problems in the clinical use of topographic EEG analysis.
AB  - The correct clinical use of topographic EEG analysis is labor intensive, time
      consuming and does not bypass the problems involved in conventional EEG
      interpretations. The physician interpreting maps needs not only to be fully
      cognizant of all the aspects of clinical electroencephalography but also of the
      special issues inherent in this methodology. Certain problems that are specific
      to topographic EEG analysis and that can lead to wrong interpretations are
      presented.

PMID- 1991410
TI  - Electro-clinical correlations of positive and negative sharp waves on the
      temporal and central areas in premature infants.
AB  - The goal of this study on 199 premature infants (24-41 weeks CA) was to
      investigate the electro-clinical correlations of positive and negative sharp
      waves, comparing those from the temporal and central areas. Positive discharges
      were seen more often less than 30 weeks CA and the negative type greater than 30
      weeks. Patients without sharp waves rarely have seizures and those with paroxysms
      often do, dependent in part on the number of these discharges. When negative
      sharp waves are found on the frontal or occipital areas, where they uncommonly
      occur, the incidence of seizure almost doubles, compared to those on the central
      or temporal areas. Periventricular leukomalacia (PVL) was seen in less than one
      fourth of all patients, increasing to 32% with negative sharp waves, but nearly
      doubling the latter incidence with positive paroxysms, seen especially on the
      temporal, rather than central areas. Positive discharges were seen much more
      frequently with stage III-IV hemorrhage (Hg) than in stage I-II and these were
      mainly temporal, not central in location. Seizures and Hg were related only with
      grade III-IV, not with grade I-II Hg. Based on these data, positive sharp waves
      would predict in 69% of these infants the presence of at least one of the triad
      of seizures, intracerebral Hg or PVL, similar for the temporal and central
      locations. Follow-up studies showed that normal records at 30 weeks often changed
      to abnormal ones around 36 weeks. Finally, sensitivity data showed that for the
      positive sharp wave the highest values were for PVL, the lowest for seizures and
      midway for Hg, while the negative sharp waves show exactly the opposite, highest
      for seizures and lowest for PVL.

PMID- 1991411
TI  - Replication and extension of P50 findings in schizophrenia.
AB  - In a paired click "conditioning (S1), Testing (S2)" paradigm the amplitudes of
      responses to (S1) as well as the degree of attenuation of S2 as compared to S1
      (S2/S1) were studied in two schizophrenic groups. Thirteen
      undifferentiated/disorganized (US) and thirteen paranoid (PS) patients were
      compared to thirteen age and sex matched normal volunteers. The US patients had
      significantly lower (S1) response amplitudes (P less than 0.001), as well as
      degree of attenuation of the response to (S2) (P less than 0.001) than the other
      two groups. No significant differences were found between the PS and N groups.
      Our data replicates the prior finding of decreased attenuation of the amplitude
      of the P50 wave in a paired click paradigm in schizophrenia. In addition, we
      showed that this phenomenon is significant mainly in the
      disorganized/undifferentiated patients as compared to the paranoid
      schizophrenics.

PMID- 1991412
TI  - Limbic autonomic arousal: its physiological classification and review of the
      literature.
AB  - The object of this article is to present a novel physiological classification of
      Limbic-Autonomic (LA) arousal on the basis of human physiological data,
      specifically the oro-nasal breathing patterns in man. It is proposed that the
      multidimensional LA arousal can be classified into five grades: Grade I: Non
      nasal (NN) or oral breathing with bilateral nasal congestion, and nonactive
      behavior, Grade II: Left Nasal (LN) breathing and quiet behavior, Grade III:
      Right Nasal (RN) breathing and active behavior, Grade IV: Bilateral Nasal (BN)
      breathing and very active behavior, and Grade V: Oral and Bilateral Nasal (ON)
      breathing with maximal behavioral activation. The data from polygraphic
      electroencephalographic recordings from five healthy volunteers, before, during
      and after exercise are presented in support of this physiological classification
      of LA arousal. On the basis of Limbic-Autonomic asymmetry a novel concept of
      "Visceral Dominance" is also proposed.

PMID- 1991413
TI  - Management of febrile seizures: current concepts and recommendations for
      phenobarbital and the electroencephalogram.
AB  - Recent emphasis in the medical and lay press on phenobarbital-induced cognitive
      deficits and failure to obtain satisfactory compliance and benefit from long-term
      anticonvulsant therapy has fueled the controversy concerning current concepts of
      management of febrile seizures and prompted alternative recommendations. A survey
      of pediatricians in Central and Southern Illinois showed the mean number of
      febrile seizures treated in an office practice in a 12-month period was 7.56 +/-
      7.4, of which 20% were of the complex type. Complex febrile seizures, affecting
      an estimated 5000 children in Illinois, were treated with phenobarbital by 90% of
      respondents, and therapy was continued for an average of 2 years. The
      electroencephalogram (EEG) was used in determining the need for phenobarbital
      prophylactic therapy by 52% of respondents. An alternative approach to treatment
      is outlined in light of the questionable benefits and potential side effects of
      long-term phenobarbital. Parental education and counseling in the management of
      fever and convulsions and intermittent methods of prophylaxis are emphasized, and
      the more limited use and careful monitoring of phenobarbital therapy in selected
      high-risk patients is suggested. The value of the EEG in prognosis and prediction
      of epilepsy in children with febrile seizures deserves further study.

PMID- 1991414
TI  - [Open, noncomparative multicenter study of the efficacy and tolerance of a
      spiramycin-metronidazole combination used in infectious oral pathology].

PMID- 1991415
TI  - The effect of stool consistency on rectal and neorectal emptying.
AB  - Although stool consistency is considered to be an important component of
      anorectal continence, its effect on rectal emptying has never been quantitated.
      In 12 healthy volunteers and 12 patients after ileal pouch-anal anastomosis
      (IPAA) (46 +/- 5 months after the operation; mean +/- SEM), perfused anal
      manometry was performed; movements of the anorectal angle were quantitated
      scintigraphically; and rectal capacity and compliance were measured by air
      insufflation of an intrarectal balloon at three infusion rates. The efficiency of
      rectal evacuation of three consistencies (5 percent, liquid; 7.5 percent
      semisolid gel; 11.25 percent solid gel; w/w) of Tc99m labeled artificial stool
      (aluminum magnesium silicate gel) was quantitated by gamma camera imaging. No
      abnormalities of pelvic floor function were demonstrated in either controls or
      patients. The mean neorectal capacity and compliance of patients with IPAA did
      not differ from control, (capacity; IPAA: 215 +/- 22 ml vs. control; 245 +/- 29
      ml; compliance; IPAA: 5.5 +/- 0.7 ml/cm H2O vs. control; 6.6 +/- 0.7 ml/cm H2O; P
      greater than 0.05). In controls, the percentage of the 7.5 percent consistency
      evacuated (81 +/- 5 percent, mean +/- SEM) was significantly more than the
      percentage evacuation of either the 5 percent consistency (67 +/- 7 percent) or
      the 11.25 percent consistency (77 +/- 2 percent) (P less than 0.05). After IPAA,
      the mean overall percent evacuation of the three stool consistencies was
      significantly less than control (52 +/- 6 percent after IPAA; 75 +/- 5 percent
      control, P less than 0.05). However, there was no significant difference in
      neorectal emptying between the liquid, the semisolid gel and the solid gel (56 +/
      6, 55 +/- 6, 51 +/- 9 percent, respectively, P greater than 0.1). We concluded
      that in healthy subjects but not in patients after IPAA, stool consistency
      affected the efficiency of evacuation of enteric content.

PMID- 1991416
TI  - The role of sphincteroplasty for fecal incontinence reevaluated: a prospective
      physiologic and functional review.
AB  - Sixteen female patients (mean age 54.1 years; range 34-74 years) with a 9.8-year
      (range 1-25 years) history of incontinence to solid stool underwent overlapping
      sphincteroplasty with internal sphincter imbrication without fecal diversion. All
      patients were prospectively evaluated with preoperative anorectal manometry,
      electromyography, and pudendal nerve motor latency assessment, postoperative
      anorectal manometry, and preoperative and postoperative functional evaluation.
      Mean and maximal resting pressures increased from 30 mm Hg and 49 mm Hg
      preoperatively to 40 mm Hg and 57 mm Hg, respectively, postoperatively. Likewise,
      mean and maximal squeeze pressures increased from 27 mm Hg and 48 mm Hg
      preoperatively to 39 mm Hg and 73 mm Hg, respectively, postoperatively (P less
      than 0.01). Furthermore, anal canal high pressure zone length was increased by
      sphincteroplasty from a mean of 0.9 cm (range 0-3 cm) to a mean of 2.1 cm (range
      1-4 cm). These objective physiologic improvements correlated well with subjective
      functional improvement. Subjectively, functional outcome was rated by patients as
      excellent in 38 percent, good in 38 percent, fair in 19 percent, and poor in only
      5 percent of cases. Overlapping sphincteroplasty with internal sphincter
      imbrication improves both the anal sphincter physiologic profile and fecal
      continence.

PMID- 1991417
TI  - DNA ploidy pattern in rectal carcinoid tumors.
AB  - The nuclear DNA pattern of 22 rectal carcinoids was determined by cytophotometry
      of paraffin embedded tissues. The results were compared with clinical as well as
      histopathologic features of the tumor. Three of the carcinoids with synchronous
      or metachronous metastasis had aneuploid DNA pattern, whereas 19 tumors with no
      metastasis showed diploid DNA pattern. No other single clinical or pathologic
      feature of the tumor could predict more accurately the malignant potential and
      the subsequent course of the rectal carcinoid. It is concluded that DNA
      aneuploidy in rectal carcinoid tumors is not so rare as indicated by earlier
      studies and that it is a factor of significant prognostic value.

PMID- 1991418
TI  - Detection by CT during arterial portography of colorectal cancer metastases to
      liver.
AB  - A prospective evaluation of the accuracy of real-time ultrasonography (US),
      computed tomography (CT), infusion hepatic angiography (IHA), and computed
      tomography during arterial portography (CT-AP) was performed on 65 resected liver
      metastases of colorectal cancers. The total detection rate was 58.5 percent for
      US, 56.3 percent for CT, 55.4 percent for IHA, and 86.2 percent for CT-AP. The
      sensitivity of 29 lesions with diameters of smaller than 1 cm was 65.5 percent
      for CT-AP, CT found only two, and both US and IHA localized no more than three.
      The smallest lesions detectable by CT-AP were as small as 0.4 cm in diameter. CT
      AP proved most useful in detecting the liver metastases, and the use of this
      technique is recommended for preoperative planning of hepatectomy on patients
      with liver metastases.

PMID- 1991419
TI  - Rectopexy is an ineffective treatment for obstructed defecation.
AB  - The symptoms of obstructed defecation have been attributed to rectal
      intussusception, and thus rectopexy has been advocated in the surgical
      management. In this study, patients with obstructed defecation underwent
      manometry and proctography before and after rectopexy. Seventeen patients (16
      females and one male, mean age 51.6 years) were studied. Eleven underwent
      anterior and posterior fixation of the rectum and six had posterior fixation
      only. Preoperatively five patients demonstrated rectoanal intussusceptions.
      Fifteen had significant pelvic descent. No significant change in maximum resting
      pressure, maximum voluntary contraction, pelvic descent, or anorectal angle was
      seen postoperatively. In the initial follow-up, many patients had significant
      amelioration of symptoms. However, on longer follow-up (mean 30.8 months) only
      two had long-term improvement. The remainder had a poor clinical result in spite
      of complete resolution of rectal intussusception. Many reported a worsening of
      symptoms as reflected by an increase in tenesmus and stool frequency. In the two
      cases with a satisfactory result, both could empty the rectum completely and
      demonstrated rectoanal intussusception on preoperative evacuation proctography.
      In those with poor results, four had complete emptying and three had rectoanal
      intussusception. In conclusion rectopexy is an ineffective treatment for
      obstructive defecation in most patients.

PMID- 1991420
TI  - The reproducibility of measuring the anorectal angle in defecography.
AB  - Dynamic proctography is a radiographic procedure that has become widely used in
      the evaluation of pelvic floor function. The anorectal angle (ARA) is one
      parameter which is usually quantified during this examination. To determine the
      accuracy with which this measurement can be made, three physicians independently
      measured the resting and squeezing ARAs of 22 women. The coefficient of variation
      and the kappa statistic were used to describe the degree of agreement among the
      three examiners. These analyses revealed poor agreement among examiners for all
      22 patients taken as individuals, (kappa less than or equal to 0.40; mean
      coefficient of variation at rest = 18 percent; mean coefficient during squeezing
      = 21 percent). These results suggest that measurements of ARAs will vary among
      examiners for any particular patient, even though individual examiners may
      demonstrate consistency in recording ARA data. There is wide interobserver
      variation in the measurement of the ARA from lateral radiographs, making
      quantification an exercise of only limited clinical value.

PMID- 1991421
TI  - Subsite distribution and incidence of colorectal cancer in New Zealand, 1974
      1983.
AB  - The purpose of this study was to examine changes in subsite distribution and
      incidence of colorectal cancer within different age groups. Registration of
      colorectal cancer by the National Cancer Registry of New Zealand approached 100
      percent by 1974. The present study was based on 15,395 individuals aged 25 years
      and over and registered for colorectal cancer between 1974 and 1983. Subsite
      distribution (right colon, left colon, rectum) for different age groups (25-49,
      50-69, 70+ years) was significantly skewed, with an excess of right colonic
      cancer in individuals aged 25-49 years and 70+ years. This right colonic excess
      was accompanied by a relative reduction in left colonic cancer. Age adjusted
      incidence rates for the periods 1974-78 and 1979-83 were compared and stratified
      by age group and subsite. Incidence rates increased in all subsites in
      individuals aged 50+ years. This was particularly evident for right sided cancer
      in the elderly of both sexes. There was a marked reduction in the incidence of
      left colonic cancer and rectal cancer in individuals under 50 years. In contrast,
      the incidence of right colonic cancer remained relatively stable in young
      individuals. Time trend studies indicate that the skewed subsite distribution of
      large bowel cancer in different age groups may increase with time and is probably
      due to varying etiological factors acting on different cohorts.

PMID- 1991422
TI  - Treatment of anorectal abscess with or without primary fistulectomy. Results of a
      prospective randomized trial.
AB  - To determine whether primary fistulectomy should be performed or not at the time
      of incision and drainage, a prospective, randomized study in 70 patients with
      anorectal abscess was conducted. Thirty-six patients underwent incision, drainage
      and fistulectomy with primary partial internal spincterectomy (group I), whereas
      in 34 patients anorectal abscess was treated by incision and drainage alone
      (group II). After a median follow-up of 42.5 months, the combined recurrence or
      persistence rate was 2.9 percent in group I and 40.6 percent in group II (P less
      than 0.0003, log-rank test). Recurrent abscesses or persistent fistulas were
      treated by secondary partial internal sphincterectomy. Comparing anal continence
      before and 1 year after definite treatment, we found increased anal function
      disturbances in 39.4 percent of the patients in group I and in 21.4 percent of
      the patients in group II (P less than 0.106, Fisher-exact test). The combined
      recurrence or persistence rate of 40.6 percent indicates that more than half of
      the patients with anorectal abscess will have no further problems after simple
      incision and drainage. This finding, as well as the increased anal function
      disturbances after partial internal sphincterectomy (either primary or secondary)
      are the main reasons to reserve fistulectomy as a second stage procedure if
      necessary.

PMID- 1991423
TI  - Colorectal cancer: differences between community and geographically distant
      patients seen at an urban medical center.
AB  - Many studies in clinical oncology rely on hospital-derived patients. Hospitals
      vary in the proportions of patients from the local catchment area vs. those from
      more distant places, of whom a larger proportion are presumably referrals. To
      study the differences between these two types of patients, we analyzed 1,245
      colorectal cancer patients seen at a large urban medical center over a seven-year
      period. Three hundred ninety-eight patients were from the local community (32
      percent), 489 were from the extended community (39.3 percent), and 358 from more
      distant communities (28.8 percent). The patients from the local community tended
      to be older and from minority ethnic groups. In addition, the local community
      patients were more likely to have advanced disease at the time of presentation.
      The grade of the tumor and its site distribution within the large bowel were
      similar for the three groups. After adjusting for age, sex, race, and stage of
      disease, the survival was somewhat better for the distant community patients as
      compared with the local and extended communities (P less than 0.02). Overall, in
      our patient population, the distant patients tended to have more favorable
      socioeconomic factors and less advanced disease, and these differences may
      account, in large part, for a better prognosis for these patients. Particularly
      in large cooperative trials, studies may need to take into account the respective
      proportions of local community and geographically distant patients in analyzing
      and generalizing treatment outcomes.

PMID- 1991425
TI  - Reliability of anal pressure measurements.
AB  - This study investigates whether measurements of anal sphincter pressure and
      length are reproducible and whether visual analyses of manometric tracings are
      reliable. Manometric studies were performed on three different days in 10 male
      and 10 female healthy subjects with the use of a pneumohydraulic capillary
      perfusion system. There was complete agreement between both observers in the
      analysis of anal resting and squeeze pressure as well as sphincter length. The
      pressure profiles from different days correlated significantly (P less than 0.01)
      with each other regardless of whether the studies were performed in the prepared
      or unprepared bowel. However, anal sphincter length and the quality of the
      anorectal inhibitory reflex varied greatly on different days. Male and female
      subjects showed major differences in the capacity of the anal sphincter to
      contract voluntarily (P less than 0.01), but resting tone and sphincter length
      were comparable in the two groups. It is concluded that pressure determinations
      in the anal canal are reliable and reproducible, but that alterations in the
      quality of the anorectal reflex need to be confirmed by repeated measurements
      before pathology is diagnosed.

PMID- 1991424
TI  - Assessment of noninvasive intra-anal electromyography to evaluate sphincter
      function.
AB  - Assessment of anal function is now regarded as an important aspect of the
      proctologic examination in assessment of patients with disordered defecation.
      Conventional electromyography is invasive and often not repeatable because of
      patient discomfort. Noninvasive surface intra-anal EMG was evaluated as a method
      of assessing sphincter function in 76 subjects. A significant correlation was
      found between intra-anal EMG and anal manometry at rest and during a maximum
      squeeze effort (P less than 0.01). Intra-anal EMG was found to be reproducible
      when evaluated by 2 independent observers (P less than 0.05) and may prove a
      reliable portable noninvasive method of assessing sphincter function.

PMID- 1991426
TI  - The role of lasers in hemorrhoidectomy.
AB  - Eighty-eight patients who received treatment for hemorrhoids were randomized into
      two groups. Group A received the Nd-YAG laser phototherapy for internal
      hemorrhoid combined with the CO2 laser for external hemorrhoid. Group B was
      treated with closed Ferguson hemorrhoidectomy. The need of narcotic injections
      for pain relief was 11 percent in group A vs. 56 percent in group B (P less than
      0.001). The incidence of postoperative urinary retention was 7 percent in group
      A, vs. 39 percent in group B (P less than 0.05). No enema was required
      postoperatively in group A, vs. 9 percent in group B; 84 percent of the patients
      in group A were discharged on the second postoperative day, vs. 83 percent of the
      patients in group B discharged on the fifth postoperative day. The cost was 20
      percent less in the former group. The overall complications in both groups were
      insignificant in difference, except prolonged wound healing in group A was noted.
      One year follow-up showed satisfactory results. Laser treatment is considered one
      of the alternatives to conventional treatment, but the surgeon needs to be aware
      of laser hazards.

PMID- 1991427
TI  - Colonoscopic appendectomy: report of a case.
AB  - A persistent appendix occurred after inversion appendectomy. Colonoscopic removal
      was straightforward and would appear to be the treatment of choice in this
      unusual circumstance.

PMID- 1991428
TI  - A case of cecocolic intussusception with complete invagination and
      intussusception of the appendix with villous adenoma.
AB  - Villous adenoma of the appendix is a rare neoplasm and intussusception of the
      appendix is a rare pathologic condition. A very rare case seen in a 35-year-old
      male with pain in the right lateral abdomen is reported. In this patient, the
      appendix along with the villous adenoma intussuscepted and invaginated into the
      cecal lumen, and presented as cecocolic intussusception. A polypoid lesion was
      diagnosed in the cecum by fiberoptic colonoscopy. Unlike polypoid lesions at
      other sites in the large intestine, polypoid lesions of the cecum may accompany
      intussusception and invagination of the appendix. Consequently, caution is
      required in performing endoscopic polypectomy in cases of polypoid lesions of the
      cecum.

PMID- 1991429
TI  - Treatment of obstructive pneumatosis coli with endoscopic sclerotherapy: report
      of a case.
AB  - The case of an 86-year-old man with cardiac and pulmonary failure, in whom
      pneumatosis cystoides intestinalis caused segmental obstruction of the sigmoid
      colon is described. The patient was treated with endoscopic puncture and
      sclerotherapy of the cyst walls in four sessions, giving endoscopic and
      radiologic regress of the lesions and symptomatic relief.

PMID- 1991430
TI  - Enhancing blood glucose awareness in adolescents and young adults with IDDM.
AB  - OBJECTIVE: To determine the effectiveness of an intervention program designed to
      improve blood glucose awareness. RESEARCH DESIGN AND METHODS: Eight young-adult
      outpatients (mean age 22 yr) and six adolescent inpatients (mean age 14.5 yr)
      with insulin-dependent diabetes mellitus participated in the intervention
      program. Nine adolescent inpatients (mean age 13.9 yr) served as an untreated
      comparison group. One adult outpatient with unreliable data was removed. Before
      treatment, each patient completed a minimum of 40 blood glucose estimations,
      blood glucose tests, and symptom-rating checklists. Symptoms of hypo- or
      hyperglycemia were identified for each patient. The three-session intervention
      focused on internal (e.g., personal symptoms) and external (e.g., timing and
      amount of insulin, food, and exercise) cues that could be used to enhance blood
      glucose awareness. At postintervention, patients completed a minimum of 40
      additional blood glucose estimates and tests. Comparison subjects completed the
      pre-postassessments but did not receive the intervention. RESULTS: Blood glucose
      estimation accuracy was evaluated with error grid analysis. All estimated-actual
      blood glucose values were plotted into one of five zones: accurate estimates
      (zone A), benign errors (zone B), and clinically dangerous errors (zones C, D,
      and E). An overall accuracy index (AI) was calculated by subtracting the summed
      percentage of clinically dangerous estimates (zones C, D, and E) from the
      percentage of accurate estimates (zone A). At study entry, the adolescent
      inpatients' mean AI of 7% was significantly poorer than the 32% mean AI exhibited
      by the outpatient young-adult sample (P less than 0.02). At postintervention, the
      adolescents' mean AI improved to 30% (P less than 0.02) and the young adults'
      mean outpatient AI improved to 45% (P less than 0.06). The treated sample as a
      whole exhibited increased sensitivity to both hypo- (P less than 0.005) and
      hyperglycemia (P less than 0.05). Similar improvements did not occur in the
      untreated comparison sample. CONCLUSIONS: Adolescents may exhibit poorer blood
      glucose awareness than adults. Although this intervention program improved blood
      glucose awareness in both adolescent and adult patients, postintervention blood
      glucose estimation accuracy remained far from ideal.

PMID- 1991431
TI  - Racial differences in metabolic control of children and adolescents with type I
      diabetes mellitus.
AB  - OBJECTIVE: This study evaluated racial differences in the metabolic control of
      children and adolescents with insulin-dependent (type I) diabetes mellitus and
      examined the interactive effects of race with age and sex. RESEARCH DESIGN AND
      METHODS: Data on several demographic and clinical variables were obtained for 102
      black and 108 white children, including the percentage of total HbA1, age, age at
      diagnosis, duration of diabetes, pubertal status, insulin dose (U.kg-1.day-1),
      body mass index, number of clinic visits kept and missed, number of
      hospitalizations for diabetic ketoacidosis (DKA) for the year, and socioeconomic
      status (SES). RESULTS: Black children had higher insulin dosages (P less than
      0.05) and lower SESs (P less than 0.001) than white children. HbA1 was higher in
      black than white children (P less than 0.01) after statistically adjusting for
      the effects of insulin dose, diabetes duration, and SES. With HbA1-based
      criteria, more black than white children were in poor and fewer in good metabolic
      control (P less than 0.001). Older children (greater than or equal to 13 yr) had
      higher HbA1 levels than younger (less than 13 yr) children (P less than 0.002),
      but there were no differences in HbA1 between males and females nor were there
      interactive effects of race, sex, and age-group. Black children were hospitalized
      for DKA more frequently than white children (P less than 0.04). More black than
      white children missed clinic visits (P less than 0.01), but they did not differ
      in number of visits kept. CONCLUSIONS: Black youths with type I diabetes mellitus
      are in poorer metabolic control than white youths.

PMID- 1991432
TI  - Role of diabetologist in evaluating diabetic retinopathy.
AB  - OBJECTIVE: To evaluate the ability of diabetologists to screen diabetic patients
      for diabetic retinopathy. RESEARCH DESIGN AND METHODS: Comparison of eye
      examination performed by diabetologists with direct ophthalmoscopy through an
      undilated pupil and by ophthalmologists through a dilated pupil with seven-field
      stereoscopic fundus photography (gold standard). The study consisted of 67
      insulin-dependent and non-insulin-dependent diabetic outpatients attending a
      diabetes clinic. RESULTS: On the basis of fundus photography, patients were
      classified as having no or insignificant (30%), minimal (31%), moderate (24%), or
      severe (15%) retinopathy. The diabetologists and ophthalmologists performed
      similarly in their ability to classify severity of diabetic retinopathy
      accurately. When no or insignificant retinopathy (isolated microaneurysms only)
      was detected by examination, clinically significant retinopathy detected by
      fundus photography was highly unlikely (less than 5%). On the other hand, if more
      than isolated microaneurysms were seen on examination, all examiners missed more
      severe lesions detected by fundus photography. Patients with corrected visual
      acuity worse than 20/30 had a high likelihood (100%) of moderate or severe
      retinopathy. CONCLUSIONS: Motivated well-trained diabetologists can screen for
      diabetic retinopathy. The absence of detectable lesions by direct ophthalmoscopy
      indicates that automatic referral to an ophthalmologist is not necessary.
      However, if any level of retinopathy is detected or corrected acuity is worse
      than 20/30, referral to an ophthalmologist is required. In this setting, fundus
      photography is advised because it is the most sensitive means of detecting
      clinically significant retinopathy. If other nonophthalmologists can be trained
      to achieve similar results, current recommendations for ophthalmologic referral
      that require annual ophthalmologic examinations for most diabetic patients may
      need to be reconsidered.

PMID- 1991433
TI  - Care of diabetic patients by optometrists in New York State.
AB  - OBJECTIVE: This study was undertaken to learn about the involvement of
      optometrists in the eye care of diabetic patients in New York and to collect
      baseline data for planning intervention programs in diabetic eye disease.
      RESEARCH DESIGN AND METHODS: This study was conducted by a mail survey being sent
      to all optometrists in New York whom we could identify through state sources (n =
      2270). Three follow-up mailings were conducted. RESULTS: Eighty-six percent who
      received our mailing responded, 87% of whom reported that they see diabetic
      patients. Analysis was confined to this 87%. Routine retinal examinations were
      provided by 68% of the respondents who see diabetic patients, 62% of whom dilate
      the pupils. Sixty-eight percent who see diabetic patients diagnose retinopathy
      solely by their own examination, and 60% of these dilate. Follow-up of
      retinopathy was provided by 15% of optometrists who see diabetic patients, 90% of
      whom dilate the pupils of their diabetic patients. Twenty-five percent of
      respondents who see diabetic patients refer them to an ophthalmologist for
      diagnosis of retinopathy, and 67% refer all retinopathy patients to an
      ophthalmologist for follow-up. Although 91% of respondents recommended eye
      examinations at least annually for diabetic patients, only 68% specifically
      recommended annual examinations through dilated pupils. Those who dilate were
      significantly more likely to recommend annual dilated examinations than those who
      do not dilate, regardless of practice setting. CONCLUSIONS: These findings
      indicate that optometrists as a group see many diabetic patients. Intervention
      strategies should include increased emphasis on the use of dilation when
      examining diabetic patients and annual dilated retinal examinations.

PMID- 1991434
TI  - Demonstration of insulin transformation products in insulin vials by high
      performance liquid chromatography.
AB  - OBJECTIVE: To assess the importance of temperature, light, agitation, and regular
      withdrawal of insulin on the rates of appearance of three groups of insulin
      transformation products (ITPs) in vials of human and beef soluble insulin.
      RESEARCH DESIGN AND METHODS: Twelve insulin-treated patients (6 receiving human
      soluble insulin, 6 receiving beef soluble insulin) participated in the study.
      Reverse-phase high-performance liquid chromatography was used to measure ITP in
      serial samples from vials stored in various laboratory environments or issued to
      patients. Vials in the laboratory were analyzed on nine occasions over 26 wk;
      those issued to patients were analyzed weekly. RESULTS: Results were expressed as
      rates of change (% total protein/wk). Except for human insulin stored at 4
      degrees C, sampling did not accelerate transformation. Storage at higher
      temperatures caused more rapid transformation to all ITP groups, and human
      insulin was more susceptible than beef insulin. Exposure to light accelerated
      transformation mainly to group 3 ITP. Fibrillation occurred in beef but not human
      insulin carried in a shirt pocket. Results from patients' vials were consistent
      with reported storage conditions. CONCLUSIONS: All three ITP groups form in human
      and beef soluble insulin. Their rate of production is a function of temperature
      and light exposure. Differences between the two insulins were probably due to
      differences in formulation. Patients should be discouraged from hoarding vials
      and storing insulin in direct sunlight. One or more ITPs could contribute to the
      residual immunogenicity of modern insulin preparations.

PMID- 1991435
TI  - Major cross-country differences in risk of dying for people with IDDM. Diabetes
      Epidemiology Research International Mortality Study Group.
AB  - OBJECTIVE: Little is known concerning global differences in the risk of premature
      death for individuals developing youth-onset insulin-dependent diabetes mellitus
      (IDDM). The Diabetes Epidemiology Research International Study was developed to
      examine the mortality patterns of four population-based cohorts of IDDM cases
      from Allegheny County, Pennsylvania (n = 1000), Finland (n = 5146), Israel (n =
      681), and Japan (n = 1428). RESEARCH DESIGN AND METHODS: All subjects were
      diagnosed as having diabetes, were less than 18 yr old at onset, were taking
      insulin at the time of hospital discharge, and were diagnosed between 1 January
      1965 and 31 December 1979. The living status as of 1 January 1985 was determined.
      RESULTS: Overall, there were 182 deaths. Life-table analysis revealed that at 20
      yr duration of diabetes, 5.5% of the cohort had died in Allegheny County in
      contrast to only 3.1% in Finland and 4.6% in Israel (P less than 0.01). Follow-up
      for an additional 3 yr in the United States and Finland revealed major
      differences in the 30- to 39-yr age-group, with 3.9 times greater premature
      mortality in the U.S. cohort compared with the Finnish group (overall mortality
      2.3 vs. 0.6%, respectively). The Japanese cohort was developed in a somewhat
      different manner than the other three; therefore, the populations of the U.S.,
      Finland, and Israel were reconfigured to make them directly comparable to that of
      Japan. The Japanese cohort exhibited markedly higher age-adjusted mortality rates
      (n/100,000 person-yr of diabetes) than the other three (Japan 681, U.S. 230,
      Finland 171, and Israel 131). CONCLUSIONS: These data indicate that young adult
      IDDM subjects are at an increased risk of premature death, there are differences
      in the mortality risk across countries, and both the U.S. and Japan have the
      major problem of an apparently excessive premature death rate among young people
      who have diabetes.

PMID- 1991436
TI  - International evaluation of cause-specific mortality and IDDM. Diabetes
      Epidemiology Research International Mortality Study Group.
AB  - OBJECTIVE: A cross-cultural study was completed to evaluate differences in
      mortality patterns in four population cohorts in Japan; Israel; Allegheny County,
      Pennsylvania; and Finland. RESEARCH DESIGN AND METHODS: Cases were diagnosed
      between 1 January 1965 and 31 December 1979. Mortality was determined as of 1
      January 1985. There were 147 deaths occurring in the 8212 insulin-dependent
      diabetes mellitus (IDDM) patients in the four countries. A standardized protocol
      for assessing causes of death (cause-specific mortality) was developed; in this
      article, we report the causes. RESULTS: Major overall mortality differences by
      country appeared, with IDDM subjects in Japan much more likely to die than in the
      other countries. In Japan, the elevated mortality was the result of acute
      diabetes-related complications and kidney disease. For all countries, mortality
      from acute diabetes-related complications accounted for a surprisingly high
      percentage of deaths (greater than 25% in each country). A larger percentage of
      cases in Finland died as a result of suicide than for the other three countries.
      CONCLUSIONS: The results suggest that there are major cross-country differences
      in cause-specific mortality and that much of the premature mortality associated
      with diabetes is potentially preventable.

PMID- 1991437
TI  - Superiority of radiobinding assay over ELISA for detection of IAAs in newly
      diagnosed type I diabetic children.
AB  - OBJECTIVE: Liquid- or solid-phase assays have been used for insulin autoantibody
      (IAA) determination, and the method of IAA measurement has not been standardized.
      RESEARCH DESIGN AND METHODS: IAAs were determined by radiobinding assay (RBA) and
      enzyme-linked immunosorbent assay (ELISA) in two large age-matched groups of
      nondiabetic and newly diagnosed insulin-dependent (type I) diabetic children.
      RESULTS: Positivity for IAA by RBA (greater than or equal to nondiabetic mean +
      3SD) was 2 of 178 (1.1%) and 55 of 173 (32%) in nondiabetic and diabetic
      children, respectively. Prevalence of IAA by RBA was significantly higher in the
      youngest age-group (63% between 0-4 yr). Positivity for IAA by ELISA was 1 of 178
      (0.6%) and 8 of 169 (4.7%) in nondiabetic and diabetic children, respectively.
      Concordance rates between both assays were 0 of 3 (0%) in control subjects and 5
      of 58 (8.6%) in diabetic children. CONCLUSIONS: We conclude that RBA is more
      appropriate than ELISA for IAA detection at the onset of the disease. In
      addition, because available data suggest that IAAs detected by RBA only are high
      affinity antibodies, it is tempting to speculate that IAAs reflect a mature
      immune reaction against endogenous insulin.

PMID- 1991438
TI  - Serum levels of tumor necrosis factor and IL-1 alpha and IL-1 beta in diabetic
      patients.
AB  - OBJECTIVE: To determine whether chronic hyperglycemia causes increased levels of
      serum tumor necrosis factor (TNF) and interleukin 1 alpha (IL-1 alpha) and IL-1
      beta. RESEARCH DESIGN AND METHODS: Sera were obtained from 59 diabetic patients,
      44 chronically ill nondiabetic patients, and 34 age-matched healthy control
      subjects. Mononuclear cells were isolated from a subgroup of diabetic patients
      and healthy control subjects. RESULTS: Except for a modest increase in the
      prevalence of detectable serum TNF levels in diabetic patients, the serum
      cytokines measured in this study did not appear to be altered in diabetes. In
      vitro TNF production by mononuclear cells was not altered in diabetic patients.
      However, in vitro IL-1 beta secretion, in response to lipopolysaccharides, was
      reduced. CONCLUSIONS: Diabetes mellitus is not associated with significant
      changes in serum levels of TNF, IL-1 alpha, or IL-1 beta. In vitro secretion of
      IL-1 beta in response to lipopolysaccharides may be reduced in diabetes.

PMID- 1991439
TI  - Effect of motilin on gastric emptying in patients with diabetic gastroparesis.
AB  - OBJECTIVES: Because disturbances of gastric emptying are a serious complication
      in insulin-dependent diabetic subjects with regard to the maintenance of good
      metabolic control, we wanted to assess the effectiveness of motilin as a
      potential treatment for gastric emptying disturbances. RESEARCH DESIGN AND
      METHODS: The intestinal hormone motilin has been shown to accelerate gastric
      emptying in healthy subjects. Therefore, we examined the effect of intravenous
      motilin on gastric emptying of a 99mTc colloid-labeled semisolid test meal in 9
      insulin-dependent diabetic patients with diabetic gastroparesis. All patients had
      a significantly delayed gastric emptying rate compared with a group of 11 healthy
      control subjects. RESULTS: During the infusion of motilin, gastric emptying was
      accelerated, and it was no longer significantly different from control values.
      CONCLUSIONS: These data demonstrate that motilin and related compounds such as
      erythromycin derivatives could be useful for the treatment of disturbed gastric
      emptying in diabetic subjects.

PMID- 1991440
TI  - Vitamin E reduction of protein glycosylation in diabetes. New prospect for
      prevention of diabetic complications?
AB  - OBJECTIVE: This study evaluated the possibility of inhibiting protein
      glycosylation in vivo with vitamin E. RESEARCH DESIGN AND METHODS: Two groups of
      10 insulin-requiring diabetic patients, matched for duration of disease and
      metabolic control, received daily vitamin E supplementation of 1200 and 600 mg,
      respectively, for 2 mo. A third group of 10 diabetic patients, matched for
      duration of disease and metabolic control, served as the control group and
      received placebo. Fasting plasma glucose, mean daily plasma glucose, fasting
      labile HbA1, and glycosylated proteins were measured in the basal state and after
      1 and 2 mo of treatment. In addition, hyperglycemic clamp studies were performed
      in basal state and after 1 mo of vitamin E administration in all patients.
      RESULTS: Glycemic indices did not show any significant changes during the study,
      whereas fasting labile HbA, and glycosylated proteins decreased significantly
      after 1 and 2 mo in patients on vitamin E administration. Stable HbA1 decreased
      after 2 mo. Mean glycemic incremental area in the hyperglycemic clamp procedure
      was similar before and after treatment, whereas a significant reduction in mean
      labile HbA1 incremental area was found after vitamin E supplementation. A
      significant difference was also found in both fasting and incremental labile HbA1
      levels, stable HbA1, and glycosylated proteins between the two groups of diabetic
      patients on the two doses of vitamin E; the diabetic patients who received the
      higher dose of vitamin E showed the greater reduction. No significant changes in
      these parameters were observed in diabetic patients on placebo administration.
      CONCLUSIONS: These results demonstrate that vitamin E administration may reduce
      protein glycosylation in diabetic subjects independently of changes in plasma
      glucose, an effect that may be due to the inhibition of labile glycosylation, the
      first step of the Maillard reaction. Long-term studies will help establish the
      usefulness of vitamin E administration for the prevention of diabetic
      complications.

PMID- 1991441
TI  - Methodological issues in examination of fear of hypoglycemia.

PMID- 1991442
TI  - Insulin and atheroma in IDDM.

PMID- 1991443
TI  - Limitation in American Diabetes Association's position statement on diabetes and
      exercise.

PMID- 1991444
TI  - Relationship of limited joint mobility to abnormal foot pressures and diabetic
      foot ulceration.
AB  - OBJECTIVE: To investigate the role of limited joint mobility (LJM) in causing
      abnormal foot pressures and foot ulceration. RESEARCH DESIGN AND METHODS: The
      subjects were recruited from a general diabetes clinic where patients were
      screened for neuropathy, retinopathy, and elevated plantar foot pressure. Sixty
      four patients in five groups were matched by age and sex in the following groups:
      group 1, patients with LJM and neuropathy; group 2, nonneuropathic diabetic
      patients with LJM; group 3, patients with neuropathy and no LJM; group 4,
      diabetic control subjects; and group 5, nondiabetic control subjects. Joint
      mobility was assessed in the foot at subtalar and metatarsophalangeal joints;
      plantar foot pressures were assessed by optical pedobarography and neuropathic
      status by a Biothesiometer and electrophysiology. RESULTS: Joint mobility was
      reduced at both sites in groups 1 and 2 compared with groups 3, 4, and 5 (P less
      than 0.001). Plantar foot pressures were significantly higher in groups 1 and 2
      compared with groups 3, 4, and 5 (P less than 0.001). No differences in plantar
      foot pressures were observed between groups 1 and 2. There were strong
      correlations between plantar foot pressures and joint mobility in the foot (r = 
      0.7, P less than 0.001). Previous foot ulceration was present in 65% of patients
      in group 1, none in group 2, and 5% in group 3. CONCLUSIONS: 1) LJM may be a
      major factor in causing abnormally high plantar foot pressures, 2) abnormal
      plantar foot pressures alone do not lead to foot ulceration, and 3) LJM
      contributes to foot ulceration in the susceptible neuropathic foot.

PMID- 1991445
TI  - Interstitial lung disease.
AB  - The interstitial lung diseases are comprised of a group of pulmonary disorders
      characterized clinically by diffuse infiltrates on the chest radiograph and
      histologically by distortion of the gas exchanging portion of the lung. The
      physiologic correlates are restriction of lung volumes and impaired oxygenation.
      The term "interstitial" when applied to these diseases is actually a misnomer
      because it implies that the inflammatory process is limited specifically to the
      area between the alveolar epithelial and capillary endothelial basement
      membranes. The diseases currently grouped as "interstitial" also frequently
      involve the alveolar epithelium, alveolar space, pulmonary microvasculature, and
      less commonly, the respiratory bronchioles, larger airways, and even the pleura.
      The enormous differential diagnosis of interstitial lung disease can be made
      manageable by understanding that pneumoconiosis, drug-induced disease, and
      hypersensitivity pneumonitis account for over 80% of the responsible entities and
      can usually be identified from the patient's history. The nine remaining
      diseases/disease categories include: sarcoidosis, idiopathic pulmonary fibrosis,
      bronchiolitis obliterans-organizing pneumonia, histiocytosis X, chronic
      eosinophilic pneumonia, collagen vascular disease-associated interstitial lung
      disease, granulomatous vasculitis (Wegener's granulomatosis, Churg-Strauss
      syndrome, lymphomatoid granulomatosis), Goodpasture's syndrome, and pulmonary
      alveolar proteinosis. The diagnosis of a specific interstitial lung disease can
      be made via various means including the patient's history, specific serologies,
      bronchoalveolar lavage, transbronchial biopsy, and biopsy of extrathoracic
      tissues or open lung biopsy. A directed diagnostic approach can be formulated
      based on an understanding of these techniques and a thorough knowledge of the
      clinical presentations and specific diagnostic criteria for each of the major
      diseases. This monograph will serve as a guide for the clinician to use in
      evaluating and treating patients with interstitial lung disease. We begin by
      reviewing the clinical presentation, diagnostic criteria, and management of
      specific interstitial lung diseases excluding pulmonary infection, neoplasm, and
      sarcoidosis. Pneumoconiosis and drug-induced syndromes are not discussed in
      detail, but the agents responsible and pertinent exposures are presented in
      tabular form in the discussion of the general diagnostic approach.

PMID- 1991446
TI  - Inner membrane protease I, an enzyme mediating intramitochondrial protein sorting
      in yeast.
AB  - Several precursors transported from the cytoplasm to the intermembrane space of
      yeast mitochondria are first cleaved by the MAS-encoded protease in the matrix
      space and then by additional proteases that have not been characterized. We have
      now developed a specific assay for one of these other proteases. The enzyme is an
      integral protein of the inner membrane; it requires divalent cations and acidic
      phospholipid for activity, and is defective in yeast mutant pet ts2858 which
      accumulates an incompletely processed cytochrome b2 precursor. The protease
      contains a 21.4 kd subunit whose C-terminal part is exposed on the outer face of
      the inner membrane. An antibody against this polypeptide inhibits the activity of
      the protease. As overproduction of the polypeptide does not increase the activity
      of the protease in mitochondria, the enzyme may be a hetero-oligomer. This 'inner
      membrane protease I' shares several key features with the leader peptidase of
      Escherichia coli and the signal peptidase of the endoplasmic reticulum.

PMID- 1991447
TI  - The murine Spi-2 proteinase inhibitor locus: a multigene family with a
      hypervariable reactive site domain.
AB  - We have isolated 10 closely linked members of a proteinase inhibitor multigene
      family from the inbred mouse strain 129. These sequences, termed the Serine
      Proteinase Inhibitor 2 (Spi-2) genes, appear to have been derived from a common
      ancestor represented in man by the single copy alpha 1-antichymotrypsin gene. The
      genes are clustered on two cloned genomic DNA segments spanning 220 kb, and have
      at least partially retained the intragenic structure of the ancestral Spi-2 gene.
      Sequence analysis from the final coding exon indicates that most of the mouse
      genes may be competent to encode functional proteins, some with a predictable
      inhibitory spectrum, and several representing novel inhibitor types. An
      oligonucleotide probe designed to one reactive centre sequence enabled the
      isolation of the cognate expressed transcript from a liver cDNA library. However,
      whether expressed or not, the reactive centre regions of all the sequences have
      diverged at a rapid rate relative to structurally defined flanking sequences. The
      divergence is also appreciably greater than that occurring in an adjacent non
      coding sequence. This phenomenon has established novel potential inhibitory
      specificities, while maintaining a functional inhibitor structure.

PMID- 1991448
TI  - Distinct functions for thyroid hormone receptors alpha and beta in brain
      development indicated by differential expression of receptor genes.
AB  - Thyroid hormones are essential for correct brain development, and since
      vertebrates express two thyroid hormone receptor genes (TR alpha and beta), we
      investigated TR gene expression during chick brain ontogenesis. In situ
      hybridization analyses showed that TR alpha mRNA was widely expressed from early
      embryonic stages, whereas TR beta was sharply induced after embryonic day 19
      (E19), coinciding with the known hormone-sensitive period. Differential
      expression of TR mRNAs was striking in the cerebellum: TR beta mRNA was induced
      in white matter and granule cells after the migratory phase, suggesting a main TR
      beta function in late, hormone-dependent glial and neuronal maturation. In
      contrast, TR alpha mRNA was expressed in the earlier proliferating and migrating
      granule cells, and in the more mature granular and Purkinje cell layers after
      hatching, indicating a role for TR alpha in both immature and mature neural
      cells. Surprisingly, both TR genes were expressed in early cerebellar outgrowth
      at E9, before known hormone requirements, with TR beta mRNA restricted to the
      ventricular epithelium of the metencephalon and TR alpha expressed in migrating
      cells and the early granular layer. The results implicate TRs with distinct
      functions in the early embryonic brain as well as in the late phase of hormone
      requirement.

PMID- 1991450
TI  - The hematopoietic and epithelial forms of CD44 are distinct polypeptides with
      different adhesion potentials for hyaluronate-bearing cells.
AB  - CD44 is a polymorphic integral membrane protein which recognizes hyaluronate and
      whose proposed roles encompass lymphocyte activation, matrix adhesion and the
      attachment of lymphocytes to lymph node high endothelial venules (HEVs).
      Immunochemical and RNA blot data have supported the existence of two forms of
      CD44: a hematopoietic form expressed by cells of mesodermal origin (and by some
      carcinoma cell lines) and an epithelial form weakly expressed by normal
      epithelium but highly expressed by carcinomas. This report describes the
      isolation of a cDNA encoding a distinct CD44 polypeptide expressed by epithelial
      cells. Re-expression of each form of CD44 in a B cell line allowed cells
      transfected with the hematopoietic but not the epithelial form to bind to viable
      rat lymph node HEV cells in primary culture.

PMID- 1991449
TI  - Long-term proliferating early pre B cell lines and clones with the potential to
      develop to surface Ig-positive, mitogen reactive B cells in vitro and in vivo.
AB  - Cell lines and clones were established from PB76-positive mouse fetal liver at
      day 13 and 14 of gestation, which proliferated with division times of a day in
      serum-substituted cultures under the stimulatory influence of adherent stromal
      cells and the cytokine IL-7 for periods longer than half a year. These lines
      expressed varying levels of the B lymphocyte lineage related markers PB76, B220,
      BP-1, VpreB and lambda 5, but no surface Ig or MHC class II molecules. All clones
      expressed PB76, VpreB and lambda 5 in a high percentage of cells, while B220
      and/or BP-1 expression was low or undetectable in some. A cell line, and several
      clones established from it, all had kappa and lambda light chain genes in germ
      line configuration. Either one or both of their H-chain-gene containing
      chromosomes carried a DH to JH. These pre B cell lines and clones could be
      induced to VH to DH and VL to JL rearrangements. This resulted in the development
      of varying percentages of sIg-positive surface, MHC class II negative, LPS
      reactive B cells within 2-3 days, in the absence of contacts with stromal cells
      and/or IL-7. When injected into SCID mice, the cultured pre B cells populated the
      spleen of these mice to 5% with surface Ig-, MHC class II-positive LPS-reactive
      cells for greater than 25 weeks. The long-term in vitro proliferative capacity of
      these DH-JH rearranged pre B cell clones makes them major candidates for
      committed stem cells of the B lineage.

PMID- 1991451
TI  - Identification of regulatory residues of the yeast adenylyl cyclase.
AB  - We have attempted to identify amino acid residues of the yeast adenylyl cyclase
      that are involved in the regulation of its activity, by isolating adenylyl
      cyclase-linked spontaneous mutations capable of suppressing the temperature
      sensitive phenotype of ras1- ras2-ts1 strains. We previously identified a mutated
      adenylyl cyclase in which a single point mutation, called CR14, led to the
      replacement of threonine 1651 with isoleucine. We have now investigated the
      biological effects of CR14, and of other mutations that cause the replacement of
      threonine 1651 by distinct amino acids. We have observed that the response of
      adenylyl cyclase to Ras can be either enhanced or attenuated, without significant
      effects on the steady-state level of the former enzyme in vivo, depending on the
      amino acid side chain at position 1651. Therefore, this residue identifies a
      regulatory region on the adenylyl cyclase molecule. We have also taken advantage
      of the attenuation of adenylyl cyclase function caused by the replacement of
      threonine 1651 with aspartic acid to isolate intragenic suppressor mutations. We
      have identified several point mutations, leading to single amino acid
      substitutions, individually capable of reactivating the attenuated adenylyl
      cyclase. The corresponding amino acid changes are located within a relatively
      small region, including residues 1331, 1345, 1348 and 1374. This region could be
      physiologically involved in the negative control of the carboxy-terminal
      catalytic domain.

PMID- 1991452
TI  - Formation of nucleosomes on positively supercoiled DNA.
AB  - A transcribing RNA polymerase is thought to generate positive supercoils in front
      of the advancing transcription complex and negative supercoils behind. We have
      examined the possibility that positive supercoils might destabilize nucleosomes,
      facilitating transcription. We show that histone octamers bind to positively
      supercoiled DNA, and that after the complex is relaxed, 'classical' nucleosomes
      are present. We tested the possibility that nucleosomes on positively supercoiled
      DNA are in an altered (presumably more open) conformation, but revert to the
      classical structure only on release of this stress. However, circular dichroic
      spectra, and chemical cross-linking and modification of core histones, all
      suggest that the complexes initially formed on positively supercoiled DNA are
      classical nucleosomes. Although such structures are stable, their formation
      requires the plasmid to become more positively supercoiled, resulting in greater
      superhelical stress. In contrast, formation of nucleosomes on negatively
      supercoiled DNA relieves superhelical stress. In an exchange experiment in which
      equilibrium is achieved, nucleosomes transfer from positively to negatively
      supercoiled DNA, as predicted from the super-coiling free energies of the
      reactions. This suggests a mechanism for transcription of a gene assembled into
      chromatin, in which octamers are sequentially transferred from the region in
      front of the polymerase to the region behind.

PMID- 1991453
TI  - A novel splicing factor is an integral component of 200S large nuclear
      ribonucleoprotein (InRNP) particles.
AB  - In previous studies we have shown that nuclear transcripts of several pre-mRNAs
      can be released from nuclei of mammalian cells in the form of large nuclear
      ribonucleoprotein (InRNP) particles. By electron microscopy, these particles
      appeared as compact composite structures, 50 nm in diameter, which invariably
      sedimented at the 200S region in sucrose gradients. In order to identify putative
      protein splicing factors associated with the 200S InRNP particles, a panel of
      monoclonal antibodies directed against these particles were screened for their
      ability to inhibit splicing of pre-mRNA in vitro. In this study we have focused
      on a nuclear protein of 88 kd in molecular weight, which is an integral component
      of the InRNP complex and is recognized by monoclonal antibodies from a specific
      clone. This protein has been identified here as a novel splicing factor by, (i)
      antibody inhibition of splicing in vitro and (ii) depletion of splicing activity
      from HeLa cell nuclear extract after removing the 88 kd polypeptide by
      immunoadsorption, and complementation of the depleted activity with an affinity
      purified 88 kd antigen. This splicing factor has further been shown to be
      required for the assembly of an active splicing complex.

PMID- 1991454
TI  - Effect of cholic acid on the colonic sister chromatid exchange frequency induced
      by 1,2-dimethylhydrazine in C57BL/6 mice.

PMID- 1991455
TI  - Genotoxicity of the fungicide dichlofluanid in seven assays.
AB  - Seven different endpoints for detection of genotoxicity have been used to
      demonstrate the DNA-altering properties of Dichlofluanid, a fungicide commonly
      used in viticulture pest control. Each endpoint (DNA synthesis inhibition test,
      alkaline viscosimetry, umu-test, alkaline filter elution, FADU-test, 32P
      postlabeling, and electron microscopy) shows clear evidence of genotoxicity.
      These data indicate that application of the fungicide dichlofluanid may be
      mutagenic and/or carcinogenic for exposed humans.

PMID- 1991456
TI  - Single-strand breaks, chromosome aberrations, sister-chromatid exchanges, and
      micronuclei in blood lymphocytes of workers exposed to styrene during the
      production of reinforced plastics.
AB  - Chromosome aberrations (CA), micronuclei (MN, cytokinesis-block [CB] method), and
      sister-chromatid exchanges (SCE) were analysed in blood lymphocytes of 17 workers
      and 17 control subjects. The mean urinary mandelic acid level (average 9.4
      mmol/l) and styrene glycol in blood (average 2.5 mumol/l) implied exposure to
      about 300 mg/m3 of styrene in the plant. The number of CA was significantly
      higher in non-smoking workers compared with nonsmoking controls. A significant
      correlation was observed between duration of exposure and individual CA level of
      all workers. No significant effects were observed in MN or SCE. Single-strand
      breaks (SSB) in DNA of isolated lymphocytes were studied in nine of the workers
      and eight of the controls by the DNA-unwinding technique. The results showed an
      increase in SSB among the exposed workers. The present findings support earlier
      reports on the increase of structural CA in blood lymphocytes of workers in the
      reinforced plastic industry, and also show that SSBs are elevated in such
      workers.

PMID- 1991457
TI  - Induction of gastrointestinal tract nuclear anomalies in B6C3F1 mice by 3-chloro
      4-(dichloromethyl)-5-hydroxy-2[5H]-furanone and 3,4-(dichloro)-5-hydroxy-2[5H]
      furanone, mutagenic byproducts of chlorine disinfection.
AB  - Two chlorinated hydroxylated furanones, 3-chloro-4-(dichloromethyl)-5-hydroxy
      2[5H]-furanone (MX) and 3,4-(dichloro)-5-hydroxy-2[5H]-furanone (MA), are
      bacterial mutagens and they are also byproducts of chlorine disinfection, and
      frequent contaminants of drinking water. In this work MX is shown to induce
      nuclear anomalies in the gastrointestinal tract of the B6C3F1 mouse. The other
      chlorohydroxy-furanone, MA, gives suggestive evidence of activity. In this
      bioassay MX was approximately equivalent in potency to epichlorohydrin (ECH) but
      was much less potent than methylnitrosourea (MNU). The latter two chemicals are
      confirmed rodent gastrointestinal tract carcinogens. The duodenum was the most
      sensitive tissue responding with both increased numbers of nuclear anomalies per
      mouse and increased incidence of animals presenting the nuclear aberrations 24 hr
      after a single oral dose of 0.37 mmol/kg-1 of MX. MA also induced a significant
      increase in duodenal nuclear anomalies, but only at the highest dose (0.46
      mmol/kg-1). The proximal colon and forestomach responded to MX but not MA. This
      is the first study demonstrating that chlorohydroxyfuranones are capable of
      inducing nuclear toxicity in vivo. However, it is clear, for MX at least, that
      its potency in the gastrointestinal tract nuclear anomalies assay is not
      commensurate with its extreme bacterial mutagenicity. Since the gastrointestinal
      tract tissues are directly exposed to orally administered genotoxins, one
      possible explanation for the weak response observed in this study could be that
      mammalian cells can effectively detoxify chlorohydroxyfuranones.

PMID- 1991458
TI  - Quantitative structure-activity relationships of heterocyclic amine mutagens
      formed during the cooking of food.
AB  - The major protein-rich foods, particularly muscle meats, contain part-per-billion
      quantities of potent mutagens formed by frying or broiling to a well-done state.
      Related mutagens are formed by pyrolysis of amino acids or proteins and in heated
      model systems. The thermic mutagens so far identified are heterocyclic aromatic
      amines of aminoimidazo-azaarene (AIA) and aminocarboline classes. The chemicals
      require activation by enzymes to form metabolites reactive with nucleic acids.
      These thermic mutagens, and numerous synthetic congeners, exhibit an enormous
      range of potency as frameshift mutagens in the Ames/Salmonella assay. However,
      structural variations are nominal within the two classes. Structural parameters
      that appeared relevant to determining potency were selected for 38 AIAs and 23
      amino-carbolines. For the AIA class these were: the number of fused rings, the
      number of heteroatoms in Rings 2 and 3, methyl substitution on imidazo ring
      nitrogen atoms, and methyl substitution on ring carbon atoms. For the amino
      carboline class the structural parameters were: the position of the pyridine-type
      nitrogen atom in Ring 1, the substitution position of the exocyclic amino group
      on Ring 1, and methyl substitution on ring carbon atoms. These structural
      parameters may influence mutagenic potency in the following ways. 1) Electronic
      or steric effects may determine the reactivity and stability of the ultimate
      mutagenic metabolite. Optimal balance of reactivity and lifetime of this
      transient intermediate may be required for access to and reaction with nuclear
      DNA to cause mutations. 2) Substitution on the rings may block detoxication
      reactions. The structural parameters identified should prove useful in predicting
      the mutagenicity of untested compounds of these types.

PMID- 1991459
TI  - Salmonella typhimurium (TA100) mutagenicity of 3-chloro-4-(dichloromethyl)-5
      hydroxy-2(5H)-furanone and its open- and closed-ring analogs.
AB  - The mutagenicities of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX,
      compound 1), 3-chloro-4-(dichloromethyl)-2(5H)-furanone (RMX, compound 6), and 2
      (dichloromethyl)-3,3-dichloropropenal (TCB, compound 7) were determined in the
      same assay and in repetitive determinations using Salmonella typhimurium (TA 100)
      without microsomal fraction activation. In addition, the mutagenicity of 2-methyl
      3,3-dichloropropenal (compound 8) was assayed in the same manner although not
      simultaneously with MX, RMX, and TCB. This study was undertaken to ascertain the
      role of open- and closed-ring forms of MX in the mutagenicity of MX. MX proved to
      be roughly 100 times more mutagenic than the open-ring analogue TCB and 10 times
      more mutagenic than the closed-ring analogue RMX. Compound 8 was inactive. Assay
      stability of the three active compounds in Vogel-Bonner medium at 38 degrees C
      was estimated as the chemical half-life values by following the change in UV
      absorbance at selected wave lengths. Half-life values were 10.7, 2.6, and 2.8 hr,
      respectively, for MX, RMX, and TCB. The enhanced mutagenicity of MX relative to
      RMX and TCB is attributed to the intrinsic mutagenicity of MX and its greater
      stability is judged to play only a minor role. Moreover, the greater mutagenicity
      of the closed-ring analogue RMX relative to the open-ring analogue TCB points to
      the ring form of MX as the active species even though the open form of MX is
      predominant under assay conditions.

PMID- 1991460
TI  - Reproductive integrity of mammalian cells exposed to power frequency
      electromagnetic fields.
AB  - Human lymphocytes and Chinese hamster ovary (CHO) fibroblasts were analyzed for
      cytogenetic and cytotoxic endpoints to determine whether exposure to power
      frequency (60 Hz) electromagnetic fields (EMF) interferes with normal cell growth
      and reproduction. An exposure chamber was built to apply variable electric
      current densities of 3, 30, 300, and 3,000 microA/cm2, simultaneously with a
      fixed magnetic field of 2.2 G to proliferating cells. The current densities were
      chosen to bracket those that may be induced in the human body by fields measured
      beneath high voltage (765 kV) power transmission lines. The electric current was
      applied through the media of a cell culture chamber positioned between two
      stainless steel electrodes but separated from direct contact with the culture
      media by a salt bridge composed of a 1% agarose gel. The magnetic field was
      generated using two pairs of Helmholtz coils driven 73 degrees out of phase
      producing an elliptically polarized magnetic field 36 degrees out of phase with
      the electric field. The EMFs were measured and mapped inside the cell culture
      chamber to insure their uniformity. CHO cells were exposed continuously for 24-96
      hr (depending on experiment) and human lymphocytes were exposed continuously for
      72 hr. The EMFs were monitored throughout the entire treatment period using a
      multichannel chart recorder to verify continuous application of the desired
      fields. Sister-chromatid exchange and micronuclei were monitored to evaluate the
      potential for genotoxicity. In addition, standard growth curves, clonogenicity,
      and cell cycle kinetics were analyzed to evaluate possible cytotoxic effects. The
      experimental data consistently showed that the growth rate and reproductive
      integrity of both cell types was unaffected by exposure to the electromagnetic
      fields.

PMID- 1991462
TI  - Failure of channelling to maintain low concentrations of metabolic intermediates.
AB  - Computer modelling has been used to investigate the effect of direct transfer of
      metabolites between consecutive enzymes (channelling) on the free concentrations
      of the channelled metabolites. When a channelled intermediate cannot participate
      in any other reactions, any increase in channelling tends to increase its free
      concentration, albeit very slightly, unless the increase in net flux brought
      about by the channel is compensated for by a simultaneous decrease in the
      activity of the route through the free intermediate, in which case channelling
      has no effect at all on the free steady-state concentration of the channelled
      intermediate. If the free intermediate is capable of participating in side
      reactions, channelling can decrease these side reactions, but only slightly
      unless virtually all of the final product results from flux through the channel
      and the rate constants for the direct pathway are virtually zero. In general,
      channelling appears not to provide a useful mechanism for maintaining
      intermediate concentrations at low levels.

PMID- 1991461
TI  - Aerial oxidation of hydrazines to nitrosamines.
AB  - When 1,1-dimethylhydrazine and N-aminopiperidine were deliberately exposed to air
      substantial amounts of the corresponding carcinogenic nitrosamines were formed.
      Unoxidized samples of 1,1-dimethylhydrazine were not mutagenic while oxidized
      samples (which contained much higher levels of nitrosamines) were mutagenic. Both
      unoxidized and oxidized samples of N-aminopiperidine were mutagenic.

PMID- 1991464
TI  - Fe3+(2)-transferrin and Fe3+(2)-asialotransferrin deliver iron to hepatocytes by
      an identical mechanism.
AB  - We have been unable to demonstrate the unequivocal presence of transferrin
      receptors on rat hepatocytes. The binding and presumed internalisation of 125I
      Fe3+(2)-transferrin by freshly isolated hepatocytes was only partially inhibited
      by up to a 10(4)-fold molar excess of unlabelled ligand and was virtually
      insensitive to chloroquine. There would appear to be only a weak association
      between this ligand and some component of the hepatocyte cell surface. These
      results were not compatible with the commitment of Fe3+(2)-transferrin to either
      a receptor-mediated endocytotic pathway nor to a rapid recycling pathway through
      sorting endosomes. Desialylation of the biantennary oligosaccharide side chains
      of Fe3+(2)-transferrin engendered a low affinity (Kd greater than or equal to
      0.25 microM) for the asialoglycoprotein receptor. 125I-Fe3+(2)-asialotransferrin
      was only superficially internalised by isolated hepatocytes but this was
      characteristic of ligands for the asialoglycoprotein receptor which have only
      biantennary (or single triantennary) side chains. This was also incompatible with
      the delivery of the ligand to sorting endosomes where the release of iron has
      been presumed to occur. Despite the different properties of the two ligands, the
      rates of iron uptake from 59Fe3+(2)-transferrin and 59Fe3+(2)-asialotransferrin
      were identical, suggesting a common mechanism for the translocation of iron
      across the plasma (or possibly endosomal) membrane such as a transmembrane
      oxidoreductase. Competition studies with unlabelled ligand or impermeable ferric
      ammonium citrate gave an IC50 of 1-15 micrograms Fe3+/ml for this process. The
      absence of transferrin receptor from the surface of the terminally
      differentiated, quiescent hepatocyte would be compatible with the dual roles
      suggested for transferrin as an iron transport protein and as a growth factor.
      The release of iron at the hepatocyte cell surface would effectively uncouple the
      two functions and render the hepatocyte unresponsive to growth stimulation by
      transferrin.

PMID- 1991463
TI  - Substrate specificity of alpha 2----3-sialyltransferases in ganglioside
      biosynthesis of rat liver golgi.
AB  - The acceptor specificities of four sialytransferases (I, II, IV and V) involved
      in ganglioside biosynthesis were studied in Golgi vesicles derived from rat
      liver. The activities of these sialytransferases were strongly detergent
      dependent. Competition experiments with different detergent concentrations using
      LacCer (Gal beta 1----4Glc beta 1----1Cer), GM1a [Gal beta 1----3GalNAc beta 1---
      4(NeuAc alpha 2----3)Gal beta 1----4Glc beta 1----1Cer] and GD1b [Gal beta 1---
      3GalNAc beta 1----4(NeuAc alpha 2----8NeuAc alpha 2----3)Gal beta 1----4Glc beta
      1----1Cer] as substrates, and as mutual inhibitors for ganglioside
      sialyltransferase activity, suggested that sialyltransferase IV was able to
      catalyze the sialyltransfer in alpha 2----3 linkage to the galactose residues of
      LacCer as well as of GM1a and GD1b. The other three sialyltransferases (I, II and
      V) seemed to be quite specific for their respective glycolipid acceptors, LacCer,
      GM3 and GM1b, GD1a and GT1b. Furthermore the kinetic data showed that
      sialyltransferase I was inactive at higher detergent concentrations (greater than
      75 micrograms Triton CF-54); under these conditions, formation of GM3 and GD1a
      was catalyzed only by sialyltransferase IV. These results have been integrated
      into a model for ganglioside biosynthesis and its regulation.

PMID- 1991465
TI  - The vacuolar protein-targeting signal of yeast carboxypeptidase is functional in
      oocytes from Xenopus laevis.
AB  - Carboxypeptidase Y, a yeast vacuolar glycoprotein was expressed in oocytes from
      Xenopus laevis and its biosynthesis and sorting were examined. In yeast,
      targeting to the vacuole, the functional equivalent of the lysosome, is not
      mannose-6-phosphate-receptor dependent. It was found that carboxypeptidase enters
      the secretory pathway of the oocyte and is there glycosylated, phosphorylated in
      the carbohydrate part and delivered to the lysosome. Deletion of an amino acid
      sequence, previously shown to determine intracellular targeting of this enzyme in
      yeast, caused a loss of phosphorylation and mislocalization of carboxypeptidase Y
      into the oocyte medium. Inhibition of glycosylation of carboxypeptidase by
      tunicamycin did not lead to its secretion. In-frame fusion of the targeting
      domain to a secretory yeast glycoprotein, invertase, did not prevent its
      secretion. However, a hybrid containing 80% carboxypeptidase abolished invertase
      secretion. The results indicate that the vacuolar protein-targeting signal from
      yeast carboxypeptidase can, in principal, function in a higher eukaryote.

PMID- 1991466
TI  - Analysis of inhibitor binding to the mitochondrial cytochrome c reductase by
      fluorescence quench titration. Evidence for a 'catalytic switch' at the Qo
      center.
AB  - The binding characteristics of inhibitors of the mitochondrial cytochrome c
      reductase were studied by fluorescence quench titration. Based on the standard
      binding equation, the applied numerical method allowed the online recorded
      titration curves to be interpreted by fitting the Kd, the number of binding
      sites, and the specific fluorescence of the free and the bound inhibitor. For the
      Qi center, 2-n-nonyl-4-hydroxyquinoline N-oxide and for the Qo center (E)-beta
      methoxyacrylate-stilbene (MOA-stilbene) were used as fluorescing inhibitors. The
      experiments could be extended to other, non-fluorescing inhibitors by competition
      analysis. Using this method we were able to compare the binding behaviour of Qi
      and Qo center inhibitors under different redox states of the enzyme using the
      same experimental set up. We studied the competition between inhibitors of the
      cytochrome c reductase representative for all subgroups and demonstrated that at
      least three inhibitor binding sites exist, two located in the Qo center, one
      located in the Qi center. Determination of the dissociation constants of the
      oxidized, the partially reduced and the fully reduced enzyme showed that
      inhibitor binding at the Qi center is not redox-dependent. In contrast, the
      binding of MOA-stilbene to the Qo center is decreased after reduction of the iron
      sulfur center and cytochrome c1, whereas this redox change increases the affinity
      for a Qo center inhibitor of the hydroxynaphthoquinone type, 3-n-undecyl-2
      hydroxynaphthoquinone. From these results, aware of the fact that the inhibitory
      mechanism at the Qo center is a non-competitive one, we made the hypothesis of a
      'catalytic switch' to explain both the bifurcation of electron flow and the
      inhibition at the Qo center. A steric blockage of one of two conformational
      states could serve as a cogent explanation for the great structural variability
      of the inhibitors and differential effects on the redox centers exerted by the
      inhibitors. Moreover, the proposed 'switch' gives some insight into other
      experimental results which are difficult to explain with the ubiquinone cycle as
      currently formulated.

PMID- 1991467
TI  - The human leukocyte-adhesion ligand, intercellular-adhesion molecule 2.
      Expression and characterization of the protein.
AB  - The leukocyte cell-adhesion receptors, complexes of the cluster of
      differentiation antigen 11a with cluster of differentiation antigen 18
      (CD11a/CD18), cluster of differentiation antigen 11b with cluster of
      differentiation antigen 18 (CD11b CD18) and cluster of differentiation antigen
      11c with cluster of differentiation antigen 18 (CD11c CD18), are of major
      importance in several leukocyte functions. Previously a cellular ligand named
      intercellular-adhesion molecule 1 (ICAM-1) was identified, isolated and
      extensively characterized. Recently a second similar molecule, intercellular
      adhesion molecule 2 (ICAM-2), was found by a functional DNA-cloning method. We
      have now synthesized the ICAM-2 DNA by the polymerase chain reaction (PCR),
      sequenced it, and transferred it into mammalian and bacterial expression vectors.
      A functional leukocyte-binding glycoprotein was obtained by transfection of COS-1
      cells. A soluble protein-A - ICAM-2 fusion protein was made in Escherichia coli,
      purified and used for antiserum production. The antiserum precipitated a cell
      surface protein with an apparent molecular mass of 55 kDa from ICAM-2 transfected
      COS-1 cells, leukocytes and endothelial cells, and inhibited leukocyte binding to
      transfected COS-1 cells. The bacterial fusion protein, lacking carbohydrate,
      specifically bound to leukocyte receptors.

PMID- 1991468
TI  - Endopeptidase variations among different life-cycle stages of African
      trypanosomes.
AB  - Lysates of different life-cycle stages of Trypanosoma congolense, Trypanosoma
      vivax and Trypanosoma brucei were analysed for endopeptidase activity, using
      reaction conditions which permitted a distinction to be made between lysosomal
      and non-lysosomal activity [Lonsdale-Eccles, J. D. & Grab, D. J. (1987) Eur. J.
      Biochem. 169, 467-475]. Hydrolysis of Z-Arg-Arg-NHMec (Z = benzyloxycarbonyl,
      NHMec = 7-amino-4-methylcoumaryl) and Z-Gly-Gly-Arg-NHMec occurred predominantly
      at alkaline pH and was observed in lysates of both insect and mammalian infective
      forms of T. brucei and T. congolense. Compared to their other life-cycle stages,
      procyclic forms of T. brucei and epimastigote forms of T. congolense exhibited
      enhanced hydrolysis of these substrates. Low levels of hydrolysis of Z-Arg-Arg
      NHMec were observed in the bloodstream and epimastigote forms of T. vivax. The
      hydrolysis of Z-Gly-Gly-Arg-NHMec in each of the life-cycle stages of T. vivax
      was generally below detectable levels. In lysates of T. congolense, proteolytic
      and Z-Phe-Arg-NHMec-hydrolytic activity in bloodstream forms greater than
      metacyclic greater than epimastigote greater than procyclic forms. In T. vivax Z
      Phe-Arg-NHMec-hydrolytic activity differed slightly according to the origin of
      the parasite but, in general, followed the same pattern (i.e. bloodstream forms
      greater than epimastigote forms, with metacyclic forms usually intermediate
      between these two). In T. brucei, Z-Phe-Arg-NHMec-hydrolytic activity in
      bloodstream forms greater than procyclic forms. Upon differentiation of the long,
      slender bloodstream forms into short, stumpy forms the Z-Phe-Arg-NHMec-hydrolytic
      activity was elevated even further. Thus, during their life cycle, each of these
      African trypanosomes exhibits complex changes of endopeptidase activity,
      suggestive of an induction of lysosomal activity between the insect and mammalian
      forms.

PMID- 1991469
TI  - The amphiphilic alpha-helix concept. Consequences on the structure of
      staphylococcal delta-toxin in solution and bound to lipids.
AB  - Staphylococcal delta-toxin, a synthetic analogue and a fragment were studied in
      order to determine their structure in solution and bound in lipids. In solution,
      a self-association process is observed. Analytical ultracentrifuge and quasi
      elastic light-scattering experiments suggest an isodesmic aggregation in the high
      concentration domain above 2 microM up to very large asymmetrical species.
      Decreasing concentrations below 2 microM of delta-toxin and the analogue allows
      dissociation, probably into monomers. The self-associated species are essentially
      alpha-helical (70%) with buried and highly immobilized Trp either at position 15
      for natural delta-toxin or 16 for the analogue. At the lowest concentration
      studied, the alpha-helix content severely decreases down to 35% while Trp
      fluorescence shows that these residues are exposed to buffer. The fragment 11-26
      is always monomeric and structureless. From all the data, a structural model of
      aggregated species is proposed with stacked antiparallel amphipathic rods. When
      bound to lipids, whatever their initial structure in solution, 26-residue long
      peptides mainly adopt an alpha-helix conformation (80%) while fragment 11-26
      exhibits about 50% alpha-helix. The lipid-peptide interactions were
      quantitatively analysed. For fragment 11-26, a single-step mechanism fits the
      spectroscopic changes and defines a single monomeric bound structure. On the
      other hand, for the 26-residue-long analogue, multiple-step processes must occur.
      The data were analysed with a partition of tetramers into lipids followed by a
      partial dissociation. Finally, the affinity of fragment 11-26 severely decreases
      from micelles to fluid and gel-state bilayers. The partition coefficient of the
      delta-toxin analogue is higher than those of other more apolar peptides, such as
      melittin and alamethicin, correlating with Eisenberg's hydrophobic moments. It is
      therefore proposed that delta-toxin probably lies parallel to the surface, only
      penetrating weakly in lipids, depending on their packing.

PMID- 1991470
TI  - Highly purified pea chloroplast RNA polymerase transcribes both rRNA and mRNA
      genes.
AB  - Pea chloroplast RNA polymerase has been obtained with about 2000-fold
      purification using DEAE-cellulose and phosphocellulose chromatography. The
      purified enzyme contained ten prominent polypeptides of 150, 130, 115, 110, 95,
      85, 75, 48, 44 and 39 kDa and four other minor polypeptides of 90, 34, 32 and 27
      kDa. Purification of this enzyme using chloroplast 16S rDNA promoter affinity
      column chromatography also yielded an enzyme with similar polypeptides. Purified
      polyclonal antibodies against the purified chloroplast RNA polymerase were found
      to recognize most of the polypeptides of the enzyme in Western blot experiments.
      Primary mobility shift of the 16S rRNA gene and ribulose-1,5-bisphosphate
      carboxylase large subunit (rbc-L) gene promoters observed with the chloroplast
      RNA polymerase was abolished by these antibodies. The specific in vitro
      transcription of these rRNA and mRNA genes was also inhibited by these
      antibodies. The transcription of the rRNA and mRNA genes was also abolished by
      tagetitoxin, a specific inhibitor of chloroplast RNA polymerase. The chloroplast
      RNA polymerase was found to bind specifically to the chloroplast 16S rRNA gene
      promoter region as visualized in electron microscopy. The presence of the
      polypeptides of 130, 110, 75-95 and 48 kDa in the DNA-enzyme complex was
      confirmed by a novel approach using immunogold labeling with the respective
      antibodies. The polypeptides of this purified RNA polymerase were found to be
      localized in chloroplasts by an indirect immunofluorescence.

PMID- 1991471
TI  - Specific valylation identity of turnip yellow mosaic virus RNA by yeast valyl
      tRNA synthetase is directed by the anticodon in a kinetic rather than affinity
      based discrimination.
AB  - Variants with mutations in three parts of the tRNA-like structure of turnip
      yellow mosaic virus RNA (the anticodon, the discriminator position in the amino
      acid acceptor stem, and in the variable loop) were created via site-directed
      mutagenesis of a cDNA clone and transcription with T7 RNA polymerase. The
      valylation properties of transcripts were studied in the presence of pure yeast
      valyl-tRNA synthetase. Mutation of the central position of the anticodon triplet
      resulted in a quasi-total loss of valylation activity, indicating that the
      anticodon is a principal determinant for valylation of the turnip yellow mosaic
      virus tRNA-like structure. These anticodon mutants interacted with yeast valyl
      tRNA synthetase with affinities comparable to those of the wild-type RNA and
      behaved as competitive inhibitors in the valylation reaction of yeast tRNAVal.
      The defective aminoacylation of these mutants therefore results from kinetic
      rather than affinity effects. Minor negative effects on valylation efficiency
      were observed for mutants with substitutions at the two other sites studied,
      suggesting a structural role or a limited contribution to the valine identity of
      the tRNA-like molecule.

PMID- 1991472
TI  - Mechanism of the inhibition of alpha-thrombin by hirudin-derived fragments
      hirudin(1-47) and hirudin(45-65).
AB  - The kinetic mechanism of the inhibition of alpha-thrombin by hirudin was analyzed
      using the hirudin-derived fragments hirudin(1-47) and hirudin(45-65). Previously,
      these fragments have been shown to interact with alpha-thrombin at distinct sites
      inhibiting thrombin-mediated clot formation. Binding to the active site the N
      terminal fragment hirudin(1-47) competitively inhibits hydrolysis of the
      substrates Tos-Gly-Pro-Arg-NH-Mec (Tos, tosyl; NH-Mec, 4-methylcoumaryl-7-amide)
      and fibrinogen with Ki values of 420 +/- 18 nM and 460 +/- 25 nM, respectively.
      Interacting with the anion-binding site of alpha-thrombin the C-terminal fragment
      competitively inhibits the hydrolysis of fibrinogen with a Ki of 760 +/- 40 nM.
      It was found, however, that this fragment acts as a hyperbolic uncompetitive
      inhibitor with respect to the hydrolysis of the peptide-NH-Mec substrate.
      According to the Botts-Morales scheme for enzyme inhibition, the parameters Ki =
      710 +/- 38 nM, K'i = 348 +/- 22 nM, as well as alpha = beta = 0.49 of thrombin
      inhibition by the C-terminal fragment hirudin(45-65), were obtained. The results
      are discussed in terms of the interaction of hirudin and thrombin.

PMID- 1991473
TI  - NMR investigations of the N-linked oligosaccharides at individual glycosylation
      sites of human lutropin.
AB  - Human lutropin or luteinizing hormone (hLH) is a heterodimeric glycoprotein,
      composed of two subunits. hLH alpha (N-glycosylated at Asn52 and Asn78) and hLH
      beta (N-glycosylated at Asn30). The sugar chains were liberated by hydrazinolysis
      from intact hLH beta and from glycopeptides obtained after tryptic digestion of
      hLH alpha, subsequently reduced and fractionated as alditols by anion-exchange
      and ion-suppression amine-adsorption HPLC and identified mainly by one
      dimensional (1D) and two-dimensional (2D) 1H-NMR spectroscopy. The results
      indicate predominantly diantennary. N-acetyllactosamine-type structures at all
      three glycosylation sites. The oligosaccharides attached to Asn52 (hLH alpha) and
      Asn30 (hLH beta) show a remarkably similar pattern, with mainly chain-terminating
      4-sulphated 2-deoxy-2-N-acetylamino-D-galactose (GalNAc) and a
      sulphated/sialylated structure as the major single component. However, virtually
      all N-glycans on the beta subunit bear a fucose residue alpha 1-6-linked to the
      proximal GlcNAc, whereas those at Asn52 (and Asn78) of the alpha subunit are
      predominantly non-fucosylated. The oligosaccharides at Asn78 (hLH alpha) are
      sialylated rather than sulphated and contain the unique sequence NeuAc alpha 2-6
      GalNAc beta 1-4GlcNAc beta 1-2 Man alpha 1-3 as part of the majority of mono- and
      disialylated compounds. The major single constituent at Asn78 has the following
      structure: [formula, see text]

PMID- 1991474
TI  - Rapid characterization of asparagine-linked oligosaccharides isolated from
      glycoproteins using a carbohydrate analyzer.
AB  - Chromatographic methods were developed for the separation and characterization of
      acidic (sialylated) and neutral (asialo-complex and high-mannose)
      oligosaccharides released from glycoproteins with peptide N-glycosidase F. endo
      beta-N-acetylglucosaminidase F and endo-beta-N-acetylglucosaminidase H using a
      carbohydrate analyzer (Dionex BioLC). All the carbohydrate separations were
      carried out on a polymeric pellicular anion-exchange column HPIC-AS6/CarboPac PA
      1 (Dionex) using only two eluants namely, 0.5 M NaOH and 3% acetic acid/NaOH pH
      5.5, which were mixed with water to generate various gradients. Developed
      conditions for quantitative detection of carbohydrates with pulsed amperometry
      were necessary to obtain steady baselines at 0.1-0.3 microA output with suitable
      sensitivity (less than 5 pmol) in separations employing a variety of acidic and
      alkaline sodium acetate gradients. Oligosaccharides released from heat-denatured
      and trypsin-treated glycoproteins were purified initially from large-scale
      digestion (greater than 0.1 g) by extraction of peptide material into
      phenol/chloroform and finally by ion-exchange chromatography of the acqueous
      phase. Oligosaccharides isolated from the peptide N-glycosidase digests of bovine
      fetuin, human transferrin and alpha 1-acid glycoprotein gave multiple peaks in
      each charge group in separations based on the charge content at pH 5.5. Alkaline
      sodium acetate gradients were developed to obtain oligosaccharide maps of the
      glycoproteins within 60 min, in which separated oligosaccharides eluted in the
      order of neutral, mono-, di-, tri- and tetra-sialylated species based on both
      charge, size and structure. Baseline separations were obtained with neutral
      oligosaccharide types but mixtures of high-mannose and complex types were poorly
      resolved. The high-mannose peaks were eliminated specifically from complex
      oligosaccharides by digesting with alpha-mannosidase. Treatment with beta
      galactosidase, beta-N-acetylglucosaminidase and alpha-mannosidase resulted in a
      decrease of the oligosaccharide elution times corresponding to the number of
      sugar residues lost, the profile of changes was highly reproducible. In contrast,
      treatment with alpha-L-fucosidase, endo-beta-N-acetylglucosaminidase F and endo
      beta-N-acetylglucosaminidase H resulted in an increase in their corresponding
      oligosaccharide retention times similar to the presence of an additional sugar
      residue. Conditions developed for separation of the reduced oligosaccharides and
      also a mixture of monosaccharide to oligosaccharide containing about 15 sugar
      residues within 30 min were useful in determining the effect of endo- and exo
      glycosidases on porcine thyroglobulin oligosaccharides. Changes in elution time
      of the oligosaccharides following specific glycosidase digestions combined with
      methylation analysis provided a rapid and sensitive tool for confirmation of the
      carbohydrate primary structures present in thyroglobulin.

PMID- 1991475
TI  - NMR studies of bipyrimidine cyclobutane photodimers.
AB  - Cyclobutane-type photodimers of dinucleoside monophosphates dCpdT, dTpdC and
      dTpdT were prepared by ultraviolet irradiation in the presence of acetophenone as
      photosensitizer. The cytosine-containing derivatives were found to deaminate
      forming uracil products. Using one- and two-dimensional NMR, the photoproducts
      were characterized as cis-syn and trans-syn cyclobutane photodimers. On the basis
      of NOE data the structures of the cis-syn and trans-syn products of dUpdT were
      determined using distance-geometry and restrained-energy-minimization methods.
      The cis-syn structures showed (high-ANTI/SYN)/high-ANTI glycosidic linkages while
      the trans-syn structures were in the SYN-ANTI region. The backbone conformations
      of both structures were in fair agreement with the coupling-constant-data. The
      trans-syn structures were found to be very rigid and similar in all three
      products. For the three cis-syn structures more conformational freedom and more
      variation among the three structures was observed.

PMID- 1991476
TI  - Thymidine kinase from Tetrahymena thermophila. Purification and immunological
      analysis.
AB  - Thymidine kinase is an enzyme involved in DNA precursor metabolism and DNA
      replication. The synthesis of this enzyme is highly regulated during the cell
      cycle and the activity of the enzyme is also regulated by feedback inhibition.
      Genes encoding thymidine kinase have been extremely useful as selectable markers
      for introducing DNA into a number of cells. In order to study cell cycle
      regulation of thymidine kinase, the gene which encodes this enzyme, as well as
      aspects of DNA replication in the ciliated protozoan Tetrahymena thermophila, we
      have purified thymidine kinase from Tetrahymena. Two forms of thymidine kinase
      with native molecular masses of 59 kDa and 80 kDa have been identified and
      purified 6800- and 4600-fold, respectively. The 59-kDa enzyme, a homodimer of 30
      kDa subunits, has been purified to near homogeneity and polyclonal antibodies
      have been raised against the 30-kDa subunit. Serological studies indicate that
      the two enzymes are antigenically distinct. The antibody against the Tetrahymena
      protein cross-reacts with a polypeptide in Chinese hamster ovary (CHO) cell
      extracts of 26 kDa which corresponds to the reported size of Chinese hamster
      thymidine kinase protein.

PMID- 1991477
TI  - Purification of a cysteine endopeptidase which is secreted with bioactive
      peptides from the epidermal glands of Xenopus laevis.
AB  - The purification is reported of an endopeptidase, XSCEP1 (Xenopus skin cysteine
      endopeptidase), present in skin secretions of Xenopus. The procedure involved an
      initial concentration of the enzyme by batchwise anion-exchange chromatography
      and ammonium sulphate precipitation. The proteolytic activity, determined with Z
      Phe-Arg-Amc (Z, benzyloxycarbonyl; Amc, 7-amidomethylcoumarin) as substrate, was
      fractionated by gradient ion-exchange chromatography, yielding a major component
      which was purified to homogeneity by chromatography on an organomercury-agarose
      column. SDS/PAGE demonstrated the presence of a single protein with a molecular
      mass of 27 kDa. The purified enzyme, which possessed a pH optimum of 5.5,
      exhibited the properties of a cysteine endopeptidase; it was activated by
      dithiothreitol and EDTA and inhibited by the mechanism-based inhibitor trans
      epoxysuccinyl-L-leucylamido(4-guanidino)butane. XSCEP1 exhibited a marked
      preference for substrates with a hydrophobic residue in the P1 position and
      arginine in the P2 position as opposed to a substrate with arginine residues in
      both positions. The enzyme was also able to cleave a Val-Arg-Gly sequence in a
      model substrate, reflecting cleavages undergone by a number of peptides present
      in Xenopus skin. The results point to a functional role for XSCEP1 as a putative
      processing enzyme.

PMID- 1991478
TI  - Mechanism and energetics of a citrate-transport system of Klebsiella pneumoniae.
AB  - The citrate-transport determinant of plasmid pES1 from Klebsiella pneumoniae
      [Schwarz, E. & Oesterhelt, D. (1985) EMBO J. 4, 1599-1603] has been subcloned in
      Escherichia coli DH1. Uptake of citrate in E. coli membrane vesicles via this
      uptake system is an electrogenic process, although the pH gradient is the main
      driving force for citrate uptake. The rate of citrate uptake, driven by
      artificially imposed ion-gradients, is high in the presence of an artificial
      delta pH and low in the presence of an artificial delta psi. Citrate transport
      does not depend on the presence of Na+ or Mg2+ as has been observed for other
      citrate-transport systems. Citrate has three pK values: 3.14, 4.77 and 5.40.
      Citrate forms a stable complex with Mg2+ with a stability constant of 3.2.
      Kinetic parameters and calculations of the different citrate (Cit) species at a
      given pH, indicate that the HCit2- is the species transported and that transport
      occurs in symport with three protons. This citrate-transport system is thus a
      unique example of a 3H solute symport system.

PMID- 1991479
TI  - On the mechanism of sodium ion translocation by methylmalonyl-CoA decarboxylase
      from Veillonella alcalescens.
AB  - Veillonella alcalescens during lactate degradation developed an Na+ concentration
      gradient with 7-8 times higher external than internal Na+ concentrations in the
      logarithmic growth phase. The gradient declined to a factor of 1.9 in the late
      stationary phase. Methylmalonyl-CoA decarboxylase reconstituted into
      proteoliposomes performed an active electrogenic Na+ transport, creating delta
      psi of 60 mV, delta pNa+ of 50 mV, and delta mu Na+ of 110 mV. In the initial
      phase of the transport, the decarboxylase catalyzed the uptake of 2 Na+ ions
      malonyl-CoA molecule decarboxylated. During further development of the
      electrochemical Na+ gradient, this ratio gradually declined to zero, when
      decarboxylation continued without further increase of the internal Na+
      concentration. The rate of malonyl-CoA decarboxylation declined initially during
      development of the membrane potential, but remained unchanged later on. Monensin
      abolished the Na+ gradient and increased the malonyl-CoA decarboxylation rate 2.8
      fold. On dissipating the membrane potential with valinomycin, the internal Na+
      concentration reached three times higher values than in its absence, and the
      decarboxylation rate increased 2.8-fold. Methylmalonyl-CoA decarboxylase
      catalyzed an exchange of internal and external Na+ ions in addition to net Na+
      accumulation. The initial rate of Na+ influx was double that of malonyl-CoA
      decarboxylation. In the following, both rates decreased about twofold in parallel
      to values which remained constant during further development of the
      electrochemical Na+ gradient. Thus, Na+ influx and malonyl-CoA decarboxylation
      follow a stoichiometry of approximately 2:1, independent of the magnitude of the
      electrochemical Na+ gradient and are thus highly coupled events.

PMID- 1991480
TI  - Phosphorus-31 nuclear magnetic resonance of C6 glioma cells and rat astrocytes.
      Evidence for a modification of the longitudinal relaxation time of ATP and Pi
      during glucose starvation.
AB  - 31P-NMR spectroscopy has been used to study the energy metabolism and the NMR
      visibility of ATP and intracellular Pi of the C6 glioma cell line and rat
      astrocyte grown on microcarrier beads with the following results. 1. In vivo NMR
      spectra of C6 glioma cells and rat astrocytes indicate that these cells were able
      to maintain their level of ATP resonances during a long anoxic period (more than
      an hour). Both cell types were sensitive to ischemia which induced a loss of ATP
      resonances within 40 min. Glucose starvation induced by 40% decrease in ATP
      resonances correlated to a 50% increase in the intensity of the Pi signal. These
      changes corresponded to a new steady state which could be reversed by reperfusing
      the cells with a glucose-containing medium. 2. In contrast to in vivo data, 31P
      NMR analyses of perchloric acid extracts of cells incubated in a glucose-free
      medium showed that their ATP and Pi contents were unchanged during starvation.
      The changes of NMR visibility of the metabolites in living C6 cells were
      correlated to modifications of their macroscopic longitudinal relaxation times,
      evolving from 0.30 +/- 0.08 s and 6.6 +/- 1.5 s in the presence of glucose to
      0.68 +/- 0.26 s and 3.2 +/- 0.9 s in the absence of glucose for ATP and Pi,
      respectively. The changes of the NMR detectability of ATP and Pi indicate that
      changes in their microenvironment occur during glucose starvation, suggesting the
      existence of different pools of these metabolites within the cells. 3. Under
      various experimental conditions, i.e. anoxia, ischemia and glucose starvation,
      rat astrocytes in primary culture showed a very similar behavior to that of C6
      cells, suggesting a similar adaptability to the nature of the energy supply for
      both the normal and the malignant cell.

PMID- 1991481
TI  - Metabolism of [2-13C]succinate in renal cells determined by 13C NMR.
AB  - [2-13C]Succinate has been used to examine the metabolic carbon flux from the
      Krebs cycle in rat renal proximal convoluted tubular (PCT) cells under
      physiological and pathophysiological conditions. Therefore, we developed a
      mathematical model that enabled us to determine the metabolic fluxes of the Krebs
      cycle. A mathematical model for the calculation of flux from [2-13C]succinate was
      used to determine fluxes in rat PCT cells during chronic acidosis in the presence
      and absence of 0.1 mM angiotensin II. The relative carbon efflux via glutamate
      dehydrogenase in rat renal PCT cells increases during chronic acidosis from 0.27
      to 0.39, whereas this carbon flux is not affected by the presence of peptide
      hormone angiotensin II in the incubation medium. The fraction of intermediate 13C
      labelled oxaloacetate transformed into the phosphoenolpyruvate and aspartate
      pools increases significantly from 0.41 to 0.57 in the case of chronic acidosis.
      The carbon efflux is not affected by angiotensin II. The 13C-NMR data also show
      that the carbon efflux through phosphoenolpyruvate carboxykinase increases from
      0.35 to 0.56 in rat renal PCT cells derived from chronic acidotic animals, as
      well as in the presence of angiotensin II. The present results indicate that
      angiotensin II affects only the flux through phosphoenolcarboxykinase, whereas
      chronic acidosis increases the flux through phosphoenolpyruvate carboxykinase as
      well as the gluconeogenic flux.

PMID- 1991482
TI  - Thymus colonization in the developing mouse embryo.
AB  - We have directly followed the formation of and the thymus colonization by pro-T
      lymphocytes in the developing C57BL/6 mouse embryo by using the monoclonal
      antibody JORO 37-5 specific for pro-T lymphocytes, immunofluorescence staining
      and flow fluorocytometry or microscopy analysis. The results show that JORO 37-5+
      cells begin to appear in the liver at day 9 of gestation. These JORO 37-5+ cells
      migrate to and colonize the thymus 1 day later, where they expand vigorously
      during the next 4-5 days and, subsequently, switch off expression of JORO 37-5 as
      they further differentiate into mature thymocytes.

PMID- 1991483
TI  - Proliferative responses induced by the activation of protein kinase C during the
      development of human T lymphocytes.
AB  - We have studied the effects of phorbol-dibutyrate (PBu2), a protein kinase C
      (PKC) activator, on the proliferation of peripheral human T cells and thymocyte
      subpopulations selected by treatment with monoclonal antibodies and complement:
      pre-thymocytes (CD1a-CD3-CD4-CD8-), cortical thymocytes (CD3-, class I- antigens)
      and medullary thymocytes (enriched as CD1a- cells). PBu2 induces a dose-dependent
      proliferative response in human peripheral blood T cells at concentrations
      greater than 6 ng/ml, this proliferation being mediated by the autocrine
      interleukin 2 (IL2)/IL2 receptor (IL2R) pathway. Pre-thymocytes respond to PBu2
      in a way similar to T cells, being able to secrete IL2 in significant amounts and
      express the p55 chain of IL2R. On the other hand, cortical thymocytes are not
      induced to proliferate after PKC activation and neither expression of the p55
      chain of IL2R nor IL2 secretion is observed. Human medullary thymocytes,
      phenotypically identical to peripheral blood T cells, show no proliferation in
      response to PBu2 at any concentration tested unless IL2 is supplied to the
      cultures. The activation of PKC induces the expression of IL2R in these cells,
      but not IL2 secretion. The implications of PKC activation in thymic maturation,
      the role of IL2 and the relevance of the differences between medullary thymocytes
      and peripheral blood T cells are discussed.

PMID- 1991484
TI  - Nerve growth factor specifically induces human IgG4 production.
AB  - The effect of nerve growth factor (NGF) on human IgG4 production was studied. NGF
      specifically enhanced IgG4 production in cultures of human tonsillar mononuclear
      cells without affecting production of other isotypes or other IgG subclasses.
      Optimal enhancement of IgG4 production by NGF required the presence of T cells.
      However, NGF induced significant IgG4 production by small resting B cells in the
      absence of T cells, and this production was enhanced by stimulation with
      Staphylococcus aureus Cowan strain I (SAC). In contrast to small B cells, large
      activated B cells produced IgG4 spontaneously; this production was enhanced by
      NGF. NGF also enhanced IgM and IgA production by large B cells, while production
      of IgG1, IgG2, IgG3 and IgE was not affected. The enhancement of IgG4 production
      was blocked by anti-NGF serum but not by control serum. NGF, T cells and SAC,
      separately or together, failed to induce IgG4 production by surface (sIgG4+)
      depleted B cells. In contrast to NGF, other recombinant human cytokines including
      interleukin (IL) 1 beta, IL 2, IL 4, IL 5, IL 6, granulocyte-macrophage colony
      stimulating factor, interferon alpha and gamma failed to induce IgG4 production.
      These results suggest that NGF directly and preferentially stimulates activated
      sIgG4+ B cells to produce IgG4.

PMID- 1991485
TI  - Cell-type-specific recognition of allogeneic cells by alloreactive cytotoxic T
      cells: a consequence of peptide-dependent allorecognition.
AB  - Recently, we provided the first direct evidence that the determinant recognized
      by some alloreactive cytotoxic T lymphocytes (CTL) clones included an endogenous
      peptide antigen(s), which could be derived by cyanogen bromide cleavage of
      cytoplasmic proteins. The studies outlined in this report provide three important
      findings which confirm and extend our previous results. First, the description of
      peptide-dependent Kb-specific alloreactive CTL clones is now extended to clones
      isolated from several responders primed with allogeneic EL4 tumor cells. This
      indicates that the previously reported results were not unique to the original
      EL4-primed responder. Second, we establish that peptide-dependent Kb-specific
      alloreactive CTL clones can be identified after priming with normal allogeneic
      spleen cells. Thus, induction of peptide-dependent CTL clones is not a unique
      property of EL4 tumor cells. These results suggest that peptide plays an
      important role in formation of the allogeneic determinants recognized during
      graft rejection. Third, these studies reveal that a number of alloreactive CTL
      clones exhibit cell-type-specific recognition of allogeneic murine target cells.
      This is consistent with the possibility that some CTL clones recognize peptide
      antigens that are limited in their tissue distribution. The mechanisms and
      implications of these findings are discussed.

PMID- 1991486
TI  - Morphological features of cloned lymphocytes expressing gamma/delta T cell
      receptors.
AB  - We have analyzed the morphological characteristics of human T lymphocytes bearing
      CD3-associated T cell receptor (TcR) gamma and delta chains. BB3 and delta-TCS1
      monoclonal antibodies (mAb) were used to identify two distinct, nonoverlapping
      populations of TcR gamma/delta + cells which express the products of V delta 2
      and V delta 1 gene segments, respectively. In the peripheral blood, most V delta
      1+ (delta TCS-1+) lymphocytes express the non-disulfide-linked form of receptor
      whereas V delta 2+ (BB3+) cells express the disulfide-linked form. The majority
      of cloned TcR gamma/delta + cells exhibit a growth pattern different from that of
      conventional TcR alpha/beta + cells as they adhere promptly to surfaces and
      undergo morphological changes which can be summarized as follows: cells spread on
      the surface, form a distinct uropod and, in the final phase of adherence, emit
      long filopodia ending with adhesion plaques. Immunofluorescence studies of TcR
      gamma/delta + clones demonstrated the presence of submembraneous actin
      microfilaments and actin-binding protein confirming that these cells are capable
      of active motility which is related to the propensity of TcR gamma/delta + cells
      to home to epithelia. Scanning electron microscope analyses of effector/target
      cell conjugates showed that in TcR gamma/delta + cells the region of the uropodia
      next to the cell body is responsible for the binding to tumor target cells.
      Interestingly, immunofluorescence analyses revealed that LFA-1 molecules are
      predominantly distributed in the uropodium whereas they are virtually absent in
      the cell bodies. These morphological characteristics of TcR gamma/delta + cells
      may pertain to defensive mechanisms the mucosal level.

PMID- 1991487
TI  - L-arginine-dependent destruction of intrahepatic malaria parasites in response to
      tumor necrosis factor and/or interleukin 6 stimulation.
AB  - There is growing evidence that cytokines (interleukin [IL] 1, IL 6, interferon
      gamma, tumor necrosis factor [TNF]) directly or indirectly interfere with the
      intrahepatic development of malaria parasites. Recent work in our laboratory
      clearly showed that TNF can affect the hepatic development of parasites via IL 6
      secreted by liver nonparenchymal cells. The possible participation of an L
      arginine-dependent effector mechanism has been studied to explain the TNF/IL 6
      induced inhibition. We thus investigated if NGmonomethyl-L-arginine and N omega
      nitro-L-arginine, two specific inhibitors of inorganic nitrogen oxide synthesis
      from L-arginine, were able to affect the inhibitory effect of TNF and/or IL 6 in
      co-cultures. At 0.1 and 0.5 mM both L-arginine analogues reversed the inhibitory
      effect of these cytokines. An interesting observation is that L-arginine
      analogues enhance schizont development in the absence of prior cytokine contact.
      This result indicates an hepatic basal L-arginine-dependent anti-parasitic
      activity which might explain the existence of self-degenerating hepatic forms as
      previously reported.

PMID- 1991488
TI  - Specific suppression of antibody responses by soluble protein-specific, class II
      restricted cytolytic T lymphocyte clones.
AB  - Antigenic stimulation with exogenous soluble proteins induces cytotoxic T
      lymphocytes (CTL) recognizing antigenic peptides presented on class II major
      histocompatibility complex (MHC) molecules. Such CTL have been shown to lyse
      preferentially B cells expressing immunoglobulin receptors reactive with the
      relevant antigens, presumably because such B cells can efficiently trap and
      present the antigen. Therefore, possible involvement of soluble protein antigen
      specific CTL in specific suppression of antibody responses has been hypothesised.
      In this report, keyhole limpet hemocyanin and ovalbumin-specific, class II
      restricted CD4+ CTL clones established from lymph nodes of immunized mice were
      examined for their suppressive activities on antibody production. When these CTL
      clones were added to in vitro secondary cultures, genetically restricted, carrier
      specific suppression of anti-2,4,6-trinitrophenyl antibody production was
      observed. These data therefore demonstrate that CTL directed toward soluble
      antigens are capable of mediating specific suppression of antibody responses.
      Furthermore, the antibody response of MHC-heterozygous F1 lymphocytes was almost
      completely suppressed by a CTL clone restricted to one parental class II MHC
      antigen, indicating that the mechanism of suppression by these CTL is distinct
      from that by classical suppressor T cells.

PMID- 1991489
TI  - Dividing cells in bone marrow and spleen incorporate bromodeoxyuridine with high
      efficiency.
AB  - Labeling of dividing cells with the thymidine analogue 5-bromo-2'-deoxyuridine
      (BrdUrd) has been frequently used to determine the life-span of cells in various
      lymphocyte subsets. In this study we address the question of whether
      administration of BrdUrd in vivo allows labeling of proliferating lymphocytes at
      early as well as later stages of maturation with high efficiency. For this
      purpose, the proportion of BrdUrd-labeled cells among all cells synthesizing DNA
      was determined in the bone marrow and spleen of mice that had received a single
      injection of BrdUrd or, alternatively, had been fed with BrdUrd for 1 week. On
      the average, 87% of bone marrow and 83% of spleen cells in the S phase of the
      cell cycle, as determined by DNA content, were labeled with BrdUrd 1.5 h
      following injection of the drug. We conclude from these data that administration
      of BrdUrd in vivo allows labeling of the vast majority of the dividing cells in
      both primary and secondary lymphoid organs and thus represents an efficient
      method to determine the life-span of lymphoid cells in vivo.

PMID- 1991490
TI  - Allelic exclusion of membrane but not secreted immunoglobulin in a mature B cell
      line.
AB  - Although many B lymphocytes contain two completely rearranged immunoglobulin (Ig)
      heavy (H) chain genes, only one of the alleles specifies a protein product. This
      phenomenon is termed allelic exclusion and is controlled in part by the membrane
      portion of Ig H chains. We have identified a mature B cell line derived from
      murine bone marrow that expresses two H chain proteins, gamma 3 and gamma 2b.
      Proteins of appropriate size for the membrane and secreted forms of both H chains
      are produced and both IgG3 and IgG2b are secreted from the cells. However, only
      IgG3 is expressed on the membrane. Detailed restriction mapping of the H chain
      genes indicates that both are rearranged, one containing a VHJ558 gene linked to
      the gamma 3 constant region and the other a VHS107 gene linked to the gamma 2b
      constant region. Primer extension sequencing of the RNA reveals that the gamma 2b
      RNA is transcribed from the allele containing VHS107 sequences while the gamma 3
      RNA is transcribed from the allele containing VHJ558 sequences. Thus, this mature
      B cell line secretes two distinct antibody molecules but is allelically excluded
      at the level of surface Ig expression. This cell line provides a model system to
      study factors, in addition to aberrant rearrangement, that influence allelic
      exclusion.

PMID- 1991492
TI  - Doxorubicin toxicity in relation to the proliferative state of human
      hematopoietic cells.
AB  - The relation between the proliferative state of normal human hematopoietic cells
      and their sensitivity to doxorubicin was studied. T-lymphocytes were stimulated
      with phytohaemagglutinin/interleukin 2 before or after a 2-h exposure to
      doxorubicin (range 0-2 microgram/ml). The doxorubicin concentration that
      inhibited DNA synthesis in 50% of the lymphocytes, measured qualitatively with 5
      iodo-2'-deoxyuridine incorporation, was significantly lower (a factor of 2.5) in
      case of drug exposure of stimulated lymphocytes compared to nonstimulated
      lymphocytes. These proliferation-dependent differences were not related to
      differences in cellular drug concentrations, as was determined with flow
      cytometry. Bone marrow cells were stimulated for 2 days with human placenta
      conditioned medium before or after exposure to doxorubicin (range 0-2
      microgram/ml), after which they were cultured in a bone marrow clonogenic assay.
      In analogy with the lymphocyte experiments, proliferation-dependent differences
      in drug sensitivity were found. The drug concentration that inhibited the growth
      of granulocyte-macrophage colonies (granulocyte-macrophage colony-forming units,
      CFU-GM) to 50% appeared significantly lower (a factor of 3.4) with drug exposure
      of stimulated bone marrow cells compared to nonstimulated bone marrow cells. The
      relative insensitivity of quiescent, but potentially proliferative cells to
      doxorubicin might explain the recovery of hematopoiesis after doxorubicin-induced
      bone marrow hypoplasia.

PMID- 1991491
TI  - Negative regulators of in vivo erythropoiesis: interaction of IL-1 alpha and TNF
      alpha and the lack of a strict requirement for T or NK cells for their activity.
AB  - The macrophage-derived cytokines interleukin 1 alpha (IL-1 alpha) and tumor
      necrosis factor-alpha (TNF-alpha) have significant effects on hematopoiesis in
      vitro and in vivo. Studies in our laboratory have demonstrated that, in vivo, IL
      1 alpha and TNF-alpha suppress late stage erythropoiesis while stimulating the
      macrophage-granulocyte lineage. In the present studies, we have examined the
      mechanisms of these effects. Normal mice were treated with a single dose of
      either recombinant murine IL-1 alpha or TNF-alpha (1.25 x 10(6) or 10(5) U/mouse
      i.p., respectively) with or without pretreatment of the animals with monoclonal
      anti-murine TNF-alpha antibody at a dose that has been shown to be capable of
      abrogating endogenous TNF activity induced by lipopolysaccharide (LPS). After 5
      days, effects on late-stage erythropoiesis and macrophage formation were measured
      by determining the number of their progenitors, erythroid colony-forming units
      (CFU-E) and macrophage colony-forming units (CFU-M), in the spleen. Anti-TNF
      alpha antibody treatment significantly abrogated CFU-E suppression by IL-1 alpha
      but had no effect on the IL-1 alpha-induced stimulation of CFU-M. IL-1 alpha and
      TNF-alpha suppressed CFU-E in vivo and stimulated CFU-M in the spleens of T-cell-
      and natural killer (NK)-cell-deficient mice. Neither cytokine suppressed CFU-E
      colony formation in vitro. These results demonstrate that IL-1 alpha-induced
      suppression of CFU-E is mediated through induction of TNF-alpha, IL-1 alpha
      stimulation of CFU-M was independent of TNF-alpha, and the in vivo hematopoietic
      effects of these cytokines do not strictly require intact T- and NK-cell function
      for activity.

PMID- 1991493
TI  - Stromal cells in long-term cultures of liver, spleen, and bone marrow at
      different developmental ages have different capacities to maintain GM-CFC
      proliferation.
AB  - Measurements were made of the granulocyte-macrophage colony-forming cell (GM-CFC)
      yield in long-term cultures established from different combinations of stroma and
      hemopoietic recharge inocula derived from hemopoietic organs at different stages
      of their embryological development. Results indicated differences in the
      supporting capacity of the stroma, related to the hemopoietic activity of the
      organ of origin. Stroma derived from hemopoietically active organs (adult bone
      marrow, neonatal spleen, fetal liver) supported the proliferation of GM-CFC to a
      larger extent than stroma derived from organs with a low hemopoietic activity
      (neonatal bone marrow liver at 2 days; spleen at 3 weeks). Regardless of the
      origin of the hemopoietic cells, stroma from adult bone marrow displayed the
      highest ability to support GM-CFC proliferation. The capacity of GM-CFC from
      hemopoietic recharge cell populations to proliferate on stroma was not related to
      the hemopoietic activity of their organ of origin. Regardless of their organ of
      origin the GM-CFC present in each of the different hemopoietic recharge
      populations were able to proliferate provided that they were seeded on an
      appropriate stroma. These experiments showed that stromal cells cultured from
      hemopoietic organs at different developmental ages determine the hemopoietic
      activity of long-term cultures as measured via GM-CFC recovery.

PMID- 1991494
TI  - Effect of lipopolysaccharide on the production of colony-stimulating factors by
      the stromal cells in long-term bone marrow culture.
AB  - The production of colony-stimulating factors (CSFs) by murine bone marrow stromal
      cells was studied with Dexter long-term bone marrow culture (LTBMC). For
      induction of CSF release, various concentrations (0.5-40.0 microgram/ml) of
      bacterial lipopolysaccharide (LPS) were added to nonrecharged 3-week-old LTBMCs
      consisting of an intact or macrophage-depleted adherent cell layer. The depletion
      of monocytes/macrophages from freshly prepared bone marrow cell suspension was
      performed by carbonyl-iron incorporation before establishment of LTBMC. The
      supernatants (Sup) of normal LTBMCs contained a low level of macrophage colony
      stimulating factor (M-CSF) that was produced by the adherent cells but not by the
      nonadherent cell elements. No colony inhibitor was found in the Sup of LTBMCs,
      whereas a colony-promoting activity (CPA) was detected in medium conditioned by
      the adherent marrow cells (AC-CM). CPA could enhance the colony formation of
      myeloid progenitor cells when used in combination with recombinant murine
      granulocyte-macrophage colony-stimulating factor (GM-CSF). The production of CSFs
      peaked at about 24 h after refeeding, but it then declined to only half the
      optimal activity at the end of the week. Addition of LPS to the intact LTBMC
      invariably increased the production of a GM-CSF-like cytokine. The release of
      this cytokine was dose dependent and peaked at a dosage of 20 micrograms/ml of
      LPS at 24 h after treatment. In contrast, macrophage-depleted marrow-adherent
      cells failed to respond to LPS for CSF secretion. These results suggest that LPS
      can stimulate marrow macrophages to directly release CSF or to potentiate the
      production of CSF by other stromal cells.

PMID- 1991495
TI  - Purification of an in vitro inhibitor of normal myelopoiesis using a monoclonal
      antibody directed to a common antigen of myelogenous leukemia (CAMAL).
AB  - A monoclonal antibody, CAMAL-1, has been previously shown to react specifically
      and at high frequencies with cells of patients with acute myelogenous leukemia
      (AML) and chronic granulocytic leukemia (CGL). High expression of this antigen in
      remission patients' bone marrow cells was shown to correlate with both relapse
      and lower survival times. Preliminary studies showed that material extracted from
      leukemic cells and eluted from CAMAL-1 immunoadsorbent columns profoundly
      inhibited the formation of normal colony-forming units (CFU) but had no effect on
      formation of such colonies from cells of patients with CGL. We have used CAMAL-1
      affinity chromatography in combination with FPLC gel filtration to purify the
      inhibitory material from leukemic cell extracts. We have successfully isolated a
      30-kd component (P30) that functions as an inhibitor of normal myelopoiesis in
      vitro; when P30 was added to normal progenitor cell assays it significantly
      inhibited the growth of normal CFU but had no inhibitory effect on the growth of
      CGL progenitor cells at equivalent concentrations. The inhibitory effect is
      preferentially directed to granulocytic progenitors. Antibodies raised to P30
      reacted in Western blot analyses with affinity purified material from patients'
      cells as well as with a 30-kd component in the cell lysates and supernatants of
      the leukemic cell lines HL60 and K562; this finding suggested that the P30
      inhibitory component might be produced by leukemic cells.

PMID- 1991496
TI  - Single high doses of cyclophosphamide enable the collection of high numbers of
      hemopoietic stem cells from the peripheral blood.

PMID- 1991497
TI  - Hepatic eosinophilopoiesis from multipotent hemopoietic stem cells in Toxocara
      canis-infected mice.
AB  - Extramedullary hemopoiesis, recognized as hemopoietic foci, increased in the
      livers of Toxocara canis-infected mice. At the peak of the response (day-13 after
      infection), the majority of hepatic hemopoietic foci were of the eosinophil
      lineage. Hepatic nonparenchymal cells prepared from T. canis-infected mice on day
      13 contained large numbers of hemopoietic stem cells, more than half of which
      were cycling. When W/Wv mice, which are genetically deficient in multipotent
      hemopoietic stem cells, were infected with T. canis, hepatic hemopoietic foci
      were rare throughout the course of infection. This impaired response of W/Wv mice
      was restored by bone marrow grafting from normal +/+ littermates. These results
      indicate that, in response to the increased demand, eosinophils are generated in
      the liver by the differentiation from multipotent stem cells, not only from the
      committed precursors.

PMID- 1991498
TI  - Recovery of the proliferative and functional integrity of mouse bone marrow in
      long-term cultures established after whole-body irradiation at different doses
      and dose rates.
AB  - Injury inflicted upon the bone marrow stroma following whole-body irradiation and
      its repair over a 1-year period has been assessed in murine long-term bone marrow
      cultures established at increasing time intervals after irradiation. Different
      doses at different dose rates (10 Gy at 0.05 cGy/min, 4.5 Gy and 10 Gy at 1.6
      cGy/min, and 4 x 4.5 Gy [3 weeks between doses] at 60 cGy/min) were chosen so as
      to maximize differences in effect in the stroma. The cellularity of the adherent
      layer in long-term cultures established 1 month after irradiation was reduced by
      40%-90% depending on the dose and dose rate. Simultaneous with the poor ability
      of the marrow to form adherent layers, the cumulative spleen colony-forming unit
      (CFU-S) and granulocyte-macrophage colony-forming cell (GM-CFC) production over a
      7-week period was reduced to 0% and 30% of control cultures, respectively. The
      slow recovery of the adherent layer was paralleled by an increase in the numbers
      of CFU-S and GM-CFC in the supernatant. Cultures established from repeatedly
      irradiated mice performed poorly over the entire 1-year period. Whereas the
      regeneration of the stroma was near complete 1 year after irradiation, the CFU-S
      and GM-CFC levels reached only between 50% and 80% of control cultures,
      respectively. Also, the concentration of CFU-S and GM-CFC in the supernatant
      remained persistently lower in cultures established from irradiated mice as
      compared to control cultures. The levels of sulfated glycosaminoglycans, which
      have been implicated in the establishment of the functional integrity of the
      microenvironment, were not reduced in the adherent layers at any time after
      irradiation. These results indicate that the regeneration of the stroma is
      accompanied by an incomplete recovery of active hemopoiesis in vitro. However, no
      evidence was found for persistent functional defects in the stroma after
      irradiation, using the present endpoints.

PMID- 1991499
TI  - Developmental changes in human megakaryocyte ploidy.
AB  - Megakaryocytes (MK) obtained from the differentiation of MK colony-forming units
      (CFU-MK) were grown from fetal liver, cord blood, and adult marrow in liquid
      culture containing aplastic plasma. Ploidy distribution was studied by a double
      staining technique and flow cytometry and MK maturation by ultrastructural
      techniques. Cultured MK from fetuses and neonates were small sized (about 10
      microns) in comparison to adult MK. They were mature cells that contained large
      membrane complexes as previously found in vivo. Only 2N and 4N MK were usually
      present in 8- to 10-week-old fetus cultures; 8N MK were detected at 20 weeks of
      gestation and in neonates. Higher ploidy classes were present in culture from
      adults but with a much lower frequency than in marrow. Therefore, a progressive
      shift to higher ploidy and an increase in MK size were observed simultaneously
      during development. Interleukin 3 (IL-3) increased MK proliferation as in adults
      but abrogated MK ploidization of 20-week-old fetus culture. The present results
      suggest that the changes occurring during ontogenesis are related to intrinsic MK
      modifications because no inhibitor of MK ploidization could be detected in fetal
      cultures.

PMID- 1991500
TI  - An improved negative immunomagnetic selection strategy for the purification of
      primitive hemopoietic cells from normal bone marrow.
AB  - An improved negative immunomagnetic selection strategy has been devised for the
      enrichment of primitive hemopoietic cells using the high proliferative potential
      colony-forming cell (HPP-CFC) assay as an index of stem cell purification.
      Immunomagnetic selection was carried out using goat anti-rat conjugated M-450
      Dynabeads and a cocktail of rat monoclonal antibodies directed against lineage
      antigens expressed on B-lymphocytes (B220), neutrophils and activated macrophages
      (7/4), differentiating erythroid cells (YW 25.12.7), and T-lymphocyte subsets
      (Lyt-2 and L3T4). This negative selection strategy results in the highly
      reproducible enrichment of HPP-CFC with negligible loss of HPP-CFC at the
      immunomagnetic selection step. A 30-fold enrichment of HPP-CFC stimulated by
      interleukin 3 (IL-3) plus colony-stimulating factor (CSF-1), or interleukin 1
      alpha (IL-1 alpha) plus IL-3 plus CSF-1, is obtained with simultaneous resolution
      of HPP-CFC from progenitor cells of low proliferative potential responsive to CSF
      1 alone (LPP-CFC). Flow cytometric analysis of these lineage-negative cells
      reveals that they almost exclusively exhibit the light-scattering characteristics
      of blast cells and the morphology of a candidate hemopoietic stem cell. Positive
      fluorescence-activated cell sorting of immunomagnetically pre-enriched normal
      bone marrow cells using wheat germ agglutinin yields cell preparations with a
      cloning efficiency of up to 45% and a HPP-CFC content of 20%.

PMID- 1991501
TI  - Where is the glycolytic complex? A critical evaluation of present data from
      muscle tissue.
AB  - Associations between glycolytic enzymes and subcellular structures have been
      interpreted as presenting a novel mechanism of glycolytic control; reversible
      enzyme binding to subcellular structural components is believed to regulate
      enzyme activity in vivo through the formation of a multi-enzyme complex. However,
      three lines of evidence suggest that enzyme binding to cellular structures is not
      involved in the control of glycolysis. (i) Calculations of the distribution of
      glycolytic enzymes under the physiological cellular conditions of higher ionic
      strength and higher enzyme concentrations indicate that a large multi-enzyme
      complex would not exist. (ii) In many cases, binding to subcellular structures is
      accompanied by changes in enzyme kinetic parameters brought about by allosteric
      modification, but these changes often inhibit enzyme activity. (iii) In the case
      where formation of binary enzyme/enzyme complexes activates enzymes, the overall
      increase in flux through the enzyme reaction is negligible.

PMID- 1991502
TI  - Inhibition of digestive proteinases of stored grain Coleoptera by oryzacystatin,
      a cysteine proteinase inhibitor from rice seed.
AB  - Electrophoresis of midgut extracts from the rice weevil, Sitophilus oryzae, and
      the red flour beetle, Tribolium castaneum, in polyacrylamide gels containing
      sodium dodecyl sulfate and gelatin revealed there was one major proteinase
      (apparent molecular mass = 40,000) in the rice weevil and two major proteinases
      (apparent molecular masses = 20,000 and 17,000) in the red flour beetle. The pH
      optima using [3H]casein as substrate were about pH 6.8 for the rice weevil and pH
      5.2 for the red flour beetle. Use of specific inhibitors, including L-trans
      epoxysuccinyl-leucylamino-(4- guanidino)-butane (E-64), p
      chloromercuriphenylsulfonic acid (PCMS), and oryzacystatin, indicated that nearly
      all of the proteinase activity against casein was contributed by cysteine
      proteinases. The estimated IC50 values for oryzacystatin were 2 x 10(-6) M and 4
      x 10(-7) M when tested against midgut extracts from T. castaneum and S. oryzae,
      respectively.

PMID- 1991503
TI  - Regulation of the catalytic activity and oligomeric composition of enzymes in
      reversed micelles of surfactants in organic solvents.
AB  - The phenomenon of regulation of the catalytic activity of enzymes via changing
      their oligomeric composition in the system of reversed micelles of sodium bis(2
      ethylhexyl)sulfosuccinate (AOT) in octane was studied using alpha-chymotrypsin
      (CT) from bovine brain and alkaline phosphatase (AP) from calf intestinal mucosa.
      The dependences of the enzyme catalytic activity on the AOT hydration degree (Wo
      = [H2O]/[AOT]), the parameter determining the radius (rc) of the inner cavity of
      micelles, usually represent the bell-shaped curves. The maximal catalytic
      activity is observed at such Wo when rc is equal to the size of the enzyme
      molecule. The position of this maximum strictly correlates with the enzyme
      oligomeric composition. Thus, in the case of CT this is observed at Wo = 12 when
      rc is equal to the radius (rp) of the CT globule. In the case of artificially
      produced conjugate containing six cross-linked CT molecules, this is observed at
      Wo = 43 when rc is equal to the radius of the sphere surrounding the absolute
      octahedron composed of six CT globules. The dependence of the catalytic activity
      of AP on Wo represents a curve with two maxima that are observed when rc is equal
      to rp of either AP monomer (Wo = 17) or AP dimer (Wo = 25). Ultracentrifugation
      experiments revealed that variation of Wo causes a change in the oligomeric
      composition of AP - its transition from monomeric (Wo less than 20) to dimeric
      form (Wo greater than 20). Hence, the observed maxima correspond to functioning
      of different oligomeric forms of AP.

PMID- 1991504
TI  - Effect of alpha-ketoglutarate and its structural analogues on hysteretic
      properties of alpha-ketoglutarate dehydrogenase.
AB  - The burst of product accumulation during the KGD reaction was investigated. It
      has been shown not to be the obligatory feature of catalysis, but appears when
      increasing the enzyme saturation by KG. Structural analogues of KG and the SH
      group modification suppress the initial burst without preventing catalysis. The
      results obtained are in favour of the existence of the regulatory site for
      binding KG and its structural analogues essential for hysteretic properties of
      KGD.

PMID- 1991505
TI  - Identification of sulfurtransferase enzymes in Azotobacter vinelandii.
AB  - Rhodanese and 3-mercaptopyruvate sulphurtransferase have been identified in A.
      vinelandii. Two distinct active fractions of the two sulphur transferases were
      obtained after FPLC ion-exchange chromatography of material partially purified
      from crude extracts. Rhodanese has been purified to homogeneity, and it consists
      of one polypeptide chain of Mr ca 25,000. A partial purification of 3
      mercaptopyruvate sulphurtransferase was obtained.

PMID- 1991506
TI  - Solution structure of mu-conotoxin GIIIA analysed by 2D-NMR and distance geometry
      calculations.
AB  - We have investigated the structure of mu-conotoxin GIIIA by 2D-NMR methods. The
      assignment of 1H NMR spectra and a quantitative analysis of NOE and J-coupling
      data are presented. These results were used for the calculation of secondary
      structure elements of mu-conotoxin GIIIA. Distance geometry calculations were
      carried out to define the global folding of the peptide.

PMID- 1991507
TI  - Porcine pancreas extract decreases blood-ionized calcium in mice and inhibits
      osteoclast formation and bone resorption in culture.
AB  - Patients with acute pancreatitis commonly manifest hypocalcemia for reasons which
      are unknown. We found that porcine pancreas extracts (PX) significantly decreased
      blood-ionized calcium in Balb/c mice. Partially-purified PX with a molecular mass
      of approximately 27 kDa decreased blood-ionized calcium in the mice. Partially
      purified PX suppressed not only 45Ca release from fetal rat long bones which had
      been stimulated by parathyroid hormone, interleukin-1 alpha, tumor necrosis
      factor, transforming growth factor-alpha, 1,25-dihydroxyvitamin D3 and
      prostaglandin E2, but tartrate-resistant acid phosphatase-positive multinucleated
      cell formation in the presence of 1,25-dihydroxyvitamin D3 in mouse marrow
      cultures. The results suggest that there is an as yet-unidentified bone
      metabolism-regulating substance in porcine pancreas which might be responsible
      for the hypocalcemia associated with acute pancreatitis.

PMID- 1991508
TI  - Thimerosal causes calcium oscillations and sensitizes calcium-induced calcium
      release in unfertilized hamster eggs.
AB  - Calcium-induced-calcium-release (CICR) was assayed in unfertilized golden hamster
      eggs by injecting Ca2+ and monitoring Ca2(+)-dependent hyperpolarizing responses
      (HRs) and Ca2(+)-sensitive fluo-3 fluorescence. Incubating eggs in the sulfhydryl
      reagent thimerosal caused [Ca2+]i oscillations as monitored by Ca2(+)-dependent
      HRs and decreased approximately 10-fold the Ca2+ injection current required to
      generate an HR and cause a large intracellular Ca2+ increase. Thimerosal also
      enhanced the sensitivity of eggs to Ca2+ injection in a calcium-free medium. The
      effects of thimerosal on CICR were prevented by dithiothreitol and were not
      mimicked by injecting inositol 1,4,5-trisphosphate. The data suggest that
      thimerosal may be an alternative agent for studying CICR in caffeine-insensitive
      cells.

PMID- 1991509
TI  - Suicide process of renal cell carcinoma cells encountering mumps virus.
AB  - Renal cell carcinoma cells produced the substance(s) which killed them (suicide
      factor(s)) after co-culture with mumps virus. The suicide factor(s) were heat
      sensitive and were degraded with trypsin. Furthermore, actinomycin D inhibited
      the production of the substance(s) by cancer cells. Considering these facts, the
      substance(s) were thought to be protein(s) derived from de novo synthesis in
      cancer cells. It was demonstrated that renal cell carcinoma cells proliferated
      with the autocrine loop of interleukin-6 (IL-6). Mumps virus almost completely
      inhibited the IL-6 production in several hours. Because of these two facts, the
      suicide process might be initiated in renal cell carcinoma cells after
      encountering mumps virus, i.e. inhibition of the autocrine growth loop of IL-6
      followed by the induction of an autocrine killing loop of unknown substance(s).

PMID- 1991510
TI  - Biochemical evidence for histidine oxidation in photosystem II depleted of the Mn
      cluster for O2-evolution.
AB  - Flash excitation of Tris-treated photosystem II (PSII) membranes generated a
      thermoluminescence band peaking at -20 degrees C, indicating that a positively
      charged oxidizing equivalent is stably accumulated on donor side of PSII even in
      the absence of the Mn-cluster. This oxidizing equivalent was sensitive to low
      concentrations of exogenous Mn2+, and its stable accumulation was reversibly
      inhibited by diethylpyrocarbonate treatment that modifies histidine residues with
      high specificity. It was inferred that there is a photooxidizable histidine
      residue(s) on donor side of PSII and it provides a redox-active ligand for Mn.

PMID- 1991511
TI  - Human milk bile-salt stimulated lipase. Sequence similarity with rat
      lysophospholipase and homology with the active site region of cholinesterases.
AB  - To determine the active site residue, human milk bile-salt stimulated lipase
      (BSSL) was labelled with [3H]diisopropyl fluorophosphate (DFP). Partial sequence
      analysis of cyanogen bromide fragments (a total of 146 residues from 6 peptides)
      revealed 84% sequence identity with a putative rat lysophospholipase. Sequence
      analysis of a [3H]DFP-labelled peptide indicated that the active site serine was
      contained in the sequence Gly-Glu-Ser-Ala-Gly. In addition to similarity with rat
      lysophospholipase, this sequence showed homology with regions of human
      butyrylcholinesterase and electric ray acetylcholinesterase (68% identity). It is
      concluded that these proteins are members of a new supergene family.

PMID- 1991512
TI  - Cloning and expression of cDNA encoding 25-hydroxyvitamin D3 24-hydroxylase.
AB  - A cDNA encoding 25-hydroxyvitamin D3 24-hydroxylase (P450cc24) was isolated from
      a rat kidney cDNA library using specific antibodies to the enzyme. The isolated
      cDNA was 3.2 kbp long and contained a 1542-bp open reading frame encoding 514
      amino acids. The deduced amino acid sequence contained a presequence typical of
      mitochondrial enzymes in the N-terminal region. The amino acid sequence shows
      less than 30% similarity to those of any other cytochrome P450s so far reported
      and, therefore, P450cc24 constitutes a novel family of P450. COS-7 cells
      transfected with the cDNA produced a protein that was reactive with the
      antibodies and catalyzed NADPH-dependent 24-hydroxylation of 25-hydroxyvitamin D3
      in the presence of adrenodoxin and NADPH-adrenodoxin reductase. Using the cDNA as
      a probe we demonstrated that the increase of 24-hydroxylation activity caused by
      administration of vitamin D3 into rats was accompanied by an increase of the
      mRNA.

PMID- 1991513
TI  - Non-viral cellular substrates for human immunodeficiency virus type 1 protease.
AB  - A computer search revealed 10 proteins with homology to the sequence we
      originally identified in vimentin as the site of cleavage by human
      immunodeficiency virus type 1 (HIV-1) protease. Of these 10 proteins (actin,
      alpha-actinin, spectrin, tropomyosins, vinculin, dystrophin, MAP-2, villin, TRK-1
      and Ig mu-chain), we show that 4 of the first 5 were cleaved in vitro by this
      protease, as are MAP-1 and -2 [(1990) J. Gen. Virol. 71, 1985-1991]. In these
      proteins, cleavage is not restricted to a single motif, but occurs at many sites.
      However, cleavage is not random, since 9 other proteins including the
      cytoskeletal proteins filamin and band 4.1 are not cleaved in the in vitro assay.
      Thus, the ability of HIV-1 protease to cleave specific components of the
      cytoskeleton may be an important, although as yet unevaluated aspect of the life
      cycle of this retrovirus and/or may directly contribute to the pathogenesis
      observed during infection.

PMID- 1991514
TI  - Stopped-flow fluorescence kinetic studies of Glu-plasminogen. Conformational
      changes triggered by AH-site ligand binding.
AB  - Binding of 6-aminohexanoic acid to the AH-site, a weak lysine binding site in Glu
      plasminogen, alters the conformation of the molecule. The kinetics of the binding
      and the accompanying conformational change are investigated at pH 7.8, 25 degrees
      C. Changes of intrinsic protein fluorescence were measured as a function of time
      after rapid mixing in a stopped-flow apparatus. The results reflect a two-step
      reaction mechanism: Rapid association of Glu-plasminogen and 6-aminohexanoic acid
      (K1 = 44 mM) followed by the conformational change (k2 = 69 s-1 and k-2 = 3 s-1)
      with an overall dissociation constant Kd = 2.0 mM. Thus the conformational change
      is rather fast, t12 = 0.01 s. Its importance for the rates of Glu-plasminogen
      activation reactions is discussed.

PMID- 1991515
TI  - In vivo promoter activity of the synthetic Pribnow box.
AB  - The synthetic polydeoxyribonucleotides TGCA(TTATAATGCA)1-4, containing the
      consensus Pribnow box, were inserted upstream of the promoterless gal operon in a
      specially constructed plasmid. Using the MacConkey agar indicator technique it
      has been shown that these inserts are able to induce an efficient in vivo
      expression of the gal operon.

PMID- 1991516
TI  - Cloning and sequencing of the gene encoding the large (alpha-) subunit of the
      proteasome from Thermoplasma acidophilum.
AB  - The gene encoding the alpha-subunit of the proteasome from the archaebacterium
      Thermoplasma acidophilum was cloned and sequenced. The gene encodes for a
      polypeptide with 233 amino acid residues and a calculated molecular weight of
      25870. Sequence similarity of the alpha-subunit with the Saccharomyces cerevisiae
      wild-type suppressor gene scll+ encoded polypeptide, which is probably identical
      with the subunit YC7-alpha of the yeast proteasome, lends support to a putative
      role of proteasomes in the regulation of gene expression. The significant
      sequence similarity to the various subunits of eukaryotic proteasomes make it
      likely that proteasomal proteins are encoded by one gene family of ancient
      origin.

PMID- 1991517
TI  - Differential expression of the mouse D2 dopamine receptor isoforms.
AB  - We have identified and characterized the cDNAs corresponding to the mouse D2
      dopamine receptors. We show that in the mouse the D2 dopamine receptor is found
      in two forms, generated by alternative splicing of the same gene, mRNA
      distribution analysis of areas expressing the D2 receptors shows that the larger
      form is the most abundant, except in the brain stem where the shorter form is
      predominant. Membranes of mammalian cells transiently transfected with both forms
      of D2 receptor bind [3H]spiperone with a high affinity.

PMID- 1991518
TI  - Left handed alpha-helix formation by a bacterial peptide.
AB  - The alpha-helix is a common element of secondary structure in proteins and
      peptides. In eukaryotic organisms, which exclusively incorporate L-amino acids
      into such molecules, stereochemical interactions make such alpha-helices,
      invariably right-handed. Pseudomonas tolaasii Paine is the causal organism of the
      economically significant brown blotch disease of the cultivated mushroom Agaricus
      bisporus (Lange) Imbach. P. Tolaasii proceduces an extracellular lipodepsipeptide
      toxin, tolaasin, which causes the brown pitted lesions on the mushroom cap.
      Circular dichroism studies on tolaasin in a membrane-like environment indicate
      the presence of a left-handed alpha-helix, probably formed by a sequence of 7 D
      amino acids in the peptide. P. tolaasii represents the first reported example of
      an organism which has evolved the ability to biosynthesize a left-handed alpha
      helix.

PMID- 1991519
TI  - Nature of primary product(s) of D-glucose 6-phosphate dehydrogenase reaction. 13C
      and 31P NMR study.
AB  - Glucose 6-phosphate dehydrogenase catalyzes the oxidation of glucose 6-phosphate,
      resulting in the formation of 6-phosphogluconolactone. As this compound is
      unstable, it has not been characterized directly. NMR provides a way to directly
      monitor all components of a reaction and study their structure. Here we report
      some results on the glucose 6-phosphate dehydrogenase reaction using 31P and 13C
      NMR. Our results indicate that two different lactones, namely gamma (1-4) and
      delta (1-5) 6-phosphogluconolactones, are formed as products in this reaction.
      This is in contrast to an earlier suggestion that glucose 6-phosphate
      dehydrogenase produces only the delta-lactone. On the basis of these results, a
      new mechanisms for dehydrogenation of the sugar phosphate is proposed.

PMID- 1991520
TI  - Evidence for co-regulation of Cu,Zn superoxide dismutase and metallothionein gene
      expression in yeast through transcriptional control by copper via the ACE 1
      factor.
AB  - Saccharomyces cerevisiae mutant strain DTY26, lacking ACE1, the protein mediator
      for the induction of metallothionein gene expression, is unable to increase Cu,Zn
      superoxide dismutase mRNA in response to copper. In the wild-type strain DTY22
      transcription of both Cu,Zn superoxide dismutase and metallothionein genes is
      induced by copper and silver, as expected on the basis of previous results
      indicating that ACE1 binds only Ag(I) besides Cu(I). We conclude that at the
      transcriptional level Cu,ZnSOD is co-regulated with metallothionein. Furthermore,
      structural similarities between the two promoters were found, which could explain
      the co-regulation effect and the quantitative differences in the response of the
      two genes to copper.

PMID- 1991521
TI  - Swimming training increases the G4 acetylcholinesterase content of both fast
      ankle extensors and flexors.
AB  - The effect of endurance swimming training on AChE molecular forms was examined in
      2 groups of functionally antagonist rat muscles, including ankle extensors and
      flexors. This exercise regimen, which entails predominant dynamic activity (i.e.,
      involving extensive shortening) of both groups of muscles, resulted in marked
      selective G4 increases in all fast muscles. The G4 elevation exhibited by the
      ankle flexors was in sharp contrast to the G4 reduction reported in these same
      muscles following running training, during which their action is predominantly
      tonic. The results strengthen the conclusion that predominantly dynamic activity
      increases the G4 content of mature innervated fast muscles.

PMID- 1991522
TI  - The bulk of Ca2+ released to the myoplasm is free in the sarcoplasmic reticulum
      and does not unbind from calsequestrin.
AB  - Calsequestrin (CS) is the major Ca2+ binding protein contained in the lumen of
      sarcoplasmic reticulum (SR). Ca2+ binding properties and tissue concentration of
      CS of frog skeletal muscle were measured. At equilibrium, maximal Ca2+ binding
      capacity of purified CS was about 1.2 mumol Ca2+/mg protein. Apparent Kds for
      Ca2+ were around 50 microM in the absence of salts, around 0.9 mM in the presence
      of 100 mM KCl, and around 1.1 mM under 'physiological' conditions. Quantitation
      of CS in homogenates was accomplished by three methods (Stains-all staining,
      immunoblotting and 45Ca ligand overlay). Frog muscle contained about 0.5 mg of
      CS/g wet weight, that is 6.1 mM CS inside the SR. At rest the in situ free [Ca2+]
      of SR was calculated to be 3.6 mM, and, thus, CS is largely saturated with Ca2+.
      Moreover, computer simulations of Ca2+ release indicated that about 75% of Ca2+
      released during a twitch is free in the SR and does not unbind from CS.

PMID- 1991523
TI  - Interaction of cytochrome P-450scc with cytochrome b5.
AB  - Spectrophotometric, affinity chromatography and cross-linking experiments
      provided evidence that cytochrome P-450scc from bovine adrenocortical
      mitochondria forms a tight complex with cytochrome b5 from rabbit liver
      microsomes. In the reconstituted system cholesterol side chain activity of
      cytochrome P-450scc was enhanced by the addition of cytochrome b5.

PMID- 1991525
TI  - Life table analysis of fecundity in intravenously gonadotropin-releasing hormone
      treated patients with normogonadotropic and hypogonadotropic amenorrhea.
AB  - The success of pulsatile intravenous (IV) gonadotropin-releasing hormone (GnRH)
      treatment in patients with normogonadotropic and hypogonadotropic amenorrhea was
      studied retrospectively using life table analysis. Two hundred forty-four
      ovulatory cycles in 48 normogonadotropic and hypogonadotropic patients were
      evaluated. The cumulative conception rate after 12 cycles was 93%, with a mean
      conception rate of 22.5% per cycle. Comparing cycles 1 to 6 with cycles 7 to 12,
      no significant difference in conception rate was observed. Subdivisions were made
      relative to the presence of additional infertility factors, history of weight
      loss, actual weight, estrogenic status, and primary versus secondary amenorrhea.
      The life table curves of patients either with or without other infertility
      factors were significantly different. No statistically significant differences
      were found in the other subdivisions. It is concluded that IV GnRH therapy is
      highly successful in patients with normogonadotropic and hypogonadotropic
      amenorrhea, especially if no other infertility factors are present.

PMID- 1991524
TI  - Antibiotics: potential hazards to male fertility.
AB  - Individual agents within each of the major classes of antibiotics have been shown
      to have significant adverse effects on spermatogenesis or spermatozoal function
      in mammals. For humans, infertility or significant alterations in semen
      parameters have been well documented for the nitrofurans and for patients on
      sulfasalazine. Other commonly used antibiotics, such as minocycline, have been
      shown to be toxic to sperm at any concentration. Until further information is
      available, clinicians must keep in mind that treatment with antibiotics may
      adversely affect the fertility potential of men. It is possible that some classes
      of antibiotic agents, such as the penicillins or the quinolones, may have minimal
      effects on male fertility and maintain the clinical efficacy for patients
      requiring long-term antibiotic suppressive therapy. Further investigation is
      needed into the relative toxicity of antibiotics and the mechanisms by which
      antibiotics affect spermatogenesis and spermatozoal function. A background of the
      current state of knowledge regarding the adverse effects of antibiotics on male
      fertility is presented in this review.

PMID- 1991526
TI  - Polycystic ovary syndrome and bulimia.
AB  - One hundred fifty-three patients classified as suffering from polycystic ovarian
      syndrome (PCOS) and 109 patients who were suffering from a clear organic disorder
      or endocrinopathy received the bulimia investigation test (Edinburgh) (BITE)
      questionnaire for abnormal eating behaviors. Patients with PCOS showed a
      significant increase in their mean BITE score for approximately a third had
      abnormal eating patterns, and 6% have scores suggestive of clinical bulimia
      compared with only 1% of women in the group with organic endocrinopathies. The
      work suggests that women with PCOS should be screened for abnormal eating
      behaviors and raises the possibility that treatment by psychological means should
      be considered when abnormal eating behaviors are present.

PMID- 1991527
TI  - Evaluation and therapy of breakthrough bleeding in women using a triphasic oral
      contraceptive.
AB  - This study was designed to investigate the incidence and pattern of breakthrough
      bleeding (BTB) in 1,259 women who were prescribed for the first time a triphasic
      oral contraceptive (OC, 7-7-7) and to evaluate a hypothesis of management for BTB
      persisting after three cycles. The new users were compared with a control group
      of 696 women who had used various OCs for at least 6 months. The incidence of BTB
      in the control group was 16.8% and in the new users was 24.9%, 17.5%, and 15.3%
      in the first 3 months, respectively. Breakthrough bleeding occurred late in the 7
      7-7 package in 58% and early or midway through the package in 17% and 25%,
      respectively. We hypothesized that late-package BTB would improve if the patient
      was switched to a monophasic pill similar to the relatively estrogenic
      formulation of the beginning of the package and vice versa for early or
      midpackage BTB. Seventy women with BTB at 3 months were randomly given 0.5/35 or
      1/35 for a further 3 months. Breakthrough bleeding was more likely (P less than
      0.05) to improve in women switched to 1/35 compared with 0.5/35 regardless of
      where in the package BTB occurred.

PMID- 1991528
TI  - Endometrial epithelial cells in peritoneal fluid during the early follicular
      phase.
AB  - Peritoneal fluid (PF) was obtained during the early follicular phase in 24 women
      at laparoscopy as part of infertility investigation. The cells present in PF were
      pelleted and cultured. Developing endometrial epithelial cell colonies were
      identified in 19 women (79%). Identification of these cell colonies was
      facilitated using the monoclonal antibody BW 495/36 as specific marker. The
      number of endometrial epithelial cell colonies showed a large variation (1 to 200
      or more PF sample). No significant distinction in incidence and number of cell
      colonies was found between women with minimal (n = 11) and without endometriosis
      (n = 12). A significant correlation with number of cell colonies was found in
      women with infertility and no mechanical and male infertility factors. These data
      indicate that retrograde transport of viable endometrial cells during
      menstruation occurs in most women with patent tubes. Implications of the results
      for the relation between retrograde menstruation, endometriosis, and infertility
      are discussed.

PMID- 1991529
TI  - The incidence of multiple pregnancy after in vitro fertilization and embryo
      transfer, gamete, or zygote intrafallopian transfer.
AB  - This retrospective study concerns the incidence of multiple pregnancy after the
      replacement of three conceptus using different techniques of assisted
      reproduction. During a 2-year period, 713 in vitro fertilization-embryo transfers
      (IVF-ETs) with three embryos, 190 gamete intrafallopian transfers (GIFT) with
      three oocytes, and 161 zygote intrafallopian transfers (ZIFT) with three zygotes
      were performed. Although we observed significant differences in implantation and
      pregnancy rates (PRs), the three techniques resulted in high multiple PR. At 20
      weeks, 16% of GIFT pregnancies, 27% of ZIFT pregnancies, and 32% of IVF-ET
      pregnancies were multiple. Therefore we recommend to limit the number of
      conceptus transferred to a maximum of three in all cases.

PMID- 1991530
TI  - Effect of baseline ovarian cysts on in vitro fertilization and gamete
      intrafallopian transfer cycles.
AB  - The presence of ovarian cysts may compromise the success of in vitro
      fertilization (IVF) and gamete intrafallopian transfer (GIFT). We prospectively
      studied 212 consecutive ovulation induction cycles in 120 patients for IVF and/or
      GIFT. A baseline cyst was defined as any intraovarian cystic structure greater
      than or equal to 12 mm noted on ultrasonography before superovulation. Cycle
      outcomes were compared between patients with cysts (n = 62) versus those with no
      cysts (n = 150). There were no differences in follicular or luteal phase lengths
      or amount of human menopausal gonadotropins used. Peak estradiol (E2) levels were
      significantly lower and cancellation rates significantly higher in the cyst
      group. For noncanceled cycles, there were no significant differences in peak E2
      levels, the mean number of follicles greater than or equal to 12 mm, mature
      oocytes retrieved, or ova transferred for GIFT or embryos for IVF. The pregnancy
      rates overall and for noncanceled cycles were not significantly different.

PMID- 1991532
TI  - Delayed fertilization and poor embryonic development associated with impaired
      semen quality.
AB  - Delayed fertilization is common in cycles with immature oocytes. This phenomenon
      was observed in 42 of 423 with mature oocytes. Of the 42 cycles, 16 were excluded
      because of the presence of sperm autoantibodies. Sperm parameters of the
      remaining 26 (6.1%) cycles (group A) were compared with those in cycles with no
      fertilization at all (group B) and those in the control group (group C). The
      percentage of normal forms was 15% in group B and 24% in group A compared with
      51% in group C. Fertilization rates were 32% in group A compared with 81% in
      group C. The incidence of poor embryonic morphology was 82% in group A compared
      with 29% in group C. Delayed fertilization and poor embryonic morphology
      associated with impaired sperm quality is of clinical and prognostic importance.

PMID- 1991531
TI  - Intraperitoneal insemination in the treatment of male and unexplained
      infertility.
AB  - For couples with unexplained or male infertility, intraperitoneal (IP)
      insemination in induced cycles is a method that increases the chance of
      fertilization. Seventy-seven couples with male subfertility were subjected to 120
      IP insemination cycles and 31 with unexplained sterility to 44 cycles. As a
      consequence of the treatment, 23 pregnancies were obtained, with pregnancy rates
      of 23% per cycle and 32% per patient for unexplained infertility and 11% and 17%
      for male subfertility. Pregnancy loss rate was quite elevated: 9 clinical
      abortions and 1 ectopic. Intraperitoneal insemination appears to be a relatively
      noninvasive way to deal with unexplained or male factor infertility, well worth
      trying before moving on to more invasive and costly approaches, such as gamete
      intrafallopian transfer or in vitro fertilization.

PMID- 1991533
TI  - Comparison of the hamster sperm motility assay to the mouse one-cell and two-cell
      embryo bioassays as quality control tests for in vitro fertilization.
AB  - The hamster sperm motility assay, mouse one-cell embryo, and mouse two-cell
      embryo bioassays were used to test modified Tyrode's solution and modified Ham's
      F-10 (Gibco, Grand Island, NY) medium prepared in tap water versus ultrapure
      water. Factors influencing the ability of each assay to discriminate water
      quality were evaluated to characterize these assays for quality control use in
      the in vitro fertilization laboratory. The hamster sperm motility assay
      reproducibly detected differences in treatment without significant interanimal,
      interanalyst, or interassay variation. Interanalyst and interanimal variation
      significantly affected the ability to detect treatment differences using the
      mouse bioassays. Sample sizes needed to predict clinically significant treatment
      effects were calculated using varying assay conditions. Ham's F-10 medium can be
      tested with the hamster sperm motility assay.

PMID- 1991534
TI  - Discrimination between nonhyperactivated and classical hyperactivated motility
      patterns in human spermatozoa using computerized analysis.
AB  - The objective identification of human hyperactivated (HA) motility has been
      controversial. The present study defines new criteria for automatic sorting of
      all HA patterns that are consistent with the classical descriptions. Sperm from
      fertile men were prepared in Ham's F-10 medium. Based on the author's previously
      published slow-motion method, 342 sperm were selected that represented the non
      HA, circling high-curvature, thrashing, star, and helical patterns. Automatic
      sorting for HA was achieved with the use of three criteria: linearity less than
      or equal to 65 and velocity greater than or equal to 100 microns/s and head
      displacement greater than or equal to 7.5 microns. Additional criteria were
      determined for identifying each HA class separately. Whether using the new or old
      method, the incidence of HA is significantly associated with multiple
      fertilization endpoints.

PMID- 1991535
TI  - The presence of platelet-activating factor-like activity in human spermatozoa.
AB  - Evidence is provided for the existence of platelet-activating factor (PAF)-like
      activity in the lipid extracts of human spermatozoa. The PAF content of human
      spermatozoa based on [3H]-serotonin release from washed rabbit platelets was
      noted to be 1.45 pmol/10(8) sperm cells in highly purified motile spermatozoa. No
      PAF activity was associated with the seminal fluid. Platelet-activating factor
      content of spermatozoa may be related to its fertility potential.

PMID- 1991536
TI  - Synergistic effects of INTERCEED(TC7) and heparin in reducing adhesion formation
      in the rabbit uterine horn model.
AB  - Surgical adjuvants are commonly employed to reduce the frequency of postoperative
      adhesion development after reproductive pelvic surgery. The ability of
      indomethacin, promethazine dexamethasone, Intralipid, progesterone, and heparin
      to reduce adhesion formation in combination with INTERCEED(TC7) (Johnson and
      Johnson Medical, Inc., New Brunswick, NJ), an absorbable barrier that alone
      reduces adhesion formation, was examined in a rabbit uterine horn model. A
      significant reduction in adhesion formation was only observed with the
      combination of INTERCEED(TC7) plus heparin. In addition studies, heparin delivery
      by intraperitoneal (IP) lavage, intravenous injection, or intra-abdominal
      instillation failed to demonstrate efficacy. Similarly, heparin delivery with
      other barriers or IP instillates (carboxymethylcellulose or 32% Dextran 70)
      failed to reduce adhesion formation. We conclude that INTERCEED(TC7) can be
      efficaciously utilized as a carrier to deliver heparin to traumatized surfaces,
      thereby reducing adhesion formation.

PMID- 1991537
TI  - The effect of estradiol on the production and secretion of complement component 3
      by the rat uterus and surgically induced endometriotic tissue.
AB  - We have recently demonstrated that glandular epithelial cells isolated from human
      endometriotic tissue synthesize and secrete complement component 3 (C3).
      Furthermore, because C3 is capable of producing many of the immunological
      activities known to be associated with human endometriosis, we studied the
      production, secretion, and regulation of C3 using the rat model for
      endometriosis. Endometriosis was surgically induced in 20 adult female rats. The
      animals were then ovariectomized and one half were treated with estradiol (E2)
      for 3 days. Uterine luminal epithelial cells synthesized and secreted C3 only
      after E2 administration, whereas the uteri from control animals did not produce
      C3. In contrast, the ectopic endometrium from control animals produced and
      secreted C3, and this expression was strongly upregulated by in vivo E2
      administration. We conclude that surgically induced endometriosis in the rat has
      properties biochemically independent from the intact uterus and may serve as a
      useful model to further investigate the regulation of C3 synthesis from human
      endometriosis.

PMID- 1991538
TI  - Detection of a progesterone-induced secretory protein synthesized by the uteri
      but not the endometriotic implants of rats with induced endometriosis.
AB  - Steroids modulate the secretory activity of the uterus, but little is known of
      their effect on ectopic endometrium protein synthesis and secretion. We utilized
      two-dimensional electrophoresis to visualize proteins produced by the uteri and
      endometriotic implants of both steroid-treated and reproductively cyclic rats
      with and without surgically induced endometriosis. Of the greater than 300
      proteins visualized, only the uterine cultures from progesterone (P)-stimulated,
      estrogen-suppressed rats contained a distinctive glycoprotein (P-induced uterine
      protein-1; molecular weight [Mr] 70,000; isoelectric point [pI] 5.7). This
      protein was not detected in any of the endometriotic implant cultures.
      Progesterone-induced uterine protein-1 could play a role in luteal or endometrial
      physiology and may be valuable in assessing endometrial function. The aberrant
      secretory behavior of the ectopic endometrium suggests a possible involvement in
      the reproductive dysfunction associated with endometriosis.

PMID- 1991539
TI  - Time-related effects of gonadotropin-releasing hormone analog treatment in
      experimentally induced endometriosis in the rat.
AB  - The purpose of our study was to characterize the time-dependent effect of
      gonadotropin-releasing hormone analog (GnRH-a) therapy on endometriosis explant
      using the rat model. Endometriosis was induced in 60 mature female rats. One
      group of treated animals as well as controls were killed at 2, 4, 6 and 8 weeks
      of treatment at which time the explant was evaluated. Explant volume was
      significantly reduced in all treatment groups, an effect that was more
      significant in animals treated for greater than or equal to 4 weeks compared with
      those treated for only 2 weeks. We conclude that GnRH-a treatment caused gradual
      regression of endometrial explant that was effectively complete by 4 weeks of
      treatment. We further conclude that this experimental model may be useful in the
      evaluation of other modes of endometriosis therapy.

PMID- 1991541
TI  - The effect of unilateral versus bilateral tubal cannulation and the number of
      oocytes transferred on the outcome of gamete intrafallopian transfer.
AB  - A comparison of results of GIFT procedures using unilateral and bilateral tubal
      cannulation was made. There was no difference in outcome between these two
      methods, with the unilateral approach having some advantages over the bilateral
      procedure. Pregnancy rates decreased as the number of oocytes transferred was
      reduced.

PMID- 1991540
TI  - A clinical pregnancy after a simple method of zona cutting, cryopreservation, and
      zygote intrafallopian transfer.
AB  - A 30-year-old nulliparous woman, who was infertile for greater than 3 years,
      conceived after the procedures of a simple method of zona cutting,
      cryopreservation, and ZIFT. This case illustrates: (1) acid medium, chymotrypsin,
      or sucrose are not needed for the procedure of zona cutting; (2) the zygotes
      resulting from zona cutting survive through freezing and thawing; and (3) oocyte
      retrieval can be done concomitant with conservative surgery for endometriosis.

PMID- 1991542
TI  - Embryo quality and pregnancy rates in patients attempting pregnancy through in
      vitro fertilization.
AB  - Patients at low risk for producing abnormal gametes produce a wide range of
      embryo qualities that correlate well with PRs. These data may be useful in
      counseling patients and in reviewing treatment and laboratory protocols.

PMID- 1991544
TI  - Are cardiolipin antibody levels elevated in endometriosis?

PMID- 1991543
TI  - Predictive value of the active renin assay for the diagnosis of ectopic
      pregnancy.
AB  - The increasing frequency of EP and the need for its early diagnosis have focused
      our interest on the research of biochemical markers. We have established hormonal
      values in the plasma of 99 spontaneous ongoing pregnancies between the 4th and
      10th weeks of amenorrhea, in 21 EPs, and 20 cases of early abortion. We have
      examined the predictive values of trophoblastic and CL production in pathological
      pregnancies. The association of low hCG and low active renin appears to be able
      to discriminate between ectopic and abortive spontaneous gestations.

PMID- 1991545
TI  - Inhibition of human sperm-zona pellucida and sperm-oolemma binding by antisperm
      antibodies.
AB  - The results of this preliminary investigation suggest that antisperm antibodies
      interfere predominantly with sperm-zona pellucida binding. The observation of
      similar numbers of control (Ab-) and test (Ab+) sperm bound to the oolemma
      implies that the antibody-mediated inhibition of capacitation, acrosome reaction,
      or oolemma binding may not be major causes of failed fertilization with sperm
      autoimmunity. However, only seven patients were studied, and further
      investigation with larger numbers of subjects are required.

PMID- 1991547
TI  - Who inherits the embryo?

PMID- 1991546
TI  - In vitro fertilization techniques with frozen-thawed sperm: a method for
      preserving the progenitive potential of Hodgkin patients.
AB  - The banked sperm of 5 of 13 Hodgkin patients was thawed for assisted
      reproduction. The post-thaw sperm characteristics were extremely impaired.
      Nevertheless, in 80% of all trials fertilization in vitro was obtained and
      conceptus could be transferred. All spouses became pregnant and seven healthy
      infants were born. One could recommend every Hodgkin patient to bank his sperm
      before chemotherapy. In vitro fertilization techniques with this frozen-thawed
      sperm reveal promising results in comparison with artificial insemination to
      maintain the reproductive capacity of male Hodgkin patients.

PMID- 1991548
TI  - Effects of mesodermal tissues on avian neural crest cell migration.
AB  - We have used microsurgical techniques to investigate the effects of embryonic
      mesodermal tissues on the pattern of chick neural crest cell migration in the
      trunk. Segmental plate or lateral plate mesenchyme was transplanted into regions
      encountered by neural crest cells. We found that neural crest cells are able to
      migrate through lateral plate mesenchyme but not through segmental plate tissue
      until this tissue differentiates into a sclerotome. After this stage, segmental
      migration is controlled by the subdivision of the sclerotome into a rostral and a
      caudal half; when the rostrocaudal orientation of the sclerotomes is reversed by
      rotating the segmental plate 180 degrees about its rostrocaudal axis, neural
      crest cells migrate through the portion of the sclerotome that was originally
      rostral.

PMID- 1991549
TI  - Isolation of cDNAs partially encoding four Xenopus Wnt-1/int-1-related proteins
      and characterization of their transient expression during embryonic development.
AB  - To begin to study the functions of the Wnt-1/int-1 gene family during vertebrate
      development, we have isolated four Xenopus laevis cDNAs encoding the partial
      sequence of proteins homologous to Wnt-1/int-1. Xwnt-3, Xwnt-4, Xwnt-5A, and Xwnt
      8 demonstrate between 35 and 50% amino acid identity with X. laevis Wnt-1/int-1
      and most cysteine residues are conserved. Xwnt-4 and Xwnt-3 transcripts are
      detected only during the neurula through tadpole stages of development.
      Expression of Xwnt-8 is observable during gastrulation, declines during
      neurulation, and is undetectable by the tadpole stage of development. Xwnt-5A
      transcripts are most prevalent in RNA from oocytes and tadpoles, although low
      level expression is detected at all stages examined. The temporal changes in
      expression of these transcripts imply a unique role for each Xwnt during
      embryogenesis.

PMID- 1991550
TI  - Cell-cell interactions trigger the rapid induction of a specific high mobility
      group-like protein during early stages of conjugation in Tetrahymena.
AB  - Conjugation in Tetrahymena represents an ordered developmental pathway which
      represents the sexual phase of the ciliate life cycle. This pathway is initiated
      when starved cells of opposite mating types are mixed and are allowed to make a
      series of cell-cell contacts (a period termed costimulation) which lead to the
      formation of mating pairs. Here, we demonstrate that two previously described
      abundant high mobility group (HMG)-like proteins, HMG B and HMG C, whose
      synthesis appeared to be coordinately regulated in vegetative cells, are not
      required during the same stages of conjugation. The level of mRNA for both HMG B
      and HMG C is high during vegetative growth and during the development of new
      macronuclei. However, specific induction of HMG B mRNA is observed soon after
      cells of opposite mating types are mixed. Thus, the genes which encode HMG B and
      HMG C in Tetrahymena can be controlled independently or coordinately. Nuclear run
      on experiments show that a significant factor underlying the rapid induction of
      HMG B message early in the sexual cycle is an increase in the transcriptional
      activity of the HMG B gene. Experiments are presented which show that this
      induction of HMG B message requires protein synthesis and is dependent upon the
      cell-cell contacts made during costimulation. Essentially all of the HMG B
      protein, which is newly synthesized during this period, is targeted to parental
      macronuclei where it serves an as yet undetermined function(s).

PMID- 1991551
TI  - The sequence of the Arbacia punctulata bindin cDNA and implications for the
      structural basis of species-specific sperm adhesion and fertilization.
AB  - Bindin is the major protein component of the acrosome granule of sea urchin sperm
      which mediates the species-specific adhesion of sperm to the egg surface during
      fertilization. Bindin isolated from both Arbacia punctulata and
      Strongylocentrotus purpuratus sperm demonstrate a distinct adhesive preference
      for eggs of the same species although a significant amount of cross-species
      reactivity is observed. Here we describe the isolation and sequence of A.
      punctulata bindin cDNA clones and a comparison of the predicted protein sequence
      with the sequence previously reported for S. purpuratus bindin (Gao et al., 1986,
      Proc. Natl. Acad. Sci., USA 83, 8634-8638). Bindins from these genera show
      substantial sequence similarity in both the mature bindin domain and the
      probindin precursor region. The most striking identity is a region of 42
      conserved amino acids in the central part of the mature bindins. This conserved
      domain may be responsible for conserved functions of bindin. Regions flanking
      this conserved element on both the amino and carboxyl side are more highly
      divergent, suggesting that they are responsible for the species-specific
      properties of bindin. The mature A. punctulata sequence contains a putative
      transmembrane segment between residues 431 and 451 that is absent from S.
      purpuratus bindin. This structural element may account for the previous
      observation that isolated A. punctulata bindin uniquely forms multilamellar
      structures reminiscent of lipid bilayers and binds significant amounts of
      phospholipid and detergent. The structure of this hydrophobic segment also
      displays a number of similarities to viral fusion peptides.

PMID- 1991552
TI  - Initiation of DNA replication cycle in fertilized eggs of the starfish, Asterina
      pectinifera.
AB  - Starfish oocytes or eggs were inseminated at various times between first
      prometaphase and pronuclear stage, and were subsequently labeled with the
      thymidine analogue 5-bromo-2'-deoxyuridine (BrdU) in order to detect the onset of
      DNA synthesis phase (S phase) during the first cell cycle using a monoclonal
      antibody against BrdU. The interval between fertilization and the first S phase
      was found to be constant (30-45 min, depending on batches) in eggs fertilized
      after formation of the first polar body. Eggs fertilized before first polar body
      formation, however, always entered the S phase 10-20 min after the second polar
      body formation. On the basis of these observations we conclude that (i) the chain
      of events triggered by fertilization, collectively called "postactivation
      process" for the first S phase, goes on in parallel with the process of
      maturation and (ii) only the final step of the postactivation process is arrested
      until the termination of meiosis. In eggs that had been fertilized before the
      first polar body formation, the female and male pronuclei exhibited uniformly
      distributed chromatin soon after the second polar body formation. In eggs that
      had been fertilized after the second polar body formation, however, the chromatin
      of the pronuclei remained fibrillar even during the S phase. Thus full
      decondensation of chromatin appears to depend on a certain advance in the
      postactivation process.

PMID- 1991553
TI  - Transforming growth factor beta type 1 binds to collagen IV of basement membrane
      matrix: implications for development.
AB  - The interaction of transforming growth factor beta (TGF beta) with extracellular
      matrix macromolecules was examined by using radiolabeled TGF beta and various
      matrix macromolecules immobilized on nitrocellulose. TGF beta bound to collagen
      IV with greater affinity than to other extracellular matrix macromolecules
      tested. Neither laminin nor fibronectin, both of which bind type IV collagen,
      interfered with the binding of TGF beta to type IV collagen. TGF beta 2 competed
      effectively with TGF beta 1 for binding to type IV collagen. The biological
      effect of TGF beta was tested by an assay based on inhibition of proliferation of
      an osteoblast cell line, MC3T3-E1. The results demonstrated that the effect of
      TGF beta 1 was sustained when cells were grown on type IV collagen compared to
      cells grown on laminin, collagen type I, and plastic. These results demonstrate
      that extracellular matrix components may function as an affinity matrix for
      binding and immobilizing soluble growth and differentiation factors. In view of
      the demonstrated role of basement membranes in development the present results
      imply an important function for transforming growth factor beta bound to collagen
      IV in local regulation of cell proliferation and differentiation.

PMID- 1991554
TI  - Pigment patterns in neural crest chimeras constructed from quail and guinea fowl
      embryos.
AB  - The pattern of pigmentation in bird embryos is determined by the spatial
      organization of melanocyte differentiation. Some of the results from recent,
      neural crest transplantation experiments support a model based on a prepattern in
      the feathers; others could be interpreted in terms of a nonspecific pattern
      resulting from a failure of the crest cells to read the positional values in
      another species. To distinguish between these possibilities, the crucial test is
      to construct chimeras from two species with different pigment patterns. We have
      examined the wing plumage of quail and guinea fowl embryos. The quail has a
      characteristic pattern of pigmented and unpigmented feather papillae, whereas the
      guinea fowl shows uniform pigmentation. Chimeras were constructed by grafting
      wing buds isotopically between embryos. The wing buds were transplanted before
      they had become invaded by neural crest cells. Quail wing buds grafted to the
      guinea fowl developed, in most cases, a pigment pattern resembling that of the
      quail and not that of the guinea fowl. A few cases became uniformly pigmented and
      appeared to represent nonspecific patterns. The reciprocal grafts (guinea fowl
      wing buds grafted to the quail) became pigmented all over. We found evidence that
      the timing of melanocyte differentiation is controlled by cues in the feather
      papillae. Some cases developed a severe inflammatory response. The model which
      best accounts for these findings--and which can account for inconsistencies in
      previous reports--is the following. A prepattern is present in the feathers and
      this can control the differentiation of melanoblasts, even if they come from a
      different species. The local cues which constitute the prepattern are not
      positional values. In some chimeras melanoblasts fail to respond to the
      prepattern and so a nonspecific pattern of uniform pigmentation is produced.

PMID- 1991555
TI  - Skeletal muscle satellite cell diversity: satellite cells form fibers of
      different types in cell culture.
AB  - Following skeletal muscle injury, new fibers form from resident satellite cells
      which reestablish the fiber composition of the original muscle. We have used a
      cell culture system to analyze satellite cells isolated from adult chicken and
      quail pectoralis major (PM; a fast muscle) and anterior latissimus dorsi (ALD; a
      slow muscle) to determine if satellite cells isolated from fast or slow muscles
      produce one or several types of fibers when they form new fibers in vitro in the
      absence of innervation or a specific extracellular milieu. The types of fibers
      formed in satellite cell cultures were determined using immunoblotting and
      immunocytochemistry with monoclonal antibodies specific for avian fast and slow
      myosin heavy chain (MHC) isoforms. We found that satellite cells were of
      different types and that fast and slow muscles differed in the percentage of each
      type they contained. Primary satellite cells isolated from the PM formed only
      fast fibers, while up to 25% of those isolated from ALD formed fibers that were
      both fast and slow (fast/slow fibers), the remainder being fast only. Fast/slow
      fibers formed from chicken satellite cells expressed slow MHC1, while slow MHC2
      predominated in fast/slow fibers formed from quail satellite cells. Prolonged
      primary culture did not alter the relative proportions of fast to fast/slow
      fibers in high density cultures of either chicken or quail satellite cells. No
      change in commitment was observed in fibers formed from chicken satellite cell
      progeny repeatedly subcultured at high density, while fibers formed from
      subcultured quail satellite cell progeny demonstrated increasing commitment to
      fast/slow fiber type formation. Quail satellite cells cloned from high density
      cultures formed colonies that demonstrated a similar change in commitment from
      fast to fast/slow, as did serially subcloned individual satellite cell progeny,
      indicating that the observed change from fast to fast/slow differentiation
      resulted from intrinsic changes within a satellite cell. Thus satellite cells
      freshly isolated from adult chicken and quail are committed to form fibers of at
      least two types, satellite cells of these two types are found in different
      proportions in fast and slow muscles, and repeated cell proliferation of quail
      satellite cell progeny may alter satellite cell progeny to increasingly form
      fibers of a single type.

PMID- 1991556
TI  - Changing interactions between astrocytes and neurons during CNS maturation.
AB  - The environments of the developing brain and injured adult brain differ in their
      abilities to support axonal growth. To determine if astrocytes contribute to this
      difference, neurons were plated onto astrocytes cultured from the neonatal rat
      cortex and from the injured adult brain. Two patterns of neurite growth were
      observed in these two astrocyte culture systems. Neurons contacting the neonatal
      astrocytes had neurites that were twice as long as those contacting the injured
      adult astrocytes. Furthermore, in cultures with neonatal astrocytes, neurites
      faithfully followed the astrocytic processes, maximizing their contact, while in
      cultures of injured adult astrocytes, the neurites had a tendency to cross the
      processes orthogonally, minimizing their interaction with the astrocytes. When
      neurons were grown suspended over either neonatal or injured adult astrocytes, no
      difference in neurite length or the pattern of neurite growth was observed,
      indicating that neurite growth was not differentially affected by soluble factors
      released from the two populations of astrocytes. The addition of fetal calf
      serum, which is known to contain protease inhibitors, did not alter neurite
      growth when compared to serum-free medium, suggesting that a substantial
      difference in protease activity does not account for the variations in neurite
      length observed. Based on these results, it appears that the molecular components
      of the external surface of injured adult astrocytes do not support neurite growth
      to the same extent as those found on neonatal astrocytes. The differing abilities
      of these two populations of cultured astrocytes to support neurite growth in
      culture may reflect a change in the functional role of these cells that occurs
      during the development of the central nervous system.

PMID- 1991557
TI  - Organization, nucleation, and acetylation of microtubules in Xenopus laevis
      oocytes: a study by confocal immunofluorescence microscopy.
AB  - Anti-tubulin immunofluorescence and laser-scanning confocal microscopy were used
      to examine microtubule organization during Xenopus oogenesis (Dumont stages I
      VI). Stage I oocytes contained a poorly ordered microtubule array, characterized
      by concentrations of microtubule in the cortex, surrounding the germinal vesicle,
      and associated with the mitochondrial mass. No focus of microtubule organization
      was detectable by optical sectioning or in microtubule regrowth experiments,
      suggesting that stage I oocytes lack a functional MTOC. The microtubule array
      becomes progressively more complex and polarized during oogenesis; an extensive
      array of microtubules and microtubule bundles was apparent in the animal
      hemisphere of stage VI oocytes, and a less ordered array was observed in the
      vegetal hemisphere. A dense network of microtubules surrounded the germinal
      vesicle, apparently extending from a tubulin- and microtubule-rich region of
      cytoplasm adjacent to the vegetal surface of the GV. The organization of
      microtubules in normal oocytes, in oocytes recovering from cold-induced
      microtubule depolymerization, and in enucleated oocytes, suggested that the
      germinal vesicle serves as an MTOC in stage VI oocytes. Antibodies to acetylated
      alpha-tubulin revealed numerous acetylated, presumably stable, microtubules in
      stage I and stage VI oocytes. The array of oocyte microtubules thus might
      function as a stable framework for the localization of developmentally important
      molecules and organelles during oogenesis.

PMID- 1991558
TI  - Tcp-1 gene is not responsible for the maternal lethality effect of Thp mutation
      in mice.
AB  - Embryos receiving either the Thp or the twLub2 mutation from their mother die
      during gestation. In contrast, heterozygous embryos receiving the mutant
      chromosome from the father are completely viable. In both Thp and twLub2 mutants,
      one chromosome 17 carries a deletion, which suggests the existence of a discrete
      maternal lethality effect locus (Tme). In the region whose deletion is
      responsible for the Thp or twLub2 mutation, a single gene has been cloned so far,
      the Tcp-1 gene. In the present study, we examined the expression of Tcp-1 gene in
      mutant embryos carrying either a maternal or a paternal Thp chromosome to test
      whether this gene could be involved in the Tme effect. We found that the levels
      of Tcp-1-specific transcripts were similar in both mutant embryos from reciprocal
      crosses and corresponded to half the levels found in the normal littermates. In
      addition, the paternal and maternal Tcp-1 alleles had identical methylation
      patterns. These results indicate that Tcp-1 is not responsible for the maternal
      lethality effect, and therefore is not located at the Tme locus.

PMID- 1991559
TI  - Cell lineages in Hydra: isolation and characterization of an interstitial stem
      cell restricted to egg production in Hydra oligactis.
AB  - In an attempt to isolate unipotent stem cells (progenitors to the nerve cells,
      nematocytes, gland cells, and gametes) from Hydra oligactis females, animals were
      treated with a drug (hydroxyurea, HU) that preferentially lowers or eliminates
      the interstitial stem cells, leaving the epithelial tissue intact. In this
      epithelial environment, interstitial cells remaining after treatment will
      proliferate and differentiate, permitting a long-term analysis of their
      developmental capabilities. Following treatment of females with HU, animals were
      isolated that contained interstitial cells that gave rise to eggs only. Two
      clones of animals containing these cells were propagated for several years and
      the growth and differentiation behavior of the interstitial cells examined in
      their asexually produced offspring. During this time, the cells displayed an
      extensive proliferative capacity (classifying them as stem cells) and remained
      restricted to egg differentiation. It is proposed that both the sperm- and the
      egg-restricted stem cells arise from a multipotent stem cell, which also gives
      rise to the somatic cells (see above), and that, in hydra, sex is ultimately
      determined by interactions between cells of the two germ cell lineages.

PMID- 1991560
TI  - Primary mesenchyme cell migration requires a chondroitin sulfate/dermatan sulfate
      proteoglycan.
AB  - Primary mesenchyme cell migration in the sea urchin embryo is inhibited by
      sulfate deprivation and exposure to exogenous beta-D-xylosides, two treatments
      known to disrupt proteoglycan synthesis. We show that in the developing sea
      urchin, exogenous xyloside affects the synthesis by the primary mesenchyme cells
      of a very large, cell surface chondroitin sulfate/dermatan sulfate proteoglycan.
      This proteoglycan is present in a partially purified fraction that restores
      migratory ability to defective cells in vitro. The integrity of this chondroitin
      sulfate/dermatan sulfate proteoglycan appears essential for primary mesenchyme
      cell migration since treatment of actively migrating cells with chondroitinase
      ABC reversibly inhibited their migration in vitro.

PMID- 1991561
TI  - Isolation, characterization, and localization of a sperm-bound N
      acetylglucosaminidase that is indispensable for fertilization in the ascidian,
      Phallusia mammillata.
AB  - N-Acetylglucosaminidase (GlcNAc'ase), which possesses by far the highest activity
      of all Phallusia mammillata sperm glycosidases, was isolated and purified using
      DEAE-cellulose, phenyl-Sepharose, and concanavalin A affinity chromatography. The
      molecular size of the native enzyme estimated by G-200 gel permeation was 158
      kDa. On SDS-PAGE, the denatured enzyme migrated as a single band with a Mr of 78
      kDa. This indicates that under nondenaturing conditions the GlcNAc'ase prevails
      as a dimer. The molecular activity of the enzyme was determined to be 3.7 x 10(5)
      U/mumole, the Km for p-NP-GlcNAc was 0.65 mM, and the Ki for GlcNAc was 5.5 mM.
      It has been suggested that gamete binding in ascidians might be mediated by an
      enzyme-substrate complex established between a sperm glycosidase and
      corresponding glycosides on the vitelline coat. Thus, the GlcNAc'ase should be
      present as an exoenzyme at the proper place on the sperm surface membrane, i.e.,
      on the sperm tip and possibly over the mitochondrial region. We localized the
      enzyme with fluorescence and electron microscopy using the neoglycoprotein BSA-p
      aminophenyl-N-acetyl-beta-D-glucosaminide (BSA-GlcNAc) or concanavalin A coupled
      either to fluorochromes or gold particles. Labeling of unreacted and activated
      sperm revealed three distinct binding sites, namely at the sperm tip, over the
      mitochondrion, and at the head-tail junction. In reacted sperm strong labeling
      was observed over the translocated mitochondrion as well as at the sperm tip. An
      intensive binding was observed along the rim which borders the cap-like structure
      at the sperm tip. The distribution of the enzyme reflected by these binding
      patterns accounts well for the suggested function. Using N-acetylglucosaminono
      1,5-lactone oxime, a novel, highly specific inhibitor of GlcNAc'ase, we were able
      to show that this enzyme is indispensable for fertilization of intact eggs, but
      not of eggs deprived of their vitelline coat. These observations are discussed in
      terms of functional relationships which may exist between this enzyme, sperm
      binding, gamete recognition, and penetration of the vitelline coat.

PMID- 1991562
TI  - A kinematic analysis of gynoecial growth in Lilium longiflorum: surface growth
      patterns in all floral organs are triphasic.
AB  - Sequential marking experiments combined with histological and morphological
      examination indicate that growth of the gynoecium in Lilium longiflorum Thunb.
      (Easter lily) is triphasic. Phase I (gynoecia less than 10 mm in length) is
      characterized by spatial and temporal variation in local relative growth rate and
      mitotic index throughout the entire gynoecium. In Phase II (10-100 mm), a steady
      growth peak is restricted to the proximal 5 to 15 mm of the style, while the
      ovary shows uniform growth. In Phase III (100-135 mm), the ovary ceases growth
      and the maximal growth zone of the gynoecium migrates from the proximal to the
      distal end of the style. Comparison of surface growth patterns and
      differentiation events in the gynoecium to those previously described in the
      tepal and another demonstrates the triphasic nature of growth in the whole lily
      flower.

PMID- 1991563
TI  - Integrins play an essential role in somite adhesion to the embryonic axis.
AB  - Integrins are proteins that mediate cell adhesion, mainly to the extracellular
      matrix. One of the first integrins discovered belongs to the beta 1 class of
      avian integrins and is defined by a monoclonal antibody, CSAT. Using a whole
      embryo culture system we injected nanoliter quantities of CSAT caudolateral to
      the last somite of early quail embryos. The CSAT antibodies, but not control
      antibodies, resulted in a striking lateral translocation of somites. Relatively
      higher doses or longer incubation times increased the severity of the effect. We
      conclude that somite segmentation per se is not influenced by CSAT, but that
      somite adhesion to axial structures requires integrin-mediated ECM adhesions.

PMID- 1991564
TI  - Distribution of myosin mRNA during development and regeneration of skeletal
      muscle fibers.
AB  - Myosin mRNA distribution among subcellular compartments of anterior tibialis
      muscles in rabbit is monitored by in situ hybridization. A high density of mRNA
      was widely distributed throughout myotubes from 29-day fetal muscle and from
      regenerating adult muscle. All cytoplasmic spaces contained mRNA except where
      scattered myofibrils and centrally located nuclei were found. In fibers from 22
      week-old rabbits, myosin mRNA was concentrated under the sarcolemma and excluded
      from the consolidated myofibrils and peripheral nuclei. The dispersal of mRNA
      through the cytoplasm in myotubes suggests that translation of myosin is
      widespread and that rapid myofibril assembly can occur throughout the fiber.

PMID- 1991565
TI  - A Brassica S locus gene promoter directs sporophytic expression in the anther
      tapetum of transgenic Arabidopsis.
AB  - The S locus glycoprotein (SLG) gene of Brassica encodes stigmatic glycoproteins
      that are implicated in the pollen-stigma interaction of self-incompatibility. We
      have transformed the related plant Arabidopsis thaliana with a chimaeric gene
      consisting of the promoter region of an SLG gene fused to the reporter gene beta
      glucuronidase (GUS). In transgenic plants the gene was expressed in two cell
      types of the flower. In stigmas, the timing and distribution of GUS activity was
      similar to that previously described for SLG expression in Brassica. In anthers,
      expression was detected at an earlier stage of flower development with GUS
      activity restricted to the tapetal cell layer. The novel finding of SLG-promoter
      activity in the anther supports the hypothesis that sporophytic control of self
      incompatibility is a result of SLG-gene expression in the tapetum.

PMID- 1991566
TI  - Inositol phospho-oligosaccharide stimulates cell proliferation in the early
      developing inner ear.
AB  - The ability of an inositol phospho-oligosaccharide (POS) to mimic the mitogenic
      effects of nerve growth factor (NGF) and insulin on the early development of the
      inner ear was investigated. POS (10 microM) stimulated the incorporation of
      [3H]thymidine into the cochleovestibular ganglion by 3.9-fold. NGF (50 ng/ml)
      stimulation was 4.7-fold. POS and NGF showed no additivity. Cells induced to
      proliferate by POS overlapped with those expressing NGF receptors. POS, like
      insulin, potentiated the mitogenic effect of bombesin on the otic vesicle
      epithelium. DNA synthesis in the presence of bombesin (100 nM) plus POS (10
      microM) was increased by 6.4-fold. POS stimulation was not additive with insulin.
      The results suggest that POS may play a role in growth factor regulation of cell
      proliferation during embryonic development.

PMID- 1991567
TI  - Archaeology of NIDDM. Excavation of the "thrifty" genotype.
AB  - Since the 1940s, numerous cases of non-insulin-dependent diabetes mellitus
      (NIDDM) have been observed in certain American Indian populations. Extremely high
      prevalence rates of NIDDM occur most strikingly in several tribes of Paleo
      Indians, whose ancestors migrated to North America greater than 11,000 yr ago.
      Archaeological evidence from that period indicates that certain groups of Paleo
      Indians maintained an arctic-like hunter-gatherer life-style in an area in
      temperate North America ranging from Wyoming to Arizona. This life-style featured
      a reliance on unpredictable big game species as a major food source. However, at
      this time, big game species were becoming extinct. It is hypothesized that those
      Paleo-Indians who relied on big game as a food source developed a "thrifty"
      genotype that allowed a selective advantage during the periods of fasting that
      occurred between big game kills. It also is hypothesized that this thrifty
      genotype in these Indians may contribute to NIDDM when a sedentary life-style is
      adopted and food sources are constant. Because insulin resistance in muscle is a
      major feature of NIDDM, it is possible that insulin resistance per se is the
      phenotypic expression of the thrifty genotype.

PMID- 1991568
TI  - Banting lecture 1990. Beta-cells in type II diabetes mellitus.
AB  - In 1960, immunoassays of insulin first demonstrated significant quantities of
      circulating hormone in non-insulin-dependent (type II) diabetes and for 30 yr
      have fostered debate as to whether a beta-cell abnormality plays an etiological
      role in this syndrome. Early efforts to determine the adequacy of islet beta-cell
      function showed that obesity and its associated insulin resistance were major
      confounding variables. Subsequently, it was recognized that glucose not only
      directly regulated insulin synthesis and secretion but moderated all other islet
      signals, including other substrates, hormones, and neural factors. When both
      obesity and glucose are taken into account, it becomes clear that patients with
      fasting hyperglycemia all have abnormal islet function. Type II diabetes is
      characterized by a defect in first-phase or acute glucose-induced insulin
      secretion and a deficiency in the ability of glucose to potentiate other islet
      nonglucose beta-cell secretagogues. The resulting hyperglycemia compensates for
      the defective glucose potentiation and maintains nearly normal basal insulin
      levels and insulin responses to nonglucose secretagogues but does not correct the
      defect in first-phase glucose-induced insulin release. Before the development of
      fasting hyperglycemia, only first-phase glucose-induced insulin secretion is
      obviously defective. This is because progressive islet failure is matched by
      rising glucose levels to maintain basal and second-phase insulin output. The
      relationship between islet function and fasting plasma glucose is steeply
      curvilinear, so that there is a 75% loss of beta-cell function by the time the
      diagnostic level of 140 mg/dl is exceeded. This new steady state is characterized
      by glucose overproduction and inefficient utilization. Insulin resistance is also
      present in most patients and contributes to the hyperglycemia by augmenting the
      glucose levels needed for compensation. Decompensation and absolute
      hypoinsulinemia occur when the renal threshold for glucose is exceeded and
      prevents further elevation of circulating glucose. The etiology of the islet beta
      cell lesion is not known, but a hypothesis based on basal hyperproinsulinemia and
      islet amyloid deposits in the pancreas of type II diabetes is reviewed. The
      recent discovery of the islet amyloid polypeptide (IAPP) or amylin, which is the
      major constituent of islet amyloid deposits, is integrated into this hypothesis.
      It is suggested that pro-IAPP and proinsulin processing and mature peptide
      secretion normally occur together and that abnormal processing, secondary to or
      in conjunction with defects in hormone secretion, lead to progressive
      accumulation of intracellular IAPP and pro-IAPP, which in cats, monkeys, and
      humans form intracellular fibrils and amyloid deposits with a loss of beta-cell
      mass.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1991569
TI  - Comparative modulations of insulin secretion, pancreatic insulin content, and
      proinsulin mRNA in rats. Effects of 50% pancreatectomy and dexamethasone
      administration.
AB  - These studies compared measurements of in vivo insulin secretion, insulin stores,
      and insulin synthesis. Rats were studied at 24 wk of age, either 1 or 20 wk after
      a sham operation (Sham) or 50% pancreatectomy (Px), reducing beta-cell number. By
      20 wk after surgery, an adaptation to pancreatectomy was apparent from results of
      serial glucose tolerance tests, done in a preliminary protocol. Some of the rats
      also received dexamethasone (ShamDex and PxDex, respectively), imposing insulin
      resistance. Insulin secretion was assessed with the acute insulin response to
      arginine under basal (AIRbas) and maximum glucose-potentiated (AIRmax) states.
      Pancreatic insulin was measured, and insulin synthesis was estimated by
      measurement of proinsulin mRNA. At 1 wk after surgery, there was no difference
      among Sham and Px rats in AIRbas, but in the Px rats, expected reductions of
      AIRmax, pancreatic insulin, and proinsulin mRNA were found. ShamDex rats had a
      markedly augmented AIRbas and increased AIRmax and proinsulin mRNA. However,
      pancreatic insulin was reduced both in ShamDex and PxDex rats. At 20 wk after
      surgery, the predicted adaptation to Px was substantiated by AIRmax and
      proinsulin mRNA in Px rats not different from those in Sham rats, but pancreatic
      insulin in the Px rats remained low. AIRbas and proinsulin mRNA were augmented in
      ShamDex and PxDex rats, but pancreatic insulin was again reduced, and in PxDex
      rats, low AIRmax and fed hyperglycemia were seen. Linear correlations of AIRbas
      and AIRmax with proinsulin mRNA were observed over a roughly fourfold range of
      secretion and synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1991570
TI  - O-linked oligosaccharides on insulin receptor.
AB  - The insulin receptor, an integral membrane glycoprotein, is synthesized as a
      single-chain precursor that is cleaved to produce two mature subunits, both of
      which contain N-linked oligosaccharide chains and covalently linked fatty acids.
      We report that the beta-subunit also contains O-linked oligosaccharides. The
      proreceptor, alpha-subunit, and beta-subunit were labeled with [3H]mannose and
      [3H]galactose in the presence or absence of an inhibitor of O-linked
      glycosylation. Tryptic peptides from each component were separated by reverse
      phase high-performance liquid chromatography. N- and O-linked oligosaccharide
      chains were identified on these peptides by specific enzymatic digestions. The
      proreceptor and alpha-subunit contained only N-linked oligosaccharides, whereas
      the beta-subunit contained both N- and O-linked oligosaccharides. The O-linked
      oligosaccharide chains were attached to a single tryptic fraction of the beta
      subunit, which also contained N-linked chains. This fraction was further
      localized to the NH2-terminal tryptic peptide of the beta-subunit by specific
      immunoprecipitation with an anti-peptide antibody with specificity for this
      region. Binding of insulin and autophosphorylation of the beta-subunit were not
      dependent on O-linked glycosylation, because cells grown in the presence of the
      inhibitor exhibited a normal dose response to insulin. Therefore, the insulin
      receptor contains O-linked oligosaccharides on the NH2-terminal tryptic peptide
      of the beta-subunit, and these O-linked oligosaccharides are not necessary to the
      binding or autophosphorylation function of the receptor.

PMID- 1991571
TI  - Risk factors for development of diabetic nephropathy and retinopathy in Jewish
      IDDM patients.
AB  - Risk factors associated with diabetic microvascular complications, with special
      reference to ethnic origin, were looked for in 231 young Jewish insulin-dependent
      diabetes mellitus (IDDM) patients with duration of diabetes greater than or equal
      to 10 yr. Median age at diagnosis of diabetes was 9.2 yr (range 0.04-26.2 yr),
      and median duration of the disease was 15.3 yr (range 10.0-37.2 yr). Sixty-three
      percent of the patients were Ashkenazi Jews, and 37% were non-Ashkenazi Jews.
      HbA1 was evaluated every 3 mo in the last 10 yr of follow-up, and albumin
      excretion rate was tested in three 24-h urine collections. Direct and indirect
      ophthalmoscopy was performed every year since diagnosis of diabetes, and if
      retinal pathology was suspected, color photographs were taken. Microalbuminuria
      was detected in 31% and macroalbuminuria in 7% of the patients. Nonproliferative
      and proliferative retinopathy was found in 44 and 12% of the patients,
      respectively. On logistic regression analysis, two variables were significantly
      and independently associated with diabetic nephropathy--non-Ashkenazi origin and
      mean HbA1 values over the first 5 of 10 yr of follow-up. Variables significantly
      and independently related to diabetic retinopathy were non-Ashkenazi origin, mean
      HbA1 values over the last 10 yr of follow-up, and duration of diabetes. Because
      non-Ashkenazi Jews in Israel are of lower socioeconomic status than Ashkenazi
      Jews, we stratified our patients according to their socioeconomic parameters,
      median HbA1 values, and duration of diabetes. Non-Ashkenazi patients were at a
      higher risk to develop complications in all strata.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1991572
TI  - Decreased growth velocity before IDDM onset.
AB  - Diabetes can retard growth. Growth was studied prospectively in 12 nondiabetic
      identical twins aged less than 14 yr and in their co-twins with insulin-dependent
      diabetes mellitus (IDDM) to determine whether changes in growth occur before the
      onset of IDDM. Seven of the 12 nondiabetic twins subsequently developed IDDM; the
      remainder are now unlikely to become diabetic. A significantly reduced growth
      velocity was observed more frequently in the nondiabetic twins (7 of 12) than in
      their diabetic co-twins (1 of 12; P = 0.03). Of the 7 nondiabetic twins who were
      prediabetic, 6 had a reduction in growth velocity to below the 3rd percentile
      before the onset of diabetes compared with 1 of their diabetic co-twins (P =
      0.03). However, only 1 of the 5 nondiabetic twins who did not develop diabetes
      showed a reduction in growth velocity. The nadir of growth in the twins who
      developed diabetes occurred a mean of 1.2 yr before diagnosis (range 0.3-2.3 yr).
      All 7 of the prediabetic twins had islet cell antibodies when first seen, and 3
      had them before they showed either decreased growth velocity or impaired glucose
      tolerance. In 4 prediabetic twins, the decreased growth preceded impaired glucose
      tolerance. The prediabetic twins tested had lower testosterone or estradiol
      levels at the time they showed decreased growth than their diabetic twins. We
      conclude that decreased growth velocity is an early sensitive marker of IDDM.

PMID- 1991573
TI  - Reduced neuroendocrine and symptomatic responses to subsequent hypoglycemia after
      1 episode of hypoglycemia in nondiabetic humans.
AB  - To test the hypothesis that hypoglycemia itself causes reduced neuroendocrine and
      symptomatic responses to subsequent hypoglycemia, we measured those responses
      during clamped hypoglycemia (2.8 mM) on consecutive mornings on two occasions,
      with interval afternoon (1400-1600) hypoglycemia (3 mM) on one occasion and
      interval afternoon euglycemia (5 mM) on the other, in nine nondiabetic humans.
      None of the measured responses were reduced by interval euglycemia. In contrast,
      plasma epinephrine (P less than 0.005), glucagon (P less than 0.005), pancreatic
      polypeptide (P less than 0.01), cortisol (P less than 0.02), and total (P less
      than 0.001), neurogenic (P less than 0.001) and neuroglycopenic (P less than
      0.05) symptom responses to morning hypoglycemia were reduced after interval
      afternoon hypoglycemia. Thus, a single episode of hypoglycemia caused a
      generalized reduction of the neuroendocrine and symptomatic responses to
      subsequent hypoglycemia, a finding that may be important to the pathogenesis of
      iatrogenic hypoglycemia in insulin-dependent diabetes mellitus.

PMID- 1991574
TI  - Effects of exercise training and dietary manipulation on insulin-regulatable
      glucose-transporter mRNA in rat muscle.
AB  - Both exercise training and dietary manipulation (increasing omega-3/omega-6 fat
      ratio) can ameliorate insulin resistance caused by a high-fat diet in rats. We
      determined whether alterations in the expression of the insulin-regulatable (IR)
      and/or HepG2 glucose-transporter (GT) mRNAs were similarly affected. There was a
      significantly higher level of IRGT mRNA in skeletal muscle from exercise-trained
      versus sedentary high-fat-fed rats (27% increase, P less than 0.01). This
      difference is consistent with previously reported increases in muscle insulin
      mediated glucose uptake. Skeletal muscle HepG2GT mRNA was too low to detect any
      training effect, but there was a tendency toward higher levels with training in
      cardiac muscle. In contrast, dietary manipulation, previously shown to lead to a
      much greater increase (100-300%) in muscle insulin-mediated glucose uptake, did
      not change IRGT or HepG2GT mRNA in skeletal muscle or heart. Thus, both dietary
      manipulation and exercise training increase insulin-stimulated glucose uptake in
      skeletal muscle, but only exercise training increases IRGT mRNA. Therefore,
      exercise training apparently increases GT production, whereas dietary
      manipulation improves glucose transport in skeletal muscle by other mechanisms.

PMID- 1991576
TI  - Influence of protease on inhibitory and stimulatory effects of interleukin 1 beta
      on beta-cell function.
AB  - To elucidate the putative role of proteases in the action of interleukin 1 beta
      (IL-1 beta) on pancreatic beta-cells, we studied the effects on islet function of
      different protease inhibitors when added together with recombinant IL-1 beta to
      isolated rat pancreatic islets. It was found that the trypsin inhibitor N alpha-p
      tosyl-L-lysine chloromethyl ketone (TLCK) counteracted the acute stimulatory
      effects of IL-1 beta on islet glucose oxidation, insulin release, and
      biosynthesis. TLCK also partially or completely counteracted the long-term
      inhibitory effects of IL-1 beta on islet glucose oxidation, insulin biosynthesis,
      content, and release. This protease inhibitor also counteracted IL-1 beta-induced
      beta-cell cytotoxicity as assessed by DNA content measurements. Of the other
      group-specific protease inhibitors investigated, only N-tosyl-L-phenylalanine
      chloromethyl ketone, N alpha-p-tosyl-L-arginine methyl ester, and
      chloromercuriphenylsulfonic acid were found to partially protect against IL-1
      beta action. We concluded that protease activation, putatively a serine protease,
      may be an early and perhaps primary event in the action of IL-1 beta on beta
      cells.

PMID- 1991575
TI  - Influence of dietary fat composition on development of insulin resistance in
      rats. Relationship to muscle triglyceride and omega-3 fatty acids in muscle
      phospholipid.
AB  - High levels of some but not all dietary fats lead to insulin resistance in rats.
      The aim of this study was to investigate the important determinants underlying
      this observation. Insulin action was assessed with the euglycemic clamp. Diets
      high in saturated, monounsaturated (omega-9), or polyunsaturated (omega-6) fatty
      acids led to severe insulin resistance; glucose infusion rates [GIR] to maintain
      euglycemia at approximately 1000 pM insulin were 6.2 +/- 0.9, 8.9 +/- 0.9, and
      9.7 +/- 0.4 mg.kg-1. min-1, respectively, versus 16.1 +/- 1.0 mg.kg-1.min-1 in
      chow-fed controls. Substituting 11% of fatty acids in the polyunsaturated fat
      diet with long-chain omega-3 fatty acids from fish oils normalized insulin action
      (GIR 15.0 +/- 1.3 mg.kg-1.min-1). Similar replacement with short-chain omega-3
      (alpha-linolenic acid, 18:3 omega 3) was ineffective in the polyunsaturated diet
      (GIR 9.9 +/- 0.5 mg.kg-1.min-1) but completely prevented the insulin resistance
      induced by a saturated-fat diet (GIR 16.0 +/- 1.5 mg.kg-1.min-1) and did so in
      both the liver and peripheral tissues. Insulin sensitivity in skeletal muscle was
      inversely correlated with mean muscle triglyceride accumulation (r = 0.95 and
      0.86 for soleus and red quadriceps, respectively; both P less than 0.01).
      Furthermore, percentage of long-chain omega-3 fatty acid in phospholipid measured
      in red quadriceps correlated highly with insulin action in that muscle (r =
      0.97). We conclude that 1) the particular fatty acids and the lipid environment
      in which they are presented in high-fat diets determine insulin sensitivity in
      rats; 2) impaired insulin action in skeletal muscle relates to triglyceride
      accumulation, suggesting intracellular glucose-fatty acid cycle involvement; and
      3) long-chain omega-3 fatty acids in phospholipid of skeletal muscle may be
      important for efficient insulin action.

PMID- 1991577
TI  - Intermolecular phosphorylation of insulin receptor as possible mechanism for
      amplification of binding signal.
AB  - Clustering of cell-surface insulin receptors has led to the speculation that
      intermolecular phosphorylation of unoccupied receptors catalyzed by ligand
      occupied receptors within the cluster could be a mechanism by which the insulin
      binding signal is amplified. We examined whether insulin receptors can be
      phosphorylated by an intermolecular mechanism. In this study, we used highly
      purified insulin receptors isolated from rat liver plasma membranes and human
      placental membranes. Rat liver insulin receptors were "activated" by incubation
      with 10 nM insulin in the presence of ATP. Subsequent to removal of insulin by
      immunodepletion, these receptors were used as an enzyme source to study
      phosphorylation of unphosphorylated "substrate" human receptors. Initially, we
      found no evidence that the addition of activated rat receptors increased
      phosphorylation of human receptors, when assessed by immunoprecipitation with a
      human-specific monoclonal antibody. To examine the possibility that these
      negative results were due to insufficient receptor concentration, activated human
      receptors were mixed with unphosphorylated substrate receptors at concentrations
      up to 60 micrograms/ml. In this study, we found that addition of activated
      receptors resulted in increased phosphorylation of the substrate receptors at the
      highest concentrations employed. These are the first data indicating that insulin
      receptors per se are capable of intermolecular phosphorylation. In vivo, this
      could be the initial step in amplifying the insulin-binding signal.

PMID- 1991579
TI  - Age discrimination in NIH peer review.

PMID- 1991578
TI  - Molecular mapping of human band 3 anion transport regions using synthetic
      peptides.
AB  - Band 3 is a ubiquitous membrane transport protein found in Golgi, mitochondrial,
      nuclear, and cell membranes. It is the most heavily used anion transport system
      in the body because it is responsible for CO2 exchange in all tissues and organs
      and for acid-base balance. The anion transport regions are mapped along the band
      3 molecule using synthetic peptides (pep) from extracellular regions of band 3
      and/or suspected anion transport regions. Assays include anion
      transport/inhibition and immunoblotting with anti-idiotypic antibodies to a
      transport inhibitor. Results indicate that anion binding/transport regions of
      band 3 reside within residues 549-594, (588-594 being the most active) and 804
      839 (822-839 being the most active), and 869-883. Pep-COOH (residues 812-827),
      which is part of senescent cell antigen, is an anion binding site with most of
      the activity localized to residues 813-818 (the six amino acids on the amino side
      of pep-COOH). The stilbene disulfonate inhibitors of transport bind to peptide
      812-830, and possibly peptides 788-805 and 800-818, as determined with anti
      idiotypic antibodies. Residues 538-554, which have been reported to be a
      transport segment of band 3, do not bind sulfate. Band 3 external loops
      containing residues 539-553 and 812-830, and internal segments containing
      residues 588-594 and 869-883, are in close spacial proximity in the membrane. The
      contribution of lysine and/or arginine to anion transport is examined by
      synthesizing peptides in which glycines or arginines are substituted for lysines
      or arginines. Lysines can contribute to anion binding but are not required.

PMID- 1991580
TI  - Current trends in mapping human genes.
AB  - The human is estimated to have at least 50,000 expressed genes (gene loci). Some
      information is available concerning about 5000 of these gene loci and about 1900
      have been mapped, i.e., assigned to specific chromosomes (and in most instances
      particular chromosome regions). Progress has been achieved by a combination of
      physical mapping (e.g., study of somatic cell hybrids and chromosomal in situ
      hybridization) and genetic mapping (e.g., genetic linkage studies). New methods
      for both physical and genetic mapping are expanding the armamentarium. The
      usefulness of the mapping information is already evident; the spin-off from the
      Human Genome Project (HGP) begins immediately. The complete nucleotide sequence
      is the ultimate map of the human genome. Sequencing, although already under way
      for limited segments of the genome, will await further progress in gene mapping,
      and in particular creation of contig maps for each chromosome. Meanwhile the
      technology of sequencing and sequence information handling will be developed. It
      is argued that the HGP is a new form of coordinated, interdisciplinary science;
      that its primary objective must be seen as the creation of a tool for biomedical
      research--a source book that will be the basis of study of variation and function
      for a long time; that the impact on scientist training will be salutary by
      relieving graduate students of useless drudgery and by training scientists
      competent in both molecular genetics and computational science; and that the
      funding of the HGP will have an insignificant negative effect on science funding
      generally, and indeed may have a beneficial effect through economy of scale and a
      focusing of attention on the excitement of biology and medical science.

PMID- 1991582
TI  - The human genome initiative.

PMID- 1991581
TI  - The Human Genome Project: a paradigm for information management in the life
      sciences.
AB  - The major product of the Human Genome Project will be a series of linked data
      sets containing the genetic and physical location of all genes on each
      chromosome, plus the complete nucleotide sequence of the genome for humans and
      several model organisms. Here we summarize the current status of attempts to
      collect, analyze, and distribute this information in an electronically accessible
      form. Although formidable problems remain to be solved in the acquisition and
      adequate representation of the genetic, physical, and biological data, this
      project is a model for the rapid dissemination of genome and related information
      in biology and medicine.

PMID- 1991583
TI  - DNA sequencing: present limitations and prospects for the future.
AB  - As the human genome program gets under way, we examine the progress made since
      the first human genome meeting in Santa Cruz in 1985. The lessons of the last 5
      years demonstrate that progress has been much slower than anticipated. The new
      technology being developed in 1985 was fluorescent sequencing and multiplexing.
      These techniques are now established, but they still have to produce a
      substantial sequence to rival those determined by conventional technology.
      Inspection of the EMBL and GenBank databases shows few large sequences have been
      determined and that there is a large discrepancy between what is theoretically
      possible and what has been achieved so far.

PMID- 1991584
TI  - Applications of the polymerase chain reaction to genome analysis.
AB  - The objectives of the Human Genome Project are to create high-resolution genetic
      and physical maps, and ultimately to determine the complete nucleotide sequence
      of the human genome. The result of this initiative will be to localize the
      estimated 50,000-100,000 human genes, and acquire information that will enable
      development of a better understanding of the relationship between genome
      structure and function. To achieve these goals, new methodologies that provide
      more rapid, efficient, and cost effective means of genomic analysis will be
      required. From both conceptual and practical perspectives, the polymerase chain
      reaction (PCR) represents a fundamental technology for genome mapping and
      sequencing. The availability of PCR has allowed definition of a technically
      credible form that the final composite map of the human genome will take, as
      described in the sequence-tagged site proposal. Moreover, applications of PCR
      have provided efficient approaches for identifying, isolating, mapping, and
      sequencing DNA, many of which are amenable to automation. The versatility and
      power provided by PCR have encouraged its involvement in almost every aspect of
      human genome research, with new applications of PCR being developed on a
      continual basis.

PMID- 1991585
TI  - The human genome initiative. A view from the South.

PMID- 1991586
TI  - European approach to the Human Gene Project.
AB  - In the history of gene mapping, which extends through most of the present
      century, Europe has played an important role. This has continued during the
      evolution of the 10 International Human Gene Mapping Workshops that have been
      held in seven different countries since 1973. Nationally coordinated programs
      have been a recent development, and several European countries, including the
      United Kingdom and Italy, have followed the lead of the United States in
      investing substantial sums of money in research on the human genome. In addition,
      the European Community has launched a multinational program of research on Human
      Genome Analysis to complement the various national initiatives. The particular
      approach in Europe has been to support those in the field by establishing
      resource centers for distributing biomaterials and accessing databases, by
      assisting in the training of scientists, and by funding programs of research
      directed at present needs in both physical and genetic mapping.

PMID- 1991587
TI  - Human genome efforts in Japan.
AB  - Some project-oriented biosciences have been promoted cooperatively by three
      governmental agencies in Japan: the Ministry of Education, Science and Culture,
      the Ministry of Health and Welfare, and the Science and Technology Agency. All
      three agencies have increased their budgetary requests for human genome analyses
      for FY 1991. The Panel on Life Sciences (chaired by Dr. W. Mori, former president
      of the University of Tokyo) of the Science and Technology Council of Japan which
      is chaired by the Prime Minister has decided to organize a working group to
      suggest how best to coordinate efforts in human genome analyses in Japan. The
      genome project was initially promoted by the Science and Technology Agency
      through a program for the design and construction of automated machines for DNA
      sequencing. Work is ongoing at the Institute of Physical and Chemical Research to
      integrate, by system engineering, instruments that can separate DNA fragments,
      perform plaque selection, carry out dideoxy reaction, and read the resulting DNA
      sequence. However, scientists now realize the enormity of the tasks of compiling
      DNA sequence data and of mapping the genes and fragments obtained, and efforts
      are being made to solve these problems. Academic societies have organized
      symposia to promote general interest in this subject. The most important way for
      Japan to contribute to research on human genome analyses, however, may be in the
      evaluation of supporting mechanisms (technical assistance and research resources)
      and in the recognition and preparation of the transition of biology to a big
      science approach.

PMID- 1991588
TI  - First moves of the USSR Human Genome Project.

PMID- 1991589
TI  - HUGO: the Human Genome Organization.

PMID- 1991590
TI  - The human genome initiative. All our collective ingenuity will be needed.

PMID- 1991591
TI  - The human genome initiative. Some problems with a crash program.

PMID- 1991592
TI  - The Genome Project and human health.

PMID- 1991593
TI  - The human genome initiative. There are two large questions.

PMID- 1991594
TI  - Immunogold labeling of perforin and serine esterases in granulated metrial gland
      cells.
AB  - Cytotoxic T lymphocytes (CTL) and natural killer (NK) cells are cytolytic
      lymphocytes known to produce a pore-forming protein, named perforin or cytolysin,
      that lyses target cells by creating large pores on the target plasma membrane.
      Besides perforin, the granules of CTL and NK cells contain a family of serine
      esterases. Perforin has also been localized in granulated metrial gland (GMG)
      cells of the murine embryo implantation site by light microscopic immunostaining.
      Ultrastructural immunogold labeling with antibodies against perforin and a serine
      esterase (MTSP 1 or granzyme A) shows that GMG cells contain both perforin and
      serine esterases in the fine granular matrix of their granules. Perforin has been
      located in all of the granules, whereas gold particles corresponding to serine
      esterases have been found in most of the granules. Results from the double
      immunogold technique indicate that perforin and serine esterases colocalize to
      most of the same granules in GMG cells. This study supports the view that GMG
      cells are related to cytolytic lymphocytes.

PMID- 1991595
TI  - Origins of the Human Genome Project.
AB  - The Human Genome Project has become a reality. Building on a debate that dates
      back to 1985, several genome projects are now in full stride around the world,
      and more are likely to form in the next several years. Italy began its genome
      program in 1987, and the United Kingdom and U.S.S.R. in 1988. The European
      communities mounted several genome projects on yeast, bacteria, Drosophila, and
      Arabidospis thaliana (a rapidly growing plant with a small genome) in 1988, and
      in 1990 commenced a new 2-year program on the human genome. In the United States,
      we have completed the first year of operation of the National Center for Human
      Genome Research at the National Institutes of Health (NIH), now the largest
      single funding source for genome research in the world. There have been dedicated
      budgets focused on genome-scale research at NIH, the U.S. Department of Energy,
      and the Howard Hughes Medical Institute for several years, and results are
      beginning to accumulate. There were three annual meetings on genome mapping and
      sequencing at Cold Spring Harbor, New York, in the spring of 1988, 1989, and
      1990; the talks have shifted from a discussion about how to approach problems to
      presenting results from experiments already performed. We have finally begun to
      work rather than merely talk. The purpose of genome projects is to assemble data
      on the structure of DNA in human chromosomes and those of other organisms. A
      second goal is to develop new technologies to perform mapping and sequencing.
      There have been impressive technical advances in the past 5 years since the
      debate about the human genome project began. We are on the verge of beginning
      pilot projects to test several approaches to sequencing long stretches of DNA,
      using both automation and manual methods. Ordered sets of yeast artificial
      chromosome and cosmid clones have been assembled to span more than 2 million base
      pairs of several human chromosomes, and a region of 10 million base pairs has
      been assembled for Caenorhabditis elegans by a collaboration between Washington
      University and the Medical Research Council laboratory in Cambridge, U.K. This
      project is now turning to sequencing C. elegans DNA as a logical extension of
      this work. These are but the first fruits of the genome project. There is much
      more to come.

PMID- 1991596
TI  - Effect of retinoic acid and apo-RBP on serum retinol concentration in acute renal
      failure.
AB  - We recently demonstrated a rapid up-regulation of serum retinol-retinol binding
      protein-transthyretin concentration in rats with short-term acute renal failure.
      We examine the effect of retinoic acid and apo-retinol binding protein (apo-RBP)
      on the up-regulation of serum retinol in renal failure. Injection of retinoic
      acid (10 micrograms) into rats with acute renal failure or sham-operated rats
      increased circulatory retinoic acid concentration 29-fold within 2 h but did not
      influence serum retinol concentration in either group. Injection of a large dose
      of retinoic acid (100 micrograms) decreased serum retinol concentration in rats
      with acute renal failure (19%) and sham-operated rats (29%). These results
      suggest that changes in serum retinoic acid concentration within the near
      physiological range have no effect on regulation of hepatic retinol release.
      Injection of a large dose of retinoic acid may depress serum retinol indirectly
      via a retinol sparing effect in target tissues. In rats with renal failure the
      serum retinol concentration, elevated 44-52% above that of sham-operated
      controls, was also increased to 70-164% above controls by the injection of 52-63
      micrograms of apo-RBP. This suggests that circulatory apo-RBP can up-regulate
      serum retinol. Circulatory apo-RBP may be a positive physiological feedback
      signal from peripheral tissues for hepatic release of retinol.

PMID- 1991597
TI  - Evaluation of the esophagus with a marshmallow bolus: clarifying the cause of
      dysphagia.
AB  - We reviewed the radiographic examinations of the esophagus and medical records in
      117 patients (55 women and 62 men; mean age, 52 years) in which a marshmallow
      bolus was also given. A one-third to one-half piece of a standard marshmallow was
      used with a mean size of 23 mm (+/- 4.5 mm SD) measured in vivo. In 62 patients
      with no intrinsic structural narrowing of the esophagus, impaction occurred in
      only seven (11%). Four of these patients had an esophageal motility disorder, and
      three had a previous Nissen fundoplication. The remaining 55 patients had lower
      esophageal mucosal rings (47) or peptic strictures (8). Marshmallow impaction was
      seen in 27 of 47 rings (57%) and was inversely related to ring size, and in six
      of eight strictures (75%). Also, impaction was related to the ratio of bolus size
      to ring caliber, and invariably occurred when this ratio was greater than 1.5.
      Dysphagia was the presenting complaint in 76 (65%) patients, but was found
      equally in those without intrinsic narrowing and in those with ring or stricture.
      However, dysphagia was reproduced by the marshmallow bolus only in patients with
      esophageal narrowing or abnormal motility.

PMID- 1991598
TI  - Chicken bone lodged in the upper esophagus: CT findings.
AB  - The authors report a case of a chicken bone lodged in the esophagus at the
      cervicothoracic junction. Both the radiographic and endoscopic examinations of
      the esophagus had failed to detect the ingested bone, but computed tomography
      (CT) demonstrated it as an opaque fragment penetrating the esophageal wall.

PMID- 1991599
TI  - Postgastrostomy tube deformity on upper GI series.
AB  - Three cases are presented in which a focal concave deformity occurred along the
      greater curvature of the stomach on upper gastrointestinal (GI) series. These
      patients all had recent removal of a surgically placed gastrostomy tube from a
      similar location. This deformity appears to be related, at least in part, to
      invaginated gastric mucosa intentionally produced during surgical gastrostomy
      tube placement. This association and appearance should be noted as it may mimic
      other lesions.

PMID- 1991600
TI  - Duodenal adenocarcinoma in Crohn's disease of the small bowel: a case report.
AB  - A 47-year-old woman with a 15-year history of Crohn's disease (CD) developed an
      adenocarcinoma of the duodenum. The preoperative diagnosis was suspected on
      radiologic and endoscopic examination and confirmed histologically.

PMID- 1991601
TI  - Crohn's disease of the small intestine with polypoid configuration.
AB  - We describe three patients with Crohn's disease of the small intestine with a
      polypoid configuration. In two patients, the polypoid masses were the only
      radiologic abnormalities and were suggestive of jejunoileal lymphoma and terminal
      ileal adenomas. The diagnosis of Crohn's disease was established only at
      laparotomy. In the third patient, a polypoid mass simulating a sessile adenoma
      was seen along with other typical features of ileitis and was recognized
      preoperatively as a manifestation of the ileitis. The resected ileal segments of
      all three patients showed mural thickening, luminal narrowing and distortion, and
      mucosal ulceration and fissuring. The asymmetry of the mural thickening and the
      resultant luminal narrowing simulated sessile polyps to which mucosal ulceration
      and fissuring gave a lobulated appearance.

PMID- 1991602
TI  - Peutz-Jeghers syndrome: CT and US demonstration of small bowel polyps.
AB  - A family affected with Peutz-Jeghers syndrome is reported with an emphasis on
      radiological findings. A patient showed extensive pigmentation around the lips,
      buccal mucosa, and nose. Another showed prolonged transient intussusception of a
      jejunal loop on barium meal examination, and massive rectal bleeding. In this
      patient, small bowel polyps could also be seen on ultrasonography (US) and
      computed tomography (CT). On CT several polyps, up to 3 cm in size, were detected
      along with a "carpeting" pattern of several loops presumably caused by multiple
      small polyps.

PMID- 1991604
TI  - Small bowel perforation during enteroclysis.
AB  - Small bowel perforation with massive intraperitoneal leakage of barium occurred
      during the performance of enteroclysis in a 72-year-old woman. It is postulated
      that an ischemic segment of the partially obstructed ileum had ruptured because
      of rapid intraluminal flow of contrast material and increased abdominal pressure
      when the patient was rotated to a prone position.

PMID- 1991603
TI  - Diverticulitis of the jejunum: clinical and radiological features.
AB  - This article describes three cases of jejunal diverticulitis in elderly women,
      who had presented with pain and tenderness in the periumbilical region or the
      left side of the abdomen, low-grade fever, anemia, and weight loss. The findings
      were initially attributed to possible inflammatory or neoplastic lesions of the
      colon. However, gastrointestinal barium studies and computed tomography (CT) of
      the abdomen proved crucial in establishing the preoperative diagnosis of jejunal
      diverticulitis and its associated abscess in the adjacent mesentery or abdominal
      wall. The clinical and radiological manifestations of this uncommon entity are
      herein presented along with a brief review of the pertinent literature.

PMID- 1991605
TI  - Pitfalls of a 99mTc-RBC bleeding study due to gallbladder and ileal-loop
      visualization.
AB  - A series of 99mTc-labeled red blood cell (RBC) scintigrams in a patient with a
      past history of radiation proctitis demonstrated incidental findings of
      gallbladder activity, probably related to multiple blood transfusions and renal
      failure. Variable activity in an ileal-loop urinary diversion simulating bowel
      pooling was also noted. Thus, difficulties encountered in scan interpretation are
      presented.

PMID- 1991606
TI  - Ultrasound in detection of portal venous gas in adults.
AB  - Three patients with sonographically demonstrated portal venous gas are presented.
      Two patients were also studied using computed tomography (CT). Both techniques
      had superior sensitivity compared to plain radiographs. Scattered echogenic
      patches in the liver parenchyma, and centrifugal flow of echogenic patches in the
      portal vein and its branches, are typical ultrasound findings of portal vein gas.
      Evaluation of ultrasound findings and coordination with clinical history
      differentiate portal vein gas from biliary gas.

PMID- 1991607
TI  - Spontaneous portal venous gas in a patient with Crohn's ileocolitis.
AB  - In a 70-year-old man with Crohn's ileocolitis who presented with a sudden fever,
      ultrasound and computed tomographic (CT) examinations showed hepatic portal
      venous gas (HPVG). Abdominal plain film was normal. The course was benign with
      medical management. The authors review previous cases of portal vein gas in
      intestinal inflammatory diseases.

PMID- 1991608
TI  - CT appearance of the Roux limb following choledochojejunostomy in liver
      transplantation.
AB  - Choledochojejunostomy in Roux-en-Y is a frequent form of biliary reconstruction
      in liver transplants. On computed tomography (CT), fluid in the Roux limb may
      simulate a fluid collection. We studied the CT appearance of the Roux jejunal
      limb in 25 normal and complicated liver transplant patients. The Roux limb was
      identified in 21 (84%) of 25 cases. Most frequently useful features were
      characteristic location, continuous tubular appearance, biliary stent, "bull's
      eye" appearance, and gas in the loop. Two of 18 normal Roux loops were initially
      suspected of being abscesses and one gas-containing abscess was initially
      mistaken for the Roux limb. In five of seven patients with complications (four
      abscesses, two bile leaks, one anastomotic hemorrhage), identification of the
      Roux limb was possible and was useful in interpreting CT scans. Knowledge of the
      appearance of the normal and abnormal Roux limb is essential for proper
      interpretation of CT scans in liver transplant patients.

PMID- 1991609
TI  - Variations of common bile duct diameter after endoscopic sphincterotomy.
AB  - Diameters of the common bile duct (CBD) and common hepatic duct (CHD) were
      measured before and after endoscopic sphincterotomy (EPT) in 100 patients. There
      was a significant reduction of the lumen diameter in both the CBD and CHD (p less
      than 0.01) after EPT. A comparison between 32 patients without symptoms (such as
      pain, residual stones, and elevated levels of liver enzymes) and 19 patients with
      remaining symptoms after EPT, showed a statistically significant reduction in
      both CBD and CHD diameters (p less than 0.001) in the former group, and no
      statistically proven changes in the diameters in the latter group, since a change
      of less than 1.5 mm was not considered significant. Therefore, the absence of a
      reduction or a dilatation of the diameter of the CBD after EPT may suggest that
      these patients may have persisting complaints after EPT. Measurements on models
      (phantoms) show that body position of the patient during endoscopic retrograde
      cholangiopancreatography (ERCP) has little and negligible influence on the
      measured diameters of the CBD and CHD.

PMID- 1991610
TI  - Oral cholecystography: comparison of conventional screen-film with
      photostimulable imaging plate radiographs.
AB  - Oral cholecystography was performed on ultrasonically proven cases of
      cholelithiasis. The conventional screen/film system and computed radiography (CR)
      using the imaging plate were used under practically identical conditions. The
      diagnostic accuracy of the two techniques was assessed objectively, and the image
      quality was assessed subjectively. The CR image proved to be better than the
      conventional screen/film image, even with the low-dose exposure. This paper
      describes our experience in the area of the biliary tract system with CR - a
      digital radiographic system using photostimulable phosphor.

PMID- 1991612
TI  - Microcystic adenoma of the pancreas: report on four cases and review of the
      literature.
AB  - Four cases of microcystic adenoma of the pancreas, including ultrasonographic
      (US) and computed tomographic (CT) data, are described. These tumors generally
      present as large, well-delimited pancreatic masses whose multicystic nature is
      readily evidenced on postcontrast CT scans. While the presence of cysts less than
      2 cm in diameter and a central, star-like calcification are very specific, the
      frequency of atypical forms generally justifies exploratory surgery.

PMID- 1991613
TI  - Percutaneous fine-needle aspiration biopsy of the pancreas resulting in death.
AB  - Percutaneous fine-needle aspiration biopsy of the pancreas presents a slightly
      higher risk of complications than does biopsy of other abdominal organs,
      occasionally leading to death. In the case we discuss, computed tomographic (CT)
      guided percutaneous fine-needle aspiration biopsy of a pseudolesion of the
      uncinate process resulting in hemorrhagic pancreatitis and the death of the
      patient within 1 week of the procedure.

PMID- 1991611
TI  - Cystic tumors of the pancreas: evaluation by ultrasonography and computed
      tomography.
AB  - The personal series of 30 cystic tumors of the pancreas [12 serous cystic tumors
      (SCT) and 18 mucinous cystic tumors (MCT)] is presented. All neoplasms were
      evaluated with ultrasonography (US) 28 of 30 with computed tomography (CT); the
      tumoral histotype could be correctly defined in 73% of cases (seven of 12 SCT and
      15 of 18 MCT). Percutaneous fine-needle aspiration (FNA) with diagnostic aims
      (preparation of cytological smears and/or biochemical assays) was performed in
      only 10 of 30 cases, yielding a 100% sensitivity; on the whole, the combined use
      of imaging modalities and FNA allowed correct characterization of the cystic
      tumors in 27 of 30 cases (90%). The usefulness of a precise diagnostic workup of
      these neoplasms is emphasized, due to their prognostic and therapeutic outcome.

PMID- 1991614
TI  - Pancreatic pseudocyst in a gastrectomized patient: treatment with internalized
      endoprosthesis.
AB  - Direct percutaneous drainage of pancreatic pseudocysts in communication with the
      duct of Wirsung can lead to pancreaticocutaneous fistula. These patients are
      safely treated with the percutaneous transgastric approach. In a gastrectomized
      patient who developed a pseudocyst, we percutaneously placed in internal
      endoprosthesis from the duct of Wirsung to the afferent loop and gastric pouch.

PMID- 1991615
TI  - Intraobserver variation in the radiological measurement of the anorectal angle.
AB  - Seven experts drew the rectal axes of 18 representative proctographic images on
      two occasions, with a 1-year interval, in order to assess intraobserver variation
      in the determination of the anorectal angle (ARA). Intraobserver variation (6%)
      and interobserver variation (17%) were smallest when the central rectal axis was
      used to determine the ARA. A strong relation was found between inter- and
      intraobserver variation (r = 0.77). Intraobserver variation tended to be rather
      small for pictures made during straining, but a relation with the magnitude of
      the ARA was not found. Although none of the seven experts could reproduce the
      rectal axes with less than or equal to 10% variation in all 18 pictures,
      redrawing of the central rectal axis delivered less than or equal to 10%
      variation in 86% of determinations. It is concluded that intraobserver variation
      is influenced by the expertise of the investigator, the method of analysis, and
      the anorectal configuration to be analyzed. Radiologic assessment of the ARA may
      yield reliable data on the dynamics of the anorectum if performed by a single
      investigator on x-ray films that allow confident analysis.

PMID- 1991616
TI  - CT diagnosis of cecal herniation through the foramen of Winslow.
AB  - The computed tomographic (CT) appearance of a case of cecal herniation through
      the foramen of Winslow is described. This is an extremely uncommon type of
      internal hernia, and, to the best of our knowledge, its CT appearance has not
      been reported. Its recognition is important to both establish a preoperative
      diagnosis and to distinguish it from a lesser sac collection or abscess.

PMID- 1991617
TI  - Comments about Glisson's capsule phleboliths and portal vein thrombosis.

PMID- 1991618
TI  - The medicare squeeze tightens.

PMID- 1991619
TI  - MRI, CT, SPECT, PET: their use in diagnosing dementia.
AB  - The differential diagnosis of the dementia syndrome may pose a difficult clinical
      problem, since the most common dementia, Alzheimer's disease (AD), is marked by
      normal laboratory tests. Neuroimaging has played an important role in evaluating
      the demented patient, and its uses are growing. Computed tomography (CT) is
      useful for excluding reversible and treatable causes of dementia, such as
      subdural hematoma and tumor. More recently, magnetic resonance imaging (MRI) has
      improved our ability to diagnose vascular disease and may show the presence of
      cerebral infarcts and white matter disease not visible on CT. Single photon
      emission computed tomography (SPECT) and positron emission tomography (PET),
      techniques that visualize such cerebral functions as glucose metabolism and blood
      flow, may provide positive evidence supportive of the diagnosis of AD.

PMID- 1991620
TI  - The renally compromised older hypertensive: therapeutic considerations.
AB  - Although the slow progression of renal insufficiency caused by aging does not
      usually reach the clinical disease level, nephron loss may be accelerated by the
      concomitant presence of hypertension and renal artery atherosclerosis. Treatment
      of hypertension and correction of other risk factors promoting atherosclerosis is
      appropriate in the elderly. Consideration should be given to a search for
      reversible causes of renal functional deterioration in elderly patients,
      particularly in those with increasingly refractory hypertension. In the
      uncomplicated elderly hypertensive, renal function appears to be adequately
      preserved if blood pressure is well controlled, although there may be a subset in
      whom factors other than blood pressure itself, such as glomerular hemodynamic
      disturbances, promote progressive renal dysfunction.

PMID- 1991621
TI  - Pneumonia: update on diagnosis and treatment.
AB  - Pneumonia is the most common infectious disease necessitating hospitalization of
      elderly patients. A number of misconceptions exist regarding the clinical and
      radiological features of pneumonia in elderly patients. Early recognition and
      appropriate therapy can reduce morbidity and enhance survival. This article
      explores the manifestations of pneumonia in the elderly, as well as the
      diagnostic approach and contemporary therapy.

PMID- 1991622
TI  - "These foolish things": reflections on older smokers and drinkers.

PMID- 1991623
TI  - Why aging leads to increased susceptibility to infection.
AB  - The elderly are predisposed to various infections through a multitude of factors.
      Although intrinsic, unalterable defects occur in the aging immune system and
      nonspecific host defenses, there are factors that physician and patient can
      concentrate on to reduce the risk of infection. For example, meticulous attention
      to skin care can reduce the risk of soft tissue infection. Improvement in oral
      hygiene and relief of xerostomia might promote recolonization with normal oral
      flora. Correction of urinary tract obstruction where possible, relying on the use
      of indwelling urinary catheters only when necessary, can significantly reduce the
      risk of UTIs. Medications that impair cognitive function should be prescribed
      judiciously, since they can promote aspiration with subsequent pneumonia,
      xerostomia, and urinary retention. Correction of protein malnutrition may improve
      cell-mediated immunity and skin integrity, thereby reducing the risk of
      infection. The signs and symptoms of infection in the aged may be subtle.
      Therefore, the primary care physician should approach this susceptible population
      with a heightened clinical suspicion, thus expediting possibly life-saving early
      diagnosis and treatment.

PMID- 1991624
TI  - Conversation with ... Fredrick T. Sherman, MD: for physicians treating the
      elderly, what lies ahead?. Interview by Richard L. Peck.

PMID- 1991626
TI  - Twelve hour overnight oesophageal pH monitoring in patients with reflux symptoms.
AB  - Results of continuous 12 hour overnight pH monitoring (duration of pH less than
      4) were reviewed in 112 patients with heartburn or regurgitation, or both, and in
      56 normal subjects. Patients had more reflux than normal subjects. Medically
      controlled patients (n = 51) had less acid reflux than patients who subsequently
      underwent reflux surgery (n = 61), but there was a considerable overlap between
      those two groups. Surgery was followed by a reduction in acid reflux to a value
      similar to that in normal subjects. Patients in whom surgery was deemed to have
      failed had more reflux after the operation than those in whom it was successful,
      but no difference could be found in the preoperative reflux values of these two
      subgroups. Monitoring pH is not of value in selecting candidates for surgery
      since the results are not a good predictor of outcome, but it is useful in the
      objective evaluation of surgical results.

PMID- 1991625
TI  - DNA probes for diagnosis of intestinal infection.

PMID- 1991627
TI  - Provision of facilities for manometry and pH monitoring in the investigation of
      patients with oesophageal disease.

PMID- 1991628
TI  - Bacterial adhesion and Helicobacter pylori.

PMID- 1991629
TI  - Obscure anaemia and hepatic dysfunction in Castleman's disease.

PMID- 1991630
TI  - Role of computed tomography, endoscopy and echoendoscopy in the management of
      alimentary tract lipomas.

PMID- 1991631
TI  - Sedation for upper gastrointestinal endoscopy: results of a nationwide survey.
AB  - A postal questionnaire inquiring about routine sedation and premedication
      practice for upper gastrointestinal endoscopy was sent to 1048 doctors. Of 665
      appropriate returns, 81% were from consultant physicians and surgeons. Most
      endoscopists (90%) reported using an intravenous benzodiazepine for at least
      three quarters of endoscopies and 54% of physicians and 69% of surgeons always
      did so. Midazolam was the intravenous sedative used by a third of all respondents
      and 13% also used an additional intravenous agent, usually pethidine. Over the
      previous two years a total of 119 respiratory arrests, 37 cardiac arrests, and 52
      deaths were identified. Adverse outcomes were reported more frequently by
      consultant physicians, by those who 'titrated' the intravenous sedative, and by
      those who used an additional intravenous agent, but were reported equally
      frequently by endoscopists using midazolam and endoscopists using diazepam. There
      is an urgent need for a prospective study to identify the circumstances and risk
      factors associated with adverse outcomes related to endoscopy.

PMID- 1991632
TI  - Evaluation of endosonography in TN staging of oesophageal cancer.
AB  - Strategies for the treatment of cancer of the oesophagus depend on the tumour
      stage at the time of diagnosis. Resection, the only curative treatment, is
      confined to early tumour stages. Tumours with local infiltration are usually
      unresectable and require palliative treatment. Computed tomography has been
      widely used for preoperative staging but often fails to define this correctly.
      Endoscopic ultrasound allows direct visualisation of the parietal wall and may be
      useful in staging gastrointestinal tumours. In a comparative prospective study,
      52 patients with tumours of the oesophagus were investigated preoperatively both
      by endoscopic ultrasound and computed tomography to determine the stage of tumour
      infiltration and local lymph node involvement. Thirty seven of these patients
      underwent operation, resection, or dissection and entered the study. The
      intraoperative findings or the histopathological assessment, or both, were taken
      as a reference. For all TN stages of oesophageal tumours, correct preoperative
      staging was accomplished by endoscopic ultrasound in 89% for T stage and 69% for
      N stage compared with 51% and 51% respectively by computed tomography (highly
      significant using Fisher's exact test). This study shows that endoscopic
      ultrasound is useful in preoperative TN staging of tumours of the oesophagus.

PMID- 1991633
TI  - Effect of increasing Helicobacter pylori ammonia production by urea infusion on
      plasma gastrin concentrations.
AB  - It has been proposed that the hypergastrinaemia in subjects with Helicobacter
      pylori infection is caused by the action of the ammonia produced by the
      organism's urease activity on the antral G cells. To investigate this hypothesis
      we examined the effect on plasma gastrin of increasing the bacterium's ammonia
      production by infusing urea intragastrically to eight H pylori positive duodenal
      ulcer patients. After a 60 minute control intragastric infusion of dextrose
      solution at 2 ml/minute, a similar infusion containing urea (50 mmol/l) was
      continued for four hours. During the urea infusion, the median gastric juice urea
      concentration rose from 1.1 mmol/l (range 0.3-1.6) to 15.5 mmol/l (range 7.9
      21.3) and this resulted in an increase in the ammonium concentration from 2.3
      mmol/l (range 1.3-5.9) to 6.1 mmol/l (range 4.2-11.9) (p less than 0.01). This
      appreciable rise in ammonia production did not result in any change in the plasma
      gastrin concentration. The experiment was repeated one month after eradication of
      H pylori, at which time the median basal gastrin was 20 ng/l (range 15-25),
      significantly less than the value before eradication (30 ng/l range 15-60) (p
      less than 0.05). On this occasion, the gastric juice ammonium concentration was
      considerably reduced at 0.4 mmol/l (range 0.1-0.9) and the urea infusion did not
      raise the ammonium concentration or change the plasma gastrin concentration. In
      conclusion, augmenting H pylori ammonia production does not cause any early
      change in plasma gastrin.

PMID- 1991634
TI  - Helicobacter pylori infection rates in relation to age and social class in a
      population of Welsh men.
AB  - The seroprevalence of IgG antibodies to Helicobacter pylori was determined using
      a standard enzyme linked immunosorbent assay in a population of 749 randomly
      selected men, aged 30-75 years, from Caerphilly, South Wales. The overall
      prevalence of H pylori was 56.9%, increasing sharply in middle age from 29.8% in
      those aged 30-34 to over 59% in those aged 45 or older (p less than 0.0001). Age
      standardised seroprevalence rates were lowest in combined social class categories
      I and II (49.2%), intermediate in categories IIIN and M (57.5%), and highest in
      categories IV and V (62.2%) (p = 0.01). In those aged 30-34 years, the prevalence
      rate for those in combined social class categories IV and V was 57.9% - double
      the rate for social class categories IIIM and N (28.3%) and five times the
      prevalence rate in those in social class categories I and II (11.1%). These
      differences in the infection patterns of H pylori by social class are consistent
      with patterns of peptic ulcer disease and gastric cancer.

PMID- 1991635
TI  - Dissociation between systemic and mucosal humoral immune responses in coeliac
      disease.
AB  - We examined humoral immunity in coeliac disease as expressed in serum (systemic
      immunity), and in saliva, jejunal aspirate, and whole gut lavage fluid (mucosal
      immunity). The aims were to define features of the secretory immune response (IgA
      and IgM concentrations and antibody values to gliadin and other food proteins
      measured by enzyme linked immunosorbent assay (ELISA)) in active disease and
      remission, and to establish whether secretions obtained by relatively non
      invasive techniques (saliva and gut lavage fluid) can be used for indirect
      measurements of events in the jejunum. Serum, saliva, and jejunal aspirate from
      26 adults with untreated coeliac disease, 22 treated patients, and 28
      immunologically normal control subjects were studied, together with intestinal
      secretions obtained by gut lavage from 15 untreated and 19 treated patients with
      coeliac disease and 25 control subjects. Jejunal aspirate IgA and IgM and gut
      lavage fluid IgM concentrations were significantly raised in patients with
      untreated coeliac disease; the lavage fluid IgM concentration remained higher in
      patients with treated coeliac disease than in controls. Serum and salivary
      immunoglobulin concentrations were similar in the three groups. Patients with
      untreated coeliac disease had higher values of antibodies to gliadin compared
      with treated patients and control subjects in all body fluids tested; these were
      predominantly of IgA and IgG classes in serum, and of IgA and IgM classes in
      jejunal aspirate and gut lavage fluid. Values of salivary IgA antibodies to
      gliadin were significantly higher in untreated coeliacs, though antibody values
      were generally low, with a large overlap between coeliac disease patients and
      control subjects. In treated patients, with proved histological recovery on
      gluten free diet, serum IgA antigliadin antibody values fell to control values,
      though serum IgG antigliadin antibody values remained moderately raised. In
      contrast, there was persistence of secretory antigliadin antibodies in treated
      patients (particularly IgM antibody) in both jejunal aspirate and gut lavage
      fluid. Antibody responses to betalactoglobulin and ovalbumin were similar to
      those for gliadin, including persistence of high intestinal antibody values in
      patients with treated coeliac disease. There was a positive correlation between
      antibody values in jejunal aspirate and gut lavage fluid, but not between saliva
      and jejunal aspirate; thus salivary antibodies do not reflect intestinal humoral
      immunity.

PMID- 1991636
TI  - Autoimmune enteropathy and colitis: is there a generalised autoimmune gut
      disorder?
AB  - Children with protracted diarrhoea, circulating enterocyte autoantibodies, and an
      enteropathy showing features of inappropriate HLA molecule expression on the
      jejunal crypt epithelium, often present with persistent blood and mucus in their
      stools. Eight children with autoimmune enteropathy were investigated for the
      presence of associated colonic disease. Six children with protracted diarrhoea,
      no circulating autoantibodies, and an enteropathy (in five of them) undergoing
      colonoscopy were used as control subjects. In all eight patients, but not in the
      control subjects, there was macroscopic and microscopic evidence of an
      accompanying colitis of variable severity, thus indicating that a more
      generalised intestinal disorder was present, which might affect the whole
      intestine. Aberrant expression of DR molecules on the colonic surface and crypt
      epithelium was also detected. Autoimmunity may play a role in the colitis.

PMID- 1991637
TI  - Mycobacterium paratuberculosis and Crohn's disease.
AB  - The possible aetiological role of Mycobacterium paratuberculosis in Crohn's
      disease was investigated. The immunological response was studied using an enzyme
      linked immunosorbent assay (ELISA), Western blotting, and immunocytochemistry.
      The antibody response to two protoplasmic antigen preparations of M
      paratuberculosis in the sera of patients with inflammatory bowel disease was
      measured by ELISA. IgG and IgM antibodies to these antigens were measured in
      serum samples from 52 patients with Crohn's disease, 15 patients with ulcerative
      colitis, and 41 control patients without inflammatory bowel disease. Although
      there was wide variation in the concentrations of antibody detected, patients
      with Crohn's disease had concentrations that were not significantly different
      from those of the other two groups. In addition, mycobacterial antigens were
      separated by sodium dodecyl sulphate polyacrylamide gel electrophoresis and the
      immune response to each antigen was then examined separately and assayed for IgG
      and IgM in 10 patients from each of the three groups. An indirect peroxidase test
      was also used to detect M paratuberculosis in sections of tissue from 18 patients
      with Crohn's disease and 10 with ulcerative colitis. The results were negative in
      all cases. This study does not support a role for M paratuberculosis in Crohn's
      disease.

PMID- 1991638
TI  - Impaired sulphation of phenol by the colonic mucosa in quiescent and active
      ulcerative colitis.
AB  - Substantial amounts of phenols are produced in the human colon by bacterial
      fermentation of protein. In the colonic mucosa of animals, phenols are
      inactivated predominantly by conjugation with sulphate. The purpose of this study
      was to confirm sulphation of phenols by isolated colonocytes from man and to
      evaluate mucosal sulphation in inflammatory bowel disease using the phenol,
      paracetamol, in rectal dialysis bags. The incubation of paracetamol with
      colonocytes isolated from resected colon specimens (n = 7) yielded a mean (SE)
      value of 7.0 (0.9) mumols/g dry weight of paracetamol sulphate after 60 minutes
      but virtually undetectable values of paracetamol glucuronide. Paracetamol
      sulphate was detected in rectal dialysates from all control subjects, with a mean
      (SE) value of 4.2 (0.8) nmol/hour. Sulphation was significantly impaired (p less
      than 0.01) in 19 patients with active ulcerative colitis (0.6 (0.2) nmol/hour)
      and in 17 patients with ulcerative colitis in remission (1.1 (0.4) nmol/hour).
      Sulphation in eight patients with Crohn's colitis (4.3 (2.1) nmol/hour) was
      similar to that in control subjects. Impairment of the capacity of the mucosa to
      sulphate phenols in quiescent and active ulcerative colitis may pose a metabolic
      burden on colonic epithelial cells, which are continuously exposed to endogenous
      phenols from the colonic lumen.

PMID- 1991639
TI  - Candidacidal activity of Crohn's disease neutrophils.
AB  - The ability of normal and Crohn's disease neutrophils to kill Candida albicans
      has been studied using neutrophils isolated from peripheral blood and suspended
      in phosphate buffered saline at 5 x 10(6) cells per ml. C albicans was grown to a
      stationary phase in broth culture and suspended in phosphate buffered saline at
      10(7) organisms/ml. Neutrophils and Candida were then incubated together at 37
      degrees C in a shaking water bath in the presence of fresh serum. At 30 and 60
      minutes samples were withdrawn, neutrophils lysed, and Candida survival assessed
      by colony counting. Results were compared with control suspensions of Candida
      incubated with serum alone. After 30 and 60 minutes in the presence of autologous
      serum normal neutrophils had killed significantly more Candida than Crohn's
      disease neutrophils (mean (SD) 61.0 (16.7)% v 40.5 (16.2)% at 30 minutes, p less
      than 0.0001; 83.2 (7)% v 70.8) 16)% at 60 minutes, p less than 0.005). The
      results did not alter significantly when normal neutrophils were incubated with
      Candida in the presence of Crohn's disease serum instead of normal serum. When
      Crohn's disease neutrophils were incubated with Candida in the presence of normal
      serum instead of autologous serum there was some improvement in candidacidal
      ability at 30 minutes (48.9 (20.6)% v 40.5 (16.2)%, p less than 0.03) but not at
      60 minutes. Phagocytosis, measured using a radiometric assay, was normal.
      Neutrophils from patients with Crohn's disease have an impaired ability to kill
      this granuloma provoking organism. It is not due to serum inhibitors or defective
      phagocytosis.

PMID- 1991640
TI  - Alcohol consumption in patients with colorectal adenomatous polyps.
AB  - The risk of developing colorectal adenomatous polyps is probably increased by a
      variety of dietary and environmental factors. We found an association with
      current alcohol and cigarette consumption. The risk of polyps was increased three
      times in drinkers who did not smoke and two times in smokers who did not drink,
      with those who both drank and smoked having 12 times the risk of total
      abstainers. Since colonic adenomatous polyps are generally regarded as
      premalignant lesions, these results lend support to the view that alcohol
      consumption may be an important factor in the pathogenesis of colorectal
      neoplasia, thus reinforcing the proposed polyp/carcinoma sequence in colorectal
      carcinogenesis. The role of smoking, however, is less clear particularly since
      the lack of association of colorectal carcinoma and smoking has been reported in
      many other studies.

PMID- 1991641
TI  - How bad are the symptoms and bowel dysfunction of patients with the irritable
      bowel syndrome? A prospective, controlled study with emphasis on stool form.
AB  - Since it is not known whether the symptoms and bowel function of patients with
      the irritable bowel syndrome are truly abnormal we used diaries and frequent
      telephone interviews over a 31 day period to assess symptoms, defecation, and
      stool types in 26 unselected female hospital patients with the irritable bowel
      syndrome, 27 women who admitted to recurrent colonic pain but had not consulted a
      doctor (non-complainers), and 27 healthy control subjects. Unexpectedly,
      abdominal pain and bloating occurred in most of the control subjects. Pain,
      however, was six times more frequent in the patients and was more often
      considered severe. Bloating occurred three times more often. Defecation was more
      frequent, more erratic in timing and stool form, and more likely to produce
      stools of extreme forms, indicating rapid fluctuations in intestinal transit
      time. Urgency was four times more prevalent in patients than control subjects.
      Straining to finish defecating was nine times more prevalent and was often
      accompanied by feelings of incomplete evacuation--a combination which could lead
      to the misdiagnosis of constipation. The normal relation between stool form and
      the above symptoms was distorted, possibly due to rectal irritability. Non
      complainers were intermediate between patients and control subjects in almost
      every parameter but were closer to control subjects than to patients. Patients
      with the irritable bowel syndrome have real cause for complaint and their bowel
      function is truly abnormal.

PMID- 1991642
TI  - Coeliac disease and malignancy of the duodenum: diagnosis by endoscopy,
      successful treatment of the malignancy, and response to a gluten free diet.
AB  - A patient presented with subtotal villous atrophy and a malignant duodenal tumour
      of uncertain histogenesis. He was successfully treated by resection and
      chemotherapy and the small bowel mucosa recovered on a gluten free diet. The
      tumour was diagnosed at upper gastrointestinal endoscopy when barium studies and
      abdominal computed tomography were normal, thus making this one of the earliest
      coeliac malignancies diagnosed.

PMID- 1991643
TI  - Successful control of bleeding from gastric antral vascular ectasia (watermelon
      stomach) by laser photocoagulation.
AB  - We report a case of gastric antral vascular ectasia in a patient with primary
      biliary cirrhosis in whom chronic blood loss was a major problem. She required
      repeated blood transfusions that were complicated by reactions and still had
      persistent anaemia. She was treated with laser phototherapy in the form of
      quadrantic photocoagulation with a neodynium yttrium-aluminium-garnet laser. This
      greatly improved the endoscopic appearance of the gastric lesions and effectively
      controlled blood loss. She required no further transfusions. Bleeding recurred
      after 11 months which was controlled by further laser photocoagulation.

PMID- 1991644
TI  - Provision of gastrointestinal endoscopy and related services for a district
      general hospital. Working Party of the Clinical Services Committee of the British
      Society of Gastroenterology.
AB  - (1) The number of endoscopic examinations performed is rising. Epidemiological
      data and the workload of well developed units show that annual requirements per
      head of population are approaching: Upper gastrointestinal 1 in 100 Flexible
      sigmoidoscopy 1 in 500 Colonoscopy 1 in 500 ERCP 1 in 2000 (2) Open access
      endoscopy to general practitioners is desirable and increasingly sought. For a
      district general hospital serving a population of 250,000, this workload entails
      about 3500 procedures annually, performed during 10 half day routine sessions
      plus emergency work. (3) High standards of training and experience are needed by
      all staff, who must work in purpose built accommodation designed to promote
      efficient and safe practice. (4) The endoscopy unit should be adjacent to day
      care facilities and near the x ray department. There should be easy access to
      wards. (5) An endoscopy unit needs at least two endoscopy rooms; a fully
      ventilated cleaning/disinfection area; rooms for patient reception, preparation,
      and recovery; and accommodation for administration, storage, and staff amenities.
      (6) The service should be consultant based. At least 10 clinical sessions are
      required, made up of six or more consultant sessions and two to four clinical
      assistant, hospital practitioner, or staff specialist sessions. Each consultant
      should be expected to commit at least two sessions weekly to endoscopy. Extra
      consultant sessions may be needed to provide an efficient service. (7) A
      specially trained nursing sister (grade G or H) and five other endoscopy nurses
      are needed to care for the patients; their work may be supplemented by care
      assistants. (8) A new post of endoscopy department assistant (analogous to an
      operating department assistant) is proposed to maintain and prepare instruments,
      and to give technical assistance during procedures. (9) A full time secretary
      should be employed. Records, appointments, and audit should be computer based.
      (10) ERCP needs the collaboration of an interventional radiologist working with
      high quality x ray equipment in a specially prepared radiology screening room.
      This facility may need to serve more than one hospital. (11) A gastrointestinal
      measurement laboratory can conveniently be combined with the endoscopy unit. In
      some hospitals one or more gastrointestinal measurement technicians may staff
      this laboratory. (12) An endoscopy unit is a service department analogous to a
      radiology department. It needs an annual budget.

PMID- 1991645
TI  - Adenosine receptors and signaling in the kidney.
AB  - It is now generally accepted that adenosine is capable of regulating a wide range
      of physiological functions. Nowhere is the diversity of this action better
      illustrated than in the kidney. When adenosine binds to plasma membrane receptors
      on a variety of cell types in the kidney, it stimulates functional responses that
      span the entire spectrum of renal physiology, including alterations in
      hemodynamics, hormone and neurotransmitter release, and tubular reabsorption.
      These responses to adenosine appear to represent a means by which the organ and
      its constituent cell types can regulate their metabolic demand such that it is
      maintained at an appropriate level for the prevailing metabolic supply.
      Extracellular adenosine, produced from the hydrolysis of adenosine 5'
      monophosphate and stimulated by increased substrate availability and enzyme
      induction, acts on at least two types of cell surface receptors to stimulate or
      inhibit the production of cyclic adenosine-3',5'-monophosphate and also acts in
      some renal cells to stimulate the production of inositol phosphates and elevation
      of cytosolic calcium concentration. To understand when and why this complicated
      system becomes activated, how it interacts with other known extracellular
      effector systems, and ultimately how to manipulate the system to therapeutic
      advantage by selective agonists or antagonists, requires a detailed knowledge of
      renal adenosine receptors and their signaling mechanisms. The following
      discussion attempts to highlight our knowledge in this area, to present a
      modified hypothesis for adenosine as a feedback regulator of renal function, and
      to identify some important questions regarding the specific cellular mechanisms
      of adenosine in renal cell types.

PMID- 1991646
TI  - Angiotensins. A family that grows from within.

PMID- 1991647
TI  - Prevention of hypertension and vascular changes by captopril treatment.
AB  - Treatment of female spontaneously hypertensive rats (SHR) and control Wistar
      Kyoto (WKY) rats with captopril was carried out by the addition of the drug in
      the drinking water throughout pregnancy and lactation and after weaning. At 28
      weeks of age, average systolic blood pressure of treated SHR was 113 +/- 3 mm Hg,
      which was below that of control SHR (188 +/- 3 mm Hg) and WKY rats (124 +/- 3 mm
      Hg). Body weight and heart rate of the SHR were not affected by the treatment.
      Tissue level of catecholamines was increased by captopril treatment in the
      superior cervical ganglia but remained unchanged in the plasma, heart, mesenteric
      arteries, and the adrenal glands of both SHR and WKY rats. Left ventricular
      weight, wall thickness, and internal diameter of the left ventricle in the SHR
      were reduced by the treatment. Morphometric measurements of the mesenteric
      arteries showed that vascular alterations present in the control SHR were
      prevented by the treatment. In the superior mesenteric artery and large
      mesenteric artery, smaller lumen size at maximal relaxation found in the control
      SHR was normalized to the level of the WKY rats. Hypertrophy of the medial wall
      in the superior mesenteric, large and small mesenteric arteries, and an increase
      in the number of smooth muscle cell layers in the large mesenteric artery of the
      SHR were prevented by the treatment. Perfusion study of the mesenteric vascular
      bed showed that reactivity of these vessels to norepinephrine was reduced, and
      sensitivity to norepinephrine (as determined by the effective dose that causes
      50% of maximal response) was increased in the SHR by captopril treatment.
      Sensitivity of the tail artery in response to norepinephrine was not altered by
      the treatment. We conclude that long-term treatment with captopril of SHR before
      and after birth prevented the development of hypertension, structural and
      functional alterations of the mesenteric arteries, and cardiac hypertrophy.

PMID- 1991648
TI  - Isolation of preferentially expressed genes in the kidneys of hypertensive rats.
AB  - By differential hybridization, three complementary DNAs designated as S3, S2, and
      SA were isolated, and the corresponding messenger RNAs (mRNAs) were
      differentially expressed between the kidneys of spontaneously hypertensive rats
      (SHR) and normotensive Wistar-Kyoto (WKY) rats. S3 is identical to cytochrome
      P450 IV A2. SA encoded a protein of 546 amino acid residues, and its carboxyl
      terminal region had a slight homology to luciferase. No homologous sequence has
      been reported in S2 sequences. S3 mRNA was about four times more abundantly
      expressed in the kidneys of 28-day-old SHR than in those of age-matched WKY rats,
      but there was no difference at age 16 weeks. A low NaCl diet positively modulated
      the expression of the S3 gene. S2 mRNA was almost undetectable in the kidneys of
      28-day-old WKY rats but was clearly detected in those of age-matched SHR. The
      expression level of S2 mRNA in the livers of 16-week-old SHR was about five times
      higher than that of age-matched WKY rats. The expression of S2 mRNA in the livers
      was modulated by dietary NaCl and captopril. SA mRNA was more than 10 times more
      abundantly expressed in the kidneys of SHR than in those of WKY rats from age 4
      weeks. With the administration of captopril, the expressions of SA mRNA in the
      livers of SHR were positively modulated. Because these three genes are not only
      differentially expressed between SHR and WKY rats but also related to sodium
      metabolism or blood pressure control, the identification of these genes may
      provide important probes to examine the mechanisms of hypertension.

PMID- 1991649
TI  - Impaired insulin action on skeletal muscle metabolism in essential hypertension.
AB  - Previous studies have shown that essential hypertension is frequently associated
      with insulin resistance. The tissues responsible for this metabolic alteration
      have not been defined. We tested the hypothesis that skeletal muscle is the site
      of insulin resistance of essential hypertension with the use of the perfused
      forearm technique. Eight hypertensive (age 42 +/- 3 years, body mass index 27 +/-
      1 kg/m2, intra-arterial mean blood pressure 126 +/- 4 mm Hg) and seven
      normotensive (age 48 +/- 3 years, body mass index 26 +/- 1 kg/m2, mean blood
      pressure 95 +/- 4 mm Hg) male volunteers were studied. After glucose ingestion
      (40 g/m2), normal glucose tolerance in the patients was maintained at the expense
      of a heightened plasma insulin response, suggesting the presence of insulin
      resistance. During graded, local (intra-arterial) hyperinsulinemia encompassing
      the physiological range (12-120 milliunits/l), glucose uptake by forearm tissues
      was significantly (p less than 0.03) reduced in the hypertensive subjects as
      compared with the controls at each of five insulin steps, by 43% on the average.
      In addition, forearm lactate and pyruvate release were significantly less
      stimulated in the hypertensive than in the normotensive group (p less than 0.01
      for both), presumably as a consequence of the decreased glucose influx. Forearm
      exchange of oxygen, carbon dioxide, lipid substrates (free fatty acids, glycerol,
      and beta-hydroxybutyrate), and potassium were similar in the hypertensive and
      normotensive groups in the basal state. Insulin had no effect on oxygen
      consumption, carbon dioxide production, and respiratory quotient in either study
      group, whereas it stimulated free fatty acids, glycerol, and potassium uptake to
      the same extent in the hypertensive and normotensive groups.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1991650
TI  - Nicotine impairs reflex renal nerve and respiratory activity in
      deoxycorticosterone acetate-salt rats.
AB  - Smoking exacerbates the increase in arterial pressure in hypertension. The effect
      of nicotine on the baroreceptor-mediated reflex responses of renal nerve activity
      (RNA), heart rate, and respiratory activity (minute diaphragmatic activity [MDA])
      after bolus injections of phenylephrine was compared in deoxycorticosterone
      acetate (DOCA)-salt sensitive and normotensive rats. Osmotic minipumps that
      dispensed either nicotine (2.4 mg/kg/day) or saline were implanted in DOCA and
      normotensive rats for 18 days. Anesthetized DOCA-nicotine, DOCA-saline, control
      nicotine, and control-saline rats had mean arterial pressures (MAP) of 117 +/- 3,
      110 +/- 9, 90 +/- 3, and 89 +/- 5 mm Hg, respectively. Nicotine decreased the
      sensitivity (p less than 0.05) of baroreceptor reflex control of RNA (% delta
      RNA/delta MAP) in the DOCA-nicotine rats (-0.92 +/- 0.08) compared with the DOCA
      saline (-1.44 +/- 0.16), control-nicotine (-1.45 +/- 0.08), or control-saline (
      1.45 +/- 0.21) rats. The reflex decrease in respiratory activity (% delta
      MDA/delta MAP x 100) was impaired (p less than 0.01) in both control-nicotine (
      24.5 +/- 3.3) and DOCA-nicotine (-18.2 +/- 4.6) rats compared with control-saline
      (-59.2 +/- 9.1) and DOCA-saline (-52.5 +/- 9.9) rats. The reflex decrease in
      heart rate (absolute delta HR/delta MAP) in both DOCA-nicotine (1.56 +/- 0.17)
      and control-nicotine (1.54 +/- 0.24) rats was augmented compared with DOCA-saline
      and control-saline rats (0.91 +/- 0.12 and 0.97 +/- 0.14).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1991651
TI  - Shear stress-induced release of nitric oxide from endothelial cells grown on
      beads.
AB  - An in vitro bioassay system was developed to study endothelium-mediated, shear
      stress-induced, or flow-dependent generation of endothelium-derived relaxing
      factor (EDRF). Monolayers of aortic endothelial cells were grown on a rigid and
      large surface area of microcarrier beads and were packed in a small column
      perfused with Krebs bicarbonate solution. The perfusate was allowed to superfuse
      three endothelium-denuded target pulmonary arterial strips arranged in a cascade.
      Fluid shear stress caused a flow-dependent release of EDRF from the endothelial
      cells. The action of EDRF was abolished by oxyhemoglobin and methylene blue, and
      the generation of EDRF in response to shear stress was markedly inhibited or
      abolished by NG-nitro-L-arginine, by NG-amino-L-arginine, by calcium-free
      extracellular medium, and by depleting endothelial cells of endogenous L
      arginine. Addition of L-arginine to arginine-deficient but not arginine
      containing endothelial cells rapidly restored the capacity of shear stress and
      bradykinin to generate EDRF. These observations indicate that fluid shear stress
      causes the generation of EDRF with properties of nitric oxide from aortic
      endothelial cells and that the bioassay system described may be useful for
      studying the mechanism of mechanochemical coupling that leads to nitric oxide
      generation.

PMID- 1991652
TI  - Nephrotoxicity of allopurinol is enhanced in experimental hypertension.
AB  - Hyperuricemia is present in 20-40% of pediatric and adult patients with essential
      hypertension. This metabolic abnormality may represent an additional risk factor
      for the development of cardiovascular disease. Therefore, we performed the
      following studies to determine 1) whether hyperuricemia is more prevalent in the
      spontaneously hypertensive rat (SHR) and 2) whether allopurinol treatment has a
      beneficial effect on the development of hypertension in this strain, based on its
      capacity to lower the serum uric acid concentration and to act as an antioxidant
      agent. SHR and control Wistar-Kyoto (WKY) rats were assigned to two groups, one
      given tap water to drink and the other provided water containing allopurinol (400
      mg/l) to furnish an approximate daily dose equal to 100 mg/kg body wt. This
      treatment was maintained for 15 weeks. The serum uric acid levels were similar in
      untreated SHR and WKY rats (1.85 +/- 0.10 versus 1.66 +/- 0.14 mg/dl; p = 0.28).
      In the control WKY rat strain, allopurinol therapy did not adversely affect
      weight gain or hematocrit and did not cause an increase in mortality. It resulted
      in a moderate decrement in kidney function (creatinine clearance: allopurinol
      treated group 0.32 +/- 0.09 versus control group 0.46 +/- 0.04 ml/min/100 g body
      wt, in conjunction with mild-to-moderate tubulointerstitial inflammation
      (allopurinol-treated group 0.9 +/- 0.4 versus control group 0).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1991653
TI  - Effects of lovastatin treatment on red blood cell and platelet cation transport.
AB  - Hypercholesterolemia frequently accompanies hypertension, and it has been
      suggested that by affecting membrane lipid composition, hypercholesterolemia may
      cause or accentuate abnormalities in several red blood cell transports associated
      with hypertension. Such an effect might obfuscate the relation of membrane
      markers to hypertension and decrease their usefulness in genetic studies of the
      heritable basis of hypertension. To determine if changing plasma lipids affects
      membrane transport, we studied the effects of the cholesterol-lowering agent
      lovastatin on red blood cell lithium-sodium countertransport and sodium-potassium
      chloride cotransport, red blood cell sodium and water content, and platelet
      amiloride-sensitive volume responsiveness to cytoplasmic acidification, an
      indirect measure of sodium-proton exchange that has been proposed as a new
      membrane marker for hypertension. In a 24-week, placebo-controlled, double
      blinded, randomized trial, lovastatin significantly lowered total and low density
      lipoprotein cholesterol and raised high density lipoprotein cholesterol. Red
      blood cell lithium-sodium countertransport and sodium-potassium-chloride
      cotransport were not significantly altered. Red blood cell sodium content
      decreased significantly in the lovastatin-treated group, probably as a result of
      an increase in red blood cell sodium-potassium pump activity. Platelet amiloride
      sensitive responses to cytoplasmic acidification were significantly depressed by
      lovastatin treatment, suggesting that lowering plasma cholesterol may suppress
      platelet sodium-proton exchange. It has been hypothesized that the
      hyperlipidemias frequently observed in essential hypertensive patients may alter
      membrane lipid composition and affect membrane cation transport
      activities.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1991654
TI  - Maternal prenatal dietary potassium, calcium, magnesium, and infant blood
      pressure.
AB  - We studied the association between the prenatal diets of 212 mothers assessed by
      a semiquantitative food frequency questionnaire and the blood pressure of their
      infants. Prenatal potassium, calcium, and magnesium intakes were measured and
      adjusted for total caloric intake. Infant blood pressure was measured at 2-3 days
      and at 1, 6, and 12 months of age by using an ultrasonic-auscultatory device and
      was adjusted for cuff size, observer, and sleep/activity status, age in days in
      neonates, and weight at 6 and 12 months. Maternal prenatal potassium intake was
      inversely related to diastolic pressure at 6 months (r = -0.28, p less than 0.01)
      and at 12 months (r = -0.30, p less than 0.05). After adjustment for neonatal
      breast versus formula feeding, maternal prenatal calcium intake was inversely
      related to systolic blood pressure at 1 month (r = -0.21, p less than 0.01), and
      to diastolic blood pressure at 6 months (r = -0.27, p less than 0.01) and 12
      months (r = -0.24, p less than 0.05). Maternal prenatal magnesium intake was
      inversely related to 6-month systolic blood pressure (r = -0.20, p less than
      0.05). In multivariable models with all three cations, maternal prenatal
      potassium intake was independently and inversely related to diastolic blood
      pressure at 6 and 12 months. Maternal prenatal calcium intake was independently
      related to 1-month systolic and 6-month diastolic blood pressure. Age-specific
      infant blood pressure differences between the upper and lower quartiles of
      maternal prenatal cation intakes ranged from 3 to 7 mm Hg.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1991655
TI  - Characterization of auscultatory gaps with wideband external pulse recording.
AB  - Three types of auscultatory gaps, called G1, G2, and G3, that occur during blood
      pressure measurement have been identified by using wideband external pulse
      recording. We have previously shown that the wideband external pulse recorded
      during cuff deflation can be separated into three components (K1, K2, and K3),
      one of which (K2) is closely related to the Korotkoff sound. G1 occurs with cuff
      pressure just below systolic and is characterized by the presence of K1 and K2
      with intermittent disappearance of K2. G1 gaps are related to a phasic decrease
      of arterial (systolic) pressure and were exhibited by 13 of 60 hypertensive
      patients. G2 gaps are related to a phasic increase of arterial (diastolic)
      pressure, occur when cuff pressure is just above diastolic, and are characterized
      by the presence of K1, K2, and K3 with intermittent disappearance of K2. Seven of
      60 hypertensive patients exhibited a G2 gap. G3 gaps occur with cuff pressure
      between systolic and diastolic and are characterized by an underdeveloped or
      blunted K2 signal. Three of 60 hypertensive patients exhibited a G3 gap. The
      identification of auscultatory gaps in relation to the wideband external pulse
      provides a qualitative measure of their existence, can be of significant value in
      better understanding aspects of the auscultatory blood pressure measurement
      technique, and provides an objective basis with which to better understand the
      mechanisms that cause them.

PMID- 1991656
TI  - Sir Horace Smirk. Pioneer in drug treatment of hypertension.
AB  - Sir Horace Smirk deserves much of the credit for establishing the benefits of
      reducing blood pressure. He was one of the main early proponents of the idea that
      it was the raised intra-arterial pressure itself that caused many of the cardiac
      and vascular complications of hypertension. His training in both pharmacology and
      internal medicine enabled him to devise practical methods for successful
      treatment of hypertension with ganglion blocking drugs such as hexamethonium. The
      major clinical benefits that followed such drug treatment proved a great stimulus
      to the development of drugs with fewer disadvantages and to widespread acceptance
      of the beneficial effects of antihypertensive drug treatment.

PMID- 1991657
TI  - [Mastication efficiency in denture wearers].

PMID- 1991658
TI  - Cardiomyopathy: a necessary revision of the WHO classification.
AB  - The classification of myocardial disease proposed by the WHO/ISFC task force in
      1980 distinguishes specific heart muscle diseases from myocardial diseases of
      unknown origin, termed cardiomyopathies, and differentiated into the dilated,
      hypertrophic and restrictive forms. This last group includes
      endomyocardiofibrosis and fibroblastic parietal endocarditis. In more recent
      years, two new forms of heart muscle disease have been recognized: so-called
      "primary" restrictive cardiomyopathy and arrhythmogenic right ventricular
      cardiomyopathy. Primary restrictive cardiomyopathy is characterized anatomically
      by normally sized, non-hypertrophic ventricles with dilated atria, and
      functionally by impaired diastolic compliance due to myocardial stiffness. The
      clinical picture is that of chronic congestive heart failure; histology shows
      interstitial fibrosis and myocardial disarray, but not hypereosinophilia. In
      arrhythmogenic right ventricular cardiomyopathy, the myocardium of the right
      ventricular free wall is substituted by fibrous and/or adipose tissue, which
      results in regional dynamic alterations and ominous ventricular arrhythmias. The
      left ventricle is usually spared. Both forms should be classified as heart muscle
      diseases of unknown origin, and kept clearly distinct from the other
      cardiomyopathies listed in the WHO classification.

PMID- 1991659
TI  - Scanning electron microscope features of rheumatic vegetations in acute rheumatic
      carditis.
AB  - We have studied four cases of acute rheumatic carditis at autopsy in which the
      cardiac valves revealed rheumatic vegetations. The features of these vegetations
      were investigated by scanning electron microscopy. There was a loss of the normal
      mosaic arrangement of endothelial cells and marked architectural modifications of
      the valvar collagen. These features explain well the pathologic processes of
      rheumatic valvitis and the infective complications, if any, thereof. To the best
      of our knowledge, this is the first time that an analysis has been made of the
      structure of the surface of rheumatic vegetations.

PMID- 1991660
TI  - Detection of myosin gene expression in the developing heart using probes derived
      by polymerase chain reaction.
AB  - The polymerase chain reaction provides a rapid method for the molecular cloning
      of DNA probes suitable for the detection of specific messenger RNA. We have used
      this approach to prepare probes specific for human cardiac myosin messenger RNA
      and demonstrate here the use of such probes in the analysis of human cardiac
      development by hybridization in situ to sections of fetal tissue. This
      combination of techniques is suitable for the detection of any messenger RNA for
      which sequence data are available, and offers a powerful new approach to the
      analysis of cardiac development.

PMID- 1991661
TI  - A case of double inlet left ventricle in a 59-year-old man.
AB  - An autopsy case of a 59-year-old man with double inlet left ventricle with a
      rudimentary right ventricle and discordant ventriculo-arterial connexion is
      reported. No surgery was performed during his life time and all clinical and
      echocardiographical findings had led to the diagnosis of a ventricular septal
      defect. The correct diagnosis could only be made after autopsy.

PMID- 1991662
TI  - Acquired aorto-coronary vein fistula after bypass graft surgery: report of two
      cases with long-term follow-up.
AB  - Two patients who underwent bypass surgery with saphenous grafts had a fistula
      resulting from inadvertent grafting of the cardiac vein correspondent to a
      targeted diagonal artery. Hemodynamic effects at rest were restricted to moderate
      elevation of the pulmonary blood flow, by 23 and 13% respectively, at 5 and 12
      months postoperatively. No objective signs of ischemia could be elicited in
      either patient, in the fistula related region, and left ventricular function
      remained within normal limits in both cases throughout the follow-up period (36
      and 24 months, respectively).

PMID- 1991663
TI  - Ultrastructure of naturally occurring subcutaneous nodule in acute rheumatic
      fever.
AB  - Electron microscopic evaluation of subcutaneous nodules excised from two cases of
      acute rheumatic fever showed an electron dense and smudgy material which had a
      distinct filamentous appearance in places. The latter was recognized as collagen.
      This corresponded to the fibrinoid necrosis seen under the light microscope. In
      addition, several histiomonocytic cells and fibroblasts were seen. A large number
      of cells were degenerated. A fair degree of resemblance of the nodule both by
      light and electron microscopy to the rheumatoid nodule was noted.

PMID- 1991664
TI  - The effects of positive and negative extrathoracic pressure ventilation on
      pulmonary blood flow after the total cavopulmonary shunt procedure.
AB  - Pulmonary blood flow patterns were studied during the application of varying
      extrathoracic pressure in 2 patients after total cavopulmonary anastomosis. The
      application of negative extrathoracic pressure was associated with large
      increases in pulmonary blood flow, while positive extrathoracic pressure, caused
      retrograde flow away from the lungs. These preliminary observations suggest that
      negative extrathoracic pressure may be useful as a means of respiratory support
      in patients after right heart bypass procedures.

PMID- 1991665
TI  - "Anatomically corrected malposition": a rare case with bilateral absence of a
      complete subarterial muscular infundibulum.
AB  - A unique case of anatomically corrected malposition of great arteries with a
      bilateral absence of a complete subarterial muscular infundibulum is presented.
      The other unusual feature of the case was absence of any complex associations and
      interestingly an intact ventricular septum. The presenting lesion was valvar
      pulmonary stenosis and balloon valvotomy could not be achieved because of
      abnormal relationship of the great vessels.

PMID- 1991666
TI  - Long-term follow-up of coarctation of the aorta repaired by patch angioplasty.
AB  - The long-term complications of patch plasty repair for coarctation of the aorta
      were assessed retrospectively in 119 patients who were operated upon from 4 days
      to 13 years of age. There were 7 late deaths and 17 patients were lost to follow
      up. Thus 95 patients were followed up for a minimum period of 3 years (mean 6.3
      years). In addition, graded exercise tests were performed on 15 patients and 11
      normal controls, measuring systolic blood pressure response and arm-leg blood
      pressure gradients. In this series, 16 patients (17%) were hypertensive, while 25
      (26%) had a resting systolic arm-leg gradient greater than 20 mm Hg. Re
      coarctation occurred more frequently when surgery had been undertaken under 1
      month of age. Review of chest X-rays revealed calcification in the patch in 4
      patients, one of whom subsequently went on to aneurysm formation. In a second
      child aneurysm formation was detected at repeat operation. Exercise tests showed
      a significantly higher systolic arm pressure in patients (mean: 165.3 mm Hg) when
      compared to controls (mean: 139.2 mm Hg) (P = 0.017) and a significant increase
      in arm-leg systolic gradient viz. 36 and 5.9 mm Hg, respectively (P = 0.0016). A
      good correlation was found between the systolic arm pressure and the systolic arm
      leg gradient after exercise (r = 0.822; P = 0.0001). We conclude that the most
      important long-term complication following an aortic patch plasty, is re
      stenosis. The development of an aneurysm was observed only twice. We believe that
      this apparently rare occurrence, as assessed on chest radiographs; is related to
      the young age (53% under 1 year) at which the repairs were carried out. Another
      possible reason may be that the follow-up period is not yet long enough.

PMID- 1991667
TI  - Balloon atrial septostomy under two-dimensional echocardiographic control.
AB  - We report our experience with balloon atrial septostomy under two-dimensional
      echocardiographic guidance only in 44 newborn patients (39 patients with
      transposition of the great arteries) who needed creation of an interatrial
      communication. Using standard echocardiographic projections septostomy with
      creation of large atrial septal defects was easy in 41 newborns. In 3 patients
      insertion of a large Eustachian valve at the interatrial septum prevented
      adequate pull-throughs with larger balloon sizes. No serious complications due to
      the procedure were noted. Balloon atrial septostomy under two-dimensional
      echocardiographic control is a quick, effective and safe method which can be
      performed on the intensive care unit.

PMID- 1991668
TI  - Echocardiography as a tool for determining the incidence of congenital heart
      disease in newborn babies: a pilot study in Hong Kong.
AB  - We studied, with echocardiography as the main tool, the incidence of congenital
      heart disease in newborn babies in Hong Kong. The population examined was the
      20,928 babies who were born alive in the Prince of Wales Hospital from January
      1987 to December 1989. All had a thorough physical examination by a paediatrician
      after birth, and an estimated 95% of the babies who were discharged from hospital
      received another routine physical examination at one of the five local Maternal
      and Child Health Centres within two months of birth. All babies with either
      suspected congenital heart disease or multiple congenital abnormalities were
      referred to the paediatric cardiologists in the Prince of Wales Hospital for
      further cardiovascular assessment that included echocardiographic examination. In
      all, 492 babies had Doppler and cross-sectional echocardiographic studies.
      Various abnormalities of the cardiovascular system were diagnosed in 216 babies.
      Almost all the babies who died within two months of life underwent autopsy. This
      proved the presence of congenital cardiac malformations in 15 babies, of whom 10
      had correct echocardiographic diagnoses during life. One had a patent arterial
      duct which was missed by the echocardiography. The other four babies did not have
      echocardiographic examination while alive, either because of early death or
      absence of clinical suspicion. In total, congenital cardiac malformations were
      confirmed in 221 babies by echocardiographic examination and autopsy. Excluding
      82 premature babies with patency of the arterial duct, and 6 babies with
      transient tricuspid regurgitation, there were 133 cases of structural cardiac
      malformation in the studied population, giving an incidence of 6.35 per thousand
      live births.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1991669
TI  - Transcardiac alteration of neutrophil function before and after coronary
      thrombolysis in human myocardial infarction.
AB  - We examined function of isolated neutrophils taken from aorta and coronary sinus
      before and after thrombolytic reperfusion in 17 patients whose infarct-related
      coronary arteries were totally occluded. Before reperfusion in left coronary
      artery disease, free radical generation by activated neutrophils in coronary
      sinus, assessed by ferricytochrome c reduction (phorbol myristate acetate, 10
      ng/ml) and luminol-enhanced chemiluminescence (A23187, 2 microM), was reduced by
      20% (P less than 0.05) and 30% (P less than 0.05), respectively, compared with
      those in aorta. Neutrophil aggregation (A23187, 10 microM) and chemotactic
      activity (formyl-methionyl-leucyl-phenylalanine, 5 microM) were also reduced in
      coronary sinus by 21% and 20%. After reperfusion the extent of such neutrophil
      function in coronary sinus recovered and was similar to that in aorta. There were
      no significant differences between neutrophil counts in aorta and coronary sinus
      before and after reperfusion. In right coronary artery disease, no significant
      changes were seen in these functions of neutrophils of aorta and coronary sinus
      before and after reperfusion. These results indicate that function of neutrophils
      passing through coronary circulation fluctuated significantly in association with
      reperfusion, suggesting (1) factor(s) that depress neutrophil function are
      produced in coronary circulation during myocardial ischemia and their effects are
      overcome after reperfusion or (2) activated neutrophils, trapped in the ischemic
      coronary bed, are washed out to coronary sinus after reperfusion.

PMID- 1991670
TI  - Morbidity following coronary artery revascularisation with the internal mammary
      artery.
AB  - To investigate the morbidity after coronary artery bypass grafting, one hundred
      and seventy-eight patients were retrospectively studied with a minimum follow-up
      period of one year. Although there was no difference in the incidence and
      distribution of pain in hospital, seventy percent of patients who had an internal
      mammary artery used as one of the bypass conduits experienced chest wound pain
      after discharge from hospital compared to 51.7% of patients who had vein grafts
      alone (P less than 0.05). Twenty-three percent of patients who had left internal
      mammary arteries harvested experienced chronic left-sided chest wall pain
      compared to 4.5% of patients who had vein grafts only (P less than 0.005). The
      possible factors responsible are discussed and a review made of the complications
      which may result from using the internal mammary artery in coronary artery
      surgery.

PMID- 1991671
TI  - The effects of the strain of returning to work on the risk of cardiac death after
      a first myocardial infarction before the age of 45.
AB  - Seventy-nine men who had suffered a myocardial infarction before the age of 45
      while they were vocationally active in the greater Stockholm area were followed
      for five years. Forty-nine survived without cardiac complications and 13 died due
      to ischaemic heart disease during the period of follow-up. These two contrasting
      groups were compared with regard to psychosocial risk factors at work before the
      first myocardial infarction (as reported by the patient when he was interviewed
      during the weeks after the onset of disease). It was hypothesized that returning
      to stressful work (high demands and limited possibilities of influencing
      decisions and developing skills) would be associated with an increased risk of
      death. All the subjects who died had returned to the work that they had performed
      prior to the first myocardial infarct. Work performed by these patients was
      described as having significantly higher psychological demands in relation to the
      possibility of learning new things and higher demands in relation to variety as
      well as almost significantly higher demands in relation to influence.
      Multivariate logistic regression with these factors concerning employment,
      together with biomedical risk factors recorded at the same time, showed that
      increasing age, increasing degree of coronary atherosclerosis and number of
      stenosed coronary arteries, as well as high demands in relation to the
      possibility of learning new things, were independent predictors of death due to
      coronary arterial disease. The remaining 17 subjects either survived a re
      infarction, or had coronary arterial by-pass surgery during the period of follow
      up. This heterogeneous group occupied intermediate positions with regard to
      psychosocial job factors.

PMID- 1991672
TI  - Correlation of cross-linked fibrin degradation products (D-dimer) with coronary
      angiographic lesion morphology.
AB  - We tested the hypothesis that complex irregular coronary lesions are "active"
      lesions and thus associated with ongoing fibrinolysis by measuring the
      degradation products of cross-linked fibrin (D-dimer) in 136 patients undergoing
      coronary arteriography. Blood samples obtained before catheterization were
      assayed by an enzyme linked immunosorbent assay (ELISA) using specific monoclonal
      antibodies for D-dimer particles. In the four groups with complex coronary
      morphologies (filling defects, extrinsic lesions with irregular borders and total
      occlusions with or without staining) the majority of patients (64%) had normal D
      dimer levels. The incidence of abnormal D-dimer levels was not significantly
      higher in any of these four groups than in the two groups with normal coronaries
      or with smooth lesions. In the same patients, however, the clinical diagnosis was
      predictive of the presence of elevated D-dimer levels. These findings suggest
      that complex coronary lesions are often not associated with ongoing fibrinolysis
      and that endogenous fibrinolysis frequently ceases in the presence of persistent
      clot.

PMID- 1991673
TI  - Acute and chronic efficacy of felodipine in congestive heart failure.
AB  - In 13 patients with congestive heart failure we tested the acute hemodynamic
      effects of 5 vs. 10 mg felodipine tablets, in a double-blind, cross-over study.
      One hour after felodipine 5 mg, echocardiographic ejection fraction (%), cardiac
      index (thermodilution-ml/min/m2), and pulmonary wedge pressure (mm Hg)
      significantly changed (from 21 +/- 2 to 26 +/- 2, 2350 +/- 150 to 2790 +/- 160,
      24 +/- 4 to 17 +/- 4) while they remained steady after felodipine 10 mg. The
      greatest stroke index increases were associated with felodipine 5 mg in 12
      patients and 10 mg in 1 patient. Therefore we evaluated (open study) the long
      term (2 months- 1 year) clinical and hemodynamic efficacy following the treatment
      with the acutely most effective dose (twice daily). After 2 months ejection
      fraction, cardiac index and pulmonary wedge pressure were respectively 24 +/- 2,
      2550 +/- 150, and 18 +/- 4 (12 hours after the last drug administration, n = 11,
      P less than 0.02 from baseline). These parameters further increased one to two
      hours after the following administration of felodipine. Clinical improvement
      (reduction of 1 functional class, according to the New York Heart Association)
      was observed in 8/13 patients. These 8 patients participated to the one year
      follow-up. In 5 patients follow-up was interrupted because of acute
      cardiovascular events. However, before study interruption (5 patients) or ending
      (3 patients) clinical status did not worsen and ejection fraction remained higher
      than in the pretreatment period. Therefore, low dose felodipine might be used in
      the treatment of congestive heart failure.

PMID- 1991674
TI  - Pathogenesis of hypertrophic cardiomyopathy: another viewpoint.
AB  - A genetically determined error in the handling of catecholamines by the
      developing heart has been speculated to cause hypertrophic cardiomyopathy. A
      critical appraisal of the published literature reveals that there is little
      actual experimental or clinical evidence favouring the role of catecholamines in
      the pathogenesis of hypertrophic cardiomyopathy. Other factors seem to be more
      important. An abnormality of myocardial growth, either induced by excessive
      growth promoting substance, or a genetically determined abnormality in myocardial
      responses to normal growth factors during life (but not in the fetal handling of
      catecholamines) is likely to be responsible for hypertrophic cardiomyopathy.

PMID- 1991675
TI  - The secondary data bases of health services research: need for a national
      inventory.

PMID- 1991676
TI  - Teaching hospital costs: the effects of medical staff characteristics.
AB  - This article examines the effect of medical staff behavior on the cost of
      hospital-based care and graduate medical education, and shows its implications
      for estimation of hospital costs. The empirical work brings a unique new data
      source for these characteristics to the estimation process. Our results indicate
      that there are important economies of scale and scope in hospital production,
      both for inpatient stays and for residency training. Controlling for medical
      staff characteristics significantly reduces the estimated costs of residency
      training. Staff characteristics may be capturing aspects of the quality of
      inpatient care and residency training provided by the hospital.

PMID- 1991677
TI  - Hospitals as interpretation systems.
AB  - In this study of 162 hospitals, it was found that the chief executive officer's
      (CEO's) interpretation of strategic issues is related to the existing hospital
      strategy and the hospital's information processing structure. Strategy was
      related to interpretation in terms of the extent to which a given strategic issue
      was perceived as controllable or uncontrollable. Structure was related to the
      extent to which an issue was defined as positive or negative, was labeled as
      controllable or uncontrollable, and was perceived as leading to a gain or a loss.
      Together, strategy and structure accounted for a significant part of the variance
      in CEO interpretations of strategic events. The theoretical and managerial
      implications of these findings are discussed.

PMID- 1991678
TI  - Adult day health care evaluation study: methodology and implementation. Adult Day
      Health Care Evaluation Development Group.
AB  - The Adult Day Health Care Evaluation Study was developed in response to a
      congressional mandate to study the medical efficacy and cost effectiveness of the
      Adult Day Health Care (ADHC) effort in the Department of Veterans Affairs (VA).
      Four sites providing ADHC in VA facilities are participating in an ongoing
      randomized controlled trial. Three years of developmental work prior to the study
      addressed methodological issues that were problematic in previous studies. This
      developmental work resulted in the methodological approaches described here: (1)
      a patient recruitment process that actively recruits and screens all potential
      candidates using empirically developed admission criteria based on predictors of
      nursing home placement in VA; (2) the selection and development of measures of
      medical efficacy that assess a wide range of patient and caregiver outcomes with
      sufficient sensitivity to detect small but clinically important changes; and (3)
      methods for detailed, accurate, and efficient measurement of utilization and
      costs of health care within and outside VA. These approaches may be helpful to
      other researchers and may advance the methodological sophistication of long-term
      care program evaluation.

PMID- 1991679
TI  - In vitro radiation survival parameters of human colon tumor cells.
AB  - As part of an ongoing research program in the biology of human colon cancer
      cells, a database is being generated on the radiation responses of established
      lines in vitro. In this report, data are summarized on the graded single dose
      clonogenic survival responses to graded single doses of 250 kVp X rays of 16
      exponentially growing lines. These data were analyzed using the linear quadratic
      (LQ) formalism for X ray inactivation; the 95% confidence limits on the colony
      forming efficiencies (CFEs), the alpha and beta parameters from the LQ equation,
      the surviving percentage at 2 Gy, and the mean inactivation dose (D, Gy) are
      listed herein. The average D from these 16 colon tumor lines was 2.35 Gy (95%
      confidence limits 2.10-2.60 Gy), which indicates that these tumor cells are of
      equal radioresistance to melanoma or head and neck cells, with only glioblastoma
      cells being of greater radioresistance.

PMID- 1991680
TI  - 5-Fluorouracil modulation of radiosensitivity in cultured human carcinoma cells.
AB  - We evaluated conventional pulse exposure versus continuous exposure models of 5
      fluorouracil (5-FU) radiosensitization in HT-29 (human colon adenocarcinoma) and
      DU-145 (human prostate cancer adenocarcinoma) cell lines. Cell survival following
      treatment with drug and/or radiation was determined by colony formation assays.
      Radiation was delivered either by itself, approximately midway through a 1-hr
      exposure to 5-FU (10 micrograms/ml), or at various times following initiation of
      exposure to 5-FU (0.5 microgram/ml) present throughout the entire period of
      incubation. Drug concentrations were selected to approximate those achieved in
      vivo in humans. HT-29 cells showed a plating efficiency of 87% and similar
      cytotoxicity (survival reduced to 0.57-0.71) for all 5-FU conditions. The Do's of
      the radiation survival curves were not different for 1 hr of 5-FU exposure versus
      radiation alone. However, continuous exposure conditions demonstrated
      statistically significantly different Do's from radiation alone and pulse 5-FU
      exposure. DU-145 cells displayed a plating efficiency of 17% and cytotoxicities
      of 0.10-0.91 for the 5-FU conditions. DU-145 cells showed different radiation 5
      FU interactions: 5-FU produced statistically significant changes in Do well as
      the differences between cell lines insofar as their radiosensitization by 5-FU
      underscore the caution required in extrapolating these radiobiologic models to
      the clinical setting.

PMID- 1991681
TI  - Radiation induction of drug resistance in RIF-1: correlation of tumor and cell
      culture results.
AB  - The RIF-1 tumor line contains cells that are resistant to various anti-neoplastic
      drugs, including 5-fluorouracil (5FU), methotrexate (MTX), adriamycin (ADR), and
      etoposide (VP16). The frequency of these drug-resistant cells is increased after
      irradiation. The frequency of drug-resistant cells and the magnitude of radiation
      induced drug resistance are different in cell culture than in tumors. The dose
      response and expression time relationships for radiation induction of drug
      resistance observed in RIF-1 tumors are unusual. We hypothesize that at high
      radiation doses in vivo, we are selecting for cells that are both drug resistant
      and radiation resistant due to microenvironmental factors, whereas at low
      radiation doses in vivo and all radiation doses in vitro, we are observing true
      mutants. These studies indicate that there can be significant differences in drug
      resistance frequencies between tumors and their cell lines of origin, and that
      radiation induction of drug resistance depends significantly on whether the
      induction is done in tumors or in cell culture. These results imply that theories
      about the induction of drug resistance that are based on cell culture studies may
      be inapplicable to the induction of drug resistance in tumors.

PMID- 1991682
TI  - Interaction of platinum drugs with clinically relevant x-ray doses in mammalian
      cells: a comparison of cisplatin, carboplatin, iproplatin, and tetraplatin.
AB  - Whereas the interaction between radiation and platinum complexes has never been
      pronounced in radiobiological experiments (to 30 Gy in mammalian cells), there
      have been reports of interest in this combination in the clinic, where
      fractionated doses of approximately 2 Gy are used. Our studies on the marked
      interaction in hypoxia at the 80% survival level (1-2.5 Gy) with cisplatin have
      been extended to second generation platinum drugs of clinical interest. The
      studies in the lower radiation dose region have been facilitated by the use of
      the cell analyzer DMIPS to identify individual cells and follow them
      microscopically to assess for clonogenic ability. Chinese hamster V79 cells were
      used, which were exposed to drug for 1 hr prior to irradiation in hypoxia (or
      air). None of the drugs give an enhancement ratio (ER) greater than 1.3 in the
      high radiation dose region, whereas all can produce ER80% (ER calculated at iso
      survival of 80%) of 2 or higher at low doses in hypoxic cells. The enhancement of
      radiation kill in oxic V79 cells (ER's to 1.1 at 1-2% S) disappears at low doses
      (ER80% = 1.0) except for tetraplatin, where a moderate ER80% (to 1.64) was
      measured. Comparison of the hypoxic interaction on a concentration basis suggests
      that cisplatin is the best drug at low x-ray doses and low concentrations, but
      the interaction reaches a plateau at ER80% approximately 2.0. Tetraplatin
      continues to give better interaction with increasing concentration (up to ER80% =
      3.7 at 25 microM). Interaction of radiation with the less toxic drugs, iproplatin
      and carboplatin, used at around 100 microM can be improved by longer exposure
      times prior to irradiation. Comparison on the basis of toxicity, for which the
      plating efficiency was used, suggests that cisplatin gives a better interaction
      than the three newer drugs for a given level of toxicity in hypoxic V79 cells.

PMID- 1991683
TI  - Schedule-dependent therapeutic gain from the combination of fractionated
      irradiation plus c-DDP and 5-FU or plus c-DDP and cyclophosphamide in C3H/Km
      mouse model systems.
AB  - Cytotoxic drugs were administered either in single or fractionated doses before,
      during, or after a standard course of 5 daily X ray exposures. SCCVII and RIF-1
      tumors were grown from cells implanted in the gastrocnemius muscles of syngeneic
      C3H/Km mice, and treatments were evaluated by regrowth delay (GD). Non-tumor
      bearing mice were irradiated locally to the upper abdomen for analysis of
      intestinal crypt cell survival, an acute normal tissue effect; other non-tumor
      bearing mice were irradiated locally to the thorax for analysis of early
      (pneumonitis) and late (fibrosis) effects on the lungs, as reflected in changes
      in breathing rates. In a series of experiments to test the combination of i.p. 5
      FU, cis-DDP, and X ray, dose effect factors (DEF's) were compared so that
      therapeutic gain factors (TGF's) could be calculated from the ratio, DEF
      (tumor)/DEF (normal tissue). The highest TGF, 6.7 (tumor/duodenum), was obtained
      for the schedule in which 100 mg/kg 5-FU was given 24 hr before the simultaneous
      administration of 1.6 mg/kg cis-DDP and X ray for 5 consecutive days. The
      following summary refers only to tumor growth delay data. In confirmation of
      previous extensive experiments, the combination of cis-DDP + X ray showed supra
      additivity, whether the drug was given in a single dose (abbreviated P) or
      simultaneously with X ray (abbreviated px), that is, P x x x x x or px px px px
      px. For CY + X ray, the greatest supra-additivity was obtained for either C x x x
      x x or x x x x x C. 5-FU alone did not act supra-additively with fractionated
      irradiation, but the addition of 5-FU to cis-DDP + X ray was supra-additive for
      certain schedules, maximally for F px px px px px. CY combined to give greater
      than additivity with either cis-DDP or X ray alone, and the combination of CY +
      cis-DDP + X ray appeared to be supra-additive for five different schedules,
      maximally for C x x x x x P. Normal tissue effects are being evaluated for these
      same schedules so that TGF's might soon be obtained.

PMID- 1991684
TI  - Keynote address: a critical assessment of trials of neoadjuvant (preemptive)
      chemotherapy for bladder cancer: lesson for future studies of combined modality
      treatment.
AB  - The 5-year survival of patients with invasive, clinically non-metastatic bladder
      cancer (Stages T2-4N2Mo) is less than 50%, whether treated by radical
      radiotherapy, radical cystectomy, or combinations of the two modalities.
      Cytotoxic regimens, incorporating single agents or combination protocols, produce
      objective response rates of 10-30 and 10-70%, respectively. Hence, it has been
      postulated that the use of cytotoxics before or with radiotherapy or surgery
      ("neoadjuvant", "preemptive", or "concurrent" chemotherapy) could improve the
      cure rate of invasive bladder cancer. Initial Phase I-II clinical trials have
      shown such approaches to be feasible, with mild to moderate toxicity. To date,
      few randomized trials that compare conventional treatment with these new
      approaches have been initiated or completed, with the majority of eligible
      patients being treated in increasingly complex Phase II studies. Accordingly,
      progress has been retarded, and after a decade of investigation, the true role of
      preemptive or concurrent chemotherapy for invasive bladder cancer is not known.
      Patients should be entered into well designed, randomized clinical trials in
      which new approaches to treatment are compared to standard therapy.

PMID- 1991685
TI  - Combined postoperative radiotherapy and weekly cisplatin infusion for locally
      advanced squamous cell carcinoma of the head and neck: preliminary report of a
      randomized trial.
AB  - A prospective clinical trial was designed to evaluate efficacy, toxicity, and
      patient compliance of concomitant postoperative radiotherapy and Cisplatin
      infusion in patients with Stage III or IV S.C.C. of the head and neck and
      histological evidence of extra-capsular spread of tumor in lymph node
      metastase(s). Cisplatin 50 mg IV with forced hydration was given or not every
      week (i.e., 7 to 9 cycles) concurrently with radiotherapy. Between 1984 and 1988,
      83 patients were randomized: 44 were treated by irradiation without chemotherapy
      (RT group) and 39 by the combined modality (CM group). There was no significant
      difference between the two groups in terms of patient characteristics, primary
      sites, tumor differentiation, T.N. stages, or postoperative prognostic factors.
      All patients completed the planned radiotherapy. There were seven severe
      toxicities (greater than grade 3) in the RT group. In the CM group, 30 severe
      toxicities occurred in 16/39 (41%) patients but none was life-threatening. Seven
      of 39 (18%) patients received less than two-thirds of the scheduled Cisplatin
      courses because of intolerance, mainly nausea and vomiting. Preliminary results
      show a better disease-free survival for the CM group (65% at 24 months) than for
      the RT group (41% at 24 months). This significant difference is largely due to
      increased loco-regional control in the CM group (79% vs 59%), the actuarial
      distant metastasis rates in patients controlled above the clavicles not being
      statistically different in the two groups.

PMID- 1991687
TI  - The response of hypoxic cells in SCCVII murine tumors to treatment with cisplatin
      and x rays.
AB  - Possible mechanisms of enhancement of radiation effects by cisplatin, including
      radiosensitization of hypoxic cells, drug-induced tumor reoxygenation, and
      inhibition of repair of sublethal radiation damage, were examined in the murine
      SCCVII model. Combination radiation/drug treatments were most effective when drug
      exposure preceded irradiation of animals breathing a reduced oxygen atmosphere,
      indicating that the primary interaction between the modalities was a cisplatin
      induced increase in the oxygenation status of the acutely hypoxic cells in those
      tumors. Delivering cisplatin prior to or immediately after the first of two 5 Gy
      fractions was more effective than combinations with a single x-ray exposure,
      suggesting that proper sequences of the combined modalities may augment natural
      reoxygenation processes.

PMID- 1991686
TI  - Keynote address: the influence of microenvironmental factors on the activity of
      radiation and drugs.
AB  - The inherent radio- and chemosensitivity of tumor cells clearly affects their
      response to treatment. Accumulating evidence, however, suggests that the
      biochemical and physiological status of the cell during treatment is at least as
      important. In this review, a critique of the current evidence for, and extent of,
      microenvironmental heterogeneity in tumors is presented, emphasizing human tumor
      cells in situ. The expected consequences of those changes on cellular response to
      radiation and chemotherapy is then briefly reviewed. Finally, the continuing
      interest in developing new therapeutic strategies for which the tumor
      microenvironment is an asset (as opposed to a liability) is discussed in the
      context of the dynamic nature of tumors, and the complexity of adequately
      analyzing combination treatments.

PMID- 1991688
TI  - The potential of lactate and succinate to kill nutrient deprived tumor cells by
      intracellular acidification.
AB  - We have investigated the ability of the weak acids, lactate, succinate, and the
      monomethylester of succinate, to cause intracellular acidification of EMT-6 and
      MGH-U1 cells. Each of the three substances caused a decrease of intracellular pH
      (pHi) when the cell lines were exposed at low extracellular pH (pHe) in the range
      6.0-6.5. Only monomethylsuccinate caused intracellular acidification at neutral
      pHe. The fall in pHi increased with increasing dose of each agent and with
      decreasing pHe. The pHi recovered to almost normal values after exposure of 30
      minutes to 50 mM lactate, but there was little or no recovery of pHi in the
      presence of succinate or monomethylsuccinate. Succinate and its methylester were
      toxic to cells at low pHe (less than 6.5), and cell killing increased with
      exposure time and with dose of the agents used. Lactate did not cause cell death
      at low pHe, and none of the three substances exhibited any cytotoxicity at
      neutral pHe. Solid tumors are known to have an acidic microenvironment, and pHe
      may be particularly low in regions of hypoxia. Succinate and its monomethylester
      may have the potential to kill cells in acidic regions of tumors and might
      therefore enhance the effect of radiation.

PMID- 1991689
TI  - Inhibition of recovery from potentially lethal radiation damage in A549 cells by
      the K+/H+ ionophore nigericin.
AB  - A549 cells held for 4 hr in Hank's balanced salt solution, after 10 Gy
      irradiation, exhibit potentially lethal damage recovery (PLDR) which is dependent
      on extracellular pH (pHe). Recovery factors of 2.2 to 3.5 are observed when pHe
      is 6.40 to 7.30, but recovery factors of less than 1.0 are found when pHe is
      reduced to 6.20 or 6.00. The K+/H+ ionophore nigericin, when added to cells post
      irradiation, inhibits PLDR in a pHe-dependent manner; it is increasingly more
      effective as pHe is reduced from 6.80 to 6.40. The presence of nigericin thus
      causes inhibition of PLDR at pHe's that normally promote recovery. The drug does
      not affect radiation response of A549 cells when present only during irradiation.
      Effects of low pHe buffer, with and without nigericin, on intracellular pH (pHi)
      and on ATP levels were examined in an effort to elucidate the mechanisms for
      inhibition of PLDR and enhancement of radiation response. Incubation of cells in
      pHe 6.00 buffer results in a slight decrease in pHi and does not induce a drop in
      ATP levels. In contrast, post-irradiation incubation of cells in pHe 6.40 buffer
      containing 2 microM nigericin causes an immediate and dramatic decrease in pHi,
      and a gradual loss of ATP to 30% of control levels by 4 hr. The data obtained so
      far suggest that a very slight lowering of pHi may influence post-irradiation
      holding recovery, and that the mechanisms by which pHe 6.00 buffer alone, or pHe
      6.40 buffer containing nigericin, affect holding recovery are different.

PMID- 1991690
TI  - Effects of oxygenation and pH on tumor cell response to alkylating chemotherapy.
AB  - In the present investigations we evaluated the consequence of changing the
      cellular microenvironment on the treatment efficacy of the alkylating
      chemotherapeutic agent melphalan. Human A549 adenocarcinoma and mouse KHT/iv
      sarcoma cells were treated with melphalan under aerobic or hypoxic conditions at
      pH 6.6 or 7.4. Both low oxygenation and acidic pH individually were found to
      increase tumor cell killing by this chemotherapeutic agent. However, the
      magnitude of the enhanced toxic effect was greatest when hypoxic conditions and
      acidic pH were combined during treatment. For example, A549 cells treated with
      melphalan under hypoxic conditions at pH 6.6 were approximately 3 times more
      sensitive to this anticancer drug than were cells exposed in air at pH 7.4.
      Conditions of low oxygen and pH also increased the chemosensitization potential
      of the nitroimidazole misonidazole (MISO) when combined with this
      chemotherapeutic agent. Thus, when KHT/iv cells were treated with the combination
      of melphalan plus MISO, the resulting enhancement ratio increased from 1.8 to
      2.5, when the pH maintained during the treatment was changed from physiologic
      (7.4) to acidic (6.6).

PMID- 1991691
TI  - Keynote address: integration of cytostatic agents and radiation therapy: a
      different approach to "proliferating" human tumors.
AB  - Failure to achieve local and regional tumor control with radiation therapy
      remains a significant problem for a number of anatomic sites and can have a
      negative impact upon survival. There is emerging clinical and laboratory evidence
      that proliferation of tumor clonogens during the course of radiation treatment
      significantly impairs local control. Recent in situ studies suggest that as many
      as half of all human carcinomas have the potential to double their cell number in
      5 or fewer days. Thus, cells that survive the initial treatments might rapidly
      repopulate a tumor, resulting in local failure. One potential clinical approach
      to reduce the impact of tumor cell repopulation during treatment would be to
      administer biological or chemical modifiers to slow or inhibit tumor
      proliferation. Examples of these cytostatic modifiers which are available for
      clinical testing now, or in the near future, include hormones, anti-hormones,
      growth factors, growth factor antagonists and other biologicals (e.g.,
      interferons). Clinical alteration of the proliferative status of tumors could
      influence tumor control by reducing the impact of tumor cell proliferation during
      therapy, by modifying tumor cell radiosensitivity, or by favourably altering
      both. To appreciate the magnitude and the cumulative effect of these factors,
      newer technologies and experimental model systems need to be exploited in
      investigating correlations between proliferation and tumor control and between
      proliferative status and radiosensitivity. The design of future clinical trials
      using cytostatic agents and radiotherapy will rely heavily upon such basic
      information.

PMID- 1991692
TI  - Interleukin-1 alpha protects against the toxicity associated with combined
      radiation and drug therapy.
AB  - A dose of total body irradiation sufficient to cause 70% mortality within 30 days
      (9.5 Gy) and maximally tolerated doses of either adriamycin (10 mg/kg) or cis
      dichlorodiammine platinum (8 mg/kg) were administered to C57B1/6 mice and animal
      survival used as an index of toxicity. Whereas the nature of the toxicity
      resulting from the radiation alone was hematopoietic, the addition of either drug
      to the total body irradiation resulted in a pattern of animal death more
      consistent with that of gastrointestinal toxicity (100% dead within 7 days).
      However, if the radiation was delivered as a regional abdominal exposure, rather
      than total body, the gastrointestinal death observed following the combination of
      total body irradiation drug was not observed. The administration of 2.5 x 10(5) U
      IL-1 v24 hr prior to total body irradiation demonstrated significant protection
      against this dose of radiation (90% survival vs 30% survival). Similar protection
      was also observed when the IL-1 was administered 24 hr prior to the combination
      of total body irradiation with either drug. While these observations suggested
      that the IL-1 was protecting against gastrointestinal toxicity, subsequent
      studies demonstrated that IL-1, in addition to accelerating hematopoietic
      recovery following radiation insult, was equally effective in advancing the
      repopulation of the stem cell (CFU-GEMM) and progenitor cell (CFU-M and CFU-GM)
      compartments following drug treatment. Collectively, the data from these studies
      demonstrate that the lethal effects resulting from combined total body
      irradiation + drug treatment contain both a gastrointestinal and a hematopoietic
      component.

PMID- 1991693
TI  - Altered radioprotective properties of interleukin I alpha (IL-1) in non
      hematologic tumor-bearing animals.
AB  - The radioprotective properties of IL-1 were investigated in the respective murine
      hosts for the Lewis lung (LLca) and EMT-6 tumors. For these studies, doses of
      total body irradiation were selected for the C57B1/6 (9.5 Gy) and Balb/c (7.5 Gy)
      mice that resulted in a 60% mortality over a 30-day interval. When a "priming"
      dose of 2.5 x 10(5) U IL-1 was administered 24 hr prior to the radiation
      exposure, animal mortality was markedly reduced (60% vs 5-10%). Under identical
      experimental conditions, however, the presence of either the LLca or the EMT-6
      tumors in their respective host strains was found to compromise the level of
      radioprotection conferred by this priming dose of IL-1. In Balb/c mice bearing
      the EMT-6 tumor, a priming dose of IL-1 resulted in only a modest level of
      radioprotection when compared to non-tumor-bearing control animals (median animal
      survival increased by 11.5 days). In C57B1/6 mice bearing the LLca tumor, IL-1
      failed to demonstrate any evidence of radioprotection. Following a sublethal dose
      of total body irradiation, the appearance of an accelerated repopulation of the
      stem cell (8d CFUs and CFU-GEMM) and the myeloid progenitor (CFU-M) compartment
      in the marrow of the IL-1 primed EMT-6, but not the LLca, tumor-bearing animals
      was consistent with the hypothesis that the mechanism leading to radioprotection
      in IL-1 primed rodents involves an accelerated recovery of hematopoietic
      activity. It was also noted that the presence of the EMT-6 tumor was associated
      with an increase in the "radiosensitivity" of the Balb/c mouse. Collectively,
      these data suggest that the use of biological modifiers should be examined under
      altered physiological conditions prior to attempting to translate them into the
      clinic.

PMID- 1991694
TI  - Interleukin-1 modification of the effects of cyclophosphamide and fractionated
      irradiation.
AB  - Studies were performed to determine whether recombinant human interleukin-1 (IL
      1) modifies the tumor cytotoxicity of cyclophosphamide (CY) combined with
      fractionated X-irradiation. RIF-1 tumors were implanted intradermally in C3H/Km
      mice and therapeutic effect was evaluated by the regrowth delay method, that is,
      the time for treated tumors to grow to 3 times their volume at the start of
      treatment relative to that for untreated tumors. A single intraperitoneal
      treatment of 15 micrograms/kg IL-1 given 24 hr after 100 or 200 mg/kg CY and
      immediately before the first of 5 daily fractionated treatments of 1-4 Gy
      increased tumor growth delay beyond that produced by CY and irradiation without
      the IL-1. However, the IL-1 given with either CY or fractionated irradiation did
      not extend the time for tumor regrowth beyond that produced by the agents
      themselves. Thus, while CY and fractionated irradiation together produce a
      greater than additive effect, IL-1 seems to extend this phenomenon. From these
      findings, it appears that IL-1 enhances the cytotoxic effects of CY and X ray
      against tumors, an effect that would have considerable practical significance in
      the light of the protective effects shown elsewhere for the same lymphokine on
      normal tissues.

PMID- 1991695
TI  - Epidermal growth factor modification of radioresistance related to cell-cell
      interactions.
AB  - The effect of epidermal growth factor on radiosensitivity of cells in spheroids
      and its relationship to radioresistance associated with cell-cell interactions
      was examined. A human squamous carcinoma cell lines, CaSki, was used. Epidermal
      growth factor present for 48 hr before irradiation reduced the plating efficiency
      but did not affect the radiosensitivity of cells. However, epidermal growth
      factor present after irradiation, that is, during the period of colony formation,
      reduced the plating efficiency and increased the radiosensitivity of cells from
      spheroids. Both effects were maximum at 10 ng/ml epidermal growth factor. The
      enhancement in radiation response was not related to epidermal growth factor
      effects on potentially lethal and sublethal damage repair. In the absence of cell
      cell interactions, such as monolayer cultures and spheroids disaggregated for 15
      hr before irradiation, radiosensitivity enhancement by epidermal growth factor
      was associated with reduced shoulder of the cell survival curve. However, in the
      presence of cell-cell interactions, such as intact spheroids and spheroids
      disaggregated immediately before irradiation, in addition to reduced shoulder,
      epidermal growth factor treatment increased the slope compared to that of the
      monolayer cultures. The results indicate that epidermal growth factor enhances
      cellular radiosensitivity and modifies effects of cell-cell interactions.

PMID- 1991696
TI  - Keynote address: modulation of normal tissue toxicity by combined modality
      therapy: considerations for improving the therapeutic gain.
AB  - The aim of combined modality treatment schedules is to achieve increased killing
      in the tumor cell populations without an equivalent increase in normal tissue
      damage. There is, however, some increased risk of normal tissue toxicity that
      must be taken into account when assessing the therapeutic potential. An
      understanding of the mechanisms involved in combined modality therapy, for
      example, increased radiosensitivity, inhibition or stimulation of cellular
      proliferation, or independent additive toxicities, should improve the chances of
      of achieving a therapeutic gain. A review of the literature of normal tissue
      effects after combined treatment with drugs and radiation has lead to the
      following general conclusions: a) The sequence and timing of the two agents have
      a marked influence on the extent of normal tissue damage, with the most damage
      occurring when simultaneous drug and irradiation are given within a few days of
      each other; b) Separation of the two modalities can lead to an improved
      therapeutic gain since tumor effects are less strongly dependent on the interval
      between drug and X rays; and c) Chemotherapy can markedly alter the time of
      expression of radiation damage, particularly in slowly dividing normal tissues,
      where more rapid expression of injury occurs after combined modality therapy. The
      above concepts and some possible ways for improving the therapeutic gain in
      future trials are discussed in this review.

PMID- 1991697
TI  - Early and late effects of cisplatin and radiation at acute and low dose rates on
      the mouse skin and soft tissues of the leg.
AB  - The influence of radiation dose rate and drug dose on the combined effects of
      cisplatin (Cis-diamminedichloroplatinum (II] and radiation on the skin and soft
      tissues was studied in the C3Hf/SED mice. Localized acute-dose-rate irradiation
      (ADRI) at 3.345 Gy/min and continuous low-dose-rate irradiation (CLDRI) of the
      hind leg at 0.028 Gy/min with and without the drug was delivered using a 137Cs
      laboratory irradiator. Cisplatin at 6 or 11 mg/kg was given by intraperitoneal
      bolus injection 1 hour before ADRI or by continuous infusion during CLDRI. Acute
      skin reaction was scored from days 13 to 30 and late skin contraction and leg
      contracture were measured at days 90, 180, 270, and 360 after treatment. A marked
      dose-rate effect was observed for these early and late normal tissue endpoints.
      At a dose of 60 Gy of CLDRI, the dose rate factor (DRF = isoeffect dose at
      CLDRI/isoeffect dose at ADRI) was 1.82 for acute skin reaction and 1.76 for late
      skin contraction or leg contracture at day 270. However, there was no significant
      enhancement of these early and late normal tissue effects by cisplatin at 6 or 11
      mg/kg at either acute or low dose rates. Thus neither drug dose nor radiation
      dose rate had a significant impact on the combined effects of cisplatin and
      radiation on the mouse skin and soft tissues of the leg.

PMID- 1991698
TI  - Influence of nephrotoxic drugs on the late renal toxicity associated with bone
      marrow transplant conditioning regimens.
AB  - The total body irradiation that is given as part of bone marrow transplant
      conditioning regimens is a factor in the renal toxicity that is observed after
      bone marrow transplant, but it may not be the only factor. We hypothesize that
      nephrotoxic drugs used in prior chemotherapy can precipitate renal radiation
      damage. Studies were designed to determine if nephrotoxic antineoplastic drugs
      could shorten the latent period for the development of radiation nephritis. Rats
      were given bilateral renal irradiation using a radiation schedule that produced
      moderate nephritis. Cisplatinum, BCNU, or mitomycin were given before, during, or
      after irradiation at doses that produced only mild nephrotoxicity. All
      cisplatinum-radiation sequences resulted in decreased renal function, with
      radiation prior to cisplatinum producing the greatest dysfunction. BCNU increased
      renal dysfunction equally in all schedules, but mitomycin had only minimal
      effects. Most drug schedules, including those with mitomycin, produced earlier
      development of morbidity after fractionated renal irradiation. In a second set of
      studies, rats were given single doses of the same nephrotoxic drugs, followed 3
      months later by total body irradiation plus bone marrow transplant. The drugs had
      no effect on the marrow ablation dose, but BCNU and cisplatinum decreased
      gastrointestinal tolerance. Four months after total body irradiation, rats which
      received drugs alone or total body irradiation alone have essentially normal
      renal function, but rats which received cisplatinum plus total body irradiation
      or BCNU plus total body irradiation show a dose-dependent decrease in renal
      function. These studies show that radiation nephritis can be precipitated by low
      doses of nephrotoxic drugs, and may help to explain the incidence of early
      radiation nephritis in bone marrow transplant patients conditioned with total
      body irradiation.

PMID- 1991699
TI  - Radiosensitivity of jejunal mucosa after whole abdomen irradiation and CDDP
      pretreatment.
AB  - Pretreatment of mice with a single radiation dose of 11.5 Gy or with fractionated
      irradiation (2 x 6.5 or 7.5 Gy, with an interval time of 12 hr) led to a relative
      decrease in the radiosensitivity of jejunal crypt cells when a second single dose
      of radiation was delivered 2 months later. When the same irradiation pretreatment
      was combined with CDDP (6 mg/kg, i.p.) injected 12 hr after single radiation or
      between two equal doses of radiation, similar crypt cells resistance was
      obtained. The combination of CDDP with irradiation did not modify the
      radiosensitivity of jejunal crypts in comparison with irradiation alone, even
      when the total radiation dose was delivered in 2 split doses. This induced
      radioresistance was demonstrated to be a reflection of late injury on intestinal
      tissue, presumably due to hypoxia resulting from vascular damage. It seems that
      the administration of CDDP did not change the possible hypoxia suspected in crypt
      cells of mice pretreated with single radiation dose. However, mouse lethality
      increased significantly when CDDP was combined with irradiation.

PMID- 1991700
TI  - Concomitant evaluation of efficiency, acute and delayed toxicities of combined
      treatment of radiation and CDDP on an in vivo model.
AB  - The efficiency, acute and delayed toxicities of different radio-chemotherapeutic
      combinations were assessed on an in vivo model (Krebs II ascitic carcinoma
      grafted to female Swiss mice). Mice were given whole abdomen irradiation (WAI)
      2.5 to 10 Gy as a single dose (WAI). CDDP was given intraperitoneally at 0.5 to 4
      mg/kg dose level, 12 hr before or after WAI. There was a relationship between
      dose of CDDP and increase of life span (ILS) of mice. However, WAI did not
      increase the life span. When a single dose of 2 mg/kg CDDP was given prior to a
      2.5 Gy WAI, the ILS reached 47%. By contrast, it was only 37% when treatment
      sequence was reversed. When the WAI dose level was increased to 5 Gy, the ILS was
      not increased. The jejunal crypt cell number, determined 3 days after the last
      treatment, was not modified, regardless of the treatment sequence. There was no
      delayed renal toxicity. The study on the Krebs II ascites model confirms the
      tumor cell therapeutic potentiation without exacerbation of normal tissue damage.

PMID- 1991701
TI  - A phase I study of prolonged infusion 5-fluorouracil and concomitant radiation
      therapy in patients with squamous cell cancer of the head and neck.
AB  - The radiosensitization properties of 5-FU are well documented, and clinical
      trials have suggested improved local control and survival in head and neck
      cancer. Clinical trials to date have used bolus injection or short term (less
      than or equal to 5 days) 5-FU infusions. To determine the maximum tolerated dose
      (MTD) of 5-FU given as continuous intravenous infusion for 12 weeks concomitant
      with conventional radiation therapy, 18 patients with advanced inoperable head
      and neck cancers were treated with conventional irradiation and 100, 200, 250, or
      300 mg/m2/day of 5-FU. A dose of 250 mg/m2/day was determined to be the maximum
      tolerated dose and is recommended for Phase II studies.

PMID- 1991702
TI  - Marrow antioxidant enzyme activity in tumor-bearing and non-tumor-bearing mice
      following vincristine treatment.
AB  - Pretreatment or "priming" with vincristine (VcR) has been documented to
      radioprotect animals from whole body irradiation by accelerating recovery of
      hematopoietic marrow. The mechanisms underlying this phenomenon are unclear, but
      the marked similarities between priming with VcR and with immune stimulants such
      as endotoxin and glucan have led to speculation that VcR may be inducing such
      radioprotective immunoregulators as interleukin 1 (IL-1) and tumor necrosis
      factor (TNF). The radioprotective ability of these cytokines, in turn, has been
      linked to an induction of the antioxidant enzyme manganese superoxide dismutase
      (Mn SOD). To establish whether priming with VcR is associated with induction of
      antioxidant enzymes, the activities of Mn SOD, copper-zinc (Cu-Zn) SOD, catalase
      (CAT), and glutathione peroxidase (GPX) were measured in the marrow of both LLca
      tumor-bearing and non-tumor-bearing mice given a priming dose of VcR. Results in
      non-tumor-bearing mice indicate that, similar to IL-1 and TNF administration, VcR
      treatment increases Mn-SOD activity, but not Cu-Zn SOD, CAT, or GPX activity.
      Furthermore, this increase occurs at the time VcR priming has been demonstrated
      previously to exhibit maximal radioprotection, suggesting that it may be
      contributing factor. However, VcR priming has been demonstrated to radioprotect
      both tumor-bearing and non-tumor-bearing animals, and no increase in Mn SOD
      activity (or the other enzymes monitored) was found in the tumor-bearing group.
      Rather, the presence of tumor significantly suppressed antioxidant enzyme
      activity. Collectively, the present data suggest that it is unlikely that
      increased antioxidant enzyme activity is directly involved in the VcR priming
      response.

PMID- 1991703
TI  - Activity of etoposide (VP-16) in human tumor cells under different growth
      conditions.
AB  - The effect of etoposide (VP-16) on a human epidermoid carcinoma cell line (HEp3)
      has been evaluated under different growth conditions. A significant increase in
      resistance to this agent from exponential to unfed plateau cells has been
      observed. Variations in the cell cycle distribution appear not to be sufficient
      to explain the difference in cell killing. Rather, our studies suggest the
      presence of an important proportion of quiescent (Q) cells in the plateau phase
      cultures which may determine the treatment outcome.

PMID- 1991704
TI  - The effects of leucovorin and dipyridamole on fluoropyrimidine-induced
      radiosensitization.
AB  - The biomodulators leucovorin and dipyridamole potentiate the cytotoxicity of 5
      fluorodeoxyuridine (FdUrd) and 5-fluorouracil (5-FU), respectively. It was
      hypothesized that these biomodulators would increase fluoropyrimidine-mediated
      radiosensitization. This hypothesis was tested using cultured HT29 human colon
      cancer cells. As was predicted, leucovorin increased both FdUrd-mediated
      cytotoxicity and radiosensitization. The increase in radiation sensitivity was
      associated with a decrease in the repair of radiation-induced DNA double strand
      breaks (DSB's). Dipyridamole potentiated the cytotoxicity produced by 5-FU.
      However, dipyridamole appeared to confer slight protection from irradiation, thus
      decreasing 5-FU-mediated radiosensitization. This demonstrates that the simple
      fact that a biomodulator can increase fluoropyrimidine-induced cytotoxicity does
      not guarantee a corresponding increase in radiation sensitivity. Clinical trials
      combining fluoropyrimidines and their biomodulators will need to take these
      potentially complex interactions into account.

PMID- 1991705
TI  - American Society of Andrology 16th annual meeting. Program and abstracts. April
      27-30, 1991.

PMID- 1991706
TI  - Deletion analysis of the F plasmid oriT locus.
AB  - Functional domains of the Escherichia coli F plasmid oriT locus were identified
      by deletion analysis. DNA sequences required for nicking or transfer were
      revealed by cloning deleted segments of oriT into otherwise nonmobilizable pUC8
      vectors and testing for their ability to promote transfer or to be nicked when
      tra operon functions were provided in trans. Removal of DNA sequences to the
      right of the central A + T-rich region (i.e., from the direction of traM) did not
      affect the susceptibility of oriT to nicking functions; however, transfer
      efficiency for oriT segments deleted from the right was progressively reduced
      over an 80- to 100-bp interval. Deletions extending toward the oriT nick site
      from the left did not affect the frequency of transfer if deletion endpoints lay
      at least 22 bp away from the nick site. Deletions or insertions in the central, A
      + T-rich region caused periodic variation in transfer efficiency, indicating that
      phase relationships between nicking and transfer domains of oriT must be
      preserved for full oriT function. These data show that the F oriT locus is
      extensive, with domains that individually contribute to transfer, nicking, and
      overall structure.

PMID- 1991707
TI  - Salmonella typhimurium has two homologous but different umuDC operons: cloning of
      a new umuDC-like operon (samAB) present in a 60-megadalton cryptic plasmid of S.
      typhimurium.
AB  - Expression of the umuDC operon is required for UV and most chemical mutagenesis
      in Escherichia coli. The DNA which can restore UV mutability to a umuD44 strain
      and to a umuC122::Tn5 strain of E. coli has been cloned from Salmonella
      typhimurium TA1538. DNA sequence analysis indicated that the cloned DNA
      potentially encoded proteins with calculated molecular weights of 15,523 and
      47,726 and was an analog of the E. coli umuDC operon. We have termed this cloned
      DNA the samAB (for Salmonella mutagenesis) operon and tentatively referred to the
      umuDC operon of S. typhimurium LT2 (C. M. Smith, W. H. Koch, S. B. Franklin, P.
      L. Foster, T. A. Cebula, and E. Eisenstadt, J. Bacteriol. 172:4964-4978, 1990; S.
      M. Thomas, H. M. Crowne, S. C. Pidsley, and S. G. Sedgwick, J. Bacteriol.
      172:4979-4987, 1990) as the umuDCST operon. The samAB operon is 40% diverged from
      the umuDCST operon at the nucleotide level. Among five umuDC-like operons so far
      sequenced, i.e., the samAB, umuDCST, mucAB, impAB, and E. coli umuDC operons, the
      samAB operon shows the highest similarity to the impAB operon of TP110 plasmid
      while the umuDCST operon shows the highest similarity to the E. coli umuDC
      operon. Southern hybridization experiments indicated that (i) S. typhimurium LT2
      and TA1538 had both the samAB and the umuDCST operons and (ii) the samAB operon
      was located in a 60-MDa cryptic plasmid. The umuDCST operon is present in the
      chromosome. The presence of the two homologous but different umuDC operons may be
      involved in the poor mutability of S. typhimurium by UV and chemical mutagens.

PMID- 1991708
TI  - Mini-F plasmid mutants able to replicate in the absence of sigma 32: mutations in
      the repE coding region producing hyperactive initiator protein.
AB  - Mini-F plasmids cannot replicate in Escherichia coli strains (delta rpoH) lacking
      sigma 32, presumably because transcription of the repE gene encoding the
      replication initiator protein (RepE protein) depends mostly on RNA polymerase
      containing sigma 32. We have isolated and characterized mini-F mutants able to
      replicate in delta rpoH cells. Contrary to the initial expectation, five mutants
      with mutations in the repE coding region that produce altered RepE proteins were
      obtained. The mutations caused replacement of a single amino acid: the 92nd
      glutamic acid was replaced by lysine (repE10, repE16, and repE25) or glycine
      (repE22) or the 109th glutamic acid was replaced by lysine (repE26). These
      plasmids overproduced RepE protein and exhibited very high copy numbers. Two
      major activities of mutated RepE proteins have been determined in vivo; the
      autogenous repressor activity was significantly reduced, whereas the initiator
      activity was much enhanced in all mutants. These results indicate the importance
      of a small central region of RepE protein for both initiator and repressor
      activities. Thus the decreased repE transcription in delta rpoH cells can be
      compensated for by an increased initiator activity and a decreased repressor
      activity of RepE, resulting in the increased synthesis of hyperactive RepE
      protein.

PMID- 1991709
TI  - Pseudomonas syringae pv. phaseolicola genomic clones harboring heterologous DNA
      sequences suppress the same phaseolotoxin-deficient mutants.
AB  - Cosmid cloning and mutagenesis were used to identify genes involved in the
      production of phaseolotoxin, the chlorosis-inducing phytotoxin of Pseudomonas
      syringae pv. phaseolicola, the causal agent of halo blight of bean (Phaseolus
      vulgaris L.). Eight stable clones were isolated from a genomic cosmid library by
      en masse mating to 10 ethyl methanesulfonate (EMS)-induced Tox- mutants. In cross
      matings, each suppressed all 10 mutants as well as an additional 70 EMS-induced
      Tox- mutants (and one UV-induced Tox- mutant). On the basis of restriction
      endonuclease analysis and hybridization studies, the clones were grouped into
      three classes. Clones in a particular class shared common fragments, whereas
      clones in different classes did not. Clones from class I (but not classes II and
      III) also suppressed Tn5-induced Tox- mutants. Interposon mutagenesis and marker
      exchange of a representative clone from class III into the wild-type genome did
      not alter its Tox+ phenotype, indicating that this clone does not harbor
      structural or regulatory genes involved in phaseolotoxin production. We suggest
      that the genome of P. syringae pv. phaseolicola contains a "hot spot" in one of
      the functions involved in toxin production which is affected by EMS and UV and
      that heterologous clones are able to suppress the Tox- phenotype because their
      inserts encode products that are able to substitute for the product of the
      mutated gene. Alternatively, the inserts may contain sequences which titrate a
      repressor protein. In either case, the data suggest that suppression of EMS- and
      UV-induced mutants occurs when heterologous clones are present in multiple
      copies.

PMID- 1991710
TI  - Metronidazole activation and isolation of Clostridium acetobutylicum electron
      transport genes.
AB  - An Escherichia coli F19 recA, nitrate reductase-deficient mutant was constructed
      by transposon mutagenesis and shown to be resistant to metronidazole. This mutant
      was a most suitable host for the isolation of Clostridium acetobutylicum genes on
      recombinant plasmids, which activated metronidazole and rendered the E. coli F19
      strain sensitive to metronidazole. Twenty-five E. coli F19 clones containing
      different recombinant plasmids were isolated and classified into five groups on
      the basis of their sensitivity to metronidazole. The clones were tested for
      nitrate reductase, pyruvate-ferredoxin oxidoreductase, and hydrogenase
      activities. DNA hybridization and restriction endonuclease mapping revealed that
      four of the C. acetobutylicum insert DNA fragments on recombinant plasmids were
      linked in an 11.1-kb chromosomal fragment. DNA sequencing and amino acid homology
      studies indicated that this DNA fragment contained a flavodoxin gene which
      encoded a protein of 160 amino acids that activated metronidazole and made the E.
      coli F19 mutant very sensitive to metronidazole. The flavodoxin and hydrogenase
      genes which are involved in electron transfer systems were linked on the 11.1-kb
      DNA fragment from C. acetobutylicum.

PMID- 1991711
TI  - Thermosensing ability of Trg and Tap chemoreceptors in Escherichia coli.
AB  - The thermosensing ability of the Trg and Tap chemoreceptors in Escherichia coli
      was investigated after amplifying these receptors in a host strain lacking all
      four known chemoreceptors (Tar, Tsr, Trg, and Tap). Cells with an increased
      amount of either Trg or Tap showed mostly smooth swimming and no response to
      thermal stimuli. However, when the smooth-swimming bias of the cells was reduced
      by adding Trg- or Tap-mediated repellents, the cells showed clear changes in the
      swimming pattern upon temperature changes; Trg-containing cells showed tumbling
      at 23 degrees C but mostly smooth swimming at 32 degrees C, while Tap-containing
      cells showed smooth swimming at 20 degrees C but tumbling at 32 degrees C. These
      results indicate that although both Trg and Tap have the ability to sense thermal
      stimuli, Trg functions as a warm receptor, as reported previously for Tar and
      Tsr, while Tap functions as a cold receptor.

PMID- 1991713
TI  - Controlled expression of the transcriptional activator gene virG in Agrobacterium
      tumefaciens by using the Escherichia coli lac promoter.
AB  - The Agrobacterium VirG protein is normally expressed from two promoters in
      response to multiple stimuli, including plant-released phenolics (at promoter P1)
      and acidic growth media (at promoter P2). To simplify the analysis of vir gene
      induction, we sought to create Agrobacterium strains in which virG could be
      expressed in a controllable fashion. To study the possibility of using the lac
      promoter and repressor, we constructed a plasmid containing the lac promoter
      fused to the lacZ structural gene. A derivative of this plasmid containing the
      lacIq gene was also constructed. The plasmid not containing lacIq expressed high
      levels of beta-galactosidase. The plasmid containing lacIq expressed beta
      galactosidase at very low levels in the absence of o-nitrophenyl-beta-D
      galactoside (IPTG) and at moderate levels in the presence of IPTG. We also fused
      the lac promoter to a virG::lacZ translational fusion and found that IPTG
      elevated expression of this translational fusion to moderate levels, though not
      to levels as high as from the stronger of the two native virG promoters. Finally,
      the lac promoter was used to express the native virG gene in strains containing a
      virB::lacZ translational fusion. virB expression in this strain depended on
      addition of IPTG as well as the vir gene inducer acetosyringone. In a similar
      strain lacking lacIq, virB expression was greater than in a strain in which virG
      was expressed from its native promoters. Expression of virG from the lac promoter
      did not alter the acidic pH optimum for vir gene induction, indicating that the
      previously observed requirement for acidic media was not due solely to the need
      to induce P2.

PMID- 1991712
TI  - Bradyrhizobium japonicum has two differentially regulated, functional homologs of
      the sigma 54 gene (rpoN).
AB  - Recognition of -24/-12-type promoters by RNA polymerase requires a special sigma
      factor, sigma 54 (RpoN NtrA GlnF). In the nitrogen-fixing soybean symbiont
      Bradyrhizobium japonicum, two functional, highly conserved rpoN genes (rpoN1 and
      rpoN2) were identified and sequenced. The two predicted B. japonicum RpoN protein
      sequences were 87% identical, and both showed different levels of homology to the
      RpoN proteins of other bacteria. Downstream of rpoN2 (but not of rpoN1), two
      additional open reading frames were identified that corresponded to open reading
      frames located at similar positions in Klebsiella pneumoniae and Pseudomonas
      putida. Both B. japonicum rpoN genes complemented the succinate- and nitrate
      negative phenotypes of a Rhizobium meliloti rpoN mutant. B. japonicum strains
      carrying single or double rpoN mutations were still able to utilize C4
      dicarboxylates as a carbon source and histidine, proline, or arginine as a
      nitrogen source, whereas the ability to assimilate nitrate required expression of
      at least one of the two rpN genes. In symbiosis both rpoN genes could replace
      each other functionally. The rpoN1/2 double mutant induced about twice as many
      nodules on soybeans as did the wild type, and these nodules lacked nitrogen
      fixation activity completely. Transcription of a nifH'-'lacZ fusion was not
      activated in the rpoN1/2 mutant background, whereas expression of a fixR'-'lacZ
      fusion in this mutant was affected only marginally. By using rpoN'-'lacZ fusions,
      rpoN1 expression was shown to be activated at least sevenfold in microaerobiosis
      as compared with that in aerobiosis, and this type of regulation involved fixLJ.
      Expression of rpoN2 was observed under all conditions tested and was increased
      fivefold in an rpoN2 mutant. The data suggested that the rpoN1 gene was regulated
      in response to oxygen, whereas the rpoN2 gene was negatively autoregulated.

PMID- 1991714
TI  - Identification of three amino acid residues in the B subunit of Shiga toxin and
      Shiga-like toxin type II that are essential for holotoxin activity.
AB  - Shiga toxin of Shigella dysenteriae type I and Shiga-like toxins I and II (SLT-I
      and SLT-II, respectively) of enterohemorrhagic Escherichia coli are functionally
      similar protein cytotoxins. These toxin molecules have a bipartite molecular
      structure which consists of an enzymatically active A subunit that inhibits
      protein synthesis in eukaryotic cells and an oligomeric B subunit that binds to
      globotriaosylceramide glycolipid receptors on eukaryotic cells. Regionally
      directed chemical mutagenesis of the B subunit of SLT-II was used to identify
      amino acids in the B subunit that are critical for SLT-II holotoxin cytotoxic
      activity. Three noncytotoxic mutants were isolated, and their mutations were
      mapped. The substitutions of arginine with cysteine at codon 32, alanine with
      threonine at codon 42, and glycine with aspartic acid at codon 59 in the 70-amino
      acid mature SLT-II B polypeptide resulted in the complete abolition of
      cytotoxicity. The analogous arginine, alanine, and glycine residues were
      conserved at codons 33, 43, and 60 in the 69-amino-acid mature B polypeptide of
      Shiga toxin. Comparable mutations induced in the B-subunit gene of Shiga toxin by
      oligonucleotide-directed, site-specific mutagenesis resulted in drastically
      decreased cytotoxicity (10(3)- to 10(6)-fold) as compared with that of wild-type
      Shiga toxin. The mutant SLT-II and Shiga toxin B subunits were characterized for
      stability, receptor binding, immunoreactivity, and ability to be assembled into
      holotoxin.

PMID- 1991715
TI  - A transcription terminator in the thymidylate synthase (thyA) structural gene of
      Escherichia coli and construction of a viable thyA::Kmr deletion.
AB  - A transcription terminator has been identified within the coding sequence of the
      Escherichia coli thyA gene. Fusion of a relevant segment of the thyA structural
      gene to galK sequences showed that the terminator functions in vivo. Primer
      extension and Northern hybridization (RNA blot) analysis of thyA RNA suggested
      that the terminator acts as the transcription stop signal for an upstream gene
      and for thyA-specific transcripts. Results from antitermination studies utilizing
      a lambda PL-thyA fusion also offer evidence that the terminator is capable of
      attenuating thyA expression by reducing the amount of full-length thyA
      transcripts. This gene arrangement suggested that previous unsuccessful attempts
      to create a chromosomal thyA deletion in E. coli were attributable to the
      presence of the overlapping transcript. Introducing a deletion into the
      nonoverlapping portion of the cloned thyA gene and inserting a gene encoding
      kanamycin resistance produced a (delta thyA::Kmr) that was easily transferred to
      the chromosome of a recD host by marker replacement. This delta thyA::Kmr allele
      provides a useful and readily transducible chromosomal marker.

PMID- 1991716
TI  - Mutagenic frequencies of site-specifically located O6-methylguanine in wild-type
      Escherichia coli and in a strain deficient in ada-methyltransferase.
AB  - The adaptive response of Escherichia coli involves protection of the cells
      against the toxic and mutagenic consequences of exposure to high doses of a
      methylating agent by prior exposure to low doses of the agent. Ada protein, a
      major repair activity for O6-methylguanine, is activated to positively control
      the adaptive response; O6-methylguanine is one of the major mutagenic lesions
      produced by methylating agents. We investigated the mutation frequency of wild
      type Escherichia coli and strains containing the ada-5 mutation in response to
      site-specifically synthesized O6-methylguanine under conditions in which the
      adaptive response was not induced. Site-directed mutagenesis and oligonucleotide
      self-selection techniques were used to isolate the progeny of M13mp18 DNAs
      constructed to contain O6-methylguanine at any of eight different positions. The
      progeny were isolated from E. coli strains isogeneic except for deficiency in Ada
      methyltransferase repair, UvrABC excision repair, or both. The resulting O6
      methylguanine mutation levels at each position were determined by using
      differential oligonucleotide hybridization. We found that the wild type had up to
      a 2.6-fold higher mutation frequency than ada-5 mutants. In addition, the
      mutation frequency varied with the position of the O6-methylguanine in the DNA in
      the wild type but not in ada-5 mutants; O6-methylguanine lesions at the 5' ends
      of runs of consecutive guanines gave the highest mutation frequencies.
      Determination of the mutation frequency of O6-methylguanine in wild-type and mutS
      cells showed that mismatch repair can affect O6-methylguanine mutation levels.

PMID- 1991717
TI  - The ompH gene of Yersinia enterocolitica: cloning, sequencing, expression, and
      comparison with known enterobacterial ompH sequences.
AB  - We have recently described a previously uncharacterized outer membrane protein of
      Salmonella typhimurium and Escherichia coli and cloned and sequenced the
      corresponding gene, the ompH gene, of S. typhimurium (P. Koski, M. Rhen, J.
      Kantele, and M. Vaara, J. Biol. Chem. 264:18973-18980, 1989). We report here the
      cloning, sequencing, and expression of the corresponding gene of Yersinia
      enterocolitica. It is significantly homologous to the ompH genes of E. coli and
      S. typhimurium (homology percentages, 65 and 64%, respectively), has a promoter
      region strongly homologous to the E. coli 17-bp class consensus promoter, and
      encodes a protein consisting of 165 amino acids (22 of which form the signal
      sequence). The plasmid-borne Y. enterocolitica ompH was found to be expressed
      both in the E. coli host and in minicells. The isolated outer membrane of Y.
      enterocolitica was shown to contain OmpH. The homology of the Y. enterocolitica
      OmpH protein is 66% with E. coli OmpH and 64% with S. typhimurium OmpH. All OmpH
      proteins have almost identical hydrophobic profiles, charge distributions, and
      predicted secondary structures. Because yersiniae are considered rather distant
      relatives of E. coli and S. typhimurium in the Enterobacteriaceae family, these
      results might indicate that most or all strains of the family Enterobacteriaceae
      have OmpH proteins remarkably homologous to those now sequenced.

PMID- 1991718
TI  - Novel organization of the common nodulation genes in Rhizobium leguminosarum bv.
      phaseoli strains.
AB  - Nodulation by Rhizobium, Bradyrhizobium, and Azorhizobium species in the roots of
      legumes and nonlegumes requires the proper expression of plant genes and of both
      common and specific bacterial nodulation genes. The common nodABC genes form an
      operon or are physically mapped together in all species studied thus far.
      Rhizobium leguminosarum bv. phaseoli strains are classified in two groups. The
      type I group has reiterated nifHDK genes and a narrow host range of nodulation.
      The type II group has a single copy of the nifHDK genes and a wide host range of
      nodulation. We have found by genetic and nucleotide sequence analysis that in
      type I strain CE-3, the functional common nodA gene is separated from the nodBC
      genes by 20 kb and thus is transcriptionally separated from the latter genes.
      This novel organization could be the result of a complex rearrangement, as we
      found zones of identity between the two separated nodA and nodBC regions.
      Moreover, this novel organization of the common nodABC genes seems to be a
      general characteristic of R. leguminosarum bv. phaseoli type I strains. Despite
      the separation, the coordination of the expression of these genes seems not to be
      altered.

PMID- 1991719
TI  - Isolation and characterization of ilvA, ilvBN, and ilvD mutants of Caulobacter
      crescentus.
AB  - Caulobacter crescentus strains requiring isoleucine and valine (ilv) for growth
      were shown by transduction and pulsed-field gel electrophoresis to contain
      mutations at one of two unlinked loci, ilvB and ilvD. Other C. crescentus strains
      containing mutations at a third locus, ilvA, required either isoleucine or
      methionine for growth. Biochemical assays for threonine deaminase,
      acetohydroxyacid synthase, and dihydroxyacid dehydratase demonstrated that the
      ilvA locus encodes threonine deaminase, the ilvB locus encodes acetohydroxyacid
      synthase, and the ilvD locus encodes dihydroxyacid dehydratase. C. crescentus
      strains resistant to the herbicide sulfometuron methyl, which is known to inhibit
      the action of certain acetohydroxyacid synthases in a variety of bacteria and
      plants, were shown to contain mutations at the ilvB locus, further suggesting
      that an acetohydroxyacid synthase gene resides at this locus. Two recombinant
      plasmids isolated in our laboratory, pPLG389 and pJCT200, were capable of
      complementing strains containing the ilvB and ilvD mutations, respectively. The
      DNA in these plasmids hybridized to the corresponding genes of Escherichia coli
      and Serratia marcescens, confirming the presence of ilvB-like and ilvD-like DNA
      sequences at the ilvB and ilvD loci, respectively. However, no hybridization was
      observed between any of the other enteric ilv genes and C. crescentus DNA. These
      results suggest that C. crescentus contains an isoleucine-valine biosynthetic
      pathway which is similar to the corresponding pathway in enteric bacteria but
      that only the ilvB and ilvD genes contain sequences which are highly conserved at
      the DNA level.

PMID- 1991722
TI  - p-cresol methylhydroxylase from a denitrifying bacterium involved in anaerobic
      degradation of p-cresol.
AB  - A bacterium, strain PC-07, previously isolated as part of a coculture capable of
      growing on p-cresol under anaerobic conditions with nitrate as the acceptor was
      identified as an Achromobacter sp. The first enzyme of the pathway, p-cresol
      methylhydroxylase, which converts its substrate into p-hydroxybenzyl alcohol, was
      purified. The enzyme had an Mr of 130,000 and the spectrum of a flavocytochrome.
      It was composed of flavoprotein subunits of Mr 54,000 and cytochrome subunits of
      Mr 12,500. The midpoint redox potential of the cytochrome was 232 mV. The Km and
      kcat for p-cresol were 21 microM and 112 s-1 respectively, and the Km for
      phenazine methosulfate, the artificial acceptor used in the assays, was
      determined to be 1.7 mM. These properties place the enzyme in the same class as
      the p-cresol methylhydroxylases from aerobically isolated Pseudomonas spp.

PMID- 1991720
TI  - Mutations in the Escherichia coli dnaG gene suggest coupling between DNA
      replication and chromosome partitioning.
AB  - Eleven conditional lethal dnaG(Ts) mutations were located by chemical cleavage of
      heteroduplexes formed between polymerase chain reaction-amplified DNAs from wild
      type and mutant dnaG genes. This entailed end labeling one DNA strand of the
      heteroduplex, chemically modifying the strands with hydroxylamine or osmium
      tetroxide (OsO4) at the site of mismatch, and cleaving them with piperidine. The
      cleavage products were electrophoresed, and the size corresponded to the position
      of the mutation with respect to the labeled primer. Exact base pair changes were
      then determined by DNA sequence analysis. The dnaG3, dnaG308, and dnaG399
      mutations map within 135 nucleotides of one another near the middle of dnaG. The
      "parB" allele of dnaG is 36 bp from the 3' end of dnaG and 9 bp downstream of
      dnaG2903; both appear to result in abnormal chromosome partitioning and diffuse
      nucleoid staining. A suppressor of the dnaG2903 allele (sdgA5) maps within the
      terminator T1 just 5' to the dnaG gene. Isogenic strains that carried dnaG2903
      and did or did not carry the sdgA5 suppressor were analyzed by a combination of
      phase-contrast and fluorescence microscopy with 4',6-diamidino-2-phenylindole to
      stain DNA and visualize the partitioning chromosome. Overexpression of the mutant
      dnaG allele corrected the abnormal diffuse-nucleoid-staining phenotype associated
      with normally expressed dnaG2903. The mutations within the dnaG gene appear to
      cluster into two regions which may represent distinct functional domains within
      the primase protein.

PMID- 1991723
TI  - The nadI region of Salmonella typhimurium encodes a bifunctional regulatory
      protein.
AB  - Mutants of the nadI and pnuA genes were independently isolated on the basis of
      defects in repression of NAD biosynthetic genes and defects in transport
      nicotinamide mononucleotide (NMN). The mutations map at min 99 on the Salmonella
      chromosome, and the affected regions appear to be cotranscribed. Some pairs of
      nadI and pnuA mutations complement, suggesting the existence of independent
      functions. However, cis/trans tests with particular mutations provide evidence
      that both repressor and transport functions are actually performed by a single
      bifunctional protein. (This result confirms sequencing data of Foster and
      coworkers [J. W. Foster, Y. K. Park, T. Fenger, and M. P. Spector, J. Bacteriol.
      172:4187-4196, 1990]). We have designated the gene for this bifunctional protein
      nadI and distinguish the regulatory and transport defects with phenotypic
      designations (R and T). When a nadI(R- T+) mutation (eliminating only repression
      function) is placed cis to a superrepressor mutation, nadI(Rs T-), the
      superrepression phenotype is lost. In contrast, placement of R- and Rs T-
      mutations in trans allows full superrepression. This result suggests that the
      transport function (eliminated by the Rs T- mutation) and the repression function
      are provided by the same protein. Insertion mutations in the promoter-proximal
      repressor region of the nadI gene eliminate transport function unless the
      inserted element can provide both for both transcription and translation start
      signals; this finding suggests that there is no transcriptional or translational
      start between the regions encoding repression and transport functions.

PMID- 1991721
TI  - Integration host factor of Escherichia coli reverses the inhibition of R6K
      plasmid replication by pi initiator protein.
AB  - Integration host factor (IHF) protein is the only host-encoded protein known to
      bind and to affect replication of the gamma origin of Escherichia coli plasmid
      R6K. We examined the ability of R6K origins to replicate in cells lacking either
      of the two subunits of IHF. As shown previously, the gamma origin cannot
      replicate in IHF-deficient cells. However, this inability to replicate was
      relieved under the following conditions: underproduction of the wild-type pi
      replication protein of R6K or production of normal levels of mutant pi proteins
      which exhibit relaxed replication control. The copy number of plasmids containing
      the primary R6K origins (alpha and beta) is substantially reduced in IHF
      deficient bacteria. Furthermore, replication of these plasmids is completely
      inhibited if the IHF-deficient strains contain a helper plasmid producing
      additional wild-type pi protein. IHF protein has previously been shown to bind to
      two sites within the gamma origin. These sites flank a central repeat segment
      which binds pi protein. We propose a model in which IHF binding to its sites
      reduces the replication inhibitor activity of pi protein at all three R6K
      origins.

PMID- 1991724
TI  - Activity of the nicotinamide mononucleotide transport system is regulated in
      Salmonella typhimurium.
AB  - Transport of nicotinamide mononucleotide (NMN) requires two functions, NadI(T)
      and PnuC. The PnuC protein is membrane associated, as judged by isolation of
      active TnphoA gene fusions and demonstration that the fusion protein is membrane
      associated. The PnuC function appears to be the major component of the transport
      system, since mutant alleles of the pnuC gene permit NMN transport in the absence
      of NadI(T) function. We present evidence that the activity of the NMN transport
      system varies in response to internal pyridine levels (presumably NAD). This
      control mechanism requires NadI(T) function, which is provided by a bifunctional
      protein encoded by the nadI gene (called nadR by Foster and co-workers [J. W.
      Foster, Y. K. Park, T. Fenger, and M. P. Spector, J. Bacteriol. 172:4187-4196]).
      The nadI protein regulates transcription of the nadA and nadB biosynthetic genes
      and modulates activity of the NMN permease; both regulatory activities respond to
      the internal pyridine nucleotide level.

PMID- 1991726
TI  - Map position and genomic organization of the kps cluster for polysialic acid
      synthesis in Escherichia coli K1.
AB  - The multigenic kps cluster in Escherichia coli K1 encodes functions for synthesis
      of a polysialic acid capsule. DNA probes flanking each side of the cluster were
      hybridized to lambda clones bearing overlapping E. coli W3110 genomic fragments.
      These fragments covered the region between 60 and 70 map units on the chromosome.
      The results located kps to an accretion domain near 64 map units and established
      the orientation of kps cluster genes. Acquisition of kps by the E. coli genome
      was apparently the result of an ancestral transpositionlike addition event.

PMID- 1991725
TI  - Facultative alkaliphiles lack fatty acid desaturase activity and lose the ability
      to grow at near-neutral pH when supplemented with an unsaturated fatty acid.
AB  - Two obligate alkaliphiles were found to have high levels of fatty acid
      desaturase, whereas two facultative alkaliphiles had no detectable activity.
      Supplementation of the growth medium of one facultative strain with palmitoleic
      acid, but not palmitic acid, at pH 7.5 inhibited growth. The obligate strain
      outgrows the facultative strain in a chemostat at a very high pH, whereas the
      converse is true at a pH of 7.5, and the two strains grow equally well at pH 9.0.
      Thus, the obligate strain is compromised at a near-neutral pH but is better
      adapted than a related facultative alkaliphile to an extremely alkaline pH.

PMID- 1991727
TI  - High-frequency rearrangements in Rhizobium leguminosarum bv. phaseoli plasmids.
AB  - High-frequency genomic rearrangements affecting the plasmids of Rhizobium
      leguminosarum bv. phaseoli CFN42 were analyzed. This strain contains six large
      plasmids ranging in size from 200 to 600 kb. In the absence of any selective
      pressure, we found 11 strains from 320 analyzed colonies that presented different
      kinds of plasmid-borne rearrangements, including sequence amplification,
      deletion, cointegration, and loss of plasmids. These data support the concept
      that the R. leguminosarum bv. phaseoli genome is a dynamic structure and imply
      that strains are mixtures of similar but not identical cells.

PMID- 1991728
TI  - Efficient transformation of Bacillus thuringiensis requires nonmethylated plasmid
      DNA.
AB  - The transformation efficiency of Bacillus thuringiensis depends upon the source
      of plasmid DNA. DNA isolated from B. thuringiensis, Bacillus megaterium, or a Dam
      Dcm- Escherichia coli strain efficiently transformed several B. thuringiensis
      strains, B. thuringiensis strains were grouped according to which B.
      thuringiensis backgrounds were suitable sources of DNA for transformation of
      other B. thuringiensis strains, suggesting that B. thuringiensis strains differ
      in DNA modification and restriction. Efficient transformation allowed the
      demonstration of developmental regulation of cloned crystal protein genes in B.
      thuringiensis.

PMID- 1991729
TI  - N-terminal amino acid sequences and amino acid compositions of the Spirochaeta
      aurantia flagellar filament polypeptides.
AB  - The amino-terminal sequences and amino acid compositions of the three major and
      two minor polypeptides constituting the filaments of Spirochaeta aurantia
      periplasmic flagella were determined. The amino-terminal sequence of the major
      37.5-kDa outer layer polypeptide is identical to the sequence downstream of the
      proposed signal peptide of the protein encoded by the S. aurantia flaA gene.
      However, the amino acid composition of the 37.5-kDa polypeptide is not in
      agreement with that inferred from the sequence of flaA. The 34- and 31.5-kDa
      major filament core polypeptides and the 33- and 32-kDa minor core polypeptides
      show a striking similarity to each other, and the amino-terminal sequences of
      these core polypeptides show extensive identity with homologous proteins from
      members of other genera of spirochetes. An additional 36-kDa minor polypeptide
      that occurs occasionally in preparations of S. aurantia periplasmic flagella
      appears to be mixed with the 37.5-kDa outer layer polypeptide or a degradation
      product of this polypeptide.

PMID- 1991730
TI  - Suppression of the defects in rdgB mutants of Escherichia coli K-12 by the cloned
      purA gene.
AB  - A gene suppressing the defects of Escherichia coli rdgB (recA-dependent growth)
      and recA(Ts) rdgB mutants was cloned. The cloned gene suppresses the hyper-Rec
      phenotype and the enhanced level of SOS functions in rdgB mutants at the
      nonpermissive temperature. We identified the cloned gene as purA.

PMID- 1991731
TI  - Cloning and comparison of the DNA encoding ammelide aminohydrolase and cyanuric
      acid amidohydrolase from three s-triazine-degrading bacterial strains.
AB  - DNA encoding the catabolism of the s-triazines ammelide and cyanuric acid was
      cloned from Pseudomonas sp. strain NRRLB-12228 and Klebsiella pneumoniae 99 with,
      as a probe, a 4.6-kb PstI fragment from a third strain, Pseudomonas sp. strain
      NRRLB-12227, which also encodes these activities. In strains NRRLB-12228 and 99
      the ammelide aminohydrolase (trzC) and cyanuric acid amidohydrolase (trzD) genes
      are located on identical 4.6-kb PstI fragments which are part of a 12.4-kb DNA
      segment present in both strains. Strain NRRLB-12227 also carries this 12.4-kb DNA
      segment, except that a DNA segment of 0.8 to 1.85 kb encoding a third enzyme,
      ammeline aminohydrolase (trzB), has been inserted next to the ammelide
      aminohydrolase gene with the accompanying deletion of 1.1 to 2.15 kb of DNA. In
      addition, the s-triazine catabolic genes are flanked in strain NRRLB-12227 by
      apparently identical 2.2-kb segments that are not present in the other two
      strains and that seem to cause rearrangements in adjacent DNA.

PMID- 1991732
TI  - Defective transcription of the right end of bacteriophage T7 DNA during an
      abortive infection of F plasmid-containing Escherichia coli.
AB  - Transcription of T7 and mutant T3 DNA during infections of F plasmid-containing
      cells has been analyzed by using Southern hybridization. A transcriptional defect
      is apparent in these abortively infected cells that is most severe in the class
      III region of the phage genome. In particular, RNAs that are initiated from the
      gene 13 promoter are not elongated to give full-length molecules. It is suggested
      that the transcription defect results from positive supercoiling of the template
      DNA and that torsional constraints may even prevent the complete entry of the
      phage genome into an abortively infected cell.

PMID- 1991733
TI  - Halobacterium halobium strains lysogenic for phage phi H contain a protein
      resembling coliphage repressors.
AB  - DNA-binding proteins such as bacteriophage repressors belong to the helix-turn
      helix family. Ionic interactions drive DNA binding, which means that repressors
      bind DNA most tightly at low salt concentrations. This raises the question of who
      gene expression might be regulated in obligate halophiles, which maintain
      internal salt concentrations of about 5 M. As a model system we have investigated
      the phage phi H, which infects the archaebacterium Halobacterium halobium.
      Previous genetic data and transcriptional mapping had suggested a region of the
      phage genome where a repressor might bind. A modified electrophoretic mobility
      shift assay was used to identify an activity, present only in lysogens, that
      specifically binds this region. Methylation interference and DNA sequencing were
      used to identify four similar binding sites, which are arranged so that two
      copies of a dimer might bind on one face of the DNA helix. Binding of a protein
      at these sites could block RNA polymerase from initiating a transcript found only
      during lytic growth. A nearby divergent promoter produces a lysogen-specific
      transcript, T6, which encodes a member of the helix-turn-helix family of DNA
      binding proteins. By expressing the gene in Escherichia coli, we confirmed that
      T6 specifies the DNA binding activity detected biochemically. The data show that
      the basic DNA-binding motif of repressors can be adapted even for the unfavorable
      conditions of high salt concentration.

PMID- 1991734
TI  - Immunocytochemical localization of the coenzyme F420-reducing hydrogenase in
      Methanosarcina barkeri Fusaro.
AB  - The cytological localization of the 8-hydroxy-5-deazaflavin (coenzyme F420)
      reducing hydrogenase of Methanosarcina barkeri Fusaro was determined by
      immunoelectron microscopy, using a specific polyclonal rabbit antiserum raised
      against the homogeneous deazaflavin-dependent enzyme. In Western blot
      (immunoblot) experiments this antiserum reacted specifically with the native
      coenzyme F420-reducing hydrogenase, but did not cross-react with the coenzyme
      F420-nonreducing hydrogenase activity also detectable in crude extracts prepared
      from methanol-grown Methanosarcina cells. Immunogold labelling of ultrathin
      sections of anaerobically fixed methanol-grown cells from the exponential growth
      phase revealed that the coenzyme F420-reducing hydrogenase was predominantly
      located in the vicinity of the cytoplasmic membrane. From this result we
      concluded that the deazaflavin-dependent hydrogenase is associated with the
      cytoplasmic membrane in intact cells of M. barkeri during growth on methanol as
      the sole methanogenic substrate, and a possible role of this enzyme in the
      generation of the electrochemical proton gradient is discussed.

PMID- 1991735
TI  - Cloning and location of a gene governing lysine epsilon-aminotransferase, an
      enzyme initiating beta-lactam biosynthesis in Streptomyces spp.
AB  - In actinomycetes that produce beta-lactam antibiotics of the cephem type, lysine
      epsilon-aminotransferase is the initial enzyme in the conversion of lysine to
      alpha-aminoadipic acid. We used a two-stage process ("chromosome walking") to
      screen a lambda library of Streptomyces clavuligerus genomic DNA for fragments
      that expressed lysine epsilon-aminotransferase activity in S. lividans.
      Restriction analysis of the cloned DNA confirmed the location of the putative lat
      gene within the cluster of beta-lactam biosynthesis genes, roughly midway between
      pcbC, the structural gene for isopenicillin N synthetase, and the putative cefE
      gene encoding deacetoxycephalosporin C synthetase.

PMID- 1991736
TI  - Velocity changes, long runs, and reversals in the Chromatium minus swimming
      response.
AB  - The velocity, run time, path curvature, and reorientation angle of Chromatium
      minus were measured as a function of light intensity, temperature, viscosity,
      osmotic pressure, and hydrogen sulfide concentration. C. minus changed both
      velocity and run time. Velocity decreased with increasing light intensity in
      sulfide-depleted cultures and increased in sulfide-replete cultures. The addition
      of sulfide to cultures grown at low light intensity (10 microeinsteins m-2 s-1)
      caused mean run times to increase from 10.5 to 20.6 s. The addition of sulfide to
      cultures grown at high light intensity (100 microeinsteins m-2 s-1) caused mean
      run times to decrease from 15.3 to 7.7 s. These changes were maintained for up to
      an hour and indicate that at least some members of the family Chromatiaceae
      simultaneously modulate velocity and turning frequency for extended periods as
      part of normal taxis.

PMID- 1991737
TI  - Podiatry.

PMID- 1991738
TI  - Brucellar and tuberculous spondylitis. A comparative study of their clinical
      features.
AB  - The clinical data from 19 patients with brucellar spondylitis and 15 with
      tuberculous spondylitis were compared. The former disease affects males whose
      occupations expose them to Brucella. The lumbar spine is usually involved and
      there are other symptoms of brucellosis. Tuberculous spondylitis is not usually
      accompanied by general symptoms. The dorsal spine is more frequently affected and
      may exhibit vertebral collapse and paraspinal abscesses. These differences permit
      a presumptive aetiological diagnosis, but the definitive diagnosis depends upon
      bacteriological tests.

PMID- 1991739
TI  - Spinal instability secondary to metastatic cancer.
AB  - Fifty-five patients with severe pain from spinal instability secondary to
      metastatic cancer were referred to Hope Hospital, none being judged to be in a
      terminal condition. One patient had too extensive disease for surgery so 54 were
      treated by 55 spinal stabilisations; 49 obtained complete relief of pain and two
      had partial relief. There were three failures. Twenty-eight of the patients had
      clinical evidence of spinal cord or cauda equina compression and were
      decompressed at the time of stabilisation. Of these, 20 had major recovery of
      neurological function. Patients with pre-operative evidence of extradural tumour
      had 'prophylactic' decompression at the time of stabilisation; none of these
      patients later developed signs of cord or cauda equina compression. The results
      suggest that alleviation of pain and restoration of mobility are best achieved by
      segmental spinal stabilisation; a few patients require a combined anterior and
      posterior stabilisation. Postoperative radiotherapy should be given whenever
      possible, and the causative tumour should be treated by endocrine or
      chemotherapy, as indicated.

PMID- 1991740
TI  - Intraosseous lipomatosis. A case report.
AB  - We report a case of systemic intraosseous lipomatosis involving the proximal
      femur, both ends of the tibia, and the tarsal and metatarsal bones. The lesions
      progressed during a five-year follow-up with a pathological fracture of the
      tibial plateau. CT scans were characteristic and helpful in diagnosis but MR
      imaging added little information. Intraosseous lipomatosis is a hamartomatous
      malformation due to hyperplasia of adipose tissue, and is fundamentally different
      from solitary benign intraosseous lipoma. Management involves reconstruction of
      any pathological fracture. Large progressive lesions should be treated by
      curettage and grafting in an attempt to prevent such fractures.

PMID- 1991741
TI  - Dislocation after primary arthroplasty for subcapital fracture of the hip. Wide
      range of movement is a risk factor.
AB  - Dislocation is the most frequent serious complication following total hip
      replacement for subcapital femoral fracture. We report a prospective study, using
      matched groups, which compared the range of hip movement following hip
      replacement for arthritis and for fracture. The range of movement was
      significantly greater in the fracture group. We suggest that this is a
      predisposing factor for dislocation.

PMID- 1991742
TI  - Noise-induced hearing loss in orthopaedic staff.
AB  - In the light of EEC proposals on the avoidance of damage to hearing caused by
      noise, a study was undertaken to determine the risk posed by powered orthopaedic
      instruments. The noise levels from a number of air-powered and electric tools
      were measured and analysed and found to exceed the recommended levels. The
      predicted daily personal noise exposure was calculated and the potential for
      hearing damage confirmed. Twenty-seven senior orthopaedic staff were then
      assessed by audiometry; evidence of noise-induced hearing loss was found in half
      the subjects. The increasing use of powered instruments in elective orthopaedics
      and fracture fixation may present a significant cumulative risk to the hearing of
      orthopaedic surgeons and theatre personnel. The use of ear defenders should be
      promoted, and manufacturers should be encouraged to develop instruments with
      lower noise emission levels.

PMID- 1991743
TI  - Ten-year results of operations for rheumatoid cervical spine disorders.
AB  - The outcome of operations performed on 38 patients for rheumatoid disorders of
      the cervical spine were analysed 10 or more years later. The mean age of the
      patients at the time of operation was 56 years (35 to 77); 32 had seropositive
      disease. The mean duration of the disease was 17 years (four to 36). Twenty-seven
      patients had painful anterior atlanto-axial subluxation (AAS), nine had subaxial
      subluxation alone and two had severe cranial subluxation of the odontoid, one
      also with subaxial subluxation. One patient died from postoperative
      staphylococcal septicaemia and another 18 died during the follow-up period.
      Patients with coincident cardiac or other diseases, and those with cranial
      subluxation of the odontoid of more than 3 mm had an increased mortality. Neither
      the patients' age nor the magnitude of AAS correlated with mortality. Of the 37
      patients with occipitocervical pain, 30 were relieved and all the six patients
      with tetraparesis were improved. Of the 24 Gallie fusions only 12 were solidly
      united; patients with long-term cortisone treatment were more likely to develop
      pseudarthrosis. There was no correlation between clinical outcome and
      radiological result. Four patients had further operations to treat subluxation
      which developed below the fused segments.

PMID- 1991744
TI  - Surgical treatment of double major scoliosis. Improvement of the lumbar curve
      after fusion of the thoracic curve.
AB  - We have evaluated two methods of surgical treatment of adolescent idiopathic
      double major scoliosis in 59 patients. In group 1, 31 patients were treated by
      fusion of the upper curve only. In group 2, 28 patients had lumbar fusions also
      including most of the lower curve. The magnitude of the lower curve and the
      correction obtained in traction were good indicators of the correction achieved
      postoperatively. Forty-four patients were reviewed at a minimum of 10 years after
      operation. Those in group 1 showed sustained improvement of the lower curve with
      minimal stiffness and pain. Group 2 patients had lumbar curves of similar
      severity at review, but had significantly more low back pain and stiffness. The
      number of lumbar segments which remained mobile appeared to be a critical factor
      in determining the outcome. Selective fusion of the upper curve in double major
      scoliosis produces satisfactory results if the lumbar curve is less than 50
      degrees. It may also be appropriate for flexible lumbar curves of larger angle.

PMID- 1991745
TI  - Tarsal tunnel syndrome. Causes and results of operative treatment.
AB  - From 1975 to 1988, operative treatment was performed on 50 feet in 45 patients
      with tarsal tunnel syndrome. The causes of this syndrome were correlated with
      operative findings and included ganglia in 18, and a bony prominence from
      talocalcaneal coalition in 15. Five feet had sustained an injury, tumours were
      found in three and there was no obvious cause in nine. In most cases in need of
      operative treatment, there was a space-occupying lesion. Classifying the results
      according to causes, those with coalition or a tumour fared better, and
      idiopathic and traumatic cases had a worse outcome. In cases with a definite
      lesion, an excellent result can be expected from surgical treatment carried out
      soon after onset of the condition.

PMID- 1991746
TI  - Treatment of Freiberg's disease. A new operative technique.
AB  - A method of treating Freiberg's disease of the metatarsal head by shortening the
      metatarsal bone is described. This operation has been performed in 15 patients
      (16 feet). Excellent relief of pain was obtained, although most patients had
      persistent stiffness of the metatarsophalangeal joint.

PMID- 1991747
TI  - On the problem of heat generation in bone cutting. Studies on the effects on
      liquid cooling.
AB  - A saw blade was made from two standard oscillating blades which were fixed to
      each other with channels between, so that cooling fluid could be directed to the
      saw teeth. The blade was connected to a standard arthroscopy pump which delivered
      a flow of 80 ml/min through the blade. The performance of this blade was compared
      with that of a standard saw blade, cutting ox-bone in the laboratory. Irrigation
      of the standard saw blade with saline delivered by a syringe only slightly
      diminished the maximum temperature. Pumped irrigation was more effective but
      required large volumes of fluid. The heat generated by the internally cooled saw
      blade was negligible and the temperatures achieved (19 degrees C to 34 degrees C)
      fell well below the critical level for bone death (44 degrees C to 47 degrees C).

PMID- 1991748
TI  - The surgical treatment of ingrowing toenails.
AB  - Two prospective studies of ingrowing toenail management were conducted. In the
      first, 163 patients (204 ingrowing nail edges) who had not had previous surgery
      were randomised and treated by total nail avulsion, nail edge excision, or nail
      edge excision with phenolisation of the germinal matrix; recurrence rates one
      year postoperatively were 73%, 73% and 9% respectively. In the second study, 63
      ingrowing nail edges which had recurred after previous operations underwent nail
      edge excision and phenolisation. There was a 5% recurrence rate and 5% incidence
      of dystrophy of the nail one year after operation.

PMID- 1991749
TI  - Scaphoid malunion.
AB  - We reviewed 10 patients with symptomatic malunion of a carpal scaphoid fracture.
      All had displacement with dorsiflexed intercalated segment instability, and
      suffered from pain, restricted range of movement at the wrist and decreased grip
      strength. The restriction of flexion-extension and the decreased grip strength
      correlated with the severity of the DISI deformity. Seven patients had a
      corrective osteotomy, using an anterior wedge-shape bone graft with internal
      fixation by Herbert screw, and all had satisfactory results. We believe that
      symptoms associated with scaphoid malunion are related to consequent carpal
      deformity.

PMID- 1991750
TI  - Fracture-separation of the distal humeral epiphysis.
AB  - We have reviewed 12 cases of fracture-separation of the distal humeral epiphysis,
      three of which were initially misdiagnosed as fractures of the lateral condyle
      and one as an elbow dislocation. Cubitus varus deformity is as common after this
      fracture-separation as it is following supracondylar fracture, and is most common
      in children under two years of age. Closed reduction and simple immobilisation is
      adequate for the older child, but we recommend for those under two years of age
      that closed reduction should be followed by percutaneous pinning, so that the
      carrying angle can be assessed immediately after reduction. If the elbow is then
      in varus the wires should be removed, reduction repeated and treatment by
      straight lateral traction used to maintain a valgus carrying angle.

PMID- 1991751
TI  - Transarticular fixation for severely displaced supracondylar fractures in
      children.
AB  - We have reviewed 34 children who had been treated by open reduction through a
      medial incision and transarticular pinning for a severely displaced supracondylar
      fracture of the humerus. Follow-up ranging from nine months to 20 years showed
      that 27 of 34 elbows (79%) had excellent or good results, with satisfactory
      resolution of neurovascular problems and no complications due to the method of
      treatment.

PMID- 1991752
TI  - The coracohumeral ligament. Anatomy of a substantial but neglected structure.
AB  - We dissected 60 shoulders to demonstrate the anatomy of the coracohumeral
      ligament. The role of this structure in clinical problems of the shoulder is
      discussed.

PMID- 1991753
TI  - Repair of median and ulnar nerves. Primary suture is best.
AB  - We reviewed, at two to seven years, the results of repair of 108 median and ulnar
      nerves after clean transection injury between the elbow and wrist in 95 patients
      ranging in age from 15 to 55 years. Of these, 48 nerves had primary suture, 25
      had delayed suture, and 35 were grafted, all repairs being performed by the
      senior author using standard techniques. Assessment was based on the methods and
      grading described by Seddon (1975). Thirteen of 60 secondary repairs or grafts
      failed, but no primary repair failed completely. There were few excellent
      results; they were found only after primary distal repair in younger patients.

PMID- 1991754
TI  - Bone lesions secondary to benign phaeochromocytoma. Four cases in childhood.
AB  - Metaphyseal sclerotic bone changes associated with benign phaeochromocytoma are
      very rare in childhood. We report four cases, in each of which the radiographic
      changes returned to normal after removal of the tumour.

PMID- 1991755
TI  - Internal fixation of femoral neck fractures. Two methods compared.
AB  - In a prospective randomised study, the Hansson pin technique for internal
      fixation of fractures of the femoral neck was compared with the Uppsala screw
      technique. The series consisted of 115 consecutive patients, 97 women and 18 men,
      with a mean age of 80 years. There were 56 patients treated with Hansson pins and
      59 with Uppsala screws. After one year 22 patients had died, eight in the Hansson
      pin group and 14 in the Uppsala screw group (p = 0.28). Twenty-four complications
      had occurred, 18 in the Hansson pin group and six in the Uppsala screw group (p =
      0.008). After exclusion of those with complications, the patients in the Hansson
      pin group had significantly more pain, less mobility, and a smaller proportion
      were living in their own homes.

PMID- 1991756
TI  - Chondrosarcoma of the soft tissues. Two different sub-groups.
AB  - Chondrosarcomas arising from soft tissues are rare. Two different varieties are
      described, myxoid and mesenchymal. We have collected nine cases of the tumour,
      five myxoid and four mesenchymal, from a review of 513 cases of chondrosarcoma
      seen between 1904 and 1988. We report the principal clinical, radiographical and
      histological differences between the two varieties and discuss their surgical
      treatment and prognosis.

PMID- 1991757
TI  - Anterior trochanteric muscle pedicle graft.

PMID- 1991759
TI  - Percutaneous epiphysiodesis.

PMID- 1991758
TI  - Brachial plexus palsy after manipulation of the shoulder.

PMID- 1991760
TI  - Hypercalcaemia and nephrolithiasis following multiple fractures.

PMID- 1991761
TI  - Ultrasound in the detection of subperiosteal abscesses.

PMID- 1991762
TI  - Combined basal metacarpal fracture and ligament injury of the metacarpophalangeal
      joint of the thumb.

PMID- 1991763
TI  - Wheelguards: a safety measure in the operating room.

PMID- 1991764
TI  - Chronic compartment syndrome of both feet.

PMID- 1991766
TI  - Shoulder arthrodesis using an external fixator.

PMID- 1991765
TI  - A quick method of taking a bone graft.

PMID- 1991767
TI  - Fatigue failure of noncemented porous-coated implants. A retrieval study.
AB  - The causes of mechanical failure of five noncemented porous-coated components
      were studied. There were two cobalt-chromium alloy and three titanium alloy
      implants which fractured after 12 to 48 months. The implants included one
      acetabular component, and one femoral condylar, one patellar and two tibial
      components. Examination of the fractured surfaces revealed fatigue to be the
      mechanism of failure in all cases. The porous coating and the processes required
      for its fabrication had resulted in weakening and reduction of substrate
      thickness. Additional factors were stress concentration due to limited, localised
      bone ingrowth, and some features of the design of the implants.

PMID- 1991768
TI  - Sensitivity to titanium. A cause of implant failure?
AB  - Tissues from five patients who underwent revision operations for failed total hip
      replacements were found to contain large quantities of particulate titanium. In
      four cases this metal must have come from titanium alloy screws used to fix the
      acetabular component; in the fifth case it may also have originated from a
      titanium alloy femoral head. Monoclonal antibody labelling showed abundant
      macrophages and T-lymphocytes, in the absence of B-lymphocytes, suggesting
      sensitisation to titanium. Skin patch testing with dilute solutions of titanium
      salts gave negative results in all five patients. However, two of them had a
      positive skin test to a titanium-containing ointment.

PMID- 1991769
TI  - Pseudo-abscess of the psoas bursa in failed double-cup arthroplasty of the hip.
AB  - Seven psoas bursae filled with purulent fluid and inspissated debris were
      revealed at revision operations for failed resurfacing hip arthroplasties, an
      incidence of 5.8% in such revisions. Histological and microbiological
      investigations demonstrated that the psoas bursa collections resulted from the
      tissue response to polyethylene wear debris. None was due to infection.

PMID- 1991770
TI  - Correction of coxa vara in childhood. The use of Pauwels' Y-shaped osteotomy.
AB  - The long-term results following the correction of coxa vara by Pauwels' Y-shaped
      intertrochanteric osteotomy have been evaluated in 14 children. Ten of the
      children had unilateral hip disease and were otherwise normal while four had
      bilateral hip disease due to generalised skeletal dysplasias. In each case, the
      growth plate was vertical, the femoral head was displaced inferiorly and there
      were abnormalities in the metaphysis of the femoral neck. The results indicate
      that this osteotomy provides lasting correction of the deformity, regardless of
      the cause, as long as the inclination of the growth plate is corrected to 40
      degrees or less and adequate support is provided for the metaphyseal defect and
      the displaced femoral head.

PMID- 1991771
TI  - Micromotion of cemented and uncemented femoral components.
AB  - We evaluated the initial stability of cemented and uncemented femoral components
      within the femoral canals of cadaver femurs during simulated single limb stance
      and stair climbing. Both types were very stable in simulated single limb stance
      (maximum micromotion of 42 microns for cemented and 30 microns for uncemented
      components). However, in simulated stair climbing, the cemented components were
      much more stable than the uncemented components (76 microns as against 280
      microns). There was also greater variation in the stability of uncemented
      components in simulated stair climbing, with two of the seven components moving
      200 microns or more. Future implant designs should aim to improve the initial
      stability of cementless femoral components under torsional loads; this should
      improve the chances of bony ingrowth.

PMID- 1991772
TI  - Immunopathological response to loose cementless acetabular components.
AB  - The membranes surrounding seven loose cementless acetabular implants were shown
      to contain polyethylene particles, birefringent in polarised light. Three of
      these implants were made of titanium alloy and the membranes around these
      contained titanium particles as well. There was no metallosis around the four
      implants made of chromium-cobalt-steel alloy. Both titanium and polyethylene
      particles caused migration, adherence and phagocytosis of CD11b-positive,
      peroxidase-negative macrophages. There were no histological signs of activation
      of the specific immune response; neither interleukin-2 receptor-positive
      activated T cells nor PCA-1 plasmablasts/plasma cells were present in the
      tissues. In cases of simple loosening, resident mesenchymal fibroblast-like cells
      were active. In aggressive granulomatosis, there were many macrophages and
      multinucleated giant cells but little fibroblast reaction. The clinical relevance
      of the findings is that the use of cementless prostheses is not a guarantee
      against adverse tissue reactions.

PMID- 1991773
TI  - Effect of stem modulus in a total hip arthroplasty model.
AB  - The purpose of this study was to determine the biological effects of the elastic
      modulus of the femoral stem in canine hip arthroplasty. Cementless total hip
      arthroplasty was performed in 12 dogs, six had a low elastic modulus polyacetal
      resin stem and six had a high modulus stainless steel stem. The components were
      otherwise similar. At six and 12 months after operation, radiographic and
      histomorphometric analysis showed that those with steel implants had more
      cortical porosity than did the other group (p less than 0.01). We suggest that
      the elastic modulus of the implant is an important factor in controlling cortical
      bone resorption. A low modulus femoral prosthesis can significantly decrease bone
      resorption which might otherwise eventually lead to implant failure.

PMID- 1991774
TI  - The effect of continuous passive motion on knee ligament reconstruction with
      carbon fibre. An experimental investigation.
AB  - Our purpose was to determine whether continuous passive motion enhanced the
      quality of knee ligament reconstruction using carbon fibre. In 46 rabbits the
      medial collateral ligaments were excised and replaced with carbon fibre
      prostheses. The animals were treated postoperatively by either continuous passive
      motion, cast immobilisation or cage activity, termed intermittent active motion.
      At six weeks, the ligaments were compared histologically and biomechanically with
      normal (control) medial collateral ligaments and with sham-operated controls. The
      ligaments treated with continuous passive motion were superior to those in the
      other two treatment groups. There were no ligament failures in any of the groups.
      This study suggests that continuous passive motion, initiated immediately
      postoperatively, enhances the biomechanical properties of carbon fibre ligament
      replacement of the medial collateral ligament while preventing the harmful
      effects of joint immobilisation.

PMID- 1991775
TI  - Joint proprioception in normal, osteoarthritic and replaced knees.
AB  - We measured joint position sense in the knee by a new method which tests the
      proprioceptive contribution of the joint capsule and ligaments. The leg was
      supported on a splint, and held in several positions of flexion. The subjects'
      perception of the position was recorded on a visual analogue model and compared
      with the actual angle of flexion. Eighty-one normal and 45 osteoarthritic knees
      were examined, as were 10 knees with semi-constrained and 11 with hinged joint
      replacements. All were assessed with and without an elastic bandage around the
      knee. There was a steady decline in joint position sense with age in subjects
      with normal knees. Those with osteoarthritic knees had impaired joint position
      sense at all ages (p less than 0.001). Knee replacement improved the joint
      position sense slightly (p less than 0.02); semi-constrained replacement had a
      greater effect than hinged replacement. The effect of an elastic bandage in
      subjects with poor position sense was dramatic, improving accuracy by 40% (p less
      than 0.001). It is proposed that reduced proprioception in elderly and
      osteoarthritic subjects may be responsible for initiation or advancement of
      degeneration of the knee.

PMID- 1991776
TI  - Repair of cartilage lesions using biological implants. A comparative histological
      and biomechanical study in goats.
AB  - We report the experimental use of three different biological implants to restore
      articular surface defects: glutaraldehyde-fixed bovine meniscal xenograft,
      glutaraldehyde-fixed bovine costal cartilage xenograft, and viable osteochondral
      allografts. The grafts were implanted in the knees of 19 goats who were allowed
      free-field activity and were studied for up to one year. The natural articular
      surfaces of meniscal fibrocartilage provided excellent articular surfaces at all
      times. Equally good articular surfaces were restored by host tissue growth
      covering costal cartilage grafts at six months, but by 12 months this surface had
      degenerated. The majority of the allografts survived and integrated with the host
      at six months, but many showed signs of failure at 12 months. Only three out of
      seven ungrafted defects healed completely at six months and the healed surfaces
      were degenerating at 12 months.

PMID- 1991777
TI  - Bone structure after removal of internal fixation plates.
AB  - We used single-photon absorptiometry to assess the forearm bones after the
      removal of internal fixation plates in 14 patients. We found convincing evidence
      of cortical atrophy in only one patient, in whom the plates had been removed
      prematurely after only 16 months. It is suggested that such plates should be
      retained for at least 21 months, to allow bone density to return to its
      prefracture level. The recommendations of the AO/ASIF group are supported.

PMID- 1991778
TI  - Natural history of nontraumatic avascular necrosis of the femoral head.
AB  - We studied the natural history of nontraumatic avascular necrosis of the femoral
      head (ANFH) in 115 hips in 87 patients, 69 steroid-induced, 21 related to misuse
      of alcohol and 25 idiopathic. The average length of follow-up was over five
      years. Collapse occurred most often when the focus of bone necrosis occupied the
      weight-bearing surface of the femoral head. Flatness of the head due to
      subchondral fracture was an early manifestation of collapse. Classification into
      six types based upon the radiographic findings provided an accurate prognosis for
      individual cases of ANFH which is useful in planning treatment and in assessing
      its outcome.

PMID- 1991779
TI  - Failure of internal fixation of displaced femoral neck fractures in rheumatoid
      patients.
AB  - We reviewed the records and radiographs from 10 hospitals to identify 50 patients
      with rheumatoid arthritis (RA) who had sustained 52 femoral neck fractures. Most
      patients were female (88%), elderly (mean age 66 years) and had had severe
      polyarticular disease for a mean duration of 16 years. Over half had taken
      systemic corticosteroids, nearly all were severely osteopenic but few had
      rheumatoid changes in the hip. Of the 20 fractures treated by internal fixation
      12 had complications including nonunion (5), osteonecrosis (5), infection (1),
      and intertrochanteric fracture (1). Only one of the nine undisplaced fractures
      required reoperation, but seven of the 11 displaced fractures had revision
      surgery. Twenty fractures were treated by primary total hip arthroplasty with
      only one early complication. The other 12 fractures had been treated by
      hemiarthroplasty (9), hip excision (1) or non-operatively (2). Our results
      suggest that, in elderly rheumatoid patients, severely displaced femoral neck
      fractures should be treated by total hip replacement.

PMID- 1991780
TI  - Femoral head blood flow in femoral neck fractures. An analysis using intra
      osseous pressure measurement.
AB  - We studied 50 patients with fractures of the femoral neck, 33 intracapsular and
      17 extracapsular. Intraosseous pressure was measured by a transducer within the
      bone to quantify blood flow, and intracapsular pressure by a needle introduced
      into the joint space. The mean intracapsular pressure was lower in the
      extracapsular fractures. In these, the mean intraosseous pressure in the femoral
      head was unchanged by aspiration of the joint. However in the intracapsular
      fractures aspiration produced a significant decrease in intra-osseous pressure
      and an increase in pulse pressure within the femoral head. The results suggest
      that aspiration of intracapsular haematoma produced an increase in femoral head
      blood flow by relieving tamponade.

PMID- 1991781
TI  - A plaster-pylon technique for below-knee amputation.
AB  - We reviewed 83 patients after below-knee amputation. In 56 with 69 amputations
      early management was by plaster-pylon. A plaster cast is applied in the operating
      room, and a pylon added one week later, after which full weight-bearing is
      allowed. We compared these patients with 27 who had soft bandaging. The 'healing'
      time was reduced from 98 days to 40 days, and there were no major complications
      in the plaster-pylon group. The technique is simple and cheap and can be used by
      paramedical staff without specialised training or equipment.

PMID- 1991782
TI  - Early complications in the operative treatment of ankle fractures. Influence of
      delay before operation.
AB  - We have reviewed the early complications of 121 surgically treated closed ankle
      fractures; the complication rate was 30%, with 14 major and 22 minor
      complications. Fractures with skin blisters or abrasions had more than double the
      overall complication rate. Fracture-dislocations had three times as many major
      complications as simple fractures, and those not fixed within 24 hours had a 44%
      major complication rate compared to 5.3% in those operated upon as emergencies.
      Patients transferred from another medical facility had high complication rates,
      especially if they had fracture-dislocations. We conclude that operative
      treatment of ankle fractures must be delivered in a timely fashion, especially in
      severe fractures. We would caution against the practice of transferring patients
      with serious ankle fractures before completion of definitive care.

PMID- 1991783
TI  - Conservative management or closed nailing for tibial shaft fractures. A
      randomised prospective trial.
AB  - We performed a prospective randomised trial on matched groups of patients with
      displaced tibial shaft fractures to compare conservative treatment with closed
      intramedullary nailing. The results showed conclusively that intramedullary
      nailing gave more rapid union with less malunion and shortening. Nailed patients
      had less time off work with a more predictable and rapid return to full function.
      We therefore consider that closed intramedullary nailing is the most efficient
      treatment for displaced fractures of the tibial shaft.

PMID- 1991784
TI  - The use of a tourniquet when plating tibial fractures.
AB  - Sixty closed fractures of the tibia were treated by open reduction and internal
      fixation with plates and screws. Half the operations were performed with a thigh
      tourniquet and half without. In the tourniquet group, there were six cases with
      erythema and induration of the wound; in the other group there were no such
      complications. Despite negative bacterial cultures, superficial infection of the
      inflamed wounds was suspected. It is suggested that a tourniquet may predispose
      tissues to infection, and its use is not recommended during operations for
      internal fixation of the tibia.

PMID- 1991785
TI  - Modern splinting bandages.
AB  - We have assessed the current range of synthetic splinting bandages, using
      physical and mechanical tests and the subjective opinions of patients, volunteers
      and orthopaedic staff. Modern bandages have some better properties than standard
      plaster bandage but do not conform as well, are more expensive, and potentially
      more hazardous.

PMID- 1991786
TI  - Biomechanical effects of rockers on walking in a plaster cast.
AB  - Rockers are applied to lower limb casts to assist walking but there is little
      information on their biomechanical effects. The performances of 10 commercially
      available rockers were compared. They were applied to a below-knee cast worn by a
      normal subject who was also tested walking in the cast alone. Gait analysis was
      used to evaluate kinematic and kinetic data. The design of rocker had no effect
      upon the kinematics of walking. However, using new criteria for kinetic
      assessment of rocker function (tibial floor angular velocity and centre of
      pressure progression), most designs had a deleterious effect on the biomechanics
      of gait. Only two rockers approached the ideal kinetic criteria.

PMID- 1991787
TI  - Long-term results of the Evans procedure for lateral instability of the ankle.
AB  - We studied the late outcome of 40 ankles (from a consecutive series of 42)
      treated by a modified Evans procedure. The peroneus brevis tendon was used to
      fashion a static tenodesis. All the patients had suffered from persistent lateral
      instability following an ankle sprain. The follow-up period was between nine and
      12 years. Excellent or good results were achieved in 33 ankles (82.5%), three had
      a fair result, and four were poor. The clinical results were matched by the
      radiographic results which showed significant talar tilt or anterior talar
      translation in only three ankles. The functional result showed no positive
      correlation with the stress-radiographic analysis. We concluded that this
      modification of the Evans operation gives satisfactory long-term results, which
      show little change from the good results at 24 to 35 months reported in an
      earlier paper from our department.

PMID- 1991788
TI  - Regulated and constitutive protein targeting can be distinguished by secretory
      polarity in thyroid epithelial cells.
AB  - We have studied concurrent apical/basolateral and regulated/constitutive
      secretory targeting in filter-grown thyroid epithelial monolayers in vitro, by
      following the exocytotic routes of two newly synthesized endogenous secretory
      proteins, thyroglobulin (Tg) and p500. Tg is a regulated secretory protein as
      indicated by its acute secretory response to secretagogues. Without stimulation,
      pulse-labeled Tg exhibits primarily two kinetically distinct routes: less than or
      equal to 80% is released in an apical secretory phase which is largely complete
      by 6-10 h, with most of the remaining Tg retained in intracellular storage from
      which delayed apical discharge is seen. The rapid export observed for most Tg is
      unlikely to be because of default secretion, since its apical polarity is
      preserved even during the period (less than or equal to 10 h) when p500 is
      released basolaterally by a constitutive pathway unresponsive to secretagogues.
      p500 also exhibits a second, kinetically distinct secretory route: at chase times
      greater than 10 h, a residual fraction (less than or equal to 8%) of p500 is
      secreted with an apical preponderance similar to that of Tg. It appears that this
      fraction of p500 has failed to be excluded from the regulated pathway, which has
      a predetermined apical polarity. From these data we hypothesize that a targeting
      hierarchy may exist in thyroid epithelial cells such that initial sorting to the
      regulated pathway may be a way of insuring apical surface delivery from one of
      two possible exocytotic routes originating in the immature storage compartment.

PMID- 1991789
TI  - Modulation of hexokinase association with mitochondria analyzed with quantitative
      three-dimensional confocal microscopy.
AB  - Hexokinase isozyme I is proposed to be associated with mitochondria in vivo.
      Moreover, it has been suggested that this association is modulated in
      coordination with changes in cell metabolic state. To test these hypotheses, we
      analyzed the subcellular distribution of hexokinase relative to mitochondria in
      paraformaldehyde-fixed astrocytes using immunocytochemistry and quantitative
      three-dimensional confocal microscopy. Analysis of the extent of colocalization
      between hexokinase and mitochondria revealed that approximately 70% of cellular
      hexokinase is associated with mitochondria under basal metabolic conditions. In
      contrast to the immunocytochemical studies, between 15 to 40% of cellular
      hexokinase was found to be associated with mitochondria after fractionation of
      astrocyte cultures depending on the exact fractionation conditions. The
      discrepancy between fractionation studies and those based on imaging of
      distributions in fixed cells indicates the usefulness of using techniques that
      can evaluate the distributions of "cytosolic" enzymes in cells whose subcellular
      ultrastructure is not severely disrupted. To determine if hexokinase distribution
      is modulated in concert with changes in cell metabolism, the localization of
      hexokinase with mitochondria was evaluated after inhibition of glucose metabolism
      with 2-deoxyglucose. After incubation with 2-deoxyglucose there was an
      approximate 35% decrease in the amount of hexokinase associated with
      mitochondria. These findings support the hypothesis that hexokinase is bound to
      mitochondria in rat brain astrocytes in vivo, and that this association is
      sensitive to cell metabolic state.

PMID- 1991790
TI  - The cytoskeleton of the resting human blood platelet: structure of the membrane
      skeleton and its attachment to actin filaments.
AB  - We used high-resolution EM and immunocytochemistry in combination with different
      specimen preparation techniques to resolve the ultrastructure of the resting
      platelet cytoskeleton. The periphery of the cytoskeleton, an electron-dense
      subplasmalemmal region in thin section electron micrographs, is a tightly woven
      planar sheet composed of a spectrin-rich network whose interstices contain
      GPIb/IX-actin-binding protein (ABP) complexes. This membrane skeleton connects to
      a system of curved actin filaments (F-actin) that emanate from a central oval
      core of F-actin cross-linked by ABP. The predominant interaction of the radial
      actin filaments with the membrane skeleton is along their sides, and the
      strongest connection between the membrane skeleton and F-actin is via ABP-GPIb
      ligands, although there is evidence for spectrin attaching to the ends of the
      radial actin filaments as well. Since a mechanical separation of the F-actin
      cores and radial F-actin-GPIb-ABP complexes from the underlying spectrin-rich
      skeleton leads to the latter's expansion, it follows that the spectrin-based
      skeleton of the resting cell may be held in a compressed form by interdigitating
      GPIb/IX complexes which are immobilized by radial F-actin-ABP anchors.

PMID- 1991792
TI  - The axonally secreted protein axonin-1 is a potent substratum for neurite growth.
AB  - Axonin-1 is a neuronal glycoprotein occurring both as a membrane-bound and a
      secreted form. Membrane-bound axonin-1 is predominantly located in membranes of
      developing nerve fiber tracts and has recently been characterized as a cell
      adhesion molecule; the soluble form is secreted from axons and accumulates in the
      cerebrospinal fluid and the vitreous fluid of the eye. In the present study, we
      addressed the question as to whether secreted axonin-1 was released in a
      functionally competent form and we found that it strongly promotes neurite
      outgrowth when presented to neurons as an immobilized substratum. Neurite lengths
      elaborated by embryonic dorsal root ganglia neurons on axonin-1 were similar to
      those on the established neurite-promoting substrata L1 and laminin. Fab
      fragments of axonin-1 antibodies completely inhibited neurite growth on axonin-1,
      but not on other substrata. In soluble form, axonin-1 had an anti-adhesive
      effect, as revealed by perturbation of neurite fasciculation. In view of their
      structural similarity, we conclude that secreted and membrane-bound axonin-1
      interact with the same growth-promoting neuritic receptor. The fact that secreted
      axonin-1 is functionally active, together with our previous findings that it is
      secreted from an internal cellular pool, suggests a functional dualism between
      membrane-bound and secreted axonin-1 at the site of secretion, which is most
      likely the growth cone. The secretion of adhesion molecules could represent a
      powerful and rapidly acting regulatory element of growth cone-neurite
      interactions in the control of neurite elongation, pathway selection, and
      possibly target recognition.

PMID- 1991791
TI  - Centrophilin: a novel mitotic spindle protein involved in microtubule nucleation.
AB  - A novel protein has been identified which may serve a key function in nucleating
      spindle microtubule growth in mitosis. This protein, called centrophilin, is
      sequentially relocated from the centromeres to the centrosomes to the midbody in
      a manner dependent on the mitotic phase. Centrophilin was initially detected by
      immunofluorescence with a monoclonal, primate-specific antibody (2D3) raised
      against kinetochore-enriched chromosome extract from HeLa cells (Valdivia, M. M.,
      and B. R. Brinkley. 1985. J. Cell Biol. 101:1124-1134). Centrophilin forms
      prominent crescents at the poles of the metaphase spindle, gradually diminishes
      during anaphase, and bands the equatorial ends of midbody microtubules in
      telophase. The formation and breakdown of the spindle and midbody correlates in
      time and space with the aggregation and disaggregation of centrophilin foci.
      Immunogold EM reveals that centrophilin is a major component of pericentriolar
      material in metaphase. During recovery from microtubule inhibition, centrophilin
      foci act as nucleation sites for the assembly of spindle tubules. The 2D3 probe
      recognizes two high molecular mass polypeptides, 180 and 210 kD, on immunoblots
      of whole HeLa cell extract. Taken together, these data and the available
      literature on microtubule dynamics point inevitably to a singular model for
      control of spindle tubule turnover.

PMID- 1991794
TI  - 1991 International Chromatography Guide.

PMID- 1991793
TI  - Gene expression and extracellular matrix ultrastructure of a mineralizing
      chondrocyte cell culture system.
AB  - Conditions were defined for promoting cell growth, hypertrophy, and extracellular
      matrix mineralization of a culture system derived from embryonic chick vertebral
      chondrocytes. Ascorbic acid supplementation by itself led to the hypertrophic
      phenotype as assessed by respective 10- and 15-fold increases in alkaline
      phosphatase enzyme activity and type X synthesis. Maximal extracellular matrix
      mineralization was obtained, however, when cultures were grown in a nutrient
      enriched medium supplemented with both ascorbic acid and 20 mM beta
      glycerophosphate. Temporal studies over a 3-wk period showed a 3-4-fold increase
      in DNA accompanied by a nearly constant DNA to protein ratio. In this period,
      total collagen increased from 3 to 20% of the cell layer protein; total calcium
      and phosphorus contents increased 15-20-fold. Proteoglycan synthesis was maximal
      until day 12 but thereafter showed a fourfold decrease. In contrast, total
      collagen synthesis showed a greater than 10-fold increase until day 18, a result
      suggesting that collagen synthesis was replacing proteoglycan synthesis during
      cellular hypertrophy. Separate analysis of individual collagen types demonstrated
      a low level of type I collagen synthesis throughout the 21-d time course.
      Collagen types II and X synthesis increased during the first 2 wk of culture;
      thereafter, collagen type II synthesis decreased while collagen type X synthesis
      continued to rise. Type IX synthesis remained at undetectable levels throughout
      the time course. The levels of collagen types I, II, IX, and X mRNA and the large
      proteoglycan core protein mRNA paralleled their levels of synthesis, data
      indicating pretranslational control of synthesis. Ultrastructural examination
      revealed cellular and extracellular morphology similar to that for a developing
      hypertrophic phenotype in vivo. Chondrocytes in lacunae were surrounded by a well
      formed extracellular matrix of randomly distributed collagen type II fibrils
      (approximately 20-nm diam) and extensive proteoglycan. Numerous vesicular
      structures could be detected. Cultures mineralized reproducibly and crystals were
      located in extracellular matrices, principally associated with collagen fibrils.
      There was no clear evidence of mineral association with extracellular vesicles.
      The mineral was composed of calcium and phosphorus on electron probe
      microanalysis and was identified as a very poorly crystalline hydroxyapatite on
      electron diffraction. In summary, these data suggest that this culture system
      consists of chondrocytes which undergo differentiation in vitro as assessed by
      their elevated levels of alkaline phosphatase and type X collagen and their
      ultrastructural appearance.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1991795
TI  - Clinical review 18: Are patients with acromegaly at increased risk for neoplasia?

PMID- 1991796
TI  - The hypothalamic-pituitary-adrenal cortical axis in mental disorders.

PMID- 1991797
TI  - Pituitary size in depression.
AB  - Magnetic resonance images centered at the pituitary stalk were used to measure
      pituitary gland size in 19 patients with major depression compared with that in
      age- and sex-matched controls. Depressed patients had significantly greater
      pituitary cross-sectional area (P = 0.0009) and volume (P = 0.007) than the
      controls. This difference was particularly prominent in elderly depressed
      patients compared to elderly controls. These results provide the first
      demonstration of structural alterations in the pituitary gland in major
      depression.

PMID- 1991798
TI  - Insulin resistance of puberty: a defect restricted to peripheral glucose
      metabolism.
AB  - To examine mechanisms underlying the development of insulin resistance during
      normal puberty, sequential 8 and 40 mU/m2.min euglycemic insulin clamp and
      hyperglycemic clamp studies were performed in 14 healthy prepubertal and 19
      pubertal children. Both groups had comparable rates of glucose turnover and
      plasma levels of branched chain amino acids and FFA at baseline. The low as well
      as the high insulin dose stimulated peripheral glucose uptake much more
      effectively in prepubertal children (P less than 0.05). In contrast, suppression
      of hepatic glucose production (60% at low dose in both groups, pNS) and lowering
      of substrates in response to insulin was not affected by puberty at either dose.
      During the hyperglycemic clamp pubertal children showed enhanced insulin
      responses and in turn a sharper fall in amino acids (P less than 0.05 vs.
      prepubertals). Our data suggest that insulin resistance during puberty is
      restricted to peripheral glucose metabolism. Selective insulin resistance leading
      to compensatory hyperinsulinemia may serve to amplify insulin's effect on amino
      acid metabolism, thereby facilitating protein anabolism during this period of
      rapid growth.

PMID- 1991799
TI  - Effects of estropipate treatment on plasma lipids and lipoprotein lipid
      composition in postmenopausal women.
AB  - It is generally believed that the cardioprotective benefit of long term treatment
      of postmenopausal women with estrogen results in part from its capacity to
      increase high density lipoprotein (HDL) and lower low density lipoprotein (LDL)
      concentrations. The extent to which the various estrogens employed in replacement
      treatment affect the composition of lipoproteins, however, is not known. For this
      reason, we have examined the impact of one such preparation, the synthetic
      estrone estropipate (1.25 mg/day), on lipoprotein levels and composition in six
      postmenopausal women. After 6 months of treatment, whole plasma triglyceride
      (pretreatment, 135 +/- 63; posttreatment, 143 +/- 56 mg/dL), cholesterol
      (pretreatment, 232 +/- 14; posttreatment, 216 +/- 29 mg/dL), and HDL-C
      (pretreatment, 57.8 +/- 14.8; posttreatment, 55.6 +/- 13.2) were unchanged.
      However, plasma free (unesterified) cholesterol (FC) fell (pretreatment, 73.4 +/-
      6.2; posttreatment, 53.7 +/- 9.3 mg/dL; P less than 0.05) and lecithin (L) rose
      significantly (pretreatment, 2.12 +/- 0.29; posttreatment, 2.47 +/- 0.34
      mumol/mL; P less than 0.01). The consequence of these changes was a significant
      decline in the plasma FC/L ratio (pretreatment, 0.91 +/- 0.17; posttreatment,
      0.68 +/- 0.12; P less than 0.01) to levels observed in healthy menstruating
      women. The calculated lipoprotein particle size was unchanged in very low density
      lipoproteins and increased significantly (P less than 0.05) in LDL after
      estropipate therapy. Since qualitatively altered lipoproteins enriched in FC and
      an increased FC/L ratio in plasma are both associated with increased coronary
      risk, the improvement noted in these parameters after estropipate therapy
      indicates that its use may be beneficial despite the lack of change in whole
      plasma lipids.

PMID- 1991800
TI  - Dynamics of pulsatile prolactin release during the postpartum lactational period.
AB  - To investigate the pulsatile nature of PRL release in the physiologically
      hyperprolactinemic postpartum period, we sampled blood at 10-min intervals for 24
      h in each of 6 healthy lactating women at both 3 weeks and 3 months postpartum.
      The subsequent immunoactive PRL time series were subjected to episodic peak
      detection (Cluster analysis) and multiple parameter deconvolution analysis. The
      24-h mean serum PRL concentrations were significantly higher at 3 weeks than at 3
      months postpartum; viz. 113 +/- 12 vs. 66 +/- 15 micrograms/L (P = 0.003).
      Assessment of episodic PRL pulsatility revealed significantly higher maximal PRL
      peak heights (296 +/- 63 vs. 141 +/- 44 micrograms/L), fractional peak heights
      (863 +/- 150 vs. 374 +/- 58%), incremental peak amplitudes (250 +/- 60 vs. 96 +/-
      3 micrograms/L), and peak areas (13 +/- 3 vs. 4 +/- 1 mg/L.min) in the earlier
      postpartum period. In contrast, PRL peak frequencies and interpulse intervals
      were not different in the early and late postpartum sessions. Deconvolution
      analysis revealed that the mean mass of PRL secretory bursts was significantly
      greater at 3 weeks (182 +/- 4.1 micrograms/L) than 3 months (15 +/- 1.6
      micrograms/L). There were no changes in the calculated half-life of endogenous
      PRL viz. 29 +/- 2.5 min (3 weeks) vs. 26 +/- 3.0 min (3 months). We conclude that
      physiological postpartum hyperprolactinemia is achieved by selectively altering
      the endogenous secretory rate in each PRL release episode, with no change in the
      number of bursts of PRL discharged or the PRL half-life.

PMID- 1991801
TI  - Low growth hormone levels are related to increased body mass index and do not
      reflect impaired growth in luteinizing hormone-releasing hormone agonist-treated
      children with precocious puberty.
AB  - To test the hypothesis that GH deficiency might explain the low growth velocity
      of some LHRH agonist (LHRHa)-treated children with central precocious puberty, we
      measured stimulated (n = 81) and spontaneous (n = 32) GH levels during or after
      LHRHa treatment. GH stimulation tests in the children who were receiving LHRHa
      treatment were performed after 2 days of ethinyl estradiol administration. Thirty
      one of 81 children (38%) who underwent GH stimulation tests had subnormal
      responses (less than or equal to 7 micrograms/L) to all tests administered (at
      least 2 stimuli), including 22 of 67 (33%) who had precocious puberty that was
      idiopathic or associated with hypothalamic hamartoma. Eleven of 32 children (34%)
      who underwent measurement of the mean nighttime spontaneous GH level had levels
      below the normal range for prepubertal children (less than 1.2 microgram/L).
      Despite the high incidence of subnormal GH levels, there appeared to be no
      relationship between the GH levels of these children and their growth
      characteristics. The height, growth velocity, bone maturation rate, predicted
      height, and insulin-like growth factor-I levels were not different between the
      children with low GH levels and the children with normal GH levels. Conversely,
      the GH levels were not different between the children with subnormal growth rates
      and the children with normal growth rates. Thus, variation in the growth rates of
      these LHRHa-treated children with central precocious puberty could not be
      explained by variation in the stimulated or spontaneous secretion of GH. In
      attempting to understand the high incidence of low GH levels in children with
      precocious puberty, we examined the relationship between GH level and body mass
      index (BMI). Both the stimulated (r = -0.33; P less than 0.002) and the
      spontaneous (r = -0.61; P less than 0.0002) GH levels were inversely related to
      BMI. Moreover, the children with precocious puberty as a group had significantly
      elevated BMI [1.2 +/- 0.1 (+/- SE) SD units] compared to normal children of the
      same age (P less than 0.0001). Thus, increased body mass may explain the high
      incidence of subnormal GH levels in these patients, and normative GH levels
      adjusted for body mass are needed before it can be concluded that the apparently
      subnormal GH levels in LHRHa-treated children with precocious puberty are in fact
      low.

PMID- 1991802
TI  - Effects of glucagon on free fatty acid metabolism in humans.
AB  - To determine whether physiological changes in plasma glucagon concentrations are
      important in regulating basal adipose tissue lipolysis, FFA flux ([1
      14C]palmitate) was measured in response to increases and decreases in plasma
      glucagon. Eight volunteers with insulin-dependent diabetes mellitus (IDDM) and
      nine healthy nondiabetic volunteers were studied using the pancreatic clamp
      technique to control plasma insulin, GH, and glucagon concentrations at desired
      levels. Palmitate flux at the chosen euglucagonemic hormone infusion rates was
      similar to baseline values (1.73 +/- 0.12 vs. 1.75 +/- 0.23 and 1.35 +/- 0.18 vs.
      1.35 +/- 0.16 mumol/kg.min, respectively, in IDDM and nondiabetic subjects). No
      significant changes in palmitate flux occurred in response to glucagon withdrawal
      or mild (nondiabetic volunteers) or high physiological (IDDM volunteers)
      hyperglucagonemia. Thus, under conditions of normal FFA availability, changes in
      plasma glucagon concentrations within the physiological range have little or no
      effect on adipose tissue lipolysis.

PMID- 1991803
TI  - Determination of plasma calcitonin gene-related peptide concentrations by a new
      immunochemiluminometric assay in normal persons and patients with medullary
      thyroid carcinoma and other neuroendocrine tumors.
AB  - There is doubt about concentrations of circulating calcitonin gene-related
      peptide (CGRP) and the value of plasma CGRP measurements in the detection and
      follow-up of medullary thyroid carcinoma (MTC). Thus, we developed an
      immunochemiluminometric sandwich assay for CGRP using antibodies purified from a
      polyclonal antiserum against human CGRP. The assay was sensitive (limit of
      detection, 0.4 pmol/L; multiply by 3.7892 to derive nanograms per L) and highly
      specific [no cross-reaction with human calcitonin (CT)]. Normal plasma CGRP
      values ranged from less than 0.4 to 4.5 pmol/L (median, 0.8; n = 31), with 61%
      having detectable levels. Values in samples from patients with MTC were elevated:
      unoperated patients (n = 10), 4.7-137 pmol/L (median, 7.1); and operated patients
      with gross persistent or recurrent tumor (n = 14), 4.7-171 pmol/L (median, 23.2).
      In contrast, CGRP values were normal in 78% of nine postoperative patients with
      elevated CT, but no detectable tumor (range, less than 0.4 to 6.3 pmol/L; median,
      1.6). CGRP levels increased after pentagastrin injection in MTC patients, but
      less than did CT values. Cultured MTC cells in vitro secreted large amounts of
      CGRP, and rat nerve root ganglia, human osteoblasts, and microvessel endothelial
      cells secreted lesser amounts. We conclude that CGRP circulates in normal plasma,
      but at very low levels. Plasma CGRP concentrations are frequently high in
      patients with MTC, but primarily in those with gross tumor or metastases. Plasma
      CT assay is the preferable test for MTC, but CGRP assay deserves prospective
      study for a possible role in predicting gross metastasis.

PMID- 1991804
TI  - Parathyroid function in normocalcemic renal transplant recipients: evaluation by
      calcium infusion.
AB  - The extent to which secondary hyperparathyroidism may involute remains poorly
      defined. Renal transplantation offers a clinical situation in which metabolic
      stimuli for hyperparathyroidism are removed. To examine whether
      hyperparathyroidism resolves after transplantation, we evaluated 11 renal
      transplant recipients who had been normocalcemic 6 or more months after
      transplantation using a sensitive 2-site immunoradiometric assay for intact serum
      PTH. Nine of the 11 had PTH concentrations within the normal range. Of these 9, 6
      were found to have abnormal parathyroid function when challenged with an iv
      calcium infusion. The other 2 patients demonstrated significantly elevated basal
      PTH concentrations and elevated ionized calcium despite normal total serum
      calcium and albumin concentrations. In both, the PTH response to infused calcium
      was markedly abnormal, confirming hyperparathyroidism. The estimated renal
      threshold phosphate concentration was low in 4 of 9 patients with normal basal
      PTH concentrations and in both with elevated basal PTH. Bone mineral density,
      measured at the radius by single photon absorptiometry and at the spine by dual
      energy x-ray absorptiometry, was normal in 8 of the 9 transplant recipients who
      had normal basal PTH concentrations.

PMID- 1991805
TI  - Expression of messenger ribonucleic acids that encode for 3 beta-hydroxysteroid
      dehydrogenase and cholesterol side-chain cleavage enzyme throughout the luteal
      phase of the macaque menstrual cycle.
AB  - To study further the control of the primate corpus luteum, we obtained corpora
      lutea from cynomolgus macaques at defined stages of the luteal phase and examined
      steady state mRNA levels in these corpora lutea by Northern analysis for the two
      major enzymes involved in progesterone biosynthesis, cytochrome P450 cholesterol
      side-chain cleavage (P450SCC) and 3 beta-hydroxysteroid dehydrogenase (3 beta
      HSD). mRNAs for both P450SCC and 3 beta HSD were maximal or near maximal shortly
      after ovulation and luteinization (days 3-5 of the luteal phase). mRNA for
      P450SCC exhibited a slight, but nonsignificant (P greater than 0.05) decline
      throughout the remainder of the luteal phase and was undetectable upon luteal
      regression. Steady state levels of 3 beta HSD mRNA were significantly lower (P
      less than 0.05) from corpora lutea removed during the midluteal phase (days 7-8
      of the luteal phase) than those in newly formed corpora lutea and declined to 10%
      of early luteal phase values by days 13-15 of the luteal phase. 3 beta HSD mRNA
      levels fell to nondetectable values upon luteal regression. These results reveal
      a paradoxical relationship between the steroidogenic activity of the primate
      corpus luteum in vivo and the steady state levels of the mRNAs that encode for
      the major enzymes involved in progesterone biosynthesis. Unlike serum
      progesterone concentrations, which are very low immediately after ovulation and
      then rise during the midluteal phase, the steady stale levels of P450SCC mRNA and
      3 beta HSD appeared to be maximal or near maximal shortly after ovulation and
      declined throughout the remainder of the luteal phase. These findings are
      consistent with the notion that luteal lifespan is set at the time of ovulation
      and luteinization, and the decline in luteal function may be due in part to decay
      of specialized luteal cell mRNAs with finite half-lives.

PMID- 1991806
TI  - Effect of menopause and hormone replacement therapy on the urinary excretion of
      pyridinium cross-links.
AB  - Pyridinoline (Pyr) and deoxypyridinoline (D-Pyr) are two cross-links of collagen
      molecules that are present in the extracellular matrix and released during its
      degradation. In contrast to the wide distribution of collagen, Pyr is present in
      bone and cartilage, but not in significant amounts in other connective tissues,
      and D-Pyr appears to be specific for bone tissue. Therefore, the urinary
      excretion of Pyr and D-Pyr might be a sensitive marker of bone matrix
      degradation. Using a specific high pressure liquid chromatography assay we have
      measured Pyr and D-Pyr cross-links in a 24-h and a fasting urine sample in 60
      early postmenopausal women and 19 premenopausal women matched for age. Menopause
      induced a 62% increase in Fu Pyr (49.8 +/- 18.7 vs. 30.8 +/- 8.0 pmol/mumol
      creatinine; P less than 0.001) and an 82% increase in Fu D-Pyr (8.2 +/- 3.4 vs.
      4.5 +/- 1.4 pmol/mumol creatinine; P less than 0.001). In 20 postmenopausal women
      on hormone replacement therapy, urinary Pyr and D-Pyr returned to premenopausal
      levels within 6 months, contrasting with unchanged levels during placebo
      treatment. The 24-h excretion of Pyr and D-Pyr was significantly lower than the
      fasting excretion, but was similarly decreased after hormone replacement therapy.
      Pyr and D-Pyr excretion measured in the same urinary sample were highly
      correlated (r = 0.85 for fasting and 0.83 for 24-h sampling), but correlations
      between fasting and 24-h values were weak (D-Pyr, r = 0.30; Pyr, r = 0.29; P less
      than 0.05 for both). Correlations between urinary cross-links and other markers
      of bone turnover (Fu hydroxyproline/creatinine and plasma osteocalcin) were
      significant but low (Pyr vs. osteocalcin, r = 0.29, P less than 0.05; Pyr vs.
      hydroxyproline, r = 0/.34; P less than 0.01; D-Pyr vs. osteocalcin, r = 0.39; P
      less than 0.01), except for D-Pyr vs. hydroxyproline (r = 0.24; P = 0.07),
      suggesting that these markers reflect different events of bone metabolism.
      Finally, a single measurement of the fasting excretion, but not of the 24-h
      excretion, of cross-links was significantly correlated (Pyr, r = 0.34; P less
      than 0.05; D-Pyr, r = -0.46; P less than 0.01), with the subsequent spontaneous
      rate of bone loss assessed by repeated measurements of the radial bone mineral
      content in 37 postmenopausal women.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1991807
TI  - Contrasting effects of oral and transdermal routes of estrogen replacement
      therapy on 24-hour growth hormone (GH) secretion, insulin-like growth factor I,
      and GH-binding protein in postmenopausal women.
AB  - Estrogen deficiency may account for lower circulating GH and insulin-like growth
      factor I (IGF-I) concentrations in the menopause. Since the liver is the major
      source of circulating IGF-I and oral estrogens have nonphysiological effects on
      hepatic function, we have compared GH secretion over 24 h from 20 min sampling
      and serum IGF-I levels in premenopausal women (n = 7, follicular phase) and
      postmenopausal women before and after 2 months of cyclical replacement therapy
      with either oral ethinyl estradiol (EE, 20 micrograms daily; n = 7) or
      transdermal 17 beta-estradiol (E2, 100 micrograms patches applied twice weekly; n
      = 7). The extent of GH binding to its serum binding protein was also examined by
      measuring the percent specific binding of [125I] GH in serum. Mean 24-h serum GH
      and serum IGF-I were significantly lower (P less than 0.05) in postmenopausal
      than in premenopausal women. Oral and transdermal estrogen therapy resulted in a
      comparable degree of gonadotropin suppression. Oral EE treatment increased mean
      24-h serum GH (2.0 +/- 0.4 to 7.0 +/- 0.6 mIU/L, P less than 0.0005) and mean
      pulse amplitude (5.3 +/- 1.2 to 11.2 +/- 2.5 mIU/L, P less than 0.01) but
      significantly reduced circulating IGF-I (0.70 +/- 0.09 to 0.47 +/- 0.04 U/mL, P
      less than 0.02) levels. Oral EE increased the percent specific binding of
      [125I]GH (22.0 +/- 1.6 to 32.0 +/- 1.9%, P less than 0.0005), however the derived
      mean 24-h free serum GH concentrations were significantly higher (P less than
      0.0005) after treatment. By contrast, transdermal E2 administration, which
      restored circulating E2 concentrations to the midfollicular range, increased
      circulating IGF-I (0.86 +/- 0.15 to 1.10 +/- 0.14 U/mL, P less than 0.005) to
      levels that were not significantly different from those of premenopausal women
      (1.41 +/- 0.21 U/mL). This was not accompanied by changes in 24-h GH secretion or
      the percent specific binding of [125I]GH in serum. The route of administration is
      a major determinant of the effects of exogenous estrogens on the GH/IGF-I axis.
      Oral estrogen administration inhibits hepatic IGF-I synthesis and increases GH
      secretion through reduced feedback inhibition. Reduced GH secretion in the
      menopause is not explained by estrogen deficiency since GH secretion is not
      restored by the attainment of physiological E2 concentrations using the
      transdermal route. The contrasting route dependent IGF-I responses have important
      implications for the long-term benefit of hormone replacement therapy in the
      menopause.

PMID- 1991808
TI  - The course of biochemical parameters of bone turnover during treatment with
      corticosteroids.
AB  - The mechanisms by which glucocorticoids cause osteopenia are incompletely
      understood. It is generally accepted that bone formation is depressed during
      corticosteroid treatment, but the cause of the ongoing bone resorption is less
      clear. Secondary hyperparathyroidism and changes in vitamin D metabolism are
      thought to play a role. This is based mostly on data from cross-sectional studies
      in heterogeneous patient groups. We, therefore, studied longitudinally the course
      of biochemical parameters and the hormones influencing bone turnover in a
      homogeneous group of 10 euthyroid patients with Graves' ophthalmopathy, all
      euthyroid for at least 1 yr before, during, and after a 12-week course of
      prednisone. Bone formation was depressed as reflected by a fall in serum
      osteocalcin (3.0 +/- 2.1, 1.7 +/- 1.1, and 2.4 +/- 1.9 micrograms/L at weeks 0,
      4, and 12, respectively; P = 0.02) and in total alkaline phosphatase (1.15 +/-
      0.33, 0.83 +/- 0.22, and 0.88 +/- 0.40 mukat/L; P = 0.001). Parameters of bone
      resorption (urinary hydroxyproline/creatinine ratio, serum acid phosphatase) and
      the levels of vitamin D metabolites remained unchanged. Serum intact PTH seemed
      to decrease slightly. Our findings suggest that glucocorticoid induced osteopenia
      is caused by a depressed bone formation in the presence of an unaltered but
      ongoing bone resorption. Secondary hyperparathyroidism and changes in vitamin D
      metabolism are apparently not involved.

PMID- 1991809
TI  - Effects of growth hormone-binding proteins on serum growth hormone measurements.
AB  - GH-binding proteins (GH-BPs) in human blood theoretically may interfere with
      measurements of immunoreactive GH by forming complexes with GH and competing with
      antibody reagents for ligand. Indeed, results of serum GH obtained by
      immunoassays are known to differ markedly depending on the assay employed. To
      assess the potential role of circulating GH-BPs in this phenomenon, we
      systematically examined their effect on GH measurement in four RIAs and two
      immunoradiometric assays. In all except one RIA, the effect of the BPs on tracer
      binding to antibody was mildly inhibitory. In both immunoradiometric assays, BPs
      increased the nonspecific association of the tracer with the solid phase reagent.
      However, these effects were minor at the BP concentrations realistically
      encountered in practice. Furthermore, the impact of BPs on GH standard curves and
      final results was negligible because BP effects fall into the category of
      nonspecific or zero dose counts, which are subtracted during data reduction. We
      conclude that GH-BPs are only a minor disturbance in GH immunoassays, which is
      completely compensated for by conventional assay design. Disparities among
      results yielded by different assays are probably not due to BP interference.

PMID- 1991810
TI  - Evidence for a renal calcium leak in postmenopausal women.
AB  - We have measured calcium, albumin, globulin, bicarbonate, and anion gap in the
      plasma; and calcium, sodium, and creatinine in the urine, in 115 premenopausal
      and 140 postmenopausal normal women after an overnight fast, and calculated the
      calcium fractions in the plasma and the calcium/and sodium/creatinine ratios in
      the urine. The total ultrafiltrable calcium was significantly higher in the
      postmenopausal group, mainly due to their higher complexed calcium fraction, due
      in turn to their higher bicarbonate and anion gap concentrations. Urinary calcium
      was also significantly higher in the postmenopausal group even after correcting
      for sodium. After matching for total calcium and each of the calcium fractions in
      turn, the urinary calcium remained significantly higher in the post- than in the
      premenopausal sets even after correction for sodium. The implication is that the
      rise in urinary calcium at the menopause is due to reduced tubular reabsorption
      of calcium rather than to an increase in filtered load. We suggest that estrogens
      promote tubular reabsorption of calcium and that the rise in bone resorption at
      the menopause could be accounted for, at least in part, by the effect of estrogen
      deficiency on the kidney.

PMID- 1991811
TI  - An insight into early reproductive processes through the in vivo model of ovum
      donation.
AB  - To gain insight into early reproductive processes we have prospectively designed
      ovum donation protocols to elucidate several phenomena relating to embryo
      implantation and pregnancy sustenance. Artificial endometrial cycles with
      variable follicular phases were induced in 60 recipients by sequential estrogen
      and progesterone. A total of 964 oocytes were retrieved throughout 43 ovum
      donation attempts, for an average of 22.4 (range, 16-41) eggs/retrieval. The
      overall delivery rate per egg retrieval (donors and recipients combined) was
      72.1% (31 of 43). The shortest estrogen stimulation (short follicular phase)
      resulting in ongoing pregnancies was 5 days in duration, while the longest (long
      follicular phase) was 35 days in duration before progesterone initiation.
      Utilization of variable length follicular phases, artificially extended the stage
      of endometrial receptivity to over 4 weeks. To assess the window of implantation,
      same age embryos were transferred onto endometrium of different maturational
      stages. Pregnancies were documented with embryo transfers between luteal day 1
      (day 15) to luteal day 6 (day 20), extending the window of implantation in the
      human to at least 6 consecutive days. To evaluate the relative contribution of
      oocyte quality and endometrial receptivity to pregnancy outcome, common source
      ova were transferred onto endometrium with variable hormonal exposure. Despite
      the drastically different follicular phase estradiol levels and periods of
      exposure, similar delivery rates were attained in donor cycles (29.4%) and
      recipient cycles during short follicular phases (29.6%). Slightly higher delivery
      rates (39.4%) were observed with long follicular phases. The comparable pregnancy
      rates in donors and recipients are attributed to the common source oocytes
      regardless of endometrial stimulation.

PMID- 1991812
TI  - Acute changes in serum osteocalcin during induced hypocalcemia in humans.
AB  - Although levels of serum osteocalcin are thought to be an indicator of
      osteoblastic activity and bone formation, there is little information regarding
      the acute effects of changes in calcium or PTH levels on circulating osteocalcin
      concentrations. To study the effect of stepwise decreases in ionized calcium
      (CaI) on osteocalcin levels, we infused six normal subjects with citrate for four
      30-min intervals using two different protocols. One protocol (pulse infusion)
      used alternating rates of infusion and resulted in rapid stepwise decrements in
      serum CaI. The second protocol (continuous infusion) used constant intermediate
      rates of citrate infusion and produced slower decrements in CaI, but with similar
      changes in magnitude. We monitored serum CaI, intact PTH, and osteocalcin
      concentrations during the course of these infusions. During each step of the
      pulse infusion the osteocalcin responses to changes in CaI in general were
      parallel to the changes in PTH (r = 0.462; P = 0.02) and were inversely
      correlated to CaI (r = -0.562; P = 0.003). The osteocalcin concentrations at the
      end of each 30-min period were higher than at the beginning of that period; over
      the total 120 min, osteocalcin levels rose from 3.46 +/- 0.63 to 6.88 +/- 1.08
      micrograms/L (P less than 0.05). In contrast, during the first two periods of the
      continuous infusion, osteocalcin concentrations changed slightly. Only during the
      last two periods of the continuous infusion did osteocalcin respond in a manner
      characteristic of that observed with the pulse infusion. These data indicate that
      osteocalcin concentrations in the circulation may be acutely regulated by calcium
      and/or PTH.

PMID- 1991813
TI  - Nocturnal elevation of glucose levels during fasting in noninsulin-dependent
      diabetes.
AB  - To define the spontaneous diurnal variations in glucose regulation during fasting
      in noninsulin-dependent diabetes (NIDDM), we measured circulating levels of
      glucose, insulin, C-peptide, GH, cortisol, and glucagon at 15-min intervals in 11
      patients with untreated diabetes and 7 matched control subjects studied during a
      24-h period. The rates of insulin secretion were derived from the concentrations
      of C-peptide by deconvolution using a two-compartment mathematical model for C
      peptide distribution and metabolism. In both groups of subjects, despite
      continued fasting, glucose levels stopped declining in the evening and
      subsequently rose throughout the night to reach a morning maximum. Elevated
      levels persisted until noon. The morning glucose maximum corresponded to a
      relative increase of 23.8 +/- 5.5% above the evening nadir in NIDDM patients and
      13.2 +/- 4.6% in nondiabetic subjects (P less than 0.05). In NIDDM patients,
      insulin levels and insulin secretion rates did not parallel the nocturnal glucose
      changes. In contrast, in control subjects, this nocturnal glucose rise coincided
      with a similar increase in insulin secretion rates. Cortisol concentrations in
      patients with NIDDM were higher than those in control subjects throughout the
      study period (P less than 0.001) and rose earlier in the evening than in control
      subjects, thus failing to demonstrate the normal nocturnal suppression. In both
      groups of subjects, the nighttime glucose elevation was temporally and
      quantitatively correlated with the circadian cortisol rise. GH secretion was
      increased in the evening and nighttime periods compared to the daytime values,
      and in NIDDM patients, but not in control subjects, the size of the morning
      glucose elevation was directly related to the magnitude of this increase in GH
      secretion (r = 0.88; P less than 0.01). Glucagon concentrations were similar in
      both groups of subjects and remained essentially constant throughout the study
      period. We hypothesize that the nocturnal glucose rise that occurs during fasting
      represents a normal diurnal variation in the set-point of glucose regulation
      amplified by counterregulatory mechanisms activated by the fasting condition.

PMID- 1991814
TI  - Use of m-[131I]iodobenzylguanidine in the treatment of malignant
      pheochromocytoma.
AB  - The efficacy and safety of m-[131I]iodobenzylguanidine ([131I]MIBG) were assessed
      in 15 patients with malignant pheochromocytomas in a nonrandomized, single arm
      trial, in which patients were treated with [131I]MIBG (SA, 740 megabequerel/mg)
      every 3 months. Seven of these patients had bone and soft tissue metastases, 4
      had only soft metastases, and 4 had only bone metastases. The follow-up period
      ranged from 6-54 months; the number of doses ranged from 2-11, with 2.9 (78.4
      mCi) to 9.25 gigabequerel (GBq) (250 mCi)/administration and a cumulative
      activity from 11.1-85.90 GBq (300-2322 mCi). The absorbed cumulative dose in
      tumors ranged from 12-155 Gy. A beneficial effect of the treatment was observed
      in 9 patients (60%). No complete remission of the disease was observed. Seven
      patients died during the study, among whom 4 never responded to the treatment.
      Seven had hormonal responses (4 complete and 3 partial), with a duration ranging
      from 5-48 months. Among these patients, 4 relapsed, and 3 died within 3 months.
      Five patients had partial tumoral responses mainly located in soft tissues and
      for a duration ranging from 29-54 months. All patients with a hormonal response
      had objective improvement in clinical status and blood pressure. There was no
      clear-cut relationship between the cumulative dose and the responses. The main
      side-effect observed in 1 patient with widespread bone metastases after three
      doses (12.9 GBq) was a pancytopenia, which resolved after treatment was
      discontinued. This study suggests that repeated [131I]MIBG treatment could be
      effective in patients with advanced malignant pheochromocytoma.

PMID- 1991815
TI  - Correlation between serum osteocalcin and 24,25-dihydroxyvitamin D levels in
      Paget's disease of bone.
AB  - We have studied the possible correlation between serum 24,25-dihydroxyvitamin D
      [24,25-(OH)2D] and osteocalcin levels (sBGP) in Paget's disease of bone. We
      measured serum calcium, phosphate, PTH, 25-hydroxyvitamin D, 1,25-(OH)2D, 24,25
      (OH)2D, alkaline phosphatase (sAP), and the urinary hydroxyproline/creatinine
      ratio (UOH prol/creat) in 19 patients with Paget's disease of bone and 16 age-
      and sex-matched controls. As expected, sAP, UOH prol/creat, and sBGP levels were
      significantly elevated, and there was a tendency to a decrease in serum levels of
      24,25-(OH)2D in Pagetic patients with respect to the control group. There was no
      significant difference between patients and controls in serum calcium, phosphate,
      PTH, 25-hydroxyvitamin D, and 1,25-(OH)2D. The Pagetic patients were subdivided
      into two subgroups; subgroup A had normal sBGP levels (less than 5 ng/mL), and
      subgroup B had increased sBGP levels (greater than 5 ng/mL). Serum 24,25-(OH)2D
      levels in subgroup B were significantly lower than those in controls, while
      subgroup A showed levels similar to those in the control group. We also found a
      positive linear correlation between sAP and sBGP and between sAP and UOH
      prol/creat as well as a negative linear correlation between sBGP and 24,25-(OH)2D
      and between 24,25-(OH)2D and UOH prol/creat in Pagetic patients. These results
      point to a possible role of 24,25-(OH)2D in disease activity.

PMID- 1991816
TI  - Intranasal administration of neostigmine potentiates both intravenous and
      intranasal growth hormone (GH)-releasing hormone-induced GH release in short
      children.
AB  - Administration of cholinergic agonists increases both basal and GH-releasing
      hormone (GHRH)-induced GH secretion, probably acting via inhibition of endogenous
      somatostatin release. The aim of our study was to verify in two groups of
      children with idiopathic short stature the effect of intranasal administration of
      neostigmine (inNS; 3 mg), a cholinesterase inhibitor, on basal GH levels as well
      as on the somatotroph response to GHRH when the peptide was administered either
      iv (ivGHRH; 1 microgram/kg) or intranasally (inGHRH; 10 micrograms/kg). In group
      A (n = 6; age, 10.6-16.0 yr) inNS induced a significant GH increase [inNS vs.
      saline, area under the curve (AUC; mean +/- SEM), 263.7 +/- 60.2 vs. 73.8 +/- 3.1
      micrograms/L.h; P less than 0.03] and potentiated the somatotroph response to
      ivGHRH (inNS with ivGHRH vs. ivGHRH, 1316 +/- 183.0 vs. 644.9 +/- 154.5
      micrograms/L.h; P less than 0.03). In group B (n = 6; age, 11.5-15.9 yr) ivGHRH
      induced a GH rise clearly higher than that induced by inGHRH (604.2 +/- 154.3 vs.
      137.1 +/- 28.2 micrograms/L.h; P less than 0.03). Administration of inNS induced
      a GH rise similar to that occurring after inGHRH (AUC, 239.2 +/- 69.5
      micrograms/L.h) and markedly increased the inGHRH-induced GH response (482.4 +/-
      103.6 micrograms/L.h; P less than 0.05 and 0.03 vs. inNS and inGHRH,
      respectively), so that it overlapped with that induced by ivGHRH alone. In
      conclusion, cholinergic agonists such as neostigmine are able to increase both
      basal and GHRH-induced GH secretion in short children even when given
      intranasally. Combined intranasal administration of neostigmine and GHRH (10
      micrograms/kg) is able to induce a GH rise similar to that induced by ivGHRH
      alone (1 microgram/kg), suggesting the potential usefulness of this combination
      cocktail and route of administration for the treatment of short stature.

PMID- 1991817
TI  - Growth hormone-releasing hormone reverses secondary somatotroph unresponsiveness.
AB  - Twenty severely GH-deficient prepubertal children aged 10.7 +/- 2.1 yr (mean +/-
      SD) and with a height SD of -4.92 +/- 1.02 were treated with sc injections of
      GHRH 1-44 (10 micrograms/kg BW) for 6 months either daily (11 patients) or 3
      times/week (nine patients). An acute iv GHRH test (2 micrograms/kg BW) was
      performed before and after 2 and 6 months of treatment. Mean (+/- SD) peak GH
      responses to these tests were 2.92 +/- 3.01, 4.57 +/- 4.91, and 7.56 +/- 8.14
      micrograms/L, respectively (P less than 0.05, pretreatment vs. 6 months). The
      mean growth velocity (GV) during treatment was only 2.99 +/- 1.67 cm/yr and only
      two patients increased their GV by more than 2 cm/yr. A correlation was found
      between GV during treatment and the peak serum GH response to GHRH acute test
      before treatment (r = 0.68, P less than 0.005) as well as between GH response to
      the acute test and patient's bone age (r = -0.46, P less than 0.05). The results
      indicate that in some severely GHD patients with no response to GHRH even after a
      2-month priming period, 6 months of treatment with GHRH can evoke pituitary
      responsiveness. We speculate that the duration of the GHRH deficiency and its
      severity plays a role in the ability of somatotrophs to respond to this stimulus.

PMID- 1991818
TI  - Serum osteocalcin in patients taking L-thyroxine who have subclinical
      hyperthyroidism.
AB  - Serum osteocalcin, an index of osteoblastic activity, is increased in
      hyperthyroidism. Serum osteocalcin levels are negatively correlated with bone
      density in patients with overt hyperthyroidism. Osteocalcin levels are also
      elevated in patients with multinodular goiter and subclinical hyperthyroidism. We
      therefore measured serum osteocalcin levels in patients taking T4 to determine if
      they correlated with the degree of TSH suppression. Despite an upward trend in
      serum osteocalcin measurements with decreasing TSH concentrations, there was no
      significant difference in serum osteocalcin among groups of patients with normal
      (0.5-5.0 mu/L), mildly reduced (0.1-0.5 mU/L), or undetectable serum TSH (less
      than 0.01 mU/L). However, a weak negative correlation was seen between serum TSH
      and osteocalcin concentrations (r = 0.29, slope = -0.28, P less than 0.05).
      Osteocalcin did not correlate with either serum free T4 or free T3
      concentrations. Serum PTH concentrations were not different among the three
      patient groups. Our data suggest that osteocalcin is not a useful clinical marker
      for increased bone turnover in patients with subclinical hyperthyroidism due to
      T4 therapy. However, the trend towards higher osteocalcin levels in patients with
      suppressed serum TSH values, and the weak negative correlation between serum TSH
      and osteocalcin are consistent with findings of reduced bone density in these
      patients.

PMID- 1991819
TI  - Suppression of immune responses to acetylcholine receptor by interleukin 2-fusion
      toxin: in vivo and in vitro studies.
AB  - The pathogenesis of the autoimmune disease, myasthenia gravis (MG), involves an
      antibody-mediated attack against acetylcholine receptors (AChRs). Since the
      relevant antibody response is T cell dependent, a therapeutic strategy aimed at T
      lymphocytes actively participating in the immune reaction to AChR should result
      in relatively selective suppression of AChR antibody. During an active immune
      response, T cells express receptors for interleukin 2 (IL2). In this study, we
      have used a genetically engineered fusion protein comprised of the binding region
      of IL2 and the toxic portion of diphtheria toxin (DAB486-IL2), to attempt to
      treat an experimental animal model of MG in rodents. We examined the effects of
      treatment with DAB486-IL2 in vivo on primary, ongoing, and secondary antibody
      responses to purified Torpedo AChR. Treatment of mice with intraperitoneal
      injections of DAB486-IL2 beginning at the time of immunization inhibited the
      primary AChR antibody response by 50% during the treatment period. Ongoing and
      secondary antibody responses to AChR were not suppressed in vivo by treatment
      with DAB486-IL2. In comparison, DAB486-IL2 was far more potent in suppressing
      antibody responses and lymphoproliferation in cell culture. At a dose comparable
      to that given in vivo, cellular proliferation and antibody production were
      virtually eliminated in a secondary response in vitro. The suppressive effect of
      DAB486-IL2 was much more pronounced when it was given at the time of initial
      antigen stimulation, as compared with its effect when given during an already
      established antibody response. These findings suggest that the effect of the
      fusion toxin on AChR antibody production was due predominantly to inhibition of T
      cells rather than B cells.

PMID- 1991820
TI  - Antibodies to interleukin-1 inhibit cytokine-induced proliferation of neonatal
      rat Schwann cells in vitro.
AB  - Unfractionated cytokines have been shown to induce in vitro proliferation of
      neonatal rat Schwann cells but the nature of the mitogen(s) is not known. A
      mixture of rabbit antibodies specific for recombinant interleukin-1 alpha (IL-1
      alpha) and interleukin-1 beta (IL-1 beta) inhibited Schwann cell proliferation
      induced by unfractionated human cytokines whereas antibodies to interleukin-2 (IL
      2) and control IgG did not. However, purified human IL-1 and recombinant human IL
      1 alpha or beta did not induce Schwann cell proliferation on their own.

PMID- 1991821
TI  - Interleukin-6 is elevated in plasma in multiple sclerosis.
AB  - Levels of interleukin-6 (IL-6)--a cytokine which induces immunoglobulin
      production of activated B cells--were measured in cerebrospinal fluid (CSF) and
      plasma of patients with multiple sclerosis (MS), acute meningo-encephalitis (AM)
      and muscular tension headache (TH). MS patients had in repeated samples higher
      levels of IL-6 in plasma compared to patients with AM and TH. IL-6 concentrations
      in MS plasma were about 17 times higher than MS CSF, while in AM 20-fold higher
      levels were found in CSF compared to plasma during the acute stage. IL-6 in AM
      CSF decreased rapidly during clinical recovery. No correlation was found between
      IL-6 in MS patients' plasma or CSF and disease activity. The functional
      significance of elevated IL-6 concentrations in MS plasma is unknown, although
      the findings support the hypothesis of a systemic B cell response in MS.

PMID- 1991822
TI  - Antibodies to myelin-oligodendrocyte glycoprotein in cerebrospinal fluid from
      patients with multiple sclerosis and controls.
AB  - Myelin-oligodendrocyte glycoprotein (MOG) has been implicated as a target for
      antibody-mediated immune attack in experimental autoimmune encephalomyelitis
      (EAE) which has been used extensively as an experimental model of multiple
      sclerosis (MS). We have screened cerebrospinal fluid (CSF) and plasma from 30
      patients with MS, 30 with other neurological diseases (OND) and 30 with tension
      headache for anti-MOG antibodies of IgG isotype by enzyme-linked immunosorbent
      assay (ELISA). Such antibodies were detected in CSF from seven of the patients
      with MS, compared to two with OND and one with tension headache. No anti-MOG IgG
      antibodies were demonstrable in plasma. Antibody specificity was confirmed by
      Western blot immunostaining. Antibody levels were higher in MS compared to OND
      and tension headache. No correlation was observed between anti-MOG IgG antibodies
      and total IgG levels in CSF. The significance of anti-MOG antibodies demonstrated
      in MS CSF remains to be defined.

PMID- 1991823
TI  - A possible immunoregulatory function for [Met]-enkephalin-Arg6-Phe7 involving
      human and invertebrate granulocytes.
AB  - Opioid peptides and their analogs have been shown to stimulate adherence,
      conformational changes and locomotory activity in human as well as invertebrate
      granulocytes. The present study demonstrates that [Met]-enkephalin-Arg6-Phe7, an
      opioid substance thus far not included in these immunological tests, exhibits
      stimulatory effects comparable to those of [Met]-enkephalin in this regard.
      Furthermore, since neutral endopeptidase 24.11 (enkephalinase; CD10/NEP) exists
      in invertebrate immunocyte membranes, we demonstrate that its specific inhibitor,
      phosphoramidon, potentiates the effects of the heptapeptide in inducing
      conformational change in both human and invertebrate granulocytes. Additionally,
      the major metabolic products of NEP activity, Phe-Met-Arg-Phe and Tyr-Gly-Gly,
      appear to be potent antagonists of this enzyme activity, especially the
      tetrapeptide. The effects of heptapeptide stimulation showed a major difference
      between vertebrate and invertebrate immunocytes with respect to their time
      course, namely, the speed of their onset. [Met]-enkephalin-Arg6-Phe7 markedly
      stimulated the locomotory activity of these cells which becomes most noticeable
      within 15-45 min for Mytilus cells and in a 5-15 min period for human cells. It
      also enhanced the mobility and velocity of the responsive human (5 microns/min)
      and invertebrate cells (2.1 microns/min).

PMID- 1991824
TI  - New roles for rheumatoid factor.

PMID- 1991825
TI  - Polycythemia vera blood burst-forming units-erythroid are hypersensitive to
      interleukin-3.
AB  - Because polycythemia vera (PV) is a clonal hematopoietic stem cell disease with a
      trilineage hyperplasia, and interleukin-3 (IL-3) stimulates trilineage
      hematopoiesis, we have studied the response of highly purified PV blood burst
      forming units-erythroid (BFU-E) to recombinant human IL-3 (rIL-3). Whereas the
      growth of normal blood BFU-E in vitro rapidly declined by 40 and 60% after 24 and
      48 h of incubation without 50 U/ml of rIL-3, the growth of PV BFU-E declined by
      only 10 and 30% under the same conditions, demonstrating a reduced dependence on
      rIL-3. A reduced dependence of PV BFU-E on recombinant human erythropoietin (rEP)
      was also present. Dose-response experiments showed a 117-fold increase in PV BFU
      E sensitivity to rIL-3, and a 6.5-fold increase in sensitivity to rEP, compared
      to normal BFU-E, whereas blood BFU-E from patients with secondary polycythemia
      responded like normal BFU-E. Endogenous erythroid colony (EEC) formation, which
      is independent of the addition of rEP, was reduced by 50% after erythroid colony
      forming cells were generated from PV BFU-E in vitro without rIL-3 for 3 d,
      whereas rEP-stimulated erythroid colonies were unaffected. These studies
      demonstrate a striking hypersensitivity of PV blood BFU-E to rIL-3, which may be
      the major factor in the pathogenesis of increased erythropoiesis without
      increased EP concentrations.

PMID- 1991826
TI  - Impaired uptake of glutathione by hepatic mitochondria from chronic ethanol-fed
      rats. Tracer kinetic studies in vitro and in vivo and susceptibility to oxidant
      stress.
AB  - Isolated hepatocytes incubated with [35S]-methionine were examined for the time
      dependent accumulation of [35S]-glutathione (GSH) in cytosol and mitochondria,
      the latter confirmed by density gradient purification. In GSH-depleted and 
      repleted hepatocytes, the increase of specific activity of mitochondrial GSH
      lagged behind cytosol, reaching nearly the same specific activity by 1-2 h.
      However, in hepatocytes from ethanol-fed rats, the rate of increase of total GSH
      specific radioactivity in mitochondria was markedly suppressed. In in vivo steady
      state experiments, the mass transport of GSH from cytosol to mitochondria and
      vice versa was 18 nmol/min per g liver, indicating that the half-life of
      mitochondrial GSH was approximately 18 min in controls. The fractional transport
      rate of GSH from cytosol to mitochondria, but not mitochondria to cytosol, was
      significantly reduced in the livers of ethanol-fed rats. Thus, ethanol-fed rats
      exhibit a decreased mitochondrial GSH pool size due to an impaired entry of
      cytosol GSH into mitochondria. Hepatocytes from ethanol-fed rats exhibited a
      greater susceptibility to the oxidant stress-induced cell death from tert
      butylhydroperoxide. Incubation with glutathione monoethyl ester normalized the
      mitochondrial GSH and protected against the increased susceptibility to t
      butylhydroperoxide, which was directly related to the lowered mitochondrial GSH
      pool size in ethanol-fed cells.

PMID- 1991827
TI  - Proglucagon products in plasma of noninsulin-dependent diabetics and nondiabetic
      controls in the fasting state and after oral glucose and intravenous arginine.
AB  - We investigated the major products of proglucagon (PG) processing in plasma in
      the fasting state, after intravenous arginine and after an oral glucose load in
      noninsulin-dependent diabetics (NIDDM) and in weight matched controls using
      specific radioimmunoassays and analytical gel filtration. In the fasting state
      the glucagonlike peptide-1 (GLP-1) immunoreactivity was significantly elevated in
      the NIDDM group compared with the control group. Both after intravenous arginine
      and after an oral glucose load a rise in the plasma concentrations of all
      immunoreactive moieties measured was seen. All integrated incremental responses
      after intravenous arginine were identical in the two groups. After oral glucose
      the insulin concentrations in plasma were lower and the concentrations of all
      proglucagon products were higher in the NIDDM group compared to the control
      group. The gel filtration analysis showed that arginine stimulated the secretion
      of pancreatic glucagon (PG 33-61), major proglucagon fragment (PG 72-158) and
      probably GLP-1 (PG 72-107 amide) in both groups, whereas oral glucose stimulated
      the secretion of glicentin (PG 1-69) and intestinal GLP-1 (PG 78-107 amide), an
      insulinotropic hormone. The elevated levels of immunoreactive GLP-1 in diabetics
      in the fasting state were mainly due to an increased concentration of major
      proglucagon fragment.

PMID- 1991828
TI  - Enhanced activity of the free radical producing enzyme xanthine oxidase in
      hypoxic rat liver. Regulation and pathophysiologic significance.
AB  - It has been widely proposed that conversion of xanthine dehydrogenase (XDH) to
      its free radical-producing form, xanthine oxidase (XOD), underlies
      ischemic/reperfusion injury, although the relationship of this conversion to
      hypoxia and its physiologic control have not been defined. This study details the
      time course and control of this enzymatic interconversion. In a functionally
      intact, isolated perfused rat liver model, mean % XOD activity increased as a
      function of both the duration (25 to 45% in 3 h) and degree (r = 0.97) of
      hypoxia. This process was markedly accelerated in ischemic liver by an overnight
      fast (45 vs. 30% at 2 h), and by imposing a short period of in vivo ischemia
      (cardiopulmonary arrest 72%). Moreover, only under these conditions was there a
      significant rise in the XOD activity due to the conformationally altered XDH
      molecule (XODc, 18%), as well as concomitant morphologic injury. Neither
      circulating white blood cells nor thrombosis appeared to contribute to the
      effects of in vivo ischemia on enzyme conversion. Thus, it is apparent that
      conversion to the free radical-producing state, with high levels of XOD activity
      and concurrent cellular injury, can be achieved during a relatively short period
      of hypoxia under certain well-defined physiologic conditions, in a time course
      consistent with its purported role in modulating reperfusion injury. These data
      also suggest that the premorbid condition of organ donors (e.g., nutritional
      status and relative state of hypoxia) is important in achieving optimal organ
      preservation.

PMID- 1991829
TI  - Advanced glycosylation products quench nitric oxide and mediate defective
      endothelium-dependent vasodilatation in experimental diabetes.
AB  - Nitric oxide (an endothelium-derived relaxing factor) induces smooth muscle
      relaxation and is an important mediator in the regulation of vascular tone.
      Advanced glycosylation end products, the glucose-derived moieties that form
      nonenzymatically and accumulate on long-lived tissue proteins, have been
      implicated in many of the complications of diabetes and normal aging. We
      demonstrate that advanced glycosylation products quench nitric oxide activity in
      vitro and in vivo. Acceleration of the advanced glycosylation process in vivo
      results in a time-dependent impairment in endothelium-dependent relaxation.
      Inhibition of advanced glycosylation with aminoguanidine prevents nitric oxide
      quenching, and ameliorates the vasodilatory impairment. These results implicate
      advanced glycosylation products as important modulators of nitric oxide activity
      and endothelium-dependent relaxation.

PMID- 1991830
TI  - Entrainment of pulsatile insulin secretion by oscillatory glucose infusion.
AB  - Ultradian "oscillations" or "pulses" of insulin secretion with periods around 120
      min occur in man. It is not known whether glucose plays an active role in
      generating these oscillations, or if an intrapancreatic pacemaker generates
      oscillations in insulin secretion that entrain glucose passively. To determine if
      the frequency of pulses of insulin secretion could be modified by oscillatory
      glucose infusion, seven normal men were studied on three separate occasions. The
      first study involved a constant glucose infusion administered at a rate of 6
      mg/kg per min for 28 h. During the two subsequent studies, the subjects received
      an oscillatory glucose infusion for 28 h with the same mean rate, an amplitude of
      33% above and below the mean infusion rate, a sinusoidal waveshape and a period
      either 20% longer ("slow oscillatory infusion") or 20% shorter ("rapid
      oscillatory infusion") than the periodicity observed during constant glucose
      infusion. Samples for insulin, C-peptide, and glucose were drawn at 10-min
      intervals during the last 24 h of each study. Insulin secretion rates were
      calculated by deconvolution of C-peptide levels. During constant glucose
      infusion, the respective periods of oscillation of glucose and insulin secretion
      averaged 126 +/- 5 min and 118 +/- 3 min (mean +/- SEM). During the slow
      oscillatory infusion, the period of infusion was 155 +/- 7 min and the periods of
      insulin secretion and glucose were, respectively, 155 +/- 7 min and 150 +/- 5
      min. During rapid oscillatory infusion, the period of infusion was 103 +/- 5 min
      and the period of both insulin secretion and glucose was 105 +/- 5 min. Thus the
      periodicity of both insulin secretion and plasma glucose changed in parallel with
      the exogenous periodicity, indicating complete entrainment of the secretory
      oscillations. These results suggest that the ultradian oscillations of insulin
      secretion are caused by the feedback loop linking glucose and insulin.

PMID- 1991831
TI  - Recruitment of neutrophils during IgE-dependent cutaneous late phase reactions in
      the mouse is mast cell-dependent. Partial inhibition of the reaction with
      antiserum against tumor necrosis factor-alpha.
AB  - Much of the clinically important pathology associated with IgE-dependent
      disorders is thought to reflect the actions of the blood-borne leukocytes
      recruited during these responses. To evaluate the extent to which mast cells are
      responsible for the leukocyte infiltration associated with IgE-dependent
      cutaneous reactions, we attempted to elicit these responses in normal mice,
      genetically mast cell-deficient W/Wv mice, and in W/Wv mice selectively repaired
      of their mast cell deficiency by the intradermal injection of cultured mast cells
      derived from the congenic normal (+/+) mice. We found that the tissue swelling
      associated with IgE-dependent passive cutaneous anaphylaxis reactions developed
      rapidly and diminished markedly from 2 to 4 h after antigen challenge, but
      remained detectable for at least 24 h after elicitation of the responses.
      Infiltration of leukocytes (predominantly neutrophils) also occurred at these
      sites, but reached maximal levels 6-12 h after antigen challenge, persisted at
      high levels for 24 h, and largely waned by 48 h. Virtually all of the tissue
      swelling and leukocyte infiltration associated with IgE-dependent cutaneous
      reactions was mast cell dependent. Intradermal injection of 40 U of recombinant
      murine TNF-alpha (rmTNF-alpha) elicited neutrophil infiltration similar in
      magnitude and kinetics to that observed after IgE-dependent mast cell
      degranulation. A rabbit anti-rmTNF-alpha (R anti-rmTNF-alpha) antiserum, which
      was able to inhibit 84% of the neutrophil infiltration observed after i.d.
      injection of rmTNF-alpha, inhibited IgE-, and mast cell-dependent leukocyte
      infiltration by 47 +/- 7% in three separate experiments. These findings indicate
      that TNF-alpha contributes to mast cell-dependent recruitment of leukocytes
      during IgE-dependent cutaneous late phase reactions, but suggest that other mast
      cell-associated mediators probably also contribute to this response.

PMID- 1991832
TI  - Supraphysiologic L-tryptophan elicits cytoskeletal and macromolecular
      permeability alterations in hamster small intestinal epithelium in vitro.
AB  - We have previously shown that Na(+)-coupled transport of glucose and amino acids
      across the apical membrane of intestinal absorptive cells is accompanied by
      alterations in cytoskeletal structure and altered sieving of small hydrophilic
      solutes by tight junctions. Here we report that in response to the essential
      amino acid L-tryptophan at lumenal concentrations likely to be supraphysiological
      (1 mM or greater), these responses are so exaggerated as to induce disruption of
      tight junctions and transepithelial macromolecular leaks. Since these effects of
      L-tryptophan are energy and Na+ dependent and occur with mucosal but not serosal
      exposure to L-tryptophan, it appears they are triggered by activation of a Na(+)
      nutrient cotransporter in the apical membrane of absorptive cells rather than by
      the presence of an unidentified trace contaminant. Our findings suggest the
      possibility that dietary supplementation by L-tryptophan may result in loss of
      the intestinal epithelial barrier to dietary antigens. We speculate that such a
      response to supraphysiologic tryptophan may contribute, in part, to the recently
      recognized curious tryptophan-induced eosinophilia myalgia syndrome.

PMID- 1991833
TI  - Macrophages from nephrotic rats regulate apolipoprotein E biosynthesis and
      cholesterol content independently.
AB  - The effects of the nephrotic syndrome in rats on the cholesterol content and the
      biosynthesis of apolipoprotein E (apoE) by resident peritoneal macrophages have
      been investigated. Since the nephrotic syndrome has been associated with an
      increased risk of coronary atherosclerosis, we hypothesized that macrophages from
      nephrotic rats would accumulate cholesterol and undergo transformation into foam
      cells, with a concomitant increase in apoE biosynthesis. The nephrotic syndrome
      was induced in rats with puromycin aminonucleoside. Peritoneal macrophages
      exposed in vivo for 7-21 d to ascites fluid derived from plasma containing
      sixfold elevations of lipoproteins did not accumulate unesterified or esterified
      cholesterol. Nevertheless, immunoprecipitation assays after incubation of the
      isolated cells with [35S]methionine, or immunoblot analysis of the incubation
      medium demonstrated a 2.6-fold increase in apoE secretion compared with normal
      macrophages. This increase was accompanied by 5- to 10-fold increases in cellular
      apoE messenger RNA as determined by quantitative solution hybridization assay.
      Peritoneal macrophages cultured from nephrotic rats during the period of
      hypercholesterolemia also showed distinct and highly reproducible morphologic
      changes. The dissociation between apoE biosynthesis and macrophage cholesterol
      content provides new insight into the response of peritoneal macrophages in vivo
      to endogenous hyperlipemia.

PMID- 1991834
TI  - Screening of nineteen unrelated families with generalized resistance to thyroid
      hormone for known point mutations in the thyroid hormone receptor beta gene and
      the detection of a new mutation.
AB  - Generalized resistance to thyroid hormone (GRTH) is a syndrome characterized by
      impaired tissue responsiveness to thyroid hormone. Two distinct point mutations
      in the hormone binding domain of the thyroid hormone receptor (TR) beta have
      recently been identified in two unrelated families with GRTH. One, Mf, involves a
      replacement of the normal glycine-345 for arginine in exon 7 and another, Mh,
      replaces the normal proline-453 for histidine in exon 8. To probe for the
      presence of the Mf and Mh defect in 19 unrelated families with GRTH, we applied
      separate polymerase chain reactions using allele-specific oligonucleotide primers
      containing the normal and each of the two mutant nucleotides at the 3'-position.
      A total of 24 affected subjects and 13 normal family members were studied. The
      mode of inheritance was dominant in 13 families, was unknown in 5 families, and
      was clearly recessive in 1 family in which only the consanguineous subjects were
      affected. Primers containing the substitutions specific for Mf and Mh amplified
      exons 7 and 8, respectively, only in affected members of each of the two index
      families. Primers containing the normal sequences amplified exons 7 and 8 of the
      TR beta gene in all subjects except affected members of one family. In this
      family with recessively inherited GRTH, neither exon could be amplified using any
      combinations of primers and DNA blot revealed absence of all coding exons. These
      results indicate a major deletion of the TR beta gene, including both DNA and
      hormone binding domains. Since heterozygous members of this family are not
      affected, the presence of a single normal allele is sufficient for normal
      function of the TR beta. These data also support the hypothesis that in the
      dominant mode of GRTH inheritance the presence of an abnormal TR beta interferes
      with the function of the normal TR beta. Distinct mutations are probably
      responsible for GRTH in unrelated families.

PMID- 1991835
TI  - Intravenous administration of phosphorylated acid alpha-glucosidase leads to
      uptake of enzyme in heart and skeletal muscle of mice.
AB  - The lysosomal storage disorder glycogenosis type II is caused by acid alpha
      glucosidase deficiency. In this study we have investigated the possible
      applicability of mannose 6-phosphate receptor-mediated enzyme replacement therapy
      to correct the enzyme deficiency in the most affected tissues. Bovine testes acid
      alpha-glucosidase containing phosphorylated mannose residues was intravenously
      administered to mice and found to be taken up by heart (70% increase of activity)
      and skeletal muscle (43% increase); the major target organs. The uptake of
      nonphosphorylated human placenta acid alpha-glucosidase by heart and skeletal
      muscle appeared to be significantly less efficient, whereas uptake of
      dephosphorylated bovine testes enzyme was not detectable. The phosphorylated
      bovine testes acid alpha-glucosidase remained present in mouse skeletal muscle up
      to 9-15 d after administration, with a half-life of 2-4 d. Besides being measured
      in skeletal muscle and heart, uptake of phosphorylated bovine testes and
      nonphosphorylated human placenta acid alpha-glucosidase was measured in several
      other organs, but not in brain. The increase of acid alpha-glucosidase activity
      was highest in liver and spleen. We concluded that application of mannose 6
      phosphate receptor-mediated enzyme replacement therapy may offer new perspectives
      for treatment of glycogenesis type II.

PMID- 1991836
TI  - Quantitation of G0 and G1 phase cells in primary carcinomas. Antibody to M1
      subunit of ribonucleotide reductase shows G1 phase restriction point block.
AB  - Human cancers have an apparent low growth fraction, the bulk of cells presumed to
      being out of cycle in a G0 quiescent state due to the inability in the past to
      distinguish G0 from G1 cells. The allosteric M1 subunit of ribonucleotide
      reductase (M1-RR) is constitutively expressed by cycling cells (i.e., G1, S, G2
      M). It is acquired during transition from G0 to G1, lost during exit to G0 and
      thus distinguishes G0 from G1 cells. To estimate the proportion of G0 and G1
      cells in primary human breast (n = 5) and colorectal (n = 12) adenocarcinomas, we
      used both analytical DNA flow cytometry (ADFC) and immunoperoxidase staining of
      sections with the monoclonal antibody to M1-RR (MAb M1-RR). ADFC of fresh tumors
      revealed a low percentage of cells in the S phase (4.0 +/- 3.4%) but
      immunoperoxidase staining for M1-RR revealed an unexpectedly high proportion of
      positive cells (52.4 +/- 12.7%) in the G1, S, G2-M phases indicating a high G1
      content of primary human tumors. Thus, human cancers are blocked in transition in
      G1 and are not predominantly in a G0 or quiescent differentiated state. This
      block was interpreted to mean that human cancers are responding to putative
      regulatory events at a restriction point in the G1 phase, such as relative growth
      factor deficiency, density inhibition, antiproliferative cytokines, or gene
      products. Using flow cytometry for both DNA and M1-RR content we found that human
      colon cancer cell lines arrest in the G1 but not G0 phase upon serum deprivation
      or density inhibition. Similarly, human breast cancer cell lines are arrested in
      G1 but not G0 phase by medroxyprogesterone acetate (MPA) or tamoxifen exposure.
      These findings match our in situ observations, and support the concept of a
      restriction point block in primary human tumors.

PMID- 1991837
TI  - Binding of Cryptococcus neoformans by human cultured macrophages. Requirements
      for multiple complement receptors and actin.
AB  - We studied the receptors on human cultured macrophages (MO-M phi) responsible for
      binding encapsulated and isogenic mutant acapsular strains of Cryptococcus
      neoformans, and whether such binding leads to a phagocytic event. Both strains
      required opsonization with complement components in normal human serum in order
      for binding to occur. Binding of the acapsular, but not the encapsulated, strain
      led to phagocytosis. MAb directed against any of the three defined complement
      receptors (CR) on MO-M phi (CR1, CR3, and CR4) profoundly inhibited binding of
      serum-opsonized encapsulated (and to a lesser extent acapsular) organisms to MO-M
      phi. Immunofluorescence studies demonstrated migration of CR to the area of the
      cryptococcal binding site. Trypsin and elastase inhibited binding of encapsulated
      and, to a lesser extent, acapsular yeasts to MO-M phi. Binding of encapsulated C.
      neoformans was profoundly inhibited by incubation in the cold or by inhibitors of
      receptor capping and actin microfilaments. Thus, multiple CR appear to contribute
      to binding of serum-opsonized encapsulated C. neoformans by MO-M phi. Binding is
      an energy-dependent process that requires conformational changes in actin yet
      does not lead to phagocytosis of the organism. In contrast, energy is not
      required for binding of acapsular yeasts by MO-M phi and binding triggers
      phagocytosis.

PMID- 1991838
TI  - Myocardial protein turnover in patients with coronary artery disease. Effect of
      branched chain amino acid infusion.
AB  - The regulation of protein metabolism in the human heart has not previously been
      studied. In 10 postabsorptive patients with coronary artery disease, heart
      protein synthesis and degradation were estimated simultaneously from the
      extraction of intravenously infused L-[ring-2,6-3H]phenylalanine (PHE) and the
      dilution of its specific activity across the heart at isotopic steady state. We
      subsequently examined the effect of branched chain amino acid (BCAA) infusion on
      heart protein turnover and on the myocardial balance of amino acids and branched
      chain ketoacids (BCKA) in these patients. In the postabsorptive state, there was
      a net release of phenylalanine (arterial-cardiac venous [PHE] = -1.71 +/- 0.32
      nmol/ml, P less than 0.001; balance = -116 +/- 21 nmol PHE/min, P less than
      0.001), reflecting protein degradation (142 +/- 40 nmol PHE/min) in excess of
      synthesis (24 +/- 42 nmol PHE/min) and net myocardial protein catabolism. During
      BCAA infusion, protein synthesis increased to equal the degradation rate (106 +/-
      24 and 106 +/- 28 nmol PHE/min, respectively) and the phenylalanine balance
      shifted (P = 0.01) from negative to neutral (arterial-cardiac venous [PHE] = 0.07
      +/- 0.36 nmol/ml; balance = 2 +/- 25 nmol PHE/min). BCAA infusion stimulated the
      myocardial uptake of both BCAA (P less than 0.005) and their ketoacid conjugates
      (P less than 0.001) in proportion to their circulating concentrations. Net uptake
      of the BCAA greatly exceeded that of other essential amino acids suggesting a
      role for BCAA and BCKA as metabolic fuels. Plasma insulin levels, cardiac double
      product, coronary blood flow, and myocardial oxygen consumption were unchanged.
      These results demonstrate that the myocardium of postabsorptive humans is in
      negative protein balance and indicate a primary anabolic effect of BCAA on the
      human heart.

PMID- 1991839
TI  - Normalization of blood glucose in diabetic rats with phlorizin treatment reverses
      insulin-resistant glucose transport in adipose cells without restoring glucose
      transporter gene expression.
AB  - Evidence is emerging for a direct role of glucose, independent of changes in
      insulin, in the regulation of cellular glucose transport and glucose utilization
      in vivo. In this study we investigate potential cellular and molecular mechanisms
      for this regulatory effect of glucose by determining how normalization of
      glycemia without insulin therapy in diabetic rats influences 3-O-methylglucose
      transport and the expression and translocation of two genetically distinct
      species of glucose transporters (GTs) in adipose cells. These results are
      compared with alterations in glucose disposal in vivo measured by euglycemic
      clamp. In rats rendered diabetic by 90% pancreatectomy, insulin-stimulated
      glucose transport in adipose cells is decreased 50% in parallel with reduced
      insulin-mediated glucose disposal in vivo. Levels of adipose/muscle GTs measured
      by immunoblotting are decreased in adipose cell subcellular membrane fractions,
      as are the corresponding mRNA levels assessed by Northern blotting of total
      adipose cell RNA. Normalization of blood glucose in diabetic rats with phlorizin,
      which impairs renal tubular glucose reabsorption and thus enhances glucose
      excretion, restores insulin-stimulated glucose transport in adipose cells and
      insulin-mediated glucose disposal in vivo. Importantly, levels of the
      adipose/muscle GT protein remain 43% reduced in the low-density microsomes in the
      basal state and 46% reduced in the plasma membranes in the insulin-stimulated
      state. Adipose/muscle GT mRNA levels remain approximately 50% depressed. Levels
      of the HepG2/brain GT protein and mRNA are unaltered by diabetes or phlorizin
      treatment. Thus, changes in ambient glucose independent of changes in ambient
      insulin can regulate the glucose transport response to insulin in isolated
      adipose cells and changes in responsiveness parallel alterations in glucose
      uptake in vivo. Since this effect can occur without alteration in the expression
      of the two species of glucose transporters present in adipose cells or in their
      translocation to the plasma membrane in response to insulin, it may result from
      changes in GT functional activity.

PMID- 1991840
TI  - Enhancement of platelet reactivity and modulation of eicosanoid production by
      intact erythrocytes. A new approach to platelet activation and recruitment.
AB  - Erythrocytes are known to influence hemostasis. Bleeding times are prolonged in
      anemia and corrected by normalizing the hematocrit. We now demonstrate that
      intact erythrocytes modulate biochemical and functional responsiveness of
      activated platelets. A two-stage procedure, permitting studies of cell-cell
      interactions and independently evaluating platelet activation and recruitment
      within 1 min of stimulation, was developed. Erythrocytes increased platelet
      serotonin release despite aspirin treatment, enzymatic adenosine diphosphate
      removal, protease inhibition, or combinations thereof. The data suggested that
      erythrocyte enhancement of platelet reactivity can reduce the therapeutic
      effectiveness of aspirin. Erythrocytes metabolically modified platelet
      arachidonate or eicosapentaenoate release and eicosanoid formation. They promoted
      significant increases in cyclooxygenase and lipoxygenase metabolites upon
      platelet stimulation with collagen or thrombin. However, with ionophore,
      erythrocytes strongly reduced platelet lipoxygenation. These erythrocyte
      modulatory effects were stimulus-specific. Activated platelet-erythrocyte
      mixtures, with or without aspirin, promoted 3-10-fold increases in extracellular
      free fatty acid, which would be available for transcellular metabolism.
      Erythrocyte-induced increases in free eicosapentaenoate may contribute to
      antithrombotic and anti-inflammatory effects of this fish oil derivative. These
      results provide biochemical insight into erythrocyte contributions to thrombosis
      and hemostasis, and support the concept of thrombus formation as a multicellular
      event.

PMID- 1991842
TI  - Influence of age on the metabolism of plasma low density lipoproteins in healthy
      males.
AB  - The plasma concentration of the atherogenic low density lipoproteins (LDL)
      increases with age. To clarify the mechanism of this change, we studied the
      kinetics of autologous 125I-LDL apolipoprotein B (apo B) in 41 normolipidemic,
      nonobese healthy males. For comparison, they were divided into three age groups:
      young, 21-39 yr (n = 18), middle-aged, 40-59 yr (n = 11), and old, 60-80 yr (n =
      12). The levels of plasma LDL cholesterol and LDL apo B increased from
      respectively 3.4 +/- 0.1 (SEM) mmol/liter and 86 +/- 2 mg/dl in the young to 4.1
      +/- 0.1 mmol/liter and 95 +/- 3 mg/dl in the old (P less than 0.01), and this
      increase was linked to a progressively decreased (r = -0.38, P less than 0.02)
      fractional catabolic rate of LDL apo B (0.348 +/- 0.010 pools per day in the
      young vs. 0.296 +/- 0.009 pools per day in the old, P less than 0.01). The
      production rate of LDL apo B did not differ significantly between the groups. The
      reduced fractional catabolic rate of LDL apo B in the old was not associated with
      a decrease in binding affinity of the LDL particle to its receptor, as judged
      from its ability to compete for 125I-LDL fibroblast binding. When hepatic LDL
      receptor expression was stimulated by cholestyramine treatment in six old males,
      their LDL apo B fractional catabolic rate increased to the levels observed in the
      young subjects. We conclude that the increase in LDL which normally occurs with
      age is explained by a reduced capacity for its removal, and hypothesize that this
      is mediated via a reduced hepatic LDL receptor expression.

PMID- 1991841
TI  - Role of increased cytosolic free calcium in the pathogenesis of rabbit proximal
      tubule cell injury and protection by glycine or acidosis.
AB  - To assess the role of increased cytosolic free calcium (Caf) in the pathogenesis
      of acute proximal tubule cell injury and the protection afforded by exposure to
      reduced medium pH or treatment with glycine, fura-2-loaded tubules were studied
      in suspension and singly in a superfusion system. The Ca2+ ionophore, ionomycin,
      increased Caf to micromolar levels and rapidly produced lethal cell injury as
      indicated by loss of lactate dehydrogenase to the medium by suspended tubules and
      accelerated leak of fura and failure to exclude Trypan blue by superfused
      tubules. Decreasing medium Ca2+ to 100 nM prevented the ionomycin-induced
      increases of Caf and the injury. Reducing medium pH from 7.4 to 6.9 or adding 2
      mM glycine to the medium also prevented the cell death, but did not prevent the
      increase of Caf to micromolar levels. Cells treated with 1799, an uncoupler of
      oxidative phosphorylation which produced severe adenosine triphosphate (ATP)
      depletion, did not develop increases of Caf until just before loss of viability.
      Preventing these increases of Caf with 100 nM Ca2+ medium did not protect 1799
      treated cells. Reduced pH and glycine protected 1799-treated cells without
      ameliorating the increases of Caf. These data demonstrate the toxic potential of
      increased Caf in the proximal tubule and show that Caf does sharply increase
      prior to loss of viability in an ATP depletion model of injury, but this increase
      does not necessarily contribute to the outcome. The potent protective actions of
      decreased pH and glycine allow the cells to sustain increases of Caf to
      micromolar levels in spite of severe, accompanying cellular ATP depletion without
      developing lethal cell injury.

PMID- 1991843
TI  - Preservation of the endogenous antioxidants in low density lipoprotein by
      ascorbate but not probucol during oxidative modification.
AB  - Several lines of evidence indicate that the oxidative modification of low density
      lipoproteins (LDL) may provide an important link between plasma LDL and the
      genesis of the atherosclerotic lesion. Ascorbate is an important water-soluble,
      chain-breaking antioxidant in humans. Probucol, a lipid-soluble antioxidant drug
      has been shown to retard the progression of atherosclerosis. The aim of the
      present study was to compare the effects of probucol and physiologic levels of
      ascorbate on the oxidative modification of LDL in both a cell-free (2.5 microM
      Cu++ in phosphate-buffered saline) and cellular system (human monocyte
      macrophages in Ham's F-10 medium). Both ascorbate and probucol inhibited the
      oxidative modification of LDL in both systems to a similar degree as evidenced by
      the thiobarbituric acid-reacting substance activity, electrophoretic mobility,
      and degradation by macrophages. However, whereas co-incubation with physiologic
      levels of ascorbate resulted in a substantial preservation of the alpha
      tocopherol, gamma-tocopherol, and beta-carotene of the LDL, probucol in
      concentrations ranging from 10 to 80 microM failed to protect these antioxidants.
      Thus, in addition to being as potent as probucol in inhibiting the oxidation of
      LDL, ascorbate in contrast preserves the endogenous antioxidants in the LDL.

PMID- 1991844
TI  - Chemotactic factors regulate lectin adhesion molecule 1 (LECAM-1)-dependent
      neutrophil adhesion to cytokine-stimulated endothelial cells in vitro.
AB  - Monoclonal antibodies recognizing CD18, CD11a, CD11b, and neutrophil lectin
      adhesion molecule 1 (LECAM-1), i.e., the human homologue of the murine MEL-14
      antigen, were used to assess the relative contribution of these glycoproteins to
      neutrophil-endothelial adhesion. Under static conditions, the adhesion of
      neutrophils to IL-1-stimulated human umbilical vein endothelial cell (HUVEC)
      monolayers was inhibited by antibodies to CD18, CD11a, and the neutrophil LECAM
      1, and the effect of combining anti-LECAM-1 and anti-CD11a was almost additive.
      Under flow at a wall shear stress 1.85 dyn/cm2, a condition where CD18-dependent
      adhesion is minimal, anti-LECAM-1 inhibited adhesion by greater than 50%.
      Chemotactic stimulation of neutrophils induced a rapid loss of LECAM-1 from the
      neutrophil surface, and the level of neutrophil surface LECAM-1 was closely
      correlated with adhesion under flow. Neutrophils contacting the activated
      endothelial cells for 30 min lost much of their surface LECAM-1, a phenomenon
      induced by a soluble factor or factors released into the medium by the stimulated
      monolayers, and a high percentage migrated through the HUVEC monolayer. This
      migration was almost completely inhibited by anti-CD18, but was unaffected by
      antibodies to neutrophil LECAM-1. These results support the concept that LECAM-1
      is a neutrophil adhesion molecule that participates in the adherence of
      unstimulated neutrophils to cytokine-stimulated endothelial cells under
      conditions of flow, and is then lost from the neutrophil surface coincident with
      the engagement of CD18-dependent mechanisms leading to transendothelial
      migration.

PMID- 1991845
TI  - Murine mast cells synthesize basement membrane components. A potential role in
      early fibrosis.
AB  - Mast cells are resident in tissues, particularly in association with endothelial
      and epithelial cell basement membranes, and increase at sites of inflammation,
      injury, and fibrosis. Although mast cells are known to both release and generate
      proinflammatory molecules in response to inflammatory stimuli, little is known
      about their normal biologic function. Here we demonstrate that IL-3-dependent
      mouse PT18 mast cells, mouse bone marrow-derived mast cells, and rat basophilic
      leukemia cells express large amounts of mRNA for collagen IV, laminin, and
      heparan sulfate proteoglycan. Western blot analysis confirmed that mast cells
      synthesize and secrete significant amounts collagen IV and laminin B1 and B2
      chains. These data suggest that mast cells may contribute to normal tissue repair
      and/or the early overproduction of basement membrane components seen in a variety
      of fibrotic conditions.

PMID- 1991846
TI  - Mutations in the K-ras oncogene induced by 1,2-dimethylhydrazine in preneoplastic
      and neoplastic rat colonic mucosa.
AB  - These experiments were conducted to determine whether point mutations activating
      K-ras or H-ras oncogenes, induced by the procarcinogen 1,2-dimethylhydrazine
      (DMH), were detectable in preneoplastic or neoplastic rat colonic mucosa. Rats
      were injected weekly with diluent or DMH at 20 mg/kg body wt for 5, 10, 15, or 25
      wk, killed, and their colons dissected. DNA was extracted from diluent-injected
      control animals, histologically normal colonic mucosa from carcinogen-treated
      animals, and from carcinomas. Ras mutations were characterized by differential
      hybridization using allele-specific oligonucleotide probes to polymerase chain
      reaction--amplified DNA, and confirmed by DNA sequencing. While no H-ras
      mutations were detectable in any group, K-ras (G to A) mutations were found in
      66% of DMH-induced colon carcinomas. These mutations were at the second
      nucleotide of codons 12 or 13 or the first nucleotide of codon 59 of the K-ras
      gene. The same type of K-ras mutations were observed in premalignant colonic
      mucosa from 2 out of 11 rats as early as 15 wk after beginning carcinogen
      injections when no dysplasia, adenomas, or carcinomas were histologically
      evident, suggesting that ras mutation may be an early event in colon
      carcinogenesis.

PMID- 1991847
TI  - Delivery dependence of early proximal bicarbonate reabsorption in the rat in
      respiratory acidosis and alkalosis.
AB  - In the intact rat kidney, bicarbonate reabsorption in the early proximal tubule
      (EP) is strongly dependent on delivery. Independent of delivery, metabolic
      acidosis stimulates EP bicarbonate reabsorption. In this study, we investigated
      whether systemic pH changes induced by acute or chronic respiratory acid-base
      disorders also affect EP HCO3- reabsorption, independent of delivery (FLHCO3,
      filtered load of bicarbonate). Hypercapnia was induced in rats acutely (1-3 h)
      and chronically (4-5 d) by increasing inspired PCO2. Hypocapnia was induced
      acutely (1-3 h) by mechanical hyperventilation, and chronically (4-5 d) using
      hypoxemia to stimulate ventilation. When compared with normocapneic rats with
      similar FLHCO3, no stimulation of EP or overall proximal HCO3 reabsorption was
      found with either acute hypercapnia (PaCO2 = 74 mmHg, pH = 7.23) or chronic
      hypercapnia (PaCO2 = 84 mmHg, pH = 7.31). Acute hypocapnia (PaCO2 = 29 mmHg, pH =
      7.56) did not suppress EP or overall HCO3 reabsorption. Chronic hypocapnia (PaCO2
      = 26 mmHg, pH = 7.54) reduced proximal HCO3 reabsorption, but this effect was
      reversed when FLHCO3 was increased to levels comparable to euvolemic normocapneic
      rats. Thus, when delivery is accounted for, we could find no additional
      stimulation of proximal bicarbonate reabsorption in respiratory acidosis and,
      except at low delivery rates, no reduction in bicarbonate reabsorption in
      respiratory alkalosis.

PMID- 1991848
TI  - Hypoxia-induced in vivo sickling of transgenic mouse red cells.
AB  - To develop an animal model for sickle cell anemia, we have created transgenic
      mice that express a severe naturally occurring human sickling hemoglobin, Hb S
      Antilles. Due to its low solubility and oxygen affinity, Hb S Antilles has a
      greater propensity to cause red cell sickling than Hb S. To make transgenic
      animals that express a high level of Hb S Antilles, the erythroid-specific DNAse
      I hypersensitive site II from the human beta-globin cluster was linked
      independently to the human alpha 2-globin gene and to the beta S Antilles gene.
      Embryos were injected with both constructs simultaneously and seven transgenic
      mice were obtained, three of which contained both the human alpha and the human
      beta S Antilles transgene. After crossing the human transgenes into the mouse
      beta-thalassemic background a transgenic mouse line was derived in which
      approximately half the beta-globin chains in the murine red cells were human beta
      S Antilles. Deoxygenation of the transgenic red cells in vitro resulted in
      extensive sickling. An increase of in vivo sickling was achieved by placing these
      transgenic mice in a low oxygen environment. This murine model for red cell
      sickling should help to advance our understanding of sickle cell disease and may
      provide a model to test therapeutic interventions.

PMID- 1991849
TI  - Insulin-like growth factor II-mediated proliferation of human neuroblastoma.
AB  - Neuroblastoma is an embryonal tumor that typically arises in cells of the
      developing adrenal medulla. IGF-II mRNA is expressed at high levels in the
      adrenal cortex before birth but it is not detectable until after birth in the
      adrenal medulla. Neuroblastoma cell lines corresponding to early adrenal
      medullary precursors did not express IGF-II, although all three cell lines we
      tested were growth stimulated by IGF-II. Cell lines corresponding to more mature
      adrenal medullary cells expressed IGF-II, and one, SK-N-AS, grows by an IGF-II
      autocrine mechanism (J. Clin. Invest. 84:829-839) El-Badry, Romanus, Helman,
      Cooper, Rechler, and Israel. 1989. An examination of human neuroblastoma tumor
      tissues for IGF-II gene expression using in situ hybridization histochemistry
      revealed that IGF-II is expressed by tumor cells in only 5 of 21 neuroblastomas,
      but is detectable in cells of nonmalignant tissues including adrenal cortical
      cells, stromal fibroblasts, and eosinophils in all 21 tumors. These findings
      indicate that IGF-II may function as an autocrine growth factor for some
      neuroblastomas and as a paracrine growth factor for others. They suggest that the
      growth regulatory pathways utilized by neuroblastoma mimic those used in the
      precursor cell type from which individual tumors arise.

PMID- 1991850
TI  - Limited B cell repertoire in severe combined immunodeficient mice engrafted with
      peripheral blood mononuclear cells derived from immunodeficient or normal humans.
AB  - The ability to engraft human PBMC or fetal tissue immune cells in the severe
      combined immunodeficient (SCID) mouse has created a need for characterization of
      these systems and their application to disease models. We demonstrate that SCID
      mice reconstituted with PBMC support the growth and differentiation of a
      restricted set of B cells. Human IgG levels of 1-2 mg/ml (10-20% of normal human
      serum levels) were routinely achieved in spite of a serum half life of only 12 d.
      Ig levels peaked around 50 d and Ig production was maintained for greater than
      100 d. The Ig was greater than 85% IgG though some IgM, IgA, IgD, and even IgE
      could be detected. However, the human IgG produced in hu-PBL-SCID mice was pauci
      clonal when analyzed by isoelectric focusing and by kappa/lambda light chain
      usage. Using a new polymerase chain reaction based analysis capable of monitoring
      individual VH family utilization, we found that the engrafted B cells showed
      skewed and restricted human VH subfamily utilization. These parameters were
      markedly variable among hu-PBL-SCID mice reconstituted from the same donor cell
      population at both early (21-50 d) and late stages (greater than 100 d). Hu
      PBL/CVI-SCID mice constructed with cells from patients with common variable
      immunodeficiency with an in vitro block in terminal B cell differentiation
      produced human Ig responses that were quantitatively the same as those produced
      by hu-PBL-SCID mice from normal donors. The hu-PBL-SCID system using PBMC appears
      to lead to growth and Ig production by a small number of B cells and results in a
      restricted B cell repertoire.

PMID- 1991851
TI  - Recombinative events of the T cell antigen receptor delta gene in peripheral T
      cell lymphomas.
AB  - Recombinative events of the T cell antigen receptor (TCR) delta-chain gene were
      studied in 37 cases of peripheral T cell lymphoma (PTCL) and related to their
      clinical presentation and the expression of the alpha beta or gamma delta
      heterodimers as determined by immunostaining of frozen tissue samples. There were
      22 cases of alpha beta, 5 cases of gamma delta, and 10 cases of silent TCR
      expressing neither the alpha beta nor gamma delta TCR. 5 different probes were
      used to examine the delta locus. The 22 cases of alpha beta PTCL displayed
      biallelic and monoallelic deletions; a monoallelic V delta 1 J delta 1
      rearrangement was observed in 1 case and a monoallelic germ line configuration in
      7 cases. The 5 cases of gamma delta PTCL displayed biallelic rearrangements: the
      productive rearrangements could be ascribed to V delta 1J delta 1 joining in 3
      cases and VJ delta 1 joining in 2 cases according to the combined pattern of DNA
      hybridization with the appropriate probes and of cell reactivity with the TCR
      delta-1, delta TCS-1, and anti-V delta 2 monoclonal antibodies. In the VJ delta 1
      joining, the rearranged V segments were located between V delta 1 and V delta 2.
      Interestingly, in the third group of 10 cases of silent PTCL, 5 cases were found
      to have a TCR gene configuration identical to that in the TCR alpha beta PTCL, as
      demonstrated by biallelic delta gene deletion. These 5 cases were CD3 positive.
      The 5 remaining cases showed a monoallelic delta gene rearrangement with a
      monoallelic germ line configuration in 4 and a monoallelic deletion in 1. Four of
      these cases were CD3 negative, which was consistent with an immature genotype the
      TCR commitent of which could not be ascertained. Finally, TCR gamma delta PTCL
      consisted of a distinct clinical morphological and molecular entity whereas TCR
      alpha beta and silent PTCL had a similar presentation.

PMID- 1991852
TI  - Role of mast cells in ion transport abnormalities associated with intestinal
      anaphylaxis. Correction of the diminished secretory response in genetically mast
      cell-deficient W/Wv mice by bone marrow transplantation.
AB  - To investigate the role of mast cells in transport abnormalities during
      intestinal anaphylaxis, we examined responses to antigen in isolated intestinal
      preparations from ovalbumin-sensitized genetically mast cell-deficient WBB6F1
      W/Wv (W/Wv) mice and congenic normal WBBGF1(-)+/+ (+/+) mice. Changes in ion
      transport (primarily secretion of chloride ions) were indicated by increases in
      short-circuit current (Isc). In tissues from +/+ mice, antigen caused increases
      in Isc which were significantly inhibited by antagonists to histamine
      (diphenhydramine) and serotonin (ketanserin), by a cyclooxygenase inhibitor
      (piroxicam) and by a neurotoxin (tetrodotoxin). In preparations from W/Wv mice,
      antigen-stimulated responses were approximately 30% of that in +/+ mice and were
      inhibited only by piroxicam. Responses to electrical transmural stimulation of
      nerves were approximately 50% in W/Wv versus +/+ mice, and were inhibited by
      antagonists of mast cell mediators in +/+ but not W/Wv mice. Reconstitution of
      mast cells in W/Wv mice by intravenous injection of +/+ bone marrow cells
      restored the normal responses to both antigen and nerve stimulation. Our results
      indicate that mast cell-dependent mechanisms are primarily responsible for the
      ion secretion associated with intestinal anaphylaxis, but that other cells are
      also involved. In addition, our data provide evidence for the functional
      importance of bidirectional communication between nerves and mast cells in the
      regulation of ion transport in the gastrointestinal tract.

PMID- 1991853
TI  - Growth factor-induced acceleration of tissue repair through direct and inductive
      activities in a rabbit dermal ulcer model.
AB  - The roles of polypeptide growth factors in promoting wound healing and in
      directing the specificity and sequence of responses of different tissues in
      wounds are little understood. We investigated the influence of four growth
      factors on the rates of healing of a novel full thickness dermal ulcer placed on
      an avascular base in the rabbit ear. The wound model precludes significant wound
      contraction and requires new granulation tissue and epithelial cells for healing
      to originate centripetally. 5 micrograms (7-31 pmol/mm2) of platelet-derived
      growth factor-B chain (PDGF-BB), basic fibroblast growth factor (bFGF), and
      epidermal growth factor (EGF) applied locally at the time of wounding resulted in
      a twofold increase in complete reepithelialization of treated wounds (PDGF-BB, P
      = 0.02 chi square analysis; bFGF, P = 0.04; EGF, P = 0.05); transforming growth
      factor (TGF)-beta 1 significantly inhibited reepithelialization (P = 0.05). Both
      PDGF-BB and TGF-beta 1 uniquely increased the depth and area of new granulation
      tissue (P less than 0.005), the influx of fibroblasts, and the deposition of new
      matrix into wounds. Explants from 7-d old PDGF-BB-treated wounds remained
      metabolically far more active than controls, incorporating 473% more
      [3H]thymidine into DNA (P = 0.05) and significantly more [3H]leucine and
      [3H]proline into collagenase-sensitive protein (P = 0.04). The results establish
      that polypeptide growth factors have significant and selective positive
      influences on healing of full thickness ulcers in the rabbit.

PMID- 1991855
TI  - Mechanism of intestinal secretion. Effect of serotonin on rabbit ileal crypt and
      villus cells.
AB  - To determine the mechanism of action of an intestinal secretagogue, serotonin, we
      have isolated crypt and villus cells and demonstrated Na:H and Cl:HCO3 exchange
      activity using the intracellular pH-sensitive fluorescent dye, 2,7-bis (carboxy
      ethyl)-5,6-carboxy-fluorescein. Serotonin alkalinized both crypt and villus
      cells. Alkalinization in villus cells was HCO3 dependent and Na independent. In
      contrast, alkalinization in crypt cells was HCO3 independent and Na dependent. In
      villus cells, recovery from an alkaline load induced by Cl removal, 4,4'
      diisothiocyanatostilbene-2,2'-disulfonic acid or propionate pulse, known to occur
      via the Cl:HCO3 exchange, is inhibited by serotonin. In contrast, in crypt cells,
      recovery from an acid load induced by Na removal, amiloride and NH4Cl pulse,
      known to occur via Na:H exchange, is stimulated by serotonin. These data suggest
      that serotonin is inhibiting Cl:HCO3 exchange in villus cells and stimulating
      Na:H exchange in crypt cells. These effects of serotonin would be expected to
      inhibit coupled Na and Cl absorption by villus cells and stimulate HCO3 secretion
      by crypt cells in the intact ileum.

PMID- 1991854
TI  - No evidence for serological autoimmunity to islet cell heat shock proteins in
      insulin dependent diabetes.
AB  - Recent studies in nonobese diabetic mice have implicated the autoimmune
      destruction of pancreatic islet cells with immunity to a beta cell protein cross
      reactive to Mycobacterium tuberculosis heat shock protein 65 (hsp 65). Therefore,
      our studies examined serological immunity to islet cell hsp in humans with
      insulin-dependent diabetes (IDD). Heat shock of human islet cells in vitro
      markedly increased the synthesis of proteins of 72,000, 75,000, and 90,000 Mr. No
      autoantibodies reactive to these hsp, nor to the constituently expressed islet
      cell hsp 65 protein (identified as 60,000 Mr) were observed in IDD patients. The
      islet cell 64,000-Mr autoantigen and hsp 65 proteins were physiologically and
      immunocompetitively distinct. These experiments do not support the hypothesis
      that IDD in humans is associated with autoimmunity to islet cell heat shock
      proteins.

PMID- 1991856
TI  - Video microscope observations of human premolar eruption.
AB  - It is now possible to observe with an accuracy of 1-2 microns the pattern of
      eruptive movements of a human premolar as it moves from gingival emergence to the
      occlusal plane. This was accomplished by use of a video microscope to track the
      position of an optical ruling on the erupting tooth relative to a reference
      ruling mounted on adjacent teeth that were in occlusion. Net eruptive movements
      averaging 25-75 microns occurred from one day to the next until the tooth was
      almost in occlusion; then the eruptive rate slowed. Eruption occurred almost
      entirely at night. During the day, there was a marked slowing or cessation of
      eruption and often intrusion, which appeared to be related to masticatory
      activity.

PMID- 1991857
TI  - A review of quantitative methods for studies of mineral content of intra-oral
      caries lesions.
AB  - Modern prospective caries studies require the measurement of small changes in
      tooth mineral content. Quantitative measurements of changes in mineral content in
      a single caries lesion is desirable. Quantitative methods can be either
      destructive or non-destructive. The latter type permits longitudinal studies to
      be conducted. Various methods available for the analysis of lesion parameters are
      reviewed. The basic principle of each method is summarized, and its
      characteristics are discussed. For each method, the correlation between the
      measured parameter and mineral loss, the useful range of mineral loss, the
      discrimination threshold, and the repeatability, are presented. Where such
      quantities were not available in the original papers, they were calculated from
      literature data. A comprehensive table of specifications of all methods is given.

PMID- 1991858
TI  - Involvement of PGE synthesis in the effect of intermittent pressure and
      interleukin-1 beta on bone resorption.
AB  - Human periodontal ligament (PDL) fibroblasts, cultured from extracted healthy
      premolars, and a cloned osteogenic cell line (MC3T3-E1) were used in this study
      to determine the effect of intermittent pressure on bone resorption. Cells (1 x
      10(5] were incubated with BGJb medium in the presence or absence of the following
      factors: intermittent negative (-30 g/cm2) or positive (30 g/cm2) hydrostatic
      pressure and interleukin-1 beta (IL-1 beta, 1 ng/mL), for 24 h. Conditioned media
      (CM) generated from cultures of either cell types were used for prostaglandin E
      (PGE) assay, bone resorption assay, and assessment of osteoclast (OC)-like cell
      formation. Unstimulated PDL fibroblasts or MC3T3-E1 cells produced measurable
      amounts of PGE and bone-resorbing activity as measured by 45Ca released from
      mouse calvaria and OC-like cells. IL-1 beta-treated cells showed significantly
      elevated levels of PGE, bone resorption, and OC-like cell formation, as compared
      with unstimulated cells. Intermittent positive pressure (IPP) alone stimulated
      PGE production, but the resultant CM did not stimulate bone resorption or OC-like
      cell formation when IPP was applied to either cell type. The application of IPP,
      together with IL-1 beta in CM, caused a slight increase in the number of alpha
      like cells, as compared with that of IL-1 beta-treated CM in both cell types. On
      the other hand, direct application of IPP on mouse bone-marrow cultures
      significantly increased the number of OC-like cells. This effect was additive in
      combination with either CM from unstimulated cells or exogenous addition of
      PGE2.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1991859
TI  - Enhancing the virulence of Streptococcus sobrinus in rats.
AB  - The purpose of this study was to explore the virulence of strains of
      Streptococcus sobrinus that had been re-isolated from a desalivated rat.
      Furthermore, we wished to determine the influence of desalivation on the
      acidogenicity of fasting and sucrose-pulsed dental plaque in rats infected by
      strains of S. sorbrinus. Experimental groups were formed and infected as follows:
      Group 1, desalivated animals, S. sorbrinus ATCC27352; Group 2, intact animals,
      infected as in Group 1; Group 3, desalivated animals, S. sorbrinus re-isolated
      from a desalivated animal that had been infected with the ATCC 27352 strain for
      five weeks; Group 4, intact animals, infected as in Group 3; Group 5, desalivated
      animals, S. sobrinus re-isolated from a desalivated animal that had been infected
      with the ATCC27352 strain for ten weeks; Group 6, intact animals, infected as in
      Group 5; Group 7, intact animals, no infection. All animals were fed cariogenic
      diet 2000 and sucrose-sweetened drinking water ad libitum. After five weeks,
      desalivated and intact animals that had been infected with isolates obtained from
      desalivated animals had significantly higher (p less than 0.05) smooth-surface
      caries scores than did intact and desalivated animals infected with cultures of
      the original stock ATCC strain. Moreover, fasting plaque pH values were
      statistically lower in desalivated animals (Groups 1 and 3) than in intact
      animals (Groups 2, 6, and 7) (Turkey analysis, p less than 0.05).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1991860
TI  - Detection of periodontal disease activity with a scintillation camera.
AB  - The goal of this study was to assess the ability of a scintillation camera method
      to detect areas of active bone loss due to periodontitis. Technetium 99m
      methylene diphosphonate was used as the bone-seeking radiopharmaceutical. Bone
      seeking radiopharmaceutical uptake (BSRU) was imaged and quantified in alveolar
      bone regions of interest with a scintillation camera and a computer. Analysis of
      the sequential radiographs over six months constituted the basis for
      determination of sites of active disease. The study was composed of two parts.
      First, 18 subjects, nine with adult periodontitis and nine controls, were
      enrolled in a cross-sectional study to determine whether the quantitative
      scintillation amera methodology detected differences in BSRU in periodontitis vs.
      periodontally healthy patients. Second, the nine patients with periodontitis were
      studied longitudinally in order to determine whether the BSRU examination was
      indicative of bone loss subsequently measured radiographically. In the cross
      sectional study, the mean uptake ratio for the periodontitis group was
      significantly higher than that for the control group (1.63 +/- 0.06 and 1.42 +/-
      0.04, respectively, p less than 0.01, t test). From the longitudinal study, the
      mean patient scintillation image uptake ratios were highly correlated with the
      mean bone loss determined from serial radiographs (p less than 0.01). The
      accuracy, sensitivity, and specificity of the quantitative gamma camera method
      for detecting site(s) of active bone loss within the region of interest were
      assessed relative to the longitudinal radiographic data. The accuracy,
      sensitivity, and specificity were 85%, 90%, and 79%, respectively. Alveolar bone
      scintigraphy with a gamma camera and computer may provide a simple and valid
      technique for the immediate indication of areas of periodontal disease activity.

PMID- 1991861
TI  - Microleakage of three cement bases.
AB  - The purpose of this study was to evaluate the ability of a glass-ionomer cement
      base material to prevent bacterial penetration along the dentin interface and to
      compare it with two conventional cement-base materials. A total of 107 Class 5
      restorations was placed in Rhesus monkey teeth by means of three test materials
      [zinc oxide-eugenol (ZOE), copalite varnish + zinc phosphate cement base (V +
      ZP), and a glass-ionomer lining cement (GI)], with unetched and unbonded resin
      composite used alone as a control material and as a final restoration over the
      test base materials. Following disinfection, Class 5 cavities were prepared on
      the buccal surfaces of the teeth to the inner one-half of dentin. A sterile
      filter-paper disk was then placed on the axial wall and covered with a Teflon
      disk. Next, the cavities were based to the dento-enamel junction with one of the
      test base materials and finally restored with unetched and unbonded resin
      composite. After five and 16 weeks, the filter-paper disks were retrieved and
      cultivated for the presence and type of bacteria. The five-week results showed
      positive growth in two groups: the composite-only controls and the V + ZP group.
      The 16-week results showed growth in all of the test groups, but only one of nine
      teeth showed growth in the zinc oxide-eugenol group and one of 16 teeth in the
      glass-ionomer group. The results of this study indicate that under the conditions
      tested, a glass-ionomer base was capable of minimizing bacterial penetration
      along the material-tooth interface.

PMID- 1991862
TI  - Effect of 2-(methacryloxy)ethyl phenyl hydrogen phosphate on adhesion to dentin.
AB  - A variety of methacrylate-based materials has been developed with the capacity of
      adhering to dentin. This study investigated the effectiveness of 2
      (methacryloxy)ethyl phenyl hydrogenphosphate (phenyl-P) for bonding 5% phenyl-P
      in methyl methacrylate (MMA) to dentinal surfaces. Polymerization of the phenyl
      P/MMA monomer was initiated by partially oxidized tri-n-butyl borane catalyst
      (TBB). The mean tensile bond strength of 5% phenyl-P in MMA to dentin that was
      pre-treated with an aqueous solution of 10% citric acid/3% ferric chloride,
      abbreviated as 10-3, was found to be 10.5 MPa. Scanning electron microscope
      examination demonstrated the formation of a transitional or "hybrid" layer of
      resin-reinforced dentin, created by the intermingling and entanglement of
      polymerized resin with collagen bundles exposed by dentin pre-treatment with 10
      3, an effective remover of the dentinal smear layer. This "hybrid" layer or zone
      was essential for high tensile bond strength to be attained. Phenyl-P was found
      to be effective in promoting monomer diffusion and impregnating monomer into
      demineralized dentinal surfaces. The formation of the "hybrid" layer of resin
      reinforced dentin followed in situ resin polymerization initiated by partially
      oxidized tri-n-butyl borane (TBB). Ferric (Fe3+) ions deposited on dentinal
      surfaces from the 10-3 solution also acted to improve monomer diffusion and
      entanglement with demineralized dentin, and facilitated the formation of the
      "hybrid" layer/zone.

PMID- 1991863
TI  - The effect of catalyst structure on the synthesis of a dental restorative
      monomer.
AB  - The addition product of 2-hydroxyethyl methacrylate (HEMA) and pyromellitic
      dianhydride (PMDA), known as PMDM, is a mixture of two structural isomers. The
      para PMDM isomer--currently used in mediating adhesive bonding of restorative
      materials to hard tooth tissues--is a crystalline solid. The meta isomer is a
      liquid. In the synthesis of PMDM, the para isomer, which can be purified by
      crystallization, is usually present to the extent of only 50% of the product
      mixture. The effect of the amine catalyst structure was studied relative to its
      role in increasing the yield of the para isomer, either by a reduction in the
      amount of the meta isomer or by an increase in the extent of overall reaction.
      The chemical structure of the amine catalyst had an important role in the
      synthesis of PMDM and influenced the ratio of the isomers. Among aliphatic
      amines, especially noteworthy as catalysts that gave excellent yields of the para
      isomer in high purity were N,N-di-isopropyl-ethylamine and
      hexamethylenetetramine.

PMID- 1991864
TI  - Adhesion to dentin and physical properties of a light-cured glass-ionomer
      liner/base.
AB  - The objective of this study was to determine the adhesion to dentin and the
      physical properties of Vitrabond Light Cure Glass Ionomer Liner/Base and to
      compare these values with those of a conventional material, 3M Glass Ionomer
      Liner (3MGI). Shear bond strengths to bovine dentin after 24 h in distilled water
      were determined to be 12 +/- 3 MPa for Vitrabond Liner/Base, while for 3MGI, bond
      strengths were 4 +/- 2 MPa. The failure mode was cohesive in dentin or the
      ionomer. Immediate adhesion of the light-cured material was also significantly
      higher than that of the conventional glass-ionomer liner. Thermal cycling
      experiments showed that the bond of Vitrabond Liner/Base to dentin was a stable
      one. Adhesion studies carried out on human dentin showed high adhesion values as
      well. Compressive and diametral tensile strengths for Vitrabond Liner/Base were
      determined immediately after light curing and also after storage in water for 24
      h, one week, one month, and seven months. There was no significant difference in
      the values of compressive and diametral tensile strengths obtained immediately
      after curing and after extended storage in water at 37 degrees C.

PMID- 1991865
TI  - In vitro fluoride release from a light-cured glass-ionomer liner/base.
AB  - This paper reports the results of an in vitro study of fluoride release from
      Vitrabond Light-Cure Glass Ionomer Liner/Base. The material released fluoride
      ions into the surrounding medium for up to 740 days. The rate of release of
      fluoride ions was independent of the cure time in the range studied. Combining a
      conventional polyalkenoic acid solution with the powder portion of Vitrabond
      Liner/Base did not significantly alter the release profile, thus indicating that
      light curing did not hinder the rate of fluoride release in this system.
      Secondary ion mass spectrometry studies of the dentin underlying the cured glass
      ionomer revealed that there was considerable incorporation of fluoride ions.
      There was no significant change in the mechanical properties of the cured cement
      aged in water at 37 degrees C for prolonged periods, thus indicating that long
      term fluoride release did not adversely affect the strength of this material.

PMID- 1991866
TI  - Dental faculties: dilemmas and challenges.

PMID- 1991867
TI  - Activation of complement by Treponema denticola.
AB  - Oral spirochetes have been shown to be associated with periodontal diseases and
      are present in increased numbers in lesions of greater severity. In this study,
      the interaction of Treponema denticola with human complement, a major
      antibacterial defense system, was examined. For each of two strains of T.
      denticola, it was found that both the classical and alternative pathways of human
      complement were activated in human serum upon incubation at 37 degrees C. C3
      fragments were deposited on the surface of this organism following complement
      activation; the fragments bound included both of the major C3-derived opsonic
      fragments C3b and iC3b. Under incubation conditions identical to those carried
      out for complement activation in serum, T. denticola failed to degrade purified,
      hemolytically-active C3, although it readily degraded inactivated C3. Thus,
      despite the documented proteolytic activity of this organism, complement
      activation and deposition of complement-derived opsonins may be important defense
      mechanisms in the control of infections with T. denticola.

PMID- 1991868
TI  - Power and sample size calculations for clinical trials of myofascial pain of jaw
      muscles.
AB  - When a clinical trial is planned, the approximate number of subjects needed for
      significant differences between/among groups to be detected must be estimated.
      Sample-size calculations provide the investigator with this information. This
      paper discusses the choice of outcome measures and describes the steps used to
      estimate the numbers of subjects necessary for a study that compares treatments
      for patients with chronic myofascial pain of jaw muscles. Within- and between
      subject variances were estimated for the chosen variables, the subjects' pain
      ratings on visual analogue scales. Sample sizes were then calculated for
      theoretical differences between groups by pre-treatment means and overall
      standard deviations (Cohen, 1977). The results of this analysis can be used by
      other researchers when planning studies involving these types of patients.

PMID- 1991869
TI  - Application of the MTT colorimetric assay to measure cytotoxic effects of
      phenolic compounds on established rat dental pulp cells.
AB  - The cytotoxicities of various phenolic compounds were examined using the 3-(4,5
      dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) colorimetric assay
      and established rat dental pulp cells (RPC-C2A). The ID50 (50% inhibition
      concentration) of the phenolic compounds ranged from 0.1 to 10 mmol/L, and the
      cytotoxicities of the phenolic compounds were related to their phenolic
      coefficients. The therapeutic index of each phenolic compound was calculated from
      the ID50 results and from the 50% inhibition concentration for prostaglandin
      synthesis that has been reported previously. Eugenol, guaiacol, and creosol had
      therapeutic indices much higher than those of other phenolic compounds examined.
      This experimental system could be used as a simple preliminary assay to test for
      toxicity of dental drugs and materials.

PMID- 1991870
TI  - Influence of initial flaw size on crack growth in air-tempered porcelain.
AB  - Tempering of dental porcelain by forced convective cooling in air has been shown
      previously to inhibit the sizes of cracks induced in porcelain surfaces. However,
      the depth of compressive stress that is produced by tempering of feldspathic
      porcelain has not been determined. It can be assumed that the potential of
      tempered specimens to inhibit crack formation is reduced as the flaw size exceeds
      some critical value, since the compressive stress decreases with distance from
      the surface. The objective of this study was to test the hypothesis that the
      effectiveness of tempering stress in porcelain decreases with the increasing size
      of initial surface flaws. Body porcelain discs, 16 mm in diameter and 2 mm in
      thickness, were tempered (T) by forced convective cooling in air from an initial
      temperature of 982 degrees C at a pressure of 0.34 MPa for 90 s. Nontempered
      control discs (NT) were slowly cooled by termination of power to the furnace. The
      half crack-lengths (c) of surface cracks induced by a Vickers microhardness
      indenter at loads ranging from 2.0 to 39.2 N were determined initially and over a
      period of 24 h. The initial half crack-lengths, co, for the tempered specimens
      were significantly smaller (p less than 0.05) than the corresponding values for
      the slow-cooled specimens. The mean value of the stress corrosion susceptibility
      coefficient (n), which is inversely related to the slope of log crack size vs.
      log time, was only slightly smaller for the NT specimen groups (15.3), compared
      with the mean value for the T groups (17.1).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1991871
TI  - Effect of cooling rate on leucite volume fraction in dental porcelains.
AB  - Prasad et al. (1988) have shown that slow cooling of dental porcelain produces
      increases in thermal expansion sufficient to make a compatible metal-porcelain
      system incompatible. The present study was undertaken to determine whether the
      increase in porcelain thermal expansion might be attributable to crystallization
      of additional leucite during slow cooling of the porcelain. Eight x-ray
      diffraction specimens for each of six commercial dental porcelains and for the
      Component No. 1 frit of the Weinstein and Weinstein (1962) and Weinstein et al.
      (1962) patents were fabricated and divided into two groups. Specimens in the
      first group (termed fast-cooled) were cooled in the conventional manner by
      removing them from the furnace at the maximum firing temperature immediately into
      room air. Specimens in the second group (termed slow-cooled) were cooled slowly
      by interrupting power to the furnace muffle and allowing them to cool inside the
      closed furnace. Quantitative x-ray diffraction was performed on the fast- and
      slow-cooled porcelain specimens with standards containing leucite volume
      fractions of 0.111, 0.223, 0.334, and 0.445. Unpaired, one-tailed t tests were
      performed on the fast- and slow-cool data, and a significant increase (p less
      than 0.05) in the amount of leucite (as a function of the slow cooling) was found
      for each of the porcelains. The increases in the leucite volume fractions
      resulting from the slow cooling ranged from a low of 8.5% to a high of 55.8%,
      with an average increase of 26.9%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1991872
TI  - Effects of fluoride and chlorhexidine on the microflora of dental root surfaces
      and progression of root-surface caries.
AB  - The effects of fluoride and chlorhexidine varnishes on the microflora of dental
      root surfaces and on the progression of root-surface caries were studied. Forty
      four patients, surgically treated for advanced periodontal disease, were
      distributed at random among three groups. All patients received a standardized
      preventive treatment. Furthermore, the dentition of the patients in the two
      experimental groups was treated, at three-month intervals, with chlorhexidine and
      fluoride varnish, respectively. Patients in the control group received no
      additional treatment. In the experimental groups, plaque samples were collected
      from selected sound and carious root surfaces at baseline and at three, six, and
      nine months after the onset of the study. The presence of root-surface caries was
      scored at baseline and after one year. In addition, the texture, depth, and color
      of the root-surface lesions were monitored. Mutans streptococci on root surfaces
      were suppressed significantly (p less than 0.05) during the whole experimental
      period in the chlorhexidine varnish group, but not in the fluoride varnish group.
      A non-significant increase in the number of Actinomyces viscosus/naeslundii was
      noted after treatment with chlorhexidine and fluoride varnish. The increase in
      the number of decayed and filled root surfaces after one year was significantly
      lower in the experimental groups than in the control group. After treatment with
      chlorhexidine varnish, significantly more initial root-surface lesions had
      hardened than in the other groups.

PMID- 1991873
TI  - Photo-activation of resin cements through porcelain veneers.
AB  - The purpose of this study was to determine the effects of porcelain opacity,
      chemical catalyst, and exposure time on polymerization of light-activated resin
      composite cements. Samples of microfill and hybrid composites, with and without
      catalyst (i.e., dual-cure and visible-light-activated), were polymerized by
      exposure to visible light through porcelain discs of different opacities.
      Microhardness testing (KHN) was used to compare degree of cure for each material
      at various exposure times. Porcelain opacity did not significantly affect
      hardness. However, the results indicated that a chemical catalyst and prolonged
      curing times might be essential for clinical success.

PMID- 1991874
TI  - Therapeutic mineral enrichment of dental plaque visualized by transmission
      electron microscopy.
AB  - The form, location, and distribution of fluorhydroxyapatite deposited in dental
      plaque by a urease-mediated mineral enrichment process have been studied by
      transmission electron microscopy. Artificial plaque was formed in terylene gauze
      in the mouth of one subject and immersed for five min four times per day in a
      mineral-enriching solution. Contralateral control plaque remained untreated. The
      effect on natural plaque was studied in two subjects who withheld oral hygiene
      for four days and mouthrinsed with this solution for two min four times per day
      during the last two days. Mineral deposits were seen in all plaque samples
      exposed to the test solution. None was detected in any control sample. The
      deposits were scattered in the interbacterial matrix as needle-shaped crystals,
      the size and shape of apatite, together with amorphous material. The crystals
      appeared larger and more perfect, and the amorphous material less conspicuous,
      with longer in vivo rinsing periods. Platelet-shaped crystals of octacalcium
      phosphate were never seen. Mineral was also seen within the remnants of dead
      bacterial cells and within degenerating epithelial cells. Crystals were never
      seen within intact bacterial cells, as in calculus formation. The presence of a
      single crystal type and the relative absence of densely-mineralized foci are
      other differences between this mineral-enrichment process and supra-gingival
      calculus formation. A longer-term study is necessary to determine whether the
      solution promotes calculus by providing nucleation seeds.

PMID- 1991875
TI  - Biosynthesis and secretion of rat salivary proteins by Xenopus laevis oocytes.
AB  - Xenopus laevis oocytes injected with poly (A+) RNA isolated from rat parotid and
      submandibular glands synthesize and secrete salivary proteins. Amylase was
      identified in the media of cultured oocytes injected with rat parotid mRNA by
      size and immunoprecipitation with anti-human amylase serum. Secretion of the
      salivary proteins was detectable in the medium eight h following the parotid mRNA
      injection and continued in a time-dependent fashion for up to 96 h. In contrast
      to rat parotid slices in culture, which demonstrate a regulated pathway of
      secretion highly responsive to the secretagogue isoproterenol, secretion of
      salivary proteins by oocytes did not respond to the stimulation by isoproterenol.
      Though parotid mRNA is presumed to contain the templates encoding the regulated
      pathway of secretion, reconstitution of this pathway of secretion in oocytes was
      not observed in our experiments. Since Xenopus laevis oocytes secrete
      constitutively significant amounts of proteins when injected with salivary gland
      mRNA, they are a useful biological system for the analysis of secretion,
      processing, and function of salivary proteins.

PMID- 1991876
TI  - A human periodontal ligament fibroblast clone releases a bone resorption
      inhibition factor in vitro.
AB  - The conditioned media (CM) obtained from three lines of cloned human periodontal
      ligament (PDL) cells were analyzed to determine whether they altered the
      parathyroid hormone (PTH)-stimulated resorption rates (45Ca release) in 48-hour
      cultures of 45Ca-labeled rat long bones. One PDL cell line, PDL-5, produced a
      heat-resistant factor in its CM that inhibited the PTH-stimulated resorption by
      43.8 +/- 9.7 (SE) percent (p less than or equal to 0.02), whereas the CM from the
      other cell lines were without statistically significant effect. The CM from the
      PDL-5 line did not diminish organ culture viability, as determined by 3H
      thymidine incorporation, and did not enhance or diminish the resorption
      inhibiting activity of calcitonin added to the PTH-stimulated cultures. The
      addition of CM from PDL-5 did not alter the bone-resorbing effect of interleukin
      1 (IL-1). These results indicate that CM from PDL-5 inhibits only the PTH-induced
      and not the IL-1-mediated resorption processes, whose mechanisms are therefore
      likely to differ.

PMID- 1991877
TI  - Patterns of epidermal growth factor receptors in basal and squamous cell
      carcinoma.
AB  - The presence of immunoreactive epidermal growth factor receptors in human skin
      tumors was investigated using the indirect immunoperoxidase technique. Sixteen
      basal cell carcinomas and 11 squamous cell carcinomas were evaluated. All of the
      specimens studied were receptor positive. In 70% of the specimens there was
      prominent staining of the cell membranes. In 54% of the nodular basal cell
      carcinoma specimens there was increased staining at the periphery of the tumor
      cell masses.

PMID- 1991878
TI  - Basal cell carcinoma recurring after radiotherapy: a unique, difficult treatment
      subclass of recurrent basal cell carcinoma.
AB  - Twenty-seven basal cell carcinomas (BCCs) recurring following radiation therapy
      alone or in addition to other treatment modalities were treated with Mohs
      micrographic surgery (MMS) from 1983 to 1989. Mean tumor size was 2.1 cm. Of the
      tumors, 70.4% arose in the mid-face region, 55.6% had undergone multiple previous
      treatment modalities. The present recurrence rate is 7.4% (mean follow-up: 25
      months). Basal cell carcinoma recurring following radiotherapy deserves special
      subclassification among recurrent BCC. It is very difficult to eradicate, with
      high recurrence rates following standard surgical excision or further
      radiotherapy. Tumors are usually large, aggressive, and invasive. Most arise in
      the cosmetically crucial mid-face region, where extension into subcutaneous
      tissue planes is common. Mohs surgery, with its inherent abilities to examine all
      margins, map tumor extension, and conserve tissue, is uniquely suited to
      treatment of these difficult tumors.

PMID- 1991879
TI  - Skin ultrasound in dermatologic surgical planning.
AB  - High-resolution ultrasonography was performed on 55 patients with palpable skin
      lesions, all submitted to surgical excision and to histologic diagnosis. In all
      the cases, the ultrasound picture was confirmed by the surgical appearance of the
      lesions. The sonographic structure was characteristic in the case of cysts and
      angiomas, lymphangiomas in particular. Ultrasonography is considered a simple and
      reliable technique for the pre-operative evaluation of skin nodules, as it gives
      a clear picture of their size, depth, and outline. However, sonography cannot
      substitute for the clinical dermatologic approach and the need for an histologic
      diagnosis.

PMID- 1991880
TI  - Prospective follow-up for malignant melanoma in patients with atypical-mole
      (dysplastic-nevus) syndrome.
AB  - A total of 357 white patients who had melanocytic nevi that fulfilled the
      clinical criteria for the "classic" atypical-mole (dysplastic-nevus) syndrome
      (100 or more melanocytic nevi; one or more melanocytic nevi 8 mm or larger in
      diameter; and, one or more melanocytic nevi with atypical features) were followed
      for the development of cutaneous malignant melanomas. Seventeen patients (4.8%)
      developed malignant melanomas during an average follow-up period of 49 months.
      One patient developed two malignant melanomas. Eight of the malignant melanomas
      detected were in situ and ten were invasive melanomas (less than 0.86 mm in
      Breslow thickness), implying an excellent prognosis. The number of malignant
      melanomas detected in these patients exceeded significantly the number expected
      to occur in age- and sex-matched white controls. All groups were shown to have an
      increased risk for the development of malignant melanomas. Total-body photographs
      were helpful in detecting changes in size, shape, and color that led to the
      diagnosis of malignant melanoma. These data support the concept that patients
      with this readily regionalized clinical presentation of classic atypical-mole
      syndrome are at an increased risk for malignant melanomas and, therefore, should
      be examined regularly.

PMID- 1991881
TI  - Incisional slit grafting.
AB  - Incisional slit grafting, a new and greatly improved technique in hair
      transplantation, is described. Incisional slit grafting utilizes larger numbers
      of smaller grafts than does traditional punch grafting. No tissue is removed from
      the recipient bed. The vascular supply is conserved, resulting in an increased
      graft yield. The clumping and stalking effect associated with traditional round
      grafting is eliminated largely, and a more natural frontal hairline is achieved.

PMID- 1991882
TI  - How many treatments are necessary to sclerose varicose and telangiectatic leg
      veins?

PMID- 1991884
TI  - The medical necessity of evaluation and treatment of port-wine stains.
AB  - New lasers and improved laser delivery systems have allowed for the safe and
      effective treatment of port-wine stains in patients of all ages. The satisfactory
      results obtained by laser treatment have increased the number of patients seeking
      consultation regarding their birthmarks. It is imperative that physicians
      recognize the various medical syndromes and problems associated with port-wine
      stains. A review of 415 patients with facial port-wine stains has revealed
      hypertrophy and/or nodularity in 65% of patients by the fifth decade of life,
      which increases significantly the morbidity of these lesions. It is believed that
      laser treatment will minimize the medical and psychologic complications that
      result from the natural evolution of port-wine stains.

PMID- 1991883
TI  - Sclerotherapy of varicose and telangiectatic leg veins. Minimal sclerosant
      concentration of hypertonic saline and its relationship to vessel diameter.
AB  - The author reports the results of a double-blind, paired-comparison study using
      saline sclerosant plus or minus heparin additive. The study was designed to
      elucidate the effects of increasing concentrations of hypertonic saline with
      regard to vessel diameter, clinical efficacy, complications, and discomfort. Six
      hundred women with bilaterally symmetrical starburst telangiectasias or varicose
      veins were entered into the study. Sodium chloride 11.7% appeared to be the
      minimal sclerosant concentration of saline that produced the most effective vein
      sclerosis of vessels of less than 8 mm in diameter, while producing the least
      morbidity. The optimal concentration of the sclerosant may vary with the diameter
      of the vessels under therapeutic consideration.

PMID- 1991885
TI  - Hair transplantation (a new method for recipient site suturing): the upper dermal
      running stitch.
AB  - Recipient hair transplant plugs may heal into place with palpable, and
      unfortunately, visible borders. This appearance, called "cobblestoning," is
      reminiscent of the bumps in a cobblestone street. The author presents a new,
      rapid method of suturing transplanted plugs that greatly reduces cobblestoning,
      virtually eliminates traumatic plug loss, and facilitates row-by-row hair
      transplantation. Additionally, postoperative bandaging is not necessary, shower
      cleansing may commence within hours, and postoperative activity may be unlimited.

PMID- 1991886
TI  - Natural history of moderate aortic stenosis.
AB  - The natural history of severe, symptomatic aortic stenosis has been well
      documented. However, the natural history of moderate aortic stenosis remains
      poorly understood. Therefore, a group of 66 patients was identified who had a
      diagnosis of moderate aortic stenosis at the time of cardiac catheterization
      (aortic valve area 0.7 to 1.2 cm2) and who did not have surgical therapy during
      the 1st 180 days after cardiac catheterization. During a mean follow-up period of
      35 months, 14 patients died of causes attributed to aortic stenosis and 21
      underwent aortic valve replacement. The estimated probability for remaining free
      of any complication of aortic stenosis at the end of the first 4 years was 59%.
      Symptomatic patients with decreased ejection fraction or hemodynamic evidence of
      left ventricular decompensation were at greater risk for these complications. It
      is concluded that patients with moderate aortic stenosis are at significant risk
      for the development of complications.

PMID- 1991887
TI  - Clinical and electrophysiologic determinants, treatment and survival of patients
      with sustained malignant ventricular tachyarrhythmias occurring late after
      myocardial infarction.
AB  - To assess the clinical and electrophysiologic determinants, treatment and
      survival of patients with sustained malignant ventricular tachyarrhythmias late
      after myocardial infarction, a total of 108 patients (mean age 61 +/- 10 years)
      were studied. Thirty-two patients (Group I) had sustained ventricular
      tachyarrhythmias 8 to 60 days (mean 13 +/- 9) after acute myocardial infarction.
      The remaining 76 patients (Group II), who served as a control group, had no
      sustained ventricular tachyarrhythmias less than or equal to 60 days after
      infarction. The most significant independent determinants of sustained
      ventricular tachyarrhythmias late after infarction were the presence of late
      potentials (chi square = 16.07, p = 0.0001), defined as an abnormal signal
      averaged QRS complex in association with an abnormal root-mean-square voltage in
      the terminal 40 ms of the QRS complex, and an abnormal ejection fraction of less
      than 40% (chi square = 10.09, p = 0.001). Sustained ventricular tachycardia was
      induced in 27 (96%) of 28 Group I patients. Among the 32 patients in Group I,
      antitachycardia therapy included antiarrhythmic drug therapy as the sole
      preventive measure in 14 (44%); map-guided surgery or coronary artery bypass
      surgery, or both, in 14 (44%) and the automatic cardioverter-defibrillator in 4
      (12%). The arrhythmias were rendered noninducible in 83% of patients after map
      guided surgery and in 41% after drug therapy. During a follow-up period of 20 +/-
      14 months, five Group I patients (15%) had an arrhythmic event and four (9.3%)
      had a cardiac-related death. All five patients who had an arrhythmic event were
      receiving antiarrhythmic drug therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1991888
TI  - Sustained ventricular tachyarrhythmias after infarction: when should the worrying
      begin?

PMID- 1991889
TI  - Effect of H1 receptor stimulation on coronary artery diameter in patients with
      variant angina: comparison with effect of acetylcholine.
AB  - It has been suggested that histamine is involved in the pathogenesis of coronary
      spasm but its exact role remains unclear. H1 receptor stimulation of the coronary
      artery was performed with a selective intracoronary infusion of histamine (2
      micrograms/min) in 21 patients with variant angina after blockade of the H2
      receptor with cimetidine (25 mg/kg) and its effect on the coronary artery
      diameter was examined. Intracoronary injection of acetylcholine was also
      performed in 19 of the 21 patients. Ergonovine (0.2 mg) was intravenously
      administered in one patient. The coronary artery diameter was measured with
      cinevideodensitometric analysis. A mean plasma histamine concentration in the
      coronary sinus increased from 4 x 10(-9) to 7 x 10(-8) M 5 min after histamine
      infusion into the left coronary artery (n = 18). Coronary spasm was induced in 6
      patients (29%) with histamine, in 18 (95%) with acetylcholine and in 1 with
      ergonovine. The effect of histamine on the luminal diameter was analyzed at the
      site of spasm in the 26 coronary arteries in which spasm was induced by
      acetylcholine or ergonovine. Of the 20 coronary arteries with a normal
      arteriogram or a fixed stenosis less than or equal to 50% of luminal diameter,
      histamine decreased the diameter in 4, increased it in 14 (70%) and caused no
      change in 2; of the 6 coronary arteries with a fixed stenosis greater than or
      equal to 75%, histamine decreased the diameter in 5 and increased it in 1. In the
      coronary arteries in which spasm was not induced by either acetylcholine or
      ergonovine, histamine increased the diameter, especially in those without
      advanced atherosclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1991890
TI  - Percutaneous mitral valvuloplasty in surgical high risk patients.
AB  - Among 126 consecutive patients undergoing percutaneous mitral valvuloplasty, 34
      were judged to be at high risk for surgery on the basis of age greater than 70
      years (n = 13), New York Heart Association functional class IV (n = 11), ejection
      fraction less than or equal to 35% (n = 3), severe pulmonary hypertension (n =
      7), need for associated coronary bypass (n = 4) or additional valve surgery (n =
      20) or severe pulmonary disease (n = 3). Baseline features of the high risk group
      were substantially worse than those of the other patients: age (65 +/- 11 versus
      49 +/- 12 years; p = 0.0001) and echocardiographic score (9.4 +/- 1.8 versus 8.2
      +/- 1.5; p = 0.005) were higher, whereas cardiac output (2.9 +/- 0.9 versus 4.1
      +/- 1.2 liters/min; p = 0.0001) and mitral valve area (0.9 +/- 0.4 versus 1.1 +/-
      0.3 mm2; p = 0.002) were lower. Three high risk patients experienced technical
      failures and three others had major complications. Among the remaining 28
      patients, 18 (65%) had a complete hemodynamic success, 4 (14%) an incomplete
      success and 6 (21%) hemodynamic failure. Stepwise logistic regression analysis
      retained echocardiographic score as the only factor independently predictive of
      success. The percent increase in mitral valve area also correlated with
      echocardiographic score (r = 0.51, p less than 0.01).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1991891
TI  - The variable extent of jeopardized myocardium in patients with single vessel
      coronary artery disease: quantification by thallium-201 single photon emission
      computed tomography.
AB  - To assess the extent of jeopardized myocardium in patients with single vessel
      coronary artery disease of variable severity and location, quantitative exercise
      thallium-201 single photon emission computed tomography was performed in 158
      consecutive patients with angiographically proved single vessel coronary artery
      disease. The extent of abnormal left ventricular perfusion was quantified from
      computer-generated polar maps of three-dimensional myocardial radioactivity.
      Patients with only a moderate (51% to 69%) stenosis tended to have a small
      perfusion defect irrespective of the coronary artery involved. Whereas a
      perfusion defect measuring greater than or equal to 10% of the left ventricle was
      found in 78% of patients with no prior infarction and severe (greater than or
      equal to 70%) stenosis, this was observed in only 24% of patients with moderate
      stenosis. Perfusion defect size increased with increasing severity of stenosis
      for the entire group without infarction and for those with left anterior
      descending, right and circumflex coronary artery stenosis. However, the
      correlation between stenosis severity and perfusion defect size was at best only
      modest (r = 0.38, p = 0.0001). The left anterior descending artery was shown to
      be the most important of the three coronary arteries for providing left
      ventricular perfusion. Proximal stenosis of this artery produced a perfusion
      defect approximately twice as large as that found in patients with a proximal
      right or circumflex artery stenosis. However, marked heterogeneity in perfusion
      defect size existed among all three vessels despite comparable stenosis severity.
      This was most apparent for the left anterior descending coronary artery, where
      mid vessel stenosis commonly produced a perfusion defect similar in size to that
      found in proximally stenosed vessels.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1991892
TI  - Relation between functional and anatomic descriptors of coronary artery disease.

PMID- 1991893
TI  - Differentiating cardiomyopathy of coronary artery disease from nonischemic
      dilated cardiomyopathy utilizing positron emission tomography.
AB  - To determine if imaging of blood flow (using N-13 ammonia) and glucose metabolism
      (using F-18 2-deoxyglucose) with positron emission tomography can distinguish
      cardiomyopathy of coronary artery disease from nonischemic dilated
      cardiomyopathy, 21 patients with severe left ventricular dysfunction who were
      evaluated for cardiac transplantation were studied. The origin of left
      ventricular dysfunction had been previously determined by coronary angiography to
      be ischemic (11 patients) or nonischemic (10 patients). Images were visually
      analyzed by three observers on a graded scale in seven left ventricular segments
      and revealed fewer defects in dilated cardiomyopathy compared with ischemic
      cardiomyopathy for N-13 ammonia (2.7 +/- 1.6 versus 5 +/- 0.6; p less than 0.03)
      and F-18 deoxyglucose (2.8 +/- 2.1 versus 4.6 +/- 1.1; p less than 0.03). An
      index incorporating extent and severity of defects revealed more homogeneity with
      fewer and less severe defects in subjects with nonischemic than in those with
      ischemic cardiomyopathy as assessed by imaging of flow (2.8 +/- 1.8 versus 9.2 +/
      3; p less than 0.001) and metabolism (3.8 +/- 3.3 versus 8.5 +/- 3.6; p less
      than 0.005). Diagnostic accuracy for distinguishing the two subgroups by visual
      image analysis was 85%. Using previously published circumferential count profile
      criteria, patients with dilated cardiomyopathy had fewer ischemic segments (0.4
      +/- 0.8 versus 2.5 +/- 2 per patient; p less than 0.01) and infarcted segments
      (0.1 +/- 0.3 versus 2.4 +/- 1.4 per patient; p less than 0.001) than did patients
      with cardiomyopathy of coronary artery disease. The sensitivity for
      differentiating the two clinical subgroups using circumferential profile analysis
      was 100% and the specificity 80%. An index incorporating both number and severity
      of defects derived from circumferential profile analysis was significantly lower
      in subjects with dilated cardiomyopathy than in ischemic cardiomyopathy (0.3 +/-
      0.8 versus 2.7 +/- 2.4; p less than 0.005). Thus, noninvasive positron emission
      tomographic imaging with N-13 ammonia and F-18 deoxyglucose is helpful in
      distinguishing patients with severe left ventricular dysfunction secondary to
      coronary artery disease from those with nonischemic cardiomyopathy, and a
      semiquantitative index such as circumferential profile analysis is superior to
      that of visual analysis alone.

PMID- 1991895
TI  - Drug therapy for ventricular tachyarrhythmias: how many electropharmacologic
      trials are appropriate?
AB  - To determine how many electropharmacologic drug trials should be performed to
      select therapy for patients with ventricular tachyarrhythmias, the outcome of 150
      consecutive patients with inducible ventricular tachyarrhythmias undergoing
      serial electropharmacologic testing was examined. The probability of identifying
      predicted effective therapy (inductive of fewer than five ventricular responses
      with three ventricular extrastimuli at three pacing cycle lengths) and the
      probability of that therapy preventing sustained ventricular tachyarrhythmia
      recurrences were determined as a function of the number of preceding trials. The
      probability ( +/- SE) of identifying predicted effective therapy by the first
      trial (0.23 +/- 0.03) was significantly higher than that of the second (0.09 +/-
      0.04), third (0.08 +/- 0.04) and fourth (0.05 +/- 0.04) trials (p = 0.001). No
      patient had predicted effective therapy identified by subsequent trials. The 2
      year actuarial probability of freedom from sustained ventricular tachyarrhythmias
      on predicted effective therapy was higher for the first (0.79 +/- 0.08), second
      (0.73 +/- 0.13) and third (0.86 +/- 0.13) trials than for the fourth (0.33 +/-
      0.27) trial (p = 0.02). Thus, the probability of selecting therapy with long-term
      efficacy was highest for the first trial (0.18), intermediate for the second
      (0.07) and third (0.07) trials and lowest for the fourth (0.02) and subsequent
      (0.00) trials. Accordingly, the electropharmacologic approach to therapy
      selection should be abandoned after three unsuccessful trials.

PMID- 1991894
TI  - A randomized comparison of the nephrotoxicity of iopamidol and diatrizoate in
      high risk patients undergoing cardiac angiography.
AB  - Three hundred seven high risk patients with renal impairment (serum creatinine
      greater than or equal to 1.5 mg/dl) were randomized in a double-blind manner to
      either iopamidol (a nonionic, low osmolar radiocontrast agent) or diatrizoate (a
      conventional radiocontrast agent) at cardiac angiography with subsequent follow
      up study of renal function. Baseline clinical and angiographic variables were
      similar in the iopamidol (n = 155) and diatrizoate (n = 152) groups. Change in
      renal function after angiography was less pronounced with iopamidol compared with
      diatrizoate as measured by mean ( +/- SD) increase in 24 h serum creatinine (0.11
      +/- 0.2 versus 0.22 +/- 0.26 mg/dl, p less than 0.001), mean maximal increase in
      serum creatinine (0.2 +/- 0.44 versus 0.38 +/- 0.73 mg/dl, p less than 0.0001)
      and percent of patients with a maximal increase in serum creatinine greater than
      0.5 mg/dl (8% versus 19%, p less than 0.01). Such differences could not be
      documented in diabetic patients using insulin. There was no significant
      difference between agents in the number of patients developing clinically severe
      acute renal dysfunction. It is concluded that iopamidol is less nephrotoxic than
      diatrizoate in high risk patients at cardiac angiography. However, the difference
      in nephrotoxicity is small, of no major clinical significance in the majority of
      high risk patients and could not be documented in insulin-using diabetic
      patients. Iopamidol may be the preferred agent in certain patients with advanced
      renal impairment, but further study is warranted.

PMID- 1991896
TI  - Comparison of pre- and postoperative conduction patterns in patients surgically
      cured of atrioventricular node reentrant tachycardia.
AB  - Patients with atrioventricular (AV) node reentrant tachycardia characteristically
      have short and constant retrograde His-atrium conduction times (H2A2 intervals)
      during the introduction of ventricular extrastimuli. It has therefore been
      suggested that the tachycardia circuit involves retrograde conduction up an
      accessory pathway located in perinodal tissue. If the mechanism of surgical cure
      of AV node reentrant tachycardia is interruption of this accessory pathway,
      postoperative changes in retrograde conduction would be expected. Thirteen
      patients with drug-refractory AV node reentrant tachycardia underwent surgery.
      Preoperatively, H2A2 intervals were short and constant. During AV node reentrant
      tachycardia, earliest atrial activation was seen near the His bundle and was 0 to
      25 ms before ventricular activation in all patients except one. Surgery consisted
      of dissection of right atrial septal and anterior inputs to the AV node and
      central fibrous body. Postoperatively, the H2A2 interval remained short and
      constant compared with preoperative values although it was slightly prolonged (74
      +/- 18 versus 61 +/- 21 ms, p less than 0.005). Twelve of the 13 patients are
      free of tachycardia after 28 +/- 13 months and no patient has had evidence of AV
      node block. Thus, surgical cure of AV node reentrant tachycardia is highly
      successful; however, there is no reason to postulate an accessory pathway or use
      of perinodal tissue as part of the tachycardia circuit and the mechanism of
      surgical success remains obscure.

PMID- 1991897
TI  - Prolonged and fractionated right atrial electrograms during sinus rhythm in
      patients with paroxysmal atrial fibrillation and sick sinus node syndrome.
AB  - Intraatrial catheter mapping of the right atrium was performed during sinus
      rhythm in 92 patients: Group I = 43 control patients without paroxysmal atrial
      fibrillation or sick sinus node syndrome; Group II = 31 patients with paroxysmal
      atrial fibrillation but without sick sinus node syndrome; and Group III = 18
      patients with both paroxysmal atrial fibrillation and sick sinus node syndrome.
      Atrial electrograms were recorded at 12 sites in the right atrium. The duration
      and number of fragmented deflections of the atrial electrograms were
      quantitatively measured. The mean duration and number of fragmented deflections
      of the 516 atrial electrograms in Group I were 74 +/- 11 ms and 3.9 +/- 1.3,
      respectively. The criteria for an abnormal atrial electrogram were defined as a
      duration of greater than or equal to 100 ms or eight or more fragmented
      deflections, or both. Abnormal atrial electrograms were observed in 10 patients
      (23.3%) in Group I, 21 patients (67.7%) in Group II and 15 patients (83.3%) in
      Group III (Group II versus Group I, p less than 0.001; Group III versus Group I,
      p less than 0.001). The mean number of abnormal electrograms per patient with an
      abnormal electrogram was 1.3 +/- 0.7 in Group I, 2.5 +/- 1.9 in Group II and 3.5
      +/- 2.5 in Group III (Group I versus Group II, p less than 0.01; Group II versus
      Group III, p less than 0.05). A prolonged and fractionated atrial electrogram
      characteristic of paroxysmal atrial fibrillation can be closely related to the
      vulnerability of the atrial muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1991898
TI  - Spontaneous changes in ventricular tachycardia cycle length.
AB  - Understanding spontaneous fluctuations in ventricular tachycardia cycle length is
      required to develop algorithms for ventricular tachycardia detection and
      termination. Variations in cycle length, time to stable cycle length and the
      range of RR intervals during ventricular tachycardia were analyzed in 74 episodes
      of sustained monomorphic ventricular tachycardia induced in patients not taking
      antiarrhythmic medication. Linear regression demonstrated cycle length
      variability to decrease over time (41 +/- 24 to 17 +/- 19 ms, p less than 0.001).
      Slower ventricular tachycardia had more cycle length variability than faster
      ventricular tachycardia (p less than 0.001). Ventricular tachycardia that was
      initially more variable tended to remain more variable (p less than 0.001). Fifty
      four percent of episodes stabilized within the first 15 beats, 75% by 30 beats
      and 93% by 50 beats. The number of beats to stable cycle length was independent
      of ventricular tachycardia rate. The average range in cycle length per episode
      was 127 +/- 72 ms; 12% of ventricular tachycardia episodes varied by less than 50
      ms and 45% by less than 150 ms. The maximal range in RR intervals from a single
      episode of ventricular tachycardia was 290 ms. Therefore, ventricular tachycardia
      demonstrates a wide range of cycle lengths and has time-dependent changes in
      variability and stability. These cycle length changes should be considered in the
      algorithms for ventricular tachycardia detection and termination by automatic
      antitachycardia devices.

PMID- 1991900
TI  - Restenosis after percutaneous transluminal coronary angioplasty: pathologic
      observations in 20 patients.
AB  - Histopathologic examination was performed in 20 patients undergoing antemortem
      coronary angioplasty. Thirty-four lesions were dilated and the interval between
      coronary angioplasty and death ranged from several hours to 4 years. Intimal
      proliferation of smooth muscle cells, as a major cause of restenosis, was
      observed in 83% to 100% of 28 lesions examined 11 days to 2 years after coronary
      angioplasty. In 20 lesions examined within 6 months, proliferating smooth muscle
      cells were predominantly of the synthetic type and there was abundant
      extracellular matrix substance chiefly composed of proteoglycans. In eight
      lesions examined between 6 months and 2 years, contractile type smooth muscle
      cells were dominant and extracellular matrix was composed chiefly of collagen. In
      three lesions examined after 2 years, evidence of antemortem coronary angioplasty
      was hardly identifiable and these lesions were almost indistinguishable from
      conventional atherosclerotic plaque. These temporal changes in histologic pattern
      provide a pathologic background for clinical reports that restenosis is
      predominantly found within 6 months after coronary angioplasty. Morphometric
      analysis revealed that the extent of intimal proliferation was significantly
      greater in lesions with evidence of medial or adventitial tears than in lesions
      with no or only intimal tears.

PMID- 1991899
TI  - Automatic implantable cardioverter-defibrillator implantation without thoracotomy
      using an endocardial and submuscular patch system.
AB  - The automatic cardioverter-defibrillator lead system is implanted by a
      thoracotomy procedure that may result in atelectasis, pleural effusion, cardiac
      tamponade and lengthy convalescence. A new defibrillator lead system that allows
      selection of different defibrillating current pathways is implanted without a
      thoracotomy. Ten patients requiring a cardioverter-defibrillator for recurrent
      sustained ventricular tachycardia (five patients) or aborted sudden cardiac death
      (five patients) were evaluated for implantation of this lead system. A lead
      configuration with a bidirectional defibrillating current pathway was implanted
      in nine patients. The defibrillation threshold with this lead configuration was
      15 J in five patients, 20 J in three and 30 to 35 J in one patient. In the
      remaining patient the lead system had a 40 J defibrillation threshold and was not
      implanted. No perioperative complications occurred. Induced ventricular
      fibrillation was successfully terminated at the predischarge and intermediate
      follow-up (8 to 12 weeks) electrophysiologic studies. During the follow-up
      period, there were three deaths (one sudden, two due to heart failure) and two
      lead system failures (oversensing with inappropriate shocks in one patient and
      patch lead fracture in another). Implantation of the cardioverter-defibrillator
      lead system by a nonthoracotomy approach is feasible, has no significant
      perioperative complications and is well tolerated by patients. Effective
      defibrillation was demonstrated immediately as well as at intermediate follow-up
      study. The occurrence of patch lead fracture and oversensing requires improvement
      in the present (nonthoracotomy) lead system technology.

PMID- 1991901
TI  - What does pathology teach us about recurrent stenosis after coronary angioplasty?

PMID- 1991902
TI  - Differential histopathology of primary atherosclerotic and restenotic lesions in
      coronary arteries and saphenous vein bypass grafts: analysis of tissue obtained
      from 73 patients by directional atherectomy.
AB  - Vascular tissue obtained using a directional percutaneous atherectomy device was
      examined microscopically. Tissue was obtained from coronary arteries without
      prior instrumentation (primary lesions, n = 31), aortocoronary saphenous vein
      bypass grafts with primary lesions (n = 8), coronary arteries with lesions
      developing after prior balloon angioplasty or mechanical atherectomy (restenotic
      lesions, n = 30) and vein bypass grafts with restenotic lesions (n = 4). Primary
      lesions were characterized by dense intimal fibrosis with necrotic debris (83% of
      intimal tissue) and foam cells typical of atherosclerosis. These lesions
      frequently contained cholesterol crystals (45% of coronary arteries, 50% of vein
      grafts) and calcium deposits (65% of coronary arteries, 38% of vein grafts).
      Restenotic lesions were characterized by an increased proportion of loose
      fibroproliferative tissue (45% of coronary artery intima, 35% of vein graft
      intima). Immunohistochemical stains confirmed this proliferative tissue to be
      primarily smooth muscle cells. Thrombus was rarely observed. Comparison of
      resected tissues indicated that dense fibrosis and necrosis are significantly
      more common in primary than in restenotic lesions (83% versus 56% of intimal
      tissue, p = 0.0005), whereas smooth muscle cell hyperplasia is more common in
      restenotic than in primary lesions (44% versus 17% of intimal tissue, p less than
      0.0005). Partial-thickness resection of medial tissue or full-thickness resection
      of media with associated adventitial tissue occurred in 27 (56%) of 39 primary
      atheromatous lesions and 16 (47%) of 34 restenotic lesions; subintimal tissue
      obtained from primary lesions appeared identical to that obtained from restenotic
      lesions. These data indicate that the histopathologic characteristics of the
      neointimal layer of restenotic lesions differ from those of the intimal layer of
      primary atherosclerotic lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1991903
TI  - Transplant coronary artery disease: histopathologic correlations with
      angiographic morphology.
AB  - Accelerated coronary artery disease is a major cause of morbidity and mortality
      among cardiac transplant recipients. Ten patients who died or underwent
      retransplantation within 2 months of coronary angiography had direct correlation
      of angiographic (normal discrete lesions, diffuse concentric narrowing) with
      histologic appearance of coronary arteries. Of the 26 angiographically normal
      segments, 73% showed mild to moderate fibrous intimal thickening by light
      microscopy. The remainder had intermediate lesions or atheromatous plaques.
      Discrete stenoses usually corresponded to lipid-rich intermediate or atheromatous
      disease. In contrast, angiographically diffuse, concentrically narrowed lesions
      usually were areas of severe fibrous intimal thickening. Fresh or organizing
      thrombus was most often associated with discrete lesions and accounted for all
      complete occlusions. Histologic and angiographic comparisons of the degree of
      luminal narrowing showed generally good correlation for high grade stenoses.
      Lesions graded as having less than 25% diameter narrowing were often
      underestimated angiographically as compared with histologic determinations.
      Transplant coronary artery disease has a heterogeneous histologic and
      angiographic appearance, with angiographic underestimation of disease in some
      patients.

PMID- 1991904
TI  - Immunosuppressive therapy in the management of acute myocarditis in children: a
      clinical trial.
AB  - To assess whether steroid therapy influenced the clinical course of myocarditis
      in a pediatric population, findings in 13 consecutive infants and children (8
      female, 5 male) with biopsy-proved myocarditis were reviewed. The mean age was
      5.7 +/- 4.8 years (range 1.1 to 14.8). Congestive heart failure was present in
      all as were ST-T wave changes, cardiomegaly and pulmonary edema on chest
      roentgenogram. Echocardiography demonstrated pericardial effusion in five
      patients and mitral regurgitation in eight. Mean left ventricular ejection
      fraction was 34 +/- 12%. Prednisone was administered to all patients; one patient
      also received azathioprine. There was one death. All survivors showed clinical
      improvement with normalization of ECG changes, heart size and systolic function.
      No significant side effects occurred. Repeat myocardial biopsy in eight patients
      demonstrated improvement in all eight and elimination of the inflammatory
      infiltrate in six. Immunosuppressive therapy in this pediatric population
      appeared useful in improving the clinical course and cardiac function in acute
      myocarditis with no adverse side effects.

PMID- 1991905
TI  - Lung function and pulmonary regurgitation limit exercise capacity in
      postoperative tetralogy of Fallot.
AB  - Fifty-five patients with repair of tetralogy of Fallot were evaluated with
      treadmill exercise, pulmonary function testing and rest two-dimensional and
      Doppler echocardiography to determine the relation among cardiopulmonary
      function, exercise capacity and ventricular arrhythmias. The mean age at repair
      was 8.1 +/- 2.1 years; age at the time of study ranged from 15 to 37 years (mean
      follow-up time after repair 18 +/- 5 years). Exercise duration was 92 +/- 17% of
      predicted. Maximal heart rate was 94 +/- 7% of predicted. No exercise test was
      stopped because of an arrhythmia. Thirty patients had oxygen consumption and
      ventilation measured during their final minute of exercise. Peak oxygen
      consumption was 31 +/- 8 ml/kg per min (86 +/- 18% of predicted). Twenty-five
      patients (45%) had low vital capacity at rest (less than 80% of predicted).
      Pulmonary regurgitation was identified in 42 (75%) of the patients and judged to
      be moderate in 10 (18%). Mild tricuspid valve regurgitation was identified in
      64%. Doppler estimated right ventricular outflow gradient was greater than 15 mm
      Hg in 15% of the patients (mean gradient 24 mm Hg [range 16 to 56]). Age at
      repair, duration of follow-up and type of repair did not correlate with
      echocardiographic variables, ventilatory data, exercise performance or
      arrhythmias. Moderate pulmonary regurgitation was associated with increased right
      ventricular diastolic area and both were inversely related to exercise duration
      and vital capacity. Decreased breathing reserve during maximal exercise was
      associated with moderate pulmonary regurgitation and decreased vital capacity.
      The results indicate that exercise capacity in these patients is in general good;
      however, right ventricular volume loading and ventilatory dysfunction may produce
      exercise limitation.

PMID- 1991907
TI  - The Mansfield Scientific Aortic Valvuloplasty Registry: overview of acute
      hemodynamic results and procedural complications.
AB  - Between December 1, 1986 and October 30, 1987, balloon aortic valvuloplasty was
      performed in 492 patients with aortic stenosis (mean age 79 +/- 8.4 years)
      enrolled in the Mansfield Scientific Aortic Valvuloplasty Registry. All
      procedures were performed from a femoral approach (92%), brachial approach (6%)
      or transseptal approach (2%) and utilized either a single balloon technique (72%)
      or a double balloon technique (28%). Valvuloplasty resulted in a significant
      improvement in aortic valve area (0.50 +/- 0.18 cm2 to 0.82 +/- 0.30 cm2), mean
      aortic valve gradient (60 +/- 23 mm Hg to 30 +/- 13 mm Hg) and cardiac output
      (3.86 +/- 1.26 to 4.05 +/- 1.31 liters/min). Serial aortography demonstrated a
      moderate or severe increase in aortic insufficiency in only 2.1% of patients.
      Statistical analysis of the procedural factors affecting acute valvuloplasty
      results demonstrated significant correlations of single versus double balloon
      technique, total number of balloon inflations and total number of balloon
      exchanges with respect to the absolute change in mean aortic valve gradient
      occurring during the valvuloplasty procedure. In addition, there was a
      significant correlation between the maximal time of valvuloplasty balloon
      inflation with aortic valve area measured after valvuloplasty, and there were
      significant correlations of the total number of balloon inflations and total
      number of balloon exchanges with the aortic valve mean gradient measured after
      valvuloplasty. The overall complication rate for the procedure was 20.5%,
      including vascular injury in 11%, embolic phenomenon in 2.2%, ventricular
      perforation resulting in tamponade in 1.8%, massive aortic insufficiency in 1%,
      nonfatal arrhythmia in 0.8% and myocardial infarction in 0.2%.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1991906
TI  - Effect of atenolol and diltiazem on heart period variability in normal persons.
AB  - Several time and frequency domain measures of heart period variability are
      reduced 1 to 2 weeks after myocardial infarction, and a reduced standard
      deviation of normal RR intervals over a 24 h period (SDNN) is associated with
      increased mortality. The predictive accuracy of heart period variability may be
      reduced by drugs used to treat patients after myocardial infarction. Accordingly,
      a randomized, three period, placebo-controlled, crossover (Latin square) design
      was used to determine the effect of atenolol and diltiazem on time and frequency
      measures of heart period variability calculated from 24 h continuous
      electrocardiographic recordings during treatment with atenolol, diltiazem and
      placebo in 18 normal volunteers. During atenolol treatment, the 24 h average
      normal RR (NN) interval increased 24% (p less than 0.001). The three measures of
      tonic vagal activity were significantly increased (p less than 0.001) during
      atenolol treatment: percent of successive normal RR intervals greater than 50 ms
      = 69%, root mean square successive difference of normal RR intervals = 61% and
      high frequency power in the heart period power spectrum = 84%. Low frequency
      power also increased 45% (p less than 0.01), indicating that this variable also
      is an indicator of tonic vagal activity over 24 h. Diltiazem had no significant
      effect on the 24 h average NN interval or on any measure of heart period
      variability. The decreased mortality rate after myocardial infarction associated
      with beta-adrenergic blocker but not calcium channel blocker therapy may be
      attributed in part to an increase in vagal tone caused by beta-blockers.

PMID- 1991908
TI  - Association between primary pulmonary hypertension and portal hypertension:
      analysis of its pathophysiology and clinical, laboratory and hemodynamic
      manifestations.
AB  - To determine the clinical, laboratory and hemodynamic profile in patients with
      primary pulmonary hypertension and associated portal hypertension, 7 new cases
      and 71 previously reported cases were analyzed. There was no gender predilection
      and the average age at diagnosis was 41 years. Liver cirrhosis was the most
      frequent cause of hypertension (82%) and a surgical portosystemic shunt was
      present in 29%. Almost invariably, portal hypertension either preceded or was
      diagnosed concurrently with pulmonary hypertension, favoring the hypothesis that
      in portal hypertension, the pulmonary vasculature may be exposed to vasoactive
      substances normally metabolized or produced by the diseased liver, possibly
      inducing vasoconstriction or direct toxic damage to the pulmonary arteries.
      Clinically, exertional dyspnea was the most frequent presenting symptom (81%);
      other symptoms, such as syncope, chest pain and fatigue, were present in less
      than 33%. An accentuated pulmonary component of the second heart sound (82%) and
      a systolic murmur (69%) were the most common physical findings. At least 75% of
      these patients had evidence of pulmonary hypertension on electrocardiography
      (right ventricular hypertrophy) or roentgenography (cardiomegaly or dilated main
      pulmonary arteries, or both). Hemodynamic findings included severe pulmonary
      hypertension (mean pulmonary artery pressure 59 +/- 19 mm Hg) with normal
      pulmonary capillary wedge pressure and cardiac output. Treatment was basically
      palliative and the mean and median survival times were 15 and 6 months,
      respectively. In brief, on the basis of clinical presentation and laboratory
      features, patients with combined primary pulmonary hypertension and portal
      hypertension seldom represent a diagnostic challenge. Further research is needed
      on treatment, which remains palliative. The survival rate is poor and worse than
      that seen in isolated primary pulmonary hypertension.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1991909
TI  - Mechanisms of angina pectoris in syndrome X.

PMID- 1991910
TI  - Syndrome X revisited.

PMID- 1991911
TI  - Atrial activation sequence during atrial flutter in the canine pericarditis model
      and its effects on the polarity of the flutter wave in the electrocardiogram.
AB  - Stable atrial flutter induced in both conscious and open chest states was studied
      in 30 mongrel dogs after production of sterile pericarditis. During the conscious
      state studies, induced atrial flutter (mean cycle length 128 +/- 15 ms) was
      always sustained greater than 15 min and was stable. Three types of flutter wave
      polarity were noted in electrocardiogram (ECG) lead II: positive in 16 dogs,
      negative in 3 and flat or slightly positive in 11. Sequential site atrial mapping
      during atrial flutter (mean cycle length 133 +/- 18 ms) in the open chest state
      showed either clockwise (18 dogs) or counterclockwise (12 dogs) circus movement
      in the right atrium. In 19 of 30 dogs, the circus movement clearly did not
      require any naturally existing anatomic obstacle; in 11, the orifice of the
      superior vena cava probably was also involved. Double potentials were recorded
      from the center of the reentrant circuit during atrial flutter, and fractionated
      electrograms were recorded from a pivot point of the reentrant wave front. A
      positive flutter wave in ECG lead II (12 dogs with counterclockwise circus
      movement) was associated with early activation of the Bachmann's bundle region
      compared with the posteroinferior left atrium and activation of the left atrium
      mainly in a superoinferior direction. A negative flutter was associated with the
      early activation of the posteroinferior left atrium compared with Bachmann's
      bundle and activation of a considerable portion of the left atrium in an
      inferosuperior direction. A flat or slightly positive flutter wave (14 of 18 with
      clockwise circus movement) was associated with activation of the left atrium
      almost simultaneously by two wave fronts coming from both these sites. In
      conclusion, atrial flutter in this dog model is due to circus movement in the
      right atrium, the center of which does not necessarily require an anatomic
      obstacle. Although atrial flutter is generated by circus movement in the right
      atrium, the flutter wave polarity in the ECG is determined primarily by the
      activation sequence of the left atrium.

PMID- 1991912
TI  - Transesophageal echocardiography is superior to transthoracic echocardiography in
      the diagnosis of sinus venosus atrial septal defect.
AB  - The purpose of this study was to compare transthoracic and transesophageal
      echocardiography in the diagnosis of various types of atrial septal defects.
      Forty-one adult patients with the clinical diagnosis of atrial septal defect were
      studied by transthoracic and transesophageal echocardiography (30 women, 11 men;
      18 to 81 years of age). Transthoracic echocardiography demonstrated the atrial
      septal defect in 33 patients (secundum type in 28, primum type in 3 and sinus
      venosus type in 2). Transesophageal echocardiography demonstrated the defect in
      all 41 patients. Thus, in 8 (20%) of 41 patients the atrial septal defect was
      demonstrated by transesophageal and not by transthoracic echocardiography. Six of
      the eight had a sinus venosus type atrial septal defect; the other two patients
      had a secundum atrial septal defect (one of these two had a technically poor
      transthoracic echocardiogram and the other had a small atrial septal defect).
      Transthoracic echocardiography, therefore, failed to demonstrate the sinus
      venosus defect in six (75%) of eight patients. An anomalous venous connection
      associated with the sinus venosus defect was visualized by transesophageal
      echocardiography in seven of the eight patients but was not seen on transthoracic
      echocardiography in any patient. Sinus venosus type atrial septal defects are
      frequently not visualized in adults by conventional transthoracic
      echocardiography. Transesophageal echocardiography is recommended when an atrial
      septal defect is clinically suspected but cannot be visualized by transthoracic
      echocardiography.

PMID- 1991913
TI  - Ureaplasma urealyticum chronic osteomyelitis in a patient with
      hypogammaglobulinemia.
AB  - Mycoplasma species are recognized as important pathogens in patients with
      hypogammaglobulinemia. In this article we describe, for the first time, a patient
      with hypogammaglobulinemia who developed osteomyelitis of the hip caused by
      Ureaplasma urealyticum. This article emphasizes the need for considering
      infection with Mycoplasma species in patients with antibody deficiency.

PMID- 1991914
TI  - Caffeine, a naturally occurring acaricide.
AB  - Since caffeine is a plant alkaloid that has been described as a naturally
      occurring insecticide, its acaricidal effect on Dermatophagoides pteronyssinus
      (Dp) was investigated. Twelve cultures were established by adding 30 Dp to 200 mg
      of Tetramin fish food and brewer's yeast (8:2 ratio); six cultures were treated
      with 20 mg of finely ground caffeine. All 12 cultures were incubated at 75%
      relative humidity, 25 degrees C, and observed during 8 weeks. Live mites were
      then counted under a stereoscope, cultures were extracted, and supernatants were
      analyzed for Der p I and Der f I allergen content with a two-site monoclonal RIA.
      Live mite counts in untreated cultures varied from 146 to 274 (215 +/- 47.1), and
      in caffeine-treated cultures from 0 to 3 (1 +/- 1.2; p less than or equal to
      0.0001). Der p I concentrations in untreated cultures varied from 588 to 9000
      ng/gm (3138.3 +/- 2990.8 ng/gm), and in caffeine-treated cultures from 52 to 117
      ng/gm (78 +/- 23.8 ng/gm; p less than or equal to 0.01). Der p I was not detected
      in the food media or caffeine; Der f I was not detected in any of the cultures.
      Results demonstrate that caffeine inhibits mite growth and allergen production.

PMID- 1991915
TI  - Special requirements for residency training in diagnostic laboratory immunology.

PMID- 1991916
TI  - Cross-reactivity between latex and banana.

PMID- 1991918
TI  - Allergists and immunologists professional liability insurance.

PMID- 1991917
TI  - Comparison of the ACAREX test with monoclonal antibodies for the quantification
      of mite allergens.

PMID- 1991919
TI  - Some limitations of double-blind, placebo-controlled food challenges in young
      children.

PMID- 1991920
TI  - Systemic cold urticaria (atypical acquired cold urticaria)

PMID- 1991921
TI  - Food-dependent, exercise-induced anaphylaxis: a study on 11 Japanese cases.
AB  - Eleven patients with food-dependent, exercise-induced anaphylaxis were studied.
      Seven patients experienced anaphylactic symptoms only after eating certain foods,
      such as shellfish, wheat, and grape before exercise. In the remaining four
      patients, no specific food could be identified, but the act of eating itself
      predisposed to anaphylaxis. Their anaphylactic symptoms were all clearly
      distinguished from cholinergic urticaria by history. Patients who developed
      anaphylactic symptoms before 20 years of age (N = 7) were atopic themselves or
      had atopic first-degree relatives. Six patients had increased serum IgE levels,
      and IgE antibodies against the causative food allergens were detected by the skin
      prick test or RAST in four cases. In contrast, patients who developed the
      symptoms after 30 years of age (N = 4) appeared to have a less atopic background,
      and IgE levels were within normal range except in one case. Three of four
      patients in the latter group developed symptoms after ingesting food made of
      wheat followed by exercise. All patients were sensitive to wheat as determined by
      the skin prick test. In six of 11 patients, a considerable rise in plasma
      histamine concentration was observed after exercise challenge with treadmill
      alone, and food intake followed by exercise induced a further increase in one
      patient.

PMID- 1991922
TI  - Short-term effect of solidified benzyl benzoate on mite-allergen concentrations
      in house dust.
AB  - The effect of solidified benzyl benzoate (bb) foam and powder on concentrations
      of the major allergens of Dermatophagoides pteronyssinus (Der p I) and D. farinae
      (Der f I) in dust samples from mattresses and carpets in 22 households was
      investigated in a randomized, double-blind, placebo-controlled trial. All houses
      had been demonstrated to have significant (greater than or equal to 2000 ng/gm of
      dust) mite-allergen concentrations on mattresses. Dust samples were collected
      from mattresses and carpets before treatment and on days 10, 30, and 60 after the
      first treatment. There was a second application on day 10. Der p I and Der f I
      were determined by a sandwich-type ELISA with monoclonal noncross-reacting
      antibodies to Der p I and polyclonal monospecific antibodies to Der f I. There
      was a significant reduction of mite allergens in mattresses and carpets within
      both bb-treated and control groups, but only the results on carpets of the bb
      treated group were significantly different from results of the control group on
      days 30 and 60 (p less than 0.05).

PMID- 1991923
TI  - Serum IgE and IgG to formaldehyde-human serum albumin: lack of relation to
      gaseous formaldehyde exposure and symptoms.
AB  - Fifty-five subjects were studied to determine if the presence of IgE or IgG
      antibodies to formaldehyde (F)-human serum albumin (HSA) was associated with
      exposure to gaseous F or with respiratory or conjunctival symptoms from such
      exposure. The study population included cohorts exposed to F in the workplace,
      smokers, and normal subjects. IgE antibody specific for F-HSA was detected by
      ELISA in three subjects; immediate-type skin testing was negative in two of these
      subjects, and not interpretable because of dermatographism in one subject. One of
      these subjects had a history of respiratory symptoms when the subject was working
      in a histology laboratory that contained ambient F and xylene; a respiratory
      challenge with F at concentrations of up to 2 ppm failed to produce respiratory
      symptoms or significant changes in pulmonary function. Serum from the three
      subjects with IgE to F-HSA by ELISA failed to passively transfer skin reactivity
      to F-HSA to rhesus monkey recipients. These three subjects and two other subjects
      had IgG to F-HSA by ELISA, although this was of generally low titer. We could not
      define a relationship between the presence of antibodies and (1) a history of F
      exposure or (2) a history of adverse respiratory or conjunctival symptoms from F.
      This study is a continuum of 5 years of study in our laboratory attempting to
      define allergy to gaseous F, and the current study does not support an
      immunologic basis for respiratory or conjunctival symptoms from gaseous F
      exposure. Based on the findings of this and our other studies, it is possible
      that clinical IgE-mediated allergy to gaseous F does not exist, or if it does
      exist, it is extremely rare.

PMID- 1991924
TI  - Effect of steroids on immunoglobulin-induced eosinophil degranulation.
AB  - Because glucocorticoids are a mainstay in the treatment of asthma and other
      allergic diseases, we tested the effect of various steroid hormones on secretory
      IgA- and IgG-induced eosinophil degranulation in vitro. Human normodense
      eosinophils were purified by discontinuous Percoll density gradient, and
      hypodense eosinophils were obtained by culture of normodense cells with
      recombinant human interleukin (rIL)-5. Eosinophils were incubated with various
      steroids, including dexamethasone, hydrocortisone, methylprednisolone, estradiol,
      or dihydrotestosterone at concentrations from 10(-9) to 10(-4) mol/L. Sepharose
      4B beads coupled to ovalbumin, secretory IgA, or IgG were added as targets of
      degranulation and incubated at 37 degrees C for 4 hours. In some experiments, rIL
      5 was added to eosinophils before addition of beads to activate the cells. The
      release of eosinophil-derived neurotoxin was measured by radioimmunoassay as an
      index of degranulation. Dexamethasone (10(-9) to 10(-4) mol/L), hydrocortisone
      (10(-9) to 10(-4) mol/L), estradiol (10(-9) to 10(-7) mol/L), and
      dihydrotestosterone (10(-9) to 10(-4) mol/L) had no effect on normodense
      eosinophil degranulation. Methylprednisolone, 10(-5) mol/L, inhibited
      degranulation of normodense eosinophils up to 20%, whereas 10(-4) mol/L inhibited
      degranulation of hypodense eosinophils, up to 30%. Overall, no difference in
      inhibition by steroids was observed between normodense and hypodense eosinophils.
      rIL-5 enhanced immunoglobulin-induced eosinophil degranulation, but this effect
      of rIL-5 was not blocked by any of the steroids tested. These results suggest
      that eosinophil degranulation and rIL-5-mediated eosinophil activation are not
      direct targets of glucocorticoids and that the beneficial effects of
      glucocorticoids on allergic inflammation in vivo are not likely due to direct
      effects on eosinophil degranulation.

PMID- 1991925
TI  - Sensitization to aztreonam and cross-reactivity with other beta-lactam
      antibiotics in high-risk patients with cystic fibrosis.
AB  - The immunogenicity, allergenicity, and cross-reactivity of aztreonam were
      investigated in 21 patients with cystic fibrosis (CF) (aged 5 to 39 years) with
      well-documented histories of allergic systemic reactions (SRs) to penicillin
      and/or cephalosporin antipseudomonal beta-lactam antibiotics (BLAs). Skin tests
      (STs) with penicilloyl-polylysine (PPL), penicillin minor determinant mixture,
      and antipseudomonal BLA were positive in 19 patients (90%). The BLA causing the
      most recent allergic reaction, minor determinant mixture, or PPL, was positive in
      89%, 53%, and 32% of ST-positive patients, respectively. Serum PPL-specific IgE
      antibodies were not detectable, although PPL-specific IgG antibodies were found
      in 64% of patients tested. STs to aztreonam reagents were performed and were
      initially negative in 20 patients. One patient was ST positive to the polylysine
      conjugate of hydrolyzed aztreonam (SQ 27629), despite no prior exposure to
      aztreonam, and was not treated. Of 20 patients treated with aztreonam, four were
      demonstrated to be sensitized by exposure (one had an SR during initial treatment
      course, two had SRs on reexposure, and one patient was asymptomatic after
      intravenous desensitization) by positive aztreonam reagent skin responses on
      repeat testing. Aztreonyl-specific IgE and IgG serum antibodies were not detected
      in any patients, including patients with allergic reactions to aztreonam. Thus,
      aztreonam is generally well tolerated in high-risk patients with CF allergic to
      other BLAs and appears to have reduced immunogenicity by serologic testing.
      However, caution should be exercised with aztreonam in BLA-allergic patients with
      CF in light of 5% preexisting ST cross-reactivity and 20% sensitization rates
      found in this study.

PMID- 1991926
TI  - The effect of the oral leukotriene antagonist, ICI 204,219, on leukotriene D4 and
      histamine-induced cutaneous vascular reactions in man.
AB  - Eighteen normal male subjects were recruited for a double-blind, placebo
      controlled, randomized, two-period crossover study to determine the effects of a
      new, potent, highly selective, oral peptide leukotriene antagonist (ICI 204,219)
      on cutaneous vasculature. Skin testing for leukotriene D4 (LTD4) and histamine
      was performed at three different time intervals after receiving ICI 204,219 or
      placebo. The LTD4 threshold dose responses were recorded in duplicate to verify
      reproducibility. These data confirm known remarkable dose-response variation of
      cutaneous vascular reactions to LTD4 since some subjects reacted to a dose as low
      as 0.001 fmol. Twelve subjects (67%) demonstrated a more than one-half log
      increase in their threshold response after receiving ICI 204,219. Five of these
      12 subjects (28%) had greater than 1 log-dose response after ICI 204,219. Two of
      these subjects (11.1%) had a 5 or 10 log increase in their threshold response
      after receiving ICI 204,219. Given the role of leukotrienes as potentially
      important mediators in immediate-type reactions, our results raise the
      possibility for additional investigation of the antagonistic effect of ICI
      204,219 in nonallergic and allergic cutaneous diseases.

PMID- 1991927
TI  - Adequacy of zinc recommendations questioned.

PMID- 1991928
TI  - Five Fs focus on heart healthy recovery after coronary bypass surgery.

PMID- 1991929
TI  - Reversing heart disease through diet, exercise, and stress management: an
      interview with Dean Ornish. Interview by Elaine R Monsen.

PMID- 1991930
TI  - Contributions of specific foods to absolute intake and between-person variation
      of nutrient consumption.
AB  - Contributions of specific foods and supplements to absolute intake and between
      person variance in consumption of 19 macronutrients, vitamins, and minerals were
      examined using dietary records of all foods consumed over 4 weeks by 194 US
      nurses aged 34 to 59 years. To measure their contribution to absolute nutrient
      intake, we ranked foods by the percentage of the population's total nutrient
      intake that they provided. To assess the degree to which differences in
      consumption of specific foods explain between-person variability in nutrient
      intake, we re-ranked the 20 foods contributing most to absolute intake of each
      nutrient as independent variables in stepwise multiple regression analyses
      predicting total intake of that nutrient. The increase in percentage of the
      variance in nutrient intake explained by the addition of a food to the
      progressively larger list of food items (expressed as the cumulative R2) served
      as the measure of contribution to variation in intake. Some nutrients had only a
      few major sources and were assessed relatively well by a small number of foods.
      For preformed vitamin A without supplements, 10 foods accounted for 82% of the
      absolute intake and 98% of total variance. The corresponding percentages for
      absolute intake and total variance, respectively, were 66% and 94% for beta
      carotene; 77% and 92% for cholesterol; and 71% and 95% for vitamin C without
      supplements. In contrast, 20 foods accounted for only 54% of the absolute intake
      and 73% of the variance for total energy intake; 58% and 89%, respectively, for
      total carbohydrates; and 59% and 84%, respectively, for potassium.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1991931
TI  - Total diet study nutritional elements, 1982-1989.
AB  - Daily intakes of sodium, potassium, calcium, phosphorus, magnesium, iron, zinc,
      selenium, iodine, copper, and manganese for eight age-sex groups are presented
      for 1982 to 1989. Compared with the intakes recommended by the National Academy
      of Sciences, sodium intakes (which did not include discretionary salt) exceeded
      the estimated minimum requirement; intakes of potassium, phosphorus, selenium,
      and iodine were adequate for all groups; and copper intakes were low (less than
      80% of the suggested intake) for all groups. In addition, calcium, magnesium,
      iron, and manganese were low in the diets of teenage girls; calcium, magnesium,
      and iron were low in the diets of adult women; calcium, magnesium, and zinc were
      low in the diets of older women; calcium and zinc were low in the diets of 2-year
      olds; and magnesium was low in the diets of teenage boys and older men. The
      primary food group source for each element was dairy products for potassium,
      calcium, phosphorus, magnesium, and iodine; grain products for sodium, iron, and
      manganese; and animal flesh for zinc, selenium, and copper.

PMID- 1991932
TI  - Productivity in nutrition programs for the elderly that utilize an assembly-serve
      production system.
AB  - Observations of labor activities of workers performing foodservice functions were
      made in eight senior centers at 5-minute intervals for 3 consecutive days. On
      site preparation was limited to rethermalization of frozen entrees and portioning
      of bulk-delivered items. Time spent was assigned or allocated to either
      congregate or home-delivered meal service on the basis of number of meals served.
      Time in each component of direct work, indirect work, and delay was divided by
      meals served to provide the productivity ratio, labor minutes per meal.
      Comparisons were also made on the basis of number of meals served. An average of
      12.78 minutes per meal was used to serve congregate meals and 21.05 minutes per
      meal for home-delivered meals. Two of the eight centers differed significantly in
      time used for direct work and total work to serve congregate-meal participants.
      There was no difference between centers in time used to serve homebound clients.
      The number of meals served did not influence productivity for either meal service
      site. These findings establish baseline data for the amount of time needed in one
      production system to serve meals to center participants and homebound clients.
      Managers of senior centers can use information about this food production and
      delivery system to make decisions about the most cost-effective method to provide
      meals.

PMID- 1991933
TI  - Physicians' perspectives on cholesterol and heart disease.
AB  - In early spring of 1988, questionnaires were mailed to 4,000 Midwestern
      physicians to survey their attitudes and practices regarding elevated serum
      cholesterol and their use of referrals for nutrition counseling; 633 physicians
      responded. Sixty-eight percent of the physicians thought that reducing high serum
      cholesterol levels would substantially affect heart disease; however, physicians
      attributed considerably less preventive value to reducing the cholesterol level
      than to reducing blood pressure (80.3%) or ceasing smoking (90.0%). The range of
      serum cholesterol for which diet therapy was most frequently initiated was 5.70
      to 6.20 mmol/L. The most frequent range for initiation of drug therapy was 7.80
      to 8.25 mmol/L. The physicians reported that although their medical school
      training did not prepare them adequately for providing diet counseling, they did
      feel prepared to provide, and were successful in, counseling on diet
      modifications for reducing serum cholesterol. Few (10%) of the total sample
      reported having registered dietitians available for dietary counseling, and most
      (88.8%) believed that it is the physician's responsibility to provide such
      counseling. Although the low response rate limits the conclusions of the survey,
      it is likely that those physicians most interested in the topic responded. We
      conclude that registered dietitians should explore the need for their special
      services further. More aggressive marketing of dietetic services could benefit
      both physicians and patients in the campaign to reduce serum cholesterol.

PMID- 1991935
TI  - Food records: a predictor and modifier of weight change in a long-term weight
      loss program.
AB  - Overriding concerns about the accuracy of self-reported food records have
      overshadowed discussion of their practical value as a self-management,
      intervention tool. This study examined the relationship between keeping food
      records and subsequent weight loss in a large-scale, conservative weight loss
      program. Keeping food records was a better predictor of weight loss than were
      baseline body mass index, exercise, and age. Monthly as well as cumulative weight
      loss was directly related to the number of days in which food records were kept.
      The strong, linear relationship between food record patterns and weight loss
      suggests that in spite of legitimate concern about the accuracy and
      representativeness of self-reported food records, they have considerable power as
      a predictor of success in achieving weight loss.

PMID- 1991934
TI  - Nutrition management for individuals with noninsulin-dependent diabetes mellitus
      in the 1990s: a review by the Diabetes Care and Education dietetic practice
      group.
AB  - Noninsulin-dependent diabetes mellitus (NIDDM), or Type II diabetes, is
      characterized by two primary defects: insulin resistance and insulin secretion.
      The two major goals of management of NIDDM are to achieve near normal metabolic
      control and to prevent/delay the microvascular and macrovascular complications of
      diabetes. Nutrition, exercise, and, if necessary, medication are the three
      primary treatment modalities used in NIDDM. Treatment regimens need to be
      individualized and developed with consideration for diabetes management goals and
      quality-of-life issues. Lean individuals with NIDDM should be encouraged to
      maintain their body weight and modify food composition and eating pattern to
      minimize glucose excursions. The primary treatment goal for an obese individual
      with NIDDM is weight loss. The process of teaching nutrition and meal planning
      involves developing a cooperative alliance, gathering information, setting
      realistic goals, intervention, and maintaining change. Nutrition intervention
      involves providing information in stages, beginning with "survival skill"
      information and progressing to in-depth information. The dietitian's
      responsibility is to promote continuity of learning by introducing new ideas and
      concepts and altering the learning environment. Dietitians can expand their role
      in the 1990s to that of a diabetes educator taking a leadership role to ensure
      that the individual with NIDDM receives comprehensive and individualized care.

PMID- 1991936
TI  - Nutritional complications and incidence of malnutrition among AIDS patients.

PMID- 1991937
TI  - Nutrition activities in university-based fitness programs.

PMID- 1991938
TI  - Incidence of nasoduodenal tube occlusion and patient removal of tubes: a
      prospective study.

PMID- 1991939
TI  - Nutrition education in the clinical setting for medical residents.

PMID- 1991940
TI  - A survey of pocket computer use for nutrition services.

PMID- 1991941
TI  - Resetting the American table--creating a new alliance of taste and health.

PMID- 1991942
TI  - Diagnosis of illness presentation in the elderly.
AB  - In the standard medical model of diagnosis, there is a 1:1 correspondence between
      clinical symptoms and signs and a pathological disease process. However, it is
      believed that this model does not accurately define many illness presentations in
      elderly patients. The frequency with which the medical model is diagnostically
      accurate, and the other models that might more effectively diagnose geriatric
      illness, are unknown. This study was designed to ascertain the frequency with
      which the medical model of diagnosis pertains in a clinical population of older
      adults and to develop and validate alternative models for diagnosis of illness
      presentation in this population. Using a retrospective chart review (n = 86) and
      a prospective validation in a second sample (n = 56) of geriatric assessment
      clinic patients, it was found that the medical model of illness fit less than
      half of the patients. To describe the illness presentations of the remaining
      patients, four new diagnostic models of illness presentation were identified
      which incorporate comorbidity, functional, and psychosocial factors. Use of these
      new models along with the medical model of illness diagnosis may assist in more
      accurate and complete diagnosis in elderly patients and enhance teaching of
      effective diagnosis in geriatric medicine.

PMID- 1991943
TI  - Comorbid psychiatric disorders in elderly medical patients: a 1-year prospective
      study.
AB  - Cross-sectional studies have revealed a high prevalence of comorbid psychological
      problems among geriatric medical patients, a low rate of detection by primary
      care professionals, and greater psychosocial dysfunction and poorer physical
      health associated with comorbidity. Less is known about the course and impact of
      psychiatric comorbidity. Psychiatric status, physical health status, psychosocial
      functioning, and health care utilization for a sample of geriatric patients (n =
      102) were assessed on admission to a medical hospital and again one year later.
      Results revealed a very stable and high prevalence of comorbid psychological
      problems, especially depression, a low rate of treatment by mental health
      professionals, greater physical impairment consistently associated with
      psychiatric comorbidity, but few health care utilization differences. A closer
      look at depression revealed that it typically began in late life and did not
      readily resolve.

PMID- 1991944
TI  - Nursing home patients transferred by ambulance to a VA emergency department.
AB  - Nursing home residents are frequently transferred to hospital emergency
      departments. Delayed transfer may lead to poor outcomes. However, inappropriate
      transfer of the frail elderly may cause social and financial problems. We
      prospectively evaluated 221 consecutive ambulance transfers from community
      nursing homes to a VA emergency department. The objectives of the study were to
      describe the process and outcomes of transferred patients and to determine if
      alternative interventions were feasible. The results indicate that the problems
      of nearly half the study group could have been treated at the nursing home by a
      visiting physician with minimal medical equipment. Those admitted to the hospital
      (52%) were seriously ill, had prolonged lengths of stay (23.6 days), and had a
      high mortality rate (11%). Complex issues of physician reimbursement, proprietary
      nursing home budgeting, and day-to-day expediency appear to be involved in
      decisions to transport patients by ambulance to VA emergency departments.

PMID- 1991945
TI  - Is the recommended daily allowance for vitamin D too low for the homebound
      elderly?
AB  - A population of sunlight-deprived elderly was studied to determine the daily
      intake of vitamin D and whether dietary intake was sufficient to maintain a
      normal vitamin D status. Twenty-two subjects over 65 years old with serum
      creatinine less than 180 mumols/L and confined indoors for more than 6 months
      were chosen from the community and a nursing home in Southeast Baltimore. Three
      day food records were obtained along with serum levels of 25-hydroxyvitamin D (25
      OHD), 1,25-dihydroxyvitamin D (1,25-(OH)2 D), and intact parathyroid hormone
      (PTH). The mean daily vitamin D intake was over twofold greater than the adult
      Recommended Daily Allowance (RDA) of 200 IU. The mean 25-OHD level was 40 nmol/L
      (normal 25-138 nmol/L) with seven patients less than 25 nmol/L. Of these
      participants with 25-OHD values less than 25 nmol/L, the mean vitamin D intake
      was 467 IU (range 36-1096 IU). We conclude that the current RDA seems inadequate
      for many older individuals who do not get sun exposure. This particular
      population of elderly is at risk to develop vitamin D deficiency and the
      associated complications.

PMID- 1991946
TI  - The timed "Up & Go": a test of basic functional mobility for frail elderly
      persons.
AB  - This study evaluated a modified, timed version of the "Get-Up and Go" Test
      (Mathias et al, 1986) in 60 patients referred to a Geriatric Day Hospital (mean
      age 79.5 years). The patient is observed and timed while he rises from an arm
      chair, walks 3 meters, turns, walks back, and sits down again. The results
      indicate that the time score is (1) reliable (inter-rater and intra-rater); (2)
      correlates well with log-transformed scores on the Berg Balance Scale (r = 
      0.81), gait speed (r = -0.61) and Barthel Index of ADL (r = -0.78); and (3)
      appears to predict the patient's ability to go outside alone safely. These data
      suggest that the timed "Up & Go" test is a reliable and valid test for
      quantifying functional mobility that may also be useful in following clinical
      change over time. The test is quick, requires no special equipment or training,
      and is easily included as part of the routine medical examination.

PMID- 1991947
TI  - Mini-Mental State exam scores vary with education in blacks and whites.
AB  - Previous studies have suggested that education and race may affect performance on
      standardized mental status tests. In order to more clearly define these
      relationships, a prospective longitudinal study was devised to answer two
      questions: (1) whether race or level of education affects scores on the Mini
      Mental State (MMS) exam in non-demented people and (2) what numerical cutpoints
      maximize the sensitivity and specificity of utilizing the MMS to help diagnose
      dementia in blacks of varying educational attainment. A total of 100 white and
      258 black individuals, recruited from two city hospital primary care geriatric
      clinics, were evaluated and subsequently followed longitudinally over a 2 1/2
      year period in order to assess accurately the presence or absence of dementia. In
      the non-demented, total MMS scores and performance on each item of the MMS were
      analyzed, revealing that people with an 8th grade or less education consistently
      had significantly (P less than .01) worse results than the better educated (9th
      grade or better) on borough, attention items, recall of table and dog, copying,
      sentence writing, phrase repeating, and total score. Furthermore, a total of 25%
      of the lower education group had an MMS score in the 18-23 range, traditionally
      thought to suggest dementia. There were no consistently significant differences
      between blacks and whites of equal education. In the better educated groups,
      using a score of 23 or less to define dementia maximizes the sensitivity and
      specificity of using the MMS in this diagnosis at 93% and 100%, respectively. In
      the lower education group, using 17 or less to define dementia maximizes
      sensitivity and specificity at 81% and 100%, respectively.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1991948
TI  - Physician practices in the diagnosis of dementing disorders.
AB  - Because there are both treatable and untreatable causes of dementia, the
      physician's ability to conduct (or refer a patient for) a differential diagnosis
      could have a profound effect on health outcomes for patients and on health care
      costs. This study was undertaken to assess physician practices with regard to the
      diagnosis of dementing disorders. Data from 53 physicians (a response rate of
      48%) in several specialties were obtained from a self-administered mail
      questionnaire. Results indicate that the majority of physicians provided history
      taking, physical examination, and neurological examination. Physicians were more
      likely to refer patients for psychiatric and neuropsychological examinations than
      to provide these services themselves. The results also point to deficiencies in
      two key areas: the use of formal, published diagnostic criteria, and the use of
      mental status and cognitive function tests. Over 75% of physicians surveyed did
      not use either DSM-III or NINCDS-ADRDA diagnostic criteria, and 42% of physicians
      did not provide any mental status tests themselves. The need for continuing
      education to close knowledge gaps is emphasized.

PMID- 1991949
TI  - Hyposomatomedinemia in men with post-poliomyelitis syndrome.
AB  - The age of onset of the post-poliomyelitis syndrome (PPS) coincides with the
      tendency for declining activity of the growth hormone/somatomedin C (GH/SmC)
      axis. The normal plasma SmC range in men before the age of 40 is 0.50 to 1.50
      units/mL. After age 40 about 30% of men have a plasma SmC level below 0.35
      units/mL, signifying no detectable spontaneous GH secretory pulses. Because the
      GH/SmC axis stimulates DNA, RNA, and protein synthesis in muscle cells and
      increases their size and number, a deficiency of the GH/SmC axis could
      theoretically contribute as a secondary factor to the occurrence or severity of
      the PPS. Accordingly, the authors measured the plasma SmC level in 10 men with
      PPS, ages 35 to 63, and in 94 healthy men of similar age. In the PPS men, 100% of
      the values were less than or equal to 0.40 units/mL, and 90% were less than or
      equal to 0.35 units/mL. The corresponding proportions in the healthy men were 40%
      and 27%. Analysis of variance including age as a factor showed SmC to be
      significantly lower in the PPS men than in the healthy men. In an additional
      comparison, totally immobile nursing home men did not have lowered SmC values. In
      fact their SmC values were slightly higher than those of healthy men of similar
      age. The data revealed a new biochemical feature of PPS, hyposomatomedinemia,
      which might play a contributory role in the pathogenesis of the syndrome.

PMID- 1991950
TI  - The metabolic effects of calcium supplementation in the elderly.
AB  - Because the value of calcium supplementation in age-related bone loss is
      controversial, we conducted a study to examine the effects of six months of
      calcium supplementation on parathyroid hormone (PTH) and other indices of bone
      metabolism. Calcium carbonate (1.2 grams elemental calcium/day) or placebo was
      administered for 6 months to a group of 42 healthy, ambulatory men and women with
      a mean age of 71. Fasting blood samples and 2-hour urine collections were
      performed at baseline and at 1 and 6 months. The decline in serum PTH levels from
      baseline in the calcium-supplemented group was significant in comparison with the
      placebo group changes (for the calcium group: 40.9 pg/mL at baseline to 34.0
      pg/mL at 1 month and 33.2 at 6 months). This drop in PTH was associated with a
      decline in 1,25 OH-Vitamin D levels from a mean of 38.3 pg/mL to 30.4 pg/mL at 1
      month and 31.9 at 6 months. During calcium supplementation, no changes were
      observed in serum bone Gla protein values. A decline in urinary hydroxyproline
      excretion was observed at 6 months, but this did not reach significant levels.
      The present study demonstrates suppression of PTH levels with calcium
      supplementation, an effect which lasts at least 6 months. This change was
      accompanied by a decrease in serum 1,25 OH-Vitamin D. The lack of significant
      changes in either serum bone gla protein or urine hydroxyproline excretion fails
      to support any significant change in bone turnover occurring with this decrease
      in PTH.

PMID- 1991951
TI  - Falls in the elderly: reliability of a classification system.
AB  - To determine risk factors for falls, previous studies have classified falls
      according to the contribution of factors both intrinsic and extrinsic to the
      host. Due partly to the lack of operational definitions and the absence of
      information on reliability, no consensus on classification has been reached.
      Consequently, in a 3-year prospective study of falls occurring in a probability
      sample of community-dwelling elderly (n = 1,358), a fall classification system
      was developed and tested for interrater reliability. The 366 falls in the first
      year of the study were independently classified by two reviewers on the basis of
      a narrative description and structured interview. The falls in the four major
      categories of the classification system included: falls related to extrinsic
      factors (55%), falls related to intrinsic factors (39%), falls from a non-bipedal
      stance (8%) and unclassified falls (7%). The interrater reliability for the four
      major categories was 89.9% with a kappa of 0.828. The system provides operational
      definitions for types of falls and a reliable and flexible method for classifying
      falls in the elderly.

PMID- 1991952
TI  - Occult infection of hip prosthesis: sonographic evaluation.

PMID- 1991953
TI  - Rocky Mountain spotted fever in the elderly.

PMID- 1991954
TI  - Word deafness mistaken for Alzheimer's disease: differential characteristics.

PMID- 1991955
TI  - Resolving complexity in geriatrics.

PMID- 1991956
TI  - Hospital-associated deconditioning and dysfunction.

PMID- 1991957
TI  - Are restraints all bad?

PMID- 1991958
TI  - Aeromonas hydrophila diarrhea.

PMID- 1991959
TI  - Diabetes and cognition.

PMID- 1991960
TI  - The role of polymorphic amino acids of the MHC molecule in the selection of the T
      cell repertoire.
AB  - Allelic variants of MHC molecules expressed on cells of the thymus affect the
      selection and the specificity of the T cell repertoire. The selection is based on
      either the direct recognition by the TCR of the MHC molecules, or the recognition
      of a complex determinant formed by self-peptides bound to MHC molecules. In an
      analysis of the T cell repertoire in bone marrow chimeras that express allelic
      forms of MHC class II molecules in the thymus epithelium, we find that amino acid
      substitutions that are predicted to affect peptide binding influence the
      selection of the T cell repertoire during thymic selection.

PMID- 1991961
TI  - Retroviral transduction of protein kinase C-gamma into cytotoxic T lymphocyte
      clones leads to immortalization with retention of specific function.
AB  - The molecular pathways that are responsible for delivering the proliferative
      signals from the cell surface to the nucleus in T lymphocytes are still
      unresolved, but recent data implicates protein kinase C (PKC) involvement in the
      TCR signaling pathway. To further address the role of PKC in T cell activation,
      the effects of high level expression of the PKC-gamma isoenzyme in murine CTL
      clones were examined. Unlike the parental cells that required periodic Ag
      stimulation for cell activation and growth, cells expressing a retrovirally
      transduced PKC-gamma gene propagated in culture independent of the need for Ag
      stimulation, although maintaining identical functional specificity to the
      parental CTL. Constitutive PKC-gamma expression may therefore mimic physiologic
      PKC activation, thereby abrogating the requirement for TCR-Ag interaction in T
      cell activation.

PMID- 1991962
TI  - Dexamethasone inhibits the induction of monocyte chemotactic-activating factor
      production by IL-1 or tumor necrosis factor.
AB  - Recently purified and molecularly cloned monocyte chemotactic and activating
      factor (MCAF) may play a major role in recruiting and activating monocytes in the
      inflammatory process. We examined the effects of a potent anti-inflammatory
      agent, dexamethasone (DXS), on the production of this factor. Over a wide range
      of concentrations (10(-5) to 10(-8) M), DXS inhibited the production of MCAF at
      the mRNA and protein level in a human fibrosarcoma cell line, which was
      stimulated with either IL-1 or TNF-alpha. We examined the turn-over of
      synthesized MCAF mRNA that showed DXS decreased the stability of MCAF mRNA.
      Furthermore, the addition of actinomycin D and cycloheximide abolished this
      effect of DXS, indicating that de novo mRNA and protein synthesis were required
      for this process. In addition, a nuclear run-off analysis revealed that DXS also
      inhibited the transcription of IL-1- or TNF-activated MCAF genes. Therefore, both
      the destabilization of MCAF mRNA and the inhibition of transcription of the gene
      contribute to the decrease in the MCAF mRNA steady state level by DXS.

PMID- 1991963
TI  - Properties of murine antibodies from different V region families specific for
      bromelain-treated mouse erythrocytes.
AB  - We have analyzed the combining site diversity of murine antibodies reactive with
      bromelain-treated mouse RBC (BrMRBC) in B10.A mice. Although several VH and V
      kappa genes are used to generate antibodies of this specificity, two combinations
      account for more than 80% of the repertoire from the spleen: VH11/V kappa 9 and
      VH12/V kappa 4. Antibodies representing these two predominant groups were found
      to correspond to two previously reported distinct cross-reactive Id families
      accounting for most of the anti-BrMRBC reactivity in several strains of mice. mAb
      of the VH11/V kappa 9 type bound the haptens trimethyl-ammonium and
      phosphorylcholine much more avidly (approximately 1000 fold) than did the VH12/V
      kappa 4 type antibodies. Both of these haptens represent constituents of
      phosphatidylcholine, which BrMRBC-specific antibodies are reported to bind.
      Despite this differential reactivity, members of both the VH11/V kappa 9 and
      VH12/V kappa 4 antibody groups lysed BrMRBC with similar efficiencies. These data
      suggest that the two major classes of BrMRBC-specific antibodies have at least
      partially different specificities and imply that the events that lead to their
      high frequencies in the CD5+ repertoire may result from different selective
      forces.

PMID- 1991964
TI  - Analysis of the binding of C-reactive protein to chromatin subunits.
AB  - C-reactive protein (CRP) is an acute phase serum protein in man. The functional
      activities of CRP, like Ig, include complement activation and enhancement of
      phagocytosis. CRP binding to several substrates, including phosphocholine,
      individual denatured histones, and chromatin, has been demonstrated. We
      previously demonstrated that CRP binding to chromatin is dependent on the
      presence of histone H1, despite the fact that CRP binds to purified individual
      histones H2A and H2B, as well as to H1. In this report we examined the binding of
      CRP to native sub-nucleosomal chromatin fragments. CRP binding to the H2A-H2B
      dimer and (H3-H4)2 tetramer was demonstrated and these reactions were inhibited
      by phosphocholine. However, no binding to the subnucleosome complexes (H2A-H2B)
      DNA and (H3-H4)2-DNA was seen. Similarly, CRP binding to H1 was eliminated when
      H1 was reconstituted with DNA. The reconstitution of H1-depleted chromatin with
      H1 restored CRP binding. CRP binding to nucleosome core particles, as previously
      demonstrated by others, was confirmed. Therefore, the interaction of CRP with
      individual core histones does not appear to be responsible for the binding of CRP
      to native chromatin. However, binding to core particles could be mediated by
      differentially exposed determinants on H2A and H2B.

PMID- 1991965
TI  - Exogenous C1q reconstitutes a secondary deficiency of C5-deficient AKR mouse
      macrophages for FcR-dependent cellular cytotoxicity and phagocytosis.
AB  - Studies originally designed to assess the putative role of endogenous C5 in
      macrophage activation for antibody-dependent cellular cytotoxicity (ADCC) yielded
      unanticipated results. Resident and inflammatory peritoneal macrophages from C5
      deficient AKR mice were found to have significantly lower capacity for FcR
      dependent ADCC activation and phagocytosis of IgG-opsonized SRBC targets than did
      C5-competent C3HeB/FeJ (C3H) mice. Reconstitution of the ADCC response of AKR
      macrophages was accomplished initially with C5-sufficient C3H mouse serum, which
      suggested that endogenous C5 may be required for ADCC activation. However,
      further investigation largely eliminated C5 involvement in that a heat-labile
      component of C5-deficient AKR serum was shown to be active in the reconstitution
      of ADCC activation of AKR macrophages. Macrophages from AKR mice were found to
      have significantly lower levels of C1q mRNA synthesis, endogenous C1q levels, and
      C1q secretion than did C3H mouse macrophages as determined by Northern blot,
      Western blot, and presynthetic radiolabeling analysis, respectively. The addition
      of purified exogenous C1q to IgG-opsonized SRBC targets fully reconstituted ADCC
      activation for AKR inflammatory peritoneal macrophages to levels of normally FcR
      responsive C3H macrophages. Similarly, exogenous C1q augmented FcR-dependent
      phagocytosis of AKR macrophages but had no effect on macrophages from responsive
      C3H mice. Our results indicate that AKR mice have a deficiency for FcR-dependent
      cellular cytotoxicity and phagocytosis that is related to their low potential for
      C1q synthesis and secretion rather than to their established genetic deficiency
      for C5 synthesis. We tentatively conclude that endogenous C1q is required as an
      accessory molecule for macrophage FcR-dependent effector functions and that C5 is
      not a prerequisite for ADCC activation.

PMID- 1991966
TI  - Evidence for functional heterogeneity in IgG Fc-binding proteins associated with
      group A streptococci.
AB  - A number of group A streptococcal isolates have been compared for their nonimmune
      reactivity with each human IgG subclass, and rabbit, pig, or horse IgG. The
      results obtained demonstrate considerable heterogeneity in the expression of type
      II IgG-binding proteins among and within group A isolates. Extraction and
      analysis of type II IgG-binding proteins from selected strains demonstrate the
      existence of five functionally distinct IgG-binding proteins. The type IIo IgG
      binding protein displayed the greatest range of reactivities, binding to all four
      human IgG subclasses, and rabbit, pig, and horse IgG. A variant of this protein,
      designated type II'o, bound all four human subclasses and rabbit IgG, but failed
      to react with pig or horse IgG. A type IIa protein was recovered from certain
      group A strains which bound human IgG1, IgG2, IgG4, as well as reacting with
      rabbit, pig, and horse IgG. A functionally related type IIc activity that
      displayed all of the reactivities of the type IIa protein but did not bind with
      human IgG2 was also identified. The final functional form of group A IgG-binding
      protein, the type IIb protein, bound exclusively to human IgG3. Comparison of
      these functionally different type II IgG-binding proteins demonstrated no simple
      structure-function relationship. These studies underscore the heterogeneity of
      type II Ig-binding proteins expressed by different group A streptococci and
      document that a single strain can change its pattern of expression of type II IgG
      binding protein both quantitatively and qualitatively.

PMID- 1991967
TI  - Neutral proteinases of human mononuclear phagocytes. Cellular differentiation
      markedly alters cell phenotype for serine proteinases, metalloproteinases, and
      tissue inhibitor of metalloproteinases.
AB  - Mononuclear phagocytes have the capacity to directly participate in extracellular
      matrix turnover via secretion of neutral proteinases. We have studied the effects
      of in vivo and in vitro differentiation upon cellular content or secretion of a
      spectrum of neutral proteinases, along with a counter-regulatory
      metalloproteinase inhibitor (TIMP). We found 1) matrix-degradative serine
      proteinases (leukocyte elastase and cathepsin G) were lost during cellular
      maturation and/or differentiation; 2) the 92-kDa type IV/type V collagenase and
      TIMP were secreted earliest in mononuclear phagocyte differentiation, whereas
      stromelysin secretion was observed only by LPS-stimulated alveolar macrophages;
      3) exposure of alveolar macrophages, but not monocytes, to phorbol esters and LPS
      resulted in markedly augmented secretion of all studied metalloproteinases and
      TIMP; 4) monocyte-derived macrophages partially (but not completely) mimicked the
      metalloproteinase secretory phenotype of alveolar macrophages; and 5) the
      secretory phenotype of alveolar macrophages for interstitial collagenase (but not
      TIMP) was largely lost during in vitro culture. These results underscore the
      complexity of the process of differentiation in human mononuclear phagocytes, and
      provide insights into the variable capacity of mononuclear phagocytes to degrade
      extracellular matrix components. Moreover, we anticipate that human mononuclear
      phagocytes at various stages of differentiation will provide a useful model
      system for study of the variable regulation of secretion of human matrix
      degrading metalloproteinases.

PMID- 1991968
TI  - Urinary nitrate excretion in relation to murine macrophage activation. Influence
      of dietary L-arginine and oral NG-monomethyl-L-arginine.
AB  - Murine macrophage oxidation of L-arginine guanidino nitrogen to nitrite/nitrate
      yields an intermediate effector, possibly nitric oxide, with antimicrobial
      activity. Total body nitrogen oxidation metabolism (NOM) was measured in vivo by
      determining the urinary nitrate excretion of mice ingesting a chemically defined
      nitrite/nitrate-free diet. As reported previously, mycobacterial infection with
      bacillus Calmette-Guerin led to a large increase in urinary nitrate excretion.
      This increase was temporally related to macrophage activation in vivo. The
      substrate for macrophage nitrogen oxidation metabolism in vitro, L-arginine, was
      deleted from the diet without ameliorating the urinary nitrate excretion response
      induced by BCG. This suggested that L-arginine was synthesized endogenously
      because there are no other known natural substrates for NOM. A competitive
      inhibitor of NOM, the L-arginine analog, NG-monomethyl-L-arginine was fed to mice
      in their drinking water. NG-monomethyl-L-arginine ingestion blocked both basal
      and bacillus Calmette-Guerin-induced urinary nitrate excretion over a 2-4 week
      time span. These experimental conditions should prove useful for further
      investigation on the role of macrophage NOM in host defense against intracellular
      microorganisms.

PMID- 1991969
TI  - Down-regulation of surface FcRI and decrease in antibody-dependent cellular
      cytotoxicity of cultured monocytes. Reversal by monensin or cytochalasin-D.
AB  - To investigate the mechanisms involved in regulation of antibody-dependent
      cellular cytotoxicity (ADCC) mediated by human monocytes, 51Cr-labeled sheep red
      blood cells (RBC) were used as target cells in vitro. Monocytes incubated
      overnight at 37 degrees C before addition of SRBC and antibody exhibited a
      significant decrease in ADCC activity compared with freshly isolated cells. This
      pattern was observed with monocytes from all donors tested, regardless of the
      media used for culture. Supernatants from monocyte cultures did not inhibit the
      cytotoxic ability of fresh monocytes and cycloheximide, a protein synthesis
      inhibitor, could not reverse ADCC suppression in cultured monocytes, indicating
      that the alteration in ADCC is probably not due to inhibitory molecules secreted
      or synthesized during incubation. A correlation between the decrease in the
      number of surface FcRI and loss in ADCC ability of cultured monocytes was found.
      One mechanism for the reduced FcRI expression of 1-day-old monocytes may be rapid
      internalization that exceeds the rate of reexpression, because cytochalasin-D or
      monensin, each of which inhibits receptor internalization, maintained FcR
      expression as well as ADCC ability of cultured monocytes. These data illustrate
      mechanisms whereby alteration in the number of receptors may underlie loss of
      receptor-mediated functions, or be involved in augmentation of their biologic
      activity. The findings that important monocyte functions change under conditions
      of storage or culture have relevance to in vitro testing of various immune
      functions of monocytes performed clinically to monitor or guide therapy.

PMID- 1991970
TI  - Binding of recombinant HIV coat protein gp120 to human monocytes.
AB  - Inasmuch as the exact level of CD4 Ag expression on macrophages is controversial
      and because HIV may interact with macrophages in a manner different from that on
      T cells, we analyzed the binding of gp120 to freshly isolated and cultured
      monocytes. rgp120 was iodinated using the lactoperoxidase method to a sp. act. of
      600 Ci/mmol. Highly purified monocytes (greater than 90%) were isolated from the
      leukapheresed blood of normal volunteers by Ficoll-Hypaque sedimentation followed
      by countercurrent centrifugal elutriation and cultured 7 days in DMEM
      supplemented with 1000 U/ml macrophage CSF in 10% human serum. Whereas MOLT/4
      cells consistently bound freshly prepared 125I-rgp120 at 80% specificity with
      5100 +/- 700 mol/cell, MCSF cultured monocytes bound rgp120 at only 0 to 20%
      specificity and 420 +/- 200 mol/cell. Most of the radioactivity bound by these
      cells could not be blocked by the addition of unlabeled rgp120. In contrast, the
      U937 myeloid cell line bound rgp120 with 50% specificity and about 2500 mol/cell.
      Whereas the antibody OKT4a (anti-CD4) blocked 80% of the binding on MOLT/4 cells
      and 50% on U937 cells, binding was only inhibited on the average of 6% on
      cultured monocytes. When soluble rCD4 was used as an inhibitor, binding to MOLT/4
      cells was blocked by 80%. In contrast, binding to cultured monocytes was
      inhibited by 28%. HIV infectivity was blocked by similar concentrations of OKT4a.
      These observations suggest that although most binding of gp120 to cultured
      monocytes is not to the CD4 determinant, several hundred molecules do bind to a
      CD4-like molecule which promotes virus entry and replication.

PMID- 1991971
TI  - Genetic control of the immune response in mice to Leishmania mexicana surface
      protease.
AB  - Congenic mouse strains were tested in the lymphocyte proliferation assay for
      their response to the purified surface protease of Leishmania mexicana (gp63).
      The data obtained allow us to distinguish three different patterns of response,
      influenced both by H-2 (class II) and non-H-2 genes. Mice of the C57BL/10 (B10)
      background carrying H-2 haplotypes b,q, and r were found to be high responders;
      those carrying H-2 haplotypes d, j, v, and z were low responders; and those with
      H-2a, H-2f, H-2k, H-2p, and H-2u haplotypes were intermediate responders. Studies
      with H-2 recombinant strains indicated that the high responsiveness on the B10
      background was determined by the Ab allele and the low responsiveness influenced
      by the Ad allele. Other genes besides H-2 appear to have a role in the immune
      response as shown by the fact that some strains with BALB, DBA, or C3H background
      differed in their pattern of responsiveness from B10 background strains carrying
      the corresponding H-2 haplotypes. By using recombinant protein, the influence of
      the leishmanial surface lipophosphoglycan that might co-purify with gp63, on the
      MHC restriction of the response to gp63 was excluded. The immune response to gp63
      did not correlate with susceptibility of mouse strains to cutaneous infection
      with L. mexicana promastigotes.

PMID- 1991972
TI  - DNA sequences 3' of the Ig H chain cluster rearrange in mouse B cell lines.
AB  - A mouse myeloma cell line MPC11 (IgG2b, kappa) and variants derived from it have
      been used to study DNA rearrangements that occur at the Ig H chain locus. One
      variant, F5.5, has acquired both VH gene and C epsilon gene rearrangements.
      Through genomic Southern blot analysis initially directed to mapping the C
      epsilon gene rearrangement, we observed that the VH region rearrangement was
      linked, through an inversion event, to sequences that originate 3' of the CH
      cluster, i.e., 3' of the C alpha gene. Subsequent studies have shown that DNA
      rearrangements within the region 3' of the C alpha gene are detected in several
      other mouse myeloma and hybridoma cell lines and are not associated with the
      expression of specific isotypes.

PMID- 1991973
TI  - The W element is a positive regulator of HLA-DRA transcription in various DR+
      cell types.
AB  - The W and P elements are cis-acting transcriptional regulators of the human class
      II MHC gene HLA-DRA necessary for maximal promoter activity in DR+ B cells.
      Proteins that bind specifically to W may mediate promoter activity from a DNA
      segment containing W and P (W/P). In this report, we demonstrate that a -143 to 
      123 bp region that lacks P is sufficient to mediate the W elements function and
      to bind the W proteins W-B1 and W-B2 in the Raji B-lymphoblastoid cell line. In
      contrast to previous reports, we find that W/P is not a B cell-specific element;
      rather that its promoter activity parallels active transcription of the
      endogenous DRA gene. In addition, we show that tissue-restricted regulation by
      W/P is not correlated with the ubiquitous (W-B1) and lymphoid-specific (W-B2)
      distribution of the W binding proteins. We suggest that mechanisms in addition to
      binding to W may account for W/P-dependent transcriptional activation in DR+
      cells.

PMID- 1991974
TI  - An autosomal recessive gene that delays expression of lupus in BXSB mice.
AB  - We report the generation and serologic, cellular, histologic, and genetic
      characteristics of a BXSB/MpJScr substrain, termed BXSB/MpJScr-ll/ll, that has
      lost early-life male lupus disease. Classic genetic analysis suggested that
      delayed disease expression results from the action of a single autosomal
      recessive gene. This putative gene, referred to as ll (long-lived), causes a
      significant delay in expression of autoimmune serology (total serum IgG and anti
      nuclear antibodies levels), monocytosis, and of immune complex-mediated
      histopathologic changes such as glomerulonephritis, arteritis, and myocardial
      infarction. Presumably as a consequence of the delayed immunopathology male
      BXSB/MpJScr-ll/ll mice live three to four times longer than regular BXSB/MpJScr.
      This strain might be useful for analysis of single genes responsible for severe
      autoimmune disease expression.

PMID- 1991975
TI  - Comparison of the effect of IL-2 and IL-6 on the lytic activity of purified human
      peripheral blood large granular lymphocytes.
AB  - The effects of IL-6 and IL-2 on highly purified, human peripheral blood large
      granular lymphocytes (LGL) were investigated and compared. IL-6 enhanced LGL NK
      activity in a dose-dependent manner against K562, however IL-2 was a more potent
      stimulus of LGL NK function. Neither IL-2 nor IL-6 increased LGL cytotoxic
      potential in a parallel estimation of heteroconjugated antibody (anti-CD16 x anti
      nitrophenyl mAb)-dependent cytotoxicity against nitrophenyl-modified YAC. Unlike
      IL-2, IL-6 did not significantly induce LGL lymphokine-activated killer activity,
      LGL proliferation, or LGL lymphokine production. In particular, IL-6 did not
      stimulate detectable LGL IL-2 production or IL-2R modulation, and mAb to the p75
      IL-2R had no effect on IL-6 induction of LGL NK activity. Therefore, in the
      absence of T cells, IL-6 provided an IL-2-independent signal to LGL that resulted
      in augmentation of their NK activity without stimulating their proliferation or
      other LGL functions.

PMID- 1991976
TI  - Regional variation in the expression of pemphigus foliaceus, pemphigus
      erythematosus, and pemphigus vulgaris antigens in human skin.
AB  - The expression of the pemphigus foliaceus (PF), pemphigus erythematosus (PE), and
      pemphigus vulgaris (PV) antigens in 16 different regions of normal human skin was
      evaluated by indirect immunofluorescence by using sera with a high titer of PF,
      PE, and PV antibodies. Regional variations were observed in the expression of all
      these antigens. The expression of the PF and PE antigens, as measured by endpoint
      titer of antibody reactivity, was highest in skin specimens obtained from the
      upper torso, and lowest in those from the buccal mucosa, lower torso, and scalp.
      This distribution pattern differed from that of PV antigen, whose expression was
      highest in buccal mucosa and scalp. These patterns correlate with, and may
      provide a partial explanation for, the different distribution of skin lesions in
      these different forms of pemphigus.

PMID- 1991977
TI  - Glycosaminoglycans production by cultured skin fibroblasts from the Pasini and
      Cockayne-Touraine forms of dominant dystrophic epidermolysis bullosa.
AB  - Qualitative and quantitative comparisons of glycosaminoglycans e (GAG) production
      were made on fibroblast lines cultured from the skin of six patients with the
      Pasini (albopapuloid) form of dominant dystrophic epidermolysis bullosa, six with
      the non-albopapuloid form (Cockayne-Touraine), eight lines from patients with
      simplex or recessive dystrophic epidermolysis bullosa and eight lines from normal
      individuals. A reasonable match of donor age and gender, site, and passage number
      was achieved. Contrary to an earlier report, the lines from the Pasini group were
      unexceptional in the amount of GAG they secreted and the proportions of sulfated
      and nonsulfated GAG showed no consistent difference from the Cockayne-Touraine or
      control lines. The Pasini lines secreted 77 +/- 18 (SEM) microgram GAG-uronic
      acid per 10(7) cells and the Cockayne-Touraine lines 81 +/- 12 micrograms at
      equivalent cells densities. Sulfated GAG represented averages of 19 +/- 4+ in
      Pasini lines, 17 +/- 5% in Cockayne-Touraine, and 14 +/- 3% in controls. These
      findings are consistent with current views of albopapuloid lesions as an
      unreliable clinical sign in epidermolysis bullosa and bring into question the
      validity of the Pasini entity.

PMID- 1991978
TI  - Transcutaneous chemical collection of caffeine in normal subjects: relationship
      to area under the plasma concentration-time curve and sweat production.
AB  - A novel transcutaneous chemical collection device (TCD) has been developed to
      study the phenomenon of outward transcutaneous chemical migration. The TCD is a
      Bandaid-like device containing an immobilized aqueous media and binding reservoir
      material to prevent back-transfer into the skin. This device, when placed against
      the skin, allows collection and quantitation of chemicals that diffuse directly
      through the skin from within the body. The relationship of the amount of drug
      collected in the TCD to the amount in the body available for collection (as
      represented by the area under the plasma-concentration time curve, AUC) and the
      effects of sweating, a potential confounding factor, on collection of drug in a
      TCD were studied, using caffeine as a model compound. TCD were placed on the skin
      of normal male volunteers. Twenty-four hours later subjects took caffeine by
      mouth. Blood samples were collected and TCD were removed at various times after
      drug intake and analyzed by HPLC for caffeine. Studies of the sweating effect
      were carried out in a similar manner, except that one arm of each subject was
      maintained at 40 degrees C to induce local sweating, the other arm acted as a non
      sweating control. The amount of caffeine collected was linearly related to the
      AUC. Sweating seemed to have a large (40%) contribution to transdermal collection
      in the early period (5.5 h) of the study, but this difference was much less (14%)
      at longer collection times (10 h).

PMID- 1991979
TI  - Examination of HTLV-I integration in the skin lesions of various types of adult T
      cell leukemia (ATL): independence of cutaneous-type ATL confirmed by Southern
      blot analysis.
AB  - The various clinical features of adult T-cell leukemia/lymphoma (ATL) are
      frequently accompanied by skin eruptions. Recently, a cutaneous type of ATL has
      been proposed by clinical studies. We analyzed the viral integration of human T
      cell leukemia virus-I (HTLV-I) and monoclonal rearrangement of T-cell receptor
      (TCR) gene in blood lymphocytes and the cutaneous infiltrated cells of nine ATL
      patients with various clinical features and skin eruptions. We classified them by
      the results of Southern blot analysis and propose a cutaneous-type ATL
      accordingly. In two of them, we could detect the monoclonal integration of HTLV-I
      and T-cell monoclonality only in the skin but not in the peripheral lymphocytes.
      We also demonstrated the time course study in one patient. Clinicians should be
      aware of the HTLV-I positive cutaneous T cell lymphoma that can be named
      cutaneous-type ATL. Examination of viral integration and T-cell monoclonality in
      skin lesions is required to make an exact diagnosis of cutaneous ATL.

PMID- 1991980
TI  - The lovastatin-treated rodent: a new model of barrier disruption and epidermal
      hyperplasia.
AB  - Recent studies have linked epidermal cholesterol synthesis with maintenance of
      the permeability barrier. To assess directly the importance of cholesterol
      synthesis, we applied lovastatin, a potent inhibitor of cholesterol synthesis, to
      hairless mouse skin. Transepidermal water loss (TEWL) began to increase after
      four to six daily applications. Co-application of cholesterol blocked the
      expected increase in TEWL, demonstrating the importance of cholesterol for
      development of the lesion. The histology of lovastatin-treated skin revealed
      epidermal hyperplasia, accompanied by accelerated DNA synthesis. Whereas
      cholesterol synthesis initially was reduced in lovastatin-treated epidermis, with
      further treatment cholesterol synthesis normalized, while fatty acid synthesis
      accelerated greatly. Although the total free sterol content of lovastatin-treated
      epidermis remained normal, the fatty acid content increased coincident with
      barrier disruption. Finally, morphologic abnormalities of both lamellar body
      structure and their deposited, intercellular contents occurred coincident with
      the emerging biochemical abnormalities. Thus, the abnormal barrier function in
      this model can be ascribed to an initial inhibition of epidermal sterol synthesis
      followed by an alteration in cholesterol and fatty acid synthesis, leading to an
      imbalance in stratum corneum lipid composition and abnormal membrane bilayer
      structure.

PMID- 1991981
TI  - Melanocytes and Langerhans cells in aged versus young skin before and after
      transplantation onto nude mice.
AB  - Previous studies have demonstrated decreased numbers of melanocytes and
      Langerhans cells (LC) in aged skin. In the present study, we employed dopa and
      indirect immunoperoxidase techniques in epidermal sheets to determine the fate of
      melanocytes and LC of aged versus young donors after skin transplantations onto
      nude mice. The detection of positive homologous leucocytic antibody reaction of
      degeneration (HLA-DR) of LC indicates an age-associated reduction in sun
      protected thigh skin in aged versus young subjects (263 +/- 63 versus 589.25 +/-
      142.643, p less than 0.001). The mean number of LC four weeks after
      transplantation remained almost constant. Prior to skin engraftment, a decreased
      number of melanocytes was found in aged versus young epidermis (160.77 +/- 51.7
      versus 255.83 +/- 81.2, respectively, p less than 0.05). A significantly
      increased number of melanocytes was noted four weeks following engraftment in
      epidermis from aged (307.44 +/- 174, p less than 0.05) and young human donors
      (402.16 +/- 139, p less than 0.02). The marked increase in density of dopa
      positive melanocytes following engraftment onto nude mice may indicate the
      existence of circulating factors in nude mice that perhaps both stimulates and
      enhances proliferation and activity of these cells.

PMID- 1991982
TI  - Membrane structures in normal and essential fatty acid-deficient stratum corneum:
      characterization by ruthenium tetroxide staining and x-ray diffraction.
AB  - Despite the importance of intercellular lamellar bilayers for stratum corneum
      (SC) barrier function, knowledge about the structure of these bilayers is limited
      due to their poor visualization and/or retention. Whereas substitution of
      ruthenium tetroxide (RuO4) for osmium tetroxide fixation provides clear images of
      these bilayers, the usefulness of RuO4 has been limited by its slow penetration
      and cytotoxicity. Utilizing a new fixation protocol for RuO4, we obtained clear
      images of lamellar domains at all levels of murine SC. Computer-aided image
      reconstructions demonstrated a lamellar spacing of 129 +/- 2 A, which agreed with
      x-ray diffraction data from parallel, unfixed samples (131 +/- 2 A), a spacing
      not affected by hydration. Furthermore, novel structures were seen in the
      intercellular spaces of normal SC. Finally, in murine essential fatty acid
      deficiency (EFAD), the overall lamellar spacing is comparable to normal [127 +/-
      7 A by computer transform vs. 131.9 +/- 2 A (hydrated) and 129.6 +/- 2.2 A (dry)
      by x-ray diffraction]. Yet, these domains are structurally abnormal, displaying
      regions with either an excess or absence of lamellae. The new RuO4 protocol
      provides quantitative information about SC lamellar dimensions and morphologic
      abnormalities in bilayer distribution and substructure in EFAD stratum corneum
      that are not detected by either x-ray diffraction or computer-aided image
      reconstruction. Thus, the barrier abnormality in EFAD stratum corneum can be
      ascribed either to focal depletion of lamellae or abnormalities in lamellar
      substructure.

PMID- 1991983
TI  - Immunolocation of TNF-alpha/cachectin in human melanoma cells: studies on co
      cultivated malignant melanoma.
AB  - We have investigated the ability of metastatic cells to produce the macrophage
      cytokine, TNF-alpha/cachectin, as these cells have macrophage-like properties
      such as infiltration and migration. We looked for TNF-alpha/cachectin in three
      tumor cell lines derived from human malignant melanomas and six co-cultivated
      malignant melanomas derived, in vitro, from these three cell lines plus angioma
      fibroblasts. Immunohistochemistry with an anti-TNF-alpha/cachectin monoclonal
      antibody showed that TNF-alpha/cachectin was produced by two of the three parent
      melanoma cell lines. All the tumor cells in both the co-cultivated malignant
      melanomas and their in vitro tumorous nodules produced TNF-alpha/cachectin, even
      those derived from the melanoma cell line, which originally did not. The results
      clearly show that TNF-alpha/cachectin can be produced by non-hematopoietic tumor
      cells. A co-cultivated tumor model prepared from other types of human tumor cell
      lines promises to provide a useful tool for exploring the relationship between
      TNF-alpha/cachectin and oncogenesis.

PMID- 1991984
TI  - Comparative effects of interleukin-1 and tumor necrosis factor-alpha on collagen
      production and corresponding procollagen mRNA levels in human dermal fibroblasts.
AB  - The effects of recombinant human Interleukin-1 alpha (IL-1 alpha), Interleukin-1
      beta (IL-1 beta), and Tumor Necrosis Factor-alpha (TNF-alpha) on collagen
      biosynthesis were studied in vitro using dermal fibroblast cultures. Both forms
      of IL-1 and TNF-alpha induced a dose-dependent inhibition of both types I and III
      collagen synthesis, as measured by radioimmunoassay, gel electrophoresis, or
      collagenase-sensitive material. This effect was accompanied by a significant
      release of prostaglandin E2 into the culture medium. However, indomethacin, a
      potent inhibitor of prostaglandin synthesis, could not prevent the inhibitory
      effect of the three cytokines on collagen synthesis. Measurement of type I and
      type III procollagen mRNA levels in IL-1 treated cells revealed that both IL-1
      alpha and IL-1 beta were potent enhancers of procollagen gene expression at
      pretranslational level. On the other hand, TNF-alpha was found to reduce the
      steady-state levels of type I and III procollagen mRNA in a dose-dependent
      manner. Quantitation of IL-1 beta and TNF-alpha transcripts following TNF-alpha
      treatment of fibroblasts indicated that this cytokine can induce IL-1 beta gene
      expression in these cells. By contrast, TNF-alpha mRNA remained at a constant
      level after TNF-alpha exposure. These data suggest that IL-1 and TNF-alpha, two
      cytokines that share several biologic activities, modulate collagen deposition in
      dermal fibroblasts by mechanisms that are clearly different: TNF-alpha appears to
      act at a transcriptional level to inhibit collagen synthesis, whereas IL-1
      inhibitory action involves important translational regulation, still unknown,
      that counterbalances its stimulatory effect on procollagen mRNA levels. Moreover,
      our data suggest the existence of local fibroblastic cytokine production that may
      be involved in the modulation of extracellular matrix deposition.

PMID- 1991985
TI  - Immunohistochemical alterations in basement membrane components of squamous cell
      carcinoma.
AB  - To investigate alterations in the basement membrane (BM) in squamous cell
      carcinoma (SCC), we investigated 20 tumors. Four had the cytologic
      characteristics of Bowen's disease (SCC-BD) and 16 did not have them (SCC-NB).
      Tumors were studied immunohistochemically by double immunofluorescent staining by
      using mouse monoclonal antibodies to the core protein of heparan sulfate
      proteoglycan (HSPG) and chondroitin 6-sulfate glycosaminoglycan (Ch6S) as well as
      rabbit antiserum to laminin (LN) and type IV collagen (C-4). In well
      differentiated and highly keratinized SCC-NB, LN, C-4, and HSPG could be detected
      in the tumor nest BM and showed no loss of continuity, but they were largely lost
      in poorly differentiated and poorly keratinized SCC-NB. This suggests that poorly
      differentiated SCC-NB cause greater enzymatic degradation of BM components than
      well-differentiated SCC-NB. Ch6S was detected in parts of the BM of SCC-BD, but
      it was absent in all SCC-NB examined. It appears that SCC-NB have lost the
      ability to synthesize Ch6S, and that SCC-BD degrade Ch6S although they continue
      to produce it. Thus, it appears that in SCC the BM is qualitatively different
      from that of normal epidermis, and that SCC-BD can be distinguished from SCC-NB
      by the Ch6S content of the BM.

PMID- 1991986
TI  - Effects of in vitro UVA irradiation and PUVA treatment on membrane fatty acids
      and activities of antioxidant enzymes in human keratinocytes.
AB  - Human Keratinocytes (NCTC 2544) in culture were exposed to either plain
      ultraviolet A (UVA) irradiation or to 8-methoxypsoralen plus UVA (PUVA)
      treatment. Lipid peroxidation, activities of antioxidant enzymes, and percentage
      amounts of 14C-arachidonic acid in various cellular lipid subclasses and in the
      culture medium were measured. Both UVA irradiation and PUVA treatment induced
      significant changes in the distribution of arachidonic acid and increased the
      liberation of arachidonic acid from membrane phospholipids. At 24 h after either
      UVA irradiation or PUVA treatment the formation of thiobarbituric acid reactive
      material was significantly increased, whereas the amount of conjugated dienes was
      unaffected. The activities of the antioxidant enzymes, catalase and superoxide
      dismutase, were already significantly decreased at 0.5 h after UVA irradiation or
      PUVA treatment. The enzyme activities were partially restored during the
      following 24 h incubation. From the present study, we suggest that in
      keratinocytes both plain UVA irradiation and PUVA treatment induce changes in the
      distribution of membrane fatty acids and cause an impairment in the enzymic
      defense system against oxidative stress.

PMID- 1991987
TI  - Secretion of a unique collagen by spontaneously transformed murine keratinocytes
      (PAM cells) in vitro.
AB  - A spontaneously transformed murine keratinocyte cell line (PAM cell) was found to
      secrete two nondisulfide-linked collagenous polypeptides with apparent molecular
      weight (MW) 190-kd and 120-kd. Pulse-chase experiments indicated that the 190-kd
      polypeptide was secreted into the culture medium in 2 h and processed to the 120
      kd collagen component within 4 h. This process was inhibited by EDTA. The 120-kd
      polypeptide was sensitive to pepsin, and a 50-kd fragment was produced by a mild
      pepsin treatment at 4 degrees C. A cyanogen bromide peptide map of the 120-kd
      polypeptide was distinct from that of types I, II, III, IV, and V collagens.
      These properties indicate similarities to the type VIII-related collagen produced
      by human astrocytoma cells. The secretion of the collagen rapidly reached a
      maximum level on the first day of culture and subsequently declined with cell
      proliferation. An accelerated processing to the 120-kd polypeptide was observed
      under culture conditions of high cell density. Similar collagens were also found
      to be produced by normal human keratinocytes. These results indicate that the 120
      kd polypeptide is a potentially functional protein that may participate in the
      formation of the extracellular matrix of keratinocytes.

PMID- 1991988
TI  - Drug-induced pemphigus: autoantibodies directed against the pemphigus antigen
      complexes are present in penicillamine and captopril-induced pemphigus.
AB  - Pemphigus is an autoimmune blistering disease characterized by circulating
      autoantibodies directed against the keratinocyte cell surface. The two variants,
      pemphigus foliaceus and pemphigus vulgaris, can be distinguished at the molecular
      level by immunochemical studies. The large majority of patients with pemphigus
      develop the disease spontaneously; however, there is a small group of patients
      who develop pemphigus after treatment with certain medications, of which
      penicillamine and captopril are the best documented. Most patients with drug
      induced pemphigus have circulating and/or tissue bound epidermal cell surface
      autoantibodies; however, the molecular specificity of these autoantibodies has
      not been studied. We performed immunoprecipitation studies utilizing extracts of
      125I-labeled suction blister epidermis and the sera of three patients with drug
      induced pemphigus foliaceus (two due to penicillamine and one due to captopril)
      and one patient with captopril-induced pemphigus vulgaris. We found that the
      three patients with drug-induced pemphigus foliaceus had circulating
      autoantibodies that are directed against the pemphigus foliaceus antigen complex
      and that the one patient with drug-induced pemphigus vulgaris had circulating
      autoantibodies that are directed against the pemphigus vulgaris antigen complex.
      This study demonstrates that autoantibodies from drug-induced pemphigus patients
      have the same antigenic specificity, on a molecular level, as do autoantibodies
      from other pemphigus patients.

PMID- 1991989
TI  - Immunohistochemical localization of parathyroid hormone-related protein (PTHRP)
      in normal human skin.
AB  - Human keratinocytes secrete large amounts of a parathyroid hormone-related
      peptide (PTHRP) in vitro. Because recent studies indicate that PTHRP could have a
      number of autocrine or paracrine functions in the skin, localization of this
      peptide in vivo is important. A monoclonal and two affinity-purified polyclonal
      antibodies were employed to locate PTHRP in normal human skin and cultivated
      human keratinocytes. PTHRP is present throughout the viable portion of the
      epidermis, in adnexal epithelial cells, and in all cultivated keratinocytes.
      These findings do not support the provocative suggestion that PTHRP is a marker
      for squamous differentiation.

PMID- 1991990
TI  - Identification of a melanoma progression antigen as integrin VLA-2.
AB  - The expression of the integrin receptors VLA-1, -2, -3, and -6 was studied in
      normal cultured melanocytes and in five melanoma cell lines. Normal melanocytes
      synthesized VLA-3, but did not reveal detectable levels of VLA-1, -2, and -6. All
      melanoma cell lines, however, expressed VLA-2, -3, and -6. VLA-1 was synthesized
      by two of five melanoma lines. In parallel, we had analyzed the expression of
      four previously characterized melanoma cell surface antigens. One of them
      (antigen A.1.43), which is associated with tumor progression of human melanoma,
      revealed a striking similarity to VLA-2. In sequential immunoprecipitation
      experiments, we show that A.1.43 is identical with the integrin VLA-2, a cell
      surface receptor for collagen, laminin, and fibronectin.

PMID- 1991991
TI  - Effects of butylated hydroxyanisole on ornithine decarboxylase activity and its
      gene expression induced by phorbol ester tumor promoter.
AB  - Butylated hydroxyanisole (BHA) is a phenolic antioxidant that has been found to
      suppress the activity of skin tumor promoters. In this study, we investigated the
      effect of BHA on the activity of ornithine decarboxylase (ODC, an indicator of
      tumor promotion) and its gene expression induced by 12-O-tetradecanoyl-phorbol-13
      acetate (TPA) in mouse skin. TPA-induced ODC activity was markedly inhibited by
      the topical application of 55 mumol of BHA (the inhibition rate at 6 h was about
      80%). In Northern and dot-blot analysis, the TPA-induced increase in ODC mRNA was
      shown to be markedly reduced by the same dose of BHA (the inhibition rate at 4 h
      was about 60%). These results suggest the involvement of a decrease in ODC gene
      expression in the mechanism of the inhibition of ODC activity by BHA.

PMID- 1991992
TI  - The award of the Fothergillian Gold Medal to Robert Willan in 1790 (a
      bicentennial not to be forgotten)

PMID- 1991993
TI  - 8-Methoxypsoralen acts on lymphocyte membranes in the dark.

PMID- 1991994
TI  - Interleukin-1 alpha in normal skin.

PMID- 1991995
TI  - Distribution of neutral endopeptidase activity in human blood leukocytes.
AB  - We investigated the distribution of neutral endopeptidase (NEP; EC 3.4.24.11)
      activity, a possible regulatory enzyme for neuropeptide-induced leukocyte
      activations, in each cell type of human blood leukocytes. The NEP activity
      assessed by an NEP inhibitor phosphoramidon-sensitive Met5-enkephalin degrading
      activity was present in neutrophils and the common acute lymphoblastic leukemia
      antigen (CALLA)-positive leukemic cells (59 pmol/min/10(6) cells and 62
      pmol/min/10(6) cells, respectively); however, the NEP activity was virtually
      absent in lymphocytes, monocytes, eosinophils, basophils, CALLA-negative leukemic
      cells, or a promyelocytic cell line HL-60. The enzymatic activity was
      characterized as NEP on the basis of the values of kinetic parameters (Km = 61
      microM, Kcat = 1,692 min-1, and Kcat/Km = 28 min-1 microM-1) and the values of
      IC50 of two NEP inhibitors phosphoramidon and thiorphan (7.4 nM and 8.4 nM,
      respectively). The distribution of NEP detected immunocytochemically using anti
      NEP monoclonal antibodies was also found to be parallel with the distribution of
      NEP activity among peripheral blood leukocytes.

PMID- 1991996
TI  - Splenic macrophages from tumor-bearing mice co-expressing MAC-1 and MAC-2
      antigens exert immunoregulatory functions via two distinct mechanisms.
AB  - Tumor burden has been shown to induce a variety of phenotypic and functional
      changes in the cellular constituents of the host's immune system. These changes
      have been implicated as mechanisms by which tumors avoid rejection. Studies of
      BALB/c mice bearing a D1-DMBA-3 mammary adenocarcinoma showed alterations of the
      splenocyte populations. There was a five-fold increase of macrophages (M phi)
      that were phenotypically and functionally analyzed to establish their role in
      tumor-induced modifications of the host's immune response. Monoclonal antibody
      staining defined a Mac-1+2+ population which comprised up to 20% of the
      splenocytes in tumor-bearers (TB), but is negligible in spleens from normal mice.
      These Mac-1+2+ M phi were found to mediate down-regulation of both polyclonal and
      antigen-specific T and B cell responses in vitro and in vivo. Although B cell
      responses were suppressed via prostaglandin E2 (PGE2) production by the TB M phi,
      T cell responses were relatively refractory to PGE2-mediated down-regulation.
      Instead, they were suppressed by a contact-dependent T cell-M phi interaction.
      Furthermore, tumor-derived factors such as granulocyte-M phi colony-stimulating
      factor (GM-CSF) seem to play an important role in the induction and expansion of
      the Mac-1+2+ M phi. These cells appear to mediate down-regulation of the host
      immune responses by at least two distinct mechanisms: 1) PGE2 production and 2) a
      cell contact-dependent, but non-major-histocompatibility-complex-specific,
      interaction.

PMID- 1991997
TI  - Effects of interleukin 4 upon human tumoricidal cells obtained from patients
      bearing solid tumors.
AB  - The use of human interleukin 4 (IL4) in the generation of tumoricidal effector
      cells derived from cancer patients undergoing either interleukin 2/lymphokine
      activated killer cells (IL2/LAK) therapy or tumor derived activated cell (TDAC)
      therapy was examined in the present study. Human IL4 alone did not generate LAK
      cells from patients undergoing IL2/LAK therapy when cultured in media containing
      2% AB serum (five out of six patients). However, when the serum free medium, Aim
      V, was used, IL4 did generate LAK cells (eight out of nine patients), although
      not as cytotoxic as those activated with IL2. When cells were cultured in both
      IL2 and IL4 during the generation of LAK cells (3-7 days), better cell recoveries
      were frequently observed. The cytolytic activity of these cells against Daudi
      target cells was slightly reduced when compared to that response induced by IL2.
      This inhibition of LAK activity by IL4 was dose dependent with 1,000 U/ml IL4
      producing maximal effects. This form of inhibition did not correlate with any
      phenotypic differences between those cells cultured in IL2 and those cells
      cultured in IL2 plus IL4. The IL4 mediated inhibition was also observed when the
      cells were cultured in Aim V medium which contains indomethacin. This inhibition
      induced by IL4 could not be overcome by using supra-optimal IL2. In addition to
      its effect during the generation of IL2 induced LAK cells, IL4 also appeared to
      reduce the cytolytic activity of pre-activated mature LAK cells. These results
      suggest that IL4 has a complex role in regulating the actions of LAK cells
      induced by lymphokines. When IL4 was used with IL2 during the first 5 weeks of
      growth of TDAC, an enhanced growth was observed when compared to the growth of
      TDAC when only one lymphokine was used. Besides the growth enhancement of TDAC, a
      better cytolytic response was observed when both lymphokines were used together.
      Thus, for the best growth of TDAC both IL2 and IL4 are required.

PMID- 1991998
TI  - Inhibition of cluster formation and lymphocyte proliferation by anti-fibronectin
      antiserum.
AB  - Dendritic cells (DC) confer concanavalin A responsiveness to accessory cell
      depleted canine lymphocytes. DC-lymphocyte cluster formation is followed by blast
      transformation and proliferation of lymphocytes. We investigated whether
      fibronectin, which is known to be involved in cell:cell interactions, might also
      be involved in the interaction between canine DC and lymphocytes. The addition of
      rabbit anti-dog fibronectin antiserum to concanavalin A-stimulated peripheral
      blood mononuclear cells decreased cluster formation and reduced 3H-thymidine
      incorporation by 57-70%. Similarly, when cell fractions, enriched for DC, were
      pretreated with anti-fibronectin antiserum before being added back to accessory
      cell-depleted lymphocytes, cluster formation was reduced and lymphocyte
      proliferation after concanavalin A stimulation decreased by 18-46% as measured by
      3H-thymidine uptake. Ferritin-conjugated anti-fibronectin antibody was bound to
      the surface of DC, primarily at the dendritic processes. We conclude that
      fibronectin, located on the surface of canine DC, participates in the accessory
      cell function of these cells.

PMID- 1991999
TI  - Gelatin sponge model of effector recruitment: tumoricidal activity of adherent
      and non-adherent lymphokine-activated killer cells after culture in interleukin
      2.
AB  - This study examined the specific tumoricidal activity of lymphokine-activated
      killer (LAK) cells derived from tumor-infiltrating lymphocytes that prevent the
      growth of secondary tumors in animals harboring progressing primary tumors. A pre
      implanted gelatin sponge was employed to capture infiltrating host effectors
      during the expression of concomitant tumor immunity. Additionally, this study
      compared the cytolytic activity of these sponge-derived cells with those of
      counterpart splenic lymphocytes. The cells from both sources were cultured for 4
      days in IL-2 to generate LAK cells which were further expanded in IL-2-containing
      medium for up to 11 days. The cytotoxic activities of these cells were measured
      in a Chromium-51 release assay. The data revealed that the culture of splenic, or
      sponge-derived lymphocytes results in the emergence of non-adherent and adherent
      cell populations with LAK activity. The 4-day sponge-derived LAK cells (adherent
      and non-adherent) exhibited significant cytolysis of EMT6 cells while the spleen
      derived counterparts showed minimal cytotoxicity toward these targets. Some NK
      activity in LAK cells derived from both sources was evident by their lysis of YAC
      1 cells. LAK cells from both sources were incapable of lysing histo-compatible EL
      4 (H-2b) tumor cells. The lysis of the EMT6 cells by the sponge-derived LAK cells
      was maintained over an 11-day period of culture in IL-2. Conversely, the spleen
      derived LAK cells were unable to significantly lyse EMT6 cells during this period
      of in vitro culture. These results show the superior specific tumoricidal
      activity of LAK cells derived from lymphocytes mediating tumor rejection in vivo
      (sponge-derived) over that of counterpart splenic lymphocytes.

PMID- 1992001
TI  - The deficient migration in vitro of lung macrophages from newborn rats normalizes
      after three days of maturation in situ.
AB  - Because there are functional deficiencies in neonatal phagocytes, we investigated
      age-dependent differences in the directed migration of rat pulmonary macrophages
      (PM). Directed migration of PMs from newborn (less than 24 h old) rats towards
      partially purified rat C5a was lower than that of PMs from adults, but reached
      adult levels by the third post-natal day. Calculation of the dose of C5a
      resulting in a half-maximal migratory response (ED-50) revealed that the ED-50s
      for all age groups studied were similar. These results suggest that responding
      PMs at all times after birth have comparable sensitivity to C5a, but that a lower
      percentage of newborn PMs migrate toward this factor because of defects in either
      signal transduction or cell motility.

PMID- 1992000
TI  - Granule changes of human skin mast cells characteristic of piecemeal
      degranulation and associated with recovery during wound healing in situ.
AB  - Human skin mast cells (HSMC) in situ were examined by electron microscopy of
      surgical biopsy specimens obtained from a wide variety of circumstances. From
      these studies, it is apparent that the general ultrastructural morphology of
      normal HSMC is similar to that of human mast cells from other sites, except that
      the most prevalent granule pattern is that of crystal granules. Scroll granules,
      particle granules, and mixed granules can also occur in HSMC. Cytoplasmic lipid
      bodies occur in HSMC extremely rarely, unlike mast cells from lung and gut.
      Circumstances in which piecemeal degranulation (PMD) of HSMC occurs, such as
      bullous pemphigoid, examined at high magnifications, revealed typical, focal
      geographic losses from cytoplasmic granules, often leaving completely empty
      granule containers in the cytoplasm. Crystal portions of mixed granules were
      uniquely susceptible to granule losses typified by PMD. Cytoplasmic smooth
      vesicles were prominent in PMD. These structures were either empty or contained
      granule-like dense materials and were free in the cytoplasm or attached to
      granules. HSMC present in wound healing revealed recovery from PMD losses.
      Typically these granules contained numerous irregular foci of markedly dense new
      granule products within empty or partially empty granule containers. The
      morphology of PMD and recovery of HSMC in vivo is contrasted with the morphology
      of anaphylactic degranulation (AND) and recovery of human mast cells ex vivo.

PMID- 1992002
TI  - Developmental neurobiology of the zebrafish.

PMID- 1992003
TI  - NGF gene expression in actively growing brain glia.
AB  - Previous work suggested that brain NGF acts locally on cells adjacent to sites of
      synthesis, in addition to any putative actions on distant, projecting perikarya.
      To define the basis of local action, we used a sensitive nuclease protection
      assay to identify cells expressing the NGF gene in vivo and in vitro. In addition
      to neurons, glia from a variety of developing brain areas synthesized NGF mRNA,
      suggesting that CNS glia exhibit a generalized capacity to express the gene.
      Expression was associated with active glial growth. Stimulation of growth with
      serum increased NGF message 2-fold in culture. Moreover, rapidly growing, low
      density glial cultures exhibited 8-fold higher levels of NGF mRNA than quiescent,
      confluent cultures. The optic nerve, which contains all 3 major types of glia,
      expressed the message in vivo during neonatal development. In contrast,
      expression was barely detectable in the adult optic nerve. Transection, which
      induces glial proliferation, elicited de novo appearance of NGF mRNA in the adult
      nerve. Our observations suggest that active glial growth is associated with
      expression of the NGF gene and raise the possibility that actively growing glia
      in the developing or injured brain regulate neuronal growth through the
      elaboration of NGF.

PMID- 1992004
TI  - Intracellular Ca2+ suppressed a transient potassium current in hippocampal
      neurons.
AB  - The effects of intracellular Ca2+ (Ca2+i) on K+ currents in hippocampal cells
      were examined using acutely isolated cells obtained from adult guinea pigs. Whole
      cell voltage-clamp recordings were carried out in a configuration that allowed a
      continuous perfusion of the intracellular medium. Recording media were made to
      block inward currents and allowed selective activation of K(+)-dependent outward
      currents. Voltage-dependent outward currents consisted of an initial rapidly
      decaying component followed by a sustained component. The time constant of decay
      of the transient current was about 25 msec, and previous studies (Numann et al.,
      1987) showed that the kinetic and pharmacological properties of this current
      closely resembled the A current recorded in invertebrate neurons (Connor and
      Stevens, 1971; Thompson, 1982). Intracellular perfusion of hippocampal cells with
      a solution containing elevated Ca2+ (about 4.5 x 10(-4) M) elicited outward
      currents at the holding potential (-45 to -55 mV) and produced changes in voltage
      dependent K+ currents. The transient outward current (IA) activated by
      depolarization was suppressed with increases in Ca2+i. Delayed, sustained K+
      currents were greatly potentiated. Data also showed that, among the 3 effects
      elicited by Ca2+i, suppression of IA was most sensitive to Ca2+i elevation.
      Previous results (Numann et al., 1987) showed that IA had a lower threshold
      (about -45 mV) than sustained currents (about -40 mV). By using low levels of
      depolarization (-40 mV), IA can be selectively activated, and the suppressive
      effect of Ca2+i on IA was confirmed on the kinetically isolated IA.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1992005
TI  - Temporal interactions in the cat visual system. I. Orientation-selective
      suppression in the visual cortex.
AB  - The perception of a visual contour depends on the spatial and temporal context in
      which it is viewed. Interactions between visual contours are believed to underlie
      a wide range of perceptual phenomena, including geometric illusions and
      aftereffects, contrast adaptation, and visual masking. The physiological
      mechanisms that might underlie such interactions were studied in the visual
      cortex of the cat by recording responses of single neurons to pairs of brief
      stationary stimuli that were separated in time. The results revealed a long
      lasting, orientation-selective suppression, termed "paired-pulse suppression,"
      which was strongest at the cell's preferred orientation, but which was more
      broadly tuned for orientation than the excitatory response of the cell. Although
      the strength and duration of the suppression varied widely, some degree of
      response reduction was present in most cells studied. The function of this
      suppression may be to regulate the gain with which visual inputs are transmitted
      to cortical neurons, thus preventing response saturation and positive feedback.

PMID- 1992006
TI  - Temporal interactions in the cat visual system. II. Suppressive and facilitatory
      effects in the lateral geniculate nucleus.
AB  - Extracellular responses were recorded from single neurons in the lateral
      geniculate nucleus (LGN) of the cat during presentation of pairs of brief visual
      stimuli identical to those that produce orientation-selective paired-pulsed
      suppression in the visual cortex. LGN neurons also show paired-pulse suppression,
      but the suppression is not orientation selective, and it occurs only for short
      interstimulus intervals (ISIs; usually less than 200 msec). At longer ISIs, most
      LGN neurons show a period of facilitation. Thus, the paired-pulse suppression in
      the LGN cannot account for that seen in the visual cortex. Paired-pulse
      suppression in the LGN was found to be enhanced by stimulation of the receptive
      field surround. LGN neurons also showed a second type of suppression, termed
      "offset suppression," which consisted of a more long-lasting suppression of
      spontaneous activity following the offset of an excitatory visual stimulus. The
      suppression of spontaneous activity was accompanied by a reduction of the
      antidromic excitability, assessed by stimulating LGN axons within the cortex or
      optic radiation. Unlike paired-pulsed suppression, offset suppression was not
      enhanced by increased stimulation of the receptive field surround. Paired-pulse
      suppression and offset suppression are most likely due to different mechanisms
      because they have different time courses and depend differently on the spatial
      properties of the stimuli. Functionally, paired-pulse suppression may be related
      to the reduced visual sensitivity that accompanies eye movements, while offset
      suppression may serve to enhance temporal contrast.

PMID- 1992007
TI  - Temporal interactions in the cat visual system. III. Pharmacological studies of
      cortical suppression suggest a presynaptic mechanism.
AB  - When tested with pairs of brief visual stimuli, neurons of the primary visual
      cortex of the cat show a long-lasting, orientation-selective suppression, termed
      "paired-pulse suppression." The hypothesis that this suppression is due to GABAA
      mediated inhibition was tested by performing temporal interaction tests before,
      during, and after iontophoretic application of the selective antagonist
      bicuculline methiodide (BMI). In keeping with previous reports, BMI elevated the
      spontaneous and evoked firing rates of cortical neurons, and altered basic
      receptive field properties. Under the influence of BMI, most neurons showed a
      reduced or abolished selectivity for stimulus orientation and direction of
      movement. The effects on orientation selectivity required higher ejection
      currents than did the effects on directional selectivity. At high ejection
      currents, most cells did lose selectivity for the orientation of a moving
      stimulus, but retained some selectivity for the orientation of a stationary
      stimulus. BMI, even at very high ejection currents, did not abolish paired-pulse
      suppression. In some cells, BMI enhanced or prolonged paired-pulse suppression.
      In further experiments, temporal interaction tests were performed in which one or
      the other of the component stimuli was replaced with a pharmacological stimulus
      (a pulse of glutamate or potassium). A pharmacological stimulus did not produce
      suppression of the response to a subsequent visual stimulus, nor did a visual
      stimulus suppress the response to a subsequent pharmacological stimulus. Paired
      pulse suppression occurred only when both stimuli were visual. Taken together
      with previous results, the present data indicate that paired-pulse suppression is
      most likely due to a presynaptic mechanism.

PMID- 1992008
TI  - Hypertension induced by hypothalamic transplantation from genetically
      hypertensive to normotensive rats.
AB  - The role of the hypothalamus (HTH) in the pathogenesis of genetic hypertension
      was studied in spontaneously hypertensive rats (SHR). It is currently believed
      that, in this strain, the genetic defect manifests itself mainly in the HTH. We
      examined this hypothesis by grafting HTH neurons from embryos of SHR or control
      Wistar Kyoto (WKY) rats into the HTH of adult normotensive WKY rats. Changes in
      host systolic blood pressure (SBP) were monitored, and alterations in vasoactive
      intestinal polypeptide (VIP) gene expression of the host brain were studied. In
      rats grafted with HTH tissue from SHR embryos (G-SHR), the blood pressure rose by
      31% as compared with that in the grafted control group. The blood pressure
      climbed gradually over a period of 6 weeks to its highest level, which was
      maintained for at least 3 months following grafting. Along with the elevated
      blood pressure, the heart weight increased by 80% compared to controls.
      Behavioral changes were also evident in the G-SHR rats, and these were similar to
      those of the native SHR strain. In situ hybridization histochemistry showed a 40%
      elevation in VIP transcripts in the suprachiasmatic nucleus of the host G-SHR
      brain compared to controls. These studies demonstrate that transplantation of
      embryonic SHR HTH tissue into brains of adult normotensive rats results in the
      development of hypertensive characteristics in the host. It thus appears that the
      HTH is a prime candidate for the source of changes leading to spontaneous
      hypertension in mammals.

PMID- 1992009
TI  - Acidic and basic fibroblast growth factors in the nervous system: distribution
      and differential alteration of levels after injury of central versus peripheral
      nerve.
AB  - Acidic and basic fibroblast growth factors (aFGF and bFGF) are known to stimulate
      mitogenesis in a variety of non-neuronal cell types. Recent work has also
      established that FGFs can act as neurotrophic factors that promote the survival
      and regeneration in vitro of a variety of neurons. The present study investigates
      the distribution of aFGF and bFGF in vivo by using a mitogenic bioassay on AKR-2B
      cells coupled with Western-blot analysis to estimate the levels of aFGF and bFGF
      in different areas of the rat nervous system. Acidic FGF and bFGF from extracts
      of nervous tissue were found to differ considerably in their relative
      dependencies upon heparin to potentiate their mitogenic activities: the effect of
      aFGF was strongly dependent upon heparin, whereas the effect of bFGF was only
      slightly potentiated by heparin. Heparin was also found to stimulate
      differentially the mitogenic activity of extracts prepared from different areas
      of the nervous system, indicating that spinal cord, cortex, pituitary, and optic
      nerve contained different ratios of aFGF to bFGF, whereas sciatic nerve contained
      extremely high levels of only aFGF. These results were confirmed in Western-blot
      experiments, using antibodies specific for either aFGF or bFGF. Transection of
      nerves had opposing effects in sciatic and optic nerves: aFGF rapidly declined in
      the sciatic nerve distal to the cut, whereas bFGF increased slightly in the
      distal portion of the cut optic nerve. This differential effect of injury on FGF
      levels in central versus peripheral nerves may reflect the differential
      regenerative potential of these two types of nerves.

PMID- 1992010
TI  - Factors that determine the magnitude and time course of human H-reflexes in
      locomotion.
AB  - The soleus H-reflex amplitude is deeply modulated during locomotion in humans
      (Capaday and Stein, 1986). Moreover, at a constant stimulus intensity, the slope
      of the relationship between the amplitude of the soleus H-reflex and the
      background electromyogram (EMG) changes with different locomotor tasks (Capaday
      and Stein, 1987a). Two further aspects are studied here. First, we recorded the
      reflex during overlapping speeds of walking (2.0-7.5 km/hr) and running (5-9
      km/hr) to determine whether the speed, the motor output, or the form of
      locomotion was most important in setting the slope of this relationship between H
      reflex and background EMG. Second, we determined the time course of change in the
      H-reflex amplitude and the possible site of action for the reflex depression
      during the transition from standing to walking. The primary determinant of the
      slope was found to be the form of locomotion. The differences between running and
      walking could not be explained entirely by either movement speed or motor output.
      For walking, the slope varied inversely with the speed and the motor output of
      locomotion. This compensation in slope as a function of motor output may prevent
      saturation of the motoneuron pool. The appropriate reflex amplitudes for a
      particular locomotor pattern are activated rapidly and completely within a
      reaction time, and simultaneously with the activation of muscle activity for the
      initiation of walking. Mechanisms for the rapid change seen during the initiation
      of locomotion most likely act presynaptically on the muscle spindle afferents.
      The time course and magnitude of this change are correlated with the activity of
      the tibialis anterior muscle.

PMID- 1992011
TI  - Voltage-gated currents in identified rat olfactory receptor neurons.
AB  - Whole-cell recording techniques were used to characterize voltage-gated membrane
      currents in neonatal rat olfactory receptor neurons (ORNs) in cell culture.
      Mature ORNs were identified in culture by their characteristic bipolar
      morphology, by retrograde labeling techniques, and by olfactory marker protein
      (OMP) immunoreactivity. ORNs did not have spontaneous activity, but fired action
      potentials to depolarizing current pulses. Action potentials were blocked by
      tetrodotoxin (TTX), which contrasts with the TTX-resistant action potentials in
      salamander olfactory receptor cells (e.g., Firestein and Werblin, 1987).
      Prolonged, suprathreshold current pulses evoked only a single action potential;
      however, repetitive firing up to 35 Hz could be elicited by a series of brief
      depolarizing pulses. Under voltage clamp, the TTX-sensitive sodium current had
      activation and inactivation properties similar to other excitable cells. In TTX
      and 20 mM barium, sustained inward current were evoked by voltage steps positive
      to -30 mV. This current was blocked by Cd (100 microM) and by nifedipine (IC50 =
      368 nM) consistent with L-type calcium channels in other neurons. No T-type
      calcium current was observed. Voltage steps positive to -20 mV also evoked an
      outward current that did not inactivate during 100-msec depolarizations. Tail
      current analysis of this current was consistent with a selective potassium
      conductance. The outward current was blocked by external tetraethylammonium but
      was unaffected by Cd or 4-aminopyridine (4-AP) or by removal of external calcium.
      A transient outward current was not observed. The 3 voltage-dependent
      conductances in cultured rat ORNs appear to be sufficient for 2 essential
      functions: action potential generation and transmitter release. As a single
      odorant-activated channel can trigger an action potential (e.g., Lynch and Barry,
      1989), the repetitive firing seen with brief depolarizing pulses suggests that
      ORNs do not integrate sensory input, but rather act as high-fidelity relays such
      that each opening of an odorant-activated channel reaches the olfactory bulb
      glomeruli as an action potential.

PMID- 1992012
TI  - Residual motion perception in a "motion-blind" patient, assessed with limited
      lifetime random dot stimuli.
AB  - A neurological patient (L.M.) suffering a specific loss of visual motion
      perception (Zihl et al., 1983) due to extrastriate cortical damage was studied
      using random dot "limited-lifetime" stimuli with a direction discrimination task.
      With a stimulus like that of Newsome and Pare (1988), the patient exhibited a
      severe deficit for motion perception, only being able to perform well for very
      high values of coherence. Different versions of the stimulus were employed to
      separate out the effects of limited lifetime versus the effects of additive noise
      as coherence was lowered. When all "signal" dots had a fixed, specified value of
      lifetime, and varying percentages of "noise" dots were added, the patient showed
      a profound deficit. In contrast, a stimulus consisting of no noise dots at all,
      and signal dots having fixed values of lifetime, revealed relatively good
      performance for surprisingly brief dot lifetimes. Thus, it is the presence of
      noisy, incoherent dot motion, rather than brief lifetimes, that causes such poor
      performance on the stimulus of Newsome and Pare (1988). Most surprising was the
      finding that the presence of even very small percentages of stationary noise dots
      was sufficient to disrupt totally direction discrimination of moving signal dots.
      The findings reported here suggest that one major role of extrastriate cortical
      processing might be the interpretation of stimuli that suffer from an impaired
      signal-to-noise ratio; the most commonly encountered form of "noise" would
      presumably be contamination by irrelevant directional spatio-temporal frequency
      components.

PMID- 1992013
TI  - Stages of growth of hamster retinofugal axons: implications for developing axonal
      pathways with multiple targets.
AB  - Neurons in many regions of the CNS (e.g., cortical areas, thalamic nuclei) are
      heterogeneous with regard to their afferent and efferent connections. Using the
      hamster retinofugal system as a model, we investigated the mechanisms by which
      such connectional heterogeneity arises during ontogeny. Retinal ganglion cell
      axons were labeled with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine
      perchlorate (Dil) in paraformaldehyde-fixed tissue. The fluorescent label was
      photoconverted to a diaminobenzidine reaction product. The morphology of the
      axons, including their trajectories, branching patterns, and growth cones, was
      studied at the level of the dorsal lateral geniculate nucleus (LGd) from
      embryonic day 14 to adulthood. In adult hamsters, axons of retinal ganglion cells
      (RGCs) are spatially segregated at the level of the lateral geniculate nucleus
      into a superficial optic tract, situated just beneath the pia, and an internal
      optic tract consisting of fascicles running parallel to the pia within the
      geniculate. All retinofugal axons project to the midbrain, but only superficial
      optic tract axons emit collaterals to the LGd. During development, axons in both
      divisions of the optic tract emit collaterals to the LGd, but by postnatal day
      15, collaterals of internal optic tract axons are virtually entirely eliminated,
      whereas those of superficial optic tract axons have elaborated terminal arbors.
      Thus, the heterogeneity among different classes of RGCs with respect to their
      efferent connections emerges by the selective stabilization, by each class, of a
      unique subset of connections from an initially widespread set shared by all
      classes. Thalamic collaterals of RGC axons emerge along established axon trunks,
      not by bifurcation of the growing tip. This occurs after the axons have grown
      past the thalamus and, presumably, entered their targets in the midbrain. Growth
      cones at the tips of elongating axon trunks are larger in size and have a more
      "complex" morphology compared to the growth cones on collaterals. Axons of RGCs
      develop in 3 morphologically distinct growth states. First, they elongate to
      their most distant targets in the midbrain. Then, they simultaneously emit
      unbranched or poorly branched collaterals to multiple targets. Finally, they
      elaborate terminal arbors in their definitive targets and eliminate their other
      collaterals. This developmental strategy may be paradigmatic for the formation of
      long CNS pathways with multiple targets. Furthermore, these data document, at the
      single-axon level, the steps in the elaboration and withdrawal of transient
      neuronal projections.

PMID- 1992014
TI  - The early commitment of fetal neurons to the limbic cortex.
AB  - The limbic-system-associated membrane protein (LAMP) is expressed early in
      cerebral cortical development by migrating and postmigratory neurons in limbic
      regions such as the prefrontal and perirhinal cortices (Horton and Levitt, 1988),
      but not by nonlimbic neurons such as in the primary sensory and motor cortices.
      In the present study, we used LAMP expression to evaluate the timing and
      potential cell-lineage and environmental determinants of the commitment of
      cerebral cortical neurons to limbic and nonlimbic phenotypes. The cerebral wall,
      containing either presumptive perirhinal or sensorimotor cortex, was removed
      prior to [embryonic day (E) 12, 14] or just after (E17) the onset of LAMP
      expression, labeled with fast blue, and placed into cavities in either perirhinal
      or sensorimotor regions of postnatal day (P) 1 hosts. Host animals were allowed
      to survive until at least P10, and surviving transplanted cells were counted and
      evaluated for LAMP expression. Sensorimotor cortical neurons transplanted at E14
      or E17, in either homotopic or heterotopic locations, did not express LAMP. In
      contrast, a high percentage of perirhinal cortical neurons transplanted at either
      E14 or E17, whether situated in sensorimotor or perirhinal regions of the host,
      expressed the limbic marker protein. Surprisingly, neurons from E12 donors
      exhibited patterns of LAMP expression that reflected their new location in the
      host rather than their embryonic origin. The data suggest that there is an early
      pliant period in which precursor and early differentiating cells remain
      uncommitted to a particular cortical regional phenotype. After this period, one
      aspect of the molecular phenotype (determined by LAMP expression) of neurons
      destined for sensorimotor and allo- and mesocortical regions has become immutable
      by environmental factors in the host.

PMID- 1992015
TI  - A novel calmodulin antagonist, CGS 9343B, modulates calcium-dependent changes in
      neurite outgrowth and growth cone movements.
AB  - The neurotransmitter 5-HT alters growth cone motility and neurite elongation in
      neuron B19, isolated from the buccal ganglion of Helisoma trivolvis (Haydon et
      al., 1984). The effects of 5-HT are mediated by increases in intracellular
      calcium levels within the growth cones (Cohan et al., 1987). 5-HT causes a
      receptor-mediated depolarization of the membrane, which results in the opening of
      voltage-sensitive calcium channels. The resulting calcium influx decreases both
      the elongation rate and the total outgrowth of neurites. However, the
      mechanism(s) mediating these calcium-dependent changes is unclear. As many of the
      intracellular effects of calcium in eukaryotic cells are mediated by the calcium
      binding protein calmodulin, we tested the involvement of such an interaction in
      the regulation of neurite outgrowth. In these experiments, a new, potent
      calmodulin antagonist with increased selectivity, CGS 9343B (CGS; Norman et al.,
      1987), was used to inhibit calmodulin activity during the application of 5-HT to
      neuron B19. The addition of 100 microM 5-HT to the culture medium resulted in a
      significant decrease in the rate of neurite elongation and total neurite
      outgrowth. Administration of CGS to the culture medium at a concentration (1.8
      microM) equivalent to its IC50 for calmodulin inhibition completely blocked the
      inhibitory effects of 100 microM 5-HT, on both neurite elongation and total
      neurite outgrowth. CGS alone caused a slight decrease in elongation rate but had
      no significant effect on total outgrowth. CGS did not block 5-HT-induced
      electrical activity, indicating that it was not acting as a 5-HT receptor
      antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1992016
TI  - Characterization and localization of cannabinoid receptors in rat brain: a
      quantitative in vitro autoradiographic study.
AB  - A potent, synthetic cannabinoid was radiolabeled and used to characterize and
      precisely localize cannabinoid receptors in slide-mounted sections of rat brain
      and pituitary. Assay conditions for 3H-CP55,940 binding in Tris-HCl buffer with
      5% BSA were optimized, association and dissociation rate constants determined,
      and the equilibrium dissociation constant (Kd) calculated (21 nM by liquid
      scintillation counting, 5.2 nM by quantitative autoradiography). The results of
      competition studies, using several synthetic cannabinoids, add to prior data
      showing enantioselectivity of binding and correlation of in vitro potencies with
      potencies in biological assays of cannabinoid actions. Inhibition of binding by
      guanine nucleotides was selective and profound: Nonhydrolyzable analogs of GTP
      and GDP inhibited binding by greater than 90%, and GMP and the nonhydrolyzable
      ATP analog showed no inhibition. Autoradiography showed great heterogeneity of
      binding in patterns of labeling that closely conform to cytoarchitectural and
      functional domains. Very dense 3H-CP55,940 binding is localized to the basal
      ganglia (lateral caudate-putamen, globus pallidus, entopeduncular nucleus,
      substantia nigra pars reticulata), cerebellar molecular layer, innermost layers
      of the olfactory bulb, and portions of the hippocampal formation (CA3 and dentate
      gyrus molecular layer). Moderately dense binding is found throughout the
      remaining forebrain. Sparse binding characterizes the brain stem and spinal cord.
      Densitometry confirmed the quantitative heterogeneity of cannabinoid receptors
      (10 nM 3H-CP55,940 binding ranged in density from 6.3 pmol/mg protein in the
      substantia nigra pars reticulata to 0.15 pmol/mg protein in the anterior lobe of
      the pituitary). The results suggest that the presently characterized cannabinoid
      receptor mediates physiological and behavioral effects of natural and synthetic
      cannabinoids, because it is strongly coupled to guanine nucleotide regulatory
      proteins and is discretely localized to cortical, basal ganglia, and cerebellar
      structures involved with cognition and movement.

PMID- 1992017
TI  - Yttrium-90 for cancer therapy studies secured through Government and commercial
      suppliers.

PMID- 1992018
TI  - Long-term follow-up after heterotopic splenic autotransplantation for traumatic
      splenic rupture.
AB  - The trapping function of the heterotopic splenic autotransplants (HSA) in 13
      polytraumatized patients, aged 5-38 yr, was evaluated using heat damaged
      technetium-99m-labeled autologous red blood cells in early (1-7 mo) and late (3
      4.5 yr) period after heterotopic autotransplantation to the omentum. The
      intensity of tracer accumulation was graded in comparison to the liver uptake.
      The splenic tissue surface was calculated on anterior projection each time. The
      shapes of the transplants were compared and new uptake foci suggesting
      spontaneous splenosis were looked for on both scans. The average surface of HSA
      was 28.2 (+/- 14.7) cm2 on early and 44.1 (+/- 14.3) cm2 on late examination (p
      less than 0.003) and the increase in intensity of tracer accumulation on both
      occasions was significant as well (p less than 0.0001). In three patients, some
      additional splenotic foci were found on follow-up scans. Howell-Jolly bodies in
      peripheral blood were detected in six of eight patients in early and remained
      detectable in lower number in three of eight patients on follow-up. No serious
      infection was noticed in our group of patients. Our work confirmed the excellent
      survival rates of HSA with improving trapping function and no important spread
      from original implantation site on long-term follow-up.

PMID- 1992019
TI  - Compensatory splenic growth: role of functional indicators.

PMID- 1992020
TI  - Visual stimulation increases technetium-99m-HMPAO distribution in human visual
      cortex.
AB  - The ability of changes in the distribution of technetium-99m-hexamethylpropylene
      amine oxime (99mTc-HMPAO) to reflect physiologic changes in regional cerebral
      blood flow (rCBF) was evaluated using photic stimulation, a procedure known to
      increase rCBF in the striate cortex. Seven healthy subjects were injected with
      740 MBq 99mTc-HMPAO on two separate days. On one day, the injection was performed
      following closure of the eyes and patching for 5 min. On the other day, subjects
      were exposed to a stroboscopic light to produce photic simulation. Images of
      distribution of 99mTc-HMPAO were obtained using a Strichman 810X single-photon
      emission computed tomogram (SPECT) brain scanner. Comparison of images obtained
      during light occluded versus stimulation conditions revealed a significant
      increase in distribution of radiopharmaceutical in visual cortex relative to
      whole brain (peak increase corrected for radiopharmaceutical backdiffusion 36.7%
      +/- 6.6%). HMPAO appears to provide a useful method for detecting relative rCBF
      increases with SPECT.

PMID- 1992021
TI  - Normative data for lumbar spine bone mineral content in children: influence of
      age, height, weight, and pubertal stage.
AB  - In 136 normal growing children between the ages of 1 and 18 yr, bone mineral
      content (BMC) at the level of the lumbar spine (L2-L4) was determined with a
      commercial dual-photon absorptiometer. BMC was calculated as BML (BMC per unit
      length) and BMD (BMC per unit surface). The mean lumbar spine BML of the studied
      children (2.53 +/- 0.86 gHA/cm) was significantly lower than the spinal mineral
      content of adults (4.26 +/- 0.57 gHA/cm). No sex difference existed in lumbar
      spine BMC. BML as well as BMD were highly dependent on age, body height, and body
      weight. During the prepubertal years, BML and BMD increased in a fairly
      rectilinear pattern. During puberty, BMC increased more rapidly: 40% for BMD and
      77% for BML. For the entire group, the increase in BMC with age, height, and
      weight was best predicted by an exponential regression line analysis.

PMID- 1992022
TI  - Study relates economic status to death risk among radiation workers.

PMID- 1992024
TI  - DOE bestows Fermi Award upon nuclear medicine pioneer Robley Evans.

PMID- 1992023
TI  - Reproducibility of image interpretation in immunoscintigraphy performed with
      indium-111- and iodine-131-labeled OC125 F(ab')2 antibody injected into the same
      patients.
AB  - An important criterion for the clinical use of a new imaging technique is the
      correct reproducibility of interpretation. Forty-six paired immunoscintigraphic
      examinations were performed on 43 patients with suspected ovarian carcinoma
      recurrence using F(ab')2 fragments of OC125 antibody labeled first with indium
      111 and then with iodine-131. Planar scintigraphy (PS) and emission computed
      tomography (ECT) images were interpreted blindly and separately by three
      observers, and reproducibility was evaluated by a kappa concordance index. Intra-
      and interobserver reproducibility were generally satisfactory (kappa values of
      0.6 and 0.7, respectively). Binomial analysis of kappa values for ECT showed the
      superiority of indium-111 for intraobserver (p = 0.035) and interobserver (p =
      0.0039) study. However, for PS there was no significant difference in
      reproducibility with the two radionuclides.

PMID- 1992025
TI  - Assessment of myocardial perfusion in patients after the arterial switch
      operation.
AB  - In 21 patients who had undergone the arterial switch operation, the adequacy of
      myocardial perfusion was evaluated by thallium-201 computed scintigraphy 2.6 +/-
      2 (0.3-7) yr after surgery. Fourteen patients had undergone the arterial switch
      procedure after pulmonary artery banding and seven as a primary repair.
      Isoproterenol stress increased the heart rate by at least 55%. Tomographic
      imaging was performed at peak stress and 3 hr later in the reperfusion phase.
      Nine patients had perfusion defects. The perfusion defects were located at the
      left ventricular apex in four (with extension to the inferolateral wall in one),
      left ventricular anterolateral wall in two, ventricular septum in one, left
      ventricular inferior wall in one, and right ventricular free wall in one. Some of
      these defects could be due to myocardial damage at the time of surgery, but these
      results also raise concern about long-term adequacy of myocardial perfusion
      following the arterial switch procedure.

PMID- 1992026
TI  - Comparison of in vitro RBC labeling with the UltraTag RBC kit versus in vivo
      labeling.
AB  - This study compared cardiac-gated equilibrium blood-pool imaging studies using in
      vitro technetium-99m- (99mTc) labeled red blood cells (RBCs) prepared with the
      UltraTag RBC kit to in vivo labeling with stannous (pyro- and trimeta-)
      phosphates. The in vitro labeling procedure takes approximately 25 min and does
      not require centrifugation to separate free from bound 99mTc. Imaging studies
      were performed in 30 patients using the in vitro labeling procedure and in 30
      patients with in vivo labeling. Regions of interest were placed over the center
      of the left ventricle, inferior and lateral to the left ventricle (background),
      and over the right midlung. The mean +/- s.e. in vitro RBC labeling efficiency
      was 98.5 +/- 0.2%. The heart-to-background ratios were significantly higher with
      in vitro labeling. The heart-to-background ratios, averaged among two blinded
      reviewers, were 4.6 and 3.4 for the in vitro and in vivo methods, respectively.
      The heart-to-lung ratio was generally higher with the in vitro procedure (3.6)
      than that observed with the in vivo method (3.2) but failed to attain statistical
      significance (p = 0.059). These results demonstrate the superiority of the in
      vitro labeling procedure over in vivo labeling for gated equilibrium blood-pool
      imaging.

PMID- 1992027
TI  - Myocardial uptake of carbon-11-acetate as an indirect estimate of regional
      myocardial blood flow.
AB  - The rate of clearance of myocardial carbon-11 (11C) activity (after the
      administration of 11C-acetate) has been shown to correlate closely with
      myocardial oxygen consumption. In the present study, we hypothesized that
      regional net myocardial uptake of 11C-acetate, which reflects primarily delivery
      and extraction of tracer, would be markedly flow-dependent and potentially useful
      as an indirect index of regional myocardial blood flow. In 22 patients with
      stable coronary artery disease, the regional distribution of early net uptake of
      11C-acetate was correlated with estimates of regional myocardial blood flow
      assessed with oxygen-15-water. The myocardial images of 11C-acetate uptake were
      of high quality. The correlation between the two approaches was close (r = 0.88)
      and not affected by the metabolic state of the tissue. Thus, in patients with
      stable coronary artery disease, under resting conditions, direct estimates of
      myocardial oxygen consumption in relation to the level of delivery of tracer to
      the tissue can now be obtained by PET with use of a single radiopharmaceutical,
      11C-acetate. This approach may prove particularly useful in streamlining clinical
      protocols designed to assess myocardial oxygen consumption.

PMID- 1992028
TI  - Comparison of 1073 MBq and 3700 MBq iodine-131 in postoperative ablation of
      residual thyroid tissue in patients with differentiated thyroid cancer.
AB  - In a randomized prospective study, we compared the efficacy of low dose (1073
      MBq) and high dose (3700 MBq) iodine-131 administration in postoperative ablation
      of residual functioning thyroid tissue in 63 patients with differentiated thyroid
      cancer. We were unable to demonstrate any difference between the low- and the
      high-dose of radioactive iodine in scintigraphic ablation of remnant tissue. In
      81% (21/26) of the patients, 1073 MBq ablated after the first dose, 77% (21/26 +
      3/5 = 24/31) after the first plus second dose, and 69% (24/31 + 0/4 = 24/35)
      after the first, second, and third dose. Radioiodine (3700 MBq) ablated in 84%,
      73%, and 69% of the patients after respectively 1., 1. plus 2., and 1. plus 2.
      plus 3. dose. Forty percent of the patients ablated with the low dose and 44%
      ablated with the high dose had elevated thyroglobulin levels at the time of
      complete scintigraphic ablation. In conclusion, we did not find any difference
      between 3700 MBq and 1073 MBq iodine-131 as regard to number of doses needed for
      complete scintigraphic ablation of residual functioning thyroid tissue.

PMID- 1992029
TI  - Blood-pool radionuclide angiography in patients with a Novacor left ventricular
      assist device.
AB  - Blood-pool radionuclide angiography was used to investigate the left ventricular
      function in eight patients who received a Novacor assist device as a bridge-to
      cardiac transplantation. Studies were performed during maximal and minimal
      tolerated assist device flows. The left ventricular ejection fraction, volumes,
      cardiac output, and the pump ejection fraction were computer-assessed. All
      patients had severe left ventricular dilation and hypokinesis before insertion of
      the assist device, with a mean ejection fraction of 18% +/- 4% which improved to
      44% +/- 18% (p less than 0.01) during maximal assist device flows, but fell to
      25% +/- 15% (p less than 0.01) during minimal flows. The ventricular volumes
      became normal at maximal assist device flow but increased significantly (p less
      than 0.05) during minimal flow. The pump was well visualized and had an ejection
      fraction of 82% +/- 7%. These data indicate that this assist device effectively
      unloads the left ventricle. The deterioration in ejection fraction following
      decrease in assist device flow is in keeping with the dependency of these
      patients on the device to sustain adequate hemodynamics.

PMID- 1992030
TI  - Effect of aortic sclerosis on bone mineral measurements by dual-photon
      absorptiometry.
AB  - Measurements of the bone mineral content (BMC) of lumbar spine by dual-photon
      absorptiometry (DPA) are performed mainly in the anteroposterior (AP) projection.
      Due to superimposition of the abdominal aorta, the BMC measured for patients with
      aortic calcification usually is too high. To determine the influence of aortic
      calcifications, DPA scans were performed in the AP-projection on 100 dissected
      abdominal aortae with different degrees of atherosclerosis placed on a human
      lumbar spine cast in lucite. The measured values were compared with those
      obtained in the same projection without the aortae. The average increase of the
      BMC values relative to the mean for the vertebrae L2 to L4 for aortae with severe
      complicated lesions, i.e., those containing larger amounts of calcium, was 0.03
      g/cm2, with a maximum deviation of 0.09 g/cm2. Aortae with fatty streaks or
      fibrous plaques did not cause significant increases of the BMC. The mean
      deviation for aortae with mild complicated lesions, i.e., those containing
      smaller amounts of calcium, was within the range of instrument precision.

PMID- 1992031
TI  - Early scintigraphic detection of experimental myocardial infarction in dogs with
      technetium-99m-glucaric acid.
AB  - Recent data have generated some interest in technetium-99m-(99mTc) glucaric acid
      as an in vivo viability marker. We studied 99mTc-glucaric acid retention in
      canine models of myocardial ischemia (20-min occlusion of the LAD/40-min
      reperfusion), acute myocardial infarction (MI) (90-min LAD occlusion/3-hr
      reperfusion), and chronic MI (90-min occlusion and either 48-hr or 10-day
      reperfusion). Regional myocardial blood flow was measured by radiolabeled
      microspheres. No preferential uptake of glucaric acid was observed in ischemic
      but viable myocardium. The compound showed high affinity for necrotic myocardial
      tissue for several days following injury. The preferential uptake in infarcted
      tissue disappeared by 10 days following injury. This study shows that 99mTc
      glucaric acid acts exclusively as a marker of necrosis in canine models of MI.
      Technetium-99m-glucaric acid may have clinical utility in early cardiac imaging
      of myocardial infarction and in differentiating recent from old injuries.

PMID- 1992032
TI  - Variables influencing tumor uptake of anti-melanoma monoclonal antibodies
      radioiodinated using para-iodobenzoyl (PIB) conjugate.
AB  - Tumor uptake was examined with respect to antigen expression, time-dependent
      biodistribution, dose of Mab injected, tumor size, and tumor site (i.e.,
      subcutaneous versus lung or liver metastases). NR-ML-05, 96.5, and P94 showed
      significantly greater uptake in subcutaneous tumors than CL207 and 5.1 (p less
      than 0.05). NR-ML-05 had a significantly higher tumor uptake at 24 hr (11.9 +/-
      0.51) than at 72 hr (4.0 +/- 0.37) or 144 hr (2.7 +/- 0.84) after injection (p
      less than 0.001). The other four Mabs had similar tumor distribution at all three
      time points. The tumor uptake of four Mabs (96.5, P94, CL207. 5.1) differed with
      respect to in vitro versus in vivo binding to tumor, tumor type, dose of Mab, and
      tumor site (subcutaneous versus metastases). In contrast, NR-ML-05 demonstrated
      consistent uptake in tumors independent of the above parameters. These data
      suggest that certain host parameters can influence in vivo tumor targeting
      depending on characteristics of each Mab studied.

PMID- 1992033
TI  - Biologic characterization of melanoma tumors by antigen-specific targeting of
      radiolabeled anti-tumor antibodies.

PMID- 1992034
TI  - Metabolic imaging with gallium-68- and indium-111-labeled low-density
      lipoprotein.
AB  - Low-density lipoprotein (LDL) labeled with either gallium-68 (68Ga) or indium-111
      (111In) was evaluated as a potential PET or SPECT radiopharmaceutical for
      determination of hepatic lipoprotein metabolism in rabbits. Gallium-68 or 111In
      was linked to LDL via diethylenetriaminepentaacetic acid (DTPA) with a 25-70%
      radiochemical yield. Studies in vivo that compared 68Ga- or 111In-DTPA-LDL with
      dilactitol-[125I]-tyramine LDL and 131I-LDL showed that both 68Ga- and 111In
      labeled LDL behaved as residualizing radiotracers. Localization of radioactivity
      within the liver of normal rabbits was visualized clearly with [68Ga]DTPA-LDL by
      PET and with [111In]DTPA-LDL by gamma scintigraphy. Significant differences were
      observed in hepatic uptake of normal compared with hypercholesterolemic rabbits
      in which low-capacity LDL receptor-mediated catabolism was saturated. Gallium-68
      and 111In-DTPA-LDL are attractive radiopharmaceuticals for noninvasive
      delineation of tissue LDL metabolism under normal and pathophysiologic
      conditions.

PMID- 1992036
TI  - Myocarditis simulating myocardial infarction.

PMID- 1992035
TI  - Imaging histamine H1 receptors in the living human brain with carbon-11
      pyrilamine.
AB  - The brain distribution and kinetics of the H1 receptor antagonist, carbon-11
      pyrilamine (11C-pyrilamine) were examined in vivo in two baboons and one human by
      positron emission tomography. After i.v. administration of the tracer, brain
      activity peaked within 20 min after injection and subsequently decreased,
      reflecting reversible binding to the receptor. Pretreatment with 1 mg/kg
      diphenhydramine reduced the brain activity at 70 min by 33%, 29%, 26%, and 23% of
      the control values in frontal cortex, temporal cortex, hippocampus, and
      cerebellum, respectively. Coinjection of 1 and 5 mg/kg cold pyrilamine reduced
      the activity at 70 min by 40%, 36%, 34%, and 30% in frontal, temporal,
      hippocampus and cerebellum, respectively. The in vivo specific binding to the H1
      receptors in different brain regions at 70 min after injection correlated with
      the in vitro H1 histamine receptors distribution in human brain tissue obtained
      at autopsy, with high values in the frontal and temporal cortex and low values in
      cerebellum and brain stem. In the healthy human volunteer study, the value of
      washout of radioactivity increased by about 50% after injection of 0.7 mg/kg
      diphenhydramine.

PMID- 1992037
TI  - Technetium-99m-methylene diphosphonate (MDP) uptake in a sympathetic effusion: an
      index of malignancy and a review of the literature.
AB  - We report a patient with a sympathetic pleural effusion secondary to T-cell
      lymphoma that accumulated the bone imaging agent, Technetium-99m-methylene
      diphosphonate (99mTc-MDP). This case is significant in that malignant cells were
      not present on three cytologic examinations of the pleural fluid or multiple
      pleural biopsies. We also present a review of the published literature on pleural
      effusions that accumulate bone tracers. We conclude that pleural effusions that
      accumulate 99mTc-MDP should be considered malignant or secondary to a malignancy
      and further work-up is essential even if the cytologic exam of the pleural fluid
      is unremarkable.

PMID- 1992039
TI  - Delayed positive gastrointestinal bleeding studies with technetium-99m-red blood
      cells: utility of a second injection.
AB  - Two patients studied with technetium-99m-labeled red blood cells (RBCs) for
      gastrointestinal bleeding had positive findings only on 24-hr delayed images, at
      which time the site of bleeding could not be ascertained. In each instance, when
      additional delayed images suggested that active bleeding was occurring, a second
      aliquot of RBCs was labeled and injected. Sites of active hemorrhage were
      identified following further imaging in both patients. When delayed GI bleeding
      images are positive, further views should be obtained to ascertain if the pattern
      of intraluminal activity changes. If renewed active hemorrhage is suspected,
      reinjection with a second dose of labeled RBCs may identify the bleeding site.

PMID- 1992038
TI  - Gallium uptake in tryptophan-related pulmonary disease.
AB  - We describe a patient who developed fever, fatigue, muscle weakness, dyspnea,
      skin rash, and eosinophilia after taking "high doses" of tryptophan for insomnia
      for two years. A gallium-67 scan revealed diffuse increased uptake in the lung
      and no abnormal uptake in the muscular distribution. Bronchoscopy and biopsy
      confirmed inflammatory reactions with infiltration by eosinophils, mast cells,
      and lymphocytes. CT scan showed an interstitial alveolar pattern without
      fibrosis. EMG demonstrated diffuse myopathy. Muscle biopsy from the right thigh
      showed an inflammatory myositis with eosinophilic and lymphocytic infiltrations.

PMID- 1992040
TI  - Three-dimensional simulations of multidetector point-focusing SPECT imaging.
AB  - We have applied an efficient algorithm for mathematically simulating the three
      dimensional (3-D) response of a SPECT imaging system with a depth-dependent 3-D
      point spread function (3-DPSF). The input object whose reconstructed image is to
      be simulated is restricted to a binary map; more complex objects may be treated
      as linear combinations of binary maps. The 3-D convolution reduces to a sequence
      of additions of a 3-D line spread function (3-DLSF), appropriately translated, to
      the 3-D response. We have simulated the projection data from a multidetector
      SPECT system with point-focusing collimators. The simulated projection data were
      then reconstructed using the manufacturer's software. The objects simulated
      included simple geometrical solids such as spheres and cylinders, as well as the
      distribution of muscarinic cholinergic receptors in a realistic brain slice. The
      results of these simulations indicate the existence of significant qualitative
      and quantitative artifacts in reconstructed human brain images.

PMID- 1992041
TI  - Determination of weighting functions for energy-weighted acquisition.
AB  - Energy-weighted acquisition (EWA) is an image filtering technique, with a
      different spatial filter (weighting function) for each energy. The imaging
      characteristics of EWA are governed by the weighting functions used during the
      acquisition of the image. The determination of weighting functions is more
      complicated than the determination of energy windows in conventional imaging
      because the number of degrees of freedom is much greater. A methodology by which
      weighting functions can be produced is described. The weighting function is
      determined by minimizing a generalized chi-square with variable contributions
      from coefficients quantifying key image characteristics, e.g., signal-to-noise
      ratio, spatial resolution, and scatter fraction. Varying the importance of these
      characteristics gives us a workable function-generation tool, able to address a
      variety of clinical needs. The resulting weighting functions exhibit good scatter
      reduction properties at various scatter depths, as demonstrated by measurements
      of line source response functions in a scattering medium at depths from 5 to 14
      cm. Energy weighting can also be used to compensate for collimator penetration
      from high energy gamma rays. Weighting functions are tested in the laboratory
      using both planar and SPECT phantoms.

PMID- 1992042
TI  - Radiation hormesis.
AB  - "Radiation hormesis" is the name given to the putative stimulatory effects of low
      level ionizing radiation (generally in the range of 1-50 cGy of low-LET
      radiation). Based on historical and pharmacologic principles reminiscent of some
      of the major tenets of homeopathy, most of these effects are now generally
      ascribed to protective feedback systems that, upon exposure to low concentrations
      of toxins, proceed to stimulate metabolic detoxification and repair networks. The
      activation of these networks may then result in net beneficial effects on the
      cell, organism or species. Discussions of possible stimulatory effects of low
      levels of ionizing radiation have recently become entangled with the separate but
      related question of whether a threshold dose level exists on the radiotoxicologic
      dose-response curve. This review summarizes some of the relevant historical and
      scientific data bearing on the question of radiation hormesis. We find the data
      in support of most of the hormesis postulates intriguing but inconclusive.

PMID- 1992043
TI  - Iodine-125-MIBG therapy for neuroblastoma.

PMID- 1992044
TI  - Effective background correction on separate technetium-99m-DTPA renal clearance.

PMID- 1992045
TI  - Thyroidal absorbed dose from a standard five-millicurie iodine-131 (185 MBq) dose
      for thyrotoxicosis: cure can occur with less than the conventional 7000 rads.

PMID- 1992046
TI  - Biotin deficiency per se is teratogenic in mice.
AB  - We examined whether maternal biotin deficiency would potentiate the latent
      teratogenicity of relatively low doses of vitamin A in mice. The incidence and
      the type of gross congenital malformations (cleft palate, micrognathia, and
      micromelia) induced by biotin deficiency were similar among the groups given
      three different concentrations of vitamin A (4000, 12,000 and 60,000 IU) in the
      diet. Also, the type of these malformations was different from those
      (exencephaly, cleft palate and macroglossia) induced by a known teratogenic dose
      of vitamin A (1,200,000 IU). We conclude that in mice concentrations of vitamin A
      in the range of 4-10 times the level recommended by the National Research Council
      and biotin deficiency do not interfere with one another; also, biotin deficiency
      per se is teratogenic in mice.

PMID- 1992047
TI  - A high yield preparation of brush border membrane vesicles from organ-cultured
      embryonic chick jejunum: demonstration of insulin sensitivity of Na(+)-dependent
      D-glucose transport.
AB  - Although embryonic chick small intestinal segments provide a very limited amount
      of tissue for preparation of enterocyte brush border membrane vesicles (BBMV), we
      were able to develop a procedure for isolation of BBMV from cultured 20-d-old
      embryonic chick jejunum in high yield by modifying a divalent cation
      precipitation method. Total yield of the brush border marker enzyme alkaline
      phosphatase in the vesicle fraction as compared to the crude homogenate was
      approximately 40%, and the specific activity of the enzyme was increased 25-fold
      on the average. The brush border membrane vesicle fraction was only contaminated
      with other cellular organelles (basolateral membranes, mitochondria, lysosomes or
      endoplasmic reticulum) to a minor extent. Functional integrity of the brush
      border vesicles was indicated by Na+ gradient-driven electrogenic D-glucose
      transport leading to concentrative transfer (overshoot) of the sugar into an
      osmotically active intravesicular space. When jejuna were cultured for 48 h in
      the presence of 10(-6) mol/L insulin, the initial rate of Na(+)-dependent D
      glucose uptake by brush border membrane vesicles as well as Na(+)-dependent
      [3H]phlorizin binding to brush border membranes was approximately twice as high
      as in vesicles from untreated controls. This strongly suggests that insulin could
      enhance intestinal absorption of D-glucose by increasing the intrinsic activity
      of the Na(+)-dependent D-glucose transport system at the luminal membrane of
      enterocytes.

PMID- 1992049
TI  - Effect of ascorbic acid nutriture on blood histamine and neutrophil chemotaxis in
      guinea pigs.
AB  - Histamine suppresses certain immune responses, including neutrophil chemotaxis.
      The present study examined whether the histamine-lowering effect of ascorbate was
      accompanied by enhanced chemotaxis in guinea pigs. Animals were fed low
      ascorbate, adequate or high ascorbate diets (0.5, 2.0 or 50 mg ascorbate.100 g
      body wt-1.d-1) for 4 wk. Mean liver ascorbate paralleled dietary intake, and
      these values differed significantly. Blood histamine was significantly depressed
      in the high ascorbate group compared to the adequate and low ascorbate groups,
      and liver ascorbate was inversely correlated to blood histamine levels (r = 
      0.64, P less than 0.001). The random migration of neutrophils was not
      significantly affected by vitamin dosage. Leukocyte chemotaxis was significantly
      impaired in low ascorbate animals compared to that of animals with adequate
      ascorbate nutriture. Leukocyte chemotaxis in high ascorbate animals did not
      differ significantly from that in the adequate or low ascorbate groups.
      Furthermore, chemotaxis was significantly lower when cells extracted from animals
      with adequate ascorbate nutriture were incubated in low ascorbate or high
      ascorbate serum rather than in autologous serum. These data suggest that the
      histamine-lowering effect of supplemental ascorbate does not appear to enhance
      leukocyte chemotaxis and that serum from guinea pigs fed low or high levels of
      ascorbate appears to contain factors that depress chemotaxis.

PMID- 1992048
TI  - Dietary regulation of intestinal glycosyl-transferase activities: relation
      between developmental changes and weaning in rats.
AB  - Activities of rat intestinal fucosyl-transferase (GDP-fucose: glycoprotein
      fucosyl-transferase; EC 2.4.1.68) and sialyl-transferase (N-acetylneuraminyl
      transferase; EC 2.4.99.1) respectively exhibited a significant increase following
      weaning and a steady decrease between birth and weaning. The variations of the
      two glycosyl-transferase activities with age could not be explained by the
      presence of inhibitory factors in microsomes or cytosol, nor were they due to a
      natural modification of the milk composition at the end of lactation. The
      increase in fucosyl-transferase activity that followed weaning was prematurely
      induced by early weaning. Prolonged nursing prevented the normal increase in
      fucosyl-transferase activity, and late weaning delayed the increase. The
      sensitivity to the modification of the time of weaning indicated a major effect
      of dietary changes, related to the introduction of a solid carbohydrate-rich
      diet, on the developmental pattern of this enzyme. However, a stress response
      could not be excluded after early weaning since the corticosterone level of the
      early weaned rats was enhanced as compared to that of suckling rats. For sialyl
      transferase, early weaning caused a slightly greater than normal decrease in the
      activity, whereas prolonged nursing only weakly diminished the normal decrease in
      the activity. Moreover, late weaning had no effect on the sialyl-transferase
      activity. The age-related variations of this enzyme likely are due to factors
      independent of diet. Thus, the developmental variations of the fucosyl- and
      sialyl-transferases appear to be differently regulated.

PMID- 1992050
TI  - Magnesium absorption: mechanisms and the influence of vitamin D, calcium and
      phosphate.
AB  - Magnesium absorption has been studied in both humans and animals under diverse
      experimental conditions. As a result, the data often appear confusing and
      conflicting. In this review we attempt to summarize information concerning Mg
      absorption and, where possible, to reconcile apparently conflicting observations.
      Most studies suggest that Mg is absorbed predominantly in the distal intestine.
      At usual Mg intakes, Mg absorption occurs primarily by intercellular diffusional
      and solvent drag mechanisms. There is evidence for a saturable component of Mg
      absorption in the small intestine and the descending colon that is important at
      low dietary Mg intakes. Pharmacological doses of vitamin D increase Mg absorption
      in both vitamin D-deficient and vitamin D-replete animals. A substantial amount
      of Mg absorption, however, occurs independent of vitamin D. In addition, vitamin
      D may reduce Mg retention through increases in urinary Mg excretion. Intestinal
      interactions between Mg and calcium or phosphate have been demonstrated in both
      humans and animals. The nature of these interactions cannot be readily explained
      by data currently available.

PMID- 1992051
TI  - Dietary selenium and antioxidant status: toxic effects of 1,2-dimethylhydrazine
      in rats.
AB  - Weanling male Sprague-Dawley rats were used to determine whether the mechanism of
      the previously reported toxicity of 1,2-dimethylhydrazine (DMH) in selenium
      deficient rats was related to a diminished capacity for detoxification of
      reactive oxygen species via glutathione peroxidase (GSH-Px) as well as by other
      known pathways of detoxification, including catalase (CAT), superoxide dismutase
      (SOD), glutathione-S-transferase (GST) and levels of glutathione (GSH). A 3 x 3
      factorial experimental design was used to examine the acute effects of DMH
      treatment (0, 10 and 20 mg/kg body weight) interacting with dietary Se levels
      (less than 0.02, 0.1 and 0.5 mg/kg diet as sodium selenite). Animals were
      maintained on the test diets for 4 wk prior to challenge with DMH. Preliminary
      kinetics studies indicated the most appropriate time to examine antioxidant
      status was 3 h after DMH injection. At that time, livers and colons were analyzed
      for tissue levels of GSH-Px, CAT, SOD, GST and GSH. Data analysis demonstrated
      that Se deficiency impaired the ability of both liver and colon to mount an
      induced detoxification response to the acute oxidative stress generated by DMH
      challenge and may explain the toxicity of DMH in Se-deficient rats.

PMID- 1992052
TI  - Protein evaluation, amino acid scoring and the Food and Drug Administration's
      proposed food labeling regulations.

PMID- 1992053
TI  - Does dietary protein increase urinary calcium?

PMID- 1992055
TI  - Medium- and long-chain triglycerides labeled with 13C: a comparison of oxidation
      after oral or parenteral administration in humans.
AB  - The special physical properties of medium-chain triglycerides (MCT) result in
      some substantial differences in their metabolism compared to that of long-chain
      triglycerides (LCT). Administering MCT is of importance in enteral nutrition of
      patients with disturbances of fat digestion or lipoprotein lipase deficiency.
      Their use in parenteral nutrition is also of interest. The purpose of this study
      was to compare the rate of conversion of MCT and LCT to CO2 after parenteral or
      oral administration in humans. At 1-wk intervals, a liquid formula diet (418 kJ/h
      for 8 h) was given to five healthy volunteers following an overnight fast. Two
      hours after starting this, they were given either 100 mg [13C]trioctanoate or
      [13C]trioleate orally or parenterally. Excess 13C in breath carbon dioxide was
      analyzed by mass-spectrometry, and oxidation rates over 7.5 h were calculated.
      Oxidation rates for [13C]trioctanoate were on the average 34.7% after enteral and
      31.0% after parenteral administration, and for [13C]trioleate, 25.3 and 24.9%,
      respectively (p less than 0.05, trioctanoate vs. trioleate). The results show
      that the oxidation of trioctanoate in healthy humans is greater both after oral
      and parenteral administration and increases more rapidly than that of
      [13C]trioleate.

PMID- 1992054
TI  - Effect of chronic glucagon administration on the metabolism of triacylglycerol
      rich lipoproteins in rats fed a high sucrose diet.
AB  - Male adult Wistar rats were fed a semipurified diet rich in sucrose (53 g/100 g
      diet). The effects of chronic glucagon administration (20 micrograms.day-1.rat-1,
      for 21 d) were studied on plasma lipid levels, triacylglycerol secretion rates
      and fractional catabolic rates determined by the intravenous fat tolerance test.
      Triacylglycerol secretion rates of plasma, chylomicron and very low density
      lipoprotein (VLDL) were measured by using the Triton WR 1339 method. In both
      fasting and postprandial states, the different rates were not significantly
      modified by glucagon treatment. However, in the treated animals, significantly
      decreased triacylglycerol concentrations were observed in plasma and VLDL during
      fasting (-41 and -46%, respectively) and also in chylomicrons in the postprandial
      state (-37%) relative to control animals. These data could be accounted for by an
      increased removal rate of triacylglycerol-rich lipoprotein. The estimated values
      of fractional rate constants (Triton WR 1339 experiment) were increased for VLDL
      (+62%) in the fasting state and for chylomicrons (+104%) in the postprandial
      state. Similarly, the fractional catabolic rate determined with the intravenous
      fat tolerance test (Intralipid, Kabivitrum, Sweden) was increased 49% by glucagon
      treatment, suggesting an effect of glucagon on the catabolism of triacylglycerol
      rich lipoproteins. Glucagon treatment did not modify the composition of VLDL
      obtained 60 min after Triton WR 1339 injection, except that in the fasting state
      apo B100 proportions and concentrations increased, suggesting a specific effect
      on the hepatic secretion of apo B100 VLDL.

PMID- 1992056
TI  - Physiological effects of retrograded, alpha-amylase-resistant cornstarch in rats.
AB  - Retrograded amylose was prepared by gelatinization of high amylose cornstarch,
      followed by storage at 1 degrees C for 48 h. The insoluble residue, which
      resisted hydrolysis with porcine amylase, was dried and fed to male Wistar rats
      for 14 d in powdered semisynthetic diet. Control rats received a similar diet
      containing sucrose in place of resistant starch. Fecal collections were performed
      throughout the feeding period. After 14 d the animals were killed. The small
      intestine and cecum were removed for morphological examination, measurement of
      small intestinal crypt cell production rate (CCPR) and analysis of luminal
      carbohydrate content. Blood samples were collected for analysis of cholesterol,
      glucagon, and enteroglucagon. In the starch-fed rats, fecal bulk and excretion of
      starch were higher than in the controls, but they declined markedly over the
      feeding period. Cecal size and contents were also greater in the starch-fed rats,
      and cecal pH was significantly lower. The CCPR was 66% higher in the ileum of the
      starch-fed rats (P less than 0.001), but there was no difference in the jejunum.
      There were no differences in serum cholesterol or enteroglucagon levels. We
      conclude that retrograded amylose is partially degraded in the alimentary tract
      of rats, but it contributes significantly to fecal bulk.

PMID- 1992057
TI  - Comparative antioxidant effectiveness of dietary beta-carotene, vitamin E,
      selenium and coenzyme Q10 in rat erythrocytes and plasma.
AB  - Five groups of five weanling rats were each fed a Torula yeast-based diet either
      unsupplemented or supplemented with 30 mg beta-carotene/kg, 30 IU vitamin E/kg, 1
      mg selenium/kg or 30 mg coenzyme Q10/kg. Elevated levels of plasma aspartate
      aminotransferase and alanine aminotransferase are sensitive indicators of liver
      damage. The former enzyme was lower (P less than 0.01) in the vitamin E-,
      selenium- and beta-carotene-supplemented groups than in the unsupplemented
      control group, and the latter enzyme was lower in the vitamin E- and selenium
      supplemented groups, suggesting a relatively equal effectiveness of these three
      antioxidants against liver damage. Erythrocytes were tested for protection
      against uninduced oxidative damage or that induced by 1 mmol/L
      bromotrichloromethane (BrCl3C) by measuring thiobarbituric acid-reactive
      substances (TBARS), hemoglobin, hemolysis, protein precipitation, alanine release
      and several enzyme activities. In untreated erythrocytes, selenium, beta-carotene
      and coenzyme Q10 exhibited protection by lowering (P less than 0.05) TBARS and
      alanine release, but only vitamin E protected against hemolysis. In BrCl3C
      treated erythrocytes, vitamin E, selenium and beta-carotene protected by
      decreasing (P less than 0.05) protein precipitation, whereas selenium and beta
      carotene decreased alanine release. The results of this study suggested that, in
      a manner analogous to vitamin E and selenium, beta-carotene and coenzyme Q10
      function as antioxygenic nutrients.

PMID- 1992059
TI  - Modulation by dietary vitamin E of I-compounds (putative indigenous DNA
      modifications) in rat liver and kidney.
AB  - I(indigenous)-compounds are age-related, carcinogen adduct-like, putative
      indigenous DNA modifications detectable by 32P-postlabeling assay in untreated
      animals. To investigate the origins of these DNA derivatives, we examined the
      effects of dietary vitamin E, a natural antioxidant, on I-compounds of rat liver
      and kidney DNA. Weanling female Sprague-Dawley rats were fed Draper's diets
      containing 0, 100, 1000, or 10,000 mg/kg alpha-tocopheryl acetate for 6 mo. The
      DNA from four individual rats of each group was analyzed by a nuclease P1
      enhanced version of the 32P-postlabeling assay for DNA adducts. The amount of
      vitamin E in the liver was measured by high performance liquid chromatography.
      Rats fed vitamin E-deficient diet (0 mg/kg) showed identical profiles and similar
      levels of I-compounds as those fed the 100 mg/kg diet. Most I-spots were
      significantly intensified and one tissue-specific extra spot was found in both
      liver and kidney DNA of rats fed the 1000 or 10,000 mg/kg vitamin E diet.
      However, one of the five major I-spots detected in the kidney was weaker in the
      1000 and 10,000 mg/kg groups than in the 0 and 100 mg/kg groups. These results
      show that formation of most I-compounds was not affected by vitamin E-deficient
      diet, and that long-term feeding of diet containing high levels of vitamin E may
      cause metabolic alterations leading to an increased formation of DNA-reactive
      (potentially mutagenic or carcinogenic) electrophiles.

PMID- 1992058
TI  - Characterization of ascorbic acid uptake by isolated rat kidney cells.
AB  - Isolated kidney cells accumulated L[1-14C]ascorbic acid in a time-dependent
      manner and reached a steady state after 15 min at 37 degrees C. Initial velocity
      for uptake was over 300 pmol/mg protein per min when cells were separated from
      the bathing solution using a density gradient established during centrifugation.
      The uptake process was saturable with an apparent concentration at half maximal
      uptake of 36 mumols/L. Ascorbate uptake was reduced by metabolic inhibitors and
      was temperature dependent. Although ascorbic acid is an acid anion at pH 7.4,
      uptake did not appear to be inhibited by other acid anions such as p
      aminohippurate and probenecid; however, involvement of the ion gradient
      established by Na+, H(+)-adenosine triphosphatase could not be confirmed.
      Replacing the sodium ion with other monovalent ions reduced the accumulation of
      ascorbate significantly. Isoascorbic and dehydroascorbic acids inhibited
      ascorbate uptake (34 and 13 mmol/L, respectively), whereas high concentrations of
      glucose showed some stimulation. These findings indicated that ascorbic acid is
      reabsorbed by the kidney in a sodium-dependent active transport process that is
      not common to other acid anions and has some specificity for the ascorbic acid
      structure.

PMID- 1992060
TI  - In vivo kinetics of intestinal absorption of riboflavin in rats.
AB  - To investigate absorption kinetics of riboflavin under in vivo conditions, with
      blood and lymph circulation intact, the small intestine of anesthetized rats was
      perfused with [14C]riboflavin in a concentration range between 0.31 and 10.00
      mumol/L. Apart from the uptake of riboflavin from the perfusate, passage of the
      vitamin into the portal (vena portae) and peripheral (vena femoralis) blood was
      determined. The absorption proved to be a dual process: at low substrate
      concentrations (less than 2 mumol/L) a saturable component predominated; at
      higher concentrations simple diffusion was found to be the prevailing uptake
      mechanism. The apparent transport constant of the saturable component was
      calculated to be 0.38 mumol/L. [14C]flavin concentrations in the portal and
      peripheral blood were estimated as a function of the riboflavin concentration of
      the perfusion media. The dual character of the absorption was reflected by the
      portal blood flavin levels. Due to the high retaining and equalizing capacity of
      the liver, the [14C]flavin level of the peripheral blood was relatively low and
      obeyed saturation kinetics. Constants of elimination, determined by
      pharmacokinetic calculations, were different for the two blood compartments but
      independent of the concentration of riboflavin in the perfusion media.

PMID- 1992061
TI  - Effect of chemical form of selenium on tissue glutathione peroxidase activity in
      developing rats.
AB  - Two experiments were conducted to determine the effect of various forms of
      selenium (Se) on the activity of glutathione peroxidase (GSHPx) in liver, heart,
      kidney and eyes of the developing rat. In experiment 1, throughout mating,
      pregnancy and lactation, female rats consumed one of three diets: basal (less
      than 0.05 microgram Se/g); selenite (0.15 microgram Se/g) and selenomethionine
      (0.15 microgram Se/g). Some pups born to dams in the basal group were also given
      intraperitoneal doses of saline, selenite or selenomethionine. GSHPx activity was
      measured in tissues from fetuses, 7-d-old and 14-d-old nursing pups and the dams.
      In all tissues studied, GSHPx activity was highest in the 14-d-old pups whose
      mothers were in the selenomethionine group. Rat pups given intraperitoneal
      selenite (3 micrograms/kg body weight) had higher liver and kidney GSHPx activity
      than pups given the same amount of selenium as intraperitoneal selenomethionine.
      In experiment 2, all dams were fed the same basal diet, and pups were weaned to
      diets containing one of two levels of selenium (0.1 or 0.2 microgram/g), one of
      three forms of selenium (selenite, selenomethionine or selenocystine) or no added
      selenium. After 14 d of repletion, the highest level of hepatic GSHPx activity
      occurred in the selenite group and the lowest in the basal diet group. After 21 d
      of repletion, renal GSHPx activity was lowest in the basal group followed by the
      selenocystine group. The highest tissue selenium concentration was found in
      kidney tissues of the selenocystine group. These data support the hypothesis that
      these dietary forms of selenium are differentially available for GSHPx activity.

PMID- 1992062
TI  - Effect of ethanol on cadmium uptake and metabolism of zinc and copper in rats
      exposed to cadmium.
AB  - Effects of chronic administration of cadmium and ethanol, alone as well as in
      combination, on the uptake of cadmium and its interaction with other essential
      trace elements in various tissues of adult rats were investigated. Cadmium given
      in combination with ethanol led to a pronounced increase in cadmium absorption
      and accumulation in all the tissues studied relative to both non-exposed controls
      and rats treated with cadmium alone. Both cadmium and ethanol exhibited specific
      effects on copper and zinc levels of the tissues. These effects often were
      significantly altered when the animals were co-exposed to cadmium and ethanol.
      The results suggested that although both cadmium and ethanol individually pose a
      hazard to essential trace metal homeostasis of various organs, co-exposure can
      pose a major threat since animals exposed to ethanol absorb much more cadmium
      than their unexposed counterparts.

PMID- 1992063
TI  - Mucus and iron absorption regulation in rats fed various levels of dietary iron.
AB  - We tested two hypotheses: (1) that iron binding by secreted mucus enhances iron
      absorption (Quarterman, Digestion 37: 1, 1987) and (2) that iron binding by
      secreted mucus prevents excess iron absorption. Rats were fed diets containing 6,
      200 or 500 mg Fe/kg diet (Fe-0, Fe-200 and Fe-500 rats, respectively) for 3 wk.
      Iron absorption was measured in fasted rats using 59FeCl3 in a 10-min in situ
      duodenal ligated-segment procedure. After draining the segment contents, the
      mucus layer was separated from the under-lying mucosal surface using Quarterman's
      agar cast technique. In comparison with that in Fe-200 rats, iron absorption in
      Fe-0 rats was markedly increased, but the 59Fe and the total mucus in the mucus
      layer were decreased. The 59Fe absorption and total mucus and total iron in the
      mucus layer were similar in Fe-500 rats and Fe-200 rats, but the 59Fe in the
      mucus layer was marginally lower in Fe-500 rats. There was no evidence that mucus
      enhanced iron absorption; it appeared to trap or bind iron proportionally to the
      amount of secreted mucus, suggesting protection against excess absorption. Mucus
      secretion and possibly synthesis were decreased in the Fe-0 rats.

PMID- 1992064
TI  - Age-related changes in the human femoral cortex.
AB  - Bone undergoes structural changes with aging, but the nature of qualitative
      changes remains to be established. Blocks of midshaft femur were taken at autopsy
      from men of four different age groups: 20-25 years, 40-45 years, 60-65 years, and
      80-85 years. Each femoral specimen was analyzed by density fractionation, a
      technique that allows the separation of bone by extent of mineralization and
      maturity. In the 20-25 group, lower density bone predominates. The 40-45 group is
      characterized by more highly mineralized bone with an increase in the 2.1-2.2
      g/cc fraction. At 60-65 years, an increase in the lower density fraction was
      found, indicating an increase in new bone formation. At 80-85 years, there is an
      increase in the highest density bone (2.2-2.3 g/cc), which may represent regions
      of interstitial bone not properly removed through remodeling processes. Chemical
      studies did not reveal any change in Ca, P, Ca + PO4, or Ca/P molar ratio with
      respect to age. X-ray diffraction studies show no changes in apatite crystal size
      with respect to age or degree of mineralization. Morphological studies documented
      increased remodeling activity and endosteal trabecularization in the older age
      groups, as well as increased intracortical porosity. An increase in the highest
      density fraction with aging may represent a pool of bone mineral that is less
      accessible to remodeling, which may be the interstitial bone.

PMID- 1992065
TI  - Heterogeneity of blood flow in tibial cortical bone: an experimental
      investigation using microspheres.
AB  - The distribution of tibial blood flow was measured by injecting approximately
      (600-1000) x 10(3) 15 mu microspheres, labelled with either tin-113 (113Sn) or
      cobalt-57 (57Co) into femoral arteries of five mature greyhounds. The diaphyseal
      cortex, stripped of periosteum and devoid of marrow, was sawn into 40 pieces (10
      transverse sections x 4 anatomical quarters/section). Relative deposition
      densities of the 113Sn microspheres in 40 pieces of cortex were found. These
      values, together with their associated masses, proved, from a statistical point
      of view, that flow rate heterogeneity was substantial in the diaphysis. In
      particular, for the diaphyseal cortex, distribution of relative deposition
      densities (flow rates) in six bones was found to be positively-skewed with a
      relative dispersion ((SD/mean) x 100) of approximately 40%.

PMID- 1992066
TI  - Effect of circumferential bands on cortical vascularity and viability.
AB  - Wire cerclage devices do not restrict cortical vascularity; however, bands,
      because they are flat and wide, have been implicated as the cause of fracture
      nonunion by disruption of cortical vascularity. This experiment evaluated the
      effect of cerclage bands on the cortical vascularity of bones that had not been
      fractured. Stainless-steel bands of four sizes (2.5, 5.0, 7.5, and 10.0 mm wide)
      and nylon bands of five sizes (2.5, 3.6, 4.8, 7.6, and 9.0 mm wide) were applied
      1 cm apart to both femoral diaphyses of four mature dogs. In two additional dogs,
      18-gauge cerclage wires were applied 5 mm apart on one femur and nylon bands were
      applied immediately adjacent to one another on the other femur to cover 3 cm of
      the length of each femoral diaphysis. These six dogs were euthanatized and
      perfused 7 days postoperatively and specimens were studied by microangiography
      and correlated histology. Two additional dogs were studied 4 and 15 weeks after
      application of nylon and metal bands. There was no evidence of complete cortical
      devascularization under any size or type of cerclage appliance at any time
      interval. Numerous examples of vessels traversing the cortex directly beneath all
      the cerclage appliances were observed. Cerclage devices, even when flat and wide,
      do not restrict cortical vascularity when applied to intact bones.

PMID- 1992067
TI  - Hemiepiphyseal reconstruction using tissue donated from fetal limbs in a murine
      model.
AB  - Epiphyseal reconstruction in the immature skeleton could have great clinical
      significance. Hemiepiphyseal reconstruction was performed in a murine model by
      transplanting fetal tissue to surgically created defects in postnatal mice.
      Reconstruction is facilitated by the existence of inbred strains. While the
      reconstruction as performed here did not completely restore the growth
      characteristics of the epiphysis, the model represents a potentially fruitful
      interface between basic and clinical biology.

PMID- 1992068
TI  - Radiographic assessment of longitudinal growth of the rabbit femoral physes.
AB  - Using surgically implanted metal markers, serial radiographs of 17 immature
      femurs were evaluated for growth of the entire femur and of the distal femoral
      physis in rabbits 20 to 100 days of age. From these data the rate of longitudinal
      growth was plotted. The most rapid growth during the study period was from 20 to
      40 days. Growth rates reached a plateau at 100 days of age. The increases in
      length for unit of time were compared for the entire femur and the distal physis.
      The distal physis was responsible for approximately 65-70% of the femoral growth
      for the study period. As an internal control of reproducibility of measurement,
      two means of determining distal femoral growth rates were compared. Their best
      fit curves proved to be almost identical. The model of evaluation of femoral
      growth is reproducible and can serve as a control against which variables in
      growth can be compared.

PMID- 1992069
TI  - [99mTc]diphosphonate uptake and hemodynamics in arthritis of the immature dog
      knee.
AB  - The relationship between [99mTc]diphosphonate uptake and bone hemodynamics was
      studied in canine carrageenan-induced juvenile chronic arthritis. Blood flow was
      determined with microspheres, plasma and red cell volumes were measured by
      labeled fibrinogen and red cells, and the microvascular volume and mean transit
      time of blood were calculated. Normal femoral epiphyses had lower central and
      higher subchondral blood flow and diphosphonate uptake values. Epiphyseal
      vascular volume was uniform, resulting in a greater transit time of blood
      centrally. In arthritis, blood flow and diphosphonate uptake were increased
      subchondrally and unaffected centrally, while epiphyseal vascular volume was
      increased throughout, leading to prolonged transit time centrally. The normal
      metaphyses had low blood flow and diphosphonate uptake values in cancellous bone
      and very high values in growth plates, but a large vascular volume throughout.
      The mean transit time therefore was low in growth plates and high in adjacent
      cancellous bone. Arthritis caused decreased blood flow and diphosphonate uptake
      in growth plates but increased vascular volume and transit time of blood.
      Diphosphonate uptake correlated positively with blood flow and plasma volume and
      negatively with red cell volume in a nonlinear fashion. Thus, changes in
      diphosphonate uptake and microvascular hemodynamics occur in both epiphyseal and
      metaphyseal bone in chronic synovitis of the immature knee. The
      [99mTc]diphosphonate bone scan seems to reflect blood flow, plasma volume, and
      red cell volume of bone.

PMID- 1992070
TI  - Necrosis of the capital femoral epiphysis and medial approaches to the hip in
      piglets.
AB  - In an attempt to produce necrosis of the femoral head, the medial femoral
      circumflex vessels were disrupted in 13 normal piglet hips through a medial
      approach. Femoral heads were recovered 3-6 months (average 4.2 months)
      postoperatively. None of these hips showed gross, radiographic, or microscopic
      evidence of necrosis. This demonstrates that necrosis, which may occur after the
      medial approach in the hip of a child, is not due to the direct damage to the
      medial femoral circumflex vessels.

PMID- 1992071
TI  - Effects of gamma irradiation on the initial mechanical and material properties of
      goat bone-patellar tendon-bone allografts.
AB  - The effects of 60Co gamma irradiation on the initial mechanical properties of the
      composite bone-patellar tendon-bone unit (CU) and the tendon midsubstance (TM)
      were studied. Frozen specimens were exposed to either 2 or 3 Mrad of gamma
      irradiation. Paired frozen specimens served as intraanimal controls. Treatment
      effects on the CU were assessed using four mechanical parameters. Effects on the
      TM were assessed using four material parameters measured using an optical surface
      strain analysis system. The maximum force and strain energy to maximum force of
      the composite unit were significantly reduced 27% and 40%, respectively, after 3
      Mrad of irradiation (p less than .05). Mechanical properties of the CU were not
      significantly altered, however, following 2 Mrad of irradiation. Based on
      individual paired contrasts between treatment and control, significant
      differences were also found in the material properties of the tendon
      midsubstance. The maximum stress, maximum strain, and strain energy density to
      maximum stress were significantly reduced following 3 Mrad, but not 2 Mrad, of
      irradiation. The results provide important "time zero" material property data,
      which will be useful for later anterior cruciate ligament reconstruction studies
      using irradiated allograft patellar tendons in the goat model and other animal
      models as well.

PMID- 1992072
TI  - A quantitative analysis of matrix alignment in ligament scars: a comparison of
      movement versus immobilization in an immature rabbit model.
AB  - This investigation quantified the alignment of fibrillar matrix in normal rabbit
      medial collateral ligaments (MCLs) and in healing MCLs from animals treated with
      or without knee immobilization. Twenty-four immature female rabbits were given
      complete midsubstance injuries to their right MCLs. Fifteen of them had that knee
      pin immobilized in flexion, while the remaining nine were allowed unrestricted
      cage activity. Animals were sacrificed in groups of three at intervals of 3, 6,
      or 14 weeks after injury, and both healing MCLs and unoperated contralateral
      controls were fixed in situ for subsequent removal, freeze-fracture, and
      preparation for scanning electron microscopy (SEM). A random sampling of SEM
      photographs followed by automated, statistically validated image processing was
      used to quantify alignment of matrix in all samples. Results showed that
      nonimmobilized MCL scars in this model do remodel over 14 weeks of healing,
      returning to normal alignment values in that time. Surprisingly, MCL scars in
      immobilized knees were even better, with mean matrix alignments falling
      statistically within normal MCL limits at all healing intervals studied. If not
      due to an unknown sampling or fixation artifact, these results suggest that gross
      knee flexion and extension is not a prerequisite for scar matrix alignment in
      this immature model of ligament healing.

PMID- 1992073
TI  - Large compressive preloads decrease lumbar motion segment flexibility.
AB  - The bending, shear, and torsion flexibilities of 13 intact adult lumbar motion
      segments (from 11 men, two women, 48-83 years of age) were compared under three
      different compressive preloads, 0, 2,200, and 4,400 N. Test forces and moments up
      to 160 N and 16 Nm were applied at the center of the upper end plate of the
      intact disc. A compressive preload of 2,200 N resulted in a significant decrease
      in motion segment flexibilities in all seven test directions (p less than 0.06)
      when compared with results obtained with no preload; the preload decreased
      flexibility 2.6, 4.5, and 6.1 times in bending, axial torsion, and shear,
      respectively. These results suggest that studies of internal trunk load-sharing
      between active and passive tissues during strenuous tasks, which engender large
      spine compressive loads, should take these changes in spine passive resistance
      into consideration.

PMID- 1992075
TI  - Variation of collagen fiber alignment in a joint surface: a scanning electron
      microscope study of the tibial plateau in dog, rabbit, and man.
AB  - To determine if articular cartilage collagen fiber organization differs with
      location on the tibial plateau, specimens from dogs, humans, and rabbits were
      studied by scanning electron microscopy. Joint surfaces were fixed, dehydrated,
      and fractured radially so that the periphery could be compared with the center on
      single specimens. Generally, fibers were more tightly packed in the lateral side
      than in the medial and the periphery as compared with the center, where the
      cartilage was consistently thicker and the radial zone was dominant and composed
      of straight vertical fibers. In the periphery, the tangential and transitional
      zones were better developed and contributed up to 50% of the cartilage depth in
      comparison to only 5% centrally. The soft, dull, malacic appearance of the center
      results from lack of a true surface layer of tangential collagen fibers.

PMID- 1992074
TI  - Anterior and posterior internal fixation of vertical shear fractures of the
      pelvis.
AB  - A laboratory study was undertaken to evaluate the effectiveness of alternative
      methods of fixation of unilateral vertical shear fractures of the pelvis. Prior
      to experimental testing, a biomechanical analysis was performed to estimate the
      forces that displace the hemipelvis in the presence of two different patterns of
      injury: an interforaminal sacral fracture and a disruption of the sacroiliac
      joint. These lesions were then experimentally created in five unembalmed human
      pelvises and sequentially fixed with an external Hoffmann frame alone, a Hoffmann
      frame with sacral bars, or sacral bars with either one or two bone plates placed
      across the symphysis pubis. Each pelvis/fixator system was mechanically tested by
      loading along the direction of the resultant muscle force predicted by the
      biomechanical analysis. During loading the proximal migration of the ilium was
      continuously recorded with a transducer. At intervals during loading, the three
      dimensional displacement of the detached hemipelvis at the pubic symphysis was
      also measured using a stereophotographic technique. With both the sacral fracture
      and the sacroiliac disruption, the addition of posterior sacral rods
      substantially increased the strength and rigidity of fixation provided by the
      Hoffmann fixation frame alone (p less than 0.01). In specimens with a sacral
      fracture, the use of anterior plates with posterior rods restored 65-71% of the
      strength of the intact pelvis, in comparison with 46% observed with the
      combination of sacral rods with an anterior Hoffmann frame (p less than 0.01).
      All of the methods of fixation evaluated in this study were less successful in
      stabilizing the sacroiliac disruption.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1992076
TI  - The effect of acute denervation on the microcirculation of skeletal muscle: rat
      cremaster model.
AB  - Although tissue is denervated during replantation of a severed part, tissue
      transfer, or muscle transplantation, there are few studies concerning the effects
      of acute denervation on muscle microcirculation. We have described a surgical
      procedure that totally denervates the rat cremaster muscle. Histological
      examination of the denervated tissue has given convincing evidence of nerve
      degeneration and skeletal muscle atrophy, accompanied by electrophysiological
      evidence of total denervation. The diameters of each component of the
      microcirculation were measured before and after denervation. Arterioles and
      arteries ranging in size from 10 to 70 microns in diameter were found to increase
      significantly in size immediately after acute denervation. Larger arteries and
      veins did not undergo significant diametrical increases. These findings suggest
      that total acute denervation significantly increases the diameter of small
      arteries and arterioles, thereby decreasing the resistance in the arterial bed
      and increasing blood flow. Since this phenomenon is of limited duration (20 min),
      it would appear to be ineffective in enhancing reperfusion and oxygenation at the
      time of reattachment of amputated parts or during vascularized tissue transfers,
      until methods of prolonging it for several hours or more are found.

PMID- 1992077
TI  - Cell association of fretting corrosion products generated in a cell culture.
AB  - The nature and distribution of corrosion products released into the body from
      orthopaedic implants remains an important issue. Various approaches to study this
      problem have been taken, such as the injection of metal salts, the injection of
      corrosion products, analysis of retrieved implants and adjacent tissue, and
      stimulated corrosion in vivo, with collection of body fluids and tissues for
      analysis. Tissue culture techniques have also been used to study the cellular
      response to metal salts or to corrosion or wear products that were generated in a
      separate environment. In this study, fretting corrosion of stainless steel plates
      and screws and of cobalt-chromium alloy plates with stainless steel screws was
      undertaken within a cell culture. The results showed that the cell cultures
      remained viable despite considerable metal ion release. Nickel was released in
      all cultures with fretting corrosion and was found mainly in the tissue culture
      medium (supernatant of the harvested cultures). Cobalt was detected only in those
      cultures with fretting corrosion of the cobalt-chromium alloy, and it was present
      mainly in the tissue culture medium. Chromium was released in all cultures with
      fretting corrosion, and it was found to be associated mainly with the cells with
      little in the culture medium. This compartmentalization of cell-associated
      chromium and fluid-associated cobalt and nickel supports in vivo studies showing
      chromium accumulation in red blood cells or tissue sites and comparatively low
      levels of nickel and cobalt.

PMID- 1992079
TI  - Applications of nuclear magnetic resonance in parasitology.
AB  - The basis of the nuclear magnetic resonance (NMR) phenomenon is described in a
      classical framework with emphasis on magnetic nuclei of 1/2 spin, including 1H,
      13C, and 31P. Biological applications of NMR spectroscopy and magnetic resonance
      imaging (MRI) are outlined briefly. NMR spectroscopic studies on parasitic
      protozoa, cestodes, nematodes, trematodes, and hymenopterous insect parasites are
      reviewed. NMR and MRI investigations on the pathophysiology of the host are also
      discussed, and the potential future of NMR applications in parasitology outlined.

PMID- 1992078
TI  - Comparison of the stability of press-fit hip prosthesis femoral stems using a
      synthetic model femur.
AB  - The motion of three different press-fit hip prosthesis femoral components was
      compared with that of a cemented stem and an Austin Moore noncemented
      hemiarthroplasty. Synthetic composite femurs were used as an experimental model
      to reduce the variations in shape and quality typical among cadaver femurs.
      Motion was measured under axial and rotational loading approximating a walking
      load. On the initial application of load, axial subsidence was as much as several
      millimeters for the noncemented stems. Considerable tightening occurred during
      the 5,000 walking cycles, such that the motion of the noncemented stems in some
      directions eventually was as small as that of the cemented stem, on the order of
      tens of microns.

PMID- 1992080
TI  - Histopathology of nymphal pentastomid infections (Sebekia mississippiensis) in
      paratenic hosts.
AB  - The histopathologic alterations occurring in mice, hamsters, turtles, and a frog
      were described following experimental infection with nymphs of Sebekia
      mississippiensis. Initially, nymphal migration caused traumatic tissue damage and
      hemorrhage characteristic of larva migrans. Subsequent inflammatory responses
      included cellular infiltration with eosinophils, macrophages, and lymphocytes,
      and fibrotic encapsulation of the nymphs. Dead nymphs were surrounded by a
      necrotic granulomatous response similar to that reported previously in humans and
      other animals. Differences were not seen in animals given single or multiple
      infections, but mice and hamsters exhibited a more marked inflammatory response
      than turtles. Overall, the histopathologic response to nymphal infections
      resembled those seen in infections resulting from ingestion of eggs, and both
      sources of infection should be considered in epidemiologic investigations of
      naturally occurring pentastomiasis.

PMID- 1992081
TI  - Plagiorchis noblei (Plagiorchiidae) in Aedes aegypti: parasite acquisition and
      host mortality in trickle infections.
AB  - The prevalence and intensity of experimental infections of Aedes aegypti with the
      digenean Plagiorchis noblei increased significantly with the level of trickle
      exposure to cercariae. Daily exposure to doses of 16 cercariae/day yielded a mean
      infection intensity of 13.0 metacercariae; doses of 1 cercaria/day resulted in
      only 2.4 metacercariae per infected mosquito larva. The prevalence of infection
      rose from 46% at an exposure of 1 cercaria/day to 99% at 16 cercariae/day. Host
      mortality rose concomitantly from 25% to 88%. Host mortality and parasite
      acquisition were independent of environmental temperatures (21-29 C), despite the
      fact that developmental times, and consequently the number of daily exposures,
      were more than 50% greater at the low end of the temperature scale. This may be
      attributable to low activity of mosquito larvae and the resulting decrease in the
      number of encounters with cercariae.

PMID- 1992082
TI  - Exposure of Dugesia tigrina (Turbellaria) to cercariae of Echinostoma trivolvis
      and Echinostoma caproni (Trematoda).
AB  - Laboratory-reared planarians, Dugesia tigrina, were exposed to cercariae of
      Echinostoma trivolvis or Echinostoma caproni. Of 100 D. tigrina exposed to 2,750
      cercariae of E. trivolvis, 29 were infected with a total of 85 encysted
      metacercariae 24 hr postinfection (PI). None of 40 D. tigrina exposed to 1,100
      cercariae of E. caproni was infected with metacercariae 24 hr PI. Cyst structure
      of E. trivolvis from the parenchyma of D. tigrina varied from normal to abnormal.
      Metacercariae removed from planarians could be excysted in an alkaline trypsin
      bile salts medium. Cercariae of E. trivolvis were not attracted to dialysate
      material from D. tigrina. Cercariae of E. trivolvis that penetrated, but did not
      encyst in planarians, voided the contents of their paraesophageal glands.
      Cercariae of E. caproni lack paraesophageal glands. Secretions of those glands
      probably are involved in tissue penetration of D. tigrina by E. trivolvis
      cercariae.

PMID- 1992083
TI  - Examination of tissue cyst formation by Toxoplasma gondii in cell cultures using
      bradyzoites, tachyzoites, and sporozoites.
AB  - Tissue cyst formation by a goat isolate (GT-1) of Toxoplasma gondii was examined
      in bovine monocyte, human fetal lung, and Madin-Darby bovine kidney cell
      cultures. Transmission electron microscopy (TEM) and cat feeding studies
      indicated that tissue cysts were present in all 3 cell lines examined. Tissue
      cysts were first seen 3 days postinoculation (PI) using TEM. Standard cell
      culture procedures were used and no additional condition was needed to induce
      tissue cyst formation. Cats fed cell cultures excreted T. gondii oocysts in their
      feces 5-7 days PI. These oocysts caused lethal infections in mice. Tissue cysts
      were produced in cell cultures regardless if the initiating inoculum consisted of
      bradyzoites, sporozoites, or a mixture of bradyzoites and tachyzoites. Tissue
      cyst formation has been followed through 40 subpassages of infected cells. By TEM
      tissue cysts still were present after 40 passages, but when 40th-passaged
      cultures were fed to cats, oocytsts were not excreted. This indicates that the
      parasite had become oocystless after repeated passage in vitro.

PMID- 1992084
TI  - Life cycles of Echinococcus multilocularis in relation to human infection.
AB  - The cycle of Echinococcus multilocularus in natural and synanthropic hosts was
      investigated during 10 yr in an endemic focus of alveolar hydatid disease in the
      Massif Central of France. The natural cycle, involving red foxes, Vulpes vulpes,
      and voles, Arvicola terrestris, existed immediately surrounding a village in
      which human cases of alveolar hydatid disease occurred. Both foxes and free
      ranging dogs could serve as the source of infection for the human population.

PMID- 1992085
TI  - In vitro effects of fetal bovine serum and glucose on multiplication of Cryptobia
      salmositica.
AB  - Cryptobia salmositica multiplied rapidly at 10 C in a minimum essential medium
      (containing 1.0 mg glucose/ml, Hanks' salts and L-glutamine) supplemented with
      heat-inactivated fetal bovine serum (FBS) and HEPES buffer (25 mM). The
      multiplication rate of C. salmositica was related to the amount of FBS; the peak
      number (approximately 9 x 10(6) parasites/ml) was attained in about 6 wk when the
      medium contained 25% final concentration of FBS. Glucose utilization was related
      to the number of parasites; the maximum utilization was reached before peak
      numbers. Formation of rosette colonies was correlated with multiplication rate
      and numbers of parasites in cultures. Degenerate round forms found in old
      cultures probably were caused by the accumulation of metabolic wastes in the
      medium.

PMID- 1992086
TI  - Localization of lectin-binding sites and sugar-binding proteins in tachyzoites of
      Toxoplasma gondii.
AB  - Lectins and neoglycoproteins labeled with colloidal gold particles were used for
      the ultrastructural localization of carbohydrate residues and sugar-binding
      sites, respectively, in thin sections of tachyzoites of Toxoplasma gondii
      embedded in the Lowicryl K4M resin. Incubation of the sections in the presence of
      gold-labeled Canavalia ensiformis (Con A), Arachis hypogaea (PNA), Ricinus
      communis I (RCA I), Triticum vulgaris (WGA), and Limax flavus (LFA) agglutinins
      showed significant labeling of the rhoptries. However, no labeling of the
      parasite's surface was observed. Incubation of tachyzoites in the presence of
      gold-labeled albumin-N-acetyl-D-glucosamine or albumin-galactose, but not in the
      presence of albumin-mannose, led to labeling of the rhoptries in a pattern
      similar to that observed with the lectins. The results obtained are discussed in
      relation to the possible role played by secretion of rhoptry macromolecules
      during the process of T. gondii-host cell interaction.

PMID- 1992087
TI  - Ivermectin inhibits molting of Wuchereria bancrofti third stage larvae in vitro.
AB  - The effect of ivermectin or diethylcarbamazine (DEC) on Wuchereria bancrofti
      molting from the third to the fourth larval stage (L3 to L4) was evaluated in
      vitro. L3 larvae were harvested from laboratory-reared Aedes togoi 2 wk after
      feeding upon a microfilaremic human volunteer. The larvae were kept in an
      artificial medium (Franke's NI medium) with 10% human serum under an atmosphere
      of 5% CO2 for 20 days. Experimental tubes also contained ivermectin (0.1-1,000
      ng/ml) or DEC (0.1-10,000 ng/ml). An estimated concentration of 50 ng/ml
      ivermectin inhibited molting in 50% of the larvae expected to molt. For DEC, this
      value was roughly 1,000 ng/ml. In this in vitro culture system, ivermectin
      inhibited the L3 to L4 molt of W. bancrofti and was roughly 20-fold more potent
      in this activity than DEC.

PMID- 1992088
TI  - Tissue alterations in Microtus montanus chronically infected with Trypanosoma
      brucei gambiense.
AB  - Changes in liver, spleen, kidneys, heart, and brain are reported for Microtus
      montanus chronically infected with Trypanosoma brucei gambiense. An increase in
      body weight of infected animals was attributable to a significant increase in
      total mass of spleen, liver and kidney. Cellular infiltrate consisting primarily
      of lymphocytes and plasma cells was observed in all organs and was particularly
      evident in intralobular connective tissue of the liver, adipose tissue of the
      hilum, and adjacent medullary region of the kidney, spleen, and the meninges.
      Disruption of normal metabolism and the pathological changes observed in liver
      and kidney suggest that the survival of trypanosome-infected voles is dependent
      largely on the physiological response occurring in these organs.

PMID- 1992089
TI  - Factors V and VII anticoagulant activities in the salivary glands of feeding
      Dermacentor andersoni ticks.
AB  - The salivary glands of Dermacentor andersoni ticks possess anticoagulant
      activities that can alter the clotting time of rabbit whole blood. Salivary gland
      extracts from female ticks inhibit both the intrinsic and extrinsic coagulation
      systems, and maximal activities against both pathways occur when the ticks attain
      about 250 mg feeding weight. These anticoagulants are directed against both
      coagulation factors V and VII, but they do not affect factors II or X. Despite
      this salivary anticoagulant activity, heavily tick-infested rabbits suffer no
      visible alteration of their peripheral blood coagulability and have no detectable
      circulating fibrin degradation products, suggesting that the ticks do not secrete
      a factor with fibrinolytic activity.

PMID- 1992090
TI  - Cryptosporidium parvum infection in mice: inability of lymphoid cells or culture
      supernatants to transfer protection from resistant adults to susceptible infants.
AB  - The ability of murine lymphoid cells or culture supernatant fractions to transfer
      protection against Cryptosporidium parvum was examined. Spleen or mesenteric
      lymph node (MLN) cells were taken from adult mice resistant to C. parvum and
      given either directly or following in vitro culture to infant mice. Neither
      spleen or MLN cells, nor cells or supernatant fractions from in vitro cultures
      transferred protection from resistant adult donors to susceptible infant
      recipients. These results may be due to limitations in the present model.
      Alternatively, the resistance of infant mice to C. parvum may not be
      immunologically mediated.

PMID- 1992091
TI  - Brugia pahangi in rats: increasing the number of infective larvae inoculated
      increases the percentage of microfilaremic rats.
AB  - One hundred Brugia pahangi infective larvae (L3) caused microfilaremic (mf + ve)
      infection in 56% of inbred PVG rats. Adult worms were recovered consistently from
      infected rats but worm recovery was very low, only 1-3% of L3 inoculated survived
      to adulthood and the worms were dispersed in a wide range of anatomical sites.
      This suggested that lack of microfilaremia may be due to the low probability of
      male and female worms meeting in the same site and thus may be numerically and
      topographically based. When the number of infective larvae inoculated was
      increased to 500, the percentage of mf + ve infections in rats also increased to
      94%, corroborating the hypothesis that lack of mf was not due to an immune
      response. In a further experiment all infected rats had lost both mf and adult
      worms by day 420. It has yet to be established whether final rejection of the
      parasite is due to immunity.

PMID- 1992092
TI  - The description of Paralongicollum nemacheili n. gen., n. sp. (Acanthocephala:
      Pomphorhynchidae) from freshwater fishes in Kazakh S.S.R.
AB  - Paralongicollum nemacheili n. gen., n. sp. is described from Salmo gairdneri
      Richardson and Nemacheilus stoliczkai Steindacher in Lake Kul'say in the basin of
      Lake Balkhash, Kazakh S.S.R. Its long uniformly cylindrical neck and nonfiliform
      proboscis distinguish it from the other 3 genera of the family. Tenuiproboscis
      Yamaguti, 1935, has a filiform proboscis. The neck of Pomphorhynchus Monticelli,
      1905, has a bulb anteriorly, and that of Longicollum Yamaguti, 1935, is spirally
      twisted with expansions. A key to the genera of Pomphorhynchidae is provided. The
      relatively longer necks in juveniles than in larger worms probably enhance the
      establishment of new infections. A large proportion of worms had extensive body
      wall deformities. Longicollum sergenti (Choquette and Gayot, 1952) Golvan, 1969,
      is relegated to the new genus Paralongicollum.

PMID- 1992093
TI  - Blood parasites of some birds from northeastern Mexico.
AB  - A total of 196 birds of 31 species from 15 families from northeastern Mexico was
      examined for blood parasites; 25 birds (12.8%) of 11 species harbored 1 or more
      species of hematozoans. Species of Haemoproteus accounted for half of the total
      infections encountered. Leucocytozoon simondi was found in 2 Mexico ducks (Anas
      diazi) and this represents the first record of the transmission of this parasite
      in Mexico. The results of this survey were compared with those obtained nearly 50
      yr ago from a survey of birds from the same general area; prevalence in both
      samples was similar, despite the change to a more agricultural environment over
      this period.

PMID- 1992094
TI  - Heliconema brooksi n. sp. (Nematoda: Physalopteridae) from the ophichthid eel
      Ophichthus gomesi in the Gulf of Mexico.
AB  - Heliconema brooksi n. sp. is described from the shrimp eel, Ophichthus gomesi, in
      Mississippi Sound. This species is distinguished from other members of the genus
      by possessing in the male 40 or more tessellated longitudinal ridges, a spicule
      ratio averaging 1:10.6, 4 precloacal papillae, and 6 postcloacal papillae.
      Females have a protruding vulvular flap. Both sexes have a prominent sclerotized
      cardium. Heliconema brooksi is morphologically most closely related to Heliconema
      heliconema. A juvenile worm from the white shrimp, Penaeus setiferus, in the same
      locality may be the infective stage.

PMID- 1992095
TI  - Salsuginus yutanensis n. sp. (Monogenea: Ancyrocephalidae) from Fundulus
      sciadicus in Clear Creek of eastern Nebraska.
AB  - Salsuginus yutanensis n. sp. (Monogenea: Ancyrocephalidae) is described from the
      gills of the plains topminnow, Fundulus sciadicus Cope, from Clear Creek in
      eastern Nebraska. Salsuginus yutanensis is distinguished from previously
      described species by having a shorter accessory piece and different hamulus
      proportions, especially in the relative lengths of deep and superficial roots. In
      addition, the angles between deep and superficial roots distinguish S. yutanensis
      from several congeners.

PMID- 1992096
TI  - Prevalence and isolation of Toxoplasma gondii from white-tailed deer in Alabama.
AB  - Nineteen white-tailed deer (Odocoileus virginianus) from 5 counties in Alabama
      were examined for infection with Toxoplasma gondii. Twenty-gram samples of heart
      tissue were bioassayed in mice, serum was examined for T. gondii antibodies using
      the direct agglutination test, and sections of heart muscle were examined
      histologically for tissue cysts. Toxoplasma gondii was isolated from 4 of 19
      (21%) white-tailed deer hearts. Antibody titers of greater than or equal to 1:50
      were found in sera from 7 of 16 (44%) white-tailed deer. Histological
      examinations of tissue sections from white-tailed deer hearts were negative for
      T. gondii.

PMID- 1992097
TI  - Redescription of Trichuris tenuis Chandler, 1930, from llamas (Lama glama) in
      Oregon with a key to the species of Trichuris present in North American
      ruminants.
AB  - Whipworms collected from llamas (Lama glama) in Oregon were identified as
      Trichuris tenuis Chandler, 1930. A redescription, based on the specimens
      collected from llamas and examination of the paratypes, is presented. The unique
      form of the cloaca in T. tenuis separates males of this species from all other
      species of Trichuris known to occur in ruminants. Among species of Trichuris for
      which adequate descriptions of the female exist, T. tenuis can be distinguished
      using an array of characters including an uneverted, aspinous vulva and a highly
      convoluted vagina with papillalike spines in the proximal one-fourth and a small
      egg chamber located approximately midway along its length. This constitutes only
      the second report of T. tenuis in North America and brings to 7 the number of
      species of Trichuris known to occur in sylvatic and domestic ruminants in North
      America.

PMID- 1992098
TI  - A dot-ELISA mimicry western blot test for the detection of swine trichinellosis.
AB  - A dot enzyme-linked immunosorbent assay (dot-ELISA) using antigens purified by
      monoclonal antibody affinity chromatography was developed for detecting
      Trichinella spiralis infection in swine. The test was as sensitive as an ELISA
      using excretory-secretory products as antigen and western blot analysis, and
      nearly as specific as the western blot. The dot-ELISA detected all of 20 low
      infections (0.08-4.74 larvae per gram of diaphragm), most of them by 5-6 wk
      postinfection. Sera from 1,960 farm-reared swine were tested by conventional
      ELISA, dot-ELISA, and western blot. Of the 1,960 sera, 262 (13.4%) were
      considered positive on conventional ELISA, 16 (0.82%) by dot-ELISA, and 15
      (0.77%) by western blot. The improved specificity was achieved by employing
      species-specific denatured antigens. More importantly, the dot-ELISA was much
      simpler to perform than western blot analysis. The principles employed in this
      test can be adapted to other infectious diseases, such as AIDS.

PMID- 1992099
TI  - Utility of a Haemonchus contortus/jird (Meriones unguiculatus) model for studying
      resistance to levamisole.
AB  - Trichostrongylid nematodes of sheep commonly are identified as exhibiting
      resistance to levamisole. In vitro assays have been developed to study levamisole
      resistance for Haemonchus contortus, but no in vivo model has been identified for
      this species. To determine the utility of a H. contortus/jird (Meriones
      unguiculatus) model for examining levamisole resistance, immunosuppressed jirds
      were inoculated with approximately 1,000 exsheathed infective larvae of H.
      contortus (resistant or susceptible to levamisole), treated per os on day 10
      postinoculation (PI) with levamisole hydrochloride or analogs of the drug, and
      killed on day 13 PI. Stomachs were removed, opened longitudinally, incubated in
      distilled water at 37 C for 5 hr, fixed in formaldehyde solution, and stored for
      subsequent microscopic examination. Doses of levamisole and its analogs, which
      elicited percentage clearances of greater than or equal to 93.5 for the
      susceptible strain, cleared less than or equal to 68.9% of the resistant worms.
      These data are consistent with activities for the drugs against wild-type and
      levamisole-resistant strains of Caenorhabditis elegans. Thus, the H.
      contortus/jird model provides a useful in vivo tool to study resistance to
      levamisole and possibly other anthelmintics.

PMID- 1992100
TI  - Blood vessels in Trichinella spiralis infections: a study using vascular casts.
AB  - Larvae of Trichinella spiralis initiate the transformation of myocytes into nurse
      cells that become surrounded by elaborate networks of blood vessels. To examine
      the structure of these networks (i.e., retes), transcardic perfusion was used to
      clear the vascular tree of Trichinella-infected mice and to inject a plastic that
      polymerized in situ. Vascular complexes were found only around infected myocytes
      and were characterized by large circumferential vessels that give rise to the
      smaller channels of the retes. The secondary vessels vary widely in caliber and
      are distributed in a random fashion. Three types of network were found: simple,
      complex, and hypercomplex, and they were distributed normally, with the complex
      retes the most common. Comparison of the structure of the baskets with that of
      vessels in surrounding uninfected muscle strongly suggests that the vascular
      retes are the result of de novo angiogenesis induced during the infection. The
      parasite may elicit angiogenesis directly through secretion of unique products or
      may elicit a change in the nurse cell that, in turn, results in growth of new
      blood vessels.

PMID- 1992101
TI  - Marked elevations of serum alkaline phosphatase in patients with AIDS.
AB  - We have observed many patients with AIDS who have unexplained marked elevations
      in serum alkaline phosphatase. To determine the frequency of alkaline phosphatase
      elevations in patients with AIDS, and to identify diagnoses, medications, and
      demographic factors associated with such elevations, we conducted a retrospective
      study of the first 90 consecutive AIDS cases in hospitals affiliated with the
      University of Colorado Health Sciences Center in Denver, Colorado. We found
      elevations of alkaline phosphatase in excess of 1,000 IU/L in 17% of consecutive
      patients with AIDS. This level of elevation was less frequent in patients with
      Kaposi's sarcoma but there was otherwise no significant association with
      diagnoses or medications, or transmission categories for AIDS. The majority of
      the patients with elevations to this level did not have documented opportunistic
      infections or biliary tract dilatation previously described in the "cholangitis"
      syndrome in AIDS patients. Other explanations for these elevations for this
      common laboratory finding may exist.

PMID- 1992102
TI  - Dapsone as a single agent is suboptimal therapy for Pneumocystis carinii
      pneumonia.
AB  - In a prospective, noncomparative study, seven patients with mild Pneumocystis
      carinii pneumonia, characterized by room air arterial PO2 greater than 60 mm Hg
      at the time of presentation, were treated with dapsone alone at a dose of 200 mg
      daily. Two of the seven patients required mechanical ventilation for respiratory
      failure on day 5 of dapsone therapy; both died. Four patients experienced major
      side effects during dapsone therapy. None of the seven patients successfully
      completed a full course of therapy with dapsone. We conclude that high-dose,
      single-agent dapsone is not suitable for further study as therapy for
      Pneumocystis carinii pneumonia.

PMID- 1992103
TI  - MRI-guided stereotaxic brain biopsy in neurologically symptomatic AIDS patients.
AB  - Two patients with AIDS-related neurologic dysfunction were evaluated with both
      computed tomographic (CT) brain scans and magnetic resonance imaging (MRI). CT
      scans were essentially normal in both patients while MRI revealed focal lesions
      amenable to brain biopsy. Using newly developed instrumentation, MRI-guided
      stereotaxic brain biopsy was performed without complication. The benefits and
      impact of this new technology for the care of neurologically symptomatic AIDS
      patients is discussed.

PMID- 1992104
TI  - A multicenter proficiency trial of gene amplification (PCR) for the detection of
      HIV-1.
AB  - The sensitivity and specificity of the polymerase chain reaction (PCR) for the
      detection of HIV-1 proviral DNA was determined in five laboratories with
      extensive experience in PCR testing. Five panels consisting of 105 HIV-1
      seronegative specimens from regularly repeating blood donors with no risk factors
      for HIV infection and 99 HIV-1-seropositive and culture-positive specimens from a
      cohort of homosexual/bisexual men were sent under code to each laboratory.
      Amplification procedures and testing algorithms by which specimens were judged
      positive, negative, or indeterminate varied between laboratories. The average
      sensitivity for the five laboratories was 99.0%, with two laboratories achieving
      100%. The average specificity was 94.7%, varying between 90.5 and 100%. The
      overall false-positive rate was 1.8%, the false-negative rate was 0.8%, and the
      indeterminate rate was 1.9%. Of 1,005 determinations made by the five
      laboratories, 32 (3.2%) were misclassifications. Most of the classification
      errors occurred in specimens from uninfected individuals and were distributed
      among the laboratories in such a way as to indicate laboratory error rather than
      the inherent reactivity of some samples. This emphasizes the need for
      standardization of PCR testing and caution in interpreting positive PCR reactions
      in HIV-1-seronegative persons.

PMID- 1992105
TI  - HTLV-I-associated leukemia/lymphoma in south Florida.
AB  - We report here 10 cases of adult T-cell leukemia/lymphoma (ATL) seen in South
      Florida between February 1988 and July 1989. All were seropositive for human T
      lymphotropic virus type I (HTLV-I) and seronegative for human immunodeficiency
      virus type 1 (HIV-1). DNA extracted from tumor biopsies/peripheral blood
      lymphocytes of nine patients was shown by the polymerase chain reaction (PCR) to
      contain HTLV-I proviral DNA. Blot hybridization of DNA extracted from seven
      patients with an HTLV-I cDNA probe revealed a monoclonal pattern of proviral
      integration consistent with a diagnosis of ATL. Eight of the 10 patients were
      women. Six patients were from Haiti, three from Jamaica, and one from the
      Bahamas. All patients had very aggressive non-Hodgkin's lymphoma. Two patients
      presented with sinus and retro-orbital involvement; another had gastric lymphoma
      that perforated. Nine patients developed hypercalcemia. Eight patients died
      within 1 year of diagnosis. Two were lost to follow-up. During the course of this
      study, 66 new cases of non-Hodgkin's lymphoma were diagnosed at this hospital.
      Ten of these cases were ATL. The prevalence of HTLV-I-related lymphoma in this
      sample was 15%. Since tissue from all patients was not available for HTLV-I
      screening, however, it is possible that other cases of ATL went undetected. We
      conclude from this initial survey that a retroviral etiology should be considered
      in patients from populations known to be at risk for HTLV-I infection who present
      with non-Hodgkin's lymphoma.

PMID- 1992107
TI  - HTLV-I coninfection in a HIV-1-infected Peruvian population.

PMID- 1992106
TI  - A cross-sectional study of a program for HIV infection control among public house
      workers.
AB  - We report results of a cross-sectional study of a program for human
      immunodeficiency virus (HIV) infection control among public house workers in Dar
      es Salaam. Forty percent of the 605 workers sampled had been part of this
      program, which included behavioral counseling and provision of condoms, for 1
      year. The remaining 60% were new recruits. Program participation was associated
      with both enhanced condom use (p less than 0.001) and behavioral modification (p
      less than 0.001). Females, and specifically barmaids, were more likely to be
      condom users but were less likely to have changed their behavior in other
      respects. Seropositivity to both HIV and Treponema pallidum tended to be higher
      among females, especially the barmaids. Since barmaids and waitresses in public
      houses in Dar es Salaam often engage in prostitution, it is felt that to effect a
      reduction of numbers of their sexual partners, there is a need to address the
      social and economic factors underlying high-risk sexual behavior.

PMID- 1992108
TI  - Condom use among transvestites in Italy.

PMID- 1992109
TI  - HIV disease: pathogenesis and therapy. A symposium. Grenelefe, Florida, March 13
      17, 1991. Abstracts.

PMID- 1992110
TI  - Synthesis and antiarrhythmic activity of cis-2,6-dimethyl-alpha,alpha-diaryl-1
      piperidinebutanols.
AB  - A series of alpha,alpha-diaryl-1-piperidinebutanols was evaluated for
      antiarrhythmic activity in the coronary ligated dog model. Structure-activity
      relationship studies indicated that the 2,6-dimethylpiperidine group yielded
      compounds with the best antiarrhythmic profiles in this series. The length of the
      methylene chain separating the diarylcarbinol and the amino group was not
      crucial. Substitution of a hydrogen or a number of functional groups for the
      hydroxyl group had little effect on efficacy or duration but yielded compounds
      that produced severe tachycardias. Replacement of one of the aryl groups by
      hydrogen or a pyridinyl or cyclohexyl group had little effect on efficacy but
      decreased the duration of action. Compound 18 (pirmenol) was ultimately chosen
      for further studies and is now being investigated in man.

PMID- 1992111
TI  - Three-dimensional structure-activity relationships and receptor mapping of N1
      substituents of quinolone antibacterials.
AB  - Quantitative structure-activity relationships for quinolone antibacterials have
      been previously examined and a steric parameter L for the N1-substituents found
      to be important in QSAR equations. But some compounds for which previous QSAR
      equations could not predict the activity have appeared recently. In this study,
      conformations of a variety of N1-substituents of quinolone antibacterials were
      analyzed by a molecular modeling method. An active conformation of each of the
      compounds was estimated with information of the energy profile calculated by
      molecular orbital methods and of its biological activity. A model of a receptor
      corresponding to the N1-substituents was constructed by superposing van der Waals
      volumes of active conformer of highly active compounds. As a result of these
      conformational analyses and receptor mapping, it is proposed that there are two
      different optimum volumes for increasing the activity of quinolone antibacterials
      and two unfavorable regions for reducing the activity. It is suggested that the
      steric parameter L which appeared in previous QSAR equations corresponds to one
      of the optimum volumes of the proposed receptor model. With this receptor model,
      a relation between structure and activity of the compounds, including those
      mispredicted compounds in previous QSAR equations is able to be rationalized
      qualitatively and elegantly. We believe that this receptor model is useful for a
      prediction of the activity of compounds not yet synthesized as well as for
      designing new quinolone antibacterials.

PMID- 1992112
TI  - Novel 5-HT3 antagonists. Indole oxadiazoles.
AB  - The synthesis and biochemical evaluation of a series of indole oxadiazole 5-HT3
      antagonists are described. The key pharmacophoric elements have been defined as a
      basic nitrogen, a linking group capable of H-bonding interactions, and an
      aromatic moiety. The steric limitations of the aromatic binding site have been
      determined by substitution about the indole ring. Variation of the heterocyclic
      linking group has shown that while two hydrogen-bonding interactions are
      possible, only one is essential for high affinity. The environment of the basic
      nitrogen has been investigated and shown to be optimal when constrained within an
      azabicyclic system. These results have been incorporated into a proposed binding
      model for the 5-HT3 antagonist binding site, in which the optimum distance
      between the aromatic binding site and the basic amine is 8.4-8.9 A and the steric
      limitations are defined by van der Waals difference mapping.

PMID- 1992113
TI  - 1,2,4-Triazolo[4,3-a]pyrazine derivatives with human renin inhibitory activity.
      3.1 Synthesis and biological properties of aminodeoxystatine and difluorostatone
      derivatives.
AB  - Two series of 1,2,4-triazolo[4,3-a]pyrazine derivatives with human renin
      inhibitory activity have been synthesized which incorporate the transition-state
      mimetics (3S,4S)- and (3R,4S)-5-cyclohexyl-3,4-diaminopentanoic acid ((S)- and
      (R)-CDAPA), and (4S)-4-amino-5-cyclohexyl-2,2-difluoro-3-oxopentanoic acid
      (ACDFOPA). Several compounds in these series, for example 13a, 19c, and 19f, were
      highly potent inhibitors of partially purified human renin (IC50 values of 3.9,
      1.6, and 1.4 nM, respectively). The ACDFOPA-based compounds 19c and 19f contain
      no natural amino acid fragments and have molecular weights which compare well
      with those of previously reported inhibitors of nanomolar in vitro potency. When
      administered intravenously to anesthetized, sodium-depleted marmosets at doses of
      3 mg/kg, compounds 13a and 19c caused a marked reduction in mean arterial
      pressure, but in the same animal model at 30 mg/kg, oral activity was not seen.

PMID- 1992115
TI  - Long-acting dihydropyridine calcium antagonists. 6. Structure-activity
      relationships around 4-(2,3-dichlorophenyl)-3-(ethoxycarbonyl)-2-[(2
      hydroxyethoxy)methyl]-5 -(methoxycarbonyl)-6-methyl-1,4-dihydropyridine.
AB  - The preparation of 4-(2,3-dichlorophenyl)-3-(ethoxycarbonyl)-2-[(2
      hydroxyethoxy)methyl]-5- (methoxycarbonyl)-6-methyl-1,4-dihydropyridine (2) is
      described, and its potent calcium antagonist activity on rat aorta (IC50 = 4 x
      10(-9) M) and marked tissue selectivity in vitro for vascular smooth muscle over
      cardiac smooth muscle are established. In order to exploit the excellent in vitro
      profile of compound 2, a range of analogues were prepared but none were found to
      have superior calcium antagonist potency and tissue selectivity. Compound 2 has
      excellent in vivo activity in the anesthetized dog (ED50 = 12 micrograms/kg for
      reduction of CVR) and a plasma half-life in the conscious dog of 7.2 h. The
      pharmacokinetic parameters of 2 are compared to those determined for the
      structurally related compounds amlodipine and felodipine. The plasma clearance
      for 2 (9.6 mL/min/kg) is similar to that of amlodipine and is consistent with the
      extended 2-substituent hindering approach to the cytochrome P-450 enzyme
      responsible for oxidation of the DHP ring to the corresponding pyridine.

PMID- 1992114
TI  - Synthesis and biological evaluation of dipeptidyl and tripeptidyl polyoxin and
      nikkomycin analogues as anticandidal prodrugs.
AB  - Nine analogues (1-5, 9-12) of the peptidyl nucleoside antibiotics nikkomycin and
      polyoxin were synthesized and tested for their biological properties against
      different strains of the pathogenic yeast Candida albicans. The tripeptidyl
      series of analogues (1-5) was designed to behave as prodrugs, releasing a toxic
      moiety upon enzymatic hydrolysis inside the cell. The dipeptidyl series (9-12)
      was designed as double-targeted drugs, being themselves toxic and releasing a
      toxic amino acid upon hydrolysis. All the analogues were prepared by coupling
      suitably protected amino acid p-nitrophenyl esters to 1-(5'-amino-5'-deoxy-alpha
      D-allofuranuronosyl)uracil (UPOC) or the corresponding polyoxins and nikkomycins,
      with subsequent removal of the protecting group. Improved coupling yields were
      observed when DMSO was used as the solvent. Products were purified with use of
      reversed-phase HPLC and, in one case, diastereomeric products (compound 11) were
      resolved by using this procedure. One of the tripeptidyl nikkomycins behaved as a
      prodrug but none of the compounds, as measured by in vitro testing, proved more
      effective than nikkomycin as an anticandidal agent.

PMID- 1992116
TI  - Aldophosphamide acetal diacetate and structural analogues: synthesis and
      cytotoxicity studies.
AB  - The synthesis of aldophosphamide acetal diacetate and a number of structural
      analogues is described. These compounds are designed to undergo biotransformation
      to the corresponding aldehydes in the presence of carboxylate esterases, enzymes
      that are ubiquitous in mammalian tissue. Several of these aldehydes can
      theoretically exist in pseudoequilibrium with the 4-hydroxyoxazaphosphorine
      tautomers; others lack this capability. The half-lives of the acetals in 0.05 M
      phosphate buffer, pH 7.4, at 37 degrees C ranged from 1 to 2 days. In the
      presence of 2 unit equiv of porcine liver carboxylate esterase, all of the
      compounds were hydrolyzed with half-lives of less than 1 min. Although closely
      structurally related, the compounds exhibited a wide range of cytotoxicities to
      L1210 murine leukemia cells in vitro.

PMID- 1992117
TI  - An editor's commentary on the birth of a journal.

PMID- 1992118
TI  - Analogues of methotrexate and aminopterin with gamma-methylene and gamma-cyano
      substitution of the glutamate side chain: synthesis and in vitro biological
      activity.
AB  - Analogues of methotrexate (MTX) and aminopterin (AMT) modified at the gamma
      position of the glutamate side chain were synthesized and evaluated as
      dihydrofolate reductase (DHFR) inhibitors and tumor cell growth inhibitors.
      Condesations of 4-amino-4-deoxy-N10-methylpteroic acid (mAPA) with dimethyl DL-4
      methyleneglutamate in the presence of diethyl phosphorocyanidate (DEPC) followed
      by alkaline hydrolysis yielded N-(4-amino-4-deoxy-N10-methylpteroyl)-DL-4
      methyleneglutamic acid (gamma-methyleneMTX). Condensation of 4-amino-4-deoxy-N10
      formylpteroic acid (fAPA) with dimethyl-DL-4-methyleneglutamate by the mixed
      carboxylic-carbonic anhydride method yielded N-4-amino-4-deoxypteroyl)-DL-4
      methyleneglutamic acid (gamma-methyleneAMT). Also prepared via DEPC coupling was
      a mixture of the four possible diastereomers of N-(4-amino-4-deoxy-N10
      methylpteroyl)-4-cyanoglutamic acid (gamma-cyanoMTX). The requisite intermediate
      gamma-tert-butyl alpha-methyl 4-cyanoglutamate, as a DL-threo/DL-erythro mixture,
      was prepared from methyl N alpha-Boc-O-tosyl-L-serinate by reaction with sodium
      tert-butyl cyanoacetate followed by mild trifluoroacetic treatment to selectively
      remove the Boc group. The gamma-methylene derivatives of MTX and AMT are
      attractive because of their potential to act as Michael acceptors within the DHFR
      active site. gamma-CyanoMTX may be viewed as a congener of the nonpolyglutamated
      MTX analogue gamma-fluoroMTX. In vitro bioassay data for the gamma-methylene and
      gamma-cyano compounds support the idea that the active site of DHFR, already
      known for its ability to tolerate modification of the gamma-carboxyl group of MTX
      and AMT, can likewise accommodate substitution on the gamma-carbon itself.

PMID- 1992119
TI  - Synthesis of two cyclopentenyl-3-deazapyrimidine carbocyclic nucleosides related
      to cytidine and uridine.
AB  - The cytosine analogue of neplanocin A, cyclopentenylcytosine (CPE-C, 3), has
      significant antitumor and antiviral activity commensurate with the drug's ability
      to produce a significant depletion of cytidine triphosphate (CTP) levels that
      result from the potent inhibition of cytidine triphosphate synthetase. Another
      important antitumor agent, previously identified as a potent inhibitor of the
      same enzyme, is 3-deazauridine (2). The synthesis of the cyclopentenyl
      nucleosides 3-deaza-CPE-C (5) and 3-deaza-CPE-U (6) was undertaken in order to
      investigate the effects of a modified 3-deaza pyrimidine aglycon moiety on the
      biological activity of the parent CPE-C. These compounds were synthesized via an
      SN2 displacement reaction on cyclopenten-1-ol methanesulfonate (10) by the sodium
      salt of the corresponding aglycon. In each case, separation and characterization
      of the corresponding N- and O-alkylated products was necessary before final
      removal of the blocking groups. The target compounds were devoid of in vitro
      antiviral activity against the HSV-1 and human influenza viruses. Although 3
      deaza-CPE-C was nontoxic to L1210 cells in culture, 3-deaza-CPE-U displayed
      significant cytotoxicity against murine L1210 leukemia in vitro.

PMID- 1992120
TI  - Potential antitumor agents. 61. Structure-activity relationships for in vivo
      colon 38 activity among disubstituted 9-oxo-9H-xanthene-4-acetic acids.
AB  - Analogues of 9-oxo-9H-xanthene-4-acetic acid (XAA) bearing small, lipophilic 5
      substituents are among the most dose-potent compounds yet reported with the
      capability of causing hemorrhagic necrosis of implanted colon 38 tumors in mice.
      To further extend structure-activity relationships among this class of compound,
      a series of XAA derivatives bearing two small lipophilic groups at various
      positions have been prepared and evaluated. The 5,6-disubstituted compounds in
      particular show consistently high levels of both dose potency and activity,
      suggesting this is the optimal configuration among substituted 9-oxo-9H-xanthene
      4-acetic acids. The 5,6- dimethyl and 5-methyl-6-methoxy are the most effective
      analogues, showing in vivo colon 38 activity comparable to that of FAA at 10-15
      fold lower doses and superior activity to FAA at the respective optimal doses,
      and the former has been selected for detailed evaluation.

PMID- 1992121
TI  - Folate analogues. 34. Synthesis and antitumor activity of non-polyglutamylatable
      inhibitors of dihydrofolate reductase.
AB  - Five analogues of methotrextate (MTX), 10-deazaaminopterin (10-DAM), and 10-ethyl
      10-deazaaminopterin (10-EDAM) in which the glutamate moiety was replaced by
      either a gamma-methyleneglutamate or beta-hydroxyglutamate were synthesized and
      evaluated for their antifolate activity. These analogous are 4-amino-4-deoxy-N10
      methylpteroyl-beta-hydroxyglutamic acid (1), 4-amino-4-deoxy-10-deazapteroyl-beta
      hydroxyglutamic acid (2), 4-amino-4-deoxy-N10-methylpteroyl-gamma
      methyleneglutamic acid (3, MMTX), 4-amino-4-deoxy-10-deazapteroyl-gamma
      methyleneglutamic acid (4, MDAM), and 4-amino-4-deoxy-10-ethyl-10-deazapteroyl
      gamma-methyleneglutamic acid (5, MEDAM). None of these compounds were metabolized
      to the respective polyglutamate derivative as judged by their inability to serve
      as substrates for CCRF-CEM human leukemia cell folylpolyglutamate synthetase
      (FPGS) in vitro. All compounds inhibited recombinant human-dihydrofolate
      reductase (DHFR) at nearly equivalent magnitude as MTX. Growth-inhibition studies
      with H35 hepatoma, Manca human lymphoma, and CCRF-CEM human leukemia cells
      established greater cytotoxic effects with compounds 3-5 than with compounds 1
      and 2. gamma-Methyleneglutamate derivatives 3-5 were transported to H35 hepatoma
      cells better than MTX or beta-hydroxyglutamate derivatives 1 and 2. Compound 3
      was 2.5 times better than MTX in competing with folinic acid transport in H35
      hepatoma cells. Compound 1 did not have a significant inhibitory effect on
      folinic acid transport even at 50 microM under identical conditions. The IC50 for
      compound 1 against H35-hepatoma cell growth was 8.5-fold higher than MTX.
      Compounds with the gamma-methyleneglutamate moiety (3-5) exhibited almost equal
      or lower IC50 values than MTX against the growth of CCRF-CEM human leukemia
      cells. These studies show that on continuous exposure, the non-polyglutamylatable
      inhibitors DHFR (3-5) can exhibit superior antifolate activity compared to the
      polyglutamylatable methotrexate, presumably due to their enhanced transport to
      these cell lines. Compounds 3-5 appear to be excellent models to study the role
      of polyglutamylation of antifolates in antitumor activity and host toxicity.

PMID- 1992122
TI  - Synthesis and biological activity of the 2-desamino and 2-desamino-2-methyl
      analogues of aminopterin and methotrexate.
AB  - The previously undescribed 2-desamino and 2-desamino-2-methyl analogues of
      aminopterin (AMT) and methotrexate (MTX) were synthesized from 2-amino-5
      (chloromethyl)pyrazine-3-carbonitrile. The AMT analogues were obtained via a
      three-step sequence consisting of condensation with di-tert-butyl N-(4
      aminobenzoyl)-L-glutamate, heating with formamidine or acetamidine acetate, and
      mild acidolysis with trifluoroacetic acid. The MTX analogues were prepared
      similarly, except that 2-amino-5-(chloromethyl)pyrazine-3-carbonitrile was
      condensed with 4-(N-methylamino)benzoic acid and the resulting product was
      annulated with formamidine or acetamidine acetate to obtain the 2-desamino and 2
      desamino-2-methyl analogues, respectively, of 4-amino-4-deoxy-N10-methylpteroic
      acid. Condensation with di-tert-butyl L-glutamate in the presence of diethyl
      phosphorocyanidate followed by ester cleavage with trifluoroacetic acid was then
      carried out. Retention of the L configuration in the glutamate moiety during this
      synthesis was demonstrated by rapid and essentially complete hydrolysis with
      carboxypeptidase G1 under conditions that likewise cleaved the L enantiomer of
      MTX but left the D enantiomer unaffected. The 2-desamino and 2-desamino-2-methyl
      analogues of AMT and MTX inhibited the growth of tumor cells, but were very poor
      inhibitors of dihydrofolate reductase (DHFR). These unexpected results suggested
      that activity in intact cells was due to metabolism of the 2-desamino compounds
      to polyglutamates.

PMID- 1992123
TI  - Nucleosides and nucleotides. 94. Radical deoxygenation of tert-alcohols in 1-(2-C
      alkylpentofuranosyl) pyrimidines: synthesis of (2'S)-2'-deoxy-2'-C
      methylcytidine, an antileukemic nucleoside.
AB  - (2'S and 2'R)-2'-Deoxy-2'-C-methylcytidine (1i and 15) and (2'S)-2'-deoxy-2'-C
      ethylcytidine (1j) have been synthesized from the corresponding 2'-C
      alkylarabinofuranosyl- or -ribofuranosylpyrimidine derivatives 3 and 4 by radical
      deoxygenation of the methyl oxalyl esters of the 2'-tert-alcohol, followed by
      sequential deblocking and amination at the 4-position. (2'S)-2'-Deoxy-2'-C-methyl
      5-methyluridine (8) has also been synthesized in a similar manner. Among them,
      compound 1i exhibits the most potent cytotoxicity to L1210 cells with potency
      comparable to that of 1-beta-D-arabinofuranosylcytosine (1a). The size of the 2'
      substituents and the configuration at the 2'-position are the most important for
      the cytotoxicity. Cytotoxicity in vitro of 1i against various human cancer cell
      lines was also examined and compared with that of 1a and 5-fluorouracil.

PMID- 1992125
TI  - A cardioselective, hydrophilic N,N,N-trimethylethanaminium alpha-tocopherol
      analogue that reduces myocardial infarct size.
AB  - The alpha-tocopherol analogue 3,4-dihydro-6-hydroxy-N,N,N,2,5,7,8- heptamethyl-2H
      1-benzopyran-2-ethanaminium 4-methylbenzenesulfonate (1a, MDL 73404) and its O
      acetate 1b (MDL 74270) were synthesized. Compound 1a was found to be hydrophilic
      (log P = -0.60) and to prevent lipid autoxidation in rat brain homogenate with an
      IC50 of 1.7 +/- 0.9 microM. Tissue distribution studies with [14C]-1b in rats (1
      mg/kg iv) showed that radioactivity accumulates in the heart (ratio 20:1 vs blood
      after 1 h). Infusion of 1 mg/kg per h of 1b bromide reduced infarct size by 54%
      in rats subjected to coronary artery occlusion for 60 min followed by reperfusion
      for 30 min, compared to saline-infused controls. By comparison, the tertiary
      amine analogue 5 was found not to accumulate in heart tissue, to be an equally
      effective free-radical scavenger in vitro, but to require a higher dose to reduce
      infarct size in rats. This shows that the cardioselectivity of compound 1
      contributes to its potency in salvaging myocardial tissue in rats after ischemia
      and reperfusion.

PMID- 1992124
TI  - Synthesis and evaluation of DNA-targeted spatially separated bis(aniline
      mustards) as potential alkylating agents with enhanced DNA cross-linking
      capability.
AB  - DNA-targeted separated bis-mustards were synthesized by attaching aniline mono
      mustards at the 4- and 9-positions of the DNA-intercalating ligand 9
      aminoacridine-4-carboxamide, with the intention of improving the low cross-link
      to monoadduct ratio found with most alkylating agents. The geometry of these
      compounds requires that, when the acridine binds to DNA by intercalation, one
      alkylating moiety is delivered to each DNA groove. Gel electrophoretic studies
      show that only one arm of these compounds (probably that attached to the 9
      position) alkylates DNA, such alkylation occurring specifically in the major
      groove at the N7 of guanines. Cell-line studies confirm that the mode of
      cytotoxicity of these compounds (unlike that of untargeted aniline bis-mustards
      of comparable reactivity) is due to bulky DNA monoadduct formation. It is
      concluded that more information is required about the exact orientation of the
      initial monoadducts before ligands with specific DNA cross-linking ability can be
      designed.

PMID- 1992126
TI  - Dual inhibitors of thromboxane A2 synthase and 5-lipoxygenase with scavenging
      activity of active oxygen species. Synthesis of a novel series of (3
      pyridylmethyl)benzoquinone derivatives.
AB  - A novel series of (3-pyridylmethyl)benzoquinone derivatives was molecular
      designed and synthesized for the dual purpose of inhibiting thromboxane A2 and
      leukotriene biosynthesis enzymes and scavenging active oxygen species (AOS). They
      were evaluated for inhibition of TXA2 synthase, inhibition of 5-lipoxygenase, and
      for their scavenging activity of AOS using the thiobarbituric acid method. 2,3,5
      Trimethyl-6-(3-pyridylmethyl)-1,4-benzoquinone (24, CV-6504) was the most
      promising derivative since it showed efficient AOS scavenging activity
      (inhibition of lipid peroxidation in rat brain homogenates: IC50 = 1.8 x 10(-6)
      M) as well as potent, specific, and well-balanced inhibitory effects on both
      enzymes (inhibitory effect on TXA2 synthase in human blood, IC50 = 3.3 x 10(-7)
      M; inhibitory effect on 5-lipoxygenase in human blood, IC50 = 3.6 x 10(-7) M). In
      adriamycin-induced proteinuria in a rat model, compound 24 at 10 mg/kg per day
      (po) suppressed proteinuria by more than 50%. The proteinuria, however, could not
      be reduced by single administration of an inhibitor specific for thromboxane A2
      synthase [(E)-7-phenyl-7-(3-pyridyl)-6-heptenoic acid (2, CV-4151)] or for 5
      lipoxygenase [2-(12-hydroxy-5,10-dodecadiynyl)-3,5,6-trimethyl-1,4-benzoquinone
      (1, AA-861)]. The proteinuria was also not reduced by administration of an AOS
      scavenger, 2-O-octadecylascorbic acid (4, CV-3611). Triple function compounds
      such as compound 24 that specifically inhibit both enzymes as well as scavenge
      AOS possess a variety of pharmacologically beneficial effects.

PMID- 1992127
TI  - 2,3-Dihydrobenzofuran analogues of hallucinogenic phenethylamines.
AB  - Two 2,3-dihydrobenzofuran analogues of hallucinogenic amphetamines were prepared
      and evaluated for activity in the two-lever drug-discrimination paradigm in rats
      trained to discriminate saline from LSD tartrate (0.08 mg/kg) and for the ability
      to displace [125I]-(R)-DOI [( 125I]-(R)-1-(2,5-dimethoxy-4-iodophenyl)-2
      aminopropane) from rat cortical homogenate 5-HT2 receptors. The compounds, 1-(5
      methoxy-2,3-dihydrobenzofuran-4-yl)-2-aminopropane (6a) and its 7-brominated
      analogue 6b, possessed activity comparable to their conformationally flexible
      counterparts 1-(2,5-dimethoxyphenyl)-2-aminopropane (3) and its 4-bromo
      derivative DOB (5), respectively. The results suggest that the dihydrofuran ring
      in 6a and 6b models the active conformation of the 5-methoxy groups in 3 and 5.
      Free energy of binding, derived from radioligand displacement KA values,
      indicated that addition of the bromine in either series contributes 2.4-3.2
      kcal/mol of binding energy. On the basis of surface area of the bromine atom,
      this value is 2-3 times higher than would be expected on the basis of hydrophobic
      binding. Thus, hydrophobicity of the para substituent alone cannot account for
      the dramatic enhancement of hallucinogenic activity. Although this substituent
      may play a minor role in orienting the conformation of the 5-methoxy group in
      derivatives such as 4 and 5, there appears to be some other, as yet unknown,
      critical receptor interaction.

PMID- 1992128
TI  - Fluoronaphthyridines and -quinolones as antibacterial agents. 3. Synthesis and
      structure-activity relationships of new 1-(1,1-dimethyl-2-fluoroethyl), 1-[1
      methyl-1-(fluoromethyl)-2-fluoroethyl], and 1-[1,1-(difluoromethyl)-2
      fluoroethyl] substituted derivatives.
AB  - A series of novel N-1-(mono-,-(di- and -(trifluoro-tert-butyl)quinolones and 
      naphthyridines has been prepared. Structure-activity relationship (SAR) studies
      indicated that the in vitro antibacterial potency was the following order: 1-(1,1
      dimethyl-2-fluoroethyl) greater than 1-[1-methyl-1-(fluoromethyl)-2-fluoroethyl]
      greater than 1-[1,1-(difluoromethyl)-2-fluoroethyl] substituents. In the
      quinolone series the monofluoro-tert-butyl derivatives were found to possess
      better in vitro antibacterial activity than the nonfluorinated-tert-butyl
      equivalents. In vivo PD50 values of the 1-fluoro-tert-butyl-substituted
      derivatives reflect pharmacokinetic behavior and incomplete oral absorption.

PMID- 1992129
TI  - Calcium-independent phosphodiesterase inhibitors as putative antidepressants: [3
      (bicycloalkyloxy)-4-methoxyphenyl]-2-imidazolidinones.
AB  - The synthesis and biological properties of a novel series of selective calcium
      independent phosphodiesterase inhibitors are described. These compounds also
      inhibit the specific binding of [3H]rolipram to rat brain membranes and exhibit
      efficacy in preclinical models of antidepressant activity in mice, such as
      reducing immobility in the forced-swim test and reversing reserpine-induced
      hypothermia. Imidazolidinones 4 and 16 were found to be the most potent compounds
      studied.

PMID- 1992130
TI  - Antioxidant activity of probucol and its analogues in hypercholesterolemic
      Watanabe rabbits.
AB  - Probucol (1) and probucol analogues with the substitutions at the disulfide
      linked carbon (2, 3) and an additional substitution at a tert-butyl of each
      phenolic ring (4) were tested for their ability to lower total serum cholesterol
      and prevent aortic atherosclerosis in modified Watanabe heritable hyperlipidemic
      (WHHL) rabbits and to inhibit Cu2(+)-induced lipid peroxidation of isolated
      plasma low-density lipoproteins (LDL). After 84 days of feeding 1% of each
      compound in rabbit chow, probucol was effective in lowering serum cholesterol,
      whereas 2-4 were not. The concentration of drug in serum and LDL was 2 greater
      than 1 greater than 3 greater than 4. Probucol and analogues prevented Cu2(+)
      induced oxidation of LDL in vitro to an extent that directly related to their
      concentrations in LDL. The decrease in lipid oxidation was directly correlated
      with the inhibition of both oxidized-LDL-induced cholesteryl ester synthesis in
      cultured macrophages and to the inhibition of aortic atherosclerosis in vivo.
      These results show that the antioxidant activity of probucol and analogues is
      directly related to their concentration in LDL, which may explain their
      pharmacological activity in reducing atherosclerosis.

PMID- 1992131
TI  - N-[(omega-amino-1-hydroxyalkyl)phenyl]methanesulfonamide derivatives with class
      III antiarrhythmic activity.
AB  - N-[4-[4-(Ethylheptylamino)-1-hydroxybutyl]phenyl]methanesulfonamid e, (E)-2
      butenedioate (2:1) salt (ibutilide fumarate, 2E), has been found to have Class
      III antiarrhythmic activity. In an in vitro rabbit heart tissue preparation
      designed to evaluate the cardiac electrophysiology of potential antiarrhythmic
      agents, it selectively prolongs the effective refractory period of papillary
      muscle. In vivo it increases the ventricular refractory period of the canine
      heart and prevents the ventricular arrhythmias induced by programmed electrical
      stimulation 3-9 days after a myocardial infarction. This paper describes the
      synthesis of 2E and a series of related compounds. The in vitro evaluation of the
      cardiac electrophysiology of these compounds has allowed us to determine the
      structural requirements for Class III antiarrhythmic activity in this series.
      Evaluation of the antiarrhythmic activity of 2E and one of the more potent
      analogues on the late postinfarction ventricular arrhythmias induced by
      programmed electrical stimulation of the canine myocardium is also described.
      This activity is compared with that of the Class III antiarrhythmic agent
      sotalol. Compound 2E appears to be as effective and 10-30 times more potent than
      sotalol in this model.

PMID- 1992132
TI  - Boron-containing thiouracil derivatives for neutron-capture therapy of melanoma.
AB  - Boron-containing derivatives of 2-thiouracil and 2,4-dithiouracil and the
      corresponding 6-propyl compounds, containing a dihydroxyboryl group in the 5
      position, have been prepared. These compounds accumulate in B16 melanoma in mice
      in concentrations up to 30 micrograms of boron per gram tissue. The uptake
      persists. The toxicity of both 2-thiouracil derivatives is low. These compounds
      are therefore good candidates for boron neutron-capture therapy of malignant
      melanoma.

PMID- 1992133
TI  - Substituted dihydrobenzopyran and dihydrobenzofuran thiazolidine-2,4-diones as
      hypoglycemic agents.
AB  - A series of dihydrobenzofuran and dihydrobenzopyran thiazolidine-2,4-diones
      (compounds 3-26) was synthesized from the corresponding aryl aldehydes 1 in two
      steps. These compounds represent conformationally restricted analogues of the
      novel hypoglycemic ciglitazone. The series was evaluated by hypoglycemic effects
      in vitro by measuring stimulation of 2-deoxyglucose uptake in L6 myocytes and
      stimulation of expression of the glucose transporter protein in 3T3-L1
      adipocytes. In vivo hypoglycemic effects were evaluated in the genetically obese
      ob/ob mouse, and structure-activity relationships are discussed. On the basis of
      this in vivo potency, we have selected the 2(R)-benzylbenzopyran derivative to be
      further studied in a clinical setting.

PMID- 1992135
TI  - A ring-enlarged oxetanocin A analogue as an inhibitor of HIV infectivity.
AB  - Two ring-expanded analogues (compounds 2 and 3) of the anti-HIV fermentation
      product oxetanocin A (1) were synthesized from commercially available diacetone D
      glucose. Antiviral testing against HIV in ATH8 cells revealed that the ring
      expanded analogue 2 possessed a similar activity profile as oxetanocin A. Neither
      compound, however, was capable of providing full protection to the cells against
      HIV infection. The isomeric ring-expanded analogue 3 was totally devoid of anti
      HIV activity. Molecular modeling suggested that while oxetanocin A and compounds
      2 and 3 share a large common substructure with the potent anti-HIV drug,
      dideoxyadenosine (ddA), the extra hydroxymethyl substituent may contribute
      negatively to the binding of these molecules to a critical enzyme. The negative
      contribution may be less important in oxetanocin and isomer 2 than in isomer 3.
      From these studies it would appear that both oxetane and tetrahydrofuran rings
      are equivalent templates to support the adenine base in terms of anti-HIV
      activity.

PMID- 1992134
TI  - Chemical and biological studies on a series of lipid-soluble (trans-(R,R)- and 
      (S,S)-1,2-diaminocyclohexane)platinum(II) complexes incorporated in liposomes.
AB  - cis-Bis(neodecanoato)(trans-(R,R)-1,2-diaminocyclohexane)platinum( II) [L-NDDP]
      is a liposome incorporated lipophilic cisplatin analogue that has shown promising
      antitumor activity against tumors resistant to cisplatin and liver metastases in
      mice. L-NDDP is currently under clinical evaluation. However, NDDP is an isomeric
      mixture of different species having various isomeric neodecanoic moities as
      liganded leaving groups. A series of new highly lipid-soluble cis
      bis(neodecanoato)(trans-(R,R)- and -(S,S)-1,2-diaminocyclohexane)platinum(II)
      [Pt] complexes, using single isomers of neodecanoic acid, were synthesized and
      characterized by analytical and spectroscopic techniques (infrared and 195Pt
      NMR). Multilamellar vesicles (MLVs) composed of dimyristoylphosphatidylcholine
      (DMPC) and dimyristoylphosphatidylglycerol (DMPG) at a molar ratio of 7:3 were
      used as carriers of the Pt complexes. The efficiency of incorporation of the
      liposomal-platinum (L-Pt) preparations was greater than 95% and stability in
      normal saline at 4 degrees C was greater than 95% at day 14 in each case. The iv
      LD50 values of all L-Pt preparations tested were in the range of 62.3 to 104
      mg/kg. The % T/C obtained after a single ip injection of the optimal dose of L-Pt
      preparations against L1210 leukemia was in the range of 150 to 253 (160 for
      cisplatin). When a multiple ip injection schedule was used (on days 1, 5, and 9)
      the L-Pt preparations of R,R complexes (1, 7, and 9) were more active than
      cisplatin at the optimal dose (% T/C = 257 for each vs 220 for cisplatin). The L
      Pt preparations of R,R complexes were also markedly active against L1210 leukemia
      resistant to cisplatin (% T/C 355, 231, and 185 respectively vs 112 for
      cisplatin). These studies show that the single isomers of NDDP are comparable to
      the original isomeric mixture in terms of toxicity and biological activity.

PMID- 1992136
TI  - A new class of HIV-1-specific 6-substituted acyclouridine derivatives: synthesis
      and anti-HIV-1 activity of 5- or 6-substituted analogues of 1-[(2
      hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT).
AB  - A series of novel acyclouridine derivatives substituted at both the C-5 and C-6
      positions were synthesized for the purpose of improving the activity of a
      recently reported HIV-1-specific lead, 1-[(2-hydroxyethoxy)methyl]-6
      (phenylthio)thymine (HEPT). Preparation of C-6 substituted derivatives was
      carried out based on the following three methods: (1) LDA (lithium
      diisopropylamide) lithiation of a thymine derivative (4) and subsequent reaction
      with electrophiles, (2) an addition-elimination reaction of HEPT or its 6
      (phenylsulfinyl) derivative (10), or (3) palladium-catalyzed cross-coupling
      between a 6-iodo derivative (16) and terminal alkynes. Following the methods, 21
      C-6 substituted analogues were synthesized. Among these, 6-(cyclohexylthio) (8),
      6-phenoxy (13), and 6-benzyl (27) derivatives showed anti-HIV-1 (HTLV-IIIB)
      activity with EC50 values of 8.2, 85, and 23 microM, respectively. Preparation of
      C-5 substituted derivatives was based on either LTMP (lithium 2,2,6,6
      tetramethylpiperidide) lithiation of 6-(phenylthio)uracil derivative 37 or the
      above mentioned palladium-catalyzed cross-coupling of a 5-iodo-6
      (phenylthio)uracil derivative (38). Following these methods, 11 C-5 substituted
      analogues were synthesized. Some 5-substituted derivatives (5-I, 44; 5-CH = CPh2,
      49; 5-CH = CHPh (Z), 54; and 5-CH = CH2, 55) were more active than HEPT, but
      their selectivity indices (SI = CC50/EC50) were lower than that of HEPT. Compound
      8 was also evaluated against another HIV-1 strain (HTLV-IIIRF) and HIV-2 strains
      (LAV-2ROD and LAV-2EHO). Only HTLV-IIIRF was as sensitive as HTLV-IIIB.

PMID- 1992137
TI  - Inhibitors of cholesterol biosynthesis. 3. Tetrahydro-4-hydroxy-6-[2-(1H-pyrrol-1
      yl)ethyl]-2H-pyran-2-one inhibitors of HMG-CoA reductase. 2. Effects of
      introducing substituents at positions three and four of the pyrrole nucleus.
AB  - A series of trans-tetrahydro-4-hydroxy-6-[2-(2,3,4,5-substituted-1H-pyrrol-1-yl)
      ethyl]-2H-pyran-2-ones and their dihydroxy acids were prepared and tested for
      their ability to inhibit the enzyme HMG-CoA reductase in vitro. Inhibitory
      potency was found to increase substantially when substituents were introduced
      into positions three and four of the pyrrole ring. A systematic exploration of
      structure-activity relationships at these two positions led to the identification
      of a compound ((+)-33,(+)-(4R)-trans-2-(4-fluororphenyl)-5-(1-methylethyl)-N,3-
      diphenyl-1- [(tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl]-1H-pyrrole-4-
      carboxamide) with five times the inhibitory potency of the fungal metabolite
      compactin.

PMID- 1992139
TI  - Disubstituted tetrahydrofurans and dioxolanes and PAF antagonists.
AB  - A new series of disubstituted tetrahydrofuran and dioxolane derivatives were
      prepared and evaluated for their PAF antagonist activity in the PAF-induced in
      vitro platelet-aggregation and in vivo hypotension tests. Several of these
      compounds exhibited more potent activity than the structurally related 2-[N
      acetyl-N-[[[[2-methoxy-3-[(octadecylcarbamoyl) oxy]propoxy]carbonyl]amino]methyl]
      1-ethylpyridinium chloride (CV-6209, 3) in the in vitro assay, whereas all showed
      less potency in the in vivo test. The role of both the substituent nature and the
      placement and number of oxygen atoms in the ring are discussed. A quantitative
      SAR study carried out on these nuclei.

PMID- 1992138
TI  - Inhibitors of cholesterol biosynthesis. 4. trans-6-[2-(substituted
      quinolinyl)ethenyl/ethyl]tetrahydro-4-hydroxy-2 H-pyran-2-ones, a novel series of
      HMG-CoA reductase inhibitors.
AB  - A series of substituted quinoline mevalonolactones were prepared and evaluated
      for their ability to inhibit the enzyme HMG-CoA reductase both in vitro and
      (cholesterol biosynthesis) in vivo. Since previous studies suggested that the 4
      (4-fluorophenyl) and 2-(1-methylethyl) substituents afforded optimum potency,
      attention was focused on variations at position 6 of the quinoline ring.
      Biological evaluation of a small number of analogues bearing a variety of 6
      substituents showed that modification at this position had little effect on
      potency. Several compounds (8b, 8e, and 11) were identified that showed
      comparable potency to compactin and mevinolin in both the in vitro and in vivo
      assays.

PMID- 1992140
TI  - Heterocyclic quinones. 17. A new in vivo active antineoplastic drug: 6,7-bis(1
      aziridinyl)-4-[[3-(N,N-dimethylamino)propyl]amino]-5,8- quinazolinedione.
AB  - A series of heterocyclic quinones, 6-substituted and 6,7-disubstituted 4
      (alkylamino)-5,8-quinazolinediones, have been synthesized in order to evaluate
      their in vitro cytotoxicity on L1210 leukemia cells. Among 14 derivatives that
      have been prepared and studied for the structure-activity relationship, the most
      potent cytotoxic compound on L1210 leukemia cells was the 6,7-bis(1-aziridinyl)-4
      [[3-(N,N-dimethylamino)propyl]amino]-5,8- quinazolinedione (24). This compound
      has been tested with the use of a cell-image processor on MCF-7 human mammary and
      HBL human melanoma cell lines. The results show that compound 24 influences cell
      proliferation and blocks both cells lines in the S phase. In vivo antineoplastic
      activity of compound 24 has been demonstrated on a broad spectrum of murine
      experimental models, but it was found highly toxic and produced long-delayed
      deaths.

PMID- 1992141
TI  - Synthesis and anticonvulsant activity of imidooxy derivatives.
AB  - Previous results of anticonvulsant activity in several imidooxy carboxylates
      related to (aminooxy)acetic acid in young chicks, prompted an in-depth
      reinvestigation of these analogues in mice. A series of 22 succinimidooxy,
      phthalimidooxy, and naphthalimidooxy carboxylates were synthesized and evaluated
      for anticonvulsant activity by the National Institute of Neurological and
      Communicative Disorders and Stroke (NINCDS). Methyl (succinimidooxy)acetate (2d),
      ethyl (succinimidooxy)acetate (2e), methyl (phthalimidooxy)acetate (3d), ethyl
      (phthalimidooxy)acetate (3e), and ethyl 2-(phthalimidooxy)propionate (3g), which
      were initially found to be active as anticonvulsants in young chicks were
      uniformly inactive in the Phase I seizure tests involving maximal electroshock
      (MES), pentylenetetrazol (scMet), or neurologic toxicity toxicity (Tox). Several
      newer analogues, ethyl (succinimidooxy)formate (2c) and methyl 3-(phthalimidooxy)
      2-methylacrylate (4h) were found to be active in the scMet (3a) or both (4h)
      evaluations. Most interesting was the anticonvulsant results of N-(benzyloxy)-2
      azaspiro[4,4] nonane-1,3-dione (5b), which displayed anti-MES activity and a
      protective index (TD50/ED50) of greater than 4.5.

PMID- 1992142
TI  - Preparation, characterization, and anticancer activity of a series of cis-PtCl2
      complexes linked to anthraquinone intercalators.
AB  - A new series of complexes of the type cis-PtL2X2 [where L is a monodentate AQ
      Y(CH2)nNH2 and L2 is a bidentate AQ-Y(CH2)nNH(CH2)2NH2; AQ = anthraquinone, X =
      Cl, I, Y = NH, O] in which anthraquinone intercalators are tethered to the cis
      PtCl2 unit via an (aminoalkyl)amino, (oxyalkyl)amino, or polyethylene glycol
      (aminoethyl)amino linker chains was prepared and screened in vitro against P388
      leukemia. In vivo toxicity studies were carried out on selected complexes. All
      complexes were characterized by means of elemental analysis, 195Pt NMR
      spectroscopy, and FTIR. The 1:1 Pt-intercalator complexes displayed much higher
      in vitro cytotoxic activities than the 1:2 Pt-intercalator complexes. The
      dichloride complexes were consistently more active than their diiodide
      counterparts. Among the 1:1 Pt-intercalator complexes those with the shorter
      linker chains (n = 2, 3) exhibited the highest cytotoxic activities. Three
      compounds, [[2-[[2-(anthraquinon-1- ylamino)ethyl]amino]ethyl]amine
      N,N']dichloroplatinum(II), [[2-[[3-(anthraquinon-1
      ylamino)propyl]amino]ethyl]amine- N,N']dichloroplatinum(II), and [[2-[[3
      anthraquinon-1- yloxy)propyl]amino]ethyl]amine-N,N']dichloroplatinum(II), were as
      active in vitro as cisplatin (ED50 = 2-4 x 10(-7) M) while on a molar basis their
      acute in vivo toxicity was significantly lower than that of cisplatin. In vivo
      screening against P388 leukemia indicated that these complexes have activity
      comparable to cisplatin.

PMID- 1992144
TI  - Novel heteroarotinoids: synthesis and biological activity.
AB  - In this study, 13 heteroarotinoids were synthesized. The key step in each
      preparation was the condensation of the appropriate chroman-, thiochroman-, or
      benzothienyl-substituted phosphorus ylide, obtained from the independent
      synthesis of the corresponding phosphonium salts, with selected polyene
      substituted aldehyde esters. Nine of these heterocycles contained a thiochroman
      group, two had a chroman group, and two others had a benzothienyl system.
      Screening of the compounds was with one of two assays. One assay measured the
      ability of a retinoid to inhibit the phorbol ester induced increase of mouse
      epidermal ornithine decarboxylase (ODC) activity. The other assay measured
      retinoid-induced differentiation of the human myoloid leukemia cell line HL-60.
      In the ODC assay, all thirteen compounds were screened. The most active
      heteroarotinoids were ester 10 [methyl (E)-4-[2-(2,2,4,4-tetramethylthiochroman-6
      yl)-1- propenyl]benzoate] and acid 11 [(E)-4-[2-(2,2,4,4-tetramethyl-3,4- dihydro
      2H-1- benzothiopyran-6-yl)-1-propenyl]benzoic acid]. Both of these retinoids had
      ID50 values (dose required for half-maximal inhibition of phorbol ester induced
      ODC activity) of about 0.3 nmol. In comparison, the ID50 value for trans-retinoic
      acid (1) was 0.12 nmol while the ID50 values for acids 7 and 9, namely (2Z,4E,6E)
      3,7-dimethyl-7-(4,4-dimethyl-thiochroman -6-yl)-2,4,6-heptatrienoic acid and
      (2E,4E,6E)-3,7-dimethyl-7-(2,2,4,4-tetramethylthiochroman -6-yl)-2,4,6-
      heptatrienoic acid, respectively, were about 3.5 nmol. Heteroarotinoids 8 and 12
      17 had ID50 values of 35 nmol or greater. With a thiochroman unit, the most
      active acids in decreasing order of activity in the ODC assay were 7 greater than
      9 greater than 8. Thus, simple replacement of the terminal propenyl system
      [C(16,17,18)] in 7 with a cyclopropyl group produced acid 8 [(2E,4E,6E)-7-methyl
      7-(4,4-dimethylthiochroman-6-yl)- 2,3-methylene-4,6-heptadienoic acid with
      markedly reduced activity. With a benzoic acid group as part of the structure
      attached to the thiochroman unit, the ODC activity was enhanced as shown in 10
      and 11. The combination of the 2,2,4,4-tetramethylthiochroman group and the
      benzoic acid (or ester) terminal group seemed to enhance the biological action
      which resembles that found with (E)-4-[2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl
      2-naphthalenyl)- 1-propenyl]benzoic acid (TTNPB, 6b), a well-known model
      system.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1992143
TI  - Unsaturated and carbocyclic nucleoside analogues: synthesis, antitumor, and
      antiviral activity.
AB  - A series of unsaturated analogues of nucleosides were prepared and their
      cytotoxic, antitumor, and antiviral activities were investigated. Alkylation of
      cytosine with (E)-1,4-dichloro-2-butene gave chloro derivative 2f, which was
      hydrolyzed to alcohol 2h. Cytosine, adenine, 2-amino-6-chloropurine, thymine, and
      (Z)-1,4-chloro-2-butene gave compounds 4c-f, which, after hydrolysis, afforded
      alcohols 4a, 4b, 4g, and 4h. Alkenes 4d and 4e were cyclized to heterocycles 12
      and 13. Alkylation of 2,6-diaminopurine with 1,4-dichloro-2-butyne led to chloro
      derivative 6a, which was hydrolyzed to alcohol 6b. Allenic isomerization of 6b
      gave compound 5c. Chloro derivatives 2e-g, 4c-f, 5d, and 6c-e as well as
      pyrimidine oxacyclopentenes 9c and 9d are slow-acting inhibitors of murine
      leukemia L1210 of IC50 10-100 microM. The most active were analogues 4c, 4d, 4e,
      and 6e (IC50 10-20 microM). The corresponding hydroxy derivatives were less
      active of inactive. Inhibition of macromolecular synthesis with compounds 4c, 4d,
      6e, 9c, and 9d follows the order: DNA greater than RNA greater than or equal to
      protein. Cytotoxic effects of 4c, 6e, and 9d are not reversed with any of the
      four basic ribonucleosides or 2'-deoxyribonucleosides. Inhibitory activity of
      cytosine derivative 9c is reversed with uridine and 2'-deoxyuridine but not with
      the corresponding cytosine nucleosides. Zone assays in several tumor cell lines
      show that active compounds are cytotoxic agents with little selectivity for tumor
      cells. Analogue 6c showed 16.7% ILS in leukemia P388/o implanted ip in mice at
      510 and 1020 mg/kg, respectively. Cytallene (5b) and 6'beta-hydroxyaristeromycin
      (10) exhibited significant activity against Friend and Rauscher murine leukemia
      viruses. The rest of the hydroxy derivatives, with the exception of 4a, were
      moderately effective or inactive as antiviral agents. None of the chloro
      derivatives or oxacyclopentenes exhibited an antiviral effect at noncytotoxic
      concentrations. Z-Olefin 4b and 2-aminoadenallene (5c) are substrates for
      adenosine deaminase.

PMID- 1992145
TI  - Design, synthesis, and physicochemical properties of a novel, conformationally
      restricted 2,3-dihydro-1,3,4-thiadiazole-containing angiotensin converting enzyme
      inhibitor which is preferentially eliminated by the biliary route in rats.
AB  - Two novel series of dihydrothiadiazole ring containing inhibitors of angiotensin
      converting enzyme have been designed and synthesized. The compounds are highly
      potent enzyme inhibitors and, as a consequence of conformational restriction,
      chemically stable with respect to undesirable cyclization reactions. The most
      interesting compound from this series, 5a (FPL 63547), is the monoethyl ester
      prodrug of the highly potent "aminocarboxy" inhibitor 5b (FPL 63674). It produces
      an antihypertensive effect of long duration in animal models after oral dosing.
      Unlike other ACE inhibitors, 5b is eliminated almost entirely by biliary
      clearance in the rat. The favorable pharmacological properties of 5a and 5b are
      rationalized in terms of their unique physicochemical profiles. The clear
      preference for biliary clearance seen with 5b is consistent with its
      lipophilicity and its high degree of net ionization at physiological pH, which
      results from the very low pKa of the C-terminus carboxylic acid function. FPL
      63547 is presently undergoing clinical investigation in man.

PMID- 1992146
TI  - Non-steroidal antiandrogens. Design of novel compounds based on an infrared study
      of the dominant conformation and hydrogen-bonding properties of a series of
      anilide antiandrogens.
AB  - Antiandrogenic activity is observed in anilides containing a tertiary hydroxyl
      group, and these compounds are used to define a pharmacophore in terms of their
      physicochemical properties. Infrared spectroscopy shows that these anilides exist
      in a single conformation, which exerts a powerful influence on the hydrogen-bond
      donor ability of the hydroxyl group in a model system. Arguments are presented
      which suggest that hydrogen-bonding ability is an important contributor to
      biological activity. Compounds were synthesized that reproduced these properties
      in series not containing an amide bond. Such compounds were found to exhibit good
      antiandrogen activity. We suggest that quantitative information on hydrogen
      bonding might also be useful in other systems.

PMID- 1992147
TI  - trans-3-n-propyl-L-proline is a highly favorable, conformationally restricted
      replacement for methionine in the C-terminal tetrapeptide of cholecystokinin.
      Stereoselective synthesis of 3-allyl- and 3-n-propyl-L-proline derivatives from 4
      hydroxy-L-proline.

PMID- 1992148
TI  - Folic acid analogues lacking the 2-carbon are substrates for folylpolyglutamate
      synthetase and inhibit cell growth.

PMID- 1992149
TI  - Relationship between tissue selectivity and lipophilicity for inhibitors of HMG
      CoA reductase.

PMID- 1992150
TI  - 8-(Dicyclopropylmethyl)-1,3-dipropylxanthine: a potent and selective adenosine A1
      antagonist with renal protective and diuretic activities.

PMID- 1992151
TI  - Design of a well-absorbed renin inhibitor.

PMID- 1992152
TI  - Absolute structure-cytotoxic activity relationships of steganacin congeners and
      analogues.
AB  - The cytotoxic activities of optically pure and racemic steganacin congeners and
      analogues against KB cells in culture and the inhibitor activity of cilia
      regeneration in Tetrahymena were studied with regard to absolute and relative
      configurations. The stereochemical requirements of dibenzocyclooctadiene lignan
      lactones for activity were clarified.

PMID- 1992153
TI  - Synthesis and structure-activity relationships of benzo[b]thienylallylamine
      antimycotics.
AB  - Benzo[b]thiophene analogues of the allylamine antimycotic terbinafine (2) bearing
      the side chain at various positions and optionally substituted by halogen have
      been prepared and their antifungal activity studied. Derivatives bearing the side
      chain at positions 3, 4, or 7 are bioequivalents of 2. Compounds containing the
      allylamine side chain at position 7, with a further substituent at position 3,
      showed significantly enhanced activity against Candida albicans, an effect which
      appears to be specifically linked only to this particular substitution pattern. 3
      Chloro-7-benzo[b]thienyl derivative 7m was found to be the most potent allylamine
      antimycotic identified so far. In general, substituted benzo[b]thiophenes can be
      used not only as potential equivalents of naphthalene in bioactive compounds but
      also as a tool to selectively modify biological activities.

PMID- 1992154
TI  - Synthesis and antiarrhythmic activity of alpha-[(diarylmethoxy)methyl]-1
      piperidineethanols.
AB  - A series of alpha-[(diarylmethoxy)methyl]-1-piperidineethanols was evaluated for
      antiarrhythmic activity in the coronary artery ligated dog model. Structure
      activity relationship studies indicated that the 2,6-dimethylpiperidine group
      afforded the best antiarrhythmic agents in this series and was essential for long
      duration of action. This investigation indicated that quaternary ammonium salts
      were not essential for a long duration of action. It was also shown that the
      antiarrhythmic activity could be separated from the tachycardia frequently caused
      by this type of agent.

PMID- 1992155
TI  - Design of potent protein kinase inhibitors using the bisubstrate approach.
AB  - A new class of serine/threonine protein kinase inhibitors was designed by
      associating, in the same structure, mimics of both the ATP binding site and a
      protein substrate. Among the several potent antagonists which were obtained, the
      most active consists of isoquinoline-5-sulfonamide, as ATP mimic, and Ser-Arg6,
      as peptidic moiety, bound by a-NH(CH2)2NH(CH2)2CO-linker. This compound, with a
      Ki of 0.1 microM toward protein kinase C (PKC) and 0.004 microM toward cyclic AMP
      dependent protein kinase (PKA), is respectively 60- and 750-fold more active than
      the commercial inhibitor H-7.

PMID- 1992156
TI  - (Acyloxy)alkyl carbamate prodrugs of norfloxacin.
AB  - As a new prodrug approach to norfloxacin (NFLX) we prepared the acetoxyalkyl
      carbamates of the type NFLX-CO-OCHR-OAc by the reaction of sodium or mercuric
      acetate on NFLX alpha-chloroalkyl carbamates. These produrgs did not have the
      bitter taste of NFLX. In vitro, the acetoxyethyl carbamate exhibited activity
      only against Staphylococcus spp. and was inactive against Gram-negative
      organisms. However, in the presence of serum and intestinal homogenate, esterase
      catalyzed hydrolysis of the ester bond in these modified carbamates led to a
      cascade reaction resulting in the rapid regeneration of NFLX. At high oral doses
      of the prodrug, the acetaldehyde produced as a side product in the breakdown of
      the promoiety caused a slight decrease in alcohol metabolism in a mouse model.
      The bioavailability of NFLX from the acetoxyethyl carbamate was lower compared to
      an equivalent dose of NFLX when given as an oral suspension in rhesus monkeys,
      presumably because of the lower aqueous solubility of the prodrug.

PMID- 1992157
TI  - A new ionizable chromophore of 1,4-bis(alkylamino)benzo[g]phthalazine which
      interacts with DNA by intercalation.
AB  - The tricyclic heteroaromatic nucleus of 1,4-bis(alkylamino)benzo[g]phthalazine
      can be protonated at physiological pH, depending on the nature of the side
      chains. The interaction of the 3-methoxypropyl derivative with calf thymus and
      closed, circular DNA has been studied with UV-vis spectroscopy and NMR. The
      effect of drug binding on the topology of closed, circular DNA was determined by
      topoisomerase-I catalyzed relaxation of the complex followed by gel
      electrophoresis. The results strongly support intercalative binding and suggest
      that this series of compounds are promising targets for anticancer activity
      evaluation.

PMID- 1992158
TI  - Molecular analysis of ultraviolet-induced mutations in a xeroderma pigmentosum
      cell line.
AB  - We have isolated and characterized 47 ultraviolet light-induced hprt mutants from
      a simian virus 40-transformed excision-repair-deficient xeroderma pigmentosum
      cell line (complementation group A). Twenty-one independent mutations were found,
      of which the majority were point mutations. Eleven of these were identified as
      base changes, nine of which could be attributed to ultraviolet damage on the
      transcribed DNA strand. Both transitions and transversions were found among the
      single base changes. A large proportion of the mutations (13/21) resulted in
      aberrant splicing of the hprt gene, suggesting that the target size for mutations
      resulting in aberrant splicing must be quite large. A small number of spontaneous
      mutations were identified, most of which were large deletions. Our data provide a
      spectrum for the intrinsic mutations resulting from ultraviolet damage in human
      cells in the absence of repair.

PMID- 1992159
TI  - Regulation of filamentous bacteriophage length by modification of electrostatic
      interactions between coat protein and DNA.
AB  - Bacteriophage fd gene VIII, which encodes the major capsid protein, was mutated
      to convert the serine residue at position 47 to a lysine residue (S47K), thereby
      increasing the number of positively charged residues in the C-terminal region of
      the protein from four to five. The S47K coat protein underwent correct membrane
      insertion and processing but could not encapsidate the viral DNA, nor was it
      incorporated detectably with wild-type coat proteins into hybrid bacteriophage
      particles. However, hybrid virions could be constructed from the S47K coat
      protein and a second mutant coat protein, K48Q, the latter containing only three
      lysine residues in its C-terminal region. K48Q phage particles are approximately
      35% longer than wild-type. Introducing the S47K protein shortened these
      particles, the S47K/K48Q hybrids exhibiting a range of lengths between those of
      K48Q and wild-type. These results indicate that filamentous bacteriophage length
      (and the DNA packaging underlying it) are regulated by unusually flexible
      electrostatic interactions between the C-terminal domain of the coat protein and
      the DNA. They strongly suggest that wild-type bacteriophage fd makes optimal use
      of the minimum number of coat protein subunits to package the DNA compactly.

PMID- 1992160
TI  - Crystallization of complexes of EcoRV endonuclease with cognate and non-cognate
      DNA fragments.
AB  - Complexes of the type II restriction endonuclease EcoRV with a variety of short,
      selfcomplementary deoxyoligonucleotides have been crystallized. The best crystals
      diffract to about 2.7 A resolution and consist of 1:1 complexes between
      endonuclease dimers and duplexes of the cognate decamer GGGATATCCC containing the
      hexameric RV recognition sequence GATATC. Crystals with the non-cognate DNA
      octamer duplexes CGAGCTCG and CGAATTCG diffract to 3.0 and 3.5 A resolution,
      respectively, and contain two DNA duplexes per enzyme dimer.

PMID- 1992161
TI  - Identification of cis and trans-elements involved in the timed control of a
      Caulobacter flagellar gene.
AB  - The genes encoding the structural components of the Caulobacter crescentus
      flagellum are temporally controlled and their order of expression reflects the
      sequence of assembly. Transcription of the operon containing the structural gene
      for the flagellar hook protein occurs at a defined time in the cell cycle, and
      information necessary for transcription is contained within a region between -81
      and -120 base-pairs from the transcription start site. To identify the sequence
      elements that contribute to the temporal control of hook operon transcription, we
      constructed deletions and base changes in the 5' region and fused the mutagenized
      regulatory region to transcription reporter genes. We demonstrate that sequences
      3' to the transcription start site do not contribute to temporal control. We
      confirm that upstream sequences between -81 and -120 base-pairs are necessary for
      temporal activation, and that transcription also requires sequences at -26 to -46
      base-pairs. A specific binding activity for the region between -81 and -122 base
      pairs was shown to be temporally controlled, appearing prior to the activation of
      hook operon transcription. This binding activity was missing from strains
      containing mutations in flaO and flaW, two genes near the top of the flagellar
      hierarchy known to be required for hook operon transcription. Thus, the hook
      operon upstream region contains a sequence element that responds to a temporally
      controlled trans-acting factor(s), and in concert with a second sequence element
      causes the timed activation of transcription.

PMID- 1992162
TI  - Mapping using unique sequences.
AB  - Theoretical predictions are given for the progress expected, when mapping DNA by
      identifying clones containing specific unique sequences. Progress is measured in
      three ways; however, all results depend on (dimensionless counterparts of) the
      number of clones and the number of unique sequences used. Furthermore, the
      effects of clone length dispersion are included in the theoretical predictions.
      Both the clones in the library and the unique sequences are assumed to be
      generated randomly, with uniform probability of originating at any base in the
      region to be mapped. The first measure of progress is the expected length
      fraction of the region to be mapped covered by at least one clone, when clones
      containing at least one unique sequence are included in the map. The second
      measure of progress is the expected length fraction of the region to be mapped in
      "covered intervals", an interval being the region between adjacent unique
      sequences. Alternative definitions for clones covering an interval are analyzed.
      The third measure of progress is the expected number of clone islands generated;
      an island covers successive intervals. Finally, using these measures of progress,
      we compare the efficiency of this new mapping strategy with conventional clone
      mapping strategies.

PMID- 1992163
TI  - Preparing well-oriented sols of straight bacterial flagellar filaments for X-ray
      fiber diffraction.
AB  - Well-oriented sols of straight bacterial flagellar filaments have been obtained
      by preparing reconstituted flagellar filaments with an appropriate length
      distribution and choosing appropriate solvent conditions. An average filament
      length of 300 to 500 nm and the use of solvents with very low concentrations of
      salt has allowed us to prepare highly fluid sols that make flow orientation
      possible. X-ray fiber diffraction from these sols has shown distinct layer-line
      reflections to 3.5 A resolution in the meridional direction. Layer-line
      intensities have been collected by the angular deconvolution method up to 5 A
      resolution. The possibility of using a magnetic field to further improve the
      orientation has been explored and a solvent condition that makes flagellar sols
      sensitive to the magnetic field has been found. General applicability of the
      method to other systems is also discussed.

PMID- 1992164
TI  - Allosteric transition in triply met-haemoglobin.
AB  - Methaemoglobin undergoes a transition to a T-like form at acid pH in the presence
      of strong effectors such as inositol hexakisphosphate (IHP), as evidenced by
      spectroscopic and oxidation potential measurements. Since oxygen and CO do not
      bind to the ferric haems, it is difficult to compare the properties of the R-met
      and T-met forms with those of ferrous haemoglobin. We have therefore prepared 90%
      oxidized samples, where the dominant signal for ligand (oxygen or CO) binding is
      due to tetramers with three met haems. Measurements were made of the oxygen
      equilibrium curves and CO rebinding kinetics after photodissociation. Without
      effectors, the partially oxidized samples show mainly R-state properties.
      Addition of IHP at acid pH induces an increase in T-state behaviour, as indicated
      by a lower oxygen affinity and a higher fraction of the slow bimolecular
      component for CO rebinding.

PMID- 1992165
TI  - Assembly of Octopus dofleini hemocyanin. A study of the kinetics by
      sedimentation, light scattering and electron microscopy.
AB  - The kinetics of association of Octopus dofleini hemocyanin subunits to form the
      native decameric molecule have been studied with a combination of sedimentation,
      light scattering and electron microscopy. The reaction, initiated by addition of
      magnesium, is relatively slow, requiring hours to reach completion, with monomer
      and decamer as predominant molecular species throughout. Analysis of the light
      scattering data, including stopped-flow studies, reveals an initial lag period in
      the reaction, followed by a second-order process that is rate limiting. The lag
      period depends on both protein and magnesium ion concentration. Electron
      microscope studies reveal intermediates in the process, and support a model of
      assembly in which nucleation begins at the dimer level. Theoretical models for
      the process are compared.

PMID- 1992166
TI  - Structure of rubredoxin from Desulfovibrio vulgaris at 1.5 A resolution.
AB  - The X-ray model of rubredoxin from Desulfovibrio vulgaris has been refined
      against 1.5 A X-ray diffraction data collected on a diffractometer. The final
      model comprises 395 non-hydrogen protein atoms, and 180 solvent O atoms. The
      final R-value for the model with calculated H atom positions included as fixed
      contributions is 0.098 over all reflections greater than 2 sigma I from infinity
      to 1.5 A. The error in co-ordinates is estimated to be 0.08 A. The solvent model
      was twice redetermined during the later stages of refinement and was instrumental
      in its success. One sequence error has been detected and corrected (Thr21---
      Asp). The iron-sulfur site bond angles are distorted from true tetrahedral
      symmetry, as found in other rubredoxin structures. A significant deviation from
      tetrahedral angles is seen at C alpha atoms 9, 10, 42 and 43, interior angles of
      the loops binding the iron atom. The planes of two aromatic groups, Tyr4 and
      Trp37, are nearly parallel to, and lie under, an extended system of atoms that
      includes the peptide bonds preceding the first cysteine residue of each cysteine
      loop as well as the cysteine side-chain, the iron, and the cysteine side-chain of
      the opposite loop, forming a previously unrecognized extended system that may
      function in electron transfer.

PMID- 1992167
TI  - Refined crystal structures of subtilisin novo in complex with wild-type and two
      mutant eglins. Comparison with other serine proteinase inhibitor complexes.
AB  - The crystal structures of the complexes formed between subtilisin Novo and three
      inhibitors, eglin c, Arg45-eglin c and Lys53-eglin c have been determined using
      molecular replacement and difference Fourier techniques and refined at 2.4 A, 2.1
      A, and 2.4 A resolution, respectively. The mutants Arg45-eglin c and Lys53-eglin
      c were constructed by site-directed mutagenesis in order to investigate the
      inhibitory specificity and stability of eglin c. Arg45-eglin became a potent
      trypsin inhibitor, in contrast to native eglin, which is an elastase inhibitor.
      This specificity change was rationalized by comparing the structures of Arg45
      eglin and basic pancreatic trypsin inhibitor and their interactions with trypsin.
      The residue Arg53, which participates in a complex network of hydrogen bonds
      formed between the core and the binding loop of eglin c, was replaced with the
      shorter basic amino acid lysine in the mutant Lys53-eglin. Two hydrogen bonds
      with Thr44, located in the binding loop, can no longer be formed but are
      partially restored by a water molecule bound in the vicinity of Lys53. Eglin c in
      complexes with both subtilisin Novo and subtilisin Carlsberg was crystallized in
      two different space groups. Comparison of the complexes showed a rigid body
      rotation for the eglin c core of 11.5 degrees with respect to the enzyme,
      probably caused by different intermolecular contacts in both crystal forms.

PMID- 1992168
TI  - Prediction of protein side-chain conformation by packing optimization.
AB  - We have developed a rapid and completely automatic method for prediction of
      protein side-chain conformation, applying the simulated annealing algorithm to
      optimization of side-chain packing (van der Waals) interactions. The method
      directly attacks the combinatorial problem of simultaneously predicting many
      residues' conformation, solving in 8 to 12 hours problems for which the
      systematic search would require over 10(300) central processing unit years. Over
      a test set of nine proteins ranging in size from 46 to 323 residues, the
      program's predictions for side-chain atoms had a root-mean-square (r.m.s.)
      deviation of 1.77 A overall versus the native structures. More importantly, the
      predictions for core residues were especially accurate, with an r.m.s. value of
      1.25 A overall: 80 to 90% of the large hydrophobic side-chains dominating the
      internal core were correctly predicted, versus 30 to 40% for most current
      methods. The predictions' main errors were in surface residues poorly constrained
      by packing and small residues with greater steric freedom and hydrogen bonding
      interactions, which were not included in the program's potential function. van
      der Waals interactions appear to be the supreme determinant of the arrangement of
      side-chains in the core, enforcing a unique allowed packing that in every case so
      far examined matches the native structure.

PMID- 1992169
TI  - Is the hydrophobic effect stabilizing or destabilizing in proteins? The
      contribution of disulphide bonds to protein stability.
AB  - It has been recently concluded that the hydrophobic effect, hitherto regarded as
      a major driving force in the folding of proteins, destabilizes the folded state
      relative to the unfolded state. We summarize the properties of the hydrophobic
      effect obtained from solvent transfer experiments and show that the recent
      conclusion is an artifact of crosslinking in the unfolded state, caused by
      disulphide bonds, metals or cofactors. We show that, for the proteins in the data
      set, crosslinks surprisingly destabilize folded structures entropically, but
      stabilize them enthalpically to a greater extent. We also calculate non-polar
      surface areas of these unfolded proteins. These surface areas are decreased by
      crosslinks. The unfolded state of proteins lacking constraints, such as
      myoglobin, is well approximated by a mixture of residues containing alpha-helical
      and beta-sheet dihedral angles. Surface areas of unfolded proteins cannot be
      obtained by summing the surface areas of individual residues, since this ignores
      any unavoidable side-chain-side-chain interactions.

PMID- 1992170
TI  - Fifth week of Desert Storm fighting brings new challenges for medicine.

PMID- 1992171
TI  - Medicine and war: recognizing common vulnerability of friend and foe.

PMID- 1992173
TI  - Will more donor questions make blood safer?

PMID- 1992172
TI  - Public pressure ends 'bundled' drug program, but how much cost will drop remains
      unclear.

PMID- 1992174
TI  - New editor named at New England Journal.

PMID- 1992175
TI  - Pharmaceutical industry commission, government agencies seek to expedite new
      addiction therapy.

PMID- 1992177
TI  - From the Centers for Disease Control. Change of dosing regimen for malaria
      prophylaxis with mefloquine.

PMID- 1992176
TI  - From the Centers for Disease Control. Mortality attributable to HIV
      infection/AIDS--United States, 1981-1990.

PMID- 1992178
TI  - A piece of my mind. A dream.

PMID- 1992179
TI  - The order of authorship.

PMID- 1992180
TI  - The utility of CPR in elderly persons.

PMID- 1992182
TI  - Transcervical balloon tuboplasty (and which end is distal?)

PMID- 1992181
TI  - RU-486: Hoechst-Roussel (US), Hoechst AG, Roussel Uclaf SA, and Hoechst-Roussel
      Pharmaceuticals Inc.

PMID- 1992183
TI  - Zinc supplementation and anemia.

PMID- 1992184
TI  - Trends in alcohol consumption by pregnant women. 1985 through 1988.
AB  - To examine trends in alcohol consumption among pregnant women, we examined data
      collected from 21 states participating in the Behavioral Risk Factor Surveillance
      System for 4 consecutive years: 1985 through 1988. Overall, 429 (25%) of 1712
      pregnant women and 19,903 (55%) of 36,057 nonpregnant women 18 to 45 years of age
      reported using alcohol in the previous month. Pregnant women who used any alcohol
      reported consuming a median of four drinks per month, whereas nonpregnant women
      who used any alcohol reported nine. The prevalence of alcohol consumption among
      pregnant women declined steadily, from 32% in 1985 to 20% in 1988, but the median
      number of drinks per month for pregnant women who drank did not change. No
      decline was observed among the less educated or those under the age of 25 years.
      In 1988, the prevalence of alcohol use among pregnant women remained highest
      among smokers (37%) and the unmarried (28%). Although the overall consumption of
      alcohol by pregnant women in the United States appears to be declining, special
      efforts are needed to reduce alcohol use among pregnant women who are smokers,
      unmarried, less educated, or younger, women who may already be at high risk of a
      poor pregnancy outcome.

PMID- 1992185
TI  - Creutzfeldt-Jakob disease in pituitary growth hormone recipients in the United
      States.
AB  - To assess the magnitude of Creutzfeldt-Jakob disease (CJD) occurrence among
      recipients of pituitary-derived human growth hormone (HGH), we conducted an
      epidemiologic follow-up of 6284 recipients of HGH distributed through the
      National Hormone and Pituitary Program. Seven neuropathologically confirmed cases
      of CJD have occurred in this population to date: six patients with clinical CJD
      presented with ataxia and imbalance, rather than with altered mentation, which is
      the most common initial manifestation in sporadic CJD, and one patient died in
      the preclinical incubation state of the disease. All seven cases occurred among
      the nearly 700 HGH recipients who started therapy before 1970. Since only 10% of
      the cohort has been followed up for the 15-year average incubation interval from
      midpoint of HGH treatment to onset of symptoms, the great majority of potentially
      exposed patients have not yet attained the requisite incubation period for
      expression of CJD. The median duration of HGH therapy of 100 months in the CJD
      cases was significantly longer than 41 months for all patients starting treatment
      before 1970; thus, the duration of pituitary HGH therapy is a major risk factor
      for CJD.

PMID- 1992186
TI  - Treatable abdominal pathologic conditions and unsuspected malignant neoplasms at
      autopsy in veterans who received mechanical ventilation.
AB  - STUDY OBJECTIVE: To determine, in medical patients who received mechanical
      ventilation, the frequency and types of major unexpected diagnoses at autopsy
      that, if known before death, would probably have led to improved survival (class
      I errors) or substantively changed management but not survival (class IIB
      errors). DESIGN: Retrospective cohort study. SETTING: Six medical intensive care
      units in a Department of Veterans Affairs Cooperative Study. PATIENTS: One
      hundred seventy-two autopsied patients of the 401 veterans who received
      mechanical ventilation and died in the hospital. RESULTS: The class I error rate
      was 12%. Abdominal pathologic conditions--abscesses, bowel perforations, or
      infarction--were as frequent as pulmonary emboli as a cause of class I errors.
      While patients with abdominal pathologic conditions generally complained of
      abdominal pain, results of examination of the abdomen were considered
      unremarkable in most patients, and the symptom was not pursued. Six percent of
      patients had extensive malignant neoplasms (class IIB errors). CONCLUSIONS:
      Atypical presentation of potentially treatable abdominal pathologic conditions is
      a common cause of class I errors in veterans who receive mechanical ventilation.
      Conversely, several patients with unrecognized terminal conditions underwent
      intensive intervention. If the information gained at autopsy had been known
      before death, management would have probably changed substantively in 18% of
      patients.

PMID- 1992188
TI  - The Orphan Drug Act. The first 7 years.
AB  - The 1983 Orphan Drug Act sought to increase market incentives and decrease
      regulatory barriers for products used to treat rare ("orphan") diseases. Major
      provisions included market exclusivity, tax credits, and regulatory process
      clarifications. This analysis compares pre- and post-Act industry and government
      data to examine changes associated with the law. While industry sponsored 34
      marketed and 24 experimental orphan drugs in the 17 years prior to the Act, it
      has sponsored 39 of 42 marketed orphan products in the 7 years since the Act. An
      additional 301 experimental products have orphan designation. While 25 of 40
      marketed orphan products reportedly had annual sales of less than $1 million,
      product sales for three conditions are more than $100 million annually. This
      prompted changes in the law, passed by Congress in 1990, but vetoed. Overall, the
      law has been associated with an increase in orphan product development. The law's
      costs and benefits to companies, patients, and the public should be examined if
      future changes are proposed.

PMID- 1992187
TI  - Somatostatin analogue, octreotide, reduces increased glomerular filtration rate
      and kidney size in insulin-dependent diabetes.
AB  - To determine whether treatment with a somatostatin analogue can reduce kidney
      hyperfiltration and hypertrophy in insulin-dependent diabetes mellitus, we
      studied 11 patients with insulin-dependent diabetes mellitus and glomerular
      hyperfiltration. The patients were assigned randomly to receive continuous
      subcutaneous infusion of either octreotide, 300 micrograms/24 h (five patients)
      or placebo (six patients) for 12 weeks. At baseline, mean glomerular filtration
      rate and mean total kidney volume were not significantly different in the two
      groups. However, after 12 weeks of treatment, the mean glomerular filtration rate
      was significantly lower in the octreotide group (136 mL/min per 1.73 m2; range,
      91 to 158 mL/min per 1.73 m2) than in the placebo group (157 mL/min per 1.73 m2;
      range, 138 to 184 mL/min per 1.73 m2). Furthermore, the mean total kidney volume
      was significantly lower after treatment in the octreotide group (379 mL/1.73 m2;
      range, 307 to 454 mL/1.73 m2) than in the placebo group (389 mL/1.73 m2; range,
      347 to 465 mL/1.73 m2). Glycemic control did not change significantly in either
      group. We conclude that subcutaneous infusion of octreotide for 12 weeks reduces
      increased glomerular filtration rate and kidney size in patients with insulin
      dependent diabetes mellitus despite the fact that glycemic control remains
      unchanged.

PMID- 1992189
TI  - The prevalence of gallstone disease in very old institutionalized persons.
AB  - We present the results of a study that was undertaken at a large geriatric
      nursing home to assess the prevalence of gallstone disease in very old
      institutionalized persons. One hundred seventeen residents underwent ultrasound
      examination of the gallbladder. Two thirds of 82 women and half of 35 men had
      gallstone disease. When stratified for age, 80% of women and men over the age of
      90 years were positive for the disease. In summary, the prevalence of gallstone
      disease in our very old nursing home population was found to be unexpectedly
      high.

PMID- 1992190
TI  - The familial hyperchylomicronemia syndrome. New insights into underlying genetic
      defects.

PMID- 1992191
TI  - Estrogen in yams.

PMID- 1992192
TI  - Traumatic split nail dystrophy.

PMID- 1992193
TI  - Medical educators' views on medical education reform.
AB  - To determine whether medical educators perceive a need for change in medical
      student education, we analyzed data from a 1989 survey of 1369 respondents from
      all US schools of allopathic medicine. Except for basic sciences faculty, a
      majority of educators stated that "fundamental changes" are needed in medical
      student education in the United States. Nearly three fourths of deans and
      associated deans reported the need for "fundamental changes" or "thorough
      reform." At least 79% of educators voiced support for six specific reforms, such
      as rewarding teaching excellence and increasing clinical education in ambulatory
      and community settings. While slight majorities supported reducing class size and
      centralizing governance, substantial proportions stated that they would "work
      against" such reforms. Most educators reported that a broad base of support
      within the school would be essential for change. The survey suggests a
      restlessness among the leaders of medical education.

PMID- 1992194
TI  - Thomas Hodgkin and Hodgkin's disease. Two paradigms appropriate to medicine
      today.
AB  - Thomas Hodgkin was an investigator whose contributions extended over a wide range
      of medicine. While he is known for Hodgkin's disease, this was not his major
      interest. That this is so has more to do with his successors than him. He had a
      highly committed social conscience and was outspoken in advocacy of his
      positions. This greatly limited his professional career. The history of Hodgkin's
      disease is one of hypothesis generation, which allowed for its effective
      treatment even without an understanding of its etiology, illustrating the
      approximate nature of scientific discovery and the importance of chance in
      historical attribution. Hodgkin, as a scientist, healer, and socially committed
      individual, embodied the many characteristics that are desirable for today's
      physician, while the evolution of knowledge about Hodgkin's disease and its
      treatment is an instructive model for future medical advances.

PMID- 1992195
TI  - The management of primary pulmonary hypertension.
AB  - Primary pulmonary hypertension is a clinical syndrome characterized by pulmonary
      hypertension in the absence of sufficient underlying cardiac, parenchymal
      pulmonary, or systemic disease to account for it. The population of patients with
      primary pulmonary hypertension is a heterogeneous one, both clinically and
      histologically. As the etiologic mechanisms are unknown, therapy is directed
      toward the consequences of the pulmonary vascular process. Oxygen
      supplementation, the use of digoxin and diuretics for symptomatic heart failure,
      and anticoagulation all may have a role in treating primary pulmonary
      hypertension, although vasodilator therapy has been the main area of
      investigation. Screening for vasodilator responsiveness, defining a favorable
      vasodilator effect, predicting long-term effectiveness, and deciding who to treat
      have all been controversial. New approaches, such as use of high-dose calcium
      channel-blocking agents and continuous intravenous infusion of prostacyclin (an
      investigational agent), have recently been proposed. When medical therapies are
      exhausted, heart-lung or lung transplantation has increasingly become an option
      for selected patients.

PMID- 1992196
TI  - Nosocomial bacteremia and drug theft. Epidemiology finds the solution.

PMID- 1992197
TI  - New pathways for medical education.

PMID- 1992198
TI  - Tired of taking the blame, AIDS drug regulator Ellen Cooper quits.

PMID- 1992199
TI  - Spector of ground war overshadows Desert Storm medical, peace efforts.

PMID- 1992200
TI  - New ultrasound evidence appears to link prenatal brain damage, cerebral palsy.

PMID- 1992201
TI  - Clinical data release: how soon?

PMID- 1992202
TI  - From the Centers for Disease Control. Rotavirus surveillance--United States, 1989
      1990.

PMID- 1992203
TI  - From the Centers for Disease Control. Reye syndrome surveillance--United States,
      1989.

PMID- 1992204
TI  - A piece of my mind. Skeptical of skeptics.

PMID- 1992205
TI  - Medicaid eligibility, prenatal care, and the outcome of pregnancy.

PMID- 1992206
TI  - HIV and HTLV in Africa.

PMID- 1992207
TI  - Women in academic medicine.

PMID- 1992208
TI  - Now hear this, slacker gome doctors: anal-retentive gunner shoots down pass/fail.

PMID- 1992209
TI  - Resident work hours and the American Board of Medical Specialties.

PMID- 1992210
TI  - APACHE scores.

PMID- 1992211
TI  - Nosocomial Pseudomonas pickettii bacteremias traced to narcotic tampering. A case
      for selective drug screening of health care personnel.
AB  - Three patients in a university hospital developed nosocomial infusion-related
      Pseudomonas pickettii bacteremia. Investigation identified six additional
      patients who had received intravenous fluid contaminated by P pickettii but did
      not become ill. All nine patients had had surgery, and each of these patients but
      only nine of 19 operated-on control patients had received intravenous fentanyl
      citrate in the operating room; the mean dose given to the nine case patients was
      far greater than that given to control patients. Fentanyl in 20 (40%) of 50
      predrawn 30-mL syringes was shown to be contaminated by P pickettii.
      Contamination was caused by theft of fentanyl from predrawn synringes and
      replacement by distilled water contaminated by P pickettii. Narcotic theft by
      health care personnel may cause patients to suffer pain needlessly and can also
      result in dire unanticipated consequences, such as nosocomial bacteremia. Whereas
      drug testing in the workplace is highly controversial, we believe that testing of
      health care personnel is indicated when drug abuse or theft is suspected.

PMID- 1992212
TI  - Protective efficacy of Haemophilus influenzae type b polysaccharide and conjugate
      vaccines in children 18 months of age and older.
AB  - To evaluate the protective efficacy of polyribosylribitol phosphate (PRP) and
      polyribosylribitol phosphate-diphtheria toxoid (PRP-D) vaccines in children 18 to
      59 months of age, we conducted a case-control study in Los Angeles (Calif) County
      between July 1, 1988, and July 31, 1989. Seventy-nine children with invasive
      Haemophilus influenzae type b disease 18 to 59 months of age were identified, and
      212 controls were selected by random-digit telephone dialing methods. Cases and
      controls were stratified by age and month of disease onset of the case. Seventeen
      PRP vaccine failures and two PRP-D vaccine failures occurred more than 2 weeks
      after vaccination. The PRP vaccine was shown not to be effective (point estimate-
      47%; 95% confidence interval,--307% to 47%), but the PRP-D vaccine was 88%
      protective (95% confidence interval, 42% to 97%). Adjustment of the efficacy
      estimates for potential confounding variables did not change the results
      significantly. The PRP-D vaccine provided significantly better protection than
      the PRP vaccine against invasive H influenzae type b disease in this population.

PMID- 1992213
TI  - Depression and mortality in nursing homes.
AB  - To determine the prevalence rates of major depressive disorder and of depressive
      symptoms and their relationship to mortality in nursing homes, research
      psychiatrists examined 454 consecutive new admissions and followed them up
      longitudinally for 1 year. Major depressive disorder occurred in 12.6% and 18.1%
      had depressive symptoms; the majority of cases were unrecognized by nursing home
      physicians and were untreated. Major depressive disorder, but not depressive
      symptoms, was a risk factor for mortality over 1 year independent of selected
      physical health measures and increased the likelihood of death by 59%. Because
      depression is a prevalent and treatable condition associated with increased
      mortality, recognition and treatment in nursing homes is imperative.

PMID- 1992214
TI  - Lovastatin efficacy in reducing low-density lipoprotein cholesterol levels on
      high- vs low-fat diets.
AB  - The effectiveness of lovastatin was compared with both a high-fat vs low-fat
      diet. Hypercholesterolemic subjects were studied under metabolic ward conditions
      for diet periods of 3 weeks while receiving lovastatin (40 mg/d) or placebo.
      Multiple lipoprotein levels were measured during the final week of each diet
      period. Nineteen subjects completed the study on the high-fat (43% of kilojoules)
      diet and 16 on the low-fat (25% of kilojoules) diet. Lovastatin reduced total
      cholesterol by 23% and low-density lipoprotein cholesterol by 30%, compared with
      placebo on both diets, with no significant diet-drug interaction. High-density
      lipoprotein cholesterol was raised by 7% to 8% on the diet regimens. Addition of
      lovastatin to the low-fat diet permitted 80% of subjects on this diet, but less
      than 50% of those on the high-fat diet, to achieve current guidelines. Although
      lovastatin produces a comparable percentage reduction in lipoprotein profiles on
      either diet, the accompanying low-fat diet remains advisable for additional
      reduction of low-density lipoprotein cholesterol levels to specified goals.

PMID- 1992216
TI  - Comparison of characteristics of esophageal squamous cell carcinoma associated
      with head and neck cancer and those with gastric cancer.
AB  - In ongoing reviews of 339 patients with surgically treated primary squamous cell
      carcinoma, there were 19 (5.6%) with concurrent gastric cancer and 11 (3.2%) with
      head and neck cancer. The incidences of intra-esophageal multiple occurrence of
      esophageal cancer are 27.3% and 26.3% in those with associated head and neck
      cancer and gastric cancer, respectively, and higher than 7.1% in those without
      such a concurrent cancer. There was no difference in the clinicopathological
      characteristics of those with concurrent head and neck and gastric cancers,
      except for the higher incidence of metachronous occurrence in the former. These
      findings suggest that, in cases of esophageal cancer associated with concurrent
      head and neck cancer and gastric cancer, intraesophageal multiplicity of the
      esophageal carcinoma is frequent and that preoperative serial evaluations is most
      important to design treatment and estimate the prognosis.

PMID- 1992215
TI  - Mucoepidermoid carcinoma of the salivary glands: a reappraisal of the influence
      of tumor differentiation on prognosis.
AB  - Thirty-nine cases of mucoepidermoid carcinoma of the salivary glands were
      reviewed for a reappraisal of the influence of the grade of differentiation on
      the outcome of the disease. The age of the patients ranged between 7 and 84
      years. Fifteen patients were females and 24 males. The tumors were located at the
      parotid gland (n = 30), the submaxillary gland (n = 1), the soft palate (n = 5)
      and the oral mucosa NOS (n = 3). At presentation 4 tumors were intraglandular and
      35 extraglandular; three patients had lymph node metastases and one patient lung
      metastases. The grade of differentiation was assessed using the criteria of
      Healey et al. Twelve tumors were classified as grade I, 17 as grade II, and 10 as
      grade III. Follow-up information was obtained with a duration of 5-144 months
      (mean 44.7 months). Six cases recurred locally and 5 developed metastases. Five
      years cumulative survival was 100% for grade I, 70.1% for grade II, and 47.2% for
      grade III. The results point to the usefulness of the assessment of the grade of
      differentiation as a guide to anticipate the outcome of the disease.

PMID- 1992217
TI  - Immune competent cells of regional lymph nodes in colorectal cancer patients: I.
      Flow cytometric analysis of lymphocyte subpopulation.
AB  - Lymphocyte subpopulations of the regional lymph nodes in 20 colorectal cancer
      patients were measured by flow cytometry to analyze nodal lymphocytes
      phenotypically. Eleven patients with cholelithiasis were used as controls.
      Comparison of lymphocyte subpopulations between colorectal cancer and control
      groups revealed a significantly increased rate of Leu-12+ cells in the cancer
      patients. Furthermore, a significant increase of Leu-3a+ Leu-8- cells and a
      significant decrease of Leu-3a+ Leu-8+ cells were also found in the paracolic
      nodes of the cancer patients. However, Leu-2a+ Leu-15- cells were not different
      between the both groups. Meanwhile, in the cancer patients, the rates of Leu-4+,
      Leu-3a+, and Leu-3a+ Leu-8- cells were higher in the paracolic nodes compared
      with the intermediate nodes. Additional investigation of the correlation between
      clinicopathological features of the tumors and lymphocyte subpopulations, showed
      that Leu-12+ cells were related to the tumor size and Leu-2a+ 15- cells related
      to the histopathological type. The foregoing results indicate that the rates of
      both B and helper T cells, which may specifically participate in the antibody
      production, increase in the regional lymph nodes of colorectal cancer patients.

PMID- 1992218
TI  - Characterization and histopathological correlation of cytosol proteins of benign
      and malignant breast tumors.
AB  - Significant differences in cytosol protein level exist between normal/benign and
      cancerous breast tissues. There is a positive correlation between the cytosol
      protein level and histological grade of carcinoma. Well-differentiated carcinoma
      have a lower value of cytosol protein than poorly differentiated carcinoma. In
      slab gel electrophoregrams, the total numbers of bands are almost identical in
      normal, benign, and malignant conditions. In addition, 37 Kd protein band is
      consistently present in malignant cases and always absent in normal or benign
      cases. More extensive biophysical examination of this band may provide further
      insight into the protein alterations in cancer cells at the molecular level.

PMID- 1992219
TI  - Surgical resection of a solitary liver metastasis in a 46-year-old patient with a
      malignant thymoma.
AB  - Clinical history, surgical treatment, and pathologic findings of a solitary liver
      metastasis of a malignant thymoma in a 46-year-old female are reported. An
      extensive literature review has revealed no record of surgical resection of liver
      metastasis in a patient with invasive thymoma.

PMID- 1992220
TI  - Lactation following conservation surgery and radiotherapy for breast cancer.
AB  - A 38-year-old woman with early stage invasive breast cancer was treated with wide
      excision of the tumor, axillary lymph node dissection, and breast irradiation.
      Three years later, she gave birth to a normal baby. She attempted breast feeding
      and had full lactation from the untreated breast. The irradiated breast underwent
      only minor changes during pregnancy and postpartum but produced small amounts of
      colostrum and milk for 2 weeks postpartum. There are only a few reports of
      lactation after breast irradiation. These cases are reviewed, and possible
      factors affecting breast function after radiotherapy are discussed. Because of
      scant information available regarding its safety for the infant, nursing from the
      irradiated breast is not recommended.

PMID- 1992221
TI  - Expression of HLA-DR and secretory component antigens and lymphocyte infiltration
      in human gastric nonmalignant and malignant tissues: an immunohistochemical
      study.
AB  - The relation between HLA-DR and secretory component (SC) expression and the
      degree of lymphocyte infiltration was immunohistochemically examined in human
      gastric mucosa with or without intestinal metaplasia and gastric carcinoma
      tissues. Gastric mucosa without obvious inflammation showed neither expression of
      HLA-DR or SC nor remarkable lymphoid infiltration. In contrast, gastric mucosa
      with chronic inflammation, tissues with incomplete type of intestinal metaplasia,
      and carcinoma demonstrated both HLA-DR and SC in almost the same area and also
      prominent lymphoid infiltration in the surrounding stroma. This simultaneous
      expression of HLA-DR and SC was not observed in complete type of intestinal
      metaplasia. The results indicate a close relationship between expression of HLA
      DR and SC and the presence of lymphocyte infiltration in gastric mucosa, areas of
      incomplete type of intestinal metaplasia and in gastric carcinomas.

PMID- 1992222
TI  - Histologic and immunohistologic diversity of non-Hodgkin's lymphoma of lymph node
      origin.
AB  - To examine whether nodal non-Hodgkin's lymphomas (NHL) share common features in
      every nodal site, histologic and immunohistologic findings were analyzed site by
      site. Cases selected were nodal NHL of neck (17 cases), submandibular (10 cases),
      inguinal (9 cases), and abdominal cavity (22 cases). No significant differences
      in age distribution were found. A slight female preponderance was present in
      cases with inguinal NHL. Histologic and immunohistologic findings showed that
      nodal NHL were heterogeneous; (1) T-cell type was frequent in the neck but
      exceptional in other sites, (2) frequency of high-grade tumors was much higher in
      the intra-abdominal cavity but low in other sites, and (3) follicular lymphoma
      was common in the submandibular and inguinal regions. Previous studies indicated
      that histologic and/or immunologic types of NHL correlated with pathogenesis of
      lymphoma; EB virus and HTLV-1 for B and T lymphomagenesis, respectively, and
      acquired immunodeficiency syndrome (AIDS) for development of high-grade tumors.
      The present results may provide an insight to consider as a possible pathogenesis
      of NHL.

PMID- 1992223
TI  - Clinical management of gastric cancer and concomitant esophagogastric varices.
AB  - We report the late results of treatment of 13 consecutive patients with gastric
      cancer and concomitant esophagogastric varices. Of seven good-risk patients
      classified as Child's class A or B, gastrectomy together with selective shunt
      operation was performed in two, total gastrectomy with splenectomy in three, and
      distal partial gastrectomy with paraesophageal devascularization without
      splenectomy in one. The remaining patient with early gastric cancer underwent
      distal partial gastrectomy following repeated endoscopic injection sclerotherapy
      (EIS) for treatment of the esophageal varices. Although the majority of patients
      who underwent surgical repair of varices (i.e., shunt, splenectomy, or
      devascularization) died, total gastrectomy with splenectomy was the only
      procedure that led to control of the esophageal varices. Since partial
      gastrectomy combined with EIS limits the morbidity and mortality of an extensive
      resection and at the same time controls esophageal variceal bleeding, it is
      probably the procedure of choice for patients with a carcinoma in the lower two
      thirds of the stomach. Concerning non-surgical cases, two patients were
      effectively treated using laser endoscopy and EIS, without the occurrence of
      variceal bleeding. The remaining four patients, given chemotherapy or irradiation
      for treatment of gastric carcinoma, died within 4 months with variceal bleeding
      or liver failure. For the poor-risk patients with evidence of severe liver
      dysfunction, laser treatment and EIS would be the treatment of choice.

PMID- 1992224
TI  - Abstracts, 20th annual meetings. Keystone Symposia on Molecular and Cellular
      Biology. Gene expression in neuromuscular development. January 24-30, 1991.

PMID- 1992225
TI  - Abstracts, 20th annual meetings. Keystone Symposia on Molecular and Cellular
      Biology. Molecular basis of oxidative damage by leukocytes. January 28-February
      3, 1991.

PMID- 1992226
TI  - Abstracts, 20th annual meetings. Keystone Symposia on Molecular and Cellular
      Biology. Molecular mechanisms of vascular diseases. January 24-30, 1991.

PMID- 1992228
TI  - Abstracts, 20th annual meetings. Keystone Symposia on Molecular and Cellular
      Biology. Translational control. February 22-March 1, 1991.

PMID- 1992227
TI  - Abstracts, 20th annual meetings. Keystone Symposia on Molecular and Cellular
      Biology. Gene regulation by antisense RNA and DNA. February 2-7, 1991.

PMID- 1992229
TI  - Abstracts, 20th annual meetings. Keystone Symposia on Molecular and Cellular
      Biology. Genomic instability and cancer. February 4-10, 1991.

PMID- 1992230
TI  - The anatomy of peer review.

PMID- 1992231
TI  - Coronary artery bypass grafting in elderly patients. Comparative results in a
      consecutive series of 469 patients older than 75 years.
AB  - A consecutive series of 7104 patients undergoing isolated coronary artery bypass
      grafting during an 18-year period (1971 to 1988) included 469 patients older than
      75 years. Results were analyzed to determine comparative risk factors for
      morbidity, early and late survival, and functional outcome. Patients younger than
      75 years (group I) and patients older than 75 years (group II) were identical for
      ejection fraction and standard hemodynamic indices. Mean number of grafts and
      crossclamp time were greater for group II patients (p less than 0.01). Mean age
      of group I was 58.6 years and group II, 77.6 years (p less than 0.01). Women
      composed 19.7% (1308/6635) of group I and 36.2% (170/469) of group II patients (p
      less than 0.05). Mammary grafts were placed in 57.7% (3830/6635) of group I and
      41.6% (195/469) of group II patients (p less than 0.05). Overall perioperative
      mortality rate was 2.1% for group I and 6.8% for group II (p less than 0.05).
      Perioperative myocardial infarction rate was similar for the two groups.
      Ventricular and supraventricular arrhythmias, renal insufficiency, neurologic
      complications, prolonged ventilatory support, increased hospital cost, and
      prolonged hospitalization were significantly more prevalent (all p less than
      0.05) in patients older than 75 years. Five and 10 years postoperatively, there
      were no significant differences between groups I and II with regard to event-free
      status including angina, myocardial infarction, and reoperation. The 5-year
      survival rate was 92% for group I and 80% for group II (p less than 0.05),
      similar to that of age-matched control subjects. The significantly increased
      potential for complications and expense of coronary bypass in patients over 75
      years of age mandates judicious patient selection and preoperative counseling.
      Despite a significantly increased early mortality and an anticipated decreased
      long-term survival paralleling normal life table survival curves, good
      intermediate functional improvement can be realized in patients older than 75
      years, comparable with that expected in a much younger age group.

PMID- 1992232
TI  - Meralgia paresthetica after coronary bypass surgery.
AB  - Meralgia paresthetica is a neurologic disorder characterized by localized
      paresthesia and numbness on the anterolateral aspect of the thigh and involving
      the lateral femoral cutaneous nerve. It involves no motor deficits. Meralgia
      paresthetica, which may result from a variety of causes, has been observed as a
      rare complication in heart operations. Its cause when associated with such
      operations is uncertain but may be prolonged relaxed positioning on the operating
      table and recovery room stretcher. Another possible cause of meralgia
      paresthetica after heart operations is the "frog-leg" position of the legs during
      vein harvesting. Patients with this condition should be advised of its
      untreatable, but benign and self-limiting, nature.

PMID- 1992233
TI  - Changes in lymphocyte subpopulations as a result of cardiopulmonary bypass. The
      effect of blood transfusion.
AB  - Cardiopulmonary bypass is associated with postoperative humoral and cellular
      immune changes. Postoperative decrease in T helper (CD4), T suppressor (CD8), and
      B lymphocyte counts; decrease or reversal of the CD4/CD8 ratio; and poor in vitro
      response to mitogens have also been observed. Similar changes in lymphocyte
      number and function have also been noted in patients receiving transfusions. To
      determine whether observed changes after cardiopulmonary bypass are related to
      the bypass itself or to associated blood transfusions, we conducted a study of
      lymphocyte subsets in transfused and nontransfused patients. A flow cytometric
      analysis of seven lymphocyte subpopulations was conducted in 18 patients
      undergoing bypass, eight of whom did not receive a transfusion. The transfused
      group comprised recipients of both homologous (n = 8) and autologous (n = 2)
      blood. Total lymphocytes and lymphocytes with markers for CD3 (pan-T cells), CD4,
      and CD8 decreased significantly postoperatively independent of transfusion. B
      lymphocytes decreased postoperatively in both the autologous transfusion and no
      transfusion groups. However, this trend was not seen in patients receiving
      homologous blood, and three of these patients had evidence of T cell activation,
      suggestive of an immune response to homologous transfusion. Bypass produces
      significant changes in selected lymphocyte subsets. Furthermore, simultaneous
      homologous blood transfusion may specifically elicit an immune response in some
      patients undergoing cardiopulmonary bypass.

PMID- 1992234
TI  - Left ventricular mechanics of ejecting, postischemic hearts during left
      ventricular circulatory assistance.
AB  - We measured the effects of left ventricular circulatory assistance on ventricular
      mechanics of ejecting sheep hearts before and after global ischemia. Flows from
      left atrium to femoral artery ranged between 20 and 100 ml/kg/min during
      circulatory assistance. In preischemic, ejecting hearts increasing flow through
      the left ventricular assist device progressively decreased stroke volume, end
      diastolic volume, and circumferential systolic wall stress, but only slightly
      decreased end-systolic volume. In postischemic, ejecting hearts left ventricular
      assistance progressively and substantially decreased both end-diastolic volume
      and end-systolic volume; at high flows, end-systolic volume returned to the
      normal range of preischemic hearts. High flows through the assist device also
      shifted end-systolic points of pressure-volume loops leftward and increased the
      stroke work/end-diastolic volume ratio in ejecting postischemic hearts; these
      observations raise the possibility that left ventricular circulatory assistance
      acutely improves myocardial contractility of postischemic hearts.

PMID- 1992235
TI  - Evolution of human cardiac myocyte dimension during prolonged mechanical support.
AB  - In animal models using left ventricular assist systems over long time periods,
      myocardial cellular atrophy has been reported, raising concern that prolonged
      clinical use of such systems might lead to deterioration in left ventricular
      function. At the University of Pittsburgh, long-term clinical use of the Novacor
      (Baxter Healthcare Corp., Novacor Div., Oakland, Calif.) left ventricular support
      system for patients awaiting heart transplants has allowed study of the effects
      of long-term mechanical support on human subjects. This study determined that
      cardiac myocyte dimension is initially greater in patients with end-stage cardiac
      disease who require support rather than in patients with the same disease who do
      not require such support. Although myocyte dimension does decrease within a few
      days of the inception of support, this decrease merely brings cell size closer to
      the values usual in patients with chronic end-stage cardiac disease, and no
      further shrinkage is observed. Thus the Novacor left ventricular assist system
      does not appear associated with left ventricular atrophy, and its long-term use
      may not be detrimental to left ventricular function.

PMID- 1992236
TI  - Beneficial effect of pericardial meshing on left ventricular pump performance in
      dogs.
AB  - To evaluate the effects of pericardial meshing (multiple incisions on the
      pericardium) on cardiac function, we examined left ventricular pump performance
      before and after pericardial meshing in six open chest dogs. We evaluated left
      ventricular systolic properties with the slope of end-systolic pressure-volume
      relation and diastolic properties with end-diastolic pressure-volume relation
      (chamber compliance). Overall left ventricular performance was assessed with end
      diastolic pressure versus cardiac output relation. Left ventricular chamber
      compliance was increased (31.3%) with pericardial meshing compared with direct
      closure of the pericardium, and cardiac output was increased (26.7%) for any
      given left ventricular end-diastolic pressure. The slope of the end-systolic
      pressure-volume relation was not altered in pericardial meshing. These results
      suggest that pericardial meshing improves left ventricular pump performance as a
      result of increasing left ventricular chamber compliance. This technique may
      benefit cardiac pump performance that is depressed by the direct closure of the
      pericardium after cardiac operations.

PMID- 1992237
TI  - Warm heart surgery.
AB  - Hypothermia is widely acknowledged to be the fundamental component of myocardial
      protection during cardiac operations. Although it prolongs the period of ischemic
      arrest by reducing oxygen demands, hypothermia is associated with a number of
      major disadvantages, including its detrimental effects on enzymatic function,
      energy generation, and cellular integrity. We hypothesized that the ideal
      protected state of the heart would be electromechanically arrested and perfused
      with blood, that is, aerobic arrest. Under these conditions the fundamental need
      for hypothermia becomes questionable. We have developed a novel approach to
      myocardial protection during cardiac operations based on these concepts, in which
      the chemically arrested heart is perfused continuously with blood and maintained
      at 37 degrees C. In 121 consecutive coronary bypass procedures we have compared
      this approach with a historical cohort of 133 consecutive patients treated with
      hypothermic cardioplegia. Perioperative myocardial infarction was significantly
      less prevalent (1.7% versus 6.8%; p less than 0.05) in the warm cardioplegic
      group, as was the use of the intraaortic balloon pump (0.9% versus 9.0%; p less
      than 0.005) and the prevalence of low output syndrome (13.5% versus 3.3%; p less
      than 0.005). Cardiac output immediately after bypass was significantly higher
      than before bypass (3.1 +/- 0.9 versus 4.9 +/- 1.0 L/min; p less than 0.001) only
      in the warm cardioplegia group. Furthermore, the heartbeat in 99.2% of patients
      treated with continuous warm cardioplegia converted to normal sinus rhythm
      spontaneously after removal of the aortic crossclamp compared with only 10.5% of
      the hypothermic group. The time from removal of the aortic crossclamp to
      discontinuation of cardiopulmonary bypass (i.e., reperfusion time) was
      significantly shorter in the warm cardioplegia group (11 +/- 4.3 versus 27 +/-
      5.6 minutes; p less than 0.001). Our results suggest that continuous normothermic
      blood cardioplegia is safe and effective. Conceptually, this represents a new
      approach to the problem of maintaining excellent myocardial preservation during
      cardiac operations.

PMID- 1992238
TI  - Overdose reperfusion of blood cardioplegic solution. A preventable cause of
      postischemic myocardial depression.
AB  - Reperfusion of warm blood cardioplegic solution is useful in minimizing
      reperfusion damage after ischemia. This study tests the hypothesis that
      overzealous administration of blood cardioplegic solution at reperfusion
      counteracts these benefits and can lead to a prevalence of depressed ventricular
      performance and mortality similar to that seen after normal blood reperfusion.
      Thirty-one dogs underwent 45 minutes of 37 degrees C global ischemia on vented
      bypass. Six received normal blood reperfusion and 25 were reperfused with a warm
      aspartate/glutamate-enriched blood cardioplegic solution; of these, eight
      received high-dose (3600 +/- 600 ml) and 17 received limited-dose (1180 +/- 120
      ml) blood cardioplegic reperfusion over 10 to 20 minutes. High-dose blood
      cardioplegic perfusion (5100 +/- 200 ml) without prior ischemia was tested in an
      additional five dogs. High-dose blood cardioplegia without preceding ischemia did
      not alter ventricular function (peak stroke work index 96% of control). After
      ischemia, normal blood reperfusion (no cardioplegia) resulted in marked left
      ventricular dysfunction (peak stroke work index 36% of control, p less than 0.05
      versus control) and a 33% mortality rate (2/6 died). High-dose cardioplegic
      reperfusion yielded marginal recovery of stroke work index (40% of control, p
      less than 0.05 versus control) and a 25% mortality rate (2/8 died). In contrast,
      limited-dose reperfusion of blood cardioplegic solution allowed 100% survival
      (17/17) and restored stroke work index to 90% of control (1.3 versus 1.45
      gm.m/kg). We conclude that reperfusion damage can be avoided by initial
      reoxygenation with limited doses of substrate-enriched blood cardioplegic
      solution. Conversely, high-dose reperfusion of blood cardioplegic solution
      offsets this benefit, reduces recovery substantially, and may be lethal.

PMID- 1992239
TI  - Studies of controlled reperfusion after ischemia. XIX. Reperfusate composition:
      benefits of blood cardioplegia over fluosol DA cardioplegia during regional
      reperfusion--importance of including blood components in the initial reperfusate.
AB  - HYPOTHESIS: Initial reoxygenation with blood cardioplegic solution produces
      better regional recovery than with Fluosol DA cardioplegic solution (Green Cross
      Corporation, Osaka, Japan) because blood cardioplegia ensures delivery of
      important blood components (i.e., plasma and red blood cells) that limit
      reperfusion damage. METHODS: Twenty-five dogs underwent 2 hours of ligation of
      the left anterior descending coronary artery followed by controlled reperfusion
      at 50 mm Hg through an internal mammary graft on total vented bypass. Five dogs
      received normal blood reperfusion, 10 dogs received a 20-minute reperfusion with
      Fluosol DA 20% cardioplegic solution, and 10 others received a blood cardioplegic
      reperfusate of identical composition (i.e., pH, calcium, potassium, glucose,
      osmolarity). Regional oxygen consumption was measured during reperfusion, and
      segmental shortening (ultrasonic crystals), tissue water content, and
      histochemical damage (triphenyltetrazolium chloride stain) were assessed 2 hours
      later. RESULTS: Reperfusion with normal blood failed to restore contractile
      function (3% systolic shortening), caused severe edema (81% water content), and
      caused marked histochemical damage (48% triphenyltetrazolium chloride
      nonstaining). Hearts reperfused with Fluosol DA cardioplegic solution did not
      take up as much oxygen as hearts receiving blood cardioplegic reperfusion (37
      versus 54 ml/100 gm, p less than 0.05). Blood cardioplegia was superior to
      Fluosol DA cardioplegia in recovery of segmental contractility (69% versus 34%
      systolic shortening, p less than 0.05), produced less edema (79.5% versus 80.9%
      water content, p less than 0.05), and produced less histochemical damage with
      triphenyltetrazolium chloride (11% versus 40% area of nonstaining/area at risk, p
      less than 0.05). CONCLUSIONS: Initial reperfusion with a blood cardioplegic
      solution ensures better oxygen utilization, superior recovery of regional
      contractility, and less tissue damage than Fluosol DA cardioplegic reperfusion.
      These data emphasize the importance of including blood components (plasma or red
      blood cells) in the oxygenated cardioplegic reperfusate to limit reperfusion
      injury.

PMID- 1992240
TI  - Studies of controlled reperfusion after ischemia. XX. Reperfusate composition:
      detrimental effects of initial asanguineous cardioplegic washout after acute
      coronary occlusion.
AB  - This study tests whether initial asanguineous washout of potentially toxic
      substances that accumulate during ischemia improves recovery produced by blood
      cardioplegic reperfusion and evaluates the role of plasma versus whole blood
      cardioplegia. METHODS: Twenty-four dogs underwent 2 hours of occlusion of the
      left anterior descending coronary artery and 20 minutes of blood cardioplegic
      reperfusion on total vented bypass. In 13 dogs, a 5-minute infusion of either a
      crystalloid (n = 7) or plasma (n = 6) cardioplegic solution (containing the same
      pH, calcium potassium, and osmolarity as blood cardioplegia) was given
      immediately before reoxygenation with blood cardioplegia. Regional oxygen uptake
      and coronary vascular resistance were measured during controlled reperfusion, and
      segmental shortening (ultrasonic crystals), tissue water content, and
      histochemical damage (triphenyltetrazolium chloride stain) were assessed 1 hour
      after bypass was discontinued. RESULTS: Asanguineous cardioplegic washout before
      reoxygenation with blood cardioplegic solution resulted in a progressive (+42%)
      increase in coronary vascular resistances (from 123 to 176 units, p less than
      0.05) and low oxygen utilization during 20 minutes of blood cardioplegic
      reperfusion (29 ml/100 gm, p less than 0.05); coronary vascular resistance
      remained low throughout blood cardioplegic reperfusion without washout (from 109
      to 98 units), and oxygen utilization was 54 ml/100 gm (p less than 0.05). Neither
      plasma nor crystalloid washout restored substantial regional systolic shortening
      (3% systolic shortening versus 73% systolic shortening with blood cardioplegia),
      and asanguineous washout caused more myocardial edema (81.1% +/- 80.9% versus
      79.5% water content, p less than 0.05) and produced extensive transmural
      triphenyltetrazolium chloride damage (48% +/- 41% versus 8% nonstaining in area
      at risk, p less than 0.05) than initial blood cardioplegic reperfusion.
      CONCLUSION: Asanguineous cardioplegic washout before blood cardioplegic
      reperfusion limits oxygen utilization during subsequent controlled reperfusion,
      restricts early recovery of systolic shortening, allows more myocardial edema,
      and produces extensive histochemical damage, which may be avoided by initial
      reoxygenation with blood cardioplegia. The red blood cells appear more important
      than the plasma components of blood cardioplegia.

PMID- 1992242
TI  - Lowering the calcium concentration in St. Thomas' Hospital cardioplegic solution
      improves protection during hypothermic ischemia.
AB  - The concentration of calcium (1.2 mmol/L) in clinical St. Thomas' Hospital
      cardioplegic solution was chosen several years ago after dose-response studies in
      the normothermic isolated heart. However, recent studies with creatine phosphate
      in St. Thomas' Hospital solution demonstrated that additional myocardial
      protection during hypothermia resulted principally from its calcium-lowering
      effect in the solution. The isolated working rat heart model was therefore used
      to establish the optimal calcium concentration in St. Thomas' Hospital solution
      during lengthy hypothermic ischemia (20 degrees C, 300 minutes). The calcium
      content of standard St. Thomas' Hospital solution was varied from 0.0 to 1.5
      mmol/L in eight treatment groups (n = 6 for each group). During ischemia, hearts
      were exposed to multidose cardioplegia (3 minutes every 30 minutes). Postischemic
      recovery of function was expressed as a percentage of preischemic control values.
      Release of creatine kinase and the time to return of sinus rhythm during the
      reperfusion period were also measured. These dose-response studies during
      hypothermic ischemia revealed a broad range of acceptable calcium concentrations
      (0.3 to 0.9 mmol/L), which appear optimal in St. Thomas' Hospital solution at 0.6
      mmol/L. This concentration improved the postischemic recovery of aortic flow from
      22.0% +/- 5.9% with control St. Thomas' Hospital solution (calcium concentration
      1.2 mmol/L) to 86.0% +/- 4.0% (p less than 0.001). Other indices of functional
      recovery showed similar dramatic results. Creatine kinase release was reduced 84%
      (p less than 0.01) in the optimal calcium group. Postischemic reperfusion
      arrhythmias were diminished with the loser calcium concentration, with a
      significant decrease in the time between initial reperfusion until the return of
      sinus rhythm. In contrast, acalcemic St. Thomas' Hospital solution precipitated
      the calcium paradox with massive enzyme release and no functional recovery.
      Unlike prior published calcium dose-response studies at normothermia, these
      results demonstrate that the optimal calcium concentration during clinically
      relevant hypothermic ischemia is considerably lower than that of normal serum
      ionized calcium (1.2 mmol/L) and appears ideal at 0.6 mmol/L to realize even
      greater cardioprotective and antiarrhythmic effects with St. Thomas' Hospital
      solution.

PMID- 1992241
TI  - Studies of controlled reperfusion after ischemia. XXI. Reperfusate composition:
      superiority of blood cardioplegia over crystalloid cardioplegia in limiting
      reperfusion damage--importance of endogenous oxygen free radical scavengers in
      red blood cells.
AB  - Postischemic damage is caused partially by oxygen free radical-mediated injury.
      This study will show that (1) crystalloid cardioplegia with room air oxygen is
      deleterious because it is devoid of free radical scavengers and (2) blood
      cardioplegia limits damage because it contains endogenous free radical scavengers
      in red blood cells. METHODS: Thirty-two dogs underwent 2 hours of ligation of the
      left anterior descending coronary artery followed by 20 minutes of regional blood
      cardioplegic reperfusion on bypass. Ten dogs received only the blood cardioplegic
      solution (containing its endogenous free radical scavengers); five received
      initial blood cardioplegia (5 minutes) with endogenous free radical scavengers
      (catalase and glutathione peroxidase) blocked by aminotriazole and N
      ethylmaleimide, respectively; 12 received initial crystalloid cardioplegic
      solution oxygenated by room air (oxygen tension = 150 mm Hg); seven without and
      five with exogenous free radical scavengers (superoxide dismutase, catalase,
      coenzyme Q10); five received initial deoxygenated crystalloid cardioplegic
      solution (oxygen tension = 6 mm Hg); and five received deoxygenated crystalloid
      cardioplegic solution. RESULTS: Blood cardioplegia with endogenous free radical
      scavengers produced the best recovery of systolic shortening (69% systolic
      shortening) and resulted in the least histochemical damage (11%
      triphenyltetrazolium chloride nonstaining). The worst recovery and most damage
      occurred if blood cardioplegia was preceded by oxygenated crystalloid
      cardioplegia (3% systolic shortening, 48% triphenyltetrazolium chloride
      nonstaining; p less than 0.05 versus blood cardioplegia) or if free radical
      scavengers were blocked in the initial period of blood cardioplegia (3% systolic
      shortening, 41% triphenyltetrazolium chloride nonstaining; p less than 0.05
      versus blood cardioplegia). Conversely, deoxygenation or supplementation of
      oxygenated crystalloid cardioplegic solution with exogenous free radical
      scavengers restored 60% systolic shortening (p less than 0.05 versus oxygenated
      crystalloid cardioplegia) and 54% systolic shortening (p less than 0.05 versus
      oxygenated crystalloid cardioplegia) and reduced damage to 34% and 21% (both p
      less than 0.05 versus oxygenated crystalloid cardioplegia). CONCLUSION: Blood
      cardioplegic solutions containing their own endogenous free radical scavengers
      are superior to crystalloid cardioplegic solutions, because they limit oxygen
      mediated perfusion damage and restore contractile function. Initial crystalloid
      cardioplegic washout negates the salutary effect of blood cardioplegia. Exogenous
      free radical scavenger supplementation or deoxygenation of the cardioplegic
      reperfusate is necessary only if crystalloid cardioplegia is used.

PMID- 1992243
TI  - Recovery of the neonatal heart after normothermic ischemia. Effect of oxygen and
      catalase.
AB  - The objective of this study was to determine the effect of oxygen and the oxygen
      radical-scavenging enzyme catalase on the neonatal rabbit heart exposed to global
      ischemia. The experiments were performed with an isolated neonatal (7 to 10 days
      of age) working heart model in which normothermic (37 degrees C) ischemia was
      produced for 60 minutes. Left ventricular developed pressure, ratio of change of
      ventricular pressure to change in time, and aortic flow were measured before
      ischemia and 30 minutes after reperfusing the hearts with physiologic saline
      solution. In the control group (ischemia only), developed pressure and ratio of
      change of ventricular pressure to change in time recovered to 27% +/- 3% (mean +/
      standard error of the mean) and 24% +/- 7% of baseline; the hearts were
      incapable of ejecting (aortic flow = 0). Treatment of hearts before and after
      ischemia with catalase (150 units/ml of perfusate) was studied in a second group
      (control plus catalase), but functional recovery (developed pressure = 32% +/-
      1%; ratio of change of ventricular pressure to change in time = 24% +/- 2%, and
      aortic flow = 0) was not significantly different from the control group. The
      effect of washout midway through the ischemic period with a low oxygen (oxygen
      concentration less than 35 mm Hg) solution was measured in a third group (hypoxic
      physiologic saline solution). Functional recovery (developed pressure = 13% +/-
      3%; ratio of change of ventricular su pressure to change in time = 13% + 2%;
      aortic flow = 0) was not significantly different from the control and control
      plus catalase groups. In marked contrast were the effects of washout with an
      oxygenated (oxygen concentration greater than 500 mm Hg) solution (oxygenated
      physiologic saline solution) in which functional recovery (developed pressure =
      78% +/- 3%; ratio of change of ventricular pressure to change in time = 80% +/-
      3%; aortic flow = 39% +/- 9%) was significantly better than in the control,
      control plus catalase, and hypoxic physiologic saline solution groups. Use of
      modified St. Thomas' Hospital cardioplegic solution (cardioplegic solution group)
      during the ischemic period also resulted in substantial functional recovery
      (developed pressure = 80% +/- 3%; ratio of change of ventricular pressure to
      change in time = 78% +/- 5%; aortic flow = 64% +/- 7%) that did not differ
      significantly from that in the oxygenated physiologic saline solution
      group.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1992244
TI  - Deleterious effects of digitalis on newborn rabbit myocardium after simulated
      cardiac surgery.
AB  - We studied the effect of the digitalis glycoside ouabain on isolated blood
      perfused neonatal (4- to 6-day-old) rabbit hearts during 60 minutes of
      hypothermic/ischemic arrest (at 15 degrees C), simulating conditions during
      cardiac surgery. Compared with a control (no ouabain) group, both low- and high
      dose ouabain groups had increased left ventricular diastolic chamber stiffness
      ("contracture") during and after the arrest period. The high-dose ouabain group
      also showed less recovery of contractile function than did the control group. We
      conclude that digitalis glycosides have the potential to impair recovery of
      myocardial function in the newborn infant after hypothermic/ischemic arrest;
      myocardial relaxation and diastolic function appear more sensitive to this
      manifestation of digitalis toxicity than does contractile function.

PMID- 1992245
TI  - Effects of potassium cardioplegia on high-energy phosphate kinetics during
      circulatory arrest with deep hypothermia in the newborn piglet heart.
AB  - The protective effects of hypothermia and potassium-solution cardioplegia on high
      energy phosphate levels and intracellular pH were evaluated in the newborn piglet
      heart by means of in vivo phosphorus nuclear magnetic resonance spectroscopy. All
      animals underwent cardiopulmonary bypass, cooling to 20 degrees C, 120 minutes of
      circulatory arrest, rewarming with cardiopulmonary bypass, and 1 hour off
      extracorporeal support with continuous hemodynamic and nuclear magnetic resonance
      spectroscopic evaluation. Group I (n = 5) was cooled to 20 degrees C; group II (n
      = 4) was given a single dose of 20 degrees C cardioplegic solution; group III (n
      = 7) was given a single dose of 4 degrees C cardioplegic solution; and group IV
      (n = 4) received 4 degrees C cardioplegic solution every 30 minutes. At end
      ischemia, adenosine triphosphate, expressed as a percent of control value, was
      lowest in group I 54% +/- 6.5% but only slightly greater in group II 66% +/-
      7.0%. Use of 4 degrees C cardioplegic solution in groups III and IV resulted in a
      significant decrease in myocardial temperature, 9.9 degrees C versus 17 degrees
      to 20 degrees C, and significantly higher levels of adenosine triphosphate at end
      ischemia; with group III levels at 72% +/- 6.0% and group IV levels at 73% +/-
      6.0%. Recovery of adenosine triphosphate with reperfusion was not related to the
      level of adenosine triphosphate at end ischemia and was best in groups I and II,
      with a recovery level of 95% +/- 4.0%. In group IV, no recovery of adenosine
      triphosphate occurred with reperfusion, resulting in a significantly lower level
      of adenosine triphosphate, 74% +/- 6.0%, than in groups I and II. Recovery of
      ventricular function was good for all groups but was best in hearts receiving a
      single dose of 4 degrees C cardioplegic solution. In this model, multiple doses
      of cardioplegic solution were not associated with either improved adenosine
      triphosphate retention during arrest or improved ventricular function after
      reperfusion, and in fact resulted in a significantly lower level of adenosine
      triphosphate with reperfusion. The complete recovery of adenosine triphosphate in
      groups I and II, despite a nearly 50% adenosine triphosphate loss during
      ischemia, may result from a decrease in the catabolism of the metabolites of
      adenosine triphosphate consumption in the newborn heart.

PMID- 1992246
TI  - Studies of controlled reperfusion after ischemia. XXII. Reperfusate composition:
      effects of leukocyte depletion of blood and blood cardioplegic reperfusates after
      acute coronary occlusion.
AB  - OBJECTIVES: This study evaluates the role of leukocyte depletion during initial
      reoxygenation with normal blood and blood cardioplegic reperfusates in limiting
      reperfusion damage. METHODS: Twenty-eight dogs underwent 2 hours of ligation of
      the left anterior descending coronary artery. The initial reperfusate (37 degrees
      C) was delivered on total vented bypass to the left anterior descending artery by
      a calibrated pump via an internal mammary artery graft at 50 mm Hg for 20
      minutes. Eight dogs received normal (normokalemic, nonenriched) blood reperfusion
      (leukocyte count 8000/mm3) and six were reperfused with leukocyte-depleted normal
      blood (leukocyte count less than 100/mm3). Of 14 dogs reperfused with substrate
      enriched (hyperkalemic) blood cardioplegic solution, six received a cardioplegic
      solution with a leukocyte count less than 100/mm3. RESULTS: Leukocyte depletion
      of normal blood reduced reperfusion-induced arrhythmias from 63% to 17% (p less
      than 0.05). Coronary vascular resistance at initial reperfusion was low and
      remained low during substrate-enriched blood cardioplegic reperfusion with both
      normal and reduced leukocyte counts. In contrast, coronary vascular resistance
      rose 63% with normal blood reperfusion, and this increase was avoided by
      leukocyte depletion (2.6 versus 4.0 mm Hg x ml/min, p less than 0.05). Coronary
      vascular resistance after 20 minutes was, however, higher than that with blood
      cardioplegia with normal or decreased leukocyte counts. Negligible functional
      recovery followed reperfusion with normal blood and leukocyte-depleted blood (12%
      and 6% of control systolic shortening). In contrast, substantial segmental
      recovery followed blood cardioplegic reperfusion (73% systolic shortening, p less
      than 0.05) but was not improved by leukopheresis (81% systolic shortening).
      Leukocyte depletion of normal blood reperfusate reduced histochemical damage from
      53% to 38% (p less than 0.05), but the least histochemical damage followed blood
      cardioplegic reperfusion with a normal or reduced leukocyte count (8% or 11%, p
      less than 0.05). CONCLUSIONS: These findings suggest an important role for
      leukocytes in reperfusion damage, but reperfusate leukocyte filtration alone is
      inferior to blood cardioplegic reperfusion. Leukocyte depletion of blood
      cardioplegic solutions seems unnecessary after only 2 hours of ischemia.

PMID- 1992247
TI  - Twenty years' results with internal thoracic artery-coronary artery anastomosis.

PMID- 1992248
TI  - Cell-mediated immunity after cardiac operations.

PMID- 1992249
TI  - No flow during low-flow cardiopulmonary bypass.

PMID- 1992250
TI  - Invited letter concerning: No flow during cardiopulmonary bypass.

PMID- 1992251
TI  - Invited letter concerning: Long-term follow-up comparing subclavian flap
      angioplasty to resection with modified oblique end-to-end anastomosis.

PMID- 1992252
TI  - The history of the surgery of mitral valves.

PMID- 1992253
TI  - Muscle flap closure of a complicated upper esophageal disruption.

PMID- 1992254
TI  - Commissural fusion in an Ionescu-Shiley bioprosthesis: an unusual cause of
      valvular stenosis.

PMID- 1992255
TI  - Synthetic erythropoietin and Jehovah's Witnesses.

PMID- 1992256
TI  - Surgical treatment of an isolated coronary artery aneurysm: an alternative
      approach.

PMID- 1992257
TI  - Coronary angiography during cardiac arrest: a missed opportunity?

PMID- 1992258
TI  - Neurofibromatosis type 2: report of a family and review of current evaluation and
      treatment.
AB  - Significant advances during the past decade have greatly improved our
      understanding of neurofibromatosis type 2, a genetic disease which results in
      bilateral acoustic neuromas. The emergence of gadolinium-enhanced magnetic
      resonance imaging has allowed early detection of minute intracanalicular eighth
      nerve tumors, less than 1 cm in diameter. Recombinant DNA studies have clarified
      the genetics that underlie neurofibromatosis type 2 and separate it from a
      variety of related conditions, such as von Recklinghausen's neurofibromatosis.
      Early diagnosis and surgical removal of these tumors may offer the only hope of
      preserving hearing and facial nerve function. A report of the evaluation and
      treatment of a family with multiple affected individuals will exemplify these
      conclusions.

PMID- 1992259
TI  - Infiltration of epinephrine in tonsillectomy: a randomized, prospective, double
      blind study.
AB  - A variety of hemostatic agents and techniques have been used in an attempt to
      reduce intraoperative blood loss and postoperative bleeding in tonsillectomy. The
      efficacy of most of these substances and techniques has been judged primarily on
      clinical impressions. Because of the paucity of prospective studies, a
      randomized, prospective, double-blind study, using the patients as their own
      controls, was conducted. Ninety-two patients were injected before tonsillectomy
      in a random, double-blind fashion with normal saline solution in one tonsil and
      1:100,000 epinephrine in the other. The blood loss, time of dissection, and
      postoperative bleeding were recorded separately for each tonsil. Cardiac
      manifestations were also monitored. The tonsils injected with epinephrine had a
      statistically significant reduction in blood loss and dissection time when
      compared with those injected with normal saline. Subjectively, dissection was
      easier on the epinephrine-injected side. There was no difference in the incidence
      of postoperative hemorrhage. Cardiac manifestations of epinephrine were minimal
      and transient. This study demonstrates that epinephrine is useful in reducing
      hemorrhage during tonsillectomy and can be used safely with the appropriate
      inhalation anesthetics.

PMID- 1992260
TI  - Imaging modalities in recurrent head and neck tumors.
AB  - Patients with recurrent neoplasms of the head and neck present perplexing
      management problems, and accurate preoperative assessment of their disease is
      crucial. Thirty-eight patients with suspected recurrent neoplasms comprise this
      study: 30 had computed tomography scans, 4 had magnetic resonance images, and 4
      patients underwent both computed tomography and magnetic resonance imaging to
      assess the anatomical extent of pathology in 34 malignant and 4 benign tumors.
      Contrast enhancement was essential for detecting disease on computed tomography
      scan. Differentiation of recurrent tumor was more difficult when the patient had
      undergone radiation. Magnetic resonance imaging demonstrated superior visibility
      in recurrent parotid and paranasal sinus neoplasm, but was less helpful in
      laryngeal and pharyngeal recurrences. Computed tomography demonstration of a mass
      with infiltration of normal fat or tissue planes or lymphadenopathy correlated
      highly with recurrent disease. Imaging techniques and fine points for determining
      recurrent neoplasms are presented.

PMID- 1992261
TI  - Management decisions in laryngeal carcinoma in situ.
AB  - Twenty-one patients with laryngeal carcinoma in situ (n = 12) or carcinoma in
      situ with microinvasion (n = 9) were treated with laser mucosal dissection of the
      vocal cords and/or superficial laser cordectomy. The normal architecture of the
      vocal cords was preserved because the depth of vaporization was usually
      superficial in these early cases. Five patients had recurrence, new tumor, or
      persistence of abnormal tissue that required additional laser surgical
      treatments. With a follow-up range of 6 months to 4 years, all patients currently
      are free of laryngeal abnormality, and no patient has needed open laryngeal
      surgery or radiation therapy. Transoral endoscopic laser resection of laryngeal
      carcinoma in situ with or without microinvasion should be the treatment of choice
      for these early lesions.

PMID- 1992262
TI  - Extracranial repair of cerebrospinal fluid otorhinorrhea.
AB  - Forty-eight patients with cerebrospinal fluid leaks comprise this retrospective
      study. There were 39 traumatic and 9 spontaneous leaks. Nine patients were
      initially managed with bed rest and spinal drainage, but 3 patients in this group
      ultimately required surgical intervention for repair of their persistent leaks.
      Thirty-nine patients had surgery as initial therapy, with 33 extracranial
      repairs, 2 intracranial repairs, and 4 combined approaches. The extracranial
      approach was used in 36 of 42 patients, with an initial success rate of 86%.

PMID- 1992263
TI  - The hypotympanum and infralabyrinthine cells in chronic otitis media.
AB  - Despite the localization implied by the term "chronic otitis media," little
      attention has been paid to the role of the hypotympanum in chronic active otitis
      media. Most authors have emphasized the role of recurrent cholesteatoma or
      unexenterated cells in the mastoid cell system as causes of recurrent disease.
      Seven cases are reported in which clinical evidence indicated that recurrent
      chronic otitis media was limited to the hypotympanum and infralabyrinthine cell
      system. In the five cases in which revision surgery was done, exenteration of
      this area resulted in an asymptomatic ear. The anatomy, radiographic evaluation,
      and surgical approach to the hypotympanum are reviewed. Careful inspection of the
      hypotympanum in primary surgery for chronic ear disease and exenteration of the
      hypotympanic and proximal infralabyrinthine cell tract are advocated when these
      regions contain cholesteatoma or extensive granulomatous disease.

PMID- 1992264
TI  - Holmium: yttrium aluminum garnet laser-assisted endoscopic sinus surgery:
      laboratory experience.
AB  - Endoscopic sinus surgery has gained wide acceptance since its introduction into
      the United States. Complex sinus anatomy and troublesome bleeding have been
      associated with complications, which vary in severity from synechia to blindness
      and leakage of cerebrospinal fluid. Endoscopic sinus surgery using a holmium:
      yttrium aluminum garnet pulsed solid-state laser oscillating at 2.1 microns with
      fiberoptic delivery was performed in the laboratory, and the results were
      compared with those of conventional endoscopic sinus surgery. Three beagle dogs,
      six human cadaver heads, and one calf head were used in the in vivo and in vitro
      studies to evaluate the bone ablation, tissue coagulation, and hemostatic
      properties of the holmium: yttrium aluminum garnet laser. Modified endoscopic
      telescopes for sinus surgery, a newly developed handpiece for fiberoptic
      delivery, and other surgical instruments were used. The results indicate that the
      holmium: yttrium aluminum garnet laser and new delivery instrumentation provide
      good hemostasis and controlled soft-tissue ablation and bone removal. The access
      to all sinuses in the human cadaver model was very good. The canine in vivo study
      showed delayed but complete healing on the laser-treated side. Clinical
      evaluation of the holmium: yttrium aluminum garnet laser is warranted to increase
      the precision and safety of endoscopic sinus surgery.

PMID- 1992265
TI  - Electromyography of masticatory muscles in craniomandibular disorders.
AB  - Patients presenting to the otolaryngologist with complaints such as otalgia,
      dizziness, tinnitus, or fullness in the ear may be experiencing the effects of
      craniomandibular disorders. These disorders can involve dysfunction in the
      delicate interrelationship of the skull, mandible, cervical vertebrae, and
      neuromuscular apparatus and can present as myofacial pain. Electromyographic
      recordings using surface electrodes were made bilaterally on the masseter,
      anterior temporalis, and digastric muscles in 641 craniomandibular patients,
      before and after transcutaneous electrical neural stimulation, at their initial
      presentation and following the insertion of mandibular orthopedic appliances. In
      the presenting patient, muscle-resting levels significantly decreased from
      hyperactive levels with transcutaneous electrical neural stimulation therapy. The
      creation of a new occlusal position with an orthotic appliance was found to
      correlate with a significant reduction in otolaryngologic symptoms as well as an
      increase in maximum muscle activity in function and coordination of muscle groups
      during mandibular movement. Thus, clinical electromyographic studies are an
      important aid in the treatment of craniomandibular disorders.

PMID- 1992266
TI  - Photodynamic therapy using rhodamine-123 as a new laser dye: biodistribution,
      metabolism and histology in New Zealand rabbits.
AB  - Rhodamine-123 (Rh-123) has been tested recently as a new laser dye for
      photodynamic therapy of human tumors in vitro and in vivo. Prior to initiation of
      clinical studies of this technique, we evaluated the biodistribution, metabolism,
      and pathological changes of Rh-123 in rabbits after systemic, repetitive
      injections of the dye in escalating doses. At doses between 0.1 to 1 mg/kg of Rh
      123 injected intramuscularly (IM) daily for 5 days, no local or systemic toxicity
      was observed during the 4 weeks of follow-up. The peak concentrations of Rh-123
      in micrograms/g of tissue was distributed as follows: kidney (3.24) greater than
      heart (2.24) greater than spleen (1.77) greater than lung (0.61) greater than
      liver (0.38) greater than skin (0.30) greater than skeletal muscle (0.17) greater
      than genitals (0.13) greater than brain (0.04). The elimination of Rh-123 was
      very rapid, with the dye falling to 2.7% of peak concentration at 72 hours in the
      kidneys, and to undetectable levels at 240 hours postinjection in all organs,
      except the skin, which retained 3% of the peak level at 240 hours. The low
      toxicity and rapid metabolism of Rh-123 in this preclinical model suggests that
      the dye and Argon laser may represent an effective combination for treatment of
      superficial malignancies.

PMID- 1992267
TI  - Characterization of cytokines present in middle ear effusions.
AB  - Retention of inflammatory mediators and cells in the middle ear cleft during
      chronic otitis media with effusion (COME), results in ongoing inflammation with
      the potential for pathologic changes and hearing loss. Cytokines are
      glycoproteins produced by macrophages and other cells. Activities of cytokines
      include fever production, osteoclast, fibroblast, phagocyte and cytotoxic cell
      activation, regulation of antibody formation, and inhibition of cartilage, bone
      and endothelial cell growth. Using enzyme-linked immunospecific assays we
      measured levels of six cytokines in middle ear effusions (MEE) from children with
      COME. Significant levels of four cytokines: interleukin-1-beta (greater than 50
      pg/ml), interleukin-2 (greater than 300 pg/ml), tumor necrosis factor-alpha
      (greater than 40 pg/ml), and gamma-interferon (greater than 6.25 pg/ml) were
      found in 51%, 54%, 63%, and 19% of MEE, respectively. In contrast, levels of a
      fifth cytokine, granulocyte-macrophage colony-stimulating factor, and a sixth
      cytokine, interleukin-4, were undetectable. Age was observed to have a
      significant effect on the levels of specific cytokines. Interleukin-1 (IL-1)
      correlated inversely (P less than .02) with age such that the younger the child,
      the higher the level of IL-1 in MEE. Tumor necrosis factor-alpha (TNF) correlated
      directly (P less than .005) with age such that the older the child, the higher
      the level of TNF in MEE. Children undergoing tympanostomy on multiple occasions
      had average MEE TNF levels (234.2 +/- 109.1 pg/mg total protein) that were nearly
      14 times higher (P less than .005) than those from children undergoing their
      first tympanostomy (16.9 +/- 3.0 pg/mg total protein). Thus IL-1 correlated with
      the early stages of COME, while TNF correlated with persistence of disease. The
      presence of these cytokines in MEE may be responsible for the mucosal damage,
      bone erosion, fibrosis, and resulting hearing loss seen in some cases of COME.

PMID- 1992268
TI  - Aerobic and anaerobic microbiology of acute suppurative parotitis.
AB  - Aspirates of pus from acute suppurative parotitis were studied for aerobic and
      anaerobic bacteria. Bacterial growth was present in 23 specimens. A total of 36
      bacterial isolates (20 anaerobic and 16 aerobic and facultative) were recovered,
      accounting for 1.6 isolates per specimen (0.9 anaerobic and 0.7 aerobic and
      facultative). Anaerobic bacteria only were present in 10 (43%) patients, aerobic
      and facultatives in 10 (43%), and mixed aerobic and anaerobic flora in 3 (13%).
      Single bacterial isolates were recovered in 9 infections, 6 of which were
      Staphylococcus aureus and 3 were anaerobic bacteria. The predominant bacterial
      isolates were S. aureus (8 isolates), Bacteroides sp. (6 isolates, including 4
      Bacteroides melaninogenicus group), and Peptostreptococcus sp. (5). beta
      Lactamase-producing organisms were recovered from 11 (73%) of the 15 specimens
      tested. This study highlights the polymicrobial nature and importance of
      anaerobic bacteria in acute suppurative parotitis.

PMID- 1992269
TI  - Diving-related inner ear injuries.
AB  - Diving-related inner ear barotrauma (IEB) and inner ear decompression sickness
      (IEDS) most often result in permanent severe cochleovestibular deficits, unless
      immediate diagnosis is reached and the correct treatment is commenced early. Nine
      cases of sport-diving-induced inner ear injuries that were referred to the
      Israeli Naval Hyperbaric Institute between October 1987 and September 1989 are
      presented with regard to evaluation, treatment, and follow-up. The diagnosis was
      IEB in five divers and IEDS in four. Explorative tympanotomy was carried out with
      remarkable results in two patients with IEB, while the remaining three were
      relieved by bed rest alone. Three of the four IEDS patients were recompressed
      according to the extended US Navy Table 6 with good short-term results. The role
      of complete otoneurological evaluation in the decision-making process leading to
      the correct diagnosis and treatment is emphasized.

PMID- 1992270
TI  - The Glasgow Benefit Plot: a new method for reporting benefits from middle ear
      surgery.
AB  - Conventionally, the results of middle ear surgery are reported in terms of
      postoperative closure of the air-bone gap or the improvement in air-conduction
      thresholds. While these are relevant in that they assess the technical success of
      the procedure and the lessening of monaural disability, they do not necessarily
      assess whether the patient has benefited. This is determined by many factors, not
      least of which is the hearing in the nonoperated ear. In this paper, we suggest
      that preoperative and postoperative plots of the air-conduction thresholds in
      both ears be used as an additional method of presenting the results. First, the
      proportion of patients that fall into each of three main preoperative impairment
      groups are identified. This is important, as the potential benefits from surgery
      are not the same in each group. Thereafter, the percentages of patients that
      achieve various postoperative hearing categories can be calculated, allowing
      surgeons to audit their results and make comparisons between series.

PMID- 1992271
TI  - Use of the excimer laser in stapes surgery and ossiculoplasty of middle ear
      ossicles: preliminary report of an experimental approach.
AB  - Surgery of the stapes may cause a number of complications, including hearing
      deficits and balance disorders. This has made it necessary to look for improved
      techniques. Small-fenestra stapedotomy has recently been popularized. Lasers have
      been advocated for use in fenestrating the stapes footplate. On the other hand,
      sculpting the middle ear ossicles during tympanoplasty is often necessary for the
      reconstruction of the ossicular chain and the improvement of sound conduction.
      Using an excimer laser with a wavelength of 193 nm, fenestrations of the
      footplate and ossicular sculpting were performed on ossicles obtained during ear
      surgery and from human cadaver temporal bones. The results indicate that the
      excimer laser can be used effectively and accurately on an experimental basis and
      that further research is needed before this method can be used for clinical
      purposes.

PMID- 1992272
TI  - Sinusoidal harmonic acceleration testing in normal humans.
AB  - Forty-one normal humans were tested with sinusoidal harmonic acceleration. Phase
      lag at 0.01, 0.02, and 0.04 Hz was the most stable parameter, with less test
      retest variability than gain and asymmetry. There was no significant difference
      between men and women for phase lag, gain, or asymmetry at any of the five
      testing frequencies. Gain decreased as age increased. Age had no effect on phase
      lag at most test frequencies or on asymmetry at any frequency.

PMID- 1992273
TI  - The changing direction of nystagmus in acute Meniere's disease:
      pathophysiological implications.
AB  - The direction(s) and pathophysiologic basis of nystagmus during an acute attack
      of Meniere's disease have been subject to much debate in the world literature.
      Clinical recordings from two patients whose nystagmus was captured near the very
      beginning of the acute vertiginous episode are presented. Previous clinical
      observations in Meniere's disease, experimental animal models concerned with
      initiation of peripheral nystagmus, and the phenomenon of recovery are discussed.

PMID- 1992274
TI  - Three-dimensional computerized tomography in the evaluation of laryngeal injury.
AB  - A comparison of diagnostic information obtained from the physical examination,
      conventional two-dimensional axial computerized tomography scanning (2-D CT), and
      three-dimensional display computerized tomography (3-D CT) was performed in five
      patients sustaining laryngeal trauma. Four patients had laryngeal fractures and
      one patient had an incompletely ossified thyroid cartilage (normal variant)
      simulating a fracture by 2-D CT. Three-dimensional display computerized
      tomography was found superior to conventional 2-D CT in assessing the presence
      and nature of the laryngeal injuries while correctly identifying the anatomic
      variant.

PMID- 1992275
TI  - One-piece reimplantation treatment of the "Humpty Dumpty" frontal bone fracture.

PMID- 1992276
TI  - The treatment of Meniere's disease: Torok revisited.

PMID- 1992277
TI  - Portex "Talk" Tube.

PMID- 1992278
TI  - Congenital absence of the oval window.

PMID- 1992279
TI  - Occurrence of "natural" benzodiazepines.
AB  - There is accumulating evidence that benzodiazepines (BZD)--agents widely used as
      anxiolytics and hypnotics-could be regarded as "natural" drugs since they have
      been found in trace amounts also in plants, various tissues of different animal
      species and even humans. The biosynthesis of such BZD is still unknown and the
      hypothesis is favoured that they may be of plant origin. Besides diazepam (D) and
      its major metabolite desmethyldiazepam (DD) several other BZD (e.g. delorazepam,
      deschloro-diazepam, delormetazepam, isodiazepam, lormetazepam, oxazepam) could be
      detected. In some cases identification of these compounds was accomplished by
      specific mass spectrometry (GC-MS) and for quantification various methods have
      been applied resulting in different concentrations which range for D from about
      0.005 to 1 ng/g and for DD from 0.01 to 0.5 ng/g. It is very unlikely that these
      trace amounts exert any direct pharmacological effects and at the moment only
      speculations upon their physiological/biological role are possible. Recently BZD
      receptor binding activity equivalent to surprisingly high levels of more than 900
      ng/ml was found in cerebrospinal fluid of patients with advanced hepatic
      encephalopathy. As long as the structure of this binding activity has not been
      elucidated no firm conclusions can be drawn from these findings. If pertinent
      analytical problems (e.g. drug-free biological material; exact quantification by
      internal standard techniques) are solved and if the source(s) of BZD are
      established it might be possible to answer also the critical question whether
      "endogenous" or "natural" BZD play any (in-) direct role in the regulation of CNS
      activity.

PMID- 1992280
TI  - Effects of DL-alpha-difluoromethylornithine, 4-deoxypyridoxine and methylglyoxal
      bis(guanylhydrazone) on allograft prolongation.
AB  - DL-alpha-difluoromethylornithine (DFMO), 4-deoxypyridoxine (4-DOP), and
      methylglyoxal bis (guanylhydrazone) (MGBG) were tested as inhibitors of acute
      skin graft rejection. Proximal full thickness tail skins were exchanged between
      C57BL/6 and Balb/C mice. Distal autografts were placed to monitor healing.
      Inhibitors were given singly or in combination, either orally or by injection, in
      various schedules to 10 groups of mice. Compared to controls, singly treated mice
      had significant mean prolongation of allografts ranging from 126% to 141%.
      Likewise, DFMO plus MGBG extended mean time of complete rejection ranging from
      172% to 206%. Autografts remained intact. Some grafts persisted after
      discontinued immunosuppression. Complete rejection was preceded by a decline in
      vascularity of the graft bed and/or gradual replacement by host tissue. Graft
      protection in such stringent circumstances i.e., the use of skin in strains with
      complete histoincompatibility at the H-2 MHC loci, clearly indicate the anti
      rejection effects of polyamine synthesis inhibitors. Moreover, primary and
      secondary effects of DFMO establish the critical role of polyamine pathway
      activation in acute rejection. In doses and schedules used, toxicity was
      encountered when DFMO and 4-DOP were used in combination and when increased
      amounts of MGBG were administered.

PMID- 1992281
TI  - Prolactin-stimulated ornithine decarboxylase induction in rat hepatocytes:
      coupling to diacylglycerol generation and protein kinase C.
AB  - The trophic effects of prolactin (PRL) in rat liver have been linked to
      activation of protein kinase C (PKC). Since alterations in PKC activity imply its
      activation by 1,2-diacylglycerol (DAG), we tested whether PRL treatment
      stimulated DAG generation coupled to induction of a growth response in primary
      hepatocytes. Addition of PRL to hepatocyte cultures significantly increased [3H]
      glycerol incorporation into DAG within 5 minutes which was followed by a loss of
      cytosolic PKC activity by 10 minutes. Prolactin also significantly enhanced
      radiolabel incorporation into triacylglycerol and phospholipids within 10 minutes
      and induced ODC activity at 6 hours. Therefore, prolactin-stimulated alterations
      in PKC activity are preceded by enhanced DAG generation. Moreover, these events
      appear to be coupled to PRL-stimulated entry of hepatocytes into cell cycle.

PMID- 1992282
TI  - Lung contains an inhibitor for nicotinatemononucleotide pyrophosphorylase
      (carboxylating) of NAD biosynthesis.
AB  - Rat, cow and foal lung extracts contained an inhibitor for the liver NAD
      biosynthetic-pathway enzyme, nicotinatemononucleotide pyrophosphorylase
      (carboxylating) [EC 2.4.2.19]. The inhibitor was not dialyzable, was labile at
      100 degrees C, was retained by a 30,000 dalton pore size Amicon membrane and,
      when partially purified by precipitation at 40-100% ammonium sulfate, inhibited
      the enzyme stoichiometrically. Lung reportedly does not contain nicotinate
      mononucleotide pyrophosphorylase or make NAD de novo. However, the inhibitor
      would mask detection of the enzyme in lung extracts. We detected a low
      nicotinatemononucleotide pyrophosphorylase-like activity (0.003 +/- 0.001
      nanomoles CO2 produced from quinolinic acid per mg of extract protein) in rat
      lung but none in foal or cow lung.

PMID- 1992283
TI  - Decrease in plasma tryptophan after a tryptophan-free amino acid solution. A
      comparison between cirrhotic and control subjects.
AB  - In healthy subjects the administration of an amino acid mixture devoid of
      tryptophan causes a marked decrease of plasma tryptophan. This is because amino
      acid mixtures induce protein synthesis and tryptophan in blood is incorporated
      into newly synthesized proteins. We hypothesized that a tryptophan-free mixture
      could differently affect plasma tryptophan levels in subjects with an impaired
      protein synthesis such as chronic liver patients. We studied tryptophan levels
      after a tryptophan-free amino acid solution in controls and cirrhotics fasting 12
      hours. Plasma total tryptophan fell to 91% of the initial level 60 minutes after
      the administration of the diet, to 71% after 120, and to 50% after 210' in
      controls. In cirrhotics the solution caused a decrease of plasma tryptophan that
      began significantly later than in controls, the delay being proportional to the
      severity of the disease. Cirrhotics were subdivided into two groups in accordance
      to the Pugh modification of the Child-Turcotte criteria. Total plasma tryptophan
      was 100% of base line levels after 60', 88% after 120', and 65% after 210' in
      less severe clinical condition; total plasma tryptophan was 102% of base line
      levels after 60', 98% after 120', and 75% after 210' in more severe clinical
      condition.

PMID- 1992284
TI  - Activation of peripheral serotonin2 receptors induces hypothermia in mice.
AB  - The effects of peripherally administered serotonin (5-HT) on the rectal
      temperature were investigated. 5-HT i.p. induced a dose-dependent hypothermia in
      mice. The hypothermic effects of 5-HT were strongly antagonized by the 5-HT1 and
      5-HT2 receptor antagonist methysergide and the 5-HT2 receptor antagonist
      ketanserin. However, the 5-HT1 receptor antagonist pindolol and the 5-HT3
      receptor antagonist ICS 205-930 were without effect. In addition, the peripheral
      5-HT2 receptor antagonist xylamidine strongly reduced 5-HT-induced hypothermia.
      These results indicate that the activation of the peripheral 5-HT2 receptors
      induces hypothermia, although the central 5-HT2 receptors have been suggested to
      relate to hyperthermia.

PMID- 1992285
TI  - Regional influences on the physical properties of T cell membranes.
AB  - Differences in the composition of membrane lipids are well documented between
      cells from distinct tissues. These differences may be manifested by changes in
      the motional freedom or fluidity of lipid molecules within plasma membranes and
      may predispose to alterations in cellular function. Regional influences on immune
      function have been implied by the finding that thymic-derived cells from murine
      spleen and lymph nodes are differentially responsive to antigen priming. The
      possibility that microenvironment also shapes the physical properties of T
      lymphocyte membranes has not been explored and is the focus of this study. Using
      mice as the experimental model, differences were found in fluidity and in the
      resting level of intracellular free-ionized Ca2+ between splenic and lymph node T
      cells from immunologically normal mice and from autoimmune-prone MRL-lpr/lpr
      mice. The results indicate that T cells are more heterogeneous than previously
      recognized and suggest a potential role for microenvironment in determining
      immune responsiveness.

PMID- 1992286
TI  - Irreversible blockade of the high and low affinity (3H) naloxone binding sites by
      C-6 derivatives of morphinane-6-ones.
AB  - C-6 derivatives--hydrazones, phenylhydrazones, dinitrophenylhydrazones, oximes
      and semicarbazones--of morphinane-6-ones were synthesized and their binding
      characteristics were studied on rat brain membranes. The dihydromorphinone and
      oxymorphone derivatives compete for the (3H)naloxone binding sites with high
      affinity, while the dihydrocodeinone and oxycodone derivatives are less potent.
      The affinity of the new compounds is decreased for the delta sites as compared to
      the parent ligands. The ligands bearing bulky substituents also bind with low
      affinity to the kappa sites. The modification decreased the Na(+)-index of
      compounds indicating their mixed agonist-antagonist character. The
      dihydromorphinone derivatives are all capable to block irreversibly the high
      affinity binding site of (3H)naloxone, whereas the dihydrocodeionone derivatives
      block irreversibly the low affinity site. A possible mechanism for the inhibition
      is suggested.

PMID- 1992287
TI  - Inhibition of pancreatic phospholipase A2 activity by uteroglobin and antiflammin
      peptides: possible mechanism of action.
AB  - We investigated the possible mechanism of inhibition of porcine pancreatic
      phospholipase A2 in vitro by rabbit uteroglobin and by the antiflammin peptides.
      We optimized the conditions of phospholipase A2 assay using a deoxycholate
      phosphatidylcholine mixed micellar substrate and established the activity of
      these inhibitors under optimized conditions. The results of fluorescence studies
      and crosslinking experiments indicate that the inhibitors interact with the
      enzyme in solution and affect the increase in intrinsic fluorescence of
      phospholipase A2 observed upon interaction with a mixed micellar substrate. In
      addition, we identified a sequence similarity between the antiflammin peptides,
      the putative active region of uteroglobin and a region in pancreatic
      phospholipase A2. This region of phospholipase A2 has been previously identified
      as being involved in the regulation of dimerization of this enzyme, and is
      conserved in the pancreatic-type enzymes. Taken together, these observations
      suggest that uteroglobin and antiflammins interact with porcine pancreatic
      phospholipase A2 and this may, at least in part, explain the enzyme inhibitory
      effect of these molecules observed in vitro. One possible mechanism of this
      effect may be an interference with the dimerization process of phospholipase A2
      which is associated with interfacial activation.

PMID- 1992289
TI  - Circadian rhythm in adenosine A1 receptor of mouse cerebral cortex.
AB  - In order to investigate diurnal variation in adenosine A1 receptors binding
      parameters, Bmax and Kd values of specifically bound N6 - cyclohexyl
      [3H]adenosine were determined in the cerebral cortex of mice that had been housed
      under controlled light-dark cycles for 4 weeks (light on from 7.00 to 19.00 h).
      Significant differences were found for Bmax values measured at 3-hr intervals
      across a 24-h period, with low Bmax values during the light period and high Bmax
      values during the dark period. The amplitude between 03.00 and 18.00 hr was 33%.
      No substantial rhythm was found in the Kd values. It is suggested that the
      changes in the density of A1 receptors could reflect a physiologically-relevant
      mechanism by which adenosine exerts its modulatory role in the central nervous
      system.

PMID- 1992288
TI  - Aortic ornithine decarboxylase activity in deoxycorticosterone/salt hypertensive
      rats.
AB  - Previous studies from our own and other laboratories have shown that hypertension
      induces changes in the growth of arterial smooth muscle cells (SMC). The purpose
      of this study was to examine the role of ornithine decarboxylase (OrnDCase) in
      this process. OrnDCase, the rate limiting enzyme in polyamine biosynthesis,
      increases in activity early in the cell cycle, and has been used as a marker of
      cell growth or proliferation. Deoxycorticosterone (DOC)/salt hypertension was
      induced in male Wistar rats. At 1-3 day intervals of DOC/salt treatment, the
      aortas were removed and OrnDCase activity and DNA content were determined. The
      results indicated that OrnDCase activity increased as early as day 2 of DOC/salt
      administration, reached a peak at day 10, and fell to a baseline by day 16. DNA
      content increased after day 10 to levels approximately 25% greater than in
      controls. Significant increases in blood pressure were not observed until after
      day 8. The findings indicate that OrnDCase activity is stimulated by DOC/salt
      even before the rise in blood pressure and that factors other than blood pressure
      per se may be important in stimulating aortic smooth muscle cell growth in the
      development of hypertension.

PMID- 1992290
TI  - Effects of kainate on glucose metabolising enzymes in the brain.
AB  - Hexokinase and glucose-6-phosphate dehydrogenase activities were studied in brain
      regions after intraventricular injection of kainic acid. Hexokinase activity was
      decreased by 10-15% in various regions while glucose-6-phosphate dehydrogenase
      activity remained unaltered. Soluble hexokinase activity, which remained the
      smaller fraction of total hexokinase activity, showed slightly more dramatic
      decreases of 15-35% compared to normal activities in brain regions. This decrease
      of hexokinase activity in the cytosolic compartment could partly account for the
      kainate-induced decreases seen in glucose metabolism.

PMID- 1992291
TI  - Bupivacaine kinetics in serum, cardiac and brain tissues: effect of diazepam
      pretreatment in mice.
AB  - This study was designed to document possible changes in bupivacaine kinetics in
      serum and in heart and brain tissues induced by a pretreatment with diazepam in
      mice. When diazepam is associated with bupivacaine, elimination of bupivacaine
      from serum and cardiac tissues is decreased; statistical differences were not
      found in brain tissues.

PMID- 1992292
TI  - Different localization of dystrophin in developing and adult human skeletal
      muscle.
AB  - Duchenne and Becker muscular dystrophy are caused by defects in dystrophin
      synthesis. Using affinity-purified polyclonal anti-dystrophin antibodies, we have
      studied immunohistochemically the subcellular localization of dystrophin in
      embryonic, fetal, and adult human skeletal muscle. In the embryonic stages
      dystrophin first appears in the sarcoplasm at the peripheral ends of the
      myotubes, immediately adjacent to the tendons, whereas in fetal stages dystrophin
      is found throughout the entire myofibers. In agreement with literature data, in
      adult muscle dystrophin expression was found to be restricted to the sarcolemma.
      The sarcoplasmic localization in embryonic and fetal tissue and the sarcolemmal
      localization of dystrophin in mature muscle suggests the accumulation of
      dystrophin in the cytoplasm prior to its integration into the membrane. These
      results increase our knowledge of the ontogenesis of dystrophin and may lead to a
      better understanding of the great diversity in pathological cases of Duchenne and
      Becker muscular dystrophy.

PMID- 1992293
TI  - Neonatal mammalian spinal cord neurons and motoneurons in monolayer culture.
AB  - Previously, embryonic tissues have been used to produce monolayer cultures
      containing mammalian spinal cord neurons (SCN) and motoneurons (MN) for studies
      of the pathophysiology of motoneuron diseases. We demonstrate here that viable
      SCN and MN were observed in dissociated cultures from neonatal rat and mouse.
      These SCN and MN produced neurites and expressed acetylcholinesterase, neuron
      specific enolase and neurofilament protein. These results indicate that cultured
      postnatal SCN and MN are capable of survival, neurite extension, and phenotypic
      expression in culture.

PMID- 1992294
TI  - Reversible myeloneuropathy of nitrous oxide abuse: serial electrophysiological
      studies.
AB  - Detailed electrophysiological studies were performed in 4 patients with
      myeloneuropathy induced by abuse of nitrous oxide for 1 to 4 years. All presented
      with paresthesias, weakness, and Lhermitte's phenomena, and exhibited signs of
      sensorimotor polyneuropathy, ataxia, and arreflexia. Two had subnormal serum
      vitamin B12 levels. Baseline electrophysiologic testing revealed reduced motor
      unit potentials, prolonged F wave latencies, absent H reflexes, denervation
      potentials, and delays in motor and sensory conduction. Three had peripheral and
      nuchal delay after median nerve stimulation. All were reevaluated after 3 to 12
      months' abstinence and treatment with vitamin B12, and all showed substantial
      clinical improvement. Parallel improvement in electrophysiologic findings
      occurred, but residual minor conduction delays, loss of H reflexes,
      electromyographic evidence of denervation, or abnormalities of posterior tibial
      SEP were noted. These findings confirm the reversibility of myeloneuropathy of
      nitrous oxide abuse and describe the profile of electrophysiologic recovery in
      subjects who abstain from further neurotoxic exposure.

PMID- 1992295
TI  - Diaphragmatic fatigue produced by constant or modulated electric currents.
AB  - In anesthetized rabbits the efficiency of phrenic nerve stimulation with trains
      of electric current was studied either when ventilation was effected entirely by
      bilateral nerve stimulation (electrophrenic ventilation) or during unilateral
      nerve stimulation when animals were ventilated with a pump and open chest. Trains
      of rectangular electric pulses (RPT) with constant amplitude and frequency or
      sine waves, both the amplitude and frequency of which were modulated and
      controlled by a computer (MSWT), were used with each animal. MSWT closely
      reproduced the physiological shape of transdiaphragmatic pressure waves.
      Diaphragm fatigue, as determined from the decrease in the maximal relaxation rate
      of twitches, occurred after 20 minutes of bilateral or unilateral nerve
      stimulation with RPT, but only after 60 min (unilateral stimulation) or 98 min
      (bilateral stimulation) with MSWT. These data show the importance of the motor
      signal pattern in long-lasting nerve stimulation.

PMID- 1992296
TI  - X-irradiation improves mdx mouse muscle as a model of myofiber loss in DMD.
AB  - The mdx mouse, although a genetic and biochemical homologue of human Duchenne
      muscular dystrophy (DMD), presents a comparatively mild histopathological and
      clinical phenotype. These differences are partially attributable to the greater
      efficacy of regeneration in the mdx mouse than in DMD muscle. To lessen this
      disparity, we have used a single dose of X-irradiation (16 Gy) to inhibit
      regeneration in one leg of mdx mice. The result is an almost complete block of
      muscle fiber regeneration leading to progressive loss of muscle fibers and their
      replacement by loose connective tissue. Surviving fibers are mainly peripherally
      nucleated and, surprisingly, of large diameter. Thus, X-irradiation converts mdx
      muscle to a model system in which the degenerative process can be studied in
      isolation from the complicating effect of myofiber regeneration. This system
      should be of use for testing methods of alleviating the myofiber degeneration
      which is common to mdx and DMD.

PMID- 1992297
TI  - Study on the erythrocytes from myotonic dystrophy with multi-nuclear NMR.
AB  - We have studied the water permeability through membranes, the function of the Na
      pump, and glucose metabolism of erythrocytes of patients with myotonic muscular
      dystrophy (MyD) using 1H--, 23Na, and 13C-NMR techniques. A significant decrease
      in water permeability was recognized in the MyD erythrocyte membrane, and
      impaired Na pumping was suspected to be correlated with the former biochemical
      abnormalities in band III protein of MyD erythrocyte membrane. Significant
      acceleration of glycolysis in the erythrocyte for the first 160 minutes was also
      recognized in MyD; however, the production of lactate showed no difference
      between MyD and controls. The increased glucose uptake in MyD may be compensatory
      to the diminished pumping mechanism, but further information, such as inorganic
      phosphate permeability and the activity of the rate-limiting enzyme of
      erythrocyte glycolysis, is needed.

PMID- 1992298
TI  - Abnormal single motor unit behavior in the upper motor neuron syndrome.
AB  - We studied the discharge pattern of single motor units (SMUs) in the left and
      right biceps muscles from a patient with nonspastic weakness of the left arm.
      Detailed statistical analysis of the behavior of discharge patterns of 4 of 4
      single motor units on the affected side showed abnormalities with characteristic
      features of an upper motor neuron lesion. Five out of 5 single motor units
      recorded from the right biceps were normal. An upper motor neuron lesion
      affecting the left arm, predicted by our results, was confirmed by magnetic
      resonance imaging (MRI), which showed a lesion in the right precentral gyrus. It
      appears that changes in single motor unit firing characteristics, caused by an
      upper motor neuron lesion, can be detected at a time when there is no evidence of
      increased "tone" and/or hyperreflexia (spasticity) in the affected extremity.

PMID- 1992299
TI  - Effects of short spaceflights on mechanical characteristics of rat muscles.
AB  - The aim of this study was to investigate the contractile protein characteristics
      after 5-day (Cosmos 1514) and 7-day (Cosmos 1667) spaceflights. The experiments
      were performed on skinned fibers from the soleus, gastrocnemius lateralis, and
      plantaris muscles isolated from Wistar rats. A reduction in fiber diameter might
      explain the decrease in the maximal tension in the soleus, whereas this tension
      was unaltered in the gastrocnemius and the plantaris. Moreover the calcium
      sensitivity of the myofilament appeared modified in the soleus and in the
      gastrocnemius: The tension/pCa relationships were shifted toward higher calcium
      concentrations, indicating a decrease in the apparent calcium binding constant of
      the troponin C. The tension/pCa relationship appeared unaltered in the plantaris
      after spaceflight. Finally, the studies of the time to reach a steady tension
      indicated an increase in the rate of force development in the soleus and, on the
      contrary, a slowing down in the plantaris. No change in the gastrocnemius was
      found. The results were analyzed with references to the different muscle
      functions in disuse atrophy.

PMID- 1992300
TI  - On the shape of the normal turns--amplitude cloud.
AB  - Factors that affect the shape of the so-called "normal cloud" of the turns and
      amplitude measurements of the electromyographic interference pattern are
      investigated. As the force of voluntary contraction increases from low to
      moderate levels, the number of turns in the signal increase faster than does the
      mean amplitude change between turns. This results in a cloud that is concave
      downward. At higher force levels, the pattern is reversed. The overall shape of
      the cloud thus depends on the maximum effort at which recordings are made, which
      is determined by the procedure of muscle activation.

PMID- 1992301
TI  - A new instrument for obtaining tissue biopsy of muscle.

PMID- 1992302
TI  - Hereditary motor and sensory neuropathy.

PMID- 1992303
TI  - Electrophysiology of acetylcholinesterase inhibition in myasthenia gravis.

PMID- 1992304
TI  - Rice-based oral electrolyte solutions for the management of infantile diarrhea.
AB  - BACKGROUND: In infants the treatment of acute diarrhea with glucose-based
      solutions results in rehydration but does not reduce the severity of diarrhea.
      Oral rehydration with solutions based on rice powder may reduce stool output as
      well as restore fluid volume. METHODS: We designed a prospective, randomized,
      double-blind study to evaluate the efficacy of two rice-based rehydration
      solutions and a conventional glucose-based solution. Solution A contained only
      rice-syrup solids, solution B contained rice-syrup solids and casein hydrolysate,
      and solution C, the glucose-based solution, served as control. The study subjects
      were 86 mildly to moderately dehydrated infant boys, 3 to 18 months old, who were
      admitted to a children's hospital with acute diarrhea. We measured fluid intake,
      fecal and urine output, and absorption and retention of fluid, sodium, and
      potassium at intervals for 48 hours in all 86 infants. RESULTS: The mean (+/- SE)
      fecal output was significantly lower in the infants given solution A (group A
      infants) than in the infants given solution C (group C) (29 +/- 4 vs. 46 +/- 7 ml
      per kilogram of body weight, P less than 0.05) during the first six hours of
      therapy. The infants in group A also had greater fluid absorption (221 +/- 16 vs.
      167 +/- 9 ml per kilogram, P less than 0.05) over the entire 48 hours of therapy
      and greater potassium absorption (1.6 +/- 0.2 vs. 0.6 +/- 0.1 mmol per kilogram,
      P less than 0.05) during the first six hours than the infants in group C.
      Solution B offered no advantages over solution A. CONCLUSIONS: Solutions
      containing rice-syrup solids were effective in the rehydration of infants with
      acute diarrhea. They decreased stool output and promoted greater absorption and
      retention of fluid and electrolytes than did a glucose-based solution.

PMID- 1992305
TI  - Aggravation of subclinical diabetes insipidus during pregnancy.
AB  - BACKGROUND: Transient polyuria and polydipsia during pregnancy are rare, and
      their cause is not entirely clear. Possible explanations include the exacerbation
      of preexisting abnormalities in the secretion or action of vasopressin and
      abnormally large increases in plasma vasopressinase activity. METHODS: We studied
      two women in whom overt polyuria and polydipsia developed during the third
      trimester of pregnancy and disappeared after delivery. The secretion and action
      of vasopressin were studied both when the women had polyuria and polydipsia and
      later, when their water intake and urine volume were normal. RESULTS: One patient
      had partial nephrogenic diabetes insipidus. She had little increase in urine
      osmolality in response to water deprivation, hypertonic-saline infusion, and
      vasopressin injection and no response to desmopressin acetate (1-deamino-8-D
      arginine vasopressin) during the immediate postpartum period. Her basal and
      stimulated plasma vasopressin concentrations were high (16.5 to 203.4 pmol per
      liter) before and during hypertonic-saline infusion 30 months post partum. The
      other patient had partial neurogenic diabetes insipidus. She had subnormal basal
      plasma vasopressin concentrations, a subnormal increase in the plasma vasopressin
      level and a subnormal decrease in urine flow in response to the administration of
      vasopressin, and a normal response to desmopressin. After pregnancy, when her
      urine volume was normal, she had no increase in plasma vasopressin in response to
      hypertonic-saline infusion, but she had a normal rise in the plasma vasopressin
      level and a normal renal response to vasopressin administration. CONCLUSIONS:
      Pregnancy may unmask subclinical forms of both nephrogenic and neurogenic
      diabetes insipidus. This exacerbation may result from both increased
      vasopressinase activity and diminished renal responsiveness to vasopressin.

PMID- 1992306
TI  - Aluminum accumulation during treatment with aluminum hydroxide and dialysis in
      children and young adults with chronic renal disease.
AB  - BACKGROUND: The control of hyperphosphatemia is a major clinical problem in
      patients with chronic renal failure receiving regular dialysis treatment. Despite
      continuing concern about aluminum toxicity, aluminum-containing antacids are
      still used in many of these patients as phosphate-binding agents. Although
      maximal acceptable doses of aluminum hydroxide have been recommended, the safety
      and efficacy of these guidelines have not been evaluated. METHODS: Seventeen
      children and young adults (mean [+/- SD] age, 14.1 +/- 3.7 years) undergoing
      regular peritoneal dialysis were randomly assigned to treatment with either
      aluminum hydroxide (n = 7; maximal dose, 30 mg per kilogram of body weight per
      day) or calcium carbonate (n = 10; dose range, 2.5 to 12 g per day, according to
      serum phosphorus levels). Aluminum retention was assessed by serial measurements
      of plasma aluminum, deferoxamine-infusion tests, and measurements of bone
      aluminum content during a mean (+/- SD) follow-up of 13 +/- 2 months. The
      evolution of bone disease was also evaluated. RESULTS: Plasma aluminum levels and
      the increment in plasma aluminum after infusion of deferoxamine increased from
      base-line values in the patients treated with aluminum hydroxide, and aluminum
      related bone disease developed in one patient. Serum phosphorus levels remained
      higher and serum calcium levels lower in the patients receiving aluminum
      hydroxide than in those receiving calcium carbonate. The skeletal lesions of
      secondary hyperparathyroidism improved in 7 of 10 patients receiving calcium
      carbonate but persisted or progressed in 6 of 7 patients given aluminum hydroxide
      (P less than 0.025). CONCLUSIONS: Aluminum hydroxide is less effective than
      calcium carbonate as a phosphate-binding agent for the control of
      hyperphosphatemia and is associated with aluminum retention in children and young
      adults with chronic renal failure who are receiving dialysis therapy.

PMID- 1992307
TI  - Board-certified physicians in the United States, 1971-1986.
AB  - BACKGROUND: This is our third report covering the census of U.S. physicians over
      a 15-year period. The present report updates the information for 1980 to 1986.
      METHODS: Most of our data are based on published information from the Association
      of American Medical Colleges, the Educational Council for Foreign Medical
      Graduates, the American Board of Medical Specialties, and the National Resident
      Matching Program. Data on board-certified physicians were obtained from the
      Division of Survey and Data Resources of the American Medical Association and are
      not published elsewhere. RESULTS: After a steep rise in the 1970s, the annual
      number of physicians receiving licenses increased at a slower rate. The numbers
      of new board diplomas in medicine and primary care continued to grow. In other
      non-surgical clinical specialties there was less growth, and in certain fields of
      surgery the numbers declined. The board-certified percentage of all practitioners
      increased slightly (74 to 79 percent). About 14 to 16 percent of all active
      physicians are still in their residency and fellowship years. The percentage of
      all practitioners under the age of 35 who are women has increased from 8.4
      percent in 1967 to 25.2 percent in 1986. The enrollment of some residency
      programs is currently more than 50 percent women. CONCLUSIONS: The work force of
      physicians did not grow as rapidly in the 1980s as in the 1970s. This
      nonlinearity of growth and massive changes in the epidemiology and treatment of
      disease render predictions about the need for or the numbers of physicians a
      decade hence unreliable.

PMID- 1992308
TI  - Successful in utero treatment of fetal goiter and hypothyroidism.

PMID- 1992309
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 8-1991. A 69-year-old man with abdominal pain six weeks after a
      coronary revascularization procedure.

PMID- 1992310
TI  - "Non-sweet" diabetes of pregnancy.

PMID- 1992311
TI  - Aluminum--much ado about something.

PMID- 1992312
TI  - Recognition of thyroid disease in the fetus.

PMID- 1992313
TI  - The Nancy Cruzan case.

PMID- 1992314
TI  - HTLV-II endemicity among Guaymi Indians in Panama.

PMID- 1992315
TI  - An ultrasound method for safe and rapid central venous access.

PMID- 1992316
TI  - A comparison of expenditures for physicians' services in the United States and
      Canada.

PMID- 1992317
TI  - Health professionals held as political prisoners in Syria.

PMID- 1992318
TI  - Twelve-year comparison of a Bjork-Shiley mechanical heart valve with porcine
      bioprostheses.
AB  - BACKGROUND: Patients undergoing heart-valve replacement may receive a mechanical
      prosthesis, necessitating lifelong anticoagulant treatment, or a porcine
      bioprosthesis, which involves no absolute need for anticoagulants. METHODS: We
      carried out a randomized, prospective trial to compare the durability of the
      Bjork-Shiley mechanical prosthesis (spherical tilting-disk model) and the
      incidence of valve-related complications with those variables in the Hancock and
      the Carpentier-Edwards porcine prostheses. The mitral valve was replaced in 261
      patients, the aortic valve in 211, and both in 61; the survivors have been
      followed up for a mean of 12 years. RESULTS: We found a trend toward improved
      actuarial survival after 12 years with the Bjork-Shiley prosthesis, but this
      trend was not statistically significant (group with Bjork-Shiley valve vs. group
      with porcine valve [mean +/- SE], 51.5 +/- 3.2 vs. 44.4 +/- 3.2 percent; P =
      0.08). There was no significant difference in the actuarial incidence of
      reoperation after 5 years, but after 12 years significantly more patients with a
      porcine prosthesis had undergone reoperation (8.5 +/- 2.0 vs. 37.1 +/- 4.1
      percent, P less than 0.001). An analysis combining death and reoperation as end
      points for an actuarial assessment of survival with the original prosthesis
      intact confirmed that the patients with Bjork-Shiley Shiley prostheses had
      improved survival (48.6 +/- 3.2 vs. 30.0 +/- 3.0 percent after 12 years, P less
      than 0.001). Bleeding requiring hospitalization or blood transfusion was
      significantly more frequent in the patients with Bjork-Shiley prostheses (18.6 +/
      3.2 vs. 7.1 +/- 2.3 percent after 12 years, P less than 0.01). There was no
      significant difference after 12 years in the actuarial occurrence of embolism
      (Bjork-Shiley vs. porcine, 21.1 +/- 3.1 vs. 26.4 +/- 3.5 percent) or endocarditis
      (3.7 +/- 1.4 vs 4.6 +/- 1.6 percent). CONCLUSIONS: Survival with an intact valve
      is better among patients with the Bjork-Shiley spherical tilting-disk prosthesis
      than among patients with porcine bioprostheses, but use of the Bjork-Shiley valve
      carries an attendant increased risk of bleeding associated with the need for
      anticoagulant treatment.

PMID- 1992319
TI  - A placebo-controlled trial of maintenance therapy with fluconazole after
      treatment of cryptococcal meningitis in the acquired immunodeficiency syndrome.
      California Collaborative Treatment Group.
AB  - BACKGROUND AND METHODS: In patients with the acquired immunodeficiency syndrome
      (AIDS), the rate of relapse after primary treatment for cryptococcal meningitis
      remains high. We conducted a controlled, double-blind trial to evaluate the
      efficacy of maintenance therapy with fluconazole. At entry into the study, all
      participants had sterile cultures of cerebrospinal fluid, blood, and urine after
      following a standardized course of therapy for culture-proved cryptococcal
      meningitis. The patients were randomly assigned to take either fluconazole or
      placebo as maintenance therapy. The dose of fluconazole was 100 mg daily in the
      first phase of study and 200 mg daily in the second phase. RESULTS: Of 84
      patients initially enrolled, 16 (19 percent) were found to have silent,
      persistent infection on the basis of cultures that became positive after entry
      into the study; 7 other patients were lost to follow-up shortly after entry. Of
      the remaining 61 patients, 10 of 27 assigned to placebo (37 percent) and 1 of 34
      assigned to fluconazole (3 percent) had a recurrence of cryptococcal infection at
      any site (difference in risk, 34 percent; 95 percent confidence interval, 15 to
      53). Of the 11 recurrent infections, 7 were detected in urine obtained after
      prostatic massage. There were four recurrent meningeal infections in the patients
      taking placebo, but none in those taking fluconazole (mean duration of follow-up,
      164 days) (P = 0.03). In multivariate analyses, the best predictors of recurrence
      free survival were fluconazole treatment (P = 0.02; relative hazard, 13.2), a
      lower serum cryptococcal-antigen titer (P = 0.05; relative hazard, 1.2), and more
      prolonged primary therapy with flucytosine (P = 0.09; relative hazard, 1.1).
      Survival and toxicity were similar in the two maintenance-treatment groups.
      CONCLUSIONS: In patients with AIDS, silent persistent infection is common after
      clinically successful treatment for cryptococcal meningitis. Maintenance therapy
      with fluconazole is highly effective in preventing recurrent cryptococcal
      infection.

PMID- 1992320
TI  - Lifetime use of nursing home care.
AB  - BACKGROUND AND METHODS: Despite the growth in the number of Americans in nursing
      homes, there are only limited data on the total amount of time that people spend
      in such facilities. We estimate the amount of time the average person spends in
      nursing homes over his or her lifetime (lifetime nursing home use), using data
      from the National Mortality Followback Survey of the next of kin of a sample of
      persons 25 years of age or older who died in 1986. On the basis of these data, we
      estimated the likelihood that Americans will use nursing home care during the
      course of their lifetimes and the total duration of such care. Current data on
      life expectancy were then used to reweight the sample to project lifetime nursing
      home use for those who became 65 years old in 1990. RESULTS: Of those who died in
      1986 at 25 years of age or older, 29 percent had at some time been residents in a
      nursing home, and almost half of those who entered a nursing home spent a
      cumulative total of at least one year there. The probability of nursing home use
      increased sharply with age at death: 17 percent for age 65 to 74, 36 percent for
      age 75 to 84, and 60 percent for age 85 to 94. For persons who turned 65 in 1990,
      we project that 43 percent will enter a nursing home at some time before they
      die. Of those who enter nursing homes, 55 percent will have total lifetime use of
      at least one year, and 21 percent will have total lifetime use of five years or
      more. We also project that more women than men will enter nursing homes (52
      percent vs. 33 percent), and among them, more women than men will have total
      lifetime nursing home use of five years or more (25 percent vs. 13 percent).
      CONCLUSIONS: Our projections indicate that over a lifetime, the risk of entering
      a nursing home and spending a long time there is substantial. With the elderly
      population growing, this has important implications for both medical practice and
      the financing of long-term care.

PMID- 1992321
TI  - New mechanisms of bacterial resistance to antimicrobial agents.

PMID- 1992322
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 9-1991. A 61-year-old Cambodian woman with recurrent bouts of
      abdominal pain and fever.

PMID- 1992323
TI  - The evolution of artificial heart valves.

PMID- 1992324
TI  - Outcomes of pregnancy in resident physicians.

PMID- 1992325
TI  - Intravenous IgG to prevent graft-versus-host disease after bone marrow
      transplantation.

PMID- 1992327
TI  - Diagnosis of toxoplasmosis in patients with AIDS by isolation of the parasite
      from the blood.

PMID- 1992326
TI  - Effect of recombinant interferon alfa on bone metastases of renal-cell carcinoma.

PMID- 1992328
TI  - Gynecomastia during omeprazole therapy.

PMID- 1992329
TI  - Blood glucose testing and federal regulations.

PMID- 1992330
TI  - Como estas, a mnemonic for the mental-status examination.

PMID- 1992331
TI  - Ethical watchdog's just desserts.
AB  - The US scientific community continues to make heavy weather of the policing of
      scientific misconduct, chiefly because federal agencies cannot act without being
      forced to be courts of law. But now there is a chance to undo one mistake.

PMID- 1992332
TI  - Court ruling put to test.

PMID- 1992333
TI  - AIDS viruses. Spectre of contamination.

PMID- 1992334
TI  - Human genome. Japan's project stalls.

PMID- 1992336
TI  - Climate change. A stop-start ocean conveyer.

PMID- 1992335
TI  - US research costs. Showdown over overheads?

PMID- 1992337
TI  - Visual perception. Why the eye doesn't shape up.

PMID- 1992339
TI  - Provenance of HIV strains.

PMID- 1992338
TI  - Vaccine development. Real and imagined dangers.

PMID- 1992340
TI  - Involvement of p34cdc2 in establishing the dependency of S phase on mitosis.
AB  - Mutants of cdc2+ can disrupt the dependency of S phase on completion of the
      previous mitosis. By changing the state of p34cdc2 it is possible to reprogramme
      a cell from entering mitosis to undergoing S phase. This leads to the proposal
      that the cell cycle can be considered a p34cdc2 cycle, and has implications for
      the evolution of life cycles.

PMID- 1992341
TI  - Vertical disparities and perception of three-dimensional shape.
AB  - The information about depth and three-dimensional shape available from the
      horizontal component of the stereo disparity field requires interpretation in
      conjunction with information about egocentric viewing distance (D). A novel
      computational approach for estimating D was proposed by Mayhew and Longuet
      Higgins, who demonstrated that the horizontal gradient of vertical disparities
      uniquely specifies the viewing distance. We have now used random dot stereograms
      in a shape judgement task to show that changes in vertical disparities have no
      effect on perceived three-dimensional shape. Changes in ocular convergence do
      alter perceived shape, suggesting substantial changes in the subjects' scaling of
      horizontal disparities. We conclude that vertical disparities are not used to
      scale disparities for viewing distance, and that extraretinal signals must be
      considered when analysing human three-dimensional shape perception.

PMID- 1992342
TI  - Two-tone distortion in the basilar membrane of the cochlea.
AB  - When humans listen to pairs of thnes they hear additional tones, or distortion
      products, that are not present in the stimulus. Two-tone distortion products are
      also known as combination tones, because their pitches match combinations of the
      primary frequencies (f1 and f2, f2 greater than f1), such as f2-f1, (n + 1)f1-nf2
      and (n + 1)f2-nf1 (n = 1, 2, 3...). Physiological correlates of the perceived
      distortion products exist in responses of auditory-nerve fibres and inner hair
      cells and in otoacoustic emissions (sounds generated by the cochlea, recordable
      at the ear canal). Because the middle ear responds linearly to sound and neural
      responses to distortion products can be abolished by damage to hair cells at
      cochlear sites preferentially tuned to the frequencies of the primary tones, it
      was hypothesized that distortion products are generated at these sites and
      propagate mechanically along the basilar membrane to the location tuned to the
      distortion-product frequency. But until now, efforts to confirm this hypothesis
      have failed. Here we report the use of a new laser-velocimetry technique to
      demonstrate two-tone distortion in basilar-membrane motion at low and moderate
      stimulus intensities.

PMID- 1992343
TI  - Raf-1 protein kinase is required for growth of induced NIH/3T3 cells.
AB  - Many growth factors regulate the cytoplasmic Raf-1 protein kinase, consistent
      with its having a central role in transduction of growth signals. The kinase is
      ubiquitously expressed and can promote proliferation, presumably in a manner
      dependent on growth-factor receptors and membrane-associated oncogenes. We have
      now examined the dependence of serum- and TPA (12-O-tetradecanoylphorbol-13
      acetate)-regulated NIH/3T3 cell growth on RAF-1 kinase to determine whether Raf-1
      is essential for receptor signalling. We inhibited Raf-1 function by expressing c
      raf-1 antisense RNA or kinase-defective c-raf-1 mutants. Antisense RNA for c-raf
      1 interferes with proliferation of normal NIH/3T3 cells and reverts raf
      transformed cells. In revertant cells, DNA replication induced by serum or TPA
      was eliminated or reduced proportionately to the reduction in Raf protein levels.
      Expression of a kinase-defective Raf-1 mutant (craf301) or a regulatory domain
      fragment (HCR) inhibited serum-induced NIH/3T3-cell proliferation and raf
      transformation even more efficiently. Inhibition by antisense RNA or craf301
      blocked proliferation and transformation by Ki- and Ha-ras oncogenes. We conclude
      that raf functions as an essential signal transducer downstream of serum growth
      factor receptors, protein kinase C and ras.

PMID- 1992344
TI  - Insertion of specific bases during DNA synthesis past the oxidation-damaged base
      8-oxodG.
AB  - Oxidative damage to DNA, reflected in the formation of 8-oxo-7
      hydrodeoxyguanosine (8-oxodG), may be important in mutagenesis, carcinogenesis
      and the ageing process. Kuchino et al. studied DNA synthesis on
      oligodeoxynucleotide templates containing 8-oxodG, concluding that the modified
      base lacked base pairing specificity and directed misreading of pyrimidine
      residues neighbouring the lesion. Here we report different results, using an
      approach in which the several products of a DNA polymerase reaction can be
      measured. In contrast to the earlier report, we find that dCMP and dAMP are
      incorporated selectively opposite 8-oxodG with transient inhibition of chain
      extension occurring 3' to the modified base. The potentially mutagenic insertion
      of dAMP is targeted exclusively to the site of the lesion. The ratio of dCMP to
      dAMP incorporated varies, depending on the DNA polymerase involved. Chain
      extension from the dA.8-oxodG pair was efficiently catalysed by all polymerases
      tested.

PMID- 1992345
TI  - Bush asks for 13 per cent extra for science.

PMID- 1992346
TI  - Gene therapy. Cancer trial starts.

PMID- 1992347
TI  - Animal experiments. MRC breach spurs reforms.

PMID- 1992348
TI  - Gulf oil spill. Big test for bioremediation.

PMID- 1992349
TI  - Ribozyme technology. Cech wins first patent.

PMID- 1992350
TI  - Radiation risks.

PMID- 1992351
TI  - The conformation of membranes.
AB  - Membranes composed of amphiphilic molecules are highly flexible surfaces that
      determine the architecture of biological systems and provide a basic structural
      element for complex fluids such as microemulsions. Physical theories have been
      developed to describe many aspects of their conformational behaviour, such as the
      preferred shapes and shape transformations of closed vesicles, and the shape
      fluctuations, random-surface configurations, and adhesion and unbinding of
      interacting membranes. Understanding of these phenomena has been much improved
      through fruitful interactions between theory and experiment.

PMID- 1992352
TI  - Requirement of the RNA helicase-like protein PRP22 for release of messenger RNA
      from spliceosomes.
AB  - The product of the yeast PRP22 gene acts late in the splicing of yeast pre
      messenger RNA, mediating the release of the spliced mRNA from the spliceosome.
      The predicted PRP22 protein sequence shares extensive homology with that of PRP2
      and PRP16 proteins, which are also involved in nuclear pre-mRNA splicing. The
      homologous region contains sequence elements characteristic of several
      demonstrated or putative ATP-dependent RNA helicases. A putative RNA-binding
      motif originally identified in bacterial ribosomal protein S1 and Escherichia
      coli polynucleotide phosphorylase has also been found in PRP22.

PMID- 1992353
TI  - Geometric phase shifts in chemical oscillators.
AB  - One of the most remarkable developments in quantum mechanics in recent years has
      been the discovery that when a system is moved adiabatically around a closed loop
      in parameter space there occurs, besides the familiar dynamical phase shift, an
      additional phase shift (sometimes referred to as 'Berry's phase') that is purely
      geometric in nature. The dynamical phase shift, which results from the variation
      of the period of the oscillatory system with the change in parameters, is
      relatively easily understood and is proportional to the time over which the
      parameter change occurs. The geometric phase shift, on the other hand, is less
      intuitive and depends on the curvature of the surface in parameter space bounded
      by the closed path, but is independent of the time taken to traverse the circuit.
      Here we present evidence for time-independent geometric phase shifts in numerical
      solutions for a model of an oscillating chemical reaction. The conditions for the
      occurrence of such shifts seem to be sufficiently general that geometric phase
      effects should be experimentally observable in essentially all chemical
      oscillators as well as in biological networks such as the brain and the central
      nervous system, where phase control is of vital importance.

PMID- 1992354
TI  - Evidence from reversal of handedness in C. elegans embryos for early cell
      interactions determining cell fates.
AB  - Many animals with overall bilateral symmetry also exhibit some left-right
      asymmetries with generally invariant handedness. Therefore, the left-right
      embryonic axis must have a consistent polarity, whose origins and subsequent
      effects on development are not understood. Caenorhabditis elegans exhibits such
      left-right asymmetries at all developmental stages. The embryonic cell lineage is
      asymmetric as well: although the animal is generally bilaterally symmetric, many
      of its contralaterally analogous cells arise from different lineages on the two
      sides of the embryo. I accomplished reversal of embryonic handedness by
      micromanipulation at the 6-cell stage, which resulted in mirror-image but
      otherwise normal development into healthy, fertile animals with all the usual
      left-right asymmetries reversed. This result demonstrates that in the 6-cell
      embryo the pair of anterior (AB) blastomeres on the right is equivalent to the
      pair on the left, and that the extensive differences in fates between lineally
      homologous derivatives of these cells on the two sides of the animal must be
      dictated by cell interactions, most of which are likely to occur early in
      embryogenesis.

PMID- 1992355
TI  - Requirement for the replication protein SSB in human DNA excision repair.
AB  - Replication and repair are essential processes that maintain the continuity of
      the genetic material. Dissection of simian virus 40 (SV40) DNA replication has
      resulted in the identification of many eukaryotic replication proteins, but the
      biochemistry of the multienzyme process of DNA excision repair is less well
      defined. One protein that is absolutely required for semiconservative replication
      of SV40 DNA in vitro is human single-stranded DNA-binding protein (SSB, also
      called RF-A and RP-A). SSB consists of three polypeptides of relative molecular
      mass 70,000, 34,000 and 13,000, and acts with T antigen and topoisomerases to
      unwind DNA, allowing the access of other replication proteins. Human SSB can also
      stimulate the activity of polymerases alpha and delta, suggesting a further role
      in elongation during DNA replication. We have now found a role for human SSB in
      DNA excision repair using a cell-free system that can carry out nucleotide
      excision repair in vitro. Monoclonal antibodies against human SSB caused
      extensive inhibition of DNA repair in plasmid molecules damaged by ultraviolet
      light or acetylaminofluorene. Addition of purified SSB reversed this inhibition
      and further stimulated repair synthesis by increasing the number of repair
      events. These results show that a mammalian DNA replication protein is also
      essential for repair.

PMID- 1992356
TI  - Solving the structure of human H ferritin by genetically engineering
      intermolecular crystal contacts.
AB  - Ferritin is important in iron homeostasis. Its twenty-four chains of two types, H
      and L, assemble as a hollow shell providing an iron-storage cavity. Ferritin
      molecules in cells containing high levels of iron tend to be rich in L chains,
      and may have a long-term storage function, whereas H-rich ferritins are more
      active in iron metabolism. The molecular basis for the greater activity of H-rich
      ferritins has until now been obscure, largely because the structure of H-chain
      ferritin has remained unknown owing to the difficulties in obtaining crystals
      ordered enough for X-ray crystallographic analysis. Here we report the three
      dimensional structure of a human ferritin H-chain homopolymer. By genetically
      engineering a change in the sequence of the intermolecular contact region, we
      obtained crystals isomorphous with the homologous rat L ferritin and of high
      enough quality for X-ray diffraction analysis. The X-ray structure of human H
      ferritin shows a novel metal site embedded within each of its four-helix bundles
      and we suggest that ferroxidase activity associated with this site accounts for
      its rapid uptake of iron.

PMID- 1992357
TI  - Assessment: positron emission tomography. Report of the Therapeutics and
      Technology Assessment Subcommittee of the American Academy of Neurology.

PMID- 1992358
TI  - Young-onset Parkinson's disease: a clinical review.
AB  - Young-onset Parkinson's disease (YOPD) is arbitrarily defined as that which
      produces initial symptoms between the ages of 21 and 39, inclusive. The special
      problems and concerns of the patient with YOPD present as much of a challenge and
      opportunity for the clinician as the disease itself does for the researcher. In
      contrast to juvenile parkinsonism, which is a heterogeneous group of
      clinicopathologic entities presenting (also arbitrarily) before age 21, YOPD
      appears to be the same nosologic entity as older-onset PD. It comprises
      approximately 5% of referral populations in Western countries and about 10% in
      Japan. Its annual incidence relative to the population at risk is about 1/10 that
      of PD at age sixty. YOPD tends to have more gradual progression of parkinsonian
      signs and symptoms, earlier appearance of levodopa-related dyskinesias and
      levodopa-dose-related motor fluctuations, and frequent presence of dystonia as an
      early or presenting sign. Studies conflict with regard to the suspected greater
      familial frequency and lesser frequency of dementia than in older-onset PD.

PMID- 1992359
TI  - The visceral organ brain: implications for the pathophysiology of vascular head
      pain.

PMID- 1992360
TI  - Question-driven technology assessment: SPECT as an example.

PMID- 1992361
TI  - HTLV-I-associated myelopathy associated with blood transfusion in the United
      States: epidemiologic and molecular evidence linking donor and recipient.
AB  - Six months after receiving 58 units of blood components, a 65-year-old white man
      from New York City, with no other risk factors for human T-lymphotropic virus
      type I (HTLV-I) infection, developed HTLV-I-associated myelopathy/tropical
      spastic paraparesis (HAM/TSP). Investigation of blood donors identified a 25-year
      old white Hispanic woman from Florida whose platelets had been given to the
      patient and who was seropositive for the virus on a serum specimen obtained 2
      years after the donation. She was born in Cuba and had had 2 sexual relationships
      with men who either had been born in or had resided in the Caribbean. Polymerase
      chain reaction (PCR) studies of peripheral blood mononuclear cells indicated that
      both donor and recipient were infected with HTLV-I. Molecular studies of a 595
      nucleotide sequence in the 5' envelope region of HTLV-I indicated that the
      viruses from donor and recipient were identical in each of 32 positions in which
      published HTLV-I sequences demonstrate molecular heterogeneity; the donor and
      recipient viruses were also identical in 2 additional positions in which they
      differed from all published sequences. Transfusion-associated HAM/TSP has
      occurred in the United States, but additional cases should be prevented by
      screening blood donations for HTLV-I. Molecular studies of HTLV-I may prove
      useful in defining the genetic heterogeneity of HTLV-I isolates in the United
      States and in studying transmission of this virus.

PMID- 1992362
TI  - Early development of levodopa-induced dyskinesias and response fluctuations in
      young-onset Parkinson's disease.
AB  - We evaluated whether patients with young-onset Parkinson's disease (PD) (onset
      between 21 and 40 years) develop levodopa-induced dyskinesias and motor response
      fluctuations more frequently and earlier than patients with older-onset PD (onset
      after 40 years) by determining the period from levodopa introduction to
      development of dyskinesias or fluctuations in 25 young-onset (mean age at onset,
      33.54 years) and in 25 matched older-onset PD patients (mean age at onset, 55.76
      years). Young-onset PD patients had significantly higher frequency for both
      dyskinesias and fluctuations after both 3 and 5 years of levodopa. Young-onset PD
      patients also developed both levodopa-induced dyskinesias and fluctuations
      earlier than older-onset PD patients. We suggest that the introduction of
      levodopa therapy in patients with young onset PD should be postponed as long as
      possible.

PMID- 1992363
TI  - Signs of cognitive change in HIV disease: an event-related brain potential study.
AB  - We recorded event-related brain potentials (ERPs) from 2 groups of human
      immunodeficiency virus (HIV)-positive men with no physical illness or neurologic
      involvement: 9 asymptomatic (AS+) and 9 classified as having either acquired
      immunodeficiency syndrome (AIDS; 7) or AIDS-related complex (ARC; 2). In separate
      choice reaction time tasks, the subjects pressed buttons to randomly presented
      auditory or visual stimuli at probabilities of either 20/80 or 50/50. There were
      no group differences on any of the neuropsychological tests commonly used in
      screening batteries for HIV patients. In contrast, reduced P300 amplitudes and
      increased P300 latencies occurred in ARC/AIDS patients in response to both
      auditory and visual stimuli, while in AS+ patients such alterations occurred only
      in the visual modality. Significant delays in P2 latency were found only in the
      auditory modality and then only in ARC/AIDS patients. ARC/AIDS patients alone
      showed delayed response times, and only in the auditory modality. The P300
      results demonstrate alterations in stimulus evaluation and processing speed in
      the earliest stages of HIV disease, even before cognitive deficits can be
      detected by more traditional measures.

PMID- 1992364
TI  - Delayed-onset dystonia due to perinatal or early childhood asphyxia.
AB  - We report 10 patients with delayed-onset dystonia associated with perinatal
      asphyxia and 2 associated with asphyxia in childhood. In the perinatal group, the
      mean age of onset was 12.9 years. Among these patients, dystonia continued to
      progress for a mean of 7 years, and as long as 28 years. These patients had
      moderate motor disability; none was wheelchair-bound, and thus their prognosis
      was better than that of the childhood-onset idiopathic torsion dystonias. The
      most frequently beneficial drugs were anticholinergics. Since some of these
      patients closely resembled cases of idiopathic torsion dystonia, the prior
      occurrence of asphyxia should be used as a criterion of exclusion for that
      diagnosis.

PMID- 1992365
TI  - Patient perception of tics and other movement disorders.
AB  - To determine the subjective perception patients have of abnormal movements, 170
      patients with various hyperkinesias were interviewed with questions directed at
      the "voluntary" or intentional versus "involuntary" aspects of their symptoms.
      One hundred and two of 110 patients with non-tic disorders thought that the
      abnormal movements were entirely involuntary. Forty-one of 60 tic disorder
      patients stated that all their motor and phonic tics were intentionally produced.
      Fifteen others had both voluntary and involuntary components, usually with the
      former predominating. A "voluntary" response could be used to predict the correct
      diagnostic category (tic versus non-tic) in 8 of 9 patients for whom the referral
      category was incorrect. These results suggest that a large proportion of the
      motor and phonic symptoms experienced by tic patients are irresistibly but
      purposefully executed, more akin to compulsions than to the other "involuntary"
      hyperkinesias with which they are commonly discussed.

PMID- 1992366
TI  - Hashimoto's encephalopathy: a steroid-responsive disorder associated with high
      anti-thyroid antibody titers--report of 5 cases.
AB  - We describe 5 patients with a relapsing encephalopathy in association with
      Hashimoto's disease and high titers of anti-thyroid antibodies. The presentation
      is usually with a subacute onset of confusion, alteration in conscious level, and
      focal or generalized seizures. The relapsing course, association with myoclonus
      or tremulousness, and episodes of stroke-like deterioration are characteristic
      features. The long-term prognosis is favorable with steroid therapy, though
      additional immunosuppressive therapy may be required. Neurologic investigation
      typically shows a diffusely abnormal EEG, high CSF protein level without
      pleocytosis, and normal brain CT and cerebral angiogram. Isotope brain scan may
      show patchy abnormal uptake. Hashimoto's encephalopathy should be recognized as a
      definite neurologic entity and added to the list of CNS complications of thyroid
      disease.

PMID- 1992367
TI  - Essential tremor: clinical correlates in 350 patients.
AB  - To study the demographic and clinical correlates of essential tremor (ET), we
      analyzed a comprehensive database of 350 patients evaluated at the Movement
      Disorders Clinic at Baylor College of Medicine from 1982 to 1989. The age at
      onset of tremor showed bimodal distribution for both male and female patients,
      with peaks in 2nd and 6th decades. ET appeared most frequently in hands, followed
      by head, voice, tongue, leg, and trunk. Half of the patients (47%) had associated
      dystonia, including cervical dystonia, writer's cramp, spasmodic dysphonia, and
      cranial dystonia, and 20% of the patients had associated parkinsonism. At least
      one 1st-degree relative of 62.5% of ET patients reported tremor. Alcohol relieved
      tremor in 2/3 of ET patients. Sixty-eight percent of patients who had adequate
      follow-up improved with propranolol, and 72% with primidone. There was no
      significant difference in various clinical variables between the 219 patients
      with familial ET and 131 with sporadic ET. Patients with early-onset ET were more
      likely to have hand involvement and associated dystonia than patients with late
      onset ET. Dystonia was more frequently associated with mild ET than with severe
      ET. Patients with low-frequency tremor were older and had more head but less hand
      involvement than patients with high-frequency tremor. The lack of relevant
      differences between ET subgroups suggests that, despite variable expression, ET
      represents a single disease entity.

PMID- 1992368
TI  - Symptoms and disease associations in idiopathic intracranial hypertension
      (pseudotumor cerebri): a case-control study.
AB  - To identify the symptoms and coexisting medical conditions associated with
      idiopathic intracranial hypertension (IIH), we administered an 83-item
      questionnaire at the time of diagnosis to 50 IIH patients and 100 aged-matched
      controls. Ninety percent of the IIH patients were women; the mean age was 33.
      Obesity and recent weight gain were much more common among patients than
      controls. Symptoms most commonly reported by IIH patients were headache (94%),
      transient visual obscurations (TVO) (68%), and intracranial noises (ICN) (58%).
      Daily occurrence of these symptoms was much more common among patients than
      controls. Controls also reported these and other IIH symptoms, but at lower
      frequencies. Several conditions previously associated with IIH were no more
      common in patients than controls including iron deficiency anemia, thyroid
      disease, pregnancy, antibiotic intake, and use of oral contraceptives. We
      conclude that previous studies of IIH, mostly uncontrolled and retrospective,
      have underestimated the frequency of symptoms in IIH patients and reported chance
      and spurious associations with common medical conditions and medications. The
      profile of a young obese woman with headaches and either TVO or ICN should alert
      the clinician to the diagnosis of IIH, especially when the symptoms occur daily.

PMID- 1992369
TI  - Lateral medullary infarction: prognosis in an unselected series.
AB  - We describe the acute and long-term prognosis in 43 patients with lateral
      medullary infarction (LMI) collected from a population-based stroke registry from
      1982 to July 1988. Mean age was 63.9 years and median time of follow-up was 33
      months. In the acute phase, 5 patients (11.6%) died from respiratory and
      cardiovascular complications and 2 new strokes occurred, both in the posterior
      circulation. During follow-up, recurrent vertebrobasilar territory strokes
      occurred in only 2 patients (a rate of 1.9% per year). The mechanisms of stroke
      were vertebral artery (VA) branch occlusion, causing a medial medullary syndrome,
      and basilar artery thrombosis propagating from a contralateral, distal VA
      stenosis. In the acute phase of LMI, respiratory and cardiovascular events,
      presumably caused by autonomic dysfunction related to the lateral medullary
      lesion, are the major hazards. Recurrent posterior circulation strokes were
      uncommon during follow-up.

PMID- 1992370
TI  - Infarction in the anterior rostral cerebellum (the territory of the lateral
      branch of the superior cerebellar artery).
AB  - We report 9 patients with an isolated infarct of the anterior part of the rostral
      cerebellum, ie, the territory of the lateral branch of the superior cerebellar
      artery. Clinicoanatomic correlations are based on CT, MRI, or both in 8 patients
      and on pathologic data in the ninth. The main clinical features were ipsilateral
      dysmetria and axial lateropulsion, dysarthria, and unsteadiness. In 1 patient,
      the clinical presentation mimicked a lacunar stroke (dysarthria and clumsy hand
      syndrome). There were no edematous cerebellar infarcts with signs of brainstem
      compression, and all patients spontaneously improved without significant
      sequellae. Angiography in 2 patients and pathologic examination of arteries in 1
      patient disclosed no occlusion in the vertebrobasilar system. Six patients had a
      cardiac source of emboli. In conclusion, infarcts of the anterior part of the
      rostral cerebellum can be regarded as a benign condition in which there is,
      frequently, a cardiac source of emboli.

PMID- 1992371
TI  - Myotonic heart disease: a clinical follow-up.
AB  - We followed 37 patients with myotonic dystrophy for a mean of 6 years. Two
      developed atrial flutter or fibrillation, 6 developed a new bundle branch block,
      1 developed complete heart block requiring a pacemaker, and another with
      progressive 1st-degree heart block and a widening QRS interval had a sudden
      death. Most patients had predictable, gradually progressive disease of their
      cardiac conduction system. We recommend that patients with progressive
      atrioventricular block or widening QRS interval due to myotonic heart disease
      have yearly ECGs and be questioned about syncope or presyncope to determine the
      need for a cardiac pacemaker.

PMID- 1992372
TI  - Detection of tuberous sclerosis in parents by magnetic resonance imaging.
AB  - We performed a detailed physical examination and MRI without gadolinium DTPA
      contrast in 60 couples with at least 1 child having tuberous sclerosis (TS).
      Eight parents had TS diagnosed by physical examination, family history, or
      various diagnostic procedures including MRI. Eight additional subjects and 6
      control subjects had nonspecific high-signal white matter changes on MRI. MRI
      confirmed the diagnosis of TS in only 1 parent without physical findings of the
      disease, similar to the results of earlier studies using computed cranial
      tomography. CT may be less sensitive than MRI but is probably more specific for
      TS. Either CT or MRI may occasionally help substantiate the diagnosis of TS in a
      parent with few other findings. Both studies may need to be done in some parents
      to maximize the accuracy of genetic counseling.

PMID- 1992373
TI  - Epidermal nevus syndrome: a neurologic variant with hemimegalencephaly, gyral
      malformation, mental retardation, seizures, and facial hemihypertrophy.
AB  - The epidermal nevus syndrome (ENS) is a sporadic neurocutaneous disorder that
      consists of epidermal nevi and congenital anomalies involving the brain and other
      systems. From among over 60 patients with ENS presenting with neurologic
      manifestations, we identified 17 who had hemimegalencephaly based on pathologic
      or radiologic studies. Associated brain and neurologic abnormalities included
      gyral malformations in 12 of 12, mental retardation in 13 of 14, seizures in 16
      of 17 (including 9 with infantile spasms), and contralateral hemiparesis in 7 of
      12. All had ipsilateral epidermal nevi of the head, and several had ipsilateral
      facial hemihypertrophy. We concluded that these abnormalities comprise a
      recognizable neurologic variant of ENS that we believe represents the full
      expression of primary brain involvement. Several patients also had evidence of
      acquired brain lesions such as infarcts, atrophy, porencephaly, and
      calcifications, which are best explained by prior ischemia or hemorrhage. Given
      repeated observations of blood vessel anomalies in ENS patients, we hypothesize
      that underlying vascular dysplasia predisposes to these acquired lesions. The
      same cause may be invoked to explain the wide variety of neurologic symptoms
      reported in ENS patients without hemimegalencephaly. While the cause of ENS
      remains unknown, several observations suggest a somatic mutation.

PMID- 1992374
TI  - Comparison of functional and structural brain disturbances in Wilson's disease.
AB  - We assessed the functional and structural brain disturbances in Wilson's disease
      (WD) by evoked potentials (EPs) and magnetic resonance imaging (MRI). All the 25
      neurologically symptomatic and 44% of the 16 asymptomatic patients, assessed by
      both EPs (n = 48) and imaging (n = 41), had at least 1 abnormality of either
      prolonged EP conduction times, imaging-outlined presence of cerebral lesions, or
      brain atrophy. Our findings indicate that EPs and MRI are sensitive techniques
      for the evaluation of brain involvement in WD.

PMID- 1992375
TI  - Vascular abnormalities in epidermal nevus syndrome.
AB  - We report a patient with epidermal nevus syndrome and right hemispheric infarct
      and review 3 others with neurologic manifestations best explained by ischemia or
      hemorrhage. Each had a significant vascular abnormality such as occlusion or
      blood vessel dysplasia. None had hemimegalencephaly. We hypothesize that
      underlying vascular dysplasia is the cause of the neurologic lesions in these
      patients.

PMID- 1992376
TI  - Percutaneous aspiration of brain tumor cysts via the Ommaya reservoir system.
AB  - We performed percutaneous aspiration of 21 brain tumor cysts in 20 patients using
      the Ommaya reservoir system. Ages ranged from 3 to 70 years, median 48. Sixteen
      were primary tumors (12 anaplastic glioma, 2 craniopharyngioma, 1
      oligodendroglioma, 1 brainstem glioma) and 4 were metastatic. Fourteen had the CT
      appearance of a true cyst and 7 a pseudocyst. We placed 18 catheters through
      twist drill holes via CT stereotactic guidance and 3 through burr holes via CT
      guidance and effectively aspirated 3 to 50 ml cyst fluid from 1 to 18 times in
      each patient. Postaspiration CT showed complete or significant reduction in cyst
      size in all patients in whom it was performed (18 after initial aspiration and 9
      after subsequent aspirations). Asymptomatic intracyst hemorrhage occurred in 2
      patients after cyst wall biopsy and catheter placement. There have been no other
      complications at follow-up of 4 to 114 weeks. In our experience, tumor cyst
      aspiration by the Ommaya reservoir system is as effective as percutaneous needle
      aspiration, but after catheter placement aspiration can be performed with minimal
      technical skill, avoiding repeated CT guidance required for needle aspiration of
      recurrent deep-seated cysts.

PMID- 1992377
TI  - Acquired pendular nystagmus in toluene addiction.
AB  - We studied the ocular motor abnormalities in 4 patients chronically addicted to
      sniffing glue containing toluene. They showed acquired pendular nystagmus with
      horizontal and vertical components. One patient also showed saccadic
      oscillations. The pendular nystagmus may be a manifestation of a disturbance in
      brainstem-cerebellar connections secondary to the toxic effect of toluene on
      white matter.

PMID- 1992378
TI  - Reciprocal inhibition between forearm muscles in spastic hemiplegia.
AB  - We studied reciprocal inhibition of H-reflexes in the forearm flexor and extensor
      muscles in 14 patients with spastic hemiplegia secondary to a focal cerebral
      lesion and 14 normal volunteers. In the spastic limb, the Hmax/Mmax ratio was
      increased in both flexor and particularly extensor wrist muscles. The 3 normal
      inhibitory phases of reciprocal inhibition between extensor and flexor forearm
      muscles were markedly reduced on the spastic side of patients. The early
      disynaptic phase showed the greatest alteration. Reduced or absent inhibition
      between forearm muscles associated with increased spinal motoneuron excitability
      may be typical to spastic hemiplegia.

PMID- 1992379
TI  - Interictal spiking during wakefulness and sleep and the localization of foci in
      temporal lobe epilepsy.
AB  - We examined variations in interictal spiking during sleep and wakefulness to
      assess differences in reliability for localizing epileptic foci. Forty patients
      were studied prospectively. Spikes were assessed for rates, field, and appearance
      of new foci. Final localization was determined by surgery, electrocorticography,
      and seizure onset. Comparison of interictal EEG foci with final localization was
      made. In 39 patients, slow-wave sleep activated spiking compared with
      wakefulness. Most patients showed maximal spiking in sleep stages 3 or 4.
      Restriction of field in rapid eye movement (REM) sleep and wakefulness, and
      extension of field in slow-wave sleep occurred. New foci appeared in non-rapid
      eye movement sleep in 53% of patients. Similar but not identical spiking rates,
      foci, and field distributions were seen in wakefulness and REM sleep. All REM
      foci were unilateral. Our findings suggest that localization of the primary
      epileptogenic area is more reliable in REM sleep than in wakefulness, and in
      wakefulness more than in slow-wave sleep.

PMID- 1992380
TI  - A 21-aminosteroid inhibits stimulated monocyte hydrogen peroxide and
      chemiluminescence measurements from MS patients and controls.
AB  - Monocytes are recruited to active sites of multiple sclerosis (MS) demyelination
      and may promote local tissue injury by generating an inflammatory response,
      mediated in part by the production of toxic oxygen metabolites. Corticosteroids
      are frequently and effectively used to ameliorate MS exacerbations, despite
      inadequate knowledge about the mechanism. We assessed the effects of a 21
      aminosteroid, U74500A, a new class of steroid derivatives without glucocorticoid
      or mineralocorticoid effects, on the production of hydrogen peroxide (H2O2) and
      chemiluminescence by stimulated monocytes harvested from 8 stable MS patients and
      age- and sex-matched controls. H2O2 measurements and chemiluminescence were
      significantly reduced in both groups by U74500A. These results demonstrate that
      21-aminosteroids reduce production of toxic oxygen metabolites by monocytes and
      thus their inflammatory potential, suggesting that these agents may be
      potentially effective and safe treatment for MS exacerbations.

PMID- 1992381
TI  - The effect of flunarizine on essential tremor.
AB  - We investigated the effect of flunarizine treatment (10 mg/d) in 17 subjects with
      essential tremor in a double-blind placebo-controlled design. Tremor was assessed
      by clinical scoring, tremographic recordings, and subjective rating by subjects.
      Of the 15 subjects who completed the study, 13 showed improvement. We conclude
      that flunarizine is effective treatment for essential tremor.

PMID- 1992382
TI  - Phenytoin toxicity due to interaction with clobazam.
AB  - The benzodiazepine antiepileptic drug clobazam can be added to existing AED
      treatment, usually without clinical toxicity. We report 3 patients in whom the
      addition of clobazam led within several weeks to clinically obvious phenytoin
      (PHT) intoxication in patients who had been taking maximum tolerable PHT doses.
      Symptoms and high PHT levels resolved with lowering the PHT dose. Clobazam and
      norclobazam levels were not elevated. This interaction is probably related to
      interference with hepatic degradation of PHT. Clinicians should be aware of
      possible PHT intoxication in patients starting clobazam.

PMID- 1992383
TI  - Cerebral air embolism treated by pressure and hyperbaric oxygen.
AB  - We used pressure and hyperbaric oxygen to treat 2 patients with cerebral air
      embolism, occurring as the result of invasive medical procedures, and neither
      suffered any permanent damage detectable by clinical examination and MRI. This
      outcome contrasts with reports of infarct and disability among untreated victims
      of air embolism.

PMID- 1992384
TI  - A case of myelinoclastic diffuse sclerosis in an adult.
AB  - We report a case of rapidly progressive cerebral demyelinating disease in a
      previously healthy 40-year-old woman. This case satisfies the diagnostic criteria
      for myelinoclastic diffuse sclerosis (MDS), but is unusual in the age of onset.
      This is the 1st case of MDS in an adult with full documentation of clinical,
      biochemical, radiographic, and pathologic features.

PMID- 1992385
TI  - Eosinophilia-myalgia syndrome associated with ingestion of L-tryptophan: muscle
      biopsy findings in 4 patients.
AB  - Muscle biopsies of 4 patients with the eosinophilia-myalgia syndrome associated
      with ingestion of L-tryptophan showed lymphocytic infiltrates with occasional
      eosinophils largely restricted to interstitial fibrous tissue and perivascular
      areas. There was inflammation and fibrosis of muscle spindle capsules in 3
      patients. In the 2 sickest patients, there was profound muscle atrophy, affecting
      both muscle fiber types.

PMID- 1992386
TI  - Cerebrospinal fluid eicosanoid levels: endogenous PGD2 and LTC4 synthesis by
      antigen-presenting cells that migrate to the central nervous system.
AB  - We analyzed CSF from patients with multiple sclerosis, patients with other
      neurologic diseases, and healthy controls for the presence of prostaglandin (PG)
      E2, F2 alpha, D2, I, A, and leukotriene (LT) C4. Control CSF had little
      measurable PGs or LTs. CSF eicosanoids from patients with progressive MS were
      increased. We found PGD2 only in MS CSF. CSF monocytes from patients in active
      disease produced significantly increased PGD, PGE, and LTC4 than paired
      peripheral blood monocytes and monocytes from healthy controls. We saw no
      significant difference in LTC4 production between MS and control peripheral blood
      monocytes.

PMID- 1992387
TI  - The "numb cheek-limp lower lid" syndrome.
AB  - A patient developed isolated numbness, 1st confined to the lateral nose and upper
      lip, but later involving the cheek, lower lip, upper gingiva, and the palate.
      This numbness was later associated with paresis of the muscles of the upper lip
      and angle of the mouth and with ipsilateral lower lid droop (the "numb cheek-limp
      lower lid" syndrome). Squamous cell carcinoma was discovered infiltrating the
      infraorbital nerve and distal branches of the facial nerve. Cheek numbness
      associated with lower eyelid or upper lip weakness may herald a neoplasm
      affecting the infraorbital nerve and distal facial nerve branches.

PMID- 1992388
TI  - Changing mortality from Parkinson's disease.

PMID- 1992389
TI  - Hypothermia does not explain MK-801 neuroprotection in a rat model of neonatal
      hypoxic-ischemic encephalopathy.

PMID- 1992390
TI  - Headache, third nerve palsy, and MS.

PMID- 1992391
TI  - ALS and paraproteinemia.

PMID- 1992392
TI  - EDSS reliability.

PMID- 1992393
TI  - Nifedipine in the treatment of severe preeclampsia.
AB  - We conducted a randomized clinical trial in which patients with severe
      preeclampsia between 26-36 weeks of gestation received either nifedipine (10-30
      mg sublingually, then 40-120 mg/day orally; N = 24) or hydralazine (6.25-12.5 mg
      intravenously, then 80-120 mg/day orally; N = 25). Effective control of blood
      pressure was achieved with nifedipine in 95.8% of subjects and with hydralazine
      in 68%, a statistically significant difference (P less than .05). Maternal side
      effects were minor in both groups. Acute fetal distress developed in one
      nifedipine subject and in 11 treated with hydralazine. Mean prolongation of
      gestation was 15.5 +/- 10 days with nifedipine and 9.5 +/- 11 days with
      hydralazine, a difference that did not reach statistical significance (P less
      than .07). Infants born to women treated with nifedipine were delivered at more
      advanced gestational ages (34.6 +/- 2.3 versus 33.6 +/- 2.4 weeks; statistically
      not significant), weighed more (1826 +/- 456 versus 1580 +/- 499 g; statistically
      not significant), and tended to have fewer, mainly minor, complications. The
      average number of days spent in the neonatal intensive care unit was
      significantly lower in the nifedipine group (15.1 versus 32.7 days; P less than
      .005), leading to an average 31% reduction in total (maternal and neonatal)
      hospitalization-related charges for each nifedipine-treated pregnancy. We
      conclude that nifedipine is an effective, convenient, and low-cost treatment for
      patients with severe preeclampsia, and is not associated with undesirable side
      effects.

PMID- 1992394
TI  - Catecholamine levels in pregnant physicians and nurses: a pilot study of stress
      and pregnancy.
AB  - As a pilot study of occupational stress and pregnancy, we measured urinary
      catecholamine excretion in ten pregnant physicians and three intensive care
      nurses between 26-37 weeks' gestation, once during a work day and again during a
      non-work day. Urinary catecholamines were increased by 58% (P less than .03)
      during work periods compared with non-work periods. Catecholamine levels were
      also increased by 64% (P less than .025) over those of a working non-physician
      control group of similar gestational age. Urinary catecholamine levels are a
      direct reflection of plasma catecholamine levels. Catecholamine levels are known
      to increase with physical stress, such as standing, and with mental stress, such
      as difficult problem-solving. Catecholamines are also known to decrease uterine
      blood flow. Measurement of catecholamines may be a helpful marker in
      investigating the relationship between occupation and pregnancy outcome.

PMID- 1992395
TI  - Etiologies of preterm birth in an indigent population: is prevention a logical
      expectation?
AB  - To assess the expectations of preterm birth prevention, we determined the causes
      of preterm birth in a population of indigent women. We studied 13,119 singleton
      births in a predominantly black, indigent population occurring between November
      1982 and April 1986 to identify the proportion of preterm births that may have
      been prevented using current treatment modalities. Forty-four percent of the
      preterm births occurred at 35 to 36 weeks' gestational age, a time when most
      practitioners do not attempt tocolysis. Of the remainder, 17% occurred before 35
      weeks but were indicated for maternal medical or obstetric complications, and
      another 17% occurred before 35 weeks but followed spontaneous premature rupture
      of the membranes. Therefore, of the 1445 preterm births, we calculated that only
      336 (23.2%) were theoretically preventable. A fourth of these presented at less
      than 3 cm cervical dilatation and were treated appropriately with tocolytics, but
      delivered anyway. Therefore, most of the potentially preventable births occurred
      in the group that presented with cervical dilatation of more than 3 cm. We
      conclude that improving the preterm birth rate significantly below current levels
      may be difficult to achieve.

PMID- 1992396
TI  - Patient-controlled epidural analgesia during labor.
AB  - This study compared the safety, efficacy, local anesthetic usage, patient
      satisfaction, and anesthesia manpower demands of patient-controlled epidural
      analgesia and continuous epidural infusion during labor. After establishment of
      epidural analgesia, 88 parturients with vertex presentation were assigned
      randomly to receive either patient-controlled epidural analgesia or continuous
      epidural infusion, using 0.125% bupivacaine containing 1 microgram/mL of
      fentanyl. Inadequate analgesia was treated in both groups with a 10-mL "top-up"
      of 0.25% bupivacaine. Patients receiving patient-controlled epidural analgesia
      required significantly fewer supplemental top-up doses (36 versus 71%; P less
      than .05) and insignificantly less local anesthetic (13.6 +/- 0.6 versus 14.6 +/-
      0.5 mL/hour; P = .10). The two groups did not differ in incidence of hypotension,
      high sensory blockade (above T8), mode of delivery, or patient satisfaction
      assessed by questionnaire. Use of local anesthetic solution was examined with
      respect to cervical dilatation and did not increase late in labor. Patients
      generally viewed infusion technology favorably. These findings suggest that
      patient-controlled epidural analgesia is safe and effective, reduces anesthesia
      manpower needs, and is well accepted.

PMID- 1992397
TI  - Risk factors for shoulder dystocia: an engineering study of clinician-applied
      forces.
AB  - We report on engineering risk factors associated with clinician-applied forces
      during vaginal delivery of newborns. Specifically, we present and interpret data
      from a series of experiments using force-sensing devices on 29 randomly selected
      vaginal births, including two shoulder dystocia deliveries and one birth injury.
      The results indicate that clinician-applied peak forces are typically about 47 N
      for routine deliveries, 69 N for difficult deliveries, and 100 N for a shoulder
      dystocia delivery (P less than .01). The time required to deliver fetal shoulders
      doubles for nonroutine deliveries (P less than .01). In addition, impulse and
      rate of application of force distinguish between routine and nonroutine
      deliveries (P less than .03). We conclude that, if properly perceived, force,
      force rate, and the duration of force are objective parameters that can be used
      in recognizing and managing shoulder dystocia and in predicting thresholds for
      birth injury.

PMID- 1992398
TI  - Validation of the 1988 ACOG forceps classification system.
AB  - In February 1988, an ACOG Committee Opinion substantially revised the
      classification of forceps operations. The revision addressed two significant
      shortcomings of the old system: Outlet forceps had been defined too narrowly and
      midforceps too imprecisely. We now report the results of a prospective study of
      357 forceps deliveries classified using each system. Allowing up to 45 degrees of
      rotation in an outlet forceps delivery did not increase morbidity measured by any
      criterion. Dividing the old midforceps group by precisely identifying station and
      rotation permitted greater stratification of the risks of short-term neonatal and
      maternal morbidity. We conclude that our results validate the 1988 classification
      scheme.

PMID- 1992399
TI  - Brain growth among fetuses exposed to cocaine in utero: asymmetrical growth
      retardation.
AB  - Fetal growth retardation may be associated with maternal cocaine use during
      pregnancy. The pattern of fetal growth retardation was analyzed in infants born
      to 80 women who used cocaine, but not alcohol, during pregnancy, and in two
      comparison groups: 100 infants born to mothers who used neither alcohol nor
      cocaine during pregnancy and 67 infants whose mothers used alcohol but not
      cocaine during pregnancy. There were statistically significant differences in
      head size between the unexposed and cocaine-exposed infants (P less than .001).
      Notably, head circumference was reduced proportionately more than birth weight in
      cocaine-exposed infants, a pattern similar to that observed in alcohol-exposed
      infants. Alcohol- and cocaine-exposed infants were not statistically different in
      head circumference. We conclude that brain growth of cocaine-exposed infants is
      similar to that reported for alcohol-exposed infants, and that cocaine-exposed
      infants may be characterized as having asymmetrical growth retardation.

PMID- 1992400
TI  - Transvaginal color Doppler assessment of the uteroplacental circulation in early
      pregnancy.
AB  - Transvaginal color Doppler was used to investigate the uteroplacental circulation
      of 45 patients with normal intrauterine pregnancies at 4-18 weeks' gestation. The
      main uterine artery and the radial and spiral arteries were demonstrated, and
      characteristic flow velocity waveforms were obtained in more than 90% of cases.
      The indices of impedance to flow decreased with gestation and there was a
      progressive fall in these indices from the uterine artery, through the radial, to
      the spiral artery. Blood velocity in the uterine artery increased exponentially
      with gestation.

PMID- 1992401
TI  - Fetal renal artery velocity waveforms and amniotic fluid volume in growth
      retarded and post-term fetuses.
AB  - Renal blood flow velocity waveforms were recorded by Doppler ultrasonography in
      114 growth-retarded fetuses and in 97 post-term fetuses. The pulsatility index
      (PI) values were compared with our reference limits for gestational age and
      related to the amount of amniotic fluid. Growth-retarded fetuses showed
      significantly increased PI values compared with normally grown fetuses, and this
      difference was particularly evident in cases of oligohydramnios. Furthermore,
      there was a significant negative correlation between the increase in PI and the
      amniotic fluid volume. Post-term fetuses showed no significant differences in PI
      values compared with term fetuses and no significant correlation between the
      amount of amniotic fluid and PI values.

PMID- 1992402
TI  - Diverse maternal and fetal pathology associated with absent diastolic flow in the
      umbilical artery of high-risk fetuses.
AB  - Twenty-two of approximately 450 high-risk pregnancies referred to a regional
      center for a level II sonographic examination after 20 weeks' gestation were
      characterized by absent or reversed diastolic flow in the umbilical artery. Ten
      fetuses had congenital malformations or were aneuploid. Ten were growth-retarded
      in association with other problems: maternal hypertension, preeclampsia, cyanotic
      heart disease, elevated maternal serum alpha-fetoprotein levels, or twin
      gestation. In two cases, no etiology could be identified. Knowledge of the fetal
      karyotype, fetal anatomy, gestational age, maternal disease, and fetal status as
      determined by other tests of fetal well-being was required to optimize outcome in
      each case. In view of the heterogeneous etiologies of absent or reversed
      diastolic flow, management of such cases must be individualized.

PMID- 1992403
TI  - Fetal internal carotid artery pulsed Doppler flow velocity waveforms and maternal
      plasma glucose levels.
AB  - Eighteen women at 32-36 weeks' gestation were studied by pulsed Doppler (duplex)
      for recording blood flow velocity waveforms from the umbilical artery and fetal
      intracranial internal carotid artery. The pulsatility index was calculated for
      each artery separately. Each subject was investigated when fasting and 1 hour
      after a 100-g glucose load. Increases in maternal plasma glucose concentration of
      30 mg/dL or more were followed by elevation of the mean pulsatility index in the
      umbilical artery from 0.9 +/- 0.22 to 1.08 +/- 0.18 (P less than .01) and in the
      internal carotid artery from 1.17 +/- 0.19 to 1.8 +/- 0.47 (P less than .001).
      The findings suggest a compensatory increase in cerebrovascular resistance during
      increases in glucose levels.

PMID- 1992404
TI  - Fetal responses to maximal swimming and cycling exercise during pregnancy.
AB  - Fetal responses to maximal maternal exercise were studied during cycle ergometry
      and tethered swimming in 13 untrained subjects at 25 and 35 weeks' gestation. The
      fetal heart rate (FHR) and uterine and umbilical artery waveforms were measured
      before exercise, immediately after exercise, and at 5-minute intervals during 20
      minutes of recovery. The mean maternal maximal heart rate was 179 +/- 12 beats
      per minute and did not differ between swimming and cycling exercise trials. Six
      episodes of transient bradycardia occurred after a total of 45 maximal exercise
      trials. The mean FHR decreased slightly immediately after exercise, then
      increased approximately ten beats above baseline levels at 10-20 minutes after
      exercise (P less than .02). The changes from baseline in FHR were greater after
      cycling than after swimming. Changes observed in the systolic-diastolic ratio
      (S/D) of the umbilical artery could be accounted for by the FHR variations. The
      S/D of the uterine artery was significantly higher after cycling than after
      swimming (P = .05). We conclude that maximal maternal exercise during pregnancy
      causes transient fetal bradycardia in approximately 15% of cases, in cycling more
      often than in swimming.

PMID- 1992405
TI  - Birth weight standards for triplets under modern obstetric care in the United
      States, 1984-1989.
AB  - Birth data were reviewed on 3321 live-born infants from 1138 triplet pregnancies
      delivered in the United States between 1984-1989. The three major etiologies for
      the multiple gestations were fertility drugs (50%), spontaneous (38%), and in
      vitro methods (9%). The average length of gestation was 33.8 weeks and the mean
      birth weight was 1911 g. Neonatal birth weight curves for triplet infants born
      alive in the third trimester were plotted. From 26-35 weeks, the average triplet
      newborn has a weight corresponding to approximately the 30th percentile level
      compared with singletons. After 35 weeks, triplet birth weights fall
      progressively behind those of singletons, reaching the tenth percentile at 38
      weeks. Multiple epidemiologic factors were analyzed to determine their effect
      upon neonatal birth weight and length of gestation. Factors predicting higher
      than average birth weight included male sex, increasing maternal age, increasing
      maternal height and weight, maternal weight gain, and maternal parity. The length
      of gestation was found to correlate with maternal age, weight gain, and parity.
      No significant association between fertility method and gestational age or weight
      could be identified. This large data base provides the first comprehensive
      percentile birth weight rankings for modernly managed triplet gestations in the
      United States population. A regression equation is presented which accurately
      predicts mean triplet birth weight in the third trimester and which suggests that
      a nearly linear weight gain of approximately 150 g per week per fetus should be
      expected in this period.

PMID- 1992406
TI  - A cytogenetic study of spontaneous abortions with direct analysis of chorionic
      villi.
AB  - The karyotypes of 144 spontaneous abortuses were determined using direct
      chromosome preparations from chorionic villi. The frequency of chromosome
      abnormality was 69.4%, which is considerably higher than figures cited in most
      previous cytogenetic surveys using the conventional method of cell culturing.
      Autosomal trisomy was the predominant abnormality (64%), followed by polyploidy
      (9%), monosomy X (7%), structural rearrangements (6%), mosaicism (6%), double
      trisomy (4%), and double chromosome anomaly (3%). Direct preparations have
      advantages in that results can be obtained rapidly, the success rate of
      karyotyping is satisfactory, and maternal-cell contamination is minimal.

PMID- 1992407
TI  - Salpingoscopy: light microscopic and electron microscopic correlations.
AB  - In order to examine the ability of salpingoscopy to diagnose intratubal
      pathology, 32 fallopian tubes were evaluated salpingoscopically and
      histologically. Both flexible and rigid salpingoscopes were used, and
      observations were documented by intratubal photography. Salpingoscopic criteria
      were established and each criterion assigned a numerical value. Each tube was
      evaluated for patency, mucosal fold architecture, erythema, adhesions, and
      dilatation. Based on these criteria, tubes were graded as normal or as abnormal
      with mild, moderate, or severe changes. Histologically, each tube was evaluated
      for patency, epithelial changes, vascularity, dilatation, adhesions, and active
      inflammation. Six tubes with significant histologic findings and two
      histologically normal fallopian tubes were also examined by transmission electron
      microscopy. In five discordant cases, histology revealed epithelial and stromal
      changes not detected by salpingoscopy. Fallopian tubes with severe disease were
      diagnosed by both methods. Transmission electron microscopy of histologically
      abnormal tubes showed flattening of the epithelium with markedly reduced ciliary
      distribution, degenerating secretory epithelial cells with large intracellular
      vacuoles, and swollen nuclei containing sparse chromatin. Our results indicate
      that salpingoscopic observations are consistent with histologic findings when
      endotubal disease is severe. However, moderate pathologic changes as documented
      by light microscopy and transmission electron microscopy were frequently not
      diagnosed salpingoscopically, even with magnification.

PMID- 1992408
TI  - Serial endovaginal sonography of ectopic pregnancies treated with methotrexate.
AB  - Methotrexate therapy is a newly established treatment modality for ectopic
      pregnancy. We performed this study to determine the time frame for resolution of
      the sonographically identifiable mass during such therapy and to determine the
      role of sonography in the management of these patients. Eighteen patients treated
      with methotrexate for laparoscopically proven ectopic pregnancy consented to long
      term follow-up with endovaginal sonography. These 18 patients constitute the
      study group. The time required for sonographic resolution of the mass was
      variable, although poor patient compliance with sonographic follow-up affected
      the conclusions regarding resolution time. One hundred eight days was the longest
      period accurately known for resolution of a mass. In seven patients, the mass
      persisted after a negative hCG titer. Enlargement of the adnexal mass during
      therapy did not necessarily predict treatment failure, as only two of ten such
      patients required surgery for rupture. Serial sonography did not alter the
      management of most patients and appears not to be warranted on a routine basis.
      Follow-up sonography was most useful when complications were suspected. All
      patients considered for methotrexate therapy should first have an endovaginal
      sonogram, as cardiac activity remains a relative contraindication to this
      treatment. We have determined that the mass of an ectopic pregnancy may remain
      after the hCG is negative. Therefore, a persistent mass should not be interpreted
      as treatment failure.

PMID- 1992409
TI  - The effect of doxycycline on serum levels of ethinyl estradiol, norethindrone,
      and endogenous progesterone.
AB  - Doxycycline and other antibiotics have been implicated in oral contraceptive (OC)
      failure, but information is sparse and studies of a doxycycline-OC interaction
      are nonexistent. Because an interaction between doxycycline and OCs, especially
      those containing low-dose estrogen, could result in an unplanned and unwanted
      pregnancy, a controlled clinical trial of the effects of doxycycline on OC
      hormone concentrations was performed. Twenty-four women aged 18-35 years were
      recruited as volunteers from among the patients seen in a University-based family
      planning clinic. While they were on a steady dose of the OC Ortho-Novum 1/35,
      serum concentrations of ethinyl estradiol, norethindrone, and endogenous
      progesterone were measured on days 18, 19, and 20 of the menstrual cycle (control
      phase). These measurements were repeated on days 18, 19, and 20 of the following
      menstrual cycle while the patient was taking doxycycline, 100 mg twice daily
      (treatment phase). No statistically significant differences in serum levels of
      ethinyl estradiol, norethindrone, or endogenous progesterone were seen between
      the control and treatment phases. However, there was large inter-patient and
      intra-patient variability in ethinyl estradiol and norethindrone levels. No
      elevations of endogenous progesterone occurred to suggest ovulation during
      antibiotic administration in either phase. It is not known what effects longer or
      earlier administration of doxycycline during the OC cycle would have on serum
      hormone concentrations or ovulation. Pregnancies attributed to failure of OCs
      because of tetracycline use could in fact be due to other causes or could
      represent a true interaction that only manifests itself in a small proportion of
      women at risk.

PMID- 1992410
TI  - Repetitive conservative surgery for recurrence of endometriosis.
AB  - We evaluated the recovery of fertility and the relief of pain symptoms in a long
      term follow-up of 42 women undergoing repetitive conservative surgery for
      recurrent endometriosis. The mean age of the patients was 31.1 +/- 4.3 years. At
      the time of their second operation the disease was stage IV in 14 women, stage
      III in 25, and stage I in three. After reoperation, the patients were followed
      for a mean period of 41.8 +/- 30.3 months. Pain symptoms returned in eight women,
      dysmenorrhea and deep dyspareunia in eight, and pelvic pain in seven. Eight of
      the 28 women (28.6%) who attempted to conceive achieved a total of 13
      pregnancies. The corrected pregnancy rate was 35%, and the cumulative rate at 27
      months was 30.7%. A third operation was necessary in six women after a mean
      period of 35 months. Conservative surgery is an effective therapeutic option for
      infertile patients with recurrent endometriosis.

PMID- 1992411
TI  - Measures of sexual behavior and the risk of pelvic inflammatory disease.
AB  - A women's sexual behavior affects her risk of acquiring pelvic inflammatory
      disease, but the risks have not been well characterized. To study the association
      between pelvic inflammatory disease and sexual behavior, we analyzed data from a
      multicenter, case-control study involving 712 women hospitalized with an initial
      episode of pelvic inflammatory disease and 2719 hospitalized control women
      without a history of pelvic inflammatory disease. Study participants provided
      information on their frequency of intercourse, number of recent sexual partners,
      and previous history of gonorrhea. Logistic regression methods were used to
      adjust for confounding factors. Women who reported having four or more sexual
      partners were over three times more likely to be hospitalized for pelvic
      inflammatory disease (relative risk 3.4; 95% confidence interval 2.2-5.3) than
      were women who reported only one recent sexual partner. To a lesser extent,
      frequent sexual intercourse and history of gonorrhea also increased a woman's
      risk of pelvic inflammatory disease. Frequent intercourse was a strong risk
      factor for pelvic inflammatory disease among a subgroup of women who were at low
      risk for acquiring a sexually transmitted disease: Married women with one recent
      sexual partner with intercourse six or more times per week had a risk of pelvic
      inflammatory disease of 3.2 (1.4-7.2) compared with similar women having
      intercourse less than once per week. Frequent intercourse, which does not by
      itself increase the risk of acquiring a sexually transmitted disease, may
      increase a woman's risk of pelvic inflammatory disease.

PMID- 1992412
TI  - Amoxicillin treatment of bacterial vaginosis during pregnancy.
AB  - The purpose of this investigation was to evaluate the efficacy of amoxicillin for
      treatment of bacterial vaginosis during pregnancy. The diagnosis of bacterial
      vaginosis was established by clinical examination and microscopic examination of
      a Gram stain and saline preparation of vaginal secretions. In a double-blind,
      randomized manner, 108 patients at 15-25 weeks' gestation were assigned to
      treatment with oral amoxicillin, 500 mg three times daily for 14 days, or
      placebo. Patients were evaluated 2 weeks after treatment, at 34-36 weeks'
      gestation, and at delivery. There were no significant differences between the two
      groups with respect to any clinical or microbiologic measure of treatment
      outcome. There were also no significant differences in the frequency of obstetric
      complications. We conclude that amoxicillin is not effective therapy for
      bacterial vaginosis in pregnant women.

PMID- 1992413
TI  - Enlarged cisterna magna and the Dandy-Walker malformation: factors associated
      with chromosome abnormalities.
AB  - Thirty-three fetuses with an enlarged cisterna magna (10 mm or more) were
      evaluated to determine factors that might be associated with an underlying
      chromosome abnormality. Eighteen fetuses (55%) proved to have a chromosome
      abnormality, including trisomy 18 or trisomy 18 variant (12), trisomy 13 (three),
      Turner syndrome (one), or other rearrangements (two). Among various risk factors
      analyzed, the absence of ventricular dilatation correlated most strongly with a
      chromosome abnormality. Chromosome abnormalities were found in 17 of 22 fetuses
      (77%) lacking ventricular dilatation, compared with only one of 11 fetuses (9%)
      with ventricular dilatation (P less than .001). Other factors statistically
      associated (P less than .01) with an underlying chromosome abnormality included
      mild enlargement of the cisterna magna (10-14 mm), concurrent anomalies detected
      sonographically, and fetal growth retardation. However, stepwise logistic
      regression showed that only the absence of ventricular dilatation and the
      presence of concurrent anomalies were significant when multiple factors were
      evaluated. These observations support the utility of evaluating the cisterna
      magna as part of a routine anatomical survey.

PMID- 1992414
TI  - First- and second-trimester diagnosis of fetal ocular defects and associated
      anomalies: report of eight cases.
AB  - Ocular cataract, hypertelorism, hypotelorism, anophthalmos, and microphthalmos
      are rare malformations commonly associated with other fetal anomalies.
      Previously, ocular malformations were detected only after mid-gestation.
      Transvaginal sonography allows the detection of many structural fetal anomalies.
      We describe the case reports of eight ocular anomalies among 1600 fetal
      screenings by transvaginal sonography at 12-18 weeks' gestation. Severe cataract
      was correctly diagnosed by transvaginal sonography. However, transvaginal
      sonography failed to detect moderate cataract in a case of repeat cataract in a
      subsequent gestation. Anophthalmia may sometimes be secondary to a degenerative
      process in middle and late pregnancy. In five of the eight described cases, the
      eye malformations were associated with defects of the central nervous system.

PMID- 1992415
TI  - Clue cells in predicting infections after abdominal hysterectomy.
AB  - Seventy women scheduled for abdominal hysterectomy were examined for the presence
      of clue cells in the vaginal discharge in an attempt to identify a possible risk
      group for development of postoperative infection. Seven of 20 women (35%) with
      clue cells developed vaginal cuff infections or wound infections, compared with
      four of 50 women (8%) without clue cells (P less than .01). Women with bacterial
      vaginosis, diagnosed by air-dried vaginal smears, are therefore at risk for
      postoperative infection.

PMID- 1992416
TI  - Simple standing incremental cystometry as a screening method for detrusor
      instability.
AB  - One hundred consecutive neurologically normal women complaining of urinary
      incontinence underwent standing incremental retrograde medium-fill water
      cystometrograms on two different days followed by sitting and standing continuous
      retrograde medium-fill water urethrocystometry on a third visit between November
      1987 and February 1989. Studies were done to assess the reproducibility,
      sensitivity, specificity, and predictive values of a simple cystometer. Standing
      incremental, retrograde cystometry was found to be relatively inexpensive,
      simple, reproducible, and sensitive. The two cystometrograms yielded similar
      results in 84% of the patients. The sensitivities were found to be 84.3 and 90.2%
      for the first and second cystometrograms, respectively. Using both
      cystometrograms together, we were able to detect detrusor instability with a
      sensitivity of 92.3% and to predict its absence with a negative predictive value
      of 86.7%. Detrusor instability was found in 64% of these patients. Based on these
      results, it was concluded that when multichannel urodynamics are not available in
      a high-prevalence population, standing retrograde incremental water cystometry
      done on two occasions may offer the physician an accurate alternative for the
      diagnosis of detrusor instability.

PMID- 1992417
TI  - Endometrial carcinoma: the relevance of cervical cytology.
AB  - In patients with endometrial carcinoma, preoperative identification of poor
      prognostic factors is helpful in planning therapy. Extended surgical staging,
      including pelvic and periaortic node dissection, is indicated in patients with
      deep myometrial invasion or high-grade tumor, or when other risk factors for
      extrauterine spread are present. In this study, cervical cytology was reviewed in
      86 patients with endometrial carcinoma, all of whom underwent surgical staging,
      to correlate the cytologic results with surgical and pathologic findings.
      Cervical cytology was normal in 20 patients (23%), whereas suspicious or
      malignant endometrial cells were present in 23 and 43 cases (27 and 50%),
      respectively. Suspicious or malignant cervical cytology was associated with
      deeper myometrial invasion (P = .011), higher postoperative tumor grade (P =
      .006), positive peritoneal washings (P = .012), and more advanced stage by
      International Federation of Gynecology and Obstetrics criteria (P = .024). When
      compared with patients with normal cervical cytology, those who had malignant
      endometrial cells had over twice the risk of deep myometrial invasion (67 versus
      30%), twice the risk of grade 2 or 3 tumor (60 versus 30%), and three times the
      risk of positive peritoneal washings (33 versus 10%). Seventy-four percent of
      patients with malignant cervical cytology were stage IC or more. In contrast, 70%
      of patients with normal cervical cytology were stage IA or IB. Patients with
      endometrial carcinoma who have malignant endometrial cells detected by cervical
      cytology are at increased risk of having a deeply invasive, high-grade, advanced
      stage tumor, and therefore are more likely to require extended surgical staging.

PMID- 1992418
TI  - Retirement patterns of obstetricians and gynecologists.
AB  - A sample survey of 769 ACOG Fellows who were age 60 or older in 1990 was
      undertaken to determine current patterns of retirement. Among 415 respondents,
      only 23% reported remaining in full-time practice of both obstetrics and
      gynecology, with an additional 16% in full-time practice of gynecology only. Full
      time practice was reduced to part-time for 24% at the mean age of 63. Thirty
      eight percent were fully retired at the mean age of 67.

PMID- 1992419
TI  - Development and initial experience with a manually controlled spring wire device
      ("Cordostat") to aid in difficult funipuncture.
AB  - Funipuncture has evolved as a useful tool in prenatal diagnosis and treatment.
      The ease with which it can be performed depends on placental implantation site,
      amniotic fluid volume, fetal presentation and activity, gestational age, and
      operator experience. Under select circumstances, such as hydramnios,
      oligohydramnios/anhydramnios, a back-up fetus/posterior placenta, or gestation of
      fewer than 20 weeks, funipuncture can be difficult or impossible. We have
      developed a new instrument, the "Cordostat," which can help the operator perform
      difficult funipuncture by providing stabilization and allowing intrauterine
      manipulation of the umbilical cord. The instrument consists of a deflecting wire
      guide threaded through a 19.5-guage trochar needle, which can be manually
      controlled to coil around and stabilize a free loop of cord. Conventional
      funipuncture can then be performed through a second uterine puncture. We describe
      use of this instrument in 12 patients undergoing second-trimester induced
      abortion.

PMID- 1992420
TI  - An improved spiral electrode applicator system for fetal heart rate monitoring.
AB  - A new fetal scalp electrode applicator system uses a guide tube with increased
      curvature and a plunger mechanism to advance, rotate, and release the spiral
      electrode. Results of a preliminary survey among house staff who used the system
      in 51 patients indicated a favorable impression, with 96.1% of the applications
      rated as "much better," "better," or "same" as compared with the conventional
      system. The rate for a subset of 26 patients with limited cervical dilatation (1
      3 cm) or high station of the presenting part (-1 to -3) was similarly good
      (92.3%). The characteristics found most favorable were the increased curvature
      for facilitating applications to high presenting parts, the plunger mechanism for
      applying the electrode, and better control of the guide tube.

PMID- 1992421
TI  - Doppler velocimetry of intraplacental fetal arteries.
AB  - Doppler velocimetry of the umbilical and intraplacental fetal arteries was
      studied by color flow mapping in 39 normal pregnancies. The systolic-diastolic
      ratio (S/D) and pulsatility index of the intraplacental fetal artery downstream
      to the umbilical artery decreased significantly with advancing gestational age,
      and its S/Ds were persistently lower than those of the umbilical artery. The
      difference in the S/D between the umbilical artery and its intraplacental
      downstream branches decreased with advancing gestational age and approached zero
      as the pregnancy progressed to term. We conclude that intraplacental fetal
      arteries, possibly fetal arteries in main stem villi, can be imaged by color flow
      mapping and that there is a significant "resistance gradient" between the
      intraplacental fetal artery and the umbilical artery. Intraplacental fetal artery
      velocimetry using color flow mapping may give further insights into the umbilical
      placental circulation.

PMID- 1992422
TI  - Full-thickness skin graft vaginoplasty for treatment of the stenotic or
      foreshortened vagina.
AB  - Vaginal stenosis or foreshortening following surgery or radiation therapy can
      lead to dyspareunia. This report concerns the successful use of full-thickness
      skin grafts taken from the flank overlying the iliac crest to treat vaginal
      stenosis or foreshortening. The operation consists of incising the involved area
      and creating a space which will become the recipient site. An elliptical piece of
      full-thickness skin harvested from the area overlying the iliac crest is cleared
      of underlying fat, trimmed to fit the recipient site, and sutured in place.
      Vaginal packing is used to keep the graft against the recipient bed. Ten patients
      have been treated successfully with this technique, without significant
      complications or sequelae. Follow-up from 6 weeks to 42 months showed excellent
      postsurgical vaginal capacity in all patients. Similarly, excellent functional
      results were achieved in eight patients, with distinct improvement in the
      remaining two. This procedure is a useful addition to the gynecologic surgeon's
      armamentarium.

PMID- 1992423
TI  - Septic shock complicating drainage of a Bartholin gland abscess.

PMID- 1992424
TI  - Window operation: an alternative treatment method for Bartholin gland cysts and
      abscesses.

PMID- 1992425
TI  - The occurrence of simultaneous fetal heart rate accelerations in twins during
      nonstress testing.

PMID- 1992426
TI  - Limb salvage in the treatment of musculoskeletal tumors.

PMID- 1992427
TI  - Introduction to limb-salvage surgery for sarcomas.
AB  - This article provides a history of limb-salvage surgery and definitions of terms
      used to describe aspects of the procedure. Staging is also discussed.

PMID- 1992428
TI  - Mobile knee reconstructions after resection of malignant tumors of the distal
      femur.
AB  - Limb-salvage surgery involving mobile knee reconstructions for malignant tumors
      about the distal femur is a desirable and achievable goal. With limb salvage, the
      survival rate does not decrease significantly, and the resulting function is
      superior to when an amputation plus a prosthesis are used. Immediate and delayed
      morbidity is greater after limb-salvage surgery than after amputation. However,
      with thorough preoperative planning, use of neoadjuvant chemotherapy as
      indicated, and an experienced team of surgeons, limb-salvage surgery can provide
      a mobile knee with excellent function in the vast majority of cases for patients
      with malignant tumors of the distal femur.

PMID- 1992429
TI  - Limb salvage in pediatric surgery. The use of the expandable prosthesis.
AB  - Limb sparing in growing children has proved to be very effective from an
      oncologic perspective, with good, long-term acceptance by the patients. As in the
      adult, when performed by experienced surgeons, limb sparing neither compromises
      the survival rate nor significantly increases the local recurrence rate, compared
      with cross-bone amputation. Discussions include patient evaluation, surgical
      options, materials and methods, and results.

PMID- 1992430
TI  - Resection and reconstruction for bone tumors in the proximal tibia.
AB  - The proximal tibia is a common site for both benign and malignant tumors. This
      article reviews pertinent anatomy, clinical presentation, and staging methods for
      tumors of this area. Discussion is given to various methods of resection and
      reconstruction with useful guidelines for procedure selection. The use of
      allografts for reconstruction is discussed in depth.

PMID- 1992432
TI  - Resection and reconstruction for soft-tissue sarcomas of the extremity.
AB  - Soft-tissue sarcomas are uncommon malignant tumors, and when a diagnosis is made
      early, the patient has up to an 80% chance of surviving. In treating soft-tissue
      sarcomas, the goal of the surgeon is the prolongation of patient survival, the
      total eradication of local disease, and the minimization of functional deficits.
      In addition to treatment, this article discusses evaluation, histology, and
      staging.

PMID- 1992431
TI  - Endoprosthetic reconstruction after bone tumor resections of the proximal tibia.
AB  - The advent of successful adjuvant chemotherapy and radiation therapy protocols
      for primary malignant tumors and the development of custom-designed metallic
      endoprostheses has now made possible a successful limb salvage procedure for
      malignancies of the proximal tibia. Use of the transposed medial gastrocnemius
      flap, as proposed by Dr. Jean Duboussett of Paris, has been critical to the soft
      tissue reconstruction that routinely permits an excellent active and passive
      range of motion for these patients. This article describes the operative
      techniques and technical considerations necessary for a successful proximal
      tibial endoprosthesis reconstruction.

PMID- 1992433
TI  - Allograft reconstructions of the shoulder after bone tumor resections.
AB  - Large skeletal defects resulting from tumor resections about the shoulder create
      reconstructive challenges for the orthopedic surgeon. Bone allografts offer
      several advantages compared with other reconstructive techniques, and functional
      outcomes are generally satisfactory. They may be used either as osteoarticular
      grafts, intercalated segments to create an arthrodesis, or in combination with
      standard proximal humerus metallic implants. Patient expectations and specific
      oncologic factors must be considered when selecting the optimal method of
      reconstruction.

PMID- 1992434
TI  - Resections and reconstructions for tumors of the distal radius.
AB  - The primary objective in surgical management of the patient with a distal radius
      tumor is control of the disease. Accurate staging and diagnostic methods applied
      preoperatively will predict not only the amount of resection necessary to obtain
      adequate tumor margins, but also the amount of remaining bone and soft tissues to
      assist reconstruction. With this information, a method of reconstruction can be
      chosen that provides the patient optimal long-term function and stability with
      predictable results and the fewest potential complications.

PMID- 1992436
TI  - Tumors of the shoulder girdle. Technique of resection and description of a
      surgical classification.
AB  - Limb-sparing surgery is safe and reliable for most bone and soft-tissue tumors of
      the shoulder girdle. Eighty to ninety percent of patients with high-grade
      sarcomas of the shoulder can be safely treated by the various surgical techniques
      described. Attention must be paid to appropriate patient selection, preoperative
      staging, and planning. In addition, careful skeletal and muscular reconstruction
      of the surgical defect is necessary for a successful outcome. A new, universal,
      classification schemata (types I-VI) of shoulder girdle resections has been
      developed. This classification system is based on the bones resected, the status
      of the abductor mechanism, and the relationship to the glenohumeral joint. This
      system permits easy description and comparison of the various limb-sparing
      procedures performed.

PMID- 1992435
TI  - Pelvic resections: the Rizzoli Institute experience.
AB  - Materials, methods, and techniques of pelvic resections are discussed. Results,
      including the complications of nerve damage, infection, and vascular, visceral,
      and reconstructive complications are tabulated.

PMID- 1992437
TI  - Reconstructions after resections of tumors involving the proximal femur.
AB  - Advances in prosthesis design, the use of allografts, and a systematic approach
      to the staging and surgical treatment of musculoskeletal tumors have made limb
      salvage possible in the proximal femoral region. With the use of effective
      adjuvant therapy, limb salvage is now an option for the majority of patients
      presenting with locally invasive neoplasms in this area. The increase in
      functional outcome is sufficient to warrant serious consideration of limb salvage
      over the corresponding amputation. Preoperative planning is discussed along with
      surgical techniques.

PMID- 1992438
TI  - Two c-myb proteins differing by their aminotermini exhibit different
      transcriptional transactivation activities (yeast/reporter-effector system).
AB  - We assayed in the yeast S. cerevisiae the transcriptional transactivation
      activity of the c-myb products encoded by a normal thymus cDNA and of an
      aminoterminally truncated version of it (minus 58 amino acids) corresponding to
      the cDNAs isolated from lymphoma and leukemia cells from different origins. Both
      proto-oncogene products were expressed under the control of the galactose
      inducible GAL10 promoter. The reporter system used to monitor the transactivation
      potential of the myb products consisted of a CYCl-lacZ gene fusion in which the
      UASCYC signals were replaced by one or multiple copies of the myb recognition
      element (mRE). As shown by Northern blot analyses and by primer extension
      experiments both c-myb products increase the level of beta-galactosidase
      transcription. Interestingly, the c-myb product corresponding to lymphoma cDNAs
      stimulates transcription four to five times more efficiently than does the normal
      thymic c-myb product.

PMID- 1992439
TI  - Cell type-specific tumor induction in neural transplants by retrovirus-mediated
      oncogene transfer.
AB  - Using a neural transplantation model which mimics structural and functional
      properties of the normal rat brain to a high extent, we have taken a novel
      approach to study the transforming potential of activated oncogenes in the
      developing brain. Single cell suspensions prepared from fetal rat brains were
      infected with replication-defective retroviral vectors encoding oncogenes and
      stereotaxically injected into the caudoputamen of adult F344 rats. Rats carrying
      transplants expressing the polyoma middle T antigen developed endothelial
      hemangiomas in the graft which in 70% of the recipient animals led to fatal
      cerebral hemorrhage within 13-50 days after transplantation. Expression of the v
      src gene caused astrocytic and mesenchymal tumors with a 70% incidence after
      latency periods of 2-6 months, but no endothelial lesions. It was found by in
      situ hybridization that these oncogenes are expressed in all cell types present
      in the graft. This indicates that cell-type specific transformation is due to
      differential susceptibility of the respective target cell to the oncogenes,
      rather than selective integration or expression of the retroviral construct. The
      highly efficient gene transfer by retroviral vectors into fetal brain transplants
      provides a challenging experimental strategy to study differentiation and
      oncogenesis in the CNS.

PMID- 1992440
TI  - Aggressive subtypes of human colorectal tumors frequently exhibit amplification
      of the c-myc gene.
AB  - Expression of the c-myc gene is often elevated in human colorectal tumors, but
      reported amplification of the locus is rare. Here we demonstrate that modest
      amplification of c-myc is frequently found in aggressive subtypes of colorectal
      cancer. Careful quantitation of c-myc copy number has shown amplification in
      53.8% (7/13) mucinous tumors, 42.3% (3/7) poorly differentiated tumors and a
      single poorly differentiated APUD tumor. This contrasts with amplification in
      6.9% (2/29) moderately to well differentiated tumors, a value which is in
      agreement with that in previously published reports. Such changes in gene copy
      number may represent an important aspect of the genomic alterations which
      accumulate during the development of colorectal tumors.

PMID- 1992442
TI  - Molecular cloning of a rearranged HRAS1 oncogene in chromosome mediated gene
      transfer associated with elevated tumorigenicity.
AB  - We describe the molecular cloning of the rearranged HRAS1 oncogene found in
      association with the increased tumorigenic potential of the chromosome mediated
      gene transfectant E65.5. The rearrangement occurs immediately 3' to the c-Ha-ras
      coding region, removing the variable numbered tandem repeat (VNTR) but not
      altering the HRAS1 transcription unit. The novel 3' DNA sequence contains a short
      open reading frame but shows no homology to any previously cloned elements.
      Sequence analysis identifies a number of short DNA motifs consistent with the
      activity of an aberrant recombinogenic mechanism.

PMID- 1992441
TI  - Molecular structure of double reciprocal translocations: significance in B-cell
      lymphomagenesis.
AB  - The molecular structure of reciprocal translocations associated with low grade
      and high grade non-Hodgkin's lymphomas occurring together was analysed in two
      tumors. Sequential biopsies documented histological transformation of a large
      cell lymphoma to an immunoblastic lymphoma bearing t(14;18)(q32;q21) and
      t(8;22)(q24;q11). A second tumor, a small non-cleaved cell lymphoma, demonstrated
      a t(8;14)(q24;q11) as well as t(18;22)(q21;q11). DNA analysis from these tumors
      showed rearrangements at the Ig heavy chain, kappa and lambda light chains, BCL2
      and c-MYC loci. Utilizing multiple enzyme digests and different probes spanning
      the BCL2, c-MYC and Ig genes, mapping of DNA break-points was performed. In both
      these tumors primary translocation events dysregulating the BCL2 or c-MYC were
      identified to have occurred in a pre-B-cell. Based on these results and those
      published previously, a sequence of B-cell development during which somatic
      recombination errors lead to the genesis of specific translocations is proposed.
      From these studies it is inferred that secondary dysregulation of a c-MYC in a
      lymphoma tumor carrying dysregulated BCL2 gene leads to rapid progression to high
      grade disease.

PMID- 1992443
TI  - Cell cycle dependent association of c-myc protein with the nuclear matrix.
AB  - We demonstrate the presence of a c-myc protein with an apparent molecular weight
      of 67 kd in the lower eukaryote Physarum polycephalum with polyclonal and
      monoclonal anti-c-myc-antibodies. It is shown that the amount of myc protein
      present in the nucleus does not fluctuate during the naturally synchronous cell
      cycle of Physarum. The myc protein remains firmly associated with the nuclear
      matrix after a variety of matrix preparation procedures. Although the level of c
      myc protein is invariant during the cell cycle, the matrix-bound portion of c-myc
      protein is higher during S-phase as compared to G2-period. In immunoelectron
      microscopy the immunosignal was considerably stronger in the nuclear matrix
      compared with unfractionated nuclei, indicating increased accessibility of c-myc
      protein in nuclear scaffold structures. We show that the nuclear localization of
      c-myc protein changes during the cell cycle, being transiently but specifically
      bound to the periphery of the nuclear matrix structure during S-phase.

PMID- 1992444
TI  - Inactivation of the retinoblastoma gene in a human lung carcinoma cell line
      detected by single-strand conformation polymorphism analysis of the polymerase
      chain reaction product of cDNA.
AB  - Combined use of a simple, sensitive method of DNA analysis of nucleotide
      substitutions, namely, single-strand conformation polymorphism analysis of
      polymerase chain reaction products (PCR-SSCP), and the reverse transcriptase
      reaction (RT) is an effective method for mRNA analysis. We used this RT-PCR-SSCP
      method to detect abnormal retinoblastoma (RB) gene transcripts in human tumor
      cell lines. Results showed the presence of two types of RB gene transcripts in a
      giant cell lung carcinoma cell line Lu65: a minor mRNA species with a base
      substitution that created a stop codon in the nucleotide sequence corresponding
      to exon 2 of the gene, and a major species of mRNA without the nucleotide
      sequence corresponding to that of exon 2. PCR-SSCP analysis of the genomic DNA
      also revealed that Lu65 cells contained the mutated RB allele, but not the normal
      allele. These results suggested that in Lu65 cells, both RB alleles were
      inactivated. The transcript without the exon 2 sequence, probably due to
      alternative splicing, was also found in all the other human cells examined, as a
      very minor species.

PMID- 1992445
TI  - Analysis of DNA sequences present in complexes of v-Myc and cellular DNA.
AB  - We have isolated cellular DNA sequences from the myelocytomatosis virus
      transformed quail fibroblastic cell-line (MC29-Q8) by indirect
      immunoprecipitation of v-Myc-DNA complexes and subsequent cloning of the DNA. The
      v-Myc-DNA complexes were obtained from isolated nuclei pretreated with 150 mM
      salt and indirect immunoprecipitation of the p110 Gag-Myc protein with the IgG of
      a Gag-specific monoclonal antibody. A non-specific monoclonal IgG was used as
      control to account for non-specific interactions. The DNA from the precipitates
      was isolated, cloned and characterized. 21 positive and 13 control clones with
      inserts ranging in size from 25 to 330 nucleotides were sequenced and analyzed
      for sequence homologies to known DNA-motives. Some of the sequences over
      represented in the specific DNA fragments corresponded to elements which have
      been previously described to promote DNA amplification. Six of these DNA
      fragments were tested for their ability to promote DNA amplification by insertion
      into a plasmid containing the HSV-1 tk gene with a truncated promoter. These
      constructs were transfected into mouse Ltk- cells which grow under HAT selection
      only upon amplification of the tk-carrying plasmids. Two of the six DNA fragments
      showed the capability to amplify their plasmids in cis and create stable cellular
      clones. Copy numbers of the amplified plasmids in these Ltk+ clones ranged from
      470 to 680 whereby the amplified sequences were integrated as large clusters of
      head-to-tail tandems. The data presented here suggest that the Myc protein may be
      involved in DNA amplification and therefore may play a role in DNA replication.

PMID- 1992446
TI  - Low mitogenic response to EGF and TGF-alpha: a characteristic feature of cultured
      Kaposi's sarcoma derived cells.
AB  - We have investigated the mitogenicity of Epidermal Growth Factor (EGF) and
      Transforming Growth Factor alpha (TGF-alpha) for cultured Kaposi's sarcoma
      derived cells (KS cells). In contrast to control fibroblasts from the same
      patients, KS cells revealed only a weak mitogenic response to these growth
      factors. Neither EGF nor TGF-alpha were able to substitute for Platelet-derived
      growth factor (PDGF) when KS cells were grown in PDGF-depleted Platelet-Poor
      Plasma serum (PPPS)-supplemented medium. The low mitogenicity of EGF and TGF
      alpha for KS cells is not based upon a reduced expression of EGF receptor mRNA
      and protein in KS cells. However, the binding of EGF to KS cells is about 50%
      lower than that to fibroblasts. This reduced binding is not due to an occupation
      of the receptors by TGF-alpha since the expression level of this mitogen in
      different KS cell lines does not correlate with their capacity to bind EGF. In
      contrast, the low EGF binding seems to be an intrinsic feature of the EGF
      receptors of KS cells. In spite of the low mitogenicity of EGF for the tumor
      cells, the expression of c-myc, PDGF-A and Fibroblast growth factor 5 (FGF-5)
      mRNA is equally induced by purified EGF in KS cells and fibroblasts. This shows
      that at least the signal transduction pathways which lead to the expression of
      these genes are functional in KS cells.

PMID- 1992447
TI  - Molecular definition in a somatic cell hybrid of a specific 2:13 translocation
      breakpoint in childhood rhabdomyosarcoma.
AB  - A consistent, balanced, reciprocal chromosomal translocation t(2:13) (q35:q14)
      has been identified in alveolar rhabdomyosarcoma. Somatic cell hybrids have been
      constructed between rhabdomyosarcoma cell lines carrying the (2:13) translocation
      and mouse 3T3 cells. One hybrid cell line was shown to have retained the
      derivative (13:2) chromosome, but segregated the normal chromosome 13 and the
      derivative (2:13) chromosome. Using available DNA probes from human chromosome 13
      we find that the loci for retinoblastoma, esterase D, p7D2, pG24E6.8 and pG14E1.9
      lie distally to the 13q14 breakpoint, whereas those for p7F12, pHU10 and pG2E3.1
      all lie proximally. Thus we have defined a region of 13q14 of approximately 28mB
      which contains the breakpoint associated with this rearrangement.

PMID- 1992448
TI  - Myc protein structure: localization of DNA-binding and protein dimerization
      domains.
AB  - Wildtype and mutant v-Myc proteins were overexpressed in Escherichia coli using
      the T7 RNA polymerase system, and the in vitro DNA-binding activities of
      partially or highly purified proteins were analysed by native DNA-cellulose
      chromatography. For the construction of the expression plasmids, cloned proviral
      DNA from wildtype MC29 or from its spontaneous deletion mutant Q10C was used, the
      latter lacking internal v-myc sequences. Both the wildtype (p59) and the mutant
      (p42) recombinant protein contain at their amino termini 12 amino acids encoded
      by the vector, followed by 11 gag amino acids and 9 amino acids encoded by v-myc
      sequences derived from noncoding c-myc sequences. In addition, p59 contains 416
      amino acids encoded by v-myc sequences derived from the complete chicken c-myc
      coding region, whereas p42 lacks 120 amino acids from the central region of the
      Myc protein including the highly acidic domain. Two additional proteins were
      engineered which contain the first 309 (p53) or the last 107 (p16) amino acids,
      respectively, of the Myc protein sequence in addition to vector-encoded amino
      acids. The p16 protein represents the carboxyl terminus of the Myc protein
      sequence containing both a muscle determination gene (MyoD1) homology region,
      including a basic motif and an amphipathic helix-loop-helix motif, and a leucine
      heptad repeat. All proteins, except p53 which lacks the carboxyl-terminal Myc
      protein sequences, bound to native DNA-cellulose and were eluted with 200-500 mM
      NaCl. Based on the DNA-binding activities of recombinant or spontaneous mutant v
      Myc proteins extracted from bacterial or from transformed avian cells, we
      conclude that the DNA-binding domain of avian Myc proteins is confined within the
      last 86 carboxyl-terminal amino acids. The same region is also shown to be
      necessary and sufficient for Myc protein dimerization. This 86-amino acid region
      essentially encompasses a putative basic DNA contact surface and a tandem array
      of two presumed protein dimerization motifs, helix-loop-helix and leucine repeat.

PMID- 1992450
TI  - Recurrent epistaxis.
AB  - Epistaxis in the pediatric patient is a relatively common, and usually easily
      controlled, event. The practitioner should be aware of the anatomy, potential
      causes, and methods of control available for this condition.

PMID- 1992449
TI  - Clinical disorders of neutropenia.

PMID- 1992451
TI  - Conduct disorders in children and adolescents.

PMID- 1992452
TI  - Specific initiation by RNA polymerase I in a whole-cell extract from yeast.
AB  - A protocol is described for making a soluble whole-cell extract from yeast
      (Saccharomyces cerevisiae) that supports active and specific transcription
      initiation by RNA polymerases I, II, and III. Specific initiation by polymerase I
      decreases in high-density cultures, paralleling the decrease in abundance of the
      endogenous 35S rRNA precursor. This extract should be useful for studying the
      molecular mechanisms that regulate rRNA transcription in yeast.

PMID- 1992453
TI  - Accurate and efficient RNA polymerase II transcription with a soluble nuclear
      fraction derived from Drosophila embryos.
AB  - We describe the preparation and biochemical properties of a soluble nuclear
      fraction derived from Drosophila embryos. This extract, which can be easily
      prepared in 2.5 hr, is capable of accurate and efficient RNA polymerase II
      transcription of a variety of diverse genes from both Drosophila and mammals.
      With the relatively strong promoter of the Drosophila Kruppel gene, it is
      possible to achieve 20% template usage in a single round of transcription, which
      is considerably higher than the template usage of approximately 3% seen with
      standard nuclear extracts. Further, although U small nuclear RNA genes are
      refractory to transcription with HeLa transcription extracts, the soluble nuclear
      fraction transcribes a U1 small nuclear RNA gene from Drosophila. Moreover,
      transcriptional activation by sequence-specific activators can be attained in
      vitro with the soluble nuclear fraction. The overall transcriptional efficiency
      appears limited to 0.45 transcript per template of DNA per 30 min, but the
      mechanism of limitation is not known. The soluble nuclear fraction, which was
      developed to recreate the environment within the nucleus, should be useful when
      high efficiencies of RNA polymerase II transcription are desired.

PMID- 1992454
TI  - Temporal and spatial patterns of transgene expression in aging adult mice provide
      insights about the origins, organization, and differentiation of the intestinal
      epithelium.
AB  - We have used liver fatty acid-binding protein/human growth hormone (L-FABP/hGH)
      fusion genes to explore the temporal and spatial differentiation of intestinal
      epithelial cells in 1- to 12-month-old transgenic mice. The intact, endogenous L
      FABP gene (Fabpl) was not expressed in the colon at any time. Young adult
      transgenic mice containing nucleotides -596 to +21 of the rat L-FABP gene linked
      to the hGH gene (minus its 5' nontranscribed domain) demonstrated inappropriate
      expression of hGH in enterocytes and many enteroendocrine cells of most proximal
      and mid-colonic crypts (glands). Rare patches of hGH-negative crypts were
      present. With increasing age, a wave of "extinction" of L-FABP (-596 to +21)/hGH
      expression occurred, first in the distal colon and then in successively more
      proximal regions, leaving by 10 months of age only rare hGH-positive multicrypt
      patches. At no time during this progressive silencing of transgene expression
      were crypts observed that contained a mixture of hGH-positive and -negative cells
      at a particular cell stratum. Young (5-7 weeks) mice containing a L-FABP (-4000
      to +21)/hGH transgene also demonstrated inappropriate expression of the transgene
      in most proximal colonic crypts. However, the additional 3.3 kilobases of
      upstream sequence resulted in much more rapid extinction of reporter expression,
      leaving by 5 months of age only scattered single crypts with detectable levels of
      hGH. This age-related extinction of L-FABP/hGH expression did not involve
      enterocytes and enteroendocrine cells in the (proximal) small intestine. These
      results indicate that cis-acting elements outside of nucleotides -4000 to +21 are
      necessary to fully modulate suppression of colonic L-FABP expression. They also
      define fundamental changes in colonic epithelial cell populations during adult
      life. Our data suggest that (i) a single stem cell gives rise to all cells that
      populate a given colonic crypt, (ii) stem cells represented in several adjacent
      crypts may be derived from a common progenitor, and (iii) such a progenitor cell
      may repopulate colonic crypts with stem cells during adult life. Since each
      colonic crypt contains the amplified descendants of its stem cell, transgenes may
      be powerful tools for characterizing the spatial and biological features of gut
      stem cells and their progenitors during life.

PMID- 1992455
TI  - Heterochromatic features of an 11-megabase transgene in brain cells.
AB  - Transgenic mice provide a remarkable experimental setting for the study of
      nuclear architecture. The three-dimensional localization and fine structure of a
      foreign DNA within the mouse genome can be conveniently followed by using high
      resolution in situ hybridization. Foreign DNAs designed with specific
      characteristics, such as base bias, sequence motif(s), and size can stably
      integrate into finite positions on host chromosomes. Thus the relative importance
      of each of these characteristics in determining the three-dimensional nuclear
      position and the detailed morphology of the transgene can be evaluated in
      different cell types. The aim of this study was to evaluate a transgene with
      sequence characteristics that might contribute to the de novo formation of
      heterochromatin in interphase nuclei. The structure of a phenotypically silent 11
      megabase transgene, containing tandem repeats of beta-globin-pBR sequences
      integrated into the peritelomeric region of both mouse chromosome 3 homologs, was
      determined in adult brain cells. Neurons that are largely euchromatic were
      especially informative in three-dimensional studies of transgene position. The
      two transgenic loci behaved much like centromeric or paracentromeric A + T-rich
      satellite DNAs of comparable length from a single chromosome; one or both
      transgene domains localized together with centromeric satellite DNA on the
      nucleolus. This is an unusual nuclear position for a telomeric or chromosome arm
      region that does not contain a substantial amount of constitutively
      heterochromatic satellite DNA. G + C richness did not prevent these regions from
      assembling as dense heterochromatic bodies of approximately 1 micron3 in volume.
      Ultrastructurally, transgenic domains were often intimately connected with
      constitutive heterochromatin and were highly condensed. Labeled supercoils,
      formed by a discrete approximately 250-nm-wide fiber, were observed in oblique
      thin sections through the center of the domain. The structural data were
      consistent with negligible transcriptional activity detected for this locus, as
      well as the predicted conformation of constitutive heterochromatin.
      Interestingly, in transgenic but not control mice, a substantial number of large
      neurons, including approximately 30% of cerebellar Purkinje cells, showed
      excessive invaginations of the nuclear membrane.

PMID- 1992456
TI  - Recombinant fusion protein identified by lepromatous sera mimics native
      Mycobacterium leprae in T-cell responses across the leprosy spectrum.
AB  - Pooled polyvalent sera from lepromatous leprosy patients were used to screen a
      lambda gt11 recombinant DNA expression library of Mycobacterium leprae in order
      to identify the relevant antigens recognized by the human immune response. Of the
      300,000 phages screened, 4 clones were identified that coded for fusion proteins
      of the same molecular mass. The fusion protein from clone LSR2 was tested for
      immunoreactivity in assays using peripheral blood cells and sera from 11
      laboratory personnel and 105 patients across the leprosy spectrum. LSR2 protein
      appears to be predominantly a T-cell antigen. It evokes similar
      lymphoproliferative responses as the native bacillus both at the individual level
      and in the leprosy spectrum as a whole. Though only 50% of patient sera with anti
      M. leprae antibodies reacted with the fusion protein, the pattern of reactivity
      in the antibody responses was also similar for the various clinical types. The
      coding regions of clones LSR1 and LSR2 are identical. They show no homology with
      sequences stored in data banks and encode a protein of 89 amino acids with a
      calculated molecular mass of approximately 10 kDa.

PMID- 1992457
TI  - The role of envelope proteins in hepatitis B virus assembly.
AB  - Hepatitis B virus (HBV) particles are generated by budding of preformed
      cytoplasmic nucleocapsids into endoplasmic reticulum (ER) membranes containing
      the three viral envelope proteins (L, M, and S). We have examined the
      contributions of the envelope proteins to virion assembly by using cultured
      hepatoma cells transfected with mutant HBV genomes bearing lesions in the
      envelope coding regions. We show here that HBV nucleocapsids are not released
      from cells without expression of envelope proteins, implying an active role for
      these proteins in viral morphogenesis. S and L but not M proteins are necessary
      for virion production. L protein over-expression inhibits virion release, just as
      it inhibits the release of subviral hepatitis B surface antigen (HBsAg)
      particles. Mutant L proteins that are no longer capable of retaining HBsAg
      particles in the ER still allow virion formation, indicating that this ER
      retention reaction is not required for viral budding. Myristoylation of L protein
      is also dispensable for virion formation. A chimeric protein bearing foreign
      epitopes fused to the S protein can be incorporated into virions when coexpressed
      with the wild-type envelope proteins. Models for the dependence of virion
      formation on both L and S proteins are discussed.

PMID- 1992458
TI  - Cloned Erwinia chrysanthemi out genes enable Escherichia coli to selectively
      secrete a diverse family of heterologous proteins to its milieu.
AB  - The out genes of the enterobacterial plant pathogen Erwinia chrysanthemi are
      responsible for the efficient extracellular secretion of multiple plant cell wall
      degrading enzymes, including four isozymes of pectate lyase, exo-poly-alpha-D
      galacturonosidase, pectin methylesterase, and cellulase. Out- mutants of Er.
      chrysanthemi are unable to export any of these proteins beyond the periplasm and
      are severely reduced in virulence. We have cloned out genes from Er. chrysanthemi
      in the stable, low-copy-number cosmid pCPP19 by complementing several transposon
      induced mutations. The cloned out genes were clustered in a 12-kilobase
      chromosomal DNA region, complemented all existing out mutations in Er.
      chrysanthemi EC16, and enabled Escherichia coli strains to efficiently secrete
      the extracellular pectic enzymes produced from cloned Er. chrysanthemi genes,
      while retaining the periplasmic marker protein beta-lactamase. DNA sequencing of
      a 2.4-kilobase EcoRI fragment within the out cluster revealed four genes arranged
      colinearly and sharing substantial similarity with the Klebsiella pneumoniae
      genes pulH, pulI, pulJ, and pulK, which are necessary for pullulanase secretion.
      However, K. pneumoniae cells harboring the cloned Er. chrysanthemi pelE gene were
      unable to secrete the Erwinia pectate lyase. Furthermore, the Er. chrysanthemi
      Out system was unable to secrete an extracellular pectate lyase encoded by a gene
      from a closely related plant pathogen. Erwinia carotovora ssp. carotovora. The
      results suggest that these enterobacteria secrete polysaccharidases by a
      conserved mechanism whose protein-recognition capacities have diverged.

PMID- 1992459
TI  - Structural analysis of the interaction between the human immunodeficiency virus
      Rev protein and the Rev response element.
AB  - The specific interaction between a defined structural element of the human
      immunodeficiency virus mRNA (RRE, the Rev response element) and the virus-encoded
      protein Rev has been implicated in the regulation of the export of unspliced or
      singly spliced mRNA from the nucleus to the cytoplasm. Rev protein was expressed
      and purified from insect cells using the baculovirus expression system. Chemical
      and RNase probes were used to analyze the structure of the RRE and the regions
      involved in Rev binding. Increased reactivity to single-strand-specific probes of
      nucleotides in two helical domains indicates that Rev binding induces
      conformational changes in the RRE. Binding of Rev to the RRE primarily protects
      helical segments and adjacent nucleotides in domain II. A Rev unit binding site
      is proposed that consists of a six-base-pair helical segment and three adjacent
      nucleotides. The data also suggest that multiple Rev proteins bind to repeated
      structural elements of the RRE.

PMID- 1992460
TI  - Regulation of ferritin and heme oxygenase synthesis in rat fibroblasts by
      different forms of iron.
AB  - Synthesis of the iron-storage protein ferritin is thought to be regulated at the
      translational level by the cytosolic content of chelatable iron. This response to
      iron is regulated by the iron-modulated binding to ferritin mRNAs of a repressor
      protein, the iron regulatory element-binding protein. From measurements made in a
      cell-free system, regulation of the iron regulatory element-binding protein has
      been recently suggested to involve direct interaction with hemin. The following
      observations on the synthesis of ferritin and of heme oxygenase (HO), the heme
      degrading enzyme, in rat fibroblasts or hepatoma cells lead us to conclude that
      chelatable iron is a direct physiological regulator of ferritin synthesis in
      intact cells: (i) the inhibitor of heme degradation, tin mesoporphyrin IX,
      reduces the ability of exogenous hemin to induce ferritin synthesis but enhances
      HO synthesis; (ii) the iron chelator desferal suppresses the ability of hemin to
      induce synthesis of ferritin but not of HO; (iii) the heme synthesis inhibitor
      succinylacetone does not block iron induction of ferritin synthesis; (iv) there
      is no apparent relationship between the ability of various metalloporphyrins to
      inactivate the iron regulatory element-binding protein in cell-free extracts and
      their capacity to induce ferritin synthesis in intact cells; (v) administered
      inorganic iron significantly induces the synthesis of ferritin but not of HO;
      (vi) addition of delta-aminolevulinic acid to stimulate heme synthesis represses
      the ability of inorganic iron to induce ferritin synthesis while activating HO
      synthesis. Taken together, our results demonstrate that (i) release of iron by HO
      plays an essential role in the induction of ferritin synthesis by heme and (ii)
      chelatable iron can regulate ferritin synthesis independently of heme formation.

PMID- 1992461
TI  - Phosphoramidon blocks the pressor activity of porcine big endothelin-1-(1-39) in
      vivo and conversion of big endothelin-1-(1-39) to endothelin-1-(1-21) in vitro.
AB  - In porcine aortic endothelial cells, the 21-amino acid peptide endothelin-1 (ET
      1) is formed from a 39-amino acid intermediate called "big endothelin-1" (big ET
      1) by a putative ET-converting enzyme (ECE) that cleaves the 39-mer at the bond
      between Trp-21 and Val-22. Since big ET-1 has only 1/100-1/150th the contractile
      activity of ET-1, inhibition of ECE should effectively block the biological
      effects of ET-1. Big ET-1 injected intravenously into anesthetized rats produces
      a sustained pressor response that presumably is due to conversion of big ET-1
      into ET-1 by ECE. We determined the type of protease activity responsible for
      this conversion by evaluating the effectiveness of protease inhibitors in
      blocking the pressor response to big ET-1 in ganglion-blocked anesthetized rats.
      The serine protease inhibitor leupeptin, the cysteinyl protease inhibitor E-64,
      and the metalloprotease inhibitors captopril and kelatorphan were all ineffective
      at blocking the pressor response to big ET-1. However, the metalloprotease
      inhibitors phosphoramidon and thiorphan dose-dependently inhibited the pressor
      response to big ET-1, although phosphoramidon was substantially more potent than
      thiorphan. None of the inhibitors blocked the pressor response to ET-1 and none
      had any effect on mean arterial pressure when administered alone. In a rabbit
      lung membrane preparation, ECE activity was identified that was blocked by the
      metalloprotease inhibitors phosphoramidon and 1,10-phenanthroline in a
      concentration-dependent manner. This enzyme converted big ET-1 to a species of ET
      that comigrated on HPLC with ET-1 and produced an ET-like contraction in isolated
      rat aortic rings. Our results suggest that the physiologically relevant ECE is a
      metalloprotease.

PMID- 1992462
TI  - Negative supercoiling of DNA facilitates an interaction between transcription
      factor IID and the fibroin gene promoter.
AB  - Transcription of the fibroin gene can be reconstituted with partially purified
      components from HeLa cells. Transcription factors IIB, IID, and IIE and RNA
      polymerase II are required for accurate initiation of transcription. Linear and
      relaxed closed circular DNA show a similar level of template activity. However,
      transcription of closed circular DNA is stimulated when negative supercoils are
      introduced by the addition of DNA topoisomerase II and supercoiling factor
      purified from the posterior silk gland of Bombyx mori. Dissection of
      transcription into pre- and postinitiation steps by the use of Sarkosyl reveals
      that DNA supercoiling promotes formation of a preinitiation complex. Furthermore,
      order of addition experiments suggest that DNA supercoiling facilitates a
      functional binding of transcription factor IID to the promoter.

PMID- 1992463
TI  - Photoreceptor peripherin is the normal product of the gene responsible for
      retinal degeneration in the rds mouse.
AB  - Retinal degeneration slow (rds) is a retinal disorder of an inbred strain of mice
      in which the outer segment of the photoreceptor cell fails to develop. A
      candidate gene has recently been described for the rds defect [Travis, G. H.,
      Brennan, M. B., Danielson, P. E., Kozak, C. & Sutcliffe, J. G. (1989) Nature
      (London) 338, 70-73]. Neither the identity of the normal gene product nor its
      intracellular localization had been determined. We report here that the amino
      acid sequence of the bovine photoreceptor-cell protein peripherin, which was
      previously localized to the rim region of the photoreceptor disk membrane, is
      92.5% identical to the sequence of the mouse protein encoded by the normal rds
      gene. The differences between the two sequences can be attributed to species
      variation. Monoclonal antibodies were used with Western blot analysis to localize
      the wild-type mouse peripherin/rds protein to isolated mouse rod outer segments
      and to show that it, like bovine peripherin, exists as two subunits linked by one
      or more disulfide bonds. The relative amounts of peripherin/rds protein and
      rhodopsin in retinal extracts of normal and rds mutant mice were also compared.
      Identification of peripherin as the protein encoded by the normal rds gene and
      its localization to membranes of rod outer segments will serve as a basis for
      studies directed toward defining the role of this protein in the morphogenesis
      and maintenance of the outer segment and toward understanding the mechanism by
      which the rds mutation causes retinal degeneration.

PMID- 1992464
TI  - Sequence requirement for peptide recognition by rat brain p21ras protein
      farnesyltransferase.
AB  - We tested 42 tetrapeptides for their ability to bind to the rat brain p21ras
      protein farnesyltransferase as estimated by their ability to compete with p21Ha
      ras in a farnesyltransfer assay. Peptides with the highest affinity had the
      structure Cys-A1-A2-X, where positions A1 and A2 are occupied by aliphatic amino
      acids and position X is occupied by a COOH-terminal methionine, serine, or
      phenylalanine. Charged residues reduced affinity slightly at the A1 position and
      much more drastically at the A2 and X positions. Effective inhibitors included
      tetrapeptides corresponding to the COOH termini of all animal cell proteins known
      to be farnesylated. In contrast, the tetrapeptide Cys-Ala-Ile-Leu (CAIL), which
      corresponds to the COOH termini of several neural guanine nucleotide binding (G)
      protein gamma subunits, did not compete in the farnesyl-transfer assay. Inasmuch
      as several of these proteins are geranylgeranylated, the data suggest that the
      two isoprenes (farnesyl and geranylgeranyl) are transferred by different enzymes.
      A biotinylated heptapeptide corresponding to the COOH terminus of p21Ki-rasB was
      farnesylated, suggesting that at least some of the peptides serve as substrates
      for the transferase. The data are consistent with a model in which a hydrophobic
      pocket in the protein farnesyltransferase recognizes tetrapeptides through
      interactions with the cysteine and the last two amino acids.

PMID- 1992465
TI  - Cord factor (alpha,alpha-trehalose 6,6'-dimycolate) inhibits fusion between
      phospholipid vesicles.
AB  - The persistence of numerous pathogenic bacteria important in disease states, such
      as tuberculosis, in humans and domestic animals has been ascribed to an
      inhibition of fusion between the phagosomal vesicles containing the bacteria and
      lysosomes in the host cells [Elsbach, P. & Weiss, J. (1988) Biochim. Biophys.
      Acta 974, 29-52; Thoen, C. O. (1988) J. Am. Vet. Med. Assoc. 193, 1045-1048]. In
      tuberculosis this effect has been indirectly attributed to the production of cord
      factor (alpha,alpha-trehalose 6,6'-dimycolate). We show here that cord factor is
      extraordinarily effective at inhibiting Ca2(+)-induced fusion between
      phospholipid vesicles and suggest a mechanism by which cord factor confers this
      effect. These findings are likely to be important in our understanding of the
      pathogenesis and treatment of many diseases of bacterial etiology.

PMID- 1992466
TI  - Electron probe microanalysis of calcium release and magnesium uptake by
      endoplasmic reticulum in bee photoreceptors.
AB  - Honey bee photoreceptors contain large sacs of endoplasmic reticulum (ER) that
      can be located unequivocally in freeze-dried cryosections. The elemental
      composition of the ER was determined by electron probe x-ray microanalysis and
      was visualized in high-resolution x-ray maps. In the ER of dark-adapted
      photoreceptors, the Ca concentration was 47.5 +/- 1.1 mmol/kg (dry weight) (mean
      +/- SEM). During a 3-sec nonsaturating light stimulus, approximately 50% of the
      Ca content was released from the ER. Light stimulation also caused a highly
      significant increase in the Mg content of the ER; the ratio of Mg uptake to Ca
      released was approximately 0.7. Our results show unambiguously that the ER is the
      source of Ca2+ release during cell stimulation and suggest that Mg2+ can nearly
      balance the charge movement of Ca2+.

PMID- 1992467
TI  - Signal transduction in bacteria: CheW forms a reversible complex with the protein
      kinase CheA.
AB  - An essential step in the signal transduction pathway of Escherichia coli is the
      control of the protein kinase activity of CheA by the chemotaxis receptor
      proteins. This control requires the participation of the CheW protein. Although
      the biochemical nature of the coupling between the receptors and the kinase is
      unknown, it is likely that CheW interacts with the receptors and with CheA. In
      this communication, we report direct measurement of a physical interaction
      between CheW and CheA. We utilized the equilibrium column chromatography method
      of Hummel and Dreyer to show that CheW and CheA exhibit reversible binding with
      the stoichiometry of two CheW monomers per CheA dimer. CheW was found to exist as
      monomers and CheA was found to exist as dimers by equilibrium analytical
      ultracentrifugation. The dissociation constant for the CheW-CheA interaction (in
      160 mM KCl/5 mM MgCl2, pH 7.4 at 4 degrees C) was determined to be in the
      physiologically relevant range of 17 microM. No evidence for cooperativity in the
      association of CheW with CheA was found.

PMID- 1992468
TI  - Mutated recombinant human heavy-chain ferritins and myelosuppression in vitro and
      in vivo: a link between ferritin ferroxidase activity and biological function.
AB  - Human heavy-chain (H-) ferritin muteins obtained by oligonucleotide site-directed
      mutagenesis, together with wild-type recombinant human H- and light-chain (L-)
      ferritins, were evaluated for in vitro effects on the suppression of human bone
      marrow myeloid progenitor cells and for in vivo effects on marrow and splenic
      myelopoiesis in C3H/HeJ mice. The 10 H-ferritin muteins exhibited alterations of
      various regions of the molecule, including ones exposed on the outer surface, on
      the inner cavity, and on the hydrophilic and hydrophobic channels and of the four
      alpha-helix bundle forming the subunit structure. They were stable and were
      electrophoretically analogous to wild-type H-ferritin. The muteins showed in
      vitro and in vivo myelosuppressive activity analogous to wild type, except for
      mutein 222, which was totally inactive and which lacked ferroxidase activity.
      Recombinant human L-ferritin, devoid of ferroxidase activity, was also inactive
      as a suppressor. The results demonstrate that H-ferritin myelosuppressive and
      ferroxidase activities are linked. One possibility is that ferroxidase activity
      may interfere with the cellular uptake of transferrin iron that is needed for
      cell proliferation, an interpretation consistent with the presently described
      ability of hemin to overcome H-ferritin suppressive effects.

PMID- 1992469
TI  - Cholinergic depletion prevents expansion of topographic maps in somatosensory
      cortex.
AB  - Although the role of acetylcholine in processing stimuli in the cerebral cortex
      is becoming defined, the impact of cholinergic activity on the character of
      cortical maps remains unclear. In the somatosensory cortex, topographic maps
      appear capable of lifelong modifications in response to alterations in the
      periphery. One factor proposed to influence this adaptational ability is the
      presence of acetylcholine in the cortex. The studies presented here, using the 2
      deoxyglucose technique, demonstrate that the unilateral removal of a digit in
      cats, followed by stimulation of an adjacent digit, produces a pattern of
      metabolic activity in the somatosensory cortex that is dramatically expanded when
      compared with the opposite (normal) hemisphere. In contrast, experiments in which
      the somatosensory cortex was depleted of acetylcholine and the animal received a
      similar amputation led not to patterns of expanded metabolic activity, but rather
      to reductions in the evoked metabolic distribution. These studies implicate
      acetylcholine in normal map formation and in the maintenance of the capacity of
      cortical maps to adapt to changes in the periphery.

PMID- 1992470
TI  - Expression of a conserved cell-type-specific protein in nerve terminals coincides
      with synaptogenesis.
AB  - Contact of axons with target territories results in the formation of synapses,
      specific junctional complexes that may represent a final stage of neuronal
      maturation. Synaptosomal-associated protein 25 (SNAP-25) is a component of
      particular nerve terminals recently identified in rodent brain. To evaluate the
      structure and regulation of molecular components of the synapse, we investigated
      the expression of SNAP-25 in the developing chicken nervous system. Analysis of
      SNAP-25 cDNA clones demonstrated that the chicken homologue is identical in amino
      acid sequence to the mouse protein. In chicken retina and neural tube, the onset
      of SNAP-25 mRNA and protein expression was found to correspond to the time of
      synaptogenesis. These results suggest that SNAP-25 plays a role in the physiology
      of mature nerve terminals and that its expression may be regulated by specific
      cell-cell interactions occurring during synapse formation.

PMID- 1992471
TI  - Identification of a T-cell-specific transcriptional enhancer located 3' of C
      gamma 1 in the murine T-cell receptor gamma locus.
AB  - A transcriptional enhancer element has been localized 3 kilobases 3' of the
      murine T-cell receptor C gamma 1 locus using a chloramphenicol acetyltransferase
      reporter gene construct. As a monomer the enhancer functions only in PEER gamma
      delta cells and Jurkat alpha beta cells of the T-cell lines tested. However, a
      tetramer of the enhancer functions in virtually all T-cell lines tested,
      including alpha beta T-cell lines, but not in other cell types. These results
      suggest that elements other than the enhancer are responsible for the failure of
      rearranged C gamma 1 genes to be expressed in alpha beta T cells. The enhancer
      has been localized to a 200-base-pair Rsa I restriction fragment, which contains
      sequence motifs similar to those found in the other T-cell receptor enhancers but
      not in the immunoglobulin enhancers.

PMID- 1992472
TI  - Splice-mediated insertion of an Alu sequence inactivates ornithine delta
      aminotransferase: a role for Alu elements in human mutation.
AB  - In studies of mutations causing deficiency of ornithine delta-aminotransferase
      (EC 2.6.1.13), we found an allele whose mature mRNA has a 142-nucleotide
      insertion at the junction of sequences from exons 3 and 4. The insert derives
      from an Alu element in ornithine delta-aminotransferase intron 3 oriented in the
      direction opposite to transcription (an "antisense Alu"). A guanine----cytosine
      transversion creates a donor splice site in this Alu, activating a cryptic
      acceptor splice site at its 5' end and causing splice-mediated insertion of an
      Alu fragment into the mature ornithine-delta-aminotransferase mRNA. We note that
      the complement of the Alu consensus sequence has at least two cryptic acceptor
      sites and several potential donor sequences and predict that similar mutations
      will be found in other genes.

PMID- 1992473
TI  - Comparison of long and short forms of the prolactin receptor on prolactin-induced
      milk protein gene transcription.
AB  - The biological activities of long and short forms of the prolactin receptor have
      been compared. These two receptors expressed in mammalian cells were shown to
      bind prolactin with equal high affinity. The ability of these different forms to
      transduce the hormonal message was estimated by their capacity to stimulate
      transcription by using the promoter of a milk protein gene fused to the
      chloramphenicol acetyltransferase (CAT) coding sequence. Experiments were
      performed in serum-free conditions to avoid the effect of lactogenic factors
      present in serum. An approximately 17-fold induction of CAT activity was obtained
      in the presence of prolactin when the long form of the prolactin receptor was
      expressed, whereas no induction was observed when the short form was expressed.
      The present results clearly establish that only the long form of the prolactin
      receptor is involved in milk protein gene transcription.

PMID- 1992475
TI  - Drift, admixture, and selection in human evolution: a study with DNA
      polymorphisms.
AB  - Accuracy of evolutionary analysis of populations within a species requires the
      testing of a large number of genetic polymorphisms belonging to many loci. We
      report here a reconstruction of human differentiation based on 100 DNA
      polymorphisms tested in five populations from four continents. The results agree
      with earlier conclusions based on other classes of genetic markers but reveal
      that Europeans do not fit a simple model of independently evolving populations
      with equal evolutionary rates. Evolutionary models involving early admixture are
      compatible with the data. Taking one such model into account, we examined through
      simulation whether random genetic drift alone might explain the variation among
      gene frequencies across populations and genes. A measure of variation among
      populations was calculated for each polymorphism, and its distribution for the
      100 polymorphisms was compared with that expected for a drift-only hypothesis. At
      least two-thirds of the polymorphisms appear to be selectively neutral, but there
      are significant deviations at the two ends of the observed distribution of the
      measure of variation: a slight excess of polymorphisms with low variation and a
      greater excess with high variation. This indicates that a few DNA polymorphisms
      are affected by natural selection, rarely heterotic, and more often disruptive,
      while most are selectively neutral.

PMID- 1992474
TI  - Propeptide of a precursor to a plant vacuolar protein required for vacuolar
      targeting.
AB  - Sporamin is a protein without glycans that accumulates in large quantities in the
      vacuoles of the tuberous root of the sweet potato. It is synthesized as a prepro
      precursor with an N-terminal extension composed of a 21-amino-acid signal peptide
      and a 16-amino-acid propeptide. A total of 48 base pairs, corresponding to the
      nucleotide sequence that encodes the propeptide, was deleted from a cDNA clone
      for sporamin. This delta pro mutant sequence, as well as the sequence of the wild
      type sporamin cDNA, was placed downstream from the promoter of the 35S transcript
      from cauliflower mosaic virus and introduced into the genome of suspension
      cultured tobacco cells by Agrobacterium-mediated transformation. In contrast to
      the vacuolar localization of sporamin in cells that expressed the wild-type
      precursor, sporamin was secreted into the culture medium from cells in which the
      delta pro precursor was expressed. The secreted form of sporamin was shorter by
      two amino acids at its N terminus than authentic sporamin; it migrated
      anomalously during electrophoresis on SDS/polyacrylamide gel as a result of the
      presence of intramolecular disulfide bridges, as does authentic sporamin. The
      kinetics of secretion of sporamin from the cell were similar to those of proteins
      normally secreted by the host tobacco cells. These results indicate that the
      propeptide of the precursor to sporamin is required for correct targeting of
      sporamin to the vacuole and that proteins can be secreted from plant cells by a
      bulk-flow default pathway in the absence of a functional sorting signal.

PMID- 1992476
TI  - Inhibition of growth of experimental prostate cancer with sustained delivery
      systems (microcapsules and microgranules) of the luteinizing hormone-releasing
      hormone antagonist SB-75.
AB  - Inhibitory effects of the sustained delivery systems (microcapsules and
      microgranules) of a potent antagonist of luteinizing hormone-releasing hormone N
      Ac-[3-(2-naphthyl)-D-alanine1, 4-chloro-D-phenylalanine2, 3-(3-pyridyl)-D
      alanine3, D-citrulline6, D-alanine10]LH-RH (SB-75) on the growth of experimental
      prostate cancers were investigated. In the first experiment, three doses of a
      microcapsule preparation releasing 23.8, 47.6, and 71.4 micrograms of antagonist
      SB-75 per day were compared with microcapsules of agonist [D-Trp6]LH-RH
      liberating 25 micrograms/day in rats bearing Dunning R3327H transplantable
      prostate carcinoma. During 8 weeks of treatment, tumor growth was decreased by [D
      Trp6]LH-RH and all three doses of SB-75 as compared to untreated controls. The
      highest dose of SB-75 (71.4 micrograms/day) caused a greater inhibition of
      prostate cancer growth than [D-Trp6]LH-RH as based on measurement of tumor volume
      and percentage change in tumor volume. Doses of 23.8 and 47.6 micrograms of SB-75
      per day induced a partial and submaximal decrease, respectively, in tumor weight
      and volume. Tumor doubling time was the longest (50 days) with the high dose of
      SB-75 vs. 15 days for controls. The body weights were unchanged. The weights of
      testes, seminal vesicles, and ventral prostate were greatly reduced in all three
      groups that received SB-75, and testosterone levels were decreased to
      nondetectable values in the case of the two higher doses of SB-75. LH levels were
      also diminished. Similar results were obtained in the second experiment, in which
      the animals were treated for a period of 8 weeks with microgranules of SB-75.
      Therapy with microgranules of SB-75 significantly decreased tumor growth as
      measured by the final tumor volume, the percentage change from the initial tumor
      volume, and the reduction in tumor weight. The results indicate that antagonist
      SB-75, released from sustained delivery systems, can produce a state of chemical
      castration and effectively inhibit the growth of experimental prostate cancers.
      The efficacy of the antagonist SB-75 in inhibiting androgen-dependent Dunning
      prostatic carcinoma and the absence of side effects suggest its possible
      usefulness for the treatment of hormone-sensitive tumors.

PMID- 1992477
TI  - Expression of the bacterioopsin gene in Halobacterium halobium using a multicopy
      plasmid.
AB  - Bacteriorhodopsin (bR) was expressed in Halobacterium halobium by using a
      multicopy plasmid containing the bop gene. The plasmid contains pGRB1, a 1.8
      kilobase-pair plasmid; a 70-base-pair fragment from ISH11, a recently
      characterized insertion sequence; and a 1.6-kilobase-pair fragment carrying the
      bop gene from H. halobium S9. When transformed with this plasmid, a bop-
      insertion mutant of H. halobium yielded purple (Pum+) colonies. The insertion at
      the chromosomal bop locus remained intact in transformed cells, indicating that
      the plasmid bop gene was responsible for the Pum+ phenotype. bR was induced in
      early stationary phase in both wild-type and transformed cells. The final level
      of bR in transformed cells was 25-40% of that in wild type. The lower level of
      expression was presumably due to plasmid instability. Purple membrane purified
      from transformed strains had absorption and visible CD properties similar to wild
      type and contained bR in a hexagonal lattice with the same unit-cell dimension as
      wild type. The structure of bR from wild-type and transformed strains was
      identical at a resolution of 7.2 A. When reconstituted into vesicles, the purple
      membrane from wild-type and transformed strains showed similar light-dependent
      proton-pumping activity.

PMID- 1992478
TI  - Homologous recombination in Leishmania enriettii.
AB  - We have used derivatives of the recently developed stable transfection vector
      pALT-Neo to formally demonstrate that Leishmania enriettii contains the enzymatic
      machinery necessary for homologous recombination. This observation has
      implications for gene regulation, gene amplification, genetic diversity, and the
      maintenance of tandemly repeated gene families in the Leishmania genome as well
      as in closely related organisms, including Trypanosoma brucei. Two plasmids
      containing nonoverlapping deletions of the chloramphenicol acetyltransferase
      (CAT) gene, as well as the neomycin-resistance gene, were cotransfected into L.
      enriettii. Analysis of the DNA from these cells by Southern blotting and plasmid
      rescue revealed that a full-length or doubly deleted CAT gene could be
      reconstructed by homologous crossing-over and/or gene conversion between the two
      deletion plasmids. Additionally, parasites cotransfected with pALT-Neo and pALT
      CAT-S, a plasmid containing two copies of the chimeric alpha-tubulin-CAT gene,
      resulted in G418-resistant parasites expressing high levels of CAT activity. The
      structure of the DNA within these cells, as shown by Southern blot analysis and
      the polymerase chain reaction, is that which would be expected from a homologous
      exchange event occurring between the two plasmids.

PMID- 1992479
TI  - Molecular localization of the t(11;22)(q24;q12) translocation of Ewing sarcoma by
      chromosomal in situ suppression hybridization.
AB  - Chromosome translocations are associated with a variety of human leukemias,
      lymphomas, and solid tumors. To localize molecular markers flanking the t(11;22)
      (q24;q12) breakpoint that occurs in virtually all cases of Ewing sarcoma and
      peripheral neuroepithelioma, high-resolution chromosomal in situ suppression
      hybridization was carried out using a panel of cosmid clones localized and
      ordered on chromosome 11q. The location of the Ewing sarcoma translocation
      breakpoint was determined relative to the nearest two cosmid markers on 11q,
      clones 23.2 and 5.8, through the analysis of metaphase chromosome hybridization.
      By in situ hybridization to interphase nuclei, the approximate physical
      separation of these two markers was determined. In both Ewing sarcoma and
      peripheral neuroepithelioma, cosmid clone 5.8 is translocated from chromosome
      11q24 to the derivative chromosome 22 and a portion of chromosome 22q12 carrying
      the leukemia inhibitory factor gene is translocated to the derivative chromosome
      11. The physical distance between the flanking cosmid markers on chromosome 11
      was determined to be in the range of 1000 kilobases, and genomic analysis using
      pulsed-field gel electrophoresis showed no abnormalities over a region of 650
      kilobases in the vicinity of the leukemia inhibitory factor gene on chromosome
      22. This approach localizes the Ewing sarcoma breakpoint to a small region on
      chromosome 11q24 and provides a rapid and precise technique for the molecular
      characterization of chromosomal aberrations.

PMID- 1992480
TI  - Model for the structure of the lipid bilayer.
AB  - A detailed model for the structure and dynamics of the interior of the lipid
      bilayer in the liquid crystal phase is presented. The model includes two classes
      of motion: (i) the internal dynamics of the chains, determined from Brownian
      dynamics simulations with a continuous version of the Marcelja mean-field
      potential, and (ii) noncollective reorientation (axial rotation and wobble) of
      the entire molecule, introduced by a cone model. The basic unit of the model is a
      single lipid chain with field parameters adjusted to fit the 2H order parameters
      and the frequency-dependent 13C NMR T1 relaxation times of dipalmitoyl
      phosphatidylcholine bilayers. The chain configurations obtained from the
      trajectory are used to construct a representation of the bilayer. The resulting
      lipid assembly is consistent with NMR, neutron diffraction, surface area, and
      density data. It indicates that a high degree of chain disorder and entanglement
      exists in biological membranes.

PMID- 1992481
TI  - In vitro neurons in mammalian cortical layer 4 exhibit intrinsic oscillatory
      activity in the 10- to 50-Hz frequency range.
AB  - We report here the presence of fast subthreshold oscillatory potentials recorded
      in vitro from neurons within layer 4 of the guinea pig frontal cortex. Two types
      of oscillatory neurons were recorded: (i) One type exhibited subthreshold
      oscillations whose frequency increased with membrane depolarization and
      encompassed a range of 10-45 Hz. Action potentials in this type of neuron
      demonstrated clear after-hyperpolarizations. (ii) The second type of neuron was
      characterized by narrow-frequency oscillations near 35-50 Hz. These oscillations
      often outlasted the initiating depolarizing stimulus. No calcium component could
      be identified in their action potential. In both types of cell the subthreshold
      oscillations were tetrodotoxin-sensitive, indicating that the depolarizing phase
      of the oscillation was generated by a voltage-dependent sodium conductance. The
      initial depolarizing phase was followed by a potassium conductance responsible
      for the falling phase of the oscillatory wave. In both types of cell, the
      subthreshold oscillation could trigger spikes at the oscillatory frequency, if
      the membrane was sufficiently depolarized. Combining intracellular recordings
      with Lucifer yellow staining showed that the narrow-frequency oscillatory
      activity was produced by a sparsely spinous interneuron located in layer 4 of the
      cortex. This neuron has extensive local axonal collaterals that ramify in layers
      3 and 4 such that they may contribute to the columnar synchronization of activity
      in the 40- to 50-Hz range. Cortical activity in this frequency range has been
      proposed as the basis for the "conjunctive properties" of central nervous system
      networks.

PMID- 1992482
TI  - Thyrotropin-luteinizing hormone/chorionic gonadotropin receptor extracellular
      domain chimeras as probes for thyrotropin receptor function.
AB  - To define the sites in the extracellular domain of the human thyrotropin (TSH)
      receptor that are involved in TSH binding and signal transduction we constructed
      chimeric thyrotropin-luteinizing hormone/chorionic gonadotropin (TSH-LH/CG)
      receptors. The extracellular domain of the human TSH receptor was divided into
      five regions that were replaced, either singly or in various combinations, with
      homologous regions of the rat LH/CG receptor. The chimeric receptors were stably
      expressed in Chinese hamster ovary cells. The data obtained suggest that the
      carboxyl region of the extracellular domain (amino acid residues 261-418) and
      particularly the middle region (residues 171-260) play a role in signal
      transduction. The possibility is also raised of an interaction between the amino
      and carboxyl regions of the extracellular domain in the process of signal
      transduction. With respect to hormone binding, substitution of the entire
      extracellular domain of the LH/CG receptor for the corresponding region of the
      TSH receptor resulted in high-affinity human CG binding with complete loss of TSH
      binding. Surprisingly, however, there was at least one chimera with a
      substitution at each of the five domains that still retained high-affinity TSH
      binding. Substitution of residues 1-170 of the TSH receptor with the
      corresponding region of the LH/CG receptor was associated with the retention of
      high-affinity TSH binding but ligand specificity was lost in that TSH and human
      CG could interact functionally with the receptor. In summary, these studies
      suggest that the middle region and carboxyl half of the extracellular domain of
      the TSH receptor are involved in signal transduction and that the TSH-binding
      region is likely to span the entire extracellular domain, with multiple
      discontinuous contact sites.

PMID- 1992484
TI  - Kinetics of self-assembly of alpha alpha-tropomyosin coiled coils from unfolded
      chains.
AB  - The two-chain coiled-coil structural motif is found in fibrous muscle proteins
      and leucine zippers. Unfolding/refolding studies abound, but none establishes the
      time scale or mechanism of structural assembly from separated, unfolded chains.
      Stopped-flow circular dichroism studies of such refolding of alpha-tropomyosin
      chains are reported here. The backbone spectral region (222 nm) reveals a fast
      phase (less than 0.04 s), yielding an intermediate possessing approximately 70%
      of the equilibrium helix content. A subsequent slow phase is first order [k-1 (20
      degrees C) = 1.67 s, Ea = 12.7 kcal.mol-1 (1 kcal = 4.18 kJ)], so dimerization is
      fast. The same rate constant characterizes folding in the Cys-190 crosslinked
      chains, so the intermediate has parallel and nearly registered chains. The
      tyrosine spectral region (280 nm) reveals only a fast phase, so these six chain
      sites are native in the intermediate.

PMID- 1992483
TI  - Mutational activation of the c-Ha-ras gene in liver tumors of different rodent
      strains: correlation with susceptibility to hepatocarcinogenesis.
AB  - The frequency and pattern of mutations at codon 61 of the c-Ha-ras gene have been
      analyzed in 195 liver tumors and 132 precancerous liver lesions from various
      rodent strains with differing susceptibility to hepatocarcinogenesis. By using
      the polymerase chain reaction and allele-specific oligonucleotide hybridization,
      C----A transversions at the first base and A----T transversions or A----G
      transitions at the second base of c-Ha-ras codon 61 were detected in 20-60% of
      spontaneous or carcinogen-induced liver tumors of the C3H/He, CBA, CF1, and
      B6C3F1 mouse strains, which are highly susceptible to hepatocarcinogenesis. No
      such mutations, however, could be found in any of the 31 liver tumors of the
      insensitive C57BL/6J and BALB/c mouse strains or in any of the 35 liver tumors of
      the comparatively resistant Wistar rat. Further analyses of c-Ha-ras codon 12
      mutations in liver tumors from the three insensitive rodent strains also failed
      to give any positive results. In early precancerous liver lesions, c-Ha-ras codon
      61 mutations were found in 13-14% of lesions of the sensitive C3H/He and B6C3F1
      mouse strains but not in any of the 34 lesions of the insensitive C57BL/6J mouse.
      Taken together, our results indicate a close correlation between the mutational
      activation of the c-Ha-ras gene in liver tumors of the different rodent strains
      and their susceptibility to hepatocarcinogenesis, whereby the mutations appear to
      provide a selective growth advantage, leading to a clonal expansion of the
      mutated liver cell population, only in livers of sensitive but not of insensitive
      strains.

PMID- 1992485
TI  - CGG: an unassigned or nonsense codon in Mycoplasma capricolum.
AB  - CGG is an arginine codon in the universal genetic code. We previously reported
      that in Mycoplasma capricolum, a relative of Gram-positive eubacteria, codon CGG
      did not appear in coding frames, including termination sites, and tRNA(ArgCCG)
      pairing with codon CGG, was not detected. These facts suggest that CGG is a
      nonsense (unassigned and untranslatable) codon--i.e., not assigned to arginine or
      to any other amino acid. We have investigated whether CGG is really an unassigned
      codon by using a cell-free translation system prepared from M. capricolum.
      Translation of synthetic mRNA containing in-frame CGG codons does not result in
      "read-through" to codons beyond the CGG codons--i.e., translation ceases just
      before CGG. Sucrose-gradient centrifugation profiles of the reaction mixture have
      shown that the bulk of peptide that has been synthesized is attached to 70S
      ribosomes and is released upon further incubation with puromycin. The result
      suggests that the peptide is in the P site of ribosome in the form of peptidyl
      tRNA, leaving the A site empty. When in-frame CGG codons are replaced by UAA
      codons in mRNA, no read-through occurs beyond UAA, just as in the case of CGG.
      However, the synthesized peptide is released from 70S ribosomes, presumably by
      release factor 1. These data suggest strongly that CGG is an unassigned codon and
      differs from UAA in that CGG is not used for termination.

PMID- 1992486
TI  - Guanosine 5'-[beta-thio]triphosphate selectively activates calcium signaling in
      mast cells.
AB  - In rat peritoneal mast cells, the activation of GTP-binding proteins (G proteins)
      by guanosine 5'-[gamma-thio]triphosphate GTP[gamma S] has been found to induce a
      transient rise in intracellular calcium as well as degranulation. A G protein
      that couples to phospholipase C (Gp) is thought to mediate the calcium response,
      whereas degranulation is mediated by a different G protein, termed Ge. In an
      attempt to activate mast-cell G proteins more selectively, the GTP analogues
      guanosine 5'-[alpha-thio]triphosphate (GTP[alpha S]) and guanosine 5'-[beta
      thio]triphosphate (GTP[beta S]) (RP and SP diastereomers) were introduced into
      mast cells by means of patch pipettes. Degranulation and free intracellular
      calcium were monitored by cell capacitance and fura-2 measurements, respectively.
      It was found that RP-GTP[alpha S], like GTP[gamma S], induced both calcium
      release and exocytosis. In contrast, RP-GTP[beta S] induced repetitive calcium
      spikes that were not regularly accompanied by exocytosis. These results suggest
      that RP-GTP[beta S] selectively activates calcium signaling in mast cells. The RP
      GTP[beta S]-induced oscillations were independent of extracellular calcium. They
      were absent in the presence of heparin or high concentrations of inositol 1,4,5
      trisphosphate and modulated by compound 48/80, suggesting the involvement of the
      inositol phospholipid signaling pathway. Latency of appearance and spiking
      frequency were markedly modulated by varying the intracellular ATP concentration.
      The differential activation of intracellular calcium signaling and exocytosis by
      GTP[beta S] confirms the presence of independent signal-transduction pathways for
      the two cell responses. RP-GTP[beta S] may prove helpful in the biochemical and
      molecular characterization of Gp, the as-yet-unidentified G protein that couples
      receptors to intracellular calcium release.

PMID- 1992487
TI  - Molecular genetic basis for complex flagellar antigen expression in a triphasic
      serovar of Salmonella.
AB  - Strains of most Salmonella serovars produce either one (monophasic) or two
      (diphasic) antigenic forms of flagellin protein, but strains capable of
      expressing three or more serologically distinct flagellins ("complex" serovars)
      have occasionally been reported. A molecular genetic analysis of a triphasic
      strain of the normally diphasic serovar Salmonella rubislaw revealed that it has
      three flagellin genes, including the normal fliC (phase 1) and fljB (phase 2)
      chromosomal genes encoding type r and type e,n,x flagellins, respectively, and a
      third locus (herein designated as flpA) that is located on a large plasmid
      (pRKS01) and codes for a type d flagellin. The coding sequence of the plasmid
      borne gene is similar to that of a phase 1 chromosomal gene, but the sequence of
      its promoter region is homologous to that of a phase 2 chromosomal gene. The
      irreversible loss of the ability to express a type d flagellin that occurs when
      the triphasic strain is grown in the presence of d antiserum is caused by
      deletion of part or all of the flpA gene. Thus, the molecular basis for the
      unusual serological reactions of the triphasic strain of S. rubislaw and, by
      inference, other complex serovars of Salmonella is explained. Plasmids of the
      type carried by the triphasic strain of S. rubislaw provide a mechanism for the
      generation of new serovars through the lateral transfer and recombination of
      flagellin genes.

PMID- 1992489
TI  - Cloning of the DNA-binding subunit of human nuclear factor kappa B: the level of
      its mRNA is strongly regulated by phorbol ester or tumor necrosis factor alpha.
AB  - The DNA binding subunit of nuclear factor kappa B (NF-kappa B), a B-cell protein
      that interacts with the immunoglobulin kappa light-chain gene enhancer, has been
      purified from nuclei of human HL-60 cells stimulated with tumor necrosis factor
      alpha (TNF alpha), and internal peptide sequences were obtained. Overlapping cDNA
      clones were isolated and sequenced. The encoded open reading frame of about 105
      kDa contained at its N-terminal half all six tryptic peptide sequences,
      suggesting that the 51-kDa NF-kappa B protein is processed from a 105-kDa
      precursor. An in vitro synthesized protein containing most of the N-terminal half
      of the open reading frame bound specifically to an NF-kappa B binding site. This
      region also showed high homology to a domain shared by the Drosophila dorsal gene
      and the avian and mammalian rel (proto)oncogene products. The level of the 3.8
      kilobase mRNA was strongly increased after stimulation with TNF alpha or phorbol
      ester. Thus, both factors not only activate NF-kappa B protein, as described
      previously, but also induce expression of the gene encoding the DNA-binding
      subunit of NF-kappa B.

PMID- 1992488
TI  - Promotion of central cholinergic and dopaminergic neuron differentiation by brain
      derived neurotrophic factor but not neurotrophin 3.
AB  - Recombinant human brain-derived neurotrophic factor (rhBDNF) and neurotrophin 3
      (rhNT-3), two recently cloned molecules closely related to nerve growth factor
      (NGF), were produced from human cDNA expressed in human embryonic kidney cells.
      The recombinant proteins were tested in cultures of dissociated fetal rat brain
      cells containing basal forebrain cholinergic neurons. rhBDNF stimulated the
      differentiation of the cholinergic neurons, similar to NGF, which is well
      established as a neurotrophic factor for these cells. However, rhBDNF was
      particularly effective during the first few days in vitro, whereas the
      stimulatory action of rhNGF was more pronounced later in the development of the
      cultures. This finding indicates the existence of different time periods of
      responsiveness of the cholinergic neurons to BDNF and NGF. To assess the
      selectivity of the effect of rhBDNF on cholinergic neurons, its actions were
      tested in cultures of ventral mesencephalon containing dopaminergic cells. In
      contrast to NGF, which does not affect central dopaminergic neurons, rhBDNF
      increased dopamine uptake activity. The findings suggest that BDNF stimulates
      survival or differentiation of other cells besides the cholinergic neurons.

PMID- 1992490
TI  - Sequence determination and modeling of structural motifs for the smallest
      monomeric aminoacyl-tRNA synthetase.
AB  - Polypeptide chains of 19 previously studied Escherichia coli aminoacyl-tRNA
      synthetases are as large as 951 amino acids and, depending on the enzyme, have
      quaternary structures of alpha, alpha 2, alpha 2 beta 2, and alpha 4. These
      enzymes have been organized into two classes which are defined by sequence motifs
      that are associated with specific three-dimensional structures. We isolated,
      cloned, and sequenced the previously uncharacterized gene for E. coli cysteine
      tRNA synthetase (EC 6.1.1.16) and showed that it encodes a protein of 461 amino
      acids. Biochemical analysis established that the protein is a monomer, thus
      establishing this enzyme as the smallest known monomeric synthetase. The sequence
      shows that cysteine-tRNA synthetase is a class I enzyme that is most closely
      related to a subgroup that includes the much larger methionine-, isoleucine-,
      leucine-, and valine-tRNA synthetases, which range in size from 677 to 951 amino
      acids. The amino-terminal 293 amino acids of the cysteine enzyme can be modeled
      as a nucleotide-binding fold that is more compact than that of its closest
      relatives by virtue of truncations of two insertions that split the fold. This
      smaller nucleotide-binding fold accounts for much of the reduced size of the
      cysteine enzyme and establishes the limit to which the structure of this domain
      is contracted in the five members of this subgroup of class I enzymes.

PMID- 1992491
TI  - Peptide-induced antiviral protection by cytotoxic T cells.
AB  - A specific antiviral cytotoxic immune response in vivo could be induced by the
      subcutaneous injection of the T-cell epitope of the lymphocytic choriomeningitis
      virus (LCMV) nucleoprotein as an unmodified free synthetic peptide (Arg-Pro-Gln
      Ala-Ser-Gly-Val-Tyr-Met-Gly-Asn-Leu-Thr-Ala-Gln) emulsified in incomplete
      Freund's adjuvant. This immunization rendered mice into a LCMV-specific
      protective state as shown by the inhibition of LCMV replication in spleens of
      such mice. The protection level of these mice correlated with the ability to
      respond to the peptide challenge by CD8+ virus-specific cytotoxic T cells. This
      is a direct demonstration that peptide vaccines can be antivirally protective in
      vivo, thus encouraging further search for appropriate mixtures of stable peptides
      that may be used as T-cell vaccines.

PMID- 1992492
TI  - Toxaphene: chemistry, biochemistry, toxicity and environmental fate.
AB  - The chemistry of toxaphene is now well developed; 20 isomers have been isolated
      and identified. The molecular weight and molecular formula are known for the
      remaining major components. The major metabolic degradation mechanisms for
      toxaphene in all organisms from bacteria to primates are now believed to the
      reductive dechlorination, reductive dehydrochlorination, and in some cases,
      oxidative dechlorination to produce hydroxyl derivatives, acids or ketones.
      Earlier reports that toxaphene was biodegradable were published before the advent
      of state-of-the-art analytical methodology which has permitted detection at
      levels in the range of ppb. Toxaphene residues have recently been documented
      throughout the biosphere as well as in human milk, even though its use was banned
      in 1982. This global persistence is against previous beliefs that toxaphene was
      easily biodegradable. During the last decade advances have been achieved in the
      selectivity, accuracy, and sensitivity of detection techniques so that the
      presence of toxaphene throughout the biosphere has been extensively documented.
      Through the use of GC/MS and electron capture GC, toxaphene can now be detected
      at ppb levels, making possible a more consistent and accurate assessment of the
      compound's presence in organisms as well as in soil, water, and ground water.
      Toxaphene residues have been detected in human populations, fish and wildlife,
      soil, water, and ground water as well as in food. An FDA Food Survey study found
      residues of toxaphene exceeding regulatory limits in only 1% of the 14,492 food
      samples. Toxaphene was reported to be among the most frequently occurring
      residues found in total dietary foods for the period 1982-84. It was found 48
      times based on two food consumption surveys, a level higher than the frequency of
      DDT, DCPA, pentachloroaniline, and methoxychlor. Toxaphene has been detected in
      two large, pooled samples of human milk collected from mothers living in Uppsala
      and Stockholm at a concentration of 0.1 mg/kg of milk fat. Accumulation of
      toxaphene occurs in water in areas where the insecticide is in use, and it may be
      quite persistent. In some Canadian lakes it was found in toxic concentrations up
      to five yr after fish have been killed. Several studies have documented the
      presence of toxaphene in rain water, e.g. 9 ng/L in rain samples from Lake
      Michigan. It is now clear that toxaphene is a global pollutant like DDT, PCBs,
      and other organochlorines. Toxaphene is persistent in soils and lake sediments
      and has been found in fish, in the ringed seal, in rain water, and in human
      milk.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1992493
TI  - Pesticide residues in food crops analyzed by the California Department of Food
      and Agriculture in 1989.
AB  - California spends more than $40 million each year for the nation's most
      comprehensive program to regulate pesticide use: Pesticides are evaluated before
      they can be used. Businesses that sell or apply pesticides are licensed.
      Pesticide specialists enforce restrictions on pesticide use. Water, air, and soil
      are monitored for pesticide levels. And, as a final check in this integrated
      network of program, domestic and imported produce is sampled and tested for
      traces of pesticide residue. Annually, approximately 1% of the samples violate
      established standards. Because the standards include a safety margin, illegal
      residues rarely present a health risk, according to leading scientific experts,
      including the World Health Organization.

PMID- 1992494
TI  - Acute toxicology of components of vegetation smoke.
AB  - Only in recent times, systematic attention has been paid to the occupational
      health of forest firefighters and workers who manage prescribed fire. Two parts
      of the effort to learn the impact on worker health are medical observation of
      those workers, and study of occupational hygiene. It is also necessary to learn
      what components of smoke are most likely to affect firefighters, and to learn
      something of the manner in which those substances might compromise health; this
      review is a step toward that end. The number of possible products of vegetation
      combustion is almost limitless, and every fuel and condition of burning produces
      a unique pattern. Nonetheless, it is possible and practical to select a limited
      number of products that are most likely to be involved in the acute toxicity of
      smoke. Two products that are almost certainly important are formaldehyde and
      acrolein. Both appear to occur in all smoke. The toxicology of both is well
      studied; in particular both are powerful mucosal irritants. Estimates of exposure
      suggest strongly that concentrations are high enough in smoke to contribute some
      or all of the irritant activity. There seems to be a reasonable prospect that
      free radical precursors with half-lives in the tens of minutes are produced when
      cellulosic materials burn. If so, they will reach the respiratory tract, and
      liberate free radicals that react immediately on or in pulmonary cells. Ozone is
      not produced in the fire, but the various hydrocarbons of smoke are substrates
      for reactions that eventually produce ozone, and that production may continue for
      miles down-plume. Some measured plume concentrations approach the threshold for
      human health effects. The effects of the best known component, the particulate
      material, are unknown in isolation from all of the other substances in smoke. In
      spite of that ignorance, particulate loading is the principal index of smoke
      pollution for regulatory purposes, and sometimes is incorrectly used to represent
      smoke emissions regardless of source. The need to understand health impacts of
      these components of smoke seems obvious. Perhaps less obvious is the need to use
      such knowledge in management of both prescribed burning and wildfire. To some
      extent, it is possible to either manage fire itself to alter emission patterns,
      or control exposures in certain situations. Whether that should be done to
      protect worker health can only be judged if enough is known about health effects
      to direct the management decisions.

PMID- 1992495
TI  - Small mammals as monitors of environmental contaminants.
AB  - The merit of using small mammals as monitors of environmental contaminants was
      assessed using data from the published literature. Information was located on 35
      species of small mammals from 7 families used to monitor heavy metals,
      radionuclides, and organic chemicals at mine sites, industrial areas, hazardous
      and radioactive waste disposal sites, and agricultural and forested land. To
      document foodchain transfer of chemicals, concentrations in soil, vegetation, and
      invertebrates, where available, were included. The most commonly trapped North
      American species were Peromyscus leucopus, Blarina brevicauda, and Microtus
      pennsylvanicus. In these species, exposure to chemicals was determined from
      tissue residue analyses, biochemical assays, and cytogenetic assays. Where enough
      information was available, suitable target tissues, or biological assays for
      specific chemicals were noted. In general, there was a relationship between
      concentrations of contaminants in the soil or food, and concentrations in target
      tissues of several species. This relationship was most obvious for the
      nonessential heavy metals, cadmium, lead, and mercury and for fluoride. Kidney
      was the single best tissue for residue analyses of inorganic contaminants.
      However, bone should be the tissue of choice for both lead and fluorine. Exposure
      to lead was also successfully documented using biochemical and histopathological
      endpoints. Bone was the tissue of choice for exposure to 90Sr, whereas muscle was
      an appropriate tissue for 137Cs. For organic contaminants, exposure endpoints
      depended on the chemical(s) of concern. Liver and whole-body residue analyses, as
      well as enzyme changes, organ histology, genotoxicity, and, in one case,
      population dynamics, were successfully used to document exposure to these
      contaminants. Based on information in these studies, each species' suitability as
      a monitor for a specific contaminant or type of contaminant was evaluated and
      subsequently ranked. A relationship between contaminant exposure and trophic
      level emerged. Insectivores (shrews) had the highest levels of contaminants,
      followed by omnivores (cricetid mice) with intermediate levels, and herbivores
      (voles) with the lowest levels. A substantial number of these biomonitoring
      studies using small mammals collectively point to the importance of food habits
      and habitat of small mammals, and their availability and abundance as factors
      that should influence species selection for monitoring studies. The type of
      contaminants under consideration as well as the appropriateness of the endpoints
      selected are important factors to consider when deciding whether or not to
      include small mammals in biomonitoring studies.

PMID- 1992496
TI  - [What is your roentgen diagnosis? Postoperatively swallowed foreign body in a
      state of confusion].

PMID- 1992497
TI  - [TIA--an emergency?].
AB  - Transient ischemic attacks (TIA) can be a sign of impending stroke and as such an
      indication of atherosclerotic disease or other impending vascular catastrophe. We
      discuss clinical presentation, pathophysiologic mechanisms, diagnostic procedures
      and guidelines for therapy using data from four TIA cases sharing certain
      symptoms but differing in etiology.

PMID- 1992498
TI  - [The drug abuse patient as emergency].
AB  - Acute drug intoxication is a medical emergency considering its potential
      interference with vital functions. All 157 cases with drug overdose admitted to
      the emergency department of the "Inselspital" in Berne over 183 days between July
      1989 and June 1990 were analyzed retrospectively. In the vast majority of cases
      heroin overdose was involved. In mixed poisonings with heroin mostly
      flunitrazepam and alcohol contributed to the clinical picture, less commonly
      cocaine. There were very few intoxications with cocaine alone. A practical
      approach to the management of patients with certain or suspected drug
      intoxication presenting with coma and depressed respiration is proposed. In the
      therapy of acute intoxications with opiates and benzodiazepines there are
      specific antagonists available. In contrast, therapy of cocaine overdose remains
      symptomatic. The medical complications of acute heroin and cocaine intoxications
      are discussed separately.

PMID- 1992499
TI  - [Unstable angina pectoris].
AB  - Unstable angina pectoris, a particular form of acute coronary heart disease is
      described in two exemplary cases. This article will illustrate problems with
      definition and further (sub-)classification of the disease. Furthermore etiology
      and pathophysiologic mechanisms as well as diagnostic tools, current management
      and prognostic aspects will be discussed.

PMID- 1992500
TI  - [Hyperkalemia].
AB  - In two cases with drug-related hyperkalemia, potassium homeostasis, causes,
      symptoms and therapy are discussed. Iatrogenic and therefore avoidable
      hyperkalemia occurs most often when potassium, ACE-inhibitors, nonsteroidal
      antiinflammatory drugs or potassium-sparing diuretics are administered in
      patients with impaired renal function or diabetes mellitus. The emergency
      treatment in patients with severe hyperkalemia consists of intravenous calcium
      injections, infusion of glucose with insulin and, more recently, salbutamol. With
      acidotic patients administration of sodium-bicarbonate can be tried. Ion-exchange
      drugs and furosemide have a more delayed effect. With oliguria and anuria
      hemodialysis is often necessary.

PMID- 1992501
TI  - [Transfusion-associated HIV infections in Switzerland 1982-1989].
AB  - Up to summer 1987, 19 patients who had acquired HIV infection by blood
      transfusion had been recorded in Switzerland. In the subsequent period, up to
      1989, a further 15 patients with transfusion-associated HIV infection were
      recorded. In December 1989, 7 of these patients were asymptomatic, 4 had ARC, 5
      Aids and 11 had died of Aids. One patient died of another disease and no detailed
      records were available in 6. It is estimated that some 170 persons may have been
      infected with HIV by transfusion in Switzerland before anti-HIV testing was
      introduced in fall 1985. Of these only 31% (20%) are recorded today. The average
      incubation time from infection to diagnosis of Aids was 54 months. The 11
      patients who died of Aids had mean survival of 57 months after diagnosis of the
      disease. In 6 instances HIV-infected blood recipients have transmitted the
      disease to their sexual partners.

PMID- 1992503
TI  - [Psychiatric catamnesis in patients with restless legs].
AB  - In a follow-up study patients with "restless legs" investigated in 1986 were
      reexamined three years later. In 1989 the patients showed similar
      psychopathological symptoms, i.e. a depressive-anxious-hypochondric syndrome. The
      connection between restless legs syndrome and psychic disorders, and in
      particular the possibility of a common pathogenesis, are discussed.

PMID- 1992502
TI  - [HIV infection and syphilis. Case description and literature review].
AB  - Recent case reports emphasize that HIV infection may influence the clinical
      picture, course and therapy of concurrent syphilis. The case of a 32-year-old
      patient with coinfection by T. pallidum and HIV is presented. Clinical
      presentation, diagnostic procedures and therapy are discussed in the light of the
      current literature. False negative serologic tests for syphilis in HIV-patients
      raise the question of the sensitivity of these tests in HIV infection. Efficacy
      of therapy for neurosyphilis and the value of CSF (cerebrospinal fluid)
      examination in early syphilis are of increased importance in HIV infection.
      Current guidelines for diagnosis and therapy of syphilis in HIV patients are
      outlined.

PMID- 1992505
TI  - Gene rush. Companies seek profits in the genome project.

PMID- 1992504
TI  - [Acute transverse myelitis in systemic lupus erythematosus: successful therapy
      with cyclophosphamide and prednisone].
AB  - We describe a patient with acute transverse myelitis as the first symptom of
      systemic lupus erythematosus who was successfully treated with cyclophosphamide
      and prednisone. The literature on transverse myelitis is reviewed and its
      clinical presentation, diagnosis, therapy and prognosis are discussed. A new
      therapeutic approach involving cyclophosphamide and prednisone is proposed.

PMID- 1992506
TI  - DNA fingerprinting.

PMID- 1992507
TI  - Trans fat. Does margarine really lower cholesterol?

PMID- 1992508
TI  - Profile: AIDS dispute.

PMID- 1992509
TI  - The protein folding problem.

PMID- 1992510
TI  - Federal impediments to scientific research.

PMID- 1992512
TI  - Science budget: growth amid red ink.

PMID- 1992511
TI  - Carcinogens and human health: Part 3.

PMID- 1992513
TI  - Is UK HIV strain really LAV?

PMID- 1992514
TI  - Pinning down Gallo's virus.

PMID- 1992515
TI  - Did Turing discover how the leopard got its spots?

PMID- 1992516
TI  - New hope for vaccine against schistosomiasis.

PMID- 1992517
TI  - Graphite: a mimic for DNA and other biomolecules in scanning tunneling microscope
      studies.
AB  - Highly ordered pyrolytic graphite (HOPG) is the substrate often used in scanning
      tunneling microscope (STM) studies of biomolecules such as DNA. All of the images
      presented in this article are of freshly cleaved HOPG surfaces upon which no
      deposition has occurred. These images illustrate features previously thought to
      be due to biological molecules, such as periodicity and meandering of "molecules"
      over steps. These features can no longer be used to distinguish real molecules
      from features of the native substrate. The feasibility of the continued use of
      HOPG as a substrate for biological STM studies is discussed.

PMID- 1992518
TI  - Large protein-induced dipoles for a symmetric carotenoid in a photosynthetic
      antenna complex.
AB  - Unusually large electric field effects have been measured for the absorption
      spectra of carotenoids (spheroidene) in the B800-850 light-harvesting complex
      from the photosynthetic bacterium Rhodobacter sphaeroides. Quantitative analysis
      shows that the difference in the permanent dipole moment between the ground state
      and excited states in this protein complex is substantially larger than for pure
      spheroidene extracted from the protein. The results demonstrate the presence of a
      large perturbation on the electronic structure of this nearly symmetric
      carotenoid due to the organized environment in the protein. This work also
      provides an explanation for the seemingly anomalous dependence of carotenoid band
      shifts on transmembrane potential and a generally useful approach for calibrating
      electric field-sensitive dyes that are widely used to probe potentials in
      biological systems.

PMID- 1992519
TI  - The histiocytic syndromes. Introduction.

PMID- 1992520
TI  - Liver transplantation in Langerhans' cell histiocytosis (histiocytosis X).
AB  - Two children with biopsy-proven LCH underwent successful hepatic transplantation
      for end-stage liver disease. These patients were thought not to have active LCH
      disease at the time of transplantation, although one had developed a new
      osteolytic lesion a few months before the operation and the other had suspicious
      osteolytic lesions at the time of transplantation. The histologic examination of
      the excised liver showed features consistent with primary sclerosing cholangitis.
      The two patients had an excellent recovery with no evidence of progression of LCH
      or recurrence of the underlying disease in the hepatic allograft at 1 and 3 years
      after organ transplantation.

PMID- 1992521
TI  - Diagnostic guidelines for hemophagocytic lymphohistiocytosis. The FHL Study Group
      of the Histiocyte Society.

PMID- 1992522
TI  - Familial erythrophagocytic lymphohistiocytosis.
AB  - FEL is an autosomal recessive, lethal disease of early childhood characterized by
      hepatosplenomegaly, fever, and multisystem lymphohistiocytic infiltrates. The
      etiology and pathogenesis of this disorder remain uncertain. However, evidence
      suggests that the disease may be due to an inherited defect in immunoregulation
      that predisposes to an uncontrolled proliferation of activated histiocytes in
      response to a stimulus such as viral infection. Although clinical remission can
      often be achieved with systemic VP-16 and aggressive CNS therapy, the disease
      usually becomes refractory to treatment with a fatal outcome. Bone marrow
      transplantation may prove to be an effective treatment for this tragic disease.

PMID- 1992523
TI  - True histiocytic lymphoma.
AB  - It is likely that a significant number of cases of THL will continue to be
      misdiagnosed unless appropriate cytochemical and immunologic markers are
      incorporated into the panel of studies performed at diagnosis. The clinical
      findings are nonspecific. With the possible exception of skin infiltration, the
      frequency of symptoms and signs appear to approximate those of intermediate grade
      lymphomas. Most commonly, it is the histopathological features that suggest the
      histiocytic nature of a malignant process, but these alone are not sufficient to
      secure the diagnosis. Thus, in the absence of a clearly defined lymphoid origin,
      it is the detection of specific histiocytic markers that establishes a lymphoma
      as THL. Only the recognition and careful study of additional cases will
      potentially enable clinical investigators to identify any unique characteristics
      and distinguish this disease from other lymphomas. For the present, it would
      appear that the treatment indicated for a patient with diffuse large cell
      lymphoma would also be appropriate for a comparable patient with THL. Although
      long-term disease-free survival in THL is possible, there are presently
      inadequate data to estimate curability.

PMID- 1992524
TI  - Diffuse "histiocytic" lymphoma.

PMID- 1992525
TI  - Morphologic findings in the histiocytic syndromes.

PMID- 1992526
TI  - Advances in the management of gastrointestinal malignancies.
AB  - Although progress in treating gastrointestinal (GI) malignancies has been slow,
      several new approaches have resulted in increased response rates and, in some
      cases, improved survival. A greater understanding of the etiology of GI cancers
      makes possible the prevention of many of these tumors. New diagnostic tools,
      including endoscopic ultrasound, the CA19-9 radioimmunoassay, and the
      carcinoembryonic antigen assay, have improved clinicians' ability to detect early
      stage and recurrent disease. Efforts to enhance response to fluorouracil (5-FU)
      in the treatment of colorectal cancer by the addition of various immunologic or
      biochemical modulators have yielded encouraging results. Combinations of 5-FU
      with levamisole, interferon alfa, leucovorin, methotrexate, or N-(phosphonacetyl)
      L-aspartate have resulted in significant increases in response rates and, in the
      case of 5-FU/levamisole, increased survival. Promising results have also been
      obtained in the treatment of pancreatic cancer with a combination regimen of
      monoclonal antibodies (MoAbs) plus chemotherapy (5-FU/doxorubicin/mitomycin) and
      in the treatment of hepatocellular cancer with an antiferritin MoAb/radioisotope
      conjugate. Finally, the addition of interferon alfa to 5-FU has produced improved
      response rates in preliminary trials in patients with esophageal cancer. Other
      strategies, such as attempts to enhance MoAb activity in the treatment of
      pancreatic cancer, may prove productive as well and are currently being explored
      in laboratory and clinical studies.

PMID- 1992527
TI  - Current treatment approaches in colorectal cancer.
AB  - Fluorouracil (5-FU) is still the mainstay of adjuvant treatment for colorectal
      cancer. Two trials have shown a disease-free and overall survival benefit for 5
      FU combined with levamisole in patients with node-positive colon cancer. This
      regimen is fairly well tolerated and devoid of long-term sequelae, and is now
      considered standard treatment for node-positive colon cancer. One trial showed a
      modest improvement in disease-free survival for the semustine/vincristine/5-FU
      combination; the leukemogenicity and renal toxicity caused by semustine have
      prevented this regimen from being adopted. Although administering 5-FU directly
      into the portal vein may improve disease-free survival, most trials have failed
      to demonstrate a reduction in the incidence of hepatic metastases. This
      technique, therefore, remains investigational. Several trials in rectal cancer
      show an advantage for 5-FU combined with semustine and radiation therapy in terms
      of disease-free survival, overall survival, or both; the contribution of
      semustine has been questioned and is currently being investigated. In patients
      with metastatic disease, hepatic arterial infusion of floxuridine produces a
      higher objective response rate than intravenous administration, but has not
      resulted in a survival benefit; hepatobiliary toxicity limits the duration of
      therapy. Biochemical modulation of 5-FU with leucovorin increases the response
      rate produced by 5-FU alone; a survival benefit has also been observed. N
      (phosphonacetyl)-L-aspartate has shown initial promise in combination with high
      dose 5-FU infusions. Among the many new drugs tested, only tauromustine seems
      worthy of further study.

PMID- 1992528
TI  - The role of immunotherapy in colorectal cancer.
AB  - Despite landmark advances in the molecular biology and surgical adjuvant therapy
      of colorectal cancer in the past decade, this illness remains a significant
      health hazard. Conventional therapies, including surgery, radiation therapy, and
      chemotherapy, have had limited utility and have often resulted in unacceptable
      host toxicities. Therapies dependent on potentiation of the host immune response
      are attractive alternatives to conventional treatment because of their greater
      specificity and diminished toxicity. Furthermore, the efficacy of many of these
      therapies has been demonstrated in preclinical models, which is important given
      the relative refractoriness of colorectal cancer to chemotherapy. Both active
      specific therapies, such as tumor vaccines, and passive therapies, such as
      monoclonal antibodies, have been investigated. In early clinical trials, both
      have demonstrated modest activity. Nonspecific immune stimulation with agents
      such as bacillus Calmette-Guerin or methanol extraction residue appear to have
      little utility, but with the development of recombinant DNA technology, specific
      cytokines with more precisely identified targets have been synthesized in
      sufficient quantities for clinical trials. Finally, combinations of biologics or
      combinations of biologics with conventional therapies, such as fluorouracil (5
      FU)/levamisole and 5-FU/interferon, have been investigated and appear to be
      useful in the treatment of surgically resected and advanced colorectal carcinoma,
      respectively. The utility of these therapies is hampered by a limited
      understanding of their precise mechanisms of action and optimal conditions for
      administration. Nevertheless, immunotherapy of colorectal carcinoma remains an
      important and promising area for further clinical investigation.

PMID- 1992529
TI  - Implications of current therapeutic approaches in colorectal cancer for other
      gastrointestinal malignancies.
AB  - Novel immunotherapeutic strategies for combating colon cancer are also being
      explored in pancreatic, hepatic, and esophageal cancers. Preliminary clinical
      trials in patients with pancreatic cancer suggest a therapeutic role for anti
      idiotypic antibodies against tumor-specific monoclonal antibodies (MoAbs)--eg,
      CO17-1A, BW 494/32--but not for MoAbs when used alone. Adding low doses of
      interferon gamma to CO17-1A enhances in vitro antibody-dependent cellular
      cytotoxicity against pancreatic tumor cells; CO17-1A plus a regimen of 5
      FU/doxorubicin/mitomycin has resulted in beneficial therapeutic effect.
      Treatments with immunotoxins, radiolabeled MoAbs, and adoptive immunotherapy are
      still being tested preclinically. In 105 patients with unresectable
      hepatocellular cancer, a 7% complete and 41% partial regression rate with 131I
      labeled antiferritin has been reported. In several patients, radiolabeled
      antiferritin caused sufficient shrinkage of lesions to permit curative resection.
      Pretreatment with low-dose doxorubicin may improve the efficacy of low-dose
      radiolabeled antiferritin antibody therapy. Chemoembolization of primary
      hepatocellular carcinoma, based on the concept of regional therapy for metastatic
      colorectal cancer, has shown considerable palliative and survival benefit in
      patients with unresectable disease. Although adoptive immunotherapy has been used
      to treat hepatocellular carcinoma, the results have been disappointing. The
      development of immunotherapeutic approaches to esophageal cancer is less advanced
      than that for other gastrointestinal malignancies. Paralleling the successful use
      of 5-FU/interferon alfa-2a in colon cancer are two phase II studies that have
      evaluated this combination in patients with locally advanced esophageal cancer.
      The objective response rate (27%) was encouraging.

PMID- 1992530
TI  - Diagnosis and prevention of gastrointestinal malignancies.
AB  - The consistently high mortality rates associated with gastrointestinal cancer
      result in large part from malignancies that progress undetected to an advanced
      stage of disease when treatment is usually less effective. In response to this
      fact, increasing attention has been directed toward developing methods of both
      primary and secondary prevention of malignancies. Advances in primary prevention
      have resulted in a better understanding of various etiologic factors in the
      environment that are related to carcinogenesis and how they can be corrected or
      eliminated. Advances in secondary prevention have improved efforts to identify
      and eradicate the premalignant stages of gastrointestinal cancer before lethal
      consequences can develop. Refinements in screening methods and improvements in
      diagnostic procedures, such as the introduction of endoscopic ultrasound, will
      allow physicians to detect gastrointestinal cancers and their premalignant
      forerunners at an earlier stage in an effort to render treatment strategies more
      effective.

PMID- 1992531
TI  - Carboplatin plus radiation therapy in head and neck cancer.
AB  - To determine toxicity and response, escalating dose levels of carboplatin were
      given simultaneously with accelerated radiation to 36 previously untreated
      patients with unresectable squamous cell carcinomas of the head and neck (SCCHN)
      (2 with stage III and 34 with stage IV disease). Twenty-three patients received a
      total radiation dose of 58.8 Gy with two daily fractions of 2.1 Gy on days 1
      through 4 in weeks 1, 2, and 5 and on two additional days in week 6. Simultaneous
      carboplatin was given intravenously at escalating dose levels: 20 mg/m2 in 3
      patients, 30 mg/m2 in 5 patients, 40 mg/m2 in 5 patients, 50 mg/m2 in 6 patients,
      and 60 mg/m2 in 4 patients. Another 13 patients were treated with an escalated
      radiation dose of 67.2 Gy, which resulted in 2 more days of radiochemotherapy in
      week 6. Six patients in this group received 60 mg/m2/d and 7 received 50 mg/m2/d
      carboplatin. All patients were evaluable for toxicity according to World Health
      Organization (WHO) criteria and 35 of 36 patients were evaluable for response.
      Dose-limiting toxicity was myelosuppression with WHO grades 3 and 4 leukopenia in
      5 of 6 patients treated with 60 mg/m2 carboplatin and 67.2 Gy. With
      radiochemotherapy doses of 67.2 Gy and 50 mg/m2, no grade 4 myelosuppression
      occurred and toxicity was generally tolerable. Independent of the carboplatin
      dose, mucositis grade 3 or 4 was seen in 12 patients. No other toxicities above
      WHO grade 2 occurred, except in 2 patients with grade 3 nausea and vomiting.
      There were 19 complete responses (53%) and 16 partial responses (44%). Our
      preliminary data suggest that 50 mg/m2 carboplatin together with a total
      radiation dose of 67.2 Gy might be the best combination for advanced,
      unresectable SCCHN.

PMID- 1992532
TI  - Phase II study of carboplatin in advanced breast cancer: preliminary results.
AB  - The antitumor activity of carboplatin (400 mg/m2 intravenously every 4 weeks) in
      advanced breast cancer was evaluated in two consecutive trials enrolling patients
      with and without prior exposure to chemotherapy, respectively. All patients had
      measurable disease in at least one site. The first trial included patients who
      had received prior chemotherapy (adjuvant, neoadjuvant, or chemotherapy for
      metastatic disease). All but one of these patients had previously received
      doxorubicin-containing combinations. There were no objective responses among the
      first 14 evaluable patients, although 7 of them had stable disease, including 2
      with minor responses. The second trial, carried out with patients who had no
      prior exposure to chemotherapy, is ongoing. Currently, 6 of 19 evaluable patients
      have obtained a complete (1) or partial (5) response to carboplatin, resulting in
      an overall response rate of 32%. In both studies, toxicity was mild, mainly
      consisting of emesis (88%), leukopenia (22%), and thrombocytopenia (12%). Thus,
      by standard criteria, carboplatin was not found to be active in breast cancer
      patients with prior exposure to chemotherapy. Preliminary results in patients
      without such exposure are encouraging, although additional patients are needed to
      confirm these data.

PMID- 1992533
TI  - The costs of carboplatin treatment.
AB  - Safety and efficacy trials comparing carboplatin and cisplatin, especially in
      ovarian cancer, have shown that the two drugs have a similar efficacy profile.
      Carboplatin, however, is significantly less toxic than cisplatin. The total costs
      of carboplatin and cisplatin therapy, which include not only drug costs but all
      health care costs incurred in preventing and managing toxicity, therefore differ
      considerably. Thus, despite carboplatin's considerably more expensive cost per
      dose, when the total costs of treatment are considered, carboplatin treatment is
      certainly no more expensive, and in many countries may be less expensive, than
      cisplatin therapy.

PMID- 1992534
TI  - Megestrol acetate in cancer cachexia.
AB  - This randomized, controlled trial assessed the activity, tolerance, and degree of
      weight gain and anorexia of two doses of megestrol acetate in patients with
      advanced cancer and cachexia. Patients received either 480 mg/d or 960 mg/d
      megestrol acetate or placebo for 8 weeks. As of June 1990, 55 patients had been
      randomized; 16 died during the 8-week study, and it was too early to evaluate
      another 5 patients. The remaining 34 patients were included in analyses. The
      median initial weight loss ranged from 15% to 22% of usual body weight, which
      shows the severe degree of malnutrition. Further weight loss was seen in 6 of 8
      patients in the placebo group compared with only 5 of 15 and 3 of 11 patients in
      the low-dose and high-dose megestrol acetate groups, respectively. The median
      further weight loss was comparable in all groups. Six of 15 and 6 of 11 patients
      in the low-dose and high-dose groups, respectively, gained weight with a median
      of 3 kg and 4 kg, respectively. A trend showed beneficial effects of megestrol
      acetate. Appetite improvement was similar in all groups. Due to the small sample
      size, however, there were no statistically significant differences among the
      three groups. Side effects of megestrol acetate were mild. In a subgroup of 15
      patients, measurement of body water content indicated a decrease of body fat
      after 8 weeks in the placebo and low-dose groups. Only the high-dose megestrol
      acetate group showed an increase in both fat and lean body mass, suggesting a
      positive effect.

PMID- 1992535
TI  - Treatment of anorexia and weight loss with megestrol acetate in patients with
      cancer or acquired immunodeficiency syndrome.
AB  - Anorexia is a symptom of cancer and a cause of decreased caloric intake and
      weight loss. Successful treatment for anorexia can improve the patient's well
      being and prevent or reverse the effects of anorexia on nutrition. Following
      reports of appetite enhancement and weight gain in uncontrolled studies of high
      dose (320 to 1,600 mg/d) megestrol acetate in patients with cancer or AIDS
      (acquired immunodeficiency syndrome), several randomized, placebo-controlled
      trials have been completed. These trials demonstrate that megestrol acetate
      therapy improves appetite and food intake in patients with anorexia and advanced
      cancer, leading to weight gain in a subset of patients. The mechanisms of action
      of megestrol acetate (a progesterone derivative) probably include both behavioral
      and metabolic effects. Several carefully designed randomized trials are under way
      to establish the optimal dose and to determine the mechanism of weight gain.
      Patients with cancer or AIDS who complain of anorexia and whose nutritional
      status is compromised may benefit from megestrol acetate therapy.

PMID- 1992536
TI  - Etoposide in the management of leukemia: a review.
AB  - Single-agent etoposide (VP16-213, NSC 141540) induces complete response (CR) in
      15% to 25% of previously treated patients with acute nonlymphocytic leukemia
      (ANLL). Etoposide has been used successfully in combination with cytarabine,
      daunorubicin, and amsacrine as salvage and consolidation therapy. Patients aged
      15 to 70 years with previously untreated ANLL were randomized to therapy with
      either 7-3 (cytarabine 100 mg/m2/d days 1 to 7 and daunorubicin 50 mg/m2/d days 1
      to 3) or 7-3-7 (7-3 plus etoposide 75 mg/m2/d days 1 to 7). Patients achieving CR
      received two consolidation courses of the same drugs for shorter duration (5-2 or
      5-2-5). Of 264 eligible patients, 7-3 induced CR in 56%, 7-3-7 in 59%. Remission
      duration was significantly improved with 7-3-7 (median, 12 months 7-3, 18 months
      7-3-7, P = .01) but not survival. Subset analysis in patients under 55 years of
      age revealed prolonged remission (median, 12 months 7-3 v 27 months 7-3-7, P =
      .01) and survival (median, 9 months 7-3 v 17 months 7-3-7, P = .04) with 7-3-7.
      Hematologic toxicity was similar during induction but significantly more severe
      in consolidation. Etoposide is active in ANLL and prolongs remission when used as
      induction therapy.

PMID- 1992538
TI  - [Computerized tomography of the female thorax after mastectomy: the most
      important topometric data from the viewpoint of radiation].
AB  - The author analysed postoperative CT images of 77 patients operated on carcinoma
      of the breast and performed topometric measurements on the level of
      sternoclavicular joints parasternal, and in the centre line of the sternum in the
      height of the second and sixth intercostal space as well as on the thorax wall
      medioclavicular and on the forepart of the axillar line. The values measured
      corresponded to the literary data in general except those of the second
      intercostal space and of the axilla. The author stresses the necessity of CT
      series when making radiation planning of breast cancer.

PMID- 1992537
TI  - [Radiotherapy of primary vaginal carcinoma and effects of histological and
      clinical factors on the prognosis].
AB  - 434 cases of primary vaginal carcinoma were treated from 1950 to 1984 at the
      Irradiation Department of the University Clinic for Obstetrics and Gynecology,
      Vienna. The five-year survival rate for various clinical stages is as follows:
      Stage I 76.7%, stage II 44.5%, stage III 31%, stage IV 18.2%. In this
      retrospective study 110 patients seen from 1975 to 1984 were reviewed in detail
      and evaluated with a view toward their clinical and morphological aspects and
      survival rates. Patients up to the age of 60 have a five-year survival rate of
      50%, those over 75 years of age reach only 34.3%. If the carcinoma was discovered
      in a routine check up the survival rate is 61.1%, whereas in cases with symptoms
      the rate decreases to 36.9%. Survival differences were also observed for patients
      with a carcinoma in the upper third of the vagina (61.1%) versus patients with a
      carcinoma in the lower third (33.3%); for patients with well-differentiated
      tumours (62.5%) versus patients with grades II and III (41.5% and 34.9%). It can
      be seen, that with brachytherapy local control of the carcinoma can be achieved
      with excellent results in early stages. Treatment of patients with more advanced
      carcinomas should include external beam therapy. The importance of gynecological
      screening especially for older women is emphasized.

PMID- 1992539
TI  - Radiotherapy of the rhabdomyosarcoma R1H of the rat: split-course versus
      continuous fractionation.
AB  - Fractionated split-course treatments were given with gaps of different length and
      the effects on tumor response was studied using the rhabdomyosarcoma R1H of the
      rat. Total doses of 68, 75 and 82 Gy were applied in 30 fractions (five fractions
      per week). After four weeks, that is after 20 fractions, treatment was
      interrupted for one or two weeks followed by another ten fractions. The results
      were compared to those of continuous treatment given in six consecutive weeks.
      Tumor response was quantified by TCD37% and net growth delay. The TCD37%
      increased with increasing duration of the gap. A mean repopulated dose of 0.72 Gy
      per day was obtained. This corresponds to a doubling time of tumor clonogens of
      4.2 days during the gap, which is somewhat slower than the volume doubling time
      of unperturbed tumors (2.5 days) of the same size. The results obtained for the
      net growth delay support the results of the TCD37% data. It is concluded that a
      gap during fractionated radiotherapy leads to poorer results since the dose
      required for tumor control is enhanced and sparing of normal tissue can only be
      expected for early but not for late reacting tissues.

PMID- 1992540
TI  - [Hormone receptor contents and tumor growth in a series of transplantable human
      breast carcinoma during and after radiotherapy].
AB  - The influence of radiotherapy on tumor growth and hormone receptor concentration
      (estrogen-, progesteron-receptor) in xenotransplanted human breast cancer is
      observed. Tumor growth significantly is delayed under therapy during the first 35
      days after radiation. Renewed growth follows after that time. After the first
      days of treatment the ER and PR concentration decreases considerably and finally
      reaches 40% respectively 30% of the pretreatment level for a period of
      approximately 35 days after the end of radiotherapy. In general radiation therapy
      seems to affect the PR stronger than the ER. After this period ER and PR levels
      increase again with the regrowing tumor. The results point out that radiotherapy
      reduces the concentration of ER and PR in human breast cancer. Therefore the
      assay of steroid receptors in human breast cancer after radiation therapy is
      useful in predicting hormone dependency and prognosis only when receptor
      concentrations are positive.

PMID- 1992541
TI  - Differences in repair of radiation induced damage in two human tumor cell lines
      as measured by cell survival and alkaline DNA unwinding.
AB  - We studied the relationship between the repair of radiation induced DNA strand
      breaks and cellular repair kinetics in two human tumor cell lines, NB-100
      (neuroblastoma) and HN-1 (squamous cell carcinoma). Damage was quantified using
      the fluorometric analysis of DNA unwiding (FADU) for DNA damage, and cell
      survival was assessed using a clonogenic assay. In plateau phase cells repair of
      sublethal damage was virtually absent in NB-100 after 4 Gy (recovery ratio 1.0),
      whereas HN-1 cells did show sublethal damage repair (recovery ratio 1.4). Repair
      of potentially lethal damage was more pronounced in NB-100 cells (recovery ratio
      2.3) than in HN-1 cells (recovery ratio 1.7) after 4 Gy. Graded doses of X-rays
      induced comparable levels of DNA damage in both tumor cell lines. However, in HN
      1 cells more DNA strand breaks were repaired after 4 Gy, leaving about 25% of the
      initial damage unrepaired, whereas in NB-100 about 50% was unrepaired. This
      higher fraction of unrepaired DNA damage correlated well with the degree of
      sublethal damage repair which was lower in NB-100 than in HN-1 cell, but it did
      not correlate with the repair of potentially lethal damage, which was higher in
      NB-100 than in HN-1. Since the level of damage remaining post-irradiation may be
      the critical variable for survival, the FADU technique can contribute in
      elucidating the relationship between radiosensitivity and DNA damage repair
      capacity.

PMID- 1992542
TI  - Effect of age on the radiation-induced repopulation in mouse lip mucosa.
AB  - The acute macroscopic radiation reactions in mouse lip mucosa were used as a
      biological model to evaluate the influence of aging on the radiosensitivity and
      more specifically on the repopulation capacity after irradiation of rapidly
      proliferating epithelial tissues. No difference in the mucosa response after
      single dose irradiations was observed for animals ranging between one and twelve
      months of age. There was a trend for decreased radiosensitivity of the lip mucosa
      comparing 18 months old (early-senescence) with young adult mice. The
      repopulation experiments involved two equal sized radiation doses delivered with
      an interval of ten days. Again, in all age-groups, not only was the 50% incidence
      dose for mucosa desquamation similar, but also the full biphasic course of
      radiation reactions. These data therefore demonstrate that the capacity of the
      lip mucosa basal cells to restore the radiation damage was not modified by the
      phenomenon of aging.

PMID- 1992543
TI  - Survival after groin dissection for malignant melanoma.
AB  - Groin dissection was performed in 158 patients with malignant melanoma
      (superficial dissection, 76 patients; radical dissection, 82 patients). Of 63
      patients with palpable nodes, 57 patients (90%) had histologic involvement. Of 93
      patients with nonpalpable nodes, 31 patients (33%) had histologically positive
      nodes. The 5-year survival rate for patients with histologically negative nodes
      (n = 69) was 77%; the 5-year survival rate for patients with histologically
      positive nodes (n = 89) was 43%. The respective 5-year disease-free survival
      rates were 72% and 34%. Of 57 patients with palpable, positive inguinal nodes, 21
      patients (37%) had involvement of the deep nodes. Of 31 patients with
      nonpalpable, histologic involvement of the inguinal nodes, six patients (19%) had
      or developed involvement of the deep nodes. One of two patients with uncertain
      clinical status of the nodes preoperatively had positive deep nodes. In
      prophylactic node dissection, frozen section of the inguinal group of the nodes
      does not provide a reliable method, because of sampling errors, in determining
      microscopic involvement of the nodes and in deciding whether a superficial or
      radical groin dissection is to be done. For patients with positive nodes the 5
      year survival rate was 48% when only the inguinal group was involved and was 28%
      when both inguinal and deep nodes were involved; the respective 5-year disease
      free survival rates were 39% and 20%. Survival after therapeutic groin dissection
      may partly depend on the thoroughness of the procedure. Patients who have
      positive, deep nodes and who are undergoing an incontinuity dissection of the
      inguinal, iliac, and obturator nodes have an appreciable 5-year survival rate.

PMID- 1992544
TI  - The role of resection in the management of melanoma metastatic to the adrenal
      gland.
AB  - Melanoma metastatic to the adrenal gland diagnosed before death was exceedingly
      rare before the development of computed tomographic (CT) scanning. The records of
      28 patients with melanoma metastatic to the adrenal gland seen since 1975 were
      reviewed. Eighteen patients were men and 10 were women. Twenty-three patients had
      unilateral disease. Four patients were diagnosed only at autopsy, leaving 24 for
      analysis of treatment and survival. Twenty-one patients had received specific
      active immunotherapy, four had received chemotherapy (dacarbazine, lomustin,
      bleomycin, and vincristine), and three had received both before the diagnosis of
      their adrenal disease. Adrenal metastases were diagnosed by CT scanning in 14
      patients with symptoms, 10 (91%) of whom had pain. Ten patients were diagnosed by
      CT before entry into a chemotherapy protocol. Of eight patients who underwent
      resection of all known disease, five underwent unilateral adrenalectomy, two
      underwent unilateral adrenalectomy and bowel resection, and one underwent
      bilateral adrenalectomy. Two patients underwent partial resection of large
      unilateral tumors. Fourteen patients with adrenal metastases and disease
      elsewhere were initiated or continued with chemotherapy or were treated
      symptomatically. Mean survival in the group that underwent resection for cure was
      59 months (3 to 112 months), whereas survival in the group with unresectable
      tumors was 15 months (1.5 to 132 months). Four of eight patients who underwent
      resection for cure lived more than 5 years after detection of adrenal metastasis,
      whereas in only one of 14 patients with unresectable tumors was the same true.
      Patients with metastatic melanoma localized to one or both adrenal glands may
      benefit from early detection and surgical intervention.

PMID- 1992545
TI  - Evaluation of preoperative computed tomography in gastric malignancy.
AB  - Ninety patients with gastric malignancy underwent computed tomography (CT) before
      surgery. The CT findings regarding neoplastic invasion of adjacent organs and
      metastasis or enlarged lymph nodes were compared with the findings at laparotomy
      (85 cases) or autopsy (5 cases), thus permitting evaluation of the diagnostic
      accuracy of CT and its usefulness for predicting resectability. When present,
      neoplastic invasion of adjacent organs was overestimated or underestimated by CT
      in 21 cases. Invasion of adjacent organs according to CT was false positive in 17
      cases and false negative in 11 cases. When liver metastasis or enlarged regional
      or distant lymph nodes were present, CT overestimated or underestimated their
      extent in 17 cases, and the diagnosis was false positive in one case and false
      negative in 33 cases. The positive and negative predictive values of CT
      concerning resectability of the tumor were 81% and 64%, respectively. Routine
      preoperative CT in gastric malignancy is concluded to be of limited value and
      surgical exploration, when feasible, remains the method of choice.

PMID- 1992546
TI  - Total gastrectomy for gastric cancer in the elderly.
AB  - Of 1070 patients with gastric cancers, 292 patients underwent total gastrectomy
      during 13 years. Sixty patients were more than 70 years of age and 232 were under
      69 years. The incidence of well-differentiated carcinomas and poorly
      differentiated carcinomas was the same in the elderly patients, whereas the
      latter was dominant in the young patients. However, there was no significant
      difference between the two groups regarding location, size, macroscopic patterns,
      extent of lymph metastases, or stage classification. The rates of preoperative
      surgical risk factors were significantly different between the two groups (p less
      than 0.01): 90.0% for the elderly and 34.9% for the young patients. However, the
      rates of postoperative morbidity and mortality were 31.7% and 3.3% for the
      elderly and 24.1% and 1.3% for the young patients, respectively, with no
      significant difference. The 5- and 10-year survival rates after curative total
      gastrectomy were 48.6% and 23.2% for the elderly compared with 49.4% and 33.6%
      for the young patients, respectively, with no significant difference. A 5-year
      survival rate after noncurative operation was 0% for the elderly and 6.4% for the
      young patients. These results indicate that, when performed for cure, total
      gastrectomy with systematic lymphadenectomy can provide good long-term results
      for elderly, as well as young, patients.

PMID- 1992547
TI  - Abdominal aneurysms in childhood: report of a case and review of the literature.
AB  - Abdominal aneurysms are rare in children and are usually found in association
      with congenital cardiac or aortic malformations, connective tissue disorders,
      trauma, or previous arterial catheter placement. A 4-year-old girl who had a
      common iliac artery aneurysm, who had no history of arterial catheter placement
      or trauma, and who had no evidence of Marfan's or Ehlers-Danlos syndrome,
      arteritis, coarctation of the aorta, or other diseases associated with childhood
      aneurysms is presented. Resection of the aneurysm and arterial reconstruction
      were performed without the use of prosthetic material or vein graft. Pathologic
      examination showed no evidence of inflammation or medial degeneration in any of
      the layers of the arterial wall. This is the fourth report found in the
      literature of documented idiopathic abdominal aneurysm in a child. The conditions
      associated with abdominal aneurysms in childhood are discussed, and the
      literature is reviewed.

PMID- 1992548
TI  - Evidence for role of prostacyclin as a systemic hormone in portal hypertension.
AB  - The possibility that prostacyclin could be a systemic hormone and could mediate
      the splanchnic hyperemia of chronic portal hypertension was evaluated in rabbits
      in a normotensive state and in rabbits with chronic partial ligation of the
      portal vein. In rabbits with portal hypertension (PHT), 6-keto-prostaglandin F1
      alpha (PGF1 alpha, a prostacyclin degradation product) was elevated twofold in
      all vascular beds (systemic arterial, systemic venous, and portal venous) when
      compared with levels in control animals. In PHT rabbits, exogenous prostacyclin
      infusion after cyclooxygenase blockade through the systemic arterial, systemic
      venous, or portal venous route resulted in an equal elevation of 6-keto-PGF1
      alpha in the reciprocal vascular beds and restored the original precyclooxygenase
      blockade hemodynamics. These hemodynamic changes were of equal magnitude
      irrespective of site of infusion in PHT. In controls there was no significant
      change in 6-keto-PGF1 alpha or hemodynamics with intraportal infusion. We
      conclude that prostacyclin achieves systemic levels by escaping hepatic
      degradation resulting from portosystemic shunting in the animal with chronic
      portal hypertension.

PMID- 1992549
TI  - Increased sensitivity to endotoxemia by tissue necrosis.
AB  - In this study the interaction of endotoxemia and ischemic organ injury was
      investigated in a rat model. Animals received lipopolysaccharide to induce
      endotoxemia and were simultaneously subjected to renal ischemia. If only renal
      ischemia was induced, moderate azotemia occurred and all animals survived.
      Lipopolysaccharide treatment caused neither renal failure nor death. However,
      rats with both endotoxemia and renal ischemia showed severe azotemia, and 50% of
      the animals died within 48 hours. The observed mortality rate is unlikely related
      to renal failure since animals subjected to bilateral nephrectomy did not die
      within 48 hours after treatment with lipopolysaccharide. To further exclude the
      role of renal failure in the enhanced effect of endotoxemia, experiments were
      performed in which ischemic kidneys were excised from littermates and were placed
      in the abdomens of lipopolysaccharide-treated animals. A similar effect was
      observed: 50% of the animals died within 48 hours. Azotemia did not occur. Since
      tumor necrosis factor (TNF) is an important cytokine involved in endotoxemia
      induced morbidity and death, we studied the role of TNF in our model. Plasma
      levels of TNF were increased during endotoxemia. Concomitant renal ischemic
      injury did not influence the concentration of TNF. When animals were treated with
      recombinant TNF and were subsequently subjected to renal ischemic injury, again a
      50% mortality was observed, a rate similar to that in lipopolysaccharide-treated
      animals. We conclude that the sensitivity to endotoxemia is enhanced by tissue
      necrosis and may lead to death in the experimental model used in this study.

PMID- 1992550
TI  - A preliminary study of dye-enhanced laser photosclerosis.
AB  - Laser ablation of veins after injection of wavelength-specific dyes to enhance
      and localize energy absorption could provide a useful adjunct to current
      treatment options. To enhance the absorption of diode laser energy at 808 nm, ear
      veins of 41 rabbits were infused with 2 to 3 ml of indocyanine green dye (maximum
      absorption, 805 nm) and exposed for 2 to 20 seconds. Animals were killed between
      0 and 28 days after operation. Discrete time intervals of laser exposure exist
      during which various-sized vessels can be ablated without significant thermal
      injury to the overlying tissue. Small vessels (0.2 mm in diameter) blanch after 2
      to 3 seconds of exposure, whereas medium-sized vessels (2 mm in diameter) require
      8 to 10 seconds. Vessels can be ablated with a power density as low as 11.1
      W/cm2. Specimens taken immediately after laser exposure show vessel wall thinning
      and a reirradiation effect, created as laser energy initially absorbed by dye is
      reemitted. By the seventh day after operation, a brisk inflammatory response and
      acanthosis of the overlying epidermal layer develop. The lumen is partially
      filled by thrombus with cellular invasion. By postoperative day 28, the epidermal
      thickening and inflammatory reaction have resolved; the vessel walls are
      fibrotic. The use of low-power, air-cooled diode lasers, in conjunction with
      wavelength-specific dyes, may provide a simple, viable, and cosmetically
      appealing alternative to the treatment of superficial varicosities of the
      extremities.

PMID- 1992551
TI  - Effect of 3-hydroxybutyrate on posttraumatic metabolism in man.
AB  - Of 20 patients suffering trauma, with Injury Severity Scores greater than 20, 11
      patients received DL-3-hydroxybutyrate (3-OHB) at a rate of 25 mumol/kg/min for 3
      hours. The remaining nine patients received sodium DL-lactate at the same rate as
      the control subjects. With increased arterial concentrations of ketone bodies,
      the femoral arteriovenous difference (arterial concentration minus venous
      concentration) of ketone bodies increased proportionally in the 3-OHB group (R =
      0.853, p less than 0.001). Venous concentrations of nonesterified free fatty
      acids, alanine, glycine, and valine were decreased significantly in the 3-OHB
      group as compared to the control group. The concentration difference between
      femoral vein and artery (venous concentration minus arterial concentration) for
      these substrates also decreased, indicating decreased release from the extremity.
      A decrease in venous concentration of alanine and difference between femoral vein
      and artery reached 102.3 +/- 69.3 mumol/L and 32.6 +/- 22.8 mumol/L (mean +/-
      SD), respectively, after 3-OHB infusion. Decreased alanine release from muscle
      during 3-OHB infusion in traumatized patients suggests a suppressive effect of
      ketone body on posttraumatic protein catabolism.

PMID- 1992552
TI  - Hepatomuscular failure in septic catabolism: altered muscular response to plasma
      proteolytic factor in decreased hepatic mitochondrial redox potential.
AB  - To estimate the contribution of muscle protein in whole-body protein catabolism,
      the muscular contribution index (MCI; urine 3-methylhistidine/urine total
      nitrogen) was determined in 49 cases of elective laparotomy, together with the
      arterial blood ketone body ratio (KBR; acetoacetate/beta-hydroxybutyrate), which
      reflects hepatic mitochondrial redox potential. MCI increased after operation and
      the occurrence of severe infection, provided KBR was maintained above 0.7. In
      patients with sepsis, however, MCI decreased dependently with KBR (n = 33; p less
      than 0.01). In these patients, plasma proteolysis-inducing activity determined by
      in vitro bioassay increased in inverse proportion to KBR (n = 20, p less than
      0.01). Moreover, plasma concentrations of not only aromatic but also branched
      chain amino acids markedly increased when KBR decreased to below 0.4 (n = 23; p
      less than 0.05). Thus the role of muscle protein in septic catabolism is
      diminished under reduced hepatic mitochondrial redox potential, despite the rapid
      increase of proteolysis-inducing activity. This finally leads to the failure of
      amino acid uptake by muscles, as well as liver. These results suggest that the
      deteriorated substrate exchange may form the metabolic background for multiple
      systems organ failure, which is often preceded by reduced KBR.

PMID- 1992554
TI  - Treatment of solitary arteriovenous fistulas.
AB  - Four patients with a solitary arteriovenous fistula were treated by transvascular
      balloon embolization technique, which resulted in complete fistula closure in
      three patients and partial closure in one. There were two vertebral arteriovenous
      fistulas, one peroneal arteriovenous fistula, and one radial arteriovenous
      fistula. The first two fistulas were spontaneous, the other two were traumatic.
      The only partial occlusion of the peroneal fistula was, in our opinion, due to a
      technical failure, the balloon was inflated slightly proximal to the fistular
      orificium instead of in the orificium itself. There were no complications, and
      there was no morbidity. In our opinion transvascular balloon embolization
      technique is the treatment of choice for solitary arteriovenous fistulas.

PMID- 1992553
TI  - Use of a composite skin graft composed of cultured human keratinocytes and
      fibroblasts and a collagen-GAG matrix to cover full-thickness wounds on athymic
      mice.
AB  - In patients with extensive full-thickness burns, wound coverage may be
      accelerated if skin can be expanded to produce a skin replacement that
      reproducibly supplies blood to the wound and has good structural qualities. In
      addition, development of skin replacements may benefit patients who require
      reconstruction or replacement of large areas of abnormal skin. We have developed
      a composite skin replacement composed of cultured human keratinocytes (HK) and
      fibroblasts. Cultured human fibroblasts are seeded into the interstices, and
      cultured HKs are applied to the surface of a matrix composed of type I collagen
      crosslinked with a glycosaminoglycan, which has a defined physical structure.
      After HKs reach confluence on the matrix surface, the composite grafts are placed
      on full-thickness wounds on the dorsum of athymic mice. Graft acceptance,
      confirmed by positive staining with antibodies specific for human HLA-ABC
      antigens on HKs, is approximately 90%. A defined skin structure is present
      histologically by day 10 after grafting, with a differentiated epithelium and a
      subepidermal layer densely populated by fibroblasts and capillaries without
      evidence of inflammation. Fluorescent light microscopy to identify laminin and
      type IV collagen and electron microscopy confirm the presence of basement
      membrane components by 10 days after grafting. Attachment of the graft to the
      wound is similar with and without the addition of human basic fibroblast growth
      factor, a potent angiogenic agent, to the skin replacement before graft placement
      on wounds.

PMID- 1992555
TI  - Conservative management of penetrating vascular wounds.

PMID- 1992556
TI  - Antirejection effect of hepatotrophic factors.

PMID- 1992557
TI  - Greenfield filter placement.

PMID- 1992558
TI  - Appalled by incidence of transfusion.

PMID- 1992559
TI  - Toxicology of methacrylonitrile.
AB  - The chemistry, industrial usage, general toxicity and experimental use of
      methacrylonitrile are briefly reviewed. Methacrylonitrile, a reactive,
      unsaturated and methylated aliphatic nitrile, has industrial applications in a
      variety of organic processes related to the polymer industry. Its general toxic
      effects are primarily related to the release of cyanide and formation of reactive
      metabolites containing a double bond between carbon 2 and 3. Methacrylonitrile
      has been given by a variety of routes to mammalian species to study its toxic
      effects. More recent in vivo and in vitro experimental work concerning its
      toxicity and metabolism are summarized and possible mechanisms of this chemical's
      toxic action are discussed.

PMID- 1992560
TI  - Effects of amiodarone administration during pregnancy in Fischer 344 rats.
AB  - Amiodarone is a class III anti-arrhythmic compound that is iodinated, cationic
      and amphiphilic in nature. The clinical use of amiodarone may be associated with
      various side-effects, including pulmonary and hepatic toxicity. Use of this
      compound during pregnancy may therefore place the fetus at risk through in utero
      exposure. This study was designed to observe any gross developmental effects that
      may be caused by the administration of amiodarone to Fischer 344 rats during
      pregnancy, investigate the placental transfer of amiodarone and its principal
      metabolite, desethylamiodarone and determine the levels of amiodarone and
      desethylamiodarone in the maternal and newborn lung, liver and plasma. To conduct
      this study, 35 mg/kg of amiodarone was administered daily to pregnant rats for
      either the last 7 days of pregnancy, the last 14 days of pregnancy, or for the
      full 22 days of pregnancy. Drug treatment had no effect on the length of
      gestation or litter size. Maternal weight gain was decreased only when amiodarone
      was administered during the last 7 days of gestation. The birthweights of the
      offspring were decreased, however, crown to rump length was unaffected. Both
      amiodarone and desethylamiodarone accumulated in the offspring through placental
      transfer. The levels of both compounds were greater in maternal and newborn lung
      when compared to maternal and newborn liver, respectively. The maternal lung and
      liver concentrations of both compounds were significantly higher than the
      respective newborn concentrations. The newborn plasma concentrations of
      amiodarone and desethylamiodarone were significantly lower than maternal levels
      indicating that the placenta may not be totally permeable to the two drugs.

PMID- 1992561
TI  - Pulmonary microsomal alterations following short-term low level inhalation of p
      xylene in rats.
AB  - Rats exposed to 300 ppm para-xylene vapor for 1, 3 or 5 days, 6 h/day, exhibited
      alterations in pulmonary microsomal membrane structural and metabolic parameters.
      Following 1 day of exposure, conjugated diene levels were elevated while total
      phospholipid levels, P-450 content, benzyloxyresorufin O-dealkylase activity and
      2-aminofluorene N-hydroxylase activity were decreased. Core and leaflet membrane
      fluidity, ethoxyresorufin O-deethylase activity and aryl hydrocarbon hydroxylase
      (AHH) activity were unchanged at this time. Altered parameters began to return to
      control values by day 3 of exposure except for 2-aminofluorene N-hydroxylase
      activity, which remained decreased throughout the time course, and core membrane
      fluidity which was increased following 3 days of exposure. After 5 days of
      exposure, all parameters returned to control levels with the exception of AHH
      activity which was increased 41% at this time. Extracellular surfactant levels
      were also decreased by 1 and 3 days of exposure but returned to control values
      after 5 days. Initial pulmonary alterations produced by low level p-xylene
      exposure may be mediated by a peroxidative process. The initial damage triggers
      an adaptive response in lung tissue which possibly involves enzyme induction
      and/or cell proliferation. The increase in AHH activity after 5 days of exposure
      could have important consequences on the metabolism of co-administered
      xenobiotics.

PMID- 1992562
TI  - Validation of a non-invasive technique to assess development of airway
      hyperreactivity in an animal model of immunologic pulmonary hypersensitivity.
AB  - Airway hyperreactivity (AHR) is considered to be a prominent and consistent
      feature of the asthmatic. Accordingly, in developing animal models of asthma, it
      is important to have methodologies available for repeated assessment of airway
      reactivity (AR). We have described a methodology to assess AR in conscious
      minimally restrained guinea pigs, AR being quantified as the airborne
      concentration of histamine (mg m-3) necessary to produce a mild airway
      constriction. The present study sought to validate that methodology by assessing
      its ability to detect changes in AR associated with immediate-onset pulmonary
      hypersensitivity responses. Guinea pigs were sensitized by intraperitoneal
      injection of ovalbumin (OA) and challenged with OA aerosol 3 weeks later. All
      animals developed severe immediate-onset airway constrictive responses. AR was
      assessed 1 h later, upon return to normal breathing patterns. Hyperreactivity was
      apparent from response to 0.50 mg m-3 histamine when compared with 2.10 mg m-3
      histamine needed for baseline response. In control, sham sensitized animals AR
      remained at 2.12 mg m-3 after OA inhalation challenge. The results demonstrate
      the ability of this methodology to detect airway hyperreactivity to histamine
      resulting from a pulmonary hypersensitivity response. By requiring neither
      surgery nor any invasive procedure, the technique is appropriate for serial
      measurements of AR as is needed in development of an animal model for asthma, a
      chronic airway disease.

PMID- 1992563
TI  - Dose-response relationship between urinary cadmium and metallothionein in a
      Japanese population environmentally exposed to cadmium.
AB  - The dose-response relationship between cadmium (Cd) exposure and renal
      dysfunction, as measured by urinary Cd and metallothoinein (MT), was evaluated in
      a population living in the Kakehashi River basin, a Cd-polluted area in Japan.
      Morning urine specimens were collected from 1397 men and 1713 women who were 50
      years or older. In addition, urine specimens were collected from a control
      population consisting of 110 men and 130 women. The 97.5% upper limits for MT in
      the control population were used to determine the prevalence rates for MT-uria at
      various urinary Cd concentrations. Probit linear regression analysis showed
      significant dose-response relationships between MT and Cd. In the control
      population, prevalence rates of MT-uria for men and women were 1.8 and 3.1%,
      respectively. Based on the prevalence rates of MT-uria in the control population,
      the upper limits for the urinary Cd concentrations were calculated from the
      slopes of the regression lines to be 4.2 and 4.8 micrograms/g creatinine for men
      and women, respectively. These values, which are similar to those reported
      previously using urinary beta 2-microglobulin as the indicator, may be of use in
      establishing the biological threshold, i.e. maximum allowable concentration, for
      urinary Cd in the environmentally exposed Japanese population.

PMID- 1992564
TI  - Combined lead acetate and disulfiram treatment-induced alterations of glial
      fibrillary acidic protein (GFA) immunoreactive astrocytes in brain smears.
AB  - Dithiocarbamates are known to form lipid-soluble complexes with lead and greatly
      increase brain lead levels. The present study was undertaken to investigate
      whether lead acetate, when administered together with disulfiram (Antabuse,
      metabolite of dithiocarbamate) during development, would induce morphological
      changes in brain astrocytes. Female Sprague-Dawley rats were given 0.25% lead
      acetate in the drinking water from day one of pregnancy and this treatment was
      continued after birth until the litters were 4 weeks old. In addition, some dams
      received disulfiram in a dose of 0.1 mmol/kg p.o. twice weekly and after
      parturition this dose was given s.c. directly to the offspring twice a week. Lead
      acetate and disulfiram treatments were discontinued at weaning and animals
      sacrificed 3 weeks later. Samples of parietal cortex, hippocampal formation and
      cerebellar cortex were dissected out and smeared onto glass-slides and astrocytes
      were visualized in toto using immunohistochemistry with antibodies against glial
      fibrillary acid protein (GFA), enabling morphometric analysis with a computerized
      image analyser. Animals treated with lead acetate showed a minor increase in the
      size of the GFA-immunoreactive astrocytes in parietal cortex smears, while
      animals treated with disulfiram showed no difference in size or form compared to
      controls. However, in combined lead acetate and disulfiram-treated animals a
      profound increase in astrocyte size and an increase in the number of processes of
      the individual GFA-immunoreactive astrocytes could be demonstrated in parietal
      cortex. No significant changes were noted in GFA-immunoreactive astrocytes of
      hippocampal smears following the different treatments, while GFA-immunoreactive
      astrocytes in cerebellar cortex smears were significantly smaller and had reduced
      number or processes following the combined lead acetate and disulfiram treatment
      compared to lead acetate treatment or controls. It is concluded that combined
      exposure to lead acetate and disulfiram during development induces regionally
      specific changes in GFA-immunoreactive astrocyte morphology. Furthermore, the
      present study demonstrates the usefulness of smear preparations combined with
      computerized image analysis to study the morphology of GFA-immunoreactive
      astrocytes as an index of toxic effects in CNS.

PMID- 1992565
TI  - Advanced prostatic carcinoma. Surgical craft: partial and total penectomy for
      cancer.

PMID- 1992567
TI  - Use of intravenous stilbestrol diphosphate in patients with prostatic carcinoma
      refractory to conventional hormonal manipulation.
AB  - The patient presenting with severe bone pain after primary hormonal therapy, with
      vertebral collapse, or with uremia resulting from ureteric obstruction should be
      considered for intravenous stilbestrol diphosphate therapy. The urologist can
      expect early marked improvement in the patients' mobility and pain, with a
      reduction in analgesic requirements, from a single 7-day course of treatment. In
      addition, the drug is inexpensive and free of the side effects commonly
      associated with cytotoxic therapy. Accurate monitoring of the response is
      possible with serum prostate-specific antigen measurements, which also enable
      further therapy to be planned efficiently.

PMID- 1992566
TI  - Use of suramin in treatment of prostatic carcinoma refractory to conventional
      hormonal manipulation.
AB  - Suramin and related compounds, in view of their growth factor and enzyme binding
      properties, represent in many respects a novel approach to the treatment of
      cancer. Although in this preliminary analysis of suramin use in the treatment of
      metastatic prostate cancer, the objective response rate does not appear
      impressive, much work still needs to be done to optimize suramin's administration
      to patients and to elucidate its various postulated mechanisms of action. The
      development of related compounds with more specific enzyme and growth factor
      antagonist properties is under way.

PMID- 1992568
TI  - Management of spinal cord compression secondary to metastatic prostatic
      carcinoma.
AB  - Spinal cord or cauda equina compression from prostatic cancer is an oncologic
      emergency necessitating prompt evaluation and treatment. The strong correlation
      between pretreatment motor status and treatment outcome underscores the
      importance of immediate treatment before further neurologic deterioration and
      before the damage to the spinal cord becomes permanent. Patients with known
      osseous metastases should be alerted by their clinicians to seek medical help
      within hours should they develop weakness in an extremity. Prompt MRI of the
      entire spine should be done prior to treatment. Myelography should be reserved
      for those patients who cannot undergo a technically adequate or expeditious MRI
      study. The convenience of MRI relative to myelography allows clinicians to
      diagnose actual or impending spinal cord compression earlier. High-dose steroids
      (dexamethasone) should be instituted immediately, and endocrine therapy should be
      started if not already in use. Ambulatory and moderately paraparetic patients
      seem best treated initially with radiation alone. Immediate surgical
      decompression should be used in patients with an expected lifespan of at least 6
      months who deteriorate during radiation, who have had previous radiation to the
      involved site, or who have a potentially correctable unstable spine. In addition,
      paraplegic patients or severely paraparetic patients with recent neurologic
      deterioration should be treated with immediate surgical decompression if they are
      judged reasonably able to tolerate the surgery. These patients should then
      receive postoperative radiation treatment.

PMID- 1992570
TI  - Treatment of metastatic prostate cancer of the spine.
AB  - There is a wide spectrum of presentations for prostate cancer metastatic to the
      spine. Important factors are the patient's age and general health; the extent and
      location of spinal involvement; the patient's neurologic status and degree of
      pain; the relative contribution of a blastic or lytic response; and the
      experience and training of the spinal surgeon, medical oncologist, and radiation
      oncologist. The spine is both a weight-bearing structure and a housing for the
      spinal cord, and failure to consider both functions may lead to unsatisfactory
      treatment results. Treatment options include hormonal therapy, inhibitors of bone
      metabolism, glucocorticoid therapy, radiotherapy, halo-vest, surgical
      debridement, decompression and stabilization, and appropriate pain management and
      support. One must not lose sight of the fact that the goals are palliation and
      that ultimate demise is unavoidable in patients with metastatic prostate cancer.

PMID- 1992569
TI  - Advanced prostatic carcinoma. Early versus late endocrine therapy.
AB  - Since the landmark observations of Huggins and Hodges in 1941, androgen
      deprivation has been the mainstay of treatment for advanced-stage prostate
      cancer. Although early, poorly controlled studies suggested enhanced survival
      with hormonal therapy, this view fell into disfavor as a result of the
      observations of the first and second VACURG studies. Recently, there has been a
      proliferation of experimental and clinical data supporting early androgen
      deprivation, including a reanalysis of the VACURG data, which suggests a survival
      advantage for younger patients with stage D disease and high-grade tumors who
      undergo androgen-ablative therapy at the time of diagnosis. The risk-benefit
      analysis presented in this review is strongly supportive of early hormonal
      therapy. Finally, long-term survival of patients with metastatic prostate cancer
      will require the development of novel treatment strategies effective against
      androgen-resistant tumor cells and their use in concert with early androgen
      deprivation.

PMID- 1992572
TI  - Future developments of nonhormonal systemic therapy for prostatic carcinoma.
AB  - Prostate cancer is the most common type of cancer in men. Despite increased
      public awareness and new screening methods, a significant proportion of men
      continue to present with metastatic disease. Most men will respond initially to
      hormonal intervention; however, given time, the majority will have recurrences of
      hormonally unresponsive tumor on which present therapies have little impact.
      Research continues to identify new cellular and molecular aspects of prostate
      cancer with implications as possible sites of therapeutic intervention.

PMID- 1992571
TI  - Partial and total penectomy for cancer.
AB  - Squamous carcinoma of the penis remains an uncommon tumor in the United States.
      In the properly selected patient, partial or total penectomy performed with an
      understanding of the salient surgical anatomy results in adequate local control
      of these cancers with excellent functional and cosmetic results.

PMID- 1992573
TI  - Imaging of patients with stage D prostatic carcinoma.
AB  - In conclusion, it would appear from present evidence that several statements can
      be made. First, MRI is the most accurate method of staging the periprostatic
      spread of carcinoma. Both the prostate and the regional nodes can be evaluated.
      The role of ultrasound is, at present, unclear. Second, the utility of CT has
      diminished with the emergence of high-quality MRI, but in situations in which MRI
      scans are inconclusive (e.g., in the assessment of paraaortic node disease, in
      which images are degraded by peristaltic movement), CT may be useful. Third, the
      choice of method for the assessment of nodal disease is a more difficult
      question. Although MRI and CT have replaced lymphography in most centers, the
      latter study, especially when combined with fine-needle aspiration biopsy, still
      is useful. Fourth, bone metastases are best assessed with scintigraphy, which can
      point to areas requiring supplemental plain radiography. An MRI study of the
      spine, although highly sensitive, is not practical. Fifth, MRI is superior to CT
      myelography in assessing spinal disease. Finally, the chest radiograph is the
      mainstay of assessing chest involvement.

PMID- 1992574
TI  - Total androgen ablation: Canadian experience.
AB  - A multicenter randomized, double-blind trial comparing total androgen blockade
      obtained by the use of castration with a pure anti-androgen (nilutamide) with
      simple castration was begun. One hundred and five patients received the combined
      treatment and 103 the orchiectomy plus placebo. Several features were used to
      evaluate the efficacy. Bone pain responded better to combined treatment at 6
      months (P = 0.042). The number of favorable responses, as evaluated by the NPCP
      criteria, was 61% with simple castration and 78% with the combined treatment (P =
      0.013). There was no statistically significant difference between the two groups
      in time to progression (logrank test P = 0.462) or survival (logrank test P =
      0.137) despite an increase in median survival of 5.4 months. All other measures
      showed no difference between the two treatments. With total androgen blockade,
      50% of the patients had disease progression at 1 year, and 45% were dead at 2
      years. A review of the results of similar reported studies suggests no
      improvement or very modest improvement with total androgen blockade over
      testicular androgen ablation alone.

PMID- 1992575
TI  - Use of the nonsteroidal anti-androgen Casodex in advanced prostatic carcinoma.
AB  - Pure anti-androgens have advantages over steroidal anti-androgens of the
      cyproterone acetate type in the treatment of patients with advanced prostate
      cancer because they do not have steroidal side effects or such a marked
      inhibitory effect on libido. In addition, the long half-life of a pure anti
      androgen such as Casodex results in maintenance of high serum anti-androgen
      concentrations, which allays concern over the clinical significance of any small
      rise in serum testosterone concentrations. The anti-androgen of choice for the
      treatment of androgen-responsive diseases has yet to be defined. However, this
      choice should be based on extensive clinical evaluations of a drug as
      monotherapy. As always, the clinical efficacy and tolerability of the drug will
      be important factors in determining the anti-androgen of choice; however,
      favorable pharmacokinetics should be emphasized in the treatment of a disease in
      which high and sustained concentrations of antagonist must be present to prevent
      androgenic stimulation. Casodex, a pure anti-androgen with a relatively long half
      life, produces objective and subjective responses similar to those of surgical or
      pharmacologic castration and is well tolerated. Its profile makes it a strong
      candidate for consideration as the future anti-androgen of choice in the
      treatment of advanced prostate cancer.

PMID- 1992576
TI  - Initial results with slightly modified Kock pouch.
AB  - My initial experience with 20 patients undergoing Kock pouch continent urinary
      diversion is reviewed. The procedure has been slightly modified from that
      described by Kock and Skinner. All patients have been followed for at least four
      months (median, 33 months). There have been no early complications related to the
      pouch. The most significant problem, incontinence, has occurred in 2 patients
      (10%) at three and four months, respectively, after surgery. Only 1 of these
      patients required temporary use of an external appliance. Leakage was due, in
      both cases, to a patulous efferent nipple valve. Both were repaired by plication
      of the nipple, and no new efferent limbs were constructed. In 1 patient (5%)
      prolapse of the afferent limb associated with reflux and pyelonephritis developed
      one year post-surgery. Stones have developed in 3 patients (15%). All patients
      are currently continent and stone-free, and all are pleased with the result.

PMID- 1992578
TI  - Use of standard contraceptive diaphragm in management of stress urinary
      incontinence.
AB  - The management of stress urinary incontinence (SUI) consists of either surgical
      intervention and/or pharmacologic manipulation. Twelve patients with SUI were
      evaluated for management by the use of a fitted standard contraceptive diaphragm.
      Complete resolution of SUI was achieved in 11 of 12 patients (91%). Two of the 12
      patients achieved continence but withdrew from the study because of associated
      discomfort from the diaphragm, therefore, complete resolution of SUI was achieved
      in 9 of 12 patients (75%).

PMID- 1992577
TI  - Carcinoma of female urethra. Manitoba experience: 1958-1987.
AB  - Fourteen female patients with primary urethral carcinoma were treated at the
      Manitoba Cancer Foundation in the last twenty-nine years. The relationship of
      natural history to the stage, location, and therapeutic modality has been
      reviewed. A higher stage and length of urethral involvement affected prognosis
      negatively, whereas lower stage had a positive prognostic effect and location of
      tumor had no prognostic influence. Two patients with Stage C, who failed to
      received inguinal node radiotherapy, died of disease recurring in the inguinal
      area. Patients who received inguinal radiation (3 patients Stages B, C, and D1)
      had no regional recurrence. It is suggested that, for all female urethral
      carcinoma, bilateral ilioinguinal nodes be included in the radiation field. For
      radical treatment, iridium 192 insertion in combination with external beam
      treatment is recommended.

PMID- 1992579
TI  - Dilated renal collecting systems: differentiating obstructive from nonobstructive
      dilation using duplex Doppler ultrasound.
AB  - Two patients with ileal loop urinary diversions, studied with real-time and
      Doppler sonography ("duplex sonography") of the kidneys, were shown to have
      dilated intrarenal collecting systems. Resistive index measurements calculated
      from the Doppler signal correctly identified obstructive dilatation in 1 case and
      nonobstructive dilatation in the other.

PMID- 1992580
TI  - A middle-aged man with dysuria and weight loss.

PMID- 1992581
TI  - Techniques in endoscopic lithotripsy using pulsed dye laser.
AB  - The pulsed dye laser represents a new tool in the treatment of ureteral calculi.
      Laser energy channeled through a delicate optical fiber is used to disimpact and
      fragment calculi. Standard ureteroscopic instruments including graspers, baskets
      and dilatation balloons can be used with the laser system. Interchangeable
      optical fibers ranging from 200 to 400 micrometers deliver up to 120 mJ of energy
      to the stone's surface. For two weeks in 1989 an endourology clinic was held in
      upper Egypt. Eighty patients ranging in age from nine years to sixty-seven years
      old were evaluated and treated endoscopically. Endoscopes ranging from 6.9F to
      12.5F were used to deliver the optical fiber. All stones visualized
      endoscopically were fragmented. Greater than 60 percent of the stones fragmented
      were composed of pure calcium oxalate monohydrate. Schistosoma hematobium was
      endemic among our study group. Bilharzial strictures of the distal ureter were
      noted in 30 percent of these patients. Treatment of these strictures using both
      balloon dilatation and graduated Teflon dilators is reviewed. Techniques in
      treating different types of ureteral calculi were explored. Large calcium oxalate
      dihydrate stones were treated most efficiently with the 3-point fragmentation
      technique. The shear off-center technique was used for the calcium oxalate
      monohydrate calculi. Variations in total energy delivered and frequency of
      pulsation allowed for prompt stone disimpaction as well as prevention of
      retrograde fragment migration. Concurrent use of stone baskets and graspers with
      the pulsed dye laser was explored.

PMID- 1992582
TI  - Bilateral renal cell carcinoma with metastasis to thyroid.
AB  - A case of bilateral synchronous renal cell carcinomas with metastases to the
      regional lymph nodes and later to the thyroid gland was treated with aggressive
      surgical extirpation and adjuvant gamma interferon. The patient continues to have
      an excellent performance status sixteen months after initial diagnosis despite a
      large tumor burden at presentation.

PMID- 1992583
TI  - Pulmonary embolization of iodine-125 seeds following prostate implantation.
AB  - The optimal treatment of prostatic carcinoma limited to the gland remains
      controversial. Treatment has included implantation of Iodine-125 seeds via both a
      suprapubic approach and, more recently, a transperineal technique utilizing
      ultrasound guidance. We recently have noted a heretofore unreported complication
      with this latter technique, namely, embolization of seeds to the lungs. Review of
      the chest x-ray films of 31 patients who underwent suprapubic implants showed no
      evidence of this phenomenon. One of 5 patients undergoing transperineal implant
      was found to have seeds lodged in the lung. Complications surrounding the various
      treatments of localized prostate carcinoma are reviewed.

PMID- 1992584
TI  - Flow cytometric detection of tumor metastases during urologic surgery.
AB  - Flow cytometric studies were performed on peripheral blood obtained before,
      during, and subsequent to urologic surgery. The results suggest that 7 of 11
      patients had a brief period during surgical manipulation when they had cells from
      the primary surgical site in the peripheral blood. Concentration of such cells
      was generally less than 10(2)/mL even during the intraoperative period. These
      findings suggest that perioperative tumor seeding is a real concern, and that
      flow cytometry can be used to study maneuvers to reduce its incidence.

PMID- 1992585
TI  - Mobile epididymis. A new clinicopathologic entity in genesis of male infertility
      and its treatment by epididymopexy.
AB  - Mobile epididymis plays an important role in the genesis of male infertility. It
      constituted 9 percent of a consecutive series of idiopathic infertility. Of 200
      patients examined (100 fertile and 100 infertile), mobile epididymis was detected
      in 9 infertile patients. The clinical picture is characteristic. Epididymis is
      widely separated from testicle and moves freely from side to side. Its body and
      tail are ill formed and the epididymovasal angle is obtuse. Azoospermia was
      persistent in 3 patients and intermittent in 6 patients. Testicular biopsy showed
      tubular dilatation. Epididymopexy was performed in the 9 patients to fix the
      epididymis to testicle: 3 patients showed improvement in semen quality with two
      resultant pregnancies. Failures were due to advanced testicular damage.
      Infertility in mobile epididymis appears to result from obstruction of efferent
      ductules, testicular ischemia, and/or interference with sperm maturation,
      transport, or delivery.

PMID- 1992586
TI  - Simplified method for outpatient teaching of continent reservoir catheterization.

PMID- 1992587
TI  - Modified TURP loop for bladder neck incision.

PMID- 1992588
TI  - Microtip urethral pressure profile measurement in men.

PMID- 1992589
TI  - Fulguration of urethral condylomata: modified technique using visual urethrotome.

PMID- 1992590
TI  - Simple urodynamic evaluation of incontinent elderly female nursing home patients.
      A descriptive analysis.
AB  - We present a descriptive analysis of the functional, mental, and urodynamic
      status of a population of incontinent elderly female nursing home patients. One
      hundred fifty-five intermediate care female patients with a mean age of 85.5
      years were identified as being incontinent of urine at least once daily. After
      urologic evaluation, each patient was classified into one of four categories:
      incontinence with normal cystometrogram 68 (44%), detrusor instability (DI) 52
      (34%), stress incontinence (SI) 27 (17%), or overflow incontinence (OI) 7 (4%).
      Thirteen weeks later, patients were again studied using simple water cystometry.
      At follow-up evaluation, 45 patients (33%) had urodynamic findings which differed
      from the initial evaluation. Of these women, 10 with DI, 12 with SI, and 2 with
      OI were found to have normal cystometric parameters at the time of follow-up
      study, while 19 (14%) who initially had normal cystometric findings had evidence
      of DI (11) or SI (3). Strong correlation between urinary incontinence in patients
      with normal cystometric findings and moderate to severe cognitive impairment was
      present. Simple urodynamic evaluation did identify patients with SI and OI who
      might benefit from specific therapy. Urodynamic evaluation of incontinent elderly
      female nursing home patients is indicated and may provide direction for planning
      treatment strategies.

PMID- 1992591
TI  - Intravesical bacillus Calmette-Guerin for patients with high-risk superficial
      bladder cancer.
AB  - Intravesical bacillus Calmette-Guerin (BCG) was employed in the treatment of 55
      patients with aggressive superficial transitional cell carcinoma of the bladder
      (cTa, cT1, cTis). All of the patients had a previous history of recurrent
      superficial disease, and 41 (75%) were treatment failures following other
      intravesical therapy. Thirty-six (66%) patients responded to treatment, and 19
      (34%) were treatment failures. Twenty-seven (66%) of 41 patients with cTa-cT1
      tumors and 9 (64%) of 14 patients with cTis responded, with a mean follow-up
      period of 30.5 months. Disease progression was noted in 8 (15%) of the patients
      and muscle invasive disease in 6. Patients with a history of three or more
      previous events of tumor recurrence, positive urinary cytology, and multicentric
      disease, all fared worse than patients without these characteristics (p less than
      0.05). BCG is an effective agent in controlling superficial transitional cell
      carcinoma of the bladder, even in a high-risk group of patients who failed
      previous intravesical therapy. BCG should be employed in this group of patients
      prior to radical surgery.

PMID- 1992592
TI  - Possible implications of antisperm antibodies beyond infertility.

PMID- 1992593
TI  - Absent communication between the cavernous bodies.

PMID- 1992594
TI  - Cosmetic orchiectomy.

PMID- 1992595
TI  - Percutaneous urinary diversion in patients with hormone-refractory prostate
      cancer.
AB  - Twenty-two patients with hormone-refractory prostate cancer underwent
      percutaneous urinary diversion; at the time, all but one had metastatic disease.
      Eleven patients received postnephrostomy therapy. The median survival time for
      all the patients was one hundred nineteen days. Overall, 41 percent of the
      patients' remaining lifetime was spent in the hospital. Six never left the
      hospital and 10 required rehospitalization; the remaining 6 patients were never
      rehospitalized. The median survival time for this group of patients was shorter
      than the expected survival of similar patients without ureteral obstruction. It
      appears that percutaneous urinary diversion does not improve the quality of life
      of these patients.

PMID- 1992597
TI  - Anandron: a new step in the treatment of advanced prostate cancer. Proceedings of
      a symposium. June 12, 1989.

PMID- 1992596
TI  - Prognostic factors and value of adjunctive nephrectomy in patients with stage IV
      renal cell carcinoma.
AB  - We reviewed 57 cases of Stage IV renal cell carcinoma to clarify the factors
      influencing prognosis and to evaluate the value of nephrectomy. Cumulative
      survival from the initial diagnosis was analyzed with respect to the patients'
      age, sex, side of primary tumor, initial performance status (PS), site of
      metastasis, and nephrectomy. Overall survival for the patients was 51 percent at
      one year, 22 percent at three years, and 11 percent at five years. Age, sex, and
      side of primary tumor had no influence on survival. Improved survival was
      correlated with good PS, metastases limited to single organ, and removal of the
      primary tumor. With regard to histopathologic features in nephrectomized
      patients, low grade and stage were correlated with longer survival. These factors
      should be considered in the analysis of results of future clinical trials of
      metastatic renal cell carcinoma.

PMID- 1992598
TI  - Pharmacokinetics and metabolism of nilutamide.
AB  - Data are available on the pharmacokinetics and metabolism of nilutamide in the
      rat, dog, and human (normal volunteers and patients with advanced prostatic
      carcinoma). Studies using 14Carbon-nilutamide, radioimmunoassay, and high
      performance liquid chromatography (HPLC) are reviewed. In the rat,
      bioavailability by the oral route was complete. The majority of the plasma
      radioactivity was unchanged nilutamide up to six hours, t1/2 was seven hours, and
      clearance was 150 mL/hour/kg body weight. Metabolism studies identified 6 urinary
      metabolites. The major metabolites result from reduction of the nitro group
      initially to an hydroxylamine (17%) and then to a primary amino (26%) group. In
      normal volunteers the compound was rapidly absorbed, displayed linear kinetics
      over a dose range of 100-300 mg, and declined slowly in plasma with a terminal
      phase t1/2 of forty-three to forty-nine hours. In studies in 12 patients with
      advanced (Stage D) prostatic carcinoma, single-dose kinetics after 14C-nilutamide
      and kinetics with repetitive twice-daily dosing of two to seven weeks were
      measured. Terminal phase plasma t1/2 of unchanged nilutamide was 56 +/- 19 hours
      and of total radioactivity 87 +/- 27 hours (mean +/- SD). Area under the curve of
      plasma radioactivity was 23 to 38 percent unchanged nilutamide. Urinary excretion
      of radioactivity was slow and incomplete because the collection time was not long
      enough in regard to t1/2 (mean after 5 days, 62 +/- 10%) and consisted almost
      entirely of metabolites. Steady-state plasma levels of nilutamide were reached in
      about two weeks. It can be concluded that in humans, unlike other species, plasma
      decay of nilutamide is very slow. Elimination is almost exclusively by
      metabolism. Single-daily dosing is appropriate. Hepatic impairment could be
      expected to prolong plasma decay; renal impairment is likely to have little
      effect.

PMID- 1992599
TI  - Castration plus nilutamide vs castration plus placebo in advanced prostate
      cancer. A review.
AB  - Combination of antiandrogen treatment with surgical or medical castration should
      improve the efficacy of endocrine treatment of prostatic cancer by blocking the
      effects of adrenal androgens. A nonsteroidal antiandrogen, nilutamide, has shown
      promising results in preliminary open studies. In a short-term (29 days)
      comparison of nilutamide plus buserelin and buserelin plus placebo, nilutamide
      (300 mg/day), significantly reduced bone pain, and fewer patients experienced
      worsening pain than in the control group. The initial buserelin-induced increase
      in prostatic acid phosphatase was prevented by nilutamide, but there was a
      similar increase in testosterone and gonadotropin concentrations to that seen in
      the control group. Thus, nilutamide can prevent the tumor flare-up associated
      with the start of luteinizing hormone-releasing hormone (LH-RH) treatment, even
      though the endocrine responses are not affected. In three multicenter,
      randomized, double-blind placebo-controlled trials of castration and nilutamide
      involving 248 patients, the combination of nilutamide and castration decreased
      bone pain, improved performance status, and increased the number of patients with
      objective regression, compared with patients who were castrated but did not
      receive nilutamide. Nilutamide was generally well tolerated, though visual
      disorders, gastrointestinal disorders, and alcohol intolerance were reported in
      patients receiving nilutamide. The results suggest that nilutamide improves the
      efficacy of castration in patients with prostatic cancer. Current studies are
      investigating the effects of this treatment on survival and the risk-benefit
      ratio.

PMID- 1992601
TI  - Anandron: a new step in the treatment of advanced prostate cancer.

PMID- 1992600
TI  - Combination of Anandron with orchiectomy in treatment of metastatic prostate
      cancer. Results of a double-blind study.
AB  - A multicenter, randomized double-blind study was carried out in 203 patients with
      metastatic prostate cancer, in order to compare the efficacy of complete
      suppression of androgens achieved with surgical castration and nilutamide
      (Anandron), 100 mg t.i.d. The combined therapy was well-tolerated by patients,
      and they noted a better relief of bone pain after six months than those in the
      control group. There was a greater number of favorable responses in the combined
      treatment group. In addition, despite a similar median progression-free actuarial
      rate, the combined treatment (nilutamide plus orchiectomy) offered an improved
      survival time over orchiectomy alone.

PMID- 1992602
TI  - Pharmacology of antiandrogens and value of combining androgen suppression with
      antiandrogen therapy.
AB  - Antiandrogens are compounds able to block the effect of androgens directly on
      their target cells by inhibiting their binding to the androgen receptor (AR). Two
      chemical classes of antiandrogens are presently on the market or in clinical
      trials: steroids (cyproterone, megestrol acetates), and nonsteroids (flutamide,
      nilutamide). Steroid antiandrogens interact not only with AR but also with
      progestin and glucocorticoid receptors and thus give rise to progestin and
      glucocorticoid effects. By contrast, nonsteroid antiandrogens interact only with
      AR and are thus devoid of other hormonal or antihormonal activities. Nilutamide
      does not need to be transformed into an active metabolite, unlike flutamide, and
      interacts with dog, rat, and human prostate AR in vitro. Its kinetics lead to a
      prolonged interaction with AR in vivo after administration to rats. In prostate
      cancer treatment, it is necessary to combine an antiandrogen to surgical or
      chemical (estrogens, LH-RH agonists) castration to obtain a complete suppression
      of androgens. The antiandrogen will block specifically, at the target site, the
      trophic effect of adrenal androgens left intact by castration, and the secretion
      of which can only be suppressed by treatments (adrenalectomy, aminoglutethimide,
      ketoconazole) that also suppress corticoid synthesis. We have shown that
      nilutamide counteracts the trophic effect, on the prostate of castrated rats, of
      adrenal androgens administered continuously (minipumps) at circulating levels
      similar to those recorded in castrated men. Nilutamide will also impede the flare
      up effect of the testosterone increase induced by LH-RH agonists at the beginning
      of treatment. We have shown in the rat treated with buserelin that the increase
      in prostate weight observed during the initial days of treatment by the LH-RH
      agonist can be inhibited by a combined treatment with nilutamide. This combined
      treatment "nilutamide plus castration" has been tested in an experimental
      androgen-dependent cancer model, the Shionogi tumor. The administration of
      nilutamide to mice, castrated twenty-four hours before the inoculation of tumor
      cells, delayed the appearance of tumors and reduced their number. Finally, the
      absence of androgen effect and the antiandrogen activity of the product were also
      demonstrated in human tumor cells in culture (T-47 D cells) transfected with the
      MMTV androgen-dependent promoter coupled with the CAT reporter gene.

PMID- 1992603
TI  - Technical note: radiolucent operating room table extension to facilitate
      intraoperative angiography.

PMID- 1992604
TI  - The bottom line. Can portable blood glucose monitoring improve the outcomes of
      diabetic patients?

PMID- 1992605
TI  - A novel method for optimum biopsy specimen preservation for histochemical and
      immunohistochemical analysis.
AB  - A novel method has been developed for optimally processing biopsy specimens
      combining freeze-substitution with low-temperature plastic embedding.
      Immunohistochemistry and conventional histochemical stains were all readily
      performed on tissue displaying high-quality morphologic preservation. Labile
      antigens, especially lymphoid cell surface antigens, were well preserved. This
      new method avoids the need for tissue fixation and combines the superior
      morphologic preservation of fixed embedded tissue with the reactivity of cryostat
      sections. This method ensures that diagnostic information from even the smallest
      biopsy specimen is maximized because a wide range of phenotypic markers can be
      applied and evaluated in relation to high-quality morphologic preservation of
      tissue. Biopsy specimens are stored at room temperature without loss of tissue
      specific characteristics during storage.

PMID- 1992606
TI  - Cytologic identification of clinically occult proliferative breast disease in
      women with a family history of breast cancer.
AB  - A cytologic method for sampling the normal breast by fine-needle aspiration (FNA)
      was used to determine the frequency of clinically inapparent proliferative breast
      disease (PBD) in women with family histories of breast cancer. The authors
      attempted to obtain specimens from each quadrant of both breasts in 51 female
      first-degree relatives of breast cancer patients. The study group had no
      detectable masses by physical examination or mammography. Samples were prepared
      on membrane filters, Papanicolaou stained, and evaluated cytomorphologically.
      Three hundred seventy-eight of 408 (92.6%) possible quadrants were sampled;
      cellular material was obtained from 290 (76.7%) quadrants. PBD was identified in
      20 of the 51 women (39.2%). When epithelium was obtained, nuclear area,
      perimeter, and diameter were measured with the use of computerized image
      analysis. Nuclei in samples containing atypical hyperplasia showed significant
      differences in these parameters when compared with cells from samples containing
      normal epithelium or benign hyperplasia. The authors' findings indicate that FNA
      sampling and computerized image analysis are useful in the detection and
      characterization of clinically inapparent PBD.

PMID- 1992608
TI  - Papillary carcinoma of the thyroid with mucoepidermoid features.
AB  - The significance and differential diagnoses of signet-ring cells found in the
      fine-needle aspirate of metastatic mucoepidermoid carcinoma from the thyroid are
      reported and discussed. The primary tumor occurred in a 35-year-old man, who had
      a history of neck irradiation during his childhood. Despite postoperative
      treatment with 60 Gy external radiation and 1,200 mCi 131I, the patient has at
      present--12 years after the initial operation--progressive disease with local
      recurrence in the neck as well as lung metastases.

PMID- 1992607
TI  - Metastatic small cell tumor of bone with 'true' rosettes and glial fibrillary
      acidic protein positivity.
AB  - A 15-year-old black girl was admitted to St. Jude Children's Research Hospital
      with a lytic lesion involving the right fourth metacarpal bone with a solitary
      metastasis to the ipsilateral axillary lymph node. Histologic examination of both
      the primary lesion and metastasis revealed a primitive small round cell lesion.
      Abundant rosettes with central lumina were present in the metastasis.
      Immunohistochemical stains performed on sections of the metastasis were strongly
      positive for glial fibrillary acidic protein (GFAP) and negative for neuron
      specific enolase (NSE), S-100 protein, and Leu-7. Electron microscopic
      examination of the metastasis revealed lumen formation with apical microvilli and
      juxtaluminal junctional complexes. This tumor exhibits features that are
      suggestive, but not definitive, of primitive ependymal differentiation and
      further expands the morphologic and immunophenotypic range of small round cell
      tumors of bone.

PMID- 1992609
TI  - Follicular dendritic cells in Hodgkin's disease.
AB  - The distribution of follicular dendritic cells (FDCs) was studied in 66 lymph
      nodes affected by Hodgkin's disease (HD) from as many patients with the use of
      the monoclonal antibody Ki-FDC1P, which stains FDCs in paraffin sections. Two
      distinct FDC patterns were distinguishable in the neoplastic areas: pattern A,
      showing FDC networks occupied by nongerminal center cells, often expanded and
      disrupted; and pattern B, with FDCs rare or lacking. Pattern A, with follicle
      occupying cells represented by epithelioid and lymphocytic and histiocytic (L and
      H) cells, was found in about 90% of the cases of nodular lymphocyte predominance
      type and in about half of the cases of nodular sclerosis type, with the follicle
      occupying cells being lacunar cells. In the group of mixed cellularity type,
      approximately one-fifth of the cases exhibited pattern A and in these cases the
      follicle-occupying cells were Sternberg-Reed, Hodgkin's, and epithelioid cells.
      The presence of follicular structures, although abnormal, is a more common
      occurrence in HD than is appreciable with the use of conventional histologic
      methods.

PMID- 1992610
TI  - Use of a probe to repeat sequence of the Y chromosome for detection of host cells
      in peripheral blood of bone marrow transplant recipients.
AB  - In situ hybridization for the Y chromosome (Y-ISH) was used to identify residual
      host cells in the peripheral blood of 51 recipients of sex-mismatched allogeneic
      marrow not depleted of T cells following conditioning with high-dose
      cyclophosphamide and total body irradiation (TBI). One patient who rejected the
      graft showed rapid reappearance of host cells after transient donor marrow
      engraftment. Host cells were detected at low levels in 49 of the remaining 50
      patients. Host peripheral blood mononuclear cells (PBMC) decreased with time and
      reached a plateau at 1.0 +/- 0.2% within four weeks after transplantation, while
      the percentage of host granulocytes (GRAN) reached a plateau at background level.
      The mean absolute numbers of host PBMC or GRAN were less than 0.015 x 10(9)/L and
      did not vary significantly over the period studied. Neither the percentages nor
      the absolute numbers of host PBMC or GRAN were significantly affected by HLA
      matching, TBI dose-intensity, pretransplant remission status, subsequent
      development of acute or chronic graft-versus-host disease or relapse after
      transplantation. The authors conclude that it is common to find a few residual
      host cells in the peripheral blood of allogeneic marrow transplant recipients,
      and the presence of these cells has no clinical significance.

PMID- 1992611
TI  - Inefficacy of moving average algorithm as principal quality control procedure on
      Technicon System H6000.
AB  - Bull's algorithm, in its "revisited" formulation, represents one of the main
      quality control (QC) procedures in several multichannel automatic hematological
      analyzers. Its efficacy, however, is reduced in the theoretical event that red
      blood cells (RBC) and hemoglobin (Hgb) undergo a concomitant analytical drift
      while mean corpuscular volume (MCV) remains unaffected, so that a null effect is
      registered on the related erythrocytic indices: mean corpuscular hemoglobin (MCH)
      and mean corpuscular hemoglobin concentration (MCHC). This particular phenomenon
      has been observed on the Technicon System H6000. Routine daily work was kept in
      control through the use of commercial controls and fresh blood samples: a
      reproducible positive drift of two directly measured erythrocytic parameters (RBC
      and Hgb) and of the calculated hematocrit (Hct) was observed proportional to the
      time of continuous use of the instrument. The usefulness of Bull's QC scheme was
      greatly reduced: it failed to detect "out of control" situation in 38%, 15%, and
      13% of cases in the monitoring of MCV, MCH, and MCHC, respectively, when compared
      with the traditional 2 SD limits on QC samples.

PMID- 1992612
TI  - Measurement of the activated partial thromboplastin time from a capillary
      (fingerstick) sample of whole blood. A new method for monitoring heparin therapy.
AB  - The monitoring of heparin anticoagulation is fraught with difficulties because of
      the need for repetitive venipunctures and the vagaries of sample handling and
      processing. The authors evaluated a new aPTT monitoring system with the potential
      to eliminate many of these difficulties. The Ciba Corning Diagnostics 512
      Coagulation Monitor (CCD monitor) is a hand-held portable instrument that can
      measure an aPTT from a fingerstick sample of capillary whole blood. Fingerstick
      aPTTs from 319 subjects (including controls and individuals on heparin and/or
      warfarin) were compared to venipuncture-derived standard laboratory plasma aPTTs
      using different aPTT reagents on conventional instruments. The correlation
      coefficients between fingerstick and standard aPTTs (0.79-0.83) were the same as
      the correlation coefficient between standard laboratory aPTTs using different
      reagents (0.79). When venipuncture-derived whole blood was compared to
      fingerstick samples on the new instrument, the correlation coefficient was
      excellent (0.93). A high degree of precision, as demonstrated by low coefficients
      of variations, was shown for within-day and between-day testing using the CCD
      monitor and normal controls. This capillary whole blood, aPTT system is the first
      to provide the clinician with a means of rapidly and reliably assessing the
      anticoagulant response to heparin therapy at the bedside, and its use may
      ultimately lead to more efficient and effective therapy overall.

PMID- 1992613
TI  - Granulocytic sarcoma presenting as an epidural mass with acute paraparesis in an
      aleukemic patient.
AB  - Granulocytic sarcomas are rare tumors composed of granulocytic precursor cells.
      They are most commonly encountered in patients with acute myelogenous leukemias
      and myeloproliferative disorders in blast crisis. Rarely, patients presenting
      with granulocytic sarcoma show no evidence of acute leukemia. The authors report
      an aleukemic patient with acute paraparesis from an epidural granulocytic
      sarcoma. Only five such cases have been reported previously. Immunoperoxidase
      stain for lysozyme and chloroacetate esterase stain were used to prove the
      myeloid origin of the tumor cells.

PMID- 1992614
TI  - Munchausen syndrome by proxy documented by discrepant blood typing.
AB  - The authors describe a case of Munchausen syndrome by proxy, a form of child
      abuse, documented by use of routine blood bank serologic procedures. While
      immunohematologic testing has been used in the legal arena to resolve issues of
      disputed paternity and to investigate instances of criminal acts, the authors
      believe this to be the first documented application to this clinical disorder.

PMID- 1992615
TI  - Survival of Gardnerella vaginalis in human urine.
AB  - The authors studied the survival of Gardnerella vaginalis in human urine and
      determined conditions for optimum recovery on agar media. Gardnerella counts
      declined by greater than 99.9% in urine held at 37 degrees C for 24 hours,
      whereas the falloff was negligible at 4 degrees C. Viability was lost after 6
      hours in urine with pH of 5, and only 0.01% cells survived in urine with pH of 7.
      In contrast, greater than 90% cells survived exposure at pH of 6. Dialysis to
      remove small molecular weight (less than 14,000) inhibitors did not enhance
      survival. Co-cultivation with Ureaplasma urealyticum and the addition of glycogen
      improved survival. Maximum recovery from urine required anaerobic incubation on
      enriched agar medium (pH 6.5-7.5) for at least 48 hours. Gardnerella vaginalis
      survives poorly in human urine at 37 degrees C. Culture for these bacteria
      requires prolonged anaerobic incubation.

PMID- 1992616
TI  - Evaluation of a commercial anti-delta EIA kit for detection of antibodies to
      hepatitis delta virus.
AB  - Anti-hepatitis delta virus (anti-HDV) antibodies were measured by solid phase IgG
      and IgM capture radioimmunoassays (RIA) as well as by a competitive binding
      enzyme immunoassay (EIA) in both acute and chronic HDV infections. EIA anti-delta
      test measures total delta antibody without discriminating IgM from IgG anti
      delta. Low titer IgG antibodies were detected by both techniques with equal
      sensitivity. High titer IgG antibodies reached the end point sooner with EIA than
      with RIA (10(-3) versus greater than 10(-6)). When IgM anti-HDV was present
      without accompanying IgG anti-HDV, EIA failed to identify the antibody. Presence
      of high titer rheumatoid factor in the serum and lipemic samples produced false
      positive results by EIA. Usage of undiluted serum samples for EIA probably
      exaggerates the factors contributing to false-positive reaction.

PMID- 1992617
TI  - Accuracy of portable blood glucose monitoring. Effect of glucose level and
      prandial state.
AB  - Glucose was determined on capillary and venous blood samples from 274 adult
      diabetics by three different methodologies: the Glucoscan 2000 and Accu-Check II
      portable glucose meters (capillary) and the Kodak Ektachem 700 analyzer (venous).
      Both glucose meters correlated significantly with the Ektachem results. A
      significant positive bias was found for the Glucoscan compared with Ektachem, not
      found with the Accu-Check II. The Accu-Check performed better than the Glucoscan
      at venous plasma glucose levels less than 1 g/L. The mean error of Glucoscan
      determinations was significantly greater and biased positive when the measurement
      was performed within 4 hours of eating, whereas no such effect was seen with Accu
      Check error. Multiple regression analysis revealed that the Glucoscan measurement
      was independently influenced by both venous plasma glucose and prandial state,
      whereas the Accu-Check II measurement was not dependent on either variable. The
      within-run precision for both glucose meters were comparable.

PMID- 1992618
TI  - Prediction of free phenytoin levels based on [total phenytoin]/[albumin] ratios.
      Potential errors with hypoalbuminemia.
AB  - Therapeutic monitoring of the pharmacologically active (free drug) fraction of
      protein-bound medications (e.g., phenytoin) represents a major diagnostic
      challenge in clinical and laboratory medicine. While free drug levels may be
      beneficial in many clinical situations, current methods for predicting free
      phenytoin concentrations are unreliable and not recommended for general use. The
      authors have demonstrated a linear relationship (r2 = 0.98) between serum levels
      of total and bound phenytoin in 56 patients with seizure disorders. No
      significant correlations were observed when total phenytoin and albumin levels
      were compared independently to measured concentrations of free phenytoin or
      percent free phenytoin. A good correlation (r2 = 0.89) existed between free
      phenytoin levels and [total phenytoin]/[albumin] ratios in patients with normal
      or elevated albumin levels, but significantly weaker correlations were found in
      patients with hypoalbuminemia. Thus, [total phenytoin]/[albumin] ratios may have
      clinical value in predicting free phenytoin levels in uncomplicated patients
      without hypoalbuminemia.

PMID- 1992619
TI  - The analysis of erythrocyte morphologic characteristics in urine using a
      hematologic flow cytometer and microscopic methods.
AB  - Three methods for the examination of erythrocyte morphology in urine are
      described: phase contrast microscopy, microscopy of cytocentrifuged and stained
      preparations, and erythrocyte analysis with the Technicon H1. Analysis with the
      H1 has not been described until now. All methods can be used to discriminate
      between dysmorphic and isomorphic erythrocytes. The red cell distribution width
      was the best H1 parameter for this discrimination. The authors have found a good
      correlation between the microscopic methods. The clinical impact of the three
      methods was studied with urine samples from patients with a confirmed diagnosis.
      The discrimination between renal and nonrenal hematuria is similar with phase
      contrast microscopy and cytocentrifuged preparations. The use of the H1 for this
      discrimination is not recommended.

PMID- 1992620
TI  - Specificity of a reproducible qualitative urine examination is not a constant
      test characteristic.

PMID- 1992621
TI  - Urine collection for the detection of Bence Jones proteinuria.

PMID- 1992622
TI  - On the occasion of Dr. Zeek's 91st birthday.

PMID- 1992623
TI  - Secretin provocation test in the diagnosis of Zollinger-Ellison syndrome.
AB  - The secretin stimulation test has become the preferred provocative test in
      suspected cases of Zollinger-Ellison syndrome. A pure secretin preparation, a
      gastrin-specific radioimmunoassay, and an appropriate sampling sequence are
      important for the proper interpretation of this test. Gastric acid analysis is
      necessary in the assessment of hypergastrinemia to confirm acid hypersecretion
      and exclude achlorhydria. When properly performed and interpreted, the secretin
      provocation test offers a safe, expeditious, and reliable means of evaluating
      patients with hypergastrinemia.

PMID- 1992624
TI  - Cisapride: a new class of prokinetic agent. The ACG Committee on FDA-related
      matters. American College of Gastroenterology.

PMID- 1992625
TI  - That demon rum.

PMID- 1992626
TI  - Nonpropulsive esophageal contractions and gastroesophageal reflux.
AB  - Nonpropulsive esophageal contractions radiologically described as tertiary
      contractions or "corkscrew" esophagus suggest the presence of an underlying
      motility disorder and may lead to impaired acid clearance. The goals of this
      study were to determine the prevalence and role of gastroesophageal reflux (GER)
      in patients with tertiary contractions. Thirty-five consecutive patients with
      spontaneous, repetitive, nonpropulsive esophageal contractions noted on
      esophagography were studied with endoscopy, infusion esophageal manometry, and 24
      h ambulatory pH monitoring. All patients had esophageal symptoms, mainly
      dysphagia, heartburn, and chest pain, but only three were found to have
      esophagitis by endoscopy and biopsy. Nineteen patients had repetitive, nonlumen
      obliterating, nonperistaltic (tertiary) contractions, six had corkscrew
      esophagus, and 10 had forceful, lumen-obliterating simultaneous contractions
      (rosary bead esophagus). Twenty patients (58%) had GER by pH criteria with mean
      values: % time pH less than 4, 40.9; %upright pH less than 4, 41; %supine pH less
      than 4, 44.3%; number of episodes with greater than 5 min of pH less than 4, 12.
      Esophageal motility revealed "nutcracker" esophagus in eight, low LESP in two,
      and nonspecific esophageal motility disorder in 10. Symptoms or severity of
      nonperistaltic contractions did not correlate with GER. Radiologically
      demonstrable free reflux or the presence of heartburn did not predict GER. We
      conclude that 1) GER occurs in up to 58% of patients with nonpropulsive
      (tertiary) esophageal contractions on esophagography, and may play a role in the
      induction of abnormal peristaltic activity of the esophageal body; 2) GER is
      usually not associated with endoscopic evidence of esophagitis or characteristic
      symptoms, and is recognized by 24-h pH monitoring. We speculate that detection
      and treatment of GER may improve the symptomatic management of patients with
      nonpropulsive esophageal contractions.

PMID- 1992627
TI  - The symptom sensitivity index: a valuable additional parameter in 24-hour
      esophageal pH recording.
AB  - Twenty-four-hour esophageal pH monitoring is useful for the quantitative
      measurement of gastroesophageal reflux and for the demonstration of a temporal
      relationship between symptoms and reflux. The symptom index, a numerical score,
      was developed to quantify the association between symptoms and reflux. Because
      the symptom index primarily assesses the specificity of a patient's reflux
      symptoms, we propose to refer to this score as the symptom specificity index.
      Because of certain limitations of this score, we developed and evaluated a new
      score, the symptom sensitivity index, that quantifies the subject's sensitivity
      for reflux. Fifty-two consecutive patients, referred to our laboratory for
      ambulatory 24-h pH recording were studied. Beside the conventional reflux
      variables, both indexes were calculated. Although a statistically significant
      correlation between the indexes was found, discordance between the specificity
      and sensitivity indexes was seen in 17 patients (33%). Based on the findings in
      this study we advocate that the symptom sensitivity index should be used, in
      addition to the symptom specificity index, and incorporated in future pH studies
      to optimalize the interpretation of the results.

PMID- 1992628
TI  - The effect of fasting on 24-hour intragastric acidity and plasma gastrin
      concentration.
AB  - Nine healthy subjects underwent two 24-h studies, either when fed six standard
      meals by mouth or when fasting. There was no significant difference in the median
      integrated 24-h intragastric acidity when fed or when fasting, 805 or 801
      mmol.h/L, respectively. However, the median integrated 24-h plasma gastrin
      concentration was significantly higher when fed than when fasting, 284 pmol.h/L
      and 114 pmol.h/L, respectively (p less than 0.01). There appears to be a normal
      circadian rhythm for intragastric acidity: feeding appears to cause an acute
      decrease of intragastric acidity and to release gastrin, which in turn causes a
      compensatory rise of intragastric acidity. The results of this study suggest that
      the need to reinstate "normal" intragastric acidity is the drive to food-induced
      gastric acid secretion.

PMID- 1992629
TI  - Experience with percutaneous endoscopic gastrotomy in a community hospital.
AB  - Percutaneous endoscopic gastrotomy (PEG) has become the procedure of choice for
      meeting long-term nutritional needs in chronically ill patients. To determine the
      complication and mortality rates in a community hospital, we performed a
      retrospective analysis of 224 patients having PEG placement over a 2-yr period.
      Our study indicates that the morbidity and mortality resulting from PEG placement
      in a community hospital should be similar to that reported from large university
      studies.

PMID- 1992630
TI  - Small bowel enteroscopy and intraoperative enteroscopy for obscure
      gastrointestinal bleeding.
AB  - Intraoperative endoscopy (IOE) is accepted as the ultimate diagnostic procedure
      for completely evaluating the small bowel in patients with obscure
      gastrointestinal (GI) bleeding. Small bowel enteroscopy (SBE) has been reported
      useful in the nonsurgical evaluation of the small intestine in these patients,
      but findings may be limited because of incomplete small bowel intubation and a
      lack of tip deflection. Twenty-three patients underwent 25 SBE exams and
      subsequently had 25 IOE exams during surgical exploration for continued bleeding.
      Patients' bleeding histories averaged 2 yr, with an average transfusion
      requirement of 27 units. Findings on IOE were the same as with SBE in 17/22 (77%)
      of examinations. We conclude that SBE and IOE are comparable in depth of
      insertion and ability to detect small vascular ectasias. Both procedures missed
      pathology due to limited visibility and the evanescent nature of ectasias. Long
      term success in abolishing bleeding with these combined techniques can be
      expected in 55% of these patients. SBE should precede surgery, since the finding
      of diffuse ectasias precludes any benefit from operative intervention.

PMID- 1992631
TI  - Radiographic evaluation of suspected small bowel obstruction.
AB  - Plain abdominal radiographs and enteroclysis studies were reviewed blindly in 117
      consecutive patients undergoing enteroclysis for suspected small bowel
      obstruction. Plain radiographs were unreliably predictive of the presence of
      obstruction as determined by enteroclysis and surgery. Among patients with normal
      or abnormal nonspecific plain radiographs, varying degrees of small bowel
      obstruction were demonstrated by enteroclysis in 22%. Conversely, of patients
      with obstruction on plain radiographs, 42% had either normal enteroclysis studies
      or only minor adhesions. Enteroclysis correctly predicted the presence of
      obstruction in 100%, the absence of obstruction in 88%, the level (proximal vs
      distal) of obstruction in 89%, and the etiology of obstruction in 86% of operated
      patients. Enteroclysis is advocated as the definitive study in patients with
      clinical uncertainty about the diagnosis of small bowel obstruction.

PMID- 1992632
TI  - Colonoscopy during an attack of severe ulcerative colitis is a safe procedure and
      of great value in clinical decision making.
AB  - Thirty-four patients who had severe ulcerative colitis had a colonoscopic
      examination during the attack. The indications were resistance to therapy and/or
      differential diagnostic purposes. Total colonoscopy was performed in 25 cases and
      less extensive examination in nine. Biopsy was taken in 22 cases. No clinically
      significant complications occurred. The procedure helped us to postpone immediate
      surgical intervention in 19 cases. Fourteen of these patients have maintenance
      treatment and are still well after a follow-up median time of 5 yr (6 months to
      10 yr).

PMID- 1992633
TI  - DNA flow cytometry of colorectal carcinoma: correlation of DNA stemlines with
      other prognostic indices.
AB  - DNA flow cytometry (FCM) was performed on paraffin-embedded tissue blocks of 38
      surgically resected colorectal carcinomas (CRC). Forty-seven percent of tumors
      exhibited aneuploidy and 53% were diploid. Seventy-two percent of patients in the
      aneuploid but only 35% in the diploid group were alive after a mean follow-up of
      30.7 and 28.8 months (p = 0.01), and 5-yr survival of 56.7% and 11.7%,
      respectively (p less than 0.05). The site of tumor location, Dukes' stage, and
      serum CEA level did not predict a certain DNA stemline. However, irrespective of
      the ploidy pattern, a serum CEA level greater than 5.0 was associated with a
      higher mortality and poor 5-yr survival (p less than 0.005). Similarly, advanced
      Dukes' stage was associated with higher mortality (p less than 0.05). Forty-six
      percent of the patients with lesions that were Dukes' B2 or advanced stage
      received adjuvant therapy. Eighty-five percent of this subgroup of patients died;
      18% of these patients had aneuploid tumors. The role of FCM in the assessment of
      prognosis of CRC deserves further clinical evaluation in a randomized control
      trial.

PMID- 1992634
TI  - Extracorporeal piezoelectric lithotripsy for complicated bile duct stones.
AB  - Today, common bile duct stones are extracted endoscopically. After endoscopic
      sphincterotomy, nearly 90% of all stones can be removed with a Dormia basket or a
      mechanical lithotripter. Problems are encountered if there are larger stones or a
      duct stenosis. New conservative therapies do serve as an alternative to surgical
      intervention for those few patients in whom endoscopic measures have failed.
      Stone fragmentation can be achieved by extracorporeal shock wave lithotripsy, and
      remaining fragments can be removed endoscopically. So far, authors of most
      reports on the successful disintegration of common bile duct stones used the
      Dornier lithotripter. Stone localization is thus achieved with x-rays, and the
      shock waves are generated by an underwater spark discharge. We report on our
      experiences and results with extracorporeal piezoelectric shock wave lithotripsy
      (EPL) in 19 patients with complicated bile duct stones. With this lithotripter,
      stones are visualized by ultrasound, and shock waves are produced by a
      piezoelectric acoustic generator. Fragmentation was achieved in 84.2%, and
      complete stone removal in 78.9%. These results show that piezoelectric
      lithotripsy is also a useful method for the treatment of complicated bile duct
      stones, as has already been proved for the electrohydraulic- and electromagnetic
      generated shock waves systems. However, the renunciation of general anesthesia
      and the need for analgesia or sedation in only 25% of the treatments render this
      lithotripter system attractive, especially for elderly and frail patients.

PMID- 1992635
TI  - Prognostic factors in alcoholic liver disease. VA Cooperative Study Group.
AB  - Two hundred eighty-one alcoholic patients were prospectively evaluated by
      clinical, biochemical, and histologic parameters during a 4-yr period to assess
      their prognosis. They were stratified into four categories of injury: 1) fatty
      liver (26 patients), 2) acute alcoholic hepatitis (106), 3) cirrhosis (39), and
      4) cirrhosis with superimposed alcoholic hepatitis (111). The rate of survival
      and variables correlating with survival varied according to the group. At 48
      months, 70% of the patients with fatty liver were alive, 58% in the alcoholic
      hepatitis group, 49% in cirrhosis, and 35% in alcoholic hepatitis superimposed
      upon cirrhosis. Within group one, deaths were due to causes unrelated to liver
      disease. In the alcoholic hepatitis group, factors significantly correlating with
      survival were ascites, alanine amino-transferase levels, grams of alcohol
      consumed, continuation of alcohol intake, and clinical severity of disease.
      Survival in patients of group three correlated significantly with prothrombin
      time and histologic severity score. Patients with combined cirrhosis and
      alcoholic hepatitis exhibited the worst prognosis, with the most significant
      predictors of survival being age, grams of alcohol consumed, the ratio of serum
      aminotransferases (AST:ALT) and the histologic and clinical severity of the
      disease. Although a different pattern of correlates was observed for each
      pathologic level of injury, knowledge of the various correlates aids in
      prognostic assessment.

PMID- 1992636
TI  - Hemolytic anemia associated with the use of omeprazole.
AB  - Omeprazole is the first drug designed to block the final step in the acid
      secretory process within the parietal cell. It has been shown to be extremely
      effective in the treatment of peptic ulcer disease, reflux esophagitis, and the
      Zollinger-Ellison syndrome. Although clinical experience with omeprazole is still
      limited, many controlled studies have established the short-term safety of this
      drug. We report the first case of a serious short-term adverse reaction with the
      use of omeprazole: hemolytic anemia. The patient developed weakness, lethargy,
      and shortness of breath 2 days after starting therapy with omeprazole. Two weeks
      after the initiation of therapy, her hematocrit had decreased from 44.1% to
      20.4%, and she had a positive direct Coombs antiglobulin test and an elevated
      indirect bilirubin. After she discontinued the omeprazole, her hemoglobin and
      hematocrit gradually returned to normal. The mechanism by which omeprazole caused
      the patient's hemolytic anemia is uncertain, but physicians should be alerted to
      this possible adverse effect.

PMID- 1992637
TI  - Kawasaki-like syndrome after treatment with mesalazine.
AB  - We report a patient who developed a severe hypersensitivity reaction, including
      rash, lymph node enlargement, fever, hepatitis, and eosinophilia, after
      sulphasalazine therapy. Five years later, he developed a similar reaction after
      exposure to mesalazine, the salicylic compound of sulphasalazine. We conclude
      that patients with known severe systemic reaction to sulphasalazine therapy are
      also at risk for such a reaction when treated with a 5-ASA preparation.

PMID- 1992638
TI  - Congenital duodenal diaphragm: conversion of stable chronic symptoms to subacute
      gastric outlet obstruction by penetrating foreign body.
AB  - Congenital duodenal diaphragms (CDD) are rare lesions that usually become
      symptomatic and require surgery in childhood. We report a patient, who, although
      symptomatic since early childhood, had accommodated to the condition and finally
      required surgical correction in late life after an ingested foreign body
      traumatized the diaphragm, producing subacute gastric outlet obstruction. The
      condition, including the reconstruction of the precipitating event, was diagnosed
      endoscopically prior to surgery.

PMID- 1992639
TI  - Annular pancreas as a cause of extrahepatic biliary obstruction.
AB  - Annular pancreas is a rare congenital abnormality that is increasingly diagnosed
      by endoscopic retrograde cholangiopancreatography (ERCP) in the adult. In this
      population, it can present with duodenal or gastric ulceration, duodenal
      obstruction, pancreatitis, and, rarely, with associated congenital abnormalities.
      Although it has been suggested that biliary obstruction may result from
      associated pancreatitis, such cases have not been reported; primary extrahepatic
      biliary obstruction from a constricting annulus also has not been reported. We
      report such a case, and describe resolution of symptoms and a return to normal
      biochemical tests in a patient. The literature and embryology of annular pancreas
      are reviewed. We suggest that this entity be added to the differential diagnosis
      of extrahepatic biliary obstruction.

PMID- 1992640
TI  - Endoscopic management of postoperative biliary leaks: review of 77 cases and
      report of two cases with biloma formation.
AB  - Biliary leaks are uncommon complications of abdominal surgery. Left untreated,
      they may result in significant morbidity and mortality. The traditional treatment
      has been surgical, but several authors have reported successful endoscopic
      management. We review 77 cases of endoscopically managed postoperative biliary
      leaks reported in the literature over the past 15 yr. Endoscopic treatment was
      technically successful in 95% of cases, and resulted in biliary leak healing in
      82%. Cystic stump leaks had a better prognosis for healing compared with common
      bile duct or hepatic duct leaks. We also present two additional cases of
      postoperative biliary leaks with biloma formation successfully treated with
      endoscopic stent placement. Our experience lends additional support to endoscopic
      management as the preferred approach to postoperative biliary leaks.

PMID- 1992641
TI  - Endoscopic management of retained cystic duct stones.
AB  - The finding of residual common bile duct stones after cholecystectomy is a
      relatively frequently encountered problem for which effective nonoperative
      therapy exists. Retained stones in a cystic duct remnant are very rare. We
      present a case of multiple retained stones in a long variant cystic duct remnant
      following cholecystectomy and common duct exploration, which was successfully
      managed with endoscopic sphincterotomy and balloon extraction.

PMID- 1992642
TI  - Inflammatory pseudotumor of the liver associated with acute myelomonocytic
      leukemia.
AB  - A patient with inflammatory pseudotumor of the liver associated with acute
      myelomonocytic leukemia (M4) is reported. He had spiking fever, epigastralgia,
      and elevated levels of serum C-reactive protein (CRP) and alkaline phosphatase
      (ALP). Ultrasonography showed a hypoechoic mass in the liver, and ultrasonically
      guided fine needle aspiration biopsy of the mass revealed that it was composed of
      fibrous connective tissue infiltrated with plasma cells, eosinophils, and
      neutrophils. Accordingly, a diagnosis of inflammatory pseudotumor of the liver
      was made. Marked reduction in the size of the lesion and a decrease of the levels
      of the CRP and ALP occurred without specific treatment. We emphasize the
      importance of ultrasonically guided aspiration biopsy in diagnosis of
      inflammatory pseudotumor of the liver without the need for surgery.

PMID- 1992643
TI  - Omeprazole for peptic ulcer in Crohn's disease.

PMID- 1992645
TI  - Crohn's colitis in patients with diverticular disease.

PMID- 1992644
TI  - Voltaren (diclofenac sodium)-induced ileocolitis.

PMID- 1992646
TI  - Comment on oral sodium phosphate with standard polyethylene glycol-based lavage
      solution (Golytely) content.

PMID- 1992647
TI  - Presence of Helicobacter pylori in gastric juice.

PMID- 1992648
TI  - Budd-Chiari syndrome as a complication of the catheterization of the subclavian
      vein.

PMID- 1992650
TI  - An overview of pregnancy in women with underlying renal disease.
AB  - This is a report of a retrospective study of the effects of preexisting
      glomerular disease and pregnancy on each other. Two hundred forty pregnancies in
      166 Japanese women who delivered between 1970 and 1988 were analyzed. There were
      206 (86%) live births, 14 (6%) perinatal deaths, and 20 (8%) spontaneous
      abortions. Perinatal loss was greatest in women with hypertension and/or
      glomerular filtration rate (GFR) less than 70 mL/min before conception. Pregnancy
      did not appear to adversely affect the underlying glomerular disease if GFR was
      greater than 70 mL/min and blood pressure was below 140/90 mm Hg. However, with
      moderately impaired renal function (creatinine greater than 124 mumol/L [1.4
      mg/dL] or GFR less than 50 mL/min), the long-term prognosis was poorer, despite
      generally favorable obstetrical outcomes. Gravidas with membranoproliferative
      glomerulonephritis had the highest rates of hypertension (29%) and decreased
      renal function (33%) at final follow-up, ie, the type and severity of
      glomerulonephritis had a major impact on clinical course.

PMID- 1992649
TI  - Osmotic and volume control of vasopressin release in pregnancy.
AB  - This article, a review of factors controlling vasopressin (AVP) release in
      pregnancy, extends our contribution to a symposium in this journal published in
      1987 (vol X, pp 270-275). Body tonicity decreases (approximately 10 mOsm/kg) very
      early in pregnancy due to decrements in the osmotic thresholds for AVP release
      and thirst. In addition, the metabolic clearance rate (MCR) of AVP markedly
      increases between gestational week 10 and midpregnancy, and is paralleled by the
      appearance and increase of circulating cystine aminopeptidase (vasopressinase),
      while the MCR of 1-deamino-8-D-AVP (DDAVP), an analogue resistant to inactivation
      by the enzyme, changes little in pregnancy. These increases (MCR of AVP and
      plasma vasopressinase) may explain certain syndromes of transient diabetes
      insipidus (DI) that complicate gestation. Finally, mechanisms responsible for the
      altered osmoregulation in pregnancy are obscure, but chorionic gonadotropin may
      be involved in the changes during human gestation.

PMID- 1992651
TI  - Specific controversies concerning the natural history of renal disease in
      pregnancy.
AB  - Whether or not pregnancy adversely affects the natural course of underlying
      primary renal disease, and whether fetal outcome is influenced by the type of
      renal disease per se are controversial issues. We retrospectively analyzed the
      fetal and maternal outcome in 148 women with various, biopsy-proven histological
      types of primary chronic glomerulonephritis (GN), including IgA GN (52 patients),
      membranous GN ([MGN] 20 patients), membranoproliferative type 1 GN ([MPGN] 58
      patients), focal and segmental glomerulosclerosis ([FSGS] 13 patients), and
      minimal change nephrotic syndrome ([MCNS] 22 patients), who were pregnant (with a
      total of 290 pregnancies) after the clinical onset of GN, and in 104 women with
      reflux nephropathy (with a total of 254 pregnancies). Fetal outcome was poor in
      the presence of uncontrolled hypertension, nephrotic range proteinuria, and/or
      impaired renal function at conception or early in gestation, whatever the type of
      renal disease. An accelerated, more rapid than expected, worsening of maternal
      renal function was observed in five GN patients of whom four (two IgA, two MPGN)
      had serum creatinine (Scr) levels greater than 160 mumol/L (1.8 mg/dL) early in
      gestation, and in five patients with reflux nephropathy whose Scr at conception
      ranged from 180 to 490 mumol/L (2.0 to 5.5 mg/dL).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1992653
TI  - Dialysis, transplantation, and pregnancy.
AB  - Women on regular dialysis are usually infertile, but contraception should not be
      neglected. Pregnancy is invariably complicated and poses excessive risks, with an
      uncertain and low chance of success. Even when therapeutic abortion is excluded,
      the live birth outcome at best is 19%. Renal transplantation usually reverses
      abnormal reproductive function and comprehensive pre-pregnancy counseling is
      essential, with discussion of all implications, including the harsh realities of
      long-term maternal survival. In this survey of 2,309 pregnancies in 1,594 women,
      therapeutic abortion was undertaken in 27% of conceptions and the spontaneous
      abortion rate was 13%. Of the conceptions that continued beyond the first
      trimester, 92% ended successfully. In most, renal function was augmented in
      pregnancy, with transient deterioration in late pregnancy (with or without
      proteinuria). Permanent renal impairment occurred in 15% of pregnancies. There
      was a 30% chance of developing hypertension, preeclampsia or both. Preterm
      delivery occurred in 50%, and intrauterine growth retardation in 25% of
      pregnancies. Despite its pelvic location, the transplanted kidney rarely produced
      dystocia and was not injured during vaginal delivery. Cesarean section should be
      reserved for obstetric reasons only. Neonatal complications include respiratory
      distress syndrome, leukopenia, thrombocytopenia, adrenocortical insufficiency,
      and infection. No predominant or frequent developmental abnormalities have been
      described and data on infancy and childhood are encouraging. For the future more
      work is needed to improve pre-pregnancy assessment criteria, to understand the
      mechanisms of gestational renal dysfunction and proteinuria, to assess the side
      effects and implications of immunosuppression in pregnancy, and to elucidate the
      remote effects of pregnancy on both renal prognosis and the offspring.

PMID- 1992652
TI  - Maternal and fetal complications in pregnant women with systemic lupus
      erythematosus.
AB  - Recent studies provide important insights into maternal complications in patients
      with systemic lupus erythematosus (SLE) established before onset of pregnancy.
      Exacerbations or relapse occur during the course of pregnancy and immediately
      postpartum in 25% to 60% of pregnancies. However, the likelihood of increased
      clinical activity of SLE during pregnancy is influenced by signs of activity
      present at onset of pregnancy. In the absence of signs of clinical activity for
      at least 6 months before conception, relapses occur in about one third, whereas
      in patients with clinical activity at onset of pregnancy, persistent activity or
      exacerbations occur in approximately two thirds. Fetal survival in these patients
      parallels the incidence of SLE activity: 85% to 95% in the group with inactive
      disease at conception and 50% to 80% in subjects with active disease at onset of
      pregnancy. The introduction of an assay for anticardiolipids has led to a new
      concept for the pathogenesis of autoimmune disease, namely immune-related
      thrombosis. Recent studies suggest that this mechanism may play an important role
      in clinical episodes in SLE, involving late fetal death and maternal arterial and
      venous thrombosis.

PMID- 1992654
TI  - The renal lesion of preeclampsia revisited.
AB  - Controversy has existed about the relative contributions of subendothelial
      "fibrinoid" deposits and endothelial cell swelling to the thickened glomerular
      capillary wall and reduced lumen in preeclampsia. A morphometric analysis of the
      ultrastructural changes in the glomerulus in preeclampsia showed that
      subendothelial fibrinoid deposits were a significant feature of biopsies during
      pregnancy, but were absent in many biopsies in the postpartum period. These
      deposits disappear progressively in the first week after delivery. Capillary wall
      changes with reduplication of glomerular capillary walls and mesangial
      interposition are another prominent feature of preeclampsia. These changes
      resolve gradually and may present for as long as 18 months. Foam cells in
      glomeruli are rarely found in biopsies during pregnancy, but appear during
      resorption of the subendothelial deposits in the postpartum period. Electron
      dense droplets in glomerular epithelial cells are a characteristic feature of
      preeclampsia. Immunogold labeling demonstrates that they contain albumen,
      immunoglobulins, fibrinogen, and complement. Fibrinogen is usually present in an
      inner electron-dense core in a droplet. IgM is usually in a relatively
      translucent outer part of the droplet. Other proteins are diffusely distributed.
      Segmental hyalinosis is a change that closely resembles the changes of
      preeclampsia, and segmental lesions may appear during preeclampsia and disappear
      after pregnancy.

PMID- 1992655
TI  - Continuous ambulatory peritoneal dialysis as long-term treatment for end-stage
      renal disease.

PMID- 1992656
TI  - Ten years' experience with continuous ambulatory peritoneal dialysis.
AB  - Up to January 1989, 171 patients were trained at our center on continuous
      ambulatory peritoneal dialysis (CAPD), and 17 on continuous cyclic peritoneal
      dialysis (CCPD). Over 10 years, we have gained 5,068 patient-months experience.
      Patient survival was 60% and 31% at 5 and 10 years, respectively. In contrast,
      diabetics had a survival of 32% at 5 years. Major complications included 499 new
      episodes of peritonitis, 304 exit-site infections, 22 hernias, five bowel
      perforations, one hydrothorax, and three episodes of sclerosing encapsulating
      peritonitis. Our technique survival has been 62% and 40% at 5 and 10 years,
      respectively. We believe that CAPD is a viable dialysis technique for long-term
      treatment of chronic renal failure and it should be offered as an option to
      intermittent hemodialysis.

PMID- 1992657
TI  - Continuous ambulatory peritoneal dialysis: ten years at one facility.
AB  - A review of continuous ambulatory peritoneal dialysis (CAPD) performed at one
      facility over a period of 10 years showed that age and type II diabetes mellitus
      were associated with the worst technique survival. The median survival of
      patients entering CAPD was not significantly different when the etiology of renal
      failure was chronic glomerulonephritis (CGN; 27 months), chronic interstitial
      nephritis (CIN; 21 months), diabetes mellitus type I (21 months), or hypertension
      (16 months). Patients with diabetes mellitus type II had significantly (P less
      than 0.05) worse survival (11 months). A patient remaining on CAPD 6 months had a
      55% to 60% chance of remaining on therapy at 2 years and a 47% chance at the end
      of 3 years, whereas a patient with diabetes mellitus type II had a 34%
      conditional probability of remaining on dialysis at 2 years and 18% at 3 years.
      Sex, race, and educational achievement were not important determinants of
      dialysis technique survival. Studies are indicated to identify predictors of a
      poor dialysis experience.

PMID- 1992658
TI  - Rate-related recirculation: the effect of altering blood flow on dialyzer
      recirculation.
AB  - Increasing dialyzer blood flow to enhance the efficiency of dialysis has become
      commonplace. While it is recognized that this procedure may increase
      recirculation, the resulting extent of recirculation has not previously been
      examined. We studied 16 patients with various levels of recirculation and found
      it to average 8.5% at a blood flow of 50 mL/min, 14.9% at 200 mL/min, and 22.5%
      at 316 mL/min. This rate-related recirculation has a significant impact on
      dialyzer urea clearance and should be taken into account in the dialysis
      prescription.

PMID- 1992659
TI  - The effects of reprocessing cuprophane and polysulfone dialyzers on beta 2
      microglobulin removal from hemodialysis patients.
AB  - To further define the relationship between dialyzer reuse and the removal of beta
      2-microglobulin (beta 2M) during dialysis, 26 patients who received hemodialysis
      were studied. Thirteen patients were dialyzed with conventional cuprophane
      dialyzers, and thirteen patients were dialyzed with high-flux polysulfone
      dialyzers. Patients in each group were dialyzed with only new dialyzers during
      the primary-use phase of the study, and reprocessed dialyzers during the reuse
      phase. Dialyzers were used six times during the reuse phase. Serum beta 2M levels
      were measured both predialysis and postdialysis, and adjusted for fluid loss.
      Dialysis with conventional cuprophane new dialyzers during the primary-use phase
      of the study resulted in a 3.3% increase in serum beta 2M levels, and a 2.4%
      increase in serum beta 2M levels during the reuse phase. The difference in the
      change of the concentration of beta 2M between primary-use and reuse phases was
      not statistically significant. Dialysis with high-flux polysulfone new dialyzers
      during the primary-use phase was associated with a decrease of 59.5% in the mean
      postdialysis concentration of serum beta 2M compared with the predialysis level.
      A corresponding decrease of 62.6% in serum beta 2M levels was observed after
      dialysis with high-flux polysulfone reprocessed dialyzers during the reuse phase.
      These data show no evidence of an adverse effect on the clearance of beta 2M
      during dialysis from the reuse of dialyzers up to six times. The results confirm
      previous studies that have reported that high-flux dialysis with polysulfone
      dialyzers removes substantial amounts of beta 2M, and dialysis with conventional
      cuprophane dialyzers does not.

PMID- 1992660
TI  - Concomitant iron and aluminum mass transfer following deferoxamine infusion
      during hemofiltration.
AB  - Variable tissue overloading can alter the removal rate of iron and aluminum from
      uremics. Owing to its higher affinity to deferoxamine (DFO) and higher plasma
      concentrations, Fe could impair Al removal in cases of simultaneous body burden.
      Fe and Al plasma kinetics and mass transfer were therefore studied in 12 uremic
      patients with different Fe and Al status: six with normal ferritin levels (less
      than 400 micrograms/L [ng/mL]), and Al 1.4 to 4.7 mumol/L (40 to 131
      micrograms/L) (group A); six with increased ferritin (greater than 2,000
      micrograms/L), and Al 1.7 to 17 mumol/L (47 to 476 micrograms/L) (group B). DFO
      (40 and 80 mg/kg in a random sequence) was administered once a week during the
      first hour of the first hemofiltration (HF). The results show that in both groups
      and with both DFO doses, maximum Fe and Al mass transfer was achieved in the
      first and second HF, respectively. The 80-mg/kg dose of DFO significantly raised
      Al mass transfer in both groups, whereas Fe mass transfer was only slightly
      affected. Even though plasma Fe levels were almost always higher than Al, Al mass
      transfer eventually exceeded that of Fe, in both Fe-normal and Fe-overload
      patients. The bias towards Al in mass transfer was enhanced in both groups in the
      second HF, and at the higher DFO doses. Thus, DFO once a week reduced Fe loss to
      less than 30 mumol/wk in patients with normal ferritin levels. In both Fe and Al
      overloaded patients, Al can be removed, and Al mass transfer may often exceed Fe
      mass transfer, depending on the degree of tissue burden, the time from DFO
      infusion, and the DFO dose.

PMID- 1992662
TI  - Community-acquired acute renal failure.
AB  - Acute renal failure usually occurs during hospitalization, but may also be
      present on admission to the hospital. To define the causes and outcomes of
      community-acquired acute renal failure, we undertook a prospective study of
      patients admitted to the hospital with acute elevations in serum creatinine
      concentrations. Over a 17-month period, all admission serum creatinine
      determinations were screened for patients with values greater than 177 mumol/L (2
      mg/dL). These values were compared with baseline creatinines to select patients
      with an acute elevation in serum creatinine occurring outside the hospital. One
      hundred patients were entered into the study, with an overall incidence of 1% of
      hospital admissions. Seventy percent of the patients had prerenal azotemia, 11%
      had intrinsic acute renal failure, 17% had obstruction, and 2% could not be
      classified. Mean peak serum creatinine (318 +/- 18 mumol/L [3.6 +/- 0.2 mg/dL])
      and mortality (7%) was lowest in the group with prerenal azotemia. In this group,
      volume contraction due to vomiting, decreased fluid intake, diarrhea, fever,
      glucosuria, or diuretics was the most common underlying cause. The group with
      intrinsic acute renal failure had the most severe renal failure and the highest
      mortality (55%). Although ischemic acute tubular necrosis is the most common
      cause of hospital-acquired intrinsic acute renal failure, this etiology was seen
      in only one patient. Drug-induced nephrotoxicity and infection-related causes
      were the most common underlying etiologies of intrinsic acute renal failure.
      Obstructive renal failure had a mortality of 24% and was most commonly due to
      benign prostatic hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1992661
TI  - Calcitriol metabolism in patients with chronic renal failure.
AB  - We studied calcitriol metabolism in white patients with chronic renal failure and
      in age- and sex-matched normal subjects. The plasma levels of calcitriol (21.9 +/
      1.6 pg/mL, n = 7, v control, 37.4 +/- 2.9 pg/mL, P less than 0.001), metabolic
      clearance rate (MCR) of calcitriol (0.45 +/- .01 mL/min/kg v control, 0.58 +/-
      .02 mL/min/kg, P less than 0.001), and production rate (PR) of calcitriol (14.2
      +/- 1.0 ng/kg/d v control, 31.8 +/- 3.2 ng/kg/d, P less than 0.001) were
      significantly lower in patients with moderate renal failure (average creatinine
      clearance, 0.59 +/- 0.01 mL/s [35.1 +/- 6.1 mL/min]) when compared with the
      respective values of normal control subjects. The MCR of calcitriol was
      determined again in patients with renal failure after they received calcitriol, 1
      microgram/d, for 1 week. The MCR remained unchanged (0.46 +/- .04 mL/min/kg, n =
      7) and plasma levels of calcitriol were increased to 34.6 +/- 2.77 pg/mL. The
      mechanism by which the MCR of calcitriol decreases in renal failure is partly due
      to the presence of inhibitory factors of degradation enzymes in uremic plasma.
      When the ultrafiltrates of uremic plasma obtained from hemodialysis patients were
      infused to normal Sprague-Dawley rats, the MCRs of calcitriol (0.20 +/- .01
      mL/min/kg, n = 6) were markedly suppressed in comparison to those of rats infused
      with the ultrafiltrates of normal plasma (0.37 +/- .01 mL/min/kg, n = 6, P less
      than 0.001). The uremic plasma also contained factors that inhibit the synthesis
      of calcitriol. We conclude that metabolic degradation of calcitriol is decreased
      in patients with renal failure, and uremic plasma contains inhibitory factors
      that suppress the synthesis and degradation of calcitriol.

PMID- 1992663
TI  - Enalapril-associated anemia in renal transplant recipients treated for
      hypertension.
AB  - We encountered a renal transplant recipient who developed an unexplained 0.09
      decrease in hematocrit value while taking enalapril for hypertension, which
      reversed when the drug was stopped. This experience, and a previous similar case
      report, prompted a review of all our 27 transplant patients treated with
      enalapril. Of these, 10 patients (37%) had developed an otherwise unaccounted for
      anemia: the pre-enalapril hematocrit value was 0.42 +/- 0.01 and it decreased to
      the nadir value of 0.33 +/- 0.01 (P less than 0.001) within 12.3 +/- 0.9 weeks
      after initiation of 9 +/- 2.4 mg of enalapril daily; enalapril was stopped in
      seven patients and their anemia resolved within 9.1 +/- 0.7 weeks to a final
      hematocrit value of 0.40 +/- 0.01. The remaining three patients were maintained
      on enalapril at their physicians' discretion, without further decrease in
      hematocrit values. No appreciable changes in drug regimens, clinical course, or
      other laboratory parameters were noted during this period. A causal relationship
      between enalapril and anemia was suggested by the effect of drug withdrawal and
      rechallenge on hematocrit in one of the patients. There were no statistically
      significant differences in baseline clinical and laboratory characteristics
      between those patients who did (group I) and those who did not (group II) develop
      enalapril-associated anemia, with the exception of a normal hematocrit value of
      0.42 +/- 0.01 in group I versus a lower hematocrit value of 0.36 +/- 0.02 in
      group II (P less than 0.05). We conclude that enalapril should be considered in
      the differential diagnosis of anemia following renal transplantation.
      Susceptibility to this effect might emanate from the immunosuppressed state.

PMID- 1992664
TI  - Evaluation of fine-needle aspiration biopsy in the diagnosis of renal transplant
      dysfunction.
AB  - Fine-needle aspiration biopsy (FNAB) was performed in 41 renal transplant
      patients to assess its value in the diagnosis of the cause of graft dysfunction.
      The procedure was used on 71 occasions, and in each case a clinical diagnosis was
      made and compared with the cytological diagnosis made independently by a
      pathologist. When available, core biopsy histopathology was used to confirm the
      final diagnosis. Fifty-seven (80%) of the aspirates yielded adequate material. A
      clinical diagnosis of acute cellular rejection (ACR) was made in 21 patients, 18
      (78%) of whom showed confirmatory immune activation on FNAB. The clinical
      diagnosis of either acute tubular necrosis (ATN) or cyclosporine toxicity was
      confirmed in 31 (91%) of 34 aspirates. In eight aspirates, the cytological
      diagnosis was different than that made clinically. Humorally mediated vascular
      rejection, and lymphocytosis secondary to causes other than rejection, such as
      viral infection, were considered as possible causes of this discrepancy. Provided
      that adequate samples are obtained. FNAB is valuable in the clinical management
      of renal transplant patients. Its accuracy should not be overestimated and the
      results obtained should be evaluated in the light of the overall clinical
      picture.

PMID- 1992665
TI  - Serial glomerular and tubular dynamics in thyroidectomized rats with remnant
      kidneys.
AB  - Serial measurements were performed in Munich-Wistar rats with five-sixths
      nephrectomy that had undergone prior selective thyroidectomy (Tx group) or
      thyroidectomy with thyroxine replacement (TxT4 group) to determine the effects of
      Tx on glomerular and tubular dynamics in relation to Tx attenuation of renal
      failure progression. At 1 week, inulin clearance rates (Cin) in TxT4 and Tx rats
      were 0.367 +/- 0.171 and 0.120 +/- 0.036 mL/min, respectively, different at P
      less than 0.01. Corresponding single-nephron filtration rate (SNGFR), glomerular
      plasma flow (QA), glomerular transcapillary hydraulic pressure (delta P), and
      proximal tubular reabsorption (Jv) were all reduced in Tx compared with TxT4 rats
      (P less than 0.01). Protein excretion (UPROT) was 151 +/- 40 in TxT4 rats, and 9
      +/- 5 mg/d in Tx animals. Glomerular mesangial matrix expansion and focal
      tubulointerstitial changes were more frequent in TxT4 than Tx rats. By 4 weeks,
      Cin, SNGFR, QA, glomerular ultrafiltration coefficient (Kf) and Jv were similar
      in Tx and TxT4. Only glomerular capillary pressure (PGC) remained lower in Tx
      rats (35 +/- 3 v 50 +/- 3 mm Hg in TxT4, P less than 0.001). UPROT was 161 +/- 24
      in TxT4 and 17 +/- 12 mg/d in Tx rats. While 7% +/- 4% of glomeruli showed focal
      sclerosis in TxT4 rats, there was none in the Tx group. Maximal glomerular planar
      area increased between 1 and 4 weeks in the TxT4 group, but not in the Tx group.
      However, this measurement was not significantly different between TxT4 and Tx
      glomeruli at 1 or 4 weeks. Minimal focal tubulointerstitial changes were found in
      TxT4, but there were not progressive from those observed at 1 week. The reduced
      PGC at 1 week was the result of a disproportionately greater increase in afferent
      (RA) than efferent arteriolar resistance (RE) in Tx rats (P less than 0.025);
      however, at 4 weeks, both RA and RE had decreased to values identical to those in
      TxT4 animals and the lower PGC in Tx rats was the result of a reduced mean
      arterial pressure. In conclusion, a reduced PGC was the sole functional correlate
      of decreased proteinuria and glomerulosclerosis afforded by Tx in this partial
      nephrectomy model. Suppression of either nephrectomy-related hypertrophy or
      tubulointerstitial injury by Tx could not be excluded as at least partially
      protective factors.

PMID- 1992667
TI  - Group B streptococcus: an unusual cause of severe peritonitis in young children
      treated with continuous ambulatory peritoneal dialysis.
AB  - Peritonitis in continuous ambulatory peritoneal dialysis (CAPD) patients is only
      rarely caused by beta-hemolytical streptococci species. We describe two young
      children, aged 15 months and 5 years, respectively, who presented an unusually
      severe course of peritonitis due to group B beta-hemolytical streptococci. This
      course of the disease showed a strong similarity with neonatal streptococcal
      septicemia. In neonates, IgG2 deficiency is thought to be partly responsible for
      the severity of this condition. This may also be true for young children treated
      with CAPD, since IgG2 deficiency has been established for children.

PMID- 1992666
TI  - Recurrent acute glomerulonephritis.
AB  - Biopsy-proven recurrent acute glomerulonephritis (AGN) is extremely rare and is
      usually seen in children with acute, well-defined streptococcal infections. We
      present here a patient with recurrent AGN in the absence of chronic bacterial
      infection. The subject, an 80-year-old man, had eight episodes of acute nephritic
      syndrome following upper respiratory tract infection. No abnormalities were
      detected during remissions. Renal biopsies during two of those episodes showed
      typical postinfectious acute exsudative endocapillary glomerulonephritis, while
      results of another biopsy performed during remission were normal.

PMID- 1992668
TI  - Heparin skin necrosis: delayed occurrence in a patient on hemodialysis.
AB  - A case of skin necrosis in a patient receiving intravenous (IV) heparin during
      routine intermittent hemodialysis is reported. Multiple erythematous, tender
      lesions developed over the abdomen and thighs and rapidly became necrotic.
      Biopsies showed fibrin thrombi in the dermal venules and capillaries, but no
      cellular infiltrate. The patient was in her third month of regular hemodialysis.
      Skin necrosis associated with the use of heparin usually occurs within 2 weeks of
      beginning heparin therapy and has not been reported in patients receiving heparin
      with hemodialysis. Possible mechanisms, including acquired antithrombin III
      deficiency leading to heparin-induced skin necrosis, are discussed.

PMID- 1992669
TI  - Polyuria: simple and mixed disorders.

PMID- 1992670
TI  - Urea kinetic modeling (UKM)

PMID- 1992672
TI  - The kidney and hypertension in pregnancy. Proceedings of a symposium. July 21,
      1990, Tokyo.

PMID- 1992671
TI  - Exercise tolerance before and after correction of anemia with epoetin alfa.

PMID- 1992673
TI  - Renal hemodynamics in normal and hypertensive pregnancy: lessons from
      micropuncture.
AB  - Rats are an excellent animal model in which to study the changes in renal
      hemodynamics associated with normal pregnancy. Midterm pregnant rats exhibit a
      maximal renal vasodilation leading to increases in glomerular filtration rate
      (GFR) and renal plasma flow (RPF). Micropuncture studies in midterm pregnant
      Munich-Wistar rats have shown that single-nephron GFR (SNGFR) increases, due
      entirely to increases in plasma flow and, importantly, glomerular capillary blood
      pressure (PGC) remains unchanged in normotensive pregnancy, due to parallel and
      proportionally similar reductions in preglomerular (RA) and efferent (RE)
      arteriolar resistance. Despite the chronic gestational renal vasodilation,
      pregnancy in normotensive rats with either normal kidneys or a variety of
      underlying diseases, causes no adverse changes in renal function, perhaps because
      the glomeruli are protected from damaging high PGC. In the presence of systemic
      hypertension, the renal vasodilation of pregnancy could put the maternal kidney
      at risk of injury due to increases in PGC. There are few renal functional studies
      in preexisting, essential hypertension, but micropuncture studies in
      spontaneously hypertensive rats (SHRs) have shown that repetitive pregnancies in
      SHRs cause no functional impairment. Surprisingly, SHRs demonstrated no
      gestational renal vasodilation, although gestational decreases in peripheral
      resistance certainly occur in the SHR. This absence of gestational renal
      vasodilation may be a protective mechanism; it remains to be determined whether
      hypertensive states in which renal vasodilation does occur are associated with
      increased risk to the maternal kidney.

PMID- 1992674
TI  - Deja vu?

PMID- 1992675
TI  - Cancer by industry: analysis of a population-based cancer registry with an
      emphasis on blue-collar workers.
AB  - This paper uses information on occupation and industry routinely collected in a
      state-based cancer registry to assess potential associations between work place
      exposures and cancer incidence. Industry-specific proportional cancer incidence
      ratios (PCIR) were calculated by race and sex for all individuals and for white
      males with blue-collar occupations. Expected numbers of cancers were derived both
      from cancers occurring among all occupations and just among blue-collar
      occupations. This latter analysis was done as a control for differences in the
      prevalence of life-style habits between blue- and white-collar workers. Increased
      lung cancer PCIR were seen in most industries previously reported to be
      associated with lung cancer risk. The effects of socioeconomic status on these
      results are discussed. Other results include an increased ratio of melanoma in
      blue-collar white male rubber and plastic product workers, an increased ratio of
      non-Hodgkin's lymphomas in motor vehicle manufacture workers, and an increased
      PCIR of chronic lymphocytic leukemia in general construction workers. Uterine
      cancer was increased in proportion in white females for a number of industries
      including rubber and plastic product manufacture, apparel manufacture, and
      electrical equipment manufacture.

PMID- 1992676
TI  - Increased risk of lung cancer in the melting department of a second Ontario steel
      manufacturer.
AB  - A study of lung cancer among workers at an electric arc steel making operation
      was performed to follow up on the observation of a lung cancer cluster in the
      melt shop of another plant. The study group comprised 335 deceased men identified
      from plant records. Eight of thirty men who had ever worked in the pouring pit
      area died of lung cancer (PMR 276; p less than 0.01), but increased risk was not
      found elsewhere in the melting department. There was a significant trend in lung
      cancer risk with the length of employment in the pit area during a time window 18
      30 years before death. Smoking data suggested that smoking alone could not
      account for the increased risk. An industrial hygiene assessment found present
      exposures to carcinogenic metals and silica to be within current guidelines. No
      polycyclic aromatic hydrocarbons were detected. This is the second steel plant
      for which we have found increased lung cancer risk in the pouring areas. The
      causative factors have not yet been identified.

PMID- 1992677
TI  - Respiratory symptoms and pulmonary function in chicken catchers in poultry
      confinement units.
AB  - To evaluate the respiratory consequences of working in poultry confinement units,
      we completed a cross-sectional epidemiologic study of respiratory symptoms and
      pulmonary function in 59 chicken catchers. The results were compared to a
      published reference standard of nonexposed blue-collar workers. Chicken catchers
      reported a high rate of acute symptoms associated with work in poultry houses.
      They also reported statistically significant higher rates for chronic phlegm
      (39.0%) and chronic wheezing (27.1%) than nonexposed blue-collar workers. Chicken
      catchers had significant decrements over a work shift in forced vital capacity (
      2.2%) and forced expiratory volume in 1 sec (-3.4%), and there was suggestive
      evidence that they had decreased preshift pulmonary function compared with
      nonexposed blue-collar workers. These results indicate that chicken catchers are
      at risk for respiratory dysfunction and emphasize the need to develop measures to
      minimize their exposure to respiratory toxicants in poultry confinement units.

PMID- 1992678
TI  - Outcome of the abduction external rotation test among manual and office workers.
AB  - Reactions during the Abduction External Rotation (AER) test were studied among 71
      platers and 70 assemblers exposed to vibratory tools and manual work and 45
      unexposed white collar workers. The frequency of positive neurological reactions
      was 31% among the platers, 6% among the assemblers, and 16% among the white
      collar workers. Platers reported the highest fatigue rates in the shoulder
      regions during the test. A positive association was noted between a pathological
      AER test and current problems in the neck/scapula or shoulder/upper arm regions,
      day- or night-time numbness in the hands, tension neck, and carpal tunnel
      syndrome. Age, length of daily vibration exposure, and vibration acceleration
      level were also positively associated with a positive AER test outcome. The
      results indicate that the outcome of the AER test is sensitive to neck and
      shoulder disorders but also, to some extent, to the carpal tunnel syndrome.

PMID- 1992679
TI  - Use of "time windows" to investigate lung cancer latency intervals at an Ontario
      steel plant.
AB  - This paper describes an application of the time windows method to an examination
      of the temporal pattern of lung cancer risk among steel workers. Case-control
      methodology was utilized. The cases were 36 men who had died of lung cancer and
      the controls were 289 men who had died of any other cause. The number of years of
      employment in the steel pouring area was used as a surrogate measure of exposure.
      The data were examined by contingency table analysis and by logistic regression,
      which permitted adjustment for exposures in multiple time windows and the use of
      continuous, rather than categorical, measures of exposure. It was found that lung
      cancer risk was associated with exposures occurring between 18 and 30 years
      before death. It cannot yet be determined whether this time course reflects a
      biological response or the temporal pattern of exposure to an as yet unidentified
      toxic agent.

PMID- 1992680
TI  - High concentration of N-nitrosodiethanolamine in a diluted commercial cutting
      fluid.

PMID- 1992682
TI  - The development of training in occupational medicine in the United Kingdom.

PMID- 1992681
TI  - The discovery of mesothelioma in the northwestern Cape Province in the Republic
      of South Africa.

PMID- 1992683
TI  - The occupational medicine consultant.
AB  - The occupational medicine consultant emerged in a few areas of the country during
      the 1940s. The concept is growing in popularity, with some recent evidence
      indicating that it may be the dominant career path for residency trained
      specialists in occupational medicine. The services provided to industry, labor,
      and government do not appear to compete with traditional occupational medicine
      positions. The manpower shortage in occupational physicians promises to fuel the
      growth opportunity for occupational medicine consultants. The major concerns at
      this time are the adequacy of liability insurance carried by the consultants and
      the possibility that their activities will too often be related to crisis
      situations rather than to the development of preventive medical programs with
      their clients.

PMID- 1992684
TI  - Worker health and safety: the occupational medicine training factor.

PMID- 1992685
TI  - Epidemiologic characteristics of preterm delivery: etiologic heterogeneity.
AB  - Preterm delivery (less than 37 weeks completed gestation) is known to result from
      diverse etiologic pathways, which can be grouped into idiopathic preterm labor,
      preterm premature rupture of the membranes, and medical complications. Data from
      publications providing sufficient detail to subdivide preterm delivery cases into
      these groups were tabulated. In spite of inconsistent terminology and incomplete
      reporting, patterns were identified. Black women have a markedly higher risk of
      preterm delivery, which is especially pronounced for preterm premature rupture of
      the membranes. Idiopathic preterm labor is predominant in lower-risk, white
      populations. These observations encourage consideration of subcategories of
      preterm delivery in studies of etiology and prevention.

PMID- 1992686
TI  - Menstrual mythology and sources of information about menstruation.
AB  - Surveys suggest that, despite extensive scientific knowledge of the biologic
      rhythms and physical changes associated with reproduction and despite the
      availability of excellent educational material about sexuality including
      menstruation, young peoples' knowledge of reproductive physiology is inadequate.
      Superstitions, illogical beliefs, and misinterpretations are more common than
      accurate understanding. The present article reviews menstrual mythology and
      describes sources of information for young people. Family and specialist
      physicians as well as educators in school or in the community need to recognize
      the limitations of the present methods of sexuality education, must realize that
      understanding of reproductive processes may be very incomplete, and should be
      prepared to work cooperatively with informal sources of information (peers,
      parents, and commercial companies). In addition, menstrual education needs to
      move away from the focus on hygienic management to that of healthy sexuality and
      acceptance of self.

PMID- 1992687
TI  - Inhibition of pulmonary surfactant function by meconium.
AB  - The pathophysiology of meconium aspiration is marked by lung hyperinflation
      because of airway obstruction, which is often followed by an acute pneumonitis
      with classic lung injury characteristics. Surfactant dysfunction may contribute
      to this latter pulmonary pathophysiology. We sought to determine to what extent
      meconium itself might contribute to a functional surfactant deficiency. Specimens
      of newborn infants' first meconium were collected and pooled. Serial dilutions of
      the meconium were then added to various concentrations of calf lung surfactant
      extract, a mixture with the surface properties of natural surfactant that is used
      clinically to treat neonatal respiratory distress syndrome, and the dynamic
      surface activity of these mixtures was studied with a pulsating bubble
      surfactometer. At surfactant concentrations of less than or equal to 1.5 mg/ml,
      even 6500-fold dilutions of meconium-inhibited surface tension lowering ability
      (10 +/- 2 mN/m vs 1 +/- 0.1 mN/m for controls, p less than 0.05). Moreover, this
      inhibitory activity resided in both the chloroform-soluble and the aqueous phases
      of meconium and appeared to be additive in nature. However, at sufficiently high
      concentrations of surfactant, even large amounts of meconium were unable to
      affect surface tension lowering properties. Thus meconium inhibits surfactant
      function in a manner that is dependent on the surfactant concentration,
      suggesting the possible utility of exogenous surfactant therapy in some cases of
      meconium aspiration.

PMID- 1992688
TI  - The effects of iodoprophylaxis on thyroid size during pregnancy.
AB  - Thyroid gland size was ultrasonographically determined in 35 pregnant women who
      live in an area with moderate iodine deficiency. Iodide salt was administered to
      group A (n = 17), whereas group B (n = 18) was used as a control. Each group was
      tested for thyroid-stimulating hormone serum levels, iodine excretion, and
      thyroid volume. In both groups thyroid-stimulating hormone levels were similar
      and did not change throughout pregnancy. The iodine excretion at the third
      trimester in the treated group was significantly (p less than 0.01) higher than
      that of group B (100.0 +/- 39.0 versus 50.0 +/- 37.0 micrograms iodine per 24
      hours, respectively). Initially, thyroid volume did not differ between the two
      groups. At the end of pregnancy, no difference was found in thyroid size in group
      A, whereas in the untreated women it increased significantly (p less than 0.0001)
      with a mean increase of 1.6 +/- 0.6 ml (16.2% +/- 6.0%). These results show that
      the increased thyroid size in the control group was mainly a result of relative
      iodine deficiency and that iodoprophylaxis should be warranted even in areas with
      moderate iodine deficiency to prevent the increase in thyroid size and, probably,
      to avoid the risk of maternal and fetal hypothyroidism.

PMID- 1992689
TI  - Investigation of placental circulations by color Doppler ultrasonography.
AB  - The placental circulations of 25 normal and five complicated pregnancies were
      studied by color Doppler ultrasonography. Flow velocity waveforms were obtained
      in all 30 pregnancies and could discriminate between fetal and maternal
      intraplacental blood flow. We believe that color Doppler ultrasonography will
      improve our understanding of the pathophysiology of various pregnancy disorders
      that alter the placental circulations and that color ultrasonography is useful
      for the prenatal differential diagnosis of intrauterine masses.

PMID- 1992690
TI  - Reduction of cardiovascular disease-related mortality among postmenopausal women
      who use hormones: evidence from a national cohort.
AB  - A national sample of 1944 white menopausal women greater than or equal to 55
      years old from the epidemiologic follow-up of participants in the National Health
      and Nutrition Examination Survey was reviewed to investigate the role of hormone
      therapy in altering the risk of death from cardiovascular disease. Women in the
      study were observed for up to 16 years after the baseline survey in 1971 to 1975.
      By 1987 631 women had died; 347 of these deaths were due to cardiovascular
      disease. History of diabetes (relative risk, 2.38; 95% confidence interval 1.73
      to 3.26), previous myocardial infarction (relative risk, 2.12; 95% confidence
      interval 1.56 to 2.86), smoking (relative risk, 2.18; 95% confidence interval,
      1.69 to 2.81), and elevated blood pressure (relative risk, 1.49; 95% confidence
      interval, 1.14 to 1.94) were strong predictors of cardiovascular disease-related
      death in this cohort. After adjusting for known cardiovascular disease risk
      factors (smoking, cholesterol, body mass index, blood pressure, previous
      myocardial infarction, history of diabetes, age) and education, the use of
      postmenopausal hormones was associated with a reduced risk of death from
      cardiovascular disease (relative risk, 0.66; 95% confidence interval, 0.48 to
      0.90). The same protective effect provided by postmenopausal hormone therapy was
      seen in women who experienced natural menopause (relative risk, 0.69; 95%
      confidence interval, 0.45 to 1.06).

PMID- 1992691
TI  - Endosalpingosis as a cause of chronic pelvic pain.
AB  - Endosalpingosis, a condition characterized by ectopic oviduct epithelium, is
      diagnosed histologically by the appearance of benign ciliated and nonciliated
      columnar cells in an abnormal location. Endosalpingosis is typically without
      symptoms. Our unusual case report shows symptomatic endosalpingosis first seen
      with chronic pelvic pain. Various aspects of this disease will also be discussed.

PMID- 1992692
TI  - Transvaginal ultrasonographic definition of the central nervous system in the
      first and early second trimesters.
AB  - A 6.5 MHz transvaginal sector scanner was used to describe the fetal central
      nervous system anatomy from 6 to 14 weeks. One hundred thirty-three pregnant
      patients were scanned after the crown-rump measurements were found to be within a
      range of less than or equal to 4 days from menstrual age. The number of possible
      ultrasonographic sections ("slices"), as well as the number of successful views
      in the axial, coronal, and sagittal sections, was tabulated. A detailed list of
      central nervous system structures that are seen at each gestational age is
      presented. The results showed that a significant number of brain structures could
      be imaged. The number and the clarity of the structures and the number of
      successful views in the three scanning planes increased with gestational age. We
      concluded that transvaginal scanning for central nervous system maldevelopment
      can be started in the late first and early second trimesters.

PMID- 1992694
TI  - Prenatal records: a national survey of content.
AB  - The uses of prenatal records extend well beyond management of patient care. They
      are also vehicles for communication, quality assurance, financial compensation,
      and legal documentation. To serve each of these functions, records should be
      systematic and detailed. This nationwide study was conducted to assess the extent
      to which prenatal records in current use include sufficient detail to serve these
      functions. A random sample of 2746 physicians who listed obstetrics and
      gynecology, obstetrics, or maternal-fetal medicine as a primary or secondary
      specialty in the American Medical Association file were contacted by mail and
      were requested to submit a blank copy of their prenatal records. The records of
      969 respondents were examined for the presence or absence of 53 items that
      corresponded to the five functions identified above. The items of interest were
      present in 1% to 98% of the records. More than 90% included items of traditional
      medical-obstetric significance. The percentages of records with items of more
      contemporary relevance (e.g., cigarette smoking, risk-assessment checklists,
      psychological stress) were found in lower percentages of the records. Stratified
      and logistic regression analyses revealed that the most systematic and detailed
      records were commercially available, were used by physicians in hospital and
      government program-based practices, and were used by physicians who had completed
      medical school less than or equal to 15 years before the survey. The findings
      suggest that physicians who do not use commercially available forms or those who
      are in private or health maintenance organization practice or have been
      practicing for more than 15 years should reconsider their prenatal records in
      light of the functions they will serve in the 1990s and beyond.

PMID- 1992693
TI  - Endothelial-derived relaxing factor released by endothelial cells of human
      umbilical vessels and its impairment in pregnancy-induced hypertension.
AB  - The principal objective of this study was to determine and compare the capability
      of human umbilical vessels of normal and pregnancy-induced hypertensive
      parturients to produce and to release the endothelial-derived relaxing factor. A
      bolus of bradykinin injected in the perfusion system of human umbilical vessels
      induces a release of a relaxant factor, detectable by bioassay, that is
      pharmacologically similar to the endothelial-derived relaxing factor. Human
      umbilical cords were collected from normal and pregnancy-induced hypertensive
      parturients. In the latter group the release of endothelial-derived relaxing
      factor is extremely reduced. In fact, in umbilical vessels collected from normal
      parturients, bradykinin at a dose of 20 pmol produces a release of endothelial
      derived relaxing factor equivalent to a relaxation induced by 59.9 +/- 11.0 and
      30.8 +/- 11.4 pmol of glyceryl trinitrate for the artery and vein, respectively.
      The same dose of bradykinin in umbilical vessels, collected from pregnancy
      induced hypertensive parturients, produces a release equivalent to 6.6 +/- 2.2
      and 5.7 +/- 3.5 pmol of glyceryl trinitrate equivalent for the artery and vein,
      respectively. Neither an increasing bolus of exogenous bradykinin or an infusion
      of superoxide dismutase or L-arginine was able to restore the production of
      endothelial-derived relaxing factor to normal levels. Our results indicate a
      probable alteration of endothelial cell numbers or an alteration of the enzymatic
      pathway, probably due to cytotoxic endogenous factors produced in pregnancy.

PMID- 1992695
TI  - Reproductive factors and risk of endometrial cancer.
AB  - The role of reproductive factors in endometrial cancer risk has been analyzed in
      a case-control study conducted since 1983 in the greater Milan area on 568 women
      (cases) with histologically confirmed endometrial cancer and 1925 women
      (controls) who were admitted for acute, nonmalignant, hormonal, gynecologic
      conditions to hospitals that cover a comparable catchment area. Compared with
      nulliparous women, parous women had a 30% lower risk of endometrial cancer, but
      there was no evidence of a decline in risk with increasing number of births. The
      risk of the disease decreased with number of spontaneous or induced abortions;
      the multivariate relative risk estimates were, compared respectively with no
      spontaneous or induced abortions, 0.5 for women with two or more spontaneous
      abortions and 0.3 for women with two or more induced abortions; both trends in
      risk were statistically significant. When parous women only were considered, no
      association emerged between endometrial cancer and age at first birth, but the
      risk decreased with increasing age at last birth: compared with women whose last
      birth occurred before age 25, the relative risk was 0.5 for women who were
      greater than or equal to 35 years old at last birth, and the multivariate trend
      in risk was statistically significant. For most of the reproductive factors that
      were considered, the risk estimates tended to be greater at younger age or among
      premenopausal women and to flatten off in subsequent strata of age. An
      association between endometrial cancer and age at first birth was observed in
      women who were less than or equal to 49 years old, but not in older groups. The
      observation that later age at last birth as well as later first birth in younger
      women decreases the risk of endometrial cancer suggests a short-term protective
      effect of pregnancy. This finding is consistent with a late-stage (promotional)
      effect of reproductive factors on endometrial carcinogenesis.

PMID- 1992696
TI  - Cervical findings in rape victims.
AB  - The difficulty of documenting genital findings in rape victims by gross
      visualization is well known. However, we report two cases in which cervical
      findings were readily established by colposcopic examination and photography. Use
      of the colposcope may significantly increase the reliability of establishing
      findings in rape victims.

PMID- 1992697
TI  - Continuous electrocardiographic monitoring in hypertensive crises in pregnancy.
AB  - Twenty-four patients first seen with hypertensive crises during pregnancy were
      studied by continuous electrocardiographic monitoring for a period of 24 hours to
      detect the presence of serious ventricular arrhythmias. Three patients were
      excluded from analysis because of low serum potassium levels. Thirteen of the
      remaining 21 patients had ventricular tachycardia on subsequent analysis of the
      electrocardiogram. These arrhythmias subsided after induction of anesthesia when
      blood pressure control was optimal. This finding may be implicated in the
      pathogenesis of pulmonary edema and sudden death in these patients.

PMID- 1992698
TI  - Umbilical artery blood flow velocity waveforms during variable deceleration of
      the fetal heart rate.
AB  - Blood flow velocities of the umbilical arteries were measured by Doppler
      ultrasonography during variable decelerations of the fetal heart rate. The flow
      velocity waveforms, being normal between uterine contractions, showed either an
      unchanged flow velocity waveform with an exclusive fetal heart rate effect on end
      diastolic velocities or a rapid change to absent and reverse diastolic flow
      during the decelerations, indicating an abrupt increase in placental resistance
      with a halt in placental perfusion. Computer-aided reconstruction of the fetal
      heart rate curve revealed the exact temporal relationship between the reduction
      of umbilical artery perfusion and deceleration of fetal heart rate. We showed
      that variable decelerations of fetal heart rate can be observed during only
      slightly changed umbilical perfusion or can be caused by a halt in placental
      perfusion, which does not necessarily mean an absence of any movement of the
      fetal blood column, but is a result of a systolic forward and diastolic reverse
      flow to the same extent.

PMID- 1992699
TI  - A case report of giant cell arteritis of the uterus and adnexa.
AB  - Giant cell arteritis of the uterus and adnexa is a rare disorder, which is
      generally asymptomatic and occasionally associated with temporal arteritis. The
      true clinical significance of this dramatic microscopic finding remains obscure,
      but arteritis of the uterus and adnexa may be associated with later development
      of giant cell arteritis elsewhere in the body.

PMID- 1992700
TI  - Prospective analysis of sperm-oocyte fusion and reactive oxygen species
      generation as criteria for the diagnosis of infertility.
AB  - We have undertaken a prospective analysis of the diagnostic significance of three
      different criteria of human sperm function including the conventional semen
      profile, measurements of hamster-oocyte fusion, and determinations of reactive
      oxygen species generation in 139 couples. The latter, who were characterized by a
      lack of detectable abnormalities in the female partner, were followed up for a
      maximum of 4 years to determine the incidence of spontaneous pregnancy in the
      absence of therapeutic intervention. Assessments of monthly fecundity with life
      table analysis techniques revealed a highly significant, positive relationship
      between fertility and hamster-oocyte fusion rates that were measured in the
      presence of the ionophore, A23187. Conversely, reactive oxygen species generation
      was shown to be negatively associated with both the outcome of the sperm-oocyte
      fusion assay and fertility in vivo. The clinical significance of these diagnostic
      techniques was emphasized by the fact that within the same data set, the
      conventional semen profile was of no significant diagnostic value.

PMID- 1992701
TI  - Vasoactive intestinal polypeptide loses its ability to increase vaginal blood
      flow after menopause.
AB  - The effect of vasoactive intestinal polypeptide on vaginal blood flow was
      investigated in postmenopausal women. In women who were receiving hormonal
      replacement therapy the vasodilatory response induced by vasoactive intestinal
      polypeptide was identical to that of young women, whereas in postmenopausal women
      who were receiving no replacement therapy, the response induced by vasoactive
      intestinal polypeptide was absent. Plasma levels of vasoactive intestinal
      polypeptide and systemic cardiovascular effects were identical in the two groups.

PMID- 1992702
TI  - Reproducibility of the oral glucose tolerance test in pregnancy.
AB  - This prospective investigation evaluated the reproducibility of the 100 gm oral
      glucose tolerance test. Sixty-four obstetric patients with greater than or equal
      to 135 mg/dl on the 50 gm oral glucose screening test were scheduled for the 100
      gm test. All patients repeated the oral glucose tolerance test in 1 to 2 weeks.
      Both tests included a preparatory diet, and testing conditions were identical.
      There were no significant differences in the mean test values at each testing
      interval when the entire study population was considered. Patients were then
      divided into four groups according to the outcome of the two tests. Forty-eight
      of 64 (75%) had normal results at each testing period (group 1); 11 of 64 (17%)
      had initially normal results and abnormal results on retest (group 2); 3 of 64
      (5%) had initially abnormal results and normal results on retest (group 3); 2 of
      64 (3%) had abnormal results at both testing phases (group 4). There were no
      significant differences between oral glucose tolerance test results within groups
      1 and 4. However, significant differences occurred within groups 2 and 3 between
      the two tests. Group 2 patients had a greater frequency of an abnormal 1-hour
      value on the test than group 1 patients (p = 0.001). Overall, the reproducibility
      of the oral glucose tolerance test was 78% (50 of 64). We recommend the oral
      glucose tolerance test be repeated when the 1-hour value is abnormal or when the
      fasting blood sugar, 1-hour, and 2-hour values are near the upper end of the
      normal range.

PMID- 1992703
TI  - Steroid-responsive nephrotic syndrome with renal insufficiency in the first
      trimester of pregnancy.

PMID- 1992704
TI  - Ovarian neoplasms and the risk of adnexal torsion.
AB  - Previous reports examining adnexal torsion suggested that benign ovarian
      neoplasms are more likely to undergo torsion than malignant ovarian neoplasms. To
      our knowledge, this clinical observation has not been quantified. To examine this
      hypothesis, we reviewed our experience with ovarian neoplasms found at the time
      of surgery over a 10-year period. Benign ovarian neoplasms had a 12.9-fold
      increased risk of undergoing adnexal torsion when compared with malignant ovarian
      neoplasms (95% confidence interval, 10.2 to 15.9). The histologic type of ovarian
      neoplasm does not appear to affect the rate of adnexal torsion. Adnexal torsion
      rarely involves cancer.

PMID- 1992705
TI  - Umbilical cord ulceration and intestinal atresia: a new association?
AB  - In three fetuses, congenital intestinal atresia was associated with linear
      ulcerations of the umbilical cord. In two cases, hemorrhage was seen from the
      cord ulcer. Both fetuses required emergency cesarean section for fetal distress
      and were born anemic. The third fetus was mildly hydropic, attributed to
      hemorrhage, and was stillborn. The mechanism of the association could not be
      determined. These cases suggest a risk of prenatal umbilical cord hemorrhage in
      infants with intestinal atresia.

PMID- 1992706
TI  - Mechanisms of hemolysis and anemia associated with acute antepartum
      pyelonephritis.
AB  - Anemia develops in about a fourth of women whose pregnancy is complicated by
      pyelonephritis, although its exact mechanism has not been defined clearly. In
      this study of 18 women with antepartum pyelonephritis, although only a third had
      anemia (hematocrit less than 30 vol/dl), there was evidence for hemolysis in all
      18. Specifically there was a mean decrease in hematocrit of 5 vol/dl from
      admission to discharge. With scanning electron microscopy, we compared
      erythrocyte morphologic aberrations that were found in women with renal infection
      with those of normally pregnant women, and the former had significantly increased
      proportions of echinocytes in particular, but schistocytes and spherocytes were
      increased also (total 10.3% vs 1.4%, p less than 0.0001). These changes,
      especially echinocytosis, have been induced in vitro by lipopolysaccharide, and
      they are known to lead to premature red blood cell destruction in vivo. We
      conclude that hemolysis with subsequent anemia in pregnant women with
      pyelonephritis is caused by lipopolysaccharide-induced red blood cell membrane
      damage.

PMID- 1992707
TI  - Fetal panting: yet another response to the external vibratory acoustic
      stimulation test.
AB  - Fetal panting at a rate of 119 respiratory movements per minute, persisting for
      40 minutes after external vibratory acoustic stimulation, was noted in a fetus at
      33 weeks' gestation. Subsequent fetal outcome was good. The possible underlying
      pathophysiologic mechanism is discussed.

PMID- 1992708
TI  - The increased frequency of cervical dysplasia-neoplasia in women infected with
      the human immunodeficiency virus is related to the degree of immunosuppression.
AB  - Cytologic and histologic investigations of the uterine cervix and studies of the
      lymphocyte functions were performed in human immunodeficiency virus-infected and
      human immunodeficiency virus antibody-negative women to study possible linkages
      between human papillomavirus-induced dysplasia and degree of human
      immunodeficiency virus-induced immunosuppression. Cytologic smears of the uterine
      cervix of 111 human immunodeficiency virus-infected women were compared with
      findings in 76 female intravenous drug users negative for human immunodeficiency
      virus antibodies and in a group of 526 women of the outpatient population of the
      hospital. Cervical dysplasia-neoplasia (including five cases of invasive
      carcinoma) was seen in 41% of the human immunodeficiency virus-infected patients.
      In human immunodeficiency virus-negative intravenous drug users dysplasia
      neoplasia was seen in 9%, and in the sample from outpatients in 4%, including two
      cases of invasive carcinoma (p less than 0.01). Cytologic features that were
      attributable to infection with human papillomavirus were observed in human
      immunodeficiency virus-infected women four times more often than in the sample
      from the outpatient population (p less than 0.01). Frequency and severity of
      dysplasia appear to increase with diminishing numbers of CD4+ helper/inducer T
      lymphocytes and correlated significantly (p less than 0.01) with a loss of
      blastogenic response to phytohemagglutinin, pokeweed mitogen, and tetanus toxoid.
      These results suggest an increased risk for the development of dysplasia of the
      uterine cervix in women with human immunodeficiency virus infection, which is
      related to the degree of immunosuppression.

PMID- 1992709
TI  - Characterization of enzymes of catecholamine synthesis and metabolism in human
      fetal membranes at birth.
AB  - We looked for the presence of the enzymes monoamine oxidase, catechol-O
      methyltransferase, and phenylethanolamine-N-methyltransferase in human fetal
      membranes at term. The activity of all three enzymes was detected via highly
      sensitive and selective radiometric enzyme assays. The most novel finding was the
      extremely high level of monoamine oxidase activity in the chorion compared with
      that in the amnion. The other enzyme of catecholamine metabolism, catechol-O
      methyltransferase, did not show any difference in activity between the two
      layers. In addition, we observed that the enzyme phenylethanolamine-N
      methyltransferase, which is primarily located in the adrenal medulla, was also
      present in appreciable levels in the two layers of fetal membranes. These results
      suggest that fetal membranes, like the placenta, possess the enzymatic machinery
      to metabolize catecholamines and have the capacity to synthesize epinephrine.

PMID- 1992710
TI  - Pregnancy-related mortality in New York City, 1980 to 1984: causes of death and
      associated risk factors.
AB  - To identify causes and risk factors for pregnancy-related mortality in New York
      City, we analyzed 224 pregnancy-related deaths that occurred from 1980 to 1984.
      The leading causes of death were ectopic pregnancy complications, embolism,
      intrapartum cardiac arrest, and hypertension. Mortality ratios were determined by
      comparing the characteristics of the women whose death was pregnancy-related with
      those of women who had survived delivery of a live infant in New York City during
      the same period. Black and Hispanic women had mortality ratios that were
      respectively 4.2 and 2.0 times higher than those for white, non-Hispanic women.
      In comparison with women aged 20 to 24, those older than 30 were more than twice
      as likely to die from pregnancy-related causes, and those older than 40 were five
      times as likely to do so. Other factors that were associated with an increased
      risk of pregnancy-related mortality included 9 to 11 years of education, lack of
      private medical insurance, more than five previous pregnancies, and fewer than
      five prenatal visits. This study suggests that changes in current maternal-health
      and family-planning services will be required to achieve further reductions in
      preventable pregnancy-related mortality.

PMID- 1992711
TI  - Estrogen receptors in the external anal sphincter.
AB  - Inasmuch as anal competence in women is reduced after the age of 50 years, it may
      be dependent on effects of estrogens. In this study, samples of the external anal
      sphincter were analyzed for the presence of estrogen receptors and were found to
      be present at a median concentration of 5.0 fmol per milligram of protein (range,
      1.9 to 13) in women (n = 7), and 1.1 fmol per milligram of protein (range, 0 to
      3.2) in men (n = 7). These findings are of interest with regard to the treatment
      of idiopathic anal incontinence.

PMID- 1992712
TI  - Transient postpartum diabetes insipidus.
AB  - Diabetes insipidus may first present before, during, or immediately after
      pregnancy. The characteristics of two unusual cases of transient postpartum
      diabetes insipidus are described and discussed.

PMID- 1992713
TI  - Postterm infants: too big or too small?
AB  - Concern over the postterm pregnancy has shifted from that of the difficult
      delivery of an excessively large fetus to the current concern with death in utero
      of an undernourished, small-for-date fetus. Studies of postterm pregnancy before
      the availability of ultrasonography may have included a large proportion of
      erroneous menstrual dates. The present study of 7000 infants was undertaken to
      reassess fetal growth in postterm pregnancies in which the expected date of
      confinement from last normal menstrual period dating was confirmed (+/- 7 days)
      by early ultrasonography. Results show a gradual shift toward higher birth weight
      and greater crown-heel length and head circumference between 273 and 300 days of
      gestational age. No evidence of postterm weight loss or lower weight for length
      could be demonstrated. Concern in postterm pregnancy should be for fetal
      macrosomia, not for intrauterine growth retardation.

PMID- 1992714
TI  - The biologic and social consequences of perinatal cocaine use in an inner-city
      population: results of an anonymous cross-sectional study.
AB  - Cocaine use among pregnant women and reports of its adverse perinatal
      consequences have increased substantially over the past 10 years. However, most
      researchers have studied patients registered at drug treatment centers or have
      relied on voluntary participation by patients, either of which introduces the
      possibility of selection bias. To determine the frequency and consequences of
      prenatal cocaine use among an unselected inner-city obstetric population, we
      collected urine samples from parturient women at a municipal hospital and
      anonymously tested these specimens for metabolites of cocaine, marijuana,
      opiates, and methadone. Urine specimens, with linked obstetric data sheets, were
      available from a study population of 1111 patients, and pediatric data sheets
      were available for 846 mother-infant pairs. Cocaine metabolites were found in
      11.5% of the urine samples collected, whereas metabolites of marijuana, opiates,
      and methadone, respectively, were present in 1.1%, 1.2%, and 0.3% of the
      specimens. Cocaine users were more likely than nonusers to have had no prenatal
      care (51% vs 8.8%; p less than 0.0001), to be American-born rather than Caribbean
      born (71% vs 33%; p less than 0.001), and to have a higher parity (1.83 vs 1.14;
      p less than 0.0001). Infants of cocaine users had a lower mean gestational age (
      0.93 weeks; p less than 0.01), a lower mean birth weight (2560 +/- 788 vs 3151 +/
      699 gm; p less than 0.001), and an increased probability of having an Apgar
      score of less than 7 at 5 minutes (12.5% vs 3.2%; p less than 0.0001). Multiple
      linear regression analysis that isolated confounding variables such as the
      presence or absence of prenatal care, maternal age and parity, and the use of
      cigarettes and alcohol did not substantially affect the differences described
      above. The effect of cigarette smoking on reducing fetal size was cumulative. In
      conclusion, cocaine is the most commonly used illicit drug among parturients in
      this community and is strongly associated with underutilization of prenatal care
      services. Infants of cocaine users are more likely to be preterm and depressed at
      birth and to have a low birth weight. Cocaine use, through the above-noted
      effects, increases the need for prenatal care while simultaneously decreasing the
      likelihood that it will be obtained.

PMID- 1992715
TI  - The value of squamous cell carcinoma antigen in patients with locally advanced
      cervical cancer undergoing neoadjuvant chemotherapy.
AB  - Serum levels of squamous cell carcinoma antigen were measured in 688 samples from
      119 patients with cervical cancer. Ninety-seven patients had primary tumors and
      22 had recurrent disease. Serum samples were obtained before each cycle of
      chemotherapy, before surgery, at least 4 weeks after surgery, and at 2- to 3
      month intervals during follow-up from 78 of the patients with locally advanced
      cervical cancer who were receiving neoadjuvant chemotherapy. Squamous cell
      carcinoma antigen serum levels were elevated (greater than 2.5 ng/ml) in 71% of
      the patients with primary tumors and in 77% of the patients with recurrent
      carcinomas. The percentage of positivity increased significantly with stage (p =
      0.03) and was higher in squamous cell tumors than in adenocarcinomas (p less than
      0.001). Pretreatment squamous cell carcinoma antigen levels were not predictive
      of neoadjuvant chemotherapy response; however, the serial measurement during
      chemotherapy showed a good correlation with clinical response. In the patients
      who had surgery, squamous cell carcinoma antigen positivity did not correlate to
      pathologic findings (lymph node status, cervical and parametrial infiltration).
      Disease-free survival was significantly longer in patients with squamous cell
      carcinoma antigen pretreatment values that were lower than 5 ng/ml, compared with
      patients with marker higher than 5 ng/ml (p less than 0.01). Abnormal squamous
      cell carcinoma antigen serum levels preceded the clinical detection of recurrence
      in eight of 11 patients with a median lead time of 5 months.

PMID- 1992716
TI  - Neonatal complications at term as related to the degree of umbilical artery
      acidemia.
AB  - The degree of umbilical arterial acidemia associated with immediate newborn
      morbidity has not been determined. Therefore we compared 358 term infants with
      umbilical artery acidemia (pH less than 7.20) with 358 term, nonacidotic matched
      control infants, to evaluate immediate neonatal complications in both groups.
      Nonacidotic was defined as an umbilical artery pH greater than or equal to 7.20.
      Complications included seizures, persistent hypotonia, and/or signs of end-organ
      damage such as renal or cardiac dysfunction. None of the 693 newborns with an
      umbilical artery pH greater than or equal to 7.00 had such complications. Two of
      23 infants with an umbilical artery pH less than 7.00 had sequelae related to
      intrapartum asphyxia. In these two infants the umbilical artery pH was less than
      7.00, the 1-minute and 5-minute Apgar scores were less than or equal to 3 and the
      acidemia was metabolic in nature.

PMID- 1992717
TI  - Urinary tract dilatation in pregnancy.
AB  - Right-sided ureteral and renal pelvis dilatation was observed during routine
      uterine ultrasonographic examination at 30 weeks' gestation. This continued to
      progress with the renal pelvis measuring 8.9 cm in diameter at 35 weeks, leading
      to early delivery. Renal function remained normal and these changes resolved
      completely after delivery.

PMID- 1992718
TI  - Clinical implications of screening for cervical cancer under Medicare. The
      natural history of cervical cancer in the elderly: what do we know? What do we
      need to know?
AB  - Despite the recent passage of coverage for Papanicolaou test screening under
      Medicare, several aspects of the natural history of cervical cancer in the
      elderly remain uncertain. This article reviews what we know about cervical cancer
      in elderly women to provide clinicians with the background necessary for
      assessments of screening recommendations, integration of new data into practice,
      and development of consensus approaches to screening in the elderly. Two central
      questions that affect a screening program for the elderly are how long the
      neoplastic process takes from preinvasive disease to the development of invasive
      cancer, and how likely is it that a given neoplastic state observed in an elderly
      woman will, in fact, progress to a more severe state. The ultimate success of the
      new Medicare benefit will also be affected by the use of Papanicolaou testing,
      the technique of obtaining the smear, and the adequacy of reporting and follow
      up. The expansion of Medicare benefits to include early cervical cancer detection
      has the potential to improve the quality and the duration of older women's lives.

PMID- 1992719
TI  - Toxicities in rats with free versus liposomal encapsulated cisplatin.
AB  - Wistar rats (five in each group) were given either 1 mg/kg of free cisplatin, 1
      or 2 mg/kg of liposomal encapsulated cisplatin, or saline solution
      intraperitoneally biweekly for 15 injections. Rats in the free drug group showed
      significantly less weight gain; two rats died during the study. At necropsy, the
      free cisplatin--treated rats showed gross and microscopic evidence of peritoneal
      fibrosis that was not detected in any of the remaining groups. The free cisplatin
      -treated rats showed serum and histologic evidence of renal damage; all five rats
      had moderate or severe acute tubular necrosis. No renal abnormalities were
      detected in rats that received 1 mg/kg, and only focal or mild changes were found
      in rats that received 2 mg/kg of the liposomal preparation. Neurotoxicity, as
      determined by nerve conduction and inclined plane studies, developed in rats
      treated with free and liposomal cisplatin. These results are encouraging and
      warrant further investigation.

PMID- 1992720
TI  - Epidermal growth factor receptor expression in normal ovarian epithelium and
      ovarian cancer. I. Correlation of receptor expression with prognostic factors in
      patients with ovarian cancer.
AB  - Previous studies in breast and bladder cancer have suggested that epidermal
      growth factor receptor is expressed by only a proportion of cancers and is
      associated with poor clinical outcome. We used a monoclonal antibody specifically
      reactive with the extracellular domain of the epidermal growth factor receptor to
      localize this receptor immunohistochemically in frozen sections of normal ovary
      and epithelial ovarian cancer. Normal ovarian epithelium was found to express
      epidermal growth factor receptor in all cases. Among 87 ovarian cancers, however,
      23% did not express immunohistochemically detectable receptor. Epidermal growth
      factor receptor expression was not related to histologic grade or stage, but was
      associated with poor survival (p less than 0.05). The median length of survival
      of patients with tumors that did not express epidermal growth factor receptor was
      40 months compared with 26 months in patients with tumors that did express
      epidermal growth factor receptor. As in breast and bladder cancer, expression of
      epidermal growth factor receptor in ovarian cancer appears to be a poor
      prognostic factor.

PMID- 1992721
TI  - Dose effects of antenatal corticosteroids for induction of lung maturation in
      preterm rabbits.
AB  - Dose-response effects of corticosteroids were investigated in the preterm rabbit.
      Pregnant rabbits were given two doses of 0.01, 0.03, or 0.1 mg of betamethasone
      per kilogram every 24 hours, beginning on day 25 of gestation. Saline solution
      was used in a comparison treatment group. Half of the newborn rabbits received
      supplemental surfactant therapy after delivery via cesarean section on day 27,
      and all were ventilated on a ventilator-plethysmograph system for 30 minutes. The
      0.01 and 0.03 mg/kg regimens had no effect on birth weight or lung function. The
      0.1 mg/kg regimen resulted in fetal growth retardation and improved ventilatory
      measurements, gas exchange, and decreased protein accumulation in the lung,
      without increasing surfactant pool size. The induction of lung maturation by
      corticosteroids has multiple targets in the developing lung and does not exhibit
      a linear dose response.

PMID- 1992722
TI  - Phospholipase C activity in microorganisms associated with reproductive tract
      infection.
AB  - Phospholipase C (lecithinase or phosphatidylcholine phosphorylase) catalyzes the
      hydrolysis of lecithin into phosphorylcholine and 1,2-diglyceride. Bacterial
      production of phospholipase C may damage reproductive tract tissues by both
      direct and indirect mechanisms. Use of the synthetic substrate p
      nitrophenylphosphorylcholine phospholipase C activity was determined in 204
      isolates representative of those found in female genital tract. Multiple aerobic
      (28%) and anaerobic (28%) reproductive tract microorganisms showed phospholipase
      C activity. Phospholipase C-producing isolates included strains of Bacteroides
      fragilis, B. bivius, B. thetaiotaomicron, Gardnerella vaginalis, and group B
      streptococcus. Phospholipase C activity was heterogenous; not all isolates that
      belong to a particular species showed activity. Phospholipase C production may be
      a possible virulence factor produced by a number of microflora commonly
      implicated in various reproductive tract infections or conditions, as well as in
      some instances of preterm birth.

PMID- 1992724
TI  - Effect of subject height on the result for the fifty-gram oral glucose tolerance
      test.

PMID- 1992723
TI  - Effects of acute hypermagnesemia on the threshold for lidocaine-induced seizures
      in the rat.
AB  - The effects of acute changes in plasma magnesium concentration on the threshold
      for lidocaine-induced seizures were evaluated in mechanically ventilated rats
      receiving 70% nitrous oxide and 30% oxygen. In experiment 1, male rats were
      intravenously administered either 0.9% sodium chloride (group I) or 5.0%
      magnesium sulfate to elevate plasma magnesium levels to 5.8 +/- 0.1 (group II) or
      10.5 +/- 1.0 mg/dl (group III). In experiment 2, pregnant rats were intravenously
      administered either 0.9% sodium chloride (normomagnesemia) or magnesium sulfate,
      resulting in a plasma magnesium concentration of 7.8 +/- 1.4 mg/dl. Thirty
      minutes later, a continuous intravenous infusion of lidocaine (2.3 mg/kg per
      minute) was begun in both experiments. Biparietal electroencephalographic
      activity was monitored continuously. At the onset of electroencephalographic
      seizure activity, arterial plasma magnesium and lidocaine concentrations were
      measured. In groups I and III (experiment 1), brain parenchymal magnesium was
      also assayed. There were no differences in plasma lidocaine concentrations (in
      experiments 1 or 2) between saline solution and hypermagnesemic groups at onset
      of seizures. Brain magnesium level was unaltered by magnesium sulfate infusion.
      We conclude that acute administration of magnesium sulfate alters neither brain
      magnesium level nor the plasma lidocaine concentration associated with onset of
      electroencephalographic seizures.

PMID- 1992725
TI  - Methotrexate treatment of ectopic gestation and reproductive outcome.

PMID- 1992726
TI  - Predictive value: symptoms of preterm labor.

PMID- 1992727
TI  - Successful treatment of postpartum shock caused by amniotic fluid embolism with
      cardiopulmonary bypass and pulmonary artery thromboembolectomy.

PMID- 1992728
TI  - Intraumbilical injection of oxytocin.

PMID- 1992729
TI  - Koch's postulates: revisited or revised?

PMID- 1992730
TI  - Frontothalamic measurement in the second trimester of pregnancy.

PMID- 1992731
TI  - Prevalence of acquired immunodeficiency syndrome detected during prenatal care of
      population of low socioeconomic status.

PMID- 1992732
TI  - A chill wind blows fresh air.

PMID- 1992733
TI  - Webster should not affect prenatal diagnosis.

PMID- 1992734
TI  - A comparison of penetrating keratoplasty to epikeratoplasty in the surgical
      management of keratoconus.
AB  - Of 40 patients intolerant to contact lenses, 47 eyes with keratoconus were
      surgically corrected with either epikeratoplasty (N = 31) or penetrating
      keratoplasty (N = 16). The percentage of eyes in both groups that had visual
      acuity of 20/40 or better with contact lenses at one year were equal (14 of 15
      eyes [93.3%] in the penetrating keratoplasty group; 27 of 29 eyes [93.1%] in the
      epikeratoplasty group); however, the penetrating keratoplasty procedure resulted
      in a higher percentage of eyes that had visual acuity of 20/20 than the
      epikeratoplasty group (11 of 15 eyes [73%] compared with seven of 29 eyes
      [24.1%], respectively). Both procedures resulted in significant corneal
      flattening, with the penetrating keratoplasty group producing an average of 3
      diopters more keratometric reduction than the epikeratoplasty group one year
      postoperatively. Although no irreversible graft failures occurred, five of 16
      eyes (31%) in the penetrating keratoplasty group had graft reactions. No serious
      complications were noted in the eyes of the epikeratoplasty group. Both
      procedures were effective in the surgical management of keratoconus.

PMID- 1992735
TI  - Posterior chamber intraocular lens implantation in eyes with inactive and active
      proliferative diabetic retinopathy.
AB  - We reviewed the records of 2,100 consecutive eyes that had undergone
      extracapsular cataract extraction with intraocular lens implantation between
      January 1981 and December 1989. Of these eyes, 21 had inactive and four had
      active proliferative diabetic retinopathy at the time of cataract extraction.
      Twenty-one eyes with inactive proliferative diabetic retinopathy received
      extracapsular cataract extraction with posterior chamber intraocular lens
      implantation, and four eyes with active proliferative diabetic retinopathy had
      both extracapsular cataract extraction with posterior chamber intraocular lens
      implantation and pars plana vitrectomy with endophotocoagulation. The mean follow
      up period was 27 months. Final visual acuity was 20/40 or better in 12 of 25 eyes
      (48%). Of 25 eyes, five (20%) showed progression of the retinopathy after the
      operation, and two (8%) developed macular edema. Extracapsular cataract
      extraction and posterior chamber intraocular lens implantation was well tolerated
      in most eyes.

PMID- 1992736
TI  - Delayed-onset pseudophakic endophthalmitis.
AB  - We reviewed 19 cases of delayed-onset pseudophakic endophthalmitis in which
      diagnostic cultures were performed at one month or more after cataract extraction
      with posterior chamber intraocular lens implantation. We isolated four different
      organisms in these 19 cases: 12 Propionibacterium species (63%), three Candida
      parapsilosis (16%), three Staphylococcus epidermidis (16%), and one
      Corynebacterium species (5%). Because of the unusual delayed-onset features of
      these cases and the retrospective nature of this study, a variety of treatment
      regimens were used. Twelve patients had recurrence of marked inflammation despite
      an apparent initial cure, and ten of these patients had positive culture results
      on repeat examination of intraocular fluids. Nine patients continued to be
      treated with topical corticosteroids postoperatively to suppress low-grade
      inflammation. Of the 19 patients, 16 had final visual acuity of 20/400 or better.
      Delayed-onset pseudophakic endophthalmitis had a more favorable visual prognosis,
      compared to acute-onset endophthalmitis.

PMID- 1992737
TI  - Extracapsular cataract extraction with intraocular lens implantation after
      scleral buckling surgery.
AB  - We reviewed the records of 28 patients who had undergone successful scleral
      buckling surgery followed by extracapsular cataract extraction with implantation
      of an intraocular lens. Posterior chamber intraocular lenses were inserted in 27
      eyes, and anterior chamber intraocular lenses were inserted in two eyes with
      posterior capsule rupture at the time of surgery. The mean follow-up period was
      44 months. Final visual acuity was 20/40 or better in 15 of 29 eyes (52%). One
      eye (3.4%) developed a recurrent retinal detachment 15 months after cataract
      surgery. Two eyes (6.9%) developed angiographically proven cystoid macular edema.
      The outcome for extracapsular cataract extraction with intraocular lens
      implantation in eyes that had previously undergone successful scleral buckling
      for retinal detachment is favorable.

PMID- 1992738
TI  - Quantitative analysis of lens changes after vitrectomy by fluorophotometry.
AB  - We measured the amount of autofluorescence in the lens to evaluate quantitatively
      lens changes after vitrectomy. Thirteen phakic patients, ranging in age from 12
      to 75 years, were studied after unilateral vitrectomy, with a follow-up period of
      more than two years (range, 26 to 55 months). Autofluorescence in the lens was
      measured at the center along the ocular axis by fluorophotometry. Lens
      autofluorescence in the eyes that underwent vitrectomy was significantly higher
      than in the contralateral eyes that were not operated on (P = .0003). The
      increase of autofluorescence was correlated significantly with the age at time of
      vitrectomy (P = .0008). There was no correlation between the increase in
      autofluorescence and the length of postoperative follow-up or the use of air
      during vitrectomy. Based on these results, we believe that oxidation of lens
      proteins intraoperatively may be one of the causes of development of nuclear
      cataract after vitrectomy.

PMID- 1992739
TI  - Control of intraocular pressure with apraclonidine hydrochloride after cataract
      extraction.
AB  - We conducted a randomly assigned, double-masked, controlled clinical trial to
      assess the efficacy of 1% apraclonidine hydrochloride in controlling
      postoperative intraocular pressure increases in patients undergoing extracapsular
      cataract extraction. Apraclonidine hydrochloride was given either one hour
      preoperatively or immediately after uncomplicated, extracapsular cataract
      extraction with posterior chamber intraocular lens implantation and compared with
      artificial tears given immediately postoperatively. Those who received
      apraclonidine hydrochloride preoperatively had significantly lower mean
      intraocular pressure at the first postoperative reading (P = .0005). After
      preoperative and postoperative apraclonidine hydrochloride, the mean early
      postoperative intraocular pressure was 19.8 mm Hg and 32.0 mm Hg, respectively,
      and 27.6 mm Hg after artificial tears. No patient who received preoperative
      apraclonidine hydrochloride had an intraocular pressure increase to 30 mm Hg or
      higher postoperatively. Nine of 20 patients (45%) who received postoperative
      apraclonidine hydrochloride and eight of 18 patients (44%) who received
      postoperative artificial tears had an increase of intraocular pressure to 30 mm
      Hg or higher in the early postoperative period. These differences were also
      highly significant (P = .0005).

PMID- 1992740
TI  - Comparison of a 3- and 6-mm incision in combined phacoemulsification and
      trabeculectomy.
AB  - We studied 216 eyes of 160 patients who underwent combined phacoemulsification
      and posterior chamber intraocular lens implantation with trabeculectomy. The mean
      follow-up was 18.7 months, with a minimum follow-up of six months. To assess the
      safety and efficacy of a recently developed 3-mm incision procedure with foldable
      intraocular lens implantation (phacotrabeculectomy), we compared 104 eyes
      subjected to this procedure with 112 eyes subjected to a 6-mm procedure at
      different follow-up periods. Intraocular pressure control (less than 21 mm Hg)
      was attained in 44 of 46 eyes (96%) in the 3-mm group and 71 of 76 eyes (93%) in
      the 6-mm group at one year postoperatively. Visual acuity of 20/40 or better was
      attained in 40 of 46 eyes (87%) in the 3-mm group and 66 of 76 eyes (87%) in the
      6-mm group. The incidence of postoperative complication was significantly lower
      (P less than .001) and visual acuity in the early postoperative period was
      significantly better (P less than .01) in the 3-mm incision group than in the
      comparison group.

PMID- 1992741
TI  - The prevalence of retinal vascular abnormalities in children and adolescents with
      essential hypertension.
AB  - We studied 97 children and adolescents with essential hypertension by evaluating
      photographs of the optic fundus and fluorescein angiography. Photographs were
      examined for the presence of arteriolar narrowing, tortuosity, and arteriovenous
      nicking. Intraobserver and interobserver variability in determination of
      abnormalities was low with agreement of 75% for narrowing, 90% for tortuosity,
      and 100% for arteriovenous nicking. The prevalence of abnormalities was 41% (95%
      confidence interval, 31% to 50%) for arteriolar narrowing, 14% (95% confidence
      interval, 19% to 21%) for tortuosity, and 8% (95% confidence interval, 5% to 11%)
      for arteriovenous nicking. Of 97 patients, 50 (51%) had one or more abnormality.
      Retinal abnormalities are relatively common in young patients with essential
      hypertension.

PMID- 1992742
TI  - Visual recovery in patients with optic neuritis and visual loss to no light
      perception.
AB  - We reviewed the records of 151 patients with optic neuritis examined over an
      eight-year period. Of these patients, 12 developed visual acuity of no light
      perception during the first episode of optic neuritis in the affected eye. Eight
      of the 12 patients recovered visual acuity of 20/40 or better. Of these, five
      patients had visual acuity of 20/20 or better, one had visual acuity of 20/25,
      one had visual acuity of 20/30, and one had visual acuity of 20/40. Four of the
      12 patients recovered peripheral visual fields but had dense central scotomas and
      visual acuity of less than 20/400. Dyschromatopsia persisted after visual
      recovery in 11 of 12 patients.

PMID- 1992743
TI  - Acetazolamide in the treatment of abnormal oculovestibular response.
AB  - We treated seven patients with incapacitating vertigo elicited by walking down a
      grocery store aisle or driving a car. Results of neurologic, neuro-ophthalmic,
      and neuroradiologic examinations were normal. Episodic vertigo secondary to an
      abnormal oculovestibular response was diagnosed. Each patient was given a trial
      of 250 to 500 mg of acetazolamide daily. Symptoms resolved completely in four
      patients, two patients had near resolution of symptoms, and one patient had no
      relief. Carbonic anhydrase activity has been demonstrated in the inner ear, and
      acetazolamide has been shown to affect the ion balance of the inner ear fluids.

PMID- 1992744
TI  - Reproducibility of topographic measurements of the normal and glaucomatous optic
      nerve head with the laser tomographic scanner.
AB  - We acquired five independent topographic images of the optic nerve head of eight
      normal eyes and eight eyes with primary open-angle glaucoma with a laser
      tomographic scanner. Each image had a field of view of 15 x 15 degrees with a
      resolution of 256 x 256 pixels. The pixel size was approximately 15 x 15 microns.
      The value of a pixel of a topographic image represented the height at this
      position. The mean height and the standard deviation over the five topographic
      images were calculated for each of the 65,536 pixel positions. The standard
      deviation of a single height measurement in normal eyes was 38.7 microns (range,
      23.4 to 62.2 microns) for areas in the peripapillary retina and 42.6 microns
      (range, 24.4 to 53.7 microns) for measurements within the optic nerve head area.
      In glaucomatous eyes, the standard deviation was 41.2 microns (range, 23.2 to
      59.6 microns) in the peripapillary retina and 49.4 microns (range, 28.1 to 72.8
      microns) within the optic nerve head. There was no significant difference between
      the standard deviation of a single height measurement in normal and glaucomatous
      eyes (P = .34 within the optic nerve head area; P = .57 on peripapillary retina).
      No correlation was found between standard deviation of the measurements and pupil
      size or age of the subject.

PMID- 1992745
TI  - Mucogenic secondary open-angle glaucoma in diffuse epithelial ingrowth treated by
      block-excision.
AB  - We treated a 40-year-old man with an acute, unilateral, open-angle glaucoma
      caused by a gelatinous translucent material in the anterior chamber. A clinical
      diagnosis of mucogenic secondary open-angle glaucoma caused by diffuse epithelial
      ingrowth after ocular trauma one year earlier was suspected, but a primary or
      secondary ciliary body or iris neoplasm could not be ruled out. A curative 9-mm
      block-excision was performed. Six years later, intraocular pressure was normal,
      and the visual function was unchanged. Light and electron microscopy disclosed an
      island of diffuse columnar epithelium with numerous goblet cells on the iris
      surface and copious mucinous material extending into the trabecular mesh-work.

PMID- 1992747
TI  - Microwave thermotherapy for choroidal hemangioma.

PMID- 1992746
TI  - Automated perimetry in glaucoma.

PMID- 1992748
TI  - Retinal vasculitis with proliferative retinopathy in a patient with evidence of
      Borrelia burgdorferi infection.

PMID- 1992749
TI  - Peripheral ulcerative keratitis related to Lyme disease.

PMID- 1992750
TI  - Malignant glaucoma after Nd:YAG cyclophotocoagulation.

PMID- 1992751
TI  - Candida albicans corneal ulcer associated with crack cocaine.

PMID- 1992752
TI  - Ketoprofen in the treatment of scleritis.

PMID- 1992753
TI  - Repair of a giant scleral ulcer with a scleral graft and tissue glue.

PMID- 1992754
TI  - Retained veirs rod and canaliculitis.

PMID- 1992755
TI  - Successful treatment of recurrent corneal erosion with Nd:YAG anterior stromal
      puncture.

PMID- 1992756
TI  - Rapidly progressive outer retinal necrosis in the acquired immunodeficiency
      syndrome.

PMID- 1992757
TI  - Successful medical management of Acanthamoeba keratitis.

PMID- 1992758
TI  - Detection of loss of heterozygosity in formalin-fixed paraffin-embedded tumor
      specimens by the polymerase chain reaction.
AB  - A polymerase chain reaction-based procedure was used for the detection of DNA
      length polymorphisms generated by naturally occurring genetic deletions or
      insertions of known sequence. This method consists of a simple one-step assay
      that does not require any restriction enzyme analysis or Southern blot
      hybridization, allowing identification in ethidium bromide-stained gels. The
      procedure described here was used to detect loss of heterozygosity at various
      loci, including the Hbb beta-globin gene cluster, in chemically induced mouse
      skin tumors, using a variety of tissue preparations, including microdissection of
      formalin-fixed, paraffin-embedded specimens, short-term cultures, and
      fluorescence-activated cell sorting of epithelial populations. This approach may
      be useful in detecting tumor-specific reduction to homozygosity at polymorphic
      chromosomal loci, allowing the mapping of putative tumor-suppressor loci involved
      in carcinogenesis.

PMID- 1992759
TI  - Longitudinal histopathologic assessment of rejection after bladder-drained canine
      pancreas allograft transplantation.
AB  - In preparation for assessment of percutaneous biopsies in our clinical pancreas
      transplant program, a working knowledge of the histopathologic changes after
      transplantation was obtained in a longitudinal open biopsy study of 16 dogs
      receiving bladder-drained whole pancreas allografts. Edema, extravasation of
      polymorphs, and lymphocytes associated with focal parenchymal injury were early,
      invariable, and probably nonspecific findings. The initial feature of unmodified
      rejection was the appearance of capillary and small vein endothelial changes with
      mainly perivascular inflammatory cell infiltration. Acinar cell loss occurred
      early and was progressive, whereas islets and ducts were relatively preserved,
      indicating that acinar tissue may be more vulnerable to lytic necrosis when
      damaged. Functional rejection, determined by fasting urinary amylase levels, was
      at a stage of extensive and irreversible necrosis. Functioning grafts in
      immunosuppressed dogs had minor and transient endothelial changes with absence of
      class II antigen staining of parenchymal cells.

PMID- 1992760
TI  - Characterization of preneoplastic and neoplastic lesions in the rat pancreas.
AB  - Nodules of acinar cells with increased proliferative potential develop in the
      pancreas of carcinogen-treated rats and in untreated aged rats. Large nodules are
      classed as adenomas. Phenotypic and genotypic characteristics of nodule cells
      were compared with normal pancreas and transplantable acinar cell carcinomas by
      several methods. Nuclei of acinar cells from normal pancreas, adenomas, and three
      carcinomas in situ had normal diploid DNA content as determined by flow
      cytometry. One of two primary carcinomas had a hypodiploid DNA content. Two of
      three transplantable carcinomas were aneuploid with a DNA content in the
      tetraploid range. Explants from nodules and adenomas failed to grow in soft agar,
      whereas several carcinomas were positive in this assay. A primary carcinoma was
      serially transplanted, but transplantation of nodules or adenomas failed.
      Transfection of DNA from carcinomas in situ yielded a higher frequency of NIH 3T3
      transformants than DNA from adenomas. DNAs from the transformants did not contain
      ras sequences. These studies indicate that cells from nodules and adenomas have
      low growth potential and lack critical phenotypic and genotypic characteristics
      of transformed malignant cells that were present in some primary and transplanted
      carcinomas.

PMID- 1992761
TI  - Ultrastructure of respiratory cilia of WIC-Hyd male rats. An animal model for
      human immotile cilia syndrome.
AB  - The WIC-Hyd rat is a mutant from the Csk: Wistar-Imamichi rat, with spontaneous
      hydrocephalus. In male rats, the hydrocephalus is severe and about one half of
      hydrocephalic male littermates possess situs inversus totalis. Ependymal cilia in
      these animals are immotile, and this defect is regarded as a mechanical cause of
      hydrocephalus. This paper presents the ultrastructural features of respiratory
      cilia in these rats in comparison with those in human immotile cilia syndrome.
      The respiratory cilia in these rats also are immotile and the dynein arms are
      missing, as in human cases. Previously only eight dogs with immotile cilia
      syndrome and a mutant hydrocephalic-polydactyl mouse were reported with respect
      to these phenomena. However the WIC-Hyd rat is the first useful animal model for
      human immotile cilia syndrome, and further studies may serve to clarify the
      genetic background of this condition.

PMID- 1992762
TI  - Induction of different morphologic features of malignant melanoma and pigmented
      lesions after transformation of murine melanocytes with bFGF-cDNA and H-ras, myc,
      neu, and E1a oncogenes.
AB  - Malignant melanomas show a remarkable degree of heterogeneity because of
      different morphologic features, biologic behavior, and prognosis. In this
      communication, the authors attempted to correlate morphologic heterogeneity of
      melanomas with transformation by different activated oncogenes; they studied the
      histologic features of melanocytic lesions induced by murine melanocytes
      transformed by basic fibroblast growth factor (b-FGF-cDNA) or H-ras, neu, myc,
      and E1a oncogenes, and the lesions were compared with those observed in human
      pathology. Tumors formed after grafting onto syngenic mice or subcutaneous
      injections in nude mice were studied. In syngenic mice, benign melanocytic
      lesions reminiscent of intradermal nevus were observed with melanocytes
      transformed with b-FGF-cDNA, and myc and E1a oncogenes. Benign lesions were also
      formed by neu-transformed melanocytes when they were grafted concomitantly with
      keratinocytes, whereas malignant tumors were formed by the same cells when
      grafted alone or together with fibroblasts. In contrast, H-ras melanocytes always
      formed malignant tumors. In nude mice, b-FGF-transformed melanocytes induced
      benign lesions, whereas transformed melanocytes by the other oncogenes formed
      malignant tumors with distinctive and homogeneous morphologic features that
      depended on the transforming oncogene. Melanomas with either epithelioid cell,
      spindle cell, small round cell, and anaplastic cell growth patterns could be
      distinguished after transformation with H-ras, neu, E1a, and myc oncogenes,
      respectively. These various histologic types are analogous to those that may be
      observed in human melanomas, even within the same tumor. These studies suggest a
      possible molecular mechanism for tumor heterogeneity in which distinct oncogenes
      or oncogenelike activities can be activated in different tumors or discrete parts
      of the same tumor.

PMID- 1992763
TI  - Immunohistochemical localization and quantification of the 3-(cystein-S-yl)
      acetaminophen protein adduct in acetaminophen hepatotoxicity.
AB  - Acetaminophen overdose causes severe hepatotoxicity in humans and laboratory
      animals, presumably by metabolism to N-acetyl-p-benzoquinone imine: and binding
      to cysteine groups as 3-(cystein-S-yl)acetaminophen-protein adduct. Antiserum
      specific for the adduct was used immunohistochemically to demonstrate the
      formation, distribution, and concentration of this specific adduct in livers of
      treated mice and was correlated with cell injury as a function of dose and time.
      Within the liver lobule, immunohistochemically demonstrable adduct occurred in a
      temporally progressive, central-to-peripheral pattern. There was concordance
      between immunohistochemical staining and quantification of the adduct in hepatic
      10,000g supernate, using a quantitative particle concentration fluorescence
      immunoassay. Findings include: 1) immunochemically detectable adduct before the
      appearance of centrilobular necrosis, 2) distinctive lobular zones of adduct
      localization with subsequent depletion during the progression of toxicity, 3)
      drug-protein binding in hepatocytes at subhepatotoxic doses and before depletion
      of total hepatic glutathione, 4) immunohistochemical evidence of drug binding in
      the nucleus, and 5) adduct in metabolically active and dividing hepatocytes and
      in macrophagelike cells in the regenerating liver.

PMID- 1992764
TI  - In vivo biologic and immunohistochemical analysis of interleukin-1 alpha, beta
      and tumor necrosis factor during experimental endotoxemia. Kinetics, Kupffer cell
      expression, and glucocorticoid effects.
AB  - Using a model of sepsis induced by parenteral challenge of mice with bacterial
      lipopolysaccharide (LPS), the authors analyzed the in vivo expression of
      interleukin-1 (IL-1) alpha,beta and tumor necrosis factor (TNF). Both TNF and IL
      1 alpha,beta were detected in hepatic sinusoidal macrophages (Kupffer cells),
      immunohistochemically. Kinetic analysis showed a clear sequence of synthesis.
      Tumor necrosis factor was produced first, reaching maximal expression at 1 hour
      after LPS challenge, then rapidly disappeared. IL-1 beta followed, reaching
      maximal expression at 2 to 3 hours, then dropped off by 6 hours. Interleukin-1
      alpha expression reached a peak at 6 hours and had disappeared by 18 hours.
      Analysis of serum bioactivity also revealed sequential expression that correlated
      with immunohistochemical findings. Tumor necrosis factor was maximal at 1 hour
      and IL-1 at 6 hours. The IL-1 bioactivity was not due to interleukin-6 (IL-6), as
      this was depleted from specimens by immunoabsorption. Also IL-6 bioactivity
      reached maximal levels at 3 hours, earlier than IL-1. Pretreatment with 4 mg/kg
      dexamethasone significantly decreased Kupffer cell expression of TNF and IL-1
      alpha (about 80% and 60% suppression, respectively) but had less effect on IL-1
      beta expression (about 30% suppression). Accordingly, serum levels of TNF were
      suppressed by 75% while serum IL-1 was decreased by 39%, indicating differential
      sensitivity of these cytokines to glucocorticoids. Endogenous corticosteroid
      levels increased as TNF levels decreased, supporting the contention that
      glucocorticoids regulate TNF synthesis. In contrast, IL-1 levels rose
      concurrently with corticosterone. These data indicate a sequential activation of
      cytokine gene expression in vivo, which may be critical to the cascade of events
      leading to septic shock, and provide evidence that Kupffer cells are a major
      source of cytokines in endotoxemia. Finally, the differential sensitivity of
      cytokine expression to glucocorticoids may in part explain the inadequacy of the
      latter in the treatment of sepsis.

PMID- 1992765
TI  - Systemic amyloidosis in transgenic mice carrying the human mutant transthyretin
      (Met30) gene. Pathologic similarity to human familial amyloidotic polyneuropathy,
      type I.
AB  - To analyze the pathologic processes of amyloid deposition in type I familial
      amyloidotic polyneuropathy (FAP), mice were made transgenic by introducing the
      human mutant transthyretin (TTR) gene. In these transgenic mice, amyloid
      deposition started in the gastrointestinal tract, cardiovascular system, and
      kidneys 6 months after birth and extended to various other organs and tissues
      with advancing age. At age 24 months, the pattern of amyloid deposition was
      similar to that observed in human autopsy cases of FAP, except for its absence in
      the choroid plexus and in the peripheral and autonomic nervous systems. Amyloid
      deposition was shown to be composed of human mutant TTR and, in addition, mouse
      serum amyloid P component. These results clearly indicate that human variant TTR
      produced in transgenic mice deposits is a major component of amyloid fibrils in
      various organs and tissues. Thus this animal model is useful for analyzing how
      amyloid deposition initiates and proceeds in FAP.

PMID- 1992766
TI  - Differential expression of basement membrane collagen chains in diabetic
      nephropathy.
AB  - Diabetic nephropathy is characterized by progressive expansion of mesangial
      matrix and thickening of the glomerular basement membrane (GBM). Kidney tissues
      from 13 patients with insulin-dependent diabetes mellitus were studied by
      immunohistochemical techniques for the distribution of three recently described
      collagen peptides (M28+, M28 [Good-pasture antigen], and Alport antigen) and
      various components of classical type IV collagen [alpha 1(IV) noncollagenous (NC)
      globular domain, alpha 2(IV) NC, 7S, triple helix]. Recently M28 and M28+ were
      designated as NC monomers of alpha 3(IV) and alpha 4(IV) based on limited amino
      acid sequencing. During the course of the disease, the distribution of the M28
      chains and the Alport peptide segregated completely from that of classical type
      IV collagen. In diabetic kidneys, antibodies to the M28 and Alport peptides
      reacted intensely with the thickened GBM but not with the mesangium. In contrast,
      the reactivity of antibodies to various components of classical type IV collagen
      was prominent within the expanded mesangial matrix with significant decrease in
      reactivity in the peripheral capillary wall. In hyalinized glomeruli, components
      of classical type IV collagen virtually disappeared, whereas the M28 and Alport
      peptides persisted in the collapsed GBM. These studies support the view that
      expansion of the mesangial matrix and thickening of the GBM involve separate and
      distinct collagen components. The differential expression of the M28 and Alport
      peptides compared with that of classical type IV collagen may be a consequence of
      differing sites of synthesis (classical type IV collagen from
      endothelial/mesangial cells and M28 and Alport chains from visceral epithelial
      cells), independent control mechanisms, and/or differences in degradation.

PMID- 1992767
TI  - Human immunodeficiency virus-infected multinucleated histiocytes in oropharyngeal
      lymphoid tissues from two asymptomatic patients.
AB  - Human immunodeficiency virus (HIV)-infected multinucleated giant cells previously
      were detected only in the central nervous system of HIV-positive patients.
      Reported here are the first cases in which such infected cells were observed
      outside the central nervous system, in the oropharyngeal lymphoid tissues.
      Tonsils and adenoids were removed individually from two asymptomatic homosexual
      men. Follicular hyperplasia and many interfollicular multinucleated giant cells
      most often in contact with or in close proximity of the mucous membrane were
      seen. The latter were positive for lysozyme, alpha-1 anti-chymotrypsin, OKM1, and
      S-100 protein in accordance with a histiocytic origin. In situ hybridization with
      an HIV envelope-specific RNA probe demonstrated the presence of viral RNA in
      these multinucleated giant cells. These findings support the role of peripheral
      histiocytes as a primary virus reservoir early in the disease. They also
      underline the potential role of oropharyngeal tissue as a primary target in some
      cases.

PMID- 1992768
TI  - Methodologic considerations important in the accurate quantitation of aortic
      smooth muscle cell replication in the normal rat.
AB  - While a number of studies have compared replication rates for vascular smooth
      muscle cells under different conditions, the absolute frequency of smooth muscle
      cell replication within the vessel wall has not been defined. This study reports
      a comparison of four parameters that might be expected to alter the accuracy of
      such counts. Neither autoradiograph exposure time, within specific time limits,
      nor dose of tritiated thymidine are major variables. Differences in absolute
      values obtained by autoradiography of enzyme-dispersed cells versus cells in
      cross-section, however, are reproducible. A comparison of frequency data from
      animals injected with tritiated thymidine during a 24-hour period compared with
      data from animals infused continuously for 1 week suggests that continuous
      infusion allows accumulation of labeled cells over time at a rate that is
      predictable from data of animals injected during 24 hours. In the current study
      it was found that although the frequency of tritiated thymidine-labeled thoracic
      aorta smooth muscle cells may vary according to the technique used in preparing
      the tissue, the daily rate of replication in a 4-month-old rat is estimated to be
      approximately 0.047% per day.

PMID- 1992769
TI  - Tumor necrosis factor induces apoptosis (programmed cell death) in normal
      endothelial cells in vitro.
AB  - Tumor necrosis factor (TNF) is cytotoxic for many tumoral cell lines, whereas
      normal cells generally are considered resistant to this action. This study shows
      that this cytokine causes massive death of bovine endothelial cells in primary
      culture in a concentration- and time-dependent manner. Dying cells exhibit all
      the ultrastructural changes and the inter-nucleosome cleavage of DNA associated
      with apoptosis or 'programmed cell death.' This is the first report clearly
      showing a direct toxicity of TNF on endothelial cells and demonstrating that this
      results from the induction of the program of apoptotic death. Our observation
      raises the possibility that hemorrhagic necrosis in vivo, after treatment with
      TNF, might involve a direct cytocidal action on endothelial cells of the tumor
      neovasculature.

PMID- 1992770
TI  - Marker profile of different phases in the transition of normal human ovarian
      epithelium to ovarian carcinomas.
AB  - To investigate whether early changes in the transformation of normal ovarian
      epithelial cells into tumor cells can be detected with monoclonal antibodies, a
      comparative immunohistochemical study was performed on normal human ovarian
      mesothelial cells, cystomas, cystadenomas, ovarian carcinomas, as well as
      granulosa cell tumor. Using monoclonal antibodies against different keratin
      subtypes, it was shown that mesothelial cells, ovarian cysts, cystadenomas, and
      carcinomas all reacted positively with broad-spectrum anti-keratin monoclonal
      antibodies (MAbs), as well as with MAbs to keratins 7, 8, 18, and 19. Keratins 4
      and 13 were not found in mesothelial cells, but positive groups of cells were
      identified in several cystomas, adenomas, and carcinomas. While mesothelial cells
      did not react with the pan-epithelial marker BW495/36, invaginating metaplastic
      mesothelial cells, inclusion cysts, cystomas, adenomas, and carcinomas showed an
      increasing reactivity with BW495/36, with an increasing degree of malignancy. The
      reactivity of MAbs against ovarian carcinoma-associated antigens (OV-TL 3, OC
      125, MOv 18, and OV-TL 10) was limited to weak staining reaction in some
      mesothelial cells but were found to be positive on more than 50% of the ovarian
      cystadenomas and more than 90% of the ovarian carcinomas. Thecal and granulosa
      cells of primordial, primary, and secondary follicles all reacted positively with
      antibodies to the broad-spectrum keratins OV-TL 12/5 and RCK 102, and to keratins
      8 and 18, but not with keratins 4, 7, 13, and 19. These keratins decreased or
      disappeared in granulosa cells of mature follicles (Graafian follicles), whereas
      granulosa cell tumors did not react with anti-keratin antibodies. The reactivity
      of BW 495/36 was negative or limited to traces in some granulosa cells. Ovarian
      carcinoma-associated antigens were not expressed in granulosa cells or granulosa
      cell tumors. The data indicate that mesothelial cells undergoing metaplastic
      changes finally resulting in ovarian cystadenomas (and carcinomas) initiate the
      synthesis of a 200-kd glycoprotein recognized by MAb (BW 495/36), the production
      of ovarian carcinoma associated antigens, in addition to focal production of
      keratin 4 and/or 13, as seen in several samples. The granulosa cell tumors
      decrease or switch off their keratin production and remain negative for the 200
      kd glycoprotein and the ovarian carcinoma-associated antigens.

PMID- 1992771
TI  - Glomerular basement membrane expansion in passive Heymann nephritis. Absence of
      increased synthesis of type IV collagen, laminin, or fibronectin.
AB  - The distribution and synthetic rate of glomerular basement membrane components
      was examined in the Passive Heymann Nephritis model of experimental membranous
      nephropathy. The extensive tissue injury that developed included subepithelial
      electron-dense deposits, podocyte foot process effacement, and expansion of the
      glomerular basement membrane. Levels of mRNA for type IV collagen, laminin, and
      fibronectin from isolated glomeruli was quantitated by slot-blot analysis and
      showed no change in experimental animals as compared to controls at either 1
      week, 3 weeks, or 3 months after disease induction. Immunoelectron microscopy
      with gold-labeled anti-laminin IgG revealed no difference in the number of
      particles bound to the glomerular basement membrane of experimental animals and
      controls. Immunofluorescence with both type IV collagen antisera and anti-laminin
      antibody showed no difference in the intensity or pattern of staining. Despite
      extensive glomerular damage and glomerular basement membrane thickening, no
      evidence was found for either an increase in the synthetic rate of type IV
      collagen, laminin, or fibronectin or for an accumulation of basement membrane
      laminin within the damaged glomeruli. Alternate processes, such as diminished
      density of matrix components or accumulation of other unmeasured matrix
      constituents, presumably account for the expansion of the glomerular basement
      membrane seen in experimental membranous nephropathy.

PMID- 1992772
TI  - Selective differences in macrophage populations and monokine production in
      resolving pulmonary granuloma and fibrosis.
AB  - Alveolar macrophages (AM) and their production of interleukin-1-like activity (IL
      1) and macrophage-derived growth factor for fibroblasts (MDGF) were examined
      during chronic inflammatory reactions leading to either granuloma formation or
      fibrosis. Groups of five rats each received, respectively, a single transtracheal
      injection of xonotlite, attapulgite, short chrysotile 4T30, UICC chrysotile B
      asbestos, or saline. One month later, such treatments induced either no change
      (xonotlite), granuloma formation (attapulgite and short chrysotile 4T30), or
      fibrosis (UICC chrysotile B). By 8 months, however, the granulomatous reactions
      had resolved or greatly diminished, whereas the fibrosis persisted irreversibly.
      Parallel examination of cell populations obtained by bronchoalveolar lavage
      revealed that multinucleated giant macrophages (MGC) were present in lavage
      fluids of animals with resolving granulomatous reactions but absent in those
      obtained from animals with lung fibrosis. Evaluation of monokine production by
      inflammatory macrophages also revealed significant differences. Enhanced
      production of IL-1-like activity was seen in both types of lung injury, although
      especially during the early stage (1 month) and decreased thereafter (8 months).
      By contrast, augmentation of MDGF production was observed in animals with lung
      fibrosis only and persisted up to 9 months. Taken together, these data indicate
      that production of selected cytokines, as well as AM differentiation along a
      given pathway, may modulate the outcome of a chronic inflammatory response.

PMID- 1992773
TI  - Regulation of water and salt transport in collecting duct through calcium
      dependent signaling mechanisms.

PMID- 1992774
TI  - Basolateral transport pathways for K+ and Cl- in rabbit proximal tubule: effects
      on cell volume.
AB  - To characterize the nature of K+ and Cl- transport pathways across basolateral
      membrane of rabbit proximal convoluted tubule, we used quantitative video
      microscopy to measure cell volume changes induced by rapid basolateral K+ and Cl-
      concentration changes. Elevating basolateral K+ resulted in cell swelling, which
      was largely inhibited by replacement of basolateral Cl- with cyclamate (85%) or
      by addition of 2 mM Ba2+ (72%). Substitution of basolateral Cl- by NO3- enhanced
      cell swelling, whereas substitution of Cl- by I- did not affect the K(+)-induced
      volume changes. Removal of Cl- from the bath reversed the cell swelling induced
      by raising K+ in the bath. Steady-state cell volume was 28% greater in hypotonic
      medium (250 mosmol/kgH2O) than in hypertonic medium (350 mosmol/kgH2O), and the
      rate of increase in cell volume induced by raising K+ was three times higher in
      hypotonic than in hypertonic medium. Substitution of Cl- by NO3- did not alter
      the effect of medium osmolality on K(+)-induced cell swelling, whereas addition
      of 0.2 mM diphenylamine-2-carboxylate inhibited the response (63%). We conclude
      that K(+)-induced cell swelling results from entry of K+ and Cl- into the cell
      across the basolateral membrane; it is proposed that transport of KCl across the
      basolateral cell membrane proceeds largely through two separate conductive
      pathways for K+ and Cl-. Cell swelling activates KCl transport occurring via K+
      and Cl- channels across the basolateral membrane.

PMID- 1992775
TI  - Myo-inositol and D-glucose transport in rat glomerular and cultured mesangial
      cells.
AB  - Myo-inositol (MI) is the precursor of membrane-bound phosphoinositides important
      for transmembrane signaling. This study examines whether freshly isolated whole
      glomeruli can be used to characterize intact cell transport kinetics for MI and D
      glucose. Transport properties of cultured mesangial cells are compared. Glomeruli
      greater than 95% tubule free were isolated from Sprague-Dawley rat kidney cortex
      by means of selective sieving. Scanning electron microscopy revealed substantial
      damage of glomerular epithelial cells, whereas endothelial and mesangial cells
      remained intact. Specific [3H]MI uptake (7-180 min, 37 degrees C) was observed in
      presence of 5.5 mM D-glucose when L-[14C]glucose was used as a marker of
      nonspecific uptake. With ouabain (3 mM), or when Na was replaced with N-methyl-D
      glucamine, choline, or Li, specific MI uptake was reduced by 95%. A single high
      affinity, Na-dependent MI transport site on glomerular cells with Km of 16.5 +/-
      1.4 (SE) microM and Vmax of 947 +/- 56 (SE) fmol.mg protein-1.min-1 was observed
      for 0.75-100 microM MI. D-glucose competitively inhibited MI transport. Specific
      D-[3H]-glucose transport was Na independent. Phlorizin inhibition of D-glucose
      and MI uptake was in keeping with Na-independent D-glucose transport. Km and Vmax
      for MI uptake in cultured mesangial cells were 42.7 +/- 7.1 microM and 1,474 +/-
      192 fmol.mg protein-1.min-1, respectively. We conclude that freshly isolated
      glomeruli can be used to study cellular transport function that may be modified
      in disease states.

PMID- 1992776
TI  - Role of prostaglandins and endothelium-derived relaxing factor on the renal
      response to acetylcholine.
AB  - Acetylcholine (ACh) stimulates the endothelial release of prostacyclin and
      endothelium-derived relaxing factor (EDRF). However, the relative participation
      of these substances in mediating the renal effects of ACh remains undefined. To
      elucidate this issue, we studied the modifications of renal responses to intra
      renal ACh infusion (25 ng.kg-1.min-1) produced by blocking the synthesis of EDRF
      and/or prostaglandins (PG) in anesthetized dogs. ACh induced a significant
      increase in renal blood flow (RBF) (34%), urine volume (UV) (450%), and urinary
      sodium excretion (UNaV)(259%), which remained unaltered after blocking the
      synthesis of EDRF [NG-monomethyl-L-arginine (LNMMA), 50 micrograms.kg-1.min-1
      intrarenal] or PG (meclofenamate, 5 mg/kg iv). However, the simultaneous
      administration of meclofenamate and LNMMA prevented the ACh-induced increase in
      RBF and UV but not in UNaV. The concomitant infusion of L-arginine but not D
      arginine prevented these blocking effects of LNMMA. It was concluded that the ACh
      induced increases in RBF and UV, but not UNaV, are mediated by both PG and EDRF.
      The hemodynamic and diuretic effect of either one of these mediators can be fully
      compensated during the blockade of the other.

PMID- 1992777
TI  - Angiotensin II stimulates ammoniagenesis in canine renal proximal tubule
      segments.
AB  - To determine whether angiotensin II (ANG II) affects ammoniagenesis in renal
      proximal tubule, ammonia production was measured in suspensions of canine renal
      proximal tubule segments (PCT) incubated with L-glutamine and varying
      concentrations of ANG II. Ammonia production from PCT was significantly increased
      by 15.5 +/- 1.1% in the presence of ANG II (10(-6) M) at 2 h. Similarly, glucose
      production significantly increased by 10.0 +/- 0.9%. Half-maximal stimulation
      occurred at approximately 10(-9) M ANG II. Stimulation of ammonia production by
      ANG II was blocked in the presence of the ANG II antagonist, [Sar1-Ile8]ANG II
      (10(-6) M). Enhancement of ammonia production in PCT by ANG II occurred in
      acidotic and neutral media but not in alkalotic medium. When extracellular [Na+]
      = intracellular [Na+] ANG II significantly increased ammonia production in PCT.
      Absence of extracellular Ca2+ or addition of trifluoperazine or N-(6-aminohexyl)
      5-chloro-1-naphthalene sulfonamide (W-7) (Ca2(+)-calmodulin-dependent pathway
      inhibitors) blocked the action of ANG II to enhance ammonia production. We
      conclude that ANG II stimulates ammonia and glucose production in canine renal
      PCT via a receptor-mediated signal. The action of ANG II on ammoniagenesis may be
      mediated by a calcium-calmodulin-dependent pathway. Stimulation of ammoniagenesis
      in vitro under normal and acidotic conditions may reflect a role in vivo for ANG
      II in the regulation of renal acid-base metabolism.

PMID- 1992779
TI  - Role of endogenous endothelin on renal functions in rats.
AB  - This study was conducted to determine the involvement of endogenous endothelin
      (ET), a novel potent vasoconstricting peptide, in systemic and renal hemodynamics
      and in the renin-angiotensin system by inhibiting ET action via infusion of a
      specific ET antiserum at a time of altered sodium balance. Infusion of 1:50
      diluted ET antiserum, which completely inhibited renal vasoconstriction by the
      exogenously administered ET (0.25 to 1.0 nmol/kg), caused an increase in urinary
      sodium excretion and fractional excretion of sodium and a decrease in plasma
      renin concentration without significant changes in blood pressure, heart rate,
      glomerular filtration rate, renal plasma flow, and urine volume compared with the
      values with nonimmune serum in conscious rats fed a low-salt diet. A time control
      study showed no significant changes in all parameters. These results suggest that
      the state of low- compared to high-salt intake causes a relatively stronger
      activity of endogenous ET, and that the endogenous ET contributes to the
      adaptative modulations of sodium excretion via renal tubular action and renin
      release in association with the changed state of sodium balance.

PMID- 1992778
TI  - Hyposmotic activation of Ca-activated K channels in cultured rabbit kidney
      proximal tubule cells.
AB  - The effects of hypotonicity on K currents were examined in the single cells
      isolated from cultured rabbit kidney proximal tubule cells. Using the whole cell
      clamp technique [pipette-filling solution was 145 mM KCl with 0 Ca plus 0.08 mM
      ethylene glycol-bis(beta-aminoethylether)-N,N,N',N'-tetraacetic acid], we found
      that the K currents increased from 0.8 to 43.5 +/- 12.5 pA at a holding potential
      (Vp) = 0 mV in response to reduction of extracellular osmolality from 290 to 218
      mosmol/kgH2O (n = 8). Removal of Ca from bath reduced osmotic activation of K
      currents by 74% (n = 10). Application of 5 mM Ba to the bath completely inhibited
      the K currents at Vp = 0 mV but not at Vp = 60 mV. Dominant K currents were shown
      to be Ca-activated (maxi) K channels by their single-channel conductance (175 +/-
      8.6 pS) and Ca dependence. Relative permeability ratio (PK/PNa) was 9. In
      conclusion, hypotonic-induced cell swelling stimulates Ca-activated K channels,
      which may play a role in cell volume regulation.

PMID- 1992780
TI  - Tubuloglomerular feedback dynamics and renal blood flow autoregulation in rats.
AB  - To decide whether tubuloglomerular feedback (TGF) can account for renal
      autoregulation, we tested predictions of a TGF simulation. Broad-band and single
      frequency perturbations were applied to arterial pressure; arterial blood
      pressure, renal blood flow and proximal tubule pressure were measured. Data were
      analyzed by linear systems analysis. Broad-band forcings of arterial pressure
      were also applied to the model to compare experimental results with simulations.
      With arterial pressure as the input and tubular pressure, renal blood flow, or
      renal vascular resistance as outputs, the model correctly predicted gain and
      phase only in the low-frequency range. Experimental results revealed a second
      component of vascular control active at 100-150 mHz that was not predicted by the
      simulation. Forcings at single frequencies showed that the system behaves
      linearly except in the band of 33-50 mHz in which, in addition, there are
      autonomous oscillations in TGF. Higher amplitude forcings in this band were
      attenuated by autoregulatory mechanisms, but low-amplitude forcings entrained the
      autonomous oscillations and provoked amplified oscillations in blood flow,
      showing an effect of TGF on whole kidney blood flow. We conclude that two
      components can be detected in the dynamic regulation of renal blood flow, i.e., a
      slow component that represents TGF and a faster component that most likely
      represents an intrinsic vascular myogenic mechanism.

PMID- 1992781
TI  - Transfer of Na transport inhibition in proximal tubules from saline volume
      expanded to nonexpanded rats.
AB  - In dual micropuncture experiments the shrinking drop technique was used to
      measure volume flux with artificial tubular fluid (AF) alternating with harvested
      tubular fluid (HTF) during saline volume-expanded (VE) and nonexpanded (NE)
      periods. In VE rats, volume flux (Jv) (nl.mm-1.min-1) with AF was 1.78 +/- 0.08
      (means +/- SE) during NE and was reduced to 1.39 +/- 0.09 (P = 0.01) during
      subsequent VE, whereas with randomly alternating HTF during VE it was 1.07 +/-
      0.08 (P less than 0.0001 and less than 0.03, respectively). Jv with HTF from NE
      rats tested in the VE rats was 1.20 +/- 0.06, which is significantly higher than
      that measured with their own HTF (Wilcoxon rank, P = 0.05). In NE rats Jv was
      1.65 +/- 0.10 and 1.69 +/- 0.10 with AF and HTF and was 1.28 +/- 0.07 (P less
      than 0.001 from both) with HTF obtained from VE rats. Elemental analysis of
      reaspirated tubular fluids showed no significant differences in Na or Cl
      concentrations among any of the fluids. It is concluded that during VE, a
      transferable Na transport inhibitor appears in proximal tubular fluid, which,
      together with a changed proximal tubular epithelium, possibly due to physical
      forces, accounts for proximal tubular Na transport inhibition during VE.

PMID- 1992782
TI  - Single-nephron filtration rate and proximal reabsorption in aging rats.
AB  - Age-related changes in the function of individual nephrons were investigated by
      micropuncture experiments measuring single-nephron filtration rates (SNGFR) and
      proximal reabsorptions in 10-, 20-, and 30-mo-old rats. The animals were female
      WAG/Rij rats with low incidence of chronic progressive nephropathy, no loss of
      nephrons, and renal hypertrophy of both kidneys in the oldest animals. Mean SNGFR
      values per gram kidney weight were 41.4 +/- 1.1, 37.1 +/- 1.5, and 32.2 +/- 1.1
      nl.min-1.g kidney wt-1 (n = 41) in the 10-, 20-, and 30-mo-old animals,
      respectively. This age-related decrease in filtration was no longer apparent when
      SNGFR values were expressed per nephron (means 24.3 +/- 0.7, 23.7 +/- 0.9, and
      24.4 +/- 0.9 nl/min. Individual filtered loads of sodium, potassium, calcium, and
      magnesium and their absolute reabsorption by the proximal tubule were not
      different in the three age groups; however, absolute and fractional reabsorptions
      of phosphate decreased significantly in the 30-mo-old rats. These results
      indicate that, with the exception of phosphate, individual filtrations and
      proximal reabsorptions are well maintained in aging rats free of disease. This
      may be related to the observed renal hypertrophy.

PMID- 1992783
TI  - Role of renal nerves on pressure natriuresis in spontaneously hypertensive rats.
AB  - An abnormal rightward shift of the pressure-natriuresis curve is a well known
      feature of the renal function in hypertension. The participation of intrinsic
      neural factors in the kidney in this phenomenon was investigated in anesthetized
      young and adult spontaneously hypertensive rats (SHR). At 7-8 wk of age, the
      renal pressure-diuresis curve and pressure-natriuresis curve were shifted to the
      left in denervated SHR compared with innervated animals. Fractional excretion of
      sodium was higher, and plasma renin activity was lower in denervated SHR.
      Glomerular filtration rate was not affected by renal denervation. In 13- to 15-wk
      old SHR, renal denervation did not affect the pressure-diuresis and -natriuresis
      curves, although other parameters were changed compared with the results at 7-8
      wk. In Wistar-Kyoto rats, the pressure-diuresis curve was shifted to the left by
      renal denervation at both ages. These results suggest that the renal nerves have
      an important effect on the renal pressure-diuresis and -natriuresis curves.
      However, renal innervation cannot be thought to cause an abnormal rightward shift
      of the pressure-diuresis and -natriuresis curves in SHR, especially in the
      established stage of hypertension.

PMID- 1992784
TI  - Vasopressin is involved in renal effects of high-protein diet: study in
      homozygous Brattleboro rats.
AB  - The present study was designed to test the possible role of vasopressin in the
      renal response to dietary protein. This possibility was suggested by the
      similarity of effects on renal function and morphology of chronic high-protein
      intake and chronic stimulation of urine concentration. Adult male Brattleboro
      rats, genetically unable to produce vasopressin, were fed high-protein (32%
      casein = HP, n = 8) or low-protein (10% casein = LP, n = 9) diet for 7 wk. Renal
      function was evaluated by clearance techniques based on 24-h urine collections in
      metabolic cages. The response to a single injection of the vasopressin analogue 1
      desamino-8-D-arginine vasopressin (DDAVP) was also tested. Kidney weight and
      height of the different renal zones were assessed at the end of the study. HP
      diet increased urea excretion nearly sevenfold. Water intake increased by 57% (P
      less than 0.001) and urine flow rate by 71% (P less than 0.01). Urine osmolality
      rose from 104 to 181 mosmol/kgH2O (P less than 0.001). At variance with what
      occurs in rats with endogenous vasopressin (Sprague-Dawley; Bouby, N., et al.
      Kidney Int 34: 4-12, 1988), HP diet increased creatinine clearance per unit body
      weight by only 14% and did not change free water clearance, renal mass, and
      height of inner stripe of outer medulla. However, the rise in urine osmolality
      and drop in free water clearance after DDAVP were significantly greater in HP-
      than in LP-fed Brattleboro rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1992785
TI  - Perfused prenodal lymphatics are constricted by prostaglandins.
AB  - Prostaglandins may contribute to the control of lymph flow by affecting lymphatic
      vessel contractility. We measured the pressure in perfused prenodal lymphatic
      vessel in the paw of the anesthetized dog as affected by administration of
      prostaglandins E1, E2, F2 alpha or arachidonic acid. The forelimb was perfused at
      constant flow with blood obtained from a femoral artery. Systemic arterial,
      central venous, and forelimb vascular pressures were measured. When added to the
      lymphatic perfusate, all of the prostaglandins and arachidonic acid caused
      constriction of lymphatic vessels. Perfusion of prenodal lymphatics separated
      from downstream nodes and vessels showed that this constriction occurred
      primarily in prenodal vessels. However, only prostaglandin F2 alpha caused
      lymphatic constriction when infused into the blood to the forelimb. Because
      prostaglandins are a common component of the lymph leaving an area of tissue
      damage, these results are compatible with the possibility that prostaglandins, by
      directly affecting lymphatics, help modulate lymph flow following local injury.

PMID- 1992786
TI  - Myocardial blood flow, metabolism, and function with repeated brief coronary
      occlusions in conscious ponies.
AB  - Studies were performed in the conscious pony instrumented with a Doppler flow
      probe and hydraulic occluder on the left anterior descending coronary artery
      (LAD), sonomicrometry crystals and intraventricular micromanometer in the left
      ventricle, and catheters in the left atrium and anterior interventricular vein.
      Two-minute LAD occlusions were performed every 30 min continuously or during
      working hours. Data on release of catabolites (potassium, hydrogen ions, and
      lactate) and norepinephrine from the initially dysfunctional region were obtained
      periodically during a regimen of 445 +/- 56 occlusions in six animals. Regional
      myocardial blood flow was measured (microsphere method) before and after an
      occlusion regimen in four animals. Marked release of catabolites and
      norepinephrine from the initially dysfunctional region was noted in association
      with early occlusions when myocardial segment function was severely reduced. With
      further occlusions, release of these substances decreased while segment function
      improved. Blood flow was markedly decreased in the initially dysfunctional region
      during an early occlusion but was at the control level during a later occlusion.
      Although the metabolic findings are consistent with protection due to "ischemic
      preconditioning" and no increase in collateral perfusion, the inverse
      relationship noted between catabolite release and segment function is best
      explained by flow-dependent mechanisms. These results, together with the
      myocardial blood flow data, serve to validate a previous assumption that
      protection against regional myocardial dysfunction under these conditions is due
      to increased collateral perfusion.

PMID- 1992787
TI  - Phosphorylated compounds and function in isolated hearts: a 31P-NMR study.
AB  - The potential role of phosphorylated compounds in the control of myocardial cell
      respiration was investigated by means of 31P-nuclear magnetic resonance (NMR)
      spectroscopy. Isolated isovolumic rat hearts, perfused with a 9 mM glucose, 2 mM
      pyruvate medium at a constant beating rate (6 Hz) and temperature (37 degrees C),
      were subjected to changes in work load by varying the calcium concentration
      ([Ca2+]) in the perfusion fluid from 0.5 to 1.0, 1.5, or 2.0 mM. Each change in
      left ventricular developed pressure (LVDP) induced by the [Ca2+] change was
      accompanied by alterations in the inorganic phosphate-to-creatine phosphate ratio
      ([Pi]/[PCr]), with the ATP level remaining constant. The relationship between
      [Pi]/[PCr] and LVDP followed a Michaelis-Menten pattern with an apparent
      Michaelis constant (Km) of 0.09 and a maximal LVDP of 91 mmHg. This Km
      corresponded to intracellular concentrations of 1.2 mM for Pi and 13.0 mM for
      PCr. The calculated [ADP] and phosphorylation potential corresponding to these
      values were 44 microM and 151,000 M-1, respectively. All these values are close
      to those estimated under in situ physiological conditions. These results support
      the assumption that in the rat heart, as in skeletal muscle, mitochondrial
      activity could be controlled by changes in phosphorylated compound concentrations
      under normoxic conditions.

PMID- 1992788
TI  - Contrasting preganglionic and postganglionic effects of phenylephrine on
      parasympathetic control of heart rate.
AB  - Previous reports indicate that alpha-adrenergic agonists modulate vagal control
      of heart rate. In the rat, phenylephrine inhibition of vagal-stimulated
      bradycardia may be occurring at any of a number of sites along the cardiac
      parasympathetic pathway. The purpose of the present experiments was to localize
      the pre- or postganglionic sites of phenylephrine modulation of parasympathetic
      mediated bradycardia in the rat. Sprague-Dawley rats were anesthetized and
      instrumented with arterial and venous catheters and electrocardiographic leads.
      The cervical vagi were sectioned, and propranolol was administered. The right
      cervical vagus nerve was electrically stimulated to activate preganglionic
      parasympathetic nerves. Carbachol was injected to activate nicotinic receptors on
      postganglionic parasympathetic nerves (i.e., intracardiac ganglion cells).
      Methacholine was injected to activate muscarinic receptors at the sinoatrial
      node. The heart rate responses to these three interventions were recorded before,
      during, and after phenylephrine infusion. Phenylephrine significantly attenuated
      the bradycardia produced by vagal nerve stimulation. In contrast, phenylephrine
      facilitated the bradycardia elicited by carbachol injection. Since carbachol has
      both muscarinic and nicotinic effects, the results were compared with those
      obtained from methacholine, a pure muscarinic agonist. Phenylephrine had no
      effect on methacholine-induced bradycardia, suggesting that the modulation of the
      carbachol response was through carbachol's nicotinic effects. Yohimbine, the
      alpha 2-receptor antagonist, eliminated phenylephrine-mediated facilitation of
      the carbachol response. These data indicate that phenylephrine has contrasting
      effects on pre- and postganglionic cardiac parasympathetic nerves in rats:
      inhibition at preganglionic sites (vagal stimulation results) and facilitation at
      the level of the ganglion cells (carbachol experiments).

PMID- 1992789
TI  - Cytochemical studies of hydrogen peroxide generation in postischemic hepatocytes.
AB  - Reoxygenation injury that occurs when blood circulation is restored to previously
      ischemic tissues is currently discussed as a pathophysiological entity distinct
      from the primary anoxic injury that develops during ischemia per se. To test the
      hypothesis that reoxygenation injury in hepatocytes is caused by a postischemic
      burst of reactive oxygen species (ROS), including superoxide radicals, O2-., and
      hydrogen peroxide, H2O2, we performed a cytochemical study exploiting the
      peroxidase activity within peroxisomes as a sensitive ultrastructural detector of
      intracellular H2O2 generation. The osmiophilic polymer formed when tissue
      peroxidase is incubated with 3,3'-diaminobenzidine (DAB) and H2O2 was used as a
      marker for endogenous H2O2 in rat liver slices in short-term organ culture
      subjected to a cycle of 60-min ischemic anoxia and 30-min reoxygenation in the
      presence of DAB without exogenous H2O2. Peroxisomal reaction product was
      quantitatively evaluated in transmission electron micrographs of systematically
      sampled hepatocytes. Mean densities of positive peroxisomes per 1,000 micron2 (+/
      SE) in liver slices subjected to various treatments were as follows: continuous
      anoxia (negative control) 0 +/- 0; normoxia + exogenous H2O2 (positive control)
      45 +/- 12; normoxia only 26 +/- 2; ischemia-reoxygenation 13 +/- 6; ischemia
      reoxygenation + xanthine oxidase inhibitor, oxypurinol 5 +/- 3; ischemia
      reoxygenation + peroxidase inhibitor, aminotriazole 7 +/- 3. Endogenous H2O2 can
      be detected in hepatocytes by electron microscopic cytochemistry and may in part
      derive from xanthine oxidase, but it is not substantially increased in the
      postischemic state. We conclude that hepatocytes do not exhibit a postischemic
      burst of reactive oxygen species that could cause reoxygenation injury.

PMID- 1992790
TI  - Importance of endothelium-derived nitric oxide in porcine coronary resistance
      arteries.
AB  - Endothelial cells regulate vascular tone through the release of nitric oxide and
      other relaxing factors. The role of these substances was studied in isolated
      intramyocardial porcine coronary resistance arteries suspended in myographs for
      isometric tension recording. The inhibitor of nitric oxide formation NG
      monomethyl-L-arginine (L-NMMA; 10(-7)-10(-4)M), but not D-NMMA, caused
      endothelium-dependent contractions that could be reversed by L-arginine but not
      by D-arginine. In preparations with endothelium, L-NMMA potentiated the
      contractions induced by acetylcholine and the relaxations to 3-morpholino
      sydnonimine. Under both conditions, the effect of endothelial removal was
      slightly more pronounced than that of L-NMMA. Bradykinin, serotonin, and the
      alpha 2-adrenergic agonist clonidine evoked endothelium-dependent relaxations. L
      NMMA as well as the inhibitor of guanylate cyclase methylene blue (10(-5) M)
      prevented the relaxations induced by clonidine, reduced those to serotonin, but
      hardly affected those to bradykinin. Thus, in porcine coronary resistance
      arteries, endothelium-derived nitric oxide is continuously produced from L
      arginine. Endothelium-dependent relaxations to clonidine are fully mediated and
      those to serotonin partially mediated by nitric oxide; its release does not
      involve a Gi protein. An endothelium-derived relaxing factor different from
      nitric oxide must mediate the relaxations to bradykinin and contribute to those
      evoked by serotonin.

PMID- 1992791
TI  - Endothelial independence of myogenic response in isolated skeletal muscle
      arterioles.
AB  - The goal of this study was to determine whether the endothelium played a role in
      the myogenic response of skeletal muscle arterioles. First-order arterioles (n =
      15) were isolated from the rat cremaster muscle and cannulated for in vitro
      study. The development of spontaneous tone reduced the diameter of the isolated
      arterioles from 166.7 +/- 7.6 microns to 89.2 +/- 7.2 microns. The arterioles
      were exposed to step changes in intraluminal pressure over a range of 10-170
      cmH2O and had no flow through their lumen. The vessels exhibited active
      constriction to step increases or active dilation to step decreases in pressure
      (50-150 cmH2O). At 90 cmH2O, arterioles dilated by 89.2 +/- 6.0% in response to
      the endothelium-dependent vasodilator acetylcholine (10(-6) M; ACh) and 89.6 +/-
      10.9% in response to endothelium-independent dilator adenosine (10(-4) M; Ado).
      The endothelium was physically denuded by rubbing the vessel lumen. After
      denudation, the arteriolar dilation to ACh was abolished, whereas the dilation to
      Ado was unaltered. The absence of endothelium was verified by electron
      microscopy. Basal tone and the response to changes in pressure were not
      significantly different from endothelium-intact vessels. These studies indicate
      that the endothelium is not responsible for myogenic activity or development of
      spontaneous tone in skeletal muscle arterioles.

PMID- 1992792
TI  - Impaired myocardial function in spontaneously hypertensive rats with heart
      failure.
AB  - We have observed that many spontaneously hypertensive rats (SHR) between the ages
      of 18 and 24 mo develop findings suggestive of heart failure, including pleural
      and pericardial effusions, left atrial thrombi, and right ventricular
      hypertrophy. Isolated left ventricular papillary muscle function was studied in
      these animals (SHR-F), in age-matched SHRs without evidence of heart failure (SHR
      NF), and in nonhypertensive controls (WKY). Preparations from SHR-F showed
      depression of active tension development (3.58 +/- 1.75 g/mm2, means +/- SD)
      compared with both SHR-NF (7.17 +/- 0.94) and WKY (6.17 +/- 1.00) (P less than
      0.01). Shortening velocity was also depressed in SHR-F (0.95 +/- 0.38 lengths/s)
      compared with SHR-NF (1.60 +/- 0.30; P less than 0.05) and WKY groups (2.15 %/-
      0.48; P less than 0.01). Depression of muscle function was not found before 18 mo
      of age. Thus the aging SHR is a model in which one can observe the transition
      from chronic stable left ventricular hypertrophy to overt heart failure.
      Furthermore, left ventricular papillary muscles from SHRs with heart failure show
      evidence of significant contractile dysfunction, suggesting that impairment of
      intrinsic myocardial function underlies the development of heart failure.

PMID- 1992793
TI  - Hemodynamic consequences of ventricular interaction as assessed by model
      analysis.
AB  - Because of close anatomic association, the pressure and volume in one ventricle
      can directly influence the pressure and volume in the opposite ventricle. To
      examine the importance of ventricular interdependence in controlling the
      circulation, we developed a computer model in which ventricular interdependence
      could be turned on and off. Left ventricular chamber contractility, as judged by
      maximal elastance (Emax), was enhanced on the order of 10% as a result of
      ventricular interaction, whereas right ventricular Emax was affected by as much
      as 60% under physiological conditions. With increases in systemic vascular
      resistance, ventricular interaction caused a smaller stroke volume (SV) decrease
      than with no interaction. For canine data (SV = 21.4 ml), doubling systemic
      vascular resistance decreased SV by 3.7 without ventricular interdependence, 3.5
      with diastolic ventricular interdependence, and 3.3 ml with diastolic and
      systolic ventricular interdependence. In contrast, with increases in pulmonary
      vascular resistance, ventricular interaction caused a greater decrease in SV than
      with no interaction present. Decreasing left ventricular free wall elastance or
      right ventricular free wall elastance decreased SV. Diastolic ventricular
      interdependence reduced the SV changes, whereas systolic ventricular
      interdependence accentuated the SV changes with alterations in right and left
      ventricular free-wall elastance. The results of the present simulation
      demonstrate the importance of ventricular interdependence in the observed
      responses of the right ventricle to volume overload, pressure overload, and
      ischemia.

PMID- 1992794
TI  - Position of interventricular septum during heart cycle in anesthetized dogs.
AB  - The impact of the transseptal pressure gradient (TSP) during the entire heart
      cycle has not been assessed. This study explores in anesthetized open-chest dogs
      the interventricular septum's relative position to the anteroposterior transverse
      diameter (Dap) of the left ventricle (LV). By varying preload and afterload for
      both LV and right ventricle (RV) and inotropy in LV, a wide range of TSP was
      generated. By ultrasonomicrometry the distance between the Dap and the midpoint
      of septum was recorded. 1) Loops of the septal-LV free-wall diameter vs. Dap
      showed that the LV transverse cross section independent of loading conditions
      tended to reach a circular form during systole. 2) Paradoxical movement of the
      intraventricular septum occurred when TSP was less than zero but was not
      dependent on an increase of TSP. 3) TSP's influence on septum's position was
      reduced to one-tenth when changing from end diastole to end systole. 4) During
      systole independent of level of LV performance, LV pressure had approximately 50%
      less influence on septal position than RV pressure. 5) During depressed LV
      performance a similar pattern was evident during diastole. 6) The pericardium had
      no influence on septum's position. This study demonstrates that the position of
      the intraventricular septum is significantly influenced by the time-varying
      elastance of LV and the septum itself, and that RV pressure changes have a
      greater impact on septal position than LV pressure changes.

PMID- 1992795
TI  - Metabolic correlates of adenosine formation in stimulated guinea pig heart.
AB  - Adenosine release into epicardial fluid and coronary effluent of isolated
      isovolumic guinea pig hearts was examined at baseline and after stimulation with
      norepinephrine (30 nM) during 31P-nuclear magnetic resonance spectroscopy to
      monitor myocardial metabolism. At baseline flow (9.6 +/- 0.3 ml.min-1.g-1),
      epicardial and venous adenosine concentrations were 154 +/- 40 and 17 +/- 5 nM,
      respectively. The phosphorylation potential (log[ATP]/[ADP][Pi]) and the
      phosphocreatine-inorganic phosphate ratio ([PCr]/[Pi]) were 5.26 +/- 0.04 and 8.5
      +/- 0.7, respectively. Norepinephrine increased left ventricular pressure, heart
      rate, and myocardial O2 consumption rate by approximately 21, 70, and 45%,
      respectively, and increased epicardial and venous adenosine to 496 +/- 74 and 461
      +/- 94 nM, respectively. Log-[ATP]/[ADP][Pi] and [PCr]/[Pi] declined to 4.57 +/-
      0.06 and 1.9 +/- 0.3, respectively. Epicardial [AMP] increased from 54 +/- 13 to
      123 +/- 24 nM. AMP was not detectable in the venous effluent. Coronary resistance
      correlated with epicardial and venous [adenosine] (r = 0.86 and 0.90). Epicardial
      and venous [adenosine] correlated with log[ATP]/[ADP][Pi], [PCr]/[Pi], and
      cytosolic [AMP]. Hence, interstitial adenosine is linked to cytosolic metabolism
      and may regulate coronary vascular resistance. Venous adenosine underestimates
      epicardial adenosine at baseline but more closely approximates epicardial
      adenosine during norepinephrine infusion.

PMID- 1992797
TI  - Adenosine antagonism decreases metabolic but not functional recovery from
      ischemia.
AB  - The effect of adenosine receptor antagonism on function and metabolism was
      examined in isolated hearts during low flow ischemia and reperfusion. Isovolumic
      rat hearts perfused at constant flow were subjected to 30 min of ischemia
      followed by 30 min of reperfusion. Infusion of vehicle or 10 microM 8
      phenyltheophylline (8-PT) was initiated 10 min before ischemia and maintained
      throughout reperfusion. 8-PT infusion had no significant effects on hemodynamic
      parameters or metabolism preischemia. During ischemia, left ventricular developed
      pressure declined to approximately 15% of preischemic values in control and 8-PT
      hearts, and ATP and PCr decreased to approximately 73 and 60% of preischemic
      values. Inorganic phosphate (Pi) increased to 353 = 41 and 424 +/- 53% of
      preischemic values in control and 8-PT hearts, respectively. After reperfusion,
      function recovered to greater than 95% of preischemic levels in control and 8-PT
      hearts. Unlike control hearts, recovery of metabolites was significantly
      different during reperfusion in 8-PT hearts (P less than 0.05); ATP,
      phosphocreatine, and Pi recovered to 82 +/- 8, 71 +/- 8, and 281 +/- 27% of
      preischemic values, respectively. Venous purine washout was significantly greater
      (P less than 0.05) during reperfusion in 8-PT hearts (327 +/- 113 nmol) than in
      control hearts (127 +/- 28 nmol). Blockade of adenosine receptors appears to
      adversely affect metabolic but not functional recovery in the ischemic-reperfused
      myocardium.

PMID- 1992796
TI  - Reduced exercise capacity in senescent beagles: an evaluation of the periphery.
AB  - This study investigated the effect of age on peripheral factors involved in the
      systemic response to maximal exercise. Skeletal muscle was analyzed and regional
      blood flow distribution was determined at rest and during maximal exercise in
      senescent (old) and in younger mature (young) beagles. Maximal exercise capacity
      was significantly reduced (P less than 0.05) in old and was associated with a
      reduction in cardiac output (CO), as well as a tendency for arteriovenous O2
      difference to be reduced, with a concomitant reduction in maximal O2 consumption.
      In each regional circulation evaluated, resting blood flow was similar in young
      and old. During exercise, blood flow was similar in young and old to the
      diaphragm, heart, tongue, and six of seven locomotory muscles. Concomitant blood
      flow reductions in splanchnic regions tended to be more pronounced in old than in
      young. Skeletal muscle analyses of triceps, semitendinosus, and gastrocnemius
      muscles disclosed similar percent fiber type distribution in young and old but a
      reduction in type II fiber area in old. In addition, both muscle capillary
      density and capillary-to-fiber ratio were reduced in old. These results
      demonstrate that age-related changes in blood flow distribution during maximal
      exercise enable skeletal muscle blood flow to be maintained in old, despite
      reductions in maximal CO and in muscle capillary density. However, this pattern
      of blood flow distribution only partially compensates for the combined effects of
      age-related changes in metabolic potential of the periphery, O2 content of
      arterial blood, and cardiac function during maximal exercise in old.

PMID- 1992798
TI  - Vascular factors in isovolumic systemic and pulmonary circuit.
AB  - Experiments were conducted in 12 pentobarbital-anesthetized dogs with sinus
      denervation and vagotomy. The chest was opened, and the heart was replaced by a
      roller pump with two perfusion lines. The systemic and pulmonary circulations (SC
      and PC) were perfused with a constant and adjustable flow (Q). Venous outflows
      were directly driven by pumps without passing through a reservoir. In each closed
      circuit, the total blood volume remained constant because inflow and outflow were
      simultaneously and equally altered. In both SC and PC, arterial pressure (Pa),
      i.e., systemic arterial and pulmonary arterial pressures (SAP and PAP), was a
      positive function of Q, and venous pressure (Pv), i.e., right atrial and left
      atrial pressures (RAP and LAP), was a negative function of Q. The first series of
      experiments involved three equal step reductions in Q from baseline to zero flow.
      The venous-to-arterial compliance ratio (Cv/Ca) was calculated from delta
      Pa/delta Pv and vascular resistance (VR) from (Pa - Pv)/Q. The values of Cv/Ca in
      SC increased from 9.3 +/- 0.4 to 14.5 +/- 1.1 and 21.9 +/- 1.4 (P less than
      0.001) in the three-step Q reduction. VR in the SC was not significantly
      dependent on Q. In the PC, the Cv/Ca was approximately 2.0 and VR was 0.16
      mmHg.ml-1.min.kg, both values being independent of Q. Multiple-step reduction in
      Q for regression equations was carried out in 8 of the 12 dogs. We found that
      only the SAP was a linear function of Q (ml.min-1.kg-1): SAP = 18.458 +
      0.953Q.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1992799
TI  - Effect of adrenal hypotension on elicited secretory activity in anesthetized
      dogs.
AB  - The objective of this study was to determine whether three- to fourfold increases
      in adrenal medullary blood flow (MQ), observed during catecholamine secretion
      induced by splanchnic nerve stimulation (NS), are necessary for a maximal
      secretory response. Eight pentobarbital-anesthetized adult male mongrel dogs (25
      35 kg) were subjected to two episodes of NS-induced catecholamine secretion. To
      limit increases in MQ, one NS (20 Hz, 8 V, 1.5 ms) was performed under control
      conditions, the other was after reduction of adrenal perfusion pressure (PP). PP
      was 124.8 +/- 6.0 at control and was reduced to 23.0 +/- 1.0 mmHg by inflation of
      an aortic occluder located 3 in. above the adrenals. NS under control conditions
      increased ipsilateral MQ (measured using radiolabeled microspheres) from 181 +/-
      39 to 1,336 +/- 199 ml.min-1.100 g-1 and adrenal epinephrine secretion from 184
      +/- 128 to 11,445 +/- 5,216 ng.min-1.g medulla-1. Contralateral MQ and cortical
      blood flow were unaffected by NS. Reduction of PP decreased MQ to 32 +/- 6 ml.min
      1.100 g-1 and adrenal cortical blood flow from 251 +/- 23 to 25 +/- 6 ml.min
      1.100 g-1.PP reduction had no effect on either corticosteroid secretion or
      unstimulated epinephrine secretion. NS at reduced PP increased ipsilateral MQ to
      146 +/- 27 ml.min-1.100 g-1 and epinephrine secretion to 13,935 +/- 5,175 ng.min
      1.g medulla-1. These data indicate that epinephrine secretion is not altered when
      MQ is limited by reduction of PP and suggest that, at normal PP, increases in MQ
      during catecholamine secretion are not necessary for a maximal secretory
      response.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1992800
TI  - DNA synthesis in isolated arteries. Kinetics and structural consequences.
AB  - We evaluated changes in DNA synthesis, structure, and mechanical activity in
      isolated arteries during exposure to growth factors. Renal arteries were isolated
      from rats, sympathectomized, denuded of endothelium, and maintained in tissue
      culture. Up to 4 days of culture did not affect maximal contractile responses to
      depolarization. From the results of nuclear incorporation of the thymidine
      analogue 5-bromo-2-deoxyuridine (BrdUrd), culture stimulated DNA synthesis. In
      the media, incorporation of BrdUrd was maximal after 3 days but fell
      precipitously thereafter. Culture of arterial segments did not, however, increase
      the cross-sectional area of the media, the ploidy of the arterial nuclei, or the
      number of medial cells. In contrast, new layers of cells, part of which displayed
      smooth musclelike properties, developed at the border of the segments. The
      outermost edge of this newly formed layer continued to incorporate BrdUrd for at
      least 2 wk. These data demonstrate that stimulation of DNA synthesis by
      continuous exposure of the arterial wall to exogenous growth factors is 1)
      transient in the media; 2) does not, at least initially, compromise contractile
      reactivity; 3) does not alter gross medial structure; but 4) leads to
      proliferation of smooth musclelike cells outside the media. These findings
      suggest that the number of smooth muscle cells in the arterial media is
      maintained constant in the presence of even strong mitogenic stimuli.

PMID- 1992801
TI  - Central nervous system histamine regulates peripheral sympathetic activity.
AB  - Brain histamine (HA) was depleted in conscious Sprague-Dawley rats by central
      administration of alpha-fluoromethyl-histidine (alpha-FMH), an irreversible
      inhibitor of the HA synthesizing enzyme. Isotonic or hypertonic saline was
      infused intravenously at 10 microliters.100 g-1.min-1 for 30 min and mean
      arterial pressure (MAP) and heart rate (HR) were monitored. In addition, plasma
      vasopressin (AVP) and norepinephrine (NE) were measured pre- and postinfusion.
      Animals pretreated with alpha-FMH showed a delayed and attenuated pressor
      response and bradycardia during hypertonic saline (HTS) infusion and a
      significant reduction in plasma NE levels (-29 +/- 8% below control values).
      However, plasma concentrations of AVP were similar in both groups. Central
      pretreatment with the H1-antagonist pyrilamine (PYR) also delayed the onset and
      significantly attenuated the pressor response to HTS infusion, and caused dose
      related decreases in plasma NE concentrations (-34 +/- 8, -47 +/- 5, and -52 +/-
      7% after 60, 100, and 600 nmol PYR, respectively). These data indicate a role for
      central HA in peripheral sympathetic activation but not as a mediator of AVP
      release to a peripheral hyperosmotic stimulus.

PMID- 1992802
TI  - Cellular mechanisms of delayed recovery of excitability in ventricular tissue.
AB  - It is well established that ventricular tissue, under some conditions, exhibits
      the phenomenon of postrepolarization refractoriness (PRR) in which the tissue
      excitability is depressed after an action potential. We have done parallel
      experiments on rabbit papillary muscles and on isolated rabbit ventricular cells
      to explain the cellular basis of this phenomenon, using elevated extracellular K+
      concentration ([K+]o) (8 mM) to depolarize the tissue and the isolated cells. For
      isolated cells, we could separately measure cellular excitability (the inverse of
      the cellular current threshold) and the cellular responsiveness (the ability of
      the cell to generate inward current after excitation has occurred). We present
      two hypotheses that could explain the magnitude and time course of tissue PRR in
      terms of either changes in cellular excitability or changes in cellular
      responsiveness. We show that, although small changes in cellular excitability do
      occur, the predominant cellular mechanism for tissue PRR is the time course of
      recovery of the cellular responsiveness.

PMID- 1992803
TI  - Mechanical properties of adult feline ventricular myocytes in culture.
AB  - The contractile and electrophysiological properties of cultured adult feline
      ventricular myocytes were studied. Cells were field stimulated and contraction
      was measured using a video-based edge detector. The magnitude of contraction
      decreased by 36% and the rate of contraction decreased by 52% 2 h after the cells
      were plated on laminin-coated cover slips. The magnitude and rate of contraction
      then remained stable for 1 wk. The duration of contraction prolonged and a second
      component to the twitch frequently, but not invariably, developed after 5 days in
      culture. This was associated with prolongation of the action potential duration.
      After 7 days in culture, cells could be divided into two groups based on resting
      membrane potential. Norepinephrine increased the magnitude of contraction for 5
      days after plating. Cultured ventricular myocytes became unresponsive to the
      effects of norepinephrine after 7 days. Adult cardiac myocytes maintained in
      primary culture continue to respond to field stimulation and retain many
      contractile properties for up to 7 days; however, the functional characteristics
      of these cells do not remain uniform during this time period.

PMID- 1992804
TI  - Carotid baroreceptor control of liver and spleen volume in cats.
AB  - We tested the hypothesis that the blood volumes of the spleen and liver of cats
      are reflexly controlled by the carotid sinus (CS) baroreceptors. In pentobarbital
      anesthetized cats the CS area was isolated and perfused so that intracarotid
      pressure (Pcs) could be controlled while maintaining a normal brain blood
      perfusion. The volume changes of the liver and spleen were estimated by measuring
      their thickness using ultrasonic techniques. Cardiac output, systemic arterial
      blood pressure (Psa), central venous pressure, central blood volume, total
      peripheral resistance, and heart rate were also measured. In vagotomized cats,
      increasing Pcs by 100 mmHg caused a significant reduction in Psa (-67.8%),
      cardiac output (-26.6%), total peripheral resistance (-49.5%), and heart rate (
      15%) and significantly increased spleen volume (9.7%, corresponding to a 2.1 +/-
      0.5 mm increase in thickness). The liver volume decreased, but only by 1.6% (0.6
      +/- 0.2 mm decrease in thickness), a change opposite that observed in the spleen.
      The changes in cardiovascular variables and in spleen volume suggest that the
      animals had functioning reflexes. These results indicate that in pentobarbital
      anesthetized cats the carotid baroreceptors affect the volume of the spleen but
      not the liver and suggest that, although the spleen has an active role in the
      control of arterial blood pressure in the cat, the liver does not.

PMID- 1992805
TI  - Effects of fetal anemia on PO2 difference between uterine venous and umbilical
      venous blood.
AB  - In the fetus, the functional equivalent of the alveolar-arterial blood PO2
      difference is the uterine venous-umbilical venous blood PO2 difference.
      Generally, factors that affect one of the venous blood PO2s produce equivalent
      effects on the other. We previously showed that fetal anemia produces increases
      in umbilical venous blood PO2. To determine whether this increase was associated
      either with equivalent increases in uterine venous blood PO2 or with reductions
      in the uterine venous-umbilical venous PO2 difference, we studied eight
      chronically catheterized pregnant sheep and fetal lambs. Measurements of O2 gas
      tensions and O2 saturations, uterine and umbilical blood flows, and uterine,
      fetal, and placental O2 consumptions were made in animals with normal fetal
      hematocrits and during reductions in fetal hematocrit of 35% (moderate fetal
      anemia) or 60% (severe fetal anemia). Fetal anemia produced reductions in the
      uterine venous-umbilical venous blood PO2 difference; in some cases the PO2
      difference was less than 2 mmHg (compared with normal values of 20 mmHg). The
      development of both moderate and severe fetal anemia had no effect on uterine and
      umbilical blood flows or placental O2 consumption but did reduce total uterine
      and fetal O2 consumption. These data indicate that fetal anemia induces changes
      in placental gas transport. These changes may be due to improvements in gas
      diffusion, reductions in perfusion mismatching, or reductions in vascular
      shunting. Our data further indicate that placental O2 consumption rate, which is
      high in normal pregnant sheep, plays no role in the maintenance of the uterine
      venous-umbilical venous blood PO2 difference in pregnant sheep.

PMID- 1992806
TI  - Theoretical study of pressure-volume relation in left ventricle.
AB  - The myocardium is represented as a thick-walled elastic cylinder contracting
      symmetrically. The concept of body force (force/unit volume) is used to model the
      force developed by the myocardium in the radial direction during systolic
      contraction. It is shown that the radial force per unit area developed by the
      myocardium on its inner surface can be included in the equation describing the
      pressure-volume relation in the left ventricle. Application of the equations
      derived to experimental data describing the pressure-volume line in the Suga
      Sagawa model is given. The results obtained seem to indicate that the body force
      developed by the myocardium in a normal ejecting contraction reaches its peak
      toward the end of the contraction phase and that the peak value is related to the
      peak isovolumic pressure when a quasistatic approximation of the systolic
      contraction is considered. Implication of the developed model for future studies
      in cardiac mechanics is also discussed.

PMID- 1992807
TI  - Multicompartment model for mechanics and energetics of fibrillating ventricle.
AB  - We propose a new mechanical model of a fibrillating ventricle to interrelate
      ventricular mechanics and energetics during fibrillation. The model consists of
      multiple asynchronously contracting compartments with identical time-varying
      elastances but with different contraction phase lags. Pressures in all
      compartments are common, and volumes of all compartments change, keeping their
      sum constant in the model. We evaluated the mechanical behavior of each
      compartment by simulating this model on a personal computer. Results showed that
      each compartment contracts quasi-isobarically. We calculated the pressure-volume
      area (PVAc) of each compartment as a measure of the total mechanical energy
      generated by a contraction of the compartment. We found that the sum of PVAcs of
      all compartments agreed with the area (equivalent PVA; ePVA) surrounded by the
      end-systolic and end-diastolic pressure-volume relations and the isobaric line at
      the mean pressure of the fibrillating ventricle. We conclude that ePVA represents
      the total mechanical energy of the fibrillating ventricle model. The
      multicompartment model is useful for insight into the interrelation between
      ventricular mechanics and energetics during ventricular fibrillation.

PMID- 1992808
TI  - New technique to completely isolate carotid sinus baroreceptor regions in rats.
AB  - We developed a method by which we can completely isolate the carotid sinus
      baroreceptor regions in the rat. The carotid sinus baroreceptor region is exposed
      and, with the use of extra-fine forceps, a human hair is placed around and tied
      at the root of the bifurcation. This procedure occludes the external carotid
      artery and blood flow to the carotid body. An injector is then attached to a
      catheter in the common carotid artery. We introduce a cylindrical rubber plug
      into either the palentine or internal carotid artery. A second plug is introduced
      to occlude the other artery. In six of the eight rats studied, these procedures
      completely isolated the carotid sinus region. In those cases where a small leak
      persisted at a carotid sinus pressure of 180 mmHg, we introduced a small particle
      of the animal's own previously clotted blood. Carotid sinus pressure was either
      randomly changed between 40 and 180 mmHg in 20-mmHg increments or in sequential
      20-mmHg steps from 40 to 180 mmHg while measuring the animal's pulsatile and mean
      blood pressures. Arterial pressure-carotid sinus pressure relationship indicates
      that there is a highly sigmoidal relationship between the two pressures. The peak
      gain of the carotid sinus reflex system had a range from 1.5 to 4.0 and a mean
      value of 2.07 +/- 0.08. Our data indicate that the rat exhibits a significant
      carotid sinus baroreceptor reflex response. This technique combined with other
      techniques will allow for the study of neural control of cardiovascular function
      in the rat.

PMID- 1992810
TI  - NMR-visible ATP and Pi in normoxic and reperfused rat hearts: a quantitative
      study.
AB  - Nuclear magnetic resonance (NMR) spectroscopy detects only free, unbound
      metabolites. We have therefore compared the free high-energy phosphate content of
      isolated perfused rat hearts (determined by 31P-NMR) with the total high-energy
      phosphates of the same hearts (determined by chemical analysis) to determine the
      fractions, if any, that are NMR invisible. Aerobic perfusion (40 min at 37
      degrees C, Pi-free Krebs buffer) was followed by 10, 14, or 18 min total global
      ischemia and 30 min reperfusion (n = 6 in each group). Fully relaxed 31P-NMR
      spectra (40 scans using 90 degrees pulses at 15-s intervals) were collected at
      various times throughout the protocol, and the signal intensities of the beta
      phosphate of ATP, phosphocreatine (PCr), and Pi were quantified using
      methylenediphosphonate as an external standard. Hearts were freeze clamped either
      before ischemia or at the end of reperfusion and were chemically assayed for ATP,
      PCr, and Pi. After 40 min of normoxia, the ATP and PCr contents determined by NMR
      were almost identical to the values determined by chemical analysis. However,
      only 39 +/- 8% of the total Pi was NMR visible. After reperfusion, after 14 or 18
      min of ischemia, the proportion of NMR-visible ATP had decreased to 64 +/- 9% (P
      less than 0.005). After reperfusion after 18 min ischemia, the proportion of NMR
      visible Pi had increased to 76 +/- 10% (P less than 0.05). In conclusion, whereas
      the total cellular content of PCr is always NMR visible, ischemia-reperfusion can
      alter the fraction of NMR-visible ATP and Pi.

PMID- 1992809
TI  - Baroreflex-induced vasoconstriction in active skeletal muscle of conscious dogs.
AB  - We investigated the magnitude of baroreflex-mediated vasoconstriction in the
      hindlimbs of six conscious dogs at rest and during four levels of treadmill
      exercise ranging in intensity from mild (2 mph, 0% grade) to heavy (6 mph, 10%
      grade). Dogs were instrumented with vascular occluders on both common carotid
      arteries, an electromagnetic flow probe and vascular occluder on the terminal
      aorta, and a catheter in a branch of the femoral artery; aortic baroreceptors
      were intact. The responses to a 2-min carotid occlusion were observed at rest and
      after 3-5 min of exercise at each work rate. The increases in mean arterial
      pressure during carotid occlusion were similar at rest and at each level of
      exercise (26 +/- 4 to 35 +/- 3 mmHg; no significant difference). At rest, carotid
      occlusion caused only a small but significant decrease in terminal aortic
      vascular conductance (TAC) (-0.89 +/- 0.21 ml.min-1.mmHg-1, P less than 0.05).
      During mild exercise, baseline terminal aortic blood flow (TAQ) and TAC
      increased, and the reduction in TAC during carotid occlusion exceeded that
      observed at rest (-1.85 +/- 0.42 ml.min-1.mmHg-1, P less than 0.05). As exercise
      intensity increased, the magnitude of the reduction in TAC during carotid
      occlusion increased linearly with the baseline TAQ. At the highest work rate,
      approximately 59% of the increase in mean arterial pressure during carotid
      occlusion was due to the large decrease in TAC (-6.35 +/- 0.50 ml.min-1.mmHg-1).
      We conclude that the vasoconstriction of active skeletal muscle during the
      pressor response to bilateral carotid occlusion increased with exercise
      intensity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1992811
TI  - Paradox of enhanced contractility in postischemic rat hearts with depressed
      function.
AB  - Depressed function of postischemic hearts may be related to incomplete recovery
      of coronary perfusion. To circumvent this factor we studied the properties of
      papillary muscles under controlled extracellular conditions. First, recovery of
      function was measured in postischemic rat hearts. Next, a muscle was dissected
      and superfused in a bath. After 40 min of ischemia, recovery of cardiac output
      was generally zero. Muscles from this group were relaxed or showed small
      contractures. After 20-30 min of ischemia recovery of coronary flow and cardiac
      output was 50-100%, and the isolated muscles showed the following properties
      (compared with Langendorff-perfused controls): 1) increased force at normal or
      low [Ca2+]; 2) action potential and postextrasystolic potentiation were
      unchanged, which indicates that Ca2+ influx per beat was unchanged; 3) the decay
      of potentiation was slowed, indicating a reduced rate of Ca2+ extrusion via Na(+)
      Ca2+ exchange. This implies intracellular Ca2+ accumulation and explains the
      increased force. Postischemic enhancement of contractility (isovolumic pressure)
      was demonstrated also in whole heart preparations. We conclude that mild injury
      by preceding ischemia leads to enhanced contractility (Ca2+ accumulation),
      advanced injury to local contractures, and finally to a general contracture (Ca2+
      overload). Recovery of heart function and coronary flow probably depends on the
      number and size of local contractures.

PMID- 1992812
TI  - Comparative effects of hypoxia on behavioral thermoregulation in rats, hamsters,
      and mice.
AB  - Recent studies using reptiles and other ectothermic species have shown that
      hypoxia lowers the set point for the control of body temperature. This is
      characterized by a preference for cooler ambient (Ta) and deep body temperatures
      (Tb) when placed in a temperature gradient. To elucidate the presence of this
      effect in mammals, the selected Ta and Tb of three rodent species (mouse,
      hamster, and rat) were measured while subjected to graded hypoxia in a
      temperature gradient. Individual animals were placed in the gradient for 30 min.
      Oxygen content of air entering the gradient was then reduced to a constant level
      for a period of 60 min by dilution with nitrogen. Tb was significantly reduced in
      all species at %O2 levels of 5.5-10%. Selected Ta was significantly reduced in
      the mouse at %O2 levels of 5.5 and 7.3%. Selected Ta of the hamster and rat were
      reduced slightly at %O2 levels of 5.8 and 7.4%, respectively; however, the effect
      was not statistically significant. To clarify the effects of hypoxia in these two
      species, the sample size of rat and hamster was increased to strengthen
      statistical analysis, and the animals were exposed for 60 min to %O2 levels of
      7.4 and 6.7%, respectively. Both species exhibited a significant reduction in
      selected Ta during hypoxia concomitant with hypothermia. These data support the
      hypothesis that hypoxia lowers the set point for the control of body temperature
      in rodents.

PMID- 1992813
TI  - Macrophages produce somnogenic and pyrogenic muramyl peptides during digestion of
      staphylococci.
AB  - Muramyl peptides have a variety of biological effects in mammals, including
      enhancement of the immune response, sleep, and body temperature. Although mammals
      lack biosynthetic pathways for muramyl peptides, they are found in mammals and
      are well known as components of bacterial cell walls. This suggests that
      phagocytic mammalian cells digest bacterial cell walls and produce biologically
      active muramyl peptides. Staphylococcal cell walls were radioactively labeled
      during growth of the bacteria. During the digestion of these radiolabeled
      bacteria, murine bone marrow macrophages produced low-molecular-weight substances
      that coeluted chromatographically with the radioactive cell wall marker. Further
      separation of these substances using reversed-phase high-performance liquid
      chromatography resulted in the isolation of substances with high specific
      biological activity. Intracerebroventricular injection of rabbits with these
      substances induced an increase in slow-wave sleep and body temperature and a
      suppression of rapid-eye-movement sleep. The characteristics of the biological
      responses and the chromatographic behavior of the active components are
      consistent with those of muramyl peptides. The ability of macrophages to tailor
      muramyl peptides from peptidoglycan may provide an amplification step for the
      immune response. Muramyl peptides released by macrophages may also act as
      mediators for various facets of the acute phase response elicited by bacterial
      infections such as fever and sleep.

PMID- 1992814
TI  - Kinetic analysis of zinc metabolism in humans after simultaneous administration
      of 65Zn and 70Zn.
AB  - Zinc kinetics were studied and compared after oral simultaneous administration of
      two tracers, radioactive (65Zn) and stable (70Zn) isotope, to four normal human
      volunteers. Both tracers and zinc concentration were measured in plasma, red
      blood cells (RBC), urine, and feces for up to 78 days. Radioactive zinc was also
      measured by external counting over whole body, liver, and thigh. Data from each
      individual were analyzed using a compartmental model for zinc metabolism. Values
      calculated for absorption, fractional zinc excretion in urine, exchange with RBC,
      and secretion into gut using 70Zn data did not differ from values calculated
      using 65Zn data. Results show that human zinc metabolism can be investigated
      using stable isotopes as tracers to determine parameters of whole body zinc
      metabolism, including zinc absorption, excretion, and secretion.

PMID- 1992815
TI  - Insulin-induced anestrus in Syrian hamsters.
AB  - In Syrian hamsters, reproduction is sensitive to the availability of metabolic
      fuels. Estrous cycles can be interrupted by brief periods of food deprivation, by
      pharmacological inhibition of glycolysis and fatty acid oxidation, or by
      increasing energy demands for thermoregulation. We predicted that manipulations
      that divert an excessive portion of the metabolic fuel supply into storage also
      should inhibit reproduction. Redirection of metabolic fuels from oxidation to
      storage was accomplished by treatment with protamine zinc insulin suspension
      (PZI). Syrian hamsters treated with PZI and fed ad libitum increased their food
      intake by approximately equal to 40% and body fat stores, but there was no effect
      on estrous cycles. When PZI-treated hamsters were limited to approximately equal
      to 110% of their preinjection food intake, they still fattened, and there was a
      significant inhibition of estrous cyclicity. Thus, in the absence of overeating,
      PZI-enhanced energy storage may lead to a shortage of oxidizable metabolic fuels
      with the result that reproduction is inhibited in favor of processes essential
      for survival (e.g., cellular maintenance, thermoregulation). It is unlikely that
      insulin-induced anestrus is due to actions of PZI unrelated to metabolic fuel
      partitioning, because the hormone had no effects on estrous cyclicity in ad
      libitum-fed hamsters. These findings are inconsistent with the hypothesis that
      nutritional infertility is due to the failure to maintain a minimum body fat
      content and raise the possibility that the infertility associated with some types
      of obesity could be due in part to a disorder of macronutrient partitioning.

PMID- 1992816
TI  - Effects of pregnancy and ovarian steroids on fatty acid synthesis and uptake in
      Syrian hamsters.
AB  - The effects of pregnancy and ovarian steroids on the in vivo distribution of
      newly synthesized fatty acids (incorporation of tritium from 3H2O into fatty
      acid) in Syrian hamsters (Mesocricetus auratus) were examined. During late, but
      not early, gestation hamsters had reduced levels of newly synthesized fatty acids
      in heart, liver, uterus, and white adipose tissues (parametrial and inguinal fat
      pads). Treatment of ovariectomized hamsters with estradiol + progesterone
      significantly decreased fatty acid synthesis-uptake in heart, liver, and inguinal
      white adipose tissue. Treatment with either estradiol or progesterone alone was
      without significant effect in any tissue. Pretreatment of hamsters with Triton WR
      1339 (tyloxapol), an inhibitor of lipoprotein lipase activity and tissue
      triglyceride uptake, abolished the effects of estradiol + progesterone in white
      adipose tissue and heart but not in liver. Thus hamsters lose body fat during
      pregnancy in part because of decreased de novo lipogenesis. The effect of
      pregnancy on lipogenesis is mimicked by treatment with estradiol + progesterone
      but not by either hormone alone. Furthermore, it appears that the liver is the
      principal site of estradiol + progesterone action on lipogenesis in Syrian
      hamsters.

PMID- 1992818
TI  - Contribution of brain distortion and displacement to CSF dynamics in experimental
      brain compression.
AB  - The present study was designed to determine the contribution of brain distortion
      and displacement to changes in cerebrospinal fluid (CSF) dynamics [pressure
      volume index (PVI), compliance (C), and outflow resistance (Ro)] during
      progressive brain compression and the effect of compression on brain mechanical
      properties. In 10 dogs measurements were made of CSF dynamics, brain elastic
      behavior, cerebral perfusion pressure, local cerebral blood flow, and
      suprainfratentorial intracranial pressure (ICP) during the incremental expansion
      of a supratentorial extradural balloon. PVI appeared more as a measure of the
      compressibility of the cerebral vascular compartment than of intracranial bulk
      compliance. Reciprocal changes in CSF dynamics behaved as expected when the
      balloon expanded predominantly supratentorially causing a moderate increase in
      ICP. A significant increase in ICP, however, caused a rise in PVI and a decrease
      in compliance. Under these conditions PVI alone could not differentiate between a
      falling cerebral perfusion pressure and an increasing suprainfratentorial ICP
      gradient. In contrast, the compliance decreased with balloon expansion while the
      outflow resistance showed an inverse correlation with compliance and a linear
      correlation with baseline ICP; Go, an elastic response parameter, consistently
      decreased, implying that C, Ro, and Go can be used as a trend of intracranial
      compensatory reserve during intracranial mass expansion.

PMID- 1992817
TI  - Differential alterations in plasma IL-6 and TNF levels after trauma and
      hemorrhage.
AB  - Tumor necrosis factor (TNF) and interleukin 6 (IL-6) are purported to be
      important mediators of inflammatory responses. It is not known whether the plasma
      levels of these cytokines are altered after trauma and hemorrhage. Our objectives
      were to determine whether there is any elevation of plasma TNF or IL-6 after
      trauma and hemorrhage and to what extent these changes are due to tissue trauma
      vs. simple hemorrhage. Trauma was induced in Sprague-Dawley rats under light
      ether anesthesia by performing a 5-cm midline laparotomy. On closure, animals
      were catheterized, awakened, hemorrhaged to a mean blood pressure of 40 mmHg, and
      maintained at that pressure until 40% of maximum shed blood volume was returned
      in the form of Ringer lactate (RL). Animals were then resuscitated with RL
      equivalent to four times shed blood volume. Blood samples (0.5 ml) were taken
      before inducing hemorrhage, at maximal bleed out (45 min), and at 4 and 6 h
      posthemorrhage to obtain plasma. IL-6 and TNF levels were measured using cytokine
      dependent cellular assays. TNF levels were significantly elevated at 45 min into
      hemorrhage and remained so up to 4 h after hemorrhage. IL-6 levels were also
      elevated 45 min into hemorrhage and remained so up to 6 h posthemorrhage. IL-6,
      unlike TNF, was already significantly increased after midline laparotomy and
      before initiation of hemorrhage compared with unmanipulated animals. Thus
      induction of IL-6 by trauma may be partially independent of those mechanisms in
      hemorrhage that are involved in the release of TNF.

PMID- 1992819
TI  - Cholecystokinin conditions flavor preferences in rats.
AB  - The present study investigated whether cholecystokinin (CCK), an intestinal
      hormone that is a putative satiety agent, can condition flavor preference in
      rats. In experiment 1 food-deprived rats were trained to consume two different
      flavored saccharin solutions in separate one-bottle tests. One flavor (the CS+)
      was paired with intraperitoneal injections of CCK octapeptide (0.125-4
      micrograms/kg); the other flavor was paired with intraperitoneal injections of
      saline. Flavor preferences were then assessed in subsequent two-bottle choice
      tests. The 0.125 and 0.25 micrograms/kg doses failed to suppress CS+ intake or
      produce flavor preferences. CCK at 0.5 micrograms/kg did not reliably suppress
      CS+ intake in the one-bottle tests but produced a reliable preference for the CS+
      in the two-bottle tests; percent CS+ intakes ranged from 50 to 62% in the four
      preference tests. At 1 microgram/kg, CCK suppressed CS+ intake and produced a
      marginal preference for the CS+. The 2 micrograms/kg dose suppressed CS+ intake
      but failed to condition a CS+ preference. The 4 micrograms/kg dose of CCK
      produced a potent suppression of CS+ intake and a strong aversion to that flavor.
      The preference conditioning effect of CCK at 0.5 microgram/kg was replicated in a
      second experiment using flavored Polycose solutions. The finding that low doses
      of CCK condition flavor preferences in rats is compatible with the hypothesis
      that endogenous CCK can mediate satiety and further suggests a role for CCK in
      learned food preferences. The aversion conditioned by the highest dose of CCK
      does not detract from this interpretation, since food, if consumed in excess, can
      also have aversive consequences.

PMID- 1992820
TI  - Topography of efferent vagal innervation of the rat gastrointestinal tract.
AB  - The gastrointestinal territories innervated by the gastric, celiac, and hepatic
      abdominal vagi were identified in rats with selective branch vagotomies by means
      of 1) anterograde tracing with the carbocyanine dye DiI injected into the dorsal
      motor nucleus and 2) measurement of cervical vagal stimulation-induced motility
      responses throughout the gut axis. Presence of DiI-labeled vagal terminals in the
      myenteric plexus and evoked motility responses were well correlated across the
      sampled gastrointestinal (GI) sites. In animals with only the two gastric
      branches intact, the entire stomach and the most proximal duodenum showed
      significant motility responses and were densely innervated, having DiI-labeled
      vagal terminals in almost every ganglion. The hepatic branch was found to
      primarily innervate the duodenum, with minor projections to the distal antral
      stomach and the intestines. The two celiac branches were found to almost
      exclusively innervate the jejunum, ileum, cecum and entire colon, and, together
      with the other vagal branches, the duodenum. Therefore, while there is some
      degree of specific innervation by the abdominal vagal branches of the oral-to
      anal gut axis, which could be called "viscerotopic," the considerably overlapping
      innervation of the duodenum does not satisfy a viscerotopy criterion and needs
      further functional analysis.

PMID- 1992821
TI  - High-potassium diet attenuates salt-induced acceleration of hypertension in SHR.
AB  - We studied the effects of K supplementation (8% KCl) for 4 wk on blood pressure
      (BP), Na space, and renal hemodynamics in 5-wk-old, spontaneously hypertensive
      rats (SHR) or age-matched Wistar-Kyoto rats (WKY) eating normal-NaCl (0.66%) or
      high-NaCl (8%) diet. In WKY, high-Na and/or high-K diets had no effects on BP. In
      SHR, Na load accelerated the development of hypertension, whereas K
      supplementation did not affect BP of normal-Na SHR but attenuated the increase in
      BP with Na load. Correspondingly, Na load in SHR significantly increased renal
      vascular resistance (RVR), and K supplementation attenuated the increased RVR of
      Na-loaded SHR. Moreover, Na space of SHR was increased compared with that of WKY,
      and although Na load did not affect Na space, K supplementation tended to
      decrease Na space in SHR. These results indicate that 9-wk-old SHR is relatively
      volume-expanded compared with age-matched WKY, and K supplementation could
      improve the lowered slope of the pressure-Na excretion relationship in SHR,
      resulting in maintenance of Na balance. Thus the data suggest that changes in
      RVR, which might be intimately related to renal function for Na excretion,
      contribute to both salt sensitivity of SHR and antihypertensive action of K
      supplementation in Na-loaded SHR.

PMID- 1992823
TI  - Central arterial hemodynamics in larval bullfrogs (Rana catesbeiana):
      developmental and seasonal influences.
AB  - Central arterial hemodynamics (blood pressure and velocity) as a function of
      ontogeny and season were determined in larval Rana catesbeiana (body mass 0.3-8.7
      g, 20-22 degrees C). Ventricular systolic pressure increased from 1.8 mmHg at
      stage (St) II to 11.9 mmHg at St XIII, while ventricular diastolic pressures
      usually were less than 1.0 mmHg. In early stages (up to St V-VII) of fall/winter
      larvae, the pressure waveform in the conus arteriosus was often biphasic. The
      first peak was due to weak ventricular contraction (sometimes inadequate to eject
      blood into the arterial tree), and a stronger second peak resulted from conal
      contraction. In these young fall/winter larvae, the conus--not the ventricle--was
      the major circulatory pump. Older larvae (greater than St X) showed "adultlike"
      central hemodynamics, with the ventricle ejecting blood through the conus into
      the central arterial circulation. Systolic blood pressure was considerably higher
      in young spring/summer (April-June) larvae, and the ventricle rather than the
      conus was the main circulatory pump at all stages, in contrast to fall/winter
      larvae. Thus both season and development have profound influences on the central
      hemodynamics of bullfrog larvae.

PMID- 1992822
TI  - Cardiovascular influences on rat parabrachial nucleus: an electrophysiological
      study.
AB  - The rat pontine parabrachial nucleus is a prominent recipient of autonomic
      related information from the more caudal levels of the neuraxis. The present
      experiments examined the responsiveness of neurons within the parabrachial
      nucleus to the following three specific cardiovascular stimuli: the activation of
      peripheral arterial baroreceptors, right atrial stretch receptors, and the
      administration of systemic angiotensin (ANG) II. Extracellular recordings in
      urethan-anesthetized animals indicate the presence of cells, mostly within the
      lateral parabrachial nucleus, that increase (17.5%, 28 of 160 cells) and decrease
      (48.1%, 77 of 160 cells) their excitability consequent to baroreceptor
      activation. A similar profile of alteration in cellular firing rates was observed
      with intravenous ANG II (increase in 15.8%, 16 of 101 cells; decrease in 28.7%,
      29 of 101 cells). In contrast, fewer neurons located within the medial
      parabrachial and the Kolliker-Fuse nuclei were activated by these stimuli. A
      majority of cells (80%, n = 15) displayed a lack of response to right atrial
      stretch receptor activation. Of ANG II-sensitive lateral parabrachial cells, 23%
      (n = 43) revealed an alteration in excitability that could not be explained on
      the basis of a response to elevation in blood pressure. It is possible that this
      group of cells may be activated by the actions of systemic ANG II on neurons of
      the area postrema, a circumventricular structure, whose central projections are
      directed toward the parabrachial nucleus. These findings also support the notion
      of a diversity of cardiovascular inputs to topographically segregated regions
      within the parabrachial nucleus.

PMID- 1992824
TI  - Characteristics of facial nerve-elicited cerebral vasodilatation determined using
      laser Doppler flowmetry.
AB  - Cerebral cortical perfusion was monitored continuously with laser Doppler
      flowmetry and quantitative measurements of cerebral blood flow performed with the
      freely diffusible tracer 4-iodo[N-methyl-14C]antipyrine in the alpha-chloralose
      anesthetized cat. The facial nerve was isolated from the brain stem via a
      posterior fossa craniotomy and electrically stimulated at frequencies of 1, 2, 5,
      10, and 20 s-1. A stimulus-locked frequency-dependent increase in cerebral
      perfusion was seen in the parietal cortex; the mean maximum increase was 91 +/-
      22% at 20 s-1. This compared with an absolute flow of 116 +/- 3 ml.100 g-1.min-1
      at the same site. In addition, the response was associated with a marked increase
      in cerebral venous O2 content indicating that it is a primary neurogenic dilator
      response. This response could be blocked by hexamethonium but not by atropine and
      was thus mediated by an autonomic ganglion but not by the classical muscarinic
      postsynaptic receptor. Sectioning of the facial nerve did not alter
      cerebrovascular reactivity to hypercapnia. These data confirm the vasodilator
      effect of activation of the facial nerve and document its mediation through an
      intermediate parasympathetic ganglion. Consistent with previous data, the facial
      nerve does not appear to play a role in hypercapnic cerebral vasodilatation.
      Furthermore, this study highlights the usefulness of laser Doppler flowmetry in
      the cerebral circulation and in particular in the setting where repeated measures
      are required, such as in pharmacological studies.

PMID- 1992825
TI  - Responses of spinoreticular cells to graded increases in renal venous pressure.
AB  - Previous work established that occlusion of the renal vein excites spinoreticular
      tract (SRT) neurons of the cat. The present study was designed to determine the
      relationship between renal vein pressure level and SRT cell activity. Experiments
      were performed on 40 cats that were anesthetized with alpha-chloralose. Sixty SRT
      neurons in the T12-L2 segments were tested for responses to a renal vein pressure
      (RVP) of 60 mmHg. Twenty-three cells responded with an increase in activity.
      Stimulus response relationship for these cells were determined over the RVP range
      of 10-80 mmHg. RVP thresholds averaged 25 +/- 3 mmHg. Above this level greater
      increases in RVP were associated with greater increases in neuronal activity. At
      RVP of 80 mmHg cell activity increased from 4 +/- 2 to 21 +/- 5 spikes/s. Cells
      with both A delta- and C-fiber renal afferent inputs had significantly greater
      responses and lower thresholds than cells with only A delta input. Renal vein
      occlusion evoked increases in blood pressure. At a renal vein pressure of 80
      mmHg, pressor responses averaged 16 +/- 5 mmHg. No significant changes in heart
      rate were observed. The results demonstrate that SRT cells are capable of
      encoding the level of RVP. Such responses may be important for grading of
      reflexes of renal origin that require supraspinal circuitry.

PMID- 1992826
TI  - Hemodynamic responses to acute volume expansion in Dahl salt-sensitive rats.
AB  - The purpose of this study is to evaluate hemodynamic responses to acute volume
      expansion in chronically instrumented, conscious Dahl salt-sensitive (Dahl-S) and
      Dahl salt-resistant (Dahl-R) rats that have been maintained on either 0.45% NaCl,
      1% NaCl, or 7% NaCl (5 days) intakes. Total peripheral resistance (TPR), but not
      arterial pressure, was increased by 5 days of 7% NaCl in Dahl-S (P less than
      0.05) but not in Dahl-R. In Dahl-S, but not in Dahl-R, right atrial pressure
      increased with increasing dietary NaCl (P less than 0.05). On the 0.45% NaCl
      intake, atrial pressure did not differ in the two strains, whereas on both the 1
      and 7% NaCl diets atrial pressure was higher in Dahl-S than in Dahl-R (P less
      than 0.05). In response to acute extracellular fluid volume expansion, arterial
      pressure did not change, and cardiac output increased in Dahl-S and in Dahl-R. On
      the 0.45% NaCl intake, TPR decreased (P less than 0.01) similarly in response to
      volume expansion in both strains; however, on the 1% NaCl intake TPR decreased in
      Dahl-R (P less than 0.05) but not in Dahl-S. In contrast, in animals fed 7% NaCl
      for 5 days, TPR decreased acutely in Dahl-S (P less than 0.01) but not in Dahl-R.
      These observations suggest that cardiopulmonary baroreflex activity is impaired
      in Dahl-S on a 1% NaCl intake, possibly as a consequence of elevated right atrial
      pressure. This alteration of the cardiopulmonary baroreflex may contribute to
      increased TPR in Dahl-S on a high-NaCl intake.

PMID- 1992827
TI  - Role of sympathetic nerves in effects of estradiol on rat white adipose tissue.
AB  - Two experiments examined the role of the sympathetic nerves in estradiol-induced
      fat pad weight losses in ovariectomized (OVX) rats. Rats were OVX, and the
      retroperitoneal white adipose tissue (RWAT) was unilaterally denervated 4 wk
      later. After 14 days of treatment with estradiol benzoate (EB, 2 micrograms/day),
      the intact pads lost 23% more weight than the denervated pads. There was no
      effect of denervation on fat pad weight or on cytosol estrogen receptor
      concentration in RWAT in the animals treated with sesame oil vehicle. These data
      suggest that the sympathetic nerves play a role in estrogen-induced reductions in
      fat pad weight but not via changes in adipose tissue cytosol estrogen receptors.
      A second experiment examined whether estradiol-induced fat pad weight losses are
      accompanied by increased norepinephrine (NE) turnover, an index of sympathetic
      activity, in adipose tissue. Rats were OVX and treated with EB or sesame oil
      vehicle. NE turnover was assessed by measuring the decline of tissue NE over time
      after injection of alpha-methyl-p-tyrosine, an inhibitor of tyrosine hydroxylase
      activity and thus NE biosynthesis. NE turnover in RWAT, but not heart, was
      significantly greater in animals treated with EB, suggesting that estradiol
      decreases fat pad weight in part by increasing sympathetic nervous system
      activity. It is possible that estradiol acts in the brain to regulate the
      activity of the sympathetic nerves to white adipose tissue and peripherally to
      alter adipose tissue responsiveness to catecholamines.

PMID- 1992828
TI  - Interleukin 1 alters rat sleep: temporal and dose-related effects.
AB  - Rats received various doses of interleukin 1 (IL-1) (range, 0.5-25.0 ng) or
      pyrogen-free saline intracerebroventricularly during the rest (light) and the
      active (dark) cycles of the day, and sleep-wake activity and brain temperature
      were determined for 6 h. Low doses of IL-1 (0.5 ng at night, 2.5 ng during the
      day) increased both the duration of non-rapid-eye-movement sleep (NREMS) and
      electroencephalogram (EEG) slow-wave activity during NREMS episodes. Increasing
      doses of IL-1 had divergent effects on NREMS duration and EEG slow-wave activity,
      and the direction of the changes depended on the diurnal cycle. Thus NREMS
      duration was promoted at night and EEG slow-wave amplitudes during the day,
      whereas NREMS duration during the day and EEG slow-wave amplitudes at night were
      suppressed after higher doses of IL-1. High doses of IL-1 also induced decreases
      in rapid-eye-movement sleep during both phases of the day. Each dose of IL-1 that
      promoted NREMS also tended to increase brain temperature. These results
      demonstrate that IL-1 promotes NREMS in the rat. However, unlike previously
      reported findings in rabbits, the circadian rhythm of sleep regulation strongly
      interferes with the sleep-promoting activity of IL-1 in rats.

PMID- 1992829
TI  - Contribution of brown adipose tissue to central PGE1-evoked hyperthermia in rats.
AB  - The relative contribution of several effector systems to a prostaglandin E1
      (PGE1) evoked hyperthermia was examined. Infusion of 150 ng of PGE1 into a
      lateral cerebral ventricle increased core temperature and whole body metabolic
      rate, brown adipose tissue temperature, systolic blood pressure, and heart rate.
      Pretreating the animals with a nonselective beta-antagonist propranolol (1 mg/kg
      iv in 0.3 ml followed by 3 mg.kg-1.h-1 in 0.3 ml/h) not only attenuated the rise
      in metabolism observed after the central administration of 150 ng PGE1 but also
      diminished the elevation in both core and brown fat tissue temperatures as well
      as the increase in heart rate. Pretreating the animals with the alpha-antagonist
      prazosin (2 mg/kg im followed by 50 micrograms.kg-1.h-1 iv in 0.3 ml/h) somewhat
      reduced the rise in whole body metabolism, suppressed the elevation in core
      temperature, but failed to alter the rise in brown adipose tissue temperature
      normally seen after the central administration of PGE1. Moreover, both the rise
      in systolic blood pressure and heart rate were attenuated when the PGE1
      administration was preceded by prazosin. These results suggest that brown adipose
      tissue is an important effector organ responsible for mediating the hyperthermic
      response observed after the intracerebral injection of PGE1. In addition, the
      results indicate that alterations in vasomotor tone may also be important in
      producing or sustaining the elevated core temperature found after a pyrogen
      administration.

PMID- 1992830
TI  - Effect of hepatic vagotomy on hormonal response to exercise in gluconeogenesis
      inhibited rats.
AB  - The liver, through the afferent pathway of the hepatic vagus nerve, has been
      reported to influence the hormonal response to exercise in adrenodemedullated
      rats. The present investigation was designed to evaluate the role played by
      gluconeogenesis in this hepatic influence. To this end, we studied the effects of
      a selective hepatic vagotomy on the hormonal response to a 30-min treadmill run
      (26 m/min, 0% grade) in adrenodemedullated rats injected with 3-mercaptopicolinic
      acid, a gluconeogenic inhibitor. Hepatic vagotomy was associated with small but
      significant higher (P less than 0.05) elevations of peripheral blood glucose
      levels at rest and after exercise. No significant differences were observed
      between hepatic-vagotomized and sham-operated rats in either resting or
      exercising levels of liver glycogen, portal glucose, portal and peripheral
      insulin and glucagon, and peripheral epinephrine and norepinephrine. All hormonal
      responses, with the exception of epinephrine, were either decreased or increased
      similarly in the two experimental conditions after exercise. These data indicate
      that contrary to what has been reported in rats with an intact capacity for
      gluconeogenesis, hepatic-vagotomized and sham-operated rats with an inhibited
      gluconeogenesis had similar hormonal responses to exercise. It is concluded that
      gluconeogenesis plays a role in the afferent neural influence exerted by the
      liver via the hepatic vagus nerve in the regulation of hormonal response to
      exercise.

PMID- 1992831
TI  - Genetics and psychiatry: an unheralded window on the environment.
AB  - Two recent reviews in the American Journal of Psychiatry and the British Journal
      of Psychiatry reported on progress in understanding the genetics of psychiatric
      disorder. Both reviews focused on this progress as a prelude to psychiatric
      diagnostics and therapeutics based on molecular biology. Neither review
      recognized that the latest data in behavioral genetics support environmental
      causes for abnormal development and psychopathology as much as they support
      genetic causes. Moreover, these genetic data point clearly to a type of
      environmental cause with central importance: the environment that is specific or
      unique to each sibling in a family.

PMID- 1992832
TI  - Substance abuse and cerebral blood flow.
AB  - OBJECTIVE AND METHOD: This paper reviews acute and chronic effects of drugs of
      abuse on cerebral blood flow (CBF) and metabolism and their clinical
      significance. The most important source of information for the review is human
      research reports published in refereed journals. A few animal studies, book
      chapters, and abstracts that are especially relevant are also included. RESULTS:
      In humans, ethanol in small doses produces cerebral vasodilation; higher doses
      induce cerebral vasoconstriction. Chronic alcoholism is associated with reduced
      CBF and cerebral metabolism. Sedatives and antianxiety drugs lead to global
      reduction in CBF and cerebral metabolism. Caffeine, even in small doses, is a
      potent cerebral vasoconstrictor. Cerebral vasodilation is seen immediately after
      cigarette smoking, but chronic smokers show global reduction in CBF. Changes in
      CBF after marijuana smoking are variable; both increases and decreases are seen.
      Chronic marijuana smoking, however, seems to reduce CBF. Most inhalants and
      solvents are vasodilators; chronic abuse is accompanied by a decrease in CBF. A
      number of drugs of abuse, including ethanol, amphetamines, cocaine, nicotine, and
      caffeine-phenylpropanolamine combinations, increase the risk for stroke.
      Reduction in CBF associated with chronic use of ethanol, nicotine, inhalants, and
      solvents is at least partially reversible upon abstinence. CONCLUSIONS: Topics
      for future research include regional brain function, which mediates drug-induced
      mood changes (euphoria); CBF concomitants of psychological and physiological
      characteristics that increase addiction potential; changes in CBF that accompany
      withdrawal syndromes; mechanisms responsible for drug-induced stroke; and effects
      of functional and organic complications on CBF.

PMID- 1992833
TI  - A psychodynamic perspective on the clinical impact of insurance review.
AB  - The rise of managed care and concurrent utilization review has had a profound
      impact on the practice of inpatient psychiatry. Little has been written, however,
      on the clinical impact of the review process itself. The actions of insurance
      reviewers often result in their being incorporated into the psychopathology of
      individual patients and into the dynamics of families and institutional settings.
      The authors apply psychodynamic understanding to a series of case examples to
      illustrate how concurrent review may promote splitting, impede the patient's
      ability to separate from the hospital, and paradoxically reinforce the patient's
      illness. They also explore a number of typical responses of treatment staff and
      families to the review process. A case vignette demonstrating a sincere effort at
      mutual collaboration between payers and providers is also presented. This spirit
      of compromise is proposed as the solution that best serves patient care.

PMID- 1992834
TI  - Psychological comorbidity and length of stay in the general hospital.
AB  - OBJECTIVE: As general hospitals search for ways to cut costs without sacrificing
      efficiency, particular attention has been focused on factors that may prolong
      hospital stay. The results of prior studies that have reported an association
      between psychological and psychiatric comorbidity and longer hospital stays have
      been subject to different interpretations because of methodological design flaws.
      The current paper reports on a study of psychological comorbidity and length of
      stay that has been designed to avoid the methodological problems of earlier
      investigations. METHOD: The study was performed at a 429-bed tertiary-care,
      university-affiliated, voluntary, teaching hospital. During hospital days 3 to 5,
      patients were tested as available with the Mini-Mental State examination, the
      Zung Depression Inventory, and the SCL-90 and were rated for physical impairment
      with the Karnofsky Performance Status Scale. Statistical analyses were performed
      for correlations between length of stay and test scores, rating scales, and
      demographic and discharge data from the chart. RESULTS: Of 424 patients
      approached, 321 (76%) agreed to participate and 278 (65.6%) completed the test
      battery. Depression, anxiety, and organicity, measured by psychological tests,
      were significantly correlated with longer hospital stay. These correlations
      remained significant after the authors controlled for degree of physical
      impairment, emergency versus elective admission, and medical versus surgical
      service, which were themselves correlated with longer hospital stay. DISCUSSION:
      This study confirms a significant correlation between psychological comorbidity
      and length of stay after correcting for the methodological pitfalls found in
      earlier studies. The clinical, research, economic, and policy implications of
      these findings are discussed.

PMID- 1992835
TI  - Housing instability and homelessness among rural schizophrenic patients.
AB  - OBJECTIVE: The authors examined housing instability among treated schizophrenic
      patients in a rural area and compared the findings with those from their previous
      study of urban patients. METHOD: Seventy-five patients with schizophrenia or
      schizoaffective disorder who were treated in a rural mental health center were
      assessed with research interviews and ratings by their clinical case managers.
      The patients were followed for 1 year to identify episodes of psychiatric
      hospitalization, incarceration, and literal homelessness. RESULTS: Of the 75
      patients, 19 (25%) had housing situations characterized as unstable by their case
      managers. For the majority, housing instability signified tenuousness of living
      arrangements rather than literal homelessness. Noncompliance with medications,
      alcohol use, and negative symptoms accounted for 30% of the variance in unstable
      housing. During follow-up, the unstably housed patients, compared to those in
      stable living situations, were no more likely to be rehospitalized but were
      somewhat more likely to be jailed and significantly more likely to be literally
      homeless. CONCLUSIONS: In the authors' previous study of urban psychiatric
      patients, unstably housed patients were more likely to be literally homeless,
      highly symptomatic, and rehospitalized during follow-up than the rural patients
      with unstable housing. Better outcomes in the rural area appeared to be related
      to the greater availability of housing alternatives and to intensive case
      management. For patients with unstable housing in both settings, noncompliance
      with medications and substance abuse, as well as housing arrangements, should be
      assertively addressed.

PMID- 1992837
TI  - 12-month outcome of patients with major depression and comorbid psychiatric or
      medical illness (compound depression).
AB  - OBJECTIVE: Inpatients with major depressive illness often have coexistent
      nonaffective psychiatric and/or medical conditions. The authors' objective is to
      address the following questions: 1) What is the effect of comorbid illness on the
      severity of major depression and associated psychosocial factors? 2) How does the
      course of depression differ for patients with and without concurrent illness? 3)
      Do patients with compound depression differ in rate of recovery and time to
      recovery from patients with pure depression? METHOD: The subjects were 78
      patients with a DSM-III diagnosis of major depression who were consecutively
      admitted to an acute care university-affiliated psychiatric hospital; 37 of these
      patients had major depression only and 41 had major depression compounded by a
      coexisting axis I, II, or III condition. The patients were studied while
      hospitalized and for 12 months after hospital discharge. Instruments used
      included the Modified Hamilton Rating Scale for Depression, the Global Assessment
      Scale, and the Social Readjustment Rating Scale. RESULTS: Patients with compound
      depression reported significantly poorer functioning over the 12-month follow-up
      period and had lower recovery rates than the patients with pure depression. There
      were no differences in recovery rates between men and women with compound
      depression, but significantly more men than women with pure depression recovered.
      CONCLUSIONS: Compound depression is a common clinical occurrence, the course of
      illness is more difficult for patients with compound depression than for patients
      with pure depression, and the recovery rate of patients with compound depression
      is lower than that of patients with pure depression.

PMID- 1992836
TI  - A critical appraisal of mitogen-induced lymphocyte proliferation in depressed
      patients.
AB  - OBJECTIVE: The authors' goal was to evaluate the utility of mitogen-induced
      lymphocyte proliferation assays in clinical research in psychoimmunology. METHOD:
      They examined 23 depressed patients and 23 matched comparison subjects with this
      assay. There were no significant differences between these groups. They then
      combined the results of this study with the results of their previous study of 20
      depressed patients and 20 comparison subjects to examine possible determinants of
      lymphocyte proliferation in depression. RESULTS: Depressed patients with lower
      proliferative responses than their matched comparison subjects had lower
      depression subscale, anergia subscale, and total scores on the Brief Psychiatric
      Rating Scale than did patients with higher proliferative responses than their
      matched comparison subjects. This finding was unexpected and unexplained.
      Depressed patients with lower proliferative responses than their matched
      comparison subjects also had fewer obsessions and compulsions and less
      psychomotor agitation according to the Schedule for Affective Disorders and
      Schizophrenia interview than did patients with higher proliferative responses
      than their matched comparison subjects. Stepwise discriminant analysis and
      cluster analysis contributed little further understanding of the determinants of
      in vitro lymphocyte proliferation of cells from depressed patients. CONCLUSIONS:
      Longitudinal studies using multiple serial determinations of mitogen-induced
      lymphocyte proliferation are the minimal design needed to make this assay useful
      in further evaluating any immune system changes in depression.

PMID- 1992838
TI  - Depressive symptoms following stroke.
AB  - OBJECTIVE: The primary purpose of this study was to assess the relation of lesion
      location to mood and vegetative disturbance following stroke. METHOD: Fifty-two
      inpatients and outpatients who had had single, unilateral strokes were included.
      Patients with past CNS or psychiatric disorders were excluded. A modified Visual
      Analogue Dysphoria Scale was used to allow the inclusion of all but the most
      impaired aphasic patients. Sleep and eating disturbances were measured by using
      both self-report and nursing assessments. Location of lesions was determined by
      CT scan and classified according to three dimensions: right-left, dorsal-ventral,
      and frontal-nonfrontal. RESULTS: On measures of dysphoric mood and sleep
      disturbance, results indicated significant three-way interactions among the three
      lesion dimensions. No differences were found with regard to eating disturbance.
      Greater dysphoria and sleep disturbance were found in subjects with left
      parietal/occipital, left inferior frontal, right superior frontal, and right
      temporal lesions than in subjects with lesions in other locations. Depressive
      symptoms were not associated with functional impairment as measured by activities
      of daily living, motor strength, or severity of aphasia. CONCLUSIONS: These
      results support the hypothesis that lesion location is a valid and significant
      factor in the mixture of influences which may result in a dysphoric mood state
      following stroke. The relation between the site of the lesion and subsequent
      depressive symptoms, however, may be more complex than has been reported
      previously.

PMID- 1992839
TI  - The nature and course of olfactory deficits in Alzheimer's disease.
AB  - OBJECTIVE: The aim of this study was to determine the specific nature and course
      of olfactory deficits in Alzheimer's disease. Previous studies had noted impaired
      odor identification, but there was no unanimity about the presence of odor
      detection deficits. METHOD: Odor identification was tested in 55 patients with
      Alzheimer's disease and 57 elderly control subjects by using the University of
      Pennsylvania Smell Identification Test. Odor detection was assessed in 46
      subjects with Alzheimer's disease and 40 control subjects by using a forced
      choice threshold test with geraniol as the odorant. RESULTS: Significant deficits
      in olfactory identification were present in subjects who were in the earliest
      stages of cognitive impairment, and these deficits increased as Alzheimer's
      disease progressed. There was some overlap in individual smell identification
      test scores between cognitively impaired patients and normal elderly subjects. On
      the other hand, odor detection deficits did not appear until Alzheimer's disease
      was relatively advanced. Smell identification test scores were correlated with
      Mini-Mental State scores, but geraniol detection was not. CONCLUSIONS: Odor
      identification is impaired early in Alzheimer's disease and may be more
      influenced by cognitive status than is acuity of odor detection, which is not
      altered until later in the disorder. The pattern of hyposmia in Alzheimer's
      disease suggests that the disorder may not "begin in the nose," as has been
      theorized previously. Further refinement of olfactory testing may be useful in
      the diagnostic evaluation of early dementia.

PMID- 1992840
TI  - Nonfearful panic disorder in neurology patients validated by lactate challenge.
AB  - OBJECTIVE: Nonfearful panic disorder meets the DSM-III-R criteria for panic
      disorder but is not associated with subjective fear and anxiety. The authors
      determined its prevalence in a group of neurology patients and assessed its
      diagnostic validity as a panic disorder subtype by evaluating the response of the
      patients with nonfearful panic disorder to sodium lactate and antipanic
      pharmacotherapy. METHOD: The subjects were all neurology patients referred over 1
      year to a university hospital's psychiatric consultation service because of
      negative medical workups for their symptoms (N = 48). Patients who met the DSM
      III-R criteria for panic disorder but did not report subjective anxiety or fear
      during panic episodes were diagnosed as having nonfearful panic disorder.
      Afterward, each of those patients received a sodium lactate infusion and, 5 hours
      later, a sodium chloride infusion. They were then treated with antipanic
      medication and followed for at least 6 months. RESULTS: Of the 48 neurology
      patients referred for psychiatric evaluation, 11 (23%) met the criteria for panic
      disorder, and all 11 met the criteria for nonfearful panic disorder. All 11
      responded positively to lactate but not to placebo, and they each experienced an
      at least 75% reduction in symptoms during the 6-month follow-up period. Detailed
      case reports of three of these patients are presented. CONCLUSIONS: These
      findings support the construct and predictive diagnostic validity of nonfearful
      panic disorder as a subtype of panic disorder and suggest that a lack of
      attention to this group leads to both the underestimation of the prevalence of
      panic disorder and to the withholding of potentially successful treatments for
      this group.

PMID- 1992842
TI  - Nortriptyline treatment of depressed cardiac transplant recipients.
AB  - The safety of tricyclic antidepressants in cardiac transplant recipients has not
      been established. The author used nortriptyline to treat major depressive
      episodes in eight cardiac transplant recipients. Nortriptyline therapy was
      associated with increased QRS interval and heart rate but did not significantly
      affect other hemodynamic or ECG variables or cyclosporine dose requirements. It
      appears that nortriptyline may be used safely in depressed cardiac transplant
      patients.

PMID- 1992841
TI  - Characteristics of 60 adult chronic hair pullers.
AB  - OBJECTIVE: This study was constructed to detail the demographic and
      phenomenological features of chronic hair pullers as well as to assess
      psychiatric comorbidity in a sizable study group. METHOD: Subjects were drawn
      from an outpatient population of chronic hair pullers who had been referred to a
      trichotillomania clinic or had responded to a newspaper advertisement announcing
      a treatment study of adults who pull out their hair. Sixty adult chronic hair
      pullers completed a semistructured interview that focused on their hair-pulling
      behavior and demographic characteristics and that incorporated screening
      questions for DSM-III-R axis I disorders. The data were tabulated to derive a
      comprehensive picture of this group. RESULTS: The typical subject was a 34-year
      old woman who had pulled hair from two or more sites for 21 years. All subjects
      described either tension before or relief/gratification after pulling hair from
      the primary site, but 17% (N = 10) failed to describe both of these
      characteristics and thus failed to fulfill the DMS-III-R criteria for
      trichotillomania. Forty-nine subjects (82%) qualified for past or current axis I
      diagnoses other than trichotillomania. Several characteristics of the study group
      suggested phenomenological differences between obsessive-compulsive disorder and
      trichotillomania. CONCLUSIONS: Adult trichotillomania is a chronic disorder,
      frequently involving multiple hair sites, and is associated with high rates of
      psychiatric comorbidity. Its relation to obsessive-compulsive disorder requires
      further clarification. The tension-reduction requirement in DSM-III-R for the
      diagnosis of trichotillomania may be overly restrictive.

PMID- 1992843
TI  - Transdermal nicotine and smoking behavior in psychiatric patients.
AB  - The authors used a double-blind crossover design to observe the effect of
      transdermally administered nicotine on the smoking behavior of 13 psychiatric
      patients who were not trying to stop smoking. The patients smoked significantly
      fewer cigarettes while receiving nicotine than while receiving placebo. These
      data suggest that transdermally administered nicotine can be a useful adjunct in
      treating nicotine-addicted psychiatric patients in a non-smoking environment.

PMID- 1992844
TI  - The Osheroff debate: finale.

PMID- 1992845
TI  - Unexpected intracerebral pathology in older schizophrenic patients.

PMID- 1992846
TI  - Safer use of MAOIs.

PMID- 1992847
TI  - Severe hair loss associated with fluoxetine use.

PMID- 1992848
TI  - Thyroid function and phototherapy in seasonal affective disorder.

PMID- 1992849
TI  - A variant of the syndrome of subjective doubles.

PMID- 1992850
TI  - Dissociation in endogenous psychosis.

PMID- 1992851
TI  - Organic mental disorders and DSM-IV.

PMID- 1992852
TI  - Plasma prolactin levels and cocaine abuse.

PMID- 1992853
TI  - Physical and sexual abuse histories of male psychiatric patients.

PMID- 1992854
TI  - Human atherosclerotic coronary artery xenografts: a model for investigation of
      transluminal recanalization.
AB  - A model for testing transluminal recanalization techniques was developed.
      Fragments of human atherosclerotic coronary arteries were transplanted into
      carotid arteries of dogs and evaluated by angiographic, angioscopic, and
      histologic study within a three-month period. An inflammatory response was most
      intense within the first week. By two weeks no inflammation was noted. Total
      occlusion (n = 13) and stenosis (n = 11) of the carotid arteries were achieved
      without complications. The model is easy to produce within a short period and the
      arterial occlusion resembles human vascular disease. This model has been used to
      evaluate laser recanalization of vascular obstructions.

PMID- 1992855
TI  - Treatment of angiomas with sclerosing injection of hydroxypolyethoxydodecan.
AB  - The authors discuss the indications for hydroxypolyethoxydodecan in the
      sclerosing treatment of angiomas, with particular reference to cavernous, venous,
      and evolutive angiomas (ie, immature angiomas that fail to involute by eight to
      ten months). Moreover, the sclerosing agent may be employed, in connection with
      embolization and subsequent surgery, in arteriovenous angiomas with a relevant
      cutaneous-subcutaneous development. The authors have successfully used the
      "interstitial" sclerosing technique, according to Andrews' method. This technique
      involves interstitial injections to obtain the sclerosis of the thin threads of
      fibrous tissue stroma between the blood vessels. The sclerosing therapy may cause
      the complete regression of "low flow" angiomas or, at least, a partial reduction
      that simplifies the ensuing surgical excision. In the case of partial regression
      of the angioma obtained with the sclerosing therapy, the surgery of the remaining
      angioma causes a lesser degree of bleeding (especially in areas that do not
      particularly lend themselves to surgical exploration, ie, the oral cavity); an
      increased reliability in the radicality of the intervention (due also to the
      reduced size of the lesion); and better results from an aesthetic-functional
      point of view.

PMID- 1992856
TI  - ST segment alternans during percutaneous transluminal coronary angioplasty--a
      case report.
AB  - The occurrence of electrical alternans of the ST segment has been reported in
      patients with variant angina. The authors encountered a patient with typical
      electrical alternans of the ST segment in leads V4 through V6, which developed
      during percutaneous transluminal coronary angioplasty (PTCA) of the proximal left
      anterior descending artery. Hemodynamic pulsus alternans of the aortic pressure
      tracing was not observed during electrical alternans, and a Ca2+ blocker could
      not prevent this phenomenon during PTCA.

PMID- 1992857
TI  - Neuropeptide Y- and vasoactive intestinal polypeptide-containing nerve fibers in
      the human cerebral arteries: characteristics of distribution.
AB  - Perivascular innervation in cerebral arteries from 28 human fetuses at twelve to
      twenty-eight weeks' gestational age was studied histochemically. Neuropeptide Y
      (NPY)- and vasoactive intestinal polypeptide (VIP)- containing nerve fibers were
      densely distributed along with adrenergic and cholinergic nerve fibers in the
      major pial arteries at the base of the brain, an area that forms the circle of
      Willis, and in the lenticulostriate arteries. In contrast, distribution was
      sparse in the cortical circumflex branches of the middle cerebral artery, as
      compared with findings in the lenticulostriate artery of the same diameter.
      Densely distributed perivascular nerve fibers in the lenticulostriate arteries
      may play an important role in the pathogenesis of intracerebral hemorrhage.

PMID- 1992858
TI  - Coronary artery aneurysm without stenosis in association with Osler-Weber-Rendu
      disease--a case report.
AB  - A fifty-three-year-old woman presented with coronary artery aneurysm in
      association with Osler-Weber-Rendu disease (hereditary hemorrhagic
      telangiectasia) manifested also by large pulmonary arteriovenous fistulas. The
      arterial dye dilution curves were unusually distorted owing to the right-to-left
      shunts. The coronary artery aneurysm was located in multiple sites but was not
      accompanied by stenotic lesions. Coronary artery aneurysm without stenosis is a
      rare pathologic state and has not been previously reported in association with
      hereditary telangiectasia.

PMID- 1992859
TI  - Sudden appearance of coronary thrombus observed by angiography--a case report.
AB  - A sudden coronary thrombus formation was documented by chance during cardiac
      catheterization in a patient with postinfarction angina. The thrombus was
      successfully treated with intravenous urokinase and heparin infusions, and
      thereafter, coronary angioplasty was performed without any complication.

PMID- 1992860
TI  - How long can a coronary reperfusion catheter be placed in acute coronary
      occlusion following failed transluminal coronary angioplasty? A case report.
AB  - A coronary reperfusion catheter (CRC) is designed to preserve antegrade coronary
      flow when abrupt coronary closure occurs during percutaneous transluminal
      coronary angioplasty (PTCA). Insertion of the catheter to an occluded coronary
      artery for a few hours has been reported to be effective for myocardial salvage:
      however, it is unknown how long the catheter can be kept in place without causing
      extension of myocardial ischemia. The authors experienced a case in which the CRC
      was kept in place for twenty-four hours for anticoagulant therapy of an occluded
      coronary artery following failure of PTCA. This case suggests that adequate
      anticoagulant therapy can prolong the period during which a CRC can be kept in
      place if emergency coronary bypass surgery cannot be performed immediately after
      failure of coronary angioplasty.

PMID- 1992861
TI  - Spontaneous cerebral embolism from descending thoracic aortic aneurysm--a case
      report.
AB  - A case in which an aneurysm of the proximal descending thoracic aorta was the
      likely source of retrograde cerebral embolism is described. Atherosclerotic
      disease of the descending thoracic aorta should be considered as an unusual
      source of cerebral emboli.

PMID- 1992862
TI  - Long-term evaluation of indobufen in peripheral vascular disease.
AB  - Indobufen--an inhibitor of platelets aggregation--has been used in 306 patients
      with intermittent claudication due to peripheral vascular disease. Patients were
      treated and followed up for one year. One patient of every 3 treated with
      indobufen was treated with ASA, and a control group of patients receiving no
      treatment was also followed up. The authors studied by means of a treadmill
      exercise test the pain-free walking distance (PFWD), the global walking distance
      (GWD), and the recovery time after exercise. The treatment period was completed
      by 290 patients: 204 claudicants, 51 claudicants with diabetes, and 35 with a
      short PFWD and GWD (greater than 150 m). Indobufen was more effective than ASA in
      improving the PFWD and GWD in all groups. There were also fewer side effects with
      indobufen, and cardiac morbidity and mortality was also reduced. In conclusion
      indobufen showed its activity and safety in chronic treatment of patients with
      peripheral disease, and we suggest that it may be used for long periods without
      side effects.

PMID- 1992863
TI  - Total occlusion of the left main coronary artery in a young woman with survival:
      a case report.
AB  - The total occlusion of the left main coronary artery (LMCA) is rare, and the
      survival depends on the existence of collateral circulation. The author presents
      a case of total occlusion of the left main coronary artery with survival in a
      young woman because he thinks this is a very rare case, owing to the sex and age
      of the patient.

PMID- 1992864
TI  - Axillary subclavian vein thrombosis. Changing patterns of etiology, diagnostic,
      and therapeutic modalities.
AB  - Fifty-two patients with axillary-subclavian vein thrombosis were treated in the
      last 10 years and were available for follow-up for at least 1 year. Eighteen of
      these were treated in the first 5 years, Group A, and 34 in the last 5 years,
      Group B. The causes in both Group A and Group B included respectively: effort or
      spontaneous 28 per cent and 29 per cent, catheter insertion related 17 per cent
      and 47 per cent, and malignancy or systemic disease 55 per cent and 24 per cent.
      None of the patients in Group A had noninvasive vascular testing (NIT). However,
      27 patients in Group B had IPG/duplex imaging (NIT). All 18 cases in Group A and
      27 cases in Group B were treated conventionally (anticoagulants). Seventy-three
      per cent of these had residual pain on exertion (venous claudication) and/or
      swelling. Fourteen of these cases had posttreatment NIT/venography. Four of these
      showed total resolution of the thrombus and all were symptom free. Ten had no
      resolution, and nine were symptomatic. Seven cases in Group B were treated with
      thrombolytic therapy. Five of these had total resolution of thrombus and were
      symptom free (71%). Two had no resolution with residual symptoms (29%)
      (statistically significant). In conclusion (1) More patients with axillary
      subclavian vein thrombosis seen recently are catheter insertion related; 2)
      Diagnosis should be initiated with duplex imaging; and (3) Thrombolytic therapy
      significantly decreased residual symptoms and yielded better resolution than
      anticoagulants.

PMID- 1992865
TI  - Splenectomy for the massively enlarged spleen.
AB  - The experience at the National Cancer Institute from 1955 to 1988 with 46 cases
      of splenectomy for massive splenomegaly (greater than or equal to 1,500 grams)
      was reviewed to assess the indications, pathology, operative, and postoperative
      course for this procedure. The median age was 51 years. Thirty-one splenectomies
      (67.4%) were performed for malignancy (chronic lymphocytic leukemia, 11; chronic
      myelogenous leukemia, 10; lymphoma, 9; hairy cell leukemia, 1), 11 for myeloid
      metaplasia, and four for other nonmalignant conditions. Indications for
      splenectomy included hypersplenism (32 patients), symptoms (6), diagnosis (3),
      and splenic rupture (3). A midline incision (30 patients) was most commonly used.
      Median operative time was 2 hours, 50 minutes. Median operative blood loss was
      1,300 ml (range, 100 ml-60 units). The splenic artery was ligated initially in 16
      patients (34.8%) but did not correlate with blood loss or operating time. The
      median splenic weight was 2,030 grams (range, 1500-5320 gm). The postoperative
      complication rate was 39.1 per cent (21 complications in 18 patients). This
      included infection in 10 patients, bleeding in six patients. Six patients
      required reoperation (bleeding, 4; abscess, 1; small bowel obstruction, 1
      patient). The 30-day operative mortality was 19.6 per cent (9 patients).
      Excluding operative deaths, 35 patients were available for follow-up evaluation.
      Twenty-nine patients had improvement in parameters for which splenectomy was
      indicated. Six patients had no change in their course after splenectomy. These
      findings indicate that many patients with massive splenomegaly benefit from
      splenectomy, however, the procedure is associated with a high risk for
      postoperative morbidity and mortality.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1992866
TI  - Pancreas transplantation. A new program.
AB  - Sixteen pancreatico-duodenal transplants were performed on 15 insulin-dependent
      diabetics, aged 25-46, during a 20-month period beginning May 1, 1988. Fourteen
      patients received a combined cadaveric pancreas/renal transplant with bladder
      drainage. One patient received a second pancreas transplant 24 hours after the
      first pancreas graft failed due to portal vein thrombosis. One patient received a
      pancreas graft 3 years after kidney transplantation. Complications included five
      cases of hematuria, two bladder leaks, two wound infections, one cytomegalovirus
      pneumonia, three cases of graft pancreatitis, one pseudocyst, one urine reflux
      pancreatitis requiring conversion to pancreatico-enterostomy, and two late
      deaths. Average time to discharge was 17 days following transplant, with 2.9 re
      hospitalizations per patient and an average of 38 in-hospital days during the
      first 6-12 months. Seventeen rejection episodes occurred in 12 patients,
      diagnosed by declining urine amylase and pH and/or finding of rejection on kidney
      biopsy. Patient and kidney graft survival is 87 per cent. Pancreas graft survival
      is 81 per cent (1-20 months follow-up). All patients are insulin-independent and
      normoglycemic. Mean glycosylated hemoglobin concentration is 4.0 +/- 0.9 post
      transplant vs. 7.5 +/- 0.6 pretransplant. Mean serum creatinine is 1.4 +/- 0.7
      mg/dl. A new program of pancreas transplantation can be successful in carefully
      selected diabetic patients, with special attention to avoidance of preservation
      injury to the pancreas during multiorgan donor procurement. Combined
      pancreatic/renal transplantation is believed to be the therapeutic treatment of
      choice in Type I diabetic patients who have impaired renal function and have no
      significant cardiovascular disease.

PMID- 1992867
TI  - Ischemic colitis. An ever-changing spectrum?
AB  - Ischemic colitis, or more properly colonic ischemia, became a clear clinical
      entity in the past 25 years. Yet, early diagnosis of this disease with its
      various presentations remains a difficult task. A 10-year review at our hospital
      identified 38 patients with colonic ischemia for comparison with the authors'
      previous experience and with data from the literature. Several important factors
      emerge: (1) Twice as many cases occurred after operations (34% in this series vs.
      16% in the past), probably because fewer and fewer spontaneous cases were
      hospitalized. (2) Sixteen patients required operative intervention for colonic
      ischemia with a mortality of 62 per cent, while those treated nonoperatively had
      a mortality of 14 per cent. Seven of eight postoperative patients who required a
      second operative procedure for their colonic ischemia died. A high clinical
      suspicion is necessary in the postoperative patient, as colonic ischemia appears
      to be more severe among these patients. Moreover, the high incidence of
      associated cardiovascular disease indicates that early diagnosis, as well as
      monitoring of the "at-risk" patient, is needed for improvement in survival to
      occur. New monitoring methods, such as tonometry, may help accomplish this goal.

PMID- 1992868
TI  - Hemodynamic effects of pressure support ventilation in cardiac surgery patients.
AB  - Hemodynamic consequences of pressure support ventilation (PSV) were compared with
      intermittent mandatory ventilation (IMV) in 20 patients following aortocoronary
      bypass. On the morning following surgery, all patients were weaned by IMV to a
      rate of eight breaths per minute, tidal volume of 12 ml/kg and inspired oxygen
      concentration of 40 per cent. With patients awake and able to breath
      spontaneously, PSV was begun at 20 cm of water. In patients with static lung
      compliance, less than 0.06 l/cm H2O, 30 cm H2O of PSV was used. Subsequently, all
      patients were weaned to PSV 10 cm of water, continuous positive airway pressure
      (CPAP) at 5 cm water and extubated. Hemodynamic data including oxygen transport
      were obtained at each level of PSV and at IMV prior to weaning. Analysis using
      ANOVA showed comparable hemodynamic and oxygen transport parameters for PSV of 30
      cm H2O in comparison with IMV. PSV at levels of 20 and 10 cm H2O produced
      statistically significant increases in heart rate, mean arterial pressure,
      central venous pressure, and pulmonary capillary wedge pressure. Cardiac output
      was stable, and these increases were not clinically significant. In awake
      patients following cardiac surgery, PSV up to 30 cm H2O can be safely applied
      without hemodynamic embarrassment in patients with good left ventricular ejection
      fractions.

PMID- 1992869
TI  - Diagnostic peritoneal lavage. Limited indications due to evolving concepts in
      trauma care.
AB  - This study was undertaken to determine the appropriateness of celiotomy in 100
      consecutive patients who underwent celiotomy solely because of positive
      diagnostic peritoneal lavage (DPL) following blunt (B) or stab (S) abdominal
      trauma. A total of 32 (32%) patients had positive DPL by laboratory criteria:
      blunt trauma: greater than 100K RBC/mm3, greater than 500 WBC/mm3; stab trauma:
      greater than 50K RBC/mm3, greater than 250 WBC/mm3. DPL in 68 patients was
      positive by gross inspection; 18 of these 68 patients' DPL laboratory results
      returned after surgery and did not satisfy the laboratory definition of positive
      DPL. In all 61 per cent underwent therapeutic celiotomy (TC) and 39 per cent
      underwent nontherapeutic celiotomy (NTC). Grade I and II spleen and/or liver
      injuries led to 79 per cent of NTCs. Positive DPL, determined by gross inspection
      or by laboratory testing, has a very poor accuracy rate when evaluated in light
      of evolving beliefs that promote nonoperative therapy for grade I and II liver
      and spleen injuries. When positive DPL is the sole indication for celiotomy in
      patients with blunt or stab abdominal trauma, an unacceptably large number of
      NTCs will be performed. DPL should have a limited role in the evaluation of
      patients with abdominal trauma.

PMID- 1992870
TI  - Relevance of methods of skin incision technique on development of wound
      infection.

PMID- 1992871
TI  - Bacterial phagocytosis in obstructive jaundice. A microbiologic and electron
      microscopic analysis.
AB  - Reticuloendothelial system dysfunction has been suggested as an explanation for
      the increased susceptibility to infection in patients with obstructive jaundice.
      In the present study, the response of cholestatic rats to a bacterial challenge
      was investigated and the uptake of bacteria by their Kupffer cells was examined
      with the electron microscope. Rats underwent bile duct ligation (BDL, n = 8) of
      sham celiotomy (SC, n = 8) and were allowed to recover for 10 days. They were
      then injected with 10(9) Staphylococcus aureus IV and killed at intervals of 15,
      30, 60, and 180 minutes after injection. Two from each group were killed at each
      interval. Quantitative blood cultures were performed, and specimens of liver and
      lung were obtained for quantitative bacterial culture and processed for electron
      microscopy. Bacteria were rapidly cleared from the bloodstream of SC animals but
      persisted in BDL rats. Electron microscopy consistently demonstrated bacteria
      within Kupffer cell phagocytic vesicles of both SC and BDL animals at each
      interval selected. There was no morphologic difference in these vesicles between
      the two groups. Bacteremia persists in BDL rats subjected to a bacterial
      challenge despite rapid uptake of bacteria in apparently normal phagocytic
      vesicles. This study suggests a defect in intracellular killing of bacteria, an
      impairment of delivery of bacteria to RE cells, or a combination of these
      factors.

PMID- 1992872
TI  - Intraoperative pancreatic fine needle aspiration biopsy. Results in 166 patients.
AB  - Intraoperative fine needle aspiration biopsy (NAB) of undiagnosed pancreatic
      masses was studied in 166 patients over a 17-year period. The cytologic diagnoses
      were correlated with histologic specimens, autopsy results, or clinical follow-up
      (benign disease was documented if the patient was alive without malignancy at
      least 2 years after laparotomy). Aspirates were interpreted as benign,
      suspicious, malignant, or unsatisfactory. Malignant disease was the final
      diagnosis in 109 patients; the cytology was concordant in 101 and was interpreted
      as suspicious in four. Four patients with benign cytology later proved to have
      malignant disease--a false-negative rate of 2.5 per cent. A total of 57 patients
      had benign disease; 51 of these had benign cytology. The remaining patients had
      "unsatisfactory" cytology reports. A 93 per cent sensitivity, 100 per cent
      specificity, and 0 per cent complication rate are reported. There were no false
      positive cytology reports. Complications are rare and represent case reports,
      thus, additional sampling is at minimal risk. Intraoperative pancreatic NAB is a
      safe, easy, more accurate biopsy technique than historical wedge or core needle
      biopsies. It is the biopsy method of choice for pancreatic masses found at
      laparotomy.

PMID- 1992873
TI  - Evaluation of three techniques for documenting Staphylococcus epidermidis
      vascular prosthetic graft infections.
AB  - Staphylococcus epidermidis (S. epidermidis) vascular prosthetic graft infections
      are notoriously hard to detect. Three different techniques of determining whether
      vascular prosthetic grafts were infected using a dog model were evaluated. Aortic
      angiograms were compared with nuclear magnetic resonance (NMR) imaging and
      systemic norepinephrine (NE) kinetics to determine if either newer technique
      would be more reliable than standard angiograms. Twelve dogs were randomized to
      control (n = 6) or infected groups (n = 6). All dogs had a 5 cm section of their
      infrarenal aorta replaced with knitted Dacron vascular prosthetic graft. The
      grafts in the infected group were contaminated by soaking them in a broth
      containing S. epidermidis. NE production and clearance rates were calculated for
      all animals after an infusion of 3H-NE using the steady-state radionuclide tracer
      methodology. One week following graft insertion, dogs were reanesthetized, and
      the 3H-NE infusion and measurements were repeated. Standard angiograms and NMR
      imaging were also performed. Once all tests were performed, the prosthetic grafts
      were removed for cultures. Comparisons between the initial and final
      norepinephrine measurements for each group were made using the nonparametric
      Wilcoxon two-sample test, while comparisons between the groups were made by chi
      square or the Student's t test. Angiogram results were similar for control and
      infected animals. Angiograms missed disruption of the proximal anastomosis found
      in three of the six infected dogs at graft removal. None of the six control
      animals, while five of the six infected animals, had localized areas of high
      signal intensity on NMR imaging (P less than 0.01) suggesting abscess
      formation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1992874
TI  - Effect of oxygen-free radical scavengers on survival in sepsis.
AB  - Sepsis remains a leading cause of death in the surgical intensive care unit
      (SICU) patient following major surgery or trauma. Recent work has demonstrated
      that oxygen-free radicals (OFR) generated during sepsis contribute to the
      pathogenesis of this syndrome. The purpose of this study was to evaluate the
      effect of various new free radical scavengers on survival in sepsis. A total of
      85 male Sprague-Dawley rats were placed into one of the following treatment
      groups. CONTROL: cecal ligation and puncture (CLP); PRE-AT: pretreatment with
      alpha-tocopherol (AT) 10 mg/100 gm SC x 3 days, and 5 mg/100 gm IV prior to CLP;
      AT: 20 mg/100 gm at time of CLP and 4 hours following CLP; U74006F: (21
      aminosteroid which inhibits lipid peroxidation) 3 mg/kg IV at the time of and 4
      hours following CLP; U78517F: (alpha-tocopherol analogue) 3 mg/kg at the time of
      and 4 hours following CLP. Survival was determined at various time points up to
      72 hours. Pretreatment with AT resulted in improved survival, whereas the novel
      OFR scavengers U78517F and U74006F significantly improved survival and were
      efficacious without pretreatment. It was concluded that OFR scavengers can
      improve survival in sepsis.

PMID- 1992875
TI  - Multilevel occlusive vascular disease presenting with gangrene.
AB  - The medical records of all patients subjected to lower extremity amputations
      during a 3-year period were reviewed. It was shown that advanced age and the
      presence of multiple medical problems do not predispose to higher levels of limb
      loss. Although diabetic patients more frequently undergo amputation because of
      sepsis than their nondiabetic counterparts, the diabetic state was not found to
      be associated with a greater likelihood of above knee (AK) procedures. Prior
      arterial surgery was not shown to make AK amputation more likely, but it was
      disconcerting to note that limb salvage was not achieved in many individuals
      despite patent proximal inflow revascularization procedures. This initial study
      showed that several presumed risk factors were not predictors of amputation
      level. Those patients requiring AK amputations had a greater frequency of
      combined segment (aortoiliac and femoropopliteal) occlusive disease than those
      who had successful amputations at more distal levels. A follow-up study of 41
      consecutive patients presenting with tissue loss due to combined segment
      occlusive disease was performed. Eighteen (Group I) underwent inflow procedures
      only, while 23 (Group II) also underwent distal revascularization. The groups
      were similar with respect to age, risk factors, extent of tissue loss and sepsis.
      At 1 year 10 (56%) Group I and only 3 (13%) Group II patients required major
      amputation (P = 0.01). Distal bypass, in addition to an inflow procedure, is
      recommended for those who present with tissue loss due to multilevel arterial
      occlusion.

PMID- 1992876
TI  - Lack of benefit of methotrexate in severe, steroid-dependent asthma. A double
      blind, placebo-controlled study.
AB  - OBJECTIVE: To determine the effect of low-dose methotrexate in asthmatic patients
      on steroid use, asthma symptom scores, pulmonary function, airway reactivity,
      blood cellular components, and immunoglobulin E levels. DESIGN: A randomized,
      double-blind, parallel, placebo-controlled, 13-week clinical trial with follow-up
      of patients in an open trial of methotrexate at the conclusion of the double
      blind study. SETTING: An asthma care outpatient clinic. PATIENTS: From February
      1988 to March 1990, 19 patients with severe, steroid-dependent asthma were
      enrolled in the study. Two of these patients were excluded from analysis.
      INTERVENTIONS: Patients were administered methotrexate or placebo
      intramuscularly, to assure complete absorption, once weekly during the 13-week
      study. RESULTS: Patients on methotrexate and placebo both significantly decreased
      their steroid dose by 39.6% (95% CI, 25.1% to 54.1%, P = 0.001) and 40.2% (CI,
      17.9% to 67.4%, P = 0.003), respectively. Pulmonary function did not differ
      significantly between the methotrexate and placebo groups. In addition, airway
      reactivity and symptom scores were unchanged on methotrexate or placebo. No
      significant toxicities were seen during the course of the 13-week blinded study,
      but one patient on methotrexate and prednisone in the follow-up period developed
      Pneumocystis carinii pneumonia and died. Despite continuing methotrexate for up
      to 1 year, and increasing methotrexate to 30 mg weekly, no significant benefit of
      methotrexate on asthma control could be shown. CONCLUSION: Our study does not
      support the use of methotrexate in the treatment of severe asthma.

PMID- 1992877
TI  - Erythrocyte sedimentation rate predicts early relapse and survival in early-stage
      Hodgkin disease. The EORTC Lymphoma Cooperative Group.
AB  - OBJECTIVE: To assess the value of an elevated (greater than 30 mm/h) Westergren
      erythrocyte sedimentation rate (ESR) for predicting early relapse and survival
      after therapy in patients with clinical stage I or II Hodgkin disease.
      INTERVENTIONS: We studied 772 patients with early-stage Hodgkin disease who had
      participated in two separate multicenter clinical trials. Both trials used modern
      field radiotherapy and, in some patients, multi-agent chemotherapy. MAIN RESULTS:
      The ESR patterns were based on pretherapy and post-therapy assessments: pattern
      1, always normal (n = 261); pattern 2, elevated before therapy but normal
      immediately after therapy (n = 121); pattern 3, elevated before therapy but
      normal within 3 months after therapy (n = 89); pattern 4, always elevated (n =
      48); pattern 5, normal before therapy but oscillating between normal and elevated
      after therapy (n = 150); pattern 6, elevated before therapy but oscillating
      between normal and elevated after therapy (n = 130). By multivariate analysis,
      independent of whether or not patients received chemotherapy in the initial
      therapy protocol, ESR patterns 4, 5, and 6 were shown to be the best predictors
      for early relapse and survival when patients were stratified according to the
      type of chemotherapy received and the number of involved nodal areas. Patients
      with ESR pattern 4 had a relative risk for death seven times that of patients
      with patterns 1, 2, or 3. Early relapse was the second most important factor
      predicting death, irrespective of ESR; patients with early relapse and ESR
      patterns 1, 2, or 3 had a relative risk for death of 4.5, and those with early
      relapse and ESR patterns 4, 5, or 6 had a relative risk for death of 15. Whether
      or not chemotherapy was given initially did not change the relative risk, which
      shows that ESR, not initial therapy, was the predictor for early relapse and
      death due to Hodgkin disease. CONCLUSION: An unexplained elevated ESR after
      therapy, especially after modern radiotherapy, independent of other factors,
      strongly suggest the presence of aggressive and resistant Hodgkin disease. An
      elevated ESR is predictive of early relapse and poor prognosis; its presence
      justifies early aggressive therapy.

PMID- 1992878
TI  - AIDS enteropathy: occult enteric infections and duodenal mucosal alterations in
      chronic diarrhea.
AB  - OBJECTIVE: To investigate occult enteric infections and morphologic changes in
      the small intestine in patients with advanced human immunodeficiency virus (HIV)
      infection and chronic diarrhea of undefined cause. DESIGN: Case-control study.
      SETTING: Referral-based clinic and hospital in tertiary care center. PATIENTS:
      Twenty-two patients with advanced HIV infection (19 with the acquired
      immunodeficiency syndrome [AIDS], 3 with AIDS-related complex) with chronic
      diarrhea, selected because of previously negative stool evaluations for bacterial
      or parasitic pathogens, were compared with 13 patients with advanced HIV
      infection (9 with AIDS, 4 with AIDS-related complex) without diarrhea by analysis
      of endoscopic biopsies using light and electron microscopy, viral culture, and
      morphometric studies. Both groups were convenience samples and had at least 7
      months follow-up. MEASUREMENTS AND MAIN RESULTS: Eleven of twenty-two patients
      with HIV infection and chronic diarrhea but only 1 of 13 patients without
      diarrhea showed occult enteric pathogens (that is, undetected by routine studies)
      after extensive evaluation of duodenal and colorectal biopsies. Mycobacterium
      avium-intracellulare and microsporidia were the most common occult agents in
      study patients with diarrhea (5 each). Patients with diarrhea and occult enteric
      infections had greater weight loss (mean, 14.3 kg compared with 6.2 kg; P less
      than 0.05) and shorter survival (1 of 11 compared with 8 of 11 still alive; P
      less than 0.004) than those with diarrhea but no identified pathogens (defined as
      "AIDS enteropathy"). Duodenal morphometry showed decreased villus-to-crypt ratios
      because of villus atrophy and crypt elongation in HIV-infected patients both with
      and without diarrhea compared with normal controls (P less than 0.001 for each).
      All three groups showed comparable frequencies of epithelial mitoses.
      CONCLUSIONS: Further endoscopic biopsy evaluation of patients with AIDS who had
      unexplained chronic diarrhea showed an occult infectious cause in half of the
      cases. However, altered villus and crypt architecture in advanced HIV infection
      was independent of the presence of diarrhea or enteric infection and therefore
      did not correlate with AIDS enteropathy. Subnormal epithelial proliferation in
      response to injury could be a factor, but the underlying cause of the
      architectural changes remains obscure. We suggest that T-cell dysfunction may
      play a role.

PMID- 1992879
TI  - Increased sympathetic outflow in cirrhosis and ascites: direct evidence from
      intraneural recordings.
AB  - OBJECTIVE: To determine if central sympathetic outflow is increased in patients
      with cirrhosis and ascites. PATIENTS: Eleven patients with cirrhosis and ascites,
      8 patients with cirrhosis but without ascites, and 7 age-matched and 8 young
      healthy volunteers. METHODS: With subjects supine, direct microneurographic
      recordings of efferent post-ganglionic muscle sympathetic nerve activity were
      obtained from the peroneal nerve, and sympathetic burst frequency was compared
      with subjects' blood pressure, heart rate, sodium excretion, catecholamines, and
      plasma renin activity. All patients with cirrhosis were studied at least 5 days
      after withdrawal from all medications and after 7 days of a 20 mmol/d sodium, 1-L
      fluid-restricted diet. Age-matched volunteers were studied after 7 days of 20
      mmol/d sodium intake and young healthy volunteers after 7 days of 150 mmol/d
      sodium intake. RESULTS: Sympathetic nerve activity in ascitic patients (65 +/- 15
      bursts/min; mean +/- SD) was markedly increased, whether compared with patients
      with cirrhosis but without ascites (34 +/- 16 bursts/min; P less than 0.001), age
      matched healthy volunteers on similar sodium intake (27 +/- 22 bursts/min; P less
      than 0.001), or young healthy subjects (21 +/- 10 bursts/min; P less than 0.001).
      The frequency of muscle sympathetic nerve discharge was directly related to
      plasma norepinephrine and epinephrine concentrations, plasma renin activity, and
      heart rate, all of which were increased in those patients with cirrhosis and
      ascites, and inversely related to 24-hour urinary sodium excretion, the
      fractional excretion of sodium, and subjects' pulse pressures. Sympathetic nerve
      activity fell from 78 to 6 bursts/min in one patient after liver transplantation.
      CONCLUSIONS: This study provides the first direct evidence that elevated plasma
      norepinephrine concentrations in patients with cirrhosis and ascites are due to
      increased central sympathetic outflow. Sympathetic nerve activity is not
      increased in patients with cirrhosis but without ascites. Because there were
      direct positive correlations of sympathetic nerve activity with plasma
      norepinephrine concentrations, plasma epinephrine concentrations, plasma renin
      activity, and heart rate, the increase in central sympathetic outflow in patients
      with cirrhosis and ascites appears generalized and not restricted to muscle
      nerves. The anti-natriuretic effects of parallel increases in renal and muscle
      sympathetic nerve activity could account for the inverse correlation between
      muscle sympathetic nerve activity and sodium excretion.

PMID- 1992880
TI  - Do life events or depression exacerbate inflammatory bowel disease? A prospective
      study.
AB  - OBJECTIVE: To determine whether depressed mood or life events are associated with
      an exacerbation of inflammatory bowel disease. DESIGN: A prospective study of a
      consecutive sample of patients with relapsing inflammatory bowel disease,
      followed by monthly questionnaires and periodic office visits. SETTING: A
      referral-based gastroenterology clinic at a medical school. PATIENTS: A
      consecutive sample of 32 patients with inflammatory bowel disease who had had at
      least one relapse in a 2-year period after entry into the study. MEASUREMENTS AND
      MAIN RESULTS: The Social Readjustment Rating Scale (measuring life events), the
      Beck Depression Inventory (a visual analog scale for depressed mood) and an
      inventory of intestinal symptoms were completed monthly by each subject with a
      78% rate of compliance. A mean of 2.2 exacerbations was seen per subject during
      the study period. Life events were not temporally associated with changes in
      intestinal symptoms. Significant associations were found between intestinal
      symptoms and the two mood scales (P less than 0.05 for each), but no
      directionality in symptom occurrence could be detected in a time-lagged analysis.
      The results were similar when the months preceding exacerbations of inflammatory
      bowel disease were analyzed separately. CONCLUSIONS: Although these findings
      suggest that mood changed concurrently with exacerbation of inflammatory bowel
      disease, no evidence indicated that stressful life events or depressed mood
      precipitated exacerbations in this study group.

PMID- 1992881
TI  - The acute lupus hemophagocytic syndrome.
AB  - OBJECTIVE: To characterize an unusual mode of presentation of systemic lupus
      erythematosus: acute and severe pancytopenia related to reactive
      hemophagocytosis. DESIGN: Retrospective case series. SETTING: Two general
      community hospitals in Hong Kong. PATIENTS: Six patients presenting with a
      reactive hemophagocytic syndrome, identified over a 3.5 year period, diagnosed
      with systemic lupus erythematosus according to the criteria of the American
      Rheumatism Association. RESULTS: In addition to severe pancytopenia and marrow
      hemophagocytosis, other characteristic features were fever, hypocomplementemia,
      high antinuclear antibody titer, and cutaneous and visceral vasculitis. There was
      no evidence of an underlying infection. The pancytopenia responded dramatically
      to treatment with steroids. CONCLUSION: Recognition of the acute lupus
      hemophagocytic syndrome and distinction from an infection-associated
      hemophagocytic syndrome is important because it responds well to steroid therapy.
      The evaluation of patients presenting with a hemophagocytic syndrome should
      include serologic tests for systemic lupus erythematosus.

PMID- 1992882
TI  - Atheromatosis of the aortic arch as an occult source of multiple systemic emboli.

PMID- 1992883
TI  - Assessment of clinical skills of residents utilizing standardized patients. A
      follow-up study and recommendations for application.
AB  - OBJECTIVE: To determine the reliability and validity of "standardized patients"
      to assess clinical performance of internal medicine residents. DESIGN: Each
      resident spent 2 half-days interacting with 19 standardized patients
      (nonphysicians taught to portray patients in a reproducible fashion). Each
      resident was asked to obtain focused histories, perform relevant physical
      examinations, and provide patient education or counseling. At the end of each 10-
      to 15-minute encounter, the resident was asked to identify positive findings on
      physical examination and to prioritize a differential diagnosis. Other, more
      traditional indicators of clinical skills were also obtained. PARTICIPANTS: Three
      hundred ten residents from nineteen internal medicine training programs in the
      New England region of the United States. RESULTS: Reproducible estimates of data
      gathering and interviewing skills were achieved with 1 day of testing. Validity
      analyses were difficult to interpret because of the lack of an external "gold
      standard." However, faculty judgments of performance from reviewing videotapes
      corresponded with standardized-patient-based scores. Differences in group
      performance were also demonstrated across years of training and between U.S. or
      Canadian and foreign medical graduates. CONCLUSIONS: Systematic and effective
      procedures for developing standardized-patient-based test materials and for
      training standardized patients have been developed. This technique is best used
      for measuring data gathering and interviewing skills. Correlations with commonly
      used evaluation methods were generally low; this may be because standardized
      patients measure different skills. Local use of this technique by residency
      programs and the development of regional consortia sharing resources, costs, and
      expertise are advocated.

PMID- 1992884
TI  - Recombinant human erythropoietin and renal anemia: molecular biology, clinical
      efficacy, and nervous system effects.
AB  - Anemia (hematocrit less than 25%) predictably accompanies chronic renal failure
      and is present in over 90% of patients on chronic dialysis. Relative
      erythropoietin deficiency is the proximate cause. Recombinant human
      erythropoietin recently became available for research and clinical use.
      Erythropoietin production is regulated by a single copy gene located on
      chromosome 7; its expression has been shown in the kidney, liver, and
      macrophages. It is glycosylated protein of 166 amino acids with a molecular
      weight of 34,000 D. When given to patients with the anemia of renal failure,
      erythropoietin causes a dose-dependent rise in hematocrit to the normal range
      within 8 to 14 weeks. Complications of this response are minimal except for a
      significant incidence of hypertension. When the anemia is corrected, the
      patient's quality of life, cognitive function, and brain electrophysiology
      improve dramatically. Recombinant human erythropoietin represents a major
      breakthrough in the treatment of patients with chronic renal failure. Current
      reimbursement constraints limit its full application.

PMID- 1992885
TI  - Emerging resistance to fluoroquinolones in staphylococci: an alert.

PMID- 1992886
TI  - University medical center participation in residency training programs for
      graduates of foreign medical schools.

PMID- 1992887
TI  - Clinical prediction of pneumonia.

PMID- 1992888
TI  - Gastrointestinal bleeding in runners.

PMID- 1992889
TI  - Anti-neutrophil cytoplasmic autoantibody-associated glomerulonephritis.

PMID- 1992890
TI  - Acetaminophen, isoniazid, and hepatic toxicity.

PMID- 1992891
TI  - Drug abuse and stroke.

PMID- 1992892
TI  - Colorectal cancer: heredity and environment.

PMID- 1992893
TI  - Unnecessary preoperative tests: the hospital's role.

PMID- 1992894
TI  - Time-limited certification.

PMID- 1992895
TI  - Treatment of intractable aspiration using a laryngeal stent or obturator.
AB  - Twenty-five patients were treated with a laryngeal stent for potentially
      reversible chronic aspiration of life-threatening magnitude. The causes of the
      intractable aspiration were diverse and included chronic neurologic disease,
      extensive head and neck surgery, and severe gastroesophageal reflux. The
      advantages of this technique are noted in comparison to those of more invasive
      procedures. Disadvantages of the laryngeal stent and complications encountered
      are also covered. The long-term results show that all but one patient had a
      significant improvement in their chronic aspiration with the stent in place.
      However, only eight patients achieved adequate oral deglutition without
      aspiration following stent removal.

PMID- 1992896
TI  - Transtracheal delivery of oxygen: efficacy and safety for long-term continuous
      therapy.
AB  - Transtracheal (TT) oxygen delivery involves administration of oxygen
      percutaneously through a catheter inserted in the suprasternal trachea.
      Transtracheal oxygen delivery has been proposed as a means of overcoming the high
      visibility, inconvenience, and discomfort associated with nasal cannula use. This
      report describes our experience using TT delivery in 40 patients with chronic
      obstructive pulmonary disease (n = 32) and other types of lung disease (n = 8).
      Overall acceptance of TT catheter use was high and only 5 subjects elected to
      discontinue use. We believe the TT route is a relatively safe approach for oxygen
      administration and a promising method of improving patient compliance. It also
      offers the potential of more adequately oxygenating patients with refractory
      hypoxemia.

PMID- 1992897
TI  - Surgical applications of ultrathin flexible bronchoscopes in infants.
AB  - Ultrathin flexible bronchoscopes with controlled distal angulation allow the
      conventional diagnostic examination of the lower airways of even the smallest
      infants. These instruments may be passed through small endotracheal or
      tracheostomy tubes while ventilation is maintained. It is thus possible, under
      direct visualization, to control the manipulation of surgical instruments where
      they could not otherwise be seen, or to study airway dynamics and anatomy
      intraoperatively without extubating the patient.

PMID- 1992898
TI  - Stapes surgery in osteogenesis imperfecta: analysis of postoperative hearing
      loss.
AB  - The disappointing results in 12 of 58 stapedectomies, including 4 revision
      operations, performed on osteogenesis imperfecta patients were analyzed and
      compared with reports in the literature. It is concluded that the results
      described as disappointing were not always the product of the stapes operation. A
      progressive sensorineural hearing loss arising independently of the operation as
      a result of progression in the disease process of osteogenesis imperfecta appears
      to have a severe influence on the final hearing threshold.

PMID- 1992900
TI  - Skull base malignancy following long-term sinus mucocele and osteomyelitis.
AB  - A case of skull base malignancy following long-term sinus mucocele is presented.
      While the similarity in clinical signs between sinus mucocele and malignancy has
      recently been emphasized in the literature, no previous case of skull base
      malignancy following frontoethmoid mucocele has been reported. The literature is
      reviewed and the association between inflammatory conditions and sinus malignancy
      is outlined.

PMID- 1992899
TI  - Surgical complications with the cochlear multiple-channel intracochlear implant:
      experience at Hannover and Melbourne.
AB  - The surgical complications for the first 153 multiple-channel cochlear implant
      operations carried out at the Medizinische Hochschule in Hannover and the first
      100 operations at the University of Melbourne Clinic, The Royal Victorian Eye and
      Ear Hospital, are presented. In the Hannover experience the major complications
      were wound breakdown, wound infection, electrode tie erosion through the external
      auditory canal, electrode slippage, a persistent increase in tinnitus, and facial
      nerve stimulation. The incidence of wound breakdown requiring removal of the
      package was 0.6% in Hannover and 1.0% in Melbourne. The complications for the
      operation at both clinics were at acceptable levels. It was considered that wound
      breakdown requiring implant removal could be kept to a minimum by making a
      generous incision and suturing the flap without tension.

PMID- 1992901
TI  - Surgical voice restoration with the Blom-Singer prosthesis following
      laryngopharyngoesophagectomy and pharyngogastric anastomosis.
AB  - Surgical voice restoration using the Blom-Singer technique is a well-established
      procedure in patients who have undergone simple laryngectomy. Operations for
      hypopharyngeal carcinoma are more extensive and require reconstruction using
      regional skin or myocutaneous flaps, or reanastomosis with colon, jejunum, or
      stomach. We report the use of the Blom-Singer prosthesis in four patients who had
      undergone pharyngogastric repair following laryngopharyngoesophagectomy and who
      had failed to achieve a satisfactory voice. All patients initially developed good
      speech using the prosthesis. Two patients subsequently had their prostheses
      removed: one because of recurrent malignant disease and one because the procedure
      had not significantly altered the quality of the voice. The remaining two
      patients have continued to use the device at 2 and 5 years after insertion with
      good voice production.

PMID- 1992902
TI  - Ultrastructural evidence of a merocrine secretion in the human endolymphatic sac.
AB  - The results of a light and transmission electron microscopic analysis of an
      endolymphatic sac (ES) from a patient suffering from episodic vertigo, tinnitus,
      and hearing loss are presented. A biopsy of the intraosseous portion of the ES
      was obtained during a translabyrinthine approach to section the vestibular nerve
      in the internal acoustic meatus. The material consisted mainly of tubular
      epithelial structures filled with heavily stained material. Pathologically
      dilated and degranulated rough endoplasmic reticuli and disaggregation of
      polyribosomes with accumulation of solitary ribosomes in the cytosol and
      endoplasmic reticulum suggested a disturbed epithelial cell protein synthesis.
      Ultrastructural evidence of an increased merocrine secretion of glycoprotein
      conjugates into the ES was noted. This made it possible to analyze the presumed
      intracellular secretory pathways. An increased number of intraepithelial
      lymphocytes and monocytes was observed. Since the inner ear had been subjected to
      surgical intervention before the vestibular nerve section, no conclusions can be
      drawn as to whether the patient's symptoms were related to the disturbed protein
      metabolism and hypersecretion of glycoprotein conjugates into the ES. The
      findings support earlier experimental results that indicate that the ES has not
      only a resorptive function but also a secretory one.

PMID- 1992903
TI  - Sphenoid sinus metastasis displacing the cavernous sinus.

PMID- 1992904
TI  - Granulomatous sialadenitis.
AB  - Granulomatous inflammation in salivary tissues is most often a response to
      liberated ductal contents, particularly mucin, in various degrees of obstructive
      sialadenopathy. Far less often is a granulomatous sialadenitis the result of
      specific infective granulomas or systemic granuloma-forming diseases. In these
      instances, the salivary parenchymal involvement is usually secondary to disease
      localization in regional lymph nodes.

PMID- 1992905
TI  - Laryngeal dystonia: a series with botulinum toxin therapy.
AB  - Laryngeal dystonia is a syndrome characterized by action-induced, involuntary
      spasms of the laryngeal muscles. Most patients have involvement of the adductor
      laryngeal muscles producing uncontrolled spasms during phonation, and a "strain
      strangle" speech pattern commonly termed "spastic dysphonia." Other patients have
      involvement of the abductor muscles producing "whispering dysphonia." Rare
      patients have paradoxical vocal cord motion during respiration with adductor
      spasms on inspiration. Over the past 5 years we have used botulinum toxin (BOTOX)
      to treat more than 200 patients with laryngeal dystonia. This group includes
      patients with adductor involvement (phonatory dystonia, recurrent laryngeal nerve
      section failure, respiratory dystonia) and those with abductor involvement
      (whispering dystonia). Patients received benefit within 24 to 72 hours, with
      sustained improvement for 2 to 9 months with an average of 4 months. Patients
      improved to an average of 90% of normal function. Clinically significant adverse
      effects included extended breathy dysphonia and mild choking on fluids. BOTOX has
      become our treatment of choice for dystonic conditions of the larynx.

PMID- 1992906
TI  - Management of subglottic stenosis in the adult.
AB  - Twenty-one adult patients were surgically treated for severe subglottic stenosis
      refractory to endoscopic treatment. Patients were treated by anterior or anterior
      and posterior cricoid division with costal cartilage grafting. Seventy-six
      percent of the patients were successfully decannulated. Success of treatment was
      not dependent on cause of the stenosis or age or sex of the patient. There was a
      significantly better outcome (p less than .05) in patients with isolated
      subglottic stenosis versus those with combined glottic and subglottic stenosis.

PMID- 1992907
TI  - Surgical treatment of laryngeal web with mucosa graft.
AB  - Surgical treatment of laryngeal webbing varies with the extent and site of the
      web. An extensive one seems to be best treated by laryngofissure and skin or
      mucosa transplantation. Recent experiences with four cases of thick glottal
      webbing indicated that a mucosa graft was better for the voice result than a skin
      graft. For success in the airway and voice results, the salient points in surgery
      include 1) precise midline thyrotomy, 2) shaping of the vocal cord under
      fiberoptic control, and 3) mucosa grafting with the combined use of a pliable
      stent or fibrin glue for fixation.

PMID- 1992908
TI  - [New development in clinicopathological diagnosis of brain tumors].
AB  - The prediction of prognosis and the design of treatment modalities for patients
      with brain tumors are judged mostly by its histopathology. The morphology of each
      tumor, however, represents a part of its phenotype, and more attention should be
      paid to understand phenotypic expression of individual tumors in relation to
      cytogenetic abnormality at the molecular level, proliferative potential and
      invasiveness. The author reviewed current studies on cytogenetics, growth
      characteristics of various brain tumors, and experimental approaches for
      invasiveness.

PMID- 1992909
TI  - [New developments of neuro-imaging].
AB  - Magnetic resonance imaging has contributed significantly in the recent
      development of neuro-imaging, especially in recent advances of neuroimaging of
      brain tumors. MR imaging has numerous advantages over CT such as excellent
      contrast resolution, arbitrary imaging planes, no bone artifacts and no
      radiation. Further clinical potential of MR imaging includes fast imaging with
      use of gradient echo technique, 3 dimensional imaging by 3 DFT and MR
      angiography. These new techniques will contribute significantly to the
      advancements of neuroimaging in the near future.

PMID- 1992910
TI  - [Advances of surgery and radiation therapy of glioblastoma and metastatic tumor].
AB  - On the surgery for malignant gliomas, most cases are beyond the stage for
      desirable removal of tumors, because of the risk of damage to the normal function
      of surrounding brain tissue. The restriction of the surgical treatment has
      inevitably required postoperative radiation therapy. With a protocol aiming at
      removing tumors extensively and delivering high dose radiation to the tumor area,
      we treated 107 patients with cerebral glioblastoma. Wide removal of the tumor
      combined with intraoperative radiation therapy (IORT) was applied to expected
      resectable cases at the first surgery or at the second salvage surgery after
      conventional external radiation therapy. Thirty patients underwent extensive
      removal with IORT and demonstrated a 2-year survival rate of 60%. Fifty six
      patients were treated only by postoperative radiation therapy and a two-year
      survival rate was only 6.8%. The results apparently indicate that areas adjacent
      to the margin of almost complete removal should be irradiated with a sufficient
      dose to sterilize the remaining malignant remnants. As metastatic brain tumors
      without systemic metastasis seldom develop to multiple lesions, surgical removal
      followed by local radiation therapy would be ideal in order to prevent brain
      atrophy and dementia induced by whole brain irradiation. IORT would be also
      useful for its strong local effect to tumors and for shortening the hospital stay
      of patients.

PMID- 1992911
TI  - [Chemotherapy of malignant brain tumors--scientific basis for combination
      chemotherapy].
AB  - In the past decade, many clinical trials have been explored for the search of
      effective chemotherapy against malignant gliomas. However, to date, no
      significant prolongation of the survival in adults malignant gliomas have been
      demonstrated by these approaches. Chemotherapy currently adds little to
      radiotherapy in these patients. In solid tumors responsive to chemotherapy,
      multiple effective agents are combined. The design of a chemotherapy regimen
      using multiple drugs should be planned on the basis of several scientific
      theories concerning with tumor biology. Among them, concepts of the alternating
      noncross resistance chemotherapy (Goldie-Coldman) and dose-intense chemotherapy
      were described in relation to application to the chemotherapy of gliomas.

PMID- 1992912
TI  - [Advances of BRM therapy of malignant brain tumors].
AB  - The cooperative study on the beta-interferon (IFN) therapy for glioblastoma and
      malignant astrocytoma reported the response rate as 14.0%. Continuing study
      resulted the response rate of 24.0% to low grade astrocytoma and 20.0% to
      medulloblastoma. Totally, effectiveness of 19.2% to gliomas was confirmed in 120
      evaluated cases. A randomized study was conducted on combination therapy with
      beta-interferon and chemoradiotherapy. The response rate of 41.2% (21/51) in the
      group treated with IFN, ACNU and Radiation was significantly higher than the rate
      of 19.6% (10/51) in the group treated with ACNU and radiation only. Application
      of IFN to a maintenance therapy is also on going. Adoptive immunotherapy has been
      developed as potential therapeutic method of malignant glioma. Lymphokine
      activated killer cells (LAK) and Tumor infiltrating lymphocytes (TIL) are put to
      clinical use. Clinical application of human monoclonal antibody (MAb) CLN-IgG was
      conducted to recurrent malignant glioma. 131I labeled MAb was administered
      intratumorously and the specific incorporation was confirmed by gamma
      scintigraphy. Concomitant administration of interferon enhanced the efficacy of
      the therapy. This radio-immunotherapy holds future promise as a new therapeutic
      approach to gliomas.

PMID- 1992913
TI  - [Microbiological approach to the treatment of brain tumors].
AB  - Growths factors, defined as polypeptides that stimulate cell proliferation, are
      major growth-regulatory molecules for cells in culture and probably also for
      cells in vivo. Evidence has been derived for autocrine system in which the cell
      produces its own growth factor. Several growth factors as well as their cellular
      receptors have been identified as productions of proto-oncogenes. Furthermore,
      these growth factors have been identified as mitogens in tumors of the central
      nervous system. The roles of growth factors including platelet-derived growth
      factor (PDGF), epidermal growth factor (EGF) and its receptor. Insulin-like
      growth factors (IGFs), transforming growth factors (TGFs) and fibroblast growth
      factor (FGF) on the proliferation of brain tumors, especially glioma were
      reviewed. The activation of cellular proto-oncogenes resulting in the autocrine
      system of growth factors and their receptors offers the opportunity for
      therapeutic interference. Therapeutic efforts will be based on the concepts of
      neutralization of growth factors, antagonizing growth factors at their receptors,
      irreversibly blocking receptors, and interference with oncogene product
      synthesis. Specific antibody for growth factors or receptors will be able to
      inhibit the proliferation. Trapidil, an antagonist for PDGF, can inhibit the
      proliferation of a PDGF-producing glioma cell. We can assume that the further
      analysis of growth regulatory mechanism will allow the design of new therapeutic
      approaches.

PMID- 1992914
TI  - [Therapeutic efficacy of fosfomycin and cisplatin alone or in combination on
      human urogenital cancer by subrenal capsule assay].
AB  - Experimental therapies of human urogenital cancer with fosfomycin and cisplatin
      were performed by subrenal capsule assay. The subrenal capsule assay was applied
      for 10 cell lines, consisted of 4 renal cell carcinomas, 2 renal pelvic
      carcinomas, 2 carcinomas of the urinary bladder, one prostatic carcinoma, and one
      testicular tumor. The efficacy of each drug was evaluated by measuring the tumor
      growth, and compared the mean tumor volume of treated with that of untreated
      groups. The growth inhibition rate in fosfomycin group was 60% and in cisplatin
      group was 80%, whereas that of the combination therapy of both fosfomycin and
      cisplatin was 50%. This indicates that the combination therapy reduced the
      antitumor effect. Further, the histological findings also showed a similar
      pattern in both kidney and tumor tissues between the treated and untreated
      groups.

PMID- 1992915
TI  - [Drug concentration in cancerous large bowel tissue and thymidylate synthase
      inhibition rate after administration of tegafur and UFT].
AB  - Tegafur and UFT are most widely used for the treatment of cancers of the
      gastrointestinal tract. FdUMP, a metabolite of 5-fluorouracil(5-FU), is known to
      have an inhibitory activity of thymidylate synthase (TS). We administered 600
      mg/day of tegafur or UFT to 37 patients with cancer of the large bowel beginning
      1 week prior to surgery and then measured the concentrations of tegafur and 5-FU,
      and TS inhibition rate in the excised tissue. Our results showed that the
      concentrations of 5-FU in tumor were 0.077 +/- 0.026 microgram/g in tegafur group
      and 0.208 +/- 0.143 microgram/g in UFT group, with the UFT showing significantly
      higher levels (p less than 0.05). On the other hand, TS inhibition rates in tumor
      tissue were 45.5 +/- 13.3% in tegafur group and 56.1 +/- 13.0% in UFT group, with
      a significantly higher level existing in the latter group (p less than 0.05).
      Furthermore, the same high 5-FU concentration and TS inhibition rates were
      observed in the lymph nodes affected by metastasis. No difference between the
      tegafur and UFT groups was noted in normal tissue or normal lymph nodes, and
      compared to tegafur, UFT showed an effective action on cancerous large bowel
      tissue.

PMID- 1992916
TI  - [Adsorption and desorption of aclarubicin into and from activated carbon
      particles as drug carrier--an in vitro study].
AB  - A new dosage form (ACR-CH), aclarubicin(ACR) adsorbed on activated carbon
      particles (CH), was studied for adsorption and desorption onto and from CH. The
      adsorption isotherm at 37 degrees C in saline and phosphate buffer (pH 7.4-7.5)
      were shown as M = 175 Co.15 and M = 207 Co.24, respectively (M = ACR amount
      adsorbed on CH, microgram/mg; C = ACR concentration in a free state,
      microgram/ml). In both fluids, CH adsorbed more than 100-1,000 times more amount
      of ACR than ACR in a free state. ACR-CH was lavaged 7 times and the released ACR
      in a free state was measured. The results showed that ACR-CH desorbed constantly
      a small amount of ACR, namely, 1.5-8 percent of initial concentration of ACR in a
      free state in saline, 0.1-10% in phosphate buffer, and 0.5-4.0% in Ringer's
      solution. Under the same conditions, desorption of ACR-CH was measured in dog's
      blood plasma. The first lavage made ACR-CH desorb at 25.7 +/- 0.85 percent of ACR
      initial concentration in a free state, and two times' to 7 times' lavage made 1
      3%. Overall, 43.3 +/- 0.99% of ACR were desorbed from the activated carbon. It
      was concluded that ACR-CH slowly released a constant amount of ACR for a long
      period.

PMID- 1992917
TI  - [In vitro chemosensitivity test with several antitumor agents against eight
      malignant brain tumor cell-lines].
AB  - We performed an in vitro chemosensitivity test with 8 malignant brain tumor cell
      lines, which were established in our Department. It was shown that ACNU was
      moderately tumoricidal against only one cell (ONS-86) line. IFN-beta (interferon
      beta) was more active against 4 cell (ONS-6, -20, -76, and -81) lines. VCR
      (vincristine), MTX (methotrexate), and Ara-C (cytosine arabinoside) and FK 973
      were most effective against all 8 cell lines. There were some difference in the
      drug sensitivities among the tumors with the same pathological diagnosis. Since
      IFN-beta was tumoricidal against to the cells, co-culture of IFN-beta and one of
      other antitumor agents seemed to induce more antitumor effects. With regard to
      the side effects of IFN-beta, the combined therapy with IFN-beta and other drugs
      induced more antitumor effects against malignant brain tumor cells and seemed to
      reduce the side effects.

PMID- 1992918
TI  - [Study on the clinical usefulness of NCC-ST-439 in breast cancer].
AB  - We investigated the usefulness of NCC-ST-439, a new tumor marker in breast
      cancer. The positive rate of NCC-ST-439 in cases of primary breast cancer was
      46.9%. In cases of primary breast cancer, there were no significant differences
      in average and positive rate among each group of patient age, tumor size, number
      of metastatic node, clinical stage and status of hormone receptor (ER, PgR). The
      positive rate of NCC-ST-439 in early breast cancer was as high as that in
      advanced case. NCC-ST-439 had better sensitivity than CEA and CA15-3, and
      decreased in serum level after the curative operation. We concluded that NCC-ST
      439 is useful as a screening marker for the detection of early breast cancer and
      as a post operative monitoring marker for the surveillance of the recurrence.

PMID- 1992919
TI  - [Therapeutic effect of ranimustine(MCNU) on myeloproliferative disorder and
      chronic myelomonocytic leukemia].
AB  - Seventeen patients with myeloproliferative disorders and one patient with chronic
      myelomonocytic leukemia (CMMoL) were treated with ranimustine++ (MCNU), and the
      efficacy was evaluated. MCNU was given intravenously by drip infusion at an usual
      dose of 100 approximately 150 mg with intervals arranged according to the counts
      of peripheral blood cells. A complete remission was achieved in all 10 patients
      with chronic myelogenous leukemia (CML) in chronic phase. In three of patients
      with polycythemia vera (PV) the excellent effects were obtained, and the other 2
      cases showed moderate effect. An excellent effect was obtained in both 2 patients
      with essential thrombocythemia (ET). A patient with CMMoL revealed partial
      remission. The overall efficacy rate was 100%. The cases with CML needed more
      long term and much more dose of the drug in order to get remission compared with
      PV and ET. After remission in both PV and ET, well controlled states were
      maintained for a relatively long period with no additional administration. In
      CMMoL, MCNU combined with 6-mercaptopurine also showed remarkable anti-tumor
      effects. It suggests that MCNU may be one of the useful drugs for the treatment
      of CMMoL. The side effects observed with MCNU were a slight degree of nausea and
      vomiting (28%), however they showed no trouble on carrying out the therapy.

PMID- 1992920
TI  - [Evaluation of pre-operative 5-fluorouracil treatment of the patients with
      gastric cancer--alteration of the inhibition rate of thymidilate synthetase by
      dose difference].
AB  - 5-fluorouracil (5-FU) was orally administered before surgical operation to two
      groups of patients, one treated at 300 mg for 7 days and the other treated at 400
      mg for 5 days, to examine the change of TSIR in gastric patients. Tumor tissue,
      lymph node and normal lesions were collected from removed specimens immediately
      frozen. As a result, there were no differences in FdUMP volumes of various
      tissues between 300 mg and 400 mg groups. TSIR tended to be higher in the order
      of normal tissue, lymph node and tumor lesions. TSIR was significantly higher in
      400 mg group than 300 mg group. We believe that further studies on TSIR will
      provide a useful information as to various studies, including efficacy
      reinforcement by combination therapy, problems in resistance, histological
      efficacy and sensitivity tests.

PMID- 1992921
TI  - [A case of Borrmann type 4 gastric cancer well responded to chemotherapy with
      tegafur].
AB  - A 62-year-old female had unresectable stage 4 gastric cancer with ascites. She
      was treated with suppository administration of tegafur 750 mg/day. Endoscopical
      examination before treatment showed Borrmann 4 gastric cancer. After 3 months'
      treatment, the lesion almost disappeared. The patient survived for 9 months after
      the diagnosis.

PMID- 1992922
TI  - [A remarkable effect of K-18 (IgG-melphalan complex) in a case of RAEB with
      hypoplastic marrow].
AB  - A 63-year-old male with refractory anemia with excess of blasts (RAEB) and
      hypoplastic marrow was treated with K-18 (240 mg/day P.O.). On admission,
      peripheral blood revealed pancytopenia. Bone marrow specimen revealed severe
      hypocellularity with 18.9% of the blast cells. Ten months later, the blast cells
      in the bone marrow decreased to 3.8%, and complete remission (CR) was obtained.
      CR was eight weeks. Duration of response (CR + PR) continued for about eight
      months. K-18 is an antitumor agent with minimal side effects, and seems to be
      effective for RAEB with hypoplastic marrow.

PMID- 1992923
TI  - [Long survival in a case of metastatic brain tumor].
AB  - A 45-year-old man was admitted after resection of a metastatic brain tumor
      (papillary adenomatous adenocarcinoma, well differentiated) for both therapy and
      a search for the primary and any other metastatic lesions. An extensive general
      examination revealed no evidence of malignant lesion except for fibrous change in
      the right lung apex by roentgenography and CT scan. Histological examination of
      the right upper lobe and group II lymph nodes revealed a scar cancer presenting
      the same histology but no evidence of metastasis. The patient, who received CAP
      and FVM alternately, is currently healthy with no recurrence after 4 years.

PMID- 1992924
TI  - [Subclass typing of immunoglobulin G paraproteins by isoelectric focusing
      immunoblot method].

PMID- 1992925
TI  - [Comparison of subrenal capsule and subcutaneous assay using nude mouse on
      pancreatic cancer].

PMID- 1992926
TI  - [The effect of tamoxifen on the growth of the human male breast cancer cell line
      (KBC-2)].

PMID- 1992927
TI  - [Tumor markers. Personal experience--screening of breast cancer by determining
      CEA in nipple discharge].
AB  - Secondary prevention, detection and treatment at an early stage, may be the only
      means of controlling breast cancer. This is rational behind screening for breast
      cancer. We have previously reported that CEA measurement in nipple discharge is a
      useful adjunct in the diagnosis of nonpalpable breast cancer. As an extension, a
      dot-immunobinding assay was developed to screen a large number of patients with
      nipple discharge for nonpalpable breast cancer. This article is a review of the
      current status of CEA assay in nipple discharge for mass screening of breast
      cancer. False positive and negative cases will be also described.

PMID- 1992928
TI  - Electroencephalographic findings during experimental human exposure to m-xylene.
AB  - Aromatic hydrocarbon solvents, used widely in industry, cause central nervous
      system symptoms in exposed workers. Acute effects of m-xylene were studied in
      nine voluntary subjects exposed experimentally to stable or varying
      concentrations of m-xylene at rest or while exercising. Each subject participated
      in four exposure and two control sessions in a single-blind fashion. The time
      weighted average (TWA) m-xylene concentration was always 200 parts per million
      (ppm) (8.2 mumol/l) during the 4-h exposure period, complying to a TWA of 4.1
      mumol/l.8 h, which is equivalent to the hygienic limit allowed in work
      situations. The short-term peak concentrations were 400 ppm or less.
      Electroencephalography was recorded at the beginning of exposure, during
      exposure, and after exposure was stopped. Eighteen 60-s EEG samples for each
      subject on each experimental day were analyzed automatically. Exercise increased
      theta percentage and delta power and percentage; these changes were more
      prominent in the control session without exposure. Exposure increased the
      dominant alpha frequency and alpha percentage during the early phase of exposure
      and also counteracted the effects of exercise. The effects of short-term m-xylene
      exposure on EEG were minor, and no deleterious effects were noted. Perhaps alpha
      activation is indicative of stimulating and excitatory effects induced by m
      xylene exposure, which has been noted heretofore in the absorption phase of
      alcohol intake.

PMID- 1992929
TI  - A two-year study of microbiological indoor air quality in a new apartment.
AB  - Concentrations and types of bacteria and fungi in the air and on surfaces were
      measured in a new, one-bedroom apartment before occupancy and at 3-mo intervals
      thereafter for 2 y. Air samples were collected with a single-stage impactor at
      two locations in the kitchen, living room, bedroom, bathroom, and outdoors. Even
      though damp surfaces supported large populations of bacteria and yeasts, the air
      concentrations in the kitchen and bathroom were similar to those in other rooms.
      No changes in concentrations or types of microbiological contamination were
      observed between the first and second years of occupancy, but elevated outdoor
      humidity, lower air temperature, and winds from the northeast were associated
      with higher bacterial and fungal air concentrations. The median air
      concentrations of bacteria were 98 cfu/m3 (95% confidence interval 26-372 cfu/m3)
      indoors and 101 cfu/m3 (28-364 cfu/m3) outdoors. The median air concentrations of
      fungi were 198 cfu/m3 (58-673 cfu/m3) indoors and 362 cfu/m3 (113-1158 cfu/m3)
      outdoors. This information established useful baseline data against which
      measurements in neighboring complaint residences could be compared.

PMID- 1992930
TI  - Radiological abnormalities among sheet-metal workers in the construction industry
      in the United States and Canada: relationship to asbestos exposure.
AB  - We investigated the possible adverse health effects to sheet-metal workers who
      had past exposure to asbestos. A cross-sectional medical examination of 1,330
      workers was conducted during 1986 and 1987 in seven cities in the United States
      and Canada. A total of 1,016 workers had been employed for at least 35 y in the
      industry, and the mean duration from onset of asbestos exposure was 39.5 y (SD =
      7.41 y). Chest x-ray abnormalities were found in more than half of the group.
      Pleural fibrosis, the most frequently found abnormality, was present in 47.0% of
      the cases and was the only abnormality found in 27.8% of cases; parenchymal
      interstitial fibrosis, found in 33.1% of cases, was the only abnormality found in
      16.2% of cases. Radiologic abnormalities increased as duration of exposure
      increased. A positive smoking history was associated with a higher prevalence of
      radiologically detectable parenchymal abnormalities, a finding confirmed by us
      and others. Dyspnea on exertion was graded by a Medical Research Council
      questionnaire, the examinee's self-assessment, and a more detailed 12-point scale
      questionnaire. Few persons had marked shortness of breath, and approximately one
      third had slight dyspnea. Individuals who had radiologic abnormalities
      experienced more shortness of breath than did those who had no radiologic
      abnormalities. Cigarette smoking also resulted in a higher prevalence of dyspnea.
      The results indicate that during the past, construction sheet-metal workers have
      been significantly exposed to asbestos on the job. Every effort should be made to
      minimize the anticipated serious health consequences, and further asbestos
      exposure for those who continue in this trade should be avoided.

PMID- 1992931
TI  - Selenium in forage crops and cancer mortality in U.S. counties.
AB  - The potential protective effect of selenium status on the risk of developing
      cancer has been examined in animal and epidemiologic studies. This ecological
      study investigated the association between U.S. county forage selenium status and
      site- and sex-specific county cancer mortality rates (1950-1969) using weighted
      least squares regression. Consistent, significant (p less than .01) inverse
      associations were observed for cancers of the lung, rectum, bladder, esophagus,
      and cervix in a model limited to rural counties and for cancers of the lung,
      breast, rectum, bladder, esophagus, and corpus uteri in a model of all counties.
      No consistent significant positive associations were observed in the rural county
      models. This remarkable degree of consistency for the inverse associations
      strengthens the likelihood of a causal relationship between low selenium status
      and an increased risk of cancer mortality.

PMID- 1992933
TI  - How many cancers are attributable to occupational exposures?

PMID- 1992932
TI  - Serum levels of bone Gla-protein in inhabitants exposed to environmental cadmium.
AB  - Serum levels of bone Gla-protein (BGP)--the vitamin K-dependent CA2(+)-binding
      protein--were evaluated in 76 cadmium (Cd)-exposed subjects with renal tubular
      dysfunction (32 men, 44 women) and 133 nonexposed subjects (53 men, 80 women).
      Serum BGP levels were higher in the Cd-exposed subjects than in nonexposed
      subjects. Significant correlations between BGP and each index measured by bone
      microdensitometry (MD), serum alkaline phosphatase activity, and Cd in blood and
      urine were found. For all of the Cd-exposed and nonexposed men and women, BGP
      showed a significant standard partial regression coefficient (multiple regression
      analysis) with the metacarpal index (MCI), which was one of the MD indicators.
      Bone Gla-protein also correlated significantly with urinary beta 2-microglobulin
      in the men and with serum creatinine in the women. Serum BGP values strongly
      reflect the degree of bone damage and also reflect, although less strongly, the
      degree of renal damage induced by exposure to Cd.

PMID- 1992934
TI  - Ambient level ozone effects on subpopulations of thymocytes and spleen T
      lymphocytes.
AB  - The effects of ozone on thymocyte and spleen T lymphocyte subpopulations were
      studied. Balb/c mice were exposed to clean air or to 0.3 +/- 0.05 ppm ozone for 1
      3 wk. Thymocytes and spleen T cells were stained with fluorochrome conjugated
      monoclonal antibodies against surface differentiation markers and/or propidium
      iodide for deoxyribonucleic acid (DNA). The cells were then analyzed by
      fluorescence activated cell sorter. The percentages of certain thymocyte and
      spleen T lymphocyte subtypes and DNA synthesizing spleen T cells were lower
      following 1 wk of ozone exposure. After 3 wk exposure, the thymocyte percentages
      were higher in ozone-exposed mice, whereas the absolute number remained lower,
      and spleen T lymphocytes showed no changes. The findings suggest that short-term
      ozone inhalation can affect the T cell immune system adversely, particularly the
      CD4+ cells.

PMID- 1992935
TI  - Proportion of lung and bladder cancers in males resulting from occupation: a
      systematic approach.
AB  - Studies conducted in several countries that investigated the relationship of
      occupation and cancer in men were reviewed and compared. Estimates of the
      proportion of cancers due to occupational exposure that occurred in the general
      population were analyzed, and sources of variation were explored. A systematic
      and standardized evaluation of studies on lung and bladder cancer were
      undertaken, and only investigations that allowed for confounding from tobacco
      smoking were included. The proportion of lung cancers attributable to occupation
      ranged between 1 and 5% (when considering only exposure to asbestos) and 40% (in
      a study with a high proportion of subjects exposed to ionizing radiation); for
      bladder cancer, estimates were between 0 and 3% in a few studies and between 16
      and 24% in several investigations. No similar attempt of systematic comparison
      was possible for other cancers.

PMID- 1992936
TI  - Rapid analysis of carcinoembryonic antigen levels in gallbladder bile.
      Identification of patients at high risk of colorectal liver metastasis.
AB  - Recently it was found that immunoanalysis of carcinoembryonic antigen (CEA)
      levels in gallbladder bile may be a sensitive method to detect colorectal liver
      metastases in humans. Methods used in the past for the detection of CEA in
      various body fluids were cumbersome and time consuming, requiring acid
      extraction, extensive dialysis, and column purification. Single-step, solid-phase
      radioimmunoassays, designed specifically for serum CEA analysis, were developed
      commercially to replace these methods. Parameters and methodology necessary to
      adapt these kits for Parameters and methodology necessary to adapt these kits for
      use with gallbladder bile are presented here. A combination of pretreatment
      procedures for bile, before radioimmunoassay, permit rapid, reproducible, and
      accurate measurement of CEA levels in gallbladder bile.

PMID- 1992937
TI  - Adenocarcinoma in Barrett's esophagus. A clinicopathologic study of 65 cases.
AB  - The natural history of Barrett's esophagus, particularly the prevalence and
      incidence of malignant changes in it, remains controversial. Furthermore the
      prognosis of surgically treated patients with carcinoma in Barrett's esophagus
      has not been elucidated fully. To examine these and other issues, the records of
      65 patients with carcinoma in Barrett's esophagus presenting at the Lahey Clinic
      Medical Center from January 1973 to January 1989 were reviewed. During this
      period, 241 patients with documented Barrett's esophagus were seen, for a
      prevalence of carcinoma of 27%. Adenocarcinoma in Barrett's esophagus accounted
      for 30% of the surgically treated carcinomas of the thoracic esophagus during
      this period. All but four of these patients were men. Symptoms of chronic reflux
      were present in less than one half of the patients and dysphagia was often the
      presenting symptom. In eight patients the carcinoma was discovered on routine
      surveillance endoscopy, and in four patients progression of disease from benign
      columnar epithelium to dysplasia to carcinoma was documented. Tumors developed in
      six patients who had undergone previous antireflux surgery, and in four other
      patients a second carcinoma developed in residual Barrett's epithelium after a
      previous resection. Of the 65 patients, 61 (94%) were considered to have operable
      disease, all of whom underwent resection. Two patients (3.3%) died within 30 days
      of operation. The resected specimens were staged as follows: stage 0, 4; stage I,
      10; stage II, 17; stage III, 25; stage IV, 4. Of the resected specimens, 73%
      showed areas of dysplasia adjacent to the tumor. The overall adjusted actuarial 5
      year survival rate was 23.7%. The 3-year survival rate was 100% for patients with
      stage 0 carcinoma, 85.7% for patients with stage I carcinoma, 53.6% for patients
      with stage IIA carcinoma, 45% for patients with stage IIB carcinoma, 25.2% for
      patients with stage III carcinoma, and 0% for patients with stage IV carcinoma.
      The premalignant nature of Barrett's esophagus requires endoscopic surveillance
      to detect early carcinoma because symptoms often occur late or are absent.
      Antireflux surgery does not protect against the development of carcinoma. All of
      the Barrett's epithelium must be resected because a second carcinoma may develop
      in residual columnar epithelium. Severe dysplasia should be considered an
      indication for resection. Although operability and resectability rates are high,
      long-term survival is not. Early detection is mandatory if long-term survival is
      to be achieved.

PMID- 1992938
TI  - Mastectomy following preoperative chemotherapy. Strict operative criteria control
      operative morbidity.
AB  - The surgical morbidity associated with aggressive preoperative chemotherapy in
      106 patients with advanced primary breast cancer who had chemotherapy followed by
      mastectomy was examined. These patients were compared with a group of 91
      consecutive patients who had mastectomy without preoperative chemotherapy. Strict
      operative criteria were used to determine the timing of mastectomy following
      chemotherapy. Wound infection rates were no different in the preoperative
      chemotherapy group compared to the mastectomy-alone groups (7% versus 4%; p =
      0.62). The incidence of wound necrosis was similar (11% versus 6%; p = 0.29).
      Seroma formation was decreased significantly in the preoperative chemotherapy
      group compared to the mastectomy-alone group (15% versus 28%; p = 0.04).
      Intensive preoperative chemotherapy did not delay the reinstitution of
      postoperative treatment (30% versus 20%; p = 0.27). However, when delay in
      instituting postoperative chemotherapy was more than 30 days, there was a
      significant decrease in overall survival rate (p = 0.04). This study provides
      evidence that intensive preoperative chemotherapy and mastectomy can be performed
      without increased morbidity. Furthermore it is important to institute systemic
      chemotherapy within 30 days of mastectomy to achieve maximum survival.

PMID- 1992939
TI  - Clinical outcome of seriously ill surgical patients with intra-abdominal
      infection depends on both physiologic (APACHE II score) and immunologic (DTH
      score) alterations.
AB  - The delayed-type hypersensitivity (DTH) response and the APACHE II score in 118
      patients with surgical infections were measured prospectively and related to
      outcome. Logistic regression analysis generated the equation: [formula: see
      text]. The risk assessment as calculated by this model was compared to that using
      the APACHE II system alone in a separate group of 354 patients. There was an
      improvement in the predictive capacity of the APACHE II + DTH equation compared
      to APACHE II alone, as shown by a better fit of expected and observed deaths, an
      improved Goodman-Kruskal G statistic, and a larger area under the receiver
      operating characteristic curve. It is concluded that the DTH response (a broad
      marker of immunocompetence) is an independent prognostic factor in surgical
      patients and can be used in combination with the APACHE II score (a measure of
      acute physiology) to estimate better the outcome of surgical patients.

PMID- 1992941
TI  - Organ procurement in patients with fatal head injuries. The fate of the potential
      donor.
AB  - A 46-month, retrospective review of all victims of fatal head injury at a level 1
      trauma center was undertaken to estimate donor organ availability, determine
      causes of procurement failure, and analyze the functional results of organs
      transplanted from this group of donors. Causes of procurement failure in 126
      patients who died principally from their head injuries included failure of
      initial resuscitation (14%), ineligibility (28%), failure of physiologic support
      (14%), and denial of consent (20%). Of 73 eligible donors, 29 (41%) were able to
      donate one or more vascular organs (heart, liver, kidney). In only one instance
      was an eligible donor not appropriately identified as such. Failure of
      physiologic support to prevent early death (25%), and denial of consent (34%)
      were found to be the two major, potentially remediable causes of procurement
      failure in this series. Based on this data, an estimated 29 patients/million
      population/year will survive initially and meet all eligibility requirements for
      organ donation. Data on 47 kidneys transplanted from the donor group demonstrated
      a 77% overall graft survival rate at a follow-up period averaging 23 months.
      Prolonged donor hypotension, but not the use of high-dose vasopressors, adversely
      affected allograft survival. The current limitations of organ procurement in
      victims of fatal head injury stem from a limited ability to maintain
      cardiopulmonary function long enough for the procurement process to be completed
      and a high overall rate (46%) of denial of consent for organ harvest by next of
      kin.

PMID- 1992940
TI  - The role of calcium ions and calcium channel entry blockers in experimental
      ischemia-reperfusion-induced liver injury.
AB  - Verapamil administered before treatment, but not after treatment, had a
      beneficial effect on a 90-minute warm ischemia-reperfusion rat liver injury
      model. The possible activation of proteases converting the xanthine dehydrogenase
      to xanthine oxidase, the significant mitochondrial calcium loading during the
      ischemic period, and the potentiation of calcium and oxygen-derived free radicals
      to promote injury to mitochondria are mechanisms supported by this study, based
      on both histologic observations and on the pattern of enzyme leak after the acute
      ischemic event.

PMID- 1992942
TI  - Transvaginal approach for repair of rectovaginal fistulae complicating Crohn's
      disease.
AB  - The management of rectovaginal fistulae complicating Crohn's disease is difficult
      and often unsatisfactory. Between December 1983 and November 1988, 13 patients
      with Crohn's disease underwent repair of rectovaginal fistulae via a transvaginal
      approach. All patients had a diverting intestinal stoma either as part of the
      initial step in the staged management of intractable perianal disease or
      concurrent with the repair of the rectovaginal fistula. Each of the patients had
      low or mid septal fistulae; high fistulae generally are treated transabdominally
      and are not the focus of this discussion. Fistulae were eradicated in 12 of the
      13 women and did not recur during the follow-up period, which averaged 50 months
      (range, 9 to 68 months). The only treatment failure was a patient who had a
      markedly diseased colon from the cecum to the rectum and a very low-lying
      fistula. It is concluded that a modified transvaginal approach is an effective
      method for repair of rectovaginal fistulae secondary to Crohn's disease.

PMID- 1992943
TI  - Glucose metabolism after pancreas autotransplantation. The effect of open duct
      versus urinary bladder drainage technique.
AB  - Glucose metabolism and insulin secretion after pancreas transplantation may be
      affected by the technique used for ductal drainage. We evaluated peripheral
      glucose and insulin levels after oral (oral glucose tolerance test [OGTT]) and
      sustained stable hyperglycemic challenge (clamp) in dogs who had undergone
      pancreas autotransplantation with intraperitoneal drainage (PAT) or with urinary
      bladder to pancreatic duct anastomosis (PAT/B). Both groups had basal glucose
      values comparable to normal controls; PAT/B animals had fasting hyperinsulinemia.
      Pancreas autotransplantation animals had an increased integrated glucose response
      to OGTT and blunted insulin response to hyperglycemic clamp. Urinary bladder to
      pancreatic duct anastomosis animals had a significantly decreased integrated
      glucose response to OGTT compared to PAT and an exaggerated insulin response to
      hyperglycemic challenge, which approximated normal control values by the last 30
      minute period of the clamp. Interestingly M values, which approximate glucose
      metabolized during the hyperglycemic challenge, were depressed in both surgical
      groups. It is concluded that the technique of bladder drainage allows a
      'normalization' of peripheral levels of insulin that is associated with
      amelioration of an altered glucose response after oral challenge. However the
      clamp studies show that, despite the improvement in insulin response, an
      insensitivity may exist to a wide range of endogenous levels after pancreas
      transplantation.

PMID- 1992945
TI  - 100 consecutive common duct exploration without mortality.

PMID- 1992944
TI  - Diets enriched with N-3 fatty acids ameliorate lactic acidosis by improving
      endotoxin-induced tissue hypoperfusion in guinea pigs.
AB  - The effect of 6 weeks dietary lipid manipulation on the acute physiologic
      response to 7-hour continuous endotoxin infusion in guinea pigs was examined. One
      diet was enriched with N-3 fatty acids, whereas the other contained N-6 fatty
      acids, primarily linoleic acid. Animals fed N-6 fatty acids developed significant
      lactic acidemia, microvascular muscle hypoperfusion, and pulmonary infiltrates in
      response to endotoxin infusion. N-3 fatty acid-fed animals demonstrated improved
      lactate levels, microvascular muscle perfusion, and lung morphology compared to N
      6 fatty acid-fed animals after endotoxin infusion. There was no significant
      change in cardiac output, PaO2, or mean arterial blood pressure at the end of the
      endotoxin infusion in either group. Pretreatment with indomethacin, or BM 13505,
      a specific thromboxane A2 receptor blocker, ameliorated the development of
      metabolic acidosis in N-6 fatty acid-fed animals, demonstrating a role for
      prostanoids in the sequelae of endotoxemia. The ability of dietary pretreatment
      with N-3 fatty acids to influence favorably the physiologic response to endotoxin
      represents a novel nutrient-metabolic interaction with potential therapeutic
      implications.

PMID- 1992946
TI  - Preoperative chemotherapy for soft-tissue sarcomas of the extremities.

PMID- 1992947
TI  - Carcinoembryonic antigen. New applications for an old marker.

PMID- 1992949
TI  - Living organ donation. Shifting responsibility.

PMID- 1992948
TI  - Splenic trauma. Choice of management.
AB  - The modern era for splenic surgery for injury began in 1892 when Riegner reported
      a splenectomy in a 14-year-old construction worker who fell from a height and
      presented with abdominal pain, distension, tachycardia, and oliguria. This report
      set the stage for routine splenectomy, which was performed for all splenic injury
      in the next two generations. Despite early reports by Pearce and by Morris and
      Bullock that splenectomy in animals caused impaired defenses against infection,
      little challenge to routine splenectomy was made until King and Schumacker in
      1952 reported a syndrome of "overwhelming postsplenectomy infection" (OPSI). Many
      studies have since demonstrated the importance of the spleen in preventing
      infections, particularly from the encapsulated organisms. Overwhelming
      postsplenectomy infection occurs in about 0.6% of children and 0.3% of adults.
      Intraoperative splenic salvage has become more popular and can be achieved safely
      in most patients by delivering the spleen with the pancreas to the incision,
      carefully repairing the spleen under direct vision, and using the many adjuncts
      to suture repair, including hemostatic agents and splenic wrapping.
      Intraoperative splenic salvage is not indicated in patients actively bleeding
      from other organs or in the presence of alcoholic cirrhosis. The role of splenic
      replantation in those patients requiring operative splenectomy needs further
      study but may provide significant long-term splenic function. Although
      nonoperative splenic salvage was first suggested more than 100 years ago by
      Billroth, this modality did not become popular in children until the 1960s or in
      adults until the latter 1980s. Patients with intrasplenic hematomas or with
      splenic fractures that do not extend to the hilum as judged by computed
      tomography usually can be observed successfully without operative intervention
      and without blood transfusion. Nonoperative splenic salvage is less likely with
      fractures that involve the splenic hilum and with the severely shattered spleen;
      these patients usually are treated best by early operative intervention.
      Following splenectomy for injury, polyvalent pneumococcal vaccine decreases the
      likelihood of OPSI and should be used routinely. The role of prophylactic
      penicillin is uncertain but the use of antibiotics for minor infectious problems
      is indicated after splenectomy.

PMID- 1992950
TI  - Lipids, vascular disease, and dementia with advancing age. Epidemiologic
      considerations.
AB  - Elevated plasma lipid and lipoprotein levels are associated with an increased
      risk of cardiovascular disease in middle-aged men and women. It is still not
      clear, however, whether lipid and lipoprotein abnormalities continue to be risk
      factors for cardiovascular disease in the elderly population. It is not even
      clear what normal lipid values are in the elderly, and whether diet or drug
      therapy should be advised on the basis of lipid values established in middle-aged
      populations. Ischemic heart disease does remain the leading cause of death in the
      elderly, and there is now preliminary evidence from epidemiologic studies that
      relative elevations of levels of lipid and lipoprotein fractions in an elderly
      population might be associated with an independent and increased risk of coronary
      heart disease, stroke, and possibly dementia. Intervention studies are about to
      begin that will assess various lipid-and lipoprotein-modifying therapies and
      their ability to reduce vascular disease risk in the elderly.

PMID- 1992951
TI  - Drug treatment of Alzheimer's disease.
AB  - Drugs may be part of the treatment for Alzheimer's disease. Drug treatment can be
      divided into two categories: treatment to improve cognitive function and
      treatment to improve abnormal behaviors. There are at least 16 new drugs
      undergoing evaluation that may improve cognitive function. Some of these drugs
      are intended to augment acetylcholine neurotransmitter function. Others are
      nootropics that affect neuron metabolism with little effect elsewhere. A third
      major category is drugs that affect brain vasculature. A miscellaneous group
      includes drugs aimed at modifying other defects found in Alzheimer's disease.
      Drugs to affect behavior have been available for some time. These include
      neuroleptics, anxiolytics, and antirage drugs. Use of all these drugs has been
      controversial. Recent federal legislation and guidelines affect their use in
      nursing homes. Specific indications for neuroleptics are psychotic features and
      agitation. Dosage for patients with dementia is different than for other
      psychotic patients. There is no consensus on the use of other psychoactive
      medications.

PMID- 1992952
TI  - The role of calcium channel blockers in the treatment of essential hypertension.
AB  - Calcium channel blockers, originally developed for the treatment of angina and
      supraventricular arrhythmias, have been shown to lower elevated blood pressure
      effectively in hypertensive patients. Verapamil, nifedipine, and diltiazem
      represent prototype compounds for unique chemical classes with differing
      pharmacologic properties. These drugs lower elevated blood pressure with efficacy
      comparable with other commonly used antihypertensives. Combination therapy with
      other agents usually results in an additive response. Side effects are usually
      mild and reversible and usually are an extension of the drug's pharmacologic
      effects. Moreover, adverse metabolic effects on lipid, glucose, or potassium
      levels are not common. Because of the excellent antihypertensive effects of
      calcium channel blockers and their potential importance in a variety of other
      disease states, these agents should be routinely considered for use as a first
      line antihypertensive agent in appropriately selected patients with hypertension
      of any severity as part of a comprehensive plan to minimize cardiovascular risk.

PMID- 1992953
TI  - Alanine aminotransferase in clinical practice. A review.
AB  - Alanine aminotransferase is an enzyme produced mainly in the liver. When serum
      activity is measured, it provides a marker of hepatic disease. This review
      explores the biochemistry and laboratory analysis of alanine aminotransferase in
      terms of its significance in human health and disease. Cut-off levels that define
      abnormality are rather arbitrary and this decreases the specificity of the test
      in apparently healthy patients. A small, but important, group of patients with
      alanine aminotransferase abnormality have underlying liver disease that may be
      treatable. Most can be diagnosed based on history, physical examination, and
      biochemical-serological profiles. Liver biopsy can complement the diagnostic
      process in selected circumstances. Literature pertaining to this is critically
      reviewed.

PMID- 1992954
TI  - Outcome of pregnancy in patients with systemic lupus erythematosus. A prospective
      study.
AB  - A prospective study was performed to investigate the outcome and complications of
      pregnancy in patients with systemic lupus erythematosus. Twenty-nine pregnancies
      occurred in 22 patients. There were 12 abortions, two spontaneous and 10 induced.
      Fifteen women had 17 live-born neonates. Neonatal complications included nine
      premature deliveries, two cases of intrauterine growth retardation, and one of
      Treacher Collins syndrome. Obstetric complications included threatened abortion
      (two), placenta previa (two), and preeclampsia (three). Cesarean sections were
      necessary in five patients. There was no maternal or neonatal mortality. Thirteen
      episodes of systemic lupus erythematosus relapses were detected by incidents of
      increasing proteinuria (six), arthritis (four), and vasculitic rash (two). There
      were no statistical differences in changes in hemoglobin level, erythrocyte
      sedimentation rate, albumin level, antinuclear antibody titer, or C3 or C4 level
      between the patients who relapsed and those who did not. Pregnancy could induce a
      flare of systemic lupus erythematosus in previously normal patients or patients
      with previously inactive disease. The overall neonatal and maternal survival was
      good, even in patients who presented during pregnancy. Spontaneous fetal loss was
      low (2/29 [6.9%]); both cases occurred in mothers with inactive lupus.

PMID- 1992955
TI  - Knowledge, attitudes, and behavior of elderly persons regarding living wills.
AB  - The knowledge, attitudes, and behavior of elderly persons regarding living wills
      were explored in a rural county in eastern North Carolina. A questionnaire was
      administered to 75 ambulatory elderly persons by personal interview at community
      dining sites. Fifty-two percent (39) of these subjects said they were familiar
      with living wills and 64% (48 persons) correctly summarized what the North
      Carolina living will says. When asked about preferences for medical care in the
      setting of a terminal illness, 86% (65 persons) stated a desire to receive basic
      medical care or comfort care only. Although their preferences were consistent
      with the provisions of a living will, none had signed the living will document
      provided by the state of North Carolina, and only two (3%) had discussed a living
      will with their physician. Seventy (93%) wanted their family or spouse to make
      decisions about terminal care if they themselves were unable to participate, and
      discussions between these persons and their chosen proxies actually occurred 45%
      (34/75) of the time. Eighty-one percent (61 persons) stated a desire to discuss
      end-of-life care with their physicians, but a minority (eight [11%]) had actually
      talked with their physicians, and these discussions were usually initiated by the
      patient (five of eight). We conclude that living will legislation is congruent
      with the desire of many elderly persons to limit medical care in terminal
      illness. However, this elderly population did not make use of living wills as a
      means of indicating their wishes. Recommendations are made to improve physician
      patient and patient-proxy communication regarding preferences for medical care at
      the end of life and living wills. Alternatives to the living will should also be
      explored.

PMID- 1992956
TI  - The decision to execute a durable power of attorney for health care and
      preferences regarding the utilization of life-sustaining treatments in nursing
      home residents.
AB  - One hundred three nursing home residents were interviewed regarding their
      preferences for the choice of an agent for health-care decision making while
      being offered the opportunity to execute a Durable Power of Attorney for health
      care. They also completed a questionnaire that tapped their preferences regarding
      the use of four types of life-support treatment under three hypothetical levels
      of future cognitive functioning. Factors that might influence these preferences,
      such as previous experiences with life-sustaining treatments, religious beliefs,
      and personal values, were also examined. Participants tended to choose their son
      or daughter as their agent for future health-care decision making. They had clear
      and consistent patterns of preferences regarding the utilization of life
      sustaining treatment. Generally, participants opted not to be treated, although
      there was variability among participants. They were even less inclined to opt for
      treatment as their perceived level of future cognitive functioning declined, or
      when the life-sustaining treatment involved permanent rather than temporary
      procedures.

PMID- 1992957
TI  - Comparative study of a microporous cholestyramine analogue (filicol) and
      gemfibrozil for treatment of severe primary hypercholesterolemia. Short- and long
      term results.
AB  - The hypolipidemic effect of gemfibrozil in severe hypercholesterolemia is not
      well established. Fifty patients with primary hypercholesterolemia (including 18
      patients with familial hypercholesterolemia) and stable low-density lipoprotein
      cholesterol levels greater than 3.90 mmol/L (greater than 150 mg/dL) (6.10 +/-
      1.30 [SD] mmol/L; 236 +/- 50 mg/dL) while on a hypolipidemic diet were assigned
      to treatment for 12 weeks with either 9 g/d of filicol, a microporous
      cholestyramine analogue, or 1.2 g/d of gemfibrozil in a randomized clinical
      trial. Tolerance was good with both drugs. Filicol and gemfibrozil caused similar
      decrements of total cholesterol (14% for both), low-density lipoprotein
      cholesterol (20% and 18%, respectively), and apolipoprotein B (16% and 21%,
      respectively). Close to 40% of the patients had decreases of greater than 25% in
      low-density lipoprotein cholesterol levels with both drugs. Gemfibrozil, but not
      filicol, significantly increased plasma high-density lipoprotein cholesterol
      (16%) and apolipoprotein A-I (17%) levels and reduced triglyceride levels (35%).
      No loss of efficacy was observed with either drug in subsets of patients who had
      a good 12-week response rate and had extended therapy for up to 12 months. This
      study demonstrates that gemfibrozil may have a beneficial effect on all aspects
      of the plasma lipid profile in patients with severe hypercholesterolemia, a
      clinical situation where it can be used with potential advantages over standard
      doses of anion-exchange resins.

PMID- 1992958
TI  - Adult overwhelming meningococcal purpura. A study of 35 cases, 1977-1989.
AB  - The study objective was to describe the clinical, biologic, and hemodynamic
      features of adult overwhelming meningococcal purpura and to examine the
      prognostic factors by multivariate analysis at the time of admission to the
      intensive care unit. Thirty-five patients (greater than or equal to 13 years of
      age) with meningococcal infection, circulatory shock, and generalized purpuric
      lesions of abrupt onset were recorded in eight intensive care units from 1977 to
      1989. The patients were young (mean age, 26.6 years; range, 13 to 68 years) and
      had been previously healthy. The female-to-male ratio was 3:1. Mortality was
      54.3%, with most deaths occurring within the first 48 hours, usually secondary to
      irreversible shock with multiple organ failure. Ischemic complications (eight
      cases), prolonged heart failure (seven cases), and secondary septicemia (five
      cases) were the chief complications among survivors. Initial hemodynamic study
      after volume loading showed low stroke volume index (mean +/- SD, 29.4 +/- 13
      mL/m2) and tachycardia (mean +/- SD, 138 +/- 16 beats per minute), a profile
      suggesting a greater myocardial depression than usually observed in gram-negative
      bacillary septic shock. Univariate prognostic analysis showed that four variables
      at the time of admission were associated with fatal outcome: a plasma fibrinogen
      level of 1.5 g/L or less, a factor V concentration of 0.20 or less, a platelet
      count lower than 80 x 10(9)/L, and a cerebrospinal fluid leukocyte count of 20 x
      10(6)/L or less. Stepwise regression analysis showed that low fibrinogen level
      (less than or equal to 1.5 g/L) was the sole adverse prognostic variable (odds
      ratio = 2, 95% confidence interval, 1.5 to 2.7). Adult overwhelming meningococcal
      purpura is still associated with high mortality and morbidity. Low fibrinogen
      level at time of admission may permit early recognition of the most severely ill
      patients.

PMID- 1992959
TI  - Increased serum aluminum. An independent risk factor for mortality in patients
      undergoing long-term hemodialysis.
AB  - The annual mortality rate among patients receiving long-term hemodialysis has
      been rising over the past decade. The prevalences of known risk factors such as
      older age, male sex, duration of dialysis, presence of diabetes, coronary artery
      disease, or hypertension do not seem to have changed during this time. However,
      evidence suggests that an increased body aluminum level may have an adverse
      effect on survival even in the absence of overt aluminum toxic reaction.
      Therefore, we evaluated the correlation between serum aluminum levels and
      mortality in 10 646 patients undergoing long-term hemodialysis. Mortalities were
      18% higher for patients with serum aluminum levels between 1520 and 2220 nmol/L
      and progressively increased to 60% higher for patients with aluminum levels above
      7410 nmol/L. Serum aluminum level was an important predictor of survival even
      after other known risk factors had been controlled. These data strongly suggest
      that patients undergoing long-term hemodialysis should have periodic surveillance
      of the serum aluminum levels, and in those patients who have plasma levels of
      1520 to 2220 nmol/L or higher, one should seriously consider discontinuing
      aluminum salts and giving therapy to decrease body aluminum level if it is found
      to be increased.

PMID- 1992960
TI  - Sensitivity of exercise electrocardiography for acute cardiac events during
      moderate and strenuous physical activity. The Lipid Research Clinics Coronary
      Primary Prevention Trial.
AB  - We determined whether the exercise electrocardiogram predicted acute cardiac
      events during moderate or strenuous physical activity among 3617 asymptomatic,
      hypercholesterolemic men (age range, 35 to 59 years) who were followed up in the
      Coronary Primary Prevention Trial. Submaximal exercise test results were obtained
      at entry and at annual follow-up visits in years 2 through 7. ST-segment
      depression or elevation (greater than or equal to 1 mm or 10 microV-sec) was
      considered to be a positive test result. The circumstances that surrounded each
      nonfatal myocardial infarction and coronary heart disease death were determined
      through a record review. The cumulative incidence of activity-related acute
      cardiac events was 2% during a mean follow-up period of 7.4 years. The risk was
      increased 2.6-fold in the presence of clinically silent, exercise-induced, ST
      segment changes at entry (95% confidence interval [Cl], 1.3 to 5.2) after
      adjustment for 11 other potential risk factors. Of 62 men who experienced an
      activity-related event, 11 had a positive test result at entry (sensitivity, 18%;
      95% Cl, 8 to 27). The specificity of the entry exercise test was 92% (95% Cl, 91
      to 93). The sensitivity and specificity were similar when the length of follow-up
      was restricted to 1 year after testing. For a newly positive test result on a
      follow-up visit, the sensitivity was 24% (95% Cl, 12 to 36), and the specificity
      was 85% (95% Cl, 84 to 86); for any positive test result during the study (mean
      number of tests per subject, 6.2), the sensitivity was 37% (95% Cl, 25 to 49),
      and the specificity was 79% (95% Cl, 77 to 80). Our findings suggested that the
      presence of clinically silent, exercise-induced, ischemic ST-segment changes on a
      submaximal test was associated with an increased risk of activity-related acute
      cardiac events. However, this test was not sensitive when used to predict the
      occurrence of activity-related events among asymptomatic, hypercholesterolemic
      men. For this reason, the utility of the submaximal exercise test to assess the
      safety of physical activity among asymptomatic men at risk of coronary heart
      disease is likely to be limited.

PMID- 1992961
TI  - Deleterious effects of criminal victimization on women's health and medical
      utilization.
AB  - The long-term consequences of criminal victimization on physical health were
      examined among 390 adult women (74 nonvictims and 316 victims of crime). Data
      included health status self-ratings and objective service utilization. Findings
      indicated that severely victimized women, compared with nonvictims, reported more
      distress and less well-being, made physician visits twice as frequently in the
      index year, and had outpatient costs that were 2.5 times greater. Criminal
      victimization severity was the most powerful predictor of physician visits and
      outpatient costs. Utilization data across 5 years preceding and following crime
      were obtained from 15 rape victims, 26 physical assault victims, and 27
      noncontact crime victims and were compared with five continuous years of
      utilization among 26 nonvictims. Victims' physician visits increased 15% to 24%
      during the year of the crime compared with less than 2% change among nonvictims.
      We conclude that these long-term deleterious effects suggest that criminally
      victimized women's needs for medical treatment transcend the traditional focus on
      emergency care and forensic evaluation.

PMID- 1992962
TI  - Ventricular tachycardia during routine treadmill testing. Risk and prognosis.
AB  - Exercise-induced ventricular tachycardia during exercise testing is considered to
      increase risk during testing. Moreover, exercise-induced ventricular tachycardia
      has been considered to confer a poor prognosis although this has not been
      specifically studied. On a retrospective review of 3351 patients who had
      undergone routine clinical exercise testing between September 1984 and June 1989,
      we identified 55 patients with exercise-induced ventricular tachycardia. The mean
      follow-up was 26 months (range, 2 to 58 months). Fifty patients had nonsustained
      ventricular tachycardia during exercise testing and one of these patients died
      due to congestive heart failure during the follow-up period. Five patients had
      sustained ventricular tachycardia during exercise testing and one died suddenly 7
      months after the test. Ventricular tachycardia was reproduced in only two of the
      29 patients who underwent repeated exercise testing. Ventricular tachycardia
      during routine clinical exercise testing occurred rarely (prevalence of 1.5%) and
      was not associated with complications during testing. The total mortality in the
      exercise-induced ventricular tachycardia group (3.6%) was not significantly
      different from the mortality in the entire population (5.1%). Nonsustained
      ventricular tachycardia occurring during clinical exercise testing is not an
      independent marker of a poor prognosis.

PMID- 1992963
TI  - Short-term changes in renal function, blood pressure, and electrolyte levels in
      patients receiving cyclosporine for dermatologic disorders.
AB  - We compared the changes in renal function, blood pressure (BP), and
      concentrations of serum potassium, magnesium, and urate (uric acid) in two groups
      of patients not given transplants. Group 1, comprising 21 psoriatic patients, was
      treated with 14 mg/kg per day of oral cyclosporine for 4 weeks in a prospective,
      placebo-controlled study; group 2, comprising 28 patients with diverse cutaneous
      diseases, was given 6 mg/kg per day of oral cyclosporine for 1 to 3 months in a
      prospective, open-labeled study. Renal function (determined by serum urea
      nitrogen [SUN] and creatinine levels and urinalysis), BP, serum electrolyte
      levels (potassium and magnesium), and urate level were measured weekly for the
      first 4 weeks in both groups, and then, after 2 and 3 months of therapy, in group
      2 only. During the first 4 weeks in group 1 patients, there were significant
      increases in values of SUN, creatinine, BP, potassium, and urate, and a
      significant decrease in the serum magnesium value. When data for the two groups
      were combined, the changes from pretherapy values in each of the above measures
      (except systolic BP) during the first 4 weeks correlated significantly with
      cyclosporine trough levels. In group 2, the changes that occurred in the first 4
      weeks in the SUN value, SUN/creatinine ratio, and BP were magnified over the
      subsequent 8 weeks of treatment. In the combined group for the first 4 weeks of
      therapy, duration of therapy, independent of cyclosporine trough levels,
      correlated with changes in SUN, creatinine, and urate levels, but not with
      changes in the potassium or magnesium level or in BP. We conclude that the
      cyclosporine blood level was a better discriminant than cyclosporine dosage in
      the analysis of renal dysfunction and hypertension in these patients.

PMID- 1992964
TI  - A population-based study of functional status and social support networks of
      elderly patients newly diagnosed with cancer.
AB  - We assessed the functional status and social support networks of 799 men and
      women aged 65 years or older newly diagnosed with cancer and living in six New
      Mexico counties. Functional limitations included depending on others for
      transportation (33%) and mental incompetence or poor recent memory (42%). The
      percentage of patients with functional limitation increased sharply with
      increasing age. In a substantial number of patients there was also evidence for
      poor social support networks; 26.5% of subjects lived alone and 38.9% had no
      children living in the vicinity. In a multiple logistic regression analysis, the
      predictors of having a poor social support network included non-Hispanic white
      ethnicity, advanced age, low income, and being a recent migrant to the area.
      Subjects with functional limitations were more likely to have poor social support
      networks than subjects without such limitations. The deleterious combination of
      impaired functional status and a limited social support network may explain why
      elderly cancer patients are at increased risk for not receiving appropriate
      therapy. Given the potential complexities involving the evaluation and
      appropriate treatment of cancer, care must be taken to adequately assess
      functional status and support mechanisms of older patients, and to provide
      adequate support to ensure compliance with treatment.

PMID- 1992965
TI  - Giant cell arteritis. A case with unusual neurologic manifestations and a normal
      sedimentation rate.
AB  - Giant cell (temporal) arteritis is a serious inflammatory condition that can lead
      to blindness, stroke, or other adverse sequelae if not properly treated. An
      elevated erythrocyte sedimentation rate has traditionally been emphasized as a
      criterion for making this diagnosis. Delays in diagnosis and unnecessary testing
      may occur when a patient presents with a normal erythrocyte sedimentation rate
      and a clinical history consistent with this condition. We describe a patient with
      giant cell arteritis who presented with a normal erythrocyte sedimentation rate
      and who subsequently developed devastating central nervous system complications.

PMID- 1992966
TI  - Ototoxic reaction to erythromycin.
AB  - We report a case of bilateral hearing loss in a patient treated with intravenous
      erythromycin lactobionate. The ototoxic reaction occurred despite the patient's
      having normal renal and hepatic function and the fact that serum erythromycin
      levels were within the predicted normal range. In addition to hearing loss, a
      marked labyrinthic hyporreflexia was also observed. Hearing loss improved after
      the treatment was discontinued, but labyrinthic abnormalities persisted
      suggesting that erythromycin had caused a permanent vestibular damage.

PMID- 1992967
TI  - A severe multisystem reaction to sulindac.
AB  - We present a case of a severe reaction to sulindac. A 30-year-old woman with
      quiescent systemic lupus erythematosus received sulindac for nonspecific
      migrating chest pain. An initial course of therapy produced an unrecognized
      sensitization to the drug with a febrile illness and rash. Readministration of
      the drug caused an anaphylactoid reaction as well as evidence of cardiovascular,
      hepatic, pulmonary, and hematologic dysfunction. The patient's illness had
      evidence of types I, II, and III hypersensitivity reactions.

PMID- 1992969
TI  - Smoking and the risk of gallstones.

PMID- 1992970
TI  - A positive family history of breast cancer and benign breast disease: does its
      effect diminish with age?

PMID- 1992968
TI  - Occlusive vasculopathy in systemic lupus erythematosus. Association with
      anticardiolipin antibody.
AB  - Patients with systemic lupus erythematosus and with antiphospholipid antibody are
      subject to sudden occlusion of multiple blood vessels. We describe two patients
      with systemic lupus erythematosus with acute, catastrophic, widespread non
      inflammatory visceral vascular occlusions associated with high-titer
      antiphospholipid antibody. The histopathologic features clearly distinguished
      these patients from classic systemic lupus erythematosus vasculitis. We further
      suggest that, based on a probable pathogenesis related to the presence of
      antiphospholipid antibody, and based on the non-inflammatory vascular occlusion,
      steroids and other immunosuppressive medications are of limited value.
      Plasmapheresis along with anticoagulant therapy should be considered.

PMID- 1992971
TI  - 'Laughing all the way to the bank.

PMID- 1992972
TI  - Enalapril and reversible alopecia.

PMID- 1992973
TI  - BASIC microcomputer program for generating percentile values, based on age and
      serum cholesterol levels.

PMID- 1992975
TI  - Cancer patient staging. A perspective.

PMID- 1992974
TI  - The origin of epidermal melanocytes. Implications for the histogenesis of nevi
      and melanomas.
AB  - Among the most venerable concepts in dermatopathology is Unna's 19th century
      notion of Abtropfung, ie, that melanocytes drop off from the epidermis to the
      dermis during the histogenesis of melanocytic tumors. Paradoxically, however,
      Unna's basic premise of an epidermal origin for melanocytes has been seriously
      questioned for over 40 years, based on experimental evidence favoring a neural
      crest origin for melanocytes. Recent work has strengthened the evidence for a
      neural crest origin of epidermal melanocytes, and it has been suggested that the
      concept of Abtropfung be replaced by the concept of Hochsteigerung. The concept
      of Hochsteigerung holds that melanocytes migrate up from the dermis into the
      epidermis-not only in normal development, but also during normal tissue
      maintenance. It now seems likely that the precursor of melanocytes, in both
      normal and abnormal differentiation, may not be a melanoblast (a primitive cell
      committed to melanocytic differentiation) but rather a pluripotential cell.
      Although axon-investing Schwann cells have been the traditional focus as the
      closest relative of the epidermal melanocyte, recent studies suggest that another
      nerve sheath cell, the perineural cell, might be a better candidate. These
      concepts have profound implications for the histogenesis of melanocytic nevi and
      melanomas.

PMID- 1992976
TI  - Recurrent pigmented melanocytic nevus. A benign lesion, not to be mistaken for
      malignant melanoma.
AB  - Melanocytic nevi that recur after incomplete removal are pigmented lesions that
      may clinically and pathologically simulate malignant melanoma in situ. Five
      examples of recurrent pigmented melanocytic nevus, with emphasis on light
      microscopic and immunohistochemical findings, are reported herein. Prominent HMB
      45 staining in these nevi may cause further confusion in differentiating them
      from malignant melanoma. The differential diagnosis of recurrent pigmented
      melanocytic nevi is discussed, with particular emphasis on distinguishing these
      lesions from malignant melanoma. Our immunohistochemical observations indicate
      that the recurrences most likely develop as a result of proliferation of
      melanocytes remaining in the epidermis and/or adnexae following incomplete
      removal. The approach and management of recurrent nevi are also discussed.

PMID- 1992978
TI  - Two distinct types of intraneuronal neurofibrillary tangles highlighted by
      polarized light after silver impregnation with a modified Bielschowsky method.
AB  - Neurofibrillary tangles (NFTs) are one of the morphological hallmarks of
      Alzheimer's disease. The birefringency and dichroism of NFTs following congo red
      staining have long been known. Herein, we report the observation that a subset of
      NFTs show distinct birefringency induced by a modified Bielschowsky silver
      impregnation method. Birefringency of NFTs could not be elicited after silver
      impregnation with one other version of the Bielschowsky method or with the Bodian
      technique. To our knowledge, these properties of NFTs after metal impregnation
      have not been previously documented.

PMID- 1992977
TI  - Pulmonary tumor embolism to alveolar septal capillaries. A prospective study of
      12 cases.
AB  - Pulmonary tumor embolism leading to subacute cor pulmonale has been extensively
      studied. However, to our knowledge, the involvement of pulmonary alveolar
      capillaries has not previously been studied in detail. A prospective study was
      conducted on 112 autopsied patients with cancer to determine the presence of
      microembolism in the alveolar septal capillaries. Fifteen sections of
      predetermined lung areas were obtained and examined. Tumor embolism to alveolar
      septal capillaries was detected in 12 cases (10.7%), with simultaneous
      involvement of other vascular territories in 11. Seven patients had dyspnea;
      four, right ventricular failure; four, hypertrophy of the right ventricle; and
      three, arterial vascular sclerosis. The present data have led us to conclude that
      pulmonary tumor embolism to alveolar septal capillaries occurs in association
      with the involvement of arterial or lymphatic vessels and should be analyzed
      within the context of the study of subacute cor pulmonale.

PMID- 1992979
TI  - Secretory carcinoma of the breast.
AB  - Most studies of secretory carcinoma of the breast have been single case reports
      or separate analyses of the problem in either children or adults. We studied 10
      female patients, aged 5 to 87 years. Most patients presented with a palpable
      mass, often near the areola. Five of six tumors were estrogen receptor negative;
      three analyzed for progesterone receptor were positive. Histologic patterns
      present in varying proportions were "classic" secretory carcinoma with
      microacini, abundant secretion with papillary features, and with prominent solid
      and papillary apocrine features. The tumors had strong reactivity for alpha
      lactalbumin, S100, and carcinoembryonic antigen (polyclonal) and were negative
      for gross cystic disease fluid protein and anti-carcinoembryonic antigen
      (monoclonal). Six patients had mastectomy; four had local excision; none had
      axillary nodal metastases initially. With follow-up of 3 to 72 months (mean, 47
      months; median, 48 months), two patients treated by local excision had local
      recurrences, one patient had axillary nodal metastases. All patients are alive.
      Comparison of patients under and over 30 years of age revealed one important
      difference: younger patients had a longer interval between detection and biopsy
      30 vs 2 months. Treatment recommendations are initial wide excision or
      quadrantectomy with low axillary dissection in most cases and, in premenarchal
      patients, strong effort to preserve the breast bud without jeopardizing local
      control.

PMID- 1992980
TI  - Intraluminal crystalloids in struma ovarii. Immunohistochemical, DNA flow
      cytometric, and ultrastructural study.
AB  - We recently encountered a unique case of follicular variant of papillary
      carcinoma arising in struma ovarii that contained numerous intrafollicular
      crystalloids. There was no evidence of capsular or vascular invasion or
      metastases, though the DNA content of the papillary carcinoma was aneuploid. In
      contrast, diploid DNA was manifested in the histologically benign thyroid tissue.
      The nature of the crystalloids and the significance of aneuploid DNA content are
      discussed.

PMID- 1992981
TI  - Steroid cell tumor of the ovary in a child.
AB  - An 8-year-old girl exhibited severe, progressive virilization of 2 years'
      duration associated with markedly elevated circulating testosterone
      concentrations. Based on her initial clinical presentation and results of a
      chemical evaluation, she was originally thought to have non-classic 21
      hydroxylase deficiency, but her condition did not respond to corticosteroid
      therapy. Further evaluation confirmed the presence of an ovarian neoplasm. The
      excised ovary contained an attached gray-brown mass. Light microscopic and
      ultrastructural examination revealed the mass to be a steroid cell tumor. Because
      Reinke's crystals were not present, it was designated to be a steroid cell tumor
      not otherwise specified. This case represents one of 22 reported cases of steroid
      cell tumor occurring in children described in the literature, most of which have
      been associated with heterosexual precocity. To our knowledge, steroid cell
      tumors are benign when they occur in prepubertal children. Although they are
      rare, steroid cell tumors of the ovary should be considered in cases of childhood
      virilization.

PMID- 1992982
TI  - Cold-induced granulocyte agglutination. A cause of pseudoleukopenia.
AB  - Transient cold agglutination of her granulocytes developed in a 60-year-old woman
      with a left upper lobe pneumonia during the acute phase of her illness. This
      phenomenon was manifested by pseudogranulocytopenia, multiple clumps of
      granulocytes on her peripheral blood smear, and abnormal distribution of
      granulocytes and monocytes on the white blood cell histogram when measured on an
      automated hematology analyzer (Coulter S-Plus IV, Coulter Electronics Inc,
      Hialeah, Fla). The cause is postulated to be an IgM autoantibody directed against
      components of the granulocyte membranes. Spurious leukopenia is encountered
      infrequently with automated hematology analyzers. Cold-induced granulocyte
      agglutination should be recognized as a potential cause of pseudogranulocytopenia
      so that white blood cell counts can be accurately reported and unnecessary
      evaluation of patients for leukopenia can be avoided.

PMID- 1992983
TI  - Gross cystic disease fluid protein-15 in salivary gland tumors.
AB  - Gross cystic disease fluid protein-15 (GCDFP-15) is a 15-kd glycoprotein that is
      expressed by normal apocrine epithelia and in a majority of breast carcinomas.
      However, recent studies have demonstrated that this substance is also present in
      tumors of the salivary glands, sweat glands, and prostate gland. To determine
      whether the expression of CGDFP-15 might aid in the differential diagnosis of
      salivary gland lesions, the anti-GCDFP-15 monoclonal antibody D6 was applied to
      paraffin sections of 133 such neoplasms. Benign tumors (76% reactive) were more
      often labeled than malignant lesions (28% reactive) by this antibody; overall, 53
      (41%) of 133 cases were positive for GCDFP-15. Notably, the tubuloglandular
      components in 17 (81%) of 21 pleomorphic adenomas were reactive, but no example
      of either adenoid cystic carcinoma or polymorphous low-grade adenocarcinoma were
      labeled. In contrast, 24% of adenocarcinomas stained with this antibody. The
      apparent expression of GCDFP-15 by a spectrum of salivary gland tumors supports
      their biologic relationship to lesions of the cutaneous apocrine glands and
      breast. Furthermore, the demonstration of this determinant may be of use in
      suggesting the salivary gland nature of poorly differentiated carcinomas of the
      head and neck, and it may facilitate the separation of pleomorphic adenoma from
      histologically similar malignant neoplasms in the salivary glands themselves.

PMID- 1992984
TI  - Interference by iatrogenically induced anti-mouse IgG antibodies in a two-site
      immunometric assay for thyrotropin.
AB  - Two-site immunometric assays using mouse monoclonal antibodies are gaining
      increasingly widespread popularity and use. Patients with circulating antimurine
      immunoglobulin antibodies capable of interfering in these assays have been
      encountered and described sporadically. Parenteral administration of murine
      monoclonal antibodies for imaging and therapeutic purposes is increasing and is
      known to induce human anti-murine antibodies frequently. We examined 60 serum
      samples from 48 individuals who received such murine immunoglobulin to determine
      whether iatrogenically induced anti-murine antibodies could interfere in a two
      site (sandwich) immunoradiometric assay for serum thyrotropin. We found that
      these circulating antibodies can indeed interfere in an "unblocked" assay, but
      that the interference appears to be suppressed by including nonspecific IgG in
      the commercial version of the assay kit.

PMID- 1992985
TI  - The tall cell variant of papillary carcinoma of the thyroid gland. Comparison
      with the common form of papillary carcinoma by DNA and morphometric analysis.
AB  - The tall cell variant of papillary carcinoma of the thyroid manifests a more
      aggressive behavior than the usual form of papillary carcinoma of the thyroid.
      Morphometric analysis of nuclear features and DNA analysis may yield information
      predictive of aggressive behavior. Accordingly, the DNA content and morphometric
      features of the neoplastic cells of the tall cell variant were measured and
      compared with measurements obtained from neoplastic cells of the usual form of
      papillary carcinoma. Six of the 11 tall cell neoplasms were aneuploid, as were
      four of the eight usual papillary neoplasms. Although benign cells were separated
      from malignant cells in each case, differences between tall and usual papillary
      carcinoma cells were not observed regarding DNA content, chromatin texture, or
      nuclear size and shape. Differences in the clinical behavior of these neoplasms
      will likely need to be explained on the basis of other characteristics.

PMID- 1992987
TI  - Ring neutrophils in plasma cell dyscrasia.
AB  - Sporadic reports in the medical literature concern the significant incidence of
      neutrophils with ring-shaped nuclei in myeloproliferative disorders. We report
      our first encounter with ring neutrophils in patients with lymphoproliferative
      disorders. A significant incidence of ring neutrophils was observed in all of 20
      patients with multiple myeloma and in nine of 10 patients with monoclonal
      gammopathy of undetermined significance. The mean percent of ring neutrophils was
      9.5% (range, 1.0% to 28.0%) in patients with multiple myeloma, which was
      significantly greater than in those with monoclonal gammopathy of undetermined
      significance or in healthy controls. In multiple myeloma, the incidence of ring
      neutrophils in the pretreatment phase was greater than that in the remission
      phase. A great deal of overlap was noted between multiple myeloma in the
      remission phase and monoclonal gammopathy of undetermined significance. The
      incidence of ring neutrophils seemed to vary according to disease stage. Ring
      neutrophils may reflect abnormal granulopoiesis in plasma cell dyscrasias.

PMID- 1992986
TI  - Squamous cell carcinoma in situ arising in an ovarian mature cystic teratoma.
      Report of one case with histopathologic, cytogenetic, and flow cytometric DNA
      content analysis.
AB  - A squamous cell carcinoma in situ arose in an ovarian mature teratoma (ie,
      dermoid cyst) in a 62-year-old woman. Flow cytometric DNA content analysis of
      paraffin-embedded in situ carcinoma showed a normal DNA content with moderate to
      high proliferative activity (S-phase fraction estimate, 16% to 18%). Cytogenetic
      analysis of the in situ cancer and the benign cystic portion of the tumor
      revealed a 46,XX karyotype. In addition, the benign cystic portion of the tumor
      revealed homozygous chromosomal heteromorphisms, compared with heterozygous
      markers found in peripheral blood lymphocytes. These results show that this
      squamous cell carcinoma in situ was euploid and suggest that the mature cystic
      teratoma was derived from a single germ cell after meiosis I.

PMID- 1992988
TI  - Reference ranges for lymphocyte subsets. A comparison of standard vs rapid whole
      blood lysis techniques.
AB  - Reference ranges for lymphocyte subsets may vary with processing techniques,
      monoclonal reagents, or analytic methods. We compared reference ranges obtained
      for T- and B-lymphocyte subsets by means of standard manual whole-blood lysis
      with a wash step vs a rapid, no-wash whole-blood lysis system. Both techniques
      demonstrated reference ranges similar to those in previous literature reports.
      The ranges established with standard and rapid lysis were similar when antibodies
      directed to the same cluster designation were used. Although slight statistical
      differences in relative percentages of CD2 and CD3 lymphocytes were observed,
      these differences were probably not clinically significant. These data indicate
      that the rapid technique provides a standardized method for enumerating T and B
      lymphocytes in peripheral blood.

PMID- 1992989
TI  - The anatomy of a gene. C-myc.

PMID- 1992990
TI  - Cholecystectomy and hepatic artery injuries.
AB  - This study included 71 cadavers used for anatomical dissection that had undergone
      cholecystectomies. Of these five, 7% had some type of hepatic artery injury. The
      subjects all had survived at least 1 year after cholecystectomy and had normal
      livers. The mechanisms of this injury, its pathophysiology, and its prevention
      are discussed.

PMID- 1992991
TI  - Humoral immunity in surgical patients with and without trauma.
AB  - We measured antitetanus toxoid antibody responses after blunt (n = 24) and
      penetrating (n = 7) trauma and compared them with responses in patients without
      trauma (n = 55). Patients were defined as anergic or reactive on the basis of
      delayed type hypersensitivity response. The response to tetanus toxoid
      vaccination on admission of patients surviving trauma for over 2 weeks was
      defined as the ratio of day 14 to day 0 serum IgG antitetanus toxoid levels.
      Antitetanus toxoid responses were normal after both blunt and penetrating trauma.
      When stratified according to delayed type hypersensitivity responses, patients
      with trauma showed better antibody responses than patients without trauma. Major
      infection rates were similar between trauma groups (three of 24 with blunt trauma
      vs two of seven with penetrating trauma) and independent of delayed type
      hypersensitivity (two of 20 reactive patients vs three of 11 anergic patients),
      in contrast to patients without trauma (one of 19 reactive patients vs 15 of 36
      anergic patients). We conclude that decreased delayed type hypersensitivity after
      moderate trauma is temporary, and that this transient immunodeficiency is not as
      strongly associated with reduced antibody responses and increased risk of
      infection as anergy in surgical patients without trauma.

PMID- 1992992
TI  - Clinical spectrum of fungal infections after orthotopic liver transplantation.
AB  - During a 50-month period, we identified 91 episodes of fungal infection in 72
      liver transplant recipients (23.8%). Candida species accounted for 83.5% of
      cases. Clinical patterns of fungal infections included disseminated infection
      (19), peritonitis (17), pneumonitis (15), multiple sites of colonization (13),
      fungemia (11), and other sites (16). The diagnosis of fungal infection was
      usually made in the first 2 months (84.7% of cases), at a mean time of 16 days
      after transplantation. Risk factors for fungal infections included
      retransplantation, Risk score, intraoperative transfusion requirement, urgent
      status, Roux limb biliary reconstruction (in adults), steroid dose, bacterial
      infections and antibiotic therapy, and vascular complications. Fungal infections
      were successfully treated with amphotericin B in 63 cases (74.1%) but were
      associated with diminished patient survival (50% vs 83.5%). Fungal infection is a
      frequent source of early morbidity and can be related to well-defined risk
      factors, suggesting the need for effective prophylaxis.

PMID- 1992993
TI  - Transient and distant infections alter later intraperitoneal abscess formation.
AB  - Transient nosocomial infections, such as line sepsis and pneumonia, are common in
      today's critical care patient population. Although generally well treated, the
      effect of these transient antigen exposures on the immune system is unclear. We
      have previously shown that prior intraperitoneal inoculation with live bacteria
      leads to increased numbers of intraperitoneal abscesses. Data presented here
      demonstrate in a murine model that two immunizations with live Escherichia coli,
      Bacteroides fragilis, or both, administered systemically via intracardiac
      injection or at a focal distant site in subcutaneous tissue, significantly
      increased the number of mixed E coli/B fragilis intraperitoneal abscesses when
      induced 1 week later. Further, immunization with E coli, either alone or in
      combination with B fragilis, increased the total number of anaerobes recovered
      per mouse. Transient or focal sublethal infections can significantly alter an
      animal's immune response to later infectious insults, particularly the formation
      of intraperitoneal abscesses.

PMID- 1992994
TI  - Pneumonia complicating abdominal sepsis. An independent risk factor for
      mortality.
AB  - Nosocomial pneumonia (NP) is associated with a significant mortality, 66% in a
      previous retrospective study of NP complicating intra-abdominal sepsis (IAS). We
      prospectively compared the outcome of NP complicating IAS with that of recurrent
      IAS (R-IAS) in the absence of NP. Data were collected prospectively on 300
      patients with IAS; 34 patients who presented with pneumonia were excluded from
      the analysis (44% mortality). One hundred seventy-one patients with no NP and no
      R-IAS (group 1) had a hospital mortality of 20% (34 patients); 36 without NP in
      whom R-IAS developed (group 2) had a 17% mortality (six patients); and 47 with NP
      but no R-IAS (group 3) had a 53% mortality (25 patients). Finally, 12 patients
      who had both NP and R-IAS suffered a 75% mortality (nine patients). We examined
      the relationships among the following putative risk factors and mortality: APACHE
      (acute physiology and chronic health evaluation) II score (at initial
      presentation with IAS), the need for mechanical ventilatory assistance following
      initial treatment for peritonitis, steroid requirement, generalized peritonitis
      vs abscess, and the need for surgical as opposed to percutaneous treatment. Using
      mortality as the dependent variable, group 2 vs 3 as the explanatory variable,
      and the risk factors as confounders, logistic regression analysis indicated that
      the group difference was significant after controlling for confounders. We
      conclude that NP complicating IAS is an independent risk factor associated with a
      significant mortality compared with R-IAS. These data challenge the notion that
      death in IAS is usually due to recurrent or persistent intra-abdominal infection.

PMID- 1992995
TI  - Effect of dietary fish oil on plasma thromboxane B2 and 6-keto-prostaglandin F1
      alpha levels in septic rats.
AB  - Increased mortality from sepsis is associated with high levels of thromboxane B2
      (TXB2) and 6-keto-prostaglandin F1 alpha (PGF1 alpha). Linoleic acid, an n-6
      essential fatty acid, is the usual precursor of TXB2 and PGF1 alpha, while fish
      oil is rich in n-3 essential fatty acid, the precursor of less active moieties.
      Rats were fed chow, an essential fatty acid-deficient diet, or an essential fatty
      acid-deficient diet supplemented with linoleic acid or fish oil for 2 weeks. The
      animals then underwent a sham operation or cecal ligation and puncture to induce
      sepsis. Six hours later, blood was obtained for analysis. The chow and linoleic
      acid diets produced significant (twofold to fivefold) increases in levels of both
      TXB2 and PGF1 alpha after sepsis. The essential fatty acid-deficient diet and
      fish oil diet protected against increases in levels of TXB2 or PGF1 alpha during
      sepsis. Dietary restriction of linoleic acid or fish oil supplementation may play
      an important role in altering the inflammatory mediator response to sepsis.

PMID- 1992996
TI  - Increased gut permeability following burn trauma.
AB  - Twenty female Hartley guinea pigs, weighing 350 to 400 g, were given a 30% full
      thickness burn injury. Gastrointestinal permeability was assessed before burn and
      on postburn days 1 through 3, 7, and 14 by administering 5 mL of an isotonic
      mixture of 8% lactulose and 1.15% L-rhamnose by gavage and measuring the urinary
      excretion for the next 7 hours. In normal guinea pigs, lactulose (molecular
      weight, 342d) is mostly absorbed by the paracellular route, whereas L-rhamnose
      (molecular weight, 164 d) is mostly absorbed by the transcellular route. Gut
      permeability to L-rhamnose did not increase after burn injury (211 micrograms
      before burn vs 230, 260, 180, 238, and 221 micrograms on days 1, 2, 3, 7, and 14,
      respectively, after burn). By contrast, gut permeability to lactulose increased
      significantly and was greatest in the first 48 hours after burn injury (60
      micrograms before burn vs 380, 354, 203, 364, and 279 micrograms on days 1, 2, 3,
      7, and 14, respectively, after burn). Gut permeability to low-molecular-weight
      compounds increases immediately after burn trauma, and this may be by a
      paracellular rather than transcellular mechanism.

PMID- 1992997
TI  - Hepatic extraction of indocyanine green is depressed early in sepsis despite
      increased hepatic blood flow and cardiac output.
AB  - Although active hepatocellular function is depressed during sepsis, it is not
      known whether this occurs in the very early stages of sepsis and whether it is
      due to depressed cardiac output or hepatic blood flow. To study this, rats were
      subjected to sepsis by cecal ligation and puncture and hepatocellular function
      was determined at various intervals thereafter by assessing the ability of the
      liver to clear different doses of indocyanine green. The indocyanine green
      concentration was continuously measured in vivo with a fiberoptic catheter and an
      in vivo hemoreflectometer. Maximal velocity and kinetic constant of the clearance
      of indocyanine green, hepatic blood flow, and cardiac output were determined in
      experimental and sham-operated rats. The results demonstrate that hepatic blood
      flow and cardiac output increased 2 to 10 hours after cecal ligation and
      puncture, while hepatocellular function (maximum velocity and kinetic constant)
      was decreased even 2 hours following cecal ligation and puncture. No linear
      correlation between hepatocellular function and hepatic blood flow or cardiac
      output was found under such conditions. The extremely early depression in active
      hepatocellular function, despite the increased hepatic blood flow and cardiac
      output, may form the basis for cellular dysfunctions leading to multiple organ
      failure during sepsis.

PMID- 1992998
TI  - Effects of high-dose IgG on survival of surgical patients with sepsis scores of
      20 or greater.
AB  - Sixty-two consecutive septic surgical patients receiving standard multimodal
      intensive care unit treatment who developed a sepsis score of 20 or greater (day
      0) were randomized to receive 0.4 g/kg of either intravenous IgG (29 patients) or
      human albumin (controls; 33 patients), repeated on days +1 and +5, in a
      prospective, double-blind, multicenter study. The two groups were similar in age,
      initial sepsis scores, and acute physiology and chronic health evaluation II
      score. A significantly lower mortality was recorded in the IgG-treated group
      (38%) than in controls (67%). Septic shock was the cause of death in 7% of IgG
      treated patients and in 33% of controls. The results of this study indicate that
      high-dose IgG improves survival and decreases death from septic shock in surgical
      patients with a sepsis score of 20 or greater.

PMID- 1993000
TI  - Macrophage antigen presentation and interleukin 1 production after cecal ligation
      and puncture in C3H/HeN and C3H/HeJ mice.
AB  - Following cecal ligation and puncture with a 25-gauge needle, endotoxin-sensitive
      C3H/HeN mice have a 45% mortality compared with no mortality in endotoxin
      resistant C2H/HeJ mice. Macrophage production of interleukin 1 and antigen
      presentation were studied in these two strains of mice following cecal ligation
      and puncture at 2, 4, 8, 16, and 24 hours and at 2, 4, 6, and 8 days. Splenic
      macrophages were cultured with a T-helper cell clone (D10.G4.1), and antigen
      presentation and interleukin 1 production were measured by D10.G4.1
      proliferation. Macrophage antigen presentation by C2H/HeJ mice was markedly
      increased compared with that in C3H/HeN mice at all times after cecal ligation
      and puncture, most strikingly at 2 days (185m740 cpm for C3H/HeJ mice vs 30,300
      for C2H/HeN mice). Macrophage interleukin 1 production was significantly
      increased in C3H/HeJ mice vs C3H/HeN mice at all times after cecal ligation and
      puncture (except at 2 days) and was maximal at 8 days (25,000 cpm for C3H/HeJ
      mice vs 5190 for C3H/HeN mice). These data suggest that the differences in
      mortality after cecal ligation and puncture between these two strains of mice may
      relate to a supranormal response of macrophages of C3H/HeJ mice or to an
      inadequate response of macrophages of C3H/HeN mice.

PMID- 1992999
TI  - Clostridium difficile disease in a department of surgery. The significance of
      prophylactic antibiotics.
AB  - A clustering of Clostridium difficile-associated disease in a department of
      surgery prompted a program of infection control and the evaluation of
      contributing factors. Fifty patients had diarrhea and positive assays for C
      difficile cytotoxin during the study period. Twenty-one of the 36 cases that
      developed among patients admitted to the surgical services occurred on two
      adjacent general surgery wards that shared attending surgeons and house staff.
      Perioperative prophylactic antibiotics predated C difficile-associated disease in
      20 patients, 12 of whom had short courses (less than 24 hours). Symptoms were
      typically nonspecific and early diagnosis may be difficult. Incidence remained
      high, despite infection control measures, until the coincidental closure of two
      surgical wards. Clostridium difficile-associated disease is a nosocomial
      infection that can be associated with short courses of prophylactic antibiotics.
      Recommendations regarding the use of perioperative prophylaxis should recognize C
      difficile-associated disease as a significant potential complication.

PMID- 1993002
TI  - Seizures following carotid endarterectomy.

PMID- 1993001
TI  - The vagus nerve, gastric secretions, and their relationship to peptic ulcer
      disease.
AB  - Although peptic ulcer disease was known to the ancients, the process by which the
      disease was produced remained a mystery. As advances were made in medicine and
      science, so too were advances made in the understanding of digestion and
      gastrointestinal disease. The treatment of peptic ulcer disease improved as our
      understanding of the digestive process grew. The current surgical treatment for
      peptic ulcer disease follows the principals articulated by Lester R. Dragstedt,
      MD, PhD, which he based on his observations in the research laboratory. We
      present a historical perspective of the role of the vagus nerve in the control of
      gastric secretions and its relationship to peptic ulcer disease, placing
      particular emphasis on Dragstedt's contributions.

PMID- 1993003
TI  - Convergence nystagmus associated with Arnold-Chiari malformation.

PMID- 1993004
TI  - P300 brain activity in seizure patients preceding temporal lobectomy.
AB  - Event-related potentials were recorded over occipital and parietal scalp from 20
      patients suffering from intractable partial complex seizures prior to undergoing
      a temporal lobectomy. Subjects were presented with language and nonlanguage
      visual stimuli using a divided-field, "odd-ball" paradigm. Although behavioral
      performance (button-press accuracy, reaction time, and running counts) was
      comparable across all groups (although accuracy was worse for those in the left
      temporal group), patients showed tremendous variability in both the amplitude and
      latency of the P300 response. Particularly notable was the observation that more
      slow wave activity was present among the patients than among the control
      subjects, and those scheduled for a left temporal resection evinced more
      amplitude reduction than those scheduled for a right temporal resection. In
      addition, a number of patients appeared not to show a P300 response at all. These
      results are discussed in the context of the utility of using noninvasive event
      related potential measures to examine both memory impairment and the integrity of
      the neural structures that mediate memory functioning in certain patient
      populations.

PMID- 1993005
TI  - Cognition-independent neurologic symptoms in normal aging and probable
      Alzheimer's disease.
AB  - Deep tendon reflexes, plantar responses, muscle tone, and release signs were
      studied as 14 individual clinical variables and as five summary variables in 135
      aged subjects, including 27 control subjects, 20 subjects with mild cognitive
      impairment, and 88 subjects with successive stages of probable Alzheimer's
      disease. Changes in activity of elicited responses were rated on a seven-point
      scale. Results were analyzed both as prevalence and mean degree of change in
      activity. Rating on a variable combining all 14 individual variables was
      significantly higher in a group with mild cognitive impairment than in a control
      group. Subjects with an early stage of Alzheimer's disease had both higher
      prevalence of increased activity and increased mean scores of deep tendon
      reflexes and muscle tone. They had a higher prevalence of increased activity on a
      variable combining three release signs. Patients with a late stage of Alzheimer's
      disease had significantly increased prevalence and mean scores of muscle tone and
      grasping and sucking reflexes compared with control subjects and patients with
      the early stage of Alzheimer's disease.

PMID- 1993006
TI  - Age at onset of Alzheimer's disease. Relation to language dysfunction.
AB  - A later age at onset of Alzheimer's disease (AD) was found to be related to
      diminished language performance in 86 patients with probable AD. A hierarchical
      linear model was constructed to assess effects of age at onset and disease
      duration on the performance of patients with AD on four language tasks (naming,
      reading, auditory comprehension, and writing to dictation) after controlling for
      disease severity. Results of univariate analysis, in which the dependent variable
      was the averaged language task performances, revealed a significant effect for
      age at onset of AD, but not for disease duration. To assess the possibility that
      the relationship between the age at onset of AD and language performance reflects
      effects of normal aging, the language tasks were given to 33 normal subjects of
      similar ages who scored perfectly on dementia severity measures. A convincing
      relationship was not found between test score and age.

PMID- 1993007
TI  - Anatomic, metabolic, neuropsychological, and molecular genetic studies of three
      pairs of identical twins discordant for dementia of the Alzheimer's type.
AB  - Three pairs of twins, each with proved monozygosity, were shown to be discordant
      for dementia of the Alzheimer's type and to have remained discordant for periods
      of 8 to 11 years. Dementia of the Alzheimer's type was demonstrated by history;
      serial clinical examinations; serial measurements of cerebral glucose utilization
      using positron emission tomography and of cerebral ventricular volumes and of
      rates of change of volumes using quantitative computed tomography; and by serial
      neuropsychological tests. The results of each of these measures showed no
      evidence of clinical abnormality in any unaffected twin. DNA markers from the
      proximal long arm of chromosome 21 did not distinguish between the affected and
      the unaffected member of any pair of identical twins. Family pedigrees were
      negative for Alzheimer's disease. The results suggest that environmental or other
      nongenetic factors contribute to Alzheimer's disease in discordant monozygotic
      twins, or that some cases arise by a postzygotic somatic mutation.

PMID- 1993008
TI  - The distribution of cerebral muscarinic acetylcholine receptors in vivo in
      patients with dementia. A controlled study with 123IQNB and single photon
      emission computed tomography.
AB  - A high-affinity muscarinic receptor antagonist, 123IQNB (3-quinuclidinyl-4
      iodobenzilate labeled with iodine 123), was used with single photon emission
      computed tomography to image muscarinic acetylcholine receptors in 14 patients
      with dementia and in 11 healthy controls. High-resolution single photon emission
      computed tomographic scanning was performed 21 hours after the intravenous
      administration of approximately 5 mCi of IQNB. In normal subjects, the images of
      retained ligand showed a consistent regional pattern that correlated with
      postmortem studies of the relative distribution of muscarinic receptors in the
      normal human brain, having high radioactivity counts in the basal ganglia,
      occipital cortex, and insular cortex, low counts in the thalamus, and virtually
      no counts in the cerebellum. Eight of 12 patients with a clinical diagnosis of
      Alzheimer's disease had obvious focal cortical defects in either frontal or
      posterior temporal cortex. Both patients with a clinical diagnosis of Pick's
      disease had obvious frontal and anterior temporal defects. A region of interest
      statistical analysis of relative regional activity revealed a significant
      reduction bilaterally in the posterior temporal cortex of the patients with
      Alzheimer's disease compared with controls. This study demonstrates the
      practicability of acetylcholine receptor imaging with 123IQNB and single photon
      emission computed tomography. The data suggest that focal abnormalities in
      muscarinic binding in vivo may characterize some patients with Alzheimer's
      disease and Pick's disease, but further studies are needed to address questions
      about partial volume artifacts and receptor quantification.

PMID- 1993009
TI  - Widespread functional effects of discrete thalamic infarction.
AB  - In order to investigate functional effects of various thalamic structures on
      metabolism in remote, morphologically intact cerebral regions, we used positron
      emission tomography of (18F)-2-fluoro-2-deoxy-D-glucose to study regional
      cerebral metabolic rates of glucose (rCMRGlu) in 11 patients with chronic
      unilateral or bilateral infarcts strictly confined to the thalamus. Patients were
      grouped according to computed tomographic scans showing anterior (three), medial
      (four), or posterior (four) lesions. Compared with a matched group of 11 healthy
      subjects (hemispheric CMRGlu 35.2 +/- 3.49 mumol/100 g per minute), glucose
      metabolism was significantly lower in the hemisphere ipsilateral to the
      infarction (31.2 +/- 2.97 mumol/100 g per minute). Patients with bilateral
      infarcts had lower hemispheric CMRGlu (29.9 +/- 2.74 mumol/100 g per minute) than
      those with unilateral lesions (32.2 +/- 2.97 mumol/100 g per minute). Depending
      on infarct location within the thalamus, there was differential depression of
      rCMRGlu, with the largest effects on frontal and occipital areas in medial
      infarctions. Except for ipsilateral thalamic deactivation, metabolic patterns
      with anterior thalamic infarcts were close to normal, while posterior infarcts
      mostly depressed rCMRGlu in the visual and in the inferior limbic cortex.
      Cerebellar metabolic rates were within normal limits in most cases. These
      patterns of regional cerebral deactivation may be related to categories of
      thalamic projections--intrathalamic, to limbic system and basal ganglia, diffuse
      to most cortical areas, and specific to defined neocortical areas. Even small
      brain lesions may have widespread functional sequelae, potentially demonstrable
      by positron emission tomography.

PMID- 1993010
TI  - Spectral analysis of heart rate in diabetic autonomic neuropathy. A comparison
      with standard tests of autonomic function.
AB  - Power spectral analysis of the heart rate was compared with standard tests of
      autonomic function performed on 15 insulin-dependent diabetic patients with
      symptoms of autonomic dysfunction. The high-frequency power, low-frequency power,
      and total power of the heart rate power spectrum measured in the supine position-
      possible measures of parasympathetic nervous system function--were significant
      predictors of the expiratory-inspiratory ratio, the beat-to-beat heart rate
      difference on deep respiration, the standard deviation of the resting heart rate,
      the 30:15 ratio, and the Valsalva ratio. The change in low-frequency power on
      moving from the supine to upright position, a possible measure of sympathetic
      nervous system function, was a modest predictor of the systolic and diastolic
      blood pressure fall in response to postural change, but a poor predictor of the
      blood pressure response to isometric exercise and a cold stimulus. This study
      supports the role of heart rate power spectral analysis as a clinical test of
      autonomic function in patients with known or suspected autonomic failure.

PMID- 1993011
TI  - Treatment of multiple sclerosis with hyperbaric oxygen. Results of a national
      registry.
AB  - Three hundred twelve patients were entered into a long-term study of effects of
      hyperbaric oxygen on multiple sclerosis. The protocol called for an initial 20
      treatments in either the monoplace or multiplace chamber on a daily basis
      followed by monthly booster treatments for 2 years. One hundred seventy
      neurologists and 22 institutions provided data for this study. There was no
      control group, but the study was based on Schumacher's postulation that a
      scientifically valid study to test the efficacy of a new therapy was possible by
      choosing patients who were definitively diagnosed with multiple sclerosis and
      following them up for 2 years after the imposed treatment. If the overwhelming
      majority of the subjects failed to get worse over the 2-year observation period,
      the efficacy of the treatment would be manifest. The expanded Kurtzke Disability
      Status Scale (EDSS) was used to assess the severity of the disease state. The
      dropout rate was high with only 76% (237 of 312 patients) finishing the initial
      20 treatments. Twenty-two percent (69 of 312) finished 1 year of booster therapy,
      and 9% (28 of 312) completed 2 years of monthly boosters. The mean deterioration
      on the Kurtzke EDSS score was 0.93 or almost a full step from the beginning of
      treatment until the last evaluation. There was no difference in outcome between
      those who had the shortest and longest periods of time between onset of symptoms
      and hyperbaric oxygen treatment. Treatment pressure made no difference in
      outcome. Changes in the Kurtzke EDSS score bore no relationship to the use of
      booster treatment. Patients who were reasonably well off at the onset of
      treatment with initial Kurtzke EDSS scores of 1 or 2 (n = 21) deteriorated by an
      average of 1.7 Kurtzke points. Those patients whose initial Kurtzke EDSS scores
      were greater than 2 (n = 164) deteriorated on an average of 0.82 points. Of
      interest was that 19.5% (39 of 200) of the patients reported a temporary
      improvement in bladder function, but improvement was maintained in only 11
      patients (5.5%) at 2-year follow-up. Fifteen patients (7.5%) indicated long-term
      worsening. There was no significant change in the working status of the patients
      following hyperbaric oxygen treatment. Although this study treated the patients
      in accordance with protocols reported to produce a benefit in multiple sclerosis,
      we were unable to substantiate any useful long-term effect of hyperbaric oxygen
      therapy.

PMID- 1993012
TI  - Alterations in brain phosphate metabolite concentrations in patients with human
      immunodeficiency virus infection.
AB  - Human immunodeficiency virus (HIV)-infected individuals often demonstrate
      neuropsychiatric impairment; however, it is unclear how brain metabolism may be
      altered in such patients. We used in vivo phosphorus 31 magnetic resonance
      spectroscopy to noninvasively assess brain energy and phospholipid metabolism by
      measuring brain concentrations of adenosine triphosphate (ATP), phosphocreatine
      (PCr), and inorganic phosphate (Pi), as well as phospholipid compounds and
      intracellular pH. In study 1, 17 HIV-seropositive men with varying degrees of
      neuropsychiatric impairment and six control subjects were studied. Localized
      spectra were obtained from a heterogeneous 5 x 5 x 5-cm volume of interest (VOI).
      Patients with HIV infection had a significantly lower ATP/Pi ratio and a trend
      for a lower PCr/Pi ratio than did the control group. In addition, the ATP/Pi and
      PCr/Pi ratios were both significantly negatively correlated with overall severity
      of neuropsychiatric impairment. In study 2, three HIV-seropositive men with
      neuropsychiatric impairment were compared with 11 HIV-seronegative men. Localized
      phosphorus 31 magnetic resonance spectra were obtained from two relatively
      homogeneous VOIs: (1) a predominantly white matter VOI, and (2) a predominantly
      subcortical gray matter VOI. The three HIV-infected patients demonstrated
      significantly decreased ATP and PCr concentrations in the white matter VOI. These
      results suggest that HIV infection of the brain may impair brain cellular
      oxidative metabolism and that the degree of metabolic compromise may be related
      to the severity of neuropsychiatric impairment.

PMID- 1993013
TI  - Posttraumatic torticollis.
AB  - We report six cases of torticollis precipitated by neck trauma. The dystonia
      began 1 to 4 days after the trauma and differed clinically from idiopathic
      torticollis by marked limitation of range of motion, lack of improvement after
      sleep ("honeymoon period"), and absence of geste antagonistique. Worsening with
      action was not present; nor was there improvement with support as seen with
      idiopathic torticollis. Onset of pain immediately after the trauma and marked
      spasms of the paracervical muscles were other predominant features.
      Anticholinergic therapy was without benefit; however, some improvement occurred
      with botulinum toxin injection. It is concluded that torticollis can be caused by
      peripheral trauma and that it has unique clinical characteristics.

PMID- 1993014
TI  - Chemotherapy for oligodendroglioma. Progress report.

PMID- 1993015
TI  - Anaplastic oligodendrogliomas.

PMID- 1993016
TI  - An early description of slowly progressive aphasia.
AB  - Slowly progressive aphasia without generalized dementia has become an important
      issue of present-day neuropsychological research. Historically, credit for the
      first description is usually given to Pick. Another German-speaking author who
      has published a vivid description of a pertinent cases is Pick's contemporary,
      Max Rosenfeld. This author has also observed a patient with slowly progressive
      spatial disorientation and visual recognition deficit, and he has discussed these
      patients in a remarkably modern way in the context of partial atrophy of the
      brain.

PMID- 1993017
TI  - Frontal impairment and hypoperfusion in neuroacanthocytosis.
AB  - Cerebral blood flow tomography, by xenon 133 inhalation or HMPAO (99mTc-d, l
      hexamethyl-propylene amine oxime) technetium Tc 99m injection, revealed a severe
      hypoperfusion in both frontal lobes of a 40-year-old woman with confirmed
      neuroacanthocytosis. This finding occurred in conjunction with neuropsychological
      deficits consistent with selective frontal lobe dysfunction. This observation is
      the first documentation of this type of dementia in neuroacanthocytosis.

PMID- 1993018
TI  - A new lubricant (carboxymethylcellulose) for contact lens examination.

PMID- 1993019
TI  - Hazards of unit dose artificial tears.

PMID- 1993020
TI  - Anterior segment ischemia following vertical muscle transposition and botulinum
      toxin injection.

PMID- 1993021
TI  - Retinitis pigmentosa misdiagnosed as complicated migraine.

PMID- 1993022
TI  - Endophthalmitis therapy: changing antibiotic sensitivity patterns and current
      therapeutic recommendations.

PMID- 1993023
TI  - Chronic Alternaria alternata endophthalmitis following intraocular lens
      implantation.

PMID- 1993024
TI  - Eyelid lymphedema.

PMID- 1993025
TI  - Spontaneous retinal capillary reperfusion in a systemic illness.

PMID- 1993026
TI  - Drug company gifts to physicians to be curbed.

PMID- 1993027
TI  - Who develops cataracts?

PMID- 1993028
TI  - Optic nerve head and nerve fiber layer in Alzheimer's disease.
AB  - We compared (1) the differences in the retinal nerve fiber layer between 26
      patients with Alzheimer's disease and 30 age- and race-matched normal controls
      with use of blue-light high-resolution photography, (2) the differences in disc
      pallor between 30 patients with Alzheimer's disease and 32 controls with use of a
      boundary-tracking program and fundus photographs, and (3) the topographic disc
      variables between 26 patients with Alzheimer's disease and 36 controls with use
      of an optic nerve head analyzer. A higher proportion of patients with Alzheimer's
      disease had detectable nerve fiber damage as seen by red-free photography
      compared with controls. Although the pallor area-to-disc area ratio was not
      significantly different between patients with Alzheimer's disease and controls,
      the patients with higher pallor area-to-disc area ratios had higher Alzheimer's
      Disease Assessment Scale (ADAS) scores and longer durations of disease. Patients
      had an increased cup-to-disc ratio and cup volume and decreased disc rim area
      compared with controls. These variables also correlated significantly with ADAS
      scores and the duration of disease. The correlation among the optic nerve head
      changes and the ADAS scores in patients with Alzheimer's disease suggests a
      potential role for optic nerve head analysis in monitoring the progression of
      Alzheimer's disease and in assessing the effectiveness of any treatments
      developed.

PMID- 1993029
TI  - Falls in elderly patients with glaucoma.
AB  - We analyzed the determinants of serious falls among 489 ambulatory elders aged 65
      years and older who received a comprehensive examination at a glaucoma
      consultation service. For the previous year, at least one fall requiring medical
      attention or restricted activity was reported by 9.6% (95% confidence interval
      [CI], 7.0% to 12.2%) of participants. Using logistic regression to adjust for
      potential confounding variables, the greatest single risk factor for falls was
      the use of nonmiotic topical eye medications (odds ratio [OR], 5.4; 95% Cl, 1.8
      to 16.4). Additional risk factors for falls were female sex (OR, 2.3; 95% Cl, 1.1
      to 4.7) and use of cardiac medications (OR, 2.5; 95% Cl, 1.1 to 5.6). Three other
      characteristics were also associated with the risk of falls: use of miotic eye
      medications (OR, 3.2; 95% Cl, 1.0 to 10.1); visual field impairment of 40% or
      greater (OR, 3.0; 95% Cl, 0.94 to 9.8); and use of sedatives (OR, 2.4; 95% Cl,
      0.89 to 6.7). These findings suggest that ocular and systemic medications are the
      major predictors of falls even in this elderly population seeking ophthalmologic
      care for glaucoma. Medications appear to pose a greater risk for falls than even
      major visual impairment.

PMID- 1993030
TI  - The nature of head postures in congenital nystagmus.
AB  - We investigated the factors that determine the nature and extent of abnormal head
      postures in patients with congenital nystagmus. The head positions and eye
      movements of 16 patients were monitored while they adopted a variety of gaze
      positions. Five patients displayed a single head posture and four displayed
      multiple head postures. Six of the nine head postures matched the minimum
      intensity zone. The extent of the head posture was also found to be dictated by
      the velocity distribution of the slow phase, the nystagmus beat direction, and
      the neutral zone. Our results suggest that the surgical management of a head
      posture should not always be based only on the relocation of the minimum
      intensity zone to the primary gaze position.

PMID- 1993031
TI  - Large rectus muscle recessions for the treatment of congenital nystagmus.
AB  - Retroequatorial recessions of the horizontal rectus muscles 10 to 12 mm behind
      their insertions reduced the amplitude of manifest congenital nystagmus in three
      patients. Modest improvement of visual acuity occurred in two patients. In a
      third patient with periodic alternating nystagmus, a compensatory head turn was
      eliminated by shifting the neutral zone of the nystagmus to the primary position
      of gaze. In spite of large recessions of the muscle insertions, none of the
      patients had a functionally significant postoperative limitation of ocular
      motility.

PMID- 1993033
TI  - Visual evoked potentials and visual prognosis following perinatal asphyxia.
AB  - Twenty-five children born at term with perinatal asphyxia were studied at age 2.5
      to 4.5 years to evaluate visual function and to determine the prognostic value of
      postnatal assessments of visual outcome. Postnatal assessments included several
      visual evoked potentials and electroretinograms in the first week of life. Follow
      up assessments included flash and pattern visual evoked potentials, visual evoked
      potential threshold measurements, and clinical eye examinations. Nineteen
      children had normal visual function, three were visually impaired, and three
      remained blind. A strong association was found between normal, abnormal, or
      absent visual evoked potentials in the early postnatal period and long-term
      visual outcome (P less than .0001). Other perinatal indicators of asphyxia,
      including neurologic status, Apgar scores, and arterial pH values, were poor
      predictors of visual outcome. The risk of visual impairment was limited to those
      survivors with neurodevelopmental deficits.

PMID- 1993032
TI  - Microaerosol formation in noncontact 'air-puff' tonometry.
AB  - Attention has been directed recently to appropriate methods for sterilizing
      tonometers to inactivate the human immunodeficiency virus and other viruses that
      have been found in tears. Noncontact tonometry, utilizing a brief pulse of
      pressurized air, is an alternative that avoids the need for sterilization
      procedures. We used a camera and flash electrically coupled to an American
      Optical Non-Contact II tonometer (Cambridge Instruments Inc, Cambridge, Mass) or
      a Keeler Pulsair tonometer (Keeler Instruments Inc, Broomall, Pa) to photograph
      the corneal profile during tonometry. Most eyes revealed some degree of tear film
      dehiscence and microaerosol formation. While tears have not been implicated as a
      source of human immunodeficiency virus infection, the ease with which droplets,
      potentially contaminated with human immunodeficiency virus and other viruses, are
      dispersed is disturbing. "Air-puff" tonometry may not be aseptic as previously
      presumed.

PMID- 1993034
TI  - Evolving ophthalmology-optometry relationships.

PMID- 1993035
TI  - Lipomatous hamartoma of the orbit.
AB  - Proliferations of mature adipose tissue, while common in retroperitoneal and
      subcutaneous sites, rarely occur in the orbit. We describe the clinical,
      radiographic, and histopathologic findings of a nonencapsulated lipomatous tissue
      overgrowth of the right orbit in a 35-year-old man. The mass had caused proptosis
      since childhood and was apparently present since birth. Due to the age at onset,
      the histologic similarity to normal orbital fat, and the lack of encapsulation or
      choristomatous elements, we propose the term lipomatous hamartoma for this
      entity.

PMID- 1993036
TI  - The Lens Opacities Case-Control Study. Risk factors for cataract.
AB  - The Lens Opacities Case-Control Study evaluated risk factors for age-related
      nuclear, cortical, posterior subcapsular, and mixed cataracts. The 1380
      participants were ophthalmology outpatients, aged 40 to 79 years, classified into
      the following groups: posterior subcapsular only, 72 patients; nuclear only, 137
      patients; cortical only, 290 patients; mixed cataract, 446 patients; and
      controls, 435 patients. In polychotomous logistic regression analyses, low
      education increased risk (odds ratio [OR] = 1.46) and regular use of multivitamin
      supplements decreased risk (OR = 0.63) for all cataract types. Dietary intake of
      riboflavin, vitamins C, E, and carotene, which have antioxidant potential, was
      protective for cortical, nuclear, and mixed cataract; intake of niacin, thiamine,
      and iron also decreased risk. Similar results were found in analyses that
      combined the antioxidant vitamins (OR = 0.40) or considered the individual
      nutrients (OR = 0.48 to 0.56). Diabetes increased risk of posterior subcapsular,
      cortical, and mixed cataracts (OR = 1.56). Oral steroid therapy increased
      posterior subcapsular cataract risk (OR = 5.83). Females (OR = 1.51) and
      nonwhites (OR = 2.03) were at increased risk only for cortical cataract. Risk
      factors for nuclear cataract were a nonprofessional occupation (OR = 1.96),
      current smoking (OR = 1.68), body mass index (OR = 0.76), and occupational
      exposure to sunlight (OR = 0.61). Gout medications (OR = 2.48), family history
      (OR = 1.52), and use of eyeglasses by age 20 years, which is an indicator of
      myopia (OR = 1.44), increased risk of mixed cataract. The results support a role
      for the nutritional, medical, personal, and other factors in cataractogenesis.
      The potentially modifiable factors suggested by this study merit further
      evaluation.

PMID- 1993037
TI  - Low-dose aspirin and risks of cataract in a randomized trial of US physicians.
AB  - Observational studies have raised the question of a possible benefit of aspirin
      on the development of cataract. The Physicians' Health Study, a randomized double
      masked placebo-controlled trial among 22,071 male physicians, aged 40 to 84
      years, provided the opportunity to collect information about whether low-dose
      aspirin therapy (325 mg on alternate days) affects the development or extraction
      of cataract. There were 173 age-related cataracts among those physicians assigned
      to aspirin therapy and 180 among those given placebo (relative risk, 0.95; 95%
      confidence interval, 0.74 to 1.22). Cataract extractions were less frequent in
      the aspirin than in the placebo group, but this difference was not statistically
      significant (relative risk, 0.80; 95% confidence interval, 0.56 to 1.15). Among
      younger men (aged 40 to 59 years), the relative risks were 0.62 (95% confidence
      interval, 0.40 to 0.94) for cataract development and 0.67 (95% confidence
      interval, 0.38 to 1.31) for cataract extraction. These randomized trial data tend
      to exclude any large benefit of aspirin. While the overall findings concerning
      cataract development seem to be null, the data on extraction of age-related
      cataract, while not statistically significant, cannot exclude a possible small to
      moderate benefit of alternate-day aspirin therapy on the extraction of age
      related cataract.

PMID- 1993038
TI  - Effects of antiflammins on endotoxin-induced uveitis in rats.
AB  - Antiflammins are phospholipase A2-inhibitory, anti-inflammatory, synthetic
      oligopeptides derived from the region of the highest amino-acid sequence
      similarity between uteroglobin and lipocortin I. Endotoxin-induced uveitis is a
      model for anterior uveitis of the eye, which has been suggested to be induced
      through phospholipase A2 activation. In a preliminary report we demonstrated that
      topical administration of antiflammins could inhibit endotoxin-induced uveitis in
      rats. In this study, the anti-inflammatory effects of antiflammins were compared
      with those of corticosteroids on endotoxin-induced uveitis as measured by
      phospholipase A2 enzyme activity, inflammatory cell counts in the aqueous humor,
      and histopathologic features. Antiflammins are as effective as corticosteroids in
      their ability to suppress endotoxin-induced uveitis.

PMID- 1993039
TI  - Hydatid cyst of the orbit.

PMID- 1993040
TI  - Hemorrhagic lymphangiectasia of the conjunctiva.

PMID- 1993041
TI  - Autogenous fascial grafts for exposed retinal buckles.
AB  - Three patients with exposed scleral buckling elements received autogenous fascial
      grafts as an alternative to buckle removal. All three patients had successful
      coverage of their scleral buckles. There were no redetachments or infections. One
      patient had a postoperative ptosis that required repair. Autogenous fascial
      grafts are useful procedures in patients with exposed retinal buckles who have a
      significant risk of retinal redetachment with buckle removal.

PMID- 1993042
TI  - A quantifiable phenotype of viral propagation.
AB  - A system has been identified where a virus, replicating continuously on its host,
      displays a distinct and quantifiable phenotype, and thereby continuously reports
      on the state of the virus-host relationship. When bacteriophage T7 is plated out
      with its host, Escherichia coli, it establishes a constant-velocity infection
      wave, which is driven by an autocatalytic reaction-diffusion mechanism. The
      velocity--which is easily measured--continuously reflects the infection
      environment. The simplicity of the system extends to the investigator an
      unprecedented ability to monitor and control a viral infection process.

PMID- 1993043
TI  - Tetrahymena 14-nm filament-forming protein has citrate synthase activity.
AB  - The Tetrahymena 14-nm filament-forming protein (49K protein) is a structural
      protein involved in oral morphogenesis and in pronuclear behavior during
      conjugation. Cloning the 49K protein gene from a Tetrahymena thermophila cDNA
      library, we found that its primary structure exhibits a high sequence identity
      (51.5%) with porcine heart citrate synthase and retains functional domains. The
      49K protein actually possesses citrate synthase activity, and is detected in
      mitochondria. These results suggest that the 49K protein has dual functions as
      both a respiratory enzyme and a structural protein in the cytoskeleton.

PMID- 1993044
TI  - The structure of the brain-specific rat aldolase C gene and its regional
      expression.
AB  - The rat aldolase C gene was isolated from a rat genomic DNA library. This gene
      comprises 9 exons and spans 3590 base pairs. A single copy of the gene occurs per
      haploid rat genome. The initiation of transcription occurs at two different
      sites. The cellular localization of aldolase C mRNA was determined in the central
      nervous system along with aldolase A mRNA by in situ hybridization. The result
      indicates the predominant expression of this gene in Purkinje cells of the
      cerebellar cortex, where aldolase A mRNA was rather repressed.

PMID- 1993045
TI  - Synaptic and extra-synaptic distribution of histamine H1-receptors in rat and
      guinea pig brains.
AB  - Localization of histamine H1-receptors in subcellular fractions from rat and
      guinea pig brains was examined in a [3H]mepyramine binding study. Major
      [3H]mepyramine binding sites with increased specific activities [( 3H]mepyramine
      binding vs. protein amount) were recovered from P2 fractions from both rat and
      guinea pig brains by differential centrifugation. Further subfractionation of
      both rat and guinea pig P2 fractions by a discontinuous sucrose density gradient
      centrifugation showed the highest recovery of [3H]mepyramine binding with further
      increased specific activities found in synaptic plasma membrane (SPM) fractions.
      Minor [3H]mepyramine binding sites with increased specific activities were
      detected in both rat and guinea pig P3 fractions. [3H]Mepyramine binding sites in
      SPM and P3 fractions showed identical Kd values in each species. These results
      indicate that histamine H1-receptors are located not only in synaptic but also in
      extra-synaptic membranes of both rat and guinea pig brains.

PMID- 1993046
TI  - Predominance of type III over type I cell surface procollagens in rat lung
      fibroblasts.
AB  - Binding assays of 125I-labeled affinity-purified monospecific type I and III
      procollagen antibodies to fibroblasts have revealed the presence of type I and
      III procollagens on the cell surface, and that the amount of type III procollagen
      is 10 times greater than that of type I procollagen. Analyses by flow cytometry
      and fluorescent microscopy after treatment with an isothiocyanate (FITC)
      conjugated second antibody supported this finding.

PMID- 1993047
TI  - Interleukin-1 induced gene expression of neutrophil activating protein
      (interleukin-8) and monocyte chemotactic peptide in human synovial cells.
AB  - We report here that human synovial cells stimulated by interleukin-1 alpha and
      interleukin-1 beta express mRNA for both IL-8 (neutrophil chemotactic peptide)
      and monocyte chemotactic protein. IL-1 stimulated synovial cells from both
      osteoarthritis and rheumatoid arthritis patients exhibited similar mRNA
      expression of interleukin-8 and monocyte chemotactic protein. A capacity to
      produce factors selectively chemotactic for neutrophils, lymphocytes and
      monocytes provides a mechanism whereby synovial cells can facilitate inflammatory
      arthritis.

PMID- 1993048
TI  - Molecular cloning and sequencing of the epidermal cell differentiation inhibitor
      gene from Staphylococcus aureus.
AB  - We recently purified to homogeneity a protein inhibiting differentiation of
      cultured keratinocytes from extracellular products of Staphylococcus aureus, and
      named it epidermal cell differentiation inhibitor (EDIN). In the present study,
      we isolated and sequenced the structural gene coding for EDIN from Staphylococcus
      aureus E-1 using oligonucleotide probes on the basis of the partial amino acid
      sequence of the purified EDIN. DNA sequencing of the cloned DNA revealed an open
      reading frame encoding 247 amino acids as a precursor of EDIN, which included an
      NH2-terminal signal sequence of 35 amino acid residues. Processing of this
      precursor produces a mature EDIN protein composed of 212 amino acids with a
      calculated Mr of 23,782. The EDIN shared 35% amino acid homology with the ADP
      ribosyltransferase C3 of Clostridium botulinum. These results with biological
      properties of EDIN described previously indicate that EDIN is a novel protein.

PMID- 1993049
TI  - Transformed rodent cells exhibit increased resistance to the carboxylic
      ionophores monensin and nigericin.
AB  - Rodent fibroblasts transformed with the Kirsten and Moloney murine sarcoma
      viruses exhibit increased resistance to the growth inhibitory and cytotoxic
      action of the carboxylic Na+/H+ ionophore, monensin. The inhibitory effect of
      monensin on cell proliferation requires exposure for periods longer than 24
      hours. The virus-transformed cells also exhibit increased resistance to the K+/H+
      ionophore, nigericin. Since monensin is known to have significant effects upon
      the function and activity of the Golgi apparatus and the intracellular
      trafficking and processing of endocytosed as well as cell-derived materials, the
      results suggest that alterations in the activities of the organelles and pathways
      involved with intracellular protein trafficking and processing likely make an
      important contribution to the biological and cellular properties of transformed
      cells.

PMID- 1993050
TI  - Evidence for an inactive plasma membrane-associated precursor of active
      cytoplasmic ornithine decarboxylase in developing embryos of Musca domestica.
AB  - During embryonic development of Musca domestica inactive ornithine decarboxylase
      protein appears in the embryos at 6 h postoviposition, increases in concentration
      and reaches a maximum level at 9 h postoviposition. The inactive enzyme is
      associated with the plasma membrane and appears to be the precursor for active
      ornithine decarboxylase, which is associated with the cytosolic fraction just
      prior to hatching. Both ornithine decarboxylase protein and enzymatic activity
      disappear during the early larval stage of this insect.

PMID- 1993052
TI  - Purification of a novel 55 kDa HeLa cell nuclear DNA-binding protein.
AB  - A novel 55 kDa DNA-binding protein (p55) was purified from HeLa cell nuclear
      extracts to apparent homogeneity by conventional chromatography coupled with DNA
      affinity chromatography. The DNA-binding activity of p55, followed by band
      mobility shift and Southwestern assays, was enriched 800-fold. This relatively
      abundant protein was shown to bind nonspecifically to DNA. When added to nuclear
      extracts, p55 enhanced 2-fold the in vitro transcription of CAT reporter gene
      driven by the SV40 promoter. The sequence of the N-terminal 20 amino acid
      residues of purified p55 was determined as APSTPLLTV(P)G(S)EGLYMVNG, homologies
      could be found when compared to protein sequences available in all databanks.

PMID- 1993051
TI  - Thermal stability of hemoglobin crosslinked in the T-state by bis(3,5
      dibromosalicyl) fumarate.
AB  - Bis(3,5-dibromosalicyl) fumarate was used to crosslink oxyhemoglobin between Lys
      82 beta 1 and Lys 82 beta 2 (Walder, J. A., et al. (1979) Biochemistry 18, 4265)
      and deoxyhemoglobin between Lys 99 alpha 1 and Lys 99 alpha 2 (Chatterjee R.Y.,
      et al. (1986) J. Biol. Chem. 261, 9929). Thermal denaturations demonstrated that
      alpha crosslinked hemoglobin (alpha 99XLHb A) has the same stability as the beta
      crosslinked one (beta 82XLHb A). Both alpha and beta crosslinked methemoglobins
      have a denaturation temperature in 0.9 M guanidine of 57 degrees C compared to 41
      degrees C of Hb A. The second product from the T-state crosslinking reaction was
      found to be crosslinked between the beta chains by chain separation and amino
      acid analysis. The possible positions for this crosslink are limited to the
      bisphosphoglycerate binding site in the three-dimensional structure. Its
      stability is comparable to that of the alpha 99XLHb A or beta 82XLHb A. These
      modified hemoglobins are potential blood substitutes.

PMID- 1993053
TI  - Immunocytochemical localization of ubiquitin-activating enzyme in the cell
      nucleus.
AB  - Ubiquitin-activating enzyme, "E1", is the first enzyme in the pathway leading to
      formation of ubiquitin-protein conjugates. We present immunocytochemical evidence
      that Ubiquitin-activating enzyme is concentrated in the cell nucleus. This
      finding points to the nucleus as the major site of action of this enzyme. Since
      ubiquitin itself is not similarly compartmentalized, this result suggests a high
      level of ubiquitin conjugate formation in the nucleus with a rapid turnover of
      ubiquitin conjugates.

PMID- 1993054
TI  - Beta-amyloid from Alzheimer disease brains inhibits sprouting and survival of
      sympathetic neurons.
AB  - The significance of the amyloid plaque core proteins (APCP) in Alzheimer's
      disease (AD) and its consequences for neuronal survival have been controversial.
      To address this problem we purified the APCP and beta A obtained from brains with
      AD, and assessed their biological effects in tissue culture. APCP and beta A
      caused severe toxicity to chick and rat sympathetic and sensory neurons whose
      survival is dependent upon NGF. This toxicity was dose dependent and reversible
      at low doses. APCP and beta A prevented sprouting of neurites in freshly plated
      neurons. In established cultures addition of these molecules caused vacuolation
      and fragmentation of neurites and disintegration of neuronal soma. We suggest
      that the deposition of APCP in AD may be partly responsible for the destruction
      of the neuritic arbor, thereby contributing to the formation of the neuritic
      plaque and to neuronal death.

PMID- 1993055
TI  - Inactivation of human placenta glutathione S-transferase by SH/SS exchange
      reaction with biological disulfides.
AB  - The oxidized glutathione inhibited the activity of glutathione S-transferase
      purified from human placenta just through competitive inhibition. On the other
      hand, cystine and cystamine inactivated the activity by pseudo first-order in low
      concentrations, accompanying the stoichiometric incorporation of the
      radioactivity of [14C]-cystine to the enzyme protein until a half mole per one
      subunit. This and the protective effect of glutathione analogues suggested that
      the SH/SS exchange reaction occurred between the disulfide and the SH group near
      the glutathione binding site of the enzyme to form a mixed disulfide.

PMID- 1993056
TI  - A motif found in propeptides and prohormones that may target them to secretory
      vesicles.
AB  - Sorting of prohormones and propeptides into secretory vesicles at the trans-Golgi
      face probably depends on a signal contained within the amino acid sequence of the
      peptide. To date no consensus sequence has been identified in prohormones or
      propeptides that might serve such a targeting function. In this report, we have
      analyzed the amino acid sequences and secondary structures of 15 prohormones and
      propeptides that have been shown experimentally to be sorted to secretory
      vesicles when the corresponding cDNA is transfected into mouse pituitary AtT20
      cells. From these analyses, we have identified a motif that is shared by all of
      these diverse propeptides and might serve as a vesicular targeting sequence. This
      motif is degenerate and consists of two or more leucines occupying one side of a
      highly amphipattic alpha helix with a serine (or rarely threonine) positioned N
      terminal to the leucines and projecting to the same side of the helix.

PMID- 1993057
TI  - The biosynthesis of endothelin-1 by human polymorphonuclear leukocytes.
AB  - Human polymorphonuclear leukocytes (PMNs) converted human big endothelin (bET; 2
      microM) to an endothelin-1 (ET-1) like contractile factor, as assessed by
      bioassay. The generation of this ET-1 like activity was rapid (minutes), time
      dependent and more pronounced in non-activated cells, suggesting a partial
      degradation by activated PMNs. Phosphoramidon (54 micrograms/ml) inhibited the
      formation of this contractile factor, whereas phenylmethylsulfonylfluoride (PMSF;
      25 micrograms/ml), pepstatin A (1 microgram/ml) or epoxysuccinyl-L-leucylamido
      (guanidino)butane (E-64; 10 micrograms/ml) did not. Incubations of activated PMNs
      with PMSF significantly potentiated the generation of ET-1 like activity and
      selectively inhibited the degradation of [125I]ET-1 by activated PMNs. These
      findings indicate that human PMNs contain and/or release neutral proteases, which
      can both rapidly produce and degrade ET-1, an observation which may have
      important (patho)physiologic implications.

PMID- 1993058
TI  - Inhibition of methylcoenzyme M methylreductase by a uridine 5'-diphospho-N
      acetylglucosamine derivative.
AB  - Uridine-5'-diphospho-N-acetylglucosamine, when oxidized with periodate to the
      corresponding aldehyde (o-UDP-GlcNAc), was a potent inhibitor of the
      methylcoenzyme M methylreductase reaction which catalyzes the reductive
      demethylation of methylcoenzyme M to methane. The oxidation product, o-UDP
      GlcNAc, appears to bind to the UDP-GlcNAc site of the enzyme and inhibits the
      reduction of methylcoenzyme M both by MRF or its active hydrolytic fragment HS
      HTP. The kinetic patterns indicate that o-UDP-GlcNAc inhibition is noncompetitive
      with HS-HTP or MRF, and the Hill coefficient indicated that there was
      cooperativity between the UDP and HS-HTP binding sites. The methylreductase
      enzyme was protected from o-UDP-GlcNAc inhibition by prior exposure to low
      concentrations of MRF. HS-HTP, at the same concentration as MRF, was not
      effective in protecting the enzyme from inhibition by o-UDP-GlcNAc.

PMID- 1993059
TI  - Salivary histatin as an inhibitor of a protease produced by the oral bacterium
      Bacteroides gingivalis.
AB  - We examined the effect of histatin 5 from human parotid saliva on various
      proteases. Histatin 5 strongly inhibited a trypsin-like protease produced by
      Bacteroides gingivalis with an IC50 value of 55 nM. Clostripain was also
      inhibited (IC50 = 800 nM). Activities of other proteases were not affected
      significantly. Because B. gingivalis is a suspected periodontal pathogen and its
      proteolytic enzymes have been considered to be associated with periodontal tissue
      destruction, it is suggested that salivary histatins play a role as a preventive
      against periodontal disease.

PMID- 1993060
TI  - Yeast proteins with reactivity to antibodies elicited against mammalian
      apolipoproteins.
AB  - Hyperimmunized rabbit anti-rat apolipoprotein antibodies showed reactivity to
      proteins in Saccharomyces cerevisiae. Antiapolipoproteins A1, B and E reacted
      with proteins in both a crude extract and a lipid enriched fraction. Protein
      reactivity was dependent on antisera dilution. Furthermore, the different
      antiapolipoproteins tested reacted with individually distinct yeast proteins,
      possibly suggesting the presence of a variety of yeast apolipoproteins with
      distinct cellular functions as is the case with mammalian apolipoproteins. The
      specificity of the antibody was directed toward the yeast protein and not a lipid
      moiety.

PMID- 1993061
TI  - Specific gangliosides increase rapidly in rat liver following partial
      hepatectomy.
AB  - Rat liver gangliosides (sialic acid containing glycosphingolipids) were analyzed
      by HPTLC and HPLC following either partial hepatectomy or sham operation.
      Analysis of whole liver gangliosides by HPTLC demonstrated that within 6 h after
      partial (68%) hepatectomy, there was a significant increase in GM1 compared to
      both sham and control animals. By 48 h, GM1 was further increased and the
      polysialylgangliosides GD1a, GD1b and GT1b had also risen significantly, whereas
      changes in GM3 were negligible. Gangliosides associated with the plasma membrane
      were increased up to 3.5-fold in regenerating liver compared to sham
      hepatectomized controls as assessed by HPLC. Although elevations in membrane
      gangliosides were associated with hepatocyte proliferation, they did not closely
      follow the growth curve. The time course of changes in ganglioside biosynthesis
      suggests differential upregulation of GM3 synthase and GD3 synthase in
      regenerating livers.

PMID- 1993062
TI  - Stimulation of macrophage growth and multinucleated cell formation in rat bone
      marrow cultures by insulin-like growth factor I.
AB  - In this study the effects of rhIGF-I on macrophage differentiation and growth
      have been studied using liquid suspension cultures of rat bone marrow cells. IGF
      I stimulated macrophage growth in a dose-dependent manner, a maximum response was
      found at a concentration of 20 ng/ml. IGF-I effects could be ascribed to
      stimulation of both postmitotic and proliferating cells. A remarkable finding was
      that IGF-I induced formation of multinucleated cells (MNC). The MNC resembled
      macrophage-like cells (AcP, NSE positive). A monoclonal antibody to rhIGF-I
      significantly inhibited IGF-stimulated macrophage growth and MNC formation. A
      specific antibody to mouse CSF-1 reduced IGF-stimulated macrophage growth in
      mouse bone marrow cultures indicating that IGF-I effects could, at least in part,
      be ascribed to endogenous production of CSF-1. These findings indicate that IGF-I
      in concert with locally induced CSF-1 can influence the differentiation and
      growth of bone marrow-derived macrophages.

PMID- 1993063
TI  - Deoxycytidine is salvaged not only into DNA but also into phospholipid
      precursors. III. dCOP-diacylglycerol formation in tonsillar lymphocytes.
AB  - In addition to the water-soluble deoxyliponucleotides (Spasokukotskaja et al.
      (1988), Biochem. Biophys. Res. Commun. 155, 923), a lipid compound was shown to
      be labeled from external 3H-deoxycytidine (5-3H-CdR) in infant tonsillar
      lymphocytes. Chlorpromazine enhanced the labeling of this compound, identified by
      TLC as 3H-dCDP-diacylglycerol (3H-dCOP-DAG). The deoxynucleotide salvage pathway
      seems to be the main source for dCDP-DAG synthesis, as hydroxyurea increased its
      labeling from CdR. myo-Inositol induced the disappearance of 5-3H-dCOP-DAG,
      suggesting its utilization for phosphatidylinositol synthesis. 3H-Arabinosyl
      Cytosine (araC) is also incorporated into the lipidic fraction at a rate
      comparable to its incorporation into DNA, supporting the effect of araC on
      membrane functions.

PMID- 1993064
TI  - Involvement of superoxide dismutase in heat-induced stimulation of photosystem I
      mediated oxygen uptake.
AB  - We have investigated the effect of heat-treatment of chloroplast thylakoid
      membranes on photosystem I-mediated electron transport. Spectroscopic techniques,
      oxidation of dichlorophenolindophenol (donor side) and reduction of NADP or
      methyl purple (acceptor side), showed no indication of an increased activity of
      photosystem I electron transport. Enhancement of oxygen uptake in the heat
      treated (40 degrees C-48 degrees C) samples could largely be accounted for by
      decline in the activity of superoxide dismutase.

PMID- 1993065
TI  - Human liver alcohol dehydrogenases catalyze the oxidation of the intermediary
      alcohols of the shunt pathway of mevalonate metabolism.
AB  - Human liver alcohol dehydrogenase (ADH) catalyzes the oxidation of 3,3
      dimethylallyl alcohol, the intermediary alcohol of the shunt pathway of
      mevalonate metabolism. ADH isozymes differ in their activities toward this
      alcohol in the order gamma 1 gamma 1 greater than gamma 2 gamma 2 approximately
      alfa alfa greater pi pi approximately beta 2 beta 2 approximately beta 1 beta 1
      much greater than chi chi; kcat/Km values are 1.4 x 10(8), 1.9 x 10(7), 1.4 x
      10(7), 5.6 x 10(6), 3.6 x 10(6), 1.6 x 10(6) and 2.5 x 10(3) M-1 min-1,
      respectively. The intermediary alcohols geraniol and farnesol of the proposed
      branch pathways of mevalonate metabolism are also oxidized by these isozymes with
      similar relative efficiencies. The genetic determinants of ADH isozymes may
      contribute to the observed differences in serum cholesterol levels among and
      within various populations.

PMID- 1993067
TI  - Transactivation of the human insulin receptor gene by the CAAT/enhancer binding
      protein.
AB  - Within human insulin receptor gene there are three consensus binding sites for
      the CAAT/enhancer binding protein (C/EBP). Two sites are located in the 5'
      flanking region and the other is in the first intron. We have studied the ability
      of these sequences to be regulated by C/EBP. A eukaryotic expression vector
      containing these sequences can be transactivated in a dose-dependent manner by a
      C/EBP expression vector when co-transfected into NIH-3T3 cells. In addition,
      double stranded oligonucleotides corresponding to two of these sequences can bind
      C/EBP in a gel retardation assay. These two oligonucleotides can complete with
      each other to bind C/EBP. These findings suggest that this transcription factor
      may play a role in the regulation of insulin receptor gene expression in vivo.

PMID- 1993066
TI  - A new heparin binding protein regulated by retinoic acid from chick embryo.
AB  - A 19 KDa heparin binding protein was previously purified from chicken embryos.
      Essentially localized within basement membranes in early embryonic tissues, this
      protein is very rich in basic and cystein residues. Its N-terminal fragment is
      similar to corresponding fragment of two other proteins expressed during
      embryogenesis and postnatal period. Its synthesis and secretion are induced by
      retinoic acid in chicken myoblasts and fibroblasts. This new retinoic acid
      induced heparin binding protein (RI-HB) does stimulate neurite outgrowth and
      proliferation on PC12 cells. These results suggest that retinoic acid could
      regulate some aspect of differentiation and development by inducing the synthesis
      of a new family of growth and neurotrophic factors.

PMID- 1993068
TI  - Mapping of carbohydrate sites on the human insulin receptor.
AB  - Prior to investigating the role of individual glycosylation sites in insulin
      receptor function, we are mapping the sites of glycosylation in the receptor. We
      report here a generally applicable methodology for the isolation and
      identification of glycosylation sites in cell surface glycoproteins. Human
      insulin receptors were labeled with [3H]-sugars using a CHO cell line transfected
      with the human receptor cDNA. Labelled receptors were mixed with receptors
      purified from human placental membranes and tryptic peptides prepared. Peptides
      were fractionated by gel filtration chromatography to limit the number of non
      glycopeptides present. Peptides were then separated by reverse phase HPLC and
      glycopeptides identified by scintillation counting. Using this technique we have
      shown the insulin receptor to be glycosylated at Asn 397 and Asn 881. This
      increase the known number of occupied glycosylation sites to five.

PMID- 1993069
TI  - Delineation of electric and magnetic field effects of extremely low frequency
      electromagnetic radiation on transcription.
AB  - The relative effects of the electric and magnetic field components of extremely
      low frequency electromagnetic radiation (ELF) on transcription were examined in
      human leukemia HL-60 cells. Delineation of the individual field contributions was
      achieved by irradiating cells in separate concentric compartments of a culture
      dish within a solenoid chamber. This exposure system produced a homogeneous
      magnetic field with a coincident electric field whose strength varied directly
      with distance from the center of the culture dish. Irradiation of HL-60 cells
      with sine wave ELF at 60 Hz and a field strength of 10 Gauss produced a transient
      increase in the transcriptional rates which reached a maximum of 50-60%
      enhancement at 30-120 minutes of irradiation and declined to near basal levels by
      18 hours. Comparison of transcription responses to ELF of cells in different
      concentric compartments revealed that the transcriptional effects were primarily
      the result of the electric field component with little or no contribution from
      the magnetic field.

PMID- 1993070
TI  - Prostaglandins antagonize fibroblast proliferation stimulated by tumor necrosis
      factor.
AB  - Tumor necrosis factor (TNF) is known to be a mitogen for human diploid FS-4
      fibroblasts. We have shown in an earlier study (Hori et al. (1989) J. Cell.
      Physiol. 141, 275-280) that indomethacin further enhances the cell proliferation
      stimulated by TNF. Since indomethacin inhibits the activity of cyclooxygenase,
      the role of prostaglandins in TNF-stimulated cell growth was examined. Cell
      growth stimulated by TNF and indomethacin was inhibited by exogenously added
      prostaglandins (PGE2, PGF2 alpha, and PGD2), among which PGE2 caused the greatest
      inhibition of cell growth. Treatment of FS-4 cells with 10 ng/ml TNF resulted in
      the release of prostaglandins (PGE2, 6-keto-PGF1 alpha, PGA2, PGD2, and PGF2
      alpha) 2 to 4 fold over that of untreated cells. The amount of all these
      prostaglandins increased in a time-dependent manner over 6 h after treatment. In
      both TNF-treated and control cells, PGE2 was released as the predominant
      prostaglandin. Furthermore, when PGE2 production and DNA synthesis were
      determined in FS-4 cells treated with increasing doses of indomethacin, these two
      cellular responses were inversely affected by indomethacin. These data show that
      prostaglandins induced by TNF antagonize growth stimulatory action of TNF.

PMID- 1993071
TI  - Phosphoramidon inhibits the intracellular conversion of big endothelin-1 to
      endothelin-1 in cultured endothelial cells.
AB  - Effects of various protease inhibitors on the conversion of big endothelin (ET)-1
      to ET-1 in cultured endothelial cells were analyzed. A metal protease inhibitor,
      phosphoramidon, decreases the amount of ET-1 and increase that of big ET-1
      released. This effect is dose-dependent and not nonspecific. When the contents of
      ET-1 and big ET-1 in the cells after culturing in the medium with or without
      phosphoramidon were measured, the ratio of ET-1: big ET-1 in the cells was 3.3 :
      1 and phosphoramidon inverted the ratio in the cells to 1 : 3.5. These data
      strongly suggest that a phosphoramidon-sensitive protease converts big ET-1 to
      mature ET-1 intracellularly.

PMID- 1993072
TI  - A calcium-activated protease from Alzheimer's disease brain cleaves at the N
      terminus of the amyloid beta-protein.
AB  - Alzheimer's disease, Down's syndrome, and to a far lesser extent, normal aged
      brains exhibit abnormal extracellular deposits of amyloid. The major component of
      brain amyloid is the beta-protein, a 4Kd fragment of the larger beta-protein
      precursor. The finding of the abnormally processed beta-protein and a protease
      inhibitor (alpha 1-antichymotrypsin) in the amyloid deposits prompted us to
      search for proteases which may generate the beta-protein from its precursor. We
      now report on the presence and partial purification of one such proteolytic
      activity from Alzheimer's brain. Normal physiologic C-terminal cleavage of the
      secreted form of the beta-protein precursor occurs in the middle of the beta
      protein suggesting that the beta-protein accumulates due to an alternative
      degradation pathway. We propose here that the protease activity we describe
      participates in this abnormal pathway.

PMID- 1993073
TI  - Induction of putative new cytochrome P450 isozyme in rat liver by 2-amino-1
      methyl-6-phenylimidazo[4,5-b]pyridine.
AB  - Changes in hepatic enzymes responsible for mutagenic activation of food mutagens
      carcinogens by treatment with 2-amino-1-methyl-6-phenylimidazo [4, 5-b]pyridine
      (PhIP) in male F344 rats were examined using the Salmonella mutation test, with 3
      heterocyclic aromatic amines as substrates, and further characterized by Western
      blot analysis with anti-P450 monoclonal antibodies (MoAbs) against rat P450IA1
      and P450IA2. Enzymatical and immunochemical analyses indicated that PhIP could
      induce a putative new P450 isozyme, mol. wt., 51,000, together with P450IA1 and
      P450IA2 in rat liver microsomes. The profiles of induced P450 molecular species
      varied dramatically, depending on the time after PhIP administration.

PMID- 1993074
TI  - Cathepsin D gene of human MCF7 cells contains estrogen-responsive sequences in
      its 5' proximal flanking region.
AB  - Cathepsin D is a lysosomal protease produced and secreted in excess by most human
      breast cancer cells. In MCF7 cells, estrogens stimulate cathepsin D expression at
      the mRNA level via a mechanism independent of de novo protein synthesis. We have
      isolated the human cathepsin D gene and its 5' flanking sequences from a MCF7
      genomic library. To demonstrate its transcriptional estrogen regulation, we
      constructed chimeric recombinants bearing different fragments of the cathepsin D
      gene 5' proximal region inserted in front of the bacterial chloramphenicol acetyl
      transferase reporter gene. By transient cotransfection with the estrogen receptor
      expression vector into MCF7 cells, we showed that a 240 bp fragment located in
      the 5' proximal region of the gene was able to mediate transcriptional estrogen
      activation. This induction was concentration-dependent and suppressed by the
      antiestrogen ICI 164, 384.

PMID- 1993075
TI  - The estrogen-regulated destabilization of Xenopus albumin mRNA is independent of
      translation.
AB  - Protein synthesis inhibitors have been shown to increase the stability of a
      number of labile mRNAs. In Xenopus laevis serum albumin mRNA is destabilized in
      the liver cell cytoplasm following estrogen administration. The present study
      examined the effect of translation inhibitors on this process. The initiation
      inhibitor 2-(4-methyl-2,6-dinitroanilino)-N-methylpropionamide causes
      accumulation of albumin mRNA in 20-80S mRNP particles whereas the elongation
      inhibitor cycloheximide causes albumin mRNA to accumulate in polysomes. Neither
      inhibitor blocked the disappearance of albumin mRNA from liver cell cytoplasm
      when added with estradiol to the medium of liver explant cultures. We conclude
      that unlike a number of labile mRNAs the instability of Xenopus albumin mRNA
      following estradiol is independent of translation.

PMID- 1993076
TI  - High level expression and purification of dthymidine diphospho-D-glucose 4,6
      dehydratase (rfbB) from Salmonella serovar typhimurium LT2.
AB  - The rfbB gene (dThymidine-diphospho-D-glucose-4,6-dehydratase) from Salmonella
      serovar typhimurium LT2 was cloned and over-expressed using the T7 RNA
      polymerase/promoter system. The expressed protein, which represents almost 10% of
      the total cellular protein was purified 14-fold. dTDP-D-glucose 4,6-dehydratase
      is a homodimer of 43 kDa subunits, is highly specific for dTDP-D-glucose and
      shows a Km of 427 microM and Vmax of 0.93 mu moles min-1 micrograms-1 of protein
      for dTDP-D-glucose. The N-terminal analysis confirmed the start position of the
      gene in the DNA sequence. Complete deactivation of the enzyme by the addition of
      p-chloromercurisulfonic acid and total reactivation by the addition of
      mercaptoethanol, co-factor NAD+ and cystein showed that a -SH group of the
      cysteine is involved in the catalytic site.

PMID- 1993077
TI  - Mutagenesis of human fibrinogen gamma chain 259-411 synthesized in E. coli:
      further characterization of the role of the disulfide bond CYS326-CYS339 in
      calcium binding.
AB  - We have produced human fibrinogen gamma 259-411 in Escherichia coli in order to
      study the relationship between the calcium binding activity of the polypeptide
      and the integrity of the disulfide bond cysteine326-cysteine339. The polypeptide
      was produced from a plasmid expression vector at approximately 5 micrograms per
      milliliter of bacterial culture. The identity of the polypeptide was confirmed by
      N-terminal amino acid sequence analysis. The expression vector was modified by
      oligonucleotide directed mutagenesis to remove the nucleotides encoding cysteines
      gamma 326 and gamma 339. The calcium binding activity of wild-type and altered
      polypeptides were compared using a solid phase assay. Our results indicate that
      removal of the two cysteine residues had no appreciable effect on calcium binding
      activity. We conclude that the integrity of the disulfide bond cysteine326
      cysteine339 is not critical for calcium binding to gamma 259-411.

PMID- 1993078
TI  - Structural flexibility of Aib-containing peptides: the N-terminal tripeptide of
      trichotoxin.
AB  - The sequence Aib-Gly-Aib which corresponds to the N-terminus of the
      microheterogeneous peptide antibiotic trichotoxin has been studied
      crystallographically in the context of different protecting groups. Peptides Ac
      Aib-Gly-Aib-OH (A) and Z-Aib-Gly-Aib-OH (B) form beta-turns. Both peptides show a
      remarkable conformational flexibility forming a large variety of beta-turns of
      different types.

PMID- 1993079
TI  - IGG-stimulated and LPS-stimulated monocytes elaborate transforming growth factor
      type beta (TGF-beta) in active form.
AB  - Mononuclear cells (MNC) stimulated either with lipopolysaccharide (LPS) or with
      surface-adsorbed IgG elaborated significant amounts of tumor necrosis factor
      (TNF) bioactivity, as well as immunoenzymatically detectable TNF-alpha and
      interleukin-1 beta. (IL1-beta). In contrast, IgG-stimulated cells released little
      IL1 bioactivity, but released an IL1 inhibitor, as determined by the thymocyte
      costimulatory assay (LAF assay). This inhibition was not due to an inhibitory
      effect of cyclooxygenase products, e.g. prostaglandin-E2 in the LAF assay. In
      contrast, antibodies against transforming growth factor type beta (TGF-beta),
      which is an important inhibitor of the LAF assay, augmented the LAF activity of
      supernatants from LPS-stimulated and IgG-stimulated MNC. Anti-TGF-beta-modulated
      LAF inhibition was enhanced by acid treatment of supernatants from mononuclear
      cells, but not of those from purified monocytes. Antibody blocking experiments
      point for the first time to a TGF-beta species other than type 1 as a monocyte
      derived TGF-beta activity. Thus, TGF-beta released in active form from monocytes
      may be the more important antagonist of IL1 than cyclooxygenase-derived
      mediators. It implies that the LAF assay, in the absence of anti-TGF-beta
      antibodies, is an inadequate indicator of IL1 activity.

PMID- 1993080
TI  - Isolation and properties in culture of human adrenal capillary endothelial cells.
AB  - The isolation of human adrenal capillary endothelial (HACE) cells without resort
      to fluorescence activated cell sorting is described, together with their
      properties in culture. HACE cells were isolated by plating collagenase digests at
      high dilution in the presence of endothelial cell growth supplement, followed by
      clonal selection of endothelial colonies. HACE cells exhibit a typical
      endothelial 'cobblestone' morphology at confluence and formed 'tubes' when seeded
      onto 'Matrigel'. They are positive for human MHC1, and the endothelial markers
      ENDOCAM (CD31) and weakly CD34, they also take up dil-acetyl low density
      lipoprotein but are negative for Factor VIII. Their growth is strongly stimulated
      by FGF and inhibited by TGF-beta I. Like their much studied bovine counterparts
      they are robust in culture, retaining the properties described up to senescence.
      HACE cells provide a readily available alternative to human umbilical vein
      endothelial cells in that they are easily isolated pure and in quantity. They
      should be particularly useful in studies where human capillary, as opposed to
      large vessel endothelium, is required.

PMID- 1993082
TI  - The isolated cytoplasmic domain of band 3 binds calcium at physiological salt
      concentration and neutral PH.
AB  - Calcium is known to be a potent but partial intracellular inhibitor of band 3
      anion exchange. Here we test the hypothesis that the cytoplasmic domain of band 3
      (CDB3) contains a calcium binding site. Calcium binding to CDB3 was monitored by
      measuring the formation of the Aresenazo III-calcium complex at various constant
      CDB3 concentrations. These experiments were performed at physiological salt and
      neutral pH. The calcium-CDB3 dissociation constant was estimated to be less than
      or equal to 24 microM. We also found that the Arsenazo III-calcium complex binds
      to CDB3, while the free dye does not bind. We conclude that CDB3 contains a site
      which is capable of binding free calcium under physiological conditions. A
      specific role for this site in inhibition of band 3 anion exchange is suggested,
      but that role remains to be established.

PMID- 1993081
TI  - Effect of cell density on induction of growth hormone receptors by dexamethasone
      in primary cultured rat hepatocytes.
AB  - The effect of cell density on the regulation of growth hormone (GH) receptors was
      studied by measuring specific binding of [125I]hGH to primary cultured
      hepatocytes with or without dexamethasone, which induces GH receptors. In cell
      cultures without dexamethasone, the cell density did not affect the level of
      binding of labeled GH appreciably. On the other hand, in the presence of
      dexamethasone, which induced an increase in the level of GH receptors on the
      cells, GH-binding by cultured cells at low cell density (3.3 x 10(4) cells/cm2)
      was about one-third of that of cells at high cell density (10(5) cells/cm2).
      Scatchard plot analysis showed that the cell-density dependent change in
      induction of GH binding, by dexamethasone was due to change in the number of
      binding sites without significant change in their affinity. The binding capacity
      of glucocorticoid receptors, measured as specific binding of [3H]dexamethasone to
      the hepatocytes, was not significantly affected by cell density. These results
      suggest that cell density modulates GH receptor induction by dexamethasone via
      events after glucocorticoid receptor binding.

PMID- 1993083
TI  - Purification and partial sequence analysis of the soluble catechol-O
      methyltransferase from human placenta: comparison to the rat liver enzyme.
AB  - Catechol-o-methyltransferase from human placenta was purified 1400-fold by
      hydroxyapatite adsorption, ammonium sulfate precipitation, gel filtration, high
      performance anion- exchange and reversed-phase chromatography. The purified
      enzyme has an apparent molecular weight of 26.000, an isoelectric point of 5,3
      and is activated ten-fold in the presence of 20mM cysteine. The enzyme shows
      primary structure homology to the corresponding rat liver soluble enzyme, based
      on the sequenced tryptic peptides.

PMID- 1993084
TI  - A strategy for health promotion at multiple corporate sites.
AB  - 1. The logistical problems associated with delivery of health promotion programs
      at multiple corporate sites can be addressed through the use of health education
      packets. 2. The role of the nurse or health coordinator is critical in assisting
      and guiding the employee as the health plan is executed. 3. Problematic areas
      related to implementation of programs at remote sites can be alleviated through
      careful planning and extensive communication. 4. Advertising, input from
      employees and staff, and follow up are important in the success of a program.

PMID- 1993086
TI  - Health objective series. Stress management consulting for workplace mental health
      and wellness.

PMID- 1993085
TI  - Worksite health promotion. The benefits of providing personal health status
      feedback and education programs to employees.
AB  - Discovering ways to initiate and maintain health related behavior changes is a
      growing concern to business and industry. This research supports previous data
      indicating that wellness programs offered at the worksite are significantly
      beneficial in assisting employees to change behavior. This research did not find
      significant benefits to the employees who obtained health status information
      prior to participating in a worksite health program; however, the health
      assessment tool was informative and may have been adequate to assist in behavior
      changing activities. Wellness programs are important factors for promoting health
      related behaviors; failure of this study to support the importance of assessment
      feedback does not negate the desirability of assessment as an important component
      of the corporate wellness program.

PMID- 1993087
TI  - Employee experiences with early return to work programs.
AB  - Those who administer early return to work programs should be aware of the
      differing needs of workers who have suffered on the job injuries. Many employees
      are able to move through a program without problems; others are at risk for poor
      outcomes. Those workers most in need of assistance should an on the job injury
      occur are those who have relatively poor satisfaction in the job in which injury
      occurred, a longer period of disability due to injury, aggravation of injury
      while on the early return to work program, or perceptions of little support from
      within the company. Particular attention to certain aspects of programs
      (identification of workers at risk for poor outcome, design of modified jobs, and
      communication of concern for workers) may enhance favorable response to early
      return to work programs.

PMID- 1993088
TI  - Thermal modalities: heat and cold. A review of physiologic effects with clinical
      applications.
AB  - Thermal modalities are safe, simple, inexpensive, and easily taught for self
      application. Their efficacy has been demonstrated in anecdotal, clinical, and
      basic physiological research reports. Topical thermal modality application has
      potential therapeutic effects on three areas of physiologic functions in soft
      tissue disorders: 1) Local circulation/metabolism; 2) Local neuromuscular and
      musculotendinous function; and 3) Nociception, including local and central neural
      activity. Knowledge of the physiology of the modalities and the pathophysiology
      of these disorders enables the occupational health nurse to use them
      appropriately. Topical heat application is often more easily accepted, while cold
      application is less favorably accepted. Physiological findings, however, indicate
      that, for topical application, cold application has much greater potential for
      restorative, therapeutic effect, while topical heat is almost exclusively limited
      to palliative effects. By educating and encouraging employees in the self
      application of these modalities the occupational health nurse promotes self
      efficacy in health care, providing an alternative to reliance on prescription or
      OTC medications.

PMID- 1993089
TI  - Licensure and entry into nursing practice. A survey of occupational health
      nurses' opinions.
AB  - Since 1965, the controversial question of what level of educational preparation
      is appropriate and necessary for entry into nursing practice has been discussed.
      No consensus has been reached by the members of the nursing profession as a
      whole. The opinions of occupational health nurses toward the requirement for
      initial registered nurse licensure and entry into occupational health nursing
      practice was assessed. The study revealed occupational health nurses generally
      supported their respective basic programs for initial licensure and entry into
      occupational health nursing.

PMID- 1993090
TI  - Confidentiality and the employee assistance program professional.
AB  - During the last two decades EAPs have offered employees confidential assessment,
      counseling, and referral. Many occupational health nurses have taken on the role
      of EAP professional or function as the liaison between the EAP counselor and the
      employee. The occupational health nurse involved in any EAP issue must adhere to
      the standards of confidentiality. The federal and state laws, company policy, and
      professional codes of ethics regarding these clients must be clearly understood,
      especially related to the issue of confidentiality.

PMID- 1993091
TI  - Nurse questions salary data.

PMID- 1993092
TI  - Effects of an expanded medical curriculum on the number of graduates practicing
      in a rural state.
AB  - In 1973 the University of North Dakota School of Medicine (UNDSM), following the
      national trend toward four-year medical programs, expanded its previous two-year
      medical school curriculum to include all four years of medical education. It was
      hoped that this change, along with a renewed emphasis on primary care-oriented
      residency training within the state, would encourage medical students to
      establish practices within the state. In 1985 the UNDSM's Center for Rural Health
      mailed questionnaires to the 2,230 living graduates of the UNDSM to document a
      variety of their personal and practice characteristics. Based on the responses to
      the 924 completed questionnaires, the authors found that (1) the students from
      rural North Dakota were more likely than were urban students to practice in rural
      areas of the state, as were the students with primary care specialty training;
      and (2) the alumni completing residencies in North Dakota following the
      curriculum expansion (1976-1985) were more than twice as likely to establish
      practices in North Dakota. It was concluded that recruiting medical students
      (preferably in-state "natives") from rural areas, training them in primary care
      specialty areas, and enabling them to remain in North Dakota for the duration of
      their medical training (including residency training) combined to exert a
      considerable "retaining" effect on the UNDSM alumni.

PMID- 1993093
TI  - Clinical behaviors and skills that faculty from 12 institutions judged were
      essential for medical students to acquire.
AB  - This paper describes a 1988-1989 collaborative mail survey of faculty opinion
      about clinical behaviors and skills that students should be expected to
      demonstrate prior to graduation from undergraduate medical school (hereafter
      called "exit objectives"). Selected faculty from 12 American and Canadian medical
      schools indicated whether each of 77 objectives was essential for every student
      to know or demonstrate prior to graduation; useful but not essential at the
      undergraduate level; or not applicable to their undergraduate program. Their
      responses provide a glimpse into faculty expectations regarding some of the exit
      behaviours and skills they deemed essential. Forty-two percent (32) of the 77
      objectives were regarded as essential by 75% or more of the faculty members who
      responded. Essential objectives involved conducting organ system examinations,
      formulating problems and hypotheses, and gathering fundamental interview,
      physical, and screening examination data, including emergency examinations of the
      airway and circulatory systems. Other essential objectives involved collaboration
      and communication, demonstrating concern for legal and ethical values, and
      keeping abreast of current information within the discipline. Exit objectives
      related to the diagnosis and management of specific conditions were regarded as
      useful but not essential at the undergraduate level. Implications for medical
      education are discussed.

PMID- 1993094
TI  - A prospective study of internal medicine residents' emotions and attitudes
      throughout their training.
AB  - To evaluate whether the negative emotions and attitudes that residents develop
      during internship continue throughout the remaining years of their residency, the
      authors undertook a four-year prospective study of two classes of internal
      medicine residents who completed their training in 1985 and 1986 in a residency
      program based at the Oregon Health Sciences University. Every two to three months
      over all three years of training, the residents indicated on Likert-type scales
      their levels of agreement with questions about their career satisfaction and
      emotional states, and the satisfying and dissatisfying aspects of their residency
      experiences. Between the internship and the end of their residencies, the
      physicians indicated significant improvements in their emotions and attitudes.
      Those experiences identified as satisfying continued to be so, whereas those
      considered dissatisfying became less so. Although more research of other classes
      of residents is needed, the findings suggest that while internal medicine
      internships may be dysphoric, the residents' emotional states and attitudes tend
      to normalize during the remainder of the residency.

PMID- 1993095
TI  - A model of a microcomputer database system to assist medical schools in
      recruiting and retaining students.
AB  - A model for a microcomputer database to aid a school's efforts to recruit and
      retain students is presented. The model is based upon a working system developed
      by the author at the University of Colorado Health Sciences Center. The article
      discusses data needs for adequate records of the recruitment and retention
      efforts, especially those concerning minority students, and how these records can
      be used to administer and evaluate programs. The model provides a framework for
      microcomputer data files, record fields, relationships, and system development
      and maintenance considerations.

PMID- 1993096
TI  - U.S. residency directors' views of the importances of seven roles that pediatrics
      residents should master.
AB  - Pediatrics residency programs should define and evaluate for their residents and
      faculty the competencies that residents should acquire during their three years
      of training. This 1987 survey of 129 pediatrics residency directors sought data
      about the demographic characteristics of the programs and asked the program
      directors to what degree they agreed that seven roles (each comprising several
      competencies) of the general and ambulatory-care pediatrician were essential.
      There was strong agreement on the seven roles and no demonstrated association
      between these responses and the residency programs' university affiliations,
      types of facilities, ages, lengths of training, or geographic locations. The
      results of this survey may be useful in developing ways to document and evaluate
      residents' performances and define subspecialty objectives that are consistent
      with the seven basic roles.

PMID- 1993097
TI  - Faculty attitudes toward various teaching formats at two Canadian medical
      schools.

PMID- 1993098
TI  - Time spent by preceptors on specific educational activities in inpatient and
      ambulatory-care settings.

PMID- 1993099
TI  - Reasons that medical students seek psychiatric assistance.

PMID- 1993100
TI  - A follow-up of a program to foster medical students' interest in research and
      academic careers.

PMID- 1993101
TI  - Using pharmaceutical advertising in medical education.

PMID- 1993102
TI  - Financing medical education.
AB  - The cost of a medical education may dissuade qualified young people from entering
      the medical profession or may so load them with debt that they cannot pursue
      relatively low-paid careers in primary care or clinical investigation. Three
      aspects of this problem are examined: (1) the cost of medical school, (2) the
      magnitude of student indebtedness, and (3) the effects of this indebtedness on
      career choices. High tuition and fees require many students to assume sizable
      educational debts, some of which are so large that the trainees will be unable to
      repay them unless they enter highly remunerative specialties. Also, high levels
      of indebtedness may increase default levels once graduates feel the full impact
      of scheduled repayments. Several steps would help to alleviate this problem, but
      are unlikely to solve it. First, medical schools should lower tuition or at least
      declare a moratorium on increases. Second, limits should be imposed on the amount
      of total education debt a student is allowed to assume. Third, hospitals with
      extensive residency programs should assume some responsibility for helping
      trainees manage their finances. Fourth, the government should institute a loan
      forgiveness program that addresses the need for physician-investigators, primary
      care physicians, those willing to practice in underserved areas, and those from
      underrepresented minorities. And fifth, all institutions involved in medical
      training and its finance should work together to advise students on managing
      their debts.

PMID- 1993103
TI  - Shaping national science policy: some lessons learned.
AB  - Thirty-five years of experience have taught several lessons about shaping science
      policy. Derived from these lessons are four premises that deserve individual and
      collective thought: (1) The partnership in U.S. society between health and
      science interests is fundamentally important; (2) Scientific merit must be the
      paramount basis for allocating whatever research funds are available; (3) Better
      data and their careful analysis are vital to the decision-making processes; and
      (4) More than ever we must have a clear, concise, vigorous, and repeated
      enunciation of the principles that are essential for a national biomedical
      research program to flourish. The fourth premise is expressed succinctly in the
      11 principles outlined in the 1983 AAMC monograph "Preserving America's
      Preeminence in Medical Research," which places important responsibilities for the
      collective success of the U.S. research program on all of the various components
      of society. Three important factors favor efforts to shape a useful, successful
      science policy: a public that places improvements in health high on every
      priority list, a rapidly expanding body of invaluable knowledge, and a sizable
      investment of tax-derived funds, now totalling over $7.5 billion per year.

PMID- 1993104
TI  - Forty years of litigation involving medical students and their education: II.
      Issues of finance.
AB  - An analysis of reported state and federal adjudication from 1950 through 1989 was
      undertaken to identify trends in litigation involving medical students and
      undergraduate medical education. Of the 110 cited judicial decisions during that
      time, 59 (54%) involved disputes over financing medical education; 43 (73%) were
      litigated since 1985. This dramatic increase arises primarily from challenges to
      National Health Service Corps obligations and from attempts to discharge or
      reorganize debt under the Bankruptcy Code. Medical school graduates enjoyed very
      little success in these cases. Analysis of court decisions points to a need for
      informed counseling for medical students, particularly as to the consequences of
      timing in default on service obligations and of incurring loans under the Health
      Education Assistance Loan (HEAL) program as opposed to other loan sources. The
      growing educational debt of today's medical students foreshadows continued
      litigation in this area.

PMID- 1993105
TI  - Teaching medical students a developmental approach to examining patients.

PMID- 1993106
TI  - A survey of American medical schools to assess their preparation of students for
      overseas practice.

PMID- 1993107
TI  - The NIH management plan.

PMID- 1993108
TI  - The current status and future of VA research.
AB  - The VA Advisory Committee for Health Research Policy concluded that the health
      research aspect of departmental operations is vital to the VA's continued ability
      to provide high-quality health and medical care. The quality of VA-sponsored
      research in all areas remains high and on a par with that supported by the NIH
      and other governmental agencies sponsoring health research. Recent decreases in
      the financial support of VA research, however, have led to the unwise curtailment
      of VACO research staff support for this program, have reduced the number of
      approved projects that can be funded (though there has been a fourfold increase
      in the number of approved but unfunded projects), and are likely to reduce the
      attractiveness of VA employment for highly qualified physicians. In view of these
      findings, the committee recommended several steps that, if found feasible and
      taken soon, would both restore the long-standing stature of VA research and
      assure the attractiveness of VA careers for the many clinician-investigators upon
      whom the VA's quality of patient care necessarily depends.

PMID- 1993109
TI  - Preparing students for overseas electives.

PMID- 1993110
TI  - A committee report on vacant chairs of pharmacology.

PMID- 1993111
TI  - Accommodating to restrictions on residents' working hours.
AB  - In 1988, New York became the first state to implement regulatory measures
      limiting housestaff work hours. Because restrictions on residents' work hours
      will have such profound and far-reaching implications for how obstetrics and
      gynecology residencies are conducted, the Council on Resident Education in
      Obstetrics and Gynecology (CREOG) requested that a survey be conducted to solicit
      information from program directors of U.S. obstetrics and gynecology residencies
      who had already begun to alter their call schedules. Two hundred and ninety-six
      programs were contacted, and representatives of those that had implemented
      changes were requested to respond. Eighty-two responses were received; 26 of
      these contained information that could be collated. From these 26 responses the
      authors have structured a prototypic call schedule and presented its application.
      A key feature necessary to implement the new type of schedule is the use of a
      night float system. It is concluded that changes can and will be made by
      obstetrics and gynecology residencies. Creative scheduling, as described in this
      article, is essential and will facilitate the task; however, the current
      standards of education and patient care will be difficult to maintain without
      additional economic and human resources.

PMID- 1993112
TI  - The uses and value of autopsy in medical education as seen by pathology
      educators.
AB  - A national meeting of pathology educators in 1989 provided the impetus for an
      exploration of new uses of autopsy in medical education. A month before the
      conference, the authors sent a questionnaire about the uses and value of autopsy
      in medical education to 120 persons registered to attend the conference. They
      used the 98 responses, representing 69 U.S. and Canadian medical schools, as the
      basis of a workshop on the place of autopsy in future medical education. The
      present article is a report of the authors' findings from the questionnaire and
      workshop. They found that the uses of autopsy go far beyond the traditional uses
      in teaching clinical pathophysiology, clinico-pathologic correlations, clinical
      anatomy, gross and microscopic anatomy of disease, and visual skills. Emphasis
      was placed on the potential role of autopsy in education regarding legal/judicial
      proceedings, vital statistics, epidemiologic investigations, and public health,
      and in the understanding of such complex matters as medical fallibility, medical
      uncertainty, and grief. These purposes were seen as congruent with current
      societal concerns about the need to reverse the trend toward dehumanization of
      medicine and physicians. The inability to realize these aims in the face of a
      precipitous drop in the autopsy rate is discussed.

PMID- 1993113
TI  - Cationic antigens as mediators of inflammation.
AB  - Electrical charge is an important determinant of antigen deposition in tissue.
      Cationic antigens can bind to anionic sites found in many organs. The major focus
      of interest has been the renal glomerulus and the articular joint. Experimental
      models of immune complex glomerulonephritis and allergic arthritis were
      established with chemically cationized proteins. More recently the concept has
      been extended to natural cationic proteins and human disease. The histones were
      shown to be potent initiators of experimental immune complex nephritis and
      convincing evidence for their participation in both murine and human lupus
      nephritis was obtained. Evidence is also presented that cationic proteins from
      Borrelia burgdorferi and Yersinia enterocolitica may participate in the reactive
      arthritis associated with these bacteria. Eucaryotic and prokaryotic nucleic acid
      binding proteins were identified as prime candidates for causing both immune
      complex glomerulonephritis and antigen-induced allergic arthritis.

PMID- 1993114
TI  - Isolation and characterization of a soluble antigen complex of Plasmodium
      falciparum with pyrogenic properties.
AB  - A soluble antigen complex, previously designated antigen no. 7 (Ag7) on the basis
      of the pattern obtained by crossed immunoelectrophoresis of culture supernatants
      of P. falciparum, was isolated by affinity chromatography. It was shown to be
      synthesized at the schizont stage of the parasite growth cycle and to be located
      on the surface of the schizonts. Antibodies to Ag7 did not inhibit the growth of
      the parasite in vitro. Ag7 is recognized by immune human sera from many parts of
      the world and it stimulated the production of specific antibody in mice when
      incorporated into immune-stimulating complex (ISCOM) structures. It also
      specifically stimulated in vitro proliferation of lymphocytes from clinically
      immune adults. That it induced the secretion of interleukin 1 by human monocytes
      and was pyrogenic in rabbits was of particular interest. Thus Ag7 has endotoxin
      like properties which make it a possible candidate for an antitoxic malaria
      vaccine.

PMID- 1993115
TI  - Viral RNA species in cell lines persistently and lytically infected with measles
      virus.
AB  - Identical measles viral mRNA species were present in similar amounts in the
      persistently infected cell lines LU106, HEpPi and MaSSPE, and in lytically
      infected cells as determined from Northern blots. The attenuation of
      transcription with the gene order did not vary significantly between different
      infected systems. A previously described selective restriction of F protein
      production in Lu106 cells could not be explained by defective transcription of F
      mRNA. RNA synthesis also continued unimpeded at restrictive temperatures for the
      temperature-sensitive viruses in Lu106 and HEpPi cells. Northern blotting
      revealed a prominent band in HEpPi RNA and a weak band in Lu106 RNA with the
      characteristics of incomplete genomes. In all infected cells, previously
      unrecognized small RNA species, hybridizing with the F- and H-specific probes,
      were discovered.

PMID- 1993116
TI  - Hypersensitivity of delayed type in hypertensive patients.
AB  - The agarose migration technique was used for demonstration of delayed-type
      hypersensitivity to arterial vessel wall antigens in patients suffering from
      chronic essential hypertension. By means of this technique, it was demonstrated
      that the migration indices from the hypertensive patients differed significantly
      from the normotensive control persons, P less than 0.005. The significant
      difference was abolished when anti-LIF was added to the migration tests. This
      means that a hypersensitivity of the delayed type had developed in the
      hypertensive patients and the results indicated that the hypersensitivity was an
      autoimmunity to arterial vessel wall antigens.

PMID- 1993117
TI  - Immune response in chlamydial conjunctivitis among neonates and adults with
      special reference to tear IgA.
AB  - Tear and serum samples from 128 neonates and 122 adults with conjunctivitis were
      examined for antibodies to Chlamydia trachomatis with a micro-immunofluorescence
      (MIF) technique and the results compared to antigen detection by culture, enzyme
      immunoassay (EIA) (Chlamydiazyme, Abbott) and direct immunofluorescence (IF)
      (MicroTrak, Syva and Chlamyset, Orion) tests. From the 52 culture-positive
      adults, chlamydial IgA (titre greater than or equal to 1:8) antibodies were
      detected in 81% of the tear and in 62% of the serum samples, while 88% had such
      serum IgG antibodies (titre greater than or equal to 1:32). The persistence of
      chlamydial IgA in tears and sera was related to the duration of symptoms of
      conjunctivitis and the antibody titres declined after institution of antibiotic
      treatment. In the adults, the sensitivity of the MIF tear IgA antibody test (81%)
      was higher than that of the EIA (71%) and the IF (MicroTrak 71% and Chlamyset
      62%) tests. The specificity for the MIF test was 79%, while it was 100% for the
      EIA and the two IF tests. Of the 67 chlamydia-infected neonates, 36% had
      chlamydial tear IgA antibodies, while such antibodies were only found in 15% of
      the sera. No neonates with chlamydia-negative conjunctivitis had chlamydial IgA
      antibodies. The MIF test may be used as a diagnostic method complementary to
      culture, EIA and IF tests in the diagnosis of chlamydial conjunctivitis in
      adults, but is not applicable in neonates.

PMID- 1993118
TI  - Fatal septicaemia with Selenomonas sputigena and Acinetobacter calcoaceticus. A
      case report.
AB  - A 38-year-old man with a history of alcohol abuse developed rapidly fulminating
      septicaemia and died. Selenomonas sputigena and Acinetobacter calcoaceticus were
      isolated from a blood culture. Selenomonas sputigena is a motile anaerobic gram
      negative rod rarely associated with systemic disease. Difficulties in isolation
      and taxonomic identification are discussed.

PMID- 1993119
TI  - Age and sex distribution of intestinal type and diffuse gastric carcinoma.
AB  - A twelve-year series of 375 patients with gastric carcinoma has been studied.
      Primary tumours were classified as intestinal type (58%) or diffuse (26%),
      whereas 16% were unclassifiable. The relative age and sex incidence rates of
      intestinal type and diffuse gastric carcinoma were estimated using the age and
      sex distribution of individuals in Norway as the basis for calculation. There was
      no difference in the rates of diffuse gastric carcinoma between the sexes. On the
      other hand, the rate of men with intestinal type carcinoma was more than twice as
      high as that of women. This difference was consistent within each age group from
      adolescence to senescence. The findings indicate that Lauren's two types of
      gastric carcinoma are aetiologically different. The rates of both types increased
      with age up to the 70-79 age group, whereas the rates in octogenarians tended to
      be lower than in septuagenarians. A comparison of our data with the data of
      incidence of gastric cancer in Norway indicates that some of the older patients
      do not come for surgery.

PMID- 1993120
TI  - Crossed immunoelectrophoretic analysis of Mycobacterium paratuberculosis.
AB  - Antigenic analysis of M. paratuberculosis revealed extensive cross-reactivity
      with M. avium; however, the number of cross-reactive antigens found was dependent
      on the strain of M. avium tested. One antigen was shown to be the common antigen
      while another appeared to be iron-regulated in its production. A commercial
      polyclonal antibody to M. paratuberculosis produced a CIE precipitin pattern
      comparable to that of the antibody produced for the present study. An antigen
      designated no. 6 was consistently precipitated by sera from cattle infected with
      M. paratuberculosis. This antigen exhibited complete cross-reaction with M. avium
      and partial cross-reaction with M. phlei. Among three commercially available
      complement fixation (CF) antigen that could be precipitated by M.
      paratuberculosis antibodies. A commercial antigen for use in an agar gel
      immunodiffusion test for Johne's disease diagnosis produced 12 precipitins with
      the M. paratuberculosis antibody, one of which was identical with antigen 6.

PMID- 1993121
TI  - Congenital earpits or auricular sinuses.
AB  - Congenital earpits or auricular sinuses are defects in the development of the
      outer ear from the 1st and 2nd branchial arch. They are most often located in
      front of the ear. Six cases are described. Early surgery is recommended because
      of a tendency towards infection with scarring. They can be associated with
      serious internal abnormalities, especially deafness and kidney malformations.

PMID- 1993122
TI  - Neurite outgrowth in response to transfected N-CAM and N-cadherin reveals
      fundamental differences in neuronal responsiveness to CAMs.
AB  - Different neuronal populations were used to compare the neurite outgrowth
      promoting activities of N-CAM and N-cadherin expressed via gene transfer on the
      surface of nonneuronal cells. In contrast to a previously reported developmental
      loss of retinal ganglion cell responsiveness to N-CAM, these cells exhibited an
      increased and maintained responsiveness to N-cadherin over the same developmental
      period (E6-E11). N-CAM and N-cadherin responses could be specifically inhibited
      by their own antibodies, but not by antisera to the beta 1 integrin family or the
      L1/G4 glycoprotein. Cerebellar neurons showed qualitative differences in the
      nature of the dose-response curves for transfected N-CAM expression (highly
      cooperative) versus N-cadherin expression (linear). In addition "subthreshold"
      levels of N-CAM expression, which do not normally support neurite outgrowth, did
      so when coexpressed with functional levels of N-cadherin. These studies show
      fundamental differences in neuronal responsiveness to cell adhesion molecules and
      suggest a more dynamic regulation for N-CAM-dependent neurite outgrowth than for
      N-cadherin-dependent outgrowth.

PMID- 1993123
TI  - Opioids activate both an inward rectifier and a novel voltage-gated potassium
      conductance in the hippocampal formation.
AB  - Opioid receptors were found to activate two different types of membrane potassium
      conductance in acutely dissociated neurons from the CA1/subiculum regions of the
      adult rat hippocampal formation. Opioid-responsive neurons were distinguished
      based on their morphology and electrophysiological responses. In one population
      of neurons having a multipolar, nonpyramidal cell shape, mu-selective opioid
      agonists increased an inward rectifying potassium current. Opioid activation of
      the inward rectifying conductance resulted in small outward potassium currents at
      resting membrane potentials and increased inward currents at hyperpolarized
      potentials. In a second population of nonpyramidal neurons, mu opioid agonists
      increased a novel voltage-gated potassium current. This current was blocked by
      internal CsCl2, unaffected by external BaCl2 or CdCl2, irreversibly activated by
      intracellular GTP-gamma-S, and inactivated by sustained depolarization. In
      contrast to the inward rectifying conductance, the voltage-gated conductance was
      not activated at resting membrane potentials or hyperpolarized potentials. The
      opioid-activated, voltage-gated conductance represents a new class of G protein
      regulated potassium current in the brain.

PMID- 1993124
TI  - Molecular mechanisms separating two axonal pathways during embryonic development
      of the avian optic tectum.
AB  - During embryonic development of the avian optic tectum, retinal and tectobulbar
      axons form an orthogonal array of nerve processes. Growing axons of both tracts
      are transiently very closely apposed to each other. Despite this spatial
      proximity, axons from the two pathways do not intermix, but instead restrict
      their growth to defined areas, thus forming two separate plexiform layers, the
      stratum opticum and the stratum album centrale. In this study we present
      experimental evidence indicating that the following three mechanisms might play a
      role in segregating both axonal populations: Retinal and tectobulbar axons differ
      in their ability to use the extracellular matrix protein laminin as a substrate
      for axonal elongation; the environment in the optic tectum is generally
      permissive for retinal axons, but is specifically nonpermissive for tectobulbar
      axons, resulting in a strong fasciculation of the latter; and growth cones of
      temporal retinal axons are reversibly inhibited in their motility by direct
      contact with the tectobulbar axon's membrane.

PMID- 1993125
TI  - Style and substance: further improvements.

PMID- 1993126
TI  - Direct measurement of skeletal muscle fatigue in patients with chronic heart
      failure.
AB  - Skeletal muscle function was measured as force production and fatigue in both the
      quadriceps (a large locomotive muscle) and adductor pollicis (a small intrinsic
      hand muscle) in five healthy volunteers, five patients with mild chronic heart
      failure, and five patients with severe chronic heart failure. The quadriceps of
      patients with chronic heart failure had a reduced muscle cross sectional area, a
      reduced maximum isometric force production, and an increased tendency to fatigue.
      Isometric force production and fatigue of the adductor pollicis, however, were
      not significantly different between the three groups under control conditions.
      But during circulatory occlusion fatigue in the adductor pollicis increased more
      in the patients with severe chronic heart failure. These differing findings in
      quadriceps and adductor pollicis suggest that skeletal muscle atrophy and reduced
      isometric force production are not a necessary consequence of chronic heart
      failure per se, because they were only present in the large locomotive muscle.
      The normal values for muscle fatigue observed in adductor pollicis in patients
      with chronic heart failure imply that skeletal muscle blood flow must increase
      normally during muscle activation when only a small muscle mass is used. These
      results are not compatible with the concept of a generalised impairment of normal
      vasodilatation within active skeletal muscle. In contrast, activation of a large
      muscle, such as quadriceps, results in the rapid onset of fatigue in patients
      with severe chronic heart failure. This fatigue may be related to the inability
      of the cardiovascular system to provide the required blood flow for the
      activation of a large muscle mass. The finding of a relatively greater increase
      in fatigue of adductor pollicis during circulatory occlusion in patients with
      severe chronic heart failure supports the hypnosis of an intrinsic abnormality of
      skeletal muscle in these patients.

PMID- 1993128
TI  - End diastolic flow velocity just beneath the aortic isthmus assessed by pulsed
      Doppler echocardiography: a new predictor of the aortic regurgitant fraction.
AB  - End diastolic flow velocity just beneath the aortic isthmus was measured within
      72 hours of cardiac catheterisation by pulsed Doppler echocardiography in 30
      controls and 61 patients with aortic regurgitation. The end diastolic flow
      velocity was determined at the peak R wave on a simultaneously recorded
      electrocardiogram. In all controls there was no reverse flow at the end diastole
      beneath the aortic isthmus. In patients with aortic regurgitation the end
      diastolic flow velocity correlated well with the angiographic grade of
      regurgitation (r = 0.81) and regurgitant fraction (r = 0.82). The mean (SD)
      values were 6.3 (5.2), 12.2 (4.3), 22.1 (5.7), and 34.3 (9.3) cm/s for patients
      with regurgitant fraction of less than 20%, between 20% and 40%, between 41% and
      60%, and greater than 60%, respectively. An end diastolic flow velocity of
      greater than 18 cm/s predicted a regurgitant fraction of greater than or equal to
      40% with a sensitivity of 88.5% and a specificity of 96%. The study suggests that
      the pulsed Doppler derived end diastolic flow velocity is a useful index in the
      routine non-invasive assessment of the severity of aortic regurgitation.

PMID- 1993127
TI  - Cardiac metabolism during exercise in healthy volunteers measured by 31P magnetic
      resonance spectroscopy.
AB  - A technique was devised for individuals to exercise prone in a magnet during
      magnetic resonance spectroscopy of the heart and phosphorus-31 magnetic resonance
      spectra of the heart were obtained by the phase modulated rotating frame imaging
      technique in six healthy volunteers during steady state dynamic quadriceps
      exercise. During prone exercise heart rate, blood pressure, and total body oxygen
      consumption were measured at increasing loads and the results were compared with
      those during Bruce protocol treadmill exercise. During prone exercise with a 5 kg
      load the heart rate was similar and the systolic and diastolic blood pressures
      were higher than those during stage 1 of the Bruce protocol. The rate-pressure
      products were similar but the total body oxygen consumption was lower during
      prone exercise. There was no difference in the ratio of phosphocreatine to
      adenosine triphosphate during rest and exercise.Thus during exercise that
      produced a local cardiac stress equal to or greater than that during stage 1 of
      the Bruce protocol treadmill exercise, the energy requirements of the normal
      human myocardium were adequately supplied by oxidative phosphorylation.

PMID- 1993129
TI  - Interatrial shunt flow profiles in newborn infants: a colour flow and pulsed
      Doppler echocardiographic study.
AB  - Interatrial shunt flow profiles in 36 normal term infants were examined serially
      by colour flow and pulsed Doppler echocardiographic techniques from within an
      hour of birth to four or five days after birth. Shunt flow across the foramen
      ovale was detected in 33 normal infants (92%) within an hour of birth (mean 40
      minutes). The occurrence of interatrial shunting decreased with age, but a shunt
      signal was still detected in 17 infants (47%) on the fourth or fifth day of life,
      by then the ductus arteriosus had already closed in all the normal infants. The
      direction of interatrial shunt flow was predominantly left-to-right, but in 64%
      there was a coexistent small right-to-left shunt in diastole within an hour of
      birth; by four to five days it was found in 19%. In the six patients with
      persistent fetal circulation the direction of the interatrial shunt flow was
      predominantly right-to-left with biphasic peaks in diastole and systole at the
      early stage of the disease, and the period of right-to-left shunt flow during
      each cardiac cycle was significantly longer than that in normal infants examined
      within 1 hour of birth. In all patients the ductus closed before the foramen
      ovale. At the time of ductal closure in all patients with persistent fetal
      circulation right-to-left shunt flow was seen during diastole and its period was
      still prolonged. These findings suggest that interatrial shunting, predominantly
      left-to-right, is common in normal newborn infants. Evaluation of the
      characteristics of the interatrial shunt by Doppler echocardiography may be
      useful for predicting the progress of or improvement in neonates with persistent
      fetal circulation.

PMID- 1993130
TI  - Lipomatous hypertrophy of the interatrial septum: an unusual intraoperative
      finding.
AB  - Lipomatous hypertrophy of the interatrial septum was an incidental finding in a
      man of 45 undergoing coronary artery bypass grafting for unstable angina. He was
      not overweight and did not have any rhythm disturbances. The diagnosis was made
      on frozen section.

PMID- 1993131
TI  - Prediction of outcome by prenatal Doppler analysis in a patient with aortic
      stenosis.
AB  - Stenosis of the aortic valve (pressure drop 50 mm Hg) was diagnosed prenatally by
      Doppler echocardiography in a 33 week old fetus. Measurement of time-velocity
      integrals through the tricuspid and mitral valves indicated a significantly
      higher flow in the right heart. The pressure drop across the aortic valve in the
      3 hour old infant was 80 mm Hg. The findings in this patient suggest that the
      usually accepted theory that prenatally the ventricles function in parallel
      should take into account the chronology of filling and ejection. In this patient
      the ability of a ventricle to generate a prenatal transvalvar pressure gradient
      was evidence that the size, compliance, and contractility of the ventricle were
      sufficient to maintain good function.

PMID- 1993132
TI  - Indications for cardiac transplantation.

PMID- 1993133
TI  - Holter monitoring of ventricular arrhythmias in a randomised, controlled study of
      intravenous streptokinase in acute myocardial infarction.
AB  - The occurrence of ventricular arrhythmias attributed to streptokinase treatment
      in acute myocardial infarction is not well defined. Holter monitoring was
      performed for 24 hours in 81 patients with suspected acute myocardial infarction
      randomised in a ratio of 2:1 to intravenous streptokinase 1.5 x 10(6) IU (n = 55)
      or placebo infusion (n = 26) 6.7 hours (mean) after the onset of symptoms. No
      episodes of ventricular fibrillation were recorded. For the whole 24 hour period
      and during the first three hours after the start of treatment the incidence and
      frequency of ventricular arrhythmias were similar in the patients randomised to
      streptokinase and to placebo. But when the results in patients randomised "early"
      after the onset of symptoms of suspected acute myocardial infarction were
      analysed separately the frequency of abnormal complexes, pairs, runs, and
      repetitive arrhythmias seemed to be higher in patients allocated to
      streptokinase. This may reflect arrhythmias associated with reperfusion.

PMID- 1993134
TI  - The urticarias 1990.

PMID- 1993135
TI  - Topical cyclosporin and T lymphocytes in keloid scars.

PMID- 1993136
TI  - Topical (1%) solution of griseofulvin in the treatment of tinea corporis.

PMID- 1993137
TI  - Very low dose acyclovir can be effective as prophylaxis for post-herpetic
      erythema multiforme.

PMID- 1993138
TI  - Immunopathological studies of Sweet's syndrome.

PMID- 1993139
TI  - Local anaesthesia with ethyl chloride freezing: problems despite proper
      application.

PMID- 1993140
TI  - Vascular involvement and toxoplasma infection.

PMID- 1993141
TI  - Physiology of the vellus hair follicle: hair growth and sebum excretion.
AB  - The growth of vellus hair and the secretion of sebum from vellus hair follicles
      were measured on the forehead, cheek, chest, shoulder and back of healthy men and
      women aged 15-30 years. Hair growth was assessed by computerized image-analysis
      of photographs and sebum excretion by the use of Sebutape followed by image
      analysis. The density of vellus hairs and the percentage of growing hairs were
      higher on the face than on the thorax (439 hairs/cm2 with 49% growing hairs on
      the forehead compared with 85 hairs/cm2 with 31.5% growing hairs on the back).
      The rate of growth ranged from 0.03 mm/day on the forehead to 0.13 mm/day on the
      back. The maximum length of vellus hair significantly decreased with age;
      otherwise hair growth was not affected by age or sex. Some variations in hair
      growth and sebum secretion were observed over a period of 3 months, but no
      consistent rhythms were detected. There was no obvious link between vellus hair
      growth and sebum excretion.

PMID- 1993142
TI  - Dermatology and the human gene map.
AB  - Chromosomal localization has been established for many genetic traits. Gene
      mapping may lead to the identification of disease genes, an understanding of
      pathogenesis, and the development of rational therapy, as well as facilitating
      antenatal diagnosis and genetic counselling. 'The new genetics' is therefore of
      great interest to the clinician. Unfortunately the complex technology and
      unfamiliar vocabulary of molecular biology often deter non-specialists from
      keeping abreast of these developments. This account explains the principles of
      gene mapping, discusses its relevance to dermatologists, and lists the
      established loci of dermatologically important genes.

PMID- 1993143
TI  - Allergic contact and photocontact dermatitis due to psoralens in patients with
      psoriasis treated with topical PUVA.
AB  - The incidence and clinical features of allergic contact and/or photocontact
      dermatitis due to psoralens were examined in 371 patients with psoriasis treated
      with topical PUVA. The psoralen derivatives used in the study were 8
      methoxypsoralen (8MOP), 3-carbethoxypsoralen (3CPs), 4,6,4'-trimethylangelicin
      (TMA) and 7-methyl pyridopsoralen (MPP). Of 371 patients treated with 8MOP, three
      (0.8%) developed an acute dermatitis in the PUVA-treated areas. This incidence
      was significantly lower (P less than 0.01) than that for 3CPs (four of 10
      patients) or that for TMA (six of 17 patients). None of the seven patients
      receiving MPP on PUVA had a reaction. It was confirmed that these dermatitis
      reactions were due to contact and/or photocontact allergy to psoralens by several
      methods that include patch and photopatch tests, photopatch test mapping,
      determination of the minimal erythema dose (MED) and immunohistochemistry.

PMID- 1993144
TI  - Cyclosporin A in atopic dermatitis: therapeutic response is dissociated from
      effects on allergic reactions.
AB  - Fourteen patients with severe chronic atopic dermatitis were treated with
      cyclosporin A (CyA, Sandimmun; 5 mg/kg/day) for 7-16 weeks. All showed a marked
      clinical improvement and half could omit topical corticosteroid treatment during
      therapy. Adverse effects were minor, but two patients relapsed despite continued
      treatment. In the others, the disease recurred soon after stopping CyA. Serum IgE
      levels and prick-test responses were unchanged by CyA. Immediate and late-phase
      cutaneous responses to intradermal house dust mite antigen (HDM) were
      significantly increased during treatment; but a delayed response, present at 24
      and 48 h, was unaffected. Four of six patients challenged with HDM patch tests to
      tape-stripped skin during treatment showed eczematous reactions at 48 h. Thus,
      cyclosporin A has a powerful therapeutic effect in atopic dermatitis but does not
      reduce allergic responses to inhalant antigens.

PMID- 1993145
TI  - 'High single-dose' European PUVA regimen also causes an excess of non-melanoma
      skin cancer.
AB  - We report the results of a long-term (12.8 years) follow-up study of the
      detection of malignant and benign skin tumours in patients with psoriasis, who
      were treated with PUVA according to the European, 'high single-dose' regimen. A
      total of 13 squamous cell carcinomas (SCC) and 24 basal cell carcinomas (BCC)
      were diagnosed in 11 of 260 patients. The incidence of both SCC and BCC was
      increased in comparison with the general Dutch population. The ratio of SCC to
      BCC in the general population was 1:8 but was 1:2.5 in our study group. A
      positive correlation was observed between the development of SCC and the total
      UVA dosage, the age of the patient at the start of the PUVA treatment and a
      history of arsenic use. This dose-related increase in the incidence of SCC,
      reported in studies from the U.S.A., has not been found in earlier European
      studies. The average time period between the start of PUVA therapy and the
      diagnosis of the first malignant skin tumour was 6.0 years for SCC and 4.7 years
      for BCC. Among the 49 benign skin tumours were actinic keratoses, a
      keratoacanthoma and 'PUVA keratoses', a newly described hyperkeratotic lesion,
      especially found in PUVA-treated patients.

PMID- 1993147
TI  - Induction of lesions of dermatitis herpetiformis by autologous serum.
AB  - In the present study various factors which contribute to the initiation of
      lesions in dermatitis herpetiformis (DH) were examined. Thirty-one patients with
      DH, seven with bullous pemphigoid, two with linear IgA disease and two healthy
      subjects were studied either before starting treatment or after stopping dapsone
      for up to 5 days. Intradermal inoculation of freshly prepared autologous serum
      was followed after 18-24 h by the formation of DH-like lesions in 24/31 DH
      patients. The lesions were erythematous papules, often with vesicles and
      microscopically showed papillary tip microabscesses. Serum-induced formation of
      lesions only occurred in patients with active DH with some spontaneous lesion
      formation: it did not occur in any of the non-DH controls. The formation of
      lesions was dose-related, declining proportionately with dilution of the serum
      down to 1/16. Plasma prepared by various methods of anticoagulation (heparin,
      citrate, EDTA) caused lesser reactions, while addition of heparin or epsilon
      amino caproic acid (EACA), but not citrate, to serum substantially inhibited the
      formation of lesions. This suggested the responsible factor might be a protease.
      Other vasoactive agents including histamine (1-4 micrograms) and compound 48/80
      (1-5 micrograms) caused normal immediate wealing. DH-like lesions occurred in
      only one of 13 subjects challenged with histamine and two of nine challenged with
      48/80. In all these, autologous serum elicited large vesicular responses. There
      is a factor(s) in serum in DH which can initiate the formation of lesions. This
      factor appears to be activated by clotting and can be inhibited by heparin and
      EACA, suggesting it may be a protease.

PMID- 1993146
TI  - Selective cytotoxicity of N-acetyl-4-S-cysteaminylphenol on follicular
      melanocytes of black mice.
AB  - Previous in vivo studies have shown that 4-S-cysteaminylphenol (4-S-CAP) and N
      acetyl-4-S-cysteaminylphenol (N-Ac-4-S-CAP) have antimelanoma effects and that N
      Ac-4-S-CAP produced a 98% depigmentation of hair follicles of black mice. This
      study investigated the process of selective melanocytotoxicity by N-Ac-4-S-CAP
      through light and electron microscopy studies of hair follicles obtained from
      newborn black mice treated with N-Ac-4-S-CAP. Visible changes in follicular
      melanocytes were found 4 h after intraperitoneal (i.p.) administration. Clumps of
      melanin granules and areas of melanocytic nuclear condensation were seen in the
      hair follicles. On electron microscopy there was progressive destruction of
      melanocytes with swelling of membranous organelles, nuclear condensation, and
      vacuolation of the cytoplasm, culminating in completely necrotic cells. None of
      these changes were demonstrated in the surrounding keratinocytes. N-Ac-4-S-CAP
      appears to have specific, cytotoxic effects on melanocytes actively producing
      eumelanin. The drug may not affect precursor or dormant melanocytes which retain
      the ability to become active, melanin-producing cells.

PMID- 1993148
TI  - An adult with common acute lymphoblastic leukaemia (C-ALL) presenting with skin
      infiltration.
AB  - A 22-year-old man presented with multiple raised erythematous skin lesions,
      pyrexia and epistaxis. A diagnosis of common acute lymphoblastic leukaemia (C
      ALL) was made by morphological, cytochemical, immunological and cytogenetic
      examination of peripheral blood and bone marrow. Biopsy of the skin revealed
      leukaemic infiltration by similar cells.

PMID- 1993149
TI  - Unilateral naevoid telangiectasia syndrome associated with metastatic carcinoid
      tumour.

PMID- 1993151
TI  - Benign persistent papular acantholytic and dyskeratotic eruption: a case report
      and review of the literature.
AB  - We report a case of a 35-year-old female with a persistent pruritic acantholytic
      and dyskeratotic eruption on the chest and vulva. The light and electron
      microscopic studies showed suprabasal epidermal clefting with acantholysis and
      dyskeratotic cells. We suggest that the most appropriate term for this case is
      that of benign persistent papular acantholytic and dyskeratotic eruption.

PMID- 1993150
TI  - Erythema elevatum diutinum mimicking porphyria cutanea tarda.
AB  - A case of erythema elevatum diutinum (EED) closely resembling porphyria cutanea
      tarda (PCT) is reported. The initial skin biopsies were suggestive for PCT but
      porphyrin levels in the urine, stool and plasma were normal. A further biopsy
      from an early cutaneous lesion showed a leucocytoclastic vasculitis with
      fibrinoid necrosis of the vessel walls.

PMID- 1993152
TI  - Acquired dermal melanocytosis of the face and extremities.
AB  - Four cases of dermal melanocytosis with symmetrical areas of hyperpigmentation
      involving the face and extremities are reported. Light and electron microscopic
      studies showed changes similar to those seen in naevus of Ota.

PMID- 1993153
TI  - A critical review of the effect of factory closures on health.
AB  - The dramatic rise in unemployment in the 1970s and 1980s has led to an increase
      in research into the possible effects of unemployment on health. Studies of the
      effects of job loss are difficult to interpret because of the difficulty in
      ruling out selection effects--for example, the least fit may be more likely to be
      made redundant. The study of factory closures is appealing since all employees
      are made redundant and all the studies of factory closure recorded in the Index
      Medicus since 1980 are reviewed. None of the studies fulfil all the criteria for
      an ideal study, and most fail on several counts. The small sample sizes are often
      unavoidable, but the lack of awareness of possible selection effects often
      results in a biased control group of only those people who are economically
      active. Also, the short duration of follow up restricts the detection of possible
      long term effects on health. Thus the conclusions that can be drawn about the
      health effects of factory closures are limited. Whereas there is evidence of
      short term effects on mental health and of increased use of primary health care,
      no long term effects have been studied and objective data on physical health are
      almost non-existent.

PMID- 1993154
TI  - An electrophysiological follow up of patients with n-hexane polyneuropathy.
AB  - Electroneurographic (ENeG) and evoked potential (EP) studies were regularly
      performed on 11 printing workers with n-hexane polyneuropathy after cessation of
      exposure. At the initial examination, the ENeG studies simulated a demyelinative
      process. Further slowing of nerve conduction velocity, or further decreasing of
      action potential amplitude, or both in the follow up ENeG study were found in
      about half the patients. The motor distal latency did not worsen. Nerve
      conduction returned to normal earlier in the sensory than in the motor nerves.
      After the patients had regained full motor capability, conduction velocities in
      motor nerves were still significantly slowed. These ENeG characteristics
      correlate with the pathological and pathophysiological changes in experimental
      hexa-carbon neuropathies. The initial findings from the EP studies indicated a
      conduction abnormality in the central nervous system (CNS). Delayed worsening
      occurred in the amplitude of visual EPs in three patients. On serial follow up,
      the interpeak latency and interpeak amplitude of visual EPs improved little.
      Residual abnormalities were also found in the interpeak latency of auditory EPs
      in the brainstem and in the absolute latency of scalp somatosensory EPs from the
      peroneal nerve. Astroglial proliferation in the CNS probably impedes recovery of
      the abnormalities in EP.

PMID- 1993155
TI  - Exposure to organic solvents and neuropsychological dysfunction: a study on
      monozygotic twins.
AB  - Twenty one monozygotic twins exposed to organic solvents were compared with their
      non-exposed cotwins by performance in psychological tests. A further 28
      monozygotic twin pairs were examined as a reference group. The study used 11
      tests, 10 of which had shown an effect in previous studies on the results of
      exposure to solvents. Paired comparisons of the test scores showed the exposed
      twins to have lower performance in associative learning, digit span, and block
      design. These results agree with two previous studies that used a similar set of
      tests. Contrary to some other studies, psychomotor speed was not affected, but
      the results indicated a marginal effect on the control of hand movements. Further
      comparison of subgroups with a low and a high exposure showed the prevalence of
      subtle neuropsychological dysfunction to be greater among the more exposed twins.

PMID- 1993156
TI  - Visual disturbances in man as a result of experimental and occupational exposure
      to dimethylethylamine.
AB  - Experimental exposure of four volunteers to 40-50 mg/m3 of dimethylethylamine
      (DMEA) for eight hours caused irritation of the mucous membrane of their eyes,
      subjective visual disturbances (haze), and slight oedema of the corneal
      epithelium. The thickness of the cornea showed a slight but consistent increase
      in all four subjects at these exposures and in two subjects exposed to 10 mg/m3.
      Concentrations of 80 and 160 mg/m3 for 15 minutes caused eye irritation but no
      visual disturbances or corneal oedema. Occupational exposure for eight hours to
      about 25 mg/m3 of DMEA (with peaks above 100 mg/m3) was also associated with eye
      irritation, haze, and corneal oedema. The divergence between our findings and
      other reports in which visual disturbances occurred at lower concentrations
      during occupational exposure may be due to peak concentrations.

PMID- 1993157
TI  - The effect of smoking on the development of allergic disease and specific
      immunological responses in a factory workforce exposed to humidifier
      contaminants.
AB  - The effects of smoking on the development of work related asthma and on the
      production of specific IgE and IgG antibodies to antigen from a contaminated
      humidifier are described for a sample of 258 workers from a printing factory.
      Current smoking was associated with low production of IgG antibody but with
      higher production of IgE antibody. No dose response for either antibody was found
      when numbers of cigarettes or pack-years smoked were considered. Work related
      asthma was detected in 12 workers by peak flow recordings. Six were current
      smokers and one was an ex-smoker. One subject with work related asthma had a high
      (and one a marginal) concentration of specific IgE to humidifier antigen.

PMID- 1993158
TI  - Ventilatory function after exposure to various respirable hazards in a population
      of former coal miners.
AB  - The ventilatory function of 406 male former coal miners who had presented at the
      Cook County Hospital occupational medicine clinic between January 1976 and April
      1987 was studied to determine whether subsequent exposure to respiratory hazards
      after leaving the coal mines adversely affected lung function. The miners were
      divided into five exposure groups based on their exposure to respirable hazards.
      These were coal dust only, coal dust plus asbestos dust, coal dust plus silica
      dust, coal dust plus another respirable hazard and coal dust plus two other
      respirable dust exposures. Duration of employment in coal mines, race, smoking
      history, and mean age were not significantly different between the various
      exposure groups. No significant difference was found in the per cent of predicted
      forced expiratory volume in one second (FEV1), per cent of predicted forced vital
      capacity (FVC), and FEV1/FVC when the coal dust only group was compared with each
      of the other four exposure groups using ANOVA. Among former coal miners who
      present for a respiratory disability determination, therefore, exposure to
      respirable hazards subsequent to employment in coal mines is not associated with
      a statistically significant deterioration in ventilatory function.

PMID- 1993159
TI  - Biophysical alteration of lung surfactant by extracts of cotton dust.
AB  - Byssinosis, a lung disease that can affect cotton mill workers, may be caused in
      part by lipopolysaccharides (LPS) from Gram negative bacteria. In vitro, LPS
      complexes with sheep lung surfactant (SLS). To determine whether LPS in extracts
      of cotton dust alters the biophysical characteristics of lung surfactant, aqueous
      extracts (1.0% w:v) of sterile surgical cotton (SSC) and a bulk raw cotton dust
      (1182DB) were prepared. Aliquots of the soluble extracts were incubated with SLS
      and studied by sucrose gradient centrifugation, surface tension analysis, and
      high pressure liquid chromatography (HPLC). The chromatography was employed to
      analyse for 3-hydroxymyristate (3-HM), a fatty acid indicating LPS. Also,
      purified Enterobacter agglomerans LPS and 3-HM as controls and as mixtures with
      SLS, were studied by HPLC. Sucrose gradient centrifugation showed that SLS-SSC,
      SLS-1182DB, and the SLS control had similar densities that differed from the
      remaining controls. The SLS-1182DB exhibited a floccule absent in the other
      samples. Surface tension values of SLS-SSC and SLS-1182DB differed significantly
      from all controls but only slightly from one another. 3-Hydroxymyristate was
      detected by HPLC in the 3-HM control, EA-LPS, SLS-EA-LPS, and SLS-1182DB, but not
      in SLS-SSC or the remaining controls. Apparently, 3-HM was below the HPLC
      detection range in SSC. The data indicate that LPS in the 1182DB, SSC and EA-LPS
      samples complexed with SLS. Floccule development in SLS-1182DB but not in SLS-EA
      LPS suggests a further component(s) present in the bulk raw cotton dust, as well
      as LPS, which complexes with SLS. The data suggest that biophysical alterations
      to lung surfactant may play a part in the pathogenesis of byssinosis.

PMID- 1993160
TI  - Occupational exposure to asbestos as evaluated from work histories and analysis
      of lung tissues from patients with mesothelioma.
AB  - The past occupational exposure to asbestos of 23 patients with mesothelioma (21
      men and two women) has been evaluated by a personal interview of their work
      history and by determination of the fibre burden in their lung tissue with
      scanning electron microscopy (SEM) and x ray microanalysis. According to the work
      history, nine patients (39%) had definitely been or probably been exposed to
      asbestos, six patients (26%) had had possible exposures, and eight patients (35%)
      unlikely or unknown exposure to asbestos. The two female patients were in the
      unknown exposure category. The fibre concentrations in the patients' lung tissue
      ranged from less than 0.1 million to 370 million fibres (f) per g dry tissue.
      Concentrations of over one million f per g dry tissue were found in 15 patients
      (65%). The lung fibre concentrations of all nine male office workers analysed for
      reference were less than one million f per g dry tissue. Seventy eight per cent
      of the patients with mesothelioma had at least possible exposure according to
      their history of work or concentrations of more than one million f per g dry
      tissue.

PMID- 1993162
TI  - Sedentary work in middle life and fracture of the proximal femur.

PMID- 1993161
TI  - Persistent biological reactivity of quartz in the lung: raised protease burden
      compared with a non-pathogenic mineral dust and microbial particles.
AB  - This study assessed the potential harmfulness of particles in the lung by
      measuring their ability to elicit and maintain an inflammatory response and to
      damage lung tissue. It compared the inflammogenicity of two nondurable,
      biological particulates (Corynebacterium parvum and zymosan) with a pathogenic
      mineral dust (quartz) and a nonpathogenic dust (titanium dioxide) by dosing rats
      via the intratracheal route and measuring the consequent alveolitis. The
      magnitude and duration of the inflammatory response were assessed by measuring
      the total number of leucocytes and the percentage of neutrophils obtained by
      bronchoalveolar lavage. Two key functional parameters of the lavaged leucocytes-
      ability to degrade fibronectin and production of plasminogen activator--were also
      measured. A marked inflammatory response had occurred by one day after
      instillation, characterised by increases in total leucocyte numbers and
      percentage of neutrophils in the bronchoalveolar lavages, with all four test
      materials. In all but the quartz exposed animals, the inflammation subsided
      rapidly thereafter, approaching control levels by 15 days after injection; in the
      quartz exposed animals the alveolitis persisted for up to 30 days. All of the
      inflammogens generated chemotaxins in rat serum in vitro and so, by analogy,
      might also be expected to generate chemotactic activity in alveolar lining fluid
      which could contribute to the generation of an inflammatory response. The
      cellular inflammatory response was accompanied by a concomitant increase in the
      proteolytic activity of the bronchoalveolar lavage leucocytes but production of
      plasminogen activator remained unchanged. In vitro exposure to the inflammogens
      had no effect on the proteolytic activity against fibronectin or on the
      plasminogen activator activity of bronchoalveolar leucocytes.

PMID- 1993163
TI  - Malignant melanomas of the nasal cavity after occupational exposure to
      formaldehyde.
AB  - Formaldehyde is a well known nasal carcinogen in rodents, but so far there has
      been no convincing evidence that workers occupationally exposed to formaldehyde
      have an increased risk of nasal cancer. In this study three cases of malignant
      melanoma of the nasal mucosa in persons occupationally exposed to formaldehyde
      for a long time are presented. The occurrence of such a rare tumour in patients
      with significant exposure to a known carcinogen warrants further investigation.

PMID- 1993164
TI  - Characteristics of a 95-kDa matrix metalloproteinase produced by mammary
      carcinoma cells.
AB  - A Mr 95,000 matrix metalloproteinase (MMP) produced by rat mammary carcinoma
      cells has been isolated and characterized. The MMP was secreted in a
      proteolytically inactive form that was free from bound tissue inhibitor of
      metalloproteinases. The enzyme was highly glycosylated as evident from an
      apparent drop of Mr from 95,000 to 83,000 after treatment with N-glycanase.
      Rotary shadowing electron micrographs of purified proenzyme preparations revealed
      a uniform set of ellipsoidal molecules. Treatment of the proenzyme with 1% SDS
      resulted in generation of catalytic activity and exposed a cryptic unpaired Cys
      residue. The latent proenzyme may be activated in at least three additional ways:
      either spontaneously upon storage, by treatment with organomercurials, or by
      limited proteolysis by trypsin. Each mode of activation yielded a distinct
      pattern of cleavage of the enzyme. The activated enzyme cleaved gelatin
      (denatured type I collagen) and native type IV and V collagen at 30-37 degrees C.
      Noncollagenous proteins including alpha 1-proteinase inhibitor, casein, and
      fibrinogen also were cleaved. The rat mammary carcinoma cell line that produces
      the Mr 95,000 MMP is composed of two distinct (epithelial- and myoepithelial
      like) cell types. The enzyme is expressed constitutively by the epithelial cells.
      This suggests that expression of the Mr 95,000 MMP is regulated differently from
      that of interstitial collagenase, which is produced by the epithelial cells only
      in response to specific inductive factor(s) from the myoepithelial-like cells.
      Monoclonal antibodies raised against the purified latent Mr 95,000 form of the
      enzyme bind specifically to the Mr 95,000 MMP and have been used to localize the
      enzyme to the Golgi region and cytoplasmic granules of the epithelial cells.

PMID- 1993165
TI  - Conformation of NADP+ bound to a type II dihydrofolate reductase.
AB  - Type II dihydrofolate reductases (DHFRs) encoded by the R67 and R388 plasmids are
      sequence and structurally different from known chromosomal DHFRs. These plasmid
      derived DHFRs are responsible for confering trimethoprim resistance to the host
      strain. A derivative of R388 DHFR, RBG200, has been cloned and its physical
      properties have been characterized. This enzyme has been shown to transfer the
      pro-R hydrogen of NADPH to its substrate, dihydrofolate, making it a member of
      the A-stereospecific class of dehydrogenases [Brito, R. M. M., Reddick, R.,
      Bennett, G. N., Rudolph, F. B., & Rosevear, P. R. (1990) Biochemistry 29,9825].
      Two distinct binary RBG200.NADP+ complexes were detected. Addition of NADP+ to
      RBG200 DHFR results in formation of an initial binary complex, conformation I,
      which slowly interconverts to a second more stable binary complex, conformation
      II. The binding of NADP+ to RBG200 DHFR in the second binary complex was found to
      be weak, KD = 1.9 +/- 0.4 mM. Transferred NOEs were used to determine the
      conformation of NADP+ bound to RBG200 DHFR. The initial slope of the NOE buildup
      curves, measured from the intensity of the cross-peaks as a function of the
      mixing time in NOESY spectra, allowed interproton distances on enzyme-bound NADP+
      to be estimated. The experimentally measured distances were used to define upper
      and lower bound distance constraints between proton pairs in distance geometry
      calculations. All NADP+ structures consistent with the experimental distance
      bounds were found to have a syn conformation about the nicotinamide-ribose (X =
      94 +/- 26 degrees) and an anti conformation about the adenine-ribose (X = -92 +/-
      32 degrees) glycosidic bonds.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1993166
TI  - Impact on catalysis of secondary structural manipulation of the alpha C-helix of
      Escherichia coli dihydrofolate reductase.
AB  - The alpha C-helix of Escherichia coli dihydrofolate reductase has been converted
      to its counterpart in Lactobacillus casei by a triple mutation in the helix
      (H45R, W47Y, and I50F). These changes result in a 2-fold increase in the steady
      state reaction rate (kcat = 26 s-1) that is limited by an increased off rate for
      the release of tetrahydrofolate (koff = 40 s-1 versus 12 s-1). On the other hand
      the mutant protein exhibits a 10-fold increase in the KM value (6.8 microM) for
      dihydrofolate and a 10-fold decrease in the rate of hydride transfer (85 s-1)
      from NADPH to dihydrofolate. The elevated rate of tetrahydrofolate release upon
      the rebinding of NADPH, a characteristic of the wild-type enzyme-catalyzed
      reaction, is diminished. The intrinsic pKa (6.4) of the mutant enzyme binary
      complex with NADPH is similar to that of the wild type, but the pKa of the
      ternary complex is increased to 7.3, about on pH unit higher than the wild-type
      value. Further mutagenesis (G51P and an insertion of K52) was conducted to
      incorporate a hairpin turn unique to the C-terminus of the alpha C-helix of the
      L. casei enzyme in order to adjust a possible dislocation of the new helix. The
      resultant pentamutant enzyme shows restoration of many of the kinetic parameters,
      such as kcat (12 s-1), KM (1.1 microM for dihydrofolate), and khyd (526 s-1), to
      the wild-type values. The synergism in the product release is also largely
      restored. A substrate-induced conformational change responsible for the fine
      tuning of the catalytic process was found to be associated with the newly
      installed hairpin structure. The Asp27 residue of the mutant enzyme was found to
      be reprotonated before tetrahydrofolate release.

PMID- 1993167
TI  - Ligand binding studies of engineered cytochrome P-450d wild type, proximal
      mutants, and distal mutants.
AB  - Interactions of various axial ligands with cytochrome P-450d wild type, proximal
      mutants (Lys453Glu, Ile460Ser), and putative distal mutants (Glu318Asp,
      Thr319Ala, Thr322Ala) expressed in yeast were studied with optical absorption
      spectroscopy. P-450d wild type and all five mutants were purified essentially as
      the high-spin form, but the putative distal mutants contained about 5% low-spin
      form. Bindings of metyrapone and 4-phenylimidazole to the wild type and all
      mutants formed nitrogen-bound low-spin forms. In contrast, binding of 2
      phenylimidazole to the wild type and most of mutants formed oxygen-bond low-spin
      forms except for the mutant Glu318Asp in which the nitrogen-bound low-spin form
      was formed. By analogy with the distal structure of P-450cam, it was thus
      suggested that Glu318 of P-450d, which corresponds with Asp251 of P-450cam,
      somehow interacts with 2-phenylimidazole over the heme plane. Addition of 1
      butanol and acetanilide, a substrate of P-450d, to the wild type and mutants
      caused the spin change to the low-spin form. The order of dissociation constants
      of these oxygen ligands to P-450d was wild type greater than proximal mutants
      greater than putative distal mutants. Spectral analyses showed that the binding
      of acetanilide is the same as that of another substrate, 7-ethoxycoumarin, in the
      putative distal mutants but is not the same in the wild type and proximal
      mutants. From these findings together with other spectral data, it was suggested
      that the region from Glu318 to Thr322 is located at the distal region of the heme
      in membrane-bound P-450d as suggested from the X-ray crystal structure of water
      soluble P-450cam and amino acid alignments of P-450s.

PMID- 1993168
TI  - Phosphorylation and formation of hybrid enzyme species test the "half of sites"
      reactivity of Escherichia coli succinyl-CoA synthetase.
AB  - Recent sequencing experiments have identified alpha-His246 as the phosphorylation
      site of Escherichia coli succinyl-CoA synthetase [Buck, D., Spencer, M. E., &
      Guest, J. R. (1985) Biochemistry 24, 6245-6252]. We have replaced alpha-His246
      with an asparagine residue using site-directed mutagenesis techniques. The
      resulting mutant enzyme (designated H246N) exhibited no enzyme activity, as
      expected, but was found as a structurally intact, stable tetramer. Small
      differences in the net charge of H246N and wild-type enzymes were first detected
      on native polyacrylamide gels. These charge differences were resolved by using
      native isoelectric focusing gels to further separate the wild-type enzyme into
      diphosphorylated, monophosphorylated, and unphosphorylated species. The enzyme
      species were found to be interconvertible upon incubation with the appropriate
      enzyme substrate(s). Sample mixtures containing increasing molar ratios of H246N
      (alpha H246N beta)2 to wild-type enzyme (alpha beta)2 were unfolded and then
      refolded. The refolded enzyme mixtures were analyzed for enzymatic activity and
      separated on native isoelectric focusing gels. The hybrid enzyme (alpha beta
      alpha H246N beta) retained a significant amount of enzyme activity and also
      exhibited substrate synergism (stimulation of succinate in equilibrium succinyl
      CoA exchange in the presence of ATP). Substrate synergism with this enzyme has
      been interpreted as evidence for interaction between active sites in such a way
      that only a single phosphoryl group is covalently attached to the enzyme at a
      given time [Wolodko, W. T., Brownie, E.R., O'Connor, M. D., & Bridger, W. A.
      (1983) J. Biol. Chem. 258, 14116-14119]. On the contrary, we conclude that
      tetrameric succinyl-CoA synthetase from E. coli is comprised of two independently
      active dimer molecules associated together to form a "dimer of dimers" that
      displays substrate synergism within each dimer and not necessarily between
      dimers.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1993169
TI  - 5'-Nucleotidase I from rabbit heart.
AB  - 5'-Nucleotidase I (N-I) from rabbit heart was purified to homogeneity. After
      ammonium sulfate precipitation, the purification involved chromatography on
      phosphocellulose, DEAE-Sepharose, AMP-agarose, and ADP-agarose. The pure enzyme
      has a specific activity of 318 mumol (mg of protein)-1 min-1. Polyacrylamide gel
      electrophoresis in the presence of sodium dodecyl sulfate yields a subunit
      molecular weight of 40,000. N-I is activated by ADP but not by ATP, in contrast
      to the 5'-nucleotidase (N-II) purified by Itoh et al. (1986), which is activated
      by ATP and, less well, by ADP. N-I displays sigmoidal saturation kinetics in the
      absence of ADP and hyperbolic kinetics in the presence of ADP. Partially purified
      N-I was previously shown to prefer AMP over IMP as substrate (Truong et al.,
      1988); this has been confirmed for pure N-I. Comparison of AMP and ADP
      concentrations reported to occur in heart with the kinetic behavior of N-I
      implicates N-I as the enzyme responsible for producing adenosine under conditions
      leading to a rise in ADP and AMP, such as hypoxia or increased workload. N-I is
      not activated by the ADP analogue adenosine 5'-methylenediphosphonate (AOPCP) and
      is only weakly inhibited by relatively high concentrations of AOPCP, in contrast
      to 5'-nucleotidase from plasma membrane, which is powerfully inhibited by this
      analogue. N-I shows an absolute dependence on Mg2+ ions. Mn2+ and Co2+ ions can
      replace Mg2+ ions as activator; Ni2+ and Fe2+ are much less effective, while
      Ca2+, Ba2+, Zn2+, and Cu2+ fail to activate the enzyme.

PMID- 1993170
TI  - Isolation and characterization of somatolactin, a new protein related to growth
      hormone and prolactin from Atlantic cod (Gadus morhua) pituitary glands.
AB  - The characterization of cod somatolactin (SL), a new pituitary protein belonging
      to the growth hormone/prolactin family, is described. Cod SL has a molecular
      weight of 26 kDa and consists of 209 amino acids, of which eight are Cys. The
      protein has three disulfide bonds between residues Cys5-Cys15, Cys65-Cys181, and
      Cys198-Cys206. The Cys residues at positions 42 and 180 are not involved in
      disulfide bonding. The positions of these disulfide bonds are homologous to those
      found in prolactin and growth hormone. Cod SL has two possible N-glycosylation
      sites, but only one appears to have carbohydrate units attached. Chemical
      analysis showed the following sugars to be present: galactose, mannose, N
      acetylneuramic acid, and glucosamine. A smaller variant (23 kDa) of SL has been
      isolated, which is believed to be deglycosylated. Sequence comparison revealed
      cod SL to be similarly related to both GH and PRL, but slightly higher identity
      was observed to the tetrapod hormones (27-33%) than to the teleost hormones (21
      27%).

PMID- 1993171
TI  - Disulfide assignments in recombinant mouse and human interleukin 4.
AB  - The disulfide pairings of mouse and human interleukin 4 (IL-4) proteins have been
      determined. The purified proteins, synthesized by recombinant DNA technology, are
      fully active as judged by their ability to stimulate an appropriate biological
      response in a variety of functional assays. Peptide maps were produced by
      digesting the proteins with pepsin and separating the resulting fragments by
      reverse-phase HPLC using linear acetonitrile-TFA gradients. Cystine-containing
      peptides were identified by determining which reverse-phase peaks showed an
      altered elution pattern after reduction. These peptides were purified further and
      defined by composition and sequence analysis. Three sets of disulfide-linked
      peptides were consistently identified for each protein. For mouse IL-4, the first
      and fifth, second and fourth, and third and sixth cysteines are joined. The
      disulfide bonds in human IL-4 are between the first and sixth, second and fourth,
      and third and fifth cysteines. A large double-loop region within the central
      three-fifths of each protein is stabilized by these bonds. Sequence analysis of
      the peptides containing the third and fifth cysteines of human IL-4 also
      demonstrated that only one of the potential N-glycosylation sites is used by C127
      mammary tumor cells. Complete alkylation of mouse IL-4 under mild conditions
      completely destroyed its biological activity in a hematopoietic precursor cell
      proliferation assay.

PMID- 1993172
TI  - Interaction of fibronectin with heparin in model extracellular matrices: role of
      arginine residues and sulfate groups.
AB  - The interaction of heparin with the NH2-terminal domain of human plasma
      fibronectin was studied by using matrix-driven translocation, an assay for the
      adhesion of extracellular macromolecules with cell or particle surfaces within
      artificial collagen matrices. Partial desulfation of heparin rendered it
      ineffective in competitively inhibiting the interaction of the fibronectin NH2
      terminal domain with heparin-coated particles, suggesting a role for sulfate
      groups of heparin in the interaction. Analysis of the fibronectin domain in terms
      of its primary structure, its proposed organization into "type I modules", and
      its hydrophilic and flexible segments led to the identification of several
      arginine-containing sites of potential interaction with the sulfate groups of
      heparin. Modification of increasing numbers of arginine side chains with 1,2
      cyclohexanedione under mild conditions eventually led to decreases in
      translocation-promoting activity, and of heparin binding capacity as measured in
      a gel-shift assay, but the major portions of these functions were retained even
      when the four most accessible arginines (attributed to sites in and adjacent to
      the large loops of the type I modules) were modified. With the modification of
      additional arginines (attributed to sites in the small loops), both functions
      were lost. The peptide Gly-Arg-Gly, corresponding to a repeated determinant at
      the tips of two small loops, inhibited translocation, but arginine alone did not.
      Cleavage of the large loops by CNBr also led to loss of translocation-promoting
      activity. The correspondence between the molecular determinants of matrix-driven
      translocation and those previously found for mesenchymal morphogenesis indicates
      the utility of this system in the analysis of adhesive interactions of biological
      importance.

PMID- 1993173
TI  - Intron-exon organization of the human gene coding for the lipoprotein-associated
      coagulation inhibitor: the factor Xa dependent inhibitor of the extrinsic pathway
      of coagulation.
AB  - Blood coagulation can be initiated when factor VII(a) binds to its cofactor
      tissue factor. This factor VIIa/tissue factor complex proteolytically activates
      factors IX and X, which eventually leads to the formation of a fibrin clot.
      Plasma contains a lipoprotein-associated coagulation inhibitor (LACI) which
      inhibits factor Xa directly and, in a Xa-dependent manner, also inhibits the
      factor VIIa/tissue factor complex. Here we report the cloning of the human LACI
      gene and the elucidation of its intron-exon organization. The LACI gene, which
      spans about 70 kb, consists of nine exons separated by eight introns. As has been
      found for other Kunitz-type protease inhibitors, the domain structure of human
      LACI is reflected in the intron-exon organization of the gene. The 5' terminus of
      the LACI mRNA has been determined by primer extension and S1 nuclease mapping.
      The putative promoter was examined and found to contain two consensus sequences
      for AP-1 binding and one for NF-1 binding, but no TATA consensus promoter
      element.

PMID- 1993174
TI  - Influence of the local amino acid sequence upon the zones of the torsional angles
      phi and psi adopted by residues in proteins.
AB  - A set of parameters is derived to express the influence of the local amino acid
      sequence on the torsional angles phi and psi adopted by each residue in a
      protein. The formalism used, which is based on information theory, evaluates the
      probability for a given residue to be in a particular zone of the Ramachandran
      map. Comparisons with crystallographic structures suggest that the method can
      extract almost all of the available information from the local sequence and show
      that the local sequence carries only, on average, about 65% of the information
      necessary for specifying the conformation of a given residue in a protein. The
      rest is specified by long-range interactions that are specific for each protein
      fold. The parameters derived here provide a more detailed description of the
      prediction than other methods in allowing the allocation of the torsional angles
      for residues having an aperiodic structure and are intended to be used for
      directing the conformational search in a subsequent simulation of the three
      dimensional structure. This method should also predict segments of the
      polypeptide chain that are the most stable and thus less sensitive to long-range
      interactions.

PMID- 1993175
TI  - Effect of amino acid ion pairs on peptide helicity.
AB  - The three ER ion pairs in the peptide acetyl-W(EAAAR)3A-amide were replaced in
      turn with the ion pairs EK, EO, DR, DK, and DO, where O represents an ornithine
      residue. The far-ultraviolet circular dichroic spectra of the six peptides
      measured in 10 mM NaCl at pH 2 and 0 degrees C form a nested set having an
      isodichroic point at 203 nm of -17,000 deg cm2 dmol-1. The ellipticity values of
      the six peptides at 222 nm range from -31,600 to -7400 deg cm2 dmol-1 in the
      order listed. Changing the pH of each peptide solution from 2 to 13 also
      generates a nested set of dichroic spectra with the same isodichroic values.
      Increasing the pH from 2 to 7 differentially increases the ellipticity at 222 nm
      in a single transition having an apparent pK of 4.1 for the E-containing peptides
      are 3.6 for the D-containing peptides. Increasing the pH beyond neutrality
      differentially decreases the ellipticity at 222 nm in a single transition having
      an apparent pK of greater than or equal to 13.2 for the R-containing peptides,
      11.1 for the K-containing peptides, and 10.7 for the O-containing peptides. It is
      proposed that the difference in the ellipticity of the six peptides chiefly
      reflects the helix preferences for the variable residues supplemented by
      intrahelical electrostatic interactions in the neutral pH range.

PMID- 1993176
TI  - Oligomeric protein associations: transition from stochastic to deterministic
      equilibrium.
AB  - Transfer of electronic excitation energy (sensitized fluorescence) between donor
      and acceptor fluorophores separately attached to dimer or tetramer proteins is
      used to demonstrate the exchange of subunits among the undissociated particles.
      In dimers subjected to a pressure that produces half-dissociation, the exchange
      occurs at a rate that approaches the rate of dissociation. In the tetramers of
      glyceraldehydephosphate dehydrogenase and lactate dehydrogenase at 0 degrees C,
      the times for subunit exchange are nearly 2 orders of magnitude, and at room
      temperature 5-10 times longer than the time required to reach the dissociation
      equilibrium. By application of a novel method, pressure is shown to
      preferentially increase the rate of dissociation in dimers and decrease the rate
      of association in tetramers. From these observations, we conclude that the
      tetramers constitute a heterogeneous population, the members of which are
      dissociated by pressure according to individual molecular properties that can be
      retained over periods of time much longer than the time for equilibration of the
      dissociation. The dissociation of dimers exhibits the characteristics of the
      classical stochastic chemical equilibria, while those of the tetramers, like the
      more complex protein aggregates, must already be considered similar to the
      deterministic mechanical equilibria of macroscopic bodies.

PMID- 1993177
TI  - Structure at 2.5-A resolution of chemically synthesized human immunodeficiency
      virus type 1 protease complexed with a hydroxyethylene-based inhibitor.
AB  - The crystal structure of a complex between chemically synthesized human
      immunodeficiency virus type 1 (HIV-1) protease and an octapeptide inhibitor has
      been refined to an R factor of 0.138 at 2.5-A resolution. The substrate-based
      inhibitor, H-Val-Ser-Gln-Asn-Leu psi [CH(OH)CH2]Val-Ile-Val-OH (U-85548e)
      contains a hydroxyethylene isostere replacement at the scissile bond that is
      believed to mimic the tetrahedral transition state of the proteolytic reaction.
      This potent inhibitor has Ki less than 1 nM and was developed as an active-site
      titrant of the HIV-1 protease. The inhibitor binds in an extended conformation
      and is involved in beta-sheet interactions with the active-site floor and flaps
      of the enzyme, which form the substrate/inhibitor cavity. The inhibitor
      diastereomer has the S configuration at the chiral carbon atom of the
      hydroxyethylene insert, and the hydroxyl group is within H-bonding distance of
      the two active-site carboxyl groups in the enzyme dimer. The two subunits of the
      enzyme are related by a pseudodyad, which superposes them at a 178 degrees
      rotation. The main difference between the subunits is in the beta turns of the
      flaps, which have different conformations in the two monomers. The inhibitor has
      a clear preferred orientation in the active site and the alternative
      conformation, if any, is a minor one (occupancy of less than 30%). A new model of
      the enzymatic mechanism is proposed in which the proteolytic reaction is viewed
      as a one-step process during which the nucleophile (water molecule) and
      electrophile (an acidic proton) attack the scissile bond in a concerted manner.

PMID- 1993178
TI  - Isolation and characterization of a cDNA from a human histone H2B gene which is
      reciprocally expressed in relation to replication-dependent H2B histone genes
      during HL60 cell differentiation.
AB  - A variant human histone H2B cDNA (HHC289) has been cloned and characterized and
      shown to have a complex pattern of regulation with respect to the HeLa S3 cell
      cycle and HL60 cell differentiation. The H2B protein coding region of HHC289 is
      flanked at the 3' end by a 1798-nt nontranslated trailer that contains a region
      of hyphenated dyad symmetry and a poly(A) addition sequence, followed by a
      poly(A) tail. Nuclear run-on transcription analysis revealed a 2-fold increase in
      transcription of the HHC289 gene during S phase, in comparison to replication
      dependent human histone genes which exhibit a 2-3-fold increase in transcription
      during S phase. Northern blot analysis indicated that the levels of the 2300-nt
      HHC289 mRNA species did not vary significantly during the HeLa S3 cell cycle, in
      comparison to replication-dependent H2B mRNAs which are elevated 15-fold during S
      phase. Northern blot analysis also revealed a reciprocal relationship during the
      onset of HL60 differentiation between the expression of the HHC289 H2B gene and
      the replication-dependent H2B genes. The levels of the 2300-nt HHC289 H2B species
      increased approximately 10-fold during HL60 cell differentiation whereas the
      levels of cell cycle dependent H2B mRNAs decreased to less than 1% of those in
      proliferating cells. These results suggest that complex transcriptional and
      posttranscriptional regulatory mechanisms control cellular levels of mRNAs from
      various human H2B histone genes during progression through the cell cycle and at
      the onset of differentiation.

PMID- 1993179
TI  - A comparison of the binding of methylated cap analogues to wheat germ protein
      synthesis initiation factors 4F and (iso)4F.
AB  - The binding of the 5'-terminal cap analogues m7GpppG and m7GTP to wheat germ
      protein synthesis initiation factors eIF-4F and eIF-(iso)4F as a function of pH,
      ionic strength, and temperature is described. Equilibrium binding data indicate
      that eIF-4F and eIF-(iso)4F have different mechanisms for interacting with the 5'
      cap structure, but the complexes formed between m7GpppG and wheat germ factor eIF
      (iso)4F more closely resemble complexes formed between this cap analogue and
      either mammalian eIF-4E or eIF-4F. The binding of these initiation factors to the
      hypermethylated cap analogues m2,7GMP, m2,7GpppG, and m2,2,7GpppG is also
      investigated. The differences in affinity of eIF-4F and eIF-(iso)4F for the
      hypermethylated 5'-terminal cap structures suggest that these factors may have
      discriminatory activity.

PMID- 1993180
TI  - Gene structure and chromosomal localization of plasma kallikrein.
AB  - Plasma kallikrein (Fletcher factor) is a hepatic serine proteinase that
      participated in the early phase of blood coagulation. From two genomic libraries,
      we succeeded to isolate four overlapping clones representing the entire rat
      plasma kallikrein gene. Using selective DNA sequencing, polymerase chain
      reactions, and restriction mapping, we demonstrated that the gene for rat plasma
      kallikrein was 22 kb in length. Similar to human factor XI [Asakai et al. (1987)
      Biochemistry 26, 7221-7228], we also found that the plasma kallikrein gene is
      composed of 15 exons and 14 introns. A potential transcription initiation step
      was determined by a novel application of the polymerase chain reaction technique.
      Computer analysis of the 5'-promoter region of this gene revealed some putative
      control elements that might regulate the rat plasma kallikrein gene expression.
      These data and the results of chromosomal localization reported in the present
      study for mouse (chromosome 8) and human (chromosome 4) plasma kallikrein genes
      strongly corroborate a genic duplication event from a common ancestor to both
      plasma kallikren and factor XI.

PMID- 1993181
TI  - Nucleotide sequence analysis of the Pseudomonas putida PpG7 salicylate
      hydroxylase gene (nahG) and its 3'-flanking region.
AB  - Gene nahG of naphthalene/salicylate catabolic plasmid NAH7 encodes a protein of
      molecular weight 45,000, salicylate hydroxylase. This enzyme catalyzes the
      formation of catechol from salicylate, a key intermediate in naphthalene
      catabolism. DNA sequence analysis of the 3.1-kilobase HindIII fragment containing
      the nahG locus reveals an open reading frame (ORF) of 1305 base pairs that
      corresponds to a protein of 434 amino acid residues. The predicted amino acid
      sequence of salicylate hydroxylase is in agreement with the molecular weight, NH2
      terminal amino acid sequence, and total amino acid composition of the purified
      salicylate hydroxylase [You, I.-S., Murray, R. I., Jollie, D., & Gunsalus, I. C.
      (1990) Biochem. Biophys. Res. Commun. 169, 1049-1054]. The amino acid sequence
      between positions 8 and 37 of salicylate hydroxylase shows homology with known
      ADP binding sites of other FAD-containing oxidoreductases, thus confirming its
      biochemical function. The sequence of the Pseudomonas putida salicylate
      hydroxylase was compared with those of other similar flavoproteins. A small DNA
      segment (831 base pairs) disrupts the continuity of the known gene order nahG and
      nahH, the latter encoding catechol 2,3-dioxygenase. The complete nucleotide
      sequence of the intergenic region spanning genes nahG and nahH has been
      determined and its biological role proposed.

PMID- 1993182
TI  - Comparative circular dichroism and fluorescence studies of
      oligodeoxyribonucleotide and oligodeoxyribonucleoside methylphosphonate
      pyrimidine strands in duplex and triplex formation.
AB  - An analogue of the homopyrimidine oligodeoxyribonucleotide d(CT)8 has been
      synthesized. This analogue, d(CT)8 contains nonionic methylphosphonate
      internucleoside linkages. The pH-dependent conformational transitions of d(CT)8
      have been studied and its ability to form duplexes and triplexes with the normal
      homopurine oligonucleotide d(AG)8 has also been investigated as a function of pH.
      Circular dichroism spectroscopy and ethidium bromide fluorescence enhancement
      have been used to monitor pH-dependent conformational transitions driven by the
      protonation of cytosine residues, and the different behavior of d(CT)8 and d(CT)8
      has been compared. It was possible to form self-associated complexes by using
      either d(CT)8 or d(CT)8, and both compounds combined with d(AG)8 to form duplex
      or triplex DNA. At neutral pH, the CD spectrum of d(AG)8.d(CT)8 duplex was quite
      different from the CD spectrum of d(AG)8.d(CT)8 duplex, reflecting most likely a
      difference in conformation. The duplex to triplex transition characteristic of
      this DNA sequence occurred at a lower pH when d(CT)8 was substituted for d(CT)8;
      however, at pH 4.2, triplex containing d(CT)8 was similar in conformation to
      triplex containing d(CT)8. Several of these observations can be related to the
      alterations in electrostatic and steric interactions that occur when the
      negatively charged phosphodiester backbone of d(CT)8 is replaced with a nonionic
      methylphosphonate backbone.

PMID- 1993183
TI  - Sequence-specific 1H NMR assignments and structural characterization of bovine
      seminal fluid protein PDC-109 domain b.
AB  - Sequence-specific resonance assignments for the isolated second or b domain of
      the bovine seminal fluid protein PDC-109 have been obtained from analysis of two
      dimensional 1H NMR experiments recorded at 500 MHz. These assignments include the
      identification of all aromatic and most aliphatic amino acid resonances.
      Stereospecific assignment of resonances stemming from the Val2 CH3 gamma,gamma'
      groups and from seven CH beta,beta' geminal pairs has been accomplished by
      analysis of 3J alpha beta coupling constants in conjunction with patterns of
      cross-peak intensities observed in two-dimensional nuclear Overhauser effect
      (NOESY) spectra. Analysis of NOESY and 3J alpha NH data reveals a small
      antiparallel beta-sheet involving stretches containing residues 25-28 and 39-42,
      a cis-proline residue (Pro4), antiparallel strands consisting of residues 1-3, 5
      7, and 10-13, and an aromatic cluster composed of Tyr7, Trp26, and Tyr33. The
      results of distance geometry and restrained molecular dynamics calculations
      indicate that the global fold of the PDC-109 b domain, a type II module related
      to those found in fibronectin, is somewhat different from that predicted by
      modeling the structure on the basis of homology between type II and kringle
      units. A shallow depression in the molecular surface which presents a solvent
      exposed hydrophobic area--a potential ligand-binding site-is identified in the
      NMR-based models.

PMID- 1993184
TI  - Existence of two D-alanine:D-alanine ligases in Escherichia coli: cloning and
      sequencing of the ddlA gene and purification and characterization of the DdlA and
      DdlB enzymes.
AB  - Two distinct genes encoding D-alanine:D-alanine (D-Ala-D-Ala) ligase (ADP
      forming) activity in Escherichia coli have been cloned by complementation of E.
      coli strain ST640(lambda 112) deficient in D-Ala-D-Ala ligase activity with a
      lambda library of E. coli DNA. One of the two genes, designated as ddlB, is
      identical with the ddl gene already sequenced [Robinson, A.C., Kenan, D.L.,
      Sweeney, J., & Donachie, W.D. (1986) J. Bacteriol. 167, 809-817]. We describe the
      subcloning and DNA sequencing of the other gene, designated as ddlA on the basis
      of similarities with the Salmonella typhimurium ddlA gene [Daub, E., Zawadzke,
      L.E., Botstein, D., & Walsh, C.T. (1988) Biochemistry 27, 3701-3708]. The
      predicted amino acid sequence of the E. coli DdlA enzyme shows 90% homology with
      the S. typhimurium DdlA sequence. The ddlB gene was subcloned by use of the
      polymerase chain reaction into an expression vector containing an optimized
      ribosome binding site, which expressed the DdlB enzyme to greater than 50%
      soluble cell protein. Both DdlA and DdlB enzymes were purified to greater than
      90% homogeneity and characterized kinetically.

PMID- 1993185
TI  - Transbilayer and interbilayer phospholipid exchange in
      dimyristoylphosphatidylcholine/dimyristoylphosphatidylethanolamine large
      unilamellar vesicles.
AB  - The rates of spontaneous interbilayer and transbilayer exchange of
      [3H]dimyristoylphosphatidylcholine ([3H]DMPC) were examined in DMPC and
      DMPC/dimyristoylphosphatidylethanolamine (DMPE) large unilamellar vesicles in the
      liquid-crystalline-, gel-, and mixed-phase states. DMPC desorption rates from
      either gel or liquid-crystalline phases containing DMPE are very similar to the
      corresponding rates from pure DMPC gel or liquid-crystalline phases. This is not
      the case for DMPC desorption from distearoylphosphatidylcholine (DSPC)-containing
      gel phases, where the desorption rates are significantly faster than from a pure
      DMPC gel phase [Wimley, W. C., & Thompson, T. E. (1990) Biochemistry 29, 1296
      1303]. We proposed that the DMPC/DSPC behavior results from packing defects in
      gel phases composed of both DMPC and DSPC molecules because of the four-carbon
      difference in the acyl chain lengths of the two species. The present results
      strongly support this hypothesis because no such anomalous behavior is observed
      in DMPC/DMPE, which is similar to DMPC/DSPC in phase behavior but does not have
      the chain length difference. The inclusion of 10-30 mol % DMPE in DMPC bilayers
      was also found to have a significant effect on the rate of transbilayer movement
      (flip-flop) of [3H]DMPC in the liquid-crystalline phase. Between 10 and 30 mol %
      DMPE, flip-flop of DMPC is slowed by at least 10-fold relative to flip-flop in
      DMPC bilayers, and the entropy and enthalpy of flip-flop activation are both
      substantially decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1993186
TI  - Degradation of dilauroylphosphatidylcholine by phospholipase A2 in monolayers
      containing glycosphingolipids.
AB  - The ability of phospholipase A2 from porcine pancreas to degrade all of the
      available dilauroylphosphatidylcholine in mixed monolayers with
      galactocerebroside, sulfatide, or ganglioside GM1 was investigated at different
      constant surface pressures. Under the conditions used the interfacial
      glycosphingolipid composition was continuously enriched as the enzyme action
      proceeded. The total percentage of phospholipid degradation depends on the
      surface pressure and on the type of glycosphingolipid. The presence of sulfatide
      activates the enzyme while galactocerebroside and ganglioside GM1 are inhibitory.
      The extent of phospholipid hydrolysis is independent of the effect of
      glycosphingolipids on the enzyme velocity. This is so when the latter is measured
      either in conditions of constant glycosphingolipid composition and zero-order
      kinetics [Bianco, I.D., Fidelio, G.D., & Maggio, B. (1989) Biochem. J. 258, 95
      99] or under variable surface composition as in the present work. The modulation
      of phospholipase A2 activity by glycosphingolipids operates at two independent
      levels. One controls the rate of enzyme activity, and the other modulates the
      total extent of substrate degradation. This depends on the initial interaction of
      the enzyme with the interface. The glycosphingolipid effect on the activity is
      different depending on whether the enzyme has access to the substrate from the
      subphase or is already adsorbed to the lipid interface.

PMID- 1993187
TI  - Resonance Raman characterization of Rhodobacter sphaeroides reaction centers
      bearing site-directed mutations at tyrosine M210.
AB  - Resonance Raman (RR) spectroscopy and low-temperature absorption spectroscopy
      have been used to investigate the structural changes in the reaction centers
      (RCs) of Rhodobacter sphaeroides induced by site-specific mutations on the
      tyrosine (Y) M210 residue. RCs in which Y M210 has been genetically replaced with
      phenylalanine (F) or leucine (L) exhibit a 5-fold decrease in their primary
      electron-transfer kinetics (Finkele et al., 1990). The general similarity of RR
      spectra of the wild-type RCs as compared to those of the two mutant RCs indicates
      that no significant global structural changes occur upon mutation at the level of
      any of the six bacteriochlorin pigments. In the RR spectra of the two mutant RCs
      there is a conspicuous absence of contributions from the BPheM prosthetic group,
      which is interpreted in terms of a change in the resonance enhancement conditions
      of this chromophore. Low-temperature adsorption spectroscopy reveals marked
      shifts in the Qx absorption band of BPheM. This shift is interpreted as arising
      from a destabilization of the protein in the vicinity of BPheM and accounts for
      the change in resonance condition for this chromophore in its RR contributions.
      As well, there is a 3-nm red shift of the Qy absorption band of the BChls from
      803 to 806 nm for the mutant RCs. Difference RR spectra yielding structural
      information concerning, selectively, the primary donor (P) indicate that the
      structure of the P binding pocket is conserved for these mutant RCs. The tyrosine
      M210 is not observed to be engaged in a hydrogen bond with either of the acetyl
      or keto carbonyls of P.

PMID- 1993188
TI  - Molecular insights into enzymes of membrane bilayer assembly.

PMID- 1993189
TI  - Transbilayer transport of phosphatidic acid in response to transmembrane pH
      gradients.
AB  - Preliminary studies have shown that asymmetric transbilayer distributions of
      phosphatidic acid (PA) can be induced by transmembrane pH gradients (delta pH) in
      large unilamellar vesicles [Hope et al. (1989) Biochemistry 28, 4181-4187]. Here
      the mechanism of PA transport is examined employing TNS as a fluorescent probe of
      lipid asymmetry. It is shown that the kinetics of PA transport are consistent
      with the transport of the uncharged (protonated) form. Transport of the neutral
      form can be rapid, exhibiting half-times for transbilayer transport of
      approximately 25 s at 45 degrees C. It is also shown that PA transport is
      associated with a large activation energy (28 kcal/mol) similar to that observed
      for phosphatidylglycerol. The maximum induced transbilayer asymmetry of PA
      corresponded to approximately 95% on the inner monolayer for vesicles containing
      5 mol % PA.

PMID- 1993190
TI  - Phosphatidyl-Tris rather than N-acylphosphatidylserine is synthesized by
      Rhodopseudomonas sphaeroides grown in Tris-containing media.
AB  - We have synthesized 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho(N-oleoyl)serine (N
      acyl-PS) and 1,2-dioleoyl-sn-glycero-3-phospho-Tris (phosphatidyl-Tris) and have
      characterized both phospholipids by their chemical and chromatographic
      properties, as well as by their IR, 13C NMR, and 1H NMR spectra. Comparison of
      these data with those reported for a phospholipid isolated from Rhodopseudomonas
      sphaeroides grown in Tris-supplemented media [Donohue et al. (1982) Biochemistry
      21, 2765-2773] indicates that R. sphaeroides synthesizes phosphatidyl-Tris rather
      than N-acyl-PS.

PMID- 1993191
TI  - Effects of detergent environments on the photocycle of purified monomeric
      bacteriorhodopsin.
AB  - Time-resolved difference spectra have been obtained for the photocycle of
      delipidated bacteriorhodopsin monomers (d-BR) in six different detergent micelle
      environments that were prepared by two new detergent-exchange techniques. A
      global kinetic analysis of the photocycle spectra for d-BR in each detergent
      environment was performed. Comparison of these results with those obtained for
      the photocycle of bacteriorhodopsin in purple membrane (PM) shows that there is
      one fewer kinetically distinguishable process for monomeric BR between the decay
      of the K intermediate and the rise of the M intermediate. Assuming a sequential
      pathway occurs in the photocycle, it appears that the equilibrium between the L
      and M intermediates is reached much more rapidly in the detergent micelles. This
      is attributed to a more direct interaction between Asp-85 and the proton on the
      nitrogen of the Schiff base of retinal for BR in the detergents. Equilibrium
      concentrations of late photocycle intermediates are also altered in detergents.
      The later steps of the photocycle, including the decay of the M intermediate, are
      slowed in detergents with rings in their hydrocarbon region. This is attributed
      to effects on conformational changes occurring during the decay of M and/or other
      later photocycle intermediates. The lifetime of dark adaptation of light-adapted
      d-BR in different detergent environments increases in environments where the
      lifetime of the M intermediate increases. These results suggest that the high
      percentage of either unsaturated or methyl-branched lipids in PM and the
      membranes of other retinal proteins may be important for their effective
      functioning.

PMID- 1993192
TI  - Phosphoenolpyruvate-dependent mannitol phosphotransferase system of Escherichia
      coli: overexpression, purification, and characterization of the enzymatically
      active C-terminal domain of enzyme IImtl equivalent to enzyme IIImtl.
AB  - The extreme C-terminus (Ser-490 to Lys-637) of the Escherichia coli EIImtl was
      subcloned to test structural and mechanistic proposals about the existence of an
      EIII-like domain in this enzyme. Oligonucleotide-directed mutagenesis was used to
      produce a unique NcoI restriction site and, at the same time, to change Ser-490
      into methionine in a flexible region in front of the proposed EIII-like domain.
      The 16-kDa C-terminal domain (CI) was overexpressed in Escherichia coli,
      purified, and analyzed in vitro for catalytic activity in the presence of an
      EIImtl mutated at its first phosphorylation site, His-554 (EII-H554A). The
      results presented show that this domain can be expressed as a structurally
      stable, enzymatically active entity which is able to restore the PEP-dependent
      phosphorylation activity of the mutant EIImtl-H554A to 25% of wild-type levels.
      To demonstrate the EIII activity of the CI domain in a more direct way, we also
      substituted it for EIIImtl in the Staphylococcus carnosus system. The CI domain
      was active in transferring the phosphoryl group to Staph. carnosus EII; however,
      it was 6.5 times less active compared to Staph. carnosus EIIImtl itself. EIIImtl
      from Staph. carnosus, on the other hand, was able to substitute for the isolated
      C-terminal domain in the E. coli mannitol phosphorylation assay; however, it
      appeared to be 2 or 3 times less effective.

PMID- 1993193
TI  - Sites of contact of mRNA with 16S rRNA and 23S rRNA in the Escherichia coli
      ribosome.
AB  - The locations of close encounter between ribosomal RNA (rRNA) and messenger RNA
      (mRNA) were determined by photochemical cross-linking experiments that employ an
      artificial mRNA, 51 nucleotides long, containing 14 U residues that were randomly
      substituted by 1-4 4-thiouridine (s4U) residues. The mRNA was bound to 70S
      ribosomes or 30S subunits and then was irradiated at 366 nm to activate cross
      linking between the s4U residues and rRNA. Cross-linking occurred to both 16S
      rRNA and 23S RNA. The rRNA was then analyzed by a series of reverse transcriptase
      experiments to determine the locations of cross-linking. Twelve sites in the 16S
      rRNA and two sites in the 23S rRNA have been detected. In the 16S rRNA, two of
      the sites (U1381, C1395) are in the middle part of the secondary structure close
      to position C1400, and the remaining sites (G413, U421, G424; A532; G693; U723;
      A845; G1131/C1132; G1300; G1338) are distributed between six regions that are
      peripheral in the secondary structure. In the 23S rRNA, one site (U1065) is
      located in the GTPase center close to A1067, the site of thiostrepton-resistance
      methylation in domain II, and the other site (U887) is located a short distance
      away also in domain II. The distribution of these rRNA sites in the ribosome
      specifies an mRNA track that is consistent with other information. In addition,
      some of the contact points represent new constraints for the three-dimensional
      folding of the rRNA.

PMID- 1993194
TI  - Properties of a U1/mRNA 5' splice site duplex containing pseudouridine as
      measured by thermodynamic and NMR methods.
AB  - Three RNA undecamers, 5'AUAC psi psi ACCUG (psi = pseudouridine), 5'AUACUUACCUG,
      and their complementary 11-mer 5'CAGGUAAGUAU, have been chemically synthesized by
      phosphite triester chemistry on a controlled-pore glass (CPG) support. The two
      duplexes formed with these molecules, 5'AUAC psi psi ACCUG/5'CAGGUAAGUAU and
      5'AUACUUACCUG/5'CAGGUAAGUAU, represent the 5' end of human U1 snRNA paired to the
      mRNA consensus 5' splice site. In one undecamer, pseudouridines are incorporated
      at those positions corresponding to the native in vivo U1 snRNA, while the other
      (control) undecamer contains only uridine. Surprisingly, the NMR data show that
      the extra imino proton of the pseudouridines, which is found in the major groove
      and is presumably not hydrogen bonded, is clearly visible in the imino proton NMR
      spectrum at pH 6. This result suggests that the structure of the RNA restricts
      access of solvent to the major groove, slowing the exchange of the pseudouridine
      NH1 imino proton. A comparison of the thermodynamic properties of the two
      duplexes show that the free energy of duplex formation is unchanged by the
      substitution of pseudouridine for uridine.

PMID- 1993195
TI  - Kinetic and equilibrium analysis of a threading intercalation mode: DNA sequence
      and ion effects.
AB  - The interaction of a symmetric naphthalene diimide with alkylamino substituents
      at each imide position was investigated with the alternating sequence polymers,
      poly[d(A-T)]2 and poly[d(G-C)]2. Spectrophotometric binding studies indicate
      strong binding of the diimide to both sequences although the GC binding constant
      is 20-25 times larger than the AT binding constant. Analysis of the effects of
      salt concentration on the binding equilibria shows that the diimide forms two ion
      pairs in its complex with both polymers as expected for a simple dication.
      Stopped-flow kinetics experiments demonstrate that the diimide both associates
      and dissociates from DNA more slowly than classical intercalators with similar
      binding constants. Analysis of salt concentration effects on dissociation
      kinetics rate constants (kd) reveals that slopes in log kd versus log [Na+] plots
      are only approximately half the value obtained for classical dicationic
      intercalators that have both charged groups in the same groove. These kinetics
      results support a threading intercalation model, with one charged diimide
      substituent in each of the DNA grooves rather than with both side chains in the
      same groove, for the diimide complex with DNA. In the rate-determining step of
      the mechanism for dissociation of a threading complex only one ion pair is
      broken; the free side chain can then slide between base pairs to put both diimide
      side chains in the same groove, and this is followed by rapid full dissociation
      of the diimide. This sequential release of ion pairs makes the dissociation slope
      for dicationic threading intercalators more similar to the slope for classical
      monocationic intercalating ligands.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1993196
TI  - NMR studies of the exocyclic 1,N6-ethenodeoxyadenosine adduct (epsilon dA)
      opposite thymidine in a DNA duplex. Nonplanar alignment of epsilon dA(anti) and
      dT(anti) at the lesion site.
AB  - Two-dimensional proton NMR studies are reported on the complementary d(C-A-T-G-T
      G-T-A-C).d(G-T-A-C-epsilon A-C-A-T-G) nonanucleotide duplex (designated epsilon
      dA.dT 9-mer duplex) containing 1,N6-ethenodeoxyadenosine (epsilon dA), a
      carcinogen-DNA adduct, positioned opposite thymidine in the center of the helix.
      Our NMR studies have focused on the conformation of the epsilon dA.dT 9-mer
      duplex at neutral pH with emphasis on defining the alignment at the dT5.epsilon
      dA14 lesion site. The through-space NOE distance connectivities establish that
      both dT5 and epsilon dA14 adopt anti glycosidic torsion angles, are directed into
      the interior of the helix, and stack with flanking Watson-Crick dG4.dC15 and
      dG6.dC13 pairs. Furthermore, the d(G4-T5-G6).d(C13-epsilon A14-C15) trinucleotide
      segment centered about the dT5.epsilon dA14 lesion site adopts a right-handed
      helical conformation in solution. Energy minimization computations were
      undertaken starting from six different alignments of dT5(anti) and epsilon
      dA14(anti) at the lesion site and were guided by distance constraints defined by
      lower and upper bounds estimated from NOESY data sets on the epsilon dA.dT 9-mer
      duplex. Two families of energy-minimized structures were identified with the dT5
      displaced toward either the flanking dG4.dC15 or the dG6.dC13 base pair. These
      structures can be differentiated on the basis of the observed NOEs from the imino
      proton of dT5 to the imino proton of dG4 but not dG6 and to the amino protons of
      dC15 but not dC13 that were not included in the constraints data set used in
      energy minimization. Our NMR data are consistent with a nonplanar alignment of
      epsilon dA14(anti) and dT5(anti) with dT5 displaced toward the flanking dG4.dC15
      base pair within the d(G4-T5-G6).d(C13-epsilon A14-C15) segment of the epsilon
      dA.dT 9-mer duplex.

PMID- 1993197
TI  - NMR studies of the exocyclic 1,N6-ethenodeoxyadenosine adduct (epsilon dA)
      opposite deoxyguanosine in a DNA duplex. Epsilon dA(syn).dG(anti) pairing at the
      lesion site.
AB  - Proton NMR studies are reported on the complementary d(C-A-T-G-G-G-T-A-C).d(G-T-A
      C-epsilon A-C-A-T-G) nonanucleotide duplex (designated epsilon dA.dG 9-mer
      duplex), which contains exocyclic adduct 1,N6-ethenodeoxyadenosine positioned
      opposite deoxyguanosine in the center of the helix. The present study focuses on
      the alignment of dG5 and epsilon dA14 at the lesion site in the epsilon dA.dG 9
      mer duplex at neutral pH. This alignment has been characterized by monitoring the
      NOEs originating from the NH1 proton of dG5 and the H2, H5, and H7/H8 protons of
      epsilon dA14 in the central d(G4-G5-G6).d(C13-epsilon A14-C15) trinucleotide
      segment of the epsilon dA.dG 9-mer duplex. These NOE patterns establish that
      epsilon dA14 adopts a syn glycosidic torsion angle that positions the exocyclic
      ring toward the major groove edge while all the other bases including dG5 adopt
      anti glycosidic torsion angles. We detect a set of intra- and interstrand NOEs
      between protons (exchangeable and nonexchangeable) on adjacent residues in the
      d(G4-G5-G6).d(C13-epsilon A14-C15) trinucleotide segment which establish
      formation of right-handed helical conformations on both strands and stacking of
      the dG5(anti).epsilon dA14(syn) pair between stable dG4.dC15 and dG6.dC13 pairs.
      The energy-minimized conformation of the central d(G4-G5-G6).d(C13-epsilon A14
      C15) segment establishes that the dG5(anti).epsilon dA14(syn) alignment is
      stabilized by two hydrogen bonds from the NH1 and NH2-2 of dG5(anti) to N9 and N1
      of epsilon dA14(syn), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1993198
TI  - Two-dimensional 1H nuclear magnetic resonance study of AaH IT, an anti-insect
      toxin from the scorpion Androctonus australis Hector. Sequential resonance
      assignments and folding of the polypeptide chain.
AB  - Sequence-specific nuclear magnetic resonance assignments for the polypeptide
      backbone and for most of the amino acid side-chain protons, as well as the
      general folding of AaH IT, are described. AaH IT is a neurotoxin purified from
      the venom of the scorpion Androctonus australis Hector and is specifically active
      on the insect nervous system. The secondary structure and the hydrogen-bonding
      patterns in the regular secondary structure elements are deduced from nuclear
      Overhauser effects and the sequence locations of the slowly exchanging amide
      protons. The backbone folding is determined by distance geometry calculations
      with the DISMAN program. The regular secondary structure includes two and a half
      turns of alpha-helix running from residues 21 to 30 and a three-stranded
      antiparallel beta-sheet including peptides 3-5, 34-38, and 41-46. Two tight turns
      are present, one connecting the end of the alpha-helix to an external strand of
      the beta-sheet, i.e., turn 31-34, and another connecting this same strand to the
      central one, i.e., turn 38-41. These structure elements are very similar to the
      secondary structure reported in single crystals for either variant 3 from the
      scorpion Centruroides sculpturatus Ewing (CsE V3) or toxin II from the scorpion
      A. australis Hector (AaH II). The differences in the specificity of these related
      proteins, which are able to discriminate between mammalian and insect voltage
      dependent sodium channels of excitable tissues, are most probably brought about
      by the position of the C-terminal peptide with regard to a hydrophobic surface
      common to all scorpion toxins examined thus far. This surface is made of an
      aromatic cluster that is surrounded by long hydrophobic side-chain residues, as
      well as the loops protruding out of it. Thus, the interaction of a given scorpion
      toxin with its receptor might well be governed by the presence of this solvent
      exposed hydrophobic surface, whereas adjacent areas modulate the specificity of
      the interaction.

PMID- 1993200
TI  - 6-(Difluoromethyl)tryptophan as a probe for substrate activation during the
      catalysis of tryptophanase.
AB  - A substrate analogue, 6-(difluoromethyl)tryptophan, was developed and
      characterized for mechanistic investigation of tryptophanase. The utility of this
      derivative was based on its ability to partition between fluoride elimination and
      carbon-carbon bond scission during tryptophan metabolism. The non-enzymatic
      hydrolysis to 6-formyltryptophan occurred slowly under neutral conditions with a
      first-order rate constant of 0.0039 min-1. This process, however, was accelerated
      by 10(4)-fold upon deprotonation of the indolyl nitrogen (N-1) at high pH.
      Tryptophanase did not detectably facilitate this hydrolysis reaction, since no
      protein-dependent conversion of the difluoromethyl group was detected. Instead,
      the enzyme accepted the fluorinated species as an analogue of tryptophan and
      catalyzed the corresponding formation of 6-(difluoromethyl)indole, pyruvate, and
      ammonium ion. Anionic intermediates are therefore not expected to form during the
      catalytic activation of the indolyl moiety. Instead, aromatic protonation likely
      promotes the release of indole during enzymatic degradation of tryptophan.

PMID- 1993199
TI  - Structural microheterogeneity of a tryptophan residue required for efficient
      biological electron transfer between putidaredoxin and cytochrome P-450cam.
AB  - The carboxy-terminal tryptophan of putidaredoxin, the Fe2S2.Cys4 iron-sulfur
      physiological redox partner of cytochrome P-450cam, is essential for maximal
      biological activity [Davies, M. D., Qin, L., Beck, J. L., Suslick, K. S., Koga,
      H., Horiuchi, T., & Sligar, S. G. (1990) J. Am. Chem. Soc. 112, 7396-7398]. This
      single tryptophan-containing protein thus represents an excellent system for
      studying the solution dynamics of a residue directly implicated in an electron
      transfer pathway. Steady-state and time-resolved measurements of the tryptophan
      fluorescence have been conducted across the emission spectrum as a function of
      redox state to probe potential structural changes which might be candidates for
      structural gating phenomena. The steady-state emission spectrum (lambda max = 358
      nm) and anisotropy (alpha = 0.04) suggest that Trp-106 is very solvent-exposed
      and rotating partially free of global protein constraints. The time-resolved
      fluorescence kinetics for both oxidized and reduced putidaredoxin are fit best
      with three discrete components of approximately 5, 2, and 0.3 ns. The lifetime
      components were assigned to physical species with iodide ion quenching
      experiments, where differential quenching of the longer components was observed
      (k tau = 2 = 5.9 X 10(8) M-1 s-1, k tau = 5 = 1.3 X 10(8) M-1 s-1). These
      findings suggest that the multiexponential fluorescence decay results from ground
      state conformational microheterogeneity and thus demonstrate that the essential
      tryptophan exists in at least two distinguishable conformations. Small
      differences in the relative proportions of the components between redox states
      were observed but not cleanly resolved.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1993201
TI  - Roles of the beta 146 histidyl residue in the molecular basis of the Bohr effect
      of hemoglobin: a proton nuclear magnetic resonance study.
AB  - Assessment of the roles of the carboxyl-terminal beta 146 histidyl residues in
      the alkaline Bohr effect in human normal adult hemoglobin by high-resolution
      proton nuclear magnetic resonance spectroscopy requires assignment of the
      resonances corresponding to these residues. Previous resonance assignments in low
      ionic strength buffers for the beta 146 histidyl residue in the carbonmonoxy form
      of hemoglobin have been controversial [see Ho and Russu (1987) Biochemistry 26,
      6299-6305; and references therein]. By a careful spectroscopic study of human
      normal adult hemoglobin, enzymatically prepared des(His146 beta)-hemoglobin, and
      the mutant hemoglobins Cowtown (beta 146His----Leu) and York (beta 146His---
      Pro), we have resolved some of these conflicting results. By a close incremental
      variation of pH over a wide range in chloride-free 0.1 M N-(2
      hydroxyethyl)piperazine-N'-2-ethanesulfonic acid buffer, a single resonance has
      been found to be consistently missing in the proton nuclear magnetic resonance
      spectra of these hemoglobin variants. The spectra of each of these variants show
      additional perturbations; therefore, the assignment has been confirmed by an
      incremental titration of buffer conditions to benchmark conditions, i.e., 0.2 M
      phosphate, where the assignment of this resonance is unambiguous. The strategy of
      incremental titration of buffer conditions also allows extension of this
      resonance assignment to spectra taken in 0.1 M [bis(2
      hydroxyethyl)amino]tris(hydroxymethyl)methane buffer. Participation of the beta
      146 histidyl residues in the Bohr effect has been calculated from the pK values
      determined for the assigned resonances in chloride-free 0.1 M N-(2
      hydroxyethyl)piperazine-N'-2-ethanesulfonic acid buffer. Our results indicate
      that the contribution of the beta 146 histidyl residues is 0.52 H+/hemoglobin
      tetramer at pH 7.6, markedly less than the 0.8 H+/hemoglobin tetramer estimated
      by study of the mutant hemoglobin Cowtown (beta 146His----Leu) by Shih and Perutz
      [(1987) J. Mol. Biol. 195, 419-422]. We have found that at least two histidyl
      residues in the carbonmonoxy form of this mutant have pK values that are
      perturbed, and we suggest that these pK differences may in part account for this
      discrepancy. Furthermore, summation of the positive contribution of the beta 146
      histidyl residues and the negative contribution of the beta 2 histidyl residues
      to the maximum Bohr effect measured in 0.1 M N-(2-hydroxyethyl)piperazine-N'-2
      ethanesulfonic acid buffer suggests that additional sites in the hemoglobin
      molecule account for proton release upon ligation greater than the contribution
      of the beta 146 histidyl residues.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1993202
TI  - 1H NMR study of the role of heme carboxylate side chains in modulating heme
      pocket structure and the mechanism of reconstitution of cytochrome b5.
AB  - 1H nuclear magnetic resonance spectroscopy was used to assign the hyperfine
      shifted resonances and determine the position of a side chain in the heme cavity
      of wild-type rat apocytochrome b5 reconstituted with a series of synthetic hemins
      possessing systematically perturbed carboxylate side chains. The hemins included
      protohemin derivatives with individually removed or pairwise shortened and
      lengthened carboxylate side chains, as well as (propionate)n(methyl)8-nporphine
      iron(III) isomers with n = 1-3 designed to force occupation of nonnative
      propionate sites. The resonance assignments were effected on the basis of
      available empirical heme contact shift correlations and steady-state nuclear
      Overhauser effect measurements in the low-spin oxidized proteins. The failure to
      detect holoproteins with certain hemins dictates that the stable holoproteins,
      unlike the case of myoglobin, demand the axial iron-His bonds and cannot
      accommodate carboxylate side chains at interior positions in the binding pocket.
      Hence, the heme pocket interior in cytochrome b5 is judged much less polar and
      less sterically accommodating than that of myoglobin. The propionate occupational
      preference was greatest as the native 7-propionate site, but also possible at the
      nonnative crystallographic 5-methyl or 8-methyl positions. Only for a propionate
      at the crystallographic 8-methyl position was a significant perturbation of the
      native molecular/electronic structure observed, and this was attributed to an
      alternative propionate-protein hydrogen bond at the crystallographic 8-methyl
      position. The structures of the transient protein complexes detected only shortly
      after reconstitution reveal that the initial encounter complexes during assembly
      of holoprotein from apoprotein and hemin involve one of the two alternate
      propionate-protein links at either the 7-propionate or native 8-methyl position.
      In a monopropionate hemin, this leads to the characterization of a new type of
      heme orientational disorder involving rotation about a N-Fe-N axis.

PMID- 1993203
TI  - A differential scanning calorimetric study of the thermal unfolding of seven
      mutant forms of phage T4 lysozyme.
AB  - High-sensitivity differential scanning calorimetry has been applied to the study
      of the reversible thermal unfolding of the lysozyme of T4 bacteriophage in which
      the threonine residue at position 157 has been replaced by seven different
      residues. High-resolution structures derived from X-ray crystallography have been
      reported for these and six other mutants by Alber et al. [Alber, T., Dao-Pin, S.,
      Wilson, K., Wozniak, J. A., Cook, S. P., & Matthews, B. W. (1987) Nature 330, 41
      46]. At pH 2.5 the changes relative to the wild-type protein in the standard free
      energy of unfolding produced by these mutations indicate apparent
      destabilizations of 0.6 kcal mol-1 (T157R) to 1.9 kcal mol-1 (T157I), whereas the
      changes in enthalpy of unfolding range from -5.8 kcal mol-1 (T157N) to 11.9 kcal
      mol-1 (T157E). Since the denaturations are in all cases accompanied by large
      changes in heat capacity amounting to 2.5 kcal K-1 mol-1, both the free energies
      and enthalpies are functions of temperature. An intriguing feature of the present
      results is the relatively large enthalpy changes and the corresponding
      compensating entropy changes. Our present understanding of the intramolecular
      energetics of proteins is insufficient to account for these changes.

PMID- 1993204
TI  - Inhibition by cyclopropylamine of the quinoprotein methylamine dehydrogenase is
      mechanism-based and causes covalent cross-linking of alpha and beta subunits.
AB  - Cyclopropylamine acted as a mechanism-based inhibitor of the quinoprotein
      methylamine dehydrogenase from Paracoccus denitrificans. The protein-bound
      quinone cofactor of this enzyme was rapidly reduced by addition of a
      stoichiometric amount of cyclopropylamine, but this compound did not serve as a
      substrate for the enzyme in the steady-state kinetic assay. Time-dependent
      inactivation of the enzyme by cyclopropylamine was observed only in the presence
      of a reoxidant. Saturation behavior was observed, and values of KI of 3.9 microM
      and K(inact) of 1.7 min-1 were determined. Enzyme inactivation was irreversible,
      as no restoration of activity was evident after gel filtration of methylamine
      dehydrogenase which had been incubated with cyclopropylamine in the presence of a
      reoxidant. The inactivated enzyme exhibited an altered absorption spectrum.
      Electrophoretic analysis of inactivated methylamine dehydrogenase indicated that
      covalent cross-linking of the alpha and beta subunits of this alpha 2 beta 2
      oligomeric enzyme had occurred and that the quinone cofactor had been modified. A
      mechanism for this inhibition is proposed which is based upon the data presented
      and is consistent with the available structural information on methylamine
      dehydrogenase.

PMID- 1993205
TI  - Construction, expression, and purification of recombinant kringle 1 of human
      plasminogen and analysis of its interaction with omega-amino acids.
AB  - An Escherichia coli expression vector, containing the alkaline phosphatase
      promoter and the stII heat-stable enterotoxin signal sequence, along with the
      cDNA of the kringle 1 (K1) region of human plasminogen (HPg), has been employed
      to express into the periplasmic space amino acid residues 82-163 (E163----D) of
      HPg. This region of the molecule contains the entire K1 domain (residues C84
      C162) of HPg, as well as two non-kringle amino-terminal amino acids (S82-E83)
      that are present in their normal locations in HPg and a carboxyl-terminal amino
      acid, D163, that results from mutation of the E163, normally present at this
      location in the HPg amino acid sequence. After purification of r-K1 by
      chromatographic techniques, we have investigated its omega-amino acid binding
      properties by titration calorimetry, intrinsic fluorescence, and differential
      scanning microcalorimetry (DSC). The antifibrinolytic agent, epsilon-aminocaproic
      acid (EACA), possesses a single binding site for r-K1. The thermodynamic
      properties of this interaction, studied by calorimetric titrations of the heats
      of binding with this ligand, reveal a Kd of 12 +/- 2 microM at 25 degrees C and
      pH 7.4, a corresponding delta G of -6.7 +/- 0.1 kcal/mol, a delta H of -3.6 +/-
      0.1 kcal/mol, and a delta S of 10.5 +/- 0.8 eu. The intrinsic fluorescence of r
      K1 decreases by approximately 44% when its binding site is saturated with EACA,
      and titrations of this perturbation with EACA lead to calculation of a Kd of
      approximately 13 microM, a value in good agreement with that obtained from
      titration calorimetric analysis. EACA represents the strongest binding ligand of
      a variety of simple aliphatic omega-amino acids examined. A cyclic analogue of
      EACA, trans-4-(aminomethyl)cyclohexanecarboxylic acid, interacts with r-K1 with
      an approximate 12-fold tighter Kd (1.0 +/- 0.2 microM). Investigations by DSC, at
      pH 7.4, demonstrate that a significant stabilization of the r-K1 structure occurs
      when EACA binds to this domain. The temperature of maximum heat capacity change
      (Tm) in the thermal denaturation of r-K1 increases from approximately 340.8 to
      359.1 K as a consequence of EACA binding. These studies demonstrate that a fully
      functional EACA-binding kringle from HPg can be expressed and secreted in E.
      coli, purified by techniques that do not require refolding, and investigated as
      an independent structural unit.

PMID- 1993206
TI  - Isolation and chemical characterization of two structurally and functionally
      distinct forms of botrocetin, the platelet coagglutinin isolated from the venom
      of Bothrops jararaca.
AB  - Two distinct forms of botrocetin, the von Willebrand factor (vWF)-dependent
      platelet coagglutinin isolated from the venom of the snake Bothrops jararaca,
      were purified and characterized structurally and functionally. The apparent
      molecular mass of the one-chain botrocetin was 28 kDa before and 32 kDa after
      reduction of disulfide bonds, while that of the two-chain botrocetin was 27 kDa
      before and 15/14.5 kDa after reduction. Amino acid composition of the two species
      revealed a similar high content of potentially acidic residues (greater than 60
      Asx and Glx residues/molecule) but significant differences in the content of Cys
      and Phe residues. The NH2-terminal sequence of the one-chain botrocetin was Ile
      Ile/Val-Ser-Pro-Pro-Val-Cys-Gly-Asn-Glu-. Two constituent polypeptides of the two
      chain botrocetin showed similar but different NH2-terminal sequences, distinct
      from that of the one-chain species: (alpha) Asp-Cys-Pro-Ser-Gly-Trp-Ser-Ser-Tyr
      Glu- and (beta) Asp-Cys-Pro-Pro-Asp-Trp-Ser-Ser-Tyr-Glu-. The carbohydrate
      content of both species was less than 2% of the total mass, and the pI was 4.0
      4.1 for the one-chain species, and 4.6, 5.3-5.4, and 7.7-7.8 for the two-chain
      species. No free sulfhydryl group was detected in each species. Both types of
      botrocetin were resistant to proteolysis at neutral pH. Incubation of 125I
      labeled one-chain botrocetin with the crude venom solution resulted in no
      detectable structural change. On a weight basis, the two-chain botrocetin was 34
      times more active than the one-chain form in promoting vWF binding to
      platelets.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1993207
TI  - Xenopus liver ferritin H subunit: cDNA sequence and mRNA production in the liver
      following estrogen treatment.
AB  - In vitro translation of liver mRNA from estrogen-treated Xenopus frogs yields two
      abundant polypeptides in the range of 20 kDa. DNA clones for one of these
      translation products were isolated and shown to be complementary to mRNA for the
      heavy subunit of ferritin. The predicted Xenopus amino acid sequence shares about
      86% identity with the ferritin heavy chain from bullfrogs and about 70% identity
      with the comparable mammalian and avian proteins. Clone identity was confirmed by
      hybridization selection followed by in vitro translation into translation
      products of 19.5-20 kDa. The nearly full-length cDNA clone, termed XlferH1,
      comprises 868 nucleotides plus 22 adenosines of the poly(A) tail, including 134
      nucleotides of the 5'-untranslated region, a 528-base coding region for 176 amino
      acids, and a 206-nucleotide 3'-untranslated region. The clone lacks 22
      nucleotides from the 5' end of the mRNA. The level of ferritin mRNA in the liver
      of estrogen-treated frogs was determined over time. The amount of this mRNA
      relative to total RNA decreased about 3-fold 14 days after estradiol-17 beta was
      administered. However, the hormone also elevated total RNA in the liver about 24
      fold. Hence, the total ferritin mRNA content of the liver increased to about 8
      times its initial amount. This pattern of gene expression was very similar to
      that for serum retinol binding protein. The estrogen induction of these two mRNAs
      appeared to parallel the overall stimulation of hepatic RNA synthesis.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1993208
TI  - Activity and structure of the active-site mutants R386Y and R386F of Escherichia
      coli aspartate aminotransferase.
AB  - Arginine-386, the active-site residue of Escherichia coli aspartate
      aminotransferase (EC 2.6.1.1) that binds the substrate alpha-carboxylate, was
      replaced with tyrosine and phenylalanine by site-directed mutagenesis. This
      experiment was undertaken to elucidate the roles of particular enzyme-substrate
      interactions in triggering the substrate-induced conformational change in the
      enzyme. The activity and crystal structure of the resulting mutants were
      examined. The apparent second-order rate constants of both of these mutants are
      reduced by more than 5 orders of magnitude as compared to that of wild-type
      enzyme, though R386Y is slightly more active than R386F. The 2.5-A resolution
      structure of R386F in its native state was determined by using difference Fourier
      methods. The overall structure is very similar to that of the wild-type enzyme in
      the open conformation. The position of the Phe-386 side chain, however, appears
      to shift with respect to that of Arg-386 in the wild-type enzyme and to form new
      contacts with neighboring residues.

PMID- 1993210
TI  - Program issue. The International Society for Heart Transplantation eleventh
      annual meeting and scientific sessions. April 7-9, 1991, Paris, France.

PMID- 1993209
TI  - Structural features of 5,10-dideaza-5,6,7,8-tetrahydrofolate that determine
      inhibition of mammalian glycinamide ribonucleotide formyltransferase.
AB  - We have investigated the structural features of 5,10-dideaza-5,6,7,8
      tetrahydrofolate (DDATHF) that determine the activity of this compound as an
      inhibitor of glycinamide ribonucleotide formyltransferase (GARFT) purified from
      mouse L1210 cells. 5-Deazatetrahydrofolate was as good an inhibitor of GARFT as
      DDATHF, indicating that isosteric replacement of nitrogen by carbon at the 5
      position of tetrahydrofolate is sufficient for inhibition of GARFT. 5,10
      Dideazafolic acid, 5,8,10-trideazatetrahydrofolate, and 2-desamino-5,10
      dideazatetrahydrofolate were poor inhibitors of GARFT, indicating that a reduced
      pyridopyrimidine ring, N-8, and the 2-amino group of DDATHF, respectively, play
      an important role in the binding of tetrahydrofolate analogues to this enzyme.
      DDATHF analogues in which the phenyl ring was replaced either by a cyclohexyl
      ring or by methylene groups retained activity as inhibitors. 5,10
      Dideazatetrahydrohomofolate was about 6 times more potent as an inhibitor of
      GARFT than DDATHF, but 5,10-dideazatetrahydronorfolate had about one-fifth of the
      activity of DDATHF. An analogue of DDATHF in which the glutamic acid side chain
      was replaced by aspartic acid (which was not a substrate for polyglutamation and
      was only weakly cytotoxic) was equiactive with DDATHF as an inhibitor of purified
      GARFT. Surprisingly, 5,10-dideazatetrahydropteroic acid was about as active as
      DDATHF as an inhibitor of GARFT, an indication that the glutamic acid in the side
      chain of DDATHF does not play a role in this ligand-enzyme interaction. The
      polyglutamate derivatives of DDATHF bound up to 100 times tighter to GARFT than
      DDATHF itself; longer chain polyglutamates conformed to Goldstein's zone B
      behavior under experimental conditions and were projected to be in zone C, i.e.,
      stoichiometric inhibition, in vivo. We conclude that the presence of carbon at
      the 5-position of tetrahydrofolate analogues is sufficient for inhibition of
      GARFT, that N-8 and the 2-amino group are involved in binding of DDATHF to GARFT,
      probably through hydrogen bonds, and that the structures of the phenyl ring and
      amino acid side chain of DDATHF analogues are not primary determinants of GARFT
      inhibition by monoglutamate forms of these compounds. We also conclude that
      polyglutamation plays a major role in the potent cytotoxicity of DDATHF.

PMID- 1993211
TI  - Involvement of a histidine residue in the interaction between membrane-anchoring
      protein (QPs) and succinate dehydrogenase in mitochondrial succinate-ubiquinone
      reductase.
AB  - The involvement of a histidine residue of the membrane-anchoring protein (QPs)
      fraction in reconstitution of succinate dehydrogenase to form succinate
      ubiquinone reductase is studied by using a histidine-modifying reagent,
      diethylpyrocarbonate (DEPC). A maximum inactivation of 80% of reconstitutive
      activity is obtained when QPs is treated with 1 mM DEPC at 0 degrees C for 30 min
      in 50 mM Tris-HCl (pH 7.0). DEPC also inactivates about 85% of intact succinate
      ubiquinone reductase. The inactivation of succinate-ubiquinone reductase by DEPC
      is a result of the modification of essential histidine residues of succinate
      dehydrogenase. The inactivation is not a result of the modification of the
      histidine residue in QPs which is essential for interaction with succinate
      dehydrogenase because the QPs dissociated from the inactivated succinate
      ubiquinone reductase is active in reconstitution with active succinate
      dehydrogenase. Apparently, the essential histidine in QPs is shielded by
      succinate dehydrogenase and thus inaccessible to DEPC modification in succinate
      ubiquinone reductase. The involvement of a histidine residue of QPs in
      interaction with succinate dehydrogenase is further evident by the presence of
      553 nm shoulder on the alpha-absorption peak of reduced cytochrome b-560 (a
      characteristic of physical association of QPs with succinate dehydrogenase) in
      the DEPC-inactivated succinate-ubiquinone reductase. This shoulder disappears
      from a mixture of succinate dehydrogenase and DEPC-treated QPs when reduced with
      dithionite. About one histidine residue per molecule of QPs is modified in the
      DEPC-treated sample, suggesting that only one histidine residue is essential for
      interaction with succinate dehydrogenase. This essential histidine group is
      located in the smaller subunit (Mr 13,000) of QPs.

PMID- 1993212
TI  - Molecular basis of chronic granulomatous disease.

PMID- 1993213
TI  - Recombinant human granulocyte-macrophage colony-stimulating factor in combination
      with standard induction chemotherapy in de novo acute myeloid leukemia.
AB  - Based on in vitro data suggesting that recombinant human granulocyte-macrophage
      colony-stimulating factor (rhGM-CSF) is capable of stimulating acute myeloid
      leukemia (AML) blast cells to become more sensitive to cell-cycle-specific drugs
      we conducted a phase I/II study in de novo AML patients (pts). rhGM-CSF (250
      micrograms/m2/d, continuous intravenous infusion) was administered in 18 pts
      suffering from de novo AML in combination with standard induction chemotherapy (3
      + 7 = daunorubicin 45 mg/m2 days 1 through 3, cytosine-arabinoside [Ara-C] 200
      mg/m2 continuous infusion days 1 through 7). GM-CSF was started 48 or 24 hours
      before chemotherapy (prephase) in 14 pts. In four pts with high white blood cell
      counts (WBC) rhGM-CSF was started after chemotherapy-induced cell reduction (WBC
      less than 30,000/mm3). During prephase GM-CSF induced an increase in neutrophil
      and blast cell counts in 13 of 14 and 10 of 14 pts, respectively. In vivo
      recruitment of leukemic cells into drug-sensitive phases of the cell cycle could
      be demonstrated by multiparameter cell-cycle analyses in peripheral blood (n = 7)
      and bone marrow (n = 4) specimens. On day 14, complete aplasia was evident in 17
      of 18 pts. GM-CSF was administered until recovery from chemotherapy-induced
      myelosuppression (absolute neutrophil counts, [ANC] greater than 500/mm3).
      Fifteen pts (83%) achieved complete remission, 12 did so with one cycle. A
      shorter duration of neutropenia was evident in these pts compared with historical
      controls (n = 39), (ANC greater than 500/mm3, day 22.5 +/- 3.4 v 25.2 +/- 3.7, P
      less than .05). Three pts achieved complete remission after a second cycle (same
      combination of rhGM-CSF and 3 + 7). Two pts died during bone marrow aplasia
      because of invasive pulmonary aspergillosis. Clinical side effects possibly
      related to GM-CSF, mainly fever, diarrhea, and weight gain were mild and
      tolerable (World Health Organization toxicity grade less than or equal to 2).
      Together, rhGM-CSF recruits kinetically quiescient AML cells in vivo to enter
      drug-sensitive phases of the cell cycle and promotes early myeloid recovery from
      aplasia after exposure to standard induction chemotherapy for AML.

PMID- 1993214
TI  - Monoclonal antibody-purged autologous bone marrow transplantation therapy for
      multiple myeloma.
AB  - Eleven patients with plasma cell dyscrasias underwent high-dose chemoradiotherapy
      and anti-B-cell monoclonal antibody (MoAb)-treated autologous bone marrow
      transplantation (ABMT). The majority of patients had advanced Durie-Salmon stage
      myeloma at diagnosis, all were pretreated with chemotherapy, and six had received
      prior radiotherapy. At the time of ABMT, all patients demonstrated good
      performance status with Karnofsky score of 80% or greater and had less than 10%
      marrow tumor cells. Eight patients had residual monoclonal marrow plasma cells
      and 10 patients had paraprotein. Following high-dose melphalan and total body
      irradiation (TBI) there were seven complete responses, three partial responses,
      and one toxic death. Granulocytes greater than 500/mm3 were noted at a median of
      21 (range 12 to 46) days posttransplant (PT) and untransfused platelets greater
      than 20,000/mm3 were noted at a median of 23 (12 to 53) days PT in 10 of the 11
      patients. Natural killer cells and cytotoxic/suppressor T cells predominated
      early PT, with return of B cells at 3 months PT and normalization of T4:T8 ratio
      at 1 year PT. Less than 5% polyclonal marrow plasma cells were noted in all
      patients after transplant. Three of the seven complete responders have had return
      of paraprotein, two with myeloma, and have subsequently responded to alpha 2
      interferon therapy. Eight patients are alive at 18.9 (8.9 to 43.1) months PT and
      four remain disease-free at 12.3, 17.5, 18.9, and 29 months PT. This preliminary
      study confirms that high-dose melphalan and TBI can achieve high response rates
      without unexpected toxicity in patients who have sensitive disease, and that MoAb
      based purging techniques do not inhibit engraftment. Although the follow-up is
      short- and long-term outcome to be determined, relapses post-ABMT in these
      heavily pretreated patients suggest that ABMT or alternative treatment strategies
      should be evaluated earlier in the disease course.

PMID- 1993215
TI  - Cyclosporine therapy for advanced Langerhans cell histiocytosis.
AB  - Prompted by evidence that Langerhans cell histiocytosis (LCH) is a nonmalignant
      disorder of immune regulation, we used cyclosporine (12 mg/kg/d orally) to treat
      three young children with advanced multisystem LCH. All three patients had
      partial responses to cyclosporine within 2 months of therapy, as evidenced by
      complete resolution of organ dysfunction and regression of the majority of
      lesions. Complete responses were attained by adding relatively nontoxic
      chemotherapy (ie, prednisone and vinblastine). Toxicity from cyclosporine
      comprised mild and reversible elevations of the serum creatinine and blood urea
      nitrogen. These results indicate that further evaluation of cyclosporine for the
      treatment of patients with advanced LCH is warranted.

PMID- 1993216
TI  - Comparative effects of thrombopoietin and interleukin-6 on murine
      megakaryocytopoiesis and platelet production.
AB  - A thrombocytopoiesis-stimulating factor (TSF or thrombopoietin) derived from
      human embryonic kidney (HEK) cells is known to increase platelet production and
      to increase the number of morphologically unrecognizable early megakaryocytes,
      ie, small acetylcholinesterase-positive (SAChE+) cells in mice. Other recent
      studies have concluded that interleukin-6 (IL-6) also stimulates murine
      megakaryocytopoiesis both in vitro and in vivo. Some workers have suggested that
      IL-6 is thrombopoietin. Therefore, the purpose of this study was to compare the
      effects of TSF and IL-6 on percent 35S incorporation into platelets, platelet
      sizes, and the percentages of SAChE+ cells in C3H mice, and to determine if they
      produce the same or different responses. The results showed that two or four
      injections of a partially purified TSF (total dose of 2 or 4 units (U) over a 1-
      or 2-day period) increased percent 35S incorporation into platelets (P less than
      .005) and platelet sizes (P less than .005) of both normal and rebound
      thrombocytotic mice when compared with values from other mice treated with human
      serum albumin, the carrier protein for both TSF and IL-6. In eight separate
      experiments, it was shown that IL-6 (40,000 U, 4 micrograms), when given to
      rebound-thrombocytotic mice in four injections over a 2-day period, produced a
      small but significant (P less than .005) increase in percent 35S incorporation
      into platelets. Additional studies showed that negative results were obtained
      when similar high doses of IL-6 were administered in two doses over a 1-day
      period. TSF, but not IL-6, stimulated an increase in platelet sizes of normal
      mice (P less than .005 to 0.0005); however, IL-6 increased platelet sizes of
      rebound-thrombocytotic mice when given in two of four injections (P less than .05
      to .0005). Also, IL-6, but not TSF, caused anemia in normal mice (P less than
      .0005) that were given two injections and tested 3 days later. TSF stimulated an
      increase (P less than .005) in the percentage of SA-ChE+ cells; whereas IL-6,
      even at high doses, did not. Because of the observed differences in biologic
      responses of these two cytokines, we conclude that TSF and IL-6 are separate
      entities.

PMID- 1993217
TI  - Effects of recombinant human macrophage colony-stimulating factor on plasma
      cholesterol levels.
AB  - Recombinant human macrophage colony-stimulating factor (rhM-CSF) is a
      hematopoietic growth factor that stimulates the growth, differentiation,
      proliferation, and activation of cells of the monocyte/macrophage lineage. rhM
      CSF was administered to rabbits and nonhuman primates to evaluate effects on
      cholesterol homeostasis. Decreases in plasma cholesterol concentrations were
      observed during rhM-CSF administration. The observed mean (+/- SD) decreases over
      a range of doses in nonhuman primates receiving rhM-CSF by continuous intravenous
      infusion (CIVI) or intravenous bolus (IVB) injection were approximately 16% +/-
      8% and 43% +/- 10%, respectively. Low-density lipoprotein (LDL) cholesterol
      levels decreased 55% +/- 9% from pretreatment baseline values in the animals
      receiving rhM-CSF by IVB. Normocholesterolemic New Zealand white rabbits
      receiving rhM-CSF over a range of doses by CIVI showed a decrease from baseline
      in total cholesterol of approximately 28% +/- 17%, with LDL cholesterol levels
      decreasing by approximately 72% +/- 33%, while high-density lipoprotein levels
      showed variable changes, including increased values. A decrease of 36% +/- 26% in
      total plasma cholesterol was observed in Watanabe Heritable Hyperlipidemic
      rabbits receiving rhM-CSF by CIVI for 7 days. This decrease was attributable
      almost entirely to decreases in LDL cholesterol, which fell approximately 34% +/-
      24% from baseline. Although the mechanism of this cholesterol-lowering effect is
      unknown, these results strongly suggest that rhM-CSF may provide a novel
      treatment for hypercholesterolemia and may be useful in investigations into the
      mechanisms of cholesterol homeostasis and atherogenesis.

PMID- 1993218
TI  - Developmental potential of hematopoietic stem cells determined using retrovirally
      marked allophenic marrow.
AB  - Genetic markers of two general types have been used to assess the number of
      simultaneously productive stem cells in vivo, retrovirus markers and enzyme or
      hemoglobin variants. Use of the two techniques has led to different conclusions
      regarding stem-cell population organization, kinetics, and usage. To better
      understand this discrepancy, we have combined the two methods by retrovirally
      marking and transplanting stem cell populations of allophenic mice in which all
      tissues, including the hematopoietic system, are chimeric. Hematopoietic and
      lymphoid tissues of engrafted recipients were analyzed by Southern blotting to
      determine the number and extent of participation of individually marked stem
      cells. Genotypic chimerism of the same tissues was determined by quantitating
      electrophoretic variants of glucose phosphate isomerase. This procedure permitted
      the genotypic identification of individual stem-cell clones. The results
      demonstrate the participation of few pluripotent stem cells in the repopulation
      and maintenance of engrafted hematopoietic and lymphoid tissues. Furthermore,
      stem cells used during the period of early engraftment tended to be of one
      genotype (DBA/2), whereas stem cells used for long-term maintenance tended to be
      of the other, coexistent genotype (C57BL/6). We propose that this genotypic
      specificity reflects functional differences in stem-cell subpopulations and their
      relative prevalence in different mouse strains suggests a genetic component in
      the organization and usage of stem cells.

PMID- 1993219
TI  - Immunologic detection of endothelial cells in human whole blood.
AB  - In this report we show that human endothelial cells (EC) can be detected in
      circulating blood by means of the EC-specific monoclonal antibody (MoAb)
      designated as CLB-HEC 19 and expressed quantitatively as number of cells per
      milliliter of whole blood. We first developed a method that was able to recover
      cultured human EC added to whole blood by Percoll density gradient
      centrifugation. The final recovery of the EC was 91.6% (SE = 0.65%). The EC were
      identified in the gradient subfractions by indirect immunofluorescence with the
      MoAb CLB-HEC 19. This method was then applied to the separation and
      characterization of EC or EC remnants from the whole arterial and venous blood
      taken from two groups of patients subjected to heart catheterization. Firstly, a
      preliminary blood screening of random samples was performed in a group of eight
      patients (group I) using a scoring evaluation for the presence of EC and the
      results were expressed as positivity index. Secondly, the complete blood
      screening of a group of ten patients (group II) was performed for the detection
      of immunofluorescent cells and the results were expressed as number of EC per
      milliliter of whole blood. Our results show in both group I and II a significant
      presence of EC in the blood after catheterization compared with their basal
      values. The minimal detectable concentration of EC was 0.06 cells/mL (SE = 0.057)
      of whole blood. We consider this technique as a suitable clinical test for the
      detection of EC injury in cardiovascular pathology.

PMID- 1993220
TI  - Macrophage colony-stimulating factor (CSF-1) gene expression in human T
      lymphocyte clones.
AB  - Macrophage colony stimulating factor (CSF-1) is one of several cytokines that
      control the differentiation, survival, and proliferation of monocytes and
      macrophages. A set of 11 human T-cell clones, chosen for their phenotypic
      diversity, were tested for their ability to express CSF-1 mRNA. After 5 hours of
      stimulation with phorbol myristate acetate (PMA) + calcium ionophore (Cal), all T
      cell clones expressed a major 4-kb transcript, a less abundant 2-kb transcript,
      and several other minor species. This pattern of expression is typical for CSF-1
      mRNAs. Furthermore, of the two alloreactive T-cell clones analyzed, only one
      showed a definitive message for CSF-1 on specific antigenic stimulation, but with
      delayed kinetics and less efficiency. Both conditions of stimulation induced the
      release of CSF-1 protein by T cells in the culture medium. Together, these
      findings demonstrate for the first time that normal T cells are able to produce
      CSF-1, previous reports being limited to two cases of tumoral cells of the T-cell
      lineage.

PMID- 1993221
TI  - Effect of tamoxifen on cell lines displaying the multidrug-resistant phenotype.
AB  - We examined the effect of tamoxifen (Tmx), verapamil, and daunorubicin (DNR) in
      two cell lines that displayed the multidrug-resistant (MDR) phenotype and used
      laser flow cytometry to quantitate intracellular DNR content. In the vinblastine
      resistant human lymphoblastic lymphoma cell line CEM-VBL, simultaneous incubation
      of DNR with Tmx 10 mumol/L or Tmx 50 mumol/L increased intracellular DNR
      fluorescence in a dose-dependent manner and demonstrated an uptake pattern
      similar to that seen with DNR and verapamil. Similar results were obtained in the
      vincristine-resistant human myeloid leukemia cell line HL-60/RV+. Cellular
      retention of DNR was also measured in both cell lines and results suggested that
      continuous exposure of the cells to Tmx resulted in higher intracellular DNR
      content compared with cells resuspended in fresh medium. No effect of Tmx or
      verapamil was observed in the drug-sensitive parent cell lines CEM or HL-60.
      Clonogenic experiments were then performed to determine whether Tmx was itself
      inhibitory to cell growth or whether Tmx potentiated DNR cytotoxicity. Tmx 10
      mumol/L did not significantly inhibit either CEM-VBL or HL-60/RV+ cells after a 3
      hour exposure followed by culture in methylcellulose. Tmx 50 mumol/L was
      significantly more inhibitory in both cell lines. However, cells that had been
      incubated with DNR and Tmx 10 mumol/L demonstrated a marked increment in growth
      inhibition compared with cells that had been incubated with DNR alone or Tmx 10
      mumol/L alone. Based on the data presented here, we suggest that clinical testing
      of Tmx and DNR be pursued in the setting where MDR may play a role.

PMID- 1993222
TI  - Inactivation of the retinoblastoma gene in human lymphoid neoplasms.
AB  - The absence of wild type retinoblastoma (Rb) gene expression in a wide variety of
      human solid tumors suggests an etiologic role for this tumor suppressor gene in
      human cancer. We have evaluated the involvement of Rb gene inactivation in the
      pathogenesis and progression of human lymphoma and leukemia. We examined the
      genomic configuration and transcription of the Rb gene in cultured cell lines and
      primary cases of T- and B-cell lymphomas and leukemias. By Southern analysis,
      abnormalities of the Rb locus were identified in 1 of 5 T-cell acute
      lymphoblastic lymphoma (T-ALL) cell lines, 1 of 26 primary cases of T-ALL, 1 of
      40 primary cases of chronic lymphocytic lymphoma/well-differentiated lymphoma
      (CLL/WDL), and 1 of 15 primary cases of intermediately differentiated lymphoma
      (IDL). By Northern analysis, markedly reduced or abnormal expression of the Rb
      gene was identified in 2 of 5 T-ALL cell lines, 1 of 7 primary cases of T-ALL, 1
      of 5 primary cases of CLL/WDL, and 1 of 6 primary cases of IDL. These findings
      show that Rb gene inactivation can be associated with a broad range of lymphoid
      neoplasms and that loss of the tumor suppressor function of Rb may influence the
      pathogenesis and progression of lymphoma/leukemia.

PMID- 1993223
TI  - Transmembrane mobility of phospholipids in sickle erythrocytes: effect of
      deoxygenation on diffusion and asymmetry.
AB  - We studied the effect of sickling on the transmembrane reorientation and
      distribution of phospholipids in the red blood cells of patients homozygous for
      sickle cell anemia (SS). To this purpose, we followed the redistribution kinetics
      of trace amounts of spin-labeled analogues of natural phospholipids first
      introduced in the membrane outer leaflet of normal or sickle erythrocytes exposed
      to air or nitrogen. Deoxygenation had no effect on the lipid redistribution
      kinetics in normal (AA) cell membranes. At atmospheric pO2, unfractionated SS
      cells were not different from normal cells. However, on deoxygenation inducing
      sickling, phosphatidylcholine passive diffusion was accelerated and the rate of
      the adenosine triphosphate-dependent transport of aminophospholipids was reduced,
      especially for phosphatidylserine. The stationary distribution of the
      aminophospholipids between the two leaflets was slightly less asymmetric, a
      phenomenon more pronounced with phosphatidylethanolamine. These changes were
      rapidly reversible on reoxygenation. When SS cells were separated by density,
      both dense and light cells exhibited the properties cited above. However, dense
      cells exposed to air possessed a lower aminophospholipid transport rate. These
      data favor the relationship between aminophospholipid translocase activity and
      phospholipid transmembrane asymmetry. Sickle cell disease is the first case of
      aminophospholipid translocase pathology.

PMID- 1993224
TI  - The beta globin 3' enhancer element confers regulated expression on the human
      gamma globin gene in the human embryonic-fetal erythroleukemia cell line K562.
AB  - We have constructed fusion genes comprised of gamma and beta globin elements and
      globin sequences linked to neomycin resistance (neoR) genes to define the cis
      acting sequences responsible for developmental stage-specific expression and
      induction of fetal globin genes in embryonic-fetal erythroleukemia K562 cells.
      The results indicate that the gamma promoter is required for proper initiation of
      transcription. However, the accumulation of gamma globin transcripts in response
      to hemin induction requires the additional presence of either gamma intervening
      sequence 2 or the 3' enhancer element of the beta globin gene. Thus, the gamma
      promoter may provide the elements for developmental stage-specific gene
      expression during fetal life. By contrast, the beta 3' enhancer is erythroid
      specific but not developmental stage- or gene-specific.

PMID- 1993225
TI  - Detection of residual leukemia after bone marrow transplant for chronic myeloid
      leukemia: role of polymerase chain reaction in predicting relapse.
AB  - We used the polymerase chain reaction (PCR) to detect residual leukemia-specific
      mRNA in blood and marrow from 37 patients in complete hematologic and cytogenetic
      remission after allogeneic bone marrow transplant (BMT) for chronic myeloid
      leukemia (CML). Our two-step PCR method involved the use of "nested primers" in
      the second step and could detect one K562 cell diluted into 10(5) normal cells.
      Elaborate measures were taken to exclude false-positive and false-negative
      results. In nine patients whose blood and marrow were studied simultaneously the
      results were concordant (two positive and seven negative). Twenty-three patients
      transplanted in chronic phase (CP) with unmanipulated donor marrow were studied.
      Blood cells from nine of these patients were studied 3 to 6 months post-BMT and
      six were PCR positive; three were negative on subsequent studies. Blood cells
      from 18 patients studied between 8 months and 8 years post-BMT were all PCR
      negative. Nine patients transplanted in CP with T-cell-depleted marrow cells were
      studied. Blood from five was positive 3 to 24 months post-BMT; blood from five
      was negative 3 to 6 years post-BMT. Four patients no longer in first CP were
      studied after BMT with unmanipulated donor marrow. Blood from all four was
      positive 5 to 19 months post-BMT. Based on the known clinical results of
      transplant in these three cohorts we conclude that PCR may be positive within 6
      months of BMT in patients who can expect long-lasting remission, whereas PCR
      positivity later after BMT may indicate that the probability of cure is reduced.
      Thus, the technique may prove useful for early assessment of new transplant
      protocols that might inadvertently increase the risk of relapse.

PMID- 1993226
TI  - Rapid simultaneous detection of multiple retroviral DNA sequences using the
      polymerase chain reaction and capillary DNA chromatography.
AB  - The polymerase chain reaction (PCR) technique is a powerful new tool for
      amplifying target DNA, thus allowing for sensitive detection of specific nucleic
      acid sequences. One important potential use of PCR involves screening the donated
      blood supply for transfusion-transmitted viruses. Realization of this goal has
      been limited by (1) the requirement for multiple, discrete PCR reactions to
      amplify and detect target sequences of more than one virus, and (2) the lack of a
      rapid, nonhazardous means for specific detection of one or more PCR-amplified
      products. We report the simultaneous amplification of three distinct target
      sequences without discernable loss in sensitivity toward any single target
      sequence. We also demonstrate very rapid separation and detection of PCR
      amplified viral DNA through the use of automated capillary DNA chromatography.
      Amplified DNA peaks were initially identified by scanning the capillary effluent
      at ultraviolet wavelengths, while discrimination of human immunodeficiency virus
      type 1 and human T-cell leukemic virus type I PCR-amplified DNA was accomplished
      through use of virus-specific, fluorescently labeled primers and probes. These
      results indicate progress toward an automated system for screening the blood
      supply for nucleic acid sequences of multiple pathogens.

PMID- 1993227
TI  - Detection of early human T-cell lymphotropic virus type I antibody patterns
      during seroconversion among transfusion recipients.
AB  - From a cohort of human T-cell lymphotropic virus type I (HTLV-I) exposed
      transfusion recipients (N = 71) enrolled in the Jamaican Transfusion Study, 11
      were selected for detailed laboratory evaluation. All recipients were followed at
      monthly intervals for 6 months and then bimonthly up to 1 year for evidence of
      HTLV-I seroconversion. Without regard to results on screening assays,
      pretransfusion and posttransfusion samples were tested with two licensed HTLV-1
      whole-virus screening enzyme immunoassays (EIAs), recombinant EIAs for antibody
      against tax (p40x) and p21e envelope, standard whole virus Western blot (WB), WB
      enhanced with recombinant p21e, and radioimmunoprecipitation assay (RIPA). In the
      early period posttransfusion, antibody to gag core protein was predominant with
      anti-p24 generally appearing before anti-p19. Recombinant anti-p21e envelope
      protein, in EIA and WB format, was frequently the earliest envelope reactivity
      detected, while anti-gp46 in WB and anti-gp61/68 in RIPA system appeared later.
      Anti-tax antibodies appeared later in the time course of seroconversion. The
      whole-virus EIAs were less sensitive than the confirmatory assays. The
      combination of WB and RIPA or WB enhanced with recombinant p21e appeared equally
      effective in confirming samples as positive by the Public Health Service two gene
      group confirmatory algorithm. However, specificity of this assay approach could
      not be addressed in this study.

PMID- 1993228
TI  - Late results and current indications of latissimus dorsi breast reconstructions.
AB  - One hundred and fifty latissimus dorsi flaps were used in 145 patients out of a
      series of 483 breast reconstructions performed from 1977 to 1988. There were few
      immediate complications and a durable, good cosmetic result was obtained in two
      thirds of the 103 cases reviewed after at least one year. The main reasons for
      dissatisfaction with long-term results were capsular contracture (grades III and
      IV) and upper displacement of the implant. The rate of these late complications
      was 30%, the same as found in the simpler subpectoral reconstruction. However,
      prostheses with a thick outer envelope induced only 10% of severe capsular
      contracture. Reconstructions with autologous tissue are currently replacing
      latissimus dorsi flap reconstructions unless local or general conditions
      contraindicate such major surgery or when the patient lacks motivation.

PMID- 1993229
TI  - The treatment of donor sites with cultured epithelial grafts.
AB  - In a significant number of elderly patients, the healing of split skin donor
      sites can be delayed. The cultured allogenic epithelial graft (CAG) has been
      reported to heal leg ulcers. The mechanism of action may be to improve the
      healing environment and thus stimulate the host skin cells. A clinical trial was
      undertaken to compare the healing rate of the donor sites of elderly patients
      using CAGs and two commercially available dressings. Compared to Jelonet, CAGs (p
      = 0.008) and OpSite (p = 0.013) significantly reduced the number of patients with
      delayed healing. There was no significant difference between CAGs and the
      occlusive dressing, OpSite.

PMID- 1993231
TI  - Pulse oximetry in postoperative monitoring of free muscle flaps.
AB  - The use of a pulse oximeter for monitoring free muscle transfers is described.
      Three cases are presented, two of which were uncomplicated and one in which the
      need for revision of anastomosis was identified by the oximeter. Observations on
      a pedicled muscle flap are also reported. Pulse oximeters provide an improved
      photoplethysmographic monitoring technique which is easily performed using
      completely standard operating theatre equipment.

PMID- 1993230
TI  - An arterialised venous flap using the long saphenous vein.
AB  - Free arterialised venous flaps and an arterialised osteocutaneous venous flap,
      fed by an arterialised long saphenous vein, were used successfully in three
      cases. This flap has a larger skin territory than those previously reported and
      the incorporation of bone into such a flap has not been reported before.

PMID- 1993232
TI  - The distally-based brachioradialis muscle flap.
AB  - We describe the brachioradialis muscle flap based distally on the radial artery.
      It is quickly raised and provides excellent cover for soft tissue defects of the
      hand. In the two clinical cases the brachioradialis tendon has also been used for
      extensor tendon reconstruction.

PMID- 1993233
TI  - The dartos musculocutaneous flap.
AB  - Six dartos musculocutaneous flaps have been used to resurface proximal penile
      defects. The vascular anatomy of the flap, surgical technique and complications
      are described in detail.

PMID- 1993234
TI  - Medial fasciocutaneous flap of thigh for release of post-burn groin contractures.
AB  - Post-burn groin contractures, though uncommon, cause some patients distressing
      symptoms which are difficult to treat. Recurrence of contracture and symptoms is
      common and multiple operations are often required to control symptoms. We
      describe the use of the medial thigh fasciocutaneous flap for release of these
      contractures. Six flaps have been raised in four patients and symptomatic relief
      has been excellent in three. There have been no contracture recurrences.

PMID- 1993235
TI  - Pain and forehead expansion.
AB  - Tissue expansion of the forehead by intermittent bolus injection in three
      patients was noted to be extremely painful. This stimulated a prospective study
      in four patients whose discomfort was found to be related to a sharp rise in
      intraluminal pressure after bolus inflation. Tolerable infusion volumes were
      small (mean 6.25 cc) and associated with high pain scores (mean 7/10). Adequate
      expansion was protracted (mean 45 1/2 days) and was limited by pain. To eliminate
      the sharp rises in pressure associated with expansion by bolus injection, a
      syringe pump was used in two further inpatients. Adequate expansion was both
      quicker (mean 8.5 days) and less painful (mean pain score 2.6/10).

PMID- 1993236
TI  - Double lumen free jejunal transfer for reconstruction of the entire floor of
      mouth, pharynx and cervical oesophagus.
AB  - In those patients requiring proximal extension of a laryngopharyngectomy to
      include resection of the base of the tongue, there is a considerable mismatch
      between the circumference of the superior pharyngeal defect and a conventional
      jejunal conduit. An inverted J-shaped jejunal funnel can be prefabricated to
      enlarge the proximal stoma of a free jejunal transfer to overcome this size
      discrepancy and so prevent the high incidence of postoperative fistulae at the
      proximal anastomosis. In the most extreme case it will allow reconstruction of
      the entire floor of the mouth, pharynx and cervical oesophagus.

PMID- 1993237
TI  - Separation of the Baragwanath craniopagus twins.
AB  - A case of craniopagus twins is presented. Large contralateral flaps were used to
      cover the bony defect and exposed brain. Details of the planning and problems are
      discussed.

PMID- 1993238
TI  - Preoperative non-surgical over-correction of cleft lip nasal deformity.
AB  - Alar cartilage, which is elastic like auricular cartilage, is correctable in the
      early neonatal period. Taking advantage of this correctability, we have performed
      preoperative non-surgical over-correction for cleft lip nasal deformity of
      incomplete and complete cleft lips with a Simonart's band. The device for this
      correction was made by processing a nostril retainer into a nostril over
      corrector which utilises a spring of silicone rubber, works like a tissue
      expander and is supported by the nostril floor. Twenty cases are reviewed whose
      follow-up lasted more than 19 months. The earlier the non-surgical over
      correction began, the more satisfactory were the results that were obtained.

PMID- 1993239
TI  - The propeller flap method.
AB  - We report a method of elevating and rotating a flap, like a propeller, for the
      release of scar contractures. We have obtained satisfactory results in the repair
      of scar contractures in the cubital and axillary regions. This flap may be
      applied to the flexor side in other regions, for example the groin, popliteal
      fossa and fingers where burn contractures are common.

PMID- 1993240
TI  - Calcium alginate as a dressing for mini skin grafts (skin soup).

PMID- 1993241
TI  - Free vascularised epiphyseal transfer designed on the reverse anterior tibial
      artery.
AB  - This report describes a case of radial club hand which was reconstructed by a
      proximal growth plate of the fibula supplied by the reverse anterior tibial
      artery. A brief discussion on epiphyseal transfer of the fibula is included.

PMID- 1993242
TI  - Survival of a free radial forearm flap without venous return.
AB  - The radial forearm free flap is an ideal transfer for intraoral reconstruction
      because of its large vessels and pliable nature. In the case presented, a
      proximally-based forearm flap was transferred for reconstruction of an intraoral
      defect in the buccal and retromolar region after carcinoma resection, but there
      was no venous flow from either cephalic vein or venae comitantes following
      completion of the arterial anastomosis. In order to reduce the congestion in the
      flap, an end-to-end anastomosis between the distal end of the radial artery and
      the ipsilateral lingual vein was performed. Despite the absence of venous return,
      flap survival was complete.

PMID- 1993243
TI  - Plastic surgery audit codes: are the results reproducible?
AB  - The effective coding of data to produce a medical audit relies on agreement
      between the coders. This study was designed to assess whether coders can agree on
      codes for diagnosis and operations in a plastic surgery unit. Information from 50
      patients was presented to a panel of six coders who were required to code the
      data using the International Classification of Diseases (ICD-9) and the Office of
      Population Census Studies (OPCS-4) systems. The results show that agreement
      between all the panellists occurred in only 32 out of 50 patients for one
      diagnostic code and 30 out of 50 for one operation code. When a patient had more
      than one diagnosis or operation, agreement was very much worse. Expert coders
      produced better results than the medical coders. The results are discussed with
      reference to other coding systems.

PMID- 1993244
TI  - Video assessment of surgical technique.
AB  - The surgical technique of nine trainee surgeons, as recorded on videotape, was
      evaluated under five headings using a scoring system and the results were
      discussed with them. Six of the trainees were assessed on more than one occasion
      during their training. All trainees felt that they had benefited from the
      assessment.

PMID- 1993245
TI  - The use of a wire frame to fix grafts externally.
AB  - We have shown the effectiveness of using externally attached frames made of
      Kirschner wires in fixing grafts. The technique has proved to be useful for
      securing grafts to graft beds and it has prevented the edges of the grafts from
      lifting. With simple materials and a simple technique, the tie-over method
      combined with external wire frames has brought about better results in sheet skin
      grafting.

PMID- 1993246
TI  - Subclavicular approach in head and neck reconstruction with the latissimus dorsi
      musculocutaneous flap.
AB  - As an alternative procedure in transferring the pedicled latissimus dorsi
      musculocutaneous flap to the head and neck, we have devised a subclavicular
      approach and applied it successfully in our clinic. This approach reduces the
      distance of the transfer and leaves no bulkiness over the clavicle. The
      subclavian vessels, the brachial plexus and the cervical pleura are retracted
      safely beyond the periosteum during the procedure, and the pedicle of the flap is
      protected under the clavicle postoperatively.

PMID- 1993247
TI  - The immunology of tolerance and autoimmunity.

PMID- 1993249
TI  - The use of class II MHC binding peptides in immunotherapy.

PMID- 1993248
TI  - Peptide interactions with MHC class II molecules.

PMID- 1993250
TI  - Unresolved questions in clinical T cell vaccination.

PMID- 1993252
TI  - Heterogeneity of T cell repertoires in human autoimmune disease.

PMID- 1993251
TI  - Immunization with T cell receptor peptides.

PMID- 1993253
TI  - T cell vaccination in rheumatoid arthritis.

PMID- 1993254
TI  - The immunopathogenesis of rheumatoid arthritis.

PMID- 1993255
TI  - Monoclonal antibody treatment of rheumatoid arthritis.

PMID- 1993256
TI  - Genetically engineered monoclonal antibodies.

PMID- 1993257
TI  - Oral tolerance and collagen arthritis.

PMID- 1993258
TI  - The cytokine network in rheumatoid arthritis.

PMID- 1993259
TI  - Immunosuppressive and long-acting anti-inflammatory activity of mycophenolic acid
      and derivative, RS-61443.

PMID- 1993260
TI  - Pharmacology of rapamycin: a new immunosuppressive agent.

PMID- 1993261
TI  - A pitfall in the diagnosis of supernumerary kidney.

PMID- 1993262
TI  - Nephrogenic adenoma of the renal pelvis.

PMID- 1993263
TI  - Urinary obstruction due to labial fusion.

PMID- 1993265
TI  - Transitional cell carcinoma arising in a urachal cyst.

PMID- 1993264
TI  - Vulvar and vaginal implantation of transitional cell carcinoma of the urinary
      tract.

PMID- 1993266
TI  - Stuttering priapism in sickle cell disease.

PMID- 1993267
TI  - Carcinosarcoma of the bladder.

PMID- 1993268
TI  - Wegener's granulomatosis presenting as prostatitis.

PMID- 1993269
TI  - Removal of ureteric stents with a flexible cystoscope.

PMID- 1993270
TI  - Management of staghorn stones using a combination of lithotripsy, percutaneous
      nephrolithotomy and Solution R irrigation.
AB  - The treatment of staghorn and partial staghorn calculi remains complex despite
      modern methods of stone removal. We describe the results following treatment of
      112 stones. Three methods were used: percutaneous nephrolithotomy, extracorporeal
      shockwave lithotripsy and Solution R irrigation, either alone or in combination;
      57 stones (55.8%) were completely cleared, with Solution R irrigation helping to
      achieve complete clearance in 6 of these. A further 24 stones were not completely
      cleared (small asymptomatic fragments less than 3 mm remained). A satisfactory
      outcome (stone-free or asymptomatic fragments less than 3 mm) was achieved in 81
      stones (79%).

PMID- 1993271
TI  - The impact of extracorporeal piezoelectric lithotripsy on the management of
      ureteric calculi: an audit.
AB  - The presentation and management of 153 patients with ureteric calculi requiring
      active treatment over a 12-month period were reviewed; 74% of patients had
      primary ureteric calculi and 26% had ureteric calculi composed of fragments
      resulting from extracorporeal piezoelectric shockwave lithotripsy (EPL) to renal
      calculi; 32 patients (21%) had more than 1 calculus or a steinstrasse. The
      primary procedures included were in situ EPL (n = 54), push-bang (44), retrograde
      ureteroscopy (40), Dormia basket extraction (6), push-pull (1), antegrade
      ureteroscopy (1) and combinations of these (7). The success of the primary
      procedure could not be predicted from stone size, site or duration in the ureter,
      but upper tract dilatation was significantly less (p less than 0.01) in the
      successful group. The overall success rate for complete stone extraction was 97%,
      but 54 patients (35%) required more than 1 procedure to achieve this. In situ EPL
      and push-bang, as either primary or secondary procedures, were successful in
      treating 79 patients (52%); 2 patients required ureterolithotomy (1.3%). The
      overall complication rate was 18%. Since EPL is only successful in treating
      approximately half of ureteric calculi, a range of other treatments should be
      available to maintain a low rate of open surgery.

PMID- 1993272
TI  - Do extracorporeal shock waves affect urinary excretion of glycosaminoglycans?
AB  - Urinary excretion of glycosaminoglycans (GAGs) was studied in 9 anaesthetised
      dogs and 10 patients with single kidneys. The animals were studied for 4 to 5
      hours after administration of shock waves to 1 kidney, the contralateral organ
      serving as control. Urinary excretion of GAGs was measured on both sides. The
      patients were studied 0 to 24 and 32 to 56 h after extracorporeal shock wave
      lithotripsy (ESWL). In the animals an increased mean urinary excretion of GAGs
      was observed on both sides; this was more marked in the treated kidney. The
      increase reflects tissue injury in the exposed kidney induced by the
      extracorporeal shock waves. No increase in mean urinary excretion of GAGs was
      observed in the patients.

PMID- 1993273
TI  - Upper tract tumours following cystectomy for bladder cancer. Is routine
      intravenous urography worthwhile?
AB  - The incidence and presentation of upper tract tumours were studied in 180
      patients who had previously undergone cystectomy for transitional cell carcinoma
      of the bladder. Intravenous urography was performed routinely 3 months after
      cystectomy, 1 year later and at 3-yearly intervals thereafter. Ten patients
      developed upper tract tumours; 1 presented with loin pain and the remainder with
      haematuria. Six patients underwent nephroureterectomy and 5 of them lived for at
      least 4 years; 4 were inoperable and only 1 survived longer than 6 months. In
      this series, all patients with upper tract tumours presented with symptoms and
      routine intravenous urography failed to detect any asymptomatic lesions. Routine
      radiological assessment of the upper tracts to detect tumours is not justified
      following cystectomy.

PMID- 1993274
TI  - Transitional cell carcinoma of the upper urinary tract: prognostic variables and
      post-operative recurrences.
AB  - In a retrospective study of 198 patients with transitional cell carcinoma of the
      upper urinary tract, post-operative recurrences developed as contralateral
      tumours in 2.5%, in the ureteric stump after conservative resection in 19% and in
      the bladder in 36.4%. Upper tract recurrences resembled the primary tumours in
      terms of grade and stage; of the bladder tumours, 89% were similar in grade and
      72% similar in stage to the primary tumours. Age, sex, grade and stage had no
      effect on the number of bladder recurrences, but ureteric tumours had
      significantly more recurrences than renal pelvicaliceal tumours. Sex, bladder
      recurrences and site of primary tumours did not influence survival. Thus grade
      and stage of the primary tumour were the only predictive variables of the final
      outcome.

PMID- 1993275
TI  - Night studies for primary diurnal and nocturnal enuresis and preliminary results
      of the "clam" ileocystoplasty.
AB  - Modified conventional urodynamic apparatus was used to provide overnight
      monitoring of bladder and rectal pressure. A group of 26 patients with primary
      diurnal and nocturnal enuresis underwent both daytime rapid fill cystometry and
      overnight natural fill cystometry. The overnight study was effective in detecting
      detrusor instability in 10 patients deemed normal on rapid fill cystometry; 6 of
      these have now undergone clam ileocystoplasty and 5 are dry; 3 are awaiting this
      procedure. The clam remains very effective in the management of patients with
      resistant nocturnal and diurnal enuresis if careful selection is adopted.
      Overnight cystometry has proved to be an invaluable adjunct to the investigation
      of patients with primary diurnal and nocturnal enuresis previously felt to be
      urodynamically normal.

PMID- 1993276
TI  - Is voided urine suitable for flow cytometric DNA analysis?
AB  - Samples of bladder washings are frequently used to provide cellular material for
      flow cytometric DNA analysis. Since voided urine is a potential source of similar
      material, the aim of this study was to determine whether voided urine yields
      satisfactory specimens. We compared the qualitative results of flow cytometric
      DNA analysis of the cells in 53 specimens of voided urine and 109 samples of
      bladder washings; 45% (24/53) of urine specimens gave satisfactory DNA histograms
      compared with 93% (101/109) of bladder washings. This difference was apparent
      regardless of whether the bladder contained a tumour. It was concluded that
      bladder washings provide superior material for flow cytometric DNA analysis and
      that flow cytometric DNA analysis of freshly voided urine may have deficiencies
      which preclude its use in routine clinical practice.

PMID- 1993278
TI  - Radical radiation treatment of invasive and locally advanced bladder carcinoma in
      elderly patients.
AB  - A total of 146 patients with invasive or locally advanced carcinoma of the
      bladder (T2-T4) underwent radiation treatment. A significantly higher complete
      response rate was observed with doses equal to or above 55 Gy and with doses
      corresponding to cumulative radiation effect (CRE) values of 1700 radiation
      effect units (reu) or more. In multivariate analysis, decreasing time from the
      first diagnosis of bladder carcinoma to radiation treatment and 1 or more
      transurethral resections was associated with a significant increase in survival;
      increases in T category and sedimentation rate were negative prognostic factors.
      Although both radiation dose and CRE levels had a significant effect on survival
      in univariate analysis, an increase in CRE levels alone was associated with a
      significant increase in survival in multivariate analysis. However, the most
      important predictor of survival was whether the patient showed a complete local
      response or not. This study emphasises the importance of treating patients with
      an adequate radiation dose over a short period of time in order to achieve the
      maximum radiobiological effect and thereby increase the possibility of cure.

PMID- 1993277
TI  - Clinical significance of the "palpable mass" in patients with muscle-infiltrating
      bladder cancer undergoing cystectomy after pre-operative radiotherapy.
AB  - Between 1976 and 1985, 132 patients with T2/T3/T4a bladder cancer underwent
      cystectomy after pre-operative radiotherapy (46 Gy: 67 patients; 20 Gy: 65
      patients). After a median time of 41 months, 62 patients were alive; 51 had died
      from recurrent bladder cancer and 19 from intercurrent disease without recurrence
      of their malignancy. Distant metastases developed in 40 patients, accompanied in
      5 cases by local recurrence. Local recurrence was the first sign of relapse in 11
      patients. In 3 patients the localisation of the relapse remained unknown. The
      corrected 5-year survival rate was 60%. T category and a palpable bladder tumour
      were independent pre-treatment prognostic factors in a Cox regression analysis,
      together with the interval between initial diagnosis and cystectomy. The presence
      of a palpable tumour before the start of treatment was associated with a
      particularly poor prognosis in T3/T4a tumours, whereas the survival of patients
      with non-palpable T3/T4a tumours was similar to that of patients with T2 bladder
      cancer. Another important prognostic factor was post-irradiation stage reduction
      (no residual muscle infiltration in the cystectomy specimen). Significantly more
      patients with non-palpable bladder tumours experienced post-radiation stage
      reduction than did those with a palpable tumour. However, the prognostic value of
      stage reduction was statistically significant only in patients with palpable
      bladder tumours.

PMID- 1993279
TI  - Adjuvant topical chemotherapy versus immunotherapy in primary superficial
      transitional cell carcinoma of the bladder.
AB  - In a prospective randomised controlled study, the efficacy of ethoglucid was
      compared with that of keyhole-limpet haemocyanin (KLH) in preventing recurrent
      tumours following transurethral resection of primary superficial transitional
      cell carcinoma of the bladder. Patients treated with ethoglucid (n = 39) received
      0.565 g (1% solution) ethoglucid weekly for 6 weeks and then monthly for 1 year.
      Patients treated with KLH (n = 38) were immunised subcutaneously with 1 mg KLH;
      bladder instillations of 30 mg were then given weekly for 6 weeks and thereafter
      monthly for 1 year. The recurrence rates, disease-free intervals and tumour
      progression rates were evaluated. The end-point of the study was either
      progression in stage or grade or more than 1 recurrence during the observation
      period. The minimum length of follow-up was 1 year. The recurrence rates, mean
      disease-free intervals and progression rates in the 2 groups showed no
      statistically significant differences.

PMID- 1993280
TI  - Quantitative analysis of the accuracy of linear array transrectal ultrasound in
      measurement of the prostate.
AB  - In 61 prostate autopsy specimens, linear array transrectal ultrasound and
      electronic vernier calipers were used to measure 3 maximal diameters along the
      longitudinal, anterior-posterior and transverse axes. The results were
      comparable. We assessed the reliability of empirical formulae, derived from
      various combinations of these 3 diameters, for the prediction of prostatic volume
      and weight. Formulae using all 3 diameters were accurate. The combination of
      longitudinal and anterior-posterior diameters, which was used clinically for
      prostate measurement, was less accurate.

PMID- 1993281
TI  - Activation of complement, kallikrein-kinin, fibrinolysis and coagulation systems
      by urinary catheters. Effect of time and temperature in biocompatibility studies.
AB  - Urethral strictures induced by the use of latex catheters and combined
      silicone/latex catheters following open-heart surgery have been reported. These
      strictures differ from the post-catheterisation type in affecting a greater
      length of urethra. Recently it was shown that complement was activated by
      catheters which cause inflammation, in contrast to clinically silent catheters.
      The present study was designed to investigate a possible association between
      catheter-induced inflammation and activation of another mediator of inflammation,
      the contact system. We also investigated various in vitro conditions to optimise
      biocompatibility studies. Our data indicate that both the complement and the
      kallikrein-kinin system are activated by potentially harmful silicone/latex
      catheters and may be involved in the pathophysiology of catheter-induced urethral
      strictures. In vitro biocompatibility tests may be performed at both 20 and 37
      degrees C. Glass test tubes may be used for in vitro complement but not for
      kallikrein-kinin investigations.

PMID- 1993282
TI  - First UK consensus conference on lithotriptor terminology--1989.
AB  - Recommended definitions to be used in the reporting of results of lithotripsy
      treatment are presented. It is suggested that these are the minimum requirements
      for reporting such treatment.

PMID- 1993283
TI  - Vasal injuries during childhood and their effect on subsequent fertility.
AB  - Thirty subfertile males had testicular obstruction following inguinal or pelvic
      surgery in childhood. All 13 patients with bilateral obstruction were azoospermic
      and 6 had developed antibodies to spermatozoa. Of 17 patients with unilateral
      obstruction, 11 had oligozoospermia and 6 had normal sperm counts: all had high
      titres of antibodies to spermatozoa (a significant difference from the men with
      bilateral obstruction). This indicates that male infertility can result from
      vasal or epididymal injuries in childhood due either to the obstruction itself or
      its immunological consequences. Following corrective surgery and prednisolone
      treatment for the antibodies, where appropriate, 5/17 patients with unilateral
      blocks and 1/11 with bilateral blocks successfully produced pregnancies.

PMID- 1993284
TI  - Outcome of antenatally diagnosed pelviureteric junction hydronephrosis.
AB  - Over a 6-year period, in a series of 107 consecutive patients with antenatally
      detected urological anomalies, 45 had pelviureteric junction (PUJ) hydronephrosis
      (66 units). Of these, 24 units (36%) had obstructive (group I) and 42 (64%) non
      obstructive hydronephrosis (group II). Significantly compromised renal function
      was found only in group I. Treatment in group I was by an early pyeloplasty; in
      group II the patients were kept under close review. During the 6-year period, 2
      units (5%) in group II, deteriorated, 13 (31%) improved and 27 (64%) were
      unchanged. These results suggest that early in life, antenatally diagnosed PUJ
      hydronephrosis without obstruction may be a relatively benign condition but will
      require long-term follow-up in order to determine the natural history of the
      condition.

PMID- 1993285
TI  - Informed consent to HIV antibody testing.

PMID- 1993286
TI  - The Bristol regimen for cancer patients.

PMID- 1993287
TI  - Why are there so many injuries? Why aren't we stopping them?

PMID- 1993288
TI  - History of medicine lectures at McGill.

PMID- 1993289
TI  - Periodic health examination, 1991 update: 1. Screening for cognitive impairment
      in the elderly. Canadian Task Force on the Periodic Health Examination.

PMID- 1993290
TI  - Iron deficiency anemia in the elderly: the diagnostic process.
AB  - OBJECTIVE: To determine the effectiveness of physician probability estimates
      calculated on the basis of findings from history-taking and physical examination
      in the diagnosis of iron deficiency anemia in elderly patients. DESIGN:
      Prospective study. SETTING: Two community hospitals offering secondary and
      tertiary care. PATIENTS: A total of 259 patients over 65 years of age found to
      have previously undiagnosed anemia. MEASURES: Physician estimates of the
      likelihood of iron deficiency before (pretest probability) and after (post-test
      probability) the laboratory test results were available. The hemogram was
      available to the physicians when they made their pretest probability estimates.
      Because the serum ferritin level proved to be the most powerful of the laboratory
      test results studied, the likelihood ratios associated with the post-test
      estimates were compared with the ratios associated with the serum ferritin level.
      MAIN RESULTS: The post-test probability estimates were influenced by the serum
      ferritin level and the pretest estimates. The post-test estimates derived from
      the findings obtained through history-taking and physical examination and the
      laboratory test results (including the serum ferritin level) were slightly less
      accurate in predicting iron deficiency than the serum ferritin level alone.
      Nevertheless, a model in which the pretest estimates were used in addition to the
      serum ferritin level to predict iron deficiency proved to be more powerful than
      the serum ferritin level alone (p = 0.006). This indicated that the limitations
      of the post-test estimates were due to a misinterpretation of the serum ferritin
      level and that the findings from history-taking and physical examination added
      important diagnostic information. CONCLUSIONS: Physicians must be aware of test
      properties to provide optimal care to their patients. If test results are
      properly interpreted, pretest probabilities derived from findings obtained
      through history-taking and physical examination can add useful information that
      will lead to more accurate diagnoses.

PMID- 1993291
TI  - Early pregnancy assessment with transvaginal ultrasound scanning.
AB  - OBJECTIVE: To establish normal parameters in early pregnancy through transvaginal
      ultrasonography so that gestational age can be determined and to correlate the
      sonographic findings with serum human chorionic gonadotropin (hCG) levels
      calibrated against the first international reference preparation standard.
      SETTING: Infertility clinic. PATIENTS: Thirty-five women with normal intrauterine
      pregnancy. INTERVENTIONS: Serial measurement of the serum hCG level and the
      diameter of the gestational sac through transvaginal ultrasonography. MAIN
      RESULTS: The gestational sac could not be visualized when the hCG level was less
      than 1100 IU/L. The average growth rate of the sac was 0.9 mm/d. The threshold
      values for sac diameter, serum hCG level and gestational age below which the yolk
      sac was not visible were 3.7 mm, 1900 IU/L and 36 days respectively; the
      corresponding values above which the yolk sac was always visible were 6.7 mm,
      5800 IU/L and 40 days. The threshold values below which cardiac activity was not
      visible were 8.3 mm, 9200 IU/L and 41 days respectively, and the corresponding
      values above which cardiac activity was always visible were 14.0 mm, 24,000 IU/L
      and 46 days. The mean gestational ages and the 95% confidence and prediction
      intervals were tabulated so that measurement of the gestational sac diameter
      could be used to estimate gestational age early in normal pregnancy. CONCLUSIONS:
      Transvaginal ultrasonography enables detection of an intrauterine sac and
      reliable estimation of gestational age on the basis of sac dimensions before an
      embryo can be seen.

PMID- 1993292
TI  - Quality of abstracts of original research articles in CMAJ in 1989.
AB  - PURPOSE: To evaluate the quality of abstracts of original research articles.
      DESIGN: Blind, criterion-based survey. SAMPLE: Systematic sample of 33 abstracts
      of original research articles published in CMAJ in 1989. MEASUREMENT: The quality
      of abstracts was measured against a checklist of evaluation criteria, which were
      divided into eight categories. A score for each abstract was obtained by dividing
      the number of criteria present by the number applicable. The overall mean score
      was also determined. RESULTS: The overall mean score of abstract quality was 0.63
      (standard deviation 0.13) out of 1. Of the abstracts reporting study design 56%
      did not include specific technical descriptors. About 52% did not explicitly
      describe the study variables. In describing subject selection 79% failed to use
      specific technical terms. Of the abstracts reporting results 66% did not provide
      appropriate supporting data. Of those that gave conclusions 86% did not address
      study limitations and 93% made no recommendations for future study. CONCLUSION:
      Most of the abstracts provided some information pertaining to each evaluation
      criterion but did not provide detail sufficient to enhance the reader's
      understanding of the article. On the basis of the study sample the abstracts need
      improvement in description of research design, reporting of subject selection and
      results, and statements of limitations and recommendations. The small sample from
      one journal and the absence of comparison between the contents of the abstracts
      and the contents of the articles were limitations. Future studies should address
      these issues and compare the quality of traditional and structured abstracts.

PMID- 1993293
TI  - Severe falciparum malaria in nonendemic areas: an unrecognized medical emergency.

PMID- 1993294
TI  - Regression of atherosclerosis.

PMID- 1993295
TI  - Gulf deployment highlights need for stronger medical reserve, military says.
      Interview by Patrick Sullivan.

PMID- 1993296
TI  - Medicine and the microphone: using the media to teach our patients.

PMID- 1993297
TI  - Looming manpower shortage has Canada's obstetricians worried.

PMID- 1993298
TI  - Statistician and physicians at odds over Canada's AIDS statistics.

PMID- 1993299
TI  - New submissions adding to federal government's drug-approval backlog.

PMID- 1993300
TI  - Canada's Green Plan: "I had expected so much more".

PMID- 1993301
TI  - Rare chromosomal aberrations induced by vincristine. Partial endoreduplication
      and pseudoendoreduplication, segmentally endoreduplicated chromosomes, and
      segmental premature chromosome condensation.
AB  - Vincristine (VCR) is capable of inducing a cell containing both conventional
      chromosomes (monochromosomes) and diplochromosomes. A total of 124 such
      metaphases were examined by 5-bromodeoxyuridine (BrdU) incorporation and
      fluorescence plus Giemsa (FPG) technique to analyze cell cycle kinetics. The
      majority of cells (119 metaphases) showed differential BrdU incorporation between
      the two kinds of chromosomes, indicating that partial endoreduplication occurred
      in these cells. In addition, existence of partially endoreduplicated cells with
      premature chromosome condensation (PCC) in either mono- or diplochromosomes
      suggests that the timing of monochromosome-replication was very variable in
      individual cells. On the other hand, the remaining five metaphases showed that
      both mono- and diplochromosomes incorporated BrdU similarly, indicating that
      diplochromosomes are formed by pseudoendoreduplication. Two kinds of chromosomal
      aberrations probably caused by delay of DNA synthesis on chromosome segments,
      segmental endoreduplication, and segmental PCC were also reported. Segmental
      endoreduplication was defined as endoreduplication that occurred on some segments
      of chromosomes. Out of 119 partially endoreduplicated cells, 3 contained a
      chromosome consisting of both mono- and diplochromosomal segments, indicating
      that the former segments missed one round of DNA synthesis. Segmental PCC was
      defined as PCC restricted to only some segments of chromosomes. Two types of
      segmental PCC, segmental S-PCC and G2-PCC, were observed in VCR-induced ordinary
      polyploidy. Although both segmental endoreduplication and segmental PCC occurred
      with very low frequency, these phenomena suggest that DNA synthesis was disturbed
      in some part of the nucleus.

PMID- 1993302
TI  - Chromosomal characteristics of chronic and blastic phase of chronic myeloid
      leukemia. A study of 100 patients in India.
AB  - We report the cytogenetic findings of 100 patients with chronic myeloid leukemia
      (CML) [72 patients in chronic phase (CP) and 28 patients in blastic phase (BP)].
      Of the 95 Ph + patients, six had Ph variant translocations involving chromosomes
      1, 6, 7, 10, and 12. The percentage frequency of patients with chromosomal
      changes other than Ph was 7.3%. The additional aberrations (e.g., + Ph, + 8,
      i(17q), and + 19 were observed in 66.6% of BP patients. Of these anomalies, the
      frequency of + Ph and + 19 was higher in our patients than the incidence reported
      in literature. The association of + Ph and + 19 in patients with extramedullary T
      cell blast crisis is an unusual finding as compared with reports in the
      literature and could be explained by geographic heterogeneity. The extra
      chromosomal abnormalities were almost absent in lymphoid blast crisis patients
      with blast phenotype of common acute lymphoblastic leukemia (ALL) type.
      Discrepancies were noted in different tissues (bone marrow and lymph node) in
      patients with extramedullary blast crisis of both myeloid and lymphoid type.
      These findings indicate the cytogenetic correlation with clinical and
      morphological picture, which consequently implicates the diagnostic and
      prognostic significance of chromosomal aspects.

PMID- 1993303
TI  - Preferential involvement of 11q23-24 and 11p15 in breast cancer.
AB  - Thirty cases of breast cancer were cytogenetically studied by G-banding using
      direct tumor preparations. Among them 20 cases exhibited abnormalities of the
      long and/or short arm of chromosome 11. Thus, 11q was involved in 16 cases and
      11p in ten cases. There was consistent involvement of bands 11q23-24 (15 cases)
      and 11p15 (9 cases), where the cellular oncogenes ets and H-ras 1, respectively,
      are located. These findings suggest that involvement of bands 11q23-24 and 11p15
      may be specific in a group of breast cancers, leading to the activation of
      cellular oncogenes or loss of cancer suppressor genes.

PMID- 1993304
TI  - "Jumping" translocations involving band 3q13.3 in a case of acute monocytic
      leukemia.
AB  - We report a case of acute monocytic leukemia (FAB-5a) with a very aggressive
      clinical course and multiple chromosomal abnormalities. There were several
      sublines, each with trisomy 8 and a translocation involving 3q13.3 as a common
      breakpoint region. This region is an uncommon site of chromosomal breakage in
      malignancies and has not hitherto been reported as a breakpoint site in "jumping"
      translocations.

PMID- 1993305
TI  - Trisomy 8 as a nonrandom secondary change in myxoid liposarcoma.
AB  - We report the cytogenetic findings in 5 cases of myxoid liposarcoma following
      short-term culture. In all 5 tumors a t(12:16)(q13:p11), characteristic of the
      myxoid form of liposarcoma, was observed. Trisomy 8 was present in two tumors as
      the only additional change and in a third in addition to other abnormalities. In
      the other two tumors the t(12:16) was present as the sole change. Three other
      myxoid liposarcomas with trisomy 8 as an additional aberration have been
      reported, suggesting that it could represent a non-random secondary event in
      these tumors.

PMID- 1993307
TI  - Cytogenetic survey of 31 patients treated with bone marrow transplantation for
      acute nonlymphocytic and acute lymphoblastic leukemias.
AB  - The authors report on a sequential cytogenetic study carried out on 31 patients
      with acute leukemia (20 with acute lymphoblastic leukemia and 11 with acute non
      lymphocytic leukemia) who underwent bone marrow transplantation (BMT).
      Engraftment was documented in all patients with sex-mismatched donors and with
      donor constitutional aberrations. During the follow-up, ranging from 6 to 110
      months, clinical and hematologic relapse was observed in 11 patients (35.5%).
      Five of these cases showed a normal karyotype, 3 were of undefined relapse
      origin, 2 were aneuploid karyotypes, and one was donor (male) metaphases.
      Cytogenetic and immunologic data in the latter patient were suggestive of relapse
      in donor cells.

PMID- 1993306
TI  - A case of basophilic leukemia bearing simultaneous translocations t(8;21) and
      t(9;22).
AB  - We report a case of basophilic leukemia with simultaneous translocations of
      t(8;21) and t(9;22). The patient's clinical and hematologic findings were
      characteristic only of t(9;22) but not of t(8;21). This unusual cytogenetic
      phenomenon raises a challenge to the current concepts of primary chromosomal
      abnormalities in cancer.

PMID- 1993308
TI  - Acute myelomonocytic leukemia with bone marrow eosinophilia and
      inv(16)(p13q22),t(1;16)(q32;q22).
AB  - A two-year-old girl presenting with de novo acute myelomonocytic leukemia with
      eosinophilia (French-American-British [FAB] classification, M4Eo) and
      inv(16)(p13q22), t(1;16)(q32;q22) involving the same chromosome 16 is described.
      This is the second report of a variant translocation of an inverted chromosome 16
      with chromosome 1 at 1q32. However, the segment 1q32----1qter has been exchanged
      for 16q22----qter and not 16p13----pter, as reported in the previous case. The
      additional break at 1q32 and the juxtaposition of 1q32----qter onto chromosome 16
      could be relevant to the pathogenesis of the disease.

PMID- 1993309
TI  - New chromosomal rearrangement, t(12;22)(p13;q12), in acute nonlymphocytic
      leukemia.
AB  - The karyotype 47,XX, + 8,t(12;22)(p13;q12) was found at diagnosis in two patients
      with acute nonlymphocytic leukemia (ANLL). The bone marrow morphology of both
      patients corresponded to the M4 subtype of the French-American-British (FAB)
      classification. The translocation t(12;22) has not previously been reported as
      the sole structural aberration in ANLL.

PMID- 1993311
TI  - Centromeres without kinetochore proteins. Another mechanism for origin of
      aneuploidy in neoplasia.
AB  - Centromeres of all chromosomes in normal cells exhibit kinetochore proteins
      detectable by antikinetochore antibodies. The present communication reports that
      some chromosomes in a transformed cell line of rat cerebral origin fail to
      deposit kinetochore proteins at their centromeres. These chromosomes may not
      undergo normal anaphase segregation and may be either lost or enter one or the
      other daughter cell. The observation that some chromosomes may be without
      detectable kinetochore proteins suggests a noval mechanism for origin of
      aneuploidy in transformed and neoplastic cells.

PMID- 1993310
TI  - Studies of BCR rearrangements in Philadelphia-positive acute leukemia.
AB  - Five patients with Philadelphia-positive acute leukemia were cytogenetically and
      molecularly investigated in order to determine the localization of the
      breakpoints on chromosome 22. Rearrangements of the bcr segment were detected in
      one case with acute mixed leukemia in a child. Rearrangements in the BCR gene
      first intron, the so-called bcr2 and bcr3 regions, were detected in two other
      cases, one with an acute lymphoblastic leukemia (ALL) and one with mixed acute
      leukemia. No molecular rearrangement could be detected in the last two cases, an
      ALL and a T-cell acute lymphoblastic leukemia with a t(2;22) translocation.

PMID- 1993312
TI  - Trisomy 5 in Ph+ chronic myeloid leukemia in association with megakaryocytosis.
AB  - A patient with a megakaryocytosis associated with a Philadelphia chromosome
      positive chronic myeloid leukemia (CML) was found to have a trisomy of chromosome
      five. To our knowledge, this is the first case of trisomy 5 associated with a Ph
      + CML, particularly one with a megakaryocytosis. The trisomy 5 may be associated
      with the resistance to cytostatic drugs found in this patient.

PMID- 1993313
TI  - Atypical chronic myelomonocytic leukemia with eosinophilia and translocation
      (5;12). A new association.

PMID- 1993314
TI  - Involvement of 6p in an endometrial polyp.

PMID- 1993315
TI  - Therapeutic drug monitoring revisited.

PMID- 1993316
TI  - Immunometric assays of parathyrin in the diagnosis of hypercalcemic individuals.

PMID- 1993317
TI  - Approaches to minimizing interference by cross-reacting molecules in
      immunoassays.
AB  - Here we review techniques useful in eliminating or reducing interferences caused
      by molecules that cross-react in immunoassays. The biochemical rationale for
      using these techniques is discussed. Examples are taken from recent studies aimed
      at reducing interferences caused by endogenous molecules such as digoxin-like
      immunoreactive factors or steroid hormones. In this context the role of protein
      binding of cross-reacting molecules is also considered. Immunoassay ligand
      selectivity can be inherently limited by the heterogeneity of the antigenic
      response or by the structural similarity of epitopes on multiple ligands. Certain
      empirical approaches have proved useful in maximizing the analytical specificity
      of immunoassays. These approaches include isolating the relevant ligands before
      immunoassay, adjusting the kinetic or equilibrium conditions used during the
      assays, and developing more specific antisera. The physicochemical properties of
      the cross-reacting molecule best dictate which technique(s) to use. The
      approaches discussed here are general and apply to minimizing interference caused
      by a wide variety of both endogenous and exogenous cross-reacting molecules.

PMID- 1993318
TI  - Analytical goals for determinations of theophylline concentration in serum.
AB  - Statistical principles for analytical goal-setting were applied to two medical
      applications of drug-monitoring data: (a) individualizing dosage requirements by
      reference to a population-based therapeutic range or to a patient-specific
      decision value determined by Bayesian decision analysis, and (b) prospective
      dosing by using pharmaco-kinetic principles. For application a, the analytical
      goal for total allowable analytical error (TE) was defined as the amount of error
      that does not decrease by more than 5% either the sensitivity (probability) for
      detecting dosage regimens that may require modification or the specificity for
      detecting appropriately dosed patients. The limiting factor in achievable
      sensitivity and specificity was the intra-individual variation of peak steady
      state concentration (Css), with the TE determined to be a CV of 4%. For
      application b, error-propagation rules were applied to a proposed prospective
      dosing scheme (J Pharmacokinet Biopharm 1978;6:135-51). The TE was determined to
      depend on the rate of theophylline clearance. For clearance rates less than or
      equal to 0.6 mL/(kg.min), the TE (CV) must not exceed 3% if the predicted
      infusion rate is to produce, with 95% confidence, a concentration within the
      therapeutic range.

PMID- 1993319
TI  - Immunochemiluminometric and immunoradiometric determinations of intact and total
      immunoreactive parathyrin: performance in the differential diagnosis of
      hypercalcemia and hypoparathyroidism.
AB  - Parathyrin (parathyroid hormone; PTH) was measured with three immunoassays: a two
      site immunochemiluminometric (ICMA) and a two-site immunoradiometric (IRMA)
      method for intact PTH, and a sensitive radioimmunoassay for mid-region or "total"
      PTH, measuring both intact hormone and inactive fragments. Single specimens from
      normal subjects and from individuals with primary hyperparathyroidism,
      hypercalcemia associated with malignancy, and hypoparathyroidism were analyzed
      with all three methods. All individuals with primary hyperparathyroidism showed
      absolutely above-normal concentrations with the mid-region RIA, 28 of 29 did with
      the ICMA, and 21 of 29 did with the IRMA. PTH concentrations in primary
      hyperparathyroidism were most increased relative to normal subjects with the mid
      region assay (10.4 times), less so with the intact assays (ICMA 5.5 times; IRMA
      5.3 times). Concentrations of intact PTH were suppressed below normal in nearly
      all patients with hypercalcemia associated with malignancy, as measured with the
      ICMA (26 of 30) and the IRMA (28 of 30) assays. In marked contrast, results for
      mid-region PTH were normal or slightly above normal, consistent with studies
      suggesting that the parathyroids secrete both intact hormone and inactive
      fragments, the former being more sensitive to suppression by hypercalcemia. In
      hypoparathyroidism PTH concentrations were detectable but below normal in all
      patients by the intact assays and in all but one patient by the mid-region assay.
      These low concentrations are probably due to a nonspecific serum effect that
      could be resolved with selection of a more appropriate standard matrix. Although
      all three assays are useful in the differential diagnosis of hypercalcemia, two
      site intact assays are more convenient and more specific in patients with
      compromised renal function.

PMID- 1993320
TI  - New enzyme-linked immunosorbent assay for glycocalicin in plasma.
AB  - A new sandwich-type enzyme-linked immunosorbent assay for quantifying
      glycocalicin, a proteolytic fragment of platelet membrane glycoprotein Ib, is
      described. The assay is based on the use of two monoclonal antibodies raised
      against glycoprotein Ib and involves the avidin-biotin technique. The detection
      limit is 7 micrograms/L and the range of glycocalicin determined in plasma is
      0.01 to 1 mg/L. Assay time is 2 h. The intra-assay CV ranged from 3.6% to 5.2%,
      the interassay CV from 5.4% to 8.0%. Analytical recovery of purified glycocalicin
      added to a plasma pool averaged 96%. In 36 healthy subjects, the mean
      glycocalicin concentration in plasma was 0.36 (SD 0.07) mg/L (2.7 nmol/L). We
      conclude that this assay is suitable for measuring glycocalicin in plasma and is
      also more sensitive and precise than the previously published immunoassays based
      on competitive binding assay.

PMID- 1993321
TI  - Complexes of creatine kinase and immunoglobulins in serum identified by a
      nonimmune binding method.
AB  - We have developed a method for identifying IgG-complexed creatine kinase (CK; EC
      2.7.3.2) (IgG-CK) and IgA-complexed CK (IgA-CK) in serum. We used immobilized
      Protein G to bind IgG-CK and immobilized jacalin to bind IgA-CK, leaving
      noncomplexed CK in solution. The noncomplexed CK and total CK were measured
      kinetically. The results are reported as CK bound to immobilized Protein G and CK
      bound to immobilized jacalin. We validated the method by using sera determined
      immunochemically to contain IgG-CK, IgA-CK, mitochondrial CK (CKmt), and free CK
      BB. We demonstrated concomitant binding of CK and approximately 99% of IgG, and
      of CK and approximately 87% of IgA. For CK bound to immobilized Protein G and to
      immobilized jacalin, intra- and interassay precisions ranged from 2.5% to 9.6%,
      and detection limits were less than 9 318 U/L in 40 sera containing IgG-CK, and
      CK bound to immobilized jacalin ranged from 10 to 59 U/L in eight sera containing
      IgA-CK. These ranges represent the activities of immunoglobulin-bound CK in the
      sera. In 13 sera containing CKmt and in eight sera containing free CK-BB, the
      binding of CK was less than 9 U/L. Evidently, this method is useful for
      identifying IgG-CK and IgA-CK in serum.

PMID- 1993322
TI  - Interlaboratory comparison of the measurement of albumin in urine.
AB  - Because of increased interest in the assay of albumin in urine and the
      sensitivity required to quantify concentrations associated with (a) increased
      risk of developing end-stage renal disease and cardiovascular disease among
      people with diabetes and (b) renal damage caused by exposure to nephrotoxic
      substances, we conducted a pilot study of the variation of these measurements
      within and among five laboratories that use various immunoassays. These assays
      included two different enzyme immunoassays, two different immunoturbidimetric
      assays, a fluorescent immunoassay, and a zone immunoelectrophoresis assay. The
      results indicate considerable variation both within and among laboratories for
      measurements at or near the normal range. Variability is equally attributable to
      the precision of individual immunoassays and to the variation of the mean values
      obtained by each laboratory. Individual laboratory CVs ranged from 5.8% to 18.2%
      for mid- and high-concentration samples treated with preservative and from 8.4%
      to 23.6% for mid- and high-concentration samples containing no preservative. The
      relative bias of individual laboratory means ranged from -56.4% to 20.5% for the
      two preserved materials and from -32.6% to 0.8% for the two materials containing
      no preservative. To reduce the chance of misdiagnosing the risk associated with
      above-normal albumin concentrations in urine, we need to address the problems
      contributing to imprecision and inaccuracy, particularly laboratory-to-laboratory
      variability.

PMID- 1993323
TI  - Catecholamine sulfates as internal standards in HPLC determinations of
      sulfoconjugated catecholamines in plasma and urine.
AB  - A method is described to measure catecholamine sulfates from human plasma and
      urine by isocratic reversed-phase high-performance liquid chromatography with
      electrochemical detection. For this measurement we use catecholamine 3-sulfate
      isomers as internal standards and determine the sulfoconjugates only after
      eliminating the catecholamines. Catecholamines that have previously been used as
      internal standards are shown to cause a significant overestimation (P less than
      0.05) of the catecholamine sulfates--by 10% to 25% and 20% to 42% in human plasma
      and urine, respectively. The detection limits (signal-to-noise ratio greater than
      3) in plasma and urine samples were about 80 pmol/L for each analyte. The intra
      assay and interassay CVs were less than 4.0% and 10.6% in human plasma and less
      than 6.6% and 12.8% in human urine, respectively. The calibration curves for all
      catecholamine sulfates in human plasma and urine were linear (r greater than
      0.96; P less than 0.001) over the respective concentration ranges of 0.1-100
      nmol/L and 5-1000 nmol/L.

PMID- 1993324
TI  - Plasma protein-bound sialic acid in patients with colorectal polyps of known
      histology.
AB  - Protein-bound sialic acid (PBSA) was measured in serial plasma specimens from 62
      healthy subjects, 48 patients with colorectal polyps, and 30 patients with
      colorectal adenocarcinomas. The mean plasma PBSA concentration in healthy smokers
      was significantly greater than that in healthy nonsmokers and healthy ex-smokers
      (P less than 0.0001). Villoglandular polyps were associated with higher plasma
      PBSA values than were the most benign hyperplastic polyps (P less than 0.025).
      Patients with the most neoplastic villoglandular and villous polyps had
      significantly greater (P less than 0.010-0.050) plasma PBSA values than healthy
      subjects. Polypectomy decreased the mean PBSA value significantly to the mean
      value for healthy subjects only for patients with villoglandular (P less than
      0.010) or villous (P less than 0.050) polyps. Colorectal cancer patients had mean
      plasma PBSA concentrations significantly greater than those for the healthy
      subjects (P much less than 0.001) and the polyp patients (P much less than
      0.001). Surgery significantly reduced (P less than 0.025) the mean PBSA value for
      the cancer patients to the mean PBSA value observed for the healthy subjects.

PMID- 1993325
TI  - Methadone concentrations in plasma and their relationship to drug dosage.
AB  - We have developed a sensitive HPLC method for measuring methadone in plasma and
      have used it to establish that there is a linear relationship between plasma
      concentration and methadone dose over the range of 3-100 mg of methadone per day
      in a group of 31 addicts. We found a good correlation between dose and plasma
      concentration (r = 0.89), with the plasma methadone concentration increasing by
      0.263 mg/L for every milligram of methadone consumed per kilogram of body weight.
      Five patients had unexpected high or low concentrations; this finding is
      discussed.

PMID- 1993326
TI  - Multielement analysis of biological samples by inductively coupled plasma-mass
      spectrometry. II. Rapid survey method for profiling trace elements in body
      fluids.
AB  - A rapid survey of the elements in biological materials, covering most of the
      elements in the periodic table, is possible by using available software for semi
      quantitative analysis (SEMI-QUANT) by inductively coupled plasma-mass
      spectrometry. The procedure takes 5 min after sample preparation and gives
      results with a precision (CV) of approximately 20%. At a 10-fold dilution, 13
      elements can be consistently and reliably detected in serum and 15 elements in
      whole-blood samples. At present the most important limitation of this method is
      mass overlap by polyatomic species for some elements of interest (e.g., Cr, Mn,
      and V). However, for the set of elements that can be reliably determined at
      endogenous concentrations, including Li, B, Mg, Fe, Cu, Zn, Rb, and Sr, the rapid
      scanning capability may be useful. Although matrix effects limit the direct
      interpretation of the semi-quantitative output, reasonable estimates of
      concentration are attainable by using matrix-matched standards or by adding a
      multielement standard to an aliquot from one sample in the set. We also present
      an example of determination of 25 elements in saliva from a patient with
      extensive dental work: Components of many of his dental alloys were readily
      identified. The method may also prove useful for screening multiple toxic
      exposures to heavier elements, such as Pb, Tl, Cd, and Hg.

PMID- 1993327
TI  - Observational study of erythrocyte protoporphyrin screening test for detecting
      low lead exposure in children: impact of lowering the blood lead action
      threshold.
AB  - We examined a retrospective sample of 1800 children on whom both erythrocyte
      protoporphyrin (EP) and blood lead (BPb) measurements were taken. The primary
      objective was to ascertain whether EP is a cost-effective screening test for low
      but increased BPb concentrations and to establish the optimal thresholds. The
      data did not provide evidence of an EP threshold at low BPb concentrations;
      however, the data did show a significant age effect. A subset of 500 children for
      whom both EP and hematocrit data were available showed no correlation between
      those variables. Age-specific operating characteristic curves, total error, and
      cost analyses are presented. The latter sets bounds on the relative cost of EP
      testing, above which only BPb determination should be performed. The implications
      of these findings are discussed in light of impending changes in U.S. federal
      guidelines for preventing lead poisoning in young children.

PMID- 1993328
TI  - Practical method for optimizing radioimmunoassay detection and precision limits.
AB  - A model of the competitive radioimmunoassay standard curve, based on the Law of
      Mass Action, has been developed and used in conjunction with experimental and
      counting errors to predict the assay detection limit and precision profiles. We
      verified the model with hapten radioimmunoassays performed in our laboratory. The
      resulting computer program can be used to determine the optimum antiserum
      concentration--depending on its affinity--and labeled-antigen concentration-
      according to its specific activity and nonspecific binding. The graphical
      representation of this model provides radioimmunologists with a practical tool
      for assay optimization.

PMID- 1993329
TI  - Standardization, specificity, and diagnostic sensitivity of four immunoassays for
      carcinoembryonic antigen.
AB  - Four "sandwich"-type immunoassays for carcinoembryonic antigen (CEA) based on
      monoclonal antibodies (Abbott CEA-RIA Monoclonal, Pharmacia/Wallac Delfia CEA
      kit, Roche CEA EIA Duomab 60, and our in-house immunoradiometric assay) were
      compared for 357 samples from colorectal cancer patients and samples from 48
      patients with chronic liver disease or with acute, irrelevant diseases. Relative
      to a common 5 micrograms/L reference limit, all four assays agreed regarding
      classification in 92% to 94% of the samples in the colorectal cancer samples,
      with the Abbott and Roche assays giving slightly more "normal" values. Cross
      testing of CEA standards and the 1st International Reference Preparation 73/601
      showed that calibration differences could not be eliminated by the use of a
      common standard. It has been earlier demonstrated that the monoclonal antibodies
      in the Roche assay have an epitope group specificity slightly different from
      those of the other three assays. This can explain why the correlations involving
      the Roche assay were weaker (r = 0.84-0.87) than those obtained with the other
      assays (r = 0.94-0.97). I conclude that agreement between the assays studied is
      as good as can be expected when different antibodies are used; nevertheless,
      consistent discrepancies between assays in several patients still necessitate the
      use of the same assay during follow-up.

PMID- 1993330
TI  - Use of a synthetic soluble bilirubin derivative to assess interference in
      creatinine measurements.
AB  - In assessing interference from bilirubin, the use of a synthetic soluble
      derivative (ditaurobilirubin, DTB) is recommended as a surrogate for the natural
      conjugates (Bc). We compared the interference effect of unconjugated bilirubin
      (Bu), Bc, and DTB, using six mechanized methods for serum creatinine measurement.
      No significant interference was noted in methods that include removal of proteins
      or in an enzymatic method involving NADH oxidation. Heavy (negative) interference
      was observed in an alkaline picrate method, and in direct enzymatic methods based
      on hydrogen peroxide measurement: interference was always more pronounced in the
      presence of the two soluble derivatives (Bc and DTB), whose interference was of
      the same magnitude. These results point out the utility of testing for bilirubin
      interference by using soluble derivatives, in addition to Bu, and suggest the
      feasibility of using DTB as a surrogate for Bc for this purpose.

PMID- 1993331
TI  - Precipitation with polyethylene glycol and density-gradient ultracentrifugation
      compared for determining high-density lipoprotein subclasses HDL2 and HDL3.
AB  - The purpose of this study was to compare quantification of cholesterol in high
      density lipoprotein subfractions HDL2 and HDL3 by precipitation with polyethylene
      glycol (PEG) with that by density-gradient ultracentrifugation. Fresh serum
      samples from 32 fasting, obese children were analyzed with precipitation reagent
      "Quantolip" (Immuno AG), and then fractionated with a Beckman TL 100
      ultracentrifuge with a swinging-bucket rotor. After centrifugation we carefully
      removed the supernate with a syringe and measured the cholesterol from each
      fraction enzymatically with CHOD-PAP reagent (Boehringer Mannheim). The low
      density lipoprotein (LDL-), HDL2-, and HDL3-cholesterol values measured by
      ultracentrifugation did not differ significantly from those obtained by
      precipitation; the correlation coefficients (r) between the two methods were 0.96
      for LDL, 0.75 for HDL2, and 0.96 for HDL3. The relatively simple PEG
      precipitation method used in this study measures total HDL and its major
      subclasses HDL2 and HDL3 with accuracy and precision comparable with those of the
      well-established ultracentrifugation method.

PMID- 1993332
TI  - Analysis of apolipoprotein E genotypes by the Amplification Refractory Mutation
      System.
AB  - The Amplification Refractory Mutation System (ARMS) has been successfully applied
      to the detection of apolipoprotein (apo) E genotypes in human DNA extracted from
      peripheral blood. By using four allele-specific oligonucleotide primers and one
      common primer, one can identify the three common alleles of the apo E genetic
      polymorphism, epsilon 2, epsilon 3, and epsilon 4. The system amplifies two
      sequences of the apo E gene, one of 181 bp and the other 319 bp. These sequences
      are amplified when DNA containing a particular allele is incubated with its
      allele-specific oligonucleotide primer and a common primer. The method is simple,
      reliable, and nonisotopic and obviates the need for digestion with restriction
      endonucleases or for hybridization with allele-specific oligonucleotide probes.
      Genotyping DNA by this method overcomes the problem of post-translational
      modification of the apo E phenotype encountered with isoelectric focusing of the
      mature plasma apo E protein.

PMID- 1993333
TI  - Electrochemical enzyme immunoassay for phenytoin by flow-injection analysis
      incorporating a redox coupling agent.
AB  - Using phenytoin as a model analyte, we demonstrate an electrochemical enzyme
      immunoassay based on flow-injection analysis and incorporating 2,6
      dichloroindophenol (DCIP) as a redox coupling agent. DCIP reacts with NADH to
      form NAD+ and DCIPH2, the reduced form of the coupling agent. The production of
      DCIPH2 is monitored at +250 mV vs Ag/AgCl. This low applied potential improves
      selectivity in the biological matrix, differentiating against components that are
      oxidizable at the more-positive potentials required for direct electrochemical
      detection of NADH. The kinetics-based assay also eliminates other common
      interferences, mainly from ascorbic acid and glutathione. This system does not
      require precolumns or analytical columns for isolation of the NADH response. Good
      agreement with a routine clinical laboratory procedure for phenytoin is obtained
      for clinical samples (r = 0.95), illustrating the feasibility of such an
      approach.

PMID- 1993334
TI  - Simplified format for DNA probe-based tests.
AB  - The approach I describe to using DNA probes in diagnostic tests is simpler than
      most existing formats. DNA in a sample is labeled by chemical reaction with
      bisulfite and methylamine to generate a sulfonated derivative. The DNA need not
      be purified to do this. The labeled sample is then incubated with an unlabeled,
      purified probe DNA, which is immobilized to a solid support. The amount of label
      remaining on the solid support after washing is detected by a monoclonal antibody
      that recognizes modified cytosines. The intensity of the signal depends on the
      amount of target DNA in the sample. Detection limits depend on the amount of
      immobilized DNA and on the degree of physical entrapment of the labeled DNA in
      sample material, but can be as low as 5 pg. This format is well suited to
      automation for use with existing robotic enzyme immunoassay procedures.

PMID- 1993335
TI  - Competitive particle concentration fluorescence immunoassay for measuring 5,10
      dideaza-5,6,7,8-tetrahydrofolic acid (lometrexol) in serum.
AB  - A competitive particle concentration fluorescence immunoassay (PCFIA) is
      described for measuring 5,10-dideaza-5,6,7,8-tetrahydrofolic acid (lometrexol;
      Lilly) in human serum. b-Phycoerythrin-labeled lometrexol competes with free
      lometrexol for binding to a limiting concentration of lometrexol-specific
      antibodies immobilized by a second antibody to submicrometer-diameter polystyrene
      particles in specially designed 96-well plates. Reaction particles are washed and
      concentrated onto filter membranes in the wells of the plates and the
      fluorescence is measured at 575 nm. The method, including sample preparation and
      data reduction, is automated and can be completed in less than 2 h. The assay has
      a standard curve maximum measurable concentration of 1000 micrograms/L and a
      minimum detectable concentration of 0.1 microgram/L. Analytical recovery of
      lometrexol in serum is quantitative at concentrations greater than 1
      micrograms/L. Intra- and interassay coefficients of variation at 50 micrograms/L
      in serum are 7.1% (n = 9) and 7.5% (n = 33), respectively. The cross-reactivity
      of naturally occurring folates, folic acid analogs, and the anti-cancer agent
      methotrexate is minimal. We report the use of the PCFIA during Phase I clinical
      studies designed to evaluate the pharmacokinetics of lomextrexol after
      intravenous administration to cancer patients.

PMID- 1993336
TI  - Iron, transferrin, and ferritin in cerebrospinal fluid of children.
AB  - We measured iron, ferritin, and transferrin in cerebrospinal fluid (CSF) of
      pediatric patients. Because the concentrations of iron and iron-binding proteins
      in CSF in these samples were lower than those ordinarily measured in older
      subjects, we had to modify the lower limit of detection of the methods used. The
      concentrations of these three analytes in patients with viral meningitis were
      higher than those in healthy infants and children.

PMID- 1993337
TI  - Mathematical model for comparing proficiency testing results across analytical
      methods.
AB  - Proficiency testing (PT) programs may fail to establish a range of acceptable
      performance in a challenge when an insufficient number of participants use a
      particular method. In this study I analyzed a mathematical approach to establish
      acceptable performance in alanine aminotransferase (ALT; EC 2.6.1.2) PT
      challenges. This approach was derived from the mathematical model used in
      establishing a nationwide ALT standardization system for blood-collection
      facilities in 1988. A ratio of results was derived between each method in the PT
      program and an arbitrarily chosen "standard" method. The intent of this approach
      was to transform a target value for a challenge as determined in the "standard"
      method to units applicable to methods utilized less often. However, the high
      degree of variability over time in the ratios for some methods precluded general
      application of this approach. Therefore, although this simple mathematical method
      was successful in implementing an ALT standardization system across different
      methods, a derivation of this approach did not afford comparison of results in PT
      challenges.

PMID- 1993338
TI  - Isotopic and nonisotopic assays for measuring somatotropin compared: re
      evaluation of cutoff value in provocative tests.
AB  - Measurement of human growth hormone (hGH; somatotropin) concentrations in serum
      after provocative tests is crucial for diagnosing deficiencies in production of
      this hormone. Serum hGH can be measured by various immunoassays, isotopic and
      nonisotopic, with monoclonal or polyclonal antibodies: a cutoff value of 10
      micrograms/L after provocative testing is usually used to distinguish normal from
      hGH-deficient children. Previous studies demonstrated discrepancies in hGH
      measurement by different radioisotopic immunoassays. Here we evaluated the
      responses of six different commercial assays, radioisotopic and nonisotopic, with
      monoclonal or polyclonal antibodies in a series of 16 provocative tests
      (stimulation with clonidine) in short children. A wide range of discrepant values
      was obtained with the different kits. A cutoff of 10 micrograms/L produced
      discordance of diagnosis among assays for two children, whereas complete
      agreement was reached for a cutoff value of 7 micrograms/L. Parallelism tests
      performed with hGH international standard, pure recombinant hGH, and a serum with
      high hGH content suggest that heterogeneity of the antibodies used by the
      manufacturers, even among monoclonal antibodies, is the main source of discordant
      results. Cutoff values and reference values must be established separately for
      each method proposed for routine use.

PMID- 1993339
TI  - Partial purification of endogenous digitalis-like compound(s) in cord blood.
AB  - Increasing evidence indicates the presence of endogenous digitalis-like
      compound(s) in human body fluids. In this preliminary report, we describe a study
      of the partial purification by HPLC of these compounds in the plasma of neonates
      (who have particularly high concentrations of this substance) and adults. Plasma
      samples from neonates (cord blood) and adults, lyophilized and extracted with
      methanol, were applied on a 300 x 3.9 mm C18 Nova Pak column and eluted with a
      mobile phase of acetonitrile/methanol/water (17/17/66 or 14/14/72 by vol) and,
      after 30 min, with 100% methanol. We assayed eluted fractions for inhibitory
      activity of 86Rb uptake and for digoxin-like immunoreactivity. The elution
      profile revealed a first peak of inhibitory activity of 86Rb uptake at the
      beginning of the chromatography; another peak was eluted with the 100% methanol.
      The two peaks also cross-reacted with antidigoxin antibodies. Because the second
      peak could possibly reflect the nonspecific interference of various lipophilic
      compounds, we focused our attention on the first peak. For these fractions dose
      response curves for 86Rb uptake and for displacement of digoxin were parallel,
      respectively, to those of ouabain and digoxin, suggesting similarities of digoxin
      like immunoreactive substance to cardiac glycosides. Similar chromatographic
      profiles were also obtained for plasma from adults, suggesting that the
      endogenous glycoside-like compound(s) in the neonate may be the same as those in
      the adult.

PMID- 1993340
TI  - Osteocalcin concentrations in plasma prepared with different anticoagulants.
AB  - We investigated the effects on plasma osteocalcin concentrations of different
      anticoagulants used to collect the blood samples. Plasma osteocalcin
      concentrations measured by enzyme immunoassay and radioimmunoassay are influenced
      by the nature of the anticoagulants used. The most significant difference between
      concentrations found in plasma and serum was seen with oxalate/fluoride
      anticoagulant, which reduced osteocalcin concentrations to 37.3% of serum values.
      This is probably related to increased hemolysis with this anticoagulant compared
      with osteocalcin concentrations in plasma prepared with other anticoagulants.
      Samples prepared with sodium citrate (0.105 mol/L) or lithium heparin gave values
      92.4% and 83.6% of those obtained with matched serum samples. Osteocalcin
      concentrations were relatively stable in plasma and serum at -20 degrees C for
      two freeze/thaw cycles. In blood from 100 patients there was a good correlation
      between osteocalcin concentrations in serum and plasma (lithium heparin) (r2 =
      0.831); the slope and intercept (+/- SE) were 0.924 +/- 0.04 and 4.92 +/- 1.25
      micrograms/L, respectively. However, in 10 patients, serum osteocalcin
      concentrations were two- to threefold higher than those in matched plasma
      samples.

PMID- 1993341
TI  - Simple, optimized liquid-chromatographic method for measuring total
      hydroxyproline in urine evaluated.
AB  - We have optimized a method for measuring total hydroxyproline (HYP) in urine by
      HPLC after release from urinary peptides by solid-phase hydrolysis on Dowex 50W x
      8 ion-exchange resin. The HYP was derivatized with 4-chlor-7-nitrobenzo-2-oxa-1,3
      diazole, and excess reagent was removed with the use of a 100-mg C18 Bond-Elut
      cartridge. The HYP derivative was separated isocratically at 30 degrees C on a
      250 x 4.6 mm reversed-phase column containing 5-microns particles of Spherisorb
      S5 ODS-2, with S-carboxymethylcysteine as internal standard. Total assay time was
      14 min. The standard curve for the method was linear from the detection limit for
      HYP, 3.6 mumol/L, to 10 mmol/L. The between-batch CV was less than 5.1% and the
      mean analytical recovery of HYP was 95% +/- 1.4%. Comparison with a commercially
      available colorimetric method showed good correlation: y = 1.158x + 19.76 mumol/L
      (Syx = 74, n = 120), but HPLC results were 15% higher, probably from incomplete
      hydrolysis with the colorimetric method. This method offers a considerable
      improvement in assay time, specificity, sensitivity, precision, and cost compared
      with the colorimetric method.

PMID- 1993342
TI  - Clinical utility of cyclosporine concentrations determined in recipients of small
      bowel transplant by HPLC and fluorescence polarization immunoassay.

PMID- 1993343
TI  - Automated immunoassay for prolactin with the Abbott IMx analyzer.

PMID- 1993344
TI  - Consistency of the algorithm for pO2 correction in blood-gas analysis.

PMID- 1993345
TI  - Effect of hyperglycemia on plasma sodium and potassium concentration revisited.

PMID- 1993346
TI  - High-performance liquid chromatography of rapamycin.

PMID- 1993348
TI  - Robotics in the medical laboratory.

PMID- 1993347
TI  - Heterozygous hypobetalipoproteinemia with fasting chylomicronemia.
AB  - We describe a disorder in which low-density lipoprotein (LDL)-cholesterol and
      apolipoprotein B are in low concentration (0.47 mmol/L and 0.28 g/L,
      respectively) and chylomicrons are still present in plasma after an 18-h fast.
      The d less than 1.006 fraction was isolated by flotation ultracentrifugation and
      the apolipoproteins were analyzed by electrophoresis, immunoblotting with anti
      apolipoprotein B-100 antiserum, and isoelectric focusing. In the d less than
      1.006 fraction of the fasting serum, we found an apolipoprotein B form with the
      same apparent molecular mass as apolipoprotein B-48 and similar in amount to
      apolipoprotein B-100 (respective percentages, 46% and 54%). The monosialylated
      form of the apolipoprotein C-III was severely decreased. After an oral fat load,
      the repartition of the two species of apolipoprotein B did not change greatly
      (respective percentages, 60% and 40%), and the concentration of serum
      triglyceride increased only from 1.20 to 1.65 mmol/L.

PMID- 1993349
TI  - Urine and serum pregnancy tests compared.

PMID- 1993350
TI  - Bibliometrics and clinical chemistry.

PMID- 1993351
TI  - Identification of intestinal, intestinal variant, and high-Mr alkaline
      phosphatase with the resolve-ALP isoelectric focusing system.

PMID- 1993352
TI  - Serum creatine kinase 2 (CK-MB) in myocardial infarction: measure activity,
      percentage of total CK, or both?

PMID- 1993353
TI  - Direct analysis of capillary blood glucose with Kodak Ektachem analyzers.

PMID- 1993355
TI  - Hepatitis B surface antigen induces an early-type hypersensitivity.
AB  - In addition to the delayed-type hypersensitivity (DTH), a unique type of
      hypersensitivity could be induced at a late stage of the immune responses after
      hepatitis B surface antigen (HBsAg) immunization. This antigen-specific ear
      swelling that develops within 1 h after antigen challenge has been referred to as
      the early-type hypersensitivity (ETH) in contrast to the 24-h DTH. Although
      expression of ETH was earlier than DTH, the induction of the former needed 3 days
      longer than that of the latter. In ETH, the plasma protein leaked into the tissue
      and the vasopermeability increased within 15 min, causing the oedema of ETH. The
      observation that cyproheptadine, not dexamethasone, inhibited ETH suggests that
      it is mediated through the release of histamine and/or serotonin. Furthermore,
      ETH could be transferred by immune sera. Heat treatment (56 C for 4 h) did not
      destroy the transfer, suggesting that it was not mediated by IgE. The human anti
      HBs sera from either hepatitis B virus infection or HBsAg vaccinee also contained
      the activity to transfer the ETH in mice.

PMID- 1993354
TI  - Effect of a recombinant HIV gp160 vaccine on monokine production.
AB  - An investigation was undertaken to determine whether a recombinant gp160 envelope
      protein, which is currently being evaluated as a vaccine for AIDS, induces or
      modulates the production of tumour necrosis factor-alpha (TNF-alpha) or
      interleukin-1 beta (IL-1 beta). Incubation of monocytes from healthy, HIV
      seronegative persons with 0.0001-1.0 micrograms of the recombinant vaccine did
      not result in the secretion of TNF-alpha or IL-1 beta, nor did the recombinant
      product augment or suppress monokine production by lipopolysaccharide (LPS)
      stimulated monocytes. The vaccine was also without a stimulatory or modulatory
      effect upon TNF-alpha or IL-1 beta secretion by monocytes from a patient with the
      AIDS-related complex (ARC) and from the monocytic THP-1 cell line. The lack of
      effect of gp160 on monokine production has important implications for its
      efficacy as a vaccine for AIDS.

PMID- 1993356
TI  - Antibodies to pneumococcal polysaccharides in pneumonia and response to
      pneumococcal vaccination in young children in Papua New Guinea.
AB  - Antibodies against pneumococcal polysaccharides were measured by ELISA in Papua
      New Guinean children with pneumonia aged 0-14 months, in age-matched healthy
      Papua New Guinean controls and in healthy expatriate children living in Papua New
      Guinea. At 0-5 months of age, the IgG antibody titres against six of the eight
      polysaccharides measured were significantly lower in pneumonia patients than in
      both control groups. Antibody titres in 6-14-month-old Papua New Guinean controls
      were significantly lower than in control Papua New Guineans aged 0-5 months for
      five of the eight polysaccharides tested. In the 6-14-months age group the
      antibody titre was significantly lower in pneumonia patients than in controls for
      only one polysaccharide. For seven of the eight serotypes tested, antibody levels
      in expatriate controls did not decline with age. Antibody responses of Papua New
      Guinean children aged 6-18 months to a 23-valent pneumococcal vaccine were
      serotype dependent. Fold increases in response to the vaccine were greatest for
      the IgA isotype. IgG antibody responses were greater than three fold to four of
      the eight serotypes tested.

PMID- 1993357
TI  - Host and bacterial factors control the Mycobacterium avium-induced chronic
      peritoneal granulocytosis in mice.
AB  - Persistent peritoneal granulocytosis and elevated macrophage counts have been
      found in nine mouse strains from 8 to 90 days after infection with Mycobacterium
      avium. Peritoneal granulocytosis was higher in M. avium-resistant BALB/c. Bcgr
      (C.D2) mice, compared with congenic M. avium-susceptible BALB/c (Bcgs) animals.
      Although maximal granulocytosis values were not related to virulence of the
      inocula, the kinetics of the granulocytic response varied with the virulence of
      M. avium. Following infections by avirulent (rough) strains of M. avium, the
      peritoneal granulocytosis progressively declined in BALB/c and C3H/He mice. A
      similar decline in granulocyte number was observed in resistant C3H/He mice
      infected with virulent M. avium (smooth transparent strain). In both instances
      the decline in the peritoneal granulocytosis was associated with a progressive
      elimination of the inoculum. In the susceptible BALB/c mice, virulent M. avium
      strains induced progressive infection accompanied with a rapid decline in
      granulocyte number, whereas the infection with attenuated M. avium, which caused
      a chronic infection, induced persistent granulocytosis. The ability to recruit
      granulocytes following the intraperitoneal inoculation of a phlogistic substance
      (casein hydrolysate) was decreased in infected susceptible but not in infected
      resistant mice at 90 days of infection with virulent M. avium.

PMID- 1993358
TI  - Antibody-mediated demyelination in experimental allergic encephalomyelitis is
      independent of complement membrane attack complex formation.
AB  - The effects of decomplementation by cobra venom factor (CVF) on the pathogenesis
      of inflammation and demyelination in experimental allergic encephalomyelitis
      (EAE) and acute antibody-mediated demyelinating EAE (ADEAE) have been quantified
      histologically and immunocytochemically. In rats immunized with 50 micrograms of
      myelin basic protein in Freund's complete adjuvant containing 100 micrograms heat
      killed Mycobacterium tuberculosis H37Ra, clinical signs of EAE were completely
      suppressed by two injections of CVF given 9 and 12 days post-immunization.
      Suppression of clinical disease was associated with a dramatic reduction in peri
      vascular inflammation in the CNS, although immunohistochemical staining
      identified small numbers of infiltrating T cells and macrophages. In contrast,
      CVF treatment had no significant effect on the clinical severity of ADEAE and
      although C9 deposition within the CNS was virtually abolished, there was no
      statistically significant decrease in the extent of demyelination or
      inflammation. These observations indicate that in the absence of complement
      components C3 and C5 an antibody-dependent cell-mediated cytotoxic response plays
      an important role in the pathogenesis of antibody-mediated demyelination. The
      major role of the complement cascade in EAE appears to be the generation of pro
      inflammatory factors that enhance the inflammatory response within the CNS in
      animals facing a mild encephalitogenic challenge.

PMID- 1993359
TI  - Characterization of three monoclonal antibodies to membrane co-factor protein
      (MCP) of the complement system and quantification of MCP by radioassay.
AB  - MCP is a widely distributed regulatory glycoprotein of the complement system
      which binds C3b and C4b and has factor I-dependent co-factor activity. Monoclonal
      antibodies raised to lymphocytes (E4.3), chorionic microvilli (GB24) and an
      embryonal carcinoma cell line (TRA-2-10) recognize MCP (CD46). GB24 inhibited
      both the binding of MCP to its ligand iC3 and co-factor activity; E4.3 and TRA-2
      10 did not. The binding of GB24 to cells bearing MCP was not cross-inhibited by
      E4.3 or TRA-2.10, but TRA-2-10 blocked binding and displaced pre-bound E4.3.
      Using these antibodies, we developed a radioassay for quantifying the number of
      MCP molecules/cells. Human peripheral blood mononuclear (PBMC) and
      polymorphonuclear cells (PMN) had about 10,000 MCP cell; platelets had about
      600/cell, and no MCP was found on erythrocytes. Neoplastic hematopoietic cell
      lines, of myelocytic and T lymphocytic origin, had several-fold more (20-60,000)
      molecules cell than peripheral blood cells or B cell lines (about 12,000).
      Malignant epithelial cell lines. HeLa (about 100,000/cell) and HEp-2 (about
      250,000 cell) had the highest MCP expression of any cells examined. These
      monoclonal antibodies--especially GB24, which blocks MCP function--and the direct
      binding assay will facilitate the further analysis of the biology of this
      complement regulatory protein.

PMID- 1993361
TI  - Anti-nuclear antibodies of primary biliary cirrhosis recognize 78-92-kD and 96
      100-kD proteins of nuclear bodies.
AB  - The specificities of anti-nuclear antibodies (ANA) reacting with multiple nuclear
      dots (MND-ANA) present in about 15% primary biliary cirrhosis sera were studied
      by Western blot analysis with nuclear fractions from a human cell line.
      Reactivity with two broad bands of 78-92 kD and 96-100 kD of the insoluble
      fraction was present exclusively in MND-ANA-positive sera. Antibodies eluted from
      these proteins specifically retained the immunofluorescence reactivity of MND
      ANA. Immunomorphological analysis by a pre-embedding technique revealed that the
      antibody specifically binds to nuclear regions resembling in size and number
      nuclear bodies. Since these structures are absent in immature rate endometrial
      cell and can be induced by diethylstilbestrol, we tested MND-ANA by
      immunofluorescence on cryostat sections of uteri from hormone-treated and
      untreated immature rats. A strong reaction of nuclear dots was observed
      predominantly in endometrial cells of hormone treated rats. We thus conclude that
      MND-ANA present in primary biliary cirrhosis sera are directed against 78-92-kD
      and 96-100-kD nuclear proteins located in nuclear bodies.

PMID- 1993360
TI  - Detection of human and murine common idiotypes of DNA antibodies in tissues and
      sera of patients with autoimmune diseases.
AB  - The expression in tissue and serum of a panel of murine and human common DNA
      antibody idiotypes (Ids) (BEG 2, PR 4, F-423, I-402, II-28, IV-228, V-88) has
      been investigated. The murine V-88 Id was detected in eight out of 10 and the
      human BEG 2 Id in five out of 10 labial biopsies from patients with Sjogren's
      syndrome. The murine F-423, I-402 and IV-228 Ids were identified in one out of 10
      biopsies. In each case the pattern of staining was similar with staining of the
      acinar basement membrane and a cell population. Using double-labelling
      immunohistochemistry this cell population were identified as plasma cells. No
      staining was seen in four normal labial biopsies. The V-88 Id was detected on the
      epithelial aspect of the thickened basement membrane in three out of nine renal
      biopsies from patients with systemic lupus erythematosus (SLE). None of the other
      Ids (BEG 2, PR4, IV-228, F-423 or I-402) could be detected in renal tissue. None
      of the Ids were found in skin biopsies from SLE patients. Id V-88 may, like the
      16/6 Id to which it is phenotypically related, play a role in the pathogenesis of
      renal lesions in SLE. The BEG 2 Id could be detected in the serum of patients
      with rheumatoid arthritis (RA) and active untreated tuberculosis. Ids II-28, V-88
      and I-402 were elevated in serum from patients with Sjogren's syndrome and II-28
      Id in serum from patients with myositis and RA. None of the Ids were elevated in
      serum from patients with SLE. Apart from the BEG 2 Id, none of the Ids were
      elevated in serum from patients with tuberculosis or Gram-negative infections.
      The presence of murine Ids in human tissue and serum suggests that they are cross
      species idiotypes and have been conserved through evolution.

PMID- 1993362
TI  - Anti-idiotypes against anti-neutrophil cytoplasmic antigen autoantibodies in
      normal human polyspecific IgG for therapeutic use and in the remission sera of
      patients with systemic vasculitis.
AB  - Anti-neutrophil cytoplasmic antigen (ANCA) activity was inhibited in 15 out of 21
      sera from patients with acute systemic vasculitis following incubation with
      normal polyspecific IgG for therapeutic use (IVIg). ANCA antibodies reacted with
      IVIg through idiotypic-anti-idiotypic interactions, as shown in competitive
      binding assays using F(ab')2 fragments from IVIg and affinity chromatography of
      ANCA IgG on Sepharose-bound F(ab')2 fragments from IVIg. Co-incubation of sera
      from patients with acute systemic vasculitis with paired autologous remission
      stage sera also resulted in inhibition of ANCA activity in acute sera. Remission
      sera contain IgM and IgG capable of interacting with beta and or alpha idiotypes
      of ANCA IgG from acute sera. Anti-idiotypic IgM may account for the lack of
      expression of ANCA activity in whole serum from patients in remission from
      systemic vasculitis, which were found to contain high titres of ANCA IgG. These
      observations suggest that remission of systemic vasculitis is associated with the
      generation of anti-idiotypes against autoantibodies rather than the suppression
      of production of ANCA autoantibodies. IVIg may modulate the activity of systemic
      vasculitis in vivo.

PMID- 1993363
TI  - Detection of interleukin-6 and interleukin-1 production in human thyroid
      epithelial cells by non-radioactive in situ hybridization and immunohistochemical
      methods.
AB  - Human endocrine thyroid epithelial cells have been described to produce cytokines
      in vitro. In order to determine whether they do so in vivo during thyroiditis,
      parallel studies on mRNA expression with a non-radioactive in situ hybridization
      technique and immunohistochemical detection for the protein were performed on
      frozen sections of thyroid samples from autoimmune thyroiditis (Graves' disease
      and Hashimoto's thyroiditis), non-toxic goitre and normal thyroid tissue. cDNA
      probes were sulphonated and their hybridization with mRNA was detected with a
      sulphonyl-specific monoclonal antibody. This signal was amplified and visualized
      with the alkaline phosphatase-anti-alkaline phosphatase (APAAP) system. The
      protein products were detected with immuno-purified rabbit F(ab')2 antibody
      fragments recognizing recombinant human cytokines, visualized by the
      immunoperoxidase technique. Each sample was studied at the two levels. Both
      interleukin-6 mRNA and protein were found in the endocrine cells. There was no
      obvious difference between autoimmune thyroiditis and non-toxic goitre. However,
      normal thyroid epithelial cells produced less interleukin-6. Interleukin-1 alpha
      mRNA and its protein were found in epithelial cells from Hashimoto's thyroiditis
      samples, but not in the others, except one Graves' disease sample, in which only
      mRNA was detected. Interleukin-1 beta was not detected in these cells, its mRNA
      was only found in one of the Graves' disease samples. These cytokines were also
      detected in some infiltrating cells.

PMID- 1993364
TI  - Induction of tumour necrosis factor-alpha during haemodialysis. Influence of the
      membrane type.
AB  - Some of the secondary clinical effects induced by long-term haemodialysis in
      patients with end-stage renal failure have been related to an increased
      production of interleukin-1 (IL-1). We investigated the role of another cytokine
      which shares a number of biological properties with IL-1, tumour necrosis factor
      alpha (TNF-alpha). In long-term haemodialysed patients, we found at the beginning
      of the dialysis increased plasma TNF-alpha levels and enhanced monocyte capacity
      to produce TNF-alpha spontaneously ex vivo. Non-haemodialysed uraemic patients
      also presented increased plasma TNF-alpha levels. During dialysis with cellulose
      acetate (CA) or polysulphone (PS) membranes, plasma TNF-alpha levels and the
      spontaneous and lipopolysaccharide-induced production of TNF-alpha by monocytes
      remained at predialysis levels. In contrast, when cuprophane membranes were used,
      there was a significant increase in plasma TNF-alpha levels and in both
      spontaneous (10-fold) and lipopolysaccharide-induced (seven-fold) ex vivo TNF
      alpha production by monocytes. These results suggest that monocytes are
      stimulated during haemodialysis with the poorly biocompatible cuprophane
      membrane.

PMID- 1993365
TI  - Programmed cell death (apoptosis) in lymphoid and myeloid cell lines during zinc
      deficiency.
AB  - Three human cell lines of lymphoid (Molt-3 and Raji) or myeloid (HL-60) origin
      were maintained in vitro under zinc-sufficient or zinc-deficient conditions.
      Under these conditions, cell proliferation, viability and mode of death
      (apoptotic or necrotic) were assessed. All three cell types decreased their
      proliferative capacity and viability under conditions of zinc deficiency. Cell
      death in the HL-60 and Raji cultures occurred primarily via apoptosis, while most
      cells in zinc-deficient Molt-3 cultures died via necrosis. Apoptosis in zinc
      deficient cultures of HL-60 and Raji cells was characterized by a slow decline in
      culture viability as cells with condensed and fragmented nuclear DNA appeared.
      These morphological changes were accompanied by an increase in cell buoyant
      density, which allowed separation of viable apoptotic cells from their non
      apoptotic counterparts by means of percoll stepdensity gradients. Necrosis in
      zinc-deficient Molt-3 cultures was characterized by rapid loss of cell culture
      viability as these cells underwent direct lysis. Intact necrotic cells were
      easily identified by the flocculated state of their chromatin as well as the
      decreased basophilia of their cytoplasm. Analysis of DNA from apoptotic HL-60 and
      Raji cells revealed that internucleosomal DNA degradation, indicative of
      endogenous endonuclease activation, had occurred, whereas the nuclear DNA of
      necrotic Molt-3 cells remained relatively unfragmented. The different modes of
      cell death evoked may reflect the relative sensitivities of cells of these
      lineages to zinc levels in vivo.

PMID- 1993366
TI  - The role of the supraspinatus and infraspinatus muscles in glenohumeral
      kinematics of anterior should instability.
AB  - To investigate a socket mechanism responsible for controlling the kinematics in
      the statically positioned glenohumeral joint, a suprascapular nerve block was
      performed in 13 selected patients, with recurrent anterior instability and
      defects of the labrum. Kinematics were then documented by roentgenograms in four
      positions within the horizontal motion plane. Combined paralysis of the
      supraspinatus and infraspinatus muscles resulted in abnormal anterior translation
      in only two of 47 roentgenograms. Normal ball-and-socket kinematics were retained
      in the remaining 45 roentgenograms. The consistent arthroscopic findings were an
      undamaged glenoid articular surface with a detached or absent labrum. The injury
      to the labrum reduced the depth of the socket by one-half. The other one-half of
      the socket provided by the contour of the glenoid remained intact. A balanced
      muscle envelope was not required to maintain normal kinematics in selected,
      actively positioned, unstable shoulders. The retained glenoid depth was
      sufficient to produce the observed ball-and-socket kinematics. Further in vivo
      study of shoulder kinematics will be needed to clarify the interactive roles of
      the socket and muscle envelope in maintaining glenohumeral stability during the
      more demanding stresses during active shoulder motion.

PMID- 1993367
TI  - Superior humeral dislocation. A complication following decompression and
      debridement for rotator cuff tears.
AB  - Very large rotator cuff tears may be surgically irreparable and under such
      circumstances debridement of the edges of the cuff and bursal decompression may
      relieve pain. In this paper, four cases are described of the development of
      superior migration of the humeral head following a debridement and bural
      decompression. In all four patients attempts were made to repair the rotator
      cuff. In each case the repair failed and the humeral head migrated. Two of the
      patients had the humeral head replaced because of a fracture; in these patients
      the prosthesis displaced upwards. This serious complication may follow
      debridement and release of the subacromial bursa when rotator cuff repair cannot
      be achieved. In the correction of superior humeral migration, reestablishment of
      the roof of the bursa was carried out in two cases. This procedure appears
      effective and may be considered in the future for such cases.

PMID- 1993368
TI  - The profile view of the acromion.
AB  - A previously undescribed roentgenographic view shows the acromion in "profile." A
      sagittal view of the acromion outlines its bony architecture, specifically, the
      subacromial portion. This view is clinically useful in the perioperative
      evaluation of patients with impingement syndrome and can be especially revealing
      in some cases of persistent symptomatic impingement following previous
      acromioplasty. The view also provides an excellent perspective for
      roentgenographic examination of os acromiale. It is reproducible and relatively
      easy to obtain. The acromion is but one component of the subacromial arch, but
      this view is a valuable additional diagnostic tool to be used in evaluating the
      sometimes perplexing problem of impingement syndrome.

PMID- 1993369
TI  - The surgical treatment of severe comminuted intraarticular fractures of the
      distal radius with the small AO external fixation device. A prospective three-and
      one-half-year follow-up study.
AB  - Although fractures of the distal radius are very common, an optimal treatment has
      not been clearly delineated. This is a prospective study of 40 patients, mainly
      young and active adults, with comminuted and unstable intraarticular fractures of
      the distal radius. The end results of closed reduction and rigid fixation with
      the small AO external fixator includes 36 patients (90%) with excellent and good
      results. Roentgenograms of 33 of these patients showed accurate alignment of the
      healed fractures. Four patients (10%) had a fair functional result, with a
      partial restriction of the range of movement, although roentgenograms
      demonstrated good alignment of the healed fractures. The small AO external
      fixator is both a useful and convenient method for the reconstruction and
      treatment of comminuted intraarticular fractures of the distal radius.

PMID- 1993370
TI  - A semiinvasive method for articular Colles' fractures.
AB  - An external fixation device that allows limited motion of the wrist joint without
      disruption of the anatomic alignment was used for the articular Colles' fractures
      in this study. From July 1985 to April 1989 during a 45-month period, 87 patients
      with 90 articular Colles' fractures (three cases with bilateral involvement) were
      treated with a modified dynamic external skeletal device after a closed reduction
      in full supination of the forearm. Excellent anatomic reduction near 91% of the
      sound wrist as well as satisfactory functional results around 90.5% of the sound
      wrist were gained during the 24-month follow-up period. Forearm muscles exert
      compression forces on distal radial metaphyseal fractures throughout the healing
      period. Any procedure or device that cannot provide constant counterforce to the
      action of forearm muscles during fracture healing will result in the loss of
      anatomic reduction. Adequate distraction counter-force was provided by an
      external fixation device that was superior to other conventional methods because
      of its simple application, low rate of complications, and excellent anatomic and
      functional results.

PMID- 1993371
TI  - Diagnostic and operative arthroscopy of the wrist.
AB  - The evaluation and diagnosis of wrist disorders has traditionally been difficult
      and problematic. Ligamentous wrist sprains and their associated carpal
      instabilities, triangular fibrocartilage complex disruptions, and cartilage
      injuries have been virtually impossible to fully assess because of the inadequacy
      of current diagnostic techniques. Arthroscopy of the wrist allows a thorough
      evaluation of the soft-tissue structures and cartilaginous surfaces within the
      radiocarpal and midcarpal joints. In selected cases, wrist arthroscopy can be
      employed to surgically modify the intraarticular lesions and to assist in the
      planning of reconstructive operations.

PMID- 1993372
TI  - A comparison of intramedullary and extramedullary alignment systems for tibial
      component placement in total knee arthroplasty.
AB  - Fifty-two primary total knee arthroplasties (TKAs) using an intramedullary tibial
      jigging system to obtain ideal tibial alignment (90 degrees +/- 2 degrees) were
      compared with 62 TKAs using an extramedullary tibial jigging system. The Insall
      Burstein total knee system was used in all cases, and all femoral components were
      positioned with extramedullary jigs. Postoperative evaluation consisted of a
      standing, hip-to-ankle anteroposterior roentgenogram and measurement of the
      following angles: (1) femorotibial, (2) tibial component, (3) femoral component,
      and (4) mechanical axis. Ideal tibial component alignment using the
      intramedullary system was statistically superior to alignment achieved with the
      extramedullary system. All other angle comparisons showed no statistical
      significance.

PMID- 1993373
TI  - Anterior compartment syndrome of the thigh as a complication of blunt trauma in a
      patient on prolonged anticoagulation therapy.

PMID- 1993374
TI  - Intercondylar notch measurements with special reference to anterior cruciate
      ligament surgery.
AB  - The femoral intercondylar notch width was measured in 93 patients with chronic
      anterior cruciate ligament (ACL) insufficiency (Group 1), in 62 patients with an
      acute tear of the ACL (Group 2), and in 38 fresh anatomic specimen knees (Group
      3). In six of the specimen knees, further anatomic studies of the intercondylar
      notch were performed after tissue removal. The average intercondylar distance was
      16.1 mm in Group 1, 18.1 mm in Group 2, and 20.4 mm in Group 3. All differences
      were highly significant. The intercondylar notch was wider in the posterior part
      and had no crossing bony ridges but had generally concave walls, which provided a
      functional shelf for the ACL to insert on the lateral side. Significant
      osteophyte formation and stenosis of the anterior outlet of the intercondylar
      notch occur early in the ACL-deficient knee. A narrow anterior outlet of the
      intercondylar notch without osteophytes was also found in knees with an acute ACL
      rupture. At reconstruction of the ACL, notchplasty should be performed
      concomitantly.

PMID- 1993376
TI  - Dislocation of the knee.
AB  - The results of treatment for vascular and ligamentous injuries in 17 patients who
      suffered complete dislocation of the knee were reviewed. Eight patients had 23
      associated injuries. All nine patients who had injuries of the popliteal artery
      had arterial reconstruction with saphenous vein bypass grafts, which were
      successful in eight (89%). Intraoperative arteriography after vascular repair
      showed a narrowed anastomosis requiring revision in two (22%) of the nine
      patients and distal thrombi requiring removal in five (55%) patients. Delay in
      arterial repair was responsible for the one failure. Eleven patients had
      satisfactory results after early open ligament repair. The results were less
      favorable in the patients not treated with early ligament repair.

PMID- 1993375
TI  - Anterior-cruciate-insufficient knees treated with physiotherapy. A three-year
      follow-up study of patients with late diagnosis.
AB  - To evaluate a functional neuromuscular training program focusing on strength,
      endurance, postural control, and agility, 26 patients with a rupture of the
      anterior cruciate ligament (ACL) diagnosed late were examined before starting a
      training period and then followed for three years. During the study period, four
      of the patients had an ACL reconstruction. Twenty-two patients treated without
      surgery were satisfied with the improvement in their knee function and activity
      level after three to six months of physiotherapy. Compliance with the
      rehabilitation program was good and the improvement achieved on completion of the
      training period was maintained for three years in this group of recreational
      sportsmen and women. Quadriceps strength, functional knee score, activity level,
      and functional performance were all improved after training and were maintained
      during the follow-up period.

PMID- 1993377
TI  - Varus of the talus in the ankle mortise secondary to calcaneus fracture. A case
      report.
AB  - Varus displacement of the talus in the ankle mortise secondary to a calcaneus
      fracture was observed in a 33-year-old man. Similar to the calcaneus fracture
      dislocation, the mechanism involved inferior and medial displacement of the talus
      into the body of the calcaneus. The patient's ankle deformity was not corrected
      by a lateral ankle ligament reconstruction. Correction required a distraction
      subtalar bone block fusion. Successful reconstruction of the hindfoot after
      calcaneus fractures requires a careful analysis of the pathologic lesion. In this
      unusual case, correction required restoration of lost hindfoot bone structure.

PMID- 1993378
TI  - Local antibiotic delivery in the treatment of bone and joint infections.
AB  - Antibiotics can be delivered locally via an implantable pump to treat bone and
      joint infections. This is a completely closed system, and the pump is refilled
      percutaneously at intervals based on its flow rate. The use of this method is
      described in three specific clinical situations: (1) resistant osteomyelitis
      (patients with persistent infections despite previous therapy), (2) acutely
      infected arthroplasties (symptomatic for less than six weeks), and (3)
      chronically infected arthroplasties (patients infected more than six weeks). In
      all three clinical situations, hospitalization time was shortened, and high local
      and low systemic levels of antibiotic were obtained. There was only one incident
      of side effects to the antibiotic used. This method has been successful in
      obtaining long-term suppression of infection in 30 of 42 patients with resistant
      osteomyelitis, 30 of 37 patients with acutely infected arthroplasties, and seven
      of ten patients with chronically infected arthroplasties. The complication unique
      to this method of therapy is pump-site and catheter-site infections. This
      occurred in three patients with recalcitrant osteomyelitis and three patients
      with acutely infected arthroplasties.

PMID- 1993379
TI  - Epidemiology of primary osteogenic sarcoma in the San Francisco Bay Area of
      California.
AB  - This epidemiologic study represents an analysis of all registered new cases of
      osteogenic sarcoma (OGS) during the 14-year period from January 1973 to December
      1986 in five San Francisco Bay counties. Inclusion into the study was limited to
      patients who were diagnosed in the first three decades of life and who were
      residents within the Bay Area at the time of diagnosis. To determine
      epidemiologic characteristics of OGS, records on 96 patients from the Bay Area
      Resources for Cancer Control with histologically proven OGS were reviewed. The
      incidence of OGS was influenced by age, gender, and race, but none of the effects
      were statistically significant. A geographic variation in the incidence of OGS
      was discovered, although it was not statistically significant. The results are
      presented in support of a continued search for environmental variables that may
      someday reveal the etiologic factors of OGS.

PMID- 1993380
TI  - Spontaneous necrosis in osteosarcoma.
AB  - The percentage of necrosis in a primary osteosarcoma after the patient has
      received preoperative chemotherapy is prognostic and is usually used to select
      subsequent chemotherapy. However, the percentage of necrosis that occurs
      spontaneously, without preoperative chemotherapy, has not been adequately
      studied. The examination of histologic macrosections of 76 osteosarcomas from
      patients who had not received preoperative treatment and of 20 patients who had
      received preoperative chemotherapy revealed a significant difference in the
      percentage of necrosis. There was minimal spontaneous necrosis, but necrosis
      after preoperative chemotherapy was usually extensive. The larger the tumor, the
      greater the percentage of spontaneous necrosis; however, size did not correlate
      with the percentage of necrosis with preoperative chemotherapy. Survival among
      those patients who did not receive preoperative treatment correlated with the
      size and percentage of necrosis. Necrosis in an osteosarcoma in a patient who has
      received preoperative chemotherapy can be considered the result of chemotherapy
      and not a spontaneous event.

PMID- 1993381
TI  - Solitary fibromatosis of bone. A rare variant of congenital generalized
      fibromatosis.
AB  - Congenital generalized fibromatosis is part of the spectrum of the fibromatoses
      of infancy and childhood. The lesions are usually multiple and fibrous in nature.
      They may appear in virtually every organ outside the central nervous system.
      Congenital generalized fibromatosis can be limited to the skeleton and rarely
      manifests itself as a solitary bone lesion. Solitary osseous lesions often behave
      differently than multiple osseous lesions. Solitary lesions often do not regress
      without treatment and can have a high incidence of recurrence with less than
      marginal excision. Multiple osseous lesions often regress without treatment.

PMID- 1993383
TI  - A histologic and immunohistochemical study of calcium pyrophosphate dihydrate
      crystal deposition disease.
AB  - The articular cartilage, synovial membrane, and meniscus from ten patients who
      had calcium pyrophosphate dihydrate (CPPD) crystal deposition disease showed
      strong immunoreactivity for dermatan sulfate proteoglycan, Type I collagen, and S
      100 protein in hypertrophic chondrocytes around the crystals, their pericellular
      matrix, and deposits of the crystals. Electron microscopy revealed that small
      crystals were formed around the hypertrophic chondrocytes, especially in the
      degenerated matrix containing electron-dense granular materials and cellular
      debris. Chondrocytes of this kind were never observed in the articular tissue
      from ten patients who had osteoarthrosis. These hypertrophic chondrocytes with
      several unique immunohistochemical characteristics may initiate the formation of
      CPPD crystals.

PMID- 1993382
TI  - Muscle tissue reactions to implantation of bone matrix gelatin.
AB  - Histologic changes of muscle tissue in the early stage of heterotopic
      osteogenesis induced by syngeneic insoluble bone matrix gelatin (BMG) with bone
      morphogenetic protein in rats was observed by light and electron microscopy. BMG
      induced cartilage in muscle tissue by Day 7 after its implantation, woven bone by
      Day 10, and lamellar bone with bone marrow by Day 14. The new findings in this
      work include (1) the disappearance of the basement membrane of muscle fibers; (2)
      the activation of the satellite cells of muscle fibers; (3) the appearance of
      fibroblastlike cells that closely resembled activated satellite cells among the
      degenerated muscle fibers or on the surface of the BMG; and (4) the change of
      fibroblastlike cells to chondroblasts or osteoblasts. These findings suggest that
      intramuscular implantation of BMG caused the conspicuous disappearance of the
      basement membrane of the muscle fiber and may play a part in osteogenesis induced
      by BMG.

PMID- 1993384
TI  - A new model to assess tibial fixation in knee arthroplasty. I. Histologic and
      roentgenographic results.
AB  - A model to assess tibial fixation in knee arthroplasty is described. Eighteen
      mongrel dogs were implanted with a right tibial hemiarthroplasty. Implantation
      was of a press-fit, smooth implant (eight dogs) or a titanium alloy beaded device
      (ten dogs). Animals were studied at six, 12, 18, and 24 weeks. Roentgenographic
      and histologic analysis was performed for all implants. All animals were
      ambulatory. Roentgenographically, smooth implants showed progressive
      radiolucencies with increasing trabecular sclerosis under the implants. These
      changes were less prominent under the porous implants. Histologically, fibrous
      interfaces were identified focally under all implants but were thicker under
      smooth devices. Eighteen- and 24-week specimens showed substantial ingrowth into
      the porous pegs but minimal ingrowth into the porous plateau. Concurrent
      histologic and biochemical evaluation in dogs demonstrates the possible fate of
      implants in knee arthroplasty in human beings. As has been observed, histologic
      analyses suggest that clinically satisfactory results do not constitute evidence
      of stabilization by bone ingrowth.

PMID- 1993385
TI  - Paraosteoarthropathies of paraplegic patients by spinal cord lesion. Clinical and
      roentgenographic study.

PMID- 1993386
TI  - Bone growth factors.
AB  - Bone volume is determined by the relative rates of bone formation and bone
      resorption. Recent research in several laboratories suggests that growth factors
      may act locally to modulate bone formation by stimulating osteoblast
      proliferation and activity. A number of bone-derived growth factors have been
      isolated and characterized from bone matrix extracts and from media conditioned
      by bone cells and bone organs in culture. The growth factors found in bone matrix
      include insulinlike growth factors I and II, transforming growth factor-beta,
      acidic and basic fibroblast growth factor, platelet-derived growth factor, and
      bone morphogenetic proteins. Conditioned medium from bone cells contains several
      of these growth factors and also hematopoietic factors. These bone matrix-derived
      growth factors have different biologic activities, including mitogenic,
      differentiating, chemotactic, and osteolytic activities. Evidence suggests that
      bone cells produce substantial quantities of growth factors for extracellular
      storage in bone matrix. Apart from being produced for extracellular storage, it
      is possible that growth factors secreted by bone cells have acute effects on
      their neighboring osteoblastic cells, i.e., paracrine action, or on themselves,
      i.e., autocrine action. The release of matrix-stored growth factors by bone
      resorption may mean that growth factors act as delayed paracrine agents, e.g.,
      osteoblasts deposit growth factors in bone and later when these growth factors
      are released from bone via bone resorption, the growth factors stimulate
      osteoblast precursors to proliferate. The findings that bone is a storehouse for
      growth factors and that bone cells in culture produce and respond to bone growth
      factors suggest bone growth factors may act as potential determinants of local
      bone formation. This review is focused on the structure, regulation, and biologic
      actions of the known bone growth factors.

PMID- 1993387
TI  - A new model to assess tibial fixation. II. Concurrent histologic and
      biomechanical observations.
AB  - A tibial hemiarthroplasty model was designed to allow concurrent histologic and
      biomechanical analysis of the tibial implant-bone interface. In this study,
      micromotion was visually observed at the implant-bone interface of cemented and
      uncemented implants. Six dogs had staged bilateral implantation. Biomechanical
      analysis of three- and 12-month specimens was correlated with histologic analysis
      of the same specimen. Load transmission involved compression of trabecular bone
      and fibrous tissue at the interface. Failure of the interface occurred through
      cyclic fatigue and microfracture of trabeculae. Micromotion was seen at all
      interfaces, porous or smooth, cemented or uncemented. Displacement was greatest
      under an eccentrically loaded plateau. Micromotion at ingrown and cemented
      interfaces was because of trabecular compression. Uncemented smooth devices and
      uncemented porous devices with fibrous fixation of the plateau appeared unstable.
      The cemented implants and a single uncemented implant studied at 12 months showed
      no interface micromovement. The absence of micromovement in the uncemented
      implant was associated with subsidence and with ingrowth of 30% into the porous
      peg and porous plateau.

PMID- 1993388
TI  - Penicillin-induced hemolytic anemia and acute hepatic failure following treatment
      of tetanus in a horse.
AB  - Acute, severe hemolytic anemia occurred in a horse being treated for tetanus with
      intravenous penicillin and tetanus antitoxin. During treatment, the horse
      developed a positive direct antiglobulin test and a high titer (maximum 1:1024)
      of IgG anti-penicillin antibody. The horse recovered from the tetanus and
      penicillin induced hemolytic anemia, but later developed acute hepatic failure,
      probably resulting from the administration of equine origin tetanus antitoxin.

PMID- 1993389
TI  - Cutaneous hybrid cyst in four dogs.
AB  - Cutaneous hybrid cysts were recognized in 4 dogs. The lesions were solitary,
      asymptomatic, and occurred over the head, neck, proximal thigh, and lumbar
      region. These cysts were not accompanied by other disease processes, and did not
      recur following surgical excision. Histologically, the hybrid cyst is
      characterized by epidermal differentiation in its upper portion, and trichilemmal
      differentiation in its lower portion.

PMID- 1993390
TI  - Does continuing medical education work?

PMID- 1993392
TI  - Ovarian teratoma and granulosa cell tumor in two mares.
AB  - Simultaneous and successive occurrence of ovarian teratoma and granulosa cell
      tumor is reported in 2 mares. Simultaneous occurrence of the tumors may obscure
      clinical diagnosis. Whereas size, unilaterality, and the cystic nature of each
      may be similar, differentiating features include the potentially palpable
      presence of bone, cartilage, or teeth in teratoma, and the hormone-induced
      behavioral and reproductive effects of granulosa cell tumors. Thorough
      examination of surgical specimens may reveal the existence of a neoplastic
      process, previously obscured by the more obvious presence of another.

PMID- 1993391
TI  - Determination of skin threshold concentration of an aqueous house dust mite
      allergen in normal dogs.
AB  - Fifty-six healthy dogs with no known history of atopic disease to indoor
      allergens were skin tested with 6 different dilutions of an aqueous house dust
      mite extract. A concentration of 31.25 PNU/ml was found to be the maximum,
      nonirritating concentration. Thirty-two percent of the research dogs used had to
      be excluded because they failed to show reactions to any test dilution.

PMID- 1993393
TI  - Emphysematous gastritis in a horse.
AB  - A 12-year-old Morgan gelding was examined for colic of 3 days duration. Signs of
      depression, colic, diarrhea, and endotoxemia persisted despite aggressive medical
      therapy and surgical exploration. Culture results from gastric fluid and feces
      yielded many colonies of Clostridium perfringens. This organism also was
      recovered from peritoneal fluid 10 days after admission; consequently, the horse
      was euthanized. At necropsy, a localized gas-filled, necrotic stomach wall was
      found; many mucosal and submucosal gas blebs were visible. Culture of this tissue
      yielded Clostridium perfringens. Emphysematous gastritis is a fulminant infection
      of the stomach wall caused by gas-forming organisms that gain access to the
      submucosa via mucosal defects such as ulcers. This condition has been reported
      infrequently in people, and the case reported herein represents the first
      instance of emphysematous gastritis in the horse.

PMID- 1993395
TI  - Treatment of leptospirosis.

PMID- 1993394
TI  - Atlantoaxial malformation in a half-Arabian colt.
AB  - A 1-year-old half-Arabian colt was referred for evaluation of a cranial cervical
      abnormality. Physical examination revealed the left wing of the atlas to be more
      ventral than the right wing. A head tilt, with the pole deviated to the left, was
      present because of the malpositioned atlas. Neurologic examination identified
      symmetrical weakness, ataxia, and proprioceptive deficits in all four limbs.
      Radiographs of the cranial cervical region revealed fusion of the atlas and axis,
      and deviation of the atlantoaxial joint to the left of the median plane.
      Euthanasia was elected. Necropsy confirmed the radiographic findings. The atlas
      was rotated 20 degrees counterclockwise when viewed from the caudal aspect.
      Multifocal myelomalacia was present in the first and second cervical spinal cord
      segments. The malformation was believed to be due to a degenerative process or
      abnormal embryological development.

PMID- 1993397
TI  - Current concepts of oral medicine.

PMID- 1993396
TI  - Chronic lower-extremity ischemia. Part II.

PMID- 1993399
TI  - A dermatologic diary. Portrait of a practice.

PMID- 1993398
TI  - Nickel dermatitis in children.

PMID- 1993400
TI  - Clinical management of common oral lesions.
AB  - Soft tissue lesions are among the most commonly occurring pathologic conditions
      in the oral cavity. The causes of these lesions can vary from immunologic and
      viral reactions to underlying systemic disease, dermatologic lesions, or
      neoplasms. The diagnosis of these conditions is usually based on the history,
      clinical appearance, and results of diagnostic procedures such as smears,
      culture, or examination of biopsy specimens when indicated. This paper will
      discuss the diagnosis and management of some of the most commonly occurring oral
      lesions, such as recurrent aphthous ulcers, herpetic ulcers, and candidiasis.

PMID- 1993401
TI  - Diagnosis and management of commonly occurring oral vesiculoerosive disorders.
AB  - Vesiculoerosive disorders are often difficult to diagnose and manage. The oral
      cavity is often overlooked as a source of diagnostic signs of dermatologic
      disease. In some disorders, oral manifestations precede cutaneous signs by as
      much as one year. The authors describe the oral presentation and management of
      lichen planus, allergic stomatitis, pemphigus vulgaris, and cicatricial
      pemphigoid, to enable the physician to recognize, diagnose, and treat commonly
      encountered oral manifestations of dermatologic disease.

PMID- 1993402
TI  - Oral manifestations of human immunodeficiency virus infection.
AB  - Oral candidiasis, herpetic lesions, oral mucosal warts, human immunodeficiency
      virus-associated gingivitis and periodontitis, Kaposi's sarcoma, hairy
      leukoplakia, and non-Hodgkin's lymphoma are oral manifestations of infection by
      the human immunodeficiency virus. This paper will explain how to identify these
      lesions, their significance, and recommended treatments.

PMID- 1993403
TI  - Periodontal diseases: a review.
AB  - Periodontal diseases are a collection of disorders that may affect patients
      throughout life. The most common form of periodontal disease, gingivitis, which
      affects only the soft tissues, is seen in children, adolescents, and adults.
      Periodontitis, which destroys the bone supporting a tooth, is found more commonly
      in adults over the age of thirty-five but may be present in a variety of forms in
      children after three years of age. These diseases are caused by bacterial plaque
      but may be modulated by systemic diseases, immunologic compromise, heredity, and
      other contributing factors. Periodontal pathoses may be an indication of an
      underlying systemic condition such as leukemia or human immunodeficiency virus
      infection. The standard treatment of periodontal diseases is the control of
      intraoral plaque. This may be accomplished using mechanical, chemotherapeutic,
      and surgical means.

PMID- 1993404
TI  - Common dental conditions in patients receiving restorative dentistry.
AB  - Conditions that affect the dentition and the materials utilized to treat these
      conditions are often unfamiliar to the physician. Dental caries and missing teeth
      are processes routinely treated in dental practice. Recent improvements in dental
      materials and techniques permit the dentist to restore the dentition to allow for
      corrected form, function, esthetics, and patient comfort. This paper describes
      some of the common conditions that affect the dentition, and the modalities
      routinely used to treat them.

PMID- 1993405
TI  - The Joseph M. Mathews Oration. A plea for sanity. A comment on medical liability.

PMID- 1993406
TI  - Recovery from disturbed colonic transit time after alcohol withdrawal.
AB  - The effects of alcohol withdrawal on total and segmental transit time were
      evaluated in 20 chronic alcoholic subjects. After withdrawal, colorectal transit
      time significantly increased from 24.9 +/- 3.6 to 33.3 +/- 4.5 hours mean +/- SE
      (P less than 0.01). This was the result of an exclusive increase in rectosigmoid
      transit time from 2.8 +/- 0.7 to 9.8 +/- 2.1 hours (P less than 0.001). No
      variations were found in right or left colon transit time. Distal colonic
      motility is thus a crucial factor in the genesis of diarrhea in chronic alcoholic
      subjects.

PMID- 1993407
TI  - Water and electrolyte balance after ileoanal anastomosis.
AB  - Water and electrolyte balance was studied in 30 patients with ileoanal
      anastomosis and J pouch, 10 patients with conventional ileostomy, and nine
      nonoperated patients with quiescent ulcerative colitis. Serum electrolyte
      concentrations, daily urinary volume, and daily losses of sodium, potassium, and
      chloride were measured in all patients. Daily fecal weight and daily losses of
      sodium and potassium were analyzed in patients with ileoanal anastomosis or
      conventional ileostomy. Serum chloride in patients with ileoanal anastomosis was
      significantly lower (P less than 0.05) than in those with conventional ileostomy
      or in nonoperated patients. Daily urinary loss of sodium in nonoperated patients
      was significantly higher than in patients with ileoanal anastomosis (P less than
      0.01) or conventional ileostomy (P less than 0.05). Daily urinary loss of
      chloride in patients with ileoanal anastomosis was significantly lower (P less
      than 0.05) than in nonoperated patients. Daily fecal loss of potassium in
      patients with ileoanal anastomosis was significantly higher (P less than 0.05)
      than in those with conventional ileostomy. Daily urinary volume and fecal weight
      did not differ significantly in patients with ileoanal anastomosis or
      conventional ileostomy. The present study indicates that changes in water and
      sodium balance after ileoanal anastomosis are similar to those after conventional
      ileostomy but chloride balance is more altered after ileoanal anastomosis.

PMID- 1993408
TI  - Adaptive increase in peptide YY and enteroglucagon after proctocolectomy and
      pelvic ileal reservoir construction.
AB  - Functional results improve with time after proctocolectomy and pelvic ileal
      reservoir construction. We hypothesized that adaptive increases of circulating
      and tissue levels of the gut hormones peptide YY (PYY) and enteroglucagon may
      contribute to this improvement by slowing small bowel transit and increasing
      small bowel absorption. The specific aim of this study was to measure plasma and
      ileal mucosal concentrations of PYY and enteroglucagon in dogs 1 year after
      proctocolectomy and ileal reservoir-anal anastomosis. In the ileal reservoir
      dogs, postprandial PYY levels reached 238 +/- 31 pmol/liter compared with 93 +/-
      33 pmol/liter in sham operated controls (P less than 0.001). Postprandial plasma
      enteroglucagon levels reached 199 +/- 53 pmol/liter in reservoir animals and 52
      +/- 4 pmol/liter in controls (P less than 0.05). Tissue levels of PYY in the
      mucosa of the ileal reservoirs were 419 +/- 43 pmol/g compared with 133 +/- 23
      pmol/g in normal terminal ileum (P less than 0.0001). Enteroglucagon levels were
      also elevated in reservoir mucosa (193 +/- 21 pmol/g vs. 113 +/- 9 pmol/g in
      controls, P less than 0.05). These data demonstrate that postprandial and tissue
      levels of PYY and enteroglucagon increase in dogs 1 year after construction of
      ileal reservoirs. The adaptive increase in PYY would slow small bowel transit and
      the increase in enteroglucagon would promote mucosal growth, each contributing to
      the improved functional results.

PMID- 1993409
TI  - Assessment of "squamous cell carcinoma antigen" (SCC) as a marker of epidermoid
      carcinoma of the anal canal.
AB  - We measured squamous cell carcinoma antigen (SCC) in epidermoid carcinoma of the
      anal canal in 66 patients. Samples were taken at diagnosis, before treatment, and
      during follow-up; 353 samples were analyzed. The positive threshold was taken as
      2 ng/ml. At diagnosis, the sensitivity of the marker was 44 percent and its
      specificity 92 percent. In our series, the pretherapeutic level of SCC does not
      correlate with T as in Papillons' Clinical Staging System, but it does correlate
      with nodal invasion (P less than 0.05). It is of no prognostic value at the time
      of diagnosis. During follow-up, at relapse the level of SCC is 20.3 +/- 43 ng/ml.
      This increase is significant (P less than 0.01): the sensitivity of the marker is
      77 percent. In patients who have relapsed, development of the illness correlates
      with the level of SCC, which is of prognostic value (P less than 0.01). In
      conclusion, the level of SCC should be associated with the clinical follow-up of
      patients with epidermoid carcinoma of the anal canal.

PMID- 1993410
TI  - "Mini-perforation" of the colon--not all postpolypectomy perforations require
      laparotomy.
AB  - In a 10-year experience with 4,784 consecutive colonoscopic polypectomies, the
      need for operative intervention in just two of seven perforations indicates that
      patients with specially defined, limited perforations can usually be treated
      nonoperatively. This specific complication, which has been termed "mini
      perforation," is generally detected within 6-24 hours of polypectomy, and is
      characterized by local pain and tenderness, without signs of diffuse or spreading
      peritoneal irritation. Free intra-abdominal or retroperitoneal air on x-ray
      documents the actual perforation. Complete resolution of symptoms within 24-48
      hours confirms the diagnosis of "mini-perforation." Success depends on good bowel
      preparation for colonoscopy, and early recognition of perforation, with
      institution of bowel rest and intravenous antibiotics. The "mini-perforation"
      spontaneously closes, probably by omental adherence. Frequent serial clinical
      examinations are mandatory so that frank perforation with advancing peritonitis
      will be promptly recognized and treated surgically. An understanding of the three
      levels of cautery injury to the colon wall--"serosal burn," "mini-perforation,"
      and "frank perforation" are essential in managing the complications of
      colonoscopic polypectomy.

PMID- 1993411
TI  - Anorectal dysfunction in patients with urologic disturbance due to multiple
      sclerosis.
AB  - Anorectal function was evaluated in 11 patients with voiding dysfunction due to
      multiple sclerosis. In six patients with constipation, three also had symptoms of
      obstructed defecation and one patient was incontinent due to stercoral diarrhea.
      One patient was only fecal incontinent and one patient had obstructed defecation
      as the only symptom. Three patients had no anorectal symptoms. Anal manometry in
      the women compared with a control group revealed significant lower anal resting
      and squeeze pressures, although no significant difference of rectal sensation to
      distention with air was found. Pudendal nerve terminal latencies were obtained in
      seven patients and were all normal. In four patients latency could not be
      demonstrated due to poor contraction of the sphincter on stimulation of the
      pudendal nerve. Two of these patients were incontinent and two had both
      constipation and obstructed defecation. It is concluded that patients with
      voiding symptoms due to multiple sclerosis often reveal anorectal symptoms or
      motility disorders. Although anal sphincter function is reduced, fecal
      incontinence is not prevalent in this group. The reason for this lies probably in
      the fact that many of the patients are constipated, thus securing fecal
      continence.

PMID- 1993412
TI  - A comparison between single and double dose intravenous Timentin for the
      prophylaxis of wound infection in elective colorectal surgery.
AB  - A prospective, randomized, single-blind, controlled clinical trial was undertaken
      to determine whether two doses of systemic Timentin provided superior prophylaxis
      against postoperative sepsis in elective colorectal surgery compared with a
      single dose of the same antibiotic. Timentin, a combination of ticarcillin and
      clavulanic acid was administered intravenously (3.1 g) at the commencement of
      operation to all patients, and this was repeated after 2 hours in those patients
      randomized to receive a second dose. The wound infection rate was 11 percent in
      the 143 patients completing follow-up and receiving a single dose, and 13 percent
      in the 128 patients receiving two doses of Timentin (P greater than 0.05). The
      rates of postoperative septicemia 3 vs. 4 percent and intra-abdominal abscess 5
      vs. 8 percent were similar. Multivariate analysis of the factors likely to affect
      postoperative would infection rate demonstrated an association with the type of
      hospital, public or private, wound infection rate 16 and 6 percent, respectively
      (P less than 0.01), and the surgeon group defined by the number of patients
      contributed greater than 25 or less than 25, wound infection rate 6 and 18
      percent, respectively (P less than 0.05). We concluded that a single dose of
      intravenous Timentin was as effective as two doses for prophylaxis against
      surgical infection and that the surgeon group and the hospital in which the
      operation took place were statistically significant predictors of postoperative
      wound infection.

PMID- 1993413
TI  - The ileosigmoid knot.
AB  - The ileosigmoid knot (ISK) is a rare cause of intestinal obstruction.
      Unfamiliarity with the condition could have disastrous consequence at surgery.
      Over the past 20 years, we have encountered seven cases. Analyzing the data
      gathered from these, and on reviewing the literature, we found it possible to
      arrive at a preoperative diagnosis in two patients. Four patients were women, two
      of whom developed the obstruction in the postpartum period. One of the males was
      found to have an inflamed Meckel's diverticulum included in the knotting. The
      symptoms and the clinical findings were nonspecific. The characteristic x-ray
      findings of a double closed loop obstruction, was seen in only three patients.
      Resection of gangrenous bowel with anastomoses was feasible in four. Unlike in
      other series, primary anastomosis of the large gut was undertaken. There were two
      deaths early in the series. Guidelines to the management have been suggested.

PMID- 1993414
TI  - Polyamine levels in healthy and tumor tissues of patients with colon
      adenocarcinoma.
AB  - Tissue polyamine levels were determined in patients with colon adenocarcinoma to
      try to identify biochemical indicators able to characterize the growth and the
      metabolism of human solid tumors. Polyamine content was determined in the tumor
      and in the "healthy" mucosa sampled at different distances within the resection
      edges. For each patient the polyamine content in the tumor was compared with that
      in the mucosa. The results demonstrated that the spermidine concentration was
      higher in the tumor than in the healthy mucosa; the differences were
      statistically significant. However, spermine in the tumor increased to a lesser
      degree. No statistically significant differences were observed among these
      mucosae at different localizations, but the spermine concentration in the mucosa
      after the tumor showed values very close to those of the neoplasia.

PMID- 1993415
TI  - Crohn's disease and adenocarcinoma of the intestinal tract. Report of four cases.
AB  - Four patients with intestinal adenocarcinoma complicating Crohn's disease are
      reported. The youngest of the four patients was a 21-year-old female with a 9
      year history of Crohn's disease of the terminal ileum as well as of the entire
      colon. She developed mucus-producing moderately differentiated adenocarcinoma in
      the cecum. Of the remaining three patients with Crohn's disease, one presented an
      adenocarcinoma in the ascending colon, one in the rectum and the remaining one in
      the duodenum. All three colorectal adenocarcinomas originated in areas of high
      grade dysplasia and all four in areas with chronic transmural inflammation. The
      review of the literature indicates that a total of 174 small and large bowel
      cancers occurring in Crohn's disease have been recorded (including the four
      reported herein). The vast majority of the reported cases have been found in the
      North American subcontinent. Only in a few instances were bowel adenocarcinoma
      and Crohn's disease observed in the European continent. It is therefore
      remarkable that three of our four cases were seen within a period of 12 months.
      Interestingly, six patients having colorectal adenocarcinoma in association with
      Crohn's disease were recently reported from a single hospital in England. The
      question therefore arises whether our cases and those reported recently from
      England are unrelated and merely coincidental or whether carcinomas are now also
      affecting European CD patients. If the latter is the case, the surveillance
      policy for patients with CD should be reconsidered at this hospital.

PMID- 1993416
TI  - The role of fistulography in fistula-in-ano. Report of five cases.
AB  - A retrospective review of 27 patients undergoing anal fistulography is presented.
      The etiology of the 27 fistulas studied are as follows: cryptoglandular infection
      in 18, IBD in 7 (Crohn's 6, CUC 1), iatrogenic in 1, and foreign body perforation
      in 1. Twenty-six fistulograms revealed either direct communication with the anus
      or rectum, or abscess cavities/tracts, or both. Two fistulograms revealed no
      radiographic evidence of fistula (one patient had two fistulograms). In 13 of the
      27 patients (48 percent) information obtained from the fistulograms revealed
      either unexpected pathology (n = 7) or directly altered surgical management (n =
      6). We conclude that anal fistulography in properly selected patients may add
      useful information for the definitive management of fistula-in-ano.

PMID- 1993417
TI  - Colonic histoplasmosis in acquired immunodeficiency syndrome. Report of two
      cases.
AB  - Colonic histoplasmosis is a rare entity. There have been four previous reported
      cases within the population of patients with human immunodeficiency virus (HIV)
      infection. Because of the increasing incidence of HIV infection within regions
      where histoplasmosis is endemic, this condition may become more common.
      Gastrointestinal histoplasmosis has protean clinical manifestations, and symptoms
      are often nonspecific. Any patient with HIV infection who has unexplained GI
      symptoms should undergo evaluation for possible histoplasmosis. Aggressive long
      term amphotericin B therapy has been effective in HIV patients with
      histoplasmosis. Resection or diversion of symptomatic colonic strictures caused
      by histoplasmosis may be necessary in addition to medical therapy.

PMID- 1993418
TI  - Incarceration of colonoscope in an inguinal hernia. "Pulley" technique of
      removal.
AB  - Because of its relative safety, colonoscopy has become an accepted diagnostic and
      therapeutic procedure in the evaluation of patients with colorectal disorders.
      Many unusual complications of colonoscopy have been described, but only anecdotal
      reports of hernial incarceration have been published. We present a case of a
      right-sided hernial incarceration of the colonoscope that would not permit
      reduction of the hernia nor removal of the instrument by conventional means. The
      mechanism of incarceration, which dictates the size of hernia at risk for
      incarceration, is explained. The "pulley" technique, which was used to remove the
      instrument without surgical intervention, is described.

PMID- 1993419
TI  - A rare cause of colitis--Brucella melitensis. Report of a case.
AB  - Documentation of gastrointestinal lesions in Brucella infections is sparse. A
      case of Brucella melitensis type 3 infection accompanied by erosive lesions of
      the colon, observed by endoscopy and histopathologic examination, is reported.
      Such gastrointestinal lesions have not been described since 1934. Before 1934
      only postmortem observations are recorded.

PMID- 1993420
TI  - Chronic anal fissure. A new method of treatment by anoplasty.
AB  - Chronic anal fissure is a common condition usually treated by maximal anal
      dilatation or lateral subcutaneous sphincterotomy. The following method is based
      on a common surgical principal; to widen a stenosed tube a longitudinal incision
      is made across the stenosed area and this is sutured transversely as in
      pyloroplasty. This method of anoplasty is simple and appears to have no resultant
      complications. Further studies are necessary before its value can be established
      compared to the presently accepted methods of treatment.

PMID- 1993421
TI  - Clinical practice recommendations. American Diabetes Association 1990-1991.

PMID- 1993422
TI  - [The staging diagnosis of Hodgkin's disease. A comparison of laparotomy and
      noninvasive methods].
AB  - The diagnostic efficiency of modern noninvasive methods more and more puts into
      question the need for exploratory laparotomy to determine the stage of Hodgkin's
      disease. In 208 patients (122 men and 86 women; mean age 29 [14-62] years) pre-
      and postoperative findings as to stage of the abdominal disease were compared.
      All patients had first been examined by ultrasound and computed tomography,
      followed by laparotomy with splenectomy. Findings of lymphography were available
      for 171 patients. Gross and microscopic examination of the tissues obtained by
      splenectomy and lymphadenectomy, as well as liver biopsy provided different
      stages from the preoperative ones, which in 46 had been false-negative, and in 16
      false-positive. Spleen weight and involvement of the spleen with Hodgkin
      infiltration correlated only weakly with one another. In 38 of 41 patients with
      parapancreatic and splenohilar lymphnode involvement the spleen was also
      affected. These results indicate that regarding the stage of Hodgkin's disease,
      noninvasive methods so far do not achieve the validity of pathological
      examination obtained at exploratory laparotomy with splenectomy.

PMID- 1993423
TI  - [The therapy of lipid metabolic disorders].

PMID- 1993425
TI  - [The preservation of occupational medicine research documents].

PMID- 1993424
TI  - [The mechanisms of the resistance of malignant cells to cytostatics].

PMID- 1993426
TI  - [Iron deficiency].

PMID- 1993427
TI  - [Retinopathy in acute pancreatitis?].

PMID- 1993428
TI  - [Osler's disease].

PMID- 1993429
TI  - [The cardiotoxic side effects of 5-fluorouracil].

PMID- 1993430
TI  - [Cyclosporin in primary biliary cirrhosis].

PMID- 1993431
TI  - [Frequency of thyroid gland carcinoma in hyperthyroidism].
AB  - From 1980 to 1989, 226 patients (199 females, 27 males, median age 41 [18-76]
      years) underwent surgery because of clinical hyperthyroidism. 152 patients had
      autoimmune thyrotoxicosis, and 74 functional autonomy. Histological examination
      of resected thyroid tissue revealed carcinoma in 6 cases (2.6%): 3 (2%) in
      autoimmune hyperthyroidism, and 3 (4%) in functional autonomy. Five tumours
      fulfilled the criteria for occult papillary thyroid carcinoma (highly
      differentiated, less than 1.5 cm diameter). One woman had both a multilocular
      papillary carcinoma and a medullary carcinoma without proven metastases. In none
      of the cases was a malignant tumour suspected preoperatively from sonography or
      scintigraphy studies. In the patients with occult carcinomas, extended bilateral
      subtotal resection was regarded as curative. In the patient with papillary and
      medullary carcinoma, remaining thyroid therapy was given. One patient with
      Basedow's (Graves') disease and a papillary carcinoma of diameter 1.3 cm received
      radioiodine at her own request. She and the four remaining patients received
      suppression therapy (150-200 micrograms L-thyroxine daily), with frequent follow
      up. During follow-up for a mean period of 24 months (range 6-51 months) there
      were no metastases or tumour recurrences.

PMID- 1993433
TI  - [Successful directional coronary atherectomy after futile attempts at balloon
      dilatation].
AB  - Coronary arteriography revealed severe stenoses of the proximal part of the
      anterior interventricular branch with normal ventricular function in two patients
      (aged 42 and 38 years) with stable angina and ischaemia reaction in the exercise
      ECG. In the first patient it was a short spur-like 80% narrowing. But
      percutaneous balloon angioplasty failed to change the angiographic appearance. In
      the other patient there was an eccentric, apparently elastic, 90% stenosis, about
      10 mm long. Here, too, balloon angioplasty had failed. Subsequently directional
      coronary atherectomy in both patients achieved removal of the stenosis with
      lasting clinical improvement. Atherectomy should be considered in similar cases
      after failed balloon dilatation.

PMID- 1993432
TI  - [Carcinoembryonic antigen in serum and pleural fluid to distinguish between
      bronchial carcinoma and pleural mesothelioma].
AB  - The concentrations of carcinoembryonic antigen (CEA) were measured, partly
      retrospectively and partly prospectively, in 94 patients with diffuse malignant
      mesothelioma and in 79 with bronchial carcinoma and pleural involvement. Serum
      concentrations were measured in all patients, pleural-fluid concentrations
      additionally in 53 patients of the former and 39 of the latter group. The
      concentrations were significantly higher in those with bronchial carcinoma (P
      less than 0.001). The two groups could be distinguished by serum concentrations,
      using 5.2 ng/ml as the limit, with a sensitivity of 68%, specificity of 98% and a
      predictive value of 96%. Measurement of CEA in pleural fluid (at a limit of 4.5
      ng/ml) had a specificity of 94% and a positive predictive value of 90%,
      sensitivity being similar to that for serum. The negative predictive value for
      serum CEA concentration was 79%, for pleural fluid it was 81%. Thus in most cases
      measurement of CEA in serum and, to a lesser extent in pleural fluid, is a very
      simple method to exclude mesothelioma with a high degree of certainty. If the CEA
      concentration is below the stated level, either may be present.

PMID- 1993434
TI  - [Pulmonary renal syndrome. Favorable prognosis of immunologically mediated
      diseases through adequate diagnosis and therapy].

PMID- 1993435
TI  - [Determination of erythropoietin activity in serum. Methods, indications and
      interpretation of the data].

PMID- 1993436
TI  - [Reimbursement by private health insurance for treatment by physicians without
      residence].

PMID- 1993437
TI  - [Early recognition of type II diabetes].

PMID- 1993438
TI  - [Late motherhood and pregnancy outcome].

PMID- 1993439
TI  - [Glucocorticoids in AIDS-associated Pneumocystis carinii pneumonia].

PMID- 1993441
TI  - [The diagnosis in motility disorders of the stomach and small intestine].

PMID- 1993440
TI  - [Adrenomyeloneuropathy as a cause of Addison's disease].
AB  - A 25-year old male, with a 3-year history of spastic paraparesis and a
      disturbance of bladder emptying, developed Addison's disease (plasma ACTH 1250
      pg/ml, depressed cortisol values with loss of diurnal rhythm, potassium 6.8
      mmol/l, sodium 123 mmol/l) associated with a urinary tract infection. The
      suspected diagnosis of adrenomyeloneuropathy was confirmed by the finding of
      raised plasma long-chain fatty acid concentrations. The patient was immediately
      given 0.4 mg fludrocortisone as a bolus, followed by 0.1 mg daily maintenance
      therapy, the urinary tract infection having already been successfully treated.
      Substitution therapy with hydrocortisone was also initiated (starting dose 30-20
      10 mg daily, maintainance dose 20-10-5 mg daily). As a result, the electrolyte
      concentrations returned to normal and the neurological features improved. A
      family study was undertaken to determine whether the adrenomyeloneuropathy was an
      X-linked recessive form. Both the symptom-free mother (carrier) and the 19-year
      old brother, who had suffered from Addison's disease since the third year of
      life, had raised plasma long-chain fatty acid concentrations. Both brothers were
      started on a diet low in long-chain fatty acids. Estimation of long-chain fatty
      acids is indicated in boys or young adult males with peripheral neuropathy or
      Addison's disease of uncertain aetiology.

PMID- 1993443
TI  - [Treatment against the will of the patient].

PMID- 1993442
TI  - [Thiazide diuretics and calcium metabolism].

PMID- 1993444
TI  - [What is not essential in the diagnosis of coronary heart disease?].

PMID- 1993445
TI  - [Normal cell proliferation and carcinogenesis].

PMID- 1993446
TI  - Epidemiological study of Salmonella enteritidis strains of animal origin in
      Belgium.
AB  - Since 1987, the number of cases of salmonellosis caused by Salmonella enteritidis
      has considerably increased in Western Europe. Comparison of endemic animal
      strains isolated in Belgium from 1976-84 with strains isolated from 1987 on shows
      that the strains which cause the current epidemic have no features distinguishing
      them from the previously-isolated strains and that furthermore, they do not
      constitute a bacterial clone. They belong to 13 different lysotypes and in most
      cases remain sensitive to antibiotics. Nevertheless, the lysotype 33 (which
      belongs to the phage type 4 has increased significantly. It encompasses 37% of
      the animal strains isolated in Belgium from 1987-9, but only 7% of the strains
      isolated from 1976-84. It is worth noting that the endemic as well as the
      epidemic strains contain a virulence plasmid sharing sequence similarities with
      the FIB and FIIA plasmid replicons and with the VirA and VirB virulence regions
      of the S. typhimurium virulent plasmid: pIP1350.

PMID- 1993447
TI  - The changing ecology of hospital bacteria and the selective role of
      cephalosporins.
AB  - More than 12,800 clinical isolates from 115,373 in-patient specimens obtained at
      the Sir Charles Gairdner Hospital, Perth, Western Australia, were identified and
      analysed statistically for relationships with usage of three generations of
      cephalosporins over the 5-year period from July 1984 to June 1989. A positive
      relationship between cephalosporin usage and significantly increasing isolation
      rates for those species capable of producing chromosomal beta-lactamases was
      observed. Simultaneously, a small increase in the isolation frequency of non
      chromosomal beta-lactamase-producing strains was noted and no correlation with
      cephalosporin usage was demonstrated. The trend toward predomination in the
      hospital environment of strains possessing substantial cephalosporin resistance
      has implications for future antimicrobial policy, choice of empiric therapy and
      the predictive value of standard antimicrobial susceptibility tests.

PMID- 1993448
TI  - Absence of epidemicity of severe leptospirosis in Barbados.
AB  - The possibility of micro-epidemics of severe leptospirosis occurring on the
      island of Barbados was investigated by examining the space-time clustering of the
      disease in 212 laboratory-confirmed cases admitted to Queen Elizabeth Hospital,
      Bridgetown, over a 7-year period. A series of 109 patients with symptoms
      compatible with leptospirosis but shown to be otherwise by laboratory examination
      were also examined for comparison. No significant space-time clustering was found
      among the leptospirosis cases, indicating no evidence for micro-epidemics. By
      comparison, statistically significant clustering was apparent among the smaller
      non-leptospirosis series. Possible explanations for the absence of observed micro
      epidemics of leptospirosis are discussed.

PMID- 1993449
TI  - Listeria faecal carriage by renal transplant recipients, haemodialysis patients
      and patients in general practice: its relation to season, drug therapy, foreign
      travel, animal exposure and diet.
AB  - About 2.3% (16/700) of faecal specimens from renal transplant recipients and
      patients having home haemodialysis as well as patients attending their general
      practitioners with symptoms of gastroenteritis yielded Listeria species 40% of
      positive faeces contained more than one Listeria species or serovar. The
      proportion of positive specimens was similar in all three patient groups.
      Listeria were isolated from 5.6% (10/177) of renal transplant recipients on one
      or more occasions over the period of a year. The commonest species was L.
      monocytogenes and type 4b the commonest serovar. Carriage was more common in July
      and August than other times of year, and less than 28 weeks in duration. In renal
      transplant recipients carriage was positively related to treatment with
      ranitidine, consumption of more than three types of cheese in the previous 20
      months, and consumption of English cheddar cheese more than once per week.

PMID- 1993450
TI  - Antibiotic resistance among Salmonella from human and other sources in New
      Zealand.
AB  - Of 2210 salmonella isolates referred to the New Zealand Communicable Disease
      Centre for epidemiological surveillance during 1987, 147 (6.7%) were resistant to
      one or more of 10 antibiotics. Resistance to streptomycin was most common (4.5%),
      followed by sulphamethoxazole (3.4%), tetracycline (3.3%), ampicillin (1.5%), and
      kanamycin (1.4%). Resistance to cephalothin, chloramphenicol, gentamicin and
      trimethoprim occurred in less than 1% of isolates. There was no resistance to
      norfloxacin. Isolates from human sources were significantly (P less than 0.001)
      more resistant (10%) than those from other sources (3.2%). The majority of
      resistant isolates were resistant to more than one antibiotic, but
      multiresistance to five or more antibiotics occurred only among human isolates.
      Comparison of these results with data from earlier years shows that there has
      been little change in the incidence of resistance among salmonella in this
      country over the last 10 years. The prevalence of antibiotic resistance among
      salmonella in New Zealand is low relative to many other countries.

PMID- 1993451
TI  - Distribution of Salmonella enteritidis phage types in Canada.
AB  - The distribution of Salmonella enteritidis phage types in Canada is described;
      606 of 674 strains examined were of human origin. Typable strains of all sources,
      constituted 99.6% (671/674) of all strains examined, and were representative of
      15 different phage types. Five phage types (8, 13, 4, 13a and 1) accounted for
      92.4% of the total. Phage type 8 consistently showed the highest incidence in
      human (69.96%) and non-human (72.05%) sources and appeared to be the most common
      in North America. Phage type 4, the most prevalent in the UK, is infrequent in
      Canada (38/674). The distribution of phage types showed regional variation among
      infrequent phage types, whereas the common type, 8, was observed in different
      frequencies in all provinces. Examination of 29 outbreaks of S. enteritidis
      representing 254 isolates for humans revealed 5 different phage types, the
      highest number of outbreaks (11) were type 8. A study of these outbreaks and the
      animal-host-associations of the common phage types, 8 and 13, indicated that
      contaminated poultry appeared to be the most common source of human infection in
      Canada.

PMID- 1993452
TI  - Variation in time and space of non-outbreak Legionnaires' disease in Scotland.
AB  - The main aim of this study was to measure and explain geographic variations in
      the incidence of Legionnaires' disease in Scotland, particularly to help
      understand the source of non-outbreak infection. Between 1978 and 1986 the
      overall mean annual incidence rate was 7.9 per million (range 3.1-20.2), and for
      non-outbreak, non-travel cases it was 5.6. There were geographical variations by
      health board, by city and within cities, e.g. the mean annual incidence rate per
      million for non-travel, non-outbreak disease was 1.2 in Tayside Health Board, 3.7
      in Lanarkshire, 5.6 in Lothian and 14.4 in Greater Glasgow. In Greater Glasgow
      Health Board non-travel cases lived in and around the city centre and in some
      postcode sectors there, the mean annual incidence rate exceeded 100. Travel
      related cases lived in peripheral areas. These variations could not be explained
      by differences in access to and use of diagnostic services, surveillance, or host
      susceptibility (as reflected by socioeconomic status and frequency of other
      respiratory disease). The explanation probably lay in environmental factors,
      though differences in agent virulence were not excluded. The two main conclusions
      are, that non-outbreak cases were not truly sporadic, and that the space-time
      variations in incidence support the hypothesis that cooling towers were an
      important source of infection for non-travel, non-outbreak cases. If so such
      infection is potentially preventable.

PMID- 1993453
TI  - Detection of novel trimethoprim resistance determinants in the United Kingdom
      using biotin-labelled DNA probes.
AB  - Two collections of trimethoprim R plasmids, isolated from strains of Escherichia
      coli during 1978-83 and 1987-8 respectively, were retrospectively screened with
      specific biotinylated DNA probes for the presence of genes encoding particular
      DHFR enzymes. The results confirmed that the type I DHFR gene was the predominant
      plasmid-encoded gene conferring trimethoprim resistance in strains of E. coli
      from the Nottingham area of the UK, but indicated that genes encoding the more
      recently recognized types of DHFR enzymes had appeared in the bacterial gene pool
      and could be recognized with increased frequency in the latter plasmid
      collection. This was particularly true of the type IIIa and type VII enzymes
      which together accounted for 27% of the trimethoprim R plasmids examined in 1987
      8.

PMID- 1993454
TI  - Cell-surface hydrophobicity of Staphylococcus saprophyticus.
AB  - The cell-surface hydrophobicity of 100 urinary isolates of Staphylococcus
      saprophyticus, cultured from symptomatic females in the general population, was
      assessed using a two-phase aqueous:hydrocarbon system. Relatively strong cell
      surface hydrophobicity was exhibited by 79 isolates using the criteria employed,
      while only 2 of the remaining 21 isolates failed to demonstrate any detectable
      hydrophobicity. Cell-surface hydrophobicity may be a virulence factor of S.
      saprophyticus, important in adherence of the organism to uroepithelia.
      Additionally, the data support the concept that cell-surface hydrophobicity may
      be a useful predictor of clinical significance of coagulase-negative
      staphylococci isolated from clinical sources.

PMID- 1993455
TI  - Campylobacter diarrhoea and an association of recent disease with asymptomatic
      shedding in Egyptian children.
AB  - A hospital-based case-control diarrhoea survey was conducted in Cairo, Egypt to
      determine the age-specific frequency of campylobacter infection among diarrhoeic
      and non-diarrhoeic children aged new born to 5 years. Campylobacter was the most
      common bacterial enteropathogen isolated from diarrhoeic stools. The overall
      prevalence of campylobacter isolations was 25.9% from stools of 143 diarrhoeic
      children compared to 15.2% of 132 non-diarrhoeic control children (P = 0.028)
      during the 4-month period of study. Children less than 1 year of age were at
      greatest risk of campylobacter infection with 32.6% of diarrhoeic patients
      culture positive, compared to 14.3% of controls. Asymptomatic shedding in
      controls was positively associated with a recent diarrhoeal episode (P = 0.019)
      and may be an important source of new infections.

PMID- 1993458
TI  - Plasmodium yoelii: quantification of the exoerythrocytic stages based on the use
      of ribosomal RNA probes.

PMID- 1993457
TI  - Inflammatory status and preerythrocytic stages of malaria: role of the C-reactive
      protein.
AB  - In the acquisition of protection against malaria, the role played by nonspecific
      factors, some being part of the cascade effect of cytokines, has to be
      considered. The C-reactive protein, a major acute phase reactant secreted by
      interleukin-1 stimulated hepatocytes, has an effect on the hepatic development of
      Plasmodia, both by preventing penetration of the sporozoite into the hepatocyte
      and by blocking parasite division through an antibody-like effect. This latter
      effect confirms the potential interest of targeting the uninuclear form of the
      parasite. Nevertheless, C-reactive Protein alone does not account for all the
      effects of the inflammatory response, other reactants from both serum and
      hepatocytes are also involved.

PMID- 1993459
TI  - Entamoeba histolytica: recognition of alpha- and beta-galactose by the 260-kDa
      adherence lectin.

PMID- 1993456
TI  - Waterborne transmission and the evolution of virulence among gastrointestinal
      bacteria.
AB  - Diarrhoeal diseases are primary contributors to millions of deaths annually. Yet,
      little is known about the evolutionary reasons for the differences in virulence
      among gastrointestinal pathogens. Applying the comparative, cost/benefit approach
      of evolutionary biology this paper proposes that waterborne transmission should
      favour evolution towards high virulence. This hypothesis is supported by a cross
      specific test, which shows that waterborne transmission is strongly correlated
      with the virulence of bacterial gastrointestinal pathogens of humans. Alternative
      explanations of this correlation are not supported by available data. These
      findings bear on public health policy because they draw attention to a previously
      unrecognized long-range benefit gained from purification of water supplies;
      diarrhoeal pathogens may evolve to lower levels of virulence.

PMID- 1993460
TI  - Toxoplasma gondii--new advances in cellular and molecular biology.

PMID- 1993461
TI  - Polyamine metabolism in some helminth parasites.
AB  - Polyamine levels of some helminth parasites were analyzed by reverse phase HPLC
      of benzoyl derivatives. Setaria cervi, Acanthocheilonema viteae, Hymenolepis
      nana, H. diminuta, and Ascaridia galli contained higher levels of spermine than
      spermidine while in Ancylostoma ceylanicum and Nippostrongylus brasiliensis the
      spermidine levels were higher than spermine; putrescine was either absent or
      present in minor quantities. The enzymes of polyamine biosynthesis viz.,
      ornithine decarboxylase, S-adenosyl methionine (SAM)-decarboxylase, and arginine
      decarboxylase were present in very low to negligible amounts in all the parasites
      examined. A. ceylanicum exhibited high activity of ornithine amino transferase
      (OAT) and catalyzed appreciable decarboxylation of ornithine. The ornithine
      decarboxylating activity of A. ceylanicum was localized in the particulate
      fraction containing mitochondria, not inhibited by alpha-difluoromethyl
      ornithine, the specific inhibitor of ornithine decarboxylase (ODC), but inhibited
      in the presence of glutamate, suggesting the involvement of mitochondrial OAT
      rather than a true ODC in ornithine decarboxylation in this parasite. Significant
      activity of polyamine oxidase was also detected in helminth parasites. The
      absence of polyamine biosynthesizing enzymes in helminth parasites suggests their
      dependence on hosts for uptake and interconversion of polyamines, providing a
      potential target for chemotherapy.

PMID- 1993462
TI  - Hymenolepis nana: adoptive transfer of protective immunity and delayed type
      hypersensitivity response with mesenteric lymph node cells in mice.
AB  - A marked degree of footpad swelling was observed in BALB/c mice infected with
      Hymenolepis nana eggs, when soluble egg antigen was injected into their footpads
      4 to 21 days after the egg infection, indicating delayed type hypersensitivity
      responses in infected mice. Adoptive transfer with mesenteric lymph node cells
      from donor mice (BALB/c strain; +/+) infected with eggs 4 days before cell
      collection could confer this hypersensitivity to recipient nude mice (BALB/c
      strain; nu/nu). These mesenteric lymph node cells were then divided into two
      fractions, blast-enriched and blast-depleted cells, by density gradient
      centrifugation with Percoll. The recipients intravenously injected with the blast
      depleted cell fraction showed a marked increase in footpad thickness, whereas the
      intravenous transfer of the blast-enriched cell fraction resulted in an
      insignificant increase in footpad thickness. The transfer of the blast-enriched
      cell fraction, but not of the blast-depleted cell fraction, conferred a strong
      adoptive immunity on syngeneic recipient nude mice, when the immunity transferred
      was assessed by examining cysticercoids developed in the intestinal villi on Day
      4 of challenge infection. The lack of delayed type hypersensitivity response in
      mice that received the blast-enriched cell population was not due to a lack of
      the capacity of the cells to induce the response, because the cells were capable
      of inducing a significant increase in thickness of footpads of normal mice when
      these cells were locally injected into the footpad together with soluble egg
      antigen.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1993463
TI  - Plasmodium berghei: ionic regulation and the induction of gametogenesis.
AB  - The role of ionic regulation in the induction of gametogenesis of Plasmodium
      berghei at 20 degrees C was investigated. A potent inhibitor of Na+/H+ exchange,
      amiloride, strongly inhibited exflagellation and subsequent ookinete formation
      induced by RPMI 1640 with 10% fetal calf serum at pH 8.0, whereas Na+ or K+
      channel inhibitors, H(+)-ATPase inhibitors, and a protonophore had no significant
      effect. Amiloride-treated 'activated' microgametocytes synthesized DNA to levels
      consistent with the expected 8C, but failed to develop further. These results may
      suggest that an increase in intracellular pH induced by Na+/H+ exchange plays an
      important role in the induction of gametogenesis by cultivating at pH 8.0 and 20
      degrees C. Cultivation at pH 8.0 and 37 degrees C did not induce the development,
      and microgametocytes remained as nonactivated forms, having the DNA content of
      1.5C. By culturing at pH 7.3 and 20 degrees C, however, most of microgametocytes
      finished synthesis of DNA up to the 8C level, but ceased development at various
      stages. Additionally, exflagellation occurred in a simple medium composed of
      buffered saline with 10 mM glucose. Glucose was indispensable for exflagellation,
      presumably acting as an energy source. Exflagellation induced by this solution
      was also inhibited by amiloride. It is therefore suggested that the induction of
      microgametogenesis may be composed of two distinct mechanisms, one is a
      temperature-dependent DNA synthesis and the other is a pH-dependent control of
      developmental events leading to microgamete assembly and exflagellation.

PMID- 1993464
TI  - Trypanosoma cruzi: shedding of surface antigens as membrane vesicles.
AB  - Tissue culture-derived trypomastigotes from Trypanosoma cruzi spontaneously shed
      surface antigens into the culture medium. The shedding is a temperature- and time
      dependent phenomenon and is independent of the presence of proteins or immune
      serum in the medium. The analysis of this process in four strains (Y, YuYu, CA1,
      and RA) showed differences in the amounts of polypeptides released. However, for
      all strains the liberation of the entire set of surface polypeptides ranging in
      molecular mass from 70 to 150 kDa was observed. Biochemical and electron
      microscopic data strongly suggest that most of the surface antigens are released
      as plasma membrane vesicles, ranging from 20 to 80 nm in diameter.

PMID- 1993466
TI  - Attachment of Trypanosoma cruzi trypomastigotes to receptors at restricted cell
      surface domains.
AB  - We have used glutaraldehyde-fixed target cells to study the attachment phase of
      cell invasion by live trypomastigotes of Trypanosoma cruzi, and determined that
      attachment is polarized and receptor-mediated. T. cruzi trypomastigotes bind much
      less efficiently to confluent epithelial cells, which are polarized, than to
      sparse epithelial cells. When the tight junctions of confluent epithelial cells
      are disrupted by removing Ca2+ from the incubation medium before glutaraldehyde
      fixation, binding of T. cruzi increases. T. cruzi also shows preference for
      attachment underneath cells or to the edges of cells. The binding occurs within a
      few minutes, is saturable, and is influenced by the parasite developmental stage.
      Fab fragment derived from monoclonal antibodies that immunoprecipitate a 160-kDa
      molecule present only on the surface of trypomastigotes inhibit adhesion to fixed
      and live cells. Future characterization of the target cell receptors for this
      molecule and the use of fixed target cells should facilitate studies of the
      mechanisms involved in the initial interaction of T. cruzi with its host cells.

PMID- 1993467
TI  - Plasmodium cynomolgi: immunization of a rhesus monkey with exoerythrocytic stages
      cultured in autologous hepatocytes.
AB  - To investigate the immune response to exoerythrocytic stages of malaria
      parasites, a rhesus monkey was immunized with autologous primary hepatocyte
      cultures infected with 7-day-old liver stage parasites of Plasmodium cynomolgi. A
      primary antibody response against EE stage antigens was obtained, and boosted
      after injection of homologous viable sporozoites. Antibodies directed against
      sporozoites and blood stages were also detected. The polyvalent immune response
      observed demonstrates the antigenicity of the liver stages and suggests their
      involvement in the general immune response against malaria.

PMID- 1993465
TI  - Trypanosoma cruzi: cellular and antibody response against the parasite in mice
      immunized with a 19-amino acid synthetic peptide.
AB  - Several monoclonal antibodies were prepared against the flagellar fraction of
      Trypanosoma cruzi epimastigotes (Tulahuen strain, stock Tul 2). One of them, FCH
      F8-4, has previously shown biologic activity against the parasite (complement
      mediated lysis and neutralization of the trypomastigote infectivity).
      Immunopurified antigens using this monoclonal antibody elicited a protective
      immune response in mice. Two recombinant cDNA clones were detected with this anti
      flagellar fraction monoclonal antibody on a lambda gt11 expression library
      prepared from T. cruzi epimastigote mRNA. The insert of one of these cDNA clones,
      lambda(FCH-F8-4)1 (150 bp) coded for a 19-amino acid peptide
      (PAFLGCSSRFSGSFSGVEP). This insert hybridized with a 5.0-kb mRNA from
      epimastigotes. The beta-galactosidase fusion protein was produced in lysogenic
      bacteria. The monoclonal antibody recognized the epitope present in the fusion
      protein after western blotting of the crude lysate. A synthetic peptide (SP4)
      containing the complete sequence of lambda(FCH-F8-4)1 was constructed on solid
      phase. This peptide was able to inhibit the ELISA reactivity (in a range from 13
      to 52%) of flagellar fraction immunized mouse sera and when administered (coupled
      to KLH or alone) to BALB/c mice with Bordetella pertussis as adjuvant, it induced
      a humoral and cellular immune response which was detected by ELISA,
      immunofluorescence, blotting, and DTH reactions against T. cruzi antigens. The
      immune response obtained indicates that this synthetic peptide resembles the
      parasite antigen conformation and could be useful for diagnosis purposes or be
      able to elicit immunoprotection against T. cruzi infection.

PMID- 1993468
TI  - Toxoplasma gondii: membrane structure differences between zoites demonstrated by
      freeze fracture analysis.

PMID- 1993469
TI  - Chloroplast transit peptides. The perfect random coil?
AB  - Structural analysis of chloroplast transit peptides (cTPs), including secondary
      structure prediction and analysis of 'cTP-like' peptides of known 3D structure,
      suggests that cTPs are essentially flexible peptides devoid of regular secondary
      or tertiary structure. It is proposed that cTPs may be designed to interact with
      a succession of different chaperones on the chloroplast protein-import pathway.

PMID- 1993470
TI  - Characterization of phospholipase A2 from the venom of Horned viper (Cerastes
      cerastes).
AB  - Phospholipase A2 has been purified from the venom of Horned viper (Cerastes
      cerastes) by gel permeation chromatography followed by reverse-phase HPLC. The
      primary structure was established by sequence analysis of the intact protein and
      its enzymic peptides. The structure has 120 residues, properties like other group
      IIB phospholipases, but only 45-55% identity with the enzyme from other viperid
      species, and large variations even within the species (26% residue differences at
      known positions in another form).

PMID- 1993471
TI  - Studies on the distribution of cellular myosin with antibodies to isoform
      specific synthetic peptides.
AB  - Antisera were produced against two synthetic peptides having sequences specific
      for cellular myosin heavy chains from human macrophages (peptide IIA) and bovine
      brain (peptide IIB). Immunoblots of tissue extracts were made with these
      antibodies, and they showed that mammalian cells have at least three distinct
      cellular myosin heavy chain isoforms. Two of the isoforms (MIIB1 and MIIB2) were
      recognized by antibodies against the peptide IIB, and the other (MIIA) by the
      anti-peptide IIA antibodies. Polyclonal anti-platelet myosin antibodies
      recognized the MIIA isoform, but did not recognize MIIB1 or MIIB2. The isoforms
      were expressed in a tissue-specific pattern; the MIIB1 isoform was found only in
      brain.

PMID- 1993472
TI  - Molecular analysis of revertants from a respiratory-deficient mutant affecting
      the center o domain of cytochrome b in Saccharomyces cerevisiae.
AB  - In bc complexes, cytochrome b plays a major role in electron transfer and in
      proton translocation across the membrane. Several inhibitor-resistant and
      respiratory-deficient mutants have already been used to study the structure
      function relationships of this integral membrane protein. We describe here the
      selection and the molecular analysis of revertants from a thermo-sensitive mit
      mutant of known nucleotide changes. Among 80 independent pseudo-wild type
      revertants screened by DNA-labelled oligonucleotide hybridization, 33 have been
      sequenced. Eight suppressor mutations, affecting a region critical for both the
      function and the binding of center o inhibitors (end of helix C) were identified.
      Two of them were found to be more resistant to myxothiazol.

PMID- 1993473
TI  - The same myosin isoforms are found in the female and male sexually dimorphic
      levator ani muscle of the rat, but their postnatal transitions are not
      synchronous.
AB  - The levator ani of the female adult rat is greatly atrophied in comparison to the
      same muscle in males. In the present study, the female levator ani was,
      nevertheless, found to contain type IIb myosin isoforms similar to those
      contained in the male muscle. These adult type isoforms were, however,
      synthesized later in the female than in the male levator ani: the half-transition
      times of the myosin transition curve were 20 days postnatal in the male and 35
      days postnatal in the female. The transition curves for castrated and uncastrated
      male rats were the same. Thus, the presence of male gonadal hormones apparently
      did not affect the myosin transition.

PMID- 1993474
TI  - Electrophysiological characterization of a new member of the RCK family of rat
      brain K+ channels.
AB  - A novel member of the RCK family of rat brain K+ channels, called RCK2, has been
      sequenced and expressed in Xenopus oocytes. The K+ currents were voltage
      dependent, activated within 20 ms (at 0 mV), did not inactivate in 5 s, and had a
      single channel conductance in frog Ringers of 8.2 pS. Compared to other members
      of the RCK family the pharmacological profile of RCK2 was unique in that the
      channel was resistant to block (IC50 = 3.3 microM) by charybdotoxin [(1988) Proc.
      Natl. Acad. Sci. USA 85, 3329-3333] but relatively sensitive to 4-aminopyridine
      (0.3 mM), tetraethylammonium (1.7 mM), alpha-dendrotoxin (25 nM), noxiustoxin
      (200 nM), and mast cell degranulating peptide (200 nM). Thus, RCK2 is a non
      inactivating delayed rectifier K+ channel with interesting pharmacological
      properties.

PMID- 1993475
TI  - Effect of removal of zinc on alfalfa mosaic virus RNA-dependent RNA polymerase.
AB  - The necessity of coat protein for infection of plants by alfalfa mosaic virus
      (AIMV) and other ilarviruses distinguishes this virus group from other plant
      virus groups. Recently, the presence of both a zinc-finger type motif and zinc in
      AIMV coat protein was described [(1989) Virology 168, 48-56]. We studied the
      effect of a zinc chelator on viral RNA synthesis. Strong inhibition of AIMV RNA
      dependent RNA polymerase (RdRp) by ortho-phenanthroline (OP) was observed.

PMID- 1993476
TI  - Cooperative B-Z transition of poly(dG-dC) induced by spermine at physiological
      temperature in aqueous medium.
AB  - Spermine induced B-Z transition of poly(dG-dC) in aqueous medium at and above
      physiological temperature, at cellular concentration levels in low ionic strength
      medium. The amine to phosphate ratio, A/P, at the midpoint of the transition
      decreases with increase in temperature. The enthalpy change was 45 +/- 8 kcal per
      mol of cooperative unit; the transition induced by spermine is highly cooperative
      with a cooperative unit length of 700 +/- 20 at 50 degrees C.

PMID- 1993477
TI  - Hemolytic activity of adenylate cyclase toxin from Bordetella pertussis.
AB  - Adenylate cyclase (AC) toxin from B. pertussis enters eukaryotic cells where it
      produces supraphysiologic levels of cAMP. Purification of AC toxin activity
      [(1989) J. Biol. Chem. 264, 19279] results in increasing potency of hemolytic
      activity and electroelution of the 216-kDa holotoxin yields a single protein with
      AC enzymatic, toxin and hemolytic activities. AC toxin and E. coli hemolysin,
      which have DNA sequence homology [(1988) EMBO J. 7, 3997] are immunologically
      cross-reactive. The time courses of hemolysis elicited by the two molecules are
      strikingly different, however, with AC toxin eliciting cAMP accumulation with
      rapid onset, but hemolysis with a lag of greater than or equal to 45 min.
      Finally, osmotic protection experiments indicate that the size of the putative
      pore produced by AC toxin is 3-5-fold smaller than that of E. coli hemolysin.

PMID- 1993478
TI  - A correlation between liver plasma membrane-associated stimulatory activity
      (PMASA) and experimental cirrhosis formation.
AB  - In the course of experimental CCl4-induced cirrhosis, an increase of the membrane
      associated factor stimulating 3T3 cells' proliferation in vitro was observed. Gel
      filtration showed an approximate molecular mass of 150 kDa. Extraction of growth
      stimulatory activity by liver perfusion in situ demonstrated a peripheral plasma
      membrane protein localization. The activity increased with an increasing number
      of CCl4 treatments, reaching a maximum at the tenth intoxication, faster than the
      proliferation of connective tissues. Cessation of treatment caused a decrease in
      activity to the level of untreated liver, although the amount of fibroblast-like
      cells remained large, which is evidence in favour of an hepatocyte origin of the
      factor.

PMID- 1993479
TI  - Gene organization of oryzacystatin-II, a new cystatin superfamily member of plant
      origin, is closely related to that of oryzacystatin-I but different from those of
      animal cystatins.
AB  - The gene structure of oryzacystatin-II, a new cystatin superfamily member of rice
      seed origin, was determined. It spans approximately 2.5 kbp and comprises 3
      exons. The number of exons and the intron-breakpoints coincide with those of
      oryzacystatin-I, the first well-defined plant cystatin. However, no similar
      sequences were observed between the two oryzacystatin genes in 5'-upstream
      regulatory regions, even though both are expressed specifically during the
      ripening stage of rice seeds. The gene organization of these two plant cystatins
      is generally different from that of animal cystatins.

PMID- 1993480
TI  - Solution conformation of endothelin, a potent vaso-constricting bicyclic peptide.
      A combined use of 1H NMR spectroscopy and distance geometry calculations.
AB  - The solution structure of endothelin-1, a newly discovered potent bicyclic
      peptide vaso-constrictor agent, has been investigated using 1H NMR conformational
      constraints and distance geometry calculations. The conformation is constrained
      by two disulphide bridges between Cys1-Cys15 and Cys3-Cys11 but the NMR data and
      computed conformers show additional helical structure between residues Leu6 and
      Cys11. Our results are compared with previous conflicting reports on the solution
      conformation of this peptide.

PMID- 1993481
TI  - Reduction of biological activity of murine recombinant interleukin-1 beta by
      selective deamidation at asparagine-149.
AB  - A biologically active preparation of murine recombinant interleukin-1 beta (mIL-1
      beta) from Escherichia coli cell lysates contained tow forms of mIL-1 beta with
      pI 8.7 and pI 8.1, respectively. Treatment with 0.1 M Tris, pH 8.5, at 37 degrees
      C for 35 h converted the pI 8.7 form to the pI 8.1 form by the selective
      deamidation of an asparagine residue (Asn149) in the mIL-1 beta molecule.
      Deamidated mIL-1 beta had 3- to 5-fold lower co-mitogenic activity and receptor
      affinity than the unmodified form.

PMID- 1993482
TI  - Gender differences in Manning criteria in the irritable bowel syndrome.
AB  - The objective of this study was to determine if gender differences exist when
      using the Manning criteria for diagnosis of irritable bowel syndrome. In an
      outpatient setting, 61 women and 36 men with entry complaints of abdominal pain,
      altered bowel habits, or both underwent full evaluation by board
      certified/eligible gastroenterologists who also systematically rated the presence
      or absence of the six Manning criteria. Irritable bowel syndrome was defined as
      the absence of an organic disease explanation for the entry complaints. This
      determination was made by two other board-certified gastroenterologists after
      patients had been in the study for 9 months. These raters were independent of the
      study and rated the transcripts of patients' clinic visits, all other available
      clinical data from this and other clinics, all laboratory data obtained during
      the 9-month study period, and the results of a 9-month telephone follow-up to
      patients and their physicians. Sixty-five percent of the study population had no
      organic disease explanation for the entry symptoms, thereby representing
      irritable bowel syndrome for this study. A similar proportion and type of organic
      disease and irritable bowel syndrome were experienced by men and women. For the
      total sample of 97 subjects, the correlation of the Manning criteria with
      irritable bowel syndrome was 0.22 (P less than 0.01). In the 61 women,
      correlation between the Manning criteria and irritable bowel syndrome was
      significant (r = 0.47; P less than 0.01). In the 36 men, however, the correlation
      was in the opposite direction, although it was not significant (r = -0.16). It
      was concluded that significant gender differences exist when using the Manning
      criteria for the diagnosis of irritable bowel syndrome and that the Manning
      criteria were not of diagnostic value in men.

PMID- 1993483
TI  - Impairment of esophageal emptying with hiatal hernia.
AB  - Concurrent videofluoroscopy and manometry were used to analyze esophageal
      emptying during barium swallows in 22 patients with axial hiatal hernias and in
      14 volunteers. Subjects were divided into three groups: (a) volunteers with
      maximal phrenic ampullary length less than 2 cm (controls); (b) patients or
      volunteers with maximal ampullary/hiatal hernia length greater than or equal to 2
      cm that reduced between swallows (reducing-hernia group); and (c) patients with
      hernias that did not reduce between swallows. Complete esophageal emptying
      without retrograde flow was achieved in 86% of test swallows in the controls, 66%
      in the reducing-hernia group, and 32% in the nonreducing-hernia group (P less
      than 0.05). Impaired emptying in the reducing-hernia group was attributable to
      "late retrograde flow," whereby barium squirted retrograde from the hernia during
      emptying. Impaired emptying in the nonreducing-hernia group was attributable to
      "early retrograde flow" that occurred immediately after LES relaxation. The
      nonreducing-hernia group also had longer acid clearance times than the controls
      (P less than 0.05). We conclude that gastroesophageal junction competence is
      severely impaired in patients with nonreducing hiatal hernias, suggesting a
      mechanism whereby this subgroup of hiatal hernia is involved in the pathogenesis
      of reflux disease.

PMID- 1993484
TI  - Role of leukotriene C4 in mucosal damage caused by necrotizing agents and
      indomethacin in the rat stomach.
AB  - Intragastric ethanol stimulates mucosal formation of leukotriene C4 in the rat
      stomach. The present study demonstrates that the increase in leukotriene C4
      formation begins within 30 seconds and is maximal within 5 minutes, closely
      paralleled by the appearance of hemorrhagic lesions. Leukotriene C4 formation
      returns to prechallenge levels within 3 hours, although erosions still persist.
      Intragastric 0.2N NaOH, acidified 100 mmol/L taurocholate, 25% NaCl, or 0.6N HCl
      did not consistently increase leukotriene C4 formation despite severe mucosal
      injury. A number of sulfhydryl-containing or sulfhydryl-blocking agents as well
      as metals protected against mucosal damage and simultaneously prevented the
      stimulation of leukotriene C4 formation induced by ethanol. None of the agents
      increased and some virtually abolished mucosal formation of prostaglandin E2,
      indicating that gastroprotection can occur completely independently of the
      endogenous prostaglandin system. The leukotriene biosynthesis inhibitor MK-886
      markedly suppressed gastric leukotriene C4 formation but did not protect against
      damage caused by ethanol, NaOH, NaCl, or acidified taurocholate. Oral
      indomethacin reduced the ex vivo formation of both prostaglandin E2 and, to a
      lesser extent, leukotriene C4 in the gastric mucosa, inducing a shift in the
      balance from protective prostaglandins to proulcerogenic leukotriene C4.
      Pretreatment with MK-886, however, did not significantly diminish indomethacin
      induced lesions. These data suggest that leukotriene C4 is not the exclusive
      mediator of gastric injury caused by necrotizing agents or indomethacin. On the
      other hand, certain protective compounds exhibit a striking parallelism between
      protection and inhibition of ethanol-induced leukotriene C4 formation, suggesting
      that they may affect a target crucial for both mucosal injury and stimulation of
      5-lipoxygenase.

PMID- 1993485
TI  - Abdominal pathways and central origin of rat vagal fibers that stimulate gastric
      acid.
AB  - The brainstem location and peripheral course of the vagal preganglionic fibers
      that stimulate gastric acid secretion were identified using electrical
      stimulation combined with retrograde (True Blue; Dr. K. G. Illing, Gross Umstadt,
      Germany) and anterograde (Dil; Molecular Probes) fluorescent neural tracers in
      rats with various selective vagotomies. Animals with only one or both gastric
      branch(es) spared had normal, large gastric acid responses to electrical
      stimulation of the ipsilateral cervical vagus and showed an abundance of Dil
      labeled vagal fibers and terminals in the gastric myenteric plexus. Rats with
      only the unpaired hepatic branch spared had a much smaller but significant
      gastric acid response and a few labeled vagal profiles in the antral region of
      the stomach. In contrast, rats with only one or both celiac branch(es) intact had
      neither a gastric acid response, nor evidence for Dil transport to the stomach.
      Retrograde transport of True Blue through the spared vagal axons to the brainstem
      indicated that the cell bodies of the preganglionics that send their axons
      through the acid-positive gastric and hepatic branches occupy the medial
      longitudinal columnar subnuclei of the dorsal motor nucleus. It is concluded that
      besides the long-recognized gastric branches, which are the major access route to
      the parietal cells, the hepatic branch contains a small number of fibers that
      most likely reach the antrum through the right gastroepiploic artery along the
      greater curvature and/or the right gastric artery.

PMID- 1993486
TI  - The microvascular anatomy of the canine stomach. A comparison between the body
      and the antrum.
AB  - To investigate whether there is a difference in the microvascular architecture
      between the body and the antrum of the canine stomach, these two locations were
      compared with respect to microsphere entrapment and the microvascular
      architecture and diameter in relation to histology by corrosion casting and by
      intraarterial injection of india ink. There was 63% shunting of 9-micron
      microspheres in the antrum, but none in the body. Corrosion cast and Indian ink
      studies showed that in the body there was a single microvascular network of
      capillaries that appeared to originate from the arterioles in the submucosa and
      were in close apposition to the epithelial cells of the gastric glands. The
      diameter of these capillaries was 8.6 +/- 0.2 microns. In contrast, there were
      two distinct capillary networks in the antrum: a basal and a superficial. The
      capillaries of the basal network of the antrum originated from the arterioles at
      the level of the muscularis mucosa and drained into the capillaries of the
      superficial mucosa. The capillaries of the superficial network had a
      significantly larger diameter (10.8 +/- 0.4 microns) than those of the basal
      network (7.3 +/- 0.2 microns). In many instances the capillaries of the
      superficial network originated directly from the ascending arterioles passing
      through the basal network. These direct arteriocapillary connections may have
      permitted the shunting of 9-microns spheres in the antrum.

PMID- 1993487
TI  - Acid-induced increase in electrical conductance of guinea pig duodenal mucosa in
      vitro. Temporary protection by combined effects of bicarbonate and prostaglandin
      E2.
AB  - Electrical conductance as a sensitive indicator of acid damage has been
      investigated in guinea pig duodenal mucosa using Ussing-chamber techniques.
      Reductions of luminal pH from 7.4 to 3.0, 2.3, or 2.0 caused concentration
      dependent, progressive increases in conductance, accompanied (pH 2.0) by a
      continuous increase in hydrogen permeation as determined by pH-stat titration.
      Increases in conductance and hydrogen flux were related to base-line conductance,
      with higher values conditioning for a sooner onset and/or more marked elevation.
      Conductance increases were prevented by timely back titration. Recently, it has
      been shown that serosal HCO3 reduces conductance by actions dependent on
      prostaglandins and serosal Na and sensitive to loop diuretics. Here, serosal HCO3
      delayed the onset of acid-induced conductance increase by approximately 8
      minutes, an effect reduced by omission of serosal Na and during exposure to
      serosal furosemide (10(-3) mol/L). In the presence of serosal indomethacin (10(
      4) mol/L) and HCO3, prostaglandin E2 (10(-6) mol/L serosal bath) delayed the
      conductance increase. Because HCO3 secretion is negligible in this model, these
      results indicate effects of HCO3/prostaglandin E2 beyond mere buffering of
      invading hydrogen. These results are consistent with intracellular actions that
      tighten the paracellular pathway against acid and thus provide temporary
      protection from acid injury. In agreement with this view, HCO3 also limited
      conductance increases after luminal alkalinization by a furosemide-sensitive
      action.

PMID- 1993488
TI  - Omeprazole 20 mg three days a week and 10 mg daily in prevention of duodenal
      ulcer relapse. Double-blind comparative trial.
AB  - In a double-blind, parallel-group clinical trial of 195 patients with duodenal
      ulcers who after a short-term study had relief of pain and healed ulcers proved
      endoscopically, 65 were randomized to receive 20 mg omeprazole 3 days a week
      (once in the morning from Friday to Sunday), 64 to receive 10 mg omeprazole once
      daily in the morning, and 66 to receive placebo for up to 6 months. The patients
      underwent repeat endoscopy with biopsy of the gastric fundic mucosa (qualitative
      assessment of argyrophilic cell population), assessment of symptoms, and
      laboratory screening with measurement of basal serum gastrin concentrations at 3
      and 6 months or more often if indicated by recurrence of symptoms. At 3 months,
      endoscopically proved ulcer relapse occurred in 16% receiving 20 mg omeprazole 3
      days a week; 21% receiving 10 mg omeprazole daily; and 50% receiving placebo. At
      6 months, corresponding rates were 23%, 27%, and 67% with 95% confidence
      intervals of difference between the placebo group and omeprazole groups of 28%
      60% and 24%-56% (P less than 0.00001), respectively, and between omeprazole
      groups of -19%-11% (NS). No major clinical or laboratory side effects were noted.
      Thus both omeprazole regimens are effective and safe in preventing duodenal ulcer
      relapse.

PMID- 1993489
TI  - Small intestinal transit in the portal hypertensive rat.
AB  - The purpose of this study was to determine the effects of portal hypertension on
      gastrointestinal transit. Portal hypertension was induced in a group of 15 rats
      by the staged portal vein ligation technique. A control group of 15 rats
      underwent a sham operation. Ten days later, a 51Cr-labeled Krebs' buffer solution
      was instilled into the duodenum and the distribution or radioactivity along the
      length of the small intestine was determined after 15, 30, and 60 minutes. Portal
      hypertension was consistently established in the study group; splenic pulp
      pressure (mm Hg, mean +/- SD, portal hypertensive vs. control) was 20.0 +/- 3.9
      vs. 12.7 +/- 3.9, P less than 0.002. Various measures of intestinal transit
      revealed delayed transit in the portal hypertensive group. Retention of
      radioactivity in the most proximal quartile of the intestine was greater
      [percentage retained (portal hypertensive vs. control) was 57.9 +/- 17.3 vs. 31.2
      +/- 15.3, P less than 0.02, 49.1 +/- 15.5 vs. 28.3 +/- 4.8, P = 0.03, and 42.4 +/
      17.6 vs. 29.0 +/- 8.8, P = 0.08, at 15, 30, and 60 minutes, respectively] and
      the geometric mean of transit was located more proximally (P less than 0.02) at
      each study interval in the portal hypertension group. It was concluded that
      portal hypertension is associated with delayed intestinal transit. This
      abnormality could predispose to bacterial overgrowth and contribute to altered
      digestion and absorption.

PMID- 1993490
TI  - Isolation and characterization of normal and neoplastic colonic epithelial cell
      populations.
AB  - The aim of the present study was to characterize rat mucosal colonic cells
      harvested from the crypt continuum during differentiation and dimethylhydrazine
      induced neoplasia. The collection of colonocytes was performed using a modified
      nonenzymatic isolation procedure based on Ca2+ chelation and gentle mechanical
      dissociation. Light and electron microscopy histomorphological examinations,
      [3H]thymidine incorporation studies, and activity gradients of alkaline
      phosphatase, thymidine kinase, and cytoskeleton-associated protein tyrosine
      kinase indicated that distinct cell populations were harvested from the various
      crypt regions in a temporal sequence mirroring their zonal and functional
      distribution in situ. After dimethylhydrazine administration, marked protein
      tyrosine kinase activity was noted in colonic cells harvested from upper crypt
      zones. The misplaced and sustained kinase activity preceded the actual polyp or
      tumor formation. This observation is consistent with the expansion of colonic
      proliferative compartments beyond allowable boundaries during the preneoplastic
      period. Companion studies in human colonic epithelial specimens corroborate the
      findings observed in normal and transformed murine colonocytes. It is believed
      that the characterization and manipulation of colonocytes using our in vitro
      model will provide important clues to the molecular events underlying the
      differentiation program and carcinogenic process in the colonic cell.

PMID- 1993491
TI  - Regulation of ion transport in porcine distal colon: effects of putative
      neurotransmitters.
AB  - Porcine distal colon epithelium was mounted in Ussing chambers and bathed with
      porcine Ringer's solution. The effects of vasoactive intestinal polypeptide,
      norepinephrine, and carbamylcholine on Na and Cl fluxes and transepithelial
      electrical parameters were determined after their serosal administration.
      Vasoactive intestinal peptide increased the Cl-dependent component of the short
      circuit current with a half-maximal effect at 115 nmol/L. Transepithelial Na and
      Cl flux studies demonstrated that the increase in current was caused by
      stimulation of Cl secretion. Norepinephrine also stimulated Cl secretion and
      increased the serosal-to-mucosal Na flux, producing a half-maximal effect at 1.6
      mumol/L. Selective blockade of alpha 1 adrenoceptors by 0.5 mumol/L prazosin
      produced an eightfold decrease in norepinephrine potency. Carbamylcholine
      produced a significant increase in Cl secretion and decreased absorption of both
      Na and Cl with a concentration of 10 mumol/L producing a half-maximal effect. The
      muscarinic cholinoceptor blocker atropine (0.1 mumol/L) produced a 22-fold
      decrease in carbamylcholine potency. The effects of all three transmitter
      substances were unaffected after pretreatment of tissues with the neuronal
      conduction-blocker tetrodotoxin or an inhibitor of arachidonic acid metabolism.
      These results indicate that (a) vasoactive intestinal polypeptide stimulates Cl
      secretion without affecting Na absorption; (b) norepinephrine acting through
      alpha 1 adrenoceptors stimulates net Cl secretion and activates a serosal-to
      mucosal Na transport mechanism; and (c) carbamylcholine acting through muscarinic
      receptors stimulates Cl secretion and inhibits Na and Cl absorption.

PMID- 1993492
TI  - An oligopeptide permeates intestinal tight junctions at glucose-elicited
      dilatations. Implications for oligopeptide absorption.
AB  - Turnover of the Na(+)-glucose cotransporter in the apical membrane of intestinal
      absorptive cells elicits alterations in tight-junction structure including the
      appearance of intrajunctional dilatations. Paralleling these structural
      responses, epithelial permeability to ions and nutrient-sized solutes increases.
      However, it is not known how these observed permeability changes specifically
      relate to the structural alterations elicited by glucose. Using a hemeconjugated
      peptide tracer (MP-11; mol wt, approximately 1900), the present study shows that
      the glucose-elicited tight-junction dilatations are specific anatomical sites of
      junctional permeation. This peptide tracer penetrates tight junctions selectively
      at sites of dilatations and is detected focally within the paracellular space.
      This same tracer does not penetrate junctions when glucose is not present. A heme
      conjugated macromolecule (horseradish peroxidase; mol wt, approximately 40,000)
      is excluded by both glucose-exposed and glucose-unexposed tissues. The results of
      this study show a paracellular pathway for small peptides that is regulated
      during Na(+)-glucose-activated absorption. It is speculated that the paracellular
      pathway may contribute to the meal-related oligopeptide absorption that is known
      to occur and has previously been wholly attributed to the transcellular route.

PMID- 1993493
TI  - Increased uptake of bromodeoxyuridine by hepatocytes from early stage of primary
      biliary cirrhosis.
AB  - The relationship between DNA synthesis activities of hepatocytes in biopsied
      specimens and liver volume was studied in various stages of primary biliary
      cirrhosis using an in vitro bromodeoxyuridine (a thymidine analogue)-anti
      bromodeoxyuridine reaction and computed tomography. The mean bromodeoxyuridine
      (+/- SE) labeling index for 10 patients in an early histological stage (stage I,
      4, and stage II, 6, 3.4% +/- 0.4%) of primary biliary cirrhosis was 17 times that
      for 6 control subjects (0.2% +/- 0.1%, P less than 0.001), and was significantly
      higher than that for 19 female patients with chronic aggressive hepatitis (0.9%
      +/- 0.2%, P less than 0.001), 14 compensated cirrhotic patients of viral origin
      (all female, 1.1% +/- 0.3%, P less than 0.01), and 5 patients with stage III
      primary biliary cirrhosis (0.5% +/- 0.1%, P less than 0.001). The mean (+/- SE)
      liver volume in the early stage of primary biliary cirrhosis (1225 +/- 40 cm3)
      was about 1.5 times that in control subjects (835 +/- 42 cm3, P less than 0.001).
      These results suggest that liver volume has already become large in the early
      stage of primary biliary cirrhosis perhaps because of markedly increased DNA
      synthesis in hepatocytes.

PMID- 1993494
TI  - Glucose and fat metabolism during short-term starvation in cirrhosis.
AB  - To evaluate the metabolic consequences of short-term (i.e., less than 24 hours)
      starvation, glucose and fat metabolism were studied in eight healthy subjects and
      in eight patients with stable cirrhosis after 16-hour and again after 22-hour
      starvation by 3-[3H]glucose and [14C]palmitate turnover and by indirect
      calorimetry. Although patients and controls showed significant increases in free
      fatty acid concentration (respectively, 48% +/- 12% and 53% +/- 17%) and turnover
      (55% +/- 14% and 71% +/- 21%) during short-term starvation, the values after 16-
      and after 22-hour starvation were higher in cirrhosis. Fat oxidation was enhanced
      in the patients, but did not increase during fasting in contrast to controls
      (increase 19% +/- 17%, P less than 0.05). Net glucose oxidation was decreased in
      postabsorptive cirrhotics (P less than 0.05). Although postabsorptive glucose
      turnover was not different from controls, starvation induced a greater decrease
      in glucose turnover in the patients (25% +/- 3% vs. 10% +/- 3%, P less than
      0.05). This was not reflected in plasma glucose concentrations. In conclusion,
      the effects of starvation on glucose and fat metabolism are enhanced in
      cirrhosis; fasting hypoglycemia is prevented by decreased use of glucose. It
      remains to be established whether these changes are merely explained by defective
      liver function, per se.

PMID- 1993495
TI  - Ascites increases the resting energy expenditure in liver cirrhosis.
AB  - The purpose of this study was to investigate the effect of ascites on the energy
      metabolism of patients with liver cirrhosis. The resting energy expenditure was
      determined in 10 patients with liver cirrhosis and ascites of moderate or large
      volume. The resting energy expenditure measurement was performed using indirect
      calorimetry and the resting energy expenditure predictive value was calculated
      with the Harris-Benedict equation, both before and after removal of ascitic fluid
      by paracentesis. Metabolic stress factors were absent in all cases. After an
      interval of 11.2 +/- 7.7 days between measurements, a weight loss of 16.6 +/-
      10.3 kg was observed with paracentesis. The resting energy expenditure measured
      by indirect calorimetry showed a statistically significant decrease from 1682 +/-
      291 to 1523 +/- 240 kcal/day (P less than 0.005) after removal of ascites. The
      repeatability of our indirect calorimetry method only allowed for the analysis of
      the results in 4 of 10 patients in whom ascites removal produced a consistent
      decrease in resting energy expenditure. There were no statistically significant
      differences between the measurements obtained by indirect calorimetry and those
      provided by the Harris-Benedict equation, but the latter had a moderate
      reliability in predicting the real resting energy expenditure of every patient.
      Our results suggest that, far from being an inert volume, ascites may be
      associated, at least in some patients, with an increased resting energy
      expenditure and therefore accelerate the appearance of protein energy
      malnutrition with corresponding complications.

PMID- 1993496
TI  - High-protein ascites in patients with the acquired immunodeficiency syndrome.
AB  - Diseases of the liver or peritoneum resulting in ascites have been infrequently
      reported in patients with the acquired immunodeficiency syndrome. Since 1985,
      eight noncirrhotic patients with the acquired immunodeficiency syndrome
      presenting with new onset high-protein ascites have been evaluated. All but one
      patient had nondiagnostic paracentesis studies. Laparoscopy with biopsy of
      identified abnormalities or percutaneous omental biopsy were diagnostic in four
      patients. Non-Hodgkin's lymphoma was the cause in three patients, and
      disseminated cryptococcosis occurred in one patient. In the four other patients,
      chronic nonspecific peritonitis was found at laparoscopy; follow-up of these
      latter patients, including exploratory laparotomy in one patient and autopsy in
      two patients, disclosed no specific cause. Patients with the acquired
      immunodeficiency syndrome and high-protein ascites of uncertain etiology should
      undergo directed peritoneal evaluation as a potentially treatable disorder may be
      found. However, despite extensive evaluation, a subset of patients in whom no
      specific cause can be identified still remains.

PMID- 1993497
TI  - Interferon alfa therapy in patients with chronic hepatitis B virus infection.
      Effects on hepatitis B virus DNA in the liver.
AB  - Pretrial and posttrial liver biopsy samples from 124 adult patients who
      participated in two randomized, controlled trials of interferon alfa therapy for
      chronic hepatitis B virus (HBV) infection were analyzed to determine the effects
      of interferon on the replication of HBV in the liver. Replicative forms of HBV
      DNA were detected in the pretrial biopsy samples from all and posttrial biopsy
      samples from 74% treated patients and 86% controls. Replicative forms of HBV DNA
      were detected in the posttrial biopsy samples from all patients who remained
      positive for hepatitis B e antigen and HBV DNA in the serum, in 77% treated
      patients and 80% controls who cleared HBV DNA in the serum but who remained
      positive for hepatitis B e antigen, but in only 19% treated patients and 40%
      controls who cleared HBV DNA as well as hepatitis B e antigen in the serum. Serum
      alanine aminotransferase levels were significantly lower in patients whose
      posttrial biopsies did not contain replicative forms of HBV DNA. In summary, we
      demonstrated that in most patients with chronic HBV infection treated with
      interferon alfa, serological response was associated with the disappearance of
      replicative forms of HBV DNA in the liver.

PMID- 1993498
TI  - Prognosis of Wilsonian chronic active hepatitis.
AB  - Twenty of 320 patients with Wilson's disease initially presented with chemical
      and laboratory features of chronic active hepatitis, confirmed histologically in
      17. When first seen, cirrhosis was present in all 20 and was complicated by
      ascites and/or jaundice in 11. Within 1 week to 8 years of the onset of over
      liver disease the diagnosis of Wilson's disease was established, and treatment
      with D-penicillamine was promptly initiated in 19 patients. One man refused
      treatment and died 4 months later. Treated patients received D-penicillamine or
      trientine for a total of 264 patient-years (median, 14 patient-years). Abnormal
      water retention, for which salt restriction and diuretics were added to
      penicillamine or trientine, disappeared in all but 1 of the patients so affected.
      Symptomatic improvement and virtually normal levels of serum albumin, bilirubin,
      aspartate aminotransferase, and alanine aminotransferase followed within 1 year
      in the majority of subjects. One woman died after 9 months of treatment. Two
      patients, who became noncompliant with the therapeutic regimen after 9 and 17
      years of successful pharmacological treatment, required liver transplants. These
      results indicate that the prognosis of specifically treated Wilsonian chronic
      active hepatitis is very good in spite of the presence of cirrhosis.

PMID- 1993499
TI  - Studies on the sterol-binding capacity of human pancreatic elastase 1.
AB  - In previous studies we isolated human pancreatic elastase 1 from intestinal
      lavage fluids, where it was found to be part of a complex whose major component
      was cholesterol. The present study involves the isolation and characterization of
      this elastase 1-sterol complex recovered from feces of healthy subjects and
      patients whose intestinal microflora were nearly eradicated by antibiotics.
      Results indicate that elastase 1 essentially is complexed with neutral sterols,
      i.e., cholesterol, coprostanol, and coprostanone, in a weight ratio of about
      1:1.5, corresponding to about 110 molecules of neutral sterols per one elastase 1
      molecule. This complex is elutable with water from the solid moiety of the
      stools. Elastase 1 thus seems to fulfill the important function of maintaining
      water solubility of neutral sterols at low bile acid concentrations.

PMID- 1993500
TI  - The differential diagnosis of Crigler-Najjar disease, types 1 and 2, by bile
      pigment analysis.
AB  - Phenobarbital response, bile pigment composition, and the fractional biliary
      excretion ratio of bilirubin were studied in nine children with Crigler-Najjar
      disease. In five children, serum bilirubin levels decreased during phenobarbital
      treatment by 26% or more and the pigment composition in bile changed with a
      decrease in the proportion of unconjugated bilirubin from 33% +/- 12% to 13% +/-
      1% and an increase in monoconjugates and diconjugates from 57% +/- 14% and 10% +/
      2%, respectively, to 72% +/- 4% and 16% +/- 3%. In four children, serum
      bilirubin levels did not change significantly during phenobarbital treatment. In
      these patients, bile pigments comprised 91% +/- 10% unconjugated bilirubin, 9% +/
      11% monoconjugates, and 1% +/- 1% diconjugates. On the basis of these
      differences, the former group can be classified as having type 2 Crigler-Najjar
      disease and the latter, type 1. Bile pigment analysis in parents of patients with
      Crigler-Najjar disease showed an increased proportion of monoconjugates in at
      least one of the partners in three of four couples tested, despite normal serum
      bilirubin levels. Serum bilirubin levels were about the same in type 1 and 2
      patients and amounted to 236 +/- 62 mumol/L and 214 +/- 82 mumol/L, respectively.
      In addition the fractional bilirubin excretion ratio, calculated as the ratio
      ([bilirubin in bile]/[bilirubin in serum])/([bile acid in bile]/[bile acid in
      serum]) could not differentiate between these two groups. However, there was a 10
      fold and 100-fold difference of this ratio between patients with Crigler-Najjar
      disease and those with Gilbert's syndrome and between patients with Crigler
      Najjar disease and controls. The fractional bilirubin excretion ratio proved an
      excellent tool to differentiate between Gilbert's syndrome and Crigler-Najjar
      disease, whereas Crigler-Najjar disease types 1 and 2 could be differentiated on
      the basis of bile pigment analysis.

PMID- 1993501
TI  - Incidence of gallstones in a Danish population.
AB  - Five-year incidence of gallstone disease was assessed by ultrasonography in an
      age- and sex-stratified random population of Danish origin aged 30, 40, 50, and
      60 years. The response rate was 82.8% (2987/3608). Nonrespondents did not differ
      from respondents regarding variables concerning gallstone disease. The 5-year
      incidence of gallstone disease in men aged 30, 40, 50, and 60 years was 0.3%,
      2.9%, 2.5%, and 3.3%. Corresponding figures in women were 1.4%, 3.6%, 3.1%, and
      3.7%. The incidence of gallstones was significantly higher in subjects aged 45
      years or more compared with those aged 35 years. The sex difference in gallstone
      incidence decreased with increasing age. A significantly higher incidence of
      gallstone disease was found among subjects with former polyps in the gallbladder.
      Spontaneous disappearance of gallstones was seen in 4.5%.

PMID- 1993502
TI  - Ampullary hamartoma: endoscopic diagnosis and treatment.
AB  - This study shows a patient who presented with intermittent biliary tract
      obstruction caused by ampullary hamartoma. Endoscopic retrograde
      cholangiopancreatography showed a large ulcerated papilla and dilated biliary
      ducts. Tissue diagnosis was established by a large particle biopsy obtained with
      a snare. The patient underwent a successful endoscopic sphincterotomy and has
      remained symptom free for 4 years.

PMID- 1993503
TI  - The role of continued drinking in loss of portal perfusion after distal
      splenorenal shunt.
AB  - Fifty percent of patients with alcoholic cirrhosis who undergo distal splenorenal
      shunting for variceal bleeding lose portal perfusion within 1 year. Although it
      was previously considered that this loss of portal flow was irrevocable, the
      present study shows that with resolution of alcoholic hepatitis, portal perfusion
      can be restored. A 34-year-old patient with alcoholic liver disease and a distal
      splenorenal shunt lost portal perfusion 1 year after the operation. He had
      continued to drink alcohol and had high sinusoidal pressure. Following forced
      abstinence over the next 2 years, his sinusoidal pressure fell, liver volume
      decreased, results of liver biopsy improved, and portal perfusion was restored.
      Shunt patency was documented, and the same collaterals from the portal vein to
      the shunt could still be visualized as had been seen when portal flow was absent.
      Restoration of portal perfusion was attributed to decreased intrahepatic
      resistance secondary to abstinence from alcohol. A return to drinking in the next
      9 months led to alcoholic hepatitis and once again loss of portal perfusion. This
      study places emphasis on increased intrahepatic resistance rather than the
      development of portal-to-shunt collaterals as important in the loss of portal
      flow in such patients.

PMID- 1993504
TI  - Hereditary internal anal sphincter myopathy causing proctalgia fugax and
      constipation. A newly identified condition.
AB  - A newly identified myopathy of the internal anal sphincter is described. In the
      affected family, at least one member from each of five generations had severe
      proctalgia fugax; onset was usually in the third to fifth decades of life. Three
      members of the family have been studied in detail. Each had severe pain
      intermittently during the day and hourly during the night. Constipation was an
      associated symptom, in particular difficulty with rectal evacuation. Clinically
      the internal anal sphincter was thickened and of decreased compliance. The
      maximum anal canal pressure was usually increased with marked ultraslow wave
      activity. Anal endosonography confirmed a grossly thickened internal anal
      sphincter. Two patients were treated by internal anal sphincter strip myectomy;
      one showed marked improvement and one was relieved of the constipation but had
      only slight improvement of the pain. The hypertrophied muscle in two of the
      patients showed unique myopathic changes, consisting of vacuolar changes with
      periodic acid-Schiff-positive polyglycosan bodies in the smooth muscle fibers and
      increased endomysial fibrosis. In vitro organ-bath studies showed insensitivity
      of the muscle to noradrenaline, isoprenaline, carbachol, dimethylpiperazinium,
      and electrical-field stimulation. Immunohistochemical studies for substance P,
      calcitonin gene-related peptide, galanin, neuropeptide Y, and vasoactive
      intestinal peptide showed staining in a similar distribution to that in control
      tissue. A specific autosomal-dominant inherited myopathy of the internal anal
      sphincter that causes anal pain and constipation has been identified and
      characterized.

PMID- 1993505
TI  - Microvillus inclusion disease. In vitro jejunal electrolyte transport.
AB  - Microvillus inclusion disease is an inherited intestinal brush border membrane
      defect that causes severe fluid and electrolyte malabsorption. In an infant with
      microvillus inclusion disease (confirmed by electron microscopic evaluation of
      rectal, jejunal, and gallbladder mucosae), basal stool output was massive
      (greater than 125 mL . kg-1 . day-1) and was not altered by treatment with
      clonidine or octreotide. A proximal jejunostomy with mucous fistula was placed,
      allowing separation of proximal from distal tract outputs (60 mL . kg-1 . day-1
      and 100 mL . kg-1 . day-1, respectively). A 10-cm jejunal segment was excised
      during surgery and mounted in Ussing chambers for determination of
      transepithelial Na+ and Cl fluxes. Compared with intestine of normal infants,
      this infant's epithelium showed transmural conductance and unidirectional ion
      fluxes that were only 30% of normal. With respect to both Na+ and Cl, the excised
      jejunum was in a net secretory state. Theophylline (5 mmol/L) increased net Cl
      secretion slightly. In response to mucosal D-glucose (30 mmol/L), jejunal mucosal
      to-serosal Na+ flux doubled. In the infant, glucose-electrolyte solution
      administered intrajejunally did not significantly change stool output, suggesting
      that all of the solution (40 mL/kg) was absorbed. Subtotal enterocolectomy, in
      theory, could have decreased purging by 66% in this infant with microvillus
      inclusion disease, but diarrhea would still have been significant.

PMID- 1993506
TI  - Extrahepatic portal vein aneurysm associated with a tortuous portal vein.
AB  - Portal vein aneurysm is rare and its etiology is controversial. A case of
      extrahepatic portal vein aneurysm associated with an unusually tortuous portal
      vein is described. Real-time ultrasonography showed anechoic masslike lesions at
      the porta hepatis communicating with the superior mesenteric vein and
      intrahepatic portal branches. This suggested the presence of two saccular portal
      vein aneurysms, 27 x 21 mm and 21 x 13 mm in size. Magnetic resonance imaging and
      portal venography confirmed the portal vein aneurysms and an unusually tortuous
      portal vein curving caudally between them. The liver was histologically normal
      and there was no evidence of portal hypertension. It is speculated that these
      portal vein aneurysms may have been congenital and that the associated tortuous
      portal vein might have been secondary to hemodynamic changes in the portal venous
      system.

PMID- 1993507
TI  - Primary biliary cirrhosis: paradigm or paradox for autoimmunity.
AB  - Primary biliary cirrhosis has been classified as a model autoimmune disease based
      on striking defects in immune regulation and the presence of autoantibodies to
      mitochondria. Until recently the significance and definition of mitochondrial
      autoreactivity was unknown. Since 1987, there has been a vast improvement in the
      understanding and definition of the biochemical and molecular target
      autoantigens. The cloning of complementary DNAs for mitochondrial antigens has
      led to the identification of three enzymes of the 2-oxo-acid dehydrogenase family
      as the targets of the autoantibodies to mitochondria in patients with primary
      biliary cirrhosis. The major reactive autoantigen is the E2 subunit of pyruvate
      dehydrogenase. Immunodominant sites on pyruvate dehydrogenase E2 (autoepitopes)
      have been mapped and have been shown to be the site of attachment of the
      functionally important lipoic acid prosthetic group. The autoepitope for the
      other enzymes probably occupies an equivalent site on the enzyme. The
      availability and definition of these mitochondrial autoepitopes have allowed
      specific questions to be addressed relating to the processing and targeting of
      these autoantigens as well as further studies on mechanisms of immunopathology.
      Similarly, the availability of well-defined autoantigens could contribute to the
      development of valid animal models in addition to the already described
      reproduction of the biliary ductular lesions by transfer of peripheral blood
      lymphocytes from patients with primary biliary cirrhosis into severe combined
      immunodeficient mice. Such models will facilitate specific study of the role of
      major histocompatibility complex expression and the characterization of T-cell
      reactivity. Thus, primary biliary cirrhosis is a key example of significant
      progress in autoimmunity being made by use of recombinant DNA technology.

PMID- 1993508
TI  - Diagnosing an irritable bowel: does sex matter?

PMID- 1993509
TI  - Enteroscopy: exploring the final frontier.

PMID- 1993510
TI  - Cystic fibrosis: another use for urso?

PMID- 1993511
TI  - Colon cancer and the p53 oncogene.

PMID- 1993512
TI  - Cholecystokinin-induced contractions in the opossum gallbladder.

PMID- 1993513
TI  - Intragastric balloons in obesity.

PMID- 1993514
TI  - Consultation liaison psychiatry as a subspecialty.

PMID- 1993515
TI  - A biopsychosocial treatment approach to the management of diabetes mellitus.
AB  - The relationship among recent life stress, social support, a patient's locus of
      control, and the control of blood glucose is evaluated in persons with diabetes
      mellitus, using objective measures of these psychosocial variables. Short-term
      [fasting blood sugar (FBS)] and long-term [glycosylated hemoglobin (Hgb A-1C)]
      control measures are taken at two points in time in order to evaluate the effects
      of the psychosocial variables on change in diabetes control. For life events, a
      significant positive association was found between the number of recent life
      events and blood glucose control. Decrease in social support predicted a
      worsening of longer-term (Hgb A-1C) control over time. An external locus of
      control within the patient was associated both with poor short-term control at
      time one and prediction of poorer long-term control over time. The implications
      of these findings are discussed in support of a biopsychosocial approach to the
      management of diabetes mellitus.

PMID- 1993516
TI  - Psychogenic abdominal pain.
AB  - A series of 25 patients referred for psychiatric consultation with nonspecific
      abdominal pain (NSAP) are compared with a prospectively admitted series who were
      not referred. The referred patients had a longer duration of pain and also had
      high levels of psychiatric illness. The referred patients had more life events
      associated with the onset of their pain than controls. Inquiry about previous
      psychiatric history, childhood abuse, and a symptom model would increase the
      detection of NSAP patients who require psychiatric evaluation. Outcome after
      recommended treatment is also addressed.

PMID- 1993517
TI  - Management of patient-staff and intrastaff problems in psychiatric consultations.
AB  - Four possible types of management of patient-staff and/or intrastaff (PS/IS)
      problems in psychiatric consultations are distinguished and operationalized. The
      occurrence and correlates of these types of interventions were studied in a
      multisite investigation of 1112 consecutive consultations in five general
      hospitals. PS/IS problems (possibly, probably, or certainly) played a role in
      28.1% of the consultations studied. The psychiatric consultants utilized a
      primarily patient-oriented approach in 56.7% of these 310 consultations, whereas
      in 42.3% they performed (covert or overt) staff-oriented case consultations. A
      staff-oriented approach may be contraindicated when the PS/IS problems are not
      very serious or too complex. In the literature staff resistance and hospital
      culture are frequently mentioned as obstacles to staff-oriented interventions.
      The present study showed, however, that it was often the consultants' own degree
      of security about the PS/IS problems that determined the way they handled these
      problems. Staff-oriented consultations took significantly more of the psychiatric
      consultants' time. The clinical and economic benefits of such interventions have
      still to be established. But the psychiatric consultant with a true
      biopsychosocial approach should always be cognizant of the possible occurrence of
      PS/IS problems and consider applying a staff-oriented intervention.

PMID- 1993518
TI  - Depressed patients who do and do not receive psychiatric consultation in general
      hospitals.
AB  - A chart review was conducted of depressed patients at three general hospitals
      without psychiatric units. A substantial proportion of the patients did not
      receive psychiatric consultation. These patients tended to be less seriously ill
      than those who were evaluated by consulting psychiatrists. Despite the fact that
      a majority of patients treated without consultation reported disturbances of
      mood, appetite, and sleep, as well as somatic pain for which no source was
      readily apparent, only a small proportion received antidepressants in standard
      dosages. Issues surrounding the indications for and attitudinal barriers to
      antidepressant use in primary care are discussed.

PMID- 1993519
TI  - Drug abuse and psychiatric findings in HIV-seropositive pregnant patients.
AB  - In a sample of 55 human immunodeficiency virus (HIV)-seropositive pregnant
      patients, a history of drug abuse was significantly associated with increased
      psychopathology, particularly depression and personality disorders. Psychiatric
      disorders preceded the HIV diagnosis in most of the patients studied. Intravenous
      drug abuse was also associated with increased prostitution, incarceration, and
      previous suicide attempts. Psychiatric findings were influenced much less by the
      HIV diagnosis and much more by the presence or absence of a history of drug
      abuse.

PMID- 1993520
TI  - Suicidal behavior among inner-city Hispanic adolescent females.
AB  - Suicidal behavior is disproportionately frequent among inner-city Hispanic
      adolescent girls. In an attempt to generate a multifactorial set of hypotheses to
      explain this behavior, 33 such subjects consecutively admitted for suicidal
      behavior and 15 demographically identical nonsuicidal subjects were assessed by
      means of a structured interview. Mothers of all subjects were also assessed.
      Attempts were nearly always impulsive and nonlethal, though often with a stated
      wish to die. Nearly all were overdoses, and were precipitated by conflicts with
      mother or boyfriend. Mothers could usually identify the precipitants. Attempters'
      parents were less often born in the U.S., their mothers seemed medically less
      healthy, and their extended families were more often supported by public
      assistance, and had a higher incidence of criminal and psychiatric problems.
      School performance was poorer among attempters, who had suffered more and earlier
      losses, especially of biologic fathers, with whom fewer had ongoing
      relationships. They more often had boyfriends, had begun sexual activity, had
      recently lost friends, and expressed a mistrustful stance toward friendships.
      Similarly, their mothers had fewer friends and more often expressed a mistrustful
      stance. Relationships with mothers seemed more intense, desperate, and even
      violent, and attempters were much more often parentified, i.e., mothering their
      mothers. Although both groups often assumed caretaking roles in their families,
      attempters were more negatively described by themselves and by their mothers.
      While knowledge of suicidal models was common in both groups, attempters' mothers
      knew of even more models than did their daughters or the nonsuicidal subjects or
      their mothers. Notably, more attempters' mothers had themselves made attempts.
      Families of most attempters were usually mobilized by the attempt. These findings
      permit the construction of a putative profile of risk factors that can be tested
      more rigorously.

PMID- 1993521
TI  - Integration of medical and psychiatric management in self-mutilation.
AB  - The traditional management of factitious patients with self-inflicted injuries
      consists of medical/surgical treatment of the physical lesions, followed by
      psychiatric referral. The former is assigned to the dermatologist, the surgeon,
      or the primary care physician. More often than not, the subsequent psychiatric
      referral for treatment of the psychiatric disorder underlying and actually
      causing the self-mutilation fails because of self-mutilators' notorious
      resistance to psychiatric help. The integration of a psychiatric strategy into
      the medical management is more effective than a sequential division of
      medical/surgical and psychiatric treatment. This integrated treatment strategy is
      based on three key issues: education of the medical team in understanding the
      self-mutilation as a morbid form of help-seeking behavior, the judicious use of
      confrontation as a therapeutic tool, and the combination of psychotropic drug
      treatment with psychotherapeutic techniques.

PMID- 1993522
TI  - Length of stay in a general hospital psychiatric unit.
AB  - Fifty psychiatric inpatients with a prolonged length of stay were compared to 50
      control admissions for factors associated with prolonged hospitalizations in a
      general hospital. Seven variables were found to be significantly overrepresented
      among the long stayers, including treatment with electroconvulsive therapy,
      medical consultations, underemployment, dementia, disposition to a place other
      than home, absence of alcohol or drug abuse, and presence of psychosis without
      affective symptoms. The clinical and policy implications of these finding are
      discussed.

PMID- 1993523
TI  - Strategies for evaluating treatments for major depression in primary care
      patients.
AB  - Primary care physicians are being urged to provide patients experiencing a major
      depression treatments validated with psychiatric patients. The propriety of
      transferring clinical technologies from one care-giving sector to another is
      questionable, however, as it has little scientific support. We suggest that
      clinical trials be initiated so as to expand the available knowledge base. This
      paper analyzes the methodologic issues involved in pursuing such experimental
      research and urges that it be conducted despite the possible need for initial
      design compromises.

PMID- 1993524
TI  - Surveys show socioeconomic trends in diabetes.

PMID- 1993525
TI  - The RBRVS and hospitals: the physician payment revolution on our doorstep.
AB  - As the months count down to the scheduled Jan. 1, 1992, implementation of
      Medicare physician payment reform, physicians and hospital administrators are
      still uncertain as to precisely how the new payment rules will affect them. But
      when it does kick in, the Health Care Financing Administration's implementation
      of the resource-based relative value scale (RBRVS) is sure to transform both
      physician reimbursement and physician-hospital relations. Experts expect HCFA to
      use the RBRVS to raise reimbursement for primary care at the expense of specialty
      care; that could lead to tension between hospitals and specialty physicians, as
      those specialists pressure hospitals to help them make up for income losses.
      What's more, HCFA is already planning for the possibility that specialists hit by
      the RBRVS will raise their Medicare volume to recoup reimbursement declines. Just
      how successfully an individual hospital weathers the coming payment revolution
      will depend on its mix of specialties and its medical staff relationships. It's
      also clear, according to experts, that RBRVS implementation will create a strong
      incentive for hospitals to enter joint ventures or other arrangements with
      physicians for outpatient services.

PMID- 1993526
TI  - Hospitals: begin strategic planning for RBRVS.

PMID- 1993527
TI  - RBRVS creates incentive for hospital-physician outpatient care ventures.

PMID- 1993528
TI  - Exceptions process becoming the norm for PPS-excluded providers.
AB  - The worsening financial condition of providers exempt from Medicare's prospective
      pricing system (PPS) is driving more of those hospitals to seek exceptions from
      their payment limits. A major problem inherent in the current pricing system for
      PPS-excluded providers is its original intent as a temporary solution, policy
      experts say. The AHA has warned HCFA that "major structural changes in the health
      care delivery system" are imperiling the survival of a good number of PPS-exempt
      hospitals. Or, in the words of the CEO of a PPS-exempt Philadelphia
      rehabilitation hospital, "We are all on a collision course with disaster, and
      some of us have already arrived."

PMID- 1993529
TI  - Design & construction.
AB  - The deepening recession hasn't slowed hospital construction activity--at least
      not yet. While experts say health care executives should expect fewer large
      projects within the next two years, as the result of unpredictable sources of
      capital and increasing censure of hospital capital spending, for the moment
      hospital projects are helping to shelter some design and construction firms from
      the recession's fallout.

PMID- 1993530
TI  - Identifying your hospital's corporate culture.
AB  - Management experts say a key step in developing and improving an organization's
      corporate culture lies in first identifying that culture and defining it. "You've
      got a corporate culture whether you want it or not," says one academician.

PMID- 1993531
TI  - CEOs say patient deposits improve cash flow.
AB  - CEOs say it makes good business sense to require patients to make cash deposits
      toward their bills prior to admission, because improved cash flow is vital to
      financially strapped hospitals. But hospitals that require cash deposits should
      also be aware of the sensitive public relations issues involved, experts caution.

PMID- 1993532
TI  - Training of health care professionals must change, says Pew Commission director.
AB  - The Pew Health Professions Commission began its work to reform health
      professional education in a bold way last fall, issuing its recommendations up
      front in a push for immediate changes in the way health professionals are
      educated. And what needs changing? "I think that we in health care have to ask
      whether we've become seduced by specialization," says Edward H. O'Neil, the
      commission's executive director and assistant dean for medical education at Duke
      University.

PMID- 1993534
TI  - ProPAC scrutinizes financial impact of uncompensated care.

PMID- 1993533
TI  - Priorities? Heart, cancer, child/maternal care.

PMID- 1993535
TI  - New guide clarifies health care worker certification.

PMID- 1993536
TI  - Ruling highlights hospital antitrust liability concerns.

PMID- 1993537
TI  - Chronic care needs to be a higher priority.
AB  - Although acute care remains the focus of the U.S. health care delivery system, a
      shift is taking place toward chronic-illness mortality. Developing effective
      chronic-disease management processes is tough in the context of today's acute
      care orientation, according to William F. Henry, president of ForeSight Strategy
      Associates, St. Paul, MN.

PMID- 1993538
TI  - RBRVS: the importance of speculation.

PMID- 1993539
TI  - Cigarette smoking and cancer of the pancreas: evidence from a population-based
      case-control study in Toronto, Canada.
AB  - Results are reported with respect to smoking data from a population-based case
      control study of pancreatic cancer conducted in Toronto, Canada, between 1983 and
      1986. Lifetime smoking histories were obtained for 249 cases and 505 controls. A
      statistically highly significant positive association was observed between
      lifetime cigarette consumption and risk of pancreatic cancer. There was a rapid
      decrease in risk with time for those who quit cigarette smoking, the risk for ex
      smokers being the same as for lifetime non-smokers between 10 and 15 years after
      quitting. Limiting exposure to the 15 years prior to diagnosis considerably
      strengthens the association and leads to a much more clearly defined dose
      response relationship with relative risks of 1.88, 4.61, and 6.52 for tertiles of
      consumption for current cigarette smokers compared with lifetime non-smokers (p
      trend less than 10(-5)). We conclude that the current data, together with those
      from previous studies, strongly support a causal relationship between cigarette
      smoking and risk of pancreatic cancer, and indicate that cessation of smoking is
      likely to prove a rapidly effective preventive measure for this major type of
      cancer.

PMID- 1993540
TI  - Correlation between cytogenetic data and ganglioside pattern in human
      meningiomas.
AB  - Partial or total loss of chromosome 22 is often associated with tumors of the
      central nervous system and in particular with meningiomas. As in the case of
      other tumors, the ganglioside pattern is modified in transformed tissues.
      Cytogenetic analysis of 30 human meningiomas has been performed and the results
      compared to biochemical analysis of ganglioside distribution on the membrane
      surface. The meningiomas were divided into 2 groups on the basis of the presence
      or absence of chromosome 22. Thirteen tumors exhibited partial or total monosomy
      of the chromosome, whereas 17 were normal or showed other chromosomal anomalies.
      The GM3 and GD3 content of the meningiomas belonging to the 2 groups revealed a
      significant correlation between amount and reciprocal ratio of these 2
      gangliosides and cytogenetic data. Tumors with monosomy 22 had a higher content
      of ganglioside GD3 than samples without monosomy 22, where the main ganglioside
      was GM3. Other gangliosides such as GM1, GD1a, GD1b and GT were present in
      various amounts in the 2 groups. Considering the biosynthetic pathway of
      gangliosides, we hypothesize the involvement of a gene located on chromosome 22
      in the regulation of the enzymes which catalyze either GD3 synthesis
      (sialyltransferase 2, SAT-2) or its degradation to GM3 (neuraminidase).

PMID- 1993542
TI  - Socio-economic indicators, infectious diseases and Hodgkin's disease.
AB  - The relationship between socio-economic indicators, family size, history of
      tonsillectomy, infectious mononucleosis (IM) and other diseases and the risk of
      Hodgkin's disease (HD) was investigated in a hospital-based case-control study,
      conducted in the province of Pordenone, North-east Italy, between June, 1985 and
      March, 1990. One hundred and fifty-two HD cases (88 men and 64 women) and 613
      controls (357 men and 256 women) were interviewed. Patients with 14 or more years
      of education had a 2-fold increased HD risk (95% confidence interval, CI: 1.0
      3.9); such risk tended to be higher in patients with nodular sclerosis (NS) HD
      (odds ratio, OR: 4.4, 95% CI 1.8-11.0). Sibship size, birth order and
      tonsillectomy were not associated with HD risk. Cases and controls did not differ
      in the frequency or age at occurrence of common childhood infections. A history
      of IM, however, was found to be an important predictor of HD risk, in particular
      among NS HD (OR = 13.1, 95% CI 1.0-176.7). Past episodes of herpes zoster and of
      skin and genital warts were also associated with significantly increased HD
      risks. These data lend further support to the role of the IM agent (i.e., the
      Epstein-Barr virus) and, perhaps, of other viral infections and immunological
      alterations in the development of HD.

PMID- 1993541
TI  - Assessment of major carcinogens and alkaloids in the tobacco and mainstream smoke
      of USSR cigarettes.
AB  - Tobacco and mainstream smoke of USSR cigarettes were analyzed for carcinogens.
      The pH values of suspensions of the tobacco (5.4-5.6) and the nitrate content of
      the tobaccos (0.4-1.7%) were as expected for flue-cured and sun-cured tobaccos
      and mixtures thereof. The nicotine levels of the cigarette tobaccos (0.76-0.94%)
      and total alkaloid content (0.85-1.08%) were relatively low compared with
      tobaccos used in Western European and US cigarettes. The concentrations of
      tobacco-specific N-nitrosamines in the cigarette tobaccos were also low (N'
      nitrosonornicotine 0.36-0.85 microgram/g) compared with those in bright, oriental
      and blended cigarette tobaccos in Western countries (0.3-19 microgram/g). The 2
      non-filter and 4 filter cigarettes from the USSR had slow burning rates and
      yielded 14.0-16.7 puffs/cigarette, while puff yields for commercial cigarettes in
      Western countries average less than or equal to 11 puffs/cigarette. Consequently,
      tar and benzo(a)pyrene yields in the smoke of all cigarettes as well as
      nitrosamine yields were high, especially in the smoke of the filter cigarettes.
      It appears that an increase in the burning rates of these cigarettes should lead
      to lower smoke yields.

PMID- 1993544
TI  - Changes in cell kinetics induced by primary chemotherapy in breast cancer.
AB  - Changes in the 3H-thymidine labelling index (3H-TdR LI) of primary tumor induced
      by cytoreductive chemotherapy were evaluated in 26 patients with locally advanced
      breast cancer subjected to mastectomy after different systemic therapies. A
      significant reduction of 3H-TdR LI by primary chemotherapy was observed in 11
      cases. Changes in cell kinetics were related to the pretreatment proliferative
      activity: significant increases were observed in 70% of tumors with a very low 3H
      TdR LI (less than 25%) and significant decreases in 100% of tumors with a very
      high 3H-TdR LI (greater than 7.0%). There was no correlation between pretreatment
      3H-TdR LI and the objective clinical response, which was conversely related to
      posttreatment cell kinetics. The 2-year progression rate was lower for patients
      whose residual tumors after treatment had remained (2/7) or become (1/8) slowly
      proliferating than for patients whose tumors had remained (5/7) or become (4/4)
      rapidly proliferating.

PMID- 1993543
TI  - Bilateral ovarian carcinoma: cytogenetic evidence of unicentric origin.
AB  - Cytogenetic analyses were performed on the tumors from both ovaries in 15
      patients with bilateral ovarian carcinoma. In 4 of them, omental implants were
      also examined. Abnormal karyotypes were detected in 11 cases. The baseline
      karyotypes in the 2 tumorous ovaries were identical in each patient, indicating
      that bilateral ovarian cancer develops by metastatic spreading. There was no
      clear-cut evidence of differences in the clonal evolution between the tumors of
      the 2 ovaries, and hence the side harboring the primary tumor could never be
      determined. The metastatic nature of the omental implants was proved by the fact
      that their karyotypes were indistinguishable from those of the ovarian tumor
      tissue.

PMID- 1993545
TI  - Coffee and alcohol as determinants of risk of pancreas cancer: a case-control
      study from Toronto.
AB  - Results are reported from a population-based study of 249 cases of pancreas
      cancer and 505 controls carried out in Toronto, Canada, between 1983 and 1986.
      Lifetime consumption of coffee and alcohol and medical histories were assessed by
      personal interviews. No evidence of any association was found with different
      types of coffee or alcohol after adjusting for smoking, calories and fibre
      intake. There was a significant increased risk associated with a history of
      diabetes mellitus within 5 years of cancer development. A protective effect of a
      history of some allergic conditions, hay fever, eczema and asthma, was observed,
      although the relative risks were not significant (p value greater than 0.10).

PMID- 1993546
TI  - Is the incidence of colorectal cancer related to reproduction? A prospective
      study of 63,000 women.
AB  - Relationships between reproductive factors and risk of colorectal cancer were
      examined in a population-based prospective study in Norway. Available for
      analysis were 831 cases (581 colon cancer, 250 rectal cancer) diagnosed in a
      cohort of 63,090 women, surveyed in 1956-1959 and followed through 1980. Overall,
      the analyses showed no strong effects of reproductive factors. In particular,
      high parity was not associated with reduced risk, and late age at first or last
      birth was not associated with an increased overall risk. However, in age-specific
      analyses of colon cancer, adverse effects of late age at first birth and late age
      at last birth were observed in women with cancer diagnosed before the age of 60.
      A non-significant overall excess risk in parous compared to nulliparous women was
      strongest for women with a cancer diagnosis before the age of 50 years. Having
      had many abortions was associated with increased risk for all sub-sites. Neither
      age at menarche nor age at menopause were related to risk of colorectal cancer.
      The results suggest that reproductive factors, which are of importance in the
      etiology of cancer of the breast and genital organs in women, are not similarly
      related to risk of colorectal cancer.

PMID- 1993547
TI  - Cytotoxic and cytostatic effects of arecoline and sodium nitrite on human cells
      in vitro.
AB  - Arecoline, an active alkaloid of Areca catechu L., and sodium nitrite, a food
      additive, are highly cytotoxic and cytostatic on the Hep 2 cell line when
      administered in an acidic environment (pH 4.2) in the presence of S-9 mixture.
      Hep 2 cells (10(6)) were treated with either 0.145, 0.725 or 1.449 mM sodium
      nitrite or 0.042, 0.085 or 0.339 mM arecoline or sodium nitrite (0.145 mM) plus
      varied concentrations of arecoline (0.042, 0.085 or 0.339 mM). Their effects were
      additive in nature. Hep 2 cells exposed to this combination showed reduced cell
      survival, and lower rates of DNA and protein syntheses. Involvement of N-nitroso
      derivatives of arecoline is suggested to explain the results. On the basis of
      these studies, we speculate that N-nitroso compounds derived from arecoline can
      (weakly) interact with DNA.

PMID- 1993548
TI  - Inhibition by neurotensin of azaserine-induced carcinogenesis in rat pancreas.
AB  - The effect of neurotensin on pancreatic carcinogenesis induced by azaserine was
      investigated in Wistar rats. Rats were given weekly injections of 10 mg/kg body
      weight of azaserine for 25 weeks and 200 micrograms/kg body weight of neurotensin
      in depot form every other day for 62 weeks. Carcinogen-induced pancreatic lesions
      were examined by histochemical techniques, and were classified as ATPase-positive
      or ATPase-negative. In week 62, quantitative histological analysis showed that
      prolonged administration of neurotensin significantly reduced the volume (as
      percent of parenchyma) of ATPase-positive pancreatic lesions, which are closely
      correlated with the ultimate development of pancreatic cancer. Histologically,
      pancreatic adenocarcinomas occurred at a significantly lower rate in rats treated
      with neurotensin than in untreated rats. Administration of neurotensin also
      significantly decreased the labelling indices of carcinogen-induced pancreatic
      lesions, but not of the surrounding acinar cells. These findings indicate that
      neurotensin inhibits pancreatic carcinogenesis, and that this may be related to
      the reduction of ATPase-positive lesions and to the inhibition of cell
      proliferation in neoplastic lesions of the pancreas.

PMID- 1993549
TI  - A correlation between GM-CSF gene expression and metastases in murine tumors.
AB  - Using 14 transplantable murine tumors, we investigated a possible correlation
      between their ability to produce the cytokine GM-CSF and the spontaneous
      metastatic potential when mice were subcutaneously inoculated. The following
      results were obtained: (1) seven tumors, which produced severe pulmonary
      metastases and metastatic swelling of lymph nodes, exhibited the ability to
      produce GM-CSF activity in culture. The cell population analysis revealed that
      the cells producing GM-CSF were tumor cells themselves, but that contaminating
      macrophages/granulocytes and T lymphocytes did not produce GM-CSF. The mRNA for
      GM-CSF was also found in all of these highly metastatic tumors tested. In mice
      inoculated with a highly metastatic tumor, the GM-CSF mRNA was also found in
      lungs; (2) in 3 other tumors, which produced histological but not macroscopical
      pulmonary metastases, no GM-CSF activity could be detected in the culture fluids.
      GM-CSF mRNA was, however, detected in the tumor cells in the presence of an mRNA
      stabilizing agent, cycloheximide, suggesting the possibility that the tumor cells
      of this type were transcribing GM-CSF gene, and secreting it in undetectable
      levels; (3) in culture of the 4 remaining poorly or non-metastatic tumors,
      neither CSF activity nor GM-CSF mRNA could be detected even in the presence of
      cycloheximide. GM-CSF mRNA was also not found in lungs of tumor-bearing mice. Our
      results indicate that there may be a correlation between GM-CSF gene expression
      in tumor cells and spontaneous metastases.

PMID- 1993550
TI  - Production of fibronectin by human tumor cells and interaction with exogenous
      fibronectin: comparison of cell lines obtained from colon adenocarcinomas and
      squamous carcinomas of the upper aerodigestive tract.
AB  - Cell lines derived from 13 different human colon adenocarcinomas were examined
      for production of fibronectin by ELISA and for cell-surface expression of
      fibronectin by indirect immunofluorescence. Two squamous epithelial cell lines
      obtained from tumors of the upper aerodigestive tract were used as controls. None
      of the 13 colon carcinoma lines produced detectable amounts of fibronectin or
      showed detectable cell-surface staining with anti-fibronectin. The 2 squamous
      epithelial cell lines, in contrast, produced large amounts of fibronectin which
      could be detected in the culture medium and bound to the substratum. The squamous
      carcinoma cells also stained brightly when examined in the viable state by
      immunofluorescence with anti-fibronectin. In addition to being studied for
      fibronectin production, each cell line was also examined for the ability to
      interact with exogenous fibronectin in an adhesion assay. None of the colon
      carcinoma cells were adherent to fibronectin-coated culture dishes while the 2
      squamous carcinoma cells rapidly attached and spread on this substratum. These
      data suggest that cell lines derived from adenocarcinomas of the colon are
      deficient in production of fibronectin and in their ability to interact with
      exogenous fibronectin. In their degree of deficiency, the colon carcinoma cells
      are significantly different from several different types of human tumor cell. The
      failure of the colon carcinoma cells to synthesize detectable amounts of
      fibronectin endogenously or to interact with exogenous fibronectin may explain,
      in part, the low degree of adhesive interaction which these cells have for their
      substratum. This, in turn, may influence the in vitro and in vivo properties of
      colon carcinoma cells.

PMID- 1993551
TI  - Identification and characterization of a colon-cancer-associated antigen
      expressed on leukemia-lymphoma cell lines.
AB  - A total of 72 human leukemia-lymphoma cell lines were studied for reactivity with
      the monoclonal antibody (MAb) A7, an anti-human colon-cancer-cell-associated
      antigen reagent, by indirect membrane immunofluorescence. Nine of the 72 cell
      lines expressed the antigen recognized by A7 MAb. Five of the 34 T-cell lines, 2
      of the 21 B-cell lines, and 2 of the 3 non-lymphoid-non-myeloid cell lines were
      reactive with A7 MAb. By means of SDS-PAGE and immunoblotting, the antigens
      isolated from both colon cancer cell lines (WiDr, SW1116 and LoVo) and leukemia
      cell lines (A3/KAWAKAMI, H9, RPMI 8226 and SPI-801) showed an identical MW of 42
      43 kDa. The non-glycosylated antigen recognized by A7 MAb, which was expressed on
      both the colon cancer line (SW1116) and the leukemia line (H9) in the presence of
      tunicamycin, also showed an identical MW of 36 kDa. However, the quantity of the
      antigen in the leukemia cells was significantly lower than in the colon cancer
      cells. Although expression of this colon-cancer-associated antigen in the non
      colon cancer cells is real, the significant expression of this antigen in colon
      cancer cells makes it useful for clinical monitoring of colon cancer patients.

PMID- 1993552
TI  - Tumor-cell lysis by in-situ-activated human peripheral-blood mononuclear cells.
AB  - A heteroconjugate (HC) was synthesized between OKT3 and monoclonal antibody (MAb)
      7E8, which specifically reacts with the tumor marker placental alkaline
      phosphatase (PLAP). Similarly to OKT3, in vitro, the HC induced a dose-dependent
      proliferation response of human peripheral-blood mononuclear cells (PBMCs) and,
      in concert with rIL-2, it progressively activated T cells over a 4-day period. In
      co-cultures of continuously activated PBMCs and MO4 tumor cells (non-MHC
      restricted mouse fibroblasts transfected with the cDNA for PLAP), the HC (25
      ng/ml), again acting in concert with rIL-2, induced specific lysis of the MO4
      cells. This process occurred progressively over 2 to 3 days and was monitored
      from the release in the supernatant fluid of cellular 3H-L-leucine, but also from
      analyses involving the remaining non-lysed cancer cells, i.e., by estimates of
      their protein content, by measurements of their viability, and most accurately by
      determinations of their PLAP content. Antibody 7E8 by itself induced a weak tumor
      cell lysis (ADCC), potentiated by the addition of rIL-2. However, after 7 days of
      PBMC-preactivation with the HC and rIL-2, antibody 7E8 no longer mediated any
      ADCC, whereas the HC-dependent lysis was further potentiated. The observed
      proliferation of T cells and development of cytotoxicity at low concentrations of
      HC and rIL-2 support the idea that a moderate but continuous T-cell activation
      combined with T-cell targeting is sufficient for the induction of progressive and
      efficient tumor-cell lysis.

PMID- 1993553
TI  - Enhancement of natural-killer-cell susceptibility of human breast-cancer cells by
      estradiol and v-Ha-ras oncogene.
AB  - Natural killer (NK) cells are putative components of the cellular immune response
      to transformed cells. Since both estradiol treatment and ras-oncogene
      overexpression enhance tumorigenicity of hormone-dependent breast-cancer cells,
      we studied the effects of estrogen and of the activated v-Ha-ras oncogene on NK
      susceptibility of MCF-7 human breast-cancer cells. MCF-7 cells were sensitive to
      cytolysis mediated by resting and IL2-activated peripheral-blood non-adherent
      lymphocytes. Lysis appeared to be mediated by NK cells, since it was abrogated by
      treatment of effector cells with alpha-CD16 monoclonal antibody (MAb) plus
      complement (c'). Estradiol treatment of MCF-7 cells was able to significantly
      increase their sensitivity to the lysis by IL2-activated and unactivated
      peripheral-blood lymphocytes, as early as 24 hr throughout 10 days of hormone
      treatment. Hormone-insensitive, estrogen-receptor-negative breast-cancer cells
      (BT20) did not change their NK susceptibility after estradiol treatment.
      Increased NK susceptibility was also observed in v-Ha-ras-transfected and
      oncogene product overexpressing MCF-7 cells (MCF-7-ras) with respect to cells
      transfected with the selectable gene marker gpt alone (MCF-7-gpt). Overexpression
      of v-Ha-ras appeared to be able to bypass the need for estrogen to increase NK
      susceptibility, since estradiol-treated MCF-7-ras cells were not lysed more than
      untreated MCF-7-ras cells. The enhancement of NK susceptibility observed after
      both estradiol treatment and v-Ha-ras overexpression suggests that the hormone
      mediated and the ras-oncogene-mediated signalling systems share events involved
      in the control of tumor-cell/host-effector-cell interactions.

PMID- 1993554
TI  - Growth regulation of the AML-193 leukemic cell line: evidence for autocrine
      production of granulocyte-macrophage colony-stimulating factor (GM-CSF), and
      inhibition of GM-CSF-dependent cell proliferation by interleukin-1 (IL-1) and
      tumor necrosis factor (TNF alpha).
AB  - The human leukemic cell line AML-193 was tested for its proliferative response to
      endogenously produced autocrine factors and to a variety of cytokines and colony
      stimulating factors. Cells grown in the absence of GM-CSF incorporated tritiated
      thymidine, and this was partially reversed by adding neutralizing anti-GM-CSF
      antibodies to the culture medium, suggesting that it was due, at least in part,
      to autocrine GM-CSF production. This was confirmed by immunopurification of a GM
      CSF-like activity from cell supernatant of AML-193 cells grown in serum free
      medium in the absence of exogenous GM-CSF. When AML-193 cells were cultured with
      GM-CSF in combination with other cytokines, Interleukin-1 alpha and beta (IL-1
      alpha and beta), Interleukin-3 (IL-3), Interleukin-6 (IL-6), granulocyte colony
      stimulating factor (G-CSF) and tumor necrosis factor alpha (TNF alpha), none of
      them affected the concentration of GM-CSF required to induce 50% of maximum
      proliferation (D50). However, the maximum proliferation induced by GM-CSF alone
      was drastically decreased by IL-1 alpha, IL-1 beta and TNF alpha. Inhibition
      caused by exposure of the AML-193 to IL-1 for up to 24 hr was reversible, ruling
      out a direct cytotoxic effect.

PMID- 1993555
TI  - Differential role of transforming growth factor-alpha in two human colon
      carcinoma cell lines.
AB  - Antibodies to epidermal-growth-factor receptor (EGF) and transforming growth
      factor-alpha (TGF-alpha) were used to determine the role of endogenous TGF-alpha
      in the growth of 2 human colon-carcinoma cell lines. Both the GEO and HCT 116
      colon-carcinoma cell lines secrete similar levels of TGF-alpha and have similar
      numbers of low-affinity binding sites for EGF. However, the HCT 116 cells lack
      the high-affinity EGF binding site present on the GEO cells. The anti-EGF
      receptor antibodies effectively blocked the binding of 125I-EGF to the GEO and
      HCT 116 cell lines. Growth of the GEO cell line was inhibited 50-80% by the anti
      EGF receptor and anti-TGF-alpha antibodies. When the same antibodies, in
      sufficient amounts to block binding of TGF-alpha to the cells, were added to the
      HCT 116 cell line, no effect on growth was seen. These results suggest that while
      the GEO cell line utilizes TGF-alpha in an autocrine manner, the TGF-alpha
      secreted by the HCT 116 cells apparently does not play a role in the growth of
      these cells.

PMID- 1993556
TI  - Retinoic-acid-induced differentiation prevents gene amplification in
      teratocarcinoma stem cells.
AB  - In an attempt to study the regulatory properties of cells required for gene
      amplification, the capacity for amplification of the dehydrofolate reductase gene
      (dhfr) was determined in F9 teratocarcinoma stem cells during differentiation. By
      stepwise selection of surviving cells exposed to progressively increasing
      concentrations of methotrexate (MTX) up to 1,000 microM within 4 months, non
      differentiated F9 cells reached a more than 40-fold amplification of their dhfr
      gene, elevated levels of dhfr mRNA and a 5-log increase in MTX resistance.
      Exposure to 5 Gy of 60Co-gamma-irradiation accelerated the process of
      amplification. In contrast, F9 cells that had been differentiated to endodermal
      cells by treatment with retinoic acid (RA) did not grow in MTX concentrations
      above 0.1 microM, either with or without radiation pretreatment and did not
      amplify the dhfr gene to any measurable extent over the same period of time. Upon
      treatment of methotrexate-resistant (F9-MTXr) cells with retinoic acid, loss of
      the amplified DNA in the absence of selection was significantly retarded. The
      ability to amplify the dhfr gene was correlated with the occurrence of origin
      binding activity in vitro (early domain of SV40 minimal origin of replication).
      These data indicate an increase in genomic stability and rigorous control of
      origin activity by differentiation.

PMID- 1993558
TI  - Psoriatic arthritis.

PMID- 1993557
TI  - Differential influence of organ site on three subpopulations of a single mouse
      mammary tumor at two distinct steps in metastasis.
AB  - Tumor subpopulations 66c14, 168FARN, and 4T07 are drug-resistant variants
      selected from sister subpopulations derived from a single mouse mammary tumor.
      These subpopulations are heterogeneous in their capacities to form experimental
      metastatic growth in the lungs and liver. Initial survival kinetics of arrested
      cells, determined by the clearance of 125IUdR-labelled cells, and subsequent
      growth rates, determined by sequential recovery of clonogenic tumor cells from
      occult metastases, both correlated with organ-colonizing potential as determined
      by necropsy. The growth rates of these 3 subpopulations were determined in vitro
      in monolayer and in situ in the subcutis, in the liver following intrasplenic
      injection, and in the lung following intravenous injection. Clonogenic potential
      of all 3 lines was similar in vitro (54-59%). Growth rates in vitro (population
      doubling times 16.5-21 hr) and in the subcutis (tumor volume doubling times 5.2
      7.4 days) were similar for the 3 subpopulations, but differed significantly in
      the liver and lungs. For line 4T07, the most metastatic line to both lung and
      liver, population doubling times in vitro and in the lung and liver were similar,
      ranging from 17 to 26 hr. For lines 66c14 and 168FARN, the growth rates in lungs
      and livers were much slower than in vitro. Line 66c14, which is relatively more
      metastatic to the lungs, grew much faster in the lung (39 hours) than in the
      liver (91 hr), but line 168FARN, which is relatively more metastatic to the
      liver, grew at a faster rate in the liver (37 hr) than in the lung (63 hr). Thus,
      3 tumor subpopulations (seeds) derived from a single tumor were differentially
      affected by host organ factors (soil) at 2 distinct stages in the metastatic
      process.

PMID- 1993559
TI  - The mast cell in fibrosis.

PMID- 1993560
TI  - Acanthosis nigricans.

PMID- 1993561
TI  - Psychologic characteristics of men with alopecia androgenetica and their
      modification.
AB  - Psychologic characteristics were studied in a sample of 168 men with alopecia
      androgenetica who participated in a clinical trial on the efficacy of minoxidil
      gel. In general, no evidence of psychologic malfunctioning was found. Instead, a
      slightly more adequate psychologic state was indicated. However, specific
      problems associated with hair loss were reported by a substantial number of men.
      Responders with cosmetic improvement in the group over 35 years of age improved
      more regarding general psychologic maladjustment, inadequacy, and self-evaluation
      than those who did not respond. A reverse trend was, however, found in the group
      younger than 35 years of age, where the nonresponders improved more. An
      explanation for these findings is derived from the theory of cognitive
      dissonance.

PMID- 1993563
TI  - Reticulate nonmelanocytic hyperpigmentation anomaly. A probable variant of
      Dowling-Degos disease.
AB  - A 26-year-old white woman had reticulate nonmelanocytic hyperpigmentation anomaly
      characterized by partially blanching red-brown papules and macules and a
      histologic picture of digitate epithelial budding proliferation with lightly
      pigmented rete ridges. Except for the classically described hyperpigmentation at
      the rete ridge tips, the patient has Dowling-Degos disease. This case of a
      reticulate nonmelanocytic hyperpigmentation anomaly is probably a variant of
      Dowling-Degos disease.

PMID- 1993562
TI  - HLA in bullous pemphigoid. The probable role of HLA-B7 as a marker for poor
      responders to immunosuppressive therapy.
AB  - The frequency of HLA-class I and DR antigen frequencies were studied in 38 (class
      I) and 19 (DR) patients with bullous pemphigoid, respectively, and compared with
      controls. There was no important difference in the frequency of HLA-A,B,C, and DR
      antigens between patients and controls. An increase in the HLA-B7 frequency in
      poor responders to immunosuppressants (50% vs. 27% in the control group and vs.
      13% in the group of all patients) was noticed, and the possible role of this
      antigen as a marker for poor responders to therapy was suggested.

PMID- 1993564
TI  - Pigmentary effects from the protracted infusion of 5-fluorouracil.

PMID- 1993565
TI  - Chronic zinc deficiency in a patient with psoriasis and alcoholic liver
      cirrhosis.

PMID- 1993566
TI  - Multiple hamartoma syndrome with acromegaloidism.

PMID- 1993567
TI  - Esophageal web in generalized epidermolysis bullosa.

PMID- 1993568
TI  - Treatment of Behcet disease with indomethacin.
AB  - Thirty patients with Behcet disease (BD) were treated with oral indomethacin 25
      mg four times daily for 3 months as an open label study. The study population
      consisted of 13 women and 17 men from 15 to 45 years of age (mean 27 years). At
      the initiation of the therapy, 28 patients had oral aphthous lesions, 23 had
      joint involvement, 13 had genital ulcerations, 8 had cutaneous lesions, and 4 had
      eye involvement. Eighty-eight percent of patients with skin lesions, 80% with
      joint involvement, 43% with oral aphthous lesions, and 38% with genital
      ulcerations responded to indomethacin therapy. In three patients indomethacin was
      changed to the suppository form due to gastrointestinal side effects. Although it
      is difficult to assess the efficacy of indomethacin in BD because of the
      intermittent nature of symptoms, the majority of patients showed improvement in
      their symptoms of arthritis and skin lesions. This study indicates that
      indomethacin can be used as effective therapy particularly in patients with joint
      involvement.

PMID- 1993569
TI  - Treatment of squamous cell carcinoma with interferon.
AB  - Human natural leukocytic interferon and recombinant HulFN alpha 2c can be used in
      the therapy of squamous cell carcinoma. The duration of treatment was 3-6 weeks.
      A single dose was 400,000-5,000,000 units given weekly for 3-6 weeks. Clinically
      and histologically 19 of 32 patients were cured and tumor cells were not found in
      the material taken after interferon treatment for the second biopsy. In ten
      patients tumor size was reduced 25-90%, and in three patients tumor size was not
      reduced according to clinical findings. With recombinant HulFN alpha 2c therapy
      given 5 times per week for 4 weeks. Four of ten patients with similar tumors were
      cured clinically and histologically clinical findings. In five patients tumor
      size was reduced 25-90%, while in one patient there was no reduction in tumor
      size. Both types of interferons are effective in the treatment of squamous cell
      carcinoma. Side reactions were mild.

PMID- 1993570
TI  - 1 alpha,25-(OH)2D3 use on psoriasis and ichthyosis.
AB  - The present work compared the clinical efficacy of topically applied 1 alpha,25
      dihydroxyvitamin D3 (1 alpha,25-(OH)2D3) in 16 cases with psoriasis vulgaris, 5
      with ichthyosis vulgaris and 8 with X-linked ichthyosis. Sixty-nine percent of
      the psoriatic cases responded to 1 alpha,25-(OH)2D3 therapy, whereas no
      ichthyotic patients responded. The present study confirms the previously
      suggested effectiveness of the active form of vitamin D3 for psoriasis and denies
      its possible efficiency against the ichthyoses. Direct suppression of
      hyperproliferative activity of the psoriatic epidermis is considered one of the
      most plausible mechanisms of 1 alpha,25-(OH)2D3 efficacy, through examination of
      the aforementioned evidence.

PMID- 1993571
TI  - Bookplates of dermatologists.

PMID- 1993572
TI  - Traumatic baldness of the tongue.

PMID- 1993573
TI  - Multiple penile syringomas mimicking verrucae.

PMID- 1993574
TI  - Stress and psoriasis. Psychoneuroimmunologic mechanisms.

PMID- 1993575
TI  - Alterations in glial cell morphology and glial fibrillary acidic protein
      expression in urethane-induced retinopathy.
AB  - Urethane injection in newborn rats causes a photoreceptor degeneration without
      initial damage to the retinal pigment epithelium, choriocapillaris, or inner
      retina. In later stages, retinal vessels become incorporated into the retinal
      pigment epithelium (RPE) and change from a continuous endothelial cell phenotype
      to a fenestrated phenotype. At the light-microscopic level, there do not appear
      to be morphologic changes in the inner retina up to 24 weeks of age.
      Ultrastructurally, however, there are alterations in Muller cell cytotopographic
      organization. In the normal retina, intermediate filaments are primarily found
      from the ganglion cell layer to the inner nuclear layer. These filaments do not
      show glial fibrillary acidic protein immunoreactivity (GFAP-IR) in the normal
      animal. In the urethane-treated animals, the compartmental organization of the
      Muller cell organelles is moved vitread. Intermediate filaments are found in the
      end-foot region, and in the inner plexiform layer, bundles of intermediate
      filaments become more prominent. All of these filaments are GFAP-IR positive. The
      new expression of GFAP in the Muller cell may be linked to the observed
      rearrangement of the cytoskeletal elements. In urethane-induced retinopathy, GFAP
      IR is found associated with vessels in all layers of the remaining retina.
      However, it is not seen accompanying vessels into the RPE. Ultrastructurally,
      there is no glial investment of the RPE-associated vessels. This absence of glial
      investment may permit the change in phenotype observed in these vessels.

PMID- 1993576
TI  - Biological control of primate macular pigment. Biochemical and densitometric
      studies.
AB  - The amounts of zeaxanthin (Z) and lutein (L), the carotenoids constituting the
      primate macular pigment, were measured in the central retinas of monkeys (Saimiri
      sciureus and Macaca fascicularis). Two independent methods--reverse-phase high
      performance liquid chromatography (HPLC) and microdensitometry--were used for
      analysis of the same set of retinas. Most of the measurements were made on
      retinas that had been fixed by glutaraldehyde-paraformaldehyde perfusion of the
      animal. Control experiments showed that this fixation did not interfere with the
      quantitative extraction and analysis of the carotenoids. The amount of macular
      pigment calculated from microdensitometry of the foveal region was proportional
      to the amount of pigment assayed by HPLC of the same retinal area, demonstrating
      that either method can be used reliably to rank the carotenoid content of
      aldehyde-fixed foveas. The optical density of pigment in the axial direction
      through the retina was higher than would be predicted if the pigment were
      randomly oriented. This is consistent with the idea that the nonrandom
      orientation of the dichroic macular pigment molecules found in previous studies
      contributes to increased optical filtering of the retinal image. Comparisons of
      the amounts of Z and L between the left and right eyes of the same monkey, within
      1 mm of the foveal center, always showed excellent agreement (averaging a 5%
      difference for Z and 11% difference for L), whereas differences among individual
      monkeys were very large (up to fourfold for Z). These results indicate that the
      uptake and assimilation of the macular carotenoids are biologically regulated by
      selective mechanisms in primate retinas.

PMID- 1993577
TI  - Distribution of individual macular pigment carotenoids in central retina of
      macaque and squirrel monkeys.
AB  - The spatial distribution of lutein (L) and zeaxanthin (Z), the structural isomers
      composing the macular pigment, was studied in the retinas of macaque monkeys
      (Macaca fascicularis) and squirrel monkeys (Saimiri sciureus). Spatial profiles
      of macular pigment optical density were obtained from retinal whole mounts. Then
      concentric annuli were microdissected from the fovea and adjacent regions of the
      same retinas. Each retinal segment was analyzed for carotenoids by high
      performance liquid chromatography. Both L and Z reached their highest
      concentrations at the center of the fovea and declined monotonically with
      eccentricity for both primate species. This is inconsistent with a preferential
      association of L with rods. Macaque monkeys have a consistent pattern of more Z
      than L at the foveal center, like humans. Z declines more rapidly than L with
      eccentricity, so that L becomes dominant in the periphery. Squirrel monkeys (all
      male) showed striking individual differences. Some had more Z than L at the
      foveal center like macaques, but four of six had the reverse pattern, with more L
      than Z throughout the central retina. Individual differences among squirrel
      monkeys may be linked to their color vision polymorphisms. This suggests that a
      particular Z/L ratio in primate retinas may be associated with a specific cone
      phenotype, just as particular carotenoids are associated with specific cone types
      in vertebrates with cone oil droplets.

PMID- 1993578
TI  - A comparative study of methods of photoreceptor morphometry.
AB  - A comparative study was performed to compare methods of quantitative evaluation
      of damage to photoreceptor cells in rat eyes exposed to light. Using a manual
      count of individual photoreceptor nuclei as the standard, the following
      measurements were compared: (1) outer nuclear layer column count, (2) area, (3)
      thickness, and (4) the number of nuclei of the outer nuclear layer of the retina
      using a newly developed computer program that counts a digitized image. Linear
      regression analysis of the data showed that the computer method was the most
      accurate with a Pearson correlation coefficient of 0.9911. The other methods
      tested also correlated well with the manual count, with coefficients ranging from
      0.9367-0.9532. All these methods were reasonably accurate measurements of
      photoreceptor layer integrity, with the computer count most closely approximating
      the values obtained by a manual count. However, the outer nuclear layer thickness
      measurement appeared to be the fastest and most convenient method to evaluate
      photoreceptor cell damage quantitatively. Computer counting could be reserved for
      situations in which a high degree of accuracy is required.

PMID- 1993579
TI  - Rod- and cone-associated interphotoreceptor matrix in the rat retina. Differences
      in light-evoked distributional changes.
AB  - Several of the components of the interphotoreceptor matrix (IPM) in the rat have
      recently been shown to undergo a light-evoked shift in distribution or molecular
      conformation. In the light, the IPM appears concentrated at the apical surface of
      the retinal pigment epithelium (RPE) and in the basal outer segment region at the
      inner and outer segment junction, with relatively little present in the
      intervening interstitial zone adjacent to the outer segments. By contrast, the
      IPM in the dark is distributed almost uniformly across the outer segment layer.
      In the present study, the authors explored whether specialized domains of IPM
      known as the cone matrix sheaths undergo light-induced changes similar to those
      previously shown for the IPM as a whole. Fluorescence lectin histochemistry was
      used on retinal sections of light- and dark-adapted rats with lectins that show
      selective or preferential binding to cone matrix sheaths, peanut agglutinin
      (PNA), and Ricinus communis agglutinin (RCA-1). Lectin binding to cone matrix
      sheaths was the same in both lighting conditions, unlike the rod-associated IPM.
      These experiments and others using pretreatment of sections with neuraminidase
      suggested different roles of RCA-1 and PNA-binding components of the IPM in
      different photoreceptor-RPE cell interactions, including the transfer of
      substances between the two cell types and retinal adhesion.

PMID- 1993580
TI  - Primitive neuroectodermal tumor of the midbrain in a murine model of
      retinoblastoma.
AB  - The first heritable model of retinoblastoma was established by retina-specific
      expression of simian virus 40 T-antigen (SV40 T-ag) in transgenic mice.
      Bilateral, multifocal ocular tumors were observed in 100% of transgene-bearing
      mice. Central nervous system neoplasms occurred at a lower rate (27%) and
      represented the murine counterpart of human trilateral retinoblastoma. The
      authors characterized the transgenic brain tumors and found them to be primitive
      neuroectodermal tumors (PNET) of the midbrain. Murine brain tumors do not involve
      the pineal gland and most closely resemble undifferentiated suprasellar or
      parasellar tumors occasionally observed in human trilateral retinoblastoma. The
      murine malignancies arose from the subependymal cells of the cerebral aqueduct.
      Immunohistochemical and ultrastructural examination revealed that the transgenic
      brain tumors were undifferentiated and lacked all antigens associated with normal
      murine neuronal, glial, and ependymal cells.

PMID- 1993581
TI  - The distribution of retinol-binding protein and its mRNA in the rat eye.
AB  - Although a constant supply of retinol is a critical requirement for the visual
      cycle, the molecular mechanisms underlying retinol delivery, uptake, storage, and
      transport in the eye are not well understood. Previously the synthesis of serum
      retinol-binding protein (RBP) in the mammalian eye was reported. Now the
      distribution of RBP and RBP mRNA in the rat eye has been studied by
      immunohistochemical and in situ hybridization techniques has been studied. The
      RBP mRNA was present only in the cytoplasm of retinal pigment epithelial (RPE)
      cells, terminating abruptly at the pars plana. On the other hand, RBP
      immunoreactivity was more widespread. The most intense immunostaining was present
      in retinal ganglion cells, the corneal endothelium, and under certain conditions
      of tissue fixation, the corneal epithelium. Consistent but less intense
      immunoreactivity was detected in the photoreceptors, Muller cells, inner
      plexiform layer, ciliary epithelium and stroma, iris epithelium, retinal pigment
      epithelium, lacrimal glandular epithelium, and periorbital soft tissues. These
      findings suggest that RBP synthesized by the RPE may be secreted to various
      ocular locations. However, at present, uptake from plasma cannot be excluded as
      another possible source of ocular RBP. In the plasma, holo-RBP (the retinol-RBP
      complex) is transported in complex with another plasma protein, transthyretin
      (TTR). This substance is also synthesized by the RPE and its distribution in the
      eye is similar to that described for RBP. Taken together, these findings support
      the proposal that ocular RBP and TTR may function cooperatively in the
      intraocular translocation of retinol.

PMID- 1993582
TI  - Effect of decreased retinal illumination on simultaneously recorded pattern
      electroretinograms and visual-evoked potentials.
AB  - Sixteen normal subjects and three patients with optic neuritis were studied to
      determine the effect of decreased retinal illumination on simultaneously recorded
      pattern electroretinograms (PERG) and visual-evoked potentials (VEP). Using
      neutral-density filters (NDF), it was found that linear modeling is an excellent
      fit for VEP/PERG amplitudes and latencies as log functions of retinal
      illumination, both for individual eyes and averages of pooled data. Within narrow
      statistical limits, regression slopes show that mean PERG B-wave and VEP P100
      latencies are affected almost identically by decreased illumination, leaving the
      mean retinocortical time (RCT) virtually unchanged. However, mean B-wave
      amplitude was greatly reduced at retinal illuminations at which P100 amplitude
      was unaffected. Of clinical significance was that these latency and amplitude
      effects were found in each eye tested, whether normal or pathologic. In
      particular, the RCT in normal subjects was never found to be statistically
      abnormal due to decreased retinal illumination, and it faithfully represented the
      optic nerve lesion in the patients with optic neuritis. This result was applied
      to a population of eight patients with uncomplicated cataracts. The significance
      of these results is discussed.

PMID- 1993583
TI  - Glycoproteins in the retinal pigment epithelium of normal and dystrophic rats.
AB  - The apical membranes of retinal pigmented epithelium (RPE) were isolated from
      adult, normal (LE), and dystrophic (RCS) rats. The proteins of these RPE
      subfractions were separated through the use of sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. The lectin-binding properties of
      glycoproteins were examined in western blots through the use of lectin-peroxidase
      conjugates. No differences were detected between RPE membrane proteins from
      normal and dystrophic rats in silver-stained gels. However, these two
      preparations showed significant differences with respect to their binding of the
      lectins, Lens culinaris (Lentil), Tetragonolobus purpurea (Lotus), and
      concanavalin A (Con A). In particular, a glycoprotein with a molecular weight of
      86 kD in the RPE apical membrane from normal rats bound Lentil, Lotus, and Con A,
      but in the membrane from dystrophic rats these binding sites were absent or
      significantly reduced. Another glycoprotein with a molecular weight of 175 kD was
      recognized by Lotus in the normal membrane preparation but not in the dystrophic
      RPE membrane preparation. Developmental studies show that these lectin-binding
      anomalies appear after postnatal day 11 and are, therefore, most likely
      coincident with eye opening in RCS rats. These results demonstrate that the RPE
      glycoproteins (86 and 175 kD) are significantly modified in dystrophic rats. The
      data also confirm previous observations that differences in the oligosaccharide
      chains, but not the polypeptide chains, of RPE membrane glycoproteins can be
      detected between normal and dystrophic rats. To the authors' knowledge, this is
      the first study to correlate developmentally regulated alterations in specific
      membrane-associated molecules in the RPE of dystrophic rats with the breakdown in
      phagocytosis that occurs in these rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1993584
TI  - Normal and dystrophic rat retinal pigment epithelia display different
      sensitivities to plant lectins.
AB  - Previous studies showed that cultured retinal pigment epithelial (RPE) cells from
      the Royal College of Surgeons (RCS) rat incorporate 50% less fucose into a number
      of cell-surface glycoproteins compared with controls. The cause of reduced fucose
      incorporation may be a generalized defect in glycoprotein processing in the RCS
      rat RPE. This hypothesis has been further explored by comparing the relative
      sensitivities of normal and dystrophic rat RPE to the toxicity of plant lectins
      of various specificities. Freshly isolated RPE cells from normal and dystrophic
      rats were cultured in the presence of increasing concentrations of lectin. For
      each lectin, the concentration at which less than 10% of the cells survived was
      determined. These tests showed that the dystrophic RPE cells were more sensitive
      to lectins that bound to core sugar moieties such as mannose and N
      acetylglucosamine; normal RPE cells were more sensitive to lectins which bound to
      the more terminally located sugars, galactose and N-acetylgalactosamine. Overall,
      the results suggest that decreased incorporation of fucose into the RCS RPE may
      be due to failure of the dystrophic RPE to add either N-acetylgalactosamine or
      galactose (to which fucose is subsequently added) to oligosaccharide structures.

PMID- 1993585
TI  - Human recombinant epidermal growth factor in experimental corneal wound healing.
AB  - Human recombinant epidermal growth factor (hEGF) was evaluated in various corneal
      wound healing models in the rabbit. Human EGF accelerated epithelial wound
      healing in corneal reepithelialization, anterior-keratectomy, and alkali-burn
      models at concentrations of 10-500 micrograms/ml given four times daily (qid). In
      the corneal reepithelialization model, 100 micrograms/ml of hEGF qid produced a
      45% increase in the wound-healing rate compared with control (0.13 versus 0.09
      mm/hr) with a similar response at 500 micrograms/ml qid. In the anterior
      keratectomy model, 500 micrograms/ml of hEGF qid accelerated healing by 40% (0.07
      versus 0.05 mm/hr), although the 100 micrograms/ml dose was not active in this
      model, and 1 microgram/ml of hEGF actually slowed the healing rate. In the alkali
      burn model, 10 and 100 micrograms/ml of hEGF qid for 32 days appeared to produce
      faster initial healing of the wound compared with control, although the wound
      recurred in both hEGF and control groups. These results suggest that hEGF may be
      helpful in some epithelial disorders in humans, although considerations of dose
      response and optimal dosing regimens must be addressed.

PMID- 1993586
TI  - Contact lens-induced edema in vitro. Pharmacology and metabolic considerations.
AB  - The effects of physiologic and pharmacologic manipulations on contact lens
      induced edema were studied. In isolated superfused rabbit corneas bathed in
      Ringer's solution and covered with large-diameter polymethylmethacrylate (PMMA)
      lenses, corneal swelling rates of 17-26 microns/hr (versus -5-5 microns/hr in
      paired controls) were observed. Neither the calcium antagonist diltiazem (10(-4)
      M), the glucocorticoid dexamethasone (10(-7) M), the glucose substitute fructose
      (20 mM), nor 0.5 mM adenosine and 0.3 mM reduced glutathione mitigated the edema.
      Lens-induced edema was 25 microns/hr in corneas bathed at pH 8.2 and decreased to
      9 microns/hr at pH 7.0. In corneas without lenses, however, decreasing the pH
      from 7.4-7.0 caused significant swelling (P less than 0.05). The pyruvate
      dehydrogenase stimulant sodium dichloroacetate (3.2 mM) on the tears side
      ameliorated the edema, and its congener, 3.2 mM 2-chloropropionate, was less
      effective. These latter agents are known to relieve lactic acidosis systemically
      and had no significant effect on corneas without lenses. In tissues bathed with
      20 mM lactate Ringer's, normal thickness was maintained in both control and PMMA
      treated corneas throughout the 3-hr period. These findings suggest that the
      contact lens-induced edema does not involve the acute cytotoxic mechanisms seen
      in severe tissue ischemia or hypoxia. The edema appears to result in part from
      acidosis but mainly from stromal lactate accumulation.

PMID- 1993587
TI  - Growth of acanthamoeba on human corneal epithelial cells and keratocytes in
      vitro.
AB  - Acanthamoebic keratitis, a potentially devastating infection usually associated
      with contact lens wear, has been recognized with increasing frequency in recent
      years. Once the Acanthamoeba organisms gain access to the human cornea, it is not
      clear which constituents of the corneal milieu provide a substrate for their
      growth. The growth of Acanthamoeba polyphaga was investigated on cultured
      monolayers of human corneal epithelial cells, stromal keratocytes, and stromal
      homogenate suspensions. Growth was determined through organism counts and
      observation of cytopathic effects on tissue culture dishes. Compared with tissue
      culture media controls, acanthamoebic growth was supported by cultured epithelial
      cells and keratocytes but not stromal homogenates. These results suggest that in
      acanthamoebic keratitis the organisms depend on the cellular components of the
      cornea as substrates for growth. This in vitro model may also provide further
      information on the pathogenesis of keratitis and a system for drug sensitivity
      testing.

PMID- 1993588
TI  - A reproducible method for injecting the mouse corneal stroma.
AB  - An improved delivery system for injecting the mouse corneal stroma was developed.
      This system incorporates the following features: a repeating dispenser that
      eliminates inaccuracies in depressing a syringe plunger, foot activation which
      frees both hands for manipulating the needle and permits constant observation of
      the injection site, and a flexible 30-cm, 32-gauge stainless steel needle with a
      30 degrees bevel and a locking hub that resists pulsation due to back pressure
      while permitting freedom of motion by the operator. These injections were done
      while observing the cornea with a vertically mounted slit lamp, ideally suited
      for examining and photographing the eyes of laboratory animals. The
      reproducibility of the new delivery system, expressed in terms of the signal-to
      noise ratio, was estimated and compared with that of a hand-held microsyringe by
      injecting a solution of radioactive chromium into the corneal stroma of A/J mice.
      The eyes were removed within 1 hr of injection, and the amount of chromium in
      each eye was determined in a gamma counter. The new delivery system had
      significantly (P less than 0.05) greater reproducibility than the hand-held
      syringe and could be calibrated to deliver up to 0.65 microliter to the mouse
      cornea.

PMID- 1993589
TI  - Murine models of Sjogren's syndrome. Evolution of the lacrimal gland inflammatory
      lesions.
AB  - Lacrimal gland inflammation develops in a number of autoimmune mice, including
      the MRL/Mp-lpr/lpr (MRL/lpr), MRL/Mp(-)+/+ (MRL/+), and NZB x NZW F1 hybrid
      (NZB/W) strains. The authors studied the evolution of this process, MRL/lpr mice
      had inflammatory lesions at 4 weeks old. The lesions had enlarged by 2 months and
      were fully developed by 4 to 5 months of age. In MRL/+ mice, 4-week-old mice had
      no lesions, although some focal inflammation was detectable at 3 months old.
      Significant abnormalities were present at 6 months, and persisted and increased
      throughout life, with all mice having extensive lesions at 18 months or older. In
      NZB/W mice, the authors detected no lesions until 6 months of age, and these
      lesions were fully developed in 9 months. Immunocytochemical profiles, of the
      cell types infiltrating the lacrimal gland, showed differences not only between
      the strains, but also in each strain as inflammation progressed. All three types
      of mice had L3T4+ T cells as the major lymphocyte component, although MRL/+ had
      significantly more Lyt 2+ T cells than the other strains. NZB/W mice had
      significantly more B cells than the two MRL substrains. In both NZB/W and MRL/+
      mice, there was a significant increase in the B cell population, and a decrease
      in the percentage of L3T4+ T cells. There was a significant decline in Lyt 2+ T
      suppressor/cytotoxic cells in both NZB/W and MRL/lpr mice. This last finding was
      consistent with the more rapid development of inflammation in these strains than
      in the MRL/+ mice, where Lyt 2+ T suppressor/cytotoxic cells persist. Together,
      these results indicate that the autoimmune response in murine models of Sjogren's
      syndrome is a dynamic, evolving process with strain-related changes in lymphocyte
      subsets.

PMID- 1993590
TI  - SDS-Minigel electrophoresis of human tears. Effect of sample treatment on protein
      patterns.
AB  - An automated Minigel electrophoresis system (PhastSystem, Pharmacia, Uppsala,
      Sweden) was tested for human tear protein analysis. Tear samples were treated
      under nonreducing or reducing conditions before sodium dodecyl sulphate polyacryl
      amide gel electrophoresis (SDS-PAGE). Micro-amounts of tears (2 microliters) were
      sufficient for analysis and separation and visualization of proteins were
      completed within 2 hr. Tear proteins were identified using purified control
      proteins and immunoblotting techniques, using antisera against immunoglobulin
      (Ig) A (alpha) heavy chains, Ig heavy and light chains, secretory components and
      lactoferrin. In nonreduced tears, lactoferrin (seen as a double band), serum
      albumin, tear-specific prealbumin (TSPA), and lysozyme were clearly separated.
      Secretory IgA (sIgA) was seen as a smear on top of the gel. Immunostaining also
      showed a major Ig light chain containing protein. After reduction, the protein
      profiles showed marked changes. In reduced tears, immunoglobulin heavy and light
      chains (molecular weight [MW]: 64 and 28 kD, respectively) were detected on the
      SDS-PAGE profile after immunostaining, and represented disulfide cleavage
      fragments, which originated from sIgA. Reduction resulted in the liberation of
      the secretory component piece (MW: 85 kD), which was found to co-migrate with the
      tear lactoferrin bands. Both lactoferrin and serum albumin acted as larger
      proteins on SDS-PAGE after reduction. The authors found that the two methods of
      sample treatment, before electrophoresis, resulted in marked differences on the
      electropherograms.

PMID- 1993591
TI  - Eyelid movements. Mechanisms and normal data.
AB  - This study provides a comprehensive description of upper eyelid movement in
      normal human subjects. Using the magnetic search coil technique to monitor lid
      position and modified skin electrodes to record orbicularis oculi
      electromyographic (EMG) activity, the authors found that the basic eyelid
      movements, blinks, and saccadic lid movements, can be uniquely and reliably
      characterized by their amplitude-maximum velocity relationships. The data show
      that similar increases in levator palpebrae activity produce the upward lid
      movements that accompany upward saccadic eye movements as well as the upward
      phase of a blink. The lid movements that accompany downward saccadic eye
      movements arise almost exclusively from the passive downward forces and
      relaxation of the levator palpebrae muscle. In contrast, active orbicularis oculi
      contraction and the passive downward forces act together to generate lid closure
      with a blink. These normative data and techniques provide the basis for the
      clinical analysis of lid motility by which abnormal lid movements can be compared
      with normal lid kinematics.

PMID- 1993592
TI  - Morphometry of the human lamina cribrosa surface.
AB  - The lamina cribrosa is a sieve-like perforation in the posterior part of the
      sclera, that allows passage of the retinal ganglion cell axons and central
      retinal vessels and preserves a pressure gradient between the intraocular and
      extraocular space. It has been termed the primary site of glaucomatous damage to
      the optic nerve. Using electron microscopy, the authors morphometrically
      evaluated the inner surface of the lamina cribosa in 40 normal human donor eyes.
      There were 14 men and 21 women with a mean age of 52 +/- 22 yr (10-82 yr). Mean
      single pore area (0.004 +/- 0.001 mm2) and summed pore area were significantly (P
      less than 0.05) larger and the ratio of summed pore area to lamina area was
      higher in the inferior and superior regions than in the temporal and nasal
      regions. The ratio decreased with increasing lamina cribrosa size. Count, size,
      form, and density of the pores were statistically independent of age, sex, side,
      and lamina cribrosa form. Pore count and summed pore area (mean: 0.92 +/- 0.22
      mm2) increased significantly with enlarging lamina cribrosa size. The area of the
      lamina cribrosa openings for passage of the central retinal vessels was
      independent of the lamina cribrosa size. The high ratio of summed pore area to
      lamina area and the large single pore area may be pathogenetically important for
      the increased glaucoma susceptibility in the inferior and superior disc regions.
      The lack of a correlation between lamina cribrosa size and the area of the lamina
      cribrosa openings for the retinal vessels may explain why central retinal vessel
      occlusions occur independently of optic disc size.

PMID- 1993593
TI  - Visual outcome in infants with cicatricial retinopathy of prematurity.
AB  - Monocular grating acuities of preterm infants with retinopathy of prematurity
      (ROP) were measured using a forced-choice preferential-looking (FPL) procedure.
      Eyes were independently graded by a retinal specialist and/or pediatric
      ophthalmologist and assigned to anatomic outcome categories on the basis of
      cicatricial residua of ROP. Eyes assigned to the normal/regressed and peripheral
      retinal changes categories (n = 120) had normal posterior poles. The authors
      found that grating acuities in this group were slightly lower than those of age
      matched healthy full-term infants, even when infants with amblyogenic or
      neurologic conditions were eliminated from the analysis. Grating acuity of eyes
      assigned to the macular ectopia, macular fold, partial detachment, or total
      detachment outcome categories (n = 60) had abnormal posterior poles, and grating
      acuity of these eyes was significantly related to anatomic outcome category (P
      less than 0.001). Follow-up data from subsets of eyes at 6 months, 12 months, or
      2-5 yr after the initial acuity test suggest that early FPL acuity tests may be
      predictive of long-term functional outcome (r = 0.75-0.87).

PMID- 1993594
TI  - Interrelations between measures of visual acuity and parameters of eye movement
      in congenital nystagmus.
AB  - The authors assessed relationships between visual acuity and the amplitude,
      frequency, intensity, and duration of foveation periods in a retrospective study
      of 32 patients. Twenty-four patients had congenital idiopathic nystagmus, and
      eight patients had nystagmus and albinism. Visual acuity was determined for
      Landolt ring optotypes and, as the extrapolated high-frequency cutoff of the
      contrast sensitivity function, for horizontal and vertical gratings. No
      significant correlation existed between acuity and any measured eye movement
      parameter; however, optotype acuity was related to the magnitude of astigmatic
      refractive correction, both in patients with idiopathic nystagmus and in albinos.
      In a subgroup of patients with idiopathic nystagmus whose astigmatic refractive
      error was -1.50 D or less, nystagmus intensity (amplitude x frequency) correlated
      significantly with acuity for optotypes (r = 0.71), but not for gratings.
      Although resolution for vertical gratings was correlated with astigmatic
      refractive correction, the ratio of resolution for gratings parallel and
      orthogonal to the meridian of nystagmus was not. Thus, the belief that poorer
      acuity in patients with substantial astigmatism is attributable to an optically
      induced meridional amblyopia is supported only partly by these results. The
      authors concluded that among patients with congenital nystagmus, the influence of
      eye motion on visual acuity is not readily predicted either from the parameters
      of nystagmus that they evaluated or from the comparison of resolution for
      horizontal and vertical gratings.

PMID- 1993595
TI  - Clinical grading and the effects of scaling.
AB  - In clinical practice, there has been a need to grade the magnitude or the
      severity of the functions and qualities that are assessed in the examination. It
      is popular to use a four-step grading scale to categorize the severity of
      clinical findings. The authors discuss clinical grading scales and their
      influence on the clinician's ability to detect change. These principles have been
      applied to grades or measures derived from either objective measuring
      instruments, subjective tests, or techniques in which the clinician makes
      subjective judgments. A hypothetical data set was used to show the problems
      associated with using grading scales that are too coarse. The authors presented a
      mathematic model that helps to estimate the benefits of using use of a finer
      scale. Data were presented from two separate studies, one on visual acuity
      measurement and the other on grading nuclear opacity, to show the advantages of
      using finer scales to enhance the sensitivity of clinical measurement. High
      levels of concordance between independent observations indicated that the grading
      scale was too coarse and that these scales needlessly reduced the clinician's
      ability to detect change in the parameter being assessed. For moderate
      sensitivity, the size of the scale increments should not exceed one standard
      deviation of the discrepancy so that the concordance of paired comparisons would
      not exceed 37%. For fine clinical sensitivity, the size of the scale increments
      should not exceed one third of the standard deviation of the discrepancy, in
      which case the concordance of paired comparisons would not exceed 13%. The theory
      and evidence presented here could prompt re-evaluations of common methods of
      clinical grading.

PMID- 1993596
TI  - Flow cytometry measurements of the DNA content of corneal epithelial cells during
      wound healing.
AB  - This study presents the first application of flow cytometry (FCM) techniques to
      the assessment of cell cycle dynamics in the corneal epithelium after
      experimental wounding. Anterior keratectomies 6 mm in diameter were created in
      the central corneas of albino rabbits. The authors sampled the epithelial tissue
      obtained outside the wound at 12-hr intervals until wound closure at 72 hr.
      Regenerated epithelium from the surface of the wounded area was collected at 78
      hr. The percentages of nuclei in the G0/G1 (growth), S (DNA synthesis), and G2/M
      (tetraploid/mitosis) phases were determined by FCM. An increase in the percentage
      of nuclei in the G2/M phase at 36 hr was seen, compared with cell populations in
      samples from unwounded control corneas. The authors found an increase in mitotic
      activity in the corneal epithelium during the period of cell migration before
      wound closure.

PMID- 1993597
TI  - Anomalous motion VEPs in infants and in infantile esotropia.
AB  - Visual evoked potentials (VEPs) were recorded monocularly in response to vertical
      gratings that underwent oscillatory apparent motion at a temporal frequency of 10
      Hz. In normal infants 6 months or younger and in patients with a history of
      constant strabismus onset before 6 months of age, the oscillatory motion VEP
      contains a prominent first harmonic component that is temporally 180 degrees out
      of phase in the two eyes. This pattern is not seen in normal adults and is
      consistent with the presence of a nasalward/temporalward asymmetry of cortical
      responsiveness in infants and in patients with early onset strabismus.

PMID- 1993598
TI  - Health visiting under scrutiny.

PMID- 1993599
TI  - Access to health care for black people.

PMID- 1993600
TI  - School nursing: setting up a school first-aid club.

PMID- 1993601
TI  - Health visiting in rural Gambia.

PMID- 1993602
TI  - Health promotion: working together for Project health.

PMID- 1993603
TI  - Poll tax: what happens to non-payers.

PMID- 1993604
TI  - Maternity leave: the battle of the bulge.

PMID- 1993605
TI  - Asbestos still a killer.

PMID- 1993606
TI  - Asthma: encouraging a better lifestyle.

PMID- 1993607
TI  - HIV/AIDS: call for family centered services.

PMID- 1993608
TI  - When a child dies tragically.

PMID- 1993609
TI  - NHS reforms: what will we find at the market?

PMID- 1993610
TI  - Surviving home healthcare: one agency's experience.
AB  - Too often, home health agencies are narrow and territorial in their outlook.
      Ideas need to be sought, developed, and acted upon after all the risks have been
      weighed. If home health agencies don't manage themselves as businesses, then they
      will be out of business and not able to serve anyone.

PMID- 1993611
TI  - Planning for successful home healthcare.
AB  - Finally, a nursing care plan that really works! This system helps the nurse
      provide the best care possible while assuring that the patient's goals are being
      met. Documentation is improved but less time is spent writing care plans and
      prolific nurse's notes.

PMID- 1993612
TI  - Wanted!

PMID- 1993613
TI  - But is it nursing?

PMID- 1993615
TI  - The legalities of home care. Advance directives after Cruzan: the time is now.

PMID- 1993614
TI  - Chemical addiction in nurses: a solvable problem for the home health industry.

PMID- 1993616
TI  - Medicare and the nurse. The peer review organization (PRO).
AB  - The PRO process is just one of the many reviews that HHAs are subjected to at any
      given time. On a practical level, HHA should incorporate PRO criteria and GQSs
      into its QA program. At present, there is no mechanism in place for denial of
      payment for substandard care, although proposed regulations were published in the
      January 18, 1989 Federal Register. Medicare certification, and therefore payment,
      could be lost if the facility or HHA were sanctioned. The Medicare law requires
      PROs to coordinate their activities with other review organizations. HCFA,
      however, has not established procedures for providing reports from fiscal
      intermediaries and PROs to the state survey agencies or coordinating state
      surveys with PRO reviews. HHAs should have structure and process criteria in
      place (either manual or computerized) to identify selected records for review.
      This enables the agency to monitor its internal quality assurance activities so
      that it has confidence that the GQSs will be met when reviewed by external
      agencies, including the PRO. This internal monitoring will also enable the agency
      to document patient outcomes. This is an important aspect of the evaluation
      process, since the emphasis of certification and accreditation programs and site
      visits will be focused on patient outcomes in the 1990s.

PMID- 1993617
TI  - Strategies for financing home healthcare.
AB  - Insurance coverage for home healthcare is often inadequate, especially in chronic
      or terminal illnesses. As a result, your patients or families may be faced with
      catastrophic medical expenses and find it necessary to explore creative
      approaches for financing home care.

PMID- 1993618
TI  - Competition and continuity of care in home health nursing.
AB  - As the home health field grows, efforts directed toward improved communication in
      all areas must be developed. This will assure quality patient care and increased
      respect for the nurses involved in the practice of home healthcare nursing.

PMID- 1993619
TI  - Improvements observed in care and outcome in carcinoma of the larynx.
AB  - The 1978 Patterns of Care Studies (PCS) survey of carcinoma of the larynx
      reviewed the process (pre-treatment evaluation and treatment) and outcome of 521
      patients. When compared to results from the 1973 PCS survey, several important
      changes have been observed. The use of surgery in conjunction with radiation
      therapy (RT) increased in Stage III cases from less than 30% to greater than 60%
      and in Stage IV cases from 48% to greater than 70%. This change in therapy was
      associated with a decline in locoregional failure in this patient group. Among
      Stage I and II supra- and subglottic carcinomas, an improvement in 3-year local
      tumor control (Stage I: 78 to 100% and Stage II: 54 to 74%) and overall freedom
      from recurrence (Stage I: 78 to 100% and Stage II: 45 to 73%) was seen over this
      5-year period with no identifiable change in process for this subgroup. Also
      noted was an improvement in the freedom from recurrence rate for Stage III and IV
      patients receiving treatment at facilities with low process scores. The 1978 PCS
      survey confirmed the presence of superior patient outcome in several subgroups
      and the relationship of this improvement to patient process.

PMID- 1993620
TI  - Compensation in three-dimensional non-coplanar treatment planning.
AB  - This paper presents a technique for producing uniform dose distributions within
      the target volume with non-coplanar field arrangements. The method is based upon
      the principle used for producing homogeneous dose distributions for a pair of
      fields in two dimensions, namely, that if the isodose distributions for the
      fields are made parallel to one another, the combined dose distribution will be
      uniform. For the three-dimensional non-coplanar case, homogeneous target dose
      distributions are obtained by designing field modifiers which produce a uniform
      dose distribution on the perpendicular bisector plane for each pair of fields. It
      is demonstrated that for three non-coplanar fields irradiating a spherical
      phantom with spherical target volumes, the target dose distribution will be
      homogeneous for any arbitrary non-coplanar field arrangement. Furthermore, this
      technique can be extended to any number of fields. Therefore, target dose
      distributions for non-coplanar plans can be as homogeneous as the coplanar case.
      An example of the application of the method to the treatment of rectal carcinoma
      with non-coplanar fields is given. Furthermore, it is demonstrated that the
      therapeutic ratio is improved over traditional methods for this clinical example.

PMID- 1993621
TI  - Elapsed treatment days--a critical item for radiotherapy quality control review
      in head and neck trials: RTOG report.
AB  - For all randomized trials since 1978, the Radiation Therapy Oncology Group has
      required the study chairman for radiation therapy to review the treatment given
      to each patient. The chairman scores the compliance of the treatment borders,
      total dose, fraction, and total elapsed time relative to the protocol
      prescription at the primary site, regional nodes, and any critical structure. The
      individual parameters are then considered together to derive an "overall"
      treatment score. For two RTOG head and neck studies in patients with moderately
      and very advanced carcinomas, the "overall" treatment was classified as
      unacceptable if the treatment at primary was scored unacceptable with respect to
      dose, fractionation, and field borders. However, prolonged elapsed treatment was
      not included. Analysis of these studies with 426 evaluable patients was performed
      to assess the relationship of unacceptable "overall" treatment compliance with
      outcome. Patients with prolonged treatment elapsed days (14 days beyond the
      protocol prescription) exhibited significantly poorer loco-regional control (13%
      vs. 27% at 3 years with p = .007) and absolute survival (13% vs. 26% at 3 years
      with p = .01). As a result, the criteria for unacceptable "overall" treatment
      were revised to include prolonged elapsed treatment days. Further multivariate
      analyses showed the revised criteria identified patients with significantly
      poorer loco-regional control and absolute survival even after adjusting for other
      prognostic factors.

PMID- 1993622
TI  - Quantitative assessment of interstitial implants.
AB  - Quantitative assessment of interstitial implants is proposed using volume versus
      dose curves and four well-defined dosimetric parameters. The volume versus dose
      curves, both differential and cumulative, provide quantitative data on the
      volumes of tissues irradiated to different doses. They also offer a qualitative
      assessment of the variations in dose delivery. The dose nonuniformity ratio (DNR)
      quantitatively determines the degree of dose nonuniformity specific to the
      implant configuration. The dose rate at which the DNR shows a minimum value, if
      selected as the treatment dose rate, gives an optimized dose distribution. The
      three volumetric irradiation indices are formulated with respect to a well
      defined target volume. They offer quantitative data on the extent to which the
      implant delivers the prescribed dose to the target volume. These dosimetric
      parameters determine the degree of coverage of the target volume, dose
      homogeneity within the target volume, and irradiation of tissues outside the
      target volume. The method of quantitative assessment is demonstrated using, as
      examples, an ideal Ir-192 double-plane implant and an actual clinical Ir-192
      double-plane breast implant.

PMID- 1993623
TI  - Conformal static field therapy for low volume low grade prostate cancer with
      rigid immobilization.
AB  - The ability to improve existing standards of treating prostate cancer was
      investigated. To deliver a homogenous dose to the prostate with as little normal
      tissue margin as practical, seven patients with low volume carcinoma of the
      prostate were immobilized with alpha cradle body casts prior to using a CT-based
      3D treatment planning system and beam's eye view (BEV) template. All patients had
      clinical Stage B-1 prostate cancer of favorable histologic differentiation
      (Gleason Score 2-5). A four field box technique was used, each beam having a
      single customized cerrobend block cut-out conforming to the exact contour of the
      prostate. To assess the accuracy of this process, daily port films were taken for
      5 consecutive days and compared to a matched control group who were treated in a
      similar fashion, but were not casted. Dose volume histograms illustrate an
      average of 14% of bladder dose and 14% of rectal dose that can be eliminated
      using this technique when compared to field sizes and block placement in our
      previous technique. Daily setup variation was markedly improved using the cast,
      with a median daily variation of 1 mm as compared to 3 mm without the cast. The
      average range of movement for each of the seven casted patients was 3.3 mm as
      compared to 8 mm for the seven uncasted patients. Immobilization eliminated the
      worst 10% of all daily positioning errors. Using CT treatment planning with the
      patient casted and BEV allows for precise block placement with the prostate gland
      in its proper orientation during daily treatment. With improved immobilization
      and precise localization of the prostate gland, margins around the target can be
      made significantly smaller, and this may translate into a decrease in acute
      and/or late complications.

PMID- 1993624
TI  - A review of hypoxic cell radiosensitization.
AB  - Despite an enormous laboratory and clinical effort, advance in patient care has
      not yet been achieved by hypoxic cell radiosensitization. The reasons for this
      are considered and suggestions made as to the future direction of work in this
      important field.

PMID- 1993625
TI  - Techniques in the radiation treatment of carcinoma of the uterine cervix.

PMID- 1993626
TI  - One vs two or more brachytherapy applications in cervical cancer.

PMID- 1993627
TI  - Conditions for the equivalence of continuous to pulsed low dose rate
      brachytherapy.
AB  - Low dose rate interstitial brachytherapy is extremely useful for those tumors
      that are accessible for an implant, while the introduction of remote afterloaders
      has eliminated exposure to nursing personnel. Currently, such machines require an
      inventory of many sources which are loaded into catheters implanted in the tumor
      and kept in place during treatment. A significant simplification of such machines
      would be possible in a pulsed mode, with a single source moving under computer
      control through the catheters. Assuming that the treatment time and average dose
      rate are kept unchanged, the question addressed is to find those combinations of
      radiation pulse widths and frequencies that would be functionally equivalent to a
      continuous irradiation. The linear-quadratic formalism was used to reanalyze
      published low dose-rate studies on cells of human origin to obtain 36 parameter
      sets [alpha, beta, T1/2], where T1/2 is the half time for sublethal damage
      repair. These data are consistent with those for human tumors. For each parameter
      set, those combinations of pulse width and frequency were calculated that would
      yield a functionally equivalent cell survival. For a regimen of 30 Gy in 60 hr, a
      pulse width of 10 min with a period between pulses of 1 hr would be appropriate
      for all the cell lines considered. Similar results were found for other possible
      time/dose combinations. For late effects, a 1-hr period between 10-min pulses
      might produce up to a 2% increase in late-effect probability, which is probably
      acceptable for the small volumes irradiated in interstitial brachytherapy.

PMID- 1993628
TI  - Randomized study of preoperative versus postoperative radiation therapy in
      advanced head and neck carcinoma: long-term follow-up of RTOG study 73-03.
AB  - This is a report of a 10-year median follow-up of a randomized, prospective study
      investigating the optimal sequencing of radiation therapy (RT) in relation to
      surgery for operable advanced head and neck cancer. In May 1973, the Radiation
      Therapy Oncology Group (RTOG) began a Phase III study of preoperative radiation
      therapy (50.0 Gy) versus postoperative radiation therapy (60.0 Gy) for
      supraglottic larynx and hypopharynx primaries. Of 277 evaluable patients,
      duration of follow-up is 9-15 years, with 7.6% patients lost to follow-up before
      7 years. Loco-regional control was significantly better for 141 postoperative
      radiation therapy patients than for 136 preoperative radiation therapy patients
      (p = 0.04), but absolute survival was not affected (p = 0.15). When the analysis
      was restricted to supraglottic larynx primaries (60 postoperative radiation
      therapy patients versus 58 preoperative radiation therapy patients), the
      difference for loco-regional control was highly significant (p = .007), but not
      for survival (p = 0.18). In considering only supraglottic larynx, 78% of loco
      regional failures occurred in the first 2 years. Thirty-one percent (18/58) of
      preoperative patients failed locally within 2 years versus 18% (11/60) of
      postoperative patients. After 2 years, distant metastases and second primaries
      became the predominant failure pattern, especially in postoperative radiation
      therapy patients. This shift in the late failure pattern along with the increased
      number of unrelated deaths negated any advantage in absolute survival for
      postoperative radiation therapy patients. The rates of severe surgical and
      radiation therapy complications were similar between the two arms. Because of an
      increased incidence of late distant metastases and secondary primaries,
      additional therapeutic intervention is required beyond surgery and postoperative
      irradiation to impact significantly upon survival.

PMID- 1993629
TI  - High dose preoperative irradiation for cancer of the rectum, 1976-1988.
AB  - Two hundred twenty patients with adenocarcinoma of the rectum have been treated
      in a program using high dose (greater than 4000 cGy) preoperative irradiation
      followed by radical surgical resection. The patients were staged on the basis of
      pretreatment clinical mobility of the cancers. Seventy-four patients had mobile
      cancers, 49 had partial fixation (tethered), 85 patients had total tumor
      fixation, and 12 patients had a frozen pelvis (unresectable). Patients were
      treated with high energy photons using a four field box technique with total
      doses ranging from 4000 to 6000 cGy. The overall incidence of local recurrence
      was 15% (32/220). Patients with fixed and unresectable tumors had a higher
      incidence of local recurrence, 20% (21/97) as compared with patients with mobile
      and partially fixed tumors, 10% (13/123). Local recurrence by pathological stage
      of disease was 6% for patients with Stages O, A, B1 versus 20% for patients with
      Stages B2 and C cancer. Overall 5-year survival of the total group was 67%. The 5
      year survival by clinical stages of disease was 87% for mobile tumors, 74% for
      partially fixed tumors, 70% for fixed tumors, and 22% for the unresectable group.
      The 5-year survival by pathological stages of disease was 90% for those with
      Stage O, A, B1 and 71, 75, and 47%, respectively, for Stages B2, C1, and C2
      disease.

PMID- 1993630
TI  - Prognostic factors in patients with early stage non-Hodgkin's lymphomas of the
      head and neck treated with definitive irradiation.
AB  - Between 1974 and 1989, 58 patients with clinical Stages I and II non-Hodgkin's
      lymphomas of the head and neck were treated with radiation at the Fox Chase
      Cancer Center. Forty-one treated with radiotherapy alone form the basis for this
      retrospective analysis of outcome and prognostic factors. With a mean radiation
      dose of 4400 cGy, the 5-year actuarial local control rate is 92%. Only one
      patient failed within an irradiated field. The 5-year actuarial survival and
      relapse-free survival rates are 85% and 54%, respectively. In a univariate
      analysis, poor survival was significantly correlated with involvement of
      Waldeyer's ring, postoperative tumor size greater than 3 cm, and greater than two
      involved lymph nodes and extranodal sites (p less than 0.02). No such
      correlations were seen for stage, histologic grade, the presence of extranodal
      disease, or any of the other parameters that were examined. Relapse free survival
      was significantly correlated only with the total of the number of involved nodes
      and extranodal sites. Patients with one or two involved nodes and sites had a 68%
      chance of remaining disease-free at 5 years compared to 0% for patients with
      greater than two (p = .02). Again, significant trends were not seen for the other
      parameters analyzed. These data demonstrate excellent local control, survival,
      and relapse-free survival using radiation alone with doses of 3000-5000 cGy. In
      our group of clinically staged patients preselected for treatment with radiation
      alone, the total of the number of involved nodes and extranodal sites,
      involvement of Waldeyer's ring, and tumor size after resection correlated
      strongly with relapse-free survival and overall survival. In patients with early
      stage non-Hodgkin's lymphomas of the head and neck, initial management with
      external beam radiotherapy should be considered in particular for those with one
      or two involved nodes and extranodal sites that are less than 3 cm following
      resection and that do not involve Waldeyer's ring.

PMID- 1993631
TI  - A randomized phase III protocol for the evaluation of misonidazole combined with
      radiation in the treatment of patients with brain metastases (RTOG-7916).
AB  - From 1979 through July 1983, 859 patients were enrolled in a Phase III RTOG
      Protocol (7916) evaluating the role of Misonidazole combined with radiation in
      the treatment of brain metastasis. Patients were randomized to one of four
      treatment arms (3.0 Gy x 10 fractions with or without 1 g/m2 of Misonidazole
      [total 10 g/m2] versus 5.0 Gy x 6 fractions with or without 2 g/m2 of
      Misonidazole) [total 12 g/m2]. Among the 779 analyzable cases, 63% had a lung
      primary and 12% had breast. Of the histologic types, 43% were adenocarcinoma and
      24% were squamous cell. Seventy-eight percent had a Karnofsky of greater than 70.
      Of the 779 cases, 773 are dead (99%). Median survival is 3.9 months, with 60%
      alive at 3 months, 35% at 6 months, and 15% at 1 year. Survival was evaluated by
      treatment arm, Misonidazole status, and fractionation scheme; none showed any
      statistical significance. Favorable prognostic factors were assessed (age less
      than 60, Karnofsky of 70-100, controlled primary and brain metastasis only) in
      each treatment arm and no difference was found. Brain metastasis was cause of
      death in 1/3, and 19-33% of patients were retreated. Because up to 1/3 of the
      patients in this study died secondary to uncontrolled brain metastasis,
      improvement in local control remains an important goal. Until proven otherwise,
      the treatment of choice for the majority of patients still remains a conventional
      palliative course of 3.0 Gy x 10 fractions.

PMID- 1993632
TI  - Effect of external pH on heat sensitization by local anesthetics.
AB  - The sensitization of asynchronous Chinese hamster ovary (CHO) cells to 43 degrees
      C by procaine, lidocaine, and tetracaine was examined, with the pH of the medium
      carefully controlled at approximately pH7 and 8. Thermal enhancement factors for
      43 degrees C were calculated for the surviving fraction of 0.01. The thermal
      enhancement factors of the local anesthetics were increased at approximately pH8
      by factors of 2-12, depending on the local anesthetic and its concentration. The
      concentration of the uncharged free base form of the local anesthetic in the
      culture medium correlated positively with the thermal enhancement factors of each
      local anesthetic and in a near linear fashion with the thermal enhancement
      factors for procaine. However, the concentration of the cationic form of the
      local anesthetics in the growth medium did not correlate with heat sensitization.
      We conclude that the ability of local anesthetics to sensitize cells to heat
      killing is dramatically influenced by the extracellular pH, with increased
      sensitization at the more basic pH's. Secondly, it is the extracellular
      concentration of the free base form of the local anesthetics that correlates with
      heat sensitization.

PMID- 1993634
TI  - Patterns and sites of failure in cervix cancer treated in the U.S.A. in 1978.
AB  - Patterns of Care Study (PCS) conducted the second survey of carcinoma of the
      cervix in 1978. The data of this survey are derived from 565 patient
      questionnaires completed from 120 randomly selected facilities. Through these
      surveys PCS has set out to establish a profile of the practice of radiation
      therapy in the United States as well as determine the survival, local control
      rates, patterns of recurrence, complications, and relationship of these events
      with dose. This study deals with the patterns and sites of failure and
      relationship with dose to the paracentral and lateral points previously defined.
      The breakdown of patients according to the stage was as follows: Stage I = 203,
      Stage II = 243, Stage III = 115, undertermined = 4. Twenty-three percent of the
      patients failed within the field of irradiation, whereas 9% failed outside of the
      irradiated field. The infield failure rate increased as a function of stage from
      9% in Stage I to 23% in Stage II and 48% in Stage III. Distant metastasis was the
      first site of failure in 4% of patients with Stage I, 7% for Stage II, 9% for
      Stage III, and 6% for the entire group. The cervix and vagina were the first site
      of recurrence in 20% of the patients. The cervical/vaginal recurrence rate
      increased as a function of stage from 7% in Stage I to 21% in Stage II, and 37%
      in Stage III. An analysis of the cervical/vaginal recurrences as a function of
      the average total dose to the paracentral points showed a decreased recurrence
      rate as a function of dose within the range of less than 6500 to 7999 cGy. The
      recurrence rate at 4 years decreased from 34% with a dose of less than 6500 cGy
      to 14% with a dose of 7500-7999 cGy. Above this dose level, this correlation of
      dose with recurrence was not observed. This correlation was also absent when the
      patients were studied according to the stage of the disease. The relationship of
      parametrial/sidewall failure and average dose to the lateral point was studied
      also, but no correlation was found except for patients with Stage III disease.
      The disease-free survival was studied for the entire group of patients and for
      the different stages as a function of average paracentral dose: less than 7500
      cGy, 7500 to 8500 cGy, and greater than 8500 cGy. The disease-free survival was
      lower for the patients in the less than 7500 cGy group.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 1993633
TI  - Phase I/II study, combination of radiotherapy and hyperthermia in patients with
      deep-seated malignant tumors: report of a pilot study by the Radiation Therapy
      Oncology Group.
AB  - This is a report of a Phase I/II study activated in March 1984 and completed in
      October 1988 by the Radiation Therapy Oncology Group on the feasibility/toxicity
      of hyperthermia in patients with deep-seated malignant tumors. The main objective
      of this study was to evaluate the morbidity of regional hyperthermia (systemic
      and regional, acute and late effects); a secondary objective was to evaluate
      tumor response to combined irradiation and regional hyperthermia. A total of 54
      patients with locally advanced abdominal or pelvic malignancy were accrued to
      this study; 42% were male and 58% female. Seventy-five of the patients had pelvic
      tumors and 25% abdominal tumors. Acute toxicities included grade 4 in three
      patients (1 cutaneous, 1 infection and 1 chemical peritonitis) one grade 3
      (skin), and 12 grade 2 toxicities (6 skin and 6 gastrointestinal). With regard to
      late toxicities, grade 4 was noted in one patient (skin), grade 3 (GI) in one,
      and grade 2 (skin, peripheral neuropathy) in six patients. The prescribed course
      of hyperthermia was completed in 17 (32%) of patients. In 36 patients (68%) the
      course of hyperthermia was terminated, primarily because of patient discomfort.
      Tumor response was assessed by physical examination or radiological studies. Of
      44 patients evaluable for response, there were 17 (39%) complete responses and 6
      (14%) partial responders. Significant technical problems in heat delivery and
      thermometry remain.

PMID- 1993635
TI  - Tumor and treatment factors improving outcome in stage III-B cervix cancer.
AB  - This report reviews 271 patients with Stage III-B squamous cell cancer of the
      uterine cervix from three national surveys conducted by the Patterns of Care
      Study. A progressive increase in local control and survival is seen among the
      three surveys which parallels a progressive increase in paracentral (point A)
      dose and use of intracavitary treatment. Multivariate analysis reveals extent of
      pelvic disease (unilateral sidewall vs. bilateral sidewall vs. lower 1/3 vagina)
      and use of intracavitary treatment to be the only significant tumor and treatment
      factors associated with local control and survival. With aggressive radiotherapy,
      local control rates exceeding 65% and survival of 50% at 4 years can be
      anticipated at the expense of a small increase in complications.

PMID- 1993636
TI  - Long-term follow-up of chronic depression treated with imipramine.
AB  - A long-term follow-up assessment was conducted in 25 chronically depressed
      patients who had participated in a 6-week trial of imipramine to determine if
      imipramine responders would sustain a more favorable long-term outcome than
      nonresponders or noncompleters. Imipramine responders tended to remain on
      imipramine treatment throughout the follow-up interval and had a significantly
      better outcome. Eighty-nine percent of the imipramine responders met the criteria
      for recovery at follow-up compared with 31% in the comparison groups. Imipramine
      responders also fared significantly better at follow-up on measures of
      depression, global severity of illness, and social/vocational functioning. The
      results supported a more favorable long-term outcome in chronic depression
      patients who had responded to imipramine and suggest that maintenance therapy may
      be indicated and effective for this disorder.

PMID- 1993637
TI  - Successful antidepressant treatment of nonparaphilic sexual addictions and
      paraphilias in men.
AB  - Nine of 10 consecutively evaluated men with DSM-III-R nonparaphilic sexual
      addictions or paraphilias noted improvement in sexual behaviors and depressive
      symptomatology while treated with fluoxetine, imipramine, or lithium. Depression
      was measured by means of the Inventory to Diagnose Depression. Sexual behavior
      was assessed in two dimensions, nonconventional interest and intensified desire,
      as measured by total sexual outlet. The author conceptualizes these behaviors as
      sexual dysregulation disorders associated with a primary mood disorder.

PMID- 1993638
TI  - The role of serotonin in sexual dysfunction: fluoxetine-associated orgasm
      dysfunction.
AB  - Iatrogenic sexual dysfunction has been associated with many pharmacologic agents.
      The authors report 6 cases of orgasm dysfunction associated with the use of
      fluorxetine in 77 depressed outpatients. Fluoxetine is a novel antidepressant
      known to block the reuptake of serotonin with little effect on other
      neurotransmitter systems. Because fluoxetine has a specific mechanism of action,
      it serves as a useful model to hypothesize about potential mechanisms of drug
      induced sexual dysfunction. The possible effects of serotonin on central, spinal,
      and peripheral anatomical areas are discussed in relation to drug-induced sexual
      dysfunction.

PMID- 1993639
TI  - Double-blind, placebo-controlled comparison of clonazepam and alprazolam for
      panic disorder.
AB  - To test the reported antipanic efficacy of clonazepam, the authors randomized 72
      subjects with panic disorder to 6 weeks of treatment with either alprazolam,
      clonazepam, or placebo. Endpoint analysis demonstrated a significant beneficial
      effect of both active treatments, but not placebo treatment, on the frequency of
      panic attacks, overall phobia ratings, and the extent of disability. Comparison
      of the two active treatments revealed no significant differences and no
      consistent tendency for one agent to be favored over another, although power to
      detect small differences was limited. Sedation and ataxia were the most common
      side effects reported, but these effects were mild and transient and did not
      interfere with treatment outcome. The results of this double-blind, placebo
      controlled trial are consistent with previous reports of clonazepam's antipanic
      efficacy.

PMID- 1993640
TI  - Dose response effects of zolpidem in normal geriatric subjects.
AB  - The dose-related hypnotic effects and effects on memory, performance, and daytime
      alertness of zolpidem 5, 10, 15, and 20 mg were compared with those of placebo in
      30 elderly non-insomniac volunteers in a randomized, placebo-controlled, three
      period crossover study. Subjects were randomized into two groups and received
      either placebo, zolpidem 5 mg, or zolpidem 15 mg or placebo, zolpidem 10 mg, or
      zolpidem 20 mg for 2 consecutive nights followed by 1 night of placebo during the
      same 3 nights of 3 consecutive weeks. Polysomnographic results showed
      statistically significant decreases in sleep latency and increases in sleep
      efficiency at all doses. Subjective reports also showed improved sleep latency,
      total sleep time, and sleep quality. REM percent was slightly decreased at doses
      of 10 and 20 mg. No consistent effects on memory or performance were observed,
      and the Multiple Sleep Latency Test showed no effects on daytime sleepines. There
      was no objective evidence of rebound insomnia upon drug discontinuation.

PMID- 1993641
TI  - De Clerambault's syndrome in sexually experienced women.
AB  - De Clerambault's syndrome is said to usually occur in heterosexual women with
      little overt sexual experience. The authors present five cases of women with
      considerable sexual experience including, in some instances, homosexual activity
      and discuss their diagnosis of De Clerambault's syndrome in the context of what
      has been reported in the literature.

PMID- 1993643
TI  - Fluoxetine treatment of trichotillomania.

PMID- 1993642
TI  - Strategies for fluoxetine-MAOI combination therapy.

PMID- 1993644
TI  - Lifetime history of panic attacks and epilepsy: an association from a general
      population survey.

PMID- 1993645
TI  - New onset Raynaud's phenomenon in a schizophrenic patient.

PMID- 1993646
TI  - The interleukin-2 receptor.

PMID- 1993647
TI  - Phosphorylation of the proto-oncogene product eukaryotic initiation factor 4E is
      a common cellular response to tumor necrosis factor.
AB  - The initiation of mRNA translation is regulated by the reversible phosphorylation
      of several initiation factors. We report here that tumor necrosis factor-alpha
      (TNF) rapidly stimulates phosphorylation of one such factor, an mRNA cap binding
      protein, in several cell types which are important in vitro models of TNF action.
      This protein has been purified, sequenced, and identified as the proto-oncogene
      product eukaryotic initiation factor 4E. These data show that phosphorylation of
      a key component of the cellular translational machinery is a common early event
      in the various actions of TNF in diverse cell types.

PMID- 1993648
TI  - Regulation of cholesterol 7 alpha-hydroxylase by hepatic 7 alpha-hydroxylated
      bile acid flux and newly synthesized cholesterol supply.
AB  - We measured hepatic cholesterol 7 alpha-hydroxylase activity, mass, and catalytic
      efficiency (activity/unit mass) in bile fistula rats infused intraduodenally with
      taurocholate and its 7 beta-hydroxy epimer, tauroursocholate, with or without
      mevalonolactone to supply newly synthesized cholesterol. Enzyme activity was
      measured by an isotope incorporation assay and enzyme mass by densitometric
      scanning of immunoblots using rabbit anti-rat liver cholesterol 7 alpha
      hydroxylase antisera. Cholesterol 7 alpha-hydroxylase activity increased 6-fold,
      enzyme mass 34%, and catalytic efficiency 5-fold after interruption of the
      enterohepatic circulation for 48 h. When taurocholate was infused to the bile
      acid-depleted animals at a rate equivalent to the hepatic bile acid flux (27
      mumol/100-g rat/h), cholesterol 7 alpha-hydroxylase activity and enzyme mass
      declined 60 and 61%, respectively. Tauroursocholate did not significantly
      decrease cholesterol 7 alpha-hydroxylase activity, mass and catalytic efficiency.
      The administration of mevalonolactone, which is converted to cholesterol,
      modestly increased cholesterol 7 alpha-hydroxylase activity and enzyme mass in
      the bile acid-depleted rats. However, when taurocholate was infused together with
      mevalonolactone, cholesterol 7 alpha-hydroxylase activity and catalytic
      efficiency were markedly depressed while enzyme mass did not change as compared
      with bile acid-depleted rats. These results show that (a) hepatic bile acid
      depletion increases bile acid synthesis mainly by activating cholesterol 7 alpha
      hydroxylase with only a small rise in enzyme mass, (b) replacement with
      taurocholate for 24 h decreases both cholesterol 7 alpha-hydroxylase activity and
      mass proportionally, (c) when cholesterol is available (mevalonolactone
      supplementation), the infusion of taurocholate results in the formation of a
      catalytically less active cholesterol 7 alpha-hydroxylase, and (d)
      tauroursocholate, the 7 beta-hydroxy epimer of taurocholate, does not inhibit
      cholesterol 7 alpha-hydroxylase. Thus, bile acid synthesis is modulated by the
      catalytic efficiency and mass of cholesterol 7 alpha-hydroxylase. The
      enterohepatic flux of 7 alpha-hydroxylated bile acids and the formation of
      hepatic cholesterol apparently control cholesterol 7 alpha-hydroxylase by
      different mechanisms.

PMID- 1993649
TI  - 13C NMR evidence that substitution of glutamine for arginine 3500 in familial
      defective apolipoprotein B-100 disrupts the conformation of the receptor-binding
      domain.
AB  - Familial defective apoB-100 is a genetic mutation that is characterized by
      abnormal low density lipoprotein (LDL) and moderate hypercholesterolemia.
      Heterozygotes for this disorder possess two populations of LDL. One has normal
      receptor binding, and the other, which can be isolated by monoclonal antibody 19
      immunoaffinity chromatography, has almost no binding activity. The mutation that
      disrupts binding is a Gln for Arg substitution of apoB-100 residue 3500. NMR
      spectra of LDL containing (13CH3)2Lys residues show that chemically modified Lys
      exist in two microenvironments. In normal human LDL, there are about 50 Lys with
      pK 8.9 and 170 Lys with pK 10.5; an upper limit of 10 pK 8.9 Lys may be
      particularly involved in binding to the LDL receptor. Examination of the mixture
      of normal LDL and mutant LDL from five patients shows that the latter have fewer
      pK 8.9 Lys. In purified defective LDL at least seven Lys are redistributed from
      the active to normal pool. The CD spectra of mutant and normal LDL are identical.
      Therefore, substitution of Gln for Arg at position 3500 induces a change in local
      conformation which disrupts the receptor-binding domain of apoB-100.

PMID- 1993650
TI  - Developmental changes in the expression of high mobility group chromosomal
      proteins.
AB  - The high mobility group (HMG) chromosomal proteins may modulate the structure of
      distinct regions in chromatin, thereby affecting processes such as development
      and differentiation. Here we report that the levels of the HMG chromosomal
      proteins and their mRNAs change significantly during erythropoiesis. Erythroid
      cells from 5-day chicken embryos contain 2.5-10 times more HMG mRNAs than cells
      from 14-day embryos, whereas circulating cells from adult animals are devoid of
      HMG and most other mRNAs. Nuclear run-off experiments and Northern analysis of
      RNA from various developmental stages and from Percoll-fractionated cells
      indicate that the genes are transcribed in early cells of either the primitive or
      definitive erythroid lineage. The rate of synthesis of the various HMGs changes
      during erythropoiesis; in erythroid cells from 7-day embryos the ratio of HMG-14b
      or HMG-17 to HMG-14a is, respectively, 8 and 10 times lower than in 9-day
      erythroids. HMG-14a, the major chicken HMG-14 species, is synthesized mainly in
      primitive cells, while HMG-14b is preferentially synthesized in definitive cells.
      Thus, the change from primitive to definitive erythroid lineage during
      embryogenesis is accompanied by a change in the expression of HMG chromosomal
      proteins. Conceivably, these changes may affect the structure of certain regions
      in chromatin; however, it is not presently clear whether the switch in HMG
      protein gene expression is a consequence or a prerequisite for proper
      differentiation.

PMID- 1993651
TI  - Primary structure of bovine conglutinin, a member of the C-type animal lectin
      family.
AB  - We report the complete amino acid sequence of bovine conglutinin obtained by
      structural characterization of peptides derived from the protein by various
      chemical and enzymatic fragmentation methods. The protein consists of 351 amino
      acid residues including 55 apparent Gly-X-Y repeats with two interruptions. This
      171-residue-long collagenous domain separates a short noncollagenous NH2-terminal
      region of 25 residues from the 155-residue-long globular COOH terminus revealing
      the structural relation of conglutinin with mannose-binding proteins, pulmonary
      surfactant-associated proteins, and a complement component C1q. Eight
      hydroxylysine residues were found in the collagenous domain. All of these
      hydroxylysine residues which occupy a Y position in a Gly-X-Y triplet are
      possible glycosylation sites since no phenylthiohydantoin amino acid was
      identified in automated Edman degradation cycles corresponding to these sites.
      The noncollagenous COOH domain of conglutinin, on the other hand, contains a
      carbohydrate recognition domain which shares substantial sequence homology with C
      type animal lectins. Conglutinin has the greatest sequence similarity with
      mannose-binding proteins and pulmonary surfactant-associated proteins.

PMID- 1993652
TI  - Ascorbate- and dehydroascorbic acid-mediated reduction of free radicals in the
      human erythrocyte.
AB  - Nitroxides were used as models of persistent free radicals to study the
      antioxidant function of ascorbic acid in the human erythrocyte. It was concluded
      that: 1) ascorbate and other reductant(s) derived from dehydroascorbic acid (DHA)
      in the presence of thiols are the only significant reducing agents for
      nitroxides, 2) glutathione and DHA reduce nitroxides by a process that cannot be
      inhibited by ascorbic acid oxidase, 3) erythrocytes can be depleted of ascorbic
      acid by exhaustive washing in the presence of membrane-permeable cationic
      nitroxides such as N,N-dimethylamino-Tempo, 4) ascorbate-depleted cells do not
      reduce nitroxides; however, nitroxide reduction is restored when the cells are
      incubated with DHA, 5) reduction of nitroxides in ascorbate-depleted, DHA-treated
      cells is significantly faster than in buffered solutions of DHA and glutathione,
      6) several equivalents of nitroxide are reduced relative to the intracellular
      ascorbate pool, 7) sustained nitroxide reduction is observed even when most of
      the intracellular ascorbate is oxidized, 8) spin trapping of oxyradicals in tert
      butyl hydroperoxide-treated cells is accelerated with ascorbate depletion and
      inhibited with ascorbate loading, 9) ascorbate can be quantified within intact
      cells by analyzing the initial reduction rates of membrane-permeable cationic
      nitroxides, and 10) DHA-stimulated reduction of cationic nitroxides is slower and
      less extensive in erythrocytes deficient in glucose-6-phosphate dehydrogenase
      than in normal erythrocytes.

PMID- 1993653
TI  - Kinetic mechanism of NAD:malic enzyme from Ascaris suum in the direction of
      reductive carboxylation.
AB  - Initial velocity studies in the absence and presence of product and dead-end
      inhibitors suggest a steady-state random mechanism for malic enzyme in the
      direction of reductive carboxylation of pyruvate. For this quadreactant enzymatic
      reaction (Mn2+ is a pseudoreactant), initial velocity patterns were obtained
      under conditions in which two substrates were maintained at saturating
      concentrations while one reactant was varied at several fixed concentrations of
      the other. Data from the resulting reciprocal plots, analyzed in terms of a
      bireactant mechanism, are consistent with a sequential mechanism with an
      obligatory order of addition of metal prior to pyruvate. NAD is competitive
      against NADH whether pyruvate and CO2 are maintained at low or high
      concentrations, whereas it is noncompetitive against pyruvate and CO2. Thio-NADH,
      alpha-ketobutyrate, and nitrite were used as dead-end analogs of NADH, pyruvate,
      and CO2, respectively. Thio-NADH is competitive against NADH, whereas it is
      noncompetitive against pyruvate and CO2, in accordance with a random mechanism.
      alpha-Ketobutyrate and nitrite gave noncompetitive inhibition against all
      substrates. The noncompetitive patterns observed for alpha-ketobutyrate versus
      pyruvate and nitrite versus CO2 suggest binding of the inhibitor to both the
      E.Mn.NADH and E.Mn.NAD complexes. Primary deuterium isotope effects are equal on
      all kinetic parameters, in agreement with the random mechanism, and suggest equal
      off-rates for NAD from E.Mn.NAD as well as pyruvate and NADH from
      E.Mn.NADH.pyruvate. Data are consistent with an overall symmetry in the malic
      enzyme reaction in the two reaction directions with a requirement for metal bound
      prior to pyruvate and malate.

PMID- 1993654
TI  - Reconstitution of the high affinity epidermal growth factor receptor on cell-free
      membranes after transmodulation by platelet-derived growth factor.
AB  - We have prepared plasma membranes from Balb/c 3T3 fibroblasts to study the
      transmodulation of the high affinity epidermal growth factor (EGF) receptor.
      Although phorbol esters do not transmodulate the high affinity EGF receptors on
      these membranes, the addition of platelet-derived growth factor (PDGF) or EGF to
      the membranes leads to the loss of high affinity EGF binding and to the
      phosphorylation of several membrane proteins, including the EGF receptor. The EGF
      receptor is phosphorylated at tyrosine residues although we have not yet
      established if this represents direct phosphorylation by the PDGF receptor kinase
      or is mediated by activation of other cell membrane-associated tyrosine kinases.
      Upon treatment of the membranes with PDGF, four major phosphoproteins (of
      apparent molecular masses of 69, 56, 38, and 28 kDa) are released from the
      membrane and can be retrieved from the supernatant fluid using a reversed-phase
      cartridge. As assessed by immunoprecipitation with an anti-phosphotyrosine
      antibody, all four proteins appear to be phosphorylated on tyrosine. The time
      course of dissociation of these proteins from the membranes closely parallels the
      loss of high affinity EGF receptors. The high affinity EGF receptor can be
      reconstituted on PDGF-transmodulated membranes by treating the supernatant fluid
      with alkaline phosphatase and adding the mixture to the membranes. It appears
      that dephosphorylation of the released proteins is sufficient to allow
      reassociation with the membranes and formation of the high affinity EGF receptor
      complex.

PMID- 1993655
TI  - Relative efficiencies of the bacterial, yeast, and human DNA methyltransferases
      for the repair of O6-methylguanine and O4-methylthymine. Suggestive evidence for
      O4-methylthymine repair by eukaryotic methyltransferases.
AB  - The suicidal inactivation mechanism of DNA repair methyltransferases (MTases) was
      exploited to measure the relative efficiencies with which the Escherichia coli,
      human, and Saccharomyces cerevisiae DNA MTases repair O6-methylguanine (O6MeG)
      and O4-methylthymine (O4MeT), two of the DNA lesions produced by mutagenic and
      carcinogenic alkylating agents. Using chemically synthesized double-stranded 25
      base pair oligodeoxynucleotides containing a single O6MeG or a single O4MeT, the
      concentration of O6MeG or O4MeT substrate that produced 50% inactivation (IC50)
      was determined for each of four MTases. The E. coli ogt gene product had a
      relatively high affinity for the O6MeG substrate (IC50 8.1 nM) but had an even
      higher affinity for the O4MeT substrate (IC50 3 nM). By contrast, the E. coli Ada
      MTase displayed a striking preference for O6MeG (IC50 1.25 nM) as compared to
      O4MeT (IC50 27.5 nM). Both the human and the yeast DNA MTases were efficiently
      inactivated upon incubation with the O6MeG-containing oligomer (IC50 values of
      1.5 and 1.3 nM, respectively). Surprisingly, the human and yeast MTases were also
      inactivated by the O4MeT-containing oligomer albeit at IC50 values of 29.5 and 44
      nM, respectively. This result suggests that O4MeT lesions can be recognized in
      this substrate by eukaryotic DNA MTases but the exact biochemical mechanism of
      methyltransferase inactivation remains to be determined.

PMID- 1993656
TI  - Molecular identification of ADP-ribosylation factor mRNAs and their expression in
      mammalian cells.
AB  - ADP-ribosylation factors (ARFs) are approximately 20-kDa guanine nucleotide
      binding proteins that serve as GTP-dependent allosteric activators of cholera
      toxin ADP-ribosyltransferase activity. Four species of mammalian ARF, termed ARF
      1-4, have been identified by cloning. Hybridization of a bovine ARF 2 cDNA under
      low stringency with mammalian poly(A)+ RNA resulted in multiple bands that were
      subsequently assigned to the known ARF genes using ARF-specific oligonucleotide
      probes. The relative signal intensities of some bands (e.g. the 3.8- and 1.3
      kilobase (kb) mRNAs) that hybridized with the cDNA were not, however, consistent
      with the intensities observed with the individual ARF-specific oligonucleotide
      probes. These inconsistencies suggested that other ARF-like mRNAs were
      comigrating with known ARF mRNAs. To explore this possibility, a cyclic AMP
      differentiated HL-60 Lambda ZAP library was screened using the bovine ARF 2 cDNA.
      Clones corresponding to known ARF genes (1, 3, and 4) were identified by
      hybridization of positive clones with oligonucleotide probes specific for each
      ARF species; ARF 2 cDNA-positive, oligonucleotide-negative clones were sequenced.
      Two new ARF-like genes, ARF 5 and 6, encoding proteins of 180 and 175 amino
      acids, respectively, were identified. Both proteins contain consensus sequences
      believed to be involved in guanine nucleotide binding and GTP hydrolysis. ARF 5
      was most similar in deduced amino acid sequence to ARF 4, which also has 180
      amino acids. ARF 6, whose deduced amino acid sequence is identical with that of a
      putative chicken pseudogene (CPS1) except for a serine/threonine substitution,
      was different from other ARF species in size and deduced amino acid sequence.
      With mammalian poly(A)+ RNA from a variety of tissues and cultured cells, ARF 5
      preferentially hybridized with a 1.3-kb mRNA, whereas ARF 6 hybridized with 1.8-
      and 4.2-kb mRNAs. The fact that the sizes of these mRNAs are similar to those of
      other ARFs (ARF 1, 1.9 kb; ARF 2, 2.6 kb; ARF 3, approximately 3.8 and 1.3 kb;
      ARF 4, 1.8 kb) explain the previously observed inconsistencies between the cDNA
      and ARF-specific oligonucleotide hybridization patterns. All six ARF cDNAs are
      more similar to each other than to other approximately 20-kDa guanine nucleotide
      binding proteins.

PMID- 1993657
TI  - Agonist-induced endocytosis and signal generation in adrenal glomerulosa cells. A
      potential mechanism for receptor-operated calcium entry.
AB  - The relationships between receptor-mediated endocytosis and the generation of
      intracellular signals were analyzed in angiotensin II (AII)-stimulated adrenal
      glomerulosa cells. In cells equilibrated with 125I-AII analogs at 4 degrees C,
      specifically bound agonist but not antagonist AII derivatives were rapidly
      internalized at 37 degrees C. AII-induced internalization was not influenced by
      the presence or absence of extracellular Ca2+ but was inhibited by treatment with
      phenylarsine oxide (PAO) or by arresting coated pit formation with hypotonic
      shock and potassium depletion. Inhibition of internalization by PAO was prevented
      by the bifunctional sulfhydryl reagent dithiothreitol but only partially reversed
      by mercaptoethanol, and readdition of K+ restored internalization in K(+)
      depleted cells. Treatment with PAO did not impair the initial AII-induced
      elevations of inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) and cytoplasmic calcium
      [( Ca2+]i) but reduced the sustained phase of the Ins(1,4,5)P3 response by 85%
      and abolished the second phase of the cytoplasmic Ca2+ response; these responses
      were restored by concomitant treatment with dithiothreitol. Inhibition of AII
      receptor internalization by K+ depletion also caused selective loss of the
      sustained phase of the AII-induced Ca2+ response. Thus, blockade of AII-receptor
      internalization has similar effects as extracellular Ca2+ deficiency, which
      abolishes the sustained but not the early AII-induced increases in Ins(1,4,5)P3
      production and [Ca2+]i. The close correlations between AII-induced
      internalization and the generation of Ins(1,4,5)P3 and [Ca2+]i responses suggest
      that endocytosis of the agonist-receptor complex is necessary to maintain the
      production of these intracellular signals. It is also possible that receptor
      operated vesicular uptake of extracellular Ca2+ makes a significant contribution
      to the sustained [Ca2+]i responses of certain agonist-stimulated target cells.

PMID- 1993658
TI  - Heat shock impairs the interaction of cap-binding protein complex with 5' mRNA
      cap.
AB  - Cell-free protein synthesizing systems prepared from heat-shocked Ehrlich cells
      retain the inhibition of translation that is seen at the cellular level.
      Recently, we showed that a highly purified cap-binding protein complex composed
      of the p220 and p28 subunits of eukaryotic initiation factor 4F, in a 1:1 molar
      ratio, restores protein synthesis in these cell-free translation systems
      (Lamphear, B.J., and Panniers, R. (1990) J. Biol. Chem. 265, 5333-5336). Here we
      have estimated the amount of cap-binding complex in cell extracts that can
      restore protein synthesis in heat-shocked cells. We find reduced restoring
      activity in heat-shocked cell extracts. Further, less cap-binding complex can be
      purified by 7-methyl-guanosine triphosphate Sepharose affinity chromatography
      from heat-shocked cell extracts, and we conclude that heat shock impairs the
      binding of complex to 5' mRNA cap. We have ruled out proteolysis and competitive
      inhibitors as mediators of this impairment. However we cannot distinguish between
      two possible explanations: (i) reduced association of p220 with p28 or (ii) a non
      competitive inhibitor blocks complex binding to cap. We have also examined the
      affect of heat shock on the phosphorylation state of two forms of p28, p220.p28
      complex and p28 free of p220. Both forms have reduced levels of phosphorylation
      during heat shock. The significance of these changes is discussed.

PMID- 1993659
TI  - Specific degenerate codons enhanced selective expression of human parathyroid
      hormone in Escherichia coli.
AB  - Specific degenerate codons in the amino-terminal region of a synthetic human
      parathyroid hormone (PTH) gene exerted dramatic effects on both products and
      yield of expression of this 84-amino acid polypeptide in Escherichia coli. With
      adenine-rich degenerate codons constituting the PTH-(1-5) region, intact PTH has
      been expressed as the only PTH product at 6.5 mg/liter. In contrast, with guanine
      rich degenerate codons, the predominent product was analogue PTH-(8-84). Use of
      cytosine- or thymine-rich degenerate codons generated only a small amount of
      immunoreactive product (0.2 mg/l). With the amino terminal region reconstituted
      with adenine-rich degenerate codons, the mid and carboxyl regions of the
      synthetic gene were also reconstructed to imitate the E. coli-favored codon
      degeneracy. Expression yielded the intact PTH at 20 mg/liter. Gel electrophoresis
      and Western blots, with antibodies specific to the amino or carboxyl terminus of
      PTH, indicated only a single PTH-related polypeptide, with the same mobility as a
      synthetic intact PTH sample. Amino acid sequencing, composition analysis, mass
      spectrometry, and the adenylate cyclase bioassays confirmed the purified product
      as the processed intact PTH.

PMID- 1993660
TI  - The primary structure of the Fab fragment of protein KAU, a monoclonal
      immunoglobulin M cold agglutinin.
AB  - The complete amino acid sequence of the Fab fragment of protein KAU, a human
      monoclonal cold agglutinin (IgMk) with anti-I activity, was determined. The light
      chain (L-chain) consists of 215 residues; the variable (V)L region belongs to the
      Hum/Kv325/kIIIb sub-subgroup that is preferentially selected in human IgM
      autoimmune response. The joining (J) region is encoded by the Jk4 gene, and the
      constant region (C)L domain expresses the km3 allotypic marker. The Fd fragment
      contains 232 amino acids, and 120 of them comprise the variable domain. The VH
      region corresponds to the VHIV subgroup and is closely related to the VHIV 2.1
      gene isolated from genomic DNA expressed in peripheral blood of a healthy
      Caucasian. The complementary-determining region 1 has a unique amino acid (Asp)
      at position 31, and the complementary-determining region 3 codified by the
      diversity segment (D) gene, shows poor homology with other known D sequences. The
      joining segment with two unusual substitutions at the D-J junction is encoded by
      the JH4 gene. Thus, cold agglutinin KAU is an IgM, VkIIIb-Jk4-km3; VHIV-JH4-C mu.

PMID- 1993661
TI  - Purification and characterization of Tet(M), a protein that renders ribosomes
      resistant to tetracycline.
AB  - The tet(M) tetracycline resistance gene has been found in a wide variety of
      clinically important bacteria. It has been shown previously (Burdett, V. (1986)
      J. Bacteriol. 165, 564-569) that the tet(M) gene product mediates resistance at
      the level of protein synthesis as judged by in vitro assay. Using this assay,
      large amounts of protein were purified from an Escherichia coli overproducer
      expressing the gene under control of a T7 promoter. The purified activity
      consists of a single polypeptide of molecular weight 68,000 by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis, and was confirmed to be the tet(M)
      gene product by amino-terminal sequence analysis. Purified Tet(M) has an
      associated ribosome-dependent GTPase with the specific activity being similar to
      that of the corresponding activity associated with elongation factor G. Since
      Tet(M) also displays substantial homology to elongation factor G throughout its
      length, Tet(M) may function as an analog of this elongation factor.

PMID- 1993663
TI  - Kinetics of dissociation of the tubulin-colchicine complex. Complete reaction
      scheme and comparison to thermodynamic measurements.
AB  - The slow dissociation reaction of the tubulin-colchicine complex has been
      characterized in purified calf brain tubulin and microtubule protein
      preparations, using [3H]colchicine and fluorometric measurements. It fits to a
      single exponential phase, within the accuracy of these measurements. The
      dissociation is a kinetically unfavorable reaction, with activation energy values
      of 114 +/- 10 and 94 +/- 10 kJ mol-1 (purified tubulin and microtubule protein,
      respectively). The kinetic scheme previously proposed for the tubulin-colchicine
      association (Lambeir, A., and Engelborghs, Y. (1981) J. Biol. Chem. 256, 3279
      3282) is: T + C K1 in equilibrium TC k2 in equilibrium k-2 (TC)' where step 1 is
      a fast reversible binding and step 2 is a slow conformational change, whose
      backward rate constant (k-2) was neglected for the association study. This
      kinetic scheme has now been completed to include the measurements of the rate
      limiting dissociation step (k-2), and of the purified calf brain tubulin
      preparation. The overall binding standard free energy change, calculated from the
      kinetic measurements, is -42.0 +/- 0.1 kJ mol-1 (fast phase of binding in 10 mM
      sodium phosphate buffer, 0.1 mM GTP, pH 7.0, at 37 degrees C). The binding is
      exothermic and the calculated enthalpy change is -26 +/- 13 kJ mol-1, which
      coincides with the recently determined calorimetric enthalpy value, -21 +/- 2 kJ
      mol-1 (Menendez, M., Laynez, J., Medrano, F. J., and Andreu, J. M. (1989) J.
      Biol. Chem. 264, 16367-16371), suggesting that the kinetic scheme and
      measurements are essentially correct.

PMID- 1993662
TI  - Isolation and sequencing of cDNA clones encoding the Dictyostelium discoideum
      30,000-dalton actin-bundling protein.
AB  - The Dictyostelium 30,000-dalton protein is a calcium-regulated actin filament
      bundling protein which has been suggested to contribute to the structure and
      reorganization of filopodia and pseudopodia accompanying cell movements. cDNAs
      encoding this protein were isolated using antibody and oligonucleotide probes to
      screen cDNA libraries in phage lambda. The sequence of the cDNA predicts a
      protein of 295 amino acids with a molecular weight of 33,355. The sequence
      reveals two EF-hand calcium-binding regions that provide a structural explanation
      for calcium regulation of the activity of this protein. The putative calcium
      binding region of the 30,000-dalton protein has similarity to sequences of other
      calcium-regulated actin-binding proteins such as alpha-actin and fimbrin. One
      region of the sequence with similarity to both Dictyostelium gelation factor (ABP
      120) and fructose bisphosphate aldolase is a potential actin-binding sequence. A
      highly charged region of the protein is similar to a sequence in human cytovillin
      that is repeated eight times in chicken gizzard caldesmon. No strong homology to
      previously identified actin-binding sequences of other actin-binding proteins is
      apparent. Results from Southern blot experiments indicate that the 30,000-dalton
      protein is encoded by a single gene in the Dictyostelium genome.

PMID- 1993664
TI  - Hydroxylation of 4-methylphenylalanine by rat liver phenylalanine hydroxylase.
AB  - Rat liver phenylalanine hydroxylase that has been activated with lysolecithin
      catalyzes the hydroxylation of 4-methylphenylalanine in the presence of a pterin
      cofactor. Two products, 4-hydroxymethylphenylalanine and 3-methyltyrosine, can be
      detected. The total amount of amino acids hydroxylated is equal to the amount of
      tetrahydropterin oxidized. Isotopic labeling studies with 18O2 and H2(18)O show
      that the hydroxyl groups of both products are derived from molecular oxygen and
      not from water. Results obtained with 2H-labeled substrates support the
      conclusion that these products are formed via different mechanistic pathways. Our
      previous investigations on substrate analogs, as well as the present results,
      indicate that a highly reactive oxygen-containing intermediate, such as an enzyme
      bound iron-oxo compound, must be the hydroxylating species. Our present results
      could stimulate further discussion of the possibility that the reaction mechanism
      for the "NIH-shift" of the methyl group may not involve the spontaneous opening
      of an epoxide intermediate.

PMID- 1993665
TI  - Identification and characterization of RNA polymerase sigma factor from
      Micrococcus luteus.
AB  - The promoters of Micrococcus luteus, a bacterium whose chromosomal DNA has a high
      G + C content (74%), diverge from the consensus prokaryotic promoter in having GC
      rich DNA sequences at less important positions (Nakayama, M., Fujita, N., Ohama,
      T., Osawa, S., and Ishihama, A. (1989) Mol. Gen. Genet. 218, 384-389). In order
      to compare the promoter selectivity of RNA polymerase between M. luteus and
      Escherichia coli, we purified the enzyme from both organisms. The sets of
      promoters recognized by the two RNA polymerases were found to overlap partly.
      Some, but not all, E. coli promoters were found to be correctly transcribed in
      vitro by M. luteus RNA polymerase as well as the E. coli enzyme. One molecular
      species of M. luteus sigma factor, with the apparent molecular mass of 60 kDa,
      was isolated from purified RNA polymerase. By the addition of either M. luteus or
      E. coli core enzyme it was reconstituted into active holoenzyme. Likewise, M.
      luteus core enzyme was reconstituted into a hybrid holoenzyme by the addition of
      E. coli sigma subunit. Both hybrid holoenzymes were, however, able to initiate
      transcription only from promoters which were recognized by both of the native
      holoenzymes.

PMID- 1993666
TI  - Metabolic conversion of dicarboxylic acids to succinate in rat liver homogenates.
      A stable isotope tracer study.
AB  - The metabolic conversion of dicarboxylic acids into succinate and other
      gluconeogenic intermediates in rat liver homogenates was investigated using
      [1,2,4-13C4]dodecanedioic acid as tracer. Isotope enrichments in 3
      hydroxybutyrate, succinate, fumarate, and malate, as well as dicarboxylates
      (dodecanedioic, sebacic, suberic, and adipic acids) were measured with selected
      ion monitoring capillary column gas chromatograph-mass spectrometry. Significant
      enrichment in the M + 4 (four labeled carbons) ion of succinate (0.4-2.9%) was
      detected, unequivocally demonstrating the direct conversion of dicarboxylate into
      succinate. In addition, significant enrichment of the M + 2 ion of succinate was
      also observed. This labeled species was generated from labeled acetyl-CoA through
      the tricarboxylic acid cycle. The partition of acetyl-CoA into the tricarboxylic
      acid cycle relative to ketone body formation was higher in the beta oxidation of
      dicarboxylate than monocarboxylate. Therefore, in addition to the production of
      succinate, the beta oxidation of dodecanedioate resulted in the channeling of the
      acetyl-CoA produced to the tricarboxylic acid cycle instead of to acetoacetate
      production. The enrichments in lower chain dicarboxylates are consistent with a
      partial bidirectional beta oxidation of dodecanedioic acid. In addition to the
      expected M + 0 and M + 4 labels, significant M + 2 species were detected in
      suberic and adipic acids. These M + 2-labeled species were produced from the
      released free dicarboxylate intermediates which were then reactivated and
      metabolized. In these experiments, the overall succinate production was derived
      4% from the direct conversion of dodecanedioic acid and 11% from the indirect
      route via acetyl-CoA through tricarboxylic acid.

PMID- 1993667
TI  - Identification of a highly conserved domain in the EcoRII methyltransferase which
      can be photolabeled with S-adenosyl-L-[methyl-3H]methionine. Evidence for UV
      induced transmethylation of cysteine 186.
AB  - DNA methyltransferases can be photolabeled with S-adenosyl-L-methionine (AdoMet).
      Specific incorporation of radioactivity has been demonstrated after photolabeling
      with either [methyl-3H]AdoMet or [35S]AdoMet (Som, S., and Friedman, S. (1990) J.
      Biol. Chem. 265, 4278-4283). The labeling is believed to occur at the AdoMet
      binding site. With the purpose of localizing the site responsible for [methyl
      3H]AdoMet photolabeling, we cleaved the labeled EcoRII methyltransferase by
      chemical and enzymatic reactions and isolated the radiolabeled peptides by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis and high pressure liquid
      chromatography. The labeled peptides were identified by amino-terminal
      sequencing. A common region was localized which accounted for 65-70% of the total
      label. This region includes a highly conserved core sequence present in all DNA
      (cytosine 5)-methyltransferases. One such fragment was digested further with
      chymotrypsin, and amino acid analysis of the resulting 3H-labeled peptide was
      consistent with the sequence Ala-Gly-Phe-Pro-(Cys)-Gln-Pro-Phe-Ser-Leu. However,
      the cysteine residue was not recovered as carboxymethylcysteine. The Pro-Cys bond
      was found to be protected from cleavage at cysteine residues after cyanylation.
      These results suggest that the cysteine residue is modified by the labeling
      reaction. The chymotryptic fragment was hydrolyzed enzymatically to single amino
      acids, and the labeled amino acid was identified as S-methylcysteine by thin
      layer chromatography. These results indicate that the cysteine residue is located
      at or close to the AdoMet binding site of EcoRII methyltransferase.

PMID- 1993668
TI  - Interleukin-6 responsiveness and cell-specific expression of the rat kininogen
      gene.
AB  - The serum concentration of rat T1 kininogen increases 20-30-fold in response to
      acute inflammation, an induced hepatic synthesis regulated primarily at the
      transcriptional level. To analyze the cis-regulatory elements responsible for the
      induced transcription, we fused a 1.6-kilobase segment of the rat T1 kininogen
      promoter to a reporter gene, chloramphenicol acetyltransferase (CAT). The
      resultant chimeric DNA was transfected into cultured cells. In transient
      transfection assays, this 5'-flanking sequence was sufficient to confer cell
      specific expression: CAT activity was readily detectable when the construct was
      transfected into liver-derived cells, but it was not detectable in nonliver
      cells. Furthermore, when liver cells (Hep3B) transfected with this construct were
      treated with conditioned medium prepared from activated mixed lymphocyte cultures
      or with recombinant interleukin-6 (IL-6), a 5-fold increase in CAT activity was
      detected. Addition of dexamethasone to the conditioned medium or to IL-6 showed
      synergistic effects and resulted in a 10-fold increase in CAT activity. In
      contrast, when IL-1 was used with IL-6, induction of CAT activity was inhibited.
      Deletion analyses revealed two regions important for tissue-specific and induced
      regulation of T1 kininogen: sequences proximal to base pair -73 conferred
      enhanced expression in liver-derived cells and a distal region that conferred
      responsiveness to conditioned medium, recombinant IL-6, and dexamethasone. This
      responsive element had properties of an inducible transcriptional enhancer, and
      it was functional in both liver and nonliver cells when placed immediately
      upstream of a thymidine kinase promoter.

PMID- 1993669
TI  - Calcium binding to thermitase. Crystallographic studies of thermitase at 0, 5,
      and 100 mM calcium.
AB  - The three-dimensional crystal structure of thermitase complexed with eglin-c in
      the presence of 100 mM calcium has been determined and refined at 2.0-A
      resolution to a R-factor of 16.8%. This crystal structure is compared with
      previously determined structures of thermitase at 0 and 5 mM calcium
      concentration. In the presence of 100 mM calcium all three calcium binding sites
      in thermitase are fully occupied. At 100 mM CaCl2 the "weak" calcium binding is
      occupied by a calcium ion, which is chelated by three protein ligands and four
      water molecules in a pentagonal bipyramid geometry. Thermitase has, apparently, a
      monovalent and divalent cation binding position at 2.5-A distance from each other
      at this site. At low calcium concentrations the monovalent-ion position is
      occupied by a sodium or potassium ion. The "medium strength" binding site shows
      in the presence of 100 mM CaCl2 a square antiprism arrangement with eight
      ligands, of which seven are donated by the protein. At low calcium concentrations
      we observe a distorted pentagonal bipyramid coordination at this site. The
      largest difference between these two conformations is observed for ligand Asp-60,
      which has two conformations with 0.8-A difference in C alpha positions. The
      "strong" calcium binding site has a pentagonal bipyramid coordination and is
      fully occupied in all three structures. Structural changes on binding calcium to
      the weak and "medium strength" calcium binding sites of thermitase are limited to
      the direct surroundings of these sites. Thermitase resembles in this respect
      subtilisin BPN' and does not exhibit long-range shifts as have been reported for
      proteinase K.

PMID- 1993670
TI  - The energy state of tumor-bearing rats.
AB  - Rats bearing the Walker-256 carcinosarcoma have a profoundly altered liver
      metabolite content with significant increases in the concentrations of glucose 6
      phosphate, fructose 1,6-bisphosphate, citrate, lactate, and alanine, while the
      concentrations of glucose, pyruvate, dihydroxyacetone phosphate, and glutamine
      are decreased. As a result of these changes both the cytosolic NAD+/NADH ratio
      and the cytosolic phosphorylation potential are significantly lowered while no
      changes are detected in either the cytosolic NADP+/NADPH ratio or the
      mitochondrial NAD+/NADH ratio. These hepatic changes are accompanied by marked
      increases in the circulating concentrations of lactate, non-esterified fatty
      acids, and triacylglycerols. The activities of both liver hexokinase and
      phosphofructokinase are also significantly elevated in the tumor-bearing rats.
      The changes observed both in the redox state and phosphorylation potential are in
      agreement with the energy imbalance associated with tumor burden.

PMID- 1993671
TI  - Propeptide-mediated regulation of procollagen synthesis in IMR-90 human lung
      fibroblast cell cultures. Evidence for transcriptional control.
AB  - We have demonstrated previously that the carboxyl- and amino-terminal propeptides
      of type I procollagen can inhibit procollagen synthesis by specifically
      decreasing procollagen mRNA levels. The objective of the present experiments was
      to determine the mechanism by which propeptides cause these pretranslational
      effects. IMR-90 fibroblasts were exposed to medium containing carboxyl-terminal
      propeptide of type I procollagen, and nuclear run-off assays were performed by
      hybridization to a specific alpha 1 chain type I procollagen cDNA probe. Specific
      type I procollagen transcription rates were found to be decreased by 50% in the
      presence of 75 nM carboxyl-terminal propeptide compared with control (untreated)
      cells. Total cellular transcription rates as well as beta-actin mRNA rates were
      not affected significantly by any concentration of carboxyl-terminal propeptide.
      Propeptide radiolabeled with 125I was found to be taken up by cultured cells.
      Furthermore, exogenous carboxyl-terminal propeptide levels increased in the
      cytosolic compartment and eventually reached a steady-state level of 18 +/- 2
      pmol/g cell protein by 30 min. Of particular interest was the finding that levels
      of radiolabeled carboxyl-terminal propeptide were also detected in the nuclear
      fraction and increased with time, reaching a plateau after 60 min of incubation.
      Incubation of nuclei from IMR-90 cells in medium containing varying
      concentrations of carboxyl-terminal propeptide resulted in nuclear transcription
      rates that were decreased by 40% compared with untreated controls. beta-Actin
      nuclear message levels remained unchanged under identical conditions. We conclude
      that carboxyl-terminal propeptide of type I procollagen can be internalized and
      become associated with the nuclear compartment. This suggests a feedback
      regulatory role on procollagen synthesis by a direct effect on procollagen gene
      transcription.

PMID- 1993672
TI  - Plasma membrane fractions from rat liver contain a phosphatidate phosphohydrolase
      distinct from that in the endoplasmic reticulum and cytosol.
AB  - Assays for two distinct phosphatidate phosphohydrolase activities were
      established based upon a differential inhibition by N-ethylmaleimide (NEM). The
      activity that is insensitive to this reagent in rat liver is predominantly in the
      plasma membrane fraction, whereas the NEM-sensitive activity is in the cytosolic
      and microsomal fractions. The NEM-insensitive activity is further distinguished
      from the NEM-sensitive phosphohydrolase by: (a) being relatively stable to heat;
      (b) not being inhibited by phenylglyoxal, butane-2,3-dione, cyclohexane-1,2
      dione, 2,4-dinitrofluorobenzene, 7-chloro-4-nitrobenz-2-oxa-1,3-diazole, and
      diethyl pyrocarbonate; (c) being inhibited by NaF and phosphatidylcholine; and
      (d) not being stimulated by Mg2+. The NEM-insensitive activity was specific for
      phosphatidate. Both phosphohydrolase activities could be inhibited by
      chlorpromazine, propranolol, sphingosine, and spermine. The NEM-sensitive
      phosphatidate phosphohydrolase activity was increased by incubating hepatocytes
      for 12 h with glucagon and dexamethasone, and this effect was antagonized by
      insulin. The NEM-sensitive phosphohydrolase is concluded to be involved in
      glycerolipid synthesis. The activity of the NEM-insensitive phosphohydrolase was
      not altered by preincubation of rat hepatocytes in the short or long term with
      vasopressin, glucagon, insulin, triiodothyronine, or dexamethasone, but it might
      be modulated indirectly by sphingosine. The NEM-insensitive enzyme of the plasma
      membranes could be involved in signal transduction via the agonist-stimulated
      degradation of phosphatidylcholine through the phospholipase D pathway.

PMID- 1993673
TI  - Regulation of the transferrin-independent iron transport system in cultured
      cells.
AB  - Mammalian cells accumulate iron via the binding of transferrin to high affinity
      surface receptors, or through a transferrin-independent pathway which involves
      the uptake of iron-organic anion chelates by a membrane-based transport system.
      Previously we determined that the transferrin-independent transport system was
      present on a wide variety of cultured cells (Sturrock, A., Alexander, J., Lamb,
      J., Craven, C. M., and Kaplan, J. (1990) J. Biol. Chem. 265, 3139-3145). In this
      communication we demonstrate that the transferrin-independent iron uptake system
      is regulated differently than the transferrin-mediated pathway. The activity of
      the transferrin-independent system was unaffected by changes in cellular growth
      rate, induction of DNA synthesis and cell division, or depletion of cellular
      iron. Exposure of cells to ferric or ferrous iron, however, resulted in a time
      dependent increase in transport activity, due to a change in Vmax with no change
      in Km. Increased transport activity was seen in a variety of cultured cell types,
      occurred in the presence of cycloheximide, and persisted for hours after removal
      of iron. The ability of other transition metals to induce changes in transport,
      or to compete with iron for accumulation by the transferrin-independent uptake
      system, was critically dependent on the composition of the media in which the
      cells were incubated. Metals such as Cu2+ or Zn2+, but not Cd2+ or Mn2+, when
      dissolved in a balanced salt solution buffered with 4-(2-hydroxyethyl)-1
      piperazineethanesulfonic acid, induced changes in the transferrin-independent
      iron transport system. The same metals which induced changes in transport were
      ineffective in media containing amino acids, ascorbate, or N-[2-hydroxy-1,1
      bis(hydroxymethyl)ethyl]glycine. The Vmax of the transferrin-independent iron
      transport system was also elevated by increases in intracellular Ca2+. The effect
      of iron on transport activity, however, did not result from an iron-induced
      release of intracellular Ca2+. These results suggest a novel form of regulation
      in which the presence of extracellular iron induces the appearance of previously
      cryptic transporters and thus accelerates the clearance of potentially toxic
      molecules.

PMID- 1993674
TI  - Human NAD(+)-dependent mitochondrial malic enzyme. cDNA cloning, primary
      structure, and expression in Escherichia coli.
AB  - Mitochondrial NAD(+)-dependent malic enzyme (EC 1.1.1.40) is expressed in rapidly
      proliferating cells and tumor cells, where it is probably linked to the
      conversion of amino acid carbon to pyruvate. In this paper, we report the cDNA
      cloning, amino acid sequence, and expression in Escherichia coli of functional
      human NAD(+)-dependent mitochondrial malic enzyme. The cDNA is 1,923 base pairs
      long and contains an open reading frame coding for a 584-amino acid protein. The
      molecular mass is 65.4 kDa for the unprocessed precursor protein. Comparison of
      the amino acid sequence of the human protein with the published NADP(+)-dependent
      mammalian cytosolic or plant chloroplast malic enzymes reveals highly conserved
      regions interrupted with long stretches of amino acids without significant
      homology. Expression of the processed protein in E. coli yielded an enzyme with
      the same kinetic and allosteric properties as malic enzyme purified from human
      cells.

PMID- 1993675
TI  - Localization of a region of the S1 subunit of pertussis toxin required for
      efficient ADP-ribosyltransferase activity.
AB  - Purified recombinant S1 subunit of pertussis toxin (rS1) possessed similar NAD
      glycohydrolase and ADP-ribosyltransferase activities as S1 subunit purified from
      pertussis toxin. Purified rS1 and C180 peptide, a deletion peptide which contains
      amino acids 1-180 of rS1, had Km values for NAD of 24 and 13 microM and kcat
      values of 22 and 24 h-1, respectively, in the NAD glycohydrolase reaction. In
      contrast, under linear velocity conditions, the C180 peptide possessed less than
      1% of the ADP-ribosyltransferase activity of rS1 using transducin as target.
      Radiolabeled tryptic peptides of transducin that had been ADP-ribosylated by
      either rS1 or C180 peptide were identical which suggested that both rS1 and C180
      peptide ADP-ribosylated the same amino acid within transducin. To extend the
      functional primary amino acid map of the S1 subunit, two carboxyl-terminal
      deletions were constructed. One deletion, C195, removed the 40 carboxyl-terminal
      amino acids and the other, C219, removed the 16 carboxyl-terminal amino acids of
      the S1 subunit. Both C195 and C219 migrated in reduced sodium dodecyl sulfate
      polyacrylamide gel electrophoresis with apparent molecular masses of 22,000 and
      27,500 Da, respectively. Relative to the C180 peptide C195 possessed 10-20-fold
      increase and C219 possessed 100-150-fold increase in ADP-ribosyltransferase
      activities. In addition, C219 appeared to have the same ADP-ribosyltransferase
      activity as rS1. These studies indicate that (i) rS1, purified from Escherichia
      coli, possesses biochemical properties similar to S1 subunit purified from
      pertussis toxin, (ii) amino acids 1-180 of the S1 subunit contain residues
      required for NAD binding, N-glycosidic cleavage, and transfer of ADP-ribose to
      transducin, and (iii) residues between 181 and 219 of the S1 subunit are required
      for efficient ADP-ribosyltransferase activity.

PMID- 1993676
TI  - Autoactivation of calmodulin-dependent protein kinase II by autophosphorylation.
AB  - Autophosphorylation of calmodulin (CaM)-dependent protein kinase II (CaM-kinase
      II) under limiting conditions (2 microM ATP) decreased progressively with
      increasing concentrations of a substrate, Pro-Leu-Ala-Arg-Thr-Leu-Ser-Val-Ala-Gly
      Leu-Pro-Gly-Lys-Lys (syntide-2), suggesting a competition between the substrate
      and the autophosphorylation site(s) of the enzyme. The rate and extent of the
      generation of Ca2+/CaM-independent activity of the enzyme by autophosphorylation
      were also decreased by the presence of syntide-2. The syntide-2 phosphorylation
      in the presence of Ca2+/CaM under the limiting conditions reached a steady state,
      after a lag, when the Ca2+/CaM-independent activity reached a plateau. A linear
      relationship was observed between the activities in the presence and absence of
      Ca2+/CaM of the enzyme which had undergone various degrees of
      autophosphorylation, and the extrapolation of activity in the absence of Ca2+/CaM
      to zero gave 15-20% of the maximum activity. The steady-state rate of syntide-2
      phosphorylation in the presence of Ca2+/CaM by the enzyme that had not undergone
      prior autophosphorylation was decreased by high concentrations of syntide-2 which
      suppressed autophosphorylation as well as the generation of Ca2+/CaM-independent
      activity. These results suggest that although the nonautophosphorylated enzyme
      possesses a basal low level of Ca2+/CaM-dependent activity, autophosphorylation
      is required for full activation.

PMID- 1993677
TI  - Role of type III homology repeats in cell adhesive function within the cell
      binding domain of fibronectin.
AB  - Recombinant fibronectin (FN) fragments and their mutant proteins were produced to
      elucidate the role of type III homology repeats in cell adhesive activity within
      the cell-binding domain of FN. Cell adhesive activity of the 11.5-kDa fragment,
      the cell attachment site of the cell-binding domain, was less than 0.1% that of
      native FN despite the presence of the Arg-Gly-Asp-Ser sequence. The activity
      increased as type III homology repeats were added to the N terminus of the 11.5
      kDa fragment, and a 52-kDa fragment with four additional type III repeats had
      almost the same activity of native FN. Deletion of Arg-Gly-Asp from the fully
      active fragments completely abolished the cell adhesive activity. Deletion of one
      or two repeats from the 52-kDa fragment affected the extent of the cell adhesive
      activity, the degree of the effect being inversely correlated with the distance
      of the deletion from the type III repeat containing Arg-Gly-Asp-Ser.
      Rearrangement of type III repeats caused much loss of activity. These results
      suggest that the number and kinds of type III repeats and their correct alignment
      rather than the putative synergistic site decide the extent of the specific cell
      adhesive activity.

PMID- 1993678
TI  - Purification and characterization of Ku-2, an octamer-binding protein related to
      the autoantigen Ku.
AB  - The octamer motif (ATTTGCAT) is an important regulatory element in eukaryotic
      gene expression. A previously unidentified protein that recognizes this motif has
      been isolated from the human B cell line, Daudi. The protein, which we term Ku-2,
      bears a close resemblance to the DNA-binding autoantigen Ku. Like Ku, it is a
      heterodimer with subunits of 83 and 72 kDa; antisera raised against either
      subunit of Ku cross-react with Ku-2. Two peptides have been sequenced and show a
      strong similarity to regions in the corresponding subunits of Ku. The sequences
      are not identical, however, suggesting that Ku-2 may be a B cell homologue of Ku.
      Both Ku and Ku-2 bind to the termini of DNA duplexes, but Ku-2 also binds to an
      internal octamer motif. It is not known whether Ku shares the latter property or
      whether the octamer binding is a consequence of sequence differences between the
      two proteins. Ku-2 does not react with antisera against the POU domain of the
      octamer-binding protein Oct-2, indicating that the DNA binding domains of the two
      proteins are dissimilar despite the ability of both to bind to the octamer motif.
      We discuss the evidence for the existence of a family of octamer-binding proteins
      related to Ku.

PMID- 1993679
TI  - Pulmonary surfactant protein A (SP-A) specifically binds
      dipalmitoylphosphatidylcholine.
AB  - Phospholipids are the major components of pulmonary surfactant.
      Dipalmitoylphosphatidylcholine is believed to be especially essential for the
      surfactant function of reducing the surface tension at the air-liquid interface.
      Surfactant protein A (SP-A) with a reduced denatured molecular mass of 26-38 kDa,
      characterized by a collagen-like structure and N-linked glycosylation, interacts
      strongly with a mixture of surfactant-like phospholipids. In the present study
      the direct binding of SP-A to phospholipids on a thin layer chromatogram was
      visualized using 125I-SP-A as a probe, so that the phospholipid specificities of
      SP-A binding and the structural requirements of SP-A and phospholipids for the
      binding could be examined. Although 125I-SP-A bound phosphatidylcholine and
      sphingomyeline, it was especially strong in binding
      dipalmitoylphosphatidylcholine, but failed to bind phosphatidylglycerol,
      phosphatidylinositol, phosphatidylethanolamine, and phosphatidylserine. Labeled
      SP-A also exhibited strong binding to distearoylphosphatidylcholine, but weak
      binding to dimyristoyl-, 1-palmitoyl-2-linoleoyl-, and
      dilinoleoylphosphatidylcholine. Unlabeled SP-A readily competed with labeled SP-A
      for phospholipid binding. SP-A strongly bound dipalmitoylglycerol produced by
      phospholipase C treatment of dipalmitoylphosphatidylcholine, but not palmitic
      acid. This protein also failed to bind lysophosphatidylcholine produced by
      phospholipase A2 treatment of dipalmitoylphosphatidylcholine. 125I-SP-A shows
      almost no binding to dipalmitoylphosphatidylglycerol and
      dipalmitoylphosphatidylethanolamine. The addition of 10 mM EGTA into the binding
      buffer reduced much of the 125I-SP-A binding to phospholipids. Excess
      deglycosylated SP-A competed with labeled SP-A for binding to
      dipalmitoylphosphatidylcholine, but the excess collagenase-resistant fragment of
      SP-A failed. From these data we conclude that 1) SP-A specifically and strongly
      binds dipalmitoylphosphatidylcholine, 2) SP-A binds the nonpolar group of
      phospholipids, 3) the second positioned palmitate is involved in
      dipalmitoylphosphatidylcholine binding, and 4) the specificities of polar groups
      of dipalmitoylglycerophospholipids also appear to be important for SP-A binding,
      5) the phospholipid binding activity of SP-A is dependent upon calcium ions and
      the integrity of the collagenous domain of SP-A, but not on the oligosaccharide
      moiety of SP-A. SP-A may play an important role in the regulation of recycling
      and intra- and extracellular movement of dipalmitoylphosphatidylcholine.

PMID- 1993680
TI  - Specific localization of phosphointermediate filament protein in the constricted
      area of dividing cells.
AB  - We developed antibodies pG1 and pG2 which recognize glial fibrillary acidic
      protein (GFAP) in its phosphorylated state. Antibodies pG1 and pG2 were produced
      against two synthetic peptides, Arg-Arg-Arg-Val-Thr-phosphoSer-Ala-Ala-Arg-Arg
      phosphoSer (residues 3-13) and Pro-Gly-Pro-Arg-Leu-phosphoSer-Leu-Ala-Arg-Met-Pro
      (residues 29-39), respectively. The phosphorylation of these serine residues on
      the intact GFAP induces disassembly of glial filaments in vitro (Inagaki, M.,
      Gonda, Y., Nishizawa, K., Kitamura, S., Sato, C., Ando, S., Tanabe, K., Kikuchi,
      K., Tsuiki, S., and Nishi, Y. (1990) J. Biol. Chem. 265, 4722-4729).
      Immunofluorescence and immunoblotting studies demonstrate that both antibodies
      react specifically with mitotic astroglial cells, thereby supporting the notion
      that increased phosphorylation during mitosis may directly influence
      intracellular organization of the glial filaments. The specific distribution
      pattern of the phosphoGFAP in the mitotic cells reveals that site-specific
      phosphorylation events may make way for the locally controlled breakdown of glial
      filaments in the constricted area, before the final separation of daughter cells.

PMID- 1993681
TI  - Interaction of free apolipoproteins with macrophages. Formation of high density
      lipoprotein-like lipoproteins and reduction of cellular cholesterol.
AB  - Mouse peritoneal macrophages, loaded with cholesteryl ester by incubating with
      acetylated human low density lipoprotein containing [3H]cholesteryl oleate, were
      exposed to purified human apolipoproteins (apo) A-I, A-II, C-III, or E in aqueous
      solutions. Unesterified cholesterol was released into the medium in the presence
      of apoA-I, -A-II, or -E, accompanied by the decrease in intracellular cholesteryl
      ester. ApoC-III had no such effects. Apparent Km values of the cholesterol
      release were estimated as 0.11, 0.14, and 0.24 microM, and Vmax values 35, 11,
      and 14 micrograms of cholesterol/mg of cell protein/6 h, for apoA-I, -A-II, and 
      E, respectively. The products formed with apoA-I, -A-II, or -E in the media were
      analyzed by density gradient ultracentrifugation when the cells were preloaded
      with [3H]cholesteryl oleate-acetylated low density lipoproteins and [3H]choline.
      Free [3H]cholesterol, [3H]phosphatidylcholine, and [3H]sphingomyelin were
      detected coincidentally as a symmetric peak at the density of 1.1 in each case.
      In the complex of lipids and apoA-I or apoA-II, the weight ratios of
      apolipoprotein/cholesterol/phosphatidylcholine/sphingomyelin/lysophosphatidyl-
      choline were estimated as 2.2:1:0.6:0.2:0.07 and 4.0:1:0.5:0.3:0.07,
      respectively. Both of the products formed with apoA-I and -A-II migrated slower
      than plasma high density lipoprotein in electrophoresis on agarose gel. Because
      the Km values are as low as 1:340-400, 1:140-160, and 1:6-8 of plasma
      concentrations of apoA-I, -A-II, and -E, respectively, the results have
      physiological relevance for a function of the free apolipoproteins in
      interstitial fluid to form high density lipoprotein and to reduce cellular
      cholesterol.

PMID- 1993682
TI  - DNA binding specificity of mutant glucocorticoid receptor DNA-binding domains.
AB  - Mutation of a small number of amino acids in the DNA-binding domain of the
      estrogen receptor to the corresponding sequence of the glucocorticoid receptor
      switches the specificity of the receptor in transactivation assays (Mader, S.,
      Kumar, V., de Verneuil, H., and Chambon, P. (1989) Nature 338, 271-274). We have
      made the corresponding reciprocal mutations in the context of the glucocorticoid
      receptor DNA-binding domain and studied the binding of wild type and mutant
      purified proteins to palindromic glucocorticoid and estrogen response elements as
      well as to elements of intermediate sequence, using gel mobility shift assays. We
      show here that a protein with two altered amino acids binds glucocorticoid and
      estrogen response elements with a low but equal affinity, whereas a protein with
      an additional changed residue has a high affinity for estrogen response elements
      but still retains a considerable affinity for glucocorticoid response elements.
      Using binding sites of intermediate sequence we have further characterized the
      interaction with DNA. The in vitro DNA binding results are confirmed by in vivo
      transactivation assays in yeast. Finally we suggest a testable model for amino
      acid/base pair interactions involved in recognition by the glucocorticoid
      receptor DNA-binding domain of its target sequence.

PMID- 1993684
TI  - Purification and characterization of a mammalian polyadenylate polymerase
      involved in the 3' end processing of messenger RNA precursors.
AB  - A polyadenylate polymerase involved in the polyadenylation of pre-mRNA has been
      purified 6,000-fold to apparent homogeneity from extracts of calf thymus. In the
      last purification step, anion exchange chromatography separates the enzyme into
      three major peaks that are indistinguishable by other physical or functional
      criteria. On denaturing polyacrylamide gels, the two predominant forms of poly(A)
      polymerase have molecular weights of 57,000 and 60,000. In solution, the enzyme
      is a monomer. It polymerizes exclusively ATP. The reaction is distributive and
      proceeds linearly without any lag phase. The requirement for a primer can be
      satisfied by any of a number of polyribonucleotides. A significantly higher
      activity in the presence of Mn2+ as opposed to Mg2+ is due to a hundredfold
      higher affinity for the primer terminus. In the presence of mg2+ and of a
      specificity factor partially purified from HeLa cells, the enzyme specifically
      polyadenylates an RNA that ends at the natural adenovirus L3 polyadenylation
      site. This reaction depends on the AAUAAA polyadenylation signal.

PMID- 1993683
TI  - Interaction of the glucocorticoid receptor DNA-binding domain with DNA as a dimer
      is mediated by a short segment of five amino acids.
AB  - We have previously shown that protein-protein interactions mediate cooperative
      binding of the glucocorticoid receptor DNA-binding domain to a glucocorticoid
      response element (Dahlman-Wright, K., Siltala-Roos, H., Carlstedt-Duke, J., and
      Gustafsson, J.-A. (1990) J. Biol. Chem. 265, 14030-14035). The cooperativity of
      DNA binding is lost when the distance between the two half-sites constituting a
      glucocorticoid responsive element is altered or when their relative orientation
      is changed. We show here that mutations in the responsive element which interfere
      with cooperative DNA binding by the glucocorticoid receptor DNA-binding domain in
      vitro also abolish transactivation by the full length glucocorticoid receptor in
      vivo. We also identify a short segment in the proximity of one of the bound zinc
      ions that is required for cooperative binding of the glucocorticoid receptor DNA
      binding domain to a glucocorticoid response element. We suggest that this segment
      is involved in dimer formation of the native glucocorticoid receptor and that it
      is important for correct positioning of the dimeric molecule on the double helix
      of DNA.

PMID- 1993685
TI  - Oligosaccharide signaling in plants. Specificity of oligouronide-enhanced plasma
      membrane protein phosphorylation.
AB  - The in vitro phosphorylation by [gamma-32P]ATP of a 34-kDa plasma membrane
      associated protein (pp34) from tomato and potato is strongly enhanced in the
      presence of alpha-1,4-D-polygalacturonic acid (PGA) fragments (Farmer, E. E.,
      Pearce, G., and Ryan, C. A. (1989) Proc. Natl. Acad. Sci. U. S. A. 86, 1539-1542)
      that activate the expression of defensive and developmental genes in plant
      tissues. [gamma-35S]ATP, but not [gamma-35S]GTP, has now been found to strongly
      label pp34 in the presence of the PGA fragments. PGA-enhanced phosphorylation of
      pp34 is at one or more threonine residue(s) and therefore is the product of a
      serine/threonine kinase. alpha-1,4-L-Polyguluronic acid (PGU) enhances
      thiophosphorylation of pp34, but is less effective than PGA. beta-1,4-D
      Polymannuronic acid (PMA) is inactive. In vivo synthesis of proteinase inhibitors
      in tomato leaves in response to PGA, PGU, and PMA parallels enhancing activities
      in in vitro phosphorylation assays. The minimum oligogalacturonide lengths that
      enhance in vitro thiophosphorylation of pp34 are about 14-15 residues, which are
      near the minimum sizes of uronides required to elicit a variety of localized
      defensive and developmental responses in plants. The lengths of biologically
      active galacturonic acid oligomers are of the same length that form strong
      intermolecular complexes in solution with Ca2+. Uronide-Ca2+ complexes are
      proposed to be the active molecular species that initiate the signal transduction
      pathways regulating uronide-responsive genes.

PMID- 1993686
TI  - A novel mannose-specific and sugar specifically aggregatable lectin from the bark
      of the Japanese pagoda tree (Sophora japonica).
AB  - A new D-mannose/D-glucose-specific lectin (B-SJA-II) was isolated from the bark
      of the Japanese pagoda tree, Sophora japonica. B-SJA-II was separated from a well
      known D-galactose/N-acetyl-D-galactosamine-specific lectin (B-SJA-I) by affinity
      chromatography on lactamyl-Sepharose, then purified by affinity chromatography on
      maltamyl-Sepharose. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis,
      B-SJA-II gave four bands: subunit a-1 (Mr = 19,400), a-2 (Mr = 18,200), b-1 (Mr =
      15,000), and b-2 (Mr = 13,200). Carbohydrate analysis and binding study with
      horseradish peroxidase-labeled lectins on the bands electroblotted onto
      polyvinylidene difluoride membrane showed that the three subunits other than b-2
      have N-linked oligosaccharides typical of plant glycoproteins. The binding assay
      with horseradish peroxidase-glycoproteins revealed that all the subunits can bind
      sugar specifically with fetuin and asialofetuin. Furthermore, B-SJA-II aggregated
      to form precipitates in the absence of a specific sugar and became soluble upon
      addition of the specific sugar. The results indicate that each subunit has a
      sugar-binding site for the mannosyl core of N-linked oligosaccharide chains and
      recognizes each other sugar specifically to form aggregates. According to the N
      terminal amino acid sequences obtained, the subunits are classified into two
      groups. The first group (a-1 and a-2) has an N-terminal sequence 50% identical
      with that of other S. japonica lectins (Hankins, C. N., Kindinger, J. I., and
      Shannon, L. M. (1988) Plant Physiol. 86, 67-70) and the amino acid sequence
      initiating at position 123 of concanavalin A (Cunningham, B. (1975) J. Biol.
      Chem. 250, 1503-1512), while the N-terminal sequence of the second group (b-1 and
      b-2) is homologous to that of concanavalin A, but completely different from that
      of the first group.

PMID- 1993687
TI  - Epidermal growth factor or okadaic acid stimulates phosphorylation of eukaryotic
      initiation factor 4F.
AB  - Eukaryotic initiation factor 4F, a multi-protein mRNA cap binding complex, was
      isolated by m7GTP-Sepharose affinity chromatography from human mammary epithelial
      cells (184A1N4) incubated with [32P] orthophosphate. Treatment of cells with
      epidermal growth factor resulted in enhanced phosphorylation of both p28 (eIF-4E)
      and p220 subunits. The identities of the p28 and p220 subunits were confirmed by
      immunoprecipitation. The phosphorylation was both rapid and sustained in
      duration; p28 attained maximal levels (2-3-fold) within 30 min of treatment and
      remained elevated for at least 2 h, while p220 reached one-half maximal levels by
      30 min, and maximal levels (3-4-fold) by 2 h of treatment. Two phosphorylated
      isoforms of p28 and multiple phosphorylated forms of p220 were detected by two
      dimensional isoelectric focusing/sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. Phosphoamino acid analysis of 6 N HCl hydrolyzates of p28 and
      p220 isolated from epidermal growth factor-treated and control cells indicated
      that serine is the predominant phosphorylated amino acid in both instances. In no
      case was phosphotyrosine observed. Pretreatment of cells with 1 microM okadaic
      acid resulted in the hyperphosphorylation of both p28 and p220 subunits. These
      results suggest that mitogenic growth factors and cellular serine/threonine
      phosphatases (pp1 and/or pp2A) serve essential roles in regulating
      phosphorylation levels of eukaryotic initiation factor 4F and support the concept
      that translational control is a component of the signal transduction mechanisms
      involved in growth regulation.

PMID- 1993688
TI  - A redox switch and phosphorylation are involved in the post-translational up
      regulation of the adenosine-uridine binding factor by phorbol ester and
      ionophore.
AB  - Messenger RNAs coding for cytokines and lymphokines are extremely unstable due to
      an AU-rich cis element located in their 3'-untranslated region. Cell activation
      with phorbol ester 12-O-tetradecanoylphorbol-13-acetate or calcium ionophore has
      been shown to markedly stabilize these normally labile messages. We have recently
      described a cytoplasmic protein, denoted the adenosine-uridine binding factor
      (AUBF) which complexes in vitro to a variety of labile RNAs containing multiple
      reiterations of the pentamer AUUUA. In order to determine if AUBF plays a role in
      the stabilization of cytokine and lymphokine mRNAs, we have investigated the
      mechanisms which control AUBF activity in peripheral blood mononuclear cells as
      well as Jurkat cells. AUBF is inactive in resting peripheral blood mononuclear
      cells but can be activated by brief treatment with 12-O-tetradecanoylphorbol-13
      acetate or ionophore. Up-regulation is independent of protein synthesis or RNA
      transcription, suggesting pre-existing AUBF is subject to post-translational
      modification. AUBF activity can be reversibly blocked by diamide but irreversibly
      inhibited by n-ethylmaleimide, suggesting that AUBF contains a redox switch as
      described for other RNA-binding proteins. Finally, AUBF activity is abolished by
      potato acid phosphatase, demonstrating that AUBF is a phosphoprotein. These data
      demonstrate that AUBF activity is subject to at least two levels of post
      translational regulation and is enhanced by mitogens previously shown to induce
      the stabilization of AUUUA mRNAs. Based upon these data, we propose that AUBF
      binding may mediate 12-O-tetradecanoylphorbol-13-acetate and ionophore-mediated
      labile message stabilization.

PMID- 1993689
TI  - The adenosine-uridine binding factor recognizes the AU-rich elements of cytokine,
      lymphokine, and oncogene mRNAs.
AB  - Selective mRNA degradation is an important control point in the transient
      expression of a variety of mRNAs coding for growth regulators. A variety of
      labile mRNAs coding for lymphokines, cytokines, and oncogenes contain within
      their 3'-untranslated region an AU-rich region shown to destabilize these
      messages. We recently identified a cytosolic protein, adenosine-uridine binding
      factor (AUBF), which complexes with four tandem AUUUA reiterations of a synthetic
      RNA transcript. We now show that AUBF forms RNase T1-resistant band-shifted
      complexes with a variety of in vitro transcribed mRNAs including granulocyte
      macrophage colony-stimulating factor, interferon-gamma, interleukin-3, c-fos, and
      v-myc. Formation of complexes was specifically inhibited by AUUUA containing RNA,
      but not by irrelevant RNA. After brief ultraviolet light-induced cross-linking,
      AUBF.RNA complexes with the exception of c-fos comigrated on sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis. Mutations within the AUUUA motifs
      demonstrate that both nucleotide sequence and secondary structure are important
      in AUBF.AUUUA RNA complex formation. Based upon these data, we suggest AUBF may
      interact with a variety of labile mRNAs with multiple AUUUA reiterations or
      single reiterations within an AU-rich 3'-untranslated region.

PMID- 1993690
TI  - Discharge effect on pancreatic exocrine secretion produced by toxins purified
      from Tityus serrulatus scorpion venom.
AB  - Three toxic polypeptides were purified from the venom of the Brazilian scorpion
      Tityus serrulatus by means of gel filtration in Sephadex G-50 and ion-exchange
      chromatography in carboxymethylcellulose. The peptides are basic molecules with
      molecular weights in the range of 7000 for which the amino acid compositions and
      sequences were determined. The effect of the purified peptides on pancreatic
      exocrine secretion in the guinea pig was studied. Biochemical measurements show
      that the cells are stimulated by these peptides to discharge their zymogen
      granules. Light and electron microscopic images confirm the biochemical
      measurements. At the light microscope level, acinar cells show dramatically fewer
      zymogen granules than in control pancreas with the appearance of large vacuoles
      and some loss of morphological integrity. Electron micrographs display apical
      regions devoid of zymogen granules and condensing vacuoles whereas acinar lumina
      contain crystalline secretory material. The secretory effect observed in vitro is
      comparable to that of carbamylcholine and that of the peptidergic secretagogue
      cholecystokinin-pancreozymin.

PMID- 1993691
TI  - Site-directed mutants, at position 166, of RTEM-1 beta-lactamase that form a
      stable acyl-enzyme intermediate with penicillin.
AB  - Class A beta-lactamases are known to hydrolyze substrates through a Ser70-linked
      acyl-enzyme intermediate, although the detailed mechanism remains unknown. On the
      basis of the tertiary structure of the active site, the role of Glu166 of class A
      enzymes was investigated by replacing the residue in RTEM-1 beta-lactamase with
      Ala, Asp, Gln, or Asn. All the mutants, in contrast to the wild-type, accumulated
      a covalent complex with benzylpenicillin which corresponds to an acyl-enzyme
      intermediate. For the Asp mutant, the complex decayed slowly and the hydrolytic
      activity was slightly retained both in vivo and in vitro. In contrast, the other
      mutants lost the hydrolytic activity completely and their complexes were stable.
      These results indicate that the side-chain carboxylate of Glu166 acts as a
      special catalyst for deacylation. Residues for deacylation have not been
      identified in other acyl enzymes, such as serine proteases and class C beta
      lactamases. Furthermore, the acyl-enzyme intermediates obtained are so stable
      that they are considered to be ideal materials for crystallographic studies for
      elucidating the catalytic mechanism in more detail. In addition, the mutants can
      more easily form inclusion bodies than the wild-type, when they are produced in a
      large amount, suggesting that the residue also plays an important role in proper
      folding of the enzyme.

PMID- 1993692
TI  - Recombinant interleukin-1 beta inhibits elastin formation by a neonatal rat lung
      fibroblast subtype.
AB  - The effect of recombinant interleukin-1 beta (rIL-1 beta) on elastin accumulation
      by lipid-laden interstitial cells (LIC) derived from neonatal rat lung was
      examined. The LIC, a fibroblast subtype, synthesized large amounts of elastin
      which was deposited into the extracellular matrix. This elastin was alkali
      resistant and had an amino acid composition typical of adult rat elastin.
      Treatment of lipid-laden interstitial cell cultures with rIL-1 beta at 100 pg/ml
      caused a dramatic decrease in elastin accumulation as assessed by hot alkali
      treatment and transmission electron micrographs of the cell cultures.
      Tropoelastin formation was selectively decreased by rIL-1 beta relative to other
      proteins. Steady state levels of elastin mRNA were slightly decreased by rIL-1
      beta at 5 pg/ml and markedly decreased by rIL-1 beta at 50 pg/ml or greater. The
      addition of indomethacin had no effect on rIL-1 beta-induced decreases in elastin
      mRNA levels. Inhibiting protein synthesis with cycloheximide blocked the effect
      of rIL-1 beta on elastin mRNA levels. The level of alpha 1(I) collagen mRNA was
      decreased by rIL-1 beta, but only at concentrations higher than that needed to
      induce a decrease in elastin mRNA. These data indicate that rIL-1 beta decreased
      steady state levels for elastin mRNA and elastin accumulation and can selectively
      regulate the accumulation of elastin and collagen.

PMID- 1993693
TI  - Spinach glycolate oxidase and yeast flavocytochrome b2 are structurally
      homologous and evolutionarily related enzymes with distinctly different function
      and flavin mononucleotide binding.
AB  - A comparison of the three-dimensional structures of the flavin mononucleotide
      (FMN)-dependent enzymes glycolate oxidase, flavocytochrome b2, and trimethylamine
      dehydrogenase is presented. Their flavin-binding domains all have the same
      structural motif, the 8-fold beta/alpha-barrel domain, which is also present in a
      large number of other enzymes. FMN is bound in a similar fashion in all three
      enzymes. The binding site is at the carboxyl-terminal end of the eight beta
      strands of the barrel where the active site is invariably found in this type of
      domain structure. The similarity of the structures of glycolate oxidase and
      flavocytochrome b2 extends to the loop regions and even outside the beta/alpha
      barrels with a root mean square deviation of 0.93 A for 311 superimposed C alpha
      atoms and with a sequence identity of 37%. A detailed analysis of their active
      sites shows, however, that the orientation of FMN is significantly different in
      the two structures due to different conformations of residues in the end of
      strand one. Thus, in flavocytochrome b2 a hydrogen bond is formed between the FMN
      N-5 position and the main chain amide of Ala-198, while in glycolate oxidase, the
      ring system is tilted away from the strand, creating a pocket on the re-side of
      the FMN ring where a water molecule is bound. Model building shows that this site
      could accommodate the hydroperoxide moiety of a FMN-4a-hydroperoxide
      intermediate. Thus, in the course of evolution, a few mutations in, and close to,
      the active sites have fine tuned these enzymes to exert their specific functions
      as an oxidase or transferase, respectively.

PMID- 1993694
TI  - Characterization by NMR of the heme-myoglobin adduct formed during the reductive
      metabolism of BrCCl3. Covalent bonding of the proximal histidine to the ring I
      vinyl group.
AB  - The reductive debromination of BrCCl3 by ferrous deoxymyoglobin leads to the
      covalent bonding of the prosthetic heme to the protein. We have previously shown,
      by the use of peptide mapping and mass spectrometry, that histidine residue 93 is
      covalently bound to the heme moiety. In the present study the structure of the
      heme adduct was more completely determined by 1H and 13C NMR techniques. We have
      found that the ring I vinyl group of the prosthetic heme was altered by the
      addition of a histidine imidazole nitrogen to the alpha-carbon and a CCl2 moiety
      to the beta-carbon. The electronic absorption spectra of the oxidized and reduced
      states of the altered heme-protein indicated that the heme-iron exists in a bis
      histidine-ligated form. Analysis of the crystal structure of native myoglobin
      suggested that for the altered heme-protein, histidine residues 97 and 64 are
      ligated to the heme-iron and that residue 97 has replaced the native proximal
      histidine residue 93. These movements, in effect a "histidine shuffle" at the
      active site, may be responsible for the enhanced reducing activity of the altered
      protein.

PMID- 1993695
TI  - Dissociation of protein kinase C activation and sn-1,2-diacylglycerol formation.
      Comparison of phosphatidylinositol- and phosphatidylcholine-derived diglycerides
      in alpha-thrombin-stimulated fibroblasts.
AB  - Diacylglycerols (DAGs) derived from phosphatidylcholine (PC) hydrolysis have been
      shown to activate protein kinase C (PKC) in vitro, but it is not known whether
      this event occurs in response to DAGs generated via agonist-induced PC hydrolysis
      in intact cells. In this report we have addressed this question directly, using
      alpha-thrombin stimulation of IIC9 fibroblasts. PKC activation in intact cells
      was assessed in two ways, by measuring: 1) PKC membrane association as determined
      by kinase activity and Western blot analysis and 2) the phosphorylation of an
      endogenous PKC substrate, an 80-kDa protein. Treatment with 500 ng/ml alpha
      thrombin has been shown to stimulate both phosphoinositide and PC hydrolysis,
      whereas treatment with 100 pg/ml alpha-thrombin stimulates only PC breakdown.
      Using these two conditions, we show that DAG produced from phosphoinositide, but
      not PC hydrolysis, is associated with the activation of PKC.

PMID- 1993696
TI  - Comparison of the physicochemical properties of type I and type II iodothyronine
      5'-deiodinase.
AB  - The 5'-deiodination of thyroxine is catalyzed by two enzymes which differ in
      their tissue distribution, substrate specificities, sensitivity to the inhibitor,
      propylthiouracil, and response to thyroid status. By using the affinity label, N
      bromoacetyl-L-thyroxine, both isoenzymes have been found to have substrate
      binding subunits of approximately 27 kDa. In this study, we compared the
      substrate binding subunits and hydrodynamic properties of the type I and the type
      II isozymes using the affinity label, N-bromoacetyl-L-thyroxine, to identify the
      enzymes. High resolution sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis showed that the substrate binding subunit of the type I enzyme
      had an Mr of 27,000, while that of the type II enzyme had a slightly higher Mr of
      29,000. This difference was not accounted for by glycosylation. Partial
      staphylococcal V8-protease digests of the substrate binding subunit of the type I
      enzyme yielded fragments of 14.6, 13.7, and 7.0 kDa, while V8-protease digests of
      the substrate binding subunit for the type II enzyme produced fragments of 28.0,
      25.1, 19.0, 9.5, 7.2, and 5.8 kDa. Unique cyanogen bromide fragmentation patterns
      were also observed for the two substrate binding subunits. Sedimentation
      coefficients of the detergent-soluble type I and type II holoenzymes were 3.67
      and 5.22 S, respectively, as determined by sucrose density centrifugation. The
      type I enzyme behaved as a globular protein, whereas the type II enzyme showed
      sedimentation properties typical of asymmetric integral membrane proteins. The
      Stokes radii were 3.78 and 4.97 nm, respectively. From these data, the calculated
      Mr for detergent-solubilized type I 5'-iodothyronine deiodinase was 55,400 and
      for the type II enzyme was 198,700. These data indicate that the two isozymes of
      iodothyronine 5'-deiodinase are multimeric, differ in holoenzyme size and subunit
      composition, and that their substrate binding subunits are distinct.

PMID- 1993697
TI  - CD63 antigen. A novel lysosomal membrane glycoprotein, cloned by a screening
      procedure for intracellular antigens in eukaryotic cells.
AB  - To clone the CD63 antigen, originally described as a blood platelet activation
      marker, we adapted the expression cloning procedure of Seed and Aruffo (Seed, B.,
      and Aruffo, A. (1987) Proc. Natl. Acad. Sci. U.S. A. 84, 3365-3369) to allow
      cloning of intracellular antigens. A megakaryocyte expression cDNA library was
      transiently transfected into MOP-8 mouse fibroblasts cultured on polyvinylidene
      difluoride membranes. Individual cells expressing intracellular CD63 were
      identified by autoradiography. cDNA was extracted from positive spots and
      reintroduced into Escherichia coli. After two screening rounds, a CD63 cDNA clone
      was isolated as assessed by immunofluorescence and Western blot analysis. The
      single long open reading frame of 238 amino acids contained four putative
      transmembrane regions and three N-glycosylation sites. The CD63 gene was
      expressed in a wide variety of cells. Surprisingly, CD63 was identical to ME491,
      an antigen reported as a melanoma-associated antigen (Hotta, H., Ross, A. H.,
      Huebner, K., Isobe, M., Wendeborn, S., Chao, M. V., Ricciardi, R. P., Tsujimoto,
      Y., Croce, C. M., and Koprowski, H. (1988) Cancer Res. 48, 2955-2962). By
      immunoelectron microscopy, co-localization with the lysosomal glycoproteins lamp
      1 and -2 identified CD63 as a novel lysosomal membrane glycoprotein. CD63 was not
      related to the lysosomal glycoprotein family but contained the putative lysosomal
      targeting signal Gly-Tyr in its short cytoplasmic tail.

PMID- 1993698
TI  - Fusion of sphingomyelin vesicles induced by proteins from Taiwan cobra (Naja naja
      atra) venom. Interactions of zwitterionic phospholipids with cardiotoxin
      analogues.
AB  - Egg sphingomyelin vesicles were used to assay aggregation/fusion activities of
      proteins from Taiwan (Naja naja atra) venom to avoid the problem of phospholipase
      A2 contamination during protein purification. It led to the identification of a
      new cardiotoxin (CTX) analogue protein (CTX V) with major aggregation/fusion, but
      few hemolysis, activities. On the contrary, cardiotoxin (CTX III) induced
      significant hemolysis of human red blood cells but exhibited few
      aggregation/fusion activities. To study the structure/activity relationship of
      these CTX-induced processes, the amino acid sequence of CTX V was determined and
      its aggregation/fusion activity was compared with that of CTX III by transmission
      electron microscopy, quasielastic laser light scattering, differential scanning
      calorimetry, and fluorescence spectroscopy. The results show that the CTX-induced
      fusion process at temperatures slightly above that of the gel to liquid
      crystalline phase transition of sphingomyelin vesicles can ultimately convert
      small sonicated vesicles into large fused vesicles with sizes of 1-2 microns. The
      abilities of CTX V to induce the leakage of sphingomyelin vesicles content and to
      cause the fusion of vesicles are approximately 10-fold higher than those of CTX
      III. Based on the CTX structures determined in the present and other studies, it
      is suggested that the amino acid residue X within the well conserved sequence of 
      Cys-Pro-X-Gly-Lys-Gln-Leu-Cys- plays a role in the interaction of CTX with lipid
      molecules. The lipid phase transition could further enhance the protein-lipid
      interaction in the process leading to the fusion of vesicles.

PMID- 1993699
TI  - Methionyl-tRNA synthetase gene from an extreme thermophile, Thermus thermophilus
      HB8. Molecular cloning, primary-structure analysis, expression in Escherichia
      coli, and site-directed mutagenesis.
AB  - The gene for the methionyl-tRNA synthetase (MetRS) from an extreme thermophile,
      Thermus thermophilus HB8, was cloned and sequenced. By expression of the T.
      thermophilus MetRS gene in Escherichia coli cells, thermostable MetRS was
      overproduced and purified to homogeneity by heat treatment and one-step column
      chromatography. The amino acid sequence of T. thermophilus MetRS showed low
      identities (approximately 25%) with those of MetRSs from E. coli, and cytoplasm
      and mitochondria of Saccharomyces cerevisiae. However, the amino acid residues in
      the binding sites for ATP and the anticodon and the 3' terminus of tRNA(Met) are
      highly conserved among the four MetRSs. T. thermophilus MetRS has a zinc finger
      like sequence with all the three cysteine residues and a histidine residue. By
      site-directed mutagenesis of one of the cysteine residues (Cys127) of T.
      thermophilus MetRS, the SH group was found to be important for methionyl-tRNA
      synthesis. Just upstream of the structural gene for T. thermophilus MetRS there
      is a short open reading frame which codes for a methionine-rich peptide and is
      partly overlapped with an alternative terminator/antiterminator structure,
      suggesting that transcription of this gene is regulated by attenuation. Further
      upstream a region contains a nucleotide sequence homologous to that of the 5'
      half of T. thermophilus initiator tRNA(Met).

PMID- 1993700
TI  - Conformational studies of the nucleic acid binding sites for Xenopus
      transcription factor IIIA.
AB  - The CD spectrum of a restriction fragment that contains a single copy of a
      Xenopus borealis somatic 5 S rRNA gene, like those of two smaller fragments from
      the binding site for transcription factor IIIA (TFIIIA), is that of B-form DNA.
      Under dehydrating conditions (76% ethanol) the 5 S rDNA undergoes a transition
      into an A conformation. The spectra of the three fragments, however, do exhibit
      some perturbation in that the longwave positive peaks are shifted to shorter
      wavelengths and have enhanced rotational strength compared with reference B-form
      spectra. The helical repeats measured for the smaller fragments indicate that the
      helix winding angle can account for these features in the CD spectra. We suggest
      that G:C-rich boxes that punctuate not only the TFIIIA binding site but the whole
      5 S gene are responsible for the conformational perturbation manifest in the CD
      spectra and may play a role in the recognition of the DNA by the factor. The
      spectrum of the gene is unchanged in the presence of TFIIIA, indicating that the
      structural heterogeneity of the DNA persists upon complex formation. The CD
      spectra of native TFIIIA.5 S rRNA particles isolated from oocytes and of
      particles reconstituted in vitro are identical and only moderately different from
      the spectrum of free 5 S rRNA, suggesting that the protein effects only limited
      changes in the secondary and/or tertiary structure of the RNA. The helical
      structure of the two binding sites is discussed with respect to a common mode of
      interaction of TFIIIA with DNA and RNA.

PMID- 1993701
TI  - Expression of carboxyl-terminally truncated forms of human apolipoprotein B in
      rat hepatoma cells. Evidence that the length of apolipoprotein B has a major
      effect on the buoyant density of the secreted lipoproteins.
AB  - We examined the relationship between the size of human apolipoprotein (apo) B and
      the formation and secretion of apoB-containing lipoprotein particles. Stable
      transformants of the rat hepatoma cell line McA-RH7777 harboring a variety of
      human apoB cDNA constructs were established, and these produced carboxyl
      terminally truncated apoB proteins (apoB18, -B23, -B28, -B31, -B48, and -B53).
      Immunoblotting of apoB proteins secreted into the culture medium and fractionated
      by equilibrium density ultracentrifugation revealed that each of the truncated
      apoB species was secreted from the cells. The peak densities of the apoB
      containing particles decreased as the length of the apoB proteins increased.
      Apolipoproteins B18 and B23 appeared at the bottom of the salt gradient (d = 1.23
      g/ml), whereas particles containing apoB28, -B31, -B37, -B48, and -B53 exhibited
      progressive decreases in density. The density distribution of secreted
      apolipoproteins was not affected by the expression or secretion of these
      recombinant apoB species. As determined by nondenaturing gel electrophoresis,
      apoB28, -B31, -B37, -B48, and -B53 formed their own discrete particles, and there
      was a direct correlation between the size of the particles and the length of the
      apoB species. The efficiency and rate of secretion of these truncated forms of
      apoB were studied by measuring the decrease of immunoprecipitated 35S-labeled
      apoB proteins in the cells and their accumulation in the medium. Proteins
      corresponding to apoB28 or larger were rapidly and efficiently secreted, whereas
      apoB18 and apoB23 were secreted much more slowly. These data imply that the size
      of these truncated apoB forms governs the lipid content of the apoB-containing
      lipoproteins formed as well as the kinetics of secretion.

PMID- 1993702
TI  - Characterization of a promoter element required for transcription in myocardial
      cells.
AB  - Transcription of the chicken cardiac troponin T (cTNT) gene in myocardial cells
      requires upstream sequences not required for expression of this gene in embryonic
      skeletal muscle cells. Deletion analysis shows that the segment between
      nucleotides -247 and -201 (numbered relative to the transcription initiation site
      at +1) is capable of conferring cardiac specific expression to a "minimal" cTNT
      promoter. The cardiac element within this segment contains at least two essential
      subregions: one residing upstream of position -215, which bears no homologies to
      known transcription elements, and an A/T-rich segment residing between positions 
      215 and -201. Conserved M-CAT motifs within the cTNT minimal promoter which are
      required for activity in skeletal muscle cells are also required for activity in
      myocardial cells, suggesting an interaction between the upstream cardiac element
      and proximal promoter elements. Gel-shift experiments demonstrate interaction
      between the upstream portion of the cardiac element and factor(s) present in the
      nuclei of cardiac and non-cardiac tissues. Thus, additional cis and trans factors
      are required for transcription of the cTNT gene in myocardial cells which are not
      required for expression in skeletal muscle cells.

PMID- 1993703
TI  - The glycine cleavage system. Occurrence of two types of chicken H-protein mRNAs
      presumably formed by the alternative use of the polyadenylation consensus
      sequences in a single exon.
AB  - Several cDNAs encoding H-protein, a constituent of the glycine cleavage system,
      were cloned from chicken liver cDNA libraries with an antibody raised against rat
      H-protein or with a nick-translated cDNA of an immunoreactive clone. The
      structure of the H-protein cDNA consisting of 910 base pairs was determined using
      clones with an apparent overlap in the nucleotide sequence. The cDNA encodes the
      precursor form of H-protein that is comprised of 39 amino acid residues for a
      mitochondrial presequence and 125 amino acid residues for the mature protein,
      following a 5' untranslated region of 13 base pairs. There are two genuine
      consensus sequences for the cleavage/polyadenylation of the precursor H-protein
      mRNA in the 3' untranslated region of the cDNA sequence. We showed by comparison
      with the delta-aminolevulinate synthase gene that only one copy of the H-protein
      cDNA occurs in the haploid genome of the chicken. Nevertheless, two types of H
      protein mRNAs, which differ by the length of their 3' untranslated region, are
      produced in liver. The chicken H-protein gene extends over 8 kilobase pairs on
      the genome and includes 5 exons that encode the entire cDNA sequence. Two AATAAA
      motifs are coded in the last exon of this gene, suggesting that the differently
      size H-protein mRNAs are produced by the alternative use of these motifs.

PMID- 1993704
TI  - The glycine cleavage system. Molecular cloning of the chicken and human glycine
      decarboxylase cDNAs and some characteristics involved in the deduced protein
      structures.
AB  - A cDNA encoding chicken glycine decarboxylase (pCP15b) was isolated using an
      antibody specific to this protein. Additional cDNAs were cloned with the aid of
      the genomic fragments obtained by using the pCP15b cDNA probe. No initiator
      methionine codon is found in the currently elucidated cDNA sequence, and an ATG
      codon in an exon is assigned to this role. The precursor glycine decarboxylase
      deduced from the 3514-base pair nucleotide sequence is comprised of 1,004 amino
      acids (Mr = 111,848). The 1,020 amino acid residues are encoded for the precursor
      form of human glycine decarboxylase (Mr = 112,869) in the 3,783-base long cDNA
      sequence of two 1.9-kilobase pair cDNAs with a pentanucleotide overlap. The
      pyridoxal phosphate binding site lysine and a glycine-rich region, which is
      suggested to be responsible for the attachment of the phosphate moiety of
      pyridoxal phosphate, are found in close proximity in both the chicken and human
      enzymes. This region essential for the enzyme action is suggested to be embedded
      in a segment rich in beta-turns and random coils and is surrounded by conserved
      and repetitive amino acid sequences. It is suggested that these structures are
      involved in the organization of the active site of glycine decarboxylase.

PMID- 1993705
TI  - The glycine cleavage system. The coupled expression of the glycine decarboxylase
      gene and the H-protein gene in the chicken.
AB  - Regulation of the transcription of the glycine decarboxylase gene and the H
      protein gene was examined in chicken. Northern analysis suggested and run-off
      transcription confirmed that the glycine decarboxylase gene transcription is
      exclusively tissue-specific and takes place at different efficiencies in liver,
      kidney, and brain which are the chicken tissues exhibiting the glycine cleavage
      activity. No evidence for the glycine decarboxylase gene transcription was
      obtained in heart, spleen, and skeletal muscle. Basal and tissue-specific
      transcription of the H-protein gene can be distinguished. The tissue-specific
      transcription coordinates with transcription of the glycine decarboxylase gene in
      active tissues, while low abundance H-protein and its mRNA, products of the basal
      transcription, exist in inactive tissues together with small amounts of T
      protein. Apparently, T-protein is synthesized by a process similar to that for H
      protein. Glycine decarboxylase mRNA levels show a linear relationship with H
      protein mRNA levels and with specific activities of the glycine cleavage reaction
      in active tissues. Tissue-specific distribution of the glycine cleavage activity
      is primarily determined by the expression of the glycine decarboxylase gene. The
      coordinate and tissue-specific transcription of the genes for the constituent
      proteins plays a key role in determining the magnitude of the glycine cleavage
      activity in chicken tissues and, thereby, the tissue-specificity of glycine
      metabolism.

PMID- 1993706
TI  - Signal peptide analogs derived from two chloroplast precursors interact with the
      signal recognition system of the chloroplast envelope.
AB  - We have used synthetic peptides representing segments of the signal sequences of
      preferredoxin (pFd) and the precursor of the small subunit of ribulose-1,5
      bisphosphate carboxylase (pS) to study interactions with the signal sequence
      recognition system at the chloroplast surface. Peptides representing the COOH
      terminal 30 amino acids of the pFd and pS signal peptides were able to completely
      and reversibly inhibit the import of their homologous precursors into isolated
      chloroplasts at a 2.5 microM concentration. Import was blocked at the level of
      precursor binding to the chloroplast. This inhibition of precursor binding and
      import was not due to disruption of chloroplast integrity as incubation of
      isolated chloroplasts with the peptides did not cause measurable perturbation of
      the envelope membranes. The peptides also were able to block the import of the
      heterologous precursor protein, suggesting that pS and pFd share a common signal
      sequence recognition system. Visualization of the bound peptides at the
      chloroplast surface by indirect immunofluorescence microscopy using antipeptide
      antibodies gave a marked punctate staining pattern. This pattern is consistent
      with the localization of chloroplast import receptor(s) at contact zones between
      the inner and outer envelope membranes.

PMID- 1993707
TI  - Hepatic endocytosis of various types of mannose-terminated albumins. What is
      important, sugar recognition, net charge, or the combination of these features.
AB  - We synthesized several para-aminophenyl (pap-) mannose-terminated albumins with
      varying sugar density (Man7-HSA, Man22-HSA, and Man40-HSA) and compared hepatic
      uptake with (thio-)mannose-terminated bovine serum albumin (Man-43-AI-BSA) The
      rate of uptake in isolated perfused rat livers was found to be positively
      correlated with the sugar density (Man40-HSA = Man22-HSA greater than Man7-HSA
      greater than HSA). Immunohistochemical staining of liver sections showed for both
      types of neoglycoproteins that uptake occurred in nonparenchymal cells only.
      Competition experiments with a 500-fold excess of mannan, a known ligand for the
      mannose/N-acetylglucosamine receptor, that is predominantly localized in
      endothelial cells, showed complete inhibition of the (thio-)Man43-AI-BSA uptake.
      In the case of (pap-)mannose-terminated albumins, however, the extent of
      inhibition by mannan was moderate and decreased markedly with increasing sugar
      density, being only 20% for (pap-)Man40-HSA. Therefore, we hypothesized that one
      or more additional removal systems contributed to the clearance of these (pap
      )mannose glycoproteins. We found that net negative charge of the (pap-)mannose
      albumins clearly increased with increasing sugar density, as shown on fast
      protein liquid chromatography anion-exchange chromatograms. To determine whether
      the scavenger receptor system that is also mainly present on endothelial cells is
      involved, we performed competition studies with strongly negatively charged
      substrates, such as dextran sulfate and formaldehyde-treated human serum albumin
      (fHSA). An excess of dextran sulfate (500 kDa), indeed blocked the (pap-)mannose
      albumin uptake for more than 95%. Dextran sulfate completely inhibited the
      hepatic uptake of mannan as well, indicating that the polyanion does not
      discriminate between the scavenger system and the mannose receptor system and
      should be regarded as an aspecific inhibitor of receptor-mediated endocytotic
      pathways. Surprisingly, a 500-fold excess of fHSA only moderately (20%) inhibited
      the clearance of (pap-)Man40-HSA in spite of its high affinity for the scavenger
      receptor. However, a combination of mannan and fHSA strongly inhibited the uptake
      of (pap-)Man22-HSA (90%) and to a lesser extent (pap-)Man40-HSA (80%), indicating
      that a third uptake mechanism may exist that recognizes both mannose groups (or
      other sugars) and net negative charge. This so far unnoticed receptor system
      apparently is strongly affected by dextran sulfate and, as shown by
      immunohistochemistry, is mainly localized on Kupffer cells rather than on the
      endothelial cells of the liver.

PMID- 1993708
TI  - Asn-linked oligosaccharide-dependent interaction between laminin and gp120/140.
      An alpha 6/beta 1 integrin.
AB  - Receptor-mediated recognition and adhesion to laminin, a specific glycoprotein
      from basement membranes, exert an important role in many biological phenomena.
      Studying cell surface proteins of B16-F10, a metastatic murine melanoma cell
      line, we identified a 120-140 kDa glycoprotein (gp120/140) that binds laminin.
      This glycoprotein was recognized by a polyclonal antibody raised against the
      human fibronectin receptor beta 1-integrin chain, as well as immunoprecipitated
      by an anti-alpha 6 chain (monoclonal antibody GoH3), characterizing it as an
      alpha 6/beta 1-integrin. Its binding to laminin was specific and displayed
      moderate affinity, as its apparent dissociation constant was 18 nM. To
      characterize the influence of carbohydrate moieties on the laminin-gp120/140
      interaction, metaperiodate oxidation, metabolic inhibition of glycosylation, and
      enzymatic deglycosylation studies were performed. Our results indicate that
      gp120/140 Asn-linked oligosaccharides play a part in this interaction.
      Reciprocally, both metaperiodate and N-glycanase treatment of native laminin
      reduced its binding to gp120/140, characterizing the latter as a lectin-like
      molecule. These results point to glycosylation processes as a possible mechanism
      for variable binding specificity profiles among integrins.

PMID- 1993709
TI  - Informed consent.

PMID- 1993710
TI  - Patients' recall of preoperative instruction for informed consent for an
      operation.
AB  - Thirty-eight consecutive patients who were admitted to the hospital for total
      joint replacement were studied to determine their understanding of the elements
      of informed consent at the time when they signed the consent document before the
      operation and their recall of those elements six months after the operation. All
      patients received instruction from the same patient-educator before the
      operation. Each patient was asked to respond verbally to a questionnaire about
      the preoperative instruction. If a question was not answered correctly, tutoring
      was given until the patient gave the correct response. The consent document was
      not presented for signature until the patient could answer all questions
      correctly. In an interview six months after the operation, thirty-six of the
      thirty-eight patients were asked the same questions that they had answered before
      the operation. The recall of risks and benefits six months after the operation
      was compared with the understanding of risks and benefits that had been
      demonstrated before the operation by both the verbal questioning and the signed
      consent document. At six months, the number of patients who recalled the risks
      ranged from nine (25 per cent) who remembered the risk of infection to only one
      who remembered the risk of damage to a nerve or artery. More patients recalled
      the potential benefits: eight (22 per cent) for relief of pain and improved
      function and five (16 per cent) for improved motion.

PMID- 1993711
TI  - Familial cervical dysplasia.
AB  - Nine of twelve family members from three generations were affected by an
      inherited form of cervical vertebral dysplasia. All of the affected people had an
      abnormality of the first cervical vertebra. Some also had defects of the axis and
      caudad to it. The mode of transmission of the disorder is autosomal dominant,
      with apparently complete penetrance and variable expressivity. Two patients had
      symptoms. One had a passively correctable tilt of the head, with an associated
      audible clunk and hypoplasia of the left superior facet of the second cervical
      vertebra. This patient had no local symptoms, neurological involvement, or muscle
      spasm. In the other patient, suboccipital pain developed. Radiographs revealed an
      anterior atlanto-occipital dislocation. The symptoms resolved after reduction and
      arthrodesis. Because of the apparently complete penetrance of this disorder,
      physicians caring for patients who have this type of congenital malformation of
      the cervical spine should consider examination of closely related members of the
      family. Clinical findings such as tilting of the head, torticollis, or limitation
      of cervical motion suggest that additional evaluation should be done. The
      examination should include lateral radiographs of the cervical spine in flexion
      and extension. Three-dimensional computed-tomography reformatting was helpful in
      demonstrating the complex cervical anatomy in our patients. Patients who have
      recognized abnormalities should be followed and should be re-examined whenever
      local or neurological symptoms develop. A magnetic resonance image of the spine
      in flexion and extension was valuable for identification of the potentially
      disastrous situation of impending damage to the cord in patients who had
      instability and evolving symptoms.

PMID- 1993712
TI  - Regeneration through nerve allografts in the cynomolgus monkey (Macaca
      fascicularis).
AB  - With the use of ulnar nerves of cynomolgus monkeys, the present study examined
      whether basal laminae of Schwann cells can serve as conduits for regenerating
      axons in nerve allografts from non-human primates. A segment of ulnar nerve was
      transected distal to the elbow joint one week before grafting. In Group A, a
      distal segment of the transected nerve was transplanted, after freezing and
      thawing, into the ulnar nerve of another monkey, at a level that corresponded to
      that from which the graft was taken. In Group B (the control group), the segment
      of nerve was grafted in the same manner but without cryotreatment. Two weeks,
      five weeks, eight weeks, and five months after grafting, the graft and the host
      nerve were examined with light and electron microscopy. Within two weeks after
      grafting in Group A, after degradation of the cellular components of the Schwann
      cells, the basal laminae of the Schwann cells were intact in the form of tubes.
      Within five weeks, many regenerating axons grew out into these basal lamina tubes
      in the three-centimeter-long grafts and extended into the host nerve. As seen at
      the wrist (seven centimeters from the distal suture) five months after grafting,
      the axons exhibited fully mature myelination both in the graft and in the host
      nerve. In contrast, in Group B, in which the Schwann cells had not been disrupted
      by cryotreatment, cellular components and connective-tissue matrices, including
      basal laminae, had been degraded and had been replaced by invading cells, which
      filled the endoneurial spaces of the graft. Five months after grafting, axonal
      growth had been arrested in the graft one centimeter distal to the proximal
      suture. The beneficial effect in Group A appears to have been the result of the
      retention and preservation of intact basal laminae of Schwann cells after rapid
      removal of killed Schwann cells and myelin debris. Killing of Schwann cells by
      freezing before grafting may abolish the immune response to the Schwann cells in
      allografts and lead to fragmentation and disruption of myelin, which facilitates
      the rapid removal of myelin by macrophages.

PMID- 1993713
TI  - Revision total knee arthroplasty for failed unicompartmental replacement.
AB  - The results in nineteen patients (twenty-one knees) who had a failed
      unicompartmental knee replacement followed by a revision total knee arthroplasty
      were evaluated. There were twelve excellent, four good, one fair, and two poor
      results. The interval between the unicompartmental replacement and the revision
      total knee arthroplasty ranged from eight months to eight years. At the time of
      the revision, a major osseous defect was found in sixteen knees (76 per cent).
      The duration of follow-up after the revision ranged from two to ten years. At the
      most recent follow-up examination, radiographs revealed at least one radiolucent
      line in thirteen knees (62 per cent). The technical difficulties associated with
      the revision operation are evidence that unicondylar arthroplasty is not a
      conservative procedure that allows a total knee arthroplasty to be done easily
      later. The results also do not support the argument that a revision performed
      after failure of a unicondylar arthroplasty is less technically demanding than
      one performed after a failed primary total knee arthroplasty.

PMID- 1993714
TI  - The role of venous hypertension in the pathogenesis of Legg-Perthes disease. A
      clinical and experimental study.
AB  - Thirty-two patients in whom Legg-Perthes disease apparently involved only one hip
      were examined with venography, measurement of intraosseous and intra-articular
      pressures, arthrography, and dynamic triphasic bone-imaging with 99mTc methylene
      diphosphonate. The arterial flow of blood in the affected femoral head was
      slightly decreased, but the difference from that on the normal side was not
      statistically significant. However, there was marked disturbance of the venous
      drainage in the diseased hip, elevated intraosseous pressure in the affected
      femoral neck, and increased intra-articular pressure in the involved hip compared
      with the normal side. An animal model was then created in twenty immature dogs,
      venous drainage was obstructed, and intraosseous pressure of the femoral head and
      neck was elevated by injection of four milliliters of semiliquid silicone into
      the femoral neck. In eleven of the dogs, areas of avascular necrosis resembling
      those associated with Legg-Perthes disease developed in the femoral head.

PMID- 1993715
TI  - The effects of in situ freezing on the anterior cruciate ligament. An
      experimental study in goats.
AB  - We developed an in situ freeze-thaw model designed to simulate an ideally placed
      and oriented autogenous graft of the anterior cruciate ligament. In this model,
      the anterior cruciate ligament was exposed, and the femoral insertion, tibial
      insertion, and body of the anterior cruciate ligament were frozen in situ with
      specially designed freezing probes. Freeze-thaw cycles were repeated five times.
      We used the technique in thirty-three mature goats to study the biological and
      biomechanical outcomes of the devitalized and devascularized anterior cruciate
      ligament at zero, six, and twenty-six weeks after treatment. Thus, the collagen
      fibers of the simulated autogenous graft remain in normal anatomical position and
      the simulated graft is fixed under physiological tension. At twenty-six weeks, no
      statistically significant differences were noted between treated and
      contralateral control (untreated) ligaments relative to anterior-posterior
      translation, maximum force to rupture, stiffness in the linear region of the
      force-length curve, modulus of elasticity in the linear region, strain to maximum
      stress, or maximum stress. The only statistically significant difference was an
      increase in cross-sectional area of the ligament. This increase was 22 and 42 per
      cent greater than that in the control ligaments at six weeks and six months. At
      six months, the ligaments in the control group had an average mid-cross-sectional
      area of 17.7 +/- 1.2 square millimeters and the ligaments in the experimental
      group, 25.2 +/- 3.1 square millimeters. Changes in the size and density of the
      collagen fibrils also were demonstrated at six months. These observations are in
      sharp contrast to our previous studies of replacement of the anterior cruciate
      ligament, in which an allograft of the ligament or an allograft supplemented with
      a 3M ligament augmentation device (LAD; 3M, St. Paul, Minnesota) was used. In
      those studies, an average reduction in maximum strength of 75 per cent for the
      allografts and 50 per cent for the allografts that had a ligament-augmentation
      device was found at one year. We concluded that devitalized, devascularized
      anterior cruciate ligaments do not lose strength if the anatomical position and
      the orientation of the collagen fibers are not altered.

PMID- 1993716
TI  - Chronic rupture of the Achilles tendon: a new technique of repair.
AB  - A new operative technique is described for the treatment of patients who have a
      rupture of the Achilles tendon. The large gap between the proximal and distal
      stumps of the Achilles tendon in seven patients was bridged by use of the tendon
      of the flexor digitorum longus as the graft. At the most recent follow-up
      examination (average follow-up, thirty-nine months; range, two to six years), the
      result was excellent or good in six patients and fair in one. Postoperatively,
      two patients needed an adjuvant procedure: one, a local rotation flap and the
      other, a split-thickness skin graft. Both patients had excellent restoration of
      function. The patient who had a fair result had a persistent limp and residual
      discomfort. There were no re-ruptures.

PMID- 1993717
TI  - Treatment of de Quervain tenosynovitis. A prospective study of the results of
      injection of steroids and immobilization in a splint.
AB  - In a prospective study of non-operative treatment of de Quervain tenosynovitis,
      ninety-nine wrists of ninety-five consecutively seen patients who had this
      diagnosis had an injection of one milliliter of a 1 per cent lidocaine solution
      and one milliliter of a suspension containing forty milligrams of
      methylprednisolone acetate. Twelve patients (twelve wrists) were lost to follow
      up. Of the remaining eighty-seven wrists, fifty-four (62 per cent) had a
      satisfactory outcome at a mean of eighteen months (minimum follow-up, twelve
      months). The duration of symptoms before treatment did not affect the outcome.
      The result in thirty-three wrists (38 per cent) was considered unsatisfactory.
      Thirty of these wrists were subsequently treated with operative release of the
      first dorsal compartment, and twenty-two (73 per cent) of the thirty were found
      to have a separate compartment for the extensor pollicis brevis. The prevalence
      of a separate compartment is significantly higher than that in the general
      population, as shown in anatomical studies of cadavera.

PMID- 1993718
TI  - Management of pseudarthrosis after arthrodesis of the spine for idiopathic
      scoliosis.
AB  - Sixty-three first, second, or third-time repairs of one or more pseudarthroses
      were done in fifty-one patients who had had an arthrodesis for idiopathic
      scoliosis. Forty-five of the patients were female and six were male. The average
      age was 30.2 years. The indications for the sixty-three repairs were pain (twenty
      five repairs), progression of the curve (sixteen), both pain and progression of
      the curve (twelve), and radiographic changes only (ten). Failure of the implant
      was identified before 27 per cent of the sixty-three procedures. The
      pseudarthroses were diagnosed an average of 2.8 years after the initial
      arthrodeses. Sixty-eight per cent of the defects were visible on plain
      radiographs preoperatively and 32 per cent were identified at operation. During
      the time between the original arthrodeses and the repairs of the pseudarthroses,
      the scolioses increased by a mean of 7 degrees and the kyphoses, by a mean of 10
      degrees. Harrington distraction was the most commonly used instrumentation
      (twenty-six [41 per cent] of the sixty-three procedures), and autogenous iliac
      bone was the most commonly used material for the graft (thirty-three [52 per
      cent] of the procedures).

PMID- 1993719
TI  - Valgus deformities of the feet and characteristics of gait in patients who have
      rheumatoid arthritis.
AB  - To investigate the cause of valgus deformity of the hindfoot in patients who have
      rheumatoid arthritis and to characterize the effects of the deformity on gait,
      two groups of patients were evaluated clinically, radiographically, and with gait
      analysis in the laboratory. Group 1 consisted of seven patients who had
      seropositive rheumatoid arthritis and normal alignment of the feet and Group 2,
      of ten patients who had rheumatoid arthritis and valgus deformity of the
      hindfoot. In Group 2, the disease was of longer duration and the feet were more
      painful than in Group 1. There was no evidence of muscular imbalance, equinus
      contracture, valgus deformity of the tibiotalar joint, or isolated deficiency of
      the tibialis posterior (such as weakness, tenosynovitis, or rupture of the
      tendon) that could have contributed to the development of the valgus deformity.
      In the patients who had valgus deformity, quantitated electromyography
      demonstrated that the intensity and duration of activity of the tibialis
      posterior was significantly increased, apparently in an effort to support the
      collapsing longitudinal arch of the foot. Gait studies revealed decreases in
      velocity, stride length, and single-limb-support time, as well as delayed heel
      rise in both groups, but the decreases were more marked in the patients who had
      valgus deformity. The results of this study suggest that valgus deformity of the
      hindfoot in rheumatoid patients results from exaggerated pronation forces on the
      weakened and inflamed subtalar joint. These forces are caused by alterations in
      gait secondary to symmetrical muscular weakness and the effort of the patient to
      minimize pain in the feet. Radiographs also suggested an association between the
      valgus deformity of the feet and valgus deformity of the knees in patients who
      have rheumatoid arthritis.

PMID- 1993720
TI  - The effect of section of the medial collateral ligament on force generated in the
      anterior cruciate ligament.
AB  - Ten fresh-frozen knees from cadavera were instrumented with a specially designed
      transducer that measures the force that the anterior cruciate ligament exerts on
      its tibial attachment. Specimens were subjected to tibial torque, anterior tibial
      force, and varus-valgus bending moment at selected angles of flexion of the knee
      ranging from 0 to 45 degrees. Section of the medial collateral ligament did not
      change the force generated in the anterior cruciate ligament by applied varus
      moment. When valgus moment was applied to the knee, force increased dramatically
      after section of the medial collateral ligament; the increases were greatest at
      45 degrees of flexion. Section of the medial collateral ligament had variable
      effects on the force generated in the anterior cruciate ligament during internal
      rotation but dramatically increased that generated during external rotation;
      these increases were greatest at 45 degrees. Section of the medial collateral
      ligament increased mean total torsional laxity by 13 degrees (at 0 degrees of
      flexion) to 20 degrees (at 45 degrees of flexion). Application of an anteriorly
      directed force to the tibia of an intact knee increased the force generated in
      the anterior cruciate ligament; this increase was maximum near the mid-part of
      the range of tibial rotation and minimum with external rotation of the tibia.
      Section of the medial collateral ligament did not change the force generated in
      the anterior cruciate ligament by straight anterior tibial pull near the mid-part
      of the range of tibial rotation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1993721
TI  - Cardiac arrest during hip arthroplasty with a cemented long-stem component. A
      report of seven cases.
AB  - Seven patients had a cardiac arrest during hip arthroplasty with a cemented long
      stem femoral component. Four patients died in the operating room, and three
      patients were successfully resuscitated. When the three survivors were eventually
      discharged from the hospital, they had no known permanent cardiac, pulmonary, or
      neurological sequelae. Factors that were common to all of the patients were
      advanced age, osteoporotic bone, a previously undisturbed intramedullary canal,
      and use of a long-stem femoral component and several batches of
      methylmethacrylate. Hip arthroplasty with a long-stem femoral component is
      associated with substantial risk in these patients. Excessive pressurization of
      cement should be avoided, and invasive hemodynamic monitoring should be used when
      the described conditions are present.

PMID- 1993722
TI  - Reconstruction of the chronically insufficient anterior cruciate ligament with
      the central third of the patellar ligament.
AB  - The results of reconstruction of the anterior cruciate ligament with the central
      third of the patellar ligament as a free, autogenous, non-vascularized graft were
      retrospectively reviewed at our institution. Eighty reconstructions in seventy
      nine patients were evaluated after a minimum of two years. In forty-eight (60 per
      cent) of the knees, the reconstruction was augmented with an extra-articular
      lateral sling of iliotibial band. The patients were evaluated with a physical
      examination, a KT-1000 arthrometer, radiographs, a subjective questionnaire, and
      a revision of the scale of The Hospital for Special Surgery for rating ligaments.
      Postoperatively, seventy-six (95 per cent) of the eighty knees no longer gave
      way, and the pivot-shift test was negative in sixty-seven (84 per cent) of the
      knees. The average score on the ligament-rating scale was 93 points. All of the
      patients who had clinical instability at the time of the most recent follow-up
      had associated ligamentous instability that had not been appreciated or addressed
      at the time of reconstruction. Arthrometric evaluation revealed that the laxity
      differed by three millimeters or less from that of the untreated knee in sixty
      (76 per cent) of the treated knees. In the patient who had bilateral
      reconstruction, the laxity was the same in both knees. Seventeen patients, who
      had more than three millimeters of translation, also had additional related
      ligamentous instability, most commonly posterolateral instability and
      insufficiency of the medial collateral ligament. We think that major associated
      ligamentous instability predisposes the reconstruction to failure and should be
      corrected in conjunction with the reconstruction.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1993723
TI  - Prosthetic arthroplasty of the knee after resection of a sarcoma in the proximal
      end of the tibia. A report of sixteen cases.
AB  - The results of a specific type of prosthetic reconstruction of the knee (total
      replacement arthroplasty) after resection of a sarcoma of the proximal part of
      the tibia in sixteen patients were retrospectively reviewed. The diagnosis was
      stage-IIB osteogenic sarcoma in nine patients, stage-IIB malignant fibrous
      histiocytoma in three patients, and stage-IB sarcoma of various types in four
      patients. The length of tibial resection ranged from 100 to 257 millimeters. Of
      the eleven patients who were available for functional examination (mean duration
      of follow-up, sixty-three months), three patients had an excellent result, seven
      had a good result, and one had a fair result. Of the five patients who were not
      available for functional testing, one who was doing well was lost to follow-up at
      eighty months, one had died of metastases at sixteen months, and three had had a
      secondary amputation for infection or for loosening of the prosthesis.

PMID- 1993724
TI  - Dedifferentiated chondrosarcoma. Report of an unusual case.

PMID- 1993725
TI  - Idiopathic muscular infarction in a diabetic patient. Report of a case.

PMID- 1993726
TI  - Treatment for acute tears of the lateral ligaments of the ankle. Operation, cast,
      or early controlled mobilization.

PMID- 1993727
TI  - Seasonal variation of slipped capital femoral epiphysis.

PMID- 1993728
TI  - Dural laceration occurring with burst fractures and associated laminar fractures.

PMID- 1993729
TI  - Cellular morphogenesis in the Saccharomyces cerevisiae cell cycle: localization
      of the CDC3 gene product and the timing of events at the budding site.
AB  - Budding cells of the yeast Saccharomyces cerevisiae possess a ring of 10-nm
      diameter filaments, of unknown biochemical nature, that lies just inside the
      plasma membrane in the neck connecting the mother cell to its bud. Electron
      microscopic observations suggest that these filaments assemble at the budding
      site coincident with bud emergence and disassemble shortly before cytokinesis
      (Byers, B. and L. Goetsch. 1976. J. Cell Biol. 69:717-721). Mutants defective in
      any of four genes (CDC3, CDC10, CDC11, or CDC12) lack these filaments and display
      a pleiotropic phenotype that involves abnormal bud growth and an inability to
      complete cytokinesis. We showed previously by immunofluorescence that the CDC12
      gene product is probably a constituent of the ring of 10-nm filaments (Haarer, B.
      and J. Pringle. 1987. Mol. Cell. Biol. 7:3678-3687). We now report the use of
      fusion proteins to generate polyclonal antibodies specific for the CDC3 gene
      product. In immunofluorescence experiments, these antibodies decorated the neck
      regions of wild-type and mutant cells in patterns suggesting that the CDC3 gene
      product is also a constituent of the ring of 10-nm filaments. We also used the
      CDC3-specific and CDC12-specific antibodies to investigate the timing of
      localization of these proteins to the budding site. The results suggest that the
      CDC3 protein is organized into a ring at the budding site well before bud
      emergence and remains so organized for some time after cytokinesis. The CDC12
      product appears to behave similarly, but may arrive at the budding site closer to
      the time of bud emergence, and disappear from that site more quickly after
      cytokinesis, than does the CDC3 product. Examination of mating cells and cells
      responding to purified mating pheromone revealed novel arrangements of the CDC3
      and CDC12 products in the regions of cell wall reorganization. Both proteins were
      present in normal-looking ring structures at the bases of the first zygotic buds.

PMID- 1993730
TI  - A distinct vesicle population targets membranes and pore complexes to the nuclear
      envelope in Xenopus eggs.
AB  - Extracts from Xenopus eggs capable of nuclear envelope assembly in vitro were
      fractionated by differential and density gradient centrifugation. Nuclear
      envelope assembly was found to require soluble components in the cytosol and two
      distinct particulate fractions, which we have called nuclear envelope precursor
      fractions A and B (NEP-A and NEP-B). Both NEP-A and NEP-B are sensitive to
      treatments with trypsin, sodium carbonate, and detergents, but can be
      distinguished from each other by their sensitivities to high salt and N
      ethylmaleimide and by their levels of alpha-glucosidase activity. Vesicles in NEP
      B bind to chromatin, whereas those in NEP-A do not. NEP-B may therefore be
      involved in the targeting of membranes to the surface of the chromatin, whereas
      NEP-A may provide a pool of vesicles that contributes many of the nuclear
      envelope membranes. NEP-B may also play a role in the assembly of nuclear pore
      complexes because the density of nuclear pores in the resulting envelope is
      dependent on the ratio of NEP-B to NEP-A in the reconstituted extract.

PMID- 1993731
TI  - The nuclear membrane determines the timing of DNA replication in Xenopus egg
      extracts.
AB  - We have exploited a property of chicken erythrocyte nuclei to analyze the
      regulation of DNA replication in a cell-free system from Xenopus eggs. Many
      individual demembranated nuclei added to the extract often became enclosed within
      a common nuclear membrane. Nuclei within such a "multinuclear aggregate" lacked
      individual membranes but shared the perimeter membrane of the aggregate.
      Individual nuclei that were excluded from the aggregates initiated DNA synthesis
      at different times over a 10-12-h period, as judged by incorporation of
      biotinylated dUTP into discrete replication foci at early times, followed by
      uniformly intense incorporation at later times. Replication forks were clustered
      in spots, rings, and horseshoe-shaped structures similar to those described in
      cultured cells. In contrast to the asynchronous replication seen between
      individual nuclei, replication within multinuclear aggregates was synchronous.
      There was a uniform distribution and similar fluorescent intensity of the
      replication foci throughout all the nuclei enclosed within the same membrane.
      However, different multinuclear aggregates replicated out of synchrony with each
      other indicating that each membrane-bound aggregate acts as an individual unit of
      replication. These data indicate that the nuclear membrane defines the unit of
      DNA replication and determines the timing of DNA synthesis in egg extract
      resulting in highly coordinated triggering of DNA replication on the DNA it
      encloses.

PMID- 1993732
TI  - Guanine nucleotides modulate the effects of brefeldin A in semipermeable cells:
      regulation of the association of a 110-kD peripheral membrane protein with the
      Golgi apparatus.
AB  - The release of a 110-kD peripheral membrane protein from the Golgi apparatus is
      an early event in brefeldin A (BFA) action, preceding the movement of Golgi
      membrane into the ER. ATP depletion also causes the reversible redistribution of
      the 110-kD protein from Golgi membrane into the cytosol, although no Golgi
      disassembly occurs. To further define the effects of BFA on the association of
      the 110-kD protein with the Golgi apparatus we have used filter perforation
      techniques to produce semipermeable cells. All previously observed effects of
      BFA, including the rapid redistribution of the 110-kD protein and the movement of
      Golgi membrane into the ER, could be reproduced in the semipermeable cells. The
      role of guanine nucleotides in this process was investigated using the
      nonhydrolyzable analogue of GTP, GTP gamma S. Pretreatment of semipermeable cells
      with GTP gamma S prevented the BFA-induced redistribution of the 110-kD protein
      from the Golgi apparatus and movement of Golgi membrane into the ER. GTP gamma S
      could also abrogate the observed release of the 110-kD protein from Golgi
      membranes which occurred in response to ATP depletion. Additionally, when the 110
      kD protein had first been dissociated from Golgi membranes by ATP depletion, GTP
      gamma S could restore Golgi membrane association of the 110-kD protein, but not
      if BFA was present. All of these effects observed with GTP gamma S in
      semipermeable cells could be reproduced in intact cells treated with AlF4-. These
      results suggest that guanine nucleotides regulate the dynamic
      association/dissociation of the 110-kD protein with the Golgi apparatus and that
      BFA perturbs this process by interfering with the association of the 110-kD
      protein with the Golgi apparatus.

PMID- 1993734
TI  - A stromal protein factor maintains the solubility and insertion competence of an
      imported thylakoid membrane protein.
AB  - The light-harvesting chlorophyll a/b protein (LHCP) is an approximately 25,000-D
      thylakoid membrane protein. LHCP is synthesized in the cytosol as a precursor and
      must translocate across the chloroplast envelope before becoming integrally
      associated with the thylakoid bilayer. Previous studies demonstrated that
      imported LHCP traverses the chloroplast stroma as a soluble intermediate before
      thylakoid insertion. Here, examination of this intermediate revealed that it is a
      stable, discrete approximately 120,000-D species and thus either an LHCP oligomer
      or a complex with another component. In vitro-synthesized LHCP can be converted
      to a similar form by incubation with a stromal extract. The stromal component
      responsible for this conversion is proteinaceous as evidenced by its inactivation
      by heat, protease, and NEM. Furthermore, the conversion activity coelutes from a
      gel filtration column with a stromal protein factor(s) previously shown to be
      necessary for LHCP integration into isolated thylakoids. Conversion of LHCP to
      the 120-kD form prevents aggregation and maintains its competence for thylakoid
      insertion. However, conversion to this form is apparently not sufficient for
      membrane insertion because the isolated 120-kD LHCP still requires stroma to
      complete the integration process. This suggests a need for at least one more
      stroma-mediated reaction. Our results explain how a hydrophobic thylakoid protein
      remains soluble as it traverses the aqueous stroma. Moreover, they describe in
      part the function of the stromal requirement for insertion into the thylakoid
      membrane.

PMID- 1993733
TI  - Spatial organization of the assembly pathways of glycoproteins and complex
      polysaccharides in the Golgi apparatus of plants.
AB  - The Golgi apparatus of plant cells is the site of assembly of glycoproteins,
      proteoglycans, and complex polysaccharides, but little is known about how the
      different assembly pathways are organized within the Golgi stacks. To study these
      questions we have employed immunocytochemical techniques and antibodies raised
      against the hydroxyproline-rich cell wall glycoprotein, extensin, and two types
      of complex polysaccharides, an acidic pectic polysaccharide known as
      rhamnogalacturonan I (RG-I), and the neutral hemicellulose, xyloglucan (XG). Our
      micrographs demonstrate that individual Golgi stacks can process simultaneously
      glycoproteins and complex polysaccharides. O-linked arabinosylation of the
      hydroxyproline residues of extensin occurs in cis-cisternae, and glycosylated
      molecules pass through all cisternae before they are packaged into secretory
      vesicles in the monensin-sensitive, trans-Golgi network. In contrast, in root tip
      cortical parenchyma cells, the anti-RG-I and the anti-XG antibodies are shown to
      bind to complementary subsets of Golgi cisternae, and several lines of indirect
      evidence suggest that these complex polysaccharides may also exit from different
      cisternae. Thus, RG-I type polysaccharides appear to be synthesized in cis- and
      medial cisternae, and have the potential to leave from a monensin-insensitive,
      medial cisternal compartment. The labeling pattern for XG suggests that it is
      assembled in trans-Golgi cisternae and departs from the monensin-sensitive trans
      Golgi network. This physical separation of the synthesis/secretion pathways of
      major categories of complex polysaccharides may prevent the synthesis of mixed
      polysaccharides, and provides a means for producing secretory vesicles that can
      be targeted to different cell wall domains.

PMID- 1993735
TI  - Three different actin filament assemblies occur in every hair cell: each contains
      a specific actin crosslinking protein.
AB  - The apex of hair cells of the chicken auditory organ contains three different
      kinds of assemblies of actin filaments in close spatial proximity. These are (a)
      paracrystals of actin filaments with identical polarity in stereocilia, (b) a
      dense gellike meshwork of actin filaments forming the cuticular plate, and (c) a
      bundle of parallel actin filaments with mixed polarities that constitute the
      circumferential filament belt attached to the cytoplasmic aspect of the zonula
      adhaerens (ZA). Each different supramolecular assembly of actin filaments
      contains a specific actin filament cross-linking protein which is unique to that
      particular assembly. Thus fimbrin appears to be responsible for paracrystallin
      packing of actin filaments in stereocillia; an isoform of spectrin resides in the
      cuticular plate where it forms the whisker-like crossbridges, and alpha actinin
      is the actin crosslinking protein of the circumferential ZA bundle. Tropomyosin,
      which stabilizes actin filaments, is present in all the actin filament assemblies
      except for the stereocilia. Another striking finding was that myosin appears to
      be absent from the ZA ring and cuticular plate of hair cells although present in
      the ZA ring of supporting cells. The abundance of myosin in the ZA ring of the
      surrounding supporting cells means that it may be important in forming a
      supporting tensile cellular framework in which the hair cells are inserted.

PMID- 1993737
TI  - Immunolocalization and molecular properties of a high molecular weight
      microtubule-bundling protein (syncolin) from chicken erythrocytes.
AB  - A protein of apparent molecular weight 280,000 (syncolin), which is
      immunoreactive with antibodies to hog brain microtubule-associated protein (MAP)
      2, was purified from chicken erythrocytes. Immunofluorescence microscopy of bone
      marrow cells revealed the presence of syncolin in cells at all stages of
      erythrocyte differentiation. In early erythroblasts syncolin was diffusely
      distributed throughout the cytoplasm. At later stages it was found along
      microtubules of the marginal band, as confirmed by immunoelectron microscopy. The
      association of syncolin with the marginal band was dependent on the integrity of
      microtubules, as demonstrated by temperature-dependent de- and repolymerization
      or marginal band microtubules. Syncolin cosedimented in a saturable manner with
      microtubules assembled in vitro, and it was displaced from the polymer by salt.
      Brain as well as erythrocyte microtubules, reconstituted with taxol from MAP-free
      tubulin and purified syncolin, were aggregated into dense bundles containing up
      to 15 microtubules, as determined by electron microscopy. On the ultrastructural
      level, syncolin molecules were visualized as globular or ringlike structures, in
      contrast to the thin, threadlike appearance of filamentous MAPs, such as brain
      MAP 2. According to ultrastructural measurements and gel permeation
      chromatography, syncolin's molecular weight was approximately 1 x 10(6). It is
      suggested that syncolin's specific function is the cross-linking of microtubules
      in the marginal band and, by implication, the stabilization of this structure
      typical for nucleated (chicken) erythrocytes.

PMID- 1993736
TI  - Beta actin and its mRNA are localized at the plasma membrane and the regions of
      moving cytoplasm during the cellular response to injury.
AB  - Previous work in our laboratory has shown that microvascular pericytes sort
      muscle and nonmuscle actin isoforms into discrete cytoplasmic domains (Herman, I.
      M., and P. A. D'Amore. 1985. J. Cell Biol. 101:43-52; DeNofrio, D.T.C. Hoock, and
      I. M. Herman. J. Cell. Biol. 109:191-202). Specifically, muscle (alpha-smooth)
      actin is present on the stress fibers while nonmuscle actins (beta and gamma) are
      located on stress fibers and in regions of moving cytoplasm (e.g., ruffles,
      lamellae). To determine the form and function of beta actin in microvascular
      pericytes and endothelial cells recovering from injury, we prepared isoform
      specific antibodies and cDNA probes for immunolocalization, Western and Northern
      blotting, as well as in situ hybridization. Anti-beta actin IgG was prepared by
      adsorption and release of beta actin-specific IgG from electrophoretically
      purified pericyte beta actin bound to nitrocellulose paper. Anti-beta actin IgGs
      prepared by this affinity selection procedure showed exclusive binding to beta
      actin present in crude cell lysates containing all three actin isoforms. For
      controls, we localized beta actin as a bright rim of staining beneath the
      erythrocyte plasma membrane. Anti-beta actin IgG, absorbed with beta actin bound
      to nitrocellulose, failed to stain erythrocytes. Simultaneous localization of
      beta actin with the entire F-actin pool was performed on microvascular pericytes
      or endothelial cells and 3T3 fibroblasts recovering from injury using anti-beta
      actin IgG in combination with fluorescent phalloidin. Results of these
      experiments revealed that pericyte beta actin is localized beneath the plasma
      membrane in association with filopods, pseudopods, and fan lamellae.
      Additionally, we observed bright focal fluorescence within fan lamellae and in
      association with the ends of stress fibers that are preferentially associated
      with the ventral plasmalemma. Whereas fluorescent phalloidin staining along the
      stress fibers is continuous, anti-beta actin IgG localization is discontinuous.
      When injured endothelial and 3T3 cells were stained through wound closure, we
      localized beta actin only in motile cytoplasm at the wound edge. Staining
      disappeared as cells became quiescent upon monolayer restoration. Appearance of
      beta actin at the wound edge correlated with a two- to threefold increase in
      steady-state levels of beta actin mRNA, which rose within 15-60 min after injury
      and returned to noninjury levels during monolayer restoration. In situ
      hybridization revealed that transcripts encoding beta actin were localized at the
      wound edge in association with the repositioned protein. Results of these
      experiments indicate that beta actin and its encoded mRNA are polarized at the
      membrane-cytoskeletal interface within regions of moving cytoplasm.

PMID- 1993738
TI  - Intracellular free calcium oscillates during cell division of Xenopus embryos.
AB  - In Xenopus embryos, previous results failed to detect changes in the activity of
      free calcium ions (Ca2+i) during cell division using Ca2(+)-selective
      microelectrodes, while experiments with aequorin yielded uncertain results
      complicated by the variation during cell division of the aequorin concentration
      to cell volume ratio. We now report, using Ca2(+)-selective microelectrodes, that
      cell division in Xenopus embryos is accompanied by periodic oscillations of the
      Ca2+i level, which occur with a periodicity of 30 min, equal to that of the cell
      cycle. These Ca2+i oscillations were detected in 24 out of 35 experiments, and
      had a mean amplitude of 70 nM, around a basal Ca2+i level of 0.40 microM. Ca2+i
      oscillations did not take place in the absence of cell division, either in
      artificially activated eggs or in cleavage-blocked embryos. Therefore, Ca2+i
      oscillations do not represent, unlike intracellular pH oscillations (Grandin, N.,
      and M. Charbonneau. J. Cell Biol. 111:523-532. 1990), a component of the basic
      cell cycle ("cytoplasmic clock" or "master oscillator"), but appear to be more
      likely related to some events of mitosis.

PMID- 1993740
TI  - The structure of plasmodesmata as revealed by plasmolysis, detergent extraction,
      and protease digestion.
AB  - Plasmodesmata or intercellular bridges that connect plant cells are cylindrical
      channels approximately 40 nm in diameter. Running through the center of each is a
      dense rod, the desmotubule, that is connected to the endoplasmic reticulum of
      adjacent cells. Fern, Onoclea sensibilis, gametophytes were cut in half and the
      cut surfaces exposed to the detergent, Triton X 100, then fixed. Although the
      plasma membrane limiting the plasmodesma is solubilized partially or completely,
      the desmotubule remains intact. Alternatively, if the cut surface is exposed to
      papain, then fixed, the desmotubule disappears, but the plasma membrane limiting
      the plasmodesmata remains intact albeit swollen and irregular in profile.
      Gametophytes were plasmolyzed, and then fixed. As the cells retract from their
      cell walls they leave behind the plasmodesmata still inserted in the cell wall.
      They can break cleanly when the cell proper retracts or can pull away portions of
      the plasma membrane of the cell with them. Where the desmotubule remains intact,
      the plasmodesma retains its shape. These images and the results with detergents
      and proteases indicate that the desmotubule provides a cytoskeletal element for
      each plasmodesma, an element that not only stabilizes the whole structure, but
      also limits its size and porosity. It is likely to be composed in large part of
      protein. Suggestions are made as to why this structure has been selected for in
      evolution.

PMID- 1993741
TI  - Nineteenth Annual International Neuropsychological Society Meeting. February 13
      16, 1991, San Antonio, Texas, USA. Program and abstracts.

PMID- 1993739
TI  - Low viscosity in the aqueous domain of cell cytoplasm measured by picosecond
      polarization microfluorimetry.
AB  - Information about the rheological characteristics of the aqueous cytoplasm can be
      provided by analysis of the rotational motion of small polar molecules introduced
      into the cell. To determine fluid-phase cytoplasmic viscosity in intact cells, a
      polarization microscope was constructed for measurement of picosecond anisotropy
      decay of fluorescent probes in the cell cytoplasm. We found that the rotational
      correlation time (tc) of the probes, 2,7-bis-(2-carboxyethyl)-5-(and-6
      )carboxyfluorescein (BCECF), 6-carboxyfluorescein, and 8-hydroxypyrene-1,3,6
      trisulfonic acid (HPTS) provided a direct measure of fluid-phase cytoplasmic
      viscosity that was independent of probe binding. In quiescent Swiss 3T3
      fibroblasts, tc values were 20-40% longer than those in water, indicating that
      the fluid-phase cytoplasm is only 1.2-1.4 times as viscous as water. The
      activation energy of fluid-phase cytoplasmic viscosity was 4 kcal/mol, which is
      similar to that of water. Fluid-phase cytoplasmic viscosity was altered by less
      than 10% upon addition of sucrose to decrease cell volume, cytochalasin B to
      disrupt cell cytoskeleton, and vasopressin to activate phospholipase C.
      Nucleoplasmic and peripheral cytoplasmic viscosities were not different. Our
      results establish a novel method to measure fluid-phase cytoplasmic viscosity,
      and indicate that fluid-phase cytoplasmic viscosity in fibroblasts is similar to
      that of free water.

PMID- 1993743
TI  - Evaluation of the Sceptor system for identification of bacteria of veterinary
      origin.
AB  - The Sceptor system (Becton Dickinson Diagnostic Instrument Systems, Towson Md.)
      was assessed for its ability to identify veterinary clinical isolates. A total of
      605 bacteria, including 315 isolates of the family Enterobacteriaceae, 191 gram
      negative nonenteric bacteria, and 99 gram-positive bacteria, were tested.
      Overall, 534 (88.3%) were correctly identified, 28 (4.6%) were not identified, 12
      (2.0%) were incorrectly identified at the genus levels, and 32 (5.3%) were
      incorrectly identified at the species level. The Sceptor system correctly
      identified 292 (92.7%) isolates of Enterobacteriaceae, 165 (86.4%) gram-negative
      nonenteric bacteria, and 77 (77.8%) gram-positive bacteria. One hundred thirty
      organisms not contained in the data base were tested with the Sceptor system to
      assess the possibility of expanding the data base. The Sceptor system was an
      acceptable method for the identification of isolates of Enterobacteriaceae but
      not gram-negative nonenteric and gram-positive bacteria of animal origin.
      Development of a veterinary isolate-specific data base would improve the utility
      of the Sceptor system in veterinary diagnostic bacteriology.

PMID- 1993742
TI  - Geographical and temporal distribution of babesial infection in Connecticut.
AB  - Human babesiosis was first recognized in Connecticut in 1989, nearly 15 years
      after Lyme disease, a similarly transmitted spirochetosis, was detected in the
      state. To determine the seroprevalence for the babesial pathogen and whether it
      was recently introduced, we used an indirect immunofluorescence assay to test for
      Babesia microti antibody in 1,285 Connecticut residents. Four groups were
      studied: I, people seropositive for Lyme disease, tested from 1986 to 1989; II,
      randomly selected outpatients tested in 1989; III, college students residing in
      Connecticut, tested from 1959 to 1989; and IV, healthy people without tick
      exposure or Lyme disease, tested in 1989. Babesia seropositivity was
      significantly higher in group I (9.5%; n = 735) than in groups II (2.6%; n = 304,
      P less than 0.0001) and III (1.0%; n = 206, P less than 0.0001) but not group IV
      (2.5%, n = 40). Babesia seropositivity for group I ranged from 9.2 to 10.2%
      between 1986 and 1989, and Babesia seropositivity for group III ranged from 0%
      between 1959 and 1985 to 2.9% between 1986 and 1989. There is a considerable risk
      of babesial infection among residents of the Connecticut mainland who are
      seropositive for Lyme disease, a risk that appears to have remained constant over
      the past 5 years.

PMID- 1993744
TI  - Quantitative antimicrobial susceptibility testing of Haemophilus influenzae and
      Streptococcus pneumoniae by using the E-test.
AB  - The E-test (PDM Epsilometer; AB Biodisk, Solna, Sweden) is an antimicrobial agent
      gradient-coated plastic test strip which allows MIC determinations on agar media.
      The test is performed in a manner similar to the agar disk diffusion procedure. A
      collection of Haemophilus influenzae and Streptococcus pneumoniae strains
      possessing various resistance mechanisms was used to evaluate the E-test method.
      H. influenzae strains were tested with both Haemophilus test medium (HTM) and PDM
      ASM II chocolate agar, while the S. pneumoniae strains were tested on Mueller
      Hinton sheep blood agar. E-test MICs for a total of 10 antimicrobial agents were
      compared with broth microdilution MICs determined according to National Committee
      for Clinical Laboratory Standards methods. In general, E-test MICs for both
      species were quickly and easily interpreted and agreed within one log2 MIC
      increment in 89.8% of tests with H. influenzae and in 80.4% of pneumococcal
      tests. The majority of disagreements between the E-test and conventional MICs
      occurred with trimethoprim-sulfamethoxazole because of trailing and diffuse E
      test MIC endpoints with both species. Ampicillin MICs for beta-lactamase
      producing H. influenzae determined by the E-test differed at times from those
      determined by conventional testing because of the vagaries of interpreting
      colonies growing within the E-test inhibition ellipses. E-test penicillin MICs
      for pneumococci tended to be 1 to 2 log2 dilutions lower than those determined by
      using Mueller-Hinton broth supplemented with lysed horse blood. Nevertheless,
      strains of both species with documented resistance to the study drugs were
      detected by E-tests, i.e., 0.7% of the tests had very major errors with H.
      influenzae and 0.8% had very major errors with S. pneumoniae. Thus, the E-test
      represents a potential alternative method for antimicrobial susceptibility
      testing of these two fastidious bacterial species.

PMID- 1993745
TI  - Nosocomial transmission of respiratory syncytial virus in immunocompromised
      adults.
AB  - Respiratory syncytial virus (RSV) isolates obtained from nine infected
      immunocompromised adult patients hospitalized during two consecutive winters
      (January through April 1987 and 1988) were collected and analyzed against a panel
      of monoclonal antibodies by an enzyme immunoassay. The history of the patients'
      illness, onset of symptoms, and date of initial isolation of virus was correlated
      with the hospital ward and time of hospitalization. Three patients died of
      respiratory failure related to RSV infection acquired nosocomially. A cluster of
      RSV disease in four patients hospitalized simultaneously during the 1987 season
      was demonstrated to be caused by four antigenically distinct viruses; despite an
      epidemiologic link among the patients, each had been infected from a different
      source. The RSV disease in the five immunocompromised adults in 1988 was caused
      by two distinct strains; three patients were infected with RSV subgroup A/4, and
      two were infected with RSV subgroup B/2. Combining the epidemiologic and strain
      characterization studies, none of four patients in 1987 were infected from each
      other, and two of five patients in 1988 may have been infected, directly or
      indirectly, from one of the other five. The strain characterization studies
      demonstrated the potential complexity of RSV nosocomial transmission and the need
      to consider a number of sources for transmission in developing effective
      prevention strategies. The three deaths underscore the importance of nosocomial
      RSV disease and the importance of effective prevention strategies.

PMID- 1993747
TI  - Description and evaluation of the semiautomated 4-hour ATB 32E method for
      identification of members of the family Enterobacteriaceae.
AB  - A study was performed to compare the rapid identification system ATB 32E (API
      bioMerieux SA, La Balme-les-Grottes, France) with conventional biochemical
      methods for identifying 414 isolates of the family Enterobacteriaceae and the
      genus Aeromonas, mainly of clinical origin. Overall, 395 strains (95.4%) were
      correctly identified, with 48 (11.6%) requiring extra tests for complete
      identification. Ten strains (2.4%) were not identified, and nine (2.9%) were
      misidentified. The ATB 32E is a suitable alternative for rapid identification of
      members of the family Enterobacteriaceae.

PMID- 1993746
TI  - Evaluation of practical chromatographic procedures for identification of clinical
      isolates of mycobacteria.
AB  - After experimental conditions were established, 366 strains of mycobacteria
      belonging to 23 different species were studied for fatty acids, secondary
      alcohols, and mycolic acid cleavage products by capillary gas-liquid
      chromatography. Additionally, the mycolic acid pattern was studied by thin-layer
      chromatography. Capillary gas-liquid chromatography allowed direct identification
      of the following Mycobacterium spp.: M. kansasii, M. marinum, M. szulgai, M.
      xenopi, M. malmoense, and M. gordonae. The patterns of mycolic acid methyl esters
      recorded for the test strains of M. chelonae and M. agri may be of value in the
      identification of these species. Moreover, the combined use of the two
      chromatographic techniques provided precise identification of the M. tuberculosis
      complex, M. simiae, M. fallax, M. triviale, and M. chelonae-like organisms. A
      minimal set of biochemical tests is usually required to obtain identification to
      the species level when chromatographic procedures alone are not sufficient. Under
      the reported experimental conditions, thin-layer chromatography and capillary gas
      liquid chromatography are rapid and very useful techniques for the identification
      of mycobacteria.

PMID- 1993748
TI  - Enzyme-linked immunoassay for human immunodeficiency virus type 1 envelope
      glycoprotein 120.
AB  - An enzyme-linked immunosorbent assay (ELISA) that can measure picogram quantities
      of human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein 120 (gp120)
      in cell culture medium or body fluids has been developed. Recombinant, soluble
      CD4 immobilized in microtiter trays was used to capture gp120, which was then
      detected with polyclonal sheep antibody to gp120 followed by biotinylated rabbit
      anti-sheep immunoglobulin G and an avidin-alkaline phosphatase indicator system.
      With a reference recombinant gp120, the assay showed a linear relationship
      between optical density and concentrations ranging from 60 to 6,000 pg/100
      microliters well; precision of the assay varied with the concentrations and
      ranged from +/- 40% with amounts smaller than 200 pg to +/- 10% with amounts
      larger than 200 pg. In a group of coded samples containing 60 pg (approximately
      10(7) molecules) of reference gp120, the assay correctly identified the samples
      as containing gp120 99% of the time, with no false-positive results recorded for
      blank samples. Recombinant gp120 prepared in another cell culture system
      demonstrated a binding coefficient 13-fold lower than that of reference gp120.
      Mixing standard amounts of reference gp120 with increasing concentrations of
      human sera reduced assay sensitivity, although the linear relationship between
      gp120 concentration and optical density remained. With this assay we were able to
      detect gp120 in HIV-1 suspensions prepared from cultured lymphoblastoid cells and
      in the sera of HIV-1-infected patients. This ELISA for gp120 should be useful for
      studying the biological role of gp120 in HIV infection.

PMID- 1993749
TI  - Laboratory investigations on the low pathogenic potential of Plesiomonas
      shigelloides.
AB  - The pathogenic properties of 16 Plesiomonas shigelloides strains recovered from
      humans with extraintestinal and intestinal illnesses, infected animals, and
      environmental sources were investigated. Most strains possessed a high cell
      charge and low surface hydrophobicity analogous to those of Shigella spp.;
      additionally, serogroup O:17 strains reacted with Shigella group D antisera.
      However, unlike the shigellae, P. shigelloides strains did not universally bind
      Congo red, were noninvasive in HEp-2 cell assays, and did not produce a Shiga
      like toxin on Vero cells. On HEp-2, Y1, and possibly Vero cells, a low-level
      cytolysin was consistently produced by all 16 P. shigelloides strains when grown
      in either Evan Casamino Acids-yeast extract or Penassay broth. The median 50%
      lethal dose for all 16 P. shigelloides strains in outbred Swiss Webster mice was
      3.5 x 10(8) CFU (range, 3.2 x 10(7) to greater than 1 x 10(9) CFU). Animal
      pathogenicity did not correlate with cytolysin expression, possession of a
      greater than or equal to 120-MDa plasmid, protein profile, or resistance to
      complement-mediated lysis. No strain analyzed produced siderophores or a heat
      stable enterotoxin. The results suggest that members of the genus Plesiomonas
      have an overall low pathogenic potential, irrespective of the site of isolation
      or phenotypic, serologic, or surface properties shared with other traditional
      enteropathogens.

PMID- 1993750
TI  - Improved method for the routine identification of toxigenic Escherichia coli by
      DNA amplification of a conserved region of the heat-labile toxin A subunit.
AB  - This report describes a DNA amplification procedure for routine identification of
      heat-labile-toxin-producing Escherichia coli. Two oligonucleotide primers were
      used in a polymerase chain reaction procedure to amplify a highly conserved
      region of the A subunit of the heat-labile enterotoxin gene. Amplifications were
      done directly on E. coli colonies from plates when Salmonella, Shigella, or
      parasite infections were excluded as agents of the severe diarrhea in the
      patients. The conditions for the polymerase chain reaction method were
      empirically determined, and the procedure is inexpensive, sensitive, and
      specific. Positive results can be obtained over a wide variation in bacterial
      numbers, with no inhibition of Thermus aquaticus DNA polymerase. Detection of the
      amplified product can be done by agarose gel electrophoresis, which is specific
      and sensitive enough for routine diagnosis of this pathogen in clinical isolates.
      If greater sensitivity and specificity are required, hybridization with 32P- or
      alkaline phosphatase-labeled oligonucleotide probes can be used. Our results
      suggest that heat-labile-toxin-producing E. coli is responsible for about 9% of
      nondiagnosed diarrhea cases in Tygerberg Hospital, Tygerberg, Republic of South
      Africa.

PMID- 1993751
TI  - Interlaboratory comparison of titers of antibody to Borrelia burgdorferi and
      evaluation of a commercial assay using canine sera.
AB  - Sixty canine serum samples were sent to 10 different diagnostic laboratories for
      anti-Borrelia burgdorferi antibody analysis. All laboratories knew of the study
      prior to receiving the samples. Agreement among all laboratories for all
      interpretations was 91% (546 of 600 samples). There was complete agreement among
      all the laboratories for only 32 (53%) of the samples. Most of the disagreements
      were due to differences reported by either one (15 samples) or two (7 samples)
      laboratories per sample. When discrepancies in interpretations existed, the
      interpretation reported by the majority of the laboratories was considered the
      standard for comparison. One laboratory had no discrepant interpretations from
      this standard, while the laboratory with the most discrepancies had 16. The
      median number of discrepancies per laboratory was five. By using pairwise
      comparisons between each laboratory and the majority standard, eight of the
      laboratories showed strong agreement and the remaining two showed fair to good
      agreement. The type of test used (enzyme-linked immunosorbent assay versus
      indirect immunofluorescence assay) did not appear to influence the number of
      discrepant interpretations reported. Sera considered to be positive by the
      majority of the laboratories usually reacted to more than five antigens in
      immunoblots, with at least three or more of those being intense reactions. For
      positive samples, reactivity was consistently present in the 60-, 41-, 31-, and
      22- or 24-kDa regions. Samples considered negative usually reacted to fewer than
      three bands, with reactivity usually being faint. A commercially available, rapid
      dot blot assay showed strong agreement with the majority standard.

PMID- 1993752
TI  - A single-season epidemic with respiratory syncytial virus subgroup B2 during 10
      epidemic years, 1978 to 1988.
AB  - Respiratory syncytial virus strains isolated from infants and children
      hospitalized with acute respiratory tract disease in Huntington, W. Va., from
      July 1979 through June 1988 were categorized by subgroup by using two panels of
      monoclonal antibodies specific for subgroup A and subgroup B. Of 405 strains
      tested, 319 (78.8%) were subgroup A, 73 (18.0%) were subgroup B1, and 13 (3.2%)
      were subgroup B2. The subgroup B2 strains occurred as a single-season epidemic
      during the epidemiologic year July 1980 to June 1981, except for one strain
      isolated in the epidemiologic year 1978 to 1979. Subgroup B strains were
      associated with significantly fewer bronchiolitis illnesses than subgroup A
      strains. The severity of illnesses caused by subgroup B1 and B2 strains was the
      same.

PMID- 1993753
TI  - Improved immunoglobulin M serodiagnosis in Lyme borreliosis by using a mu-capture
      enzyme-linked immunosorbent assay with biotinylated Borrelia burgdorferi
      flagella.
AB  - A mu-capture enzyme-linked immunosorbent assay (ELISA) for detection of serum
      immunoglobulin M (IgM) antibodies to Borrelia burgdorferi by using biotinylated
      purified B. burgdorferi flagella was developed. The diagnostic performance of the
      mu-capture ELISA was compared with that of a conventional indirect ELISA. Sera
      from untreated patients with erythema migrans (n = 50), neuroborreliosis (n =
      100), and acrodermatitis chronica atrophicans (ACA; n = 48) were investigated.
      The cutoff of the ELISAs was adjusted to a diagnostic specificity of 98% on the
      basis of examination of 200 serum specimens from healthy controls. The mu-capture
      ELISA increased the diagnostic sensitivity in patients with erythema migrans from
      32 to 48% (P less than 0.01) and in patients with neuroborreliosis from 37 to 57%
      (P less than 0.001). Because of an increased signal/noise ratio, the mu-capture
      ELISA yielded a significantly better quantitative discrimination of individual
      positive measurements from the cutoff (P less than 0.001). The increased
      signal/noise ratio was most likely a consequence of the elimination of IgG
      competition for the test antigen. This may also explain why 12% of patients with
      ACA showed significantly increased specific IgM levels only by the mu-capture
      ELISA. Of patients with ACA, 27% had IgM rheumatoid factor. The mu-capture
      principle with a directly labeled antigen showed no interference with IgM
      rheumatoid factor, in contrast to the indirect ELISA. The high diagnostic
      performance and ease of this three-step mu-capture ELISA make it suitable for
      routine anti-B. burgdorferi IgM serodiagnosis.

PMID- 1993754
TI  - Validity of western immunoblot band patterns in the serodiagnosis of Lyme
      borreliosis.
AB  - Serodiagnosis of Lyme disease is hampered by low specificity of the standard
      assays currently used. The Western immunoblot has therefore been proposed as a
      potential confirmatory test. For the present report, the method was evaluated by
      testing sera from patients with clinically defined early- and late-stage
      borreliosis. In early-stage borreliosis, the 41,000-molecular-weight flagellin
      protein (41K) of Borrelia burgdorferi was the major antigen detected by
      antibodies in sera, but the specificity of the reaction pattern was dependent on
      the intensity of the band. The evaluation of different interpretation rules based
      on a semiquantitative record of band intensities showed the highest specificity
      (96%) and a corresponding sensitivity of 78% if there was at least one distinct
      (optical density range, 0.2 to 0.4) immunoglobulin G and immunoglobulin M
      reaction with the 41K band. Blots of B. burgdorferi proteins were also probed
      with sera from patients who were diagnosed by clinical criteria as having stage
      III Lyme borreliosis and with a control group of sera from asymptomatic persons
      with positive antibody titers against B. burgdorferi in the standard assays.
      Reaction patterns were recorded densitometrically. Statistical analysis and
      graphical marker analysis revealed significant discriminating capacities and
      relatively high specificities, respectively, for the 94K, 30K, and 21K bands,
      whereas the 41K and 60K bands were not discriminative between the symptomatic and
      asymptomatic groups and were specific only at high intensity values. Different
      multiple-band rules were evaluated, revealing a low specificity for positivity
      definitions of the type "four or five bands present" if the rules were not
      confined to known major bands.

PMID- 1993756
TI  - Comparison of different agars used in the formulation of buffered charcoal yeast
      extract medium.
AB  - The effect of agar type used for buffered charcoal yeast extract medium
      supplemented with 0.1% alpha-ketoglutarate was tested based on the growth and
      size of Legionella pneumophila. Oxoid Agar no. 1, Difco Bacto and Bitek agars,
      and BBL Granulated, Grade A, and Select agars were tested. For colony size the
      agars were ranked in the following order: Oxoid agar no. 1 much greater than
      Bacto greater than Bitek approximately Granulated approximately Grade A greater
      than Select. Colony yield per plate was similar for all agars except for Grade A,
      which gave significantly fewer colonies after 3 days, but not 4 days, of
      incubation. Agar type significantly influences L. pneumophila growth on buffered
      charcoal yeast extract medium supplemented with 0.1% alpha-ketoglutarate.

PMID- 1993755
TI  - Multivariate analyses of cellular fatty acids in Bacteroides, Prevotella,
      Porphyromonas, Wolinella, and Campylobacter spp.
AB  - The genera Bacteroides, Wolinella, and Campylobacter contain several similar
      species that require taxonomic revision. Fatty acid profiles of whole bacterial
      cells have proven useful for taxonomy. In this study, cellular fatty acids from
      Bacteroides, Prevotella, Porphyromonas, Wolinella, and Campylobacter spp. were
      identified and quantitated by gas chromatography and gas chromatography-mass
      spectrometry, and the data were subjected to principal component analyses.
      Bacteroides fragilis, the type species of the genus Bacteroides, was distinct
      from the other organisms. While Bacteroides gracilis, Wolinella succinogenes,
      Wolinella curva, Wolinella recta, and Campylobacter fetus subsp. venerealis were
      close to each other, Prevotella (Bacteroides) buccae, Prevotella oralis,
      Prevotella oris, Prevotella disiens, Prevotella veroralis, Prevotella
      heparinolyticus, Porphyromonas (Bacteroides) endodontalis, and Bacteroides
      ureolyticus could be distinguished. B. fragilis was characterized by the presence
      of C3OH-i-1-, Ca-15, and Ci-15 and the absence of C12:0 and unsaturated fatty
      acids. For comparison, B. gracilis, B. ureolyticus, W. succinogenes, W. curva, W.
      recta, and Campylobacter fetus subsp. venerealis contained C12:0, C16:1, C18:1,
      and C3-OH-14 acids but lacked branched hydroxy and branched nonhydroxy acids. B.
      gracilis and B. ureolyticus are not "true" bacteroides.

PMID- 1993757
TI  - Demonstration of a cell wall antigen cross-reacting with cryptococcal
      polysaccharide in experimental disseminated trichosporonosis.
AB  - Patients with disseminated infections caused by Trichosporon beigelii have a
      circulating antigen that cross-reacts with the polysaccharide capsule of
      Cryptococcus neoformans. We studied the localization of this antigen by
      immunoelectron microscopy in a rabbit model of experimental disseminated
      trichosporonosis. Deparaffinized lung sections were examined by using a murine
      monoclonal anti-cryptococcal polysaccharide antibody and colloidal gold particles
      coated with goat antibody to murine immunoglobulin G. Antigen that cross-reacted
      with the monoclonal antibody was observed in the T. beigelii cell wall and in a
      fibrillar matrix extending from the cell wall.

PMID- 1993758
TI  - Serological cross-reaction between Legionella pneumophila and Citrobacter
      freundii in indirect immunofluorescence and rapid microagglutination tests.
AB  - We describe the first case in which a diagnostic rise in titers of antibody to
      formalinized Legionella pneumophila serogroup 1 yolk sac antigen was shown to be
      caused by a cross-reaction between L. pneumophila and another organism,
      Citrobacter freundii.

PMID- 1993759
TI  - Detection and titration of measles virus antibody by hemagglutination inhibition
      and by dot immunobinding.
AB  - Measles continues to be a major disease of both human and nonhuman primates. The
      dot immunobinding assay, a modified enzyme immunoassay, permits the detection of
      measles virus antibody in the nonlaboratory setting with either serum or whole
      blood collected on filter paper.

PMID- 1993760
TI  - Differentiation between Trichophyton mentagrophytes and T. rubrum by sorbitol
      assimilation.
AB  - Trichophyton rubrum was easily differentiated from T. mentagrophytes by its
      ability to assimilate sorbitol with an API 20C AUX strip. One hundred percent of
      36 T. rubrum strains and none of 147 T. mentagrophytes strains assimilated
      sorbitol.

PMID- 1993761
TI  - Selective medium for Bacteroides gracilis.

PMID- 1993762
TI  - Molecular analysis of variant plasmid forms of a bivalent Salmonella typhi
      Shigella sonnei vaccine strain.
AB  - The Salmonella typhi-Shigella sonnei hybrid vaccine strain 5076-IC was
      constructed to express the S. sonnei form I antigen, which may play an important
      role in producing protective immunity. Three clonal variants which existed in
      preparations of the vaccine could be distinguished phenotypically by lactose
      utilization, S. sonnei form I antigen expression, and restriction enzyme analysis
      of large plasmid DNA. Since expression of the form I antigen was lost in two of
      the clonal variants, genetic instability of the 120-MDa vaccine plasmid appeared
      to be a potential problem. To examine the molecular basis of this genetic
      instability, we hybridized large plasmid DNA isolated from the clonal variants to
      a variety of DNA probes encoding virulence-associated antigens and to Escherichia
      coli lacZ DNA. Results indicated that DNA rearrangement accompanied by deletions
      of plasmid material occurred in the vaccine plasmid. In addition, the vaccine
      plasmid did not contain some S. sonnei genetic material encoding antigenic
      polypeptides necessary for virulence.

PMID- 1993763
TI  - Identification of toxigenic Clostridium difficile by the polymerase chain
      reaction.
AB  - Toxigenic strains of Clostridium difficile are causative agents of
      pseudomembranous colitis and antimicrobial agent-associated diarrhea and colitis.
      The toxigenicity is routinely assayed by using highly sensitive cell cultures. We
      used a simple and rapid polymerase chain reaction (PCR) assay to differentiate
      toxigenic and nontoxigenic strains of C. difficile. Two sets of oligonucleotide
      primer pairs derived from nonrepeating sequences of the toxin A gene were used to
      amplify 546- and 252-bp DNA fragments. A primer pair derived from repeating
      sequences of the toxin A gene was used to amplify a 1,266-bp DNA product.
      Amplified products were visualized by polyacrylamide gel electrophoresis followed
      by ethidium bromide staining. All 35 cytotoxic strains of C. difficile tested
      generated the expected amplified DNA. In contrast, none of the 26 noncytotoxic
      strains tested gave positive results. Although the toxins of C. difficile have
      been demonstrated to cross-react serologically with the toxins of Clostridium
      sordellii, we did not detect any amplified DNA in two cytotoxic strains or seven
      noncytotoxic strains of C. sordellii. PCR was negative in all 30 strains of 20
      other Clostridium species. Southern hybridization of HindIII-digested genomic DNA
      by use of subgenomic probes showed a single hybridization band in toxigenic
      strains but not in nontoxigenic strains. PCR appears to be a sensitive and
      specific assay for the rapid identification of toxigenic C. difficile.
      Nontoxigenic C. difficile appeared to lack the C. difficile toxin A gene.

PMID- 1993764
TI  - Evaluation of API Coryne in comparison with conventional methods for identifying
      coryneform bacteria.
AB  - A study was performed to evaluate a new manual miniaturized system, API Coryne
      (API-bioMerieux, Inc., La Balme les Grottes, France), in which conventional
      biochemical methods were used to identify 240 isolates of coryneform and related
      bacteria. A total of 40% of the isolates were excluded from the study because
      they could not be identified by conventional methods. Identifications of the 240
      isolates obtained with API Coryne showed a 97.6% concordance with conventional
      methods (79% after 24 h of incubation, 21% after 48 h of incubation): 158 (65.8%)
      isolates were identified with no further testing, and extra testing was required
      for 76 (31.8%) isolates. In three (1.2%) cases, the organisms did not correspond
      to any key in the code book and could not be identified by the computer service
      of the manufacturer. Only three (1.2%) strains were misidentified. The system was
      shown to be reliable and rapid when compared with standard identification
      methods.

PMID- 1993765
TI  - Diagnostic value of the polymerase chain reaction for Chlamydia detection as
      determined in a follow-up study.
AB  - The diagnostic value of the polymerase chain reaction (PCR) for detection of
      Chlamydia trachomatis in comparison with that of the culture technique was
      established in a follow-up study of 32 patients (81 samples) who were treated for
      a C. trachomatis infection. The PCR was performed with two different sets of
      primers, a genus-specific primer set directed against the rRNA genes and a C.
      trachomatis-specific set directed against the common endogenous plasmid. After
      treatment with doxycycline, all patients became culture negative after 1 week.
      Results for the detection of C. trachomatis by the PCR were in complete agreement
      with the results by the culture method of detection, except for one culture
      negative sample, which was found to be positive by the PCR. The results indicated
      that 1 week after treatment, no residual chlamydial DNA was found in the samples.
      Therefore, the PCR can be used for monitoring infections by chlamydiae.

PMID- 1993766
TI  - Polymerase chain reaction for detection of Mycoplasma genitalium in clinical
      samples.
AB  - We have used the polymerase chain reaction to detect Mycoplasma genitalium in
      artificially seeded human throat swab samples as well as in clinical material. On
      the basis of the published nucleotide sequence of the M. genitalium 140-kDa
      adhesin gene, primers were chosen to produce an amplified fragment of 281 bp.
      Five different previously isolated strains, including the type strain of M.
      genitalium, could all be detected by the polymerase chain reaction, and DNAs from
      other mycoplasmal and bacterial species yielded negative results. The detection
      limits were estimated to be approximately 50 organisms by inspection of ethidium
      bromide-stained agarose gels and 4 organisms when a biotinylated oligonucleotide
      probe was used in filter hybridization. The amplified DNA fragments were
      subjected to restriction enzyme analysis. DNAs from the five different isolates
      all possessed EcoRI, SspI, AluI, Sau3AI, and DdeI restriction sites, as predicted
      from the published sequence. A total of 150 urogenital swabs collected from 100
      patients for culturing of Chlamydia trachomatis were tested for the presence of
      M. genitalium DNA. Ten samples from eight patients were found positive. The
      amplified DNA fragments from all of our clinical samples possessed the AluI,
      Sau3AI, and DdeI restriction sites, but three samples from two patients did not
      contain the SspI site and none of the samples contained the EcoRI site.

PMID- 1993767
TI  - Evaluation of techniques for isolation, subcultivation, and preservation of
      Helicobacter pylori.
AB  - With sheep blood agar (SBA), Belo Horizonte medium, and Brussels campylobacter
      charcoal agar, 104 strains of Helicobacter pylori were detected in 309 gastric
      biopsies. Each medium revealed only 69 to 71% of the strains. Ten strains grew
      solely on SBA, and four strains each grew on Belo Horizonte medium and Brussels
      campylobacter charcoal agar. Subculturing of 50 fresh H. pylori isolates on SBA
      revealed a progressive reduction in growth with increasing passage. Thirty
      strains stopped growing between passages two and seven. Four strains survived
      more than 20 passages. The preservation of fresh H. pylori isolates at -193 and 
      70 degrees C and by lyophilization was compared by use of 10% porcine mucin
      solution, fetal calf serum, and a commercial cryopreservative fluid. Of 30
      strains, 77 to 90% could be recultivated on SBA after preservation at -70 degrees
      C in all three storage media. The data indicate that for the primary isolation of
      H. pylori, not only one selective medium but several selective media with
      different antibiotic supplements plus at least one nonselective medium should be
      used to yield the highest culture rates. Frequent subculturing of H. pylori on
      SBA selects strains which may not be representative of clinical isolates. Storage
      of fresh H. pylori isolates at -70 degrees C in 10% mucin solution is a simple
      and effective preservation procedure.

PMID- 1993768
TI  - Biochemical and serological characterization of Campylobacter cryaerophila.
AB  - Sixty-two isolates of Campylobacter cryaerophila were recovered from aborted
      porcine and bovine fetuses, from porcine, bovine, and equine feces, and from
      different tissues of a dead piglet. Phenotypic characterization was carried out
      on all isolates, and the results were compared with those obtained with the
      reference strains of C. cryaerophila, C. jejuni, C. coli, C. laridis, and C.
      hyointestinalis. The ability of C. cryaerophila strains to grow under aerobic
      conditions at 16 degrees C was found to be most useful in differentiating them
      from strains of other Campylobacter species. Studies were undertaken to develop a
      serotyping system for C. cryaerophila on the basis of the Lior serotyping system
      for C. jejuni and C. coli by use of a tube agglutination test with formalinized
      whole-cell (FWC) and boiled whole-cell (BWC) antigens. Antisera against 18
      strains of C. cryaerophila were produced in rabbits. Thirty-five percent of C.
      cryaerophila strains were typed with the FWC suspension as an antigen, and 61%
      were typed with the BWC suspension as an antigen. None of the C. cryaerophila
      strains tested autoagglutinated in saline. BWC antigens of C. jejuni, C. coli,
      and C. laridis cross-reacted with C. cryaerophila, whereas FWC antigens did not
      cross-react. Neither FWC nor BWC antigens of C. hyointestinalis reacted with C.
      cryaerophila antisera.

PMID- 1993769
TI  - Evaluation of the Staph-Zym system with staphylococci isolated from bovine
      intramammary infections.
AB  - A total of 148 staphylococci isolated from bovine intramammary infections were
      used to evaluate the Staph-Zym system (ROSCO, Taastrup, Denmark). The overall
      accuracy of the system was 91.9%. The system correctly identified all strains of
      Staphylococcus aureus, Staphylococcus simulans, and Staphylococcus xylosus and
      95% of Staphylococcus intermedius strains. Of 33 Staphylococcus hyicus strains,
      31 (93.9%) were classified correctly by the Staph-Zym system, as well as 8 (80%)
      of 10 Staphylococcus chromogenes strains. All 11 Staphylococcus epidermidis
      strains and the 1 Staphylococcus haemolyticus strain included in the study were
      identified, but the Staph-Zym system had difficulty distinguishing strains of
      Staphylococcus warneri and Staphylococcus hominis from other species in the S.
      epidermidis group. The Staph-Zym system correctly identified all six S. xylosus
      strains and two of three Staphyloccus sciuri strains. The Staph-Zym system was
      considered an acceptable alternative to conventional methods for identification
      of bovine mammary gland isolates.

PMID- 1993770
TI  - Sensitive detection of Treponema pallidum by using the polymerase chain reaction.
AB  - We have developed a sensitive assay for Treponema pallidum subsp. pallidum (T.
      pallidum), the agent of veneral syphilis, based upon the polymerase chain
      reaction (PCR). A 658-bp portion of the gene encoding the 47-kDa membrane
      immunogen was amplified, and the PCR products were probed by DNA-DNA
      hybridization with a 496-bp fragment internal to the amplitifed DNA. The assay
      detected approximately 0.01 pg of purified T. pallidum DNA, and positive results
      were obtained routinely from suspensions of treponemes calculated to contain 10
      or more organism and from some suspensions calculated to contain a single
      organism. Specific PCR products were obtained for the closely related agent of
      yaws, Treponema pallidum subsp. pertenue, but not with human DNA or DNAs from
      other spirochetes (including Borrelia burgdoferi), skin microorganisms, sexually
      transmitted disease pathogens, and central nervous system pathogens. T. pallidum
      DNA was detected in serum, cerebrospinal fluids, and amniotic fluids from
      syphilis patients but not in in nonsyphilitic controls. T. pallidum DNA was also
      amplified from paraffin-embedded tissue. The diagnosis of syphillis by using PCR
      may become a significant addition to the diagnostic armamentarium and a valuable
      technique for the investigation of syphilis pathogenesis.

PMID- 1993771
TI  - Etiology of childhood diarrhea in Beijing, China.
AB  - To determine the role of recently recognized enteropathogens in childhood
      diarrhea in China, 221 children with diarrhea and 108 controls seen at the
      Beijing Children's Hospital were studied during April and May 1989. Stools were
      examined for ova, parasites, and rotavirus, cultured for bacterial pathogens, and
      probed for enterotoxigenic Escherichia coli (ETEC), enteroinvasive E. coli
      (EIEC), enterohemorrhagic E. coli (EHEC), and enteropathogenic adherence factor
      positive (EAF+) E. coli. Pathogens were identified in 56.5% of children with
      diarrhea and 43.5% of controls (P = 0.04). Detection of enteropathogens was
      significantly greater in patients examined within 1 week of symptom onset (65%)
      than in patients examined later (39%; P = 0.01). ETEC was the most frequently
      detected pathogen in children with diarrhea, accounting for 20% of the cases.
      Other agents identified in patients included the following: salmonellae, 12%;
      rotavirus, 7%; EIEC, 7%; EHEC, 7%; members of the Aeromonas hydrophila group, 6%;
      EAF+ E. coli, 5%; Ascaris lumbricoides, 3%; shigellae, 3%; campylobacters, 2%;
      and Vibrio spp., 0.5%. The isolation rates of salmonellae (P = 0.02), EAF+ E.
      coli (P = 0.04), and mixed pathogens (P = 0.05) were significantly greater for
      diarrhea patients than for controls. Resistance to multiple antimicrobial agents
      occurred in 39% of the Salmonella isolates, 22% of the Aeromonas isolates, and
      17% of the Shigella isolates. Multiresistant salmonellae (P = 0.05) and shigellae
      were recovered from diarrheal stools only. Ciprofloxacin, cefotaxime, and
      imipenem were the only agents tested to which all bacterial isolates were
      susceptible in vitro. These results suggest that both traditional and newly
      recognized agents are important causes of childhood diarrhea in Beijing and that
      therapy may be complicated by indigenous antimicrobial resistance.

PMID- 1993772
TI  - Comparison of the lysis-centrifugation and agitated biphasic blood culture
      systems for detection of fungemia.
AB  - Although the detection of fungemia has been improved by the use of vented or
      biphasic blood culture bottles, the best recovery and earliest detection have
      been reported in the Isolator lysis-centrifugation system. It was recently
      demonstrated that improved detection of both bacteria and fungi was accomplished
      by mechanically agitating blood culture bottles for the first 24 h of incubation.
      In this study the detection of fungemia by use of the Isolator system was
      compared with that of an agitated biphasic system. A total of 182 fungi were
      isolated from blood specimens inoculated into both culture systems. No difference
      in the overall recovery of fungi or individual species of yeasts was observed
      between the two systems. However, all seven isolates of Histoplasma capsulatum
      were recovered in the Isolator system only. The time required to detect fungemia
      with each of the two systems was also compared. No statistically significant
      difference was observed. From the data collected during this 18-month study, it
      can be concluded that the overall recovery and time of detection of yeasts are
      equivalent in the lysis-centrifugation system and the agitated biphasic blood
      culture system. The lysis-centrifugation system is still superior for the
      detection of filamentous fungi such as H. capsulatum.

PMID- 1993773
TI  - Production and characterization of a monoclonal antibody specific for
      enterohemorrhagic Escherichia coli of serotypes O157:H7 and O26:H11.
AB  - A monoclonal antibody (MAb 4E8C12) specific for Escherichia coli O157:H7 and
      O26:H11 was produced by immunizing BALB/c mice with a rough strain of E. coli
      O157:H7. The antibody reacted strongly by a direct enzyme-linked immunosorbent
      assay with each of 36 strains of E. coli O157:H7. No cross-reactivity was
      observed with strains of Salmonella spp., Yersinia enterocolitica, Shigella
      dysenteriae, Proteus spp., Escherichia hermanii, Klebsiella pneumoniae,
      Campylobacter jejuni, Serratia marcescens, Citrobacter spp., Enterobacter
      cloacae, Hafnia alvei, Aeromonas hydrophila, and all except five strains of E.
      coli other than serotype O157:H7 (including strains of serotype O157 but not H7).
      The E. coli strains (all of serotype O26:H11) that reacted with the antibody were
      enterohemorrhagic E. coli (EHEC) that were isolated from patients with hemolytic
      uremic syndrome or hemorrhagic colitis and produced verotoxin similar to that of
      E. coli O157:H7. MAb 4E8C12 belongs to the subclass immunoglobulin G2a and has a
      kappa light chain. Tricine-sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis of outer membrane proteins of E. coli of different serotypes
      followed by Western immunoblot analysis revealed that MAb 4E8C12 reacted
      specifically with two proteins of EHEC strains of serotypes O157:H7 and O26:H11
      with apparent molecular weights of 5,000 to 6,000. These proteins appeared to be
      markers specific for EHEC strains of serotypes O157:H7 and O26:H11. This MAb,
      because of its specificity, may be a useful reagent of an immunoassay for the
      rapid detection of these types of EHEC isolates in clinical and food specimens.

PMID- 1993774
TI  - Guidelines and indications for coronary artery bypass graft surgery. A report of
      the American College of Cardiology/American Heart Association Task Force on
      Assessment of Diagnostic and Therapeutic Cardiovascular Procedures (Subcommittee
      on Coronary Artery Bypass Graft Surgery).

PMID- 1993775
TI  - Digoxin Immune Fab therapy in the management of digitalis intoxication: safety
      and efficacy results of an observational surveillance study.
AB  - An observational surveillance study was conducted to monitor the safety and
      effectiveness of treatment with Digoxin Immune Fab (Ovine) (Digibind) in patients
      with digitalis intoxication. Before April 1986, a relatively limited number of
      patients received treatment with digoxin-specific Fab fragments through a
      multicenter clinical trial. Beginning with commercial availability in July 1986,
      this study sought additional, voluntarily reported clinical data pertaining to
      treatment through a 3 week follow-up. The study included 717 adults who received
      Digoxin Immune Fab (Ovine). Most patients were greater than or equal to 70 years
      old and developed toxicity during maintenance dosing with digoxin. Fifty percent
      of patients were reported to have a complete response to treatment, 24% a partial
      response and 12% no response. The response for 14% of patients was not reported
      or reported as uncertain. Six patients (0.8%, 95% confidence interval 0.3% to
      1.8%) had an allergic reaction to digoxin-specific antibody fragments. Three of
      the six had a history of allergy to antibiotic drugs. Twenty patients (2.8%, 95%
      confidence interval 1.7% to 4.3%) developed recrudescent toxicity. Risk of
      recrudescent toxicity increased sixfold when less than 50% of the estimated dose
      of antibody was administered. A total of 215 patients experienced posttreatment
      adverse events. The events for 163 patients (76%) were judged to result from
      manifestations of underlying disease and thus considered unrelated to Fab
      treatment. Digoxin-specific antibody fragments were generally well tolerated and
      clinically effective in patients judged by treating physicians to have
      potentially life-threatening digitalis intoxication.

PMID- 1993776
TI  - Multicenter registry of angioplasty therapy of cardiogenic shock: initial and
      long-term survival.
AB  - This retrospective multicenter study reviews the role of acute percutaneous
      transluminal coronary angioplasty in the treatment of cardiogenic shock
      complicating acute myocardial infarction to determine whether early reperfusion
      affects in-hospital and long-term survival. From 1982 to 1985, 69 patients were
      treated with emergency angioplasty to attempt reperfusion of the infarct-related
      artery. Balloon angioplasty was unsuccessful in 20 patients (group 1) and
      successful in 49 patients (group 2). Initial clinical and angiographic findings
      in the groups with unsuccessful and successful angioplasty were similar with
      respect to age (60.5 +/- 2.3 versus 57 +/- 1.8 years), infarct location (65%
      versus 65% anterior) and gender (65% versus 67% male). Hemodynamic variables in
      the two groups, including systolic blood pressure (68 +/- 4.3 versus 73 +/- 1.6
      mm Hg), left ventricular end-diastolic pressure (24.4 +/- 2.4 versus 27 +/- 1.0
      mm Hg) and initial ejection fraction (28.5 +/- 4% versus 32 +/- 2%), were also
      similar. Twenty-nine patients received thrombolytic therapy with streptokinase;
      the overall rate of reperfusion was 34%. Group 1 patients had a short-term
      survival rate of 20%, compared with 69% in group 2 patients (p less than 0.0005).
      Thirty-eight patients survived the hospital period and were followed up for 24 to
      54 months (mean 32.5 +/- 2.4). Five patients (all in group 2) died during follow
      up. The long-term incidence rate of congestive heart failure was 19%, arrhythmia
      21%, need for repeat angioplasty 17% and coronary artery bypass grafting 26%.
      Twenty-four month survival was significantly better in group 2 patients (54%)
      versus group 1 patients (11%, p = 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1993777
TI  - Factors determining improvement in left ventricular function after reperfusion
      therapy for acute myocardial infarction: primacy of baseline ejection fraction.
AB  - Improvement in left ventricular ejection fraction is a measure of salvage of
      ischemic myocardium after reperfusion therapy for acute myocardial infarction.
      The degree of improvement in left ventricular ejection fraction may be influenced
      by many factors. Therefore, 137 patients in whom paired radionuclide angiograms
      were obtained within 24 h of acute infarction and before hospital discharge were
      retrospectively evaluated to determine which factors most affect improvement in
      ejection fraction. Only baseline ejection fraction correlated significantly with
      improvement in ejection fraction by both univariate analysis (ejection fraction
      as a continuous variable; p less than 0.001; ejection fraction as a categorical
      variable, less than or equal to 45% versus greater than 45%, p less than 0.0001)
      and multivariate analysis (p less than 0.0001). Reperfusion status (patent versus
      occluded infarct artery) and extent of coronary artery disease (one, two or three
      vessel) were significant factors by multivariate but not by univariate analysis.
      Location of infarction, treatment modality and time to treatment did not
      correlate with change in ejection fraction by either statistical technique. Thus,
      of those factors tested, baseline left ventricular ejection fraction is the most
      potent predictor of improvement in ventricular function after acute infarction.
      Knowledge of baseline ejection fraction may be helpful in deciding whether to
      treat some patients with equivocal indications or contraindications for
      reperfusion therapy. Clinical trials of reperfusion strategies should stratify
      patients on the basis of baseline ejection fraction if ejection fraction is to be
      used as an end point for myocardial salvage.

PMID- 1993778
TI  - Incidence and clinical significance of transient creatine kinase elevations and
      the diagnosis of non-Q wave myocardial infarction associated with coronary
      angioplasty.
AB  - To assess the incidence and clinical significance of elevated total plasma
      creatine kinase (CK) and MB isoenzyme fraction after apparently successful
      coronary angioplasty, a prospective study of 272 consecutive elective procedures
      was undertaken. Total CK (normal less than 100 IU/liter) and CK MB isoenzyme
      (normal less than 4%) were measured immediately after successful completion of
      the procedure and every 6 h for 24 h. All nonelective procedures and results not
      fulfilling all American Heart Association/American College of Cardiology Task
      Force guideline criteria for a successful result were excluded from analysis. Of
      the 272 elective procedures, 249 (92%) were successfully; abnormally elevated CK
      or CK MB serum levels, or both, were found in 38 (15%) of the successful
      outcomes. Three patterns of abnormal enzymes were identified: 15 patients with CK
      greater than or equal to 200 IU/liter and CK MB greater than or equal to 5%
      (group 1), 4 patients with CK greater than or equal to 200 IU/litter and CK MB
      less than or equal to 4% (group 2) and 19 patients with CK less than 200 IU/liter
      and CK MB greater than or equal to 5% (group 3). The three groups were
      distinguishable by the nature of the complications causing the enzyme release (in
      particular, the etiology and clinical manifestations). There were significantly
      more clinically apparent events in group 1 than in the other groups (13 of 15
      versus 11 of 23, p less than 0.01) and more events associated with persistent
      electrocardiographic changes (p = 0.05) and chest pain (p less than 0.05).
      However, no clinically important sequelae were recognizable in any group at
      hospital discharge. Thus, abnormal cardiac serum enzyme release after apparently
      successful coronary angioplasty is 1) relatively common; 2) has many possible
      causes, including both minor complications and early reversibility of impending
      major complications; and 3) results in no permanent clinical sequelae.

PMID- 1993779
TI  - Reactivity of eccentric and concentric coronary stenoses in patients with chronic
      stable angina.
AB  - Dynamic coronary stenoses may be the cause of a variable angina threshold and
      rest angina in patients with chronic stable angina. It has been suggested that
      eccentric but not concentric coronary artery stenoses have the potential for
      dynamic changes of caliber in response to vasoactive stimuli. The vasomotor
      response of eccentric (asymmetric narrowing) and concentric (symmetric narrowing)
      coronary stenoses to ergonovine (20 micrograms intracoronary or 300 micrograms
      intravenous) and isosorbide dinitrate (1 mg intracoronary) was studied in 51
      patients with chronic stable angina. Diameter of reference segments
      (angiographically normal segments proximal to the stenoses) and that of eccentric
      (n = 30) and concentric (n = 35) coronary stenoses that ranged from 50% to 90%
      luminal diameter reduction were measured by computerized quantitative angiography
      before and after ergonovine and isosorbide dinitrate. Ergonovine reduced stenosis
      diameter (by greater than or equal to 10%) in 80% of eccentric stenoses and 42%
      of concentric stenoses (p less than 0.05). Mean (+/- SEM) diameter reduction with
      ergonovine was 19 +/- 3% and 9.5 +/- 2% for eccentric and concentric stenoses,
      respectively (p less than 0.05). Isosorbide dinitrate increased coronary diameter
      (by greater than or equal to 10%) in 70% of eccentric and 43% of concentric
      stenoses (p less than 0.05). Mean diameter of eccentric stenoses increased from
      1.15 +/- 0.05 to 1.35 +/- 0.06 mm after nitrate (18.6 +/- 2.5%), whereas diameter
      of concentric stenoses increased from 1.05 +/- 0.05 to 1.14 +/- 0.05 mm (10 +/-
      2.5%) (p less than 0.05). Average dilation of reference segments with
      administration of isosorbide dinitrate and constriction with ergonovine were not
      significantly different in patients with concentric and eccentric
      stenoses.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1993780
TI  - Long-term follow-up of medical versus surgical therapy for hypertrophic
      cardiomyopathy: a retrospective study.
AB  - In a retrospective analysis 139 patients with hypertrophic cardiomyopathy were
      followed up for 8.9 years (range 1 to 28 years). Patients were divided into two
      groups: Group 1 consisted of 60 patients with medical therapy and Group 2 of 79
      patients with surgical therapy (septal myectomy). Groups 1 and 2 were subdivided
      according to the medical treatment. Group 1a received propranolol, 160 mg/day (n
      = 20); Group 1b verapamil, 360 mg/day (n = 18); and Group 1c, no therapy (n =
      22). Group 2a received verapamil, 120 to 360 mg/day, after septal myectomy (n =
      17) and Group 2b had no medical therapy after surgery (n = 62). In Group 1, 19
      patients died (annual mortality rate 3.6%) and in Group 2, 17 patients died
      (mortality rate 2.4%, p = NS). Of the patients who died, approximately one half
      to two thirds in both Groups 1 and 2 died suddenly and the other one half to one
      third died because of congestive heart failure. The 10 year cumulative survival
      rate was 67% in Group 1, significantly smaller than that in Group 2 (84%, p less
      than 0.05). In the subgroups, the 10 year survival rate was 67% in Group 1a, 80%
      in 1b (p less than 0.05 versus 1a) and 65% in 1c (p less than 0.05 versus 1b).
      The 10 year survival rate was 100% in Group 2a (p less than 0.05 versus 1a, 1b,
      1c) and 78% in Group 2b (p less than 0.05 versus 2a). It is concluded that
      cumulative survival rate is significantly better in surgically than in medically
      treated patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1993781
TI  - Surgical versus medical therapy of hypertrophic cardiomyopathy: is the
      perspective changing?

PMID- 1993782
TI  - Obstruction of mechanical heart valve prostheses: clinical aspects and surgical
      management.
AB  - One hundred patients (32 male) aged 5 months to 82 years (median 32 years)
      underwent 106 surgical procedures for 112 mechanical prosthetic valves obstructed
      by a thrombus (n = 61) or pannus (n = 7), or both (n = 44), between January 1,
      1980 and December 31, 1989. The position of the obstructed prosthesis was aortic
      in 51 patients (48%), mitral in 49 (46%) and both aortic and mitral in 6 (6%).
      The types of obstructed prosthetic valves were Bjork-Shiley (n = 51), St. Jude (n
      = 41) and Medtronic-Hall (n = 20). The time interval between valve replacement
      and obstruction ranged from 6 weeks to 13 years (median 4 years). Of 63% of
      patients in whom coagulation variables were available at the time of obstruction,
      70% were receiving inadequate anticoagulant therapy. In 63% of the procedures the
      patient was in New York Heart Association functional class IV. Two patients
      underwent preoperative thrombolysis with incomplete results. Operative procedures
      included valve replacement (n = 81), valve declotting and excision of pannus (n =
      23) and aortic valve replacement and mitral valve declotting (n = 2). The early
      mortality rate was 12.3% (13 patients), and there was no difference between
      surgery for mitral prostheses (12.2%) versus aortic prostheses (13.7%). The
      perioperative mortality rate was 17.5% (11 of 63 patients) in patients in
      functional class IV and 4.7% (2 of 43 patients) in those in functional classes I
      to III (p less than 0.05). For valve replacement, the mortality rate was 12% (10
      of 81 patients) and for declotting of the prosthesis 13% (3 of 23
      patients).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1993783
TI  - Myocardial magnesium: relation to laboratory and clinical variables in patients
      undergoing cardiac surgery.
AB  - Magnesium concentration was measured in the right atrial appendage of 100
      patients undergoing cardiac surgery and associations with serum and mononuclear
      blood cell magnesium, other laboratory values and patient clinical variables were
      studied. In addition, magnesium was measured in the right atrial appendage and
      left ventricular free wall in 23 autopsy subjects to determine whether there was
      a proportional relation between right atrial appendage and left ventricular free
      wall magnesium. The mean left ventricular free wall/right atrial appendage
      magnesium ratio was 2.13 +/- 0.39 (r = 0.67, p = 0.0009). In the group with
      cardiac surgery, the right atrial appendage magnesium concentration correlated
      inversely with age (r = -0.54, p = 0.001). The mean right atrial appendage
      magnesium concentration (micrograms/g wet weight tissue) was lower in patients
      with postoperative cardiac arrhythmia than in those without arrhythmia (103 +/-
      13 versus 111 +/- 10, p = 0.009) and in diabetic than in nondiabetic patients
      (103 +/- 13 versus 109 +/- 12, p = 0.02). The right atrial appendage magnesium
      concentration also tended to be lower in patients receiving potassium/magnesium
      losing diuretics, although this difference did not achieve statistical
      significance (105 +/- 14 versus 109 +/- 11, p = 0.16). Right atrial appendage
      magnesium concentration correlated positively with serum creatinine concentration
      (r = 0.31, p = 0.002) and negatively with serum calcium concentration (r = -0.29,
      p = 0.013). Serum magnesium did not correlate with right atrial appendage or
      mononuclear blood cell magnesium concentration or clinical variables. There was a
      statistically significant correlation between mononuclear blood cell and right
      atrial appendage magnesium concentrations in some subgroups of patients.

PMID- 1993784
TI  - Prediction of the frequency and duration of ambulatory myocardial ischemia in
      patients with stable coronary artery disease by determination of the ischemic
      threshold from exercise testing: importance of the exercise protocol.
AB  - The relation between ambulatory myocardial ischemia and the results of exercise
      testing in patients with ischemic heart disease remains undefined, because of the
      dissimilar results of previous reports. To further investigate this issue and, in
      particular, to ascertain the importance of the exercise protocol in determining
      that relation, 70 patients with stable coronary artery disease underwent 48 h
      ambulatory electrocardiographic (ECG) monitoring and treadmill exercise tests
      after withdrawal of medications. Patients exercised using two different protocols
      with slow (National Institutes of Health [NIH] combined protocol) and brisk
      (Bruce protocol) work load increments. Exercise duration was longer with the NIH
      combined protocol (14.1 +/- 5 versus 6.8 +/- 2 min; p less than 0.0001), but the
      maximal work load and peak heart rate achieved were greater with the Bruce
      protocol (9.8 +/- 2 versus 6.5 +/- 2 METs, and 142 +/- 19 versus 133 +/- 22
      beats/min, respectively; p less than 0.0001). A close inverse correlation between
      exercise testing and the results of ambulatory ECG monitoring was observed using
      the NIH combined protocol; the strongest correlation was observed between time of
      exercise at 1 mm of ST segment depression and number of ischemic episodes (r = 
      0.86; p less than 0.0001). With the Bruce protocol a significantly weaker inverse
      correlation was found (r = -0.35). The mean heart rate at the onset of ST segment
      depression was similar during monitoring and during exercise testing with the NIH
      combined protocol (97.2 +/- 13 versus 101.0 +/- 17 beats/min, respectively) but
      it was significantly higher (110.4 +/- 13) when using the Bruce protocol (p less
      than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1993785
TI  - Differences in electrocardiographic demonstration of myocardial ischemia.

PMID- 1993787
TI  - Silent ischemia after coronary angioplasty: evaluation of restenosis and extent
      of ischemia in asymptomatic patients by tomographic thallium-201 exercise imaging
      and comparison with symptomatic patients.
AB  - One hundred sixteen patients were evaluated to determine the ability of single
      photon emission computed tomographic (SPECT) thallium-201 exercise and
      redistribution imaging to detect silent ischemia secondary to restenosis in
      asymptomatic patients after single and multiple vessel percutaneous transluminal
      coronary angioplasty and the findings were compared with SPECT imaging detection
      of restenosis in symptomatic patients. The value of exercise electrocardiography
      (ECG) and the amount of ischemic myocardium in symptomatic and asymptomatic
      patients were determined. Forty-one patients were asymptomatic after angioplasty;
      77% of these had chest pain before angioplasty. Seventy-five patients had chest
      pain after angioplasty; 99% of these had chest pain before angioplasty.
      Restenosis occurred in 61% of asymptomatic and 59% of symptomatic patients and in
      46% of the vessels in both asymptomatic and symptomatic patients. Sensitivity,
      specificity and accuracy for detection of restenosis by SPECT in individual
      patients were 96%, 75% and 88% versus 91%, 77% and 85%, respectively, in the
      asymptomatic versus symptomatic groups (p = NS). Sensitivity, specificity and
      accuracy for restenosis detection in individual vessels were 90%, 89% and 89%
      versus 84%, 77% and 84%, respectively, in the asymptomatic and symptomatic groups
      (p = NS), with similar results for the three major arteries. Sensitivity and
      accuracy of exercise ECG were significantly less than those of SPECT imaging for
      the patients with silent (40% and 44%) and symptomatic (59% and 64%) ischemia (p
      less than 0.001). Restenosis of vessels in the patients with silent and
      symptomatic ischemia was associated with an equal amount and degree of severity
      of ischemic myocardium in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1993786
TI  - Stress echocardiography and the human factor: the importance of being expert.
AB  - The aim of this study was to evaluate how the diagnostic accuracy of a stress
      echocardiographic procedure, such as a dipyridamole echocardiography test,
      depends on the specific experience of the physician interpreting the test.
      Recordings of 50 consecutive dipyridamole echocardiographic tests were selected
      for the first part of the study. They were analyzed by 20 experienced
      echocardiographers with different backgrounds in stress echocardiography: 10
      beginners (less than 20 stress studies interpreted with trained staff) and 10
      experienced observers (greater than or equal to 100 stress studies performed).
      Diagnostic accuracy (true positive + true negative/total number of tests) versus
      the angiographic reference standard (greater than 70% coronary stenosis of at
      least one major coronary artery) was 62 +/- 6% for beginners and 85 +/- 3% for
      experienced observers (p less than 0.0001). In the second part of the study, 10
      observers (5 beginners and 5 experienced observers) evaluated 2 different sets of
      50 dipyridamole echocardiographic test studies before and after the training of
      the beginners. Before training, the accuracy of beginners was lower than that of
      experienced observers (61 +/- 7% versus 85 +/- 3%; p less than 0.001). After
      training, the accuracy gap was closed (83 +/- 3% versus 86 +/- 2%; p = NS).
      Therefore, interpretation of stress echocardiographic tests by an
      echocardiographer without specific training severely underestimates the
      diagnostic potential of this technique. One hundred stress echocardiographic
      studies are more than adequate to build the individual learning curve and reach
      the plateau of diagnostic accuracy that the test can yield.

PMID- 1993788
TI  - Concealed entrainment as a guide for catheter ablation of ventricular tachycardia
      in patients with prior myocardial infarction.
AB  - Fifteen consecutive patients with drug-refractory, recurrent, sustained,
      monomorphic ventricular tachycardia and a history of remote myocardial infarction
      underwent catheter ablation of ventricular tachycardia. Shocks of 100 to 300 J
      were delivered to sites at which pacing during ventricular tachycardia resulted
      in concealed entrainment, in which the ventricular tachycardia accelerated to the
      pacing rate, there was a long stimulus to QRS interval and there was no change in
      the configuration of the QRS complex during pacing at several rates compared with
      the configuration during ventricular tachycardia, thus identifying a zone of slow
      conduction in the reentrant circuit. Concealed entrainment was demonstrated in
      nine (60%) of 15 patients, and the stimulus to QRS intervals were 90 to 400 ms.
      At sites of concealed entrainment, the endocardial activation time relative to
      the QRS complex during ventricular tachycardia ranged from -125 to +50 ms, the
      timing of the local electrogram relative to the QRS complex was the same during
      entrainment as during ventricular tachycardia and the pace map during sinus
      rhythm was discordant with that of the ventricular tachycardia in seven patients.
      In the six patients in whom a site of concealed entrainment could not be
      identified, the target site for ablation was selected on the basis of
      identification of an isolated mid-diastolic potential, activation mapping and
      pace mapping. The mean (+/- SD) cumulative number of joules delivered to the
      target site was 306 +/- 140. A successful long-term clinical outcome was achieved
      in 9 of the 15 patients (mean follow-up 20 +/- 7 months). The clinical success
      rate was the same whether the target site was selected on the basis of concealed
      entrainment (five of nine, 56%) or on the basis of the other mapping techniques
      (four of six, 67%). In conclusion, the responses to pacing suggest that sites at
      which there is concealed entrainment may be located within a zone of slow
      conduction in the ventricular tachycardia reentry circuit, although not
      necessarily in an area critical for the maintenance of reentry. The long-term
      clinical efficacy of catheter ablation targeted to sites of concealed entrainment
      is about 60%, similar to the results achieved when conventional mapping
      techniques are used.

PMID- 1993789
TI  - Effects of standing on the induction of paroxysmal supraventricular tachycardia.
AB  - To evaluate the effects of standing on induction of paroxysmal supraventricular
      tachycardia, electrophysiologic studies were performed in both the supine and
      standing positions in 22 patients with atrioventricular (AV) reciprocating
      tachycardia and in 11 with AV node reentrant tachycardia. AV reciprocating
      tachycardia was induced in 9 of the 22 patients with AV reciprocating tachycardia
      when they were in the supine position and in 17 when standing. The effective
      refractory period of the AV node markedly shortened, from 275 +/- 72 to 203 +/-
      30 ms (n = 16, p less than 0.005) after standing. The effective refractory period
      of the accessory pathway shortened slightly, from 293 +/- 75 to 278 +/- 77 ms (n
      = 8, p less than 0.005), after standing. AV node reentrant tachycardia was
      induced in 3 of the 11 patients with AV node reentrant tachycardia when they were
      in the supine position and in 6 when standing. The effective refractory periods
      of the slow pathway and fast pathway shortened markedly, from 293 +/- 72 to 216
      +/- 40 ms (n = 6, p less than 0.025) and from 416 +/- 85 to 277 +/- 50 ms (n =
      10, p less than 0.005), respectively, after standing. Plasma norepinephrine
      levels increased during standing both in patients with AV reciprocating and in
      those with AV node reentrant tachycardia (n = 11, p less than 0.005, n = 8, p
      less than 0.005, respectively). In conclusion, standing, which is associated with
      increased sympathetic tone, changed the electrophysiologic properties of the
      reentrant circuits, facilitating induction of AV reciprocating tachycardia and AV
      node reentrant tachycardia.

PMID- 1993790
TI  - A randomized double-blind crossover comparison of four rate-responsive pacing
      modes.
AB  - The aim of this study was to compare, both subjectively and objectively, four
      modern rate-responsive pacing modes in a double-blind crossover design. Twenty
      two patients, aged 18 to 81 years, had an activity-sensing dual chamber universal
      rate-responsive (DDDR) pacemaker implanted for treatment of high grade
      atrioventricular block and chronotropic incompetence. They were randomly
      programmed to VVIR (ventricular demand rate-responsive), DDIR (dual chamber
      demand rate-responsive), DDD (dual chamber universal) or DDDR (dual chamber
      universal rate-responsive) mode and assessed after 4 weeks of out-of-hospital
      activity. Five patients, all with VVIR pacing, requested early reprogramming. The
      DDDR mode was preferred by 59% of patients; the VVIR mode was the least
      acceptable mode in 73%. Perceived "general well-being," exercise capacity,
      functional status and symptoms were significantly worse in the VVIR than in dual
      rate-responsive modes. Exercise treadmill time was longer in DDDR mode (p less
      than 0.01), but similar in all other modes. During standardized daily activities,
      heart rate in VVIR and DDIR modes underresponded to mental stress. All rate
      augmented modes overresponded to staircase descent, whereas the DDD mode
      significantly underresponded to staircase ascent. Echocardiography revealed no
      difference in chamber dimensions, left ventricular fractional shortening or
      pulmonary artery pressure in any mode. Cardiac output was greater at rest in the
      dual modes than in the VVIR mode (p = 0.006) but was similar at 120 beats/min.
      Beat to beat variability of cardiac output was greatest in VVIR mode (p less than
      0.0001), with DDIR showing greater variability than DDD or DDDR modes (p less
      than 0.05). Mitral regurgitation estimated by Doppler color flow imaging was
      similar in all modes, but tricuspid regurgitation was significantly greater in
      VVIR than in dual modes (p less than 0.03). Subjects who preferred the DDDR mode
      and those who found the VVIR mode least acceptable had significantly greater
      increases in stroke volume when paced in the DDD mode than in the ventricular
      inhibited (VVI) mode at rest (22%) when compared with subjects who preferred
      other modes (2%, p = 0.03). No other objective variable was predictive of
      subjective benefit from any rate-responsive pacing mode. Thus, dual sensor rate
      responsive pacing (DDDR) is superior objectively and subjectively to single
      sensor (VVIR, DDIR and DDD) pacing and subjective benefit from dual chamber rate
      augmented pacing is predictable echocardiographically.

PMID- 1993791
TI  - The automatic implantable cardioverter-defibrillator: effect of patch polarity on
      defibrillation threshold.
AB  - An automatic implantable cardioverter-defibrillator (AICD) was implanted in 40
      patients with sudden cardiac arrest (n = 29), sustained monomorphic ventricular
      tachycardia (n = 10) or recurrent syncope (n = 1) who were unsuitable for direct
      ablative surgery or had had unsuccessful medical therapy. The effect of patch
      electrode polarity on the defibrillation threshold was prospectively evaluated.
      Two large epicardial patches were used. Initial polarity was selected at random.
      Ventricular fibrillation was induced by direct current and a preestablished
      defibrillation protocol employed to assess the minimal energy that would
      reproducibly defibrillate the heart. Nineteen patients had a lower defibrillation
      threshold with the inferior left ventricular patch as an anode and nine patients
      had a lower defibrillation threshold with this patch as a cathode. In general,
      the defibrillation threshold was lower when this patch was used as an anode than
      when it was used as a cathode (18 +/- 10 versus 22.6 +/- 12.2 J; p less than
      0.01). No preoperative variable predicted optimal polarity. Therefore, the effect
      of patch polarity on defibrillation threshold should be assessed in each patient
      at the time of AICD implantation so that the safety margin for satisfactory
      device function can be maximized.

PMID- 1993792
TI  - Dissection of the aorta associated with congenital malformation of the aortic
      valve.
AB  - The association of congenital aortic valve malformation and aortic dissection is
      analyzed. Over a 30 year period, 186 patients with non-iatrogenic aortic
      dissection were studied at necropsy. The aortic valve was tricuspid in 170
      (91.4%), bicuspid in 14 (7.5%) and unicuspid in 2 (1.1%). Among the 16 patients
      with aortic dissection and a congenitally malformed valve, the age at death
      ranged from 17 to 82 years (mean 52) and 13 (81%) were men. The entrance tear of
      the aortic dissection was located in the ascending aorta in all 16 patients with
      a malformed valve but in only 68% of those with a tricuspid aortic valve. The
      aortic valve was stenotic in 6 of the 16 patients with a congenitally malformed
      valve. Fatal rupture of the false channel occurred after acute ascending aortic
      dissection in each of the 11 patients (none with healed dissection) who did not
      have operative therapy for the dissection. Two of the 16 patients with a
      malformed valve compared with no patient with a tricuspid aortic valve had aortic
      isthmic coarctation. Histologic sections of aorta from 10 patients disclosed
      severe degeneration of the elastic fibers of the media in 9 patients. Thus, a
      congenitally malformed aortic valve appears to be present at least 5 times more
      frequently in adults with than in those without aortic dissection, and in our
      patients the entrance tear was always in the ascending aorta, which usually had
      severe loss of elastic fibers in its media.

PMID- 1993793
TI  - Surgery for Ebstein's anomaly: the clinical and echocardiographic evaluation of a
      new technique.
AB  - Ten consecutive patients (age range 4 to 44 years, mean 22) underwent surgical
      repair of Ebstein's anomaly by vertical plication of the right ventricle and
      reimplantation of the tricuspid valve leaflets. No patient died during or after
      operation. Intraoperative postbypass echocardiography documented a good result in
      nine patients but severe tricuspid regurgitation in one patient, who then
      underwent prosthetic valve replacement during a second period of cardiopulmonary
      bypass. Two of four patients who had had right ventricular papillary muscle
      dysfunction in the early postoperative period showed improved papillary muscle
      function with concomitant reduction of tricuspid regurgitation 6 months later.
      All patients were evaluated clinically and by echocardiography 2 to 23 months
      later. All patients showed clinical improvement, seven by one functional class
      and three by two classes. All were in sinus rhythm. The mean cardiothoracic ratio
      decreased by 6% (p less than 0.05). On bicycle ergometry performed in six
      patients, peak oxygen consumption exceeded 20 ml/kg per min in five. Tricuspid
      regurgitation diminished in eight patients (by three grades in two patients, by
      two grades in five and by one grade in one patient); it remained unchanged in
      two. Comparison of preoperative and postoperative pulsed Doppler flow velocities
      across the pulmonary valve showed an increase in the peak velocity of flow across
      the valve (mean 83 +/- 14 versus 97 +/- 11 cm/s, p less than 0.005) and a
      decrease in the time to peak velocity (mean 130 +/- 16 versus 91 +/- 23 ms, p
      less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1993794
TI  - The role of chronotropic impairment during exercise after the Mustard operation.
AB  - To better understand the role of chronotropic impairment on exercise performance
      after the atrial switch (Mustard) operation, 20 patients who had undergone this
      operation for uncomplicated d-transposition of the great arteries exercised to
      maximal volition using a 1 min incremental treadmill protocol. Heart rate, oxygen
      consumption, carbon dioxide production and minute ventilation were monitored
      continuously. Two-dimensional echocardiograms were obtained before testing to
      calculate the right ventricular inflow volume indexed to body surface area. All
      patients achieved maximal aerobic capacity based on their ventilatory patterns
      and respiratory exchange ratio. Maximal heart rate was reduced (175 beats/min;
      87% of predicted for age) and maximal oxygen consumption was decreased (31 ml/kg
      per min; 75% of predicted for age and gender). There was no correlation between
      maximal oxygen consumption and maximal heart rate. Right ventricular volume
      index, however, had a significant inverse correlation with maximal heart rate (r
      = -0.62, p less than 0.005). There was no correlation between right ventricular
      volume index and heart rate at rest. These results suggest that decreased maximal
      oxygen consumption in patients after the Mustard procedure is not a result of
      chronotropic impairment. Right ventricular dilation may be a compensatory
      response to chronotropic impairment.

PMID- 1993795
TI  - Effect of captopril, an angiotensin-converting enzyme inhibitor, in patients with
      angina pectoris and heart failure.
AB  - The effects of captopril and placebo were compared in 18 patients with chronic
      heart failure and angina pectoris with use of a double-blind crossover trial
      design. Symptoms were assessed by patient treatment preference, visual analogue
      scores and nitroglycerin consumption. Exercise performance was assessed using two
      different treadmill protocols of different work intensity with simultaneous
      measurement of oxygen consumption and by supine bicycle exercise and simultaneous
      radionuclide ventriculography. Arrhythmias were assessed by 48 h ambulatory
      electrocardiographic monitoring. Patients generally preferred placebo to
      captopril, and this appeared to be due to an increase in symptoms of angina with
      captopril. Treadmill exercise time on a high intensity protocol was shorter with
      captopril than with placebo; on a low intensity protocol, angina became a more
      frequent limiting symptom even though overall exercise performance was not
      changed. The heart rate-blood pressure product was reduced, but largely because
      of a reduction in blood pressure rather than in heart rate. During supine bicycle
      exercise, no differences in symptoms, exercise performance, ejection fraction or
      changes in blood pressure were noted and ventricular arrhythmias were reduced.
      Captopril does not appear to be clinically useful in alleviating angina pectoris
      in patients with heart failure, and this effect may be related to a decrease in
      coronary perfusion pressure. Nonetheless, desirable metabolic effects, a
      reduction in arrhythmias and potential effects on survival require further study
      of captopril in patients with both angina and heart failure.

PMID- 1993796
TI  - Effect of maintenance digoxin therapy on aerobic performance and exercise left
      ventricular function in mild to moderate heart failure due to coronary artery
      disease: a randomized, placebo-controlled, crossover trial.
AB  - Despite 200 years of use, the ability of digitalis glycosides to improve exercise
      capacity in patients with congestive heart failure remains controversial, partly
      because of imprecise end points and suboptimal study design. Therefore, this
      question was examined in 10 ambulatory patients (8 men and 2 women) aged 46 to 70
      years (mean 57.8) in sinus rhythm with mild to moderate chronic stable congestive
      heart failure due to coronary artery disease and systolic left ventricular
      dysfunction (ejection fraction 32 +/- 12). All underwent maximal treadmill
      exercise with respiratory gas analysis and upright cycle ergometry with gated
      radionuclide angiography after 4 weeks of digoxin or placebo therapy,
      administered in a randomized double-blind crossover protocol. Neither treadmill
      exercise duration (7.7 +/- 2.3 versus 7.3 +/- 2.7 min) nor peak oxygen
      consumption (18.7 +/- 3.7 versus 18.4 +/- 5.4 ml/kg per min) differed between
      digoxin and placebo regimens. However, the change in peak oxygen consumption
      induced by digoxin was inversely related to the peak oxygen consumption during
      placebo therapy (r = -0.64, p less than 0.05). At maximal treadmill effort, heart
      rate (138 +/- 16 versus 141 +/- 21 beats/min), oxygen pulse (10.3 +/- 2.1 versus
      9.9 +/- 2.2 ml/beat), ventilation (40.3 +/- 10.6 versus 42.0 +/- 10.8 liters/min)
      and ventilatory equivalent (29.4 +/- 4.8 versus 31.5 +/- 6.8) did not differ
      between digoxin and placebo treatment, although systolic blood pressure was
      higher during digoxin therapy (163.0 +/- 23.1 versus 153.2 +/- 25.3 mm Hg, p less
      than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1993797
TI  - Treatment of recurrent ischemia after thrombolysis and successful reperfusion for
      acute myocardial infarction: effect on in-hospital mortality and left ventricular
      function.
AB  - To determine the effect of treatment of recurrent ischemia after reperfusion for
      acute myocardial infarction on in-hospital mortality and left ventricular
      function recovery and to identify patients at highest risk of serious
      consequences in the event of recurrent ischemia in this setting, 405
      consecutively treated patients were studied retrospectively. All patients
      received intravenous thrombolytic therapy within 6 h of ST segment elevation
      documented infarction and had angiographic confirmation of their reperfusion
      status performed within 120 min of treatment. Three hundred three patients had
      successful reperfusion with or without rescue angioplasty and had no recurrent
      ischemia (group 1), 74 patients had initially successful reperfusion but
      subsequent recurrent ischemia (group 2) and 28 patients had failed reperfusion
      (group 3). The in-hospital mortality in groups 1 to 3 was 2.0%, 14.9% and 32.1%,
      respectively (p less than 0.001) and the change from baseline to prehospital
      discharge left ventricular ejection fraction was 1.2 +/- 9.3%, -0.8 +/- 8.7% and 
      4.3 +/- 5.3%, respectively (p = NS). Within the recurrent ischemia group (group
      2), multiple regression analysis found absence of cardiogenic shock at
      presentation (p = 0.002) and successful treatment initiated within 90 min of
      recurrent ischemia (p = 0.045) to be the only variables independently correlated
      with in-hospital survival. Later successful reperfusion was not associated with
      improved hospital survival. The timing and success of treatment did not affect
      recovery of global or regional left ventricular function in the patients with
      paired angiographic studies.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1993798
TI  - A paradigm for restenosis based on cell biology: clues for the development of new
      preventive therapies.
AB  - Angioplasty causes substantial injury to the coronary artery intima and media
      that is unrecognizable by angiography. On the basis of a substantial body of
      research in oncology and wound healing, it is hypothesized that restenosis is a
      manifestation of the general wound healing response expressed specifically in
      vascular tissue. The temporal response to injury occurs in three characteristic
      phases: inflammation, granulation and extracellular matrix remodeling. The
      specific expression of these phases in the coronary artery leads to intimal
      hyperplasia at 1 to 4 months. The major milestones in the temporal sequence of
      restenosis are platelet aggregation, inflammatory cell infiltration, release of
      growth factors, medial smooth muscle cell modulation and proliferation,
      proteoglycan deposition and extracellular matrix remodeling. Each step has
      potential inhibitors that could be used for preventive therapy. Resolution of
      restenosis, however, probably requires both creation of the largest possible
      residual lumen and substantial inhibition of intimal hyperplasia.

PMID- 1993799
TI  - Percutaneous support devices for high risk or complicated coronary angioplasty.
AB  - Indications for coronary angioplasty have expanded to include patients with
      unstable acute ischemic syndromes, severe multivessel coronary artery disease and
      impaired left ventricular function. Several mechanical approaches have been
      developed as adjuncts to high risk coronary angioplasty to improve patient
      tolerance of coronary balloon occlusion and maintain hemodynamic stability in the
      event of complications. These percutaneous techniques include intraaortic balloon
      counterpulsation, anterograde transcatheter coronary perfusion, coronary sinus
      retroperfusion, cardiopulmonary bypass, Hemopump left ventricular assistance and
      partial left heart bypass. The intraaortic balloon pump provides hemodynamic
      support and ameliorates ischemia by decreasing myocardial work; it may be
      inserted for periprocedural complications or before angioplasty in patients with
      ischemia or hypotension. Anterograde distal coronary artery perfusion may be
      accomplished passively through an autoperfusion catheter or by active pumping of
      oxygenated blood or fluorocarbons through the central lumen of an angioplasty
      catheter. Synchronized coronary sinus retroperfusion produces pulsatile blood
      flow via the cardiac veins to the coronary bed distal to a stenosis. Both
      perfusion techniques limit development of ischemic chest pain and myocardial
      dysfunction in patients undergoing prolonged balloon inflations. Percutaneous
      cardiopulmonary bypass provides complete systemic hemodynamic support which is
      independent of intrinsic cardiac function or rhythm and has been employed
      prophylactically in very high risk patients before coronary angioplasty or
      emergently for abrupt closure. These and newer support devices, while associated
      with significant complications, may ultimately improve the safety of coronary
      angioplasty and allow its application to those who would otherwise not be
      candidates for revascularization.

PMID- 1993800
TI  - Regional myocardial blood flow and left ventricular diastolic properties in
      pacing-induced ischemia.
AB  - The relation between left ventricular diastolic abnormalities and myocardial
      blood flow during ischemia was studied in eight open chest dogs with critical
      stenoses of the proximal left anterior descending and circumflex coronary
      arteries. The heart was paced at 1.7 times the heart rate at rest for 3 min. In
      dogs with coronary stenoses, left ventricular end-diastolic pressure increased
      from 8 +/- 1 to 14 +/- 2 mm Hg during pacing tachycardia (p less than 0.01) and
      16 +/- 3 mm Hg (p less than 0.01) after pacing, with increased end-diastolic and
      end-systolic segment lengths in the ischemic regions. Left ventricular diastolic
      pressure-segment length relations for ischemic regions shifted upward during and
      after pacing tachycardia in dogs with coronary stenoses, indicating decreased
      regional diastolic distensibility. In dogs without coronary stenoses, the left
      ventricular diastolic pressure-segment length relation was unaltered. Pacing
      tachycardia without coronary stenoses induced an increase in anterograde coronary
      blood flow (assessed by flow meter) in both the left anterior descending and
      circumflex coronary arteries, and a decrease in regional vascular resistance. In
      dogs with coronary stenoses, regional vascular resistance before pacing was
      decreased by 18%; myocardial blood flow (assessed by microspheres) was unchanged
      in both the left anterior descending and circumflex coronary artery territories.
      During pacing tachycardia with coronary stenoses, regional coronary vascular
      resistance did not decrease further; subendocardial myocardial blood flow distal
      to the left anterior descending coronary artery stenosis decreased (from 1.03 +/-
      0.07 to 0.67 +/- 0.12 ml/min per g, p less than 0.01), as did subendocardial to
      subepicardial blood flow ratio (from 1.04 +/- 0.09 to 0.42 +/- 0.08, p less than
      0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1993801
TI  - Pressure-length loop area: its components analyzed during graded myocardial
      ischemia.
AB  - The changes in total pressure-length loop area were compared with changes in
      effective shortening area, systolic lengthening area and postsystolic shortening
      area (defined with respect to end-diastolic and end-systolic lengths) of the
      pressure-length loop during myocardial ischemia in seven anesthetized dogs
      instrumented for measurement of left ventricular pressure and regional segmental
      wall motion (sonomicrometry) in the minor axis of the apical region of the left
      ventricle. Ischemia was induced by gradual tightening of a micrometer-controlled
      snare around the left anterior descending coronary artery, which supplied the
      apical myocardium. Data were obtained at normal flow, after critical constriction
      (loss of pulsatile coronary flow), mild ischemia (ischemia 1: onset of regional
      dysfunction, i.e., postsystolic shortening and mild hypokinesia) and moderate
      ischemia (ischemia 2: marked hypokinesia). At each stage, acute afterloading was
      performed by partially occluding the descending thoracic aorta. The pressure
      length loops were analyzed in terms of four areas: total loop area, effective
      shortening area, postsystolic shortening area and systolic lengthening area.
      Total loop area decreased only when marked hypokinesia was present (176 +/- 18.3
      mm Hg x mm at ischemia 2 versus 245.1 +/- 26.9 mm Hg x mm at ischemia 1, p less
      than 0.05). However, effective shortening area (98.2 +/- 0.8% of total loop area
      at baseline; 93.8 +/- 2.4% at critical constriction; 76.3 +/- 7.2% at ischemia 1;
      51.9 +/- 12.2% at ischemia 2) and postsystolic shortening area (1.8 +/- 0.8% of
      total loop area at baseline; 5.2 +/- 1.9% at critical constriction; 14.3 +/- 3/4%
      at ischemia 1; 23.8 +/- 5.1% at ischemia 2) changed significantly with each
      progressive stage of ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1993802
TI  - Modification of atrioventricular node transmission properties by intraoperative
      neodymium-YAG laser photocoagulation in dogs.
AB  - The purpose of this study was to test the feasibility of neodymium-yttrium
      aluminum-garnet (Nd-YAG) laser photocoagulation of the atrioventricular (AV) node
      to control the ventricular rate during rapid atrial rhythms without creating AV
      block. In 12 dogs on normothermic cardiopulmonary bypass, short laser pulses were
      delivered to an area between the coronary sinus orifice and the site of the most
      proximally recorded His deflection until second degree AV block occurred at a
      paced atrial rate of 200 beats/min. Long-term effects on AV node function were
      followed up for 3 months. Three animals developed chronic high grade AV block. In
      nine animals with preserved 1:1 conduction, the mean (+/- SEM) critical atrial
      cycle length resulting in AV node Wenckebach periodicity increased from 183 +/- 6
      to 261 +/- 24 ms (+43%), the mean RR interval during induced atrial fibrillation
      increased from 248 +/- 14 to 330 +/- 27 ms (+32%) and the shortest RR interval
      during atrial fibrillation increased from 215 +/- 11 to 275 +/- 20 ms (+28%).
      Laser effects were not reversed by isoproterenol infusion. Histologic examination
      of the irradiated area showed fibrotic changes in the AV node and fatty
      metamorphosis. This study suggests that 1) graded Nd-YAG laser photocoagulation
      of the AV node region in dogs results in long-term modification of anterograde AV
      node transmission properties; 2) 1:1 conduction during sinus rhythm usually
      remains preserved, but ventricular rate during rapid atrial rhythms is
      chronically reduced; and 3) progression to high grade AV block occurs in a
      minority of animals.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1993804
TI  - A key map.

PMID- 1993803
TI  - Follow-up of patients with low output, low gradient hemodynamics after
      percutaneous balloon aortic valvuloplasty: the Mansfield Scientific Aortic
      Valvuloplasty Registry.
AB  - Symptomatic patients with a low cardiac output and low aortic valve gradient have
      a poor prognosis but are at high risk for aortic valve surgery. The outcome of
      percutaneous balloon aortic valvuloplasty in this subgroup of patients is
      unclear. Therefore, 67 patients (group 1) underwent percutaneous balloon aortic
      valvuloplasty between December 1, 1986 and November 1, 1987 who had a low cardiac
      index (less than 2.5 liters/min per m2) and a low aortic valve gradient (less
      than or equal to 40 mm Hg) before the procedure. The results were compared with
      200 patients (group 2) who had a low cardiac index but not a low aortic valve
      gradient (greater than 40 mm Hg) before the procedure and who had similar
      baseline presenting symptoms. After balloon aortic valvuloplasty, there was a
      greater decrease in aortic valve gradient in patients in group 2 than in patients
      in group 1 (mean +/- SD -33.0 +/- 16.7 mm Hg and -14.6 +/- 6.9 mm Hg,
      respectively; p less than 0.001) although there was no significant difference in
      improvement in estimated aortic valve area (0.31 +/- 0.21 and 0.31 +/- 0.22 cm2,
      respectively; p = NS). In-hospital mortality was 11.9% for patients in group 1
      which was not significantly different from the 7.5% mortality for patients in
      group 2. However, the actuarial probability of survival at 12 months for patients
      who survived the initial hospitalization was 46% in group 1 and 64% in group 2 (p
      less than 0.05). Moreover, at follow-up (mean 8.8 months) 64% of surviving group
      1 patients displayed clinical improvement, compared with 70% of surviving group 2
      patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1993805
TI  - How and why the nose runs.

PMID- 1993806
TI  - The National Asthma Education Program attacks asthma.

PMID- 1993807
TI  - Lymphocytes and nonlymphoid cells in human nasal polyps.
AB  - Immunohistochemical stainings were performed on polyp specimens of 48 patients
      and on mucosal biopsy specimens of the middle and inferior turbinates of 23 and
      28 patients, respectively. Significantly more CD8+ (suppressor/cytotoxic) than
      CD4+ (helper/inducer) cells were found in the polyps. The number of CD2+, CD4+,
      and CD8+ lymphocytes in nasal polyps were very similar to the number in the
      macroscopically unaffected mucosa of the middle turbinates, whereas scores in the
      inferior turbinates were lower. In healthy subjects, the differences were
      smaller. CD22+ B cells were detected in varying numbers in the polyps in more or
      less organized clusters. Significantly more HLA-DR+ cells were found in polyps
      and middle turbinates than in the inferior turbinates. Eosinophils were found in
      moderate to large numbers in polyps of 77% of the patients. Mast cells and plasma
      cells were detected in moderate numbers, whereas neutrophils were found in 35% of
      the patients. In the middle and inferior turbinates varying but small numbers of
      eosinophils, mast cells, plasma cells, and neutrophils were found. In considering
      these findings, the role of chronic inflammation with T cell-dependent
      disturbances is discussed with regard to the pathogenesis of nasal polyps.

PMID- 1993808
TI  - Reduction of budesonide after a year of increased use: a randomized controlled
      trial to evaluate whether improvements in airway responsiveness and clinical
      asthma are maintained.
AB  - We have demonstrated recently that 1 year of regular inhaled budesonide use can
      produce substantial improvements in airway responsiveness accompanied by
      significant improvements in clinical asthma severity. The present study was
      designed to evaluate whether these improvements are maintained when the dose of
      budesonide is reduced. At the end of the original study, 28 subjects with asthma,
      who had been in the active-treatment arm of the study were randomized either to
      continue taking the dose of budesonide taken in the original study or to have the
      dose reduced. Airway responsiveness to methacholine, bronchodilator requirements,
      symptoms, and spirometry were assessed after 6 weeks and 3 months. During the 3
      months, no subject experienced an asthma exacerbation, and there was no evidence
      of change in airway responsiveness in subjects who had their steroids reduced
      (provocative concentration causing a 20% drop in FEV1; initial, 2.03 mg/ml;
      final, 1.91 mg/ml), and this change was not different from change in subjects
      maintained with a higher dose (initial, 3.02 mg/ml; final, 3.12 mg/ml) (p =
      0.39). Similarly, there was no evidence of any change in bronchodilator
      requirements (p = 0.89). However, after 3 months of reduced steroid use, there
      was a small decline in spirometry (FEV1 percent predicted: initial, 84.4%; final,
      81.5%), and this change was significantly different from change in subjects in
      whom steroids were not reduced (initial, 90.2%; final, 90.2%) (p = 0.002). At 3
      months, symptoms (predominantly sputum production) were also beginning to
      redevelop in the reduced budesonide group (p = 0.056).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1993810
TI  - Environmental exposure to cockroach allergens: analysis with monoclonal antibody
      based enzyme immunoassays.
AB  - Quantitative two-site monoclonal antibody (MAb)-based enzyme-linked immunoassays
      for two cockroach (CR) allergens, Bla g I and Bla g II, have been developed and
      used to measure allergen levels in house-dust samples. Dust collected from the CR
      infested homes of two patients with asthma from Charlottesville, Va.,
      demonstrated wide variation in the levels of Bla g I, depending on the location
      of dust collection. Dust from kitchen floors and cabinets contained 50-fold more
      allergen (mean, 10,755 U/gm of dust) than dust from bedrooms and upholstered
      furniture (mean, 204 U/gm). One hundred forty-five dust samples were collected
      from the bedrooms and living rooms of 22 children with asthma and 16 control
      subjects without asthma living in Atlanta, Ga. Twenty-seven of the 38 homes
      (17/22 children with asthma; 10/16 control subjects) had detectable Bla g I (4 to
      1340 U/gm of dust). Bla g II levels were assayed in 40 kitchen, bedroom, and
      living room samples from homes in Wilmington, Del. Highest levels of Bla g II
      were detected in kitchen-floor dust (300 U/gm of dust). Additionally,
      approximately 20% of homes with no visual evidence of CR infestation had
      significant levels of Bla g II in at least one dust sample (greater than 4 U/gm
      of dust). Our results demonstrate that CR may be an occult allergen in homes. The
      kitchen appears to be the primary site of CR-allergen accumulation, but
      significant CR-allergen levels can also be found at other sites in the home. The
      MAb-based assays can be used for quantitation of environmental exposure to CR
      allergens.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1993809
TI  - Mucus secretagogue production by a human macrophage hybridoma.
AB  - A pulmonary macrophage-monocyte-derived mucus secretagogue (MMS) oligopeptide has
      been previously reported to induce mucus secretion in an in vitro model system
      with human airway explants and secretory epithelial cells. To understand the
      possible role of macrophages in the regulation of secretion of mucus, our
      laboratory has used a series of human macrophage hybridomas that were generated
      by fusing an hypoxanthine guanine phosphoribosyl transferase-deficient
      promonocytic line, U937, with macrophages obtaining by maturing monocytes in
      Teflon bags. The cell lines were proven to be true hybridomas by acquisition of
      donor class I antigens, additional chromosomes, as well as macrophage specific
      (maximum velocity) not present on the U937 parent line. One clone, clone 63,
      produced large amounts of an oligopeptide with an approximate molecular weight of
      2000, which was identified from culture supernatants by ultrafiltration,
      chromatography, isoelectric focusing, and Western blot. Processed clone 63
      supernatant had biologic activity causing increased secretion of radiolabeled
      glycoconjugate in both cultured airways and secretory epithelial cells.
      Immunoblot analysis with a polyclonal rabbit antisera generated against MMS was
      positive, and Western blot analysis produced a band at approximately 2000
      daltons, consistent with the previously described MMS. MMS secretion could be
      stimulated by zymosan and lipopolysaccharide and inhibited by both cycloheximide
      and erythromycin. Dexamethasone had a different effect, appearing to stimulate
      MMS production intracellularly but inhibiting its release once it was
      synthesized. The availability of cloned hybridomas allows for study of the
      regulation of mucus secretagogue production as well as purification of molecular
      species and provides a valuable tool for the study of mucus secretion.

PMID- 1993811
TI  - Identification, quantitation, and purification of cockroach allergens using
      monoclonal antibodies.
AB  - A panel of murine IgG monoclonal antibodies (MAbs) was raised against German
      cockroach (CR) (Blattella germanica) extract and selectively screened to identify
      MAb directed against allergen(s) recognized by IgE antibodies. Sera from 28 CR
      allergic patients were used as sources of IgE antibodies to detect allergens
      "presented" by the MAb. Four clones (10A6, 3G12, 8F4, and 1D4) produced MAb to
      allergen(s) that bound IgE antibodies. Quantitative radioimmunoassays were used
      to compare levels of the MAb-defined allergens in CR extracts. MAb 10A6 reacted
      with a cross-reacting allergen that was detected in 9/14 CR species, including
      Blattella, Periplaneta, Blatta, Leucophea, and Supella spp, at concentrations of
      100 to 10,000 U/ml. In contrast, MAb 3G12, 8F4, and 1D4 were Blattella specific.
      The allergen defined by MAb 8F4 was purified by MAb affinity chromatography and
      size-exclusion by high-performance liquid chromatography. It is a 36 kd heat
      sensitive protein, isoelectric point, 5.2 to 5.4. Allergen 10A6 was partially
      purified by isoelectric focusing and high-performance liquid chromatography. It
      is a heat-stable, acidic protein (isoelectric point 3.15). Based on comparison of
      their properties with properties of previously described CR allergens, the
      allergens defined by MAb 10A6 and 8F4 have been provisionally designated
      Blattella germanica allergen I (Bla g I) and Blattella germanica allergen II (Bla
      g II), respectively. Assays of six commercial CR skin test extracts demonstrated
      a 200-fold difference in Bla g I levels (4.7 to 1085 U/ml) and only two extracts
      that contained detectable Bla g II (248 and 324 U/ml). The results demonstrate
      that MAb can be used to identify and define CR allergens and that the strategy of
      the use of MAb as a first step in allergen analysis and purification can be very
      effective, especially for poorly characterized allergen extracts.

PMID- 1993812
TI  - Alterations of muscarinic acetylcholine receptors in the nasal mucosa of allergic
      patients in comparison with nonallergic individuals.
AB  - Cholinergic nasal hyperresponsiveness in nasal allergy may be due to changes of
      the characteristics in muscarinic cholinergic receptors. Radioligand receptor
      binding and in vitro autoradiographic studies of nasal mucosa in nonallergic (NA)
      and allergic patients were performed to investigate this hypothesis. The
      heterogeneous NA group was subdivided into control individuals and patients with
      chronic sinusitis and vasomotor rhinitis. The 3H-(-)-Quinuclidinylbenzilate
      binding to muscarinic receptors in human nasal mucosa membranes was saturable and
      of high affinity in all groups. No significant differences could be demonstrated
      between the subgroups of the NA patients. In allergic patients the dissociation
      constants and receptor densities were significantly decreased in comparison with
      those of NA and with those of control individuals. No differences in agonist
      binding or coupling of the muscarinic receptor to the effector system via the G
      protein could be observed in allergic patients. In vitro autoradiographic
      experiments demonstrated specific 3H-(-)-Quinuclidinylbenzilate labeling of the
      glandular acini in NA and allergic patients. No specific labeling could be
      observed in the epithelium, blood vessels, or connective tissue. In conclusion,
      the increased sensitivity and decreased muscarinic receptor number may reflect
      the cholinergic-induced hypersecretion in nasal allergy but are probably too
      small to explain the complex allergic reaction.

PMID- 1993813
TI  - Bronchoalveolar lavage fluid mediator levels 5 minutes after allergen challenge
      in atopic subjects with asthma: relationship to the development of late asthmatic
      responses.
AB  - Inflammatory mediators have been implicated in the pathogenesis of human asthma
      and have been demonstrated to increase in bronchoalveolar lavage fluid during the
      time of the immediate asthmatic response (IAR) after allergen instillation in the
      lungs. However, the relationship of these mediators, measured early to the late
      asthmatic response (LAR), airway reactivity, and clinical asthma, is unknown. In
      the present study, we evaluated mediator levels in bronchoalveolar lavage fluid
      before and 5 minutes after allergen challenge from three subject groups: atopic
      subjects without asthma (N = 7), atopic subjects with asthma and without LAR [-)
      LAR) (N = 6), and atopic subjects with asthma and with LAR [+) LAR) (N = 6).
      Subjects with asthma were differentiated into subjects with and without LARs
      based on at least a 15% decrease in FEV1 between 3 to 8 hours postallergen
      inhalation. The mediators, prostaglandin D2 thromboxane B2 leukotriene C4 (LTC4),
      and histamine, were measured both before and after allergen instillation.
      Baseline prechallenge levels were similar, except in the case of LTC4. LTC4 was
      detectable at baseline significantly more frequently in the atopic subjects with
      asthma with and without LAR when these subjects were compared to the atopic
      subjects without asthma (nine of 12 detectable versus one of seven detectable).
      In all groups, significant increases in mediator levels were observed in the
      groups with asthma postallergen challenge, compared to the atopic subjects
      without asthma. Atopic subjects with asthma and without LAR had significantly
      higher levels of all four mediators after challenge than atopic subjects with
      asthma and with LAR and atopic subjects without asthma.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1993814
TI  - Effects of various barriers on platelet-activating factor-induced neutrophil
      chemotaxis.
AB  - Platelet-activating factor (PAF)-induced neutrophil migration across endothelial
      and epithelial barriers is an important event in inflammation. We compared the
      effects of PAF on human neutrophil migration through filters alone, and human
      umbilical vein endothelial and Madin-Darby canine kidney epithelial cells
      cultured on these filters. We found that the amount of PAF-induced neutrophil
      migration was barrier dependent. At low PAF concentrations, neutrophil migration
      through filters exceeded migration measured through either cellular barrier. As
      PAF concentrations increased to greater than or equal to 1 mumol/L, neutrophil
      migration through human umbilical vein endothelial cells often equaled or
      exceeded migration measured through filters alone. In contrast, significant
      neutrophil migration through Madin-Darby canine kidney cells was not observed
      until PAF concentrations exceeded 50 mumol/L. Thus, the intensity of PAF-induced
      neutrophil inflammatory processes is, in part, dependent on the barrier through
      which the neutrophils must migrate.

PMID- 1993816
TI  - Particle penetration into the automotive interior. I. Influence of vehicle speed
      and ventilatory mode.
AB  - Penetration of particulate aeroallergens into the interiors of two, new, similar
      Chrysler Corporation passenger vehicles (having no evidence of intrinsic
      microbial contamination) was studied on a large circular test track during
      periods of high pollen and spore prevalence. Impactor collections were obtained
      at front and rear seat points and at the track center during periods with (1)
      windows and vents closed and air conditioning on, (2) windows closed, vents open,
      and no air conditioning, and (3) air conditioner off, front windows open, and
      vents closed. These conditions were examined sequentially during travel at 40,
      50, 60, and 80 kph. Particle recoveries within the two, new, similar Chrysler
      Corporation passenger vehicles did not vary with the speed of travel, either
      overall or with regard to each of the three ventilatory modalities. In addition,
      collections at front and rear seat sampling points were comparable. Highest
      interior aeroallergen levels were recorded with WO, and yet, these levels
      averaged only half the concurrent outside concentrations at track center.
      Recoveries within the cars were well below recoveries obtained outside when
      windows were closed (both VO and AC modes). These findings suggest window
      ventilation as an overriding factor determining particle ingress into moving
      vehicles. Efforts to delineate additional determinants of exposure by direct
      sampling are feasible and would appear essential in formulating realistic
      strategies of avoidance.

PMID- 1993815
TI  - Comparison of cockroach allergenic activity in whole body and fecal extracts.
AB  - Previous studies have established cockroach allergens as important sensitizing
      agents in the induction/exacerbation of urban asthma. The present investigation
      compared saline extracts of American cockroach (Periplaneta americana) whole
      bodies and feces and German cockroach (Blattella germanica) whole bodies and
      feces as important sources of allergens. All extracts were tested before or after
      gel filtration on Sephadex G-75 columns (fraction 2) as previously described.
      Skin test studies of 69 subjects with asthma with extracts of American or German
      cockroaches demonstrated a significant correlation of reactivity to whole body
      and fecal extracts for both species. Direct RASTs of 13 sera from cockroach skin
      test-positive subjects were generally greater to both German whole body extracts
      (GWBEs) and German fecal extracts (GFEs) as compared to American whole body and
      fecal extracts. There was a good correlation of RAST reactivity to GWBE with GFE.
      RAST inhibition demonstrated that GFE contained most of the allergenic activity
      present in GWBE. These studies demonstrate the allergenic similarities of
      cockroach whole body and fecal extracts and suggest that cockroach feces are an
      important sensitizing agent in atopic asthma.

PMID- 1993817
TI  - Analyses of microvascular permeability in response to mediators of immediate
      hypersensitivity.
AB  - Mediator-induced changes in microvascular permeability were studied in rodent
      skin. To monitor these changes, Evan's blue dye, iodinated rat albumin and IgG,
      and tritiated neutral dextran molecules having different molecular radii were
      used. After intradermal injections of serotonin, histamine, and bradykinin, the
      degree of radiolabeled tracer efflux was determined by measuring the extent of
      blueing and the level of radioactivity in skin biopsy specimens. Although the
      mediators varied in potency on a molar basis (serotonin greater than bradykinin
      greater than histamine), the efflux resulting from each was similar. Furthermore,
      kinetic studies revealed that each of these vasoactive agents caused a marked but
      transient increase in macromolecular permeability that lasted less than 30
      minutes. To determine the pore size created and the effect of charge on the
      transudation of macromolecules into the interstitium, fractions of neutral
      [3H]dextrans with a known molecular size (average radii, 12 and 4.4 nm,
      respectively) were infused either singly or in combination with 125I-labeled rat
      albumin and/or IgG before intradermal injection of serotonin, histamine,
      bradykinin, or compound 48/80. Regardless of the mediator used, no differences
      could be demonstrated in macromolecular efflux, as indicated by either the
      molecular size of the charge of the tracer used. Thus, all mediators of immediate
      hypersensitivity reactions that were studied produce venular gaps greater than 12
      nm in addition to displaying similar vasopermeable characteristics.

PMID- 1993819
TI  - Contact allergy to topical budesonide.

PMID- 1993818
TI  - Cat removal and Fel d I levels in mattresses.

PMID- 1993820
TI  - Ketotifen in systemic mastocytosis--a response.

PMID- 1993821
TI  - The use of reservoir devices for the simultaneous delivery of two metered-dose
      inhalers.

PMID- 1993822
TI  - Language changes and Alzheimer's disease: a literature review.
AB  - 1. In Alzheimer's disease, the effect of cognitive changes on language and the
      ability to communicate and interact with others is profound. 2. Communication
      difficulties are a common problem identified by caregivers of demented
      individuals. Breakdown of communication can be frustrating and overwhelming for
      both patient and caregiver. 3. The deterioration of different linguistic features
      of language occurs at different rates, making it harder to identify deficits in
      the early phases of the disease. Mental status testing can give some objective
      measure of deficits. 4. Research is identifying explicit changes that occur in
      the language of Alzheimer's disease victims. Knowledge of these changes suggests
      strategies that can enhance communication.

PMID- 1993823
TI  - How knowledge and labeling of dementia affect nurses' expectations.

PMID- 1993824
TI  - Australian caregivers of family members with dementia.
AB  - This study of Australian caregivers revealed that sufferers of dementia were men
      and women who were cared for mainly by their spouses. A small group of caregivers
      had little or no personal physical and emotional support from others. Changes in
      health status related to the caregiving role was reported by 83% of the
      caregivers. There is a clear need to provide physical and emotional support for
      caregivers generally and for those with little or no support in particular.

PMID- 1993825
TI  - If not now, when?

PMID- 1993826
TI  - Leisure and the older black woman.
AB  - Older black women's leisure experiences have not been studied in the past. Their
      unique point of view comes from diverse social and cultural experiences
      punctuated by a lifetime of inequities. Their experiences were described in
      routine terms; they talked about making it through the day. Their losses led to a
      feeling of loneliness. They found refuge in affiliating with others at the church
      and senior centers. Church activities and the personal experience of worship
      provided a context for remaining independent as they aged.

PMID- 1993827
TI  - Universal precautions: how effective are they against methicillin-resistant
      Staphylococcus aureus?
AB  - 1. Because MRSA is commonly carried asymptomatically, colonized patients and
      caregivers are usually not recognized. During outbreaks, colonized and infected
      patients act as reservoirs and caregivers become transient carriers. 2. Because
      universal precautions and body substance isolation were originally developed in
      response to the AIDS epidemic to meet the safety needs of hospital caregivers,
      the use of universal precautions in extended care facilities should be further
      studied and refined. 3. In planning for effective training, enforcement, and
      compliance with universal precautions, it is essential that employees understand
      not only the importance of protecting themselves, but also the need to prevent
      cross-infection. 4. If a patient has an MRSA respiratory tract infection, the
      environment, including the air, may become heavily contaminated. Caregivers
      should wear masks to prevent nasal colonization.

PMID- 1993828
TI  - Localization of Na(+)-dependent active type and erythrocyte/HepG2-type glucose
      transporters in rat kidney: immunofluorescence and immunogold study.
AB  - Glucose is actively taken up from the glomerular filtrate into the tubule cells
      by the Na(+)-dependent active glucose transporter (GT), and passively crosses the
      basolateral membrane via facilitated diffusion GT. With the use of antibodies
      directed against two types of GTs, we show the immunocytochemical localization of
      the Na(+)-dependent active GT (SGLT1) and the erythrocyte/HepG2-type facilitated
      diffusion GT (GLUT1). For light microscopic observation, frozen sections were
      stained by the rhodamine labeling method. Counterstaining with fluorescein
      phalloidin and 4,6-diamidino-2-phenylindole dihydrochloride (DAPI) was employed
      to facilitate cell type identification. Immunogold staining was carried out on
      ultra-thin frozen sections for electron microscopy. The antibody to SGLT1 reacted
      with a 77 KD protein in immunoblotting of a kidney lysate. By
      immunocytochemistry, SGLT1 was localized in the microvillous plasma membrane in
      the apical brush borders of the cells of all three proximal tubule segments (S1,
      S2, and S3). The antibodies to GLUT1, a member of the facilitated diffusion GT
      family, were raised against human erythrocyte GT or synthetic oligopeptides
      derived from HepG2 GT, which reacted with a 48 KD protein in immunoblotting of
      the kidney lysate. GLUT1 was found at the basolateral plasma membranes of S3
      proximal tubule cells, cells of the thick limb of Henle's loop, and collecting
      duct cells. Combined with known physiological data, our findings suggest that
      SGLT1 in the apical plasma membrane of the proximal tubule cells is responsible
      for the Na(+)-dependent active reabsorption of glucose from the glomerular
      filtrate. GLUT1 in the basolateral plasma membrane of S3 cells may transport
      reabsorbed glucose to the blood vessels. GLUT1 in the basolateral plasma
      membranes of cells of the thick limb of Henle's loop and of the collecting duct,
      on the other hand, may nourish these metabolically active cells by facilitating
      the diffusion of extracellular glucose provided from blood through the
      basolateral side of the cells.

PMID- 1993829
TI  - Monoclonal antibodies recognize localized antigens in the eye and central nervous
      system of the marine snail Bulla gouldiana.
AB  - The eyes of the marine snail Bulla gouldiana act as circadian pacemakers. The
      eyes exhibit a circadian variation in spontaneous optic nerve compound action
      potential frequency in constant darkness, and are involved in controlling
      circadian rhythms in behavioral activity expressed by the animal. To initiate an
      investigation of the molecular aspects of circadian rhythmicity in the Bulla eye
      and to identify specific molecular markers in the nervous system, we raised
      monoclonal antibodies (MAb) to the eye and screened them for specific patterns of
      staining in the eye and brain. Several MAb recognize antigens specific to groups
      of neurons in the brain, whereas others stain antigens found only in the eye. In
      addition, some antigens are shared by the eye and the brain. The antigens
      described here include molecules that mark the lens, retina, neural pathways
      between the eye and the brain, specific groups of neurons within the central
      ganglia, and an antigen that is shared by basal retinal neurons (putative ocular
      circadian pacemaker cells) and glia. These molecular markers may have utility in
      identifying functionally related groups of neurons, elucidating molecular
      specializations of the retina, and highlighting pathways used in transmission of
      information between the retina and the brain.

PMID- 1993830
TI  - Synthesis of CDP-diacylglycerol by rat liver rough microsomes as visualized by
      electron microscopic autoradiography: relationship to GTP-stimulated membrane
      fusion.
AB  - Using detergent-free conditions of incubation for the analysis of liponucleotide
      synthesis, we compared GTP-dependent formation of CDP-diacylglycerol (CDP-DG) and
      membrane fusion in RNA-depleted rough microsomes from rat liver. After incubation
      of stripped rough microsomes (SRM) in the presence of GTP and [5-3H]-CTP,
      radioactivity was recovered in lipid extracts and identified by thin-layer
      chromatography as a single spot which co-migrated with CDP-DG. The nucleotide
      requirement for CDP-DG synthesis and that for membrane fusion were observed to be
      identical. We next carried out an electron microscopic autoradiographic analysis
      on incubated membranes to determine the site of incorporation of [5-3H]-CTP.
      Silver grains were observed directly over the unilamellar membranes of natural
      vesicles. In confirmation of the biochemical data, quantitation of silver grain
      density indicated more grains over membranes incubated in the presence of GTP
      than over those incubated in the absence of this nucleotide. For membranes
      incubated in the presence of GTP, the grain density was similar over fused and
      unfused membranes in the same preparation. When SRM were incubated with the
      enzyme co-factors required for synthesis of phosphatidylinositol, a GTP
      independent membrane fusion was observed by both transmission and freeze-fracture
      electron microscopy. Together with the biochemical and autoradiographic data,
      this suggests that phospholipid metabolism may be activated by GTP and lead to
      the fusion of RER membrane.

PMID- 1993832
TI  - The road to publication is sometimes paved with bad intentions.

PMID- 1993831
TI  - Staphylococcal enterotoxin B: immunolabeling and visualization of target cells.
AB  - Binding of staphylococcal enterotoxin B (SEB) to cultured cells and to tissue
      sections containing presumed target sites was detected by use of an
      immunofluorescence sandwich technique. A triple sandwich with successive
      incubations of SEB, rabbit anti-SEB, and fluorescein-conjugated goat anti-rabbit
      secondary antibody was applied to samples. Binding of SEB to rat basophilic
      leukemia (RBL) cells, mast cells of rat dorsal skin, and cells of leukocyte
      enriched human plasma was observed. Our results point out and reinforce the
      reported involvement of SEB in various biological effects that appear to
      implicate leukocytes, either as mast cells residing in tissues or as white cells
      circulating in the bloodstream.

PMID- 1993833
TI  - BrdUrd labeling of S-phase cells in testes and small intestine of mice, using
      microwave irradiation for immunogold-silver staining.

PMID- 1993834
TI  - Immunogold-silver staining method at the transmission electron microscopic level.

PMID- 1993835
TI  - Thin cryosections for improved resolution.

PMID- 1993836
TI  - Effect of cyclosporin A on lymphopoiesis. III. Augmentation of the generation of
      natural killer cells in bone marrow transplanted mice treated with cyclosporin A.
AB  - The effects of cyclosporin A (CsA) on the generation of NK cells were studied
      using syngeneic bone marrow transplanted mice subsequently treated with CsA
      (BMT/CsA mice). In contrast to a severe reduction in T cells that was reported
      previously, these mice exhibited a marked enhancement of splenic NK activity. The
      enhanced NK activity was mediated by NK1.1+, Thy-1- cells as assessed by antibody
      plus complement treatment, and was concomitant with an absolute increase in the
      numbers of NK1.1+ cells as assessed by flow cytometry. Because the depletion of
      host-derived, mature NK cells by injection of anti-asialo GM1 antibody before
      bone marrow reconstitution did not affect the enhancement of NK activity, CsA
      appeared to augment the generation of NK cells from bone marrow precursors. To
      investigate a possible relationship between the enhancement of NK activity and
      the maturational arrest of T cells in the thymus induced by CsA, mice were
      thymectomized, followed by irradiation, bone marrow reconstitution, and CsA
      treatment. These mice exhibited as strong enhancement of splenic NK activity as
      BMT/CsA mice, suggesting that the CsA-induced effect on NK cells is distinct from
      its effect on T cell development in the thymus. Taken together, these results are
      the first demonstration of the positive effect of CsA on NK cell generation and
      may be of importance in clinical bone marrow transplantation.

PMID- 1993837
TI  - Characterization of autoantibody-secreting B cells in mice undergoing stimulatory
      (chronic) graft-versus-host reactions. Identification of a CD44hi population that
      binds specifically to hyaluronate.
AB  - This study was undertaken to identify and isolate the pathophysiologically
      important B cell subpopulation which is activated to Ig secretion and
      autoantibody production in stimulatory (chronic) graft-vs-host (GVH) reactions.
      We recently demonstrated that IL-5 stimulation in vitro induces the appearance of
      a distinct CD44hi Ialow CD45Rlow B cell subpopulation that has aquired the
      ability to bind to hyaluronate (HA), one of the ligands for CD44, and that this B
      cell subpopulation is enriched in both proliferative and Ig-secretory responses.
      In the present report, CD44 expression was examined in B cells which were
      activated in the course of stimulatory GVH reactions. Compared with normal mice,
      B cells from mice undergoing stimulatory GVH reactions contained a novel CD44hi B
      cell subpopulation which exhibited enhanced binding to HA. The CD44hi HA-adherent
      B cell subpopulation from GVH mice spontaneously secreted large amounts of Ig,
      particularly IgG, including autoantibody specific for ssDNA. These findings
      demonstrate that CD44 expression distinguishes those B cells that are activated
      in vivo in the course of GVH to proliferate and differentiate into Ig-secreting
      cells. These CD44hi, HA-adherent, cells may play a prominent role in the
      hypergammaglobulinemia and immune complex glomerulonephritis that occur during
      chronic GVH reactions.

PMID- 1993839
TI  - An analysis of synthetic peptide restriction by HLA-DR alleles in T cells from
      human subjects, naturally sensitized by Streptococcus mutans.
AB  - T cells from most human subjects show significant in vitro proliferative
      responses to a 185-kDa surface Ag from Streptococcus mutans as well as to
      synthetic peptides derived from the sequence of a Mr 3800 streptococcal Ag. T
      cells from subjects expressing each of the alleles from DR1 to DR7 responded to
      synthetic peptides of 17 or 21 amino acid residues. Furthermore, inhibition
      studies with mAb to HLA class I and class II Ag showed that the DR Ag was a
      restriction molecule for the proliferative responses. Mouse L cells transfected
      with DR1, DR2, DR4, DR5, and DR7 were used to confirm the permissive nature of
      the responses. An analysis of the fine specificity of the responses showed that
      the minimum peptides capable of stimulating T cells from subjects with different
      DR types varied by one or two residues. For DR2 and DR3 the shortest peptide was
      residues 6-15, an additional serine (residue 5) was required for DR1 and DR7 and
      an aspartic acid (residue 4) for DR4, DR5, and DR6. Successful oral-mucosal
      bacterial colonisation in humans, by a largely commensal Streptococcus, might be
      associated with the permissive nature of the HLA-DR restriction of the response
      to a major streptococcal cell surface peptide. The peptide recognised in
      association with the HLA-DR molecule may induce an immune response that prevents
      central entry of the organism from the peripheral mucosal site.

PMID- 1993838
TI  - Tissue factor expression in endothelial cell/monocyte cocultures stimulated by
      lipopolysaccharide and/or aggregated IgG. Mechanisms of cell:cell communication.
AB  - A human umbilical vein endothelial cell (EC)/monocyte (MC) coculture system was
      used to dissect cell:cell interactions associated with production of procoagulant
      activity (PCA) in response to two common stimuli of intravascular coagulation in
      vivo (LPS and immune complexes). We found that the presence of MC at a ratio of 1
      MC:10 EC increased the sensitivity of EC to LPS by 4 logs and the maximal
      response approximately 20-fold. Aggregated IgG alone did not stimulate the
      system, but in the presence of small amounts of LPS (1 to 10 ng/ml) aggregated
      IgG was a powerful stimulus. More than 90% of the PCA was tissue factor as shown
      by clotting studies and mRNA analysis. PCA was not produced by either cell alone
      under the conditions of study, but was produced in large amounts when the EC and
      MC were cocultured. The supernatant from the coculture stimulated virgin EC, but
      not MC, to synthesize tissue factor. The major factor in the supernatant was IL-1
      beta as shown by measuring IL-1 beta, IL-1 alpha, and TNF-alpha in supernatants
      and by blocking the production of PCA by preincubation of supernatants with anti
      cytokine antibodies. Small amounts of TNF-alpha were present in the supernatant
      but anti-TNF-alpha did not inhibit PCA production. Studies using recombinant
      cytokines established that IL-1 beta was the most potent of the cytokines tested,
      that cytokines potentiated each other, and that the results could be explained in
      quantitative terms by the amounts of IL-1 beta measured. These data emphasize
      that cell:cell interactions are likely to modulate procoagulant events in vivo in
      the presence of both LPS and immune complexes, and that IL-1 beta may be an
      important cytokine in these events.

PMID- 1993840
TI  - IL-1 induces ornithine decarboxylase in normal T lymphocytes.
AB  - IL-1 alpha regulation of ornithine decarboxylase (ODC) was examined in T cells
      because IL-1 is a costimulus for T cell proliferation and ODC is a critical
      enzyme in the metabolic events associated with cellular proliferation. In the
      present study, we demonstrate that IL-1 alpha induces ODC mRNA and ODC enzyme
      activity in T cells. Unlike many IL-1 actions on T cells, this did not require a
      costimulus from the TCR, IL-1 alone being sufficient to induce ODC. The mechanism
      of IL-1 induction of ODC probably operates at several levels, including
      transcription, mRNA stability, and translation. Previous studies have shown that
      IL-1 prepares T cells for replication by increasing the production of c-jun, c
      fos, c-myc, growth factors, growth factor receptors, and the response to growth
      factors. From the present study, ODC induction can be added to the list of IL-1
      induced replicative machinery in T cells.

PMID- 1993841
TI  - Tumor necrosis factor-alpha inhibits the competence signal delivered by HIV to
      normal B cells.
AB  - Polyclonal B cell activation is commonly observed in HIV-infected patients. The
      coordinate delivery of a number of signals is required for B cell response. This
      work was designed to better define the role of HIV in the first steps of normal
      human B cells activation. We show that the infectious virus or recombinant
      envelope proteins can render B cells responsive to the growth-promoting effect of
      several T cell-derived IL, IL-2, IL-4, and low m.w. (12-kDa) BCGF. HIV acts in
      the absence of monocytes and on different populations of B cells. The competence
      signal can be provided by recombinant gp160 envelope protein. CD4 molecule is not
      involved in the interaction of HIV with B cells. In addition, we demonstrate that
      tumor necrosis factor alpha has no promoting activity when B cells are
      preactivated by HIV and it can suppress the response of HIV-preactivated B cells
      to IL-2, IL-4, and 12-kDa BCGF. Thus, the HIV envelope can deliver an early
      signal to normal B cells and modulate B cell response to physiologic signals. The
      possible relevance of this phenomenon to the immune defect observed in HIV
      patients is discussed.

PMID- 1993843
TI  - Generation of monoclonal antibodies to murine IL-1 beta and demonstration of IL-1
      in vivo.
AB  - The role of murine IL-1 beta in vitro and in vivo has not been defined. We
      describe here the production of neutralizing and immunoprecipitating mAb and
      polyclonal antibodies specific for murine IL-1 beta and their application to a
      characterization of the murine IL-1 beta protein. Immunization of either hamsters
      or rabbits with the recombinant mature form of murine IL-1 beta emulsified in CFA
      elicited antisera and hamster mAb that only recognized denatured IL-1 beta. In
      contrast, immunization with rIL-1 beta adsorbed to alum resulted in the
      generation of neutralizing and immunoprecipitating rabbit and hamster antisera
      and hamster mAb. All of the mAb recognize both the pro-form of IL-1 beta and the
      mature bioactive form produced by cultures of murine peritoneal macrophages.
      Using these antibodies, we demonstrate that approximately half of the IL-1
      activity present in supernatants of LPS-treated cultured mouse macrophages is
      composed of IL-1 beta. Additionally, IL-1 beta as well as IL-1 alpha can be
      detected in the plasma of LPS-treated mice. These studies, therefore, demonstrate
      the production of IL-1 beta both in vitro and in vivo.

PMID- 1993842
TI  - Cytokine mRNA are preferentially increased relative to secretory granule protein
      mRNA in mouse bone marrow-derived mast cells that have undergone IgE-mediated
      activation and degranulation.
AB  - The levels of mRNA that encode a number of cytokines have been reported by
      several laboratories to be increased in mouse mast cells after their IgE-bearing
      receptors have been cross-linked with Ag. In this study, we have compared the
      mRNA levels for Fc epsilon RI alpha, three cytokines (IL-6, granulocyte
      macrophage CSF, and TNF-alpha), actin and three secretory granule-localized
      proteins (carboxypeptidase A, proteoglycan peptide core, and a generic serine
      protease) in mouse bone marrow-derived mast cells (BMMC) before and after IgE
      mediated activation and degranulation to determine the kinetics and specificity
      of mRNA induction. An antigen concentration of approximately 10 ng/ml was optimal
      for the release of histamine from IgE-sensitized BMMC and for the generation and
      release of a cytokine that was functionally and immunochemically identical to TNF
      alpha. In kinetic experiments, the levels of TNF-alpha, IL-6, and granulocyte
      macrophage CSF mRNA increased greater than 23-fold 0.5 to 1 h after activation.
      As assessed by in situ hybridization, virtually all BMMC contained detectable
      proteoglycan peptide core mRNA before and after exposure to Ag, but only
      approximately one-half of the Ag-treated cells in the culture contained IL-6 mRNA
      1 h after activation. There was a slight transient increase at 4 h in the level
      of proteoglycan peptide core mRNA, but no increase in the levels of those highly
      expressed mRNA that encode actin, Fc epsilon RI alpha, carboxypeptidase A, and
      serine protease. Thus, despite the remarkable increment in the levels of the
      transcripts that encode cytokines in BMMC after IgE-mediated, Ag-dependent
      activation, the levels of those transcripts that encode a plasma membrane
      localized recognition receptor and several constituents of the secretory granule
      remain essentially unchanged. The failure to increase substantially the level of
      protease and proteoglycan peptide core mRNA in mast cells after the
      activation/secretion response suggests that regranulation of mast cells is a slow
      process.

PMID- 1993844
TI  - Lipopolysaccharide, tumor necrosis factor-alpha, and IL-1 beta prevent programmed
      cell death (apoptosis) in human peripheral blood monocytes.
AB  - Human peripheral blood monocytes progressively lose viability when cultured in
      the absence of serum, cytokines, or other stimuli. In this study, we investigated
      whether monocyte death results from membrane damage (i.e., necrosis) or
      internally regulated processes [i.e., programmed cell death (PCD) or apoptosis].
      Our results clearly indicated that monocytes die by PCD when cultured without
      stimulation. Death was associated with fragmentation of DNA into integer
      multiples of approximately 200 bp, a decrease in cell size, condensation of the
      nucleus and cytoplasmic organelles, and membrane blebbing, all of which are
      cardinal features of PCD. Monocytes exposed to nonphysiologic conditions such as
      acidic media (pH 4.2), 56 degrees C for 30 min, or freezing and thawing were
      killed without concomitant DNA fragmentation, indicating that DNA fragmentation
      was not a result of cell death per se. Addition of Escherichia coli LPS, a potent
      monocyte activating agent, in concentrations as low as 0.1 ng/ml caused a marked
      increase in monocyte survival and prevented DNA fragmentation. Moreover,
      exogenous human rTNF-alpha or IL-1 beta also prevented PCD, suggesting that PCD
      is regulated by certain cytokines released from LPS-stimulated monocytes. The
      results indicate that in the absence of appropriate stimulation, monocytes are
      programmed to undergo a sequence of molecular events leading to cell death.
      Regulation of PCD may be an important homeostatic mechanism for controlling the
      number of monocytes available to respond to infection, wound healing, and tumor
      growth.

PMID- 1993845
TI  - Administration of IL-7 to mice with cyclophosphamide-induced lymphopenia
      accelerates lymphocyte repopulation.
AB  - Lymphopenia was induced in mice by a single injection of cyclophosphamide. IL-7
      or a control protein were administered to the mice twice daily and the
      cellularity and composition of the spleen, lymph node, bone marrow, and thymus
      were determined at various time points thereafter. In comparison to the control
      cyclophosphamide-treated mice, animals receiving cyclophosphamide and IL-7 had an
      accelerated regeneration of splenic and lymph node cellularity. There was no
      significant difference in the rate of recovery of the bone marrow and thymus of
      the control and IL-7-treated mice. Assessment of the pre-B cell compartment
      revealed a dramatic increase in total pre-B cell numbers in the spleen and bone
      marrow of the IL-7-treated mice as measured by both flow microfluorimetry and a
      pre-B cell colony-forming assay. This was followed in a few days by a significant
      increase in surface IgM+B cell numbers to levels above normal values in both the
      spleen and lymph node. IL-7 administration to cyclophosphamide-treated mice also
      resulted in an accelerated recovery of peripheral CD4+ and CD8+ cell numbers in
      the spleen and lymph node. The numbers of CD8+ cells were increased by twofold
      over normal levels in cyclophosphamide-treated mice receiving IL-7. Myeloid
      recovery was determined in cyclophosphamide treated mice by assessing the numbers
      of CFU-granulocyte-macrophage and Mac 1+ cells. There was no significant
      difference in myeloid recovery between cyclophosphamide-treated mice receiving IL
      7 or control protein. These results suggest that administration of IL-7 after
      chemical-induced lymphopenia may have therapeutic benefits in shortening the
      period required to achieve normal lymphoid cellularity.

PMID- 1993846
TI  - A dominant idiotype in the antibody response against the influenza virus
      hemagglutinin. Serum and in situ analyses.
AB  - PY206 is an Id associated with a BALB/c murine mAb described as being specific
      for the influenza A virus hemagglutinin. However, production of this Id by BALB/c
      mice immunized with influenza is low. This report shows that the PY206 Id is a
      dominant component of the anti-influenza antibody response in C57BL/6J strain
      mice infected intranasally with the influenza A/Hong Kong/168/(H3N2)[R] X-31
      virus. High PY206 Id expression was linked to the IgHb Ig allotype locus. PY206
      Id+ antibody-forming cells were identified in situ in cryostat sections of
      lymphoid tissues and idiotypic heterogeneity was identified among PY206+ B cells.
      Uninfected adult C57BL/6J mice had PY206 Id in their serum that lacked influenza
      binding specificity. In situ analysis of prenatal and neonatal spleen of
      uninfected C57BL/6J mice showed that the expansion of PY206 Id+ B cells occurred
      early in development. PY206+ cells were demonstrated in the lungs of influenza
      infected mice but not in normal mice, establishing the capability to study this B
      cell population in the lung. This model offers the opportunity to manipulate the
      anti-influenza A virus hemagglutinin B cell response and to study the
      proliferation and migration of influenza-specific B cells in their native tissue
      environments.

PMID- 1993847
TI  - Direct identification of the putative surface IgM receptor-associated molecule
      encoded by murine B cell-specific mb-1 gene.
AB  - The B cell-specific mb-1 gene was recently reported to encode a putative surface
      glycoprotein with CD3-like structural properties. Hombach et al. suggested and
      presented evidence to show that this mb-1 gene encodes the 34-kDa membrane
      glycoprotein (B34 or IgM-alpha) associated with IgMR molecule. To identify the mb
      1 gene product directly in B cells, affinity-purified MB-1-specific antibody was
      prepared by immunization of rabbits with synthetic MB-1 oligopeptide.
      Immunoprecipitation in combination with two-dimensional diagonal gel
      electrophoresis analysis revealed that this antibody detected a B cell-specific
      surface glycoprotein that is very similar to the IgM-alpha (B34) protein
      described by Hombach et al. However, MB-1 protein exists usually as the monomeric
      form on the surface of B cells, in contrast to IgM-alpha, which was detected as
      the dimeric (IgM-alpha/IgM-alpha or IgM-alpha/Ig-beta) protein. We also found
      that MB-1 protein is already expressed on the sIgM- pre-B cell lymphoma, which
      might suggest an alternative functional role of this B cell-specific MB-1 protein
      in B cell differentiation. The molecular identity of MB-1 protein and IgM-alpha
      (B34) is discussed.

PMID- 1993848
TI  - Binding to native proteins by antipeptide monoclonal antibodies.
AB  - mAb raised against synthetic peptides derived from cholera toxin, myohemerythrin,
      and sickle hemoglobin were analyzed by both solid-phase and solution-phase
      methods. Antipeptide mAb against cholera toxin (mAb TE32 and TE33), against
      myohemerythrin (mAb B13I2, B13C2, and B13F2), and against sickle hemoglobin (mAb
      HuS-1 and HuS-2), had been previously described and used for vaccine development,
      structural characterization, or identification of a specific antigenic
      determinant, and each was apparently capable of binding both peptide and native
      Ag. In this study, all were found to bind whole protein when tested against
      immobilized Ag in a standard solid-phase assay (ELISA), yet none of the
      antibodies recognized the Ag in its true native form, failing to bind when tested
      in several solution-phase assay systems, including size exclusion HPLC. This
      discrepancy may be the result of modifications of the epitope created by
      interaction and possible denaturation of the protein on the solid-phase matrix.
      As a consequence, binding of these antibodies to peptides, either immobilized or
      in solution, or to immobilized protein, cannot be used to infer that the peptide
      has assumed a conformation that corresponds to that of the cognate sequence in
      the native protein. A re-evaluation of binding data that relates antipeptide mAb
      to native structural characteristics may be necessary.

PMID- 1993850
TI  - Evidence for the functional binding in vivo of tumor rejection antigens to
      antigen-presenting cells in tumor-bearing hosts.
AB  - Spleen cells of BALB/c mice bearing a syngeneic CSA1M fibrosarcoma were treated
      with anti-Thy-1.2 antibody plus C, yielding a T cell-depleted, APC-containing
      fraction. The APC-containing fraction was first tested for its capacity to
      present exogenous modified-self or another tumor (Meth A) Ag after in vitro
      pulsing. The results showed comparable Ag-presenting capacities to those obtained
      by APC-containing fraction from normal spleen cells, indicating that APC function
      is not affected in tumor-bearing mice. We next examined whether APC from CSA1M
      bearing mice bind endogenously generated CSA1M tumor Ag onto its surfaces to
      stimulate tumor-specific T cells. Five rounds of inoculation of APC-containing
      fraction from CSA1M-bearing mice without further in vitro pulsing resulted in the
      induction of potent anti-CSA1M immune resistance. The involvement of anti-CSA1M T
      cells in the induction of anti-CSA1M immunity was excluded by the fact that the
      in vivo immunity was excluded by the fact that the in vivo immunity was delivered
      by Thy-1+ cell-depleted, but not by Thy-1+ cell-enriched fractions of spleen
      cells from CSA1M-bearing mice. Moreover, the failure of Sephadex G10-passed
      spleen cells to deliver anti-CSA1M resistance demonstrated the absolute
      requirement of APC for inducing the in vivo immunity. Finally, this in vivo
      resistance was found to be tumor specific, because APC fractions from CSA1M
      bearing and Meth A-bearing BALB/c mice induced immune resistance selective
      against the corresponding tumor cell challenge. These results indicate that APC
      from tumor-bearing hosts can not only exert unaffected APC function against
      exogenous Ag, but also function to present tumor Ag generated endogenously in the
      tumor-bearing state and to produce tumor-specific immunity in vivo.

PMID- 1993851
TI  - Collected papers on the significance of multiple human alpha-interferon subtypes
      from Journal of Interferon Research 1982-1990.

PMID- 1993849
TI  - Inducible nuclear expression of NF-kappa B in primary B cells stimulated through
      the surface Ig receptor.
AB  - Constitutive expression of NF-kappa B has been associated with developmental
      maturity in B cells on the basis of studies using continuously growing cell lines
      and plasmacytomas; however, little is known about the behavior of NF-kappa B in
      primary, mature B cells. In the present work, the regulation of NF-kappa B
      expression was studied by analyzing subcellular fractions of adult murine splenic
      B cells with the electrophoretic mobility shift assay using a kappa B-containing
      oligonucleotide. Although nuclear extracts from resting B cells contained kappa B
      binding activity, additional kappa B-binding activity was present in cytosolic
      fractions in a form that became apparent after treatment with detergent.
      Competition analysis indicated that the DNA binding activity detected by
      electrophoretic gel mobility shift assay was specific for the kappa B motif, and
      UV photo-cross-linking showed the molecular size of kappa B-binding protein to be
      similar to that of the DNA binding subunit of NF-kappa B. Nuclear expression of
      kappa B-binding activity was markedly induced by treatment of B cells with
      phorbol ester or with LPS. Most notably, kappa B-binding activity was induced
      after surface IgR cross-linking, and the mechanism of this induction involved
      PKC. Further, anti-Ig-induced activity was superinduced in the presence of
      cycloheximide. These results indicate that nuclear NF-kappa B is rapidly induced
      as a result of B cell stimulation, and further suggest that NF-kappa B may play a
      specific role in mature B cells after ligand binding to surface Ig distinct from
      its postulated developmental role as a stage-specific factor involved in kappa
      enhancer function.

PMID- 1993852
TI  - Intravascular retention and renal handling of purified natural and
      intramolecularly cross-linked hemoglobins.
AB  - Plasma half time of unmodified hemoglobin (UHb) and two intramolecularly cross
      linked hemoglobins (alpha alpha XL and beta beta XL) was measured in anesthetized
      rats after an intravenous bolus of 20 mg.100 gm.-1 To rule out the possibility
      that differences among plasma half times might be caused by differences in acute
      effects on renal excretory function, glomerular filtration rate (GFR) and
      effective renal plasma flow (ERPF) were measured simultaneously with plasma half
      time. Experiments were also done to determine whether higher doses (60 to 100 mg
      1.100 gm-1) of these compounds had a delayed effect (48 hours) on GFR or ERPF.
      Massive urinary excretion of UHb occurred; however, only 1% of the alpha alpha XL
      and none of the beta beta XL was excreted. Plasma half time of alpha alpha XL and
      beta beta XL averaged 3.3 hours, or four times longer than UHb. In no case did a
      decrease in GFR or ERPF occur. Instead, a transient increase in GFR, ERPF, urine
      flow, and systemic blood pressure was seen. Similar increases occurred after
      albumin administration, suggesting expansion of vascular volume as the initiating
      factor. Renal functions at 48 hours after 60 to 100 mg.100 gm-1 of UHb, alpha
      alpha XL or beta beta XL were not different from control (albumin). Intratubular
      hemoglobin casts or intravascular precipitates were not evident in acute or 48
      hour studies. At 48 hours Perls' staining material was found in one alpha alpha
      XL specimen at 3 hours after administration. Perls' staining material was present
      in renal tubule cells in all but the albumin-treated kidneys.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1993853
TI  - Evidence from endothelium of gastric absorption of heparin and of dextran
      sulfates 8000.
AB  - Heparin, hydrogenated dextran sulfate 8000 (Usherdex 8), and dextran sulfate 8000
      were administered to rats, and the total drug was separated and determined in
      endothelium and plasma. A large amount of each drug was recovered from
      endothelium 2.4 and 6 minutes after intravenous injection. This accounted for the
      drug missing from plasma. The drugs in water were placed in the stomach by
      catheter. All three drugs were recovered from the endothelium and identified
      unchanged by electrophoresis and specific staining. The amounts that were
      recovered at 2.4 and 6 minutes were equivalent to most of the drug administered.
      Thus heparin, Usherdex 8, and dextran sulfate 8000 enter the body immediately on
      oral administration. At longer time intervals after intravenous and oral
      administration, much of each drug was not demonstrable in endothelium by the
      method used. Some drug could be detected in endothelium after 4 hours. After oral
      administration, plasma levels of each drug were rarely more than 0.5% of the
      dose. Formalin-alcohol was applied to the jugular veins of anesthetized rats to
      produce a thrombus, (see Blake et al. J Clin Path 1959;12:118-22) and the drugs
      were immediately introduced into the stomach. Four hours later the injured veins
      were inspected for thrombi. Incidence of thrombotic plug was 80% in rats that
      received saline solution, 4% with Usherdex 8, 0% with dextran sulfate 8000, and
      0% with heparin. Usherdex 8, dextran sulfate 8000, and heparin demonstrate low,
      moderate, and high in vitro anticoagulant activity, respectively.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1993855
TI  - The prevalence of allergic bronchopulmonary aspergillosis in patients with
      asthma, determined by serologic and radiologic criteria in patients at risk.
AB  - Allergic bronchopulmonary aspergillosis, a hitherto uncommon but potentially
      crippling complication of asthma, occurs at an unknown prevalence in the United
      States. Using both modern serologic criteria complete with a history of asthma
      and radiologic findings, we were able to make the diagnosis of allergic
      bronchopulmonary aspergillosis in 28 of 100 consecutive patients with asthma who
      had immediate cutaneous reactivity to Aspergillus fumigatus and who were seen in
      an outpatient setting. Problems associated with use of less comprehensive
      criteria for this diagnosis are discussed.

PMID- 1993854
TI  - Changes in glutathione concentration in hypothermically perfused dog kidneys.
AB  - A loss of glutathione from the kidney can cause increased sensitivity to oxygen
      free radical-induced injury. In this study we investigated the effects of kidney
      preservation on glutathione and how various glutathione precursors affect
      glutathione concentration in the dog kidney. During 5-day continuous machine
      perfusion of the kidney at 5 degrees C, a loss of glutathione from the cortex
      tissue was seen (24% +/- 1% glutathione remained after 5 days). Perfusion with
      reduced glutathione (GSH, 3 mmol/L) suppressed this loss (77% +/- 11% of
      glutathione remained after 5 days). Oxidized glutathione (GSSG) did not prevent
      the loss of glutathione. The addition of the three amino acids that make up
      glutathione (glycine, glutamic acid, and cysteine, 3 mmol/L each) also suppressed
      the loss of glutathione (82% +/- 13% remained at 5 days). The glutathione
      precursor, thioproline, a cysteine delivery compound, in combination with glycine
      and glutamic acid (3 mmol/L each), stimulated the synthesis of glutathione in the
      kidney during hypothermic perfusion (137% +/- 23% of control values at 5 days).
      The increase in tissue glutathione stimulated by GSH or other precursors was
      sensitive to the glutathione synthetase inhibitor, buthionine sulfoximine. This
      indicated the existence of active glutathione metabolism even at 5 degrees C in
      perfused kidneys. This study showed that in kidney preservation a loss of
      glutathione occurred that could be suppressed by the addition of various
      precursors for glutathione synthesis. The loss of glutathione from preserved
      kidneys may be one cause of posttransplant renal injury that could be prevented
      by use of the appropriate glutathione precursors.

PMID- 1993856
TI  - Cross-linked hemoglobin solution as a resuscitative fluid after hemorrhage in the
      rat.
AB  - Intramolecularly (alpha-alpha) cross-linked hemoglobin has been reported to have
      oxygen transport properties similar to those of whole blood. The present study
      evaluated the efficacy of diaspirin alpha-alpha cross-linked hemoglobin solution
      as a resuscitation fluid, with heart rate, mean arterial pressure, and
      transcutaneous oxygen tension as the study parameters. Rats were bled and
      approximately one third of their total blood volume (20 ml/kg) was removed while
      they were anesthetized; they were then resuscitated with 14% hemoglobin solution.
      Animals that received either 10 mg/kg (n = 10) or 20 mg/kg (n = 10) of hemoglobin
      solution responded quickly and positively to the infusions: mean arterial
      pressure (which had dropped to less than 40% of prehemorrhage levels) returned to
      baseline within 2 minutes of initiating infusion; by 4 minutes, the mean arterial
      pressures of the hemoglobin-infused groups were significantly higher (p less than
      or equal to 0.05) than those in both the autologous shed blood (n = 8) and
      lactated Ringer's (n = 10) groups. The heart rate and transcutaneous oxygen
      tension responses in both the half-volume and full-volume replacement hemoglobin
      groups matched the response to autologous shed blood throughout the hour of
      observation. The favorable hemodynamic response to infusion of cross-linked
      hemoglobin solution after hemorrhage suggests that this material is comparable to
      autologous shed blood and superior to lactated Ringer's solution as a
      resuscitative fluid as assessed in this model.

PMID- 1993857
TI  - Factor XIII and its substrates, fibronectin, fibrinogen, and alpha 2-antiplasmin,
      in plasma and urine of patients with nephrosis.
AB  - Plasma and urine concentrations of factor XIII and its circulating substrates
      (fibronectin, fibrinogen, and alpha 2-antiplasmin) were measured in a group of 36
      patients with nephrotic syndrome. The results were compared with those obtained
      in a group of 32 normal volunteers (control group) and 12 patients with end-stage
      renal disease (ESRD). A mild but significant reduction in plasma level and an
      abnormal urinary excretion of alpha 2-antiplasmin was found in the nephrotic
      group. Plasma concentrations of factor XIII, fibronectin, and fibrinogen were
      significantly elevated in patients with nephrosis. In contrast, patients with
      ESRD showed no significant difference in the plasma concentrations of either
      factor XIII, fibronectin, or alpha 2-antiplasmin and only a modest elevation of
      fibrinogen when compared with normal controls. No significant correlation was
      found between serum creatinine concentration and plasma levels of factor XIII and
      its circulating substrates in the nephrotic group. No measurable quantities of
      factor XIII and only small quantities of fibronectin were found in the urine of
      patients with nephrosis. Elevation of plasma factor XIII, fibronectin, and
      fibrinogen concentrations in the nephrotic group is considered to be the result
      of a combination of increased synthesis and possibly contracted intravascular
      distribution of these macromolecular proteins in the face of their negligible
      urinary losses. The presence of the observed abnormalities in the nephrotic group
      and their absence in the non-nephrotic ESRD group tends to exclude renal failure
      as a cause of these abnormalities. Although the clinical significance of these
      abnormalities is uncertain, they can potentially contribute to the thrombophilic
      diathesis and platelet hyperaggregability in nephrotic syndrome.

PMID- 1993859
TI  - "These troublesome concretions": a study on calculus vesicae at the Medical
      Department of Transylvania University, 1836-1850.

PMID- 1993858
TI  - Biophysical characteristics of hemoglobin intramolecularly cross-linked and
      polymerized.
AB  - Hemoglobin modified by intramolecular cross-linking with 2-nor-2-formylpyridoxal
      5'-phosphate (NFPLP) has potential application as an oxygen-carrying plasma
      expander with improved vascular retention time (threefold) and oxygen
      transporting properties compared to native hemoglobin. Under some conditions a
      further prolongation is required. In this study polymerization of the purified
      modified hemoglobin (HbNFPLP) with glutaraldehyde was investigated. The influence
      of the degree of polymerization on the iso-oncotic concentration and the
      viscosity of the polymerized Hb-NFPLP (polyHbNFPLP) was investigated with three
      products polymerized to an increasing extent. Exchange transfusions in rats
      followed by gel filtration analyses of plasma samples provided information on the
      vascular retention time of four separate polymer fractions (i.e., monomers,
      dimers, trimers/tetramers, and polymers). The vascular retention time of these
      fractions correlated with their size. For lightly and highly polymerized HbNFPLP
      we found fivefold and sevenfold increases, respectively, compared to the
      retention time for native hemoglobin. This finding and the different shapes of
      the clearance curves suggested a different clearance mechanism from the vascular
      system for the monomer and polymer fractions. By polymerizing HbNFPLP the oxygen
      affinity was enhanced (oxygen half-saturation pressure shifted from 45 to 22 mm
      Hg), and it appeared to be independent of the degree of polymerization. Because
      hemoglobin was undetectable in the urine of the rats after the exchange
      transfusions, no accumulation of polyHbNFPLP will occur in the tubules of the
      kidney.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1993860
TI  - Why I don't teach high school chemistry.

PMID- 1993861
TI  - "Old" livers don't regenerate in a week.

PMID- 1993862
TI  - Major histocompatibility gene products and human immunodeficiency virus
      infection.
AB  - In the present paper we analyze the role of major histocompatibility gene
      products, the human leukocyte antigens, in the pathophysiology of the acquired
      immunodeficiency syndrome. No association has been found between human leukocyte
      antigen (HLA) frequencies and human immunodeficiency virus type 1 (HIV 1)
      infection, whereas significant associations have been reported in some
      populations between some HLA haplotypes and the appearance of either
      opportunistic infections or secondary cancers. With regard to the human leukocyte
      class I antigens, their role as restriction elements in presenting HIV 1 to virus
      specific cytotoxic T lymphocytes seems to be established. An increase in the
      serum levels of their soluble forms that correlate with disease stage has also
      been demonstrated. These circulating molecules could interfere with the immune
      response to HIV 1 and could contribute to the development of the
      immunodeficiency. Antigenic similarities have been detected between human
      leukocyte class II antigens and HIV 1 envelope proteins. These homologies could
      explain both the presence in some HIV-positive sera of anti-HLA class II
      antibodies that mediate the lysis of CD4(+)-HLA class II+ T cells and the false
      positive reaction of some HIV-negative sera, which contain anti-HLA class II
      antibodies, in tests for HIV 1 antibodies. Reduced levels of some complement
      factors (the human leukocyte class III antigens) have been detected in HIV
      infected subjects. These defects could play a role in the progression of the
      disease and affect both the clearance of HIV 1 and complement-mediated antibody
      responses. The data reported in this review suggest that HLA antigens may be
      involved in several steps of the immune deficiency of HIV-infected subjects and
      thus contribute to the pathophysiology of acquired immunodeficiency syndrome.

PMID- 1993863
TI  - Purification, characterization and serological detection of virus-like particles
      associated with banana bunchy top disease in Australia.
AB  - Isometric virus-like particles, 18 nm in diameter, have been isolated from banana
      (Musa spp.) affected by bunchy top disease in Australia. Banana bunchy top
      disease-associated virus-like particles (BBTV) banded as a single component with
      buoyant density of 1.28 to 1.29 g/ml in Cs2SO4 and sedimented at about 46S in
      isokinetic sucrose density gradients. The A260/A280 of purified preparations was
      about 1.33. A single coat protein of Mr 20,500 was identified with antibodies to
      BBTV particles from Australia. Single-stranded DNA of about 1 kb as well as ssRNA
      smaller than 0.45 kb was also associated with the particles. A polyclonal
      antiserum to BBTV, suitable for use in ELISA, was prepared. Stability and
      antigenicity of purified BBTV was impaired by storage at pH greater than or equal
      to 8.5 and freezing at -20 degrees C without protectants. BBTV was detected by
      double antibody sandwich-ELISA with monoclonal and polyclonal antibodies, in
      field-infected banana plants, single aphids from an infective colony, and in
      experimentally aphid-inoculated banana plants. After transmission of BBTV
      particles by aphids from a banana bunchy top disease-affected to an uninfected
      banana plant, the disease was induced and BBTV was detected by ELISA in
      symptomatic leaves only. BBTV isolates from Australia, Taiwan, People's Republic
      of China, Tonga, Western Samoa and Hawaii were found to be serologically related,
      which suggests a common aetiology for the disease.

PMID- 1993864
TI  - Virus-like particles associated with banana bunchy top disease contain small
      single-stranded DNA.
AB  - Virus-like particles were purified from banana plants with banana bunchy top
      disease. These particles were isometric with a diameter of 18 to 20 nm and a
      density of 1.28 to 1.30 g/ml in caesium sulphate. Associated with these particles
      were an ssDNA of about 1 kb and one major protein of Mr 20,100. DsDNA was
      synthesized from nucleic acid extracts from these particles and cloned. One
      clone, pBT338, hybridized specifically (i) with sap extracts from plants infected
      with banana bunchy top virus (BBTV) but not with sap extracts from healthy plants
      and (ii) with the small ssDNA in nucleic acid extracts from infected plants and
      virus-like particles. Banana bunchy top disease was transmitted from infected to
      healthy bananas by aphid inoculation and it was demonstrated that the small ssDNA
      was transmitted with the disease. It is probable that these particles represent
      the virions of BBTV containing small ssDNA and that the virus resembles
      subterranean clover stunt virus more than any other known virus.

PMID- 1993865
TI  - Resistance in Solanum brevidens to both potato virus Y and potato virus X may be
      associated with slow cell-to-cell spread.
AB  - A series of experiments was carried out to investigate the nature of the
      resistance of the wild potato species, Solanum brevidens, to potato virus X (PVX)
      and potato virus Y (PVY). In vitro inoculation of leaf protoplasts of S.
      brevidens and the virus-susceptible dihaploid S. tuberosum genotype PDH40 with
      PVX or PVY using polyethylene glycol showed that protoplasts of both species were
      similar in susceptibility. However, examination of protoplasts prepared from the
      leaves of S. tuberosum and S. brevidens inoculated 2 to 5 weeks earlier showed
      that the percentage of PVX- and PVY-infected leaf cells of S. tuberosum were,
      respectively, 45- to 100-fold and about 1000-fold greater than the percentage of
      infected leaf cells of S. brevidens. These results suggest that resistance in S.
      brevidens to both PVX and PVY could be associated with slow cell-to-cell spread
      rather than with slow virus replication.

PMID- 1993866
TI  - Unexpected sequence diversity in the amino-terminal ends of the coat proteins of
      strains of sugarcane mosaic virus.
AB  - The sequence of the 3'-terminal 1343 nucleotides of the SC strain of the
      sugarcane mosaic virus (SCMV-SC) genome was compared with the 1376 nucleotides at
      the 3' terminus of maize dwarf mosaic virus B (MDMV-B). The SCMV-SC sequence
      includes an open reading frame which codes for the viral coat protein of 313
      amino acids (nucleotides 157 to 1116), followed by a 3' non-coding region of 235
      nucleotides and a poly(A) tail. The MDMV-B sequence codes for the capsid protein
      (nucleotides 157 to 1139) of 328 amino acids and has a 3' non-coding region of
      236 nucleotides. The coat protein of SCMV-SC has 92% identity with that of MDMV-B
      except for the region between amino acid residues 27 and 70 of SCMV-SC. This
      region of SCMV-SC is smaller (44 residues) than the equivalent region in MDMV-B
      (59 residues) and has only 22% identity with the MDMV-B sequence. Possible
      mechanisms for the generation of this sequence diversity are discussed. Despite
      this diversity, the sequence identities of both the major part of the coat
      proteins and the 3' non-coding regions confirm the proposal, based on previously
      described serological data, that SCMV-SC and MDMV-B are strains of SCMV.

PMID- 1993867
TI  - Infectivity of plasmids containing brome mosaic virus cDNA linked to the
      cauliflower mosaic virus 35S RNA promoter.
AB  - Full-length biologically active cDNAs of brome mosaic virus genomic RNAs 1, 2 and
      3 were constructed by joining cDNA fragments. The cDNAs were constructed so that,
      at the 5' ends, unique SnaBI sites were present at the site of initiation of
      transcription. The cDNAs were inserted between a modified cauliflower mosaic
      virus (CaMV) 35S RNA promoter and terminator regions derived from CaMV DNA, and
      cloned into pUC18. When a mixture of the plasmid DNAs was inoculated onto
      Chenopodium hybridum leaves, local lesions appeared 5 to 6 days later. However,
      no symptoms appeared in similarly inoculated barley plants. Plasmid cDNAs with
      extra sequences at the 5' end were infectious but RNAs transcribed from cDNAs
      with similar sequences were not.

PMID- 1993868
TI  - In vitro processing of the RNA-2-encoded polyprotein of two nepoviruses: tomato
      black ring virus and grapevine chrome mosaic virus.
AB  - In vitro translation of RNA-2 of each of two closely related nepoviruses, tomato
      black ring virus (TBRV) and grapevine chrome mosaic virus (GCMV), in a rabbit
      reticulocyte lysate resulted in the synthesis of single polypeptides of 150K and
      146K respectively. Processing of these polyproteins occurred after the addition
      of translation products of homologous RNA-1. The positions of the cleavage
      products within the polyproteins were determined. From the N to the C terminus,
      Mr values for the proteins were 50K, 46K and 59K for TBRV and 44K, 46K and 56K
      for GCMV. TBRV RNA-1 translation products also cleaved the polyproteins encoded
      by GCMV RNA-2 which suggests that the cleavage sites in the two polyproteins are
      similar.

PMID- 1993869
TI  - Alfalfa mosaic virus RNA3 mutants do not replicate in transgenic plants
      expressing RNA3-specific genes.
AB  - The RNA3 of alfalfa mosaic virus (AIMV) encodes the P3 protein and the viral coat
      protein (CP). RNA3 molecules transcribed in vitro replicated in protoplasts and
      plants when inoculated in mixtures with AIMV RNA1, RNA2 and CP. Transcripts with
      a deletion or inversion in the P3 gene replicated well in protoplasts but not in
      transgenic plants transformed with the P3 gene. Transgenic plants expressing the
      CP gene became infected after inoculation with a mixture of RNA1, RNA2 and wild
      type RNA3 transcripts without addition of CP to the inoculum. Transcripts with a
      deletion in the CP gene replicated at a reduced level in protoplasts but not in
      CP-transformed plants. This suggests that P3 and CP are both required for cell-to
      cell spread of AIMV and that mutations in the inoculum RNA could not be
      complemented in trans by the wild-type chimeric nuclear genes.

PMID- 1993870
TI  - Shortened forms of beet necrotic yellow vein virus RNA-3 and -4: internal
      deletions and a subgenomic RNA.
AB  - Beet necrotic yellow vein virus RNA-3 and RNA-4, produced as full-length
      biologically active transcripts in vitro, can undergo spontaneous internal
      deletions when inoculated onto Chenopodium quinoa leaves along with RNA-1 and -2.
      The deletion process is specific, giving rise to only a few major species, and
      can be rapid; deleted forms appear after only one or two passages in leaves. In
      one of the shortened forms of RNA-4, the deletion precisely eliminated one copy
      of a 15 nucleotide (nt) direct sequence repeat from the full-length prototype
      sequence, suggesting that 'copy-choice' switching of the replicase-template
      complex from one repeat to the other during RNA replication was responsible for
      the generation of this deletion. The deletion found in a major shortened form of
      RNA-3, on the other hand, did not occur near sequence repeats but began with GU
      and ended with AG like a nuclear intron sequence. Thus it is possible that the
      deleted sequence has been removed by splicing. However, two other deletions that
      were characterized were not associated with either of these types of sequence
      feature. An approximately 600 nt 5'-terminally truncated non-encapsidated form of
      RNA-3 was also detected in infected plant tissue. The evidence suggests that it
      is a subgenomic RNA derived from RNA-3.

PMID- 1993871
TI  - Cell-free translation and identification of the replicative form of Nudaurelia
      beta virus RNA.
AB  - Larvae of the pine emperor moth, Nudaurelia cytherea capensis, infected with
      Nudaurelia beta virus (N beta V) consistently contained one species of dsRNA.
      This dsRNA was the correct size to be the replicative form of the N beta V genome
      and, in Northern blots, it hybridized with 32P-end-labelled virion RNA. Other
      smaller dsRNAs were obtained in a non-reproducible manner but these had no
      sequences in common with the genomic probe; no dsRNAs were observed in extracts
      from virus-free larvae. Cell-free translation of N beta V RNA resulted in the
      synthesis of only one major polypeptide, of Mr about 71,000, which could not be
      precipitated by an anti-N beta V serum.

PMID- 1993872
TI  - Immunoelectron microscopic examination of Orgyia pseudotsugata multicapsid
      nuclear polyhedrosis virus-infected Lymantria dispar cells: time course and
      localization of major polyhedron-associated proteins.
AB  - Immunoelectron microscopy was employed to examine the temporal expression and
      localization of two proteins involved in baculovirus polyhedron assembly
      (polyhedrin and p10) of Orgyia pseudotsugata multicapsid nuclear polyhedrosis
      virus (OpMNPV) in infected Lymantria dispar cells. In addition, the association
      of p10 with the polyhedron envelope (PE) protein was studied. The major capsid
      protein (p39) was also examined to investigate the association of virion
      structural proteins with polyhedron formation. In infected cells, p39 did not
      show a concentrated association with any infected-cell structures other than
      nucleocapsids and appeared to be randomly distributed over the nucleocapsid
      surface. Likewise, polyhedrin showed no major concentrations outside of
      developing or mature polyhedra. The p10 antibody cross-reacted with a protein
      associated with condensed chromosomes in uninfected cells. In infected cells, p10
      is a component of the body of fibrillar structures. The PE protein has been shown
      to accumulate around the periphery of fibrillar structures. Cells infected with a
      polyhedrin-minus virus expressing the beta-galactosidase gene under the control
      of the polyhedrin promoter were examined to determine whether the lack of
      polyhedra would influence the localization of major polyhedron-associated viral
      proteins. High concentrations of PE protein accumulating on the periphery of
      fibrillar structures appeared to be the major difference from wild-type virus
      infected cells. The beta-galactosidase protein appeared to be distributed
      throughout the nucleus and cytoplasm, in contrast with the specific localization
      of the viral proteins.

PMID- 1993873
TI  - Nucleotide sequence and transcript mapping of the HindIII F region of the
      Autographa californica nuclear polyhedrosis virus genome.
AB  - The organization of genes in the 2.95 kb EcoRI-SalI fragment (0.7 to 3.0 map
      units) located within the HindIII F region of the Autographa californica nuclear
      polyhedrosis virus genome was studied by a combination of DNA sequencing,
      Northern blot analysis, S1 mapping and primer extension analysis. In addition to
      the two divergent overlapping transcripts [leftward early (ES1) and rightward
      late (ES2)] previously reported, a third transcript which is present at 18 h p.i.
      and which also runs leftward, overlapping ES1 by 1600 nucleotides (nt) at the 3'
      end, was mapped to this region. The DNA sequence revealed the presence of three
      open reading frames (ORFs) of significant length. ORF-1 and ORF-2 correspond to
      the leftward transcripts, and code for potential polypeptides of 151 and 329
      amino acids, respectively. ORF-3 which codes for a potential polypeptide of 167
      amino acids is located on the opposite strand in a region for which no transcript
      mapping data are available. However, the conserved late gene promoter/cap site
      sequence (ATAAG) is present 23 nt upstream of the start of ORF-3.

PMID- 1993874
TI  - Restricted mumps virus infection of cells derived from normal human joint tissue.
AB  - Mumps virus (MuV) is known to be associated with acute arthritis and may also
      have a role in chronic inflammatory joint disease. The mechanism of induction of
      joint inflammation is not known but may be associated with direct invasion of
      joint tissue. To investigate the possibility of persistent intra-articular
      infection, the interaction of MuV with primary cells from normal human joint
      tissue was examined. These mixed cultures of synovial membrane cells and
      chondrocytes were found to be semi-permissive to the virus; only a small
      proportion of cells (5 to 20%) were infected and produced low titres of progeny
      virions. In addition, little viral antigen was detected on the cell surface
      relative to that found on Vero cells. This restricted infection of synovial
      membrane cells was related to a severely decreased synthesis of the viral
      glycoproteins, fusion and haemagglutinin-neuraminidase, and the membrane protein
      in comparison to the levels found in Vero cells. Persistent infections were
      readily established and could be maintained for 2 to 3 months. During the first
      month, the infection remained highly focal and supernatant viral titres were low.
      Thereafter both the percentage of infected cells and viral titres increased until
      finally the cultures were killed. No evidence was obtained for the generation of
      temperature-sensitive mutants or defective interfering particles during long-term
      infection, but the persistent virus derived from the cultures gave cloudy plaques
      and induced no fusion in Vero cells until passaged. This study has shown that
      human synovial tissue cells have the intrinsic ability to support MuV replication
      and persistence which may be important in the pathogenesis of mumps arthritis.

PMID- 1993875
TI  - Respiratory syncytial virus heterogeneity during an epidemic: analysis by limited
      nucleotide sequencing (SH gene) and restriction mapping (N gene).
AB  - The genes encoding the small hydrophobic (SH) proteins of a series of respiratory
      syncytial (RS) virus strains were amplified using the polymerase chain reaction,
      cloned and sequenced. Analysis of the SH gene sequences from 12 RS virus strains
      isolated between 1956 and 1989 confirmed the homogeneity of the two subgroups. A
      and B, previously defined serologically. Although there is only 76% deduced amino
      acid sequence identity of SH proteins between subgroups, there was little
      variation in deduced amino acid sequences within the subgroups; nucleotide
      homologies within the subgroups ranged between 93% and 99%. Forty-two isolates of
      RS virus from a single epidemic season (autumn/winter 1989) were also examined to
      determine their relatedness. For these isolates regions of both the SH and
      nucleocapsid protein genes of each isolate were amplified and these regions were
      further analysed by direct nucleotide sequencing or restriction mapping. It was
      possible to discriminate at least six different lineages (or substrains) of RS
      virus circulating at the same time and in the same locality.

PMID- 1993877
TI  - Proteolytic maturation of vaccinia virus core proteins: identification of a
      conserved motif at the N termini of the 4b and 25K virion proteins.
AB  - Three structural proteins (4a, 4b and 25K) located within the virion core of
      vaccinia virus are cleavage products of precursor polypeptides (P4a, P4b and
      P25K) synthesized late in viral infection. Pulse-chase labelling experiments
      revealed that cleavage of the core proteins lags considerably behind precursor
      synthesis and that processing requires continuous protein synthesis. The N
      terminal sequences of 4b and 25K, but not 4a, were determined by microsequencing
      core proteins isolated from purified virions. Comparison of these data with the
      predicted amino acid sequence of P4b and P25K revealed a conserved Ala-Gly-Ala
      motif flanking the apparent N termini of both proteins, as well as several
      additional sequence similarities between the P4b and P25K precursors both
      upstream and downstream of the putative cleavage site. The Ala-Gly-Ala tripeptide
      signal was also found in the same region of the amino acid sequences of the
      homologous proteins of fowlpox virus.

PMID- 1993876
TI  - Stable expression of rabies virus glycoprotein in Chinese hamster ovary cells.
AB  - The rabies virus glycoprotein (G protein) has several important functions and is
      a major antigenic stimulus of the host immune system following rabies virus
      infection or vaccination. We developed a model system for studying the role of N
      linked glycosylation in the intracellular transport and antigenicity of this
      molecule. The full-length cDNA of the G protein of the ERA strain of rabies virus
      was inserted into the eukaryotic shuttle vector pSG5 and then stably transfected
      into wild-type Chinese hamster ovary (CHO) cells and mutant CHO cell lines
      defective in glycosylation. Transfected wild-type CHO cells expressed the G
      protein (detected by immunofluorescence) on the cell surface in a manner similar
      to rabies virus-infected cells. The transfected wild-type CHO cells were shown by
      immunoprecipitation to produce a protein of 67K that comigrated with the fully
      glycosylated G protein isolated from virus-infected cells or purified virions.
      Treatment of the transfected cell lines with tunicamycin completely blocked
      surface expression and resulted in the intracellular accumulation of the G
      protein, suggesting that the presence of N-linked oligosaccharides is important
      for transport of this glycoprotein to the plasma membrane. The G protein cDNA was
      also expressed in the lectin-resistant CHO cell lines Lec 1, Lec 2 and Lec 8. In
      these cells initial N-linked glycosylation does occur, but later steps in
      processing of the oligosaccharides are blocked. In each case, the G protein was
      expressed on the surface of lectin-resistant CHO cells in a similar manner to
      expression on wild-type CHO cells. This suggests that various different N-linked
      oligosaccharide structures support intracellular transport of this glycoprotein.
      Thus, stably transfected CHO cell lines will provide a useful model system for
      further studies of the role of N-linked glycosylation in trafficking and
      antigenicity of the rabies virus G protein.

PMID- 1993879
TI  - Production of polyclonal antibodies against the S and preS2 regions of woodchuck
      hepatitis virus: lack of detectable low glycosylated preS2 protein (GP33) in sera
      from infected animals.
AB  - Polyclonal antibodies directed against the preS2 and S domains of the woodchuck
      hepatitis virus (WHV) envelope proteins were prepared using synthetic peptides
      and fusion polypeptides as immunogens. They were tested by immunoblotting and
      immunoprecipitation of infected woodchuck sera and lysates of a eukaryotic cell
      line expressing WHV envelope proteins. Only one anti-peptide serum directed
      against the preS2 domain was reactive with WHV envelope proteins, recognizing the
      preS2 and preS1 proteins by their preS2 epitopes. With recombinant fusion
      proteins we generated several anti-S sera, which recognized all envelope
      proteins, and anti-preS2 antisera, which recognized the preS proteins. Results
      obtained with our antisera showed that sera of infected woodchucks lack the low
      glycosylated form (GP33) of the preS2 protein, unlike human hepatitis B virus.

PMID- 1993878
TI  - Natural and experimental infection of wild mallard ducks with duck hepatitis B
      virus.
AB  - Wild duck populations were investigated over a 4 year period for duck hepatitis B
      virus (DHBV) infection and liver disease. It appeared that DHBV is endemic in
      wild migratory mallards from France and the U.S.A., although neither
      hepatocellular carcinoma nor viral DNA integration could be detected in liver
      samples examined. The follow up of natural infection indicated that wild mallards
      developed significantly higher serum titres to DHBV DNA than Pekin ducks. The
      results of experimental transmission demonstrated that such differences in
      viraemia were not related to the breed of ducks but to the virus isolate, since
      the wild mallard-isolated DHBV (DHBV WM) induced significantly higher viraemia in
      both mallard and Pekin ducklings compared to the domestic Pekin DHBV (DHBVP)
      isolate. The naturally infected mallard and Pekin ducks had only minor
      histological lesions of the liver compared with experimentally infected birds.
      There was no correlation between the intensity of viraemia and the severity of
      liver lesions, suggesting that as for mammalian hepadnaviruses the hepatic injury
      in DHBV-infected ducks is probably immunologically mediated.

PMID- 1993880
TI  - Formation in vitro of the pTP-dCMP initiation complex of human adenovirus type
      12.
AB  - We report the covalent addition of [32P]dCMP to a protein from group A adenovirus
      12 (Ad12)-infected human (KB) cells in vitro, using crude extracts. Synthesis of
      the 60K protein-dCMP complex required a DNA template containing a terminally
      located adenovirus replication origin; the protein-dCMP bond was alkali-labile
      but acid-stable. We therefore conclude that this product is the Ad12 terminal
      protein precursor (pTP)-dCMP initiation complex for DNA replication. Synthesis of
      Ad12 pTP-dCMP was specific for dCTP but was stimulated by dATP. In contrast to
      Ad2, the Ad12 initiation reaction required ATP. Antipeptide antiserum targeted to
      Ad DNA polymerase inhibited Ad12 pTP-dCMP synthesis in vitro, providing evidence
      that Ad DNA polymerase catalyse dCMP addition to pTP during initiation.

PMID- 1993881
TI  - Comparison of the nucleotide sequence of the SH gene and flanking regions of
      mumps vaccine virus (Urabe strain) grown on different substrates and isolated
      from vaccinees.
AB  - The small hydrophobic (SH) protein gene and flanking regions of the Urabe Am9
      vaccine strain of mumps virus were amplified by the polymerase chain reaction and
      sequenced directly by the dideoxynucleotide chain termination method. The 434 bp
      sequence was identical for the Urabe strain isolated from vaccines produced by
      three manufacturers and for virus isolated following post-vaccination parotitis.
      No changes were detected for coding, non-coding or intergenic regions between
      virus grown on different substrates. The Urabe virus SH coding region differed
      from the published sequence for strain SBL-1 by 14.4% at the nucleotide level and
      24.6% at the amino acid level. The 5' non-coding SH region was strongly conserved
      between the two strains (2% different), whereas the other non-coding regions were
      not.

PMID- 1993882
TI  - Measles virus: both the haemagglutinin and fusion glycoproteins are required for
      fusion.
AB  - Vaccinia-measles recombinant viruses were used to examine the contribution of the
      individual measles virus glycoproteins in fusion. Although vaccinia virus
      recombinants expressing either the haemagglutinin or fusion proteins did not
      induce fusion in the cell lines examined, a double recombinant expressing both
      measles virus glycoproteins gave extensive syncytia in cells of human and simian
      origin. No fusion was observed in mouse, hamster or chicken cells. The fusion
      induced by the double recombinant could be specifically inhibited with either
      anti-fusion or anti-haemagglutinin monoclonal antibodies.

PMID- 1993883
TI  - The nucleotide sequence of the gene encoding the attachment protein H of canine
      distemper virus.
AB  - The sequence of the H gene and flanking sequences in the F and L genes of canine
      distemper virus (CDV) have been determined. The H gene of CDV (1946 nucleotides)
      contains one large open reading frame starting at position 21 and terminating at
      position 1835, encoding a protein of 604 amino acid residues. This protein
      contains three potential glycosylation sites in the extracellular domain and,
      like all other paramyxoviruses, a N-terminal membrane-spanning hydrophobic anchor
      domain. The deduced H protein sequence shows an identity of 36% with rinderpest
      virus (RPV) and measles virus (MV). The identities at the nucleotide level are
      higher (RPV 52% and MV 53%). The amino acid sequence shows conservation of all
      the structural determinants with the H proteins of MV and RPV. The data also show
      that CDV is evolutionarily equidistant to RPV and MV with respect to the H gene.

PMID- 1993884
TI  - Cloning and sequencing of the S RNA from a Bulgarian isolate of tomato spotted
      wilt virus.
AB  - Libraries of cloned cDNA were prepared from complete genomic RNA and isolated S
      RNA of the Bulgarian L3 isolate of tomato spotted wilt virus (TSWV-L3). Northern
      blotting of TSWV genomic RNA detected clones specific for the L, M and S RNAs in
      the library from complete RNA. S RNA-specific clones selected from both libraries
      covered approximately 2.8 kb (about 95%) of the S RNA. Sequencing of these clones
      showed TSWV-L3 S RNA to be ambisense. It contains two open reading frames (ORFs);
      one of 1401 nucleotides located on the viral RNA encodes an Mr 52,400 (52K)
      protein, and the other of 774 nucleotides on the complementary strand encodes an
      Mr 28,900 (29K) protein. Expression of the 29K ORF in bacteria and immunological
      analysis of the fusion protein synthesized confirmed that the 29K protein is the
      N protein of TSWV-L3. Comparison with the published sequence for the S RNA of a
      Brazilian TSWV isolate, CNPH1, revealed almost complete identity in the amino
      acid sequences for the 29K protein, but several clustered amino acid exchanges in
      the putative 52K protein. In addition, the separating non-translated intergenic
      region of the S RNA of the Bulgarian isolate is 81 nucleotides longer than that
      of CNPH1.

PMID- 1993885
TI  - Ambisense segment 3 of rice stripe virus: the first instance of a virus
      containing two ambisense segments.
AB  - The complete nucleotide sequence of rice stripe virus (RSV) segment 3 shows that
      it has two open reading frames, one in the viral-complementary sequence, which
      codes for the nucleocapsid protein, and the other in the viral-sense sequence.
      The non-coding region between the ambisense genes in RSV segment 3 contains
      several U and A tracts, as do the ambisense S segments of phleboviruses and
      uukuviruses. As we have previously shown that RSV segment 4 has an ambisense
      nature, this is the first instance of a virus containing two ambisense segments.

PMID- 1993886
TI  - Nucleotide sequence of raspberry bushy dwarf virus RNA-3.
AB  - A nucleotide sequence is reported for RNA-3, the smallest of the three major RNA
      species found in particles of raspberry bushy dwaft virus (RBDV). The sequence of
      946 nucleotides contains a single large open reading frame which encodes an Mr
      30,509 polypeptide. In vitro translation of RNA-3 yielded an Mr 30,000 product
      that reacted specifically with antiserum to RBDV particles and we conclude that
      the amino acid sequence deduced from the sequence of RNA-3 is that of the RBDV
      coat protein, or an immediate precursor of it. No affinities were detected by
      comparing the nucleotide sequence of RNA-3 with the sequences of other plant
      viruses.

PMID- 1993887
TI  - Single-step purification and biological activity of human nerve growth factor
      produced from insect cells.
AB  - Human nerve growth factor (NGF) was cloned and engineered for expression in a
      baculovirus-infected Spodoptera frugiperda (SF-9) insect cell system. Culture
      supernatants contained 2-3 mg/L of recombinant human NGF. The human NGF produced
      by this system was purified to apparent homogeneity with a single-step affinity
      chromatography procedure using a high-affinity monoclonal antibody originally
      raised against murine NGF. The purification procedure yielded 1-2 mg of pure,
      human NGF per liter of culture supernatant; i.e., approximately 60% recovery of
      the human NGF originally released into the culture medium. Although the gene
      transfected into the SF-9 cells coded for pro-NGF, the NGF recovered after
      purification was greater than 95% fully processed, mature protein. The KD for the
      affinity of the pure, recombinant human NGF for NGF receptor in PC12 membranes is
      0.20 +/- 0.05 nM. Activation of neurite outgrowth in PC12 cells occurs with ED50
      values of 85 +/- 20 pM and 9.6 +/- 1.5 pM for a 3-day primary response and a 1
      day secondary response, respectively. The pure, recombinant human NGF also
      stimulates a significant increase in dopamine content of PC12 cells with an ED50
      of 5.8 +/- 2.7 pM. These binding and biological activation properties are
      consistent with values observed using murine NGF purified from submaxillary
      glands.

PMID- 1993888
TI  - Cell cycling of astrocytes and their precursors in primary cultures: a mevalonate
      requirement identified in late G1, but before the G1/S transition, involves
      polypeptides.
AB  - The relationship between mevalonate and cell cycling was investigated in
      developing glial cells. Primary cultures of newborn rat brains were serum
      depleted (0.1%, vol/vol) for 48 h on days 4-6 in vitro, then returned to 10% calf
      serum (time 0). After 48 h, 70-80% of the cells were glial fibrillary acidic
      protein (GFAP)-negative by indirect immunofluorescence; 79 +/- 7% were GFAP
      positive after an additional 3 days. Serum shift-up resulted in 12 h of
      quiescence, and then by 20 h (S phase) in increased proportions of cells
      synthesizing DNA (from 15 +/- 6% to 75 +/- 4% by bromodeoxyuridine
      immunofluorescence at 12 h and 20 h, respectively) and rates of DNA synthesis (42
      +/- 6 versus 380 +/- 32 cpm/micrograms of protein/h of [3H]thymidine uptake).
      Additional mevalonate (25 mM) for 30 min at 10 h reversed the inhibition of DNA
      synthesis apparent with mevinolin (150 microM), an inhibitor of mevalonate
      synthesis, present from time 0. Cycloheximide added simultaneously with
      mevalonate prevented this reversal of inhibition. To cause arrest at G1/S,
      cultures were exposed to hydroxyurea between 10 and 22 h. By 3 h after
      hydroxyurea removal, bromodeoxyuridine-labeled nuclei increased from 0% to 75 +/-
      9%, and DNA synthesis increased 10-fold. Mevinolin failed to inhibit these
      increases. Thus, primary astroglial precursors stimulated to progress through the
      cell cycle express a mevalonate requirement in late G1, but before the G1/S
      transition. The effect of mevalonate was characterized further as being brief (30
      min) and as requiring polypeptides.

PMID- 1993890
TI  - Immunoreactive basic fibroblast growth factor-like proteins in chromaffin
      granules.

PMID- 1993889
TI  - Changes in inositol 1,4,5-trisphosphate and inositol 1,3,4,5- tetrakisphosphate
      mass accumulations in cultured adrenal chromaffin cells in response to bradykinin
      and histamine.
AB  - In previous studies it has been shown that both bradykinin and histamine increase
      the formation of 3H-labeled inositol phosphates in adrenal chromaffin cells
      prelabelled with [3H]inositol and that both these agonists stimulate release of
      catecholamines by a mechanism dependent on extracellular calcium. Here, we have
      used mass assays of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] and inositol
      1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P4] to investigate changes in levels of
      these two candidates as second messengers in response to stimulation with
      bradykinin and histamine. Bradykinin increased the mass of Ins(1,3,4,5)P4 despite
      the failure in earlier studies with [3H]inositol-labelled cells to observe a
      bradykinin-mediated increase in content of [3H]InsP4. Bradykinin elicited a very
      rapid increase in level of Ins(1,4,5)P3, which was maximal at 5-10 s and then
      rapidly decreased to a small but sustained elevation at 2 min. The bradykinin
      elicited Ins(1,3,4,5)P4 response increased to a maximum at 30-60 s and at 2 min
      was still elevated severalfold above basal levels. Histamine, which produced a
      larger overall total inositol phosphate response in [3H]inositol-loaded cells,
      produced significantly smaller Ins(1,4,5)P3 and Ins(1,3,4,5)P4 responses compared
      with bradykinin. The bradykinin stimulation of Ins(1,4,5)P3 accumulation was
      partially dependent on a high (1.8 mM) extracellular Ca2+ concentration, whereas
      the Ins(1,3,4,5)P4 response was almost completely lost when the extracellular
      Ca2+ concentration was reduced to 100 nM. Changes in the inositol polyphosphate
      second messengers are compared with the time course of bradykinin-stimulated
      increases in free intracellular Ca2+ concentrations and noradrenaline release.

PMID- 1993891
TI  - Stereotaxic injection of tetanus toxin in rat central nervous system causes
      alteration in normal levels of monoamines.
AB  - A single intraventricular injection of tetanus toxin produced a time-dependent
      elevation of serotonin levels in brain and spinal cord of adult rats. This
      tetanus toxin-induced increase was produced in areas of high density of
      serotonergic innervation, such as the hypothalamus, hippocampus, and spinal cord.
      Little or no effect was found in the thalamus, cerebellum, and frontal cortex,
      areas that are poorly innervated by serotonergic terminals. The responses of
      catecholamines (no change in dopamine level and generalized decrease in
      norepinephrine) pointed to a specific action of tetanus toxin on the serotonergic
      system. Stereotaxic injections of tetanus toxin in dorsal or magnus raphe nuclei
      did not have an evident effect on biogenic amine levels in the brain and spinal
      cord, respectively. Because direct stereotaxic injections of the toxin in the
      hypothalamus or hippocampus produced significant serotonin increases in both
      areas, it is proposed that tetanus toxin interacts with presynaptic targets to
      produce serotonin accumulation; this is probably due in part to an activation of
      tryptophan 5-hydroxylase.

PMID- 1993892
TI  - The anxiogenic beta-carboline FG 7142 selectively increases dopamine release in
      rat prefrontal cortex as measured by microdialysis.
AB  - The effect of the anxiogenic beta-carboline methyl-beta-carboline-3-carboxyamide
      (FG 7142) on dopamine release in prefrontal cortex and striatum in the awake
      freely moving rat was determined using the technique of microdialysis. FG 7142
      (25 mg/kg, i.p.) caused a time-dependent increase in dopamine release in
      prefrontal cortex which was statistically significantly greater than the response
      to vehicle administration. Dopamine release in striatum was unaltered by FG 7142.
      Pretreatment of animals with the benzodiazepine antagonist Ro 15-1788 (30 mg/kg,
      i.p., 15 min prior to FG 7142 administration) completely abolished the increase
      in dopamine release caused by FG 7142 in prefrontal cortex. These data indicate
      that the anxiogenic benzodiazepine inverse agonist FG 7142 can selectively
      increase dopamine release in prefrontal cortex, and that this effect appears to
      be mediated via the gamma-aminobutyric acid/benzodiazepine receptor complex.

PMID- 1993893
TI  - Identification of meningeal cell released neurite promoting activities for
      embryonic hippocampal neurons.
AB  - Primary cultures of meningeal cells from embryonic rat cerebra secrete neurite
      growth-inducing components into serum-free culture medium. This conditioned
      medium (CM) was analyzed by FPLC and immunochemical and enzymatic treatments and
      tested for neurite promoting activity (NPA) in a quantitative bioassay using
      hippocampal neurons from embryonic rat. By immunoprecipitation or specific
      adsorption we identified laminin (LN)-proteoglycan complexes and fibronectin
      (FN), respectively, as the major neurite promoting components within meningeal
      cell CM. The LN-proteoglycan complexes and their NPA were sensitive to
      chondroitinase (chondroitin ABC lyase, EC 4.2.2.4) and to a smaller extent to
      heparitinase (heparitin sulfate lyase, EC 4.2.2.8). Minor fractions of the total
      NPA in CM correlated with free LN and a putative but not yet characterized FN
      proteoglycan complex.

PMID- 1993894
TI  - [14C]leucine incorporation into brain proteins in gerbils after transient
      ischemia: relationship to selective vulnerability of hippocampus.
AB  - Regional [14C]leucine incorporation into brain proteins was studied in gerbils
      after global ischemia for 5 min and recirculation times of 45 min to 7 days,
      using a combination of quantitative autoradiography and biochemical analysis.
      After recirculation for 45 min, incorporated radioactivity was reduced to
      approximately 20-40% of control values in all ischemic brain regions. Specific
      activity of the tracer, in contrast, was increased, a finding indicating that the
      reduced incorporation of radioactivity was not due to reduced tracer influx from
      plasma or a dilution of the tracer by increased proteolysis. After recirculation
      for 6 h, [14C]leucine incorporation returned to control levels in all regions
      except the CA1 sector of the hippocampus, where it amounted to less than 50%.
      After 1 day, protein synthesis in the CA1 sector returned to approximately 70% of
      control values, followed by a secondary decline to less than 50% after 3 days and
      returned to near control values after 7 days. Histological evaluations revealed
      selective neuronal death in the CA1 sector of the hippocampus after 3 days of
      recirculation. The complex time course of protein synthesis in the CA1 sector
      suggests a biphasic mode of injury, which may be related to similar changes of
      calcium homeostasis. The final return to near normal after CA1 neurons have
      disappeared is explained by astroglial proliferation and demonstrates that at
      this time protein synthesis is not a marker of neuronal viability.

PMID- 1993895
TI  - Isolation and sequence of partial cDNA clones of human L1: homology of human and
      rodent L1 in the cytoplasmic region.
AB  - We have isolated cDNA clones coding for the human homologue of the neuronal cell
      adhesion molecule L1. The nucleotide sequence of the cDNA clones and the deduced
      primary amino acid sequence of the carboxy terminal portion of the human L1 are
      homologous to the corresponding sequences of mouse L1 and rat NILE glycoprotein,
      with an especially high sequences identity in the cytoplasmic regions of the
      proteins. There is also protein sequence homology with the cytoplasmic region of
      the Drosophila cell adhesion molecule, neuroglian. The conservation of the
      cytoplasmic domain argues for an important functional role for this portion of
      the molecule.

PMID- 1993896
TI  - Gene expression in different cell types of aging rat brain.
AB  - "Bound" and "free" RNA polymerase activities were assessed in the nuclear
      fraction of cerebral cortical, neuronal, astroglial, and oligodendroglial cells
      obtained from rats of young, adult, and old ages. Significant decreases in both
      the bound and free polymerase II activities were noticed in old brain, as
      compared to adult brain, in neuronal and oligodendroglial nuclei. In astroglia,
      only the free polymerase II was found to be affected. No effect of aging could be
      seen on the activity of bound RNA polymerase I + III. The free RNA polymerase I +
      III activity was increased from adult to old age in neuronal nuclei, but
      unchanged in oligodendroglial and astroglial nuclei. The age-dependent reduction
      in RNA polymerase II was maximum in oligodendroglial cells, whereas it was least,
      although still significant, in neuronal cells. DNA isolated from old brain was
      unable to enhance the transcriptional activity when added to chromatin
      preparations obtained from rat brains of any of the above ages and the "old"
      chromatin was unable to accept even the "young" DNA as additional exogenous
      template. It is concluded that the reduced gene expression noticed in old brain
      nuclei is due to both altered chromatin/DNA structure and inadequate levels of
      free RNA polymerase II.

PMID- 1993897
TI  - Multiple proteases regulate neurite outgrowth in NB2a/dl neuroblastoma cells.
AB  - Mouse NB2a/dl neuroblastoma cells elaborate axonal neurites in response to
      various chemical treatments including dibutyryl cyclic AMP and serum deprivation.
      Hirudin, a specific inhibitor of thrombin, initiated neurite outgrowth in NB2a/dl
      cells cultured in the presence of serum; however, these neurites typically
      retracted within 24 h. The cysteine protease inhibitors leupeptin and N-acetyl
      leucyl-leucyl-norleucinal (CI; preferential inhibitor of micromolar calpain but
      also inhibits millimolar calpain) at 10(-6) M considerably enhanced neurite
      outgrowth induced by serum deprivation, but could not induce neuritogenesis in
      the presence of serum. A third cysteine protease inhibitor, N-acetyl-leucyl
      leucyl-methional (CII; preferential inhibitor of millimolar calpain but also
      inhibits micromolar calpain), had no detectable effects by itself. Cells treated
      simultaneously with hirudin and either leupeptin, CI, or CII elaborated stable
      neurites in the presence of serum. Cell-free enzyme assays demonstrated that
      hirudin inhibited thrombin but not calpain, CI and CII inhibited calpain but not
      thrombin, and leupeptin inhibited both proteases. These results imply that
      distinct proteolytic events, possibly involving more than one protease, regulate
      the initiation and subsequent elongation and stabilization of axonal neurites.
      Since the addition of exogenous thrombin or calpain to serum-free medium did not
      modify neurite outgrowth, the proteolytic events affected by these inhibitors may
      be intracellular or involve proteases distinct from thrombin or calpain.

PMID- 1993899
TI  - Regulation of proenkephalin synthesis in adrenal medullary chromaffin cells.
AB  - The synthesis of proenkephalin was assessed in primary cultures of bovine adrenal
      medullary chromaffin cells by incubation of the cells with [35S]methionine,
      digestion of proenkephalin-derived peptides with trypsin and carboxy-peptidase B,
      and quantitation of radioactivity incorporated into Met-enkephalin following
      reversed-phase HPLC. Nicotine, histamine, and vasoactive intestinal peptide each
      enhanced the rate of proenkephalin synthesis approximately 10-fold when examined
      between 16 and 32 h after the drug or hormone addition. Inclusion of nifedipine
      (1 microM) partially blocked the stimulatory effect of nicotine, but not that of
      vasoactive intestinal peptide or histamine, or proenkephalin synthesis.
      Theophylline, tetrabenazine, and angiotensin II also increased the rate of
      proenkephalin synthesis (three- to eight-fold). These increases in the apparent
      rate of proenkephalin synthesis were not attributable to altered [35S]methionine
      specific radioactivity or rates of turnover and did not reflect similar increases
      in total protein synthesis. The half-life for turnover of Met-enkephalin
      sequences was 3-4 days in the cultured chromaffin cell. These studies directly
      show that proenkephalin synthesis is the primary regulatory step in control of
      chromaffin cell opioid peptide content.

PMID- 1993898
TI  - Cholecystokinin modulates the release of dopamine from the anterior and posterior
      nucleus accumbens by two different mechanisms.
AB  - The effects of various cholecystokinin (CCK)-related peptides were investigated
      on 35 mM K(+)-stimulated endogenous dopamine release from slices of either
      anterior or posterior nucleus accumbens of the rat. CCK sulphated octapeptide (1
      10 microM), but not pentagastrin or CCK unsulphated octapeptide, was found to
      cause a dose-dependent increase in the release from the posterior nucleus
      accumbens. This effect was blocked by low doses of the CCKA receptor antagonist
      L364,718 (10 nM) but not the CCKB receptor antagonist L365,260. In the anterior
      nucleus accumbens CCK sulphated octapeptide (1 microM) and CCK unsulphated
      octapeptide (0.1-1 microM) inhibited the dopamine release, and this effect was
      blocked by L365,260 (10-100 nM) but not by L364,718. These results suggest that
      CCK has a different effect on dopamine release from the anterior and posterior
      nucleus accumbens and that these effects are mediated by two different types of
      CCK receptor.

PMID- 1993900
TI  - A comparison of axonal and somatodendritic dopamine release using in vivo
      dialysis.
AB  - The release of endogenous dopamine from the axon terminal field in the nucleus
      accumbens and from the A10 dopamine cell bodies of conscious rats was measured
      using intracranial dialysis. Release of dopamine from both areas was calcium
      dependent and markedly inhibited by the presence of the D2 agonist, quinpirole,
      in the dialysis buffer. However, the addition of tetrodotoxin to the buffer
      produced less of a decrease in dopamine in the A10 region than in the nucleus
      accumbens. When dopamine release was examined by substituting K+ for Na+ or by
      adding amphetamine to the buffer, the evoked release was significantly less in
      the A10 region than in the nucleus accumbens. Likewise, enhanced extracellular
      dopamine following blockade of reuptake by nomifensine addition to the dialysis
      buffer was not as great in the A10 region as in the nucleus accumbens. These data
      argue that, in general, axonal and somatodendritic dopamine release are regulated
      by similar factors, although somatodendritic release is less influenced by action
      potential generation and less responsive to some releasing agents.

PMID- 1993901
TI  - Hydromyelic hydrocephalus. Correlation of hydromyelia with various stages of
      hydrocephalus in postshunt isolated compartments.
AB  - The clinical features and pathophysiology of specific forms of hydromyelia are
      analyzed in this report together with the chronological changes of associated
      hydrocephalus. Nine patients were studied; all had hydromyelia with varying
      degrees of associated hydrocephalus. Clinically applicable classification systems
      were used to evaluate the progression of hydrocephalus (Stages I to IV) and to
      define the compartment isolated after shunting in the previously communicating
      cerebral ventricles (Types I to IV). Four patients had Stage IV disease
      (holoneural canal dilatation); one had Stage II and four had Stage I disease
      (both Stages I and II with supratentorial hydrocephalus). All patients were
      initially treated by ventriculoperitoneal shunting at an average age of 9.9
      years. Five patients had progressive spinal symptoms before or after treatment of
      their hydrocephalus. Two patients had Type III isolation (an isolated
      rhombencephalic ventricle) with a functioning ventricular shunt; ventriculography
      confirmed a communication between the fourth ventricle and the hydromyelia, and
      both patients improved after placement of a shunt in the fourth ventricle. The
      remaining patients had Type IV isolation (isolated central canal dilatation) with
      a functioning ventricular shunt. This study indicates that in some cases the
      pathophysiology of hydromyelia is closely related to associated hydrocephalus. A
      new concept of the development of an isolated compartment after shunting is
      proposed to explain the progression of hydromyelia in these cases.

PMID- 1993902
TI  - Functional outcomes following selective posterior rhizotomy in children with
      cerebral palsy.
AB  - The recent increase in popularity of selective posterior rhizotomy demands
      objective documentation of surgical outcome. For this reason, the authors have
      analyzed the status of 25 children with spastic cerebral palsy before and after
      rhizotomy to determine the effects of this therapy on muscle tone, range of
      movement, and motor function. Postoperative tests showed a reduction in muscle
      tone compared with preoperative assessments. Range of motion in the lower
      extremities was significantly increased and improvements in functional gross
      motor skills were noted. An increase in range of motion in the knees and thighs
      during gait was detected in 18 ambulatory patients studied with computerized two
      dimensional motion analysis. Preliminary findings indicate that selective
      posterior rhizotomy reduced spasticity, thereby increasing range of motion and
      contributing to improvements in active functional mobility.

PMID- 1993903
TI  - Platelet thromboxane release and delayed cerebral ischemia in patients with
      subarachnoid hemorrhage.
AB  - Adenosine diphosphate-induced platelet aggregation and associated thromboxane B2
      release were studied in 52 patients with subarachnoid hemorrhage (SAH) in order
      to detect a possible association between altered platelet function and
      development of cerebral ischemic complications after SAH. Compared to the values
      on admission, the patients showed significantly increased platelet aggregability
      (p less than 0.05) and thromboxane release (p less than 0.001) 1 to 2 weeks after
      SAH. The highest values of thromboxane release were seen in patients who
      deteriorated due to delayed cerebral ischemia with a permanent neurological
      deficit. Thromboxane release was significantly higher (p less than 0.05) before
      the onset of severe delayed ischemia in six patients with preoperative ischemia
      compared to the patients without delayed ischemia. In five others, both ischemic
      deterioration and elevated thromboxane release occurred after operation. These
      patients had preoperative values similar to the values in those without ischemic
      symptoms. The observations suggest that increased platelet aggregability and
      thromboxane release are associated with delayed cerebral ischemia both before and
      after surgery.

PMID- 1993904
TI  - Endovascular occlusion of vertebral arteries in the treatment of unclippable
      vertebrobasilar aneurysms.
AB  - Twenty-one patients with aneurysms of the vertebrobasilar circulation underwent
      unilateral or bilateral endovascular occlusion of the vertebral artery. Six
      patients presented with subarachnoid hemorrhage (SAH), 10 with mass effect, four
      with mass effect and SAH, and one with ischemic symptoms. Thirteen patients had
      good outcomes with complete clinical and angiographic cure. Six patients had
      partial thrombosis of their aneurysms. There was one death and one treatment
      failure. One patient suffered transient stroke. It is concluded that endovascular
      occlusion of the vertebral artery following test occlusion is a safe and
      effective treatment for proximal aneurysms of the vertebrobasilar circulation.

PMID- 1993906
TI  - Spontaneous neuronal hyperactivity in the medial and intralaminar thalamic nuclei
      of patients with deafferentation pain.
AB  - Electrical activity was recorded from single cells in the thalamus of 10 patients
      with chronic pain associated with deafferentation. Under local anesthesia, these
      patients underwent either electrode implantation or thalamotomy for treatment of
      their pain. In eight of the 10 patients, single units were identified as
      discharging spontaneously in high-frequency, often rhythmic, bursts. The
      discharges were of two types: short bursts comprised of two to six spikes with a
      burst frequency of one to four per second; and long trains of 30 to 80 spikes of
      similar frequency. Reconstruction of electrode trajectories indicated that
      recordings were made from the region corresponding to the lateral aspect of the
      mediodorsal thalamic nucleus, the central lateral nucleus, a small part of the
      central median nucleus, and the parafascicular nucleus. In the eight patients in
      whom spontaneous neuronal burst activity was exhibited, it was impossible to
      study activity evoked by natural cutaneous stimulation due to the continuous
      spontaneous neuronal discharges. Both animal and human studies have suggested
      that pain related to deafferentation is accompanied by spontaneous hyperactivity
      in the dorsal horn of the spinal cord and in the ventral posterior thalamic
      nuclei. The authors present evidence of spontaneous neuronal hyperactivity in the
      intralaminar thalamic nuclei of patients with pain related to deafferentation.
      The findings suggest that spontaneous neuronal discharge in patients with pain
      related to deafferentation is more widespread in the central nervous system than
      has been previously appreciated. The results have important implications for the
      surgical treatment of chronic pain.

PMID- 1993905
TI  - Gemistocytic astrocytomas: a reappraisal.
AB  - Although gemistocytic astrocytomas are considered slow-growing astrocytomas, they
      often behave aggressively. To clarify the biological and clinical behavior of
      these rare tumors, the authors retrospectively identified 59 patients with
      gemistocytic astrocytoma whose tumors were diagnosed and treated between June,
      1976, and July, 1989. Three patients who were lost to follow-up review were
      excluded, as were two whose original slides could not be obtained and three whose
      tumors were diagnosed at recurrence or at autopsy. The pathological material of
      the remaining 51 patients was reviewed using two sets of histological criteria.
      Thirteen patients (Group A) had "pure" gemistocytic astrocytoma, defined as a
      glial tumor with more than 60% gemistocytes/high-power field and a background of
      fibrillary astrocytes. Fifteen patients (Group B) had "mixed" gemistocytic
      astrocytoma, defined as a glial tumor with 20% to 60% gemistocytes/high-power
      field and a background of anaplastic astrocytes. Twenty-three tumors did not meet
      these criteria and were excluded from analysis. The median age of the patients
      was 48.5 years in Group A and 38.3 years in Group B (p less than 0.05). In both
      groups, the median Karnofsky Performance Scale score was greater than 90%. All
      patients underwent surgical procedures (four total and 19 partial resections, and
      five biopsies) and postoperative radiation therapy. The majority also had
      interstitial brachytherapy, chemotherapy, or both. Ten patients had one
      reoperation for tumor recurrence and one had two reoperations; other treatments
      for recurrence included brachytherapy, chemotherapy, and repeat irradiation. All
      four patients who originally underwent gross total resection are still alive; all
      five who had a biopsy have died. There was no significant difference in median
      survival times between groups: 136.5 weeks in Group A (range 10 to 310+ weeks)
      and 135.6 weeks in Group B (range 31 to 460+ weeks). Analysis of all 28 patients
      showed a better prognosis for patients less than 50 years of age (185 vs. 36
      weeks survival time; p less than 0.001), patients with preoperative symptoms
      lasting for more than 6 months (228.1 vs. 110.2 weeks survival time; p less than
      0.05), and patients with seizures as the first symptom (185.7 vs. 80 weeks
      survival time; p less than 0.01). Survival time did not correlate with the
      presence of perivascular lymphocytic infiltration. The authors conclude that the
      presence of at least 20% gemistocytes in a glial neoplasm is a poor prognostic
      sign, irrespective of the pathological background. It is proposed that
      gemistocytic astrocytomas be classified with anaplastic astrocytomas and treated
      accordingly.

PMID- 1993907
TI  - Radical intracapsular removal of acoustic neurinomas. Long-term follow-up review
      of 11 patients.
AB  - Historically, the neurosurgical treatment of large acoustic neurinomas has
      developed with two principal goals: complete tumor removal and preservation of
      facial nerve function. A recent goal for small tumors is the preservation of
      hearing. Out of a personal series of 124 acoustic neurinomas treated over the
      past 35 years, the senior author has undertaken a radical intracapsular approach
      in 12 patients with large tumors (greater than 3 cm in diameter). Surgical
      indications for intracapsular removal included advanced age (five cases), the
      patient's wish to avoid any risk of facial paralysis (six cases), contralateral
      facial palsy (one case), and contralateral deafness (one case). Eleven of these
      12 patients were available for follow-up review. Tumor recurrence developed in
      two patients (18%) at 2 and 3 years postoperatively; there were no late
      recurrences. Four patients died of unrelated causes, 10 to 19 years after
      surgery. The remaining five patients have survived a mean of 12 years since
      surgery without recurrence (range 3 to 22 years). Facial function was preserved
      in nine patients (82%). The results suggest that radical intracapsular removal
      may be the procedure of choice under certain circumstances and may offer an
      alternative to focused high-energy radiation.

PMID- 1993908
TI  - Radiation-induced optic neuropathy: a magnetic resonance imaging study.
AB  - Optic neuropathy induced by radiation is an infrequent cause of delayed visual
      loss that may at times be difficult to differentiate from compression of the
      visual pathways by recurrent neoplasm. The authors describe six patients with
      this disorder who experienced loss of vision 6 to 36 months after neurological
      surgery and radiation therapy. Of the six patients in the series, two had a
      pituitary adenoma and one each had a metastatic melanoma, multiple myeloma,
      craniopharyngioma, and lymphoepithelioma. Visual acuity in the affected eyes
      ranged from 20/25 to no light perception. Magnetic resonance (MR) imaging showed
      sellar and parasellar recurrence of both pituitary adenomas, but the intrinsic
      lesions of the optic nerves and optic chiasm induced by radiation were enhanced
      after gadolinium-diethylenetriaminepenta-acetic acid (DTPA) administration and
      were clearly distinguishable from the suprasellar compression of tumor. Repeated
      MR imaging showed spontaneous resolution of gadolinium-DTPA enhancement of the
      optic nerve in a patient who was initially suspected of harboring recurrence of a
      metastatic malignant melanoma as the cause of visual loss. The authors found the
      presumptive diagnosis of radiation-induced optic neuropathy facilitated by MR
      imaging with gadolinium-DTPA. This neuro-imaging procedure may help avert
      exploratory surgery in some patients with recurrent neoplasm in whom the etiology
      of visual loss is uncertain.

PMID- 1993909
TI  - Interstitial chemotherapy with drug polymer implants for the treatment of
      recurrent gliomas.
AB  - Malignant gliomas have been difficult to treat with chemotherapy. The most
      effective agent, BCNU (carmustine), has considerable systemic toxicity and a
      short half-life in serum. To obviate these problems, a method has been developed
      for the local sustained release of chemotherapeutic agents by their incorporation
      into biodegradable polymers. Implantation of the drug-impregnated polymer at the
      tumor site allows prolonged local exposure with minimal systemic exposure. In
      this Phase I-II study, 21 patients with recurrent malignant glioma were treated
      with BCNU released interstitially by means of a polyanhydride biodegradable
      polymer implant. Up to eight polymer wafers were placed in the resection cavity
      intraoperatively, upon completion of tumor debulking. The polymer releases the
      therapeutic drug for approximately 3 weeks. Three increasing concentrations of
      BCNU were studied; the treatment was well tolerated at all three levels. There
      were no adverse reactions to the BCNU wafer treatment itself. The average
      survival period after reoperation was 65 weeks for the first dose group, 64 weeks
      for the second dose group, and 32 weeks for the highest dose group. The overall
      mean survival time was 48 weeks from reoperation and 94 weeks from the original
      operation. The overall median survival times were 46 weeks postimplant and 87
      weeks from initial surgery. Eighteen (86%) of 21 patients lived more than 1 year
      from the time of their initial diagnosis and eight (38%) of 21 patients lived
      more than 1 year after intracranial implantation of the polymer. Frequent
      hematology, blood chemistry, and urinalysis tests did not reveal any systemic
      effect from this interstitial chemotherapy. Since the therapy is well tolerated
      and safe, a placebo-controlled clinical trial has been started. The trial will
      measure the effect of the second treatment dose on survival of patients with
      recurrent malignant glioma.

PMID- 1993910
TI  - Characterization of astrocytomas, meningiomas, and pituitary adenomas by
      phosphorus magnetic resonance spectroscopy.
AB  - Phosphorus magnetic resonance (MR) spectroscopy allows noninvasive measurement of
      phosphate-containing compounds and pH within brain cells. The authors obtained
      localized phosphorus MR spectra from 10 normal brains, four low-grade
      astrocytomas, six glioblastomas, four meningiomas, and three pituitary adenomas
      and found differences in the spectra of each tumor type. Compared to normal
      brain, the spectra from low-grade astrocytomas showed a significant reduction of
      the phosphodiester (PDE) peak. Glioblastomas were characterized by a significant
      reduction of the PDE peak, elevation of the phosphomonoester (PME) peak, and a
      relatively alkaline intracellular pH. The spectra from meningiomas and pituitary
      adenomas were markedly different from the glial tumors. Meningiomas showed
      significant reductions in phosphocreatine, PDE, and inorganic phosphate, as well
      as a relatively alkaline pH. Pituitary adenomas resembled meningiomas, but had a
      much higher PME peak. Although the number of tumors studied was small, there
      appears to be a characteristic spectrum associated with these different tumor
      types. The present findings can be useful in the preoperative identification of
      these tumors and in furthering understanding of their growth and metabolism in
      vivo.

PMID- 1993911
TI  - Effect of 21-aminosteroid U-74006F on lipid peroxidation in subarachnoid clot.
AB  - The present study was undertaken to investigate the effect of U-74006F on
      malondialdehyde (a by-product of lipid peroxidation) in subarachnoid clot.
      Eighteen cynomolgus monkeys were divided into three groups of six each. There
      were two U-74006F-treated groups, receiving doses of 0.3 or 1.0 mg/kg, and a
      placebo-treated group. Each monkey underwent baseline cerebral angiography
      followed by right-sided craniectomy and placement of subarachnoid clot around the
      middle cerebral artery (MCA). Treatment was administered intravenously every 8
      hours for 6 days. Seven days after the experimental subarachnoid hemorrhage
      (SAH), angiography was repeated and the animals were killed. In the placebo
      treated group, significant vasospasm occurred in the MCA on the side of the clot
      (p less than 0.01). After U-74006F treatment at both dosages, significantly less
      vasospasm developed in the clot-side MCA (p less than 0.01). The content of
      malondialdehyde was measured by both the thiobarbituric acid test and high
      performance liquid chromatography (HPLC). Comparing the two methods, HPLC proved
      to be more accurate than the thiobarbituric acid test, especially for measurement
      of low concentrations of malondialdehyde. In the placebo-treated group, the
      malondialdehyde content was significantly increased in the Day 7 clot (p less
      than 0.05). In contrast, malondialdehyde content in freshly prepared clot was
      very low. In the 0.3-mg/kg U-74006F group, the malondialdehyde content of clot
      was significantly less at Day 7 compared to clot from the placebo-treated group
      (p less than 0.05). Although the malondialdehyde content of clot from the 1.0
      mg/kg U-74006F-treated group was less than that of placebo, it was not
      significantly so. Malondialdehyde was not detected in the actual vessel wall of
      the MCA of any group. These results suggest that lipid peroxidation in
      subarachnoid clot may play a role in the pathogenesis of vasospasm and that the
      salutary effects of U-74006F in vasospasm may be mediated by a reduction of lipid
      peroxidation in SAH.

PMID- 1993912
TI  - A new model of systemic drug rescue based on permeability characteristics of the
      blood-brain barrier in intracerebral abscess-bearing rats.

PMID- 1993913
TI  - Osteopromotion for cranioplasty. An experimental study in rats using a membrane
      technique.
AB  - Various techniques for treatment of large cranial defects have been reported, but
      the use of alloplastic materials still seems to predominate. The authors have
      applied and explored a new approach for bone repair which appears promising, even
      for use in less osteogenic environments such as the adult calvaria. Seventy-two
      adult Sprague-Dawley rats each received bilateral 8-mm trephine defects in the
      temporoparietal area; this defect size precludes spontaneous osseous healing
      during the lifetime of the animal. Five surgical procedures, employing various
      alternatives of biologically inert expanded polytetrafluoroethylene membrane
      positioning and intramembranous bone-chip implantation, were performed and
      compared to control defects. Slight improvement of bone regeneration was
      demonstrated with subperiosteal ectocranial and endocranial membranes, alone or
      in combination, and with bone chips alone or in combination with an outer or
      inner membrane. Virtually complete bone healing was observed in animals receiving
      both an outer and an inner membrane with interpositioned bone chips. The latter
      appeared to function primarily as space-holders by keeping the membranes
      separated throughout the defect. Consequently, this technique seems to
      significantly promote bone repair by excluding soft-tissue components from the
      bone-healing site.

PMID- 1993914
TI  - Relationship between body and brain temperature in traumatically brain-injured
      rodents.
AB  - Recent work has shown that mild to moderate levels of hypothermia may profoundly
      reduce the histological and biochemical sequelae of cerebral ischemic injury. In
      the present study, the authors examined the effect of fluid-percussion injury on
      brain temperature in anesthetized rats and the effect of anesthesia on brain
      temperature in uninjured rats. The relationship between the brain, rectal, and
      temporalis muscle temperatures during normothermia, hypothermia, and hyperthermia
      was studied following a moderate magnitude of fluid-percussion brain injury (2.10
      to 2.25 atmospheres) in rats. The results showed that mean brain temperature in
      10 anesthetized injured rats, in 21 anesthetized uninjured rats, and in 10
      unanesthetized uninjured rats was a mean (+/- standard error of the mean) of
      36.04 degrees +/- 0.20 degrees C, 36.30 degrees +/- 0.08 degrees C, and 37.95
      degrees +/- 0.09 degrees C, respectively. There was no significant difference in
      temperature under general anesthesia between injured and uninjured rats (p
      greater than 0.05). In the absence of brain injury, mean brain temperature was
      significantly lower in anesthetized rats than in unanesthetized rats (p less than
      0.001). In anesthetized brain-injured rats, temporalis muscle temperature
      correlated well with brain temperature over a 30 degrees to 40 degrees C range,
      even when brain temperature was rapidly changed during induction of hypothermia
      or hyperthermia (r = 0.9986, p less than 0.0001). In contrast, rectal temperature
      varied inconsistently from brain temperature. These observations indicated that:
      1) brain injury itself does not influence brain temperature in this model; 2)
      anesthesia alone decreases brain temperature to levels producing cerebral
      protection in this model; and 3) external monitoring of temporalis muscle
      temperature can provide a reliable indirect measure of brain temperature in the
      course of experimental brain injury. The authors believe that it is essential to
      monitor or control brain temperature in studies of experimental brain injury.

PMID- 1993916
TI  - Superior hypophyseal artery aneurysm. Report of two cases.
AB  - Two cases of saccular intracranial aneurysms arising from the superior
      hypophyseal artery take-off from the internal carotid artery are presented. The
      angiographic findings and technical details of the operative approach are
      discussed. Particular attention is focused on the use of fenestrated angled
      clips.

PMID- 1993915
TI  - Tethered cord syndrome from a choristoma of mullerian origin. Case report.
AB  - The authors report a case of tethered cord syndrome due to a choristoma of
      mullerian origin located in the spinal cord at the lumbosacral junction. Two
      similar cases were found upon review of the literature. The embryology of this
      lesion is discussed.

PMID- 1993917
TI  - Subarachnoid hemorrhage from a dissecting aneurysm of the middle cerebral artery.
      Case report.
AB  - A case of subarachnoid hemorrhage (SAH) from a dissecting aneurysm of the
      inferior limb of the middle cerebral artery is reported. The patient's clinical
      status and the initial and follow-up angiographic appearance of the aneurysm are
      presented. Diagnosis and treatment are briefly discussed. It is suggested that,
      if angiography demonstrates luminal narrowing or vascular occlusion in a patient
      with unexplained SAH, a dissecting aneurysm of the carotid system should be
      considered as a cause of the hemorrhage.

PMID- 1993918
TI  - Intradural chordoma of the tentorium cerebelli. Case report.
AB  - A rare case of intradural chordoma is described. The literature contains seven
      examples of intradural extraosseous chordoma, all reported in a ventral location.
      This is the first reported case of a primary intradural chordoma distant from the
      clivus and involving both the supra- and infratentorial compartments.

PMID- 1993919
TI  - Hemangiopericytoma of the sciatic nerve. Case report.
AB  - The authors report the case of a hemangiopericytoma arising in a sciatic nerve.
      It was found to be invasive within the epineurium but sparing surrounding
      tissues. Adequate resection required sacrifice of the nerve. Hemangiopericytomas
      can be added to the short list of mesodermal peripheral-nerve tumors.

PMID- 1993920
TI  - A vascular malformation mimicking an intracanalicular acoustic neurilemoma. Case
      report.
AB  - A patient with an enhancing, completely intracanalicular mass on magnetic
      resonance imaging was operated on for a presumed acoustic neurilemoma, but was
      found at surgery to have an intracanalicular vascular malformation. This rare
      lesion should be distinguished from angiomatous change within an acoustic
      neurilemoma and in the past has been termed "vascular tumor," "hemangioma," or
      "fibro-angioma." The clinical distinctions between intracanalicular acoustic
      neurilemomas and intracanalicular vascular malformations and the ability of
      magnetic resonance imaging to distinguish between the two are discussed.

PMID- 1993921
TI  - Removal of the roof of the external auditory meatus in approaching the tentorial
      notch through a low temporal craniotomy. Technical note.
AB  - Improved access to the tentorial notch can be obtained by removal of the roof of
      the external auditory meatus in association with a low temporal craniotomy. This
      approach decreases temporal lobe retraction and the risk of venous infarction.
      This method was perfected in the surgical laboratory on five cadavers and was
      successfully performed in a patient with a giant aneurysm of the posterior
      cerebral artery.

PMID- 1993922
TI  - Role of surgery in malignant gliomas.

PMID- 1993923
TI  - Angiographic occult vascular malformations.

PMID- 1993924
TI  - Air embolism: Bodenstab tourniquet.

PMID- 1993925
TI  - Morphine pump and Medicare.

PMID- 1993926
TI  - Foreign-body "gauzomas".

PMID- 1993927
TI  - Quality monitoring and evaluation in staff development.
AB  - Nursing staff development is a vital business within the Division of Nursing and
      must define its scope to include its service, staff, and systems. Critical to any
      business is quality management. This includes a mechanism for standards
      development, evaluation, and response. The purpose of this article is to provide
      direction to the evaluation and response aspects by integrating the dimensions of
      the business of staff development with the Joint Commission on Accreditation of
      Healthcare Organizations' ten-step monitoring and evaluation process. The result
      is a comprehensive quality assurance program that focuses on the important
      aspects of staff development--those that have the most significant impact on
      outcomes.

PMID- 1993928
TI  - Is reading part of the lifelong learning process for RNs?
AB  - A 1988 national survey of 1,406 Registered Nurses (RNs) was conducted at 44 sites
      in 25 states and the District of Columbia to determine what type of occupation
      related and general literature they read, what time they devote to reading, their
      purposes for reading, and the uses of the materials they read. The survey found
      that nurses are reading. They read, purchase, and subscribe to significantly more
      general than professional literature. They report that libraries are accessible,
      but they use them on a limited basis. The RNs also responded that their
      supervisors do not to support them in their pursuit of reading. Clinical
      journals, clinical books, and health-related newsletters are the top nursing
      materials read, newspapers and fiction books the most popular general literature.

PMID- 1993929
TI  - Needs assessment. Process and application.
AB  - This article describes the process of developing a learning needs assessment. The
      process includes developing a tool, collecting data, and analyzing results.
      Understanding the needs assessment process and the pitfalls to avoid may assist
      educators in implementing their own learning needs assessments.

PMID- 1993930
TI  - Computerizing records for continuing education.
AB  - The system was devised as a joint project by members of the Nursing Education
      Department, secretarial staff, and Information Services. The nursing education
      department members identified needed outcomes. The secretaries described what was
      necessary to simplify data entry. The information services personnel had the
      technical expertise to interpret the input from the others and put the system
      together. All members of this project were essential to its development. The
      reports provide information about classes, attendees, and educational budgets.
      The reports also meet requirements of the Joint Commission on Accreditation of
      Healthcare Organizations (JCAHO), Occupational Safety and Health Administration
      (OSHA), and state continuing education regulations.

PMID- 1993932
TI  - Instructional methods.

PMID- 1993931
TI  - A model for participative learning.

PMID- 1993933
TI  - Providers' and consumers' perceptions of quality health care.
AB  - This article describes a study that explored perceptions of quality health care
      among physicians, nurses, patients, and hospital administrators. A self-report
      questionnaire evaluating interpersonal relationships, needs fulfillment, and
      education as dimensions of health care was developed. Results indicated that all
      groups differed in their perceptions of quality health care. Staff development
      educators should be particularly mindful of such differences. Making nurses aware
      of these differences during orientation and continuing education programs can
      assist them more effectively to deliver quality nursing care and meet patients'
      perceived needs.

PMID- 1993934
TI  - Three-dimensional organization of the Golgi complex observed by scanning electron
      microscopy.
AB  - With the development of new specimen preparation techniques and improvements in
      instrumental resolution, scanning electron microscopy (SEM) became an effective
      means of studying the three-dimensional organization of the Golgi complex. When
      specimens prepared by the osmium-DMSO-osmium method are observed with high
      resolution SEMs, cis-most cisternae of Golgi stacks appear as sieve-like plates
      with many small perforations. In some cell types, larger fenestrations are also
      present. The trans-most cisternae showed a fenestrated or retucular pattern. At
      the trans-side of Golgi stacks, distinctive structures, such as a well-developed
      tubular plexus or a single widely extended cisterna, are observed in some types
      of cells. In lacrimal gland cells, Golgi stacks are linked by an irregular
      network of anastomosing branches extending throughout the cytoplasm. In these
      cells, the piled cisternae seemed to be connected to each other either directly
      within the stack or via cisternae of other stacks. Connections between Golgi
      stack and rough endoplasmic reticulum (ER) were often found in our SEM
      observations. In nerve cells, interconnecting tubules arise from the rough ER and
      most often fuse with the rim of the cis-cisternae of Golgi stacks.

PMID- 1993935
TI  - Perspectives on Golgi apparatus form and function.
AB  - In 1898, Camillio Golgi reported a new cellular constituent with the form of an
      extensive intracellular network (the apparato reticolare interno), which now
      bears his name. However, the history of Golgi's apparatus is replete with
      controversy regarding its reality, what components of the cell should be included
      under its aegis, and what terminology should be used when referring to it.
      Electron microscopy has resolved many of these controversies and it is
      appropriate that this volume emphasize that aspect of Golgi apparatus discovery.
      The principal structural component of the Golgi apparatus is the stack of
      cisternae, or dictyosome. As determined both biochemically and at the level of
      electron microscopy, the dictyosome is a highly ordered and polarized structure.
      The maintenance of order within the stack is thought to result from either
      intercisternal bonding constituents, or filamentous structures (or both) that
      bridge the space between adjacent cisternae. Mechanisms proposed for movement of
      membrane and product into and out of the dictyosome (i.e., the Golgi apparatus
      stack) include a serial mode which functions exclusively by the formation,
      displacement, and loss of cisternae from the stack, and a parallel mode which
      functions exclusively by the movement of membrane, product, or precursor
      molecules directly into the peripheral edges of the cisternae. In the parallel
      mode, all cisternae can be accessed either singly or simultaneously, at least in
      theory, at any position within the stack. It is probable that both the serial and
      the parallel modes function concomitantly and need not be mutually exclusive.
      Finally, the peripheral tubules of the cisternae represent a major membranous
      constituent of the cell with potentially unique functions. These tubules
      interconnect cisternae of adjacent stacks and may represent the major site of
      receptors for the shuttle (i.e., parallel) type of transfer among cisternae.
      Peripheral tubules as extensions of the cisternal lumina into the cytoplasm
      presumably have other functions, but these, like the tubules themselves, have
      only rarely been accommodated into functional models of Golgi apparatus dynamics
      in secretion or membrane flow.

PMID- 1993936
TI  - Trans-Golgi reticulum.
AB  - The trans-Golgi apparatus reticulum is that portion of the Golgi apparatus
      located in the trans-most aspect of the stack exhibiting certain characteristic
      morphological and functional characteristics. The membranes of the trans-Golgi
      reticulum are reticular in form, thickened with plasma membrane-like
      characteristics and with a considerable portion of their surface covered by
      clathrin coats. The enzymes thiamine pyrophosphatase and sialyl- and galactosyl
      transferases are functional markers. Correlative studies show the trans-Golgi
      apparatus reticulum to be involved in glycoprotein, enzyme and receptor
      processing and sorting along multiple pathways. Sorting and transfer of
      constituents to lysosomes, to secretory granules, or to the plasma membrane
      emerge as dominant functions.

PMID- 1993937
TI  - Cytochemical characteristics of the Golgi apparatus.
AB  - Lectinocytochemistry provides a useful tool for localizing subcompartments of the
      complex reticular apparatus of Golgi. The technique is based on interactions of
      lectins with glycoconjugates present in the limiting membranes and luminal spaces
      of Golgi elements. Application of a series of lectins of different sugar
      specificities permits a differentiation between Golgi subcompartments containing
      glycoconjugates with different oligosaccharide side chains. These may be a)
      differnet glycoconjugates or b) glycoconjugates at different stages during
      synthesis or repair of their glycans. The lectinocytochemical studies with
      mannose-, glucose-, N-acetyl-glucosamine-, N-acetyl-galactosamine-, galactose-,
      fucose-, and sialic acid-recognizing lectins revealed predominating patterns that
      labeled distinct, i.e., cis, medial, trans, and transmost, regions of the Golgi
      apparatus. A further refinement could be achieved by differential lectin
      inhibition that enables a dissection of lectin binding reactions on the basis of
      their binding affinities. High-affinity binding reactions showed that
      subcompartments are not necessarily confined to one single Golgi subregion and
      may change their position from one to another subregion. Some of the patterns
      observed may be interpreted in relation to certain steps during synthesis and
      modifications of glycans.

PMID- 1993939
TI  - Real space modulation in Bi2Sr2CanCun + 1O6+2n and Tl2Ba2CuO6 superconductors
      derived from electron diffraction information.
AB  - We will try to illustrate here that, simply from the geometry of the electron
      diffraction pattern of an incommensurably modulated structure, conclusive
      information can be obtained on the real space shape of this modulation. The
      method applied here is based on the 3 + 1 dimensional description of symmetry
      operations and can be summarized as follows: 1) reconstruct the three-dimensional
      reciprocal space geometry of the modulated structure from electron diffraction
      information along different zone axes; 2) deduce the complete Bravais type symbol
      of the four-dimensional structure from the general reflection conditions; and 3)
      derive the modulation function for each atom type from the superspace symmetry
      elements which result from the information of both modulation and basic
      structure. This method will be applied here in short on the Bi2Sr2CanCun + 1O6+2n
      strucutre, for which system the results are in agreement with the ones recently
      obtained from neutron diffraction. For Tl2Ba2CuO6 where no data from other
      diffraction techniques are available, a more complete calculation will be
      performed, in order to determine the shape of the displacement function for the
      different atom types; the results are in agreement with the observed High
      Resolution Electron Microscopy (HREM) images.

PMID- 1993938
TI  - Secretory pathways in animal cells: with emphasis on pancreatic acinar cells.
AB  - Studies over the past three decades have clearly established the existence of at
      least two distinct pathways for the intracellular transport and release of
      secretory proteins by animal cells. These have been identified as the regulated
      and constitutive pathways. Many observations have indicated that in certain
      cells, such as those of the exocrine pancreas and parotid glands at least, these
      pathways coexist in the same cells. Although the general scheme of protein
      transport within these pathways is well established, many fundamental aspects of
      intracellular transport remain to be unraveled. How are proteins transported
      through the endoplasmic reticulum? How are the transitional vesicles formed and
      what are the underlying mechanisms involved in their fusion with the cis-Golgi
      cisterna? Even the general mode of transfer through the Golgi stack is debated:
      Is there a diffusion through the stack by flow through intercisternal tubules and
      openings or is there a vesicle transfer system where membrane quanta hop from one
      cisterna to the other? What is the fate of secretory proteins in the trans-Golgi
      area and by what mechanisms is a fraction of newly synthesized molecules of a
      given secretory protein released spontaneously while the majority of such nascent
      molecules are diverted into a secretory granule compartment? In this review, we
      have examined these and other aspects of intracellular transport of secretory
      proteins using pancreatic acinar cells as our reference model and we present some
      evidence to support the existence of a paragranular pathway of secretion
      associated with secretory granule maturation.

PMID- 1993940
TI  - Microwave energy fixation of plant tissue: an alternative approach that provides
      excellent preservation of ultrastructure and antigenicity.
AB  - Immunocytochemical techniques are confronted with the problem of obtaining
      adequate tissue preservation together with retention of protein antigenicity.
      Various methods, including freeze-drying and freeze-substitution, have been
      devised to circumvent this problem. In the present study, we report that
      microwave energy used in combination with low concentrations of glutaraldehyde
      (0.1%) and paraformaldehyde (2%) preserved the structural integrity of plant
      tissue and antigenicity of proteins. Tobacco leaf samples fixed in a time as
      brief as 15-20 s exhibited excellent preservation of fine structures. By
      contrast, specimens irradiated for shorter (5-10 s) or longer (30-40 s) periods
      showed poor morphological preservation. Microwave irradiation for 15-20 s was
      found useful for immobilizing large amounts of soluble antigens. The fast
      microwave fixation method was successfully used to preserve pathogenesis-related
      (PR) proteins, which were subsequently localized by a postembedding immunogold
      procedure. In addition to soluble antigens, cellulose subunits and pectic
      substances, two major plant cell wall components, were found to be highly
      preserved in microwave-irradiated tobacco plant tissue. The present study
      demonstrates that microwave fixation of plant tissue is a simple and inexpensive
      method that is easy to perform with commercially available microwave ovens. The
      incubation time for fixation is reduced from 2 h to 15-20 s without loss of fine
      structural details. This method will undoubtedly acquire increasing applicability
      and relevance in plant biology.

PMID- 1993941
TI  - Principle and applications of convergent beam electron diffraction: a
      bibliography (1938-1990).

PMID- 1993942
TI  - Liver transplantation in pediatrics: indications, contraindications, and
      pretransplant management.

PMID- 1993943
TI  - Clinical and immunologic responses to Haemophilus influenzae type b-tetanus
      toxoid conjugate vaccine in infants injected at 3, 5, 7, and 18 months of age.
AB  - The safety and immunogenicity of Haemophilus influenzae type b-tetanus toxoid
      conjugate vaccine (Hib-TT) were evaluated in 77 healthy infants receiving
      injections at 3, 5, 7, and 18 months of age. No serious local or systemic
      reactions were noted. After the first injection the geometric mean Hib antibody
      level rose to 0.55 micrograms/ml, and each subsequent injection elicited a
      statistically significant rise in the geometric mean. The percentage of vaccinees
      with Hib antibody levels greater than 0.15 micrograms/ml serum was 75.5% after
      the first, 97.4% after the second, and 100% after the third Hib-TT injection.
      This percentage fell to 90.9% at 18 months of age but rose again to 100% after
      the fourth injection. Control infants (n = 10) injected with diphtheria-tetanus
      toxoid-pertussis vaccine only had nondetectable levels after the second
      injection. Hib-TT elicited increases of Hib antibody in all isotypes: IgG greater
      than IgM greater than IgA. Among IgG subclasses the highest increases were of
      IgG1. All vaccinated subjects had greater than 0.01 U/ml of TT antibody
      (estimated protective level) throughout the study. We conclude that Hib-TT,
      injected at 3, 5, 7, and 18 months, is safe and induces protective levels of
      antibodies during the age of highest incidence of meningitis caused by Hib.

PMID- 1993944
TI  - Long-term outcome and prognostic indicators in the hemolytic-uremic syndrome.
AB  - We examined 61 patients an average of 9.6 years (range 5 to 18 years) after an
      episode of childhood hemolytic-uremic syndrome. Twenty-four (39%) had one or more
      abnormalities. Seven (11%) had proteinuria and six (10%) had low creatinine
      clearance as solitary abnormalities. Eight (13%) had both proteinuria and reduced
      creatinine clearance; three (5%) had a combination of hypertension, proteinuria,
      and low creatinine clearance. Abnormalities sometimes appeared after an interval
      of apparent recovery. Logistic regression analysis showed that duration of anuria
      was the best predictor of disease at follow-up. No patients who had anuria
      lasting longer than 8 days or oliguria exceeding 15 days escaped chronic disease.
      However, 45% of those with disease had no anuria, and a third had no oliguria.
      Physicians should therefore be cautious in assuming recovery from HUS on the
      basis of a single evaluation and should periodically evaluate patients for an
      extended period.

PMID- 1993945
TI  - Bronchopulmonary dysplasia: improvement in lung function between 7 and 10 years
      of age.
AB  - To evaluate the natural history of bronchopulmonary dysplasia, we studied the
      same 32 patients at a mean age of 7 and 10 years. The group as a whole had normal
      height and weight percentiles, and each child grew along his or her established
      somatic growth curve. Although some children had abnormal values, the group
      maintained a normal mean total lung capacity and functional residual capacity.
      The mean residual volume and the residual volume/total lung capacity ratios were
      elevated at both ages. At age 7 years the 19 patients (59%) who had a forced
      expiratory volume in 1 second (FEV1) of less than 80% had "catch up" improvement
      by 10 years of age (65 +/- 11% to 72 +/- 16% of predicted value; p less than
      0.05). All the children who had a normal FEV1 at 7 years of age continued to have
      a normal FEV1 at age 10 years. Resting single-breath carbon monoxide uptake by
      the lung was normal when measured at age 10 years. The majority of patients had a
      positive methacholine challenge test result at both ages, although there was a
      low incidence of clinically diagnosed asthma. This study demonstrates that
      patients with bronchopulmonary dysplasia who have normal lung function at age 7
      have had normal lung growth and that those with evidence of mild to moderate lung
      disease have continued lung growth or repair, or both, during their school years.

PMID- 1993946
TI  - Relationship of parental smoking to wheezing and nonwheezing lower respiratory
      tract illnesses in infancy. Group Health Medical Associates.
AB  - The relationship between parental smoking and lower respiratory tract illness
      (LRI) was studied in a large cohort of infants followed prospectively from birth.
      Illnesses were diagnosed by physicians using agreed-on criteria, and parental
      smoking histories were obtained by questionnaire. The LRIs were differentiated
      into wheezing and nonwheezing episodes, and the age at first illness of either
      type was evaluated in relation to smoking by parents. The odds of having an LRI
      were significantly higher in children whose mothers smoked (odds ratio 1.52;
      confidence interval 1.07 to 2.15). The odds were higher if the mother smoked a
      pack of cigarettes or more per day and if the child stayed home rather than
      attending day care (odds ratio 2.8; confidence interval 1.43 to 5.5). Logistic
      regression indicated that the LRI rate was significantly elevated both in
      children exposed to heavy maternal smoke in the absence of day care, and in those
      who use day care but were not exposed to maternal smoking of a pack or more per
      day. These findings could not be attributed to other confounding variables.
      Neither paternal smoking nor smoking by other household members was consistently
      related to the LRI rate. The relationship of maternal smoking to LRI rate was
      evident for both wheezing and nonwheezing illnesses. Maternal smoking of a pack
      or more per day was also related to an early age at first LRI, for both wheezing
      (p less than 0.05) and nonwheezing (p less than 0.002) illnesses. In sum,
      maternal smoking is associated with a higher rate of LRIs in the first year,
      particularly when mothers smoked a pack or more per day and when the child did
      not use day care.

PMID- 1993947
TI  - Influence of parents' physical activity levels on activity levels of young
      children.
AB  - To determine the relationship between activity levels of parents and those of
      their young children, we monitored physical activity with a mechanical device,
      the Caltrac accelerometer, in one hundred 4- to 7-year-old children and in 99 of
      their mothers and 92 of their fathers. During 1 year in the Framingham Children's
      Study, data were obtained for an average of more than 10 hours per day for 8.6 +/
      1.8 days for the children, for 8.3 +/- 2.1 days for their mothers, and for 7.7
      +/- 2.3 days for their fathers. Children of active mothers (average Caltrac
      accelerometer counts per hour greater than the median) were 2.0 times as likely
      to be active as children of inactive mothers (95% confidence interval = 0.9,
      4.5); the relative odds ratio of being active for the children of active fathers
      was 3.5 (95% confidence interval = 1.5, 8.3). When both parents were active, the
      children were 5.8 times as likely to be active (95% confidence interval = 1.9,
      17.4) as children of two inactive parents. Possible mechanisms for the
      relationship between parents' and child's activity levels include the parents'
      serving as role models, sharing of activities by family members, enhancement and
      support by active parents of their child's participation in physical activity,
      and genetically transmitted factors that predispose the child to increased levels
      of physical activity.

PMID- 1993948
TI  - Hypomagnesemia and the parathyroid hormone-vitamin D endocrine system in children
      with insulin-dependent diabetes mellitus: effects of magnesium administration.
AB  - Because insulin-dependent diabetes mellitus is associated with altered
      electrolyte metabolism and a derangement of the parathyroid hormone (PTH)-vitamin
      D endocrine system, we studied 23 children with diabetes (age 9.4 +/- 2.5 years)
      and found lower serum values for total and ionized calcium, magnesium, intact
      PTH, calcitriol, and osteocalcin than in age- and sex-matched control subjects.
      All patients were given magnesium orally (6 mg/kg daily of elemental magnesium)
      for up to 60 days. During treatment, serum magnesium, total and ionized calcium,
      intact PTH, calcitriol, and osteocalcin concentrations significantly increased,
      reaching control values. After a 3-day low-calcium diet, the patients had a
      significantly reduced delta-increment of PTH and calcitriol in comparison with
      values obtained during hypomagnesemia. After magnesium repletion, the delta
      increments of both PTH and calcitriol, in response to the low-calcium diet, were
      not significantly different from control values. These data suggest that
      magnesium deficiency plays a pivotal role in altering mineral homeostasis in
      insulin-dependent diabetes mellitus.

PMID- 1993949
TI  - Dose dependency of time of onset of radiation-induced growth hormone deficiency.
AB  - Growth hormone (GH) secretion during insulin-induced hypoglycemia was assessed on
      133 occasions in 82 survivors of childhood malignant disease. All had received
      cranial irradiation with a dose range to the hypothalamic-pituitary axis of 27 to
      47.5 Gy (estimated by a schedule of 16 fractions over 3 weeks) and had been
      tested on one or more occasions between 0.2 and 18.9 years after treatment.
      Results of one third of the GH tests were defined as normal (GH peak response,
      greater than 15 mU/L) within the first 5 years, in comparison with 16% after 5
      years. Stepwise multiple linear regression analysis showed that dose (p = 0.007)
      and time from irradiation (p = 0.03), but not age at therapy, had a significant
      influence on peak GH responses. The late incidence of GH deficiency was similar
      over the whole dose range (4 of 26 GH test results normal for less than 30 Gy and
      4 of 25 normal for greater than or equal to 30 Gy after 5 years), but the speed
      of onset over the first years was dependent on dose. We conclude that the
      requirement for GH replacement therapy and the timing of its introduction will be
      influenced by the dose of irradiation received by the hypothalamic-pituitary
      axis.

PMID- 1993950
TI  - Community-acquired influenza C virus infection in children.
AB  - To clarify the epidemiologic and clinical features of community-acquired
      influenza C infection in children, we took specimens throughout the year from a
      larger number of patients with acute respiratory illnesses in a pediatric clinic
      in Yamagata, Japan. During a 2-year survey, 20 strains of influenza C virus were
      isolated from 13,426 specimens. These isolates were recovered throughout the
      year. The ages of patients with influenza C virus isolates ranged from 2 months
      to 11 years and peaked at the age of 1 year. The clinical diagnosis of patients
      with influenza C virus infection included bronchitis in one child and pneumonia
      in four. Community-acquired influenza C infection in children can cause a variety
      of respiratory illnesses that cannot be clinically differentiated from those
      caused by other viruses.

PMID- 1993951
TI  - Cystic fibrosis: relationship between clinical status and F508 deletion.

PMID- 1993952
TI  - Inflammatory demyelinating polyneuropathy in a child with symptomatic human
      immunodeficiency virus infection.

PMID- 1993953
TI  - Screening for growth hormone gene deletions in patients with isolated growth
      hormone deficiency.

PMID- 1993954
TI  - Bacterial endocarditis after adjustment of orthodontic appliances.

PMID- 1993955
TI  - Pupil dilation at the first well baby examination for documenting choroidal light
      reflex.

PMID- 1993956
TI  - Transient infantile osteopetrosis.

PMID- 1993957
TI  - Urinary free cortisol values in normal children and adolescents.

PMID- 1993958
TI  - Mineralocorticoids in the mechanism of gynecomastia in adrenal hyperplasia caused
      by 11 beta-hydroxylase deficiency.

PMID- 1993959
TI  - Combined transient and peripheral defects in tetrahydrobiopterin synthesis.

PMID- 1993960
TI  - Cerebral blood flow, cross-brain oxygen extraction, and fontanelle pressure after
      hypoxic-ischemic injury in newborn infants.
AB  - The relationship between mean arterial pressure, intracranial pressure, cerebral
      blood flow, cross-brain oxygen extraction, cerebral metabolic rate, and outcome
      was studied during therapy in nine neonates on 3 consecutive days after severe
      hypoxic-ischemic cerebral injury. Cross-brain oxygen extraction was significantly
      higher (5.06 +/- 0.5 vs 2.05 +/- 0.8 ml/dl; p = 0.012) in the five neonates who
      survived with normal neurologic outcome than in the four who died or sustained
      severe brain damage. In contrast, global cerebral blood flow in the five neonates
      with normal neurologic outcome was significantly lower (25.6 +/- 8.2 vs 83.2 +/-
      44.9 ml/100 gm brain/min; p less than 0.05) during the study period. The
      differences in cross-brain oxygen extraction and global cerebral blood flow
      between infants who had neurologic recovery and those who died or sustained brain
      damage occurred in the presence of acceptable values for intracranial pressure,
      mean arterial pressure, and cerebral perfusion pressure. Our preliminary data
      suggest that cross-brain oxygen extraction and possibly global cerebral blood
      flow may be important variables associated with severe neuronal injury and death
      after hypoxic-ischemic cerebral injury.

PMID- 1993962
TI  - Cerebral blood flow velocity after surfactant instillation in preterm infants.

PMID- 1993961
TI  - Decreased mortality rate among small premature infants treated at birth with a
      single dose of synthetic surfactant: a multicenter controlled trial. American
      Exosurf Pediatric Study Group 1.
AB  - To determine whether a single prophylactic dose of synthetic surfactant would
      reduce mortality and morbidity rates, we performed a randomized, controlled trial
      of Exosurf Neonatal at 19 hospitals in the United States. The Exosurf preparation
      (5 ml/kg) was instilled into the endotracheal tube of premature infants weighing
      700 to 1100 gm during mechanical ventilation, as soon as practical after birth.
      Control infants were treated with air (5 ml/kg). Dose administration was
      performed in secrecy by clinicians who did not reveal for 2 years what they had
      instilled. A total of 222 infants received air and 224 received the synthetic
      surfactant; 36 infants with congenital pneumonia or malformations were excluded
      from the primary efficacy analysis. By the age of 28 days, there were 44 deaths
      in the air group and 27 deaths in the surfactant group (p = 0.022). By the age of
      1 year after term there were 61 deaths in the air group and 35 deaths in the
      surfactant group (p = 0.002). Although there was no reduction in the incidence of
      respiratory distress syndrome, a significant reduction in the number of deaths
      attributed to respiratory distress syndrome, a significant reduction in the
      incidence of pulmonary air leaks, and significantly lower requirements for oxygen
      and mean airway pressure indicated that lung disease was less severe in the
      Exosurf-treated infants. There were no significant differences in the incidence
      of complications such as bronchopulmonary dysplasia, intraventricular hemorrhage,
      patent ductus arteriosus, necrotizing enterocolitis, and infection. The results
      indicate that a single prophylactic dose of Exosurf, in high-risk premature
      infants treated soon after birth, reduces the number of deaths from respiratory
      distress syndrome and the overall mortality rate.

PMID- 1993963
TI  - Dexamethasone in the prevention of postextubation stridor in children.
AB  - To assess whether there is any advantage in the use of corticosteroid to prevent
      postextubation stridor in children, we conducted a prospective, randomized,
      double-blind trial of dexamethasone versus saline solution. The patients were
      evaluated and then randomly selected to receive either dexamethasone or saline
      solution according to a stratification based on risk factors for postextubation
      stridor: age, duration of intubation, upper airway trauma, circulatory
      compromise, and tracheitis. Dexamethasone, 0.5 mg/kg, was given every 6 hours for
      a total of six doses beginning 6 to 12 hours before and continuing after
      endotracheal extubation in a pediatric intensive care setting. There was no
      statistical difference in incidence of postextubation stridor in the two groups;
      23 of 77 children in the placebo group and 16 of 76 in the dexamethasone group
      had stridor requiring therapy (p = 0.21). We conclude that the routine use of
      corticosteroids for the prevention of postextubation stridor during uncomplicated
      pediatric intensive care airway management is unwarranted.

PMID- 1993964
TI  - Diurnal cortisol secretion during therapy with inhaled beclomethasone
      dipropionate in children with asthma.

PMID- 1993965
TI  - Warfarin-nafcillin interaction.

PMID- 1993966
TI  - Respiratory distress and fever in a 2-month-old infant.

PMID- 1993967
TI  - Women and the future of academic pediatrics.

PMID- 1993968
TI  - Indications for psychiatric referral.

PMID- 1993969
TI  - Women in academic pediatrics.

PMID- 1993970
TI  - Acute ifosfamide-induced proximal tubular toxic reaction.

PMID- 1993971
TI  - Aloe vera as a biologically active vehicle for hydrocortisone acetate.
AB  - Aloe vera, as a biological vehicle for hydrocortisone 21-acetate, was tested
      topically and systemically against acute inflammation. Systemically, the
      combination of A. vera and hydrocortisone produced a maximum 88.1% inhibition of
      edema. Polymorphonuclear leukocyte infiltration was reduced 91.1%. The topical
      inhibition of edema peaked at 97%. The possibility that A. vera has significant
      potential as a biologically active vehicle for steroids is discussed.

PMID- 1993972
TI  - Brachymetatarsia. A new surgical approach.
AB  - Although most practitioners are familiar with brachymetatarsia, it is a
      relatively uncommon clinical entity presenting for surgical correction.
      Traditional methods of surgical correction have been successful for the most
      part; however, a number of potentially devastating complications exist with these
      procedures. The authors present a review of the deformity, including the
      historical surgical techniques, and introduce a new surgical approach that
      minimizes the risk of complication.

PMID- 1993973
TI  - Unilateral ectrodactyly, metatarsal synostosis, and hypoplasia in an Eskimo.
AB  - A unilateral foot deformity in an archaeological specimen from Point Hope,
      Alaska, is presented. Radiographic and gross examination of the bones of the
      malformed left foot suggests that this adult female suffered from a rare and
      possibly unique limb deficiency presenting as unilateral congenital absence of
      the phalanges, synostosis and hypoplasia of the metatarsals, and mild hypoplasia
      of the calcaneus.

PMID- 1993975
TI  - Long-term evaluation of partial and total surgical and phenol matrixectomies.
AB  - Surgical matrixectomies and phenol alcohol matrixectomies have been effective in
      eliminating certain nail conditions. The complication rate is at an acceptable
      level; however, there is a need for comparison to other techniques, such as
      negative galvanism, trephine, osteotripsy, and laser ablation. Of the 353
      patients in this study, two were known diabetics who were seen preoperatively by
      a vascular surgeon for vascular studies and by their internist. Both consultants
      agreed that the patients would heal. Both patients healed without complications.
      The author described the use of a modified Frost partial matrixectomy and
      modified Fowler total matrixectomy in this review. The phenol alcohol technique
      had a total complication rate of 9.6%, as did the partial matrixectomy. The total
      matrixectomy had an overall complication rate of 10.9%.

PMID- 1993974
TI  - Chronic tophaceous gout. A case report.
AB  - A review of gout is presented, followed by a discussion of the current medical
      literature on diagnosis, differential diagnosis, staging, and treatment. Chronic
      tophaceous gout is not as prevalent as it once was because of early diagnosis and
      treatment, but it is still encountered in the podiatric practice. A severe case
      of chronic tophaceous gout is presented. The patient was successfully treated by
      surgical intervention. Although surgery may be avoided in most cases, it is
      indicated when intractable pain, loss of motion, and massive joint destruction
      are present.

PMID- 1993976
TI  - Guillain-Barre syndrome during childhood.
AB  - Guillain-Barre syndrome is an acquired disease of the peripheral nervous system.
      The etiology appears to be autoimmune in nature. The major clinical features are
      progressive weakness and loss of reflexes, with respiratory failure being a
      serious complication. The prognosis for Guillain-Barre syndrome in children is
      good with proper intensive care and early detection of the disease.

PMID- 1993977
TI  - Research process. Concluding the research project.
AB  - This fifth article in a series of six on the research process provides guidelines
      for concluding a research project. Attention is directed toward a need for the
      researcher to be sensitive to the persons who supported the project. The other
      significant aspect of concluding a research project involves activities
      associated with analyzing the data, preparing the results, and finalizing the
      findings.

PMID- 1993978
TI  - Research/theory.

PMID- 1993979
TI  - AIDS and needlestick.

PMID- 1993980
TI  - A review of nursing intervention research on maternal adaptation in the first 8
      weeks postpartum.

PMID- 1993981
TI  - The woman with preterm labor at home: a descriptive analysis.

PMID- 1993982
TI  - Searching: expectant fathers' experiences during labor and birth.
AB  - When expectant fathers are present and view labor and birth as a couple
      experience, they are co-laboring in one of three roles: coach, teammate, or
      witness. Within these roles are various degrees and types of engagement. Men in
      the role of coach experience high degrees of physical and mental engagement.
      Teammates fluctuate between high and low degrees of physical and mental
      engagement, and witnesses remain at low degrees of engagement until the second
      stage of labor, when they experience high degrees of mental engagement. The
      expectant fathers' experience is influenced by the labor guides' activities of
      gatekeeping, leading, and informing. Men either maintain or redefine their role
      during labor and birth. Men who experience a sense of not belonging or who are
      uncomfortable with their role will redefine their role by using the strategy of
      searching for place. Searching for place involves the steps of identifying an
      alternative role, engaging in the new role, testing the role, and evaluating the
      effectiveness of the alternative role. Men who experience a sense of belonging in
      their new role will maintain this role. May posed the question, "Is it time to
      fire the coach?" This theory, which requires further testing and validation, does
      address May's question. Perhaps it is not time to fire the coach, as May
      indicated, but it is time to provide couples with options in the role expectant
      fathers play during labor and birth. This theory can guide nurses in relatively
      risk-free interventions for the expectant father. Nurses can assist expectant
      fathers in finding a place in labor and birth that will enhance a mutually
      satisfying birthing experience.

PMID- 1993983
TI  - Are you sleeping? Sleep patterns during postpartum hospitalization.

PMID- 1993984
TI  - VLBW infants: association between visiting and telephoning and maternal and
      infant outcome measures.

PMID- 1993986
TI  - Facilitating parenting of the neonatal intensive care unit graduate.

PMID- 1993985
TI  - Effects of cycled light on activity state and cardiorespiratory function in
      preterm infants.

PMID- 1993987
TI  - Factors affecting reciprocity between nurses and preterm infants during feeding.

PMID- 1993988
TI  - Use of nursing theories in the care of families with high-risk infants:
      challenges for the future.

PMID- 1993989
TI  - The fate of diastereomeric glutathione conjugates of alpha-bromoisovalerylurea in
      blood in the rat in vivo and in the perfused liver. Stereoselectivity in biliary
      and urinary excretion.
AB  - The mixture of the two diastereomeric glutathione (GSH) conjugates of alpha
      bromoisovalerylurea, (RS)-IU-G, was administered i.v. to anesthetized rats. Bile
      and urine were collected for 6 hr. Some 70 to 75% was recovered in urine as
      mercapturates. The half-lives of the urinary excretion were the same for the two
      mercapturates: 18 min and approximately 130 min, respectively, for the rapid and
      the slow phase. In bile only 1.5% of the dose of (R) and (S)-IU-G was found; two
      unidentified metabolites were also found. In rats with ligated kidneys, 4% of the
      dose of each glutathione conjugate was excreted in bile. Again, the two
      unidentified metabolites were found. In the isolated recirculating liver
      perfusion experiments, 1.4% of the administered GSH conjugates was found in bile.
      The concentration of the GSH conjugates in the perfusion medium remained constant
      and no other metabolites were formed. When (RS)-alpha-bromoisovalerylurea itself
      was added to the perfusate, the GSH conjugates in bile increased rapidly. The
      results show that the GSH conjugate in blood is little excreted in bile due to a
      slow uptake of the conjugate by the liver. The diastereomeric GSH conjugates show
      no stereoselectivity in their pharmacokinetics, indicating that the rate limiting
      step in this process is not stereoselective.

PMID- 1993990
TI  - L-651,582 inhibition of intracellular parasitic protozoal growth correlates with
      host-cell directed effects.
AB  - L-651,582 (5-amino-[4-(4-chlorobenzoyl)-3,5-dichlorobenzyl]-1,2,3-triazole-4-
      carboxamide), which is active in vivo against coccidiosis caused by the
      intracellular parasitic protozoan Eimeria tenella, is also effective against this
      organism in tissue culture in Maden Darby bovine kidney (MDBK) host cells. L
      651,582 inhibited 45Ca++ uptake, as well as [3H]hypoxanthine incorporation into
      soluble nucleotide pools, in MDBK cells at concentrations similar to those
      required for antiparasitic activity (IC50 = 0.3 microgram/ml). However, the drug
      did not inhibit the [3H] hypoxanthine incorporation into the nucleotide pools of
      the intracellular E. tenella under the same conditions. The antiparasitic
      activity of several L-651,582 analogs paralleled their ability to inhibit
      [3H]hypoxanthine incorporation in MDBK cells. L-651,582 similarly inhibited the
      growth of the intracellular parasitic protozoan Toxoplasma gondii in vitro with
      either HeLa cells or Normal Human Fibroblasts as host cells. The IC50 for
      inhibition of T. gondii growth in normal human fibroblasts was similar to that
      for [3H]hypoxanthine incorporation inhibition. In HeLa cells, however, 40-fold
      higher levels were required for the inhibition of [3H]hypoxanthine incorporation
      than were required to inhibit parasite growth, showing that antiparasitic
      activity was not a consequence of the alteration in host nucleotide metabolism.
      This was also consistent with the observation that the effect of L-651,582
      against E. tenella in MDBK cells was not reversed by the addition of nutrients
      involved in nucleotide biosynthesis. This study suggests that L-651,582 has
      antiparasitic activity which correlates with host cell effects and which may be a
      result of blocking Ca++ entry in the host cells, but is not the result of an
      alteration of host nucleotide biosynthesis.

PMID- 1993991
TI  - Allosteric interactions at the m1, m2 and m3 muscarinic receptor subtypes.
AB  - The purpose of our study was to investigate the interactions of allosteric
      antagonists at the individual m1, m2 and m3 muscarinic receptor subtypes. This
      was achieved through the use of transformed Chinese hamster ovary cells stably
      expressing the rat m1 or m3 receptor genes. A homogeneous population of the m2
      subtype was obtained from rat heart tissue. Our data indicate that the
      cardioselective antagonists (gallamine, methoctramine, AF-DX 116 and himbacine)
      display the following rank order of potency for both displacing ligand binding to
      the primary site on the receptor and allosterically decelerating ligand
      dissociation: m2 greater than m1 greater than m3. Schild analysis showed the
      following rank order of the magnitude of gallamine's cooperative interactions
      with the three receptor subtypes: m3 greater than m1 greater than m2. By
      comparison, the ion-channel blockers (verapamil, phencyclidine and quinidine)
      exhibited a rank order of potency for cooperative effects similar to that of
      cardioselective antagonists; however, these blockers did not show appreciable
      specificity in their interaction with the receptor primary binding site. There
      was a lack of correlation between the displacement of ligand binding and the
      allosteric potencies of the allosteric antagonists at each of the three
      muscarinic receptor subtypes, thus revealing the complex nature of interaction
      (both competitive and allosteric) between many of these compounds with the
      muscarinic receptor. Despite the fact that the majority of allosteric muscarinic
      antagonists are also K+ channel blockers, the use of pertussis toxin did not
      support the notion that this channel represents the allosteric site coupled to
      the receptor.

PMID- 1993992
TI  - Characterization of K+ channel-dependent as well as -independent components of
      pinacidil-induced vasodilation.
AB  - The mechanisms of pinacidil-induced direct vasodilation were studied in vitro in
      RMA and RAO. In RMA, pinacidil produced dose-dependent relaxations of
      norepinephrine (5 microM)-induced contractions with an IC50 of 0.2 microM. This
      component of pinacidil relaxation appeared to be dependent on K+ conductance
      because pretreatment with tetraethylammonium (10 mM), Ba++ (0.5 mM), glyburide (1
      microM) and 20 mM K+ all caused a rightward shift of the pinacidil dose-response
      curve (DRC) and a corresponding increase in the pinacidil IC50. However,
      additional relaxation effects of pinacidil were still evident in the presence of
      various K+ channel blockers. Pinacidil also showed a relaxation DRC under the
      condition of 80 mM K+ contraction in both RMA and RAO with IC50 values of 27 and
      50 microM, respectively. Pinacidil could also produce maximal relaxation in RMA
      and RAO remained unaffected in 145 mM K+ (zero Na+) depolarizing solution
      suggesting a lack of dependence on Na(+)-Ca++ exchange mechanism for this action
      of pinacidil. Studies using 1 or 3 min pulse labeling with 45Ca showed an absence
      of an inhibitory effect of pinacidil (at 50 and 100 microM) on unidirectional
      45Ca influx stimulated by high-K+. Net 45Ca uptake studies showed that pinacidil
      inhibited high-K+ stimulated 45Ca uptake at 100 but not at 50 microM. Ryanodine
      (10-100 microM) was used as a tool to investigate the role of sarcoplasmic
      reticulum (SR) in this action of pinacidil. Under the condition in which
      ryanodine (10-100 microM) treatment was found to cause the SR to be
      nonfunctional, pinacidil relaxation DRC remained unaltered, suggesting a lack of
      a stimulatory effect of pinacidil on SR Ca++ accumulation. These data thus show
      that the K+ channel-independent effect of pinacidil does not involve to any
      significant degree an effect of pinacidil on plasmalemmal voltage-sensitive Ca++
      channels, SR Ca++ stores, Na(+)-Ca++ exchange or membrane
      hyperpolarization.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1993993
TI  - Reserpine-induced supersensitivity in rat caudal artery: influence of age.
AB  - Vascular smooth muscle function does not necessarily deteriorate with advancing
      age. However, although base-line function may be well maintained, the ability to
      adapt to stress may decline. Therefore we tested the hypothesis that development
      of denervation supersensitivity may be impaired in older animals. Fischer-344
      rats (6, 12, 20, 24 and 27 months old) were treated with reserpine 0.3 or 0.4
      mg/kg i.p. for 7 days, a dose which was sufficient to deplete fully vascular
      norepinephrine content. Isometric contractile responses to phenylephrine and
      serotonin of isolated tail artery rings were determined. In the oldest animals
      studied, 27 months, chronic reserpine treatment resulted in depressed tail artery
      contractile responses, perhaps due to a toxic effect of the reserpine treatment.
      Reserpine-induced supersensitivity, reflected by a decreased EC50, developed to
      both agonists at all other ages studied. For serotonin, the degree of reserpine
      induced supersensitivity did not change with age. However, for phenylephrine, the
      shift in the concentration-response curve after reserpine treatment was less in 6
      month-old rats as compared to all other ages. There was no change in the
      development of supersensitivity from 12 to 24 months of age. These findings
      suggest that the development of reserpine-induced supersensitivity is not
      impaired in blood vessels of older animals and that the ability to adapt to
      changing conditions is also maintained with age.

PMID- 1993994
TI  - Prostaglandin E2-induced diarrhea in mice: importance of colonic secretion.
AB  - The present study has investigated the basis for induction of diarrhea by
      prostaglandin (PG)E2 in mice. When given i.p., PGE2 induced a dose- and time
      dependent diarrhea; the shortest post-treatment time for diarrhea onset was
      approximately 7 min, at a PGE2 dose of 200 micrograms/kg. At this dose, PGE2 also
      produced accumulation of fluid in the small intestine and in the colon
      (enteropooling). The enteropooling reached its maximum by 9 min and did not
      decrease until approximately 11 min (i.e., 2 to 4 min after the mean time for
      diarrhea onset). PGE2 treatment altered neither gastric emptying nor
      gastrointestinal propulsion, but strongly enhanced the expulsion of a glass bead
      from the colon (i.e., decreased the time to bead expulsion). The shortest time to
      expulsion of the glass bead was observed at 200 micrograms/kg i.p. The induction
      of diarrhea by PGE2 was unaffected by cecectomy, or sham-cecectomy, but the dose
      response curve for time to onset of diarrhea by i.p. PGE2 was displaced to the
      right in animals with ligations of the ileo-ceco-colonic (ICC) junctions. The
      intraluminal fluid accumulation in the colon, evaluated in mice with ICC
      ligations, was increased by PGE2 administration within 2 min and remained greater
      than in vehicle-treated animals until the onset of diarrhea. The stimulation of
      colonic bead expulsion produced by i.p. PGE2 in control mice was not observed in
      animals with acute ICC ligations, even at i.p. doses up to 800
      micrograms/kg.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1993995
TI  - Enantiomers of oxybutynin: in vitro pharmacological characterization at M1, M2
      and M3 muscarinic receptors and in vivo effects on urinary bladder contraction,
      mydriasis and salivary secretion in guinea pigs.
AB  - The major side effects of racemic oxybutynin (OXY), which is used in the
      treatment of urinary incontinence are dry mouth (xerostomia) and blurred vision
      (mydriasis). Highly purified enantiomers of OXY [(R)OXY, (S)OXY] were compared
      with the racemate both in vitro in functional studies and in vivo in guinea pigs
      to evaluate their pharmacological action relative to their adverse effects. The
      affinity of (R)OXY and (S)OXY for different muscarinic receptor subtypes was
      determined using field stimulated rabbit vas deferens (M1) and guinea pig atria
      (M2) or bladder (M3) strips. Stereoselective antimuscarinic effects [(R)OXY
      greater than or equal to (R/S) OXY much greater than (S)OXY] were evident at all
      three receptor subtypes; the isomeric ratio [(S)OXY/(R)OXY] ranged from 12 to 88.
      Both (R)OXY and (R/S)OXY were slightly more selective (2-4-fold, P less than .01)
      for M1 and M3 relative to M2 muscarinic receptors. Stereoselectivity was also
      evident in vivo for volume-induced urinary bladder contractions as measured by
      cystometrogram parameters [(S)OXY/(R)OXY approximately 21], mydriasis
      [(S)OXY/(R)OXY approximately 136] and salivary gland secretory responses
      [(S)OXY/(R)OXY approximately 30]. The absolute potencies of (R)OXY or (R/S)OXY
      for mydriasis and salivation were similar to those for inhibition of intravesical
      bladder pressure. Also, (R)OXY and (R/S)OXY equipotently antagonized cholinergic
      mediated CNS effects in mice. Collectively, the data suggest that the activity of
      (R/S)OXY resides predominantly in the (R)-enantiomer. However, it appears that
      (R)OXY may offer no significant pharmacological advantage over (R/S)OXY in terms
      of its principal therapeutic and side effect profile.

PMID- 1993996
TI  - Micropuncture evaluation of the site of action of 2-aminomethyl-4-(1,1
      dimethylethyl)-6-iodophenol hydrochloride (MK447) in the rat kidney.
AB  - Free-flow micropuncture and in situ microperfusion techniques were used to define
      the site of action and relative effect of MK447 [2-aminomethyl-4-(1,1
      dimethylethyl)-6-iodophenol hydrochloride] vs. furosemide in the rat kidney.
      MK447 was administered i.v. at 5 mg/kg/hr. Infusion of this drug had little
      effect on proximal tubule reabsorption of water, Na+ and K+. In contrast,
      reabsorption of these constituents by the loop of Henle was significantly
      reduced. There was a tendency for water and Na+ reabsorption to rise and for K+
      secretion to fall along the distal tubule. These latter effects can be explained
      by the contributions of an increased distal flow rate and increased tubule fluid
      K+ concentration. Net addition of K+ beyond the distal tubule was observed. This
      may be due to effect of the drug on the collecting duct system or juxtamedullary
      nephrons. The effects of MK447 and furosemide on loop of Henle reabsorption were
      compared in microperfusion experiments. Furosemide reduced Na+, K+ and water
      reabsorption by the loop, whereas MK447 had no effect. A 6-bromophenol sulfate
      ester of MK447 significantly reduced loop reabsorption. From these observations,
      we conclude that MK447 affects water and electrolyte reabsorption by the loop of
      Henle and beyond the superficial late distal tubule. The fact that a potential
      metabolite, but not MK447, significantly reduced reabsorption by the in situ,
      perfused loop of Henle supports the hypothesis that the p.o. and i.v. effects of
      MK447 are dependent on metabolism.

PMID- 1993997
TI  - Extremely long protection by pyrazole derivatives against chemically induced
      gastric mucosal injury.
AB  - We tested the hypothesis that the gastrotoxicity of ethanol and other damaging
      agents is influenced through the modulation of alcohol dehydrogenase (ADH) by
      using either the ADH-inhibitor pyrazole or the noninhibitor derivatives of
      pyrazole. In time course experiments, the protection by both compounds was
      evident up to 48 hr before ethanol administration. Both drugs were also
      protected, from about 24 hr, from gastric mucosal damage induced by aspirin and
      hydrochloric acid. In order to examine the role of endogenous prostaglandins and
      sulfhydryls in this protection, indomethacin and N-ethylmaleimide were used, of
      which only the sulfhydryl alkylator antagonized (by about 50%) the protection by
      pyrazole and 3-methylpyrazole. Studies with monastral blue B revealed the
      protective role of both pyrazole and 3-methylpyrazole against early vascular
      injury in the gastric mucosa. We conclude that because both the ADH-inhibitor
      pyrazole and the noninhibitor derivatives of pyrazole exert gastro-protection,
      and because both compounds protect against aspirin and HCI, ADH inhibition is not
      involved in this protection. We also suggest that although prostaglandins appear
      to have minimal involvement in the mechanism of protection, endogenous
      sulfhydryls may be important mediators. Furthermore, the functional and
      structural mechanism of this protection seems to be the prevention of acute
      vascular injury.

PMID- 1993998
TI  - Comparative effects of angiotensin II and angiotensin III in rabbit adrenal and
      aortic tissues.
AB  - The addition of angiotensin II (AII) and angiotensin III (AIII) to isolated
      tissue baths produced the same maximal contractile response of rabbit aortic
      strips. AIII was about 10 times less potent, the slope of its concentration
      response curve was less steep and its rate of onset slower than that of AII. The
      responses of both AII and AIII were inhibited with equal potency by the
      surmountable AII antagonist Phe4, Tyr8-AII and its unsurmountable analog Sar1,
      Leu8-AII but the kinetic patterns of inhibition by both were less well defined
      with the agonist AIII than with AII. The addition of AIII to tissues which had
      exhibited a maximal response to AII did not increase the level of contraction, in
      contrast to the case when norepinephrine was added to tissues contracted by AII.
      Both AII and AIII displaced [125I]AII binding from rabbit adrenal membranes; AIII
      was 6 times less potent than AII but displayed competitive kinetics as an
      inhibitor of [125I]AII binding. In further studies two binding sites for
      [125I]AII were identified in adrenal membranes, having KD values of 2.0 +/- 0.2
      and 19.6 +/- 2.3 nM, respectively. Each site was inhibited by both AII and AIII
      and the ratio of the apparent Ki values for the two hormones was not
      significantly different. The Hill coefficient for the high affinity site was,
      however, lower for AIII than AII. We interpret our data to suggest that AII and
      AIII act on the same receptors. AIII apparently binds less efficiently than does
      AII in both rabbit adrenal membranes and rabbit aortic strips.

PMID- 1993999
TI  - Cardiac adenylate cyclase activity, positive chronotropic and inotropic effects
      of forskolin analogs with either low, medium or high binding site affinity.
AB  - A series of in vitro studies were conducted examining the adenylate cyclase
      stimulation, positive chronotropic and inotropic effects of forskolin and nine
      analogs which exhibited a range of [3H]forskolin binding site affinities (K1)
      from 0.020 to 3.174 microM. A significant (P less than .001) linear correlation
      (r = 0.94) was found between binding site affinity and adenylate cyclase
      stimulation (EC50) for forskolin and the nine structural analogs. Adenylate
      cyclase activity was also significantly correlated with the positive chronotropic
      and inotropic effects of these substances on isolated guinea pig atria. Compounds
      with K1 values between 0.020 and 1.136 microM produced concentration-dependent
      increases in heart rate and contractile force in isolated spontaneous and
      electrically paced guinea pig atria, respectively. In contrast, an analog with a
      K1 of 3.174 microM caused significant (P less than .05) negative chronotropic and
      inotropic effects at concentrations above 10 microM. The optimal separation
      between positive inotropic and chronotropic activity was found with compounds
      displaying potent [3H]forskolin binding site affinity but moderate adenylate
      cyclase stimulation, i.e., K1 and EC50 values of approximately 0.05 to 0.10 and 3
      microM, respectively. The results of this study show that the forskolin analog,
      P87-7692 [7-desacetyl-7-(O-propionyl)-hydroxyl amino-carbonyl-forskolin], has
      marked activity with a wide separation between positive inotropic (248 +/- 41%)
      and chronotropic effects (43 +/- 13%) at 6.2 microM and may serve as a prototype
      for a forskolin-based cardiotonic.

PMID- 1994000
TI  - Hydrolysis of [Leu]enkephalin by chick plasma in vitro.
AB  - The in vitro hydrolysis of [Leu]enkephalin added to plasma collected from 2-day
      old chicks was studied with two different techniques: thin-layer chromatography
      separation of intact [3H]-[Leu]enkephalin from its [3H]-Tyr-containing
      metabolites and high-performance liquid chromatography-electrochemical detection
      assay of [Leu]enkephalin disappearance and Tyr-containing metabolite
      accumulation. The radiometric assay evaluated enkephalin hydrolysis at close to
      presumed physiological concentrations of this peptide, whereas the liquid
      chromatography assay necessitated 100-fold higher peptide concentrations to
      achieve adequate sensitivity. Similar results were obtained with both techniques.
      We found that the in vitro hydrolysis of [Leu]enkephalin is more rapid in chick
      plasma (half-life, 0.7-1 min) than in rat (half-life, 2-2.5 min) or mouse (half
      life, 9-14 min) plasma. Comparison of the rate of enkephalin hydrolysis and
      pattern of metabolite accumulation in the absence vs. the presence of various
      peptidase inhibitors suggested that a bestatin-sensitive aminopeptidase, probably
      aminopeptidase M, is the primary enzyme responsible for the hydrolysis of
      enkephalin by chick plasma, and that less than 1% of the total hydrolysis of
      [Leu]-enkephalin by chick plasma is attributable to dipeptidyl carboxy-peptidase
      activity. This pattern of enzyme activities differs from that which we identified
      previously in rat and mouse plasma.

PMID- 1994002
TI  - Antagonist binding profiles of five cloned human muscarinic receptor subtypes.
AB  - A variety of muscarinic antagonists are currently used as tools to
      pharmacologically subclassify muscarinic receptors into M1, M2 and M3 subtypes.
      In the present study, we have determined the affinity profiles of several of
      these antagonists at five cloned human muscarinic receptors (m1-m5) stably
      expressed in Chinese hamster ovary cells (CHO-K1). At all five receptors, the (R)
      enantiomers of trihexyphenidyl and hexbutinol displayed considerably higher
      affinities (up to 525-fold) than their corresponding (S)-isomers. The
      stereoselectivity ratios [inhibition constant(S)/inhibition constant(R)] for both
      pairs of enantiomers were lowest at m2 receptors, suggesting that less stringent
      configurational demands are made by this receptor subtype. The "M1-selective"
      antagonist (R)-trihexyphenidyl displayed high affinities for m1 and m4 receptors.
      The "M2-selective" antagonists himbacine, (+-)-5,11-dihydro-11- ([(2
      [(dipropylamino)methyl]-1- piperidinyl)ethyl)amino]carbonyl)-6H-pyrido(2,3
      b)(1,4)benzodiazepine-6- one (AF-DX 384), 11-[4-[4-(diethylamino)butyl]-1
      piperidinyl)acetyl)-5,11- dihydro-6H-pyrido(2,3-b) (1,4)benzodiazepine-6-one (AQ
      RA 741) and (+)-(11-[2-[(diethylamino) methyl]-1-piperidinyl)acetyl)-5,11-di
      hydro-6H-pyrido(2,3-b)(1,4) benzodiazepine-6-one [AF-DX 250; the (+)-enantiomer
      of AF-DX 116] exhibited high affinities for m2 and m4, intermediate affinities
      for m1 and m3 and low affinities for m5 receptors. This selectivity profile was
      most prominent for AQ-RA 741, which displayed 195- and 129-fold higher affinities
      for m2 and m4 receptors than for m5 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1994001
TI  - Endothelium-independent and endothelium-dependent contractions mediated by P2X-
      and P2Y-purinoceptors in canine basilar arteries.
AB  - Both alpha, beta-methylene ATP and beta, gamma-methylene ATP (P2X selective
      agonists) were shown to induce transient contraction in intact and endothelium
      removed preparations of canine basilar arteries. 2-Methylthio ATP (a P2Y
      selective agonist) caused transient contraction of intact arteries and this
      response was nearly abolished by removal of the endothelium. In the presence of
      alpha, beta-methylene ATP (10(-6) M), the endothelium-independent contractions
      induced by alpha, beta-methylene ATP itself (10(-6) M) and by beta, gamma
      methylene ATP (10(-5) M) were both abolished. The endothelium-dependent
      contraction induced by 2-methylthio ATP (10(-7) M) was not attenuated by alpha,
      beta-methylene ATP. The contraction induced by 2-methylthio ATP (10(-7) M) was
      attenuated markedly by reactive blue 2 (a P2Y antagonist) (3 x 10(-6) M), aspirin
      (5 x 10(-5) M), OKY-046 (thromboxane A2 synthetase inhibitor) (10(-5) M) and ONO
      3708 (thromboxane A2 antagonist) (10(-8) M). However, these agents did not affect
      the endothelium-independent contraction induced by alpha, beta-methylene ATP (10(
      6) M). Neither TMK-777 (a 5-lipoxygenase inhibitor) (10(-7) M) nor superoxide
      dismutase (100 U/ml) plus catalase (1,000 U/ml) affected either contraction. The
      present experiments demonstrate that P2X-purinoceptors mediate endothelium
      dependent contraction in the canine basilar artery, and that the endothelium
      derived contracting factor in this system is probably thromboxane A2.

PMID- 1994003
TI  - Pharmacological characteristics of high-affinity serotonin uptake systems
      established through gene transfer.
AB  - Inactivation of a neurotransmitter, after its stimulated release, via high
      affinity uptake mechanisms is an essential regulatory step of neurotransmission
      in both the central and peripheral nervous systems. To initiate explorations of
      the molecular mechanisms and the underlying biochemical architecture of high
      affinity neurotransmitter uptake systems, we have used gene transfer technology
      to establish and identify novel cellular models that express these systems. Human
      genomic DNA was transfected into mouse L-M fibroblasts and two independently
      arising, clonal cell lines (L-S1 and L-S2) have been identified as expressing
      high-affinity serotonin (5-HT) uptake systems. The 5-HT uptake characteristics of
      L-S1 and L-S2 are essentially comparable (in terms of Na+ dependence, temperature
      sensitivity, imipramine antagonizability, kinetic saturability and high
      affinities) and those of L-S1 have been reported previously. Furthermore,
      competition studies utilizing catecholamine neurotransmitters and their amino
      acid precursors demonstrated that these systems are highly specific for 5-HT.
      Several known inhibitors of high-affinity 5-HT uptake systems (including
      amitriptyline, desipramine, fluoxetine, imipramine, nortriptyline, tryptamine, 5
      methoxytryptamine and N-acetyl 5-methoxytryptamine) were assessed in terms of
      their respective potencies to inhibit 5-[3H]HT uptake by L-S1 and L-S2 cells. For
      L-S1 cells, the rank order of inhibitor potencies is imipramine greater than
      amitriptyline greater than fluoxetine greater than desipramine = nortriptyline
      greater than tryptamine greater than 5-methoxytryptamine greater than N-acetyl-5
      methoxytryptamine. For L-S2, the rank order is similar to that of L-S1 except
      that fluoxetine is more potent than amitriptyline.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1994004
TI  - Behavioral and neurochemical changes in rats dosed repeatedly with
      diisopropylfluorophosphate.
AB  - Behavioral effects of organophosphates (OPs) typically decrease with repeated
      exposure, despite persistence of OP-induced inhibition of acetylcholinesterase
      (AChE) and downregulation of muscarinic acetylcholine (ACh) receptors. To
      characterize this tolerance phenomenon, rats were trained to perform an
      appetitive operant task which allowed daily quantification of working memory
      (accuracy of delayed matching-to-position), reference memory (accuracy of visual
      discrimination) and motor function (choice response latencies and inter-response
      times during delay). Daily s.c. injections of 0.2 mg/kg of
      diisopropylfluorophosphate (DFP) caused no visible cholinergic signs, did not
      affect body weight or visual discrimination, but progressively impaired matching
      accuracy and lengthened response latencies and interresponse times. These effects
      recovered in seven of eight treated rats after termination of DFP treatment.
      Resumption of daily DFP at 0.1 mg/kg caused smaller impairments of both matching
      accuracy and response latency. After 21 injections of 0.2 mg/kg/day of DFP, rats
      were subsensitive to the hypothermia induced by acute oxotremorine (0.2 mg/kg
      i.p.), as expected after OP-induced downregulation of muscarinic ACh receptors.
      Evidence for supersensitivity to scopolamine (0.03 and 0.056 mg/kg i.p.) in DFP
      treated rats was mixed, with additive effects predominating on both the cognitive
      and motor aspects of the task. After 18 days of 0.1 mg/kg of DFP, AChE was
      inhibited 50 to 75% and muscarinic ACh receptor density was reduced 15 to 20% in
      hippocampus and frontal cortex. Progressive declines in AChE activity in
      hippocampus and frontal cortex across 15 daily doses with DFP at 0.1 and 0.2
      mg/kg were observed in other rats; quinuclidinyl benzilate binding was
      significantly reduced in hippocampus after 15 doses at both levels of DFP. These
      results indicate that animals showing a definitive sign of tolerance to OP
      administration (subsensitivity to a cholinergic agonist) were also functionally
      impaired on both the mnemonic and motoric demands of a working memory task. The
      nature of this impairment suggests further that it results from compensatory
      changes in the central nervous system, e.g., muscarinic receptor downregulation,
      considered to produce "tolerance" to OPs in exposed animals.

PMID- 1994005
TI  - Myocarditis--a controversial disease.

PMID- 1994006
TI  - Children in shipping disasters.

PMID- 1994007
TI  - Psychiatric response to the Clapham rail crash.
AB  - The psychiatric response to the Clapham rail crash is described. The psychiatric
      input was short term, dealing with the 38 inpatients and over 200 hospital staff
      involved in the response. The need to evolve a compact, responsive team structure
      is noted. The value of a proactive approach and provision of psychological
      debriefing is defended. Incorporation of components of the psychiatric response
      into the Hospital's major incident plan is reported.

PMID- 1994008
TI  - Theoretical issues in responses to disaster.

PMID- 1994009
TI  - Emotional sequelae of sexual assault.

PMID- 1994010
TI  - Arthroscopy in children.
AB  - Arthroscopy was performed on the knees of 67 children aged 2-16 years with an
      overall clinical diagnostic accuracy of 45%. The most common clinical diagnoses
      were meniscal tear and patello-femoral pain and the accuracy of these diagnoses
      was 33% and 59% respectively. Diagnostic accuracy seemed unrelated to age.
      Arthroscopy led to definitive treatment which relieved symptoms in 21 (31%) of
      cases, revealed a diagnosis only in 43 (64%), and was non-contributory in 3
      (4.5%). The procedure did not significantly help patients with patello-femoral
      pain.

PMID- 1994011
TI  - Causes and mortality in patients aged over 75 years with gastrointestinal
      haemorrhage.
AB  - One hundred and fifty-five patients aged 75 years and over with gastrointestinal
      haemorrhage were studied and compared with a series of patients aged under 75
      years. The mortality in patients with gastric ulcer or gastric carcinoma was not
      affected by age. However, the mortality in patients with duodenal ulcer was
      greater in the over-75s (8/31 deaths in the over-75s, 4/77 deaths in the under
      75s, P = 0.01). There was no reluctance to operate on the over-75s. These results
      can be used to help construct future trials to improve treatment.

PMID- 1994012
TI  - Bowel distress and emotional conflict.
AB  - A psychodynamic assessment of 60 women with functional bowel disorder seen at St
      Mark's, a specialist hospital for disorders of the colon and rectum, has shown
      that most were trapped in severe emotional conflicts with which they were unable
      to cope. In many the bodily illnesses appeared to be an expression of these
      conflicts as well as a defence against experiencing them. The illnesses were then
      partly, or entirely, emotional conflicts that had become medicalized--emotional
      conflicts in illnesses clothing. The illnesses, usually precipitated by
      significant life events, often had their roots in emotional conflicts in infancy
      or childhood at which time a high proportion of the women had experienced a
      severe life trauma. The study also indicated that the conflicts that appeared to
      contribute to the illnesses were associated with emotional difficulties in
      fulfilling themselves as women.

PMID- 1994013
TI  - Psychological aftermath of the King's Cross fire.
AB  - The King's Cross fire occurred at the end of the evening rush hour, on 18
      November 1987. King's Cross station is within the department's health district
      and we felt a responsibility to respond to the psychological aftermath. The
      unique features of our intervention were the degree of inter agency coordination,
      the use of a systematic outreach and screening programme, the collection of
      psychotherapy outcome measures and the development of an ongoing clinic. The work
      represents a sustained attempt to assess the nature and prevalence of post
      traumatic reactions and the most medically and economically effective form of
      intervention. In this paper we describe the way our team responded to the high
      level of psychological distress that we found, we present some preliminary
      results, outline two therapeutic trials, and refer to the longterm consequences
      for the work of our department.

PMID- 1994014
TI  - Why do hospital doctors wear white coats?
AB  - Seventy-two per cent of all hospital doctors and medical students wear white
      coats and most wear them greater than 75% of the time. White coats are worn
      chiefly for easy recognition by colleagues and patients, to put items in the
      pockets and to keep clothes clean. Psychiatrists and paediatricians try to
      maximize rapport with patients by deliberately not wearing white coats.

PMID- 1994015
TI  - Sir Samuel Wilks: a founding father of clinical science.

PMID- 1994016
TI  - Facial desmoplastic malignant melanoma.

PMID- 1994017
TI  - Toxic shock syndrome presenting as an acute encephalopathy and diarrhoea.

PMID- 1994018
TI  - Fournier's gangrene of the scrotum following day case vasectomy.

PMID- 1994019
TI  - Gastric sarcoidosis.

PMID- 1994021
TI  - Assessment of chronic snorers.

PMID- 1994020
TI  - Mania and recovery from chronic fatigue syndrome.

PMID- 1994022
TI  - Immunology of the tonsils.

PMID- 1994023
TI  - Osler's robes.

PMID- 1994024
TI  - Three dimensional thallium-technetium scans.

PMID- 1994025
TI  - Advanced head and neck cancer.

PMID- 1994027
TI  - I don't fancy cheiromancy.

PMID- 1994026
TI  - Non-specific abdominal pain--an expensive mystery?

PMID- 1994028
TI  - Saint Vitus' dance.

PMID- 1994029
TI  - Lithium increases actin polymerization rates by enhancing the nucleation step.
AB  - Lithium affects the polymerization mechanism of some cytoskeletal proteins in
      vitro, so its biological activity could also reflect lithium influence on
      assembly processes. Our data demonstrate that lithium nucleates actin
      polymerization and, in parallel, is less effective in the elongation step.
      Furthermore, falling-ball and fluorimetric tests suggested that lithium-induced
      actin polymers at steady-state are shorter than K(+)-polymerized actin
      filamentous structures. The lithium-induced actin assembly seems to follow the
      "reversible polymerization model" and the critical concentration of Li(+)
      assembled actin at steady-state is markedly lower than that of sister actin
      samples polymerized by potassium chloride. Finally, the stabilization of actin
      nuclei induced by lithium ions could be related to their effect of lowering the
      dissociation rate constant.

PMID- 1994030
TI  - Angular disorder in actin: is it consistent with general principles of protein
      structure?
AB  - Harold Erickson has recently provided a useful analysis of helical structures
      having one class versus two classes of intersubunit bonds. His analysis is based
      upon an assumption that the subunits themselves are essentially unchanged upon
      bond formation (polymerization). He shows that such a structure having two
      classes of bonds (i.e. one in which each subunit interacts with four of its
      neighbors rather than two) can explain some of the features of actin. While he
      acknowledges that for actin there could be a conformational change and that, in
      principle, it could explain such features, he argues that the allowed magnitude
      of such a conformational change is inadequate. Since kinetics and thermodynamics
      cannot distinguish between the energy derived from the formation of a bond from
      that due to a conformational change, the question of whether the features of F
      actin are derived from a conformational change or a system of two classes of
      bonds or both must be answered with high-resolution structural information.
      Recent studies by K. C. Holmes and others suggest that the second possibility
      might be closest to the truth. The heart of our disagreement is not whether
      Erickson's thermodynamic analysis is correct, given rigid subunits, but whether
      all protein polymers are characterized by rigid subunits with rigid intersubunit
      contacts. Erickson maintains that the observation of an angular disorder of 12
      degrees per subunit within the actin filament conflicts with his formalism of
      rigid subunit interfaces and must therefore result from the erroneous
      interpretation of measurements. He presents an alternative model to explain the
      observations. His model, however, does not account for the observations and we
      will argue that, ultimately, like the resolution of the matter of the number of
      classes of bonds and the extent of their contact, the amount of angular disorder
      will require higher-resolution structural studies.

PMID- 1994031
TI  - X-ray crystal structure of the ferric sperm whale myoglobin: imidazole complex at
      2.0 A resolution.
AB  - The X-ray crystal structure of the ferric sperm whale (Physeter catodon)
      myoglobin:imidazole complex has been refined at 2.0 A resolution, to a final R
      factor of 14.8%. The overall conformation of the protein is little affected by
      binding of the ligand. Imidazole is co-ordinated to the heme iron at the distal
      site, and forces distinguishable local changes in the surrounding protein
      residues. His64(E7) swings out of the distal pocket and becomes substantially
      exposed to the solvent: nevertheless, it stabilizes the exogenous ligand by
      hydrogen bonding. The side-chains of residues Arg45(CD3) and Asp60(E3) are also
      affected by imidazole association.

PMID- 1994032
TI  - Computer simulation of DNA supercoiling.
AB  - We treat supercoiled DNA within a wormlike model with excluded volume. A modified
      Monte Carlo approach has been used, which allowed computer statistical-mechanical
      simulations of moderately and highly supercoiled DNA molecules. Even highly
      supercoiled molecules do not have a regular shape, though with an increase in
      writhing the chains look more and more like branched interwound helixes. The
      averaged writhing (Wr) approximately 0.7 delta Lk. The superhelical free energy F
      is calculated as a function of the linking number. Lk. The calculations have
      shown that the generally accepted quadratic dependence of F on Lk is valid for a
      variety of conditions, though it is by no means universal. Significant deviations
      from the quadratic dependence are expected at high superhelical density under
      ionic conditions where the effective diameter of DNA is small. The results are
      compared with the available experimental data.

PMID- 1994033
TI  - Construction, expression and release of hybrid colicins.
AB  - Colicins A and E1 are two pore-forming colicins sharing homology in their C
      terminal domains but not in their N-terminal or central domains. Using site
      directed mutagenesis, restriction sites were inserted at the proper locations to
      allow recombination of these domains. Six different constructs were obtained. All
      these proteins were expressed in Escherichia coli and properly recognized by
      monoclonal antibodies directed against epitopes located in different domains of
      colicin A. Out of the six hybrids, only two were released to the extracellular
      medium. Immunocytolocalization indicated that some of the hybrids aggregated
      within the cytoplasm. With some hybrids, the defect in release was related to a
      defect in synthesis of the lysis protein that normally promotes release.

PMID- 1994034
TI  - Analysis of the membrane organization of an Escherichia coli protein
      translocator, HlyB, a member of a large family of prokaryote and eukaryote
      surface transport proteins.
AB  - Haemolysin B (HlyB) is essential for secretion of the 107 x 10(3) Mr haemolysin A
      protein from Escherichia coli and is a member of a family of highly conserved,
      apparently ATP-dependent surface proteins in many organisms. We have shown in
      this study that both HlyB and HlyD fractionate primarily with the cytoplasmic
      membrane of E. coli and are accessible to proteases after removal of the outer
      membrane. We have measured experimentally the topological organization of HlyB
      within the membrane by construction of fusions to beta-lactamase as a reporter.
      The predicted folding of HlyB, with a minimum of six transmembrane segments, does
      not always coincide with regions of highest average hydrophobicity. This suggests
      that HlyB may have a novel organization within the bilayer. From our data and
      comparative sequence analysis, we have been able to predict very similar
      topological models for the other members of the HlyB family.

PMID- 1994035
TI  - Functional and structural effects of an Ala to Val mutation in the adenovirus
      serotype 2 fibre.
AB  - H2ts125 is a fibre-defective, temperature-sensitive mutant of adenovirus serotype
      2. H2ts125 fibre is unstable at the non-permissive temperature (ts phenotype),
      and does not migrate in the same way as the wild-type fibre in an
      SDS/polyacrylamide gel (elm phenotype). Sequence analysis has shown that H2ts125
      carries two mutations on the fibre gene: Leu105 to Phe, and Ala434 to Val.
      Analysis of the structural modifications occurring in H2ts125 fibre was performed
      using peptide finger-printing and antipeptide sera as immunological probes. We
      found that all the detectable structural alterations in the mutant fibre were due
      to the substitution on codon 434. In addition, the ts phenotype was rescued by a
      wild-type DNA fragment containing the 3' moiety of the fibre gene and overlapping
      the 434th codon. Morphological analysis of fibre molecules observed under the
      electron microscope showed minor but statistically significant differences in the
      fibre length between mutant and wild-type. The mutant fibre was found to be
      slightly longer (308.8 +/- 1.9 A) than the wild-type fibre (300.1 +/- 2.1 A).
      Thus both ts and elm phenotypes were carried by the same Ala434 to Val mutation
      which probably resulted from a change in the three-dimensional structure of the
      fibre protein, and not from some proteolytic cleavage.

PMID- 1994036
TI  - Three-dimensional spatial relationship between the collagen fibrils and the
      inorganic calcium phosphate crystals of pickerel (Americanus americanus) and
      herring (Clupea harengus) bone.
AB  - High-voltage (1.0 MV) electron microscopy and stereomicroscopy, electron probe
      microanalysis, electron diffraction and three-dimensional computer
      reconstruction, have been used to examine the spatial relationship between the
      inorganic crystals of calcium phosphate and the collagen fibrils of pickerel and
      herring bone. High-voltage stereo electron-micrographs were obtained of cross
      sections of the cylinder-shaped intramuscular bones in uncalcified regions, in
      regions where only one or only several crystals had been deposited in some of the
      fibrils, and in successive sections containing progressively more mineral
      crystals until the stage of full mineralization was reached. High-resolution
      electron probe microanalysis confirmed that the electron-dense particles
      contained calcium and phosphorus. In the earliest stages of mineralization and
      progressing throughout the mineralization process, the crystals are located only
      within the collagen fibrils; crystals are not observed free in the extracellular
      spaces between collagen fibrils. The progressive increase in the mass of mineral
      deposited in the bone tissue with time occurs, essentially, completely within the
      collagen fibrils including the stage of full mineralization. At this stage, cross
      sectional profiles of collagen fibrils are completely obliterated by mineral. A
      small number of crystals that are located on or close to the surface of the
      fibrils appear to extend a very short distance into the spaces between the
      fibrils. These ultrastructural observations of the very onset of calcification in
      which nucleation of the calcium phosphate crystals is clearly shown to begin
      within specific volumes of collagen fibrils, and of the subsequent temporal and
      spatial sequences of this phenomenon, which shows that calcification continues
      wholly within the collagen fibrils until maximum calcification is achieved, add
      important information on the basic physical chemical mechanism of the
      calcification and the structural elements that are involved. The spatial and
      temporal independence of the sites where mineralization is initiated establishes
      that such ultrastructural locations within individual collagen fibrils represent
      independent, physical chemical nucleation loci. The findings are totally
      inconsistent with the proposal that crystals must first be deposited in matrix
      vesicles, or other components such as mitochondria, and subsequently released and
      propagated in the interfibrillar space, until they eventually reach and
      impregnate the hole zone regions of the collagen fibrils. Three-dimensional
      computer reconstruction of serial transverse and longitudinal sections
      demonstrates periodic swellings along the collagen fibrils, corresponding to the
      hole zone region of their axial period as mineralization proceeds.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 1994037
TI  - The refined structure of the complex between adenylate kinase from beef heart
      mitochondrial matrix and its substrate AMP at 1.85 A resolution.
AB  - The crystal structure of the complex between adenylate kinase from bovine
      mitochondrial matrix and its substrate AMP has been refined at 1.85 A resolution
      (1 A = 0.1 nm). Based on 42,519 independent reflections of better than 10 A
      resolution, a final R-factor of 18.9% was obtained with a model obeying standard
      geometry within 0.016 A in bond lengths and 3.2 degrees in bond angles. There are
      two enzyme: substrate complexes in the asymmetric unit, each consisting of 226
      amino acid residues, one AMP and one sulfate ion. A superposition of the two full
      length polypeptides revealed deviations that can be described as small relative
      movements of three domains. Best superpositions of individual domains yielded a
      residual overall root-mean-square deviation of 0.3 A for the backbone atoms and
      0.5 A for the sidechains. The final model contains 381 solvent molecules in the
      asymmetric unit, 2 x 72 = 144 of which occupy corresponding positions in both
      complexes.

PMID- 1994038
TI  - Domain structure and interactions of the type I and type II modules in the
      gelatin-binding region of fibronectin. All six modules are independently folded.
AB  - The gelatin-binding region of fibronectin is isolated easily as a stable and
      functional 42 kDa fragment containing four type I "finger" modules and two type
      II "kringle-like" modules arranged in the order I6-II1-II2-I7-I8-I9. This
      fragment exhibits a single reversible melting transition near 64 degrees C in TBS
      buffer (0.02 M-Tris buffer containing 0.15 M-NaCl, pH 7.4). The transition is
      characterized by a calorimetric to van't Hoff enthalpy ratio of 1.6, suggesting a
      complex domain structure. A 30 kDa fragment with the same NH2 terminus (I6-II1
      II2-I7) melts reversibly near 65 degrees C with delta Hcal/delta HvH = 1.3, also
      consistent with the presence of more than one domain. To elucidate further the
      domain structure, three non-overlapping subfragments were prepared and
      characterized with respect to their unfolding induced by heat and guanidinium
      chloride. The three subfragments, each containing two modules, are designated
      from amino or carboxyl-terminal location as 13 kDa (I6-II1) 16 kDa (II2-I7) and
      21 kDa (I8-I9) according to their apparent Mr in SDS/polyacrylamide gel
      electrophoresis. All three subfragments exhibited reversible transitions in TBS
      buffer, behaving in the calorimeter as single co-operative units with delta
      Hcal/delta HvH close to unity. However, the specific enthalpies and changes in
      heat capacity associated with the melting of all fragments and subfragments in
      TBS buffer were low compared to those of most compact globular proteins,
      suggesting that not all modules are represented. When titrated with guanidinium
      chloride at 25 degrees C, all fragments exhibited monophasic reversible unfolding
      transitions detected by changes in fluorescence. Heating in the presence of 6 M
      guanidinium chloride revealed three additional transitions not seen in the
      absence of denaturants. These transitions have been assigned to three of the four
      type I finger modules (I6, I7 and I9), one of which (I6) was isolated and shown
      to retain a compact structure as stable as that observed for this module within
      the parent fragments. Two other modules (II2 and I7) are destabilized when
      separated from their neighbors. Thus, despite their small size (50 to 60 amino
      acid residues), all six of the modules in the gelatin-binding region of
      fibronectin form independently folded domains, three of which (I6, I7 and I9) are
      unusually stable. Evidence is provided that four of the six modules interact with
      each other in the parent fragment. This interaction may explain previously noted
      disruptions in the otherwise uniform strand-like images seen in electron
      micrographs of fibronectin.

PMID- 1994039
TI  - Postoperative instillation of mitomycin eye drops in the treatment of primary
      pterygium.
AB  - 1. Pterygia, triangular sheets of fibrovascular tissue that invade the cornea,
      have recurrence rates of 30% to 50% with currently available surgical procedures.
      2. Mitomycin, an antimetabolite-antibiotic agent, has been reported to be
      effective in preventing recurrences of surgically excised pterygia when used
      adjunctively as eye drops. 3. Because mitomycin-C is an antineoplastic agent,
      appropriate policies and proper patient education are important.

PMID- 1994040
TI  - Optic nerve meningioma: a case report.
AB  - 1. Primary meningiomas are slow growing, cytologically benign tumors that can
      invade the optic nerve, dura, or extraocular muscles, but do not metastasize. 2.
      Although many of the presenting signs, symptoms, and clinical patterns for
      primary meningioma are nonspecific, there can be a distinctive pattern. 3.
      Treatment depends on the patient's visual acuity, size, and location of the
      tumor.

PMID- 1994041
TI  - Saving costs and enhancing patient care: a solution's solution.
AB  - 1. Although less than 150 mL of a 500 mL bottle of irrigating solution is
      typically used, it is not safe to respike the solution for another patient. 2.
      Presterilized, disposable, multi-use dispensing systems have been used for years
      to compound IV solutions; the same principle can now be used for irrigating
      solutions. 3. The Multi-Spike device can continuously deliver irrigation solution
      through three sterile ports after initial spiking of the solution bottle safely
      and at a lowered cost.

PMID- 1994042
TI  - No greater gift.

PMID- 1994043
TI  - Using our senses.

PMID- 1994044
TI  - Glaucoma High Risk Alert.

PMID- 1994045
TI  - External eye photography using 35 mm camera systems.
AB  - 1. For any close-up photography, a single lens reflex type of camera should be
      used. 2. Magnification of an image can be increased either by lengthening the
      distance between the lens and the film or by adding supplementary lenses. 3.
      Photography of the eye presents special lighting problems, requiring the
      pretesting of exposures, and careful exposure control.

PMID- 1994046
TI  - Is self-examination effective in screening for breast cancer?

PMID- 1994047
TI  - Expression of the nm23 gene and breast cancer prognosis.

PMID- 1994048
TI  - Non-Hodgkin's lymphoma rate climbed rapidly.

PMID- 1994049
TI  - 1971-1991: diagnosis and treatment advances improve survival.

PMID- 1994050
TI  - Clinical announcements: where do we go from here?

PMID- 1994051
TI  - Owens leads effort to promote cancer research.

PMID- 1994052
TI  - Infective dermatitis linked to HTLV-I.

PMID- 1994053
TI  - Colorectal cancer screening.

PMID- 1994054
TI  - Viability of cancer clinical research: patient accrual, coverage, and
      reimbursement. American Medical Association Council on Scientific Affairs.

PMID- 1994055
TI  - Breast self-examination in relation to the occurrence of advanced breast cancer.
AB  - Two hundred nine female enrollees of the Group Health Cooperative of Puget Sound
      who developed advanced-stage breast cancer during the period 1982-1988 were
      interviewed about their practice of breast self-examination (BSE), use of other
      breast cancer screening modalities, and medical and reproductive histories. Each
      subject's description of how she performed the examination was scored according
      to her mention of up to 10 recommended BSE techniques. A random sample of 433
      women without advanced-stage breast cancer from the same population was
      interviewed for comparison. Relative to women not practicing BSE, the risk of
      advanced-stage breast cancer among BSE users was 1.15 (95% confidence interval,
      0.73-1.81). Frequency of BSE did not differ between women with advanced-stage
      breast cancer and control subjects, whether in all subjects or in subgroups
      defined by age, use of mammography, or frequency of clinical breast examinations.
      While self-described proficiency in BSE was generally low in both case and
      control subjects, the small percentage of women reporting more thorough self
      examinations, regardless of frequency, had about a 35% decrease in the occurrence
      of advanced-stage breast cancer compared to women who did not perform BSE. These
      results suggest that, while carefully performed BSE may avoid the development of
      some advanced-stage breast cancers, BSE as practiced by most Seattle-area women
      is of little or no benefit.

PMID- 1994056
TI  - 4-Aminobiphenyl hemoglobin adducts in fetuses exposed to the tobacco smoke
      carcinogen in utero.
AB  - Maternal-fetal exchange of a potent tobacco-related human carcinogen, 4
      aminobiphenyl, was studied in smoking (n = 14) and nonsmoking (n = 38) pregnant
      women. N-Hydroxy-4-aminobiphenyl, the active metabolite of 4-aminobiphenyl, forms
      chemical addition products (adducts) with hemoglobin. Levels of 4-aminobiphenyl
      hemoglobin adducts were measured in maternal-fetal paired blood samples obtained
      from smoking and nonsmoking women during labor and delivery. Carcinogen
      hemoglobin adducts were detected in all maternal and fetal blood samples. Levels
      of such adducts were significantly higher (P less than .001) in maternal and
      fetal blood samples from smokers: the mean 4-aminobiphenyl hemoglobin adduct
      level was 92 +/- 54 pg/g of hemoglobin in blood samples from fetuses of smokers,
      and 17 +/- 13 pg/g of hemoglobin in blood samples from fetuses of nonsmokers; the
      mean maternal 4-aminobiphenyl hemoglobin adduct level was 183 +/- 108 pg/g of
      hemoglobin in smokers, and 22 +/- 8 pg/g of hemoglobin in nonsmokers. Fetal
      carcinogen-adduct levels were consistently lower than maternal levels: the mean
      maternal to fetal ratio was 2.4 +/- 1.1 in smokers and 1.9 +/- .98 in nonsmokers.
      Fetal 4-aminobiphenyl hemoglobin adduct levels were strongly associated
      (correlation coefficient [r2] = .51, P = .002) with maternal 4-aminobiphenyl
      hemoglobin adduct levels when paired samples from smoking mothers were analyzed.
      A measure of third-trimester tobacco smoke exposure based on number of cigarettes
      smoked per day, amount of each cigarette smoked, and depth of inhalation was
      associated (r2 = .59, P = .029) with maternal 4-aminobiphenyl levels but not with
      fetal 4-aminobiphenyl levels. This study demonstrates that a potent tobacco
      related carcinogen, 4-aminobiphenyl, or its active metabolite, N-hydroxy-4
      aminobiphenyl, crosses the human placenta and binds to fetal hemoglobin in
      concentrations that are significantly higher in smokers than in nonsmokers.

PMID- 1994057
TI  - Expression of the antimetastatic gene nm23 in human breast cancer: an association
      with good prognosis.
AB  - The nm23 gene was identified in murine melanoma cells, in which its expression is
      associated with the cells' metastatic potential. Expression of nm23 has been
      detected in human breast tumors by means of hybridization and
      immunocytochemistry. We measured nm23 mRNA in 71 patients with primary breast
      cancer and found variable levels of nm23 expression. The nm23 gene was expressed
      at higher levels in well-differentiated tumors (P less than .02). There was a
      significant inverse relationship between nm23 expression and nodal status (P less
      than .02). Expression of nm23 was positively associated with longer disease-free
      survival and overall survival, and the relationships were significant (P less
      than .002 and P less than .003, respectively). This study showed that nm23
      expression in human breast cancer was associated with good prognosis and a lack
      of lymph node metastasis and suggests that the nm23 gene product may play an
      important role in suppressing the metastatic phenotype.

PMID- 1994058
TI  - Fluorouracil and recombinant human interferon alfa-2a in the treatment of
      metastatic chemotherapy-refractory urothelial tumors.
AB  - Thirty patients with advanced metastatic and chemotherapy-refractory urothelial
      tumors received a combination of fluorouracil (5-FU) and recombinant human
      interferon alfa-2a. Thirty-six sites of metastases were present in the 30 study
      patients, and the median Eastern Cooperative Oncology Group performance status
      was 3 (range, 1 to 4). All patients had failed to respond to primary combined
      methotrexate/cisplatin-based chemotherapy. Nine (30%; confidence interval, 15% to
      47%) of the patients achieved a partial response. The mean duration of response
      was more than 5.2 months (median, 6 months; range, 3 to 8 months). Two patients
      who achieved a partial response of 5 and 7 months' duration, respectively, had
      control of residual disease (one with radiation and one with surgical excision)
      and have remained disease-free for an additional period of more than 7 and 13
      months, respectively. These data suggest that the combination of 5-FU and
      recombinant human interferon alfa-2a is synergistic, with clinical significance
      for the treatment of urothelial tumors. The response rate for this combination of
      drugs is higher than that anticipated for either of these agents used alone.
      Additional confirmatory trials are needed to evaluate the significance of these
      findings.

PMID- 1994059
TI  - Serum selenium level in relation to in situ cervical cancer in Australia.

PMID- 1994060
TI  - Enhancement of mammary carcinogenesis by high levels of dietary fat and its
      association with ad libitum feeding.

PMID- 1994061
TI  - Racial targeting of AIDS programs reconsidered.
AB  - Most health professionals understand the importance of targeting behaviors, not
      groups, for disease prevention. Yet with regard to acquired immune deficiency
      syndrome (AIDS) education programming, target groups have been defined by salient
      demographic traits, including race, in part due to incomplete knowledge about
      risk behaviors in various groups. As a result, community and school-based
      education programs have suffered some mistrust and resentment. This article
      reports the findings of original research on attitude and behavioral differences
      between and within racial groups for a college student sample, in response to
      AIDS education programming. Differences in baseline attitudes and behaviors
      showed that AIDS-related risk cannot be primarily associated with minority group
      status. Implications on refinement of targeting strategies are discussed.

PMID- 1994062
TI  - Anatomy of the thorax and shoulder girdle displayed by magnetic resonance
      imaging.
AB  - In 1971, radiographic anatomy of the human body was added to the gross anatomy
      course at UCLA. Radiographic contrast studies and plain anatomical displays were
      formulated into teaching packages for all organ systems. Residents presented each
      package to first-year medical students in the dissection laboratory to augment
      the teaching of anatomy. In November 1984, magnetic resonance imaging was
      instituted in the radiology department. Imaging the chest produced coronal and
      axial planes which displayed the muscles and soft tissues of the thorax. In 1986,
      the authors presented their study of MR anatomy of the chest and shoulder girdle
      to the American Association of Anatomists. The purpose of this presentation is to
      demonstrate the anatomy of the thorax and shoulder girdle as displayed by
      magnetic resonance, correlated with regional anatomy, with emphasis on soft
      tissue structures.

PMID- 1994063
TI  - Length of human umbilical cords in an African population.
AB  - Six hundred and sixty-one consecutive umbilical cords of babies at term in an
      African obstetric population were studied. The mean cord length was 58.4 +/-
      12.02 cm. The pattern of frequency distribution of cord length in this study
      conforms to previous findings from other racial groups, establishing the fact
      that cord length and its variability are not racially determined. There is a
      significant correlation between the cord length and weights of the fetus and
      placenta but not with the mother's parity.

PMID- 1994064
TI  - Injury: a new perspective on an old problem.
AB  - Injury-related morbidity and mortality have finally been acknowledged as major
      public health issues facing this country today. While injuries represent a
      serious problem for society as a whole, the rates are significantly higher among
      African-Americans, especially black males between 20 and 29 years of age.
      Moreover, injury and death resulting from acts of interpersonal violence are not
      only increasing, but are also significantly higher among blacks. Because injury
      producing events have been shown to conform to the same biological laws that
      govern the expression and behavior of many infectious and chronic diseases, it
      has now been determined and verified that such events are largely predictable,
      and, in many instances, preventable. Because of the significant racial disparity
      in the incidence of injury-producing events, the authors encourage establishment
      of vigorous injury prevention, control-oriented curricula, and training
      opportunities in predominantly black medical schools. The authors assert that
      such institutions of higher learning represent an ideal point of introduction for
      innovative injury prevention and control strategies specifically aimed at the
      African-American population.

PMID- 1994066
TI  - An analysis of tetanus deaths in Lagos.
AB  - Between 1974 and 1984, 418 patients with tetanus, aged 10 years and older,
      represented 64.8% of all admissions to the intensive care unit of the Lagos
      University Teaching Hospital. Students accounted for the largest single group
      with tetanus, which mainly occurred during the dry season. There was a male
      preponderance (1.4 to 1), but no appreciable sex influence on mortality rates
      (46.1% for men; 44.6% for women). The mean mortality rate was 45.5%, with the
      highest mortality occurring in the elderly. Other high risk factors identified
      were neck and head injuries, post abortal or post partum states, hyperpyrexia,
      and tachycardia.

PMID- 1994065
TI  - Left ventricular diastolic dysfunction in patients with congestive heart failure.
AB  - This study reviewed 372 male patients with congestive heart failure. Two hundred
      and eighty-three (77%) had congestive heart failure due to systolic dysfunction
      as demonstrated by radionuclide angiography. Eighty-seven (23%) with congestive
      heart failure were identified who had normal ejection fractions. All patients met
      the Framingham criteria for congestive heart failure. These 87 individuals had
      unrecognized diastolic heart failure. It is important to distinguish between
      systolic and diastolic heart failure because the pathophysiology, treatment, and
      prognosis differ significantly. The most frequent cause of diastolic heart
      failure in this study was hypertension. Diastolic dysfunction should be
      considered in patients with acute heart failure and severe uncontrolled
      hypertension, or in patients with ischemic heart disease who develop acute
      pulmonary edema. Patients who do not respond or deteriorate when treated for
      heart failure using conventional therapy may also have diastolic dysfunction.
      These patients warrant special recognition and tailored management.

PMID- 1994067
TI  - Radiological evaluation of the pancreas in malnutrition-related (phasic insulin
      dependent) diabetes mellitus.
AB  - This study was undertaken to investigate pancreatic changes associated with
      phasic insulin dependent diabetes mellitus (PIDDM). Twelve PIDDM patients were
      studied. They were compared with groups of patients, 10 insulin dependent (IDDM),
      10 non-insulin dependent (NIDDM), and 10 normal controls. Each group was matched
      for age, sex, and body mass index. For the study, the mean age was 56.7 +/- 2.5
      years, mean body mass index 24.0 +/- 0.8, and mean duration of diabetes 14.2 +/-
      2.2 years. Flat abdominal radiograph and ultrasonography were performed on each
      participant. The results suggest an increased echogenicity of the pancreas in the
      phasic insulin dependent group of patients.

PMID- 1994068
TI  - Musculoskeletal disorders in female veterans: a survey.
AB  - This study discusses age distribution, outpatient clinic visits, and diagnoses of
      female veterans with trauma-related musculoskeletal conditions. From 1981 to
      1988, data were collected of female veterans seen for treatment or examination of
      compensation awards. Their prevalent musculoskeletal disorders were of the back,
      feet, and knees. This study served as a means of preparation for the anticipated
      changing needs of these patients when ambulatory.

PMID- 1994069
TI  - Late arterial erosion of a Crutchfield vascular clamp presenting with transient
      ischemic attacks: review of treatment options.
AB  - Crutchfield clamps were once widely used for proximal carotid artery ligation in
      the treatment of intracranial aneurysms and cavernous sinus fistulae.
      Consequently, there are a number of patients being followed who were treated with
      this device 10 to 15 years ago. The most important complication of this treatment
      modality in both the early and late postoperative period is thromboembolic
      phenomenon presenting as transient ischemic attacks, or a frank stroke. Because
      of the residual patient population with this device still in place, interval
      reports regarding the occurrence and treatment of late complications are
      important. We report a patient who underwent Crutchfield clamp application for
      control of a cavernous sinus fistula and had done well for 20 years when he
      developed transient ischemic attacks (TIA). Arteriography revealed a severe
      stenotic lesion (greater than 90%) in the common carotid artery with a patent
      internal carotid artery and no evidence of the previous fistula and an ulcerated
      plaque. At surgery, the pressure plate of the clamp had achieved an intraluminal
      position. The stenotic area was resected and an end to end anastomosis performed
      with complete resolution of symptoms after 18 months of follow-up. In this report
      we review the literature for complications of this device and discuss treatment
      options.

PMID- 1994070
TI  - Propylthiouracil-associated hepatitis.
AB  - The case of a 43-year-old female with propylthiouracil-induced hepatitis is
      reported. The case is unique because the patient's liver function deteriorated 2
      weeks after medication was discontinued.

PMID- 1994071
TI  - Dupuytren's contracture and gouty tophi in a black patient.
AB  - Dupuytren's disease is a relatively rare occurrence in a patient of the black
      race. The coexistence of a Dupuytren's contracture in a black patient who also
      presents with severe gouty tophi is described. This is the first reported case in
      the English literature.

PMID- 1994072
TI  - Parosteal osteosarcoma of the distal tibia.
AB  - We report on the case of a 24-year-old black male who presented to the orthopedic
      service with a parosteal osteosarcoma of the distal tibia. There have been 206
      cases reported on this tumor in all the world's literature, with the distal femur
      being the most common location; this case report is rare, therefore, because of
      the unusual location of the tumor. This article was prepared in order to
      familiarize the general medical community with the occurrence of the tumor and to
      provide some general background information and treatment recommendations for
      parosteal osteosarcoma.

PMID- 1994073
TI  - Sphenoid sinusitis.
AB  - Significant morbidity and mortality can result if early detection and treatment
      of sphenoid sinusitis is not provided. A case is presented in which the diagnosis
      of sphenoid sinusitis was delayed because a routine computerized tomographic scan
      was normal. This case underscores the importance of specifically requesting views
      of the paranasal sinuses in suspected cases of sinusitis.

PMID- 1994075
TI  - Blunt traumatic rupture of the heart and pericardium: a ten-year experience (1979
      1989).
AB  - Blunt traumatic rupture of the heart and pericardium, rarely diagnosed
      preoperatively, carries a high mortality rate. From 1979 to 1989, more than
      20,000 patients were admitted to a Level I trauma center. A retrospective review
      identified 59 patients requiring emergency surgery for this condition. Injuries
      resulted from vehicular accidents (68%), motorcycle crashes (10%), pedestrians
      being struck by vehicles (7%), falls (5%), crushing (7%), and being struck by a
      horse (2%) or crane (2%). Seventeen patients (29%) had isolated rupture of the
      pericardium; 37 (63%) had ruptures of one or more cardiac chambers. All patients
      had signs of life at the scene or during transportation, but only 29 (49%) had
      vital signs on admission: 15 with chamber injury, 12 with pericardial rupture,
      and two with combined injuries. Diagnosis was established by emergency
      thoracotomy in the 30 patients who arrived in cardiac arrest. In the remaining 29
      patients, diagnosis was made by urgent thoracotomy (41%), by subxiphoid
      pericardial window (34%), during laparotomy (21%), or by chest radiography (3%).
      The overall mortality rate was 76% (45 patients), but only 52% for those with
      vital signs on admission. Rapid transportation and expeditious surgical treatment
      can save many patients with these injuries.

PMID- 1994074
TI  - Ibuprofen prevents deterioration in static transpulmonary compliance and
      transalveolar protein flux in septic porcine acute lung injury.
AB  - The effects of intravenous ibuprofen on measurements of pulmonary function and
      alveolar capillary membrane permeability to protein in sepsis-induced porcine
      acute lung injury (ALI) were studied. Young swine (15-25 kg) were anesthetized,
      cannulated, and ventilated (5 cm H2O PEEP, 0.5 FIO2, and 15 cc/kg tidal volume).
      Three groups were studied: septic animals (Ps, n = 10) received Pseudomonas
      aeruginosa for 1 hr IV, controls (C, n = 9) received 0.9% NaCl, and ibuprofen
      treated septic animals (Ps + Ibu, n = 7) received ibuprofen 12.5 mg/kg at 0 and
      120 min post Ps. Systemic (SAP) and pulmonary (PAP) arterial pressures, PaO2,
      cardiac index (CI), static lung compliance (CL), EVLW (thermal cardiogreen), and
      peripheral white blood cell counts (WBC) were measured. Bronchoalveolar lavage
      (BAL) was performed for protein and % neutrophil (%PMN) content. RESULTS: Ps
      produced significant (p less than 0.05) decreases in CL, PaO2, SAP, CI, and
      peripheral WBC and increases in PAP, EVLW, BAL protein, and %PMN's vs. controls.
      Ibu prevented the early increase in PAP and attenuated the late increase in PAP
      and EVLW. Ibu also maintained PaO2, CL, BAL protein, and %PMN's in BAL at control
      levels, but exhibited no significant effect on peripheral leukopenia. These data
      strongly suggest that ibuprofen administered before and at 120 min after onset of
      Pseudomonas infusion improves lung compliance and affects neutrophil function
      sufficiently to significantly ameliorate many of the physiologic derangements in
      acute sepsis.

PMID- 1994076
TI  - The rat lung organotypic culture: an in vitro model for studying surfactant
      metabolism abnormalities.
AB  - The amount of surfactant present in the intra-alveolar space is mainly regulated
      by the synthesis and recycling of surfactant by type II pneumocytes. Biochemical
      analyses have shown that the surfactant level is frequently diminished and that
      protein-rich exudate can further interfere with surfactant function in the lungs
      of adult respiratory distress syndrome (ARDS) patients. The microenvironmental
      changes that occur in the alveoli of burned patients, who are prone to developing
      ARDS, are unclear. Therefore, using an in vitro rat lung organotypic culture, we
      showed that the sera of rats with a 3-day old, third-degree thermal injury (25
      30% total body surface area) inhibited surfactant synthesis in organotypically
      cultured rat lung cells. Surfactant precursor, 3H-choline, incorporation into the
      surfactant was 58% of control. Using liposomes made of dipalmitoyl
      phosphatidylcholine and phosphatidylglycerol (8:1, v/v) or surfactant we showed
      that surfactant endocytosis by purified type II alveolar cells is an active,
      temperature-dependent process, and correlates with the quantity of surfactant
      present in the milieu. We also found that plasma protein-rich fluid interfered
      with surfactant endocytosis by the purified type II pneumocytes. These two
      processes of inhibition of surfactant synthesis and its reutilization by these
      cells may contribute to the pathogenesis of ARDS.

PMID- 1994077
TI  - Combined hemorrhagic shock and head injury: effects of hypertonic saline (7.5%)
      resuscitation.
AB  - Hypertonic saline resuscitation was compared to isotonic fluid resuscitation in a
      large animal model combining hemorrhagic shock with head injury. Sheep were
      subjected to a freeze injury of one cerebral hemisphere as well as 2 hours of
      hypotension at a mean arterial pressure (MAP) of 40 mm Hg. Resuscitation was then
      carried out (MAP = 80 mm Hg) for 1 hour with either lactated Ringer's (LR, n = 6)
      or 7.5% hypertonic saline (HS, n = 6). Hemodynamic parameters and intracranial
      pressure (ICP) were followed. At the end of resuscitation brain water content was
      determined in injured and uninjured hemispheres. No differences were detected in
      cardiovascular parameters; however, ICPs were lower in animals resuscitated with
      HS (4.2 +/- 1.5 mm Hg) compared to LR (15.2 +/- 2.2 mm Hg, p less than 0.05).
      Additionally, brain water content (ml H2O/gm dry weight) in uninjured brain
      hemispheres was lower after HS resuscitation (HS = 3.3 +/- 0.1; LR = 4.0 +/- 0.1;
      p less than 0.05). No differences were detected in the injured hemispheres. We
      conclude that hypertonic saline abolishes increases in ICP seen during
      resuscitation in a model combining hemorrhagic shock with brain injury by
      dehydrating areas where the blood-brain barrier is still intact. Hypertonic
      saline may prove useful in the early management of multiple trauma patients.

PMID- 1994078
TI  - Splenectomy does not influence outcome of pneumococcal septicemia in a porcine
      model.
AB  - The existence of the overwhelming postsplenectomy infection syndrome in adults
      after traumatic splenectomy is controversial. Due to the similarity of the
      porcine immune system to man we chose the pig to study subsets of peripheral
      mononuclear cells after splenectomy and resistance to experimental Pneumococcal
      infection after splenic surgery and specific immunization. Female miniature pigs
      were assigned to four operative groups: sham operation, splenectomy, splenic
      resection, and heterotopic splenic autotransplantation. Hematologic and flow
      cytometric analysis of mononuclear cells and their subsets revealed a marked
      leukocytosis following splenectomy and autotransplantation but no significant
      shift in monocyte and B-cell numbers. Response of leukocytes to septicemia,
      bacterial elimination from peripheral blood, and mortality were not affected by
      splenectomy or spleen-preserving operations. Mortality of splenectomized animals
      was 18%, compared to 42% in sham-operated controls (difference not significant).
      Immunization protected animals from development of leukopenia, and led to an
      enhanced bacterial elimination, and a significantly decreased mortality of 5%,
      compared to 48% in nonimmune animals. Thus our data do not show significant
      effects of splenectomy on subsets of porcine mononuclear cells or on resistance
      to experimental Pneumococcal septicemia.

PMID- 1994079
TI  - Functional outcome of pediatric trauma patients identified as 'non-salvageable
      survivors'.
AB  - A retrospective study of 305 pediatric trauma patients seen over 17 months was
      undertaken to evaluate the functional outcome of patients categorized as "non
      salvageable survivors" (NSS). Functional outcome was determined by Denver
      Developmental Screen Tests (DDST) for children less than 5 years of age and
      Rappaport Severity Rating Scale (RDRS) for those 5 years old and older. Each
      patient was assigned Abbreviated Injury Scores (AIS). Injury Severity Score
      (ISS), Glasgow Coma Scale (GCS), and Trauma Score (TS). The total number of
      patients classified as severe was 65 (21%), and 13 were classified as non
      salvageable, with seven non-salvageable survivors and six non-preventable deaths.
      Our study suggests that current trauma scoring systems tend to overestimate the
      non-salvageable population. Those identified as non-salvageable and who survived
      have a high probability of meaningful functional recovery. Current trauma scoring
      systems are in need of revision to better identify non-salvageable survivors and
      those children who will not make a meaningful neurologic recovery.

PMID- 1994080
TI  - Optimal escort for interhospital transport of pediatric emergencies.
AB  - The charts of 130 seriously ill or injured children transported to tertiary level
      intensive care were examined to determine the incidence of secondary insults
      incurred, as a function of escort training. Of all insults incurred,
      approximately 8% occurred with specialized pediatric transport escorts who were
      accompanied by a tertiary care physician (Group III, n = 52); 20% with
      specialized pediatric transport escorts alone (Group II, n = 44); and 72% with
      escorts who had not received specialized pediatric transport training (Group I, n
      = 34). Based on our results, we recommend that all transport coordinators review
      the qualifications and experience of their transport team members and all
      potential escorts to assess their ability to provide optimal care for the
      children they transport, particularly during long journeys, transfer by air, and
      when serious illness or injury is involved.

PMID- 1994081
TI  - Relative effects of brain and non-brain injuries on neuropsychological and
      psychosocial outcome.
AB  - Based on the 242 consecutive surviving head injury cases and 132 general trauma
      cases, this study examined the contribution of brain and non-brain injuries to
      cognitive and psychosocial outcome 1 month postinjury. The study also examined
      the relationships among various head injury severity indices. The head injury
      severity indices were all correlated but patients with Glasgow Coma Scale scores
      in the mild range had broadly ranging scores on the other head injury severity
      indices (Abbreviated Injury Scale and time to follow commands).
      Neuropsychological outcome was related to brain injury severity, but was not
      independently influenced by severity of other systems injuries. Psychosocial
      outcome related to both brain and non-brain injuries independently. When
      evaluating trauma outcome, it is important to consider the contributions of both
      brain and other system injuries.

PMID- 1994082
TI  - Application of a new positioning device for isometric replacement in anterior
      cruciate ligament repair and reconstruction.
AB  - The functional effects of displacing the cruciate ligament attachments were
      studied in ten adult cadaver knees. On a systematic variation of the femoral and
      tibial attachment sites according to a three-dimensional raster scheme, a
      quantitative analysis of the absolute length and of motion-dependent changes in
      ligament isometry was performed. All insertion points deviating from the original
      anatomic landmarks did not accomplish biomechanical requirements. A femoral
      displacement had an increased effect on disturbing isometry compared to a tibial
      malposition. Although recommended by several authors, the "over-the-top" position
      gave the most unsatisfactory results with a maximum isometry failure of 10 mm. In
      cruciate ligament replacement a positioning guide with isometry testing capacity
      should be mandatory to ensure correct placement of bone tunnels. For this purpose
      a new positioning device which allows for isometry measurements before a bone
      channel is drilled is introduced and applied in an experimental setup.

PMID- 1994083
TI  - Humeral mobility after treatment with hanging cast.
AB  - A retrospective review of 23 patients after treatment of humeral fractures with
      hanging cast was performed. The average followup time was 8.59 years (range, 1.0
      to 15.5 years). Functional results were good in eight (34.8%) and excellent in 15
      patients (65.2%). To assess the flexibility of shoulder and elbow joints 24
      parameters were measured on each body side using the neutral-zero method of
      Debrunner. A cumulative comparison of each parameter revealed decreased
      flexibilities of the upper limb after treatment with hanging cast: reduced
      abduction without moving shoulder blade (84.08 +/- 7.53 vs. 77.34 +/- 11.38; p
      less than 0.05), reduced free abduction (166.09 +/- 14.4 vs. 158.22 +/- 19.28; p
      less than 0.01), reduced anteelevation (155.26 +/- 10.12 vs. 149.35 +/- 3.22; p
      less than 0.01), reduced external rotation with hanging arm (48.96 +/- 19.05 vs.
      41.18 +/- 16.75; p less than 0.01), increased flexion of the shoulder (25.65 +/-
      10.37 vs 27.3 +/- 10.0; p less than 0.05) and reduced extension of the elbow
      (0.86 +/- 6.92 vs. -2.68 +/- 9.63; p less than 0.05). These findings show that
      longterm deficiencies of humeral mobility after treatment with hanging casts
      exist.

PMID- 1994084
TI  - Results of operative treatment for intra-articular fractures of the calcaneus.
AB  - Since 1980 our treatment of displaced intra-articular calcaneal fractures
      consists of open reduction with distractor, bone grafting, and internal fixation.
      Thereby no splints are applied and early postoperative movement is possible. For
      precise preoperative planning a CT scan is required. Proper timing and careful
      preoperative planning are essential to prevent soft-tissue complications. In a
      total of 16 fractures good clinical and radiologic results were achieved in 50%
      of the cases; results were satisfactory in 25% and poor in 25%. The patients
      returned to work after an average of 5 months. Only three patients (19%) received
      disability compensations, which compares favorably with nonoperative treatment.
      We believe that a majority of comminuted intra-articular fractures of the
      calcaneus profit from open reduction and internal fixation and that more reliable
      functional results are achieved than with conservative therapy.

PMID- 1994085
TI  - Sonographic screening of mass casualties for abdominal and renal injuries
      following the 1988 Armenian earthquake.
AB  - The value of sonography in acute trauma evaluation is generally underestimated,
      and the opinions are controversial. Sonography was performed as a primary
      screening procedure in 400 of 750 mass casualty patients with trauma admitted to
      a large hospital within the first 72 hours after the 1988 Armenian earthquake.
      Two real-time sector scanners were used in the reception area of the hospital,
      and the average time spent on one patient was 4 minutes. More than 130 followup
      sonographic examinations were required. Trauma-associated pathology of the
      abdomen and retroperitoneal space was detected in 12.8% of the patients, with 1%
      false negatives and no false positives. The authors believe that sonographic
      screening of mass casualties is a quick and effective means for detection of
      abdominal and retroperitoneal injuries. Sonography should be used for this
      purpose more routinely to gain experience and maintain preparedness of the
      sonographers for screening of trauma cases in mass casualty situations.

PMID- 1994086
TI  - Morbidity and mortality in the martial arts: a warning.
AB  - Approximately 1.5 to 2 million Americans participate in the martial arts. Injury
      anecdotes are reported from 10 years of providing medical coverage at martial
      arts activities. Included are data from two national Tae Kwon Do tournaments, one
      adult and one junior level. Previously unreported injuries, including a video
      recorded fatality, demonstrate the danger inherent in participation. Of
      particular concern is the potential for serious neurologic injury.
      Recommendations are made for reducing the severity and frequency of injuries.

PMID- 1994087
TI  - Computed tomography in the evaluation of the aorta in patients sustaining blunt
      chest trauma.
AB  - Computed tomography is used with increasing frequency to evaluate blunt chest
      trauma. Since traumatic aortic rupture (TAR) is a rapidly lethal condition,
      unnecessary CT scanning may not be justified. To determine the accuracy of chest
      CT scanning for TAR, we reviewed 17 patients who underwent both chest CT scanning
      and aortography. Five patients had TAR by aortography. CT scanning yielded three
      true positives and two false negatives. In 12 patients with a negative aortogram,
      CT scanning recorded four false positives and eight true negatives. The
      specificity was 23% and the sensitivity was 83% compared with aortography. The
      overall accuracy for CT scanning was 53%. From these data we conclude that in the
      presence of an unstable patient or where there is a strong clinical suspicion of
      TAR the patient should proceed directly to aortography.

PMID- 1994088
TI  - Delayed diagnosis of extremity injuries in patients with multiple injuries.
AB  - A total of 340 patients treated in the Intensive Care Unit of the Department of
      Orthopedics and Traumatology at Helsinki University Central Hospital were
      analyzed in this study. They had in all 1,071 fractures and luxations of the
      pelvis and extremities, of which the trauma surgeons and radiologists on duty
      initially missed 45 injuries, i.e., 4.2%. Taking into account the eventual late
      symptoms, the most severe delayed diagnoses were of injuries located around the
      hip and knee joints. The patients with delayed diagnoses were, on the average,
      the most severely ill: their needs for primary blood transfusions and assisted
      respiration resembled the needs of patients who later died of their trauma or its
      complications. The most common causes of the delay in diagnosis were: radiographs
      not done in 60% of patients, and no notation of visible injury in radiographs in
      31%. Inferior quality of radiographs, unnoticed radiologists' reports, a fracture
      visible at the outermost corner of a radiograph, a fracture hidden by other
      fractures, or excessive obesity of the patient may also contribute to a delay.
      The study presents measures for improving diagnostic strategies, but it would
      appear that delayed diagnoses cannot be totally eradicated.

PMID- 1994089
TI  - Timing of osteosynthesis of major fractures in patients with severe brain injury.
AB  - A retrospective study was performed to assess the effects on outcome of early
      osteosynthesis of major extremity fractures in patients with severe brain injury
      (GCS less than or equal to 7). In a consecutive series of 58 patients, early
      osteosynthesis was performed on the day of injury in 15 patients. (Group A). In
      43 patients no major fractures were present or no early osteosynthesis was
      performed (Group B). The severity of brain injury as seen on CT scan was similar
      in both groups. Mortality was significantly lower in Group A, despite a
      significantly higher ISS. As to the functional end result of brain injury, an
      indication of a better outcome was present in Group A.

PMID- 1994090
TI  - Successful replantation of both legs in a child--5-year followup: case report.
AB  - Replantation of lower extremities is an infrequent procedure, and is rarely
      indicated, due to the usual severity of the primary injury plus the possibility
      of good prosthetic substitution. We report a case of successful replantation of
      both legs in an 8-year-old boy (despite Aspergillus flavus septicemia) with
      followup of 5 years. This case suggests that leg replantation should be
      considered in young patients. This appears to be the second reported case of
      successful replantation of both legs.

PMID- 1994091
TI  - Isolated hyoid bone fracture: a case report and review of the literature.
AB  - Isolated hyoid bone fractures secondary to trauma other than strangulation are
      rare and have few, if any, complications. We report a case of an isolated hyoid
      bone fracture that resulted in sudden and severe upper airway compromise.
      Diagnosis of these fractures is difficult and usually can be made only with a
      strong degree of suspicion. Patients who suffer neck injuries in whom a hyoid
      fracture is diagnosed or strongly suspected should be observed for 48 to 72
      hours, considered for endoscopy, and treated as warranted.

PMID- 1994092
TI  - Ossified chronic subdural hematoma: case report.
AB  - A case of ossified chronic subdural hematoma is presented in a 13-year-old male
      in whom the mass was surgically removed. His neurological deficits continued
      afterward but were less severe.

PMID- 1994093
TI  - Reflex sympathetic dystrophy after clavicle fracture: case report.
AB  - Reflex sympathetic dystrophy (RSD) of the anterior chest wall is a rare entity. A
      MEDLINE search in all languages of the world's literature from 1966 to the
      present yielded no report of the association of clavicle fracture with this pain
      syndrome. Two cases are presented and the anatomic variations of the
      supraclavicular nerves in relation to the clavicle are discussed.

PMID- 1994094
TI  - Spontaneous healing of a traumatic thoracic aortic tear: case report.
AB  - A patient with deceleration trauma of the thoracic aorta causing significant
      intimal disruption is described in whom complete angiographic resolution was
      documented during a period of medical management. Review of the literature, along
      with our experience, suggests that traumatic aortic disruption constitutes a
      spectrum of injury rather than an all-or-none phenomenon. Immediate surgery,
      especially in multiply injured patients, may be delayed or even postponed
      indefinitely if the injury is relatively limited.

PMID- 1994095
TI  - Pathologic fracture through a solitary enchondroma of the radial diaphysis: case
      report.
AB  - Solitary enchondromata are rare but well recognised benign bone tumours. They are
      extremely rare in the radius. We report the case of a pathologic fracture through
      a solitary enchondroma in the radial diaphysis and its successful treatment.

PMID- 1994096
TI  - Thoracoabdominal repair of a post-traumatic aortorenal vein fistula following a
      previous transabdominal attempt: case report.
AB  - Aortorenal vein fistula from trauma is a rare entity. A case is reported in which
      previous anterior abdominal attempts at repair rendered a thoracoabdominal
      approach necessary. Previous reports and techniques are compared and discussed.

PMID- 1994098
TI  - Intracranial bullet migration--a sign of brain abscess: case report.
AB  - An unusual case of migration of an intracranial bullet fragment within a brain
      abscess is reported. Movement of the bullet was first detected on skull films,
      and the significance of this finding on plain radiographs is emphasized.

PMID- 1994097
TI  - Hepatic portal venous gas identified by computed tomography in a patient with
      blunt abdominal trauma: a case report.
AB  - An abdominal computed tomographic (CT) scan in a middle-aged man injured in a
      high-speed motor vehicle accident demonstrated the presence of portal venous gas.
      Findings on initial peritoneal lavage were entirely negative. Exploratory
      celiotomy performed because of increasing abdominal pain and leukocytosis
      revealed gangrene of the cecum. This report illustrates the importance of the
      finding of portal venous gas on CT scan in patients with blunt abdominal trauma.

PMID- 1994099
TI  - The role of computerized tomography in the diagnosis of an occult femoral neck
      fracture associated with an ipsilateral femoral shaft fracture: case report.
AB  - We report a nondisplaced femoral neck and head fracture diagnosed acutely by CT
      scanning. This case illustrates the potential benefits of an acute femoral
      neck/head CT scan in obtunded polytrauma patients with high-energy femoral shaft
      fractures.

PMID- 1994100
TI  - Bilateral fracture-dislocation of the sacroiliac joint: a case report.
AB  - Bilateral fracture-dislocation of the sacroiliac joint with intrapelvic
      displacement of the sacrum is a rare and extremely severe injury. We treated a
      patient with bilateral fracture-dislocation of the sacroiliac joint using a
      nonoperative method and obtained an excellent functional result.

PMID- 1994101
TI  - Traumatic renal avulsion into the chest: case report.
AB  - This is a case report of a patient who survived blunt renal avulsion and
      herniation of the kidney through a ruptured diaphragm. Symptoms were mild
      considering the severity of injury. Prompt diagnosis of this unusual combination
      of injuries was aided by contrast-enhanced computed tomography (CT).

PMID- 1994102
TI  - Endoscopic guided percutaneous tracheostomy: early results of a consecutive
      trial.

PMID- 1994103
TI  - [Aggression in residents of homes for the aged].

PMID- 1994104
TI  - [Aggressive nurses].

PMID- 1994105
TI  - [To deal constructively with aggression].

PMID- 1994106
TI  - [Aggression in the emergency service].

PMID- 1994107
TI  - [Verbal intervention].

PMID- 1994108
TI  - [Study on the burnout syndrome. Burnout nurses don't provide warmth].

PMID- 1994109
TI  - [HMO: a promising alternative health insurance. A model of integrated medicine].

PMID- 1994110
TI  - [Conditions and organization of work in an operating room in the canton of
      Neufchatel. Report of an experience].

PMID- 1994111
TI  - [Psychiatric nurse: professional risks].

PMID- 1994112
TI  - [Psychiatric nursing in prison. Hard to obtain the objectives...].

PMID- 1994113
TI  - [Implantable systems for the treatment of cancer--ambulatory chemotherapy: an
      advantage for the patient].

PMID- 1994114
TI  - [New post-diploma education at La Source. Interdisciplinary aspects in
      gerontology-geriatrics].

PMID- 1994116
TI  - [Ethical principles for nursing care].

PMID- 1994115
TI  - [3-week service in a pediatric hospital: development of care from nothing].

PMID- 1994117
TI  - Educational status and drinking patterns: how representative are college
      students?
AB  - Using data from a large, nationally representative sample, multiple regressions
      using sex, ethnicity, age and educational status showed that drinking patterns of
      college students differed significantly from those of dropouts, high school
      graduates and former college students. College students were more likely to use
      alcohol but tended to drink less quantity per drinking day than nonstudents of
      the same age. Sex differences were smaller among college students than among
      other groups, especially in proportions of abstainers. While whites were most
      likely to drink if they were in college, among blacks the college students were
      the least likely to drink. Age had little association with drinking. Conclusions
      based on in-school samples may not generalize well to nonschool populations and
      should be tested, if possible, using more representative databases.

PMID- 1994118
TI  - Associations between alcohol and cocaine use in a sample of problem-drinking
      employees.
AB  - Increases in cocaine use have created a new and challenging cohort of problem
      drinkers with dual or multiple addictions. As part of a randomized trial
      comparing alternative alcoholism treatments at a 10,000-employee industrial
      plant, we interviewed 224 new alcoholic clients of an employee assistance program
      (EAP); 40% used cocaine during the 6 months just prior to EAP intake. Compared to
      employees reporting no recent cocaine use, the cocaine users were younger, less
      often married and reported heavier drinking and more alcohol-related problems, on
      the job and off. Even after controlling for demographic and occupational factors,
      and drinking indicators, cocaine users reported more binges (being drunk 24 hours
      or more), more blackouts (marginally significant, p = .06), more absenteeism and
      more warnings about unacceptable job performance. Alcoholic EAP clients who use
      cocaine appear to engage in riskier drinking and to have more trouble on the job
      than do those who report no cocaine use, and this seems to be a difference
      specifically attributable to their use of cocaine.

PMID- 1994119
TI  - Sex differences in personality traits and coping styles of hospitalized
      alcoholics.
AB  - Forty inpatients on an alcohol detoxication unit of a large municipal hospital
      were administered a battery of tests consisting of a Coping Styles scale, a
      Personality Profile scale, a Depression scale and the Brief MAST. A
      demographically comparable comparison group of 40 outpatients attending the
      medical screening clinic at the same hospital also completed the battery. The two
      groups did not differ in terms of age, education or the ratio of men to women.
      There were significant differences in coping styles and personality
      characteristics between alcoholics and nonalcoholics and, to a large extent,
      between men and women within the alcoholic group. Practically no significant
      differences were found between the men in the two groups, but female alcoholics
      differed greatly from nonalcoholic women in terms of coping styles, personality
      variables and also in terms of conflict. These findings indicate that the
      differences between alcoholic and nonalcoholics in the sample were due largely to
      patterns uniquely characterizing the female alcoholic group. Results are
      discussed in terms of cultural expectations.

PMID- 1994120
TI  - The effectiveness of alcoholism screening in an ambulatory care setting.
AB  - Two hundred and eighty subjects in three ambulatory care clinics participated in
      this study designed to assess the psychometric properties of the SMAST using DSM
      III criteria for alcoholism as the diagnostic standard. Eighty-two subjects (30%)
      who completed the NIMH Diagnostic Interview Schedule met DSM-III criteria for
      alcohol abuse and/or dependence. The sensitivity of the SMAST, using the
      generally accepted weighted cut-off score of five or greater, was .56 and the
      specificity was .83. An unweighted cut-off score of two or greater produced a
      sensitivity of .72 and a specificity of .64. The results of this study suggest
      that, when the SMAST is used for screening in an ambulatory care clinic
      population, the optimum balance of sensitivity and specificity is achieved using
      an unweighted cut-off score of two or greater. In addition, the alcohol subscale
      of the Diagnostic Interview Schedule was easy to administer and should be
      considered for use as the diagnostic standard in clinical settings.

PMID- 1994121
TI  - Patient factors predicting early alcohol-related readmissions for alcoholics:
      role of alcoholism severity and psychiatric co-morbidity.
AB  - The current study was undertaken primarily to identify whether psychiatric co
      morbidity was associated with the rate and time of alcohol-related inpatient
      readmissions for a group of 255 patients discharged from alcoholism treatment at
      a midwestern rural medical center. A structured interview obtained information
      regarding psychiatric disorders, including depression, antisocial personality
      disorders and polysubstance abuse, as well as alcohol history and
      sociodemographics. Ninety-eight subjects (38.4% of sample) were readmitted for
      alcoholism-related diagnoses within 15 months of discharge. Patients with a long
      history of heavy drinking, high daily alcohol consumption and history of previous
      alcoholism treatment were most likely to be readmitted with an alcoholism-related
      primary diagnosis. Once these variables were controlled for, other major
      psychiatric disorders, polysubstances abuse and sociodemographic variables did
      not appear to predict time to readmission. However, other potentially more
      sensitive outcome measures such as return to drinking were not evaluated in the
      present study.

PMID- 1994122
TI  - The long-term course of treated alcoholism: I. Mortality, relapse and remission
      rates and comparisons with community controls.
AB  - This study examines the course of alcoholism for a sample of patients who were
      followed 2 years and 10 years later after an index residential treatment episode.
      The alcoholic patients were 9.5 times as likely to die as matched community
      controls over the 8-year interval between the two follow-ups, a ratio
      considerably higher than that found in previous studies. Of the 83 surviving and
      successfully followed patients, 57% were classified as remitted at the 10-year
      follow-up. Of the patients classified as remitted at the 2-year follow-up and
      recontacted 8 years later, 77% had the same outcome status at the long-term
      follow-up, 67% of the initially relapsed patients retained that status at the 10
      year follow-up. The 10-year remitted patients generally were functioning as well
      as matched, nonproblem-drinking community controls, whereas the relapsed patients
      exhibited dysfunction in a number of areas. Retrospective data on drinking
      patterns during each of the 6 years prior to the 10-year follow-up indicated a
      slight increase over time in the proportion of patients reporting abstinence or
      nonproblem drinking, with a concomitant decrease in the proportion indicating
      heavy or binge drinking. Overall, our data show a substantially elevated
      mortality risk among these alcoholic patients. For those patients who survive,
      however, the average course is one of modest improvement.

PMID- 1994123
TI  - Factors associated with alcohol use in later adolescence.
AB  - The relative influence of a number of family and individual characteristics on
      the frequency and intensity of alcohol use in a group of older adolescents was
      assessed. The sample consisted of 8,661 persons ranging in age from 20 to 21
      years obtained from the "High School and Beyond" study. Logistic regression
      analyses performed on both frequency and intensity of alcohol use indicated that
      white males from higher socioeconomic backgrounds, living in urban or suburban
      areas and having an external locus of control and a weak family orientation,
      tended to drink more frequently and consume a larger quantity of alcohol per
      drinking episode. Results are explained from a sociocultural perspective.

PMID- 1994124
TI  - Changes in anxiety among abstinent male alcoholics.
AB  - Symptoms of anxiety are prevalent features of alcoholics seeking treatment. In
      the present study levels of state anxiety among male primary alcoholics (with no
      preexisting major psychiatric disorders) were examined 3 times per week during
      inpatient treatment for alcoholism and again at 3 months following treatment. The
      171 male alcoholics also completed the trait scale of the State Trait Anxiety
      Inventory upon admission to an inpatient program and at 3 months following
      treatment. Results indicate that recently detoxified males experience multiple
      anxiety symptoms, with 40% reporting significantly elevated levels of state
      anxiety at admission (greater than or equal to 75th percentile). By the second
      week of treatment state anxiety scores typically returned to the normal range
      although symptoms continued to decrease significantly with each week of continued
      abstinence. Elevated levels of anxiety symptoms were more common among primary
      alcoholics with a history of panic episodes or generalized anxiety disorder
      symptoms. While abstainers and relapsers did not differ in level of anxiety
      observed during treatment, the relapsers report significantly higher state and
      trait anxiety scores at follow-up.

PMID- 1994125
TI  - Antisocial alcoholics: are there clinically significant diagnostic subtypes?
AB  - Of 360 alcoholic male inpatients assessed with a diagnostic interview, 106 (29%)
      were found to have a co-occurring diagnosis of antisocial personality. Of these
      ASP alcoholics, 86 were further subdivided into those with only ASP and
      alcoholism (n = 38), those with ASP, alcoholism and drug dependence (n = 30) and
      those with ASP, alcoholism and depression (n = 18; 9 of whom also had drug
      abuse). Comparisons among the three antisocial groups indicated that they
      differed in measures of psychopathology and course and severity of alcoholism.
      When the ASP groups were compared to an alcoholism only group, an earlier onset,
      more rapid course and increased percentage of many alcoholism symptoms were found
      in the ASP groups, confirming the findings of other studies.

PMID- 1994126
TI  - Development of a measure examining children's roles in alcoholic families.
AB  - A measure assessing the roles played by children in their alcoholic families is
      presented. In Study 1, an item pool was generated targeting four distinct roles
      discussed in the alcohol literature, and the items were reviewed by a panel of
      experts. The Children's Roles Inventory (CRI) was then administered to 140 adult
      children of alcoholics and their responses were used to refine the measure.
      Observed levels of internal consistency seemed adequate (Cronbach's alpha ranged
      from .89 to .95). In a replication effort (Study 2), the CRI was administered to
      142 adult children of alcoholics. Internal consistency remained at acceptable
      levels, ranging from .90 to .95. Study 3 examined the CRI's convergent and
      discriminant validity. A sample of 138 adult children of alcoholics as well as a
      sample of 105 adults from nonalcoholic families completed the CRI, a measure of
      self-esteem and an index of one's use of social support. Reliability results from
      Studies 1 and 2 were replicated (in both samples). Likewise, in both samples the
      CRI subscales were differentially predictive of self-esteem as well as size of
      and satisfaction with one's social support network.

PMID- 1994127
TI  - Children of alcoholic parents in the community.
AB  - The relationship between parental alcoholism and risk for maladjustment in the
      offspring was investigated in a community sample. Children of parents who met
      criteria for DIS/DSM-III alcohol abuse or dependence and children of parents who
      met criteria for ten other diagnoses were compared to children of "normal"
      parents. The data were obtained from the merging of the data banks of two major
      psychiatric epidemiology studies of the adult (17-64) and child (4-16) population
      of Puerto Rico. Results indicated that parental alcoholism in addition to
      creating an adverse family environment had an effect on the relative risk for
      maladjustment in the offspring (as measured by scores on the Child Behavior
      Checklist). Although previous studies have reported higher levels of
      externalizing behaviors in children of alcoholics, an increased risk for
      internalizing symptoms was observed in the children studied. Similar findings
      were obtained for the children of parents with other psychiatric disorders
      suggesting that the effects of parental alcoholism in children ages 4 to 16 may
      not be different from the consequences of parental mental illness per se.

PMID- 1994128
TI  - Abstracts, 20th annual meetings. Keystone Symposia on Molecular and Cellular
      Biology. Molecular approaches to the study of thyroid hormone action. March 8-15,
      1991.

PMID- 1994129
TI  - Abstracts, 20th annual meetings. Keystone Symposia on Molecular and Cellular
      Biology. Monoclonal antibodies. March 10-16, 1991.

PMID- 1994130
TI  - Abstracts, 20th annual meetings. Keystone Symposia on Molecular and Cellular
      Biology. Molecular biology and immunopathogenesis of rheumatoid arthritis. March
      15-21, 1991.

PMID- 1994131
TI  - Abstracts, 20th annual meetings. Keystone Symposia on Molecular and Cellular
      Biology. Manipulation of the avian genome. March 21-26, 1991.

PMID- 1994132
TI  - Abstracts, 20th annual meetings. Keystone Symposia on Molecular and Cellular
      Biology. Molecular biology of human pathogenic viruses. March 8-15, 1991.

PMID- 1994133
TI  - Education and the Mayos.

PMID- 1994134
TI  - Rediscovering tactile agnosia.
AB  - Eighty-four patients with damage to various levels of the nervous system, ranging
      from the peripheral nerves to the cerebral cortex, underwent somesthetic
      assessment in order to determine the degree to which basic and complex perceptual
      and motor disorders affect tactile object recognition (TOR) and to determine
      whether TOR can be impaired in the absence of more basic sensorimotor
      imperception. The results suggest that (1) basic and intermediate disorders of
      somesthetic function impair TOR but are commensurately more severe for any given
      degree of TOR impairment in patients with peripheral lesions than in patients
      with cortical lesions; (2) neither hemiparesis nor hemianopia alone precludes
      normal TOR; (3) hemineglect contributes substantially to TOR impairment; (4)
      impairment of TOR can occur in the absence of more basic somesthetic dysfunction
      and constitutes tactile agnosia; (5) tactile agnosia is a subtle, nondisabling
      disorder that should be distinguished from the nonagnosic, severe and disabling
      disorder, astereognosis; and (6) tactile agnosia results from unilateral damage
      to parietotemporal cortices, possibly including the second somatosensory cortex,
      in either hemisphere.

PMID- 1994135
TI  - Essential thrombocythemia in young adults.
AB  - Essential thrombocythemia is typically a disorder of adults in the sixth or
      seventh decade of life and is characterized by frequent thrombohemorrhagic
      complications. In young patients, the optimal management of complications is
      controversial. We studied 56 young adults (33 female and 23 male patients) with a
      diagnosis of essential thrombocythemia. The mean duration of follow-up was 4.68
      years. The mean platelet count at diagnosis was 1,328,000/mm3. Platelet
      aggregation studies in 21 patients demonstrated hypoaggregation to epinephrine;
      spontaneous platelet aggregation was present in 4. At diagnosis, 39 patients were
      asymptomatic, and thrombocytosis was discovered incidentally. Throughout follow
      up (up to 20 years), 24 patients remained asymptomatic. Thrombotic complications
      developed in 24 patients; they were life-threatening in only 3. The most common
      vaso-occlusive symptoms were migraine headache (in 12 patients) and
      erythromelalgia (in 3). Minor hemorrhagic complications occurred in six patients,
      and none was life-threatening. Serious complications (one cerebral and two
      myocardial infarctions) occurred in three patients, all of whom recovered. Two
      deaths occurred, neither of which was attributable to essential thrombocythemia.
      The treatment regimens used were chemotherapy in 9 patients, antiaggregating
      agents in 7, radioactive phosphorus in 1, the newer platelet-lowering agent
      anagrelide in 10, and only observation in 29. No treatment-related acute
      leukemias developed. This series of young patients with essential
      thrombocythemia, the largest to date, demonstrates a low incidence of life
      threatening complications and a favorable long-term prognosis. Therapeutic
      recommendations should remain conservative, and potential leukemogens should be
      avoided unless serious complications develop. Anagrelide may be useful in young
      patients with thrombocythemia who are symptomatic.

PMID- 1994136
TI  - Spontaneous renal rupture during pregnancy.
AB  - Spontaneous rupture of the renal parenchyma or renal pelvis during pregnancy has
      been previously reported in 16 cases. In the case we describe in this report, the
      patient initially had right flank pain and nausea for 48 hours, which progressed
      to severe abdominal symptoms that necessitated exploratory laparotomy.
      Cystoscopic placement of a ureteral stent relieved the obstruction and allowed
      spontaneous healing of the renal pelvis. Dilatation of the urinary collecting
      system commonly occurs during pregnancy. Spontaneous rupture of the renal
      parenchyma or renal pelvis, however, is unusual and often associated with
      diseased kidneys. Our case is the 8th one of spontaneous rupture of the renal
      collecting system with no identifiable underlying pathologic condition and the
      17th case of spontaneous renal rupture overall.

PMID- 1994137
TI  - Immunodermatology update: the immunologically mediated vesiculobullous diseases.
AB  - Before a specific diagnosis of an immunologically mediated blistering disease can
      be made, the clinical and histologic features and the results of direct and
      indirect immunofluorescence studies (with use of multiple substrates in some
      cases) must be assessed. For both subepidermal and intraepidermal groups of
      blistering diseases, direct immunofluorescence testing of perilesional tissue is
      critical for diagnosis. For these conditions, indirect immunofluorescence testing
      of serum is important for diagnosis and has a role in management of selected
      diseases. In dermatitis herpetiformis, indirect testing of serum for IgA
      antiendomysial antibodies is useful for both diagnosis and management. Indirect
      testing of serum for IgG antibodies to intercellular substance is important for
      diagnosis and, in conjunction with the clinical findings, can be used as a guide
      for monitoring disease activity in patients with pemphigus. Immunoelectron
      microscopy, immunoprecipitation, and immunoblotting studies have identified the
      sites of immune deposits and the specific antigens in most of the immunologically
      mediated bullous diseases. From a practical standpoint, however, direct and
      indirect immunofluorescence testing, in conjunction with clinical and histologic
      evaluations, is a simple, rapid, and relatively inexpensive tool for diagnosis
      and management.

PMID- 1994138
TI  - Reflections on the Canadian and American health-care systems.

PMID- 1994139
TI  - Peripheral tissue examination for malignant lesions of the skin.

PMID- 1994140
TI  - What has been rediscovered in "Rediscovering tactile agnosia"?

PMID- 1994141
TI  - The cancer patient with dyspnea: unusual cause?

PMID- 1994142
TI  - Myofascial pain syndromes.

PMID- 1994143
TI  - Sebastian Petrycy--famous Polish physician.

PMID- 1994144
TI  - Survival from out-of-hospital cardiac arrest. A multivariate analysis.
AB  - A recursive estimation model is used to investigate the roles of cardiopulmonary
      resuscitation (CPR) and advanced life support in improving survival from out-of
      hospital cardiac arrest. The importance of life support measures is clearly
      evidenced in the analysis: Fewer elapsed minutes between the cardiac arrest and
      the start of CPR increase the probabilities of both a favorable cardiac rhythm
      and defibrillation and the probability of survival. Similarly, a shorter elapsed
      time between the start of CPR and defibrillation is significantly related to a
      higher probability of survival of the cardiac arrest. Personal characteristics
      also contribute to survival, but primarily via their association with a favorable
      initial postarrest cardiac rhythm and the probability of defibrillation. The
      initial postarrest cardiac rhythm is shown to be an indicator of the heart's
      condition, but when other factors associated with survival are included in the
      analysis, it does not independently influence an individual's probability of
      survival.

PMID- 1994145
TI  - The validity of proxy-generated scores as measures of patient health status.
AB  - This study examines the validity of proxy assessments as substitutes for patient
      assessments of patient physical and psychosocial health status. Data were
      obtained from 275 patient-proxy pairs who were enrolled in a national study of
      Adult Day Health Care. Patients and proxies (informal caregivers such as spouses)
      were asked to complete the Sickness Impact Profile (SIP) based on the patients
      health status. Findings showed that patient-generated and proxy-generated
      physical scores were highly correlated, although proxies rated patients as
      slightly more impaired than the patient's rated themselves. The correlation
      between psychosocial scores was not high enough to consider proxy responses as
      valid substitutes for patient responses. We explored these differences in
      response by comparing regression equations predicting patient-generated and proxy
      generated physical and psychosocial SIP dimension scores. Variance in the patient
      generated psychosocial score was explained by physical function, psychological
      distress, cognitive status and patient age. Proxy-generated psychosocial scores
      were primarily explained by the caregiver's psychological distress and perceived
      burden. These findings point out the importance of considering the source of
      patient health status estimates when interpreting the results of research
      studies.

PMID- 1994146
TI  - Predicting nursing-home admission and length of stay. A duration analysis.
AB  - Information on who enters nursing homes and how much nursing-home care people use
      continues to be important for the consideration of various long-term care
      policies. Research on how characteristics of noninstitutionalized disabled
      elderly persons are related to both risk of admission and length of stay is
      presented here. Hazard models were developed using data from the 1982-84 National
      Long-Term Care Survey. Personal characteristics of elderly persons and state
      policy variables had varying effects on nursing-home use in a 2-year period.

PMID- 1994147
TI  - Selecting alternate drug therapies.
AB  - This study investigates the pharmacist's use of four cues--cost of alternative
      drug therapies to the patient, convenience afforded patients by alternative drug
      therapies, the patient's social support system, and the severity of the patient's
      illness--in a judgement of his or her likelihood of selecting an alternative drug
      therapy. A survey instrument using the four cues at low and high intensities
      resulted in a 2 x 2 x 2 x 2 crossover design with repeated measures. A linear
      prediction model for pharmacists' judgment concerning the likelihood of selecting
      an alternative drug therapy resulted. Sixty-four percent of the variation in
      these subjects judgment policies concerning the likelihood of selecting an
      alternative to the one prescribed was explained. Cost of therapy was weighed
      greatest among the variables studied, followed by severity, support, and
      convenience. However, cost of drug therapy was used least frequently by the
      subjects. Most often, pharmacists were concerned with the severity of a patient's
      illness, followed by support, convenience, and then cost. Pharmacists' use of
      patient convenience information is questioned.

PMID- 1994148
TI  - Performance of a five-item mental health screening test.
AB  - We compared the screening accuracy of a short, five-item version of the Mental
      Health Inventory (MHI-5) with that of the 18-item MHI, the 30-item version of the
      General Health Questionnaire (GHQ-30), and a 28-item Somatic Symptom Inventory
      (SSI-28). Subjects were newly enrolled members of a health maintenance
      organization (HMO), and the criterion diagnoses were those found through use of
      the Diagnostic Interview Schedule (DIS) in a stratified sample of respondents to
      an initial, mailed GHQ. To compare questionnaires, we used receiver operating
      characteristic analysis, comparing areas under curves through the method of
      Hanley and McNeil. The MHI-5 was as good as the MHI-18 and the GHQ-30, and better
      than the SSI-28, for detecting most significant DIS disorders, including major
      depression, affective disorders generally, and anxiety disorders. Areas under
      curve for the MHI-5 ranged from 0.739 (for anxiety disorders) to 0.892 (for major
      depression). Single items from the MHI also performed well. In this population,
      short screening questionnaires, and even single items, may detect the majority of
      people with DIS disorders while incurring acceptably low false-positive rates.
      Perhaps such extremely short questionnaires could more commonly reach use in
      actual practice than the longer versions have so far, permitting earlier
      assessment and more appropriate treatment of psychiatrically troubled patients in
      primary care settings.

PMID- 1994149
TI  - Measuring components of children's health status.

PMID- 1994150
TI  - HIV testing of asymptomatic patients in U.S. hospitals.
AB  - The human immunodeficiency virus (HIV) epidemic and the prevalence of HIV
      positive persons in the population has provoked marked anxiety among hospital
      staffs of acquiring nosocomially transmitted HIV infections. A national telephone
      survey of key staff in a sample of 561 acute-care hospitals was undertaken to
      describe the extent of asymptomatic HIV testing of patients, and variations
      between hospitals in testing practices. The interviews with the chiefs of
      medicine and surgery and the directors of nursing confirm the high level of
      anxiety among staff members about acquiring HIV from patients. In three of four
      hospitals, one or more of the three key clinical staff report asymptomatic
      testing of at least some patients. In 16.4% of the hospitals where asymptomatic
      testing is undertaken, one or more staff report that patients are either
      sometimes or never informed before testing and 38% are not counselled before
      testing. In 4.2% of the hospitals in which testing identified seropositive
      patients, infected persons are not always notified; one or more staff interviewed
      in 25.2% of the hospitals report that seronegative patients may not always be
      notified of results; likewise, 33.1% of the hospitals do not always include
      positive test results in hospital records, and 37.7% sometimes or always transfer
      seropositive patients to another hospital. A major finding is that there is a
      lack of congruence between the reports of the three different staff members
      interviewed in each hospital. These conclusions consider the likelihood of
      developing uniform practices between and within hospitals.

PMID- 1994151
TI  - The third Paul Ehrlich lecture. Basic research as forerunner of new medications.

PMID- 1994152
TI  - Fluoxetine, a selective inhibitor of serotonin uptake.
AB  - In summary, fluoxetine is a highly selective serotonin uptake inhibitor in vitro
      and in vivo. The conformation of fluoxetine, which resembles that of sertraline
      and other serotonin uptake inhibitors, appears to be a key feature that enables
      its high affinity and selective interaction with the serotonin transporter. The
      para-trifluoromethyl substituent, however, is also a pivotal structural element.
      The molecular pharmacology of fluoxetine has been well-defined, and its in vivo
      pharmacological effects appear to be mediated almost exclusively by serotonin
      uptake inhibition. Its selectivity for the serotonin transporter, lack of
      affinity for neurotransmitter receptors, and retention of selectivity following
      metabolism to norfluoxetine make fluoxetine a useful tool to explore
      pharmacologically induced increases in serotonin neurotransmission. Fluoxetine
      has found a variety of therapeutic application. Its use in treating depression
      has been most extensively studied, but controlled clinical studies also suggest
      the drug may have a role in treating obesity and bulimia. Moreover, a variety of
      other psychiatric disorders may be treatable with this drug. Regardless of the
      outcome of these clinical trials, it is apparent that fluoxetine has found a
      useful niche in therapy, and can be used as a probe to determine the role of
      serotonin in modulating human pathophysiologies.

PMID- 1994153
TI  - The concept of molecular structure in structure-activity relationship studies and
      drug design.
AB  - We can justify the use of any model, method, or algorithm if we clearly state our
      goals, understand the basis of our procedures, and fully appreciate the true
      nature and limitations of the results. As we have illustrated here, the creation
      of new wisdom may appear to be a consequence of our labors. There are cases,
      however, where this creation may be only an illusion. In any analysis of
      structure-activity, property-activity, or structure-property relationships, the
      degree of understanding of the nature of the starting data therefore determines
      the level of confidence ascribable to any result and prediction. This is, in
      essence, the message of our inquisitive meditations on the deep nature of
      structure-activity relationships.

PMID- 1994155
TI  - [Physicians have a moral obligation to be on call].

PMID- 1994154
TI  - Immunomodulating peptides of natural and synthetic origin.

PMID- 1994156
TI  - [Reevaluation of the problem of multiple significance].

PMID- 1994157
TI  - [Treatment of colorectal cancer with antineoplastic agents. Too early to
      introduce routine adjuvant therapy].

PMID- 1994158
TI  - [Nutritional support to patients with nutritional problems--to what price?].

PMID- 1994159
TI  - [Is the resistance against trimethoprim-sulfonamide increasing?].

PMID- 1994160
TI  - [Short stature. The debate concerns us].

PMID- 1994161
TI  - [Natural inhibitors or drugs can influence fat absorption].

PMID- 1994162
TI  - [A first rate symposium showed the front lines of the research on
      atherosclerosis].

PMID- 1994163
TI  - [Home oxygen therapy doubles survival rate in chronic hypoxia].

PMID- 1994164
TI  - [The number of invasive urologic interventions is decreasing. The effects of
      shockwave techniques are surveyed].

PMID- 1994165
TI  - [Post-transfusion purpura is an underdiagnosed condition].

PMID- 1994166
TI  - [Motivation for living wills can decrease the risk of meaningless medical
      measures].

PMID- 1994167
TI  - [How to notify a positive HIV test? Take time to listen and comfort].

PMID- 1994168
TI  - [The man behind the syndrome. Samuel A K Wilson and hepatolenticular
      degeneration. The discovery of the connection with liver cirrhosis become a
      landmark for pathology and neurology].

PMID- 1994169
TI  - [Early diagnosis is crucial for the prognosis of Wilson's disease].

PMID- 1994170
TI  - [Tooth grinding among wearers of amalgam fillings--a cause of high mercury
      release?].

PMID- 1994171
TI  - [A fall from a fruit tree--a case for an orthopedist in Mozambique].

PMID- 1994172
TI  - [Surface-immobilized heparin prevents platelet coagulation].

PMID- 1994173
TI  - [Guidelines for increased safety in anesthesiology].

PMID- 1994174
TI  - [The noise in health facility environments is a neglected problem].

PMID- 1994175
TI  - Persistently low natural killer cell activity and circulating levels of plasma
      beta endorphin: risk factors for infectious disease.
AB  - Beta endorphin levels were quantitated in plasma samples obtained from normal
      subjects (n = 81, 37% males and 63% females, age range 18-45 years) as a
      component of a prospective study examining the relationship of illness morbidity
      to natural killer cell activity and psychological indices of stress. The present
      study was designed to test whether beta endorphin levels contributed additionally
      to the explanation of illness outcome variance. In the larger study, persistently
      low NK (LNK) activity was associated prospectively with higher illness morbidity.
      The findings reported here suggest that the observed LNK activity might be
      affected by circulating levels of plasma beta endorphin, as lower endorphin
      levels predicted the LNK pattern, which in turn, predicted higher illness
      morbidity.

PMID- 1994176
TI  - Different responses between thyroxine 5'-monodeiodinase and protein disulfide
      isomerase activities to dietary fat and thyroid status in rat liver.
AB  - On the hypothesis that rat hepatic microsomal type I iodothyronine 5'
      monodeiodinase (MDI) would be identical to hepatic protein disulfide isomerase
      (PDI) (Boado et al. Biochem. Biophys. Res. Commun. 155 1297-1304 (1988)), we
      examined the responses of these enzyme activities to dietary fat and thyroid
      status in rats. The hepatic MDI activity was higher in rats fed high fat diet
      than in rats fed low fat diet, but the hepatic PDI activity showed the reverse
      responses to the diets. Propylthiouracil administration (hypothyroidism) lowered
      the MDI activity, but elevated the PDI activity. Thyroxine administration
      (hyperthyroidism) elevated the MDI activity but had no effect on the PDI
      activity. These results indicate that the two enzyme activities are regulated by
      different mechanisms in vivo, suggesting that MDI and PDI are not identical
      enzymes.

PMID- 1994177
TI  - Antimetastatic effects of liposome entrapped indomethacin.
AB  - The "in vivo"administration of sized liposomes encapsulating indomethacin to mice
      bearing 3LL tumor, significantly reduced the incidence and/or number of
      superficial lung metastases. Also liposomes encapsulating indomethacin had
      significant inhibitory effects on the experimentally induced lung metastases. We
      conclude: i) indomethacin encapsulated in liposomes is more efficient than the
      free drug in mediating the antimetastatic effects and ii) liposomes are an
      valuable vehicle in evading the side metastatic effects of this drug during
      indomethacin treatment of tumor bearing mice.

PMID- 1994178
TI  - Vasoinhibitory effect of NP-252, a new dihydropyridine derivative, in canine
      cerebral artery.
AB  - The vasoinhibitory effect of NP-252, a 1,4-dihydropyridine derivative Ca++
      antagonist, was examined in canine cerebral artery, and this effect was compared
      with that of nifedipine. NP-252 (10(-7)M) and nifedipine (10(-6) M) nearly
      abolished the contraction induced by addition of Ca++ to Ca(++)-free medium
      containing KC1. NP-252 (10(-6)M) and nifedipine (10(-6)M) attenuated the
      contraction produced by thromboxane A2 agonist (STA2) in normal medium, and the
      resultant contractions were 22% (n = 6) and 35% (n = 6) of the control
      contraction, respectively. The vasoinhibitory effects of NP-252 were
      significantly stronger than those of nifedipine in canine cerebral artery. NP-252
      (10(-7) and 10(-6) M) dose-dependently attenuated nifedipine-resistant Ca(++)
      contraction in the presence of STA2 in both canine cerebral and coronary
      arteries. The inhibitory effect of combined treatment with NP-252 (10(-6) M) and
      nitroglycerin (10(-6) M) on nifedipine-resistant Ca(++)-contraction in the
      cerebral artery was additive. These results indicate that NP-252 possesses a
      stronger vasoinhibitory effect than that of nifedipine in canine cerebral artery.

PMID- 1994179
TI  - Comparative studies of the effects of stilbene compounds on hepatic ornithine
      decarboxylase and S-adenosylmethionine decarboxylase induction in rats.
AB  - Trans-Stilbene oxide (TSO, 2 mmol/kg, ip.) induced ornithine decarboxylase (ODC)
      and S-adenosylmethionine decarboxylase (SAMDC) to 60-fold and 5-fold of the
      controls, respectively, in the liver of rats. Parallel to ODC induction, there
      was a marked increase in putrescine content to 50-fold of the control levels. Cis
      Stilbene oxide (CSO), a stereoisomer of TSO, also produced the induction of ODC
      and SAMDC and the increase in putrescine content. There was no difference in the
      ability to induce ODC and SAMDC between TSO and CSO with respect to the extents
      of induction and the time needed to reach maximal levels. Trans-Stilbene (TS), a
      mother compound of TSO, did not show such an effect on ODC, while cis-stilbene
      (CS) induced both ODC and SAMDC. Treatment with glutathione inhibited TSO- and
      CSO-mediated induction of ODC and SAMDC. These findings add new information
      concerning the abilities of TSO, CSO and CS on hepatic polyamine metabolism.

PMID- 1994180
TI  - Captopril attenuates reflex adrenergic response in essential hypertension.
AB  - An attenuation of adrenergic activity during the inhibition of endogenous
      angiotensin II formation was evaluated by determining plasma norepinephrine
      concentration after a single oral administration of captopril compared to that
      after nifedipine in essential hypertension. Captopril produced a fall in mean
      arterial pressure (-24 +/- 2 mmHg, p less than 0.01) which magnitude was the same
      as that gained by nifedipine (-22 +/- 3 mmHg, p less than 0.01). Reflex
      tachycardia due to hypotension was produced (+13 +/- 1 beats/min, p less than
      0.01) after nifedipine but not after captopril (-1 +/- 2 beats/min, p greater
      than 0.05). Although the enhancement of plasma renin activity induced by
      captopril (+1.54 +/- 0.56 ng/ml/hr, p less than 0.05) was similar (p greater than
      0.05) to that by nifedipine (+1.44 +/- 0.47 ng/ml/hr, p less than 0.05), plasma
      norepinephrine concentration increased less (p less than 0.01) after captopril
      (+100 +/- 23 ng/ml, p less than 0.05) than after nifedipine (+283 +/- 51 ng/ml, p
      less than 0.05). Thus, the diminished adrenergic activity is a likely candidate
      for the abolished reflex tachycardia after the inhibition of angiotensin I
      converting enzyme activity by captopril in essential hypertension.

PMID- 1994181
TI  - Assessment of sympathoneural activity in clinical research.
AB  - The assessment of autonomic nervous activity is a frequent and challenging goal
      of clinical research. The diverse current approaches are reviewed. Direct
      recording from the sympathetic input to muscle has the advantage of excellent
      time resolution and directness, but gives no information on the sympathetic input
      to the internal organs. Plasma noradrenaline concentration has limitations of
      specificity, some of which are overcome by single isotope radiotracer kinetic
      techniques. Other chemical markers are less satisfactory. End organ responses are
      generally limited to cardiovascular and cutaneous autonomic assessment, but
      sophisticated information is obtainable using power spectral analysis of heart
      rate variability. Assessment of receptor systems, of first and second messengers
      and radionuclide imaging of adrenergic nerves all give complimentary information.
      It is likely that a combination of these diverse techniques will advance
      understanding of the role of the autonomic nervous system in many disease states.

PMID- 1994182
TI  - Differential regional haemodynamic effects of the non-peptide angiotensin II
      antagonist, DuP 753, in water-replete and water-deprived Brattleboro rats.
AB  - Regional haemodynamic effects of DuP 753 were assessed in conscious unrestrained
      Brattleboro (i.e. vasopressin-deficient) rats, chronically instrumented with
      miniaturised pulsed Doppler flow probes and intravascular catheters. Responses to
      DuP 753 were assessed in water-replete animals and in animals following 14h water
      deprivation to render cardiovascular status dependent on the renin angiotensin
      system (RAS). In water-replete animals DuP 753 had little effect on mean arterial
      blood pressure, but there were dose-dependent tachycardias and increases in renal
      blood flow, associated with vasodilatations. There were also increases in
      mesenteric blood flow and vascular conductance, but these were not clearly dose
      related; DuP 753 had no significant effects on hindquarters haemodynamics. In
      water-deprived animals DuP 753 caused dose-dependent hypotension, tachycardia,
      and renal and mesenteric vasodilatations; hindquarters vasodilatation was not
      dose-dependent. In both conditions, in the presence of DuP 753 (10 mg/kg),
      captopril had little additional effect. DuP 753 appears to be an extremely
      effective tool for assessing the role of the RAS in cardiovascular regulation.

PMID- 1994183
TI  - Inhibition of the morphine withdrawal syndrome by a novel muscarinic antagonist
      (4-DAMP).
AB  - It has been recognized for many years that central cholinergic neurons are
      susceptible to inhibition by opiates and that during withdrawal their firing
      rates are enhanced. Nevertheless, classical nonselective muscarinic receptor
      antagonists have not been demonstrated to provide consistent inhibition of
      withdrawal symptoms in humans or in animal models. The purpose of this study was
      to determine whether selective blockade of central M1 or M2 muscarinic receptor
      subtypes could provide inhibition of naloxone precipitated withdrawal symptoms in
      morphine dependent rats. As with earlier human studies, both cardiovascular and
      behavioral measures of withdrawal were quantitated. The selective M2 receptor
      antagonist 4-DAMP was significantly more effective than the M1 antagonist
      pirenzepine in reducing both cardiovascular and behavioral symptoms. These
      results are consistent with a role for cholinergic neurons in the expression of
      certain morphine withdrawal symptoms and suggest that future therapies might be
      targeted towards central M2 receptors.

PMID- 1994184
TI  - Kynurenine and glycine enhance neuronal sensitivity to N-methyl-D-aspartate.
AB  - Neurones in rat hippocampal slices were excited by microiontophoretic
      applications of N-methyl-D-aspartate (NMDA) and kainate. Responses to NMDA were
      potentiated by glycine 300 microM or 1 mM in the perfusing medium. A small
      potentiation of kainate was not observed in the presence of the NMDA antagonist 2
      amino-5-phosphonopentanoic acid (2AP5). The potentiation of NMDA responses by
      glycine was not prevented by strychnine 5 or 30 microM and was also shown by D
      serine and L-kynurenine but not L-leucine. If sensitivity to NMDA was reduced by
      kynurenic acid, glycine and L-kynurenine produced a greater enhancement of NMDA.
      The requirement of NMDA receptor activation for the occupation of strychnine
      resistant glycine sites can thus be demonstrated in complex systems such as brain
      slices. It is possible that L-kynurenine may also be an endogenous ligand capable
      of modulating NMDA sensitivity.

PMID- 1994185
TI  - Effect of cocaine on responses of mouse phrenic nerve-diaphragm preparation.
AB  - Effects of 5 to 40 microM cocaine on the compound action potential (AP) and
      tension responses of the mouse phrenic nerve-diaphragm preparation were monitored
      following nerve and muscle stimulation at 37 degrees C. Cocaine caused
      concentration dependent reduction in amplitude of the nerve AP, muscle AP, and
      tension response to a single nerve stimulus, and greater reduction in amplitude
      of these responses to repetitive nerve stimuli at 100 Hz for 0.5 sec. Cocaine
      caused similar reduction in the muscle AP and tension responses to direct muscle
      stimulation in the presence or absence of curare, and markedly reduced the
      overshoot, total potential, and maximum rate of rise and fall of intracellularly
      recorded muscle AP, without affecting the resting potential, or the contracture
      responses evoked by caffeine. These results indicate that cocaine reduces
      skeletal muscle function by reducing the excitability of muscle and nerve
      membranes, without significantly affecting neuromuscular transmission, excitation
      contraction coupling or contractility.

PMID- 1994186
TI  - The design of a novel class of potassium channel activating drugs, 2-(2,2
      dimethylbenzopyran-4-yl)-pyridine-1-oxides.
AB  - The features of cromakalim responsible for its potassium channel activating
      property were investigated. A hypothesis relating three-dimensional structure to
      binding to a putative receptor was developed and used successfully to design the
      potent and structurally novel agents, 2-(2,2-dimethylbenzopyran-4-yl)-pyridine-1
      oxides.

PMID- 1994187
TI  - Interactions of cultured endothelial cells with TGF-beta, bFGF, PDGF and IGF-I.
AB  - Endothelial cells in culture synthesize the growth factors transforming growth
      factor beta (TGF-beta), basic fibroblast growth factor (bFGF), platelet derived
      growth factor (PDGF) and, perhaps, insulin like growth factor I (IGF-I). We have
      previously demonstrated that IGF-I and PDGF have both high affinity receptors and
      stimulate glucose and AIB uptake in the microvessel cells under study and that
      IGF-I, but not PDGF, has similar high affinity receptors in cultured large vessel
      endothelial cells. In the present study, cultured bovine endothelial cells were
      exposed to these four growth factors to determine a) their effects on the acute
      metabolic processes of neutral amino acid (AIB) and glucose uptake and b) their
      interactions at the endothelial cell surface. In microvessel endothelial cells,
      each growth factor stimulated AIB and glucose uptake 2-4 fold whereas in large
      vessel endothelial cells only bFGF stimulated glucose uptake. Each growth factor
      had specific high affinity binding to the microvessel cells that was not
      influenced by the presence of the other growth factors. In large vessel
      endothelial cells, similar high affinity binding was present only for IGF-I and
      to a lesser degree TGF-beta. When cells were exposed to a given growth factor for
      18 hours, homologous receptor downregulation was observed, with a maximal 60-95%
      decrease in surface binding. These findings suggest several potential levels of
      interaction of the growth factors TGF-beta, bFGF, PDGF and IGF-I in cultured
      vascular endothelial cells.

PMID- 1994188
TI  - Significant correlation between cerebrospinal fluid and brain levels of
      norepinephrine, serotonin and acetylcholine in anesthetized rats.
AB  - The present study was undertaken to determine cerebrospinal fluid (CSF) and brain
      levels of norepinephrine (NE), serotonin (5-HT) and their metabolites--3,4
      dihydroxyphenylacetic acid (DOPAC), 4-hydroxy-3-methoxyphenylacetic acid (HVA)
      and 5-hydroxyindole-3-acetic acid (5-HIAA)--in rats pretreated with 6
      hydroxydopamine (6-OHDA) or 5,7-dihydroxytryptamine (5,7-DHT). In the 6-OHDA
      pretreated rats, both CSF and brain concentrations of NE, DOPAC and HVA sustained
      significant decreases as compared with those in non-treated rats. Positive and
      significant correlations between CSF and brain levels were observed in respect to
      NE, DOPAC and HVA. In 5,7-DHT pretreated rats, both CSF and brain concentrations
      of 5-HT and 5-HIAA were significantly decreased. A positive and significant
      correlation between CSF and brain levels in respect to 5-HT and 5-HIAA was
      observed. Further studies were carried out to determine ACh levels of both the
      CSF and the brain in microspheres (MS)-treated rats, which are used as a model of
      microembolization. The CSF ACh concentrations in MS-treated groups were
      significantly decreased as compared with those in non-treated rats. The brain ACh
      contents also tended to decrease in this group. A positive and significant
      correlation was observed between CSF and brain levels of ACh. These findings
      suggest that NE, 5-HT and ACh concentrations in the CSF are direct indications of
      central noradrenergic, serotonergic and cholinergic nerve activity, respectively.

PMID- 1994189
TI  - Adaptive processes of the central and autonomic cholinergic neurotransmitter
      system: age-related differences.
AB  - Potential age-related differences in the response of the ileum strip longitudinal
      and circular muscle to repeated treatment with diisopropyl fluorophosphate (DFP)
      were evaluated in Sprague-Dawley rats. The response was measured in terms of both
      biochemical parameters (acetylcholinesterase-AChE inhibition, muscarinic
      acetylcholine receptor binding sites-mAChRs, choline acetyltransferase-ChAT) and
      functional responsiveness (contractility of the isolated ileum stimulated by
      cholinergic agonists). The biochemical data were compared with those obtained for
      the cerebral cortex. Male 3- and 24-month old rats were s.c. injected with DFP on
      alternate days for 2 weeks (doses in mg/kg: first 1.1, two of 0.7 and four of
      0.35). They were killed 48 hr and 7, 14, 21, 28 and 35 days after the last
      treatment. In the ileum strip of control rats there was a significant age-related
      decline of AChE, maximal density of 3H-QNB binding sites (Bmax) and ChAT. During
      the first week of DFP treatment the cholinergic syndrome was more pronounced in
      aged than in young rats, resulting in 35% and 10% mortality, respectively;
      subsequently the syndrome attenuated. At the end of DFP treatment ileal AChE were
      inhibited by about 30%; the down-regulation of mAChRs was about 50% in young and
      35% in aged rats. No significant differences in the recovery rate of AChE were
      noted between young and aged rats (normalization within 7 days). On the contrary,
      mAChRs normalized within 5 weeks in young and 3 weeks in aged rats. This was
      probably due to more adaptive decline in the former group. There was a post
      treatment increase of ChAT, transitory in young and persistent in aged rats. In
      spite of age-related marked loss of ileal mAChRs there were only little, although
      significant, changes in the contractile responsiveness of the isolated ileum to
      cholinergic agonists. Considerable DFP-induced down-regulation of mAChRs was not
      accompanied by changes in contractility stimulated by the agonists. The overall
      data indicate that age- and treatment-induced changes of AChE, mAChRs and ChAT in
      the ileum strip differ considerably from those observed in the cerebral cortex of
      the same rats.

PMID- 1994190
TI  - Methyl-substitution of benzene and toluene in preparations of human bone marrow.
AB  - The metabolism of benzene and toluene was investigated in preparations of human
      bone marrow incubated with S-adenosyl-L-methionine. Benzene undergoes a methyl
      substitution reaction to yield toluene as a metabolite. Furthermore, toluene
      undergoes methyl-substitution in preparations of human bone marrow incubated with
      S-adenosyl-L-methionine to yield o-xylene, m-xylene, and p-xylene. Metabolites
      were detected by gas chromatography and mass spectroscopy. No metabolism of
      either benzene or toluene was detected when a boiled bone marrow preparation was
      used in the incubation, demonstrating the enzymatic nature of the S-adenosyl-L
      methionine dependent methylation of both benzene and toluene.

PMID- 1994191
TI  - Who dies of what (these days)?

PMID- 1994192
TI  - MRI assessment programme: a clearer picture?

PMID- 1994193
TI  - Bridging the gender gap in contraception: another hurdle cleared.

PMID- 1994194
TI  - Drug availability.

PMID- 1994195
TI  - Recent trends in aboriginal mortality.
AB  - Mortality is an important measure of the extent of the health disadvantages
      experienced by Australia's Aborigines. In the absence of routinely available data
      on Aboriginal deaths, this paper has collated information from a number of
      sources. In addition to published reports and theses, it also includes
      unpublished data provided to the Australian Institute of Health by State and
      Territory health authorities. The review also draws on data on maternal deaths,
      collated on a triennial basis and published by the National Health and Medical
      Research Council. Despite improvements in some indices of mortality, the death
      rates of Aborigines, particularly for young and middle-aged adults, are
      unacceptably higher than those of non-Aboriginal Australians. Without substantial
      reductions in death rates, the expectation of life of Aborigines will remain
      comparable with that of people living in developing countries.

PMID- 1994196
TI  - Ear disease in three aboriginal communities in Western Australia.
AB  - Surveys of ear disease amongst Aboriginal people in two isolated bush communities
      (Wiluna and La Grange) and one urban community (Kwinana) in Western Australia
      were undertaken in 1988 or 1989. The age-adjusted prevalence odds ratio (relative
      risk) of perforations of the tympanic membrane for Wiluna compared with Kwinana
      was 5.0 (95% confidence interval [CI] 2.7-12.2) and 6.8 (95% CI 3.5-13.9) for La
      Grange compared with Kwinana. The relative risk of mild hearing loss, in
      comparison with Kwinana, was 2.5 (95% CI 1.5-4.3) for Wiluna and 3.2 (95% CI 2.0
      5.0) for La Grange. There was no significant difference in the relative risk of
      moderate or severe hearing loss or impedance pattern B, usually interpreted as
      "glue ear", in any of the three communities. Overall, the urban Aboriginal
      community had less ear disease and hearing loss than either of the isolated bush
      communities, but even this community did not approach the much lower levels of
      prevalence in Australia as a whole.

PMID- 1994197
TI  - Pregnancy outcomes in primigravid women aged 35 years and over in South
      Australia, 1986-1988.
AB  - The South Australian perinatal data collection for 1986-1988 was used to compare
      the characteristics and outcomes of singleton pregnancies in 515 primigravid
      women aged 35 years and over with those in 4175 younger primigravid women aged 20
      29 years. Notable differences observed were a higher prevalence of medical,
      obstetric and labour complications and assisted deliveries in the older group.
      Breech presentations were almost twice as common in the older women, as were
      caesarean sections. Only 27% achieved a spontaneous vaginal delivery. The mean
      duration of hospital stay for the older women was longer for both vaginal and
      caesarean deliveries. However, although their babies were more likely to be
      premature or of low birthweight, the perinatal mortality rate was not
      significantly increased and the great majority of older primigravid women managed
      by modern obstetric methods can expect a good pregnancy outcome.

PMID- 1994198
TI  - Seroepidemiology of hepatitis B infection in children in Vanuatu. Implications
      for vaccination strategy.
AB  - Four hundred and eighty-two unvaccinated children from three different age groups
      (12-18 months, 30-42 months, 54-115 months) in a hepatitis B virus (HBV) endemic
      area were tested for markers of HBV infection. HBV seromarkers were detected in
      52.3% of children and 26.9% were hepatitis B surface antigen (HBsAg) positive.
      Evidence of infection was related to age, with HBV seromarker rates highest
      (67.5%) in school children aged 56-115 months. The HBsAg positive rate was
      highest (30.1%) in children 30-42 months of age. However, even children in the
      youngest age group (12-18 months) had high seromarker (26.8%) and HBsAg positive
      (17.0%) rates. A high proportion of HBsAg positive children (83.8%) were also
      hepatitis Be antigen (HBeAg) positive. Mothers of children in the youngest age
      group (12-18 months) were also tested, and 24.5% were HBsAg positive. Factors
      associated with higher rates of infection in children included maternal HBeAg
      positivity (for children in the youngest age group), increasing age, and
      residence on the islands of Emao or Nguna. Higher rates of HBsAg positivity were
      associated with these factors and with being male. Crossinfection between
      children is probably the most important source of infection, based on the
      evidence of the high rate of HBeAg positivity in children and the rising
      infection rate with age. A possible vehicle of spread is through skin infections
      and skin sores which are highly prevalent in children in Vanuatu. Since this
      study indicates that both perinatal and early child-to-child transmission are
      occurring, the most practical strategy to prevent the majority of infections is
      to vaccinate all children, commencing at birth and completing the course early in
      the first year of life.

PMID- 1994200
TI  - Child sexual abuse--the problem for medical practitioners in small towns.

PMID- 1994199
TI  - Hepatitis B infection of children in a mixed-race community in western New South
      Wales.
AB  - A seroprevalence survey of markers of hepatitis B virus (HBV) infection in
      children aged 0-16 years was conducted in a mixed-race township in western New
      South Wales. A total of 408 children were screened representing 95% of the total
      0-16-year-old population. Of the Aboriginal subjects, 69% had seromarkers which
      indicated previous infection with HBV and 14% were hepatitis B surface antigen
      (HBsAg) seropositive. In the non-Aboriginal subjects the prevalence of
      seromarkers was 10% with no subjects HBsAg positive. The township provided an
      ideal setting for studying possible crossinfection from children in a high risk
      (Aboriginal) population group to children in a low-risk (non-Aboriginal) group.
      The ratio of children in the high-risk group for HBV infection to those in the
      low-risk group was approximately 2.7:1. Although HBsAg was highly endemic in the
      Aboriginal population, the data indicate that little crossinfection has occurred.
      We conclude that in this and similar mixed-race communities action should be
      taken to accelerate vaccination programmes aimed at reducing HBV infection among
      neonates and children in the high-risk groups. This will provide an immediate
      overall reduction of potential risk to both high-risk and low-risk groups while
      the issue of universal vaccination is considered further.

PMID- 1994201
TI  - Work in a shanty town in South Africa.

PMID- 1994202
TI  - Sunburn and other superficial burns. The ABCDs of management in the first four
      hours: a personal view.

PMID- 1994203
TI  - An epidemiological study of snake bite envenomation in Papua New Guinea.
AB  - We report a study of 347 patients with snake bite envenomation in Papua New
      Guinea. The male: female ratio of the victims was 1.6:1 and their mean age was
      24.5 years; 26% were children less than 15 years old. In all cases in which the
      bite site was known (334) the snake had bitten the extremities of the victim,
      with 71.3% of these bites being on the ankle or below. The patients came from
      three regions: urban Papua, rural Papua and (mostly rural) New Guinea. Snake
      bites occurred more frequently during the daytime in all regions, but this
      pattern was less obvious in New Guinea (P = 0.004), reflecting the predominance
      of the death adder (Acanthophis antarcticus) in New Guinea and of the taipan
      (Oxyuranus scutellatus canni) in Papua. Bites were commoner in the rainy season
      (November to April) in all groups, but this was less noticeable in rural Papua
      and New Guinea (P = 0.004). This may relate to seasonal activities of the rural
      population. The female:male ratio for patients from rural areas was higher for
      those 30 years of age and over than for those under 30 (P = 0.034), probably
      reflecting the increased gardening workload of older women. The incidence of
      envenomation and mortality rates after snake bite in Papua appear to have changed
      little over 25 years. However, increased relative numbers of taipans seem to be
      occurring in central Papua possibly related to the cane toad (Bufo marinus) and
      deforestation. We calculate the annual incidence of envenomation and the
      mortality rate per 100,000 to be 81.8 and 4.3, respectively, for rural central
      Papua, 21.8 and 2.1 for urban central Papua, and 3.0 and less than 1.0 for the
      Madang region of New Guinea. The importance of a standard management protocol and
      of improved first aid are emphasised.

PMID- 1994204
TI  - Spontaneous perforation of the cervical oesophagus.
AB  - A case of spontaneous perforation of the cervical oesophagus is presented. It
      appears to be the tenth such case in the world medical literature, and the first
      to be reported from the Southern Hemisphere. The need for awareness of this
      pathologic entity is stressed, and cold water polydipsia is suggested as a
      diagnostic marker.

PMID- 1994205
TI  - Improved left ventricular function after renal transplantation.
AB  - Patients with severely impaired left ventricular function are known to have a
      poor prognosis. We describe a 20-year-old man with end-stage renal failure, on
      dialysis, with severely impaired left ventricular function which dramatically
      improved after renal transplantation. This suggests that poor left ventricular
      function need not preclude renal transplantation and may, in fact, offer an
      alternative to combined renal and cardiac transplantation.

PMID- 1994207
TI  - An unusual intrabronchial foreign body in an asthmatic patient.

PMID- 1994206
TI  - Towards the development of the ideal malaria vaccine. A decade of progress in a
      difficult field.
AB  - Malaria remains one of the world's most serious diseases, affecting the lives of
      up to 500 million people. The rapid development of drug resistance enhances the
      need for the development of a vaccine. Since the first cloning of malaria
      proteins early in the last decade, there have been a number of "subunit" vaccine
      trials involving humans and monkeys. During this time, our understanding of the
      basic immunobiology of malaria has increased; different immune mechanisms are
      required to combat the different stages in the life cycle of the parasite, and
      the future vaccine will have to stimulate these different effector mechanisms.
      There has been steady progress over the last decade toward an effective vaccine,
      but a great deal of further effort is still required.

PMID- 1994208
TI  - Envenomation by the common black window spider.

PMID- 1994209
TI  - Stress and hypertension: a case.

PMID- 1994210
TI  - Environmental manganese toxicity.

PMID- 1994212
TI  - Chronic fatigue syndrome and invalid pensions.

PMID- 1994211
TI  - Public attitudes to smoke-free zones in restaurants: an update.

PMID- 1994213
TI  - Euthanasia and the "do not resuscitate" order.

PMID- 1994214
TI  - Too much diligence?

PMID- 1994215
TI  - Who cares for the carer of the old and ill?

PMID- 1994216
TI  - Food costs and nutrition in remote areas.

PMID- 1994217
TI  - The injecting and sexual behaviour of intravenous drug users.

PMID- 1994218
TI  - Child health in the Third World.

PMID- 1994219
TI  - Eosinophilia-myalgia syndrome associated with L-tryptophan use.

PMID- 1994220
TI  - Thoracic outlet syndrome: a case for routine preoperative neurophysiological
      testing.

PMID- 1994221
TI  - Human insulin.

PMID- 1994222
TI  - Health problems in the Persian Gulf.

PMID- 1994223
TI  - The role of the professional journal.

PMID- 1994224
TI  - Nursing and the philosophy of science.
AB  - Throughout its history, nursing has struggled with definitional issues. Embedded
      firmly in tradition mothering roles according to McCloskey and Grace (1985),
      nursing has found it difficult to make transitions into the professional and
      scientific realms. The professional and scientific status of nursing may not be
      as gloomy as McCloskey and Grace put it. Leddy and Pepper (1989) for instance
      claim that nursing has, since the 1960s, dramatically evolved into a scientific
      discipline. The purpose of this paper is to: 1. redefine science in order to
      establish the basis of the debate on nursing as a science; 2. outline at least
      one philosophical position in science and examine how nursing might benefit from
      it; 3. assess or evaluate, in the light of the above points the possible
      usefulness of nursing science especially the use of paradigm concepts in nursing;
      4. finally question whether nursing wants to work towards paradigm status. In a
      small way this paper contributes to the debate on the nature of science as
      applied to nursing. It reflects on the progress being made through nursing
      models' paradigm concepts. The conclusion suggests that the concept of paradigm
      as used in nursing is in keeping with Kuhn's and therefore can be adopted as a
      potentially useful framework.

PMID- 1994225
TI  - Teaching and assessing on course for change.
AB  - This paper argues that the concept of change is a valuable tool for the
      development of continuing education which is relevant to the personal needs of
      nurse practitioners and to clinical practice. The context for this discussion is
      a teaching and assessing course which holds the concept of change as the central
      philosophy for curriculum structure. The paper begins by describing the course
      philosophy, curriculum models and outline structure which typify this course. The
      second part of the paper describes research used to evaluate the 13 courses which
      have been held and the main conclusions of this research. It is concluded that
      this course has proven educational benefits and effects on clinical practice
      which include the development of critical reflectivity, acceptance of change,
      increase in self confidence and an increase in self-directed learning.

PMID- 1994226
TI  - Nurses' interpersonal skills: a study of nurses' perceptions.
AB  - Six Category Intervention Analysis was used as the framework of a study which
      involved asking 117 trained nurses to rate their interpersonal skills along six
      dimensions. The findings suggested that the nurses viewed themselves as being
      more skilled in offering support, information and prescription in their dealings
      with patients and less skilled in being catalytic, cathartic and confronting in
      similar circumstances. The findings in this study were similar to those of
      previous studies in this field. The study has implications for the development of
      interpersonal skills training programmes for nurses.

PMID- 1994227
TI  - The caring attitude in nursing practice: a repertory grid study of trained
      nurses' perceptions.
AB  - The process of caring is central to nursing practice but it remains a poorly
      defined concept in nursing practice and education. A small number of studies of
      caring in the field of nursing have been undertaken, but these have tended to be
      more quantitative in nature. This paper describes a qualitative study designed to
      explore nurses' perceptions of the concept of caring. Kelly's (1955) personal
      construct theory and the repertory grid interview technique were used to elicit
      trained nurses' views about caring in relation to the practice of nursing. A
      strategic informant sample of 25 nurses was chosen. A total of 200 verbal
      descriptions (constructs) were generated from interviews, and these were analysed
      into similar content areas. Seven categories emerged from the analysis to provide
      a detailed description of caring. These include: a) personal qualities; b)
      clinical work style; c) interpersonal approach; d) level of motivation; e)
      concern for others; f) use of time; and g) attitudes. There were very few
      constructs related to physical aspects of care. The findings are offered as
      reflection of British nurses' perceptions of caring. Some possible applications
      of the results for nursing practice, education and research are considered.

PMID- 1994228
TI  - Nursing education and definition of the professional nurse role. Expectations and
      knowledge of the nurse role.
AB  - The aim of nursing education is a development of the nursing profession. One way
      to promote development is to clarify the professional role. The role definition
      for nursing is mostly transmitted through tacit knowledge. We consider that the
      professional development of the nursing profession in Sweden requires a clear and
      well-defined nurse role. Stated goals of professional programmes for nursing do
      not include the entire body of tacit knowledge. The overall development requires
      recognition of a professional status together with a clear and well-defined role.
      We have found a significant change in the distribution of role-conceptions which
      occurred after the nurses had experienced their first year as registered nurses,
      and which did not occur during the educational process. This indicates that the
      conceptions of the need for a more clearly defined nursing role are assimilated
      during work experience. This confirms the necessity and importance of role
      modelling, role repetition and interactions with a professional group as part of
      the educational process.

PMID- 1994229
TI  - A model of evaluation exemplified by Swedish nursing education.
AB  - In an historical perspective it can be seen that the target for educational
      evaluation in Swedish nursing education was changed from that of student to
      programme evaluation. Since education, however, is an interaction of student
      prerequisites and educational goal-directed influences, there is a need for a
      more general evaluation model. This should preferably incorporate both student
      and programme influences over time at different levels, from classroom to
      societal level. Such a model is presented here based on data from a Swedish
      longitudinal twin project (Fischbein, 1979). A discussion of the model is
      initiated from an example of a recent evaluation study made of nurse education in
      Sweden.

PMID- 1994230
TI  - The assessment of student nurses.
AB  - This paper starts from the personal view that there are a number of issues
      related to the process of assessment which require investigation. It is suggested
      that a model of the assessment process might help clarify the present situation.
      The Brunswik lens model is explained and then expanded and adapted to facilitate
      its application to the assessment of student nurses in the clinical environment.
      Finally an 'armchair' evaluation of the model is undertaken with suggestions
      being offered for future investigation strategies.

PMID- 1994231
TI  - Improving feedback on student papers: a quantitative method which aids marking
      and gives valid feedback.
AB  - A quantifying method of marking was developed to aid in consistent and thorough
      marking of student papers and to improve the manner and validity of feedback.
      This feedback is on common technical writing skills. Giving feedback on technical
      writing skills, as opposed to concentrating on critical thinking skills, is
      defended. The benefits and purposes of this marking method are further developed.
      Implementation of the method is outlined, and a completed Quantitative Feedback
      form is demonstrated. Through evaluation, the method has been found effective for
      aiding marking and for clearly identifying strengths and weaknesses in writing.

PMID- 1994232
TI  - The use of team teaching for communication skills training in nurse education.
AB  - Team teaching is a strategy which offers an alternative to traditional single
      teacher methods. However, little has been written about its use in nurse
      education. This paper examines team teaching and its rationale, discussing
      possible advantages and disadvantages. The use of this strategy as a means of
      teaching communication skills to Registered Mental Nurse (RMN) students is
      described and basic principles related to team teaching are offered as guidelines
      to enable others to implement this approach in a variety of subject areas.

PMID- 1994233
TI  - Piaget's theory of cognitive development may be useful in deciding what to teach
      and how to teach it.
AB  - The author outlines the relevant aspects of Piaget's theory of cognitive
      development and argues that, far from being restricted to childhood development,
      the theory has relevance for adult learners. An attempt is made to demonstrate
      the importance of practice within the educational framework of the student who is
      learning to become a nurse. It is argued that emphasis should be placed upon the
      provision of environments which allow the student to practise the schemas which
      he already possesses in order to provide opportunities for the elaboration of
      these schemas. Piaget's view that the existence of 'schema is motivation in
      itself' and the environment is important insofar as it should be geared to
      'match' the classroom experiences of the student with the student's ability to
      respond to them, is outlined; with the contention that the most important means
      of growth is through action and through operations that the student himself
      performs on the environment. The author concludes with a note of caution for
      curriculum planners in a Project 2000 scenario who may promote theory at the
      expense of practice.

PMID- 1994234
TI  - Librarian or educator: into the classroom.
AB  - There is a traditional view of librarians as keepers of information. This paper
      reports on the development of a post of Tutor Librarian who is actively involved
      in nurse education and inservice training. Project 2000 and its accompanying
      curriculum changes provide an opportunity to develop the Tutor Librarian's role.

PMID- 1994235
TI  - The question of money.

PMID- 1994236
TI  - AMA policy: you can shape it.

PMID- 1994237
TI  - Subtracting cigarettes without adding pounds.
AB  - Many smokers report that the greatest hindrance to quitting smoking is their fear
      of gaining weight. Everyone knows someone who threw away the cigarettes and
      picked up 30 pounds. Although smokers see their habit as socially unacceptable,
      they see obesity in a worse light. Good interventional skills and awareness of
      one's own habits can prevent kicking the habit from become a "weighty" problem.

PMID- 1994238
TI  - Fluoxetine (Prozac): a profile and clinical recommendations.

PMID- 1994239
TI  - HIV/AIDS in Missouri: an assessment of physician attitudes and practices.
AB  - Fewer than half of Missouri physicians responding to a statewide survey are
      willing to treat patients with HIV infection, and even fewer are willing to treat
      patients with AIDS. The authors discuss these survey results and their
      implications for patient care in Missouri.

PMID- 1994240
TI  - Tuberculin skin testing: interpretation and management. Answers to commonly asked
      questions.

PMID- 1994241
TI  - Primary amyloidosis of the lower urinary tract: a case report.
AB  - Primary amyloidosis of the lower urinary tract is a rare condition with an
      excellent prognosis in most cases. In this case, the author describes a case
      primarily involving the urinary bladder.

PMID- 1994242
TI  - The transformation of American physicians from professionals into providers.

PMID- 1994243
TI  - Evaluation of mutagenic effect of the antihypertensive drug methyldopa (Aldomet)
      on mammalian systems in vivo and in vitro and on Allium cepa.
AB  - The antihypertensive drug methyldopa (Aldomet) was tested for possible
      clastogenic activity on normal and hypertensive rats and on human lymphocyte
      cultures and for its influence on the cell cycle of Allium cepa. The drug had no
      clastogenic effect on rat bone marrow cells but showed a toxic effect on A. cepa
      root tip cells and significantly increased the frequency of sister-chromatid
      exchanges in lymphocyte cultures, without any effect on the frequency of
      chromosome aberrations.

PMID- 1994244
TI  - Establishment of dose-response relationships between doses of Cs-137 gamma-rays
      and frequencies of micronuclei in human peripheral blood lymphocytes.
AB  - It has been suggested that the yield of micronuclei in human peripheral blood
      lymphocytes could be used as a biological dosimeter in cases of radiation
      exposure. In the present study micronuclei were induced in lymphocytes by
      exposing human blood samples in vitro to various doses of Cs-137 gamma-rays. The
      blood samples were then cultivated using the cytokinesis block method. Coded
      programs were employed to establish the relationships between the frequencies of
      micronuclei and various doses of gamma-rays. The best fit was obtained by the
      linear-quadratic model, Y = c + aD + bd2, where Y is the yield of micronuclei, D
      is the dose in Gy and c, a, b, are constants. It seems there is a correlation
      between the yields of MN in mononuclear cells and the corresponding doses of
      radiation. Therefore an attempt was made to include these MN in the calculation
      of the dose-response relationship.

PMID- 1994245
TI  - Leather tanning workers: chromosomal aberrations in peripheral lymphocytes and
      micronuclei in exfoliated cells in urine.
AB  - A cytogenetic study was performed on workers of a leather tanning industry. Two
      different approaches for the biological monitoring of the individuals were used:
      chromosomal aberration analysis in peripheral lymphocytes and the frequency of
      micronucleated cells exfoliated in urine samples. 26 men working in the sections
      considered to present a greater risk were included in the study. Controls were 20
      men that were not exposed to chemicals. The percentage of abnormal cells was
      higher in workers than in controls. Smokers showed higher values of chromosome
      breaks than non-smokers in both groups. These differences were not statistically
      significant. The percentage of cells with chromatid and chromosome gaps in
      workers and controls was different (p less than 0.01). A slight but not
      significant increase in the mean percentage of micronuclei was observed in the
      exposed group. We conclude that exposure to chemicals during leather tanning did
      not produce genotoxic effects measured by chromosomal aberrations in peripheral
      lymphocytes and micronuclei in urine in this group of workers.

PMID- 1994246
TI  - Divergent effects of serotonin on coronary-artery dimensions and blood flow in
      patients with coronary atherosclerosis and control patients.
AB  - BACKGROUND: Studies in animals have shown that serotonin constricts coronary
      arteries if the endothelium is damaged, but in vitro studies have revealed a
      vasodilating effect on isolated coronary segments with an intact endothelium. To
      investigate the effect of serotonin in humans, we studied coronary-artery cross
      sectional area and blood flow before and after the infusion of serotonin in seven
      patients with angiographically normal coronary arteries and in seven with
      coronary artery disease. METHODS: We measured the cross-sectional area of the
      coronary artery by quantitative angiography and coronary blood flow with an
      intracoronary Doppler catheter. Measurements were obtained at base line and
      during intracoronary infusions of serotonin (0.1, 1, and 10 micrograms per
      kilogram of body weight per minute, for two minutes). We repeated the
      measurements after an infusion of ketanserin, an antagonist of serotonin
      receptors that is thought to block the effect of serotonin on receptors in the
      arterial wall but not in the endothelium. RESULTS: In patients with normal
      coronary arteries, the highest dose of serotonin increased cross-sectional area
      by 52 percent (P less than 0.001) and blood flow by 58 percent (P less than
      0.01). The effect was significantly potentiated by administration of ketanserin.
      In patients with coronary-artery atherosclerosis, serotonin reduced cross
      sectional area by 64 percent (P less than 0.001) and blood flow by 59 percent (P
      less than 0.001). Ketanserin prevented this effect. CONCLUSIONS: Serotonin has a
      vasodilating effect on normal human coronary arteries; when the endothelium is
      damaged, as in coronary artery disease, serotonin has a direct, unopposed
      vasoconstricting effect. When considered with other evidence, these data suggest
      that platelet-derived factors such as serotonin may have a role in certain acute
      coronary ischemic syndromes.

PMID- 1994247
TI  - Effect of intracoronary serotonin on coronary vessels in patients with stable
      angina and patients with variant angina.
AB  - BACKGROUND: Serotonin, a major product of platelet activation, has potent
      vasoactive effects in animal models, but its role in human coronary artery
      disease remains largely speculative. METHODS: Using quantitative coronary
      angiography, we compared the effects of the intracoronary infusion of graded
      concentrations of serotonin (10(-7) to 10(-4) mol per liter) on coronary vessels
      in two groups of patients with different clinical presentations of coronary
      disease (nine with stable angina and five with variant angina), with the effects
      in a control group of eight subjects with normal vessels on angiography. RESULTS:
      Normal coronary vessels had a biphasic response to intracoronary serotonin:
      dilation at concentrations up to 10(-5) mol per liter, but constriction at 10(-4)
      mol per liter. Vessels in patients with stable angina constricted at all
      concentrations, with mean (+/- SEM) maximal decreases in diameter of 23.9 +/-
      3.6, 33.1 +/- 3.9, and 41.7 +/- 3.1 percent from base line in proximal, middle,
      and distal segments at a serotonin concentration of 10(-4) mol per liter. Smooth
      segments constricted more than irregular segments (42.0 +/- 4.6 vs. 21.1 +/- 1.6
      percent). Four patients with stable angina had a marked reduction in collateral
      filling. All the patients with stable angina had angina during the intracoronary
      infusion of serotonin, and electrocardiographic changes were noted in six. All
      the patients with variant angina had angina, electrocardiographic changes, and
      localized occlusive epicardial coronary-artery spasm at concentrations of 10(-6)
      (n = 2) or 10(-5) (n = 3) mol per liter. CONCLUSIONS: Patients with stable
      coronary disease do not have the normal vasodilator response to intracoronary
      serotonin, but rather have progressive constriction, which is particularly
      intense in small distal and collateral vessels. Patients with variant angina have
      occlusive coronary-artery spasm at a dose that dilates normal vessels and causes
      only slight constriction in vessels from patients with stable angina. These
      findings suggest that serotonin, released after the intracoronary activation of
      platelets, may contribute to or cause myocardial ischemia in patients with
      coronary artery disease.

PMID- 1994248
TI  - Pulmonary aspergillosis in the acquired immunodeficiency syndrome.
AB  - BACKGROUND AND METHODS: Symptomatic pulmonary aspergillosis has rarely been
      reported in patients with the acquired immunodeficiency syndrome (AIDS). We
      describe the predisposing factors, the clinical and radiologic features, and the
      therapeutic outcomes in 13 patients with pulmonary aspergillosis, all of whom had
      human immunodeficiency virus (HIV) infection and 12 of whom had AIDS. RESULTS:
      Pulmonary aspergillosis was detected a median of 25 months after the diagnosis of
      AIDS, usually following corticosteroid use, neutropenia, pneumonia due to other
      pathogens, marijuana smoking, or the use of broad-spectrum antibiotics. Two major
      patterns of disease were observed: invasive aspergillosis (in 10 patients) and
      obstructing bronchial aspergillosis (in 3). Cough and fever, the most common
      symptoms, tended to be insidious in onset in patients with invasive disease
      (median duration, 1.3 months before diagnosis). Breathlessness, cough, and chest
      pain predominated in the three patients with obstructing bronchial aspergillosis,
      who coughed up fungal casts. Radiologic patterns included upper-lobe cavitary
      disease (sometimes mistaken for tuberculosis), nodules, pleural-based lesions,
      and diffuse infiltrates, usually of the lower lobe. Transbronchial biopsies were
      usually negative, but positive cultures were obtained from bronchoalveolar-lavage
      fluid or percutaneous aspirates. Dissemination to other organs occurred in at
      least two patients, and direct invasion of extrapulmonary sites was seen in two
      others. The results of treatment with amphotericin B, itraconazole, or both were
      variable. Ten of the patients died a median of 3 months after the diagnosis
      (range, 0 to 12 months). CONCLUSIONS: Pulmonary aspergillosis is a possible late
      complication of AIDS; if diagnosed early, it may be treated successfully.

PMID- 1994250
TI  - Graft-versus-host disease.

PMID- 1994249
TI  - Cesarean section before the onset of labor and subsequent motor function in
      infants with meningomyelocele diagnosed antenatally.
AB  - Background. Meningomyelocele can now be detected before birth. Few data are
      available on its natural history, however, and optimal management at the time of
      delivery is controversial, although it has been suggested that labor and vaginal
      delivery may cause pressure on exposed nerve roots, resulting in additional loss
      of neural function. Methods. To assess the effect of labor and the type of
      delivery on the level of motor function in fetuses with uncomplicated
      meningomyelocele, we identified 200 cases of this disorder, accounting for 95
      percent of the cases that occurred in the state of Washington during our 10-year
      study period. We compared the outcomes of 47 infants delivered by cesarean
      section before labor began, 35 delivered by cesarean section after a period of
      labor, and 78 who were delivered vaginally (another 40 were ineligible for the
      study). In cases of meningomyelocele detected prenatally, cesarean section was
      performed before the onset of labor if isolated meningomyelocele without severe
      hydrocephalus was present. The infants delivered in this manner were compared
      with those who were delivered either vaginally or by cesarean section after labor
      began. Results. At two years of age, the infants who had been exposed to labor
      were 2.2 times more likely to have severe paralysis than those delivered by
      cesarean section without labor (95 percent confidence interval, 1.7 to 2.8).
      Infants delivered by cesarean section before the beginning of labor had a mean
      (+/- SD) level of paralysis 3.3 +/- 3.0 segments below the anatomical level of
      the spinal lesion at two years of age, as compared with 1.1 +/- 2.3 for infants
      delivered vaginally and 0.9 +/- 4.1 for infants delivered by cesarean section
      after the beginning of labor (P less than 0.001 for both comparisons). Exposure
      to labor did not affect the frequency of neonatal complications or later
      intellectual performance. Conclusions. For the fetus with uncomplicated
      meningomyelocele, delivery by cesarean section before the onset of labor may
      result in better subsequent motor function than vaginal delivery or delivery by
      cesarean section after a period of labor.

PMID- 1994251
TI  - Spina bifida in infants of women treated with carbamazepine during pregnancy.

PMID- 1994252
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      excises. Case 10-1991. A 30-year-old man with polydipsia, hypopituitarism, and a
      mediastinal mass.

PMID- 1994253
TI  - Serotonin and acute ischemic heart disease.

PMID- 1994254
TI  - Diagnosis and management of neural-tube defects today.

PMID- 1994255
TI  - Death and dignity. A case of individualized decision making.

PMID- 1994256
TI  - Vitamin A and childhood mortality.

PMID- 1994257
TI  - Abnormalities of lipoprotein metabolism in the nephrotic syndrome.

PMID- 1994258
TI  - Recombinant erythropoietin to improve athletic performance.

PMID- 1994259
TI  - Analysis of aqueous humor in ocular toxoplasmosis.

PMID- 1994260
TI  - Sleep disorders and aging.

PMID- 1994261
TI  - Medical appropriateness of coronary angiograms.

PMID- 1994262
TI  - Maternal age and outcome of pregnancy (continued)

PMID- 1994263
TI  - The high cost of levamisole for humans.

PMID- 1994264
TI  - Traumatic intracranial aneurysms caused by missiles: their presentation and
      management.
AB  - Only 30 cases of traumatic intracranial aneurysm (TICA) secondary to missile
      injury have been reported to date. To these we add 15 more cases. Missile TICAs
      are often seen on a secondary branch of the middle cerebral artery and are
      usually accompanied by a intracerebral hematoma (80%) or by an acute subdural
      hematoma (26%). Fourteen of our cases were secondary to shrapnel injuries and
      only one was secondary to a bullet. None of the injuries was through-and-through.
      TICAs may enlarge in time and, seemingly inoffensive, may rupture and lead to
      death. All seven TICAs studied histologically proved to be false aneurysms. TICAs
      are best treated through trapping and excision. The outcome depends on the
      patient's status and level of consciousness before surgery. Indications for
      angiography are discussed.

PMID- 1994265
TI  - Orbitozygomatic temporopolar approach for a high basilar tip aneurysm associated
      with a short intracranial internal carotid artery: a new surgical approach.
AB  - For two cases of a high basilar tip aneurysm accompanied by a short intracranial
      internal carotid artery, the orbitozygomatic temporopolar approach consisting of
      an en bloc fronto-orbitozygomatic temporal craniotomy and temporopolar approach
      was carried out. On angiograms, the height of the bifurcation of an elongated
      basilar artery and the length of the intracranial internal carotid artery from
      the interclinoid line between the anterior and posterior clinoid process were 20
      mm and 6 mm in Case 1, and 18 mm and 5 mm in Case 2, respectively. The skin flap
      was separated subfascially to preserve the frontotemporal branch of the facial
      nerve. The fronto-orbitozygomatic temporal bone flap was made, and a part of the
      basal bony structures of the orbital roof, the sphenoid ridge, and the temporal
      bone were removed. The basilar tip aneurysm could be seen and clipped easily by
      upward and oblique viewing from below through the wide operative space consisting
      of the less retracted internal carotid and middle cerebral arteries, the
      oculomotor nerve, the tentorial hiatus, and the emptied anterior temporal fossa
      obtained by partial division of the temporal bridging veins. The operative
      procedure is presented in detail and compared with other surgical approaches that
      have been described previously.

PMID- 1994266
TI  - The history of the neurosurgical engine.
AB  - The opening of the skull of a living human being dates back to early
      civilization. The procedure may have been performed as early as the Neolithic
      period. Surgeons have continued to search for a better, easier, quicker, and
      safer method to open the skull. Today, most neurosurgeons are well acquainted
      with the surgical drill; however, few are familiar with the development of this
      instrument from its beginnings in dentistry to its use in modern neurosurgery. As
      cerebral localization advanced in the late 19th century, so, too, did the demands
      for better techniques for entering the cranial cavity and exposing more extensive
      areas of the brain. Mechanical devices began to appear in operating theaters
      throughout the world. Despite the enthusiasm of its inventors, the surgical
      engine was used by but a few pioneer cranial surgeons. The use of a surgical
      engine in the operating room has become commonplace. Its presence continues to
      demand respect. There is no doubt that this instrument has helped advance
      neurosurgery. Its development and refinement are rich in history and closely
      parallel the development of modern neurosurgery.

PMID- 1994267
TI  - Juvenile intervertebral disc calcification: recognition, management, and
      pathogenesis.
AB  - Juvenile intervertebral disc calcification is an uncommon disorder of childhood,
      characterized by calcification of the nucleus pulposus of one or more
      intervertebral discs. Calcification may remain dormant or subsequently become
      symptomatic. The symptoms include fever, malaise, and neck pain and are
      associated with an elevated erythrocyte sedimentation rate and, occasionally,
      leukocytosis. Although disc protrusion occurs in 38% of patients, neurological
      signs are distinctly uncommon. We report the case of a patient with a herniated
      T2-T3 calcified intervertebral disc and compressive myelopathy. Juvenile
      intervertebral disc calcification is generally a self-limiting disease that
      seldom requires an operation. The symptoms are transient, and resorption of the
      disc calcification is the rule once symptoms occur. Neither the cause of the disc
      calcification nor the trigger for the onset of symptoms is known. An inflammatory
      response within the disc appears to give rise to clinical symptoms and is
      associated with eventual resorption of the disc calcification.

PMID- 1994268
TI  - Direct endovascular thrombolytic therapy for dural sinus thrombosis.
AB  - Three patients, ages 51 to 71 years, sought treatment for symptomatic dural sinus
      thrombosis with occlusion and were treated by direct sinus perfusion with
      urokinase. All three patients had a dural arteriovenous fistula; one involved the
      inferior petrosal sinus and two involved the transverse sinus. Clinical findings
      included papilledema, diminished visual acuity, decreased mentation, and cranial
      nerve palsies. Diagnosis was made by cerebral arteriography and confirmed by
      sinus venography. All three patients were treated by a transjugular direct
      infusion of urokinase. In one patient, a transfemoral venous approach used
      initially was discontinued because of an infection. The period of continuous
      infusion for thrombolysis ranged between 4 and 10 days. In two patients, the
      clinical signs and symptoms improved with angiographic evidence of clot lysis and
      dural sinus recanalization. Angiography indicated that one patient had a partial
      resolution of a clot in the torcular herophili and transverse sinus but showed no
      clinical improvement. These preliminary results suggest that transjugular local
      infusion of thrombolytic agents can be an effective treatment for symptomatic,
      thrombosed dural sinuses. This selective lysis avoids thrombolytic effects that
      could aggravate or produce systemic hemorrhagic complications.

PMID- 1994269
TI  - Rupture of a giant carotid aneurysm after extracranial-to-intracranial bypass
      surgery.
AB  - We report a case of a fatal rupture of a previously unruptured giant aneurysm of
      the bifurcation of the internal carotid artery (ICA), which occurred after an
      extracranial-intracranial (EC-IC) bypass and the partial occlusion of the ICA.
      Interim angiography showed retrograde filling of the proximal middle cerebral
      artery to the aneurysm. There have been four previously reported cases of giant
      aneurysms rupturing after treatment with an EC-IC bypass and carotid ligation,
      and it appears likely that a change in pressure/flow dynamics produced by the
      bypass may have been the cause. The technique of carotid ligation with an EC-IC
      bypass is used frequently to treat unclippable intracranial aneurysms, and the
      resulting hemodynamic changes need to be considered carefully to prevent this
      type of complication. To minimize hemodynamic stress on the aneurysm, we suggest
      that 1) the bypass caliber should be as small as possible consistent with
      sufficient cerebral blood flow after ICA occlusion, and 2) complete ICA occlusion
      should be performed as soon as possible after the bypass.

PMID- 1994270
TI  - Abscess of the sphenoid sinus after transsphenoidal surgery.
AB  - A case of a bacterial abscess developing in the sphenoid sinus 2 weeks after
      transsphenoidal surgery is presented. Although abscesses within the sella turcica
      have been reported as rare complications of transsphenoidal surgery, this is the
      first reported case of the postoperative formation of an abscess of the sphenoid
      sinus. The patient sought treatment for severe headaches, nausea and vomiting,
      and marked temperature elevation. A computed tomographic scan demonstrated soft
      tissue and air within the sphenoid sinus. A regimen of stress doses of
      hydrocortisone and antibiotics was prescribed, and the patient underwent
      transsphenoidal drainage of the sphenoid sinus. The sella turcica was not
      involved. Anaerobic cultures were positive for Fusobacterium necrophorum.

PMID- 1994271
TI  - Progressive coma after the transsphenoidal decompression of a pituitary adenoma
      with marked suprasellar extension: report of two cases.
AB  - Two cases of neurological deterioration and coma after the transsphenoidal
      decompression of a pituitary adenoma with marked suprasellar extension and
      invasion of the 3rd ventricle are presented. Emergency ventricular shunting led
      to prompt neurological improvement, which, supplemented by radiation therapy,
      allowed long-term amelioration of symptoms. Three possible explanations for this
      complication are offered: 1) traction of the attached 3rd ventricle into the
      decompression site, causing increased obstructive hydrocephalus, 2) vasopressin
      release by surgical manipulation of the pituitary stalk and circumventricular
      organs causing cerebral edema, and 3) edema in the residual tumor secondary to
      surgical manipulation causing further hydrocephalus. Subsequent patients with
      similar clinical and imaging criteria will have a planned perioperative
      ventricular shunting procedure performed.

PMID- 1994272
TI  - Ectopic retinoblastoma within the 3rd ventricle: case report.
AB  - Ectopic intracranial retinoblastomas are rare. These tumors usually occur in the
      pineal, parasellar, or suprasellar regions several years after the successful
      treatment of ocular retinoblastomas with no evidence of direct extension or
      distant metastasis. We report here a case of ectopic retinoblastoma occurring
      within the third ventricle. The tumor was surgically excised by the
      transventricular approach. Ectopic retinoblastomas exhibit greater
      differentiation than one would expect to observe in a metastatic lesion of this
      tumor. The distinction of ectopic retinoblastomas and metastasis from ocular
      retinoblastomas is important, since ectopic retinoblastomas, unlike metastasis,
      can be successfully managed by intensive therapy including radical excision.

PMID- 1994274
TI  - Epidural tuberculoma of the spine: case report.
AB  - Epidural tuberculomas of the spine have been reported only rarely during the past
      few decades. A case of a surgically treated epidural tuberculoma of the thoracic
      spine in a 76-year-old women is presented.

PMID- 1994273
TI  - Long-term follow-up of patients with recurrent malignant gliomas treated with
      adjuvant adoptive immunotherapy.
AB  - Between August 1986 and October 1987, the Denver Brain Tumor Research Group
      conducted a clinical trial using autologous human recombinant interleukin-2 (rIL
      2)-activated lymphocytes to treat 20 patients with recurrent high-grade gliomas.
      The trial involved surgical resection and/or decompression followed by
      intracavitary implantation of lymphokine-activated killer (LAK) cells and
      autologous stimulated lymphocytes (ASL) along with rIL-2 in a plasma clot. One
      month later, stimulated lymphocytes and rIL-2 were infused through a Rickham
      reservoir attached to a catheter directed into the tumor bed. The LAK cells were
      rIL-2-activated peripheral blood lymphocytes cultured for 4 days; the ASL were
      lectin- and rIL-2-activated peripheral blood lymphocytes cultured for 10 days. Of
      the 20 patients treated, 11 were evaluated as a group (mean age, 44 years, range,
      15-61 years; mean Karnofsky rating, 69, range, 50-100; mean Decadron dose at
      entry, 14 mg/d, range, 0-32). The average number of lymphocytes implanted was 7.6
      x 10(9) (range, 1.9-27.5 x 10(9], together with 1 to 4 x 10(6) U of rIL-2. To
      date, 10 of the 11 patients died, all from recurrent tumor growth. The median
      overall survival time was 63 weeks (range, 36-201; mean, 86). The median survival
      time after immunotherapy was 18 weeks (range, 11-151; mean, 39). No significant
      difference in survival after immunotherapy was found between those patients who
      had received previous chemotherapy and those who had not. The use of steroids or
      prior chemotherapy did not influence the in vitro generation of ASL or LAK
      cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1994275
TI  - Shunt malfunction and the Rickham reservoir.

PMID- 1994276
TI  - The merits of the antisiphon device.

PMID- 1994277
TI  - Leptomeningeal cyst.

PMID- 1994278
TI  - Immunohistochemical study of erythropoietin in cerebellar hemangioblastomas
      associated with secondary polycythemia.
AB  - Although cerebellar hemangioblastomas are known to be associated with secondary
      polycythemia, the cellular derivation of erythropoietin (EPO) in
      hemangioblastomas still remains obscure. Specimens from 18 patients with
      cerebellar hemangioblastomas were immunohistochemically studied using anti-EPO
      monoclonal antibody. Eight cases of brain tumors, including 2 meningiomas, 2
      medulloblastomas, 2 glioblastomas, and 2 metastatic brain tumors were studied as
      controls. In 9 of 18 cases, EPO-positive cells were scattered around the
      capillaries and were ultrastructurally shown to be mast cells. These cases were
      not, however, associated with secondary polycythemia. In contrast, the stromal
      cells were positive for EPO in 3 cases. Among them, one was associated with
      secondary polycythemia. Furthermore, one-half of the control cases of brain tumor
      contained EPO-positive mast cells. Accordingly, it was suggested that mast cells
      (or small granulocytes) have little relationship to the release of EPO; however,
      some stromal cells might release EPO with a resultant polycythemia.

PMID- 1994279
TI  - A study of the effectiveness of the iron-chelating agent deferoxamine as
      vasospasm prophylaxis in a rabbit model of subarachnoid hemorrhage.
AB  - The pathogenesis of cerebral vasospasm occurring after subarachnoid hemorrhage
      (SAH) is unknown. Several lines of experimentation have suggested a free radical
      mechanism in the etiology of vasospasm. Iron is an important catalyst in the
      generation of free radicals and lipid peroxides in response to tissue injury. We
      hypothesize that the elaboration of iron from the subarachnoid clot might result
      in enhanced generation of free radicals and lipid peroxidation. If so, then
      treatment with deferoxamine, an iron-chelating compound, might reduce the
      formation of free radicals and thereby ameliorate vasospasm. This hypothesis was
      examined in a rabbit model of experimental cerebral vasospasm. New Zealand White
      rabbits were divided into the following experimental groups: control (normal)
      animals (n = 7), control animals treated with deferoxamine (n = 3), animals
      subjected to SAH and killed on Day 2 (n = 7), animals subjected to SAH on Day 2
      and treated with deferoxamine (n = 9), animals subjected to SAH killed on Day 3
      (n = 7), and animals subjected to SAH on Day 3 and treated with deferoxamine (n =
      7). Deferoxamine treatment (50 mg/kg/8 hours) was begun 16 hours before the
      induction of SAH and continued until the animals were killed by perfusion
      fixation. The basilar artery caliber was assessed using morphometric techniques.
      The diameter of the basilar arteries in the control animals was 0.64 +/- 0.02 mm.
      Deferoxamine treatment alone did not alter the artery diameter.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1994280
TI  - Impairment of cerebral autoregulation during the development of chronic cerebral
      vasospasm after subarachnoid hemorrhage in primates.
AB  - We studied the impairment of autoregulation of cerebral blood flow (CBF) and its
      effect on the electrical activity of the brain during the development of chronic
      cerebral vasospasm after subarachnoid hemorrhage, using a vasospasm model in
      primates. Fourteen animals were divided into two groups: a clot group (8) and a
      sham-operated group (6). To induce subarachnoid hemorrhage, all the animals
      underwent craniectomy, and in the clot group, the autologous blood clot was
      located around the arteries dissected free from the arachnoid membrane. Cerebral
      angiography was performed before subarachnoid hemorrhage and 7 days after (Day
      7). On Day 7, regional CBF in the parietal lobe--measured by the hydrogen
      clearance method--and central conduction time were studied during either graded
      hypertension or hypotension. In the clot group, the mean vessel caliber of the
      cerebral arteries on the right side (clot side) of the circle of Willis showed
      significant (P less than 0.01) reduction (more than 40%) as compared with the
      values on the contralateral, non-clot side. The values for the bilateral parietal
      CBF in the sham-operated group and the left parietal CBF in the clot group were
      fairly constant when the mean arterial blood pressure (MABP) was in the range of
      60 to 160 mm Hg. In the clot group, right parietal CBF was significantly (P less
      than 0.05) smaller than that on the left side at an MABP level of 40 to 100 mm
      Hg, and increased at an MABP level of 180 mm Hg. The right parietal CBF increased
      as the arterial blood pressure increased, showing impairment of
      autoregulation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1994281
TI  - Monitoring of cortical blood flow during temporary arterial occlusion in aneurysm
      surgery by the thermal diffusion method.
AB  - During aneurysm surgery, regional cortical blood flow (CoBF) was continuously
      monitored in 12 patients with a thermal diffusion flow probe in an attempt to
      assess the effects of temporary major arterial occlusion on blood flow and
      outcome. When the CoBF was above 30 ml/100 g/min, the safe period for temporary
      clipping applied distal to the perforators was 15 minutes. The occlusion time
      should be shortened when the CoBF is below 30 ml/100 g/min. Two patients suffered
      basal infarction, which was not detected by CoBF monitoring. Attention should be
      paid to the blood flow in the deep structures when a temporary clip is applied at
      a site proximal to the perforating branches. Direct measurement of CoBF may be of
      value in estimating the time that temporary occlusion of a major vessel can be
      tolerated.

PMID- 1994282
TI  - The effect of continuous drainage of cerebrospinal fluid in patients with
      subarachnoid hemorrhage: a retrospective analysis of 108 patients.
AB  - The effects of continuous drainage of cerebrospinal fluid (CSF) on vasospasm and
      hydrocephalus were analyzed retrospectively in 108 patients with subarachnoid
      hemorrhage (SAH) who were operated on for ruptured aneurysms within 48 hours of
      their onset. Ninety-two of these patients underwent a procedure for CSF drainage
      (cisternal drainage, ventricular drainage, lumbar drainage, or a combination of
      these). The duration, the total volume, and the average daily volume of CSF
      drainage were 10.4 +/- 7.0 days (mean +/- SD). 2034 +/- 1566 ml, and 190 +/- 65.3
      ml, respectively. Patients with a greater drainage volume at a lower height of
      drainage in the early period after SAH developed more cerebral infarctions later
      (P less than 0.025). The relationship between the total volume of CSF removed and
      shunt-dependent hydrocephalus was determined to be statistically significant (P
      less than 0.005). Cerebral infarction and hydrocephalus after SAH were also found
      to be statistically associated (P less than 0.001). Thus, continuous
      cerebrospinal fluid drainage should not be performed too readily in patients with
      SAH, because the removal of a large amount of CSF can induce cerebral vasospasm
      as well as hydrocephalus.

PMID- 1994283
TI  - Cavernous malformations and capillary telangiectasia: a spectrum within a single
      pathological entity.
AB  - Cerebral vascular malformations have traditionally been divided into four
      categories: arteriovenous, venous, cavernous, and capillary telangiectases. A
      controversy exists about separating the latter two lesions into separate
      entities. Critics claim the distinction is arbitrary but have been unable to
      present convincing evidence linking the two types of lesions. We have reviewed
      the histories of 20 patients with cavernous malformations and have analyzed the
      clinical, radiographic, and surgical-autopsy data associated with these lesions.
      In some patients, multiple lesions, including cavernous malformations, capillary
      telangiectases, and transitional forms between the two, were identified. Based on
      this analysis, we conclude that capillary telangiectasia and cavernous
      malformations represent two pathological extremes within the same vascular
      malformation category and propose grouping them as a single cerebral entity
      called cerebral capillary malformations.

PMID- 1994284
TI  - Chronic headache associated with a functioning shunt: usefulness of pressure
      monitoring.
AB  - Chronic headaches in a shunt-dependent patient with small ventricles has long
      been treated with little or no regard to intracranial pressure. In this study,
      pressure monitoring on 12 such patients demonstrated that they fell into three
      distinct categories: 3 had headaches caused by intracranial hypertension, 2 had
      headaches from hypotension, and 7 showed no relation of symptoms to pressure. As
      therapeutic procedures for treating these three categories are entirely different
      and sometimes opposing, it is clear that intracranial pressure monitoring is
      essential to successful management of this complaint.

PMID- 1994285
TI  - The Caspar microsurgical discectomy and comparison with a conventional standard
      lumbar disc procedure.
AB  - The outcome in 119 patients who were operated on with a conventional standard
      lumbar discectomy procedure was retrospectively compared with that in 299
      patients who were operated on with a microsurgical discectomy technique developed
      in Homburg/Saar, Federal Republic of Germany by the senior author (W.C.). All
      patients in this consecutive series had "virgin" lumbar radiculopathy evaluated
      and operated upon by two experienced surgeons at one institution. Determination
      of the final outcome was made objectively by an impartial third party using
      identical criteria for both groups, and with a patient self-evaluation form. The
      study looked at various pertinent aspects of the treatment course and at final
      outcome. The results in the microsurgical group were significantly favorable:
      fewer levels were explored: there was less operative blood loss and a decreased
      incidence of deep venous thrombosis, urinary tract infections, pulmonary emboli,
      and bladder catheterization; the time to full ambulation, discharge, and return
      to work was faster: and there was a decrease in change of occupation and a
      greater percentage of satisfactory final outcomes, as measured both objectively
      and subjectively. A description of the microsurgical technique used in this
      study, which differs significantly from existing microdisectomy techniques, is
      presented. The authors conclude that the microsurgical disectomy technique
      presented in this study is a safe and effective approach to the treatment of
      lumbar radiculopathy.

PMID- 1994286
TI  - Disposition of cerebral metastases from malignant melanoma: implications for
      radiosurgery.
AB  - Radiosurgery is becoming more generally available and indications for its use
      continue to be defined. Cerebral metastases from malignant melanoma are often
      treated with whole-brain irradiation, but with limited benefit. Innovative
      treatments, such as radiosurgery, make possible the delivery of doses of
      radiation that are higher than usual. To determine how many patients might be
      candidates for radiosurgery, a retrospective analysis of computed tomographic
      brain scans performed on 41 patients with cerebral metastases from malignant
      melanoma was undertaken. One-third of these patients were found to have cerebral
      metastases amenable to a radiosurgical approach, as illustrated radiation dose
      volume histograms. Patient and tumor characteristics suggest that this series is
      represent with cerebral metastases from malignant melanoma. The implications of
      radiosurgery for normal tissue radiation tolerance and its effects on melanoma
      are discussed.

PMID- 1994287
TI  - The transoral approach for the management of intradural lesions at the
      craniovertebral junction: review of 7 cases.
AB  - The main difficulty in dealing with intradural lesions located ventrally in the
      region of the craniovertebral junction (CVJ) is related to their relative
      inaccessibility. Posterolateral approaches involve some manipulation of the brain
      stem and provide limited access because of the necessity of working between the
      cranial nerves. Even then, the view of the ventral midline and across is limited.
      The transoral approach, which has been widely used for the management of
      extradural lesions in this area, is also useful for the treatment of intradural
      lesions. It provides an unimpeded although somewhat restricted, view of the
      ventral aspect of the CVJ without the need for brain retraction. The cranial
      nerves and vertebral arteries are not interposed between the surgeon and the
      lesion. The risks of cerebrospinal fluid leakage and infection are greatly
      diminished by the use of fibrin adhesive and prolonged diversion of the
      cerebrospinal fluid. The use of this approach, together with its technical
      difficulties and results, in the management of seven purely intradural lesions
      located ventrally at the CVJ, is discussed.

PMID- 1994289
TI  - Nurse policy analyst. Advanced practice role.

PMID- 1994288
TI  - Improved access to lesions of the central skull base by mobilization of the
      zygoma: experience with 54 cases.
AB  - Improved access to lesions at the medial end of the sphenoid wing or in the
      interpeduncular cistern after mobilization of the zygoma has been a subject of
      growing interest in recent years. This study describes the operative technique we
      have adopted and records our experience with 55 operations in 54 patients who
      underwent the procedure in the past 3 years. Seven patients had vascular lesions,
      44 had tumors, and 3 had miscellaneous lesions. The majority of the tumors were
      medial meningiomas, and particular note is made of those arising from the
      cavernous sinus with respect to their resectability. Sixteen of these tumors were
      encountered, and total excision was possible in 11 cases. Access to the
      infratemporal fossa is facilitated, and in 2 cases we were able to excise
      completely trigeminal neuromas that had extended there. The extra maneuver adds
      little to the overall operating time, and complications relating to it are
      uncommon, mild in degree, and usually self-limiting. We conclude that the
      operation is extremely valuable in appropriate circumstances.

PMID- 1994290
TI  - Public policy: new opportunities for nurses.

PMID- 1994291
TI  - An interview with America's highest-ranking nurse, O. Marie Henry. Interview by
      Barbara J. Barnum.

PMID- 1994292
TI  - Health care under siege: challenge for change.

PMID- 1994293
TI  - Whither nursing?

PMID- 1994294
TI  - Model for integrating health services research and health care policy formation.

PMID- 1994296
TI  - Compatibility.

PMID- 1994295
TI  - Associate Degree Nursing Programs accredited by the NLN 1989-90.

PMID- 1994297
TI  - AIDS: advocacy and activism.

PMID- 1994298
TI  - Physician training in the recognition and reporting of child abuse, maltreatment,
      and neglect.

PMID- 1994299
TI  - The Great War: its impact on the British and American medical communities, 1914
      1918.

PMID- 1994300
TI  - Autoimmune paraneoplastic diseases of the nervous system.

PMID- 1994301
TI  - Myasthenic (Eaton-Lambert) syndrome in association with an indolent non-Hodgkin's
      lymphoma.

PMID- 1994302
TI  - Primary pedunculated leiomyosarcoma of the lung.

PMID- 1994303
TI  - Severe hypokalemia and ventilator-dependent, generalized paralysis.

PMID- 1994304
TI  - Isolated common iliac artery aneurysm.

PMID- 1994306
TI  - Ray Brook State Tuberculosis Hospital.

PMID- 1994305
TI  - Systemic sclerosis possibly caused by 5-fluorouracil.

PMID- 1994307
TI  - Dressler's syndrome and facial paralysis.

PMID- 1994308
TI  - Fatal pneumococcal infection: another plea for the pneumococcal vaccine.

PMID- 1994309
TI  - Percutaneous catheter drainage for acute empyema. Improved cure rate using CAT
      scan, fluoroscopy, and pigtail drainage catheters.
AB  - Percutaneously inserted pigtail nephrostomy catheters were used to treat empyemas
      in 12 patients. Thoracic computed tomographic (CT) scan and fluoroscopy were used
      to localize precisely and place the catheters into loculated collections of
      fluid. Percutaneous catheter drainage (PCD) of empyema was successful in seven of
      seven patients (100%) in whom standard tube thoracostomy (STT) had initially
      failed and in three of five patients (60%) who had PCD as the initial drainage
      procedure. Overall, PCD was successful in treating empyema in ten of 12 patients
      (83%). The procedure was well tolerated and there were no complications. PCD is a
      safe and effective method for drainage of loculated empyemas as the initial
      procedure or after STT has failed.

PMID- 1994310
TI  - Actinomyces organisms associated with a tooth intentionally reimplanted two years
      previously. A case report.

PMID- 1994311
TI  - Location of abnormalities in panoramic radiographs of edentulous patients.
AB  - A series of 308 panoramic radiographs of edentulous patients was examined for the
      presence of pathoses to determine whether any predictive basis could be found for
      occurrence of abnormalities by sex, age, or location. Radiolucencies,
      radiopacities, and retained roots and teeth were recorded by size and by anterior
      or posterior location in edentulous jaws. Radiopacities were the most frequently
      found abnormality (18% of subjects), followed by retained roots (8%),
      radiolucencies (3%), and retained teeth (3%). No significant correlation was
      found by chi-square test between type or location of abnormality and sex of the
      patient. There was, however, a significant relationship between location and type
      of abnormality. Radiopaque and radiolucent lesions were more frequently found in
      the mandible, and unerupted teeth and retained roots were more frequently seen in
      the posterior maxilla. Selective radiographs to detect retained roots and
      unerupted teeth in the posterior maxilla may be most productive in terms of
      prosthodontic treatment outcome. Otherwise, this study finds no basis for
      selection of intraoral sites for specific intraoral radiographs of asymptomatic
      edentulous patients.

PMID- 1994312
TI  - Studies on focal alveolar bone healing with technetium (Tc)-99m labeled methylene
      diphosphonate and gold-collimated cadmium telluride probe.
AB  - The benefit of using a collimator for a miniaturized cadmium telluride probe was
      evaluated by monitoring the bone-healing processes for 13 weeks after the
      induction of small iatrogenic alveolar bone lesions in one side of the mandible
      in beagles. Technetium (Tc)-99m labeled methylene diphosphonate (200 to 300 MBq,
      5.1 to 8.1 mCi, in a solution of 0.5 to 1 ml, intravenously) was used as a bone
      seeking radiopharmaceutical. The radioactivity over the bone lesion (L) and the
      contralateral normal site (C) in the mandible were measured between 1.5 and 2
      hours after injection of the tracer, and the activity ratio L/C served as an
      index of relative bone uptake. A study of six dogs revealed that the healing
      response to a hemispheric bone defect of 2 mm diameter in the cortical bone could
      not be detected by an uncollimated probe, and in a repeated study in two dogs the
      use of a gold collimator (5 mm in diameter, 5 mm in length) did not increase the
      L/C ratio significantly. A second study in six dogs with 5 mm lesions showed that
      although systematic trends in the time courses of the L/C ratio obtained both
      with and without the collimator could be demonstrated, the L/C ratio of
      collimated versus uncollimated measurements was significantly (p less than 0.005)
      increased. In three of the latter six dogs, abscesses developed after 9 weeks,
      leading to a second increase (p less than 0.05) of the L/C ratio with collimation
      compared with the noninflammation group; without collimation no significant (p
      greater than 0.15) difference between the two groups could be
      demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1994313
TI  - Chairside disinfection of radiographs.
AB  - Routine disinfection of materials that have contacted human blood products and
      body fluids during patient care is recommended by the American Dental Association
      and the Centers for Disease Control. The purpose of this study was to determine
      whether surface disinfection with sodium hypochlorite would be an effective means
      for disinfection of radiographic film packets used in chairside developers.
      Disinfection of exposed radiographic film packets for 30 seconds in 5.25% sodium
      hypochlorite has been found to be a simple procedure suitable for routine use. A
      suggested disinfection protocol for the use of chairside developing boxes is
      described. This procedure should be considered for adoption as an infection
      control guideline.

PMID- 1994314
TI  - Automatic processing: effects of temperature and time changes on sensitometric
      properties of ULTRA-SPEED and EKTASPEED films.
AB  - The effects of changes in the processing temperature and time of automatic
      processors were studied with Kodak ULTRA-SPEED and EKTASPEED dental x-ray films.
      Speeds and inherent contrasts were derived for the two films from sensitometric
      curves at seven different temperatures and at five different processing times. As
      opposed to manual processing, only a slight change in film fog was observed with
      increases in automatic processing temperature or time. Film speed and contrast
      could be increased by increasing the processing temperature or time. The
      EKTASPEED film was more sensitive to these changes than was the ULTRA-SPEED film.
      Temperature had a stronger influence than processing time. All films were of
      archival storage quality except those processed at the low processing times of
      2.5 or 3.5 minutes, and at the low processing temperature of 21 degrees C.

PMID- 1994315
TI  - Radiographic diagnosis of developmental mandibular hypofunction.

PMID- 1994316
TI  - Inhalation of dental prosthesis.

PMID- 1994317
TI  - Artifactual foreign body.

PMID- 1994318
TI  - Inhalation of an avulsed primary tooth.

PMID- 1994319
TI  - Submandibular cystic hygroma resembling a plunging ranula in a neonate. Review
      and report of a case.
AB  - Cystic hygromas are large lymphangiomas that are most often found in the
      posterior triangle of the neck and the axilla in children. They are most
      frequently found before age 2 and may be massive. After upper respiratory
      infection, they may become infected and enlarged, causing dysphagia and toxemia.
      The diagnosis can usually be made by history and physical examination and
      confirmed by biopsy. Treatment is by surgical excision of small lesions and
      staged debulking excisions in more severe cases. A patient with a cystic hygroma
      having many clinical characteristics of a plunging ranula is presented. The cyst
      fluid was aspirated and analyzed for its amylase, sodium, potassium, chloride,
      urea nitrogen, glucose, and total protein content. The characteristics of the
      fluid were also compared with those of lymph and saliva. This report demonstrates
      the difficulty in determining the diagnosis of a tumor that has the clinical
      features of a cystic hygroma, as well as a plunging ranula. The necessity of a
      proper presurgical diagnosis is essential since the form of therapy for each is
      different and conflicting. A method that distinguishes between the cervical
      cystic hygroma and a plunging ranula by means of aspirated fluid is discussed.

PMID- 1994320
TI  - Guidelines for intraoperative monitoring of dental patients undergoing conscious
      sedation, deep sedation, and general anesthesia.
AB  - The promulgation and adoption of intraoperative monitoring standards in medicine
      for anesthesia has resulted in early detection of untoward events during sedation
      and anesthesia, lowering of malpractice premiums, and an improvement in the
      quality of care. The American Dental Society of Anesthesiology has devised
      specific, detailed monitoring standards with universal applicability in the
      dental setting.

PMID- 1994321
TI  - Treatment of refractory oral candidiasis with fluconazole. A case report.
AB  - We describe a patient with the acquired immunodeficiency syndrome who had
      persistent oral esophageal pseudomembranous candidiasis clinically refractory to
      nystatin, clotrimazole, and ketoconazole. In vitro resistance to clotrimazole was
      demonstrated as well. The patient received temporary relief with intravenous
      amphotericin B therapy, but this was associated with serious adverse effects,
      including transfusion-requiring anemia, azotemia, and severe thrombophlebitis.
      Despite two courses of intravenous amphotericin B therapy, the patient's highly
      symptomatic, recurrent oral and esophageal candidiasis continued. The patient was
      then treated with fluconazole and obtained immediate relief without associated
      adverse effects.

PMID- 1994322
TI  - Effect of antileukemia chemotherapy on marrow, blood, and oral granulocyte
      counts.
AB  - This study was designed to elicit the effects of antileukemia chemotherapy on
      marrow production, blood carriage, and oral extravasation of granulocytes, and on
      the phagocytic activity of those harvested from the mouth. Fifteen adult patients
      with various morphologic forms of acute leukemia were followed through one to
      four courses of chemotherapy. Oral saline rinse samples were obtained thrice
      weekly and prepared for enumeration in a hemocytometer. The oral granulocyte
      counts were compared with concurrent counts in the bone marrow and peripheral
      blood. Phagocytic activity of the oral granulocytes was measured by the method of
      Smith and Rommel. The 15 patients were followed through 30 courses of
      chemotherapy and recovery. During each, there was a drug-induced decrease in
      marrow, blood, and oral granulocytes that was reversed when therapy was
      discontinued and bone marrow activity was restored. Phagocytic activity of the
      oral granulocytes was not perceptibly affected by the antileukemic drugs. Oral
      granulocyte counts provide a noninvasive method for monitoring the onset and
      recovery of chemotherapy-induced myelosuppression and granulocytopenia in
      patients with leukemia.

PMID- 1994323
TI  - Gingival swelling as a manifestation of aplastic anemia.
AB  - Gingivitis in the preschool child is uncommon and is usually associated with
      underlying systemic disease such as leukemias, neutropenias, and other
      immunologic defects. This report describes gingival hyperplasia in a preschool
      child with aplastic anemia and highlights the need to exclude systemic disease in
      children with periodontal disease.

PMID- 1994324
TI  - Melanocytic hyperplasia of the oral mucosa.
AB  - Lesions that exhibit melanocytic hyperplasia are uncommon in the oral mucosa.
      They are even more rare than the various morphologic types of nevomelanocytic
      lesions. This article reports the clinicopathologic features of oral lesions
      diagnosed as lentigo simplex, junctional lentigo ("jentigo"), atypical
      melanocytic hyperplasia (melanoma in situ), and melanocanthoma. The proper
      terminology for these lesions is also discussed.

PMID- 1994325
TI  - Enamel pitting: a common symptom of tuberous sclerosis.
AB  - Dental enamel pitting as a diagnostic sign of tuberous sclerosis is explored, and
      a protocol for the oral examination of patients and persons at risk is described.
      In this study 50 patients with tuberous sclerosis and 250 control patients were
      examined for dental enamel pitting. A simple clinical protocol was established
      for examination with the use of a dental disclosing solution swabbed on dry
      teeth. The incidence of enamel pitting in the adult dentition of patients with
      tuberous sclerosis was 100%, whereas that in the adult dentition of the control
      group was 7%. The simplicity of the test and the high probability of occurrence
      in tuberous sclerosis make such an examination useful in the diagnosis of this
      serious genetic disease.

PMID- 1994326
TI  - Major aphthous-like ulcers in patients with AIDS.
AB  - This report describes persistent, painful oral ulcers that occurred in nine
      patients with the acquired immunodeficiency syndrome (AIDS). These ulcers
      resembled major aphthous ulcers in clinical appearance and response to therapy.
      They occurred less frequently in patients with AIDS than those caused by herpes
      simplex and were found in 4 of 346 (1.1%) patients with AIDS at one medical
      center. Lesions were typically painful. Identification and treatment with topical
      tetracycline and steroids led to resolution with relief of symptoms. Further
      study is necessary to understand the etiology and pathogenesis of these ulcers.

PMID- 1994327
TI  - Ectopic thyroid tissue in the submandibular region.
AB  - This report describes an unusual location of ectopic thyroid gland tissue. A
      growth in the left submandibular area was surgically excised, and the microscopic
      examination of the specimen revealed thyroid tissue with colloid goiter. Because
      this entity cannot be clinically distinguished from a salivary gland tumor,
      ectopic thyroid tissue should be considered in the differential diagnosis of
      swellings involving the submandibular area.

PMID- 1994328
TI  - Orofacial metastasis of pulmonary giant cell carcinoma.
AB  - A patient was admitted to the hospital with multiple skin nodules of recent
      origin and signs and symptoms suggestive of acute pulmonary infection. Because
      one of the skin masses was located overlying the left mandibular body region, the
      patient was referred to the hospital dentistry clinic for evaluation. Historical,
      clinical, and radiographic assessments were consistent with reactive
      lymphadenopathy, and an intraoral excisional biopsy was performed. The biopsy
      results were indicative of giant cell carcinoma, which was confirmed by biopsy
      results from a similar skin lesion on the shoulder and by malignant cells
      recovered in the sputum and pleural fluids. Although this carcinoma has been
      shown to rarely metastasize to the skin and lymphatics of the neck, this is the
      first case report of metastasis to facial lymphatics.

PMID- 1994329
TI  - Blue rubber bleb nevus syndrome with oral hemangiomas.
AB  - A case of blue rubber bleb nevus syndrome with oral hemangiomas is reported.
      Attention is directed to this syndrome because, although rare, it is usually
      associated with oral lesions. The blue rubber bleb nevus syndrome should always
      be considered a possibility in patients with oral hemangiomas and bluish skin
      nodules.

PMID- 1994330
TI  - Nonionizing method of locating the apical constriction (minor foramen) in root
      canals.
AB  - The electronic method was evaluated as to its accuracy when used to determine the
      position of the apical constriction (minor foramen) in root canals. There were 39
      vital and 8 nonvital teeth for a total of 47 specimens from 22 patients. The
      specimens were prepared with a Buehler Isomet bone saw to a thickness of 500
      microns. Distances were measured and recorded with the use of a Bioquant II image
      analysis system. The electronic method appeared to measure a mean value of 0.2 mm
      coronal to the cemetodentinal junction in 47 canals where the apex locator was
      set at a reference setting of 40. When a frequency curve was plotted, it showed
      that the probability of being within 0.76 mm (1 SD) of the cementodentinal
      junction was 68%. This appears to correlate to where Kuttler indicated the minor
      constriction to be located. These devices seem to offer a unique method to locate
      the apical constriction and thus to ensure proper working length while reducing
      ionizing radiation.

PMID- 1994331
TI  - [A new law makes it possible: the caregiver as psychotherapist].

PMID- 1994332
TI  - [Care of people with AIDS at the 1st. Viennese University Dermatology
      Department].

PMID- 1994333
TI  - [Nursing at the university. International conference of institutes for the
      continuing education of administrative and teaching nursing personnel].

PMID- 1994334
TI  - [Everyday activities of an occupational medical assistant].

PMID- 1994335
TI  - The new epidemic: chronic fatigue syndrome.

PMID- 1994336
TI  - Survey on nursing practice HIV-infected/AIDS patients' responses.

PMID- 1994338
TI  - Gulf war. On standby for action.

PMID- 1994337
TI  - War wounds. Interview by Toni Turner.

PMID- 1994339
TI  - Shut out.

PMID- 1994341
TI  - Body politic. The first casualty.

PMID- 1994340
TI  - Conceptive pill?

PMID- 1994342
TI  - Hepatitis B. Who is at risk?

PMID- 1994343
TI  - Hepatitis B. Test your knowledge.

PMID- 1994344
TI  - Unwilling guests.

PMID- 1994345
TI  - LA flaw.

PMID- 1994346
TI  - Understanding schizophrenia.

PMID- 1994347
TI  - Cervical cancer. A survivor remembers.

PMID- 1994348
TI  - Cervical cancer. A delicate matter.

PMID- 1994349
TI  - Maintaining a high profile.

PMID- 1994351
TI  - Management. Hitting back.

PMID- 1994350
TI  - Management. Up to date, but out of touch.

PMID- 1994352
TI  - On the road. Wheel basics.

PMID- 1994353
TI  - Taking care of Kathy.

PMID- 1994354
TI  - I'll pass: why being team physician is not for me.

PMID- 1994356
TI  - What to do when results of a western blot test are indeterminate.
AB  - The role of primary care physicians in diagnosis of human immunodeficiency virus
      (HIV) infection is becoming increasingly important. Given the development of
      antiretroviral therapy, which can delay the clinical progression of asymptomatic
      HIV infection, early and accurate identification is invaluable to these patients.
      Screening begins with the enzyme immunoassay, which, although highly sensitive,
      lacks specificity. Therefore, the Western blot test should always be used for
      confirmation. When results of the Western blot test are indeterminate,
      reassessment for risk factors for HIV infection should be followed by serial
      Western blot testing and HIV culture or polymerase chain reaction testing.

PMID- 1994355
TI  - HIV infection in healthcare workers. How great is the risk? What can be done
      before and after exposure?
AB  - Healthcare workers know that there is a risk of HIV infection through exposure to
      AIDS patients. In both hospital and office settings, physicians have the
      opportunity to set standards and promote education about the degree of risk,
      effective precautions, and postexposure testing, prophylaxis, and treatment. Drs
      Henry and Thurn share the latest findings and offer policy recommendations based
      on their own experience.

PMID- 1994357
TI  - AIDS and adolescents. How can you help them reduce their risk?
AB  - AIDS in adolescents (0.4% of all cases) is a problem of increasing importance in
      the United States. Infection with the human immunodeficiency virus (HIV) exists
      in high schools and on university campuses, and it presents a real and immediate
      threat to teenaged Americans who engage in drug abuse and sexual activity.
      Appropriately targeted educational efforts are needed to limit HIV transmission
      among adolescents. Most adolescents are aware of the high-risk activities that
      may lead to HIV transmission. However, only about one third alter their sexual
      behavior to avoid AIDS. It is important to move beyond imparting knowledge about
      AIDS transmission and to move toward changing risky behavior. Strategies for AIDS
      risk reduction in adolescents should be implemented now across the country.
      Appropriate support and intervention are urgently needed for adolescents at high
      risk.

PMID- 1994358
TI  - Early diagnosis of breast cancer. Universal screening is essential.
AB  - Breast cancer strikes 1 in 10 women in the United States. Early diagnosis of
      breast cancer improves chances of survival. With universal screening and expert
      evaluation of early clinical signs and symptoms of breast cancer, mortality rates
      can be reduced by 30% to 40%. Physicians can help achieve this goal by taking an
      active role in patient education and promoting the availability of affordable
      screening mammography.

PMID- 1994359
TI  - Nipple discharge in women. Is it cause for concern?
AB  - Nipple discharge is one of the most common breast complaints in women.
      Galactorrhea (milky discharge) may occur during pregnancy or breast-feeding or as
      a result of drug therapy, hypothyroidism, or hyperthyroidism. Nonbloody discharge
      is most common and is usually benign. Bloody discharge should be considered a
      sign of cancer until proved otherwise. Persistent galactorrhea and nonbloody
      discharge can be treated by transecting the mammary ducts. Simple mastectomy may
      be appropriate in patients with persistent bloody discharge who have a strong
      family history of breast cancer.

PMID- 1994360
TI  - Options for painless local anesthesia.
AB  - Fear of the needle is a real issue with some patients and may be an obstacle to
      inducing anesthesia before minor surgical procedures are performed. Adults may
      express this fear verbally or, out of embarrassment, even avoid coming to the
      physician's office. Children may become intensely anxious and hysterical. In this
      article, Dr Holmes describes the use of alternative procedures and agents for
      reducing the pain of inducing anesthesia and thus reducing patients' anxiety.

PMID- 1994362
TI  - Depression after acute myocardial infarction. The role of primary care physicians
      in rehabilitation.
AB  - Depression is a common problem after myocardial infarction. Diagnosis is
      facilitated by use of the criteria for depression in the Diagnostic and
      Statistical Manual of Mental Disorders and self-rating questionnaires. Treatment
      may involve both psychological and pharmacologic interventions. The patient's
      medical status must be carefully assessed before administration of antidepressant
      medication. All antidepressants are contraindicated immediately after myocardial
      infarction. When signs and symptoms of depression are exhibited early in the
      recovery phase, alprazolam (Xanax) may offer advantages over more traditional
      antidepressants. Further research is necessary to determine the safety of newer
      antidepressants.

PMID- 1994361
TI  - Donating a kidney to a family member. How primary care physicians can help
      prepare potential donors.
AB  - When a relative needs a kidney to survive, family members often impulsively offer
      to donate one without stopping to consider the physical, emotional, and financial
      ramifications, which can be considerable. The family's primary care physician can
      be very helpful in guiding and educating potential donors and, by arranging for
      screening to be done in the community, can ease the financial strain. The authors
      discuss the things a potential kidney donor should consider.

PMID- 1994363
TI  - Diabetic amyotrophy without pain. A puzzling clinical picture.
AB  - A patient with weight loss and weakness presents a diagnostic challenge. Drs
      Moeser and Kent describe an unusual case of diabetic amyotrophy that required
      extensive workup to arrive at the diagnosis and rule out more serious disease.
      Symptoms were dramatic, and recovery was spontaneous following conservative
      treatment.

PMID- 1994364
TI  - Acts of kindness.

PMID- 1994366
TI  - Development of Trypanosoma fallisi in the leech, Desserobdella picta, in toads
      (Bufo americanus), and in vitro. A light and electron microscopic study.
AB  - The development of Trypanosoma fallisi of Bufo americanus from Algonquin Park,
      Ontario was studied by light and electron microscopy in blood culture, in its
      leech vector Desserobdella (= Batracobdella) picta, and in its toad host. In
      culture, bloodstream trypomastigotes transformed within one day to elongate
      epimastigotes which divided into rosettes. These gave rise to amastigotes,
      spheromastigotes, stumpy and elongate epimastigotes, and slender metacyclic
      trypomastigotes over a 4- to 6-day period. Development in the leech crop was
      similar to that in culture, with fewer amastigotes and no spheromastigotes
      observed. The stages in the leech were similar in size to their culture
      counterparts, except for metacyclic trypomastigotes, which were larger in
      culture. Culture and leech stages possessed a well developed cytostome
      cytopharyngeal complex and prominent reservosomes. The kinetoplast of crop stages
      was small with a rectangular profile, but became larger and basket-like in the
      proboscis forms. Migration of trypanosomes to the proboscis appeared to depend on
      the rate of digestion of the bloodmeal. Flagellates in the leech were also
      characterized by the presence of intracellular microorganisms. Development of
      culture forms to mature stages in the toad was completed within 8 days
      postinoculation, with the organisms transforming into the typical "C"-shape with
      a large square kinetoplast. Natural infection of B. americanus was detected at 3
      days postfeeding by D. picta and the resulting bloodstream trypomastigotes
      developed more slowly than inoculated cultured stages.

PMID- 1994365
TI  - The effect of isometamidium chloride on insect forms of drug-sensitive and drug
      resistant stocks of Trypanosoma vivax: studies in vitro and in tsetse flies.
AB  - Isometamidium chloride-resistant and -sensitive Trypanosoma vivax insect forms
      were continuously propagated in vitro without feeder-layer cells in a semi
      defined liquid medium at 27 degrees C. The effect of isometamidium chloride
      (Samorin) on T. vivax was assessed by monitoring the viability of epimastigotes
      and the production of metacyclic forms. Populations of insect forms of T. vivax
      stock IL 1392 and clone IL 3185 showed reduced growth and died after 10 days when
      cultivated in the presence of 1 ng/ml isometamidium chloride and after 6 days in
      the presence of 10 ng/ml. In contrast, populations of the isometamidium-resistant
      T. vivax stocks CP 2171 and CP 2331 continued to grow for 17 days in the presence
      of 1 ng/ml isometamidium chloride. The production of metacyclics was inhibited in
      cultures of T. vivax IL 1392 after incubation in medium containing 1 or 10 ng/ml
      isometamidium chloride. Epimastigotes of T. vivax CP 2171 and CP 2331 produced
      metacyclic forms in the presence of 1 ng/ml isometamidium chloride but not 10
      ng/ml. When tsetse infected with drug-sensitive T. vivax IL 1392 were fed on a
      Boran steer that had previously been treated with 1 mg/kg isometamidium chloride,
      trypanosome infection rates were greatly reduced. In contrast, infection rates in
      Glossina morsitans centralis infected with drug-resistant T. vivax CP 2171 were
      not affected when these flies were fed on the same drug-treated animal.

PMID- 1994368
TI  - Cytological and immunological responses to Babesia divergens in different hosts:
      ox, gerbil, man.
AB  - A continuous in vitro culture system for Babesia divergens was initiated from a
      human isolate. It was maintained through 305 subcultures for 3 years using a low
      concentration of serum and a low haematocrit, with no decrease in the initial
      virulence. This in vitro system enabled the routine culture of all human and
      bovine B. divergens isolates thus far tested, with a mean parasitaemia level of
      30%-40%. Different cytological aspects observed in the same isolate by optical
      and electron microscopy were described in parasitized ox, gerbil and human
      erythrocytes. The sequence of B. divergens antibody responses was determined in
      man and ox, enabling the precise identification of major B. divergens antigens as
      candidates for vaccines.

PMID- 1994367
TI  - Studies on Pf155/RESA and other soluble antigens from in vitro cultured
      Plasmodium falciparum.
AB  - Spent culture medium from in vitro cultures of Plasmodium falciparum was used as
      the source for immunoadsorbent enrichment of soluble parasite antigens. IgG
      obtained from P. falciparum-hyperimmune Liberian serum was used as the ligand in
      the immunoadsorbent. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      (SDS-PAGE) of the immunoadsorbent isolated material revealed the presence of at
      least 15 antigenic and parasite-derived polypeptides. Immunoblotting after SDS
      PAGE showed greater than 20 antigenic polypeptides in the molecular weight range
      of 15-250 kDa. Several of these were heat-stable (100 degrees C for 5 min), and
      six of them were detected even after heating for 60 min. Among the latter
      antigens was Pf155/RESA, a merozoite antigen deposited in the erythrocyte
      membrane at invasion. Pf155/RESA can be detected using a modified erythrocyte
      membrane immunofluorescence (EMIF) assay. Inhibition of EMIF with heated parasite
      material showed that the antigenic activity was intact after heating for up to 30
      min. The immunofluorescence-inhibitory activity was separated into two fractions,
      one containing Pf155/RESA and one containing polypeptides with molecular weights
      of 135 and 120 kDa. All three of these antigenic polypeptides bound selectively,
      albeit nonspecifically, to aminoethyl-BioGel resins.

PMID- 1994369
TI  - A new photometric assay for testing trypanocidal activity in vitro.
AB  - A new in vitro test was developed to assess the trypanocidal activity of
      compounds against axenically grown Trypanosoma brucei bloodstream forms.
      Trypanosomes from continuous culture were exposed to series of drug dilutions in
      a microtiter plate. After an incubation time of 72 h at 37 degrees C, the pH
      indicator of the medium had changed its colour in non-inhibited cultures due to
      the production of pyruvate. Inhibited cultures showed less, if any, colour
      changes. Plates could be read by eye or using an enzyme-linked immunosorbent
      assay (ELISA) reader. Within the pH range of 7.0-7.5, the extinction values of
      phenol red at 560 nm showed a linear correlation with both the pH of the medium
      and the pyruvate concentration in the medium. By comparison of the decreases in
      extinction in test cultures with those in control cultures, IC50 values (drug
      concentrations causing 50% inhibition) could be determined. Minimal inhibitory
      concentrations (MICs) could be read by eye. The photometric test evaluation was
      compared with evaluation according to growth inhibition or to incorporation of
      radiolabelled hypoxanthine. The three methods of evaluation gave similar results.

PMID- 1994370
TI  - Effect of polyclonal anti-procyclic antibodies on development of Trypanosoma
      brucei brucei in tsetse flies.
AB  - Results obtained in experiments testing the efficacy of anti-procyclic-form
      rabbit sera on the development of homologous and heterologous stocks of
      Trypanosoma brucei brucei in Glossina morsitans morsitans indicated that this
      development was affected little, or not at all, by such sera. The absence of
      effect of anti-procyclic stage antibodies can be explained by the failure to
      detect by either direct or indirect fluorescent antibody methods the presence of
      antibodies acquired in vivo by either the midgut procyclic forms or by uncoated
      salivary gland forms.

PMID- 1994371
TI  - Studies on the screwworm fly Cochliomyia hominivorax in Libya: effect of
      temperature on pupation and eclosion.
AB  - The American screwworm fly Cochliomyia hominivorax has recently been reported in
      Libya (El-Azazy 1989). Fly larvae were cultured on blood agar at different
      temperatures (-5 degrees, 5 degrees, 18 degrees, 20 degrees, 30 degrees, 37
      degrees, or 40 degrees C). Larvae pupated at 18 degrees, 20 degrees, 30 degrees,
      or 37 degrees C, and the highest pupation (100%) occurred at 20 degrees C. Adult
      flies emerged from pupae that were maintained at 18 degrees, 20 degrees, 30
      degrees, or 37 degrees C; the maximal eclosion (94%) occurred at 20 degrees C.
      Correlation of these findings with meteorological temperature data from local
      areas in which C. hominivorax myiasis occurs suggests a crucial role for
      temperature in the determination of the effective environment for this fly
      species.

PMID- 1994372
TI  - The effect of ecdysteroids on the microfilarial production of Brugia pahangi and
      the control of meiotic reinitiation in the oocytes of Dirofilaria immitis.
AB  - The effects of the ecdysteroids ecdysone and 20-hydroxyecdysone on microfilarial
      release in Brugia pahangi and on meiotic reinitiation in the oocytes of
      Dirofilaria immitis were studied. Ecdysone was found to stimulate microfilarial
      release at 2 x 10(-6) M, but this effect was reduced at higher and lower
      concentrations. 20-Hydroxyecdysone was found to have no such effect. In D.
      immitis, ecdysone at 10(-5) M was also found to overcome the period of meiotic
      arrest that occurs during the pachytene stage of prophase 1. This effect was
      reduced when 10(-6) M ecdysone was used. These results help support the theory
      that the ecdysteroids play a hormonal role in filarial worms similar to that
      found in insects.

PMID- 1994373
TI  - A light and electron microscope study on in vitro excystation of Microphallus
      abortivus (Digenea: Microphallidae) metacercariae.

PMID- 1994374
TI  - Bioenergetics in a parasitic nematode, Steinernema carpocapsae, monitored in vivo
      by flow NMR spectroscopy.

PMID- 1994375
TI  - Testosterone biotransformation by the isolated perfused canine pancreas.
AB  - There is strong evidence indicating that the pancreas is under the influence of
      sex steroid hormones, and that it may even participate in their biosynthesis and
      metabolism. In the present study, [3H]testosterone was perfused into the isolated
      canine pancreas, and measured in the effluent with several of its metabolites (5
      alpha-dihydrotestosterone, androstenedione, and estradiol). Results show that
      testosterone is readily transformed by the canine pancreas. The main product
      found in the effluent is androstenedione. The testis and spleen were also
      perfused with [3H]testosterone and used as controls. In both cases, this hormone
      appeared mostly unchanged in the effluent as compared to the pancreatic perfusion
      (p less than 0.0001). From our data, we conclude that the canine pancreas has the
      capacity to transform sex steroid hormones, and could be considered an
      extragonadal site of sex steroid biosynthesis.

PMID- 1994376
TI  - Malignant T-cell lymphoma of the pancreas.
AB  - A case of malignant T-cell lymphoma of the pancreas is presented. Previously
      reported histological data confirming this disease are reviewed to elucidate
      features that may suggest this disease and how to differentiate between T- and B
      cell lymphoma of the pancreas.

PMID- 1994377
TI  - Mucinous ductal ectasia of the pancreas: a premalignant disease and a cause of
      obstructive pancreatitis.
AB  - Five cases of localized ectasiae of pancreatic ducts associated with epithelial
      mucinous metaplasia have been previously reported by Itai et al. (Radiology 1986;
      161:697-700). During a 1-year period, we collected four new observations of
      patients presenting with recurrent attacks of pancreatic pain due to similar
      clusters of cystlike dilated ducts communicating with the main pancreatic duct
      and lined by a columnar epithelium interspersed with numerous goblet cells. Duct
      lumina were filled with mucous. Carcinoembryonic antigen levels were high in the
      pure pancreatic juice, but normal in the blood. Sonography and CT scan showed
      cystlike, intrapancreatic defects localized three times in the head of the
      pancreas and once in the body. Endoscopic retrograde cholangiopancreatography
      (ERCP) showed a huge dilation of some collateral ducts filled by radiolucent
      defects. The main pancreatic duct was dilated proximally to pathological ducts in
      three cases. Neither pancreatic stones nor exocrine insufficiency could be
      demonstrated 7 years after the clinical onset; one case presented with an in situ
      carcinoma. Since mucinous ductal ectasia is a precancerous state, surgery is
      mandatory. ERCP is probably the best method of diagnosis.

PMID- 1994378
TI  - Expression of fetoacinar pancreatic (FAP) protein in the pancreatic human tumor
      cell line BxPC-3.
AB  - Fetoacinar pancreatic (FAP) protein is a specific component of the human exocrine
      pancreas that may have a role in the differentiation and transformation of this
      organ. In order to set out a model for studies on the regulation of FAP, 47
      established cell lines from human cancer of different origins were tested for FAP
      expression using the monoclonal antibody J28 (Mab J28). Only two, both
      pancreatic, were positive. This finding supports the already reported pancreatic
      specificity of this antigen. Strongest expression was shown by the BxPC-3 cell
      line, derived from a moderately well-differentiated adenocarcinoma in the body of
      the pancreas. In BxPC-3 cells grown in Roswell Park Memorial Institute (RPMI)
      1640-10% fetal bovine serum (FBS), Mab J28 immunostaining was localized in the
      cytoplasm of the cells. In serum-free medium, cells quickly died. Growth and FAP
      expression were maintained when this medium was supplemented with insulin. FAP is
      not released to the culture medium, as evidence by absence of reaction with the
      monoclonal antibody on nitrocellulose dot-blots. On the contrary, a positive
      reaction was observed in cell homogenates made by sonication or by extraction
      with 0.1% Triton. A competitive enzyme-linked immunosorbent assay (ELISA), using
      biotinylated FAP, was developed to quantify the protein in cell homogenates.
      Concentrations of FAP in homogenates from cells cultured in standard conditions
      or serum-free supplemented with insulin were in the range of 0.28-0.40 micrograms
      FAP/mg total protein.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1994379
TI  - Insulin-sparing effects of pancreatic polypeptide in congenitally obese rodents.
AB  - Chronic treatment with bovine pancreatic polypeptide (bPP) is reported to
      decrease body weight and reduce fasting glucose and insulin concentrations in
      congenitally obese mice. The present study examines the effects of acute and
      chronic bPP treatment on insulin release and glucose clearance in lean and obese
      rodents. After single injections of 0, 5, 50, or 500 micrograms of bPP/kg of body
      weight, the insulin response to an intragastric glucose meal (5 g/kg of body
      weight) was substantially inhibited by the two higher doses of bPP. The change in
      glucose concentration over time was similar among all animals except those
      receiving the highest dose of bPP (500 micrograms/kg of body weight); in this
      group, glucose rose to higher levels and was slower to return to basal levels.
      Chronic treatment of rats with 200 micrograms of bPP/day/kg of body weight for 5
      days did not modify glucose or insulin responses to the glucose meal, but did
      increase the activity of hepatic glycogen synthetase. In contrast, basal glucose
      levels were lower in obese mice (ob/ob) treated with bPP and glucose clearance
      was improved in the treated group after injection of exogenous insulin. Islet
      hormone concentrations in pancreatic extracts were compared in lean and obese
      mice treated with and without 200 micrograms of bPP/day/kg of body weight for 5
      days. The pancreases of obese mice had higher concentrations of insulin and PP,
      and treatment with exogenous bPP increased endogenous PP in the pancreases of
      both phenotypes. Treatment with exogenous bPP also increased the insulin content
      of obese pancreases, but was without effect in pancreases of lean mice.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1994380
TI  - Abnormal B-cell function in rats with non-insulin-dependent diabetes induced by
      neonatal streptozotocin: effect of in vivo insulin, phlorizin, or vanadate
      treatments.
AB  - Neonatal rats treated with streptozotocin on day 5 after birth (n5-STZ model)
      exhibited, when fully grown, a frank basal hyperglycemia (17.4 +/- 0.7 vs. 6.6 +/
      0.2 mmol/L in nondiabetic rats), a specific failure of glucose-induced insulin
      release, and hyperresponse to arginine. To investigate whether or not chronic
      correction of the hyperglycemia can improve the defects on insulin secretion, we
      tested diverse maneuvers, all of which aimed to lower chronically the
      hyperglycemia. Insulin secretion was studied with the isolated perfused pancreas
      preparation. A 16-day subcutaneous insulin therapy (approximately 10 U/kg/day)
      unevenly correcting the plasma glucose levels (10.8 +/- 1.6 mmol/L) did not
      improve the lack of insulin response to glucose while the arginine-induced
      insulin release returned to values close to normal. A 28-day intraperitoneal
      phlorizin infusion (50 mg/kg/day0 or a 20-day oral vanadate administration (40
      mg/kg/day) caused near normalization of the basal plasma glucose level in the
      treated n5-STZ rats (7.8 +/- 0.5 and 8.2 +/- 0.5 mmol/L, respectively).
      Nevertheless, these treatments did not correct the insulin secretion in response
      to glucose nor the hyperresponsiveness to arginine. Furthermore, we investigated
      whether or not glucopenia in vitro could restore the glucose-induced insulin
      release in this diabetic model. After a 50 min glucose-free period, the insulin
      response to a subsequent glucose stimulation still did not materialize. These
      observations suggest that in the present n5-STZ diabetic model, (a)
      hyperresponsiveness to arginine cannot be solely regarded as a residual effect of
      hyperglycemia; (b) the return to normal values of insulin release in response to
      arginine after insulin therapy, despite a still prevailing mild hyperglycemia,
      suggests that exogenous insulin per se may regulate to some extent the diabetic B
      cells; and (c) near normalization of the basal glucose levels is not a sufficient
      condition to obtain improvement of the B-cell response to glucose, such a finding
      being consistent with the concept that stringent normalization of glycemia is a
      prerequisite.

PMID- 1994382
TI  - Binding sites for the cytotoxic metabolites of estramustine phosphate (Estracyt)
      in rat and human pancreas that are distinct from pancreatic estrogen-binding
      protein.
AB  - The interaction of estramustine and estromustine, cytotoxic metabolites of
      estramustine phosphate (Estracyt), with protein-binding sites in rat pancreatic
      tissue was examined. These compounds were bound with relatively high affinity (Kd
      10 nmol/L) to binding sites constituting 0.02-0.03% of total protein. Further
      characterization of these binding sites revealed a native molecular weight of 24
      30,000 a sedimentation coefficient of 3.4 S, and a heterogenous surface-charge
      distribution by ion-exchange chromatography. Removal of endogenously bound
      ligand(s) by acetone precipitation or charcoal treatment increased binding
      significantly. Similar binding sites were present in two of two human pancreatic
      tumors, but was low or absent in the only histopathologically normal pancreas
      examined as well as in serum and pancreatic juice. These binding sites were
      distinct from the "estrogen-binding protein" reported in normal pancreas from
      various species, but were similar to the "estramustine-binding protein" (EMBP) in
      rat ventral prostate with respect to ligand specificity and the positive effect
      of endogenous ligand removal on binding. Furthermore, specimens demonstrating
      presence of these binding sites also indicated cross-reactivity with antibodies
      raised against the latter protein, suggesting an immunochemical relation between
      estra-/estromustine-binding sites in the pancreas and rat prostate EMBP. The
      presence of high-affinity sites for estramustine and estromustine in human
      pancreatic carcinomas make this type of tumor a possible target tissue for
      compounds that exert antiproliferative as well as antimitotic activity in vitro.

PMID- 1994381
TI  - Immunochemical determination of porcine pancreatic colipase: differentiation
      between procolipase and its trypsin-activated form.
AB  - A noncompetitive enzyme-linked immunosorbent assay (ELISA) has been developed for
      the quantitative determination of porcine pancreatic colipase. Calibration curves
      were established by coating polystyrene immunoplates with pure procolipase or its
      trypsin-activated derivative. Bound antigen was detected with antiporcine
      procolipase polyclonal antibodies. Under optimizing conditions, the minimal
      detectable amount of porcine colipase was 0.1 ng, which is about 1,000 times less
      than the minimal amount that can be assayed titrimetrically. The useful range of
      the immunoassay was between 0.1 to 1 ng (2-20 micrograms/L). Under standard assay
      conditions, no distinction can be made between the precursor and activated forms
      of the cofactor. Results of immunochemical determinations of colipase in porcine
      pancreatic juice and tissue extract were in good agreement with those obtained
      with the potentiometric method. The specific determination of activated colipase
      in pancreatic juice was performed by coating the immunoplates with antigen in
      solution in PBS with 0.5 g/L of Tween 20. The detergent selectively impaired the
      binding of procolipase to the plate. Determination of colipase in human
      pancreatic juice carried out under the same experimental conditions showed that
      the minimal amount of human cofactor detectable with ELISA was 1 ng due to
      partial immunological crossreactivity of the human and porcine proteins.
      Immunoassay performed with antiporcine procolipase monoclonal antibodies (Mab)
      showed lower sensitivity than that performed with polyclonal antibodies. However,
      Mab 72.11, a monoclonal antibody that reacted only with porcine procolipase,
      allowed specific detection and differential determination of the precursor form
      of porcine colipase in pancreatic juice. ELISA performed with pure human colipase
      indicated that no antiporcine procolipase monoclonal antibodies cross-reacted
      with the human cofactor.

PMID- 1994383
TI  - The effect of pancreatic polypeptide and peptide YY on pancreatic blood flow and
      pancreatic exocrine secretion in the anesthetized dog.
AB  - Pancreatic polypeptide (PP) and peptide YY (PYY) are inhibitors of pancreatic
      exocrine secretion in vivo but not in vitro, which suggests intermediate
      mechanisms of action. To examine the role of pancreatic blood flow in these
      inhibitory effects, xenon-133 gas clearance was used to measure pancreatic blood
      flow while simultaneously measuring pancreatic exocrine secretion. PP or PYY (400
      pmol/kg/h) was administered during the intermediate hour of a 3-h secretin (125
      ng/kg/h)/cholecystokinin octapeptide (CCK-8) (50 ng/kg/h) infusion. Exocrine
      secretion and pancreatic blood flow during the PP or PYY hours were compared with
      that observed in the first and third hours of the secretin/CCK-8 infusion. PP and
      PYY significantly inhibited secretin/CCK-8-induced pancreatic exocrine secretion.
      In addition, PYY (but not PP) significantly reduced pancreatic blood flow during
      secretin/CCK-8 stimulation. Nevertheless, there was no correlation between
      pancreatic blood flow and bicarbonate or protein outputs. It is concluded that
      changes in pancreatic blood flow do not mediate the inhibitory effects of PP or
      PYY on the exocrine pancreas.

PMID- 1994384
TI  - Relationship between DNA ploidy and survival in patients with exocrine pancreatic
      cancer.
AB  - The DNA ploidy of pancreatic cancer tissue from paraffin blocks was measured by
      flow cytometry in 46 patients whose disease had been detected and treated with
      surgery. Lymph node involvement was observed at the time of diagnosis in 36% of
      patients with diploid tumors and in 79% of patients with aneuploid tumors (p =
      0.017), but no clear relation to metastasis could be observed (p = 0.201). The S
      phase fraction (SPF) was significantly higher in aneuploid than in diploid tumors
      (p = 0.007). All patients who underwent radical surgery had diploid DNA content
      and SPF below the median (11.5%). Seven patients with a diploid tumor (32%) and
      none of the aneuploid cases survived 1 year. Over the 1-year period, in order of
      importance, the type of treatment (p less than 0.001), DNA ploidy (p = 0.004),
      tumor size (p = 0.0046), and lymph node status (p = 0.027) predicted survival.
      Aneuploidy showed a significant association with decreased cumulative survival (p
      = 0.015), and a suggestive relationship with SPF was found. The results suggest
      that DNA ploidy of pancreatic cancer can be used in dividing the patients into
      different prognostic groups. The value of the detection of aneuploidy, however,
      is limited, because diploid pancreatic cancers are also generally rapidly fatal.

PMID- 1994385
TI  - Regulation of rat pancreatic nuclear triiodothyronine receptor by glucocorticoid.
AB  - The nuclear T3 receptors in rat pancreas exhibit a characteristic maturation
      pattern during development and are subjected to autologous regulation by thyroid
      hormones. To see if glucocorticoids also regulate T3 receptors in the pancreas,
      rats at various age groups were subjected to experimental conditions that altered
      their glucocorticoid status and the corresponding changes in nuclear T3
      receptors, and exocrine enzymes in their pancreata were evaluated. Hydrocortisone
      administration to normal suckling and weaning rats did not change total T3
      binding capacity or the dissociation constant as measured at 30 degrees C (Kd30).
      A significant increase in the degree of occupancy of the T3 receptor was found at
      5-10 days after treatment with hydrocortisone (42.2 + 4.1% vs. 19.2 + 2.0%). T3
      binding capacity and exocrine enzyme concentrations were significantly reduced in
      both adrenalectomized (Adx) pups and adults, indicating a continuous dependency
      on glucocorticoid from preweaning to adulthood. In adrenalectomized rat pups,
      either T4 or glucocorticoid replacement alone restored T3 binding capacity and
      exocrine enzyme concentrations. T4 and glucocorticoid were given together to Adx
      rats, the level of stimulation of both pancreatic T3 binding capacity and
      exocrine enzyme concentrations was found to be equal to the sum of the
      stimulation by each of these hormones when given alone. Furthermore, a good
      correlation was found between Bmax30 (Bmax measured at 30 degrees C, representing
      total sites) for T3 binding and exocrine enzyme activities in different groups
      following various experimental treatments. These findings provide further
      evidence that thyroxine can act directly on the rat pancreas presumably through
      the T3 receptor in regulating the postnatal development of the exocrine enzymes.

PMID- 1994386
TI  - Lower-extremity arteriography: current approach and techniques.

PMID- 1994387
TI  - Absorbed dose in imaging: why measure it?

PMID- 1994388
TI  - Comments on interventional neuroradiology.

PMID- 1994389
TI  - Intracranial aneurysms: interventional neurovascular treatment with detachable
      balloons.

PMID- 1994390
TI  - Postcatheterization femoral artery injuries: is there a role for nonsurgical
      treatment?

PMID- 1994391
TI  - Diagnosis with CT at an electronic workstation.

PMID- 1994392
TI  - Use of CT for predicting gallstone composition: a dissenting view.

PMID- 1994393
TI  - Role of CT in characterizing gallstones: an unsettled issue.

PMID- 1994394
TI  - Assassins and zealots: variations in peer review. Special report.

PMID- 1994395
TI  - Exposure rates in high-level-control fluoroscopy for image enhancement.
AB  - High-level fluoroscopic boost options that exceed conventional exposure limits
      are available as a means of reducing quantum mottle during angiography. Federal
      law does not specify exposure limits for such high-level controls but requires
      specific means of activation to safeguard against inadvertent use. The American
      Association of Physicists in Medicine recently recommended that high-level
      exposure rates not exceed 2.58 mC/kg/min (10R/min). At six institution surveyed,
      maximum exposure rates ranged from 5.42 to 24 mC/kg/min (21-93 R/min). Activation
      of high-level capability varied from a simple foot switch to a keyed interlock
      requiring a second operator to engage. There appears to be no industry coherence
      in high-level control exposure limits as yet, although the Center for Devices and
      Radiological Health recently initiated an investigatory program.

PMID- 1994396
TI  - Dose reduction during fluoroscopic placement of feeding tubes.
AB  - By both increasing the optical iris of the video camera and removing the grid in
      fluoroscopic procedures involved in placement of a Dubbhoff feeding tube, the
      radiation dose to patients and staff was reduced by five to seven times. An
      average expected dose to a patient of about 300 mGy per procedure was reduced by
      two to three times when the grid was removed and by an additional three times
      when an iris of increased diameter was used. Because Dobbhoff procedures do not
      involve obtaining a diagnosis, the image degradation was acceptable and did not
      affect the total exposure times or ability to conduct the procedure. With the
      grid out, the difference between the mean exposure times of 5.1 minutes in 96
      patient studies done with a normal iris opening and 4.0 minutes in 52 studies
      done with an enlarged iris was not statistically significant. The importance of
      reducing patient dose is reinforced by the finding that one-third of the patients
      underwent repeated procedures, accounting for almost 60% of the total.

PMID- 1994397
TI  - Tissue doses in the upper gastrointestinal fluoroscopy examination.
AB  - A method was developed to estimate tissue doses from the upper gastrointestinal
      fluoroscopy examination. It involved measuring the technical parameters of the
      clinical examination, partitioning the dynamic examination into a set of discrete
      x-ray fields, and generating corresponding tissue does tables with an existing
      computer program. Knowledge of the radiation exposures associated with each of
      the fields enabled the calculation of tissue doses for the entire dynamic
      examination. In this limited sample (eight patients), fluoroscopy times ranged
      from 108 to 183 seconds. Radiation exposures ranged from 2.3 to 7.2 mC/kg (9.1-28
      R), thyroid doses from 0.15 to 3.5 mGy (15-350 mrad), uterine doses from 0.16 to
      1.0 mGy (16-100 mrad), lung doses from 0.90 to 4.2 mGy (90-420 mrad), and active
      bone marrow doses from 0.81 to 5.4 mGy (81-540 mrad).

PMID- 1994398
TI  - Enteroclysis and small bowel series: comparison of radiation dose and examination
      time.
AB  - Respective radiation doses and total examination and fluoroscopy times were
      compared for 50 patients; 25 underwent enteroclysis and 25 underwent small bowel
      series with (n = 17) and without (n = 8) an examination of the upper
      gastrointestinal (GI) tract. For enteroclysis, the mean skin entry radiation dose
      (12.3 rad [123 mGy]) and mean fluoroscopy time (18.4 minutes) were almost 1 1/2
      times greater than those for the small bowel series with examination of the upper
      GI tract (8.4 rad [84 mGy]; 11.4 minutes) and almost three times greater than
      those for the small bowel series without upper GI examination (4.6 rad [46 mGy];
      6.3 minutes). However, the mean total examination completion time for
      enteroclysis (31.2 minutes) was almost half that of the small bowel series
      without upper GI examination (57.5 minutes) and almost four times shorter than
      that of the small bowel series with upper GI examination (114 minutes). The
      higher radiation dose of enteroclysis should be considered along with the short
      examination time, the age and clinical condition of the patient, and the reported
      higher accuracy when deciding on the appropriate radiographic examination of the
      small bowel.

PMID- 1994399
TI  - Intracranial aneurysms: interventional neurovascular treatment with detachable
      balloons--results in 215 cases.
AB  - Patients with complex or surgically difficult intracranial aneurysms are being
      treated with interventional neurovascular techniques. With neuroleptic anesthesia
      and a transfemoral femoral approach, a silicone micro-balloon can be flow
      directed through the intracranial circulation, guided directly into the aneurysm,
      and detached. The aneurysm is thus eliminated from the circulation, and the
      parent artery is preserved. For broad-based or ectatic aneurysms, test occlusion
      followed by permanent occlusion of the aneurysm and parent vessel can be
      performed. Since 1981, 211 patients with 215 aneurysms, including 177 cases
      involving the anterior and 38 cases involving the posterior circulation, have
      been treated with this technique. In 127 cases (59.1%), the parent vessel was
      occluded; in 88 cases (40.9%), primary occlusion of the aneurysm was achieved
      with preservation of the parent artery. Therapy-related complications included 21
      deaths (9.8%) and 16 strokes (7.4%). Follow-up examinations were performed at 1,
      3, and 12 months after treatment, and follow-up ranged from 5 months to 9 years.
      In patients in whom standard surgical therapy fails or for aneurysms in
      surgically inaccessible anatomic locations, interventional techniques that make
      use of detachable balloons may be a useful therapeutic alternative.

PMID- 1994401
TI  - US-assisted aspiration thrombectomy: in vitro investigations.
AB  - The authors describe the use of a new ultrasound (US)-aspiration thrombectomy
      technique. An oscillating US probe was inserted into a thin-walled, large-bore
      aspiration catheter. Experiments tested the ability of the new device and other
      catheter combinations to remove clot material from a Petri dish, as well as from
      small and large vessel models made of silicone and glass tubes, respectively.
      Results of the experiments demonstrated that an oscillating 1.0-mm US probe
      inserted into an aspiration catheter (7-9 F in diameter) promoted clot
      fragmentation and allowed continuous aspiration of thrombi of any size. When
      compared with simple large-bore catheter aspiration and with mechanical
      fragmentation by means of a US probe within a catheter that was flushed to cool
      the probe, US-assisted aspiration thrombectomy demonstrated significantly better
      results for percutaneous transcatheter removal of fresh thrombi.

PMID- 1994400
TI  - Postangiographic femoral artery injuries: nonsurgical repair with US-guided
      compression.
AB  - Ultrasound-guided compression repair (UGCR) of catheterization-related femoral
      artery injuries was evaluated as a possible new imaging-guided interventional
      procedure. Thirty-nine femoral artery injuries (35 pseudoaneurysms, four
      arteriovenous fistulas) were detected with color Doppler flow imaging in patients
      with enlarging groin hematomas and/or groin bruits 6 hours to 14 days after
      catheterization procedures. UGCR was not performed in 10 patients due to
      spontaneous thrombosis (n = 4), infection (n = 1) or skin ischemia (n = 1),
      unsuitable anatomy (n = 3), or excessive discomfort (n = 1). The remaining 29
      patients underwent a full trial of compression therapy, and the lesion was
      eliminated in 27. Follow-up color flow scans were obtained after 24-72 hours in
      all 27 successful cases and at 1-15 months in 19; no recurrences or complications
      occurred. UGCR for acute injuries is safe and technically simple and is promising
      as a cost-effective, first-line treatment for uncomplicated catheterization
      related femoral artery injuries. UGCR is probably not appropriate for long
      standing injuries.

PMID- 1994402
TI  - Two urokinase dose regimens in native arterial and graft occlusions: initial
      results of a prospective, randomized clinical trial.
AB  - The effects of two urokinase (UK) dose regimens on lysis time, lytic success,
      primary clinical success, and frequency of complications of peripheral
      thrombolysis were compared. Seventy-two intraarterial UK infusions were performed
      by means of standard catheter-directed infusion techniques in 63 patients with
      symptomatic peripheral arterial or bypass graft occlusions. Patients were
      prospectively randomized to high-dose (250,000 U/h for 4 hours and then 125,000
      U/h) or low-dose (50,000 U/h) regimens. The mean time to complete lysis was 20.8,
      26.0, 16.5, and 18.2 hours for the high-dose artery, low-dose artery, high-dose
      graft, and low-dose graft groups, respectively (P was not significant).
      Respective mean infusion durations were 27.1, 35.4, 22.2, and 25.3 hours.
      Clinical success was achieved in 65%-85% of cases. The frequency of complications
      was equivalent between groups, except for a higher frequency of minor bleeding
      complications in the high-dose group. The two urokinase dose regimens studied
      were equally effective in enabling peripheral thrombolysis.

PMID- 1994403
TI  - Gallbladder perforation and bile leakage: percutaneous treatment.
AB  - Three patients with spontaneous gallbladder perforation and one with an
      iatrogenic bile leak causing bile peritonitis were treated successfully by means
      of percutaneous catheter drainage. Three patients had cholelithiasis as the cause
      of perforation; the fourth patient had previously undergone gallstone dissolution
      with methyl tert-butyl ether lavage and developed bile peritonitis a few hours
      after removal of the catheter. In three patients, a percutaneous cholecystostomy
      catheter provided successful decompression; in the fourth patient, drainage was
      performed with a percutaneous sump catheter in the subhepatic space adjacent to
      the gallbladder. No specific complications occurred. Follow-up was performed at
      1, 12, 22, and 59 months, respectively. To date, one of the four patients has
      undergone elective cholecystectomy (1 month after drainage). The remainder of the
      patients are asymptomatic. This preliminary experience suggests that the severe
      complication of gallbladder perforation and bile leakage may be treated, at least
      temporarily, by means of percutaneous drainage.

PMID- 1994404
TI  - Nitinol gooseneck snare for removal of foreign bodies: experimental study and
      clinical evaluation.
AB  - The authors describe their use of a new right-angle snare made of nickel-titanium
      (nitinol) cable for retrieval of foreign bodies and iatrogenically placed
      devices. The snare loop is at right angles to the cable and comes in five sizes
      (5, 10, 15, 25, and 35 mm); its radiographic visualization is enhanced by gold
      plated tungsten coils. This snare was used to retrieve wire and catheter
      fragments introduced into the thoracic vasculature of four dogs. Eleven of 13
      attempts were successful. Three attempts to retrieve intravascular foreign bodies
      were successful in two patients; in one of these patients, a 10-mm snare was used
      to remove a fractured end of a ventriculoatrial shunt tube from the left
      pulmonary artery. In three other patients, four ureteral stents were successfully
      removed under fluoroscopic guidance. All retrievals were performed through a
      vascular sheath and with standard techniques and angiographic equipment. No
      complications were seen in any of the patients or dogs.

PMID- 1994405
TI  - Peripheral arterial occlusive disease: prospective comparison of MR angiography
      and color duplex US with conventional angiography.
AB  - Conventional angiography, two-dimensional inflow magnetic resonance (MR)
      angiography, and color duplex ultrasound (US) were performed on 12 patients in a
      blinded, prospective study. The ability to grade arterial lesions and plan
      revascularization interventions were compared. Arterial lesions were categorized
      as nonsignificant (0%-49% diameter reduction) or significant (50%-100% diameter
      reduction). Determination of nonsignificant and significant lesions with MR
      angiography was in agreement with that at conventional angiography in 100 of 140
      lesions (71%). Agreement between results of conventional angiography and color
      duplex US occurred with 114 of 123 infrainguinal lesions (93%). Twenty-one
      vascular interventions were planned by using conventional angiography; there was
      agreement with color duplex US in 11 cases and MR angiography in five. Color
      duplex US performed well in the assessment of infrainguinal disease but was
      limited in the evaluation of iliac segments because of nonvisualization. The
      iliac region was visualized in more patients with MR angiography than with color
      duplex US, but image quality with MR angiography was inconsistent. Strategies to
      improve MR angiography of the peripheral vasculature merit further study.

PMID- 1994406
TI  - Quantification of vascular stenosis with color Doppler flow imaging: in vitro
      investigations.
AB  - The accuracy of quantifying the degree of vascular stenosis with color Doppler
      flow imaging (7.5-MHz, linear array system) was determined in an experimental
      study carried out on six concentric and five eccentric model stenoses (cross
      sectional area reduction, 13.4%-93.8%). The measurements were made with use of
      pulsatile flow at four different flow rates (70.8-339.0 mL/min). The degree of
      stenosis was calculated from the ratio of prestenotic to intrastenotic flow
      velocity. The most exact measurement of the degree of stenosis could be achieved
      with Doppler spectral analysis by determining the maximum peak systolic velocity
      (r = .994, y = 0.98x - 3.2). With the velocity values derived only from the color
      coded image, it was also possible to find the most exact degree of stenosis (r =
      .995, y = 0.99x - 2.9). For quantification of stenosis, pre- and intrastenotic
      Doppler spectral analysis is no longer necessary if the stenosis can be imaged
      sufficiently with color Doppler.

PMID- 1994407
TI  - Pulmonary atelectasis: signal patterns with MR imaging.
AB  - To assess the signal characteristics of different types of pulmonary atelectasis
      on magnetic resonance (MR) images, the authors studied obstructive atelectasis
      (OA) in 17 patients and nonobstructive atelectasis (NOA) in 25 patients. All
      patients underwent electrocardiographically gated MR imaging studies of the
      thorax with standard spin-echo sequences. No signal differences were observed
      between either type of atelectasis on T1-weighted images. Conversely, OA and NOA
      appeared significantly different on spin-density-weighted images (P less than
      .001) and on T2-weighted studies (P less than .0001). On T2-weighted images, all
      17 cases of OA appeared hyperintense, whereas 22 of 25 cases of NOA demonstrated
      a very low signal intensity. Differences in the pathophysiology of OA and NOA
      presumably account for this observation. In OA, alveolar air is totally resorbed
      and secretions accumulate in the obstructed lung. The resulting increase in free
      fluid prolongs the T2 relaxation times and leads to high signal intensity on T2
      weighted images. In NOA, the short T2 relaxation time of lung tissue in the
      absence of secretions and potential magnetic susceptibility effects due to
      residual air are likely to be responsible for the low T2 signal pattern.

PMID- 1994408
TI  - Fungal pulmonary infections after bone marrow transplantation: evaluation with
      radiography and CT.
AB  - The authors reviewed 55 pairs of chest radiographs and computed tomographic (CT)
      studies obtained in 33 febrile bone marrow transplant (BMT) recipients. The
      images were read separately, without knowledge of the clinical diagnosis. Twenty
      one episodes of fungal infection were documented. One chest radiograph showed a
      pneumonia-like opacity, and 17 showed nodular opacities, five with cavitation. In
      20 of 21 episodes, CT showed nodules with cavitation (n = 7), halo (n = 4), hazy
      margin (n = 5), air bronchogram (n = 2), cluster of fluffy nodules (n = 1), or
      sharp margin (n = 1). In none of the nine bacteremic episodes, however, were
      there opacities on chest radiographs or CT studies. CT studies demonstrating
      complicated nodules in febrile BMT patients strongly suggest a fungal infection,
      whereas negative CT studies suggest bacteremia or non-filamentous fungal
      infection of nonpulmonary origin. CT appears to add useful information to
      radiographic analysis during the assessment of febrile episodes in BMT patients,
      especially when invasive diagnostic procedures pose a high risk.

PMID- 1994409
TI  - Apical opacity associated with pulmonary tuberculosis: high-resolution CT
      findings.
AB  - To elucidate the nature of the apical opacity that is commonly seen in patients
      with tuberculosis--usually referred to as an "apical cap" or "apical pleural
      thickening"--18 patients with upper lobe tuberculosis were studied with high
      resolution computed tomography (HRCT). All had a homogeneous apical opacity at
      least 1 cm thick on chest radiographs. Fifteen of the 18 had a history of
      pulmonary tuberculosis of more than 5 years duration, and nine showed evidence of
      ipsilateral pleurisy. HRCT scans at the apex of the thorax in all nine patients
      scanned at this level showed that extrapleural fat with interspersed vessels
      accounted for most of the plain radiographic opacity. Scans obtained at a level
      slightly above visible aerated lung showed extrapleural fat 3-25 mm thick
      peripherally and atelectatic lung centrally. At more caudal levels, at which both
      aerated lung and "thickened pleura" were visible on plain radiographs, HRCT
      showed extrapleural fat (3-20 mm thick), thickened pleura (1-3 mm thick), and
      atelectatic lung peripherally and areas of emphysematous bullae, bronchiectasis,
      and atelectatic lung centrally.

PMID- 1994410
TI  - Interstitial lung disease: impact of postprocessing in digital storage phosphor
      imaging.
AB  - The ability to resolve the fine linear structures of interstitial lung disease is
      one measure of the limiting performance characteristics of an imaging system.
      Conventional screen-film radiography was compared with six algorithms of isodose
      storage phosphor digital radiography (0.2-mm x 10-bit pixel matrix) in the
      detection of interstitial lung abnormality documented by means of computed
      tomography in 40 patients with abnormalities and 25 healthy control subjects.
      Performance was evaluated with an analysis of variance (the Fisher paired
      comparison test; P less than .05) of the average receiver operating
      characteristic area of 2,730 observations by six readers. The moderately and the
      more markedly high-frequency edge-enhanced algorithms of storage phosphor digital
      radiographs were equivalent in performance to screen-film radiography. The
      default mode, low- and medium-frequency edge-enhanced algorithms, and gray scale
      reversed mode of storage phosphor digital radiography were inferior to screen
      film radiography. The authors conclude that high-frequency edge-enhanced
      algorithms can perform as well as screen-film radiography in the detection of
      interstitial disease.

PMID- 1994411
TI  - Primary CT diagnosis of abdominal masses in a PACS environment.
AB  - Whether the display medium--film versus cathode ray tube (CRT)--affects observer
      performance during interpretation of computed tomographic (CT) images is an
      important research issue in these times of implementation and growth of picture
      archiving and communications systems in radiology. The authors performed a
      multiobserver receiver operating characteristic (ROC) study to determine the
      performance of radiologists who read abdominal CT studies displayed on film, as
      well as on a high-resolution workstation (video monitor) that made use of three
      different display modes. A total of 166 examinations were evaluated by eight
      radiologists, who recorded their ordinal confidence ratings of the demonstration
      of presence or absence of abdominal masses. ROC analysis showed small differences
      in the confidence ratings assigned by individual readers for the detection and
      interpretation tasks. Results for the group as a whole showed no significant
      reduction or improvement in observer performance when ratings for any one of the
      workstation display modes were analyzed. The results of this study demonstrate
      that current CRT display technology is adequate for enabling the primary
      detection of abdominal masses with CT examinations.

PMID- 1994412
TI  - Peptic ulcer disease: CT evaluation.
AB  - The authors retrospectively describe the computed tomographic (CT) findings in 35
      patients with peptic ulcer disease. Three of eight patients with gastritis or
      duodenitis had bowel-wall thickening. Ten of the remaining 27 patients had CT
      evidence of ulcer perforation (n = 2) or penetration (n = 8), four cases of which
      were unsuspected clinically. Both patients with acute free perforation had
      pneumoperitoneum, and one showed free extravasation of orally administered
      contrast material. The precise site of perforation could not be established in
      either case with CT. The eight patients with ulcer penetration had CT evidence of
      bowel-wall thickening (n = 3) and inflammatory changes in adjacent soft tissues
      and organs (n = 8), including the pancreas (n = 4), liver (n = 1), and lesser
      omentum (n = 1). Ulcer craters were seen in only two. The CT findings of
      penetration can mimic other disease processes. CT was not useful in detecting
      uncomplicated peptic ulcer disease.

PMID- 1994413
TI  - Pancreatic transplantation: radiologic evaluation of vascular complications.
AB  - Transplantation of the pancreas is an increasingly common therapeutic option for
      preventing or delaying complications of type I diabetes mellitus. The authors
      studied the relative roles of various radiologic examinations in diagnosing
      vascular complications in these grafts including arterial and venous thrombosis,
      stenosis, and anastomotic leak (the most common vascular factors that necessitate
      pancreatectomy of the transplant), as defined with pathologic or arteriographic
      data. The results of 78 scintigraphic flow studies, 40 abdominal and pelvic
      computed tomographic (CT) scans, 27 sonograms, and eight color Doppler studies
      were evaluated in 52 patients who received a total of 27 cadaveric and 26 living
      donor grafts over a 12-year period. These results were correlated with the data
      from 45 gross and microscopic pathologic studies and 37 arteriograms to determine
      their relative value in enabling detection of graft thrombosis and other vascular
      complications. Scintigraphy, CT, sonography, and color Doppler were all sensitive
      in detection of generalized graft abnormalities but lacked specificity in
      defining the underlying etiologic factors.

PMID- 1994414
TI  - Diagnostic fine-needle puncture of the gallbladder with US guidance.
AB  - From February 1988 to January 1990, 118 fine-needle diagnostic punctures of the
      gallbladder (DPG) were performed under continuous ultrasound (US) guidance on
      symptomatic patients with gallstones. The first attempt at gallbladder puncture
      and aspiration was successful in every patient with use of a 22-gauge needle and
      continuous US visualization of the needle tip. The aspirated volume varied
      between 3 and 88 mL (average +/- standard deviation, 25.0 mL +/- 15.3). Biliary
      analysis revealed an elevation of the cholesterol saturation index in patients
      with cholesterol gallstones (attenuation at computed tomographic examination of
      50 HU or less) relative to that in patients with pigment stones (attenuation more
      than 50 HU) (1.3 +/- 0.2 vs 1.0 +/- 0.1, P less than .05). The nucleation time
      was prolonged in patients with pigment stones (19.3 days +/- 3.5 vs 1.8 days +/-
      0.8 for patients with cholesterol stones, P less than .001). All patients
      remained hospitalized for 24 hours after DPG and were reexamined on an outpatient
      basis at 1 and 3 months thereafter. No complications were detected during either
      short-term observation or long-term follow-up. The authors conclude that DPG is a
      safe and valuable technique in the diagnostic work-up of gallstone patients to
      establish their suitability for nonoperative treatment.

PMID- 1994415
TI  - Zollinger-Ellison syndrome: prospective assessment of abdominal US in the
      localization of gastrinomas.
AB  - The ability of abdominal ultrasound (US) to help localize gastrinomas was
      prospectively studied in 79 patients with Zollinger-Ellison syndrome. The results
      were assessed by means of laparotomy, autopsy, or percutaneous liver biopsy. For
      hepatic gastrinoma, US had a sensitivity of 63% and a specificity of 100%, with a
      positive predictive value of 100% and a negative predictive value of 89%. US was
      slightly less sensitive for detecting gastrinoma in the liver than were computed
      tomography (CT) (66%) and selective angiography (78%). For detection of
      extrahepatic gastrinoma, US had a sensitivity of 30%, a specificity of 94%, a
      positive predictive value of 100%, and a negative predictive value of 25%. US
      enabled detection of tumor in eight cases not detected with CT and in four not
      detected with angiography. Specificity for extrahepatic gastrinoma was similar
      for all three modalities (89%-95%). CT and US were equally effective for the
      detection of extrahepatic gastrinoma, and angiography was significantly more
      effective than both US and CT (P less than .01). The authors conclude that US,
      although of low sensitivity, remains useful as the initial imaging modality in
      patients with Zollinger-Ellison syndrome.

PMID- 1994416
TI  - Asialoglycoprotein receptor function in benign liver disease: evaluation with MR
      imaging.
AB  - An arabinogalactan-coated ultrasmall superparamagnetic iron oxide (AG-USPIO)
      preparation specific for asialoglycoprotein (ASG) receptors on hepatocytes was
      used as a magnetic resonance (MR) imaging contrast agent in the evaluation of a
      spectrum of benign liver diseases in animal models. The activity of hepatocyte
      ASG receptors, which directly reflects liver function, was directly assessed by
      measuring liver relaxation times in vitro and MR signal intensity in vivo. The
      following measurements allowed three-dimensional assessment of liver function:
      (a) liver relaxation time, (b) native MR signal intensities of liver, (c)
      response of liver to the AG-USPIO probe (percentage decrease of liver signal
      intensity after intravenous administration of 10 mumol/kg of AG-USPIO: normal
      liver 55%, fatty liver 57%, acute hepatitis 36%, chronic hepatitis 29%, and
      cirrhosis 46%), and (d) redistribution of hepatocyte-specific AG-USPIO to the
      spleen (present in hepatitis and cirrhosis but not in normal liver and fatty
      liver). The results of this study indicate that cellular hepatic abnormalities
      can be detected and quantitated with MR receptor imaging.

PMID- 1994417
TI  - Oral magnetic particles in MR imaging of the abdomen and pelvis.
AB  - Two phase 2 clinical trials of an oral superparamagnetic contrast agent for
      enhancement on magnetic resonance images of the intestine were performed. In
      trial 1, 31 male patients with cancer of the testis underwent follow-up
      examinations of the abdomen at 0.5 and 1.5 T after oral administration of
      magnetic particles. In trial 2, 31 female patients with pelvic and lower
      abdominal disease were examined at 1.5 T after administration of the contrast
      material. The patients each ingested 800 mL of contrast material over
      approximately 2 hours. Concentrations of 0.25 and 0.5 g/L did not induce blurring
      or metallic artifacts. Distribution was homogeneous through the gastrointestinal
      tract. In all patients, a loss of signal intensity was observed on proton density
      , T1-, and T2-weighted images. The diagnostic information from postcontrast
      images in trial 2 was greater in 16 patients (52%). Contrast enhancement was
      independent of field strength; no major side effects were observed. Artifacts
      from moving bowels were less troublesome, and delineation of intraabdominal and
      pelvic organs was better with the use of oral magnetic particles.

PMID- 1994418
TI  - Percutaneous rotational contact biliary lithotripsy: initial clinical results
      with the Kensey Nash lithotrite.
AB  - The percutaneous rotary lithotrite introduces a new concept to fragmentation and
      percutaneous removal of gallstones. A fluid vortex is generated, pulling calculi
      into a high-speed blade that fragments stones to predominantly under 500 microns.
      The results of treating the first 10 patients with this instrument reveal that
      large stone burdens as well as small stones (2-3 mm) of any composition can be
      removed if the gallbladder is of sufficient size to accommodate the six-pronged
      basket. Rotation times of 7-39 minutes were required. Nine of 10 procedures were
      completed; access was lost in one case. One major complication occurred. At
      repeat oral cholecystography, the gallbladder was visualized after 3-6 weeks in
      eight of the nine patients. Ursodeoxycholic acid was administered from 3 to 12
      months to five patients with either residual stones or aggregates. The hospital
      stay ranged from 48 to 72 hours. All patients (except the patient who underwent
      surgery) resumed light activity in 3-4 days and strenuous activity and full diet
      within 3 weeks.

PMID- 1994419
TI  - Epidemiologic critique of the report on adverse reactions to ionic and nonionic
      media by the Japanese Committee on the Safety of Contrast Media.
AB  - The author takes a critical look at the findings of the Katayama study of adverse
      reactions to ionic and nonionic contrast media. The author suggests that although
      the relative risks appear to be large and favor the use of nonionic media,
      serious adverse reactions were infrequent with both media types and risks were
      small on an absolute scale. In addition, the study demonstrates the potential for
      several serious information and selection biases. The accuracy of risk estimates
      are therefore called into question. Nevertheless, this study is extremely
      important in clarifying the risks associated with ionic and nonionic media during
      venography.

PMID- 1994420
TI  - Capsular transgression of prostatic carcinoma: evaluation with transrectal US
      with pathologic correlation.
AB  - One hundred twenty-five patients with biopsy proved clinical stage A or B
      prostatic carcinoma were evaluated with biplane transrectal ultrasonography (US)
      prior to radical prostatectomy. Sonograms were evaluated for capsular
      transgression of the tumor into the posterior and posterolateral aspects of the
      glands as manifested by local contour deformity and irregularity or interruption
      of the periprostatic fat echoes. Correlation of the findings at US with the
      findings at pathologic examination of the step sections was obtained, and the
      presence and depth of capsular penetration were assessed. Of the 250 halves or
      hemispheres of the prostate gland that were evaluated, capsular penetration was
      seen at pathologic examination in 86. US enabled correct identification of
      pericapsular tumor spread in 59 of the 86 hemispheres but did not depict
      pericapsular tumor spread in 27 hemispheres. Absence of pericapsular tumor spread
      was verified at pathologic examination in 149 of the 164 hemispheres that either
      did not have tumor or did not show pericapsular tumor spread. Pericapsular tumor
      spread was incorrectly diagnosed in 15 hemispheres. A positive US diagnosis of
      pericapsular tumor spread correlated moderately well with the depth of
      penetration demonstrated at pathologic examination. Transrectal US is an
      effective noninvasive procedure that demonstrates the presence of prostatic
      cancer.

PMID- 1994421
TI  - Prostate cancer: local staging with endorectal surface coil MR imaging.
AB  - Endorectal surface coil magnetic resonance (MR) imaging was used to stage the
      local extent of prostate cancer in 22 patients. The endorectal coil images were
      acquired with a 10-12-cm field of view and a 4-mm section thickness. All
      pathologic specimens were reviewed by one pathologist. Endorectal surface coil MR
      imaging was 82% accurate in the differentiation of stage B from stage C cancer.
      One case was overestimated, and three cases were underestimated. The three
      underestimated cases consisted of two cases of microscopic capsular invasion and
      one case of minimal seminal vesicle invasion. In a comparison of retrospective,
      blinded readings of endorectal coil and body coil images, there was an average
      improvement in accuracy of 16% in staging prostate cancer with endorectal coil
      images.

PMID- 1994422
TI  - Combined gadolinium-enhanced and fat-saturation MR imaging of renal masses.
AB  - Combined gadopentetate dimeglumine enhancement and fat-saturation (FS) spin-echo
      (SE) magnetic resonance (MR) imaging for the detection and characterization of
      renal masses was evaluated in 43 patients with a total of 71 lesions (28 solid
      masses and 43 cysts). SE MR sequences compared were the following: short
      repetition time (TR)/echo time (TE), conventional SE, short TR/TE FS SE, long
      TR/TE conventional SE, gadolinium-enhanced short TR/TE conventional SE, and
      gadolinium-enhanced short TR/TE FS SE techniques. MR findings were compared with
      findings of contrast-enhanced computed tomography (CT) and with pathologic
      findings in all patients. The sensitivities for detection of renal masses with
      gadolinium-enhanced FS (71 of 71 lesions) and with gadolinium-enhanced short
      TR/TE conventional (65 of 71 lesions) SE sequences were significantly (P less
      than .01) greater than with any unenhanced (short TR/TE conventional [40 of 71
      lesions], or long TR/TE [39 of 71 lesions]) SE sequence. Lesion characterization
      was also best with the gadolinium-enhanced FS SE sequence (65 of 71 lesions
      correctly classified). When combined pre- and postcontrast short TR/TE FS SE
      images were analyzed with both qualitative (visual) and quantitative (region-of
      interest measurements) assessment, lesion characterization improved even further
      (70 of 71 lesions were correctly characterized). All lesions detected with CT
      were visualized with the gadolinium-enhanced FS SE MR sequence, which in addition
      depicted seven cysts and two small renal cell carcinomas. In summary, the use of
      gadopentetate dimeglumine, especially when combined with the FS technique, was
      superior to unenhanced MR imaging for detection and characterization of renal
      lesions.

PMID- 1994423
TI  - Epithelial tumors of the ovary: CT findings and correlation with US.
AB  - One hundred thirty patients with 170 epithelial ovarian tumors were prospectively
      studied with computed tomography (CT) before surgery. Ultrasound (US) was
      performed in 108 patients with 138 tumors. At pathologic examination, 78 tumors
      (46%) were benign, 14 (8%) borderline, and 78 (46%) malignant. CT results were
      compared with surgical and pathologic findings in all patients. CT enabled
      detection of 148 of 170 tumors (87%), and US enabled detection of 118 of 138
      tumors (86%). Benign serous cystadenomas (n = 42) were correctly characterized
      with a sensitivity of 69% at CT and 70% at US. Benign mucinous cystadenomas (n =
      21) were correctly characterized with a sensitivity of 62% at CT and 50% at US.
      Malignancy was suggested in nine of 14 patients (64%) with borderline tumors at
      CT and in five of 14 (36%) at US. The overall accuracy of characterization of
      benign versus malignant tumors (including borderline tumors) was 94% with CT and
      80% with US. In the 108 patients studied with both CT and US, the sensitivity of
      CT was significantly superior to that of US (P less than .03), whereas there was
      no significant difference in specificity (P = .125).

PMID- 1994424
TI  - Renal vein renins: inability to predict response to revascularization in patients
      with hypertension.
AB  - To determine whether the captopril-stimulated renal vein renin ratio (CSRVRR)
      could enable identification of patients with hemodynamically significant
      renovascular lesions who would respond to revascularization, the authors measured
      CSRVRRs in 143 consecutive patients with hypertension who had been selected
      because of clinical features suggestive of renovascular hypertension. All
      patients underwent conventional renal arteriography. Renovascular hypertension
      was the final diagnosis if revascularization resulted in cure or improvement in
      blood pressure. Complete data were available for 133 patients. Twenty patients
      had renovascular hypertension; CSRVRR was greater than 1.5 in 13 of these 20
      patients (sensitivity, 65%). However, it was also greater than 1.5 in 54 of the
      113 patients without renovascular hypertension (false-positive rate, 47.8%). The
      positive predictive value of CSRVRR was 18.6%; the negative predictive value,
      89.3%. It is concluded that CSRVRR is not sufficiently sensitive to enable
      prediction of which patients will respond to revascularization and is not
      specific enough to exclude patients who do not have renovascular hypertension.

PMID- 1994425
TI  - Extrauterine findings of ectopic pregnancy of transvaginal US: importance of
      echogenic fluid.
AB  - Transvaginal ultrasound (US) studies of 232 consecutive patients with positive
      serum pregnancy tests who were considered to be at risk for ectopic pregnancy
      were prospectively evaluated to determine the significance of various
      extrauterine findings, including echogenic fluid in the cul-de-sac. All patients
      were found to have a surgically proved ectopic gestation (group 1, 68 patients
      [29.3%]), reliable evidence of intrauterine pregnancy at initial transvaginal US
      (group 2, 83 patients [35.8%]), or no evidence of pregnancy at initial
      transvaginal US, but subsequent proof of an intrauterine pregnancy (group 3, 81
      patients [34.9%]). Adnexal findings were demonstrated in 45 (66%) group 1
      patients, including a living extrauterine embryo in 10 (15%), an extrauterine
      gestational sac in 21 (31%), and an adnexal mass in 14 (21%). Intraperitoneal
      fluid was detected in 43 (63%) group 1 patients and in 81 (31%) group 3 patients.
      Echogenic fluid was the only abnormal finding at US in 10 (15%) group 1 patients
      and added confidence to the diagnosis of ectopic pregnancy in many others.
      Echogenic fluid correlated with hemoperitoneum at the time of surgery. The
      presence of echogenic fluid indicates a high risk for ectopic pregnancy in women
      referred with this clinical indication.

PMID- 1994426
TI  - Antropyloric muscle thickness at US in infants: what is normal?
AB  - The authors reviewed the ultrasonographic (US) images and medical records of 145
      consecutive infants who were seen for evaluation of the upper gastrointestinal
      tract because of chronic vomiting and/or regurgitation. At US, the antropyloric
      muscle of each patient was measured in the midlongitudinal plane. On the basis of
      this measurement, the patients were divided into the following categories: group
      1 (1-2 mm; 99 patients), group 2 (greater than or equal to 3 mm; 40 patients),
      and group 3 (2- less than 3 mm; six patients). Patients in group 1 were
      considered to have normal antropyloric muscle thickness, those in group 2 had
      abnormal thickness, and those in group 3 had muscle thickness that was not
      definitely normal or abnormal. The final clinical diagnoses for all of the
      infants in the three groups confirmed the authors' initial impressions that
      antropyloric muscle thickness of less than 2 mm was anatomically normal, muscle
      measuring 3 mm or greater was abnormal and diagnostic for pyloric stenosis, and
      muscle from 2 to less than 3 mm was abnormal but not specifically diagnostic for
      pyloric stenosis. Two of the six patients in group 3 eventually were diagnosed as
      having pyloric stenosis; thus, the authors believe that only those patients with
      antropyloric muscle less than 2 mm thick should be considered unequivocably
      normal.

PMID- 1994428
TI  - Lumbar spinal nerves in the neural foramen: MR appearance.
AB  - The appearance of the proximal lumbar spinal nerves at magnetic resonance (MR)
      imaging has not, to the authors' knowledge, been described. MR images and exactly
      corresponding sections obtained from four cadavers by means of a freezing
      microtome were correlated to characterize the MR appearance of the proximal
      spinal nerves. The junction of the dorsal and ventral rami with the dorsal and
      ventral roots consists of a group of six to 15 fascicles measuring 2-6 mm in
      length. These fascicles appear in MR images obtained with short repetition times
      as small foci of lower signal intensity than that of surrounding fat. The
      proximal spinal nerve and its relationship to the intervertebral disk and osseous
      margins of the neural foramen can be demonstrated effectively with MR imaging.

PMID- 1994427
TI  - Lesions that manifest as medial cheek and nasolabial fold masses.
AB  - Seventeen cases were collected in which the patient presented with a medial cheek
      or nasolabial fold mass. Most of these lesions were uncommon, and some were rare.
      The most reliable differentiating finding was the type of associated bone
      involvement. The malignancies had bone erosion and as a group could be
      distinguished from the other masses. Computed tomographic attenuation and
      magnetic resonance imaging signal intensities were nonspecific and did not allow
      a definitive diagnosis to be made. The types of pathologic conditions and their
      sectional imaging findings are reviewed.

PMID- 1994429
TI  - Nerve root avulsion of birth palsy: comparison of myelography with CT myelography
      and somatosensory evoked potential.
AB  - Findings at myelography and computed tomographic (CT) myelography were reviewed
      in 21 patients (22 limbs) with birth palsy; nerve root shadows were the focus of
      this study. Myelography demonstrated 51 completely avulsed roots (78%) and 14
      incompletely avulsed roots (22%). A traumatic meningocele was detected at 38
      roots on myelograms and 51 roots on CT myelograms. Thirteen avulsed roots (eight
      completely and five incompletely avulsed roots) (20%) were not associated with a
      meningocele. In nine patients who underwent brachial plexus exploration,
      myelographic findings were compared with root somatosensory evoked potential
      (SEP). SEP was not induced at 22 of 25 completely avulsed roots and was induced
      at all seven incompletely avulsed roots. Myelography and SEP were consistent in
      29 of 32 roots (91%). It is concluded that myelography is indispensable for
      preoperative evaluation of cervical nerve root avulsion of birth palsy, because
      CT myelography is not sensitive to nerve root avulsion without a traumatic
      meningocele, and SEP cannot enable one to discriminate incomplete avulsion from
      intact roots.

PMID- 1994430
TI  - Mapping the distribution of amobarbital sodium in the intracarotid Wada test by
      use of Tc-99m HMPAO with SPECT.
AB  - The intracarotid amobarbital sodium, or Wada, test has been used to localize
      speech and memory function prior to surgical treatment of temporal lobe seizures.
      The authors mixed technetium-99m hexamethyl-propyleneamine oxime (HMPAO) with
      amobarbital sodium and injected the mixture in 25 patients with epilepsy. Single
      photon emission computed tomography (SPECT) of the brain was then performed to
      determine intracerebral distribution of the amobarbital sodium. Results of SPECT
      were compared with those of conventional and digital subtraction angiography
      (DSA). The distribution of Tc-99m HMPAO and, presumably, amobarbital sodium
      varied from patient to patient. SPECT revealed a statistically different
      distribution from that predicted with conventional angiography. The distribution
      also often differed from that of DSA, although the difference was not
      significant. SPECT revealed infrequent delivery to mesial temporal lobe
      structures. This emphasizes the need for caution in the use of the intracarotid
      amobarbital sodium test to predict the outcome of removal of these areas.

PMID- 1994431
TI  - Osteonecrosis of the knee after arthroscopic surgery: diagnosis with MR imaging.
AB  - Spontaneous osteonecrosis about the knee typically is a disease of the elderly
      characterized by an acute onset of pain. The exact cause of this condition has
      long been debated, although a causative relationship between meniscal tears and
      spontaneous osteonecrosis about the knee has been postulated. Seven patients with
      knee pain, meniscal tears, and chondromalacia without initial evidence of
      osteonecrosis at magnetic resonance (MR) imaging underwent arthroscopic surgery
      with meniscal recontouring or repair and cartilage shaving. These patients
      returned within 2-14 months with recurrent pain in the treated knee. MR imaging
      then demonstrated abnormalities consistent with osteonecrosis. Osteonecrosis of
      the femoral condyle or tibial plateau may be a late sequela of meniscal injury in
      association with chondromalacia and arthroscopic surgery. This diagnosis should
      be suspected in patients with recurrent knee pain after arthroscopic repair of
      meniscal tears. The precise relationship of this pattern of osteonecrosis to that
      previously described as spontaneous requires further investigation.

PMID- 1994432
TI  - Tibial collateral ligament bursa: MR imaging.
AB  - The bursa of the tibial collateral ligament (TCL) may be visualized at magnetic
      resonance (MR) imaging when it becomes distended with fluid. In the authors'
      experience, this finding signifies a pathologic condition either in the medial
      capsuloligamentous complex or in the bursa itself. Such a finding may indicate
      TCL bursitis. TCL bursitis can be suspected in the setting of isolated pain in
      the medial joint line in the absence of mechanical symptoms. Prolonged relief of
      symptoms after injection of steroid into the bursa is supportive of the
      diagnosis. Seven cases are presented in which a fluid-filled TCL bursa was
      identified at MR imaging. In five cases, TCL bursitis was suspected. The
      differential diagnosis for the MR findings is discussed.

PMID- 1994433
TI  - Tears of cruciate ligaments and menisci: evaluation with cine MR imaging.
AB  - A cine magnetic resonance (MR) imaging technique, involving the acquisition of
      kinematic sagittal images during knee movement, was used to evaluate 52
      symptomatic knee joints. Results were compared with those obtained by means of
      static three-dimensional (3D) MR imaging. Twenty-seven of the 28 anterior
      cruciate ligament (ACL) tears and 22 of 24 normal ligaments were correctly
      identified at cine MR imaging for a sensitivity of 96% and a specificity of 92%.
      Static 3D MR imaging yielded a sensitivity of 71% and a specificity of 88%. All
      four posterior cruciate ligament tears were identified at cine and 3D MR imaging.
      For meniscal tears, cine MR imaging yielded a sensitivity of 48% and a
      specificity of 96%; the sensitivity and specificity for 3D MR imaging were 71%
      and 96%, respectively. Cine MR imaging proved to be more useful than static MR
      imaging in assessing the tightness of cruciate ligaments, especially of those
      that were partially torn, and in assessing the movement of meniscal-free
      fragments. The increased information obtained with cine MR imaging may warrant
      continued investigation and clinical application.

PMID- 1994434
TI  - Mycetoma: comparison of MR imaging with CT.
AB  - Magnetic resonance (MR) images obtained in 18 patients with pathologically
      confirmed mycetoma in the body (n = 4) or lower extremity (n = 14) were
      retrospectively reviewed and compared with computed tomographic (CT) scans in 15
      patients and surgical findings in 10. T1-weighted images showed an infiltrating
      mass (same signal intensity as muscle) involving skin, subcutaneous fat, muscles,
      tendons, and other tissues. On T2-weighted images, the mass and affected
      structures showed moderately increased signal intensity. Bone marrow involvement
      was detected in seven patients and was best visualized on T1-weighted images. CT
      showed moderate enhancement of the infiltrative process in all patients. Bone
      changes, seen in nine, included coarse trabeculation, periosteal reaction,
      endosteal proliferation, and patchy destruction. MR imaging and CT were
      comparable and correlated well with surgery in showing the extent of soft-tissue
      involvement. Early bone changes (important for therapy planning for pedal
      mycetoma) were seen only at CT. The study showed that MR imaging is sensitive for
      assessing the extent of mycetoma in the soft tissues. CT should be the method of
      choice for staging pedal lesions because it can be used to detect early bone
      involvement.

PMID- 1994435
TI  - Deposition of calcium pyrophosphate dihydrate crystals in the ligamentum flavum:
      evaluation with MR imaging and CT.
AB  - Four patients had spinal canal stenosis associated with deposition of calcium
      pyrophosphate dihydrate within the ligamentum flavum. Radiologic evaluation was
      performed with magnetic resonance imaging or computed tomography, and surgery was
      performed on all four patients. Pathologic examination of the surgical specimens
      demonstrated deposits of calcium pyrophosphate crystals within the ligamentum
      flavum. Focal enlargement of the ligamentum flavum was present in the cervical
      spine (n = 1), while a more diffuse, bilateral enlargement was identified in the
      lumbar spine (n = 3). Enlargement of the ligament either caused or was a
      component of spinal stenosis that caused neurologic signs or symptoms. Three of
      the patients had evidence of calcium pyrophosphate deposition elsewhere.
      Deposition of calcium pyrophosphate dihydrate within the ligamentum flavum
      causing either focal or diffuse enlargement can be associated with significant
      spinal stenosis.

PMID- 1994437
TI  - Simple test pattern for mammographic screen-film contact measurement.
AB  - Test patterns to measure mammographic screen-film contact require the use of a
      much finer screen-wire mesh than can be used in test patterns for other
      diagnostic cassettes. The author has found that a radiographic grid of any line
      spacing equal to or exceeding 40 lines per inch can be used to test mammographic
      screen-film contact, making it unnecessary to purchase a special dedicated fine
      mesh mammographic test pattern. However, the use of a magnification technique
      will often be required, since modern grids have mesh frequencies in excess of 100
      lines per inch.

PMID- 1994436
TI  - Intraoperative I-125 seed implantation for extensive recurrent head and neck
      carcinomas.
AB  - From 1978 to 1988, 41 patients with extensive recurrent carcinomas of the head
      and neck were treated with surgical resection plus intraoperative iodine-125 seed
      implantation. Surgery was performed to resect the tumors and to expose the tumor
      beds for implantation. I-125 seeds were implanted intraoperatively, with a
      spacing of 0.75-1 cm between adjacent seeds, either into the soft tissue in the
      tumor bed or onto small patches of gelatin sponges to cover the bone, nerve, or
      blood vessel involved with disease. Reconstructive flaps were used in 18
      patients. The average I-125 dose delivered by the implanted seeds was 8,263 cGy.
      The determinate 5-year actuarial survival rate for the entire group was 40%. The
      5-year local disease control rate was 44%. Major complications were transient
      wound infection (32%), flap necrosis (24%), fistula formation (10%), and carotid
      blowout (5%). These results indicate that surgical resection plus I-125 seed
      implantation provides a potentially curative treatment for patients with
      extensive recurrent head and neck carcinomas that would be considered
      traditionally unresectable and that would be treated only with palliative
      therapy.

PMID- 1994438
TI  - Improved fat suppression in STIR MR imaging: selecting inversion time through
      spectral display.
AB  - By observing the fat-signal peak on the spectral display of a magnetic resonance
      (MR) imager while varying inversion time (TI), the authors determined the TI that
      produced the lowest fat peak for the best suppression of fat signal in subsequent
      short-TI inversion-recovery (STIR) MR imaging. In 25 volunteers who underwent
      imaging at multiple TIs, the TI that produced the lowest measured fat signal
      intensity was the same as that selected by means of TI tuning in 60% of cases and
      was within 5 msec in the remaining 40%.

PMID- 1994439
TI  - Turf and technology.

PMID- 1994440
TI  - Interpretation of submerged laminar jets: ureteric jet phenomenon.

PMID- 1994441
TI  - Osteomyelitis: detection with US.

PMID- 1994442
TI  - Oblique sagittal MR imaging of the anterior cruciate ligament.

PMID- 1994443
TI  - Nonionic or neutral?

PMID- 1994444
TI  - Use of oximetry during MR imaging of pediatric patients.

PMID- 1994445
TI  - Cystic encephalomalacia in twin embolization syndrome.

PMID- 1994446
TI  - Increasing coauthorship of scientific exhibits.

PMID- 1994447
TI  - Neuroradiology.

PMID- 1994448
TI  - Magnetic resonance.

PMID- 1994449
TI  - Technical exhibits.

PMID- 1994450
TI  - Abdominal-gastrointestinal radiology.

PMID- 1994451
TI  - Computer applications and digital imaging.

PMID- 1994452
TI  - Musculoskeletal radiology.

PMID- 1994453
TI  - Thoracic radiology.

PMID- 1994454
TI  - Cardiovascular/interventional radiology.

PMID- 1994455
TI  - Arrhythmia suppression in postmyocardial infarction patients with special
      notation to cardiac arrhythmia suppression trial.

PMID- 1994456
TI  - Patient evaluation for cardiac transplantation.
AB  - The aim for cardiac transplantation is to improve the quality of life and the
      survival in patients with end-stage heart failure. Given the scarcity of donor
      organ availability, the expense of the transplantation process and follow-up
      care, as well as the tremendous emotional burden the process places on a patient
      and his/her family, it is essential to carefully screen potential candidates for
      their symptomatic, functional, hemodynamic, and psychosocial eligibility, and to
      rule out coexisting hemodynamic or comorbid conditions that would jeopardize
      successful transplantation and immunosuppression. Comprehensive screening of
      potential transplant candidates, which is best accomplished by a
      multidisciplinary team approach working closely with patients and their families,
      is essential to insure that maximum benefit is derived from this scarce and
      valuable resource.

PMID- 1994458
TI  - Environmental lead in Mexico.
AB  - From the data presented here, it can be concluded that environmental exposure to
      lead is a particularly severe problem in Mexico. As has been shown, there are
      very important sources of exposure to this metal: (a) for rural populations who
      manufacture and/or utilize lead-glazed pottery, (b) for urban populations who are
      exposed to high air lead concentrations due to the continued use of lead fuel
      additives, (c) for workers of several industries, mainly those of batteries and
      pigments, (d) for consumers who routinely eat canned foods such as hot peppers
      and fruit products, and (e) for the general population living in the vicinity of
      smelters, refineries and other industries that emit lead. Therefore, in Mexico
      only those native populations living in very primitive communities, far away from
      all civilized life, could be expected to be free from this exposure. At the same
      time, and despite the relatively few data available, it can be stated that the
      exposure to lead of populations in Mexico could be approaching levels that might
      be highly hazardous, in particular for the neuropsychological health of children.
      Regarding the presence of lead in the environment, despite the fact that the
      available studies are not enough, it is evident that pollution by this metal is
      widespread and that there is a serious lack of studies for most regions of the
      country, including several that might be expected to be highly polluted. At the
      same time, it is evident that the official attention paid to the problem, either
      in regulations, support of further studies, or implementation of effective
      control measures has been far from the level needed according to the available
      data. Lead in gasoline is still used at very high concentrations in all the
      country, with the exception of Mexico City and its surrounding area, while no
      studies have been carried out to determine the potential health and environmental
      impact of this practice in regions outside Mexico City. Despite the fact that the
      Torreon smelter is one of the largest in Latin America, and although it is
      located less than two km from downtown Torreon, with the predominant winds
      blowing in the direction from the smelter towards the residential and central
      areas of the city, no large scale study has been carried out on the impact of
      this source on the health of its residents.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1994457
TI  - Long-term complications of cardiac transplantation.

PMID- 1994459
TI  - Foodborne toxins of marine origin: ciguatera.
AB  - Ciguatera poisoning has long been recognized as a serious problem in the tropical
      and subtropical regions of the world. Due to international and interstate
      commerce and tourist travel the phenomenon is spreading to other parts of the
      globe. Various species of fish (surgeonfish, snapper, grouper, barracuda, jack,
      amberjack among others) have been implicated in this type of poisoning. These
      fish accumulate toxins in their flesh and viscera through the consumption of
      smaller fish that have been previously contaminated by feeding on toxic
      dinoflagellates. The most probable source of ciguatera is thought to be the
      benthic microorganism, Gambierdiscus toxicus, which produces both CTX and MTX,
      but other species of dinoflagellates such as Prorocentrum lima may also
      contribute with secondary toxins associated with the disease. Potentially
      ciguatoxic dinoflagellates have been isolated, cultured under laboratory
      conditions and dinoflagellate growth requirements as well as some factors
      affecting toxin production have been determined. Also, data from their ecological
      environment have been accumulated in an attempt to reveal a relationship with the
      epidemiology of ciguatera outbreaks. Several bioassays have been employed to
      determine the ciguatoxicity of fish. Cats have been used due to their
      sensitivity, but regurgitation has made dosage information difficult to obtain.
      Mongooses have also been used but they often carry parasitic and other type of
      diseases which complicate the bioassay. Mice have been used more commonly; they
      offer a more reliable model, can be easily housed, readily are dosed in several
      ways, and manifest diverse symptoms similar to human intoxications; but the
      amount of toxic extract needed, time consumed, complicated extraction techniques,
      and instrumentation involved limit the use of this assay commercially. Other
      bioassays have been explored including the brine shrimp, chicken, mosquito,
      crayfish nerve cord, guinea pig ileum, guinea pig atrium, and other histological
      preparations. All require elaborate time-consuming procedures, are not
      reproducible, lack specificity, and are semiquantitative at best. The techniques
      that appear to represent the major advance in identifying and detecting
      ciguatoxic fish are immunochemical methods: radioimmunoassay (RIA), competitive
      enzyme immunoassay (EIA), and enzyme-linked immunosorbent assay (ELISA). Of
      these, the enzyme immunoassay stick test is the simplest, fastest, most specific,
      more sensitive, and does not require complicated instrumentation.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 1994461
TI  - Pesticide residues in foods imported into the United States.
AB  - Interest in pesticide residues in foods has increased, and the issue of residues
      in imported foods has been raised as a potential public health problem. Three
      U.S. government agencies, EPA, FDA, and USDA, are responsible for regulating
      pesticides. EPA sets tolerances, and FDA and USDA enforce those tolerances. As
      part of its regulatory activities, FDA conducts a regulatory monitoring program
      that samples and analyzes each year approximately 20,000 food shipments, about
      60% of which are imports. Samples of imported foods are collected at ports of
      entry, and are chosen on the basis of several factors rather than on a completely
      random basis. Raw agricultural products are emphasized. Most analyses are
      performed using MRMs, to make best use of FDA's resources. Using five MRMs, about
      half of the 300 pesticides with U.S. tolerances can be determined. Results from
      monitoring over the past several years have shown that nearly 60% of the imported
      foods sampled had no pesticide residues detected. Of those samples that were
      violative, 5% contained residues for which there was no U.S. tolerance, and less
      than 1% had over-tolerance residues. Examples are given of the various
      pesticide/commodity combinations that have been found to be violative. FDA is
      often criticized for the scope of its pesticide coverage, particularly with
      regard to imported foods. Some critics have promoted the idea of a 'circle of
      poison,' which is based on the premise that pesticides banned in the U.S. are
      exported and used on foods in foreign countries; then the food containing these
      residues is imported into the U.S. and consumed. However, FDA's testing of
      imported foods has shown that residues of EPA-banned pesticides are not occurring
      from currently purposeful uses. The violation rates for imports also have not
      been significantly different from those for domestic foods. This indicates that
      foreign producers, as well as domestic growers, generally use pesticides in a
      manner consistent with EPA requirements. FDA continues to broaden its information
      gathering capabilities. As mandated by the PMIA of 1988, FDA will attempt to
      obtain pesticide use information from countries that are major food exporters to
      the United States. An improved data management system will also be in place, and
      a long-range analytical method development plan instituted. Several international
      organizations address the issue of pesticide residues in foods. Attempts at
      harmonization of national tolerances for pesticide residues have not been
      successful, i.e., a number of individual nations have not accepted Codex
      MRLs.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1994460
TI  - Toxicological-hygienic requirements for study, registration, and regulations of
      pesticides in the USSR.
AB  - This review discusses the toxicological and hygienic aspects of the extensive
      increase in pesticide use, which has resulted in the great majority of people
      throughout the world being affected by their presence. The need for a broad
      exchange at an international level of the findings of toxicological and hygienic
      research is established. Brief information on the development of pesticide
      toxicological research in the USSR is also presented. Accepted criteria for
      toxicological and hygienic pesticide assessments in the USSR are also
      systematically reviewed, with respect to the evaluation of physical and chemical
      properties, toxicity as defined through acute and subacute experiments,
      cumulative properties, and effects on skin and mucous membranes. The methodology
      for establishing threshold and noneffective (harmless) levels is also described,
      along with the prediction of delayed adverse effects. Other areas discussed
      include the classification of pesticides by degree of toxicity and danger, the
      system of research and regulation in the USSR, and the principle of integrated
      standardization of pesticide content of food, water, and atmospheric air. The
      review concludes with a look at certain prospective trends in the search for and
      development of pesticides that have selective action on target organisms but are
      harmless to human health and the environment.

PMID- 1994463
TI  - Coming back to American nursing.

PMID- 1994462
TI  - Pediatric academy's latest guidelines on Hib vaccine.

PMID- 1994464
TI  - Outpatient procedures: a little education goes a long way.

PMID- 1994465
TI  - Hypertension. Step-care management.

PMID- 1994466
TI  - How hard will it be to get your BSN?

PMID- 1994467
TI  - PTCA: treating the tough cases.

PMID- 1994468
TI  - Patient teaching for X-ray and other diagnostics. Cardiac catheterization.

PMID- 1994470
TI  - When the Dx is Crohn's disease.

PMID- 1994469
TI  - Across the OR table.

PMID- 1994471
TI  - Nursing the mind. Working with troubled teens.

PMID- 1994472
TI  - When the patient doesn't want to be resuscitated.

PMID- 1994473
TI  - A new cannibalism?

PMID- 1994474
TI  - Diet therapy helps this drug work better.

PMID- 1994475
TI  - More research needed on lymphoma in AIDS patients.

PMID- 1994477
TI  - Recent advances in intractable pain control.

PMID- 1994476
TI  - Thrombotic thrombocytic purpura--plasma infusion or exchange?

PMID- 1994478
TI  - Scorpion stings.

PMID- 1994479
TI  - 'Doomsday'--chimera or reality?

PMID- 1994480
TI  - Prevalence of biochemical and immunological abnormalities in rheumatoid
      arthritis.
AB  - The prevalence of biochemical and immunological abnormalities was studied in a
      group of 256 patients with rheumatoid arthritis (104 coloureds, 100 whites and 52
      blacks). The most common biochemical abnormalities detected were a reduction in
      the serum creatinine value (43.4%), raised globulins (39.7%), raised serum
      alkaline phosphatase level (42.3%), reduction in serum albumin value (8.1%), a
      mild rise in serum creatinine value (6.6%), and a raised serum gamma
      glutamyltranspeptidase (GGT) level (6.5%). The prevalence of a rise in the GGT
      was less frequent than reported in other published studies. The immunological
      abnormalities noted were a positive rheumatoid factor (78.9%), positive anti
      nuclear factor (36%), raised serum IgG (43.3%) and IgA (10.5%) values, positive
      smooth-muscle antibody (12.5%) and elevated double-stranded anti-DNA antibody
      levels (2.3%). Inter-group comparisons showed that the serum IgG and IgA and
      total globulins were significantly higher in blacks and coloureds than whites;
      these findings may be related to a higher prevalence of malnutrition and
      infection in childhood in these communities. There were no significant inter
      group differences that could be attributed to rheumatoid arthritis.

PMID- 1994481
TI  - The management of pulmonary tuberculosis in the border sub-region, 1983.
AB  - In order to study the management of pulmonary tuberculosis among black and
      coloured adults in the Border region of South Africa in 1983, a historical
      inception cohort representative of tuberculosis hospitals and local authority
      health services was followed up over 15 months to assess how efficiently the
      national responsibility is discharged in a region. About 75% of patients were
      sputum-positive, and 81% were judged to have had active pulmonary tuberculosis.
      The mean service delay after radiography was about 1 1/2 weeks. About 26% of
      patients were treated with a rifampicin regimen, 50% were frequent attenders and
      41% completed treatment, although about 21% were still being treated after 15
      months. There was a deficiency of laboratory information for diagnosis and
      monitoring of response to treatment. Periodic cohort evaluation and improvement
      of diagnostic efficiency, of peripheral use of laboratories, and of spending on
      community service infrastructure are essential for closing the gap between
      policies and implementation.

PMID- 1994482
TI  - Invasive v. non-invasive blood pressure measurements--the influence of the
      pressure contour.
AB  - A reasonable correlation exists between invasive and non-invasive methods of
      measuring systemic blood pressure. However, there are frequent individual
      differences between these methods and these variations have often caused the
      validity of the non-invasive measurement to be questioned. The hypothesis that
      certain invasive systolic blood pressures may represent a pressure impulse rather
      than a flow-generating pressure was used to classify the invasive pulse pressure
      contour into various types, and the invasive pressure measurement was then
      correlated with the non-invasive. There was a significantly greater difference
      between these two methods of measuring systolic blood pressure in patients
      exhibiting prominent inotropic pressure pulse phenomena compared with patients
      without such phenomena. Since non-invasive monitors measure blood pressure by
      volume displacement or flow detection and invasive ones measure pressure impulses
      rather than flow, it was concluded that the pressure measured by the non-invasive
      monitor more accurately reflects the propulsive pressure-causing flow when
      inotropic pressure pulse phenomena are present.

PMID- 1994483
TI  - Ventriculoperitoneal shunt infections in children. A 6-year study.
AB  - In a study of ventriculoperitoneal shunt infections conducted retrospectively
      between 1983 and 1987 and prospectively in 1988 39 infections from 372 shunt
      procedures (incidence 10.5%) were identified. The most common organism isolated
      was Staphylococcus aureus (18; 47%) followed by S. epidermidis (10; 26%). Forty
      two per cent of staphylococci were methicillin-resistant. Gram-negative
      infections were associated with myelomeningoceles and Gram-positive infections
      with other forms of hydrocephalus (P = 0.048). Lymphocyte predominance was found
      more frequently than polymorphonuclear predominance in cerebrospinal fluid.

PMID- 1994484
TI  - Loss of maternal measles antibody in black South African infants in the first
      year of life--implications for age of vaccination.
AB  - In order to investigate the feasibility of measles vaccination before the age of
      9 months the duration of passive immunity against measles was estimated by
      conducting a longitudinal study of measles antibody levels in 20 black neonates
      delivered at term. Measles serum antibody (IgG) was measured by enzyme-linked
      immunosorbent assay in the mother at childbirth and on consecutive samples taken
      from the infants from birth until 9 months of age. Protective measles antibody
      level was defined as greater than 200 mIU. Unprotective levels were found in 88%
      (95% confidence interval (CI) 81-99%) of 6-month-old infants, while at 9 months
      all were susceptible. The mean antibody level was 192 mIU (CI 104-348%) at 4
      months; 34 mIU (CI 15-73%) at 6 months and 13 mIU (CI 6-24%) at 9 months of age.
      Our data support the recent World Health Organisation recommendation to immunise
      children in developing countries at 6 months with the 'high titre' Edmonston
      Zagreb measles vaccine, since most infants in our study had lost passive immunity
      against measles by this age.

PMID- 1994485
TI  - Perceptions and knowledge about the acquired immunodeficiency syndrome among
      students in university residences.
AB  - Using an anonymous questionnaire to obtain baseline data on sexual behaviour and
      knowledge of the acquired immunodeficiency syndrome (AIDS) among students in
      university residences, the following information was obtained: Knowledge of AIDS
      was found to be high, although misconceptions regarding transmission of the virus
      were prevalent. Mosquito bites (15%) and the donating of blood (31%) were
      incorrectly identified as methods of transmission of the virus. Deep kissing was
      recognised by only 27% of the students as a possible method of transmission while
      22% and 13% of the students, respectively, failed to identify the sharing of
      razor blades and blood transfusions as possible means of contracting HIV
      infection. The students' knowledge had not greatly affected sexual behaviour. Two
      thirds of the respondents had previously had sexual contact; 38% were sexually
      active at the time of the study, and of these 74% had engaged in unprotected
      intercourse with casual partners in the previous 6 months. There was a negative
      attitude towards condom use and over 80% of sexually active students did not
      perceive themselves to be at risk of contracting AIDS. Campus Health (82%), State
      health services (51%), and public advertisements (60%) were preferred sources of
      AIDS information. Newspapers/magazines (80%) and leaflets (69%) were identified
      as the preferred media. In reality, significantly fewer students obtained their
      information from Campus Health (15%; P less than 0.05), State health services
      (19%, P less than 0.05) and leaflets (44%; P less than 0.05). It can be concluded
      that education programmes should be developed by credible organisations to ensure
      that an awareness of AIDS results in appropriate sexual behaviour.

PMID- 1994487
TI  - Vertically transmitted HIV-1 infection in children. A report of 23 cases.
AB  - Twenty-three children with vertically transmitted human immunodeficiency virus
      type 1 (HIV-1) infection were seen at Baragwanath Hospital between May 1989 and
      April 1990. There was a marked increase in the number of cases in 1990. Infected
      children presented at a median age of 6 months; most commonly with
      lymphadenopathy, failure to thrive and respiratory complications. Serious
      bacterial infections occurred in 39%. Reversed helper T- to suppressor T-cell
      ratios were present in all but 1 of 16 children tested and
      hypergammaglobulinaemia and anaemia (usually normocytic) were frequently present.
      Some of the children have already died and the outlook for the others is bleak.
      With the increase of HIV infection in the heterosexual population, increasing
      numbers of infected children can be expected.

PMID- 1994486
TI  - Quantifying non-compliance in patients receiving digoxin--a pharmacokinetic
      approach.
AB  - Non-compliance has a major influence on the successful outcome of a therapeutic
      regimen. It also unnecessarily increases the costs of health care. In a study
      involving 137 outpatients receiving digoxin 55 patients (40%) were found to be
      non-compliant. Patients who experienced communication problems and who lacked a
      meaningful relationship with their doctor showed a marked deterioration in
      compliance. An applied pharmacokinetic approach was used to predict the serum
      digoxin concentration for each patient. The creatinine clearance was determined
      and the degree of severity of heart failure was assessed. Total body clearance
      was then calculated. The predicted concentration was also calculated and compared
      with the measured digoxin concentration enabling an objective assessment of
      compliance. Twenty-four of the non-compliant patients who had subtherapeutic
      levels of digoxin (less than 0.8 ng/ml) had signs of cardiac failure. Eighteen of
      these patients were receiving additional medication (1.7 +/- 0.5 items) for the
      treatment of cardiac failure.

PMID- 1994488
TI  - [Lipoidproteinosis. A report of four cases].
AB  - Four cases of lipoid proteinosis (Urbach-Wiethe disease) are presented. The
      incidence, clinical features, relevant special investigations and possible
      treatment of the disease are reviewed. These patients present with hoarseness and
      lesions of the skin and mucosa. The condition is often misdiagnosed by general
      practitioners and otolaryngologists.

PMID- 1994489
TI  - Four-level spinal decompression for metastatic breast carcinoma. A case report.
AB  - A case of successful four-level anterior decompression for paraplegia due to
      metastatic breast carcinoma is reported. Posterior instrumentation carried out
      shortly afterwards provided sufficient additional stability for the patient to
      stand and walk. It is suggested that this form of aggressive management may
      provide excellent palliation in certain cases of extensive metastatic neoplastic
      disease.

PMID- 1994490
TI  - Cyclosporin A in non-dietary IgY cirrhosis.

PMID- 1994491
TI  - Anti-K (kell) antibodies in pregnancy.

PMID- 1994492
TI  - Delayed neurotoxic and cytotoxic complications after snake envenomation.

PMID- 1994493
TI  - Maternal predictors of fetal demise in trauma during pregnancy.
AB  - Trauma complicates 6 to 7 per cent of all pregnancies, but fetal demise secondary
      to maternal trauma occurs much less frequently. This study was done to analyze
      the incidence of fetal demise as a function of 21 maternal characteristics
      determined within the first 24 hours after trauma. Nine instances of fetal demise
      were identified from 73 pregnant patients with trauma admitted to four Level I
      trauma centers from a combined data base of 30,000 patients. Maternal factors
      examined by logistic regression were Injury Severity Score (ISS), Trauma Score
      (TS), Abbreviated Injury Scale (AIS), fluid requirements in the initial 24 hours,
      systolic blood pressure (SBP), heart rate (HR), hemoglobin, hematocrit and
      arterial blood gas analysis. Fetal demise was found to be associated with
      increasing ISS, increasing face and abdominal AIS, increasing fluid requirements,
      maternal acidosis and maternal hypoxia. Standard maternal laboratory and
      physiologic parameters, such as hemoglobin and hematocrit, oxygen and hemoglobin
      saturation, partial pressure of carbon dioxide, SBP and HR were not predictive.
      The TS was also found to be nonpredictive.

PMID- 1994494
TI  - The effects of calcium and calcium channel blockade on peptide YY and
      neuropeptide Y release.
AB  - The secretory response of many gastrointestinal hormones has been demonstrated to
      be mediated by way of calcium-dependent pathways. The present study was done to
      assess the effects of infusions of calcium (15 milligrams per kilogram per hour)
      and verapamil (5 milligrams per kilogram per hour) on circulatory and ileal
      intraluminal release of peptide YY and neuropeptide Y. Five dogs weighing 25
      kilograms had distal ileal Thiry-Vella segments of 25 centimeters surgically
      created. After a two week recovery period, each dog was tested after overnight
      fasting. The dogs were given one hour infusions of either calcium or verapamil
      after basal measurements. One hour of postinfusion measurements completed the
      study. Intravenous calcium did not affect circulating peptide YY or neuropeptide
      Y, but did significantly increase recoverable ileal peptide YY. Verapamil
      administration significantly increased both circulating peptide YY and
      neuropeptide Y levels. The results of our data suggest an independent release of
      intraluminal and intravascular peptide YY as well as modulation of the
      circulatory release of both peptide YY and neuropeptide Y by cell membrane
      calcium channel blockade.

PMID- 1994495
TI  - The value of symptom directed evaluation in the surveillance for recurrence of
      carcinoma of the breast.
AB  - Specific postoperative tests used to diagnose recurrent carcinoma of the breast
      were evaluated for their ability to have an impact on the over-all course of the
      disease. Sixty-four patients with recurrent or new contralateral primary disease
      were divided into two groups based on the method of diagnosis. Those patients
      with a new complaint at an interval between scheduled follow-up visits and who
      went on to have tests to document a recurrence were categorized as interval
      follow-up. Those who were seen at a prearranged regular follow-up period and
      received tests as recommended by the attending physician or surgeon and had a
      documented recurrence were classified as routine follow-up. Thirteen patients
      presented with new contralateral primary disease and 51 with metastatic disease
      (16, bone; 13, lung; 11, local; three, liver, and eight, multiple). The median
      time to discovery of recurrence from the primary treatment was 29 and 28 months
      for the interval and routine groups, respectively. Ninety per cent of the
      failures occurred by 53 months. The survival time after recurrence was
      significantly greater in those patients diagnosed routinely (p = 0.003). However,
      the over-all survival time (from primary therapy to death) was only significantly
      improved for the routine group when the contralateral new primary diseases were
      included (p = 0.009). The method of diagnosis of a contralateral primary
      carcinoma was physical examination and mammogram. Strong recommendations for
      follow-up testing can be limited to mammogram and physical examination.

PMID- 1994496
TI  - Trends in thirty years of vaginal hysterectomy.
AB  - Vaginal hysterectomy, as currently performed at the University of Vienna, was
      first described by Halban in 1932. From 1955 to 1985, a total of 9,967
      hysterectomies were performed. The vaginal route was used for 6,078 (60.9 per
      cent) of these procedures. Sixty-four per cent of the women operated upon were
      multiparous, 27 per cent were uniparous and 8 per cent were nulliparous. A
      comparison of the periods 1955 to 1975 and 1976 to 1985 revealed the following
      trends: the incidence of uterine myomas (30.6 to 27.1 per cent), in situ
      carcinoma of the cervix (6.5 to 7.9 per cent) and endometrial carcinoma (1.4 to
      0.6 per cent) remained largely constant. In the past decade, indications for
      positional abnormalities (uterine descent and prolapse) were encountered more
      often (27.6 to 41.6 per cent) than in the first observation period, while the
      incidence of recurrent metrorrhagia was found to decline (33.9 to 22.8 per cent).
      The most common complications included hemorrhage during the operation, lesions
      of the bladder, hemorrhage until 48 hours after surgical treatment and hemorrhage
      from days 2 to 14 postoperatively (around 0.5 per cent, respectively). During the
      second observation period, no postoperative fistulas developed. Two instances of
      tubal prolapse were seen. Laparotomy was done in four of 6,078 instances. Two
      patients died of septic complications. Whenever possible, we prefer vaginal
      hysterectomy because of its low complication rate, low mortality rate and low
      postoperative morbidity.

PMID- 1994497
TI  - Effect of portasystemic shunts on subsequent transplantation of the liver.
AB  - Portasystemic (PS) shunts have been regarded as a relative contraindication to
      hepatic transplantation (HT) because of the potential for increased technical
      difficulties during the transplant operation. We compared operative blood loss,
      morbidity and mortality in 27 patients with PS shunts and 147 patients with no
      shunts (NS) who underwent HT. The PS shunt group included 12 portocaval (PC),
      eight mesocaval, four central splenorenal and four distal splenorenal shunts. The
      PS shunt and NS groups were similar with respect to age, preoperative medical
      status and ABO blood group matching between donors and recipients. There were no
      significant differences in the mean (plus or minus S.D.) intraoperative blood
      transfusion (9.1 +/- 7.6 versus 9.2 +/- 11.0 units), mean (plus or minus S.D.)
      duration of anesthesia (8.1 +/- 1.4 versus 7.8 +/- 1.5 hours) and operative
      mortality (7 versus 11 per cent) between the PS shunt and NS groups,
      respectively. Complications of the biliary tract were significantly higher in the
      PS shunt group (22.0 versus 5.4 per cent, p less than 0.01) but they did not
      increase the mortality rate. We conclude that a prior PS shunt should not
      influence the decision to accept patients for HT. PS shunts remain a reasonable
      surgical option for patients with cirrhosis and variceal hemorrhage (refractory
      to sclerotherapy) who, by virtue of good hepatic function, do not merit immediate
      HT.

PMID- 1994499
TI  - A physician's indications for admission the night before surgery.

PMID- 1994498
TI  - Bull horn injuries.
AB  - Bull horn injury is not uncommon, and during a 12 year period from 1977 to 1988,
      101 patients required inpatient treatment at the Christian Medical College
      Hospital, a teaching hospital at Vellore in South India. The ages of these
      patients ranged from two years to 90 years and the male to female ratio was 4:1.
      Sixty-one per cent of the injuries occurred either to the perineum or abdomen and
      wounds were directed obliquely upward. Thirty-five per cent required extensive
      surgical intervention. The over-all wound infection rate was 12.9 per cent. Of
      wounds that were primarily closed, 42.9 per cent had wound infection, while only
      6.3 per cent that were secondarily closed developed infection. Two patients died
      as a consequence of the injury. Based on the results of this study, we recommend
      that a careful evaluation of the injury and timely and appropriate management of
      each patient must be done to reduce morbidity and mortality. Primary closure of
      wounds must be avoided even when surgical intervention is possible soon after
      injury.

PMID- 1994500
TI  - Technique for flow reduction in dialysis access fistulas.

PMID- 1994501
TI  - A technique for expediting the proximal anastomosis of large diameter
      polytetrafluoroethylene grafts.

PMID- 1994502
TI  - A simple technique to identify the proper vertebrae in the placement of the
      intraluminal filter in the inferior vena cava.

PMID- 1994503
TI  - Reconstruction of stenosis of the tracheostoma.

PMID- 1994505
TI  - Leadership: the nurse's role in health policy development.

PMID- 1994504
TI  - A comparative review of in situ versus reversed vein grafts in the 1980s.
AB  - In patients requiring an infrainguinal bypass who have an ipsilateral intact GSV,
      the choice between the reversed and in situ vein graft should be determined by
      the operative findings and the site of the distal anastomosis. When the
      ipsilateral GSV has either been removed or is of poor quality, ectopic autologous
      vein should be used in most circumstances and certainly for bypass to the
      infrapopliteal arteries. In reviewing the results of the two types of vein bypass
      to the popliteal artery, the results of two prospective, randomized studies and
      recent retrospective, nonrandomized reports suggest that there is no difference
      in patency rates between the two techniques. When performing a bypass to this
      level, the surgeon should not routinely use one method, but tailor the operative
      management to the individual patient. However, when the two bypass procedures to
      the infrapopliteal arteries were compared, the results of a prospective,
      randomized study and recent retrospective, nonrandomized reports furnish strong
      evidence that ISVGs provide better long term patency rates than RVGs. These
      results favoring use of distal ISVGs in nonrandomized reports are even more
      impressive, since the in situ technique was often preferentially chosen over the
      reversed vein method when only small diameter GSVs were available and when the
      bypass was performed to the distal tibial or pedal arteries. Many vascular
      surgeons agree with the conclusion that the ISVG is the bypass of choice for
      infrapopliteal bypass when an intact GSV is available. Although both the in situ
      and reversed vein techniques provide excellent long term patency rates for
      infrainguinal bypasses, and the vascular surgeon should be able to adapt this
      technique and approach for the individual patient, further randomized,
      prospective studies with extensive follow-up evaluation and a large number of
      patients are necessary to definitively resolve which technique provides optimal
      patency rates for arterial reconstruction of the lower extremity.

PMID- 1994506
TI  - [Abstracts of papers presented at the 20th Annual Meeting of the GermanSociety
      for Thoracic and Cardiovascular Surgery, Wednesday, February 20, 1991 to
      Saturday, February 23, 1991, Bonn].

PMID- 1994507
TI  - Functional deficits produced by 3-methylindole-induced olfactory mucosal damage
      revealed by a simple olfactory learning task.
AB  - Methods for assessing functional consequences of olfactory mucosal damage were
      examined in rats exposed to 3-methylindole (3-MI). Treatment with 3-MI (400
      mg/kg) induced severe degeneration of olfactory sensory epithelium followed by
      regeneration, fibrous adhesions, and osseous remodeling of the nasal passages. At
      100 mg/kg, there was mild Bowman's gland hypertrophy while the sensory epithelium
      remained intact. Rats receiving 3-MI demonstrated a treatment-related deficit in
      acquiring an olfactory learning task which was not due to altered cognitive
      abilities, as determined by subsequent testing in a step-through passive
      avoidance task. The results confirm the conclusion that alterations in functional
      indices resulted from 3-MI-induced anosmia and demonstrate the utility of simple
      learning tasks in assessing functional capacity following olfactory epithelial
      damage in rats.

PMID- 1994508
TI  - Cellular and regional distribution of reduced glutathione in the nervous system
      of the rat: histochemical localization by mercury orange and o-phthaldialdehyde
      induced histofluorescence.
AB  - Differences in the cellular distribution of antioxidant defense mechanisms in
      heterogeneous tissue such as the nervous system are likely critical determinants
      of differential sensitivity to toxicants. Regional and cellular localization of
      reduced glutathione (GSH) in central and peripheral nervous tissue was determined
      from the pattern of fluorescence observed in tissue sections stained with mercury
      orange; localization was confirmed using a novel histofluorochromatic staining
      method, o-phthaldialdehyde (OPT). Excellent concordance between the distribution
      of fluorescence obtained with mercury orange and OPT staining was observed.
      Depletion of GSH by treatment with diethyl maleate resulted in a diminution in
      both mercury orange and OPT histofluorescence. Generally, strong staining of the
      CNS neuropil was seen with little or no observable fluorescence in neuronal
      somata. The cerebellar granular cells were an exception, exhibiting fluorescence
      with both mercury orange and OPT. Cerebellar Purkinje cells exhibited nonuniform
      fluorescence with mercury orange but generally uniform staining with OPT. In
      contrast to the patterns observed in the CNS, the sciatic nerve and the sensory
      cell bodies of the lumbar dorsal root ganglia exhibited prominent fluorescence
      with both mercury orange and OPT. Reduced glutathione in the central nervous
      system appears primarily localized in the neuropil and white matter tracts; with
      a few exceptions, the neuronal somata do not appear to contain appreciable
      amounts of GSH. The heterogeneous distribution of GSH and enzymes involved in the
      detoxification and/or excretion of xenobiotics in the nervous system may form a
      basis for selective cellular and/or regional expression of neurotoxicity.

PMID- 1994509
TI  - The retention of polycyclic aromatic hydrocarbons in the bronchial airways and in
      the alveolar region--a theoretical comparison.
AB  - Several experiments indicate that physical transport phenomena such as molecular
      diffusion and partitioning between aqueous and lipid phases have a profound
      influence on the pulmonary retention of polycyclic aromatic hydrocarbons (PAHs).
      Because the average distance of diffusion between the air interface and the
      capillary blood is only about 0.5 microm in the alveoli, whereas in the bronchi
      it probably exceeds 50 microm, there should be a fundamental difference between
      the bronchial airways and the alveolar region in the retention of PAHs. A
      theoretical model was developed to simulate the retention of lipophilic
      substances in the two regions of the lung. Results show that a substance like
      benzo[a]pyrene, a PAH, may be retained for hours in the bronchi, compared to less
      than 1 min in the alveoli. This predicted dramatic difference in retention could
      explain the characteristic, biphasic pattern in the pulmonary clearance of PAHs
      observed in many animal experiments, but more importantly, it could also explain
      the fact that human lung cancers occur predominantly in the bronchi, although
      only a small fraction of inhaled particles carrying PAHs are deposited there.

PMID- 1994510
TI  - Tissue-specific changes in glutathione and cysteine after buthionine sulfoximine
      treatment of rats and the potential for artifacts in thiol levels resulting from
      tissue preparation.
AB  - L-Buthionine-S,R-sulfoximine (BSO), a potent inhibitor of gamma-glutamylcysteine
      synthetase, is commonly used as an experimental tool for the specific depletion
      of glutathione. Since cysteine is a key precursor for glutathione biosynthesis,
      we investigated the possibility that BSO might also affect the free cysteine pool
      in rat liver and kidney tissues in vivo. Male CD(SD)BR rats (150-200 g) were
      injected ip with various doses of BSO (0.25-4.0 mmol/kg), and glutathione and
      cysteine were measured in liver and kidney using HPLC with electrochemical
      detection and/or spectroscopic techniques. No hepatotoxicity or nephrotoxicity
      was observed at the highest BSO dose (4.0 mmol/kg) used. BSO caused the expected
      decreases of hepatic and renal glutathione at all doses, although glutathione
      depletion was more rapid, was achieved at a lower BSO dose, and was more
      sustained in kidney than in liver. Hepatic cysteine levels nearly doubled 20 min
      after BSO treatment (1.0 mmol/kg, ip), but were not significantly different from
      control at later time points. In contrast, renal cysteine was significantly
      depleted from 20 min to 25 hr postinjection with a time course closely
      paralleling that of renal glutathione depletion. These changes are discussed in
      the context of models for inter- and intraorgan transport of glutathione and
      cysteine. We also provide evidence that an artifact, most likely the gamma
      glutamyltranspeptidase (GGT)-initiated breakdown of glutathione, leads to a rapid
      postmortem increase of cysteine levels in liver and particularly in kidney of
      rats. Simultaneous decreases in GSH levels can be demonstrated in kidney. This
      artifact needs to be minimized in toxicological studies of glutathione and
      cysteine in kidney and other GGT-rich organs, as the measured levels of these
      thiols may not reflect the true concentrations occurring in vivo.

PMID- 1994511
TI  - Carboxylesterase-dependent cytotoxicity of dibasic esters (DBE) in rat nasal
      explants.
AB  - Dibasic esters (DBE) are a solvent mixture of dimethyl adipate (DMA), dimethyl
      glutarate (DMG), and dimethyl succinate (DMS) used in the paint and coating
      industry. Subchronic inhalation toxicity studies have demonstrated that DBE
      induce a mild degeneration of the olfactory, but not the respiratory, epithelium
      of the rat nasal cavity. Carboxylesterase-mediated hydrolysis of the individual
      dibasic esters is more efficient in olfactory than in respiratory mucosal
      homogenates. In the present study, an in vitro system of cultured rat nasal
      explants was utilized to determine if DBE toxicity is dependent on a metabolic
      activation by nonspecific carboxylesterase. Explants from both the olfactory and
      the respiratory regions of the female rat nasal cavity were incubated for 2 hr in
      Williams' medium E containing 10-100 mM DMA, DMG, or DMS. DBE caused a dose
      related increase in nasal explant acid phosphatase release, a biochemical index
      of cytotoxicity. HPLC analysis demonstrated parallel increases in the
      carboxylesterase-mediated formation of monomethyl ester metabolites. Diacid
      metabolite production in the nasal explant system was not entirely concentration
      dependent. Metabolite concentrations and acid phosphatase release were generally
      greater in olfactory than respiratory tissues. DBE-induced cytotoxicity and acid
      metabolite production were markedly attenuated in nasal tissue excised from rats
      which were pretreated with bis(p-nitrophenyl)phosphate, a carboxylesterase
      inhibitor. This study presents a viable in vitro method for assessing organic
      ester cytotoxicity in the rat nasal cavity. It was shown that DBE are weak nasal
      toxicants under the conditions of this system. It was further demonstrated that
      DBE toxicity is dependent on a carboxylesterase-mediated activation. A similar
      mechanism was proposed for the nasal toxicity induced by other organic esters
      following inhalation exposure.

PMID- 1994512
TI  - Absorption of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) after low dose dermal
      exposure.
AB  - Human dermal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) occurs
      through contact with soil and paper products. In a previous study, relative
      percutaneous absorption of TCDD increased as the dose decreased (Brewster et al.,
      1989). To determine the rate of absorption of a low dose of TCDD, absorption,
      distribution, and elimination were examined at 1, 4, 8, 12, 24, 48, 72, and 120
      hr after dermal application of 200 pmol (111 pmol/cm2) [3H]TCDD to 10-week-old
      male Fischer 344 rats. The compound was applied over a 1.8 cm2 area of the
      interscapular region of the back in 60 microliters acetone and covered with a
      perforated cap; animals were held in individual metabolism cages. Within 120 hr
      after dosing, 82 pmol (26 ng) of TCDD was absorbed. Absorption kinetics appeared
      to be first-order; the absorption rate constant was 0.005 hr-1. At each time
      point, greater than 70% of the radioactivity detected in the application site
      could be removed by swabbing with acetone. The time-related increase in the
      amount of TCDD in liver and fat closely paralleled the amount absorbed, while the
      percentage of the administered dose detected in the blood was never greater than
      0.3%. Thus, absorption of a low dose of TCDD through the skin is extremely slow
      and appears to be a first-order process.

PMID- 1994513
TI  - Murine susceptibility to organophosphorus-induced delayed neuropathy (OPIDN).
AB  - This study reports that CD-1 strain mice are neuropathologically and
      biochemically responsive to acute doses of tri-ortho-cresyl phosphate (TOCP).
      Young (25-30 g) male and female animals were exposed (po) to a single dose of
      TOCP (580-3480 mg/kg) and sampled for neurotoxic esterase (NTE) activity at 24
      and 44 hr postexposure and for neuropathic damage 14 days later. Biochemically,
      high intragroup variability existed at the lower doses, and at higher levels of
      TOCP exposure (i.e., greater than or equal to 1160 mg/kg), mean brain NTE
      inhibition never exceeded 68%. Hen and mouse brain NTE activity, assayed in vitro
      for sensitivity to inhibition by tolyl saligenin phosphate (TSP), the active
      neurotoxic metabolite of TOCP, showed similar IC50 values. Histologically, highly
      variable spinal cord damage was recorded throughout treatment groups and mean
      damage scores followed a dose-response pattern with no apparent correlation to
      threshold (i.e., greater than or equal to 65%) inhibition of brain NTE activity.
      Topographically, axonal degeneration in the mouse spinal cord predominated in the
      lateral and ventral columns of the upper cervical cord. Unlike the rat, which
      displays degeneration in the upper cervical cord's dorsal columns (i.e., gracilis
      fasciculus) in response to TOCP intoxication, treated mice showed minimal damage
      to this tract. To examine this discrepancy further, ultrastructural morphometric
      analysis of axon diameters in the cervical cord was performed in control mice and
      rats. These results indicated that in both species, the largest diameter (greater
      than or equal to 4 microns) axons are housed in the ventral columns of the
      cervical spinal cord, suggesting that axon length and diameter may not be the
      only criteria underlying fiber tract vulnerability in OPIDN.

PMID- 1994514
TI  - Development of testicular lesions in F344 rats after treatment with boric acid.
AB  - Boric acid is an inorganic acid that impairs fertility in male rodents. A
      reproductive assessment by continuous breeding study found that male rats treated
      with boric acid had decreased fertility and sperm motility. In order to determine
      the cell type that is first affected by boric acid, we have examined the
      development of the boric acid-induced testicular lesion by light and electron
      microscopy. Adult F344 male rats were fed 9000 ppm boric acid in NIH-07 rat chow
      for up to 4 weeks. The first testicular lesion noted was an inhibition of
      spermiation, which appeared by Day 7. Widespread exfoliation of apparently viable
      germ cells, and pachytene cell death in stages VII and XIV, appeared as exposure
      continued. After 28 days of dosing, extreme epithelial disorganization and germ
      cell loss were evident. To determine if there was a hormonal component to the
      boric acid-induced testicular lesion, serum levels of basal, hCG-, and LHRH
      stimulated testosterone levels were measured. After 4 days of dosing, basal
      testosterone levels were lower than controls and remained low during dosing.
      However, serum testosterone levels were similar in both boric acid-treated and
      control animals after either hCG or LHRH challenge. To determine if boron was
      preferentially accumulated by the testis, boron levels in testis, epididymis,
      liver, kidney, and blood were measured. Boron levels had effectively reached
      steady-state levels by Day 4 and were not differentially concentrated in the
      tissues examined. Thus, these studies characterize the testicular lesion produced
      by boric acid exposure and identify a decrease in basal serum testosterone levels
      in the absence of selective accumulation of boron in the testis.

PMID- 1994515
TI  - Inhibition of brain choline acetyltransferase in vivo: (E)-1-methyl-4-(1
      naphthylvinyl)-1,2,3,6-tetrahydropyridine hydrochloride (B115), a depot form of a
      potent inhibitor.
AB  - The quaternary ammonium salt (E)-4-(1-naphthylvinyl)pyridine hydroxyethyl bromide
      (B111) and the tertiary amine salt (E)-1-methyl-4-(1-naphthylvinyl)-1,2,3,6
      tetrahydropyridine hydrochloride (B115), both previously shown to protect against
      organophosphate (OP) toxicity, were examined in vivo for effects on rat brain
      choline acetyltransferase (CAT) activity and acetylcholine (ACh) levels. When
      administered iv, but not when given ip, B111 was able to inhibit brain CAT 29%
      and reduce brain ACh levels 25%, yet was unable to prevent soman-induced
      increases in ACh. B115, which may serve as a depot form of a quaternary ammonium
      analogue, was able to decrease CAT activity as much as 80% upon multiple ip
      administration. This CAT inhibitory potency was unprecedented for a tertiary
      amine salt of its structure. However, ACh levels were reduced by no more than 25%
      and B115 was ineffective in preventing soman- and sarin-induced increases in ACh.
      Since the degree of inhibition of CAT activity produced by B111 and B115 was not
      accompanied by a corresponding decrease in ACh levels, the protection afforded by
      these compounds against OP toxicity is most likely not related to CAT inhibition.
      B115 was also tested for its ability to affect cholinergic receptor binding. B115
      was administered to rats ip, twice daily, at low doses throughout a 3-week
      period. Analysis of cortex tissue revealed a 45% increase in nicotinic receptor
      binding with no change in either total muscarinic receptor binding (M-1 and M-2)
      or high-affinity muscarinic receptor binding (M-2 alone).

PMID- 1994516
TI  - Oxygen tension is a major determinant of hepatotoxicity due to 2-ethylhexanol in
      isolated tissue cylinders from periportal and pericentral regions of the liver
      lobule from phenobarbital-treated rats.
AB  - 2-Ethylhexanol, a metabolite of the commonly used plasticizer
      di(ethylhexyl)phthalate, was shown to cause toxicity exclusively to periportal
      regions of the perfused liver (Keller et al., 1990, J. Pharmacol. Exp. Ther. 252,
      1355-1360.) To determine whether this toxicity was due to local oxygen tension or
      to drug delivery, isolated cylinders (plugs) of periportal and pericentral
      regions of the liver lobule from rats pretreated with phenobarbital were
      collected with a micropunch following brief perfusion of the organ. Plugs were
      0.2 mm wide and 0.5 mm long and weighed between 0.5 and 1 mg each. Following
      incubation for at least 2 hr in Eagle's medium, they were judged viable based on
      production of urea at high rates and minimal leakage of lactate dehydrogenase
      (LDH). Plugs could be cultured for up to 24 hr with minimal loss of activity.
      Urea synthesis from ammonium chloride (3 mM) by plugs incubated in Krebs
      Henseleit buffer equilibrated with 95% O2:5% CO2 was proportional to protein
      concentration and was linear with time for up to one hour at rates around 75
      mumol/g/hr. Incubation of plugs with 2-ethylhexanol (0.1 to 3 mM) diminished urea
      synthesis in a dose-related manner (half-maximal effect = 0.5 mM). Ethylhexanol
      also caused extensive cell damage assessed from LDH leakage in incubations at 800
      microM O2 but significantly less injury at 200 microM O2. Concomitantly, urea
      synthesis was inhibited by ethylhexanol by over 80% at 800 microM O2 but less
      than 50% at 200 microM O2. Plugs isolated from both regions of the liver lobule
      were affected similarly by ethylhexanol and O2. Taken together, these data
      indicate that ethylhexanol toxicity is dependent on oxygen tension in isolated
      sublobular regions of the liver lobule, and therefore it is unlikely that drug
      delivery can explain the selective injury to periportal regions in studies with
      the perfused liver.

PMID- 1994517
TI  - Mechanism of mercurial inhibition of sodium-coupled alanine uptake in liver
      plasma membrane vesicles from Raja erinacea.
AB  - In mammalian hepatocytes the L-alanine carrier contains a sulfhydryl group that
      is essential for its activity and is inhibited by mercurials. In hepatocytes of
      the evolutionarily primitive little skate (Raja erinacea), HgCl2 inhibits Na(+)
      dependent alanine uptake and Na+/K(+)-ATPase and increase K+ permeability. To
      distinguish between direct effects of HgCl2 on the Na(+)-alanine cotransporter
      and indirect effects on membrane permeability, [3H]alanine transport was studied
      in plasma membrane vesicles. [3H]Alanine uptake was stimulated by an "out-to-in"
      Na+ but not K+ gradient and was saturable confirming the presence of Na(+)
      alanine cotransport in liver plasma membranes from this species. Preincubation of
      the vesicles with HgCl2 for 5 min reduced initial rates of Na(+)-dependent but
      not Na(+)-independent alanine uptake in a dose-dependent manner (10-200 microM).
      In the presence of equal concentrations of NaCl or KCl inside and outside of the
      vesicles, 75 microM HgCl2 directly inhibited sodium-dependent alanine-[3H]alanine
      exchange, demonstrating that HgCl2 directly affected the alanine cotransporter.
      Inhibition of Na(+)-dependent alanine uptake by 30 microM HgCl2 was reversed by
      dithiothreitol (1 mM). HgCl2 (10-30 microM) also increased initial rates of 22Na
      uptake (at 5 sec), whereas 22Na uptake rates were decreased at HgCl2
      concentrations greater than 50 microM. Higher concentrations of HgCl2 (100-200
      microM) produced nonspecific effects on vesicle integrity. These studies indicate
      that HgCl2 inhibits Na(+)-dependent alanine uptake in skate hepatocytes by three
      different concentration-dependent mechanisms: direct interaction with the
      transporters, dissipation of the driving force (Na+ gradient), and loss of
      membrane integrity. Inactivation of the Na(+)-coupled alanine carrier by mercury
      in hepatocytes of this evolutionarily primitive vertebrate, as in mammals,
      suggests that the sulfhydryl groups on this transport protein are highly
      conserved.

PMID- 1994518
TI  - MPTP-induced ATP depletion and cell death in neuroblastoma X glioma hybrid NG 108
      15 cells: protection by glucose and sensitization by tetraphenylborate.
AB  - The toxic effect of the Parkinsonism-producing neurotoxin MPTP (1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine) was investigated using a neuronal cell culture
      system, namely, neuroblastoma X glioma hybrid NG 108-15. The cells were able to
      metabolize MPTP into its active metabolite MPP+ (1-methyl-4-phenylpyridinium ion)
      and to convert its derivative, 2'-methyl MPTP, to the corresponding pyridinium
      ion. Degenerative changes were observed in NG 108-15 cells when they were
      examined with a phase-contrast microscope following exposure to MPTP, MPP+, or 2'
      methyl MPTP. These compounds also caused an increased leakage of LDH from the
      treated cells. An enhanced release of [14C]adenine nucleotides was observed from
      treated cells which were prelabeled with [14C]adenine. The cell death as
      indicated by the leakage of LDH and the release of adenine nucleotides was
      markedly reduced in the presence of a high concentration (25 mM) of glucose in
      the medium. MPTP and MPP+ induced a drastic depletion in cell ATP content prior
      to cell death. The ATP depletion was also reduced by the presence of a high
      concentration of glucose. In contrast, tetraphenylborate, a lipophilic anion,
      highly potentiated the ATP depletion and the subsequent cell death induced by
      MPTP. Thus, ATP depletion could be a major factor in MPTP-induced neuronal cell
      death.

PMID- 1994519
TI  - Organ sharing--present realities and future possibilities.

PMID- 1994520
TI  - Renal transplantation from elderly living donors.
AB  - A worldwide shortage of cadaveric donors has led to the increased utilization of
      elderly living donors, with controversial results. In an attempt to assess the
      effect of donor age on graft survival and subsequent renal function, we analyzed
      our clinical results in 276 consecutive recipients of living related renal
      transplants spanning both the cyclosporine and the azathioprine eras, of whom a
      total of 44 recipients received kidneys from donors over 55 years old. All
      recipients were otherwise similar in age, race, haplotype mismatch, number of
      retransplants, and number of pretransplant transfusions, apart from an increased
      number of diabetics among the CsA-treated recipients of elderly kidneys (38% vs.
      14%). The cumulative patient and graft survival rates at 1 and 5 years were
      independent of donor age whether CsA or AZA was utilized. Nor was the incidence
      of rejection or infection significantly different in the older donor group when
      compared with the younger cohort. Short-term and intermediate-term renal
      function, as assessed by serum creatinine, was however poorer but stable in the
      older donor group when compared with the younger one. The mean serum creatinine
      levels at 1 year in the CsA- and AZA-treated recipients of kidneys from older
      donors were 2.4 and 2.0 mg/dl, respectively, compared with 1.6 and 1.4 mg/dl,
      respectively, when the donor age was less than 55 years (P less than 0.001).
      Since renal function at the end of the first posttransplant year is considered a
      determinant of long-term graft survival, this is a cause for concern, but in view
      of the universal shortage of organs and the negligible morbidity to donors, renal
      transplantation from elderly living donors remains an acceptable practice.

PMID- 1994521
TI  - Endomyocardial biopsies in pediatric patients with no irradiation. Use of
      internal jugular venous approach and echocardiographic guidance.
AB  - Heart transplants in pediatric patients have moved from an experimental, end
      stage treatment to a valuable therapy for inoperable congenital heart disease and
      dilated cardiomyopathies. Cardiac rejection is a frequent problem in children
      with heart transplants. The technical difficulties of obtaining biopsies in small
      children have encouraged the use of noninvasive methods of detection although
      endomyocardial biopsy continues to be the most reliable method of surveillance
      for cardiac rejection. We examined our experience over 7 years with 4 patients
      (ages 8 months to 10 years) who had a total of 88 endomyocardial biopsies using
      echocardiographic guidance. The biopsies were done using a Caves-Schultz biotome
      via the right internal jugular vein. Biopsies were performed in the procedure
      room, 61%; pediatric intensive care unit, 18%; hospital private room, 18%; and
      catheterization laboratory, 3% of the time. At 5.0, 6.5, or 8.5 French biotome
      was used depending on the size of the patient. Twelve episodes of rejection were
      detected in these patients. The time for venous access was 17 +/- 15 min, and the
      biopsies took 25 +/- 11 min using this approach. Biopsies were obtained from the
      right ventricular free wall, apex, and septum to detect focal rejection for a
      total of 4-6 tissue samples per biopsy. Neither general anesthesia nor
      fluoroscopy was needed for these biopsies. Costs ranged from $1120 in the patient
      room to $1590 in the pediatric intensive care unit. Five different biopsies using
      a femoral approach with fluoroscopic guidance averaged $2250 and did not include
      the functional assessment obtained using echocardiography. Using the
      echocardiogram one can see the ventricular muscle and completely avoid
      perforation. Thus, this technique is technically feasible in children with few
      complications at a reduced cost, compared to fluoroscopically guided biopsies.

PMID- 1994522
TI  - AHG and DTE/AHG procedure identification of crossmatch-appropriate donor
      recipient pairings that result in improved graft survival.
AB  - We compared our standard NIH (extended incubation) crossmatch (XM) with antihuman
      globulin (AHG) and flow cytometry crossmatches (FCXM) and correlated the results
      with primary cadaveric and retransplant graft survivals. In addition, we treated
      the XM sera with the reducing reagent dithioerythritol (DTE) to discriminate IgM
      from IgG immunoglobulin reactivity. For the 166 CsA-Pred-treated primary
      cadaveric renal allograft recipients the 1-year graft survival rate following an
      NIH-NEG XM was 81%. NIH-XM-NEG recipients who were also AHG-XM-NEG displayed an
      82% 1-year graft survival as well. In contrast, NIH-NEG, but AHG-POS XM primary
      CAD recipients displayed a significantly reduced graft survival rate of 67%.
      Treatment of AHG-POS XM sera with DTE-delineated DTE/AHG-NEG and POS crossmatches
      associated with significantly different graft survivals of 83% and 0%,
      respectively, for these primary recipients. Flow cytometry XM results did not
      improve on the AHG-NEG or DTE/AHG-NEG XM primary graft survivals. These results
      were seen whether testing pre-Tx or historical (Hx) sera. For Re-Tx recipients an
      AHG-NEG XM resulted in significantly improved graft survival compared with the
      NIH-XM-NEG results. The overall 1-year graft survival rate for the 70 Re-Tx
      recipients studied was 64% (following a NEG pre-Tx NIH-XM). Re-Tx recipients with
      an AHG-NEG XM displayed an improved graft survival compared with NIH-XM-NEG
      recipients (77% vs. 64%, P less than 0.05) and with AHG-POS recipients (77% vs.
      36%, P less than 0.01). However, treatment of Re-Tx, AHG-POS sera with DTE
      resulted in comparably poor graft survival rates of 31% and 50% for DTE/AHG-NEG
      and POS crossmatches, respectively. A FCXM did not improve on the results of Re
      Tx graft survival following an AHG-NEG XM. These results were obtained whether
      testing pre-Tx or Hx sera. HLA matching, PRA, and the time the first Tx was lost
      did not influence the Re-Tx graft survival outcome following an AHG-NEG XM.
      Therefore, successful primary cadaveric renal allograft survival can be
      accomplished following either an AHG-NEG XM or an AHG-DTE-NEG XM. Re-Tx graft
      survival is significantly improved following an AHG-NEG XM. Re-Tx recipients with
      an AHG-POS XM who are either DTE/AHG-POS or -NEG display reduced graft survivals
      compared with AHG-NEG Re-Tx recipients.

PMID- 1994523
TI  - Removal of lymphocytotoxic antibodies by pretransplant immunoadsorption therapy
      in highly sensitized renal transplant recipients.
AB  - A high level of panel-reactive antibodies (PRA) in potential renal transplant
      recipients is associated with a long waiting time until transplantation and
      correlates inversely with graft outcome. We report our experience with the
      employment of immunoadsorption (IA) using a column composed to sepharose-bound
      staphylococcal protein A (which has a relatively selective affinity for binding
      IgG compared with other immunoglobulins) to decrease the PRA levels and expedite
      transplantation in 6 highly sensitized potential renal transplant recipients (1
      primary and 5 awaiting second transplants). All patients had PRA levels of
      greater than or equal to 70% for a duration of 1 year prior to IA. Only patients
      with antibody specificity localized to 1 or 2 HLA A or B antigens were accepted
      for the study. IA procedures were performed on alternate days until a twofold
      decrease in antibody titer had occurred (maximum: 6 procedures). Repeat
      procedures were initiated if the HLA antibody titer returned to its baseline
      value. Intravenous cyclophosphamide (CY) (10 mg/kg/day every 3 weeks) and
      methylprednisolone (MP) (0.5 mg/kg/day) were provided as adjunctive
      immunosuppression until transplantation. A total of 44 immunoadsorption
      procedures were performed (27 primary and 17 repeat) with treatment of 2.49 +/-
      0.02 plasma volumes per session. Serum IgG concentration decreased 95 +/- 3% and
      PRA activity decreased 75 +/- 16% after the primary treatment course. Four
      patients received cadaveric grafts within 3.7 +/- 1.2 months following the last
      IA procedure. Three grafts are functioning at 1 year, 8 months, and 8 weeks
      posttransplant. The remaining graft demonstrated primary nonfunction. All four
      patients had a past positive crossmatch using pre-IA sera with their respective
      donors. Patients not transplanted exhibited rapid resynthesis of IgG and a return
      of the PRA towards baseline levels within a few weeks after IA. We conclude that
      IA can effectively remove HLA antibodies and expedite graft availability in
      highly sensitized patients.

PMID- 1994524
TI  - The variable nature of chronic declines in renal allograft function.
AB  - Despite having important implications for the design of therapeutic trials, the
      clinical setting, time of onset, and rate of progression for chronic declines in
      renal allograft function have not been well characterized. In the present
      investigation, monthly estimates of glomerular filtration rate (E-GFR) were made
      using creatinine clearance and interim serum creatinine levels. There were 200
      patients transplanted from 1978 to 1982 (precyclosporine) who survived at least
      12 months with a functioning allograft. Of these, 25 had irreversible declines in
      E-GFR (greater than 30%) attributable to acute rejection, 50 had gradual, chronic
      declines in E-GFR, and 125 maintained stable function. Patients with chronic
      declines in E-GFR more often returned to dialysis (56%, P less than 0.001) than
      those with irreversible, acute reductions (24%), or stable function (2%). Chronic
      declines in allograft function were modeled by one or two least-squares-fitted
      regression lines. In most cases, the onset was early, but in 26% chronic declines
      in E-GFR began 2.2 +/- 1.2 (mean +/- SD) years after transplantation. Among those
      with chronic declines in E-GFR, 20/50 (40%) had spontaneous improvements in the
      rate of progression after 2.7 +/- 1.1 years and survived 8.4 +/- 2.6 years with
      functioning grafts, while 30/50 (60%) continued to have progressive declines in E
      GFR and survived 6.1 +/- 2.5 years (P less than 0.01). Although chronic declines
      in E-GFR were evident 3.2 +/- 1.7 years before graft failure, routinely measured
      clinical and laboratory parameters from the early posttransplant period failed to
      predict patients who developed chronic declines in E-GFR. Altogether these data
      suggest that chronic declines in allograft function have an unpredictable onset
      and variable clinical course.

PMID- 1994525
TI  - Diabetes mellitus after renal transplantation in the cyclosporine era--an
      analysis of risk factors.
AB  - Despite mounting experimental evidence that cyclosporine inhibits pancreatic
      islet cell function, clinical data on posttransplant diabetes mellitus (PTDM) in
      renal allograft recipients in the cyclosporine era are scarce. Between June 1983
      and December 1988, 39 of 337 (11.6%) cyclosporine-treated adult renal transplant
      recipient whose grafts survived longer than 1 year developed PTDM. Of these,
      43.6% and 74.4% were diagnosed by 3 and 12 months posttransplant, respectively,
      and 51.3% were insulin-dependent. Incidence of PTDM was highest in blacks (19.8%)
      and Hispanics (21.3%) and in those with HLA-A 30 and Bw 42 antigens. Older
      recipients and those that received cadaveric kidneys were more likely to develop
      diabetes than those who received living related allografts (14% vs. 5.3%, P less
      than 0.05). The rate of PTDM appeared to be independent of the type of induction,
      immunosuppressant therapy, incidence of rejection, total steroid and cyclosporine
      dose, percentage of body weight gain in the first posttransplant year, and serum
      creatinine concentration. Actuarial 5-year, decaying from 100% at 1 year, patient
      and graft survival rates were 87% and 70%, respectively, in the PTDM group
      compared with 93% and 90%, respectively, in controls. Causes of graft failure
      among the diabetics included chronic rejection (6), patient death (3),
      noncompliance with immunosuppressants (2), and sepsis (1). The incidence of
      infectious complications was significantly higher in the PTDM group compared with
      the control group (53% vs. 16%, P less than 0.05), with all 5 deaths among the
      diabetics being sepsis-related.

PMID- 1994526
TI  - HLA matching at a single kidney transplant center.
AB  - Over 1000 patients were analyzed in two different time intervals, 1978-1983 and
      1984-1989; these corresponded to patient groups not treated with cyclosporine and
      treated with cyclosporine. Analysis of mismatching showed that there was a
      significant (P less than 0.05) longterm matching effect in the precyclosporine,
      era with 0 HLA-DR-mismatched recipients having a 9.5-year half-life compared with
      a 3-year half-life for the 2 HLA-DR-mismatched transplant recipients. The trend
      was similar for the cyclosporine-treated groups, but not significant. Risk
      factors for donor age and race of the recipient (P less than 0.05) were
      identified in the cyclosporine-treated group. Graft survival in the high-risk
      patient populations was 70% or better in the 0, 1 HLA-ABDR-mismatched groups as
      compared with less than 60% graft survival in the high-risk transplant recipients
      with 2-6 HLA-ABDR mismatches. In the cyclosporine era the HLA-ABDR 0, 1
      mismatched patient groups showed a significantly better graft survival than was
      found in all other categories and at all time intervals analyzed. Matching is a
      way to ameliorate some of the high risk potential associated with less than
      optimal donor or recipients.

PMID- 1994527
TI  - Chronic rejection in primary renal allograft recipients under cyclosporine
      prednisone immunosuppressive therapy.
AB  - Although the introduction of cyclosporine-prednisone immunosuppression has
      improved early renal graft survival, chronic rejection remains a major cause of
      longterm graft dysfunction. This study retrospectively examined 69 cases of
      chronic rejection among 643 primary renal allograft recipients treated with
      cyclosporine-prednisone immunosuppression from July 1981 to October 1989. Chronic
      rejection was defined as a rejection episode diagnosed greater than 90 days
      posttransplantation with characteristics of progressive nonacute renal function
      deterioration, confirmed, in most cases, by renal biopsy. This group was compared
      with an equal-sized matched cohort. Among cadaveric recipients, 61 of 456
      patients (13.4%) displayed chronic rejection, whereas among living-related
      recipients, 8 of 187 patients (4.3%) developed chronic rejection. The average
      time from the date of transplantation to diagnosis of chronic rejection was 15 +/
      14 months. One- and three-year graft survivals following diagnosis of chronic
      rejection were 51% (30/59) and 25% (13/51), respectively, compared with the
      cohort one- and three-year graft survivals of 98% (58/59) and 86% (32/37) at
      similar periods posttransplantation. HLA mismatch, PRA status, blood transfusion
      history, lipid levels, cyclosporine trough levels, incidence of prior acute
      rejection, and initial graft dysfunction were not significantly different between
      the chronic rejection group and the matched cohort. Hypertension and proteinuria
      were significantly associated with chronic rejection (P less than 0.001). Of 58
      biopsies performed, findings solely consistent with chronic rejection were
      observed in 9 cases (15%) and "acute upon chronic" rejection in 49 cases (83%).
      Treatment of acute concomitants improved the renal function in 43% (27/63) by the
      time of hospital discharge. Nonetheless, at 12 months the incidence of improved
      renal function eroded to 22% (13/59), suggesting that the benefit was relatively
      short-lived. Although the overall incidence of chronic rejection in this group of
      cyclosporine-prednisone-treated patients was lower than previous azathioprine
      prednisone cohorts, the clinical presentation and progression of chronic
      rejection was similar. Additionally, the incidence of chronic rejection within
      this series was lower among living-related recipients versus cadaveric recipients
      of donor organs.

PMID- 1994528
TI  - The beneficial effect of blood transfusion and the DR 1 gene dose on renal
      transplant outcome in blacks.
AB  - We performed a retrospective analysis of the factors determining renal allograft
      survival in 70 black recipients from a single center and 1212 black recipients
      from multicenter registry data. One and two-year graft survival in single-center
      blacks was comparable to the result achieved in the general population (81% and
      77%, respectively). Two-year graft survival in multicenter blacks was
      significantly worse than nonblacks (73% versus 55%, respectively; P less than
      0.01). Graft survival in untransfused blacks receiving cyclosporine was no better
      than the result achieved during the azathioprine era. A beneficial effect upon
      graft survival was seen in blacks transplanted at the centers that have
      consistently displayed the best overall allograft survival over the years.
      Matching for HLA antigens was consistently poorer in blacks compared with whites
      and did not confer additive benefit over cyclosporine and blood transfusion. Our
      data indicate that cyclosporine immunosuppression, blood transfusion, and
      individual center expertise contribute significantly toward optimal transplant
      outcome in the higher-risk black end-stage renal disease population.

PMID- 1994529
TI  - Cyclosporine dose reduction by ketoconazole administration in renal transplant
      recipients.
AB  - Cyclosporine metabolism occurs in the liver via hepatic cytochrome P-450
      microsomal enzymes. Ketoconazole, an imidazole derivative, has been shown to
      inhibit the cytochrome P-450 enzyme system. Thirty-six renal transplant
      recipients receiving cyclosporine as part of a triple immunosuppressive drug
      regimen were started on 200 mg/day of oral ketoconazole. The dose of cyclosporine
      was reduced by 70% at the start of ketoconazole; this dose reduction was based on
      our previous experience with concomitant cyclosporine-ketoconazole therapy.
      Ketoconazole was started in patients who had been on cyclosporine for between 10
      days and 74 months. The mean cyclosporine dose was 420 mg/day (5.9 mg/kg/day)
      before starting ketoconazole and 66 mg/day (0.9 mg/kg/day) one year after the
      addition of ketoconazole; this represents a cyclosporine dose reduction of 84.7%
      (P less than 0.0001). The mean trough whole-blood cyclosporine concentrations
      measured by HPLC, were 130 ng/mL preketoconazole and 149 ng/mL after 1 year of
      combination therapy. Mean serum creatinine and BUN levels were unchanged before
      and during ketoconazole administration, and no changes in liver function tests
      were noted. Cyclosporine pharmacokinetics were performed before and after at
      least three weeks of ketoconazole. Hourly whole-blood samples were measured by
      HPLC (parent cyclosporine only) and TDX (parent + metabolites). Combination
      therapy resulted in decreases in the maximum blood concentration and the steady
      state volume of distribution divided by the fractional absorption, and increases
      in mean residence time and the parent-to-parent plus metabolite ratio (calculated
      by dividing the HPLC by the TDX value). The addition of ketoconazole to
      cyclosporine-treated patients resulted in a significant inhibition of
      cyclosporine metabolism and decrease in the dosage. There was minimal
      nephrotoxicity, and only four rejection episodes occurred on combined therapy.
      The concomitant administration of the two drugs was well tolerated, and there was
      no deleterious effect on the immunosuppressive activity of cyclosporine. This
      drug interaction provides a significant reduction in the costs associated with
      organ transplantation.

PMID- 1994530
TI  - Alloantibodies against donor epidermis and early kidney transplant rejection.
AB  - We have previously observed that transplant recipient sera with endothelial
      antibodies are bound to epidermal cells, as shown by immunofluorescence on
      sections of skin. It was also reported that early kidney failures that occurred
      despite negative T cell crossmatches were associated with, and could have been
      predicted by, a crossmatch with donor skin. Ninety patients undergoing kidney
      transplantation have now been evaluated using this technique. A few other
      patients were excluded from the analysis because of the presence of
      autoantibodies staining autologous skin. In 12 the crossmatch with donor skin was
      positive, and 9 of them had severe rejection within the first 10 days after
      transplantation. The three patients with a positive skin crossmatch and a benign
      course had not been tested with autologous skin and therefore autoantibodies
      could not be excluded. Only 7 of the 78 patients with negative skin crossmatches
      had early rejection. The correlation between skin crossmatch and early rejection
      was statistically highly significant (P less than 0.0001). Studies by flow
      cytometry have shown that these antigens are found on the surface of epidermal
      and endothelial cells, and are modulated by gamma interferon. When tested against
      a panel of skin donors, skin alloantibodies gave different patterns of positive
      and negative reactions, suggesting polymorphism.

PMID- 1994531
TI  - Effects of steroid withdrawal on posttransplant diabetes mellitus in cyclosporine
      treated renal transplant recipients.
AB  - Posttransplant diabetes mellitus (PTDM) traditionally has been attributed to
      therapy with steroids--however, several lines of evidence suggest that
      cyclosporine also is diabetogenic. A retrospective review revealed that PTDM
      developed in 9 of 70 previously nondiabetic kidney transplant recipients (12.9%)
      maintained on prednisone, azathioprine, and CsA compared with 8 of 83
      nondiabetics (9.6%) maintained on azathioprine and prednisone alone in an earlier
      era (P = NS). Among patients maintained on triple-drug therapy, complete
      withdrawal of prednisone was attempted in 7 renal transplant recipients with PTDM
      and in 1 recipient of a combined kidney-pancreas transplant who exhibited
      evidence of type II diabetes mellitus. Seven of the 8 patients were able to
      discontinue insulin or oral hypoglycemic agents within 4 months of discontinuing
      steroids. Mean glycohemoglobin level declined from 10.6 +/- 3.6% prior to steroid
      withdrawal to 6.0 +/- 1.3% within 1 month of steroid cessation, while mean CsA
      dose and trough CsA blood levels remained unchanged. In 2 patients, mild
      rejection episodes prompted a return to steroid therapy. Although CsA may be
      diabetogenic, evidence from this study suggests that withdrawal of steroid
      therapy is a safe and effective approach to the management of PTDM in patients
      subsequently maintained on CsA and azathioprine.

PMID- 1994532
TI  - Multivariate analysis of donor-specific versus random transfusion protocols in
      haploidentical living-related transplants.
AB  - A total of 127 haploidentical living-related transplants have been performed at
      our institution since March 1986. A donor-specific transfusion plus azathioprine
      protocol was used until July 1988 (n = 74) and a random transfusion (RT) protocol
      without AZA used thereafter (n = 53) in an effort to decrease risk of recipient
      sensitization and reduce the burden on the prospective donor. All patients were
      given cyclosporine 8 mg/kg/day orally beginning 1 week prior to transplantation.
      Immunosuppression was similar in both groups and consisted of triple induction
      therapy with prednisone, CsA, and AZA. A positive T cell crossmatch eliminated
      the potential donor. Seven individuals (9.6%) were sensitized in the DST group
      and 1 (1.9%) in the RT group, leaving 67 and 52 patients in the two groups of the
      study, respectively. Groups were similar with respect to age, sex, history of
      pregnancy in female patients, peak and baseline panel-reactive antibody (PRA), DR
      match, and prior transplants. The groups differed slightly with respect to AB
      antigens shared, with an advantage in the RT group. Actuarial graft survival was
      not statistically significantly different between the two groups, with 2-year
      graft survival of 95% in the DST and 91% in the RT group (log rank, P = 0.16).
      Patients in the RT group had significantly more rejection episodes and had them
      sooner than their counterparts in the DST group. At the end of 1 year, 50% of
      patients in the DST group had at least 1 rejection episode, compared with 75% of
      patients in the RT group (P = 0.0008). Multivariate (Poisson) analysis of 10
      variables was performed, with an overall model P-value of 0.0001. Only DST (P =
      0.0001) and pregnancy (P = 0.015) were significant predictors of rejection
      episodes, both protective. The difference in rejection episodes and the timing
      with which they occur has not yet translated into a significant difference in
      graft survival between DST and RT groups.

PMID- 1994533
TI  - Variability in the morphological spectrum and clinical outcome of chronic liver
      disease in hepatitis B-positive and B-negative renal transplant recipients.
AB  - The impact of hepatitis B infection on the clinical outcome of renal
      transplantation has been controversial. Some investigators reported excess
      mortality from hepatic failure and/or concurrent sepsis while others found no
      such detrimental effect. Since the clinical or biochemical data do not reflect
      the severity or the course of liver disease in these immunosuppressed patients,
      we performed percutaneous liver biopsies and systematically analyzed the
      histological findings in 68 patients who had clinical evidence of chronic liver
      disease in the posttransplant period. Twenty-six of these patients were HBs Ag
      positive and 42 were HBs Ag-negative. There were no significant differences in
      the demographic data, biochemical variables, or the mean follow-up between the
      two groups. RESULTS: HBs Ag-positive patients had more severe histological forms
      of liver disease, i.e., chronic persistent hepatitis (CPH) (38%) and chronic
      active hepatitis (CAH) (38%), compared with 17% CPH and 14% CAH in HBs Ag
      negative patients (CPH, P = 0.08; CAH, P = 0.04). The incidence of cirrhosis was
      also higher in the HBs Ag-positive patients (42% vs. 19%, P = 0.07). During a
      mean follow-up of 82 +/- 58 months from the onset of hepatitis, 54% of hepatitis
      B-positive patients died from liver failure compared with 12% of the B-negative
      group, who were followed for a mean period of 74 +/- 47 months from the onset of
      hepatitis. The difference in mortality rate was highly significant (P = 0.002).
      Comparison of initial histology with a follow-up specimen in 25 patients (13 HBs
      Ag-positive, 12 HBs Ag-negative) also showed a trend towards higher frequency of
      liver cirrhosis in the B-positive patients compared with the B-negative group (P
      = NS). Our observations, based on liver histology, confirm earlier reports that
      hepatitis B infection is associated with a bad prognosis in renal allograft
      recipients, who have clinical evidence of chronic liver disease.

PMID- 1994534
TI  - Incidence, treatment, and outcome of recurrent focal segmental glomerulosclerosis
      posttransplantation in 42 allografts in children--a single-center experience.
AB  - Steroid-resistant FSGS and its recurrence posttransplantation are predominantly
      seen in children. We report on the largest pediatric transplant population for
      FSGS with similar numbers of azathioprine- and cyclosporine-treated patients
      analyzed for recurrence. Of 70 patients with idiopathic FSGS identified over the
      years 1974-1989, 49 progressed to end-stage renal disease and 28 received 42
      transplants (17 live-related donors, 25 cadaveric). Seventeen patients each
      received one transplant, 9 patients each received two transplants, and one
      patient each received three and four transplants. The mean age at diagnosis of
      FSGS was 9.1 +/- 4.2 years, the mean duration of FSGS prior to reaching ESRD was
      2.2 +/- 1.3 years, and the mean duration on dialysis prior to transplantation was
      9.7 +/- 6.3 months. Primary nonfunction was observed in 2 transplants; in the
      remaining 40 transplants, 6 recurrences were noted (15%). Recurrences were noted
      in four AZA and prednisone (n = 22) and two CsA and prednisone (n = 18)
      recipients. Risk factors analyzed for recurrence included race, age at FSGS,
      histological and clinical severity of FSGS, classification of FSGS, duration of
      disease, interval on dialysis, multiple transplants, and HLA matching. Only age
      at onset of FSGS was predictive of recurrence. The incidence of recurrence was
      higher in children less than or equal to 6 years of age compared with those over
      6 years (P less than .05). All 4 patients receiving AZA and prednisone went on to
      lose their grafts due to recurrence. Recurrent proteinuria in the 2 CsA and
      prednisone recipients was controlled by gradually increasing the CsA dose from 15
      mg/kg/day to 27 and 35 mg/kg/day. Remission of the nephrotic syndrome was induced
      within 60 days in both patients. Presently, both grafts are functioning 24 and 16
      months posttransplant with serum creatinines of 0.9 and 0.5 mg/dl, respectively.
      We conclude that recurrence is predominantly seen in very young children and
      occurs even under CsA immunosuppression. High-dose CsA may control the recurrent
      proteinuria--however, the long-term outcome of such intense therapy is not known.

PMID- 1994535
TI  - Graft thrombosis in pediatric renal transplant recipients. A report of the North
      American Pediatric Renal Transplant Cooperative Study.
AB  - Data from the North American Pediatric Renal Transplant Cooperative Study were
      analyzed to determine the incidence and possible causes of graft thrombosis in
      pediatric renal transplant recipients. Between January 1987, and November 1989,
      1045 renal transplants in recipients less than 18 years of age were registered in
      the study, including 484 living-related donor and 561 cadaver donor transplants.
      There were 213 graft failures (67 LRD, 146 CAD), and of these 27 were caused by
      thrombosis (8 LRD, 19 CAD). Thrombosis occurred in 2.6% of all transplants and
      accounted for 22.5% (27/120) of all graft failures that occurred in the first 60
      days following transplantation. Among the LRD recipients, there were 24 graft
      failures in those less than 6 years of age, and 7 of these were due to
      thrombosis, compared to 1 thrombosis in 43 graft losses in recipients greater
      than 6 years (P less than 0.01). In recipients less than 6 years old, the
      thrombosis rate for those who received transplants without prior dialysis was
      4/32 (12.5%) versus 3/109 (2.8%) with prior dialysis. Among the CAD recipients,
      age of the recipient did not influence graft thrombosis. Donor age, however, was
      strongly associated with the risk of thrombosis, as was cold storage time. Donor
      age and cold storage time were not independently distributed within the
      population, with longer cold storage times required for younger donors. Both
      factors, however, independently affected outcome. Other factors, including prior
      nephrectomy, prior transplant, center size, and use of cyclosporine were not
      associated with increased risk of thrombosis in LRD or CAD recipients. We
      conclude that graft thrombosis is an important cause of renal graft loss in
      children. In LRD transplants the risk of graft thrombosis is increased in
      recipients less than 6 years old, and preliminary data suggest that the lack of
      prior dialysis may be associated with thrombotic risk in these patients. CAD
      transplant recipients who receive grafts from young donors, particularly those
      with long cold storage time, are at increased risk for graft failure due to
      thrombosis.

PMID- 1994536
TI  - Long-term patient survival in a pediatric renal transplantation program.
AB  - In adult renal transplant recipients, reports have shown continuing mortality
      beyond 5 years after transplantation with the majority of deaths due to
      myocardial infarctions, malignancies, and liver failure. Little information is
      available on the long-term survival of children following renal transplantation.
      Children with end-stage renal disease have fewer systemic complications than
      adults and should have better long-term survival. Furthermore, analysis of
      mortality in the pediatric population should be more informative of the risks of
      renal transplantation, separate from underlying pretransplant diseases and the
      inherent complications of aging. We analyzed, therefore, the long-term mortality
      of renal transplant recipients in a single pediatric center. A total of 299 renal
      transplants were performed in 251 patients from 1971 through 1990. No patient was
      excluded from the evaluation. Over all, actuarial survival was 91% at 1 year, 83%
      at 10 years, and 81% at 15 years. Patient's age at transplantation, donor source,
      and number of previous allografts were not correlated with patient survival.
      There were 35 deaths with 51% attributable to infections. The majority of deaths
      (71%) occurred within the first 6 months after renal transplantation during the
      period of greatest immunosuppression. Mortality within the first 12 months
      following renal transplantation was higher during the period 1971-1974 when
      compared to subsequent years. These data demonstrate that in a pediatric renal
      transplant center, long-term patient survival is excellent. Most deaths occur
      within the first 6 months following renal transplantation and are caused by
      infections. As expected, long-term survival in children is better than reports in
      adult renal transplant recipients and may more accurately reflect true renal
      transplant-related mortality.

PMID- 1994537
TI  - Perioperative renal function in patients undergoing orthotopic liver
      transplantation. A randomized trial of the effects of verapamil.
AB  - Patients who undergo orthotopic liver transplantation often experience a
      significant drop in GFR postoperatively. Postulated mechanisms include
      intraoperative hemodynamic changes, suboptimal renal perfusion during the
      anhepatic stage, and cyclosporine administration. We undertook a prospective
      double-blind study to investigate these factors, as well as to determine the
      protective effects of verapamil on perioperative renal function. Twenty-five
      patients with normal renal function undergoing OLT received either placebo (n =
      13) or verapamil (n = 12) intraoperatively and for six weeks post-OLT. No CsA was
      administered until after reperfusion of the graft liver, and venovenous bypass
      (VVB) was utilized in all cases. Patients completing six weeks of the study
      experienced 61% and 48% decreases in GFR within the placebo and verapamil groups
      respectively. A significant decrease in GFR occurred in the placebo group between
      one and six weeks post-OLT, and a significant drop in GFR occurred in the
      verapamil group by one week post-OLT. Differences between the groups were not
      significant, however. Systemic, renal, and hepatic hemodynamics were similar at
      all times between groups, and renal hemodynamics and urine output were unchanged
      during VVB. We conclude that (1) perioperative factors do not contribute to renal
      dysfunction post-OLT when VVB is used; (2) VVB preserves renal hemodynamics
      during the anhepatic phase; (3) CsA is the most likely causative agent for post
      OLT renal dysfunction; and (4) intraoperative verapamil serves no protective
      role, as administered in this study.

PMID- 1994538
TI  - Long-term survival and renal function following liver transplantation in patients
      with and without hepatorenal syndrome--experience in 300 patients.
AB  - We have retrospectively reviewed the first 308 patients undergoing orthotopic
      liver transplantation (OLTX) at our institution to determine the following: 1) To
      what extent does renal function deteriorate postoperatively? 2) To what extent
      does renal function recover after OLTX for hepatorenal syndrome (HRS)? 3) What is
      the survival rate of patients with HRS compared with those without HRS? In non
      HRS patients, GFR declined from 97.1 +/- 2.9 cc/min to 56.6 +/- 2.4 cc/min at 6
      weeks postoperative, 62.6 +/- 2.6 cc/min at 1 year, and 58.3 +/- 3.5 cc/min at 2
      years. In HRS patients, GFR increased from 19.9 +/- 3.6 cc/min to 32.5 +/- 3.1
      cc/min at 6 weeks, 45.9 +/- 5.5 cc/min at 1 year, and 37.9 +/- 5.9 cc/min at 2
      years. Dosages of cyclosporine were comparable in both groups. There was no
      difference in perioperative (90-day) mortality. One- and 2-year actuarial
      survival rates in the non-HRS patients were 87.2% and 82.1%, respectively. The
      actuarial 1- and 2-year survival rate for the HRS patients was 76.6% (P = NS).
      Ten percent of HRS patients developed ESRD posttransplant compared with 0.8% of
      non-HRS patients (P less than 0.005). We conclude that patients with HRS can
      safely undergo OLTX with acceptable perioperative mortality and good long-term
      survival. Most HRS patients have return of acceptable renal function. Patients
      without HRS have a severe decline in GFR posttransplant, which is stable up to 3
      years posttransplant.

PMID- 1994539
TI  - Orthotopic liver transplantation in patients 60 years of age and older.
AB  - Cyclosporine appears to have abrogated age as a contraindication to kidney
      transplantation in the elderly, although it is unclear whether this is true for
      other types of solid organ transplantation. We performed a retrospective analysis
      of liver transplant recipients who were 60 years of age and older (n = 23) versus
      recipients of primary transplants who were 18 to 59 years of age (n = 84).
      Indications in recipients over 60 included alcoholism (6), postnecrotic cirrhosis
      (6), cancer (4), primary biliary cirrhosis (3), sclerosing cholangitis (2), and
      one patient with polycystic liver disease. There were no important differences in
      the initial transplant hospitalization or the incidence of infection and
      rejection between the two groups. No patient in the over-60 population required
      retransplantation. Actuarial patient survival is 83% at 2 years for recipients 60
      years of age and above compared to 76% patient survival in adult recipients who
      are under the age of 60. Liver transplant recipients over the age of 60 years
      have excellent patient and graft survival and the same postoperative morbidity as
      recipients who are under 60 years of age. Therefore, advanced age does not appear
      to be a contraindication to orthotopic liver transplantation.

PMID- 1994540
TI  - Detection of allograft endothelial cells of recipient origin following ABO
      compatible, nonidentical cardiac transplantation.
AB  - Endothelial cells serve an important role in augmenting immune responses through
      enhanced expression of MHC class II antigens. Immune-mediated vascular injury
      associated with rejection requires reendothelialization to restore vascular
      integrity. The origin of the reparative endothelial cells can be determined when
      ABO antigens expressed on these cells differ in the donor and recipient. To
      assess the frequency and significance of reendothelialization by recipient
      endothelial cells, we stained serial endomyocardial biopsies for ABO antigens in
      34 (13%) compatible, nonidentical cardiac allograft recipients of 268 cardiac
      transplant procedures. In ten (30%) the allograft endothelial cells expressed the
      characteristics of the recipient (five partial and five complete) within 7.5 +/-
      1.0 months (mean +/- SEM) after transplantation. Over 26.3 +/- 2.5 months follow
      up no differences could be detected in pretransplant characteristics, allograft
      survival, survivor rejection morbidity, long-term allograft function, and
      presence of coronary vasculopathy between those whose endothelial cells expressed
      recipient blood group antigens and those who did not, which may merely be a
      reflection of the small sample size. This study indicates that recipient
      reendothelialization occurs frequently following cardiac transplantation and may
      result from immune-mediated vascular injury. The effect of recipient
      reendothelialization on allograft tolerance requires further investigation.

PMID- 1994541
TI  - Marrow transplantation from HLA-matched unrelated donors for treatment of
      hematologic malignancies.
AB  - Less than 40% of the patients who could benefit from marrow transplantation have
      an HLA-matched relative who can serve as a donor. For this reason, several
      centers have explored marrow transplantation from other categories of donors.
      This retrospective study analyzes the results of marrow transplantation for 52
      patients receiving grafts from HLA-A,B,DR,Dw-phenotypically matched, MLC
      compatible, unrelated volunteer donors compared to a disease, disease-stage, and
      age-matched cohort of 104 patients transplanted from HLA-genotypically identical
      sibling donors. The patients transplanted from unrelated donors had an increased
      incidence of grade II-IV acute graft-versus-host disease compared to patients
      transplanted from related donors (79% vs. 36%, P much less than 0.001). However,
      the probability of relapse-free survival appears similar in the two groups (P =
      0.39 over all, with estimates of 41% vs. 46% at 1 year). We conclude from this
      preliminary data that marrow transplantation from HLA-matched unrelated donors
      should be considered in most, if not all, circumstances where transplantation
      from an HLA-matched sibling would be indicated if such a donor were available.

PMID- 1994542
TI  - The effects of donor-specific blood transfusion enhancement of rat renal
      allografts on cytotoxic activity and phenotypes of peripheral blood lymphocytes,
      splenocytes, and graft-infiltrating cells.
AB  - Donor-specific blood transfusion prolongs survival of fully allogeneic ACI (RT1a)
      renal grafts in PVG (RT1a) recipients from 6-8 days to greater than 100 days. To
      determine how DSBT alters effector cytotoxic cell responses, we tested freshly
      isolated peripheral blood lymphocytes, spleen cells, and graft infiltrating cells
      (GIC) from pairs of PVG recipients of ACI kidneys pretreated with DSBT or
      autologous blood transfusion (ABT) for cell-mediated lympholysis, antibody
      dependent cellular cytotoxicity (ADCC), and natural killer activity at the day of
      transplantation (day 0) and days 3 and 6 posttransplantation. PBL and GIC from
      the same pairs of animals were examined for their phenotypic profile (CD4, CD8,
      3.2.3 NK cell marker, IL-2 receptor). CML, ADCC, and NK activity were higher in
      PBL than splenocytes of GIC of both ABT and DSBT groups at all time points
      examined. CML activity of PBL at day 3 was significantly higher in DSBT vs. ABT
      recipients (P less than 0.01), while at day 6 both groups were equally elevated.
      Splenocytes demonstrated significantly lower CML activity in DSBT vs. ABT
      recipients at day 6 (P less than 0.05). CML activity of GIC eluted from ABT and
      DSBT kidneys was not detected at day 3, but was significantly elevated and
      equivalent in both groups at day 6. ADCC and NK activities of PBL did not differ
      between ABT and DSBT groups, and were negligible in splenocytes. GIC demonstrated
      higher NK activity in DSBT vs. ABT recipients at day 3 (P less than 0.05), while
      ADCC activity was not detectable at any time in either group. Phenotypic analysis
      of PBL and GIC at day 3 showed no significant differences between ABT and DSBT
      groups in the percentage of CD4 or CD8 cells. However, in both ABT and DSBT
      groups the ratio of CD4:CD8 cells was markedly lower in GIC than PBL. By day 6,
      PBL from both ABT and DSBT groups showed equivalent and significant decreases in
      CD4+ cells and increases in CD8+ and 3.2.3+ (NK) cells. The percentage of IL-2R+
      cells remained low (less than 5%) in both groups at day 3. In contrast, at day 6
      there was a significant increase in IL-2R+ (and to a lesser extent CD4+) GIC in
      ABT- but not DSBT-treated recipients, while CD8+ cells were significantly
      increased in both groups.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1994543
TI  - Evidence that epidermal alloantigen Epa-1 is an immunogen for murine heart as
      well as skin allograft rejection.
AB  - Epa-1 is a non-H-2 mouse alloantigen defined by MHC-restricted, CD8+ cytotoxic T
      cells. In vitro it is a strong determinant for the lysis of epidermal cells,
      fibroblasts, and macrophages but not lymphocytes, and in vivo it functions as a
      target for skin allograft rejection and cutaneous graft-versus-host reactions.
      Genetically, Epa-1 appears to be the nonpolymorphic manifestation of a loss
      mutation. The establishment of C3H.Epa-1 (Epa), an Epa-1+ congenic strain on the
      Epa-1- C3H/HeJ (C3H) inbred strain background, facilitated the investigation of
      the role of Epa-1 in skin and heart allograft rejection. C3H females and males
      rejected first-set Epa skin grafts with median survival times (MSTs) of 20 and 30
      days, respectively. However, there was a strong factor of immunization, because
      all second-set skin allografts were rejected by hosts of both sexes within 10
      days. In contrast, all Epa hosts of both sexes permanently accepted C3H skin
      allografts, consistent with Epa-1 arising from a loss mutation. C3H hosts of both
      sexes rejected primarily vascularized first-set Epa heart allografts in similar
      tempo to first-set Epa skin allografts, with MSTs of about 30 days. However, in
      contrast to the accelerated rejection of skin allografts, sensitized C3H hosts
      rejected Epa heart allografts in chronic fashion, with some transplants showing
      very prolonged survival. Thus, Epa-1 is a relatively strong determinant of skin
      allograft rejection but a weaker determinant of heart allograft rejection.

PMID- 1994544
TI  - IgM and IgG alloantibody production by splenocytes and deposition in rat renal
      allografts are decreased by donor-specific blood transfusion.
AB  - Untreated PVG (RT1c) rats reject ACI (RT1a) renal grafts in 6-8 days. Autologous
      (PVG) blood transfusions (ABT) do not alter ACI allograft rejection, but donor
      specific blood transfusions (DSBT) 7 or 11 days prior to transplantation usually
      results in indefinite graft survival. We have reported previously that DSBT is
      associated with the development of antiidiotypic antibody and reduced circulating
      cytotoxic alloantibodies in this model. To further define the effects of DSBT on
      the alloantibody responses to renal allografts, we examined PVG rats that
      received DSBT or ABT prior to ACI renal transplantation. Antibody production by
      cells in the spleen was investigated by tissue culture techniques; circulating
      antibody titers were measured by antibody binding to target ACI lymphoblasts with
      flow cytometry; and antibodies bound to the ACI allograft were recovered by
      hypertonic acid elution and quantitated by flow cytometry and ELISA. Seven days
      after DSBT alone, circulating IgM alloantibodies to ACI reached peak titers.
      After renal allografting, serum IgM alloantibody titers decreased in DSBT
      pretreated rats and little IgG could be detected. In contrast, renal allografts
      in ABT-pretreated rats elicited high titers of IgM and moderate titers of IgG in
      the circulation by 5-7 days posttransplantation. Spleens harvested one week
      posttransplantation from ABT-pretreated rats produced high titers (16-32) of IgM
      and IgG antibodies to ACI antigens, but no such antibody production was detected
      in spleens cultured from DSBT-pretreated rats. In addition, 4-32-fold more IgM
      and IgG was eluted from kidneys removed 6-7 days after grafting to ABT-treated
      rats than from allografts in DSBT-treated rats. IgG2a was the predominant
      subclass of IgG that bound to target ACI cells. No IgA was detected in graft
      eluates from any rat. Polyacrylamide gel electrophoresis demonstrated that the
      eluates contained predominantly IgM and IgG without significant contamination by
      other serum proteins. These data suggest that DSBT decreases the levels of IgM
      and IgG normally produced in the spleen and deposited in the graft following
      renal transplantation. Because IgM fixes complement and IgG (especially IgG2a)
      triggers ADCC, the reduced deposition of IgM and IgG in the graft may be of
      particular importance in DSBT enhancement.

PMID- 1994545
TI  - Stimulus-specific 1,25(OH)2D3 modulation of TNF and IL-1-beta gene expression in
      human peripheral blood mononuclear cells and monocytoid cell lines.
AB  - It is known that 1,25(OH)2D3 inhibits IL-2, IFN-gamma, and GM-CSF mRNA
      accumulation in activated T cells. While 1,25(OH)2D3 enhances macrophage
      competence, its effect on cytokine gene expression in monocytes is less well
      defined. Using Northern blot analysis, we examined the effect of 1,25(OH)2D3
      pretreatment on IL-1 beta and TNF gene expression in LPS- and PHA-stimulated
      human PBMNC and several human myeloid cell lines (U937 and THP1). In PBMNC,
      preincubation had no effect on the steady-state level of LPS-induced TNF or IL-1
      beta mRNA. When PHA was used to stimulate pretreated PBMNC, a 60-80% inhibition
      of TNF mRNA levels was observed. There was no effect on IL-1 beta mRNA. In U937
      cells, 1,25(OH)2D3 preincubation resulted in a 4-fold increase in the level of
      TNF and IL-1 beta mRNA levels. Pretreatment had no effect on TNF or IL-1 beta
      gene expression in THP1 cells. The observation that PHA-induced TNF gene
      expression is modulated by 1,25(OH)2D3 is novel. Possible mechanisms by which
      1,25(OH)2D3 preincubation may influence mitogen-specific inducible cytokine gene
      expression in different cell types are discussed.

PMID- 1994546
TI  - Effects of chronic cyclosporine administration on renal blood flow and intrarenal
      blood flow distribution.
AB  - Cyclosporine-induced decreases in renal blood flow (RBF) and glomerular function
      are well documented. Glomerular filtration and tubular function may be affected
      by changes in both total renal blood flow and cortical blood flow distribution
      (CBFD). The effect of CsA on RBF, CBFD, glomerular filtration rate, and tubular
      function was studied in conscious ewes receiving a mean CsA dose of 30 mg/kg/day
      for 28 days with mean CsA trough levels of 344 +/- 45 ng/ml. RBF and CBFD were
      determined by the injection of 15 microns radioactive microspheres before and
      after one month of treatment with CsA or its vehicle, olive oil. RBF decreased by
      24% from 7.65 +/- 0.87 to 5.79 +/- 0.42 ml/min/g of kidney in CsA-treated ewes (P
      = 0.014), while no decrease was noted in the control group (7.92 +/- 1.10 vs.
      7.62 +/- 0.71). Intracortical blood flow decreased in proportion to the fall in
      total renal blood flow--thus CsA treatment did not change the cortical
      distribution of flow. There was a 25% decrease in GFR, as determined by inulin
      clearance, in the CsA-treated group (80 +/- 6 vs. 62 +/- 3 ml/min; P = 0.027)
      while there was a nonsignificant increase in control animals (62 +/- 11 vs. 92 +/
      7 ml/min). There was no evidence of tubular dysfunction in either group. There
      were also no changes in urinary excretion rates of prostaglandins PGE2, 6-keto
      PGF1 alpha or thromboxane B2, nor were there changes in plasma renin activity.
      CsA induced decreases in RBF occur red without redistribution of cortical blood
      flow, indicating that altered cortical distribution of blood flow is not
      responsible for the changes in GFR or tubular function that have been reported.
      The changes in renal blood flow and glomerular filtration rate are independent of
      changes in renal prostaglandin production, and are likely not associated with
      altered plasma renin activity.

PMID- 1994548
TI  - Expression of the protease gene HF as a marker in rejecting allogeneic murine
      heart transplants.
AB  - Phenotypic characterization of the inflammatory infiltrate often provides very
      little information about the fate of a transplant. Therefore we decided to look
      for functional markers, characteristic for activated effector cells involved in
      the rejection of primarily vascularized MHC-mismatched heart transplants in mice.
      Infiltrating cells in the interstitium of eventually rejected allogeneic heart
      transplants were found to express the gene for the serine esterase HF (granzyme
      A) in high numbers already on day 2 following transplantation, whereas HF mRNA
      positive cells were absent, or only rarely found, in syngeneic nonrejecting
      transplants throughout the entire observation period of 10 days after
      transplantation. These findings could also become of importance for the
      prediction of the outcome of organ transplants in humans.

PMID- 1994547
TI  - Failure of prolyl-peptidyl isomerase to mediate cyclosporine suppression of
      intracellular activation signal generation.
AB  - Cyclosporine blocks the generation of a cytoplasmic activation protein, activator
      of DNA replication (ADR). The recent demonstration that cyclophilin is a CsA
      sensitive prolyl-peptidyl-isomerase (PPIase), has prompted speculation that CsA
      immunosuppression is mediated by PPIase interaction with activation signals like
      ADR. We report that PPIase converts ADR from an inactive to an active form, but
      the interaction is resistant to CsA. ADR is a sensitive marker of CsA
      immunosuppression. ADR, extracted from the cytoplasm of PBLs stimulated with PHA,
      is not detectable in the cytoplasm of resting cells. ADR is quantitated by
      measuring uptake of 3H/thymidine triphosphate (3H/TPP) into isolated nuclei as a
      measure of DNA synthesis. The CsA-induced reduction of ADR content mirrored CsA
      induced proliferative inhibition in intact cells. CsA concentrations of 1.5, 3,
      or 4.5 mM reduced T cell proliferation by 26%, 47%, and 58%, and ADR content by
      32%, 45%, and 53%, respectively. The ability of PPIase to catalyze the transition
      of ADR between active and inactive forms was determined by measuring changes in
      DNA synthesis when 1 microgram/ml PPIase was added to (1) isolated nuclei, (2)
      nuclei plus ADR, and (3) nuclei plus the cytoplasmic fraction from resting cells.
      DNA synthesis in isolated nuclei (899 +/- 45 cpm) was unchanged by PPIase (1009
      +/- 221 cpm). Addition of PPIase to ADR from activated cells marginally reduced
      ADR's capacity to trigger 3HTTP incorporation into isolated nuclei (ADR, 4113 +/-
      106 cpm; PPIase-treated ADR, 3198 +/- 453 cpm), showing that PPIase cannot reduce
      ADR activity. However, treatment of resting cell cytoplasm with PPIase increased
      ADR activity 5-fold (899 +/- 46 vs. 5035 +/- 75 cpm). Addition of 1.5 or 3 mM CsA
      to resting cytoplasm, primed with PPIase (5035 +/- 75 cpm), resulted in 3HTPP
      incorporation of 6575 +/- 152 and 5076 +/- 168 cpm, respectively. Thus, PPIase
      activation of ADR is CsA-resistant. Furthermore, PPIase could not reverse CsA
      induced inhibition of ADR. CsA (3 mM) treatment of PHA-stimulated cells rendered
      proliferation by 30% and ADR by 35%. ADR isolated from cells treated with CsA
      (9110 +/- 750 cpm) was not increased by treatment with PPIase (9185 +/- 449 cpm).
      These findings suggest that PPIase converts ADR from an inactive to an active
      form. However, the mechanism of CsA inhibition of ADR is neither mediated nor
      overridden by PPIase.

PMID- 1994549
TI  - Characterization of the in vitro sensitivity of human lymphoid and hematopoietic
      progenitors to L-leucyl-L-leucine methyl ester.
AB  - L-leucyl-L-leucine methyl ester (LLME) is a lysosomotropic agent that in
      microMolar concentrations has been found to be selectively toxic to human and
      murine precursor and effector cytotoxic cells, irrespective of their surface
      membrane phenotype. We describe a new method of synthesis of LLME and evaluate
      the effects of this preparation on human lymphoid and hematopoietic progenitor
      cells. The new method of synthesis did not change the previously characterized
      activities of LLME. Consistent with previous observations, NK effectors, LAK
      precursors and effectors, and allospecific CTL (aCTL) effectors were completely
      ablated by treatment with 50-250 microM LLME, while the activities of helper T
      cells and B cells were preserved after treatments of up to 1000 microM LLME. The
      effects of LLME treatment on human marrow-derived erythroid, myeloid, and
      monocyte progenitors have not been previously described. We found that the growth
      of each of these committed precursors was reduced or eliminated following
      treatment with 100-250 microM LLME. Admixture of LLME-treated marrow with marrow
      depleted of T cells and other mature cellular elements resulted in increased
      growth of myeloid and erythroid colonies suggesting that cells that could provide
      colony-enhancing activities were preserved. In contrast to previous studies in
      humans, we found a minority of individuals to have aCTL precursors that were
      partially resistant to LLME. PBL from 10 of 15 individuals tested showed nearly
      complete ablation of aCTL precursors following treatment with 375 microM LLME.
      The remaining 5 individuals demonstrated significant aCTL precursor activity
      after identical treatment. The resistance to LLME was restricted to aCTL
      precursors, and neither increasing the dose of LLME nor prolonging the time of
      treatment completely overcame the resistance. The pattern of susceptibility
      (sensitive versus resistant) was found to be independent of the degree or type of
      HLA disparity between responder and stimulator. LLME-treated cultures with and
      without CTL activity contained a predominance of CD4+ T cells. However, in the
      subjects tested LLME-resistant aCTL was shown to be CD8+. In vitro priming of
      aCTL precursors from sensitive individuals did not consistently result in the
      development of resistance to LLME. These data indicate that further studies are
      needed to evaluate the effects of LLME on human stem cells and to determine the
      potential role of resistant aCTL precursors in GvHD prior to application of this
      technique as a form of selective T cell depletion in humans.

PMID- 1994550
TI  - Evidence that the fate of class II-disparate corneal grafts is determined by the
      timing of class II expression.
AB  - While the immune privilege nature of the eye affords significant protection to
      corneal grafts, immunologic rejection is the leading cause of graft failure.
      Class II antigens are normally absent or expressed at very low levels in normal
      cornea. The role that class II antigens play in causing graft rejection is
      particularly interesting. Class II molecules are present on many cells of the
      immune system, and therefore are important in modulating and mediating immune
      reactions. The absence of class II bearing cells in the cornea leads to the
      interesting issue of whether or not those antigens can induce immune rejection of
      a corneal graft. In the current study we have made use of a pair of congenic rat
      strains that differ only at class II loci to determine the impact of these
      antigens on corneal graft survival. Central corneal grafts were not rejected.
      Recipients preimmunized with skin grafts rejected 100% of the class II disparate
      corneas with a median survival time (MST) of 15.5 days. When class II disparate
      Langerhans-cell-containing (LC+) corneas were grafted, the corneas were not
      rejected, but they immunized the recipients as evidenced by the rejection of a
      second corneal graft on the contralateral eye. Immunofluorescent stains
      demonstrated transient expression of class II antigens on graft epithelium after
      transplantation. This temporary appearance of class II provides a target for
      rejection in the preimmunized animals but is of insufficient duration to both
      prime naive animals and provide a target for antigraft effectors.

PMID- 1994551
TI  - Flow cytometric crossmatching and long-term kidney allograft survival in donor
      specific transfusion patients.

PMID- 1994552
TI  - [Reappraisal of Niels Stensen's "new muscular structure" from 1667].

PMID- 1994553
TI  - [Extracorporeal shockwave crushing of gallstones. Preliminary report].
AB  - Extracorporeal shock wave lithotripsy (ESWL) was used for treatment of
      symptomatic x-ray negative stones in 23 patients. The number of ESWL sessions per
      patient was 1.8 (range 1-4). In 18 patients (78%), adequate fragmentation was
      seen comparable to results obtained elsewhere. Oral bile acid therapy was used
      after ESWL in the 18 patients mentioned and the mean follow-up period was five
      months (range 3-8 months). Four patients had by now passed all stones while 12
      patients still had remaining stone fragments and one patient a gallstone. After
      ESWL, one patient was and one patient a gallstone. After ESWL, one patient was
      referred for cholecystectomy at his own request. Of the remaining five patients,
      cholecystectomy was performed in two and was scheduled for in three.
      Complications after ESWL were seen in two patients who developed acute
      pancreatitis. Thus, our preliminary experience shows that ESWL resulted in
      fragmentation and passing of gallbladder stones, but not without complications.
      Like the gallstone groups in Lyon, Montreal and Munich we are convinced that ESWL
      should be performed in accordance with prospectively designed protocols in order
      to establish optimal planning of indications and strategies for future treatment.

PMID- 1994554
TI  - [The new ambulatory non-invasive 24-hour blood pressure monitoring system, Takeda
      Medical TM 2420. Reliability and practical experiences].
AB  - Takeda TM 2420 is an automatic ambulant device for measuring blood pressure which
      functions by auscultation of the Korokoff sounds. During static conditions, the
      apparatus was investigated by means of a double stetoscope and a connecting
      branch with the Hawksley random zero manometer. Where 69 persons were concerned
      (ages 13-89 years, systolic blood pressures 85-212 mmHg, diastolic blood pressure
      44-110 mmHg) a difference in the systolic blood pressure of 1.5 +/- 9.2 mm Hg
      were found (average +/- standard deviation) and where the diastolic blood
      pressure was concerned 2.8 +/- 6.3 mm Hg. Statistical comparison with the
      Hawksley manometer on the contralateral arm in 51 volunteers produced
      corresponding results. In 24-hour monitoring of 80 persons, useful results were
      obtained in 74. The proportion of erroneous measurements was acceptable but the
      apparatus was unsuitable for exercise testing on an ergometer bicycle. The
      quality of the cuff, the connecting tubing, the carrying strap and computer
      programmel should be improved but the apparatus was otherwise found to be useful
      for daily clinical use.

PMID- 1994555
TI  - [Assessment of micturition cystourethrography. Intra- and inter-observer
      variation].
AB  - The reliability of any method of investigation depends upon the accuracy and
      reproducibility of the results of the investigation. The accuracy of voiding
      cystoureterography (VCU) which is greatly dependent on the radiographic
      assessment cannot be assessed because no standard answers exist. The reliability
      of the method may be assessed in the form of intra- and inter-observer
      variations. VCU investigations from 24 women with incontinence were assessed by
      two independent radiologists. Fifteen of the radiological examinations had
      previously been described by one of the radiologists so that intra-observer
      variation could be assessed by these. Inter-observer variation was 70% (95%
      confidence limits 51-89%), calculated from the diagnoses anterior and posterior
      suspension defects, combined defects and normal conditions. The corresponding
      intra-observer variation was 53% (95% confidence limits 27-78%). The radiographic
      criteria for subdivision of suspension defects into anterior and posterior
      defects are, theoretically, very simple but appear to be difficult to attain in
      practice. The indications for employing a form of examination where assessment of
      the result of examination is so obscure should be very weighty.

PMID- 1994556
TI  - [Retroperitoneal complications after lumbar disk prolapse surgery].
AB  - Injury to retroperitoneal vascular structures secondary to lumbar disc surgery is
      a rare but serious complication. In some cases early recognition and surgical
      intervention is of vital importance. Vascular injuries may be classified in in
      the following manner. 1. Laceration of one artery or a vein only. 2. Laceration
      of a artery and a vein leading to formation of arteriovenous fistula. 3. False
      aneurysm. Based on a review of the literature and three case reports, the anatomy
      is reviewed. The diagnosis, clinical pictures and the vascular reconstruction are
      discussed.

PMID- 1994557
TI  - [Shark liver oil (alkoxyglycerol) and cancer treatment].
AB  - Alkoxyglycerol derived from shark liver oil is marketed in Denmark and mentioned
      in popular articles as a supplementary agent in the treatment of cancer. A
      questionnaire investigation carried out in the Department of Oncology and
      Haematology in Odense Hospital revealed that approximately 1/3 of the patients in
      active neoplastic therapy employed shark liver oil preparations. The clinical
      investigations of alkoxyglycerol were all carried out on patients with cancer of
      the uterine cervix. All of the investigations were carried out by the same
      Swedish research group. Only a minority of the experimental material was blinded.
      No documentation was found for inhibited tumour growth or reduced mortality
      resulting from treatment with alkoxyglycerol. The number of cases of irradiation
      damage were found to be fewer in the groups treated with alkoxyglycerol, but the
      difference may be partially explained by different subdivision into stages.
      Alkoxyglycerol results in increase in the leukocyte and thrombocyte counts while
      higher or lower doses have, apparently, the opposite effect. The available
      literature concerning the clinical effect of alkoxyglycerol is limited and
      unsystematic and does not support the employment of alkocyglycerol in the
      treatment of cancer.

PMID- 1994558
TI  - [Lumbar regional analgesia in patients during antithrombotic treatment.
      Procedures used at the Danish anesthesiologic departments illustrated by a
      questionnaire study].
AB  - The attitudes of Danish anaesthetists to employment of lumbar epidural analgesia
      (EA) or spinal analgesia (SA) in patients receiving perioperative antithrombotic
      therapy was assessed by a questionnaire investigation. EA and SA were absolute or
      relative contraindications in patients receiving low-dose heparin therapy in 38%
      and 24% of the departments. The same figures for patients receiving dextran or
      acetylsalicylic acid therapy were 3-8%. The limiting value for the P-coagulation
      factors II, VII and X for employing EA and SA varied considerably in the
      departments questioned. EA and SA were, however, contraindicated in patients
      receiving regular anticoagulation in the majority of departments. On a national
      basis, only two confirmed cases of symptom-producing haemorrhage in the spinal
      canal which could be attributed to thrombosis prophylaxis after SA/EA have been
      recognized. Both of these developed after regular anticoagulation therapy. The
      authors do not find any basis for warning against use of EA/SA in patients
      receiving subcutaneous heparin therapy, dextran or acetyl salicylic acid, unless
      another predisposition to haemorrhage is present.

PMID- 1994559
TI  - [Clinical continuing education of younger physicians. A pedagogic trial with
      postgraduate clinical training using the clinical decision process].
AB  - The aim of this study was to improve the clinical training of the staff of a
      department of internal medicine. A total of 16 clinical pathological conferences
      with patient demonstrations were given. The doctor in charge of the conference
      motivated his choice of patient and made a critical review of the clinical
      decision process according to a 16 item check list. The median time used for
      planning of the presentation was five hours, range 2.5-8 hours. Sixteen of the
      participants (94%) found the training programme of very high or high quality
      while 1 (6%) found it less good. Fifteen (88%) of the doctors indicated higher
      clinical skill after than before the conferences (p less than 0.01). The
      registrars revealed a significantly better improvement of their clinical skills
      than did the senior registrars and consultants (p less than 0.05). The median
      educational value of the items of the check list was stated to be 1.3 (0-2).
      Statement of the probability of the final diagnosis of the patient, value
      judgement in clinical decisions and costs of diagnostic examinations were
      considered of highest educational value, 1.5-1.6. Postgraduate clinical
      pathological conferences with patient demonstrations including systematic reviews
      of the clinical decision process are valuable in the clinical training of
      doctors.

PMID- 1994560
TI  - [The terminal complement complex (TCC)--a mediator in the development of disease
      in man?].
AB  - Activation of the terminal complement pathway leads to the formation of the
      terminal complement complexes (TCC). TCC exists in one active membrane form, C5b
      9 and in one inactive fluid phase form, SC5b-9. The paper explores the structure
      and regulatory mechanisms of TCC. In addition, methods of detecting TCC in tissue
      and in biological fluids, guidelines for sampling and the importance of TCC as an
      inflammatory mediator in human disease are discussed.

PMID- 1994561
TI  - [Bladder tumors in West Lolland. A case-control study of occupational exposure in
      a risk region].
AB  - The Danish Cancer Register recorded a significant excess incidence of bladder
      tumours among men in West Lolland during the period 1970 and 1979. No
      corresponding excess incidence of cancer of the lung was recorded. This might
      suggest that causes other than increased prevalence of smokers explain the
      recorded findings. A case-control investigation was carried out to illustrate
      possible occupational causal factors with the aid of the Cancer Register database
      concerning cancer and occupation which is based on linking of the Cancer Register
      with the Supplementary Pension Fund (additional pensions supplementary pension
      fund awarded via the Labour Market.) Increased risks of bladder tumours were
      demonstrated in several occupations which are recognized as involving a risk for
      this disease. A significantly increased risk was demonstrated in the transport
      occupation. No evidence was found to suggest that the peculiar occupational
      structure of the region could explain the excess risk registered.

PMID- 1994562
TI  - [Standardized prothrombin time determinations and optimal anticoagulant therapy].
AB  - WHO and other international organizations have recommended the introduction of a
      standardized prothrombin time determination. This would allow a universal scale
      for the intensity of oral anticoagulation therapy to be used. A prerequisite is
      the use of thromboplastin, calibrated against the international reference
      thromboplastin, standardized methodology etc. This permits every prothrombin time
      determination to be expressed as International Normalized Ratio (INR). The
      introduction of INR facilitates the implementation of optimal oral
      anticoagulation as defined by larged international studies.

PMID- 1994564
TI  - [Idiopathic aortoduodenal fistula].
AB  - A case of primary aortoduodenal fistula of unknown origin in a 72 year old female
      is presented. The fistula was successfully treated by excision from the duodenum
      and direct suture of the aortic wall.

PMID- 1994563
TI  - [Toxic reaction to bupivacaine].
AB  - A case of toxic reaction to bupivacaine which was administered epidurally to a
      pregnant woman is presented. The test dosage and the aspiration test are
      discussed. The value of fractionated administration of bupivacaine is emphasized.

PMID- 1994565
TI  - [Early Greenlandic medical reports and later Greenlandic population statistics].

PMID- 1994566
TI  - [Moral choice and occupational health services].

PMID- 1994568
TI  - [Sexual habits among women in Manitsoq/Sukkertoppen].

PMID- 1994567
TI  - [Ubiquinone--supplementary remarks on therapeutic possibilities].

PMID- 1994569
TI  - Antiviral effects of xanthate D609 on the human respiratory syncytial virus
      growth cycle.
AB  - The antiviral compound tricyclo-decan-9-yl-xanthogenate (D609) inhibits
      respiratory syncytial (RS) virus growth in human epithelial (Hep 2) cells. D609
      treatment resulted in a decrease in the accumulation of viral proteins, in the
      phosphorylation of the viral phosphoprotein, and in the amount of extracellular
      antigens and infectious particles. The relative accumulation of viral proteins
      was also unbalanced, however no differences were found in the amount of viral RNA
      with plus or minus polarity. In addition nucleocapsids formation was not
      inhibited. These observations suggested that this antiviral compound affects the
      relative proportion of viral proteins and the phosphorylation of P protein. Both
      features appear to be important in RS virus morphogenesis.

PMID- 1994570
TI  - In vivo complementation of infectious transcripts from mutant tobacco mosaic
      virus cDNAs in transgenic plants.
AB  - A full-length cDNA clone of the U1 (common) strain of tobacco mosaic virus (TMV)
      was constructed, and highly infectious transcripts were produced in vitro using
      bacteriophage T7 RNA polymerase. Frameshift mutations designed to cause premature
      termination of translation were introduced into either the 30-kDa movement
      protein (MP) gene or the coat protein (CP) gene. The MP-frameshift mutant was
      unable to locally or systemically infect inoculated tobacco plants. However,
      inoculation of transgenic tobacco plants that expressed a wild-type TMV MP gene
      resulted in both local and systemic viral infection. The CP-frameshift mutant,
      although unable to move systemically in nontransformed tobacco, exhibited
      systemic movement in transgenic plants that expressed a wild-type TMV CP gene.
      Transgenic tobacco plants that expressed the appropriate wild-type TMV gene were
      thus able to complement, in trans, mutant viruses lacking a functional MP or CP
      gene.

PMID- 1994572
TI  - A novel HIV-1 isolate containing alterations affecting the NF-kappa B element.
AB  - Three molecular clones of HIV-1, derived from a single isolate (AL1), exhibited
      distinct replicative and cytopathic properties during propagation in a human T
      cell line. The phenotypic differences observed were attributable, in large part,
      to changes affecting the viral LTR. Nucleotide sequence and PCR analyses
      demonstrated the presence of novel duplications or deletions involving the NF
      kappa B motif. These changes in the enhancer element were identified in the
      original AL1 virus stock. Subcloning of the variant NF-kappa B segments into LTR
      driven CAT expression vectors confirmed a correlation between promoter activity
      and replicative/cytopathic capacity.

PMID- 1994571
TI  - Nucleotide sequence analysis of the bovine respiratory syncytial virus fusion
      protein mRNA and expression from a recombinant vaccinia virus.
AB  - Bovine respiratory syncytial (BRS) virus is an important cause of serious
      respiratory illness in calves. The disease caused in calves is similar to that
      caused by human respiratory syncytial (HRS) virus in children. The two viruses,
      however, have distinct host ranges and the attachment glycoproteins, G, have no
      antigenic cross-reactivity. The fusion glycoproteins, F, of the HRS and BRS
      viruses, however, have some antigenic cross-reactivity. To further compare the
      BRS virus and HRS virus fusion proteins, we determined the nucleotide sequence of
      cDNA clones to the BRS virus F protein mRNA, deduced the amino acid sequence, and
      compared these sequences with the HRS virus F protein sequences. The BRS virus F
      mRNA was 1899 nucleotides in length and had a single major open reading frame
      which could code for a polypeptide of 574 amino acids with an estimated molecular
      weight of 63.8 kDa. Structural features predicted from the amino acid sequence
      included an NH2-terminal signal sequence (residues 1-26), a site for proteolytic
      cleavage (residues 131-136) to generate the disulfide-linked F1 and F2 subunits,
      and a hydrophobic transmembrane anchor sequence (residues 522-549). The nucleic
      acid identity between the BRS virus and the HRS virus F mRNA sequences was 71.5%.
      The predicted BRS virus F protein shared 80.5% overall amino acid identity with
      the HRS virus F protein with 89% identity in the F1 polypeptide but only 68%
      identity in the F2 polypeptide. The position and number of the cysteine residues
      in the F1 and F2 polypeptides were conserved among all F proteins. However, BRS
      virus F protein had only three potential N-linked carbohydrate acceptor sites in
      comparison to four or five for the HRS viruses. A difference in the extent of
      glycosylation between the BRS and HRS virus F2 polypeptides was shown to be
      responsible for differences observed in the electrophoretic mobility of these
      proteins. A cDNA containing the complete open reading frame of the BRS virus F
      mRNA was inserted into the thymidine kinase gene of vaccinia virus and following
      homologous recombination, a recombinant virus containing the BRS virus F gene was
      isolated. The BRS virus F protein was expressed in recombinant virus infected
      cells as demonstrated by immunoprecipitation and was transported to and expressed
      on the surface of infected cells as shown by indirect immunofluorescence.

PMID- 1994573
TI  - Regulation of plaque size and host range by a vaccinia virus gene related to
      complement system proteins.
AB  - A vaccinia virus variant, LC16m8, and its parental Lister (Elstree) strain (LO)
      were employed to identify the viral gene(s) responsible for plaque size and host
      range: the large-plaque-forming LO strain but not the small-plaque-forming LC16m8
      strain can actively proliferate in Vero (YTV) cells. Previously, we suggested
      that some particular gene(s) present in the HindIII D fragment of LO DNA was
      responsible for these biological activities. In the present experiment, the
      mapping of the putative gene was done by introducing various subfragments of the
      HindIII D fragment of LO DNA into the gene of LC16m8 strain and screening of the
      resultant virus variants for the capability of forming large plaques or of
      proliferating well in Vero cells. The results indicated that an open reading
      frame (called ps/hr gene) in LO HindIII D fragment was responsible for either
      plaque size or host range. This gene encoded a polypeptide of 317 amino acids
      related to the regulators of complement activation (RCA) gene family of mammals.
      Thus, the present genetic analysis provided direct evidence for a previously
      unrecognized function of RCA-related proteins encoded by the virus.

PMID- 1994574
TI  - De novo generation of defective interfering RNAs of tomato bushy stunt virus by
      high multiplicity passage.
AB  - Defective interfering (DI) RNAs were generated de novo in each of 12 independent
      isolates of tomato bushy stunt virus (TBSV) upon serial passage at high
      multiplicities of infection (m.o.i.) in plants, but not in any of 4 additional
      isolates after 11 serial passages at low m.o.i. The DI RNAs were detected in RNA
      isolated from virus particles and in 2.3 M LiCl-soluble RNA fractions isolated
      from inoculated leaves. Symptom attenuation leading to persistent infections was
      closely correlated with the passage in which DIs first developed. Comparisons of
      nucleotide sequences of 10 cDNA clones from 2 DI RNA populations and with a
      previously characterized TBSV DI RNA revealed the same four regions of sequence
      from the TBSV genome were strictly conserved in each of the DI RNAs: the virus 5'
      leader sequence of 168 bases; a region of approximately 200-250 bases from the
      viral polymerase gene; approximately 70 bases from the 3' terminus of the viral
      p19 and p22 genes; and approximately 130 bases from the 3' terminal noncoding
      region. Conservation of the sequence motif present in all of the DIs suggests
      that there might be a common mechanism of DI formation as well as selection
      pressure to maintain sequences essential for replication and encapsidation.

PMID- 1994575
TI  - Protein p22 of African swine fever virus: an early structural protein that is
      incorporated into the membrane of infected cells.
AB  - The open reading frame K'177, located at the left end of the African swine fever
      virus genome, codes for an early induced structural protein of 22,000 Da (p22),
      which is released from the viral particle by the nonionic detergent n-octyl-beta
      D-glucopyranoside under conditions that solubilize external viral structural
      proteins. The predicted amino acid sequence of the protein contains a hydrophobic
      region at its N-terminus with characteristics of a signal peptide and, at early
      times after virus infection of Vero cells, the protein can be detected in the
      cell membrane by immunolabeling.

PMID- 1994576
TI  - Genetic and molecular biological characterization of a vaccinia virus temperature
      sensitive complementation group affecting a virion component.
AB  - The gene affected by five previously isolated temperature-sensitive (ts) mutants
      (ts 10, ts 18, ts 38, ts 39, ts 44) of vaccinia virus strain WR constituting a
      single "normal" complementation group has been characterized. Marker rescue and
      DNA sequence analysis show that the five members of the complementation group map
      in an open reading frame, ORF 18R, which spans the HindIII I-G junction and has
      the capacity to encode a 77.6-kDa protein. The nucleotide sequence change
      responsible for temperature sensitivity in each of the five mutants was
      determined. Two of the mutants, ts 38 and ts 44, have the identical nucleotide
      change and may therefore be sisters. Northern blot analysis demonstrates that ORF
      18R is transcribed at both early and late times during infection. Two distinct
      early transcripts have been observed which are 5' coterminal and which contain a
      518 nucleotide 5' untranslated region. The long early transcript spans the entire
      18R gene while the 3' end of the shorter early transcript maps to an early
      transcription termination signal contained within the 18R coding sequence. The 5'
      ends of the late transcripts have been mapped to a family of AUG proximal sites
      using both S1 nuclease and primer extension analysis. Primer extension analysis
      also identifies additional late 5' ends which map between nucleotides -500 and 
      1000 relative to the ORF 18R AUG.

PMID- 1994577
TI  - Phenotypic characterization of a vaccinia virus temperature-sensitive
      complementation group affecting a virion component.
AB  - Genetic and biochemical evidence is presented which shows that the product of the
      vaccinia virus gene 18R is a virion protein. Western blot analysis of virion
      proteins using anti-18R serum detects a 78,000-Da protein, localized in the virus
      core. Of five ts mutants which map to gene 18R, two mutants, ts 10 and ts 44,
      possess thermolabile virions. Temperature shifts performed during single-step
      growth of ts 44 suggest that precursors required for virion maturation accumulate
      during nonpermissive infections with ORF 18R mutants and that protein synthesis
      is required for recovery from nonpermissive condition.

PMID- 1994578
TI  - Altered host range of HIV-1 after passage through various human cell types.
AB  - HIV-1 strains, including a molecularly cloned isolate, that had been passaged
      through different cell types adapted to faster growth in the same cell type and
      displayed a different host cell tropism. The only change in viral proteins
      revealed by immunoblot analyses was the molecular size of the envelope
      glycoprotein gp120 that varied for viruses recovered from the different infected
      cells. The alteration in size was most likely the result of modification of
      gp120. Host range differences were also observed for a molecularly cloned HIV-1
      strain when passed through the peripheral white blood cells from different
      individuals. Thus, this phenomenon could have clinical relevance in HIV
      pathogenesis.

PMID- 1994579
TI  - Host range and symptoms are determined by specific domains of the maize streak
      virus genome.
AB  - We have cloned two distinct symptomatic variants of the geminivirus streak virus
      from maize plants infected with the Nigerian strain (MSV-N). Following
      "agroinoculation" to maize plants MSV-Nm produces narrow, mildly chlorotic
      discontinuous streaks, whereas MSV-Ns-infected tissue has wide, severely
      chlorotic streaks. Symptom appearance is delayed following MSV-Nm inoculation.
      MSV-Nm has a narrow host range within the Gramineae comprising a fraction of that
      of the wide host range isolate MSV-Ns. The two isolates are highly homologous and
      have identical restriction enzyme maps. In order to localize the determinants of
      pathogenicity we constructed, in vitro, hybrid genomes by restriction enzyme
      fragment exchange. The determinants of host range, severity of chlorosis, streak
      length, and timing of symptom appearance map to a fragment which includes the
      large intergenic region and the 5' terminus of the complementary sense C1 gene.
      Streak width is determined by the virion-sense portion of the genome, which is
      consistent with the observation that the virion-sense gene products (V1 and V2)
      are required for spread of the virus.

PMID- 1994580
TI  - The metabolism of host RNAs in cells infected by an adenovirus E4 mutant.
AB  - Mutants of adenovirus type 5 (Ad5) that lack early region 4 (E4) are defective in
      the expression of viral late genes. E4 mutants exhibit dramatically reduced
      levels of both cytoplasmic and nuclear viral late RNAs compared to wild-type
      virus, due principally to reduced stability of unprocessed viral late RNA in the
      nucleus of mutant-infected cells. To determine whether E4 products also affect
      the metabolism of host RNAs in infected cells, steady-state levels of beta-actin
      RNA and triose phosphate isomerase (TPI) RNA were measured in the cytoplasms and
      nuclei of HeLa cells infected by either wild-type Ad5 or the E4 deletion mutant
      H5dl1004, and were compared to levels in uninfected HeLa cells. S1 nuclease
      analyses revealed only slight reductions in beta-actin mRNA levels in the
      cytoplasm and in levels of spliced and unspliced beta-actin RNA in the nucleus of
      cells infected by either Ad5 or H5dl1004. RNase protection analyses showed that
      cytoplasmic TPI RNA levels were not affected by infection of HeLa cells with
      either Ad5 or H5dl1004. Steady-state levels of nuclear TPI RNA, both spliced and
      unspliced, were slightly reduced in cells infected by wild-type virus but not in
      HeLa cells infected by H5dl1004. These results indicate that the reduced
      stability of RNA in HeLa cells infected by E4 mutants is a virus-specific
      phenotype which does not extend to host cell RNAs.

PMID- 1994581
TI  - Nucleotide sequence of a gene essential for viral DNA replication in the
      baculovirus Autographa californica nuclear polyhedrosis virus.
AB  - The nucleotide sequence of the 60.1- to 65.5-m.u. region of Autographa
      californica nuclear polyhedrosis virus (AcMNPV) was determined. Seven large open
      reading frames were identified. Two open reading frames potentially encoding gene
      products of 143 and 38 kDa were found in the counterclockwise direction upstream
      of the p6.9 gene. Four additional open reading frames were found in the opposite
      direction. Analysis of the predicted amino acid sequence of the 143-kDa gene
      revealed a potential leucine zipper motif, a putative nuclear localization
      signal, and seven amino acid motifs previously identified in a number of proteins
      involved in NTP binding and DNA/RNA unwinding. The mutation in a DNA replication
      defective temperature-sensitive mutant was fine mapped to the carboxy terminus of
      the ORF1(p143) gene. Sequence analysis of the mutation site identified a single
      base change of a guanine to an adenine, resulting in the substitution of a
      methionine for valine. This mutation resides seven amino acids downstream of the
      putative NTP-binding motif of the ORF1(p143) gene product and results in a DNA
      negative mutant. Together these data strongly suggest that the ORF1(p143) gene
      product is a baculovirus helicase.

PMID- 1994582
TI  - Large-scale purification of membrane-containing bacteriophage PRD1 and its
      subviral particles.
AB  - PRD1 is a dsDNA virus that infects Escherichia coli and Salmonella typhimurium.
      The genome is a linear molecule with 5' covalently linked terminal protein. The
      virus has a lipid membrane inside the protein coat. We describe the large-scale
      purification of the virus using a zonal rotor and the yields and quality of the
      virus and its subviral assemblies for subsequent biophysical measurements.

PMID- 1994583
TI  - Myristylation of a duck hepatitis B virus envelope protein is essential for
      infectivity but not for virus assembly.
AB  - In addition to the major surface (S) protein, the envelope of the duck hepatitis
      B virus (DHBV) contains a related presurface (preS) protein whose N-terminus
      bears a covalently attached myristate group. We have explored the functional
      significance of this modification by examining the replicative potential of a
      mutant viral genome whose myristylation signal has been inactivated. Following
      transfection into permissive hepatoma cells, the mutant expresses an
      unmyristylated preS protein of normal size, immunoreactivity and stability.
      Cytoplasmic cores containing viral DNA are synthesized, and Dane particles are
      assembled and exported into the medium. However, the mutant is noninfectious when
      inoculated into susceptible ducklings. We conclude that myristylation of preS
      proteins is essential for hepadnaviral infectivity but not for viral assembly;
      myristylation is most likely required for an early step of the life cycle
      involving the entry or uncoating of virus particles.

PMID- 1994584
TI  - Variations of nucleotide sequences and transcription of the SH gene among mumps
      virus strains.
AB  - We have compared nucleotide sequences of the SH genes as well as their flanking
      regions of six mumps virus strains and found a high amino acid diversity (up to
      23%) of the putative SH proteins among these strains. It was found, in addition,
      that one of these strains (Enders strain) contained a point mutation in putative
      polyadenylation signal for the F gene mRNA (TTTAGAAAAAAA to TTTAGAAGAAAA).
      Northern blot analysis showed that the Enders strain was also unique in that
      neither monocistronic SH nor bicistronic SH-HN mRNA could be detected in the
      cells infected with this particular strain.

PMID- 1994585
TI  - Long terminal repeats of dwarf hamster endogenous retrovirus are highly diverged
      and do not maintain efficient transcription.
AB  - Recently we described a new endogenous proretrovirus of dwarf hamster Phodopus
      sungorus (MRS-Ps). Its sequence possesses evident homology with the endonuclease
      domain of the mouse mammary tumor virus pol gene. Here we present nucleotide
      sequence data on three clones of retroviral long terminal repeats. As many as 15%
      of substituted, deleted, and inserted base pairs were found while comparing these
      sequences. Hence, MRS-Ps seems to be rather an old genetic element which
      originated about 30 million years ago. One LTR is 877 bp long and contains
      numerous elements that control its transcriptional activity: TATA-box,
      glucocorticoid responsive element, NF1-binding site, etc. Nevertheless, this LTR
      does not govern efficient transcription of adjacent genes in a transient
      expression assay. In addition, we failed to find MRS-specific mRNA in adult,
      embryonic, and mammary tumor cells.

PMID- 1994586
TI  - Vaccinia virus encodes a protein with similarity to glutaredoxins.
AB  - Recently, we have reported the complete nucleotide sequence of vaccinia virus
      (Goebel, S. J., Johnson, G. P., Perkus, M. E., Davis, S. W., Winslow, J. P., and
      Paoletti, E. 1990, Virology 179, 247-266). Approximately 2.2 kbp leftward of the
      large subunit of ribonucleotide reductase resides a 108-amino acid open reading
      frame, O2L (nt 62,851-62,528) with significant similarity to known glutaredoxins.
      The deduced amino acid sequence of open reading frame O2L is 28.7% identical to
      the yeast and Escherichia coli proteins and greater than 40% identical to various
      mammalian glutaredoxins. Similar patterns of hydrophobicity as well as alpha
      helix and beta-sheet potentials suggest that O2L and the glutaredoxins share a
      similar secondary structure. Furthermore, a common function is inferred by the
      presence of a highly conserved redox-active site.

PMID- 1994587
TI  - Identification of the maize chlorotic mottle virus capsid protein cistron and
      characterization of its subgenomic messenger RNA.
AB  - Maize chlorotic mottle virus (MCMV) is a 30-nm icosahedral plant virus composed
      of a single 25-kDa capsid protein component and a 4.4-kb single-stranded,
      positive-sense genomic RNA. Northern blot hybridization analysis detected a
      single 3'-terminal 1.1-kb subgenomic RNA in infected plants. Virion RNA directs
      the synthesis of several polypeptides in a rabbit reticulocyte lysate in vitro
      translation system of which only the 25-kDa polypeptide is immunoprecipitated by
      MCMV capsid protein antiserum. The 1.1-kb subgenomic RNA is a highly efficient
      messenger RNA for capsid protein synthesis. Positive polarity in vitro
      transcripts from 3'-proximal MCMV cDNA clones direct the synthesis of the capsid
      protein in in vitro translation experiments. These data suggest that the MCMV
      capsid protein is expressed from a subgenomic RNA in vivo, and that the 25-kDa
      capsid protein is encoded by the 3'-proximal open reading frame in the MCMV
      genome.

PMID- 1994588
TI  - The C-terminal half of the preS1 region is essential for the secretion of human
      hepatitis B virus large S protein devoid of the N-terminal retention sequence.
AB  - A large surface protein of human hepatitis B virus was expressed from a mutated S
      gene in which both the reported retention sequence (aa 2-19) and the C-terminal
      half of the preS1 region (aa 66-117) were deleted. This retention sequence-free
      protein was not secreted from the monkey kidney cell line COS-M6 in transient
      expression assays. When this large S protein was overexpressed in the presence of
      the major S protein, the secretion of the latter was severely inhibited.
      Moreover, the presence of S protein in large abundance did not facilitate the
      secretion of the mutated large S protein at all, indicating that it was subject
      to more profound retention than the wild-type large S protein. The findings that,
      like the wild-type large S protein, this altered protein retained some of the
      properties of its C-terminal S domain, and that the preS1 region was still on its
      surface suggested that there was no extensive alteration of the polypeptide
      folding. The interpretation is favored that the C-terminal half of the preS1
      region plays a crucial role in the secretion of the large S protein when its N
      terminal retention sequence is not present.

PMID- 1994589
TI  - Small cysteine-rich proteins of different groups of plant RNA viruses are related
      to different families of nucleic acid-binding proteins.
AB  - The 3'-terminal genes in genomic RNAs of four groups of plant positive strand RNA
      viruses (hordei-, furo-, tobra-, and carlaviruses) encode small proteins enriched
      in Cys residues. The arrangement of Cys and in some cases also His residues in
      these proteins is compatible with finger formation. A computer-assisted sequence
      comparison of viral Cys-rich proteins reveals no significant similarity between
      them. It is shown that the hordeivirus Cys-rich protein (17K) is related to a
      group of chloroplast tRNA intron-encoded proteins, whereas the respective
      furovirus protein (14K) is similar to E6 proteins of papillomaviruses. Somewhat
      less significant similarity, marked, however, by conservation of a number of
      positively charged residues, was observed between the sequences of tobravirus Cys
      rich proteins and the basic domains of high mobility group chromatin proteins. It
      can be speculated that plant RNA virus Cys-rich proteins bind RNA and/or DNA and
      might be involved in regulation of virus and/or host genome expression. In the
      course of evolution these virus proteins may have originated from different
      nucleic acid-binding proteins.

PMID- 1994590
TI  - Are the acid-labile interferon alpha and interferon omega-1 identical?
AB  - The interferon (IFN) activity found in human leukocyte IFN alpha preparations,
      autoimmune and AIDS sera, and others was reported to have distinct antigenic and
      deviating biological properties. This led to its vague designation as acid-labile
      and thermolabile IFN alpha. However, using specific monoclonal antibodies, the
      acid-labile component of IFN alpha (not exposed to pH 2) and recombinant IFN
      omega 1 showed significant relatedness. Monoclonal antibody T19, generated with
      virus-induced leukocyte IFN alpha that had not been exposed to pH 2, neutralized
      both the antiviral and antiproliferative activities of IFN omega-1, and vice
      versa; monoclonal antibody OMG 5, specific for recombinant IFN omega-1, cross
      neutralized the antiviral and antiproliferative effects of the acid-labile
      component of leukocyte IFN alpha. When these two IFN preparations were incubated
      at pH 2 for 72 hr, their biological activity significantly decreased.

PMID- 1994591
TI  - Exclusion bypass of a difficult abdominal aortic aneurysm.
AB  - Aortic repair by graft replacement is currently the most generally accepted and
      widely used technique in the treatment of infrarenal abdominal aortic aneurysm.
      Many alternative approaches have been considered in order to limit the
      physiological stress of surgery. A recently described technique involves an
      extraperitoneal approach to the abdominal aorta, whereby the aneurysm is left in
      situ, excluded from arterial pressure, and an infrarenal aortic bypass is
      performed. In this case report, this exclusion bypass technique was safely
      applied through a transperitoneal approach to manage a very large, tortuous and
      displaced infrarenal abdominal aortic aneurysm which was densely adherent to the
      left kidney and ureter.

PMID- 1994592
TI  - Post menopausal bleeding as a risk factor for endometrial carcinoma.
AB  - From July 1985 to January 1989, 133 patients underwent endometrial sampling for
      evaluation of post menopausal bleeding (PMB). Of these patients, 114 (85.7
      percent) showed benign histology with an average age of 58.6 years. Nineteen
      (14.3 percent) were malignant, all of which showed endometrial carcinoma. The
      average age was 65. In addition, 26.3 percent of patients with carcinoma had
      higher grade of tumor at hysterectomy when compared with the preoperative biopsy.
      The average volume of tissue removed at curettage was significantly greater in
      those with carcinoma. Hormonal therapy, duration of symptoms, hypertension,
      obesity or diabetes were not significant risk factors for carcinoma in our
      series. PMB remains a major symptom that may predict endometrial carcinoma and
      must be evaluated. In those patients with carcinoma, intraoperative evaluation of
      the uterus for tumor grade and depth of invasion is important in determining the
      extent of surgery.

PMID- 1994593
TI  - Retroperitoneal drainage in the management of the septic phase of severe acute
      pancreatitis.
AB  - Eighteen consecutive patients with sepsis due to surgically confirmed
      peripancreatic necrosis extending diffusely into the retroperitoneal fat were
      treated in our hospital from 1980 to 1987. Management consisted of early
      retroperitoneal debridement of necrotic tissue and drainage through lumbar
      incisions. Enteral nutrition was implemented in all patients 3-8 days after their
      first surgery. A total of 40 reoperations were required--an average of 2.6 per
      patient. Complications included respiratory failure (17), renal failure (4),
      gastrointestinal bleeding (4), retroperitoneal bleeding (1), and gastrointestinal
      fistulas (6). Four (22%) of the 18 patients died; the major cause of death was
      multiple organ failure secondary to sepsis. Before 1980, all patients with severe
      pancreatitis treated in our hospital died, despite the use of different
      management techniques. The use of the extraperitoneal route for early debridement
      of necrotic tissue and to avoid contamination of the peritoneal cavity has
      substantially reduced the mortality associated with peripancreatic necrosis in
      our hospital. The mortality in this series of patients (22%) compares very
      favorably with that reported in studies of similar patients.

PMID- 1994594
TI  - Surgical treatment of severe postshunt hepatic encephalopathy.
AB  - Hepatic encephalopathy is a major complication of portal-systemic shunts with an
      incidence ranging up to 52%. A small fraction of these patients are refractory to
      medical therapy. Shunt ligation and colonic procedures are the main surgical
      approaches. The goal of the latter is to diminish the colonic absorption of
      nitrogenous substances which are involved in the pathophysiology of hepatic
      encephalopathy. Six patients, whose average age was 55.7 +/- 2.6 years, were
      operated for severe postshunt encephalopathy requiring 4.3 +/- 0.9 admissions for
      a total duration of 76 +/- 26 days over 1-11 years. One patient had undergone a
      splenoral shunt and 5 had a portacaval shunt. One ligation of the shunt and 5
      colon exclusions were performed. The average postoperative hospital stay was 21.5
      +/- 3.9 days. The mean follow-up was 47 +/- 20 months. The patient with the shunt
      ligation remains free of encephalopathy 94 months after the procedure and has not
      bled from his esophageal varices. Among the 5 colon exclusion patients, there
      were 1 death and 3 complications. Three patients were completely relieved of
      their hepatic encephalopathy. One of those 3 died of a subarachnoid hemorrhage 28
      months after the surgery. The fourth still needs medication to control a
      persistent, although improved, encephalopathy that required 2 further
      hospitalizations. Colon exclusion is a useful intervention in very selected
      cases. It has a lower operative mortality than total colectomy and the advantage
      over shunt ligation of not reestablishing hypertension in the portal system.

PMID- 1994595
TI  - Lower esophageal sphincter characteristics and esophageal acid exposure following
      partial or 360 degrees fundoplication: results of a prospective, randomized,
      clinical study.
AB  - In a prospective, randomized, clinical trial, we compared a partial (180-200
      degrees, Toupet) with a total fundoplication (360 degrees, Rossetti) in the
      surgical treatment of gastroesophageal reflux disease. Seventy-one patients
      entered the trial; 33 were allocated to a partial fundoplication and 38 to a 360
      degrees fundic wrap. Each patient was investigated prior to as well as 3 and/or 6
      months after the operation, including an endoscopic and clinical assessment.
      Manometry was carried out via a triple lumen catheter and the pressure in the
      high pressure zone (HPZ) in the distal esophagus was measured as well as the
      length of the intraabdominal segment by a "station pull-through" technique. Acid
      exposure of the esophageal mucosa was evaluated by ambulatory 24-hour pH
      measurements. Acid exposure of the esophageal mucosa was "normalized" by the 2
      operations. In addition, the length of the HPZ was increased to a "normal" level
      by both operations. The pressure of the HPZ was, however, "normalized" only in
      patients allocated to a Rossetti fundoplication, whereas patients operated on
      with a partial fundoplication had a significantly lower HPZ pressure (p less than
      0.01). The clinical assessment revealed excellent results in both groups with no
      significant differences between the 2 operations except for a higher incidence of
      dysphagia at 3 months after a Rossetti fundoplication (p less than 0.01), which
      disappeared during the subsequent 3 months.

PMID- 1994596
TI  - Scintigraphic detection of gastric and pancreatic carcinomas with In-111 ZCE 025
      monoclonal antibody.
AB  - We have evaluated the role of In-111 anti-CEA (carcinoembryonic antigen)
      monoclonal antibody ZCE 025 in 8 patients. Three patients had a confirmed
      diagnosis of gastric carcinoma. Three had a confirmed diagnosis of pancreatic
      carcinoma. Two patients had elevated serum levels of CEA with no known primary.
      Each patient received 5.5 mCi In-111 ZCE 025 infused at doses of 10-80 mg. Planar
      and single photon emission computed tomography (SPECT) imaging at 3 and 7 days
      after infusion detected 9 of 12 known tumor sites and all 5 of the previously
      identified sites of metastasis. In-111 ZCE 025 MoAb imaging also found 6
      previously unsuspected tumor sites and changed the preoperative evaluation in 50%
      of the patients studied. It changed the clinical management in 2 patients and
      established the site of primary involvement in 2 others. There were no clinical
      or biochemical reactions. In-111 ZCE 025 monoclonal antibody scintigraphy is a
      useful adjunct in the evaluation of patients with either gastric or pancreatic
      carcinoma. It may have a beneficial impact on the surgical decision making in
      these patients.

PMID- 1994597
TI  - Cervicothoracic arterial injuries: recommendations for diagnosis and management.
AB  - Management of arterial injuries at the thoracic outlet and neck presents a major
      challenge to the trauma surgeon: hemorrhagic shock, neurologic deficit, and limb
      loss are the serious sequelae. Over a 13-year period, 118 patients with injuries
      to the innominate, carotid, subclavian, and axillary arteries were evaluated.
      Most injuries were penetrating (78%). Half of the patients were diagnosed by
      physical examination and half by angiography. Patients were treated by either
      primary repair (35%), interposition graft (31%), ligation (8%), or
      anticoagulation (26%). Two patients required amputations (1 digit, 1 above
      elbow). Overall mortality was 14%, with 5% due to consequences of hemorrhagic
      shock, 7% due to cerebral ischemia, and 2% due to other causes. Claviculectomy,
      median sternotomy, and trap door incisions were routinely used for proximal
      vascular control and repair. We conclude that liberal use of angiography is
      indicated in stable patients for penetrating wounds near major arteries, and for
      blunt injuries associated with neurologic deficits unexplained by computed
      tomography. Patients with obvious arterial injury should have immediate
      exploration. Extensile exposure is mandatory for appropriate management. Blunt
      carotid dissections are generally best managed non-operatively with
      anticoagulation.

PMID- 1994598
TI  - Endoscopic treatment of adenomas.
AB  - The endoscopic removal of colon polyps can be safely and efficiently accomplished
      when established principles of colonoscopy and electrosurgery are followed. This
      technique requires the proper equipment, a skilled endoscopy assistant, and a
      well-trained, experienced endoscopist. Complete mastery of basic colonoscopy is
      essential along with an understanding of the concepts of electrocautery and
      knowledge concerning the structural configurations of polyps.

PMID- 1994599
TI  - Complicated pneumothorax: short- and long-term results of endoscopic fibrin
      pleurodesis.
AB  - Complicated pneumothorax is defined as a recurrent or persistent air leak in the
      pleural interspace beyond 5 days despite adequate tube drainage. Up to now, this
      disorder could only be corrected by open thoracotomy. Endoscopic fibrin
      pleurodesis is shown to be a method that could obviate, in most cases, the need
      for thoracotomy. In the last 6 years, 138 of 153 patients presenting with
      complicated spontaneous pneumothorax were treated with this method. The fibrin
      sealant consists of 2 components: fibrinogen, factor XIII, and albumin dissolved
      in aprotinin (3,000 KIU/ml), and a thrombin calcium chloride solution, which is
      applied through the working channel of a thoracoscope and vaporized with nitrous
      oxide. In this observation period, 6 (4.4%) recurrences were observed, which were
      subsequently treated with thoracotomy; a second attempt at fibrin pleurodesis was
      not undertaken. In all cases, endoscopic sealing was followed by prompt
      reexpansion of the collapsed lung. Long-term follow-up was satisfactory,
      pulmonary function tests showed no signs of restrictive dysfunction, and pleural
      fibrosis was not observed on x-ray as reported in other modes of treatment.
      Following these results, it is concluded that this method is useful in cases of
      persistent, therapy-resistant, complicated spontaneous pneumothorax; its effects
      are durable and it has a low rate of recurrence. It produces a physiological
      healing process without damage to the pleura.

PMID- 1994601
TI  - Follow-up after polypectomy.
AB  - Progress in understanding the biology, natural history, and relationship to
      colorectal cancer has provided the basis for a rational approach to patients with
      adenomas. Pathological assessment of polyps is essential for initial management;
      only adenomas require search for synchronous neoplasia. A finding of a 30%-50%
      synchronous rate has been observed. After clearing of the colon of all adenomas,
      follow-up examination will reveal a 30%-50% rate of metachronous adenomas, but
      usually with unimportant pathology. Patients with no special concerns at initial
      polypectomy can have surveillance at intervals of approximately 3 years, while
      those with an incompletely cleared colon, numerous polyps, or large sessile or
      malignant adenomas need individualized surveillance. Working guidelines can be
      provided at this time pending observations in ongoing trials. It is expected but
      not yet proven that control of colonic adenomas will reduce the incidence and
      mortality from colorectal cancer. Further research into the biology of adenomas
      and cancer will undoubtedly provide a clear understanding of susceptibility for
      colorectal adenomas and more selective control strategies.

PMID- 1994600
TI  - Surgical treatment of adenomas.
AB  - Surgical treatment of adenomas may become necessary when the base of the polyp is
      too wide for snaring, increasing the risk of incomplete removal or perforation of
      the bowel wall. Suspicion of malignancy may also indicate surgery. Multiple
      adenomas not controlled by snare polypectomy can be treated by colectomy. The
      different approaches of surgical treatment are described.

PMID- 1994602
TI  - Intervention studies in adenoma patients.
AB  - There is considerable evidence that most colorectal carcinomas arise in
      preexisting adenomas. It also appears that there may be a considerable influence
      of diet in the genesis and growth of adenomas. This evidence is discussed and the
      current dietary intervention studies in humans are reviewed.

PMID- 1994603
TI  - Natural history of adenomas.
AB  - One-third of individuals over the age of 55 years have single or multiple
      colorectal adenomas. During a subsequent period of 10 years, 3-5% of adenoma
      bearing individuals will probably develop a carcinoma. The rather low conversion
      rate from benign to malignant disease indicates that most individuals with
      adenomas will never develop colorectal carcinoma. More knowledge is required to
      predict the outcome of the individual adenoma in a given patient. This will
      probably be obtained by increasing progress within gene technology and through
      large prospective follow-up studies of adenoma-bearing patients.

PMID- 1994604
TI  - Treatment of carcinoma in adenomas.
AB  - Invasive carcinomas in polyps removed during endoscopy are described. Most of
      them can be treated adequately by polypectomy alone, but some need additional
      surgical treatment. Incomplete excision, poorly-differentiated carcinoma, and
      lymphatic invasion are associated with increased risk of residual carcinoma and
      lymph node metastases, making colorectal resection more attractive; however, in
      elderly patients and poor-risk patients, the risks of surgery should be balanced
      against the possible advantage of curative surgery. Rectal polyps may be large
      but sphincter preservation can usually be achieved by different types of local
      excision. Recently described flat adenomas may contain carcinoma, but may also be
      treated by polypectomy using snare or hot biopsy.

PMID- 1994605
TI  - Other gastrointestinal polyps.
AB  - Gastrointestinal polyp is a descriptive concept--observation of an elevated broad
      based or stalked lesion which can be defined exactly only when examined
      histologically. Therefore, all polyps must, in principle, be snared or excised to
      achieve a final diagnosis. Nonneoplastic polyps or tumor-like lesions were
      formerly considered innocent findings with no malignant potential, while
      neoplastic adenomas with dysplasia are well-known premalignant lesions. This view
      of the totally harmless nature of nonneoplastic polyps is no longer true. At
      least the dominantly inherited juvenile polyposis and Peutz-Jeghers polyposis
      syndromes definitely have malignant potential through adenomatous change in the
      originally hamartomatous lesions. Consequently, juvenile polyposis is best
      treated with colectomy and ileorectal anastomosis, and repeated multiple
      polypectomies are now recommended in Peutz-Jeghers polyposis, in combination with
      laparotomy when feasible. In addition, hyperplastic gastric polyps may reflect an
      underlying atrophic gastritis implying increased risk of gastric carcinoid tumors
      and cancer. Furthermore, even colorectal hyperplastic polyps may undergo
      adenomatous change, and thus represent, theoretically, a reservoir from which
      adenomas arise.

PMID- 1994607
TI  - Resection of synchronous liver metastases from colorectal cancer.
AB  - Whereas resection for metachronous liver metastases from colorectal cancer is
      considered to be a potentially curative approach, little is known about the
      prognosis after resection of synchronous liver metastases. In the past, these
      patients usually underwent only palliative therapy. Therefore, we have analyzed
      the data of 36 patients who underwent curative hepatic resection of synchronous
      liver metastases from colorectal carcinomas from 1977 to 1987 at the Department
      of Surgery, Hannover Medical School. In 19 patients, liver resection was combined
      with colonic resection; in the other 17 patients, hepatic resection was performed
      after a median interval of 2 months following resection of the primary tumor. No
      operative mortality was observed in either of the approaches. The median survival
      time was 28 months for all patients with a median recurrence-free interval of
      13.5 months. Overall 5-year survival probability for all patients was 20%. There
      were no significant differences observed between immediate or delayed liver
      resection (median survival 18 months versus 31 months). Survival rates were not
      different after resection of solitary versus multiple liver metastases (26 versus
      28 months). Twenty-one of the 36 patients had a recurrence of their liver
      metastases. In 7 of them, curative liver resection could be performed again.
      These 7 patients had a significantly improved survival (p less than 0.05)
      compared to the residual 14 patients. It is concluded that patients with
      synchronous liver metastases from colorectal cancer may profit from resection of
      the primary tumor and liver metastases. Timing of liver resection--immediate
      versus delayed--obviously has no impact on survival rates.

PMID- 1994606
TI  - Bleeding esophageal varices associated with pancreatic arteriovenous
      malformation.
AB  - Three cases of bleeding esophageal varices associated with arteriovenous
      malformation of the pancreas have been observed over the last 7 years. In 1 case,
      arteriovenous malformation (AVM) was the cause of the portal hypertension; thus,
      it was considered to be a "primary lesion." In the other cases, liver cirrhosis
      was the cause of the portal hypertension, and the AVM, which originally was a
      minor pathology, became significant as the portal hypertension progressed, thus
      making it a "secondary lesion." In the case of a "primary lesion," resection of
      the lesion is the preferred treatment for bleeding varices, but our case had
      multiple lesions, and excision was problematic. In the case of bleeding varices
      caused by liver cirrhosis, if liver function is normal, surgical treatment of
      both the varices and the AVM is recommended, while if the liver function is
      abnormal, repeated sclerotherapy is the best mode of therapy.

PMID- 1994608
TI  - Management of acute volvulus of the sigmoid colon: a new approach by percutaneous
      deflation and colopexy.
AB  - Forty-one consecutive patients with acute sigmoid volvulus were prospectively
      randomized into 2 groups to compare percutaneous deflation prior to emergency
      tube decompression followed electively by colopexy with banding (n = 20) versus
      emergency tube decompression followed electively by sigmoid colectomy (n = 21).
      Of 21 patients subjected to tube decompression, the procedure was successful in
      15 (71%). Emergency sigmoid colectomy was done in the remaining 6 patients and 3
      of them died postoperatively. Percutaneous deflation enabled all patients (n =
      20) to have successful tube decompression without complications. Two of the
      patients (13%) who underwent elective sigmoid colectomy died postoperatively and
      another 2 developed wound infections, whereas colopexy by banding caused no
      mortality and only 1 patient (5%) developed a wound infection. Disconnection of
      the intravenous line, consumption of solid food, and discharge from the hospital
      were each effected at significantly (p less than 0.001) earlier postoperative
      times with colopexy than with sigmoid colectomy. Both of these elective
      procedures were equally effective in preventing recurrence of the volvulus.
      During 1 year of follow-up, colopexy was not observed to cause any abdominal pain
      or alteration in bowel habits. This study shows that percutaneous deflation of
      acute sigmoid volvulus is a rapid and safe method which enables successful
      sigmoidoscopic decompression with avoidance of emergency surgery and its high
      mortality rates. The study also shows that colopexy by banding is a simple
      elective procedure which overcomes the limitations of mesenteropexy and
      resectional surgery.

PMID- 1994609
TI  - Adenomas and hyperplastic polyps in screening studies.
AB  - A survey is given of colorectal polyps detected in a prospective randomized
      screening study with the fecal occult blood test. It is demonstrated that
      colonoscopy in persons with positive Hemoccult-II tests results in detection of
      and removal of a higher number of adenomas than among controls. The strategy may,
      therefore, possibly be followed by a reduction of the incidence of colorectal
      cancer. Screen-detected adenomas were most often in males and were larger than
      among controls; they were most often in the sigmoid colon, whereas the rectum was
      the most frequent location for adenomas in controls. Eight percent of persons
      with screen-detected adenomas had some symptoms, which could be referred to
      adenomas, in contrast to 50% among controls. Hyperplastic polyps served as
      markers for adenomas in persons with positive Hemoccult-II as well as in controls
      with adenomas detected by colonoscopy; however, most persons with adenomas had no
      hyperplastic polyps. Endoscopic polypectomy did not result in any severe
      complications, but surgical removal in 2 of 22 patients proved fatal. The results
      presented are compared with those of other prospective randomized trials. The
      optimistic view--that the incidence of cancer may be reduced by polypectomy in
      persons with positive Hemoccult-II tests--stresses the importance of securing
      optimal colonoscopy service.

PMID- 1994610
TI  - Sequential abdominal reexploration with the zipper technique.
AB  - Frequently, several multiple abdominal reexplorations are needed in patients with
      acute necrotizing hemorrhagic pancreatitis (ANP) or with persistent
      intraabdominal sepsis (PIAS). Residual undrained necrotic and septic foci lead to
      multiple organ failure. To provide wide-open drainage of the abdominal cavity,
      since 1985 we have performed sequential abdominal reexploration with the zipper
      technique (SARZT) in 24 patients. Apache II score was used to evaluate expected
      mortality. In the pancreatic necrosis group, with a mean Apache II score of 31,
      the expected and the observed mortality were 70% and 29%, respectively. In the
      PIAS group, with a mean Apache II score of 30, the expected and observed
      mortality were 60 and 28%, respectively. These results are attributed to the
      sequential reexploration of the abdominal cavity that permits excision and
      drainage of necrotic and septic foci.

PMID- 1994611
TI  - Primary jejunoileal tumors: a review of 45 cases.
AB  - We reviewed 45 patients who underwent surgery for primary jejunoileal tumors over
      a 15-year period. There were 16 benign and 29 malignant tumors, which included 13
      lymphomas, 7 adenocarcinomas, 7 carcinoid tumors, and 2 leiomyosarcomas. Eighteen
      patients, 13 of whom had benign tumors, presented with intestinal bleeding and 5
      tumors were found incidentally at laparotomy. Benign lesions were more frequently
      sited in the jejunum while malignant lesions were more common in the ileum (p
      less than 0.001). Lesions presenting with hemorrhage were more likely to be
      benign than malignant (p less than 0.001) and were more commonly sited in the
      jejunum than in the ileum (p less than 0.05). Visceral perforation (31%),
      intestinal obstruction (21%), and an abdominal mass (17%) were other presenting
      features in patients with malignant tumors. In spite of a wide variety of
      investigations, the correct diagnosis was reached preoperatively in only 31% of
      patients. Surgical management included either limited bowel resection or
      segmental resection with regional lymphadenectomy. Operative mortality was 13%
      and morbidity was 36%. Actuarial 5-year survival for all malignant tumors was
      24%, being 64% at 5 years for carcinoid tumors, 20% at 30 months for
      adenocarcinomas, and 10% at 42 months for lymphomas. These results reemphasize
      the need for a high index of suspicion and early laparotomy in patients with
      obscure intestinal symptoms if the prognosis of small bowel tumors is to improve.

PMID- 1994612
TI  - Falls in hemoglobin saturation during ERCP and upper gastrointestinal endoscopy.
AB  - Fiberoptic endoscopy is practiced everyday in the field of gastroenterology and,
      for diagnostic purposes, carries a risk of complications and an estimated
      mortality of 1:5,000, which is multiplied several times during interventional
      procedures. Half of these complications have a cardiopulmonary origin which may
      be anticipated by the use of pulse oximetry to measure hemoglobin saturation
      (SaO2). We studied 132 patients undergoing diagnostic or procedural endoscopic
      retrograde cholangiopancreatography (ERCP) under sedation, and 51 undergoing
      esophagogastroduodenoscopy (EGD) without sedation. In the ERCP group, SaO2 fell
      from 95.7 +/- 2.4% (mean +/- standard deviation) to 88.9 +/- 6.4% (p less than
      0.001) with a corresponding rise in pulse from 95 +/- 19 to 116 +/- 18/min (p
      less than 0.001) followed by recovery. The largest falls followed positioning of
      the endoscope (rather than following administration of the sedative or the
      procedure), particularly during introduction of the endoscope within 1 minute of
      administering diazemuls (diazepam). The EGD group also had a fall in SaO2 (97.3
      +/- 1.9% to 93.9 +/- 3.3%, p less than 0.001), although the patients were younger
      and undergoing shorter examinations. Again, the largest falls occurred 1 minute
      after introduction of the endoscope. In subgroups of patients undergoing ERCP,
      analysis of respiratory patterns using spectral techniques and electrocardiogram
      during endoscopy (n = 25), or peripheral perfusion using transcutaneous oximetry
      and laser Doppler velocimetry (n = 12) was undertaken. No correlations were found
      in relation to changes in SaO2. The cause of the fall in SaO2 during endoscopy is
      multifactorial.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1994613
TI  - Body composition in Chinese subjects: comparison with data from North America.
AB  - A multiple tracer dilution method measuring total body water, extracellular
      water, plasma volume, and red cell volume was used to study body composition.
      Healthy Chinese subjects were compared to a group of Chinese patients with
      various newly diagnosed gastrointestinal disorders scheduled for elective
      operation. Compositional data obtained from these groups showed no significant
      differences in compartmentalization, suggesting absence of major changes during
      the early stages of certain gastrointestinal diseases. In addition, healthy
      Chinese subjects were compared to a group of healthy Americans previously
      evaluated by similar dilutional methods. In males, body weight (kg) differed
      considerably (Chinese = 62.1 +/- 2.0 versus American = 72.5 +/- 4.1, p less than
      0.02) and could be explained by alterations in body fat (Chinese = 12.4 +/- 1.3
      versus American = 19.2 +/- 2.2, p less than 0.02) and extracellular water
      (Chinese = 14.4 +/- 0.5 versus American = 16.8 +/- 0.8, p less than 0.02).
      Functional tissue ("body cell mass") was similar in the 2 groups which suggested
      that Chinese have comparable body composition without an additional fat burden.
      The multiple tracer technique using deuterium oxide, sodium bromide, Evans dye,
      and Cr51 for body compositional assessment is accurate but expensive and
      laborious. Therefore, equally precise but more economical bedside methods are
      needed for routine compositional analysis.

PMID- 1994615
TI  - Cervicovaginal cytopathology in honor of George L. Wied on his 70th birthday.

PMID- 1994614
TI  - [Identification and quantitative determination of currently important plant
      protectants by HPTLC].
AB  - This systematic study describes the determination of approximately 150 pesticides
      (mainly insecticides and fungicides) on high-performance thin-layer
      chromatography (HPTLC) layers, using modern techniques for spotting and
      evaluation. Standardized mobile phases and reagents for visualization form the
      basis for the confirmation of gas-chromatographic results by HPTLC. The very high
      sensitivity of cholinesterase inhibition can be utilized only on plates coated
      with silica gel. Several other currently important pesticides can be separated on
      C-18 reversed phase layers and detected using silver nitrate-UV irradiation or
      chlorine-o-tolidine. Computer-assisted densitometric evaluation allows direct
      quantitative determination of the pesticides.

PMID- 1994616
TI  - George L. Wied - seventy years young.

PMID- 1994617
TI  - Comparative study of cytology and punch biopsy in cervical intraepithelial
      neoplasia during pregnancy. A preliminary report.
AB  - To elucidate the accuracy of cytology in diagnosing cervical intraepithelial
      neoplasia (CIN) during pregnancy, cytologic screenings for uterine cervical
      cancer in pregnant women were reviewed for a five-year period. Of the 967
      pregnant women screened, abnormal cytologic findings were recorded for 15 (1.6%).
      Only nine of these were subsequently examined by colposcopy and punch biopsy,
      which demonstrated CIN in all cases, for an incidence of documented CIN during
      pregnancy of 0.93%. Including two referral cases also examined by colposcopy and
      biopsy, cytology and histology agreed on the degree of CIN in four cases and
      disagreed by one degree in four cases, by two degrees in two cases and by three
      degrees (mild dysplasia versus carcinoma in situ) in one case. Review of the
      specimens from these cases did not readily explain the poor concordance between
      cytology and punch biopsy; some findings suggest that overestimation of the punch
      biopsy sample may be the explanation.

PMID- 1994618
TI  - Residual trophoblastic tissue as a source of highly atypical cells in the
      postpartum cervicovaginal smear.
AB  - A cervicovaginal smear containing atypical cells, which were interpreted as
      dysplastic cells, was obtained from a women one-year postpartum. These cells were
      seen singly, in small groups and in clusters embedded in an amorphous pink
      matrix. They had amphophilic cytoplasm and increased nuclear/cytoplasmic ratios,
      as well as hyperchromatic nuclei with variably prominent nucleoli, features that
      are characteristic of trophoblastic cells. No evidence of dysplasia was seen on
      subsequent colposcopic examination or cervical biopsy. Endocervical curettage
      yielded fragments of exfoliated endometrium and residual trophoblastic tissue
      associated with a placental implantation site. Although involution of the
      placental site is generally complete by six to seven weeks postpartum, maternal
      fetal tissue may in fact continue to be exfoliated for several months or longer
      after delivery. If seen on a cervicovaginal smear, these cells can be highly
      atypical and may be mistaken as dysplastic or malignant. The cytologic features
      that characterize trophoblasts and their persistence in postpartum cervicovaginal
      smears are discussed.

PMID- 1994619
TI  - Morphology of adenocarcinoma in situ and microinvasive adenocarcinoma of the
      uterine cervix. A cytologic and ultrastructural study.
AB  - Adenocarcinoma in situ (AIS) and microinvasive adenocarcinoma of the uterine
      cervix and normal endocervical columnar epithelium were studied by cytology,
      morphometry and electron microscopy to identify differentiating features and to
      ascertain the cellular origin of cervical adenocarcinoma. Smears from AIS showed
      the characteristic cytology, consisting of glandular rosettes, palisading and
      crowded sheets; most nuclei had a relatively uniform oval shape. Smears from
      microinvasive adenocarcinoma showed more crowded sheets, with enlarged, round and
      irregular-shaped nuclei and prominent oval nucleoli. These nuclear features were
      confirmed by the morphometric results. Ultrastructurally, reserve cells in the
      normal tissues contained tonofibers and secretory granules and showed squamous
      and adenomatous features. The ultrastructural features of microinvasive
      adenocarcinoma were similar to those of well-differentiated invasive
      adenocarcinoma. The cells from both contained tonofibers and secretory granules.
      These findings suggested that the reserve cell is the cell of origin for cervical
      adenocarcinoma.

PMID- 1994620
TI  - Comparative cytologic features of adenocarcinoma in situ of the uterine cervix.
AB  - The cytologic findings in 30 cases of adenocarcinoma in situ (AIS) and related
      lesions of the cervix were compared with those in 13 cases of cervical invasive
      adenocarcinoma and 8 cases of cervical nonneoplastic conditions that mimicked AIS
      cytologically. Although there was considerable overlap, the presence of large
      cells with irregular nuclei and uneven chromatin distribution in smears
      containing no normal endocervical cells helped to distinguish invasive
      adenocarcinoma from AIS. The presence of "feathering," rosettes, mitotic figures
      and very crowded nuclei with scant cytoplasm and without cilia helped distinguish
      AIS from benign conditions.

PMID- 1994622
TI  - In memoriam. John Kingsbury Frost.

PMID- 1994621
TI  - Cervicovaginal cytology in uterine adenocarcinoma and adenosquamous carcinoma.
      Comparison of cytologic and histologic findings.
AB  - To investigate the diagnostic accuracy and to characterize the findings in false
      negative cases, the results of cervicovaginal cytology in 56 adenocarcinomas and
      25 adenosquamous carcinomas (42 cervical, 36 endometrial, 2 metastatic and 1
      arising synchronously from both cervix and endometrium) were reviewed, including
      review of the actual slides in 56 cases. Overall, 80% of the initial cytologic
      diagnoses resulted in diagnostic curettage (i.e., cytology was effectively
      positive); 84% of the postreview diagnosis were effectively positive. Nine
      cytology slides showed no malignant cells; eight of these negative smears showed
      repair, five were atrophic, two showed a high estrogen effect and one had
      enlarged atypical bare nuclei. These false-negative diagnoses were associated
      with an endometrial primary site (P less than .01), endometrioid histology (P
      less than .005), low-grade or intermediate-grade histology (P less than .005),
      small size of tumor (P less than .05) and absence of cervical involvement (P less
      than .005) in those cases in which a hysterectomy was performed. False-negative
      diagnoses were not associated with an absence of endocervical cells or with
      scanty cellularity. Of 39 cervical and 28 endometrial carcinomas with a positive
      cytologic diagnosis (initially or after review of the available slides), cytology
      correctly identified the primary site in 18% and 54% of the cases, respectively.
      Cytology incorrectly classified the anatomic site of four cervical and three
      endometrial carcinomas and considered one case arising in both the endometrium
      and cervix to be endometrial. Routine cervicovaginal cytology does have a role in
      screening for uterine glandular carcinoma; to maximize its diagnostic
      sensitivity, we suggest using a recommendation for curettage in the report of
      positive cases so that all of the varied cytologic diagnoses associated with
      glandular carcinomas will receive a uniform clinical response. In those cases
      with preserved cancer cells, a correlation can be made with the histologic type
      of the carcinoma, rather than with the anatomic site.

PMID- 1994623
TI  - Classics in cytology: IV. Traut and the "Pap smear".

PMID- 1994624
TI  - The clinical significance of Actinomyces colonization as seen in cervical smears.

PMID- 1994626
TI  - Toxoplasma gondii in a cervical smear.

PMID- 1994625
TI  - Cervical smear with intracellular organisms from a case of granuloma venereum
      (donovanosis)

PMID- 1994627
TI  - Aspiration findings of extramedullary hematopoiesis presenting as an epidural
      mass.

PMID- 1994628
TI  - Computerized reporting and follow-up of gynecologic cytology.
AB  - A system utilizing inexpensive computer hardware to produce high-quality cytology
      report and to provide an extensive, semi-automated follow-up system is described.
      Key features of the reports generated are emphasized. The system uses the
      Bethesda System nomenclature for reporting cytologic findings to a wide range of
      physicians, from general practitioners to gynecologists to subspecialists in
      gynecologic oncology.

PMID- 1994629
TI  - Information, discrimination and divergence in cytology. II. Total discrimination
      as a measure of performance.
AB  - Discrimination is the expectation of log odds ratios. Performance in diagnostic
      cytology, as compared to the results of histopathology or to a peer-reviewed
      consensus, can be measured by the total discrimination, which is a well-defined
      measure of information in information theory and test theory. The total
      discrimination, as a measure of performance, was calculated for the Gynecologic
      Cytology Laboratory of the University of Minnesota for the years 1985 through
      1987, based on 3,545 sets of single-slide Papanicolaou smears and colposcope
      directed biopsies. Similar calculations were made for the performances of
      physicians and technicians on peer-reviewed "clear-cut" Papanicolaou smears, as
      reported in a study from the Centers for Disease Control (CDC). For fair
      comparison of the two different sets of observations, the cytologic categories
      and corresponding histologic states were merged into five categories and states.
      The cytologic performance of our laboratory, tested against the histologic
      diagnoses, and the performances of the physicians and technologists tested
      against peer-reviewed check samples by the CDC were 0.53, 0.45 and 1.17 decits,
      respectively. These values generally agree with the conclusions derived by more
      conventional methods used by the CDC. When sampling errors of cytology specimens
      are taken into account, the performance of our laboratory, measured by the total
      discrimination of the cytology-histology confusion matrix, was approximately
      equal to the performance of the group of technologists studied by the CDC, which
      was in turn significantly better than that of the group of physicians studied by
      the CDC. This study demonstrates the value of using the total discrimination for
      quantifying the performance of a cytology laboratory, a cytopathologist or a
      cytotechnologist, without the arbitrary means usually used to evaluate such
      performances.

PMID- 1994630
TI  - False-positive and false-negative proficiency test results in cytology.
AB  - Proficiency tests in cytology classify a certain proportion of cytologists
      inaccurately. Some competent cytologists fail during the testing procedure
      ("false-negative proficiency test" or "type I error") while some individuals who
      should fail do pass the test ("false-positive proficiency test" or "type II
      error"). In other words, success or failure during proficiency testing may be the
      consequence of statistical chance. Calculations based on the binomial
      distribution are presented to show the seriousness of this problem. The analysis
      demonstrated that increasing the number of slides in the test sets does not
      necessarily improve the accuracy of the test. For instance, on the 90%
      ("borderline competent") level, raising the number of slides in one test set from
      10 to 20 reduced the accuracy of the test by 6%.

PMID- 1994631
TI  - Information, discrimination and divergence in cytology. III. Optimization of
      classification of Papanicolaou smears.
AB  - The performance of a cytology laboratory can be objectively quantitated as the
      total discrimination, a defined quantity of information. The total discrimination
      is dependent on the number of categories used in gynecologic cytology and on the
      corresponding histologic states; over-classification results in a higher rate of
      misinformation and reduced total discrimination. Total divergence is another
      measure of the association between cytologic categories and histologic states; in
      contrast to the total discrimination, the total divergence does not require a one
      to-one correspondence between the cytologic categories and the histologic states.
      Using data from the Gynecologic Cytology Laboratory of the University of
      Minnesota, the total discrimination was maximized when gynecologic cytology used
      three categories of diagnosis, consisting of (1) normal, atypical benign or
      reactive atypia, (2) cervical intraepithelial neoplasia (CIN) and (3) all
      malignancies. The use of four categories, (1) normal, atypical benign or reactive
      atypia, (2) mild or moderate dysplasia, (3) severe dysplasia or squamous
      carcinoma in situ and (4) all malignancies, was almost equally informative.
      Observations on the total divergences resulted in similar conclusions. These
      findings generally support the recommendation of the consensus workshop sponsored
      by the National Cancer Institute (the Bethesda System nomenclature) to group all
      degrees of CIN into two large categories.

PMID- 1994632
TI  - Information, discrimination and divergence in cytology. IV. Quality control in
      diagnostic cytology.
AB  - The performance of diagnostic cytology on Papanicolaou smears can be periodically
      monitored by calculating the total discrimination or the total divergence of the
      cytologic diagnoses against the histologic diagnoses on samples obtained by
      colposcope-directed biopsies. Using these measures, the annual performances of
      the Gynecologic Cytology Laboratory of the University of Minnesota between 1980
      and 1988 were retrospectively analyzed. For those years, the total discrimination
      and total divergence behaved similarly and were sensitive to the performance of
      the total system, including specimen sampling errors and laboratory precision.
      The lowest limits of the permissible range of the total discrimination and total
      divergence were 0.15 and -1.21 decits, respectively, for a single-slide
      Papanicolaou test if an 80% "hit" rate was accepted as the lowest threshold for
      each category. The optimal numbers of category-states were not a sensitive
      indicator of the quality of a laboratory; i.e., the optimal number of diagnostic
      categories remained at three throughout the period studied.

PMID- 1994634
TI  - Analysis of cervical smears obtained within three years of the diagnosis of
      invasive cervical cancer.
AB  - The cytologic histories of 376 women presenting with invasive carcinoma of the
      cervix were analyzed. In total, 202 (53.7%) of these women had had 355 smears
      taken during the three years preceding presentation. All 320 smears with an
      original cytologic diagnosis of less than cancer were reviewed. The original
      cytologic diagnosis was low in 95 (30.6%) of 310 adequate smears. Originally, 96
      (30.9%) of the adequate smears were evaluated as negative; at review, only 55
      (17.5%) of the adequate smears were evaluated as negative. Comparing the review
      diagnoses to the 355 total smears, the rates of negative smears were 13.5% (42 of
      310) for squamous-cell carcinoma, 30.0% (12 of 40) for adenocarcinoma and 20.0%
      (1 of 5) for adenosquamous carcinoma (P less than .05). The cellular composition
      of the smear was significantly related to the cytologic detection of
      abnormalities: endocervical cylindrical and/or metaplastic cells were seen in
      only 45.5% of smears diagnosed as negative, but in 84.4% and 97.8% of smears
      diagnosed as atypia and cervical intraepithelial neoplasia, respectively P less
      than .00001). Smears without endocervical cells should be considered inadequate
      and should be repeated.

PMID- 1994633
TI  - False-negative Papanicolaou smears from women with cancerous and precancerous
      lesions of the uterine cervix.
AB  - The occurrence from 1980 to 1989 of false-negative Papanicolaou smears in women
      with cancerous and precancerous lesions of the uterine cervix was studied. The
      4,781 cases of cancer (2,814 invasive carcinomas and 593 carcinomas in situ) and
      precancerous lesions (418 severe dysplasias, 748 moderate dysplasias and 208 mild
      dysplasias) included 70 cases (1.5%) with false-negative smears. These 70 cases
      included 43 invasive carcinomas (61.4%), 17 carcinomas in situ and
      adenocarcinomas in situ (24.2%), and 10 dysplasias (14.4%); all were diagnosed
      histologically. The mean age of women with false-negative smears was 44.1 +/-
      13.7 years. Review of the original cytologic samples showed a screening error in
      41 cases (58.5%), an interpretation error in 2 cases (2.9%) and a sampling error
      in 27 cases (38.6%). Methods for eliminating false-negative smears are discussed.

PMID- 1994635
TI  - Cervicovaginal cytology in an indigent population. Comparison of results for
      1964, 1981 and 1989.
AB  - To evaluate the usefulness of cervicovaginal cytology in decreasing the incidence
      of cervical carcinoma in an indigent population, the cytologic findings from
      10,000 consecutive smears in 1964 (when cytology screening started) were compared
      to the results of 10,000 consecutive smears in 1981 and 1989. There was a marked
      (statistically significant) decrease in invasive cervical squamous carcinoma at
      all ages between the first and later periods. Squamous carcinoma in situ showed a
      significant decrease beginning in patients under 40 in 1981. The number of
      atypias and mild dysplasias showed a proportional increase, from 2% in 1964 to
      13.4% in 1981 to 21.8% in 1989, predominantly in young patients. These results
      reaffirm that cervicovaginal cytology remains the most inexpensive and effective
      diagnostic tool for the elimination of cervical cancer.

PMID- 1994637
TI  - Comparison of Cytobrush sampling, spatula sampling and combined Cytobrush-spatula
      sampling of the uterine cervix.
AB  - Since the introduction of the Cytobrush for sampling the uterine cervix, some
      practitioners have ceased taking a concomitant cervical scraping using a spatula.
      To examine whether Cytobrush sampling alone is adequate for the diagnosis of
      cervical lesions, the Cytobrush and spatula samples in 444 smears (most with
      original diagnoses of at least mild dysplasia) were analyzed separately for the
      presence of diagnostic cells, endocervical cells and squamous cells. Of the 412
      smears showing pathologic findings (mild to severe dysplasia or worse),
      diagnostic cells were present in 400 Cytobrush samples and in 369 spatula
      samples; the combination of both samples thus gave a 3% gain in correct diagnoses
      as compared to use of the Cytobrush samples alone. Another 18 smears would have
      been underdiagnosed based only on the Cytobrush samples. Endocervical cells were
      present in 95.3% of the Cytobrush samples and 83.8% of the spatula samples;
      squamous cells were present in 93.9% of the Cytobrush samples and 96.8% of the
      spatula samples. Analysis confirmed that it is important that the smear should
      contain both endocervical and squamous cells. A positive relationship between the
      absence of squamous cells in the Cytobrush sample and the probability of a false
      negative assessment was suggested. It thus seems inadvisable to replace the
      combination sampling method by Cytobrush sampling alone, which may lead to a
      false-negative diagnosis.

PMID- 1994638
TI  - Comparison of spatula and nonspatula methods for cervical sampling.
AB  - A comparison between nonspatula (cotton swab and Cytobrush) cervical sampling
      methods and spatula (wooden Ayre spatula and plastic extended-tip Szalay Cyto
      Spatula) sampling methods was made in 109 cases. Based on the presence of
      endocervical cells, there were statistically significant qualitative differences
      between the non-spatula methods as well as between the spatula methods, but not
      between the Cytobrush and Cyto-Spatula smears or the cotton swab and Ayre spatula
      smears. In all kinds of inflammatory lesions, the spatula samples were more
      accurate and diagnostic than the nonspatula ones. In all cases of cervical
      intraepithelial neoplasia and in most cases of squamous metaplasia, the Cyto
      Spatula sample was the most accurate. It is concluded that the Szalay Cyto
      Spatula method is superior to the other cervical sampling methods because it
      provides well-preserved cells from both the endocervix and the ectocervix in one
      smear. The Cytobrush should be used in conjunction with spatula sampling
      (combination method) for effective sampling of the cervix. The Cytobrush alone is
      effective mainly for endocervical sampling while the Ayre spatula alone is
      effective mainly for ectocervical sampling; the cotton swab is ineffective for
      both endocervical and ectocervical sampling.

PMID- 1994636
TI  - Exploiting the "toothpick effect" of the Cytobrush by plastic embedding of
      cervical samples.
AB  - The introduction of the combined spatula-Cytobrush sampling method has increased
      the diagnostic accuracy of cervical cytology. However, the smears from a small
      number of cases contained epithelial fragments dislodged by the "toothpick
      effect" of the Cytobrush. Due to their thickness, these epithelial fragments in
      the smears are very difficult (if not impossible) to scrutinize and are thus
      undiagnosable. The presence of only such fragments in smears led to false
      negative diagnoses in two cases of invasive carcinoma. To solve this problem,
      these epithelial fragments were embedded in plastic, with thin sections prepared
      from the blocks. This paper presents the morphologic features and diagnostic
      accuracy of 77 such problem cases (found among 50,000 cases with spatula
      Cytobrush smears) to which this method was applied. In almost all cases, the
      diagnosis on the plastic-embedded sections matched the diagnosis on the
      colposcopically directed biopsy. Of these 77 patients, the biopsy diagnosis
      showed 5 severe dysplasias, 6 carcinomas in situ, 1 squamous-cell carcinoma, 2
      adenocarcinomas in situ and 2 adenocarcinomas. In addition, data are presented
      concerning the nuclear-size and shape-factor differences in smears versus plastic
      embedded sections, and the stereologic consequences of smearing and cutting these
      epithelial fragments are discussed. These plastic-embedded sections are well
      suited for use in quantitative microscopy, as well as for diagnostic purposes.

PMID- 1994639
TI  - Cervical smears following laser treatment. Comparison of Cervex brush versus
      Cytobrush-Ayre spatula sampling.
AB  - For 802 women at initial follow-up after laser treatment of cervical lesions, 421
      smears prepared using the Cervex brush were compared with 381 smears prepared
      using the combination of a Cytobrush plus an Ayre spatula. The smears were graded
      for adequacy, the presence of endocervical or metaplastic cells and the presence
      and degree of epithelial abnormalities. Endocervical or metaplastic cells were
      seen more often in Cytobrush-Ayre spatula smears (94.5%) as compared with Cervex
      brush smears (88.8%; P = .004). Also, the number of samples classed as inadequate
      was significantly greater with Cervex brush smears (4.0%) than with Cytobrush
      Ayre spatula smears (0.3%; P = .0003). The number of smears showing dysplasia was
      too small to detect realistic differences between the two sampling methods. These
      findings suggest that, in women who have had laser treatment of the cervix,
      Cytobrush plus Ayre spatula sampling produces better-quality smears than does
      Cervex brush sampling, with regard to both adequacy and the presence of
      endocervical cells.

PMID- 1994640
TI  - Use of the Cytobrush for cervical sampling after cryotherapy.
AB  - The presence of endocervical cells in routine gynecologic smears (prepared from
      spatula and cotton swab samples) and Cytobrush smears was analyzed in 52 patients
      with a history of prior cryotherapy. These cases represented 11% of the 491 women
      evaluated using both techniques between August 1, 1987, and January 31, 1990. The
      routine smear contained endocervical cells in 25 (48%) of the 52 cases while the
      Cytobrush smear contained endocervical cells in 49 (94%) of the cases. The use of
      the Cytobrush for cervical cytologic screening thus appears to be of value in
      patients with a prior history of cryotherapy, which frequently renders the
      transformation zone less accessible to routine sampling.

PMID- 1994641
TI  - The validation of cervical cytology. Sensitivity, specificity and predictive
      values.
AB  - Statistics and methods for the validation of the results of cytologic screening
      for cervical cancer and its precursors were examined. Many of the methods
      commonly used, including the calculation of sensitivity and specificity on raw
      data, contain flaws that undermine their conclusions. Using a large computerized
      database of 748,871 cytologic screenings of 277,842 women over a ten-year period,
      the value of screening was examined. Only subsequent histologic examinations
      within one year were accepted to validate positive initial cytologic diagnoses;
      only two subsequent cytologic screenings within the next three years were
      accepted to validate negative initial cytologic diagnoses that had not been
      followed by a histologic examination. Cases not meeting these criteria were
      excluded from the initial analysis. From these data, the predictive value of a
      negative cytologic examination was determined to be 99.8%; the predictive value
      of a positive cytologic examination was 73.4% for an initial diagnosis of mild-to
      moderate dysplasia, 90.6% for a diagnosis of severe dysplasia/carcinoma in situ,
      94.5% for a diagnosis of carcinoma in situ or microinvasive carcinoma and 95.5%
      for an initial diagnosis of invasive carcinoma. Cases with an initial
      "questionable" cytologic diagnosis had a positive predictive value of only 64.0%.
      Extrapolation from the validated cases to the entire screened population showed
      an overall sensitivity of 80% and a specificity of 99.4% for cytologic screening
      for cervical cancer. The sensitivity was slightly lower for mild and moderate
      dysplasia (78.1%) and slightly higher for carcinoma in situ and severe dysplasia
      (81.4%) and invasive carcinoma (82.3%).

PMID- 1994642
TI  - Prevalence of psammoma bodies in Papanicolaou-stained cervicovaginal smears.
AB  - Reports from sequential series of 234,318 cervicovaginal smears from a period of
      three years were reviewed to ascertain the prevalence and significance of
      psammoma bodies. Seven smears contained psammoma bodies. Three of the seven were
      associated with benign conditions and four were associated with a cancer (two
      serous papillary endometrial adenocarcinomas, one ovarian serous
      cystadenocarcinoma and one serous papillary carcinoma of the peritoneum). The
      prevalence of psammoma bodies in benign cases was much higher than reported in
      previous studies, in which most findings of psammoma bodies were associated with
      malignancy, particularly ovarian carcinoma. A consistent and useful feature in
      distinguishing psammoma bodies associated with benign or malignant disease was
      the presence of a few adherent small bland-appearing glandular cells in benign
      disorders and adherent malignant glandular cells in cases of carcinoma. A more
      conservative work-up may be merited in young women with clearly benign cells
      associated with psamoma bodies in a cervicovaginal smear and an otherwise
      negative physical examination and noncontributory endometrial sampling.

PMID- 1994643
TI  - Significance of anucleated squames in Papanicolaou-stained cervicovaginal smears.
AB  - The significance of anucleated squames in Papanicolaou-stained cervicovaginal
      smears as a marker of hyperkeratosis with an underlying significant atypia was
      evaluated. Over a two-year period, 785 (0.47%) of 168,215 cervicovaginal smears
      were signed out as demonstrating anucleated squames without any other
      abnormality. Cytologic or histologic follow-up specimens were available for 304
      of those smears (42%). Histology or cytology showed condyloma or a more
      significant lesion in 13 cases (4.3%); histology showed hyperkeratosis without
      atypia in 25 cases (8.2%) and chronic cervicitis in 23 (7.5%); follow-up cytology
      demonstrated persistent anucleated squames in 47 cases (15.4%) and was negative
      in 196 (64.6%). During this same period, the rate of condyloma or a more
      significant lesion in all Papanicolaou smears examined was 1.69%. Thus, reporting
      the presence of anucleated squames in the absence of any other abnormality
      appears to be of marginal value as a screening procedure for predicting the
      existence of a significant lesion. Noting their presence in patients with a prior
      diagnosis of condyloma or dysplasia remains an important tool for detecting a
      persistent lesion. Lack of standardization among pathologists in the recognition
      of anucleated squames may partially explain the low predictive value of this
      finding: an informally conducted survey revealed a mean accuracy of 46% in the
      identification of true anucleated squames.

PMID- 1994644
TI  - Immunohistochemical localization of glutathione S-transferase in preneoplastic
      and neoplastic lesions of the human uterine cervix.
AB  - A mouse monoclonal antibody and a rabbit polyclonal antibody prepared against the
      placental form of the enzyme glutathione S-transferase (GST-pi) were used to
      immunohistochemically stain normal and neoplastic human uterine cervical tissues
      from 88 cases. Of 65 cases of preneoplastic squamous lesions and invasive
      carcinomas of the cervix, 94% stained with the monoclonal antibody and 100% with
      the polyclonal antibody. In the 23 benign tissues, staining of ectocervical
      squamous epithelium was generally not observed; however, areas of reserve-cell
      hyperplasia, immature squamous metaplasia and adjacent endocervical cells did
      show staining (68% with the monoclonal antibody and 95% with the polyclonal
      antibody). Many of the positive tissue types showed a variety of staining
      patterns and intensities. These findings do not support the concept that GST-pi
      staining can be used to distinguish preneoplastic lesions of the cervix from
      benign reactive or proliferative processes. These results are of interest in the
      investigation of cervical carcinogenesis since GST-pi may be involved in an early
      stage of neoplastic transformation of the cervical epithelium. The correlation of
      these findings with the results of human papillomavirus testing and DNA content
      analysis should be of interest in determining the relationship of this enzyme to
      cervical neoplasia.

PMID- 1994645
TI  - Philosophy, technical principles, selection, and indication in body contouring
      surgery.
AB  - The experiences of almost three decades of performing various types of body
      contouring surgery, in both pre- and postlipoplasty periods, using many different
      techniques are described. Contouring surgery for such body areas as the abdomen,
      flanks, inner and outer thighs, and buttocks is discussed in detail.

PMID- 1994646
TI  - The first pre- and post-operative photographs of plastic and reconstructive
      surgery: contributions of Gurdon Buck (1807-1877).

PMID- 1994647
TI  - Rhytidectomy: suprazygomatic and infrazygomatic SMAS treatment.
AB  - The soft tissues of the face and neck are firmer above the zygomatic arch than
      below it. The SMAS should be treated differently according to where it is
      situated with respect to this arch. Above the arch, both the skin and the S-SMAS
      are firmly attached making it possible to correct both simultaneously by means of
      a flap that includes both layers. Beneath the zygomatic arch correcting the I
      SMAS by stretching and relocating it enhances the contour of the jaw and neck and
      gives greater support to the skin. This provides for even better conformation
      when excess subcutaneous tissue is resected. An intermediate region exists
      between the corrected areas of the S-SMAS and the I-SMAS where the rhytidoplasty
      is exclusively performed through traction and rotation of the skin, but added
      resources diminish traction sequels.

PMID- 1994648
TI  - Correction of breast ptosis utilizing a "fold over" de-epithelialized lower
      thoracic fasciocutaneous flap.
AB  - In the operation described, vascularized dense connective tissues, consisting of
      two layers of dermis or fascia, are supplied from below the inframammary fold and
      shaped surgically into a supportive subcutaneous "cup." The reconstruction adds
      to the effect of the dermal mastopexy for the treatment of breast ptosis. This
      fasciocutaneous type of flap also augments the breast, and a pleasing projection
      may be achieved without resorting to an implant. The degree of augmentation
      depends upon the thickness of the subcutis donor site.

PMID- 1994649
TI  - Silicone gel granuloma following compressive mammography.
AB  - Silicone implant rupture is well recognized, particularly with the thin-walled
      implants inserted some years ago. On occasions a chronic granulomatous
      inflammation has been noted if silicone globules have infiltrated the tissues.
      The rupture may occur apparently spontaneously or after trauma, including
      attempts at external closed capsulotomy. The case report presented in this
      article documents rupture and dissemination of silicone caused by compressive
      mammography. Recent practice suggests that in order to enhance the image produced
      by mammography, particularly in the presence of the masking of a silicone
      implant, extreme compression is the preferred technique but perhaps should be
      regarded with some caution in patients with breast implants.

PMID- 1994650
TI  - Mandibular contouring surgery for purely aesthetic reasons.
AB  - The mandible's contour determines the shape of the lower part of the face and
      thus influences the appearance of the face and neck. There are two types of
      operative procedures that can be used on mandibular contour and they do not
      require orthodontic treatment: mandible angle reduction and genioplasty. We
      divided the mandible angle reduction group into Types A, B, and C according to
      the grade of angle protrusion. Type A needs just an angle resection, Type B needs
      an angle resection and resection of part of the body, and Type C needs resection
      of the angle, the body, and part of the symphysis. We have performed 258
      mandibular contouring procedures. In genioplasty, shaving, advancement,
      shortening, and lengthening generally can be employed. Furthermore, when vertical
      lengthening is used, ostectomized mandible angle bone is carved and then grafted
      between the horizontal osteotomy site. Of the mandible angle reduction cases, 21
      were Type A, 186 were Type B, and 28 were Type C. The curved ostectomy is most
      important in mandible angle reduction cases in order to achieve a more natural
      curve of the mandible's lower border. A total of 71 patients were very pleased
      with the results of the combined procedures of genioplasty and angle reduction.

PMID- 1994651
TI  - Nasolabial fold undermining and fat grafting based on histological study.
AB  - When treating nasolabial folds, it is necessary to radically undermine the
      adjacent tissues before using fat grafts or fat injections in order to place the
      fat in the proper locations and, thus, prevent placing it inside muscle tissue.
      The method described here avoids augmenting the volume of the adjacent lip and
      cheek tissues lateral to the nasolabial fold which can cause poor results.

PMID- 1994652
TI  - Obesity can be treated by suction lipoplasty when combined with other procedures.
AB  - The development of serial suction lipoplasty enables us to remove substantial
      amounts of subcutaneous fat safely and dependably on an outpatient basis, and
      free our patients of the worry of exogenous blood transfusion. Many practitioners
      and researchers do not advocate suction for the treatment of obesity, but rather
      regard it as a means of treating localized small deposits of fat or "figure
      faults." The reason for their caution is that the amounts of fat to be removed
      from the obese patient would require extensive hospitalization, transfusion, and
      increased risk of complications. Liposuction, when performed as a series, can
      make the treatment of obesity as safe as the treatment of smaller figure faults.
      We now use serial suction as an adjunct to other surgical and dietary methods for
      the control of obesity.

PMID- 1994654
TI  - A critical look at abdominal lipectomy following morbid obesity surgery.
AB  - This article reviews a series of 26 consecutive nonaesthetic post-morbid-obesity
      weight loss patients undergoing abdominal lipectomy. Patient satisfaction was
      assessed by a questionnaire. All patients obtained symptomatic relief but
      surprisingly most had expected to look better following surgery, indicating the
      importance of discussing this aspect preoperatively. Technical modifications to
      remedy some of these problems are discussed.

PMID- 1994653
TI  - Functional applications of suction-assisted lipectomy: a new treatment for old
      disorders.
AB  - Ever since the introduction of suction-assisted lipectomy in the United States in
      1981, the technique has been applied to an increasing number of disorders of the
      subcutaneous tissues. Indeed, suction-assisted lipectomy has evolved into the
      method of choice in the treatment of certain pathological entities. While the
      extraction of lipomas is the most common functional application, suction-assisted
      lipectomy has also been used successfully to treat such conditions as
      gynecomastia, axillary hyperhidrosis, benign symmetric lipomatosis (Madelung's
      disease), congenital body asymmetry, congenital or acquired lymphedema, flap
      defatting, traumatic or postoperative hematomas, and fat necrosis. We have
      successfully treated patients presenting with the above disorders. No morbidities
      or mortalities were encountered in our series of 18 patients. The final results
      were considered favorable by the majority of patients. Acceptance by the patients
      of this treatment modality was extremely high because of the smaller incisions
      required, the exactness in contouring, the simple and minimal postoperative care
      needed, and the ease with which the procedure can be repeated to refine the
      results. A comprehensive review of the literature is presented along with our own
      patient management and long-term results.

PMID- 1994655
TI  - Gluteoplasty: a ten-year report.
AB  - In 1979 the author published an article on torsoplasty which included plastic
      reconstruction and augmentation of the deformed gluteal region. Several cases are
      presented in this article which are follow-ups to the type of gluteoplasty
      described ten years ago. It was found that there was considerable postoperative
      improvement for the patient and satisfaction for the surgeon.

PMID- 1994657
TI  - Exercise echocardiography and technetium-99m MIBI single-photon emission computed
      tomography in the detection of coronary artery disease.
AB  - To compare the relative diagnostic value of exercise echocardiography with
      perfusion technetium-99m metoxyisobutylisonitrile single-photon emission computed
      tomography (SPECT) in detecting coronary artery disease (CAD), 75 patients with
      suspected CAD but a normal electrocardiogram (ECG) at rest were included in a
      prospective correlative study. Both the exercise echocardiograms and SPECT
      studies were performed in conjunction with the same symptom-limited bicycle
      exercise test. The development of either a new wall motion abnormality or a
      reversible perfusion defect after exercise, or both, were regarded as a positive
      test for the exercise echocardiographic and SPECT studies, respectively. The
      results of these 2 diagnostic tests were compared with coronary arteriography.
      Exercise echocardiography identified 35 (71%) and SPECT 41 (84%, p = 0.13) of the
      49 patients with significant CAD (defined as greater than 50% diameter stenosis).
      Twenty-five of the 26 patients (96%) without significant coronary stenosis had
      negative exercise echocardiographic results and 23 of 26 (88%) had negative SPECT
      results. Exercise-induced new wall motion abnormalities showed a good correlation
      with reversible perfusion defects, and the results of the 2 methods were
      concordant in 65 of 75 patients (agreement = 88%, kappa = 0.75 +/- 0.14). Both
      the diagnostic accuracy of exercise echocardiography and SPECT were significantly
      higher than the exercise ECG (81 vs 64%, p less than 0.02 and 88 vs 64%, p less
      than 0.005). The sensitivity and specificity for detecting individual diseased
      vessels were 60 and 95% for exercise echocardiography and 67 and 94% for
      SPECT.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1994656
TI  - Electrocardiographic subset analysis of diltiazem administration on long-term
      outcome after acute myocardial infarction. The Multicenter Diltiazem Post
      Infarction Trial Research Group.
AB  - The effect of diltiazem on long-term outcome after acute myocardial infarction
      (AMI) was assessed in 2,377 patients enrolled in the Multicenter Diltiazem Post
      Infarction Trial and subsequently followed for 25 +/- 8 months. The study
      population included 855 patients (36%) with at least 1 prior AMI before the index
      infarction and 1,522 patients (64%) with a first AMI, of whom 409 (27%) had a
      first non-Q-wave AMI, 664 (44%) a first inferior Q-wave AMI, and 449 (30%) a
      first anterior Q-wave AMI. This post hoc analysis revealed that, among patients
      with first non-Q-wave and first inferior Q-wave AMI, there were fewer cardiac
      events during follow-up in the diltiazem than in the placebo group, and that the
      reverse was true for patients with first anterior Q-wave AMI or prior infarction.
      The diltiazem:placebo Cox hazard ratio (95% confidence limits) for the trial
      primary end point (cardiac death or nonfatal reinfarction, whichever occurred
      first) was: first non-Q-wave AMI-0.48 (0.26, 0.89); first inferior Q-wave AMI
      0.66 (0.40, 1.09); first anterior Q-wave AMI-0.82 (0.51, 1.31); and prior AMI
      1.11 (0.85, 1.44). Use of cardiac death alone as an end point gave an even more
      sharply focused treatment difference: first non-Q-wave AMI-0.46 (0.18, 1.21);
      first inferior Q-wave AMI-0.53 (0.27, 1.06); first anterior Q-wave AMI-1.28
      (0.68, 2.40); prior infarction-1.26 (0.90, 1.77). Further analysis revealed that
      these differences in the effect of diltiazem in large part reflected the
      different status of the 4 electrocardiographically defined subsets in terms of
      left ventricular function.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1994659
TI  - The Dutch experience in percutaneous transluminal angioplasty of narrowed
      saphenous veins used for aortocoronary arterial bypass.
AB  - Of 19,994 percutaneous transluminal coronary angioplasty procedures performed in
      The Netherlands between April 1980 and January 1989, the long-term follow-up of
      454 patients who underwent angioplasty of greater than or equal to 1 saphenous
      vein bypass graft was reviewed. In 46% of patients single graft angioplasty was
      attempted, and in 54% of patients sequential graft angioplasty was attempted. The
      clinical primary success rate was 90%. In-hospital mortality was 0.7%, 2.8% of
      patients sustained a procedural myocardial infarction, and 1.3% of patients
      underwent emergency bypass surgery. After a follow-up period of 5 years, 74% of
      patients were alive, and 26% were alive and event-free (no myocardial infarction,
      no repeat bypass surgery or repeat angioplasty). In patients in whom the initial
      angioplasty attempt was unsuccessful, only 3% were event-free at 5 years, versus
      27% of successfully dilated patients. The time interval between the angioplasty
      attempt and previous surgery was a significant predictor for 5-year event-free
      survival. The event-free survival rates for patients who had bypass surgery 1
      year before, between 1 and 5 years, and 5 years before angioplasty, were 45, 25
      and 19%, respectively. Less than one-third of patients with previous bypass
      surgery who had angioplasty of the graft remained event-free after 5 years. In
      patients needing angioplasty within 1 year after bypass surgery, better long-term
      results were achieved.

PMID- 1994658
TI  - Impaired left ventricular filling and regional diastolic asynchrony at rest in
      coronary artery disease and relation to exercise-induced myocardial ischemia.
AB  - Impaired left ventricular (LV) diastolic filling at rest is frequently observed
      in patients with coronary artery disease (CAD) who have normal LV systolic
      function and no previous infarction. To test the hypothesis that abnormal
      diastolic function at rest might reflect the functional severity of CAD, as
      estimated by exercise-induced ischemia, the relation between regional and global
      LV diastolic function at rest and during exercise-induced ischemia was evaluated
      in 49 patients with radionuclide angiography. All patients had normal systolic
      function at rest. Group 1 (n = 26) patients manifested a normal ejection fraction
      response to exercise and group 2 (n = 23) patients an abnormal response. Data
      obtained from 22 age-comparable normal volunteers were used for comparison.
      Although regional and global diastolic function were not different between normal
      subjects and group 1 patients, peak filling rate was lower in group 2 patients
      than in normal subjects (2.5 +/- 0.8 vs 3.2 +/- 0.6 end-diastolic counts/s; p
      less than 0.01). Moreover, regional diastolic asynchrony, as assessed from the
      radionuclide data by using a regional sector analysis of the LV region of
      interest, was greater in group 2 patients (46 +/- 44 ms) than in both normal
      subjects (25 +/- 16 ms; p less than 0.05) and group 1 patients (23 +/- 16 ms; p
      less than 0.05). Thus, among patients with CAD and with normal LV systolic
      function at rest, impaired LV filling and regional asynchrony predict a greater
      degree of exercise-induced ischemia, suggesting a greater extent of jeopardized
      myocardium.

PMID- 1994660
TI  - Predictors of cardiac survival after percutaneous transluminal coronary
      angioplasty in patients with severe left ventricular dysfunction.
AB  - To assess the outcome of percutaneous transluminal coronary angioplasty (PTCA) in
      patients with severe left ventricular (LV) dysfunction and to determine the
      predictors of mortality, 73 patients with LV ejection fraction less than or equal
      to 40% who underwent initial PTCA were analyzed. The majority of patients had
      prior (greater than 1 week) myocardial infarction (62 patients, 85%). Congestive
      heart failure and unstable angina were present in 24 (45%) and 49 (67%) patients,
      respectively. Multivessel coronary artery disease was present in 60 (83%). The LV
      ejection fraction ranged from 14 to 40% (mean 34%). Intraaortic balloon pump
      (15%) and percutaneous cardiopulmonary bypass support (4%) was used infrequently.
      Angiographic success was obtained in 109 of 128 lesions (85%) attempted. Complete
      revascularization was obtained in 16 of 60 patients with clinical success.
      Procedure-related mortality was 5% (4 patients). All patients were followed from
      greater than or equal to 6 to less than or equal to 71 months (average 26). The
      estimated survival was 79 +/- 5%, 74 +/- 6%, 66 +/- 7% and 57 +/- 8% at 1, 2, 3
      and 4 years, respectively. A Cox regression analysis revealed that the presence
      of congestive heart failure, a lower LV ejection fraction and a higher myocardial
      jeopardy score for contractile myocardium were independent predictors of survival
      after PTCA in patients with LV dysfunction. In conclusion, a high-risk subset can
      be identified among patients with severe LV dysfunction who undergo PTCA.

PMID- 1994662
TI  - Sudden cardiac death while wearing a Holter monitor.
AB  - The Holter tapes of 61 patients (46 men, mean age +/- standard deviation 65 +/-
      11 years) with sudden cardiac death while being monitored were analyzed. Thirty
      eight patients were known to have coronary artery disease, 5 had cardiomyopathy,
      and 7 had aortic valve disease. Etiology remained unknown in 11 patients. Mean
      New York Heart Association functional class was 2.5 +/- 0.7. Thirty patients had
      received antiarrhythmic drugs and 32 had received digitalis. Sudden death
      occurred at rest in 73%. In the hours before death, repetitive ventricular
      arrhythmias were found in 50 patients (82%), with atrial fibrillation in 34%.
      Patients with bradyarrhythmic death (18%) had less complex ventricular activity
      compared to patients with tachyarrhythmic death (p less than 0.01). Lethal
      arrhythmias--monomorphic ventricular tachycardia, polymorphic ventricular
      tachycardia, torsades de pointes, primary ventricular fibrillation, and 1:1
      conducting atrial tachycardia--were found in 26 (43%), 15 (25%), 5 (8%), 3 (5%),
      and 1 patient, respectively. The coupling interval of the final ventricular
      tachycardia correlated inversely with the initial frequency of ventricular
      tachycardia (p less than 0.05). For patients with tachyarrhythmic death, an
      increase of heart rate within the last 3 hours was noted (83 vs 89 beats/min, p
      less than 0.05). Ventricular premature complexes and the proportion of patients
      with greater than 2 couplets and greater than 2 triplets increased significantly
      only within the last hour before death.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1994663
TI  - Late results of the left subcostal approach for automatic implantable
      cardioverter defibrillator implantation.
AB  - A left subcostal surgical approach was used to implant an automatic implantable
      cardioverter defibrillator (AICD) in 48 patients with a history of nonfatal
      cardiac arrest or documented ventricular tachycardia/fibrillation.
      Electrophysiologic studies before surgery yielded induction of monomorphic or
      polymorphic ventricular tachycardia in 40 patients, whereas 8 were noninducible.
      Mean (+/- standard deviation) age was 58 +/- 12 years. Mean ejection fraction was
      33 +/- 16%. Thirty patients (63%) had documented coronary artery disease; 14
      patients (29%) had previous coronary bypass surgery. The mean intraoperative
      defibrillation threshold was 13.8 +/- 6.6 J. In 6 patients, an adjunctive right
      minithoracotomy was used to position 1 patch over the right atrium and thus
      optimize the defibrillation threshold. Patients with prior exposure to amiodarone
      and previous coronary bypass surgery had higher defibrillation thresholds at
      implantation. Two perioperative deaths occurred. There were no infections. Long
      term follow-up yielded a 1- and 5-year survival of 0.88 and 0.58, respectively,
      and a freedom from sudden cardiac death of 1.0 and 0.97, respectively. The
      nonthoracotomy, left subcostal surgical approach is safe and effective, provides
      adequate defibrillation thresholds in most patients, and yields long-term
      survival comparable to other implantation techniques.

PMID- 1994661
TI  - Effects of diltiazem on complications and restenosis after coronary angioplasty.
AB  - A randomized, placebo-controlled, double-blinded trial was performed to evaluate
      the usefulness of empiric therapy with a calcium antagonist in patients who
      undergo coronary angioplasty. A total of 201 patients were randomized to placebo
      or to high-dose diltiazem (mean dose, 329 mg/day). Treatment began 24 hours
      before angioplasty. Restenosis was assessed by percent area stenosis as
      determined by quantitative angiographic techniques before, immediately and 1 year
      after angioplasty. All patients also received aspirin and dipyridamole before
      angioplasty. Heparin and verapamil were administered intravenously during the
      procedure. The 2 groups were similar with respect to age, extent of coronary
      artery disease, smoking history, and baseline lipid levels. Procedural
      complications, including death (1 vs 1), Q-wave infarction (0 vs 3), acute
      occlusion (5 vs 5) and focal spasm (0 vs 0), were not significantly different in
      the diltiazem and placebo patients, respectively. Freedom from all acute
      complications was noted in 85% of patients in both groups. One-year angiographic
      follow-up was obtained in 60% of patients. Restenosis rates were similar: 36% in
      the diltiazem group and 32% in the placebo group (p = 0.30). The incidence of
      late cardiac events (death, Q-wave myocardial infarction, recurrent angina or
      coronary bypass graft surgery) was similar in the 2 groups. Thus, diltiazem did
      not influence the overall restenosis rate or prevent late events after coronary
      angioplasty.

PMID- 1994664
TI  - Beneficial effect of atrial pacing in severe acute aortic regurgitation and role
      of M-mode echocardiography in determining the optimal pacing interval.
AB  - The effect of atrial pacing on cardiac performance was assessed in 11 men (aged
      20 to 64 years) with recent-onset severe aortic regurgitation (AR), all of whom
      had diastolic closure of the mitral valve on the echocardiogram. Thermodilution
      cardiac outputs were determined, and aortic, left ventricular and pulmonary
      arterial wedge pressures recorded. Once baseline recordings were completed, the
      pacing rate was increased by increments of 10 beats/min (70, 80, 90...) to a
      maximal rate of 140 beats/min. The optimal pacing interval, obtained from
      hemodynamic data, was defined as that at which the lowest filling pressure was
      associated with the highest cardiac index. This was then compared with a pacing
      interval derived from the R wave of the electrocardiogram to the diastolic mitral
      closing point on the M-mode echocardiogram. Such an interval would shorten
      diastole without affecting forward mitral flow. Atrial pacing improved the
      overall hemodynamic state in all patients; the most favorable hemodynamics were
      achieved at heart rates between 110 and 130 beats/min (mean: 120 +/- 8). At the
      optimal rate, left ventricular end-diastolic pressure decreased from 46 +/- 7 to
      23 +/- 12 mm Hg (p less than 0.001), and the pulmonary arterial wedge pressure
      from 28 +/- 8 to 16 +/- 7 mm Hg (p less than 0.001), while the cardiac index
      increased from 2.34 +/- 0.46 to 2.63 +/- 0.49 liters/min/m2 (p less than 0.01).
      The mean difference between the optimal pacing interval determined from the
      hemodynamic data and the interval derived from the echocardiogram was 18 +/- 21
      ms.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1994665
TI  - Simultaneous occurrence of mitral valve prolapse and systolic anterior motion in
      hypertrophic cardiomyopathy.
AB  - This report describes the simultaneous occurrence of mitral valve prolapse (MVP)
      and systolic anterior motion (SAM) in hypertrophic cardiomyopathy (HC). In 25
      patients (aged 7 to 62 years, mean 29), 15 (60%) of whom were male, distal
      portions of the anterior or posterior mitral leaflets approached or made
      midsystolic contact with the ventricular septum, whereas the proximal portion of
      the mitral leaflets showed marked cephalad excursion into the left atrium, 5 to
      15 mm beyond the mitral annular plane. Three mitral valves that were available
      for gross visual inspection were not morphologically typical of patients with
      primary MVP. Clinical features and natural history (1 to 14 years [mean 6] of
      follow-up), cardiac dimensions, and distribution of left ventricular hypertrophy
      defined in the study patients did not appear to differ distinctly from those in
      the overall referral population of patients with HC evaluated at our institution.
      Hence, patients with HC may show a striking pattern of mitral valvular motion
      involving SAM into the left ventricular outflow tract, as well as MVP; this
      prolapse motion is probably due to anatomic disproportion between the mitral
      valve and the small left ventricular cavity rather than to the coexistence of 2
      separate disease entities. Such patients further define the great diversity
      evident within the broad clinical spectrum of HC.

PMID- 1994666
TI  - Comparison of left ventricular ejection fraction by magnetic resonance imaging
      and radionuclide ventriculography in idiopathic dilated cardiomyopathy.
AB  - To assess the validity of gated magnetic resonance imaging (MRI) in determining
      left ventricular (LV) ejection fraction (EF), MRI (Spin Echo, multislice
      multiphase technique on the short-axis plane) was compared with equilibrium
      radionuclide ventriculography in 32 patients with idiopathic dilated
      cardiomyopathy. All patients underwent MRI and radionuclide ventriculography,
      performed consecutively on the same day (mean time interval between the 2
      examinations: 40 minutes). Comparison with LVEF showed a high correlation (y =
      0.79 X +3.51, r = 0.91; p less than 0.001). Mean difference between radionuclide
      ventriculography and MRI data was 1.7, with the 95% confidence interval 0.71 to
      2.68: MRI slightly underestimated LVEF. MRI interobserver and intrapatient
      variability (assessed in 15 of 32 patients) showed a high correlation (r = 0.91,
      r = 0.98). In conclusion, data suggest that MRI, using the short-axis approach
      and the multislice-multiphase technique, is an accurate, noninvasive, highly
      reproducible method of evaluating LVEF in patients with idiopathic dilated
      cardiomyopathy.

PMID- 1994667
TI  - Stroke volume during submaximal exercise in endurance-trained normotensive
      subjects and in untrained hypertensive subjects with beta blockade (propranolol
      and pindolol).
AB  - The effect of beta-adrenergic blockade on stroke volume (SV) at increasing
      submaximal exercise intensities was studied in 12 endurance-trained normotensive
      and 12 untrained hypertensive (diastolic blood pressure greater than 95 mm Hg)
      men, aged 18 to 34 years. Subjects were assigned to each of 3 treatments in a
      double-blind, randomized order: placebo, propranolol (80 mg twice daily) and
      pindolol (10 mg twice daily) for 10 days, with a period of 48 to 60 hours from
      the initial dose to the first treadmill test and a 4-day washout period between
      drugs. Cardiac output was measured using the carbon dioxide rebreathing method
      and SV was calculated from cardiac output and heart rate as follows: SV = cardiac
      output/heart rate. Cardiac outputs were estimated at rest and while walking on a
      treadmill at 25, 45, 60 and 75% of the subject's previously determined maximal
      oxygen uptake (VO2max). No significant differences were found in cardiac output
      between either of the drugs and placebo at rest, or at any of the 4 rates of
      work. Propranolol significantly increased SV above placebo values (p less than
      0.05) for both trained and untrained groups at the intensities of 45, 60 and 75%.
      Significant differences in SV were found between pindolol and placebo only at the
      intensities of 60 and 75% in the trained group. Contrary to expectations, SV
      showed no indication of a plateau with propranolol in the trained subjects
      throughout the 4 different exercise intensities, whereas a plateau was
      established under placebo conditions by 45% of VO2max in both trained and
      untrained subjects. These results suggest that both trained and untrained
      hypertensive persons can exercise with beta-adrenergic blockade at submaximal
      levels without compromised cardiac function.

PMID- 1994668
TI  - Epinephrine versus norepinephrine in prehospital ventricular fibrillation.

PMID- 1994669
TI  - Transcatheter laser-assisted balloon pulmonary valve dilation in pulmonic valve
      atresia.

PMID- 1994670
TI  - Atherectomy of right coronary ostial stenoses: initial and long-term results,
      technical features and histologic findings.

PMID- 1994671
TI  - Insights into the mechanism of luminal improvement after directional coronary
      atherectomy.

PMID- 1994672
TI  - Acute complications associated with new-onset atrial fibrillation.

PMID- 1994673
TI  - Time course of changes in pulmonary vascular resistance and the mechanism of
      regression of pulmonary arterial hypertension after balloon mitral valvuloplasty.

PMID- 1994674
TI  - Biologic intoxication due to digitalis-like substance after ingestion of cooked
      toad soup.

PMID- 1994675
TI  - Diagnosis of child sexual abuse in children with genital warts.

PMID- 1994676
TI  - Human immunodeficiency virus transmission by child sexual abuse.
AB  - During 1987-1989, 14 (14.6%) of the 96 children who tested positive for the human
      immunodeficiency virus (HIV) and were followed up by the Duke University (Durham,
      NC) pediatric acquired immunodeficiency syndrome team were confirmed to have been
      sexually abused. Every sexually abused child was evaluated for each of five modes
      of HIV transmission, and in nine children the pathway was identified. Four of the
      study children acquired HIV from child sexual abuse and in six, abuse was a
      possible source. Transmission by child sexual abuse was the most frequent of the
      proven modes of acquisition of HIV in this population. The other proven modes of
      acquisition were vertical transmission (n = 3) and HIV-contaminated blood
      transfusion (n = 2). Twelve males were identified (n = 8) or suspected (n = 4) of
      being perpetrators. Three knew themselves to have HIV at the time of an assault
      and eight were aware that the child had HIV at the time of an assault. There was
      no indication from any child that "safe sex" precautions had been observed.
      Children with HIV infection had multiple risk factors for abuse or neglect. The
      sociological descriptors of the lives of the 14 abused children showed multiple
      known risk factors for sexual abuse that also overlapped with known risk factors
      for or sequelae of the acquisition of HIV infection. These included drug abuse
      and alcoholism in the home, prostitution of a parent, lack of parenting, poverty,
      and chronic illness of the child. Prevention efforts should recognize that
      children as well as adults are at risk for sexually transmitted HIV infection.

PMID- 1994677
TI  - Sexual maturation and blood pressure levels of a biracial sample of girls.
AB  - A cross-sectional survey of 142 black and 361 white girls was performed to
      investigate whether differences in the timing of maturation account for blood
      pressure differences between same-aged subjects. Data were collected on blood
      pressure, anthropometric parameters, socioeconomic status, and secondary sex
      characteristics. Analysis of covariance was used to determine whether blood
      pressure for black and white girls differed significantly after adjusting for the
      confounding effects of different body size and sexual maturation distributions of
      the two groups. Advanced sexual maturation of the black girls contributed as much
      as the larger body sizes of the black girls to the blood pressure differences
      found between the black and white girls. Assessment of an individual's stage of
      sexual maturation at blood pressure measurement should be considered as important
      as the measurement of height and weight.

PMID- 1994678
TI  - Outpatient assessment of infants with bronchiolitis.
AB  - Two hundred thirteen infants younger than 13 months with bronchiolitis were
      prospectively followed up to identify the historical, physical, and laboratory
      clues at initial emergency department evaluation that would help to predict
      disease severity. Based on their total course of illness, the patients were
      classified as having mild (139 patients) or severe (74 patients) disease, and the
      initial emergency department evaluation findings of these two groups were
      compared. Six independent clinical and laboratory findings were identified that
      were strongly associated with more severe illness: (1) "ill" or "toxic" general
      appearance; (2) oxygen saturation less than 95%, as determined by pulse oximetry;
      (3) gestational age, younger than 34 weeks; (4) respiratory rate, 70/min or
      greater; (5) atelectasis on a chest roentgenogram; and (6) age, younger than 3
      months. The infant's oxygen saturation as determined by pulse oximetry was the
      single best objective predictor of more severe disease.

PMID- 1994679
TI  - Increased transient tachypnea of the newborn in infants of asthmatic mothers.
AB  - OBJECTIVE: To compare the incidence of transient tachypnea of the newborn (TTN)
      in infants of asthmatic vs nonasthmatic mothers. RESEARCH DESIGN: Case-control
      analysis. SETTING: Group model health maintenance organization. PATIENTS: A
      volunteer sample of 294 pregnant asthmatic women and 294 pregnant nonasthmatic
      women with normal pulmonary function test results, matched on the basis of age
      and smoking status. All subjects entered the study before their third trimester
      of pregnancy. Subjects with multiple gestations and abortions (less than 20
      weeks' gestation) were excluded. INTERVENTION: Asthma was treated in the allergy
      department. Routine obstetric, neonatal, and pediatric care was provided to all
      patients by staff physicians. MEASUREMENTS/RESULTS: Transient tachypnea occurred
      in 11 infants (3.7%) of asthmatic women and in one control infant (0.3%). There
      were no significant differences between asthmatic and matched control subjects in
      previously defined TTN risk factors, such as the occurrence of longer labors,
      failure to progress, cesarean sections, premature births, male sex, Apgar scores
      of less than 7 at 1 minute, or birth weight greater than 4 kg. Although infants
      of asthmatic mothers were more likely to exhibit wheezing by age 15 months
      compared with control infants (12.0% vs 3.2%), none of the infants with TTN
      manifested wheezing by age 15 months. No relationships could be identified in the
      asthmatic cohort between the occurrence of TTN and asthma severity or medication
      use (during the pregnancy in general or during labor and delivery in particular).
      CONCLUSION: Although the mechanism is uncertain, maternal asthma appears to
      increase the risk of infant TTN.

PMID- 1994681
TI  - Intraosseous infusion of dobutamine and isoproterenol.
AB  - Intraosseous infusion has been advocated as an emergency route in sick infants
      and children when intravenous access is not readily obtainable. Dobutamine
      hydrochloride and isoproterenol hydrochloride are useful emergency drugs that
      have not been studied when administered into the bone marrow. In a swine model,
      we compared the physiologic responses (heart rate, arterial pressure, and cardiac
      output) of dobutamine and isoproterenol infusions delivered intravenously and
      intraosseously during 20-minute intervals. We observed statistically significant
      effects of both dobutamine and isoproterenol delivered by the intraosseous route.
      In addition, the effects resulting from intraosseous infusion were statistically
      similar to those resulting from intravenous administration of these drugs. We
      conclude that the intraosseous infusion of dobutamine and isoproterenol is an
      effective and useful method for emergency administration of these medications.

PMID- 1994684
TI  - Tattooing behavior in adolescence. A comparison study.
AB  - We characterize associations with and motivations for tattooing in adolescents
      through data from a controlled, three-group comparison of adolescents from a
      substance abuse treatment program, detention center, and private pediatric
      practice. We surveyed 474 adolescents (12 to 18 years old) with tattoos (12%) and
      without tattoos (88%). The private pediatric practice was the control site. A 34
      item questionnaire was used to profile the three groups and their primary
      associations with tattooing with respect to race, drug use, school attendance,
      school grades, parental marital status, family income, tattooing by family
      members, criminal activity, and involvement with satanic rituals. Tattooing was
      significantly (P less than .005) associated with all of these variables in the
      ways described, as was knowledge of its association with human immunodeficiency
      virus infection. No interventions were made. Tattooing is common in adolescents
      and is associated with low self-esteem, delinquency, drug abuse, family and peer
      modeling, and participation in satanic rituals. Addressing the behavior as a
      health problem is discussed.

PMID- 1994683
TI  - Sudden cardiac death in young athletes. A review.

PMID- 1994682
TI  - Effectiveness of growth-promoting therapies. Comparison among growth hormone,
      clonidine, and levodopa.
AB  - The ability of growth hormone, clonidine, and levodopa to stimulate growth was
      compared in short and slowly growing children randomly assigned to different
      treatment regimens for 6 months. There were 10 children in each group, and 10
      additional subjects served as controls. Growth hormone improved mean height
      velocity, height velocity SD score, and height SD score. The mean height velocity
      and height velocity SD score were significantly increased by clonidine, while
      levodopa only enhanced the mean height velocity SD score of the treated children.
      Moreover, in nine patients (90%) receiving growth hormone, two (20%) receiving
      clonidine, and one (10%) receiving levodopa, the height velocity was raised by
      more than 2 cm/y. The increments in height velocity and height SD score were
      greatest in the growth hormone group. Clonidine induced an increase in height
      velocity significantly different from that in control children only. In the
      control group, there was a significant reduction of height SD score with time.

PMID- 1994685
TI  - Skateboarding injuries in children. A second wave.
AB  - Motivated by a number of skateboard-related injuries seen in an emergency
      department, we undertook an investigation of skateboarding injuries in the mid
      1980s. We studied US Consumer Product Safety Commission injury frequency
      estimates, which indicated a resurgence of these injuries: 19,182 in 1984 and
      37,180 in 1985. Children 10 to 14 years old were injured with greatest frequency.
      Nontrivial injuries were more common among children younger than 5 years old,
      reflecting a larger proportion of head and neck injuries. Boys sustained more
      frequent and more severe skateboard-related injuries. Observed injury patterns
      (head and neck injuries in younger children, extremity injuries in older
      children, and more severe head and neck injuries in older children) probably
      reflect the role of psychomotor development on both risk exposure and
      biomechanics. Likely prevention strategies include warnings against skateboard
      use by children younger than 5 years, prohibition of skateboards on streets and
      highways, and the promotion of use of helmets and other protective gear.

PMID- 1994686
TI  - Differences in infant mortality by race, nativity status, and other maternal
      characteristics.
AB  - The objective of this study was to examine the effects of nativity status (native
      vs foreign born) and other maternal characteristics (age, parity, education, and
      marital status) on infant, neonatal, and postneonatal mortality among white and
      black mothers. The design of this nonrandomized cohort study was based on birth
      and death certificates. The setting involved live births among US residents
      (excluding California, Texas, and Washington) in 1983 and 1984. The participants
      included white mothers with 4.4 million births and black mothers with 926,000
      births in single deliveries. There were no interventions. With regard to
      measurements (the main results), after adjusting for other risk factors, neonatal
      mortality risk was 22% lower among the black foreign-born mothers than among the
      black native-born mothers, while among white infants, there was no risk
      difference by nativity. Relative risks were more similar for postneonatal
      mortality, ie, 24% lower among black foreign-born mothers and 20% lower among
      white foreign-born mothers. Combining the several categories of risk factors into
      three broad maternal risk groups, there was a near-doubling of black and near
      tripling of white infant mortality rates between the low and high levels of
      maternal risk. We concluded that if the infant mortality rate in the low-risk
      groups could be achieved by the moderate- and high-risk groups, there would be a
      30% reduction in infant deaths within each race. Since the black infant mortality
      rate is twice the white infant mortality rate and black foreign-born mothers have
      much lower rates than black native-born mothers, it is likely that further
      improvement is possible among black infants.

PMID- 1994687
TI  - Retinopathy of prematurity in infants with cyanotic congenital heart disease.
AB  - We undertook a study of premature infants with cyanotic congenital heart disease
      to determine whether these infants develop retinopathy of prematurity despite a
      persistent hypoxemic state. Using the computerized registry of the neonatal
      intensive care unit of Vanderbilt University Medical Center, Nashville, Tenn, we
      identified six premature infants (less than 37 weeks' gestational age, with birth
      weights of 1100 to 2050 g) with cyanotic congenital heart disease who survived
      the neonatal period and underwent ophthalmologic evaluation. Review of their
      charts revealed that three of six infants developed retinopathy of prematurity
      (two had grade 1 and one had grade 3 disease), but none required treatment. Our
      data support the findings of other investigators that elevated arterial oxygen
      tension is not the sole factor leading to the development of retinopathy of
      prematurity. Premature infants with cyanotic congenital heart disease can develop
      retinopathy of prematurity despite persistent hypoxemia. Cyanotic premature
      infants should be screened for retinopathy of prematurity with the same
      thoroughness as other premature infants.

PMID- 1994688
TI  - Unsuspected cocaine exposure in young children.
AB  - OBJECTIVE: To determine the prevalence of cocaine exposure among preschool
      children with clinically unsuspected signs and/or symptoms. DESIGN: Prevalence
      study. SETTING: Pediatric emergency department in an inner-city hospital.
      PARTICIPANTS: 250 children aged 2 weeks to 5 years who underwent urine assays for
      cocaine prior to discharge from the emergency department. INTERVENTIONS: None.
      MEASUREMENTS/MAIN RESULTS: Six (2.4%) of the 250 urine assays (95% confidence
      interval, 0.5% to 4.3%) were positive for benzoylecgonine, the major urinary
      cocaine metabolite. Four of the positive urine assays were from children younger
      than 1 year and all children with positive urine assays were younger than 24
      months. None of these children presented with a complaint or was identified as
      having clinical problems currently associated with childhood exposure to cocaine.
      Possible exposure routes include breastfeeding, intentional administration,
      accidental ingestion of cocaine or cocaine-contaminated household dust via normal
      hand-to-mouth activity, and passive inhalation of "crack" vapors. CONCLUSION:
      Among the inner-city children served by this hospital, significant numbers of
      infants and young children are being exposed to cocaine, and this exposure occurs
      in a clinically unsuspected population.

PMID- 1994689
TI  - Radiological case of the month. Cavitary pneumonia due to Arcanobacterium
      hemolytic.

PMID- 1994690
TI  - Picture of the month. Acrodermatitis enteropathica.

PMID- 1994691
TI  - Late cholangitis after successful surgical repair of biliary atresia.
AB  - Bacterial cholangitis is a frequent complication of successful surgical repair of
      biliary atresia, occurring in 93% of patients before the age of 1 year, but
      thought to be rare after 2 years of age. Among 76 children free of jaundice more
      than 5 years after operation, four presented with late cholangitis (7 to 13.5
      years old), consisting of fever, jaundice, and abdominal pain with biochemical
      features of an inflammatory process and cholestasis. Liver biopsy specimens
      consistently demonstrated histological features of cholangitis, growth of
      microorganism, or both. Cholangitis subsided spontaneously in one patient or in
      response to intravenous administration of antibiotics. Cholangiography
      consistently demonstrated biliary abnormalities but no definite obstruction to
      the bilioenteric anastomosis. All the children had good hepatic function 3 weeks
      to 4 years after the episode of cholangitis. These results suggest that
      cholangitis may occur several years after surgery but does not seem to alter
      prognosis.

PMID- 1994692
TI  - Factors affecting outcome in meningococcal infections.
AB  - A prognostic score for evaluating meningococcal infections in patients consists
      of the following five features that indicate a poor prognosis: onset of petechiae
      within 12 hours of presentation; shock; normal or low peripheral leukocyte count;
      normal or low erythrocyte sedimentation rate; and absence of meningitis. Based on
      our experience and some published data, we suspected that the score may no longer
      be reliable. We reviewed the charts of 73 children with meningococcal infection
      from December 19, 1979 to December 19, 1987 and applied the prognostic score
      mentioned previously. Our findings indicate that although a low score is
      generally associated with a good outcome, a higher score is less predictive of
      poor outcome than previously suggested. A rash with petechiae or purpura, the
      presence of shock, and a normal or low peripheral leukocyte count continue to be
      predictors of poor outcome. Erythrocyte sedimentation rate was not evaluated
      owing to a limited amount of data. The absence of meningitis did not correlate
      with a worse outcome in our patients. Most patients who died had evidence of
      meningeal involvement at the time of presentation. Instead, altered mental status
      at presentation, particularly obtundation or coma, was an ominous sign. We
      conclude that absence of meningitis is not a good predictor of outcome, as was
      previously thought. Altered mental status at the time of presentation may prove
      to be a stronger indicator of poor outcome.

PMID- 1994693
TI  - Antibody responses to four Haemophilus influenzae type b conjugate vaccines.
AB  - Serum antibody responses to four Haemophilus influenzae type b capsular
      polysaccharide-protein conjugate vaccines (PRP-D, HbOC, C7p, and PRP-T) were
      studied and compared in 175 infants, 85 adults and 140 2-year-old children.
      Antibodies to the H influenzae type b polysaccharide vaccines were determined
      with a Farr-type radioimmunoassay. The infants received two doses of vaccine at
      the ages of 4 and 6 months. After the first dose of vaccine, the geometric mean
      antibody concentration measured at the age of 6 months was 0.09 to 0.10 mg/L,
      only marginally higher than that measured before immunization in all infants who
      had received PRP-D, HbOC, or C7p but increased to 0.82 mg/L in those who had
      received PRP-T. One month after the second dose, the geometric mean antibody
      concentration was increased in all vaccine groups. No significant differences
      were noted between recipients of HbOC, C7p, or PRP-T (geometric mean antibody
      concentrations, 4.32, 3.10, and 6.10 mg/L, respectively), whereas the PRP-D
      recipients had a significantly lower geometric mean antibody concentration (0.63
      mg/L). In contrast, PRP-D, HbOC, C7p, and PRP-T were all highly immunogenic in
      adults, with no differences noted among them. The 2-year-old children also
      responded to one dose of these vaccines with a high antibody concentration.

PMID- 1994694
TI  - Focal scleroderma and severe cardiomyopathy. Patient report and brief review.
AB  - A 21-month-old infant presented with simultaneous localized scleroderma and
      severe cardiomyopathy with heart failure. Cardiac abnormalities and serological
      changes (positive rheumatoid factor assay, elevated IgM and IgG levels, and
      elevated erythrocyte sedimentation rate) reverted to normal with prednisone
      therapy, and there was substantial, though incomplete, resolution of her skin
      changes during the same period. To our knowledge, this is the first patient with
      definite, clinically significant cardiac involvement associated with focal
      scleroderma. The possibility of internal organ involvement, including cardiac
      involvement, must be considered with focal scleroderma as well as with
      progressive systemic sclerosis.

PMID- 1994695
TI  - Chronic neutropenia during childhood. A 13-year experience in a single
      institution.
AB  - To evaluate the clinical course and characteristics of children with chronic
      neutropenia, we reviewed the charts of all such patients seen at our center
      during a 13-year period. A total of 50 patients with chronic neutropenia were
      identified. Three patients had documented congenital neutropenia, and two
      siblings had cyclic neutropenia. The remaining 45 children had chronic
      neutropenia of unknown origin. All children except two had a remarkably benign
      course despite markedly reduced granulocyte counts. Of six girls in this group
      who had abscess or cellulitis of the labia majora, it was a presenting
      manifestation in three. Resolution of neutropenia was documented in 23 (62%) of
      37 patients for whom follow-up information was available, with a median duration
      of neutropenia of 19 months. No differences were evident between patients with
      positive antineutrophil antibody test results and those in whom the test yielded
      negative results or was not performed. Chronic neutropenia in childhood is a
      relatively uncommon entity, characterized by a benign course and eventual
      resolution in the majority of patients.

PMID- 1994697
TI  - New effects of active and passive smoking on reproduction?

PMID- 1994696
TI  - Tobacco smoke exposure and pregnancy outcome among working women. A prospective
      study at prenatal care centers in Orebro County, Sweden.
AB  - Among 4,687 women undergoing prenatal care in Orebro County, Sweden, from October
      1980 to June 1983, 678 nonsmokers reported passive exposure to tobacco smoke. Of
      these women, 267 had been passively exposed at work, and the risk ratio (RR) for
      intrauterine death (spontaneous abortion or stillbirth) among these pregnancies
      was increased to 1.53 (95% confidence interval (CI) 0.98-2.38) compared with
      pregnancies of unexposed working women. This could not be explained by age,
      previous spontaneous abortion, educational level, planning of pregnancy, or
      alcohol use. The effect was confined to first-trimester fetal loss (adjusted RR =
      2.16, 95% CI 1.23-3.81), while active smoking was associated with intrauterine
      death after the first trimester. Passive exposure in the workplace was weakly
      associated with preterm birth (less than 37 weeks) but not with low birth weight
      (less than 2,500 g) among full-term livebirths. Active smoking clearly increased
      the risk of both of these outcomes. However, passive exposure in the home only
      did not seem to affect pregnancy outcome. The lack of quantitative exposure data
      points to the need for more research before passive exposure to tobacco smoke can
      be regarded as an established hazard to fetal development and survival.

PMID- 1994698
TI  - Occupational lead exposure and strabismus in offspring: a case-control study.
AB  - The authors conducted a population-based case-control study to investigate the
      association between strabismus and parental occupational lead exposure. Cases
      were children diagnosed with nonrestrictive strabismus between 1985 and 1986 at
      Baltimore, Maryland-area pediatric ophthalmology practices and clinics (n = 377).
      Controls were matched for age and hospital of birth (n = 377). Jobs held by
      parents were assessed for lead exposure by industrial hygienists. The time window
      for lead exposure was defined as the period from conception through age 9 months.
      The unadjusted odds ratio for maternal lead exposure and the esotropic form of
      strabismus was 2.6 (95% confidence interval (CI) 0.4-27). Unadjusted odds ratios
      for paternal occupational lead exposure and esotropia were 1.0 (95% CI 0.5-2.1)
      for low exposure, 2.1 (95% CI 0.9-5.3) for moderate exposure, and 1.2 (95% CI 0.4
      3.3) for high exposure. The study results suggest the possibility of a weak
      association between paternal lead exposure and strabismus in offspring.

PMID- 1994699
TI  - An adenomatous polyp case-control study to assess occupational risk factors
      following a workplace colorectal cancer cluster.
AB  - To assess potential etiologic factors among a population of Texas polypropylene
      workers previously found to have an excess of colorectal cancer (concentrated
      among mechanical and process workers), the authors conducted an adenomatous polyp
      case-control study. Cases (n = 24) were workers found to have adenomatous polyps
      during a company-sponsored colorectal cancer screening program, while controls (n
      = 72) were workers found to be free of polyps. Exposure assessment utilized a
      thorough industrial hygiene and toxicologic review of operations in conjunction
      with work activity interviews of cases and controls to develop chemical-specific
      exposure scores weighted by time, exposure level, and frequency of exposure.
      Stratified analyses and logistic regression found that cases tended to have
      higher exposure to pre-extrusion polymer plus additives (odds ratio (OR) = 2.6,
      90% confidence interval (CI) 1.1-6.3) and higher exposure to certain finishing
      additives (OR = 4.8, 90% CI 1.5-15.3). Analyses by job category or area of the
      plant did not indicate additional risk factors. The exposures identified in this
      study are discussed in light of the available toxicologic data on these and
      related compounds. The need for confirmatory experimental and epidemiologic
      studies is noted.

PMID- 1994700
TI  - Is vaginal douching related to cervical carcinoma?
AB  - The association between cervical carcinoma and vaginal douching was examined in a
      population-based case-control study conducted in the low-risk population of Utah
      between 1984 and 1987. The authors compared 266 cases of in situ and invasive
      cervical carcinoma with 408 group-matched controls by vaginal douching behavior,
      controlled for age, lifetime number of sex partners, cigarette smoking history,
      religious activity, and educational level. Essentially no association was found
      in women who douched once per week or less, but in those who douched more than
      once per week, a consistent relation was demonstrated (adjusted odds ratio = 4.7,
      95% confidence interval 1.9-11). Few differences were found with type of douching
      preparation used. The authors hypothesize that frequent douching alters the
      vaginal chemical environment, making the cervix more susceptible to pathologic
      change.

PMID- 1994701
TI  - The leukocyte count and cancer mortality.
AB  - A previous report that the leukocyte count was related to mortality from cancer
      was evaluated in two large groups of multiphasic health examinees in the San
      Francisco Bay area, California--a cohort of about 25,000 persons followed up for
      mortality and a cohort of about 160,000 persons followed up for cancer incidence
      between 1964 and 1980. The leukocyte count was related to mortality from all
      cancers, smoking-related cancers, and cancers that were not smoking-related, but
      it was not related to cancer mortality in nonsmokers. The leukocyte count showed
      an association with the incidence of smoking-related cancers that was only
      partially removed by analytical control for smoking. It was only slightly, if at
      all, related to the incidence of not-smoking-related cancers and to the incidence
      of all cancers among nonsmokers. The relation of the leukocyte count to cancer
      mortality appears to be due to its close association with cigarette smoking,
      which raises the incidence of certain cancers and can hasten death attributed to
      cancer.

PMID- 1994702
TI  - The epidemiology of diabetes complications study. IV. Correlates of diabetic
      background and proliferative retinopathy.
AB  - The roles of potential risk factors for background and proliferative retinopathy
      were evaluated in cross-sectional analyses from the Epidemiology of Diabetes
      Complications Study, Pittsburgh, Pennsylvania. This report presents results from
      the 657 insulin-dependent diabetic participants seen at the baseline examination
      (1986-1988). The presence of and severity of retinopathy were judged from
      stereoscopic photographs of three views of the ocular fundus using the modified
      Airlie House classification system. Fifty-three percent of the participants had
      background retinopathy, and 31% had proliferative retinopathy. Logistic
      regression analyses showed that among participants aged less than 18 years, those
      with background retinopathy were older and had higher levels of glycosylated
      hemoglobin compared with those without retinopathy. In the 18-29-year age group,
      participants with background retinopathy had a longer duration of diabetes,
      higher low density lipoprotein (LDL) cholesterol levels, and lower high density
      lipoprotein cholesterol levels and were more likely to have microalbuminuria
      compared with those without retinopathy. Participants aged 18-29 years with
      proliferative retinopathy had a longer duration of diabetes, higher diastolic
      blood pressure, and higher fibrinogen and LDL cholesterol levels than those with
      background retinopathy. In the age group greater than or equal to 30 years,
      diabetes duration, diastolic blood pressure, and fibrinogen, LDL cholesterol, and
      triglyceride levels were increased in participants with proliferative retinopathy
      versus those with background retinopathy. In a multivariate model of
      proliferative retinopathy, controlling for concurrent renal disease weakened the
      influence of blood pressure, fibrinogen, triglycerides, and LDL cholesterol and
      improved the overall fit of the model. These results suggest that diabetic
      nephropathy may contribute to the development of proliferative (but not
      background) retinopathy by increasing blood pressure and fibrinogen, by altering
      the lipoprotein profile, and possibly through other mechanisms.

PMID- 1994703
TI  - Acute giardiasis: an improved clinical case definition for epidemiologic studies.
AB  - In June 1983, an outbreak of waterborne giardiasis occurred in a group of 93
      university students and faculty participating in a geology field course in
      Colorado. All cases occurred in one subgroup of persons who were heavily exposed
      to untreated stream water on a field trip, and the risk of illness was strongly
      related to the amount of untreated stream water consumed. The median incubation
      period from a brief exposure to the first symptom was 7 days. The authors
      compared symptoms and stool sample results among 31 Giardia-positive persons in
      the exposed group and 36 Giardia-negative participants in an unexposed group to
      assess several case definitions for acute giardiasis. Diarrhea, abdominal cramps,
      flatulence, foul-smelling stools, nausea, excessive tiredness, bloating,
      anorexia, and chills were each significantly more common in the first group than
      in the second. A giardiasis case definition of 5 days or more of diarrhea--the
      definition used in many epidemiologic studies of giardiasis--had a specificity of
      100 percent but a sensitivity of only 32.2 percent compared with a definition
      based on results of stool examinations. When a case was defined as an illness
      lasting 7 days or more, with a combination of two or more of six symptoms
      (diarrhea, flatulence, foul-smelling stools, nausea, abdominal cramps, and
      excessive tiredness), sensitivity rose to 73 percent, with a specificity of 88
      percent. Such a case definition may be an improvement over that of 5 days of
      diarrhea, especially in outbreaks where there is good laboratory documentation
      that Giardia is the etiologic agent. The definition should be validated in other
      outbreaks and in situations where giardiasis must be distinguished from
      gastrointestinal disease caused by other agents.

PMID- 1994704
TI  - Re: "Agreement between questionnaire data and medical records: the evidence for
      accuracy of recall".

PMID- 1994705
TI  - Re: "The effects of sensitivity and specificity of case selection on validity,
      sample size, precision, and power in hospital-based case-control studies".

PMID- 1994706
TI  - Re: "Stature and the risk of myocardial infarction in women".

PMID- 1994707
TI  - Re: "Increased postperinatal child mortality among children of mothers exposed to
      measles during pregnancy".

PMID- 1994708
TI  - Re: "Be kind to your reader".

PMID- 1994709
TI  - Hypertension, endothelium, and cardiovascular risk factors.
AB  - The functions of the endothelium and the effects of hypertension,
      atherosclerosis, and diabetes on the endothelium are reviewed. The endothelium
      affects vascular tone by releasing vasodilators and modulating the effects of
      vasoactive substances such as catecholamines, bradykinin, serotonin, and
      angiotensin II. Relaxation of vascular smooth muscle depends upon a functionally
      intact endothelium and the release of the endothelium-derived relaxing factor
      nitric oxide. Endothelial cells also appear to release a hyperpolarizing factor
      that relaxes smooth muscle through activation of the sodium-potassium pump, and
      of the endothelium-dependent contracting factors. Similarities are found in the
      vascular injury resulting from hypertension, atherosclerosis, and diabetes. When
      these risk factors coexist, they can act synergistically and magnify the vascular
      injury. The endothelium appears to be one of the major targets for these forms of
      injury. Future therapeutic strategies will focus on ways to prevent, arrest, or
      reverse endothelial injury.

PMID- 1994710
TI  - Cardiovascular risk reduction: the role of antihypertensive treatment.
AB  - The effects of antihypertensive drugs on mortality from stroke, coronary artery
      disease (CAD), and nonvascular causes have been studied in 14 trials involving
      more than 37,000 patients. In the treated patients, blood pressure was 5 to 6 mm
      Hg lower than that in placebo-treated patients, and whereas mortality from stroke
      was reduced by 42%, CAD mortality was reduced by only 14%. A major reason for
      this lack of effect on CAD mortality is apparently the adverse effects of the
      primary drugs used in these trials (diuretics and beta blockers) on glucose
      tolerance, lipid levels, and insulin resistance. The angiotensin-converting
      enzyme inhibitors favorably influence many CAD risk factors, and their use can be
      expected to reduce CAD mortality in patients treated for hypertension.

PMID- 1994711
TI  - Workshop I--Fifth Joint National Committee report: how should it differ from the
      1988 report?

PMID- 1994712
TI  - Workshop III--Insulin resistance: is it truly the link?

PMID- 1994713
TI  - The National Cholesterol Education Program: guidelines, status, and issues.
AB  - The 1987 report of the Adult Treatment Panel (ATP) of the National Cholesterol
      Education Program (NCEP) was concerned with who should be treated for high blood
      cholesterol levels and how they should be treated. Total cholesterol levels were
      classified for identification of cases. Low-density lipoprotein cholesterol
      levels were classified for decisions about treatment. The ATP guidelines
      emphasize diet as the primary approach to treating patients with high blood
      cholesterol levels. The recommendations of the report are being widely publicized
      through physician and patient educational programs and the mass media. The report
      of the Population Panel of the NCEP provides recommendations and guidelines for
      the public health approach to the problem of high cholesterol levels. When the
      recommendations of both reports are fully implemented, it is expected that
      substantial reductions in the incidence of coronary heart disease will be
      achieved.

PMID- 1994714
TI  - The tangled web of coronary risk factors.
AB  - Although epidemiologic, genetic, and pathophysiologic studies have shown that low
      density lipoproteins (LDLs) are involved in the development of coronary artery
      disease, the standard measurement of LDL cholesterol comprises a number of
      separate components that may contribute in different ways to the disease process.
      Some of these components appear to be of particular pathologic importance.
      Intermediate-density lipoproteins (IDLs) and lipoprotein (a) are highly
      atherogenic species that each normally account for up to 10% to 15% total LDL
      cholesterol but may be disproportionately elevated in pathologic states and may
      therefore contribute disproportionately to coronary disease risk in certain
      patients. Recently, another subclass of LDL, characterized by relatively small
      particle size and increased density, also has been found to be associated with
      relatively increased risk of coronary disease. Furthermore, levels of this
      subclass, designated LDL-III, are linked to a number of interrelated hormonal and
      metabolic factors, each of which have also been associated with risk of coronary
      artery disease. These include male gender, postmenopause, abdominal adiposity,
      elevated triglyceride levels, increased levels of apolipoprotein B, and
      reductions in high-density lipoproteins (HDLs), particularly in the HDL2
      subclass. Other studies have demonstrated that many of these factors are also
      commonly associated with relative insulin resistance and hyperinsulinemia. Thus,
      a lipoprotein profile characterized by a relative increase in LDL-III and a
      reduction in HDL2 is indicative of a constellation of metabolic features that
      defines a high-risk state and that makes it extremely difficult to single out one
      or more factors that are most directly involved in the disease process.
      Combinations of genetic and environmental factors acting on this "tangled web" of
      risk factors may account for much of the variation in coronary disease
      susceptibility found in the general population.

PMID- 1994716
TI  - Workshop IV--National Cholesterol Education Program guidelines: are they
      clinically relevant?

PMID- 1994715
TI  - Regression of atherosclerosis: what does it mean?
AB  - Angiographic evidence of coronary artery atherosclerosis regression has been
      demonstrated in controlled clinical trials. The significance of this regression
      appears to depend in a complex way on the degree of atherosclerosis present when
      a regression regimen is initiated. Angiographic trials indicate that lesion
      change is a continuum, with a gradual transition from progression to stability
      and regression. Divergent lesion change can be seen in the same patient with a
      progression of some lesions and a regression of others. This makes it necessary
      to perform a comprehensive survey of all visible coronary segments when
      evaluating angiograms to determine the outcome of a clinical trial. An important
      finding in clinical trials is that new lesion formation can be reduced. This
      indicates that effective control of atherosclerosis may be possible with
      procedures now available, but noninvasive coronary artery imaging methods need to
      be refined.

PMID- 1994717
TI  - Workshop V--What is a risk factor and what is not--theoretical and practical
      implications.

PMID- 1994718
TI  - Workshop VI--Regression of atherosclerosis: what does it mean?

PMID- 1994719
TI  - Evolving natural history of coronary artery disease in diabetes mellitus.
AB  - White diabetic patients are at high risk of developing coronary artery disease
      (CAD). The natural history of CAD in insulin-dependent (ID) and noninsulin
      dependent (NID) diabetes mellitus (DM) is reviewed to gain insight into the
      mechanisms responsible for the development of premature or accelerated
      atherosclerosis in diabetic patients. In both IDDM and NIDDM, the risk of CAD
      increases with lengthening duration of diabetes; the risk, however, does not grow
      as a constant multiple of the nondiabetic risk of CAD, suggesting that the
      cumulative exposure to diabetes plays a significant role as a risk factor for CAD
      only in a subset of patients. This is consistent with the hypothesis that the
      diabetic milieu has an impact on the progression of atherosclerotic lesions but
      not on their initiation. This hypothesis is corroborated further by the
      observation that CAD does not occur in diabetic patients in populations with a
      low risk of CAD among nondiabetic patients. The component of the diabetic milieu
      responsible for promotion of atherosclerotic lesions is unknown. There is
      evidence, however, of a direct or indirect role of hyperinsulinemia in this
      process.

PMID- 1994720
TI  - Insulin as a mitogenic factor: role in the pathogenesis of cardiovascular
      disease.
AB  - Evidence has been accumulating that insulin has actions that may promote the
      development of atherosclerosis. Research has involved three broad areas: actions
      of insulin on cultured arterial cells, the effect of insulin on isolated artery
      preparations, and the development of lipid-containing lesions in the arteries of
      experimental animals. Insulin, in concentrations similar to those found in
      physiologic conditions, stimulates proliferation of cultured arterial smooth
      muscle cells from a number of species, including humans. Insulin also stimulates
      migration of smooth muscle cells. Cholesterol synthesis and low-density
      lipoprotein interaction with its receptor in smooth muscle cells are stimulated
      by insulin. Insulin's mitogenic action appears to be mediated by the insulin-like
      growth factor receptor. Endothelial cells cultured from large vessels are
      resistant to the actions of insulin, but hyperglycemia inhibits their
      proliferation. Insulin deficiency protects animals from experimental
      atherosclerosis; this protection is lost with insulin treatment. Insulin
      administration results in lipid-containing lesions in chickens and rats fed a
      normal diet, and in increased lipid synthesis in the arteries of pigs and dogs.
      Isolated artery preparations from insulin-deficient or insulin-treated animals
      undergo lipid metabolism at a rate that correlates with the insulin
      concentrations in the donor animals. The biological actions of insulin (and
      glucose) on arterial tissue suggest that hyperglycemia and hyperinsulinemia may
      promote the development of atherosclerosis.

PMID- 1994721
TI  - Diabetic retinopathy: can we modify its course?
AB  - With the exception of panretinal laser photocoagulation, no therapy has been
      shown to modify the course of diabetic retinopathy. Success in developing new
      therapies for diabetic retinopathy will depend on how well the disease process is
      understood and on whether interventions can be identified that ameliorate or
      circumvent critical stages in the development of the disease. A model of the
      disease process is presented to serve as a frame-work on which pieces of the
      puzzle can be placed and new areas of potential interventional therapy can be
      conceptualized.

PMID- 1994722
TI  - Insulin resistance, hyperinsulinemia, and hypertriglyceridemia in the etiology
      and clinical course of hypertension.
AB  - Patients with untreated hypertension have been shown to be resistant to insulin
      stimulated glucose uptake and are more hyperinsulinemic and hypertriglyceridemic
      than matched groups of patients with normal blood pressure. In addition, insulin
      resistance, hyperinsulinemia, and hypertriglyceridemia have been demonstrated in
      spontaneous hypertensive rats and in Sprague-Dawley rats fed a fructose-enriched
      diet. The defect in insulin-stimulated glucose uptake in these experimental
      models can also be shown at the cellular level. Experimental interventions that
      prevent insulin resistance or hyperinsulinemia from developing in fructose-fed
      rats also greatly attenuate the increase in blood pressure. Since endogenous
      hyperinsulinemia and hypertriglyceridemia have been identified as factors that
      increase the risk of coronary artery disease (CAD), it is likely that they
      contribute to the increased prevalence of CAD in hypertensive patients.
      Antihypertensive treatment may have exacerbated these metabolic abnormalities,
      which could help explain why it has been difficult to show that lowering blood
      pressure decreases the risk of CAD. These observations raise the possibility that
      abnormalities of carbohydrate and lipoprotein metabolism may play a role in both
      the etiology and clinical course of hypertension.

PMID- 1994724
TI  - Workshop VII--Patient population and genetics: role in diabetes.

PMID- 1994723
TI  - Diabetic nephropathy: can the natural history be modified?
AB  - Those diabetic patients who progress to advanced kidney disease constitute a
      subpopulation that is particularly vulnerable to the angiotoxic effects of the
      insulin-dependent disorder. Until the predisposing factors are identified, the
      most effective way to arrest renal deterioration is by controlling those
      currently recognized risk factors that accelerate the glomerulopathy. Treatments
      that normalize blood pressure, reduce dietary protein intake, and control
      hyperglycemia have been shown to retard the progression of diabetic nephropathy.

PMID- 1994725
TI  - Workshop VIII--Retinopathy, nephropathy, neuropathy, and tight control.

PMID- 1994726
TI  - Workshop IX--Lipids, insulin, diabetes.

PMID- 1994728
TI  - A history of phlebotomy therapy for hemochromatosis.
AB  - Hemochromatosis was recognized as an iron-storage disease for 50 years before it
      was proposed to treat it by removing hemoglobin. Davis and Arrowsmith are
      credited with the first report that demonstrated its value. Larger series have
      provided statistically valid evidence of improved quality of life and increased
      longevity. The earlier the disease is discovered, the less risk of morbidity and
      mortality. Screening tests (serum iron, total iron-binding capacity, serum
      ferritin) are recommended for all blood relatives of index cases of this
      hereditary disease and for all clinics where complications of hemochromatosis may
      be treated: liver disorder however mild, diabetes mellitus, heart disease,
      arthropathies, sterility, impotence, premature menopause, and abnormal
      pigmentation of the skin.

PMID- 1994727
TI  - New horizons in the treatment of coronary artery thrombosis.
AB  - The application of recombinant DNA methodology to clinical medicine offers the
      clinician a new generation of more potent and specific therapies. Recombinant
      methods offer great promise in the treatment of coronary artery thrombosis. This
      review focuses on the characterization of 1) molecules that activate plasminogen
      locally (in the vicinity of a thrombus) rather than systemically, and 2)
      molecules that offer new approaches to the inhibition of platelet activation and
      thrombin activity. We first describe the methods used to uncover these molecules
      and their characterization at the molecular level. The ways in which this
      knowledge can lead to the development of agents tailored to clinical needs are
      then explored.

PMID- 1994730
TI  - The immunogenetics of hereditary hemochromatosis.
AB  - Hereditary hemochromatosis (HH), an iron overload disease caused by unregulated
      intestinal iron absorption, is a recessive HLA-linked disease. HH is the most
      common inherited metabolic disorder with one of every 400 to 500 individuals
      having both genes and being likely to develop the disease. Thus, although the
      product of the hemochromatosis gene is unknown, its mode of inheritance allows
      HLA-genotyping of the proband and his/her siblings to be highly predictive of the
      genetic propensity to develop the clinical features of HH. In view of the known
      immunoregulatory properties of iron and its binding proteins, it is important to
      determine if the high levels of storage iron in HH influence the
      immunosurveillance network in HH patients and whether that has any clinical
      relevance. We have defined certain alterations of the effector cells of the
      cellular arm of the immune system and have studied a patient with HH who had
      specific immune alterations, including delayed cutaneous-type hypersensitivity
      anergy, and was diagnosed with poorly differentiated adenocarcinoma of the
      stomach four years after his HH diagnosis. Those findings are consistent with the
      interpretation that in certain clinical situations of elevated body iron stores,
      the immunoregulatory balance or environment may be tipped in favor of growth and
      development of cancer cells.

PMID- 1994729
TI  - Comparison of stainable liver iron between symptomatic and asymptomatic
      hemochromatosis homozygotes and their homozygous relatives.
AB  - The authors compared the amount of hepatic parenchymal cell stainable iron in 159
      hemochromatosis homozygotes. They were separated into four groups. Group 1: 59
      symptomatic hemochromatosis probands with hemochromatosis (mean age 49 years) who
      were identified because of symptoms and signs of iron overload. Group 2: 38
      asymptomatic probands with hemochromatosis (mean age 29 years) identified during
      population screening studies or during routine health maintenance evaluation.
      Group 3: 47 homozygous relatives (mean age 43 years) of Group 1 probands. Group
      4: 15 homozygous relatives (mean age 30 years) of Group 2 probands. The
      symptomatic probands (Group 1) were 20 years older and had much more stainable
      hepatic iron (p less than 0.0001) than the asymptomatic probands (Group 2). The
      homozygous relatives (Group 3) of the symptomatic probands also were older and
      had much more stainable hepatic iron than the homozygous relatives (Group 4) of
      asymptomatic probands (p less than 0.0002). The results of this study suggest
      that population screening studies can result in early identification of
      individuals with hemochromatosis before massive hepatic iron overload occurs and
      before symptoms of iron overload develop.

PMID- 1994731
TI  - The immune system in hereditary hemochromatosis: a quantitative and functional
      assessment of the cellular arm.
AB  - The objective of this investigation was to evaluate certain quantitative and
      functional characteristics of the effector cells of the cellular arm of the
      immune system in hereditary hemochromatosis (HH) with respect to treatment
      status. Two observations were consistent with the postulate that the elevated
      levels of storage iron has in vivo immunoregulatory properties: (1) the absolute
      number of CD8-positive T cells were significantly elevated in untreated HH
      patients (n = 7) and reduced in treated patients (n = 7), as compared with
      controls; and (2) the proliferative response of peripheral blood mononuclear
      cells from untreated HH patients to mitogens was suboptimal but the response of
      peripheral blood mononuclear cells (PBM) from treated HH patients was normal.
      Furthermore, immunoglobulin secretion by PBM from treated HH patients as compared
      to controls was altered. Finally, one T effector cell abnormality was unrelated
      to treatment status in that a subset of mature, non-activated T lymphocytes
      aberrantly formed thermostable erythrocyte-rosettes (TE-R), a lymphoid surface
      marker usually expressed on thymocytes or activated T cells. Taken together these
      data define certain immune alterations that are consistent with the
      interpretation that cellular immunity may be influenced by the high level of
      storage iron in HH patients.

PMID- 1994732
TI  - Integrins and cellular adherence molecules in skin.

PMID- 1994733
TI  - Expression of beta 1 integrins in normal human keratinocytes.
AB  - The majority of cell adhesive events to the extracellular matrix are mediated by
      cell surface receptors, beta 1 integrins. Keratinocytes express at least six
      different polypeptides of beta 1 integrin class, namely beta 1, alpha 2, alpha 3,
      alpha 5, and alpha 6 (alpha 6 is mainly associated with beta 4 polypeptide).
      These epithelial cells use alpha 2 beta 1 as a collagen receptor and alpha 3 beta
      1 as a fibronectin receptor, while alpha 6 beta 4 is the major basement membrane
      receptor. Expression of alpha 5 beta 1 complex is low. Processing of beta 1
      integrins is fast in keratinocytes; half-maximal maturation takes only 3 hours.
      In addition to their function in cell-matrix interactions, beta 1 integrins
      (alpha 2 beta 1 and alpha 3 beta 1) have also a role in maintaining keratinocyte
      cell-cell interactions. It is possible that resting basal keratinocytes use beta
      1 integrins as cell-cell adhesion receptors, and during activation, like in wound
      healing, these receptors relocalize to mediate events involving cell-matrix
      interactions.

PMID- 1994734
TI  - The clinical spectrum of thrombocytosis and thrombocythemia.
AB  - Platelet production is the result of a highly ordered maturation of a
      developmental hierarchy of megakaryocytic progenitor cells regulated by a variety
      of cytokines. GM-CSF, II-3 and II-6 have a stimulatory effect and several
      cytokines (TGF-beta, platelet released glycoprotein, platelet factor 4 and
      interferons) have inhibitory effects down regulating platelet production perhaps
      as part of an autocrine control loop. Excess platelet production can be
      clinically characterized as pseudothrombocytosis, thrombocytosis or
      thrombocythemia; the clinical features and criteria for each are defined. The
      term thrombocytosis infers its reactive nature and, in the absence of arterial
      disease or prolonged immobility, it poses little risk regardless of platelet
      numbers. By contrast, in thrombocythemia, whether primary or associated with
      other myeloproliferative lesions, significant thrombohemorrhagic events occur.
      The natural history, rationale, and approach to platelet reduction and control of
      clinical sequela are reviewed. Clinical therapeutic options include a new agent,
      Anagrelide.

PMID- 1994735
TI  - Older Americans present a double challenge: preventing disability and providing
      care.

PMID- 1994736
TI  - Agent Orange: exposure and policy.

PMID- 1994737
TI  - Research on women's health.

PMID- 1994738
TI  - Psychosocial factors in maternal phenylketonuria: prevention of unplanned
      pregnancies.
AB  - BACKGROUND: Women with phenylketonuria (PKU) not treated prior to conception can
      have a pregnancy that results in serious fetal damage. In this report, factors
      associated with preventing unplanned (and hence late treated) pregnancies are
      described. METHODS: Subjects included 60 phenylketonuric women and two comparison
      groups composed of female acquaintances and diabetic women. All were interviewed
      and administered tests of intelligence, general well-being, knowledge, and
      personality. RESULTS: Thirty-five percent of the sexually active women with PKU
      used contraception only sporadically. The variables that best predicted reported
      frequency of birth control use were the extent to which women felt social support
      to use contraception (r = .64) along with positive attitudes about birth control
      (r = .66) and knowledge of family planning (r = .43). For the comparison groups,
      a different pattern of variables predicted contraceptive use, with locus of
      control figuring most prominently for the diabetics (r = .39) and social support
      for birth control being most important for the acquaintances (r = .46).
      CONCLUSIONS: As more girls with PKU enter childbearing ages, there will be an
      increased need for specific programs that address psychosocial factors in
      maternal PKU.

PMID- 1994739
TI  - Predicting onset and chronicity of women's problem drinking: a five-year
      longitudinal analysis.
AB  - BACKGROUND: Longitudinal studies of adult drinking have typically excluded or
      sampled only small numbers of problem drinking women, and have measured a limited
      range of influences on women's drinking behavior. METHODS: To study the
      development of women's problem drinking over time, five-year follow-up interviews
      were conducted with two groups of respondents from a 1981 national survey of
      women's drinking: 143 problem drinkers and 157 nonproblem drinkers. Regression
      analyses examined effects of 1981 predictors on six measures of 1986 problem
      drinking, for problem drinkers and nonproblem drinkers separately. RESULTS: Among
      1981 nonproblem drinkers, predictors of onset of problem drinking indicators by
      1986 included younger age, cohabiting, and lifetime use of drugs other than
      alcohol. The most consistent predictor of persistent (chronic) problem drinking
      was sexual dysfunction; other predictor included being employed part-time or
      never married, and experiencing recent depression. Divorce or separation
      predicted lower levels of subsequent alcohol dependance among problem drinkers.
      CONCLUSIONS: Findings suggest that different personal and social factors predict
      the onset of problem drinking as compared with its continuation, and point to
      nontraditional life-style, sexual dysfunction, and role deprivation as
      potentially important variables.

PMID- 1994740
TI  - Gender differences in cigarette smoking and quitting in a cohort of young adults.
AB  - BACKGROUND: Smoking among young women is associated with a variety of negative
      health outcomes. Gender specific influences on smoking, quitting and attempting
      to quit are hypothesized to occur and may have implications for cessation
      programs. METHODS: Telephone surveys were conducted in a large (n = 6,711) cohort
      of young men and women (average age 19.2 years) which was first established in
      1979 and has been resurveyed several times since then. Questions concerned
      smoking, successful and unsuccessful attempts to quit, withdrawal symptoms during
      quit attempts, and concerns about quitting. RESULTS: More women than men reported
      current smoking (26.5 vs 22.6 percent), but quitting attempts, successful and
      unsuccessful, were equally common. Withdrawal symptoms were reported equally,
      except for wanting to eat more than usual and weight gain, both of which were
      reported more often by women than men. Women smokers reported substantially more
      concern about weight gain if they quit smoking (57.9 vs 26.3 percent expressing
      concern). CONCLUSIONS: Targeted programs are needed to address issues of concern
      to young women smokers, particularly fear of gaining weight.

PMID- 1994741
TI  - Intake of tapwater and total water by pregnant and lactating women.
AB  - BACKGROUND: Despite theoretically higher requirements for water due to
      physiologic demands of pregnancy and lactation, little is known of actual ranges
      of intake in pregnant and lactating women. METHODS: Population-based estimates of
      total water and tapwater intake in women of reproductive age were derived using
      data from the 1977-78 USDA Nationwide Food Consumption Survey. Three-day average
      intakes were calculated for 188 pregnant women, 77 lactating women, and 6,201 non
      pregnant, non-lactating control women. RESULTS: Total water intake (mean +/- SD)
      was 1,940 +/- 686 g/day (median 1,835) for control women, 2,076 +/- 743 g/day
      (median 1,928) for pregnant women and 2,242 +/- 658 g/day (median 2,164) for
      lactating women. Tapwater intake was 1,157 +/- 635 g/day (median 1,065) for
      control women, 1,189 +/- 699 g/day (median 1,063) for pregnant women, and 1,310
      +/- 591 g/day (median 1,330) for lactating women. Total water intake was equal to
      or greater than 3,000 g/day among 7 percent of control women, 11 percent of
      pregnant women, and 13 percent of lactating women. Tapwater intake was equal to
      or greater than 2,000 g/day among 10 percent of control women, 15 percent of
      pregnant women, and 8 percent of lactating women. CONCLUSIONS: These results
      should be useful in estimating amounts of nutrients and toxic substances that
      women of reproductive age obtain through the water supply.

PMID- 1994742
TI  - Regression-adjusted small area estimates of functional dependency in the
      noninstitutionalized American population age 65 and over.
AB  - Health planning efforts for the population age 65 and over have been hampered
      continually by the lack of reliable estimates of the noninstitutionalized long
      term care population. Until recently national estimates were virtually
      nonexistent, and reliable small area estimates remain unavailable. However, with
      the recent publication of several national surveys and the 1990 Census, synthetic
      estimates can be made for states and counties by using multivariate methods to
      model functional dependency at the national level, and then applying the
      predicted probabilities to corresponding state and county data. Using the 1984
      National Health Interview Survey's Supplement on Aging and the 1986 Area Health
      Resources File System, we have produced log-linear regression models that include
      demographic and contextual variables as predictors of functional dependency among
      the noninstitutionalized population age 65 and over. Age, sex, race, and the
      percent of the 65 and over population who reside in poverty were found to be
      significant predictors of functional dependency. Applying these models to 1986
      Medicare Enrollment Statistics, regression-adjusted synthetic estimates of two
      levels of functional dependency were produced for all states and--as examples of
      how the rates can be used to produce additional synthetic estimates--the largest
      county in each state. We also produced point estimates and standard errors for
      the national prevalence of functional dependency among the noninstitutionalized
      population age 65 and over.

PMID- 1994743
TI  - Dioxins and dibenzofurans in adipose tissue of US Vietnam veterans and controls.
AB  - The primary reason for concern about the adverse effects of exposure to Agent
      Orange is attributable to its toxic contaminant, 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD) or dioxin. We studied adipose tissues from 36 Vietnam veterans, a
      similar group of 79 non-Vietnam veterans, and 80 civilians; the tissue specimens
      were selected from the 8,000 archived tissues collected from the non
      institutionalized general population by the US Environmental Protection Agency.
      The geometric mean (+/- standard deviation) dioxin levels in adipose tissue for
      Vietnam veterans, non-Vietnam veterans, and civilian controls were 11.7 (+/-
      1.7), 10.9 (+/- 1.7), and 12.4 (+/- 1.9) parts per trillion on a lipid weight
      basis, respectively. The mean levels for these groups were not significantly
      different from each other with or without adjustment for age of individuals, body
      mass index, and specimen collection year. In addition, none of the surrogate
      measures of Agent Orange exposure such as military branch, service within
      specific geographic region, military occupation, and troop location in relation
      to recorded Agent Orange spray was associated with the dioxin levels in adipose
      tissue of Vietnam veterans. Our results suggest that heavy exposure to Agent
      Orange or dioxin for most US troops was unlikely.

PMID- 1994744
TI  - The UCLA population studies of CORD: X. A cohort study of changes in respiratory
      function associated with chronic exposure to SOx, NOx, and hydrocarbons.
AB  - Two never-smoking cohorts in Southern California, one in Lancaster (N = 2340)
      exposed only to moderate levels of oxidants and the other in Long Beach (N =
      1326) exposed to high levels of SOx, NO2, hydrocarbons and particulates completed
      spirometry and the single-breath nitrogen test five to six years apart. Forty
      seven percent and 45 percent of the participants were retested. Mean results at
      baseline for those tested and not retested were similar. Loss to follow-up was
      primarily due to moving (39 percent and 47 percent). Every difference of
      consequence indicated greater deterioration in lung function in Long Beach. The
      level of significance of the difference was greatest, even in the youngest age
      groups, for delta N2(750-1250), suggesting that the earliest site of impairment
      may occur in the small airways. Greater deterioration in spirometric parameters
      was observed in every age group in Long Beach females above seven years of age at
      baseline and in Long Beach males above 15 years of age, suggesting that chronic
      exposure to the pollutant mix occurring in Long Beach ultimately adversely
      affects the large airways as well as small airways.

PMID- 1994745
TI  - A measles outbreak at a college with a prematriculation immunization requirement.
AB  - BACKGROUND: In early 1988 an outbreak of 84 measles cases occurred at a college
      in Colorado in which over 98 percent of students had documentation of adequate
      measles immunity (physician diagnosed measles, receipt of live measles vaccine on
      or after the first birthday, or serologic evidence of immunity) due to an
      immunization requirement in effect since 1986. METHODS: To examine potential risk
      factors for measles vaccine failure, we conducted a retrospective cohort study
      among students living in campus dormitories using student health service
      vaccination records. RESULTS: Overall, 70 (83 percent) cases had been vaccinated
      at greater than or equal to 12 months of age. Students living in campus
      dormitories were at increased risk for measles compared to students living off
      campus (RR = 3.0, 95% CI = 2.0, 4.7). Students vaccinated at 12-14 months of age
      were at increased risk compared to those vaccinated at greater than or equal to
      15 months (RR = 3.1, 95% CI = 1.7, 5.7). Time since vaccination was not a risk
      factor for vaccine failure. Measles vaccine effectiveness was calculated to be
      94% (95% CI = 86, 98) for vaccination at greater than or equal to 15 months.
      CONCLUSIONS: As in secondary schools, measles outbreaks can occur among highly
      vaccinated college populations. Implementation of recent recommendations to
      require two doses of measles vaccine for college entrants should help reduce
      measles outbreaks in college populations.

PMID- 1994747
TI  - Elevated nicotine levels in cervical lavages from passive smokers.
AB  - One hundred forty-five nonsmokers found to have normal cytologic diagnoses on
      routine Pap smears were interviewed regarding environmental exposure to tobacco
      smoke, and a 3 ml saline lavage of the cervix was collected for measurement of
      cervical nicotine levels by gas chromatography-mass spectroscopy. Nicotine levels
      tended to be highest among women exposed to tobacco smoke in the home,
      intermediate in women exposed only outside the home, and lowest in women
      recalling no exposure (p = 0.001).

PMID- 1994746
TI  - Racial/Ethnic differences in smoking, drinking, and illicit drug use among
      American high school seniors, 1976-89.
AB  - BACKGROUND: This paper reports racial/ethnic differences in the use of licit and
      illicit drugs by high school seniors in the United States. METHODS: The study
      uses questionnaire data from annual, nationally representative surveys of seniors
      from 1976 through 1989. Combined sample sizes were 57,620 for 1976-79; 75,772 for
      1980-84; and 73,527 for 1985-89. RESULTS: Native American had the highest
      prevalence rates for cigarettes, alcohol, and most illicit drugs; White students
      had the next highest rates for most drugs. Asian Americans had the lowest
      prevalence rates, and Black students had levels nearly as low except for
      marijuana. Prevalence rates for the Hispanic groups were mostly in the
      intermediate ranges except for relatively high cocaine use among the males. Trend
      patterns for most forms of drug use were similar across subgroups, although
      cigarette use declined more sharply for Black than White seniors, resulting in
      greater Black-White differences in recent years. CONCLUSIONS: This study, other
      school-based studies, and general population surveys all show relatively low
      levels of drug use by most non-White youth, especially Black Americans and Asian
      Americans. Multivariate analyses indicate that such subgroup differences in high
      school seniors' drug use are not primarily attributable to family composition,
      parents' education, region, or urban-rural distinctions.

PMID- 1994748
TI  - Ascertainment of maternal deaths in New York City.
AB  - Maternal deaths in New York City are defined as deaths from any cause in a woman
      while pregnant or within six months of pregnancy termination. Pilot studies
      seeking to improve maternal death ascertainment found that selected medical
      examiner reports contributed an additional 10.5 percent of the total maternal
      deaths, vital statistics review contributed 6.3 percent, linkage of death tapes
      of women of reproductive age to live birth and fetal death tapes contributed 1.0
      percent. Medical examiner cases should be incorporated into surveillance data for
      accurate ascertainment of pregnancy associated deaths.

PMID- 1994749
TI  - Oral public health programs for the elderly: 1989.
AB  - Forty-eight of the 50 state dental directors, program managers, or state health
      officials were interviewed by telephone about the nature of current oral health
      programs for the elderly and factors that aided or hindered the development of
      such programs. Oral health programs for the elderly were reported in 30 states
      (63 percent of respondents). A majority of respondents indicated that a perceived
      or documented need for oral health programs for the elderly and lobbying by local
      advocacy groups were instrumental in implementing or planning such programs.

PMID- 1994751
TI  - Using a state cancer registry to increase screening behaviors of sisters and
      daughters of breast cancer patients.
AB  - The Pennsylvania Cancer Registry was used to contact breast cancer patients and,
      through them, their adult sisters and daughters. The sisters and daughters were
      counseled concerning their higher than average risks for breast cancer and their
      need for mammography and breast self-examination. Results showed a 9 percent
      increase in mammography and a 10 percent increase in breast self-examination
      rates for the counseled over control group. Costs were $49 per counseled sister
      or daughter indicating a need to increase cost effectiveness before
      implementation is practical.

PMID- 1994750
TI  - Effect of pregnancy during TMI crisis on mothers' mental health and their child's
      development.
AB  - Five years after the Three Mile Island nuclear accident, the mental health of
      women who had been pregnant and living within 10 miles of Three Mile Island at
      the time of the accident was similar to that of women from the same area who
      became pregnant after the accident. Ratings of the development of the two groups
      of children when they were 5 years old were also similar. However, women who were
      pregnant during the crisis and had been "extremely disturbed" about their
      pregnancies rated their children's health as poorer than did the women who were
      pregnant later.

PMID- 1994752
TI  - An eight-year study of oral carcinoma in an elderly black population.

PMID- 1994753
TI  - Birthweight and infant mortality in blacks.

PMID- 1994754
TI  - Cauda equina syndrome after continuous spinal anesthesia.
AB  - Four cases of cauda equina syndrome occurring after continuous spinal anesthesia
      are reported. In all four cases, there was evidence of a focal sensory block and,
      to achieve adequate analgesia, a dose of local anesthetic was given that was
      greater than that usually administered with a single-injection technique. We
      postulate that the combination of maldistribution and a relatively high dose of
      local anesthetic resulted in neurotoxic injury. Suggestions that may reduce the
      potential for neurotoxicity are discussed. Use of a lower concentration and a
      "ceiling" or maximum dose of local anesthetic to establish the block should be
      considered. If maldistribution of local anesthetic is suspected (as indicated by
      a focal sensory block), the use of maneuvers to increase the spread of local
      anesthetic is recommended. If such maneuvers prove unsuccessful, the technique
      should be abandoned.

PMID- 1994755
TI  - Should you cancel the operation when a child has an upper respiratory tract
      infection?
AB  - Cancelling an operation when a child has an upper respiratory tract infection
      (URI) is not always feasible or practical. Yet we know very little about the
      additional risk posed by a URI occurring in a child undergoing anesthesia and
      surgery. Using a large prospectively collected pediatric anesthesia database, we
      studied 1283 children with a preoperative URI and 20,876 children without a URI.
      We found that children with a URI were two to seven times more likely to
      experience respiratory-related adverse events during the intraoperative, recovery
      room, and postoperative phases of their operative experience. Although these
      children also experienced significant disruptions in temperature regulation, they
      were not at risk for any other deleterious events. The elevation in risk after
      URI as compared with children without a URI was not explained by differences in
      age, physical status scores, surgical site, and emergency or elective status.
      However, if a child had a URI and had endotracheal anesthesia, the risk of a
      respiratory complication increased 11-fold (95% confidence intervals 6.8, 18.1).
      We conclude that the administration of general anesthesia to children with a URI
      is not benign and that these children require more observation/management in all
      perioperative phases of their surgical procedure.

PMID- 1994756
TI  - Influence of desflurane on regional distribution of coronary blood flow in a
      chronically instrumented canine model of multivessel coronary artery obstruction.
AB  - The influence of desflurane on myocardial perfusion measured by a microsphere
      technique during a total occlusion of the left anterior descending coronary
      artery and concomitant moderate or severe stenosis of the left circumflex
      coronary artery was evaluated in chronically instrumented dogs. Hemodynamics,
      regional contractile function, and myocardial blood flow were measured during the
      conscious state and after anesthesia with desflurane (8.2%-9.2% and 12.5%-12.7%)
      with and without control of arterial pressure. Total left anterior descending
      occlusion produced in combination with a left circumflex coronary artery stenosis
      significantly (P less than 0.05) increased heart rate and left ventricular end
      diastolic pressure in the absence of desflurane anesthesia. Desflurane,
      administered only in the presence of left anterior descending occlusion and left
      circumflex stenosis, significantly (P less than 0.05) decreased mean arterial
      pressure, left ventricular systolic pressure, and left ventricular positive
      dP/dt50 without change in heart rate. Blood flow to the subendocardium of normal
      myocardium was reduced during the high concentration of desflurane (P less than
      0.05), but perfusion of the subepicardium and midmyocardium was maintained at
      conscious levels. When the left circumflex stenosis was of moderate severity,
      only blood flow to the subendocardium distal to the stenosis was reduced by
      desflurane (P less than 0.05). In the presence of a severe stenosis, perfusion
      was decreased in the subepicardium, midmyocardium, and subendocardium of the
      stenotic zone (P less than 0.05). During the reduction in arterial pressure
      produced by desflurane, collateral blood flow in the left anterior descending
      region was reduced in dogs with either a moderate or severe left circumflex
      stenosis (P less than 0.05). When arterial pressure and heart rate conditions
      observed in the postocclusion conscious state were restored during the high
      concentration of desflurane, myocardial blood flow in all regions returned to
      those levels present in the conscious state (P less than 0.05). Ratios of flow
      between occluded and normal zones were decreased when hypotension produced by
      desflurane was uncontrolled, but when arterial pressure and heart rate were
      adjusted to conscious postocclusion levels using partial thoracic aorta occlusion
      and atrial pacing, the ratio remained at conscious control levels regardless of
      the degree of left circumflex stenosis severity (P less than 0.05). Results of
      this investigation indicate that desflurane does not redistribute blood flow away
      from collateral-dependent myocardium to other regions via a "coronary steal"
      mechanism in a chronically instrumented canine model of multivessel coronary
      artery disease.

PMID- 1994758
TI  - Patient-controlled sedation during epidural anesthesia.
AB  - The purpose of this study was to evaluate the feasibility and advantages or
      disadvantages, if any, of patient-controlled sedation compared with sedation
      administered by the anesthesiologist during surgical epidural anesthesia. Forty
      patients were divided at random into two groups with 20 patients in each group.
      Patients in group 1 received 0.5-1.0 mg intravenous midazolam and 25-50
      micrograms intravenous fentanyl in increments administered by the
      anesthesiologist to achieve intraoperative sedation; patients in group 2 self
      administered a mixture of midazolam (0.5 mg) and fentanyl (25 micrograms) in
      increments using an Abbott Lifecare PCA infuser to achieve sedation. Demographics
      of the patients, the types of surgery performed, doses of midazolam and fentanyl
      administered in a given period of time, and the level of sedation maintained
      during epidural anesthesia and surgery were similar in both groups. Patients in
      the self-administered group, however, rated their level of comfort during
      anesthesia and surgery higher than did those in the anesthesiologist-controlled
      sedation group. This could have been due to a positive psychological effect
      produced by allowing patient to feel that they have some control over their
      situation. The findings of this study indicate that patient-controlled sedation
      using a combination of midazolam and fentanyl is a safe and effective technique
      that provides intraoperative sedation ranked better by patients than that
      provided by anesthesiologists using the same drugs. More studies are, however,
      needed to determine the best choice of drug(s), the doses, the lock-out
      intervals, and the possible use of continuous infusion with patient-controlled
      sedation.

PMID- 1994757
TI  - Continuous postoperative regional analgesia by nerve sheath block for amputation
      surgery--a pilot study.
AB  - A pilot study of continuous postoperative regional analgesia by nerve sheath
      block for lower limb amputation is presented. At the time of exposure of sciatic
      or posterior tibial nerve trunks during above- or below-knee amputations in 11
      patients with ASA physical status III or IV, a catheter was introduced directly
      into the transected nerve sheath for continuous infusion of 0.25% bupivacaine at
      a rate of 10 mL/h for 72 h. Effective amputation stump analgesia was obtained,
      significantly reducing the need for on-demand narcotic analgesics during this
      time to a mean dose equivalent of 1.4 mg of morphine compared with a
      retrospective control group who received the equivalent of a mean dose of 18.4 mg
      of morphine (P less than 0.0001). No complications related to the technique were
      observed. A follow-up of the group receiving continuous postoperative regional
      analgesia for up to 12 mo showed a total absence of phantom pain despite the
      presence of preoperative limb pain.

PMID- 1994759
TI  - Role of experience in the response to simulated critical incidents.
AB  - Eight experienced anesthesiologists (faculty or private practitioners) were
      presented with the same simulated critical incidents that had previously been
      presented to 19 anesthesia trainees. The detection and correction times for these
      incidents were measured, as was compliance with Advanced Cardiac Life Support
      (ACLS) guidelines during cardiac arrest, and the occurrence of unplanned
      incidents. Experienced personnel tended to react more rapidly than did trainees,
      but differences between second-year anesthesia residents (CA2) and experienced
      anesthesiologists were not statistically significant. There was a high
      variability in performance between incidents and within each group. Unplanned
      errors and management flaws still occurred with experience subjects. The response
      to incidents during anesthesia is a complex process that involves multiple levels
      of cognitive activity and is vulnerable to error regardless of experience. Most
      trainees seemed to acquire adequate response routines by the end of the CA2 year.
      Formal reasoning appeared to play a minor role in responding to intraoperative
      events, but the exact nature of the anesthesiologist's cognition remains to be
      thoroughly investigated.

PMID- 1994760
TI  - Comparison of kinetics of sevoflurane and isoflurane in humans.
AB  - The low solubility of sevoflurane in blood suggests that this agent should enter
      and leave the body more rapidly than isoflurane. However, the closeness of
      sevoflurane and isoflurane tissue/blood partition coefficients suggests that the
      rates of equilibration with and elimination from tissues should be similar. We
      tested both predictions, comparing sevoflurane with isoflurane and nitrous oxide
      in seven volunteers. We measured the rate at which the alveolar (end-tidal) (FA)
      concentration of nitrous oxide increased toward an inspired (FI) concentration of
      65%-70%, then measured the concurrent rise in FA and mixed expired concentrations
      (FM) of sevoflurane and isoflurane at respective FI values of 1.0% sevoflurane
      and 0.6% isoflurane for 30 min. Minute ventilation (VE) was measured concurrently
      with the measurements of anesthetic concentrations. For the potent agents, we
      also measured VE, FA, and FM for 6-7 days of elimination. FA/FI values at 30 min
      of administration were as follows: nitrous oxide, 0.986 +/- 0.003 (mean +/- SD);
      sevoflurane, 0.850 +/- 0.018; and isoflurane, 0.733 +/- 0.027. FA/FA0 (FA0 = the
      last FA during administration) values after 5 min of elimination were as follows:
      sevoflurane, 0.157 +/- 0.020; isoflurane, 0.223 +/- 0.024. Recovery (volume of
      anesthetic recovered during elimination/volume taken up) of sevoflurane (101% +/-
      7%) equaled recovery of isoflurane (101% +/- 6%). Time constants for a five
      compartment mammillary model for sevoflurane were smaller than those for
      isoflurane for the lungs but were not different from isoflurane for the other
      compartments.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1994761
TI  - Low-dose clonidine enhances pregnancy-induced analgesia to visceral but not
      somatic stimuli in rats.
AB  - This is one of a series of experiments designed to examine the possible
      pharmacologic basis for analgesia normally associated with pregnancy. The
      antinociceptive effects of low-dose (0.1 mg/kg) subcutaneous clonidine on
      analgesia associated with pregnancy were evaluated in rats. Colorectal distention
      thresholds and tail-flick latencies were determined in timed pregnant rats (n =
      27) before mating, on days 7 and 21 of gestation, and on postpartum day 7.
      Immediately after baseline testing on each of those days, animals received 0.1
      mg/kg clonidine subcutaneously and were retested 30 min later. On day 21 of
      gestation, 20 micrograms/kg naloxone (n = 9) and 0.2 mg/kg yohimbine (n = 5) were
      intravenously administered after clonidine testing, and animals were retested 15
      min later. In the absence of clonidine, pregnant animals demonstrated a
      statistically significant increase in their tolerance of colorectal distention
      pressures and longer latencies to tail-flick withdrawal on day 21 of gestation.
      Clonidine produced a further significant increase in distention thresholds on day
      21 of gestation but did not change these thresholds on any other day, nor did it
      change tail-flick latencies. Naloxone and yohimbine reversed the effect of
      clonidine on the distention thresholds on day 21. Systemic clonidine, at a dose
      lower than that required to produce antinociception in nonpregnant rats, enhanced
      pregnancy-induced analgesia to visceral stimulation late in pregnancy, an effect
      that was reversed by naloxone and yohimbine. These results suggest a synergistic
      antinociceptive effect of clonidine due to an interaction with an endogenous
      opiate system that is only activated late in pregnancy.

PMID- 1994762
TI  - Low-dose bupivacaine does not improve postoperative epidural fentanyl analgesia
      in orthopedic patients.
AB  - Epidural infusions of 10 micrograms/mL fentanyl combined with low-dose
      bupivacaine (0.1%) were compared with epidural infusions of fentanyl alone for
      postoperative analgesia after total knee joint replacement. There were no
      detectable differences between the two groups in analgesia (visual analogue scale
      ranging between 15 and 40 mm), infusion rates (which averaged 7-9 mL/h), or serum
      fentanyl levels (which reached 1-2 ng/mL). The incidence of side effects,
      including nausea, vomiting, and pruritus, was also similar. Of the patients
      receiving fentanyl and low-dose bupivacaine, one developed a transient unilateral
      motor and sensory loss, and one developed significant hypotension and respiratory
      depression. The addition of low-dose bupivacaine does not improve epidural
      fentanyl infusion analgesia after knee surgery and may increase morbidity.

PMID- 1994763
TI  - Long-latency auditory evoked potentials during general anesthesia: N1 and P3
      components.
AB  - The N1 and P3 auditory evoked potentials were recorded to evaluate their
      usefulness as measures of the level of consciousness in 14 ASA physical status I
      and II patients undergoing elective surgery. The anesthetic agents were
      thiopental, fentanyl, and isoflurane with or without nitrous oxide. Recordings
      were carried out before induction (preinduction) and during induction, surgical
      anesthesia, emergence, and recovery from anesthesia. The auditory response was
      evoked by 700-Hz tones that occurred occasionally and unpredictably in a train of
      500-Hz tones delivered at 40 per second. The patients were asked to press a
      button whenever they detected a 700-Hz tone. Studies with normal subjects have
      repeatedly shown that detected tones (HITS) evoke N1 and P3 waves, whereas
      undetected tones (MISSES) evoke no recognizable waves. The responses evoked by
      HITS were compared with those evoked by MISSES. The amplitudes of N1 and P3 were
      significantly different from zero for HITS before induction and during induction
      and recovery but not during emergence. The amplitudes of N1 and P3 were not
      different from zero for MISSES during induction, surgery, and emergence. During
      recovery, the N1 and P3 for MISSES were small and the P3 for HITS was
      significantly larger than for MISSES. The results indicate that except during
      emergence, HITS were associated with clear N1 and P3 waves, whereas MISSES were
      not. The lack of either N1 or P3 for HITS during emergence perhaps occurred
      because the patients, although responsive, were not yet fully conscious. The N1
      and P3 components of the auditory evoked potential may provide specific
      indicators for consciousness.

PMID- 1994764
TI  - Vagal involvement in the action of exogenous adenosine triphosphate on reflex
      renal sympathetic nerve activity.
AB  - The reason why adenine compounds when used as hypotensive agents are devoid of
      significant reflex sympathetic activity, such as rebound hypertension and
      tachycardia, is not clearly understood. This study, performed on alpha-chloralose
      anesthetized dogs, examined, first, the effects of adenosine triphosphate (ATP)
      and adenosine as compared with those of sodium nitroprusside on efferent renal
      sympathetic nerve activity (RSNA), as an indicator of general reflex sympathetic
      activity, and second, whether vagal involvement could be demonstrated in the
      action of ATP and adenosine on RSNA. Renal sympathetic nerve activity increased
      progressively with increasing doses of sodium nitroprusside (5, 10, and 20
      micrograms/kg) and adenosine (0.5, 2.0, and 4.0 mg/kg), whereas ATP suppressed
      RSNA at 2.0 and 4.0 mg/kg. High doses of ATP and adenosine (4.0 mg/kg) were
      injected into intact (n = 7) and vagotomized dogs (n = 7). Both ATP and adenosine
      induced rapid onset of hypotension without rebound hypertension and tachycardia.
      After vagotomy, the attenuation of RSNA by ATP was completely abolished and
      rebound hypertension and tachycardia were observed. Vagotomy did not alter the
      effect of adenosine on RSNA. It is concluded that ATP-induced hypotension is
      associated with attenuation of sympathetic efferent nerve activity mediated
      through vagal afferent pathways. Vagal afferent impulses are thought to be one of
      the mechanisms that inhibit reflex sympathetic activities, such as rebound
      hypertension after ATP-induced hypotension. The mechanisms by which adenosine
      inhibits reflex sympathetic activity are not, however, secondary to vagal
      afferent involvement and must be multifactorial.

PMID- 1994765
TI  - Effect of ranitidine on bupivacaine disposition.
AB  - This study was undertaken to determine the effect, if any, of ranitidine on
      bupivacaine disposition in 28 women undergoing cesarean section. Before epidural
      anesthesia, ranitidine (50 mg IM) or sodium citrate (30 mL orally) was
      administered to groups of 14 parturients each. Ranitidine was administered 2 h
      before epidural anesthesia and sodium citrate was administered 10 min before the
      epidural. Maternal plasma samples were collected after epidural anesthesia with
      bupivacaine. A total of 15 maternal plasma samples were taken from the time of
      administration of epidural anesthesia up to 180 min. Postpartum plasma and urine
      samples were also collected from both mothers and neonates. Plasma samples were
      collected up to 48 h postpartum at intervals of 12, 24, and 48 h. Urine samples
      were collected at six 6-h intervals up to 36 h postpartum. A two-way analysis of
      variance with repeated measures demonstrated that there was no significant
      difference in bupivacaine levels between the maternal plasma curves of the
      ranitidine and the control groups. At the time of delivery, plasma levels of
      bupivacaine and its N-dealkylated metabolite PPX (2,6-pipecolylxylidine) were no
      different in the mothers or neonates of either group. There was no significant
      difference in plasma protein binding of bupivacaine in the presence of
      ranitidine. The excretion rates of bupivacaine and PPX were not measurably
      influenced by ranitidine. The amount of bupivacaine excreted, the amount of
      metabolite excreted, and the percentage of drug excreted as metabolite in
      maternal urine were not significantly different. These data indicate that there
      is no measurable effect of ranitidine on the disposition of bupivacaine in
      parturients.

PMID- 1994766
TI  - Effect of fentanyl and nitrous oxide on the desflurane anesthetic requirement.
AB  - The minimum alveolar anesthetic concentration (MAC) of desflurane (I-653) was
      determined when administered with 60% nitrous oxide (N2O) in oxygen after a
      standardized induction sequence consisting of 0, 3, 6, or 9 micrograms/kg
      intravenous (IV) fentanyl followed by 3-6 mg/kg IV thiopental and 1.5 mg/kg IV
      succinylcholine. For comparison, we also determined the isoflurane MAC with 60%
      N2O in oxygen after an induction dose of 3 micrograms/kg IV fentanyl and similar
      doses of thiopental and succinylcholine. All patients were undergoing elective
      surgical procedures. The minimum alveolar anesthetic concentration in patients
      given isoflurane and 60% N2O with 3 micrograms/kg fentanyl was 0.4%,
      approximately 20% below previously reported MAC values for isoflurane with 60%
      N2O alone. The minimum alveolar anesthetic concentration of desflurane with 60%
      N2O plus 0, 3, 6, and 9 micrograms/kg IV fentanyl was 3.7%, 3.0%, 1.2%, and 0.1%,
      respectively. Thus, the MAC-lowering effect of 3 micrograms/kg IV fentanyl
      appears to be similar with both isoflurane and desflurane. Fentanyl, 3-9
      micrograms/kg IV, produces dose-dependent decreases in the MAC of desflurane.

PMID- 1994767
TI  - Gardner Quincy Colton: pioneer of nitrous oxide anesthesia.

PMID- 1994768
TI  - Blind nasal intubation with audio-capnometry.

PMID- 1994769
TI  - Onset of amputation stump pain associated with epidural anesthesia.

PMID- 1994771
TI  - Are breech deliveries an indication for lumbar epidural analgesia?

PMID- 1994770
TI  - Speedballs: a new cause of intraoperative tachycardia and hypertension.

PMID- 1994772
TI  - Nightmares and recovery from anesthesia.

PMID- 1994774
TI  - A "loading port" for syringe infusion pumps.

PMID- 1994773
TI  - The importance of documenting complete sympathetic blockade.

PMID- 1994775
TI  - A history of nurse anesthesia?

PMID- 1994776
TI  - Intraspinal opiates in patients receiving podophyllum.

PMID- 1994777
TI  - Oral pulse oximetry in small children.

PMID- 1994778
TI  - Why 70 watts to evaluate metal tapes for CO2 laser surgery?

PMID- 1994779
TI  - Systemic droperidol and epidural morphine in the management of postoperative
      pain.

PMID- 1994780
TI  - Standardization of allergenic extracts.

PMID- 1994781
TI  - Respiratory failure in a seven-month-old baby: an unusual presentation of severe
      immunologic disease.

PMID- 1994782
TI  - The 1990 Bela Schick memorial lecture: teaching the elephant to dance.

PMID- 1994783
TI  - Anaphylaxis to annatto dye: a case report.
AB  - Annatto dye is an orange-yellow food coloring extracted from the seeds of the
      tree Bixa orellana. It is commonly used in cheeses, snack foods, beverages, and
      cereals. Previously reported adverse reactions associated with annatto dye have
      included urticaria and angioedema. We present a patient who developed urticaria,
      angioedema, and severe hypotension within 20 minutes following ingestion of milk
      and Fiber One cereal, which contained annatto dye. Subsequent skin tests to milk,
      wheat, and corn were negative. The patient had a strong positive skin test to
      annatto dye, while controls had no response. The nondialyzable fraction of
      annatto dye on SDS-PAGE demonstrated two protein staining bands in the range of
      50 kD. Immunoblotting demonstrated patient IgE-specific for one of these bands,
      while controls showed no binding. Annatto dye may contain contaminating or
      residual seed proteins to which our patient developed IgE hypersensitivity.
      Annatto dye is a potential rare cause of anaphylaxis.

PMID- 1994784
TI  - Emerging techniques in the diagnosis of sinusitis.
AB  - In recent years, the high prevalence of chronic sinusitis has been noted in
      isolation and in association with bronchial asthma, aspirin sensitivity, and
      perennial rhinitis. Many sinus-associated symptoms arise from nasal rather than
      sinus pathology; thus, it is important to detect the presence, extent, and nature
      of any disease within the sinus cavities. Conventional plain radiographs have
      limited sensitivity and have been supplanted by more widespread use of
      computerized tomography. The role of other modalities such as ultrasound and
      magnetic resonance imaging has not yet been completely determined. Other tests
      such as cytology and endoscopy can detect the presence of infection without the
      need for invasive antral puncture. Practitioners should consider the impact of a
      negative imaging test on their therapeutic plan and order tests on that basis.

PMID- 1994785
TI  - Relationships between skin prick test, radioallergosorbent test, and
      chemiluminescent assays in allergic children.
AB  - The results of skin prick tests (SPT), radioallergosorbent tests (RAST), and
      multiple chemiluminescent tests (DHS-CLA) to grass mix, parietaria, D. farinae,
      and D. pteronyssinus were evaluated in 43 allergic children. All CLA tests had
      valid positive and negative control threads. Chemiluminescent assays class 4
      matched with RAST class 3 and/or 4 and CLA class 3 with RAST class 2. The D.
      farinae, D. pteronyssinus, and grass results obtained with CLA, RAST, and SPT
      were investigated by principal components analysis that showed a good association
      between different methods of measuring allergenicity. The results of the present
      study confirm that DHS-CLA is an effective "in vitro" method for the detection of
      IgE-allergen specific antibody.

PMID- 1994786
TI  - Clustering of fungal allergen-specific IgE antibody responses in allergic
      subjects.
AB  - Statistical analysis of specific IgE immune responses to a panel of nine
      allergens from 2,094 patients demonstrated significant clustering between
      Aspergillus fumigatus, Alternaria alternata, and Cladosporium herbarum, not
      explained by crossreactive elements. This may represent a linked, high responder
      status to these fungal antigens in the allergic population.

PMID- 1994788
TI  - Hypersensitivity reaction to jicama (Pachyrhizus, yam bean).

PMID- 1994787
TI  - A pilot study of pemirolast in patients with seasonal allergic rhinitis.
AB  - Pemirolast is a potent, long-acting, orally effective antiallergic agent
      evaluated for clinical activity in prevention of symptoms of seasonal allergic
      rhinitis. It was evaluated in a randomized, double-blind, placebo-controlled
      parallel group in season trials to test its safety, tolerance, and prophylactic
      activity. Thirty-one patients with a history of fall seasonal allergic rhinitis
      were treated for 6 weeks with pemirolast, 50 mg bid, or placebo beginning
      approximately 2 weeks before the onset of the ragweed season in Atlanta. Daily
      evaluation of symptom scores disclosed statistically significantly less sneezing,
      rhinorrhea, and stuffy nose during treatment with pemirolast. There was, however,
      no difference for other evaluated symptoms or for the use of rescue medicines.
      There were no side effects during this short study. This preliminary study
      indicates that pemirolast may warrant further evaluation for the treatment of
      allergic rhinitis.

PMID- 1994789
TI  - Intestinal permeability in patients with chronic urticaria-angioedema with and
      without arthralgia.
AB  - We evaluated the clinical response to oligoallergenic dietary treatment and the
      intestinal absorption of a protein antigen, cow milk beta-lactoglobulin (BLG) in
      24 patients with chronic urticaria/angioedema syndrome 13 of whom also suffered
      from joint symptoms. Sixteen patients (77% of those with arthralgia) responded to
      diet (RD) with marked reduction of symptoms; the others did not respond (NR). Ten
      (all but one RD with arthralgia) had increased permeability to BLG after oral
      administration of cow milk. Four with high titers of IgG to BLG showed the
      highest absorption of BLG and the groups with arthralgia showed higher BLG levels
      than those without arthralgia. In all cases, specific IgE to cow milk was absent.
      These data suggest that the symptoms of a subgroup of patients with chronic
      urticaria, and especially patients with joint complaints that subside with diet,
      are related to excess intestinal permeability. The measurement of gut
      permeability to food proteins may be useful to define those who may benefit from
      dietary restriction.

PMID- 1994790
TI  - History of merger discussions.

PMID- 1994791
TI  - Pneumothorax in AIDS.
AB  - OBJECTIVE: To determine risk factors for the development of pneumothorax in
      patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: Prospective
      cohort study. SETTING: Tertiary care center. PATIENTS: Of 1030 patients with AIDS
      who were followed at Memorial Sloan-Kettering Cancer Center between 1 January
      1980 and 30 September 1989, 20 (2%) developed pneumothorax that was unrelated to
      trauma or a pulmonary procedure. RESULTS: Of 20 patients with AIDS who presented
      with pneumothorax, 19 had compelling evidence of concurrent Pneumocystis carinii
      pneumonia. Using bivariate analysis, patients receiving aerosol pentamidine
      prophylaxis (relative risk, 17.6) and those with a history of P. carinii
      pneumonia (relative risk, 14.5) were more likely to develop pneumothorax. By
      Mantel-Haenszel stratified analysis, aerosol pentamidine use was a statistically
      significant risk factor independent of a history of P. carinii pneumonia. The
      pneumothorax-related mortality rate was 10% and there was considerable morbidity.
      CONCLUSIONS: Patients with AIDS at the highest risk for developing pneumothorax
      are those with a history of P. carinii pneumonia who are receiving aerosol
      pentamidine prophylaxis but who nevertheless develop P. carinii pneumonia. The
      benefits of aerosol pentamidine prophylaxis in these patients far outweigh this
      risk. Pneumocystis carinii pneumonia should be considered as the most likely
      diagnosis in any patient with AIDS who develops a pneumothorax.

PMID- 1994793
TI  - Increased plasma endothelin-1 in pulmonary hypertension: marker or mediator of
      disease?
AB  - OBJECTIVE: To explore the role of endothelin-1, a potent endothelial-derived
      vasoconstrictor peptide, in pulmonary hypertension, by measuring its
      concentration in arterial and venous plasma. DESIGN: A survey, case series study.
      SETTING: University-affiliated hospitals and outpatient clinics. PATIENTS: Twenty
      seven patients with pulmonary hypertension: 7 with primary, and 20 with secondary
      pulmonary hypertension of various causes. The control groups (n = 16) comprised 8
      healthy volunteers and 8 patients with coronary artery disease but without
      evidence of pulmonary hypertension. MEASUREMENTS AND MAIN RESULTS: Pulmonary
      artery pressure was markedly increased (94/43 +/- 23/13 mm Hg) in the patients
      with pulmonary hypertension. Venous plasma immunoreactive endothelin-1, measured
      by a specific radioimmunoassay, was significantly higher in patients with
      pulmonary hypertension (3.5 +/- 2.5 pg/mL, P less than 0.001) than in normal
      subjects (1.45 +/- 0.45 pg/mL), or patients with coronary disease (0.75 +/- 0.64
      pg/mL). The arterial-to-venous ratio of immunoreactive endothelin-1 was
      significantly greater than unity in primary pulmonary hypertension (2.21 +/-
      0.72, P = 0.01), whereas the patients with secondary pulmonary hypertension had a
      mean ratio not different from 1 (0.97 +/- 0.42). In contrast, the mean arterial
      to-venous ratios were significantly less than unity in both control groups (0.59
      +/- 0.35, and 0.54 +/- 0.64; P less than 0.02, for normal subjects and coronary
      disease patients, respectively), indicating a possible clearance of endothelin-1
      across the healthy lung. CONCLUSIONS: Patient with pulmonary hypertension have
      substantial alterations in plasma immunoreactive endothelin-1, which may reflect
      changes in net release or clearance of endothelin-1 by the lung. In patients with
      primary pulmonary hypertension, the high levels in arterial compared with venous
      plasma suggest pulmonary production of endothelin-1, which may contribute to
      elevated pulmonary vascular resistance.

PMID- 1994792
TI  - Narrow QRS ventricular tachycardia.
AB  - OBJECTIVE: To determine the frequency and clinical characteristics of narrow QRS
      ventricular tachycardia (QRS duration less than or equal to 0.11 seconds).
      DESIGN: Consecutive survey of patients with ventricular tachycardia. SETTING:
      Tertiary, referral-based arrhythmia service at a university medical center.
      PATIENTS: Sequential sample of patients with inducible ventricular tachycardia
      who had a 12-lead electrocardiogram of the tachycardia available for review.
      MEASUREMENTS AND MAIN RESULTS: Of 106 patients with ventricular tachycardia, 5
      (4.7%; 95% CI, 2.1% to 10.6%) had ventricular tachycardia with a QRS duration
      less than or equal to 0.11 seconds. Three of the five patients were previously
      incorrectly diagnosed as having supraventricular tachycardia. All five patients
      had at least two electrocardiographic findings other than QRS duration to suggest
      ventricular tachycardia. CONCLUSIONS: Narrow QRS ventricular tachycardia should
      be considered in the differential diagnosis of narrow QRS tachycardias.
      Electrocardiographic findings other than QRS duration are usually present to
      suggest the diagnosis.

PMID- 1994794
TI  - Immunogenicity of an inactivated hepatitis A vaccine.

PMID- 1994795
TI  - Lyme disease: recommendations for diagnosis and treatment.
AB  - The incidence and the endemic range of Lyme disease in the United States have
      increased steadily since the disease was originally recognized in Lyme,
      Connecticut, in 1975. Because of the varied clinical manifestations of this
      illness and the use of unstandardized serologic testing methods, diagnosis is
      often uncertain and treatment outcomes are often difficult to evaluate. The
      antibiotic regimens that are commonly used in clinical practice have changed
      rapidly. They show much regional variation with little critical comparison of
      treatment results. The clinical diagnosis and the literature on the treatment of
      the various stages of Lyme disease are reviewed. The reported data are
      supplemented with recommendations based on 15 years of clinical experience with
      this illness.

PMID- 1994796
TI  - Teaching medicine as a human experience: a patient-doctor relationship course for
      faculty and first-year medical students.
AB  - We developed a required, longitudinal course for first-year medical students that
      addressed the patient-doctor relationship. Our course linked understanding
      patients' experiences and perspectives on illness with listening to, talking
      with, and establishing a rapport with patients while obtaining their medical
      histories. Learning was enhanced by use of an interdisciplinary faculty and by
      small-group continuity and faculty mentoring. Our curriculum adapted problem
      based, self-directed educational methods to convey medical humanism. We focused
      on bedside interviewing as the means for exploring patients' social, emotional,
      and ethical concerns.

PMID- 1994797
TI  - Diagnosis of Lyme disease based on dermatologic manifestations.
AB  - Lyme disease, or Lyme borreliosis, is an infection caused by the spirochete
      Borrelia burgdorferi, which is most commonly transmitted to humans by a tick
      bite. Characterized by early and late phases, Lyme disease is a multisystem
      illness involving the skin, heart, joints, and nervous system. Diagnosis is based
      predominantly on clinical manifestations, the most specific being dermatologic.
      Thus, recognizing the dermatologic manifestations of Lyme disease is important
      for diagnosis and institution of appropriate, effective therapy. Approximately
      75% of patients with Lyme disease present with the pathognomonic skin lesion
      erythema migrans, an expanding erythematous lesion. During early infection,
      secondary erythema migrans lesions or Borrelia lymphocytoma may occur. Borrelia
      lymphocytoma commonly presents as an erythematous nodule on the ear lobe or
      nipple. During late infection, acrodermatitis chronica atrophicans, an
      erythematous, atrophic plaque unique to Lyme disease may appear; it has been
      described in about 10% of patients with Lyme disease in Europe. Fibrotic nodules
      associated with acrodermatitis chronica atrophicans as well as other sclerotic
      and atrophic lesions, such as morphea, lichen sclerosus et atrophicus,
      anetoderma, and atrophoderma of Pasini and Pierini, have been seen late in the
      course of Lyme disease. In a few cases, other sclerodermatous lesions, such as
      eosinophilic fasciitis and progressive facial hemiatrophy, have been linked to B.
      burgdorferi infection. We review the cutaneous lesions associated with Lyme
      disease.

PMID- 1994798
TI  - Adenosine or verapamil for the acute treatment of supraventricular tachycardia?

PMID- 1994799
TI  - Confidence intervals assess both clinical significance and statistical
      significance.

PMID- 1994800
TI  - The state of internal medicine.

PMID- 1994801
TI  - 1,25(OH)2 vitamin D for osteoporosis.

PMID- 1994802
TI  - Castleman disease-POEMS syndrome overlap.

PMID- 1994803
TI  - Thrombolytic therapy.

PMID- 1994804
TI  - "Seronegative" syphilis in AIDS.

PMID- 1994805
TI  - Accuracy of pelvic examination.

PMID- 1994806
TI  - The iliac crest region: donor site for vascularized bone periosteal and soft
      tissue flaps.
AB  - A review is presented of the classic vascularized iliac crest transfer and to
      show useful variations on this technique. A technical variation to reconstruct
      mandibular defects, the semisegmented iliac crest graft, is described. Another
      variation, the half iliac crest graft, is presented for use in the
      neovascularization of avascular necrosis of the femoral head. When such a flap is
      raised with a large periosteal flap and overlying muscle or skin, or both, as a
      composite flap, a primary osteoperiosteal tube can be created to reconstruct
      segmental defects in long bones. This primary osteoperiosteal tube is secondarily
      transformed into a completely osseous tube.

PMID- 1994807
TI  - Various techniques of secondary nose correction in unilateral cleft-lip
      procedure.
AB  - Several technical details of secondary nose correction in unilateral cleft lip
      procedure are presented. A new technique of total removal of distorted septal
      cartilage is described, correcting it under full vision and replanting it
      afterwards into the nose, thus clearing both airways and reshaping the nose
      profile at the same time. Also different cartilage-mucosal flaps are described as
      a way to create symmetry in the nasal tip region and both ala nasi.

PMID- 1994808
TI  - Plastic surgery in Germany.

PMID- 1994809
TI  - Plastic surgery on identical twins.
AB  - Four pairs of identical female twins have undergone a variety of plastic surgery
      procedures, including rhinoplasties, rhytidectomies, augmentation mammaplasties,
      and trochanteric liposuction. Performing plastic surgery on identical twins
      implies special considerations: the extent of preoperative phenotypic identity,
      the behavior of each twin (dominant or recessive), the twins' personal
      interdependence and individual expectations, the operative strategy (simultaneous
      versus sequential operations), the eventual complications, and the extent to
      which the operative results and postoperative appearance are identical. In
      general, counseling, operative technique, and responsibility for producing good
      results place greater demands on surgeons when performing plastic surgery on
      identical twins than on singletons. Still, the results have been gratifying.

PMID- 1994810
TI  - German pioneers and teachers of plastic and reconstructive surgery: a selection.

PMID- 1994811
TI  - The proximally pedicled arteria radialis forearm flap in the treatment of soft
      tissue defects of the dorsal elbow.
AB  - Soft tissue defects of the dorsal side of the elbow require a stable soft tissue
      reconstruction. Therefore, for the treatment of limited, uninfected defects,
      local or distant skin flaps should be used. For large and infected defects, the
      use of the proximally pedicled arteria radialis forearm flap is indicated. We
      used the flap in 14 patients as an alternative to conventional methods. This
      neurovascular, septocutaneous flap proved safe and versatile, guaranteeing stable
      soft tissue reconstruction of the dorsal aspect of the elbow. The flap has an
      orthograde flow and is nourished by the radial artery. With its long,
      neurovascular pedicle, it can be transposed in a proximal ulnar or radial
      direction. Four years after operation, all elbow joints showed a complete range
      of motion. No further soft tissue instabilities were seen.

PMID- 1994812
TI  - Asymmetrical cranio-orbital facial stenosis.
AB  - Cranio-orbital facial scoliosis is the result of unilateral premature stenosis of
      the craniofacial skeleton. Plagiocephaly is only a subform of the syndrome. The
      deformity progresses unless operative treatment is given. Operative treatment is
      indicated for functional, aesthetic, and psychosocial reasons. We advocate early
      operation in infancy (3 to 6 months) consisting of wide resection of the stenosed
      sutures of the cranium and orbit, repositioning, and remodeling relying on the
      spontaneous autodynamic reshaping of the nasoethmoidal complex and the midface
      structures during the course of further growth. In adolescents and adults,
      multisegmental osteotomies and remodeling into a definitive position are
      necessary.

PMID- 1994813
TI  - Running Y-V plasty.
AB  - Problems in treating burn sequelae include scar tissue contraction, which may
      develop after wound infections, after secondary wound healing by granulations,
      and also after split-skin transplants. Development of scar cords near or even
      over joints can ultimately lead to deformities of the body and limbs because of
      restriction of mobility. Compression bandages have the goal of counteracting
      these problems, but are not always effective. An attempt must be made to resect
      the scar cords and to cover the defect with skin transplants or to change the
      line of the scar cord with Z plasties. However, the altered blood flow in the
      nodularly twisted collagen fiber structure of the hypertrophic scar frequently
      causes the tips of transposed skin flaps (as, for example, in Z plasties) to
      become necrotic. This situation is avoided by application of Y-V plasties, in
      which the skin for transposition is not detached from its substratum (in contrast
      to the Z plasty) but is displaced by sliding it on its substratum. For this
      purpose, the tension of the scar cord is eliminated over the entire length by
      several transverse Y-shaped incisions situated in parallel. If the tongues of the
      upper part slide into the stem of the Y and finally from a V, the scar cord can
      be lengthened without raising the dermis from it substratum and endangering its
      blood flow. Because of good results, Y-V plasty has entirely replaced Z plasty in
      the correction of contracted burn scars at my hospital.

PMID- 1994814
TI  - PMMA microspheres for intradermal implantation: Part I. Animal research.
AB  - In search of a biocompatible implant for the correction of small deficiencies
      within the dermal corium as in wrinkles and acne scars, polymethylmethacrylate
      (PMMA) microspheres, 10 to 63 microns in diameter, were dispersed in Tween 80
      medium and injected intradermally and subdermally into the abdominal skin of
      rats. Histological examination of specimens for up to 7 months revealed a modest
      tissue reaction, forming a delicate fibrous capsule around each individual
      microsphere within 4 months. Foreign body giant cells were seen rarely (in up to
      1.5% of all cells). No break-down, corrosion, or phagocytosis of the spheres was
      observed at 7 months. The Tween 80 dispersion medium did not produce any
      histologically detectable reaction. Because PMMA products (Paladon, Palacos) have
      been used in medicine for almost 50 years without causing biological degradation
      or cancer, the material may be applied safely in the form of microspheres
      (Arteplast) in corium and subcutis of human patients with wrinkles or acne scars.

PMID- 1994815
TI  - The V flap: a combination of V-Y advancement and two Limberg transposition flaps.
AB  - Two annoying problems are encountered in surgical correction of greater defects
      by flap plasty: the widely undermined cavity seen when using transposition flaps
      to cover large wound cavities and the necessity to cut away healthy skin because
      of dog ears or a Burrow's triangle. The V flap is a method of shifting and
      transposing of the skin surrounding the defect to avoid these troublesome
      disadvantages. With the exception of cases where a myocutaneous island flap is
      indicated, this simple V-flap technique yields excellent surgical results.

PMID- 1994816
TI  - Brachial plexus injuries: an integrated treatment concept.
AB  - An integrated concept is presented for the treatment of lesions of the brachial
      plexus. In such patients, nerve repair is useless as a single method of therapy.
      Only the combination of nerve repair with both conventional and new methods of
      muscle and tendon transfer, including the free muscle transplant innervated by
      vascularized nerve grafts, can give the patient functional use of the paralyzed
      arm.

PMID- 1994818
TI  - More arguments in favor of myocutaneous flaps for the treatment of pelvic
      pressure sores.
AB  - The use of myocutaneous flaps for the treatment of pelvic pressure sores is well
      accepted, yet there are still unanswered questions about why myocutaneous flaps
      are clinically superior to skin flaps. An experiment involving 16 pigs revealed
      new data on the diffusion of infection through myocutaneous and cutaneous flaps,
      showing that the muscles can act as a barrier against such infection. In 51
      patients seen consecutively in 1988, osseous specimens of the infected bottom of
      the decubital ulcers were taken. There was florid osteomyelitis in 65.9% of all
      specimens, further emphasizing the importance of muscle flaps in the treatment of
      pelvic pressure sores when infection is still present. The fate of 16 transposed
      gluteus maximus muscles was monitored by electromyography postoperatively; 15
      still showed voluntomotoricity up to 7 months after transposition.

PMID- 1994817
TI  - Ischemic tolerance of human skeletal muscle.
AB  - Until now, the ischemic tolerance of muscle tissue has not been adequately
      understood. Even when muscle vitality is lost, the perfusion matrix of the muscle
      flaps is retained. Because of toxic decomposition, however, irreversibly damaged
      muscle cells almost certainly increase the rate of complications. The retention
      of the vitality of the transplanted muscle tissue is absolutely essential for the
      myokinetic substitute operations, currently in the development stage, involving
      the free transplantation of muscles. Investigations into vitality reserves were
      carried out on skeletal muscle specimens. Nuclear magnetic resonance spectroscopy
      was used to establish that, in ischemia, the ATP pool remained topped up to a
      large extent as long as phosphocreatine was available. As long as the ATP pool
      was retained, rearterialization led to the complete restoration of the essential
      preischemic metabolite concentrations. After the ATP had been exhausted,
      biochemical restitution through arterial reperfusion did not occur. The time by
      which the established vitality threshold was reached because of the loss of the
      ATP pool is called the critical ischemia time; it depends on muscle temperature.
      The critical ischemia time of human skeletal muscles was determined between 26
      degrees and 38 degrees C. A normothermia of 34 degrees C yielded a critical
      ischemia time of 2.25 hours, which is shorter than that previously reported in
      the literature. An ischemic tolerance of 5 hours presupposes a muscle temperature
      of less than 26 degrees C.

PMID- 1994819
TI  - Skin banking: a simple method for cryopreservation of split-thickness skin and
      cultured human epidermal keratinocytes.
AB  - A simple unit has been developed for the simultaneous passive cooling of small
      and large amounts of allograft or autograft split-thickness skin, as well as
      cultured human epidermis. An expanded polystyrene box of variable size, aluminum
      plates, and cellulose tissue are fused. This unit is cooled in a -70 degrees C
      constant-temperature mechanical refrigerator. Maximal cooling rates of -1.3
      degrees C min-1 are obtained in a box with a constant wall thickness of cellulose
      tissue. The cooling rate can be varied by altering the number of cellulose
      layers. Exothermic temperature plateaus associated with skin cooled in this unit
      last for less than 0.3 minutes. The viability of the cryopreserved skin was
      determined by using up to four methods simultaneously: a dye-exclusion test with
      trypan blue; glucose consumption; production of lactate; and carbon-13 nuclear
      magnetic resonance spectroscopy. Using a cryoprotectant medium with 15% (vol/vol)
      glycerol for split-thickness skin 0.25 mm thick, a storage time of up to 509 days
      at -70 degrees C was observed, with only a small decrease in viability (trypan
      blue, 62.5%; glucose consumption, 71 to 90% compared with freshly harvested
      skin). Storage in liquid nitrogen did not significantly improve results (p
      greater than 0.05).

PMID- 1994820
TI  - Immediate breast reconstruction using an external oblique rectus musculofascial
      turnover flap.
AB  - The development of the external oblique rectus musculofascial turnover flap has
      recently received a great deal of attention. With this method, the upper part of
      the external oblique muscle is lifted off the lower thoracic wall along with a
      segment of the rectus muscle, pedicled in the sixth intercostal space and
      subsequently connected with the lower margin of the pectoralis major muscle. This
      approach bridges the weak regions of the thin muscle layers in the medioinferior
      breast area. Because this procedure avoids the need for a second operation to
      restore the contour and enables production of a natural ptosis and a well
      accentuated lower breast fold, it has become increasingly important in immediate
      breast reconstruction. Compared with the complex myocutaneous flaps techniques,
      this procedure is characterized by relative simplicity and ease of performance.
      Compared with the tissue expansion technique, the oblique rectus turnover flap
      allows restoration of the female form in a one-stage procedure with a better,
      more natural ptotic breast shape and well-defined inframammary crease. Results
      have been encouraging. In fact, this procedure has almost completely replaced
      other techniques for immediate reconstruction of the female breast following
      mastectomy.

PMID- 1994822
TI  - Is the National Practitioner Data Bank a boon to public safety or Big Brother in
      disguise?

PMID- 1994821
TI  - Coordinating clinical research. A collaborative approach for perioperative
      nurses.
AB  - Overall, the study progressed smoothly during the six months it took to collect
      data on 125 patients. A number of factors contributed to the success of the
      study. By using a collaborative approach, we assembled a team with expertise in
      the content area, the clinical setting, and research design and methodology. This
      diverse mixture of knowledge, experience, and skills enabled us to plan carefully
      and anticipate many problems when writing the proposal and designing the study.
      While planning and implementing the study, we made an effort to keep
      communication flowing at all levels so problems could be quickly detected and
      addressed. We worked from the premise that we were collaborating with all of the
      OR nursing staff. We tried to use their time wisely, give them a meaningful role,
      respect their other responsibilities and commitments, and provide them with
      opportunities to share in the positive feelings that come from successfully
      completing a difficult job. We believe we achieved some measure of success. Since
      finishing the study, many staff members expressed an interest in participating in
      future studies--a good indication that they find research less formidable. They
      view participation in studies as a way to progress through the clinical ladder
      system and realize a full professional role. Most importantly, they see
      participating in research as a way to improve the quality of patient care they
      provide.

PMID- 1994823
TI  - Recruitment and retention. Strategies for keeping good nurses.

PMID- 1994824
TI  - Proposed recommended practices. Documentation of perioperative nursing care. AORN
      Recommended Practices Coordinating Committee.

PMID- 1994825
TI  - Pain management for the elderly: alternative interventions (Part II).

PMID- 1994826
TI  - Testimonial to using universal precautions.

PMID- 1994827
TI  - The nurse/physician relationship and ethical decision making.

PMID- 1994828
TI  - Safe administration of midazolam.

PMID- 1994829
TI  - Surviving traumatic head injury requires support.

PMID- 1994830
TI  - Coronary atherectomy. An alternative to balloon angioplasty.
AB  - To date, physicians at our hospital have performed coronary atherectomy on 15
      patients. Of these patients, four needed open heart surgery. One patient needed
      surgery because a vessel was dissected during the procedure, and the three other
      patients had unsuccessful procedures. One patient died due to a cerebrovascular
      bleed related to the anticoagulation therapy required for the procedure. Of the
      remaining patients, three had no reocclusion and four had reocclusion at their
      six-month follow-up examinations. The remaining patients have not had a six-month
      follow-up examination. The restenosis rate at our institution is 25%. It is hoped
      that catheter-mediated atherectomy will be an effective, predictable transluminal
      treatment of single or multiple focal stenosis. Because of the small patient
      sampling and short duration follow-up, no trends have been established. A six
      month follow-up with angiography will establish patency and restenosis rates.

PMID- 1994831
TI  - Retroperitoneal approach to abdominal aortic aneurysm. Positive outcomes for
      patient and nurse.

PMID- 1994832
TI  - Vocal cord paralysis. Treatment with Teflon paste injections.
AB  - The immediate restoration of laryngeal function in patients suffering unilateral
      vocal cord paralysis after major thoracic vascular procedures makes the use of
      Teflon paste injection a desirable treatment. It is safe, effective, and simple
      when performed by an experienced surgeon and OR team.

PMID- 1994833
TI  - Patent ductus arteriosus ligation. Performing surgery outside the operating room.

PMID- 1994834
TI  - The samurai and the tea master show us the meaning of excellence.

PMID- 1994835
TI  - Outpatient surgery documentation. Incorporating nursing diagnoses.

PMID- 1994836
TI  - Baby Check: a scoring system to grade the severity of acute systemic illness in
      babies under 6 months old.
AB  - A scoring system has been developed to grade the severity of acute systemic
      illness in babies under 6 months of age. Data were collected on 28 symptoms and
      47 signs from 1007 babies with a spectrum of illness ranging from well to
      seriously ill. Ordinal regression analysis identified 19 symptoms and signs which
      in combination graded the severity of the illness most accurately. The
      coefficients were converted to scores. The higher the score the more serious the
      illness. When applied to a theoretical cohort of 10,000 babies at home, a score
      less than 8 has a specificity of 98%, and a score of 13 or more a sensitivity of
      92%. The positive predictive value for serious illness increases from zero at a
      score of zero to approaching 100% at scores over 30. The scoring system has been
      developed into score cards for parents and professionals.

PMID- 1994837
TI  - Field trials of the Baby Check score card: mothers scoring their babies at home.
AB  - The Baby Check score card has been developed to help parents and health
      professionals grade the severity of acute illness in babies. This paper reports
      the results of two field trials in which mothers used Baby Check at home, 104
      mothers scoring their babies daily for a week and 56 using it for six months.
      They all found Baby Check easy to use, between 68% and 81% found it useful, and
      96% would recommended it to others. Over 70% of those using it daily used it very
      competently. Those using it infrequently did less well, suggesting that
      familiarity with the assessment is important. The scores obtained show that Baby
      Check's use would not increase the number of mothers seeking medical advice. With
      introduction and practice most mothers should be able to use Baby Check
      effectively. It should help them assess their babies' illnesses and make
      appropriate decisions about seeking medical advice.

PMID- 1994838
TI  - Field trials of the Baby Check score card in general practice.
AB  - Sixteen general practitioners (GPs) used the Baby Check score card to assess
      illness severity in 86 babies under 6 months old. Their reactions to Baby Check
      were positive: in 79 (92%) it gave an accurate assessment of the baby's illness
      and 16 (100%) said they would trust it. Fifteen (94%) found it useful, and most
      of those who did not said the baby was not ill or had an obvious diagnosis.
      Thirteen (81%) said they would use it and wanted their health visitors and
      midwives to use it and 15 (94%) wanted the mothers in their practice to use it.
      The majority (64%) of babies scored 0-7; 31% scored 8 to 19; and only 5% scored
      over 20. Well babies had low scores, while the two sickest babies, needing urgent
      hospital treatment, scored 29 and 33. The use of Baby Check by GPs would help
      them assess babies thoroughly and quantify illness severity objectively.

PMID- 1994839
TI  - Field trials of the Baby Check score card in hospital.
AB  - The Baby Check score card was used by junior paediatric doctors to assess 262
      babies under 6 months old presenting to hospital. The duty registrar and two
      consultants independently graded the severity of each baby's illness without
      knowledge of the Baby Check score. The registrars assessed the babies at
      presentation while the consultants reviewed the notes. The consultants and
      registrars agreed about the need for hospital admission only about 75% of the
      time. The score's sensitivity and predictive values were similar to those of the
      registrars' grading. The score's specificity was 87%. Babies with serious
      diagnosis scored high, while minor illnesses scored low. The predictive value for
      requiring hospital admission increased with the score, rising to 100% for scores
      of 20 or more. The appropriate use of Baby Check should improve the detection of
      serious illness. It could also reduce the number of babies admitted with minor
      illness, without putting them at increased risk.

PMID- 1994840
TI  - Endoscopic retrograde cholangiopancreatography in infantile cholestasis.
AB  - The difficulty of distinguishing surgically correctable causes of conjugated
      hyperbilirubinaemia in infants from other causes means that some infants may
      undergo laparotomy and intraoperative cholangiography unnecessarily, and others
      may be referred for surgery too late. In an attempt to improve the diagnostic
      accuracy in infants with conjugated hyperbilirubinaemia when standard methods
      produced equivocal results, we have been using prototype paediatric duodenoscopes
      (PJF 7.5 and XPJF 8.0; Olympus) to perform endoscopic retrograde
      cholangiopancreatography (ERCP). From 159 infants with conjugated
      hyperbilirubinaemia, 11 were referred for ERCP, which was performed in nine. In
      four in whom bile ducts were definitely visualised laparotomy was avoided.
      Operative cholangiography confirmed patent bile ducts in one in whom
      visualisation had been uncertain. Three of four in whom bile ducts were not seen
      had extrahepatic biliary atresia. Visible bile drainage in the fourth excluded
      atresia. No major complications ensued but there was radiological evidence of
      gall bladder perforation in one (common hepatic duct block) and overinflation
      with air was a problem until finer cannulae (Wilson-Cook) were introduced. In
      appropriately selected patients with conjugated hyperbilirubinaemia, ERCP with
      paediatric duodenoscopes in experienced hands may provide useful diagnostic
      information.

PMID- 1994841
TI  - Audit of results of operations for infantile pyloric stenosis in a district
      general hospital.
AB  - Because of the proposal that infants with hypertrophic pyloric stenosis should
      only be treated by surgeons with an interest in paediatric surgery, we carried
      out a retrospective study to audit our experience in a district general hospital.
      Forty six infants over a five year period underwent pyloromyotomy. There were no
      deaths, and 36 infants (78%) made uneventful recoveries. Perforation of the
      duodenal mucosa occurred during the operation in 11 patients, and eight
      complications developed in six of these infants. There were seven wound
      infections, and two patients had vomiting that lasted four days or longer after
      their operations. There were no long term feeding problems. The results of this
      study show that such patients can be successfully treated in district general
      hospitals, and three areas merit special attention: meticulous surgical
      technique, the use of prophylactic antibiotics, and early graduated feeding.

PMID- 1994843
TI  - Orocaecal transit time in Duchenne muscular dystrophy.
AB  - Smooth muscle degeneration may occur in Duchenne muscular dystrophy. We measured
      fasting orocaecal transit time in patients with advanced Duchenne muscular
      dystrophy and other muscular dystrophies and in healthy controls. No significant
      differences were found. In contrast to reports of gastric hypomotility in
      Duchenne muscular dystrophy, we found no evidence of impaired small intestinal
      motility.

PMID- 1994842
TI  - Longitudinal study of cholesterol values in 68 children from birth to 11 years of
      age.
AB  - Sixty eight children born in 1977 who were taking part in an unrelated study of
      childhood asthma were selected to have their serum cholesterol concentrations
      measured at birth, and at 4 months and 1, 2, 3, 4, 5, and 11 years of age.
      Concentrations of high density lipoprotein were measured at 5 and 11 years.
      Cholesterol values increased rapidly from birth and plateaued at 1 year. There
      was a further small rise just before puberty. Tracking of values was seen after
      the age of 1 year, but did not become established until 4 years of age. The
      cholesterol concentrations in girls were marginally higher than those in boys.
      The mean (SD) values of cholesterol (mmol/l) for boys were: at birth, 1.7 (0.4);
      at 1 year, 3.9 (0.9); at 5 years, 5.2 (1.9); and at 11 years, 5.0 (0.7). For
      girls the corresponding figures were; at birth, 1.9 (0.6); at 1 year, 4.7 (1.0);
      at 5 years, 4.6 (0.7); and at 11 years, 5.1 (0.7). The mean (SD) high density
      lipoprotein concentrations (mmol/l) for boys were: at 5, 1.16 (0.35) and at 11,
      1.51 (0.23). For girls they were 1.28 (0.30) and 1.56 (0.27), respectively. The
      serum cholesterol concentrations in these children were high compared with
      published figures from north America.

PMID- 1994844
TI  - Effects of maternal iodine supplementation during pregnancy.
AB  - Reduced maternal thyroid hormone concentrations during pregnancy can adversely
      affect fetal neurological development. In the context of national iodine
      supplementation programmes, concern has been expressed over the theoretical
      possibility that iodine supplementation during pregnancy might adversely affect
      fetal development as a result of maternal thyroid inhibition from the Wolff
      Chaikoff effect. In a double blind controlled trial in five villages in Papua New
      Guinea, several measures of motor and cognitive function showed no significant
      differences at either age 11 or 15 years between those children whose mothers had
      received supplementary iodine during pregnancy and the control children whose
      mothers had received the placebo.

PMID- 1994845
TI  - Bleeding from duodenal lymphangiectasia.
AB  - An 8 year old girl with recurrent upper gastrointestinal bleeding was found to
      have localised duodenal lymphangiectasia by fibreoptic endoscopy. She did not
      show physical signs or laboratory evidence of significant enteric protein loss. A
      low fat diet seemed to prevent further bleeding. Duodenal lymphangiectasia may be
      associated with gastrointestinal bleeding in children.

PMID- 1994846
TI  - Cardiac echinococcosis with fatal intracerebral embolism.
AB  - A previously well 7 year old boy presented with sudden loss of consciousness and
      fitting. No evidence of trauma or space occupying lesion was identified. Death
      occurred the next day due to cerebral infarction caused by embolised fragments
      from a ruptured left ventricular hydatid cyst that was found at necropsy.

PMID- 1994847
TI  - Effect of the new GP contract on child health clinics.

PMID- 1994848
TI  - Child health clinics.

PMID- 1994849
TI  - European paediatrics--unity with diversity?

PMID- 1994850
TI  - Antibiotic treatment of suspected neonatal meningitis.

PMID- 1994851
TI  - Effective bronchodilator treatment by a simple spacer device for wheezy premature
      infants.

PMID- 1994852
TI  - Gender and the progression of Escherichia coli O157:H7 enteritis to haemolytic
      uraemic syndrome.

PMID- 1994853
TI  - Ready, steady, hiss.

PMID- 1994854
TI  - Reflux vomiting.

PMID- 1994855
TI  - Terminology in community child health.

PMID- 1994856
TI  - Use of peripheral vessels for exchange transfusion.

PMID- 1994857
TI  - Respiratory rate and pneumonia in infancy.

PMID- 1994858
TI  - Tests for growth hormone secretion.

PMID- 1994859
TI  - Ethnic differences in infant health.

PMID- 1994860
TI  - Elemental diet for refractory atopic eczema.
AB  - A total of 37 children with refractory wide-spread atopic eczema were treated
      with an antigen avoidance regimen comprising hospitalisation, exclusive feeding
      with an elemental formula for a median duration of 30 days, and measures to
      reduce exposure to pet and dust mite antigens at home. After the initial period
      of food exclusion, food challenges were performed at intervals of seven days, and
      the patients followed up for at least 12 months. Ten of the children (27%) either
      failed to respond to the regimen or relapsed within 12 months. Improvement in the
      eczema was seen in 27/37 (73%) patients, by discharge from hospital their disease
      severity score had fallen to a median of 27% of the pretreatment figure, and only
      3/27 required topical corticosteroids. There were no clinical or laboratory
      findings which could be used to predict the outcome. Drawbacks to the regimen
      were prolonged hospitalisation (median 70 days), a fall in body weight and serum
      albumin concentration, and a risk of anaphylactic shock (4/37 cases). A strict
      antigen avoidance regimen may be associated with improvement of atopic eczema
      where conventional treatments have failed.

PMID- 1994861
TI  - Magnetic resonance imaging in osteoarthritis of the knee: correlation with
      radiographic and scintigraphic findings.
AB  - Twelve knees with a range of severity of knee osteoarthritis were assessed by
      magnetic resonance imaging (MRI) and technetium-99m labelled hydroxymethylene
      diphosphonate scintigraphy. Five magnetic resonance pulse sequences were
      evaluated. Proton density (TR = 1000, TE = 26 ms) and STIR (TR = 1500, TI = 100,
      TE = 30 ms) were chosen for further use. Abnormalities shown by MRI included
      joint effusions, meniscal disruption, hyaline cartilage thinning, subchondral
      signal changes, pseudocysts, and heterogeneity of signal from osteophytes.
      Certain MRI and scintigraphic appearances correlated: (a) 'hyperintense
      osteophytosis' and ipsilateral 'tramline' scintigraphic uptake, suggesting
      increased fat content in 'active' osteophytes; (b) subchondral signal change and
      'extended' pattern, possibly reflecting inflammation, synovial leak, or
      fibrovascular repair; (c) patellofemoral joint signal changes and patellar
      isotope uptake.

PMID- 1994862
TI  - Pattern of osteoarthritis in a West African teaching hospital.
AB  - The study of the pattern of osteoarthritis in different populations may yield
      valuable aetiological clues and also allow subtypes to be defined. Over one year
      252 osteoarthritic joints from 140 patients seen at a West African teaching
      hospital were prospectively reviewed. The knee was the joint most often affected.
      Hip and hand disease, as well as Heberden's nodes, were uncommon. Joint disease
      was predominantly monoarticular; no patient had three or more sites affected.

PMID- 1994864
TI  - Production of intracellular and extracellular interleukin-1 alpha and interleukin
      1 beta by peripheral blood monocytes from patients with connective tissue
      diseases.
AB  - An enzyme linked immunosorbent assay (ELISA) was used to estimate the production
      of intracellular and extracellular interleukin-1 (IL-1) alpha and beta by
      peripheral blood monocytes from 26 patients with various connective tissue
      diseases (CTD), including 19 with systemic lupus erythematosus, four with
      progressive systemic sclerosis, two with mixed connective tissue disease, and one
      with Sjogren's syndrome. Monocytes obtained from patients with CTD with serum
      antibodies to nuclear ribonucleoprotein (nRNP) released significantly higher
      concentrations of extracellular IL-1 alpha and IL-1 beta, whereas intracellular
      IL-1 alpha and IL-1 beta production was similar to that by monocytes from
      patients with CTD without antibodies to nRNP. Furthermore, the concentrations of
      extracellular IL-1 alpha correlated significantly with those of extracellular IL
      1 beta. There was no significant correlation between the concentrations of
      extracellular and intracellular IL-1 alpha, and those of extracellular and
      intracellular IL-1 beta, indicating that synthesis and secretion of IL-1 by human
      monocytes may be two distinct biological events. It seems that enhanced
      extracellular release of both IL-1 alpha and IL-1 beta contributes to the
      excessive anti-nRNP production in CTD.

PMID- 1994863
TI  - Osteoarticular complications of brucellosis.
AB  - Two hundred and sixty three patients with a diagnosis of brucellosis between
      January 1984 and December 1987 were studied prospectively. Sixty five patients
      (25%) developed osteoarticular complications. These patients had a more prolonged
      course than those with no complications. Spondylitis in 38 (58%) and sacroiliitis
      in 29 (45%) were the most prevalent. There were no significant laboratory,
      serological, or bacteriological differences between patients with and without
      osteoarticular complications. At diagnosis 47 patients (72%) showed radiographic
      abnormalities, commonly in axial sites but rarely in peripheral sites.
      Radionuclide bone scan was positive with no radiographic abnormalities in 17
      (26%) of cases. Fifty seven patients received medical treatment alone, 51 (89%)
      being cured with a single course of treatment. Treatment failed or there was a
      relapse in six patients (11%), of whom five had spondylitis. Eight of the 65
      patients (12%), all of whom had spondylitis and paravertebral or epidural
      abscesses, also required surgical treatment.

PMID- 1994865
TI  - Population projections and the effect on rheumatology.

PMID- 1994866
TI  - Bronchial hyperresponsiveness to methacholine in patients with primary Sjogren's
      syndrome.
AB  - The prevalence of bronchial hyperresponsiveness (BHR) to methacholine inhalation
      in a consecutive series of 21 patients with primary Sjogren's syndrome was
      studied prospectively. Slight to severe BHR was seen in 12/20 (60%) of the
      patients. Ten of 12 patients with BHR (83%) had a non-productive cough, wheezing,
      or intermittent breathlessness. Bronchial hyperresponsiveness was more common in
      patients with extraglandular symptoms (10/14, 71%) than in those with only
      glandular symptoms (29%). Spirometrically 29% (6/21) of the patients had 'small
      airways' disease', and all those had BHR. Of 6/21 (29%) who had diffuse
      interstitial lung disease, two had BHR. Three of the four patients with
      obstructive lung function were challenged with methacholine and two of them had
      BHR. Only two patients with BHR had normal spirometry findings. The data showed
      that respiratory disease--mostly mild or moderate but even severe bronchial
      hyperresponsiveness--is commonly seen in patients with primary Sjogren's
      syndrome.

PMID- 1994868
TI  - Muscle cramps in the calf as presenting symptom of sarcoidosis.
AB  - A patient is described, who presented with pain in the calf due to a palpable
      nodule as the presenting symptom of sarcoidosis. The patient was treated with
      rest and diclofenac, followed by intralesional injections with triamcinolone
      hexacetonide and became free from pain.

PMID- 1994867
TI  - A controlled study of stanozolol in primary Raynaud's phenomenon and systemic
      sclerosis.
AB  - A double blind, crossover study of fibrinolytic enhancement treatment using
      stanozolol has been performed in primary Raynaud's phenomenon and in systemic
      sclerosis. The outcome criteria included subjective evaluation, clinical
      examination, physiological measurements of peripheral blood flow, and
      fibrinolytic measurements. Nineteen patients entered and 11 completed the study
      of primary Raynaud's phenomenon. There was nonsignificant evidence of improvement
      in peripheral blood flow. Twenty four patients entered and 17 completed the study
      of systemic sclerosis. There was marked objective but not subjective evidence of
      improvement in the peripheral microcirculation during the stanozolol treatment
      period. There was also a nonsignificant improvement in dermal sclerosis. There
      were improvements in fibrinolytic activity during the stanozolol treatment
      period. There was no alteration in fibrinolytic reserve as measured by 1-desamino
      8-D-arginine vasopressin stimulation, however. Although adverse events were
      common in both treatment periods, withdrawals predominantly occurred during the
      period of treatment with stanozolol and were principally due to anabolic
      problems. There does not seem to be any indication for the use of stanozolol in
      primary Raynaud's phenomenon. Fibrinolytic enhancement with stanozolol does
      appear useful in treating the microvascular features of systemic sclerosis.

PMID- 1994869
TI  - Palmar fasciitis and arthritis in a patient with an extraovarian adenocarcinoma
      of the coelomic epithelium.
AB  - A 54 year old woman presented with an intra-abdominal adenocarcinoma of primary
      coelomic origin and a syndrome of palmar fasciitis and arthritis, which was
      exacerbated during treatment by combination chemotherapy with intravenous
      carboplatin 300 mg/m2 and cyclophosphamide 750 mg/m2, while the tumour responded
      well.

PMID- 1994870
TI  - Eosinophilic fasciitis associated with L-tryptophan ingestion.
AB  - A 62 year old woman taking L-tryptophan developed eosinophilic fasciitis shortly
      after starting an exercise class. She received prednisone without benefit but
      improved after azathioprine treatment was started and L-tryptophan was
      discontinued. As products containing L-tryptophan have recently been implicated
      in development of the eosinophilia-myalgia syndrome it is suggested that the use
      of L-tryptophan might have contributed to the development of eosinophilic
      fasciitis in this patient. Similarities with toxic oil syndrome are noted.
      Additional studies are warranted to determine the prevalence of L-tryptophan
      ingestion among patients diagnosed as having eosinophilic fasciitis.

PMID- 1994872
TI  - Do you need to write a thesis?

PMID- 1994871
TI  - Degradation of human cartilage by synovial fluid but not cytokines in vitro.
AB  - Synovial fluids from patients with rheumatoid arthritis and from patients with
      osteoarthritis degraded the matrix of living, but not killed, normal human
      cartilage as judged by loss of glycosaminoglycans. Normal human serum did not
      degrade living cartilage and neither, unexpectedly, did recombinant human
      cytokines.

PMID- 1994873
TI  - The familial nature of rheumatoid arthritis.

PMID- 1994874
TI  - Brown's syndrome: an unusual ocular complication of rheumatoid arthritis.

PMID- 1994875
TI  - Pulsed methylprednisolone therapy in rheumatoid arthritis.

PMID- 1994876
TI  - Bilateral pseudothrombophlebitis.

PMID- 1994877
TI  - Study of 500 patients with limb joint osteoarthritis. I. Analysis by age, sex,
      and distribution of symptomatic joint sites.
AB  - Five hundred subjects with symptomatic limb joint osteoarthritis, who had been
      referred to a rheumatologist, were enrolled into a continuing study. They
      comprised 342 women (mean age 65.3) and 158 men (mean age 59.7), with a mean
      symptom duration of 15.4 years at entry. Only 31 patients (6%) had symptomatic
      osteoarthritis of one joint alone; however, in a further 205 (41%) the disease
      was limited to one site. One hundred and eighty two (36.4%) had two sites
      affected and 82 (16.4%) three or more sites of symptomatic osteoarthritis. Of 847
      affected joints the most commonly involved were 349 (41.2%) knees, 254 (30%)
      hands, and 161 (19%) hips. Hip disease stood out as a separate entity, often
      occurring alone, and having a stronger male preponderance and different
      associations than osteoarthritis at other joint sites. Knee and hand disease were
      significantly associated in women. Obesity, hypertension, and Heberden's nodes
      were common. The number of sites affected, as well as the distribution, was
      strongly related to age as well as sex, suggesting that polyarticular
      osteoarthritis arises from slow acquisition of new joint sites in a non-random
      distribution. 'Generalised' osteoarthritis did not emerge as a distinct entity.

PMID- 1994878
TI  - Adjuvant therapy of colorectal cancer: an overview.
AB  - The substantial recurrence rate of colorectal cancer following potentially
      curative resection has fuelled the search for effective adjuvant therapy.
      Previous trials using 5-fluorouracil (5-FU) as a single agent or in combination
      chemotherapy regimens have not demonstrated meaningful benefits, an impression
      reflected in the results of a meta-analysis encompassing large patient numbers.
      Newer developments utilizing intraportal chemotherapy and the combination of 5-FU
      and levamisole have resulted in lower recurrence rates and improved survival in
      patients with colon cancer. In advanced disease, the biochemical modulation of 5
      FU by Leucovorin has been shown to prolong survival in some studies. Combined
      chemotherapy and radiotherapy or chemotherapy alone have showed promising results
      in rectal cancer. These developments have now been incorporated into ongoing
      trials.

PMID- 1994879
TI  - Adjuvant therapy for patients with colon and rectal cancer: summary of NIH
      consensus statement. National Cancer Institute and the Office of Medical
      Applications of Research of the National Institutes of Health.

PMID- 1994880
TI  - Peri-operative colonoscopy detects synchronous tumours in patients with
      colorectal cancers.
AB  - The aim of this study was to assess the value of colonoscopy as a peri-operative
      investigation in patients treated for colorectal cancer by surgical excision.
      Patients (134 male, 83 female) undergoing curative resection for colorectal
      carcinoma between August 1984 and January 1989 had colonoscopy within 3 months of
      surgery. Eleven patients (5%) had a synchronous cancer, which was diagnosed by
      colonoscopy in eight. In six of these eight, the diagnosis was made after surgery
      and 3 patients needed a second colectomy. However, in 3 patients the synchronous
      cancer was removed endoscopically without the need for further surgical
      resection. Most synchronous cancers had an earlier pathological stage than the
      index tumour. The rate of synchronous cancers was higher in patients with
      synchronous benign polyps (16%) than in those without polyps (3%). Colonoscopy is
      clearly justified as a peri-operative investigation in all patients undergoing
      potentially curative resection of colorectal cancer. If possible, the examination
      should be carried out prior to surgery, to guide the extent of resection.

PMID- 1994881
TI  - A survey of antimicrobial prophylaxis in elective colorectal surgery in New
      Zealand.
AB  - In 1988 a survey of New Zealand general surgeons was conducted, by post, on the
      subject of routine antimicrobial prophylaxis for elective colorectal surgery.
      Surgeons who gave routine prophylaxis were asked for details of their regimens;
      those who did not were asked for their reasons. One hundred and seventy-five
      questionnaires were distributed and 167 were returned. Of these, 124 came from
      surgeons with a colorectal practice, and 118 of the 124 surgeons satisfactorily
      completed the questionnaire. Routine antimicrobial prophylaxis was given by 96.6%
      (114 of 118). Of the 114 surgeons prescribing prophylaxis, one antimicrobial
      agent was used by 36.8%, two were employed by 53.5% and three or five were used
      by the remainder. The most commonly used (74.6%) antimicrobial agents were
      cephalosporins which were prescribed, alone or in combination with a
      nitroimidazole. The most frequent duration (46.4%) of antimicrobial
      administration was a combination of both the peri- and postoperative periods.
      When antimicrobial spectrum, route and duration of administration were all taken
      into account, 49.1% (56 of 114) were considered to give satisfactory regimens.
      Excessively protracted administration was the most frequent reason for
      unsatisfactory classification. The results of this survey demonstrate serious
      deficiencies in the practice of antimicrobial prophylaxis in elective colorectal
      surgery. These should be addressed through a programme of continuing education.

PMID- 1994882
TI  - Adjuvant therapy in bowel cancer: its time has arrived.

PMID- 1994883
TI  - Toothpick injuries to the gastrointestinal tract.
AB  - Perforation of the gastrointestinal tract by toothpicks is an uncommon but well
      described occurrence. Five cases treated by the authors over the past 5 years are
      described. This series emphasizes the fact that plain abdominal and chest
      radiology is unhelpful in establishing the diagnosis. Risk factors identified are
      the wearing of dentures and previous abdominal surgery.

PMID- 1994884
TI  - Achalasia of the oesophagus: results of treatment.
AB  - Achalasia of the oesophagus is an uncommon neuromuscular disorder characterized
      by symptoms of dysphagia and regurgitation of undigested food. The results of
      treatment of 43 patients with achalasia over 10 years are presented. Clinical
      data on presenting complaints and duration, and all subsequent treatments, were
      recorded. Patients were contacted to assess their current symptomatic status.

PMID- 1994885
TI  - Effect of hepatic cryotherapy on serum CEA concentration in patients with
      multiple inoperable hepatic metastases from colorectal cancer.
AB  - Eleven patients with multiple hepatic metastases from colorectal cancer, all
      judged inoperable, were treated by cryotherapy using a probe through which liquid
      nitrogen was circulated using a single freeze thaw sequence. Localization of
      metastases, positioning of the probe and monitoring of ice ball size was by intra
      operative ultrasound. Serum carcinoembryonic antigen (CEA) was measured in these
      patients: there was a postoperative fall in all but two. In all but one, there
      has been a subsequent rise. Speed and degree of rise of CEA varied between
      patients. Serial CEA may be an effective means of monitoring the effect of
      hepatic cryotherapy.

PMID- 1994886
TI  - Intra-operative colonic lavage: safe single-stage, left colorectal resections.
AB  - Fifty consecutive left-sided colorectal cases are described in which intra
      operative colonic lavage (IOCL) was used. Sixteen were acute or sub-acute cases,
      including five with total colonic obstruction. The anastomoses were usually hand
      sutured and no colostomies were used: all procedures were single stage. Only one
      case was considered to have possibly had an anastomotic leak (2.0%) and the
      average hospital stay was 16 days. There were 3 wound infections (6%). Peri
      operative mortality was 6% and no deaths occurred in the acute or sub-acute
      cases. The procedure allows safe one-stage operation in most acute left-sided
      colonic lesions and provides the most thorough colonic preparation for elective
      cases, thus obviating the need for colostomy in cases where the colon is found to
      be inadequately prepared, or in very low anastomoses. The technique described for
      IOCL is readily reproduced, attendant with negligible risk of complications and
      takes relatively little extra operating time. Defunctioning colostomy is unlikely
      to be necessary with this method, thereby saving patients considerable discomfort
      and nuisance, time in hospital and the potential morbidity of further operation.
      Specific recommendations for use of IOCL are: acute or sub-acute left colonic
      obstruction: stenosing or volvulus; massive colonic haemorrhage: for diagnostic
      and preparatory use; rectal and left colonic trauma; left colonic surgery where
      inadequate pre-operative bowel preparation has occurred; 'low' elective
      restorative rectal resection; and preparation for colonic replacement of
      oesophagus.

PMID- 1994887
TI  - Closure of persistent post-proctectomy perineal sinus using a rectus muscle flap.
AB  - A persistent perineal sinus following proctocolectomy or proctectomy is a not
      infrequent complication associated with considerable morbidity. Two cases are
      presented where the perineal sinus was closed using a rectus abdominis flap. This
      method of closure allows safe, complete excision of the sinus and insertion of a
      muscle flap which completely fills the defect, enabling complete, primary healing
      of the perineum.

PMID- 1994888
TI  - Ischaemic colitis as a complication of left-sided large bowel obstruction: a case
      report.
AB  - Although obstructed left-sided colorectal cancer has traditionally been treated
      by a series of staged operations, there has been recent interest in the one-stage
      immediate resection technique. The case of a 72 year old woman who required 4
      operations for obstructed left-sided colorectal cancer is presented.

PMID- 1994889
TI  - Crohn's disease and anal carcinoma: an association? A case report and review of
      the literature.
AB  - We believe this is the first Australian reported case of anal carcinoma
      complicating Crohn's disease. The opportunity has been taken to present a
      detailed case report and review the increasing overseas literature about this
      problem.

PMID- 1994890
TI  - Direct inguinal hernias in the newborn.
AB  - Direct inguinal hernias occur in newborn babies, both term and premature. Five
      cases are reported to illustrate three types of direct hernia. The first is a
      direct weakness without associated significant indirect hernial sac; the second,
      a sliding direct hernia. The third might be called a 'secondary' direct weakness
      resulting from a primarily indirect hernia which assumes such large size and
      develops such a wide neck at the internal ring that the posterior wall of the
      inguinal canal is stretched and weakened. This is most likely to occur in very
      low birthweight babies, who develop giant inguinoscrotal hernias. Full
      exploration and repair of the posterior wall of the inguinal canal should be
      performed in such babies with huge indirect hernial sacs and in all babies where
      the size of the processus vaginalis identified at the internal ring is not
      consistent with the hernial swelling identified clinically. Repair should be
      performed in conventional manner with non-absorbable sutures reinforcing the
      transversalis fascia. Overlying Bassini repair with or without Tanner's slide can
      be performed. The repair should be carried out before the baby leaves a high
      dependency area.

PMID- 1994891
TI  - Bladder endometriosis: three case reports and a review.
AB  - Endometriotic involvement of the bladder, although uncommon, is being reported in
      the literature with increasing frequency. Three cases are presented which will
      serve to highlight the main features of the disease and its management.

PMID- 1994892
TI  - Monocyte chemotactic proteins from human tumor cells.
AB  - The production of the monocyte chemoattractant MCP-1 suggests a common mechanism
      for the recruitment of monocytes/macrophages and provides an explanation for
      monocyte/macrophage infiltration frequently observed in solid tumors. The
      regulated production of MCP-1 by non-transformed cells further substantiates the
      suggestion that MCP-1 is an important inflammatory mediator and is involved in
      the recruitment of monocytes in a number of pathologic or physiologic conditions.

PMID- 1994893
TI  - Antitumour imidazotetrazines--XXIV. Growth suppression by DNA from cells treated
      with imidazotetrazinones.
AB  - Transfection of a murine colon adenocarcinoma cell line (MAC13) with DNA
      extracted from GM892 or Raji cells previously treated with either the methyl-
      (temozolomide) or ethyl-(CCRG82019) imidazotetrazinones caused a dose-related
      suppression of cell growth. The effect was proportional to the concentration of
      DNA transfected and the time of incubation of the donor cell lines with the
      drugs. It was not shown with X-irradiated DNA suggesting that the effect did not
      arise from non-specific damage to the DNA. Transfection of MAC13 cells with DNA
      extracted from GM892 cells was more effective in inhibiting growth than DNA from
      Raji cells, and temozolomide treated cellular DNA was a more potent growth
      inhibitor than that from CCRG 82019 treated cells. For both agents the growth
      inhibitory effect was most marked with DNA extracted 6 hr after drug addition and
      thereafter the effect decreased up to 24 hr after drug addition. This suggests
      that the growth inhibitory effect is due to a repairable lesion, and that the
      terminal mechanism of action of these agents involves targets after DNA.

PMID- 1994894
TI  - Interactions of bambuterol with human serum cholinesterase of the genotypes EuEu
      (normal), EaEa (atypical) and EuEa.
AB  - Bambuterol, a carbamate ester prodrug of the bronchodilator terbutaline, was
      tested as inhibitor and substrate of human serum cholinesterases of the genotypes
      EuEu (the normal enzyme), EaEa (the atypical enzyme) and EuEa. The IC50 for the
      normal enzyme was 11 +/- 2.2 nM (mean, SD, N = 10) and for the atypical enzyme
      140 +/- 6 nM (N = 13), indicating a much higher affinity of bambuterol to the
      normal enzyme. The heterozygotes showed a mixed behaviour; the major activity was
      inhibited like the normal enzyme (IC50 = 9.3 +/- 1.9 nM, N = 9), while a residual
      activity (10-15%) was inhibited by bambuterol like the atypical enzyme. At a
      bambuterol concentration of 100 nM each of the three cholinesterase genotypes
      responded uniquely to bambuterol; the normal enzyme was inhibited to 2.2 +/-
      0.9%, the atypical enzyme to 58 +/- 4.6%, and the heterozygote to 10 +/- 1.2% of
      the basal activity. Bambuterol may therefore be added to the list of inhibitors
      useful in the genotyping of cholinesterases. Bambuterol was much less efficiently
      hydrolysed in serum containing the atypical cholinesterase than in serum
      containing the normal enzyme. The results of the hydrolysis experiments once
      again illustrate the difference in affinity of bambuterol to the genetic forms of
      cholinesterase, and also strengthen the evidence that cholinesterase is the major
      serum enzyme catalysing the hydrolysis of bambuterol.

PMID- 1994895
TI  - Toward an understanding of the schistosomicidal effect of 4-methyl-5-(2
      pyrazinyl)-1,2-dithiole-3-thione (oltipraz).
AB  - In order to gain an interpretation of the schistosomicidal effect of 4-methyl 5
      (2-pyrazinyl)-1,2-dithiole-3-thione (oltipraz), chemical, electrochemical and
      enzymatic hypotheses are discussed from a pharmacological standpoint. The
      enzymatic hypothesis is in good agreement with experimental results which
      ascertain that oltipraz behaves as a prodrug.

PMID- 1994896
TI  - The role of metallothionein in the reduction of cisplatin-induced nephrotoxicity
      by Bi3(+)-pretreatment in the rat in vivo and in vitro. Are antioxidant
      properties of metallothionein more relevant than platinum binding?
AB  - Nephrotoxicity induced by cisplatin (CDDP) was reported to be reduced by Bi3(+)
      pretreatment, which selectively induces renal metallothionein (MT). In the
      present study renal MT had increased to 250% of control in rats that received
      bismuth subnitrate (50 mumol/kg/day, orally) for 8 days. In vitro experiments
      demonstrated that the reduction of CDDP-induced toxicity is a renal effect: in
      proximal tubular cells (PTC) isolated from Bi3(+)-treated rats the toxicity of
      CDDP, and also of HgCl2, CdCl2 and p-aminophenol, was reduced as compared to PTC
      from untreated rats. In contrast to the reduction in CDDP, Hg2+ and Cd2+
      toxicity, the reduction in p-aminophenol toxicity cannot be explained by the
      metal-binding properties of MT. MT was reported to act as a free radical
      scavenger, which may explain our observation since p-aminophenol toxicity is
      thought to be a consequence of the generation of oxygen radicals. In vivo
      experiments showed that the overall renal Pt-content as well as the Pt bound to
      renal MT is lower in Bi3(+)-pretreated rats than in untreated rats, 24 hr after
      administration of CDDP (12 mg/kg), suggesting that the reduction in
      nephrotoxicity is not due to increased binding of Pt2+ to renal MT. Renal
      superoxide dismutase (SOD) activity was increased in rats that had only received
      CDDP. Such a rise in SOD may result from peroxidative damage caused by exposure
      to CDDP. The fact that SOD was not elevated in rats that received Bi3+ prior to
      CDDP suggests that (i) peroxidation contributes to CDDP-induced nephrotoxicity
      and (ii) the anti-oxidant properties of MT are responsible for the reduction of
      this toxicity.

PMID- 1994897
TI  - Binding of vinca alkaloid analogues to human serum albumin and to alpha 1-acid
      glycoprotein.
AB  - The binding of a series of vinca alkaloid analogues having eburnane or indolo[2,3
      a]quinolizidine skeletons was studied with human serum albumin (HSA) by affinity
      chromatography and with alpha 1-acid glycoprotein by means of competition
      experiments. On HSA the binding occurs at the benzodiazepine-indole binding site
      via hydrophobic interaction and shows slight stereoselectivity preferring the
      trans isomers. The binding to alpha 1-AGP proved to be highly stereoselective in
      favour of the trans isomers having 3(S),16(R)eburnane or 1(R),12b(S)indolo[2,3
      a]quinolizidine absolute configurations.

PMID- 1994898
TI  - Monoclonal antibody-directed characterization of cytochrome P450 isozymes
      responsible for toluene metabolism in rat liver.
AB  - Monoclonal antibodies (MAbs) were used to study the contribution of cytochromes
      P450IA1/IA2, P450IIB1/IIB2, P450IIC11/IIC6 and P450IIE1 to toluene side-chain
      (benzyl alcohol, BA, formation) and ring (o- and p-cresol formation) oxidation in
      liver microsomes from fed, one-day fasted, and phenobarbital (PB)-, 3
      methylcholanthrene (MC)- and ethanol-treated rats. All rats were fed synthetic
      liquid diets. MAb 1-7-1 against P450IA1/IA2 inhibited markedly o-cresol formation
      and slightly p-cresol formation but not BA formation only in microsomes from MC
      treated rats. MAbs 2-66-3, 4-7-1 and 4-29-5 against P450IIB1/IIB2 strongly
      inhibited BA, o-cresol and p-cresol formation only in PB-induced microsomes. MAb
      1-68-11 against P450IIC11/IIC6 inhibited BA formation at high toluene
      concentration in the following order: fed greater than fasted greater than
      ethanol = MC greater than PB, and ethanol greater than or equal to fed = fasted
      greater than MC greater than PB on the basis of the percentage and net amount
      inhibition, respectively. MAb 1-91-3 against P450IIE1 inhibited BA formation at
      low toluene concentration, but not at high concentration, in the following order:
      ethanol greater than fasted = fed greater than MC, and ethanol greater than
      fasted greater than fed greater than MC on the basis of percentage and net
      inhibition, respectively. MAbs 1-68-11 and 1-91-3 also inhibited p-cresol
      formation at high and low toluene concentrations, respectively. These results
      indicate that (i) both P450IIE1 and P450IIC11/IIC6 are constitutive isozymes
      mainly responsible for the formation of BA and p-cresol from toluene as low- and
      high-Km isozymes, respectively; (ii) P450IIE1, but not P450IIC11/IIC6, is induced
      by one-day fasting and ethanol treatment; (iii) both P450IIE1 and P450IIC11/IIC6
      are decreased by PB and MC treatments; (iv) P450IIE1 is inhibited by high
      concentration of toluene; (v) P450IIB1/IIB2 can contribute to the formation of
      BA, o- and p-cresol from toluene, while P450IAI/IA2 preferentially contributes to
      the formation of o-cresol.

PMID- 1994899
TI  - Different inhibition and induction profiles of hepatic drug metabolism in rats
      and dogs by two structurally related pyridyl diazinone cardiotonic agents.
AB  - ICI 153,110 and ICI 170,777, two pyridyl diazinone cardiotonic agents, produced a
      different profile of effects on hepatic microsomal mixed function oxidase enzymes
      following multiple oral dosing to rats and dogs; these differences may be related
      to the molecular dimensions of the two molecules. ICI 153,110 significantly
      increased levels of total P450, ethoxycoumarin O-deethylase and ethoxyresorufin O
      deethylase in rat microsomes, indicating an induction profile (P448) similar to
      that of beta-naphthoflavone. This was supported by gel electrophoresis (SDS-PAGE)
      of microsomal proteins; a similar type of induction was observed in dog
      microsomes. In contrast, ICI 170,777 produced no changes indicating enzyme
      induction in either rat or dog. Instead, ICI 170,777 appeared to inhibit
      specifically the activity of aldrin epoxidase in the rat. Inhibitory activity was
      also indicated in the rat by prolongation of pentobarbitone sleeping time
      following single oral doses of either ICI 153,110 or ICI 170,777. The time-course
      of this effect appeared to correlate more closely with the profile of circulating
      metabolites, although both parent compounds were found to produce type II
      spectral changes on interaction with control rat microsomes. The molecular
      dimensions (area/depth2) of the compounds supported the finding that only ICI
      153,110 should interact with or induce P448 isozymes.

PMID- 1994900
TI  - The effect of diabetes on the in vivo acetylation capacity of the spontaneously
      diabetic, insulin-dependent BB/Edinburgh Wistar rat.
AB  - In contrast to previous studies using chemically-induced diabetic rats, the in
      vivo acetylation of sulphamethazine is increased in spontaneously diabetic,
      insulin-dependent BB/Edinburgh (BB/E) Wistar rats compared to non-diabetic
      control animals from the same colony. In both diabetic and non-diabetic rats,
      male animals had a significantly higher acetylation capacity than female animals.
      The percentage recovery of the administered dose was significantly higher in
      urine samples from female rats.

PMID- 1994901
TI  - Hepatic clearance and biliary secretory rate maximum of taurocholate in the
      recirculating and single pass isolated perfused rat liver. Effects of the
      cholestatic agent, estradiol-17 beta-(beta-D-glucuronide).
AB  - The ability of the cholestatic steroid glucuronide, estradiol-17 beta-(beta-D
      glucuronide) (E(2)17G), to inhibit the hepatic clearance (ClH) and biliary
      secretory rate maximum (SRm) of taurocholate was investigated in the
      recirculating and single pass isolated perfused male rat liver. In the
      recirculating perfused liver, E(2)17G (0, 2, 4, or 6 mumol) was added as a bolus
      dose to the reservoir at zero time while taurocholate was infused into the portal
      vein in increasing amounts (15, 30, 45, or 60 mumol/mL; 1 mL/hr for 15 min each).
      E(2)17G (4 mumol) caused a significant (P less than 0.05) inhibition of bile flow
      and bile acid secretion at 10-15 min during infusion of 15 mumol/hr taurocholate
      but did not inhibit the SRm which occurred at 42 min, indicating that E(2)17G had
      not caused an irreversible inhibition of taurocholate transport. E(2)17G (6
      mumol) caused a profound and irreversible inhibition of bile flow attributable to
      retention of E(2)17G in the liver. The noncholestatic estradiol-3-(beta-D
      glucuronide) (E(2)3G; 6 mumol) had no significant effect on bile flow or the SRm.
      In the single pass perfused liver (10 mL/min flow rate), E(2)17G (0, 1, 2, 5, or
      10 nmol/mL) or E(2)3G (2 nmol/mL) was added to the perfusate resulting in a
      stable infusion to the liver. [3H]Taurocholate was infused into the portal vein
      in increasing amounts to give inflow concentrations (Cin) of 25, 50, 75 or 100
      nmol/mL. In the absence of E(2)17G, taurocholate ClH decreased from 0.92 to 0.70
      mL/min/g liver with increasing taurocholate concentrations. Neither E(2)17G nor
      E(2)3G altered the ClH of 25 nmol/mL taurocholate. E(2)17G (10 nmol/mL) inhibited
      bile flow and bile acid secretion first at 20-25 min, followed by inhibition of
      ClH of 75 and 100 nmol/mL taurocholate (35-60 min). In contrast, E(2)3G
      stimulated bile acid secretion and increased the SRm by 80%. Thus, at doses that
      did not block its own elimination, E(2)17G did not cause an irreversible
      inhibition of taurocholate transport into bile. E(2)17G did not directly inhibit
      the uptake of taurocholate into the liver but first inhibited the biliary
      excretion of taurocholate, resulting in its intrahepatic accumulation and
      decreased clearance from the perfusate.

PMID- 1994902
TI  - Effects of sodium 2-[5-(4-chlorophenyl)pentyl]-oxirane-2-carboxylate (POCA) on
      fatty acid oxidation in fibroblasts from patients with peroxisomal diseases.
AB  - The effects of sodium 2-[5-(4-chlorophenyl)pentyl]oxirane-2-carboxylate (POCA), a
      potent inhibitor of carnitine palmitoyltransferase I, on fatty acid oxidation
      were investigated using fibroblasts from control subjects and from patients with
      peroxisomal disorders. [1-14C]Palmitate oxidation was inhibited by 8% of the
      control value when 15 microM POCA was added to the medium. The inhibition by POCA
      was significantly (P less than 0.05) stronger in fibroblasts from patients with
      Zellweger syndrome or with neonatal adrenoleukodystrophy, in which peroxisomes
      and peroxisomal beta-oxidation enzymes were absent. However, the inhibition in
      fibroblasts from patients with X-linked adrenoleukodystrophy, in which a specific
      defect of peroxisomal lignoceroyl-CoA synthetase was speculated, was similar to
      that in the controls. [1-14C]Lignocerate oxidation was not influenced by the
      addition of POCA, in samples from the controls and from the patients. These
      results indicate that peroxisomes account for a small but demonstrable proportion
      of palmitate oxidation, and add new evidence to the concept that lignocerate is
      oxidized exclusively in the peroxisomes. Our findings also support the hypotheses
      that the activity of palmitoyl-CoA synthetase and the enzymes of beta-oxidation
      cycle in peroxisomes are normal in patients with X-linked adrenoleukodystrophy
      and that a specific defect of lignoceroyl-CoA synthetase is responsible for the
      accumulation of very long chain fatty acids in these patients.

PMID- 1994903
TI  - Serum pseudocholinesterase activity in rabbits fed simvastatin.

PMID- 1994904
TI  - Comparison between cobalt and pyrazole in the increased expression of coumarin 7
      hydroxylase in mouse liver.
AB  - The data in this report show that administration of both cobalt and pyrazole
      results in an elevation in the amount of hepatic mRNA encoding for microsomal
      P45015 alpha/P450Coh, an increase in the amount of P450Coh protein, and an
      activation of COH and to a lesser extent testosterone 15 alpha-hydroxylase in two
      inbred strains of mice. Considerable quantitative differences between the two
      compounds and the two mouse strains in the response suggest that the effects of
      cobalt and pyrazole are mediated, at least partly, through different mechanisms.
      It is of interest that human hepatic COH resembles very closely that in the mouse
      liver.

PMID- 1994906
TI  - Characterization of liver microsomal cytochrome P450 from rats treated with
      muscone (3-methylcyclopentadecanone).

PMID- 1994905
TI  - Structure-activity relationships for various N-alkylcarbamyl esters of choline
      with selective nicotinic cholinergic properties.

PMID- 1994907
TI  - Determination of the in vivo antigen-antibody affinity constant from the
      redistribution of desipramine in rats following administration of a desipramine
      specific monoclonal antibody.
AB  - Quantitative expressions have been derived to determine the affinity constant for
      the in vivo interaction of an antigen with its elicited monoclonal antibody by
      analysing the redistribution of antigen following antibody administration. Using
      this method, the intrinsic binding constant for the interaction of subtoxic doses
      of DMI in rats with anti-TCA was found to be about two orders of magnitude less
      than the value obtained in vitro. The disparity is probably due to the presence
      of endogenous ligands for the antibody.

PMID- 1994908
TI  - Selective stimulation of carboxylesterases metabolizing charged steroid esters by
      hydrocortisone.
AB  - We observed a remarkable augmentation in the rate of hydrolytic breakdown of HCHS
      following exposure to corticosteroid therapy. This underscores the need for a
      careful reappraisal of its dosage in long term therapy. In such an event the
      uncharged ester may be the preferred drug of choice.

PMID- 1994909
TI  - Treatment of rheumatoid arthritis with an anti-CD4 monoclonal antibody.
AB  - The effect of treatment with a monoclonal antibody against the CD4 antigen
      present on T helper cells was studied in 10 patients with severe intractable
      rheumatoid arthritis. In an open trial, monoclonal antibody 16H5 was infused at a
      dosage of 0.3 mg/kg of body weight on 7 consecutive days. Studies of the kinetics
      demonstrated a drastic depletion of CD4+ cells, to as low as 25
      cells/microliters, 1 hour after the first infusion. The subsequent recovery of
      the CD4+ cell numbers 24 hours after infusion did not reach initial levels, and
      after the full 7-day treatment cycle there was a significant reduction of the
      number of CD4+ cells (mean +/- SD 51 +/- 28%; P less than 0.02). There was a
      reduced or even inverse CD4:CD8 ratio, which generally persisted 3-4 weeks.
      Lymphocyte transformation assays demonstrated significantly reduced reactivity in
      5 of the 9 patients who completed the 7-day course, whereas 4 individuals
      exhibited an unexpected elevation in the T cell response to mitogens and common
      antigens. Parallel laboratory studies showed a significant decrease in the
      erythrocyte sedimentation rate (P less than 0.05), rheumatoid factor titer (P
      less than 0.04), and total immunoglobulin values (P less than 0.01), as well as a
      reduction in C-reactive protein levels, in 7 of the 9 patients. Clinically, there
      was a significant reduction in the Ritchie articular index (P less than 0.05) and
      in the number of swollen joints (P less than 0.04). Adverse effects were
      urticaria in 2 patients, which led to withdrawal of therapy in 1 of them, and
      chills with fever, suggestive of a lymphokine release syndrome, in another 2
      patients. Only low levels of human anti-mouse immunoglobulin antibodies developed
      (not exceeding 1.7 mg/liter). It was therefore possible to repeat the treatment
      cycle, achieving still better efficacy, in 4 of the patients (reductions in the
      Ritchie index and the number of swollen joints P less than 0.02). Our findings
      indicate that treatment with monoclonal antibodies against the CD4 antigen leads
      to immunomodulation which results in clinical benefits, at least during initial
      observation periods (up to 6 months postinfusion). However, it remains to be
      determined whether long-term remission can be induced with this therapeutic
      approach. The use of immunosuppressive therapies or repeated antibody treatments
      will have to be considered.

PMID- 1994910
TI  - Persistence of monosodium urate crystals and low-grade inflammation in the
      synovial fluid of patients with untreated gout.
AB  - Synovial fluid (SF) from 74 asymptomatic knees of patients with gout was
      analyzed. These patients had never been treated with serum uric acid-lowering
      agents. SF samples were analyzed for the presence of crystals and for cell
      counts, using undiluted SF directly in a Niebauer cell counting chamber. Thirty
      seven of the aspirated knees had previously been inflamed, and monosodium urate
      (MSU) crystals were seen in SF aspirates from 36 of them (97%). Of the 37 knees
      that had never been inflamed, only 8 contained MSU crystals (P less than
      0.00001). After reaching the joint, MSU crystals will persist in the SF as long
      as the serum uric acid level has not been lowered by appropriate treatment. In
      this situation, analysis of SF is an excellent diagnostic test for the
      intercritical gout. The mean cell count in the 44 SF samples that contained MSU
      crystals was 449/mm3 (95% confidence interval 310-589); the mean cell count in
      the 30 SF without MSU crystals was 64/mm3 (95% confidence interval 34-95) (P less
      than 0.00002). The SF samples that contained MSU crystals also had a higher
      percentage of polymorphonuclear leukocytes than those without MSU crystals (P
      less than 0.002). These data suggest that there is a low-grade inflammation
      present in the knees of patients with MSU crystals, the consequences of which
      should be investigated.

PMID- 1994911
TI  - Local infectious complications following large joint replacement in rheumatoid
      arthritis patients treated with methotrexate versus those not treated with
      methotrexate.
AB  - We performed a 10-year retrospective analysis of the frequency of local
      postoperative infectious complications in methotrexate (MTX)-treated rheumatoid
      arthritis patients who underwent total joint arthroplasty. Sixty patients, who
      had a total of 92 joint arthroplasties, were receiving MTX. A comparison group of
      61 patients with a combined total of 110 total joint arthroplasties were not
      receiving MTX. The 2 groups were compared for the occurrence of local
      postoperative infectious complications and poor wound healing. Eight patients in
      the MTX group experienced a total of 8 complications (8.7% of procedures). In
      comparison, 5 patients in the non-MTX group experienced a total of 6
      complications (5.5% of procedures), a difference that was not statistically
      significant (chi 2 = 0.816, P = 0.366). Statistical analysis of many other
      variables revealed none that could be identified as risk factors for
      postoperative complications. These results suggest that treatment in the
      perioperative period with weekly low-dose pulse MTX does not increase the risk of
      local postoperative infectious complications or poor wound healing in rheumatoid
      arthritis patients who undergo total joint arthroplasty.

PMID- 1994912
TI  - Synovial membrane histology and immunopathology in rheumatoid arthritis and
      osteoarthritis. In vivo effects of antirheumatic drugs.
AB  - We examined the histologic and immunopathologic features of the synovial membrane
      of 18 patients with rheumatoid arthritis (RA) and 12 patients with osteoarthritis
      (OA) who had undergone total knee arthroplasty. Patients were classified into 5
      groups according to therapeutic regimen and disease: RA treated with nonsteroidal
      antiinflammatory drugs (NSAIDs), RA treated with NSAIDs and prednisone, RA
      treated with NSAIDs and methotrexate (MTX), OA treated with analgesics, and OA
      treated with NSAIDs. There were no significant between-group differences in the
      percentages or the distribution pattern of the infiltrating T cell subsets (CD4,
      CD8), HLA-DR, or interleukin-2 receptor-bearing cells. However, inflammatory
      indices, which included the thickness of the lining cell layer and the density of
      the mononuclear cell infiltrate, were significantly higher in the RA patients
      treated with prednisone and those treated with MTX (P less than 0.05). Similarly,
      fibrosis was markedly reduced in these 2 groups. The RA patients treated with
      NSAIDs alone and the 2 groups of patients with OA demonstrated similar profiles.
      These data suggest that prednisone and MTX may inhibit the development of
      fibrosis without altering the subsets of the inflammatory cell population. This
      observation raises the possibility that the action of these 2 drugs may be partly
      mediated by the suppression of inflammatory mediators that are responsible for
      fibroblast activation.

PMID- 1994913
TI  - In vivo effects of nonsteroidal antiinflammatory drugs on rat skin and synovial
      mast cell-induced vasopermeability.
AB  - Using our animal model of synovial mast cell-mediated arthritis in rats, we
      tested the effects of 3 nonsteroidal antiinflammatory drugs (NSAIDs) (aspirin,
      indomethacin, and ketoprofen) and an H1 and an H2 histamine receptor antagonist
      (diphenhydramine and cimetidine, respectively) on synovial and dermal mast cell
      induced vasopermeability. Drug effects were assessed by quantifying the leakage
      of radiolabeled albumin into tissues following specific antigen-initiated
      activation of passively sensitized dermal and synovial mast cells. The 3 NSAIDs
      tested had different effects on synovial and dermal mast cell-induced
      vasopermeability. Aspirin and indomethacin significantly increased dermal and
      synovial plasma exudation (P less than or equal to 0.008). Ketoprofen decreased
      dermal (P = 0.015), but had no effect on synovial, vascular exudation. Complete
      histamine H1 and H2 receptor blockade with diphenhydramine and cimetidine,
      respectively, substantially decreased (P less than or equal to 0.0008), but did
      not completely inhibit, dermal and synovial mast cell-induced vasopermeability.
      However, the addition of indomethacin to the combined antihistamine regimen
      resulted in an increase in the leakage of the radiolabel into skin and synovium
      (back to control levels), despite the complete blockade of H1 and H2 receptors.
      Results of experiments with antihistamines and indomethacin suggest that
      mediators other than histamine are involved in synovial mast cell-induced
      inflammation. Furthermore, the differential response to ketoprofen indicates that
      the specific antigen-stimulated mediator release profiles of dermal and synovial
      mast cells are different. Our finding of enhanced synovial vascular leakage in
      animals treated with some NSAIDs, and no such effect by other NSAIDs, perhaps
      explains in part the diverse effects of these agents in humans with arthritis.

PMID- 1994914
TI  - Spontaneous degenerative polyarthritis in male New Zealand black/KN mice.
AB  - Histopathologic studies and radiographic analysis revealed that male New Zealand
      black/KN (NZB/KN) mice develop degenerative polyarthritis in the joints of the
      forepaw and hindpaw beginning at age 2 months. Deposits of autoantibodies were
      observed on proliferating collagen fibers, nuclei of chondrocytes, and epidermal
      cells. Increases in the frequency of positivity for rheumatoid factor and anti
      type II collagen antibodies and in the level of serum oxidation activity were
      noted in these mice. The joint disease in male NZB/KN mice was transferable to
      female NZB/KN mice and male BALB/c mice by intraperitoneal injection of spleen
      cells from the male NZB/KN mice. This animal model of arthritis will be extremely
      useful for analyzing not only the pathogenesis of rheumatoid arthritis, but also
      new strategies for its treatment, since NZB/KN mice, unlike MRL/lpr mice, do not
      develop severe lupus nephritis or lymph-adenopathy, and therefore have a longer
      survival period.

PMID- 1994915
TI  - Down-regulation of adoptive adjuvant-induced arthritis by suppressor factor(s).
AB  - We recently described a method for inducing immunologic tolerance to
      trinitrochlorobenzene (TNCB), a hapten that generates suppressor cells capable of
      down-regulating the efferent phase of TNP-specific contact hypersensitivity in
      rats. Peritoneal exudate cells (PEC) of such tolerized rats, upon being triggered
      by specific hapten, suppressed contact hypersensitivity to another hapten
      elicited at the same time. This implied that cells that mediate delayed-type
      hypersensitivity of any specificity might be down-regulated, provided that the
      suppressor cells are activated with specific antigen and that the unrelated
      delayed-type hypersensitivity is elicited in parallel. To rigorously test this
      possibility, we examined the ability of TNP-specific suppressor lymphoid cell
      factors to affect cells that mediate adoptively transferable adjuvant-induced
      arthritis (AIA) in rats. To induce arthritis, spleen cells from Freund's complete
      adjuvant-injected rats were stimulated with concanavalin A and administered to
      naive recipients. Prior to adoptive transfer, the cells were exposed for brief
      intervals to supernatants of lymphoid cells from control and hapten-tolerized
      rats. Supernatants of PEC and lymph node cells from hapten-tolerized rats were
      found to markedly reduce the effectiveness of cells that mediate AIA. The hapten
      tolerized cells required reexposure to hapten prior to preparation of the
      supernatants. Supernatants of spleen cells from hapten-tolerized rats that had
      been hapten-painted as well as hapten-triggered and supernatants of lymph node
      cells and of PEC from only hapten-painted or hapten-triggered rats were
      ineffective in altering the AIA. Thus, factors from suppressor cells induced
      toward hapten-coupled self-antigens have been found to adversely affect the
      function of lymphoid cells that mediate a totally unrelated inflammatory
      response, namely, AIA. The clinical implications of these findings are discussed.

PMID- 1994916
TI  - Clinical correlations with serum C1q levels in patients with rheumatoid
      arthritis.
AB  - Previous studies have suggested that serum C1q levels measured during the first 5
      years of rheumatoid arthritis (RA) may be predictive of the extent of subsequent
      joint damage. To further evaluate the clinical significance of this marker in RA,
      levels of C1q were measured by radial immunodiffusion in serum samples from 107
      well-characterized patients with RA. Mean levels of C1q were higher in patients
      with a disease duration less than or equal to 5 years (173 micrograms/ml) than in
      patients with a disease duration greater than 5 years (148 micrograms/ml) (P =
      0.032). Serum C1q levels were correlated with total joint counts and activities
      of daily living scores, but no correlation was observed with erythrocyte
      sedimentation rates or with radiographic scores. The results suggest that C1q may
      be a useful early marker of disease activity in patients with RA.

PMID- 1994917
TI  - HLA-D region antigens in patients with rheumatoid arthritis.
AB  - We studied the distribution of HLA-D region antigens in 2 groups of rheumatoid
      arthritis (RA) patients: those with mild, nonprogressive disease, and those with
      severe disease. The results demonstrate that DR4 was significantly increased in
      both RA patient populations. The frequencies of DR1 and DR4-associated DQw7
      alleles, however, were different in these 2 groups of patients. DR1 was
      significantly increased only in patients with mild RA, and DR4-associated DQw7
      was significantly increased only in patients with severe disease. The results of
      the present study, together with previous data from our laboratory and from other
      investigators on the incidence of HLA-D region antigens in RA, suggest that both
      DR and DQ (A and B) genes may be important in conferring susceptibility to RA; DR
      in the mild forms of the disease, and DQ in severe RA.

PMID- 1994918
TI  - The effect of nifedipine on myocardial perfusion and metabolism in systemic
      sclerosis. A positron emission tomographic study.
AB  - We assessed the effect of nifedipine on myocardial perfusion and metabolism in 9
      patients with systemic sclerosis, using positron emission tomography with a
      perfusion tracer (potassium-38) and a metabolic tracer (18F-fluorodeoxyglucose
      [18FDG]). Nifedipine, 20 mg 3 times daily for 1 week, induced a significant
      increase in 38K myocardial uptake, a significant decrease in 18FDG myocardial
      uptake, and a significant increase in the myocardial 38K: 18FDG ratio. These
      results indicate that the increase in myocardial perfusion is associated with
      modifications in myocardial energy metabolism, which probably result from a
      beneficial anti-ischemic effect of nifedipine in patients with systemic
      sclerosis.

PMID- 1994919
TI  - Temporal arteritis with normal erythrocyte sedimentation rates presenting as
      occipital neuralgia.
AB  - A retrospective review of 46 patients with biopsy-proven giant cell (temporal)
      arteritis revealed 8 (17%) whose initial presentation was occipital pain. The
      most likely etiology of occipital pain in these patients was occipital artery
      inflammation. A Westergren erythrocyte sedimentation rate less than 40 mm/hour
      was noted at presentation in 6 of these 8 patients. Giant cell arteritis should
      be considered in the differential diagnosis of elderly patients who present with
      occipital pain and demonstrate a normal erythrocyte sedimentation rate.

PMID- 1994920
TI  - Wegener's granulomatosis presenting as temporal arteritis.
AB  - A granulomatous giant cell vasculitis of the temporal artery was observed in a
      biopsy specimen from a patient with corresponding clinical symptoms. Within
      weeks, the new onset of pulmonary infiltrates and renal failure prompted biopsy
      of the patient's kidney. A necrotizing glomerulonephritis, compatible with a
      diagnosis of Wegener's granulomatosis, was present. Vasculitis of the temporal
      artery may be a feature of Wegener's granulomatosis.

PMID- 1994921
TI  - Association of the complement allele C4AQ0 with primary Sjogren's syndrome in
      Japanese patients.
AB  - We studied allotypes of the fourth component of complement (C4) and factor B in
      76 patients with Sjogren's syndrome (SS) and in 63 normal subjects. C4A-null
      (C4AQ0) was found in 10 of 28 patients who had primary SS, compared with 1 of 63
      control subjects (P less than 0.005). In contrast, no significant difference in
      the frequency of any C4 allotype was observed between patients with secondary SS
      and control subjects. An association of HLA-DRw53 with primary SS in Japanese
      patients has been reported. Since there is no linkage disequilibrium between
      DRw53 and C4AQ0, it is possible that at least 2 genes in the major
      histocompatibility complex may determine susceptibility to the development of
      primary SS in the Japanese population.

PMID- 1994922
TI  - Fatal pulmonary venoocclusive disease secondary to a generalized venulopathy: a
      new syndrome presenting with facial swelling and pericardial tamponade.
AB  - We describe a patient who developed fatal pulmonary artery hypertension secondary
      to diffuse venulitis. This otherwise healthy young woman first presented with
      generalized venulopathy, with chemosis, facial swelling, pleural effusions, and
      pericardial tamponade. The symptoms partially responded to steroid therapy, but
      over a 2-year course, a rapidly progressive and fatal venoocclusive disease
      developed. No other primary condition was diagnosed, and at autopsy, the patient
      had striking venulitis throughout, including the pulmonary bed. We believe that
      this is a unique case of pulmonary hypertension resulting from a generalized
      venulopathy.

PMID- 1994923
TI  - Research priorities for arthritis professional education.

PMID- 1994924
TI  - Paget's pseudosarcoma.

PMID- 1994925
TI  - Elevated plasma levels of endothelin-1 in systemic sclerosis.

PMID- 1994926
TI  - Treatment of systemic sclerosis with antithymocyte globulin.

PMID- 1994928
TI  - Comment on the article by Robinson et al.

PMID- 1994927
TI  - Regression of an expanded subpopulation of large granular lymphocytes in a
      patient with rheumatoid arthritis.

PMID- 1994929
TI  - Rheumatoid arthritis: a twentieth century disease in Africa?

PMID- 1994930
TI  - Autoantibodies to DNA, lamins, and pore complex proteins produce distinct
      peripheral fluorescent antinuclear antibody patterns on the HEp-2 substrate.

PMID- 1994931
TI  - Reactive arthritis from Blastocystis hominis.

PMID- 1994932
TI  - Felty's syndrome: response to cyclosporin A with disappearance of neutrophil
      autoantibodies.

PMID- 1994933
TI  - Factors associated with the safety of EMS helicopters.
AB  - The accident rate for emergency medical service (EMS) helicopters is thought to
      be approximately twice the rate for other commercial (Part 135) helicopters. This
      observation has led to numerous news reports and to the publication of
      conclusions of a National Transportation Safety Board investigation. The data for
      these reports come from investigations of EMS helicopter accidents and incidents.
      The authors surveyed all listed civilian EMS helicopter programs to examine both
      helicopter ambulance mishaps and the number of safely completed missions.
      Epidemiological methods were then used to compare the safety records of different
      groups of EMS helicopters. The single most important factor identified was the
      number of flights made by the program during the study period: busy programs had
      an eightfold lower accident rate (P less than .0005) and a three-fold lower total
      mishap (accidents + incidents) rate (P less than .0005) than less active
      programs. Programs with the ability to fly under instrument flight rules (IFR) at
      the pilots discretion had no mishaps (P = .044) during the study period.
      Multivariate analysis shows this IFR capability to be marginally significant as
      an independent factor (P = .099).

PMID- 1994934
TI  - Evaluation of drug therapy for treatment of hypertensive urgencies in the
      emergency department.
AB  - Oral nifedipine (N) and clonidine (C) are often used in the treatment of
      hypertensive urgencies; however, until recently, there were no comparative
      studies using the same patient population. The authors reviewed the records of
      hypertensive patients treated in the emergency department between October 1, 1987
      and September 30, 1988. Selected patients had a diastolic blood pressure (DBP) of
      greater than 115 mm Hg without evidence of acute end organ damage. Patients were
      stratified into three treatment groups: N, C, and group 3 (G3). G3 received a
      variety of drug therapies but not exclusively N or C. Systolic blood pressure
      (SBP), DBP, mean arterial pressure (MAP), percent decrease in MAP (%MAP), time to
      lower blood pressure, admissions, and discharges were evaluated. Efficacy and
      safety were defined as reaching a DBP less than 110 mm Hg but %MAP of no greater
      than either 25% or 40%, respectively. Thirty-five N, 32 C, and 27 G3 patients
      were identified with no statistical difference between groups in race, gender,
      pretreatment SBP, DBP, or MAP. N, C, and G3 significantly reduced SBP, DBP, and
      MAP (P less than .01). Comparing N, C, and G3, no differences were observed in
      %MAP, admissions, discharges, efficacy, or safety. Time required to decrease
      blood pressure differed between all three groups (44 +/- 32 N v 77 +/- 57 C v 152
      +/- 94 min G3) (p less than .05). These results indicate that N, C, and a variety
      of drug therapies are equally effective and safe in the treatment of hypertensive
      urgencies.

PMID- 1994935
TI  - Risk monitoring of randomized trials in emergency medicine: experience of the
      Brain Resuscitation Clinical Trial II.
AB  - Risk monitoring for the Brain Resuscitation Clinical Trial II, a multicenter,
      placebo-controlled trial to evaluate the efficacy of the calcium-entry blocker
      lidoflazine in the amelioration of brain damage in comatose cardiac-arrest
      survivors, posed unexpected challenges. Concern arose when monitoring of adverse
      reactions showed an excess of dangerous cardiac arrhythmias, including rearrest,
      in the lidoflazine group. To ascertain the cause of this problem and determine
      whether it was ethical for the trial to continue, an in-depth review of data was
      conducted, outside experts were consulted, and additional data were collected.
      These efforts suggested possible causes for the problem. Existing drug
      administration protocols for blood pressure control were reinforced, resulting in
      lower subsequent arrhythmia rates. Thus, through an efficient monitoring system,
      an important problem was uncovered and resolved, allowing the trial to be
      completed without major changes.

PMID- 1994936
TI  - Early diagnosis and survival of ruptured abdominal aortic aneurysms.
AB  - The hospital records of patients treated with ruptured abdominal aortic aneurysm
      in a recent 5-year period were reviewed to collect data on factors which may be
      associated with mortality. Overall mortality was 62%. Patients with
      intraperitoneal rupture had a higher mortality (97%) than patients with
      retroperitoneal rupture (25%). Patients at increased risk were older than 80
      years, presented with syncope, experienced a short duration of symptoms prior to
      emergency department (ED) arrival, had initial systolic blood pressure less than
      90 mm Hg, and/or initial hemoglobin level less than eight on arrival at the ED
      and delay in beginning surgery. Multivariate analysis demonstrated preoperative
      blood pressure, preoperative hemoglobin, presence of syncope, and the amount of
      blood transfused were largely reflections of the type of rupture and had only
      slight independent relationship to mortality. The authors concluded that treating
      emergency physicians and surgeons have little control over the most important
      risk factors for mortality after aneurysm rupture, but may improve the prognosis
      by expediting diagnosis in the ED and surgical therapy.

PMID- 1994937
TI  - Treatment and career attitudes of prehospital care providers associated with
      potential exposure to HIV/AIDS.
AB  - Career and treatment attitudes related to potential human immunodeficiency virus
      and acquired immunodeficiency syndrome (HIV/AIDS) exposure are reported based on
      a survey of 1,228 Maryland career and volunteer prehospital care providers
      trained to provide basic (BLS) and advanced (ALS) life support. Sixty-five
      percent stated potential exposure to HIV/AIDS was a major occupational stressor.
      Ninety-two percent stated they would treat HIV/AIDS patients if protected. Given
      a choice, 38% would avoid providing treatment to HIV/AIDS patients. Eighteen
      percent considered resigning from emergency medical services (EMS) work. An
      attitudinal scale (AIDSTRESS) was developed to evaluate overall treatment and
      career reactions. Respondents with significantly higher (more negative reactions)
      AIDSTRESS scores were: BLS providers, men, paid providers, personnel with more
      than 3 years of field experience, those working in urban areas, personnel with no
      formal education beyond high school, and those who stated that their HIV/AIDS
      training was inadequate. Implications of the findings for quality of care, career
      decision making, and inservice education are discussed.

PMID- 1994939
TI  - Diagnostic capabilities of magnetic resonance imaging and computed tomography in
      acute cervical spinal column injury.
AB  - The present study was conducted to evaluate the imaging capabilities of magnetic
      resonance imaging (MRI) in evaluating acute cervical spinal column injury and
      compare these results to that of computed tomographic (CT) imaging. Forty-nine
      patients undergoing MRI at a Level I and regional spinal cord trauma center to
      evaluate cervical spinal column injury were studied. Seventy-one injuries were
      identified by MRI. These injuries were classified as osseous
      (fracture/dislocation) (n = 21), disc herniation (n = 29), and spinal cord injury
      (edema/contusion/transection) (n = 21). Diagnostic imaging results in 33 of the
      49 patients undergoing both MRI and CT were compared. CT demonstrated 22
      fracture/dislocations compared to 10 on MRI. MRI demonstrated 19 disc protrusions
      compared to 7 on CT. Additionally, MR imaged 13 cord injuries as compared to 0 by
      CT. MR imaging proved superior in demonstrating spinal cord pathology and
      intervertebral disc herniation. CT was superior to MRI in demonstrating osseous
      injury. CT and MRI may be useful together in determining presence and extent of
      spinal column injury.

PMID- 1994938
TI  - Patient flow in the emergency department: the chest pain patient.
AB  - Prompt treatment of the chest pain patient in the emergency department (ED) is
      crucial. To ensure prompt treatment, identification of factors that delay flow of
      these patients through the department is essential. To identify factors that
      delay patient flow through the ED, the authors conducted a prospective study of
      all chest pain patients, using a time-flow analysis. Eighty-eight (36%) of 245
      patients required critical unit admissions and had an average department stay of
      3 1/2 hours. Flow differences were seen between critical and noncritical care
      patients. Three primary sources of delay were identified: critical unit bed
      availability, the registration process, and the role of the unit admitting
      resident. Additional findings confirmed the efficacy and role of the triage nurse
      in patient flow. Nursing and medical education and staffing needs were addressed.
      The use of the community's emergency medical services was examined by analyzing
      the disposition of patients arriving at the ED by ambulance.

PMID- 1994940
TI  - Oral labetalol in hypertensive urgencies.
AB  - The response to incremental doses of oral labetalol in 16 patients with
      hypertensive urgencies is presented. After inadequate blood pressure control with
      20 mg of intravenous furosemide, each patient received a 300 mg oral dose of
      labetalol. Subsequent oral doses of labetalol, 100 mg, were administered at 2
      hour intervals, if the diastolic blood pressure remained greater than 100 mm Hg.
      The maximum dose of labetalol per patient was 500 mg. Five patients required only
      the initial 300 mg dose of labetalol. Two patients required further therapy for
      satisfactory blood pressure control. Mean arterial pressure fell from 156 +/- 12
      mm Hg to 123 +/- 14 mm Hg.

PMID- 1994941
TI  - Cerebral circulation and metabolism in patients with septic encephalopathy.
AB  - Cerebral circulation and metabolism in septic encephalopathy have not been well
      documented. The authors measured cerebral blood flow (CBF) and metabolic rate for
      oxygen (CMRO2) in six patients with septic encephalopathy associated with
      multiple organ failure (three to five organs). They found that CBF and CMRO2 were
      significantly lower than awake control values of 46 +/- 2 to 28 +/- 3 mL/100g/min
      (mean +/- SEM) and 3.1 +/- 0.2 to 1.2 +/- 0.2 mL/100g/min, respectively. Cerebral
      vascular resistance (CVR) and cerebral circulatory index (CCI:CBF/CMRO2) were
      significantly higher than the control values of 2.0 +/- 0.1 to 3.0 +/- 0.4 mm
      Hg/mL/100g/min and 15.1 +/- 0.8 to 24.2 +/- 3.3, respectively. At the time of
      cerebral circulatory and metabolic measurements, their consciousness varied
      between 4 and 10 as evaluated by the Glasgow coma scale. The electroencephalogram
      showed diffuse slow wave activity and the latency of the auditory brain stem
      evoked response was prolonged in four of six patients. Computed brain tomography
      showed either no abnormality or mild atrophy. It is concluded that CBF and CMRO2
      are disproportionally decreased during septic encephalopathy in association with
      dysfunction of the CNS and decreased electrical activity.

PMID- 1994942
TI  - Container residue after the administration of aqueous activated charcoal
      products.
AB  - Commercial aqueous activated charcoal (AC) products may sit in emergency
      departments, pharmacies, and homes for prolonged periods resulting in the
      inability to resuspend the AC for patient administration. The potential risk to
      the patient from not receiving an adequate amount of AC, especially when AC may
      be the sole means of gastric decontamination, is obvious. To simulate this
      potential problem, samples of five different aqueous AC products (ActaChar,
      Actidose, InstaChar, LiquiChar, and SuperChar) were placed into storage for
      periods of 3 and 12 months. At the end of each study period, samples were
      agitated and the effluent and container residue were collected, oven-dried, and
      weighed. With the exception of Actidose, all products retained substantial
      amounts of AC in the container at both time intervals. These data stress the
      negative impact of dormant storage on the resuspendability of aqueous activated
      charcoal products. Furthermore, they suggest the importance of thorough container
      agitation and rinsing to insure that the patient receives sufficient AC. This is
      especially important when AC is the sole means of decontamination.

PMID- 1994943
TI  - All-terrain vehicle mortality in Wisconsin: a case study in injury control.
AB  - All-terrain vehicles (ATVs) have resulted in over 1,400 deaths and 400,000
      injuries in the United States since their introduction in the 1970s. Analysis of
      deaths due to ATVs have been limited to a few states. Death certificates for ATVs
      were abstracted for the years 1983 through 1989 in Wisconsin. Fifty-two deaths
      were analyzed; 44 (85%) were male, and 26 (50%) were under age 18. Head injuries
      accounted for 33 (63%) of the deaths. Thirty-one of the deaths (60%) were
      "immediate", occurring in "seconds", "minutes", or "immediately". Following the
      model developed by Haddon, there are several promising injury-control strategies:
      limiting the use of ATVs to those sixteen or older, increasing visibility of
      vehicles through means such as flags, increasing helmet usage, and improving
      emergency medical systems services. Many of these strategies are best promoted
      through statewide legislative policy changes. This injury study model of ATV
      deaths suggest that a more balanced approach towards injury reduction should have
      an equal emphasis on improving injury prevention and acute care.

PMID- 1994944
TI  - Evaluation of minor head trauma in children younger than two years.
AB  - The recent medical literature emphasizes the limitations of skull films in the
      evaluation of minor head trauma. However, the emergency medicine literature
      places little emphasis on the particular risks in children younger than 2 years
      old with blunt head injury. These children have immature bone and unfused sutures
      that may increase risk of cranial injury and delayed complications. A case is
      presented to illustrate this point. Unlike severe head trauma, where evaluation
      is directed toward computed tomography, the literature continues to be
      controversial regarding the indications for skull radiographs and computed
      tomography in minor head trauma. The authors recommend a low threshold for
      radiographic imaging in blunt heat injuries in children younger than 2 years.

PMID- 1994945
TI  - Bilateral vocal cord hematomas associated with shoulder harness use.
AB  - A case of bilateral vocal cord hematomas caused by a shoulder harness injury is
      presented. The patient was restrained by a three-point belt system and was
      involved in a front-end collision. She presented with mild facial and chest
      injuries and a contusion of the neck. One hour after injury she began to complain
      of hoarseness without airway compromise. Fiberoptic laryngoscopy showed bilateral
      true vocal cord hematomas. The patient had an uneventful hospital course and a
      full recovery. The importance of the mechanism of injury and associated injuries
      is discussed.

PMID- 1994946
TI  - Saltpeter ingestion.
AB  - A 37-year-old man presented to the emergency department after an attempt to self
      treat his priapism with saltpeter (K+NO3). Initially he had a potassium of 7.6
      with electrocardiographic changes and a markedly elevated CO2. The potassium and
      carbon dioxide normalized in less than 24 hours with standard treatment for
      hyperkalemia. Hyperkalemia is expected with large oral potassium ingestion; and
      the elevated CO2 was spurious, caused by the misreading of serum nitrates by the
      Ektachrom 700 system. Ingestion of K+NO3 should be added to the differential of
      hyperkalemia with a markedly elevated CO2.

PMID- 1994947
TI  - Accuracy of common drug screen tests.
AB  - Forty consecutive urine specimens, obtained from patients seen in the emergency
      center, positive for either cocaine and/or marijuana, were analyzed using five
      methods of analysis. A new latex agglutination inhibition assay, Abuscreen
      OnTrak, (Roche Diagnostic Systems, Nutley, NJ), was compared with four other drug
      abuse assays: mass spectrometry, (Hewlett-Packard Co, Richardson, TX); an
      automated homogeneous enzyme immunoassay technique, ETS System, (Syva Co, Palo
      Alto, CA); a manual enzyme multiplied immunoassay technique; EMIT-st, (Syva); and
      a fluorescence polarization immunoassay, TDx, (Abbott Laboratories, Chicago, IL).
      For statistical purposes, mass spectrometry was the reference point for the
      presence or absence of a specific substance. All instrument sensitivities, with
      the exception of mass spectrometry, were set with the same "cut off" point of 100
      micrograms/L for marijuana and 300 micrograms/L for cocaine and its metabolites.
      Efficiency in the detection of cocaine and its metabolites was 95% by all
      methods. Efficiency for the detection of marijuana and its metabolites ranged
      from 70% (Roche's OnTrak) to 90% (Syva's ETS). Simple to use, assays of minimal
      cost are presently available for rapid, accurate drug of abuse screening.

PMID- 1994948
TI  - Self-administered intraurethral chlorpromazine: an unusual cause of priapism.
AB  - Priapism is a prolonged, painful penile erection unaccompanied by sexual desire
      and not alleviated by ejaculation. The etiologies of priapism are numerous and
      diverse. Priapism can be a serious adverse effect of psychotropic medications.
      The case of a 36-year-old man who demonstrated priapism, 48 hours after inserting
      a crushed chlorpromazine tablet into the urethral meatus of his penis, is
      reported. Priapism induced by this route of drug administration has not been
      previously described. The pathophysiology and treatment of priapism are reviewed.

PMID- 1994949
TI  - Tension pneumothorax associated with hyperbaric oxygen therapy.
AB  - The authors present three patients who developed a tension pneumothorax while
      receiving emergent hyperbaric oxygen therapy for acute carbon monoxide poisoning.
      Each patient was intubated and received closed chest compressions for cardiac
      arrest prior to hyperbaric oxygenation. Despite the apparent absence of
      pneumothorax prior to hyperbaric therapy, tension pneumothorax was detected soon
      after decompression. These cases illustrate the need for vigilance in detecting
      and addressing pneumothorax prior to hyperbaric decompression in obtunded
      patients. Serial physical examinations, arterial blood gas determinations,
      properly positioned chest radiographs, and a high index of suspicion for
      pneumothorax in the setting of emergent hyperbaric therapy are recommended.

PMID- 1994950
TI  - Anterior shoulder dislocation: a review of reduction techniques.

PMID- 1994951
TI  - Basic trauma life support: what is it?

PMID- 1994952
TI  - Critical care medicine: an annotated bibliography of the recent literature.

PMID- 1994953
TI  - Transtracheal jet ventilation and airway obstruction.

PMID- 1994954
TI  - Acute nitrate poisoning: a report of 80 cases.

PMID- 1994955
TI  - Oxycodone-induced pulmonary edema.

PMID- 1994956
TI  - Loxosceles envenomation.

PMID- 1994957
TI  - Needles on wheels.

PMID- 1994958
TI  - Theophylline levels in COPD exacerbations.

PMID- 1994959
TI  - Carbon monoxide screening in the ED.

PMID- 1994960
TI  - Pacing the injured heart.

PMID- 1994961
TI  - Accelerated wound healing of pressure ulcers by pulsed high peak power
      electromagnetic energy (Diapulse).
AB  - The purpose of this study was to evaluate the effect of pulsed high-frequency,
      high peak power electromagnetic energy (Diapulse) in the healing of pressure
      ulcers. Patients with Stage II ulcers unhealed within three to 12 weeks and those
      with Stage III ulcers unhealed within eight to 168 weeks by conventional methods
      were included in the study. When Diapulse was added to conventional therapy
      during the nine-month study, all 22 patients healed as evidenced by photographs
      and measurements of the ulcers. Stage II ulcers healed in one to six weeks (mean
      2.33) and all Stage III ulcers healed in one to 22 weeks (mean 8.85). The
      increased healing time can provide significant cost savings and improved patient
      care.

PMID- 1994962
TI  - Practice guidelines for management of pressure ulcers.
AB  - Pressure ulcers are a significant and increasing source of human suffering. The
      precise number of people who have pressure ulcers is unknown. However,
      conservative estimates indicate that well over a million persons in hospitals and
      nursing homes suffer from pressure ulcers. One large study found that one in four
      Americans who died in 1987 had a dermal ulcer. The prevalence of pressure ulcers
      is almost certain to grow due to increasing numbers of fragile elderly and
      survivors of serious trauma.

PMID- 1994963
TI  - Quality care and staging of ulcers.

PMID- 1994964
TI  - Words, words, words.

PMID- 1994965
TI  - New approaches in the rehabilitation of the traumatic high level quadriplegic.
AB  - The use of noninvasive alternatives to tracheostomy for ventilatory support have
      been described in the patient management of various neuromuscular disorders. The
      use of these techniques for patients with traumatic high level quadriplegia,
      however, is hampered by the resort to tracheostomy in the acute hospital setting.
      Twenty traumatic high level quadriplegic patients on intermittent positive
      pressure ventilation (IPPV) via tracheostomy with little or no ability for
      unassisted breathing were converted to noninvasive ventilatory support methods
      and had their tracheostomy sites closed. Four additional patients were ventilated
      by noninvasive methods without tracheostomy. These methods included the use of
      body ventilators and the noninvasive intermittent positive airway pressure
      alternatives of IPPV via the mouth, nose, or custom acrylic strapless oral-nasal
      interface (SONI). Overnight end-tidal pCO2 studies and monitoring of
      oxyhemoglobin saturation (SaO2) were used to adjust ventilator volumes and to
      document effective ventilation during sleep. No significant complications have
      resulted from the use of these methods over a period of 45 patient-years.
      Elimination of the tracheostomy permitted significant free time by
      glossopharyngeal breathing for four patients, two of whom had no measurable vital
      capacity. We conclude that noninvasive ventilatory support alternatives can be
      effective and deserve further study in this patient population.

PMID- 1994966
TI  - Proportional myoelectric hand control: an evaluation.
AB  - The authors review the principle of proportional myoelectric control, in which
      the motor voltage of a prosthetic hand varies in direct proportion to the EMG
      signal, giving the amputee control over speed and force of grip. This type of
      myoelectric control is contrasted with digital myoelectric control, in which the
      system is fully on or off, giving the amputee no control over speed of hand
      opening and closing, and the grip force is increased only by increasing the time
      of the sustained EMG signal. A survey was conducted of 33 patients wearing the
      proportional myoelectric hand. Patients rated quickness of opening and closing;
      control over speed and force; effort required to open and close; and comfort,
      convenience, and cosmesis of the hand; as well as giving it an overall rating in
      comparison with their previous terminal device. The ratings were made on a 5
      level scale, so that they could be quantified. Patient responses were grouped
      according to previous experience with a terminal device type: group A: digital
      myoelectric hand; group B: body-powered terminal device; group C: no terminal
      device. Differences in group means were compared using Student's t test. Previous
      digital hand wearers gave significantly higher ratings to the proportionally
      controlled hand overall, especially for its quickness, control of speed and
      force, and the effort required to open and close the hand. Former body-powered
      terminal device wearers rated the proportionally controlled hand significantly
      better on control over speed and force and on cosmesis.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1994967
TI  - Effects of a topically applied counterirritant (Eucalyptamint) on cutaneous blood
      flow and on skin and muscle temperatures. A placebo-controlled study.
AB  - This study was designed to investigate the effects of a new product of
      counterirritant, Eucalyptamint, on the cutaneous circulation and on skin and
      muscle temperatures. Ten normal subjects (six males and four females, with an
      average age of 34 +/- 6 yr) were involved in this study. Eucalyptamint was
      applied to the anterior forearm skin of one side, and placebo was applied to the
      contralateral forearm. The subjective feelings, cutaneous blood flow, and skin
      temperature were measured before and periodically (5-min intervals) after the
      application of the compound. Muscle temperature was measured before and 30 min
      after the application of the Eucalyptamint. There was no significant effect on
      the subjective sensation. However, there were statistically significant (P less
      than 0.05) increases in cutaneous blood flow (up to 4 times base-line) and skin
      temperatures (up to 0.8 degrees C higher than base-line) after the application of
      Eucalyptamint with the effects lasting up to 45 min after the application. The
      muscle temperature was also increased (0.4 degrees C) significantly (P less than
      0.05) 30 min after application of the Eucalyptamint. There were no significant
      changes in the placebo application. The results of this study suggested that the
      new product of counterirritant, Eucalyptamint, produced significant physiologic
      responses that may be beneficial for pain relief and/or useful to athletes as a
      passive form of warm-up.

PMID- 1994968
TI  - High resolution real-time ultrasound for the diagnosis of venous thrombosis in
      the rehabilitation setting.
AB  - Accurate, noninvasive testing for deep venous thrombosis (DVT) by conventional
      methods is often not possible in the rehabilitation patient. Lower extremity
      amputation, a cast or bandage, or skin problems present obstacles to standard
      diagnostic methods. This report describes the use of duplex ultrasound (US)
      scanning for noninvasive diagnosis of DVT in a seventy-year-old man with a below
      knee amputation, on whom Doppler and plethysmography examinations could not be
      performed. As experience is gained with this technique, the use of venography for
      diagnosis of DVT becomes more difficult to rationalize.

PMID- 1994969
TI  - Intramuscular recording of H-reflexes from muscles of the posterior compartment
      of the lower leg.
AB  - This study was designed to elucidate the role of different muscles of the
      posterior compartment of the lower leg in the generation of the surface-recorded
      H-reflex. H-reflexes were evoked through percutaneous stimulation of the
      posterior tibial nerve and recorded concurrently, using monopolar electrodes from
      the soleus (SOL), medial and lateral gastrocnemii (MG and LG), tibialis posterior
      (TP), flexor digitorum longus (FDL), and flexor hallucis longus (FHL). There were
      significant (P less than 0.01) differences in the amplitudes, latencies, and
      modified H:M ratios of the responses recorded from the different muscles. The SOL
      modified H:M ratios were consistently the highest (x = 1.02), while the H:M
      ratios for MG (x = 0.34) and LG (x = 0.37) were consistently the lowest.
      Latencies of H-reflexes obtained from proximal recording sites (x = 29.2 ms) were
      significantly shorter than those from the most distal site (x = 31.5 ms). These
      results establish the contribution made by various deep and superficial muscles
      to the conventionally recorded H-reflex and help explain the differences in H
      reflex amplitudes and latencies when recordings are made from different sites.

PMID- 1994970
TI  - Research in physical medicine and rehabilitation. XII. Measurement tools with
      application to brain injury.
AB  - There are basic principles and techniques of measurement that are relevant across
      biomedical disciplines. The purpose of this article is to explain some of the
      most important of these for medical rehabilitation, to illustrate how to use them
      to choose assessment instruments and to describe the nature of measurement in
      medical rehabilitation by examples in brain injury rehabilitation. Reliability is
      basic to any scientific measure. Validity, the ultimate criterion, is closely
      associated with the purpose of the measure. Content validity, criterion validity
      and construct validity are explained. Sensitivity to rehabilitative interventions
      and significance in patients' real lives (ecological validity) are emphasized.
      Measures of functional outcomes (disability) may show improvement after
      rehabilitation even when impairment measures do not. An extensive but selected
      list of measures of coma, global status, disabilities, communicative and
      cognitive impairments, and handicaps is presented, and their main uses are
      illustrated. Examples illustrate how to choose measures to study comprehensive
      program-level outcomes, to study learning-based interventions and to develop a
      general purpose database. Although there are many measures of activities of daily
      living and mobility, little published evidence of reliability and validity could
      be found even for some well-known scales. Ecologically valid and sensitive
      outcome measures are especially needed. Studies of the clinical utility of
      measures were also scarce. Many of these gaps can be spanned by clinical
      researchers with limited resources. Physical medicine and rehabilitation will
      benefit from formal studies of the reliabilities and validities of both its old
      and its new measurement instruments and by increased sophistication in choice of
      measures.

PMID- 1994971
TI  - Recovery time of independent function post-stroke.
AB  - Stroke patients undergoing physical rehabilitation were monitored daily to
      determine the length of time needed to recover independent function. Of the 93
      patients admitted, there were 45 who could not attain the sitting position
      independently, 75 who could not walk independently and 75 who could not negotiate
      the stairs independently. By discharge, 25 of 45 patients (55.6%) were able to
      attain sitting from supine independently, 35 of 75 patients (46.7%) achieved the
      ability to walk independently but only 25 of 75 patients (33.3%) learned to
      negotiate stairs independently. The time from admission to achievement of
      independent function and the time from onset of stroke to achievement of
      independent function was modeled in relation to explanatory variables: age, sex,
      side of lesion, comorbidity, the presence of depression and the extent of
      impairment in perception, cognition, auditory comprehension and verbal
      expression. Four variables were found to influence recovery time: age influenced
      the rate of recovery of walking and stair climbing; perceptual impairment
      influenced the rate of achieving independent sitting and stair climbing; and
      depression and comprehension influenced walking.

PMID- 1994972
TI  - Comparative analysis of health risk assessments for municipal waste combustors.
AB  - Quantitative health risk assessments have been performed for a number of proposed
      municipal waste combustor (MWC) facilities over the past several years. This
      article presents the results of a comparative analysis of a total of 21 risk
      assessments, focusing on seven of the most comprehensive methodologies. The
      analysis concentrates on stack emissions of noncriteria pollutants and is
      comparative rather than critical in nature. Overall, the risk assessment
      methodologies used were similar whereas the assumptions and input values used
      varied from study to study. Some of this variability results directly from
      differences in site-specific characteristics, but much of it is due to absence of
      data, lack of field validation, lack of specific guidelines from regulatory
      agencies, and reliance on professional judgment. The results indicate that
      carcinogenic risks are more significant than chronic non-carcinogenic risks. In
      most instances polychlorodibenzodioxins, polychlorodibenzofurans, and cadmium
      contribute more significantly to the total carcinogenic risk from MWC stack
      emissions than other contaminants. In addition, the contribution to total risk of
      all indirect routes of exposure (ingestion and dermal contact) exceeds that of
      the direct inhalation route for most studies reviewed.

PMID- 1994973
TI  - Fogwater chemistry in a wood-burning community, western Oregon.
AB  - Fogwater chemistry in Corvallis, Oregon, a wood-burning community (pop.
      approximately 43,000) was compared with the chemistry of fogwater collected in
      more remote and in more highly industrialized areas. The fogwater was not acidic
      (median pH = 5.7) and was usually dominated by SO4=, NO3-, and NH4+ whose
      concentrations were generally lower than in fogwater in other urban areas but
      higher than in remote areas. Concentrations of formic and acetic acids (medians =
      61 and 52 microN, respectively) were comparable to those in fogwater in Los
      Angeles, California and were typically much higher than concentrations in
      fogwater from more remote areas. Formate and acetate concentrations were often
      comparable to those of SO4= and NO3-. Formaldehyde concentrations (range = 0.4
      3.0 mg L-1) were comparable to those in fogwater in some urban areas of southern
      California, yet lower than concentrations in highly industrialized areas of
      southern California. Because concentrations of organic compounds in Corvallis
      fogwater were often comparable to those in larger urban areas, sources in
      addition to motor vehicles must be important in Corvallis. Additional sources may
      be natural and anthropogenic, the latter including residential wood burning and
      wood products industries.

PMID- 1994974
TI  - Thermal and catalytic incinerators for the control of VOCs.
AB  - The emission of Volatile Organic Compounds (VOCs) is attracting increasing
      concern both from the public and by government agencies. Among the many available
      control technologies for the treatment of VOC containing waste streams,
      incineration offers an ultimate disposal strategy rather than a means for
      collecting or concentrating the offending compounds. This paper describes the
      major, commercially available thermal and catalytic incinerator systems that are
      designed to treat dilute, VOC containing gas streams. Qualitative guidelines are
      presented whereby the technologies can be compared. In addition, an example waste
      stream is used to illustrate a simplified procedure for calculating the material
      and energy balances for each of the incinerators. The resulting parameters will
      be used in a companion paper to estimate the capital and operating costs
      associated with each design. In this manner, a first estimate can be obtained of
      the costs of cleaning a waste stream containing low levels of VOCs.

PMID- 1994975
TI  - Thermolability of mouse oocytes is due to the lack of expression and/or
      inducibility of Hsp70.
AB  - Eukaryotic and prokaryotic cells have been shown to respond to physical and
      chemical stress by the induction of proteins called heat shock proteins. Heat
      shock protein 70 (Hsp70), is the most ubiquitous of these proteins. Although heat
      shock proteins are generally thought to protect cells from physiologically
      stressful stimuli, it cannot be assumed that this is so, because several cases
      exist in which thermotolerance is acquired without the production of heat shock
      proteins, and in several other cases the hyperproduction of these heat shock
      proteins does not produce thermotolerance. In this study we show that
      unfertilized mouse oocytes are sensitive to elevated temperatures, and that the
      synthesis of Hsp70 cannot be induced in these oocytes. Furthermore, our data
      demonstrate that the expression of Hsp70 in mouse oocytes is sufficient for the
      acquisition of thermotolerance. Mouse oocytes were injected with mRNA for Hsp70,
      and the viability of these oocytes was determined after heating. The number of
      viable oocytes was significantly higher in the group injected with Hsp70 mRNA and
      then heated compared with oocytes injected with Hsp70 antisense mRNA and sham
      injected controls treated in an identical manner. No significant differences in
      the number of viable oocytes were found between the group that had been injected
      with Hsp70 mRNA, heated, and then allowed to recover for 3 hr and the group
      maintained at 37 degrees C throughout.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1994976
TI  - Nonisotopic in situ hybridization as a method for nondisjunction studies in human
      spermatozoa.
AB  - Human spermatozoa were studied with a nonradioactive in situ hybridization
      method. Using a chemically modified DNA probe and immunocytochemical reactions
      for visualization, it was possible to obtain hybridization signals in 31 of 32
      semen samples. Positive hybridization reactions, depending on cell accessibility,
      varied from 40% to over 90% for the different samples. Using a chromosome 1
      specific DNA probe, disomy for this chromosome was found in 0.67% of all
      accessible sperm cells.

PMID- 1994977
TI  - Dynamics of paternal chromatin changes in live one-cell mouse embryo after
      natural fertilization.
AB  - Using video-enhanced fluorescence microscopy, we describe in live mouse zygotes
      the paternal chromatin changes undergone after fertilization. We focus on the
      sperm recondensation process and the formation of the paternal pronucleus, in
      relationship with the progression of maternal chromatin. Chromatin is labeled
      with the vital fluorophore Hoechst 33342. Our conditions of dye concentration and
      irradiation allow a continuous following of the dynamics of changes without major
      perturbation. We combine these observations with ultrastructural analysis
      performed by electron microscopy of the same eggs fixed at chosen stages. We show
      that the highly recondensed state corresponds to the appearance of the nuclear
      envelope and therefore the beginning of the pronuclear stage.

PMID- 1994978
TI  - Immunoreactive inhibin in follicular fluid is related to meiotic stage of the
      oocyte during final maturation of the porcine follicle.
AB  - The concentration and content of inhibin was determined in individual porcine
      follicles from gilts ovariectomized at various times after the onset of estrus.
      In one experiment, gilts (n = 5) were ovariectomized at 0, 10, or 20 hr after the
      onset of estrus and the follicular fluids from all large follicles individually
      aspirated. In a second experiment, gilts (n = 6) were ovariectomized at 21, 24,
      27, 30, or 34 hr after the onset of estrus; follicular fluids were aspirated; and
      each oocyte was stained and evaluated for cytogenetic stage of meiotic
      maturation. Inhibin was determined in diluted follicular fluids with a
      radioimmunoassay based on a synthetic peptide replica of part of the alpha
      subunit of porcine inhibin. Inhibin values were expressed in terms of thousands
      of units (kU) of a World Health Organization inhibin standard (86/690).
      Concentration of inhibin did not vary among hours (overall mean 248 kU/ml). Total
      follicular content of inhibin also was not different among hours (overall mean 57
      kU/follicle). When follicles were classified on the basis of the maturation of
      the oocyte, significant differences were found. Concentration of inhibin in
      follicles with a germinal vesicle-stage oocyte was 138 kU/ml, whereas follicles
      with more mature oocytes had concentrations of between 204 and 254 kU/ml.
      Follicular content of inhibin showed a similar pattern with 34.9 kU/follicle at
      germinal vesicle stage, increasing to 42.5-56.1 kU/follicle at later stages.
      Quantities of inhibin were also negatively skewed and were positively correlated
      to follicular content of estradiol and dermatan sulfate.

PMID- 1994979
TI  - Subzonal microinjection of mouse spermatozoa: insufficient sperm motility might
      induce phagocytosis.
AB  - Acrosome-reacted CB6F1 mouse spermatozoa with slight flagellar motility were
      microinjected under the zona pellucida of CB6F1 mouse oocytes. Electron
      microscopy revealed the presence of swollen and decondensed sperm heads in the
      oocyte cytoplasm. Sixty-one percent of the microinjected oocytes reached a
      morphologically apparent two-cell stage, but chromosomal analysis demonstrated
      only haploid chromosomal complements in all cases. The exposure of microinjected
      oocytes to suspensions of spermatozoa of mice homozygous for a 2,4 reciprocal
      translocation resulted in normal fertilization and embryonic development with a
      maternally as well as a paternally derived haploid genome. Identical results were
      obtained with oocytes microinjected with medium and subjected to in vitro
      fertilization thereafter. Thus it can be suggested that the microinjected
      spermatozoa with insufficient flagellar motility are incorporated into the oocyte
      cytoplasm by phagocytosis. These spermatozoa do not induce a polyspermy block but
      induce the oocyte to parthenogenetic development.

PMID- 1994981
TI  - Identification of spectrin and calmodulin in rabbit spermiogenesis and
      spermatozoa.
AB  - Actin was localized in the four subacrosomal bulges (Camatini et al., Eur. J.
      Cell Biol. 45:276-281, 1987), which characterize the sperm head of rabbit
      spermatozoa (Phillips, J. Ultrastruct. Res. 38:591-604, 1972), and in the
      postacrosomal region (Welch and O'Rand, Dev. Biol. 109:411-417, 1985; Camatini et
      al., Eur. J. Cell Biol. 45:276-281, 1987). Specific antibodies and indirect
      immunogold labelling on testis Lowicryl K4M sections and spermatozoa cryosections
      were used to study the distribution of calmodulin and a spectrin-like protein.
      This protein was also present close to the shaping membranes of the head. The
      results presented suggest a membrane-cytoskeletal role of actin, spectrin, and
      calmodulin.

PMID- 1994980
TI  - The binding characteristics of cholinergic sites in rabbit spermatozoa.
AB  - Binding of neurotrophic ligands to rabbit spermatozoa was studied. Nicotinic
      cholinergic antagonists, [3H]alpha-bungarotoxin and [3H]dihydro-beta-erythroidine
      (DE), bound with high affinity to different sites in the tails of rabbit
      spermatozoa with the former binding to 10,207 sites/cell and the latter to 562
      sites/cell. alpha-Bungarotoxin and DE sites resemble nicotinic sites in brain in
      binding affinity and specificity. [3H]Quinuclidinyl benzilate (QNB), a muscarinic
      cholinergic antagonist, also bound with high affinity to a single class of sites
      located in the heads and tails of rabbit spermatozoa. The binding characteristics
      of the sperm muscarinic site are similar to muscarinic sites in both innervated
      and noninnervated cells. Rabbit spermatozoa incubated for 16-18 h in a medium
      which supported motility for an extended period possessed fewer binding sites
      than nonincubated spermatozoa for [3H] alpha-bungarotoxin and [3H]QNB and the KD
      for the latter ligand was also lower. Ligands specific for the kappa and delta
      opiate receptors showed no affinity for rabbit spermatozoa.

PMID- 1994982
TI  - Response of porcine oocytes to electrical and chemical activation during
      maturation in vitro.
AB  - These studies were conducted to examine activation of in vitro-matured porcine
      oocytes in response to an electrical stimulus or to an ionophore. Cumulus
      enclosed porcine oocytes were incubated in maturation medium supplemented with
      either FSH and LH (MM:Exp.1) or pregnant mare serum gonadotropin (PMSG; MM-P:
      experiments 2-4) at 39 degrees C in 5% CO2:95% air with high humidity. In
      experiment 1, groups of oocytes were stripped of cumulus and then shampulsed
      (control) or electrically pulsed with a Zimmerman Cell Fusion unit at 24, 31, 41,
      48, and 65 h of incubation. Control oocytes were exposed to the activation medium
      for 20 sec, whereas oocytes to be pulsed were subjected to a single activation
      pulse (120 V, 30 microseconds). Oocytes were cultured for an additional 24 h and
      then fixed and examined. For oocytes pulsed at 24, 31, 41, 48, and 65 h, the
      proportions which activated were 0, 0, 87, 88, and 83%, respectively. In
      experiment 2, oocytes were electrically or sham-pulsed with a BTX 200
      Embryomanipulation System at 24, 30, and 40 h of incubation and respective
      proportions of oocytes activating were 27%, 39%, and 72%. In experiment 3,
      oocytes were subjected to 0, 1, or 2 activation pulses after 41 h of incubation
      in MM-P. Double-pulsing halved the proportion of activated oocytes (P less than
      .0001). In experiment 4, oocytes were subjected to 0, 25, 50, or 100 microM
      ionophore at 48 h of incubation. Proportions of oocytes activated by ionophore
      were greater than for control (P less than .05), but activation was not increased
      by increasing dose of ionophore.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1994983
TI  - Further observations on the phagocytosis of Candida albicans by hamster and human
      oocytes.
AB  - Pathogenic yeast, Candida albicans, were incubated with hamster and human oocytes
      for up to 21 hours in order to determine the nature and time course of
      phagocytosis of these organisms. Aliquotes of the interacting cells were taken at
      various time intervals for electron microscopic examination. Some specimens had
      their zona pellucidae enzymatically removed prior to incubation with yeast, and
      these specimens showed the most extensive interaction and phagocytosis of
      Candida. The zona pullucida appears to be an effective barrier to yeast, at least
      over the time span studied. The observations are consistent with the hypothesis
      of an initial attachment of yeast via a surface component to oocyte microvilli
      followed by phagocytic uptake into an endosome. There is no compelling evidence
      of lysosomal degradation of the yeast over the time course of this study;
      however, the oocytes appear to undergo some degenerative changes at long
      incubation times.

PMID- 1994984
TI  - Development of the normal XY male and sex-reversed XXSxr pseudomale mouse
      epididymis.
AB  - XXSxr pseudomale mice (chromosomally XX animals "sex-reversed" by the Sxr factor)
      develop testes and produce sufficient androgens for masculinization as assessed
      at the macroscopic level. However, adult XXSxr pseudomales lack the epididymal
      initial segment (I.S.). In this study prenatal and postnatal epididymal
      development was examined histologically and biochemically, and it was found that
      XXSxr pseudomales are indistinguishable from normal XY males up to day 21 of
      postnatal life. By 25 days postnatally, before the onset of the pubertal androgen
      surge, the I.S. precursor is evident in normal animals but absent in XXSxr
      mutants. No major abnormalities were seen in other segments of the XXSxr
      epididymis. Our data suggest that androgen levels in testis and epididymis are
      not higher in normal XY males than in XXSxr pseudomale mice of the same age.
      Inadequate availability of androgens at the target site is unlikely to be the
      cause of the epididymal abnormality in XXSxr pseudomale mice.

PMID- 1994985
TI  - Transforming growth factor-alpha augments meiotic maturation of cumulus cell
      enclosed mouse oocytes.
AB  - Growth factors have been shown to play an important role in the regulation of
      ovarian function. In this study, we examined the effects of transforming growth
      factor-alpha (TGF-alpha) on the meiotic maturation of immature mouse oocytes in
      vitro. Cumulus cell-enclosed oocytes were exposed to TGF-alpha with or without
      the meiotic inhibitor hypoxanthine (HX), and oocyte maturation was assessed by
      germinal vesicle breakdown (GVBD). Likewise, mechanically denuded oocytes were
      examined for GVBD following exposure to HX and TGF-alpha. When cumulus cell
      enclosed oocytes were exposed to TGF-alpha (1 microgram/ml) in the presence of HX
      (4 mM), an increase in GVBD was observed first after 5 hours of culture. Maximal
      stimulation was reached at 24 hours when 70% of the oocytes underwent maturation
      in the presence of TGF-alpha and HX as compared to 33% with HX only.
      Concentrations of TGF-alpha as low as 0.1 ng/ml produced a similar stimulatory
      response after 24 hours of culture. Spontaneous maturation in the presence of TGF
      alpha, but without HX, was also enhanced. The stimulation of GVBD by TGF-alpha
      showed an increase over time both with and without HX. When denuded oocytes were
      exposed to TGF-alpha in the presence of HX, no effect was observed. Our results
      suggest that TGF-alpha is a potent stimulator of mouse oocyte maturation in vitro
      and that its effect is mediated by the surrounding cumulus cells.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1994986
TI  - The spermicidal effect of ethylene dibromide in bulls and rams.
AB  - The spermicidal effect of ethylene dibromide (EDB) in bulls and rams is reviewed.
      Following oral or parenteral administration EDB was found to cause, by its
      alkylating effect in the testes of treated bulls and rams, lysis of the chromatin
      of the elongating spermatids during the time of somatin histones replacement by
      the sperm protamines. However, while in the bulls the abnormal spermatozoa issued
      from the affected spermatids were also collected in the ejaculates, this was not
      the case with treated rams. In the latter animals the abnormal spermatids seem to
      be phagocytized in the epididymis before their arrival in the ejaculate. In
      addition, whereas the alkylating effect of EDB occurred also in the upper parts
      of the epididymis of the bulls, causing tail and acrosome defects to the
      spermatozoa, in the rams such an effect seems to occur all along the epididymal
      duct. These differences between bulls and rams in the sites of the genital tract
      where the drug takes effect, and in the mechanism of this effect, reveal probable
      differences in the physiology of the reproductive tract between these species.

PMID- 1994988
TI  - [A case of band heterotopia--a newly recognized migration disorder].

PMID- 1994987
TI  - [A study on computed tomography of three cases of Reye syndromes].

PMID- 1994989
TI  - [A case of central sleep apnea due to looping of the left vertebral artery].

PMID- 1994990
TI  - [Three dimensional brain surface MR imaging of the central nervous system
      anomalies in Fukuyama type congenital muscular dystrophy].

PMID- 1994991
TI  - [Evoked EMG in juvenile ocular myasthenia gravis].
AB  - We studied juvenile ocular myasthenia gravis (MG) with special reference to
      evoked EMG in orbicularis oculi muscle. The subjects consisted of 5 cases aged 1
      4 years and 3 cases over 10 years. Young children were examined during drug
      induced sleep. Stimulation was delivered to preauricular facial nerve, and M
      waves were recorded from ipsilateral orbicularis oculi muscle. Examinations were
      also carried out in thenar or hypothenar muscles by stimulating the median or
      ulnar nerves respectively. On Harvey-Masland test, 6 out of 8 cases showed waning
      of more than 10%. On M-wave recovery cycle, 3 out of 6 cases examined showed
      decrement during stimulation interval of 100 msec to 500 msec. In 2 of these, the
      peak of recovery cycle curve rose over 100% during stimulation interval of 30 to
      60 msec on a usual dose treatment of anti-cholinesterase, while on prednisolone
      treatment this peak did not increase over 100% and the pattern of recovery cycle
      changed to almost normal. On post-tetanic cycle study, only 1 out of 4 cases
      examined showed post-tetanic facilitation and exhaustion. The response of the
      belly-tendon in the hand showed no abnormality. Although there still remains
      technical difficulty in the examination of evoked EMG in orbicularis oculi
      muscle, this examination is very useful in diagnosis, evaluation and
      understanding of pathophysiology of MG.

PMID- 1994992
TI  - [Spectral analysis of heart rate variability in the dysfunction of the
      brainstem].
AB  - The heart rate variability, modulated by autonomic nervous system, has been
      reported to decrease in depression of the central nervous system, especially of
      the brainstem. To assess the brainstem dysfunction, we analyzed R-R interval
      values (the intervals between R waves of ECG) in 9 children (7 in comatose
      children and 2 in central apnea) by spectral analysis using an autoregressive
      model. The findings of spectral analysis were compared with those of auditory
      brainstem response (ABR). In comatose children with the brainstem dysfunction,
      the reduction of the total power was apparent before the appearance of ABR
      abnormality. In central apnea due to the dysfunction of respiratory center in
      brainstem, only the respiratory component decreased without the reduction of the
      total power or ABR abnormality. Spectral analysis of the heart rate variability
      is a useful means for assessment of the brainstem function.

PMID- 1994993
TI  - [Magnetic resonance imaging of skeletal muscle in patients with Duchenne muscular
      dystrophy--serial axial and sagittal section studies].
AB  - Magnetic resonance imaging of skeletal muscles in thirteen patients with Duchenne
      muscular dystrophy was performed to estimate pathological changes. Serial axial
      and sagittal sections of the right lower extremity were recorded. In the early
      stage, the T1 values of gastrocnemius and soleus muscles were slightly lower than
      the control values, and in the late stage, the values were much lower in all
      muscles examined. In sagittal sections, the gastrocnemius muscles in the early
      stage showed a high density area at the distal region adjacent to soleus muscle,
      and the soleus muscle showed a high density area adjacent to the gestrocnemius
      muscle. In serial axial sections, high density areas of the anterior and
      posterior tibialis muscles appeared first at their proximal and peripheral
      regions. It was concluded that the sequence of appearance of pathological changes
      was different not only among individual muscles but also among various regions of
      each muscle; the high density changes appeared first at myotendon junctions.

PMID- 1994994
TI  - [A longitudinal study of blood flow velocities in the anterior cerebral artery
      and the internal cerebral vein in the neonatal period].
AB  - Flow velocities in the anterior cerebral artery (ACA) and the internal cerebral
      vein (ICV) were studied by a Doppler ultrasound technique. A longitudinal study
      was undertaken on 59 newborn infants during the first month of life. The newborn
      infants were classified into 3 groups: 22 term infants, 21 preterm infants, and
      16 very low birth weight infants. A rapid linear increase of flow velocities was
      found in the ACA in the first month of life with higher velocities in neonates of
      higher birth weight. The index of resistance was not significantly different
      among the 3 groups. A linear increase of flow velocities was also found in the
      ICV in the same period. The velocities in the ICV were correlated with those in
      the ACA. These data suggest that the increasing velocities probably reflect the
      increasing cerebral blood flow during the first month of life.

PMID- 1994995
TI  - [Crossed cerebellar diaschisis demonstrated by SPECT in hemiplegic children].
AB  - Crossed cerebellar diaschisis (CCD) in twenty five children with hemiplegia were
      studied using single photon emission computed tomography (SPECT) with N-isopropyl
      p-I-123-iodoamphetamine. Seven of twenty-five patients had cerebral palsy, and
      the others were impaired by acquired brain injury between ten months and fourteen
      years of age. CCD was demonstrated in five patients (20%), who were impaired by
      acquired brain injury after seven years of age. CCD could never be detected in
      patients with cerebral palsy. Ipsilateral cerebellar diaschisis was also
      demonstrated in two patients with cerebral palsy and three with early acquired
      brain injury before three years of age. It is suggested that diaschisis presents
      itself as a different form in a contralateral and ipsilateral cerebellum before
      three years of age from a form which presents after seven years of age.

PMID- 1994996
TI  - [A mild variant case of maple syrup urine disease].
AB  - We reported a mild variant case of maple syrup urine disease. He was unable to
      walk alone at 2 years of age and developed seizures and intermittent ataxia at 5
      years of age. Activity of 1-14C-leucine decarboxylase in fibroblasts revealed 40%
      of normal activity in the boy and 90% in the mother. MRI showed hypo-myelination
      of white matter and mild atrophy of brain stem and cerebellum. Dietary treatment
      was not effective for ataxia and brain atrophy.

PMID- 1994997
TI  - [Multiple sclerosis with higher cerebral dysfunction: a case report].
AB  - Higher cerebral dysfunctions such as aphasia, apraxia and agnosia have seldom
      been reported in multiple sclerosis (MS). 12 year-old right-handed boy felt
      unsteadiness of the body and headache for several days. Two months later, he had
      the same episode and complained of visual disturbance, and weakness and sensory
      disturbance on the face and the extremities. Additionally, he showed amnestic
      aphasia, acalculia, ideomotor apraxia, finger agnosia and right-left
      disorientation. Cerebrospinal fluid examinations revealed increases IgG, myelin
      basic protein and neuron specific enolase (11%, 25 ng/ml and 28.8 ng/ml,
      respectively). X-ray CT scan and MRI-CT examinations revealed sclerotic lesions
      on the left parietal white matter and the right mid-brain. The diagnosis was made
      as MS. He was treated with m-PSL (methyl-prednisolone) pulse therapy for three
      weeks and consecutively treated with PSL for four weeks. He recovered gradually,
      but visual disturbance and facial palsy remained. After seven months MRI-CT
      showed a high signal intensity on the left parietal white matter in spite of the
      disappearance of the lesion on X-ray CT scan. We suggest that these higher
      cerebral dysfunctions may result from the lesion of the left parietal white
      matter which produces a disconnection between each cortical area.

PMID- 1994998
TI  - [A case of type I hyperprolinemia associated with photogenic epilepsy].
AB  - A 9-year-old girl with type I hyperprolinemia, who also had photogenic epilepsy,
      was reported. She showed epileptic discharges and the regression in speech and
      motor activities, since 7 years of age. Her plasma proline levels were 3 to 4
      times higher than control levels. In urine, iminoglycinuria appeared, when plasma
      proline value exceeded 0.80 mM. The proline oxidase activity of the liver tissues
      obtained by biopsy in the patient was about 23.5%, compared to that of controls.
      In spite of the restriction of proline and protein intake, she showed progressive
      speech and motor retardation.

PMID- 1994999
TI  - [Three cases of subacute panencephalitis showing asterexis-like movements].
AB  - We reported 3 cases with subacute sclerosing panencephalitis (SSPE) showing
      recurrent and involuntary motor phenomena. Their electroclinical correlates were
      analyzed using CCTV-EEG. Clinically, they slanted their trunks and/or heads, and
      dropped their upper limbs momentarily only when their antigravity muscles were
      suitably contracting (sitting, standing, or stretching out their arms).
      Electrographically, the motor phenomena corresponded with the occurrence of
      periodic synchronous discharges (PSD) (in one-to-one manner). EMG potentials
      associated with the muscle contraction subsided at the very moment. These motor
      phenomena observed in patients with SSPE were discussed in relation to asterexis.

PMID- 1995000
TI  - [Carnitine palmitoyltransferase deficiency in a patient with severe psychomotor
      retardation].
AB  - A 13-year-old girl who had severe brain damage due to unknown prenatal cause
      presented rhabdomyolysis triggered by a mild viral infection. Her muscle biopsy
      revealed mild variation in fiber size and type 2 fiber atrophy without excess
      lipid storage. Biochemical analysis of the biopsied material showed decreased
      carnitine palmitoyltransferase (CPT) activity (15% of the control). Serum and
      urinary carnitine levels were normal. Skeletal muscle CT scanning showed multiple
      low density spots. The patient was diagnosed as having CPT deficiency. She
      recovered from rhabdomyolysis without renal failure after a month with
      conservative therapy. CPT deficiency is usually found in young healthy persons.
      This is the first case report of CPT deficiency which presented severe
      psychomotor retardation since neonatal period.

PMID- 1995001
TI  - [Impaired cholesterol esterification in Niemann-Pick disease model mouse].

PMID- 1995002
TI  - Executive nursing leadership in the complex health care environment.

PMID- 1995003
TI  - Current issues for rural hospitals.

PMID- 1995004
TI  - Standards and quality assurance.

PMID- 1995005
TI  - Temporary cardiac pacing.
AB  - The use of temporary cardiac pacing in critical care and stepdown units has grown
      tremendously over the past 10 years. While the concept of artificial pacing is
      simple, improvements in generator technology and lead design, along with broader
      clinical applications, have made temporary cardiac pacing more complex.
      Consequently, the critical care nurse is required to maintain an advanced level
      of knowledge regarding modes and complications of temporary pacing, and
      assessment skills related to recognizing pacemaker hemodynamic effects and
      pacemaker problems.

PMID- 1995006
TI  - Transcutaneous cardiac pacing.
AB  - Pacemaker technology has experienced many advances. Today temporary pacing can be
      provided in several ways. This chapter examines one of these modalities,
      transcutaneous noninvasive pacing. In addition, this chapter reviews relevant
      historic milestones, describes transcutaneous pacing, state procedural aspects,
      and delineate important nursing aspects of care.

PMID- 1995007
TI  - Dual-chamber pacing.
AB  - Dual-chamber pacing has been available since the early 1980s, yet it is a topic
      with which critical care nurses consistently have difficulty. New advances in
      pacemaker technology have built on the principles inherent in dual-chamber
      pacing, making it imperative that practitioners have a basic understanding of
      dual-chamber pacemaker function. With dwindling clinical resources, the
      responsibility of the bedside nurse to evaluate appropriate pacemaker function
      and identify the patient's response to pacemaker therapy has increased.

PMID- 1995008
TI  - Pacing for tachydysrhythmias.
AB  - Advances in cardiac electrophysiology have clarified some of the mechanisms of
      tachydysrhythmias and have characterized tachycardias that are amenable to pace
      termination. Tachydysrhythmias most likely to be terminated by pacing techniques
      tend to be slow, re-entrant tachycardias. Although single extrastimulation can be
      effective, its yield is relatively low. Delivery of multiple extrastimuli or
      burst pacing are more effective than single extrastimulation at the expense of a
      higher risk of tachycardia acceleration or transformation of the rhythm to
      fibrillation. The use of pacing for the termination of tachydysrhythmias has
      primarily been limited to the acute care setting, although permanently
      implantable antitachycardia pacemakers are being used in increasing numbers.
      While these devices have been approved by the Food and Drug Administration (FDA)
      for the treatment of supraventricular tachydysrhythmias, their use to treat
      ventricular tachydysrhythmias has produced mixed results and remains
      investigational. In some cases of sustained ventricular tachycardia, automatic
      cardioverter/defibrillators have been implanted along with antitachycardia
      pacemakers to provide high-energy shock back-up in case of tachycardia
      acceleration by the pacemaker. Soon, devices will be available which will
      combine, in a single unit, antitachycardia pacing and high-energy
      cardioversion/defibrillation.

PMID- 1995009
TI  - Rate-responsive cardiac pacemakers.
AB  - Pacemaker technology continues to advance in the direction of restoring a normal
      hemodynamic response under varying physiologic conditions. Rate-responsive
      pacemakers meet this challenge by adjusting the pacing rate in response to a
      sensed physiologic variable other than sinus node activity. In an effort to
      design the ideal rate-responsive system, various physiologic cues have been
      tested. To translate shifts in the sensed physiologic indicator into an
      appropriate pacing rate, specialized sensor systems also have been developed and
      include mechanical, chemical, thermal, and electrical sensors. Although each
      sensor system offers advantages and disadvantages, continued research and
      clinical experience will determine the future of this exciting new form of
      cardiac pacing.

PMID- 1995010
TI  - Occurrence screening in critical care.
AB  - Occurrence screening is a system of quality assurance in which patient care is
      reviewed, both concurrently and retrospectively, against a set of general outcome
      screening criteria. It is a method for monitoring the quality of clinical
      practice more comprehensively that has been possible in the past. If implemented
      appropriately, occurrence screening eliminates the random efforts and audits of
      past quality assurance efforts with a systematic and comprehensive monitoring
      process aimed at identifying questionable quality of care practices. This article
      discusses the concept of occurrence screening as a useful tool in assessing
      quality of care in a special care unit.

PMID- 1995011
TI  - Cardiac pacing in children.
AB  - Advances in pacemaker technology over the last 25 years have made cardiac pacing
      in infants and children a safe and practical therapy. Some of the technical
      challenges encountered with the first permanent pacemaker implantation in
      children during the early 1960s have been solved with miniaturized generators,
      lithium batteries, noninvasive programmability, and improved placement
      techniques. This chapter reports common causes of bradydysrhythmias in children,
      reviews the indications for permanent pacemaker implantation in children,
      describes current pacing systems appropriate for children, and identifies nursing
      implications and potential pacemaker complications unique to children.

PMID- 1995012
TI  - Electrocardiographic interpretation of pacemaker rhythms.
AB  - The interpretation of electronic pacemaker rhythm strips requires attention to
      detail to determine the appropriate function of a pacemaker. Often the clinician
      is faced with the admission of a patient who is either unknown to have a
      pacemaker, or the type of pacemaker is not immediately available to the
      practitioner. In such a situation, the practitioner must be able to use pre
      existing skills to determine the proper function of the pacemaker as well as any
      abnormalities in its pattern. This evaluation requires review of the inherent or
      underlying patient rhythm, the presenting pacemaker rhythm, and the relationship
      of the two. Additionally, in more sophisticated pacemakers, the relationship
      between the functions of the pacemaker also must be assessed. A variety of
      pacemaker rhythm examples are used to delineate the process involved in the
      determination of proper pacemaker function.

PMID- 1995013
TI  - Development of outcome standards in critical care.
AB  - The forces influencing the development of outcome standards are gaining momentum.
      These forces are professional nursing issues, accreditation standards, and
      reimbursement issues. Traditionally, structure and process measures provided the
      means for evaluating the quality of nursing care. But nurses also play an
      important role in achieving positive patient outcomes. Outcome standards provide
      a mechanism for measuring patient outcomes. In 1990 the American Association of
      Critical-Care Nurses (AACN) published Outcome Standards for Nursing Care of the
      Critically Ill. The book serves as a model for developing and using outcome
      standards in critical care units. This chapter describes these outcome standards
      and recommends ways to use them. The Joint Commission on the Accreditation of
      Healthcare Organizations' (JCAHO) ten-step model outlines development of unit
      specific outcome standards. Methods focus throughout on a quality assurance
      framework.

PMID- 1995014
TI  - Monitoring and evaluation in the special care unit: the JCAHO ten-step process.
AB  - Monitoring and evaluating the quality and appropriateness of patient care in the
      special care unit is the basis for quality assurance activities. To make the
      monitoring and evaluation process helpful, health care professionals in special
      care units must be involved in each step of the process. The focus must be on
      patient care, specifically on clinical aspects of care rather than on structural
      specifications or technical processes. In addition to assisting the special care
      unit to meet accreditation requirements, ongoing monitoring and evaluation assist
      that unit to assure high-quality care. Monitoring and evaluation activities also
      assist the special care unit manager in responding to demands of state and
      federal regulators by providing an objective assessment of the care provided to
      Medicare and Medicaid patients. These activities also can provide assistance in
      responding to concerns about lawsuits involving alleged negligence in provision
      of special care; and in meeting pressures from third-party payers to reduce costs
      associated with unnecessary treatment in special care units. This chapter
      describes how the ten-step monitoring and evaluation process can be used to help
      assure high-quality patient care in the special care unit.

PMID- 1995015
TI  - Implementation of structure and process standards.
AB  - A dilemma in critical care nursing practice is how to develop and implement a
      practical quality assurance program that incorporates high-quality standards of
      nursing care for critically ill patients and addresses those aspects of care
      considered important by the Joint Commission on Accreditation of Healthcare
      Organizations (JCAHO). Standards for Nursing Care of the Critically Ill defines
      and describes structure and process standards and provides a comprehensive guide
      for the development of a program for the delivery of quality care to critically
      ill patients. The purpose of this chapter is to discuss practical application of
      the standards described by the American Association of Critical-Care Nurses
      (AACN) through the use of policies and procedures that support structure and
      process standards.

PMID- 1995016
TI  - The quality assurance process in critical care education.
AB  - The American Association of Critical-Care Nurses (AACN) has developed education
      standards for critical care nursing. These structure and process standards can be
      used as part of the Joint Commission on Accreditation of Healthcare
      Organizations' (JCAHO) ten-step process for monitoring and evaluating critical
      care education programs. This chapter discusses the application of the monitoring
      and evaluation process, based on education standards, for critical care education
      programs.

PMID- 1995017
TI  - A unit-based approach to outcome centered nursing quality assurance in critical
      care.
AB  - This chapter describes a unit-based nursing quality assurance program in critical
      care. It outlines a unit-based structure, implementation of the Joint Commission
      on Accreditation of Healthcare Organizations (JCAHO) ten steps and joint
      nurse/physician outcome indicators.

PMID- 1995018
TI  - Quality assurance: monitors in special care.
AB  - Special care units need to establish economically feasible and meaningful
      monitors to evaluate patient care needs. High-cost areas, such as special care,
      monitor appropriate use of resources in high-risk, high-volume, and problem-prone
      areas. The monitoring process needs to provide information regarding the quality
      of care in the special care unit without greatly decreasing time spent by staff
      in direct patient care. This chapter discusses development of efficient
      monitoring tools for quality assurance indicators in the special care unit.

PMID- 1995019
TI  - Patient education as a quality indicator in critical care: ischemic heart disease
      -recognition and response.
AB  - Medical critical care unit (MCCU) nurses at a VA medical center designed a
      quality assurance monitor for educating cardiac patients. Patients with a
      diagnosis of rule-out myocardial infarction are interviewed about their
      preadmission use of nitroglycerin and entry into emergency treatment facilities.
      The MCCU nurses teach a five-point "ischemic heart disease--recognition and
      response" lesson, and ascertain the patient's immediate level of understanding.
      If the patient returns to the MCCU at a later date, nurses record the
      appropriateness of his use of nitroglycerin and entry into emergency treatment
      facilities. Thus, both short- and long-term gains in patient knowledge are
      assessed. Solutions to problems encountered in the quality assurance monitor
      implementation process are discussed. Benefits of the project to patients, the
      nursing department, and other departments are identified. A sample monthly report
      and the monitor data collection tool illustrate the process. Future directions
      for patient education efforts in the MCCU are outlined.

PMID- 1995020
TI  - Standards of care: integrating nursing care plans and quality assurance
      activities.
AB  - Traditionally, standards are used to define the level of care that a patient can
      expect to receive in a given institution or on a given nursing unit. These
      standards are the foundation of quality assurance programs. Unfortunately, with
      the increased emphasis on monitoring care, many standards are being written after
      the quality assurance activities have been developed and are in place. Often,
      standards are placed neatly in a book that is dusted off and brought out when the
      Joint Commission for Accreditation of Healthcare Organizations representative
      (JCAHO) visits. The nursing staff at the unit level has no real knowledge or
      understanding of the standards. This may result in a nonfunctioning quality
      assurance program.

PMID- 1995021
TI  - Implementing a quality assurance program at the unit level in intensive care:
      essential elements for successful implementation.
AB  - Implementing a quality assurance program at the unit level in intensive care can
      be accomplished smoothly if certain key elements are included in the
      implementation process. For the program to be successful, all of these elements
      are essential.

PMID- 1995022
TI  - Quality monitor implementation for standards of care of the mechanically
      ventilated patient.
AB  - Each critical care unit has a responsibility to develop a quality assurance
      process to evaluate nursing practice. Staff members at Shawnee Mission Medical
      Center (SMMC) developed a protocol, based on the Marker Model, to establish
      standards of care related to care of the patient requiring mechanical
      ventilation. The quality assurance process used to monitor implementation of the
      standards is described.

PMID- 1995023
TI  - Quality assurance to quality improvement: the impact of the agenda for changes.
AB  - Health care professionals are committed to the continual improvement of the
      quality of patient care. The Joint Commission on the Accreditation of Healthcare
      Organizations (JCAHO) has launched a major research and development project
      intended to improve its ability to evaluate health care organizations and
      encourage greater attention to the quality of daily patient care. This chapter
      describes JCAHO's challenge to evaluate capability and performance of health care
      organizations and practitioners. The intent of JCAHO's agenda for change is to
      focus on patient outcomes and quality improvement through a more precise and
      objective evaluation of both clinical and managerial performance. Through the
      agenda for change, JCAHO and the health care organization will participate in a
      continuous-flow monitoring system in which clinical and organizational data are
      transmitted from the field to JCAHO, analyzed, and fed back to the health care
      organization.

PMID- 1995024
TI  - Standards of care and practice: a vital link in quality assurance.
AB  - In the critical care unit setting, a quality assurance program is based on the
      Joint Commission on the Accreditation of Healthcare Organizations (JCAHO) ten
      step model for monitoring and evaluation. The addition of nursing standards of
      patient care and standards of nursing practice to that ten-step model provides
      the vital link between patient expectations, staff performance, and quality
      assurance in that unit.

PMID- 1995025
TI  - Cardiac pacemakers.

PMID- 1995026
TI  - Pacemaker technology: an overview.
AB  - Cardiac pacing has evolved considerably over the past 30 years. Early pacemakers
      were nonprogrammable asynchronous devices which prevented asystole, syncope, and
      death. The current generation of implantable devices is much more sophisticated.
      With multiprogrammable features, these devices are intended not only to save life
      but also to improve the quality of life. This chapter reviews the pacemaker mode
      code, indications, electronic circuitry, power sources, and
      programmable/telemetry features of current devices.

PMID- 1995027
TI  - Trifluoperazine modulation of resistance to the topoisomerase II inhibitor
      etoposide in doxorubicin resistant L1210 murine leukemia cells.
AB  - Murine leukemia L1210 cells selected for progressive resistance to doxorubicin
      (DOX) display both the multidrug resistant (MDR) phenotype and reductions in drug
      induced topoisomerase II-mediated DNA cleavage in nuclear extracts (Ganapathi,
      R.; Grabowski, D.; Ford, J.; Heiss, C.; Kerrigan, D.; Pommier, Y., Cancer Commun.
      1:217-224; 1989). The present study was performed to characterize the results of
      exposure of the sensitive (S) and progressively DOX-resistant (10-fold, R1, and
      40-fold, R2) L1210 cells to the topoisomerase II inhibitor, etoposide, and to
      investigate the modulating effects of the calmodulin inhibitor, trifluoperazine
      (TFP). Immunoblotting experiments indicated no apparent decrease in the p170 or
      p180 isoforms of topoisomerase II in the resistant sublines versus parental
      sensitive cells. Cross-resistance to etoposide (VP-16) was similar to that of DOX
      (10- and 40-fold). A non-cytotoxic concentration of 5 microM TFP enhanced cell
      kill 1.5- fold in the sensitive and 3- to 5-fold in the progressively DOX
      resistant cells. Accumulation of VP-16 was 30% to 50% lower in the resistant
      sublines versus similarly treated sensitive cells, and a marked enhancement of
      drug uptake in the presence of TFP was observed in the sensitive but not in the
      resistant cells exposed to equivalent extracellular levels of VP-16. Although
      equimolar concentrations of VP-16 produced fewer DNA single strand breaks (SSB)
      and DNA protein crosslinks (DPC) in the resistant versus sensitive cells, similar
      DNA damage was apparent when S and R1, but not R2, cells were treated at VP-16
      concentrations that produced equivalent cell death.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1995028
TI  - Cytotoxicity of tetraplatin and cisplatin for human and rodent cell lines
      cultured as monolayers and multicellular spheroids.
AB  - The cytotoxicity of tetraplatin (dl-trans), its d- and l-isomers, and cisplatin
      for four human tumor cell lines (myeloma 8226, ovarian 2008, A2780, and OVCAR-3),
      their cisplatin-resistant variants, and three rodent cell lines (V79, EMT6/Ro,
      and L1210) were compared. Tetraplatin was more, or equally as, potent as
      cisplatin for the human cell lines and for L1210 but was clearly less potent for
      V79 and EMT6/Ro. The d-trans tetraplatin was more potent than the l-trans.
      Cisplatin resistant human tumor cells were less resistant to tetraplatin. On
      comparing sensitivity of V79 and EMT6/Ro cells in two growth models, we observed
      that all of the platinum compounds were more cytotoxic to cells in multicellular
      spheroids than in exponentially growing monolayers. Uptake studies, however,
      showed that tetraplatin was more cytotoxic to spheroids because spheroids
      accumulated more drug than monolayers.

PMID- 1995029
TI  - Emended descriptions and recognition of Streptococcus constellatus, Streptococcus
      intermedius, and Streptococcus anginosus as distinct species.
AB  - Strains currently classified as Streptococcus anginosus include strains
      previously identified as Streptococcus constellatus (Prevot 1924) Holdeman and
      Moore 1974, Streptococcus intermedius (Prevot 1925), and "Streptococcus milleri"
      (Guthof 1956) because these specific epithets were argued to be later synonyms of
      Streptococcus anginosus (Andrewes and Horder 1906) Smith and Sherman 1938 by
      Coykendall et al. (Int. J. Syst. Bacteriol. 37:222-228, 1987). However, recent
      data from DNA-DNA hybridization experiments, whole-cell-derived polypeptide
      patterns determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis,
      and data from phenotypic testing have demonstrated that Streptococcus anginosus
      strains represent three readily identifiable taxa to which the previously
      assigned type strains of Streptococcus constellatus (strain NCDO 2226 [= ATCC
      27823], Streptococcus intermedius (strain NCDO 2227 [= ATCC 27335], and
      Streptococcus anginosus (strain NCTC 10713 [= ATCC 33397] have been shown to
      belong. Therefore, we propose recognition of Streptococcus constellatus (emend.)
      (type strain NCDO 2226 [= ATCC 27823]), Streptococcus intermedius (emend.) (type
      strain NCDO 2227 [= ATCC 27335]), and Streptococcus anginosus (emend.) (type
      strain NCTC 10713 [= ATCC 33397]) as distinct species and propose an emended
      description of each of these taxa.

PMID- 1995030
TI  - Staphylococcus capitis subsp. ureolyticus subsp. nov. from human skin.
AB  - A new subspecies, Staphylococcus capitis subsp. ureolyticus, was isolated from
      human skin and is described on the basis of studies of 15 to 26 strains. DNA-DNA
      reassociation reactions demonstrated that these strains were closely related to
      Staphylococcus capitis but were significantly divergent. The strains of S.
      capitis subsp. ureolyticus can be distinguished from S. capitis by their positive
      urease activity, their ability to produce acid from maltose under aerobic
      conditions, their fatty acid profile, and their colony morphology. The type
      strain of the new subspecies is strain ATCC 49326.

PMID- 1995031
TI  - Helicobacter nemestrinae sp. nov., a spiral bacterium found in the stomach of a
      pigtailed macaque (Macaca nemestrina)
AB  - A new microaerophilic, spirally curved, rod-shaped bacterium was isolated from
      the gastric mucosa of a pigtailed macaque (Macaca nemestrina). The gram-negative
      cells of this bacterium are oxidase, catalase, and urease positive and strongly
      resemble Helicobacter pylori (Campylobacter pylori) cells. Like H. pylori, this
      organism does not metabolize glucose, does not reduce nitrate or produce indole,
      does not produce H2S from triple sugar iron agar, does not hydrolyze hippurate or
      esculin, and does not grow in the presence of 1% glycine, 1.5% salt, or 1% bile.
      Also like H. pylori, it is resistant to nalidixic acid and susceptible to
      cephalothin. However, unlike H. pylori, the colorless colonies are flat and have
      irregular edges. This organism has a unique cellular fatty acid composition,
      forming a new gas-liquid chromatography group, group K, and a distinctive DNA
      content (24 mol% guanine plus cytosine). It exhibits less than 10% DNA-DNA
      homology (as determined by the nylon filter blot method at 65 degrees C) with
      other members of the genus Helicobacter. Although the levels of DNA relatedness
      between previously described Helicobacter species and the new organism are low
      (less than 10%) and the difference in guanine-plus-cytosine content is large (24
      versus 36 to 41 mol%), the genus Helicobacter is the only genus in which it is
      logical to include the organism at this time. We propose that our single strain
      represents a new species, Helicobacter nemestrinae, and we designate strain
      T81213-NTB (= ATCC 49396) as the type strain.

PMID- 1995032
TI  - Bifidobacterium ruminantium sp. nov. and Bifidobacterium merycicum sp. nov. from
      the rumens of cattle.
AB  - Among several hundred bifidobacteria isolated from bovine rumens, eight strains
      were recognized primarily on the basis of DNA-DNA hybridization results as
      members of two new distinct DNA homology groups. We studied the morphology,
      oxygen, carbon dioxide, temperature, and pH requirements, fermentation patterns,
      end products of glucose fermentation, biochemical reactions, protein
      electrophoretic patterns, isozyme patterns, DNA homology relationships, and
      guanine-plus-cytosine contents of these organisms, and we propose that these two
      groups of strains should be considered new species, Bifidobacterium ruminantium
      (type strain, strain ATCC 49390) and Bifidobacterium merycicum (type strain,
      strain ATCC 49391).

PMID- 1995033
TI  - Mycoplasma oxoniensis, a new species isolated from Chinese hamster conjunctivas.
AB  - Mycoplasmas which were distinct from Mycoplasma cricetuli were isolated from the
      conjunctivas of Chinese hamsters. Two clones, which were derived from a single
      colony and were obtained on separate occasions, were examined in detail for
      morphology, growth, and biochemical characteristics. These clones were
      indistinguishable from each other and had the following properties: guanine-plus
      cytosine content of 29 mol%, requirement for sterol, facultatively anaerobic, and
      positive for glucose metabolism. They were serologically distinct from M.
      cricetuli and all 94 other previously described Mycoplasma and Acholeplasma spp.
      One of them, strain 128 (= NCTC 11712), is designated the type strain of a new
      species, Mycoplasma oxoniensis.

PMID- 1995034
TI  - Mycoplasma phocarhinis sp. nov. and Mycoplasma phocacerebrale sp. nov., two new
      species from harbor seals (Phoca vitulina L.).
AB  - A total of 120 mycoplasma strains were recovered from 97 of 265 diseased seals
      investigated during the seal epidemic in the North Sea and in the Baltic Sea in
      1988. Mycoplasmas were isolated from the respiratory tracts (including lungs),
      hearts, brains, and eyes of the seals. Thirty strains were filter cloned and
      investigated for their morphological, biochemical, and serological
      characteristics compared with the characteristics of previously described
      species. The results of an indirect immunofluorescence test, a growth inhibition
      test, and an immunobinding assay showed that these strains belong to two new
      species, for which the names Mycoplasma phocarhinis and Mycoplasma phocacerebrale
      are proposed. M. phocarhinis (17 strains) did not ferment glucose or hydrolyze
      arginine but did reduce tetrazolium chloride and potassium tellurite and produced
      films and spots. M. phocacerebrale (13 strains) metabolized arginine but not
      glucose and produced phosphatase but did not reduce tetrazolium chloride and
      potassium tellurite. Both species lysed sheep erythrocytes but did not absorb
      sheep or guinea pig erythrocytes. The type strain of M. phocarhinis is strain 852
      (= ATCC 49639), and the type strain of M. phocacerebrale is strain 1049 (= ATCC
      49640).

PMID- 1995035
TI  - Injector for highly viscous silicone oil.
AB  - A syringe device for the injection and evacuation of highly viscous silicone oil
      was developed. The problem of removing the air interfering with these manoeuvres
      was solved by providing special outlets in the plunger and handle of a
      conventional glass syringe. A slightly modified commercial motor perfusor was
      chosen to power this device, which has proved to be good and fail-safe in more
      than 100 cases.

PMID- 1995036
TI  - Outcome of cataract surgery in central India: a longitudinal follow-up study.
AB  - An epidemiological follow-up study of patients who had intracapsular cataract
      extraction in a voluntary hospital and its associated eye camps in Central India
      has for the first time evaluated the outcome one year after surgery in terms of
      visual acuity, use of spectacles, and improvement in income and mobility. The
      findings indicate that under these fairly typical conditions, 92% of the cases
      have adequate vision of 6/18 or better one year after surgery. Information on
      high usage of spectacles and on considerable improvements in income and mobility
      after cataract surgery is also reported. The outcome for patients operated upon
      in eye camps was almost as favourable as for those operated upon in hospital.
      Although the small differences are not statistically significant, the comparative
      findings require cautious interpretation and give rise to the epidemiological
      issues which are briefly discussed in this paper.

PMID- 1995037
TI  - Recovery of the blood-aqueous barrier after cataract surgery.
AB  - Following extracapsular cataract and posterior chamber implant surgery the
      sequential recovery of the blood-aqueous barrier was measured by anterior segment
      fluorophotometry. Postoperatively 49 (69.0%) out of 71 eyes (71 patients) had
      recovered at a uniform rate, re-establishing a normal blood-aqueous barrier by
      the end of the three-month study. In these eyes recovery of the blood-aqueous
      barrier was unaffected by the use of preoperative indomethacin, the surgeon, the
      type of section, or the type of fixation of the implant. In eyes recovering
      normally after cataract surgery the rate of recovery of the blood-aqueous barrier
      can be expressed by a in the equation a = (y-b)/x, in which y is the logarithm of
      the anterior chamber fluorescence, x is the time after surgery, and b is a
      constant for each patient which is the anterior chamber fluorescence measured
      immediately after surgery. This normal rate of recovery provides a baseline from
      which to assess surgical technique or postoperative medication.

PMID- 1995038
TI  - Anisometropic and strabismic amblyopia in the age group 2 years and above: a
      prospective study of the results of treatment.
AB  - Forty-four children aged 2-9 years with strabismic and anisometropic amblyopia
      were prospectively followed up during amblyopia treatment. The efficacy of
      optimised treatment in terms of number of cured children, time to achieve cure,
      and rate of initial improvement of visual acuity was evaluated in relation to age
      at start of treatment, type and initial degree of amblyopia, and adherence to
      treatment regimen. Compliance with treatment was the most critical factor
      predicting a successful outcome. Among the compliant children 35 out of 36 were
      cured (visual acuity difference between amblyopic and non-amblyopic eyes not more
      than one line) within five months regardless of age, treatment regimen, and type
      or initial degree of amblyopia as compared with none in the group with low
      compliance. Most of these compliant children were cured within three months, with
      shorter treatment times on average for the younger children. The initial
      improvement of visual acuity was also faster at 2 years than at 4 years of age.
      Anisometropes with moderate amblyopia at the start of treatment were over
      represented in the group with low compliance. We conclude that early diagnosis of
      strabismus in combination with general population screening at the age of 4 to
      detect amblyopia caused by anisometropia or microstrabismus seems to be
      efficacious for the cure of most cases. The major factor in treatment failure was
      found to be inadequate adherence to the treatment regimen.

PMID- 1995039
TI  - Corneal sensitivity and correlations between decreased sensitivity and anterior
      segment pathology in ocular leprosy.
AB  - Leprosy is one of the leading causes of corneal hyposensitivity. In this article
      the corneal sensitivity of 143 leprosy patients was examined, and correlations
      between corneal hyposensitivity and anterior segment pathology were detected.
      Twenty four healthy volunteers were examined as controls. Various degrees of
      corneal loss of sensitivity were found in 46.2% of leprosy patients.
      Lagophthalmos, chronic lepromatous granulomatous uveitis, iris atrophy, and
      social blindness were found 4.5-16.6 times more frequently in eyes which
      developed severe corneal hyposensitivity.

PMID- 1995040
TI  - Influence of untreated chronic plastic iridocyclitis on intraocular pressure in
      leprosy patients.
AB  - The intraocular pressures of a total of 286 eyes of patients with lepromatous and
      borderline lepromatous leprosy who never had regular ophthalmological care or
      local eye treatment were measured. The patients were categorised according to the
      type of leprosy they had, and the eyes were categorised as without or with
      chronic plastic iridocyclitis. In patients with lepromatous and borderline
      lepromatous types of leprosy the intraocular pressure was significantly lower in
      eyes with chronic plastic iridocylitis 10.1 (3.6) mmHg than in both unaffected
      eyes 11.0 (3.2) mmHg and control eyes 13.5 (2.5) mmHg. It has been shown that
      chronic plastic iridocyclitis which remains untreated for years results in a
      lower intraocular pressure than normal.

PMID- 1995041
TI  - The continuing challenge of ocular leprosy.

PMID- 1995042
TI  - Flecked retina associated with ring 17 chromosome.
AB  - We report the case of a mentally retarded male with a ring 17 chromosome who had
      subretinal drusen-like deposits in each eye. This is the second report of flecked
      retina in a patient with ring 17 chromosome, suggesting that there may be a
      causal relationship between abnormalities of chromosome 17 and retinal pigment
      epithelial or photoreceptor dysfunction.

PMID- 1995043
TI  - 'Cutting hook' modification of a standard 19 gauge green needle.

PMID- 1995044
TI  - The ocular pulse.

PMID- 1995045
TI  - Postural studies in pulsatile ocular blood flow: I. Ocular hypertension and
      normotension.
AB  - Measurements of pulsatile ocular blood flow (POBF) have been recorded in a group
      of healthy, ocular normotensive volunteers and ocular hypertensive patients
      recruited from outpatients. Use of a pneumotonometric probe linked to a Langham
      ocular blood flow system enabled readings of intraocular pressure and its
      variation with heart rate (ocular pulse) to be taken in erect and supine
      positions. Pulsatile ocular blood flow was calculated from these values by means
      of the pressure-volume relationship previously described for living human eyes.
      Assumption of the supine posture was accompanied by a significant rise in
      intraocular pressure; in normal eyes (mean, with SEM) (3.1 (0.4) mmHg, p less
      than 0.0001) and to a greater extent in ocular hypertensive eyes (4.7 (0.6) mmHg,
      p less than 0.0001). The POBF did not differ significantly between normotensive
      and ocular hypertensive groups in either the erect or supine postures. In both
      groups, however, assumption of the supine posture was accompanied by a
      significant fall in POBF (normals: -121 (21) microliters/min, p less than 0.0001;
      ocular hypertensives: -75 (16) microliters/min, p less than 0.0002). These
      reductions in POBF represent decrements of 27.5 (3.0)% and 17.1 (3.8)%
      respectively. Pulsatile ocular blood flow is reduced in the supine posture, and
      this may result in tissue hypoxia in subjects at risk of developing glaucoma. A
      companion paper describes the measurement of POBF in a group of patients with
      chronic open angle glaucoma treated with topical timolol 0.25%.

PMID- 1995046
TI  - Postural studies in pulsatile ocular blood flow: II. Chronic open angle glaucoma.
AB  - The pulsatile ocular blood flow (POBF) has been recorded in 15 patients with
      chronic open angle glaucoma. Measurements were performed during regular treatment
      with timolol 0.25% eyedrops, two weeks after withdrawal of this treatment, and
      then a further two weeks after its reinstitution. Readings were taken with
      subjects in both the erect and supine positions by means of a pneumotonometric
      probe to measure intraocular pressure (IOP), linked to a Langham ocular blood
      flow system. Assumption of the supine posture was associated with a significant
      increase in IOP in all phases of the study. Treatment with timolol lowered the
      mean IOP in comparison with the untreated phase (-4.4 (SEM 0.6) mmHg, p less than
      0.001) but had no effect on the postural change. A significant reduction in POBF
      was recorded on assumption of the supine posture (-66 (SEM 18) microliters/min, p
      less than 0.001), representing a mean decrement of 19%. However, there were no
      significant differences in POBF between treated and untreated phases of the
      study. Comparison of the values obtained in patients with glaucoma (COAG) after
      withdrawal of treatment with those in subjects with ocular hypertension revealed
      that there was no significant difference in intraocular pressure between the two
      groups. However, both POBF (-68 (SEM 29) microliters/min) and the pulse amplitude
      of the intraocular pressure (ocular pulse: -0.45 (SEM) 0.14 mmHg) were
      significantly lower in the COAG patients. Pulsatile ocular blood flow is
      significantly lower in patients with chronic open angle glaucoma. Furthermore,
      the POBF and the postural response of these patients is not improved by the use
      of topical timolol therapy.

PMID- 1995047
TI  - Seroprevalence of antibodies to HTLV-I in patients with ocular disorders.
AB  - Human T-lymphotropic virus type 1 (HTLV-I) has been shown to spread worldwide and
      to be responsible for distinct systemic diseases, namely adult T-cell leukaemia
      and HTLV-I-associated myelopathy. Immune-mediated, inflammatory lesions in the
      lungs, joints, and lacrimal glands (Sjogren's syndrome) are also suggested to be
      associated with the retrovirus. We studied seroprevalence of antibodies to HTLV-I
      in patients with various ocular disorders who are residents of south-west Japan,
      one of the endemic areas of HTLV-I. Of 310 patients with ocular disease 72
      (23.2%) were seropositive. This seroprevalence did not differ significantly from
      that of the general population of the area. As regards individual ocular
      diseases, aetiologically undefined nonspecific uveitis showed a significantly
      high seropositivity for HTLV-I. Of 44 patients 18 (40.9%) were seropositive.
      Their clinical features were acute or subacute, transient and sometimes
      recurrent, and granulomatous changes in the anterior uvea. Patients with isolated
      cotton-wool spot of the retina, non-familial retinitis pigmentosa, or
      keratoconjunctivitis sicca did not show any significantly high prevalence of HTLV
      I infection.

PMID- 1995048
TI  - Prognostic significance of the pattern visual evoked potential in ocular
      hypertension.
AB  - This paper reports a prospective study on 49 ocular hypertensive patients to
      evaluate the prognostic significance of transient abnormalities in the pattern
      visual evoked potential (VEP) in the development of glaucoma. Seven of 24
      patients with VEP abnormalities at diagnosis of ocular hypertension developed
      glaucomatous field defects in the follow-up period as compared with none of 25
      patients with normal VEPs at diagnosis. We conclude that appropriately designed
      pattern VEP testing is a valuable complement to careful (preferably computerised,
      static) perimetry. In addition, our findings support the contention that, in
      glaucomatous disease of the optic nerve, rudimentary pattern processing
      mechanisms--that is 'Y'-type units of the magnocellular pathways--may be affected
      earlier than luminance processing mechanisms.

PMID- 1995049
TI  - Ocular defects in infants of extremely low birth weight and low gestational age.
AB  - The eyes of 49 babies who weighed less than 1,000 g at birth or who were born at
      or before 28 weeks gestation were examined at the age of 4 years. Twenty-one
      children were normal. The remaining 29 children (59%) had ocular abnormalities
      which ranged from mild amblyopia to blindness from retinopathy of prematurity.
      The need to examine children at risk is stressed.

PMID- 1995050
TI  - Multifocal IOL implantation: 16 cases.
AB  - We interpreted the clinical data from 16 eyes with a 3M multifocal implant and
      compared them with data from 16 monofocal implants with the same follow-up
      period. The multifocal implant has several disadvantages: a lower initial visual
      acuity, a higher frequency of posterior synechiae, and slightly more difficult
      ophthalmoscopy than with conventional lenses. The great advantage of the
      multifocal implant is the good near visual acuity without additional correction.

PMID- 1995051
TI  - Effect of anaesthesia on intraocular blood flow.
AB  - Pulsatile ocular blood flow, intraocular pressure, systemic blood pressure, and
      heart rate was measured in two groups of 15 patients. One received lignocaine 1.5
      mg/kg intravenously prior to induction. There was a significant increase in
      intraocular pressure after suxamethonium, which was not associated with any rise
      in ocular blood flow. Both the IOP and ocular blood flow increased significantly
      after tracheal intubation. A rise in ocular blood flow reflects the stress
      response associated with intubation. Lignocaine failed to attenuate either
      response.

PMID- 1995053
TI  - Laser photocoagulation control of diabetic macular oedema without fluorescein
      angiography.
AB  - This study included 40 eyes in 22 diabetic patients with focal macular oedema.
      Laser photocoagulation was directed at decompensated or leaking microvascular
      lesions clinically detected without using pretreatment fluorescein angiograms.
      Post-treatment fluorescein angiograms performed after adequate clinical control
      of disease showed complete resolution of the macular oedema in 25 eyes (62.5%),
      whereas persistent leakage from microvascular lesions closer than 500 microns
      from the centre of the foveola was noted in 15 eyes (37.5%). These were
      clinically detected during the pretreatment examination and were found not to
      impair or threaten the patient's vision. Our data confirm the clinical impression
      that fluorescein angiography is not necessary for effective treatment and should
      be used only if necessary.

PMID- 1995052
TI  - Herpes simplex keratitis in renal transplant patients.
AB  - Five out of 430 patients (1.16%) undergoing kidney transplantation developed an
      atypical clinical picture of herpetic dendritic keratitis within four weeks after
      surgery. It was manifested by multiple dendrites, located mainly in the corneal
      periphery or the limbus, developing in relatively uninflamed eyes. The response
      to acyclovir therapy was prolonged and took at least three weeks. Additionally,
      subepithelial infiltrates with ultimate scarring developed in all patients.
      Disciform keratopathy was not found. This clinical course is ascribed to the
      patients' immunosuppressed state.

PMID- 1995054
TI  - Aminophospholipid molecular species asymmetry in the human erythrocyte plasma
      membrane.
AB  - The transbilayer distribution of the molecular species of aminophospholipids in
      human red blood cell plasma membrane has been investigated using a covalent
      labelling technique. Separation and quantitative analysis of the molecular
      species of phosphatidylethanolamine (PE) and phosphatidylserine (PS) was
      performed using high-performance liquid chromatography with UV detection of the
      trinitrophenyl derivatives obtained after reaction with trinitrobenzenesulfonic
      acid (TNBS). When the molecular species distribution obtained with intact cells
      was compared to that of the whole membrane, a molecular species asymmetry was
      evident. This phenomenon was most clearly evident when the reaction was performed
      at low temperatures (0 degrees C) and was obscured by the excessive labelling or
      probe permeation associated with higher temperatures or longer incubation times.
      The monoene species were enriched in the outer leaflet, they comprised about 30%
      of the PE species in this leaflet. The polyunsaturates were preferentially
      localized in the inner leaflet and this was true of the arachidonyl species in
      particular as they represented up to 35% of this pool. The w-3 polyunsaturated
      fatty acids displayed a preferential localization in the plasmalogen subclass in
      comparison to the diacyl fraction, i.e., they comprised about 58 of the former
      and 42% of the latter subclass of cellular PE w-3 species. Data concerning the
      separation, identification and quantification of PS molecular species in human
      erythrocytes is also presented. The internal localization of the polyunsaturated
      species as well as the compartmentalization of the w-3 and w-6 pools will have
      metabolic, structural and physical implications for membrane function.

PMID- 1995055
TI  - Dioxygen solubility in aqueous phosphatidylcholine dispersions.
AB  - The solubility of molecular oxygen, or dioxygen, in low weight percent (1.5%)
      sonicated dimyristoylphosphatidylcholine (DMPC) aqueous dispersions saturated
      with air has been measured as a function of temperature between 10 degrees C and
      40 degrees C. A modified Winkler technique was used involving a dual cell
      coulometric titration with voltammetric endpoint detection in a mixed solvent
      (methanol/water). The results indicate that dioxygen is approximately four times
      more soluble in the liquid crystalline bilayers (above 24 degrees C) than in the
      gel state bilayers (below 24 degrees C). The solubility of dioxygen in the
      bilayer does not appear to be strongly temperature dependent on either side of
      the 24 degrees C phase transition. The dioxygen solubility in gel state DMPC is
      approximately equal to that in water at the same temperature. Our result are
      contrasted with recent measurements made using EPR spin labels.

PMID- 1995056
TI  - Detection of structural defects in phosphatidylcholine membranes by small-angle
      neutron scattering. The cluster model of a lipid bilayer.
AB  - The oriented DPPC multilayers hydrated by D2O have been studied by a small-angle
      neutron scattering method in the Guinier range, and the gyration radius of the
      structural inhomogeneities has been estimated at about 29 A. They are interpreted
      as the annular defects between adjacent clusters uniting the all-trans chain
      'segments' adjacent to the polar head group regions. The angle of the 'segment'
      tilt is determined by the hydrated polar group area (59.2 A2 for DPPC bilayers)
      and has been estimated to be about 44 degrees under the given experimental
      conditions. The hydrocarbon interior of a bilayer can be suggested as a
      'sandwich' that is formed by two clustered layers (approx. 7 A of the thickness)
      and the central disordered (liquid) layer. The average cluster size along the
      bilayer surface is estimated to be approx. 24 A which correlates with the
      estimations of the short order region dimensions from the halfwidth of the X-ray
      'packing' reflex (4.6 A)-1. The average interchain separation of approx. 5 A and
      the average cross-section area of a chain in a cluster (21.4 A2) were estimated
      from the reflex position and the chain cross-section geometry. The total volume
      of defects and the fraction of a bilayer surface occupied by them were estimated
      too.

PMID- 1995057
TI  - Uptake of liposomes by cultured mouse bone marrow macrophages: influence of
      liposome composition and size.
AB  - A wide range of liposome compositions have previously been examined in vivo for
      their ability to affect the uptake of liposomes into cells of the
      reticuloendothelial (RE, mononuclear phagocyte) system (Allen, T.M. and Chonn, A.
      (1987) FEBS Lett. 223, 42-46; Allen et al. (1989) Biochim. Biophys. Acta 981, 27
      35). In this study we have examined the ability of cultured murine bone marrow
      macrophages to endocytose liposomes of various compositions and have looked for
      correlations between the in vivo and the in vitro observations. Compounds which
      substantially decreased RE uptake of liposomes in vivo, such as
      monosialoganglioside (GM1) and a novel synthetic lipid derivative of
      polyethyleneglycol (PEG-PE), also greatly decreased liposome uptake by bone
      marrow macrophages in a concentration-dependent manner. Lipids which increase
      bilayer rigidity, such as sphingomyelin (SM) and cholesterol (CHOL), decreased
      both in vivo and in vitro uptake of liposomes. Likewise, positive correlations
      were observed between the in vivo behavior of liposomes containing
      phosphatidylserine (PS) or various gangliosides and the ability of these
      liposomes to be taken up by bone marrow macrophages. Total liposome uptake by
      macrophages increased with incubation time at 37 degrees C while very little
      liposome association with the macrophages was observed at 4 degrees C. Liposome
      uptake increased with liposome concentration and for liposomes composed of egg
      phosphatidylcholine (PC) uptake plateaued at 40 nmol lipid per mg cell protein.
      There was an inverse correlation between liposome size of extruded large
      unilamellar vesicles and their uptake by macrophages.

PMID- 1995058
TI  - Peptide binding to lipid membranes. Spectroscopic studies on the insertion of a
      cyclic somatostatin analog into phospholipid bilayers.
AB  - The cyclic peptide SMS 201-995 (+)D-Phe1-Cys2-Phe3-D-Trp4-(+)Lys5-Thr6-++ +Cys7
      Thr(ol)8 is an analog of somatostatin and binds to lipid membranes by an
      electrostatic/hydrophobic mechanism. The structural changes accompanying the
      binding process were investigated with circular dichroism (CD), fluorescence
      spectroscopy, and phosphorus and deuterium nuclear magnetic resonance. The
      peptide penetrates into the lipid bilayer and the binding is accompanied by a
      small change in the CD spectrum suggesting the formation of beta-ordered
      structures. The fluorescence emission spectrum of the tryptophan side chain
      exhibits a blue shift and an intensity enhancement of the emission maximum,
      providing evidence that this residue is located in the inner part of the
      phospholipid headgroup region with a dielectric constant of epsilon approximately
      7. The peptide diffuses rapidly in the plane of the membrane, changing the lipid
      headgroup conformation. This was demonstrated by selectively deuterating the two
      choline segments and measuring the deuterium spectra as a function of the bound
      peptide concentrations. A linear variation of the quadrupole splitting with the
      mol fraction of bound peptide was observed. The molecular origin of this effect
      is a distinct change in the orientation of the phosphocholine dipole, moving the
      N+ end of the dipole away from the membrane surface into the water phase. This
      type of headgroup rotation appears to be the general response of the zwitterionic
      phosphocholine headgroup to cationic surface charges. However, peptides appear to
      be the most efficient modulators of the lipid headgroup structure known to date.

PMID- 1995059
TI  - Low potassium-type but not high potassium-type sheep red blood cells show passive
      K+ transport induced by low ionic strength.
AB  - Low potassium-type (LK) sheep red blood cells show a significant increase of the
      residual (i.e., ouabain-insensitive) K+ influx when the ionic strength of the
      solution is decreased. This effect is absent from high potassium-type (HK) sheep
      red blood cells. The KCl cotransport system is not involved since three different
      manoeuvres to suppress the KCl cotransport (replacement of Cl- by NO3-, volume
      decrease, inhibition by anti-L1 antibodies) have no effect on the low ionic
      strength-stimulated K+ influx.

PMID- 1995060
TI  - Nucleoside and nucleotide transport through a model liquid membrane. Periodic
      catastrophic transport of a novel amantadine phosphoramidate conjugate of 5'-AMP.
AB  - Adenosine 5'-phosphor(adamantyl)amidate (5), an analog derived by linking the
      antiviral drug amantadine to 5'-AMP is transported through a model membrane
      system in a discontinuous periodic-catastrophic fashion. The system was composed
      of a glass cell containing two aqueous buffer phases separated by a chloroform
      layer. A more lipophilic, but structurally related derivative, adenosine 5'
      phosphor(n-decyl)amidate (3) showed linear transport in the same system. Less
      lipophilic substances, including 5'-AMP and adenosine 5'
      phosphor(morpholidyl)amidate (2), did not show transport. It is hypothesized that
      the periodic-catastrophic transport is a result of the collective activity of
      amidate 5 at the interface between the first aqueous interface and the chloroform
      layer. The time between catastrophic events is thought to be a reflection of the
      time necessary for molecular organization at the interface. The phenomenon is a
      new example of molecular organization in a system far from equilibrium leading to
      a repetitive dynamic process.

PMID- 1995062
TI  - Activation of protein kinase C is essential for sustained insulin secretion in
      response to cholinergic stimulation.
AB  - Insulin secretion from isolated rat islets of Langerhans is enhanced by
      cholinergic agonists, such as carbachol (CCh), in the presence of a stimulatory
      concentration of glucose. Depletion of islet protein kinase C activity by
      prolonged exposure to a tumour-promoting phorbol ester did not prevent the
      initial secretory response to CCh, but markedly reduced the duration of CCh
      induced elevated secretory rates. These results suggest that the major action of
      PKC is in maintaining rather than initiating the insulin secretory response to
      cholinergic agonists.

PMID- 1995061
TI  - Thimerosal induces calcium mobilization, fructose 2,6-bisphosphate synthesis and
      cytoplasmic alkalinization in rat thymus lymphocytes.
AB  - The effect of thimerosal on intracellular calcium ([Ca2+]i), pH (pHi) and
      fructose 2,6-bisphosphate (Fru 2,6-P2) in thymus lymphocytes was investigated.
      The effect of thimerosal on cell growth was also examined. Thimerosal produced a
      dose-dependent increase in [Ca2+]i, pHi and in the level of fructose 2,6
      bisphosphate. Thimerosal was, however, unable to produce cell proliferation and
      inhibited [3H]thymidine incorporation when cells were challenged with PHA and
      costimulator. In the absence of external calcium, thimerosal produced only a
      slight increase in [Ca2+]i. In Na(+)-containing buffer, thimerosal induced an
      initial acidification (0.05 +/- 0.01 pH units), followed by an alkalinization of
      0.08 pH units/min, whereas in Na(+)-free media, pHi decreased 0.2 +/- 0.02 units
      and this acidification was maintained for more than 40 min. When external calcium
      was removed the initial acidification was unchanged and no further increase in
      pHi was observed. Polymyxin B, an inhibitor of protein kinase C, did not modify
      the initial thimerosal-induced acidification although pH returned to basal levels
      after 10 min. It was concluded that alkalinization induced by thimerosal is
      probably due to activation of the Na+/H+ exchanger and that changes in internal
      Ca2+, pH and metabolic rate are not sufficient to induce cellular proliferation.
      The mechanism by which thimerosal inhibits thymocyte proliferation remains to be
      clarified.

PMID- 1995063
TI  - Stimulation by NaCl, polylysine and heparin of two forms of spleen tyrosine
      protein kinase immunologically related with the protein expressed by lyn
      oncogene.
AB  - The previously isolated spleen tyrosine protein kinase, conventionally termed TPK
      IIA, displaying activation by either positively or negatively charged
      polyelectrolytes has been further characterized. TPK-IIA is immunologically
      related with the tyrosine protein kinase encoded by the lyn gene, a member of src
      subfamily and is dramatically activated by very high NaCl concentration. The
      stimulatory effects of NaCl and polylysine, which are not additive, are accounted
      for by increased Vmax values, the Km being virtually unchanged, suggesting that
      both effectors probably interact with the same site(s). Stimulation of TPK-IIA by
      heparin appears to be partially additive to that promoted by NaCl and possibly
      occurring through a different mechanism. The NaCl activatory effect correlates
      with the electrolytic nature of synthetic peptides used as substrates, being much
      more consistent with neutral peptides as compared with acidic ones. Of the other
      three spleen tyrosine protein kinases, TPK-I shows similar biochemical and
      immunological features, suggestive of close relatedness with TPK-IIA, while TPK
      IIB and TPK-III are neither related with the lyn protein nor with the products of
      three other oncogenes of the src subfamily, namely lck, hck and fyn.

PMID- 1995064
TI  - Deoxyadenosine-resistant human T lymphoblasts with elevated 5'-nucleotidase
      activity.
AB  - Although several different enzymes with 5'-nucleotidase activity have been
      described in mammalian cells, their functions in nucleotide metabolism have not
      been clearly distinguished. In the present experiments, a mutant human T
      lymphoblastoid cell line (CEM-dAdoR) was selected specifically for resistance to
      deoxyadenosine toxicity. Compared to parental CEM cells, the variant had 4-fold
      elevated ATP-activated cytosolic 5'-nucleotidase activity. Other enzymes of
      potential importance for deoxyadenosine metabolism were indistinguishable in the
      two cell types. In medium supplemented with the adenosine deaminase inhibitor
      deoxycoformycin, the T cells with increased 5'-nucleotidase accumulated less
      nucleotides from exogenously added deoxyadenosine, or 9-beta-D
      arabinofuranosyladenine, than did parental T lymphocytes. These metabolic changes
      were associated with resistance to the growth inhibitory effects of these
      nucleosides, and also to deoxyguanosine and to 9-beta-D-arabinofuranosylguanine.
      The T cells with elevated 5'-nucleotidase activity formed more 2',3'
      dideoxyadenosine than did parental cells, in deoxycoformycin-supplemented medium.
      The accumulation of 2',3'-dideoxyadenosine 5'-triphosphate from 2',3'
      dideoxyinosine was similarly augmented in the mutant. These data establish the
      importance of the cytosolic 5'-nucleotidase for the metabolism of purine 2'
      deoxyribonucleosides, arabinonucleosides and 2',3'-dideoxyribonucleosides in T
      lymphoblasts.

PMID- 1995065
TI  - Determination of the osmotic active drug concentration in the cytoplasm of
      anthracycline-resistant and -sensitive K562 cells.
AB  - A fluorescence method was used to follow the interaction of 4'-o
      tetrahydropyranyladriamycin (THP-ADR) with drug-resistant and -sensitive K562
      cells. The amounts of drug bound to the nuclei at the steady state, Cn and at the
      equilibrium state, CN, once the membrane has been solubilized with Triton X-100,
      have been determined as a function of the pH outside the cells (pHe): Cn
      increased and CN decreased as pHe increased. At a given pH value outside the
      cells, CN is the same for both sensitive and resistant cells, whereas Cn is lower
      in resistant cells as compared to sensitive cells. Using the observation that the
      essential binding characteristics of THP-ADR in nuclei are the same for both
      types of cell, the osmotic active drug concentration, Ci, in the cytoplasm of the
      cells was determined at different values of pHe. Using fluorescent dye, the
      cytoplasmic pH was determined and found equal to 7.2 +/- 0.1 in both types of
      cell. In sensitive cells, the equilibrium transmembrane concentrations verified
      the relation [DH+]i/[DH+]e = [H +]i/[H+]e where [DH +]i and [DH +]e stand for the
      concentration of protonated form of the drug inside and outside the cells,
      respectively. This indicates that the uptake of the drug occurs through free
      permeation of the neutral form of the drug in response to delta pH gradient. Such
      a relation is not verified in the case of resistant cells.

PMID- 1995066
TI  - The effect of bile salts on human vascular endothelial cells.
AB  - The uptake and release of radiochromium from adult human vascular endothelial
      cells in culture was employed to determine the relative toxicity of different
      bile salts. Endothelial cells after pre-incubation with 51Cr for 18 h were
      incubated with bile salts for 24 h and percentage chromium release was taken as a
      measure of toxicity to cells. Lithocholic acid (LC) (potassium salt) was
      cytotoxic at concentrations greater than 50 microM. However, LC glucuronide,
      sulfate and the beta-epimer were progressively less toxic with toxicity seen at
      concentrations of 60, 110 and 180 microM, respectively. The greatest cytotoxic
      effect was observed with glycolithocholic acid (GLC) (potassium salt) which was
      toxic at every concentration tested (20-200 microM). Sulfation abolished the
      toxic effect of GLC. At the concentrations employed for the assay (between 20 and
      240 microM) GLC sulfate (disodium salt), taurolithocholic acid sulfate (disodium
      salt), cholic acid (sodium salt), glycocholic acid (sodium salt), deoxycholic
      acid (sodium salt) and ursodeoxycholic acid (sodium salt) were not cytotoxic. The
      51Cr release cytotoxicity assay was validated with lactate dehydrogenase leakage
      from endothelial cells with a good correlation (r = 0.87). These data confirm in
      a human cellular system that LC and its conjugates were the most toxic of the
      bile salts tested and explains its pathophysiological importance in hepatobiliary
      disease. It also suggests that biotransformation by either sulfation or beta
      epimerisation of bile salts especially of LC, as occurs in patients with
      intrahepatic or extrahepatic biliary obstruction or severe cholestasis, is
      hepatoprotective.

PMID- 1995067
TI  - ADP-ribosylation in Clostridium difficile toxin-treated cells is not related to
      cytopathogenicity of toxin B.
AB  - ADP-ribosylation of a protein in human fibroblasts treated with partially
      purified Clostridium difficile toxin B was previously reported. Here we show that
      the same protein was ADP-ribosylated also in human fibroblasts exposed to
      supernatant from a C. difficile strain producing neither toxin A nor toxin B.
      Furthermore, in Chinese hamster ovary and in Vero cells, showing toxin B-induced
      cytopathogenic effect, the protein was not significantly ADP-ribosylated. The
      results indicate that the ADP-ribosylation is unrelated to the cytopathogenic
      effect of toxin B. It appears to be caused by another unidentified factor from C.
      difficile, and the substrate may correspond to a protein modified endogenously in
      cells exposed to stressful situations. Cellular actin was not ADP-ribosylated by
      toxin B.

PMID- 1995068
TI  - Receptors for modified low-density lipoproteins on human endothelial cells:
      different recognition for acetylated low-density lipoprotein and oxidized low
      density lipoprotein.
AB  - We examined the uptake pathway of acetylated low-density lipoprotein and
      oxidatively modified LDL (oxidized LDL) in human umbilical vein endothelial cells
      in culture. Proteolytic degradation of 125I-labeled Ac-LDL or Ox-LDL in the
      confluent monolayer of human endothelial cells was time-dependent and showed
      saturation kinetics in the dose-response relationship, which suggests that their
      incorporation is receptor-mediated. Cross-competition studies between acetylated
      LDL and oxidized LDL showed that the degradation of 125I-labeled acetylated LDL
      was almost completely inhibited by excess amount of unlabeled acetylated LDL,
      while only partially inhibited by excess unlabeled oxidized LDL. On the other
      hand, the degradation of 125I-labeled oxidized LDL was equally inhibited by
      excess amount of either acetylated or oxidized LDL. Cross-competition results of
      the cell-association assay paralleled the results shown in the degradation assay.
      These data indicate that human endothelial cells do not have any additional
      receptors specific only for oxidized LDL. On the contrary, they may have
      additional receptors, as we previously indicated on mouse macrophages, which
      recognize acetylated LDL, but not oxidized LDL.

PMID- 1995069
TI  - The 38 kDa Ca2+/membrane-binding protein of pig granulocytes needs a high Ca2+
      concentration to be phosphorylated by protein kinase C.
AB  - The 38 kDa Ca2+/membrane-binding protein reported to be the dominant substrate of
      protein kinase C in the extracts of pig neutrophil granulocytes was purified
      partially and its phosphorylation was investigated. In pig granulocytes type II
      protein kinase C was the major isoform, while type III isoenzyme was present only
      as a minor activity. Phosphorylation of the 38 kDa protein was performed with rat
      brain protein kinase C. Each of the three isoenzymes purified from rat brain was
      able to phosphorylate this protein, though on the conditions used in our
      experiments it was phosphorylated most intensively by type II protein kinase C. A
      phospholipid-dependent, but Ca2(+)-independent, form of protein kinase C was
      demonstrated with the aid of a synthetic oligopeptide substrate. Phosphorylation
      of the 38 kDa protein by the Ca2(+)-independent enzyme proceeded exclusively in
      the presence of Ca2+. The Ca2+ concentration necessary for the phosphorylation of
      the 38 kDa by either form of protein kinase C was by orders of magnitude higher
      than that required for the activation of protein kinase C.

PMID- 1995070
TI  - Excitation and detection of action potential-induced fluorescence changes through
      a single monomode optical fiber.
AB  - An optical probe capable of detecting intracellular potential changes in
      individual cells, in vitro, which has the potential for in vivo applications, has
      been developed. A single-mode optical fiber directs laser light onto cells
      stained with the voltage-sensitive fluorescent dye, WW781 and also returns part
      of the resulting fluorescence to a detection system. Frog cardiac cells in vitro
      were used in these initial experiments. The fractional change in fluorescent
      intensity of 10(-3) for a 50 mV shift in transmembrane potential obtained from a
      heart immobilized in zero calcium Ringer's solution is comparable to that
      reported for other optical methods. For hearts in normal calcium Ringer's
      solutions, very large reproducible motion related artifacts were detected.

PMID- 1995071
TI  - Glucocorticoids inhibit fructose 2,6-bisphosphate synthesis in rat thymocytes.
      Opposite effect of cycloheximide.
AB  - The content of fructose 2,6-bisphosphate (Fru(2,6)P2) and lactate production in
      triamcinolone acetonide-treated rats thymocytes was studied. The effect in vitro
      of corticosterone and dexamethasone on normal thymocytes was also examined.
      Glucocorticoids produced a marked decrease in Fru(2,5)P2 content and lactate
      production. The largest effect was observed with triamcinolone acetonide (7.5 mg
      per kg body weight), which after 20 h of treatment produced over 90% of
      inhibition. This change was accompanied by the decrease of both
      phosphofructokinase-1 and -2 activities and ATP levels, without modifications of
      hexoses phosphate content. The inhibitory actions of glucocorticoids were
      abolished by cycloheximide, an inhibitor of protein synthesis. Furthermore this
      drug, by itself, increased Fru(2,6)P2 content by more than 50% compared with the
      controls.

PMID- 1995072
TI  - An FM3A mutant, G258, with a mutation that affects both cell growth and
      oligosaccharide-lipid synthesis.
AB  - I have previously isolated a temperature-sensitive FM3A mutant (G258) defective
      in asparagine-linked glycosylation. G258 shows not only the temperature
      sensitivity for cell growth, but also temperature sensitivity for synthesis of
      oligosaccharide-lipid (Nishikawa, Y. (1984) J. Cell. Physiol. 119, 260-266). In
      the present study, I isolated revertants for cell growth from G258 cells. All
      three growth revertants also showed reversion on the synthesis of oligosaccharide
      lipid. These results imply that the temperature sensitivity for oligosaccharide
      lipid synthesis of G258 couples with the temperature sensitivity for cell growth
      of the mutant. A possible mechanism of the coupling between impaired
      oligosaccharide-lipid synthesis and growth arrest of G258 cells at 39 degrees C
      is discussed.

PMID- 1995073
TI  - Studies of the mechanism of activation of HIT-T15 cells by lactate.
AB  - L-Lactate, D-lactate, propionate and acetate (all 20 mM) caused a marked
      intracellular acidification in HIT-T15 cells loaded with 2'7'-bis(carboxyethyl)
      5'(6')-carboxyfluorescein (BCECF), followed by recovery to more alkaline values.
      The effects of L- and D-lactate, but not propionate or acetate, were inhibited by
      5 mM alpha-fluorocinnamate. Both L- and D-lactate caused a marked depolarisation
      and rise in cytosolic [Ca2+] in HIT cells as assessed by oxonol-V and quin2
      fluorescence, respectively. Propionate had similar, though less marked, effects,
      whereas acetate exerted only a modest influence on membrane potential and
      cytosolic [Ca2+]. The rate of oxidation of L-lactate by HIT cells greatly
      exceeded that of D-lactate. alpha-Fluorocinnamate delayed, but did not prevent,
      the effects of L-lactate on HIT cell membrane potential or cytosolic [Ca2+]. L
      lactate diminished the rate of efflux of 86Rb+ from preloaded HIT cells.
      Inhibition of calcium- and nucleotide-sensitive K+ channels with
      tetraethylammonium and tolbutamide also reduced the 86Rb+ efflux rate, and
      prevented any further reduction in response to L-lactate. However, such
      inhibition of K+ channels did not prevent a further depolarisation and rise in
      cytosolic [Ca2+] upon the subsequent addition of lactate. It is suggested that
      the activation of HIT-T15 cells by lactate is not the result of intracellular
      acidification or increased metabolic flux, and does not require diminished K+
      permeability. An alternative mechanism is based upon the possible electrogenic
      flux of lactate across the plasma membrane.

PMID- 1995074
TI  - Volume regulation in mouse pancreatic beta-cells is mediated by a furosemide
      sensitive mechanism.
AB  - A possible role for loop diuretic-sensitive Cl-/cation cotransport in volume
      regulation in the pancreatic beta-cells was investigated by measuring 86Rb+
      efflux from beta-cell-rich pancreatic islets as well as the size of isolated beta
      cells under different osmotic conditions. Lowering the osmolarity to 262 mosM
      (83% of control) resulted in a rapid cell swelling which was followed by
      regulatory volume decrease (RVD). RVD was completely inhibited by furosemide (1
      mM), an inhibitor of Cl-/cation co-transport. The hypotonic medium (262 mosM)
      induced a rapid and strong increase in 86Rb+ efflux from beta-cell-rich mouse
      pancreatic islets and the furosemide-sensitive portion of the efflux was
      significantly increased. A slightly less hypotonic medium (285 mosM, 90% of
      control) induced only cell swelling and no RVD. With this medium only a marginal
      increase in 86Rb+ efflux was observed. Increasing the osmolarity by adding 50 mM
      NaCl (final osmolarity: 417 mosM, 132% of control) induced a rapid cell shrinkage
      but no regulatory volume increase (RVI). When the osmolarity was increased from a
      slightly hypotonic medium (262 mosM) to an isotonic medium (317 mosM) an initial
      cell shrinkage was followed by RVI. This RVI was inhibited by 1 mM furosemide.
      The data suggest that RVD as well as RVI in the beta-cells are mediated by loop
      diuretic-sensitive cotransport of chloride and cations and that these cells show
      a threshold for hypotonic stimulation of RVD.

PMID- 1995075
TI  - Changes in inositol transport during DMSO-induced differentiation of HL60 cells
      towards neutrophils.
AB  - [3H]Inositol uptake by HL60 cells was measured during DMSO-induced
      differentiation towards neutrophils. The values for Km (53.2 microM) and Vmax
      (5.3 pmol/min per 10(6) cells) obtained for control HL60 cells are in good
      agreement with previously published figures for this cell line. Inositol
      transport into HL60 cells was an active, saturable and specific process which was
      unaffected by extracellular glucose concentrations. Inositol transport rates
      changed during DMSO-induced differentiation of HL60 cells towards neutrophils. An
      increase in inositol transport rates occurred during the first 4 days of exposure
      to 0.9% DMSO and was concommitant with the period leading to growth arrest and
      prior to the acquisition of the differentiated phenotype. These changes preceded
      the rise in intracellular inositol concentration from 10.9 to 132.7 microM seen
      between day 1 and day 5. After 4 days exposure to DMSO the rate of inositol
      transport fell to a value of 3.2 +/- 0.3 pmol/min per 10(6) cells at day 7, this
      was accompanied by a small reduction in intracellular inositol from a peak value
      of 132.7 to 112 microM. The inositol transport rate, thus, appears to closely
      accompany changes in the intracellular concentration of inositol. Inositol
      transport in human peripheral blood neutrophils was an order of magnitude slower
      than the value for uninduced HL60 cells, but the Km for inositol transport was
      similar in both cell types and was unchanged during HL60 differentiation. This
      suggests that changes in inositol transport rate are achieved by the modulation
      of a commonly expressed inositol transporter, one consequence of which is the
      alteration of intracellular inositol concentrations.

PMID- 1995076
TI  - Flow cytometric characterization and sorting of cultured Brassica napus
      microspores.
AB  - A flow cytometric procedure was used to characterize and sort embryogenic
      Brassica napus microspore cultures. Embryogenic microspores continued to increase
      in size throughout the culture period and fluoresced when stained with
      fluoresecein diacetate (FDA). However, most of the cells in culture (greater than
      95%) lost their viability over the culture period and the correlation between the
      percentage viable cells in a culture and the productivity of the culture was not
      significant until day 3. By sorting large fluorescent cells on day 1 and day 3 of
      the culture period populations of cells that were 7-18-fold more embryogenic than
      sorted mixed cells were obtained. The flow cytometric procedure would be useful
      for rapidly assessing the effects of a large variety of culture and media
      conditions on embryogenesis is rapeseed microspore cultures. Furthermore, the
      populations of potentially embryogenic microspores isolated by flow cytometry
      might be useful for studies of the early cellular and molecular changes that
      occur during androgenesis in rapeseed.

PMID- 1995077
TI  - Cytotoxic effect and uptake mechanism by isolated rat hepatocytes of lithocholate
      and its glucuronide and sulfate.
AB  - The hepatotoxicity and uptake mechanism of lithocholate and its glucuronide and
      sulfate were studied using isolated rat hepatocytes. Cytotoxicity was in the
      order of lithocholate greater than lithocholate-glucuronide greater than
      lithocholate-sulfate; their 50% cytotoxic concentrations on hepatocytes were 50,
      150 and 700 microM, respectively. Thus, glucuronidation as well as sulfation
      acted to detoxify lithocholate, not relating to the previously reported higher
      cholestatic effect of lithocholate-glucuronide than lithocholate. Lithocholate
      uptake was linear up to 50 microM, whereas the uptakes of lithocholate
      glucuronide and sulfate were saturable with an apparent Km and Vmax of 32 microM
      and 6.4 nmol/min per 10(6) cells for lithocholate-glucuronide and 26 microM and
      11.8 nmol/min per 10(6) cells for lithocholate-sulfate. Na+ replacement by
      choline+ had no effect on the uptake of lithocholate and lithocholate
      glucuronide, whereas it slightly inhibited lithocholate-sulfate uptake.
      Lithocholate-glucuronide uptake was inhibited by lithocholate-sulfate and
      sulfobromophthalein, whereas lithocholate-glucuronide and sulfobromophthalein had
      no effect on lithocholate-sulfate uptake. These data indicate that hepatic
      lithocholate uptake is mediated by simple diffusion, and that hepatic uptake of
      lithocholate-glucuronide and sulfate is mainly mediated by a Na(+)-independent
      carrier.

PMID- 1995078
TI  - Biological activity of 1 alpha, 25-dihydroxyvitamin D derivatives--24-epi-1
      alpha, 25-dihydroxyvitamin D-2 and 1 alpha,25-dihydroxyvitamin D-7.
AB  - Biological activity of 24-epi-1 alpha,25-dihydroxyvitamin D-2 (24-epi
      1,25(OH)2D2) and 1 alpha,25-dihydroxyvitamin D-7 (1,25(OH)2D7), the 22,23-dihydro
      derivative of the former compound, was investigated. Both of the vitamin D
      derivatives stimulated intestinal calcium transport and calcium mobilization from
      bones in rats; however, the effect was about 50% of that of 1 alpha,25
      dihydroxyvitamin D-3 (1,25(OH)2D3). On the other hand, 24-epi-1,25(OH)2D2 and
      1,25(OH)2D7 inducement of HL-60 human leukemia cell differentiation was
      comparable to that of 1,25(OH)2D3. Accordingly, the differentiation-inducing
      activity of 24-epi-1,25(OH)2D2 and 1,25(OH)2D7 was much greater than their
      ability to stimulate calcium metabolism. In contrast to 1,25(OH)2D3, 24-epi
      1,25(OH)2D2 and 1,25(OH)2D7 exerted little hypercalcemic activity in mice. These
      results suggest that both vitamin D derivatives will be useful as anti-tumor
      agents.

PMID- 1995079
TI  - Effect of epidermal growth factor (EGF) on gluconeogenesis in isolated rat
      hepatocytes. Dependency on the red-ox state of the substrate.
AB  - It was found that EGF decreased both the basal- and the glucagon-stimulated
      gluconeogenesis from lactate alone or from a high lactate/pyruvate ratio and that
      it enhanced both the basal- and the glucagon-inhibited glucose synthesis from
      pyruvate alone or from a low lactate/pyruvate ratio. These findings demonstrate
      that the effect of both EGF and glucagon on glucose production by isolated
      hepatocytes depends on the red-ox state of the substrate.

PMID- 1995080
TI  - Phosphorylase kinase from bovine stomach smooth muscle: a Ca2(+)-dependent
      protein kinase associated with an actin-like molecule.
AB  - Phosphorylase kinase was purified (110-fold) from bovine stomach smooth muscle by
      a procedure involving DEAE-cellulose chromatography, ammonium sulfate
      fractionation and glycerol density ultracentrifugation. On sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) the final enzyme preparation shows
      a single protein band of 43 kDa. The purified protein exhibits a close similarity
      with bovine aortic actin, as revealed by amino acid analysis and sequencing of a
      tryptic decapeptide fragment, although it differs widely from actin in several
      respects. In our effort to separate phosphorylase kinase activity from the 43 kDa
      protein we used a variety of chromatographic procedures, but in all cases the
      catalytic activity (when eluted) was accompanied by the 43 kDa protein band.
      Bovine stomach phosphorylase kinase exhibits an apparent molecular mass of 950
      kDa, it shows a low Vmax value for phosphorylase b (85 nmol.min-1.mg-1), a pH
      6.8/8.2 activity ratio of 0.23, it has an absolute requirement for Ca2+ and it is
      activated 1.8-fold by Ca2+/calmodulin. Furthermore, the protein kinase activity
      is neither inhibited by antibodies against rabbit skeletal muscle phosphorylase
      kinase nor activated by protein phosphorylation. These results suggest that
      bovine stomach phosphorylase kinase is tightly bound to an aggregate of actin
      like molecules.

PMID- 1995082
TI  - Cerebral laterality, symptoms, and diagnosis in psychotic patients.
AB  - A dichotic nonsense test and a dichotic word test were used to assess cerebral
      laterality in 100 acutely symptomatic inpatients. Schizophrenic patients had
      significantly lower right ear advantages (REAs) than healthy controls, depressed
      patients, or schizoaffective patients. Manic patients did not differ from any
      other group, but manics with lower REAs were likely to have more symptoms of
      thought disorder than of mood disturbance while the reverse was likely to be true
      for manic patients with higher REAs. A subset of patients tested after symptom
      remission showed recovery-related increases in REA on the nonsense test and
      decreases on the word test, replicating previous findings. Those schizophrenics
      with evidence of greater disease-related decreases in REA on the nonsense than on
      the word test had predominantly negative symptoms whereas those with similar
      changes on the two tests had predominantly positive symptoms. These observations
      suggest the hypothesis that positive symptoms are related to overactivation of a
      dysfunctional left hemisphere by right hemisphere input while negative symptoms
      reflect a left hemisphere deficit state.

PMID- 1995081
TI  - The effect of transforming growth factor beta on rates of procollagen synthesis
      and degradation in vitro.
AB  - Transforming growth factor beta (TGF beta) is known to stimulate procollagen
      production and steady-state levels of procollagen mRNAs, but its ability to
      affect post-translational processing of procollagen has been little studied. This
      paper demonstrates the application of recently developed ultrasensitive methods
      for measuring hydroxyproline to assess rates of procollagen synthesis and
      degradation in vitro with and without TGF beta. Foetal rat fibroblasts
      synthesized 8.63 +/- 0.21 pmol hydroxyproline/micrograms DNA per h, which
      corresponds to approx. 40 molecules of procollagen/cell per s. Addition of TGF
      beta to cultures increased total amounts of procollagen synthesized and degraded
      by 112% and 82%, respectively, but there was a significant decrease in the
      proportion of procollagen degraded (control, 38.0 +/- 1.1%; TGF beta, 32.3 +/-
      0.9%; P less than 0.005). This study demonstrates a novel mechanism which may
      contribute to the TGF beta-induced increase in procollagen production by
      fibroblasts.

PMID- 1995083
TI  - Morning or evening bright light treatment of winter depression? The significance
      of hypersomnia.
AB  - In a randomized crossover design 19 patients with winter depression were treated
      with 7 days of bright morning light (6:00 to 8:00 AM) and 7 days of evening light
      (7:00 to 9:00 PM). Bright light in the morning reduced the Hamilton Depression
      Rating Scale score from 22.3 to 5.5; bright light in the evening decreased the
      Hamilton score from 21.0 to 12.2. Improvement in the depression as measured by
      the Hamilton Depression Rating scores was greater with morning light compared
      with evening lights. Hypersomnia was associated (p less than 0.05) with a
      superior response to morning light.

PMID- 1995084
TI  - Manic-depressive and pure manic states after brain lesions.
AB  - Although mania is a rare complication of brain lesions, recent reports have
      emphasized the importance of lesion location and genetic predisposition in these
      patients. In the present study we compared patients who developed a bipolar
      affective disorder (i.e., mania and depression) after a brain lesion with
      patients who only developed mania. Although no significant between-group
      differences were found on demographic variables, the manic-depressed group showed
      significantly more impairments on the Mini Mental State Exam than the mania only
      group. All the bipolar patients had subcortical lesions (mainly right head of the
      caudate and right thalamus), while patients with unipolar mania had significantly
      higher frequency of cortical involvement (mainly right orbitofrontal and
      basotemporal cortices). It is suggested that subcortical and cortical right
      hemisphere lesions may produce different neurochemical and/or remote metabolic
      brain changes that may underlie the production of either a bipolar disease or a
      unipolar mania.

PMID- 1995085
TI  - Brain morphology in first-episode schizophrenic-like psychotic patients: a
      quantitative magnetic resonance imaging study.
AB  - Brain morphology was examined using magnetic resonance imaging in 30 first
      episode patients with a schizophreniclike psychosis, 15 chronic schizophrenics,
      and 20 neurological controls. Statistical analyses of computer-generated
      measurements of regions of interest were controlled for gender, age, social
      class, and total brain volume. Lateral ventricular size was increased in both
      first-episode and chronic schizophrenic patients, with greater significance on
      the left than on the right side. Only the chronic patients, however, had reduced
      temporal lobe size, which also was greater on the left side. No major
      correlations of regional brain morphological measurements with cognitive
      functioning were found, although some measurements of verbal memory were
      correlated with parahippocampal size. This is a report of a preliminary study
      that suggests that some morphological brain changes may be present at the time of
      first treatment for a psychotic illness, whereas others may occur later in the
      course of illness. Future prospective studies may determine the clinical
      significance of these changes and whether they progress with the development of
      illness chronicity.

PMID- 1995086
TI  - Inhibition of pyruvate dehydrogenase complex (PDHC) by antipsychotic drugs.
AB  - The effects of 11 antipsychotic drugs on the pyruvate dehydrogenase complex
      (PDHC) prepared from bovine heart and rat brain were investigated. All inhibited
      PDHC to varying extents. With clinically equivalent doses, chlorpromazine and
      thioridazine inhibited the most and fluphenazine and thiothixene the least. The
      relationship of degree of inhibition of PDHC by neuroleptics to clinical
      improvement of 32 outpatients treated with acetazolamide and thiamine (A + T)
      ancillary therapy for chronic mental illness suggests that patients treated with
      psychoactive drugs that inhibit PDHC the least are most likely to have a
      favorable response with A + T treatment.

PMID- 1995087
TI  - Alfred Hoche and DSM-III-R.

PMID- 1995088
TI  - The prognostic significance of HPA-axis disturbance in panic disorder: a three
      year follow-up.
AB  - Seventy-seven patients with DSM-III panic disorder underwent a baseline
      dexamethasone suppression test (DST), participated in an 8-week controlled
      treatment trial, and provided follow-up interviews 2-4 years later. The 20
      patients who had exhibited DST nonsuppression at baseline had more symptoms of
      anxiety, more work and social disability, and a greater likelihood of ongoing
      major depression than did patients who had had normal DST results. DST
      nonsuppression in panic disorder apparently indicates a more persistent and
      chronically disabling condition.

PMID- 1995089
TI  - Hirudin interruption of heparin-resistant arterial thrombus formation in baboons.
AB  - To determine the role of thrombin in high blood flow, platelet-dependent
      thrombotic and hemostatic processes we measured the relative antithrombotic and
      antihemostatic effects in baboons of hirudin, a highly potent and specific
      antithrombin, and compared the effects of heparin, an antithrombin III-dependent
      inhibitor of thrombin. Thrombus formation was determined in vivo using three
      relevant models (homologous endarterectomized aorta, collagen-coated tubing, and
      Dacron vascular graft) by measuring: (1) platelet deposition, using gamma camera
      imaging of 111In-platelets; (2) fibrin deposition, as assessed by the
      incorporation of circulating 125I-fibrinogen; and (3) occlusion. The continuous
      intravenous infusion of 1, 5, and 20 nmol/kg per minute of recombinant hirudin
      (desulfatohirudin) maintained constant plasma levels of 0.16 +/- 0.03, 0.79 +/-
      0.44, and 3.3 +/- 0.77 mumol/mL, respectively. Hirudin interrupted platelet and
      fibrin deposition in a dose-dependent manner that was profound at the highest
      dose for all three thrombogenic surfaces and significant at the lowest dose for
      thrombus formation on endarterectomized aorta. Thrombotic occlusion was prevented
      by all doses studied. In contrast, heparin did not inhibit either platelet or
      fibrin deposition when administered at a dose that maximally prolonged clotting
      times (100 U/kg) (P greater than .1), and only intermediate effects were produced
      at 10-fold that dose (1,000 U/kg). Moreover, heparin did not prevent occlusion of
      the test segments. Hirudin inhibited platelet hemostatic function in concert with
      its antithrombotic effects (bleeding times were prolonged by the intermediate and
      higher doses). By comparison, intravenous heparin failed to affect the bleeding
      time at the 100 U/kg dose (P greater than .5), and only minimally prolonged the
      bleeding time at the 1,000 U/kg dose (P less than .05). We conclude that platelet
      dependent thrombotic and hemostatic processes are thrombin-mediated and that the
      biologic antithrombin hirudin produces a potent, dose-dependent inhibition of
      arterial thrombus formation that greatly exceeds the minimal antithrombotic
      effects produced by heparin.

PMID- 1995090
TI  - Philadelphia chromosome and monosomy 7 in childhood acute lymphoblastic leukemia:
      a Pediatric Oncology Group study.
AB  - During an 8-year period, 3,638 children from institutions of the Pediatric
      Oncology Group (POG) were diagnosed with acute lymphoblastic leukemia (ALL).
      Fifty-seven patients had Philadelphia chromosome-positive (Ph1) ALL. Blast cells
      obtained at diagnosis from 13 of these 57 cases (23%) were also found to have
      partial or complete monosomy 7 (-7). This subgroup of children with Ph1/-7 ALL
      was comprised primarily of older males with early B-lineage ALL. Bone marrow
      specimens from six Ph1/-7 patients were studied further using the polymerase
      chain reaction and primers that flank the ALL, and chronic myelogenous leukemia
      breakpoints to determine the molecular characteristic of the 9;22 translocation.
      Rearrangements were detected in RNA from bone marrow and/or peripheral blood
      cells of six patients, although four were in hematologic remission at the time of
      the analysis. Five cases showed the ALL breakpoint, while one child with Ph1/-7
      showed the chronic myelogenous leukemia breakpoint. The induction failure rate
      was much higher in this subgroup (31%) as compared with Ph1-negative cases, and
      the projected duration of event-free survival reflected the aggressive nature of
      this subgroup because no children are projected to remain in remission at 2
      years. ALL with both the 9;22 translocation and -7 appears to represent a unique
      and previously undescribed subgroup of childhood ALL associated with a
      particularly adverse outcome. Leukemic transformation in such patients may
      involve the interaction of a dominant oncogene (Ph1) and a tumor suppressor gene
      (-7).

PMID- 1995091
TI  - Inhibition of hydroxymethylglutaryl coenzyme A reductase activity induces a
      paradoxical increase in DNA synthesis in myeloid leukemia cells.
AB  - The effects of competitive inhibition of hydroxymethylglutaryl coenzyme A (HMG
      CoA) reductase by compactin on the in vitro proliferation of peripheral blood
      myeloid leukemia cells were studied using the cells from 45 patients with acute
      myeloid leukemia or chronic myelogenous leukemia in blast phase. The cells from
      58% of these patients showed a dose-related inhibition of DNA synthesis when
      incubated with compactin. Unexpectedly, cells from 18% of the patients were
      resistant to the inhibitory effects of compactin on DNA synthesis and responded
      to the HMG CoA reductase inhibition with an actual increase in the incorporation
      of 14C-labeled thymidine into DNA. Another 18% of the patients studied displayed
      both inhibition and stimulation of DNA synthesis in a biphasic response depending
      on the particular concentration of compactin used. The maximum enhanced rates of
      cellular DNA synthesis were observed with lower compactin concentrations (5 x 10(
      7) mol/L) than were required for maximum inhibition of DNA synthesis (10(-5)
      mol/L). Leukemia cells displaying a stimulated response to compactin had a
      significantly lower baseline DNA synthetic rate than did cells that showed an
      inhibitory response of DNA synthesis to compactin. There was no correlation
      between these cells' varying DNA synthetic response to compactin and measures of
      baseline HMG CoA reductase activity or acetate conversion to cholesterol. Whereas
      the observation of cellular DNA synthesis stimulation by HMG CoA reductase
      inhibition has not been observed in other mammalian cells and seems paradoxical,
      explanations may emerge in light of our growing knowledge concerning the
      importance of isoprenylation for the function of certain cell regulatory
      proteins.

PMID- 1995092
TI  - Preliminary studies for an immunotherapeutic approach to the treatment of human
      myeloma using chimeric anti-CD38 antibody.
AB  - Multiple myeloma is a disease in which conventional chemotherapy has only limited
      value, but which may be ideal for treatment with passive antibody against a
      suitable cell surface antigen on the neoplastic plasma cell. The CD38 antigen is
      known to be present on the majority of neoplastic plasma cells, and this was
      confirmed by detailed examination of bone marrow aspirates from three patients.
      Strong expression of CD38 was confined to cells which, by the criteria of light
      scattering profiles and possession of cytoplasmic Ig, were plasma cells. The vast
      majority of neoplastic plasma cells appeared to be involved. Using a cell line as
      a model, it was found that the CD38 antigen acts as a target for a chimeric
      antibody prepared from the antibody OKT10. The chimeric antibody consists of the
      Fab portion of the mouse monoclonal antibody linked by a stable thioether bond to
      an Fc molecule derived from human IgG1, thereby forming mouse Fab-human Fc. In
      contrast to the parent antibody, the chimeric molecule mediates antibody
      dependent cellular cytotoxicity (ADCC) very efficiently with human blood
      mononuclear effector cells, and is effective at low concentration. Also, even
      though the CD38 antigen is present on natural killer cells, there appears to be
      little deleterious action of the antibody on effector cell function. The antibody
      also failed to affect the growth of progenitor cells of the
      granulocyte/macrophage or erythroid lineages present in normal bone marrows,
      despite the suspicion that these cells express the antigen. Other advantages of
      the CD38 molecule are that it is not found in the serum of patients with myeloma,
      and it does not appear to modulate in vitro. Fourteen patients with florid
      myeloma and on various chemotherapeutic regimes had an undiminished capacity to
      mediate ADCC with the chimeric antibody, when compared with normal individuals.
      The maintenance of ADCC activity, coupled with the known suppression of the
      antibody response in these patients, augers well for treatment with chimeric
      antibody.

PMID- 1995093
TI  - NB4, a maturation inducible cell line with t(15;17) marker isolated from a human
      acute promyelocytic leukemia (M3).
AB  - Acute promyelocytic leukemia (APL) is a well-defined entity among acute leukemia,
      cytogenetically characterized by a t(15;17) (q22;q11-12) translocation. In vitro
      and in vivo studies suggest that all-trans retinoic acid (RA) treatment restores
      cell maturation. We have isolated the first permanent cell line with t(15;17),
      derived from the marrow of a patient with APL in relapse. The establishment of
      the cell line, its morphologic, karyotypic, and immunohistochemical features are
      reported. RA induced cell line maturation. Cells strongly expressed myeloid
      markers, but also some T-cell markers. Additional karyotypic abnormalities, a 12p
      rearrangement and the possible presence of a homogeneous staining region (HSR) on
      19q+ are discussed both in relation to T-cell (CD2, CD4) and monocyte (CD9)
      markers, and to the acquired cell growth autonomy. The cell line represents a
      remarkable tool for biomolecular studies.

PMID- 1995094
TI  - Interphase cytogenetic analysis detects minimal residual disease in a case of
      acute lymphoblastic leukemia and resolves the question of origin of relapse after
      allogeneic bone marrow transplantation.
AB  - We used in situ hybridization with a probe for the X chromosome to study
      interphase cells of bone marrow and peripheral blood specimens from a male
      patient with acute lymphoblastic leukemia characterized by hyperdiploidy,
      including trisomy X. In a posttreatment bone marrow specimen, which was
      interpreted as a regenerating bone marrow morphologically and which demonstrated
      a normal karyotype cytogenetically, trisomy X was found in 16 of 1,000 interphase
      cells. This finding indicated the presence of leukemic cells that were undetected
      by conventional morphologic and cytogenetic techniques (ie, minimal residual
      disease). Cytogenetic studies of a relapse specimen obtained after a sex
      mismatched bone marrow transplant showed only a normal female karyotype in each
      of 40 metaphase cells, suggesting that the relapse occurred in donor cells.
      However, interphase analysis demonstrated trisomy X in more than 80% of
      interphase cells and indicated that the relapse was of the original clone and was
      not a transformation of donor cells. This case illustrates that interphase
      analysis can be useful as an adjunct to conventional cytogenetic analysis in the
      detection of minimal residual disease and in the analysis of interphase cells
      that are not accessible to routine cytogenetic methods. It also illustrates that
      previously reported instances of relapse of leukemia in donor cells could have
      been incorrect if supported by cytogenetic data alone.

PMID- 1995095
TI  - Quantitation of immunoglobulin associated with senescent erythrocytes from the
      rabbit.
AB  - The biochemical processes that determine the lifespan of mammalian erythrocytes
      are unknown; one prominent theory suggests that antibody binding to the senescent
      red blood cell identifies it for removal from the circulation. To address this
      question, we have used a newly developed procedure for the isolation of aged
      erythrocytes that involves the biotinylation of rabbit red blood cells, in vivo
      aging of these cells, and the eventual in vitro recovery of the aged red blood
      cells by their affinity for an avidin support. Erythrocytes isolated with this
      method were found to have near-normal levels of cell-associated Ig throughout
      their 60-day lifespan. These data suggest that IgG accumulation is not part of
      the normal senescence process for erythrocytes in rabbits.

PMID- 1995096
TI  - High hemoglobin A2 beta 0-thalassemia due to a 532-basepair deletion of the 5'
      beta-globin gene region.
AB  - We identify and characterize a novel beta 0-thalassemia mutation that is
      associated with an unusually high level of hemoglobin (Hb) A2 in the
      heterozygote. This newly discovered mutation is caused by a 532-basepair deletion
      that extends from positions -454 to + 78 relative to the mRNA cap site of the
      beta-globin gene. The propositi are 9-month-old fraternal twins. One of the twins
      is a compound heterozygote for the deletion and Hb S, the other is a compound
      heterozygote for the deletion and Hb C.

PMID- 1995097
TI  - Preparation and characterization of an intravenous solution of IgG from human
      immunodeficiency virus-seropositive donors.
AB  - An intravenous solution of 99% pure globulin (hyperimmune IgG, HIVIG) was
      obtained from pooled plasma of selected human immunodeficiency virus (HIV-1)
      seropositive asymptomatic donors with greater than 400 CD4+/microliters cells per
      microliter and a high titer of antibody to HIV-1 p24 protein. HIVIG had high
      titers of antibody to p24, glycoprotein 41 (gp41), and gp120, group-specific
      neutralizing activity, and binding to the gp120 hypervariable loop region. It
      inhibited syncytia formation. At low concentration, it enhanced viral production
      of HIV-1 in infected peripheral blood monocytes but was inhibitory at higher
      concentration. HIVIG directed group-specific antibody-dependent cellular
      cytotoxicity against HIV-infected targets. For a period of 6 to 28 months, plasma
      donors kept stable antibody titers and had a 1.0% decrease in CD4+ cells per
      month. One gram per kilogram HIVIG injected in two juvenile chimpanzees was well
      tolerated and did not transmit HIV, as measured by negative cell culture, IgM
      immune response to HIV proteins, and polymerase chain reaction. The mean half
      life of HIV-1 p24 antibody was 15 days. These preliminary data suggest that HIVIG
      is a safe product suitable for clinical trial in HIV-1-infected individuals.

PMID- 1995098
TI  - Presentation of Wiskott Aldrich syndrome as isolated thrombocytopenia.

PMID- 1995099
TI  - Production of tumor necrosis factor-alpha by B-cell chronic lymphocytic leukemia
      and hairy cell leukemia cells: considerations regarding bone remodeling in the
      chronic B-cell leukemias.

PMID- 1995100
TI  - Comparison of the hemostatic effects of fresh whole blood, stored whole blood,
      and components after open heart surgery in children.
AB  - In a double-blind study, we compared the postoperative (post-op) blood loss in
      161 children undergoing open heart surgery with cardiopulmonary bypass whose
      immediate post-op transfusion requirements were met with either very fresh whole
      blood (VFWB), 24- to 48-hour-old whole blood or reconstituted whole blood (packed
      red blood cells, fresh frozen plasma [FFP], and platelets). Assignment to
      treatment groups was not strictly random but dependent, in part, on the ability
      of families to provide directed donors for fresh blood. The three patient groups
      were comparable with respect to patient age, pre-op coagulation profiles
      (bleeding time, prothrombin time, activated partial thromboplastin time, platelet
      count, fibrin split products, fibrinogen, and platelet aggregation tests)
      difficulty of operative procedures and time spent on CPB. Mean 24-hour post-op
      blood loss in milliliters per kilogram was 50.9 +/- 9.3 in the VFWB group, 44.8
      +/- 6.0 in the 24- to 48-hour-old group, and 74.2 +/- 8.9 in the reconstituted
      group (p = .03). When blood loss was compared in the 93 children less than 2
      years of age, mean blood loss was 52.3 +/- 10.8 in the VFWB group, 51.7 +/- 7.4
      in the 24- to 48-hour-old group, and 96.2 +/- 10.7 in the reconstituted group (P
      = .001). For subjects who had received reconstituted blood, 30-minute and 3-hour
      post-op platelet aggregation responses to adenosine diphosphate (10 mumol/L) and
      30-minute aggregation response to epinephrine (2.5 mumol/L) were more depressed
      than in the VFWB and 24- to 48-hour groups (P less than .001, P = .005, and P =
      .02). Comparison of other post-op coagulation tests could not explain the
      increased blood loss in the reconstituted group. We conclude that the transfusion
      of less than 48 hours old whole blood is associated with significantly less post
      op blood loss than the transfusion of packed red blood cells, FFP, and platelets
      in children under 2 years old who underwent complex cardiac surgery. The blood
      losses associated with the transfusion of VFWB and 24- to 48-hour-old blood are
      comparable and may be, in part, due to better functioning platelets.

PMID- 1995101
TI  - Treatment of aplastic anemia in children with recombinant human granulocyte
      colony-stimulating factor.
AB  - Twenty children (aged 1 to 17 years) with severe or moderate aplastic anemia were
      treated with recombinant human granulocyte colony-stimulating factor (rhG-CSF) at
      a dose of 400 micrograms/m2 per day administered as a 30-minute intravenous (IV)
      infusion daily for 2 weeks. This treatment increased the neutrophil counts (2.7-
      to 28.0-fold) in 12 of the 20 patients. Increasing doses (800 or 1,200
      micrograms/m2 per day) were administered to five patients who had not responded
      to the initial dose, and three showed an increase in neutrophil count.
      Differential counts of bone marrow (BM) aspirates showed an increase in the
      myeloid/erythroid ratio. The response was transient, however, and the neutrophil
      count returned to baseline within 2 to 10 days of discontinuing treatment. No
      severe toxicity attributable to rhG-CSF was observed. The results suggest that
      this agent is effective in stimulating granulopoiesis in children with aplastic
      anemia. Our study also indicates that rhG-CSF will be particularly useful in
      managing patients with aplastic anemia complicated by bacterial or fungal
      infection.

PMID- 1995102
TI  - Basic fibroblast growth factor stimulates myelopoiesis in long-term human bone
      marrow cultures.
AB  - We previously showed that basic fibroblast growth factor (bFGF) is a potent
      mitogen for human bone marrow (BM) stromal cells and significantly delays their
      senescence. In the present study, we demonstrated that low concentrations of bFGF
      (0.2 to 2 ng/mL) enhance myelopoiesis in long-term human BM culture. Addition of
      bFGF to long-term BM cultures resulted in an increase in (a) the number of
      nonadherent cells (sixfold), particularly those of the neutrophil granulocyte
      series; (b) the number of nonadherent granulocyte colony-stimulating factor (G
      CSF)- and granulocyte-macrophage colony-stimulating factor (GM-CSF)-responsive
      progenitor cells; (c) the number of adherent foci of hematopoietic cells (10
      fold); and (d) the number of progenitor cells in the adherent stromal cell layer.
      These effects were not noted with higher concentrations of bFGF (20 ng/mL). Thus,
      low concentrations of bFGF effectively augment myelopoiesis in human long-term BM
      cultures, and bFGF may therefore be a regulator of the hematopoietic system in
      vitro and in vivo.

PMID- 1995103
TI  - Synergistic effects of nerve growth factor and granulocyte-macrophage colony
      stimulating factor on human basophilic cell differentiation.
AB  - We have recently shown that nerve growth factor (NGF) promotes human
      granulopoiesis, specifically augmenting basophilic cell differentiation observed
      in methylcellulose hematopoietic colony assays of human peripheral blood. Because
      the NGF effect was seen in the presence of conditioned medium derived from a
      human T-cell line (Mo-CM) containing granulocyte-macrophage colony-stimulating
      factor (GM-CSF), we examined interactions of purified NGF and recombinant human
      GM-CSF (rhGM-CSF) on granulocyte growth and differentiation. rhGM-CSF stimulated
      a dose-dependent increase in methylcellulose colony growth at concentrations
      between 0.1 U/mL and 10 U/mL, and in the presence of NGF at 500 ng/mL this effect
      was enhanced. The number of basophilic cell colony-forming units (CFU-Baso) and
      histamine-positive colonies increased synergistically when NGF was added to rhGM
      CSF. Furthermore, because Mo-CM acts with sodium butyrate to promote basophilic
      differentiation of alkaline-passaged myeloid leukemia cells, HL-60, we also
      examined the interaction of NGF and Mo-CM or rhGM-CSF using this assay. In the
      presence of NGF, Mo-CM at concentrations of 0.5% to 20% vol/vol, and rhGM-CSF at
      concentrations of 0.1 U/mL to 100 U/mL synergistically increased histamine
      production by butyrate-induced, alkaline-passaged HL-60 cells; this was
      associated with the appearance of metachromatic, tryptase-negative, IgE receptor
      positive cells. The effects of rhGM-CSF or Mo-CM were completely abrogated by a
      specific anti-rhGM-CSF neutralizing antibody in methylcellulose, with or without
      NGF; the NGF synergy with rhGM-CSF in the HL-60 assay was also inhibited by
      either anti-rhGM-CSF or anti-NGF antibody. These studies support the notion that
      differentiation in the basophilic lineage may be enhanced by NGF acting to
      increase the number of GM-CSF-responsive basophilic cell progenitors.

PMID- 1995104
TI  - Hospital response to a chemical incident: report on casualties of an
      ethyldichlorosilane spill.

PMID- 1995105
TI  - Mobility aids and appliances for disabled children.

PMID- 1995106
TI  - Accident and emergency services.

PMID- 1995107
TI  - Retinoblastoma linked with Seascale.

PMID- 1995108
TI  - Sexual expression in paraplegia.

PMID- 1995109
TI  - Socioeconomic conditions and ischaemic heart disease.

PMID- 1995110
TI  - Lassa fever.

PMID- 1995111
TI  - Renal artery stenosis.

PMID- 1995112
TI  - First line treatment in hypertension.

PMID- 1995113
TI  - General practice experience of patient recall.

PMID- 1995115
TI  - Major chemical disasters.

PMID- 1995114
TI  - Storage times for Guthrie cards.

PMID- 1995116
TI  - Transient global amnesia.

PMID- 1995117
TI  - "Taken from this place and hanged by the neck...".

PMID- 1995118
TI  - Treating children with spina bifida.

PMID- 1995119
TI  - Magnetic resonance imaging of the head and spine: effective for the clinician or
      the patient?
AB  - OBJECTIVES: To test how the results of magnetic resonance imaging influence
      clinicians' diagnoses and management plans for patients with cranial and spinal
      problems and to assess changes in the quality of life of these patients. DESIGN:
      Survey of patients undergoing cranial and spinal magnetic resonance imaging with
      questionnaires about diagnoses and intended management plans before and after
      imaging and quality of life questionnaires at the time of imaging and again four
      months later. SETTING: Regional magnetic resonance imaging and spectroscopy unit.
      SUBJECTS: 100 consecutive patients referred for cranial imaging in early 1989;
      100 similar patients referred for spinal imaging. MAIN OUTCOME MEASURES: Changes
      in clinicians' leading diagnoses after magnetic resonance imaging and their
      confidence in these diagnoses; changes in intended management plans; assessment
      of the contribution to the future management of the patient; changes in patients'
      quality of life. RESULTS: Magnetic resonance imaging altered the clinicians'
      leading diagnoses in 35 of 169 (21%) cases. The clinicians became more confident
      about their leading diagnoses in 90 of 167 (54%). There was a change in
      management plan in 113 of 182 (62%). The clinicians considered that magnetic
      resonance imaging made an important contribution to management in 119 of 162
      (73%) patients. Overall, the patients' quality of life was unchanged at the four
      month assessment. CONCLUSIONS: Magnetic resonance imaging of patients with
      cranial and spinal problems influences clinicians' diagnoses and management
      plans, but the quality of life of these patients remains unchanged.

PMID- 1995120
TI  - Prevalence of Chlamydia trachomatis infection in women having cervical smear
      tests.
AB  - OBJECTIVE: To determine the prevalence of sexually transmitted diseases in
      patients with normal and abnormal cervical smears. DESIGN: A prospective study of
      asymptomatic women with normal cervical smears attending their general
      practitioner and newly referred patients with abnormal smears attending a
      colposcopy clinic. SETTING: A hospital based colposcopy clinic and an urban
      general practice (list size 5500) in north west Glasgow. SUBJECTS: 197
      asymptomatic women attending their general practitioner for cervical smear tests
      and 101 randomly selected patients attending the colposcopy clinic for
      investigation of abnormal smears. MAIN OUTCOME MEASURES: Presence of various
      sexually transmitted infections as determined by culture and serological tests.
      RESULTS: Of the 101 women with cytological abnormalities, six had current
      chlamydial infection proved by culture and none had gonococcal infection; of the
      197 women with normal smears, 24 (12%) had a chlamydial infection and two had
      gonorrhoea. Serological studies for Chlamydia trachomatis specific antibody also
      indicated that a large proportion of patients had been exposed to this agent in
      both groups. There was no significant difference between the groups in the
      prevalence of any sexually transmitted disease studied. CONCLUSION: A high
      prevalence of chlamydial infection is present in women in north west Glasgow
      irrespective of their cervical cytological state.

PMID- 1995121
TI  - Ventilatory function as a predictor of fatal stroke.
AB  - OBJECTIVE: To investigate the relation between ventilatory function and
      subsequent mortality due to cerebrovascular disease. DESIGN: Prospective
      longitudinal study. SUBJECTS: A total of 18,403 male civil servants aged 40-64
      years at entry examination for the Whitehall study. MAIN OUTCOME MEASURE:
      Mortality from cerebrovascular disease (ICD8 430-438) after 18 years of follow
      up. RESULTS: In all, 262 men with sinus rhythm at entry died due to stroke during
      the 18 years of follow up. Compared with men with a forced expiratory volume in
      one second of greater than or equal to 3.5 litres those with a value of less than
      3.0 litres were almost twice as likely to die of cerebrovascular disease (rate
      ratio adjusted for age and systolic blood pressure = 1.88, 95% confidence
      interval 1.32 to 2.69). This increased risk occurred within each tertile of
      systolic blood pressure. Nested case-control analyses were used to control
      precisely for confounding effects of age, height, and smoking (by matching) and
      employment grade and physiological risk factors (by modelling). The effect of
      forced expiratory volume in one second was independent of age, height, smoking
      habits, employment grade, blood pressure, weight, cholesterol concentration,
      glucose tolerance, electrocardiographic abnormalities, history of chest pain, and
      history of intermittent claudication. CONCLUSIONS: Measurements of ventilatory
      function may assist clinical decisions about whether to treat mild hypertension.
      Impaired ventilatory function and stroke may share common causes.

PMID- 1995122
TI  - Smoking and blood pressure in 15 year olds in Dunedin, New Zealand.

PMID- 1995123
TI  - Serum cholesterol concentration and risk of primary brain tumours.

PMID- 1995124
TI  - Reducing hours of work of preregistration house officers: report on a shift
      system.
AB  - OBJECTIVE: To determine the advantages and disadvantages of a shift system of
      working compared with the conventional on call system for preregistration house
      officers. DESIGN: A shift system of working was employed in the unit from 1
      August 1989 to 31 July 1990. During attachments of three or six months four house
      officers rotated at intervals of one month among three daytime shifts and one
      night shift (Mondays to Fridays only). Weekends (48 hours) were worked on a one
      in three rota by the doctors working a day shift. The views of the house officers
      working this shift system were sought in writing and by direct interview.
      SETTING: Professorial surgical unit, Royal Liverpool Hospital. SUBJECTS: The 14
      house officers who were attached to the unit for three or six months during their
      preregistration year. RESULTS: The shift system was preferred to conventional on
      call without exception. The incidence of chronic tiredness was reduced and formal
      hand-over between shifts resulted in more informed decision making by doctors
      while on call. During annual leave it was sometimes necessary to revert to the
      conventional one in three on call system to ensure that daytime work was
      completed. Other disadvantages were the long weekend shift and an inequitable
      distribution of the night shift. The house officers recommended extending the
      shifts to weekends and working the night shift one week in four. CONCLUSION: A
      shift system of working was effective in reducing chronic tiredness among house
      officers, who found it preferable to conventional on call arrangements. Shift
      working is feasible only if the daytime duties of the doctor working at night can
      be completed by the other doctors on the rota.

PMID- 1995125
TI  - The social fund.

PMID- 1995126
TI  - The NHS observed. General practice: feeling fine, getting better.

PMID- 1995127
TI  - Shy, withdrawn, or autistic?

PMID- 1995128
TI  - Suicide in pregnancy and the puerperium.

PMID- 1995129
TI  - Ovarian hyperstimulation: actual and theoretical risks.

PMID- 1995130
TI  - The NHS prepares for war.

PMID- 1995131
TI  - Surgeons and HIV.

PMID- 1995132
TI  - Suicide during pregnancy and in the first postnatal year.
AB  - OBJECTIVES: To calculate age adjusted mortality ratios for suicide by women in
      the first year after childbirth and during pregnancy, and to identify
      characteristics of postnatal suicide in childbearing women. DESIGN: Retrospective
      study based on population data for England and Wales from 1973 to 1984. SUBJECTS:
      Women aged 15-44 who committed suicide in the year after childbirth or during
      pregnancy. MAIN OUTCOME MEASURES: Observed to expected mortality ratios for the
      total postnatal sample, for five year age groups, for unmarried mothers, and for
      suicide after stillbirth; observed to expected mortality ratios for all suicides
      during pregnancy and for five year age groups; the timing of suicides in relation
      to delivery; and the frequency of the various methods of suicide. RESULTS: The
      standardised mortality ratio for postnatal suicide was calculated to be 0.17-
      that is, the actual total was only one sixth of that expected. The low ratio was
      not found after stillbirth, which was associated with a rate six times that in
      all women after childbirth. The low ratio was less pronounced, but still present,
      in teenage mothers and in unmarried mothers. Women who committed suicide after
      childbirth most often did so in the first month, and there was a tendency to use
      violent methods. The standardised mortality ratio for suicide during pregnancy
      was calculated to be 0.05 of all pregnant women. Teenagers were at substantially
      increased risk. CONCLUSIONS: Women in the first year after childbirth and during
      pregnancy have a low risk of suicide despite their high rate of psychiatric
      morbidity. Underreporting of maternal suicides is unlikely to explain the
      findings, though it may affect their magnitude. Motherhood seems to protect
      against suicide. Concern for dependants may be an important focus for suicide
      prevention in clinical practice.

PMID- 1995133
TI  - Serum sialic acid concentration and cardiovascular mortality.
AB  - OBJECTIVE: To determine whether serum sialic acid concentration may be used to
      predict short and long term cardiovascular mortality. DESIGN: Prospective study
      on all men and women who had their serum sialic acid concentration measured as
      part of a general health survey in 1964 or in 1965. All were followed up for an
      average of 20.5 years. SETTING: Geographical part of the county of Varmland,
      Sweden. SUBJECTS: Residents in the area participating in a health check up in
      1964-5 (27,065 men and 28,037 women), of whom 372 men (169 with incomplete data
      and 203 lost to follow up) and 345 women (143 and 202 respectively) were
      excluded; thus 26,693 men and 27,692 women entered the study. The study sample
      was restricted to subjects aged 40-74 during any of the 20 years' follow up. MAIN
      OUTCOME MEASURES: Serum sialic acid concentration, serum cholesterol
      concentration, diastolic blood pressure, body mass index at the general health
      survey visit; cardiovascular and non-cardiovascular deaths during three periods
      of follow up (0-6 years, 7-13 years, and 14-20 years), according to the Swedish
      mortality register, in subjects aged 45-74. RESULTS: Mean serum sialic acid
      concentration (mg/100 ml) was 68.8 (SD 8.0) for men and 69.2 (8.0) for women; the
      average concentration increasing with age in both sexes. A total of 5639 (21%)
      men and 3307 (12%) women died during the follow up period, in whom death in 3052
      (54%) men and 1368 (41%) women was from cardiovascular causes. During short (0-6
      years), medium (7-13 years), and long (14-20 years) term follow up the relative
      risk of death from cardiovascular disease increased with increasing serum sialic
      acid concentration. The relative risk (95% confidence interval) associated with
      the highest quartile of sialic acid concentration compared with the lowest
      quartile was 2.38 (2.01 to 2.83) in men and 2.62 (1.93 to 3.57) in women. Similar
      results were found for deaths from non-cardiovascular disease with relative risks
      of 1.50 (1.34 to 2.68) in men and 1.89 (1.57 to 2.28) in women, but these
      relative risks were significantly lower than those for deaths from cardiovascular
      disease (p less than 0.001 and p less than 0.005 respectively). In multivariate
      analysis of total mortality and of cardiovascular mortality with sialic acid
      concentration, serum cholesterol concentration, diastolic blood pressure, and
      body mass index as independent variables the impact of sialic acid concentration
      was virtually the same as in univariate analysis. CONCLUSION: Serum sialic acid
      concentration is a strong predictor of cardiovascular mortality. A possible
      explanation of these findings is that the serum sialic acid concentration may
      reflect the existence or the activity of an atherosclerotic process, and this may
      warrant further investigation.

PMID- 1995134
TI  - Unintended pregnancies and the use of contraception: changes from 1984 to 1989.

PMID- 1995136
TI  - Impact of medical audit advisory groups.

PMID- 1995135
TI  - Availability of transplantable organs from brain stem dead donors in intensive
      care units.
AB  - OBJECTIVE: By audit from January to June 1989 to quantify, separately for hearts,
      kidneys, liver, lungs and corneas, the possible increases in transplantable
      organs from brain stem dead potential donors in intensive care units and to
      compare them with the increases achieved in October-November 1989, during
      intense, national publicity about transplantation. DESIGN: Prospective audit of
      all deaths in intensive care units in England from 1 January to 30 June 1989 and
      subsequent case study of the impact of publicity on offers and donations during
      October-November 1989. SETTING: 15 regional and special health authorities in
      England. PATIENTS: 5803 patients dying in intensive care units, of whom 497 were
      confirmed as brain stem dead and had no general medical contraindication to organ
      donation. MAIN OUTCOME MEASURES: Organ specific suitability for transplantation
      (as reported by intensive care units); consent for donation of specific suitable
      organs; and procurement of specific organs reported as suitable for
      transplantation and offered. RESULTS: In the 497 (8.6%) brain stem dead potential
      donors were estimated the organ specific suitability for heart as 63%, kidneys
      95%, liver 70%, lungs 29%, and corneas 91%. Refusal of relatives (30%) accounted
      for major losses of suitable organs of all types. For kidneys the loss was
      equivalent to 44% of brain stem dead actual kidney donors. No discussion of organ
      donation was the second most important reason for missed kidney donors, the loss
      being equivalent to 10% of brain stem dead actual donors. Non-procurement or
      difficulties with allocating organs was the second most notable cause of missed
      suitable liver and lung donors; 29% (55) of the offered total of 189 liver donors
      and 27% (21) of 78 offered suitable lung donors in six months. Non-procurement of
      suitable, offered organs was rare for kidneys and modest, of the order of 13% and
      10% respectively, for heart and corneas. Corneal donation from brain stem dead
      potential donors might be improved nearly as much (that is, a 78% increase in
      brain stem dead actual corneal donors) by specific measures to promote corneal
      donation when other organs are offered as by reducing the overall refusal rate.
      Restricted offers, non-procurement, and no discussion of donation accounted for
      nearly equal numbers of lost donations of hearts (each equivalent to 15% of
      donated hearts). During October-November 1989 when there was intense, positive
      publicity about transplantation the rates of refusal and non-discussion fell
      compared with during January-June (22%, 36/163 v 30%, 138/460; 7%, 33/497 v 2%,
      4/167 respectively). Offers of suitable donors increased significantly (p less
      than 0.02) compared with the first six months of 1989, most notably for heart
      donors (80 v 60.1 expected) and kidney donors (122 v 102.1 expected) but only for
      kidneys was there a noticeable 17% increase in actual donors (118 actual audited
      donors v 100.8 expected donors; p = 0.09). CONCLUSIONS: Four strategies to
      increase the supply of transplantable organs from brain stem dead potential
      donors in intensive care units were identified: (a) reducing refusal of relatives
      (b) avoiding non-procurement of actually suitable organs (by logistical
      initiatives) and deterioration of initially suitable organs (by donor care
      initiatives); (c) converting restricted offers to unrestricted offers; and (d)
      ensuring discussion with families. Early referral to the transplant team or
      coordinator gives time for discussion about donor care and agreement on medical
      suitability for donation of specific organs. Solving some of the logistical
      problems of non-procurement may be a prerequisite for increased offers to be
      translated into increased donations. The impact of publicity therefore needs to
      be measured on offers of suitable donors as well as by actual donations.

PMID- 1995137
TI  - Is housing a public health issue? A survey of directors of public health.
AB  - OBJECTIVE: To determine the views of directors of public health on the importance
      of housing for public health and their departments' and health authorities'
      participation in housing issues. DESIGN: Postal self administered questionnaire
      survey. SETTING: All district health authorities in England and health boards in
      Wales, Scotland, and Northern Ireland. SUBJECTS: All 221 district directors of
      public health in England and chief administrative medical officers in Wales,
      Scotland, and Northern Ireland. MAIN OUTCOME MEASURE: Response to questionnaire
      consisting of fixed and open ended questions on housing issues. RESULTS: The
      response rate was 89% (196/221). Housing was perceived as a major health problem
      by 33% (65/196) of directors. Positive responses were most likely from inner city
      districts. In 47% (93/196) of departments there was a formal time commitment to
      housing issues with a median time of one session/week (range one per month to 10
      per week). The main function was allocation of medical priority for public sector
      rehousing. Overall, 73% (144/196) reported some participation in this process.
      Reported participation in joint care planning and links with non-statutory
      housing organisations were uncommon. 53% (104/196) of directors had included
      housing issues in their annual health report. In 16% (32/196) of districts
      specific services for the homeless had been set up. CONCLUSIONS: Although concern
      about the impact of current housing policy on public health was shown by a
      substantial number of directors, the main activity was still allocation of
      medical priority despite a background of increasing housing need and
      homelessness. The underlying need is for greater advocacy to produce a healthy
      housing policy for all, and the annual public health report could be used to
      promote this objective.

PMID- 1995139
TI  - Private medicine: the NHS's safety valve.

PMID- 1995140
TI  - Dressing aids.

PMID- 1995138
TI  - A medical malaise in hospital.

PMID- 1995141
TI  - Health care insurance in the Soviet Union.

PMID- 1995142
TI  - Educational benefits of audit.

PMID- 1995143
TI  - Milk for babies and children.

PMID- 1995144
TI  - Unexplained haematuria.

PMID- 1995145
TI  - Effect of a general practitioner's consulting style.

PMID- 1995146
TI  - Selling tobacco to children.

PMID- 1995147
TI  - Fertility after treatment for cervical intraepithelial neoplasia.

PMID- 1995148
TI  - Male rape.

PMID- 1995149
TI  - Recording diastolic blood pressure in pregnancy.

PMID- 1995150
TI  - Kwashiorkor.

PMID- 1995151
TI  - Ambulance response times.

PMID- 1995152
TI  - Response of older women to invitations for breast screening.

PMID- 1995153
TI  - Do streptococci cause toxic shock?

PMID- 1995154
TI  - Ear wax removal.

PMID- 1995155
TI  - Pain--struggle--courage.

PMID- 1995156
TI  - Women and AIDS.

PMID- 1995157
TI  - Pre-admission possible.

PMID- 1995158
TI  - Leading the way.

PMID- 1995159
TI  - Winning at losing.

PMID- 1995160
TI  - So much to learn, so little time.

PMID- 1995161
TI  - The Botswana-Brandon link.

PMID- 1995162
TI  - Enough discontent.

PMID- 1995163
TI  - Family systems nursing.

PMID- 1995164
TI  - [Losses associated with AIDS].
AB  - Acquired immunodeficiency syndrome has a considerable effect in many areas:
      individual, social, economic, demographic and cultural. Its emotional impact
      alone is pervasive and characterized by catastrophic losses of health,
      employment, independence and friends or loved ones. This study describes these
      losses.

PMID- 1995165
TI  - [Is there a nurse on the ward?].
AB  - Recognizing that their work doesn't quite conform to the typical profile of
      hospital caregiving, nurses at a maximum security prison hospital in Montreal try
      to define their therapeutic role and how they can continue to evolve
      professionally in such a setting. Three main themes are identified in the
      article: understanding the clientele; developing an appropriate care plan; and
      knowledge of one's own strengths and weaknesses.

PMID- 1995166
TI  - An open letter to Canadian nurses.

PMID- 1995167
TI  - Salvage of branch vessels during bifurcation lesion angioplasty: acute and long
      term follow-up.
AB  - To evaluate angiographic success, frequency of branch vessel loss and salvage,
      and long-term outcome, we studied the early and late outcomes of 56 consecutive
      patients who underwent PTCA of bifurcation lesions, which involved the left
      anterior descending or left circumflex coronary artery, with stenoses greater
      than 70% in both the parent and an involved branch vessel. In 35 patients (63%),
      the PTCA strategy was attempted dilation of both the main vessel and the involved
      branch vessels using predominantly a double-wire, sequential balloon technique;
      in 21 (27%) the PTCA attempt was confined to the main vessel alone. Transient
      angiographic occlusion of the branch vessel occurred in 32% of patients in whom
      dilation of both vessels was attempted, and in 38% in whom the main vessel alone
      was dilated (p = NS); 91% of the occluded branch vessels were the salvaged when
      sequential angioplasty of both vessels had been initially planned, compared to
      only 38% when the initial strategy had been dilation of the main vessel alone (p
      less than .05). Predischarge exercise testing showed residual ischemia in 6% of
      patients who had both vessels successfully dilated, versus 37% in those in whom
      dilatation was confined to the main vessels (p less than .01). Clinical
      restenosis, defined as late (greater than 6 weeks) recurrence of angina or a
      positive exercise test, occurred in 42% of patients who had both vessels
      successfully dilated. Thus although bifurcation lesion angioplasty frequently
      results in transient branch vessel loss, these branches can usually be salvaged
      using a double-wire technique but tend to have a higher late restenosis than
      conventional single vessel PTCA.

PMID- 1995168
TI  - Comparison of exercise performance in left main and three-vessel coronary artery
      disease.
AB  - From a consecutive series of patients who underwent rest and exercise
      radionuclide angiography over several years, we retrospectively identified 34
      patients with left main coronary artery disease and 103 patients with three
      vessel coronary artery disease who did not have significant left main disease.
      The results of gated equilibrium radionuclide angiography were compared in these
      2 groups. Multiple exercise hemodynamic, exercise electrocardiographic, and
      exercise radionuclide angiographic parameters were considered in an attempt to
      separate the 2 groups. The only parameter that was significantly different
      between the 2 groups was exercise heart rate. However, no value of the exercise
      heart rate could meaningfully separate the 2 groups. Despite their known
      difference in prognosis, patients with left main and three-vessel disease had
      very similar exercise performance and could not be distinguished from one another
      by exercise electrocardiography or exercise radionuclide angiography. The
      inability to distinguish these two groups is a clear limitation of noninvasive
      exercise modalities.

PMID- 1995169
TI  - Atrial septal occlusion improves the accuracy of mitral valve area determination
      following percutaneous mitral balloon valvotomy.
AB  - We investigated the impact of the atrial communication on the mitral valve area
      calculation after percutaneous mitral balloon valvotomy in 17 patients (15 women,
      2 men; mean age 56 +/- 4 years). The hemodynamic measurements and mitral valve
      area calculations were performed with and without balloon occlusion of the atrial
      septal puncture site. The mitral valve area determined with balloon occlusion was
      significantly smaller than the mitral valve area determined without occlusion
      (1.6 +/- 0.1 vs. 1.9 +/- 0.1 cm2, P less than 0.01), and was similar to the
      echocardiographically determined valve area (1.6 +/- 0.1 cm2). This decrease in
      the calculated mitral valve area with occlusion was associated with a decrease in
      the measured cardiac output, without a change in the mitral valve gradient or the
      diastolic filling period. Occlusion of the atrial septal puncture site may permit
      more accurate determination of the mitral valve area and thus provide a better
      reference point for future comparison should the question or restenosis arise.

PMID- 1995170
TI  - Coronary angioplasty following cardiac transplantation: a case report and review
      of the literature.
AB  - A 23-year-old man underwent successful percutaneous transluminal coronary
      angioplasty of a severe stenosis of the left anterior descending artery 25 months
      after orthotopic heart transplantation. Four months later restenosis of the same
      lesion was treated by repeat PTCA. Angiography 11 months later showed no
      restenosis. In selected cases, PTCA may be useful in treating allograft coronary
      disease.

PMID- 1995171
TI  - Preservation of regional myocardial function during coronary angioplasty with an
      autoperfusion balloon catheter: a case report.
AB  - Echocardiographic assessment of regional myocardial function was performed during
      standard balloon coronary angioplasty followed by autoperfusion balloon
      angioplasty of a proximal left anterior descending artery stenosis. Septal and
      apical akinesis occurred within 60 seconds of standard balloon inflation, but
      regional function was well preserved during prolonged autoperfusion balloon
      inflation.

PMID- 1995172
TI  - Successful mitral valvuloplasty using the Inoue balloon in a patient with mitral
      stenosis associated with subvalvular fibrosis and reduced left ventricular inflow
      cavity: a case report.
AB  - Percutaneous transvenous mitral valvuloplasty (PTMV) was performed with two
      cylindric pigtail balloon catheters in a 52-year-old woman with symptomatic
      mitral stenosis. The subvalvular apparatus was fibrous with welded chordae and
      the subvalvular left ventricular space was markedly reduced. As a result of this
      distorted anatomy, during the inflations, the two balloons constantly slipped
      back into the left atrium before full inflation was obtained. After the
      procedure, the mitral valve area (MVA), as estimated by echo-doppler (ED),
      increased from 1.00 to 1.34 cm2. After 2 months of mild clinical improvement, the
      patient again became symptomatic and ED examination showed a MVA of 1.25 cm2. A
      second PTMV was performed with an Inoue balloon, the entire procedure taking less
      than 1 hour. A stable position of the Inoue balloon and complete dilatation were
      achieved. ED examination showed a mitral valve area of 2.30 cm2. There was no
      mitral regurgitation nor atrial septal defect. After 3 months, she has only
      N.Y.H.A. class I symptoms and MVA, as estimated by ED, was 2.40 cm2.

PMID- 1995173
TI  - Percutaneous transluminal coronary angioplasty of anomalous right coronary
      artery.
AB  - Coronary angioplasty of tortuous anomalous coronary arteries can be technically
      challenging. We describe a successful percutaneous transluminal coronary
      angioplasty (PTCA) of an anomalous right coronary artery after a failed previous
      attempt. The anatomic limitations of anomalous right coronary arteries and
      technical considerations for PTCA are discussed.

PMID- 1995174
TI  - Rate-related left bundle branch block as a cause of non-ischemic chest pain.
AB  - A case is presented of rate-dependent left bundle branch block associated with
      chest pain in a patient with angiographically normal coronary arteries. Lactate
      extraction showed no evidence of myocardial ischemia. It appears that in this
      case, chest pain was associated with sudden ventricular asynergy rather than
      myocardial ischemia.

PMID- 1995175
TI  - Percutaneous right brachial artery approach with 5F catheters for studying
      coronary artery disease.
AB  - We prospectively studied 60 ischemic patients with 5F catheters (Pigtail and
      Amplatz) using the percutaneous right brachial artery approach (group I), in
      order to compare this technique with two groups of 100 patients each randomly
      studied by the femoral route with either 5F (group II) or 8F (group III)
      catheters (Pigtail and Judkins). The following parameters were analyzed: need to
      change the initially elected catheter diameter or/and artery approach; technical
      difficulty for obtaining LV, LCA, and RCA angiograms; total time of X-ray
      exposure; quality image of LV, LCA, and RCA angiograms; incidence of arterial
      puncture related hematomas or total arterial occlusion; and duration of local
      compression after sheath removal. There were no differences between 5F brachial
      and femoral approaches except for the arterial compression time (p less than
      0.01) and the X-ray exposure time (p = 0.03) which were longer with the brachial
      approach. Whatever the route used, 5F showed a mild increase difficulty (brachial
      p = 0.001; femoral p = 0.01) and a mild decreased quality image for LCA
      (branchial p = 0.006; femoral p less than 0.05). Mild hematomas were more
      frequent with 8F catheters (p less than 0.05). The procedure could be completed
      by the elected first artery and type of catheter (5F or 8F) in 57/60 patients in
      group I, in 95/100 in group II, and in 96/100 in group III (nonsignificant
      differences). Thus, the percutaneous right brachial artery approach using 5F
      catheters is similar to the femoral artery approach with the same catheters.
      Although both of them showed a mild increased technical difficulty and a mild
      decreased quality image compared to 8F, mainly for LCA angiograms, they allowed
      complete and reliable angiograms reading and analysis.

PMID- 1995176
TI  - Accuracy and reproducibility of quantitative coronary arteriography using 6 and 8
      French catheters with cine angiographic acquisition.
AB  - To determine the suitability of 6 French catheters for quantitative coronary
      arteriography, the relative accuracy and reproducibility of one type of these
      catheters was compared to that obtained with standard 8 French catheters in 20
      stenoses. Duplicate injections with polyurethane 6 French catheters were obtained
      using hand and power injection technique with cineangiographic acquisition (four
      6 French catheter injections total per stenosis). Measurements of both percent
      diameter stenosis and absolute dimensions were compared to those obtained with
      hand injection and cine acquisition using 8 French catheters as a "gold
      standard." While the reproducibility of dimension determination with the 6 French
      catheter was generally similar to that obtained with the 8 French catheter (0.27
      +/- 0.23 mm for absolute diameter and 8.1 +/- 7.4% for percent diameter
      stenosis), accuracy was significantly less for the 6 French catheter for
      measurement of absolute dimensions. Thus, while apparently well suited for serial
      measurements of the same stenoses, 6 French catheters may not be as accurate in
      the determination of absolute artery dimensions as 8 French catheters.

PMID- 1995177
TI  - Coronary balloon angioplasty through diagnostic 6 French catheters.
AB  - We investigated the use of ultralow profile balloon catheters (Scimed ACE, USCI
      Probe, Cordis, Orion) for coronary angioplasty through 6 French diagnostic
      catheters (Schneider, Cordis). Contrast injection was assisted with a Hercules
      pump (Cordis) in all cases. During 21 procedures, angioplasty of 27 lesions in 20
      selected patients was attempted (1.3 lesion/procedure). Twelve lesions were in
      the right, 10 in the left anterior descending, and 5 in the left circumflex
      coronary artery. Balloon size varied between 2.5 and 3.5 mm. Twenty lesions could
      be successfully dilated (74%) through the 6 French catheter and 7 lesions
      required an exchange to a 7 French angioplasty guiding catheter. For 5 cases,
      another balloon was also necessary to complete the procedure. The final overall
      success rate was 100% per patient and per lesion and there were no major
      complications. Despite the small internal catheter lumen (1.22 mm) coronary
      visualization was adequate, and mechanical support was good. Failures of 6 French
      catheters were attributed to insufficient torque control and excessive friction
      when the balloon crossed the tapered end of the diagnostic catheter. Coronary
      angioplasty through a diagnostic 6 French catheter is feasible and may represent
      a reasonable alternative for simple cases that are done during the same session
      as the diagnostic angiography. Once available, 6 French high flow angioplasty
      guiding catheters without a tapered tip should improve success while retaining
      the advantage of a small femoral puncture site.

PMID- 1995178
TI  - Preliminary experience with 5 and 6 French diagnostic catheters as guiding
      catheters for coronary angioplasty.
AB  - With the reduction in profile of balloon dilation catheters, until recently, it
      has been the internal dimensions and performance of the guiding catheter that has
      mandated the use of 7, 8 or 9 French (F) systems for the performance of
      percutaneous transluminal coronary angioplasty (PTCA). A new 5F catheter design
      (Sherwood Medical Co., St. Louis, MO) provided a large inner lumen (0.4")
      permitting use of 0.20-0.22" fixed-wire PTCA balloon catheters with good coronary
      visualization. Potential advantages include reduced coronary artery ostial trauma
      and catheter induced damping and enhanced patient comfort. We report our initial
      experience in 14 patients undergoing PTCA with a 5 and 6F guide/fixed-wire
      system. Mean age was 63 +/- 10 (43-78 years). PTCA indications: Cardiogenic shock
      (1), post-myocardial infarction angina pectoris (2), grade III angina (5) and
      unstable angina pectoris (6). Vessel attempted: Left anterior descending (3),
      circumflex (4), obtuse marginal (2), diagonal (1), right coronary artery (3), and
      internal thoracic artery (1). Twelve patients had femoral approach; two brachial
      approach. The USCI Probe (USCI Division, Billerica, MA) was used in 8 lesions and
      SCIMED ACE (SCIMED Life Systems, Maplegrove, MN) catheter in 7 lesions.
      Successful 5 or 6F guide/fixed-wire dilations reduced the stenosis (77 +/- 14 to
      37 +/- 30%) and were successfully performed in 79% (11/14). One 5F patient
      required 8F guiding catheter and was dilated with 2.0 fixed-wire balloon. A
      second failed 5F PTCA could not be dilated with any larger conventional system. A
      third total occlusion could not be crossed with a guidewire or fixed wire
      balloon. No patient had a complication.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1995179
TI  - Anatomic and machine projection angles of various radiographic imaging systems
      used for cardiac angiography.
AB  - Quantitation of coronary artery dimensions in serial angiographic studies
      requires an awareness of the variety, complexity, and implications of
      radiographic imaging equipment used for coronary arteriography. Recognition of
      the geometric complexities inherent in angiographic imaging systems is important
      in understanding complex image rotations and ensuring identity of projections
      when serial comparison is desired. Tables, figures, and formulae are provided to
      permit translation of machine angles into patient reference angles and vice
      versa.

PMID- 1995180
TI  - Application of coronary angioplasty to the septal perforator arteries.
AB  - Significant coronary artery disease affecting the septal perforator arteries can
      cause anginal pain, rhythm disturbances, or septal infarction. However, since
      these vessels are usually inaccessible to coronary bypass surgery, there is a
      tendency among angiographers and angioplasters to overlook lesions of the septal
      perforator arteries. Our experience suggests that if medical treatment is not
      sufficient to treat clinical manifestations resulting from septal perforator
      disease, then coronary angioplasty can be considered a therapeutic alternative
      for revascularization. We herein present 11 patients who underwent coronary
      angioplasty of a major septal artery and discuss angiographic and technical
      aspects of the procedure.

PMID- 1995181
TI  - Soft tissue tumours: the genetic basis of development.

PMID- 1995182
TI  - Metabolism of benzo[a]pyrene and (-)-trans-benzo[a]pyrene-7,8-dihydrodiol by
      freshly isolated hepatocytes from mirror carp.
AB  - The metabolism of benzo[a]pyrene (B[a]P) and (-)-trans-benzo[a]pyrene-7,8
      dihydrodiol [(-)-B[a]P-7,8-diol], a major putative proximate carcinogenic
      metabolite of B[a]P, was compared in freshly isolated hepatocytes from mirror
      carp, a strain of common carp (Cyprinus carpio, L.). Hepatocytes incubated with
      40 microM [3H]B[a]P produced 1.22 nmol equivalents of B[a]P metabolites/mg dry wt
      of cells/h. Conjugated derivatives represented approximately 65% of all B[a]P
      metabolites and included glucuronides (38%), glutathione conjugates (21%) and
      sulfates (6%). About 14% of the total accumulated metabolites of B[a]P determined
      after 1 h incubations were identified as unconjugated derivatives, predominantly
      B[a]P-9,10-dihydrodiol and B[a]P-7,8-diol (7.4 and 3.1% of total metabolites
      respectively), with only traces of B[a]P tetrols (less than 1%). Hepatocytes
      incubated with 40 microM (-)-[14C]B[a]P-7,8-diol produced 4.78 nmol equivalents
      of metabolites/mg dry wt during a 1 h incubation, yielding an average rate of
      metabolism during this time period approximately 53% of that determined after a 5
      min incubation. The profile of (-)-B[a]P-7,8-diol metabolites remained constant
      with incubation time (glucuronides, 30-33%; conjugates with glutathione, 43-46%;
      polyhydroxylated B[a]P derivatives plus sulfate conjugates, 22-24%). HPLC
      analysis revealed that polyhydroxylated metabolites amounted to 18% of the total
      metabolites; thus sulfate conjugates amounted to only 4% of the total
      metabolites. The trans-2 B[a]P-tetrol, which is the major hydrolysis product of
      (+)-anti-benzo[a]pyrene-7,8-diol-9,10-epoxide (anti-BPDE), represented
      approximately 11% of the accumulated metabolites of (-)-B[a]P-7,8-diol. Despite
      the much larger amounts of BPDE formed from (-)-B[a]P-7,8-diol than from B[a]P,
      the amounts of B[a]P equivalents covalently bound to cellular DNA were the same
      following 1 h incubations with either substrate (247 +/- 42 or 212 +/- 42 pmol/mg
      DNA respectively). Thus biochemical and physiological factors other than the
      production of BPDE are critically involved in determining the level of DNA
      adducts in hepatocytes as well as the role of these adducts in
      hepatocarcinogenesis.

PMID- 1995183
TI  - Enhancement of N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine-induced tumorigenesis
      in Sprague-Dawley rats by orotic acid.
AB  - The effect of orotic acid (OA) on the carcinogenicity of N-nitroso(2
      hydroxypropyl)(2-oxopropyl)amine (HPOP) in rats was evaluated. A group of 5 week
      old Sprague-Dawley male rats were placed on a synthetic 20% protein diet
      containing 1% OA. A second group was placed on a regular, OA-free diet of similar
      composition. Approximately 2 weeks later, animals from both groups grown to 100 g
      were treated with 400 mg/kg HPOP delivered continuously for 14 days via 2002
      Alzet osmotic pumps implanted s.c. Rats fed the OA diet were kept under this diet
      for 13 weeks following initiation of HPOP treatment and subsequently were placed
      on the regular diet for another 12 weeks, at which time they were killed. In the
      absence of OA, HPOP-treated rats developed adenomas in the kidney and lungs at
      incidences of 5 and 33% respectively, while pancreas and liver were unaffected.
      On the other hand, rats fed the OA diet and treated with HPOP developed renal
      mesenchymal tumors and pulmonary adenomas at incidences of 70 and 65%
      respectively. In addition, HPOP induced cystic lesions in the pancreas of animals
      fed the OA diet. The enhancement of the tumorigenic effectiveness of HPOP was at
      least partly ascribed to the effect of OA treatment on the rate by which
      carcinogen-induced alkylation of DNA was repaired in various tissues.
      Accumulation of N7-methylguanine in kidney, lung and pancreas of rats fed the OA
      diet was 1.6, 1.9 and 2.4 times higher than in respective organs of animals fed
      the regular diet. Similarly, concentrations of the premutagenic O6-methylguanine
      (O6-MeG) were 3.0, 3.1 and 2 times greater in the kidney, lung and pancreas of
      rats fed the OA diet than in the respective organs of those fed the regular diet.
      Feeding an OA diet to HPOP-treated rats did not have an effect on either the
      resistance of the liver to this carcinogen or on the level of O6-MeG accumulation
      in the DNA of this tissue.

PMID- 1995185
TI  - Identification and quantitative distribution of eight analogues of naturally
      occurring fecapentaenes in human feces by high-performance liquid chromatography.
AB  - Fecapentaenes, highly potent fecal mutagens originating from intestinal bacterial
      production, have been suggested to play an essential role in the initiation of
      colorectal cancer. Reviewing the data on fecapentaene occurrence in man, the
      applied methodologies for fecapentaene extraction and analysis appear to be very
      inconsistent. Therefore, we compared several methods and developed an optimal
      extraction and purification procedure for fecapentaene quantification in human
      feces. This method is based upon a dichloromethane extraction of freeze-dried
      material with application of a Potter homogenization instrument and subsequent
      HPLC analysis in combination with photodiode array detection. This system enables
      us to detect and quantify at least eight forms of fecapentaene-like substances
      generally occurring in human stool. We suggest that these peaks represent
      fecapentaene-12 (FP-12) and fecapentaene-14, both with a geometric isomer, as
      well as fecapentaene analogues that have never been reported before. Applying
      this methodology on feces of a group of young healthy persons, we were able to
      detect fecapentaene levels ranging from less than 5 micrograms to 6 mg/kg feces,
      and in 40% of the samples greater than 1.0 mg/kg feces. The newly identified
      fecapentaenes represent 21.7% of total fecapentaene concentration. It appears
      that some fecapentaenes are excreted in higher amounts by females as compared to
      males. Furthermore, we found that fecal mutagenicity to Salmonella tester strain
      TA100 appeared lower than hypothesized on the basis of overall fecapentaene
      contents, and that fecal extracts diminish the mutagenic effect of synthetic FP
      12 dramatically. Apparently, optimal conditions for fecapentaene extraction
      result also in an increased level of co-extracted anti-mutagenic substances.
      Determination of fecal mutagenicity as an index for fecapentaene excretion or
      colorectal cancer risk is therefore not suitable. In order to assess the
      relevance of fecapentaenes in the etiology of colorectal cancer, we suggest that
      a distinction should be made between relative occurrence and degree of genotoxic
      effect in situ of the various fecapentaene analogues.

PMID- 1995184
TI  - Levels of nitrite, nitrate, N-nitroso compounds, ascorbic acid and total bile
      acids in gastric juice of patients with and without precancerous conditions of
      the stomach.
AB  - To determine the relevance of gastric juice factors to gastric carcinogenesis, 56
      patients with unoperated stomachs undergoing endoscopy for dyspepsia had gastric
      juice aspirated and analysed for pH, ascorbic acid, total bile acids, nitrite,
      nitrate and total nitroso compounds (NOCs). Plasma was obtained for vitamin C
      estimation. Antral and body biopsies were assessed for gastritis, Helicobacter
      pylori, atrophy and intestinal metaplasia (IM). Patients with chronic atrophic
      gastritis (n = 17) had lower gastric juice ascorbic acid concentrations (P less
      than 0.001), higher pH (P less than 0.05) and higher incidence of H. pylori
      infection (P less than 0.001) than normal subjects (n = 12). Patients with reflux
      gastritis (n = 9) had higher total bile acids (P less than 0.01). Patients with
      chronic gastritis and IM (n = 11) had higher gastric juice pH (P less than 0.01)
      and total bile acid concentrations (P less than 0.05), and lower gastric ascorbic
      acid concentrations (P less than 0.01) than those with chronic gastritis and no
      IM (n = 24). In chronic gastritis, high nitrite concentrations were associated
      with high pH (P less than 0.01). However, there were no significant differences
      in plasma vitamin C or gastric nitrite, nitrate or total NOC concentrations in
      relation to gastric histology. We conclude that the premalignant condition IM is
      associated with H. pylori infection, low gastric ascorbic acid levels and
      elevated total bile acids, but not to elevation in nitrite or total NOCs in
      fasting gastric juice.

PMID- 1995187
TI  - The correlation of body growth with diethylnitrosamine-induced
      hepatocarcinogenesis in relation to serum insulin and somatomedin-C.
AB  - Caloric restriction depresses the development of several types of tumours, yet
      the mechanisms involved are poorly understood. In the present experiment we
      investigated the development of diethylnitrosamine (DEN)-induced liver tumours in
      mice treated with caffeine. The latter was found to reduce body growth, possibly
      due to increased energy expenditure, without reducing food consumption. Newborn
      mice received an i.p. injection of DEN. At weaning they were either fed lab chow
      ad libitum, with the same diet containing 0.2% (w/w) of caffeine, or their access
      to food was restricted to 70% of that consumed by the ad libitum group. Diet
      caloric restriction starting at weaning in male Swiss mice decreased the rate of
      development of glucose-6-phosphatase-deficient (G6Pd) preneoplastic foci. At the
      age of 24 weeks, 10% of the surface of a standardized liver section of ad libitum
      fed mice was G6Pase negative, compared to only 1% in the restricted mice due to a
      reduction of the number and size of these preneoplastic foci. The number and size
      of G6Pd foci decreased to the same extent with the ingestion of a lab chow
      supplemented with 0.2% of caffeine as with the diet restriction. This finding
      suggests that restriction slows down hepatic tumour growth by modifying body
      growth rather than by limited nutrient supply. In parallel, somatomedin-C (Sm-C)
      and insulin secretion following glucose challenge were decreased in diet
      restricted mice and those treated with 0.2% caffeine. The serum Sm-C and insulin
      levels were respectively 480 and 4.6 ng/ml in the restricted mice, 519 and 16.6
      ng/ml in the caffeine-fed mice and 664 and 25.7 ng/ml in the ad libitum fed mice.
      Our results suggest that the decrease of secretion of these two hormones that are
      known mitogens for hepatocytes in vitro may be responsible at least in part for
      the reduction in the growth of liver tumours.

PMID- 1995186
TI  - The peptide pyroGlu-Gln-Gly-Ser-Asn, isolated from mouse liver, inhibits growth
      of rat hepatoma cells in vitro.
AB  - The peptide pyroGlu-Gln-Gly-Ser-Asn, recently isolated from mouse liver,
      inhibited DNA synthesis and proliferation in vitro of MH1C1 cells, a rat clonal
      strain derived from a Morris transplantable hepatoma. Both the biological peptide
      isolated from mouse liver and the synthetic homolog showed bell-shaped dose
      response curves. Maximal inhibition (approximately 50%) was observed at two
      separate dose ranges: one at 10(-7)-10(-10) M, and one at 10(-14)-10(-15) M.

PMID- 1995188
TI  - Genotoxicity of fluoroquinolines and methylquinolines.
AB  - Quinoline in the presence of microsomal activation exhibits mutagenic activity in
      Salmonella typhimurium TA100 and induces unscheduled DNA synthesis (UDS) in rat
      hepatocytes. Structure-activity studies were performed to determine those
      positions on quinoline critically associated with its genotoxicity. In assays
      performed to determine the ability of 2-, 4-, 6- and 8-methylquinoline to induce
      UDS, only 4- and 8-methylquinoline produced a positive response. This represents
      an improved correlation for these methylquinolines with tumorigenic activity as
      compared to that previously observed with mutagenic activity in S. typhimurium
      TA100. The complete isomeric series of fluoroquinolines were evaluated as
      mutagens in S. typhimurium TA100 and for their potential to induce UDS in rat
      hepatocytes. The only isomers that did not exhibit significant mutagenic activity
      were 2- and 3-fluoroquinoline. Among these isomeric fluoroquinolines 5-, 6-, 7-
      and 8-fluoroquinoline are capable of inducing UDS. No significant effect on UDS
      was observed for 2-, 3- or 4-fluoroquinoline. These data indicate that positions
      1-3 in quinoline are critical sites associated with its genotoxicity.

PMID- 1995189
TI  - Mutational specificities of environmental carcinogens in the lacI gene of
      Escherichia coli: IV. The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3
      pyridyl)-1-butanone.
AB  - We have determined the mutational specificity of the tobacco-specific carcinogen
      4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) by the characterization of
      58 induced Escherichia coli lacI-d mutants at the DNA sequence level. Metabolic
      activation of NNK was carried out using the S9 fraction from Aroclor 1254-treated
      rats. G:C----A:T transitions dominated the spectrum, accounting for 55% of the
      mutations recovered. The other base substitutions recovered include three A:T---
      G:C transitions as well as two A:T----T:A, three A:T----C:G, five G:C----C:G and
      five G:C----T:A transversions. Other classes of mutational events included two
      deletions, three duplications and three frame-shifts. The complexity of the NNK
      mutational spectrum appears consistent with a model that this compound induces
      mutations by both the methylation and the pyridoloxobutylation of DNA.

PMID- 1995191
TI  - N-nitroso compounds in cigarette tobacco and their occurrence in mainstream
      tobacco smoke.
AB  - The tobacco and mainstream smoke of 20 commercial brands of filter and non-filter
      cigarettes were analysed for N-nitroso compounds. The concentrations of N
      nitrosodimethylamine (NDMA), N-nitrosoethylmethylamine (NEMA) and N
      nitrosopyrrolidine (NPYR) in cigarette tobacco were very much lower than in
      mainstream smoke, where the levels were 6.3-76.4 ng/cig NDMA, less than 1.0-7.1
      ng/cig NEMA and 3.9-41.2 ng/cig NPYR. N-Nitrosodiethylamine was not detected in
      mainstream smoke and N-nitrosopiperidine (less than 1.0 ng/cig) was detected in
      the smoke of four unfiltered cigarette brands. The five major non-volatile
      nitrosamines present in cigarette tobacco were 4-(N-nitroso-N-methylamino)butyric
      acid (not detected to 200 ng/cig), N-nitrosopipecolic acid (not detected to 670
      ng/cig), N-nitrososarcosine (22-460 ng/cig), 3-(N-nitroso-N-methylamino)propionic
      acid (110-4990 ng/cig) and N-nitrosoproline (580-15000 ng/cig). The tobacco
      specific nitrosamines N-nitrosoanabasine and N-nitrosoanatabine were found at
      levels of 270-2330 ng/cig and 18-205 ng/cig in cigarette tobacco and mainstream
      smoke respectively. N-Nitrosonornicotine was present at 400-5340 ng/cig and 19
      855 ng/cig in cigarette tobacco and mainstream smoke respectively. 4-(N
      Nitrosomethyl-amino)-1-(3-pyridyl)-1-butanone concentrations of 100-960 ng/cig
      and 21-470 ng/cig in cigarette tobacco and mainstream smoke were determined. 4-(N
      Nitrosomethyl-amino)-4-(3-pyridyl)-1-butanol (iso-NNAL) was detected in four dark
      (French) tobacco unfiltered cigarettes at a concentration range of 140-240 ng/cig
      and 5-11 ng/cig in the corresponding mainstream smoke. For non-filter cigarettes,
      a transfer rate of 3.4-4.6% for iso-NNAL was calculated.

PMID- 1995190
TI  - Modulation of glutathione content and the effect on methionine auxotrophy and
      cellular distribution of homocysteine and cysteine in mouse cell lines.
AB  - The inability of cells in culture to grow in medium where methionine is replaced
      by its metabolic precursor, homocysteine, has been linked to neoplastic
      transformation and termed 'methionine dependence' or 'methionine auxotrophy'. The
      present investigation was undertaken to establish the influence of intracellular
      glutathione level on methionine auxotrophy in different mouse cell lines. A non
      transformed, methionine-independent fibroblast cell line with essential normal
      growth rate in methionine-deficient, homocysteine-supplemented medium (Met-Hcy+),
      showed only a slight initial lag and then the same growth as control when
      glutathione was reduced to less than 5% by the glutathione synthesis inhibitor
      buthionine sulfoximine (BSO). Increasing cellular glutathione by cystamine in a
      completely methionine-dependent leukemia cell line did not stimulate the cells to
      proliferate in Met-Hcy+ medium. A partly methionine-dependent transformed
      fibroblast cell line with reduced capacity to proliferate in Met-Hcy+ medium
      showed increased growth potential when the cells were depleted of glutathione by
      a non-toxic concentration of BSO. An even higher growth potential of these cells
      in Met-Hcy+ medium was obtained by addition of a non-toxic concentration of
      cystamine, while only a transient increase of glutathione content was observed
      under these conditions. Both BSO and cystamine increased the fraction of protein
      bound cysteine and homocysteine in the partly methionine-dependent cells. These
      metabolic alterations correlated with the increased ability of these cells to
      utilize homocysteine for growth. Our results suggest that methionine auxotrophy
      is a metabolic defect that is not related to the cellular glutathione status, but
      may be related to the intracellular distribution between free and protein-bound
      forms of other thiols as cysteine and homocysteine.

PMID- 1995192
TI  - Environmental mutagens that induce the adaptive response to alkylating agents in
      Escherichia coli.
AB  - Many microorganisms exhibit an adaptive response to mutagenic alkylation damage.
      In Escherichia coli the response is regulated by the inducible Ada protein. A
      sensitive immunoassay employing two anti-Ada monoclonal antibodies has been
      developed here to monitor low levels of induction of the Ada protein. This
      protein was detected in non-induced E. coli which contained an average of two
      molecules of Ada per cell. The occurrence of the adaptive response in bacteria
      signals the existence of an ecological niche in which cells are exposed to direct
      acting methylating compounds, but the structure and identity of these agents are
      unknown. Using the immunoassay to search for possible candidates, a number of
      methylating agents and precursors of such agents have been investigated. Carbamyl
      phosphate and methylamine yield N-methylurea, which reacts subsequently with
      nitrite to generate the strong inducer N-methyl-N-nitrosourea. The antibiotic
      streptozotocin also is a potent inducer of the adaptive response. Moreover, the
      abundant environmental mutagen methyl chloride acts as an inducer.

PMID- 1995193
TI  - Complexing of actin and other nuclear proteins to DNA by cis
      diamminedichloroplatinum(II) and chromium compounds.
AB  - Actin was found to be the major protein crosslinked to the DNA of intact Chinese
      hamster ovary cells that were treated with either potassium chromate (hexavalent)
      or cis-diamminedichloroplatinum(II) (cis-platinum). This protein was identified
      as actin by its mol. wt (45 kd), its isoelectric point (pI = 5.4), positive
      reactivity with an actin antibody, and by protease mapping. Additionally, a
      purified actin standard migrated to the same location in a two-dimensional gel
      system as p45. Actin comprised approximately 20% of the protein component in
      chromate-induced DNA-protein crosslinks. In addition, to actin, several other
      major proteins (e.g. 53 kd, pI = 5.2, 50 kd, pI = 9) were crosslinked to DNA
      following exposure to cis-platinum or chromate. These proteins were abundant in
      the nuclear matrix fraction. Hexavalent chromate is the toxicologically active
      form because it is readily taken up into cells by an anion transport system. In
      contrast, trivalent chromium is considerably less toxic because it cannot enter
      the cell; however, most of the hexavalent form is eventually reduced to the
      trivalent form inside the cell. Previous studies have suggested that the
      trivalent form of chromium participates in complexing DNA with proteins. DNA
      protein crosslinks were formed in isolated nuclei or in mixtures of purified DNA
      and protein incubated with trivalent chromium. However, the formation of these
      complexes required at least 16 h of incubation to exchange the parent compound
      ligands. Hexavalent chromate did not form these complexes in vitro under similar
      conditions. Incubation of trivalent chromium with purified actin and DNA resulted
      in DNA-actin crosslinks as detected by an electrophoretic mobility different from
      that of either free actin or DNA when the complex was transferred from a gel to
      nitrocellulose and stained for protein. These studies describe a new technique
      for detecting DNA-protein complexes and demonstrate that actin-DNA structures in
      intact cells create sites that selectively react with metal DNA-protein
      crosslinking agents.

PMID- 1995194
TI  - Magnetic resonance imaging compared with hormonal effects and histopathology of
      estrogen-induced pituitary lesions in the rat.
AB  - Estrogen-induced pituitary lesions in rats were studied in time-sequence
      experiments using magnetic resonance imaging (MRI), hormone determinations and
      light microscopy. The main purpose of the study was to evaluate the usefulness of
      MRI in comparison with conventional biochemical and histopathological methods for
      detecting the pituitary lesions as early as possible and to follow their
      development. Measurements were made at 15 time points, ranging from 1 h to 272
      days after s.c. implantation of the estrogen pellet. High-resolution T1 weighted
      sagittal images with 2 mm slice thickness were made with a 2 Tesla 30 cm small
      bore MRI system. Radioimmunoassay (RIA) was used to determine the different
      pituitary hormones. Conventional histopathology and immunoperoxidase staining
      methods were used to characterize the pituitary lesions and visualize the hormone
      producing pituitary cells respectively. The first histopathological pituitary
      changes (enlarged acidophilic cells with increased number of vacuoles) were seen
      at day 2 after initiation of the estrogen treatment, while at day 4 the first
      immunohistochemical changes (increased number of prolactin-positive cells) were
      encountered. Significantly increased prolactin levels in blood plasma occurred
      from day 9 onwards. Also at day 9, changes of the pituitary gland were first
      visible on MR images, showing rounding of the anterior edge of the gland. Gradual
      enlargement of the pituitary caused by hyperplasia of hypertrophic prolactin
      positive cells could be followed by MRI, and later on pituitary tumors were
      recognized, their images being heterogeneous due to great differences in signal
      intensity ranging from hypo- or iso- to hyperintense. Signal intensities of
      hemorrhagic tumor areas varies widely due to variation in the blood flow
      maintained in these areas. In was concluded that MRI is a powerful tool for
      detecting enlargement and tumors of the pituitary gland in rats. This method
      allows the development of such lesions to be followed in one and the same animal,
      thereby reducing the need of interim kills and thus the number of animals to be
      used.

PMID- 1995195
TI  - Role of ras protooncogene activation in the formation of spontaneous and
      nitrosamine-induced lung tumors in the resistant C3H mouse.
AB  - The role of ras activation in the formation of spontaneous and chemically induced
      tumors was evaluated in the C3H mouse, a strain that has a low incidence of
      spontaneous lung tumors. Lung tumors were induced in C3H mice by treatment with 4
      (N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK), 50 mg/kg, or
      nitrosodimethylamine (NDMA), 3 mg/kg for 7 weeks (3 times/week, i.p.). Eleven
      tumors from each treatment group were evaluated for activated ras genes by direct
      sequencing and oligonucleotide hybridization to slot blots of amplified DNA from
      these tumors. An activated K-ras gene was detected in 100% of NDMA- and NNK
      induced lung tumors, and the activating mutation detected in all samples was a GC
      to AT transition (GGT to GAT) in codon 12. In contrast, only 40% of the seven
      spontaneous lung tumors analyzed contained an activated K-ras gene and the
      mutations identified were not localized to either a specific base or codon. Both
      NNK and NDMA can be activated via alpha-hydroxylation to methylating agents. The
      GC to AT mutation observed in codon 12 in the nitrosamine-induced tumors is
      consistent with the formation of an O6-methylguanine (O6MG) adduct. Similar
      concentrations (13-15 pmoles/mumol deoxyguanosine) of this promutagenic adduct
      were detected in lungs during treatment with either NNK or NDMA. Thus, both these
      nitrosamines appear to activate the K-ras gene in lung through a direct genotoxic
      mechanism involving the formation of the O6MG adduct. The frequency of K-ras
      activation was similar in chemically induced lung tumors from the sensitive A/J
      strain and the C3H mouse, indicating that susceptibility for neoplasia in these
      stains is not related to the ability to activate this gene. Although tumors were
      induced in lung from 100% of C3H mice following chronic carcinogen exposure, both
      the size and the multiplicity was significantly less, while latency was longer
      than that observed in the A/J mouse. These differences could not be attributed to
      an altered propensity for DNA damage, but rather suggest that genetic loci which
      regulate clonal expansion and growth of initiated cells play a major role in the
      susceptibility of pulmonary neoplasia.

PMID- 1995196
TI  - Immunochemical detection of rodent hepatic and urinary metabolites of cooking
      induced food mutagens.
AB  - Monoclonal antibodies, previously selected to bind either 2-amino-3,8
      dimethylimidazo[4,5-f]quinoxaline (MeIQx) or 2-amino-1-methyl-6-phenylimidazo[4,5
      b]pyridine (PhIP) were evaluated to determine their binding properties with
      several known metabolites of these compounds purified from rat hepatocyte
      cultures. Both 2-N- and 5-substituted MeIQx metabolites were recognized by
      antibodies AIA-2 and AIA-11, while antibodies AIA-1 and AIA-12 bound N
      substituted metabolites only. Anti-PhIP antibodies bound N-hydroxy-PhIP, N
      sulfinamide-glutathione-PhIP and N-hydroxy-glucuronide-PhIP. Immunoaffinity
      columns incorporating these antibodies were used to concentrate and purify both
      the unmetabolized parent compounds and several relatively non-polar metabolites
      from the urine of rats exposed either to MeIQx or PhIP. Several of these
      metabolites corresponded with available standards of previously identified polar
      conjugate metabolites, e.g. N-sulfamate-MeIQx and N(OH)-gluc-PhIP, while others
      are as yet unidentified. Immunoaffinity chromatography is demonstrated as a
      promising means of selectively concentrating metabolites of PhIP and MeIQx from
      urine.

PMID- 1995198
TI  - Clinical management issues in males with sex chromosomal mosaicism and discordant
      phenotype/sex chromosomal patterns.
AB  - The recent availability of Y DNA probes has made it possible to identify two
      forms of 46,XX male syndrome: Y DNA positive and Y DNA negative. The Y DNA
      positive male results from a X;Y translocation with a low recurrence risk; the Y
      DNA negative males are due to a mutation with a high recurrence risk. 46,XX males
      and mosaic forms are phenotypically indistinguishable. A review of the case
      histories for 11 individuals indicates that affected males have highly variable
      genital and nongenital phenotypes. Physical findings may be clearly apparent or
      nonexistent. With the exception of external genitalia, the basis for this
      variability is unknown. It may be related to differences in Y chromatin
      expression as the result of variable inactivation of the X chromosomes, or to the
      existence of minor deletions or point mutations secondary to an exchange of
      genetic material. Common and uncommon clinical problems in these individuals
      require evaluation and follow-up care that is provided through a cooperative,
      interdisciplinary approach.

PMID- 1995197
TI  - Effect of rat liver cytosolic enzymes and cofactors on mutagenicity of 1-amino-8
      nitropyrene.
AB  - 1-Amino-8-nitropyrene (1,8-ANP), a product of 1,8-dinitropyrene metabolism by
      either bacterial or mammalian enzymes, is weakly mutagenic to the 'classical
      nitroreductase'-deficient Salmonella tester strain TA98NR. The addition to the
      test system of rat liver cytosol without cofactors did not produce any effect on
      the 1,8-ANP mutagenic response toward TA98NR strain. Conversely, when both rat
      hepatic cytosol and NADPH (1 mM) were added to the mutagenicity assay, a 10-fold
      increase in 1,8-ANP mutagenic activity was observed. This suggests the
      involvement of rat hepatic cytosolic NADPH-dependent nitroreductase(s) in 1,8-ANP
      mutagenic activation. The addition to the mutagenesis assay of pentachlorophenol,
      an inhibitor of O-acetyltransferase and sulfotransferase, produced a dose
      dependent decrease of 1,8-ANP mutagenic activation, whereas 2,6-dichloro-4
      nitrophenol, a more specific inhibitor of sulfotransferase than O
      acetyltransferase, did not affect the activation of 1,8-ANP to a mutagen at
      concentrations that selectively inhibit only bacterial sulfotransferase. This
      indicates that bacterial O-acetyltransferase but not sulfotransferase plays a
      role in the mutagenic activation of 1,8-ANP. Addition of acetyl co-enzyme A
      (AcCoA) and adenosine 3'-phosphate 5'-phosphosulfate (PAPS), cofactors for O
      acetyl-transferase and sulfotransferase respectively, to the test system caused a
      dose-dependent inhibition of 1,8-ANP mutagenic activation by rat liver cytosol
      and NADPH, probably due to the formation of highly reactive O-acetoxy and N
      sulfate ester derivatives of 1,8-ANP, which react with nucleophilic sites before
      reaching bacterial DNA. This hypothesis was confirmed by DNA covalent binding in
      in vitro experiments showing that both the cofactors AcCoA and PAPS enhanced the
      NADPH/rat liver cytosol-mediated covalent binding of 1,8-ANP to DNA from calf
      thymus 10- and 3-fold respectively. It seems likely that rat hepatic cytosolic
      nitroreductases activate 1,8-ANP to an N-hydroxyarylamine derivative which can be
      further metabolized to mutagenic species by either bacterial or mammalian O
      acetyltransferase.

PMID- 1995199
TI  - Immune functions during treatment of growth hormone-deficient children with
      biosynthetic human growth hormone.
AB  - Immune functions, including cell surface markers, interleukin-2 receptor levels
      and responses of lymphocytes to mitogenic stimulation were evaluated in seven
      growth hormone deficient children ages 4-15 years, during treatment with
      biosynthetically derived human growth hormone. Treatment resulted in a decrease
      in % B cells and in % T total cells and also decreases in most individual
      patients' mitogen responses and interleukin-2 receptor levels. Most of the
      changes noted were transient and similar to those previously demonstrated during
      pituitary-derived human growth hormone treatment. Although not resulting in overt
      clinical manifestations in our patients, we think that potential interactions
      between growth hormone and immune functions need to be considered by physicians
      treating children with growth hormone.

PMID- 1995200
TI  - Reinforcement of incontinent stools in the treatment of encopresis.
AB  - In this paper, fecal incontinence and constipation were treated in two mentally
      retarded individuals using a novel intervention wherein incontinent stools were
      first rewarded in order to increase the frequency of bowel movements. This
      intervention was implemented only after more traditional pediatric and behavioral
      treatments were unsuccessful. The reinforcement of incontinent stools procedure
      resulted in an increase in both the frequency and the number of continent stools
      for both individuals. Hypotheses regarding the failure of previous treatments and
      the success of the current treatment are discussed as well as directions for
      future research.

PMID- 1995201
TI  - "Clear for surgery": current attitudes and practices of pediatricians.
AB  - Two thousand five hundred pediatricians, constituting 10% of active, US-based
      members of the American Academy of Pediatrics, were randomly selected to receive
      a survey of attitudes and practices in the preoperative evaluation of children,
      and communication with anesthesiologists. Of the 790 respondents, 30% routinely
      examine children prior to elective surgery at present, although 60% felt they
      should ideally do so. Only 7.6% had training contacts with anesthesia during
      residency, and only 17% felt their expertise was appreciated by the operating
      team in preparing children for surgery. In clinical management situations, most
      agreed on the anesthetic risks of a recent-onset upper respiratory infection, but
      varied in assessing the risks to a growing premature infant, of a patient with
      Trisomy 21, or of an asthmatic on chronic theophylline. The results suggest that
      pediatricians see their role as important in preoperative preparation of
      children, but lack appropriate training and experience. If "clear for surgery" is
      to be a meaningful activity, greater communication between anesthesiologists and
      pediatricians must be developed.

PMID- 1995202
TI  - Hypocalcaemic stridor in children. How often is it missed?

PMID- 1995203
TI  - Severe hypoproteinemia and edema in association with varicella infection.

PMID- 1995204
TI  - Infantile myelofibrosis with nephromegaly secondary to myeloid metaplasia.

PMID- 1995205
TI  - Congenital rib anomalies in a fetus exposed to carbamazepine.

PMID- 1995206
TI  - The importance of parents' concerns about their child's behavior.
AB  - Parents often complain about children's behavior. Pediatricians may be unsure
      whether to ignore these complaints, counsel parents in-office or refer them to
      mental health services. This study shows a close relationship between parents'
      concerns and measurably significant behavior problems. Methods are provided for
      responding to parents' concerns. These should be useful to pediatricians who are
      often criticized for failing to detect and refer children with mental health
      problems including behavior disturbances.

PMID- 1995207
TI  - Some methodologic and practical issues of reported snoring validity.

PMID- 1995208
TI  - Radiation-associated valvular disease.
AB  - The prevalence of radiation-associated cardiac disease is increasing due to
      prolonged survival following mediastinal irradiation. Side effects of radiation
      include pericarditis, accelerated coronary artery disease, myocardial fibrosis
      and valvular injury. We evaluated the cases of three young patients with evidence
      of significant valvular disease following mediastinal irradiation. One patient
      underwent the first reported successful aortic and mitral valve replacement for
      radiation-associated valvular disease (RAVD) as well as concurrent coronary
      artery revascularization. A review of the literature revealed 35 reported cases
      of RAVD, with only one successful case of valve replacement that was limited to
      the aortic valve. Asymptomatic RAVD is diagnosed 11.5 years after mediastinal
      irradiation compared with 16.5 years for symptomatic patients, emphasizing that
      long-term follow-up is important for patients receiving mediastinal irradiation.
      This study defines a continuum of valvular disease following radiation that
      begins with mild asymptomatic valvular thickening and progresses to severe
      valvular fibrosis with hemodynamic compromise requiring surgical intervention.

PMID- 1995209
TI  - Safety of the transbronchial biopsy in outpatients.
AB  - The objective of our study was to determine the safety of transbronchial biopsy
      (TBB) in nonhospitalized patients. The design was a prospective study of the
      consecutive cases from July 1987 until September 1988 in the setting of a
      university hospital of the third level with 1,800 beds. The patients were a
      consecutive sample of 169 patients who had 184 procedures of fiberoptic
      bronchoscopy (FOB) with TBB performed. They suffered from different diseases:
      lung nodules or masses, diffuse interstitial disease, alveolar condensation, etc.
      An FOB with TBB was performed in immunocompetent outpatients, who were kept under
      observation for four hours and then had a chest roentgenogram taken afterwards.
      We contacted them again after 72 hours to rule out delayed complications. In
      three cases, more than 100 ml of blood were obtained during the FOB, without
      significant hemoptysis being recorded in those patients during the observation
      period; chest pain occurred in 15 patients during the TBB; pneumothorax occurred
      in two patients (1 percent), one of whom required admission to the hospital,
      without requiring chest tube drainage. Other complications are reported
      (bronchospasm, parenchymal hemorrhage, and pneumonia). In conclusion, we consider
      the TBB to be a technique with a low incidence of complications for outpatients,
      so therefore we do not believe that admission to the hospital is mandatory for
      this type of patient, although we do recommend a longer observation period.

PMID- 1995210
TI  - Lung mechanics and gas exchange during exercise in pulmonary sarcoidosis.
AB  - To clarify how lung function at exercise is affected in sarcoidosis, and to
      analyze how exercise studies compare to testing measurements, 63 patients with
      pulmonary sarcoidosis were examined with lung mechanics and arterial blood gases
      during exercise. These findings were compared with simultaneously obtained, but
      previously reported results of the static lung pressure/volume curve and the lung
      resistance/static lung pressure curve. While mechanical variables at maximal
      exercise were as sensitive as those determined by measuring the PstL/V and
      RL/PstL curves, mechanics during spontaneous breathing at rest was less
      sensitive. The derangement of mechanics was more evident than that of arterial
      blood gases. No measurement at rest was a good predictor of working capacity or
      of arterial PaO2. A comprehensive exercise examination may be an alternative to
      resting investigations, which are either more elaborate or less sensitive.

PMID- 1995211
TI  - Individualized aerobic and high intensity training for asthmatic children in an
      exercise readaptation program. Is training always helpful for better adaptation
      to exercise?
AB  - In order to define the role of individualized training intensity in a
      conditioning program for asthmatic children, we have trained seven asthmatics
      (age = 11.4 +/- 1.8 years) at their ventilatory threshold (VTh) intensity level
      for a three-month period (aerobic training) and at maximal intensity also for
      three months (high intensity training). VTh is the point at which a nonlinear
      increase of VE occurs. Another group of seven asthmatics (age = 11.4 +/- 1.5)
      served as control subjects. Cardiopulmonary fitness was determined on a cycle
      ergometer before and after each training session. This study demonstrated that
      aerobic training, correctly adapted to the child's physical ability, induces the
      following: (1) a rapid and marked cardiovascular fitness increase; and (2) a
      decrease in VE over a given work range so that VTh is increased. This is of great
      importance because hyperventilation is a major determinant of exercise-induced
      bronchospasm. In contrast, even if high intensity training is well tolerated in
      an indoor swimming pool, the long-term effects are unsuitable for asthmatic
      children because the decrease of VTh will involve an increase of
      hyperventilation, even when exercise is performed at submaximal intensity.

PMID- 1995212
TI  - Stair climbing as an exercise test to predict the postoperative complications of
      lung resection. Two years' experience.
AB  - The results of a clinically performed preoperative stair climb was compared to
      the presence of postthoracotomy complications in the retrospective hospital
      record review of 54 adult men. The stair climb was a maximum of five flights (125
      steps) performed at the patient's rate and terminated at his request. Pulmonary
      function measurements and facets of the stair climb physiology were also examined
      in reference to the presence, type, and severity of complications experienced.
      Most minor complications such as transient arrhythmias, atelectasis, and
      pneumonia were clearly not predicted by the stair climb performance. The ability
      to climb three flights preoperatively most clearly separated those patients
      having the longer postoperative intubation and hospital stay, greater frequency
      of complications, and cumulative complication score (p less than 0.005). This
      retrospective study did not have sufficient numbers of fatal cardiopulmonary
      complications to exclude the possibility that these may be predicted by the
      results of this simple test.

PMID- 1995213
TI  - Oxygen desaturation during fiberoptic bronchoscopy in pediatric patients.
AB  - STUDY OBJECTIVE: Pulse oximetry was used to measure arterial oxygen saturation
      and the extent of hypoxemia in pediatric patients undergoing FB. DESIGN: Arterial
      oxygen saturation was measured (1) prior to the procedure to provide a baseline
      value, (2) when the bronchoscope was positioned in the nasopharynx, and (3) when
      the bronchoscope was positioned in the mid-trachea. SETTING: Fiberoptic
      bronchoscopy was performed in the Pediatric Special Care Unit or in the Pediatric
      Pulmonary Laboratory using an Olympus BF3C4 fiberoptic bronchoscope with a 3.5-mm
      outer diameter. PATIENTS OR PARTICIPANTS: Thirty-six children who underwent
      diagnostic or therapeutic bronchoscopy for a variety of reasons were evaluated.
      They ranged in age from 6 to 142 months; 20 were male and 16 were female.
      INTERVENTIONS: There were no interventions. MEASUREMENTS AND RESULTS: Of the 36
      patients, 29 experienced a fall in SaO2 levels exceeding 5 percent of baseline
      values. The youngest age group, 6 to 12 months, showed the greatest drop in
      saturation as compared with the other groups. Desaturation was significantly
      increased by midtracheal FB. CONCLUSIONS: A decline in arterial oxygen saturation
      that may be substantial in infants and children undergoing FB examination was
      frequently noted, especially in smaller infants and when the bronchoscope was
      positioned in the mid-trachea. Supplemental oxygen and a brisk procedure time
      will minimize the risk of dangerous hypoxia.

PMID- 1995214
TI  - Spirometric criteria for hospital admission of patients with acute exacerbation
      of COPD.
AB  - Recent studies have demonstrated that there is a high relapse rate for patients
      discharged from the Emergency Department (ED) following treatment of acute
      exacerbation of chronic obstructive pulmonary disease (COPD). Objective criteria
      have not been established to determine when to hospitalize these patients. This
      study evaluated spirometric criteria for that use. Eighty-three patients with an
      acute exacerbation of COPD were studied; 45 percent were admitted to the hospital
      while 17 percent of the patients who were discharged suffered a relapse. An FEV1
      of less than 40 percent of predicted normal identified patients who required
      hospital admission or suffered a relapse with a sensitivity of 0.96, specificity
      of 0.58, and overall accuracy of 0.78. Combining clinical assessment with
      spirometry led to an improvement in specificity to 0.73 with a minimal decrease
      in sensitivity. Patients with an FEV1 of 40 percent or greater of predicted
      normal or no clinical evidence of respiratory distress after treatment may be
      safely discharged from the hospital. Patients not meeting these criteria are at
      high risk for relapse and should either be admitted or have further aggressive ED
      therapy.

PMID- 1995215
TI  - Relative validity of self-reported snoring as a symptom of sleep apnea in a sleep
      clinic population.
AB  - The purpose of this study was to evaluate the relative validity of responses to
      three different questions about snoring as indicators for sleep apnea in a
      population referred to a sleep clinic. Secondary goals were to evaluate the
      meaning of a "don't know" response to these questions and to examine how the
      associations between snoring and sleep apnea are influenced by demographics.
      Results from 1,409 patients in a sleep clinic indicated that nearly all levels of
      estimated snoring frequency were associated with a greater likelihood of sleep
      apnea. In addition, a "don't know" response indicated a likelihood of sleep
      apnea. In the sample from this clinic, sensitivities approximating 90 percent
      were obtained in men, and specificities approximating 90 percent were obtained in
      women, but high diagnostic accuracy (high specificity in men; high sensitivity in
      women) could not be achieved with the three snoring questions used here.
      Generally, associations between snoring and sleep apnea were independent of age
      and sex. Single persons, persons living alone, and persons customarily sleeping
      alone of both sexes all showed associations between self-reported snoring and the
      presence of sleep apnea.

PMID- 1995216
TI  - Pulmonary tolerance of prophylactic aerosolized pentamidine in human
      immunodeficiency virus-infected patients.
AB  - The effects of primary and secondary long-term prophylaxis of Pneumocystis
      carinii pneumonia with aerosolized pentamidine on pulmonary function in HIV+
      patients were evaluated. Eighty-one patients, none of whom were drug addicts or
      had pulmonary Kaposi's sarcoma, were studied. Fifty patients were receiving AP as
      secondary prophylaxis, 36 monthly and 14 twice-monthly; eight patients with a
      history of PCP served as control subjects. Twenty-three patients were receiving
      AP as primary prophylaxis, 12 monthly and 11 twice-monthly. Pulmonary function
      tests, including spirometry, lung transfer capacity for carbon monoxide (Tlco)
      and alveolar-arterial oxygen gradient (P[A-a]O2) were evaluated at M1, ie, one
      month after the diagnosis of PCP, or at the beginning of the AP prophylaxis, and
      then at three-month intervals (M4 to M13). No differences were observed in the
      results of spirometry or P(A-a)O2. Among the patients receiving secondary
      prophylaxis, a significant increase (paired Student's t-test) in Tlco occurred at
      M7 compared to M1 in the group receiving monthly administrations (p less than
      0.01) and in the untreated control group (p less than 0.05); there was no
      significant difference in Tlco at M13 compared to M1 in the 12 patients who
      received monthly administrations for this period or at M7 in the 14 patients
      receiving AP twice-monthly. No significant difference in Tlco was observed at M7
      in the primary prophylaxis groups. These results indicate that pulmonary
      tolerance of AP, as reflected by pulmonary function tests, is good.

PMID- 1995217
TI  - Thoracocardiography. Part 1: Noninvasive measurement of changes in stroke volume
      comparisons to thermodilution.
AB  - The thoracocardiograph (TCG) is a new noninvasive monitoring device that measures
      cardiac oscillations transmitted to the external surface of the thorax. It
      consists of 2.5 cm in height, elastic inductive plethysmographic transducers
      placed transversely in the proximity of the xiphoid process to provide changes in
      cross-sectional area on a transverse plane across the minor ventricular axis.
      Cardiac oscillations synchronous with each heart beat are extracted from the
      respiratory signal during breathing with an ensemble-averaging technique using
      the electrocardiograph as a trigger pulse. The average cardiac waveform at
      locations near the xiphoid process in normal humans has the appearance of a
      ventricular volume curve. The latter is also found in the majority of patients
      with heart disease although in some, outward (dyskinetic) rather than inward
      motion during systole occurs at one or more locations of the TCG transducers. As
      in echocardiography, such findings are consistent with ischemic or scarred
      myocardium invalidating computation of changes in stroke volume from such sites.
      In anesthetized dogs and critically ill patients with normal ventricular wall
      motion, changes in TCG derived ventricular volume waveform amplitudes agreed well
      with changes of thermodilution estimates of stroke volume during atrial pacing
      and fluid loading in the dogs on the one hand and with application of extrinsic
      positive end-expiratory pressure (PEEP) in patients on the other hand.
      Thoracocardiography has the potential for noninvasive, continuous monitoring of
      stroke volume and cardiac output as well as for detection of ischemic or scarred
      myocardium.

PMID- 1995218
TI  - Systemic to pulmonary bronchial blood flow in mitral stenosis.
AB  - We measured systemic to pulmonary bronchial blood flow [Qbr(s-p)] during total
      cardiopulmonary bypass in 15 patients with mitral stenosis and elevated pulmonary
      venous pressure (group A, mean pulmonary wedge pressure = 22.2 +/- 5.4 mm Hg,
      mean +/- SD) and in 15 patients with coronary artery diseases and normal
      pulmonary venous pressure (group B). Qbr(s-p) is the volume of blood accumulating
      in the left side of the heart in the absence of pulmonary and coronary flows.
      This blood was vented through a cannula introduced into the left atrium and
      measured. Qbr(s-p) was 76.3 +/- 13.9 ml/min (2.18 +/- 0.37 percent of
      extracorporeal circulation pump flow) and 22.3 +/- 2.1 (0.63 +/- 0.15) in group A
      and B, respectively (p less than 0.01). During total cardiopulmonary bypass,
      pulmonary venous pressure is approximately atmospheric pressure, and no
      differences in systemic blood pressure, extracorporeal circulation pump flow, and
      airways pressure were observed between group A and B. Therefore, vascular
      resistance through the bronchial vessels draining into the pulmonary circulation
      is reduced in patients with mitral stenosis and elevated pulmonary venous
      pressure.

PMID- 1995219
TI  - Changes in left ventricular diastolic filling patterns by Doppler
      echocardiography in cystic fibrosis.
AB  - The onset of cor pulmonale is a common terminal finding in patients with cystic
      fibrosis. Since Doppler echocardiography can detect changes in diastolic filling
      patterns prior to the onset of either systolic dysfunction or clinical symptoms,
      we utilized this technique to determine whether detectable changes in left
      ventricular diastolic filling patterns exist in patients with cystic fibrosis.
      Among 25 patients, the proportion of left ventricular filling attributable to
      atrial contraction was significantly increased when compared with age-matched
      control individuals. When filling patterns were compared with severity of
      pulmonary disease, worsening pulmonary disease was directly correlated to shifts
      in left ventricular filling patterns. We conclude that changes in left
      ventricular patterns of relaxation are detectable early in the course of cystic
      fibrosis and that such changes are probably progressive. Early detection could
      lead to therapeutic trials designed to improve left ventricular filling and delay
      the onset of overt cor pulmonale.

PMID- 1995220
TI  - Catheter-induced tricuspid regurgitation. Incidence and clinical significance.
AB  - The incidence and severity of catheter-induced tricuspid regurgitation has not
      been studied extensively. Given the frequency with which right heart catheters
      are employed to measure cardiac output, it is important to know whether the
      severity of catheter-induced tricuspid regurgitation is sufficient to invalidate
      the measurement of thermodilution cardiac output. Accordingly, the purpose of the
      present prospective study was to determine the incidence and severity of catheter
      induced tricuspid regurgitation in 25 men (mean age, 58.1 +/- 1.4 years) using
      Doppler ultrasound. The tricuspid valve was interrogated from two orthogonal
      views using pulsed-wave and color flow Doppler, either in the presence or absence
      of a 7-French catheter across the tricuspid valve. The severity of catheter
      induced tricuspid regurgitation was graded semiquantitatively using a validated
      scoring system. Pulsed-wave Doppler studies showed that the incidence of catheter
      induced tricuspid regurgitation was 48 percent, and that the average tricuspid
      regurgitation score increased from 0.41 +/- 0.16 to 0.61 +/- 0.17 (p less than
      0.01). Color flow Doppler studies showed similar findings. Further, the incidence
      of catheter-induced tricuspid regurgitation was not related to the patient's
      underlying hemodynamic status or right ventricular geometry. In conclusion, this
      study shows for the first time that the quantitative extent of catheter-induced
      tricuspid regurgitation is small, and is therefore unlikely to be important
      clinically, particularly with regard to the assessment of thermodilution cardiac
      output.

PMID- 1995221
TI  - Pneumocystis carinii pneumonia complicating multiple myeloma.
AB  - Pneumocystis carinii pneumonia complicated the course of two patients with
      multiple myeloma. The diagnosis was established in both cases by bronchoalveolar
      lavage, which demonstrated the typical pneumocysts. Clinical and roentgenographic
      improvement in both patients was observed following a course of trimethoprim
      sulfamethoxazole. One patient had lymphocyte subsets performed with a CD4/CD8
      ratio of 0.8; both patients were HIV antibody-negative by ELISA. Both patients
      tolerated prophylactic TMP-SMX given concurrently with the subsequent
      chemotherapy for myeloma. We suggest that the immune defect seen in multiple
      myeloma may have placed these patients at risk for opportunistic infections such
      as P carinii pneumonia; however, as opposed to patients with AIDS, our patients
      tolerated therapy with TMP-SMZ quite well.

PMID- 1995222
TI  - Impaired exercise capacity in adults with moderate scoliosis.
AB  - We measured lung function and exercise tolerance in 15 adults with moderate
      kyphoscoliosis (thoracic curvatures between 25 degrees and 70 degrees, mean +/-
      SD = 46.93 degrees +/- 14.02 degrees). Forced vital capacity showed a slight
      reduction from values predicted from age and sex matched control subjects (3.39
      +/- 1.06 vs 4.06 +/- 0.82 L, p less than 0.05). However, exercise tolerance was
      significantly lower than previously reported in healthy adults (VO2max = 31.60 +/
      9.12 vs 37.07 +/- 4.91 ml/kg/min, p less than 0.05). Despite the reduced
      exercise tolerance, the ratio of maximum tidal volume to vital capacity
      (VTmax/VC) was similar to that observed in healthy adults. The mean dyspnea index
      (VEmax/MVV) was also normal at 69.4 +/- 19.0. Hypoxic and hypercapnic ventilatory
      responses were within predicted normal limits at 0.67 +/- 0.37 L/min-1 fall in
      SaO2-1 and 1.67 +/- 0.92 L/min-1 mm Hg PCO2(-1). We conclude that the impairment
      of exercise performance found in adults with moderate scoliosis cannot be
      attributed to any important ventilatory limitation, abnormality in lung volume,
      or impaired chemoreceptor sensitivity. We suggest that the reduced VO2max likely
      arises from deconditioning and lack of regular aerobic exercise.

PMID- 1995223
TI  - Diagnosis of disease caused by Mycobacterium avium complex.
AB  - Isolation of Mycobacterium avium complex from sputum specimens in association
      with the appearance of a new cavitary (or infiltrative) lesion was studied in 299
      patients from whom the organism was isolated one or more times. Of the patients
      studied, 114 showed only single isolation. Of these 114, only two patients (2
      percent) had association with appearance of a cavitary lesion. Of 29 patients who
      showed two isolations, 26 (90 percent) had the association. Of 40 patients who
      showed three isolations, 39 (98 percent) had the association. All 116 patients
      who showed four or more isolations had the association with appearance of a
      cavitary lesion. Accordingly, of a total of 185 patients who showed two or more
      isolations, 181 (98 percent) had the association. Of these 181, 176 (97 percent)
      showed two or more isolations in the sputum examinations made in the initial
      three days. Therefore, the sputum examination in the first three days after onset
      of disease is most important for the diagnosis of disease caused by Mycobacterium
      avium complex. Since the probability that casual isolation of the organism occurs
      twice is extremely low, we can make the diagnosis of pulmonary infection caused
      by this organism by evidence of two or more isolations of the organism in the
      first few days after the onset of disease, which is associated with appearance of
      a new cavitary (or infiltrative) lesion. Moreover, theoretical consideration made
      in this study has led us to conclude that patients who have had a single
      isolation of the organism together with a new cavitary lesion should be regarded
      as having an infection.

PMID- 1995224
TI  - Erythromycin reduces the severity of bronchial hyperresponsiveness in asthma.
AB  - It has been demonstrated that bronchial hyperresponsiveness is a characteristic
      feature of bronchial asthma, and airway inflammation plays an important role in
      bronchial hyperresponsiveness. Erythromycin is an antibiotic extensively used
      worldwide which is also reported to have anti-inflammatory action. This study was
      designed to clarify whether erythromycin could favorably alter bronchial
      responsiveness in patients with bronchial asthma. To estimate bronchial
      responsiveness, histamine challenge was performed in 23 patients with bronchial
      asthma (atopic type, 11; nonatopic type, 12). All patients were treated for ten
      weeks with erythromycin, 200 mg three times daily, orally. After ten weeks'
      treatment, PC20, an index of bronchial sensitivity, was increased significantly.
      There was no difference between atopic and nonatopic patients in the improvement
      of PC20. It was concluded that erythromycin reduces the severity of bronchial
      responsiveness in patients with bronchial asthma.

PMID- 1995225
TI  - IL-1 and IL-1 inhibitory activity in the culture supernatants of alveolar
      macrophages from patients with interstitial lung diseases.
AB  - Under normal conditions, the release of interleukin 1 (IL-1) and IL-1 inhibitors
      play a role in tissue homeostasis. We have already reported an increase in IL-1
      activity and a decrease in IL-1 inhibitory activity (IHA) in the supernatants of
      alveolar macrophages from healthy long-term smokers as compared with healthy
      nonsmokers. In this study, we report an alteration in the release of IL-1 and IL
      1 IHA from alveolar macrophages in patients with interstitial lung diseases
      (sarcoidosis and idiopathic pulmonary fibrosis [IPF]). IL-1 activity released
      from alveolar macrophages stimulated by lipopolysaccharide was increased in
      patients with active sarcoidosis (mean +/- SD, 2.52 +/- 1.33 U/ml [n = 6] vs 1.38
      +/- 0.62 U/ml [n = 15] for healthy non-current smokers [HNS]; p less than 0.05).
      IL-1 IHA released from alveolar macrophages was significantly different among the
      groups examined: a decrease of IL-1 IHA occurred in patients with active
      sarcoidosis (61.4 +/- 19.2 [n = 6] vs 85.9 +/- 13.9 percent:HNS; p less than
      0.05) and IPF (64.7 +/- 18.5 [n = 9]; p less than 0.05). Prednisolone in the
      culture medium at physiologic concentrations suppressed the release of IL-1 and
      enhanced the release of IL-1 IHA. IL-1 IHA inhibited not only mouse thymocyte
      proliferation but also human fibroblast proliferation in the presence of IL-1.

PMID- 1995226
TI  - Patterns of resource consumption in medical intensive care.
AB  - Intensive care is being scrutinized as a major factor in increasing health care
      costs. We examined 404 consecutive admissions to the medical ICUs at a university
      medical center to study patterns of consumption of ICU resources and the
      proportion of resources used by patients admitted for monitoring only. We found a
      skewed distribution of ICU resource consumption, with the "high-cost" 8 percent
      using as many ICU resources as the "low-cost" 92 percent. Forty-one percent of
      admissions did not receive acute ICU treatments, but these admissions consumed
      less than 10 percent of ICU resources. Reducing the number of patients admitted
      for monitoring will have a relatively small impact on hospital charges. Since
      over 70 percent of the high-cost patients died, improved understanding of
      prognosis and better physician-patient communication may substantially reduce the
      proportion of critical care resources expended on futile treatment.

PMID- 1995227
TI  - Reversible decrease of oxygen consumption by hyperoxia.
AB  - The hemodynamic and metabolic effects of 90 minutes normobaric hyperoxia were
      studied in 20 critically ill patients (11 septic, 9 nonseptic) requiring
      mechanical ventilation with inspired O2 fraction (FIO2) less than 0.40. Thirty
      minutes after increasing the FIO2 to 1.0, arterial PO2 had increased from about
      100 to about 400 mm Hg, and whole body oxygen uptake (VO2) was decreased 10
      percent (p less than 0.05) due to an 18 percent decrease in O2 extraction ratio.
      During the subsequent 60 minutes of hyperoxia, there was no further significant
      change in VO2. Cardiac index did not change in hyperoxia, but it increased 10
      percent (p less than 0.05) in recovery as systemic vascular resistance decreased.
      VO2 returned to baseline after 30 minutes recovery at original FIO2 due to
      increased O2 extraction as well as the increased cardiac output. The decrease in
      VO2 without a decrease in O2 delivery may reflect maldistribution of blood flow
      and functional O2 shunting to protect tissue from unphysiologically high PO2.
      While brief oxygenation is advisable before periods of hypoventilation, the
      present data suggest that hyperoxic ventilation in these patients with already
      adequate O2 delivery was counterproductive.

PMID- 1995228
TI  - Right ventricular dysfunction in chronic obstructive pulmonary disease.
      Evaluation and management.
AB  - Cor pulmonale is an important consequence of COPD. Although the incidence is not
      precisely known, it is seen more frequently in patients with hypoxemia, CO2
      retention and severely reduced FEV1. When present, it limits peripheral oxygen
      delivery, increases shortness of breath, and reduces exercise endurance. It is
      also associated with higher mortality rates independent of other prognostic
      variables. Numerous factors may contribute to the development of cor pulmonale in
      patients with COPD, but its primary cause is chronic alveolar hypoxia resulting
      in pulmonary vasoconstriction, vascular remodeling and pulmonary hypertension.
      The physical exam, chest radiograph and ECG may be helpful in detecting the
      presence of cor pulmonale, but because of anatomic changes that occur in the
      chest, these tests are often insensitive in patients with COPD. Noninvasive
      diagnostic techniques utilizing Doppler echocardiography and radionuclide
      angiography allow for detection of RV dysfunction at an earlier stage and in most
      cases, preclude the need for right heart catheterization. LTO2 is the only
      therapy shown to improve survival in patients with COPD. However, statistical
      proof correlating improvements in pulmonary hemodynamics with increased survival
      is lacking. Bronchodilators, such as the beta 2 agonists and especially
      theophylline, may have beneficial effects on pulmonary hemodynamics in addition
      to their effect on respiratory function and are useful in COPD when RV
      dysfunction is present. Diuretics and phlebotomy are also useful in improving
      symptoms in appropriate patients. Vasodilators such as calcium channel blockers
      and ACE-inhibitors may improve pulmonary hemodynamics acutely, but may lower
      arterial PO2 by worsening ventilation-perfusion matching or blunt the improvement
      in pulmonary hemodynamics seen with supplemental oxygen. The long-term benefits
      of these agents have not been proven and their routine use in patients with cor
      pulmonale due to COPD cannot be recommended.

PMID- 1995229
TI  - Acute aortic dissection.

PMID- 1995231
TI  - Chest pain and thoraco-abdominal mass.

PMID- 1995230
TI  - Indications for spirometry in outpatients with respiratory disease.
AB  - It has been suggested that spirometry should be incorporated into the routine
      examination of every patient, analogous to obtaining vital signs. To determine
      the impact of spirometry on the management of outpatients with respiratory
      disease, spirometry was performed on 150 consecutive patients (123 men and 27
      women, mean age 57 +/- 12 years) seen in our pulmonary disease outpatient
      clinics. Patients with obstructive (n = 75), restrictive (n = 31), mixed (n = 26)
      or other respiratory diseases (n = 18) were initially assessed by history and
      physical examination and classified as improved, stable, or worse compared to
      previous visits. A clinical management plan (CMP) was formulated based on this
      initial evaluation. Spirometric results were then made available to the examiner
      who could then make changes in the proposed CMP. The addition of spirometric
      results caused alteration of the CMP in only eight (5 percent) patients; in the
      remaining 142 patients, results did not affect the CMP. Two clinical findings
      identified those patients whose CMP was most likely to be altered by spirometry:
      severity of lung dysfunction (determined from previous spirometry) and
      deterioration of clinical status (judged by history and physical examination). Of
      the eight patients whose CMP was changed after review of spirometry, six (75
      percent) had previous severe ventilatory dysfunction (FEV1 or FVC less than or
      equal to 40 percent of predicted or FEV1/FVC ratio less than or equal to 0.40).
      In 6 of 38 patients (16 percent) with severe ventilatory dysfunction, CMP was
      altered after spirometry while only 2 of 112 patients (1.8 percent) with mild or
      moderate dysfunction had changes in their CMP. Patients who were clinically
      assessed as worse compared to their previous visit were more likely to have their
      CMP altered after review of spirometry when compared to those considered improved
      or stable by a ratio of 6:1. These results suggest that spirometry is most likely
      to supplement the physician's history and physical examination in the management
      of outpatients with pulmonary disease when the initial evaluation suggests that
      the patient has clinically deteriorated since the previous clinic visit, or when
      he or she has previous severe ventilatory dysfunction.

PMID- 1995232
TI  - Myocardial infarction with multiple complications. Problems in management.

PMID- 1995233
TI  - Detection and localization of early lung cancer by imaging techniques.

PMID- 1995234
TI  - Erythema and edema of the breast with respiratory failure.

PMID- 1995235
TI  - Barium sulfate bronchography. Report of a complication.
AB  - Alveolarization of the barium sulfate and subsequent retention of barium sulfate
      for years was demonstrated in three patients in whom dilute suspension of barium
      sulfate in water was used for bronchography. Pathologic examination in one
      patient showed barium sulfate within macrophages in the alveolar spaces and walls
      and in the perivascular and peribronchial interstitium. Since the residual barium
      sulfate interferes with imaging procedures of the lungs, it represents an
      unwanted event in patients with pulmonary disease. High-resolution computed
      tomography is the preferred method of evaluating for bronchiectasis. If
      bronchogram is performed, it should be performed after bronchoscopy using oily
      propyliodone (Dionosil).

PMID- 1995236
TI  - Sleepwalking precipitated by treatment of sleep apnea with nasal CPAP.
AB  - A 33-year-old man with a long history of snoring, observed apneic episodes, and
      excessive daytime sleepiness, underwent all-night polysomnography, which
      demonstrated severe obstructive sleep apnea. During the nasal CPAP trial, two
      episodes of sleepwalking were observed during a period of delta sleep rebound.

PMID- 1995237
TI  - Miliary tuberculosis presenting as hepatic and renal failure.
AB  - A 67-year-old man developed hepatic and renal failure over a six-day period.
      Despite full supportive measures, he died on his 11th day of hospitalization with
      fulminant DIC and hepatic, renal, and respiratory failure. Postmortem examination
      revealed acid-fast bacilli in virtually all organ systems. Miliary tuberculosis
      should be considered as a potentially treatable cause of hepatic failure.

PMID- 1995238
TI  - Paradoxic air embolism in the absence of an intracardiac defect.
AB  - A 58-year-old man experienced paradoxic air embolism with passage of air from the
      systemic venous to the systemic arterial circulation with subsequent stroke and
      death. No intracardiac shunt was present. Pulmonary fibrosis concomitant with
      severe pulmonary arterial hypertension appears to have been responsible for the
      air traversing the pulmonary capillary bed. This unusual outcome of a complicated
      central venous catheterization must be borne in mind and guarded against in
      similar patients.

PMID- 1995239
TI  - Hypercapnic respiratory failure due to L-tryptophan-induced eosinophilic
      polymyositis.
AB  - A 24-year-old man presenting with fever, rash, and myalgias subsequently
      developed hypercapnic respiratory failure and severe limb muscle weakness. Muscle
      biopsy revealed eosinophilic myositis, due to the ingestion of large quantities
      of L-tryptophan as a dietary supplement. Complete recovery occurred with
      corticosteroid administration. Significant involvement of the respiratory muscles
      can be a predominant feature of this newly described disease entity.

PMID- 1995240
TI  - Left atrial bacterial mural endocarditis.
AB  - An unusual case of Staphylococcus aureus endocarditis confined to the mural left
      atrium is presented. Echocardiographic studies revealed a 1.5 x 2.0-cm vegetation
      mimicking a myxoma situated in the path of a mitral regurgitant jet on a color
      Doppler test. Emboli to upper and lower extremities and brain complicated the
      patient's preoperative course. Surgical excision and pathologic examination
      confirmed this rare occurrence.

PMID- 1995241
TI  - Subcutaneous and mediastinal emphysema associated with hypersensitivity
      pneumonitis.
AB  - We report a rare case of a patient in whom severe subcutaneous and mediastinal
      emphysema occurred in association with summer-type hypersensitivity pneumonitis
      and in whom overdistention or disruption of alveoli with obliteration of the
      respiratory bronchioles was revealed on open lung biopsy. This case suggests that
      obstructive bronchiolitis with hypersensitivity pneumonitis is an etiologic
      factor of mediastinal emphysema.

PMID- 1995242
TI  - Potentially fatal asthma and syncope. A new variant of Munchausen's syndrome in
      sports medicine.
AB  - We report a case of Munchausen's syndrome in a 19-year-old female college athlete
      who presented with potentially fatal asthma and recurrent syncopal episodes.
      Failure to control her asthma with the appropriate medications and the lack of
      objective findings on both physical examination and diagnostic testing raised the
      possibility of factitious disease. Munchausen's syndrome, although not described
      with any frequency in asthmatic patients, should be considered in the
      differential diagnosis of those patients refractory to aggressive medical
      management.

PMID- 1995243
TI  - Central neurogenic hyperventilation in invasive laryngeal carcinoma.
AB  - We describe a patient with central neurogenic hyperventilation secondary to
      extension of a laryngeal tumor into the base of the brain, resulting in extrinsic
      compression of the medulla. Such an association has not been previously
      described. Unique features which distinguish this patient from previously
      reported cases are emphasized. Possible mechanisms involved in pathogenesis, as
      well as types of therapy, are outlined.

PMID- 1995244
TI  - Hypertrophic osteoarthropathy in association with pulmonary tuberculosis.
AB  - Three white male patients with advanced cavitary pulmonary tuberculosis presented
      with HOA. No other pathology to explain the osteoarthropathy was detected. The
      osteoarthropathy responded symptomatically to NSAI drugs and treatment of
      tuberculosis but resolved radiologically in only one patient.

PMID- 1995245
TI  - Fatal adult respiratory distress syndrome following successful treatment of
      pulmonary strongyloidiasis.
AB  - Hyperinfection with Strongyloides stercoralis occurs mostly in immunocompromised
      patients, including those treated with systemic steroids. A case of Strongyloides
      induced adult respiratory distress syndrome was recently reported, and we now
      report a case in which fatal ARDS appeared to result from the successful therapy
      of massive parasitic infection.

PMID- 1995246
TI  - Pleural Pneumocystis carinii infection.
AB  - Extrapulmonary Pneumocystis carinii infection is a rare occurrence in patients
      with AIDS. Pleural involvement has been demonstrated in only one case, and this
      occurred after pneumothorax. This is a case report of pleural pneumocystosis in a
      patient with AIDS who did not have a pneumothorax.

PMID- 1995247
TI  - Management of an extensive tracheoesophageal fistula by cervical esophageal
      exclusion.
AB  - Giant tracheoesophageal fistulae occurring in ventilator-dependent patients
      usually result in significant ventilatory embarrassment. Cervical exclusion of
      the fistula can safely control the fistula and quickly restore adequate
      ventilation to these critically ill patients.

PMID- 1995248
TI  - Coronary artery fistula formation secondary to permanent pacemaker placement.
AB  - We present the findings in two patients who apparently developed a coronary
      artery fistula as a complication of an endocardial pacing electrode. This
      complication may actually be occurring more frequently than recognized because
      the patient may be asymptomatic or minimally symptomatic and therefore not
      undergo a coronary angiogram. Awareness of this potentially serious complication
      is important and stresses the need for proper electrode placement without excess
      pressure on the tip.

PMID- 1995249
TI  - Unusual presentation of recurrent Wegener's granulomatosis.
AB  - A 65-year-old woman presented with recurrent Wegener's granulomatosis following
      two years of immunosuppressive therapy and three years of complete remission. At
      her initial presentation, she had a characteristic x-ray picture showing multiple
      nodules with total resolution of these findings at three months. Five years
      later, at the time of clinical relapse, her chest x-ray film showed bilateral
      diffuse infiltrative disease. This change in radiologic presentation upon relapse
      of Wegener's has not previously been reported. Other unusual features include
      diffuse infiltrates as the pulmonary presentation and the long interval between
      cessation of therapy and relapse. We review the radiologic manifestations of
      Wegener's granulomatosis.

PMID- 1995250
TI  - Venous air embolism. Diagnosis by spontaneous right-sided contrast
      echocardiography.
AB  - This report describes the definitive diagnosis of venous air-embolism by
      documentation of spontaneous echo contrast in the right cardiac chambers
      following removal of a jugular venous catheter in a patient with hepatic failure.
      This complication was potentiated by the presence of concurrent hepatic
      coagulopathy which prejudiced effective hemostasis at the central venous puncture
      site.

PMID- 1995251
TI  - A standardized method for determination of who should be listed as authors on
      scholarly papers.
AB  - A handy method is described of selecting among the inevitable onslaught of 100 to
      200 potential coauthors that mysteriously appear whenever a journal article is
      submitted for publication. The "relative authorship weighting scale" helps to
      decide who actually qualifies as an author and serves as an objective means of
      determining the appropriate order in which these various goldbrickers should be
      listed on the manuscript.

PMID- 1995252
TI  - Severe pulmonary hypertension with diffuse smooth muscle proliferation of the
      lungs.

PMID- 1995253
TI  - Pulmonary hamartoma syndrome.

PMID- 1995254
TI  - Adenosine deaminase and lymphocytic populations.

PMID- 1995255
TI  - Pleuroscopy--an underestimated diagnostic procedure in pleural effusion.

PMID- 1995256
TI  - Occurrence of mitral valve prolapse in nonsmoker spontaneous pneumothorax
      patients.

PMID- 1995257
TI  - On drugs and dilators for achalasia.

PMID- 1995258
TI  - Medical treatment of esophageal achalasia. Double-blind crossover study with oral
      nifedipine, verapamil, and placebo.
AB  - Calcium channel blockers have been previously shown to decrease lower esophageal
      sphincter (LES) pressure and improve symptoms in achalasia. We performed a
      placebo-controlled, double-blind, crossover study to assess the effects of oral
      nifedipine and verapamil on LES pressure, amplitude of esophageal body
      contraction, and clinical symptomatology in eight patients with symptomatic
      achalasia diagnosed by endoscopy, barium swallow, and manometry. Patients were
      randomized to receive up to 20 mg nifedipine, 160 mg verapamil, or placebo and
      underwent esophageal manometry before (baseline) and after four weeks on each
      drug. Diary cards were kept to record and grade symptoms and drug plasma level
      determinations were correlated with manometric and clinical findings. Both
      nifedipine and verapamil caused a statistically significant decrease in mean LES
      pressure, but only nifedipine caused a significant decrease in the amplitude of
      contractions of the smooth muscle portion of the esophagus. No statistically
      significant differences in the overall clinical symptomatology were noted with
      any of the drugs, although some individual improvements in dysphagia and chest
      pain were noted. We conclude that, despite the reduction in LES pressure and
      contraction amplitude of the distal esophageal body, oral nifedipine and
      verapamil do not significantly alter the clinical symptomatology of patients with
      achalasia.

PMID- 1995259
TI  - Management of dysphagia in suspected esophageal motor disorders.
AB  - Fifty-three patients suffering from dysphagia because of suspected esophageal
      motor disorders were treated by pneumatic dilatation using the Rider-Moeller
      technique. Fifteen had achalasia demonstrated by manometric studies. Forty-nine
      of them had remarkable clinical improvement after the procedure. During the mean
      period of follow-up (average 5 years, range 1-11), 75% of the patients needed a
      new dilatation, with a delay of two years. The results of the dilatation were
      excellent or good in 80% of the cases. Early complications consisted in two
      esophageal perforations surgically treated. There was no mortality. We did not
      observe late complications of the procedure. We conclude that pneumatic
      dilatation should be the initial procedure in the treatment of dysphagia in
      suspected esophageal motor disorders.

PMID- 1995260
TI  - Reevaluation of manometric criteria for vigorous achalasia. Is this a distinct
      clinical disorder?
AB  - Clinical and manometric data from 97 consecutive patients with idiopathic
      achalasia were analyzed to see if a distinct subset with vigorous achalasia could
      be identified. Statistical analyses failed to detect a unique group of subjects
      based on the distribution of contraction wave amplitudes alone. Because of this,
      patients falling above the 95th percentile (N = 4, mean wave amplitude greater
      than 100 mm Hg for each) were compared with those having mean amplitudes above
      the conventional threshold for the diagnosis of vigorous achalasia (mean
      amplitude 60-100 mm Hg, N = 4), and with the remainder (N = 89, mean amplitude
      less than 60 mm Hg). Subjects with mean amplitudes less than 60 mm Hg and with
      mean amplitudes 60-100 mm Hg closely resembled each other in all measured
      clinical features, whereas subjects with mean amplitudes greater than 100 mm Hg
      were all male, were older (67 +/- 4 years vs 47 +/- 2 years; P less than 0.01),
      and appeared to have somewhat longer duration of symptoms when compared with the
      remainder (82 +/- 41 vs 44 +/- 10 months; P = 0.4). Chest pain and other
      esophageal symptoms, basal and residual lower sphincter pressures, and response
      to first treatment did not differ among the three groups. These data indicate
      that high-fidelity manometry techniques identify a rare subset of achalasia
      patients with mean contraction amplitudes exceeding 100 mm Hg that, although
      older and possibly with greater duration of symptoms, presents similarly to
      others with idiopathic achalasia. Outcome from conventional treatment is also
      similar for the "vigorous" and "nonvigorous" patients, making the distinction of
      questionable value.

PMID- 1995261
TI  - Esophageal candidiasis in AIDS. Successful therapy with clotrimazole vaginal
      tablets taken by mouth.
AB  - In this paper we describe the results of oral therapy of esophageal candidiasis
      with clotrimazole vaginal tablets in 25 homosexual men with AIDS, of whom 19 had
      oral candidiasis and 16 had esophageal symptoms. Therapy with clotrimazole
      vaginal tablets, 100 mg, taken by mouth cleared the esophageal symptoms, oral
      candidiasis, and esophageal lesions completely in all 25 men. Clotrimazole
      vaginal tablets are a useful alternative to other antifungal agents for the
      treatment of esophageal candidiasis in AIDS patients.

PMID- 1995262
TI  - Effect of intraesophageal location and muscarinic blockade on balloon distension
      induced chest pain.
AB  - Intraesophageal balloon distension has been introduced recently as a provocative
      test in the assessment of patients with noncardiac chest pain. In order to
      examine the effect of balloon location and muscarinic blockade on distension
      induced pain, 10 asymptomatic male volunteers were studied on two separate days
      using a low-compliance perfused manometry system that incorporated a silicone
      rubber balloon. Five-second-duration balloon distensions using balloon volumes of
      2.5, 5, 7.5, and 10 ml of air were performed with the balloon located both 16 cm
      (proximal site) and 6 cm (distal site) above the lower esophageal sphincter (LES)
      before and after administration of atropine (10 micrograms/kg intravenously) or
      placebo in a randomized double-blind fashion. A standardized scoring system was
      used to assess the balloon distension-induced pain. Pain scores varied directly
      with balloon volume but were consistently higher with the balloon located at the
      proximal site versus the distal site. This was not associated with any
      differences in intraballoon pressures between the two sites; however, contraction
      amplitude orad to the balloon was greater with balloon distension at the proximal
      site. Atropine significantly decreased pain sensation scores with the balloon
      located distally but not proximally. This attenuation was not associated with
      significant changes in intraballoon pressures; however, contractions orad to the
      balloon were markedly inhibited by atropine with distal but not with proximal
      distension. These studies indicate that balloon distension-induced pain varies
      depending on the location of distension. This difference is not explained by
      differences in esophageal wall tension at the site of distension.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1995263
TI  - Relationship between plasma and hepatic cytosolic levels of ornithine
      decarboxylase (ODC) and thymidine kinase (TK) in 70% hepatectomized rats.
AB  - Ornithine decarboxylase (ODC) and thymidine kinase (TK) are enzymes important for
      DNA synthesis, a process that is critical for cell renewal and regeneration. As
      such, they already have been used as surrogate markers of regeneration in tissue.
      In the present study, the activity of these two enzymes in plasma of rats and
      regenerating hepatic tissue following a 70% hepatectomy were determined. The
      results demonstrate that the changes in these enzyme activities in plasma reflect
      the changes obtained in the liver tissue. Thus, blood levels of ODC and TK can be
      used as a less invasive and nondestructive means of monitoring the regenerative
      response of the liver and possibly other tissues.

PMID- 1995264
TI  - Species differences in hepatic pulmonary and upper gastrointestinal tract
      biotransformation enzymes on long-term feeding of masheri--a pyrolyzed tobacco
      product.
AB  - The activities of several activating enzymes and that of glutathione S
      transferase as well as levels of glutathione were measured in the upper
      alimentary tract, lung, and liver of Swiss mice, Sprague-Dawley rats, and Syrian
      golden hamsters treated with 10% masheri (pyrolyzed tobacco) in diet for 20
      months. Significant increase in activities of phase I activating enzymes and a
      remarkable decrease in the phase II detoxification system in most extrahepatic
      tissues of the treated animals of all three species was observed. These
      observations suggest that the prolonged exposure to environmental
      xenobiotics/carcinogens affects the drug-metabolizing enzymes of the
      gastrointestinal tract, which may be an important factor in determining the
      susceptibility of different organs to carcinogen exposure.

PMID- 1995265
TI  - Natural killer cell activity in patients with liver cirrhosis relative to
      severity of liver damage.
AB  - To evaluate the role of severe liver damage on natural killer cell activity, 29
      patients with liver cirrhosis were examined. The natural killer cell activity was
      measured with a 4-hr chromium release assay, and the K562 cell line was employed
      as target cells. The natural killer cell activity was significantly decreased in
      cirrhotic patients compared with normal controls and patients with chronic active
      hepatitis. Cirrhotic patients with Pugh's C grade of severity of liver disease
      had lower natural killer cell activity. The depression of natural killer cell
      activity in cirrhotic patients was inversely correlated with prothrombin time
      ratios, and the natural killer cell activity in cirrhotic patients with hepatic
      encephalopathy was lower than in patients without hepatic encephalopathy. Thus,
      the diminished natural killer cell activity in cirrhotic patients might be
      related to the severity of liver damage.

PMID- 1995266
TI  - Demonstration of two distinct subsets of gastric varices. Observations during a
      seven-year study of endoscopic sclerotherapy.
AB  - Over a seven-year period, assessment of gastric varices was made on 225 patients
      receiving endoscopic sclerotherapy for variceal hemorrhage. Of 170 patients with
      complete data, gastric varices were observed in 26 (15.3%). Importantly, two
      distinct subsets of gastric varices were identified: varices distal to the
      gastroesophageal junction without extension into the fundus, termed "junctional
      varices," occurred in 11.2%, and varices that were confined only to the fundus,
      termed "fundal varices," occurred less frequently in 4.1%. Although rebleeding
      was increased in both subsets of gastric varices, junctional varices were more
      amenable to sclerotherapy. Patients with fundal varices (N = 7) had a
      significantly higher rebleeding rate, increased complications with sclerotherapy,
      and significantly decreased survival (P less than 0.005) when compared to
      patients with esophageal varices alone (N = 87) who were followed for more than
      three months. Cumulative survival was not significantly different (P less than
      0.08) in patients with junctional varices (N = 19) when compared with patients
      with esophageal varices alone. We conclude that not all patients with gastric
      varices have a poor result with sclerotherapy. Recognition of these subsets may
      improve treatment strategies in patients with gastric varices.

PMID- 1995267
TI  - Bile acids in human plasma interfere with cholecystokinin bioassay using
      dispersed pancreatic acini.
AB  - A bioassay using dispersed pancreatic acini was used to measure fasting plasma
      cholecystokinin (CCK) concentrations in 105 patients with various kinds of
      gastrointestinal diseases, 17 patients with diabetes mellitus, and 6 healthy
      volunteers. High plasma CCK bioactivities were observed in patients with
      obstructive jaundice, choledocolithiasis, and primary biliary cirrhosis. Twenty
      three samples with high CCK bioactivities were assayed by the same bioassay after
      the addition of a specific CCK antagonist and by a CCK radioimmunoassay in order
      to determine whether the high CCK-like bioactivity was due to circulating CCK or
      other factors. High CCK bioactivities were partially inhibited by the specific
      CCK antagonist, CR-1409, but the activities were not totally abolished. The
      residual bioactivities (not inhibited by CR-1409) correlated with plasma bile
      acid concentrations. The inhibitable CCK bioactivities correlated with plasma CCK
      levels obtained by radioimmunoassay. Although the bioassay using dispersed
      pancreatic acini has several advantages for measuring plasma CCK, this method
      overestimates CCK bioactivities in patients with high plasma bile acid
      concentrations.

PMID- 1995268
TI  - Biliary pain in postcholecystectomy patients without biliary obstruction. A
      prospective radionuclide study.
AB  - Biliary pain without obvious biliary obstruction is common in postcholecystectomy
      patients. We studied 20 symptomatic patients with episodes of biliary-type pain
      after cholecystectomy (all having undergone endoscopic retrograde
      cholangiography), and in 18 asymptomatic postcholecystectomy controls. We
      performed quantitative hepatobiliary radionuclide analysis with dimethyl
      imidodiacetic acid. From a series of 90 dynamic images at 1-min intervals using a
      gamma camera coupled to a computer, time-activity curves were produced in regions
      of interest in the liver, intrahepatic biliary tree, common duct, and heart, from
      which quantitative biliary excretion indexes were obtained. The results
      demonstrate a biliary kinetic dysfunction in patients with postcholecystectomy
      pain without morphological abnormalities.

PMID- 1995269
TI  - Ulcerative colitis disease activity as subjectively assessed by patient-completed
      questionnaires following orthotopic liver transplantation for sclerosing
      cholangitis.
AB  - To assess whether or not liver transplantation and subsequent immunosuppression
      with cyclosporine and prednisone affect ulcerative colitis symptomatology, we
      surveyed by questionnaire all 23 surviving patients with pretransplant
      colonoscopy-documented ulcerative colitis who were transplanted for primary
      sclerosing cholangitis between June 1982 and September 1985. At follow-up [89.8
      +/- 7.6 weeks (mean +/- SEM], all six patients who had had asymptomatic
      colonoscopy-documented ulcerative colitis reported continued ulcerative colitis
      quiescence. Among the 17 patients who had had symptomatic colonoscopy-documented
      ulcerative colitis at time of liver transplantation, 88.2% reported improvement
      in overall ulcerative colitis severity (P less than 0.001), with significant
      improvement in the frequency of bowel movements reported by 100%, in crampy
      abdominal pain by 87.5%, in bowel urgency by 75%, in the occurrence of pus or
      mucus in stool by 87.5%, in the incidence of ulcerative colitis flares by 81.8%,
      and in the number of days unable to function normally due to ulcerative colitis
      symptoms by 78.6% (all at least P less than 0.01). These data demonstrate that
      ulcerative colitis symptom severity significantly improves following liver
      transplantation with immunosuppression with cyclosporine and prednisone.

PMID- 1995270
TI  - Effect of psyllium hydrophilic mucilloid on serum cholesterol in the elderly.
AB  - The effect of psyllium hydrophilic mucilloid (PHM) when used as a laxative and/or
      stool softener on serum cholesterol concentrations was examined in 176 ambulatory
      elderly participants attending a health screening program. The change in one-year
      serum cholesterol concentration in subjects using PHM was compared with the
      change in cholesterol in 741 participants who did not report the use of PHM.
      Serum cholesterol concentration decreased by 0.073 mmol/liter (2.82 mg/dl) in the
      treatment group compared with a decrease of 0.036 mmol/liter (1.39 mg/dl) in the
      control group. After adjusting for confounding factors, excluding psyllium dose,
      by using a multiple regression model there was no significant difference in the
      change in serum cholesterol concentration (P = 0.935). PHM dosage information was
      available for 158 participants. After adjusting for baseline serum cholesterol
      and confounding factors using multiple regression analysis, it was found that the
      dose of PHM administered was significantly correlated with the change in serum
      cholesterol (P = 0.0120). For every 1-g increase in daily PHM dose there was a
      0.022 mmol/liter (0.84 mg/dl) decrease in serum cholesterol concentration.

PMID- 1995271
TI  - Epidermal growth factor regulation of DNA synthesis in human colonic lamina
      propria lymphocytes.
AB  - Epidermal growth factor (EGF) is a potent growth factor for many tissues
      including the gastrointestinal tract. EGF is present in the gut lumen and is
      absorbed through the mucosa in the developing animals. In addition, EGF has been
      found to alter the immune system. In this study, we investigated the in vitro
      effect of EGF on normal colonic lamina propria lymphocyte DNA synthesis and
      ornithine decarboxylase activity. Human colonic lamina propria lymphocytes were
      isolated by collagenase-EDTA digestion. The effect of EGF on Con A-stimulated
      lymphocyte thymidine incorporation was tested. We observed that EGF suppressed
      DNA synthesis and ornithine decarboxylase (ODC) activity in lamina propria
      lymphocytes. EGF did not alter the time course of thymidine incorporation into
      LPL stimulated by the combination of phorbol 12,13-dibutyrate (PDB) and
      ionomycin. Our data suggest that (1) EGF suppresses DNA synthesis in human
      colonic lamina propria lymphocytes as well as ODC activity and (2) this
      inhibition may be mediated through protein kinase C or calcium flux. We postulate
      that EGF may have a role in modulating the human gut immune system.

PMID- 1995272
TI  - Usefulness of fecal alpha 1-antitrypsin clearance and fecal concentration as
      early indicator of postoperative asymptomatic recurrence in Crohn's disease.
AB  - The aim of this study was to evaluate in Crohn's disease the possible usefulness
      of alpha 1-antitrypsin clearance and fecal concentration in the early detection
      of postoperative asymptomatic recurrence. Eleven adult patients with small bowel
      Crohn's disease undergoing elective resection were enrolled in the study and
      prospectively followed for one year. Three, six, and 12 months after surgery the
      alpha 1-antitrypsin clearance and fecal concentration were measured, and the
      disease activity was assessed. All patients were free of active symptoms
      throughout the study. One year after surgery small bowel radiology was performed
      in all patients. Radiographic evidence of recurrent macroscopic disease was found
      in five of the 11 patients. Three months after surgery both alpha 1-antitrypsin
      clearance and fecal concentration were significantly lower (P less than 0.01)
      than before surgery. There was no difference at this time between patients with
      recurrence and those with no recurrence. In patients with recurrence both alpha 1
      antitrypsin clearance and fecal concentration significantly increased at six
      months in comparison with the values at three months (P less than 0.02). Both
      measurements were significantly higher at six and 12 months in this group of
      patients than in those with no recurrence and in normal controls (P less than
      0.01). At six and 12 months alpha 1-antitrypsin clearance was above the upper
      normal limit in all patients with recurrence. We conclude that fecal alpha 1
      antitrypsin clearance is a noninvasive, inexpensive, sensitive marker of
      asymptomatic recurrence in CD patients who are under regular supervision after
      surgery.

PMID- 1995274
TI  - Johanson-Blizzard syndrome. Progression of pancreatic involvement in adulthood.

PMID- 1995273
TI  - Endometriosis. An important condition in clinical gastroenterology.
AB  - Endometriosis, a condition defined by the presence of ectopic endometrium, is a
      disorder of increasing incidence and a significant cause of gastroenterologic
      distress in young women. Although clinical manifestations vary considerably
      depending upon the anatomic extent of disease, characteristic abdominal
      complaints and typical physical findings continue to be associated with
      misdiagnosis and delayed recognition of gastrointestinal involvement. The authors
      of this paper review the medical literature concerning endometriosis of the
      digestive tract--emphasizing modes of presentation, risk factors, diagnostic
      testing, complications, and therapy. Greater familiarity with the disease and
      heightened awareness of its sequellae are needed and prerequisite to improved
      medical management.

PMID- 1995276
TI  - Ampullary tumor caused by metastatic renal cell carcinoma.
AB  - In this paper we report the case of a renal cell carcinoma (RCC) metastatic to
      the ampullary region. The patient presented with severe anemia due to blood loss
      from the ampullary tumor 11 years after nephrectomy for the primary renal cancer.
      The diagnosis was established by means of endoscopy and biopsy.

PMID- 1995275
TI  - Severe hemorrhagic radiation proctitis advancing to gradual cessation with
      hyperbaric oxygen.
AB  - We report a case of a male patient suffering from a severe hemorrhagic radiation
      proctitis which gradually ceased with hyperbaric oxygen. We discuss the
      mechanisms of chronic radiation injury and the effect of the hyperbaric oxygen.
      This therapy is proposed as an alternative to surgical intervention for this
      abnormality.

PMID- 1995277
TI  - Duodenal-caval fistula.
AB  - Duodenal-caval fistula is a rare, often lethal disease that requires prompt
      diagnosis and surgical correction. A case of duodenal-caval fistula due to
      duodenal ulceration is presented and discussed.

PMID- 1995279
TI  - Issues in the care of infants and toddlers with insulin-dependent diabetes
      mellitus.
AB  - Infants and children in the preschool age group who have insulin-dependent
      diabetes mellitus present a unique set of problems to the health care provider
      and to their families. These management issues include difficulty in achieving
      maximal metabolic control; the limited ability of the child to communicate
      feelings and needs; a significant financial burden to many young families; and
      the increased family stress and altered psychodynamics seen in families with very
      young children with chronic illnesses. The lability of diet, exercise, emotions,
      and overall life-style seen in this age group exacerbates each of these problems
      markedly. This paper addresses the challenges that these children present;
      discusses the issues and controversies; and describes how the Diabetes Clinic at
      Michigan State University uses a combination of methodologies and disciplines to
      deal with these problem areas.

PMID- 1995278
TI  - Amyloidosis complicating inflammatory bowel disease.

PMID- 1995280
TI  - Iatrogenic brittle diabetes: the hold-the-insulin decision.
AB  - Modern diabetes management often involves multiple daily insulin injections
      (MDII) for individuals with insulin-dependent diabetes mellitus (IDDM). Such
      insulin regimens are increasingly composed of a larger percentage of regular
      insulin and a smaller percentage of intermediate- and long-acting insulin.
      Withholding insulin in these individuals may precipitate acute metabolic
      catastrophe and attendant ketosis or, even worse, frank diabetic ketoacidosis. A
      comprehensive understanding of normal glucose metabolism and the principles of
      MDII by all health care professionals both in and out of the hospital setting
      will foster improved metabolic control in the individual with IDDM, reduce health
      care costs, and have a positive effect on decreasing diabetic complications.

PMID- 1995281
TI  - A modified quality-of-life measure for youths: psychometric properties.
AB  - In the Diabetes Control and Complication Trial (DCCT), a Diabetes Quality of Life
      (DQOL) measure was developed to assess the psychosocial impact of intensified
      regimens. Its applicability for use with children and adolescents was limited by
      the exclusion criteria of the DCCT. In this study, the DQOL was modified for
      specific use in young diabetes populations. The result is an instrument composed
      of three intercorrelated scales--a Diabetes Life Satisfaction scale, a Disease
      Impact scale, and a Disease-Related Worries scale--with satisfactory levels of
      reliability. While the scale variances were independent of glycosylated
      hemoglobin values, they were related to adolescents' perception of their general
      health status. Self-perceived quality of life related to diabetes management is
      an important alternative outcome for diabetes education programs.

PMID- 1995282
TI  - Implementing a holistic approach to diabetes care.
AB  - The concept of case assignment is an important development in diabetes education
      because it encourages a problem-solving approach to care, including evaluation of
      education, which is the basis of accountability and autonomous professional
      practice. Furthermore, case assignment and holistic care of clients with diabetes
      is a model of professional practice that benefits clients, practitioners, and
      administrators. Case assignment encourages comprehensive and efficient use of
      human and administrative resources, and provides a foundation for professional
      development and practitioner autonomy. Effective implementation of holistic care
      requires a reassessment by health professionals of practice protocols and a
      reorganization of policy and procedures. The expansion of professional skills
      necessary for the introduction of a holistic approach will (a) break down
      traditional practice barriers, and (b) extend the professional knowledge of
      diabetes care practitioners. Case assignment for diabetes education and follow
      up, if extensively adopted, is a mechanism that could contribute to achieving
      recognition of diabetes educators as independent practitioners, recognition of
      diabetes education as a practice specialty, and reimbursement for private
      practitioners.

PMID- 1995284
TI  - Diabetes education: a worldwide challenge.

PMID- 1995283
TI  - Tips on preparing and submitting materials for the AADE scholarship award.

PMID- 1995285
TI  - Prevention of insulin leakage after subcutaneous injection.

PMID- 1995286
TI  - Diabetes instruction of the person with HIV infection.

PMID- 1995287
TI  - Estrogen-inducible progesterone receptor in primary cultures of rat glial cells.
AB  - The presence of an estrogen-inducible progesterone receptor was demonstrated in
      primary cultures of newborn rat glial cells by biochemical and
      immunohistochemical techniques. The progesterone receptor (PR) was measured 3-4
      weeks after primary culture in estradiol-containing or control medium. Cells were
      labeled with the synthetic progestin [3H]R5020 followed by ultracentrifugation
      analysis of the cellular extracts. A "9 S" PR was observed in the cytosol and a
      "4-5 S" PR was found in the nuclear high salt, tungstate ions containing extract
      of estradiol-treated cells. When the antiprogestin [3H]RU486 was used instead of
      [3H]R5020 as a ligand, a 9 S PR was also found in the cytosol, but a nonactivated
      "8.5 S" receptor complex was identified in the high salt nuclear fraction in
      presence of tungstate ions. The levels of PR, as measured by whole cell assay,
      were significantly increased when glial cells were cultured in the presence of 50
      nM estradiol, as compared to nonestradiol-treated controls. The estrogen
      induction of PR was suppressed by the antiestrogen tamoxifen, but tamoxifen by
      itself had no effect on PR concentration. When the glucocorticosteroid receptor
      and PR were measured in parallel after estradiol treatment of the same primary
      culture, only the levels of PR were increased. The PR was visualized inside glial
      cells by immunohistochemical studies with a monoclonal antibody specific for the
      B-form of PR (KC 146), which was recognized by fluorescein-linked or biotinylated
      secondary antibodies. Strong staining was observed in estradiol-treated cultures,
      when compared to a weaker staining in control cultures. This is the first
      demonstration of PR in rat glial cells, and we present evidence of its induction
      by estradiol in primary cultures.

PMID- 1995288
TI  - Reorganization of microfilaments in macrophages after LPS stimulation.
AB  - Lipopolysaccharide (LPS), a potent activating substance of macrophages, induced
      the reorganization of microfilaments in macrophages obtained from C3H/HeN mice.
      At 1 min after LPS addition, a slight disassembly of actin was observed. At 2 to
      4 min, there was a gradual assembly; then, at 5 and 6 min, a subsequent rapid
      disassembly occurred. We employed two methods to observe this process. One was
      the RITC-phalloidin staining of actin filaments and the other was the extraction
      of monomeric actin and unstable actin filaments with Triton X-100 solution. The
      results obtained by the two methods were basically in agreement. Nevertheless,
      there was a discrepancy between the results from the two methods, concerning the
      ratio of assembly and disassembly. The RITC-phalloidin staining was more
      sensitive in detecting actin assembly and less sensitive in detecting the
      disassembly than the extraction with Triton X-100 solution was. This difference
      suggests that some of the unstable filaments, which were extracted with Triton X
      100 solution and fixed with formalin, were formed during the LPS-induced
      reorganization process. This reversible actin assembly could not be observed in
      the LPS-nonresponder, C3H/HeJ mouse macrophages. We concluded that the observed
      process could be attributed to LPS-signal triggering pathways subsequent to LPS
      binding and that a necessary component to initiate effective LPS-signaling, which
      is probably deficient in C3H/HeJ mice, is involved in this reorganization process
      of LPS-stimulated macrophages.

PMID- 1995289
TI  - Desmoplakin expression and distribution in cultured rat bladder epithelial cells
      of varying tumorigenic potential.
AB  - The expression and distribution of the desmosomal plaque proteins, desmoplakins
      (DPs) I and II, were studied in nontumorigenic (RBE-8) and a series of
      tumorigenic (AY34, R-4909, SS-24B, RBTCC-8, and 804G) rat bladder epithelial cell
      lines. These cell lines ranged from slow-growing papillary transitional cells
      (AY34) to rapidly metastatic carcinoma cells (RBTCC-8). DPs I and II were shown
      by immunoblotting and Northern analysis to be present in nontumorigenic RBE-8
      cells as well as in all of the tumorigenic cell lines, albeit in differing
      amounts. Immunofluorescence microscopy revealed striking differences in DP
      distribution, corresponding in general with increases in tumorigenic potential.
      Whereas DPs of normal RBE-8 cells and less tumorigenic AY34 cells were localized
      predominantly at cell interfaces, the more tumorigenic lines exhibited a high
      proportion of DP in the form of cytoplasmic dots, a distribution reminiscent of
      that seen in epithelial cells maintained in low levels of extracellular calcium.
      In 804G cells, which represented the most extreme example of this phenomenon, the
      majority of DPs were organized as cytoplasmic dots. Electron microscopy revealed
      intermediate filament (IF)-associated spots in the cytoplasm as well as an
      elaborate array of IF-associated plaques at the cell-substratum interface. The IF
      associated spots in the cytoplasm reacted with anti-DP antibody in immunogold
      labeling experiments while those at the cell-substratum did not react. In more
      dense cultures of 804G cells, certain cells stratified and expressed increased
      amounts of DP followed by the induction of new keratins including those of the
      skin type. Decreasing extracellular calcium resulted in a rearrangement of DP in
      each cell line; staining at cell-cell interfaces disappeared and was replaced
      with a pattern of cytoplasmic dots. These results demonstrate a possible
      relationship between desmosome assembly and/or maintenance and tumorigenic
      potential.

PMID- 1995290
TI  - Identification of a brain-specific 27/26-kDa extracellular protein with the
      monoclonal antibody to differentiated PC12h pheochromocytoma cells.
AB  - We have searched for brain-specific extracellular molecules using a library of
      monoclonal antibodies against surface antigens of differentiated PC12h cells. One
      of the monoclonal antibodies, PCH42-14, recognized a 27/26-kDa protein of 10-week
      old rat brain on immunoblotting. PCH42-14 antigen was detected only in brain,
      especially in cerebrum, olfactory bulb, mesencephalon, hippocampus, medulla
      oblongata, and spinal cord. On hippocampal neuron culture, PCH42-14 antigen
      existed extracellularly along with the neuronal extensions.

PMID- 1995291
TI  - Collagen gel contraction by fibroblasts requires cellular fibronectin but not
      plasma fibronectin.
AB  - Fibroblasts embedded in three-dimensional lattices of collagen fibrils have been
      known to require serum constituents to induce a cell-mediated contraction of
      collagen gels. The gel contraction was studied with human skin fibroblasts
      cultured in the presence of fetal bovine serum (FBS). Removal of bovine serum
      fibronectin (sFN) from FBS did not affect the extent of gel contraction. Gel
      contraction occurred in serum-free defined media. Therefore, it is concluded that
      sFN is not required for gel contraction. That cellular FN (cFN) synthesized and
      secreted by fibroblasts plays a crucial role in gel contraction was suggested by
      the following experiments: (1) We obtained monoclonal antibodies (mAb A3A5)
      against fibroblast surface antigens, which suppressed the fibroblast-mediated gel
      contraction. Immunoblot analyses showed that mAb A3A5 recognizes cFN secreted by
      human fibroblasts and human plasma FN (pFN), but not bovine sFN in FBS used for
      culture. (2) Addition of rabbit antisera, which recognize human cFN, to a serum
      free gel culture inhibited contraction. Uninvolvement of human pFN in gel
      contraction was further confirmed by the fact that neither pretreatment of
      fibroblasts with excess amounts of human pFN nor the presence of excess amounts
      of human pFN in gels affected the extent of gel contraction. This study seems to
      be the first demonstration of functional difference between cFN and pFN (or sFN)
      and proposes a novel mode of binding of fibroblasts with collagen fibrils via cFN
      during cell-mediated collagen morphogenesis.

PMID- 1995292
TI  - Differential activation and inhibition of lymphocyte proliferation by modulators
      of protein kinase C: diacylglycerols, "rationally designed" activators and
      inhibitors of protein kinase C.
AB  - The tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA) can enhance or
      inhibit lymphocyte proliferation. Enhancement correlated with increased
      interleukin 2 (IL-2) production and activation of protein kinase C while
      inhibition correlated with decreased IL-2 and downregulation of protein kinase C
      activity (D.S. Grove and A.M. Mastro, Cancer Res. 51, 82-88). In this study,
      various activators and inhibitors of protein kinase C were used in order to try
      to separate the effects of TPA on this enzyme from its effects on IL-2 production
      and determine if protein kinase C activity was directly or indirectly related to
      IL-2 production. 1,2-Dioctanoylglycerol, 1-oleoyl-2-acetyl-glycerol,
      phospholipase C, and two "rationally designed" activators, 6-(N-decylamino)-4
      hydroxy-methylindole and 3-(N-acetylamino)-5-(N-decyl-N-methylamino)-benzyl
      alcohol, were tested. Some activators enhanced proliferation in the presence of a
      Ca2+ ionophore, ionomycin, but not concanavalin A. Some activators suppressed
      proliferation and downregulated protein kinase C. Others neither downregulated
      protein kinase C nor inhibited IL-2 production and proliferation. However,
      inhibition or downregulation of protein kinase C activity always correlated with
      decreased IL-2 and depressed proliferation. Thus, the evidence in this and the
      previous study suggests that activation of protein kinase C is directly related
      to IL-2 production in activated T cells.

PMID- 1995293
TI  - Rapid induction of type X collagen gene expression in cultured chick vertebral
      chondrocytes.
AB  - During endochondral ossification, small rapidly proliferating chondrocytes mature
      into flattened disc-shaped cells and then into large round hypertrophic cells.
      These morphological changes are accompanied by a decrease in the rate of cell
      proliferation. Type X collagen synthesis is initiated during chondrocyte
      maturation and reaches very high levels in the hypertrophic cells. We have
      analyzed type X collagen gene expression in chick embryo vertebral chondrocytes
      that were allowed to mature in monolayer culture and were then switched to
      suspension culture. The resuspended chondrocytes changed in shape from flat to
      round and decreased the proliferation rate as they do in vivo. These events were
      accompanied by a rapid, dramatic increase in type X collagen gene expression at
      the levels of transcription, steady-state mRNA and protein synthesis, as well as
      an increase in the number of cells producing type X collagen. The amount of type
      X collagen gene expression in resuspended chondrocytes was comparable to that in
      mineralizing cartilage in vivo. These results indicate that events accompanying
      the switch from monolayer to suspension culture (for example, the change from a
      flat to a round shape and/or the decrease in proliferation rate) may play a role
      in the induction of type X collagen gene expression during chondrocyte
      maturation. Thus we have developed an in vitro system that appears to mimic the
      events occurring during in vivo chondrocyte maturation. This in vitro model may
      provide an ideal system for further examination of the parameters regulating
      chondrocyte maturation and type X collagen gene expression.

PMID- 1995294
TI  - Stress relaxation of contracted collagen gels: disruption of actin filament
      bundles, release of cell surface fibronectin, and down-regulation of DNA and
      protein synthesis.
AB  - Relaxation of stressed collagen gels provides a model system uniquely suited to
      studying the regulation of cell morphology and biosynthetic function by tissue
      organization. Stress relaxation results in rapid, synchronous changes in cell
      morphology without enzymatic or other drug treatments, and makes possible an
      analysis of the initial cellular events associated with changes in tissue
      organization. During the first hour after stress relaxation, we observed
      transient hypercontraction of collagen gels and loss of collagen fibril
      organization as stress in the system dissipated. Morphological changes in the
      fibroblasts included retraction of pseudopodia, collapse of cytoplasmic actin
      filament bundles, and loss of cell surface fibronectin. Accompanying these
      morphological changes, we observed marked decreases in DNA and protein synthesis,
      especially of fibronectin and type I procollagens. These results show that
      changes in tissue organization can exert rapid and profound effects on the
      morphology and biosynthetic function of cells within the tissue.

PMID- 1995295
TI  - IL-1 beta-induced expression of PDGF-AA isoform in rabbit articular chondrocytes
      is modulated by TGF-beta 1.
AB  - Interleukin 1 beta (IL-1 beta) and platelet-derived growth factor (PDGF) induced
      proliferation in many cell types. Both peptides are released by activated
      macrophages and other cells in response to injury and are thought to play a
      crucial role in a number of pathological processes. We found that IL-1 beta
      stimulates proliferation of rabbit articular chondrocytes and induces synthesis
      and release of PDGF into their culture medium. This effect, which is time- and
      dose-dependent (0.05-5 ng/ml), is restricted to PDGF-AA, one of the three PDGF
      isoforms; IL-1 beta effect on PDGF is inhibited by actinomycin D and alpha
      amanitin, suggesting a transcriptional regulation of PDGF-A chain. IL-1 beta
      stimulates PDGF-AA synthesis also in the presence of indomethacin, a
      prostaglandin synthesis inhibitor. Transforming growth factor beta 1 (TGF-beta
      1), a dimeric polypeptide which displays multiple biological activities, inhibits
      in a dose-dependent manner (1-10 ng/ml) PDGF-AA production induced by IL-1 beta.
      In a binding assay, TGF-beta 1 induces 45% decrease in specific binding sites for
      125I-IL-1 beta, with no change in affinity.

PMID- 1995296
TI  - Behavior of a transitional tubulovesicular compartment at the cis side of the
      Golgi apparatus in in vivo fusion studies of mammalian cells.
AB  - We have investigated the behavior in in vivo cell fusion experiments of a
      transitional compartment lying between the endoplasmic reticulum and Golgi
      apparatus to determine if the compartment, as recognized by the antibody G1/93,
      might congregate in a similar manner to Golgi apparatus [W. C. Ho et al. (1990)
      Eur. J. Cell Biol. 52, 315-327]. The distributions of the transitional
      tubulovesicular compartment, endoplasmic reticulum, and Golgi apparatus in HeLa
      cells were assessed by immunofluorescent staining using mouse monoclonal antibody
      G1/93, mouse monoclonal antibody HP 24, and rabbit anti-galactosyltransferase,
      respectively. In agreement with previous results [W. C. Ho et al. (1990) Eur. J.
      Cell Biol. 52, 315-327], the Golgi apparatus was observed to congregate gradually
      over a 3- to 6-h period, forming a large, extended, central Golgi complex in uv
      inactivated Sindbis virus-fused HeLa cells. Concomitant with this was a marked
      congregation of the transitional tubulovesicular compartment. Congregation of the
      tubulovesicular compartment was not affected by cycloheximide. The endoplasmic
      reticulum retained its web-like distribution throughout the syncytoplasm and
      rimmed the nuclear periphery. Treatment of HeLa cells with nocodazole prior to
      fusion followed by incubation of the syncytia in drug-containing media blocked
      congregation of the G1/93-positive compartment. With this long-term nocodazole
      treatment, Golgi apparatus was dispersed into scattered Golgi elements and the
      G1/93 distribution was endoplasmic reticulum-like. These results suggest that the
      transitional tubulovesicular compartment recognized by G1/93 is normally
      structured on microtubules and microtubule organizing centers and may be
      considered to be a subcompartment of a greater, perinuclear, Golgi complex.

PMID- 1995297
TI  - Patterns of protein synthesis in various cells after extreme heat shock.
AB  - The analysis of proteins synthesized in rat thymocytes and mouse teratocarcinoma
      PCC-4 Aza 1 and myeloma Sp2/0 cells after 1 h of treatment at 42 or 44 degrees C
      was carried out. Shock at 42 degrees C reduced the total synthetic rate of
      proteins in all three cell lines and induced "classical" heat-shock protein with
      a mass of 70 kDa (hsp 70). Heat shock at 44 degrees C resulted in almost complete
      inhibition of protein synthesis; only a small amount of hsp 70 was synthesized.
      Meanwhile a new 48-kDa polypeptide (pI = 7.5) was found in the cells exposed to
      severe heat shock. This protein was compared by peptide mapping with other known
      polypeptides of the same size: heat-shock protein from chicken embryo cells and
      mitogen-stimulated polypeptide from human lymphoid cells. The peptide maps were
      not identical. It was also shown that after a shock at 44 degrees C
      teratocarcinoma cells were able to accumulate anomalous amounts of hsp 70 despite
      hsp 70 synthesis inhibition. The data show that reaction of various cells to
      extreme heat shock depends heavily on cell type.

PMID- 1995298
TI  - Production of platelet-like particles by a human megakaryoblastic leukemia cell
      line (MEG-01).
AB  - The distribution of microtubules and platelet-specific glycoproteins (GPIIb/IIIa)
      in particles was probed by an immunofluorescence method using anti-tubulin and
      anti-GPIIb/IIIa antibodies to identify whether particles released from a human
      megakaryoblastic cell line (MEG-01) are platelets. The fluorescence image showing
      anti-tubulin staining of the particles revealed a characteristic ring structure
      observed in platelets. Anti-platelet GPIIb/IIIa antibody staining showed an image
      in which small patches or spots were seen throughout the particle with brighter
      staining at the periphery. No significant difference was observed between these
      particles and human blood platelets under immunofluorescent staining. These
      results show that MEG-01 cells released platelet-like particles.

PMID- 1995299
TI  - In vitro attachment of skeletal muscle fibers to a collagen gel duplicates the
      structure of the myotendinous junction.
AB  - The myotendinous junction (MTJ) and its associated cells and connective tissue
      are important structures involved in transmission of contractile force from
      skeletal muscle to tendon. A model culture system was developed to investigate
      the formation of the MTJ and its attachment to collagen fibers. Skeletal muscle
      cells were cultured in a well modeled from two layers of a native gel of type I
      collagen. Muscle cells cultured in this manner formed attachments to the collagen
      gel and developed into highly contractile multinucleated muscle fibers with the
      development of extensive terminal invaginations of the sarcolemma. In addition,
      the subsarcolemma at the ends of muscle fibers showed areas of increased electron
      density which corresponded well with the termini of myofibrils. The results
      indicate that the development of sarcolemmal invaginations at the end of a muscle
      fiber probably occurs intrinsically during muscle development in vivo. The direct
      association of collagen fibers with the basal lamina at the end of muscle fibers
      was only occasionally observed in culture, suggesting that other fibrils or
      proteins may also be involved in the attachment of collagen fibers to the basal
      lamina of muscle fibers at the MTJ.

PMID- 1995300
TI  - The S-phase cytotoxicity of camptothecin.
AB  - The DNA topoisomerase I inhibitor camptothecin (CAM) is selectively cytotoxic to
      S-phase cells of HL-60, and some other myelogenous leukemic lines. The early
      effects of cell exposure to 0.05-0.2 micrograms/ml CAM are seen after 2 h; at
      that time a progressive degradation of DNA in the chromatin of S-phase cells is
      initiated. The degradation manifests by "pulverization" of chromatin followed by
      coalescence of the fine granules and nuclear disintegration. Between 2 and 6 h of
      treatment, a loss of about 30-70% of DNA from S-phase nuclei is detected by flow
      cytometry. A 10-min pulse of CAM is adequate to trigger subsequent DNA
      degradation. Agarose gel electrophoresis of DNA from CAM-treated cells reveals a
      typical nucleosome core particles "ladder," suggestive of preferential
      degradation of spacer DNA. Despite extensive loss of DNA and nuclear
      disintegration, the cell membrane of CAM-treated S-phase cells remains intact for
      several hours, excluding trypan blue or propidium iodide. Mitochondria, assayed
      for their ability to maintain a transmembrane potential (rhodamine 123
      retention), as well as the lysosomal proton pump (probed by supravital uptake of
      acridine orange) also remain unchanged in these cells. G1 cells are refractory to
      CAM under these conditions. Synchronization of cells in S phase by aphidicolin
      increases the sensitivity of the whole cell population to CAM. The data suggest
      that CAM or other topoisomerase I inhibitors may be effective in some myelogenous
      leukemias, especially in combination with treatments synchronizing cells in S
      phase.

PMID- 1995301
TI  - Introduction of new genetic markers on human chromosomes.
AB  - The purpose of this study was to use DNA transfection and microcell chromosome
      transfer techniques to engineer a human chromosome containing multiple
      biochemical markers for which selectable growth conditions exist. The starting
      chromosome was a t(X;3)(3pter----3p12::Xq26----Xpter) chromosome from a
      reciprocal translocation in the normal human fibroblast cell line GM0439. This
      chromosome was transferred to a HPRT (hypoxanthine phosphoribosyltransferase)
      deficient mouse A9 cell line by microcell fusion and selected under growth
      conditions (HAT medium) for the HPRT gene on the human t(X;3) chromosome. A
      resultant HAT-resistant cell line (A9(GM0439)-1) contained a single human t(X;3)
      chromosome. In order to introduce a second selectable genetic marker to the
      t(X;3) chromosome, A9(GM0439)-1 cells were transfected with pcDneo plasmid DNA.
      Colonies resistant to both G418 and HAT medium (G418r/HATr) were selected. To
      obtain A9 cells that contained a t(X;3) chromosome with an integrated neo gene,
      the microcell transfer step was repeated and doubly resistant cells were
      selected. G418r/HATr colonies arose at a frequently of 0.09 to 0.23 x 10(-6) per
      recipient cell. Of seven primary microcell hybrid clones, four yielded G418r/HATr
      clones at a detectable frequency (0.09 to 3.4 x 10(-6)) after a second round of
      microcell transfer. Doubly resistant cells were not observed after microcell
      chromosome transfers from three clones, presumably because the markers were on
      different chromosomes. The secondary G418r/HATr microcell hybrids contained at
      least one copy of the human t(X;3) chromosome and in situ hybridization with one
      of these clones confirmed the presence of a neo-tagged t(X;3) human chromosome.
      These results demonstrate that microcell chromosome transfer can be used to
      select chromosomes containing multiple markers.

PMID- 1995302
TI  - A novel 43-kDa glycoprotein is detected in the nucleus of mammalian cells by
      autoantibodies from dogs with autoimmune disorders.
AB  - We have characterized a new antibody specificity in a panel of sera from dogs
      developing systemic lupus erythematosus (SLE) or clinically related autoimmune
      disorders. This antibody stains in a speckled fashion the nucleus of cells of
      different mammalian origins. The target antigen is a basic (pI 9.2) nuclear
      polypeptide with an apparent molecular weight of 43 kDa (p43) which is detected
      in various mammalian cell nuclei. p43, as studied in HeLa cells, appears to be
      cell cycle-independent. It is released from nuclei by salts (0.5 M NaCl or 0.25 M
      ammonium sulfate). Upon subfractionation of nuclear components, p43 is found in
      the fraction containing HnRNPs and is recovered in immunoprecipitates obtained
      with 4F4 monoclonal antibody to HnRNP C proteins. Immunoelectron microscopy
      revealed that p43 is concentrated over the dense chromatin periphery and
      interchromatin granule clusters. Another important feature of p43 is its ability
      to specifically bind wheat germ agglutinin lectin but not concanavalin A nor Ulex
      europaeus I, supporting the notion that p43 is a glycoprotein bearing an N-acetyl
      glucosamine moiety. Consistent with this result, a radio-active p43 band is
      specifically immunoprecipitated by canine anti-p43 autoantibodies from HeLa cells
      metabolically labeled with [14C]glucosamine. Finally, anti-p43 antibodies do not
      immunoprecipitate SnRNA, indicating that p43 has no apparent association with
      SnRNPs.

PMID- 1995303
TI  - Transport of Balbiani ring granules through nuclear pores in Chironomus tentans.
AB  - Balbiani ring granules are premessenger RNP particles synthesized in the larval
      salivary glands of the dipteran Chironomus tentans and containing the genetic
      information for large-sized secretory proteins. The granules in the nucleoplasm
      consist of a thin elementary RNP fiber tightly packed into an RNP ribbon, which
      is bent into a ring-like shape. When the 50-nm granule is translocated through
      the nuclear pore, it attains an elongated conformation. We have now demonstrated
      that the particle in transition can be described as an RNP ribbon with the same
      thickness and the same minimal width as the ribbon of the nucleoplasmic granules.
      The ribbon in the pore is, however, somewhat longer and it lacks the broad
      regions of the ribbon in the nucleoplasmic granule. We conclude that when
      entering the pore the bent ribbon of the Balbiani ring granule is being
      straightened and also somewhat drawn out, while its width is accommodated to the
      maximal size of the pore, i.e., about 25 nm. On the cytoplasmic side the ribbon
      is unpacked, and the elementary fiber can be seen extending into cytoplasm,
      probably being available for polysome assembly.

PMID- 1995305
TI  - Induction of extracellular matrix gene expression in normal human keratinocytes
      by transforming growth factor beta is altered by cellular differentiation.
AB  - Changes in epithelial substrate have been related to the cellular capacity for
      proliferation and to changes in cellular behavior. The effect of TGF beta 1 on
      the expression of the basement membrane genes, fibronectin, laminin B1, and
      collagen alpha 1 (IV), was examined. Northern analysis revealed that treatment of
      normal human epidermal keratinocytes with 100 pM TGF beta 1 increased the
      expression of each extracellular matrix (ECM) gene within 4 h of treatment.
      Maximal induction was reached within 24 h after treatment. The induction of ECM
      mRNA expression was dose dependent and was observed at doses as low as 1-3 pM TGF
      beta 1. Incremental doses of TGF beta 1 also increased cellular levels of
      fibronectin protein in undifferentiated keratinocytes and resulted in increased
      secretion of fibronectin. Squamous-differentiated cultures of keratinocytes
      expressed lower levels of the extracellular matrix RNAs than did undifferentiated
      cells. Treatment of these differentiated cells with TGF beta 1 induced the
      expression of fibronectin mRNA to levels seen in TGF beta-treated,
      undifferentiated keratinocytes but only marginally increased the expression of
      collagen alpha 1 (IV) and laminin B1 mRNA. The increased fibronectin mRNA
      expression in the differentiated keratinocytes was also reflected by increased
      accumulation of cellular and secreted fibronectin protein. The inclusion of
      cycloheximide in the protocol indicated that TGF beta induction of collagen alpha
      1 (IV) mRNA was signaled by proteins already present in the cells but that TGF
      beta required the synthesis of a protein(s) to fully induce expression of
      fibronectin and laminin B1 mRNA. The differential regulation of these genes in
      differentiated cells may be important to TGF beta action in regulating
      reepithelialization.

PMID- 1995304
TI  - Quantitative determination of rDNA transcription units in vertebrate cells.
AB  - The adenosine analogue 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB)
      unravels the compact nucleoli to necklace-like structures when applied to living
      cells. The nucleolar beads contain RNA polymerase I (RPI) and argyrophilic
      proteins, both properties considered to be characteristic of ribosomal gene
      activity. Each granule is supposed to represent a single transcription unit
      consisting of an actively transcribing gene and its RPI complex. Indirect
      immunofluorescence with anti-RPI antibodies was used to determine the number of
      transcription units in DRB-treated cells of some representative mammals,
      marsupials, birds, and amphibians. We estimate that 45 to 145 rRNA genes are
      transcriptionally active in vertebrate fibroblasts, depending on the species.
      Nucleolar transcriptional activity does not correlate with the total number of
      rRNA genes. During in vitro aging of fibroblasts, the number of transcription
      units appears to remain unchanged. Different cell types of one same organism show
      varying numbers of transcription units, reflecting their differential metabolic
      activity. A particular situation exists in phytohemagglutinin-stimulated
      lymphocytes. In the course of nucleolar activation, the number of transcription
      units is increased considerably, implying that formerly inactive rRNA genes are
      recruited for transcription. The opposite phenomenon is observed during
      spermatogenesis. With the diploid spermatocytes developing into haploid
      spermatids, the transcriptionally active rRNA genes decrease in number until rRNA
      synthesis is completely blocked.

PMID- 1995306
TI  - Alpha-interferon reduces in vivo phosphorylation of P210bcr/abl protein during
      hemin-induced erythroid differentiation of K-562 cells.
AB  - alpha-Interferon (IFN-alpha) is important in the management of chronic
      myelogenous leukemia (CML). The P210bcr/abl fusion protein, with enhanced
      tyrosine kinase activity, is implicated in the pathogenesis and progression of
      the disease. To elucidate the inhibitory mechanism of IFN-alpha on CML cell
      proliferation, we studied the effect of IFN-alpha on P210bcr/abl in K-562 cells.
      The phosphorylated level of P210bcr/abl was not altered by treatment with IFN
      alpha alone despite its inhibiting cell proliferation. However, when K-562 cells
      were treated with either a low (5 x 10(2) U/ml) or high (10(4) U/ml)
      concentration of IFN-alpha in the presence of hemin, P210bcr/abl protein activity
      decreased through reduction of in vivo phosphorylation, but not through
      inhibition of de novo protein synthesis. Furthermore, hemoglobin content was
      increased by IFN-alpha at both low and high concentrations in tandem with hemin
      induced erythroid differentiation and the change in P210bcr/abl. These results
      demonstrate that IFN-alpha synergises hemin-mediated erythroid differentiation as
      it reduces the in vivo tyrosine phosphorylation of P210bcr/abl in K-562 cells.

PMID- 1995307
TI  - A mouse endothelial cell-specific monoclonal antibody: its reactivity with LTMC
      endothelium.
AB  - The binding of a marrow cell-related monoclonal antibody (H513E3 MAb) has been
      investigated in long-term marrow cultures (LTMC) and in vivo. Immunogold labeling
      and electron microscopy revealed that this antibody labeled an endothelial-like
      cell. Cross-reaction of anti-human Factor VIII confirmed endothelial specificity
      of the H513E3 MAb. In addition, vessel endothelium (vena cava, aorta, and marrow)
      exhibited binding of the antibody. This antibody provides a unique tool to study
      the cellular architecture of LTMC and implicates endothelium as an important
      component of LTMC. The function of the endothelial cell-specific surface antigen
      is unknown, although preferential labeling of the upper surface of endothelial
      cells suggests that it may play a role in cell communication, particularly with
      the floating population. The H513E3 MAb reacts with an external membrane antigen,
      a property that makes this antibody particularly useful for fluorescences
      activated sorting of endothelial cells.

PMID- 1995308
TI  - Immortalized fibroblastoid cells of osteopetrotic mutant mice (op/op) do not
      secrete CSF-1 and do not inhibit CSF-1 activity released by normal cells.
AB  - Osteopetrotic mutant mice (op/op) are deficient in osteoclasts and macrophages.
      In this report, the establishment of clonal permanent fibroblastoid cell lines
      from spleens of op/+ and op/op mice is described and conditioned medium obtained
      from these cell lines examined for release of growth factor that stimulates the
      proliferation and differentiation of macrophage precursor cells. It is shown that
      conditioned medium of op/+ fibroblastoid cells contains CSF-1 activity, whereas
      conditioned medium of op/op fibroblastoid cells does not. Conditioned medium of
      op/op cell lines does not inhibit colony-stimulating factor 1 (CSF-1) activity in
      conditioned medium of op/+ cells. Hybrids between op/op and op/+ fibroblastoid
      cells release CSF-1 activity in amounts similar to op/+ cell lines alone. These
      results confirm that op/op mice do not produce any CSF-1 activity. The data
      further suggest that predicted truncated proteins expressed from the mutated CSF
      1 gene in op/op mice are functionally not relevant and that there is no evidence
      for trans-acting factors in op/op that might inhibit CSF-1 expression.

PMID- 1995309
TI  - The resolution, enrichment, and organization of normal bone marrow high
      proliferative potential colony-forming cell subsets on the basis of rhodamine-123
      fluorescence.
AB  - Cell sorting on the basis of rhodamine-123 (Rh123) fluorescence has been used in
      conjunction with negative immunomagnetic selection to analyze the high
      proliferative potential colony-forming cell (HPP-CFC) compartment of normal
      murine bone marrow and to resolve and enrich HPP-CFC subpopulations responsive to
      different combinations of the hemopoietic growth factors interleukin 1 alpha (IL
      1 alpha), interleukin-3 (IL-3), and colony-stimulating factor 1 (CSF-1). HPP-CFC
      with a specific requirement for IL-1 alpha plus IL-3 plus CSF-1 in order to
      proliferate were resolved and enriched on the basis of their low Rh123 retention
      (Rh-dull), whereas HPP-CFC that grew in the presence of IL-3 plus CSF-1, IL-3
      alone, or CSF-1 alone were Rh-bright. Further addition of IL-1 alpha to IL-3 plus
      CSF-1 stimulated few additional HPP-CFC in the Rh-bright fraction. Our data
      confirm the value of Rh123 as a probe for the dissection and analysis of the
      primitive hemopoietic stem cell (PHSC) compartment. These data also show that the
      Rh123 staining characteristics of IL-1 alpha plus IL-3 plus CSF-1-responsive HPP
      CFC are consistent with the hypothesis that these HPP-CFC are closely related to
      PHSC with long-term reconstituting capacity in vivo and that they are among the
      most primitive progenitors yet detected in clonal agar culture.

PMID- 1995310
TI  - GM-CSF therapy for delayed engraftment after autologous bone marrow
      transplantation.
AB  - Based on previous observations that granulocyte-macrophage colony-stimulating
      factor (GM-CSF) promotes granulocyte recovery following chemotherapy, we
      evaluated the effect of recombinant human GM-CSF on hematopoietic progenitors and
      clinical outcome in six patients with delayed engraftment (greater than 55 days)
      after high-dose therapy and autologous bone marrow transplantation (ABMT). Three
      patients responded to a 14-day course of GM-CSF (10 micrograms/kg body
      weight/day) with at least a sevenfold rise in circulating granulocytes and a
      corresponding increase in granulopoietic activity in the bone marrow. A fourth
      patient died of infection on the 8th day of GM-CSF therapy with no evidence of
      response, and the remaining two, one of whom received a lower dose of GM-CSF (5
      micrograms/kg/day), did not respond. There was no change in platelet or red cell
      transfusion requirements in any patient during the treatment. In two of the three
      responders, the granulocyte counts returned to pretreatment levels by 4 and 7
      weeks after stopping the drug, respectively. We observed a marked increase in
      marrow-derived as well as in circulating granulocyte-macrophage progenitors
      (granulocyte-macrophage colony-forming units, CFU-GM) by the end of the 14-day
      course of GM-CSF in the three responders. There was no change in the frequency of
      circulating or marrow-derived erythroid (erythroid burst-forming units, BFU-E) or
      multilineage (multilineage colony-forming units, CFU-GEMM) progenitors. The
      results indicate that GM-CSF therapy in patients with markedly delayed
      engraftment after ABMT may stimulate granulopoiesis, but the effect is transient
      in some patients.

PMID- 1995311
TI  - Effect of low frequency low energy pulsing electromagnetic fields on mice
      injected with cyclophosphamide.
AB  - C3H mice have been used to investigate the effect of a combination of
      cyclophosphamide (CY) and electromagnetic fields (PEMF). Mice were injected i.p.
      with a single dose of 200 mg/kg body weight of CY and then exposed to PEMF 24 h
      per day. In an initial series of experiments immediately after CY injection mice
      were exposed to PEMF until sacrifice. WBC counts in the peripheral blood
      demonstrated a quicker decline in WBC at days 1 and 2 in mice exposed to PEMF.
      Groups of mice were sacrificed at days 1, 4, 6, 8, and 10 after CY injection. In
      mice exposed to PEMF the spleen weight was less than in controls at days 6, 8,
      and 10. Autoradiographic studies demonstrated that the labeling index of bone
      marrow smears did not significantly differ between controls and experimental mice
      exposed to PEMF, whereas the spleen labeling index proved to be higher among
      control mice versus mice exposed to PEMF at day 6, and higher among mice exposed
      to PEMF versus controls at day 8. In a second series of experiments mice were
      exposed to PEMF only over the 24 h following CY injection. We found that the
      spleens of mice exposed to PEMF weighed less than those of controls at days 6 and
      8. The labeling index of bone marrow did evidence a slight decrease among mice
      exposed to PEMF at days 8 and 10 after CY injection versus control mice. The
      spleen labeling index proved to be lower in experimental mice exposed to PEMF
      than in controls at days 4, 6, and 8. Mice were then injected with CY, half were
      exposed to PEMF, and 24 h later bone marrow was recovered from both groups of
      animals. The same number of bone marrow cells was injected via the tail vein into
      recipient mice irradiated to 8.5 Gy. The grafting efficiency of the bone marrow
      was evaluated by examining the number of spleen colonies and the spleen and bone
      marrow labeling indices at day 8; all parameters proved to be significantly lower
      among mice grafted with the bone marrow of mice injected with CY and exposed to
      PEMF than among controls injected with CY only. Finally, we found th at the
      effect of PEMF is evident only if mice are exposed during the 24 h following CY
      injection. The data reported here indicates that PEMF exposure after CY injection
      increases the damage induced in mice by CY.

PMID- 1995312
TI  - Analysis of granulocyte-macrophage colony-stimulating factor action in
      differentiating myeloid leukemia cells: treatment with DMSO may reveal a common
      pathway for growth factor gene regulation.
AB  - Previous studies showed that factor-independent, late-passage HL60 acute
      nonlymphocytic leukemia (ANLL) cells proliferated in response to granulocyte
      macrophage colony-stimulating factor (GM-CSF) after treatment with
      dimethylsulfoxide (DMSO) or other agents inducing cellular differentiation. In
      the present studies, we examined mechanisms of this response. After treatment
      with DMSO, GM-CSF delayed expression of some HL60 differentiation programs (CD11b
      expression), but not others (nitro blue tetrazolium dye reduction), and delayed
      the exit of cells from the cell cycle. In the presence of DMSO, GM-CSF but not
      granulocyte colony-stimulating factor (G-CSF) increased expression of steady
      state c-myc RNA. DMSO-treated HL60 cells expressing heterologous epidermal growth
      factor (EGF) receptors also proliferated in response to EGF and showed increased
      c-myc expression. Nuclear transcription studies showed that GM-CSF did not alter
      c-myc transcription in DMSO-treated cells, and studies using actinomycin-D showed
      no increase in steady-state c-myc RNA half-life. These studies indicate that GM
      CSF increases post-deterministic proliferation and alters the phenotype of
      differentiating HL60 cells, and post-transcriptional alterations in c-myc
      expression may be responsible for some of these changes. Heterologous EGF
      receptors mediate similar responses, suggesting that treating HL60 cells with
      DMSO may reveal a common pathway of growth factor gene regulation.

PMID- 1995314
TI  - Direct morphological evidence of high-dose methylprednisolone-induced maturation
      of leukemic cells in children with acute nonlymphoblastic leukemia.

PMID- 1995313
TI  - Acute lymphoblastic leukemia blast cells do not inhibit bone marrow hematopoietic
      progenitor colony formation.
AB  - In newly diagnosed patients with acute lymphoblastic leukemia (ALL), bone marrow
      (BM) morphology always shows "replacement" by blasts with decreased or absent
      normal hematopoietic elements. To answer the question of whether ALL blasts
      inhibit replication and maturation of normal marrow progenitors, we studied the
      interaction of normal marrow with BM specimens from 16 new cases of ALL.
      Irradiated ALL blasts, supernatant derived from ALL blasts in suspension
      cultures, and conditioned medium prepared from ALL blasts augmented the colony
      forming ability of normal marrow erythroid burst-forming unit (BFU-E),
      granulocyte-macrophage colony-forming unit (CFU-GM), megakaryocyte colony-forming
      unit (CFU-MK), and multilineage colony-forming unit (CFU-GEMM) progenitors. In
      sharp contrast to published data on the suppressive effects of acute myeloblastic
      leukemia cells on normal hematopoiesis in vitro, our results indicate that the
      growth advantage of ALL cells over normal marrow elements is not mediated through
      an inhibitory mechanism derived from leukemia cells.

PMID- 1995315
TI  - An ibuprofen-antagonized plasmin inhibitor released by human endothelial cells.
AB  - Serum-free culture medium harvested from endothelial cell monolayer cultures
      derived from human scars and dermis was examined for inhibition of fibrinolysis
      using a fibrin plate assay. Human cultured fibroblasts and smooth muscle cells
      did not produce any detectable inhibitory activity. The inhibitor is
      spontaneously released from the cultured endothelial cells over time. In the
      fibrin plate assay of plasmin-induced fibrinolysis, one nonsteroidal
      antiinflammatory (NSAI) drug, ibuprofen, was demonstrated to antagonize the
      inhibition of fibrinolysis. The antagonistic activity of ibuprofen appears
      unrelated to its NSAI drug activity because other NSAI drugs such as indomethacin
      and tolmetin have minimal antagonistic activity. Heating the cultured endothelial
      cells to 42 degrees C stimulates greater release of the inhibitor in a shorter
      period of time. This plasmin inhibitor, which is produced by endothelial cells,
      may contribute to postburn vascular occlusion, leading to secondary progressive
      necrosis in burn-traumatized patients.

PMID- 1995316
TI  - Autometallographic localization of inorganic mercury in the kidneys of rats:
      effect of unilateral nephrectomy and compensatory renal growth.
AB  - The histochemical technique of autometallography was used in the present study to
      demonstrate the zonal and tubular localization of inorganic mercury in the
      kidneys of unilaterally nephrectomized (NPX) and sham-operated (SO) rats given
      either a nontoxic 0.5 mumol/kg or a toxic 2.5 mumol/kg dose of mercuric chloride
      10 days after surgery. Deposits were found in the cortex and outer stripe of the
      outer medulla in both groups of rats given either dose of mercuric chloride. The
      deposits were localized exclusively in the convoluted and straight portion of the
      proximal tubule. Forty eight hours after the administration of the 0.5 mumol/kg
      dose of mercuric chloride, there were significantly more deposits in the renal
      outer stripe of the NPX rats than in the renal outer stripe of the SO rats. The
      number of deposits in the renal outer stripe of the NPX and SO rats given the 2.5
      mumol/kg dose of mercuric chloride was similar after 24 hr, but was greater than
      the corresponding rats given the nontoxic dose. These findings suggest that the
      proximal tubule (particularly the pars recta) is the primary site for the
      accumulation of inorganic mercury in the kidney. They also suggest that, in the
      rat, there is enhanced accumulation of inorganic mercury in the pars recta of
      proximal tubules in the outer stripe of the renal outer medulla when a nontoxic
      dose of inorganic mercury is given after unilateral nephrectomy or when a toxic
      dose of mercuric chloride is administered.

PMID- 1995317
TI  - Lipids in cells of atherosclerotic and uninvolved human aorta. III. Lipid
      distribution in intimal sublayers.
AB  - The distribution, content, and composition of tissue and cellular lipids in
      intimal layers of unaffected and atherosclerotic human aorta were studied. Aortic
      tissue was divided into medial and intimal layers; the intimal layer was further
      separated into elastic-hyperplastic and musculo-elastic sublayers. Cells were
      isolated from both intimal layers by enzyme digestion. The lipids extracted from
      whole tissue and cells were separated by TLC and analyzed by scanning
      densitometry. The highest content of phospholipids (PhL), triglycerides (TG),
      cholesterol (C), and cholesteryl esters (CE) was detected in the elastic
      hyperplastic layer of atherosclerotic plaque. However, taking into account that
      the elastic-hyperplastic layer of intima in lesioned areas was thickened, the
      lipid content per volume unit of both sublayers in fatty streaks and in plaques
      was equal. In the media underlying an atherosclerotic plaque, an increase in CE
      rather than in other lipid classes occurred. In the intima, an overall increase
      in PhL, TG, C, and CE content was found to display a constant ratio between these
      lipid classes, similar to that of low density lipoproteins (LDL). Cells isolated
      from atherosclerotic lesions had a higher lipid content than cells from areas of
      unaffected intima. However, the increase in the content of different lipid
      classes was not proportional, compared with tissue lipids. The content of PhL was
      the same, while an increase in TG, C, and CE was observed. The major contribution
      to excess cellular lipid accumulation in cells from atherosclerotic lesions was
      made by CE.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1995318
TI  - The pathogenesis of hyaline globules in liver cells after partial hepatectomy in
      rats.
AB  - To clarify the pathogenesis of hyaline globules in liver cells after partial
      hepatectomy, the present study was undertaken in rats. When partial hepatectomy
      was performed by the surgical procedure of Higgins and Anderson, the inferior
      vena cava pressure was raised, and many hyaline globules, which are very similar
      to those caused by condensation of the contents of vacuoles in liver cells after
      temporary pressure elevation of the inferior vena cava, were induced in liver
      cells. On the other hand, when the median lobe and the left lateral lobe were
      removed carefully one at a time to avoid operative narrowing of the inferior vena
      cava, the inferior vena cava pressure was not elevated, and only very few hyaline
      globules were formed. This suggests that hyaline globules in liver cells
      following partial hepatectomy in rats may be caused by elevation of inferior vena
      cava pressure due to narrowing of the inferior vena cava by surgical procedure.

PMID- 1995319
TI  - Thymic tumors induced by 3-methylcholanthrene treatment of rat Peyer's patches.
AB  - Studies were performed to characterize thymic tumors which were induced after a
      single injection of 500 microgram or 3-methylcholanthrene (3-MC) into surgically
      exposed Peyer's patches (PP) of Copenhagen rats. Detailed gross, histological,
      and morphological analyses revealed thymic tumors differing in size and weight (1
      to greater than 8 g) with distorted architecture and infiltration by lymphocytes
      and epithelial cells in varying proportions. Approximately 25% of the rats with
      thymic tumors exhibited abnormal spleens, whereas 66% developed low grade
      leukemias. A majority of the thymic tumors contained cells which exhibited (1)
      phenotypic markers characteristic of normal thymocytes, (2) abnormal DNA, and (3)
      increased percentages in S + G2 phases of the cell cycle. Further studies of
      tumor cell isolates demonstrated an increased frequency of colony formation on
      soft agar, as well as the ability to elicit thymic tumors upon transplantation.
      Collectively these studies describe chemically induced thymic lymphomas.

PMID- 1995320
TI  - Macrophage degradation of LDL extracted from human aortic plaques: effect of
      isolation conditions.
AB  - Several laboratories have recently reported on the structural and functional
      characteristics of an LDL fraction isolated from atherosclerotic lesions,
      designated A-LDL. Given the wide variety of tissue sources and isolation
      conditions that have been employed, we have addressed whether several procedures
      currently used affect the interaction of A-LDL with macrophages, and, if so, by
      what mechanisms. We isolated A-LDL from human aortic plaques by
      ultracentrifugation and gel filtration chromatography. Although some differences
      in the chromatographic elution profiles on gel filtration were apparent between
      homogenized and nonhomogenized extracts, A-LDL isolated from the same pool of
      plaque minces with or without homogenization showed no differences in macrophage
      degradation or inhibition of this degradation by excess acetyl-LDL. A-LDL
      isolated from plaques obtained at surgery or at autopsy less than 12 hr after
      death also showed no major differences in macrophage recognition, suggesting that
      post-mortem changes were probably not affecting cell recognition. However, A-LDL
      particles underwent aggregation when subjected to concentration, when stored for
      periods of 2 weeks or more, or when subjected to vortexing. The aggregated A-LDL
      was degraded more readily by macrophages than unaggregated A-LDL, and inhibition
      of degradation of aggregated A-LDL by excess acetyl-LDL was less than for
      unaggregated A-LDL. Collectively, these studies show that although post-mortem
      changes and tissue homogenization do not appreciably affect the interaction of A
      LDL with macrophages in culture, other isolation and preparation conditions have
      dramatic effects which could explain some of the diversity of A-LDL metabolism
      reported in the literature.

PMID- 1995321
TI  - Influences of antiplatelet autoantibodies on platelet function in immune
      thrombocytopenic purpura.
AB  - We investigated the characteristics of the antiplatelet autoantibodies in 60
      patients with ITP. Using flow cytometry, the binding of monoclonal antibodies to
      the platelet glycoprotein (GP) IIb/IIIa complex and to GPIb was examined in these
      patients. The extent of binding was decreased in 15 patients (anti-GPIIb/IIIa in
      12 patients and both anti-GPIIb/IIIa and anti-GPIb in 3 patients). Western
      blotting revealed that 10 of these 15 patients had either anti-GPIIb or anti
      GPIIIa and 2 had anti-GPIb autoantibodies, ADP-induced aggregation of normal
      platelets was inhibited by autoantibodies in 12 of 60 patients, and 11 of these
      had anti-GPIIb/IIIa antibodies. Ristocetin-induced aggregation was inhibited in 4
      of these patients, and 2 with prominent inhibition had anti-GPIb antibodies.
      There was a significant relationship between platelet-associated IgG value and
      ATP secretion. These results suggest that some antiplatelet autoantibodies can
      affect platelet function and thus have an influence on the pathophysiology of
      ITP.

PMID- 1995322
TI  - Monocytopenia and infections in chronic lymphocytic leukemia (CLL)

PMID- 1995323
TI  - Flow cytometric monitoring of parasitaemia during treatment of severe malaria by
      exchange transfusion.

PMID- 1995324
TI  - Salvage therapy with PROMACE in relapsed non-Hodgkin malignant lymphoma.

PMID- 1995325
TI  - Munchausen AIDS and haemophilia.

PMID- 1995326
TI  - Chronic granulocytic leukemia: reassessment of morphologic and cytogenetic
      characteristics in Ph1-positive and Ph1-negative cases.
AB  - 33 cases of chronic granulocytic leukemia (CGL) were reassessed to determine if,
      by strict morphologic criteria. Philadelphia chromosome (Ph1)-negative CGL exists
      as a diagnostic entity and if Ph1-positive CGL could be distinguished from Ph1
      negative CGL. Cases were reassessed using published criteria and, of 11 Ph1
      negative cases, only 4 could be reclassified as myelodysplastic syndromes or
      undifferentiated chronic myeloproliferative disorder. Of the morphologic
      parameters evaluated, peripheral blood basophilia and bicytopenia proved to be
      good discriminators between Ph1-positive and Ph1-negative cases. As a group, Ph1
      negative cases were more heterogeneous and tended to have lower hemoglobin, WBC,
      platelet count and absolute eosinophilia. Chromosomal abnormalities other than
      Ph1 were seen only in the Ph1-positive cases. Based on these findings, we
      conclude that Ph1-negative CGL constitutes a heterogeneous group, a subgroup of
      which is morphologically identical with the Ph1-positive CGL. The parameters that
      best discriminate between Ph1-positive and Ph1-negative cases are peripheral
      blood absolute basophilia and bicytopenia.

PMID- 1995327
TI  - Retinoic acid inhibits sodium butyrate-induced monocytic differentiation of HL60
      cells while synergistically inducing granulocytoid differentiation.
AB  - The human myeloid leukemia cell line HL60 is an in vitro model to study myeloid
      differentiation. HL60 cells differentiate along different cell type lineages in
      response to a variety of compounds. The direction of differentiation is usually
      inducer-specific. However, the response of HL60 cells to sodium n-butyrate (NaB)
      is pleiotropic. NaB induces HL60 along the monocytic, neutrophilic, eosinophilic,
      and basophilic pathways. In this study we saw that physiologic concentrations of
      all-trans-retinoic acid (RA) switched the direction of NaB-induced
      differentiation from monocytic to granulocytic. We showed previously (Breitman &
      He, Cancer Res 1990: 50: 6268-6273) that combinations of RA and NaB
      synergistically induce HL60 to cells that reduce nitroblue tetrazolium. The
      present study shows that this synergy was even greater if the parameter measured
      was mature granulocytes. Our results raise the possibility that the endogenous RA
      in the serum used to grow cells in culture may affect the direction of
      differentiation of HL60 cells induced by NaB. Furthermore, our results may
      provide additional rationale for the use of combinations of RA and NaB in the
      treatment of some leukemias.

PMID- 1995328
TI  - B-Z DNA reversible conformation changes effected by high pressure.
AB  - There are numerous data showing that a DNA molecule with alternate pirymidine
      purine sequence can adopt a left-handed, double-helical Z-DNA conformation. Such
      structural changes of DNA occur as a consequence of environmental conditions
      (e.g. 4 M NaCl) or chemical modification (e.g. methylation or bromination of
      bases). In this paper, we found for the first time that high pressure (several
      kilobars) can change the DNA conformation from the B to the Z form. When the
      pressure is reduced to an atmospheric one, DNA conformation returns back to the B
      form. The Z-DNA structure formation was confirmed by circular dichroism (CD) and
      ultraviolet (UV) measurements. However, we found, that the values of the ratio of
      absorbance at the wavelengths 295 and 257 nm in the range of 0.3-0.4 is not a
      fully conclusive proof for the Z-DNA conformation. Although the ratio is typical
      for Z-DNA form, it is not obvious that the negative band in CD spectrum will be
      observed. On the other hand, methylated DNA does not undergo B----Z DNA
      transitions at the high pressure. These conformational changes of DNA molecules
      could be interpreted as the effect a of different hydration of various DNA forms.

PMID- 1995329
TI  - A new family of small (5 kDa) protein inhibitors of insect alpha-amylases from
      seeds or sorghum (Sorghum bicolar (L) Moench) have sequence homologies with wheat
      gamma-purothionins.
AB  - Three isoinhibitors of locust and cockroach gut alpha-amylases were purified from
      seeds of sorghum by saline extraction, precipitation with ammonium sulphate,
      affinity chromatography on Red-Sepharose and preparative RP-HPLC on Vydac C18.
      The complete primary structures were determined by automatic degradation of the
      intact reduced and S-alkylated proteins, and by manual DABITC/PITC
      microsequencing of peptides obtained from enzyme digests. The inhibitors consist
      of 47 (SI alpha-1) or 48 (SI alpha-2, ST alpha-3) amino acids, and are the
      smallest plant inhibitors of alpha-amylase currently known. The sequences of the
      three isoinhibitors exhibit between 38% and 87% identity among themselves and
      also have homology (32-81%) with the gamma-purothionins recently isolated from
      wheat endosperm.

PMID- 1995330
TI  - A 28 kDa mitochondrial protein is radiolabelled by crosslinking with a 125I
      labelled presequence.
AB  - A 13-residue peptide containing the first 12 amino acids of the N-terminal part
      of the signal sequence of yeast cytochrome c oxidase subunit IV is shown by
      chemical crosslinking to interact with a mitochondrial protein. This result is
      obtained with mitochondria from four different origins. Submitochondrial
      localization experiments suggest that the 28 kDa labelled component is present on
      the outer face of the inner membrane. Since such addressing peptides are imported
      into mitochondria through the same machinery as protein precursors, the 28 kDa
      protein might be a component of the translocation apparatus.

PMID- 1995331
TI  - Closely related isozymes of alcohol dehydrogenase. Carboxymethylation: gamma 1
      gamma 1 differs widely from both beta 1 beta 1 and its equine equivalence EE.
AB  - Human gamma 1 gamma 1 alcohol dehydrogenase is quite insensitive to inactivation
      by iodoacetate, its equine counterpart EE highly sensitive, and the human beta 1
      beta 1 form intermediately sensitive. Imidazole hardly influences the iodoacetate
      inactivation of gamma 1 gamma 1, enhances that of EE and decreases that of beta 1
      beta 1. In all isozymes, metal-binding Cys residues are the most reactive, but
      the patterns for those binding the active site zinc atom differ. In phosphate,
      Cys-46 is most sensitive in EE and gamma 1 gamma 1, Cys-174 in beta 1 beta 1.
      This difference appears to correlate with the absence or presence, respectively,
      of an extra methyl group in the side-chain at position 48 (Ser in EE and gamma 1
      gamma 1, Thr in beta 1 beta 1). In imidazole, the reactivity in beta 1 beta 1 is
      shifted to Cys-46, while the specificity is enhanced in EE and decreased in gamma
      1 gamma 1. Thus, the inactivations illustrate large differences among structures
      closely related.

PMID- 1995333
TI  - The protein kinase inhibitor, K-252a, decreases elicitor-induced Ca2+ uptake and
      K+ release, and increases coumarin synthesis in parsley cells.
AB  - An elicitor preparation from fungal cell walls known to induce coumarin synthesis
      in suspension-cultured parsley cells also elicits a rapid and transient Ca2+
      uptake, K+ release and external alkalinization, and increases uptake of 45Ca2+
      into the cells. The latter three responses were inhibited by the protein kinase
      inhibitor K-252a at 0.2 microM. Elicitor-induced coumarin synthesis, a process
      which requires gene activation, was greatly enhanced by K-252a. These results
      suggest that protein phosphorylation might be involved in the initial steps of
      signal transduction as well as in the long-term induction of coumarin synthesis.

PMID- 1995332
TI  - Neoplastic epithelial cells express alpha-subunit of muscle nicotinic
      acetylcholine receptor in thymomas from patients with myasthenia gravis.
AB  - We studied the expression of mRNAs coding for the alpha-subunit of the muscle
      nicotinic acetylcholine receptor (AChR) in thymomas from patients with myasthenia
      gravis (MG). Northern blot analysis failed to detect the expression, but
      amplification of mRNAs derived from thymomas by reverse transcription and
      polymerase chain reaction produced the DNA fragments containing the nucleotide
      sequence coding for part of the alpha-subunit. We further revealed that the alpha
      subunit mRNA was derived from neoplastic epithelial cells of thymoma. Our results
      support the hypothesis that AChR expressed in thymoma is a candidate for the
      primary antigen which induces autoimmune responses to muscle AChR. The close
      relationship between MG and thymoma may be at least in part explained by this
      hypothesis.

PMID- 1995334
TI  - Quinone methide as a reactive intermediate formed during the biosynthesis of
      papiliochrome II, a yellow wing pigment of papilionid butterflies.
AB  - Mushroom tyrosinase and the recently identified, 4-alkyl-o-benzoquinone: 2
      hydroxy-p-quinone methide isomerase were used to investigate the mechanism of
      biosynthesis of papiliochrome II pigment found in the yellow scales of the
      papilionid butterflies. Incubation of N-beta-alanyldopamine (NBAD) and L
      kynurenine with mushroom tyrosinase resulted in the formation of adducts
      tentatively characterized as NBAD quinone-L-kynurenine adducts. If quinone
      isomerase was included in this reaction mixture, the formation of two new
      products could be witnessed. These two products exhibited the same retention time
      and the same UV and visible spectral properties as those of papiliochrome II
      diastereoisomers. Since quinone isomerase catalyzes the conversion of quinones to
      quinone methides, the above studies indicate that papiliochrome II biosynthesis
      involves non-enzymatic and hence non-stereoselective condensation of
      enzymatically generated NBAD quinone methide with L-kynurenine.

PMID- 1995335
TI  - cDNA cloning of a novel cdc2+/CDC28-related protein kinase from rice.
AB  - A cDNA clone, named R2, has been isolated by screening a rice cell cDNA library
      with a redundant oligonucleotide probe derived from the conserved ATP binding
      site of cdc2+/CDC28 protein kinases. The cDNA contained the entire coding
      sequence for a 424 amino acid polypeptide with a molecular mass of 47.6 kDa. The
      R2 mRNA, 2.1 kb in size, was expressed in both cultured rice cells and rice
      seedlings at similar levels. The predicted R2 protein has canonical motifs for
      ATP binding and catalysis, and is significantly homologous (up to 47%) to members
      of the cdc2+/CDC28 subfamily of serine/threonine protein kinase. The R2 protein
      is a novel member of the subfamily.

PMID- 1995336
TI  - Differential effect of extracellular calcium on the Na(+)-K+ pump activity in
      intact polymorphonuclear leucocytes and erythrocytes.
AB  - The effect of extracellular calcium on the Na(+)-K+ pump activity in human
      polymorphonuclear leucocytes and erythrocytes was studied and compared with the
      activity in mixed peritoneal leucocytes from rats. While there was maximal
      decrease in the pump activity (25-30%) of leucocytes from both rat and human by
      calcium 0.6 mM, a concentration of 0.1 mM caused a substantial decrease
      indicating a high sensitivity for extracellular calcium. In contrast, calcium had
      no effect on the pump activity in erythrocytes. The effect of calcium on the pump
      activity in leucocytes may be due to regulation of the influx of sodium across
      the plasma membrane, since in human leucocytes calcium had no effect on the pump
      activity if the cells were loaded with sodium.

PMID- 1995337
TI  - Induction of programmed cell death (apoptosis) in mature lymphocytes.
AB  - The apoptosis of human peripheral blood lymphocytes was analyzed by the breakdown
      of DNA into oligonucleosome-sized fragments. The mature lymphocytes were rendered
      sensitive to apoptosis by either the omission of fetal bovine serum in the
      culture medium or the addition of polymyxin B. In the first case it was
      counteracted by phorbol myristate acetate. The possible involvement of protein
      kinase C in cell survival is pointed out.

PMID- 1995338
TI  - Amino acid sequences of nerve growth factors derived from cobra venoms.
AB  - Amino acid sequences of nerve growth factors (NGFs), purified from the venoms of
      Indian cobra (Naja naja) and Thailand cobra (Naja naja siamensis) were
      determined. The sequence of N. naja NGF differed from that reported previously by
      Hogue-Angeletti et al. [(1976) Biochemistry 15, 26-34]. The sequence of N. naja
      siamensis NGF was identical to that of Formosan cobra Naja naja atra NGF,
      determined previously by Oda et al. [(1989) Biochem. Int. 19, 909-917] and to
      that deduced from the nucleotide sequence of an NGF cDNA from the venom gland of
      N. naja siamensis, as reported by Selby et al. [(1987) J. Neurosci. Res., 18, 293
      298].

PMID- 1995339
TI  - Isolation of a new gene (SW A2) encoding an alpha-amylase from Schwanniomyces
      occidentalis and its expression in Saccharomyces cerevisiae.
AB  - A new gene (SW A2) encoding a secretory alpha-amylase activity from
      Schwanniomyces occidentalis has been cloned from this yeast and then expressed in
      Saccharomyces cerevisiae. Both Sw, occidentalis and a transformant of S.
      cerevisiae incorporating SW A2 contain a transcript of 2.1 kb which hybridizes to
      DNa carrying the SW A2 gene. This indicates that the transcript is a product of
      the SW A2 gene. Transcription of the SW A2 gene seems to be regulated in both Sw.
      occidentalis and S. cerevisiae. Furthermore, the secretion of alpha-amylase
      activity is drastically repressed by glucose in both Sw. occidentalis and a
      transformant of S. cerevisiae containing SW A2.

PMID- 1995340
TI  - Physico-chemical properties of actin cleaved with bacterial protease from E. coli
      A2 strain.
AB  - The 36 kDa fragment of actin molecule obtained with the protease from E. coli A2
      strain [(1988) FEBS Lett. 228, 172] was shown to begin with Val-43 and retain the
      COOH-terminal amino acid residues of the parent molecule. The E. coli protease
      split actin preserves the NH2-terminal part of the polypeptide chain as well as
      the native conformation of actin molecule. However, the E. coli protease split
      actin failed to polymerize in 0.1 M KCl, suggesting that integrity of actin
      molecule between Gly-42 and Val-43 is crucial for actin polymerization.

PMID- 1995341
TI  - Evidence for gene duplication forming similar binding folds for NAD(P)H and FAD
      in pyridine nucleotide-dependent flavoenzymes.
AB  - For pyridine nucleotide-dependent flavoenzymes, binding both FAD and NAD(P)H on a
      single amino-acid chain, we have found a high degree of internal sequence
      similarity for certain regions of the FAD and NAD(P)H binding portions of the
      chain for any given protein. This was the case for a range of enzyme classes,
      including disulphide oxidoreductases (such as glutathione reductase,
      trypanothione reductase, lipoamide dehydrogenase, mercuric reductase), mono- and
      dioxygenases, nitrite reductase, alkyl hydroperoxidase and NADH dehydrogenase
      from E. coli. This provides strong support for gene duplication as the origin of
      at least part of the FAD and NAD(P)H recognising domains of such enzymes.

PMID- 1995342
TI  - An upward shift of intracellular pH rather than the final absolute pH value is
      critical for controlling gap junction permeability in tumor promoter-treated
      cells.
AB  - The tumor promoter TPA is found to inhibit gap junction permeability in monolayer
      cultures of hamster fibroblasts. This effect is associated with an increase in
      intracellular pH. Here we show that neither an increase in pHi alone nor TPA
      treatment under conditions preventing pHi-shift affect gap junction permeability.
      It is not the level of pHi reached, but rather the pHi-shift itself that is
      essential for the inhibition of gap junction permeability in the presence of TPA.

PMID- 1995343
TI  - The decreased level of casein kinase 2 in brain cortex of schizophrenic and
      Alzheimer's disease patients.
AB  - The content of casein kinase 2 is considerably decreased in ribosome-free
      extracts of the frontal cortex of schizophrenic and Alzheimer's disease patients
      in comparison to normal brains as has been demonstrated by means of
      immunoblotting. The activity of casein kinase 2 towards endogenous substrates and
      casein is also diminished in the cases of mental pathologies examined. This
      phenomenon may explain the well-known aberrations in the phosphorylation of
      structural proteins of human brain which are intrinsic for the mental diseases.

PMID- 1995344
TI  - Inositol 1,4,5-triphosphate phosphatase activity in membranes isolated from
      amphibian skeletal muscle [corrected].
AB  - The hydrolysis of [3H]inositol 1,4,5-trisphosphate by a soluble fraction and by
      isolated transverse tubule and sarcoplasmic reticulum membranes from frog
      skeletal muscle was studied. Transverse tubule membranes displayed rates of
      hydrolysis several-fold higher than those of sacroplasmic reticulum and soluble
      fraction; Km and Vmax were 25.2 microM and 44.1 nmol/mg/min, respectively.
      Transverse tubule membranes sequentially hydrolyzed inositol trisphosphate to
      inositol bisphosphate, inositol 1-phosphate and inositol, indicating that these
      membranes have inositol bis- and monophosphatases in addition to inositol
      trisphosphatase.

PMID- 1995346
TI  - A structure-derived sequence pattern for the detection of type I copper binding
      domains in distantly related proteins.
AB  - A structure-based approach to the definition of sequence patterns characteristic
      of protein domains is presented by example. The approach requires a multiple
      sequence alignment of a family (or set of related families) as well as at least
      one three-dimensional structure. The pattern derived does not merely summarize
      the information in the known sequences but attempts to generalize the pattern
      specifications based on structural insight. In this example, the pattern-driven
      database search identified correctly most of the known type I copper-binding
      domains and detected the presence of a homologous domain in a previously unknown
      case (CopA protein). The significance of these results is discussed.

PMID- 1995345
TI  - Absence of calponin phosphorylation in contracting or resting arterial smooth
      muscle.
AB  - We have tested the hypothesis of Winder and Walsh [(1990) J. Biol. Chem. 265,
      10148] that the contractile state of smooth muscle is regulated by calponin
      phosphorylation. Porcine carotid arterial muscles were highly labeled with 32P,
      then contracted with four different agents for various times. No radioactivity
      was detected in calponin isolated by 2D or 1D gel electrophoresis from the
      muscles. Similarly, resting muscles showed no [32P]phosphate in calponin.
      Apparently the sites of calponin available for phosphorylation in vitro are
      rendered unavailable in the intact muscle.

PMID- 1995347
TI  - Does aminotriazole inhibit import of catalase into peroxisomes by retarding
      unfolding?
AB  - Fusion of complementary cell lines from patients with diseases of peroxisome
      biogenesis leads to peroxisome assembly in the heterokaryons and to uptake of
      cytosolic catalase by the newly assembled peroxisomes. Here we show that catalase
      import is inhibited by prior binding to catalase of the inhibitor 3-amino-1,2,4
      triazole, which appears to retard unfolding of the protein.

PMID- 1995348
TI  - A chimeric D2 dopamine/m1 muscarinic receptor with D2 binding specificity
      mobilizes intracellular calcium in response to dopamine.
AB  - Using PCR methodology, a chimeric receptor cDNA was constructed in which the
      entire third cytoplasmic loop of the human D2 dopamine receptor was replaced by
      the analogous portion of the human m1 muscarinic receptor. When expressed in CHO
      cells, the chimeric D2/m1 receptor bound dopaminergic ligands with affinities
      similar to the native D2(414) receptor. Intracellular calcium levels (measured
      with Fura-2) were not altered when CHO cells expressing the D2(414) receptor were
      exposed to dopamine. In contrast, dopamine elevated intracellular calcium levels
      in cells expressing the D2/m1 chimeric receptor in a dose-dependent manner which
      was blocked by the D2 antagonist, fluphenazine. The ability to construct G
      protein-linked receptor chimeras which mobilize calcium with nearly unaltered
      pharmacologic specificity raises the possibility of a generic strategy for
      creating non-radioisotopic reporter systems for use in drug discovery.

PMID- 1995350
TI  - Proteolytic inactivation of human alpha 1 antitrypsin by human stromelysin.
AB  - alpha 1 Antitrypsin (alpha 1AT) is the main physiological inhibitor of neutrophil
      elastase, a serine protease which has been implicated in tissue degradation at
      inflammatory sites. We report here that the connective tissue metalloproteinase,
      stromelysin, cleaved alpha 1AT (54 kDa), producing fragments of approximately 50
      kDa and 4 kDa, as shown by gel electrophoresis. The cleavage of alpha 1AT was
      accompanied by inactivation of its elastase inhibitory capacity. Isolation of the
      4 kDa fragment by reversed-phase HPLC, followed by N-terminal amino acid
      sequencing, demonstrated that the cleavage of alpha 1AT occurred at the Pro357
      Met358 (P2-P1) peptide bond, one peptide bond to the N-terminal side of the
      inhibitory site. We suggest that stromelysin may potentiate the activity of
      neutrophil elastase by proteolytically inactivating alpha 1AT.

PMID- 1995349
TI  - Highly conserved sequences in the 3'-untranslated region of the COL1A1 gene bind
      cell-specific nuclear proteins.
AB  - Sequencing of the 3' untranslated region (3'-UTR) of the human COL1A1 gene
      revealed numerous putative regulatory motifs and two highly conserved regions
      flanking the two polyadenylation sites. The conserved regions were separated by
      about 700 bp of less conserved sequences. The first region consists of almost all
      the 3'-UTR of the shorter (4.8 kbp) COL1A1 transcript. The second conserved
      domain includes a motif shared with several collagen genes. Both conserved
      domains bind cell-specific nuclear proteins suggesting that the 3'-UTR is
      important for cell specific expression of the COL1A1 gene.

PMID- 1995351
TI  - ATP-sensitive K channels in heart muscle. Spare channels.
AB  - We show that ATP-sensitive K+ channels of excised inside-out membrane patches of
      rat ventricular myocytes show considerable variation in their sensitivity to ATP.
      In 102 different membrane patches IC50 values ranged from 9 to 580 microM ATP and
      Hill coefficients from 1% to 6.41% of patches showed openings of ATP-sensitive K+
      channels in the presence of 1 mM ATP. These results considerably widen the range
      of internal ATP concentrations over which one might expect activation of the ATP
      sensitive K+ current in cardiac myocytes.

PMID- 1995352
TI  - Breast cancer and pregnancy.

PMID- 1995353
TI  - The use of CA15.3 as a serum tumour marker in breast carcinoma.
AB  - There is, as yet, no tumour marker which is sufficiently specific and sensitive
      for use in the routine assessment of breast cancer patients. CA15.3 is a recently
      described tumour marker determined by two monoclonal antibodies. We have
      estimated CA15.3 by immunoradiometric assay in 187 patients attending a breast
      clinic. Eighty-one patients with benign disease were used as controls and 32 U/ml
      was taken as the upper limit of the normal range (means + 3SD = 31.7). Of 58
      women with Stage I and II disease, only four had abnormal concentrations of
      CA15.3 and all are disease-free at a mean follow-up of 31 months. Seven women
      with normal CA15.3 concentrations developed recurrent disease at a mean of 18.7
      months (range 10-25 months). Seven-day postoperative values were significantly
      lower than pre-operative values. There was no association between the CA15.3
      value and the axillary nodal status. The patients with disseminated disease had a
      wide range of CA15.3 concentrations and there was no association between the
      CA15.3 concentration and the apparent tumour load.

PMID- 1995354
TI  - A 10-year experience of tamoxifen as primary treatment of breast cancer in 100
      elderly and frail patients.
AB  - Between 1977 and 1983 100 elderly women (median 76.3 years) with breast cancer
      were treated with tamoxifen as primary therapy. The median follow-up is 59
      months. Sixty-eight responded (40 CR and 28 PR) with median response durations of
      47 months and 26 months respectively. Twenty-two patients had disease
      stabilization for a median of 15.5 months and 10 had progressive disease. The
      median time to best response was 13.5 weeks for patients achieving CR and 14
      weeks for those with PR. Oestrogen receptor values were obtained in 37 patients
      of which two patients had no ER detectable. Sixty-seven per cent of ER-unknown
      patients responded compared with 74% of ER-rich. Likelihood of response did not
      appear to depend upon T-stage or age. Survival was better than that of an
      unmatched historical group treated with surgery/radiotherapy and compares
      favourably with recent reports. Although 35% have died of breast cancer, 25% died
      of other causes and 22% remained free of recurrence at the time of reporting or
      at death. Only 11% underwent subsequent mastectomy/lumpectomy and the most
      frequent subsequent treatments were radiotherapy to the breast (32%) and further
      hormonal therapies (40%). Tamoxifen is a practical primary therapy of breast
      cancer in elderly and frail women obviating the need for surgery in a high
      proportion of cases.

PMID- 1995355
TI  - Quantifying the risk of breast cancer.
AB  - Although all women are potentially breast cancer sufferers, we need to develop a
      risk index in order to recognize the most vulnerable. Multiple promoting factors
      are suspected in breast cancer and recent research suggests that different types
      of clinical risk factor may interact to multiply a women's risk. Such women
      require skillful counselling with more frequent monitoring and advice about
      possible protective measures.

PMID- 1995356
TI  - Limited resection for Stage I lung cancer.
AB  - We have reviewed our experience of limited resections for Stage I lung cancer for
      the years 1971-88. Sixty-one cases of sublobar resection (wedge or segmental)
      were compared with 411 lobar resections (lobectomies or bilobectomies), performed
      over the same period. Operative mortality was 0% in the limited resection group
      and 3% (12/411) in the control group. Cancer recurrence was detected respectively
      in 36% and 38% of patients, and actuarial survival at 5 years was 55% versus 49%
      overall. Sublobar resection had a slightly better outcome than lobar resection in
      pathological T1 (5-year survival of 73% vs 55%) but a worse outcome in pT2 (35%
      vs 46%); however, none of the differences was statistically significant. In 28
      patients with pre-existing cardiac or pulmonary co-morbidity, limited resection
      yielded the same 5-year survival as lobectomy (53% vs 51%) with no peri-operative
      deaths (0 vs 5%). Although derived from a retrospective analysis, these data
      offer a further confirmation that limited resection combined with adequate nodal
      staging is a reliable and effective technique for early stage lung cancer
      management.

PMID- 1995357
TI  - Lung adenocarcinoma is more sensitive than gastric adenocarcinoma to anticancer
      drugs in vitro.
AB  - The chemosensitivities of 26 lung adenocarcinoma tissues were compared to those
      of 110 gastric adenocarcinoma tissues, using the in vitro succinate dehydrogenase
      inhibition (SDI) test. Tumour tissues obtained at surgery were exposed to five
      different anticancer drugs: carboquone (CQ), adriamycin (ADM), mitomycin C (MMC),
      cisplatin (DDP) and 5-fluorouracil (5-FU). The lung adenocarcinomas showed a
      statistically significant reduction in succinate dehydrogenase (SD) activity,
      compared to the gastric adenocarcinomas, after exposure to each drug. The
      chemosensitivity was defined as a reduction in SD activity to 50% of control or
      less. Lesser degrees of reduction in SD activity were defined as drug resistance.
      The sensitivity rates to ADM, MMC and DDP, respectively, were significantly
      higher in the lung than in the gastric adenocarcinomas. Tumour cells from 22
      (84.6%) of the 26 lung adenocarcinoma tissues showed a sensitivity to more than
      three drugs, whereas the rate was only 46.4% (51/110) for the gastric
      adenocarcinomas. The rate of resistance to all the drugs tested was 3.8% (1/26)
      for the lung adenocarcinomas, in contrast to the 20.9% (23/110) seen with the
      gastric adenocarcinomas. Thus, while adenocarcinomas of the lung and stomach both
      show clinical resistance to anticancer agents, the chemosensitivity of the lung
      tissues is greater. In the light of these observations, attention must be
      directed to improving specific drug delivery systems.

PMID- 1995358
TI  - Clinical evaluation of combined use of CEA, CA19-9 and CA50 in the serum of
      patients with pancreatic carcinoma.
AB  - CEA, CA19-9 and CA50 are tumour-associated antigens defined by monoclonal
      antibodies that have been raised against adenocarcinoma cell lines, but no single
      antibody is specific for the detection of pancreatic malignancy. The aim of this
      study was to determine whether the combined use of CEA, CA19-9 and CA50 would
      improve diagnostic accuracy. An immunoradiometric assay was used for the
      detection of CEA and CA19-9 and the Delfia system for CA50. Serum was collected
      from 65 normal subjects, 16 with pancreatitis and 28 with pancreatic carcinoma.
      Of the 28 cancer patients, 24 (85%) had a CA19-9 level above 46 mu/ml, 26 (92%)
      had a CA50 level above 21 mu/ml and 10 (37%) had a CEA level above 7 ng/ml.
      Multivariant discriminant analysis on the combined antibodies showed that 96% of
      the malignant group, 13% of the pancreatitis group and 11% of the normal group
      were positive, with an overall correct classification of 91% into the three
      groups (multivariant discriminant analysis P less than 0.05). Thus the combined
      use of CEA, CA19-9 and CA50 improves diagnostic accuracy in differentiating
      benign from malignant disease of the pancreas.

PMID- 1995360
TI  - CEA and NCA levels in peripheral and tumour venous blood of patients with gastric
      and colonic carcinomas estimated by RIA and EIA methods.
AB  - Carcinoembryonic antigen (CEA) and nonspecific cross-reacting antigen (NCA)
      levels in draining tumour blood were compared with concentrations of these
      antigens in peripheral blood of patients with gastric and colonic malignancies.
      The controls were cases with gastric and duodenal ulcers. The results obtained by
      radioimmunoassay (RIA) were compared with enzyme immunoassay (EIA). It was shown
      that patients with high CEA levels in draining tumour blood also had elevated
      values of this antigen in peripheral blood, but that the CEA values in blood
      flowing from tumours were usually higher than in peripheral blood. CEA
      concentrations in tumour venous blood and in peripheral blood depended on
      clinical advancement and neoplastic venous invasion. NCA determination had no
      significance in clinical monitoring of studied neoplasms. CEA level
      determinations performed by the RIA using CEA standard prepared in our laboratory
      and assays with use of Abbott CEA-EIA kit gave fully comparable results.

PMID- 1995359
TI  - Effect of repeated intraperitoneal chemotherapy with epirubicin on the hepatic
      transport of bile acids and their enterohepatic circulation.
AB  - The effect of repeated intraperitoneal perfusion with epirubicin on the clearance
      of 14C-taurocholate by the liver and the enterohepatic circulation of the
      synthetic bile acid 75-SeHCAT were investigated using a rat model. After six
      treatments there was no significant difference in the transport rate constants
      (plasma to liver, liver to bile and liver to plasma) between and within the
      saline and epirubicin groups. Similarly, there were no differences detected
      between the groups for the parameters derived from these transport rate
      constants. Thus the initial plasma clearance after six perfusions was 39 +/- 9,
      and 36 +/- 11 ml/min/kg in the epirubicin and saline groups respectively. The
      excretory efficiency of the liver at this stage was identical: 67 +/- 10% in the
      epirubicin treated animals and 67 +/- 6% in the saline controls. A deterioration
      in the SeHCAT retention was observed after repeated intraperitoneal perfusion in
      both groups. This was significant only in the cytotoxic group, between the first
      and sixth epirubicin perfusion: 59 +/- 9% vs 48 +/- 9% at 24 h (P = 0.03), 31 +/-
      8% vs 22 +/- 5% at 48 h (P = 0.019) and was not cumulative beyond this stage.
      These findings indicate that repeated intraperitoneal perfusion chemotherapy with
      epirubicin does not impair bile acid clearance by the hepatocyte. The decrease in
      the retention of SeHCAT is unlikely to be the result of epirubicin-induced ileal
      mucosal damage since the reduction was not cumulative beyond 48 h of
      administration of the compound.

PMID- 1995361
TI  - Advanced rectal cancer in the female: reduction of pelvic recurrence by rectal
      resection en bloc with hysterectomy and/or posterior vaginal wall excision.
AB  - The authors report their experience with 20 female patients with advanced rectal
      cancer in whom rectal excision was combined with concomitant excision of the
      uterus and/or posterior vaginal wall. Six patients presented with a malignant
      fistula between the rectum and the genital tract; 10 had pre-operative
      radiotherapy, with a total dose of 50 Gy in seven patients and 30 Gy in three.
      The resection was judged as radical in 18 patients; the specimen was staged as a
      Dukes' B in eight and a Dukes' C in 10 cases. Three patients died within the
      follow-up period, due to intercurrent disease, without evidence of recurrence.
      Seven patients have been followed without evidence of disease for an average of
      91 months (range 39-143 months). One patient is alive 5 years after surgery with
      a pelvic recurrence. Seven patients succumbed to distant metastases alone (n = 4)
      or to a combination of haematogenous metastases and pelvic recurrence (n = 3).
      The authors make a plea for local radicality in advanced rectal cancer in female
      patients, to preserve quality of life in most patients and a cure in some.

PMID- 1995362
TI  - Limb salvage in soft tissue sarcomas with selective combination of modalities.
AB  - One hundred and seventy-one consecutive patients with soft tissue sarcomas were
      treated in the period 1977-1986. Of 144 patients with extremity sarcomas, only
      eight (6%) were managed with amputation. The overall estimated 5-year survival
      rate is 64%, and that for patients with extremity tumors is 71%. The 5-year local
      recurrence rate in extremity sarcomas was 6% for patients with minimum surgical
      margins 2 cm or greater and no further local therapy, and 6% for those with
      narrower surgical margins and adjuvant postoperative radiation; 80 patients (56%)
      were in the former group and 64 (44%) in the latter. With a selective combination
      of modalities, limb salvage can now be practiced in 94% of the patients with
      acceptable local control and survival rates.

PMID- 1995363
TI  - Seven different primary cancers in a single patient. A case report and review of
      multiple primary malignant neoplasia.
AB  - A 43-year-old female developed seven different primary carcinomas over a 14-year
      period. Six were adenocarcinomas and one a squamous carcinoma. Five of the six
      adenocarcinomas were locally advanced, but only two recurred after excision.
      There are very few reports in the literature of patients with seven or more
      primary cancers, but all demonstrated a remarkable absence of metastatic disease
      and surprisingly prolonged survival. They represent extreme examples of the
      phenomenon of multiple primary malignant neoplasia (MPMN) and the possibility of
      their belonging to a cancer family syndrome should always be considered.

PMID- 1995364
TI  - Breast metastasis from nasopharyngeal carcinoma.
AB  - The first two cases of breast metastases from anaplastic carcinoma of the
      nasopharynx are presented. In both cases the breast metastasis was solitary, but
      there was no delay in confirming their metastatic nature since both lesions
      manifested after the documentation of disseminated disease. The difference in
      histology, since 99% of our nasopharyngeal carcinoma patients have anaplastic
      carcinoma of poorly differentiated carcinoma subtype, makes it easy to
      differentiate them from primary breast cancer by cytology or histology.

PMID- 1995366
TI  - Collaborative practice.

PMID- 1995367
TI  - Lipid education.

PMID- 1995368
TI  - Implementing a ventricular assist device program. A partnership between nursing
      and clinical engineering.
AB  - VAD programs continue to expand as research evolves and this treatment modality
      becomes more available. Implementation of these programs requires a strong
      commitment to team development, collaboration, and ongoing education. We believe
      that the partnership between nursing and clinical engineering captures these key
      aspects. This alliance facilitates learning and professional growth and supports
      overall program goals. Beyond VAD programs, medical and technologic advances will
      continue to have an impact on the critical care environment, increasing the
      complexity of patient care. Our successful partnership has set the stage for
      essential collaboration between nursing and clinical engineering in the future.

PMID- 1995369
TI  - Why have a living will?

PMID- 1995370
TI  - Volumetric interstitial hyperthermia: role of the critical care nurse.
AB  - Although statistical survival of patients with malignant brain tumor is dismal
      and their care can be emotionally exhausting, it is hopeful and rewarding to the
      critical care nurse to participate in a clinical investigation that will improve
      the future of these patients. Each therapy cycle administered, each patient
      treated, and each family member is different; each is a challenge for the
      critical care nurse. The quality and success of a clinical investigation requires
      the commitment of many people working together in close team effort. With
      effective communication, insight, and cooperation the critical care nurse working
      in this research setting shares in the patient's and family's hope and
      determination for the future of improved medical and nursing management of
      malignant brain tumors.

PMID- 1995372
TI  - Fact of myth? Patients with pulmonary disease should be placed in the semi
      Fowler's position.

PMID- 1995371
TI  - Introducing standardized care plans in an intermediate care setting.

PMID- 1995373
TI  - Temporary atrial pacing after cardiac surgery.
AB  - Atrial epicardial wires are used after cardiac surgery for diagnostic and
      therapeutic purposes. Postoperative dysrhythmias may be diagnosed by using an
      atrial wire electrogram, and treatment of these dysrhythmias includes atrial
      pacing. In this article atrial pacing during the post-cardiac surgery period is
      discussed in relation to the management of supraventricular dysrhythmias,
      bradydysrhythmias, ventricular dysrhythmias, and low cardiac output.

PMID- 1995374
TI  - Maintaining an effective preceptor program.

PMID- 1995376
TI  - Being all I can be!

PMID- 1995375
TI  - A little good news.

PMID- 1995377
TI  - Vaginal infections, cervical ripening and preterm delivery.
AB  - A prospective study is presented which addresses the relative effect of
      cervicovaginal infection and precocious maturation of the uterine cervix on
      preterm delivery. From April 1981 through December 1983, a total of 5758 pregnant
      women were checked by means of a vaginal examination at every prenatal visit and
      a research for bacterial cervicovaginal infection whenever abnormal signs were
      observed. The study reveals that vaginal infection has no measurable effect when
      observed during the second trimester of pregnancy, and a small effect during the
      third trimester. This means that infection of the vagina or/and the cervix may be
      demonstrated as a risk factor only when the cervix is short before 28 weeks or
      open before 37 weeks.

PMID- 1995378
TI  - When is it possible to meet the wish of a woman to terminate her labour by
      caesarean section?
AB  - The authors have evaluated 311 answers of Czech obstetricians to the
      questionnaire concerning their attitude towards pregnant women that want to
      terminate their labour by caesarean section. The questionnaire contained six
      model situations: (1) normal delivery; (2) previous caesarean section; (3) breech
      presentation; (4) previous delivery of an injured baby; (5) protracted labour and
      (6) caesarean section apparently indicated by another obstetrician. In each
      situation the obstetrician was encouraged to choose from five different answers.
      The results have revealed the lack of unanimity in some cases, 3, 4 and 5. Here
      we feel that the obstetrician should meet the wish of the woman. However, in
      those situations that are clear from the medical point of view and where there is
      no professional indication for a caesarean section, it is in accordance with the
      Czechoslovak rule of law not possible to meet the wish of the woman.

PMID- 1995379
TI  - Changing trends in preterm childbirth.
AB  - Progress in perinatal care has been accompanied recently by increasing numbers of
      induced premature deliveries because of fetal distress. This is confirmed by
      study of 26,796 consecutive births in the Caen Hospital Group between 1980 and
      1987. Study of the fate of these children shows that this attitude has not led to
      any excess mortality when the share of the IPD before 32 weeks are regularly
      growing. This would imply that the prematurity rate is no longer a sufficiently
      accurate epidemiological index for the evaluation of prenatal care policies.

PMID- 1995380
TI  - Discrepancy between laboratory determination and visual estimation of blood loss
      during normal delivery.
AB  - Blood loss during normal delivery was measured in 37 primiparas and 25 multiparas
      who had no obstetric or medical complications and who underwent normal delivery
      in a teaching hospital following spontaneous onset of labour at term. Measured
      blood loss was significantly greater than the estimated volume of blood loss. In
      primigravidas, the mean ( +/- SE, standard error of the mean) estimated blood
      loss was 260 +/- 12 ml and the mean measured blood loss was 401 +/- 29 ml. In
      multiparas the mean estimated blood loss was 220 +/- 10 ml and the mean measured
      blood loss was 319 +/- 41 ml. The mean estimated blood loss was significantly
      lower (P less than 0.05) than the mean measured blood loss in both groups. The
      size of the discrepancy between measured and estimated blood loss was
      proportional to the measured blood loss. These findings show that visual
      estimation of blood loss was grossly inaccurate.

PMID- 1995381
TI  - The first attempt at IVF treatment. Results and requirements for a satisfactory
      success rate.
AB  - The purpose of this study was to report the success rate of the first IVF
      treatment in 161 patients who attended our department in 1988. The indications
      for IVF were tubal damage in 84 couples (52.1%), unexplained infertility and
      endometriosis (with patent tubes) in 61 couples (37.9%), and polycystic ovarian
      syndrome in 16 couples (10%). Clinical pregnancies were diagnosed in 40 patients,
      giving an overall clinical pregnancy rate of 35.4% per embryo transfer. In the
      group of patients with unexplained infertility or endometriosis one in three of
      the embryo transfer cycles will predictably result in a birth, one in four in the
      group of patients with tubal damage or polycystic ovarian syndrome. These results
      invite discussion of the possible reasons for the success of our IVF program.

PMID- 1995382
TI  - The use of an electric freezer in human semen banking.
AB  - The use of an electric freezer for cryostorage of human semen is described. A
      simple method for semen freezing in liquid nitrogen after dilution with 7.5%
      glycerol was used. Thawing for quality analysis revealed only a small decrease
      (10%) in post-thaw sperm motility (59 +/- 1.4 vs. 53 +/- 1.8%; mean +/- SE, n =
      12, P less than 10(-5)) and 14% in post-thaw sperm vitality (85.0 +/- 1.3 vs.
      72.9 +/- 1.8%). After the freezing process, the samples, three of each donor,
      were cryopreserved in a regular electric freezer which maintained temperatures in
      the range of -85 degrees C (+/- 2 degrees C). The samples were stored for 1 week,
      2 and 6 months, thawed and then assayed for motility and vitality. No effect of
      storage was found for a period up to 2 months. An additional decrease of 17.2% in
      sperm motility and 18% in sperm vitality were noted only after 6 months of
      preservation. The final motility and vitality rates of these sperm samples were
      44 +/- 2.4 and 60 +/- 3.0%, respectively. According to these results, in cases of
      sperm storage for limited periods, it is recommended to cryopreserve human semen
      by the use of a combination of freezing in liquid nitrogen and storage of the
      samples in an electric freezer at -85 degrees C.

PMID- 1995383
TI  - Human fetal mouthing movements: a potential biophysical variable for
      distinguishing state 1F from abnormal fetal behavior; report of 4 cases.
AB  - In late pregnancy, when fetal behavioural states are well developed, human
      fetuses spend about one third of their time in a quiescent state, 1F. In healthy
      fetuses biophysical tests often appear suboptimal if recording happens to occur
      in this state, and as a result prolonged recording may be necessary. We have
      examined fetal mouthing movements during state 1F in 65 fetuses beyond 36 weeks,
      with and without risk factors, but in whom there was no immediate evidence of
      compromise. We found that periodic rhythmical mouthing movements were a
      characteristic feature of state 1F, occurring in 93.0% of episodes, when the
      fetal mouth was visible. This compares favourably with variables of the
      biophysical profile, which were less likely to be satisfactory in state 1F -
      fetal breathing 53.8%, fetal movements 46.2%, fetal heart rate 69.2%, and overall
      biophysical score of 8 or 10, 60.0%. We identified objective evidence of fetal
      compromise (of various aetiologies) in four other fetuses of the same gestational
      age, and mouthing movements were absent in all four.

PMID- 1995385
TI  - Thanatophoric dwarfism; drugs and antenatal diagnosis; a case report.
AB  - Thanatophoric dwarfism is not as rare as once thought. We present this case
      because of the possible association with drug administration and the probability
      of diagnosing this condition antenatally.

PMID- 1995384
TI  - Group B streptococcal chorioamnionitis and neonatal septicemia following 8 days
      pivampicillin and metronidazol prophylaxis after premature rupture of membranes;
      a case report.
AB  - A case of preterm premature rupture of the membranes (PPROM) in the 31st week of
      gestation is reported. Initial cultures from the cervix and urine were without
      pathogenic microorganisms. After 8 days of prophylactic pivampicillin and
      metronidazol, culture from the cervix showed profuse growth of Group B
      Streptococci (GBS) and the patient developed symptoms of chorioamnionitis.
      Cesarean section was performed and the infant presented GBS-septicemia. In spite
      of continued treatment with pivampicillin, culture from the cervix on day 6 post
      partum still showed profuse growth of GBS. Prolonged prophylactic per oral
      administration of broad-spectrum antibiotics after PPROM may not always protect
      against infectious complications. Literature is reviewed, and it is discussed
      whether the applied regimen in some cases even may favour the occurrence of
      serious infections.

PMID- 1995386
TI  - The use of Doppler umbilical artery waveforms in placental abruption; a report of
      two cases.
AB  - In a prospective study, the predictive value of Doppler umbilical arterial
      velocimetry waveforms in detecting the fetus at risk was examined in ten patients
      with abruptio placenta. One patient suffered intra-uterine fetal death within 8 h
      of obtaining a normal reactive cardiotocograph and normal umibilical artery
      waveforms. In another patient with severe placental abruption, following 2500 ml
      of blood loss, the umbilical artery waveforms were normal. In this study,
      umbilical artery waveforms failed to predict fetal outcome in cases of placental
      abruption.

PMID- 1995387
TI  - Teleology of the menopause.

PMID- 1995388
TI  - An evaluation of clinical estimation of fetal weight and symphysis fundal
      distance for detection of SGA infants.
AB  - In 58 small for gestational age (SGA) infants and 141 non-SGA infants, the
      measuring of symphysis fundal distance (SF) was compared with clinical estimation
      of fetal weight in order to evaluate the efficacy of the two methods of
      predicting SGA. By regression analyses, the SF curve deviation explains 22% of
      the variation of birthweight. The estimated fetal weight (EFW) curve deviation
      explains 40%. By combining the two values, 42% of the variation in birthweight is
      explained. When receiver operating characteristic (ROC) curve analyses, Kappa
      index and relative risk were applied the clinical estimation of fetal weight by
      abdominal palpation was found to be as reliable a predictor of SGA at birth as
      the measurement of the SF distance. Statistical analyses of the SF curve and EFW
      curve do not improve the results compared with the last measurement of SF
      distance and EFW. Combination of the EFW and SF measurements results in a higher
      sensitivity (one test positive) or a higher predictive value (both tests
      positive). Only marginal additional diagnostic information was achieved, however,
      as the ROC curves, Kappa index and Relative risk were nearly unchanged,
      regardless of combination of EFW and SF measurements.

PMID- 1995389
TI  - The relationship between Apgar score, umbilical artery pH and operative delivery
      for fetal distress in 2778 infants born at term.
AB  - A total of 2778 infants born at term were studied to determine the relationship
      between Apgar scores after 1 min, umbilical artery pH values, mode of delivery, a
      diagnosis of fetal distress leading to operative delivery, and sex. Eighty-three
      percent of the population had normal Apgar scores (greater than or equal to 8)
      and normal pH values (greater than 7.15) in which 10% were operatively delivered
      for fetal distress (ODFD). Sixty-one percent of the children with low Apgar
      scores (less than or equal to 7) had normal pH values, and 74% of the infants
      with acidosis (pH less than or equal to 7.15) had normal Apgar score. Twenty-four
      percent of the infants with a low Apgar score and/or acidosis were ODFD
      (sensitivity). Ninety percent of the infants who had Apgar scores and pH values
      were not ODFD (specificity). The predictive value (a low Apgar score and/or
      acidosis) of ODFD was 33%, and the negative predictive value (normal Apgar score
      and a normal pH) of ODFD was 85%. A significantly higher incidence of ODFD and
      acidosis was found in boys.

PMID- 1995390
TI  - Emergence of the mature myosin phenotype in the rat diaphragm muscle.
AB  - Immunohistochemical analysis of myosin heavy chain (MHC) isoform expression in
      perinatal and adult rat diaphragm muscles was performed with antibodies which
      permitted the identification of all known MHC isoforms found in typical rat
      muscles. Isoform switching, leading to the emergence of the adult phenotype, was
      more complex than had been previously described. As many as four isoforms could
      be coexpressed in a single myofiber. Elimination of developmental isoforms did
      not usually result in the myofiber immediately achieving its adult phenotype.
      Activation of genes for specific adult isoforms might be delayed to puberty. For
      example, two of the three fast MHCs, MHC2X and MHC2A appeared perinatally, while
      MHC2B did not appear until 30 days postnatal. By Day 60 this isoform was present
      in approximately 27% of the myofibers, but in most myofibers expression of this
      isoform was transient (i.e., at Day greater than or equal to 115, less than 4% of
      the myofibers expressed MHC2B). Fibers which contained MHC beta/slow during the
      late fetal and early neonatal period coexpressed MHCemb. A marked increase in the
      frequency of fibers containing MHC beta/slow occurred between 4 and 21 days
      postnatal. These slow fibers arose from a population of myofibers which expressed
      MHCemb and MHCneo during their development, and they accounted for the majority
      of slow fibers found in the adult diaphragm. The adult myosin phenotype of the
      diaphragm myofibers (as determined with immunocytochemistry, and 5% SDS-PAGE) was
      not achieved until the rat was greater than or equal to 115 days old.

PMID- 1995391
TI  - Differentiation of delayed rectifier potassium current in embryonic amphibian
      myocytes.
AB  - The developmentally regulated expression of prolonged outward potassium currents
      influences the extent to which sustained inward currents contribute to the action
      potential at early stages of differentiation. In amphibian spinal neurons, the
      long duration and calcium dependence of the embryonic action potential and the
      amount of calcium influx are largely determined by the extent of maturation of
      the delayed rectifier potassium current (IKv). We have undertaken a parallel
      study of differentiation of myocytes, in which action potentials are brief and
      sodium-dependent even at early stages. The early expression of electrical
      excitability in embryonic amphibian myocytes growing in culture has been examined
      previously using intracellular voltage recording techniques. The membrane
      exhibits a delayed rectification in response to depolarization at times earlier
      than those at which impulses can first be generated. We have examined the
      differentiation of this outward current in embryonic myocytes developing in
      vitro, using whole cell voltage clamp. IKv is initially absent. When first
      recorded it is small and slowly activating but undergoes sixfold increases in
      both density and rate of activation during the first day in culture. This
      maturation is dependent upon transcription, and both rate and density are
      influenced by the presence of other cell types. The large amplitude of the
      outward delayed rectifier prevents expression of long duration action potentials.

PMID- 1995392
TI  - RNA-protein interactions of stored 5S RNA with TFIIIA and ribosomal protein L5
      during Xenopus oogenesis.
AB  - We studied the pathway of 5S RNA during oogenesis in Xenopus laevis from its
      storage in the cytoplasm to accumulation in the nucleus, the sequence
      requirements for the 5S RNA to follow that pathway, and the 5S RNA-protein
      interactions that occur during the mobilization of stored 5S RNA for assembly
      into ribosomes. In situ hybridization to sections of oocytes indicates that 5S
      RNA first becomes associated with the amplified nucleoli during vitellogenesis
      when the nucleoli are activity synthesizing ribosomal RNA and assembling
      ribosomes. When labeled 5S RNA is microinjected into the cytoplasm of stage V
      oocytes, it migrates into the nucleus, whether microinjected naked or complexed
      with the protein TFIIIA as a 7S RNP storage particle. During vitellogenesis, a
      nonribosome bound pool of 5S RNA complexed with ribosomal protein L5 (5S RNPs) is
      formed, which is present throughout the remainder of oogenesis.
      Immunoprecipitation assays on homogenates of microinjected oocytes showed that
      labeled 5S RNA can become complexed either with L5 or with TFIIIA. Nucleotides 11
      through 108 of the 5S RNA molecule provide the necessary sequence and
      conformational information required for the formation of immunologically
      detectable complexes with TFIIIA or L5 and for nuclear accumulation. Furthermore,
      labeled 5S RNA from microinjected 7S RNPs can subsequently become associated with
      L5. Such labeled 5S RNA is found in both 5S RNPs and 7S RNPs in the cytoplasm,
      but only in 5S RNPs in the nucleus of microinjected oocytes. These data suggest
      that during oogenesis a major pathway for incorporation of 5S RNA into nascent
      ribosomes involves the migration of 5S RNA from the nucleus to the cytoplasm for
      storage in an RNP complex with TFIIIA, exchange of that protein association for
      binding with ribosomal protein L5, and a return to the nucleus for incorporation
      into ribosomes as they are being assembled in the amplified nucleoli.

PMID- 1995393
TI  - Cytological and biochemical analyses of the maternal-effect mutant embryos with
      abnormal cleavage furrow formation in Xenopus laevis.
AB  - We describe an embryonic lethal mutation in Xenopus laevis that provokes
      regression of cleavage furrow formation. The mutant females (designated as af)
      were obtained by the back-cross of a female with one of her sons. All the
      fertilized eggs laid by the mutant females, regardless of the wild-type male used
      in the mating, failed to cleave although each furrow ran at a proper position
      superficially. Light and electron microscopic observations of the embryos
      revealed that the cleavage furrows stayed on the surface and cytoplasmic
      divisions did not take place at all, while nuclear divisions did. Two-dimensional
      gel-electrophoretic comparisons of af and wild-type embryos demonstrated that two
      proteins, having estimated molecular masses of about 38 kDa (pI 6.6) and 78 kDa
      (pI 7.6), were missing in af embryos. Microinjection of clear cytoplasm from a
      wild-type egg into fertilized af eggs provoked partial surface contraction and
      cleavage furrow formation in recipient af eggs. The results showed that the af
      females carry a lethal maternal-effect mutation which causes cleavage furrow
      regression by being deficient in a few proteins, and that cytoplasm of wild-type
      eggs can partially rescue the cleavage furrow formation of af eggs by furnishing
      the corrective material, presumably a product of the normal allele of af.

PMID- 1995394
TI  - Heterotypic and homotypic cellular interactions influencing the growth and
      differentiation of bipotential oligodendrocyte-type-2 astrocyte progenitors in
      culture.
AB  - Cell populations highly enriched in oligodendrocyte-type-2 astrocyte (O-2A)
      progenitors (so defined by their ability to bind the monoclonal antibodies LB1
      and O4, and by the lack of expression of the differentiated glial markers
      galactocerebroside and glial fibrillary acidic protein (GFAP) were obtained from
      rat mixed cortical glial cultures. The O-2A progenitors were grown at low density
      (2 X 10(4) cells/cm2) in BME + 10% fetal calf serum (FCS) on a poly-L-lysine
      (PLL) substrate (controls) or on a substrate of purified type-1 astrocytes (AS)
      killed by air drying (K-AS), in order to analyze the effects of the interaction
      between the two cell types on the growth and differentiation of the immature O-2A
      cells, independently of the mitogenic soluble factors (e.g., platelet-derived
      growth factor; see Raff, 1989, Science 243, 1450-1455) secreted by type-1 AS.
      While on PLL most of the progenitors differentiated into GFAP+ type-2 AS within 1
      week, on K-AS they largely differentiated into GalC+ oligodendrocytes (OL). On
      the latter substrate, however, the precursors achieved a higher density, due to
      higher proliferative activity. The additional observation, that when immature O
      2A cells were seeded at high density (greater than 5 X 10(4) cells/cm2) on PLL
      their differentiation into OL was much more pronounced than in cultures of lower
      density, indicates that there is a close correlation between the density of
      immature O-2A cells and lineage decision, and that the increased OL
      differentiation of the immature O-2A cells on K-AS is at least partly related to
      the higher density achieved by the cells on this substrate. The enhanced
      proliferation of immature O-2A cells on K-AS did not appear to be related to
      platelet-derived growth factor or fibroblast growth factor remaining attached to
      the substrate, nor to known components of the extracellular matrix (ECM), such as
      heparan sulfate, chondroitin sulfate, laminin, or fibronectin, but was probably
      due to other components of a polypeptide nature present in the ECM produced by
      type-1 AS. A cell-free ECM was in fact almost as mitogenic as the K-AS substrate,
      and the mitogenic activities of both K-AS and AS-ECM were similarly inhibited by
      a set of enzymatic (pronase, trypsin) and physicochemical (heat, pH) treatments.

PMID- 1995396
TI  - The B30 ganglioside is a cell surface marker for neural crest-derived neurons in
      the developing mouse.
AB  - We have previously reported the isolation of a monoclonal antibody, mAb B30, that
      recognizes two minor gangliosides specifically expressed in a small subset of
      neurons in the developing mouse central nervous system (Stainier and Gilbert,
      1989). B30 labels mesencephalic trigeminal neurons shortly after differentiation
      until about 2 weeks after birth. Postnatally, it also labels two specific
      monolayers of cerebellar neurons. In this study, we have characterized the B30
      immunoreactivity in the developing peripheral nervous system of the mouse. We
      report that B30 is a marker for neural crest-derived neurons and have used it to
      follow the neuronal differentiation of neural crest cells in a serum-free
      chemically defined culture system. Within hours after plating, neural crest cells
      migrate away from the neural tube explant on a fibronectin or laminin substrate
      and by 24 hr, up to 15% of them have differentiated into morphologically
      identifable neurons. In vitro as in vivo, undifferentiated mouse neural crest
      cells express the GD3 ganglioside which is recognized by mAb B33, and neural
      crest-derived neurons can be labeled by mAbs B33, B30, and also E1.9, a specific
      neuronal cytoskeletal marker. We also show the unique biochemical specificity of
      mAb B30 and provide experimental evidence for the role of the B30 ganglioside in
      the cellular adhesion process.

PMID- 1995395
TI  - Vitamin D and chick embryonic yolk calcium mobilization: identification and
      regulation of expression of vitamin D-dependent Ca2(+)-binding protein, calbindin
      D28K, in the yolk sac.
AB  - The developing chick embryo acquires calcium from two sources. Until about Day 10
      of incubation, the yolk is the only source; thereafter, calcium is also mobilized
      from the eggshell. We have previously shown that during normal chick embryonic
      development, vitamin D is involved in regulating yolk calcium mobilization,
      whereas vitamin K is required for eggshell calcium translocation by the
      chorioallantoic membrane. We have studied here the biochemical action of 1,25
      dihydroxy vitamin D3 in the yolk sac by examining the expression and regulation
      of the cytosolic vitamin D-dependent calcium-binding protein, calbindin-D28K. Two
      types of embryos are used for this study, normal embryos developing in ovo and
      embryos maintained in long-term shell-less culture ex ovo, the latter being
      dependent solely on the yolk as their calcium source. Our findings are (1)
      calbindin-D28K is expressed in the embryonic yolk sac, detectable at incubation
      Days 9 and 14; (2) the embryonic yolk sac calbindin-D28K resembles that of the
      adult duodenum in both molecular weight (Mr 28,000) and isoelectric point, as
      well as the presence of E-F hand Ca2(+)-binding structural domains; (3) systemic
      calcium deficiency caused by shell-less culture of chick embryos results in
      enhanced expression of calbindin-D28K in the yolk sac during late development;
      (4) yolk sac calbindin-D28K expression is inducible by 1,25-dihydroxy vitamin D3
      treatment in vivo and in vitro; and (5) immunohistochemistry revealed that yolk
      sac calbindin-D28K is localized exclusively to the cytoplasm of the yolk sac
      endoderm. These findings indicate that the chick embryonic yolk sac is a genuine
      target tissue of 1,25-dihydroxy vitamin D3.

PMID- 1995397
TI  - Migration of the guinea pig sperm membrane protein PH-20 from one localized
      surface domain to another does not occur by a simple diffusion-trapping
      mechanism.
AB  - The redistribution of membrane proteins on the surface of cells is a prevalent
      feature of differentiation in a variety of cells. In most cases the mechanism
      responsible for such redistribution is poorly understood. Two potential
      mechanisms for the redistribution of surface proteins are: (1) passive diffusion
      coupled with trapping, and (2) active translocation. We have studied the process
      of membrane protein redistribution for the PH-20 protein of guinea pig sperm, a
      surface protein required for sperm binding to the egg zona pellucida (P.
      Primakoff, H. Hyatt, and D. G. Myles (1985). J. Cell Biol. 101, 2239-2244). PH-20
      protein is localized to the posterior head plasma menbrane of the mature sperm
      cell. Following the exocytotic acrosome reaction, PH-20 protein moves into the
      newly incorporated inner acrosomal membrane (IAM), placing it in a position
      favorable for a role in binding sperm to the egg zona pellucida (D. G. Myles, and
      P. Primakoff (1984), J. Cell Biol. 99, 1634-1641). To analyze the mechanistic
      basis for this protein migration, we have used fluorescence microscopy and
      digital image processing to characterize PH-20 protein migration in individual
      cells. PH-20 protein was observed to move against a concentration gradient in the
      posterior head plasma membrane. This result argues strongly against a model of
      passive diffusion followed by trapping in the IAM, and instead suggests that an
      active process serves to concentrate PH-20 protein toward the boundary separating
      the posterior head and IAM regions. A transient gradient of PH-20 concentration
      observed in the IAM suggests that once PH-20 protein reaches the IAM, it is
      freely diffusing. Additionally, we observed that migration of PH-20 protein was
      calcium dependent.

PMID- 1995398
TI  - The Dictyostelium discoideum EB4 gene product and a truncated mutant form of the
      protein are localized in prespore vesicles but absent from mature spores.
AB  - Using polyclonal antibodies directed against two different parts of the predicted
      Dictyostelium prespore protein EB4-PSV, we have investigated the regulation and
      localization of its 58-kDa gene product in wild-type cells and a 31-kDa truncated
      form in the gene disruption transformant A3. In both strains, the protein is
      synthesized during aggregation and is found in the membrane fraction of prespore
      vesicles (PSV). In contrast to other PSV proteins, the EB4 gene product is not
      found in mature spores.

PMID- 1995399
TI  - Developmental arrest at early stages of Chinese hamster embryos homozygous for
      chromosomal rearrangements.
AB  - Forty-three Chinese hamster stocks with autosomal rearrangements produced by X
      irradiation were used. These rearrangements, 38 reciprocal translocations and 5
      inversions, were chromosomally balanced. Heterozygotes for these rearrangements
      were all fertile and morphologically normal in both sexes except for one line
      with growth retardation. By crossing male and female heterozygotes for the same
      rearrangements, homozygotes were obtained in 37 lines. In the remaining 6 lines
      (5 with reciprocal translocations and 1 with an inversion), no homozygotes were
      viable. These 6 lines revealed arrested development of homozygous embryos at the
      two-cell stage, around the eight-cell stage, and after implantation,
      respectively. The bands of the breakpoints of rearrangements associated with
      lethality of homozygous embryos were different for each rearrangement. These
      results suggest that abnormal expression including embryonic lethality in
      homozygotes may be due to an influence of genes at the breakpoints.

PMID- 1995400
TI  - Epithelial control of periotic mesenchyme chondrogenesis.
AB  - Morphogenesis of the cartilaginous otic capsule is directed by interactions
      between the epithelial anlage of the membranous labyrinth (otocyst) and its
      associated periotic mesenchyme. Utilizing a developmental series of high-density
      (micromass) cultures of periotic mesenchyme to model capsule chondrogenesis, we
      have shown that the early influence of otic epithelium in cultures of 10.5- or 14
      gestation day (gd) periotic mesenchyme results in initiation or suppression of
      chondrogenesis, respectively. Furthermore, we have shown that introduction of
      otic epithelium at two distinct times during in vitro development to cultures of
      10.5-gd mesenchyme cells results first in an initiation and then in an inhibition
      of their chondrogenic response. These influences of epithelial tissue on
      chondrogenic differentiation by periotic mesenchyme are not tissue specific but
      are characterized by temporal selectivity. The ability of otic epithelium to
      influence chondrogenesis and the competence of the periotic mesenchyme to respond
      to its signals are dependent upon the developmental stage of both tissues. This
      study provides conclusive evidence that otic epithelium acts as a developmental
      "switch" during otic capsule morphogenesis, signaling first the turning on and
      then the turning off of chondrogenic programs in the responding cephalic
      mesenchyme.

PMID- 1995401
TI  - Gap junctional communication during limb cartilage differentiation.
AB  - The onset of cartilage differentiation in the developing limb bud is
      characterized by a transient cellular condensation process in which
      prechondrogenic mesenchymal cells become closely apposed to one another prior to
      initiating cartilage matrix deposition. During this condensation process intimate
      cell-cell interactions occur which are necessary to trigger chondrogenic
      differentiation. In the present study, we demonstrate that extensive cell-cell
      communication via gap junctions as assayed by the intercellular transfer of
      lucifer yellow dye occurs during condensation and the onset of overt
      chondrogenesis in high density micromass cultures prepared from the homogeneous
      population of chondrogenic precursor cells comprising the distal subridge region
      of stage 25 embryonic chick wing buds. Furthermore, in heterogeneous micromass
      cultures prepared from the mesodermal cells of whole stage 23/24 limb buds,
      extensive gap junctional communication is limited to differentiating cartilage
      cells, while the nonchondrogenic cells of the cultures that are differentiating
      into the connective tissue lineage exhibit little or no intercellular
      communication via gap junctions. These results provide a strong incentive for
      considering and further investigating the possible involvement of cell-cell
      communication via gap junctions in the regulation of limb cartilage
      differentiation.

PMID- 1995402
TI  - A novel M phase-specific H1 kinase recognized by the mitosis-specific monoclonal
      antibody MPM-2.
AB  - At the onset of mitosis, eukaryotic cells display an abrupt increase in a Ca2(+)-
      and cyclic nucleotide-independent histone H1 kinase activity, referred to as
      growth-associated or M phase-specific H1 kinase. The molecular basis for this
      activity is generally attributed to a kinase complex that consists of the p34cdc2
      protein and cyclin, and exhibits maturation-promoting factor (MPF) activity. In
      the present study, we show that more than one kinase contributes to M phase
      specific H1 kinase activity. When mature Xenopus oocyte extract prepared with ATP
      gamma S and NaF was fractionated by gel filtration, two prominent peaks of H1
      kinase activity were detected, with apparent molecular masses of 600 and 150 kDa.
      The 150-kDa kinase copurified with the p34cdc2 protein and was immobilized by the
      suc 1 gene product p13 and anti-cyclin B2, which are specific for the cdc2 kinase
      complex. However, the 600-kDa kinase did not satisfy any of these criteria, thus
      identifying it as a novel M phase-specific H1 kinase. Only the 600-kDa kinase was
      recognized by the mitosis-specific monoclonal antibody, MPM-2, which inhibits
      Xenopus oocyte maturation and immunodepletes MPF activity. Furthermore, not only
      did the full activation of this kinase (MPM-2 kinase) coincide with the
      activation of MPF during the cell cycle, but also MPM-2 kinase-positive fractions
      obtained by gel filtration accelerated progesterone-induced oocyte maturation. It
      is, therefore, likely that MPM-2 kinase is a positive regulator in the M phase
      induction pathway.

PMID- 1995403
TI  - Simultaneous effects of head activator on the dynamics of apical and basal
      regeneration in Hydra vulgaris (formerly Hydra attenuata).
AB  - Previous studies have demonstrated that head activator (HA), an 11 amino acid
      peptide, stimulates head-specific differentiation processes in hydra.
      Additionally, HA enhances the differentiation of interstitial cells into nerve
      cells. This study investigated the effects of exogenous synthetic HA on the
      dynamics of both apical and basal regeneration in a piece of tissue excised from
      the body column of treated animals which comprised one-eighth of the original
      animal. The dynamics of apical and basal regeneration were monitored using the
      monoclonal antibody TS19. This antibody binds to apical and basal ectodermal
      tissue very early in the process of regeneration, before morphological structures
      are evident. Labeling is ultimately localized to the tentacles of the head and a
      ring above the basal disc. Thus, TS19 is a useful tool for analyzing the dynamics
      of both apical and basal patterning processes in the same regenerate
      simultaneously. Quantification of TS19 positive areas on regenerates over a time
      course of 72 hr revealed that HA treatment accelerated and amplified the dynamics
      of both apical and basal TS19 labeling. The specific basal effect was novel and
      was demonstrated to occur in the absence of a determined head independently of
      new nerve cell differentiation. It is proposed that the basal effect was the
      result of growth factor-like activity of HA.

PMID- 1995404
TI  - Involvement of Sarcophaga lectin in the development of imaginal discs of
      Sarcophaga peregrina in an autocrine manner.
AB  - The imaginal discs of Sarcophaga were found not to develop normally in the
      presence of galactose, a hapten sugar of Sarcophaga lectin, or anti-Sarcophaga
      lectin antibody. Wing and leg discs cultured with these substances became
      morphologically abnormal and no imaginal discs reached the stage of terminal
      differentiation, even in the presence of 20-hydroxyecdysone. The development of
      the imaginal discs was shown to be autonomously regulated in an autocrine manner
      by Sarcophaga lectin; namely Sarcophaga lectin was secreted by the imaginal discs
      in the presence of 20-hydroxyecdysone, and the stimulus of self-induced
      Sarcophaga lectin seemed to be indispensable for further development of the
      imaginal discs. Sarcophaga lectin was originally found as a defense protein, but
      these results show that it plays independent roles in both defense and
      development.

PMID- 1995405
TI  - The fast block against polyspermy in fucoid algae is an electrical block.
AB  - Fertilization potentials in Pelvetia fastigiata, Fucus vesiculosus, and Fucus
      ceranoides were studied to examine whether eggs of fucoid algae have an
      electrical block against polyspermy. The resting potential of eggs of all species
      was about -60 mV, depolarizing, respectively, to -24 +/- 5 mV (SD, n = 9) for 7.5
      +/- 2.1 (n = 8) min, -26 +/- 5 (n = 9) mV for 6.4 +/- 2.3 (n = 9) min, and -24 +/
      6 (n = 5) mV for 6.7 +/- 1.9 (n = 4) min. The depolarization was slower, and the
      fertilization potential was about 10 mV more negative in eggs of both F.
      vesiculosus and Pelvetia fertilized in 45-mM Na+ ASW; many of these eggs were
      polyspermic. Steady current was passed through unfertilized eggs of F.
      vesiculosus prior to insemination to test the potential dependence of
      fertilization. Eggs (n = 10) bound sperm at all potentials tested (-45 to -23
      mV), but fertilization was prevented if eggs were held at potentials more
      positive than -45 to -37 mV. Eggs underwent a second depolarization if
      artificially hyperpolarized to potentials more negative than -50 mV immediately
      after the rise of a normal fertilization potential. Thus, fucoid eggs have an
      electrical fast block against polyspermy. Only in F. ceranoides does the
      formation of the cell wall after fertilization appear to be fast enough (i.e., 3
      6 min postfertilization versus at 10-15 min in F. vesiculosus and P. fastigiata)
      to replace the fertilization potential as a polyspermy block. Nonfertilizing
      fucoid sperm swim away from the egg surface by 1-3 min after rise of the
      fertilization potential. This suggests that there is another "intermediate block"
      against polyspermy.

PMID- 1995406
TI  - Temporal lobectomy for the treatment of intractable complex partial seizures of
      temporal lobe origin in early childhood.
AB  - Eleven patients with intractable complex partial seizures underwent temporal
      lobectomy during their first decade. The mean age at onset of epilepsy was two
      years and at surgery was 5.5 years. On the basis of data from clinical
      evaluation, CT, MRI in six patients, and pathological examination of excised
      tissue, the aetiology of the epilepsy was thought to be mesial temporal sclerosis
      in four children, glioma in five, dysplasia in one and chronic progressive
      encephalitis in another. At follow-up eight children were seizure-free, two had
      reduced seizure frequency and only the child with chronic progressive
      encephalitis had not benefitted from surgery.

PMID- 1995407
TI  - Status epilepticus. I: Pathogenesis.

PMID- 1995408
TI  - The role of attention in the regulation of associated movement in children.
AB  - The effect of attentional processes in regulating associated movement was studied
      in 10 male children in each of five age-groups from six to 16 years. They were
      asked to squeeze their index finger and thumb to 75 per cent of their own maximal
      volitional force under three conditions: a spontaneous baseline condition, a
      sensory feedback condition and a post-training condition without sensory
      feedback. Children of all ages were able to reduce the magnitude of associated
      movements during the sensory feedback condition. In the post-training condition
      some of the ability to inhibit was lost, particularly for the six-year-olds. This
      supports the view that the integration of higher order processes, such as
      attention, with lower-level neuromotor inhibitory mechanism, plays a role in the
      reduction of associated movement with increasing age. Implications for therapy
      with clinical populations are discussed.

PMID- 1995409
TI  - Visuomotor performance of normal and clumsy children. I: Fast goal-directed arm
      movements with and without visual feedback.
AB  - The mechanisms underlying accuracy in fast goal-directed arm-movements were
      investigated in normal and clumsy children in two age-groups, six to seven and 10
      to 11 years. Clumsy children in both age-groups had a longer movement time than
      normal children; this difference increased slightly when there was visual
      feedback. For both normal and clumsy children, the relative variability of the
      total distance moved was smaller than that of the distance moved during
      acceleration, indicating a variability reduction mechanism in the course of a
      movement. In the six- to seven-year-old group, the relative variability of the
      distance moved during acceleration and of the total distance was larger for
      clumsy than for normal children; this did not reach significance in the 10- to 11
      year-old group. It is suggested that motor difficulties are linked to inaccuracy
      in open-loop control processes and to less efficient use of visual feedback.

PMID- 1995410
TI  - Effect of food texture on the development of chewing of children between six
      months and two years of age.
AB  - One hundred and forty-three healthy children between six months and two years of
      age were studied to determine the effect of food texture on chewing duration.
      Texture determined very strongly how long a bite of food was chewed, with solids
      taking longest, followed by viscous food and puree, respectively. As children got
      older they became more efficient at chewing a comparable bite of food, i.e.
      chewing time decreased for each texture. Correlations between chewing duration
      and growth measures (length, weight, head circumference) were observed mainly for
      the viscous texture. Growth measures did not significantly influence chewing
      measures. These results differ from previous findings of a strong association
      between weight and eating ability of children with severe eating impairments.

PMID- 1995411
TI  - Reversible quantitative EEG changes in a case of cyclic vomiting: evidence for
      migraine equivalent.
AB  - Medical experts have disputed whether childhood cyclic vomiting is a
      manifestation of epilepsy or a migraine equivalent. Quantitative EEG provides an
      objective measure of changes in brain activity during and between episodes. This
      paper reports reversible changes involving two episodes in a patient whose
      history included cyclic vomiting and emotional/behavioural problems. Abnormal
      delta activity seen during both episodes resolved at follow-up, when the patient
      asymptomatic. The brain wave changes counter the hypothesis that vomiting in
      these patients is psychosomatic, and support the interpretation of cyclic
      vomiting as a migraine equivalent.

PMID- 1995412
TI  - The relationship between language and behaviour.

PMID- 1995413
TI  - Cellular localization and cell cycle regulation by a temperature-sensitive p53
      protein.
AB  - Primary rat embryo fibroblasts were transformed by a p53 mutant (alanine to
      valine change at amino acid 135) plus ras. This p53val135 mutant is temperature
      sensitive for a conformational change detected by the binding of a monoclonal
      antibody, PAb246, which recognizes the wild-type protein or the great majority of
      p53val135 at 32.5 degrees C. At 37 degrees C, both mutant and wild-type p53
      conformational forms co-exist in the cells, while at 39.5 degrees C, the majority
      of the p53val135 in the cell is in a mutant conformation not recognized by PAb246
      antibody. At 39.5 degrees C, the mutant p53 is localized in the cytoplasm of the
      cell. At 32.5 degrees C, the p53 protein enters the nucleus and stops the growth
      of these cells. At 37 degrees C where there is a mixture of mutant and wild-type
      p53, the wild-type p53 protein is in a complex with hsc70 and mutant p53 protein
      in the cytoplasm of the cell during G1. This wild-type protein enters the nucleus
      as the cells enter the S-phase of the cell cycle. At 32.5 degrees C, the cells
      stop replication and arrest at the G1/S border. After 48 hr at 32.5 degrees C,
      91% of the cells are in the G1 fraction of the cell cycle. The S-phase cells
      appear to be immune to the p53 negative regulation of growth until they enter the
      next G1 period.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1995414
TI  - A central role for chromosome breakage in gene amplification, deletion formation,
      and amplicon integration.
AB  - A CHO cell line with a single copy of the DHFR locus on chromosome Z2 was used to
      analyze the structure of the amplification target and products subsequent to the
      initial amplification event. Dramatic diversity in the number and cytogenetic
      characteristics of DHFR amplicons was observed as soon as eight to nine cell
      doublings following the initial event. Two amplicon classes were noted at this
      early time: Small extrachromosomal elements and closely spaced chromosomal
      amplicons were detected in 30-40% of metaphases in six of nine clones, whereas
      three of nine clones contained huge amplicons spanning greater than 50 megabases.
      In contrast, the incidence of metaphases containing extrachromosomal amplicons
      fell to 1-2% in cells analyzed at 30-35 cell doublings, and most amplicons
      localized to rearranged or broken derivatives of chromosome Z2 at this time.
      Breakage of the Z2 chromosome near the DHFR gene, and deletion of the DHFR gene
      and flanking DNA was also observed in cells that had undergone the amplification
      process. To account for these diverse cytogenetic and molecular consequences of
      gene amplification, we propose that chromosome breakage plays a central role in
      the amplification process by (1) generating intermediates that are initially
      acentric and lead to copy number increase primarily by unequal segregation, (2)
      creating atelomeric ends that are either incompletely replicated or resected by
      exonucleases to generate deletions, and (3) producing recombinogenic ends that
      provide preferred sites for amplicon relocalization.

PMID- 1995415
TI  - The protein-coding region of c-myc mRNA contains a sequence that specifies rapid
      mRNA turnover and induction by protein synthesis inhibitors.
AB  - The stability of certain mRNAs is known to be affected by translation. Some mRNAs
      appear to be protected from rapid degradation by translation, whereas degradation
      is coupled to translation for other mRNAs. The molecular determinants of this
      selective effect of translation are unknown. One example of this effect is the
      induction of early-response gene mRNAs in the presence of translation inhibitors.
      To define the molecular basis of induction of early-response gene mRNA expression
      by inhibitors of protein synthesis, we have performed a mutational analysis of
      one member of the early response gene family, the c-myc gene. We find that
      induction by cycloheximide is due to stabilization of c-myc transcripts. The
      requirements for increased expression of c-myc mRNA by cycloheximide are the
      presence of the sequence encoding c-myc amino acids 335-439 on a mRNA that can be
      translated; all other portions of the c-myc gene are dispensable, and this
      sequence can confer induction of mRNA expression by protein synthesis inhibitors
      on a heterologous gene. By direct measurement of mRNA turnover in the absence of
      transcription-blocking drugs, we show that this sequence can function as a
      selective mRNA destabilizing element, that turnover mediated by this element is
      translation dependent, and turnover mediated by this element is inhibited by
      actinomycin D. Our results support the hypothesis that degradation of c-myc mRNA
      is coupled to translation, that the sequences specifying this form of degradation
      are contained in the protein-coding sequence, and that translation inhibitors
      induce expression of c-myc mRNA by blocking turnover mediated by this element.

PMID- 1995416
TI  - Occlusion of the HIV poly(A) site.
AB  - To investigate the selective use of poly(A) sites in the 3' long terminal repeat
      (LTR) but not the 5' LTR of retroviruses, we have studied the poly(A) site of the
      human immunodeficiency virus (HIV-1). Using hybrid HIV/alpha-globin gene
      constructs, we demonstrate that the HIV poly(A) site is inactive or occluded when
      adjacent to an active promoter, either the homologous HIV promoter or the alpha
      globin gene promoter. Furthermore, this occlusion of the HIV poly(A) site occurs
      over a considerable distance of up to at least 500 bp. In contrast, two
      nonretroviral poly(A) sites [alpha-globin and a synthetic poly(A) site] are
      active when close to a promoter. We also show that a short fragment of
      approximately 60 nucleotides containing the HIV poly(A) site is fully active when
      placed at the 3' end of the human alpha-globin gene or within the rabbit beta
      globin gene. This result rules out the requirement of more distant upstream
      elements for the activity of the HIV poly(A) site, as has been suggested for
      other viral poly(A) sites. Finally, we show that the GT-rich downstream region of
      the HIV poly(A) site confers poly(A) site occlusion properties on a synthetic
      poly(A) site. This result focuses attention on this more variable part of a
      poly(A) site in retroviruses as a possible general signal for poly(A) site
      occlusion.

PMID- 1995417
TI  - High-affinity binding sites for the Deformed protein are required for the
      function of an autoregulatory enhancer of the Deformed gene.
AB  - The homeotic selector gene Deformed (Dfd) is required to specify the identity of
      head segments during Drosophila development. Previous experiments have shown that
      for the Dfd segmental identity function to operate in epidermal cells, the Dfd
      gene must be persistently expressed. One mechanism that provides persistent
      embryonic expression of Dfd is an autoregulatory circuit. Here, we show that the
      control of this autoregulatory circuit is likely to be directly mediated by the
      binding of Dfd protein to an upstream enhancer in Dfd locus DNA. In a 25-kb
      region around the Dfd transcription unit, restriction fragments with the highest
      binding affinity for Dfd protein map within the limits of the upstream
      autoregulatory element at approximately -5 kb. A minimal autoregulatory element,
      within a 920-bp segment of upstream DNA, has four moderate- to high-affinity
      binding sites for Dfd protein, with the two highest affinity sites sharing an
      ATCATTA consensus sequence. Site-specific mutagenesis of these four sites results
      in an element that has low affinity for Dfd protein when assayed in vitro and is
      nonfunctional when assayed in embryos.

PMID- 1995418
TI  - Illegitimate recombination in plants: a model for T-DNA integration.
AB  - Agrobacterium tumefaciens is a soil bacterium capable of transferring DNA (the T
      DNA) to the genome of higher plants, where it is then stably integrated. Six T
      DNA inserts and their corresponding preinsertion sites were cloned from
      Arabidopsis thaliana and analyzed. Two T-DNA integration events from Nicotiana
      tabacum were included in the analysis. Nucleotide sequence comparison of plant
      target sites before and after T-DNA integration showed that the T-DNA usually
      causes only a small (13-28 bp) deletion in the plant DNA, but larger target
      rearrangements can occur. Short homologies between the T-DNA ends and the target
      sites, as well as the presence of filler sequences at the junctions, indicate
      that T-DNA integration is mediated by illegitimate recombination and that these
      processes in plants are very analogous to events in mammalian cells. We propose a
      model for T-DNA integration on the basis of limited base-pairing for initial
      synapsis, followed by DNA repair at the junctions. Variations of the model can
      explain the formation of filler DNA at the junctions by polymerase slipping and
      template switching during DNA repair synthesis and the presence of larger plant
      target DNA rearrangements.

PMID- 1995419
TI  - Identification of functional domains in the maize transcriptional activator C1:
      comparison of wild-type and dominant inhibitor proteins.
AB  - Genes encoding fusions between the maize regulatory protein C1 and the yeast
      transcriptional activator GAL4 and mutant C1 proteins were assayed for their
      ability to trans-activate anthocyanin biosynthetic genes in intact maize tissues.
      The putative DNA-binding region of C1 fused to the transcriptional activation
      domain of GAL4 activated transcription of anthocyanin structural gene promoters
      in c1 aleurones, c1 Rscm2 embryos, and c1 r embryogenic callus. Cells receiving
      these constructs accumulated purple anthocyanin pigments. The C1 acidic region
      fused to the GAL4 DNA-binding domain activated transcription of a GAL4-regulated
      promoter. An internal deletion of C1 also induced pigmentation; however,
      frameshifts in either the amino-terminal basic or carboxy-terminal acidic region
      blocked trans-activation, and the latter generated a dominant inhibitory protein.
      Fusion constructs between the wild-type C1 cDNA and the dominant inhibitor allele
      C1-I cDNA were used to identify the amino acid changes in C1 responsible for the
      C1-I inhibitory phenotype. Results from these studies establish that amino acids
      within the myb-homologous domain are critical for transcriptional activation.

PMID- 1995420
TI  - Identification of the recognition sequence for the M.StyLTI methyltransferase of
      Salmonella typhimurium LT7: an asymmetric site typical of type-III enzymes.
AB  - The StyLTI restriction-modification (R-M) system is encoded by chromosomal genes
      of Salmonella typhimurium LT7. We report here the identification of the
      nucleotide (nt) sequence methylated by the StyLTI modification methyltransferase
      (M.StyLTI). This enzyme was partially purified from an Escherichia coli strain
      expressing the cloned M.StyLTI-encoding gene, but lacking StyLTI restriction
      activity, and used to methylate DNAs of known sequence, using S-adenosyl-[methyl
      3H]-methionine as the methyl donor. The [3H]methylated DNA was then digested with
      various endonucleases. Examination of labelled and unlabelled restriction
      fragments allowed us to map the M.StyLTI sites in perfectly defined regions of
      the DNA. Comparison of the nt sequences of DNA segments with or without M.StyLTI
      sites permitted us to identify the asymmetric and nondegenerate pentanucleotide,
      5'-CAGAG-3', 3'-GTCTC-5' as the StyLTI sequence. M.StyLTI was found to methylate
      only the 3' A (see asterisk) in the upper strand of this sequence. Thus, M.StyLTI
      recognises and methylates the DNA in a manner very similar to that of the three
      known type-III MTases, M.EcoPI, M.EcoP15, and M.HinfIII. This strongly suggests
      that StyLTI constitutes a fourth type-III R-M system.

PMID- 1995421
TI  - A vector for directional cloning and expression of polymerase chain reaction
      products in Escherichia coli.
AB  - This paper describes the construction of a modified vector for the cloning and
      expression of protein-encoding genes in Escherichia coli. The vector, pfXblue, is
      derived from the system originally developed by Nagai and Thogerson [Nature 309
      (1984) 810-812], but contains a modified multiple cloning site (MCS) from M13mp18
      to allow directional insertion of foreign coding sequences. The MCS is located
      within the M13mp18 lacZ' gene and thus allows blue/white screening of colonies
      for inserts. The inserted gene is expressed as a fusion protein, which, when
      cleaved by the coagulation factor Xa protease, yields the mature product. This
      vector was successfully used for the production of a mitochondrial [2Fe
      2S]ferredoxin using polymerase chain reaction products generated from a chick
      kidney cDNA library.

PMID- 1995422
TI  - Rapid filter assay for the detection of DNA polymerase activity: direct
      identification of the gene for the DNA polymerase from Thermus aquaticus.
AB  - A method for rapid identification of DNA polymerase activity employing an
      activated DNA substrate covalently bound to nitrocellulose membranes is
      described. Samples containing DNA polymerase are spotted and the membranes are
      incubated in an appropriate polymerization buffer containing radioactively
      labelled dNTPs. By autoradiography of the dried filters, DNA polymerase activity
      can be directly identified. The method can be used for fast and large-scale
      screening of chromosomal expression libraries for heterologous DNA polymerases
      characterized by activity optima different from those of the host organisms. We
      have identified the gene of the thermostable DNA polymerase from Thermus
      aquaticus in an expression library of Escherichia coli.

PMID- 1995423
TI  - Induction of recombinant gene expression in Escherichia coli using an alkaline pH
      shift.
AB  - A commonly used approach to control recombinant protein production in Escherichia
      coli utilizes the lambda pL promoter-operator and the lambda repressor.
      Inactivation of the lambda repressor function allows transcription to proceed.
      However, induction of the RecA-mediated cleavage of lambda repressor by the
      addition of nalidixic acid or inactivation of a temperature-sensitive lambda
      repressor by growth at the nonpermissive temperature can have detrimental effects
      on protein production. This paper describes the use of an alkaline shift in the
      pH of the growth medium that allows expression of genes from the pL promoter in a
      RecA-independent manner. This procedure results in high-level production of
      recombinant protein. The pH shift is performed in the stationary phase of cell
      growth, using culture volumes ranging from 1-1000 ml. This method can result in
      the production of over 15-fold more active protein than when using a temperature
      shift.

PMID- 1995424
TI  - Cloning and overexpression of the gene encoding bacteriophage T5 DNA polymerase.
AB  - T5 DNA polymerase (T5Pol), an essential enzyme for bacteriophage T5 DNA
      replication, is unusual because of its high processivity and strand-displacing
      ability. These two properties in a single polypeptide make T5Pol an ideal
      candidate for structural and functional analysis. Therefore, the structural gene
      encoding the DNA polymerase of bacteriophage T5 (T5pol) has been cloned and
      overexpressed in Escherichia coli. Elimination of sequences upstream from the 5'
      end of the T5pol by exonuclease III digestion was necessary to obtain stable
      clones containing a full-length structural gene. Determination of the nucleotide
      (nt) sequence of the region deleted during clone construction revealed the
      presence of a promoter sequence having extensive homology with known T5 phage
      'early' promoters. By primer extension of mRNA isolated from T5 phage-infected
      cells, two successive G residues located 6 and 7 nt downstream from the -10
      region of this promoter were identified as the initiating nt at the 5' end of
      T5pol mRNA. T5Pol produced in E. coli from the cloned gene under control of a tac
      or phage lambda pL promoter represented as much as 40% of total cell protein. The
      majority of the T5Pol present in extracts of E. coli was insoluble. The amount of
      active enzyme present was estimated to be a maximum of tenfold higher than that
      found in extracts of T5 phage-infected cells.

PMID- 1995425
TI  - Ultraviolet light-induced plasmid-chromosome recombination in Escherichia coli:
      the role of recB and recF.
AB  - Bacterial host cells of different rec genotypes were used to investigate genetic
      requirements of ultraviolet light (UV)-induced homologous plasmid-chromosome
      recombination. Plasmid DNAs which contained a wt or mutant lacY gene were
      irradiated with UV prior to transformation into Escherichia coli host strains
      which contained the complementary lacY allele. Surviving transformants were
      screened to determine the directions of UV-induced recombinational exchange
      between the bacterial and plasmid lacY genes, by assaying lactose utilization.
      Nonreciprocal chromosome-to-plasmid recombination was 100% dependent on the recA
      gene and greater than 80% dependent on the recF gene, but not dependent upon the
      recB gene of E. coli. In contrast, reciprocal plasmid-chromosome recombination
      was strictly dependent on the recA gene, greatly dependent (approx. 80%) on the
      recF gene, and moderately dependent on the recB gene. Nonreciprocal plasmid-to
      chromosome recombination was only induced at very low frequencies, and appeared
      to be moderately dependent on the recB gene, but not dependent on the recF gene.
      UV-induced plasmid-chromosome recombination appeared to proceed by a two-step
      mechanism. In this model, the initial step is recF-dependent, recB-independent,
      and either resolves to become a nonreciprocal chromosome-to-plasmid recombinant,
      or proceeds to the second step. The second step is moderately recB-dependent and
      results in the reciprocal exchange of plasmid-chromosome sequences.

PMID- 1995426
TI  - Cloning of tlrD, a fourth resistance gene, from the tylosin producer,
      Streptomyces fradiae.
AB  - In addition to tlrA, tlrB and tlrC, which were previously cloned by others, a
      fourth antibiotic-resistance gene (tlrD) has been isolated from Streptomyces
      fradiae, a producer of tylosin (Ty), and cloned in Streptomyces lividans. Like
      tlrA, tlrD encodes an enzyme that methylates the N6-amino group of the A2058
      nucleoside within 23S ribosomal RNA. However, whereas the tlrA protein
      dimethylates that nucleoside, the tlrD product generates N6-monomethyladenosine.
      The genes also differ in their mode of expression: tlrA is inducible, whereas
      tlrD is apparently expressed constitutively, and it has been confirmed that the
      tlrA-encoded enzyme can add a second methyl group to 23S rRNA that has already
      been monomethylated by the tlrD-encoded enzyme. Presumably, that is what happens
      in S. fradiae.

PMID- 1995427
TI  - Plasmid cloning vectors that integrate site-specifically in Streptomyces spp.
AB  - Cloning vectors based on the Streptomyces ambofaciens plasmid pSAM2 and the
      streptomycete phage phi C31 were developed for use in Streptomyces spp. These
      vectors replicate in Escherichia coli but integrate by site-specific
      recombination in Streptomyces spp. Both pSAM2-based and phi C31-based vectors
      transformed a number of different Streptomyces spp; however, the phi C31-based
      vectors consistently transformed at higher frequencies than pSAM2-based vectors.
      Southern analysis indicated that the phi C31-based vectors integrated at a unique
      site in the S. ambofaciens chromosome, while the pSAM2-based vectors gave complex
      patterns which could indicate structural instability or use of multiple loci.
      Both types of vectors utilize the apramycin (Am)-resistance gene which can be
      selected in E. coli and Streptomyces spp. with either Am or the commercially
      available antibiotic Geneticin (G418).

PMID- 1995428
TI  - Nucleotide sequence of the fdhE gene involved in respiratory formate
      dehydrogenase formation in Escherichia coli K-12.

PMID- 1995429
TI  - Primary structure of the intergenic region between aceK and iclR in the
      Escherichia coli chromosome.

PMID- 1995430
TI  - Sequence and transcriptional activity of the Escherichia coli K-12 chromosome
      region between rrnC and ilvGMEDA.
AB  - We previously identified a protein related to the expression of the ilvGMEDA
      cluster of Escherichia coli K-12. It was observed that this ilv-related protein
      was produced at higher levels in UV irradiated cells infected with lambda
      dilvGMEDA phage with specific ilvG mutations (ValR), compared to phage carrying
      the wild-type(ValS) ilvG allele. The gene encoding this protein was further
      localized to a region between rrnC and ilvGMEDA by analyzing restriction fragment
      subsets in maxicells. We have now determined the nucleotide (nt) sequence of the
      3.5-kb segment between rrnC and ilvGMEDA, and two open reading frames (ORFs) are
      present in the region expected to contain the ilv-related gene. These ORFs
      predicts Mrs of 18,751 (ORFI) and 20,085 (ORFII) Da, and both ORFs have a strong
      probability to encode proteins based on codon frequency analysis. Maxicell
      analysis revealed that a 1319-bp HindIII-SmaI fragment containing ORFI encodes
      the ilv-related peptide. We deleted a ClaI fragment that removed a portion of
      ORFI encoding the C-terminal region of the peptide, and maxicell analysis
      revealed a decrease in the size of the protein produced in accord with the
      prediction. RNA slot blots and Northern blots were used to characterize
      transcripts encoding ORFI. A transcript initiated 112 nt from the ilvGp2
      promoter, but proceeding in the opposite direction, may encode the ORFI peptide.

PMID- 1995431
TI  - Overproduction and characterization of the iclR gene product of Escherichia coli
      K-12 and comparison with that of Salmonella typhimurium LT2.
AB  - The iclR gene of Escherichia coli K-12, which encodes a regulatory protein
      (repressor) for the aceBAK operon, is located between that operon and metH in the
      91-min region of the chromosome. The iclR gene was cloned and expressed in a
      coupled T7 RNA polymerase/promoter system and the gene product was identified by
      specific binding to a fragment containing the aceBAK operator region. The iclR
      gene product is a polypeptide of 274 amino acids (aa) with a calculated Mr of
      29,741. Comparison of the deduced IclR aa sequence to that of Salmonella
      typhimurium revealed that the two IclR repressors exhibit 89% identity. A
      possible helix-turn-helix motif characteristic of DNA-binding proteins was found
      within the IclR sequence. A search in protein data banks revealed that IclR has a
      score of similarity of 43.7% with GylR, a transcriptional regulator of the
      glycerol operon of Streptomyces coelicolor.

PMID- 1995432
TI  - Cloning the KpnI restriction-modification system in Escherichia coli.
AB  - The genes encoding the KpnI restriction and modification (R-M) system from
      Klebsiella pneumoniae, recognizing the sequence, 5'-GGTAC decreases C-3', were
      cloned and expressed in Escherichia coli. Although the restriction endonuclease
      (ENase)- and methyltransferase (MTase)-encoding genes were closely linked,
      initial attempts to clone both genes as a single DNA fragment in a plasmid vector
      resulted in deletions spanning all or part of the gene coding for the ENase.
      Initial protection of the E. coli host with MTase expressed on a plasmid was
      required to stabilize a compatible plasmid carrying both the ENase- and the MTase
      encoding genes on a single DNA fragment. However, once established, the MTase
      activity can be supplied in cis to the kpnIR gene, without an extra copy of
      kpnIM. A chromosomal map was generated localizing the kpnIR and kpnIM genes on
      1.7-kb and 3.5-kb fragments, respectively. A final E. coli strain was
      constructed, AH29, which contained two compatible plasmids: an inducible plasmid
      carrying the kpnIR gene which amplifies copy number at elevated temperatures and
      a pBR322 derivative expressing M.KpnI. This strain produces approx. 10 million
      units of R.KpnI/g of wet-weight cells, which is several 1000-fold higher than the
      level of R.KpnI produced by K. pneumoniae. In addition, DNA methylated with
      M.KpnI in vivo does not appear to be restricted by the mcrA, mcrB or mrr systems
      of E. coli.

PMID- 1995433
TI  - Elevated intracranial pressure and computed tomography of the brain in fulminant
      hepatocellular failure.
AB  - Cerebral herniation is a leading cause of death in patients with fulminant
      hepatocellular failure. Classical signs of elevated intracranial pressure are
      often absent in these patients. A reliable noninvasive method by which the
      presence of cerebral edema could be determined is much needed. To assess the
      efficacy of computed tomography of the brain in this setting, we compared the
      radiographic findings to the intracranial pressure measured by an epidural
      monitor in patients with fulminant hepatic failure. Unfortunately, a considerable
      difference existed between the presence of cerebral edema diagnosed by computed
      tomography of the brain and elevation of the intracranial pressure. Our
      observations suggest that in patients with fulminant hepatic failure and advanced
      hepatic encephalopathy, computed tomography of the brain is of little value in
      detecting cerebral edema. Pressure monitoring is most important to establish the
      presence and guide the therapy of intracranial hypertension.

PMID- 1995434
TI  - Ultrastructural studies of hepatocyte cytoskeletons of phalloidin-treated rats by
      quick-freezing and deep-etching method.
AB  - We observed hepatocyte cytoskeletons in phalloidin-treated rats by the quick
      freezing and deep-etching method in three dimensions and compared them with the
      ultrastructural findings on conventional ultrathin sections. The numbers of
      microvilli in dilated bile canaliculi were decreased in the rats treated with
      phalloidin for 1 wk. In hepatocytes the cytoplasm around bile canaliculi could be
      divided into three layers, increased microfilament layer, cell organelle layer of
      secretory system and increased smooth surface endoplasmic reticulum layer. In the
      rats treated with phalloidin for 4 wk, microfilaments were extended into the
      cytoplasm near the nucleus in addition to the increased number of large lysosomes
      and microtubules. In both groups, three-dimensional structures of microfilaments
      could be visualized around bile canaliculi and along cell borders by the quick
      freezing and deep-etching method. The branching microfilaments with the diameters
      of 7 to 10 nm were directly attached to other filaments, cell organelles or
      cytoplasmic sides of cell membranes. Moreover, bundled intermediate filaments
      were increased around peribiliary microfilaments associated with long-term
      cholestasis. It is suggested that excessive accumulation of peribiliary
      microfilaments disturb the secretion of bile components into bile canaliculi. The
      cytoskeletal reorganizations of intermediate filaments seem to alter the
      arrangements of various cell organelles.

PMID- 1995435
TI  - Lysosomal and endosomal heterogeneity in the liver: a comparison of the
      intracellular pathways of endocytosis in rat liver cells.
AB  - Air-filled albumin microspheres, asialoorosomucoid and formaldehyde-treated serum
      albumin are selectively taken up by endocytosis in rat liver Kupffer cells,
      parenchymal cells and endothelial cells, respectively. Intracellular transport
      and degradation of endocytosed material were studied by subcellular fractionation
      in sucrose and Nycodenz gradients after intravenous injection of the ligand. By
      using ligands labeled with 125I-tyramine-cellobiose, the subcellular distribution
      of labeled degradation products can be studied because they are trapped at the
      site of formation. The results show that the kinetics of intracellular transport
      are different in hepatic parenchymal, endothelial and Kupffer cells. In
      endothelial cells, the ligand is associated with two types of endosomes during
      the first minutes after internalization and then is transferred rapidly to the
      lysosomes. In parenchymal cells, 125I-tyramine-cellobiose-asialoorosomucoid was
      located in a relatively slowly sedimenting vesicle during the first minute after
      internalization and subsequently in denser endosomes. Degradation of 125I
      tyramine-cellobiose-asialoorosomucoid in parenchymal cells started later than
      that of 125I-tyramine-cellobiose-formaldehyde-treated serum albumin in
      endothelial cells. Furthermore, the ligand seemed to be transferred relatively
      slowly from endosomes to lysosomes, and most of the undegraded ligand was in the
      endosomes. The rate-limiting step of proteolysis in parenchymal cells is probably
      the transport from endosomes to lysosomes. In Kupffer cells, most 125I-tyramine
      cellobiose-microspheres are found as undegraded material in very dense endosomes
      up to 3 hr after injection. After 20 hr, most of the ligand is degraded in
      lysosomes distributed at a lower density than the endosomes in Nycodenz and
      sucrose gradients.

PMID- 1995436
TI  - Zonal differences in ethanol-induced impairments in receptor-mediated endocytosis
      of asialoglycoproteins in isolated rat hepatocytes.
AB  - We have shown previously that ethanol-induced defects in receptor-mediated
      endocytosis of asialoorosomucoid occurred as early as 1 wk after ethanol feeding.
      This study was undertaken as an initial attempt to establish a possible role of
      defective receptor-mediated endocytosis in liver injury by investigating whether
      differences exist in the effects of ethanol on receptor-mediated endocytosis in
      hepatocytes isolated from different regions of the liver. Perivenule cells,
      present in the distal half of the liver, are thought to be more susceptible to
      ethanol-induced liver injury than are the periportal cells located in the
      proximal half of the liver acini. For these studies, we fed male Sprague-Dawley
      rats for 7 days with liquid diets containing either ethanol (36% of calories) or
      isocaloric carbohydrate. Perivenule and periportal hepatocytes were then isolated
      using a digitonin-collagenase perfusion method. In control animals, cells
      isolated from the perivenule region bound significantly more ligand than did
      cells from the periportal region. Amounts of ligand internalized and degraded
      were also greater in perivenule than in periportal cells in these animals. After
      ethanol feeding, cells isolated from both the perivenule and periportal regions
      bound significantly less ligand than their respective controls. This impairment
      in surface and total binding was more pronounced in perivenule than in periportal
      cells. Internalization and degradation of the ligand were also more adversely
      affected in the centrilobular region as shown by decreases of greater than 60% in
      perivenule cells and by only 20% to 30% in periportal cells of ethanol-fed
      animals compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1995437
TI  - Circulating tumor necrosis factor, interleukin-1 and interleukin-6 concentrations
      in chronic alcoholic patients.
AB  - Although altered cytokine homeostasis has been implicated in the pathogenesis of
      alcoholic liver disease, the relationship between cytokines and metabolic
      consequences of alcoholic liver disease is unknown. We, therefore, sought to
      correlate circulating concentrations of tumor necrosis factor-alpha, interleukin
      1 and interleukin-6 to clinical and biochemical parameters of liver disease in
      chronic alcoholic patients. We used an enzyme-linked immunosorbent assay to
      measure plasma tumor necrosis factor and interleukin-1 and a bioassay to measure
      serum interleukin-6 in three groups of alcoholic men as follows: (a) actively
      drinking alcoholic men without evidence of chronic liver disease, (b) nondrinking
      alcoholic men with stable cirrhosis and (c) patients with acute alcoholic
      hepatitis. Mean cytokine concentrations were elevated in cirrhotic patients and
      alcoholic hepatitis patients compared with controls and alcoholic patients
      without liver disease. Tumor necrosis factor-alpha and interleukin-1 alpha
      concentrations remained elevated for up to 6 mo after diagnosis of alcoholic
      hepatitis, whereas interleukin-6 normalized in parallel with clinical recovery.
      Concentrations of all three cytokines were correlated with biochemical parameters
      of liver injury and hepatic protein synthesis plus serum immunoglobulin
      concentrations. We could not demonstrate a relationship between cytokine
      concentrations and peripheral endotoxemia. Percentages of peripheral blood
      monocytes that reacted with monoclonal antibodies to CD25 (interleukin-2
      receptor) and human lymphocyte antigen-DR were similar for alcoholic patients and
      controls. These data suggest that tumor necrosis factor-alpha and interleukin-1
      alpha are related to some of the metabolic consequences of both acute and chronic
      alcohol-induced liver disease, whereas interleukin-6 is related to abnormalities
      seen in acute liver injury.

PMID- 1995438
TI  - Metabolic response of isolated liver cells to in vivo phagocytic challenge.
AB  - This study elucidates the in vivo metabolic response of different liver cells
      after a single phagocytic challenge. In vivo glucose uptake of different tissues
      and isolated liver cells was determined by a sequential double labeling version
      of the 2-deoxyglucose technique. After latex administration, glucose uptake more
      than doubled in the liver, increased by about 50% in the spleen and lung and was
      not changed in muscle and testis. Within 10 min after intravenous injection of
      latex beads, neutropenia developed, with no change in the number of lymphocytes.
      This was accompanied by a marked influx of polymorphonuclear leukocytes into the
      liver. Latex was found in 52%, 35%, and 14% of the isolated Kupffer cells,
      polymorphonuclear leukocytes and endothelial cells, respectively. In vivo glucose
      uptake increased by 111%, 142%, and 43% in these cells. Glucose uptake by the
      latex-free hepatocytes was also elevated, presumably by way of intercellular
      signals between parenchymal and non-parenchymal liver cells. Indomethacin
      pretreatment resulted in the delay of neutrophil immigration into tissues without
      any change in the glucose response of different liver cells. Thus phagocytic
      stimulation in vivo results in marked neutropenia, migration of neutrophils into
      the liver, increased glucose uptake by phagocytic cells of the liver and enhanced
      glucose metabolism by the non-phagocytic parenchymal cells.

PMID- 1995439
TI  - Hepatocellular phenotype in vitro is influenced by biophysical features of the
      collagenous substratum.
AB  - Hepatocytes maintained on different substrata in vitro possess strikingly
      different morphological and biochemical features. Rounded, multicellular
      aggregates of hepatocytes are seen if the cells are plated onto Matrigel, a
      reconstituted basement membrane, whereas a flattened, monolayer of hepatocytes is
      observed with Vitrogen. Hepatocellular protein synthesis is much greater on the
      Matrigel, although collagen biosynthesis appears selectively enhanced on Vitrogen
      grown hepatocytes. We determined that denatured type I collagen could be
      substituted for Matrigel as the substratum, with the hepatocytes remaining the
      same both morphologically and biochemically. This suggested that the cells
      respond to the biophysical state of the extracellular matrix not only to protein
      sequences that determine a binding site. Measurement of steady-state messenger
      RNA levels within cells cultured onto different matrices indicated that the fluid
      substrate of either Matrigel or denatured type I collagen were facilitative for
      induction of cytochrome P-450b/e, which was not seen with the rigid type I
      collagen substrata. In contrast the messenger RNA level for the cytoskeletal
      protein actin was decreased on the fluid matrices, suggesting that the rounded
      cells had a lower requirement for this protein. These findings indicate that
      hepatocytes are responsive to the biophysical state of the extracellular matrix,
      which can lead to significant changes in gene expression by the cells.

PMID- 1995440
TI  - Cyclosporine enhances the growth of carcinogen-induced enzyme-altered foci in rat
      liver.
AB  - Cyclosporine, a powerful immunosuppressant, has been used successfully for organ
      transplantation. Its efficacy on liver transplants of patients with primary
      hepatic tumors remains controversial because of a high rate of recurrence of the
      original tumors in the transplanted livers. In this study, we experimentally
      tested whether cyclosporine exerts any effects on the growth of carcinogen
      initiated liver cells using the short-term assays of rat liver carcinogenesis.
      Dietary cyclosporine, which maintained sufficient levels of blood cyclosporine
      and suppressed host immune functions, enhanced the development of the glutathione
      S-transferase, placental form-positive hepatocyte foci in the liver of male F-344
      rats treated with a single weekly dose of diethylnitrosamine (75 mg/kg) for 3 wk.
      Dietary cyclosporine also accelerated the growth of preformed glutathione S
      transferase, placental form-positive foci induced by a single dose of
      diethylnitrosamine (250 mg/kg) followed by the promoting regimen of a choline
      deficient diet. It is possible that the enhancement of the size of hepatocyte
      foci by cyclosporine could be due to stimulation of growth or inhibition of
      regression. The mechanisms by which cyclosporine modifies the growth of
      preneoplastic lesions in the liver are not yet fully understood. Possible
      involvement of immunologically relevant cells in the liver, Kupffer cells and pit
      cells in the process is suggested.

PMID- 1995441
TI  - Molecular cloning and characterization of an isolate of hepatitis delta virus
      from Taiwan.
AB  - The genomic RNA of an Asian isolate of hepatitis delta virus was cloned from a
      Chinese patient from Taiwan, using the polymerase chain reaction to amplify cDNA
      for cloning and sequencing. The sequence of this hepatitis delta virus isolate
      shares an 86% to 88% similarity with the three published hepatitis delta virus
      RNA sequences, suggesting heterogeneity of hepatitis delta viruses from different
      geographical areas. Four highly conserved, long stretches of sequence were found.
      These four regions corresponded to the sequences required for the autocatalytic
      cleavage activities of the genomic and antigenomic RNAs and the middle and the
      carboxyl terminal parts of the open reading frame for the delta antigen on the
      antigenomic strand. The conservation of nucleotide sequence in these four regions
      was further confirmed by sequencing additional hepatitis delta virus RNAs
      obtained from three patients with chronic delta hepatitis who lived in Los
      Angeles. These findings suggest that the conserved sequences are critical for
      viral replication. These conserved regions offer ideal sites for primer selection
      to carry out polymerase chain reactions to detect hepatitis delta virus RNA in
      patients with hepatitis delta virus infection.

PMID- 1995442
TI  - A rat model of esophageal varices.
AB  - We have developed a new method for inducing portal hypertension and esophageal
      varices in rats--partial ligation of the portal vein after devascularization of
      the circumference of the left renal vein and complete ligation of the portal vein
      on the fifth day thereafter. Thirty rats were separated into groups of 10,
      control (sham operation), complete portal ligation only and complete portal
      ligation plus devascularization. Two weeks after the surgery, the presence of
      esophageal varices in rats with complete portal ligation plus devascularization
      was confirmed by portography and by the histological findings. The diameter (mean
      +/- SD) of the submucosal veins of the lower esophagus in the complete portal
      ligation plus devascularization group (219.4 +/- 86.6 microns) was significantly
      larger than that in the complete portal ligation group (99.8 +/- 53.4 microns) or
      in the control group (30.5 +/- 16.6 microns) (p less than 0.01). Vascular
      structures of the lower esophagus closely resembled those in humans with
      esophageal varices. This new technique is simple, rapid and reliable, and
      application can be made to various experimental studies on portal hypertension.

PMID- 1995443
TI  - Pancreatic pseudocyst in the left hepatic lobe: a report of two cases.
AB  - The ultrasound and computed tomographic imaging features in a rare pancreatic
      pseudocyst of the liver are described in two patients. The pseudocysts occurred
      in the left lobe in both cases, one after a traumatic injury and the other after
      alcoholic pancreatitis. The possible topographical sequences with which
      pancreatic secretions entered the left hepatic lobe to form a cyst are discussed.

PMID- 1995444
TI  - Effects of cytokines on the liver.
AB  - Cytokines are essential for the communication not only between the liver and
      extrahepatic sites but also within the liver itself. Cytokines regulate the
      intermediary metabolism of amino acids, proteins, carbohydrates, lipids and
      minerals. Cytokines partially interact with classical hormones such as
      glucocorticoids, resulting in a complex network of mutual control. Since many
      cytokines exert growth factor-like activities in addition to their specific
      proinflammatory effects, the distinction between cytokines and growth factors is
      somewhat artificial. The liver is an important site of synthesis and the major
      clearance organ for several cytokines. In liver disease, cytokines are involved
      in the onset of intrahepatic immune responses (e.g., during viral hepatitis), in
      liver regeneration (e.g., after partial hepatectomy) and in the fibrotic and
      cirrhotic transformation of the liver such as chronic chemical injury or viral
      infection. Further studies of cytokine actions may lead to a better understanding
      of liver diseases and to the development of new immunomodulating therapeutic
      options.

PMID- 1995445
TI  - DNA integration sites and hepatocellular carcinoma.

PMID- 1995446
TI  - The cloning of cholesterol 7 alpha-hydroxylase: will molecular techniques help us
      understand the physiology of bile acid synthesis?

PMID- 1995447
TI  - Antimicrosomal antibodies: what are they telling us?

PMID- 1995448
TI  - Data watch. What consumers are looking for in orthopedists and otolaryngologists.

PMID- 1995449
TI  - Hospitals tackle image problems at many levels.
AB  - A recent study of consumer attitudes shows that the public's perception of
      hospitals is hazy at best, and experts are warning hospitals to take steps to
      improve hospitals' image. In the following three articles, we examine the
      challenges facing hospitals in different arenas. First, we take a look at the
      consumer survey, which identifies the public's misperceptions about hospitals;
      then we focus on state hospital associations' ongoing efforts to enhance the
      image of hospitals by educating local lawmakers and consumers. Finally, we look
      at the American Hospital Association's ambitious new advocacy program to improve
      the health care community's ability to get its story across to the public and to
      policy-makers.

PMID- 1995450
TI  - Good physician relations key to success of women's centers.
AB  - Women's health centers are opening across the country, fueled by clinical,
      cultural, consumer and marketing factors. But before opening a women's center,
      it's important to consider all the elements that can make such a venture a
      success--or not. Experts say it's important to carry out a philosophy of women's
      health, including a strong patient education component, to complete physician
      recruiting before the center is to open, to hire a director, and to consider the
      gender issues related to staffing. In a related phenomenon, breast health centers
      are gaining attention as a new marketing focus in ambulatory care.

PMID- 1995451
TI  - Supply prices to increase slightly.
AB  - Expect hospital supply prices to increase by about 3 percent to 4 percent during
      1991, says the new economic forecast from the Joint Purchasing Corp. (JPC), New
      York City. JPC's report may help reduce the uncertainty for those making supply
      price forecasts during the current recession. The Economic Forecast and Budget
      Impact Report presents economic information from industry analysts and publishes
      the data in a single volume. The JPC forecast can be used as a guide to help
      determine price changes; however, it's also important to consider changes in
      consumption, utilization, and quality when using the report, says JPC's
      president.

PMID- 1995452
TI  - Case study: managed care helps hospital contain costs.
AB  - Managed care has played an important--if subtle--role in the recent financial
      turnaround of one Houston hospital. The positive results achieved at the 562-bed
      Hermann Hospital led officials there to believe that basic managed care concepts
      can be applied to a hospital setting, though not without an organizational
      overhaul and a careful consideration of internal politics.

PMID- 1995453
TI  - MMBC (Mediplex Medical Building Corp.): building business deals with physicians.
AB  - Nearly one-fifth of the nation's hospitals began work on medical office buildings
      during 1990, according to a recent survey. That's good news for Mediplex Medical
      Building Corp. (MMBC), Dallas, since 95 percent of the buildings that company
      produces house physicians. And as the demand for medical buildings grows, so does
      MMBC. The company will be involved in up to 18 projects during 1991--a 50 percent
      increase over 1990, according to the company's president and CEO.

PMID- 1995454
TI  - Nurse execs see staffs, roles and salaries grow.
AB  - Nurse executives continue to witness an increase in their responsibilities and
      influence, finds a new survey conducted by Witt Associates Inc., Oak Brook, IL,
      and the Association of Nurse Executives (AONE) of the American Hospital
      Association, Chicago. The survey of the senior nurse position within U.S.
      hospitals states that "hospitals are hiring more nurses to cope with a sicker
      patient population and ... are assigning to senior nurse executives larger areas
      of responsibility, especially for outpatient services."

PMID- 1995455
TI  - Hospitals in two cities team up with businesses.

PMID- 1995456
TI  - Physician referral services thrive with proper management.

PMID- 1995457
TI  - Bill would ease insurance costs for small businesses.

PMID- 1995458
TI  - Clinicians: manage your move to manager.
AB  - Clinicians seeking to advance in their careers often look to management
      positions. But making that step from clinician to manager can be a shaky
      proposition if the clinician doesn't apply management savvy to the move.

PMID- 1995459
TI  - Preventive health programs attract industry.
AB  - Soaring health care costs have made prevention programs an attractive prospect
      for corporate America. To survive in the 1990s, Hospitals need to move into the
      preventive services market. If they don't, non-medical corporations will seize
      this opportunity, according to Lawrence T.P. Stifler, Ph.D., president, Health
      Management Resources, Boston.

PMID- 1995460
TI  - Up close: Moise Willis. Interview by Marylyn Harris.

PMID- 1995461
TI  - How hospice nursing helped me choose nursing.

PMID- 1995462
TI  - Technologies of the future: treating a heart attack in the year 2000--what the
      patient can expect.

PMID- 1995464
TI  - There is a reason for dress codes.

PMID- 1995463
TI  - Car rental insurance--do you need it?

PMID- 1995465
TI  - Overview: the life of a nursing student.

PMID- 1995466
TI  - First experience with a patient's death.

PMID- 1995467
TI  - Homeless teenagers on New York City streets.

PMID- 1995468
TI  - David.

PMID- 1995469
TI  - Coat hangers to learning.

PMID- 1995470
TI  - Geriatric clients in crisis.

PMID- 1995471
TI  - With Sally by my side.

PMID- 1995472
TI  - In memoriam. Dorothea Bennett 1929-1990.

PMID- 1995473
TI  - Generation and characterization of an HLA-DR alpha-specific monoclonal antibody
      using L-cell transfectants expressing human and mouse class II major
      histocompatibility dimers.
AB  - Among the HLA-DR-specific monoclonal antibodies (mAbs) that have been
      characterized previously, there is a marked shortage of DR alpha chain-specific
      mAbs which stain unfixed cells. This may result from the high degree of sequence
      similarity between the alpha 1 domains of HLA-DR and H-2E leading to a state of
      cross-tolerance to DR alpha in H-2-expressing mice. BALB/b (E-negative) mice were
      immunized with DR1-transfected mouse L cells. The chain specificity of the
      resulting DR-specific mAb was determined using a panel of transfectants
      expressing hybrid mouse/human class II heterodimers. A DR alpha-specific mAb was
      generated which was capable of immunoprecipitating DR alpha beta dimers and
      inhibiting the anti-DR alloresponse of human T-cell clones. The present study
      demonstrates that, with the selection of a suitable recipient strain,
      transfectants can be useful in the generation and definition of chain-specific
      mouse mAbs.

PMID- 1995474
TI  - Gene responsible for deficient activity of the beta subunit of C8, the eighth
      component of complement, is located on mouse chromosome 4.
AB  - Sera from 73 strains of mice were tested for hemolytic activity through the
      classical and the alternative pathways (CP and AP) in a single radial hemolysis
      assay. Sera from 16 out of 45 laboratory inbred strains had no lytic activity,
      and Ouchterlony analysis with anti-C5 serum showed them to be C5-deficient. Sera
      from 2 out of 28 strains derived from wild mice also had no lytic activity, but
      the C5 molecule was detectable in both. The hemolytic activity of sera from these
      strains can be restored by the addition of partially purified human C8 or human
      serum deficient in C8 alpha-gamma, leading us to conclude that strains M.MOL-MSM
      (MSM) and Mae are deficient in the beta subunit of C8. Typing of (DBA/2J X MSM)F1
      hybrids and of progeny of a backcross to MSM showed that this C8 deficiency is
      controlled by a single recessive gene, designated C8b; the allele with hemolytic
      activity is C8b1; and the allele with no activity C8b0. Because of synteny
      homologies in mouse and human, we looked for and found close linkage between C8b
      and Pgm-2. Typing of recombinant mice for Mup-1 mapped the C8b locus 2.3
      centimorgans (cM) telomeric to Pgm-2 on mouse chromosome 4.

PMID- 1995475
TI  - HLA-D gene studies in relation to immune responsiveness to a grass allergen Lol p
      III.
AB  - The grass pollen allergen Lol p III (Mr 11,000) is a well-characterized antigen
      that has been found useful in immunogenetic studies of human immune
      responsiveness. Since immune responsiveness to this allergen is associated with
      HLA-DR3, we investigated whether there was any sequence in the HLA-D region that
      would render a person "susceptible" [antibody (Ab)-positive] to the allergen. By
      sequence-specific oligonucleotide (SSO) slot-blot and sequence analyses of
      polymerase chain reaction (PCR)-amplified genomic DNA from Lol p III responder
      and nonresponder subjects, Ab responsiveness was found to be strongly associated
      with the sequence Glu-Tyr-Ser-Thr-Ser (EYSTS), present in the first polymorphic
      regions of DR beta I polypeptide chains of DR3, DR11 (split of DR5), and DRw6. Of
      the 41 grass-allergic subjects investigated, 19 had the EYSTS sequence, of whom
      18 (95%) were Lol p III immunoglobulin G (IgG) Ab responders; among the 22 EYSTS-
      subjects, ten were Lol p III responders (P = 0.001, relative risk = 21.6). No
      such association was found with any polymorphic sequences in other DR beta
      chains, or in DQ alpha I and DQ beta I chains. These findings suggest that the
      EYSTS sequence is important in the presentation of an epitope of Lol p III; other
      sequence(s) may be involved in the presentation of other epitope(s). To our
      knowledge, this is the first demonstration of a strong association between a
      specific HLA sequence and immune responsiveness to a well-defined antigen. The
      paper shows that presence of the EYSTS sequence classifies subjects as Lol p III
      responders in 18/19 cases.

PMID- 1995476
TI  - Variable spread of X inactivation affecting the expression of different epitopes
      of the Hya gene product in mouse B-cell clones.
AB  - Cloned B-cell lines from a female T16H/XSxr mouse in which Tdy expression was
      suppressed due to X inactivation and from a male X/XSxr mouse, both of the
      (kxb)F1 haplotype, were examined for H-Y expression. This was determined both by
      their ability to act as targets for H-2k and H-2b-restricted H-Y-specific
      cytotoxic T cells and by their ability to stimulate the proliferation of H-2Kk, H
      2Db (class I) and Ab (class II)-restricted T-cell clones. In B-cell clones from
      the T16H/XSxr mouse, expression of H-Y/Db exhibited partial X inactivation and
      only a proportion (congruent to 30%) of the cells were targets for or stimulated
      H-2Db-restricted H-Y-specific T cells. In contrast, H-Y epitopes restricted by H
      2k (H-Y/Kk, H-Y/Dk) and Ab (H-Y/Ab) exhibited no X inactivation. Furthermore, no
      inactivation of H-Y/Db, H-Y/Ab, or H-Yk was observed in the male X/XSxr mouse.
      These results indicate that the T16H/XSxr female is a mosaic, as a result of the
      variable spread of X inactivation into the Sxr region. They further suggest that
      the H-Y antigen recognized in association with H-2k and H-2Db class I molecules
      and Ab class II molecules may be the product of more than one gene.

PMID- 1995477
TI  - Temporal change in diagnostic criteria as a cause of the increase of malignant
      melanoma over time is unlikely.
AB  - To assess whether the increase in malignant melanoma incidence could be due, at
      least in part, to changes in histological criteria of malignancy, pathologists in
      Australia, France, Italy, New Zealand, Norway, Sweden, the United Kingdom, the
      United States and the USSR reviewed diagnoses of 50 consecutive pigmented naevi
      (40 junctional and compound; 10 intradermal) and 20 consecutive malignant
      melanomas made in each participating centre around 1930, around 1955 and around
      1980. Collaborating pathologists re-read the material, 2,665 cases in all, either
      from the original slide (82%) or from a recut block (17%), gave their diagnosis
      and indicated whether the lesion was benign (B), dubious benign (DB), dubious
      malignant (DM) or malignant (M). As the distribution of review diagnoses was much
      the same whether the original slide or one made from a recut block was read, the
      material was pooled. Overall, 2.8% of cases originally reported as B/DB were
      reviewed as DM/M, while 4.4% of the DM/M diagnoses were held to be B/DB. The
      shifts between categories were greatest around 1955 and least around 1980,
      suggesting increasing uniformity of interpretation. All available blocks were
      recut and sections sent to IARC for review: 1.7% (22) of 1293 B/DB diagnoses were
      considered to be DM/M and 3.3% (18) of 551 DM/M diagnoses were considered to have
      been B/DB. The consistently low frequency of shift in diagnostic category,
      whether the material was reviewed in the collaborating laboratories or by one
      pathologist at IARC, in a study designed to give maximum attention to those
      lesions--the junctional and compound naevi--in which a change in opinion as to
      malignancy would be most likely to arise, suggests that pathologists,
      irrespective of geographical location, are using common criteria. These findings
      argue against changes in histological interpretation as being responsible for
      more than a small portion of the continuous increase of some 3% to 8% per annum
      observed in malignant melanoma incidence. Other explanations, such as an increase
      in the frequency or potential for malignant transformation of precursor lesions,
      must be sought. The anatomical distribution of the malignant melanomas examined
      followed the usual site pattern by sex, and their thickness was observed to
      decrease over the period of the study in most centres.

PMID- 1995478
TI  - Sequence variations in LTR and env regions of HTLV-I do not discriminate between
      the virus from patients with HTLV-I-associated myelopathy and adult T-cell
      leukemia.
AB  - For detailed comparison of human T-cell leukemia virus type I (HTLV-I) in adult T
      cell leukemia (ATL) and HTLV-I-associated myelopathy (HAM), the nucleotide
      sequences of parts of the long terminal repeat (LTR) and env regions of the HTLV
      I proviruses from 12 patients with HAM, 8 patients with ATL and one with both
      diseases were analyzed. About 340 bp of the LTR U3 region, about 450 bp of the 5'
      region and about 280 bp of the 3' region of env were sequenced directly in DNAs
      amplified by the polymerase chain reaction (PCR) with 2 or 3 sets of primers for
      each region. Nucleotide insertions, deletions or point mutations were observed at
      50 positions in these regions of about 1,000 nucleotides length. None of these
      changes was specific to either HAM or ATL, and some changes were observed in
      proviruses from both cases of HAM and ATL. Moreover, the sequences of proviruses
      isolated from pairs of cell lines established from cerebrospinal fluid (CSF) and
      peripheral blood mononuclear cells (PBMCs) of the 4 patients with HAM also had
      different sequences. These results indicate that the proviruses from HAM and ATL
      are indistinguishable in these sequenced regions, suggesting that these 2
      diseases are caused by infection with genetically indistinguishable HTLV-I.
      Therefore, the reason why these two distinct diseases, HAM and ATL, develop in
      HTLV-I carriers may be based on a host factor(s) or some other factor(s) rather
      than variation in the virus itself.

PMID- 1995479
TI  - Ornithine decarboxylase activity and polyamine content in adenocarcinomas of
      human stomach and large intestine.
AB  - Ornithine decarboxylase (ODC) activity and differential polyamine composition
      have been studied in macroscopically normal mucosa, adjacent mucosa, and
      neoplastic tissue of 95 patients with adenocarcinomas of stomach and large
      intestine. In tumors, we found increased ODC activity and polyamine content as
      compared with surrounding mucosa. ODC activity in macroscopically normal tissue
      of patients with tumors of stomach and large intestine increased as the disease
      progressed. An inverse relationship was observed between ODC activity in
      adenocarcinomas and differentiation.

PMID- 1995480
TI  - The decline in the incidence of stomach cancer in Sweden 1960-1984: a birth
      cohort phenomenon.
AB  - Trends in the incidence of stomach cancer among 52,604 patients notified to the
      National Swedish Cancer Registry in 1960 through 1984 were analysed. Age
      standardized incidence rates declined throughout the period, from 47.1 to 24.6
      per 10(5) in males and from 23.8 to 12.7 per 10(5) in females. Among males the
      decline in incidence was more pronounced in younger age strata, 35-54 years,
      while in females it reached a maximum at ages 70-74 years. In a multivariate
      analysis the age-cohort model adequately represented the data and there was no
      reason to separate the effects of the full age-period-cohort model. Compared with
      the cohort born in 1876-1884, the relative risk of developing stomach cancer was
      0.46 (95% CI:0.44-0.48) in males and 0.39 (95% CI:0.37-0.42) in females born in
      1906-1914. This supports the view that the declining incidence is due to a change
      in the exposure of the population to aetiological factors of stomach cancer and
      not to refinement of the diagnosis and classification of abdominal tumours. The
      results also imply that exposure to aetiological factors early in life together
      with a long induction period is of importance in the development of stomach
      cancer.

PMID- 1995482
TI  - Altered dosage of the sex chromosomes in human testicular cancer: a molecular
      genetic study.
AB  - Thirty-one males with testicular germ-cell tumors were studied by Southern
      hybridization using X- and Y-chromosome-specific probes as well as a
      pseudoautosomal probe. Densitometric analysis showed changes in the relative
      dosage of Y-chromosomal fragments in tumor DNA from 12 out of 31 patients (39%)
      as compared to normal DNA from the same patients. In 11 tumors the relative
      intensity ratios of Y-chromosome-specific fragments had decreased from the normal
      value of 1 to values between 0 and 0.77. An increase in the Y-chromosomal dosage
      was observed in 1 case. The entire Y chromosome was apparently involved in most
      patients but 2 tumors revealed regional variation. Tumor DNA of 2 patients with Y
      chromosomal deficiency showed a concomitant increase in the X chromosomal dosage.
      The pseudoautosomal region that is shared by both sex chromosomes was involved in
      a total of 8 tumors (26%), 2 of which did not show any obvious dosage changes
      with probes detecting strictly X- or Y-chromosome-specific fragments. Autosomal
      alterations in the present tumor series have been described. A dosage change
      involving the sex chromosomes accompanied loss of heterozygosity at loci in 3p or
      11p in 10 tumors out of 15 (67%). Seminomas tended to be affected more often than
      non-seminomas by either type of alteration. Our results indicate that changes in
      the sex chromosomes occur in a substantial proportion of male germ-cell tumors
      and, together with other defects, may constitute an important step in tumor
      development and/or progression.

PMID- 1995481
TI  - Risk factors for penile cancer: results from a case-control study in China.
AB  - An epidemiologic study of penile cancer involving 141 cases and 150 community
      controls was undertaken in a high-risk area in China. Personal interviews, as
      well as physical examinations among the prospectively ascertained subjects,
      enabled evaluation of a variety of potential risk factors. Strongly related to
      risk were conditions restricting the motility of the foreskin, including phimosis
      or paraphimosis, particularly when so severe that circumcision was used for
      treatment. Poor hygiene practices also appeared to increase risk, particularly as
      evidenced by detection of smegma on physical examination, although it was
      difficult to decipher whether this association was etiologic or merely a
      consequence of disease. A sexual relationship outside of marriage was associated
      with a RR of 1.7, and appeared to be a more important discriminator than number
      of lifetime sexual partners. Risk was increased among subjects reporting previous
      genital conditions, particularly sexually transmitted diseases, and physical
      examinations revealed the appearance of genital warts among 13 cases vs. I
      control. Interviews with wives of study subjects failed to provide evidence of a
      "female factor" in the etiology of penile cancer. This study supports the need
      for further evaluation of the role of hygiene and sexually transmitted agents in
      the etiology of penile cancer.

PMID- 1995483
TI  - EGF in breast cyst fluid: relationships with intracystic androgens, estradiol and
      progesterone.
AB  - The relationship between intracystic levels of epidermal growth factor (EGF) and
      those of dehydroepiandrosterone sulphate (DHEA-S), delta-4-androstenedione (delta
      4-A), 17-beta-estradiol (17-beta-E) and progesterone (PROG) have been studied in
      77 breast cyst fluid (BCF) samples. EGF and all tested hormones appeared to be
      inversely correlated with the intracystic Na+/K+ ratio (p less than 0.001).
      Consequently, when the BCFs were subdivided according to the Na+/K+ ratio,
      significantly higher levels of EGF, DHEA-S, delta-4-A, 17-beta-E and PROG were
      found in Na+/K+ less than 3 BCFs compared with Na+/K+ greater than 3 BCFs (p less
      than 0.001 in all cases). Strong direct relationships were found among all
      steroid hormones when they were correlated to one another (p less than 0.001).
      Intracystic EGF concentration was directly and significantly correlated with each
      tested hormone (p less than 0.001). However, the relationship between EGF and
      steroid hormones appeared to be different in the 2 BCF types (Na+/K+ less than 3
      or greater than 3).

PMID- 1995484
TI  - Heterogeneity for integrin expression and cytokine-mediated VLA modulation can
      influence the adhesion of human melanoma cells to extracellular matrix proteins.
AB  - Expression of alpha and beta subunits of VLA and VNR integrins was analyzed by
      cytofluorimetric analysis on 6 different human primary and metastatic melanoma
      cell cultures. Marked inter-tumor heterogeneity was observed, and expression of
      VLA-alpha I, VLA-alpha 2 and VLA-alpha 6 was lower on primary melanomas than on
      metastatic lesions. The function of VLA products on melanoma cells was assessed
      by adhesion assays to extracellular matrix (ECM) proteins using a panel of
      melanoma clones previously characterized for the presence and heterogeneity of
      expression of the distinct VLA-alpha subunits. These experiments indicated that
      intra-tumor heterogeneity in the integrin profile can influence the interaction
      of neoplastic cells with ECM proteins. Inhibition of adhesion with antibodies to
      VLA-alpha subunits revealed that the presence on melanoma cells of VLA-alpha 2,
      VLA-alpha 5 and VLA-alpha 6 is relevant for the adhesion to type-IV collagen,
      fibronectin and laminin respectively. Culture of tumor cells in the presence of
      cytokines such as rIL-I beta, rTNF-alpha, rIFN-gamma or TGF-beta I could induce
      up- or down-modulation in the level of expression of multiple VLA integrins.
      Cytokine-mediated antigenic shifts in the VLA profile of melanoma cells were
      detected by cytofluorimetric analysis as early as 24 hr after cytokine exposure.
      The cytokine-dependent change in the matrix receptor profile of melanoma cells
      also affected the adhesion to ECM proteins as revealed by the enhanced adhesion
      of rTNF-alpha-treated cells to fibronectin. These data indicate that constitutive
      heterogeneity in the integrin profile or cytokine-mediated shifts in VLA
      expression can affect the ability of human melanoma cells to interact with
      different ECM components.

PMID- 1995485
TI  - Immunotherapy of a mouse mammary carcinoma by sustained peritumor release of IL
      2.
AB  - The purpose of this study was to compare the local and systemic therapeutic
      effects of Interleukin-2 (IL-2) used in 3 different preparations: suspended in
      PBS, suspended in 2% agar, and entrapped in multi-lamellar liposomes suspended in
      2% agar. The liposomes were composed of phosphatidylglycerol and
      phosphatidylcholine in a 1:4 molar ratio. The net release of IL-2 in vitro (by
      ELISA assay) at 37 degrees C, measured at 4 hr, 2 days, and 10 days, was 50%,
      75%, and 100% from agar, and 8%, 22%, and 33% from liposomes in agar. In the
      therapeutic tests, the IL-2 preparations were injected close to s.c. implants of
      the MC2 mouse mammary carcinoma. Four injections at weekly intervals of IL-2 in
      agar had as much local and systemic (against uninjected contralateral tumor
      implants in treated mice) therapeutic effect as the same total amount of IL-2 in
      PBS given in 20 daily injections over 4 weeks. The IL-2 liposome-gel preparation
      was most effective (p less than 0.05), probably due to the more sustained release
      of IL-2. Three injections of this preparation gave a fixed and sustained
      peritumor release of IL-2 which, at sub-toxic levels, resulted in both local and
      systemic therapeutic effects.

PMID- 1995486
TI  - The role of the Peyer's patch in the carcinogenesis of lymphoid cells.
AB  - The dose response to 3-methylcholanthrene (3-MC), the promoter effects of
      2,6,10,14-tetramethylpentadecane (pristane) and the target-organ specificity in
      the preferential induction of B-lymphoid malignancies versus thymic tumors were
      examined. Lymphoid malignancies were induced in approximately 30% of the
      Copenhagen rats treated with injections in Peyer's patches (PP) of low,
      intermediate or high doses of 3-MC. A low dose of 3-MC induced B-lymphocytic
      leukemias or B lymphomas, whereas thymic tumors were detected in rats treated
      with high doses. Co-treatment of rats with pristane and 3-MC resulted in
      increased incidences and decreased latency of the lymphoid malignancies observed,
      suggesting that pristane acts as a tumor promoter. To address the possible role
      of PP in the induction events, PP were surgically removed after 3-MC treatment
      and the remaining small intestine anastomosed. Thymic tumors, but no B-lymphoid
      malignancies, were observed, indicating that the PP environment was important in
      the induction of the B-lymphoid malignancies. Radiotracer studies also revealed
      that appreciable amounts of 3-MC were disseminated to the thymus within 24 hr
      after treatment of PP with a high dose of 3-MC. Furthermore, direct intrathymic
      injection of the thymus with 3-MC resulted in the development of thymic tumors
      only. These results support the hypothesis that the PP has an important role in
      early events in the carcinogenesis of B lymphocytes and in the dissemination of 3
      MC to the thymus.

PMID- 1995487
TI  - Human colon carcinoma, fibrosarcoma and leukemia cell lines produce tumor
      associated trypsinogen.
AB  - Previous studies have indicated that cyst fluid of ovarian tumors contains 2
      trypsinogen isoenzymes, called tumor-associated trypsinogen-I (TAT-I) and
      trypsinogen-2 (TAT-2), the levels of which correlate with the degree of
      malignancy of the tumors. In addition, these cyst fluids contain large amounts of
      tumor-associated trypsin inhibitor (TATI), which is also expressed in many other
      human tumors. In the present study we examined the production of TAT-I, TAT-2 and
      TATI in 9 established tumor-cell lines. TAT-2 was produced by 5 cell lines. Its
      concentration in the conditioned medium of COLO 205 colon adenocarcinoma cells, K
      562 erythroleukemia cells and fibrosarcoma cell lines HT 1080, 8387 and A 9733
      was 460 micrograms/l, 9.8 micrograms/l, 21 micrograms/l, 8.8 micrograms/l and
      0.24 micrograms/l, respectively. TAT-I was detectable in the conditioned medium
      of COLO 205 and HT 1080 cells at concentrations of 64 micrograms/l and 0.5
      micrograms/l, respectively. TATI was detected only in the media of COLO 205 cells
      at a concentration of 23 micrograms/l. TAT-2 zymogen was purified from the
      conditioned medium of COLO 205 and HT 1080 cells by immunoaffinity
      chromatography. According to its aminoterminal amino acid sequence, a molecular
      mass of 28 kDa by SDS-PAGE, elution pattern in ion-exchange chromatography and
      ability to be activated by enteropeptidase, the zymogen is identical to that
      previously isolated from cyst fluid of ovarian tumors. In addition, we found that
      TAT-2 secretion could be down-regulated by dexamethasone in HT 1080 cells but not
      in COLO 205 cells. The abundant production of TAT-2 isoenzyme in different cancer
      cell lines suggests that it could contribute to the increased proteolytic
      activity of many human tumors.

PMID- 1995488
TI  - The effect of radiosensitizers on radio-immunotherapy, using 131I-labelled anti
      CEA antibodies in a human colonic xenograft model.
AB  - Anti-CEA antibodies were used for radio-immunotherapy in an established LS174T
      colonic xenograft in nude mice. A single IV dose of either 131I-PK4S (polyclonal)
      or -A5B7 (monoclonal) antibody produced tumour regression, and significantly
      delayed subsequent tumour growth. Administration of a clearing second antibody,
      24 hr post 131I-PK4S and at 5 times the dose, significantly reduced the
      therapeutic effect of radio-antibody alone. Tumours of mice given non-specific
      antibody or unlabelled anti-CEA antibody grew like those of untreated controls.
      In an attempt to enhance therapy without increasing dose, radiosensitizers
      normally employed with external beam radiation were used in combination therapy.
      When the hypoxic cell radiosensitizer misonidazole was combined with 131I-A5B7,
      it significantly prolonged tumour-growth inhibition over radio-antibody alone.
      Conversely, the therapeutic effect of either radio-antibody was significantly
      reduced when used in combination with the halogenated pyrimidine radiosensitizer
      5-iododeoxyuridine. Neither sensitizer alone affected tumour growth.

PMID- 1995489
TI  - Inhibition of respiration of tumor cells by methylglyoxal and protection of
      inhibition by lactaldehyde.
AB  - The effect of methylglyoxal (MG), ascorbic acid and lactaldehyde has been tested
      on the in vitro respiration of Ehrlich ascites carcinoma (EAC) cells and several
      normal and malignant human tissues. Methylglyoxal inhibited the respiration of
      each type of malignant cell and tissue tested, but it had practically no
      inhibitory effect on the respiration of any of the normal cells and tissues.
      Ascorbic acid exhibited a synergistic effect with MG in inhibiting the
      respiration of all the neoplastic cells. In the presence of lactaldehyde, a
      catabolite of MG, the inhibitory effect of MG on the respiration of tumor cells
      was significantly reduced. Lactaldehyde can exert a similar protective effect on
      the loss of viability and transplantability of MG-treated EAC cells.

PMID- 1995490
TI  - Activation of ras oncogenes and expression of tumor-specific transplantation
      antigens in methylcholanthrene-induced murine fibrosarcomas.
AB  - The DNA of 22 fibrosarcomas, newly induced in BALB/c mice by subcutaneous doses
      of 3-methylcholanthrene (3-MCA), was tested in NIH 3T3 transformation assay.
      Activation of K-ras and N-ras was found in 7 and 3 cases respectively. No H-ras
      activation was detected. Polymerase chain reaction and oligonucleotide
      hybridization performed on the DNA of the 22 sarcomas revealed 5 cases of K-ras
      mutation at codon 12, 3 at codon 13 and 1 at both codons. One case of K13
      mutation was not detectable by transfection. Three cases of mutation at codon 61
      of N-ras were also found, one of which was simultaneous with a K12 mutation.
      Tumor-specific transplantation antigens (TSTA) were assessed in the 22 original
      tumors. Altogether 16 sarcomas were immunogenic, with the highest frequency of
      TSTA+ tumors (10/11 and 5/6) in the groups given 1.0 and 0.1 mg of 3-MCA
      respectively, the lowest (1/5) in that with 0.01 mg of carcinogen; ras mutations
      occurred in the DNAs of 11 out of the 16 TSTA+ sarcomas, but none of the DNAs of
      the 6 TSTA- tumors showed ras mutation. The results suggest that 3-MCA-induced
      transformation of subcutaneous fibroblasts can involve mutations in codons 12, 13
      or 61 of K- and N- but not H-ras gene and that such mutation is accompanied by
      the expression of TSTA.

PMID- 1995491
TI  - Tumor regression and induction of anti-tumor immunity by local chemotherapy of
      guinea-pigs bearing a line-10 hepatocarcinoma.
AB  - Local administration of a low dosage of the active cyclophosphamide derivative 4
      hydroperoxy-cyclophosphamide (4-HPCY) at the site of antigenic stimulation
      strongly enhances T-cell-mediated immune responses in both mice and guinea-pigs.
      Such immunopotentiation is related to functional elimination of suppressor cells
      from the draining lymph nodes. In the present study we examined the potential
      immunotherapeutic effects of local cytostatic drug administration in strain-2
      guinea-pigs bearing a line-10 hepatocarcinoma. This tumor, when injected
      intradermally (10(6) cells) metastasizes within 7 days into the draining lymph
      node and untreated animals die within 60-80 days from metastatic growth. In
      sensitization experiments, using irradiated line-10 tumor cells, potentiation of
      delayed-type hypersensitivity reactivity was observed with local administration
      of low dosages of 4-HPCY. Intralesional treatment with increasing dosages of 4
      HPCY, when started 7 days after tumor-cell inoculation and continued for 3 weeks,
      resulted in a dose-dependent regression of the primary tumor. Cure rates of up to
      75% were achieved. All cured animals showed strong delayed-type hypersensitivity
      reactivity towards line-10 cells and were resistant to a rechallenge with 10(6)
      line-10 tumor cells. When treatment was started at a very late stage of the
      disease (day 14) only a small number of animals were cured. However, when local
      chemotherapy was preceded by one (non-curative) systemic dose of
      cyclophosphamide, a 57% cure rate was obtained. Again, all cured animals showed
      strong delayed-type hypersensitivity reactivity and protective immunity to line
      10 tumor cells. Tumor immunity was transferable to naive recipients with immune
      spleen cells and was T-cell-dependent. Other cytostatic drugs, selected for local
      immunopotentiating capacity, notably etoposide (VP16) and cis-platinum (cis-Pt)
      were similarly effective in the local chemotherapy protocol.

PMID- 1995492
TI  - Fructose-1,6-diphosphatase deficiency in Israel.
AB  - The clinical and biochemical data on nine patients belonging to six families with
      fructose-1,6-diphosphatase deficiency are reported. Two of the six families were
      Jewish, three were Moslem Arabs and one was of Druze origin. All patients had had
      neonatal hypoglycemia, lactic acidosis and an abnormal fructose or glycerol
      loading test. At a later age, instances of hypoglycemia occurred in patients both
      with and without preceding illness. Hypoglycemic attacks were associated with
      severe hyperuricemia and metabolic acidosis. Therapeutic measures included a
      restriction in fructose intake and avoidance of prolonged fasting, particularly
      during febrile episodes.

PMID- 1995493
TI  - Catecholamine determination in sequential urine voiding: a method for detecting
      pheochromocytoma in patients without elevated urinary catecholamines.
AB  - The biochemical diagnosis of pheochromocytoma is based on the demonstration of
      increased amounts of catecholamines, or catecholamine metabolites, in 24-h urine
      samples. In patients whose 24-h urine catecholamines are within normal limits,
      and in whom short duration catecholamine elevations are suspected, timed urine
      collections have been used to detect these elevations. In this study,
      determination of catecholamines in sequential urine voidings and consideration of
      their relative values are suggested as a further method to detect
      pheochromocytomas, especially in cases without extended elevation of urinary
      catecholamine levels. The use of this method is demonstrated in three cases in
      which pheochromocytoma would not otherwise have been proven by laboratory
      determination.

PMID- 1995494
TI  - Fever and chills caused by nitrofurantoin taken after sexual intercourse.
AB  - Nitrofurantoin is one of many antibiotics used in the treatment of urinary tract
      infections (UTI). The drug is also used for the prevention of recurrent UTI in
      women. We report a case of nitrofurantoin drug fever associated with its use,
      following sexual intercourse, for chemoprophylaxis of UTI. The intermittent
      appearance of the side effects due to the occasional use of antibiotics, such as
      in this case, may easily lead to misdiagnosis.

PMID- 1995495
TI  - Measles containment in Israel.
AB  - Despite the availability for more than two decades of an effective vaccine
      against measles, major outbreaks in Israel have occurred in recent years and can
      be expected to occur in the future because large numbers of children have never
      been vaccinated against the disease. The main public health challenge should be
      to locate and vaccinate those children aged 16 months to 5 years who have never
      been vaccinated, since it is among these children that incidence, complications
      and mortality are highest. Although a second routine measles vaccination to
      schoolchildren will decrease the number of susceptibles, this new program feature
      will not eliminate outbreaks and must not be allowed to divert attention from the
      essential target group.

PMID- 1995496
TI  - Prevention of measles in Israel: short- and long-term intervention strategies.
AB  - Measles morbidity and mortality have declined in Israel since the introduction of
      routine vaccination in 1967. The reported incidence of civilian cases of measles
      declined from 50/100,000 in 1968-72, to 27/100,000 in 1983-87. There was also a
      decrease from 108 to 49 measles deaths, and from 84 to 29 cases of subacute
      sclerosing panencephalitis in these respective periods. The measles epidemic in
      1982 included 7,864 reported civilian cases with an additional 3,000 cases in the
      Israel Defense Forces. The 1985-86 epidemic included 4,956 reported civilian
      cases. Current immunity levels leave large numbers (15-20%) of children and young
      persons susceptible to the disease and its transmission. Despite the long
      standing childhood immunization program, the goal of complete control over and
      elimination of the disease will not be achieved in the near future by current
      immunization policies. The 3-4 year cycle of measles epidemics may be expected to
      cause large-scale morbidity and some mortality in the 1990-92 period. Short- and
      long-term measles control policies for this preventable disease are discussed.

PMID- 1995497
TI  - Mortality trends among Jewish and non-Jewish women in Israel, 1960-82.
AB  - Until 1975 in Israel mortality rates in women aged greater than or equal to 25
      years old were higher among Jewish women than non-Jewish women. Since then the
      relationship has been reversed with higher rates in the non-Jewish group. The
      three main causes of death in the two groups were heart disease, cancer and
      cerebrovascular disease (CVA). The proportional mortality and death rates from
      total heart diseases rose in the non-Jewish population during 1970-82, whereas in
      Jewish women there were only slight changes. With regard to cancer, the
      proportional mortality and death rates were higher in the Jewish group. However,
      from 1970 to 1982 cancer mortality in the Jewish population declined
      continuously, while in the non-Jewish group it rose. Mortality from CVA rose in
      both Jewish and non-Jewish women until 1974, but then declined. Since then, the
      rates remained considerably higher in the non-Jewish population. Death from heart
      disease, cancer and CVA can partially explain the reversal in total mortality
      rates in 1975.

PMID- 1995498
TI  - Mortality trends among Jewish and non-Jewish men in Israel, 1960-82.
AB  - Until 1975 in Israel the mortality rates in men greater than or equal to 25 years
      old were higher in Jews than non-Jews. Since then the relationship has been
      reversed with higher rates in the non-Jewish group. The three main causes of
      death in the two groups were heart disease, cancer and cerebrovascular disease
      (CVA). Death rates from total heart diseases rose in the non-Jewish population
      during 1970-82, whereas in the Jewish men there were only slight changes. With
      regard to cancer, death rates were higher in the Jewish group, but from 1970 to
      1978 it increased in both groups, the change being relatively higher in non-Jews.
      Mortality from CVA was higher among Jews at the beginning of the study period,
      but since 1978 the rates remained higher in the non-Jewish population. Death from
      heart disease, cancer and CVA can partially explain the reversal in total
      mortality rates in 1975. A comparison of the data of Israeli men with those of
      Israeli women shows that the mortality rates of the non-Jewish population of both
      sexes have changed dramatically over the last decade. These findings have
      important implications for the planning of further research and for priority
      determination in health care planning.

PMID- 1995499
TI  - Importance of dog control in preventing human post-exposure rabies prophylaxis in
      southern Israel.

PMID- 1995500
TI  - Mitral valve prolapse and thromboembolic brain disease.

PMID- 1995501
TI  - Epidemiology of measles in the vaccination era: implications for an effective
      prevention of the disease.

PMID- 1995502
TI  - Mitral valve prolapse in young Israelis with thromboembolic brain disease.
AB  - In order to establish the association between mitral valve prolapse (MVP) and the
      incidence of thromboembolic disease of the brain we reassessed 36 patients (less
      than or equal to 50 years old) who were hospitalized during 1983-85 because of
      cerebrovascular accidents. The patients underwent complete physical and
      neurological examinations, blood tests including coagulogram and two-dimensional
      echocardiogram. The control group comprised 117 patients without cerebrovascular
      events. In the study group, 4 patients (11.1%) had MVP compared with 10 (8.5%) in
      the control group. Of these four, only one male did not have any risk factor for
      thromboembolic event; among the other three the risk factors were systemic lupus
      erythematosus, hyperlipidemia, diabetes, hypertension and pregnancy. We conclude
      that our results are in accordance with most of the literature that MVP is not a
      risk factor for thromboembolic disease except in Greek and Italian populations,
      which are ethnically more homogeneous than other Western societies studied.

PMID- 1995503
TI  - The fragility of mortality data in epidemiologic research.

PMID- 1995504
TI  - Role of tumor necrosis factor in the pathogenesis of intravascular coagulopathy
      of sepsis: potential new therapeutic implications.
AB  - Tumor necrosis factor (TNF) induced by bacterial lipopolysaccharide (LPS) was
      shown to have an important role in precipitation of septic shock and disseminated
      intravascular clotting (DIC). At the endothelial level TNF down-regulates
      thrombomodulin (thus preventing protein C formation) and inhibits the production
      of tissue plasminogen activator (t-PA), thus impairing anticoagulant mechanisms.
      On the other hand, TNF up-regulates the production of procoagulant factors such
      as t-PA inhibitor (PAI), tissue factor and platelet activating factor (PAF).
      These effects create an imbalance between procoagulant and anticoagulant
      mechanisms, in favor of the former. TNF also activates polymorphonuclears (PMNs),
      and increases their chemotaxis and adherence to endothelial surfaces by up
      regulation of specific endothelial (ELAM-1) and PMN (CDw18) adherence proteins.
      The damage inflicted by activated PMN to the endothelial cell promotes tissue
      factor exposure and PAI release, with initiation of the characteristic explosive
      coagulation process of DIC, facilitated by the dissociation between pro- and
      anticoagulant mechanisms induced by TNF. These newly discovered mechanisms
      precipitating septic shock and DIC enable consideration of new treatments for
      this condition as anti-TNF antibodies or TNF inhibitors, anti-ELAM-1 antibodies
      anti-tissue factor antibodies, administration of activated factor C, etc. These
      therapeutic approaches may revolutionize the treatment of septic shock and DIC in
      the next decade.

PMID- 1995505
TI  - Computerized tomographic recognition of visceral pleural changes.
AB  - Pathology of the visceral pleura seen by CT of the lung can be separated from the
      underlying lung parenchyma by using appropriate CT window viewing settings. A
      wide window setting permits both pleura and lung parenchyma to be examined
      simultaneously. The use of mediastinal window setting (i.e., soft tissue) showed
      the smooth inner surface of parietal pleural fibrosis or plaque formation lying
      parallel or convex to the associated rib cage, whereas the thickened or calcified
      visceral pleura had an irregular inner surface with single or multiple
      protrusions penetrating the underlying lung substance and retraction of the
      associated pathological visceral pleural surface. We present cases of tuberculous
      calcified visceral pleura, a talc pleuritis and carcinoma abutting on the
      interlobar fissure, and clearly demonstrate the CT features.

PMID- 1995506
TI  - Modified biokinetic model for uranium from analysis of acute exposure to UF6.
AB  - Urinalysis measurements from 31 workers acutely exposed to uranium hexafluoride
      (UF6) and its hydrolysis product UO2F2 (during the 1986 Gore, Oklahoma UF6
      release accident) were used to develop a modified recycling biokinetic model for
      soluble U compounds. The model is expressed as a five-compartment exponential
      equation: yu(t) = 0.086e-2.77t + 0.0048e-0.116t + 0.00069e-0.0267t + 0.00017 e
      0.00231t + 2.5 x 10(-6) e-0.000187t, where yu(t) is the fractional daily urinary
      excretion and t is the time after intake, in days. The excretion constants of the
      five exponential compartments correspond to residence half-times of 0.25, 6, 26,
      300, and 3,700 d in the lungs, kidneys, other soft tissues, and in two bone
      volume compartments, respectively. The modified recycling model was used to
      estimate intake amounts, the resulting committed effective dose equivalent,
      maximum kidney concentrations, and dose equivalent to bone surfaces, kidneys, and
      lungs.

PMID- 1995507
TI  - Radionuclide distribution dynamics in skeletons of beagles fed 90Sr: correlation
      with injected 226Ra and 239Pu.
AB  - Data for the bone-by-bone redistribution of 90Sr in the beagle skeleton are
      reported for a period of 4000 d following a midgestation-to-540-d-exposure by
      ingestion. The partitioned clearance model (PCM) that was originally developed to
      describe bone-by-bone radionuclide redistribution of 226Ra after eight
      semimonthly injections at ages 435-535 d has been fitted to the 90Sr data. The
      parameter estimates for the PCM that describe the distribution and clearance of
      226Ra after deposition on surfaces following injection and analogous parameter
      estimates for 90Sr after uniform deposition in the skeleton as a function of Ca
      mass are given. Fractional compact bone masses per bone group (mi,COM) are also
      predicted by the model and compared to measured values; a high degree of
      correlation (r = 0.84) is found. Bone groups for which the agreement between the
      model and experimental values of mi,COM was poor had tissue-to-calcium weight
      ratios about 1.5 times those for bones that agreed well. Metabolically defined
      "surface" in PCM is initial activity fraction per Ca fraction in a given skeletal
      component for intravenously injected alkaline earth (Sae) radionuclides;
      comparisons are made to similarly defined "surface" (Sact) values from 239Pu
      injection studies. The patterns of Sae and Sact distribution throughout the
      skeleton are similar.

PMID- 1995508
TI  - Contamination and radiation exposure from 201Tl in patients undergoing dialysis
      after a nuclear medicine study.
AB  - Our institution is a major kidney research and transplant center. Hemodialysis
      patients that are scheduled for renal transplant are given a 201Tl stress test.
      Possible radiation exposure and contamination are of concern to attending
      personnel. We investigated this situation and found measurable activity in the
      effluent of patients receiving dialysis but no significant contamination of
      equipment. We determined that dialysis personnel received minimal radiation
      exposure.

PMID- 1995509
TI  - A method to automate radiological surveys: the Ultrasonic Ranging and Data
      System.
AB  - The Ultrasonic Ranging and Data System (USRADS) was developed to allow radiation
      exposure rate data and positional information to be simultaneously collected,
      stored, and analyzed in a manner more efficient than conventional survey
      techniques. USRADS is field portable using ultrasonics to locate a field surveyor
      on a site and radiofrequency to transmit data. Surveyor position (e.g.,
      measurement location within 10 cm) and an integrated instrument measurement are
      recorded and stored once each second in a microcomputer. Operational experience
      indicates that the system results in collection of greater quantity and higher
      quality of radiological data with less effort in data transcription and analysis
      and only slightly more field effort compared to conventional manual methods.

PMID- 1995510
TI  - An evaluation of the BD-100R rechargeable neutron bubble dosimeter.
AB  - The purpose of this paper is to present data gathered in the evaluation of the BD
      100R neutron bubble dosimeter done at the University of Maryland and the Naval
      Research Lab. The performance of 12 dosimeters has been followed over 15 exposure
      recharge cycles under a wide range of exposure conditions. Included in this paper
      are the results from tests on dose rate dependence, neutron energy dependence,
      beta and gamma exposure, and recharge cycle performance. A statistical analysis
      of the reusability performance of the dosimeter as a function of dose equivalent
      is also presented.

PMID- 1995511
TI  - Theoretical response of a ZnS(Ag) scintillation detector to alpha-emitting
      sources and suggested applications.
AB  - The classic problem of alpha absorption is discussed in terms of the quantitative
      determination of the activity of "weightless" alpha sources and the specific
      alpha activity of extended sources accounting for absorption in the source medium
      and the window of a large area ZnS(Ag) scintillation detector. The relationship
      for the expected counting rate gamma of a monoenergetic source of active area A,
      specific alpha activity C, and thickness H that exceeds the effective mass
      density range Rs of the alpha particle in the source medium can be expressed by a
      quadratic equation in the window thickness x when this source is placed in direct
      contact with the window of the ZnS(Ag) detector. This expression also gives the
      expected counting rate of a finite detector of sensitive area A exposed to an
      infinite homogeneous source medium. Counting rates y obtained for a source
      separated from a ZnS(Ag) detector by different thicknesses x of window material
      can be used to estimate parameter values in the quadratic equation, y = a + bx +
      cx2. The experimental value determined for the coefficient b provides a direct
      estimation of the specific activity C. This coefficient, which depends on the
      ratio of the ranges in the source medium and detector window and not the ranges
      themselves, is essentially independent of the energy of the alpha particle.
      Although certain experimental precautions must be taken, this method for
      estimating the specific activity C is essentially an absolute method that does
      not require the use of standards, special calibrations, or complicated
      radiochemical procedures. Applications include the quantitative determination of
      Rn and progeny in air, water, and charcoal, and the measurement of the alpha
      activity in soil and on air filter samples.

PMID- 1995512
TI  - Abandoned Rayrock uranium mill tailings in the Northwest Territories:
      environmental conditions and radiological impact.
AB  - Field and laboratory investigations were undertaken of the environment
      surrounding abandoned U mill tailings at Rayrock, Northwest Territories, Canada,
      to examine the extent of 226Ra and U contamination. Samples of ground water,
      surface water, and unconsolidated geological material from the Rayrock area were
      collected for chemical and radiochemical analyses. Results indicated that the
      surface waters contained levels of 226Ra as high as 20 Bq L-1, 210Pb as high as
      1.1 Bq L-1, and ground water U as high as 2800 micrograms L-1. Lower levels of
      226Ra, 210Pb, and U, 3.6 Bq L-1, 0.5 Bq L-1, and 4 micrograms L-1, respectively,
      were found in a small lake adjacent to the tailings area. Analysis of tailings
      and soil in the immediate vicinity indicates that the radionuclides and U are
      mobilized and can move within the tailings. Some of the mobilized radionuclides
      will be bound by the surrounding peat. The remainder may move to Lake Alpha in
      ground water. Surface water flow also transports some contaminants both in the
      water of Alpha Creek and by washing tailings into Lake Alpha. The potential
      annual external and internal dose equivalents to a hypothetical resident were
      calculated based on exposure from the abandoned U mill tailings, drinking water,
      and fish caught in the lakes in the vicinity of the tailings. While Alpha Creek
      and Lake Alpha water showed evidence of contamination, the rest of the water
      system and the fish were at natural background levels of radioactivity.

PMID- 1995513
TI  - Calculation of effective dose-equivalent responses for external exposure from
      residual photon emitters in soil.
AB  - Effective dose-equivalent responses have been calculated for external exposure
      from residual photon emitters in soil. The calculations are based on the
      assumption that the receptor is located 1 m above the contaminated ground. A
      Monte Carlo algorithm was developed to perform the photon transport calculation
      for the soil/air configuration, in which the soil constituents were assumed to be
      similar to those of the earth's crust. Photon cross-sections for soil were based
      on the latest cross-sectional information generated by the U.S. National
      Institute of Standards and Technology. For every incident photon at the receptor,
      an estimate of the air-absorbed dose was calculated first and then converted into
      the effective dose equivalent. The effective dose equivalent is based on the
      concept of weighted organ doses, as recommended by the ICRP. The ICRP's latest
      conversion coefficients were used to transform point air-absorbed doses into
      effective dose equivalents. Baseline effective dose responses were obtained for
      monoenergetic photon sources assumed to be distributed uniformly in soil for
      energies ranging from 0.01 to 10 MeV, soil thicknesses from 0 to 5 mean-free-path
      (mfp) lengths, and soil densities from 1 to 2 g cm-3. On the basis of the
      calculated dose responses, empirical relationships were obtained for correlating
      the dose responses with the soil depths and densities for each source energy. The
      derived correlations contain a convenient exponential form that describes the
      depth-dose relationship for an estimated accuracy within about 15%; soil
      densities show an inverse relationship with dose responses. Results of the
      effective dose-equivalent response can be used to calculate effective dose
      equivalent responses for gamma-emitting radionuclides that are commonly
      identified as residual radioactive materials in soil.

PMID- 1995516
TI  - Significance of neutrons from the atomic bomb at Hiroshima for revised radiation
      risk estimates.

PMID- 1995514
TI  - Chernobyl fallout in southern and central Finland.
AB  - To study the levels and distributions of radionuclides released in the Chernobyl
      accident, we sampled surface peat from 62 sites in Southern and Central Finland
      and measured 131I, 134Cs, 137Cs, 132Te, 140Ba, 103Ru, 90Sr, 141Ce, and 95Zr. The
      distribution of fallout activities was highly uneven, depending on movement of
      the contaminated air mass and rainfall distribution during the critical days. The
      highest values observed were 420 kBq m-2 of 131I and 70 kBq m-2 of 137Cs. The
      nuclide ratios showed wide and partly unexpected variations. The high-boiling
      point, or nonvolatile, elements Ce and Zr were spread mostly on a 200-km-wide
      zone extending across Finland from southwest to northeast. The more volatile
      elements, I, Ce, and Te, showed quite a different, more widespread, fallout
      distribution, while an intermediate behavior was observed for Ba, Ru, and
      possibly Sr. These results can be explained by assuming that pulverized nuclear
      fuel material released in the reactor explosion on 26 April reached Finland via
      Poland and the Baltic Sea and traversed the country along the above-mentioned
      narrow zone, while volatile material, evaporated in the reactor fire from 26
      April to 5 May, arrived in several waves and was consequently more widely and
      evenly spread. From their elemental melting and boiling points, Ru and Mo would
      appear to belong to the nonvolatile group and Sr to the volatile. Yet, their
      actual behaviors were opposite; Ru in particular was found in the nonvolatile as
      well as the volatile fallout, possibly because Ru activities were present in the
      fuel partly in the metallic state and partly as volatile oxides.

PMID- 1995517
TI  - Radon grab sampling using an aerosol can.

PMID- 1995515
TI  - Distribution of radium-induced bone cancers in beagles and comparison with
      humans.

PMID- 1995519
TI  - Data base management system for a radiation safety program.
AB  - A data base management system (DBMS) has been developed that simplifies the
      retrieval of data concerning radioisotope use at a university and hospital. The
      system customizes software that is commercially available to perform several
      functions. Reports can be developed concerning receipt of radioactive materials,
      radioactive waste disposal, and research proposals submitted by investigators.
      Reports can be prepared that utilize the software's ability to perform numerical
      calculations. The main advantage of the DBMS is that it allows the easy retrieval
      of information that is used in the day-to-day operation of a radiation safety
      office; it also provides easy access and manipulation of data for the preparation
      of reports, budget proposals, and justifications for purchases.

PMID- 1995520
TI  - A commentary on an association of malignant melanoma with nonultraviolet
      radiation exposure.

PMID- 1995518
TI  - Assessment of the indoor Rn contribution of Swiss building materials.

PMID- 1995521
TI  - Phosphorus-32 skin decontamination.

PMID- 1995522
TI  - Long-term follow-up of Ewing's sarcoma of bone treated with combined modality
      therapy.
AB  - Between 1968 and 1980, 107 consecutive patients with Ewing's sarcoma of bone were
      entered on three sequential combined modality treatment protocols (S2, S3, S4) at
      the National Cancer Institute (NCI). Protocol treatment involved 4 cycles of two
      drug [cyclophosphamide (CTX) and vincristine (VCR)] or three drug [CTX and VCR
      with either actinomycin-D (ACT-D) or doxorubicin (ADR)] regimens and local
      irradiation (50 Gy) to the involved bone. Eighty patients presented with
      localized disease and 27 patients had metastatic disease at presentation,
      including 11 patients with multiple metastatic sites. With a median potential
      follow-up of greater than 15 yrs (range 8-20 yrs), 28 pts (27%) remain alive.
      Disease-free (DFS) and overall survival (OS) decreased most rapidly during the
      initial 5 yrs of follow-up with 5-yr DFS of 29% and 5-yr OS of 39%. Only two
      patients with metastases at presentation are long term (greater than 5 yr)
      survivors. For localized disease patients, the 2, 5, 10, and 15 yr DFS and OS are
      52%, 37%, 35%, and 33% DFS and 68%, 51%, 39%, and 34% OS, respectively. Eleven
      patients relapsed locally as the first site of failure. Using the Cox
      proportional hazards model, four significant variables for both DFS and OS were
      recognized, including metastatic disease at presentation, age greater than 25
      yrs, high LDH in localized disease patients, and central primary tumor in
      localized disease patients in decreasing order of significance. We conclude that
      a majority of these patients with Ewing's sarcoma of bone relapsed within 5 yrs
      of presentation although late relapse (5-15 yrs) did occur. Local failure
      occurred in 20% of patients using these combined modality treatments but had no
      impact on overall survival.

PMID- 1995525
TI  - Curative radiotherapy following chemotherapy for invasive bladder carcinoma (a
      preliminary report).
AB  - Twenty-five patients with invasive transitional cell carcinoma of the bladder
      (Stage T2, T3, T4) received combined modality therapy using four cycles of
      methotrexate, vinblastine, adriamycin, and cisplatin (MVAC) chemotherapy followed
      by surgery or radiation therapy (RT). Sixteen patients had complete (N = 8) or
      partial (N = 8) response to MVAC. Curative RT was delivered to 11 responders with
      T2 or T3 disease and to 2 patients with T4 disease. All 11 with T2 and T3 disease
      are currently alive, 7 with normal bladder function. The two with T4 disease are
      dead of disease. Three patients required salvage cystectomy for local recurrence
      and one patient had cystectomy for bladder stones. Follow-up ranged from 11 to 50
      months with a median of 31 months. No late chemo-radiotherapy treatment-related
      complications to the intestines or in bladder function (other than one bladder
      stone formation) occurred. These preliminary results are encouraging and warrant
      further evaluation of this innovative approach in treating invasive carcinoma of
      the bladder. T2 and T3 patients with a complete or partial response to MVAC may
      be excellent candidates for a bladder-sparing treatment.

PMID- 1995524
TI  - Twenty years experience of interstitial iridium brachytherapy in the management
      of soft tissue sarcomas.
AB  - From February 1968 to February 1988, 50 patients above 10 years of age with a
      soft tissue sarcoma were treated with interstitial brachytherapy, combined with a
      wide excision. After pathologic review, 48 were included in the final analysis. A
      pathological grading was made possible in 41, which showed a majority of high
      grades (2 + 3 = 86%). Patients presented mainly with small (less than 5 cm: 36)
      or mid-size lesions (greater than 5 cm: 12). The tumor was located in the limbs
      (32), trunk (9), and head and neck (7). Four patients had metastases at the time
      of treatment. Brachytherapy was part of the initial treatment in 22 cases, and of
      a salvage procedure after previous excision(s) combined or not with another form
      of treatment in 26. A uniform technique of iridium 192 wires after-loaded in
      plastic tubing was used. Sixty Gy median doses were delivered with brachytherapy
      alone (44) or combined with external beam (4). Sixteen patients also received an
      adjuvant chemotherapy. Follow up ranged from 16 months to 20 years (median 82
      months). At the time of analysis, two patients (4%) only had failed in the
      irradiated volume, but the marginal failures rate (14:31%) was unexpectedly high.
      Seven of the patients who failed (43%) were salvaged by a second similar
      procedure. The 5-year survival was 62% in non-previously treated patients and
      56.5% in previously treated ones (pNS). By multivariate analysis, only the tumor
      location appeared predictive of LF (p less than 0.01), which in turn was strongly
      correlated with the metastatic outcome (p less than 0.01). Necroses were observed
      in 17 cases (35%) and associated with a benign course in most of them. High dose
      brachytherapy combined with conservative surgery is highly effective in small and
      mid-size soft tissue sarcomas located in the extremities and head and neck,
      whereas in trunk and in recurrent tumors, the adjunction of large fields external
      radiotherapy and/or possibly polychemotherapy appears necessary.

PMID- 1995526
TI  - Intentions and outcomes in the radiotherapeutic management of epidemic Kaposi's
      sarcoma.
AB  - The indications for and outcome of radiotherapy for 226 epidemic Kaposi's
      sarcomas are reported. The overall likelihood of obtaining complete regression of
      tumor masses was 68%, although residual purple pigmentation remained in 20%.
      Local recurrence developed in 9%. The indications for treatment were not equally
      represented. Palliation of pain or improvement of the patient's appearance were
      the most common indications for treatment. Kaposi's sarcoma lesions do not all
      behave in a like manner. Best fit log-linear models of associations among the
      variables were derived. They demonstrated that the combination of treatment
      intention, anatomic site, and Karnofsky score predicted the short-term and long
      term tumor response. The intention of treatment was closely linked to the
      anatomic site of treatment and in concert directly influenced outcome. The host's
      Karnofsky score was an independent predictive factor, but had less impact on
      outcome than did site or intention. Our data demonstrate that case selection can
      markedly alter the observed response rate of epidemic Kaposi's sarcoma to
      radiotherapy. This finding should be considered in future analyses of trials that
      test the efficacy of treatment for this disease.

PMID- 1995523
TI  - Influence of the fractionation of total body irradiation on complications and
      relapse rate for chronic myelogenous leukemia. The Groupe d'Etude des greffes de
      moelle osseuse (GEGMO).
AB  - One hundred eighty patients with chronic myelogenous leukemia, who received an
      unmanipulated marrow graft from an Human Leucocyte Antigen identical sibling
      donor, were reported to our group (G.E.G.M.O.) by 21 transplant teams. All were
      grafted after a total body irradiation-cytoxan conditioning regimen. Of these 180
      patients, 126 were non-randomly assigned to single dose total body irradiation
      (STBI group) and, 54 to fractionated total body irradiation (FTBI group). With a
      median follow-up of 40 months, there is no statistically significant difference
      in the 5-year survival rate between the two groups (51% for the whole
      population). In a first step we demonstrate by multivariate analysis that total
      body irradiation fractionation can dramatically decrease the incidence of
      interstitial pneumonitis. However, a multivariate analysis of potent risk factors
      for relapse post-transplant strongly suggests that TBI fractionation is also
      linked to an increased relapse rate. So, a sparing effect of fractionation for
      lung tissue could be offset by a less effective leukemic stem cell kill. Those
      results from a retrospective, non-randomized, multi-institutional study clearly
      need additional clinical data, ideally from a randomized study.

PMID- 1995527
TI  - Fraction size in external beam radiation therapy in the treatment of melanoma.
AB  - RTOG 83-05 was a prospective randomized trial evaluating the effectiveness of
      high dose per fraction irradiation in the treatment of melanoma. Retrospective
      analysis suggested a dose response curve of melanoma to external beam irradiation
      as the dose per fraction is increased. RTOG 83-05 randomized patients with
      measureable lesions to 4 x 8.0 Gy in 21 days once weekly to 20 x 2.5 Gy in 26-28
      days, 5 days a week. One hundred thirty-seven patients were randomized and 126
      patients were evaluable: 62 patients in the 4 x 8.0 Gy arm and 64 patients in 200
      x 2.5 Gy arm. Patient characteristics were essentially identical. Stratification
      was performed on lesions less than 5 cm or greater than or equal to 5 cm. The
      study was closed on May 31, 1988 when interim statistical analysis suggested that
      further accrual would not reveal a difference between arms. Response rate overall
      was complete remission 23.8%, partial remission 34.9%. The 4 x 8.0 Gy arm
      exhibited a complete remission of 24.2% and partial remission of 35.5%. The 20 x
      2.5 Gy arm exhibited a complete remission of 23.4% and partial remission of
      34.4%. There was no difference between arms.

PMID- 1995528
TI  - Deterioration in lung function following hemithorax irradiation for pleural
      mesothelioma.
AB  - Thirty-four patients receiving high-dose hemithorax irradiation as part of the
      treatment for pleural mesothelioma were studied with regard to changes in lung
      function following irradiation, and these changes were correlated with the
      radiologically-assessed lung injury. The latter was scored from 0 to 500 and
      found to be severe by 6 months (mean score 360), very severe by 9 months (mean
      score 430), and nearly total by 12 months (mean score 480) after treatment.
      Forced vital capacity and diffusing capacity both showed a significant decline at
      1.5-2 months following the end of radiotherapy and thereafter up to the end of
      the 1 year follow-up period. Neither of these variables could be correlated
      consistently with the radiologically-assessed changes. Hypoxemia and pathological
      physiological shunting increased transiently 1-2 months after irradiation in 2 of
      the 6 patients monitored. The observed radiologically-assessed final effects of
      high-dose hemithorax irradiation are compatible with a total loss of lung
      function on the irradiated side. Before this form of treatment is used, lung
      function should be evaluated as for pneumonectomy.

PMID- 1995529
TI  - Definitive radiation therapy for localized prostatic adenocarcinoma.
AB  - From 1974 to 1987, a total of 199 patients with prostatic carcinoma localized to
      the pelvis were treated with definitive external beam radiation therapy at the
      Istituto Medico e di Ricerca Scientifica. The median follow-up for all 126
      surviving patients was 60 months. Actuarial 5-(and 10-) year overall survival
      rates for U.I.C.C. clinical Stage T1-2, T3 and T4 disease were 76.1% (58.5), 66%
      (42.5), and 27.6%, respectively. The corresponding 5- and 10-) year disease
      specific survival rates were 81.7% (73), 72.5% (57.4), and 36.2%. The
      corresponding values of disease-free survival were 81.3% (76.8), 59.2% (57), and
      17%, respectively. In 120 patients with more than 5 years of follow-up, local
      failure was seen alone in eight patients (6.6%) and associated with distant
      metastases in 19 patients (15.8%). In 28 patient (23.3%), distant metastases were
      observed alone. The median survival from the first evidence of metastases was 20
      months, with no patient surviving beyond 5 years. The incidence of complications
      was acceptable. Serious complications, consisting of stenosis of both ureters and
      sigmoid colon requiring both urinary and intestinal diversion, occurred in two
      patients (1.3%). This study reveals that external radiotherapy is an efficacious
      and safe modality for locoregional control of prostate cancer.

PMID- 1995530
TI  - Interleukin 1 alpha stimulates hemopoiesis but not tumor cell proliferation and
      protects mice from lethal total body irradiation.
AB  - Interleukin 1 alpha (IL-1) is a polypeptide/glycoprotein growth factor with
      multiple functions including the modulation of hematopoietic cell proliferation
      and differentiation. In vivo studies were performed with C57BL/6J mice injected
      with 0, 0.2, or 2.0 micrograms of IL-1 24 hr before or after lethal total body
      irradiation (TBI) (9.5 Gy). More mice in the groups administered IL-1 before TBI
      survived (90% of the 2.0 micrograms group) than those treated 2 or 24 hr after
      TBI, which was still slightly superior to the uninjected group, which all died
      within 15 days (p = .0001). Proliferation of bone marrow granulocyte/macrophage
      colonies following split dose TBI was also greatest for mouse groups treated with
      IL-1 prior to TBI. These experiments support data from other investigators that
      IL-1 stimulation of BM is related to IL-1 timing with respect to TBI. Stimulation
      of hemopoiesis was also assessed in terms of changes in peripheral blood and BM
      cell numbers and cell cycle kinetics using an electronic particle counter and
      flow cytometric techniques. Mice injected with 2 micrograms of IL-1 showed an
      initial decline (at 3-6 hr) and then a selective proliferation (24-48 hr) of
      early and more committed progenitor cells to 125% and 200% of control values,
      respectively. Peripheral blood counts rose accordingly. Cells in S and G2/M
      phases increased over 10 hr and then declined in number. It thus appeared that
      some synchronization of cell cycling occurred, which might place cells in a more
      radioresistant phase of the cell cycle. The glutathione (GSH) content and
      synthesis in BM cells were measured by isocratic paired-ion high performance
      liquid chromatography and 35S-labelled cysteine incorporation into the GSH
      tripeptide. An increase in cellular GSH content and synthesis was demonstrated
      following IL-1 which lasted 24 hr, suggesting a possible mechanism for the
      radioprotection by IL-1. To determine the potential for achieving a favorable
      therapeutic ratio, KHT tumor-bearing mice were injected with 2.0 micrograms IL-1.
      No change in tumor diameters or weights or tumor cell clonogenicity between IL-1
      treated or untreated animals was observed. These experiments strongly support a
      role for IL-1 in stimulating bone marrow to overcome the myelosuppressive effects
      of irradiation.

PMID- 1995531
TI  - Tumor hypoxia can be exploited to preferentially sensitize tumors to fractionated
      irradiation.
AB  - The present study describes a new way in which tumors may be made more sensitive
      to fractionated irradiation without affecting the sensitivity of surrounding
      normal tissues. It involves exploiting the cycling or intermittent hypoxia that
      occurs in at least some solid tumors, but not in normal tissues, using a new drug
      SR 4233, a benzotriazine di-N-oxide, which is rapidly metabolized in hypoxic
      cells to a product that kills these cells. Using this approach with a rodent
      tumor in a fractionated x-ray treatment regimen similar to that used in human
      radiotherapy, the addition of SR 4233 produced a large enhancement of the
      radiation response of the tumor with no change in the sensitivity of normal mouse
      skin. Under identical circumstances, there was no effect of the hypoxic cell
      radiosensitizer SR 2508, showing that SR 4233 with intermittent hypoxia was
      superior to a protocol which sensitized the hypoxic cells to doses of 2.5 Gy per
      fraction.

PMID- 1995532
TI  - Muscle injury following experimental intraoperative irradiation.
AB  - The paraaortic region of beagle dogs was irradiated to 15 to 55 Gy intraoperative
      irradiation, 10 to 47.5 Gy intraoperative irradiation following 50 Gy external
      beam irradiation in 25 fractions, or 50 to 80 Gy external beam irradiation in 30
      fractions. Six MeV electrons were used for intraoperative irradiation, and
      external beam irradiation was done using photons from a 6 MV linear accelerator.
      The psoas muscle in the irradiation field was examined histomorphometrically 2 or
      5 years after irradiation. The percentage of muscle fibers and capillaries
      decreased, whereas the percentage of connective tissue increased with increased
      dose for both intraoperative irradiation only and intraoperative irradiation plus
      external beam irradiation. The dose causing a 50% decrease in the percentage of
      muscle fibers was 21.2 Gy and 33.8 Gy at 2 and 5 years, respectively, after
      intraoperative irradiation alone, and 22.9 Gy and 25.2 Gy at 2 and 5 years,
      respectively, after intraoperative irradiation combined with 50 Gy external beam
      irradiation. The ED50 for severe vessel lesions was 19.2 Gy and 25.8 Gy at 2 and
      5 years, respectively, after intraoperative irradiation alone and 16.0 Gy and
      18.0 Gy at 2 and 5 years, respectively, after intraoperative irradiation combined
      with 50 Gy external beam irradiation. External beam irradiation alone caused a
      slight decrease in percentage of muscle fibers with increased dose, and vessel
      lesions were infrequent or mild. Radiation-induced muscle injury was
      characterized by loss of muscle fibers, decreased fiber size, severe vessel
      lesions, hemorrhage, inflammation, coagulation necrosis, and fibrosis. These
      histopathologic characteristics distinguish this muscle injury from that caused
      by neurogenic atrophy. These data indicate that radiation-induced muscle injury
      most likely was caused by injury of the supporting vasculature. The lesions
      produced were largely a function of the single intraoperative dose rather than
      the external beam fractionated doses. Furthermore, it appears that 20 to 25 Gy
      intraoperative irradiation combined with 50 Gy external beam irradiation may be
      near the maximum tolerated dose by sublumbar musculature and its supporting
      vasculature.

PMID- 1995533
TI  - Reoxygenation in a rat rhabdomyosarcoma tumor following X-irradiation.
AB  - The paired survival curve technique was used to characterize the rate at which
      the fraction of hypoxic cells in rat rhabdomyosarcoma R-1 tumors returns to the
      preirradiation value of 37% following a single dose of 225-kVp X rays. Tumors
      were administered a conditioning x-ray dose of 15-Gy, followed at 0, 3, 6, 12,
      24, or 48 hr by a 5-Gy, 10-Gy, or 15-Gy dose of X rays under air-breathing
      conditions or under hypoxic conditions produced by nitrogen-gas asphyxiation 5
      min prior to irradiation. Cellular surviving fractions were determined by the
      tumor excision assay following in vivo irradiation. From the ratio of the
      survival fractions measured for tumor cells from air-breathing and hypoxic
      animals, the fraction of hypoxic cells was determined as a function of time
      postirradiation. These results indicated that immediately following a 15-Gy dose
      of X rays, essentially 100% of the viable cells remaining were hypoxic. The
      tumors reoxygenated rapidly, returning to the preirradiation level of 37% during
      the first 6 hr postirradiation.

PMID- 1995534
TI  - The role of radiation therapy in the treatment of locally unresectable or
      metastatic carcinoid tumors.
AB  - Forty-four patients irradiated for metastatic or unresectable carcinoid tumors at
      Memorial Sloan-Kettering Cancer Center from 1950 to 1986 were studied. The
      response to radiation was analyzed at four sites: epidural space (11 pts), brain
      (8 pts), bone (8 pts), and abdominal (17 pts). Although survival was generally
      poor, substantial palliation was achieved in most cases. No patient with brain
      metastases had progression of intracranial disease after radiation therapy
      (median dose: 3300 cGy); all died of progression of systemic metastases (median
      survival: 4 months). Infield control following radiation therapy for epidural and
      osseous metastases was achieved in 77% and 78% of sites, respectively, with
      median doses of 3000 cGy and 4000 cGy. Median survival for epidural and bone
      metastases was 11 and 13 months, respectively. In-field control was obtained in
      62% of patients with intraabdominal disease (median dose: 2700 cGy). Among the
      subset of seven patients who were irradiated at ten sites of unresectable
      abdominal (non-hepatic) disease, the median survival was 23 months with 80%
      achieving a complete or partial response and 50% maintaining permanent in-field
      control. No dose-response relationship was demonstrated. Radiation therapy can
      achieve local control and symptomatic palliation in most patients with metastatic
      carcinoid tumors. Our current recommendation would be to treat non-hepatic sites
      with 4500-5000 cGy in 4-5 weeks. More rapid fractionation schemes could be used
      for patients with limited life expectancies.

PMID- 1995535
TI  - The response of the KHT sarcoma to radiotherapy as measured by water proton NMR
      relaxation times: relationships with tumor volume and water content.
AB  - The potential application of magnetic resonance imaging (MRI) to predict tumor
      response to radiotherapy is investigated. The water proton spin-lattice and spin
      spin relaxation times (T2 and T2, respectively) of murine sarcomas (designated
      KHT) were measured shortly after excision. This study has demonstrated
      significantly different responses in T1 and T2 between the control and the
      irradiated tumors at various times following single doses of X rays. Quite
      generally, the changes in relaxation times correlated with the changes in tumor
      water content, indicating that the MR relaxation-time probes are fairly sensitive
      to radiation-induced edema and dehydration. The possible relationships between
      the T1 and T2 responses and radiobiological effects such as those on tumor blood
      flow, vascular permeability, physiological state of cells, and cell death are
      discussed. It is conceivable that the findings obtained from this investigation
      could be extended to in situ studies for potential applications in clinical
      radiotherapy.

PMID- 1995536
TI  - The effect of lonidamine (LND) on radiation and thermal responses of human and
      rodent cell lines.
AB  - Rodent and human cells were tested for response to Lonidamine (LND) (1-(2,4
      dichlorobenzyl) 1-indazol-3-carboxylic acid) combined with radiation or
      hyperthermia. Lonidamine exposure before, during, and after irradiation caused
      varying degrees of inhibition of potentially lethal damage (PLD) repair which was
      cell line dependent. In human glioma, melanoma, squamous cell carcinoma, and
      fibroblasts, LND exposure did not inhibit or only partially inhibited repair of
      potentially lethal damage. LND up to 100 micrograms/ml produced only a low level
      of toxicity in these cells and only slightly inhibited glucose consumption at the
      maximum concentration. In human glioma cells, LND treatment alone did not inhibit
      PLD repair, but when combined with hyperthermia treatment at moderate levels
      easily achievable in the clinic, there was complete inhibition of potentially
      lethal damage repair. These data suggest that LND effectiveness is cell type
      dependent. Combinations of LND, hyperthermia, and radiation may be effective in
      cancer therapy especially in tumors such as glioma in which repair of potentially
      lethal damage may be extensive.

PMID- 1995537
TI  - Stereotactic target point verification of an X ray and CT localizer.
AB  - Stereotactic radiosurgery with a linear accelerator requires the accurate
      determination of a target volume and an accurate match of the therapeutic
      radiation dose distribution to the target volume. X ray and CT localizers have
      been described that are used to define the target volume or target point from
      angiographic or CT data. To verify the accuracy of these localizers, measurements
      were made with a target point simulator and an anthropomorphic head phantom. The
      accuracy of determining a known, high contrast, target point with these
      localizers was found to be a maximum of +/- 0.5 mm and +/- 1.0 mm for the X ray
      and CT localizer, respectively. A technique using portal X rays taken with a
      linear accelerator to verify the target point is also described.

PMID- 1995538
TI  - Whole body hyperthermia: a potent radioprotector in vivo.
AB  - Interleukin-1 has been reported to be an effective radioprotective agent in mice
      subjected to lethal doses of irradiation. Production of Interleukin-1 can be
      increased by whole body hyperthermia. Therefore, whole body hyperthermia was
      assessed for its efficacy in protecting the lethal effects of ionizing radiation
      in DBA/2 mice. One hour of 40 degrees C +/- 0.2 whole body hyperthermia given 20
      hr before 900 cGy total body irradiation protected 100% of DBA/2 mice from an LD
      100/16 radiation dose (dose of irradiation that killed 100% of the mice in 16
      days). Lethal doses of total body irradiation produced profound monocytopenia,
      decreased cellularity of thymus, spleen, and bone marrow, and suppressed
      Interleukin-1 production. Interleukin-1 production was determined using the
      thymocyte proliferation assay. Whole body hyperthermia accelerated recovery of
      blood leukocytes by up to 5 days post-total body irradiation in DBA/2 mice.
      Thymocytes, spleen, and bone marrow cells were activated by whole body
      hyperthermia, as assessed by the cell's response to Concanavalin A. This was
      accompanied by accelerated Interleukin-1 generation. Our results provide the
      first evidence that whole body hyperthermia acts as a potent radioprotector in
      vivo, effects that may be mediated by Interleukin-1.

PMID- 1995539
TI  - Characteristics of improved microwave interstitial antennas for local
      hyperthermia.
AB  - The heating potentials of two newly-developed microwave interstitial antennas are
      reported in this paper. The longitudinal (parallel to the antenna) and transverse
      (over a plane perpendicular to the antenna) specific absorption rate (SAR)
      distributions of single and an array of four parallel antennas were measured in a
      muscle equivalent phantom and their performance characterized at 915 MHz in terms
      of the following parameters: peak depth (location of the profile peak with
      respect to the surface), 50% HL (effective heating length over which SAR greater
      than 50% of the peak normalized SAR), dead length (axial length at the antenna
      tip with SAR less than 50% of peak normalized SAR), and the variations of the
      specific absorption rate pattern relative to the depth of insertion. The results
      are analyzed and discussed in terms of these parameters and other factors
      important in the clinical use of these antennas for effective interstitial
      hyperthermia.

PMID- 1995540
TI  - Secondary external-beam radiotherapy and hyperthermia for local recurrence after
      125-iodine implantation in adenocarcinoma of the prostate.
AB  - At Stanford, six patients underwent a course of external radiotherapy after local
      recurrence following 125-iodine implantation. Four of the six patients also
      received concomitant hyperthermia. Four patients were initially managed with
      hormonal manipulation at time of local relapse and subsequently received external
      beam radiotherapy with or without hyperthermia. The hyperthermia was non
      invasively induced using an annular phased array radiative electromagnetic
      system. Treatment was well tolerated, and none of the patients experienced severe
      rectal or bladder complications. Three patients are free from disease; one
      patient experience local-regional recurrence based on biopsy; one recurred in the
      bladder, was treated with cystoprostatectomy and subsequently succumbed to
      metastatic disease; and one patient died of presumed metastatic disease. External
      beam irradiation with concurrent hyperthermia can be safely delivered to treat
      locally recurrent prostatic carcinoma after 125-iodine implantation.

PMID- 1995541
TI  - Professional liability in radiotherapy: experience of the Fletcher Society.
AB  - We have conducted a study to ascertain the pattern and background of lawsuits
      related to the practice of radiotherapy among physician-members of the Gilbert H.
      Fletcher Society. Eighty-four percent of the members of the society replied to
      the questionnaire; one-third have sustained a lawsuit with an actuarial
      probability of 30% at 10 years, 50% at 20 years, and 65% at 30 years. Lawsuits
      occurred across the spectrum of practice type, location, experience, disease
      site, and technique. Two-thirds of the suits were dropped or successfully
      defended. Regardless of the outcome, the experience of being sued was found to
      have influenced 33% of those sued to practice more conservatively.
      Recommendations of the membership directed towards minimizing the risk of being
      sued, while maintaining an aggressive treatment philosophy, are presented. Based
      on this study, we believe that formal medicolegal education should be included in
      the curriculum of radiotherapy residents' training program.

PMID- 1995542
TI  - Biodistribution, with high uptake by the reproductive tract, of an
      intraperitoneally infused radiohalogenated steroidal estrogen-receptor ligand.
AB  - We infused [123I]16 alpha-(123I)-iodo-estradiol ([123I]E2) intraperitoneally
      (i.p.) into swine to study its biodistribution and to explore the i.p. use of
      radiohalogenated steroid estrogen-receptor (ER) ligands as a potential option for
      diagnosing and treating intra-abdominal, retroperitoneal, and distant sites of
      advanced ER-rich malignancies. Fifty to 80% of the radiolabel was absorbed from
      the peritoneal cavity within 30 minutes, and 30 to 50% of the infused radiolabel
      was excreted in the urine within 2 hr. The rate of biliary clearance was maximal
      within 25 minutes. At 3 hr, the ER-rich reproductive tract had greater than 63
      times the concentration of radiolabel in blood; the former was blocked by non
      labeled competitors for ER. Uptake by non-ER-rich tissues, compared to blood,
      ranged from 0.7:1 (heart and lungs) to 16:1 (spleen); the omentum, however,
      exhibited a concentration as high as 64:1, which was not blocked by non-labeled
      ER ligands. Uptake by ER-rich target tissue remained high when charcoal was used
      to prevent reabsorption of radiolabel from the digestive tract after its biliary
      excretion, and when the products of biliary excretion were removed by
      catheterization of the common bile duct. Neither charcoal nor exteriorization of
      bile appeared to affect urinary clearance of the radiolabel over the time course
      of the experiments. Taken together with the recent development of syntheses that
      yield radiohalogenated sex steroid receptor ligands of high specific activity,
      our findings are encouraging for the potential application of radiolabeled
      ligands as i.p. administered pharmaceuticals. The advantage of the i.p. route is
      that it provides direct uptake of the pharmaceutical by free-floating clusters
      and individual cancer cells in ascitic fluid, as well as delivery via the
      circulation to vascularized intra- and/or extraperitoneal metastases.

PMID- 1995543
TI  - Cancer of the anal canal: report on the experience of 61 patients.
AB  - We report our experience on 61 anal canal epidermoid carcinoma bearing patients.
      The patients are divided into three therapeutic groups: a) 14 patients treated
      with combined surgery and preoperative radiotherapy (37.8 Gy in 18 fractions and
      21 days); b) 28 patients treated with 60Co and electrontherapy (total tumor dose
      of 60 to 65 Gy); c) 19 patients treated with external cobaltherapy (30 Gy/10
      fractions/12 or 15 days) followed 1 to 2 months later by interstitial
      brachytherapy with Iridium 192 (20 Gy). Local control was observed in 41 out of
      61 patients (67.2%). Out of the six patients who underwent salvage abdomino
      perineal resection, five were locally cured at 5 years. The overall 5-year
      survival is 78.6%; the corrected 5-year survival is 88.8%. Analysis of prognosis
      factors shows a direct relation between local control survival and the loco
      regional extension. The 5-year survival was 90.9% in the first therapeutic group,
      90.9% in the second group, and 94.7% in the third group. The 5-year survival
      rates according to the stage and to treatment were as follows: Stage T1 N0 100%
      in the 1st therapeutic group, 85.7% in the 2nd group, 100% in the 3rd group; for
      Stage T2 N0 80% in the 1st group, 90.9% in the 2nd group, 90% in the 3rd group;
      for Stage T3 N0 83.3% in the 1st group, 85.7% in the 2nd group, and 66.6% in the
      3rd group. The rates of sphincter preservation were 85.7% in the 2nd group and
      94.7% in the 3rd group. These results show the incidence of loco-regional
      extension on the prognosis and the usefulness of conservative treatments.

PMID- 1995544
TI  - The morbidity of salvage surgery following conventional radiotherapy and
      continuous, hyperfractionated accelerated radiotherapy (CHART).
AB  - A comparison was made of the morbidity of surgery for loco-regional recurrence in
      patients with advanced cancer of the head and neck region following continuous
      hyperfractionated accelerated radiotherapy (CHART), after conventional
      radiotherapy, and also in a group following surgery only as the primary
      treatment. Post-surgical morbidity occurred in 14 (77%) of the 18 patients
      treated with CHART, of whom 11 (78%) required a further surgical procedure. In
      the conventional group, morbidity occurred in 14 (58%) of the 24 patients, of
      whom 9 (64%) required further surgery. Finally, in the surgical group morbidity
      occurred in 13 (48%) of the 27 patients, of whom 7 (54%) required further
      surgery. Because of the many factors that may influence the chance of morbidity
      and of the small number of cases, considered statistical analysis is not
      meaningful and there must be caution in the interpretation of results. When
      allowance is made for the greater frequency of more advanced tumors and for sites
      in the oropharynx and oral cavity, where procedures associated with greater risk
      of complication were performed, the morbidity seen after surgery was performed
      upon CHART patients appeared to be no greater than when conventional radiotherapy
      had been given. As expected, the surgery only group showed less morbidity than
      either of the radiotherapy groups.

PMID- 1995545
TI  - Local recurrence of soft tissue sarcoma following brachytherapy.
AB  - Twenty-five patients with soft tissue sarcomas were treated with Ir192 implants
      following wide local excision at our institution between 1982 and 1987. External
      beam radiotherapy was given in addition to the implant in a majority of patients.
      The median follow-up in these 25 patients is 36 months (12 to 75 months). Twenty
      patients have had no evidence of local recurrence following their primary
      treatment (FFR = 80%). A multivariate analysis using stepwise logistic regression
      was used to predict failure in 3 years or less. Potential predictors examined
      included age, sex, tumor location, primary versus recurrent disease, grade,
      histology, surgical margins, implant only versus implant plus external beam, and
      a ratio of the volume of tissue which received 65 Gy (TV65) to the tumor volume
      (TV), that is (TV65/TV). The single variable which was significantly associated
      with local failure by 3 years was a TV65/TV of less than one. Once this variable
      was entered into the analysis, no other factor proved statistically significant.
      Our data suggest that when attempting local control of soft tissue sarcomas with
      brachytherapy, the volume of tissue receiving 65 Gy (TV65) from both implant and
      external beam must exceed the volume of the excised lesion (TV). Since the volume
      of a tumor can be readily determined prior to surgical excision either by CT or
      MRI scanning, pre-planning of the implant volume could potentially reduce the
      rate of local failure.

PMID- 1995548
TI  - Physical aspects of total body irradiation of bone marrow transplant patients
      using 18 MV x rays.
AB  - The physical aspects of a total body irradiation (TBI) treatment are described.
      Patients seated in a special chair with their legs bent backwards are irradiated
      anteriorly and posteriorly (AP/PA). The chair reduces patient movement and
      facilitates positioning patients during 9 fractions of TBI over a 3-day period.
      The dose to lower extremities are monitored and raised to the total body dose. A
      conventional linear accelerator in a standard size treatment room is used to
      deliver 18 MV x-ray beams at a dose rate of approximately 20 cGy/min at a 350 cm
      treatment distance. Results of dose distribution, field flatness, dose
      uniformity, in vivo and in vitro dosimetry, and boost irradiation techniques are
      described.

PMID- 1995546
TI  - Blood flow of human soft tissue sarcomas measured by thallium-201 scanning:
      prediction of tumor response to radiation.
AB  - Thallium-201 chloride (201T1) has been used to determine regional perfusion in
      the myocardium and in tumors. This study was done to determine the potential
      prognostic importance of lesion tracer uptake to regression, local control, and
      rate of distant metastasis in 14 patients with neoplasms of soft tissue. Most
      patients had planned resections following preoperative radiation therapy. Minimum
      follow-up was 4 years. The ratio of nuclide uptake in the tumor to surrounding
      normal tissue was used as an estimate of relative blood flow. Tumors with acute
      volume responses (greater than or equal to 50% at the completion of X
      irradiation) had lower 201T1 uptake indicating lower relative blood flow than
      tumors that failed to have a volume reduction [1.63 +/- 0.30 (n = 9) vs 3.49 +/-
      0.41 (n = 5) 201T1]. All patients had local tumor control. Patients with high
      uptake tumors tended to develop metastases at a higher frequency, although this
      was not statistically significant (p = 0.10). We conclude that 201T1 scans are a
      safe, non-invasive method of estimating tumor perfusion which can be useful to
      predict acute response to radiation, and may help to identify patients who will
      ultimately develop distant metastases.

PMID- 1995549
TI  - A method to analyze 2-dimensional daily radiotherapy portal images from an on
      line fiber-optic imaging system.
AB  - On-line radiotherapy imaging systems allow convenient treatment verification and
      generate a wealth of data. Quantitative analysis of data will provide important
      information about the nature of treatment variations. Using an inhouse fiber
      optic imaging system to acquire daily portal images for five patients, we have
      developed a method to analyze the cumulative positional variation of blocks in
      the 2-dimensional images. For each beam arrangement used to treat a particular
      patient, a reference portal image was established. All other images for that
      patient were registered with respect to the anatomical landmarks visible on the
      reference image. Two-dimensional frequency distributions describing the overlap
      of the blocks during the course of treatment were then calculated and
      superimposed on the reference image. Results of the analysis show positional and
      quantitative information about the daily variation in block placement, and
      appeared to be site-dependent. Long term verification studies using on-line
      imaging systems will be important in the understanding of treatment
      uncertainties.

PMID- 1995547
TI  - Relocatable frame for stereotactic external beam radiotherapy.
AB  - A non-invasive head fixation system is described which is accurately relocatable
      and enables the transfer of stereotactic positions between a variety of
      radiodiagnostic images and therapeutic procedures. The system can be simply and
      repeatedly applied for planning stereotactic radiation therapy from one or more
      diagnostic images and for repeated treatment with a conventional linear
      accelerator. In addition, the long-term effects of therapy can be objectively
      monitored by relocating the frame and repeating images in an identical way,
      months or years later.

PMID- 1995551
TI  - Reduction in radiation exposure to nursing personnel with the use of remote
      afterloading brachytherapy devices.
AB  - The radiation exposure to nursing personnel from patients with brachytherapy
      implants on a large brachytherapy service were reviewed. Exposure to nurses, as
      determined by TLD monitors, indicates a 7-fold reduction in exposure after the
      implementation of the use of remote afterloading devices. Quarterly TLD monitor
      data for six quarters prior to the use of remote afterloading devices demonstrate
      an average projected annual dose equivalent to the nurses of 152 and 154 mrem
      (1.5 mSv). After the implementation of the remote afterloading devices, the
      quarterly TLD monitor data indicate an average dose equivalent per nurse of 23
      and 19 mrem (0.2 mSv). This is an 87% reduction in exposure to nurses with the
      use of these devices (p less than 0.01).

PMID- 1995550
TI  - A new device for interstitial 125Iodine seed implantation.
AB  - A new device for interstitial implantation of I125 seeds is presented. The
      technical details and function of the system are described and compared with well
      known commercial systems. Its unique design allows for simple, fast, and safe
      treatment of most tumor sites including stereotactic implantation of brain.
      Radiation measurements indicate low exposure to both patients and personnel
      during implantation.

PMID- 1995553
TI  - Future analyses of total body irradiation.

PMID- 1995552
TI  - What does total body irradiation do in bone marrow transplants for leukemia?

PMID- 1995554
TI  - Long-term follow-up of Ewing's sarcoma of bone.

PMID- 1995555
TI  - Hypoxia: new mechanisms for old?

PMID- 1995556
TI  - Response to Vriesendorp et al.

PMID- 1995557
TI  - Response to Adams.

PMID- 1995558
TI  - Iron toxicosis in cattle.

PMID- 1995559
TI  - Education vs advertising.

PMID- 1995560
TI  - Cystinuria in a cat.
AB  - A 10-month-old male Siamese cat with dysuria was determined to have cystine
      crystalluria. Many small calculi composed entirely of cystine were found in the
      urinary bladder. Measurement of serum and urine amino acids and calculation of
      fractional reabsorption of amino acids indicated reabsorption defects for
      cystine, ornithine, lysine, and arginine. Urinary acidification, fractional
      reabsorption of glucose, and fractional reabsorption of electrolytes were normal.
      Diagnoses of cystinuria and cystine urolithiasis were made on the basis of low
      fractional reabsorption of cystine and dibasic amino acids and the detection of
      cystine calculi in the urinary bladder.

PMID- 1995561
TI  - Ataxia in a kitten treated with griseofulvin.
AB  - A 12-week-old male domestic shorthair kitten developed ataxia, fever, leukopenia,
      and thrombocytopenia during treatment with griseofulvin for superficial
      dermatophytosis. The fever and hematologic changes resolved promptly with
      withdrawal of the drug, but the ataxia continued unchanged. Persistent ataxia may
      represent a previously unrecognized idiosyncratic reaction to griseofulvin in
      cats.

PMID- 1995562
TI  - Beta-mannosidosis in twelve Salers calves.
AB  - A diagnosis of beta-mannosidosis, a lysosomal storage disease caused by a
      deficiency of beta-mannosidase, was made in 12 purebred Salers calves. Affected
      neonatal calves were unable to rise and had intention tremors, hidebound skin,
      slightly domed calvaria, slight prognathism, and narrow palpebral fissures.
      Postmortem findings included variable dilatation of the lateral cerebral
      ventricles, marked pallor and paucity of white matter of the cerebrum and
      cerebellum, and mild to marked bilateral renomegaly. Microscopic lesions
      consisted of clear, intracytoplasmic vacuoles, which were especially prominent in
      neurons, thyroid follicular cells, proximal renal tubular epithelium, and
      reticuloendothelial cells. By ultrastructural examination, the intracytoplasmic
      vacuoles were identified as membrane-bound lysosomes distended by lucent
      material. The serum of affected calves was profoundly deficient in beta
      mannosidase. Oligosaccharides, principally a trisaccharide with a terminal hexose
      in the beta-anomeric configuration, accumulated in tissues of affected calves.
      The percentage (37.2) of affected calves from groups of siblings, the
      approximately equal sex ratio, and the phenotypic normalcy of the parents of
      affected calves are compatible with an autosomal recessive mode of inheritance
      typical of other glycoproteinoses.

PMID- 1995563
TI  - Thyroid function testing in dogs.

PMID- 1995564
TI  - Accuracy of references.

PMID- 1995566
TI  - Severe masseter myonecrosis in a horse.
AB  - A 6-year-old Quarter Horse was examined because of acute, severely swollen
      masseter muscles (palpation of which elicited pain response), exophthalmos,
      severe chemosis, and protrusion of the third eyelids. Blood selenium and vitamin
      E concentrations, and results of feed analysis and muscle biopsy supported a
      diagnosis of nutritional myopathy. The horse was treated and was clinically
      normal 2 weeks after discharge from the hospital.

PMID- 1995565
TI  - Bleeding disorder (von Willebrand disease) in a quarter horse.
AB  - Bleeding diathesis in a Quarter Horse filly was caused by von Willebrand disease.
      Hemorrhage occurred mainly from mucosal surfaces and after trauma. Quantitative
      and qualitative measurements of plasma von Willebrand factor (vWF) documented a
      specific deficiency of vWF high molecular weight multimers, and concurrently
      greater than expected deficiency of vWF activity relative to vWF concentration.
      These findings are characteristic of type-II von Willebrand disease in human
      beings. Application of vWF assays used in human and small animal medicine now
      permits evaluation of vWF and diagnosis of von Willebrand disease in horses with
      bleeding disorders.

PMID- 1995567
TI  - Disruption of the caudal component of the reciprocal apparatus in two horses.
AB  - Two horses became acutely lame following a fall during strenuous exercise and
      were diagnosed as having disruption of the caudal component of the reciprocal
      apparatus. Clinical signs consisted of lameness of the right pelvic limb,
      characterized by flexion of the hock and simultaneous extension of the stifle.
      Radiography revealed an avulsion fracture from the supracondylar tuberosity and
      fossa of the distal portion of the femur in one horse. Clinical and radiographic
      findings indicated avulsion of the lateral origin of the gastrocnemius and
      superficial digital flexor muscles. Treatment consisted of stall rest, limb
      immobilization, and phenylbutazone administration. One horse recovered to
      soundness and the other deteriorated and was euthanatized.

PMID- 1995568
TI  - Severe hypercarbia resulting from inspiratory valve malfunction in two
      anesthetized horses.
AB  - Severe hypercarbia was documented by arterial blood gas analysis in 2 adult
      horses anesthetized for exploratory laparotomy. Both horses appeared to be
      adequately anesthetized, but continued to breathe against the ventilator. In both
      cases, the inspiratory valve on the anesthesia machine was found to be stuck
      open, permitting expired CO2 to return to the inspiratory limb of the anesthetic
      circuit and to be inhaled with the next breath. Correction of the malfunctioning
      valve alleviated the hypercarbia. Problems with the flow valves of the anesthesia
      machine should be suspected when anesthetized horses breathe against the
      ventilator and develop severe hypercarbia.

PMID- 1995569
TI  - Clinical and epidemiologic features of an epizootic of equine
      leukoencephalomalacia.
AB  - A herd of 15 mature riding horses with a history of anorexia, weight loss, and
      lethargy was examined. The animals had been fed a 50/50 mixture of commercial
      sweet feed and corn screenings contaminated with a heavy growth of Fusarium
      moniliforme. Thirteen of the horses had one or more neurologic signs. The most
      characteristic signs were profound depression and mild ataxia. Over the 19-day
      course of the epizootic, the horses had increasing severe neurologic deficits,
      including unilateral blindness and delirium. Despite the clinical appearance of
      dehydration, 12 horses had low PCV (16 to 27%), hematocrit (21.2 to 31.0%;
      determined by automated cell counter), and RBC counts (3.76 to 5.5 x 10(6)
      RBC/microliters). White blood cell counts were variable (4,900 to 17,000
      WBC/microliters). Necropsy findings included diffuse malacia of the white matter
      of the frontal cortex and severe multifocal perivascular hemorrhage in the white
      matter of the temporal cortex, basal ganglia, anterior medulla, and pons. One
      horse had a hepatic lesion consisting of a mixed inflammatory cell infiltrate and
      bile duct proliferation. The attack rate of this epizootic was 100%. The course
      of disease was unusually long in some animals. In an experiment, the fusarium
      infected corn screenings were fed to horses and did not cause clinical signs or
      alterations in blood or serum biochemical values.

PMID- 1995570
TI  - Factor XII and partial prekallikrein deficiencies in a dog with recurrent
      gastrointestinal hemorrhage.
AB  - Factor XII deficiency and impaired prekallikrein activity were diagnosed in a 1
      year-old Chinese Shar Pei. The dog experienced repeated episodes of intestinal
      hemorrhage and diarrhea. Laboratory findings were compatible with blood loss
      (iron deficiency anemia and hypoproteinemia). Necropsy findings suggested mild
      infiltrative bowel disease that could have been responsible for the dog's
      diarrhea, but no explanation for the severe recurrent gastrointestinal hemorrhage
      could be found. Factor XII deficiency is uncommon in the dog and is not
      associated with hemorrhagic tendencies. The factor XII deficiency in this case
      may have contributed to the gastrointestinal hemorrhage.

PMID- 1995572
TI  - Transfixation pinning and casting of tibial fractures in calves: five cases (1985
      1989).
AB  - Medical records of 5 calves with tibial fractures that were reduced and
      stabilized by transfixation pinning and casting were reviewed. Multiple Steinmann
      pins were placed transversely through proximal and distal fracture fragments, and
      the pin ends were incorporated in fiberglass cast material after fracture
      reduction. Cast material serves as an external frame to maintain pin position and
      fracture reduction. Calves were between 2 weeks and 6 months old and weighed
      between 40 and 180 kg. Three fractures were spiral in configuration and 2 were
      comminuted. One tibial fracture was open. After surgery, all calves were
      ambulatory within 24 hours. To improve tarsal flexion and achieve normal stance
      in 3 calves, cast revision was required on the caudal aspect of the limb. Good
      radiographic and clinical evidence of stability was observed in 5 to 10 weeks
      (mean 8 weeks), at which time the pis and cast were removed. Return to normal
      function was rapid and judged to be excellent at follow-up evaluation 3 to 12
      months later. Advantages of transfixation pinning and casting in management of
      tibial fractures include flexibility in pin positioning, adequate maintenance of
      reduction, early return to weight-bearing status, joint mobility, and ease of
      ambulation. The inability to adjust fixation and alignment after cast application
      is a disadvantage of this technique compared with other external fixators.

PMID- 1995573
TI  - Storage of expensive anticancer drugs.

PMID- 1995571
TI  - Histopathologic study of uveitis in cats: 139 cases (1978-1988).
AB  - Histopathologic findings in 158 globes obtained from 139 cats by enucleation or
      at necropsy, with histopathologic diagnosis of uveitis, were compared, and
      morphology was correlated with clinical and/or histopathologic diagnosis. The
      most common morphologic feature was a lymphocytic-plasmacytic anterior uveal
      infiltrate that was either diffuse or nodular; specific cause could not be
      associated with this nongranulomatous anterior uveitis. In decreasing order of
      frequency, other common causes of uveitis in cats included feline infectious
      peritonitis; FeLV-associated lymphosarcoma; trauma; and lens-induced uveitis.

PMID- 1995575
TI  - Disability benefits expanded in AVMA basic protection package.

PMID- 1995576
TI  - Compendium of animal rabies control, 1991. National Association of State Public
      Health Veterinarians, Inc.

PMID- 1995574
TI  - What is your diagnosis? Radiolucent defect within the soft tissues immediately
      plantar and proximal to the navicular bone.

PMID- 1995578
TI  - The challenge of foreign service.

PMID- 1995577
TI  - Feeding the world in the 1990s and beyond: a role for veterinary medicine.

PMID- 1995579
TI  - Statistics simplified. Comparing means.

PMID- 1995580
TI  - ECG of the month.

PMID- 1995581
TI  - Veterinary medical records--some legal considerations.

PMID- 1995582
TI  - Soft tissue- and bone-phase scintigraphy for diagnosis of navicular disease in
      horses.
AB  - Radiography and soft tissue- and bone-phase scintigraphy were performed on 14
      clinically normal horses and 35 horses in which definite, probable, or possible
      navicular disease had been diagnosed. The specificity of radiography and
      scintigraphy in revealing signs of navicular disease were nearly equal; however,
      the sensitivity of scintigraphy appeared to be greater than that of radiography.
      The greatest sensitivity and specificity were achieved when the results of
      radiography and scintigraphy were evaluated together. Differences in sensitivity
      were greatest when scintigraphy revealed lesions not detected by radiography.
      Although a diagnosis of navicular disease was sometimes made when only soft
      tissue-phase or only bone-phase scintigraphy revealed lesions, results obtained
      during the 2 phases generally were similar. It was concluded that scintigraphy
      can be a valuable aid in diagnosing navicular disease in horses, especially when
      radiographic findings do not support clinical findings.

PMID- 1995583
TI  - Relationship of strain 19 calfhood vaccination in beef herds and brucellosis
      reactor rates, duration of quarantine, and number of herd tests.
AB  - Initial and cumulative reactor rates for strain 19 vaccinates and nonvaccinates
      were significantly (P less than 0.001) lower for beef herds containing variable
      proportions of vaccinates, compared with reactor rates in nonvaccinated herds. In
      addition, significant (P less than 0.005) reduction in cumulative incidence was
      observed in nonvaccinated and strain 19-vaccinated cattle as the proportion of
      vaccinates within the herd increased from 1 to 19%, 20 to 39%, 40 to 59%, and 60
      to 100%. Duration of quarantine and number of herd tests were not reduced in
      herds with strain 19-vaccinated cattle. In herds released from quarantine,
      duration of quarantine and number of tests were positively correlated to
      proportion of the herd vaccinated. In nonvaccinated herds released from
      quarantine, effect of herd size was documented by strong positive (P = 0.042)
      correlation with duration of quarantine and slightly weaker correlation (P =
      0.095) with number of tests.

PMID- 1995584
TI  - Erythrocyte dyscrasia, anemia, and hypothyroidism in chronically underweight
      llamas.
AB  - A syndrome characterized by anemia, erythrocyte dyscrasia, low body weight, and
      hypothyroidism was observed in 8 llamas (Lama glama). At initial examination (1
      to 23 months of age; median, 7.5 months), llamas (3 males, 5 females) were
      markedly underweight (29 to 55 kg; median, 36 kg) and anemic (PCV, 12.9 to 25.5%
      [median, 19%]). Five of the llamas became progressively more anemic over time; in
      2 of them, PCV decreased to less than 10%. Erythrocyte changes included severe
      poikilocytosis, anisocytosis, asymmetric distribution of hemoglobin within the
      cytoplasm, and cytoplasmic extensions from one or both poles. Six llamas had
      moderate to severe valgus deformities of the carpus. All llamas had low baseline
      serum thyroxine concentration and diminished response to thyrotropin
      administration. Baseline and post-thyrotropin triiodothyronine concentrations did
      not have consistent patterns. Five llamas were hypophosphatemic and 7 had low
      serum iron concentration (iron concentration was not determined in 1 llama).
      Orally administered iron supplementation did not induce clinical improvement.
      Because 3 of the affected llamas were full sisters, a genetic basis for the
      problem has to be considered. It was not possible to evaluate the familial
      relationship of the other 5 affected llamas. Although the underlying cause of the
      problem was not established, the prognosis for affected llamas is guarded to
      poor.

PMID- 1995586
TI  - Safety and efficacy of ivermectin against ear mites (Otodectes cynotis) in ranch
      foxes.
AB  - Efficacy of ivermectin at a dosage of 0.2 mg/kg of body weight was evaluated
      against naturally acquired ear mite (Otodectes cynotis) infestation in
      commercially raised ranch foxes (Vulpes fulva). Efficacy of ivermectin given sc
      twice at 3-week intervals was 97.4%. Toxicosis associated with drug treatment was
      not observed. Increased dosage of 1.0 mg/kg was given sc to 5 foxes each week for
      6 consecutive weeks, and signs of toxicosis or illness were not observed after
      treatment.

PMID- 1995585
TI  - Evaluation of craniotomy in dogs and cats.
AB  - Over a reporting period of 5 years, craniotomy was performed in 26 dogs and 5
      cats with various intracranial lesions. X-ray computed tomography was performed
      in all animals prior to surgery. Twenty dogs and all cats had intracranial
      neoplasms; of these, 14 were meningioma, and 11 represented a wide variety of
      brain tumors and skeletal tumors. Three dogs were treated surgically for
      traumatic, open-skull fractures with cerebral damage, and 3 underwent biopsy to
      evaluate chronic inflammatory brain disease. The overall medium survival time was
      212 days, the 1-year survival rate was 39%, and the 2-year survival rate was 20%.
      Dogs and cats with meningioma survived a mean 198 and 485 days, respectively,
      with 1-year survival rates of 30% for dogs and 50% for cats. The overall median
      survival time for animals with tumors other than meningeal intracranial neoplasms
      was 414 days, with a 1-year survival rate of 40%. The death of 19% of all animals
      could be related to the combination of advanced brain disease and surgery.
      Because fatality seldom occurred as a direct result of surgery, morbidity and
      mortality associated with craniotomy in pet animals can be seen as acceptably
      low. In 29 of 34 craniotomies, dura mater defects were left unsutured and no
      adverse effects were seen.

PMID- 1995587
TI  - Chronic copper poisoning in sheep grazing pastures fertilized with swine manure.
AB  - Several pregnant ewes developed an acute hemolytic crisis and died. Liver and
      kidney copper concentrations were high, confirming chronic copper poisoning as
      the cause of death. Feed and water samples that the affected ewes had been
      consuming did not contain excess copper. Because swine manure slurry had been
      applied to the pasture where the sheep had grazed, a copper analysis was
      conducted on soil and forage samples from this field. High copper concentrations
      were detected in the soil and forage samples from the slurry pasture. Most sheep
      producers are aware of the catastrophic consequences that result when feeds
      containing copper and insufficient amounts of molybdenum are fed to sheep.
      However, producers and veterinarians often are unaware of some of the subtle
      sources of copper. Most of the copper that is added to swine and poultry feeds as
      growth promotants passes through the gastrointestinal tract unabsorbed and
      remains in the waste material. Pastures that have copper-containing waste
      material, but no molybdenum applied, can produce the same fatal results as giving
      sheep feed supplemented with copper but containing no molybdenum.

PMID- 1995588
TI  - A family of regulatory genes associated with type II restriction-modification
      systems.
AB  - Restriction-modification systems must be regulated to avoid autorestriction and
      death of the host cell. An open reading frame (ORF) in the PvuII restriction
      modification system appears to code for a regulatory protein from a previously
      unrecognized family. First, interruptions of this ORF result in a nonrestricting
      phenotype. Second, this ORF can restore restriction competence to such
      interrupted mutants in trans. Third, the predicted amino acid sequence of this
      ORF resembles those of known DNA-binding proteins and includes a probable helix
      turn-helix motif. A survey of unattributed ORFs in 15 other type II restriction
      modification systems revealed three that closely resemble the PvuII ORF. All four
      members of this putative regulatory gene family have a common position relative
      to the endonuclease genes, suggesting a common regulatory mechanism.

PMID- 1995589
TI  - Cloning and nucleotide sequences of lux genes and characterization of luciferase
      of Xenorhabdus luminescens from a human wound.
AB  - Xenorhabdus luminescens HW is the only known luminous bacterium isolated from a
      human (wound) source. A recombinant plasmid was constructed that contained the X.
      luminescens HW luxA and luxB genes, encoding the luciferase alpha and beta
      subunits, respectively, as well as luxC, luxD, and a portion of luxE. The
      nucleotide sequences of these lux genes, organized in the order luxCDABE, were
      determined, and overexpression of the cloned luciferase genes was achieved in
      Escherichia coli host cells. The cloned luciferase was indistinguishable from the
      wild-type enzyme in its in vitro bioluminescence kinetic properties. Contrary to
      an earlier report, our findings indicate that neither the specific activity nor
      the size of the alpha (362 amino acid residues, Mr 41,389) and beta (324 amino
      acid residues, Mr 37,112) subunits of the X. luminescens HW luciferase was
      unusual among known luminous bacterial systems. Significant sequence homologies
      of the alpha and beta subunits of the X. luminescens HW luciferase with those of
      other luminous bacteria were observed. However, the X. luminescens HW luciferase
      was unusual in the high stability of the 4a-hydroperoxyflavin intermediate and
      its sensitivity to aldehyde substrate inhibition.

PMID- 1995590
TI  - Overlapping mRNA transcripts of photosynthesis gene operons in Rhodobacter
      capsulatus.
AB  - The crtEF, bchCA, and puf operons of the facultative phototrophic bacterium
      Rhodobacter capsulatus encode gene products that are necessary for the formation
      of various components of the photosynthetic apparatus. The crtEF operon encodes
      two enzymes involved in the biosynthesis of carotenoids, the bchCA operon codes
      for two enzymes of the bacteriochlorophyll biosynthetic pathway, and the puf
      operon encodes four pigment-binding polypeptides as well as two polypeptides with
      less well understood functions. These three operons are adjacent to one another
      on the chromosome and are transcribed in the same direction. We present the
      results of RNA blotting and S1 nuclease protection end-mapping experiments which
      provide direct evidence that the mRNA transcripts of these three operons overlap.
      Therefore, it is likely that the crtEF, bchCA, and puf operons can be expressed
      as a single transcriptional unit, although RNA polymerase may initiate
      transcription at any of several promoters.

PMID- 1995592
TI  - Effects of translation on degradation of mRNA segments transcribed from the
      polycistronic puf operon of Rhodobacter capsulatus.
AB  - Previous work has shown that expression of genes within the polycistronic puf
      operon of Rhodobacter capsulatus is regulated in part by differential degradation
      of segments of puf transcripts. To understand the role of ribosome coverage in
      the differential stability of puf mRNA segments, we have studied the effects of
      mutations that alter translation of specific puf transcript segments on puf mRNA
      decay. Our results show that stopping translation either within the light
      harvesting I (LHI) genes or near the 5' end of the reaction center (RC)-coding
      region decreased the stability of puf transcript segments downstream from a
      hairpin loop structure located between the LHI and RC genes but failed to affect
      the upstream sequences so long as the loop was present. Mutations that allowed
      translation to proceed through the hairpin structure reduced its ability to
      protect upstream sequences from accelerated decay. Introduction of translation
      stops more than 107 bp into the RC-coding region, but still 5' to an mRNA segment
      containing decay-promoting endonuclease cleavage sites, had no effect on puf mRNA
      stability. The divergent and location-dependent consequences of translation stops
      imply that different mechanisms are responsible for the degradation of different
      puf mRNA segments and indicate that coverage of puf mRNA sequences by ribosomes
      is insufficient and may in some cases be unnecessary to protect these sequences
      from degradation.

PMID- 1995591
TI  - Salmonella typhimurium histidine periplasmic permease mutations that allow
      transport in the absence of histidine-binding proteins.
AB  - Periplasmic transport systems consist of a membrane-bound complex and a
      periplasmic substrate-binding protein and are postulated to function by
      translocating the substrate either through a nonspecific pore or through specific
      binding sites located in the membrane complex. We have isolated mutants carrying
      mutations in one of the membrane-bound components of the histidine permease of
      Salmonella typhimurium that allow transport in the absence of both histidine
      binding proteins HisJ and LAO (lysine-, arginine-, ornithine-binding protein).
      All of the mutations are located in a limited region of the nucleotide-binding
      component of the histidine permease, HisP. The mutants transported substrate in
      the absence of binding proteins only when the membrane-bound complex was produced
      in large amounts. At low (chromosomal) levels, the mutant complex was unable to
      transport substrate in the absence of binding proteins but transported it
      efficiently in the presence of HisJ. The alterations responsible for the
      mutations were identified by DNA sequencing; they are closely related to a group
      of hisP mutations isolated as suppressors of HisJ interaction mutations (G. F.-L.
      Ames and E. N. Spudich, Proc. Natl. Acad. Sci. USA 73:1877-1881, 1976). The hisP
      suppressor mutations behaved similarly to these newly isolated mutations despite
      the entirely different selection procedure. The results are consistent with the
      HisP protein carrying or contributing to the existence of a substrate-binding
      site that can be mutated to function in the absence of a binding protein.

PMID- 1995593
TI  - Thioredoxin elicits a new dihydrolipoamide dehydrogenase activity by interaction
      with the electron-transferring flavoprotein in Clostridium litoralis and
      Eubacterium acidaminophilum.
AB  - The glycine-utilizing bacterium Clostridium litoralis contained two enzyme
      systems for oxidizing dihydrolipoamide. The first one was found to be a genuine
      dihydrolipoamide dehydrogenase, present only in low amounts. This enzyme had the
      typical dimeric structure with a subunit molecular mass of about 53 kDa; however,
      it reacted with both NADP (Km 0.11 mM) and NAD (Km 0.5 mM). The reduction of
      pyridine nucleotides by dihydrolipoamide was the strongly preferred reaction. A
      second dihydrolipoamide-oxidizing enzyme system consisted of the interaction of
      two proteins, the previously described NADP(H)-dependent electron-transferring
      flavoprotein (D. Dietrichs, M. Meyer, B. Schmidt, and J. R. Andreesen, J.
      Bacteriol. 172:2088-2095, 1990) and a thioredoxin. This enzyme system was
      responsible for most of the dihydrolipoamide dehydrogenase activity in cell
      extracts. The thioredoxin did not bind to DEAE, was heat stable, and had a
      molecular mass of about 15 kDa. N-terminal amino acid analysis of the first 38
      amino acid residues resulted in 38% homology to Escherichia coli thioredoxin and
      about 76% homology to a corresponding protein isolated from the physiologically
      close related Eubacterium acidaminophilum. The protein of the latter organism had
      a molecular mass of about 14 kDa and stimulated the low dihydrolipoamide
      dehydrogenase activity of the corresponding flavoprotein. By this interaction
      with NADPH-dependent flavoproteins, a new assay system for thioredoxin was
      established. A function of thioredoxin in glycine metabolism of some anaerobic
      bacteria is proposed.

PMID- 1995594
TI  - Complete nucleotide sequences and comparison of the structural genes of two 2
      haloalkanoic acid dehalogenases from Pseudomonas sp. strain CBS3.
AB  - The nucleotide sequences of two DNA segments from Pseudomonas sp. strain CBS3
      that code for two different haloalkanoic acid halidohydrolases were determined.
      Two open reading frames with coding capacities of 227 amino acids (corresponding
      to a molecular mass of 25,401 Da) and 229 amino acids (corresponding to a
      molecular mass of 25,683 Da) were identified as structural genes of 2
      haloalkanoic acid dehalogenases I (dehCI) and II (dehCII) by comparison with the
      N-terminal amino acid sequences of these enzymes. Comparison of the two sequences
      revealed 45% homology on the DNA level and 37.5% homology on the amino acid
      level. No homology with other known protein or nucleotide sequences was found.

PMID- 1995595
TI  - Expression of gene 1.2 and gene 10 of bacteriophage T7 is lethal to F plasmid
      containing Escherichia coli.
AB  - Plasmids expressing bacteriophage T7 gene 1.2 or gene 10 DNA transform F plasmid
      containing strains of Escherichia coli only at low efficiency, though they
      transform plasmid-free strains normally. The gene products T7 gp1.2 and T7 gp10
      appear to be the toxic agents, and their effects are directed towards the product
      of the F pifA gene, PifA. T7 gp1.2 and gp10 are also the two targets of the pif
      exclusion system of F, and their synthesis normally triggers the abortive
      infection of T7 in pifA+ hosts. The properties of plasmids containing T7 gene 1.2
      or 10 suggest that they can be used to study the molecular mechanisms of phage
      exclusion in model systems that avoid the pleiotropic dysfunctions associated
      with an abortive infection.

PMID- 1995596
TI  - In situ assay of ribulose-1,5-bisphosphate carboxylase/oxygenase in Thiobacillus
      neapolitanus.
AB  - Cells permeabilized with chloroform yielded ribulose-1,5-bisphosphate
      carboxylase/oxygenase (RuBisCO) activities nearly equal to those of cell
      extracts, thus indicating that both cytoplasmic and carboxysomal RuBisCO are
      functional in situ. The carboxysomal and cytoplasmic RuBisCO both form the CO2
      Mg2(+)-enzyme ternary complex, as evidenced by stabilization with 2-C-carboxy-D
      arabinitol-1,5-bisphosphate (CABP), a potent competitive inhibitor of RuBisCO.
      The data are consistent with the hypothesis that the carboxysome is functional in
      carbon dioxide fixation.

PMID- 1995597
TI  - Lessons to be learned from long-term treatment of affective disorders: potential
      utility in panic disorder.
AB  - Although the research on long-term treatment for panic disorder is in an early
      stage, there is a considerable body of data on affective disorders. The author
      discusses three long-term projects pertinent to affective disorders, with the
      idea that they may suggest possible avenues of research in the field of panic
      disorder: (1) the MacArthur Foundation task force arrives at consensus
      definitions and proposes tentative operational criteria; (2) the National
      Institute of Mental Health Collaborative Study compares the effects of lithium
      carbonate, imipramine, the lithium/imipramine combination, and placebo in
      preventing the recurrence of affective disorders; and (3) the Pittsburgh Study
      explores the efficacy of the combination of imipramine and interpersonal
      psychotherapy as a preventive strategy against recurrence of depression.

PMID- 1995598
TI  - Long-term pharmacologic treatment of panic disorder.
AB  - In this paper, the author reviews the existing knowledge regarding the long-term
      treatment of panic disorder, including extensive clinical experience and data
      available from controlled studies. He conceptualizes long-term treatment in four
      phases--acute, stabilization, maintenance, and discontinuation--and in discussing
      these phases, outlines specific treatment goals for each of them. He presents
      measures for the management of withdrawal symptoms and relapse, focusing on the
      use of a slow taper over 3 to 6 months. The author then reviews the limited data
      currently available on long-term treatment outcome, including comparisons of 2
      and 8 months of treatment demonstrating greater improvements with the longer
      treatment, and presents follow-up data 3 to 6 years after pharmacologic
      treatment. From clinical and research experience, he concludes that longer-term
      treatment of panic disorder is indicated for full recovery, although further
      studies are needed.

PMID- 1995600
TI  - Panic disorder: strategies for long-term treatment.
AB  - Issues in the treatment of panic disorder now focus on long-term maintenance
      treatment with medication. The author sets the stage for our current
      understanding of panic disorder by describing the historical development of our
      knowledge of this disorder, past and current psychiatric diagnostic systems, and
      the symptoms of panic disorder. He states that this supplement reviews much of
      the great amount of research done on panic disorder in the 1980s and concludes
      with descriptions of each of the papers in this supplement.

PMID- 1995599
TI  - Decisions for the clinician in the treatment of panic disorder: when to treat,
      which treatment to use, and how long to treat.
AB  - Issues in clinicians' decisions about initiation, selection, and duration of
      treatment for patients with panic disorder are reviewed. Panic disorder may
      entail considerable morbidity, particularly if left untreated. This observation,
      coupled with clinical experience that the benefits of pharmacologic treatment
      generally outweigh their risks, suggests that patients with panic disorder should
      be treated with medication. A decision tree for the acute and maintenance
      treatment of panic disorder patients is presented, and possible indications for
      both acute and maintenance treatments are discussed. The advantages and
      disadvantages of treatment with each of the three classes of drugs that have been
      found effective for panic disorder--the tricyclic antidepressants, the monoamine
      oxidase inhibitors, and the benzodiazepines--are reviewed.

PMID- 1995601
TI  - Panic disorder: impact on quality of life.
AB  - The author reviews selected data from the Epidemiologic Catchment Area study of a
      probability sample of over 18,000 adults living in five U.S. communities. The
      data indicate that panic disorder, like major depression, is associated with
      impairments in quality of life. These impairments need to be considered in
      planning treatment and evaluating the efficacy of its outcome.

PMID- 1995602
TI  - Alteration of high and low spin equilibrium by a single mutation of amino acid
      209 in mouse cytochromes P450.
AB  - The identities of the amino acid at position 209 are most critical in determining
      specific coumarin 7- and steroid 15 alpha-hydroxylase activity in P450coh and
      P450(15)alpha, respectively. This system, therefore, provides us with an
      excellent model to study the structural basis for P450 specificity as a
      monooxygenase. We expressed in Saccharomyces cerevisiae a series of the mutated
      P450s in which residue 209 was substituted with the various amino acids and
      characterized the spectral property and hydroxylase activity of these mutated
      P450s. The positioning of a hydrophobic residue including Phe, Leu, and Val at
      position 209 resulted in shifting the P450 to the high-spin state, while a
      charged amino acid such as Lys or Asp produced the low-spin form. Moreover, a
      P450 with Asn or Gly in this position exhibited spectra indicating a mixture of
      the high- and low-spin forms. This spin alteration, depending upon the
      hydrophobicity and size of residue at position 209, indicates that this position
      is likely to reside close to the sixth axial ligand on the distal surface of the
      heme in these P450s. This proximity of residue 209 to the ligand may explain the
      critical role of this residue in determining the hydroxylase specificity and
      activity of these P450s.

PMID- 1995603
TI  - A de novo designed signal peptide cleavage cassette functions in vivo.
AB  - Leader peptidase (Lep) is a membrane-bound enzyme of the Escherichia coli inner
      membrane that serves to remove signal peptides from exported proteins.
      Statistical and experimental studies of known signal peptides have defined a
      short C-terminal region that seems to provide the information for correct
      cleavage by Lep. Based on the patterns of conserved amino acids found in this
      region, we have designed a signal peptide "cleavage cassette." This cassette is
      processed at the expected site when introduced after an uncleaved signal peptide.
      Furthermore, processing is blocked in the predicted manner when the (-3, -1)-rule
      for signal peptide cleavage is violated. This suggests that current understanding
      of the sequence requirements for signal peptide cleavage is sufficiently advanced
      to be used in, e.g. protein engineering applications.

PMID- 1995604
TI  - Regulation of cholesterol 7 alpha-hydroxylase mRNA and transcriptional activity
      by taurocholate and cholesterol in the chronic biliary diverted rat.
AB  - Cholesterol 7 alpha-hydroxylase catalyzes the rate-limiting step in the bile acid
      biosynthetic pathway. Regulation of this pathway is thought to occur solely as a
      result of a negative feedback control mechanism that is dependent upon the flux
      and composition of bile salts undergoing enterohepatic circulation. We have used
      the chronic biliary diverted (CBD) rat model to study the mechanism of regulation
      of cholesterol 7 alpha-hydroxylase by taurocholate. As compared to nonoperated
      controls, CBD rats exhibited a 4.2-fold increase in cholesterol 7 alpha
      hydroxylase-specific activity, a 4.5-fold increase in enzyme mass, a 10-fold
      increase in steady-state mRNA levels, and a 3.4-fold increase in transcriptional
      (nuclear "run-on") activity. Intraduodenal infusion of taurocholate at a rate of
      36 mumol/100 g/h for 48 h in CBD rats caused a significant (p less than 0.05)
      decrease (64%) in cholesterol 7 alpha-hydroxylase-specific activity, mass (72%),
      steady-state mRNA levels (74%), and transcriptional activity (57%) as compared to
      CBD controls. Cholesterol feeding increased cholesterol 7 alpha-hydroxylase
      specific activity (288%), poly(A) RNA levels (291%), and transcriptional activity
      (220%) as compared to control animals. These results provide convincing evidence
      that bile salts, either directly or indirectly, down-regulate in vivo
      transcription of the cholesterol 7 alpha-hydroxylase gene, which is probably the
      major mechanism regulating the levels of this enzyme. The results of this study
      also suggest that the promoter for cholesterol 7 alpha-hydroxylase may have both
      bile salt- and sterol-responsive elements.

PMID- 1995605
TI  - NMR relaxation properties of 77Se-labeled proteins.
AB  - A 77Se-containing moiety has been attached to cysteine residues in bovine
      hemoglobin, reduced ribonuclease A, and glutathione by reaction with [77Se]6,6'
      diselenobis(3-nitrobenzoic acid). The resultant species contain Se-S linkages
      that have 77Se NMR absorptions in the range range of 568-580 ppm. Spectra have
      been recorded at 4.7 and 9.7 tesla (T). For labeled hemoglobin a line width of
      250 Hz is seen at 4.7 T and 1000 Hz at 9.4 T. This quadrupling of line width with
      doubling of observational field strength is consistent with exclusive relaxation
      by the chemical shift anisotropy (CSA) mechanism. These line widths are greater
      than expected for a molecule the size of hemoglobin and indicate some aggregation
      at the high concentrations used. Upon dissociation and partial unfolding of the
      hemoglobin subunits, the line widths of the selenium resonance decrease to 35 and
      120 Hz at 4.7 and 9.4 T, respectively. The spin-lattice relaxation time (T1) for
      the dissociated hemoglobin at 9.4 T was found to be 220 ms. Together with a value
      of 377 ms for the spin-spin relaxation time (T2), determined from the line width,
      an estimate of the CSA was made. This gave a value of 890 ppm, which is in accord
      with other values for Se(II) linked only by single bonds. When this value for the
      CSA is used, together with the CSA contribution to the line width, in estimating
      a correlation time for seleno(3-nitrobenzoic acid) (SeNB)-labeled glutathione, a
      value of 4 x 10(-11) s is obtained. For SeNB-labeled denatured ribonuclease, four
      distinct resonances are resolvable at 4.7 T and five resonances at 9.4 T. From T1
      values for these resonances and the value of 890 ppm for the CSA, an appropriate
      correlation time of 0.1 ns was determined, which should result in 77Se resonances
      of 0.2-1.0 Hz at 4.7 and 9.4 T, respectively. Much greater apparent line widths
      are observed, which are attributed to microheterogeneity resulting from formation
      of inter- and intramolecular disulfide linkages. It is concluded that when there
      are no complications from protein aggregation or chemical exchange, the CSA
      values anticipated to exist in glutathione peroxidase or other selenoproteins
      should result in resonances with line widths in the range from 27 to 170 Hz,
      depending on field strength. These resonances should therefore be observable in
      the intact protein, if 77Se-enriched material is available.

PMID- 1995607
TI  - Glucose-dependent and -independent effect of insulin on gene expression.
AB  - Insulin action on gene expression can be glucose-dependent or -independent.
      Accumulation of aldolase B mRNA and of an unidentified 5.4-kilobase mRNA as well
      as accumulation of L-type pyruvate kinase mRNAs (Decaux, J.F., Antoine, B., and
      Kahn, A. (1989) J. Biol. Chem. 264, 11584-11590) in cultured hepatocytes isolated
      from fasted rats require the presence of both glucose and insulin, these agents
      not being effective individually. In contrast, maintaining the amount of albumin
      and transferrin mRNAs in these hepatocytes requires the presence of insulin
      alone, glucose having no effect by itself. Transcription of the albumin gene,
      investigated by run-on assay, is active in the presence of insulin alone, with or
      without glucose, whereas transcription of the aldolase B gene is stimulated by
      glucose and insulin together, but not by insulin or glucose alone. In addition,
      the stability of the albumin and aldolase B mRNAs in cultured hepatocytes is
      lowered in the absence of glucose and insulin together as compared to the
      stability in the presence of one or both agents. These results confirm that
      transduction of the insulin signal occurs via distinct pathways; one of these
      pathways could involve a secondary insulin-dependent modification of metabolite
      concentration, whereas other pathways could be more directly related to the
      activity(ies) of the occupied insulin receptor.

PMID- 1995606
TI  - Restoration of the calcium binding activity of mutant calmodulins toward normal
      by the presence of a calmodulin binding structure.
AB  - The altered calcium binding activity of calmodulins (CaM) with point mutations
      can be restored toward that of wild type CaMs by the formation of a complex
      between CaM and a CaM binding sequence. Three different site-specific mutations
      resulted in selective effects on the apparent stoichiometry and affinity of CaM
      for calcium, with maintenance of the ability to activate myosin light chain
      kinase. The effects on calcium binding, however, were suppressed when the mutant
      CaMs were complexed with RS20, a peptide analog of a myosin light chain kinase
      CaM binding site. The mutations included: 1) a Glu----Ala mutation at two
      phylogenetically conserved calcium ligands in the second (E67A-CaM) and fourth
      (E140A-CaM) sites; and 2) a Ser----Phe mutation at residue 101 (S101F-CaM) which
      affects ion channel regulation. The mutant CaMs bind 4 calciums in the absence of
      magnesium, but two sites have approximately 60- to 300-fold weaker binding than
      wild-type CaM (SYNCAM CaM). E67A-CaM and E140A-CaM bound only two calciums and
      S101F-CaM bound 4 calciums in the presence of magnesium. E67A-CaM and E140A-CaM
      recovered the ability to bind 4 calcium ions in the presence of the RS20 CaM
      binding peptide. These results are consistent with models in which the calcium
      binding activity of CaM within a supramolecular complex is different from
      purified CaM and raise the possibility that the selective functional effects of
      in vivo mutations in the calcium binding sites of CaM might be partially due to
      the ability of some CaM binding proteins to select and utilize CaM conformations
      with calcium ligation structures different from the so-called canonical EF-hand.

PMID- 1995608
TI  - Interaction of androgen response elements with the DNA-binding domain of the rat
      androgen receptor expressed in Escherichia coli.
AB  - A fragment of the rat androgen receptor (amino acids 533-637) containing the DNA
      binding domain was produced in Escherichia coli as a fusion product with protein
      A of Staphylococcus aureus. The fusion protein was purified on IgG-Sepharose, a
      method that does not involve the use of denaturing agents. Approximately 4 mg of
      fusion protein was obtained from 500 ml of bacterial culture. In gel shift
      assays, the recombinant DNA-binding domain displays an affinity for a fragment of
      the long terminal repeat of mouse mammary tumor virus and for an intronic
      fragment of the gene coding for the C3 component of the androgen-regulated rat
      prostatic binding protein. In a DNase I footprinting assay, the fusion protein
      protects a sequence in the C3 fragment that has previously been shown to act as a
      functional androgen response element. Interestingly, a single base pair mutation
      in the response element, which abolishes androgen inducibility, also destroys the
      ability to interact with the recombinant androgen receptor DNA-binding domain.

PMID- 1995609
TI  - Extracellular ATP causes Ca2(+)-dependent and -independent insulin secretion in
      RINm5F cells. Phospholipase C mediates Ca2+ mobilization but not Ca2+ influx and
      membrane depolarization.
AB  - The mechanism by which extracellular ATP stimulates insulin secretion was
      investigated in RINm5F cells. ATP depolarized the cells as demonstrated both by
      using the patch-clamp technique and a fluorescent probe. The depolarization is
      due to closure of ATP-sensitive K+ channels as shown directly in outside-out
      membrane patches. ATP also raised cytosolic Ca2+ [( Ca2+]i). At the single cell
      level the latency of the [Ca2+]i response was inversely related to ATP
      concentration. The [Ca2+]i rise is due both to inositol trisphosphate mediated
      Ca2+ mobilization and to Ca2+ influx. The former component, as well as inositol
      trisphosphate generation, were inhibited by phorbol myristate acetate which
      uncouples agonist receptors from phospholipase C. This manoeuvre did not block
      Ca2+ influx or membrane depolarization. Diazoxide, which opens ATP-sensitive K+
      channels, attenuated membrane depolarization and part of the Ca2+ influx
      stimulated by ATP. However, the main Ca2+ influx component was unaffected by L
      type channel blockers, suggesting the activation of other Ca2+ conductance
      pathways. ATP increased the rate of insulin secretion by more than 12-fold but
      the effect was transient. Prolonged exposure to EGTA dissociated the [Ca2+]i rise
      from ATP-induced insulin secretion, since the former was abolished and the latter
      only decreased by about 60%. In contrast, vasopressin-evoked insulin secretion
      was more sensitive to Ca2+ removal than the accompanying [Ca2+]i rise. Inhibition
      of phospholipase C stimulation by phorbol myristate acetate abrogated vasopressin
      but only reduced ATP-induced insulin secretion by 34%. These results suggest that
      ATP stimulates insulin release by both phospholipase C dependent and distinct
      mechanisms. The Ca2+)-independent component of insulin secretion points to a
      direct triggering of exocytosis by ATP.

PMID- 1995610
TI  - Formation of Z,E,E-geranylgeranyl diphosphate by rat liver microsomes.
AB  - Rat liver microsomes catalyzed the formation of A,E,E-geranylgeranyl diphosphate
      from farnesyl diphosphate and isopentenyl diphosphate in the presence of Triton X
      100. Studies on product specificity using various primers such as Z,E-farnesyl
      diphosphate, E,E-farnesyl diphosphate, Z,E,E-geranylgeranyl diphosphate, E,E,E
      geranylgeranyl diphosphate, Z,E,E,E-geranylfarnesyl diphosphate, and E,E,E,E
      geranylfarnesyl diphosphate suggested that the microsomal dehydrodolichyl
      diphosphate synthase has such properties that it releases Z,E,E-geranylgeranyl
      diphosphate, the first intermediate, in the reactions with farnesyl diphosphate
      as the starting primer. Metabolic labeling of rat liver slices with [2
      3H]mevalonic acid revealed the accumulation of E,E,E-geranylgeranyl
      (di)phosphates as well as dolichyl (di)phosphate (C85 and C90) and
      dehydrodolichol (C85 and C90), but no accumulation of Z,E,E-geranylgeranyl
      (di)phosphate or E,E-farnesyl (di)phosphate was detected. Microsomal enzyme
      preparations from mouse liver and hamster liver also produced Z,E,E
      geranylgeranyl diphosphate from farnesyl diphosphate and isopentenyl diphosphate.

PMID- 1995611
TI  - Variable product specificity of microsomal dehydrodolichyl diphosphate synthase
      from rat liver.
AB  - Several detergents activated microsomal dehydrodolichyl diphosphate synthase of
      rat liver, but the chain length of products shifted downward from C90 and C95
      with increasing concentration of the detergents. Maximum activation was observed
      at the concentration of 2% Triton X-100, 30 mM octyl glucoside, 30 mM 3-[(3
      cholamidopropyl)dimethylammonio]-1-propanesulfonate, and 10 mM deoxycholate with
      the product chain length being C80-C85, C65-C75, C70-C75, and C55-C65,
      respectively. The activity of Triton X-100 solubilized enzyme was decreased by
      asolectin, phosphatidylethanolamine, and phosphatidylcholine. The chain lengths
      of products formed in the presence of these phospholipids were C85 and C90. In
      the presence of both phosphatidylcholine and Mg2+ the solubilized enzyme was able
      to produce C90 and C95 dehydrodolichyl diphosphates like native microsomal
      enzyme. Microsomal enzyme preparations from rat liver, brain, and testis
      catalyzed the formation of dehydrodolichyl diphosphates with the same chain
      lengths as those of the natural dolichols occurring in individual tissues. The
      chain length distribution of dehydrodolichyl products by (rat liver) microsomes
      also depended on the concentration of substrates. Not only did increasing the
      concentration of isopentenyl diphosphate lead to longer chain product, but
      decreasing that of farnesyl diphosphate increased product chain length.

PMID- 1995612
TI  - Localization of the 90-kDa heat shock protein-binding site within the hormone
      binding domain of the glucocorticoid receptor by peptide competition.
AB  - In this work, we used two approaches to localize the 90-kDa heat shock protein
      (hsp90)-binding site within the hormone-binding domain of the glucocorticoid
      receptor. In the first approach, derivatives of the glucocorticoid receptor
      deleted for increasing portions of the COOH terminus were translated in rabbit
      reticulocyte lysate, and the [35S]methionine-labeled translation products were
      immunoadsorbed with the 8D3 monoclonal antibody against hsp90. The data suggest
      that a segment from amino acids 604 to 659 (mouse) of the receptor is required
      for hsp90 binding. We have recently shown that the internal deletion mutant of
      the mouse receptor (delta 574-632) binds hsp90, although the complex is somewhat
      unstable (Housley, P. R., Sanchez, E. R., Danielsen, M., Ringold, G. M., and
      Pratt, W. B. (1990) J. Biol. Chem. 265, 12778-12781). The two observations
      indicate that amino acids 574-659 are involved in forming a stable receptor-hsp90
      complex and that region 632-659 is especially important. To test this hypothesis
      directly, we synthesized three peptides corresponding to segments in region 624
      665 and three peptides spanning the highly conserved sequence at amino acids 582
      617, and we then tested the ability of the peptides to compete for the
      association of hsp90 with the L cell glucocorticoid receptor. In this assay, the
      immunopurified hsp90-free mouse receptor is incubated with rabbit reticulocyte
      lysate, which directs the association of rabbit hsp90 with the mouse receptor,
      simultaneously converting the receptor to the steroid binding state. All three
      peptides spanning region 624-665 and a peptide corresponding to segment 587-606
      inhibited both hsp90 association with the receptor and reconstitution of steroid
      binding capacity. The data from all of the approaches support a two-site model
      for the hsp90-binding site in which the critical contact site occurs in region
      632-659, which contains a short proline-containing hydrophobic segment and
      adjacent dipole-plus-cysteine motif that are conserved among all of the hsp90
      binding receptors in the superfamily. A second hsp90 contact site is predicted in
      region 574-632, which contains the only highly conserved amino acid sequence in
      the receptor superfamily outside of the DNA-binding domain.

PMID- 1995613
TI  - Dog serum amyloid A protein. Identification of multiple isoforms defined by cDNA
      and protein analyses.
AB  - Five distinct serum amyloid A (SAA) cDNA clones have been isolated from a library
      constructed using hepatic mRNA isolated from an individual beagle dog with canine
      pain syndrome. This implies the existence of at least three SAA genes in the dog
      genome. One clone predicts a truncated "amyloid A-like" SAA molecule and offers a
      possible alternative mechanism for the pathogenesis of secondary amyloidosis.
      Relative to the human and mouse SAA proteins, an additional peptide of eight
      amino acids is specified by each of the dog cDNA clones. The existence of this
      peptide in all acute phase dog SAA proteins was confirmed by polyacrylamide gel
      electrophoresis in the presence of sodium dodecyl sulfate of acute phase high
      density lipoprotein and provides supporting evidence for gene conversion as a
      mechanism for maintaining the homogeneity of the SAA gene family within a
      species. Analysis of hepatic RNA following induction of an acute phase response
      shows a dramatic increase in SAA mRNA concentration; the SAA transcripts show a
      transient increase in size early in inflammation due to an increase in
      polyadenylation.

PMID- 1995614
TI  - Inhibition of human seminal fluid and Leishmania donovani phosphatases by
      molybdate heteropolyanions.
AB  - Inhibition of a tartrate-resistant acid phosphatase (ACP) from Leishmania
      donovani and the tartrate-sensitive ACP from human seminal fluid (prostatic ACP)
      was examined using a series of 13 molybdate-containing heteropolyanions. The
      heteropolyanions were divided into four groups based on the number of molybdenum
      atoms they contain: Group I, Mo4; Group II, Mo6-8; Group III, Mo12; Group IV,
      Mo18. Two of the four groups, those consisting of compounds that contain either
      an Mo4 unit or an Mo18 unit with a heteroatom in the central cavity, were potent
      inhibitors and exhibited the highest degree of selectivity against the
      leishmanial and seminal fluid ACPs. The inhibition of prostatic ACP by complex E2
      could be completely reversed by dialysis. Little inhibition of the acid
      phosphatase, beta-glucuronidase, or alpha-mannosidase from human spleen was
      observed with complexes B' and E2. For the seminal fluid phosphatase, the Ki
      values obtained with arsenate and vanadate depended markedly on pH, suggesting
      that, unlike most other phosphatases, the conformation of the inhibitor binding
      site on human seminal fluid ACP is pH-dependent. Results of competition
      experiments performed with various inhibitor pairs indicated that complex D2
      binds to the active site of prostatic ACP while complex M binds at some site on
      the enzyme that affects the active site. Binding of complex M also modifies the
      affinity of the enzyme for other inhibitors such as vanadate. The potency of
      several heteropolyanion complexes and their selective inhibition of
      pathophysiologically significant acid phosphatases indicate that these compounds
      may have value as tools for study of the structure and function of this class of
      enzyme and perhaps in the therapy of human disease.

PMID- 1995616
TI  - Purification and characterization of GDP-L-Fuc-N-acetyl-beta-D-glucosaminide
      alpha 1----3fucosyltransferase from human neuroblastoma cells. Unusual substrate
      specificities of the tumor enzyme.
AB  - Fucosyl residues in the alpha 1----3 linkage to N-acetylglucosamine (Fuc alpha 1-
      --3GlcNAc) on oligosaccharides of glycoproteins and glycolipids have been
      detected in certain human tumors and are developmentally expressed (reviewed in
      Foster, C. S., and Glick, M. C. (1988) Adv. Neuroblastoma Res. 2, 421-432). In
      order to understand control mechanisms for the biosynthesis of these fucosylated
      glycoconjugates, GDP-L-Fuc-N-acetyl-beta-D-glucosaminide alpha 1---
      3fucosyltransferase was purified from human neuroblastoma cells, CHP 134,
      utilizing either the immobilized oligosaccharide or disaccharide substrates. The
      enzyme, extracted from CHP 134 cells, was purified by DEAE- and SP-Sephadex
      chromatography and then by either immobilized substrate. alpha 1---
      3Fucosyltransferase was obtained in approximately 10% yield and was purified
      45,000-fold from the cell extract. The kinetic properties of the enzyme showed an
      apparent KGDP-Fuc 43 microM, KGal beta 1----4GlcNAc 0.4 mM, KGal beta 1----4Glc
      8.1 mM, and KFuc alpha 1----2Gal beta 1----4Glc 1.0 mM. Polyacrylamide gel
      electrophoresis of the affinity-purified enzyme showed two proteins which
      migrated, Mr = 45,000-40,000. The enzyme differed in substrate specificity, pH
      optimum, response to N-ethylmaleimide and ion requirements from the enzymes
      purified from human milk or serum. The inability of alpha 1---
      3fucosyltransferase to transfer to substrates containing NeuAc alpha 2----3 or
      alpha 2----6Gal is in contrast to the reports for the enzyme in other human
      tumors. This substrate specificity correlates with the oligosaccharide residues
      thus far defined on glycoproteins of CHP 134 cells since NeuAc and Fuc alpha 1---
      3GlcNAc have yet to be detected on the same oligosaccharide antenna. However, the
      enzyme transfers to Fuc alpha 1----2Gal beta 1----4GlcNAc/Glc with higher
      activity than the unfucosylated disaccharides, although neither alpha 1---
      2fucosyltransferase nor Fuc alpha 1----2 residues have been detected in CHP 134
      cells. The different substrate specificities of alpha 1----3fucosyltransferase
      isolated from human tumors and normal sources leads to the suggestion that a
      family of alpha 1----3fucosyltransferases may exist and that they may be
      differentially expressed in human tumors.

PMID- 1995615
TI  - Biosynthesis and secretion of an osteopontin-related 20-kDa polypeptide in the
      Madin-Darby canine kidney cell line.
AB  - We describe a 20-kDa phosphorylated polypeptide, which is secreted constitutively
      at the apical surface of the kidney-derived Madin-Darby canine kidney cell line.
      Using polyclonal antibodies raised against this protein, we show that it is
      generated from a 60-kDa O-glycosylated, sulfated, and phosphorylated precursor
      protein by an intracellular proteolytic maturation step, which is pH-sensitive.
      Amino acid sequence analysis of the 20-kDa secreted polypeptide demonstrated that
      it displays 70% identity with the carboxyl-terminal amino acids of human
      osteopontin. The amino-terminal amino acid of the 20-kDa polypeptide corresponds
      to amino acid 213 of human osteopontin. Thrombin has been shown to cleave rat
      osteopontin in vivo and in vitro at amino acid 153, yielding two fragments of 28
      and 26 kDa. A similar cleavage product can be detected by thrombin treatment of
      the 60-kDa precursor, suggesting that the precursor is identical or closely
      related to osteopontin. In the rat nephron, the protein has been localized along
      the luminal surfaces of the proximal and distal tubule and the collecting duct
      cells. These results show that in the kidney-derived cell line Madin-Darby canine
      kidney osteopontin or a closely related protein is proteolytically processed to a
      20-kDa polypeptide, raising the possibility that diverse functions of osteopontin
      in various tissues might be attributed to specific processing to distinct
      polypeptides.

PMID- 1995617
TI  - Secretagogue-coupled changes in the expression of glutamine/glutamic acid-rich
      proteins (GRPs). Isoproterenol induces changes in GRP transcript expression and
      changes in isoforms secreted.
AB  - Glutamine/glutamic-acid rich proteins (GRPs) are a family of rat submandibular
      gland acinar proteins which are secreted in response to beta-adrenergic agonists
      such as isoproterenol. Two forms of GRP transcripts have been identified by
      isolating plasmids containing cDNAs which code for two distinct GRPs, termed GRP
      Ca and GRP-Cb. GRP-Ca and GRP-Cb have identical sequences up to nucleotide 670.
      This is followed by a unique 90- (GRP-Ca) or 95- (GRP-Cb) base pair element. Both
      forms have common 3' nucleotide sequences, although the GRP-Cb stop codon is 27
      base pairs further 3' from the start site of transcription. Systemic exposure to
      isoproterenol results in a decrease in the relative steady-state level of GRP-Ca
      transcripts within 24 h, whereas GRP-Cb message increases after several days of
      isoproterenol treatment. The demonstration that secretagogues such as
      isoproterenol can modulate changes in salivary protein expression suggests that
      the machinery responsible for exocytosis is functionally coupled to the cellular
      apparatus involved in acinar protein production.

PMID- 1995618
TI  - Reductive activation of the coenzyme A/acetyl-CoA isotopic exchange reaction
      catalyzed by carbon monoxide dehydrogenase from Clostridium thermoaceticum and
      its inhibition by nitrous oxide and carbon monoxide.
AB  - The final steps in the synthesis of acetyl-CoA by CO dehydrogenase (CODH) have
      been studied by following the exchange reaction between CoA and the CoA moiety of
      acetyl-CoA. This reaction had been studied earlier (Pezacka, E., and Wood, H. G.
      (1986) J. Biol. Chem. 261, 1609-1615 and Ramer, W. E., Raybuck, S. A., Orme
      Johnson, W. H., and Walsh, C. T. (1989) Biochemistry 28, 4675-4680). The
      CoA/acetyl-CoA exchange activity was determined at various controlled redox
      potentials and was found to be activated by a one-electron reduction with half
      maximum activity occurring at -486 mV. There is approximately 2000-fold
      stimulation of the exchange by performing the reaction at -575 mV relative to the
      rate at -80 mV. Binding of CoA to CODH is not sensitive to the redox potential;
      therefore, the reductive activation affects some step other than
      association/dissociation of CoA. We propose that a metal center on CODH with a
      midpoint reduction potential of less than or equal to -486 mV is activated by a
      one-electron reduction to cleave the carbonyl-sulfur bond and/or bind the acetyl
      group of acetyl-CoA. Based on a comparison of the redox dependence of this
      reaction with that for methylation of CODH (Lu, W-P., Harder, S. R., and
      Ragsdale, S. W. (1990) J. Biol. Chem. 265, 3124-3133) and CO2 reduction and
      formation of the Ni-Fe-C EPR signal (Lindahl, P. A., Munck, E., and Ragsdale, S.
      W. (1990) J. Biol. Chem. 265, 3873-3879), we propose that the assembly of the
      acetyl group of acetyl-CoA, i.e. binding the methyl group of the methylated
      corrinoid/iron-sulfur protein, binding CO, and methyl migration to form the
      acetyl-CODH intermediate, occur at the novel Ni-Fe3-4-containing site in CODH. CO
      has two effects on the CoA/acetyl-CoA exchange: it activates the reaction due to
      its reductive capacity and its acts as a noncompetitive inhibitor. We also
      discovered that the CoA/acetyl-CoA exchange was inhibited by nitrous oxide via an
      oxidative mechanism. In the presence of a low-potential electron donor, CODH
      becomes a nitrous oxide reductase which catalytically converts N2O to N2. This
      study combined with earlier results (Lu, W-P., Harder, S. R., and Ragsdale, S. W.
      (1990) J. Biol. Chem. 265, 3124-3133) establishes that the two-subunit form of
      CODH is completely active in all reactions known to be catalyzed by CODH.

PMID- 1995619
TI  - Phosphatidate phosphatase from Saccharomyces cerevisiae. Isolation of 45- and 104
      kDa forms of the enzyme that are differentially regulated by inositol.
AB  - Immunoblot analysis of cell extracts using antibodies specific for the 91-kDa
      form of membrane-associated phosphatidate phosphatase from Saccharomyces
      cerevisiae (Lin, Y.-P., and Carman, G.M. (1989) J. Biol. Chem. 264, 8641-8645)
      revealed the existence of a 45-kDa form of the enzyme. Immunoblot analysis also
      showed that the 91-kDa form of the enzyme was a proteolytic product of a 104-kDa
      enzyme. The mitochondrial fraction contained the 45-kDa enzyme, whereas the
      microsomal fraction contained the 45- and 104-kDa enzymes. In vivo labeling
      experiments showed that the 104-kDa form of phosphatidate phosphatase was not a
      precursor of the 45-kDa form of the enzyme. The 45- and 104-kDa forms of
      phosphatidate phosphatase were purified and characterized. The enzymological
      properties of both enzymes were similar. However, the phosphatidate phosphatase
      45- and 104-kDa proteins differed with respect to their isoelectric points and
      peptide fragments resulting from V8 proteolysis and cyanogen bromide cleavage.
      The expression of the phosphatidate phosphatase 45- and 104-kDa enzymes were
      regulated differentially in cells supplemented with inositol. The addition of
      inositol to the growth medium resulted in the induction of the phosphatidate
      phosphatase 45-kDa enzyme. The expression of the 104-kDa enzyme was not affected
      by inositol. Both forms of phosphatidate phosphatase were induced when cells
      entered the stationary phase of growth.

PMID- 1995620
TI  - Effect of eukaryotic initiation factor 4F on AUG selection in a bicistronic mRNA.
AB  - Artificial bicistronic mRNAs based on rabbit beta-globin and bacterial
      chloramphenicol acetyltransferase protein-coding sequences were tested for
      translation activity in a mouse astrocytoma cell-free extract. This cell extract
      exhibited an apparent preference for 5'-distal or internal initiation over 5'
      proximal ("first AUG") initiation. 5'-Distal initiation appeared to be 5'-cap
      independent, suggesting that nonstandard initiation was responsible. This
      conclusion was based on a lack of inhibition of internal initiation by added cap
      analog and insensitivity of internal initiation to the presence or absence of a
      5'-cap structure. Exogenous reticulocyte initiation factors were tested for
      effect on 5'-proximal initiation. The only factor with a significant effect was
      found to be eukaryotic initiation factor 4F, or the cap-binding protein. Addition
      of this factor promoted 5'-end initiation as evident by a general increase in 5'
      proximal open reading frame (ORF) product relative to 5'-distal ORF product. The
      relative expression of 5'-proximal to 5'-distal ORFs in bicistronic or
      multicistronic mRNAs may very well be dependent on activity levels of eukaryotic
      initiation factor 4F and possibly other mRNA-dependent initiation factors.

PMID- 1995621
TI  - Fluorine nuclear magnetic resonance analysis of the ligand binding properties of
      two homologous rat cellular retinol-binding proteins expressed in Escherichia
      coli.
AB  - Comparative 19F NMR studies were performed on rat cellular retinol-binding
      protein (CRBP) and cellular retinol-binding protein II (CRBPII) to better
      understand their role in intracellular retinol metabolism within the polarized
      absorptive epithelial cells (enterocytes) of the intestine. Efficient
      incorporation of 6-fluorotryptophan (6-FTrp) into these homologous proteins was
      achieved by growing a tryptophan auxotroph of Escherichia coli, harboring
      prokaryotic expression vectors with either a full-length rat CRBPII or CRBP cDNA
      on defined medium supplemented with the analog. It is possible to easily
      distinguish resonances corresponding to 6-FTrp-apoCRBP, 6-FTrp-CRBP-retinol (or
      retinal), 6-FTrp-apoCRBPII, and 6-FTrp-CRBPII-retinol (or retinal). We were thus
      able to use 19F NMR spectroscopy to monitor transfer of all-trans-retinol and all
      trans-retinal between CRBPII and CRBP in vitro. Retinol complexed to CRBPII is
      readily transferred to CRBP, whereas retinol complexed to CRBP is not readily
      transferred to CRBPII. We estimated that the Kd for CRBP-retinol is approximately
      100-fold less than the Kd for CRBPII-retinol. Transfer of all-trans-retinal
      occurs readily from CRBPII to CRBP and from CRBP to CRBPII. Results from
      competitive binding studies with retinol and retinal indicated that there is a
      much larger difference between the affinities of CRBP for retinol and retinal
      than between the affinities of CRBPII for these two ligands. However, the
      differences in binding specificities reflect differences in how the two proteins
      interact with retinol, rather than with retinal. 19F NMR analysis of recombinant
      isotopically labeled proteins represents a sensitive new and useful method for
      monitoring retinoid flux between the CRBPs in vitro.

PMID- 1995622
TI  - Lignin peroxidase: toward a clarification of its role in vivo.
AB  - The extracellular lignin peroxidase from the white-rot basidiomycete
      Phanerochaete chrysosporium is thought to play an important role in lignin
      biodegradation. However, the majority of lignin-derived preparations actually
      experience overall polymerization at the hands of the enzyme in vitro. It has now
      been found that, in the presence of H2O2 at pH 4.0, the monomeric lignin
      precursor coniferyl alcohol is polymerized quantitatively by a lignin peroxidase
      preparation which is uncontaminated with MnII-dependent peroxidases. 13C NMR
      spectrometry of the resulting dehydropolymerisates from 13C-labeled monolignols
      confirms that the frequencies of different interunit linkages are very similar to
      those engendered through the action of horseradish peroxidase with H2O2. Indeed,
      lignin peroxidase does not ultimately seem to be a prerequisite for lignin
      degradation in vivo, yet its activity can still accelerate the conversion of
      lignin-derived preparations by P. chrysosporium to CO2. Consequently, lignin
      peroxidase can provisionally be expected to fulfill two important functions. On
      the one hand, the enzyme may detoxify lower molecular weight phenolic compounds
      released from lignins during their fungal decomposition. On the other hand,
      through the introduction of suitable functional groups, lignin peroxidase could
      indirectly enhance the susceptibility of macromolecular lignin structures toward
      depolymerization by another enzyme.

PMID- 1995623
TI  - Lymphocyte activation and phospholipid pathways. 31P magnetic resonance studies.
AB  - 31P NMR spectra of perfused lymphocytes, embedded in alginate capsules and
      activated by interleukin-2, were remarkably different from those of control
      lymphocytes. The main differences were the appearance and gradual increase in
      phosphodiester signals, glycerophosphocholine and glycerophosphoethanolamine.
      These metabolic changes also occurred following perfusion with phorbol ester and
      after incubation with phytohemagglutinin (PHA) and were not dependent on a
      special growth medium. Nifedipine, a calcium channel blocking drug, inhibited the
      effects of phytohemagglutinin, but not of interleukin-2. There were no NMR
      spectral differences between peripheral lymphocytes, stimulated for 3 weeks, and
      tumor-infiltrating lymphocytes. Thus, sustained accelerated turnover of
      phosphatidylcholine and phosphatidylethanolamine is an inherent feature of the
      activation process. 31P NMR spectra of lymphocytes are characterized by a low
      signal of phosphocholine. Perfusion studies with high concentrations of choline
      and the use of dapsone, an inhibitor of cytidylyltransferase, indicated that
      choline kinase plays a key role in regulating phosphaditylcholine synthesis in
      human lymphocytes.

PMID- 1995624
TI  - Biochemical characterization of 39-kDa class I histocompatibility antigen in
      plasma. A secretable membrane protein derived from transmembrane domain deletion.
AB  - Three human class I major histocompatibility antigens (HLA) with molecular masses
      of 44, 39, and 36 kDa were identified in plasma by immunoprecipitation and
      immunoblotting. Further biochemical characterization showed that these antigens
      in plasma could be fractionated by Sephacryl S-300 column chromatography into two
      different pools. The 44-kDa intact HLA heavy chains are detected only in pool I
      and have an apparent molecular weight of 200,000 as determined by calibrated gel
      filtration column chromatography. The 39- and 36-kDa HLA heavy chains are present
      only in pool II and have an apparent molecular weight of 50,000. HLA in pool I
      can be extracted by Triton X-114 detergent, but 39- and 36-kDa plasma HLA in pool
      II are water soluble and not extractable by Triton X-114. Amino acid sequences of
      NH2 termini for 44- and 39-kDa plasma HLA are identical to that of cellular HLA.
      In contrast, the NH2-terminal amino acid sequence for 36-kDa plasma HLA has not
      been reported previously for any other proteins. Since the loss of both
      transmembrane domain and cytoplasmic tail at the carboxyl terminus of HLA will
      generate a 36-kDa protein, the findings suggest that the 39-kDa HLA might be the
      product of alternatively spliced mRNA with deletion of the exon coding for
      transmembrane domain. By using polymerase chain reaction and DNA sequencing, the
      presence of alternatively spliced mRNA with deletion of the transmembrane domain
      exon was identified in mononuclear leukocytes of peripheral blood. This
      alternatively spliced HLA mRNA was not detectable in mononuclear leukocytes of an
      individual who had no 39-kDa plasma HLA. This finding indicates that the
      alternatively spliced mRNA in mononuclear leukocytes is responsible for the
      synthesis of a secretable class I HLA.

PMID- 1995625
TI  - Role of acidic residues as substrate determinants for casein kinase I.
AB  - Sites phosphorylated by casein kinase I have been characterized by the presence
      of acidic amino acids NH2-terminal to the modified residue. Recently,
      phosphoserine was shown to be a particularly effective determinant for casein
      kinase I action when present in the motif -S(P)-X-X-S- (Flotow, H., Graves, P.
      R., Wang, A., Fiol, C. J., Roeske, R. W., and Roach, P. J. (1990) J. Biol. Chem.
      265, 14264-14269). Nonetheless, nonphosphorylated substrates for casein kinase I
      are well documented. In this study, we examined the efficacy of Asp and Glu
      residues as determinants of casein kinase I action using synthetic peptide
      substrates. Peptides with runs of Asp residues in the motif Dn-X-X-S- were
      substrates for casein kinase I. Peptides with n = 3 or 4 were the most effective
      substrates, much better than n = 2. The peptide with n = 1, a single Asp residue,
      was a very poor substrate. A block of 4 Glu residues was a little less effective
      as a substrate determinant than 4 Asp residues in an otherwise identical peptide.
      The most effective substrate, with the motif -D-D-D-D-X-X-S-, was specific for
      casein kinase I and was not detectably phosphorylated by cyclic AMP-dependent
      protein kinase, casein kinase II, glycogen synthase kinase 3, or phosphorylase
      kinase and thus will be useful for the specific assay of casein kinase I. This
      peptide was nonetheless significantly worse as a substrate than peptides in which
      casein kinase I action was determined by phosphoserine in the -3 position. Still,
      the fact that Asp or Glu residues can specify a casein kinase I substrate
      suggests that acidic character has a role in substrate selection by this protein
      kinase.

PMID- 1995626
TI  - 1H and 119Sn magnetic resonance study of the SnIV protoporphyrin IX complex of
      equine myoglobin. Structure of the porphyrin-binding pocket.
AB  - Tin protoporphyrin IX (SnPP) is being used in the treatment of
      hyperbilirubinemia. We have studied the SnPP complex with equine myoglobin (EqMb)
      by 1H and 119Sn nuclear magnetic resonance spectroscopy (NMR) as a general model
      for SnPP interaction with hemoproteins. The complex formed from SnPP and EqMb,
      SnPP.EqMb, was found to have essentially the same porphyrin-binding pocket as
      EqMbCO, including the same porphyrin orientation in the major form of EqMbCO.
      119Sn NMR spectroscopy has been used to demonstrate that the proximal His93F8
      metal coordination is likely to be intact in SnPP.EqMb. Minor shifts in the side
      chain positions of some of the residues are indicated, possibly reflecting the
      presence of water in the sixth coordination site. SnPP.EqMb appears to be stable;
      it persists at room temperature for weeks and exhibits very slow exchange rates
      (2H for 1H) for a large number of amide protons in the pH range 7-9.

PMID- 1995627
TI  - Hormone-dependent androgen receptor phosphorylation is accompanied by receptor
      transformation in human lymph node carcinoma of the prostate cells.
AB  - Phosphorylation of the androgen receptor was investigated in the absence of
      hormone as well as during and after transformation of the receptor to the tight
      nuclear binding form. Human prostate tumor cells (LNCaP) were labeled for 4 h
      with [32P]orthophosphate in the presence or absence of steroid. Subsequently,
      androgen receptors were immunoprecipitated either from total cell lysates or from
      nuclear extracts using a specific monoclonal antibody. The immunoprecipitated
      receptor preparations were analyzed by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis, Western blotting, using a polyclonal antiserum, and
      autoradiography. It was observed that the androgen receptor is already
      phosphorylated in the absence of hormone, but undergoes a hormone-induced
      additional phosphorylation. After administration of 10 nM R1881, a 1.8-fold
      increase in phosphorylation over nonstimulated control cells was reached.
      Moreover, the amount of nuclear extractable androgen receptor was increased; the
      acquisition of tight nuclear binding capacity was accompanied by hormone-induced
      receptor phosphorylation.

PMID- 1995629
TI  - Heteroduplex repair in extracts of human HeLa cells.
AB  - A general repair process for DNA heteroduplexes has been detected in HeLa cell
      extracts. Using a variety of M13mp2 DNA substrates containing single-base
      mismatches and extra nucleotides, extensive repair is observed after incubation
      with HeLa cell cytoplasmic extracts and subsequent transfection of bacterial
      cells with the treated DNA. Most, but not all, mispairs as well as two frameshift
      heteroduplexes are repaired efficiently. Parallel measurements of repair in HeLa
      extracts and in Escherichia coli suggest that repair specificities are similar
      for the two systems. The presence of a nick in the molecule is required for
      efficient repair in HeLa cell extracts, and the strand containing the nick is the
      predominantly repaired strand. Mismatch-dependent DNA synthesis is observed when
      radiolabeled restriction fragments, produced by reaction of the extract with
      heteroduplex and homoduplex molecules, are compared. Specific labeling of
      fragments, representing a region of approximately 1,000 base pairs and containing
      the nick and the mismatch, is detected for the heteroduplex substrate but not the
      homoduplex. The repair reaction is complete after 20 min and requires added Mg2+,
      ATP, and an ATP-regenerating system, but not dNTPs, which are present at
      sufficient levels in the extract. An inhibitor of DNA polymerase beta,
      dideoxythimidine 5'-triphosphate, does not inhibit mismatch-specific DNA
      synthesis. Aphidicolin, an inhibitor of DNA polymerases alpha, delta, and
      epsilom, inhibits both semiconservative replication and repair synthesis in the
      extract. Butylphenyl-dGTP also inhibits both replicative and repair synthesis but
      at a concentration known to inhibit DNA polymerase alpha preferentially rather
      than delta or epsilon. This suggests that DNA polymerase alpha may function in
      mismatch repair.

PMID- 1995628
TI  - Mechanism of hydrogen peroxide formation catalyzed by NADPH oxidase in thyroid
      plasma membrane.
AB  - The thyroid plasma membrane contains a Ca2(+)-regulated NADPH-dependent H2O2
      generating system which provides H2O2 for the thyroid peroxidase-catalyzed
      biosynthesis of thyroid hormones. The plasma membrane fraction contains a Ca2(+)
      independent cytochrome c reductase activity which is not inhibited by superoxide
      dismutase. But it is not known whether H2O2 is produced directly from molecular
      oxygen (O2) or formed via dismutation of super-oxide anion (O2-). Indirect
      evidence from electron scavenger studies indicate that the H2O2 generating system
      does not liberate O2-, but studies using the modified peroxidase,
      diacetyldeuteroheme horseradish peroxidase, to detect O2- indicate that H2O2 is
      provided via the dismutation of O2-. The present results provide indirect
      evidence that the cytochrome c reductase activity is not a component of the NADPH
      dependent H2O2 generator, since it was removed by washing the plasma membranes
      with 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid without
      affecting H2O2 generation. Spectral studies with diacetyldeuteroheme-substituted
      horseradish peroxidase showed that the thyroid NADPH-dependent H2O2 generator
      does not catalyze superoxide anion formation. The O2- adduct compound (compound
      III) was formed but was completely inhibited by catalase, indicating that the
      initial product was H2O2. The rate of NADPH oxidation also increased in the
      presence of diacetylheme peroxidase. This increase was blocked by catalase and
      was greatly enhanced by superoxide dismutase. The O2- adduct compound (compound
      III) was produced in the presence of NADPH when glucose-glucose oxidase (which
      does not produce O2-) was used as the H2O2 generator. NADPH oxidation occurred
      simultaneously and was enhanced by superoxide dismutase. We conclude that O2-
      formation occurs in the presence of an H2O2 generator, diacetylheme peroxidase
      and NADPH, but that it is not the primary product of the H2O2 generator. We
      suggest that O2- formation results from oxidation of NADPH, catalyzed by the
      diacetylheme peroxidase compound I, producing NADP degree, which in turn reacts
      with O2 to give O2-.

PMID- 1995630
TI  - The 1-aminocyclopropane-1-carboxylate synthase of Cucurbita. Purification,
      properties, expression in Escherichia coli, and primary structure determination
      by DNA sequence analysis.
AB  - The key regulatory enzyme in the biosynthetic pathway of the plant hormone
      ethylene is 1-aminocyclopropane-1-carboxylic acid (ACC) synthase (EC 4.4.1.14).
      We have partially purified ACC synthase 6,000-fold from Cucurbita fruit tissue
      treated with indoleacetic acid + benzyladenine + aminooxyacetic acid + LiCl. The
      enzyme has a specific activity of 35,000 nmol/h/mg protein, a pH optimum of 9.5,
      an isoelectric point of 5.0, a Km of 17 microM with respect to S
      adenosylmethionine, and is a dimer of two identical subunits of approximately
      46,000 Da each. The subunit exists in vivo as a 55,000-Da species similar in size
      to the primary in vitro translation product. DNA sequence analysis of the cDNA
      clone pACC1 revealed that the coding region of the ACC synthase mRNA spans 493
      amino acids corresponding to a 55,779-Da polypeptide; and expression of the
      coding sequence (pACC1) in Escherichia coli as a COOH terminus hybrid of beta
      galactosidase or as a nonhybrid polypeptide catalyzed the conversion of S
      adenosylmethionine to ACC (Sato, T., and Theologis, A. (1989) Proc. Natl. Acad.
      Sci. U.S.A. 86, 6621-6625). Immunoblotting experiments herein show that the
      molecular mass of the beta-galactosidase hybrid polypeptide is 170,000 Da, and
      the size of the largest nonhybrid polypeptide is 53,000 Da. The data suggest that
      the enzyme is post-translationally processed during protein purification.

PMID- 1995631
TI  - cDNA cloning of a myosin heavy chain isoform in embryonic smooth muscle and its
      expression during vascular development and in arteriosclerosis.
AB  - Adult rabbit smooth muscles contain two types of myosin heavy chain (MHC)
      isoforms, SM1 and SM2 which are generated through alternative RNA splicing from a
      single gene (Nagai, R., Kuro-o, M., Babij, P. & Periasamy, M. (1989) J. Biol.
      Chem. 264, 9734-9737). We previously reported that the expression of SM1 and SM2
      during vascular development is differentially regulated at the level of RNA
      splicing, whereby SM1 is constitutively expressed from early development but SM2
      appear after birth (Kuro-o, M., Nagai, R., Tsuchimochi, H., Katoh, H., Yazaki,
      Y., Ohkubo, A. & Takaku, F. (1989) J. Biol. Chem. 264, 18272-18275). We also
      demonstrated that embryonic vascular smooth muscles contain a third type of MHC
      isoform, referred to as SMemb in this report, which comigrates on sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis with SM2. In the present study we have
      isolated and characterized a cDNA clone (FSMHC34) for SMemb. FSMHC34 encodes the
      light meromyosin region including the carboxyl terminus and showed 70% amino acid
      sequence identity with SM1 or SM2. SMemb is a nonmuscle-type MHC and identical
      with brain MHC, but clearly distinct from 196-kDa nonmuscle MHC in cultured
      smooth muscle cells. The expression of SMemb was predominant in embryonic and
      perinatal aortas, but down-regulated with vascular development. Interestingly
      SMemb was reexpressed in proliferating smooth muscle cells of arteriosclerotic
      neointimas. These results suggest that smooth muscle proliferation is coupled to
      the expression of SMemb and that dedifferentiation of smooth muscles toward the
      embryonic phenotype is involved in the mechanisms underlying atherosclerosis.

PMID- 1995632
TI  - Role of the proregion in the production and secretion of the Yarrowia lipolytica
      alkaline extracellular protease.
AB  - The yeast Yarrowia lipolytica secretes an alkaline extracellular protease (AEP).
      It is first synthesized as a precursor comprising a putative signal peptide, a
      stretch of 10 X-Ala or X-Pro sequences that are substrates for a dipeptidyl
      aminopeptidase, a large pro-region that contains a glycosylation site and two Lys
      Arg sites that can be cleaved by a KEX2-like endoprotease and finally the mature
      protease itself. A defect in the XPR6 (KEX2-like) gene results in the secretion
      of an inactive proenzyme (Matoba, S., and Ogrydziak, D. M. (1989) J. Biol. Chem.
      264, 6037-6043), showing that the proregion inhibits protease activity. To
      determine whether the proregion plays an additional role in protease secretion,
      we have generated deletions and point mutations in the corresponding region of
      the structural gene. In this paper we examine the effects of these mutations on
      AEP secretion and maturation and show that the proregion is essential for its
      secretion. All deletions affecting the proregion resulted in the intracellular
      accumulation of unprocessed precursors. Deletion of the glycosylation site in the
      proregion resulted in the production of an unglycosylated precursor that was
      secreted and matured correctly at 18 degrees C but accumulated in the cells at 28
      degrees C. From these results, we propose that the AEP prosequence plays an
      additional essential role in guiding the proper folding of the protein into a
      conformation compatible with secretion.

PMID- 1995633
TI  - Purification and characterization of novel heparan sulfate proteoglycans produced
      by murine erythroleukemia cells in the growing phase.
AB  - Murine erythroleukemia cells (Friend erythroleukemia cells of a C-10-6 line)
      synthesized sulfated glycosaminoglycans consisting mainly of heparan sulfate
      (more than 95%) with a small amount of chondroitin 4-sulfate. The heparan sulfate
      occurred as proteoglycans, of which the cell-associated component was separated
      into urea-insoluble (UI) and urea-soluble (US) fractions. The UI proteoglycan
      consisted of a single homogeneous molecular species with an estimated Mr of
      360,000 (C(UI)PG), whereas the US component was composed of two subfractions: a
      homogeneous species with an Mr of 280,000 (C(US)PGI) and a mixture of compounds
      with Mr values of less than 80,000 (C(US)PGII), which were isolated in yields of
      about 110, 340, and 80 micrograms of hexuronate (HexUA), respectively, from 1.37
      g of an acetone powder prepared from 5.7 x 10(9) cells in the logarithmic phase
      of growth. The proteoglycan released into the medium (12 liters) was a single
      homogeneous species with an Mr of 320,000 (MPG) which was purified in a yield of
      500 micrograms of hexuronate. The major, cell-associated proteoglycan, C(US)PGI,
      had very high contents of serine and glycine, accounting for approximately 80% of
      the total amino acids. This proteoglycan as well as the other two large
      proteoglycans, C(UI)PG and MPG, were highly resistant to degradation by various
      proteinases. These three proteoglycans, C(UI)PG, C(US)PGI, and MPG, had heparan
      sulfates with estimated Mr values of 32,000, 27,000, and 30,000. On the other
      hand, the Mr of the smaller proteoglycan, C(UI)PGII, was not significantly
      different before and after beta-elimination, indicating that it contains only a
      small peptide, if any. The heparan sulfate of this proteoglycan consisted of
      smaller and heterogeneous molecular species with Mr values of 26,000, 20,000, and
      4,000. Digestion of these heparan sulfates with heparitinase I plus II resulted
      in almost complete depolymerization and gave six unsaturated disaccharides, delta
      HexUA-GlcNAc, delta HexUA-Glc-NAc(6-SO4), delta HexUA-GlcNSO3, delta HexUA
      GlcNSO3 (6-SO4), delta HexUA(2-SO4)-GlcNSO3, and delta HexUA(2-SO4)-GlcNSO3(6
      SO4). The relative amounts of these disaccharides generated from the individual
      heparan sulfates showed that an average ratio of sulfate residues to repeating
      disaccharide units of the C(US)PGII-derived heparan sulfate (0.97) was
      significantly higher than those of the other three large proteoglycan-derived
      glycosaminoglycans (0.54-0.70).

PMID- 1995634
TI  - The interaction of monomeric actin with two binding sites on Acanthamoeba
      actobindin.
AB  - Actobindin was previously shown to be an 88-residue polypeptide (Mr 9761) with an
      internal tandem repeat of 33-34 amino acids. Sedimentation equilibrium
      experiments have confirmed this Mr for native actobindin. Pyreneglyoxal-labeled
      actobindin had a similar Mr by sedimentation equilibrium analysis and bound to
      actin in a manner qualitatively similar to unmodified actobindin as determined by
      gel electrophoretic analysis of covalently cross-linked products. The
      stoichiometry of the actin-actobindin interaction was determined from the change
      in apparent Mr of pyrene-glyoxal-labeled actobindin in the presence of actin, as
      determined by scanning the ultracentrifuge cell at a wavelength that detected
      only the labeled protein. These data were consistent with the formation of a
      complex containing two actin and one actobindin molecules. The overall KD
      describing the binding of the first actin to either of the two sites on
      actobindin was 3.3 microM. The binding constant for the second actin suggested
      either negative cooperativity or inequality of the two actin-binding sites.
      Similar binding constants were obtained by analysis of the fluorescence
      enhancement that occurred when actobindin bound to actin labeled with either
      pyrene iodoacetamide or 4-(N-iodoacetoxyethyl-N-methyl)-7-nitrobenz-2-oxa-1,3
      diazole. Cross-linking experiments with 1-ethyl-3-(3-dimethylaminopropyl)
      carbodiimide and N-hydroxy-sulfosuccinimide qualitatively agreed with predictions
      made from a two-binding site model. Additionally, both the fluorescence and cross
      linking experiments suggested that the interaction of the two actin molecules may
      contribute to the stability of the heterotrimeric complex.

PMID- 1995635
TI  - A human serine endopeptidase, purified with respect to activity against a peptide
      with phosphoserine in the P1' position, is apparently identical with prolyl
      endopeptidase.
AB  - The present work describes the detection, purification, and characterization of a
      serine endopeptidase with preference for a phosphoserine in the P1' position of
      the substrate. During probing for the enzyme in crude extracts, as well as during
      its 64,000-fold purification, 32P-labeled guanidovaleryl-Arg-Ala-Ser(P)-isobutyl
      amide (I) was used to measure the cleavage of the Ala-Ser(P) bond. With this
      substrate, kcat was 1.7 s-1 and Km was 30 microM at the pH optimum, 7.5. The
      enzyme was classified as a serine peptidase from its reaction with a set of
      inhibitors, among which diisopropyl fluorophosphate was effective at low (20
      microM) concentration. The endopeptidase showed an Mr of 74,000 under native as
      well as denaturing and reducing conditions, indicating that the native enzyme
      consists of only one major polypeptide chain. The molecular size and inhibition
      profile suggested identity of this enzyme with prolyl endopeptidase (EC
      3.4.21.26). This was supported by its activity against specific substrates, such
      as succinyl-Gly-Pro-Leu-Pro-7-amido-4-methylcoumarin (kcat = 7.2 s-1 and Km = 290
      microM), and by the inhibition of the latter activity by I. Compared with the
      cleavage of 100 microM I, Gly-Val-Leu-Arg-Arg-Ala-Ser-Val-Ala-Gln-Leu, after
      phosphorylation by cAMP-dependent protein kinase, was cleaved at the Ala-Ser(P)
      bond at a relative rate of 0.43, while cleavage of the Ala-Ser bond of the
      unphosphorylated undecapeptide was undetectable, i.e. less than 0.03. The
      pentapeptide Arg-Arg-Pro-Ser-Val was rapidly cleaved at the Pro-Ser bond
      (relative rate, 2.2). Still, the cleavage of the Pro-Ser(P) bond of the
      corresponding phosphorylated pentapeptide was even higher (relative rate, 4.0).
      These data suggest that phosphorylation of a serine residue in the P1' position
      of at least a few substrates of prolyl endopeptidase will increase the rate of
      their cleavage.

PMID- 1995636
TI  - Formation and properties of spectrin containing a truncated beta-chain, generated
      by an endogenous calcium-dependent protease.
AB  - Spectrin chromatographically isolated from human red cell membranes contains a
      proteolytic activity, inhibited by leupeptin, with a dependence on calcium ions
      characteristic of a calpain I. The activity accompanies the spectrin on two
      successive gel filtration columns and is present in both the dimer and the
      tetramer. It is cryptic in the ghost membrane and in purified membrane skeletons
      until these are dissociated, apparently because the spectrin is resistant to
      attack in the tetrameric state. The activity is more strongly expressed in
      spectrin preparations from young than from old cells. Since the bound enzyme does
      not detectably change the elution volume of spectrin in gel filtration, it is
      likely that its molecular weight is low. Its activity reveals itself only in the
      formation of a modified spectrin, lacking the COOH-terminal, phosphorylated
      portion of the beta-chain. The phosphorylated fragment (15-20 kDa) can be
      identified by gel electrophoresis. The proteolytically modified spectrin dimers
      are unable to associate with like molecules, but are univalent with respect to
      formation of hybrid tetramers with native spectrin. The association constant for
      this process is lower than that for self-association of native spectrin by a
      factor of only 2. The proteolytically modified spectrin behaves similarly in this
      respect to a truncated spectrin mutant found in a form of hereditary
      elliptocytosis. The latter also resembles the proteolytic product in that both
      give rise to the same altered NH2-terminal tryptic fragment from the alpha-chain.

PMID- 1995637
TI  - Structural and functional studies on the human interleukin-6 receptor. Binding,
      cross-linking, internalization, and degradation of interleukin-6 by fibroblasts
      transfected with human interleukin-6-receptor cDNA.
AB  - A cDNA coding for the human interleukin-6 receptor (IL-6-R) has been expressed
      stably in murine NIH/3T3 fibroblasts. Transfected cells exhibited a single class
      of binding sites for 125I-labeled recombinant human interleukin-6 (125I-rhIL-6)
      (Kd = 440 pM, 20,000 receptors per cell). Affinity cross-linking of 125I-rhIL-6
      to the IL-6-R-expressing NIH/3T3 cells led to the detection of three 125I-rhIL-6
      containing protein complexes with molecular masses of 100, 120, and 200 kDa
      suggesting a complex organization of the IL-6-R in the plasma membrane. IL-6
      added to the transfected NIH/3T3 cells exerted growth inhibition. This anti
      growth effect was observed by the measurement of cell numbers and ornithine
      decarboxylase mRNA expression. IL-6-R overexpressing fibroblasts internalized
      125I-rhIL-6. Intracellular limited proteolysis of IL-6 could be demonstrated by
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A possible implication
      of skin fibroblasts in the catabolism of IL-6 is discussed.

PMID- 1995638
TI  - Cloning of the cDNA and gene of mouse mast cell protease-6. Transcription by
      progenitor mast cells and mast cells of the connective tissue subclass.
AB  - The cDNA and gene for mouse mast cell protease-6 (MMCP-6) have been sequenced and
      show MMCP-6 to be translated as a prepro-enzyme with a 21-amino acid hydrophobic
      leader peptide, a 10-amino acid activation peptide, and a 245-amino acid mature
      enzyme. The mature form of the enzyme has 73% amino acid sequence identity with
      human and dog mast cell tryptases. The MMCP-6 gene includes 6 exons, with a total
      span of 1.8 kilobases. A 208-base pair intron was defined which separates the 5'
      untranslated sequence of MMCP-6 from the translation initiation codon, thereby
      presenting a gene organization which distinguishes tryptic serine proteases from
      chymotryptic serine proteases of the mast cell secretory granule. By RNA blot
      analysis with a gene-specific probe, MMCP-6 has a unique subclass distribution in
      being transcribed in mouse connective tissue mast cells but undetectable in
      mucosal mast cells. MMCP-6 is the first serine protease of any class to be shown
      to be significantly transcribed in progenitor, bone marrow-derived mast cells,
      which can reconstitute both mucosal mast cell and connective tissue mast cell
      populations in mast cell-deficient mice.

PMID- 1995639
TI  - Activin A/erythroid differentiation factor induces thromboxane A2 synthetic
      activity in murine erythroleukemia cells.
AB  - Activin A, a protein homologous to transforming growth factor beta, was shown to
      induce hemoglobin synthesis in murine erythroleukemia (MEL) cells and was also
      termed erythroid differentiation factor (EDF) (Eto, Y., Tsuji, T., Takezawa, M.,
      Takano, S., Yokogawa, Y., and Shibai, H. (1987) Biochem. Biophys. Res. Commun.
      142, 1095-1103). We found that activin A/EDF also induced thromboxane (TX) A2
      synthetic activity in these cells. Synthesis of TXA2 from arachidonic acid is
      catalyzed by cyclooxygenase and TX synthase. Activin A/EDF induced the latter TX
      synthase activity, whereas the cyclooxygenase activity was constitutively
      expressed. The induction of this enzyme activity was inhibited by cycloheximide,
      suggesting that activin A/EDF induced de novo protein synthesis of TX synthase.
      Furthermore, we studied the relationship between the induction of TXA2 synthetic
      activity and erythroid differentiation in MEL cells, since the former is not an
      erythroid phenotype. We found 1) that the two responses to activin A/EDF were
      distinctly affected by the initial cell density; 2) that the dose-response curves
      for activin A/EDF were similar (ED50 = approximately 100 pM), whereas the time
      course of induction of TXA2 synthetic activity was much faster; and 3) that other
      erythroid differentiation inducers of MEL cells, namely dimethyl sulfoxide and
      hexamethylene bisacetamide, had little or no effect on TXA2 synthesis. These
      results indicate that activin A/EDF induces TXA2 synthetic activity independently
      of erythroid differentiation.

PMID- 1995640
TI  - Characterization and purification of a functional rat glucocorticoid receptor
      overexpressed in a baculovirus system.
AB  - The structure-function relationship of the oligomeric unactivated glucocorticoid
      receptor is not fully understood. An essential step in the process of
      understanding such a relationship involves the production of large quantities of
      the receptor. Using a baculovirus expression system we have been able to
      overproduce a recombinant rat glucocorticoid receptor (rGR). A cDNA coding for
      the entire rGR was introduced into the genome of the wild type baculovirus,
      Autographa californica nuclear polyhedrosis virus, by an in vivo recombination
      event. Based on specific steroid binding, insect cells infected with the
      recombinant baculovirus expressed 1-3 x 10(6) receptor molecules/cell which is 15
      45 times more than that expressed normally in a hepatocyte. The recombinant rGR
      expressed in insect cells is indistinguishable from the bona fide rGR with
      respect to immunogenic reactivity, cytoplasmic localization, sedimentation,
      chromatographic and electrophoretic mobility, and hormone and DNA binding.
      Furthermore, the recombinant rGR is expressed as a functional protein as
      demonstrated by its ability to specifically bind a glucocorticoid agonist, to
      translocate from the cytoplasm to the nucleus upon hormone-binding, and to act as
      a transcriptional enhancer. Pulse labeling of recombinant baculovirus-infected
      insect cells with 32Pi and isolation of the labeled products by
      immunoprecipitation demonstrated that the recombinant rGR is a phosphoprotein.
      Thus, the recombinant rGR expressed in insect cells is biologically active and is
      suitable for structural and functional analysis. A simple three-step purification
      procedure of the unactivated recombinant rGR is described.

PMID- 1995642
TI  - Electron microscopic analysis and biochemical characterization of a novel
      methanol dehydrogenase from the thermotolerant Bacillus sp. C1.
AB  - Methanol dehydrogenase from the thermotolerant Bacillus sp. C1 was studied by
      electron microscopy and image processing. Two main projections can be
      distinguished: one exhibits 5-fold symmetry and has a diameter of 15 nm, the
      other is rectangular with sides of 15 and 9 nm. Subsequent image processing
      showed that the 5-fold view possesses mirror symmetry. The rectangular views can
      be divided into two separate classes, one of which has 2-fold rotational
      symmetry. It is concluded that methanol dehydrogenase is a decameric molecule,
      and a tentative model is presented. The estimated molecular weight is 430,000,
      based on a subunit molecular weight of 43,000. The enzyme contains one zinc and
      one to two magnesium ions per subunit. N-terminal amino acid sequence analysis
      revealed substantial similarity with alcohol dehydrogenases from Saccharomyces
      cerevisiae, Zymomonas mobilis, Clostridium acetobutylicum, and Escherichia coli,
      which contain iron or zinc but no magnesium. In view of the aberrant structural
      and kinetic properties, it is proposed to distinguish the enzyme from common
      alcohol dehydrogenases (EC 1.1.1.1) by using the name NAD-dependent methanol
      dehydrogenase.

PMID- 1995641
TI  - A cluster of four Sp1 binding sites required for efficient expression of the
      human insulin receptor gene.
AB  - Fragments of 5'-flanking sequences of the human insulin receptor gene were
      analyzed in transient expression assays after transfection of cell lines with
      expression assays after transfection of cell lines with an improved low
      background chloramphenicol acetyl-transferase vector system pSVOOCAT (Araki, E.,
      Shimada, F., Shichiri, M., Mori, M., and Ebina, Y. (1988) Nucleic Acids Res. 16,
      1627). Transfection of chimeric chloramphenicol acetyltransferase plasmids
      containing various deletions and insertions of the promoter of HIR gene into CHO
      and COS cells indicated that the region between -629 and -1 (initiator ATG is +1)
      is sufficient for maximal promoter activity. The DNA element of the cluster of
      four G-C boxes (-593 to -618) enhanced the transcription, examined by the low
      background pSVOOCAT vector system in vivo. DNase I footprinting and gel
      retardation experiments using partially purified LacZ-Sp1 hybrid proteins showed
      that the transcription factor Sp1 can bind to the cluster of the four G-C boxes
      of the promoter. Thus, the efficient expression of the human insulin receptor
      gene possibly requires the binding of transcriptional factor Sp1 to four G-C
      boxes located -593 to -618 base pairs upstream of the ATG translation initiation
      codon.

PMID- 1995643
TI  - Purification and characterization of an activator protein for methanol
      dehydrogenase from thermotolerant Bacillus spp.
AB  - All thermotolerant methanol-utilizing Bacillus spp. investigated by us possess a
      NAD-dependent methanol dehydrogenase (MDH) activity which is stimulated by a
      protein present in the soluble fraction of Bacillus sp. C1 cells. This activator
      protein was purified to homogeneity from Bacillus sp. C1 cells grown at a low
      dilution rate in a methanol-limited chemostat culture. The native activator
      protein (Mr = 50,000) is a dimer of Mr = 27,000 subunits. The N-terminal amino
      acid sequence revealed no significant similarity with any published sequences.
      Stimulation of MDH activity by the activator protein required the presence of
      Mg2+ ions. Plots of specific MDH activity versus activator protein concentration
      revealed Michaelis-Menten type kinetics. In the presence of activator protein,
      MDH displayed biphasic kinetics (v versus substrate concentration) toward C1-C4
      primary alcohols and NAD. The data suggest that in the presence of activator
      protein plus Mg2+ ions, MDH possesses a high affinity active site for alcohols
      and NAD, in addition to an activator- and Mg2(+)-independent low affinity active
      site. The activation mechanism remains to be elucidated.

PMID- 1995644
TI  - Human adenovirus serotype 3 fiber protein. Comparison of native and recombinant
      proteins.
AB  - We were able to isolate viral fiber and penton from Ad3-infected KB cells using
      for their detection antibodies obtained against recombinant Ad3 fiber. The native
      material was examined by electron microscopy and the characteristic fiber shape
      of a shaft terminated by a globular head was observed. The native fiber was
      compared with two recombinant fibers synthesized in Escherichia coli cells. One,
      the Ad3 fiber protein expressed in E. coli with a 14-amino acid NH2-terminal
      fusion peptide, under the control of the T7 promoter has been described
      previously. The second is a recombinant Ad3 fiber without the fusion peptide
      (recAd3fib), expressed in the same system. As with the fusion protein recAd3fib
      was found to be insoluble upon expression. It was solubilized in 6 M urea and the
      gradual removal of urea during the purification cycle led to a soluble
      preparation. Biochemical and biophysical studies show that, similarly to fusion
      fiber, recAd3fib self-assembles as trimers in prokaryotic cells. Electron
      microscopy shows that, whereas the fusion fiber consists of a population of
      heterogeneous particles, recAd3fib has the characteristic morphology and size of
      the Ad3 trimeric native fiber. Small angle neutron scattering gives a molecular
      weight consistent with a trimeric fiber and a radius of gyration consistent with
      the dimensions derived from electron microscopy. These results suggest that the
      fusion peptide at the NH2 terminus prevents correct protein folding. They also
      indicate that after solubilization with urea and subsequent renaturation a
      correctly folded eukaryotic oligomeric protein can be produced in E. coli.

PMID- 1995645
TI  - Phosphorylation and subcellular distribution of calpastatin in human
      hematopoietic system cells.
AB  - Calpastatin is an endogenous inhibitor protein acting specifically on calpain (EC
      3.4.22.17; Ca2(+)-dependent cysteine proteinase). The phosphorylation of
      calpastatin was investigated in human hematopoietic system cell lines.
      Microheterogeneity of calpastatin was observed, in which 118- and 116-kDa forms
      were named calpastatin a and b, respectively. The phosphorylation of both
      calpastatins was identified in all cell lines examined and occurred mainly at
      serine residues with trace amounts of phosphothreonine in vivo. The incubation of
      cells with 12-O-tetradecanoylphorbol-13-acetate increased the incorporation of
      32P-orthophosphate into calpastatin a. Two-dimensional maps of 32P-labeled
      phosphopeptide from both calpastatins were identical except for additional minor
      spots for calpastatin a. [35S]methionine-labeled calpastatins a and b were
      localized mainly in the cytosol, and only 6% of cellular calpastatins were
      detected in the membrane fraction. By contrast, more than 30% of the 32P-labeled
      calpastatins a and b were distributed in the membrane fraction. Thus, the
      phosphorylation of calpastatin may be involved in regulating the calpain
      calpastatin protein kinase system by its subcellular distribution.

PMID- 1995646
TI  - Developmentally regulated cytochrome P-450IA1 expression in cultured rat vascular
      smooth muscle cells.
AB  - We have examined the expression of cytochrome P-450IA1 (CypIa1) in cultured rat
      arterial smooth muscle cells (SMC). We report here that newborn (pup) aortic and
      adult carotid neointimal SMC express 10-20-fold higher steady-state levels of
      CypIa1 mRNA compared with identically treated SMC derived from adult aorta or
      uninjured carotid media, respectively. Nuclear transcription experiments suggest
      that the difference in basal expression of CypIa1 reflects differences in
      transcription rates of the gene in these two cell types. Treatment of adult
      aortic SMC with cycloheximide dramatically elevated CypIa1 mRNA levels and had
      little effect on the amount of this mRNA in pup SMC. That the cycloheximide
      effect in adult SMC was due to enhanced transcription of the CypIa1 gene was
      demonstrated by 1) the ability of actinomycin D to completely block the
      cycloheximide-induced increase in steady-state mRNA levels, and 2) the increased
      transcription rate of the CypIa1 gene in cycloheximide-treated adult nuclei
      determined via nuclear transcription assays. Treatment of either cell type with
      beta-napthoflavone increased CypIa1 mRNA levels to a similar extent, suggesting
      that the differential response to cycloheximide was specific and not a general
      lack of pup SMC to respond to transcriptional inducers of the CypIa1 gene. Our
      data suggest that a labile repressor of the CypIa1 gene is present in cultured
      adult aortic SMC and is absent, inactive, or at a greatly reduced level in
      cultured pup SMC.

PMID- 1995647
TI  - Expression of biologically active human antithrombin III by recombinant
      baculovirus in Spodoptera frugiperda cells.
AB  - Antithrombin III (ATIII) is a plasma-borne serine protease inhibitor that plays a
      pivotal role in the regulation of hemostasis. The cDNA for ATIII has been
      available, but genetic studies on the functional domains of ATIII have not
      progressed because of the absence of an expression system that will yield
      sufficient quantities of biologically active protein for biochemical analyses. In
      the present studies the cDNA of the human antithrombin III gene was inserted into
      the vector pVL 1393, which is suitable for cotransfection of Spodoptera
      frugiperda (Sf9) insect cells with Baculovirus wild-type DNA. Recombinant virus
      particles were selected by the presence of occlusion-negative plaques. Upon
      infection with purified recombinant virus, Sf9 cells secreted 10-35 micrograms of
      ATIII/1 x 10(6) cells. Southern analysis of DNA from infected cells demonstrated
      incorporation of the full-length cDNA into the Baculovirus recombinant, and RNase
      protection experiments verified the presence of full-length transcript. This
      recombinant ATIII protein was immunologically reactive with antisera raised
      against native human ATIII, formed stable complexes with thrombin, and was
      heparin-accelerated at the same concentration as native human ATIII. In addition,
      the recombinant ATIII retained specificity for the same molecular species of
      heparin that activates authentic human ATIII. This is the first successful
      production of active, recombinant ATIII in quantities that will allow
      purification on the milligram scale and permit a biochemical analysis of
      genetically engineered variants.

PMID- 1995648
TI  - Characterization of recessive (mediator-) revertants from NIH 3T3 cells
      transformed with a c-H-ras oncogene.
AB  - We have reported earlier the isolation of two recessive, serum- and anchorage
      dependent revertants from an NIH 3T3 line which had been transformed with
      multiple copies of a c-H-ras oncogene. In both revertants the oncogene was fully
      expressed and fusion of either revertant with normal (untransformed) cells or of
      the two revertants with one another resulted in transformed progeny. These, and
      other data indicate that the transforming activity of the c-H-ras oncogene is
      impaired in the two revertants, in consequence of defects in distinct genes
      needed to mediate this activity. Here, we describe some of the biochemical
      features of the revertants. In both of these (as in the transformed line) the
      bulk of the ras-p21 protein was found in the membrane fraction. This suggests
      proper posttranslational processing. Furthermore, no difference was detected
      either in the ras-p21 protein GTPase stimulating activity of GAP or in the extent
      of GAP-tyrosine phosphorylation among growing cultures of the two revertants, the
      transformed line and the parental NIH 3T3 line. The level of glucose transporter
      mRNA was severalfold higher in the transformed line than in the NIH 3T3 line. In
      the two revertants, however, the level was as low as that in the NIH 3T3 line.
      This indicates that the reversion impaired the effect of the c-H-ras oncogene on
      transcription. The raf oncogene (proposed to increase transcription factor
      activity) could retransform both revertants. Moreover, as revealed in experiments
      with growing cultures, neither transformation by the c-H-ras oncogene nor
      reversion from the transformed state altered the electrophoretic mobility of the
      raf protein or the level of its actin kinase activity. These results suggest that
      transformation by the c-H-ras oncogene is not mediated by the activation of raf
      protein kinase. The tyrosine phosphorylation of the p34cdc2 protein kinase (a
      cell cycle regulatory enzyme) was severalfold higher in the transformed line than
      in the NIH 3T3 line. The level of p34cdc2 protein kinase phosphorylation was as
      high in the R260 revertant as in the transformed line and as low in the R116
      revertant as in the NIH 3T3 line. We are attempting to identify the defective
      mediator genes impairing the transforming activity of the c-H-ras oncogene in the
      two revertants.

PMID- 1995649
TI  - Formation of meizothrombin as intermediate in factor Xa-catalyzed prothrombin
      activation on endothelial cells. The influence of thrombin on the reaction
      mechanism.
AB  - Incubation of prothrombin on cultured human umbilical vein endothelial cells with
      factor Xa and calcium ions induced the activation of prothrombin. The mechanism
      of prothrombin activation was analyzed on sodium dodecyl sulfate gels using
      immuno- and amido-blotting techniques. It was demonstrated that meizothrombin was
      formed as an intermediate in prothrombin activation on the endothelial cell
      surface. In addition, considerable amounts of meizothrombin des-fragment-1
      accumulated during prothrombin activation and were not further converted to
      thrombin. Although preincubation of the endothelial cells with thrombin did not
      influence the formation of meizothrombin, addition of hirudin to the prothrombin
      activation mixture inhibited the formation of meizothrombin and meizothrombin des
      fragment-1 almost completely. This indicated that the activity of endogenously
      formed thrombin influenced the formation of meizothrombin via a feedback
      mechanism. The increased formation of meizothrombin and accumulation of
      meizothrombin des-fragment-1 in a latter phase of prothrombin activation points
      to a regulatory mechanism in hemostasis which subdues the formation of the
      procoagulant alpha-thrombin.

PMID- 1995650
TI  - Toxoplasma encephalitis of immunocompetent and nude mice: immunohistochemical
      characterisation of Toxoplasma antigen, infiltrates and major histocompatibility
      complex gene products.
AB  - The experimental infection of immunocompetent and immunodeficient athymic mice
      with an avirulent encephalitogenic Toxoplasma strain (DX strain) was employed to
      study the ensuing encephalitic process by use of histological and
      immunocytochemical methods. In the acute phase of the infection Toxoplasma cysts
      and tachyzoites were accompanied by an infiltrate composed of macrophages, CD4+
      and CD8+ T cells. In the chronic stage a granulomatous encephalitis developed. In
      contrast to immunocompetent NMRI mice, athymic nude NMRI mice died 3 weeks post
      infection because of a generalized toxoplasmosis with predominant involvement of
      the brain. A salient feature of murine Toxoplasma encephalitis was up-regulation
      of class I and II major histocompatibility complex (MHC) gene products. Class I
      antigen was widely expressed on microglial cells and astrocytes. Class II antigen
      was only expressed on microglial cells despite a considerable astrogliosis. Our
      results indicate a differential expression of MHC-determined antigens on brain
      cells in acute and chronic murine Toxoplasma encephalitis.

PMID- 1995651
TI  - Cytolysis of oligodendrocytes is mediated by killer (K) cells but not by natural
      killer (NK) cells.
AB  - The cytotoxic activity of killer (K) cells against enriched cultures of bovine
      oligodendrocytes (BOL) was investigated in multiple sclerosis (MS) and controls.
      Human K cells mediated cytotoxicity to primary cultures of BOL in the presence of
      anti-BOL antiserum in all study groups, while BOL were resistant to human natural
      killer (NK) cells. Cytotoxic activity was significantly reduced in MS when
      compared to age-matched normal controls but not when compared to other neurologic
      disease (OND) patients. K cell-mediated lysis of BOL could also be induced with
      anti-galactocerebroside antibody but not with other antibodies including those
      specific for OL antigens (myelin basic protein, proteolipid apoprotein, and 2',3'
      cyclic nucleotide 3'-phosphodiesterase). Enrichment of the effector population
      indicated that antibody-dependent cell-mediated cytotoxicity (ADCC) to BOL was
      mediated by large granular lymphocytes, and the effector population was further
      characterized by flow cytometry. The effector cells mediating ADCC could be
      inhibited by protein A of Staphylococcus aureus, and by K562 cells in cold
      competition assay. These observations indicate that oligodendrocytes are
      resistant to NK cells but are susceptible to cytolysis mediated by K cells. This
      may represent a potentially important immune mechanism in the pathogenesis of MS.

PMID- 1995652
TI  - Characterization of the specific meningeal T cell response to intracerebral
      inoculation of Theiler's murine encephalomyelitis virus.
AB  - The presence of a resident T lymphocyte population in the meninges of normal
      SJL/J mice has been detected by the use of the T cell-specific mitogen
      concanavalin A. Optimal conditions for [3H]thymidine incorporation were studied.
      An antigen-specific meningeal T cell proliferative response in SJL/J mice, primed
      by intracerebral inoculation of Theiler's murine encephalomyelitis virus, was
      also detected. This response indicated that leptomeningeal mononuclear cell
      infiltrations are involved in the immune response that triggers the demyelinating
      disease.

PMID- 1995654
TI  - Acquaintance rape and alcohol consumption on college campuses: how are they
      linked?
AB  - This article explores the links between acquaintance rape and alcohol consumption
      among college students. Both heavy drinking and acquaintance rape are serious
      problems on college campuses, and they frequently co-occur. Seven explanations
      for the relationship between alcohol consumption and acquaintance rape are
      provided: three of these explanations focus on alcohol consumption by the
      perpetrator and four focus on alcohol consumption by the victim. The need to
      conduct studies and develop prevention programs that address these issues is
      discussed.

PMID- 1995655
TI  - The role and function of drinking games in a university community.
AB  - Understanding the role of drinking games in college student life is critical for
      program planners who wish to develop education and prevention programs to reduce
      abusive drinking. Drinking games are popular social activities that provide a
      focus for social interactions but place students at considerable risk for serious
      consequences. This article reports preliminary results of a study using
      participant observation and in-depth interviews to develop a typology of drinking
      games and describe patterns and practices associated with the games.

PMID- 1995653
TI  - Monoclonal antibodies to oxytocin: production and characterization.
AB  - To induce a good immune response to oxytocin (OT) we developed a two-step
      technique to conjugate OT to thyroglobulin (TG) using glutaraldehyde. We obtained
      30 hybridomas recognizing OT-ovalbumin conjugates and 16 stable lines. Three
      monoclonal antibodies were selected for further characterization. One of them
      (O13) was found very specific for OT using three different techniques (enzyme
      linked immunosorbent assay, radioimmunoassay and immunohistochemistry); it is
      directed to the C-terminal tripeptide. The other two probably recognize tyrosine
      containing epitope(s) also shared by vasopressin and other related nonapeptides.

PMID- 1995656
TI  - The adequacy of college health insurance coverage.
AB  - This analysis of private health insurance plans offered in 100 four-year colleges
      and universities in 1988 indicates a tremendous diversity in plan options,
      benefits covered, cost-sharing requirements, and catastrophic protections.
      Consistent with relatively low premium prices, most student health insurance
      plans offer limited benefits and expose students to significant out-of-pocket
      medical cost liabilities. Only a minority of schools use financial incentives,
      such as preferred provider arrangements, to integrate their health insurance
      plans with their university health service system. We conclude that universities
      should carefully reexamine the adequacy of their health insurance plans and their
      relationship to student health centers. As more students rely on student health
      insurance as their only source of coverage, the quality of these plans assumes an
      even greater importance.

PMID- 1995658
TI  - From data to program decisions: developing a student assistance program.

PMID- 1995657
TI  - Testicular self-examination by young men: an analysis of characteristics
      associated with practice.
AB  - This study was conducted to determine the level of testicular self-examination
      (TSE) awareness and practice and to identify characteristics related to TSE
      awareness and practice in a sample of college men. A 26-item survey was
      administered to 404 male college students. Forty-two percent reported they were
      aware of TSE, more than 41% had been taught TSE, and 22% had examined their
      testicles at least once in their lifetime. Approximately 8% of the study
      population reported practicing TSE once a month. The PRECEDE model was used to
      categorize the significant variables that influenced monthly TSE practice. Age
      and college class were significant demographic variables; predisposing factors
      included having heard of testicular cancer, knowing about recommended practice
      rates, feeling that cancer can be controlled, and awareness of the risk factors
      associated with testicular cancer. Having been taught TSE was the statistically
      significant enabling factor. A discussion of TSE in the past 6 months was the
      significant reinforcing factor.

PMID- 1995659
TI  - Signing on for health: initiating a computerized health information bulletin
      board.

PMID- 1995660
TI  - College health and fast-food values.

PMID- 1995662
TI  - Advertising in medical journals ... and beyond.

PMID- 1995661
TI  - The American Medical Women's Association and the role of the woman physician,
      1915-1990.

PMID- 1995663
TI  - Open hand fractures: prognosis and classification.
AB  - Two hundred open fractures distal to the carpus in one hundred twenty-one
      patients were studied retrospectively. One hundred seventy-three fractures were
      followed-up to complete bony union, which occurred at a median period of seven
      weeks. Ninety-seven total complications included nine wound infections in seven
      patients, eighteen malunions, seventeen delayed or nonunions, twenty-three
      fixation problems, and two late amputations. Infection rate increased in the
      presence of wound contamination, delay in treatment greater than twenty-four
      hours, or systemic illness. It was not increased by presence of internal
      fixation, immediate wound closure, large wound size, tendon/nerve/vascular
      injury, or high-energy mechanism. We suggest a classification predictive of
      infection: type I: Clean wound and no systemic illness; type II: Contaminated
      wound, delay in treatment greater than twenty-four hours, or significant systemic
      illness. We recommend choosing fracture stabilization on the basis of the
      mechanical needs of the fracture, regardless of wound size, injury energy, or
      contamination. Immediate wound closure is appropriate for type I injuries and
      delayed closure should be reserved for type II wounds.

PMID- 1995664
TI  - Infections in open fractures of the hand.
AB  - We reviewed one forty-six consecutive cases of patients with open fractures of
      the hand to identify factors that predict infection and poor outcome. The
      incidence of infection was 11%. The infection rate in type 1 open fractures was
      0%; in type 2, 9%; and in type 3, 14%. Infection occurred in 20.5% of grossly
      contaminated wounds (p less than 0.02), and was most common in patients with
      extensive soft tissue and skeletal injury. Delay in treatment did not increase
      the incidence of infection or affect outcome. Functional outcome was highly
      correlated with the initial fracture type and with the presence of infection.
      Preoperative wound cultures were of no value in predicting the risk of infection
      or the nature of the likely pathogen. Patients with severe open fractures should
      be warned of the risk of infection, prolonged convalescence, and permanent
      impairment.

PMID- 1995665
TI  - Unstable phalangeal fractures: treatment by A.O. screw and plate fixation.
AB  - A prospective study of fifty-two fresh traumatic unstable fractures of the
      proximal or middle phalanges of the hand in forty-seven patients was reviewed.
      All the fractures were fixed with A.O. miniature screws and plates. The overall
      results were not satisfactory and complications were frequent. Only 26.9% of the
      fractures had good results. Fractures associated with significant soft tissue
      injuries had very poor results. When the present series was compared with a
      comparable group of fractures fixed with Kirschner wires, there was no
      significant improvement in the results. The unsatisfactory outcome of this group
      of unstable fractures may be largely due to the frequent association with poor
      prognostic factors.

PMID- 1995666
TI  - Rotating shaft avulsion amputations of the thumb.
AB  - In a three-year period twenty-nine patients were treated for rotating shaft
      avulsion amputations of the thumb. Twenty-three thumbs were considered suitable
      for replantation. A staged approach, consisting of primary replantation and
      secondary nerve grafting and tendon reconstruction, was used because of concern
      that survival rates would be low. Survival was achieved in nineteen of twenty
      three replantations. At mean follow-up of 20.5 months grip strength was 94.6% of
      the unaffected side and key pinch was 77.1%. Five patients achieved a two-point
      discrimination less than five millimeters. Success was better anticipated and now
      a full reconstruction is carried out in a single-stage procedure.

PMID- 1995668
TI  - Irreducible dorsoulnar dislocation of the proximal phalanx of the thumb.
AB  - A case of irreducible complete dorsoulnar dislocation of the proximal phalanx of
      the thumb is presented. The pathologic anatomy included intersubstance tears of
      the ulnar collateral ligament and dorsal capsule and avulsions of the palmar
      plate and radial collateral ligament from their metacarpal attachments. The
      palmar plate blocked reduction, as did the radial collateral ligament that was
      caught on the margin of a tear in the adductor aponeurosis and on the tendon of
      the extensor pollicis longus. A review of the English-language literature
      indicates that this pathologic anatomy has not been described.

PMID- 1995667
TI  - Technical considerations in pectoralis major transfer for treatment of the
      paralytic elbow.
AB  - Modification of pectoralis major transfer as originally described by Clark in
      1946 have not addressed concerns such as diminished strength and excursion of the
      transfer, along with obligatory supination of the forearm. Postoperative scarring
      from the long oblique chest incision further compounds the psychological
      impairment that accompanies brachial plexopathy. One hundred forty-three brachial
      plexopathies were seen over a five-year period. Seven pectoralis major transfers
      were done to restore elbow flexion in patients with C5-6 and C5-6-7 cord
      injuries. Mean age and follow-up were 26 years and 25 months respectively. The
      modifications of this transfer we use improve strength and range of motion by
      preserving dual innervation of the muscle, by tubularization of the transfer, and
      by restoration of the transverse aponeurosis as a fascial pulley. By transfer of
      the pectoralis insertion to the acromion, further anterior shoulder stability may
      be obtained. Aesthetics can also be improved by use of selected midline and
      deltopectoral incisions, along with preservation of the remaining pectoralis
      major and minor.

PMID- 1995669
TI  - Incidence of brachydactyly and hand exostosis in hereditary multiple exostosis.
AB  - Forty-two radiographs and charts of twenty-two patients with a diagnosis of
      hereditary multiple exostosis and hand involvement were examined to determine the
      incidence of hand exostoses and association with brachydactyly. An average of
      11.6 exostoses were found per hand. The proximal phalanges and metacarpals are
      affected in the majority of patients and the thumb and distal phalanges are
      rarely involved. Most exostoses were located in the juxtaepiphyseal region
      (61.8%) and typically involved less than 50% of the bone diameter. Brachydactyly
      can be seen in patients with hereditary multiple exostosis when no exostoses is
      present; however, the presence of an exostosis results in even more shortening.
      The location and size of the exostosis had no relationship to increased bone
      shortening. Operative treatment was required in four of twenty-two patients for
      debulking and impingement.

PMID- 1995670
TI  - Thumb duplication and contralateral thumb hypoplasia in infant of mother with
      diabetes.
AB  - Uncontrolled maternal diabetes frequently results in congenital anomalies. This
      report describes an infant of a mother with diabetes born with thumb hypoplasia
      and contralateral thumb duplication without other associated anomalies. Maternal
      diabetes should be part of the etiologic differential diagnosis of thumb
      anomalies. The concomitant occurrence of thumb duplication and hypoplasia,
      apparently as a result of the same systemic insult, suggests a close relationship
      between hypoplasia and duplication.

PMID- 1995672
TI  - Bone grafting unnecessary in the treatment of enchondromas in the hand.
AB  - Twenty-eight consecutive patients with enchondromas in the hand skeleton had
      simple curettage of the tumor without bone grafting. The patients were followed
      up with a radiologic examination mean six years (range from 0.5 to 16 years)
      after operation. Results were classified according to the amount of new bone
      formed in the cavity left after curettage. Results in fifteen patients with
      excellent bone formation were classified as grade one, in nine patients with good
      bone formation as grade two, and in four patients with scanty bone formation as
      grade three. There were no patients without new bone formation (grade four), nor
      were there any recurrences or postoperative fractures in this series. We conclude
      that simple curettage without bone grafting is a safe and effective treatment of
      enchondromas in the hand.

PMID- 1995671
TI  - Swine bites of the hand.
AB  - Severe infections of the hand may follow bites by swine who carry a wide range of
      gram-negative and gram-positive flora. Early treatment must be primarily
      surgical, with prompt and thorough wound cleansing, superficial and deep
      debridement of the wound, drainage, and delayed closure of wounds only after
      cultures show no bacterial growth. Appropriate antibiotics are especially
      important with local or systemic symptoms of infection, as well as
      prophylactically. An illustrative case is presented.

PMID- 1995673
TI  - A protocol for tissue expansion in upper extremity reconstruction.
AB  - Twenty tissue expanders were used in twelve patients for reconstruction of the
      upper extremity after trauma or burns with extensive soft tissue loss. A
      protocol, designed to avoid complications, included defects not exceeding thirty
      percent of the arm circumference, use of low-profile expanders, and slow
      expansion. Attention to these details avoided all complications except for
      transient neuropathies.

PMID- 1995674
TI  - Junctional nevus of the nailbed germinal matrix.
AB  - An uncommon case of junctional nevus of the germinal matrix of a fingernail in a
      young, white male is described. The patient's complaints were suggestive of
      malignant transformation of a nevus and excisional biopsy with primary
      reconstruction was done. This case illustrates the necessity for biopsy of
      pigmented nail lesions in white subjects for accurate diagnosis and proper
      treatment.

PMID- 1995675
TI  - Reverse forearm flap based on an "exteriorized" pedicle.
AB  - Soft tissue coverage after multiple digital amputations was achieved with a
      reverse forearm flap based on an "exteriorized" vascular pedicle. The length of
      exposed radial artery pedicle was calculated to permit full range of motion of
      the involved digits before flap division and inset. No complications of the
      exposed vascular pedicle were noted.

PMID- 1995676
TI  - Vascularized single toe joint transfer to the hand.
AB  - We report a retrospective review of our series of thirty-one single joints
      harvested from the toe in twenty-six patients and transferred to the
      metacarpophalangeal or proximal interphalangeal joint of the finger. Twenty-six
      transfers were done in traumatic cases and five in congenital. Follow-up averaged
      22.6 months. Average range of motion was from 17.1 degrees to 44.3 degrees, with
      an arc of 27.2 degrees. The congenital group had an average motion ranging from
      14.4 degrees to 27.2 degrees and an arc of 12.8 degrees. The traumatic group's
      motion was from 17.6 degrees to 47.6 degrees and an arc of 30.0 degrees.
      Complication rates were significant, with fifty percent of the patients
      experiencing one or more complications. Although vascularized joint transfer is a
      demanding procedure, it provides a reasonable alternative to arthrodesis and with
      further refinement in technique may become a reliable treatment option.

PMID- 1995677
TI  - Transcutaneous blood flow measurements in arteries of the human hand.
AB  - Technical advances in twenty MHz pulsed ultrasonic Doppler velocimetry (PUDVM)
      permit increasingly accurate measurements of blood flow in small vessels. This
      study applied advanced twenty MHz PUDVM methods to the transcutaneous,
      noninvasive quantitation of blood flow in arteries of the human hand. One hundred
      forty-four measurements were completed bilaterally in the digital arteries of all
      fingers and in the distal radial and ulnar arteries of the forearm. The data were
      averaged by artery for maximum velocity and average volumetric flow. The maximum
      velocity for digital and forearm arteries was about 20 centimeters per second and
      50 centimeters per second, respectively. The average volumetric flow for these
      same arteries was about 0.02 cubic centimeters per second and 0.18 cubic
      centimeters per second, respectively. Statistical analysis demonstrated no
      differences between paired, contralateral arteries; within given fingers a
      difference occurred only between the radial and ulnar arteries of the index
      finger.

PMID- 1995678
TI  - Dynamic pressure therapy for scars in the finger web spaces.

PMID- 1995679
TI  - A new instrument: a carpal tunnel knife.

PMID- 1995680
TI  - Psoriatic arthritis and Koebner phenomenon.

PMID- 1995681
TI  - "Nintendinitis".

PMID- 1995682
TI  - Modified forearm intravenous regional analgesia for hand surgery.

PMID- 1995683
TI  - Aeromonas hydrophilia infection complicating digital replantation and
      revascularization.

PMID- 1995684
TI  - Ulnar nerve neurolysis.

PMID- 1995685
TI  - Manipulation of the stiff elbow with patient under anesthesia.
AB  - Eleven patients had elbow manipulation under general anesthesia to improve a
      dysfunctional range of motion. Six (55%) patients improved their motion, three
      (27%) patients had no significant change, and two (18%) patients lost motion.
      Type of injury, extremity dominance, previous surgical procedures, delay to
      manipulation, or use of postoperative steroid injections and continuous passive
      motion did not correlate with successful results. Two transient sensory ulnar
      neuropathies were the only complications and no heterotopic bone formation or
      exacerbation was observed. Manipulation under anesthesia should be considered in
      patients with a dysfunctional elbow range of motion after failure of well
      supervised rehabilitation.

PMID- 1995686
TI  - Detection of foreign bodies in the hand.
AB  - Fresh cadaver hands were used to compare the ability of routine x-ray,
      xeroradiography, computerized tomography, and magnetic resonance imaging to
      identify a variety of foreign bodies including glass, gravel, plastic, and wood
      in the soft tissue of the hand. All types of glass were easily seen by all
      imaging methods. Gravel foreign bodies were visible with all methods except
      magnetic resonance imaging where ferromagnetic streak artifacts obscured
      visualization. Plastic, although not seen by routine x-ray or xeroradiography,
      was faintly seen by computed tomography, and easily detected by magnetic
      resonance imaging. Wooden foreign bodies, especially when wet, were seen only by
      computed tomography and magnetic resonance imaging. Xeroradiography had no
      benefit over plain films in identifying foreign bodies and should be discarded in
      favor of computed tomography or magnetic resonance imaging when plain films are
      unrevealing. A practical guide for identifying foreign bodies in the soft tissues
      of the hand is presented.

PMID- 1995687
TI  - Intrinsic healing of the laceration site in human superficialis flexor tendons in
      vitro.
AB  - The intrinsic capability of the human superficialis flexor tendon to heal a
      reapproximated laceration site in vitro was examined. Segments of lacerated and
      sutured human superficialis flexor tendons from zone II were cultured for two,
      four, or eight weeks in vitro and analyzed by use of light and electron
      microscopy. We noted a specific pattern of intrinsic healing at the repair site
      during the incubation period. After two weeks, the cells of the epitenon from
      both tendon stumps proliferated and appeared to migrate into the repair site.
      Elongated cells of the thickened epitenon bridged the laceration and synthesized
      new collagen fibers. By eight weeks, a smooth contiguous tendon surface was
      restored and the internal collagen bundles were brought into intimate contact.
      The fibroblasts bridging the laceration, both in the epitenon and centrally in
      the repair site, were oriented perpendicular to the cut surfaces. The cells in
      the repair site were active in protein synthesis, and new collagen fibers were
      present. No cellular necrosis was observed in the internal repair site. Our
      results indicate that human superficialis tendons possess an intrinsic capacity
      to heal with diffusion and without dependence on extratendinous cells or on
      adhesions.

PMID- 1995688
TI  - Tendon subluxation after de Quervain's release: treatment by brachioradialis
      tendon flap.
AB  - Volar subluxation of the tendons of the first dorsal compartment of the wrist
      occurred in two patients after surgery for treatment of de Quervain's stenosing
      tenosynovitis. In both patients a painful tenosynovitis of the extensor pollicis
      brevis and abductor pollicis longus developed, which was unresponsive to
      conservative therapy as the tendons prolapsed over the prominence of the first
      dorsal compartment. A distally based flap of the brachioradialis tendon was used
      to prevent tendon prolapse, with both patients asymptomatic and free of
      subluxation one and five years after operation.

PMID- 1995689
TI  - Fibrous loose body in the flexor tendon sheath.
AB  - We report the first known example of an entirely fibrous loose body lying in the
      flexor tendon sheath of a finger. This was seen initially as a painless swelling
      in a fit young woman and was surgically excised with full restoration of
      function. The cause of the loose body is unknown, but it may have originated as a
      fibroma of the flexor tendon sheath or as a localized nodular tenosynovitis.

PMID- 1995690
TI  - Relationship between radial inclination angle and ulnar deviation of the fingers.
AB  - Fifty wrists (thirty-two patients) with rheumatoid arthritis and ulnar drift of
      the fingers were examined radiologically and compared to fifty normal wrists
      radiographs. Statistically significant differences were found for measurements of
      radial inclination angle, carpal-radial distance, third metacarpal-phalangeal
      angle, and carpal height ratio. Third metacarpal-phalangeal angle of ten degrees
      or greater on standard posteroanterior radiograph appears to accurately represent
      digital ulnar drift. Elevated radial inclination angle was highly correlated with
      digital ulnar drift (p much less than 0.001). Radial inclination angle greater
      than twenty-two degrees is associated with the development of digital ulnar drift
      through two mechanisms, radial carpal rotation, and ulnar carpal translocation.

PMID- 1995691
TI  - Radial styloidectomy: an anatomical study with special reference to radiocarpal
      intracapsular ligamentous morphology.
AB  - This study determines the anatomical relationship of the radiocarpal ligaments to
      the radial styloid process, and the effect of three specific styloidectomies on
      the integrity of these ligaments. Thirty fresh cadaveric wrists were dissected.
      The origins, insertions, and dimensions of each ligament was determined. The
      thirty wrists were divided randomly into three equal groups and the ten wrists in
      each group had three types of styloidectomy: short oblique, vertical oblique, and
      horizontal. The styloid fragments and wrists were then reexamined to determine
      the integrity of the ligaments. All styloidectomies removed the radial collateral
      ligament origin. Vertical oblique styloidectomy removed additionally 92% of the
      radioscaphocapitate and 21% of the radiolunatotriquetral ligament. Horizontal
      styloidectomy removed 95% of the radioscaphocapitate, and 46% of the
      radiolunatotriquetral ligament. These findings indicate that the degree of
      radiocarpal ligament disruption that occurs after styloidectomy may be predicted
      accurately by correlating the amount of styloid removed, with the consistent
      ligamentous anatomy of this area.

PMID- 1995693
TI  - Anatomic course of the medial cutaneous nerves of the arm.
AB  - The medial antebrachial cutaneous nerve and the medial brachial cutaneous nerve
      were dissected in twenty fresh cadaver extremities. These nerves have a variable
      number of cutaneous branches ranging from four to twelve, with an average of
      eight. Branches always originated medially in both nerves and ran in an
      anterolateral direction. In all the medial antebrachial cutaneous nerves, there
      were three to five terminal branches directly overlying the medial epicondyle and
      supplying the skin over the olecranon. The course of this nerve is predictable
      relative to the basilic vein and the medial epicondyle. There was a ninety
      percent incidence of communication between the medial brachial cutaneous nerve
      and the intercostobrachial cutaneous nerve. The standard incision used for
      surgery of the ulnar nerve at the elbow will cut the terminal branches of the
      medial antebrachial cutaneous nerve one hundred percent of the time, and the
      terminal branches of the medial brachial cutaneous nerve eighty percent of the
      time, if they are not identified. A posterior approach for transposition of the
      ulnar nerve would avoid damage to these nerves.

PMID- 1995692
TI  - Radiographic changes in wrists with ulnar plus variance observed over a ten-year
      period.
AB  - This study provides additional radiographic information concerning the long-term
      effect of ulnar impingement. Films of 198 wrists of 102 patients with vibration
      disease observed over ten or more years were reviewed. All the wrists showed
      ulnar plus variance of more than 0 mm except seven. Degenerative changes were
      found in 58 wrists and were seen only on the ulnar side of the wrist, especially
      in the ulnoproximal area of the lunate. Most of the degenerative changes in the
      wrists with ulnar plus variance had progressed or changed during the ten or more
      years. Ulnar plus variance may play an important role in inducing or causing
      progression of degenerative change in the wrist.

PMID- 1995694
TI  - Fascicular topography of the median nerve: a computer based study to identify
      branching patterns.
AB  - This study was undertaken to definitively describe the internal anatomy of the
      median nerve. Thirty median nerves were dissected in the distal forearm and hand.
      Sixteen nerves were sectioned every 250 to 1000 microns along their length.
      Computer programs were developed in our laboratory to digitize and store the
      data. Analysis of our data has shown the following consistent findings: (1) the
      number of fascicles remains relatively constant over the centimeter lengths of
      the nerve; (2) over 75% of the sections contain zero to one fascicular branching;
      (3) fascicular groups destined for the same endpoint remain localized within the
      nerve for long distances; and (4) calculation of Wilks' lambda demonstrates a
      high degree of group fascicular regionality.

PMID- 1995696
TI  - Recovery from symptoms after carpal tunnel syndrome surgery in males in relation
      to vibration exposure.
AB  - A follow-up study was conducted in forty-one men (fifty-five hands) treated
      surgically for carpal tunnel syndrome. The number of hours of vibration exposure
      and exactly which hand tool was used were recorded and each tool was categorized
      according to vibration level. The patients were divided into a low exposure and a
      high exposure group. Age at surgery, mean distal latency in the median nerve, and
      the duration between onset of symptoms and surgery were similar for the two
      groups. Only one patient experienced nocturnal paresthesia at follow-up in the
      low exposure group in contrast to twelve in the high exposure group. This
      corresponded to an age-standardized odds ratio (relative risk) of eighteen for
      nocturnal paresthesia after surgery in the high exposure group, with the low
      exposure group as referents. Previous vibration exposure may influence the
      recovery after carpal tunnel surgery.

PMID- 1995695
TI  - Successful reeducation of functional sensibility after median nerve repair at the
      wrist.
AB  - The effect of sensory reeducation was evaluated in a group of twenty-two adult
      patients who had a repair of a clean-cut median nerve at the wrist. These results
      were compared with the sensibility in a group of twenty-four adults with repair
      of clean-cut median nerve at the wrist who had never received sensory
      reeducation. The reeducation group were evaluated between one and two years from
      the time of their median nerve repair. The control patients were retrospectively
      evaluated between one and sixteen years after their nerve repair. The effect of
      reeducation on improving the paresthesias that accompany neural regeneration was
      also evaluated. Sensibility was determined by an object recognition test and by
      measurement of static and moving two-point discrimination. The results
      demonstrated that sensory reeducation significantly (p less than 0.01) diminished
      the severity of postoperative paresthesias. It also gave significantly better
      improvement in moving two-point discrimination than in static two-point
      discrimination within the timeframe evaluated (p less than 0.002). Excellent
      recovery of sensibility, as determined by ability to recognize nine or more
      objects out of twelve, was significantly greater (p less than 0.005) for the
      sensory reeducation group than at any time interval beginning after six months
      after nerve repair. It is concluded that a program of sensory reeducation after
      median nerve repair at the wrist in adults minimizes discomfort and improves
      sensibility in the postoperative period.

PMID- 1995697
TI  - Granular cell tumor of the palmar cutaneous branch of the median nerve.
AB  - Granular cell tumor rarely occurs in the hand. A patient with this tumor
      involving the palmar cutaneous branch of the median nerve, and twelve-month
      follow-up is discussed. This lesion, similar to neurofibromas, can infiltrate
      peripheral nerves and cannot be dissected from them. The lesion is probably of
      Schwann cell origin.

PMID- 1995698
TI  - Stress computed tomography analysis of the distal radioulnar joint: a diagnostic
      tool for determining translational motion.
AB  - Sixteen distal radioulnar joints in eight normal volunteers (five females, three
      males) were evaluated by use of a special stress computed tomography technique.
      The mean palmar and dorsal translational motion was 2.2 millimeters +/- 1.6 and
      1.0 millimeters +/- 0.9, respectively, for the combined group. The mean stress
      range was 3.3 millimeters +/- 1.4 for the entire group. There was no statistical
      difference for the amount of motion noted on palmar stress, dorsal stress, and
      the stress-range between males and females. There was also no statistical
      difference between contralateral sides and hand dominance. The average
      contralateral difference was 0.1 millimeters, 0.1 millimeters, and 0.3
      millimeters for palmar, no stress, dorsal studies, respectively. We conclude the
      limits of maximal translational motion of the distal radioulnar joints can be
      determined by computed tomography stress analysis. Unilateral analysis allows the
      determination of frank instability. However, bilateral analysis allows the
      determination of frank instability, subluxation, and dynamic instability. This
      technique is useful in evaluating distal radioulnar joint stability.

PMID- 1995699
TI  - Carpal orientation from computed reference axes.
AB  - Carpal instability is usually diagnosed by abnormal two-plane radiographic
      angles. These angles are often unreliable. A method that eliminates
      interpretation of overlapping shadows and uses all of the carpal geometry should
      improve clinical diagnoses. The digital data from computed tomography scans can
      be manipulated to describe the carpal orientation in the normal wrist. The
      digital data from the computed tomography scans of twenty-two normal wrists were
      used to compute distances with and without directions between the volumetric
      centroids of the carpal bones. An expansion technique also extracted from the
      computed tomography data an orthogonal set of vectors, the principal axes. The
      first principal axis describes the longest dimension of each bone. The average
      angle produced by the first principal axes of the scaphoid and lunate was 23.6
      degrees, scaphoid and capitate was 73.2 degrees, and the capitate and the lunate
      was 93.5 degrees. These computations represent new carpal axes and intercarpal
      angles that are not related to the commonly measured two-plane radiographic
      angles. They should prove helpful in the study of kinematics and pathomechanics
      in the wrist joint.

PMID- 1995700
TI  - The silicone scaphoid: a biomechanical study.
AB  - Five fresh cadaver upper extremities were studied by use of a static positioning
      frame, pressure-sensitive film, and a microcomputer-based videodigitizing system,
      to assess the load-bearing characteristics of a scaphoid silicone implant within
      the radioulnarcarpal joint. Specimens were studied in their "normal" condition,
      after resection of the scaphoid, after placement of a scaphoid implant, and with
      a scaphoid implant and a simulated capitate-lunate-triquetrum-hamate fusion. The
      scaphoid silicone implant bore significant, although less, load than the normal
      scaphoid. Decreasing the size of the scaphoid implant decreased the load born by
      the implant. Decreased load through the scaphoid implant was compensated by the
      lunate. The addition of a limited carpal fusion did not significantly decrease
      the load born by a scaphoid implant. Therefore, the silicone scaphoid implant is
      a load-bearing implant even when undersized or placed in association with a
      limited carpal fusion.

PMID- 1995701
TI  - Diagnosis of an anomalous superficialis muscle in the palm by magnetic resonance
      imaging.
AB  - Anomalous muscles of the upper extremity are encountered occasionally and in most
      cases, identification has been made at operation. Plain radiographs do not
      visualize soft tissues well. Magnetic resonance imaging provides good definition
      of soft tissue structures. We report a case of an anomalous flexor digitorum
      superficialis muscle in the palm, that was seen initially as a mass associated
      with a previous injury and pain. Magnetic resonance studies showed the mass to be
      a muscle belly in the palm. Preoperative identification of anomalous muscles is
      possible with magnetic resonance imaging.

PMID- 1995702
TI  - FPLC purification of mouse monoclonal antibodies from ascitic fluid using blue
      DEAE and thiophilic sorbents.
AB  - Two fast methods for the purification of mouse monoclonal antibodies from
      ascites, fluids using Blue-DEAE and 'thiophilic' adsorbent (T gel) in the FPLC
      system are described. Blue-DEAE chromatography is useful only for IgG1, IgG2a and
      IgG2b monoclonal antibody purification. T gel is a satisfactory adsorbent for
      IgG2b purification. Other IgG subclasses and IgM can also be obtained by simple
      one-step procedures, but the preparations contain small amount of high molecular
      weight contaminants.

PMID- 1995703
TI  - A solid phase enzyme immunoassay for serum amyloid A (SAA) protein. Clinical
      evaluation.
AB  - An enzyme-linked immunosorbent assay for serum amyloid A protein using
      commercially available antisera has been developed. Immulon II microtitre plates
      are coated with undenatured sera by overnight incubation at 4 degrees C. The
      assay combines the advantages of simplicity, rapidity, precision, sensitivity and
      safety and confirms the suitability of measuring serum amyloid A protein as a
      sensitive marker during the acute-phase response. This method permits the rapid
      processing of a large number of samples.

PMID- 1995704
TI  - An alternative statistical treatment for summarizing the central tendency of
      replicate assay data.
AB  - Standard assay procedures call for multiple replicates for the purpose of
      averaging random error from individual replicate scores to obtain a reliable
      estimate of the true score and for the purpose of specifying the degree of
      variability within the assay. In this paper we focus on the variability and
      magnitude of within-assay replicates in order to improve the estimate of the true
      score. A rule is presented for deciding (1) when individual replicates should be
      omitted from the computation of the assay's summary score or (2) when an entire
      sample of replicates should be discarded based on the pattern of replicate
      scores. It is suggested that this rule improves the reliability of the estimated
      assay score and this is supported by an illustrative analysis of lymphocyte
      proliferation assays.

PMID- 1995705
TI  - An improved dot immunobinding assay for screening hybridoma supernatants. Non
      purified antigen immobilized on nitrocellulose paper discs.
AB  - This report describes a modified dot immunobinding assay (DIA) in microplates
      using a crude mixture of non-purified antigen. Nitrocellulose filter paper discs
      exposed to the antigen mixture were inserted into the wells and kept in place by
      a specially constructed device. To test the efficiency of the modification a set
      of monoclonal antibodies from a mouse immunized with 58 kDa trpE-Bmyc fusion
      protein were screened. The advantage of this modified method over conventional
      ELISA is that it permits the use of non-purified antigen for screening large
      numbers of monoclonal antibodies.

PMID- 1995706
TI  - The use of recombinant antigens in ELISA procedures for the quantification of
      intrathecally produced HIV-1-specific antibodies.
AB  - An ELISA procedure is described for the quantification of intrathecally
      synthesized immunoglobulin G antibodies to human immunodeficiency virus (HIV)
      antigens. Recombinant p17, p24, endonuclease (END), reverse transcriptase (RT), a
      peptide from the transmembrane region of gp41 (ENV80) and a fusion protein
      containing HIV-1 and HIV-2 epitopes were compared with a commercially available
      ELISA. Using a reference serum, antibodies in serum and cerebrospinal fluid (CSF)
      to all of the antigens could be measured quantitatively in a reliable and
      reproducible fashion. Despite the fact that the titer varied up to 10(5)-fold
      between CSF and serum, interassay variability ranged from 3.87% for p17 to 8.41%
      for RT and intra-assay variability varied from 3.9% +/- 1.2% for p17 to 14.3% +/-
      3.9% for the commercial ELISA. Antibody specificity indices (ASI) obtained by
      relating CSF/serum titers with reference to the corresponding IgG concentrations
      can be used to detect intrathecal synthesis of virus specific antibodies.

PMID- 1995707
TI  - Antibodies in water immiscible solvents. Immobilized antibodies in hexane.
AB  - Anti-progesterone antibodies covalently coupled to paramagnetic particles (PMPs)
      retain their immunologic activity to progesterone in hexane as solvent. Although
      reaction rates appear slowed, activity is not lost. The antibodies still bind
      similar quantities of antigen to those bound in aqueous solution. It is most
      likely that the increased reaction time is the result of a phase transfer. The
      immobilized antibodies are present in an aqueous phase, while the antigen is
      present in the more soluble organic solvent phase.

PMID- 1995708
TI  - An enzyme-linked immunosorbent assay for the determination of bovine prolactin in
      plasma.
AB  - Highly purified pituitary bovine prolactin (bPRL) has been used in a sensitive
      non-competitive enzyme-linked immunosorbent assay of prolactin (PRL)
      concentrations in plasma. In this assay affinity purified polyclonal antibodies
      were immobilized to the solid phase in order to capture the antigen, and were
      also used biotinylated as the detector antibody. The method was found to be
      reproducible (3% variability between calibration curves) and has been optimized
      for measuring bPRL concentration in plasma samples, giving an intra-assay
      coefficient of variation of about 5% and an interassay coefficient of variation
      of about 9%. The sensitivity of the assay was found to be as low as 0.1 ng/ml of
      bPRL.

PMID- 1995709
TI  - Preparation and characterization of polyclonal and monoclonal antibodies to
      polyamines.
AB  - In order to develop an immunocytochemical method suitable for the study of the
      cellular localization and intracellular distribution of polyamines we have
      prepared and characterized antibodies to polyamines. Artificial immunogens were
      prepared by coupling putrescine, spermidine and spermine to a carrier protein.
      Immunogens containing bovine serum albumin as a carrier protein were used to
      immunize rabbits (polyclonal antibodies) and mice (for the production of Mabs).
      The specificity of the antibodies was tested in an ELISA system utilizing
      antigens synthesized from thyroglobulin and one of the polyamines. Polyclonal
      antibodies to putrescine, spermidine and spermine were obtained. However, these
      antibodies showed a variable degree of cross-reactivity to the polyamines not
      used for immunization. Two hybridoma cell lines were developed. The first,
      MPut88, selectively produces a Mab to putrescine, the second, MSpm/d88 produces a
      Mab which recognizes spermine and spermidine but does not react with putrescine.

PMID- 1995710
TI  - Presence of matrix-specific antibodies in affinity-purified polyclonal
      antibodies.
AB  - In general, antigen affinity columns made with commercially prepared activated
      affinity supports bind antibody specific for the coupled antigen. Nonetheless, in
      some cases affinity purification may yield antibodies to molecules other than the
      molecule of interest. In this report, we demonstrate such an occurrence: an
      antibody which adsorbs to an Affi-Prep 10 affinity matrix was found in the serum
      of sheep immunized against calmodulin. The contaminating antibody bound to cell
      nuclei and condensed chromosomes; the composition of the Affi-Prep 10 matrix
      suggests that the antibody may cross-react to the sugar-phosphate backbone of
      DNA. We were able to remove the contaminating antibody from the anti-calmodulin
      by passing the affinity-purified mixture over an antigen-free Affi-Prep 10
      column.

PMID- 1995711
TI  - Development of an ELISA to assess the potency of horse therapeutic antivenom
      against Thai cobra venom.
AB  - An ELISA for the quantitation of antibodies against Naja naja siamensis venom
      proteins has been developed for use as a possible replacement for the in vivo
      neutralization assay of antivenom potency. Comparison was made with three
      preparations of venom proteins as antigens of ELISA: these were the crude venom,
      a toxin fraction and the purified principle postsynaptic neurotoxin of the Thai
      cobra. Eight batches of horse monovalent therapeutic anti-cobra antivenom, one of
      which served as positive reference, were assayed by the ELISAs and also by the in
      vivo neutralization assay using mice. When crude venom, the toxin fraction and
      the pure neurotoxin were used as antigens in the ELISAs, the correlation
      coefficients between the ELISA antibody titers and in vivo neutralization of the
      antivenoms were 0.82 (P less than 0.005), 0.94 (P less than 0.001) and 0.95 (P
      less than 0.001), respectively. Thus, the ELISA which measures only the antibody
      against the principle toxin of the snake venom should be most suitable for use as
      an in vitro assay of antivenom potency. The ELISA should also be useful for
      potency assessment and standardization of antivenoms against other elapid snake
      venoms whose lethal components are small, poorly immunogenic peptides.

PMID- 1995712
TI  - Quantitation of cellular tubulin in microtubules and tubulin pools by a
      competitive ELISA.
AB  - A comprehensive method is described for isolating microtubules from cultured
      mammalian cells and quantitating the tubulin content of both the microtubules and
      total cellular tubulin pools with a competitive enzyme-linked immunosorbent assay
      (ELISA). The microtubule isolation procedure involves detergent lysis of cells in
      a microtubule stabilizing buffer, high speed centrifugation to collect the
      cytoskeletons, and subsequent solubilization of tubulin from microtubule
      containing pellets. The competitive immunoassay involves preincubating an anti
      tubulin monoclonal antibody with an unknown quantity of tubulin in cell extracts
      or solubilized microtubules to quantitatively reduce the antibody available to
      bind to a tubulin-coated microtiter plate. Binding of remaining antibody to the
      microtiter plate is measured spectrophotometrically using an alkaline phosphatase
      conjugated secondary antibody. Quantitation is accomplished by comparison with a
      known quantity of bovine brain tubulin.

PMID- 1995713
TI  - Heterologous enzyme immunoassay for the determination of free indole-3-acetic
      acid (IAA) using antibodies against ring-linked IAA.
AB  - A solid phase indirect enzyme immunoassay method for the plant growth substance
      indole-3-acetic acid (IAA) using polyclonal antibodies raised to IAA linked to
      rabbit serum albumin (RSA) is described. The sensitivity for IAA increased by
      more than three orders of magnitude as the number of IAA ligands on the coating
      antigen decreased. Further improvements in assay sensitivity were limited by the
      high affinity of the antibodies for the bridge group in the IAA conjugate.
      Substitution of the IAA in the coating antigen by either indole-3-propionic acid
      or indole-3-lactic acid reduced antibody recognition of the bridge group. The
      resulting heterologous assay compares favourably with existing homologous
      immunoassays for IAA in terms of sensitivity and specificity.

PMID- 1995714
TI  - One- and two-step non-competitive avidin-biotin immunoassays for monomeric and
      heterodimeric antigen.
AB  - In this study of one-step and two different two-step non-competitive avidin
      biotin assays (NABAs) were developed for the measurement of a monomeric antigen
      (lactoferrin, LF) using polyclonal antibodies and the detection of a
      heterodimeric antigen (lutropin. LH) using monoclonal antibodies. The assays were
      based on the use of performed complexes of biotinylated antibody and avidin
      peroxidase conjugate. The detection limits and intra-assay CVs of the one- and
      two-step NABAs were 0.1-0.5 mg/ml and 2.6-5.1% for LF, and 0.1-0.2 IU/l and 2.3
      3.7% for LH, respectively. The working range was 1-100 ng/ml for the LF assay and
      1-100 IU/l for the LH assay. A linear relationship with high correlation
      coefficients (0.979-0.992 for LF-NABAs: 0.949-0.990 for LH-NABAs) and good
      agreement was observed between the one- and two-step assays and the corresponding
      three-step NABAs used as reference methods. However, under stringent conditions
      the one-step assay for heterodimeric antigen was found to be sensitive to
      interference. The results indicate that it is possible to perform the multistep
      NABAs using convenient one- and two-step protocols. The one- and two-step assays
      also retained the advantages of the avidin-biotin system: rapidity and good
      sensitivity.

PMID- 1995715
TI  - Monoclonal antibodies against endometrial protein PP14 and their use for
      purification and radioimmunoassay of PP14.
AB  - Monoclonal antibodies against placental protein 14 (PP14) were generated in mice.
      One of these (code 105DH1F1) was used for the purification of PP14 from mid
      trimester amniotic fluid. The method is a simple one-step procedure, whereby
      monoclonal antibodies are bound to a solid phase and used for affinity
      immunoadsorption. 1.2 mg of PP14 was recovered from 25 ml of amniotic fluid.
      Using this purified PP14 and another monoclonal antibody (code 105AH7G3) a highly
      specific radioimmunoassay was developed. When the urine of pregnant women (7-10
      weeks gestation) was tested little PP14 could be found at the detection level of
      10 micrograms/l. The serum patterns of chorionic gonadotropin and PP14 were very
      similar in pregnancy. This study suggests that, unlike hCG, little PP14 is
      secreted into maternal urine. The purification method is gentle and allows quick
      purification of large amounts of PP14 for studies of its biological action(s).

PMID- 1995716
TI  - Methodological considerations when using nitrocellulose immunoblotting from
      polyacrylamide gels to study the mould allergens Aspergillus fumigatus and
      Alternaria alternata.
AB  - The effects of sample treatments, separation conditions, and the possible
      presence of antibody interference phenomena in sodium dodecyl sulphate
      polyacrylamide gel electrophoresis (SDS PAGE) followed by nitrocellulose
      immunoblotting (IB) were studied using allergens from Alternaria alternata
      (Alt.a.) and Aspergillus fumigatus (Asp.f.) as model systems. In order to obtain
      good resolution in the IB method the mould allergens were separated in gradient
      gels under dissociating conditions (SDSgPAGE) including sample treatment with
      boiling, SDS and 2-mercaptoethanol (ME). These treatments all reduced the IgE
      binding capacities of the Asp.f. and Alt.a. extracts studied. Nevertheless, a
      great variety of IgE-binding components were detected after IB, and this could
      probably be explained by refolding of allergens during the blotting procedure
      where SDS was partly removed. A comparison of IgG-enriched and IgG-reduced serum
      fractions in IB revealed small differences in the IgE-binding patterns suggesting
      that IgG interference is of minor importance in the system studied. The IB method
      must be individually optimized for each new allergen studied using well
      characterized sera, preferably monospecific for the major components. Taking
      these facts into consideration, the IB technique is a valuable complement to
      other methods in the study of mould allergens.

PMID- 1995717
TI  - Incidence of hairy cell leukemia, mycosis fungoides, and chronic lymphocytic
      leukemia in first known HTLV-II-endemic population.
AB  - Unlike human T cell leukemia-lymphoma virus type I (HTLV-I), HTLV-II has not been
      convincingly linked to a malignancy. In the first 10 months of serologic
      screening for HTLV-I/II among blood donors in New Mexico in 1988-1989, HTLV-I/II
      infection was found in 27 donors. HTLV-I/II infection was present in 1.0%-1.6% of
      American Indian and 0.16%-0.27% of Hispanic donors compared with 0.009%-0.06% of
      non-Hispanic white donors. HTLV-II was identified by DNA amplification in 12 of
      13 samples from Indian and Hispanic seropositive donors. Despite apparent endemic
      HTLV-II infection in these populations, New Mexico Tumor Registry data showed
      that the incidences of hairy cell leukemia, mycosis fungoides, and chronic
      lymphocytic leukemia were comparable among the three ethnic groups. A population
      with endemic HTLV-II infection has been identified, and there is no evidence of
      increased risk for these three malignancies in the endemic groups.

PMID- 1995719
TI  - Pattern of respiratory syncytial virus epidemics in Finland: two-year cycles with
      alternating prevalence of groups A and B.
AB  - Time-resolved fluoroimmunoassay with monoclonal antibodies distinguishing between
      respiratory syncytial virus (RSV) group A and B strains was used to analyze their
      prevalence in Finland during 1981-1990 among 3285 patients with laboratory
      diagnosis of RSV, most of them hospitalized. The group typing of antigens in 608
      RSV-positive nasopharyngeal aspirates showed a regular alternation of group
      prevalence, following the cyclic occurrence of the virus. Group A predominated in
      73%-90% of specimens from 1981-1982, 1985-1986, and 1989-1990, whereas group B
      predominated in 70%-100% of specimens from 1983-1984 and 1987-1988. The
      epidemiologic occurrence of verified reinfections in hospitalized children and
      the group typing results indicated that children greater than 6 months of age
      during the first infection were more resistant to severe reinfection with the
      homologous than with the heterologous group of virus. The study shows that group
      antigenic variation of RSV has a significant effect on the epidemiology of the
      virus.

PMID- 1995718
TI  - Human immunodeficiency virus (HIV-1) gp160-specific lymphocyte proliferative
      responses of mononuclear leukocytes from HIV-1 recombinant gp160 vaccine
      recipients.
AB  - The lymphocyte proliferative responses were studied of 12 volunteers enrolled in
      a phase I trial of a baculovirus-expressed recombinant human immunodeficiency
      virus type 1 (HIV-1) envelope glycoprotein (rgp160) vaccine. Six subjects
      received rgp160 and three subjects each received recombinant hepatitis B vaccine
      or placebo at 0, 1, and 6 months. rgp160 and a control preparation, baculovirus
      expressed recombinant HIV-1 p24, were used as in vitro antigens. At day 56, all
      rgp160 recipients had stimulation indexes (rgp160/rp24) greater than 3.0, and
      five of six had differences in counts per minute (cpm) greater than 1000.
      Stimulation indexes were less than 2.0 and cpm differences were less than 150 in
      all six who did not receive rgp160. Lymphocyte proliferative responses were first
      noted 2 weeks to 5 months before initial Western blot reactivity and persisted
      for greater than or equal to 540 days, even among subjects who lost detectable
      antibody. Thus, the HIV-1 rgp160 vaccine induces persistent cellular immune
      recognition as demonstrated by lymphocyte proliferation.

PMID- 1995720
TI  - Vaccination of cotton rats with a chimeric FG glycoprotein of human respiratory
      syncytial virus induces minimal pulmonary pathology on challenge.
AB  - The cotton rat model of human respiratory syncytial virus (RSV) infection was
      used to study the safety and efficacy of a chimeric FG glycoprotein that was
      expressed in insect cells using a baculovirus vector. Histologic and virologic
      examination of vaccinated rat lungs was done after challenge with RSV. When rats
      were challenged 1 month after vaccination, severe pulmonary inflammation
      characterized by both a mononuclear and polymorphonuclear cell infiltrate and 30%
      40% involvement of lung tissue was observed with a formalin-inactivated RSV
      vaccine. The FG glycoprotein induced minimal lung inflammation (involving 2%-5%
      of the lung), while negative controls had 1%-3% lung involvement. Two doses with
      as little as 20 ng of FG glycoprotein formulated in an aluminum hydroxide
      adjuvant completely protected the cotton rats from RSV challenge. Thus the
      chimeric FG glycoprotein is highly immunogenic and induces minimal pulmonary
      inflammation in the cotton rat model.

PMID- 1995722
TI  - Measles-associated diarrhea in hospitalized children in Lima, Peru: pathogenic
      agents and impact on growth.
AB  - Because the causes of measles-associated diarrhea are not well known, 0- to 5
      year-old children presenting to the hospital with measles-associated diarrhea
      (cases, n = 77) or acute diarrhea only (controls, n = 77) were compared. Growth
      and diarrheal morbidity were evaluated for 1 month after acute illness.
      Campylobacter jejuni was more frequently isolated from cases (31%) than controls
      (16%; P = .03). Rotavirus was absent in all cases versus 28% of controls (P less
      than .001). Incidence density for new episodes of diarrhea was significantly
      greater in cases (6.5 vs. 4.1; odds ratio, 1.6; confidence intervals, 1.09-2.34;
      P = .01), as was duration of episodes (3 vs. 2 days, P = .02). Both groups showed
      similar positive cumulative percentage weight gains throughout follow-up. These
      data support the theory of measles as a risk factor for developing diarrhea. The
      bacteriologic and virologic findings may reflect the immunologic response of the
      host to measles infection.

PMID- 1995721
TI  - A field study of the safety and efficacy of two candidate rotavirus vaccines in a
      Native American population.
AB  - A double-blind, randomized, placebo-controlled trial was conducted to evaluate
      the safety and efficacy of a rhesus rotavirus vaccine and RIT 4237, a bovine
      rotavirus vaccine, in a Navajo population. Infants aged 2-5 months were
      randomized to receive one dose of either 10(4) pfu of the rhesus rotavirus
      vaccine or 10(8) pfu of the RIT 4237 vaccine or placebo. Eleven (10.2%) of 108
      infants in the rhesus vaccine group, 11 (10.4%) of 106 in the RIT 4237 group, and
      9 (8.4%) of 107 in the placebo group experienced rotavirus diarrhea during the
      follow-up period of 17 months. Thus, in this population, neither vaccine was
      efficacious in preventing rotavirus diarrhea.

PMID- 1995723
TI  - Diffuse-adhering Escherichia coli (DAEC) as a putative cause of diarrhea in Mayan
      children in Mexico.
AB  - Diarrhea is a major cause of infantile morbidity and mortality in developing
      countries. A community-based, case control study was conducted in a southern
      Mexican Mayan village for 3 weeks during the peak diarrhea period to
      prospectively identify the infectious agents associated with childhood diarrheal
      disease. Several enteropathogens were isolated from stools of 34 of 58 cases,
      although none was significantly associated with diarrhea. For the 24 cases from
      which no enteropathogens were isolated, diffuse-adhering Escherichia coli (DAEC)
      strains were significantly associated with diarrheal disease (P less than .02;
      odds ratio = 6; 95% confidence limit, 1.08-99.0). DAEC were highly heterogeneous
      with respect to plasmid content and serotype. Three DNA probes designed to
      differentiate E. coli exhibiting localized, diffuse, or aggregative adherence
      were compared with results from a standard HeLa cell binding assay to assess the
      utility of these probes in the field. This study provides evidence for the
      potential pathogenic capacity of DAEC and underscores the variety of diarrheal
      agents operating within a community.

PMID- 1995724
TI  - Beta-lactam resistance mechanisms of methicillin-resistant Staphylococcus aureus.
AB  - In vitro and in vivo activity of amoxicillin and penicillin G alone or combined
      with a penicillinase inhibitor (clavulanate) were tested against five isogenic
      pairs of methicillin-resistant Staphylococcus aureus (MRSA) producing or not
      producing penicillinase. Loss of the penicillinase plasmid caused an eight times
      or greater reduction in the MICs of amoxicillin and penicillin G (from greater
      than or equal to 64 to 8 micrograms/ml), but not of the penicillinase-resistant
      drugs methicillin and cloxacillin (greater than or equal to 64 micrograms/ml).
      This difference in antibacterial effectiveness correlated with a more than 10
      times greater penicillin-binding protein 2a affinity of amoxicillin and
      penicillin G than of methicillin and a greater than or equal to 90% successful
      amoxicillin treatment of experimental endocarditis due to penicillinase-negative
      MRSA compared with cloxacillin, which was totally ineffective (P less than .001).
      Amoxicillin was also effective against penicillinase-producing parent MRSA,
      provided it was combined with clavulanate. Penicillinase-sensitive beta-lactam
      antibiotics plus penicillinase inhibitors might offer a rational alternative
      treatment for MRSA infections.

PMID- 1995725
TI  - Activation of in vitro proliferation of human T cells by a synthetic peptide of
      toxic shock syndrome toxin 1.
AB  - A 21-mer synthetic peptide (KGEKVDLNTKRTKKSQHTSEG), designated TSST-1(58-78), was
      constructed from the primary structure of the toxic shock syndrome toxin 1 (TSST
      1). The peptide reacted with a panel of neutralizing monoclonal antibodies (MAbs)
      to whole TSST-1 in solid-phase immunoassays. TSST-1(58-78) promoted the in vitro
      proliferation of human peripheral blood mononuclear cells (PBMC) in a dose
      dependent manner. Minimum dose required for stimulation (P less than or equal to
      .05 microM) was 0.75 microM peptide. This mitogenic effect was abrogated by
      incubation of the peptide with MAbs to whole TSST-1 before addition to PBMC. The
      ability of TSST-1(58-78) to stimulate the proliferation of highly purified
      resting human T cells was analyzed. Significant proliferation (P less than or
      equal to .01) was observed only in the presence of increasing populations of
      monocytes added to the cultures. Adherent human monocytes exposed to TSST-1(58
      78) released tumor necrosis factor. Thus, some of the immunoregulatory properties
      attributed to TSST-1 are demonstrated by the region of the toxin represented by
      the peptide TSST-1(58-78).

PMID- 1995726
TI  - Diagnosing Staphylococcus aureus endocarditis by detecting antibodies against S.
      aureus capsular polysaccharide types 5 and 8.
AB  - Consecutive serum samples from patients with Staphylococcus aureus endocarditis
      or septicemia or non-S. aureus endocarditis and febrile nonsepticemic controls
      were tested for antibodies against S. aureus capsular polysaccharide (CP) types 5
      and 8 by ELISA. The upper normal antibody levels were defined as the upper 99.5%
      confidence limits of the values from the febrile controls. All available patient
      isolates were tested for the presence of CP type 5 or 8 (85% of the isolates
      expressed either serotype), and all five patients with S. aureus endocarditis had
      positive antibody levels against the corresponding serotype within the first 10
      days of infection. Three other endocarditis patients lacked isolates for CP
      testing but two of these were positive. Positive antibody levels were found in 0
      of 28 septicemia patients, in 1 of 12 non-S. aureus endocarditis patients, and in
      3 of 37 febrile controls. Thus, testing for anti-CP 5 or 8 antibodies, especially
      together with CP serotyping of the patient's isolate, seems to provide important
      information in the differential diagnosis of endocarditis in patients with S.
      aureus septicemia.

PMID- 1995727
TI  - Isolation and composition of the extracellular slime made by coagulase-negative
      staphylococci in a chemically defined medium.
AB  - Slime isolated after growth of four strains of coagulase-negative staphylococci
      on chemically defined medium plus agar was rich in galactose. However, when
      sterile agar plates were extracted with saline, high-molecular-weight material
      with similar properties was obtained that also was galactose-rich. Most of the
      dry weight attributed to slime, and probably all the galactose, originated from
      agar. Slime isolated by gel and ion-exchange chromatography from liquid culture
      in the same medium contained glycerol phosphate, glucose (no galactose),
      glucosamine, alanine, uronate, an unidentified component, and protein. Separation
      of protein from carbohydrate was achieved by affinity chromatography.
      [14C]glucose in the medium labeled the carbohydrate polymer; [14C]amino acids
      chiefly labeled extracellular proteins. Slime from bacteria grown on medium
      solidified with silica gel or on dialysis membrane above an agar surface showed
      essentially the same composition and behavior after purification as the material
      isolated from liquid culture.

PMID- 1995728
TI  - Extremely high incidence of antibiotic resistance in clinical isolates of
      Streptococcus pneumoniae in Hungary.
AB  - An epidemiologic survey of antibiotic resistance among pneumococcal isolates
      collected during 1988 and 1989 in Hungary indicated that as many as 58% of all
      isolates and 70% of isolates from children were resistant to penicillin. These
      figures surpass even the highest values reported thus far for Spain and South
      Africa for the same period. Almost or more than 70% of the penicillin-resistant
      isolates were also resistant to tetracycline, erythromycin, and cotrimoxazole and
      approximately 30% to chloramphenicol. Intravenous administration of ampicillin
      (30 mg/kg) did not interfere with the growth in the cerebrospinal fluid of three
      resistant strains introduced into the rabbit model of experimental meningitis. No
      resistant strain showed beta-lactamase activity. A representative highly
      resistant strain contained altered penicillin-binding proteins (low penicillin
      affinities and abnormal molecular sizes) and was also resistant to the lytic and
      killing effects of penicillin.

PMID- 1995729
TI  - Immune responses to Bordetella pertussis infection and vaccination.
AB  - To assess antibody and cellular immune responses, 156 healthy children were
      immunized at approximately 18 months of age with acellular diphtheria-tetanus
      pertussis vaccine. Changes in antibody responses to filamentous hemagglutinin
      (FHA) and to pertussis toxin (PT) were similar in pattern, and antibody titers
      reached values equal to those from patients with convalescent-stage pertussis.
      The FHA-induced DNA synthesis in peripheral blood mononuclear cells was maximum
      at 4 weeks after the primary series, and these levels were equal to those of
      patients with pertussis. High amounts of PT-induced DNA synthesis were observed
      in both immunized and nonimmunized children; thus, PT seemed to act mainly as a
      nonspecific mitogen. Almost the same responses to several mitogens that activate
      different subsets of lymphocytes were observed in young infants compared with
      older children. Furthermore, young infants who had Bordetella pertussis infection
      responded by FHA stimulation almost as well as older children.

PMID- 1995730
TI  - Serologic diagnosis of human ehrlichiosis using two Ehrlichia canis isolates.
AB  - Ehrlichia canis or a closely related rickettsial organism has been implicated
      serologically and morphologically as the causative agent of human ehrlichiosis in
      the United States. Although E. canis has been serially propagated in primary
      canine monocytes, only a limited quantity of antigen is obtained by this method.
      A continuous canine macrophage cell line, DH82, supports the growth of a new
      isolate of E. canis established from the whole blood of a carrier dog in
      Oklahoma. Serologic comparison of the Oklahoma isolate in the continuous canine
      cell line with a Florida isolate in commercial antigen slides revealed 100%
      specificity and 87.5% sensitivity.

PMID- 1995731
TI  - Recombinant murine granulocyte-macrophage colony-stimulating factor augments
      neutrophil recovery and enhances resistance to infections in myelosuppressed
      mice.
AB  - The ability of recombinant murine granulocyte-macrophage colony-stimulating
      factor (rmGM-CSF) to protect myelosuppressed mice against lethal infections was
      evaluated. In mice myelosuppressed by cyclophosphamide, subcutaneously
      administered rmGM-CSF was a potent stimulus of granulopoiesis by increasing the
      number of GM-CSF-responsive precursor cells in bone marrow followed by a profound
      neutrophilia. Neutrophil recovery was augmented by rmGM-CSF in a dose-dependent
      manner at daily doses of 0.6-5.0 micrograms/mouse. In addition, rmGM-CSF
      increased the functional activity of circulating neutrophils at similar doses.
      When rmGM-CSF was administered to neutropenic mice before experimentally induced
      Pseudomonas aeruginosa, Staphylococcus aureus, or Candida albicans infections, it
      protected against these lethal infections, resulting in increased numbers of
      survivors. These data suggest that rmGM-CSF protects neutropenic mice from lethal
      infections, probably by augmenting neutrophil recovery after myelosuppression and
      activation of mature cells.

PMID- 1995733
TI  - Isolation and characterization of a new human microsporidian, Encephalitozoon
      hellem (n. sp.), from three AIDS patients with keratoconjunctivitis.
AB  - A new human microsporidian was isolated from cultures of Madin-Darby canine
      kidney cells incubated with conjunctival scrapings or corneal tissues from three
      AIDS patients with keratoconjunctivitis. The three isolates were morphologically
      similar to Encephalitozoon cuniculi. The spores averaged 1 x 1.5-2.0 microns, had
      six to eight polar filament coils, displayed monokaryotic nuclei, and possessed
      relatively thick endospores with irregularly shaped exospores. Organisms
      developed within a parasitophorous vacuole. By SDS-PAGE analysis, the three
      isolates appeared to be identical but were different from E. cuniculi. Identical
      banding patterns on Western blots of the three isolates were expressed by each
      patient's serum. By Western immunoblotting, murine antisera to E. cuniculi
      reacted to several antigens of the new AIDS-related microsporidian, whereas
      murine antisera bound weakly to Nosema corneum. The name Encephalitozoon hellem
      (n. sp.) is proposed to identify this new human microsporidian.

PMID- 1995732
TI  - Clinical disease, drug susceptibility, and biochemical patterns of the unnamed
      third biovariant complex of Mycobacterium fortuitum.
AB  - Previous studies of Mycobacterium fortuitum identified isolates that did not fit
      its two recognized biovariants. Eighty-five clinical isolates of this group, the
      "third biovariant complex", were evaluated. They represented 16% of 410 isolates
      of M. fortuitum submitted to a Texas laboratory and 22% of 45 isolates in
      Queensland, Australia. Most infections (76%) involved skin, soft tissue, or bone
      and occurred after metal puncture wounds or open fractures. Isolates differed
      from biovar fortuitum in resistance to pipemidic acid and use of mannitol and
      inositol as carbon sources. Two subgroups were present, and examples were
      deposited in the American Type Culture Collection. Isolates were resistant to
      doxycycline and one-third were resistant to cefoxitin. All were susceptible to
      amikacin, ciprofloxacin, sulfamethoxazole, and imipenem. Surgical debridement
      combined with drug therapy based on in vitro susceptibilities resulted in cures
      of cutaneous disease or osteomyelitis. DNA homology studies are needed to
      determine the taxonomic status of these organisms.

PMID- 1995735
TI  - Susceptibility to invasive Haemophilus influenzae type b disease and the
      immunoglobulin G2m(n) allotype.
AB  - There has been considerable controversy about the role of the immunoglobulin
      G2m(n) allotype and risk of invasive Haemophilus influenzae type b (Hib) disease.
      This allotype was studied in a large cohort of Finnish children (178) with
      invasive Hib disease. The G2m(n) allotype distribution was similar to that in the
      normal white Finnish population. No increased risk of Hib disease could be
      associated with the n-/n- genotype [i.e., lack of G2m(n) allotype]. Thus, the
      G2m(n) allotype does not seem to be a major determinant of susceptibility to Hib
      infection among white populations in industrialized countries.

PMID- 1995734
TI  - Postexposure prophylaxis with zidovudine suppresses human immunodeficiency virus
      type 1 infection in SCID-hu mice in a time-dependent manner.
AB  - Occupational exposure to the human immunodeficiency virus (HIV) has led to a low
      but finite incidence of infection among health care providers. In such
      circumstances, postexposure administration of 3'-azido-3'-deoxythymidine
      (zidovudine; AZT) might be beneficial. To test this possibility, the SCID-hu
      mouse (the immunodeficient C.B-17 scid/scid mouse engrafted with human
      hematolymphoid organs) was treated with AZT at different times after intravenous
      infection with a standard dose of HIV (known to infect 100% of animals). If given
      within 2 h, AZT suppressed infection in all animals; if given after 2 days, no
      suppression was observed. At least in some animals, an AZT-sensitive phase lasted
      for as long as 36 h. These data support the hypothesis that prompt administration
      of AZT might be efficacious in suppressing acute HIV infection in humans. Further
      studies in the SCID-hu mouse might provide insight into treatment protocols of
      even greater efficacy.

PMID- 1995736
TI  - Role of tolerance in cloxacillin treatment of experimental Staphylococcus aureus
      endocarditis.
AB  - The role of Staphylococcus aureus tolerance was investigated in endocarditis in
      rats. The efficacies of cloxacillin, gentamicin, and a combination of the two
      were compared for animals infected with a tolerant strain, its kill-sensitive
      variant, or a nonisogenic nontolerant strain of S. aureus. Cloxacillin was
      significantly less effective for treating the tolerant than for the nontolerant
      strains. The addition of gentamicin to cloxacillin reduced bacterial numbers in
      endocardial vegetations for the tolerant strain comparable to the reduction by
      cloxacillin alone for the nontolerant strains, but had no additional effect for
      the nontolerant strains. Isolates from animals infected with the tolerant or
      nontolerant strains during antibiotic treatment remained tolerant or nontolerant.
      These results show that the in vitro phenomenon of tolerance is relevant in vivo.

PMID- 1995737
TI  - Serotypes of respiratory isolates of Streptococcus pneumoniae compared with the
      capsular types included in the current pneumococcal vaccine.
AB  - The serotypes of 474 clinically significant Streptococcus pneumoniae respiratory
      isolates collected during a national surveillance study in 1987-1988 were
      compared to the capsular types included in the 23-valent pneumococcal
      polysaccharide vaccine licensed for use in the United States. Overall, 355
      isolates (74.9%) belonged to types included in the current vaccine, while another
      65 (13.7%) were types serologically related to vaccine types and likely to be
      protective by virtue of cross-reactivity. Relatively few isolates (9.1%) belonged
      to nonvaccine serotypes, and only 2.3% were nontypable. The mucoid serotype 3 was
      most frequent (13.1% of total), followed by 19F (9.3%), 23F (7.4%), 6B and 14
      (5.7% each), and 4 and 6A (5.5% each). The most frequent type not included in the
      vaccine was type 16 (2.1% of all isolates). Thus, nearly 89% of respiratory
      isolates included in this study were encompassed within the antigenic spectrum of
      the currently marketed pneumococcal vaccine.

PMID- 1995738
TI  - Effect of indomethacin on the pathophysiology of experimental meningitis in
      rabbits.
AB  - The effects of indomethacin on central nervous system abnormalities in rabbits
      with experimental pneumococcal meningitis were studied. As expected,
      prostaglandin E2 levels in cerebrospinal fluid were significantly lower in the
      indomethacin-treated group, indicating that the drug effectively reduced
      prostaglandin synthesis. Brain edema was markedly attenuated in the indomethacin
      treated group; however, cerebrospinal fluid white blood cell counts, lactate and
      protein concentrations, and intracisternal pressure were not significantly
      different between groups. It seems that indomethacin, while effective in reducing
      brain edema, does not significantly affect other important pathophysiologic
      alterations in experimental pneumococcal meningitis.

PMID- 1995739
TI  - Urinary phenolic glycolipid 1 in the diagnosis and management of leprosy.
AB  - A simplified assay to measure the phenolic glycolipid 1 (PGL-1) of Mycobacterium
      leprae in the urine was applied to the diagnosis of leprosy and the monitoring of
      antileprosy chemotherapy. One hundred seventy-nine previously untreated patients
      and 25 normal controls were tested. The specificity of the assay was 100%. There
      were no false-positive results. The sensitivity of the assay varied with the type
      of leprosy from 92% for lepromatous leprosy to 56% for borderline lepromatous and
      18% for borderline tuberculoid patients. After the onset of chemotherapy in
      lepromatous leprosy patients, there was often a transient increase of urinary PGL
      1, followed by a steady decline. Within 3 months of multiple drug therapy,
      urinary PGL-1 levels were reduced by 90%-99% and were often undetectable. This
      assay appears to have considerable potential for monitoring chemotherapy and
      detecting treatment failure and relapse in patients with Hansen's disease.

PMID- 1995740
TI  - Antiborrelial activity of serum from rats injected with the Lyme disease
      spirochete.
AB  - The functional properties of humoral factors generated in rats immunized against
      Borrelia burgdorferi were investigated. After Lewis strain rats were injected
      intraperitoneally with live B. burgdorferi or in the footpad with dead borreliae
      incorporated in complete Freund's adjuvant, they produced high-titered antisera.
      At a dilution of less than or equal to 1:10, sera from immunized or infected rats
      but not control sera inhibited growth of B. burgdorferi in vitro. Neutralization
      of growth of three different strains of B. burgdorferi by posttreatment sera was
      dose-dependent and was detected equally well by direct microscopic counts or by
      measuring incorporation of tritiated adenine into newly synthesized nucleic
      acids. These findings provide direct evidence that infection or immunization with
      the Lyme disease spirochete induces the formation of serum factors capable of
      preventing the growth of B. burgdorferi in vitro.

PMID- 1995741
TI  - Yersinia enterocolitica O:3: an emerging cause of pediatric gastroenteritis in
      the United States. The Yersinia enterocolitica Collaborative Study Group.
AB  - After an outbreak of Yersinia enterocolitica infections among black children in
      Atlanta, a seven-hospital study was conducted to determine the importance of this
      pathogen in other communities with large black populations. Of 4841 stool
      specimens from patients with gastroenteritis examined between November 1989 and
      January 1990, Y. enterocolitica, Shigella, Campylobacter, and Salmonella were
      identified in 38, 49, 60, and 98 specimens, respectively; 34 (92%) of 37 Y.
      enterocolitica isolates were serotype O:3. Of the 38 patients with yersiniosis,
      37 (97%) were children. Illnesses were clustered around the holidays, and 20
      (62%) of 32 patients had been exposed to raw pork intestines in the 2 weeks
      before onset. Exposure was significantly associated with illness in a case
      control study of eight patients identified at one hospital (P = .004). Infants
      less than or equal to 6 months old with yersiniosis were more likely to have
      immature-to-total neutrophil ratios greater than 0.50 than were infants of
      comparable age with salmonellosis (P = .02). Infrequently isolated in the past,
      Y. enterocolitica O:3 is emerging as an important enteric pathogen in this
      country, particularly among black children.

PMID- 1995743
TI  - Nosocomial Legionnaires' disease and use of medication nebulizers.
AB  - Guidelines for the prevention of nosocomial pneumonia specify that only sterile
      fluids should be used for aerosol therapy; however, this recommendation may not
      be uniformly followed. Thirteen patients with nosocomial pneumonia due to
      Legionella pneumophila serogroup 3 (Lp3) were identified at a community hospital
      in the period from 1984 through 1988; 12 patients (92%) had chronic obstructive
      pulmonary disease; and 9 patients (69%) died. An epidemiologic investigation
      suggested that the use of nebulizers to deliver medication was associated with
      acquiring legionnaires' disease. The hospital potable water system was
      contaminated with Lp3, and a survey indicated that tap water was commonly used to
      wash medication nebulizers. Lp3 in respirable-size droplets was isolated from
      aerosols generated by a nebulizer containing Lp3 at one-tenth the concentration
      found in the hospital potable water. These findings support the recommendation
      that only sterile fluids be used for filling or cleaning respiratory care
      equipment and suggest that this guideline is not universally followed.

PMID- 1995742
TI  - Preexposure of the peritoneum to live bacteria increases later mixed
      intraabdominal abscess formation and delays mortality.
AB  - Intraabdominal infections are a major source of morbidity and mortality for the
      trauma and postoperative patient. Transient peritoneal contamination with
      bacteria after either intentional or unintentional violation of the gut are
      common. The effect of this intermittent antigen exposure upon later formation of
      intraabdominal abscesses is unclear. Previous experiments by others have
      demonstrated that repeated exposure to Bacteroides fragilis capsular
      polysaccharide can induce a T lymphocyte-mediated immunity to subsequent
      induction of pure B. fragilis abscess formation. In a murine mixed intraabdominal
      abscess model, preexposure to live Escherichia coli, B. fragilis, or both
      increased the number of later abscesses and in some cases their bacterial
      composition. Further, immunization with E. coli alone increased late mortality
      without altering overall mortality. These data suggest that the alterations of
      immune function produced by live, transient bacteria upon subsequent mixed
      intraabdominal abscess induction result in fundamentally different consequences
      from those observed after specific polysaccharide antigen exposure and subsequent
      monomicrobial abscess induction.

PMID- 1995744
TI  - No detection of characteristic fungal protein elongation factor EF-3 in
      Pneumocystis carinii.
AB  - The taxonomic status of Pneumocystis carinii is uncertain, and P. carinii has
      been categorized both as a fungus and as a protozoan. Recent comparisons of RNA
      sequence homologies between P. carinii and several genera of fungi and protozoa
      suggest that P. carinii has closer affinities with the ascomycetes than with the
      protozoa. The translatory systems of the fungi, however, require three soluble
      protein factors for peptide chain elongation rather than the two necessary in
      other eukaryotic systems; to date the additional protein elongation factor (EF-3)
      appears to be unique to fungi. Western blot analysis of cell-free extracts of P.
      carinii, derived from rat, was done using a polyclonal antibody raised in rabbits
      to Saccharomyces cerevisiae EF-3. Anti-EF-3 cross-reacting material was detected
      only in lysates of Candida albicans and S. cerevisiae included as fungal
      controls; no cross reaction was detected in lysates of P. carinii, P. carinii
      infected rat lung, or a protozoan control (Trichomonas vaginalis).

PMID- 1995745
TI  - Toxic shock syndrome and staphylococcal infection.

PMID- 1995746
TI  - Experimental findings that prior infection with herpes simplex virus (HSV) type 1
      prevents subsequent infection with HSV type 2.

PMID- 1995747
TI  - Age-related prevalence of serum antibody to respiratory syncytial virus in
      Ecuadorian and German children.

PMID- 1995748
TI  - Lyme disease in South America?

PMID- 1995750
TI  - Cost consciousness.

PMID- 1995749
TI  - Application of the microcapsule agglutination test to serologic studies of an
      early stage of Lyme disease in Japan.

PMID- 1995751
TI  - Release of patient medical records.

PMID- 1995752
TI  - HLA type and the genetic risk for type 1 diabetes mellitus.
AB  - One hundred twenty-nine type 1 diabetic children and 176 non-diabetic siblings
      from the Louisville referral area were HLA typed by microlymphocytotoxicity
      technique. DR antigen frequencies were compared to frequencies for the Southeast
      USA population. Frequencies of DR3 and DR4 were significantly increased in both
      the diabetics and their unaffected siblings relative to the general population
      and DR2 was decreased. Forty-six percent of diabetic children possessed both DR3
      and DR4 antigens while only 7% had neither. The findings are consistent with
      those in other geographical areas and give strong support to the role of DR3 and
      DR4 antigens as markers for diabetes susceptibility genes.

PMID- 1995753
TI  - Pneumothorax: an unusual presentation of primary bronchogenic neoplasm.
AB  - We report the occurrence of spontaneous pneumothorax as the initial pulmonary
      event in a patient subsequently found to have a primary adenocarcinoma of the
      ipsilateral lung. A review of the literature regarding this rare presenting
      feature of bronchogenic neoplasm is provided.

PMID- 1995754
TI  - Theophylline toxicity.

PMID- 1995755
TI  - Thoughts on paperwork. The use of your signature.

PMID- 1995756
TI  - Breakthroughs in ascites: effects on bottom lines.

PMID- 1995757
TI  - AZT--does it prevent occurrence of salmonelloses in AIDS patients?

PMID- 1995758
TI  - Changes in plasma high density lipoprotein cholesterol and phospholipid in acute
      viral hepatitis and cholestatic jaundice.
AB  - Forty-four male and female subjects aged 22-57 years were studied. Thirteen
      patients had acute viral hepatitis, and eleven patients had cholestatic jaundice
      due to carcinoma of the head of the pancreas. Twenty healthy volunteers who
      served as controls were also included. In hepatitis patients, the mean plasma
      levels of total cholesterol (TC) and the high density lipoprotein (HDL)
      phospholipid/phospholipid (HDLPL/PL) ratio were reduced, and HDL-cholesterol
      (HDLC), HDL-phospholipid (HDLPL) and the phospholipid/total cholesterol (PL/TC)
      ratio were normal, while total phospholipid (PL) levels and the HDLC/TC ratio
      were significantly increased compared to the control values. In patients with
      cholestatic jaundice the mean plasma total cholesterol, phospholipid and HDLC
      levels were elevated, and HDLPL/PL, HDLPL, HDLC/TC and PL/TC remained normal
      compared to the control values. A comparison within the patient groups showed
      that plasma TC, PL and HDLC levels were significantly increased in cholestatic
      jaundice when compared with the corresponding levels in hepatitis patients. The
      mean plasma levels of HDLPL, HDLC/TC and PL/TC did not show any significant
      variation within the patient groups. Alkaline phosphatase (ALP) correlated
      positively with TC, and total protein correlated negatively with TC and HDLPL,
      while albumin correlated negatively with TC, HDLC and HDLPL in cholestatic
      jaundice. Alanine amino-transferase (ALAT) also correlated positively with PL in
      cholestatic jaundice, while albumin correlated positively with TC in hepatitis.
      The results suggest that lipoproteins might be metabolized differently in these
      two forms of cholestasis.

PMID- 1995759
TI  - Sudden death and sleeping history among Finnish men.
AB  - An autopsy was performed in 460 consecutive cases of sudden death among 35- to 76
      year-old men. The closest cohabiting individual known to each decreased subject
      was interviewed. Snoring history was obtained in 321 of the 371 interviews. In 86
      cases there was a history of 'habitual' (almost always or always) snoring, and 88
      men snored 'often'. The mean age of subjects was 55.4 years. The mean body mass
      index (BMI) was 26.3 kg m-2. Among the obese snorers (n = 82), apnoeas had been
      observed 'occasionally', 'often', or 'habitually' in 49 cases. Death was
      classified as cardiovascular in 186 (40.4%) cases. Cardiovascular cause of death
      was more common among those who snored habitually or often than among those who
      snored occasionally or never (P less than 0.05). 'Habitual' snorers died more
      often while sleeping (P less than 0.05). Habitual snoring was found to be a risk
      factor for morning death (P less than 0.01). The possibility of obstructive sleep
      apnoea as a cause of sudden death should at least be considered if the decreased
      is known to have been a habitual snorer.

PMID- 1995760
TI  - Drugs and femoral neck fracture: a case-control study.
AB  - Two hundred consecutive patients with femoral neck fractures (FNF) and 200
      controls matched by age, sex, nursing home residency and number of admissions
      within the last 2 years, were interviewed about recent drug use. The matching
      criteria were chosen to achieve case and control groups that were comparable with
      regard to overall physical disability. Thus a preliminary study had shown FNF to
      be strongly associated with nursing home residency and to be correlated with the
      number of recent hospital admissions. FNF was found to be negatively associated
      with use of coronary drugs (OR = 0.27; 95% CI = 0.11-0.70) and positively
      associated with drug use in general (OR = 2.00; 95% CI = 1.04-3.05). The OR for
      the various classes of psychotropic drugs was consistently greater than 1.,
      although this was not statistically significant. An inherent problem in
      interpreting such findings is that underlying disease may predispose the subject
      to both FNF and drug use, thus creating a non-causal relationship.

PMID- 1995761
TI  - Combined zidovudine and interferon-alpha treatment in patients with AIDS
      associated Kaposi's sarcoma.
AB  - The effectiveness of addition of interferon-alpha (IFN-alpha) to zidovudine in
      patients with AIDS-associated Kaposi's sarcoma was assessed in a non-randomized,
      phase II clinical trial. Twenty-one patients were treated with oral zidovudine
      (600 mg daily) and IFN-alpha was increased to 18 MU daily for another 4 weeks.
      Only one of the 20 evaluable patients achieved a partial response at 8 weeks,
      that lasted for 3 months. Despite IFN-alpha dose escalation in six patients, no
      further responses were seen. While myelotoxicity was mild, fatigue was the dose
      limiting side-effect that prevented dose escalation in seven eligible patients.
      The combined treatment did not result in a decrease in HIV-Ag. In summary, our
      results indicate that the addition of IFN-alpha to zidovudine in patients with
      AIDS-associated Kaposi's sarcoma is not an efficacious treatment.

PMID- 1995762
TI  - A form of familial hypobetalipoproteinaemia not due to a mutation in the
      apolipoprotein B gene.
AB  - Familial hypobetalipoproteinaemia (FHBL) is a dominant disorder of lipoprotein
      metabolism characterized by levels of apolipoprotein B-carrying lipoproteins
      (VLDL, IDL and LDL) which are 50% of the normal levels in the heterozygotes and
      almost absent in the homozygotes. Several reports have recently shown that the
      underlying defect in FHBL involves different mutations in the apo B gene which
      lead to reduced levels of apo B mRNA or to the production of truncated forms of
      apo B having either a lower synthetic rate or a higher catabolic rate than normal
      apo B. We here present a three-generation family with several FHBL members in
      which the linkage analysis shows absence of co-segregation between apo B gene
      alleles and the hypocholesterolaemic phenotype. We conclude that a dominantly
      transmitted mutation in a gene other than that for apo B is responsible for the
      low plasma cholesterol levels.

PMID- 1995763
TI  - Serum erythropoietin levels in the anaemia of chronic disorders.
AB  - Serum erythropoietin (S-EPO) levels were measured in 50 patients with anaemia of
      chronic disorders (ACD), classified into three groups according to their
      aetiology: inflammatory (n = 20), infectious (n = 15) and neoplastic (n = 15).
      The inflammatory group showed a higher mean S-EPO level (mean value +/- SEM, 69
      +/- 11 mU ml-1) than the neoplastic (43 +/- 5 mU ml-1; P less than 0.05) and
      infectious groups (27 +/- 4 mU ml-1; P less than 0.01). The S-EPO level in the
      inflammatory group also differed from that of 32 healthy controls (36 +/- 3 mU ml
      1; P less than 0.05). Fourteen patients with added iron deficiency (12 subjects
      from the inflammatory group) showed the highest S-EPO concentration (72 +/- 17 mU
      ml-1). Conversely, S-EPO levels were lower in febrile subjects (12 patients with
      infection and five with malignancy) than in non-febrile patients (28 +/- 4 mU ml
      1 vs. 55 +/- 7 mU ml-1; P less than 0.01). In the infectious group, the logarithm
      of S-EPO correlated directly with the haemoglobin and haematocrit values. We
      conclude that differences in S-EPO concentration in ACD may be further related to
      the patient's iron stores and temperature. A decrease in EPO production may
      contribute to the pathogenesis of ACD secondary to infection.

PMID- 1995764
TI  - Pancreatic autoantibodies and pancreatic function in Sjogren's syndrome.
AB  - Pancreatic autoantibodies were determined in 49 patients with Sjogren's syndrome
      and related to functional parameters. Pancreatic duct autoantibodies (PDA) were
      detected in the sera of three patients, and all showed abnormal exocrine
      pancreatic function. Islet cell antibodies (ICA) were not detected in the sera of
      the 49 patients, including two individuals with diabetes mellitus. In conclusion,
      PDA occur in patients with Sjogren's syndrome, and may be associated with
      exocrine pancreatic dysfunction.

PMID- 1995765
TI  - Effects of cigarette smoking on thyroid function and the prevalence of goitre,
      thyrotoxicosis and autoimmune thyroiditis.
AB  - The effect of smoking habits on thyroid function and the prevalence of thyroid
      diseases was studied in two birth cohorts (1928 and 1941) of men and women. A
      total of 1555 individuals (836 men and 719 women) were smokers. 1048 individuals
      (604 men and 444 women) were ex-smokers and 1497 individuals (560 men and 937
      women) were non-smokers. The serum thyrotropin (TSH) concentration was
      significantly lower in smokers than in ex-smokers and non-smokers (P = 0.05 and P
      = 0.001, respectively). Smoking habits did not affect the serum triiodothyronine
      (T3) concentrations. The prevalence of non-toxic goitre and toxic diffuse goitre
      was significantly higher in smoking women than in non-smoking women (P = 0.005
      and P = 0.04, respectively). Thiocyanate may be the goitrogenic factor
      responsible for the increased prevalence of non-toxic goitre. The cause of the
      increased prevalence of toxic diffuse goitre is less obvious. Hypothetically, an
      increase in sympathetic activity in smokers may promote the development of
      thyrotoxicosis in predisposed individuals, but immunological disturbances caused
      by smoking are another possibility.

PMID- 1995766
TI  - Prophylactic effect of self-administered pump-driven subcutaneous IgG infusion in
      patients with antibody deficiency: a triple-blind cross-over study comparing P
      IgG levels of 3 g l-1 versus 6 g l-1.
AB  - Eight adult patients with hypoimmunoglobulinaemia were randomly allocated to
      initiation of low- or high-level IgG-substitution. IgG was administered
      subcutaneously, at 50 or 150 mg ml-1, 20 ml per infusion, by means of a pocket
      portable electric infusion pump. Infusions were given 2 to 4 times weekly for 24
      months, with a change of dose regimen after 12 months. The desired plasma IgG
      levels were reached after a mean lag phase of 3 months (range 1-5 months). The
      median (and ranges) of the individual mean plasma IgG levels during the ensuing 9
      month periods were as follows: high-level period, 6.5 g l-1 (range 6.2-7.8 g l
      1); low-level period, 3.2 g l-1 (range 3.0-4.0 g l-1). During the high-level
      period, compared to the low-level period, there was a significant decrease in the
      following parameters: 'days in bed at home', 'days missed work' and 'days with
      fever'. No serious side-effects were observed. It is concluded that a plasma IgG
      concentration of 6 g l-1 can readily be achieved by subcutaneous IgG
      substitution, and the prophylactic effect is superior to that obtained with a
      plasma IgG concentration of 3 g l-1.

PMID- 1995767
TI  - Platelet fatty acids and function in two distinct regions of Belgium:
      relationship to age and dietary habits.
AB  - We compared the dietary habits, fatty acid composition of plasma and platelet
      phospholipids, and platelet function in two groups of healthy Belgian male
      subjects, known to differ in their mortality rate from coronary heart disease
      (CHD). In the Walloon subjects, there was a larger intake of saturated and a
      lower intake of (n-6) polyunsaturated fats, confirmed by the fatty acid
      composition of plasma and platelet phospholipids. While plasma HDL and total
      cholesterol were similar in the present samples of the two communities, platelet
      aggregation to epinephrine was significantly higher in the Walloon subjects. When
      the two populations were divided into younger (28-54 years) and older (55-73
      years) age groups, the older Walloon subjects exhibited platelet hyper
      aggregability to most of the agonists, compared to the other three groups. In
      addition to dietary fats, alcohol and smoking habits, age was an important
      determinant of platelet phospholipid fatty acids and platelet reactivity. The
      present results reinforce those of previous studies, indicating that platelet
      behaviour is significantly affected by the main risk factors for CHD.

PMID- 1995768
TI  - High cardiac output as a paraneoplastic syndrome.
AB  - A high cardiac output (17 1 min-1) was recorded in a young man suffering from
      lymphoplasmatocytotic lymphoma. The evolution of the blood disease was
      characterized by two relapses, during which clinical signs of heart failure were
      prominent but resolved with efficient blood chemotherapy. The known aetiologies
      of high cardiac output were excluded. The complete normalization of the cardiac
      parameters with blood remission suggests that the high cardiac output represented
      an unusual paraneoplastic syndrome, the pathogenesis of which still remains
      unknown, although several hypotheses were tested.

PMID- 1995769
TI  - Hypoglycaemic episodes during intensified insulin treatment: increased frequency
      but no effect on cognitive function.
AB  - Ninety-seven patients with insulin dependent diabetes mellitus (IDDM) were
      randomized to intensified conventional treatment (ICT, n = 44) or regular
      treatment (RT, n = 53). The mean HbA1c level (+/- SEM) was reduced from 9.5 +/-
      0.2% to 7.4 +/- 0.1% in the ICT group (P less than 0.001), and from 9.4 +/- 0.2%
      to 9.0 +/- 0.2% (P less than 0.01) in the RT group. The difference between the
      groups was significant (P less than 0.001). During a period of 3 years, 57% of
      the ICT patients (95% confidence interval 44-73%) and 23% of the RT patients (95%
      CI, 11-34%) (P less than 0.001) had at least one episode of serious
      hypoglycaemia, with the need for third-party assistance or resulting in coma.
      Eighteen of the 32 ICT patients who initially had adrenergic symptoms during
      hypoglycaemia changed to predominantly neuroglycopenic symptoms. This was the
      case with only 8 of 38 RT patients (P less than 0.01). The change in symptoms was
      related to the increased frequency of serious hypoglycaemia, but neither symptoms
      nor frequency of hypoglycaemia bor any relationship to insulin dose, body mass
      index, duration of diabetes or autonomic nerve function. The results of several
      neuropsychological tests did not differ between the groups at baseline, and did
      not change during the study. There were no signs of deteriorating cognitive
      function in the patients with serious hypoglycaemic episodes.

PMID- 1995770
TI  - Potential role of insulin in the clearance of remnant lipoproteins in
      dysbetalipoproteinaemia.
AB  - Dysbetalipoproteinaemia is a genetic disorder characterized by accumulation of
      lipoprotein remnant particles in the plasma, accelerated atherosclerosis, and the
      abnormal apoprotein E2. Uncontrolled diabetes mellitus can aggravate the
      hyperlipidaemia associated with this disorder, presumably by increasing
      triglyceride synthesis and reducing very low density lipoprotein catabolism by
      lipoprotein lipase. This report documents the gradual amelioration of
      dysbetalipoproteinaemia in uncontrolled diabetes mellitus following therapy with
      exogenous insulin alone. Although the beneficial effects of insulin therapy in
      this patient may include inhibition of triglyceride synthesis and improved
      triglyceride catabolism, we propose that insulin may also stimulate clearance of
      atherogenic remnant lipoprotein particles.

PMID- 1995771
TI  - Meta-meta-analysis: unanswered questions about aggregating data.

PMID- 1995772
TI  - The intrauterine device and pelvic inflammatory disease: the Women's Health Study
      reanalyzed.
AB  - The Women's Health Study (WHS) was a large, widely accepted and influential case
      control study of the relationship between the use of intrauterine contraceptive
      devices (IUDs) and pelvic inflammatory disease (PID). The data were collected at
      16 hospitals in 9 cities across the U.S.A. from October 1976 through August 1978.
      The first paper on this research was published in 1981 and concluded that IUDs
      increase the risk of PID. The report cited an estimated RR (relative risk) of PID
      for current IUD users vs nonIUD users of 1.6 with a 95% confidence interval of
      (1.4, 1.9). However, careful examination of the report reveals that the data
      support conclusions antithetical to those at which the author arrived. When the
      second report on the WHS was published in 1983, it was anticipated that many of
      the shortcomings of the first report would be corrected, but they were not. In
      1983 we undertook a complete reanalysis of the same WHS data using more
      appropriate criteria and the results were compared to the first two published
      reports. The reanalysis revealed an RR of 1.02 (0.86, 1.21) for current IUD users
      compared to noncontraceptors. The conclusion of the WHS should have been that
      IUDs do not increase the risk of PID.

PMID- 1995773
TI  - Response to "The intrauterine device and pelvic inflammatory disease: the Women's
      Health Study reanalyzed".

PMID- 1995774
TI  - Meta-analysis in epidemiology, with special reference to studies of the
      association between exposure to environmental tobacco smoke and lung cancer: a
      critique.
AB  - Meta-analysis, a set of statistical tools for combining and integrating the
      results of independent studies of a given scientific issue, can be useful when
      the stringent conditions under which such integration is valid are met. In this
      report we point out the difficulties in obtaining sound meta-analyses of either
      controlled clinical trials or epidemiological studies. We demonstrate that
      hastily or improperly designed meta-analyses can lead to results that may not be
      scientifically valid. We note that much care is typically taken when meta
      analysis is applied to the results of clinical trials. The Food and Drug
      Administration, for example, requires strict adherence to the principles we
      discuss in this paper before it allows a drug's sponsor to use a meta-analysis of
      separate clinical studies in support of a New Drug Application. Such care does
      not always carry over to epidemiological studies, as demonstrated by the 1986
      report of the National Research Council concerning the purported association
      between exposure to environmental tobacco smoke and the risk of lung cancer. On
      the basis of a meta-analysis of 13 studies, 10 of which were retrospective and
      the remaining 3 prospective in nature, the Council concluded that non-smokers who
      are exposed to environmental tobacco smoke are at greater risk of acquiring lung
      cancer than non-smokers not so exposed. In our opinion, this conclusion in
      unwarranted given the poor quality of the studies on which it is based.

PMID- 1995776
TI  - The numbers game.

PMID- 1995775
TI  - Regional obesity and risk of cardiovascular disease; the Framingham Study.
AB  - Risk of cardiovascular events was determined over 24 years of surveillance in
      relation to general adiposity reflected by relative weight and by regional
      obesity estimated by skinfolds and waist girth per inch of height. Upper quintile
      values of relative weight, subscapular skinfolds and waist girth were each
      associated with increased risks of cardiovascular disease in both sexes. Risk of
      total cardiovascular events increased with the degree of regional, central or
      abdominal obesity. Mortality from cardiovascular disease was also increased.
      Increased relative weight and central obesity were both associated with increased
      risk factors including cholesterol, blood pressure, glucose and uric acid.
      Changes in weight were mirrored by changes in risk factors with linear trends
      over a 15 lb range of weight fluctuations. Subscapular skinfold and the ratio of
      subscapular-to-triceps skinfold, measures of central obesity, were in either sex
      also associated with an increased probability of coronary attacks in particular.
      The subscapular skinfold contributed to CHD risk independent of body mass index
      (BMI). Multivariate analyses taking all the risk factors into account indicate an
      independent effect of abdominal obesity on stroke, cardiac failure and
      cardiovascular and all-cause mortality in men. In women, only the subscapular-to
      triceps skinfold ratio independently contributes to CHD, cardiovascular and all
      cause mortality. Regional obesity appears to be an independent contributor to
      cardiovascular disease at a given level of general adiposity, its effect only
      partially mediated through promotion of other known risk factors. These data
      suggest that cardiovascular disease is as closely linked to abdominal as to
      general adiposity.

PMID- 1995777
TI  - Design versus directionality.

PMID- 1995778
TI  - Clinical reality, binary models, babies and bath water.

PMID- 1995779
TI  - Community Health Accreditation Program.

PMID- 1995780
TI  - Identification of stress buffers in school-age children.
AB  - Dealing with stress has become an important issue in health education in
      community settings. With increasing demands and changes in the daily lives of
      families, helping children to deal with stress has become increasingly more
      significant in community health nursing. Nurses who want to mediate effects of
      stress in children need more information about stress buffers in the daily lives
      of children. This study attempted to identify and describe stress buffers as
      actually experienced by school-age children. Qualitative data were drawn from 32
      well children, aged 8 through 11 years, by completion of daily semistructured
      journals over a period of 6 weeks. Diaries produced 764 stress buffer responses.
      All data were subjected to content analysis. Sixteen categories among four
      general themes of intrapsychic comfort, physical-social activities, social
      support, and physical comfort emerged, beginning a taxonomy of stress buffers as
      perceived by children. Interesting differences between boys and girls were
      identified, with implications for research and community nursing practice.

PMID- 1995781
TI  - Program evaluation application of a comprehensive model for a community-based
      respite program.

PMID- 1995782
TI  - The use of home-based computers to support persons living with AIDS/ARC.
AB  - Care of the patient at home challenges nurses with both the quantity and
      diversity of services required. New technologies such as computer networks may
      provide mechanisms to relieve the burden on traditional services, while opening
      new ways to meet the unique needs of home-based patients in a timely and
      effective manner. Capitalizing on an existing, free, public-access computer
      network, we developed the ComputerLink, a computer network designed to provide
      home-care support to persons living with acquired immune deficiency syndrome
      (AIDS) and AIDS-related complex (ARC) in the community. In the pilot study
      presented here, we demonstrate the feasibility of using home-based computer
      networks to provide information, communication, and decision assistance to
      persons living with AIDS (PLWA). The success experienced with this particular
      group of patients provides sufficient encouragement to further test this
      intervention with PLWAs and to extent this nursing intervention to other groups
      of community-based patients.

PMID- 1995783
TI  - Cultural themes in health-care decision making among Cambodian refugee women.
AB  - The Cambodians are adapting to the American ways while still holding firmly to
      their culture. Such cultural identity provides security and a sense of
      equilibrium. With the Cambodian patient, providing culturally sensitive nursing
      care centers on supporting the concept of equilibrium. In this endeavor, the
      nurse plays multiple roles advocate, culture broker, educator, and friend.

PMID- 1995784
TI  - Stress related to family change among Vietnamese refugees.
AB  - Because life changes have been known to have consequences for emotional and
      physical well-being, this study demonstrates the need for community health nurses
      (CHNs) to assess structural and functional changes in Vietnamese refugee spousal
      relations as possible sources of stress following resettlement. The purpose of
      this study was to identify changes in the structural and functional dimensions of
      family life and assess their impact on spousal relations. The major variables
      considered in effecting change in spousal interactions were relocation, exposure
      to more liberal attitudes toward gender equality in the United States, and wife
      employment. Spousal power differentials and affectivity were used as measures of
      change. Intensive interviews, using a semistructured interview guide, were
      conducted with 30 Vietnamese refugee women; the sample was nonrandom and cross
      sectional. Information was collected on sociodemographic characteristics and pre-
      and postresettlement spousal relations. Wife employment, associated with
      proficiency in English and longer length of residence in the U.S., was found to
      promote more egalitarian spousal relations and greater spousal affectivity. When
      wives were not employed, they tended to describe an increase in affectivity
      without an appreciable decrease in spousal power differentials. This effect was
      enhanced by isolation within the host society as a result of limited English
      skills, unemployment, and a shorter length of residence.

PMID- 1995785
TI  - Effect of increasing the dietary (n-3) to (n-6) polyunsaturated fatty acid ratio
      on murine liver and peritoneal cell fatty acids and eicosanoid formation.
AB  - An incremental increase in the dietary (n-3):(n-6) polyunsaturated fatty acid
      (PUFA) ratio from 0 to 1.93 in diets containing 15% fat (wt/wt) decreased the
      total (n-6) PUFA content of phospholipids of the liver and peritoneal cells
      (macrophage) in mice from 43.1 and 33.6 mol/100 mol to 16.0 and 12.3 mol/100 mol
      with a concomitant increase of 27.6 and 16.1 mol/100 mol in (n-3) PUFA,
      respectively. Consumption of (n-3) PUFA increased hepatic (n-3) PUFA levels
      without changing total PUFA (46.35 vs. 46.87 mol/100 mol), whereas macrophage
      PUFA levels were decreased. The synthesis of sulfidopeptide leukotrienes (SP-LT)
      (LTC4 and LTE4) was progressively reduced by increasing dietary (n-3) PUFA, i.e.,
      there was a reduction of 76% in mice fed a diet containing a (n-3):(n-6) PUFA
      ratio of 1.93 compared with the control diet. The 5-series SP-LT (LTC5 and LTF5)
      were produced in all animals consuming (n-3) PUFA and accounted for 62% of all SP
      LT synthesized in mice fed the diet containing a 1.93 (n-3):(n-6) PUFA ratio.
      Synthesis of 6-keto-prostaglandin F1 alpha decreased 81% in mice fed a diet
      containing a (n-3):(n-6) PUFA ratio of 1.93 whereas prostaglandin E2 synthesis
      decreased 44% in mice fed diets with (n-3):(n-6) ratios ranging from 0.41 to
      1.93.

PMID- 1995786
TI  - The effects of fish oil on triglycerides, cholesterol, fibrinogen and
      malondialdehyde in humans supplemented with vitamin E.
AB  - The effects of fish oils supplemented with 0.3 IU/g and 1.5 IU/g of vitamin E
      were compared in a double-blind, cross-over study. Twelve healthy volunteers were
      given 30 mL/day of either oil for 3 wk. Intake of the vitamin E-rich fish oil
      resulted in a marked decrease in serum triglycerides (48%) and in fibrinogen
      (11%). After administration of the low vitamin E-containing oil there was a
      considerably smaller reduction of serum triglycerides and no significant
      reduction of fibrinogen. Both oils caused an increase in high density lipoprotein
      cholesterol and a decrease in the atherogenic index, but neither oil altered the
      total cholesterol level. Serum vitamin E was decreased by 9% and plasma
      malondialdehyde was increased by 122% after intake of the low vitamin E
      containing oil, but both remained normal after intake of the other oil. The
      effect of vitamin E may be due to inhibition of fatty acid peroxidation with less
      formation of malondialdehyde and a larger amount of active (n-3) fatty acids in
      their sites of action in the liver, resulting in a greater decrease in the
      synthesis of triglycerides and fibrinogen.

PMID- 1995787
TI  - Depletion and repletion kinetics of vitamin C in humans.
AB  - Depletion and repletion profiles of vitamin C were determined in young and
      elderly males and females. Plasma vitamin C concentrations were determined upon
      entry into the study, once each week during a 5-wk period of dietary restriction
      (10 mg/day) of the vitamin and twice each week during a 2.5-wk period of
      supplementation with 500 mg/d. The rate constant (K) and the half-life of the
      depletion phase (t1/2) were determined. Other values calculated included the mean
      plasma vitamin C concentration in the four subject groups at entry, depleted and
      supplemented states of vitamin C nutriture. A t test indicated that none of the
      calculated values differed due to age. In contrast, K was significantly smaller
      in men, resulting in a longer t1/2. The entry and depleted plasma vitamin C
      concentrations did not differ due to gender whereas repleted plasma vitamin C
      concentrations were higher in women than in men. Data analysis indicated that
      plasma depletion of vitamin C is a first-order process. In addition, t1/2 was
      inversely related to entry vitamin C levels at concentrations below approximately
      85 mumol/L whereas above this concentration t1/2 was approximately constant and
      averaged 14.2 d. This implies that a conservation effect may be operative at low
      plasma vitamin C concentrations.

PMID- 1995788
TI  - Bioavailability of pyridoxine-5'-beta-D-glucoside determined in humans by stable
      isotopic methods.
AB  - Stable-isotopic methods were employed to evaluate the utilization of dietary
      pyridoxine-5'-beta-D-glucoside (PN-glucoside), a major form of vitamin B-6 in
      plant-derived foods, as a source of available vitamin B-6 for adult men (20-35 y
      old, n = 5). Deuterium-labeled forms of free pyridoxine (PN) and PN-glucoside
      were compared using the urinary excretion of labeled forms of the vitamin B-6
      metabolite 4-pyridoxic acid as the main index of absorption and metabolism. When
      comparing orally administered, isotopically labeled PN and PN-glucoside in
      separate groups of subjects, similar bioavailability was observed although within
      group variability was high. A dual-label study designed to examine the
      bioavailability of these compounds when administered simultaneously indicated
      that the utilization of deuterated PN-glucoside was 58 +/- 13% (mean +/- SEM)
      relative to that of deuterated PN. PN-glucoside was detected in all urine
      samples, which provided additional evidence of incomplete metabolic utilization.
      In contrast, intravenously administered PN-glucoside underwent approximately half
      the metabolic utilization of oral PN-glucoside. These studies indicate that the
      bioavailability of dietary PN-glucoside, although incomplete, is substantially
      greater in humans than previously found in rats. In addition, the difference
      between oral and intravenous routes suggests a role of beta-glucosidase(s) of the
      intestinal mucosa, microflora, or both in the release of free PN from dietary PN
      glucoside.

PMID- 1995789
TI  - Effect of dietary silicon on growth and skeletal development in chickens.
AB  - Experiments were conducted to determine the effect of supplementary dietary
      silicon on weight gain, feed efficiency, percent tibia bone ash and on the
      development of tibial dyschondroplasia in broiler chickens. Experiments 1 and 2
      were conducted with casein/gelatin-based purified diets and Experiments 3 and 4
      with corn/soy-based practical diets. All experiments used day-old broiler
      cockerels and lasted 16 d. Silicon supplementation (250 mg/kg) significantly
      decreased growth rate and the incidence and severity of tibial dyschondroplasia
      in Experiment 1 and had no effect on either parameter in Experiments 2-4. Dietary
      silicon supplementation significantly reduced feed efficiency in Experiments 1
      and 3. Tibia bone ash was unaffected by dietary silicon supplementation in any of
      the experiments conducted. The results of the present studies indicate that
      dietary silicon supplementation has no effect on growth and skeletal development
      in broiler chickens.

PMID- 1995790
TI  - Copper uptake and transfer to the mouse fetus during pregnancy.
AB  - Accumulation of 64Cu in the 14-d mouse fetus was measured following intravenous
      injection of the dam with 64CuHis2. Concentration of 64Cu in the placenta
      increased rapidly over the first 4 h, thereafter remaining constant. Transfer to
      the fetus was linear over 48 h with little evidence of storage in the liver.
      Maternal serum levels decreased initially, concurrently with increased 64Cu
      levels in the maternal liver, but did not subsequently increase. Immediately
      following injection, as much as 40% of the radioactivity was in the nonalbumin
      fraction, and approximately 37% of that fraction (18% of total) was greater than
      30,000 molecular weight. After 24 h, up to 60% of the 64Cu was still found in the
      albumin peak. The data suggest that the fetus can obtain its Cu from maternal
      ceruloplasmin but does not exclude the possibility that transfer occurs from the
      exchangeable (albumin/amino acid) Cu pool of the maternal plasma. In a second
      experiment, mice at different stages of gestation were injected with 64Cu and
      killed 4 h later. Total Cu levels and 64Cu uptake into the maternal tissues or
      into the placenta did not change with increasing gestation. Both total Cu and
      64Cu uptake in the fetus and fetal liver increased to a maximum on d 16. Levels
      in the liver decreased thereafter to term, whereas levels in the rest of the
      fetus remained approximately constant. The pattern was similar whether the
      results were expressed per organ or per gram of fresh weight.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1995791
TI  - Interaction of somatotropin and genotype on the requirement for energy in two
      lines of finishing pigs.
AB  - Eighty barrows were used in a 2 x 2 x 4 factorial experiment to examine the
      effects of genetic line (Hampshire x Yorkshire, H x Y, and Yorkshire x Landrace,
      Y x L), somatotropin (dose, 0 and 5 mg/d) and energy intake (ad libitum, 93%, 86%
      and 80%) on growth performance and energy requirements for lean gain over the
      finishing phase of growth. Four diets were formulated to maintain equal intakes
      of protein, vitamins and minerals at different energy intakes. Somatotropin
      increased growth rate 30 to 35% across diets despite an 8 to 12% reduction in ad
      libitum feed intake. Lean growth rate (kg/d) was increased preferentially by ST
      in the faster-growing H x Y barrows, which showed a 2.8-fold greater maximum rate
      increase than the slower-growing Y x L barrows. In control barrows, 10%
      reductions in energy intake had no effect on lean gain and improved feed/lean
      gain about 10%. In somatotropin-treated barrows, lean gain was reduced with each
      energy restriction in H x Y; energy intake had no effect on lean gain in Y x L
      barrows. Feed/lean gain was improved 22% in Y x L barrows at the lowest energy
      intake. Data indicate that somatotropin accentuates breed differences in lean
      gain and energy requirements. Pigs with low lean-growth potential will benefit
      from restricted feeding, whereas strategies to increase energy intake in pigs
      with high lean-growth potential may be desirable.

PMID- 1995792
TI  - Principal gastrointestinal variables associated with metabolic heat production in
      pigs: statistical cluster analyses.
AB  - The purpose of this study was to classify organs/tissues into clusters according
      to their association with fasting heat production (FHP) by multivariate cluster
      analysis and to identify primary tissues. A data set consisting of 47 variables
      and 2256 data points was collected from 48 growing male pigs. Variance was
      perturbed by varying the daily feed allowance. Cluster analysis was conducted at
      each of six levels of body dissections, and a final analysis was conducted with
      all 47 variables. Small intestine, pancreas, liver, and kidneys were consistently
      assigned to the FHP-cluster; stomach, cecum, and colon to clusters correlated, r
      greater than 0.5, to the FHP-cluster; carcass, thoracic and offal variables to
      unrelated clusters. In the final analysis with all 47 variables represented, only
      variables from the small intestine and jejunum were assigned to the FHP-cluster.
      It is concluded that the small intestine, which accounts for only 2% of the body
      weight, is a primal organ system in swine and that pancreas, liver, and kidneys
      are of similar importance.

PMID- 1995793
TI  - Endotoxin and lipid peroxidation in vivo in selenium- and vitamin E-deficient and
      -adequate rats.
AB  - The effect of Salmonella typhimurium endotoxin injected intraperitoneally (0.5
      mg/kg body weight) on lipid peroxidation in vivo was assessed. Peroxidation was
      monitored by measuring ethane production, an autoxidation product of (n-3)
      unsaturated fatty acids. Weanling rats were fed a selenium- and vitamin E
      deficient basal diet or one supplemented with 0.2 mg Se/kg and/or 200 mg vitamin
      E/kg. After 11 to 13 wk of feeding, ethane production was tripled in LPS-treated
      Se- and vitamin E-deficient rats compared to saline-treated deficient rats. In
      both doubly deficient and adequate rats, LPS increased ethane production, but it
      did so to a greater extent in Se- and vitamin E-deficient rats. Dietary Se or
      vitamin E supplementation alone significantly reduced ethane production from LPS
      treated rats. Vitamin E was more protective than Se against LPS-induced lipid
      peroxidation. Escherichia coli and Salmonella minnesota LPS also increased ethane
      production in Se- and vitamin E-deficient rats. These results show that low doses
      of LPS stimulate lipid peroxidation in vivo in Se- and vitamin E-deficient rats.

PMID- 1995794
TI  - Endotoxin and lipid peroxidation in vitro in selenium- and vitamin E-deficient
      and -adequate rat tissues.
AB  - The effect of Salmonella typhimurium endotoxin injected intraperitoneally into
      rats (0.5 mg/kg of body weight) on subsequent lipid peroxidation in vitro was
      assessed. Peroxidation was monitored by measuring ethane production from tissue
      slices, as well as thiobarbituric acid-reactive substances and conjugated dienes
      in tissue homogenates. Weanling rats were fed a selenium- and vitamin E-deficient
      basal diet or one supplemented with 0.2 mg of Se/kg of diet and 200 mg of vitamin
      E/kg. After 9 to 16 wk, ethane production and thiobarbituric acid-reactive
      substances in liver and lung generally were increased by LPS treatment of Se- and
      vitamin E-deficient rats. Conjugated dienes were increased by LPS treatment in
      liver of Se- and vitamin E-deficient rats, but paradoxically, were higher in Se-
      and vitamin E-adequate liver tissue. Daily injections of 1 g of hydroxyurea/kg of
      body weight, a cell proliferation inhibitor, for 2 d prior to LPS injection
      significantly decreased the LPS-induced ethane production in Se- and vitamin E
      deficient rat liver and lung. These results show that low doses of LPS injected
      into rats stimulated lipid peroxidation in vitro in Se- and vitamin E-deficient
      rat liver tissue. Hydroxyurea decreased LPS-induced lipid peroxidation in vitro;
      this suggests that neutrophils or macrophages are involved in LPS-induced lipid
      peroxidation.

PMID- 1995796
TI  - Neurobehavioral effects of the on-call experience in housestaff physicians.
AB  - Sixty-tree medical residents were tested on a battery of computer-based, self
      administered neurobehavioral tests before and after a 36-hour in-hospital call
      plus postcall day to assess the central nervous system effects of the call
      experience and its accompanying sleep deprivation. Statistically significant
      decreases in performance were found postcall on tests of sustained visual
      attention (P less than 0.0001), speed and coding ability (P less than 0.0001) and
      short-term recall (P less than 0.0001). Hand-eye coordination improved (P less
      than 0.02).

PMID- 1995795
TI  - Nutrient intake variability in a pediatric population: implications for study
      design.
AB  - Estimates of an individual's intake of specific nutrients is important in
      epidemiologic investigations of disease-diet relationships. The object of the
      present investigation was to determine the minimum number of daily food records
      required to estimate intake of specific nutrients in children. Both members of 70
      pairs of twins (n = 140 children) completed a minimum of 3 and a maximum of 23
      food records throughout a 2-y period. All subjects were white and range in age
      from 5 to 14 y. Assuming an attenuation of the correlation coefficient of 80%,
      the minimum number of daily food records required to estimate energy intake was
      seven for boys and eight for girls. As a group, the vitamin intakes were the most
      variable for both boys and girls, often requiring more than 20 records for either
      sex. Requirements for other nutrients generally fell between these two extremes.
      The results of the present investigation are particularly relevant to the
      interpretation and design of studies of associations with nutrient intake.

PMID- 1995797
TI  - Screening for occupational asthma: a word of caution.
AB  - The diagnosis of occupational asthma may be difficult due to the complex
      mechanisms inducing the disorder. Identification of the offending agent after
      historical documentation may be difficult without bronchial challenge. The
      hallmark of asthma is bronchial hyperreactivity as detected by methacholine
      challenge, and this test could be considered as a screening test for asthma in
      the workplace. Four cases are presented that document changes in methacholine
      airway reactivity dependent on temporal association with exposure to the
      workplace or the specific offending agent. This indicates a need for a careful
      evaluation of symptoms relative to exposure in patients suspected for workplace
      asthma as well as serial determinations of methacholine response to detect
      potential variability in the airway reactivity.

PMID- 1995798
TI  - Blood cell proliferation response to beryllium: analysis by receiver-operating
      characteristics.
AB  - As testing for beryllium-induced proliferation of bronchoalveolar lavage cells is
      not suitable for screening, we evaluated the proliferative response of blood
      cells to beryllium. Twenty-seven patients with chronic beryllium disease,
      documented by histology and a positive lung proliferative response to beryllium,
      were compared to 30 controls. A significant difference (p less than .05) was
      observed between beryllium disease patients and controls with 100 or 10 microM
      beryllium salts. To evaluate the optimum test parameters and stimulation index
      cutoff, receiver operating characteristic curves (true positive v false positive)
      were generated. Maximum predictive value positive (26%) was observed at a
      stimulation index cutoff of 2.5 which corresponds to a 38% sensitivity and 97%
      specificity. This suggests that the blood cell proliferation response to
      beryllium has a limited role in screening for chronic beryllium disease.

PMID- 1995799
TI  - Use of population-based data to assess risk factor profiles of blue and white
      collar workers.
AB  - In light of increasing interest in the workplace as a site for primary prevention
      of chronic disease, more information concerning the current health status of
      workers is needed. This report compares "blue collar" (n = 2118) and "white
      collar" (n = 1900) respondents from a population-based random sample survey
      conducted in two southeastern New England communities. The specific responses
      were to a household interview and physiological measures emphasizing the risk
      factors for cardiovascular disease. These risk factors were elevated blood
      cholesterol, elevated blood pressure, smoking, being overweight and physical
      inactivity. Designation as blue or white collar was based upon the Standard
      Occupational Classification Manual. Gender specific comparisons of physiological
      status and self-reported knowledge attitudes and behaviors related to
      cardiovascular disease revealed that blue collar workers are at higher risk only
      for certain controllable risk factors, namely smoking and body mass index (women
      only). Contrary to other reports in the literature we have not found any
      significant difference in blood pressure or total cholesterol between the two
      groups. Even when people in high risk categories (systolic blood pressure greater
      than or equal to 140 mm/Hg, diastolic blood pressure greater than or equal to 90
      mm/Hg cholesterol greater than or equal to 240 mg/dL) were studied the
      distributions were equally similar in both blue and white collar workers among
      each gender group. These findings indicate that educational interventions should
      target all segments of the population regardless of the nature of their
      occupation. More emphasis should be placed on offering programs to increase
      knowledge and improve health-related attitudes of blue collar workers.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1995800
TI  - Respirator physiology research: answers in search of the question.
AB  - Adverse effects of respirators have been the focus of considerable research over
      the past decade. Individual research projects have generally focused on one
      specific category of effects: ventilatory, respiratory control, work limitation,
      subjective discomfort, psychologic effects, thermal loading, and cardiovascular
      changes. Most were studied in experimental laboratory situations rather than in
      actual worksites. Very little attention has been given to compliance with use and
      actual effectiveness in preserving health. Inasmuch as many types of effects have
      been demonstrated, there is a need to carefully define which type(s) of effects
      is/are most important for respirator design selection and worker medical
      certification in particular situations. In general, respirators should be
      assessed for their effect on all relevant variables.

PMID- 1995801
TI  - An update of mortality due to brain neoplasms and other causes among employees of
      a petrochemical facility.
AB  - In an update of an earlier investigation of brain tumors, mortality patterns were
      examined for 7849 male employees who worked at a petrochemical plant from 1941
      through 1983. The update added 6 years of observation (1978 to 1983). During this
      period, the brain tumor (BT) mortality risk declined relative to the US
      population, but continued to be higher than expected in hourly workers (5
      observed/3.4 expected). Similar to the earlier studies, BT occurrence was not
      explained by patterns of production work assignments. Mortality rates for hourly
      and salaried workers from all causes combined, total cancer and respiratory
      cancer were lower than US population rates. Lower rates for these causes were
      also seen for white and nonwhite production and maintenance workers. Liver cancer
      rates were greater than expected in white production workers (3 observed/1.6
      expected) and included two men assigned more than 40 years ago to vinyl chloride
      related departments. Mortality rates due to malignant melanoma were elevated in
      white maintenance workers (5 observed/2.0 expected) and may be explained by heavy
      sun exposure in outdoor work.

PMID- 1995802
TI  - Injuries among medical laboratory housekeeping staff: incidence and worker
      perceptions.
AB  - Housekeepers' injury experiences in medical laboratories have not been reported
      previously. Review of injury incident reports for housekeepers assigned to
      medical research laboratories in a major university revealed an incidence rate of
      46 injuries per 100 housekeepers per year from 1985 to 1988. Thirty-seven percent
      of the injuries were cuts and punctures, with 70% of these attributable to glass,
      needles, or cutting instruments. In a survey, 65% of housekeepers indicated that
      they do not always report their injuries, but the injury pattern they described
      paralleled those recorded in incident reports. Housekeepers identified behavioral
      and environmental factors that can contribute to laboratory injuries, including:
      lack of knowledge; failure to use protective equipment; carelessness; and,
      "sharps" (ie, sharp needles or glass) in the trash.

PMID- 1995803
TI  - Fatal occupational electrical injuries in Virginia.
AB  - Work-related electrical injuries and fatalities in Virginia were reviewed for the
      period 1977 to 1985. Of 196 workers electrocuted (0.9/100,000/year), 65% (127)
      died between May and September. Death rates were highest for male workers in
      utility companies (10.0/100,000), mining (5.9/100,000), and construction
      industries (3.9/100,000), but these high risk groups accounted for only 50% of
      the deaths. Most accidental electrocutions resulted from power line contact (53%)
      and machine or tool usage or repair (22%). Only 1.5% (2/101) of the workers who
      died within 6 hours of injury and had blood alcohol concentration tested were
      legally intoxicated. All workers need safety education on active measures to
      prevent hazardous electrical exposures, not just those at high risk for
      electrical injury. Every work-related electrical injury represents a sentinel
      health event--an opportunity for preventive intervention in the workplace.

PMID- 1995804
TI  - Fumigant intoxication during transport of grain by railroad.

PMID- 1995805
TI  - Health promotion in small business: what works and what doesn't work.
AB  - Wellness programs were tested in three sites, representing three different types
      of small businesses. The sites ranged in size from 296 to 5 employees. The
      program at each site included: 1) wellness screening, 2) referral to community
      physicians for high blood pressure or cholesterol, 3) on-site wellness programs,
      and 4) long-term follow-up counseling. At sites 2 and 3, the respective company
      paid the full cost of these services; at site 1, the company's financial support
      was limited to 50% of the cost of screening. Results showed that participation in
      screening was severely reduced in the third company, and participation in follow
      up and wellness programs dropped to zero. In contrast, there was full
      participation in all facets of the program at the two sites that paid all costs.
      Twelve-month follow-up data showed improvements in blood pressure, cholesterol,
      cigarette smoking, weight control, and oxygen uptake.

PMID- 1995806
TI  - Attitudes and behaviors of medical technologists as a result of AIDS.
AB  - To determine the influence of AIDS on the attitudes and behaviors of medical
      technologists, a survey was taken which shows that one quarter are considering
      leaving the field. Individuals who plan to stay in the profession are less
      fearful of AIDS, more satisfied with the policies their organizations have
      established regarding AIDS, and less willing to associate a declining employment
      situation to AIDS. Improvement in safe laboratory practices is present in both
      groups, but the individuals considering a move out of the field exhibit the
      largest change. A surprising result in that fear of AIDS is not related to or
      only weakly associated with traditional demographic and occupational variables,
      suggesting that other more complex factors are influencing the views and work
      habits of medical technologists as a result of AIDS.

PMID- 1995807
TI  - Ethical conflict in the private practice of occupational medicine.

PMID- 1995808
TI  - Morphologic study of the bone marrow of neutropenic patients exposed to benzene
      of the metallurgical industry of Cubatao, Sao Paulo, Brazil.

PMID- 1995809
TI  - Reproductive risks.

PMID- 1995810
TI  - Mandibular anatomy as it relates to rigid fixation of the sagittal ramus split
      osteotomy.
AB  - Rigid fixation of osteotomy segments is frequently used to reduce relapse and
      allow for early mobilization of the mandible following the sagittal ramus split
      osteotomy. This study evaluated cortical bone thickness in the retromolar area of
      49 human mandibles to determine if there is an advantage (in terms of cortical
      thickness) to placement of screws for rigid fixation at the external oblique
      ridge versus placement at the inferior border. The mandibles were sectioned
      vertically at three sites in the retromolar area, corresponding to the bone
      available for rigid fixation of the sagittal osteotomy. Cortical bone thickness
      was measured at the external oblique ridge and 5 mm above the inferior border.
      The buccal and lingual cortices were found to be significantly (P less than .001)
      thicker at the external oblique ridge than at the inferior border. This suggests
      that there may be an advantage in terms of stability to placement of internal
      fixation screws at the superior border.

PMID- 1995811
TI  - Reconstruction of the severely atrophic edentulous mandible by means of
      autogenous bone grafts and simultaneous placement of osseointegrated implants.
AB  - A method of reconstructing the severely atrophic mandible that simultaneously
      provides additional strength and the ability to house osseointegrated implants is
      presented. The performance of the procedure from an external approach minimizes
      the possibility of oral contamination and, therefore, infection. The procedure
      has been performed on 10 patients, with a longest follow-up of 3 years. A 93%
      success rate has been achieved, and bone resorption at the implant sites has thus
      far been negligible. Prosthetic rehabilitation has been done in 9 of the 10
      cases; 3 have been tissue-supported prostheses, and 6 have been completely
      implant-supported prostheses.

PMID- 1995812
TI  - Lag screw fixation of mandibular angle fractures.
AB  - This article presents a technique of applying lag screws for treating fractures
      of the mandibular angle. A review of 30 patients who had lag screws placed to
      treat such fractures showed that it is an extremely useful, but technique
      sensitive, method of providing rigid internal fixation. The advantages and
      complications of this technique over bone-plate fixation are discussed.

PMID- 1995813
TI  - The vascularized fibula graft in mandibular reconstruction.
AB  - The use of a vascularized graft from the fibula for mandibular reconstruction is
      presented. The great strength, pliability, and long vascular pedicle that
      characterize such grafts make them particularly suitable for this type of repair.
      The results in six cases were highly satisfactory. Masticatory function was well
      restored, without alteration of the facial contour, and with minimal sequelae at
      the donor site.

PMID- 1995814
TI  - Bone resorption, stability, and soft-tissue changes following large chin
      advancements.
AB  - Large advancement genioplasties were performed in 10 patients (mean advancement,
      11.7 mm) by horizontal osteotomy of the inferior border of the mandible, with
      preservation of a musculoperiosteal pedicle to the advanced genial segment.
      Preoperative, immediate postoperative, and long-term follow-up lateral
      cephalometric radiographs were retrospectively analyzed to evaluate the osseous
      and soft-tissue changes of the chin. After a mean follow-up period of 15 months,
      76% of the initial advancement was preserved, representing 24% osseous
      resorption. The enveloping soft tissues of the chin followed the bony movement in
      a ratio of 1:0.88. Horizontal osteotomy of the inferior border of the mandible
      was a relatively stable procedure when used for large chin advancements. The
      broadcast possible musculoperiosteal pedicle should remain attached to the
      advanced genial segment to minimize osseous resorption and to achieve more
      predictable soft-tissue changes.

PMID- 1995815
TI  - Fine-needle aspiration biopsy of head and neck lesions.
AB  - The case records of 213 fine-needle aspiration biopsies (FNAB) of head and neck
      masses performed on 209 patients over a 3-year period were reviewed to assess the
      diagnostic accuracy and safety of this technique in comparison with surgical
      histologic examination. Cytologic diagnoses based on FNAB were compared with
      histologic diagnoses in 110 patients who underwent surgery. Based on cytology
      alone, 40.3% of the lesions were reported as malignant, 45.1% as benign, and
      14.6% as indeterminant. A specific cytologic diagnosis was made in 85.5% of the
      cases. Cytologic diagnoses concurred with surgical histologic diagnoses 90% of
      the time. Fine-needle aspiration biopsy was found to have a false-positive rate
      of 0.5% and a false-negative rate of 2.3%. The sensitivity and specificity of
      FNAB in determining a malignant diagnosis were 81.1% and 99%, respectively.
      Positive and negative predictive values were calculated at 98.9% and 82.8%,
      respectively. Diagnostic rate, sensitivity, and negative predictive value
      increased consistently throughout the study period, indicating that the
      diagnostic accuracy of FNAB improved with experience.

PMID- 1995816
TI  - Nasopalatine duct cyst: an analysis of 334 cases.
AB  - The nasopalatine duct cyst (NPDC) is the most common cyst of nonodontogenic
      origin in the maxilla. However, the information reported about this lesion
      consists primarily of small surveys and isolated case reports. The purpose of
      this retrospective investigation was to gather demographic, clinical, and
      histologic data on a large series of NPDCs, and to compare the findings with
      those of previous studies. In this study, the overall mean age at diagnosis was
      42.5 years, and there was a slight male predilection. The mean radiographic
      diameter was 17.1 mm, but 75% of the lesions were 20 mm or less in diameter.
      Symptoms were present in at least 70% of the cases. Only 28% of the specimens
      contained respiratory epithelium. There was no correlation between radiographic
      size, patient's age, presenting symptoms, or type of epithelium. Recurrence was
      noted in only 2% of the cases.

PMID- 1995817
TI  - Creutzfeldt-Jakob disease from allogeneic dura: a review of risks and safety.
AB  - Surgeons and the lay public have recently expressed concern over the safety of
      allogeneic dura as it relates to the transmission of Creutzfeldt-Jakob Disease.
      Indeed, two cases have resulted from use of tissue procured from a commercial
      agency that did not adhere to criteria accepted by the American Association of
      Tissue Banks or the Southeast Organ Procurement Foundation. This review discusses
      the risks and safety of allogeneic dura. The findings should reassure the surgeon
      of the safety of allogeneic dura when it is properly processed and catalogued by
      a bona fide, reputable tissue bank. To date, there have been no documented cases
      reported to the Center for Disease Control in which Creutzfeldt-Jakob Disease was
      transmitted from allogeneic dura obtained from a registered tissue bank.

PMID- 1995818
TI  - Medical and dental implications of cocaine abuse.
AB  - With the ever-increasing supply of cocaine and use of "crack," the potent and
      smokeable form of cocaine, the dangers of cocaine abuse, with its high morbidity
      and mortality, have become recognized. Oral and maxillofacial surgeons may
      frequently and unknowingly be treating patients who use cocaine, and, therefore,
      they must be educated about cocaine-related problems and be prepared to deal with
      the complications. This article discusses the nature of cocaine, its
      pharmacology, systemic affects, the oral manifestations of cocaine abuse, and
      recommended clinical management of the patient.

PMID- 1995819
TI  - Wegener's granulomatosis: report of three cases with oral lesions.

PMID- 1995820
TI  - Liposarcoma arising in the cheek: report of a case and review of the literature.
AB  - The following points can be made about liposarcoma of the oral cavity: 1) it is
      rare and slow growing; 2) it is often mistaken for a benign lesion; 3) there is a
      direct correlation of microscopic appearance with biological behavior and
      prognosis; 4) treatment is primarily surgical, with radiation used for selected
      cases; and 5) the better-differentiated tumors seem to respond more favorably to
      radiation.

PMID- 1995821
TI  - Digital injury from a pulse oximeter probe.

PMID- 1995822
TI  - Posttraumatic septic superior sagittal sinus thrombosis: report of a case.

PMID- 1995823
TI  - Bilateral synovial cysts of the temporomandibular joint.

PMID- 1995824
TI  - Reconstructive rhinoplasty for rhinophyma: report of case.

PMID- 1995825
TI  - Oral manifestations of disseminated histoplasmosis in acquired immunodeficiency
      syndrome: report of two cases and review of the literature.

PMID- 1995826
TI  - Modified incisions to drain endodontically related abscesses.

PMID- 1995827
TI  - Tracheostomy scar revision using allogeneic dura.

PMID- 1995828
TI  - Mandibular discontinuity reconstruction.

PMID- 1995829
TI  - Hypoxemia in the postanesthetic recovery room.

PMID- 1995830
TI  - Equal opportunities for all.

PMID- 1995831
TI  - Information about litigation?

PMID- 1995832
TI  - A broader conception of mood experience.
AB  - The experience of a mood consists of more than emotional states such as
      happiness, anger, sadness, or fear. It also includes mood management processes
      that can facilitate or inhibit the experience of the mood reaction. A multidomain
      framework is described for organizing such experience, and 2 studies are reported
      that analyzed separately emotion-related and emotion-management-related mood
      experiences. In both studies, emotion-related experience, including physical,
      emotional, and cognitive subdomains, could be characterized by Pleasant
      Unpleasant and Arousal-Calm dimensions. Also, both studies yielded evidence for
      the emotion-management dimensions of Plans of Action, Suppression, and Denial.
      These broader dimensions of mood experience predicted criterion variables such as
      empathy better than Pleasant-Unpleasant and Arousal-Calm dimensions alone.

PMID- 1995833
TI  - Effects of physical threat and ego threat on eating behavior.
AB  - Restrained and unrestrained subjects were subjected to one of three distress
      manipulations prior to an ad lib taste task. The physical fear threat
      (anticipated electric shock) significantly decreased unrestrained subjects'
      eating and slightly increased restrained subjects' eating. Both ego threats
      (failure at an easy task or anticipating having to give a speech in front of an
      evaluative audience) significantly increased restrained subjects' eating but did
      not significantly suppress unrestrained subjects' eating. This pattern supports
      the proposition that physical fear differs from more general dysphoria in its
      effects on eating, perhaps because of the divergent effects of these two types of
      distress on eating control mechanisms, which in turn differ in restrained and
      unrestrained eaters.

PMID- 1995834
TI  - Absorption and hypnotizability: context effects reexamined.
AB  - Two independent studies failed to find evidence consistent with Council, Kirsch,
      and Hafner (1986), who argued that the repeatedly observed correlations between
      Tellegen's (1981) Absorption Scale (TAS) and hypnosis measures were artifacts of
      testing context, and de Groot, Gwynn, and Spanos (1988), who claimed evidence for
      a Gender x Context moderator effect. In the present studies, Ss completed the TAS
      and other personality questionnaires on 2 occasions: during an independent survey
      and later immediately prior to an assessment of hypnotizability. In Experiment 1
      (N = 475), the effect of context on the relation between questionnaire scores and
      hypnotizability was weak and variable; in Experiment 2 (N = 434), these weak
      effects were reversed. The results reaffirm the construct validity of absorption
      as both a major dimension of personality and as a predictor of hypnotic
      responsiveness.

PMID- 1995835
TI  - Preferences for separating or combining events.
AB  - This research investigates people's preferences for temporally separating or
      combining emotionally impactful events. For instance, do people prefer to
      experience 2 negative events (e.g., manuscript rejections) on the same day or on
      different days? Do people prefer to experience 2 positive events (e.g.,
      manuscript acceptances) on the same or different days? This article proposes a
      renewable resources model that combines elements of decision-making models
      (prospect theory) with the notion that people possess limited but renewable
      physiological, cognitive, and social resources for dealing with emotionally
      impactful events. As predicted, Ss preferred to separate 2 positive events (the
      gain-savoring hypothesis), to separate 2 negative events (the multiple-loss
      avoidance hypothesis), and to combine a positive and a negative event (the loss
      buffering hypothesis). Ss displayed identical preferences for events from the
      academic, financial, and social domains.

PMID- 1995836
TI  - Hardiness and stress moderation: a test of proposed mechanisms.
AB  - High and low hardy male and female undergraduates completed an evaluative threat
      task that was manipulated to influence appraisals of the task in a manner
      consistent with hardiness theory. High hardy subjects displayed higher
      frustration tolerance, appraised the task as less threatening, and responded to
      the task with more positive and less negative affect than did low hardy subjects.
      Although all subjects displayed increased heart rate (HR) in response to the
      experimental task, high hardy men displayed lower HR elevations during the task
      than did low hardy men. Hardiness did not influence HR responses among women.
      Manipulations of task appraisal revealed a similar pattern where men in the high
      hardiness appraisal conditions displayed lower levels of physiological arousal
      during the task than did men in the low hardiness appraisal conditions. Appraisal
      manipulations had either no effect or the opposite effect among women.

PMID- 1995837
TI  - Why rational people do irrational things. The theory of psychological reversals.
AB  - 1. The theory of psychological reversals holds that individuals are inherently
      inconsistent and that they reverse between metamotivational states. Four pair
      states have been identified: telic/paratelic; negativistic/conformist;
      mastery/sympathy; autocentric/allocentric. 2. Individuals interpret motivational
      variables in different ways depending on the metamotivational states in effect at
      the time. 3. Health-care providers should recognize that reversals between states
      are necessary for mental health and they should make allowances for such
      reversals in their health-care recommendations.

PMID- 1995838
TI  - Services for the underserved. A nurse-managed center for the chronically mentally
      ill.
AB  - 1. A university-based, nurse-managed center for the chronically mentally ill
      enhanced the experiences of baccalaureate nursing students with this underserved
      population. 2. The course objectives included psychosocial rehabilitation for
      chronic illness and provided a good fit between client's needs, course
      objectives, and the behavioral-ecological model. 3. The project positively
      changed the attitudes of nursing students. Changing attitudes of professionals
      and motivating student interest toward the chronically mentally ill is an
      imperative for meeting their needs.

PMID- 1995839
TI  - Promoting object constancy. Writing as a nursing intervention.
AB  - 1. Object constancy is an important developmental milestone that many psychiatric
      patients have not achieved. 2. Asking patients to write down thoughts and
      feelings will assist the nurse in reinforcing a continuous experience of self as
      a necessary antecedent to self and object constancy. 3. Object constancy allows
      the patient to be more autonomous in relationships. Writing will help the patient
      become more independent in managing thoughts and feelings. 4. Using an object
      relations framework for this commonly prescribed nursing intervention will assist
      nurses in providing a focus and goal for the use of writing.

PMID- 1995840
TI  - Dark nights and bright mornings: caring for a person with AIDS.

PMID- 1995841
TI  - Tourette's syndrome.
AB  - 1. Tourette's syndrome is a disorder with a multitude of complex behavioral
      problems with major implications for social impairment and emotional pain. 2. The
      generic care plan anticipates the predictable management problems in adolescent
      patients. It offers nursing interventions, particularly structure, which is
      important in managing symptoms. 3. The treatment process is slow. The successful
      implementation requires consistent efforts from the nursing staff, treatment
      team, and family.

PMID- 1995842
TI  - Improved development of rabbit one-cell embryos to the hatching blastocyst stage
      by culture in a defined, protein-free culture medium.
AB  - In Exp. 1, Medium 199 and Medium RD (RPMI-1640 and Dulbecco's MEM, 1:1 v/v) were
      compared in a 2 x 2 factorial design by supplementing each with 15 mg bovine
      serum albumin (BSA)/ml of 1 mg polyvinyl alcohol (PVA)/ml. All media contained 5
      micrograms insulin/ml, 5 micrograms transferrin/ml, 5 ng selenium/ml (ITS), and
      10 ng epidermal growth factor (EGF)/ml. One-cell embryos were cultured at 39
      degrees C with 5% CO2 in air for 65 h and then stained with Hoechst 33342 to
      determine blastomere number. Embryos in Medium 199 developed poorly (P less than
      0.001) when PVA was used instead of BSA (30 vs 76 cells/embryo), but developed
      rapidly in Medium RD with PVA or BSA (118 and 121 cells). Similar results were
      obtained in Exp. 2 in BSA- and PVA-free medium. In Exp. 3, the development of 1
      cell embryos after 65 h in unsupplemented (protein-free) Medium RD (68%
      blastocysts, 117 cells) did not differ (P greater than 0.37) from that obtained
      using Medium RD with insulin, ITS or EGF alone. Culture in protein-free Medium RD
      for 96 h resulted in 82% of the 1-cell embryos forming blastocysts and 40%
      hatching through the zona pellucida. In a preliminary test of viability, 1-cell
      embryos cultured in this medium for 48 or 65 h and transferred to synchronous
      recipients resulted in 5/18 (28%) and 3/24 (12%) Day-15 viable fetuses. Cell
      counts of approximately 120 per blastocyst after culturing 1-cell embryos for 65
      h in Medium RD indicated that cell division was more rapid than that obtained
      with all other media tested previously in this laboratory. This is the first
      report of rabbit embryo development from the 1-cell to the hatching blastocyst
      stage in a defined protein-free culture medium.

PMID- 1995843
TI  - Comparative metabolism of spermatozoa from subfertile Delaware and Wyandotte
      roosters.
AB  - Sperm metabolism was determined via reduction of 2-(p-iodophenyl)-3-(p
      nitrophenyl)-5-phenyl tetrazolium chloride (INT) to formazan. When the reaction
      mixture contained cyanide, which blocks cytochrome oxidase and thus maximizes
      intermediate electron transfer to INT, and calcium which stimulates fowl sperm
      motility, the metabolic capacity of spermatozoa from subfertile Delaware and
      Wyandotte roosters was 90 and 63% of that of spermatozoa from fertile Leghorn
      roosters. When the assay was performed at 40 degrees C without calcium or
      cyanide, no difference in metabolism was observed between Delaware and Leghorn
      spermatozoa (P greater than 0.05). However, the metabolism of Wyandotte
      spermatozoa was 66% of that observed with Delaware or Leghorn spermatozoa. These
      results provide further evidence that heritable subfertility in Delaware and
      Wyandotte roosters is attributable to distinct sperm defects.

PMID- 1995844
TI  - LH secretion and response to GnRH during seasonal anoestrus of the Pere David's
      deer hind (Elaphurus davidianus).
AB  - The pattern of LH secretion and response to exogenous GnRH was determined on 5
      occasions during seasonal anoestrus of the Pere David's deer hind. LH pulse
      frequency was low (3.3 +/- 0.6 pulses/18 h) in early anoestrus (February),
      increased significantly in mid-anoestrus (April; 8.4 +/- 1.4 pulses/18 h) and
      thereafter declined slightly in late anoestrus (June; 6.3 +/- 0.25 pulses/18 h).
      Mean LH concentrations also showed significant changes during anoestrus with
      higher levels in mid-anoestrus (April; 0.85 +/- 0.12 ng/ml) when compared with
      other times (0.53 +/- 0.05, 0.60 +/- 0.10, 0.68 +/- 0.06 and 0.71 +/- 0.05 ng/ml
      for February, March, May and June, respectively). LH pulse amplitude showed no
      significant changes during the study. The LH response to intravenous injections
      of 2 micrograms GnRH was lowest in early anoestrus (February), increased
      significantly in mid-anoestrus (April) and remained high through late anoestrus.
      The response during the luteal phase was similar to that seen during late
      anoestrus. These results indicate that seasonal anoestrus in the Pere David's
      deer hind is not a uniform state but is characterized by an early period of
      'deep' anoestrus.

PMID- 1995845
TI  - Altered androstenedione to testosterone ratios and LH concentrations during musth
      in the captive male Asian elephant (Elephas maximus).
AB  - Greater concentrations of androstenedione than testosterone were usually present
      during periods of non-musth in plasma collected weekly for various periods up to
      2 years in 8 male Asian elephants (4-35 years of age). For the 6 males that
      exhibited musth the androstenedione/testosterone ratio shifted greatly in favour
      of testosterone. The severity of musth was assessed weekly using a scale of 1 to
      5 for each of 8 behavioural traits including urine dribbling, temporal gland
      secretion and aggression. A significant correlation (P less than 0.05) was noted
      between plasma testosterone concentrations and the musth score value in 5 of 6
      musth episodes. Brief shifts in the ratio of two androgens when testosterone
      predominated (n = 106) were seen during the non-musth period in 3 of the males
      studied continuously for 2 years. In 82% of these instances, stimuli of a sexual
      or aggressive nature had occurred in the preceding 48 h (chi 2, P less than
      0.01). A heterologous bovine assay was used to measure LH values in plasma
      collected every 15 min for 12 h. Increases in testosterone concentrations
      followed pulsatile increases in plasma LH concentrations during 7 non-musth
      periods in 4 animals. Apart from pulse frequency, increases in the variables
      describing pulsatile LH secretion were seen in 2 strong musth and 2 mild musth
      episodes compared to non-musth values. A strong musth, however, was characterized
      by a much greater increase in pulsatile testosterone secretion than was a mild
      musth and which may be a function of the duration of musth.

PMID- 1995846
TI  - Characterization of intraepithelial lymphocytes in human endometrium.
AB  - Intraepithelial lymphocytes (IELs) were characterized and quantitated in normal
      non-pregnant endometrium and in early pregnancy decidua using H & E and phloxine
      tartrazine stains and a panel of monoclonal antibodies in an indirect
      immunoperoxidase technique. The relative numbers of granulated and non-granulated
      IELs varied according to menstrual cycle stage and in early pregnancy all IELs
      appeared to be granulated. There was a higher surface:gland ratio for IELs in
      proliferative endometrium compared with late secretory phase and early pregnancy
      endometrium. In proliferative endometrium most IELs were T cells, predominantly
      of the CD8 + subset. In first trimester decidua, higher numbers of CD56 + cells
      were observed, in keeping with the increased proportion of granulated IELs. IEL
      populations in human endometrium vary according to menstrual cycle stage and
      endometrial IELs appear to show phenotypic differences compared with IELs in the
      human gastrointestinal tract.

PMID- 1995847
TI  - Profiles of hypoxanthine guanine phosphoribosyl transferase and adenine
      phosphoribosyl transferase activities measured in single preimplantation human
      embryos by high-performance liquid chromatography.
AB  - The profiles of hypoxanthine guanine phosphoribosyl transferase (HGPRT) and
      adenine phosphoribosyl transferase (APRT) activities were examined in normally
      fertilized human embryos developing at the normal rate in vitro between the 2-4
      cell stage on Day 2 and the blastocyst stage on Day 6 after insemination. The
      activities of both enzymes were assayed simultaneously in extracts of single
      embryos by measuring the rate of production of the reaction products, inosine
      monophosphate (IMP) and adenine monophosphate (AMP), separated by high
      performance liquid chromatography (HPLC). The activity profiles of the two
      enzymes over this period showed marked differences. The activity of HGPRT, coded
      by the X chromosome, increased between Days 2 and 4 (P less than 0.01) but
      declined sharply by Day 6 (P less than 0.001), whereas autosome-coded APRT
      activity remained low between Days 2 and 5, but increased on Day 6 (P less than
      0.05). The profile of HGPRT activity may reflect a combination of decreasing
      levels of maternal enzyme inherited from the oocyte and the initiation of
      embryonic gene expression followed by X inactivation at the blastocyst stage on
      Day 6.

PMID- 1995848
TI  - Replication status of the fragile X chromosome and its implications for
      reproductive performance in the Indian mole rat (Nesokia indica).
AB  - In all fertile females the fragile X chromosome was almost always late
      replicating (inactive) in an average 82% of cells whereas in infertile females,
      it was early replicating (active) in about the same percentage of cells. These
      observations strongly suggest a correlation between the replication (activity)
      status of the fragile X chromosome and reproductive performance.

PMID- 1995849
TI  - Effect of inhibition of oxygen free radical on ovulation and progesterone
      production by the in-vitro perfused rabbit ovary.
AB  - The potential role of oxygen free radicals in hCG-induced ovulation was
      investigated using the free radical scavenging enzymes superoxide dismutase (SOD)
      and/or catalase with the in-vitro perfused rabbit ovary preparation. SOD (25
      micrograms/ml) and SOD + catalase (25 micrograms/ml) significantly reduced the %
      of large follicles that ovulated during perfusion (P less than 0.005). Neither
      maturity nor degeneration of ovulated ova and follicular oocytes was affected by
      SOD and/or catalase. Progesterone concentration in the perfusate was
      significantly increased in the SOD + catalase treatment group (P less than 0.01).
      These results indicate a significant role for oxygen free radicals in the process
      of ovulation.

PMID- 1995850
TI  - A timetable of embryonic development, and ovarian and uterine changes during
      pregnancy, in the stripe-faced dunnart, Sminthopsis macroura (Marsupialia:
      Dasyuridae).
AB  - Aged stages (63) were available for establishment of a timetable of embryonic
      development of the stripe-faced dunnart. On Day 0 oocytes reaching maturity were
      found in the ovary. Within +/- 24 h of time 0 (time of minimum morning weight)
      polymorphonuclear leucocytes appeared and spermatozoa were last detected in the
      urine of 70% of females. Embryos were collected at intervals during pregnancy by
      hemihysterectomy and the embryos in the contralateral uterus either were examined
      at a later stage of pregnancy or allowed to develop to term. Cleavage to the
      unilaminar blastocyst stage with around 32 cells took 3 days with a cleavage
      arrest of 24 h at the 4-cell stage. Expansion of the unilaminar blastocyst
      occurred over the next 3 days. Primitive endoderm cells appeared on Day 6, fully
      bilaminar blastocysts by the end of Day 7 and trilaminar blastocysts on Day 8.
      Shell loss and implantation of 13-15-somite stage embryos occurred on Day 8 and
      organogenesis over the next 2-3 days. The gestation period was 9.5-12.0 days with
      most births occurring between 10.5 and 11.0 days. Major steps in embryonic
      development were correlated with stages in the development of the corpora lutea,
      which were maximal in size, and possibly in secretory activity, when the embryos
      were at the bilaminar blastocyst stage. Regression commenced when the embryos
      were at the primitive streak stage. At the time the corpora lutea were maximal
      the uterine epithelium reached its greatest height and the endometrium was thick
      and folded. Later in pregnancy villous-like projections of the epithelium formed,
      and the luminal epithelial cells became rounded. Two cell populations, a tier of
      8 smaller cells above the yolk mass and a tier of 8 larger cells around the sides
      of the yolk mass appeared at the 16-cell stage. From the 16-cell stage to the
      blastocyst stage, with 150-200 cells, two cell populations distinguished by size,
      cell cycle time, cytoplasmic appearance and position relative to the yolk mass
      were present. The two populations were indistinguishable in blastocysts with
      greater than 200 and less than 2000 cells. They reappeared in blastocysts with
      greater than 2000 cells, as the darker cells of the embryoblast, and as the paler
      cells of the trophoblast. The darker cells lay in the yolky hemisphere and the
      paler cells in the non-yolky hemisphere.

PMID- 1995851
TI  - Efficacy of intermittent or continuous administration of GnRH in inducing
      ovulation in early and late seasonal anoestrus in the Pere David's deer hind
      (Elaphurus davidianus).
AB  - Pere David's deer hinds were treated with GnRH, administered as intermittent i.v.
      injections (2.0 micrograms/injection at 2-h intervals) for 4 days, or as a
      continuous s.c. infusion (1.0 micrograms/h) for 14 days. These treatments were
      given early (February-March) and late (May-June) in the period of seasonal
      anoestrus. The administration of repeated injections of GnRH increased mean LH
      concentrations from pretreatment values of 0.54 +/- 0.09 to 2.10 +/- 0.25 ng/ml
      over the first 8 h of treatment in early anoestrus, and from 0.62 +/- 0.11 to
      2.73 +/- 0.49 ng/ml in late anoestrus. The mean amplitude of GnRH-induced LH
      episodes was greater (P less than 0.01) in late (4.03 +/- 0.28 ng/ml) than in
      early (3.12 +/- 0.26 ng/ml) anoestrus, but within each replicate (early or late
      anoestrus), neither mean LH episode amplitude nor mean plasma LH concentrations
      differed significantly between the four periods of intensive blood sampling. On
      the basis of their progesterone profiles, 6/12 hinds had ovulated in response to
      treatment with injections of GnRH (1/6 in early anoestrus and 5/6 in late
      anoestrus), and oestrus and a preovulatory LH surge were recorded in all of these
      animals. Oestrus and a preovulatory LH surge were also recorded in one other
      animal treated in early anoestrus in which progesterone concentrations remained
      low. The mean times of onset of oestrus (91.0 +/- 1.00 and 62.4 +/- 0.98 h) and
      of the preovulatory LH surge (85.8 +/- 3.76 and 59.4 +/- 0.25 h) both occurred
      significantly earlier (P less than 0.001) in animals treated in late anoestrus.
      Continuous infusion of GnRH to seasonally anoestrous hinds resulted in an
      increase in mean plasma LH concentrations, but this response did not differ
      significantly between early (2.15 +/- 0.28 ng/ml) and late (2.48 +/- 0.26 ng/ml)
      anoestrus. Ovulation, based on progesterone profiles, occurred in 2/7 hinds in
      early anoestrus and in 4/6 hinds in late anoestrus. Oestrus was detected in all
      except one of these hinds. The mean time of onset of oestrus occurred earlier in
      animals treated in late anoestrus (66.2 +/- 0.32 h and 46.7 +/- 0.67 h, P less
      than 0.01). The administration of GnRH, given either intermittently or
      continuously, will induce ovulation in a proportion of seasonally anoestrous Pere
      David's deer. However, more animals ovulate in response to this treatment in late
      than in early anoestrus (75% compared with 23%).

PMID- 1995852
TI  - Identification of a putative inhibitor of early pregnancy factor in mice.
AB  - Previous studies have indicated that early pregnancy factor (EPF) produced in the
      pre- and peri-implantation stage of pregnancy appears to consist of inactive
      components which combine to produce the active species. This is in contrast with
      EPF produced later in gestation which appears to consist of a single active
      species. The original studies on ammonium sulphate fractionation of mouse serum
      and in-vitro culture of mouse ovaries and oviducts have been repeated but tested
      in the bioassay for EPF, the rosette inhibition test, over an extended range of
      dilutions. This revealed that the two components in early pregnancy can be
      understood as EPF and an inhibitor(s). Once this inhibitor is removed, the active
      fractions in both early and late pregnancy sera exhibit similar behaviour in the
      above assay. It was shown also that the ovary alone is the source of activity but
      that this is modulated by an inhibitory substance(s) from the oviduct. Reversed
      phase HPLC studies on purified 'early' EPF confirm that active and inhibitory
      components are present and demonstrate that the active component exhibits an
      identical elution pattern to 'late' EPF. Thus as pregnancy proceeds, it is not
      EPF that alters but rather the inhibitor(s), which disappears from the
      circulation soon after implantation. This substance(s) is under hormonal control,
      being present during oestrus as well as the early stages of pregnancy; it may be
      an important biological regulator of EPF. Its action in the rosette inhibition
      test has profound implications for further study using this bioassay.

PMID- 1995853
TI  - Prolactin enhances uteroglobin gene expression by uteri of immature rabbits.
AB  - The effect of prolactin on uteroglobin production by immature rabbits was studied
      with neonatal (1 day old) and juvenile (14 days old) does. The animals were
      divided into 11 treatment groups for each age category and exposed to a 9-day
      injection protocol. Each day the animals received a subcutaneous injection of
      oestradiol-17 beta and/or ovine prolactin and/or progesterone, or were sham
      injected. Juvenile animals, which received 100 micrograms oestradiol/kg 24 h-1,
      plus progesterone or plus prolactin and progesterone, produced detectable amounts
      of uteroglobin in the uterine secretions (0.034 +/- 0.010 mg uteroglobin/mg total
      protein and 0.098 +/- 0.03 l mg uteroglobin/mg total protein, respectively). None
      of the animals in the other juvenile treatment groups or any of the neonatal
      groups produced uteroglobin. From this survey it was apparent that uteroglobin
      secretion could be induced by exogenous oestradiol and progesterone in rabbits
      treated as early as 14 days of age, and that the added supplementation of
      prolactin enhanced the response to the ovarian steroids. As a result, additional
      juvenile animals were injected with 100 micrograms oestradiol +/- prolactin +
      progesterone and the effects of these two treatments were quantitated as follows:
      uteroglobin mRNA levels by slot-blot hybridization; endometrial surface area by
      computerized image analysis; and oestrogen, progesterone and prolactin receptors
      by immunocytochemistry. Prolactin modified the response of the juvenile rabbit
      uterus to oestradiol + progesterone for all parameters tested.

PMID- 1995854
TI  - Immunohistochemical localization of testicular sulphydryloxidase during sexual
      maturation of the Djungarian hamster (Phodopus sungorus).
AB  - Immunohistochemical localization of sulphydryloxidase was examined in the testis
      of the Djungarian hamster from Day 0 to Day 31 of post-natal development. The
      sulphydryloxidase antibody labelled prespermatogonia and the first population of
      spermatogonia type A within the seminiferous epithelium. Additionally, Sertoli
      cells exhibited immunoreactivity from Day 2 to Day 11 after birth. From Day 11
      onwards, sulphydryloxidase immunoreactivity was found in germ cells after the
      initiation spermatogenesis from pachytene primary spermatocytes, showing the
      highest intensity in mid-pachytene spermatocytes. The pattern of
      sulphydryloxidase expression during spermatogenesis was identical to that found
      in adult animals. It is concluded that sulphydryloxidase immunoreactivity not
      only serves as a marker for early stages of spermatogenesis, especially pachytene
      spermatocytes, confirming earlier reports, but also for spermatogonial
      precursors.

PMID- 1995855
TI  - Paracrine interactions between platelet-activating factor and prostaglandins in
      hormonally-treated human luteal phase endometrium in vitro.
AB  - Stromal cells and epithelial glands were separated after enzymic digestion of
      specimens obtained from 27 women at hysterectomy or endometrial biopsy during the
      luteal phase, and then cultured to confluence in vitro. PGE release into the
      culture medium (mean +/- s.e.m.: ng/mg protein/24 h) from gland cell cultures was
      not changed by oestradiol (17.6 +/- 1.3 for control and 25.5 +/- 2.8 for
      oestradiol, respectively). However, in the presence of oestradiol, PAF (5 ng/ml)
      significantly elevated PGE release to 44.2 +/- 5.8. No stimulation was observed
      in the presence of progesterone. Stromal cell medium had no effect on PGE release
      in gland cell cultures. PGE release was always much lower in stromal cell
      cultures than in glands (control: 4.7 +/- 0.6). PAF stimulated PGE release in the
      presence of oestradiol in these cells also; gland cell medium was without effect.
      In co-cultures of glandular and stromal cells, PGE release was more similar to
      that seen in gland cell cultures, with PAF being stimulatory under the influence
      of oestradiol. PGF release into the medium from the same gland cell cultures was
      significantly elevated by hormonal treatment, being greatest (62.0 +/- 11.3) with
      oestradiol alone, and was strongly inhibited in all wells by addition of PAF and
      stromal cell medium. In stromal cell cultures without hormonal addition, PGF
      levels (15.0 +/- 2.4) were similar to those seen in glands (18.1 +/- 3.1), and no
      stimulation was achieved by oestradiol (29.6 +/- 5.9). PAF was inhibitory on PGF
      release, while gland cell medium was without effect. Co-cultures gave PGF values
      generally similar to those of stromal cells; oestradiol was again stimulatory
      (55.0 +/- 9.3). PAF was significantly inhibitory in the presence of oestradiol.
      PAF (mean +/- s.e.m.: pmol/mg protein/24 h using a platelet serotonin release
      assay) in stromal cells was significantly increased from control [M199 alone]
      (0.31 +/- 0.12) by progesterone (1.00 +/- 0.17). Addition of PGE-2 (7.5 ng/ml) to
      progesterone-treated wells further increased PAF concentration (5.34 +/- 0.09),
      but was without effect in wells receiving oestradiol alone. Wells exposed to both
      hormones exhibited an intermediate response. Similar results were obtained with
      addition of gland cell culture medium, presumably due to its endogenous PGE
      content. In co-cultures, PAF concentrations were significantly elevated by
      progesterone alone (4.78 +/- 0.78) or when combined with oestradiol (2.38 +/-
      0.51), but not by oestradiol alone. Treatment with PGE-2 caused no additional
      stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1995856
TI  - Penetration in vitro of bovine oocytes during maturation by frozen-thawed
      spermatozoa.
AB  - Bovine immature oocytes cultured for various times in TC-199 medium were
      inseminated with frozen-thawed spermatozoa in Medium BO with caffeine (5 mM) and
      heparin (10 micrograms/ml). Very high penetration rates (95-100%) were obtained
      in all oocytes which had been cultured for 0-20 h. When oocytes cultured for 0
      and 4 h were inseminated, 100% of them were penetrated and had a decondensing
      sperm head and most of the oocytes remained at the stage of condensed germinal
      vesicle (GV) to telophase-I 20-22 h after insemination. The formation of male and
      female pronuclei was first observed in oocytes inseminated 8 h after culture. The
      proportions of polyspermy and average number of spermatozoa in penetrated oocytes
      gradually decreased as oocyte maturation proceeded. Penetration of at least one
      spermatozoon with a decondensing head into oocytes at the GV stage (without
      culture) was almost completed up to 8 h after insemination and at that time most
      of the penetrated oocytes were still at the stage of GV or condensed GV. These
      results indicate that maturation of bovine oocytes is not required for sperm
      penetration into the vitellus or for sperm nuclear decondensation under the in
      vitro conditions used.

PMID- 1995857
TI  - Pulsatile release of oxytocin into the circulation of the ewe during oestrus,
      mating and the early luteal phase.
AB  - Two experiments were designed to investigate release patterns of oxytocin into
      plasma during oestrus and the early luteal phase. In Exp. 1, blood samples were
      collected from 5 ewes every 30 min for 10 h during 6 days around oestrus and the
      early luteal phase. During oestrus concentrations of oxytocin were generally low
      (1.27 +/- 0.54 pg/ml; mean +/- s.d.) but with occasional pulses up to 6 pg/ml. By
      Day 5 mean basal concentrations had risen to 4.5 +/- 2.1 pg/ml with a fluctuating
      release pattern. In Exp. 2, a method was developed for continuous blood sampling
      from conscious, unrestrained ewes. On the predicted day of oestrus following an
      untreated oestrous cycle, 8-ml blood samples were collected every minute for two
      35-min periods (8 ewes: 16 sampling periods). For 6 ewes a ram was introduced to
      the pen for part of this time, and resulting behaviour was recorded. Additional
      blood samples were assayed for LH and progesterone to determine the stage of the
      cycle. Overall mean oxytocin concentrations ranged from 1.5 +/- 0.53 to 6.8 +/-
      5.25 pg/ml in different animals. Ewes which were both in oestrus and exposed to
      the ram showed a pulsatile oxytocin release pattern consisting of low baseline
      concentrations with short-duration pulses superimposed (duration 1-4 min;
      amplitude 2.5-31.7 pg/ml; frequency 3.18/h). Coitus was not temporally associated
      with pulsatile release. However, the importance of the presence of the ram was
      indicated by total separation of 2 oestrous ewes from the ram until after
      experimentation. In these animals only 1 pulse of oxytocin was detected in 2.7 h
      of sampling. It is concluded that, although mean oxytocin concentrations at
      oestrus were low, short duration pulses were released into the plasma at this
      time. This effect may be dependent on the presence of a ram.

PMID- 1995858
TI  - Effect of injected bovine interferon-alpha I1 on estrous cycle length and
      pregnancy success in sheep.
AB  - In Exp. 1 twice daily i.m. injections of 2 mg recombinant bovine IFN-alpha I1
      (rboIFN-alpha I1) (N = 24) or placebo (N = 25) were administered to ewes from Day
      12 to Day 16 during a normal oestrous cycle. Treatment did not increase (P
      greater than 0.10) oestrous cycle length (20.7 +/- 1.2 versus 18.5 +/- 1.4 days).
      In Exp. 2, ewes were injected twice daily with 2 mg IFN (N = 34) or placebo (N =
      36) from Days 11 to 18 after natural mating. The rboIFN-alpha I1 significantly (P
      = 0.05) improved pregnancy rate (79% versus 58%) as determined by a failure of
      ewes to return to oestrus within 50 days. The number of ewes that lambed was
      greatest in the rboIFN-alpha I1-treatment group (71% versus 50%; P = 0.07), and
      no teratogenic effects were observed in the young born to IFN-treated ewes. The
      study was repeated a second year with a more fecund group of ewes (Exp. 3). More
      (P = 0.08) ewes injected with rboIFN-alpha I1 (58/65) than placebo-treated ewes
      (48/61) were judged pregnant by ultrasound. Again more ewes lambed (55 versus 45)
      and more lambs were born (98 versus 80) from the rboIFN-alpha I1-treated group.
      Combining the data from both studies revealed a significant (P = 0.01) effect of
      treatment. The amount of antiviral activity in jugular vein blood of ewes
      injected with rboIFN-alpha I1 (2 mg) was determined over time in Exp. 4. Activity
      rose to a maximum (approximately 450 IRU/ml) within 1-2 h and declined by over
      75% in 24 h. Single injections of 1, 2 and 5 mg in buffer or 2 mg emulsified in
      sesame oil all gave similar profiles of antiviral activity in jugular blood over
      a 48-h period. In Exp. 5, antiviral activity was measured in uterine vein,
      ovarian artery and jugular vein serum of untreated pregnant (N = 7) and non
      pregnant (N = 11) ewes at Day 15 after mating. Activity was detected in the
      uterine vein (58 +/- 19 IRU/ml) of all pregnant ewes. The observations in Exps 1
      5 are consistent with a role for conceptus-derived IFN-alpha in maternal
      recognition of pregnancy and suggest that supplemental IFN-alpha might be useful
      in improving pregnancy success in sheep.

PMID- 1995859
TI  - Infiltration of neutrophil polymorphonuclear leucocytes into the endometrial
      stroma at the time of implantation of ova and the initiation of the oil decidual
      cell reaction in mice.
AB  - Polymorphonuclear leucocytes (polymorphs) were found in the endometrial stroma
      adjacent to implanting blastocysts approximately 100 h after mating. Areas of
      uterus not containing a blastocyst had very few polymorphs. Ovariectomized mice
      were treated with hormones to render them sensitive to a decidual stimulus, the
      intraluminal injection of arachis oil. Areas of uterus responding to the oil (as
      indicated by the Pontamine Sky Blue reaction) showed an influx of leucocytes into
      the endometrial stroma between 16 and 36 h after the application of the decidual
      stimulus. The polymorphs were largely neutrophils. The injection of oil into non
      sensitized uteri did not result in polymorph infiltration nor did the injection
      of physiological saline (which is not deciduogenic) into sensitized uteri. It is
      concluded that during the early stages of decidualization there is attraction of
      polymorphs from the blood into the stroma.

PMID- 1995860
TI  - A possible explanation for the refractoriness of uterine prostaglandin
      production.
AB  - Arachidonic acid increased the outputs of prostaglandin (PG) F-2 alpha, PGE-2 and
      6-keto-PGF-1 alpha from the Day-7 and Day-15 guinea-pig uterus superfused in
      vitro. Similar increases in PG output were observed when the arachidonic acid
      treatment was repeated after an interval of 1, 3 or 5 h. Phospholipase (PL) A-2
      increased the outputs of PGF-2 alpha, PGE-2 and 6-keto-PGF-1 alpha from the Day-7
      guinea-pig uterus, but repeating the PLA-2 treatment 1 h later failed to
      stimulate PG output. The increase in outputs of PGF-2 alpha and PGE-2 caused by
      PLA-2 were partly restored after 3 h and were fully restored after 5 h, whereas
      the increase in 6-keto-PGF-1 alpha output produced by PLA-2 was only partly
      restored after 3 and 5 h. PLA-2 had little or no effect on PGF-2 alpha and PGE-2
      outputs from the Day-15 guinea-pig uterus initially, and when repeated after 1, 3
      and 5 h. This was probably due to the output of these two PGs, particularly of
      PGF-2 alpha, being stimulated in vivo before removal of the uterus. PLA-2
      increased 6-keto-PGF-1 alpha output from the Day-15 uterus initially, but failed
      to cause a response when administered again 1 h later. After 3 and 5 h, the
      increase in 6-keto-PGF-1 alpha output from the Day-15 uterus caused by PLA-2 was
      partly restored. A23187 and PLC increased the outputs of PGF-2 alpha, PGE-2 and 6
      keto-PGF-1 alpha from the Day-7 and Day-15 guinea-pig uterus. These responses to
      A23187 and PLC were reduced (but not abolished) when the two compounds were
      administered again 1 h later. After 3 and 5 h, the increases in output of PGF-2
      alpha and PGE-2 produced by A23187 and PLC had returned to the initial values.
      The increases in output of 6-keto-PGF-1 alpha from the Day-7 and Day-15 guinea
      pig uterus produced by A23187 and PLC were partly restored after 3 and 5 h,
      except for the response to PLC on Day 7 which was fully restored after 5 h. The
      results show that there is no failure with time in the mechanism which converts
      arachidonic acid into PGF-2 alpha in the guinea-pig uterus.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 1995861
TI  - Effects of food restriction and social cues on sexual maturation and growth in
      male musk shrews (Suncus murinus).
AB  - In the first experiment, the effects of food availability on growth and
      reproduction were assessed by placing male musk shrews on 3 different feeding
      schedules, i.e. fed ad libitum, fed 50% of the amount eaten by the ad-libitum
      controls or fed 25% of the amount eaten by the ad-libitum controls. After 25
      days, growth and sexual maturation were significantly retarded in both of the
      food-restricted groups compared to the control group. In the second experiment,
      the combined effects of food availability and social cues were investigated in
      juvenile males that were either fed ad libitum (during the day) or placed on a
      restricted diet known to inhibit growth and reproduction. Half of these males
      were either housed alone or with an adult female (separated from female during
      the day by a wire barrier, but in full contact at night). The ad-libitum-fed
      males living with a female ate more food, gained more body weight and were more
      sexually mature than ad-libitum-fed animals living alone. Furthermore, males in
      the two food-restricted groups had lower body weights and were sexually immature
      compared with males in both of the ad-libitum-fed groups. Finally, there were
      little or no differences in growth and reproduction between animals in the two
      food-restricted groups. These results suggest that food availability is an
      important environmental regulator of the timing of sexual maturation, and that
      stimulatory social cues cannot override the inhibitory effects of an inadequate
      diet.

PMID- 1995862
TI  - 1,25-Dihydroxyvitamin D3 induces in vivo the decidualization of rat endometrial
      cells.
AB  - Intraluminal injection of female rats at Day 5 of pseudopregnancy with 10-500 ng
      1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) significantly increased the uterine
      weight and induced decidual reaction. This effect was observed as early as the
      3rd day after 1,25-(OH)2D3 injection. It was detectable only in the injected left
      horn and not in the non-injected right horn. A 500 ng dose of 25-(OH)D3 had no
      such effect. The present in-vivo results suggest that 1,25-(OH)2D3 may play a
      physiological role in endometrial cell differentiation into decidual cells, a
      crucial step in the process of blastocyst implantation.

PMID- 1995863
TI  - Relationship between sexual abstinence of men and chromosomally abnormal
      spermatozoa.
AB  - Epidemiological and mouse cytogenetic studies have suggested the existence of a
      positive relationship between the frequency of chromosomal abnormalities and the
      duration of male sexual abstinence. A cytogenetic analysis of human spermatozoa
      was performed with 4 men after periods of sexual abstinence ranging from 2 to 15
      days. Using hamster eggs for penetration, 934 sperm chromosome complements were
      obtained. The overall frequency of sperm chromosomal abnormalities was 9.4%.
      There was no correlation between the length of sexual abstinence and each type of
      chromosomal abnormality. Our results do not support the hypothesis of an
      increased risk of aberration with duration of abstinence.

PMID- 1995864
TI  - Absence of oxytocin-neurophysin messenger RNA in the day-18 bovine conceptus.
AB  - Total cellular RNA was isolated from conceptus tissue obtained from 22
      superovulated cows 18 days after artificial insemination. Total RNA was also
      isolated from luteal tissue from 3 cyclic cows 7 and 8 days after oestrus. Luteal
      and conceptus RNA were simultaneously subjected to formaldehyde-agarose gel
      electrophoresis and transferred to nitrocellulose by bidirectional diffusion
      blotting. Northern blots were probed using cDNAs specific for bovine oxytocin and
      bovine beta-actin gene sequences. Hybridization of the oxytocin cDNA to RNA was
      consistently observed on autoradiographs as a 0.6 kilobase (kb) band in lanes
      containing corpus luteum RNA, but was not detected in lanes containing conceptus
      RNA. The presence of conceptus RNA on the blots was confirmed by hybridization of
      the actin cDNA to conceptus RNA, which resulted in a 2.0 kb band on
      autoradiographs. These results suggest that oxytocin is not synthesized by the
      bovine conceptus on Day 18 of gestation.

PMID- 1995865
TI  - Decreased superovulatory responses in heifers superovulated in the presence of a
      dominant follicle.
AB  - Dairy heifers were superovulated in the presence (dominant group, N = 8) or
      absence (non-dominant group, N = 6) of a dominant follicle at the start of a a
      superovulatory treatment on Days 7-12 of the oestrous cycle (Day 0 = oestrus).
      Daily ultrasonographic observations of ovaries (recorded on videotape) starting
      on Day 3 were used to assess the presence or absence of a dominant follicle
      (diameter greater than 9 mm, in a growing phase or at a stable diameter for less
      than 4 days) and to monitor follicular development before and during treatment.
      The number of CL estimated by ultrasonography (7.1 +/- 1.8 vs 13.5 +/- 1.4) or by
      rectal palpation (6.9 +/- 2.0 vs 16.3 +/- 1.6) and mean progesterone
      concentrations (32.5 +/- 19 vs 80.7 +/- 16 ng/ml) after treatment were lower (P
      less than 0.01) in the dominant than in the non-dominant group. Based on number
      of CL, two populations of heifers were identified in the dominant group, i.e.
      those that had a high (dominant-high, N = 4; greater than 7 CL) or a low
      (dominant-low, N = 4; less than 7 CL) response to treatment. During treatment,
      the increases in number of follicles 7-10 mm and greater than 10 mm in diameter
      occurred sooner and were of higher magnitude in the non-dominant than in the
      dominant-high or dominant-low groups (P less than 0.01).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1995866
TI  - An association between chromosomal abnormalities in rapidly frozen 2-cell mouse
      embryos and the ice-forming properties of the cryoprotective solution.
AB  - This paper investigates the effect of straw handling on the viability of 2-cell
      mouse embryos rapidly frozen in dimethyl sulphoxide (DMSO) solutions. During the
      brief (3 min) equilibration step, straws were either rotated periodically to keep
      the embryos in suspension, or kept still to allow the embryos to settle onto the
      the inner surface of the straw. The effects of these straw movements were tested
      with cryoprotectant solutions containing 1.5, 3.0 or 4.5 M-DMSO. Rapidly cooled
      straws containing 4.5 M-DMSO vitrify throughout on cooling, but ice forms on
      warming. The survival and normality of embryos frozen in 4.5 M-DMSO was not
      influenced by straw handling as 91-92% formed blastocysts in vitro, 77-78% formed
      normal fetuses, and no chromosomal rearrangements were observed. In solutions
      containing less than 4.5 M-DMSO ice formation occurred throughout (1.5 M-DMSO),
      or in parts (3.0 M-DMSO) of the cryoprotectant during cooling. The viability of
      embryos frozen in 3.0 or 1.5 M-DMSO solutions was reduced both in vitro and in
      vivo and structural chromosome aberrations, predominantly tri- and quadri-radial
      rearrangements, were observed. The reduction in embryo viability, and the
      chromosomal damage was particularly pronounced in embryos frozen in 3.0 M-DMSO in
      straws which were rotated during the equilibration step (47% blastocysts, 15%
      fetuses, 77% chromosome rearrangements). The results indicate that rapid freezing
      of 2-cell mouse embryos in 4.5 M-DMSO is safe and efficient, whereas freezing at
      lower DMSO concentrations is associated with severe chromosome damage, and
      reduced viability in vitro and in vivo.

PMID- 1995867
TI  - Ovarian contents of immunoreactive beta-endorphin and alpha-N-acetylated opioid
      peptides in rats.
AB  - beta-Endorphin was measured by radioimmunoassay in homogenates of ovaries from
      immature Sprague-Dawley rats (21-29 days of age) and found to be present at
      levels of about 0.6-0.7 ng/ovary. After administration of PMSG there was
      approximately a 4-fold increase (2-3 ng/ovary) in total ovarian immunoreactive
      (ir) beta-endorphin 48 h after injection. Analysis of follicular fluid from
      similarly treated rats indicated about the same amount of ovarian ir-beta
      endorphin (2-3 ng/ovary) as in ovarian homogenates, suggesting that most of the
      ir-beta-endorphin is localized in follicular fluid of PMSG-primed immature rats.
      Immature rats were made pseudopregnant by administration of hCG 48 h after PMSG,
      and at 24 h after injection of hCG there was a slight, but significant and
      reproducible, increase in the ovarian content of ir-beta-endorphin. The serum
      concentration of ir-beta-endorphin was in the range of 1-3 ng/ml and was
      unaffected by PMSG and PMSG/hCG; likewise, the pituitary content of ir-beta
      endorphin did not change following administration of gonadotrophins to immature
      rats. In mature cyclic animals, levels of 2-4 ng ir-beta-endorphin/ovary were
      found, comparable to those in the ovaries of PMSG-primed immature rats, and there
      were only small changes during the oestrous cycle. In addition to ir-beta
      endorphin, we also obtained evidence for the presence of alpha-N-acetylated
      opioid peptides (endorphins or enkephalins) in the ovaries of PMSG-primed
      immature and mature rats. The physiological role of the opioid peptides in
      reproductive tissue is unknown, but they are presumably acting in an autocrine or
      paracrine fashion.

PMID- 1995868
TI  - The renewed potential for folate antagonists in contemporary cancer chemotherapy.

PMID- 1995869
TI  - Antineoplastic activity of didemnin congeners: nordidemnin and modified chain
      analogues.
AB  - Nordidemnin (2), a natural analogue of the marine cyclodepsipeptide didemnin B
      (1b), showed cytotoxic activity against L1210 leukemia and antineoplastic
      activity against P388 leukemia as well as B16 melanoma; nordidemnin (2) was as
      active as didemnin B (1b). The influence of synthetic modifications in the linear
      peptidic chain on in vitro and in vivo activity was also studied. Replacement of
      the terminal lactyl residue by mandelyl and 3-(p-hydroxyphenyl)propionyl residues
      in compounds 3 and 4, respectively, did not affect the cytotoxic activity against
      L1210 leukemia (ID50 of 1.1 nM and 1.2 nM, respectively) or the in vivo activity
      against P388 leukemia. Unlike these aromatic substituants, the lipophilic
      palmityl residue induced a dramatic loss in cytotoxic activity. The inverted
      chirality of the MeLeu joining residue in compound 6 caused a marked reduction in
      the in vitro activity.

PMID- 1995870
TI  - Potential antitumor agents. 62. Structure-activity relationships for tricyclic
      compounds related to the colon tumor active drug 9-oxo-9H-xanthene-4-acetic acid.
AB  - A series of tricyclic analogues of 9-oxo-9H-xanthene-4-acetic acid have been
      prepared and evaluated for their ability to cause hemorrhagic necrosis in
      subcutaneously implanted colon 38 tumors in mice, in an effort to extend the
      structure-activity relationships for this series. As was found previously with
      analogues of flavone-8-acetic acid (FAA) (Atwell et al. Anti-Cancer Drug Des.
      1989, 4, 161), all electronic modifications of the XAA nucleus led to severe
      decreases or complete abolition of activity, suggesting narrow structure-activity
      relationships. Dipole moments for many of the compounds were computed, and the
      degree to which the molecular dipole moment lay out of the plane of the aromatic
      part of these molecules was found to be determined largely by the contributions
      from the acetic acid moiety relative to that from the tricyclic ring system.
      There did not appear to be any general relationship between the magnitude of the
      dipole moment and activity. However, for compounds containing the 9-carbonyl
      functionality, the orientation of the dipole vector may be of significance. In
      all compounds possessing an ether group peri to the acetic acid side chain, there
      was a close approach (ca. 2.4 A) between this and the side chain OH.

PMID- 1995871
TI  - A 3-D model for 5-HT1A-receptor agonists based on stereoselective methyl
      substituted and conformationally restricted analogues of 8-hydroxy-2
      (dipropylamino)tetralin.
AB  - The enantiomers of cis- and trans-1,2,3,4,4a,5,10,10a-octahydro-9-hydroxy-1-
      propylbenzo[g]quinolines (10 and 11, respectively) and the enantiomers of trans
      1,2,3,4,4a,5,6,10b-octahydro-10- hydroxy-4-propylbenzo[f]quinoline (12) have been
      synthesized and their stereochemical and conformational characteristics have been
      studied by use of X-ray crystallography and molecular mechanics (MMP2)
      calculations. The compounds, which are conformationally restricted analogues of
      the potent 5-hydroxytryptamine (5-HT) receptor agonist 8-hydroxy-2-
      (dipropylamino)tetralin (8-OH-DPAT; 1) have been evaluated for central 5-HT and
      dopamine receptor stimulating activity by use of biochemical and behavioral tests
      in rats. In addition, we have evaluated the ability of these compounds and a
      number of previously reported analogues to displace [3H]-8-OH-DPAT from 5-HT1A
      binding sites. The enantiomers of 12 behave as potent 5-HT1A-receptor agonists,
      whereas the octahydrobenzo[g]quinoline derivatives are much less potent or
      inactive. In general, the affinities of the compounds correlate well with their
      agonist potencies. The set of compounds under study is accommodated by a novel
      computer-graphics-derived model for 5-HT1A-receptor agonism. The model consists
      of a flexible pharmacophore and a partial receptor-excluded volume.

PMID- 1995872
TI  - Molecular and crystal structures of MDL27,467A hydrochloride and quinapril
      hydrochloride, two ester derivatives of potent angiotensin converting enzyme
      inhibitors.
AB  - The molecular structures of MDL27,467A hydrochloride, [4 alpha,7 alpha(R*),12b
      beta]-7-[[1-(ethoxycarbonyl)-3-phenyl-propyl] amino]-1,2,3,4,6,7,12a,12b
      octahydro-6-oxopyrido[2,1- a][2]benzazepine-4-carboxylic acid diphenylmethyl
      ester hydrochloride, and quinapril hydrochloride, [3S-[2[R*(R*)],3R]]-2-[2[[1-
      (ethoxycarbonyl)-3-phenylpropyl]-amino]-1-oxopropyl]-1,2,3,4- tetrahydro-3
      isoquinolinecarboxylic acid hydrochloride, were determined by X-ray diffraction
      methods. The modified, C-terminal dipeptide portions and the phenylpropyl
      fragments in both crystal structures adopt similar conformations. The binding
      positions for several pharmacophores are defined by the constraint of the
      tricyclic system in the crystallographic structure of MDL27,467A hydrochloride.
      Conformational energy calculations show that the phenyl ring of the tetrahydro-3
      isoquinoline system of quinapril does not fit into the S2 hydrophobic pocket of
      angiotensin converting enzyme.

PMID- 1995873
TI  - Analysis of the in vitro antitumor activity of novel purine-6-sulfenamide, 
      sulfinamide, and -sulfonamide nucleosides and certain related compounds using a
      computer-aided receptor modeling procedure.
AB  - The comparative antileukemic activities of 21 novel nucleosides were determined
      in vitro by using cultured L1210 cells and analyzed for structure-related
      efficacy by a computer-aided receptor modeling method (REMOTEDISC) as recently
      described (Ghose, A. K.; et al. J. Med. Chem. 1989, 32, 746). The algorithm can
      be classified as a 3D-QSAR method and consists of the following steps: selection
      of a reference structure from the low-energy conformations of the active
      compounds; an automated superposition of the low-energy conformations of the
      other compounds so that there is maximum matching (or overlapping) of the atom
      based physicochemical properties; construction of the binding-site cavity from
      the location of the atoms of the superimposed molecules; and determinations of
      the relative importance of the various physicochemical properties at different
      regions of the site cavity using reverse stepwise regression analysis. The model
      was based on the minimum energy conformation of (R,S)-2-amino-9-beta-D
      ribofuranosylpurine-6-sulfinamide (sulfinosine, 5), an effective antileukemic
      agent in vivo, in the data set. The model fit the biological data with a standard
      deviation of 0.363, a correlation coefficient of 0.933 and a explained variance
      of 0.815. The method targeted a syn conformation as the probable active form and
      the 2'-OH, 5'-OH as well as C2-NH2 group of the purine ring as favoring the
      stability of the syn conformation, thereby establishing the major contributions
      of these three molecular entities to overall antitumor activity.

PMID- 1995874
TI  - Synthesis, peroxidating ability, and antineoplastic evaluation of 1
      [(aminoalkyl)amino]-4-hydroxy-10-imino-9-anthracenones.
AB  - A novel group of cytotoxic anthraquinone derivatives, 1-[(aminoalkyl)amino]-4
      hydroxy-10-imino-9-anthracenones, has been synthesized. It has been shown that
      imino analogues of the anthracenediones exhibit diminished ability to generate
      oxygen radicals. The cytotoxic activity of iminoanthracenones obtained was lower
      than that of the related quinone carbonyl analogues. One of the obtained imino
      compounds showed a moderate antileukemic activity in vivo.

PMID- 1995875
TI  - Synthesis and biological activity of bay-region metabolites of a cyclopenta-fused
      polycyclic aromatic hydrocarbon: benz[j]aceanthrylene.
AB  - The possibility of bay-region activation of the cyclopenta PAH (polycyclic
      aromatic hydrocarbon with a peripherally fused cyclopenta ring)
      benz[j]aceanthrylene (1) was investigated by synthesis and bioassay of the bay
      region metabolites trans-9,10-dihydroxy-9,10-dihydrobenz[j]aceanthrylene (4),
      trans-9,10-dihydroxy-anti-7,8-epoxy-7,8,9,10-tetrahydrobenz[j]a ceanthrylene (2),
      and 9,10-dihydrobenz[j]aceanthrylene 9,10-oxide (3). The known 1,2
      dihydrobenz[j]aceanthrylene-9,10-dione (5) was obtained by published methods;
      however, the direct route to target dihydrodiol 4, dehydrogenation of the
      saturated five-membered ring of 5 followed by NaBH4 reduction, gave a poor yield
      of 4 contaminated with tetrahydrogenated products. Acceptable yields of 4 were
      obtained by reduction of 5 to the corresponding tetrahydro diol, diacetylation of
      the diol, and dehydrogenation of the five-membered ring followed by base
      catalyzed deacetylation to 4. anti-Diol epoxide 2 was generated by m
      chloroperoxybenzoic acid oxidation of 4. Oxide 3 was synthesized by treatment of
      the monotosylate of 4 with NaOH in monoglyme. Diol epoxide 2 was an active
      mutagen in Salmonella typhimurium strain TA98 in the absence of metabolic
      activation, 3 showed marginal activity, while 3 and 4 were mutagenic with
      metabolic activation. These results coupled with previous studies support
      activation of benz[j]aceanthrylene via both 2 and cyclopenta ring epoxidation.

PMID- 1995876
TI  - 2,4-Diamino-5-benzylpyrimidines as antibacterial agents. 14. 2,3-Dihydro-1-(2,4
      diamino-5-pyrimidyl)-1H-indenes as conformationally restricted analogues of
      trimethoprim.
AB  - A conformationally restricted analogue of trimethoprim (1a) has been prepared by
      connecting the ortho position of the benzene ring to the methylene linkage with
      two methylene groups, thus forming a dihydroindene derivative (2b). The chemistry
      involved the condensation of barbituric acid with an indanone derivative,
      followed by a three-step conversion to a 2,4-diaminopyrimidine. The S isomer of
      2b was found to have a minimum-energy conformation very similar to that of 1a
      when bound to Escherichia coli dihydrofolate reductase, in contrast to that of 1a
      in vertebrate DHFR. Theoretically such a derivative might have increased
      specificity and activity against the bacterial enzyme. Molecular modeling
      experiments suggested that the actual decreased activity was due to crowding in
      the enzyme, caused by the extra atoms needed to restrict the conformation.

PMID- 1995877
TI  - Doxorubicin analogues incorporating chemically reactive substituents.
AB  - Doxorubicin (1) analogues 2-5, incorporating the following alkylating or latent
      alkylating substituents, R, on the 3'-position of the daunosamine sugar have been
      synthesized as potential antitumor agents: 2, R = NHCOC6H4(p)SO2F; 3, R =
      NHCOCH2Br; 4, R = NHCOCH2Cl; 5, R = NHCON(NO)CH2CH2Cl. These compounds were
      designed on the premise that alkylating anthracyclines might bind covalently to
      critical intracellular target macromolecules and overcome resistance to the
      parent agent attributable to reduced cellular drug accumulation. Growth
      inhibitory studies of the analogues were conducted in vitro against mouse
      leukemia cells (L1210 and P388) and human uterine sarcoma cells that are
      sensitive (MES-SA) and resistant (MES-SA/DOX) to doxorubicin. The analogues were
      5-100-fold less potent than doxorubicin against the sensitive cell lines.
      However, they were only marginally cross-resistant with doxorubicin against MES
      SA/DOX. Compounds 3 and 5 were also evaluated against a human myelocytic cell
      line (KBM-3) and a subline (KBM-3/DOX) resistant to doxorubicin. They were
      equally potent against both cell lines, indicating a complete lack of cross
      resistance with doxorubicin. Alkylating anthracyclines may have potential for the
      treatment of tumors resistant to the parent agents.

PMID- 1995878
TI  - 31P NMR and chloride ion kinetics of alkylating monoester phosphoramidates.
AB  - 31P NMR spectroscopy was used to study the solvolysis kinetics of a novel series
      of alkylating monoester phosphoramidates (4a-d) under model physiologic
      conditions. Halide ion kinetics were used to determine the rate of aziridinium
      ion formation. The solvolysis rates showed the expected dependence upon
      substitution at the reactive nitrogen; comparison of 4a with phosphoramide
      mustard (1a) indicated that replacement of the amino group by alkoxy decreased
      the solvolysis rate by approximately 10-fold. The rate of conversion of starting
      compound (4a-d) to solvolysis product was essentially equal to the rate of halide
      ion release, suggesting that the aziridinium ion is a short-lived intermediate.
      1H NMR and 31P NMR kinetics experiments performed in the absence and presence of
      trapping agent (dimethyldithiocarbamate) confirmed that the aziridinium ion was
      too short-lived to be observed via NMR. These compounds were also tested for
      cytotoxicity against L1210 leukemia and B16 melanoma cells in vitro; the
      monoalkylators 4c and 4d showed no activity, 4a was weakly cytotoxic, and 4b was
      comparable in activity to phosphoramide mustard.

PMID- 1995879
TI  - Antimalarial polyamine analogues.
AB  - A series of novel tetraamines of the general formula RNH(CH2)xNH(CH2)yNH(CH2)xNHR
      was synthesized and examined for activity against growth of Plasmodium falciparum
      in vitro. Within the series, dibenzyl analogues (R = benzyl) were found to be the
      most effective growth inhibitors, with IC50 values of about 10(-6) M. Further
      modifications of the tetraamine provided the optimum chain length for
      antimalarial activity of y = 7, x = 3. Compound 8 (MDL 27,695) with the structure
      y = 7, x = 3, R = benzyl, in combination with the ornithine decarboxylase
      inhibitor alpha-(difluoromethyl)ornithine, resulted in radical cures when tested
      against experimental Plasmodium berghei infections in mice. The structure
      activity relationships of the series are discussed.

PMID- 1995880
TI  - Synthesis and biological activity of methotrexate analogues with two acid groups
      and a hydrophobic aromatic ring in the side chain.
AB  - The heretofore unknown gamma-(m-carboxyanilide) and gamma-(m-boronoanillide)
      derivatives of methotrexate (MTX) and the gamma-(m-carboxyanilide) derivatives of
      aminopterin (AMT) were prepared and tested as inhibitors of dihydrofolate
      reductase (DHFR) and as inhibitors of cell growth in culture with the aim of
      comparing their activity with that of N alpha-(4-amino-4-deoxypteroyl)-N delta
      hemiphthaloyl-L-ornithine, a potent antifolate whose side chain likewise contains
      a hydrophobic aromatic ring with an acid group on the ring. All three anilides
      were potent DHFR inhibitors, with activity comparable to MTX and AMT. The gamma
      (m-boronoanilide) displayed growth inhibitory potency similar to that of the
      hemiphthaloylornithine analogue, with an IC50 of only 0.7 nM. This compound,
      which is the most potent of the gamma-amides of MTX tested to date, is also the
      first reported example of an antifolate with a B(OH)2 group in the side chain and
      is especially novel because of its potential to form a stable tetrahedral
      boronate complex by reaction with electron rich OH or NH2 groups in the active
      site of DHFR or other folate enzymes. In antitumor assays against L1210 leukemia
      in mice, N alpha-(4-amino-4-deoxypteroyl)-N delta-hemiphthaloyl-L-ornithine gave
      a T/C of greater than 263% at 20 mg/kg (qdx9) and 300% at 16 mg/kg (bidx10),
      whereas maximally tolerated doses of MTX of 8 mg/kg (qdx9) and 1 mg/kg (bidx10)
      gave T/C values of 213 and 188%, respectively. MTX gamma-(m-boronoanilide) was
      also active, with a T/C of 175% at 32 mg/kg (qdx9), the highest dose tested.

PMID- 1995881
TI  - Chemically stable, lipophilic prodrugs of phosphoramide mustard as potential
      anticancer agents.
AB  - Benzyl phosphoramide mustard (3), 2,4-difluorobenzyl phosphoramide mustard (4),
      and methyl phosphoramide mustard (5) were examined as lipophilic, chemically
      stable prodrugs of phosphoramide mustard (2). These phosphorodiamidic esters are
      designed to undergo biotransformation by hepatic microsomal enzymes to produce 2.
      The rate of formation of alkylating species, viz., 2, from these prodrugs and
      their in vitro cytotoxicity toward mouse embryo Balb/c 3T3 cells were comparable
      to or better than that of cyclophosphamide (1). Preliminary antitumor screening
      against L1210 leukemia in mice, however, suggests that these prodrugs are devoid
      of any significant antitumor activity in vivo.

PMID- 1995882
TI  - A new class of calcium antagonists. Synthesis and biological activity of 11
      [(omega-aminoalkanoyl)amino]-6,6a,7,8,9,10,10a,11-octahydrodibenzo [b,e]thiepin
      derivatives.
AB  - A series of 11-[(omega-aminoalkanoyl)amino]-6,6a,7,8,9,10,10a,11-
      octahydrodibenzo[b,e]thiepin derivatives were prepared and found to be a
      structurally new class of calcium antagonists. The structure-activity
      relationship studies indicated that the optimum was (6aR*,10aR*,11R*)-11-[[4-[4
      (4-fluorophenyl)-1- piperazinyl]butyryl] amino]-6,6a,7,8,9,10,10a,11
      octahydrodibenzo[b,e]thiepin (31,pA2 8.16), which was superior to diltiazem (pA2
      7.42) in calcium antagonistic activity. Compound 31 showed antihypertensive
      activity in anesthetized rats, without a significant effect on the heart rate. It
      had also antianginal effects in vasopressin-induced ST-depression and
      methacholine-induced ST-elevation testings in rats. These potencies of 31 were
      essentially equal to those of diltiazem.

PMID- 1995883
TI  - Synthesis and biological evaluation of 5-deazaisofolic acid, 5-deaza-5,6,7,8
      tetrahydroisofolic acid, and their N9-substituted analogues.
AB  - Prompted by recent disclosures concerning the potent antitumor activities of 5
      deaza-5,6,7,8-tetrahydrofolic acid and 5,10-dideaza-5,6,7,8-tetrahydrofolic acid
      (DDATHF), we have prepared 5-deazaisofolic acid (3a) and 5-deaza-5,6,7,8
      tetrahydroisofolic acid (4a). Reductive condensation of 2,6-diamino-3,4-dihydro-4
      oxopyrido[2,3-d]pyrimidine with di-tert-butyl N-(4-formylbenzoyl)-L-glutamate
      and subsequent deprotection with trifluoroacetic acid yielded 5-deazaisofolic
      acid in good yield. Catalytic hydrogenation of this analogue then gave 4a. The 9
      CH3 and 9-CHO modifications of 3a and the 9-CH3 derivative of 4a were also
      synthesized. Each of the new analogues was evaluated with a variety of folate
      requiring enzymes as well as MCF-7 cells in culture. Compound 4a had an IC50 of
      ca. 1 microM against MCF-7 cells and was nearly 100-fold less potent than DDATHF
      in this regard. The three oxidized isofolate analogues were all poor inhibitors
      of tumor cell growth.

PMID- 1995884
TI  - Synthesis and biological activity of 5,11-methylenetetrahydro-5- deazahomofolic
      acid.
AB  - The synthesis of 5,11-methylene-5-deazatetrahydrohomofolate (5), a stable,
      semirigid mimic of 5,10-methylenetetrahydrofolate (4) is reported as a potential
      inhibitor of thymidylate synthases (TS). The key intermediate 3-amino-1-oxo
      tetrahydropyrimido[4,5-c] [2,6]naphthyridine (6) was obtained by the
      regiospecific cyclocondensation of 2,4,6-triaminopyrimidine with ethyl 1-benzyl-3
      oxo-4-piperidinecarboxylate followed by halogenation (of the resulting lactam 9)
      and catalytic hydrogenolysis. Selective reduction of 6 followed by arylation with
      tert-butyl p-fluorobenzoate, saponification, and coupling with diethyl L
      glutamate followed by saponification afforded the target compound 5. The title
      compound was tested as an inhibitor of the growth of Manca human lymphoma cells
      and also as an inhibitor of TS from Manca cells and Lactobacillus casei and was
      found to be inactive. In addition, compound 5 also failed to inhibit glycinamide
      ribonucleotide formyltransferase from L. casei and from Manca cells.

PMID- 1995885
TI  - Novel benzamides as selective and potent gastrokinetic agents. 2. Synthesis and
      structure-activity relationships of 4-amino-5-chloro-2-ethoxy-N-[[4-(4
      fluorobenzyl)-2- morpholinyl]methyl] benzamide citrate (AS-4370) and related
      compounds.
AB  - The title compounds (19-55) with a 4-substituted 2-(aminomethyl)morpholine group
      were prepared and evaluated for the gastrokinetic activity by determining their
      effect on gastric emptying of phenol red semisolid meal in rats. Introduction of
      chloro, fluoro, and trifluoromethyl groups to the benzyl group of the parent
      compounds 1a and 1b enhanced the activity. Among compounds tested, 4-amino-5
      chloro-2-ethoxy-N-[[4-(4-fluorobenzyl)-2-morpholinyl] methyl] benzamide (23b)
      showed the most potent gastric emptying activity (effects on phenol red semisolid
      meal in rats and mice, and on resin pellets solid meal in rats). The
      gastrokinetic activity of 23b citrate (AS-4370) compared very favorably with that
      of cisapride and was higher than that of metoclopramide. In contrast to
      metoclopramide and cisapride, AS-4370 was free from dopamine D2 receptor
      antagonistic activity in both in vitro ([3H]spiperone binding) and in vivo
      (apomorphine-induced emesis in dogs) tests.

PMID- 1995886
TI  - Structure-activity relationship of quinazolinedione inhibitors of calcium
      independent phosphodiesterase.
AB  - A series of quinazolinediones and azaquinazolinediones is described which possess
      potent inhibitory activity toward the calcium-independent phosphodiesterase
      enzyme (CaIPDE). In vivo testing showed that this in vitro activity translates to
      animal models predictive of chronic diseases such as depression and inflammation.
      These results support the hypothesis that inhibition of CaIPDE may lead to useful
      activity in such chronic diseases.

PMID- 1995887
TI  - Renin inhibitory peptides. Incorporation of polar, hydrophilic end groups into an
      active renin inhibitory peptide template and their evaluation in a human renin
      infused rat model and in conscious sodium-depleted monkeys.
AB  - We previously reported that Boc-Pro-Phe-N-MeHis-Leu psi [CHOHCH2]-Ile-Amp (1) is
      a potent and specific inhibitor of human renin in vitro. It was shown to resist
      degradation by selected proteases and a rat liver homogenate. It was shown to
      inhibit plasma renin activity and to reduce blood pressure in renin-dependent
      animal models both by the intravenous and by the oral routes using dilute citric
      acid as vehicle. In an effort to discover compounds with improved pharmacological
      efficacy, we set out to modify the physical characteristics of this highly
      lipophilic renin inhibitor by incorporation of hydrophilic end groups. We report
      here a variety of water-solubilizing groups and the resulting structure-activity
      relationship of these compounds. They all maintain an extremely high level of
      enzyme inhibitory activity in vitro. Evaluation of these potent renin inhibitors
      in a human renin infused rat model suggests that some of these compounds exhibit
      improved pharmacological efficacy in vivo. This observation was further confirmed
      in the conscious sodium-depleted cynomolgus monkey. Importantly, the oral
      efficacy was demonstrated in a water vehicle in the absence of citric acid.

PMID- 1995888
TI  - Design of potent oxytocin antagonists featuring D-tryptophan at position 2.
AB  - We prepared nine analogues (1-9) of MCPA-D-Phe-Phe-Ile-Asn-Cys-Pro-Arg-Gly-NH2,
      [MCPA1, D-Phe2, Phe3, Ile4, Arg8]oxytocin (MCPA = beta-mercapto-beta,beta
      pentamethylenepropionic acid), a potent antagonist of the rat uterotonic action
      of oxytocin (OT). We replaced D-Phe with D-Trp and made [MCPA1,D
      Trp2,Phe3,Ile4,Arg8]OT (1), which had OT pA2 of 7.51, somewhat higher than that
      of the D-Phe2 antagonist which has OT pA2 = 7.35 in our rat uterotonic assay.
      Both compounds are equipotent as antagonists of [Arg8]vasopressin in the rat
      antidiuretic assay, with pA2 = 8.1. Other substitutions gave [MCPA1,D-Trp2,4-Cl
      Phe3,Ile4,Arg8]OT, (2), OT pA2 7.44; [MCPA1,D-Trp2,Phe3,Ile4,3,4-dehydro
      Pro7,Arg8]OT (3), OT pA2 = 7.42; [MCPA1,D-Trp2,Phe3,Arg8]OT (4), OT pA2 = 7.58;
      [MCPA1,D-Trp2,Phe3,Arg8,Gly9-NHEt]OT (5), OT pA2 = 7.49; [MCPA1,D
      Trp2,Ile4,Arg8]OT (6), OT pA2 = 7.46; [MCPA1,D-Trp2,Val4,Arg8]OT (7), OT pA2 =
      7.58; [MCPA1,D-Trp2,Thr4,Arg8]OT (8), OT pA2 = 7.48; and finally, [MCPA1,D
      Trp2,Arg8]OT (9), which was a more potent and more selective OT antagonist, with
      OT pA2 = 7.77 in the uterotonic assay and ADH pA2 less than 5.9 in the
      antidiuretic assay and hence is an important lead for the design of OT
      antagonists.

PMID- 1995889
TI  - 4',5'-unsaturated 5'-halogenated nucleosides. Mechanism-based and competitive
      inhibitors of S-adenosyl-L-homocysteine hydrolase.
AB  - The design and synthesis of (E)- and (Z)-5'-fluoro-4',5'-didehydro-5'
      deoxyadenosine (6 and 13, respectively), a new class of mechanism-based
      inhibitors of S-adenosyl-L-homocysteine (SAH) hydrolase, is described. A number
      of analogues of 6 and 13 were synthesized in order to determine the structure
      activity relationship necessary for inhibition of the enzyme. Substitution of
      chlorine for fluorine in 6 (i.e. 44), addition of an extra chlorine to the 5'
      vinyl position (i.e. 51 and 52), modification of the 2'-hydroxyl group to the
      deoxy (34 and 35) and arabino (36 and 37) nucleosides provided competitive
      inhibitors of SAH hydrolase. Nucleosides 6 and 13, as well as 5'-deoxy-5',5'
      difluoroadenosine (14) proved to be time-dependent inhibitors of SAH hydrolase.
      All three compounds are postulated to inhibit through the potent electrophile
      derived from oxidation of the 3'-hydroxyl of 6 or 13 to the ketone (i.e. 3 and/or
      the E-isomer). Consistent with the proposed mechanism of inactivation of SAH
      hydrolase by 6, 13, and 14 was the observation that incubation of purified rat
      liver SAH hydrolase with 6 resulted in release of 1 equiv of fluoride ion (by 19F
      NMR) and incubation with 14 resulted in release of 2 equiv of fluoride ion. The
      general synthetic route developed for the synthesis of the title nucleosides
      utilized the fluoro Pummerer reaction for the introduction of fluorine into the
      requisite precursors. Preliminary antiretroviral data from Moloney leukemia virus
      (MoLV) is presented and correlates with SAH hydrolase inhibition. Antiviral
      activity (IC50 against MoLV) ranged from 0.05 to 10 micrograms/mL.

PMID- 1995890
TI  - Quinolone antibacterials: preparation and activity of bridged bicyclic analogues
      of the C7-piperazine.
AB  - A series of quinolone and naphthyridine antibacterial agents possessing as the C7
      heterocycle bicyclic 2,5-diazabicyclo[n.2.m]alkanes, where n = 2, 3 and m = 1, 2,
      and a series including 4-aminopiperidine and 3-amino-8-azabicyclo[3.2.1]octanes
      have been prepared and evaluated in vitro and in vivo for antibacterial activity
      against a variety of Gram-negative and Gram-positive organisms. These compounds
      were also tested against the target enzyme bacterial DNA gyrase. All the examples
      investigated are nearly equipotent with the parent 7-piperazinyl analogues. Only
      endo-7-(3-amino-8-azabicyclo[3.2.1]oct-8-yl)-1-cyclopropyl-6,8-difluoro- 1,4-
      dihydro-4-oxo-3-quinolinecarboxylic acid displays activity that surpasses that of
      the piperazine parent.

PMID- 1995891
TI  - Configuration and preferential solid-state conformations of perindoprilat (S
      9780). Comparison with the crystal structures of other ACE inhibitors and
      conclusions related to structure-activity relationships.
AB  - The conformation of perindoprilat, an antihypertensive drug, is studied in the
      solid state by X-ray analysis. The resolution of its structure reveals important
      analogies between its observed conformation and that of several ACE inhibitors of
      the same family. This comparison points out a constant relative orientation of
      the functional groups, regardless of the molecular environment. This angular
      constancy appears to us as not being accidental and is a good argument for the
      spatial design of the ACE binding site. Although ACE is a carboxydipeptidase, the
      binding site may not contain two but one unique hydrophobic pocket receiving the
      C-terminal end of the inhibitors.

PMID- 1995892
TI  - Synthesis of halogen-substituted 1,5-benzothiazepine derivatives and their
      vasodilating and hypotensive activities.
AB  - In an attempt to improve the effectiveness and duration of the action of
      diltiazem (1), a 1,5-benzothiazepine calcium channel blocker, its derivatives (2)
      with halogen substituents on the fused benzene ring were synthesized. These
      compounds were evaluated for their effects on vertebral and coronary blood flows
      and antihypertensive activity. The structure-activity relationships are
      discussed. The 8-chloro derivative ((+)-2b), the most potent compound in this
      series, was selected for clinical evaluation as a cerebral vasodilating and
      antihypertensive agent.

PMID- 1995893
TI  - Muscarinic cholinergic agonists and antagonists of the 3-(3-alkyl-1,2,4-oxadiazol
      5-yl)-1,2,5,6-tetrahydropyridine type. Synthesis and structure-activity
      relationships.
AB  - A series of 3-(3-alkyl-1,2,4-oxadiazol-5-yl)-1,2,5,6-tetrahydro-1-methylpyr
      idines (2a-q) were synthesized and tested for central muscarinic cholinergic
      receptor binding affinity by using [3H]oxotremorine-M and [3H]QNB as ligands and
      in a functional assay using guinea pig ileum. The analogues with unbranched C1-8
      alkyl substituents (2a-g) were agonists, whereas the compounds with branched or
      cyclic substituents (2h-m) were antagonists. The alkyl ether analogues (2o-q)
      were also agonists but had lower receptor binding affinity than the corresponding
      alkyl analogues. The 3-(5-alkyl-1,2,4-oxadiazol-3-yl)-1,2,5,6-tetrahydro-1
      methylpyridi ne analogues had only ver low affinity for the central muscarinic
      receptors and were weak antagonists in the ileum assay. A few 3-(3-butyl-1,2,4
      oxadiazol-5-yl)-1,2,5,6-tetrahydro-1-methylpyr idines substituted with methyl or
      hydrogen in the 1-, 5-, or 6-position were synthesized and tested. N-Desmethyl
      analogue 7 was a potent muscarinic agonist, whereas N-desmethyl-5-methyl analogue
      11 and N-methyl-6-methyl analogue 13 both were antagonists with lower muscarinic
      receptor affinity. The 3-(3-butyl-1,2,4-oxadiazol-5-yl)quinuclidine (17) and
      tropane (15) analogues were both very potent antagonists with high affinity for
      central muscarinic receptors. The ratio [IC50(QNB)/IC50(Oxo-M)] x 0.162 proved to
      be a good indicator of the efficacy of the compounds in the guinea pig ileum
      assay.

PMID- 1995894
TI  - Synthesis and anticancer activity of various 3'-deoxy pyrimidine nucleoside
      analogues and crystal structure of 1-(3-deoxy-beta-D-threo
      pentofuranosyl)cytosine.
AB  - Various 3'-deoxy pyrimidine nucleoside analogues have been synthesized for
      evaluation as potential anticancer and antiviral agents. Among these compounds, 1
      (3-deoxy-beta-D-threo-pentofuranosyl)cytosine (10, 3'-deoxy-ara-C) and 3'
      deoxycytidine (22) had significant anticancer activity against CCRF-CEM, L1210,
      P388, and S-180 cancer cell lines in vitro, producing ED50 values of 2, 10, 5,
      and 34 microM, respectively, for 3'-deoxy-ara-C (10); and 25, 5, 2.5, and 15
      microM, respectively, for 3'-deoxycytidine (22). Thus, 3'-deoxy-ara-C (10) was
      12.5 times more active against CCRF-CEM cells than 3'-deoxycytidine (22). The 2'
      O-acetyl, 5'-O-acetyl, and 2',5'-di-O-acetyl derivatives of 3'-deoxy-ara-C (10),
      compounds 34, 31, and 30, demonstrated anticancer activity in the same range as
      3'-deoxy-ara-C (10) against CCRF-CEM, L1210, P388, and S-180 cells. The 5'-O
      acetyl derivative (31) had significantly greater activity against CCRF-CEM with
      an ED50 value of 0.4, but this compound also showed similar activity, as did 3'
      deoxy-ara-C, against L1210, P388, and S-180 with ED50 values of 3, 3, and 13
      microM, respectively. 3'-Deoxy-ara-C was also evaluated in vitro against HSV-2,
      HCMV, and GPCMV viruses and was found to be not very active with respective IC50
      values of 110, 220, and 1000 microM. The single-crystal structure of 3'-deoxy-ara
      C (10) was determined by X-ray crystallography. There are two molecules of the
      nucleoside and one molecule of water in the asymmetric unit. The sugar moieties
      of the two nucleoside molecules adopt different conformations. In molecule A, the
      ring pucker is C3'-endo with P = 18.7 degrees and tau m = 37.3 degrees, while the
      CH2OH side chain is gauche+. In molecule B, the ring pucker is C2'-endo with P =
      156.8 degrees and tau m = 37.8 degrees and the side chain is trans.

PMID- 1995895
TI  - Synthesis of 3-carbamoylecgonine methyl ester analogues as inhibitors of cocaine
      binding and dopamine uptake.
AB  - Five (1R-2-exo-3-exo)-3-(N-phenylcarbamoyl)ecgonine methyl ester analogues were
      synthesized and characterized by 1H and 13C NMR, IR, and thermospray MS. The
      compounds were synthesized in two or three steps as (-)-stereoisomers from (-)
      ecgonine in good yield (56% overall). These cocaine derivatives were assessed for
      their ability to inhibit [3H]cocaine binding to rat striatal tissue and to
      inhibit [3H]dopamine uptake into synaptosomes prepared from the same tissue. The
      most potent of the analogues was (1R-2-exo-3-exo)-2-(carbomethoxy)-8-methyl-8
      azabicyclo[3.2.1]octyl 3-N-(3'-nitrophenyl)carbamate. IC50 values for inhibition
      of cocaine binding and dopamine uptake were 37 and 178 nM, respectively. Amino
      derivatives were less active than the nitro and (1R-2-exo-3-exo)-2-(carbomethoxy)
      8-methyl-8-azabicyclo [3.2.1]octyl 3-N-(4'-aminophenyl)carbamate had the lowest
      affinity for the receptor with IC50 values of 63 and greater than 100 microM in
      the aforementioned assays, respectively.

PMID- 1995896
TI  - Synthesis and anti-HIV-1 activity of 4,5,6,7-tetrahydro-5-methylimidazo[4,5,1
      jk][1,4]benzodiazepin- 2(1H)-one (TIBO) derivatives.
AB  - A series of 6-substituted 4,5,6,7-tetrahydro-5-methylimidazo[4,5,1
      jk][1,4]benzodiazepin- 2(1H)-ones (9) have been synthesized and tested for their
      ability to inhibit the replication of the HIV-1 virus in MT-4 cells. Two
      synthetic methods are described, one of which allows the synthesis of single
      enantiomers of the final products. A structure-activity study was done within the
      series of compounds to determine the optimum group for the 6-position
      substitution and to determine whether the activity was enantiospecific at the 5
      position, which was substituted with a methyl group. The best analogue, 9jj,
      inhibited HIV-1 with an IC50 of 4 microM, which is comparable to the activity
      level of DDI, a 2',3'-dideoxynucleoside-type structure undergoing clinical trials
      as an anti-AIDS therapy.

PMID- 1995897
TI  - Allosteric modifiers of hemoglobin. 1. Design, synthesis, testing, and structure
      allosteric activity relationship of novel hemoglobin oxygen affinity decreasing
      agents.
AB  - Three isomeric series of 2-(aryloxy)-2-methylpropionic acids were prepared and
      studied for their ability to decrease the oxygen affinity of human hemoglobin A.
      The isomeric aryloxy groups included 4-[[(aryloyl)amino]methyl]phenoxy, 4
      (arylacetamido)phenoxy, and 4-[[(arylamino)carbonyl]methyl]phenoxy. A total of 20
      compounds were synthesized and tested. Structure-activity relationships are
      presented. Several of the new compounds were found to be strong allosteric
      effectors of hemoglobin. The two most active compounds are 2-[4-[[(3,5
      dichloroanilino)carbonyl]-methyl]phenoxy]- 2-methylpropionic acid and the
      corresponding 3,5-dimethyl derivative. The latter two compounds have been
      compared to other known potent allosteric effectors in the same assay and show
      greater activity. Both compounds also exhibit a right shift in the oxygen
      equilibrium curve when incubated with whole blood. The new compounds may be of
      interest in clinical or biological areas that require or would benefit from a
      reversal of depleted oxygen supply (i.e., ischemia, stroke, tumor radiotherapy,
      blood storage, blood substitutes, etc.). They are also structurally related to
      several marketed antilipidemic agents.

PMID- 1995898
TI  - Allosteric modifiers of hemoglobin. 2. Crystallographically determined binding
      sites and hydrophobic binding/interaction analysis of novel hemoglobin oxygen
      effectors.
AB  - The protein-bound conformations of six new allosteric effectors similar to
      bezafibrate that markedly decrease the oxygen affinity of hemoglobin have been
      determined by X-ray crystallography. Comparisons are made with the bound
      conformations of three urea analogues reported by Lalezari, Perutz, and co
      workers. All six new molecules bind at the same site previously observed for
      bezafibrate and exhibit a wide range of allosteric activity. Unlike the urea
      derivatives, which show two binding sites for the most potent derivatives, only
      one of the six new molecules (one with moderate allosteric activity) exhibits a
      second binding site. A new computer program, HINT (hydrophobic interactions), has
      been created and utilized to identify the major interactions between small
      molecules and the protein. The three strongest interactions identified by HINT
      involve Arg 141 alpha with the acid of the analogues, Lys 99 alpha with the
      bridging amide carbonyl, and the amide NH of the side chain of Asn 108 beta with
      the halogenated aromatic ring.

PMID- 1995899
TI  - Synthesis of high specific activity (+)- and (-)-6-[18F]fluoronorepinephrine via
      the nucleophilic aromatic substitution reaction.
AB  - The first example of a no-carrier-added 18F-labeled catecholamine, 6
      [18F]fluoronorepinephrine (6-[18F]FNE), has been synthesized via nucleophilic
      aromatic substitution. The racemic mixture was resolved on a chiral HPLC column
      to obtain pure samples of (-)-6-[18F]FNE and (+)6-[18F]FNE. Radiochemical yields
      of 20% at the end of bombardment (EOB) for the racemic mixture (synthesis time 93
      min), 6% for each enantiomer (synthesis time 128 min) with a specific activity of
      2-5 Ci/mumol at EOB were obtained. Chiral HPLC peak assignment for the resolved
      enantiomers was achieved by using two independent methods: polarimetric
      determination and reaction with dopamine beta-hydroxylase. Positron emission
      tomography (PET) studies with racemic 6-[18F]FNE show high uptake and retention
      in the baboon heart. This work demonstrates that nucleophilic aromatic
      substitution by [18F]fluoride ion is applicable to systems having electron-rich
      aromatic rings, leading to high specific activity radiopharmaceuticals.
      Furthermore, the suitably protected dihydroxynitrobenzaldehyde 1 may serve as a
      useful synthetic precursor for the radiosynthesis of other complex 18F-labeled
      radiotracers.

PMID- 1995900
TI  - Romazarit: a potential disease-modifying antirheumatic drug.
AB  - The synthesis of a series of substituted heterocyclic alkoxypropionic acids is
      described. They were evaluated for antiinflammatory effects in two animal models
      of chronic inflammation; adjuvant arthritis and type II collagen arthritis in the
      rat. The desired profile of biological activity was characterized by the
      reduction of inflammation with the coincident restoration toward normal levels of
      the biochemical markers (acute phase proteins) associated with the inflammatory
      response, an effect that was not shared by classical nonsteroidal
      antiinflammatory agents. Romazarit, (Ro 31-3948, 7), 2-[[2-(4-chlorophenyl)-4
      methyl-5-oxazolyl]methoxy]-2-methylpropio nic acid, was selected for further
      evaluation. In contrast to NSAIDs, romazarit was inactive in animal models of
      acute inflammation, and furthermore it did not inhibit the cyclooxygenase enzyme
      in vitro or in vivo. Inhibition of interleukin-1-mediated events in vitro has
      been observed.

PMID- 1995901
TI  - Nucleosides and nucleotides. 96. Synthesis and antitumor activity of 5-ethynyl-1
      beta-D-ribofuranosylimidazole-4-carboxamide (EICAR) and its derivatives.
AB  - The palladium-catalyzed cross-coupling reaction of 5-iodo-1-(2,3,5-tri-O-acetyl
      beta-D-ribofuranosyl)imidazole-4- carboxamide (8) with various terminal alkynes
      in the presence of bis(benzonitrile)palladium dichloride in acetonitrile
      containing triethylamine gave the desired 5-alkynyl derivatives 9 in high yields.
      However, when (trimethylsilyl)acetylene was used, the only isolable product was
      the undesired dimer, 1,2-bis(4-carbamoyl-1-beta-D-ribofuranosylimidazol-5
      yl)acetylene derivative 10a. To circumvent such dimer formation, the reaction was
      done with use of trimethyl-[(tributylstannyl)ethynyl]silane in the absence of
      triethylamine to afford the desired 5-(2-trimethylsilyl)ethynyl derivative 9a in
      good yield. Furthermore, the similar cross-coupling reaction of 5-iodo-1-(2,3,5
      tri-O-acetyl-beta-D-ribofuranosyl)imidazole-4-carboni tri le (12) with
      (trimethylsilyl)acetylene also afforded the desired nucleoside 13a. Deprotection
      of these compounds furnished 5-alkynyl-1-beta-D-ribofuranosylimidazole-4
      carboxamides (6b-k) and -carbonitriles (14b-f). Among these, 5-ethynyl-1-beta-D
      ribofuranosylimidazole-4-carboxamide (6b, EICAR) is the most potent inhibitor of
      growth of the various tumor cells in culture including human solid tumor cells.
      Preliminary results of in vivo antitumor activity against murine leukemias L1210
      and P388 are also described.

PMID- 1995902
TI  - Structure-activity relationship of mutagenic aromatic and heteroaromatic nitro
      compounds. Correlation with molecular orbital energies and hydrophobicity.
AB  - A review of the literature yielded data on over 200 aromatic and heteroaromatic
      nitro compounds tested for mutagenicity in the Ames test using S. typhimurium
      TA98. From the data, a quantitative structure-activity relationship (QSAR) has
      been derived for 188 congeners. The main determinants of mutagenicity are the
      hydrophobicity (modeled by octanol/water partition coefficients) and the energies
      of the lowest unoccupied molecular orbitals calculated using the AM1 method. It
      is also shown that chemicals possessing three or more fused rings possess much
      greater mutagenic potency than compounds with one or two fused rings. Since the
      QSAR is based on a very wide range in structural variation, aromatic rings from
      benzene to coronene are included as well as many different types of heterocycles,
      it is a significant step toward a predictive toxicology of value in the design of
      less mutagenic bioactive compounds.

PMID- 1995903
TI  - Synthesis and protein-tyrosine kinase inhibitory activities of flavonoid
      analogues.
AB  - Treatment of o-hydroxyacetophenones 2a-e with excess lithium
      bis(trimethylsilyl)amide followed by dialkyl carbonates gave alkyl 3-(2
      hydroxyaryl)-3-oxopropanoates 3a-e. The latter substances were transformed
      through the reaction of their magnesium chelates with benzoyl chlorides into a
      series of 3-(alkoxycarbonyl)-2-arylflavones, which were subsequently elaborated
      into a variety of flavonoids. These compounds were tested for their abilities to
      inhibit the in vitro protein-tyrosine kinase activity of p56lck, an enzyme which
      is thought to play a key role in mediating signal transduction from the CD4
      receptor during lymphocyte activation. All of the active compounds had either an
      amino or a hydroxyl substituent at the 4'-position of the 2-aryl ring. The most
      active substance prepared in this study is compound 17c, which is approximately 1
      order of magnitude more potent than the natural product quercetin (1). Compound
      17c was a competitive inhibitor of p56lck with respect to ATP and was highly
      selective for the inhibition of protein-tyrosine over protein-serine/threonine
      kinases.

PMID- 1995904
TI  - Dihydropyrimidine calcium channel blockers. 3. 3-Carbamoyl-4-aryl-1,2,3,4
      tetrahydro-6-methyl-5-pyrimidinecarboxylic acid esters as orally effective
      antihypertensive agents.
AB  - In order to explain the potent antihypertensive activity of the modestly active
      (IC50 = 3.2 microM) dihydropyrimidine calcium channel blocker 5, we carried out
      drug metabolism studies in the rat and found 5 is metabolized to compounds 6-10.
      Two of the metabolites, 6 (IC50 = 16 nM) and 7 (IC50 = 12 nM), were found to be
      responsible for the antihypertensive activity of compound 5. Potential metabolism
      of 6 into 7 in vivo precluded our interest in pursuing compounds related to 6.
      Structure-activity studies aimed at identifying additional aryl-substituted
      analogues of 7 led to 17g,j,p with comparable potential in vivo, though these
      compounds were less potent than 7 in vitro. To investigate the effects of
      absolute stereochemistry on potency, we resolved 7 via diastereomeric ureas
      19a,b, prepared from 18 by treatment with (R)-alpha-methylbenzylamine. Our
      results demonstrate that the active R-(-)-enantiomer 20a of 7 is both more potent
      and longer acting than nifedipine (1) as an antihypertensive agent in the SHR.
      The in vivo potency and duration of 20a is comparable to the long-acting
      dihydropyridine amlodipine. The superior oral antihypertensive activity of 20a
      compared to that of previously described carbamates 2 (R2 = COOEt) could be
      explained by its improved oral bioavailability, possibly resulting from increased
      stability of the urea functionality.

PMID- 1995905
TI  - Nucleosides and nucleotides. 97. Synthesis of new broad spectrum antineoplastic
      nucleosides, 2'-deoxy-2'-methylidenecytidine (DMDC) and its derivatives.
AB  - A new type of antineoplastic nucleoside, 2'-deoxy-2'-methylidenecytidine (DMDC)
      has been synthesized from the corresponding 2'-keto pyrimidine nucleosides 3 and
      8 by the Wittig reaction. During the course of the reaction, we found that an
      intermediate betaine could pick a proton from the excess triphenylphosphonium
      bromide to form the 2'-phosphonium salts 5 and 10, which could be further
      converted into the 2'-deoxy-2'-methylidene nucleosides 4 and 9 by treatment with
      sodium hydride. Various 5-substituted DMDC derivatives 19a-e,h and their uracil
      congeners 16a-h were also synthesized from the corresponding 5-substituted
      uridines 12a-f,h. Among them, DMDC as well as 2'-deoxy-2'-methylidene-5
      fluorocytidine (19a) showed potent antileukemic activity against murine L1210
      cells in culture. The activity of DMDC and 19a toward various human tumor cells
      in culture compared with 1-beta-D-arabinofuranosylcytosine and 5-fluorouracil was
      also examined. In vivo antitumor activity of DMDC against L1210 was also
      described.

PMID- 1995906
TI  - Structure-stability relationships of Gd(III) ion complexes for magnetic resonance
      imaging.
AB  - Molecular mechanical calculations and molecular dynamics simulations, based on
      the AMBER force field, were used to examine the molecular structures and
      stabilities of nine multidentate ligands and their Gd(III) ion complexes. The
      magnitude of various factors determining the stability of multidentate Gd(III)
      complexes, including the energy loss due to change of ligand conformation by
      complexation, the energy gain from cation-ligand attraction, and effects of
      intramolecular hydrogen bonding, were calculated by molecular mechanics. The fit
      between the Gd cation and the binding cavity in the ligands was examined by
      molecular graphics techniques. Intramolecular hydrogen bonds in free ligands with
      amide or hydroxyl as H-bond donors usually disfavor complex formation, due to
      disruption of hydrogen bonds during complex formation. Intramolecular hydrogen
      bonds may contribute to enhance complex stability if they make the desolvation
      energy of the free ligands smaller. The calculated complex stabilities were in
      reasonable agreement with experimental log K values which were available for five
      of the compounds. The calculated complex stabilities of two hitherto
      unsynthesized covalently constrained DTPA-derivatives and a DOTA-derivative
      bearing phenoxy groups as pendant arms indicate that these may form Gd(III)
      complexes with sufficient stability for use in magnetic resonance imaging
      techniques.

PMID- 1995907
TI  - Synthesis and biological evaluation of a series of 1,1-dichloro-2,2,3
      triarylcyclopropanes as pure antiestrogens.
AB  - A series of 1,1-dichloro-2,2,3-triarylcyclopropanes (DTACs) was synthesized and
      evaluated as pure antiestrogens. Addition of 4-methoxy- or 4-(benzyloxy)phenyl
      Grignard reagents to p-methoxy, p-benzyloxy, or unsubstituted deoxybenzoins,
      followed by dehydration of the resulting carbinols produced a mixture of E and Z
      olefins, which were reacted with dichlorocarbene to give O-protected DTACs. The E
      and Z isomers were separated by fractional crystallization and the central or
      geminal phenyl ring was deprotected to provide phenolic DTACs. Alkylation with
      (N,N-dimethylamino)ethyl chloride yielded basic cyclopropanes. Two
      chlorodiarylindenes were isolated as thermolysis products of the DTACs, and one
      was converted to a phenol by hydrogenolysis. All DTACs and indenes were
      competitive inhibitors of [3H]estradiol binding in the immature rat uterine
      cytosol receptor assay, with relative binding affinities of 0.1-3.6% of
      estradiol. None of the new compounds were estrogenic in the 3-day immature mouse
      uterotrophic assay at doses up to 750 micrograms. In the 3-day immature mouse
      antiuterotrophic assay, five DTACs with either a methoxy (5a), benzyloxy (4d,
      5c), or (dimethylamino)ethoxy (7a, 7b) central ring side chain produced
      significant decreases in uterine weight at doses up to 750 micrograms. One
      compound, (Z)-1,1-dichloro-2-[4-[2-(dimethylamino)ethoxy]-phenyl]-2-(4-
      methoxyphenyl)-3-phenylcyclopropane (7b), elicited a dose-dependent decrease in
      vivo comparable to MER 25. These same five compounds, as well as the lead
      compound Analog II, were active in vitro against the estrogen-dependent MCF-7
      human breast tumor cell line in a dose-dependent fashion.

PMID- 1995908
TI  - Synthesis and biological activity of D3-trishomocubyl-4-amines.
AB  - The D3-trishomocubyl system was prepared from tertiary
      pentacyclo[5.4.0.0(2,6).0(3,10).0(5,9)]undecan-8-ols 5 in one step by using a
      modified Ritter reaction yielding only one of the possible two geometrical
      isomers of 4-amino-3-alkyl (or aryl)-D3-trishomocubane (8). Promising antagonism
      of reserpine-induced catalepsy was exhibited by these compounds which compared
      favorable with that of amantadine. Weak to mild anticholinergic properties were
      observed during the reduction of oxotremorine induced tremor and salivation
      procedure. Acute toxicities similar to that of amantadine were observed for some
      of these compounds. D3-Trishomocubyl-4-amines appeared as a promising new class
      of anti-Parkinson agents.

PMID- 1995909
TI  - Synthesis, receptor binding, and tissue distribution of 7 alpha- and 11 beta
      substituted (17 alpha,20E)- and (17 alpha,20Z)-21-[125I]iodo-19-norpregna
      1,3,5(10),20-tetraene-3,17-diols.
AB  - The 11 beta-methoxy, 11 beta-ethoxy, and 7 alpha-methyl derivatives of the
      isomeric (17 alpha,20E)- and (17 alpha,20Z)-(iodovinyl)estradiols 3 and 6, and
      their no-carrier-added [125I]iodovinyl analogues, were evaluated for their
      relative target-tissue retention and binding affinity for the estrogen receptor.
      The isomeric iodovinyl and [125I]iodovinyl derivatives were prepared via
      destannylation of the corresponding tributylstannyl precursors in the presence of
      H2O2 or chloramine-T, with retention of configuration. The 20Z isomers 6
      exhibited slightly higher receptor binding affinities than the 20E isomers 3,
      with all eight isomeric products giving relative binding affinity values in the
      20-50 range. The 11 beta- and 7 alpha-substituted (iodovinyl)estradiols gave
      substantially higher estrogen receptor-mediated uterus uptake as compared to the
      nonsubstituted parent molecule. Synergism between the effect of 11 beta- or 7
      alpha-substituents and the configuration of the iodovinyl group was evident from
      the in vivo distribution pattern of [125I]-3 and -6. The best uterus uptake was
      observed, at 2 h postinjection, with the 20E isomer of 11 beta-methoxy derivative
      3b. However, at 5 h postinjection the 20Z isomer 6b reached higher uterus
      concentrations than the 20E isomer 3b, and furthermore, these values are now
      comparable to those observed with the 20Z isomer of the 11 beta-ethoxy derivative
      6c. In the case of the 7 alpha-methyl derivatives the differences in in vivo
      stability between the 20E and 20Z isomers was less pronounced, whereas the 20Z
      isomer 6d reached somewhat higher uterus to blood as well as nontarget ratios.

PMID- 1995910
TI  - Synthesis of high specific activity 6-[18F]fluorodopamine for positron emission
      tomography studies of sympathetic nervous tissue.

PMID- 1995911
TI  - Hydrophobicity parameters for platinum complexes.

PMID- 1995912
TI  - Genetic analysis and midline malignancies of uncertain origin.

PMID- 1995913
TI  - National Cancer Program created network for delivering research results.

PMID- 1995914
TI  - Women's Health Trial on trial.

PMID- 1995915
TI  - Kidney patients poll experts, fight for approval of interleukin-2.

PMID- 1995916
TI  - Fast food chains move toward healthier choices.

PMID- 1995917
TI  - A cohort study of fat intake and risk of breast cancer.
AB  - Between 1982 and 1987, 519 newly incident, histologically confirmed cases of
      breast cancer were identified in a cohort of 56,837 women enrolled in the
      Canadian National Breast Screening Study. These women had completed a dietary
      questionnaire before the occurrence of their breast cancer, and this has been
      used to estimate their intake of dietary fat and several other nutrients. There
      is evidence of a positive association between breast cancer and total fat intake,
      with a relative risk of 1.35 (95% confidence interval, 1.00-1.82) per 77 g per
      day, and some evidence of a dose-response relationship (P = .052).

PMID- 1995918
TI  - Disseminated human malignant melanoma in congenitally immune-deficient
      (bg/nu/xid) mice.
AB  - Congenitally immune-deficient bg/nu/xid (BNX) mice are severely compromised in
      their ability to mount T-cell, B-cell, and lymphokine-activated killer (LAK) cell
      responses. Successful engraftment of BNX mice with human hematopoietic stem cells
      has been demonstrated recently. We have investigated the potential use of BNX
      mice for studies relating to the biology and immunotherapy of human malignant
      melanoma. The intravenous injection of fresh single-cell suspensions of human
      malignant melanomas into mice resulted in widely disseminated disease. Metastatic
      spread of human melanoma in BNX mice mimicked that observed in patients: eg,
      there were numerous tumor nodules identified in the subcutaneous tissues as well
      as in a variety of visceral organs, including spleen, kidneys, thyroid, adrenals,
      lungs, heart, and brain. BNX mouse lymph nodes were replaced consistently by
      human malignant melanoma cells. The presence of human tumor cells in these mice
      was confirmed by histologic analysis and microcytofluorometry analyses using
      human melanoma-specific monoclonal antibodies (MAbs). Moreover, human melanoma
      cells passaged in BNX mice remained lysable in vitro by specifically cytolytic,
      autologous human tumor-infiltrating lymphocytes (TILs). The capacity of fresh
      human malignant melanoma to disseminate widely in BNX mice may prove valuable not
      only for study of the biology of metastatic spread but also for studies of the
      immunotherapy of human melanoma using melanoma-specific MAbs and chemotherapeutic
      agents, as well as human TILs and LAK cells with or without retrovirus-mediated
      gene transfer modification.

PMID- 1995919
TI  - Obesity and colorectal adenomatous polyps.
AB  - Obesity has been investigated as a risk factor for various malignancies,
      including colon cancer. A case-control study was conducted on patients in three
      colonoscopy practices in New York City to determine possible risk factors for
      colorectal adenomatous polyps, a known precursor lesion for most cases of
      colorectal cancer. Among 301 case subjects with incidence adenomatous polyps (174
      men and 127 women) and 506 control subjects (223 men and 283 women), an increased
      risk was observed with increasing body mass index in women (odds ratio 2.1, 95%
      confidence interval 1.1-4.0; for highest versus lowest quartile, linear trend P =
      .02). A nonsignificant trend was observed for men. The increased risk seen in
      women is consistent with prior observations regarding reproductive hormonal and
      dietary risk factors for colorectal cancer.

PMID- 1995921
TI  - Cells, research, and informed consent.

PMID- 1995920
TI  - Incidence rates of lymphomas and soft-tissue sarcomas and environmental
      measurements of phenoxy herbicides.

PMID- 1995922
TI  - Declining rates of lung cancer in the United States in young men and women.

PMID- 1995923
TI  - Model for assessment of lead content in human surface enamel.
AB  - Acid etch surface enamel microbiopsies were taken in vitro and in vivo and
      analyzed for lead using electrothermal atomic absorption spectrometry. The in
      vitro samples were obtained from subjects resident in an urbanized region in
      Belgium or from a region close to a nonferrometal industrial plant. The smaller
      set of in vivo samples were all from subjects resident in an urbanized region.
      Using a regression tree approach it was possible to identify in a stepwise manner
      factors that contributed to the variation of lead in the samples. For the in
      vitro as well as in vivo samples, the etch depth, tooth type, and age of the
      subjects were identified as significant factors but sex and dental arch quadrant
      were not. The residual lead levels obtained after regression with the significant
      factors were better distributed with much lesser variance. Moreover, a
      significant higher lead concentration could be demonstrated in the in vitro
      samples from the region close to the nonferrometal industrial plant.

PMID- 1995924
TI  - Hypothermic effects of a homologous series of short-chain alcohols in rats.
AB  - The purpose of this study was to assess the utility of the thermoregulatory
      system as an end point in predicting the toxicity of various short-chain
      alcohols. Male Fischer rats developed significant hypothermia following acute
      administration (ip) of methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, or 2
      butanol. The hypothermic responses to the six alcohols all showed similar
      segmented responses characterized by a threshold dose below which no change in
      body temperature occurred, and a suprathreshold regression with increasing dose
      causing greater hypothermia. Relative potency of the alcohols was assessed using
      both the threshold dose to cause hypothermia and the dose that would cause body
      temperature to decrease by 1 degree C. Both measures gave the progression of
      toxicity from least to most potent of methanol less than ethanol less than 2
      propanol less than 1-propanol less than 2-butanol less than 1-butanol. The
      effective dose of each alcohol was compared to its membrane/buffer partition
      coefficient (Pm/b), and there was a high inverse correlation between the
      hypothermic dose of an alcohol and its lipid solubility. That the potency of an
      alcohol was strongly correlated with its Pm/b suggests that the membrane
      disordering theory of narcosis may also be used to explain the hypothermic action
      of alcohols.

PMID- 1995925
TI  - Comparison of rats of the Fischer 344 and Long-Evans strains in their autonomic
      thermoregulatory response to trimethyltin administration.
AB  - The purpose of this study was to assess the effect of genetic strain on the acute
      and long-term thermoregulatory response to the neurotoxicant trimethyltin (TMT)
      in rats of the Long-Evans (LE) and Fischer 344 (FCH) strains. In one study basic
      thermoregulatory responses including colonic temperature (Tc), metabolic rate
      (MR), evaporative water loss (EWL), motor activity (MA), and thermal conductance
      (Cd) were measured in both rat strains at ambient temperatures (Ta) of 10, 28,
      and 37 degrees C. It was found that the LE rat has a significantly higher Tc when
      it is measured in their home cage. Because of its smaller body mass the FCH rat
      has a higher MR at all Ta values. The FCH rat also has a greater rate of EWL
      during exposure to a Ta of 37 degrees C. Following iv administration of 8.0 mg/kg
      TMT both rat strains become significantly hypothermic; however, the effect
      differed significantly between the strains. At 26-34 d after TMT exposure
      thermoregulatory responses at Ta values of 10-37 degrees C were generally similar
      to that of the saline controls. Overall, the LE and FCH strains of rat exhibit
      some distinct thermoregulatory differences in response to changes in Ta.

PMID- 1995926
TI  - Influence of ethanol on microsomal p-nitrophenol hydroxylation and
      ethoxyresorufin deethylation in rat liver and lung.
AB  - The ability of ethanol to induce the deethylation of ethoxyresorufin and
      hydroxylation of p-nitrophenol in rat lung and liver was investigated. The
      administration of 10% ethanol in the drinking water for 7 d increased hepatic p
      nitrophenol hydroxylation twofold whereas ethanol ip (3 ml/kg/d for 7 d)
      decreased the activity. Both ethanol treatments decreased the activity in the
      lung. Ethoxyresorufin deethylation was induced in the liver by both ethanol
      treatments, and in the lung the bolus dosing ip increased the activity four-fold.
      The results indicate that the lung microsomes have p-nitrophenol hydroxylase and
      ethoxyresorufin deethylase activities, but only the latter was increased by
      ethanol treatment.

PMID- 1995927
TI  - Assessment of the human health risks posed by exposure to chromium-contaminated
      soils.
AB  - Millions of tons of chromite-ore processing residue have been used as fill in
      various locations in northern New Jersey and elsewhere in the United States. The
      primary toxicants in the residue are trivalent chromium [Cr(III)] and hexavalent
      chromium [Cr(VI)]. The hazard posed by Cr(III) is negligible due to its low acute
      and chronic toxicity. In contrast, Cr(VI) is a human carcinogen following
      inhalation of high concentrations. It can also cause allergic contact dermatitis.
      This evaluation addresses a residential site where the arithmetic mean (x) and
      geometric mean (gm) concentrations of Cr(III) in soil were 2879 and 1212 mg/kg
      (ppm). The mean and geometric mean concentrations of Cr(VI) were 180 and 4 mg/kg,
      respectively. The uptake (absorbed dose) of Cr(III) via soil ingestion,
      consumption of homegrown vegetables, and ingestion of inspired particles was
      determined. The uptake of Cr(VI) via dermal absorption from contact with surface
      soil and building wall surfaces, as well as inhalation, was also evaluated. The
      techniques used in this assessment are applicable for evaluating the human health
      risks posed by any residential site having contaminated soil. The potential for
      both sensitized and unsensitized persons to develop allergic contact dermatitis
      due to exposure to soil contaminated at these levels was found to be negligible.
      The estimated average daily dose (ADD) via ingestion and dermal absorption for
      the maximally exposed individual (MEI) was about 1500- and 40-fold below the EPA
      reference dose (RfD) for Cr(III) and Cr(VI), respectively. It was shown that for
      residential sites, the most important route of exposure to Cr(III) was incidental
      soil ingestion. Although not relevant to these sites specifically, if garden
      vegetables could be successfully grown in these soils, then they would probably
      be the predominant source of uptake of Cr(III). Since inhalation of Cr(VI)
      contaminated dust (but not ingestion or dermal contact) poses a cancer hazard,
      the doses and associated risks were assessed. The estimated cancer risks for the
      MEI and most likely exposed individual (MLEI) were approximately 5 x 10(-9) and 2
      x 10(-9), respectively. These levels of risk have always been considered well
      below those that warrant regulatory concern. For persons living on residential
      properties, the cancer risk due to inhaling suspended particles is likely to be
      less than 1 in 1,000,000 if Cr(VI) levels in soil are less than 180 mg/kg (ppm).
      Based on this analysis, the levels of Cr(III) and Cr(VI) at this and similar
      sites do not pose a health hazard following acute or chronic exposure.

PMID- 1995928
TI  - Human exposures from dioxin in soil--a meeting report.
AB  - A 1984 risk assessment identified 1 part per billion (ppb) of dioxin in soil as a
      "level of concern" at Times Beach, Mo. The authors of the assessment had to rely
      on many assumptions in their analysis, but since that time, a number of
      investigators have obtained data that bear directly on estimating exposures from
      substances in soil. Partly because of the assumptions and partly because of the
      site-specific nature of their analysis, the authors of the Times Beach risk
      assessment cautioned against the adoption of 1 ppb as a delineator between
      acceptable and nonacceptable levels of contamination. Those cautions have been
      more frequently ignored than honored, and 1 ppb has become a de facto standard.
      In November 1989, the Center for Risk Management at Resources for the Future
      hosted 50 experts at a workshop that heard and discussed published and new
      research about exposure estimates and measures. The 1984 assessment identified
      soil ingestion by toddlers as the single most important source of exposure to
      dioxin in soil; it assumed that toddlers ingested 10 g soil daily. Research
      discussed at the workshop shows that the average child ingests about 0.04 g soil
      daily, but that 1 of 320 studied children ingested 5 g. These findings leave open
      the risk management decision about whether acceptable exposure levels should be
      established to protect the average child or the extreme child. Furthermore, the
      absence of children from commercial and industrial sites led to suggestions that
      higher concentrations of dioxin are acceptable in soil at such sites. Some
      workshop participants objected to those suggestions because of the difficulty of
      assuring that such sites would not revert to residential use in the future.
      Whether deed restrictions are sufficient to prevent such reversions was seen as
      an important research topic. Workshop participants repeatedly discussed the
      importance of site-specific data in estimating exposures: Measured half-lives of
      dioxin in different soils range from 18 mo to greater than 100 yr;
      bioavailability from various soils differs by at least 20-fold; and the amounts
      of soil ingested by grazing cattle can differ 20-fold depending on conditions.
      Workshop participants agreed upon some suggestions for research and generally
      favored the development of guidelines for exposure assessment that would allow
      consideration of site-specific information. Furthermore, they generally agreed
      that no single concentration should be taken as a level of concern. Instead,
      levels should be established that consider the planned uses of the sites.

PMID- 1995929
TI  - Practical field epidemiology to investigate a cholera outbreak in a Mozambican
      refugee camp in Malawi, 1988.
AB  - Of all populations affected by cholera, refugees are at particular risk of
      infection due to overcrowding and poor sanitation. Between 15 March and 17 May
      1988, 951 cases of cholera were registered at the cholera treatment centre in a
      Mozambican refugee camp in Malawi. The epidemic duration was 65 days. Vibrio
      cholerae biotype E1 Tor serotype Inaba was isolated. To identify high-risk groups
      and potential risk of acquiring the disease, an epidemiologic investigation was
      conducted. The attack rate of recorded cases was 2.6% with a range from 0.9 to
      5.1% for different sections of the camp. The case fatality rate was 3.3% and
      decreased from week 1 to week 6. The epidemic started in the section near the
      market place and radiated out. A matched-pair case-control study of food and
      water consumption was performed early in the outbreak. It showed that cases were
      more likely to use shallow wells (surface wells) instead of boreholes compared to
      controls (OR = 4.5, CI = 1.0-20.8, P = 0.04) and that cases were more likely to
      have had contact with the market than controls (OR = 3.5, CI = 0.7-16.8, P =
      0.09). None of the food items available at the market was more likely to be
      preferred by cases than controls. Recommendations included early case finding and
      treatment, temporary closure of the market, tetracycline prophylaxis of contacts,
      and water chlorination.

PMID- 1995930
TI  - Coincidence of malaria parasitaemia and abnormal chest X-ray findings in young
      Gambian children.
AB  - Weekly surveillance of Gambian children aged less than 5 years for both acute
      lower respiratory infections (ALRI) and clinical malaria showed a high rate of
      coincidence between abnormal chest X-ray findings and high levels of malaria
      parasitaemia. Generalized interstitial X-ray changes were particularly associated
      with these cases of malaria parasitaemia. It is suggested that such ALRIs in
      these children may be attributable to malaria.

PMID- 1995931
TI  - Skin sensitivity to capsulatum and duboisii histoplasmins in Nigeria.
AB  - A total of 1313 persons comprising 1087 healthy subjects and 226 hospital
      patients with bronchopulmonary disorders were tested for reactivity to
      histoplasmins prepared from Histoplasma capsulatum and H. capsulatum var.
      duboisii. The overall sensitivity rates to the two antigens were 3.5 and 3.0%
      respectively. The incidence of sensitivity in the hospital patients was
      significantly higher (8.85% for 'capsulatum' antigen and 6.64% for 'duboisii'
      antigen) than that in different categories of the healthy population (1.66-5.03%
      and 0.5-4.47%, respectively). The majority of persons who had a positive reaction
      to duboisii antigen also reacted positively to capsulatum antigen and vice versa.

PMID- 1995932
TI  - Unusual neuropsychiatric manifestations of enteric fever.
AB  - Enteric fever, a common problem in the tropics, may present with unusual
      neuropsychiatric complications. Three patients presenting as catatonic
      schizophrenia, encephalomyelitis and pseudo-bulbar palsy are reported. Early
      recognition and management of the cause of such presentations can reduce
      morbidity and mortality.

PMID- 1995933
TI  - Rouleaux formation in sickle cell traits.
AB  - Rouleaux formation of washed red blood cells (r.b.c.s) from subjects with sickle
      cell trait (HbAS) was measured by the rapid coagulation method. The r.b.c.s were
      suspended in the donor's native plasma or in 1.3% dextran in phosphate-buffered
      Ringer solution at pHs of 6.5, 7.4 and 8.2. HbAS cells showed more rouleaux
      formation than HbAA (normal) cells in plasma (P less than 0.005). Plasma
      fibrinogen concentration of HbAS and HbAA subjects did not differ significantly
      (mean 2.9, s.d. 0.7 g l-1 for both groups). In the dextran solution, HbAS cells
      were more aggregable at pH 6.5 but less at pH 8.2 than HbAA cells. There was no
      significant difference in dextran-induced aggregation between the two groups of
      cells at pH 7.4. The results suggest that HbAS subjects may be more prone to
      intravascular sludging and stasis and that this risk may be enhanced by reduction
      in pH of blood.

PMID- 1995934
TI  - Proguanil daily or chlorproguanil twice weekly are efficacious against falciparum
      malaria in a holoendemic area of Tanzania.
AB  - The prophylactic efficacy of proguanil 100 mg (Paludrine) daily was compared to
      that of chlorproguanil 20 mg (Lapudrine) twice weekly in school children from
      Nyamisathi village, in a coastal area of Tanzania, 160 km south of Dar es Salaam.
      A total of 80 children were randomly allocated to three groups after radical
      treatment with a curative dose of mefloquine (Lariam). Seventy-six children were
      then followed up with daily prophylaxis and/or placebo for 13 weeks. All children
      in the group taking placebo prophylaxis were reinfected within 10 weeks whereas
      no parasites were detected in the children taking proguanil or chlorproguanil for
      prophylaxis. We conclude that both regimens were efficacious and that
      chlorproguanil represents an important alternative for chemoprophylaxis if taken
      at least twice weekly instead of the recommended once weekly regimen.

PMID- 1995935
TI  - Campylobacter jejuni as a cause of acute diarrhoea in children: a study at an
      urban hospital in Bangladesh.
AB  - The importance of C. jejuni as an aetiological agent of childhood diarrhoea was
      investigated at an urban children's hospital in Dhaka over a period of 1 year. C.
      jejuni was isolated from 25.5% of 102 diarrhoeal patients compared to 8.6% of 93
      age and sex-matched healthy control children studied (P less than 0.002). The
      organism was isolated as a single pathogen in 17.6% of diarrhoeal patients. No C.
      coli was detected. The infection rate was significantly higher (P less than 0.05)
      amongst children up to 1 year of age (32.8%) compared to those aged over 1 year
      (15.9%). The clinical features of the majority of Campylobacter-positive cases
      resembled toxin-mediated secretory type diarrhoea. A fourfold rise of antibody
      titre against autologous Campylobacter strains was observed in the convalescent
      sera of Campylobacter-positive cases. The findings strongly suggest that C.
      jejuni is an important aetiological agent of childhood diarrhoea amongst Bengali
      children and therefore should be looked for in diarrhoeal illness.

PMID- 1995936
TI  - Thyroid abscess 'an unusual complication of typhoid fever'.

PMID- 1995937
TI  - Giardiasis and amoebiasis infections in three Saudi closed communities.
AB  - Two hundred and eighteen residents (131 healthy and 87 mentally or physically
      retarded) of a children's nursery, a foster house and a rehabilitation centre for
      the handicapped in Abha, southwestern Saudi Arabia, were examined for intestinal
      parasitism. About 30% of the population of the three communities were found to
      harbour asymptomatic infections with either Giardia lamblia and/or Entamoeba spp.
      Giardia cysts were identified in 19.3% of those examined. Entamoeba histolytica
      was found in 18.4% of the residents of the rehabilitation centre only. Entamoeba
      coli infections were found in residents of both the foster house and
      rehabilitation centre (6.0 and 25.3% respectively). The prevalence of infection
      with the three parasites was significantly higher in the rehabilitation centre
      than in the children's nursery and foster house.

PMID- 1995938
TI  - A comparison of local handwashing agents in Bangladesh.
AB  - The efficacy of handwashing using ash, soap, mud or plain water was tested in a
      group of 20 women living in a slum of Dhaka in Bangladesh. Each woman was asked
      to wash her hands using each of the washing agents and the efficacy of
      handwashing was assessed by comparing estimated faecal coliform counts from post
      washing hand samples. Mud and ash were found to be as efficient as soap. Research
      on appropriate handwashing techniques in the light of the existing practices is
      suggested.

PMID- 1995939
TI  - Clinical diagnosis of malaria: can we improve?
AB  - Most cases of malaria in Zimbabwe are diagnosed on the basis of clinical
      suspicion, without laboratory tests. Of patients treated, between 10 and 30% have
      malaria parasites on blood slide examination. Can diagnosis be improved by a
      systematic history? We examined this question in 287 patients treated for malaria
      in an area of year-round transmission in Zimbabwe. The most common complaints
      were 'headache' (85.7%), 'bodily weakness' (79.0%) and 'fever/feeling hot'
      (73.2%). Eighty patients (28%) had malaria parasites on blood smear. Using the
      blood slide as the standard, we calculated the sensitivity, specificity and
      positive predictive value of a variety of clinical symptoms and signs. None had a
      positive predictive value substantially higher than the unknown diagnostic
      criteria used by health workers (28%). Multivariate analysis showed that 15
      different demographic and clinical variables did not significantly predict a
      positive blood slide result. We conclude that, in this setting, clinical history
      alone will not improve the diagnosis of malaria.

PMID- 1995940
TI  - Development of a protocol for early treatment of endemic meningitis in children
      in Vanuatu.
AB  - Meningitis is endemic in Vanuatu and other Pacific island countries and has a
      high case fatality rate. The incidence in the southern island of Tanna is
      especially high. This descriptive study of 64 cases in children (under 15 years)
      on that island was undertaken over a 21-month period from January 1988 to
      September 1989. Meningococcus was identified in 23 cases (36%) and Pneumococcus
      in 12 (19%). The age distribution showed a high rate in under 1 year olds. The
      symptoms of fever, convulsion and vomiting were most common. Bulging fontanelle
      (in children under 1 year), neck rigidity, and altered level of consciousness
      were the most frequent signs. These signs were as frequent in meningococcal as
      pneumococcal infections and were used to develop a simple protocol for use in
      primary care. Delay in treatment or referral because of patients seeking
      traditional medicine is a major problem yet to be overcome. Only a weak
      association between admissions with meningitis and underweight or crowding was
      found in this study.

PMID- 1995941
TI  - Human immunodeficiency virus as a prototypic complex retrovirus.

PMID- 1995942
TI  - Direct measurement of soluble CD4 binding to human immunodeficiency virus type 1
      virions: gp120 dissociation and its implications for virus-cell binding and
      fusion reactions and their neutralization by soluble CD4.
AB  - We have analyzed the binding of soluble CD4 (sCD4) to human immunodeficiency
      virus type 1 (HIV-1) virions (isolates IIIB and RF) at 4 and 37 degrees C by
      using a combination of gel exclusion chromatography and enzyme-linked
      immunosorbent assay detection systems. The sCD4 binding curve at 37 degrees C
      indicates that the affinity of the interaction of sCD4 with gp120 on the virion
      surface is indistinguishable from the affinity of sCD4 for the equivalent
      concentration of soluble gp120. At 4 degrees C, however, the affinity of sCD4 for
      virion-bound gp120 but not for soluble gp120 is reduced by about 20-fold. Binding
      of sCD4 (greater than 0.2 microgram/ml) to virions at 37 degrees C but not 4
      degrees C induces the rapid dissociation of a major proportion of gp120 from gp41
      on the virion surface. This dissociation requires occupancy by sCD4 of multiple
      (probably two) binding sites on a gp120-gp41 oligomer. At 37 degrees C there are
      two components to the neutralizing action of sCD4 on HIV-1; reversible,
      competitive inhibition at low sCD4 concentrations (less than 0.2 microgram/ml)
      and essentially irreversible inhibition due to gp120 loss at higher sCD4
      concentrations. At 4 degrees C, sCD4 neutralizes HIV infectivity by competitive
      inhibition alone. These findings may have implications for the HIV-CD4+ cell
      binding and fusion reactions and the mechanism by which sCD4 blocks infectivity.

PMID- 1995943
TI  - Sequential rearrangement and nuclear polymerization of actin in baculovirus
      infected Spodoptera frugiperda cells.
AB  - Proper assembly of nucleocapsids of the baculovirus Autographa californica
      nuclear polyhedrosis virus is prevented by cytochalasin D, a drug that interferes
      with actin microfilament function. To investigate the involvement of
      microfilaments in A. californica nuclear polyhedrosis virus replication, a
      fluorescence microscopy study was conducted that correlated changes in
      distribution of microfilaments with events in the life cycle of the virus.
      Tetramethylrhodamine isothiocyanate-labeled phalloidin was used to label
      microfilaments, and monoclonal antibody was used to label p39, the major viral
      capsid protein. Three microfilament arrangements were found in infected cells.
      During uptake of virus, thick cables were formed. These were insensitive to
      cycloheximide, indicating that this configuration was a rearrangement of
      preexisting cellular actin mediated by a component of the viral inoculum. At the
      time of cell rounding and before viral DNA replication, ventral aggregates of
      actin were observed. These were sensitive to cycloheximide but not to
      aphidicolin, indicating that an early viral gene mediated this actin
      rearrangement. Ventral aggregates did not result from the rounding process
      itself. Uninfected cells prerounded with colchicine did not form ventral
      aggregates. Cells prerounded with colchicine and then infected did form
      aggregates. At the time of exponential production of progency virus,
      microfilaments were found in the nucleus surrounding the virogenic stroma. In
      this area (where nucleocapsid assembly is known to take place) microfilaments
      colocalized with p39. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      and Western immunoblot analysis identified p39 among proteins retained on an f
      actin affinity column. We postulate that microfilaments in the nucleus provide a
      scaffold to position capsids for proper assembly and filling with DNA.

PMID- 1995944
TI  - Induction of human immunodeficiency virus type 1 expression in chronically
      infected cells is associated primarily with a shift in RNA splicing patterns.
AB  - We have analyzed the kinetics of human immunodeficiency virus type 1 (HIV-1) RNA
      induction in chronically infected T cells and promonocytes. A substantial amount
      of spliced mRNAs and assembled virions was found in resting cells. Induction
      increased the steady-state level of total HIV-1 RNA by 4-fold but increased the
      level of unspliced transcripts by 25-fold. This increase in unspliced RNA was
      reflected in the amount of virus seen by electron microscopy. These data suggest
      a mechanism for the induction of HIV-1 RNA in chronically infected cells
      involving a shift in splicing greatly favoring the stability of unspliced viral
      RNA with only a modest increase in total viral RNA. Analysis of the relative
      abundance of transcript classes is critical to the measurement of HIV-1 viral
      replication kinetics.

PMID- 1995945
TI  - Morphogenetic and regulatory effects of mutations in the envelope proteins of an
      avian hepadnavirus.
AB  - The envelope gene of the avian hepadnavirus, duck hepatitis B virus, was mutated
      in order to dissect the functions of the two major envelope proteins pre-S/S and
      S. Both envelope proteins were found to be required for virus particle assembly
      and secretion. The placement of stop codons after each of the first three AUG
      codons in the pre-S region allowed efficient translational initiation at
      downstream AUG codons to produce novel N-terminally truncated pre-S/S proteins.
      These proteins could substitute for pre-S/S protein in the production of
      enveloped virus production, but not in the production infectious virus. A mutant
      defective in myristylation of the pre-S/S protein produced reduced amounts of
      enveloped virus, and this virus was not infectious. Mutants defective in the pre
      S/S protein accumulated high levels of covalently closed circular viral DNA
      (cccDNA) compared with the wild type or with a mutant defective in only the S
      protein. Hyperamplification of cccDNA resulted in high levels of viral RNA,
      consistent with the proposed role of cccDNA as the transcriptional template.
      Myristylation of the pre-S/S protein was not required for control of cccDNA
      amplification, and mutants that produced N-terminally truncated pre-S/S proteins
      displayed higher levels of cccDNA. We concluded that the pre-S/S protein, but not
      the S protein, is required for control of cccDNA amplification and persistent
      infection.

PMID- 1995946
TI  - A specific inhibitor of cysteine proteases impairs a Vif-dependent modification
      of human immunodeficiency virus type 1 Env protein.
AB  - The Vif protein of human immunodeficiency virus type 1 (HIV-1) regulates viral
      infectivity. Virions produced in cell culture after transfection by a Vif
      negative molecular clone show a dramatic decrease in infectivity for susceptible
      CD4+ cell lines, although the Vif protein does not appear to be a constituent of
      the viral particle. The exact mechanism by which Vif affects HIV-1 infectivity is
      so far unknown. We report the existence of structural homologies between Vif and
      a family of cysteine proteases and present evidence which suggests that one of
      the targets of Vif is the Env protein and more precisely the cytoplasmic domain
      of gp41. Vif was found to modify both the processing and conformation of the Env
      protein. Ethyl(25, 35)- 3[(5)-3-methyl-1-(3-methylbutylcarbamoyl)]oxirane-2
      carboxylate, a specific inhibitor of cysteine proteases, inhibits the effect of
      Vif, as does the mutation of Cys-114 to Leu in Vif. Furthermore, Cys-114 of Vif
      produced in Escherichia coli, interacts directly with trans-epoxysuccinyl-L
      leucylamido-(4-guanidino)butane. These observations suggest that a cysteine
      protease activity is associated with Vif and that this activity plays a role in
      Env maturation.

PMID- 1995947
TI  - Defective transport of Sindbis virus glycoproteins in End4 mutant Chinese hamster
      ovary cells.
AB  - Mutant V.24.1, a temperature-sensitive derivative of Chinese hamster ovary cells,
      defines the End4 complementation group of mutants selected for resistance to
      protein toxins and has defective lysosomes at the restrictive temperature (P. A.
      Colbaugh, M. Stookey, and R. K. Draper, J. Cell Biol. 108:2211-2219, 1989). We
      have investigated the biosynthesis of Sindbis virus envelope glycoproteins in
      V.24.1 cells. When the cells were infected at the restrictive temperature, the
      envelope glycoproteins E1 and E2 were undetectable on the cell surface and
      proteolytic processing of the precursor protein pE2 to envelope protein E2 did
      not occur. Protein retained intracellularly was sensitive to endoglycosidase H
      and, by immunofluorescence localization, appeared to accumulate in the
      endoplasmic reticulum. We conclude that the genetic defect in V.24.1 cells
      impairs the transport of Sindbis virus glycoproteins, apparently at the level of
      export from the endoplasmic reticulum.

PMID- 1995948
TI  - Two spatially distinct genetic elements constitute a bipartite DNA replication
      origin in the minute virus of mice genome.
AB  - Mutations were introduced into plasmid pMM984, a full-length infectious clone of
      the fibrotropic strain of minute virus of mice, to identify cis-acting genetic
      elements required for the excision and replication of the viral genome. The
      replicative capacity of these mutants was measured directly, using an in vivo
      transient DNA replication assay following transfection of plasmids into murine A9
      cells and primate COS-7 cells. Experiments with subgenomic constructs indicated
      that both viral termini must be present on the same DNA molecule for replication
      to occur and that the viral nonstructural protein NS-1 must be provided in trans.
      The necessary sequences were located within 1,084 and 807 nucleotides of the 3'
      and 5' ends of the minute virus of mice genome, respectively. The inhibitory
      effect of deletions within the 206-bp 5'-terminal palindrome demonstrated that
      these sequences comprise a cis-acting genetic element that is absolutely
      essential for the excision and replication of viral DNA. The results further
      indicated a requirement for a stem-plus-arms T structure as well as for the
      formation of a simple hairpin. In addition, the removal of one copy of a tandemly
      arranged 65-bp repeat found 94 nucleotides inboard of the 5'-terminal palindrome
      inhibited viral DNA replication in cis by 10- and just greater than 100-fold in
      A9 and COS-7 cells, respectively. The latter results define a novel genetic
      element within the 65-bp repeated sequence, distinct from the terminal
      palindrome, that is capable of regulating minute virus of mice DNA replication in
      a species-specific manner.

PMID- 1995949
TI  - Cellular factors regulate transactivation of human immunodeficiency virus type 1.
AB  - It is hypothesized that the immediate-early (IE) gene products of human
      cytomegalovirus (CMV) and the transactivator (TAT) of human immunodeficiency
      virus type 1 (HIV-1) regulate HIV-1 gene expression through mechanisms involving
      host cell factors. By using transient transfection assays with the gene for
      chloramphenicol acetyltransferase (CAT) under the transcriptional control of the
      HIV-1 long terminal repeat (LTR), we examined transactivation of the LTR by
      plasmids that express either the HIV-1 gene for TAT or human CMV IE. The ratio of
      the level of transactivation by CMV IE to the level of transactivation by TAT
      varied up to 1,000-fold between cell types. The difference in the activities of
      these transactivators in various cell types was not a consequence of differential
      expression of the transactivator gene. Analysis of RNA species initiated in the
      HIV-1 LTR supports the conclusion that cellular factors regulate the level of
      elongation of the transcription complex on the LTR. Furthermore, evidence that in
      some cell types the predominant mechanism of transactivation by HIV-1 TAT
      involves posttranscriptional processes is presented.

PMID- 1995950
TI  - Carboxy-terminally truncated dengue virus envelope glycoproteins expressed on the
      cell surface and secreted extracellularly exhibit increased immunogenicity in
      mice.
AB  - Recombinant vaccinia viruses expressing C-terminally truncated E's that ranged in
      length from 9 to 99% of the N-terminal sequence were constructed. The overall
      antigenicity of the E products was analyzed by radioimmunoprecipitation, using
      dengue virus hyperimmune mouse ascitic fluid (HMAF) or an anti-E peptide serum.
      Truncated E that was 79% or less in length did not bind HMAF efficiently, whereas
      E constructs greater than 79% were able to bind HMAF with high efficiency. The
      first 392 amino acids of the dengue type 4 virus E sequence, including the Arg
      392 following the 79% E C terminus, appeared to be critical for proper antigenic
      structure required for efficient binding by HMAF. Truncated E's ranging from 59
      to 81% in length were secreted extracellularly, whereas smaller or larger E's
      were retained intracellularly. Secreted E's contained carbohydrate side chains
      that were resistant to endoglycosidase H digestion, suggesting that the transport
      of E occurs via a pathway from the rough endoplasmic reticulum through the Golgi
      complex. 79% E-RKG (which possessed the three additional amino acids immediately
      downstream of 79% E) was expressed at a high concentration on the surface of
      recombinant virus-infected cells presumably being inserted into the plasma
      membrane by a hydrophobic C-terminal membrane anchor. Evaluation in mice of the
      protective efficacy of the various vaccinia virus E recombinants indicated that
      only truncated E's that were recognized efficiently by HMAF induced a high level
      of resistance to dengue virus encephalitis. 79% E-RKG which is expressed at a
      high concentration on the surface of infected cells was highly immunogenic when
      tested for induction of an E antibody response. This suggests that cell surface
      expression of 79% E-RKG was responsible for its enhanced immunogenicity. Finally,
      passive immunization studies indicated that serum antibodies to E played a major
      role in the complete or nearly complete resistance to dengue virus challenge
      induced by certain vaccinia virus-truncated E recombinants.

PMID- 1995951
TI  - Variable role of the long terminal repeat Sp1-binding sites in human
      immunodeficiency virus replication in T lymphocytes.
AB  - The long terminal repeat (LTR) of the human immunodeficiency virus (HIV) contains
      three binding sites for the transcriptional factor Sp1. In order to investigate
      the role that the Sp1-binding sites play in regulation of HIV replication, we
      have introduced a deletion of all three Sp1-binding sites into the LTR of an
      infectious molecular clone of HIV. Viral stocks have been prepared from this
      mutant virus, designated dl-Sp, and these stocks have been used to study its
      replicative ability in human T cells. The dl-Sp virus replicated efficiently in
      MT4 cells and in phytohemagglutinin-stimulated human peripheral blood
      lymphocytes, but it replicated poorly and with delayed kinetics in A3.01 (CEM) T
      cells unless those cells had been treated with the cytokine tumor necrosis factor
      alpha. Gel retardation assays to study the levels of DNA-binding proteins present
      in these cells showed that NF-kappa B activity could be detected in the nuclei of
      MT4 cells but not in A3.01 cells unless they had been treated with tumor necrosis
      factor alpha. Thus, the presence of NF-kappa B activity appeared to be required
      for efficient replication of an HIV whose LTR Sp1-binding sites had been deleted.
      This suggests that NF-kappa B can functionally compensate for Sp1 in activating
      HIV replication. The HIV LTR is therefore similar to the promoter-enhancer units
      of other viruses in that it is composed of multiple functional elements that may
      contribute differently to viral replication depending on the levels of DNA
      binding proteins present in the target cells.

PMID- 1995952
TI  - Dextran sulfate blocks antibody binding to the principal neutralizing domain of
      human immunodeficiency virus type 1 without interfering with gp120-CD4
      interactions.
AB  - The mechanism of the antiviral activity of sulfated polysaccharides on human
      immunodeficiency virus type 1 (HIV-1) was investigated by determining the effect
      of dextran sulfate on the binding of CD4 and several anti-gp120 monoclonal
      antibodies to both recombinant and cell surface gp120. Dextran sulfate did not
      interfere with the binding of sCD4 to rgp120 on enzyme-linked immunosorbent assay
      (ELISA) plates or in solution and did not block sCD4 binding to HIV-1-infected
      cells expressing gp120 on the cell surface. Dextran sulfate had minimal effects
      on rgp120 binding to CD4+ cells at concentrations which effectively prevent HIV
      replication. In contrast, it potently inhibited the binding of both rgp120 and
      cell surface gp120 to several monoclonal antibodies directed against the
      principal neutralizing domain of gp120 (V3). In an ELISA format, dextran sulfate
      enhanced the binding of monoclonal antibodies against amino-terminal regions of
      gp120 and had no effect on antibodies directed to other regions of gp120,
      including the carboxy terminus. The inhibitory effects of polyanionic
      polysaccharides on viral binding, viral replication, and formation of syncytia
      therefore appear mediated by interactions with positively charged amino acids
      concentrated in the V3 region. This high local positive charge density, unique to
      the V3 loop, leads us to propose that this property is critical to the function
      of the V3 region in mediating envelope binding and subsequent fusion between
      viral and cell membranes. The specific interaction of dextran sulfate with this
      domain suggests that structurally related molecules on the cell surface, such as
      heparan sulfate, may be additional targets for HIV binding and infection.

PMID- 1995953
TI  - Mechanism of altered Sindbis virus neurovirulence associated with a single-amino
      acid change in the E2 Glycoprotein.
AB  - The mechanism by which amino acid changes in the E1 and E2 surface glycoproteins
      of Sindbis virus affect neurovirulence is unknown. We have studied two
      recombinant viruses which differ in virulence. One (TE) contains Gly and the
      other (TES) contains Arg at position 172 in E2. TE causes more rapid death than
      TES in newborn mice. Both viruses replicate similarly in nonneuronal cells, but
      TE replicates more rapidly in the brains of newborn mice and in neuroblastoma
      cells. TE also induces earlier viral RNA synthesis in neuroblastoma cells. 35S
      labeled TE binds more efficiently to brain and neuroblastoma cells, but not to
      nonneuronal cells, than TES. We propose that a region of the E2 glycoprotein
      affected by the amino acid occupying position 172 is important for binding to an
      alphavirus receptor on neurons and influences neurovirulence by this mechanism.

PMID- 1995954
TI  - Deletion analysis of the 5' untranslated leader sequence of tobacco mosaic virus
      RNA.
AB  - To determine the sequences essential for viral multiplication in the 5'
      untranslated leader sequence of tobacco mosaic virus RNA, mutant TMV-L (a tomato
      strain) RNAs which carry several deletions in this 71-nucleotide sequence were
      constructed by an in vitro transcription system and their multiplication was
      analyzed by introducing mutant RNA into tobacco protoplasts by electroporation.
      Large deletions of the sequence from nucleotides 9 to 47 or 25 to 71 abolished
      viral multiplication; when about 10-nucleotide deletions were introduced
      throughout this 5' leader sequence, only deletion of the sequence from
      nucleotides 2 to 8 abolished detectable viral multiplication. This mutant RNA,
      however, directed the synthesis of the 130,000-molecular-weight protein in a
      rabbit reticulocyte lysate in vitro translation system, and consequently this 5'
      proximal portion appears likely to be essential for replication.

PMID- 1995955
TI  - Human T-cell leukemia-lymphoma virus type I (HTLV-I) expression in fresh
      peripheral blood mononuclear cells from patients with tropical spastic
      paraparesis/HTLV-I-associated myelopathy.
AB  - Tropical spastic paraparesis/human T-cell leukemia-lymphoma virus type I (HTLV-I)
      associated myelopathy (TSP/HAM) is a chronic neurological illness
      epidemiologically associated with HTLV-I infection. We investigated the role of
      HTLV-I in the pathogenesis of this disease by studying viral expression in fresh
      uncultured peripheral blood mononuclear cells (PBMCs) of six patients of
      Caribbean origin with TSP/HAM. The PBMC genomic DNA of all the patients studied
      carried HTLV-I provirus, but viral expression was not detected by Northern (RNA)
      blot analysis of total cellular PBMC RNA. When the reverse transcriptase
      polymerase chain reaction technique was used with primers specific for the tax
      rex mRNA, all of the samples were positive for this viral mRNA species,
      regardless of the duration of the illness (range, 2 to 13 years). The splice
      junctions for the tax-rex mRNA described in cases of HTLV-I-induced adult T-cell
      leukemia (position 5183 of the envelope and position 7302 of the pX region) were
      identical in three TSP/HAM cases studied. To ascertain whether viral expression
      occurred at a low level in many cells or at a high level in a few permissive
      cells, we performed in situ hybridization on fresh PBMCs from two patients (2 and
      7 years after clinical diagnosis), seeking HTLV-I RNA sequences. Our finding
      indicated that in vivo HTLV-I expression occurred at a high level in a few cells
      (1 of every 5,000 PBMCs) in both cases studied. The fact that cells of all six
      patients with TSP/HAM were positive for viral expression, regardless of the time
      lag from diagnosis, suggests that persistent expression of a viral product(s) may
      be pivotal in the pathogenesis of TSP/HAM.

PMID- 1995957
TI  - Increased human immunodeficiency virus (HIV) expression in chronically infected
      U937 cells upon in vitro differentiation by hydroxyvitamin D3: roles of
      interferon and tumor necrosis factor in regulation of HIV production.

PMID- 1995956
TI  - Respiratory syncytial virus (RSV) F, G, M2 (22K), and N proteins each induce
      resistance to RSV challenge, but resistance induced by M2 and N proteins is
      relatively short-lived.
AB  - The ability of recombinant vaccinia viruses that separately encoded 9 of the 10
      known respiratory syncytial virus (RSV) proteins to induce resistance to RSV
      challenge was studied in BALB/c mice. Resistance was examined at two intervals
      following vaccination to examine early (day 9) as well as late (day 28) immunity.
      BALB/c mice were inoculated simultaneously by the intranasal and intraperitoneal
      routes with a recombinant vaccinia virus encoding one of the following RSV
      proteins: F, G, N, P, SH, M, 1B, 1C, or M2 (22K). A parainfluenza virus type 3 HN
      protein recombinant (Vac-HN) served as a negative control. One half of the mice
      were challenged with RSV intranasally on day 9, and the remaining animals were
      challenged on day 28 postvaccination. Mice previously immunized by infection with
      RSV, Vac-F, or Vac-G were completely or almost completely resistant to RSV
      challenge on both days. In contrast, immunization with Vac-HN, -P, -SH, -M, -1B,
      or -1C did not induce detectable resistance to RSV challenge. Mice previously
      infected with Vac-M2 or Vac-N exhibited significant but not complete resistance
      on day 9. However, in both cases resistance had largely waned by day 28 and was
      detectable only in mice immunized with Vac-M2. These results demonstrate that F
      and G proteins expressed by recombinant vaccinia viruses are the most effective
      RSV protective antigens. This study also suggests that RSV vaccines need only
      contain the F and G glycoproteins, because the immunity conferred by the other
      proteins is less effective and appears to wane rapidly with time.

PMID- 1995958
TI  - Desert Storm--moves into history.

PMID- 1995959
TI  - Too few human organs for transplantation, too many in need . . . and the gap
      widens.

PMID- 1995960
TI  - Physicians' attitudes and approaches are pivotal in procuring organs for
      transplantation.

PMID- 1995961
TI  - From the Food and Drug Administration.

PMID- 1995962
TI  - From the Centers for Disease Control. Mosquito-transmitted malaria--California
      and Florida, 1990.

PMID- 1995963
TI  - From the Centers for Disease Control. Cholera--Peru, 1991.

PMID- 1995964
TI  - A piece of my mind. No laughing matter.

PMID- 1995965
TI  - Comorbidity of mental disorders and nicotine dependence.

PMID- 1995966
TI  - Smoking affects nocturnal blood pressure.

PMID- 1995967
TI  - Reducing tobacco consumption in California: Proposition 99 seems to work.

PMID- 1995968
TI  - A national health insurance tax on tobacco and alcohol: the puritan HIT.

PMID- 1995969
TI  - Tobacco coupons and teenagers.

PMID- 1995970
TI  - Psychiatric problems in obese children followed up for 10 years.

PMID- 1995971
TI  - Potentiation of warfarin anticoagulation by acetaminophen.

PMID- 1995972
TI  - Prevention and Management of hiv-contaminated needlesticks.

PMID- 1995973
TI  - Medicare Peer Review Organization preprocedure review criteria. An analysis of
      criteria for three procedures.
AB  - The Medicare Peer Review Organization (PRO) program includes preprocedure review
      using explicit criteria to assess the appropriateness of specific procedures.
      This study evaluates the variability in the PRO preprocedure criteria for the
      three procedures most frequently reviewed by PROs: carotid endarterectomy,
      cataract removal, and cardiac pacemaker implants. In August 1989, the PRO review
      criteria were received from the Health Care Financing Administration. To provide
      a reference point for reviewing the PRO criteria, national practice guidelines
      for these three procedures were identified. Wide variability was demonstrated in
      the PRO procedure-specific carotid endarterectomy and cataract removal review
      criteria among PROs, and the criteria differed significantly from the identified
      practice guidelines. The criteria for cardiac pacemaker implants were somewhat
      less variable, and were based, to varying degrees, on practice guidelines
      developed by the American College of Cardiology (ACC). Greater attention is
      needed to improve the development of review criteria, including the use of
      relevant practice guidelines, to ensure that review criteria are optimal.

PMID- 1995974
TI  - Neurobehavioral effects of phenytoin prophylaxis of posttraumatic seizures.
AB  - In order to determine potential negative neurobehavioral effects of phenytoin
      given to prevent the development of posttraumatic seizures, 244 subjects were
      randomized to phenytoin or placebo. They received neurobehavioral assessments at
      1 and 12 months postinjury while receiving their assigned drug and at 24 months
      while receiving no drugs. In the severely injured, phenytoin significantly
      impaired performance at 1 month. No significant differences were found as a
      function of phenytoin in the moderately injured patients at 1 month or in either
      severity group at 1 year. Patients who stopped receiving phenytoin according to
      protocol between 1 and 2 years improved more than corresponding placebo cases on
      several measures. We conclude that phenytoin has negative cognitive effects.
      This, combined with lack of evidence for its effectiveness in preventing
      posttraumatic seizures beyond the first week, raises questions regarding its use
      for long-term prophylaxis. Our findings do not negate phenytoin's proven efficacy
      in controlling established seizures nor do they indicate that its cognitive
      effects are worse than other anticonvulsant drugs.

PMID- 1995975
TI  - Physical and pharmacologic restraint of nursing home patients with dementia.
      Impact of specialized units.
AB  - This case-control study of 31 specialized dementia units and 32 traditional units
      in five states investigated use of physical and pharmacologic restraints among
      625 patients with the diagnosis of dementia. Physical restraints were observed in
      use on 18.1% of dementia unit patients and on 51.6% of comparison unit patients
      who were out of bed during the day (adjusted odds ratio, 0.283;95% confidence
      interval, 0.129 to 0.619). Pharmacologic restraints were routinely given to 45.3%
      of dementia unit patients and 43.4% of comparison unit patients (adjusted odds
      ratio, 0.950; 95% confidence interval, 0.611 to 1.477). We used multivariate
      logistic regression to identify residence in a nonspecialized nursing home unit,
      nonambulatory status, transfer dependency, mental status impairment, hip fracture
      history, and a high nursing staff-to-patient ratio, which we found to be
      independent predictors of physical restraint use. Physically abusive behavior,
      severe mental status impairment, and frequent family visitation were found to be
      significant predictors of pharmacologic restraint use, while advanced patient
      age, large nursing home size, and patient nonambulatory status were protective
      against such use. These results support the conclusion that physical and
      pharmacologic restraint constitute separate treatment modalities with different
      risk factors for use, and indicate that specialized dementia units are successful
      in reducing the use of physical but not pharmacologic restraints.

PMID- 1995976
TI  - Rising incidence of adenocarcinoma of the esophagus and gastric cardia.
AB  - Analyses of cancer incidence data from nine areas of the United States revealed
      steadily rising rates from 1976 to 1987 of adenocarcinomas of the esophagus and
      gastric cardia. The increases among men in this period ranged from 4% to 10% per
      year, and thus exceeded those of any other type of cancer. In contrast, there
      were relatively stable trends for squamous cell carcinoma of the esophagus and
      slight declines for adenocarcinoma of more distal portions of the stomach.
      Adenocarcinomas of the esophagus and gastric cardia disproportionately affected
      white men and rarely occurred among women. By the mid-1980s, among white men,
      adenocarcinomas accounted for about one third of all esophageal cancers, while
      cardia cancers accounted for about one half of all stomach cancers with specified
      subsites. The rising incidence rates and similar demographic patterns point to
      the need for investigation into the causes of these poorly understood cancers.

PMID- 1995977
TI  - Should alcoholics compete equally for liver transplantation?
AB  - The circumstances of liver transplantation are unique among organ transplantation
      because of the dire, absolute scarcity of donor livers and the predominance of
      one disease--alcohol-related end-stage liver disease--as the principal cause of
      liver failure. We propose that patients who develop end-stage liver disease
      through no fault of their own should have higher priority for receiving a liver
      transplant than those whose end-stage liver disease results from failure to
      obtain treatment for alcoholism. We base our proposal on considerations of
      fairness and on whether public support for liver transplantation can be
      maintained if, as a result of a first-come, first-served approach, patients with
      alcohol-related end-stage liver disease receive more than half the available
      donor livers. We conclude that since not all can live, priorities must be
      established for the use of scarce health care resources.

PMID- 1995978
TI  - Alcoholics and liver transplantation. The Ethics and Social Impact Committee of
      the Transplant and Health Policy Center.
AB  - Two arguments underlie a widespread unwillingness to consider patients with
      alcoholic cirrhosis of the liver as candidates for transplantation. First,
      alcoholics are morally blameworthy, their condition the result of their own
      misconduct; such blameworthiness disqualifies alcoholics in unavoidable
      competition for organs with others who are equally sick but blameless. Second,
      because of their habits, alcoholics will not exhibit satisfactory rates of
      survival after transplantation; good stewardship of a scarce lifesaving resource
      therefore requires that alcoholics not be considered for liver transplantation.
      These arguments are carefully analyzed and shown to be defective. There is not
      good moral or medical reason for categorically precluding alcoholics as
      candidates for liver transplantation. It would, in addition, be unjust to
      implement such a preclusion simply because others might respond negatively if we
      do not.

PMID- 1995979
TI  - Life or death. The issue of payment in cadaveric organ donation.

PMID- 1995980
TI  - Families' self-interest and the cadaver's organs. What price consent?

PMID- 1995981
TI  - Unwanted variations in the rules of practice.

PMID- 1995982
TI  - Neurobehavioral effects of anticonvulsants.

PMID- 1995983
TI  - AIDS warrior Joyce Wallace hopes to shelter homeless hookers.

PMID- 1995984
TI  - Desert Storm moves into eighth week.

PMID- 1995985
TI  - US (officially) honors physicians with first 'National Doctors' Day'.

PMID- 1995986
TI  - Childhood cancers gradually yielding to advances in diagnosis, therapy, knowledge
      of origin.

PMID- 1995987
TI  - From the National Institutes of Health.

PMID- 1995988
TI  - From the Centers for Disease Control. Increase in rubella and congenital rubella.

PMID- 1995989
TI  - From the Centers for Disease Control. Quarterly acquired immunodeficiency
      syndrome map.

PMID- 1995990
TI  - Intravascular erythrophagocytosis.

PMID- 1995991
TI  - A piece of my mind. Coming home.

PMID- 1995993
TI  - The Creation of Adam: divine funster decrees we are what we eat: chicken?

PMID- 1995992
TI  - Intrapleural tetracycline for recurrent pneumothorax.

PMID- 1995994
TI  - Are state mortality differences due to migration from the Rust Belt?

PMID- 1995995
TI  - Alternative immune globulin preparation when standard immune serum globulin is
      not available.

PMID- 1995996
TI  - Potential complications of high-dose epinephrine therapy in patients resuscitated
      from cardiac arrest.
AB  - Adults resuscitated from nontraumatic cardiac arrest who received intravenous
      epinephrine in doses chosen by the treating physician and who survived at least 6
      hours were studied to determine if high-dose epinephrine produced more
      complications than standard-dose. A total of 68 patients were enrolled and
      evaluated for postresuscitation complications attributable to epinephrine, using
      a two-tailed t test, and contingency analysis. The 33 patients receiving high
      dose epinephrine and 35 patients receiving standard-dose epinephrine were similar
      in demographics and variables known to affect outcome. There was no difference in
      potential complications between groups except serum calcium, which was 1.97
      mmol/L (SD, 0.20) in the high-dose epinephrine group and 2.10 (SD, 0.20) in the
      standard-dose group. Hospital discharge rates (18% in the high-dose vs 30% in the
      standard-dose group) and neurological status on discharge were not significantly
      different. High-dose epinephrine did not produce increased direct complications
      in this cardiac arrest population compared with standard-dose epinephrine.

PMID- 1995997
TI  - Are universal precautions effective in reducing the number of occupational
      exposures among health care workers? A prospective study of physicians on a
      medical service.
AB  - Using a daily questionnaire, we prospectively studied 277 physicians from two
      hospital medical services for incidents of exposure to blood and body fluids and
      barrier use before and after the implementation of universal precautions. We
      found that implementation significantly increased the frequency of barrier use
      during exposure incidents from 54% before implementation to 73% after
      implementation of universal precautions. Implementation led to a decrease in the
      number of exposure incidents that resulted in direct contact with blood and body
      fluids (actual exposures), from 5.07 to 2.66 exposures per physician per patient
      care month, and to an increase in averted exposures in which direct contact was
      prevented by the use of barrier devices, from 3.41 exposures per patient care
      month before implementation to 5.90 exposures per patient care month after
      implementation. Implementation affected neither the types of body fluid or
      procedures involved nor the overall rate of exposure incidents (8.5 per patient
      care month) but, through an increase in barrier use, it did prevent direct
      contact with blood and body fluids and thus converted what would have been an
      actual exposure into an averted one. We conclude that universal precautions were
      effective in reducing the risk of occupational exposures among physicians on a
      medical service.

PMID- 1995998
TI  - Prevalence of antibody to HIV-1 among entrants to US correctional facilities.
AB  - Prevalence of antibody to the human immunodeficiency virus type 1 (HIV-1) was
      assessed among 10,994 consecutive male and female entrants to 10 correctional
      systems in the United States. The HIV-1 seroprevalence for the 10 systems ranged
      from 2.1% to 7.6% for men and 2.5% to 14.7% for women; seroprevalence among women
      was higher than among men across nine of 10 systems. Using age 25 years to divide
      the population, HIV-1 prevalence among young women (5.2%) was significantly
      higher than among young men (2.3%), but similar to that in both older women
      (5.3%) and older men (5.6%). Overall, HIV-1 rates for nonwhites (4.8%) were
      higher than those for whites (2.5%). Although categories were identified across
      correctional systems, which may serve to focus prevention programs, variability
      in rates among correctional systems indicates that program planning must take
      local conditions into consideration.

PMID- 1995999
TI  - The clinical course of osteoporosis in anorexia nervosa. A longitudinal study of
      cortical bone mass.
AB  - Women with anorexia nervosa have reduced bone mass and may develop fractures.
      Neither the pathophysiology of this osteoporosis nor its natural history is
      known. To study the clinical course of osteoporosis, we followed up 27 women with
      anorexia nervosa for a median of 25 months (range, 9 to 53 months). At study
      entry, cortical bone density, measured by single-photon absorptiometry of the
      radial shaft, was low (mean +/- SD, 0.63 +/- 0.07 g/cm2) and inversely related to
      the duration of amenorrhea (r = -0.49). During follow-up, most patients gained
      weight (n = 19), took calcium supplements (n = 16), and exercised regularly (n =
      22), but fewer than half reached 80% or more of ideal body weight (n = 11),
      resumed menses (n = 6), or received estrogen (n = 4). Cortical bone density was
      stable during follow-up for the group as a whole; the mean annual change (+/- SD)
      was +0.005 (+/- .015) g/cm2 (95% confidence interval, -0.0009 to +0.0109). There
      was no significant difference in the mean change in bone density between women
      who attained 80% of ideal weight and those who did not or between groups who did
      or did not regain menses, take estrogen or calcium, or exercise vigorously. Four
      fractures were clinically observed in three women during follow-up. The rate of
      0.05 nonspine fractures per person-year (95% confidence interval, 0.02 to 0.13)
      exceeds that of normal women in this age range (relative risk, 7.1; 95%
      confidence interval, 3.2 to 18.5). We conclude that reductions in cortical bone
      density appear not to be rapidly reversed by recovery from anorexia nervosa and
      that anorectic women may have an increased risk of fracture.

PMID- 1996001
TI  - Cardiomyopathy associated with the smoking of crystal methamphetamine.
AB  - The smoking of crystal methamphetamine, or "ice," is a growing drug abuse problem
      in the United States. The toxic effects of methamphetamine smoking have not been
      well described. We describe two patients with cardiovascular toxic effects
      associated with the smoking of crystal methamphetamine. In our first patient, the
      use of smokeable methamphetamine was associated with the subsequent development
      of pulmonary edema and a dilated cardiomyopathy. In our second patient, the
      smoking of crystal methamphetamine likely produced diffuse vasospasm that
      resulted in acute myocardial infarction, cardiogenic shock, and death. The
      recognition of potentially lethal cardiac complications associated with the
      smoking of crystal methamphetamine is of extreme significance and should be
      emphasized to potential abusers of this drug.

PMID- 1996000
TI  - The effect of standard- and high-dose epinephrine on coronary perfusion pressure
      during prolonged cardiopulmonary resuscitation.
AB  - We studied the effect of standard and high doses of epinephrine on coronary
      perfusion pressure during cardiopulmonary resuscitation in 32 patients whose
      cardiac arrest was refractory to advanced cardiac life support. Simultaneous
      aortic and right atrial pressures were measured and plasma epinephrine levels
      were sampled. Patients remaining in cardiac arrest after multiple 1-mg doses of
      epinephrine received a high dose of 0.2 mg/kg. The increase in the coronary
      perfusion pressures was 3.7 +/- 5.0 mm Hg following a standard dose, not a
      statistically significant change. The increase after a high dose was 11.3 +/-
      10.0 mm Hg; this was both statistically different than before administration and
      larger than after a standard dose. High-dose epinephrine was more likely to raise
      the coronary perfusion pressure above the previously demonstrated critical value
      of 15 mm Hg. The highest arterial plasma epinephrine level after a standard dose
      was 152 +/- 162 ng/mL, and after a high dose, 393 +/- 289 ng/mL. Because coronary
      perfusion pressure is a good predictor of outcome in cardiac arrest, the increase
      after high-dose epinephrine may improve rates of return of spontaneous
      circulation.

PMID- 1996002
TI  - Medical diagnostic ultrasound instrumentation and clinical interpretation. Report
      of the ultrasonography task force. Council on Scientific Affairs.
AB  - Over the past 20 years, there has been a dramatic increase in the use of
      ultrasonography as an imaging modality. The introduction of real-time
      ultrasonography and Doppler units for the measurement of blood flow in the 1970s,
      recent advances in transducer design, signal processing, and miniaturization of
      electronics, along with the lack of radiation exposure, have been primarily
      responsible for the increased use of ultrasound. However, although
      ultrasonography can provide diagnostic information safely and easily,
      interpretation of the information requires an understanding of the physics behind
      ultrasound, how that physics is translated into ultrasound instrumentation,
      recognition of artifacts that are associated with the various types of
      ultrasonography, and identification of these artifacts in specific anatomic
      locations.

PMID- 1996003
TI  - High-dose epinephrine during resuscitation. A word of caution.

PMID- 1996005
TI  - Infant head shaping.

PMID- 1996006
TI  - Radiation proctitis: therapy and prognosis.

PMID- 1996007
TI  - Risky business: needlesticks in residency.

PMID- 1996008
TI  - A medical career: idealism and reality.

PMID- 1996009
TI  - The competitive edge.

PMID- 1996010
TI  - The rite of spring.

PMID- 1996011
TI  - Sexual assault nurse examiners: a SANE way to care for rape victims.

PMID- 1996012
TI  - Heparin locks for emergency department patients.

PMID- 1996013
TI  - Postsplenectomy sepsis: a case review and one hospital's campaign to prevent
      other needless tragedies.

PMID- 1996014
TI  - Are health care providers satisfied with the current advanced cardiac life
      support course?

PMID- 1996015
TI  - Pediatric trauma patients: differences and implications for emergency nurses.
AB  - Caring for the pediatric trauma patient can be one of the most difficult and
      rewarding challenges an emergency nurse faces. Being aware of sources of trauma,
      understanding growth and development and the differences between the adult and
      pediatric patient, keeping the appropriate equipment for pediatric resuscitation,
      and being prepared emotionally ensure that the needs of the pediatric trauma
      patient can be better met in any emergency department.

PMID- 1996016
TI  - A nurse's guide to recruitment ads.

PMID- 1996017
TI  - President's message. Global collegiality in emergency nursing.

PMID- 1996018
TI  - Administering methylprednisolone for acute spinal cord injuries.

PMID- 1996019
TI  - One opinion on the importance of keeping the same advanced cardiac life support
      course for all providers.

PMID- 1996020
TI  - Missed myocardial infarction: violation of federal law?

PMID- 1996021
TI  - An educational plan for the orientation of emergency nurses.

PMID- 1996022
TI  - How to deal with children in the emergency department.

PMID- 1996023
TI  - A 36-year-old woman with a three-week history of epigastric pain, nausea, and
      vomiting.

PMID- 1996025
TI  - Music?

PMID- 1996024
TI  - On walking into walls and finding windows. Interview by Marlene Jezierski.

PMID- 1996026
TI  - The last tear.

PMID- 1996027
TI  - Maintaining nursing autonomy: one emergency department's success.

PMID- 1996028
TI  - More on nasal vs. oral suctioning in newborn infants.

PMID- 1996029
TI  - Promoting a positive image of emergency nursing within the hospital.

PMID- 1996030
TI  - A 39-year-old man with acute hemolytic crisis secondary to intravenous injection
      of hydrogen peroxide.
AB  - The diagnosis of cancer or its recurrence is often emotionally devastating for
      patients and those close to them. People may have a great deal of difficulty
      accepting the diagnosis and may seek others' opinions about the best course of
      treatment. When a physician projects that there is no hope, or if a cure is no
      longer probable, the patient and those close to him or her may feel helpless and
      hopeless. Given the resultant psychologic turmoil, the patient may be led to try
      unproven methods. Such methods, often referred to as "cancer quackery," represent
      a person's attempt to reassert personal control in response to these feelings of
      helplessness and hopelessness. Cancer quackery involves about $2 billion each
      year in the United States alone. One study demonstrated that approximately 39% of
      the pediatric outpatients studied had either tried, considered, or received
      recommendations for unproven methods of cancer treatment. Laetrile and faith
      healing were the most frequent methods used. One of the most recent of the
      unproven methods of cancer treatment that have been shown to cause life
      threatening complications is IV injection of hydrogen peroxide. The scientific
      rationale behind this procedure is still unclear, but the side effects are
      clearly life threatening.

PMID- 1996031
TI  - Definitions, classification, and clinical presentation of urinary tract
      infections.
AB  - Urinary tract infections encompass a spectrum of clinical and pathologic
      conditions involving various parts of the urinary tract. Each syndrome has its
      own unique epidemiology, natural history, and clinical manifestations. Basic
      terminology used in describing urinary tract infections is defined in this
      article. A classification of these infections and their clinical features is
      presented.

PMID- 1996032
TI  - Bacterial etiologic agents in the pathogenesis of urinary tract infection.
AB  - Most of the information available concerning virulence factors of uropathogens is
      based on studies of Escherichia coli, the commonest cause of urinary tract
      infections. Earlier studies revealed several phenotypic Escherichia coli
      virulence factors that influenced both the anatomic level and severity of urinary
      tract infection. Virulence factors included O antigen serotype, presence and
      quantity of K capsular polysaccharide, adherence to uroepithelial cells,
      resistance to serum bactericidal activity, hemolysin, and aerobactin production.
      The introduction of DNA hybridization methodology has provided a valuable tool
      for reevaluation of the epidemiology of Escherichia coli infection as well as an
      alternative to the conventional phenotypic approach for studying the genotypic
      basis for virulence.

PMID- 1996033
TI  - Host defense mechanisms in the pathogenesis of urinary tract infection.
AB  - Certain microorganisms have a propensity for causing urinary tract infection, and
      the route (either ascending or hematogenous) by which microorganisms contaminate
      the urinary tract from external sources is frequently characteristic of the
      microorganism. There are local defense mechanisms both in the urine and at each
      anatomic site in the urinary tract (urethra, bladder, ureter, and kidney). The
      defense mechanisms at one site may have opposing effects on microbial growth at
      other sites in the urinary tract. The outcome following entrance of
      microorganisms into the urinary tract is a result of competing forces, which
      consist of these local urinary defense mechanisms, the initial numbers of
      microorganisms contaminating the urinary tract, and microbial virulence factors.

PMID- 1996034
TI  - Epidemiology and natural history of urinary tract infections in children.
AB  - Recent retrospective surveys have supported previous investigations in
      demonstrating the incidence of UTI during infancy; 0.3% to 1.2% of infants
      develop symptomatic UTI during the first year of life. Boys are more commonly
      infected during the first 3 months of life. After the first year, symptomatic UTI
      is much more frequent among girls. Similarly, asymptomatic bacteriuria is more
      frequently detected in boys than in girls during the first 12 months of life.
      Thereafter, the incidence decreases markedly in boys but increases in girls.
      Recent investigations indicate that lack of circumcision is a risk factor for UTI
      among male infants. Recurrent UTI is common and frequently asymptomatic. The most
      important microbiologic factor that is associated with E. coli causing acute
      pyelonephritis is adherence mediated by P fimbriae. Other factors, such as
      capsule, lipopolysaccharide, aerobactin production, and serum resistance, also
      determine the invasiveness of E. coli. Vesicoureteral reflux appears to be an
      important host factor predisposing to UTI. Microbiologic and host factors that
      are determinants of renal scarring are under investigation.

PMID- 1996035
TI  - The natural history of urinary infection in adults.
AB  - The vast majority of otherwise healthy adults with anatomically and functionally
      normal urinary tracts experience few untoward long-term consequences from
      symptomatic or asymptomatic UTIs. Effective early treatment of symptomatic
      infection rapidly curtails bacterial invasion and the resulting inflammatory
      response. Rarely, uncomplicated acute pyelonephritis causes suppuration and renal
      scarring. Urinary infections in patients with renal calculi, obstructed urinary
      tract, neurogenic bladder, or diabetes are frequently much more destructive and
      have ongoing sequelae. Strategies to treat both the infection and the
      complications are often necessary to alter this outcome.

PMID- 1996036
TI  - Laboratory in the diagnosis and management of urinary tract infections.
AB  - The laboratory is essential in the diagnosis and management of UTIs. The presence
      of pyuria and bacteriuria, the two most important indicators of UTIs, are most
      accurately determined by standard techniques. In quantitating pyuria, the finding
      of greater than or equal to 10 leukocytes/mm3 of urine by either hemocytometry or
      direct microscopy correlates highly with symptomatic, culture-proven UTIs. The
      determination of bacteriuria by direct microscopy is inaccurate, particularly at
      lower levels of bacteriuria; thus, quantitative urine cultures remain the most
      accurate measure of bacteriuria. Significant bacteriuria, previously defined as
      greater than or equal to 10(5) CFU/ml of urine, has been redefined with the
      observation that as few as 10(2) CFU/ml can be associated with significant pyuria
      and symptoms suggestive of cystitis. The need for routine and posttreatment urine
      cultures in nonpregnant women with acute dysuria remains controversial, but
      current data suggest that they are usually unnecessary. Rapid diagnostic tests
      for detection of pyuria and bacteriuria are designed to increase efficiency and
      decrease cost in the diagnosis of UTI. Unfortunately, none of these techniques
      can quantitate pyuria or bacteriuria as accurately as the standard methods, but
      the level of accuracy offered by the standard methods is not always necessary in
      the care of patients with uncomplicated UTIs. These tests are particularly well
      suited for screening asymptomatic high-risk populations. Noninvasive localization
      techniques continue to be explored as possible alternatives to invasive
      localization procedures, but they remain largely research tools that are not
      readily available to the practicing clinician. Understanding the applicability
      and appropriate use of newer technologies in the evaluation of patients with UTIs
      and how these technologies complement the standard diagnostic techniques will
      lead to better, more efficient, and less costly patient care.

PMID- 1996037
TI  - Management of urinary tract infections in children.
AB  - Urinary tract infection is common in children. The presentation varies with age.
      Younger children exhibit protean signs. Diagnosis is dependent on the
      demonstration of significant bacteriuria in a properly collected and handled
      urine sample. The approach to treatment depends on the degree of illness at
      presentation, the presence of structural urinary tract abnormalities, and the age
      of the patient. Pathophysiology of urinary tract infection is dependent on
      interactive factors of the host and of the invading microorganism. Urinary tract
      abnormalities have significant impact on the management of children with urinary
      tract infections, both medically and surgically. Of particular importance is the
      observation that renal damage usually occurs within the first 5 years of life,
      and treatment delay in some young patients may have significant consequences. The
      overall prognosis in children with urinary tract infection is favorable.

PMID- 1996038
TI  - Management of acute uncomplicated urinary tract infection in adults.
AB  - Acute uncomplicated UTI is one of the most common problems for which young women
      seek medical attention, and it accounts for considerable morbidity and health
      care costs. Acute cystitis is a superficial infection of the bladder mucosa,
      whereas pyelonephritis involves tissue invasion of the upper urinary tract.
      Localization tests suggest that as many as one third of episodes of acute
      cystitis are associated with silent upper tract involvement. Acute cystitis or
      pyelonephritis in the adult patient should be considered uncomplicated if the
      patient is not pregnant or elderly, if there has been no recent instrumentation
      or antimicrobial treatment, and if there are no known functional or anatomic
      abnormalities of the genitourinary tract. Most of these infections are caused by
      E. coli, which are susceptible to many oral antimicrobials. Because of the
      superficial nature of cystitis, single-dose and 3-day regimens have gained wide
      acceptance as the preferred methods of treatment. Review of the published data
      suggests that a 3-day regimen is more effective than a single-dose regimen for
      all antimicrobials tested. Regimens with trimethoprim-sulfamethoxazole appear to
      be more effective than those with beta-lactams, regardless of the duration. Acute
      pyelonephritis does not necessarily imply a complicated infection. Upper tract
      infection with highly virulent uropathogens in an otherwise healthy woman may be
      considered an uncomplicated infection. The optimal treatment duration for acute
      uncomplicated pyelonephritis has not been established, and 14-day regimens are
      often used. We prefer to use antimicrobials that attain high renal tissue levels,
      such as trimethoprim-sulfamethoxazole or quinolones, for pyelonephritis. Women
      with frequently recurring infections can be successfully managed by continuous
      prophylaxis, either daily or thrice-weekly, by postcoital prophylaxis, or, in
      compliant patients, by early self-administration of single-dose or 3-day therapy
      as soon as typical symptoms are noted. Our drug of choice for all these regimens
      is trimethoprim-sulfamethoxazole. Acute uncomplicated cystitis in adult men is
      very uncommon, but it is occasionally noted in homosexual men who practice
      insertive and intercourse or in heterosexual men whose partners have vaginal
      colonization with E. coli.

PMID- 1996039
TI  - Epidemiology, natural history, and management of urinary tract infections in
      pregnancy.
AB  - The urinary tract undergoes profound physiologic and anatomic changes during
      pregnancy that facilitate the development of symptomatic UTIs in women with
      bacteriuria. Although the adverse effects of asymptomatic bacteriuria on maternal
      and fetal health continue to be debated, it is clear that asymptomatic
      bacteriuria is the major risk factor for developing symptomatic UTI and that
      symptomatic infections are associated with significant maternal and fetal risks.
      Because the majority of symptomatic UTIs develop in women with bacteriuria
      earlier in pregnancy, treatment of bacteriuria is undertaken to prevent
      symptomatic infections. All women should be screened at the first antenatal
      visit, which is reliably and inexpensively done with a dipstick culture. Short
      course therapy is as effective as prolonged therapy and should be followed with a
      repeat culture to document clearing of the bacteriuria. Failure to eliminate
      bacteriuria with repeated therapy or recurrence with the same organism is
      indicative of renal parenchymal infection or a structural abnormality. All women
      with persistent bacteriuria or recurrent infection should have follow-up cultures
      and a complete urologic evaluation after delivery.

PMID- 1996040
TI  - Special problems of urinary tract infection in the elderly.
AB  - Bacteriuria is much more common among elderly than among younger populations, and
      is most often asymptomatic. Asymptomatic bacteriuria in the elderly is a benign
      condition in the vast majority of cases and does not require therapy. When
      symptomatic lower UTI occurs, short-course (3-day) therapy with any of several
      agents is indicated, and is usually effective. Women with frequently recurrent
      symptomatic UTI may benefit from estrogen therapy. Fourteen days of therapy is
      indicated in patients with upper UTI. The typical signs and symptoms of
      pyelonephritis may be altered or absent in elderly patients.

PMID- 1996041
TI  - Urinary tract infection in the impaired host.
AB  - In general, defects in phagocytosis and in humoral or cellular immunity do not
      appear to predispose to the acquisition of UTI but do influence the clinical
      manifestations and the severity, microbiology, and complications of infection
      once it is established. The incidence of UTI in immunosuppressed patients other
      than diabetics or renal transplant recipients is not higher than the incidence in
      nonimmunosuppressed individuals. The higher frequencies of infection seen in
      diabetics and in renal transplant recipients correlate best with the duration of
      bladder instrumentation rather than with glycosuria or immunosuppressive regimen.
      Neutropenia blunts the clinical manifestations of UTI and predisposes to
      bacteremia. Use of broad spectrum antibiotics results in alterations in
      indigenous flora, promotes urinary infections with resistant nosocomial
      pathogens, and predisposes to fungemia with hematogenous seeding of the urinary
      tract. Routine screening for detection of asymptomatic bacteriuria and prompt
      institution of antimicrobial therapy is indicated only in renal transplant
      recipients within 3 months of their surgery and not in any of the other diseases
      discussed.

PMID- 1996042
TI  - Prostatitis.
AB  - Several distinct types of prostatitis, or prostatitis syndromes, are now
      recognized. The most common forms include acute and chronic bacterial
      prostatitis, nonbacterial prostatitis, and prostatodynia. Bacterial prostatitis,
      caused mainly by coliform bacteria, Pseudomonas, and Enterococcus faecalis, is
      often difficult to cure and usually requires extended therapy (4-16 weeks) with
      an appropriate antimicrobial agent that achieves therapeutic levels in the
      prostatic secretory system. About 90% of men with prostatitis have nonbacterial
      prostatitis or prostatodynia. Nonbacterial prostatitis is an inflammation of the
      prostate of unknown cause. Patients with prostatodynia typically have sterile
      cultures and normal prostatic secretions but demonstrate an acquired voiding
      dysfunction on videourodynamic testing. Because nonbacterial types of prostatitis
      have no recognized infectious cause, treatment using antimicrobial agents is
      ineffective and unwarranted.

PMID- 1996043
TI  - Radiology of renal infection.
AB  - Radiology plays a key role in the diagnosis and treatment of renal inflammatory
      diseases. The efficacious use of the various imaging modalities in evaluating
      renal inflammatory disease requires knowledge of their attributes as well as
      their weaknesses. We review the available studies and use of contrast agents, and
      illustrate radiologic findings in specific inflammatory disease processes.

PMID- 1996044
TI  - The role of the urologist in urinary tract infection.
AB  - The urologist's role in urinary tract infections will vary according to the
      situation. Urologists do give primary care, consult, define anatomic
      abnormalities, surgically correct abnormalities, and do basic research in the
      field of urinary tract infections. Urologists are essential in diagnosing and
      managing cases with infections behind obstructions and working out the
      differential diagnoses of chronic prostatitis.

PMID- 1996045
TI  - The catheter and urinary tract infection.
AB  - Catheter-associated bacteriuria is the most common infection acquired in
      hospitals and nursing homes. This infection would be even more common but for the
      use of the closed catheter system. Most modifications have not improved upon the
      closed catheter itself. However, even with meticulous care, this system will not
      prevent bacteriuria forever. After bacteriuria develops, our ability to limit its
      complications is minimal. Additionally, the catheterized urinary tract becomes a
      reservoir of bacteria that can be transferred to other patients. Once a catheter
      is put in place, one must keep two important concepts in mind: (1) keep the
      catheter system closed in order to postpone the onset of bacteriuria; and (2)
      remove the catheter as soon as possible. If the catheter can be removed before
      bacteriuria develops, postponement becomes prevention. However, the best
      prevention is not to use a urethral catheter at all. Non-device alternatives to
      urethral catheterization should be used whenever possible. If these are not
      useful or successful, then other devices might be considered. For incontinent
      men, a condom catheter is a useful alternative. For patients with urinary
      retention, intermittent or suprapubic catheterization may be options for both
      short-term and long-term needs. The roles of these alternatives to urethral
      catheters must be defined by controlled trials.

PMID- 1996046
TI  - Urinary tract infection: economic considerations.
AB  - Urinary tract infection results in significant morbidity and mortality while
      consuming large amounts of national resources. The prevention, diagnosis, and
      treatment of urinary tract infection produce both costs and benefits, and
      economic analysis provides a rational framework for looking at these effects. The
      goals and methods of economic analysis in medicine are summarized, and strategies
      to address uncomplicated cystitis, nosocomial urinary tract infection, and
      pyelonephritis are reviewed, with an emphasis on the economic trade-offs faced by
      decision makers.

PMID- 1996047
TI  - [Pleural lesions in patients with Hodgkin's disease with pulmonary involvement].
AB  - A retrospective study of 334 primary patients with Hodgkin's disease with the
      affected mediastinal lymph nodes and pulmonary tissue (stages IIE, IV) was
      carried out. Pleural affection was detected in 280 (88.8%) patients. Limited
      pleural affection resulting from contact dissemination from the enlarged lymph
      nodes was shown to make no effect on prognosis. Generalized involvement of the
      pleura was shown to deteriorate considerably a course of disease in patients with
      contact (localized) pulmonary involvement and to have no prognostic importance in
      disseminated involvement.

PMID- 1996049
TI  - [Radiation modifying effect of hyperglycemia: correlation between glucose dose
      and tumor size].
AB  - Experiments were made on rats with transplantable sarcoma-45 and sarcoma M-1.
      Dose correlation was established during a study of hyperglycemic radiomodifying
      action. Glucose injection at a dose of 6-17.5 g/kg was shown to enhance
      irradiation action. Glucose injection below or above these doses might cause
      worse radiotherapy results or even the death of animals. The best effect was
      obtained with small-size tumors. Large tumors (over 2 cm3) were less sensitive to
      hyperglycemia combined with irradiation. Skin radioprotective action of
      hyperglycemia before irradiation increased with an increase in a dose. The
      authors proposed a method of radioprotective action of hyperglycemia on normal
      tissues, enhancing simultaneously the antitumor effect of irradiation.

PMID- 1996048
TI  - [Contact radiotherapy in rheumatoid lesions of the knee joint using Au-198].
AB  - An instrumental-calculation method of assessment of an absorbed dose of radiation
      in the synovial tissue of the knee joint in radionuclide therapy with 198Au using
      directly measured topometric parameters was used for patients with rheumatoid
      arthritis. A group of 294 knee joint of 138 patients was considered by way of a
      retrospective analysis. Dosimetric indices in all cases (except stage IV
      arthritis) showed values which were not contrary to clinical assessment of the
      patients: status after therapy.

PMID- 1996050
TI  - [Dosimetric computer-assisted planning of therapy of malignant tumors with fast
      neutron beam of cyclotron U-120].
AB  - A method program were developed for computation of dosimetric characteristics of
      radiation fields in gamma-neutron irradiation of cancer patients. The program
      provided calculation of the distribution of isoeffective and absorbed doses and
      the time-dose-fractionation factor. Isodose charts could be obtained in the
      digital code or graphically.

PMID- 1996051
TI  - [Neutrophil and lymphocyte dose curves in relatively uniform human whole body
      irradiation (based on data of the accident at the Chernobyl AES)].
AB  - The authors have summed up the experience in a study of regularities of the bone
      marrow syndrome in persons exposed to rather homogeneous gamma-beam irradiation
      during the accident at the Chernobyl Nuclear Power Station (127 cases).
      Hematological data were processed by computer, and empiric dose curves of
      neutrophils and lymphocytes were obtained within the range of 0.5-12 Gy by
      regressive analysis. These curves were compared with the previous data on the
      time course of these cells after whole-body irradiation. New data were obtained
      on the nature of a course of a granulocyte recovery phase at a dose level over 5
      Gy. Some features of the time course of lymphocytes in persons exposed to
      radiation during the accident at the Chernobyl Nuclear Power Station, were
      considered.

PMID- 1996052
TI  - [Cytogenetic effect of small doses of tritium beta irradiation].
AB  - The effect of tritium beta-radiation within the dose range of 0.5 x 10(-3) = 0.6
      Gy on human blood lymphocytes in vitro was investigated. Dose-effect correlation
      was determined by the frequency of aberrant cells and the sum of chromosome
      aberrations per 100 cells. As compared to a rated curve corresponding to a linear
      quadratic model y = a + bD + cD2, experimental curves (showing correlation
      between cytogenetic indices and a dose) are of abnormal nature with a plateau in
      a dose range less than 7.5 x 10(-2) Gy. A big confidence interval of cytogenetic
      effect indices in a dose range less than 7.5 x 10(-2) Gy was shown to be
      determined by the number of analyzed metaphases. The proof of significance of a
      plateau on a dose-effect curve in regions of small doses (e.g. with a confidence
      interval of +/- 24%) necessitated analysis of no less than 10,000 metaphases per
      dose.

PMID- 1996053
TI  - [Effects of the dose on the prognosis of dynamics of blood neutrophil count based
      on cytogenetic analysis of lymphocytes of victims of the Chernobyl AES accident].
AB  - The authors investigated prognostic significance of irradiation intensity with
      relation to the severity of a course of the bone marrow syndrome in the affected
      population at the Chernobyl accident. Absorbed doses were determined by analysis
      of lymphocyte chromosome aberrations and the time course of the blood neutrophil
      count. The evaluation of the severity of blood disorders by cytogenetic and
      hematological tests was shown to coincide in 85% of patients. Due to lack of
      information on irradiation physical data, an absorbed dose mean rate was assessed
      for the entire period of stay in the high radiation zone. In 81 patients mean
      dose rate values varied within 0.1-22 Gy/h. Further analysis has shown that a
      mean dose rate value in this range did not influence the prognosis of a course of
      the bone marrow syndrome in the affected persons (by the results of cytogenetic
      investigation of lymphocyte cultures).

PMID- 1996054
TI  - [Program of long-time immunologic monitoring of population groups exposed to risk
      factors at the Chernobyl AES radiation accident].

PMID- 1996055
TI  - [Metastasis to the vascular tunic of the eye].
AB  - The author has summed up his experience in the diagnosis and radiation therapy of
      6 patients with breast cancer (5) and lung cancer metastases to the vascular coat
      of the eye. The initial and leading symptoms are increasing impairment of vision.
      In 3 patients metastases to the eye developed against a background of tumor
      generalization. gamma-beam therapy at a total focal dose of 30 Gy within 10 days
      of irradiation improved vision in 4 patients.

PMID- 1996056
TI  - [Shielding of the adjacent organs in radiotherapy of cervical cancer on AGAT-B
      apparatus].
AB  - Elastic screens can be used to reduce by approximately 30% radiation exposure of
      the bladder and rectum in the intracavitary component of combined radiotherapy of
      cervical cancer. These screens are sealed polyethylene parcels, filled in with
      tungsten powder. The literature data show that they make it possible to avoid
      radiation reactions of the bladder, not reducing the efficacy of radiation
      exposure of a tumor. Rectum protection is weaker.

PMID- 1996057
TI  - [Diagnostic effectiveness of mammography in various age groups].
AB  - The diagnostic efficacy of 935 mammographies from the mammology service for self
      referred symptomatic women was assessed for the period of 1975-1988. Breast
      cancer was detected in 200 women. The paper is concerned with the distribution of
      true- or false-positive and true- or false-negative mammographic diagnoses in the
      age groups of women under 40, 40 to 49 and over 49. The sensitivity of
      mammography in these age groups was 87.5, 72.4 and 89%, the specificity was 83.5,
      76.4 and 83%, and the positive predictive values were 42, 38.2 and 69.5%,
      respectively.

PMID- 1996058
TI  - [Suspected sizable (focal) formation in the kidney].

PMID- 1996059
TI  - [Organization of the workplace for a physician specialist in ultrasonic
      diagnosis].

PMID- 1996060
TI  - [Small doses of ionizing radiation].

PMID- 1996061
TI  - [Transvaginal ultrasonography in the assessment of local extension of rectal
      cancer].
AB  - To explore potentialities of transvaginal sonography in the diagnosis of rectal
      tumors 33 female patients were examined. Transvaginal sonography was shown to be
      optimum for accurate local staging of rectal tumors. The overall staging accuracy
      for transvaginal sonography in this study was 94%. There were one understaged and
      one overstaged cases. Pathological pararectal lymph nodes were detected in 57.5%
      of the patients.

PMID- 1996062
TI  - [On the way to computer-assisted instruction].

PMID- 1996063
TI  - [Possibilities of radiotherapy in improving the treatment results in patients
      with colon cancer].

PMID- 1996064
TI  - [Computerized tomography in the planning of radiotherapy of prostatic cancer].
AB  - The paper is devoted to the description of methods of topometric preparation of
      73 prostatic cancer patients for gamma-and proton-beam irradiation using an x-ray
      simulator and a CT tomograph. Basing on the measurement of the prostate in 3
      directions in patients with different stages of disease (T1-2-24, T3-29 and T4
      20), a conclusion was made that a prostate size was not enough to determine a
      stage of disease though a tendency to an increase in prostate size corresponded
      to the growing T index. However, stages T1-2 and T4 could be determined for sure
      within a certain range of prostate size values.

PMID- 1996065
TI  - [Preventive treatment of local radiation injuries in combined radiotherapy of
      rectal cancer].
AB  - Preventive therapy of local radiation injuries was conducted in 46 patients with
      inoperable rectal cancer during a course of combined radiotherapy after a radical
      program. Preventive therapy of local radiation injuries included a general action
      drug and a local use of ethonium. This course of radiotherapy after a radical
      program with the delivery of doses up to 90-95 Gy resulted in the reduction of
      the number of late local radiation injuries.

PMID- 1996066
TI  - [Morphometric analysis of regression of breast cancer after radiotherapy and
      thermoradiotherapy].
AB  - A study was made of 50 infiltrating breast carcinomas, stages II-III, treated
      with a combined method with or without local UHF-hyperthermia. The object of
      investigation were cytological and histological specimens, histotopographic tumor
      slices. Methods of mathematical analysis of correlations between tumor tissue
      regression and parameters of parenchymal differentiation in cytological specimens
      and an area of tumor nodes were employed. Tumor tissue regression and
      differentiation of cell elements in cytological specimens showed correlation in
      the course of combined treatment on the basis of radiotherapy. Insignificant
      correlation was revealed between a volumetric density of the tumor parenchyma,
      preserved after combined treatment with UHF-hyperthermia, and parameters of cell
      differentiation in cytological specimens. Significantly positive correlation was
      found between an area of tumor nodes and an area of necrotic foci, developing in
      them after thermoradiotherapy.

PMID- 1996067
TI  - [Peripheral blood indices in various therapeutic methods used in Hodgkin's
      disease].

PMID- 1996068
TI  - [Effects of short-term hyperglycemia on the state of brain function in patients
      with neurological neoplasms].
AB  - The paper is concerned with the results of investigation of the effect of short
      term hyperglycemia on main cerebral functions in neuro-oncological patients.
      Clinical and paraclinical control in the course of investigation revealed
      insignificant and transient changes of the neurological status, ECG and
      investigated cerebral functions. In a lesser group of patients changes over time
      were unobserved. Taking into account good tolerance of short-term hyperglycemia
      and the results of its effective use in general oncology, one can recommend it as
      a modifier in radiation therapy of brain gliomas. Proceeding from the obtained
      experimental data on a similar tumor model as well as positive results of the use
      of short-term hyperglycemia in general oncology, its use appeared to be most
      effective after tumor irradiation. Taking into account a certain degree of
      unreliability of the method (catheterization of the subclavicular vein),
      requiring strict control on the part of medical personnel, the use of short-term
      hyperglycemia could be effectively implemented during large-fractionated
      irradiation of brain gliomas.

PMID- 1996069
TI  - [Combined transparietal method in the evaluation of microcirculation,
      angioarchitectonics and morphology of the liver].
AB  - A method of transcutaneous transhepatic injection hepatography with local fine
      needle anesthesia was developed. Its informative value is shown in investigations
      of the intrahepatic veins, lymphatic system and their interrelationships at the
      sinusoidal level. The method is noninvasive and can be performed in a therapy
      department. Injection hepatography can be followed by liver biopsy in the same
      liver segment. The quality of investigation increases with the use of an
      attachment for computerized radiography.

PMID- 1996070
TI  - [Establishing of doses from the internal irradiation for the personnel of the
      Chernobyl AES and persons detailed in 1986-1987].
AB  - The paper is concerned with the results of measurements of characteristics of the
      air media in the zone of the damaged reactor as with the assessment of doses from
      internal irradiation on the basis of calculations of air media parameters and the
      results of actual measurements of the uptake and content of radionuclides in the
      personnel of the Chernobyl Nuclear Power Station and persons sent on mission
      there in 1986-1987, the results being obtained by indirect and direct biophysical
      methods of control of internal irradiation. The calculated data are well in
      accord with the results of actual measurements of the contents of radionuclides
      in the body. Internal irradiation of all tissues and organs, determined by the
      inhalation of a mixture of radionuclides, worked almost completely within the
      first year following the accident, the thyroid being the critical organ. In the
      next years internal irradiation for the personnel of the Chernobyl Nuclear Power
      Station was determined entirely by transuranic elements and was about 0.1 M.P.D
      annually for bone tissue. The value of a mean effective equivalent dose from
      internal irradiation in 50 years is 85 mSv for professionals, and a contribution
      of internal irradiation to the whole-body one over the first well as is 13%.

PMID- 1996071
TI  - [Ultrasonographic symptoms of portal hypertension].
AB  - Ultrasound investigation was performed in 49 patients with the syndrome of portal
      hypertension. A portal blood flow blockade level could be determined by the type
      of changes of the abdominal and hepatic vessels. Portal hypertension of
      intrahepatic type was characterized by the dilated portal and splenic veins and
      the hepatic artery. The intrahepatic branches of the portal vein were amputated.
      Prehepatic blockade was diagnosed on the basis of local narrowing of the portal
      vein by a sizable formation, liver vascularization was unnoticed. A suprahepatic
      block was unaccompanied by a dramatic change in the lumens of the portal and
      splenic veins and the hepatic artery. A conclusion was made that real time
      ultrasound investigation could provide important information on differential
      diagnosis of the causes of a portal block. As a noninvasive and harmless method
      it should play a leading role in hepatological practice.

PMID- 1996072
TI  - [Thyroid irradiation doses and organization of endocrinological monitoring of the
      inhabitants of the Ukrainian S.S.R. after the accident at the Chernobyl AES].
AB  - The paper is devoted to one of the most important aspects of the accident at the
      Chernobyl Nuclear Power Station: thyroid irradiation in the residents of 8 areas
      in the Ukrainian SSR and the town of Pripyat, affected with radioactive iodine.
      Irradiation doses, prognosis of medical effects of the accident, methods and
      practical measures for the organization of endocrinological monitoring of the
      affected population were thoroughly considered. The authors proposed a scheme of
      health care of the population in these areas. They also discussed the structure
      of data bases for analysis of medico-dosimetric information on "iodine" effects
      of the accident. The main trends in medico-dosimetric problems of the effects of
      thyroid irradiation were outlined.

PMID- 1996073
TI  - [Effects of pentacin on subcellular distribution of Pu-239 nitrate in the lungs
      of rats].
AB  - The method of differential centrifugation has shown that 26% of 239Pu-nitrate
      injected intratracheally, is detected in cells in 3 h (24.4% of Pu is bound with
      subcellular organellae). In 24 h the nuclear fraction acquires a paramount
      importance in Pu binding. In the hyaloplasm 239Pu is distributed equally between
      low molecular (32.9-42.9%) and high molecular (54.1-55.2%) proteins. Pentacine
      decreases the level of Pu in the lungs, in the sum of subcellular fractions and
      in the sum of organellae, but produces no noticeable action on the level of the
      radionuclide in hyaloplasmic proteins though promotes certain redistribution of
      the radionuclide between low- and high molecular proteins.

PMID- 1996074
TI  - [Genome of somatic cells of animals during prolonged radiation exposure].
AB  - The genome of the thymus and bone marrow of the Wistar rat brain was investigated
      during daily repeated irradiation at a dose of 0.5 Gy in total doses of 0.5-20
      Gy. The genome was assessed by a number of tests characterizing the high and low
      levels of DNA structural organization. Analysis was performed one day after the
      last fraction of irradiation. Stable changes in the primary DNA structure of
      thymocytes were shown by a decrease in the content of double-strand DNA using
      spectrofluorimetry. Changes in the primary DNA structure of the bone marrow were
      undetectable. Prolonged irradiation led to the formation of conformation changes
      in the nucleoid of cells of both tissues detectable by viscosimetric and
      spectrofluorimetric methods.

PMID- 1996075
TI  - [A gamma spectrometer for measurements of radionuclide concentrations in
      biological samples].
AB  - A CAMAC spectrometer with a scintillation detector was developed for
      radioactivity measurements in environmental and biological samples. The
      spectrometer allows one to use an additional single channel analyser for rapid
      isotope control and to use simultaneously a number of ADCs in a concurrent mode.
      A technique of efficiency calibration is described which simulates the volume
      sample measurement with a point reference source of photon radiation and a
      cylindrical water-equivalent plate-stack phantom. The minimum detectable
      radionuclide concentration was found to be equal 5.10(-5) Ci/kg.

PMID- 1996076
TI  - [Test control of student knowledge in radiodiagnosis course].
AB  - Various test control tasks to assess the level of self-preparedness for practical
      work in class, knowledge and skills were shown promising for use in the course of
      a study of the fundamentals of radiodiagnosis during control of knowledge of 191
      students of the medical faculty. With the test control the students reached a
      necessary level of knowledge. Therefore the authors recommended to use multistage
      situation problems and test tasks in the course of teaching of combined
      radiodiagnosis.

PMID- 1996077
TI  - [Use of radiosurgical method in the treatment of patients with soft tissue
      sarcoma of the limbs].

PMID- 1996078
TI  - [Radionuclide diagnosis of interstitial pulmonary edema].
AB  - Perfusion scintigraphy of the lungs has shown that a reverse direction of
      postural reactions of the pulmonary blood flow is observed in patients with
      mitral valvular disease: perfusion of the upper lung rather than the lower lung
      increases. It is accounted for by the action of gravitation on capillary
      hydrostatic pressure resulting in the localization of interstitial edema in
      pulmonary venous hypertension mainly in the lower lung, its microcirculatory bed
      being compressed and the blood flow redistributed to the opposite upper lung.
      Therefore successive perfusion scintigraphy of the lungs in the vertical position
      and in the lateral position with a RP administered twice, can serve as a
      sensitive test for diagnosis of interstitial lung edema in various pathological
      conditions.

PMID- 1996079
TI  - [Primary double contrast study of the large intestine using citrate-sorbitol
      barium suspension in the diagnosis of chronic colitis].
AB  - X-ray investigation of the colon was conducted in 292 patients with clinically
      diagnosed chronic colitis: standard 3-phase irrigoscopy-in 189 patients and a
      primary double contrast study of the colon with citrate-sorbitol-barium
      suspension in 103. Basing on x-ray and morphological findings, the diagnosis was
      confirmed in 128 patients of the 1st group (68.2%) and in 89 patients of the 2nd
      group (86%). The primary double contrast study of the colon was found more
      effective as it permitted the detection of elements of the mucosal
      "microcontours": transversal strips, not coinciding with haustration, focal
      granularity, diffuse granularity, small barium suspension "depots" or "niches",
      nodular granularity. It permitted the recommendation of the method for a wide
      clinical use.

PMID- 1996080
TI  - Novel angiotensin II antagonists distinguish amphibian from mammalian angiotensin
      II receptors expressed in Xenopus laevis oocytes.
AB  - Angiotensin II (AII) stimulates rapid increases in cytosolic Ca2+ concentrations
      in Xenopus laevis oocytes after binding to specific receptors located in the
      surrounding follicular cells. In follicular oocytes, the peptide AII receptor
      antagonists saralasin (IC50 = 25 nM) and CGP 42112A (IC50 = 400 nM) were orders
      of magnitude more potent than the non-peptide antagonists DuP 753 and PD-123177
      (IC50 greater than 10 microM) as inhibitors of AII-induced Ca2+ mobilization. The
      relative potencies of the AII antagonists at the Xenopus AII receptor were
      completely different from their activities at the two known mammalian AII
      receptor subtypes. These results indicate that the ligand-binding domain of the
      amphibian AII receptor has a unique conformation that distinguishes with high
      specificity between peptide and non-peptide AII antagonists. The amphibian AII
      receptor is pharmacologically distinct from the AT1 receptor subtype, which
      mediates phosphoinositide hydrolysis and Ca2+ mobilization in mammalian adrenal
      cells.

PMID- 1996081
TI  - Stimulation of nerve growth factor biosynthesis in developing rat brain by
      reserpine: steroids as potential mediators.
AB  - The stimulation of beta-adrenergic receptors by isoproterenol increases nerve
      growth factor (NGF) biosynthesis in C6 rat glioma cells, suggesting that
      norepinephrine may regulate NGF biosynthesis in vivo. We have tested this
      hypothesis in 21-day-old rats by depleting catecholamine stores with reserpine.
      Northern blot analysis of NGF mRNA, in combination with a two-site enzyme
      immunoassay for NGF, showed that depletion of catecholamines was associated with
      a 3-fold increase in NGF mRNA, which was followed by a significant increase in
      the NGF content of cerebral cortex. The increase in NGF mRNA was most marked 9 hr
      after reserpine administration (2 mg/kg, subcutaneously) and was no longer
      apparent 24 hr after drug administration, when brain monoamine stores were still
      depleted. Moreover, the lowest dose of reserpine that significantly increased NGF
      mRNA levels induced only a small change in the content of cortical
      catecholamines. These results suggest that reserpine mediates the increase in NGF
      production by a mechanism other than monoamine depletion. Because reserpine
      increases plasma glucocorticoid concentrations through the pituitary-adrenal
      axis, we investigated whether adrenal steroids could be responsible for the
      induction of NGF biosynthesis. The effect of reserpine on NGF biosynthesis was
      abolished in adrenalectomized rats. Moreover, dexamethasone, a synthetic
      glucocorticoid, given at a dose of 0.5 mg/kg, subcutaneously, increased the
      amount of NGF mRNA and NGF in cerebral cortex. NGF biosynthesis in the central
      nervous system may, thus, be regulated by adrenocortical hormonal secretion.

PMID- 1996082
TI  - Induction of c-jun expression in the myeloid leukemia cell line KG-1 by 1-beta-D
      arabinofuranosylcytosine.
AB  - c-Jun/AP-1 is a transcription factor commonly induced in mammalian cells by
      serum, phorbol compounds, or peptide growth factors. We show that c-Jun/AP-1 is
      inducible as well as coordinately regulated, in the human acute myelogenous
      leukemia cell line KG-1, by the cytostatic drug 1-beta-D-arabinofuranosylcytosine
      (Ara-C). Concomitantly with Ara-C treatment, growth inhibition and loss of
      clonogenic survival of KG-1 cells were observed. Whereas KG-1 cells displayed
      only barely detectable amounts of c-jun transcripts when cultured in the presence
      of serum, Ara-C at concentrations of 1 to 50 microM induced c-jun transcripts in
      a dose-dependent fashion. Time course studies showed that 10 microM Ara-C induced
      c-jun transcripts 6 hr after initiation of culture. Induction of c-jun mRNA was
      independent of de novo protein synthesis, because the protein synthesis inhibitor
      cycloheximide failed to alter Ara-C-induced c-jun mRNA accumulation. Furthermore,
      cycloheximide did not induce c-jun transcripts, ruling out the possibility of
      posttranscriptional stabilization of c-jun mRNA by labile proteins, as has been
      previously reported for a variety of serum-inducible protooncogenes and early
      response genes. Moreover, nuclear run-on analysis disclosed that c-jun induction
      by Ara-C in KG-1 cells took place at a transcriptional level. Taken together,
      these findings indicate that c-jun mRNA, unlike its rapid (within minutes)
      induction by serum in fibroblasts, is induced by Ara-C in KG-1 cells following a
      much more prolonged time course and is regulated essentially at a transcriptional
      level.

PMID- 1996083
TI  - Monomorphic and polymorphic human arylamine N-acetyltransferases: a comparison of
      liver isozymes and expressed products of two cloned genes.
AB  - A genetic polymorphism of human liver arylamine N-acetyltransferase (NAT; EC
      2.3.1.5) enzyme activity divides populations into distinguishable "slow
      acetylator" and "rapid acetylator" phenotypes. Two human genes, NAT1 and NAT2,
      encoding NAT proteins [DNA Cell Biol. 9:193-203 (1990)] were transiently
      expressed in cultured monkey kidney COS-1 cells, and the resulting recombinant
      NAT1 and NAT2 proteins were compared with N-acetyltransferase activities in human
      liver cytosol with respect to their stability, chromatographic behavior on anion
      exchange columns, electrophoretic mobility, and arylamine acceptor substrate
      specificity. NAT1 was far less stable in vitro than NAT2. Under conditions
      designed to optimize enzyme stability, anion exchange chromatography experiments
      revealed that enzymes corresponding to both recombinant NAT1 and NAT2 were
      expressed in human liver. Recombinant and human liver NAT1 enzymes showed the
      same characteristic selectivity (low apparent Km, high Vmax) for the
      "monomorphic" substrates p-aminosalicylic acid and p-aminobenzoic acid. Such
      substrates fail to discriminate between the acetylator phenotypes in vivo. The
      same criteria established that recombinant NAT2 was indistinguishable from one of
      two previously observed N-acetyltransferases (NAT2A and NAT2B) whose liver
      contents correlate with acetylator phenotype in human populations. Recombinant
      NAT2 and the liver NAT2 isoforms NAT2A and NAT2B selectivity N-acetylated the
      "polymorphic" substrates sulfamethazine and procainamide, whose disposition in
      vivo is affected by the acetylation polymorphism. Interestingly, the carcinogen 2
      aminofluorene was very efficiently metabolized by both NAT1 and NAT2. Independent
      regulation of NAT1 and NAT2 genes was suggested by a lack of correlation of NAT1
      and NAT2 enzyme activities in cytosols from 39 human livers. The results provide
      strong evidence that the NAT2 locus is the site of the human acetylation
      polymorphism. In addition, the use of recombinant NAT1 and NAT2 will allow us to
      predict whether any given arylamine will be polymorphically acetylated in humans.

PMID- 1996084
TI  - Catabolism of 3'-azido-3'-deoxythymidine in hepatocytes and liver microsomes,
      with evidence of formation of 3'-amino-3'-deoxythymidine, a highly toxic
      catabolite for human bone marrow cells.
AB  - Metabolic studies in humans have demonstrated that 3'-azido-3'-deoxythymidine
      (AZT) is primarily eliminated as its 5'-O-glucuronide (GAZT). However, no
      detailed cellular metabolic studies have been reported on the complete catabolic
      fate of AZT at the hepatic site. Because the liver is probably the major site of
      AZT catabolism, the metabolism and transmembrane distribution of AZT were
      evaluated in freshly isolated rat hepatocytes, a model for the study at the
      cellular level of biosynthetic, catabolic, and transport phenomena in the liver.
      Following exposure of cells to 10 microM [3H]AZT, the predominant intracellular
      catabolite was GAZT, which reached a concentration of approximately 22 microM by
      60 min. Additionally, under nonreducing conditions substantial levels of two
      previously unidentified AZT catabolites that were formed at the hepatic site and
      were distinct from any known anabolites or catabolites were also detected. These
      catabolites were identified as 3'-amino-3'-deoxythymidine (AMT) by fast atom
      bombardment mass spectrometry and 3'-amino-3'-deoxythymidine glucuronide (GAMT)
      through specific enzymatic hydrolysis. However, AMT was not a substrate for
      uridine 5'-diphosphoglucuronyltransferase and GAMT was found to be a reductive
      product of GAZT. Studies using rat and human liver microsomes demonstrated that
      the rate of formation of AMT and GAMT increased in the presence of NADPH,
      suggesting the involvement of a NADPH-dependent enzyme system. Studies using
      human hematopoietic progenitor cells demonstrated that AMT was 5- to 7-fold more
      toxic to human colony-forming units granulocyte-macrophage and burst-forming
      units erythroid than was AZT. This study provides the first detailed catabolic
      profile of AZT at the hepatic site and emphasizes the critical role that the
      liver plays in drug clearance. Formation of AMT, a highly toxic catabolite of
      AZT, raises a question regarding the role of AMT in the cytotoxic effects of AZT
      observed in patients.

PMID- 1996085
TI  - Transforming growth factor beta 1 inhibition of p34cdc2 phosphorylation and
      histone H1 kinase activity is associated with G1/S-phase growth arrest.
AB  - Transforming growth factor beta 1 (TGF beta 1) is a potent inhibitor of
      epithelial cell proliferation. We present data which indicate that epithelial
      cell proliferation is inhibited when TGF beta 1 is added throughout the
      prereplicative G1 phase. Cultures become reversibly blocked in late G1 at the
      G1/S-phase boundary. The inhibitory effects of TGF beta 1 on cell growth occur in
      the presence of the RNA synthesis inhibitor 5,6-dichloro-1-beta-D
      ribofuranosylbenzimidazole. Associated with this inhibitory effect is a decrease
      in the phosphorylation and histone H1 kinase activity of the p34cdc2 protein
      kinase. These data suggest that TGF beta 1 growth inhibition in epithelial cells
      involves the regulation of p34cdc2 activity at the G1/S transition.

PMID- 1996086
TI  - Role of the mammalian transcription factors IIF, IIS, and IIX during elongation
      by RNA polymerase II.
AB  - We have used a recently developed system that allows the isolation of complexes
      competent for RNA polymerase II elongation (E. Bengal, A. Goldring, and Y. Aloni,
      J. Biol. Chem. 264:18926-18932, 1989). Pulse-labeled transcription complexes were
      formed at the adenovirus major late promoter with use of HeLa cell extracts.
      Elongation-competent complexes were purified from most of the proteins present in
      the extract, as well as from loosely bound elongation factors, by high-salt gel
      filtration chromatography. We found that under these conditions the nascent RNA
      was displaced from the DNA during elongation. These column-purified complexes
      were used to analyze the activities of different transcription factors during
      elongation by RNA polymerase II. We found that transcription factor IIS (TFIIS),
      TFIIF, and TFIIX affected the efficiency of elongation through the adenovirus
      major late promoter attenuation site and a synthetic attenuation site composed of
      eight T residues. These factors have distinct activities that depend on whether
      they are added before RNA polymerase has reached the attenuation site or at the
      time when the polymerase is pausing at the attenuation site. TFIIS was found to
      have antiattenuation activity, while TFIIF and TFIIX stimulated the rate of
      elongation. In comparison with TFIIF, TFIIS is loosely bound to the elongation
      complex. We also found that the activities of the factors are dependent on the
      nature of the attenuator. These results indicate that at least three factors play
      a major role during elongation by RNA polymerase II.

PMID- 1996087
TI  - A stem cell-specific silencer in the primer-binding site of a retrovirus.
AB  - Retrovirus expression in embryonal carcinoma (EC) cells is blocked at a
      postintegration stage of the viral life cycle, in part because of the inadequate
      function of the viral long terminal repeat promoter in this cell type. However,
      selection for retrovirus expression in EC cells has identified mutations in
      Moloney murine leukemia virus (M-MuLV) located in the tRNA primer-binding site
      (PBS) region which relieve the EC cell-specific repression. We have found that
      exchanging the M-MuLV proline PBS for a glutamine one in a recombinant virus
      permits expression in EC cells. By using the recombinant virus as a backbone, the
      EC cell-specific repressor-binding site (RBS) element has been mapped to M-MuLV
      nucleotides 147 to 174. The RBS does not require precise positioning downstream
      of the M-MuLV promoter and can function in either orientation and in an intron,
      indicating that the regulatory effect is probably at the DNA, rather than RNA,
      level. We also show that the RBS element can repress heterologous promoters from
      an upstream position. Our results indicate that the RBS acts as a silencer that
      its inhibitory effect is mediated by a trans-acting factor, and that the
      mechanism of action is probably at the level of transcription. Through in vitro
      binding assays we have identified a binding factor which specifically recognizes
      the wild-type RBS sequence (binding factor A). The binding characteristics of
      factor A suggest that it is a stem cell repressor which acts at the M-MuLV RBS.
      Our DNA-binding assays also have identified a unique binding factor (binding
      factor Hp) which specifically recognizes a hemimethylated form of the wild-type
      RBS. This factor may play a role in methylation mediated control of retrovirus
      expression in EC cells.

PMID- 1996088
TI  - A unique pathway of double-strand break repair operates in tandemly repeated
      genes.
AB  - The RAD52 gene product of the yeast Saccharomyces cerevisiae is required for most
      spontaneous recombination and almost all double-strand break (DSB) repair. In
      contrast to recombination elsewhere in the genome, recombination in the ribosomal
      DNA (rDNA) array is RAD52 independent. To determine the fate of a DSB in the rDNA
      gene array, a cut site for the HO endonuclease was inserted into the rDNA in a
      strain containing an inducible HO gene. DSBs were efficiently repaired at this
      site, even in the absence of the RAD52 gene product. Efficient RAD52-independent
      DSB repair was also observed at another tandem gene array, CUP1, consisting of 18
      repeat units. However, in a smaller CUP1 array, consisting of only three units,
      most DSBs (ca. 80%) were not repaired and resulted in cell death. All RAD52
      independent DSB repair events examined resulted in the loss of one or more repeat
      units. We propose a model for DSB repair in repeated sequences involving the
      generation of single-stranded tails followed by reannealing.

PMID- 1996089
TI  - Heat shock transcription factor activates transcription of the yeast
      metallothionein gene.
AB  - In the yeast Saccharomyces cerevisiae, transcription of the metallothionein gene
      CUP1 is induced by copper and silver. Strains with a complete deletion of the
      ACE1 gene, the copper-dependent activator of CUP1 transcription, are
      hypersensitive to copper. These strains have a low but significant basal level of
      CUP1 transcription. To identify genes which mediate basal transcription of CUP1
      or which activate CUP1 in response to other stimuli, we isolated an extragenic
      suppressor of an ace1 deletion. We demonstrate that a single amino acid
      substitution in the heat shock transcription factor (HSF) DNA-binding domain
      dramatically enhances CUP1 transcription while reducing transcription of the SSA3
      gene, a member of the yeast hsp70 gene family. These results indicate that yeast
      metallothionein transcription is under HSF control and that metallothionein
      biosynthesis is important in response to heat shock stress. Furthermore, our
      results suggest that HSF may modulate the magnitude of individual heat shock gene
      transcription by subtle differences in its interaction with heat shock elements
      and that a single-amino-acid change can dramatically alter the activity of the
      factor for different target genes.

PMID- 1996090
TI  - CAP is a bifunctional component of the Saccharomyces cerevisiae adenylyl cyclase
      complex.
AB  - CAP, a protein from Saccharomyces cerevisiae that copurifies with adenylyl
      cyclase, appears to be required for yeast cells to be fully responsive to RAS
      proteins. CAP also appears to be required for normal cell morphology and
      responsiveness to nutrient deprivation and excess. We describe here a molecular
      and phenotypic analysis of the CAP protein. The N-terminal domain is necessary
      and sufficient for cellular response to activated RAS protein, while the C
      terminal domain is necessary and sufficient for normal cellular morphology and
      responses to nutrient extremes. Thus, CAP is a novel example of a bifunctional
      component involved in the regulation of diverse signal transduction pathways.

PMID- 1996091
TI  - The bidirectional promoter of the divergently transcribed mouse Surf-1 and Surf-2
      genes.
AB  - The ubiquitously expressed mouse Surf-1 and Surf-2 genes are divergently
      transcribed, and their heterogeneous start sites are separated by up to a maximum
      of only 73 bp. By using in vitro DNase I, dimethyl sulfate methylation, and gel
      retardation assays, we have identified five putative promoter control elements
      between and around the Surf-1 and Surf-2 start sites. The effects of each site on
      the regulation of Surf-1 and Surf-2 transcription have been studied in vivo, and
      four sites were found to be functional promoter elements. A novel binding site is
      required for efficient use of the intermediate but not the major start site of
      Surf-1. Three elements function in a bidirectional manner and are shared for
      efficient and accurate expression of both Surf-1 and Surf-2. One is an UEF (USF,
      MLTF) binding site which had a small effect on the use of the intermediate start
      sites of Surf-1 and also affected the major start sites of Surf-2. Another has
      sequence homology to the RPG alpha binding site associated with some ribosomal
      protein gene promoters and is required for efficient expression of the major but
      not intermediate start sites of Surf-1 and all start sites of Surf-2. The third,
      an RPG alpha-like site, is used for all start sites of both Surf-1 and Surf-2.
      Dissection of this cellular promoter region showed that different binding sites
      affect the use of different start sites and revealed a complex interaction
      between multiple elements that constitute a bona fide bidirectional promoter.

PMID- 1996092
TI  - Use of a screen for synthetic lethal and multicopy suppressee mutants to identify
      two new genes involved in morphogenesis in Saccharomyces cerevisiae.
AB  - Genes CDC24 and CDC42 are required for the establishment of cell polarity and for
      bud formation in Saccharomyces cerevisiae. Temperature-sensitive (Ts-) mutations
      in either of these genes cause arrest as large, unbudded cells in which the
      nuclear cycle continues. MSB1 was identified previously as a multicopy suppressor
      of Ts- cdc24 and cdc42 mutations. We have now sequenced MSB1 and constructed a
      deletion of this gene. The predicted amino acid sequence does not closely
      resemble any other in the available data bases, and the deletion does not produce
      any readily detectable phenotype. However, we have used a colony-sectoring assay
      to identify additional genes that appear to interact with MSB1 and play a role in
      bud emergence. Starting with a strain deleted for the chromosomal copy of MSB1
      but containing MSB1 on a high-copy-number plasmid, mutants were identified in
      which MSB1 had become essential for viability. The new mutations defined two
      genes, BEM1 and BEM2; both the bem1 and bem2 mutations are temperature sensitive
      and are only partially suppressed by MSB1. In bem1 cells, a single copy of MSB1
      is necessary and sufficient for viability at 23 or 30 degrees C, but even
      multiple copies of MSB1 do not fully suppress the growth defect at 37 degrees C.
      In bem2 cells, a single copy of MSB1 is necessary and sufficient for viability at
      23 degrees C, multiple copies are necessary for viability at 30 degrees C, and
      even multiple copies of MSB1 do not suppress the growth defect at 37 degrees C.
      In a wild-type background (i.e., a single chromosomal copy of MSB1), both bem1
      and bem2 mutations cause cells to become large and multinucleate even during
      growth at 23 degrees C, suggesting that these genes are involved in bud
      emergence. This suggestion is supported for BEM1 by other evidence obtained in a
      parallel study (J. Chant, K. Corrado, J. Pringle, and I. Herskowitz, submitted
      for publication). BEM1 maps centromere distal to TYR1 on chromosome II, and BEM2
      maps between SPT15 and STP2 on chromosome V.

PMID- 1996093
TI  - Molecular cloning and characterization of a novel glycoprotein, gp34, that is
      specifically induced by the human T-cell leukemia virus type I transactivator
      p40tax.
AB  - We have cloned and sequenced a cDNA encoding gp34, a novel glycoprotein expressed
      in cells bearing human T-cell leukemia virus type I (HTLV-I). HTLV-I has a trans
      acting transcriptional activator, p40tax, that is thought to be implicated in
      leukemogenesis through the activation of cellular enhancers. With a subline (JPX
      9) of the human T-cell line Jurkat, in which p40tax is inducible, gp34 was shown
      to be of cellular origin and to be transcriptionally activated by p40tax. It was
      also demonstrated that two species of mRNA are generated from one copy of the
      gp34 gene and that these mRNAs encode the identical gp34 product and differ in
      the 3' untranslated region. Analysis of the deduced amino acid sequence of gp34
      showed that it lacks typical signal peptides; however, it has a hydrophobic
      stretch for membrane anchoring and four possible N-linked glycosylation sites at
      the carboxy-terminal portion, indicating that it belongs to the family of
      membrane proteins whose carboxy-terminal portion protrudes out of the cell. The
      gp34 gene displayed relatively delayed induction compared with other genes
      activated by p40tax. Taken together with the observation of the dependence of
      gp34 expression on HTLV-I p40tax, unlike other p40tax-dependent genes such as
      those for the interleukin-2 receptor alpha chain and c-fos, which are expressed
      or induced under physiological conditions, we predict that the mechanism involved
      in the induction of gp34 expression by p40tax is distinct from and more intricate
      than those for the previously characterized genes.

PMID- 1996094
TI  - p68 RNA helicase: identification of a nucleolar form and cloning of related genes
      containing a conserved intron in yeasts.
AB  - The human p68 protein is an RNA-dependent ATPase and RNA helicase which was first
      identified because of its immunological cross-reaction with a viral RNA helicase,
      simian virus 40 large T antigen. It belongs to a recently discovered family of
      proteins (DEAD box proteins) that share extensive regions of amino acid sequence
      homology, are ubiquitous in living organisms, and are involved in many aspects of
      RNA metabolism, including splicing, translation, and ribosome assembly. We have
      shown by immunofluorescent microscopy that mammalian p68, which is excluded from
      the nucleoli during interphase, translocates to prenucleolar bodies during
      telophase. We have cloned 55% identical genes from both Schizosaccharomyces pombe
      and Saccharomyces cerevisiae and shown that they are essential in both yeasts.
      The human and yeast genes contain a large intron whose position has been
      precisely conserved. In S. cerevisiae, the intron is unusual both because of its
      size and because of its location near the 3' end of the gene. We discuss possible
      functional roles for such an unusual intron in an RNA helicase gene.

PMID- 1996095
TI  - Dissection of the mouse N-ras gene upstream regulatory sequences and
      identification of the promoter and a negative regulatory element.
AB  - The 5' flanking region of the mouse N-ras gene was investigated to determine the
      elements governing transcriptional activity of the gene. The promoter did not
      contain typical TATA or CCAAT boxes, and according to primer extension and RNase
      protection analyses, transcription started at several sites. These assays also
      confirmed the short nucleotide distance interposed between the N-ras
      transcription unit and the previously described upstream unr gene. Chromatin
      studies performed by digestion of nuclei with DNase I revealed the presence of
      four hypersensitive sites: a, b, c, and d. Deletion mutagenesis of the 5'
      flanking region revealed sequences responsible for both promotion and inhibition
      of transcription. These sequences resided within 230 bp upstream of the
      transcription initiation site. Hypersensitive site b colocalized with the 76-bp
      segment with promoter activity. The negative regulatory element at position -180
      colocalized with hypersensitive site a, was active on the N-ras promoter in
      stable as well as transient assays, and down-regulated the heterologous herpes
      simplex virus thymidine kinase promoter. Footprint analysis and in vivo
      transfection-competition experiments indicated that a trans-acting factor is
      responsible for the negative effect on transcription. The interaction between the
      cis-acting negative regulatory element and the promoter region may play a role in
      the tissue- and developmental-stage-specific patterns of expression of the N-ras
      gene.

PMID- 1996096
TI  - Mutant p53 tumor suppressor alleles release ras-induced cell cycle growth arrest.
AB  - Overexpression of an activated ras gene in the rat embryo fibroblast line REF52
      results in growth arrest at either the G1/S or G2/M boundary of the cell cycle.
      Both the DNA tumor virus proteins simian virus 40 large T antigen and adenovirus
      5 E1a are able to rescue ras induced lethality and cooperate with ras to fully
      transform REF52 cells. In this report, we present evidence that the wild-type
      activity of the tumor suppressor gene p53 is involved in the negative growth
      regulation of this model system. p53 genes encoding either a p53Val-135 or p53Pro
      193 mutation express a highly stable p53 protein with a conformation-dependent
      loss of wild-type activity and the ability to eliminate any endogenous wild-type
      p53 activity in a dominant negative manner. In cotransfection assays, these
      mutant p53 genes are able to rescue REF52 cells from ras-induced growth arrest,
      resulting in established cell lines which express elevated levels of the ras
      oncoprotein and show morphological transformation. Full transformation, as
      assayed by tumor formation in nude mice, is found only in the p53Pro-193-plus-ras
      transfectants. These cells express higher levels of the ras protein than do the
      p53Val-135-plus-ras-transfected cells. Transfection of REF52 cells with ras alone
      or a full-length genomic wild-type p53 plus ras results in growth arrest and
      lethality. Therefore, the selective event for p53 inactivation or loss during
      tumor progression may be to overcome a cell cycle restriction induced by oncogene
      overexpression (ras). These results suggest that a normal function of p53 may be
      to mediate negative growth regulation in response to ras or other proliferative
      inducing signals.

PMID- 1996097
TI  - The ubiquitous transcription factor Oct-1 and the liver-specific factor HNF-1 are
      both required to activate transcription of a hepatitis B virus promoter.
AB  - The liver-specific transcription factor HNF-1 activates transcription of several
      mammalian hepatocyte-specific genes. The hepatitis B virus preS1 promoter shows
      hepatocyte specificity, which has been ascribed to binding of HNF-1 to a cognate
      DNA sequence upstream of the TATA box. We show here that there is an adjacent
      site that binds the ubiquitous transcription factor Oct-1. Both the Oct-1 and HNF
      1 sites are necessary for liver-specific transcription of the preS1 promoter, but
      neither site alone activates transcription. The Oct-1 site is also necessary for
      activation of the preS1 promoter in HeLa cells, expressing transfected HNF-1. Our
      results show that while Oct-1 is not restricted to hepatocytes, it nevertheless
      can play a critical role in the expression of a liver-specific gene.

PMID- 1996098
TI  - Episome-generated N-myc antisense RNA restricts the differentiation potential of
      primitive neuroectodermal cell lines.
AB  - Neuroectodermal tumors of childhood provide a unique opportunity to examine the
      role of genes potentially regulating neuronal growth and differentiation because
      many cell lines derived from these tumors are composed of at least two distinct
      morphologic cell types. These types display variant phenotypic characteristics
      and spontaneously interconvert, or transdifferentiate, in vitro. The factors that
      regulate transdifferentiation are unknown. Application of antisense approaches to
      the transdifferentiation process has allowed us to explore the precise role that
      N-myc may play in regulating developing systems. We now report construction of an
      episomally replicating expression vector designed to generate RNA antisense to
      part of the human N-myc gene. Such a vector is able to specifically inhibit N-myc
      expression in cell lines carrying both normal and amplified N-myc alleles.
      Inhibition of N-myc expression blocks transdifferentiation in these lines, with
      accumulation of cells of an intermediate phenotype. A concomitant decrease in
      growth rate but not loss of tumorigenicity was observed in the N-myc nonamplified
      cell line CHP-100. Vector-generated antisense RNA should allow identification of
      genes specifically regulated by the proto-oncogene N-myc.

PMID- 1996099
TI  - Prohibitin, an evolutionarily conserved intracellular protein that blocks DNA
      synthesis in normal fibroblasts and HeLa cells.
AB  - Genes that act inside the cell to negatively regulate proliferation are of great
      interest because of their implications for such processes as development and
      cancer, but these genes have been difficult to clone. This report details the
      cloning and analysis of cDNA for prohibitin, a novel mammalian antiproliferative
      protein. Microinjection of synthetic prohibitin mRNA blocks entry into S phase in
      both normal fibroblasts and HeLa cells. Microinjection of an antisense
      oligonucleotide stimulates entry into S phase. By sequence comparison, the
      prohibitin gene appears to be the mammalian analog of Cc, a Drosophila gene that
      is vital for normal development.

PMID- 1996101
TI  - Testing an "in-out" targeting procedure for making subtle genomic modifications
      in mouse embryonic stem cells.
AB  - We have introduced a 4-bp insertion into the hypoxanthine
      phosphoribosyltransferase (HPRT) gene of a mouse embryonic stem (ES) cell line by
      using an "in-out" targeting procedure. During the in step, a homologous
      integration reaction, we targeted a correcting plasmid to a partially deleted
      hprt- locus by using an integrating vector that carried a 4-bp insertion in the
      region of DNA homologous to the target locus. HPRT+ recombinants were isolated by
      direct selection in hypoxanthine-aminopterin-thymidine (HAT) medium. The HATr
      cell lines were then grown in medium containing 6-thioguanine (6-TG) to select
      for hprt- revertants resulting from the excision of the integrated vector
      sequences. The revertants were examined by Southern blot hybridization to
      determine the accuracy of this out reaction and the frequency of retaining the 4
      bp modification in the genome. Of the 6-TGr colonies examined, 88% had accurately
      excised the integrated vector sequences; 19 of 20 accurate revertants retained
      the 4-bp insertion in the resulting hprt- gene. We suggest a scheme for making
      the in-out targeting procedure generally useful to modify the mammalian genome.

PMID- 1996100
TI  - Sequences far downstream from the classical tRNA promoter elements bind RNA
      polymerase III transcription factors.
AB  - We have examined the interaction of transcription factors TFIIIC and TFIIID with
      a silkworm alanine tRNA gene. Previous functional analysis showed that the
      promoter for this gene is unusually large compared with the classical tRNA
      promoter elements (the A and B boxes) and includes sequences downstream from the
      transcription termination site. The goal of the experiments reported here was to
      determine which sequences within the full promoter make stable contacts with
      transcription factors. We show that when TFIIIC and TFIIID are combined, a
      complex is formed with the tRNA(Ala)C gene. Neither factor alone can form this
      complex. DNase I digestion of gene-factor complexes reveals that most of the
      tRNA(Ala)C promoter is in contact with factors. The protected region extends from
      -1 to at least +136 and includes both the A and B boxes and the previously
      identified downstream promoter sequences. Analysis of mutant promoters shows that
      sequence-specific contacts throughout the protected region are required for
      binding. The role of 3'-flanking sequences in transcription factor binding
      explains the contribution of these sequences to the tRNA(Ala)C promoter. We
      discuss the possibility that such sequences affect promoter strength in other
      tRNA genes.

PMID- 1996102
TI  - A transferrinlike (hemiferrin) mRNA is expressed in the germ cells of rat testis.
AB  - In the testis, germ cells which are separated from the serum by the blood-testis
      barrier rely primarily on the Sertoli cell to obtain nutrients. For example,
      transferrin synthesized by the Sertoli cell is important in delivering iron from
      the serum to the developing germ cells. Because of its role in the testis,
      Sertoli cell transferrin protein and mRNA have been extensively studied. By using
      RNA blot analysis of rat testicular tissue, we detected a transcript of 2.6 kb
      which is attributed to transferrin. In addition, we detected a novel mRNA of 0.9
      kb which had sequence similarity to the 3' end of transferrin. This 0.9-kb mRNA
      was present in germ cells, but not Sertoli cells, liver, or brain. The primary
      source of this mRNA in the testis was round spermatids. Sequence analysis of a
      cDNA clone showed that this mRNA encoded a protein with sequence similarity to
      the carboxy terminus of transferrin. Polysome analysis indicated that this
      transcript was translated and may therefore have importance in the iron
      metabolism of germ cells. The evolutionary implications between the
      transferrinlike mRNA germ cells and the gene duplication event which resulted in
      the diferric binding of transferrin are discussed.

PMID- 1996103
TI  - Replication initiates at multiple locations on an autonomously replicating
      plasmid in human cells.
AB  - We have used a two-dimensional gel electrophoresis mapping technique to determine
      where DNA replication initiates on a plasmid which utilizes a fragment of human
      DNA to replicate autonomously in human cells. Replication was found to initiate
      at multiple locations on the plasmid carrying the human sequence, in contrast to
      the pattern seen for an Epstein-Barr virus vector which served as a control with
      a fixed origin. The family of repeats, a portion of the Epstein-Barr virus origin
      of replication which is present our plasmid, was shown to function as a
      replication fork barrier. The nature of the stalled replicative intermediates on
      the human DNA-based plasmid further indicated that replication did not initiate
      at a single fixed position each time the plasmid replicated. The results suggest
      that the replication apparatus used to duplicate DNA in human cells may not have
      precise sequence requirements which target initiation to specific locations.

PMID- 1996104
TI  - A similar gene is shared by both the variant surface glycoprotein and procyclin
      gene transcription units of Trypanosoma brucei.
AB  - The genes for the variant surface glycoprotein (VSG) and procyclin are expressed
      in a mutually exclusive manner during the life cycle of Trypanosoma brucei and
      synthesize the most abundant mRNAs specific to the bloodstream and procyclic
      stages of the parasite, respectively. Genes belonging to the polycistronic
      transcription unit of the VSG gene (expression site-associated genes [ESAGs]) are
      uniquely expressed in the bloodstream form, but some members of ESAG families
      (genes related to ESAGs [GRESAGs]) are independently transcribed outside the VSG
      gene expression site. We report here that a gene related to ESAG 2, GRESAG 2.1,
      is present and expressed in a procyclin gene transcription unit (PARP A locus),
      which is polycistronic. Members of the ESAG 2 family are thus present in the two
      major differentially stage-regulated transcription units of this parasite.

PMID- 1996105
TI  - An "attenuator domain" is sandwiched by two distinct transactivation domains in
      the transcription factor C/EBP.
AB  - C/EBP is a rat liver DNA-binding protein which can act as a transcription factor.
      Its N-terminal portion contains three distinct domains. The first domain (amino
      acids 1 to 107) appears to be a highly potent transactivator. The second domain
      (amino acids 107 to 170) does not appear to exhibit either activation or
      repression activity. This domain is defined as an "attenuator domain" because its
      presence under four different sequence contexts reproducibly decreases the effect
      of transactivation of C/EBP. The third domain (amino acids 171 to 245) is a
      relatively weaker transactivator with a striking proline-rich motif. Deletional
      analysis of this third domain has shown that a 45-amino-acid region is sufficient
      for transactivation. This region (amino acids 171 to 215) contains 12 proline, 6
      histidine, and mainly hydrophobic or noncharged amino acids. Further mutational
      analysis of a highly conserved proline-octamer region within this domain
      indicates that a specific proline content is not crucial for transactivation.

PMID- 1996107
TI  - Interaction of a lens cell transcription factor with the proximal domain of the
      mouse gamma F-crystallin promoter.
AB  - The elements regulating lens-specific expression of the mouse gamma F-crystallin
      gene were examined. Here we show that mouse gamma F-crystallin sequences -67 to
      +45 contain a low basal level of lens-specific promoter activity and that
      sequences -67 to -25, which are highly conserved among different gamma-crystallin
      genes, are able to function as a strong transcriptional activator when duplicated
      and placed upstream of the TATA box. We also show that nuclear factors from lens
      and nonlens cells are able to form different complexes with sequences centered at
      -46 to -36 and demonstrate that binding of the factor from lens cells correlates
      with lens-specific promoter activity of the mouse gamma F-crystallin gene.

PMID- 1996108
TI  - Extinction of insulin gene expression in hybrids between beta cells and
      fibroblasts is accompanied by loss of the putative beta-cell-specific
      transcription factor IEF1.
AB  - Insulin-producing cells and fibroblasts were fused to produce hybrid lines. In
      hybrids derived from both hamster and rat insulinoma cells, no insulin mRNA could
      be detected in any of seven lines examined by Northern (RNA) analysis despite the
      presence in each line of the insulin genes of both parental cells. Hybrid cells
      were transfected with recombinant chloramphenicol acetyltransferase plasmids
      containing defined segments of the rat insulin I gene 5' flank. We observed no
      transcriptional activity of the intact insulin enhancer or of IEB2, a critical
      cis-acting element of the insulin enhancer. IEB2 has previously been shown to
      interact in vitro with IEF1, a DNA-binding activity observed selectively in
      insulin-producing cells. Hybrid cells showed no detectable IEF1 activity.
      Furthermore, the insulin enhancer was unable to reduce transcription directed by
      the Moloney sarcoma virus enhancer in a double-enhancer construct. Thus,
      extinction of insulin gene expression in the hybrids apparently does not operate
      through a direct action of repressors on the insulin enhancer; rather, extinction
      is accompanied by, and may be caused by, reduced DNA-binding activity of the
      putative transcriptional activator IEF1.

PMID- 1996106
TI  - Chicken beta B1-crystallin gene expression: presence of conserved functional
      polyomavirus enhancer-like and octamer binding-like promoter elements found in
      non-lens genes.
AB  - Expression of the chicken beta B1-crystallin gene was examined. Northern (RNA)
      blot and primer extension analyses showed that while abundant in the lens, the
      beta B1 mRNA is absent from the liver, brain, heart, skeletal muscle, and
      fibroblasts of the chicken embryo, suggesting lens specificity. Promoter
      fragments ranging from 434 to 126 bp of 5'-flanking sequence (plus 30 bp of exon
      1) of the beta B1 gene fused to the bacterial chloramphenicol acetyltransferase
      gene functioned much more efficiently in transfected embryonic chicken lens
      epithelial cells than in transfected primary muscle fibroblasts or HeLa cells.
      Transient expression of recombinant plasmids in cultured lens cells, DNase I
      footprinting, in vitro transcription in a HeLa cell extract, and gel mobility
      shift assays were used to identify putative functional promoter elements of the
      beta B1-crystallin gene. Sequence analysis revealed a number of potential
      regulatory elements between positions -126 and -53 of the beta B1 promoter,
      including two Sp1 sites, two octamer binding sequence-like sites (OL-1 and OL-2),
      and two polyomavirus enhancer-like sites (PL-1 and PL-2). Deletion and site
      specific mutation experiments established the functional importance of PL-1 (-116
      to -102), PL-2 (-90 to -76), and OL-2 (-75 to -68). DNase I footprinting using a
      lens or a HeLa cell nuclear extract and gel mobility shifts using a lens nuclear
      extract indicated the presence of putative lens transcription factors binding to
      these DNA sequences. Competition experiments provided evidence that PL-1 and PL-2
      recognize the same or very similar factors, while OL-2 recognizes a different
      factor. Our data suggest that the same or closely related transcription factors
      found in many tissues are used for expression of the chicken beta B1-crystallin
      gene in the lens.

PMID- 1996109
TI  - Two monomers of yeast transcription factor ADR1 bind a palindromic sequence
      symmetrically to activate ADH2 expression.
AB  - ADR1 is a transcription factor from Saccharomyces cerevisiae that regulates ADH2
      expression through a 22-bp palindromic sequence (UAS1). Size fractionation
      studies revealed that full-length ADR1 and a truncated ADR1 protein containing
      the first 229 amino acids, which has the complete DNA-binding domain, ADR1:17
      229, exist as monomers in solution. However, two complexes were formed with
      target DNA-binding sites. UV-cross-linking studies suggested that these two
      complexes represent one and two molecules of ADR1 bound to DNA. Studies of ADR1
      complexes formed with wild-type UAS1, asymmetrically altered UAS1, and one half
      of UAS1 showed that ADR1 can bind to one half of UAS1 and gives rise to a complex
      containing one molecule of ADR1. Dimethyl sulfate interference studies were
      consistent with this interpretation and in addition indicated that purine contact
      sites in each half of UAS1 were identical. Increasing the distance between the
      two halves of UAS1 had at most a minor effect of the thermodynamics of formation
      of the two complexes. These data are more consistent with ADR1 binding as two
      independent monomers, one to each half of UAS1. However, binding of two ADR1
      monomers at UAS1 is apparently essential for transactivation in vivo. Further, we
      have identified a stretch of 18 amino acid residues amino terminal to the zinc
      two-finger domains of ADR1 which is essential for DNA-binding activity. Single
      amino acid substitutions of residues in this region resulted in severely reduced
      DNA-binding activity.

PMID- 1996110
TI  - Interleukin-7 retroviruses transform pre-B cells by an autocrine mechanism not
      evident in Abelson murine.
AB  - In this study, we have constructed retroviral vectors expressing the interleukin
      7 (IL-7) cDNA and have used infection with these retroviruses to express this
      cytokine endogenously in an IL-7-dependent pre-B-cell line. Infection with IL-7
      retroviruses, but not with a control retrovirus, resulted in the conversion of
      the cells to IL-7 independence. The frequency at which this occurred, together
      with data on vector expression levels, indicated that secondary events were
      required for factor independence in this system. Southern analysis showed that
      the IL-7-dependent clones harbored unrearranged copies of the vector proviruses.
      The factor-independent cells produced variable quantities of IL-7 as measured by
      an IL-7-specific bioassay, and their proliferation could be substantially
      inhibited by a neutralizing antibody directed against IL-7, indicating that a
      classical autocrine-mechanism was responsible for their transformation. These IL
      7-independent cells were tumorigenic, in contrast to the parental IL-7-dependent
      cells or those infected with a control vector. These results showed that IL-7
      could participate in the malignant transformation of pre-B cells. However,
      neither of two Abelson murine leukemia virus (A-MuLV)-transformed pre-B-cell
      lines expressed detectable IL-7 mRNA, at a level of sensitivity corresponding to
      less than one molecule of mRNA per cell. Moreover, the proliferation of the A
      MuLV transformants was unaffected by addition of the IL-7 antisera under
      conditions in which parallel experiments with IL-7 virus-infected cells resulted
      in greater than 70% growth inhibition. Thus, transformation of pre-B cells by A
      MuLV was not associated with a demonstrable autocrine loop of IL-7 synthesis.
      These results show that IL-7 can participate in the malignant transformation of
      pre-B cells and suggest studies aimed at assessing the role of autocrine
      production of IL-7 in the generation of human leukemias and lymphomas.

PMID- 1996111
TI  - Involvement of long terminal repeat U3 sequences overlapping the transcription
      control region in human immunodeficiency virus type 1 mRNA 3' end formation.
AB  - In retroviral proviruses, the poly(A) site is present in both long terminal
      repeats (LTRs) but used only in the 3' position. One mechanism to account for
      this selective poly(A) site usage is that LTR U3 sequences, transcribed only from
      the 3' poly(A) site, are required in the RNA for efficient processing. To test
      this possibility, mutations were made in the human immunodeficiency virus type 1
      (HIV-1) U3 region and the mutated LTRs were inserted into simple and complex
      transcription units. HIV-1 poly(A) site usage was then quantitated by S1 nuclease
      analysis following transfection of each construct into human 293 cells. The
      results showed that U3 sequences confined to the transcription control region
      were required for efficient usage of the HIV-1 poly(A) site, even when it was
      placed 1.5 kb from the promoter. Although the roles of U3 in processing and
      transcription activation were separable, optimal 3' end formation was partly
      dependent on HIV-1 enhancer and SP1 binding site sequences.

PMID- 1996112
TI  - Replication-competent human mitochondrial DNA lacking the heavy-strand promoter
      region.
AB  - We identified two patients with progressive external ophthalmoplegia, a
      mitochondrial disease, who harbored a population of partially deleted
      mitochondrial DNA (mtDNA) with unusual properties. These molecules were deleted
      from mtDNA positions 548 to 4,442 and encompassed not only rRNA sequences but the
      heavy-strand promoter region as well. A 13-bp direct repeat was found flanking
      the breakpoint precisely, with the repeat at positions 535 to 547 located within
      the binding site for mitochondrial transcription factor 1 (mtTF1). This is the
      second mtDNA deletion involving a 13-bp direct repeat reported but is at least 10
      times less frequent in the patient population than the former one. In situ
      hybridization studies showed that transcripts under the control of the light
      strand promoter were abundant in muscle fibers with abnormal proliferation of
      mitochondria, while transcripts directed by the heavy-strand promoter, whether of
      genes residing inside or outside the deleted region, were not. The efficient
      transcription from the light-strand promoter implies that the major heavy-and
      light-strand promoters, although physically close, are functionally independent,
      confirming previous in vitro studies.

PMID- 1996113
TI  - Retinoic acid response element in the human alcohol dehydrogenase gene ADH3:
      implications for regulation of retinoic acid synthesis.
AB  - Retinoic acid regulation of one member of the human class I alcohol dehydrogenase
      (ADH) gene family was demonstrated, suggesting that the retinol dehydrogenase
      function of ADH may play a regulatory role in the biosynthetic pathway for
      retinoic acid. Promoter activity of human ADH3, but not ADH1 or ADH2, was shown
      to be activated by retinoic acid in transient transfection assays of Hep3B human
      hepatoma cells. Deletion mapping experiments identified a region in the ADH3
      promoter located between -328 and -272 bp which confers retinoic acid activation.
      This region was also demonstrated to confer retinoic acid responsiveness on the
      ADH1 and ADH2 genes in heterologous promoter fusions. Within a 34-bp stretch, the
      ADH3 retinoic acid response element (RARE) contains two TGACC motifs and one
      TGAAC motif, both of which exist in RAREs controlling other genes. A block
      mutation of the TGACC sequence located at -289 to -285 bp eliminated the retinoic
      acid response. As assayed by gel shift DNA binding studies, the RARE region (-328
      to -272 bp) of ADH3 bound the human retinoic acid receptor beta (RAR beta) and
      was competed for by DNA containing a RARE present in the gene encoding RAR beta.
      Since ADH catalyzes the conversion of retinol to retinal, which can be further
      converted to retinoic acid by aldehyde dehydrogenase, these results suggest that
      retinoic acid activation of ADH3 constitutes a positive feedback loop regulating
      retinoic acid synthesis.

PMID- 1996114
TI  - Decreased glucocorticoid receptor activity following glucocorticoid receptor
      antisense RNA gene fragment transfection.
AB  - Depression is often characterized by increased cortisol secretion caused by
      hyperactivity of the hypothalamic-pituitary-adrenal axis and by nonsuppression of
      cortisol secretion following dexamethasone administration. This hyperactivity of
      the hypothalamic-pituitary-adrenal axis could result from a reduced
      glucocorticoid receptor (GR) activity in neurons involved in its control. To
      investigate the effect of reduced neuronal GR levels, we have blocked cellular GR
      mRNA processing and/or translation by introduction of a complementary GR
      antisense RNA strand. Two cell lines were transfected with a reporter plasmid
      carrying the chloramphenicol acetyltransferase (CAT) gene under control of the
      mouse mammary tumor virus long terminal repeat (a glucocorticoid-inducible
      promoter). This gene construction permitted assay of the sensitivity of the cells
      to glucocorticoid hormones. Cells were also cotransfected with a plasmid
      containing 1,815 bp of GR cDNA inserted in the reverse orientation downstream
      from either a neurofilament gene promoter element or the Rous sarcoma virus
      promoter element. Northern (RNA) blot analysis demonstrated formation of GR
      antisense RNA strands. Measurement of the sensitivity of CAT activity to
      exogeneous dexamethasone showed that although dexamethasone increased CAT
      activity by as much as 13-fold in control incubations, expression of GR antisense
      RNA caused a 2- to 4-fold decrease in the CAT response to dexamethasone. Stable
      transfectants bearing the GR antisense gene fragment construction demonstrated a
      50 to 70% decrease of functional GR levels compared with normal cells, as
      evidenced by a ligand-binding assay with the type II glucocorticoid receptor
      specific ligand [3H]RU 28362. These results validate the use of antisense RNA to
      GR to decrease cellular response to glucocorticoids.

PMID- 1996115
TI  - At least 27 alternatively spliced forms of the neural cell adhesion molecule mRNA
      are expressed during rat heart development.
AB  - The major membrane-associated or transmembrane isoforms of the neural cell
      adhesion molecule (NCAM) are generated by alternative splicing at the 3' end of
      the mRNA. Further diversity in NCAM structure is observed in the extracellular
      region of the polypeptide, where the insertion of additional amino acid residues
      can result from alternative splicing events occurring at the exon 7-exon 8 and
      exon 12-exon 13 junctions. Here we report the characterization of tissue-specific
      patterns of alternative splicing at the exon 12-exon 13 junction by using the
      polymerase chain reaction. Nine alternatively spliced sequences in rat heart
      between exon 12 and exon 13 were identified. Each sequence consisted of different
      combinations of the three small exons (15, 48, and 42 bp in length) and the AAG
      triplet that make up MSD1, the 108-bp muscle-specific sequence found in human
      skeletal muscle NCAM (G. Dickson, H.J. Gower, C. H. Barton, H. M. Prentice, V. L.
      Elsom, S. E. Moore, R. D. Cox, C. Quinn, W. Putt, and F. S. Walsh, Cell 50:1119
      1130, 1987). Although the rat equivalent of MSD1 (designated 15+ 48+ 42+ 3+) was
      detected in all ages of heart examined, it was only one of four or five major
      splice combinations at any given age. The only alternatively spliced sequence
      found in the exon 7-exon 8 junction of heart NCAM mRNA was the 30-bp variable
      alternatively spliced exon previously identified in rat brain. Twenty-seven NCAM
      forms with distinct sequences were found by analysis of individual NCAM
      transcripts from postnatal day 1 heart tissue for alternative splicing at the
      exon 7-exon 8 junction, the exon 12-exon 13 junction and the 3' end. Several
      combinations of splicing patterns in these three different regions of the gene
      appeared to be preferentially expressed. The observation that the expression of
      alternatively spliced forms of NCAM is developmentally regulated suggests a role
      for NCAM diversity in cardiac development.

PMID- 1996117
TI  - Rapamycin sensitivity in Saccharomyces cerevisiae is mediated by a peptidyl
      prolyl cis-trans isomerase related to human FK506-binding protein.
AB  - Rapamycin is a macrolide antifungal agent with structural similarity to FK506. It
      exhibits potent immunosuppressive properties analogous to those of both FK506 and
      cyclosporin A (CsA). Unlike FK506 and CsA, however, rapamycin does not inhibit
      the transcription of early T-cell activation genes, including interleukin-2, but
      instead appears to block downstream events leading to T-cell activation. FK506
      and CsA receptor proteins (FKBP and cyclophilin, respectively) have been
      identified and shown to be distinct members of a class of enzymes that possess
      peptidyl-prolyl cis-trans isomerase (PPIase) activity. Despite the apparent
      differences in their mode of action, rapamycin and FK506 act as reciprocal
      antagonists in vivo and compete for binding to FKBP. As a means of rapidly
      identifying a target protein for rapamycin in vivo, we selected and genetically
      characterized rapamycin-resistant mutants of Saccharomyces cerevisiae and
      isolated a yeast genomic fragment that confers drug sensitivity. We demonstrate
      that the resonse to rapamycin in yeast cells is mediated by a gene encoding a 114
      amino-acid, approximately 13-kDa protein which has a high degree of sequence
      homology with human FKBP; we designated this gene RBP1 (for rapamycin-binding
      protein). The RBP1 protein (RBP) was expressed in Escherichia coli, purified to
      homogeneity, and shown to catalyze peptidyl-prolyl isomerization of a synthetic
      peptide substrate. PPIase activity was completely inhibited by rapamycin and
      FK506 but not by CsA, indicating that both macrolides bind to the recombinant
      protein. Expression of human FKBP in rapamycin-resistant mutants restored
      rapamycin sensitivity, indicating a functional equivalence between the yeast and
      human enzymes.

PMID- 1996116
TI  - Tissue-specific transcription of the cardiac myosin light-chain 2 gene is
      regulated by an upstream repressor element.
AB  - Physiological expression of the cardiac muscle myosin light-chain 2 (MLC-2) gene
      in chickens is restricted to cardiac muscle tissue only, at least during the late
      embryonic to adult stages of development. The mechanism by which cardiac MLC-2
      gene expression is repressed in differentiated noncardiac muscle tissues is
      unknown. Using sequential 5'-deletion mutants of the cardiac MLC-2 promoter
      introduced into primary skeletal muscle cells in culture, we have demonstrated
      that a 89-bp region, designated the cardiac-specific sequence (CSS), is essential
      for repression of cardiac MLC-2 expression in skeletal muscle. Removal of the CSS
      sequence alone allows transcription in skeletal muscle cells without affecting
      the transcriptional activity of the promoter in cardiac muscle cells. DNase I
      footprinting and gel shift assays indicate that protein binding to sequences in
      the CSS domain occurs readily in nuclear extracts obtained from skeletal muscle
      but not in extracts isolated under identical conditions from cardiac muscle.
      Thus, it appears that a negative regulatory mechanism accounts for the lack of
      expression of the cardiac MLC-2 gene in skeletal muscle and that the CSS element
      and its binding proteins are important functional components of the regulatory
      apparatus which ensures the developmental program for cardiac tissue-specific
      gene expression.

PMID- 1996118
TI  - Formaldehyde cross-linking and immunoprecipitation demonstrate developmental
      changes in H1 association with transcriptionally active genes.
AB  - The in vivo association of histone H1 with specific genes in Tetrahymena
      thermophila was studied by using a simplified cross-linking and
      immunoprecipitation technique. Four genes were analyzed whose activities vary in
      three different developmental states (logarithmic growth, starvation, and
      conjugation). Hybridization of the immunoprecipitated DNA to cloned probes showed
      an inverse correlation between the level of immunoprecipitation with H1 antiserum
      and transcriptional activity. This represents the first demonstration of an
      alteration in histone H1-DNA interaction associated with developmental changes in
      transcriptional activity.

PMID- 1996119
TI  - Pancreatic beta-cell-type-specific transcription of the insulin gene is mediated
      by basic helix-loop-helix DNA-binding proteins.
AB  - The pancreatic beta-cell-specific expression of the insulin gene is mediated, at
      least in part, by the interaction of unique trans-acting beta-cell factors with a
      cis-acting DNA element found within the insulin enhancer (5'-GC CATCTG-3';
      referred to as the insulin control element [ICE]) present in the rat insulin II
      gene between positions -100 and -91. This sequence element contains the consensus
      binding site for a group of DNA-binding transcription factors called basic helix
      loop-helix proteins (B-HLH). As a consequence of the similarity of the ICE with
      the DNA sequence motif associated with the cis-acting elements of the B-HLH class
      of binding proteins (CANNTG), the ability of this class of proteins to regulate
      cell-type-specific expression of the insulin gene was addressed. Cotransfection
      experiments indicated that overexpression of Id, a negative regulator of B-HLH
      protein function, inhibits ICE-mediated activity. Antibody to the E12/E47 B-HLH
      proteins attenuated the formation, in vitro, of a previously described (J.
      Whelan, S. R. Cordle, E. Henderson, P. A. Weil, and R. Stein, Mol. Cell. Biol.
      10:1564-1572, 1990) beta-cell-specific activator factor(s)-ICE DNA complex. Both
      of these B-HLH proteins (E12 and E47) bound efficiently and specifically to the
      ICE sequences. The role of B-HLH proteins in mediating pancreatic beta-cell
      specific transcription of the insulin gene is discussed.

PMID- 1996121
TI  - Structure and expression of canary myc family genes.
AB  - We found that the canary N-myc gene is highly related to mammalian N-myc genes in
      both the protein-coding region and the long 3' untranslated region. Examined
      coding regions of the canary c-myc gene were also highly related to their
      mammalian counterparts, but in contrast to N-myc, the canary and mammalian c-myc
      genes were quite divergent in their 3' untranslated regions. We readily detected
      N-myc and c-myc expression in the adult canary brain and found N-myc expression
      both at sites of proliferating neuronal precursors and in mature neurons.

PMID- 1996122
TI  - Recommended protocols based on a survey of current practice in genotoxicity
      testing laboratories: study design.
AB  - The most commonly used genotoxicity assays for cultured mammalian cells are
      mammalian cell mutagenesis, chromosome aberrations/SCE, hepatocyte UDS, and cell
      transformation. Since their inception, protocols for these assays have been
      modified in various laboratories. It has been observed that minor but potentially
      significant method modifications frequently remain unpublished (Swierenga et al.,
      1983) but should be considered in the development of recommended protocols. The
      present study was undertaken to determine the current 'state of the art' for
      these tests. Detailed questionnaires on culture conditions and testing protocols
      for both stock and test cell populations were designed with the assistance of an
      international advisory committee and sent to all research and contract
      laboratories that could be readily identified in Canada, U.S.A. and Europe.
      Responses from 425 completed questionnaires were analyzed to determine the most
      commonly used approach and modifications for each procedural step. As expected,
      the results show a large degree of interlaboratory variation. Detailed protocols
      for conducting each assay have been prepared and include: stepwise instructions,
      precautionary measures and practical solutions to common problems associated with
      each assay; recipes for media and solutions; formulas for quantifying genotoxic
      responses; reference lists of related assays; guidelines for interpretation; and
      discussions of the applications, advantages and disadvantages of each test.

PMID- 1996120
TI  - The TIS11 primary response gene is a member of a gene family that encodes
      proteins with a highly conserved sequence containing an unusual Cys-His repeat.
AB  - The TIS11 primary response gene is rapidly and transiently induced by both 12-O
      tetradecanoylphorbol-13-acetate and growth factors. The predicted TIS11 protein
      contains a 6-amino-acid repeat, YKTELC. We cloned two additional cDNAs, TIS11b
      and TIS11d, that contain the YKTELC sequence. TIS11, TIS11b, and TIS11d proteins
      share a 67-amino-acid region of sequence similarity that includes the YKTELC
      repeat and two cysteine-histidine containing repeats. TIS11 gene family members
      are not coordinately expressed: (i) unlike TIS11, the TIS11b and TIS11d mRNAs are
      detectable in quiescent Swiss 3T3 cells and are not dramatically induced by 12-O
      tetradecanoylphorbol-13-acetate; (ii) cycloheximide superinduction does not occur
      for TIS11b and TIS11d; and (iii) unlike TIS11, TIS11b expression is extinguished
      in PC12 pheochromocytoma cells.

PMID- 1996123
TI  - Recommended protocols based on a survey of current practice in genotoxicity
      testing laboratories: I. Unscheduled DNA synthesis assay in rat hepatocyte
      cultures.
AB  - A protocol based primarily on current laboratory practices in the performance of
      the unscheduled DNA synthesis (UDS) assay with primary rat hepatocyte cultures
      has been developed. These guidelines were developed using tabulated responses to
      a detailed questionnaire completed by North American and European governmental,
      university and contract laboratories involved with the UDS test. This report
      identifies those modifications to previously described methodologies which are
      used on a regular basis and also serves to clarify confusing or inconsistent
      practices. Although this protocol pertains specifically to the use of primary rat
      hepatocyte cultures, it can be modified to incorporate other types of cells in
      which certain aspects remain the same.

PMID- 1996124
TI  - Recommended protocols based on a survey of current practice in genotoxicity
      testing laboratories: II. Mutation in Chinese hamster ovary, V79 Chinese hamster
      lung and L5178Y mouse lymphoma cells.
AB  - Laboratory protocols and guidelines have been developed for the performance of
      point mutation assays using Chinese hamster ovary (CHO) cells, V79 cells, and
      L5178Y mouse lymphoma cells. Since only minor differences in the treatment of CHO
      and V79 cells exist, these two assays could be combined in one procedural
      guideline. A second protocol was developed for the mouse lymphoma assay in order
      to incorporate concerns and methods specific to that cell type and genetic locus.
      The protocols were based primarily on current laboratory practices as determined
      by responses to a detailed questionnaire completed by North-American and European
      governmental, university and contract laboratories involved with in vitro
      mutation testing. This report identifies those modifications to previously
      described methodologies which are being used on a regular basis, provides
      recommendations, and also serves to clarify confusing or inconsistent practices.

PMID- 1996125
TI  - Recommended protocols based on a survey of current practice in genotoxicity
      testing laboratories: III. Cell transformation in C3H/10T1/2 mouse embryo cell,
      BALB/c 3T3 mouse fibroblast and Syrian hamster embryo cell cultures.
AB  - A standardized protocol and guidelines for the performance of cell transformation
      testing in mouse embryo (C3H/10T1/2), mouse fibroblast (BALB/c 3T3) and Syrian
      hamster embryo (SHE) cells have been developed. The protocol is based primarily
      on current laboratory practices as determined by responses to a detailed
      questionnaire completed by North American and European governmental, university
      and contract laboratories involved with cell transformation experimentation. This
      report identifies those modifications to previously described methodologies which
      are being used on a regular basis and also serves to clarify confusing or
      inconsistent practices.

PMID- 1996126
TI  - Recommended protocols based on a survey of current practice in genotoxicity
      testing laboratories, IV. Chromosome aberration and sister-chromatid exchange in
      Chinese hamster ovary, V79 Chinese hamster lung and human lymphocyte cultures.
AB  - A recommended protocol has been developed for chromosomal aberration and sister
      chromatid exchange assays in CHO, V79 and human lymphocyte cultures. The protocol
      was based on the responses to a detailed questionnaire completed by North
      American and European governmental, university, and contract laboratories using
      these tests. This report identifies those modifications to previously described
      methods that are used on a regular basis and clarifies confusing or inconsistent
      practices. These protocols can be modified for use in other types of cells.

PMID- 1996127
TI  - Recommended protocols based on a survey of current practice in genotoxicity
      testing laboratories: study evaluation.
AB  - The approach used in the survey of current methodologies used in mammalian cell
      genotoxicity testing (unscheduled DNA synthesis, mutation, cell transformation
      and cytogenetics testing) is discussed. The recommended protocols, described in
      the preceding papers, were developed using responses to detailed questionnaires.
      This summary outlines general observations related to the survey methodology and
      to the protocols themselves. Also discussed are the qualities of an effective
      survey; the evolution of a survey and of a protocol; and the contributions and
      limitations of this study.

PMID- 1996128
TI  - Non-random cell killing in cryopreservation: implications for performance of the
      battery of leukocyte tests (BLT), I. Toxic and immunotoxic effects.
AB  - To eliminate between-tests error in longitudinal human studies, for specimen
      sharing, convenient scheduling, etc., it is necessary for us to freeze leukocytes
      as well as non-transformed, continuous T lymphocyte (CTL) lines. Two commonly
      used cryopreservation methods were compared in terms of efficacy. Isolated
      peripheral blood mononuclear cells and CTLs were each aliquoted into three sets
      of vials. Two sets each were frozen in a 1:1 mixture of 15% DMSO in Mixed Medium
      (MM) and 20% FBS in MM using a commonly employed styrofoam freezer insert method
      for liquid nitrogen refrigerators and a programmed freezer (temperature falls at
      an optimal rate), respectively. The remaining set was held in MM with 20% FBS at
      20 degrees C during the 2-h freezing process. The cells were thawed and/or washed
      and assayed for viability and T helper (Th)/T suppressor (Ts) ratio. It is clear
      that inadequate freezing (via the styrofoam method) non-randomly damages cells of
      T cell subpopulations, Th being more sensitive than Ts. Further, it is shown that
      inadequate cryopreservation can confound results from a number of assessment
      methods owing to morphological and functional damages. The battery of leukocyte
      tests (BLT) under development in this laboratory, is designed to detect toxic,
      immunotoxic and genotoxic effects of in vivo mutagen exposure on human blood. It
      is concluded that minimization of non-random cell losses (as quantitated on the
      basis of morphology) and preservation of related regulatory cell function is
      essential if one would assess the in vivo and in vitro states of heterogeneous
      cells. Further, it is suggested that freezing methods should be used only after
      verification that selective damage to subpopulations is not occurring among cells
      that otherwise might wrongly be assumed to be intact.

PMID- 1996129
TI  - Inhalation exposure in Drosophila mutagenesis assays: experiments with aliphatic
      halogenated hydrocarbons, with emphasis on the genetic activity profile of 1,2
      dichloroethane.
AB  - A series of mutation experiments was carried out with Drosophila melanogaster
      using inhalation exposure. 1,2-Dichloroethane (DCE) and 1,2-dibromoethane (DBE)
      were active in the sex-linked recessive lethal assay (SLRLT), whereas
      dichloromethane, dibromomethane, 1,2-dichloropropane and 1,3-dichloropropane were
      not. Compared to DBE, DCE is a less potent mutagen in the SLRL system. For both
      compounds, there is no evidence of a clear-cut dose-rate effect. DCE and
      dichloromethane were also investigated in the somatic mutation and recombination
      test (SMART), with results similar to those from the SLRLT. For DCE the genetic
      activity profile was further analyzed by carrying out a sex-chromosome loss assay
      and a complementation analysis of a series of induced recessive lethal mutations.
      A review of the use of inhalation in mutagenicity assays with Drosophila shows
      that this route of exposure is an effective one. Especially with chronic exposure
      times, rather low exposure concentrations can be detected. With compounds of
      intermediate volatility inhalation is not superior to other modes of
      administration; nor is it likely to be sensitive enough for in situ monitoring.

PMID- 1996131
TI  - DNA research institute to open in Japan.

PMID- 1996130
TI  - DNA sequence analysis of revertants of the hisD3052 allele of Salmonella
      typhimurium TA98 using the polymerase chain reaction and direct sequencing:
      application to 1-nitropyrene-induced revertants.
AB  - We have used the polymerase chain reaction (PCR) to speed the DNA sequence
      analysis of revertants of Salmonella typhimurium TA98. Briefly, a crude DNA
      extract from a single colony was prepared and used in an asymmetric PCR to
      amplify a 328-bp fragment containing the hisD3052 mutation approximately in the
      center. Following ultrafiltration, the ssDNA was sequenced using an end-labeled
      probe and dideoxy sequencing. The most frequent mutation among the revertants was
      a -2 deletion of GC or CG within the sequence CGCGCGCG, which is upstream of the
      hisD3052 mutation. This deletion occurred in 38% (6/16) of the spontaneous (-S9)
      revertants and in 94% (15/16) of a set of 1-nitropyrene-induced revertants. Other
      mutations, mostly deletions but also some complex mutations (i.e., single
      mutational events involving a combination of insertions, deletions, and
      substitutions), occurred within quasipalindromic regions of DNA. Possible
      mutational mechanisms are discussed, and the results with 1-NP are compared to
      those obtained in other systems.

PMID- 1996132
TI  - Animal research. Rules arrive under a cloud.

PMID- 1996133
TI  - AAAS meeting. Presidential address sets the tone.

PMID- 1996134
TI  - . . . and at NIH.

PMID- 1996135
TI  - Antigen presentation. Later for the rendezvous.

PMID- 1996136
TI  - HIV infectivity.

PMID- 1996137
TI  - Embryonic lethality caused by mutations in basement membrane collagen of C.
      elegans.
AB  - Basement membranes are specialized forms of extracellular matrix with important
      functions in development. A major structural component of basement membranes is
      type IV collagen, a heterotrimer of two alpha 1(IV) and one alpha 2(IV) chains,
      which forms a complex, polygonal network associated with other basement membrane
      components. Here we report that the alpha 1(IV) collagen chain of Caenorhabditis
      elegans is encoded by the genetic locus emb-9. Mutations in emb-9 cause
      temperature-sensitive lethality during late embryogenesis. We have identified
      single nucleotide alterations that substitute glutamic acid for glycine in the
      triple-helical Gly-X-Y repeat region of the alpha 1(IV) collagen in three emb-9
      mutant strains. These results are direct evidence that defects in basement
      membranes can disrupt embryonic development and form a basis for the genetic
      analysis of basement membrane function.

PMID- 1996138
TI  - Novel myosin heavy chain encoded by murine dilute coat colour locus.
AB  - Hundreds of murine dilute mutations have been identified and analysed, making
      dilute one of the best genetically characterized of all mammalian loci. The
      recessive dilute (d) coat colour mutation carried by many inbred strains of mice
      produces a lightening of coat colour, caused by an abnormal adendritic melanocyte
      morphology that results in an uneven release of pigment granules into the
      developing hair shaft. Most dilute alleles (dilute-lethal) also produce a
      neurological defect, characterized by convulsions and opisthotonus, apparent at 8
      10 days of age and continuing until the death of the animal at 2-3 weeks of age.
      The discovery that the original dilute allele (now termed dilute-viral or dV) is
      the result of the integration of an ecotropic murine leukaemia provirus has
      allowed the cloning of genomic DNA and in this study complementary DNA, from the
      dilute locus. The predicted dilute amino-acid sequence indicates that dilute
      encodes a novel type of myosin heavy chain, with a tail, or C-terminal, region
      that has elements of both type II (alpha-helical coiled-coil) and type I (non
      coiled-coil) myosin heavy chains. Dilute transcripts are differentially expressed
      in both embryonic and adult tissues and are very abundant in neurons of the
      central nervous system, cephalic ganglia, and spinal ganglia. These results
      suggest an important role for the dilute gene product in the elaboration,
      maintenance, or function of cellular processes of melanocytes and neurons.

PMID- 1996140
TI  - The Xenopus localized messenger RNA An3 may encode an ATP-dependent RNA helicase.
AB  - The maternal messenger RNA An3 was originally identified localized to the animal
      hemisphere of Xenopus laevis oocytes, eggs and early embryos. Xenopus embryos
      depend on mRNA and protein present in the egg before fertilization (maternal
      molecules) to provide the information needed for early development. Localization
      of maternal mRNA gives cells derived from different regions of the egg
      distinctive capacities for protein synthesis. We show here that An3 mRNA encodes
      a protein with 74% identity to a protein encoded by the testes-specific mRNA PL10
      found in mouse, which is proposed to have RNA helicase activity. Because the gene
      encoding An3 mRNA is reactivated after gastrulation and remains active throughout
      embryogenesis, we have examined its distribution in embryonic and adult tissues.
      Unlike PL10 mRNA, which is primarily restricted to the testes, An3 mRNA is
      broadly distributed in later development.

PMID- 1996141
TI  - All that wheezes is not asthma.

PMID- 1996139
TI  - A suppressor of a yeast splicing mutation (prp8-1) encodes a putative ATP
      dependent RNA helicase.
AB  - Five small nuclear RNAs (snRNAs) are required for nuclear pre-messenger RNA
      splicing: U1, U2, U4, U5 and U6. The yeast U1 and U2 snRNAs base-pair to the 5'
      splice site and branch-point sequences of introns respectively. The role of the
      U5 and U4/U6 small nuclear ribonucleoprotein particles (snRNPs) in splicing is
      not clear, though a catalytic role for the U6 snRNA has been proposed. Less is
      known about yeast splicing factors, but the availability of genetic techniques in
      Saccharomyces cerevisiae has led to the identification of mutants deficient in
      nuclear pre-mRNA splicing (prp2-prp27). Several PRP genes have now been cloned
      and their protein products characterized. The PRP8 protein is a component of the
      U5 snRNP and associates with the U4/U6 snRNAs/snRNP to form a multi-snRNP
      particle believed to be important for spliceosome assembly. We have isolated
      extragenic suppressors of the prp8-1 mutation of S. cerevisiae and present here
      the preliminary characterization of one of these suppressors, spp81. The
      predicted amino-acid sequence of the SPP81 protein shows extensive similarity to
      a recently identified family of proteins thought to possess ATP-dependent RNA
      helicase activity. The possible role of this putative helicase in nuclear pre
      mRNA splicing is discussed.

PMID- 1996142
TI  - A case of leukemia due to HTLV-1. A virus of regional significance.

PMID- 1996143
TI  - Physicians and nuclear war.

PMID- 1996144
TI  - A nurse's view of the nursing shortage.

PMID- 1996145
TI  - Mental illness. Mind and body.

PMID- 1996146
TI  - Dedicated ophthalmic research.

PMID- 1996148
TI  - Comments on the special issue on preventive medicine (November 1990)

PMID- 1996147
TI  - The halcyon days of youth, Part II. The second year at the "new" UNC Medical
      School.

PMID- 1996149
TI  - End-of-life decisions.

PMID- 1996150
TI  - Forecasting requirements for health care personnel.
AB  - Accurate forecasting of requirements for health care personnel is an important
      part of avoiding significant imbalances that create costly inefficiencies in
      health care markets. Manpower shortages threaten access, quality, and costs of
      health care. This article reviews five general approaches previously used to
      determine manpower requirements. Suggestions are made for the analytic components
      of a comprehensive model for identifying significant imbalances in supply or
      demand for health care workers.

PMID- 1996152
TI  - Negotiating a severance agreement.
AB  - A severance agreement is a valuable and negotiable benefit for the nurse
      executive in transition. Knowing which clauses to request and which to avoid
      helps the nurse executive provide for a secure job transition.

PMID- 1996151
TI  - Who knows?

PMID- 1996153
TI  - Nurse entrepreneurship: opportunities in acute care hospitals.
AB  - "Heartcheck," a new hospital-based program initiated by a nurse clinician,
      focuses on patient needs. Factors related to the program's success are evaluated
      from an entrepreneurial perspective.

PMID- 1996155
TI  - The introduction of new technology on the nursing unit.

PMID- 1996154
TI  - What does a military nursing shortage mean to us?
AB  - The current nursing shortage makes U.S. military medical readiness questionable.
      Legislative initiatives for attracting nurses to the military and reserves are
      being employed. In spite of these efforts, plans are underway to draft nurses
      during a military emergency.

PMID- 1996156
TI  - Individualized medication sheets.

PMID- 1996158
TI  - Optimism: an essential skill for the nurse manager.

PMID- 1996157
TI  - Patient care automation: the future is now. Part 5. The role of technology.
AB  - A number of technical issues have been considered in this article; such issues
      need to be considered in a patient care systems procurement after the philosophic
      base of the system has been established.

PMID- 1996159
TI  - [Eurothemes. A Hungarian internist: 'The Dutch physician has a lot of autonomy].

PMID- 1996160
TI  - [The duty to render aid].

PMID- 1996161
TI  - [Ruptures of the patellar ligament].

PMID- 1996162
TI  - [Current insights in the pathogenesis and treatment of duodenal ulcer].

PMID- 1996163
TI  - [Asthma and hypersensitivity for acetylsalicylic acid].

PMID- 1996164
TI  - [Hereditary cerebral amyloid angiopathy and Alzheimer's disease].

PMID- 1996165
TI  - [The oral cholera vaccine project; the first 3 years of field work in
      Bangladesh].

PMID- 1996166
TI  - [Refocusing on the gynecological and obstetrical consequences of intrauterine
      exposure to diethylstilbestrol (DES)].
AB  - The oncological and obstetrical follow-up is described of 321 patients who
      presented between 1981 and 1988 in the St Radboud Hospital with a history of
      intrauterine diethylstilbestrol(DES) exposure. In 45 out of 321 cases cytological
      abnormalities were found including 20 cases of cervical intraepithelial neoplasia
      (CIN). No relation could be established between CIN and the extension of the
      cervical adenosis. Twenty-two percent of 87 evaluable pregnancies terminated in
      spontaneous abortion, 13 percent of the patients delivered immaturely and 27
      percent prematurely. These percentages were significantly higher than in the rest
      of the hospital population. The consequences of intrauterine exposure to DES are
      discussed. Full examination of the patients is advised, including colposcopy and
      hysterosalpingography. If abnormalities are present it is advised to offer a
      timely cerclage in case of pregnancy.

PMID- 1996167
TI  - [Course and distribution of mortality of pleural mesothelioma in The Netherlands,
      1970-1987].
AB  - In this article the sex- and age-specific trends and geographical distribution of
      asbestos related pleural mesothelioma mortality in the Netherlands between 1970
      and 1987 are investigated. For men total mortality increased from 10.8 per
      million during 1970-1978 to 20.9 per million during 1979-1987. The highest
      mortality occurred with 147.7 per million in 1987 in the age group between 65 and
      74 years. Mortality rates for the age group between 55 and 64 years amounted to
      96.5 per million in 1987. The geographical distribution over the country showed a
      strong concentration of male mesothelioma cases in the regions with many
      harbours, shipyards and heavy industries round Amsterdam, IJmuiden, Rotterdam,
      Dordrecht and Walcheren. Using linear regression techniques, it was calculated
      that several thousands new mesothelioma cases will occur in the Netherlands
      during the next two decades. A significant decrease in mesothelioma mortality can
      not be expected before 2010.

PMID- 1996168
TI  - [The prevalence of urinary incontinence in elderly women].
AB  - On the basis of a survey in March 1989 among non institutionalized women aged 60
      years and older living in Amstelveen, the prevalence of urinary incontinence was
      estimated. Also investigated were factors potentially associated with urinary
      incontinence, as well as the psychosocial impact on daily living activities. The
      sample comprised 1049 women; 719 postal histories were completed. Statistical
      analyses involved chi 2 and chi 2 trend tests, and the influence of determinants
      was assessed with multivariate logistic regression. The prevalence of urinary
      incontinence was 23.5%, with a slight increase with increasing age. Daily urine
      loss was reported in 14.0% of all women. Significantly associated with urinary
      incontinence were an increased diurnal as well as nocturnal voiding frequency,
      immobility and use of diuretics. Urinary incontinence actually interfered with
      daily living activities in 65.3% of the women.

PMID- 1996169
TI  - January 17, 1991.

PMID- 1996170
TI  - Curriculum quandary.

PMID- 1996171
TI  - AIDS: advocacy and activism.

PMID- 1996172
TI  - Assessment of outcomes: the design and use of real and simulation nursing
      performance examinations.
AB  - Lenburg and Mitchell tell us the time for student outcome assessment has arrived.
      They examine the philosophic assumptions underlying this system and share the
      experience gleaned by the New York Regents External Degree programs. Testing
      options ranging from observed care of real patients to patient simulations to
      interactive video exams are discussed.

PMID- 1996173
TI  - A women's health course with a feminist perspective: learning to care for and
      empower ourselves.
AB  - Boughn presents an interesting linkage between caring and empowerment in a
      feminist perspective. To emphasize the feminist position, Boughn applies this
      outlook to a course on women's health issues. While her first group of students
      happened to consist entirely of women, she notes that men could profit from the
      same perspective, the same content.

PMID- 1996174
TI  - Nursing skills necessary for competency in the high-tech health care system.
AB  - Neighbors, Sullivan, and Eldred tell us how schools of nursing and institutions
      of nursing practice conform--or fail to conform--in regard to what constitutes
      basic nursing procedures. Are schools leaving the new graduate unprepared for
      everyday practice? A survey of association degree schools is revealing.

PMID- 1996175
TI  - Helping nursing students communicate with high-risk families. An educator's
      challenge.
AB  - Lerner and Byrne advocate that students care for high-risk families during their
      maternity experience. Communication problems, client resistance, and newness of
      maternal care skills make this assignment a challenge for students and faculty as
      well.

PMID- 1996176
TI  - 1990-91 update: how each state stands on legislative issues affecting advanced
      nursing practice.

PMID- 1996177
TI  - Occupational health: how work environments can affect reproductive capacity and
      outcome.
AB  - This article presents a compilation of descriptive data on how work environments
      can affect reproductive capacity and outcome. A thorough background in issues
      relevant to reproductive health provides a basis for understanding the effects of
      work on pregnancy and the effects of pregnancy on work performance. The physical
      changes of pregnancy and the sequential events by trimester are discussed in
      relation to work demands and risks. A review of specific job-related risks is
      also presented, including various chemicals, infections and environmental agents.
      A third section focuses on the clinical application of taking occupational and
      reproductive histories, and on guidelines for preconception and pregnancy
      counseling.

PMID- 1996178
TI  - Ectopic pregnancy: clinical evaluation, diagnostic measures and prevention.
AB  - In recent years, the number of ectopic pregnancies in the United States has
      tripled, reaching epidemic proportions. This article reviews newly identified
      risk factors and procedures for clinical evaluation. It explains current
      diagnostic measures, including use of ultrasound technology and determination of
      serum human chorionic gonadotrophin levels. Differential diagnosis, clinical
      profiles, and updated medical and surgical treatments are described.
      Postoperative care is addressed, both from a physical and emotional standpoint.
      Prevention is discussed, and the role of the nurse practitioner in promoting
      women's health is outlined, including incorporation of tubal health histories
      into women's health care to more carefully identify women at risk for this
      complication of pregnancy.

PMID- 1996179
TI  - Non-nurse college graduates: a new resource for future nurse practitioners.
AB  - Non-nurse college graduates are admitted to the master's of science in nursing
      (MSN) degree program at the University of Tennessee, Knoxville (UTK). Over the
      years, a majority of these non-traditional students have chosen the family nurse
      practitioner clinical concentration. The purpose of this study was to compare non
      traditional and traditional family nurse practitioner (FNP) graduates in terms of
      academic and career-development characteristics. The study population consisted
      of all 91 (48 non-traditional and 43 traditional) UTK FNP graduates from 1981 to
      1986. Little difference was found between the two groups' academic success in the
      program, self-perceptions of clinical preparedness for practice, current
      participation in the workforce, and self-perceptions of acceptance from
      administrators, other nurses and physicians in current work settings. Several
      notable differences between the two groups were found. The non-traditional FNP
      graduates had higher Graduate Record Examination (GRE) mean scores. More non
      traditional than traditional FNP graduates were employed initially as nurse
      practitioners. Similarly, more non-traditional FNP graduates were currently
      employed as nurse practitioners in primary health care settings. Fewer non
      traditional FNP graduates expressed satisfaction with their initial or current
      nursing positions. In regard to career goals, however, more of the non
      traditional FNP graduates stated their intent was to be functioning as nurse
      practitioners in the future. Non-nurse college graduates with an interest in
      health care are a rich resource from which to recruit practicing nurse
      practitioners for the future.

PMID- 1996180
TI  - [Dominican Republic. Imagine five years...].

PMID- 1996181
TI  - [Drug Caution Code].

PMID- 1996182
TI  - [Resource persons].

PMID- 1996183
TI  - [Drop by drop].

PMID- 1996184
TI  - Full steam ahead. Opening speech by the OIIQ's president, Jeannine Pelland, at
      the 70th annual general meeting.

PMID- 1996185
TI  - [Community and institutional help: a spectrum for new parents].

PMID- 1996186
TI  - Nutrition in pregnancy in the Wellington region.
AB  - The diets of 115 pregnant women in the Wellington region were assessed for
      nutrient intake using 24 h dietary recall. Assessment was performed in both the
      second and third trimester. Women came from three ethnic groups, European (61),
      Maori (29) and Pacific Islanders (25). Comparisons of nutrient intake were made
      between these groups. The overall energy intake was similar between the groups
      (range 4.8-19.7 MJ/d) but Maori (p less than 0.05) and Pacific Islanders (p less
      than 0.02) had a significant decrease in energy intake from second to third
      trimester. Pacific Islanders consumed significantly more starch (121 g/d, p less
      than 0.05) whereas Maori women consumed significantly more sucrose (86 g/d, p =
      0.0002). The mean intake in Pacific Islanders contained significantly less
      calcium (882 mg/d, p = 0.0002) and zinc (9.0 mg/d, p = 0.014). Forty-four percent
      Europeans, 28% Maori and 51% Pacific Islanders had an estimated iron intake below
      the minimum safe intake for pregnancy. However dietary iron intake did not relate
      to the presence of anaemia nor whether iron supplements were given.

PMID- 1996187
TI  - Trial of slow release diltiazem for essential hypertension in general practice.
AB  - In New Zealand diltiazem has been approved since 1984 for the treatment of angina
      pectoris and was available only as short acting tablets. This study was a trial
      of a slow release formulation in the treatment of hypertension. A single blind
      placebo controlled study was undertaken on 24 patients in general practice using
      a once daily dose with a maximum of 360 mg. The mean fall in resting supine
      diastolic blood pressure was 17.3 mmHg, 95% CI 14.4 to 20.2; t = 12.2, df = 23, p
      = 0.0001. Twelve patients (50%) achieved a fall in diastolic pressure to 90 mmHg
      or less with the minimum dose (120 mg) while 19 patients (79%) achieved this
      level with up to 360 mg daily and 22 patients (92%) had a fall of diastolic
      pressure of 10 mmHg or more. One patient was withdrawn because of a rash. Other
      adverse reactions were mild and usually tolerable.

PMID- 1996188
TI  - The changes in smoking habits in a rural adolescent population, 1975-89.
AB  - A survey of tobacco smoking habits in 435 adolescent schoolchildren was
      undertaken in 1989 in a rural, largely Maori population. The survey questionnaire
      was identical to that used in a 1975 survey at the same school. Among this group,
      Maori still smoke more often than nonMaori (36.6% vs 25.2%), and currently this
      is particularly true for females (46.7% vs 31.3%). Among currently smoking Maori,
      both in males and females cigarette consumption has significantly risen (median
      per week: 15 vs 30), despite an overall fall in the proportion of the groups who
      report smoking within the previous month (57.1% vs 36.6%). As a result, there are
      now significantly more smokers in the highest consumption group than previously
      (7.0% vs 12.6%), particularly among Maori females (7.5% vs 16%). Similar but
      lesser trends have occurred among nonMaori, with the exception that in addition
      to cigarette consumption, the proportion of females currently smoking has also
      tended to rise. There remains considerable cause for concern about smoking among
      this younger age group.

PMID- 1996189
TI  - Hospital outpatient costs for patients with HIV infection.

PMID- 1996190
TI  - Medical discipline.

PMID- 1996191
TI  - Melanoma and fatty acids.

PMID- 1996192
TI  - Working party: management of hepatitis B carriers.

PMID- 1996193
TI  - [Coronary revascularization in post-infarction patients].
AB  - Authors report the type of revascularization, the result of noninvasive and
      invasive investigations carried out 6-9 months after surgery, improvement of
      functional status of 56 postinfarction patients with recurrent angina pectoris.
      They conclude, that recoronarography performed in 12 patients revealed diminished
      patency rate compared to the estimated predictive one, especially in those, where
      complete revascularization was considered to have been carried out. Ejection
      fraction, wall motion score by ventriculography and echocardiography did not seem
      to improve significantly. However Dipyridamol Thallium scintigraphy showed marked
      improvement in perfusion in all cases. NYHA functional status has noticeably
      improved in the reexamined patients.

PMID- 1996194
TI  - [The effect of chronic alcohol consumption on blood pressure].
AB  - In 1984, a hypertension screening programme was carried out on 13,772 adult
      subjects in conjunction with a radiological tuberculosis project in the Hungarian
      town of Csongrad. Among other factors, the effects of a long-lasting and heavy
      alcohol intake on blood pressure levels were investigated. 21.4% of the men and
      2.3% of women admitted to being regular alcohol consumers. Direct and significant
      relationships were found between the quantity of alcohol consumed and both the
      systolic (p less than 0.001) and diastolic (p less than 0.05) blood pressures.
      The prevalence of hypertension (WHO criteria) was higher in heavy drinkers
      (29.9%) than in abstinent subjects (20.5%, p less than 0.001). When participants
      were subgrouped according to age groups only the men provided sufficient data.
      The systolic blood pressure of heavy drinkers was elevated as compared with that
      of non-drinkers.

PMID- 1996195
TI  - [Advantages of rooming-in care of mother and child in the control of enteric
      epidemics in neonatal departments].
AB  - The hygienic advantages of the rooming-in system is described by the authors. The
      conditions of their institution are given in this country setting. Major
      conclusions from enteritis epidemic in neonatal wards are: long-lasting
      hospitalization and bottle feeding increases the incidence of enteric infections.
      In the spreading of this epidemic the hands of the nursing staff play a decisive,
      very important role. The rooming-in system helps in defeating the enteric
      infections, as a possibility for isolation, by decreasing the chance of cross
      infections, the satisfying breast feeding makes the supplementary food
      unnecessary, thus preventing the infection of the alimentary tract.

PMID- 1996196
TI  - [Holt-Oram syndrome].
AB  - Authors report on the genetic epidemiologic investigation of the upper limb-
      cardiovascular (Holt-Oram) syndrome. The source of cases was the material of the
      Hungarian Congenital Malformation Registry. Birth prevalence was 0.95/100,000
      total births. 85% of all cases proved to be consequences of new mutations, hence
      the mutation rate was 4.07 x 10(-6) +/- 3.12 x 10(-6).

PMID- 1996197
TI  - [Clinical use of aminoglycoside antibiotics].

PMID- 1996198
TI  - [Vilma Hugonnai, the first Hungarian woman-physician].

PMID- 1996199
TI  - [Curiosities from old Hungarian medical libraries. Marginal notes in a Pax
      Corporis volume from 1695].

PMID- 1996200
TI  - [Medical history writing from the middle of the 20th century].

PMID- 1996201
TI  - [Secondary membranous glomerulonephritis].
AB  - Following 689 percutaneous renal biopsies, membranous glomerulonephritis was
      proved in 68 patients. In 16 (23.5%) an underlying primary disease was verified,
      and thus the glomerulonephritis the secondary form. The primary disease was SLE
      in 5 cases, diabetes mellitus in 5 cases, rheumatoid arthritis in 3 cases,
      chronic active hepatitis in 2 cases, an ulcerative colitis and eosinophilic
      angiolymphoid hyperplasia in 1 patient. As initial sign, nephrotic syndrome
      emerged in 87.5% of the 16 cases. Microscopic haematuria was observed in half of
      the patients, as was hypertension, while acute renal failure presented in only 1
      case. Histologically, in 13 cases the predominance of early glomerular
      alterations was characteristic, while in 9 cases the picture proved to be
      equivocal and accompanied by some degree of interstitial alterations. During
      combined treatment, remission was achieved in 75%. Two patients with SLE died,
      but not as a consequence of renal failure. Transient side-effects of the
      treatment were registered in 5 cases. The principal pathogenetic and clinical
      differences between the individual secondary nephritis forms, and the difficulty
      of their differentiation from the idiopathic cases, even on repeated examination,
      are emphasized. In 3 patients the possibility of secondary renal processes was
      suggested by the histological picture, and this was proved by the detailed
      clinical findings.

PMID- 1996202
TI  - [Perioperative myocardial infarct].
AB  - Retrospective analysis has been carried out with the surgical material of 9 years
      in the wards of surgical character of a county hospital to determine the
      incidence and main clinical characteristics of perioperative myocardial
      infarction. Data of 61 patients were processed in order to answer the questions.
      Age, arteriosclerosis causing disturbance of organ perfusion and the change of
      blood pressure in the perioperative period play the main role in the development
      of this complication of high mortality. Detailed clarification of the coronary
      state before the elective operation, a possible aortocoronary bypass operation
      appear to prevent most effectively the pathological picture.

PMID- 1996203
TI  - [First isolation of Borrelia burgdorferi (Lyme spirochaeta) from ticks in
      Hungary].
AB  - 31 field collected Ixodes ricinus adult ticks were investigated for the Lyme
      disease spirochete. 5/31 Ixodes ricinus contained Borrelia burgdorferi. The
      spirochete was successfully cultivated in four cases, and they were found in two
      ticks by immunofluorescence technique and dark field microscopy, as well. Two of
      the isolated strains were tested by Western blot. The antigen pattern in both
      strains showed marked bands in 41 and 60 kD antigen, but only a week band
      appeared at 32 kD, with the lack of the OspB. The mechanism of infection and the
      way of prevention is discussed.

PMID- 1996204
TI  - [Pulsatile gonadotropin-releasing hormone substitution following excision of a
      craniopharyngioma with suprasellar invasion].
AB  - Craniopharyngeoma growing suprasellary attacks the medio-basal region of
      hypothalamus, that leads to the stopping of the production of gonadotropin
      releasing hormone. In connection with the case of a 15-year-old girl who had
      partial extirpation of craniopharyngeoma the authors write about the favourable
      endocrine effect of pulsatile gonadotropin releasing hormone treatment. Through
      giving gonadotropin releasing hormone every 90 minutes in 20 micrograms doses
      menstruation cycle and ovulation was performed. Beside surgical treatment
      hormonal substitution plays an important role in the treatment of additional
      endocrine symptoms.

PMID- 1996205
TI  - [Inflammation of the small pelvis caused by Actinomycosis infection].
AB  - Authors report their observations obtained in the course of treatment of 36
      patients suffered from pelvic Actinomycosis. The course of disease of patients
      treated with pelvic inflammatory disease during a period of five years was
      compared with the occurrence at IUD users and non-users. The interdependence of
      occurrence of Actinomycosis, as well as previous deliveries, abortions and the
      period of use of IUD was investigated retrospectively. Difference was made
      between primary and secondary Actinomycosis. Authors investigated the methods of
      diagnostics of Actinomycosis and those of prevention and treatment. It was stated
      that because of pelvic Actinomycosis at IUD users the surgical intervention was
      not higher than the PID caused by other pathogenic. microorganisms.

PMID- 1996206
TI  - [Reoperation in thoracic outlet syndrome].
AB  - Questions of surgical treatment are dealt with shortly when analyzing
      reoperations in cases of thoracic outlet syndrome. Transaxillary first rib
      resection is considered as a favourable solution. Authors believe that in the
      overwhelming majority of recurrences it is the lack of resection or insufficient
      resection of the first rib that can be considered as responsible for it. By the
      way of conclusion the importance of medical gymnastics and physiotherapy to be
      started in the early postoperative period is pointed out.

PMID- 1996207
TI  - [Determination of cyclosporin concentration in blood by radioimmunoassay].
AB  - Cyclosporin A treatment is unimaginable without continuous and periodical
      monitoring of the blood cyclosporin concentration. One of the best methods for
      measuring is the radioimmunoassay, because this method makes possible the
      monitoring of a large number of samples with good sensitivity. The method is
      suitable for measuring either only the cyclosporin A concentration (specific
      monoclonal antibody) or the cyclosporin A and its metabolites (nonspecific
      monoclonal antibody). The use of 125I labelled tracer has several advantages such
      as increased sensitivity, fast sample counting and so fast measuring of the
      concentrations.

PMID- 1996208
TI  - [Dermabrasion for tattoo removal complemented by cell suspension for wound
      healing].
AB  - The authors completed the surgical removal of tattoos with epithelization using
      epidermal cell suspension. The cells were separated from the removed tattood
      skin. The advantages of this method that there is no need for separate donor
      skin, the procedure is cheap and good epithelization can be achieved.

PMID- 1996209
TI  - [Comparative analysis of three hospital systems].
AB  - The author compares the hospital system of Hungary with that of New Jersey (USA)
      and that of the Netherlands. The study discusses, among others, the issue on
      beds, size, ownership, management, personnel and financing of hospitals. There is
      a significant deviation in the distributional structure of hospital beds, costs
      indicators, wage-level and the size of nursing personnel. Nursing homes do not
      exist in Hungary. This study presents a basis for the working out of a local
      hospital reform.

PMID- 1996210
TI  - [Neonatal hypoxic myocardial lesion].
AB  - Five patients suffering from transient myocardial ischemia of the newborn are
      discussed. The role of two-dimensional doppler-echocardiography is emphasized in
      establishing the diagnosis. Tricuspid insufficiency due to perinatal asphyxia can
      be detected easier by ultrasound than by any other cardiac examination. Cardiac
      failure as a result of hypoxic myocardial ischemia is usually reversible and
      responds well to anticongestive treatment and administration of oxygen. On the
      other hand some cases can be fatal, histopathologic examination on the heart
      shows similarity to myocardial infarction.

PMID- 1996211
TI  - [Cutaneous gangrene secondary to nephrogenic hyperparathyroidism].
AB  - Ischemic cutaneous gangrene is described in a 44 years old woman-patient, which
      could be attributed to metastatic calcinosis developed on account of secondary
      hyperparathyroidism. Recovery was obtained by subtotal parathyroidectomy, as well
      as by local treatment. For naming of the characteristic syndrome mentioned above,
      "uremic gangrene syndrome" is recommended.

PMID- 1996212
TI  - Slipped capital femoral epiphysis.
AB  - Slipped capital femoral epiphysis (SCFE) is an unusual disorder in which the
      epiphysis of the proximal femur slips through the growth plate in a posterior
      direction. Significant derangement of hip function results and can be accompanied
      by two complications: avascular necrosis and chondrolysis. The cause remains
      elusive although many theories have been advanced. This article provides an
      overview of the disease process, diagnostic guidelines, and current treatment
      considerations. A case study is included.

PMID- 1996213
TI  - Nursing care for multiple sclerosis.
AB  - Multiple sclerosis (MS) is a chronic, complex neurologic disease of unknown
      origin characterized by exacerbations and remissions. This demyelinating disease
      of the central nervous system primarily affects young adults. Lately, research
      has provided new and important findings regarding various etiologic
      possibilities. Knowledge of comprehensive care is necessary not only for acute
      hospitalizations but also for individualizing daily home activities for MS
      patients and their families.

PMID- 1996214
TI  - Accepting or rejecting assignments.
AB  - In the best of all worlds, professional nurses will assume the responsibility and
      accountability for their actions in their work place. Professionals will
      establish line of communication with supervisors and administrators that function
      on a regular basis and not from crisis to crisis. By recognizing potential
      disasters and planning for them, perhaps nurses will not be put in the difficult
      position of having to decide about accepting or refusing an assignment.
      Ultimately, individual nurses in support of each other can improve patient care
      and their professional working environment.

PMID- 1996215
TI  - Malignant hyperthermia.
AB  - Malignant hyperthermia (MH) is an acute syndrome that occurs in genetically
      susceptible persons who have been exposed to certain anesthetic agents. It can
      also be induced by catecholamines activated by stress. One in 200 people is at
      risk for developing malignant hyperthermia. The mortality rate may be as high as
      15%. A thorough history obtained before surgery is of extreme importance to
      prevent an MH crisis and in the management of those susceptible to the disorder.
      If MH is suspected a diagnosis, which can be confirmed by muscle biopsy, should
      be ruled out before surgery.

PMID- 1996217
TI  - Osteopathic medicine.
AB  - Osteopathic physicians are licensed physicians practicing in all 50 states. This
      article describes the philosophy of Osteopathic Medicine and reviews the
      objective support for it. Special emphasis is placed on somatic, visceral, and
      psychologic interaction. Specific examples of Osteopathic Manipulative Therapy
      (OMT) are also described.

PMID- 1996216
TI  - The patient in a halo brace: striving for normalcy in body image and self
      concept.
AB  - This retroactive descriptive study identified specific psychologic concerns and
      needs of halo patients related to the halo experience. Thirty-eight subjects who
      had a halo brace applied in the previous 8 years completed the questionnaire.
      Responses were categorized and analyzed using nursing diagnoses. Results showed
      that distortion of body image, distortion of self-concept, grieving for losses,
      and striving for normalcy are among the phenomena experienced by halo patients.

PMID- 1996218
TI  - Product line management.
AB  - The application of Product Line Management to the health care industry in the
      United States is an effort to use a management approach from the business world
      that aims at implementing, maintaining, and enhancing productivity without
      compromising quality patient care. Product Line Management is an opportunity for
      the nurse in management to develop a business acumen that will directly influence
      patient outcomes. Under this concept the product, is defined, priced, marketed
      and sold. The result is the ability to secure a competitive edge in the health
      care marketplace that not only allows us to survive, but to thrive.

PMID- 1996219
TI  - Morphine: an old drug reviewed and reexamined.

PMID- 1996220
TI  - Legislative process.

PMID- 1996221
TI  - Diversity: an opportunity for empowerment.

PMID- 1996222
TI  - Creative solutions to New Jersey's nursing shortage: the story of the NIRA
      Grants.

PMID- 1996223
TI  - How will Kati nurse?

PMID- 1996224
TI  - [Tobacco or living? Decrease in smoking in Iceland 1985-1990].
AB  - In 1985 a new tobacco act was passed in Iceland, which prescribed inter alia that
      warnings be printed on packages of tobacco goods. A prohibition on advertisement
      for tobacco has since been imposed; information on the injurious effects of
      tobacco has been disseminated in the schools and via TV. A law which limits
      smoking at work places and indoors in public buildings has also been introduced.
      Smoking habits have changed in the last five years. The number of daily smokers
      has fallen from 40.0 to 32.5 per cent, and rules concerning smokeless hospitals
      are coming into force. The authors believe that doctors and hospitals should lead
      the way if we are to reduce smoking in the society.

PMID- 1996225
TI  - [Intra-osseous infusion--a simple, rapid and lifesaving method].
AB  - One of the major challenges in the initial treatment of critically ill or injured
      patients is the establishment of a well functioning intravenous access. This can
      be very difficult in patients with circulatory collapse, and almost impossible in
      infants. Central venous cannulation is time-consuming and requires skill. Nor can
      intratracheal and rectal administration of drugs and fluids fully replace the
      intravascular route. In such situations the old but forgotten technique of
      intraosseous infusion represents an elegant and easy way of gaining rapid
      intravascular access. The method is simple, safe and almost foolproof, and can
      easily be performed under field conditions, e.g. by paramedical personnel. Very
      few contra indications exist, and the success rate even by untrained personnel is
      high. In this review the physiological aspects and the technique itself is
      discussed and illustrated by case reports.

PMID- 1996226
TI  - [Laxity in the metacarpophalangeal joint of the thumb].
AB  - Instability in the thumb is one of the most frequent sport injuries following
      trauma with the finger in abducted position. Investigation of the stability
      includes pinch-hold test and conventional X-ray examination to visualize bone
      avulsion fractures. Occasionally radiologic stress test of stability or
      arthrography should be performed in cases of doubt. Surgical intervention must be
      performed in all cases with instability or uncertain clinical manifestation.
      Especially the distal rupture with folding of the ulnar collateral ligament, the
      Stener lesion, should be detected to avoid healing of the ligament to the first
      metacarpal bone. Any form of surgical treatment must be immobilized in a cast for
      4 to 6 weeks. The tendency is to perform direct suture of capsules and ligaments
      for the first posttraumatic weeks, tenoplasty operations before 2-3 months and
      fusion in cases with persistent, chronic instability.

PMID- 1996227
TI  - [Infertility and a mild degree of endometriosis].
AB  - Laparoscopy of barren women in whom no other causes of impaired fertility can be
      demonstrated frequently reveals minimal areas of endometriosis. This review of
      the literature on infertility and mild endometriosis shows that there is no
      convincing study of the effectiveness of either surgical or specific forms of
      medical therapy for infertility and mild endometriosis. Continual treatment with
      gestagen may be tried. If this does not succeed the GIFT method may be applied.

PMID- 1996228
TI  - [Ischemic myocardial disease].

PMID- 1996229
TI  - [A deficit in women--a contributory reason for an imbalance in society].
AB  - The author has carried out a comparison between the female/male ratio (x 100) in
      different age groups in the Nordic countries and Greenland. The ratio was much
      the same, about 95, up to the age 45-50 years. But there were two exceptions, the
      Faroe Islands and Greenland. Here the excess of males aged 20-49 years was much
      higher than in the other countries. In Greenland for this was mainly due to an
      immigration of adult males, and the female/male ratio was 75.4. Some possible
      influences on the society are discussed.

PMID- 1996230
TI  - [Medical education in the USSR. Possibility of cooperation with Scandinavia].
AB  - The article describes the medical training at the basic and the advanced levels
      in the USSR together with the cooperation agreements in the field of education
      which have been signed by the Nordic Federation for Medical Education and the
      Postgraduate Medical Institute (USSR, Leningrad).

PMID- 1996231
TI  - [Reocclusion following thrombolytic treatment in acute myocardial infarct].
AB  - Currently there are five thrombolytic substances undergoing evaluation:
      streptokinase, tissue plasminogen activator, acylated plasminogen streptokinase
      activator complex, urokinase and single chain urokinase plasminogen activator.
      Equal results for mortality reduction (25 per cent) and reocclusion (6-24 per
      cent) has been reported in the literature for the five substances. Reocclusion
      can be divided into an early (greater than 24 hours) and a late phase. The early
      phase is most likely due to an imbalance between thrombolysis and the formation
      of a thrombus. During late reocclusion there is formation of a thrombus on the
      underlying coronary plaque or residual thrombotic mass, following thrombolytic
      therapy. The residual stenosis following thrombolysis seems to be the most
      important prognostic factor for reocclusion. A residual stenosis of over 75 per
      cent is unfavourable. Early reocclusion is prevented through simultaneous
      antithrombotic and thrombolytic therapy. Patients with a residual stenosis of
      over 75 per cent should be considered for some sort of active intervention to
      prevent late reocclusion.

PMID- 1996232
TI  - [Interaction between the arterial wall and thrombocytes in smokers].
AB  - Smoking is per se a major risk factor in cardio-vascular diseases. It causes
      atherosclerosis and blockage particularly in the aorta and the leg arteries. The
      components of tobacco smoke damage the endothelium, increase arterial
      contractility, and accelerate the formation of plaque therein. The mechanisms of
      the effect of smoking on the genesis of atherothrombotic diseases have been
      studied in inter alios identical twins where the one smokes and the other does
      not. Smoking activates the sympathetic nerves and affects their regulation.
      Tobacco smokers show signs of activated thrombocyte function and increased
      sensitivity to vasoconstriction, which provokes a counter-reaction in the
      arterial walls. The observations emphasize the importance of vaso-active agents
      for the development and complications of atherosclerosis.

PMID- 1996233
TI  - AIDS profile has changed.

PMID- 1996234
TI  - Gulf war. Caring for burns. Interview by Pamela Holmes.

PMID- 1996236
TI  - Fair stage?

PMID- 1996235
TI  - A slippery slope?

PMID- 1996237
TI  - Sharp turn.

PMID- 1996239
TI  - Our time has come.

PMID- 1996240
TI  - Communication. On call.

PMID- 1996238
TI  - The blame game.

PMID- 1996241
TI  - Communication. Triage by telephone.

PMID- 1996242
TI  - Communication. A listening ear. Interview by Ian McMillan.

PMID- 1996243
TI  - How safe is your ward?

PMID- 1996244
TI  - Patients' best friend?

PMID- 1996245
TI  - Making sense of ... sensory deprivation.

PMID- 1996246
TI  - Prepare for PREPP--4. Take five.

PMID- 1996247
TI  - Bessie bounces back. Care study.

PMID- 1996248
TI  - Follow-up of screening for hyperlipidaemia.

PMID- 1996250
TI  - Nurse education. The American revolution.

PMID- 1996249
TI  - Ignorance my enemy.

PMID- 1996251
TI  - Nurse education. How to organise ... briefing days.

PMID- 1996253
TI  - Mental handicapped nursing. Sexual abuse. Speaking out.

PMID- 1996252
TI  - Mental handicapped nursing. Sexual abuse. Facing facts.

PMID- 1996254
TI  - Careers focus. Atlantic Crossing.

PMID- 1996255
TI  - Gulf war. The chemical threat.

PMID- 1996256
TI  - Casualty alert.

PMID- 1996257
TI  - The great divide.

PMID- 1996258
TI  - Sweet hope.

PMID- 1996260
TI  - Care for the poorest.

PMID- 1996259
TI  - The crisis within.

PMID- 1996261
TI  - The other war.

PMID- 1996262
TI  - Men in nursing. Jobs for the boys.

PMID- 1996263
TI  - Men in nursing. Who flies highest?

PMID- 1996264
TI  - Men in nursing. A question of gender.

PMID- 1996265
TI  - That time of the month.

PMID- 1996266
TI  - Community. Dying with care. Care study.

PMID- 1996268
TI  - Strained relations.

PMID- 1996267
TI  - Babies in the blackout.

PMID- 1996269
TI  - Action on the environment. Anaesthetic agents.

PMID- 1996270
TI  - Prepare for PREPP. 5. Advance to go?

PMID- 1996271
TI  - Systems of life. The respiratory system. Part II.

PMID- 1996272
TI  - Continence. The Colley Model.

PMID- 1996273
TI  - Continence. Self-starters.

PMID- 1996274
TI  - Gulf War. The invisible wounds.

PMID- 1996275
TI  - Gulf War. Nursing support.

PMID- 1996276
TI  - Finding a path.

PMID- 1996278
TI  - The training shake-up.

PMID- 1996277
TI  - The changes.

PMID- 1996279
TI  - Expanding boundaries.

PMID- 1996280
TI  - Prepare for PREPP. 6. View from the top. Interview by Bernadette Friend.

PMID- 1996281
TI  - Prepare for PREPP. From the sharp end.

PMID- 1996282
TI  - Prepare for PREPP. Investing in the future.

PMID- 1996283
TI  - The facts about open learning.

PMID- 1996284
TI  - Open learning. Running an obstacle race. Interview by Laura Swaffield.

PMID- 1996285
TI  - Sharing the care.

PMID- 1996286
TI  - Communication skills. Progression to counselling.

PMID- 1996287
TI  - Journey through fear.

PMID- 1996288
TI  - Investigations into maternity services.

PMID- 1996289
TI  - MS prevalence among health-care workers.

PMID- 1996290
TI  - Perceptions of experiential learning.

PMID- 1996291
TI  - Protecting patients.

PMID- 1996292
TI  - Mental health. Seeing patients through.

PMID- 1996293
TI  - Computing in practice. Step by step.

PMID- 1996294
TI  - Computing in practice. Spreading the word.

PMID- 1996295
TI  - Computing in practice. Friend or foe?

PMID- 1996296
TI  - Answer please. Pantalar fracture dislocation of the talus with posterior
      displacement.

PMID- 1996297
TI  - Developing managers and leaders in orthopedics.

PMID- 1996298
TI  - Orthopedic surgery in Hungary.

PMID- 1996299
TI  - Weight bearing in Perthes' disease.
AB  - Results of two different types of treatment for 82 varus-derotation femur
      osteotomies to cure Perthes' disease are presented. Patients were treated between
      1974 and 1984. Postoperatively, in 30 cases weight bearing was allowed, while in
      52 cases, non-weight bearing braces were applied. Comparing the results of the
      two groups and considering the risk factors, the authors found that non-weight
      bearing does not influence end results after proximal femur osteotomy.

PMID- 1996300
TI  - Arthroplasty using acetabular implants in secondary protrusioned hips.
AB  - From 1979 to 1987, 102 operations were performed at the author's institution. The
      technique is simple and does not use any heterogenic material. There were no
      complications, except for one suppuration. Results are classified according to
      Charnley.

PMID- 1996301
TI  - Results of surgical treatment of knee instabilities.
AB  - Between January 1, 1981 and January 5, 1987, 146 reconstructive operations for
      acute (39) and chronic (107) knee instabilities were performed. THe majority of
      the acute cases were anteromedial (24), and of the chronic instabilities, 33 were
      anteromedial, 14 anterolateral, and 53 combined anteromedial-anterolateral. In
      terms of suture, replacement, and reinforcement of the damaged structures of the
      acute cases, 32 were good, 6 fair, and 1 poor, while the reconstruction,
      according to Muller, for chronic instabilities produced good results in 34, fair
      in 59, and poor in 14. It is essential that such operations be performed by a
      trained surgical team. For success, precise knowledge of anatomy, exact
      examination, accurate diagnosis, adequate surgical techniques, and careful
      postoperative treatment are essential.

PMID- 1996302
TI  - Surgical treatment of pathologic fractures from metastatic tumors of long bones.
AB  - Surgical treatment of 74 cases of impending and established metastatic pathologic
      fractures were analyzed. On the basis of various reports, the incidence of bone
      lesions, bone-seeking primary tumors, lesion sites, diagnostic techniques and
      possibilities, as well as indications for and methods of surgical treatment, are
      surveyed. Surgical intervention is only one aspect of the different components of
      general treatment in bone metastases. An aggressive surgical procedure yields
      very satisfactory results in most cases, compared with those of conservative
      treatment.

PMID- 1996303
TI  - Comparison of complications of total hip arthroplasty in rheumatoid arthritis,
      ankylosing spondylitis, and osteoarthritis.
AB  - Between 1971 and 1985, 3080 arthroplasties were performed. The authors analyze
      patients reoperated because of primary surgery complications. Of the primary
      arthroplasties (2889), there were 1788 operations performed for primary
      osteoarthritis, and 379 hip replacements for rheumatoid arthritis, ankylosing
      spondylitis, and systemic lupus erythematosus (SLE). Reoperation rates in both
      groups were the same (3.4%). In the group with rheumatoid arthritis, the rate was
      1.45%, much lower than the osteoarthritic group.

PMID- 1996304
TI  - Experimental stimulation of osteogenesis induced by bone matrix.
AB  - Bone gaps in 20 rabbits were filled with decalcified homologous bone. Direct
      currents, intravenous calcium, and anabolic steroids were administered for
      stimulation of osteogenesis. The shape and microscopic structure of the newly
      formed bone, together with the velocity of the osteogenesis, were investigated.
      Results were assessed by microscopic and radiographic analyses. In the group of
      calcium posttreatment, irregular shape and callosities were characteristic.
      Anabolic steroids failed to improve consolidation significantly; best results
      were seen after electrical stimulation of the grafted areas. In the group with
      electrical stimulation, fair shape, together with a more regular microscopic
      structure of the newly formed bone, were characteristic 4 weeks after surgery.
      Ungrafted gaps, together with defects filled with undecalcified cortical bone,
      failed to heal within the examined period of time.

PMID- 1996305
TI  - Results of ultrastructural analysis of the calf muscles in clubfoot.
AB  - Open biopsies were carried out on the muscles of 23 clubfoot patients, ages 9
      months to 4 years. Electron microscopic analyses of the so-called "clubfoot
      muscles" and the peroneal muscles were performed. The changes found were not
      present in every area of the muscles, but were surrounded by fields of normal
      structure. Fatty degeneration with fibrosis was observed as the consequence of
      immobilization. More marked loss was found in the contractile elements. The
      authors believe that neuromuscular atrophy is a primary cause of congenital
      clubfoot. The most seriously affected muscles in this study were the tibialis
      posterior and peroneal muscles. The material failed to prove correlation with
      age. Based on their observations, the authors suggest finishing all types of
      immobilization before 1 year of age, when children begin to walk.

PMID- 1996306
TI  - The effect of early anterior approach open reduction with functional
      postoperative treatment on the early development of the acetabulum in CDH.
AB  - Between 1980 and 1983, 30 anterior approach open reductions were performed on
      congenitally dislocated hips of 29 patients after unsuccessful conservative
      treatment; patients were between 6 and 18 months old. After the removal of the
      obstruction from the acetabulum, the reduction was performed with preservation of
      the limbus. Some part of the capsule was removed to constrict and tighten it and
      to prevent redislocation. This capsuloplasty demonstrates the success of a Pavlik
      harness and abduction splint postoperatively, without plaster fixation. The
      accelerated development of the acetabulum could be observed on radiograph by this
      functional treatment, compared to the control group treated with the usual hip
      spica postoperatively. The development of the acetabulum on the operated side
      almost equals the sound side within a year. If the operation was performed
      earlier, joint development would be quicker.

PMID- 1996307
TI  - Anterior shoulder subluxation in the throwing athlete.

PMID- 1996308
TI  - Thoracic disc prolapse in calcified discs.

PMID- 1996309
TI  - Activated protooncogenes in human lung tumors from smokers.
AB  - Fourteen primary human lung tumor DNAs from smokers were analyzed for
      transforming activity by two DNA transfection assays. Activated protooncogenes
      were detected in 3 of 11 tumor DNAs by the NIH 3T3 focus assay, whereas activated
      protooncogenes were detected in 11 of 13 tumor DNAs by the NIH 3T3 cotransfection
      nude mouse tumorigenicity assay. K- or NRAS genes activated by point mutation at
      codons 12 or 61 were detected in a large cell carcinoma, a squamous cell
      carcinoma, and 5 adenocarcinomas. An HRAS oncogene activated by a different
      mechanism was detected in an epidermoid carcinoma. One adenocarcinoma was found
      to contain an activated RAF gene. Two unidentified transforming genes were
      detected in a squamous cell carcinoma DNA and two adenocarcinoma DNAs. Eight of
      10 lung adenocarcinomas that had formed metastases at the time of surgery were
      found to contain RAS oncogenes. No significant increase in metastasis was
      observed in the lung adenocarcinomas that contained one or more 6-kilobase EcoRI
      alleles of the LMYC gene. Overall, 12 of 14 (86%) of the lung tumor DNAs from
      smokers were found to contain activated protooncogenes. RAS oncogenes appear to
      play a role in the development of metastases in lung adenocarcinomas.

PMID- 1996311
TI  - Identification of the intermediate allosteric species in human hemoglobin reveals
      a molecular code for cooperative switching.
AB  - The 10 ligation species of human cyanomethemoglobin were previously found to
      distribute into three discrete cooperative free energy levels according to a
      combinatorial code (i.e., dependent on both the number and configuration of
      ligated subunits). Analysis of this distribution showed that the hemoglobin
      tetramer occupies a third allosteric state in addition to those of the unligated
      (T) and fully ligated (R) species. To determine the nature of the intermediate
      allosteric state, we have studied the effects of pH, temperature, and single-site
      mutations on its free energy of quaternary assembly, in parallel with
      corresponding data on the deoxy (T) and fully ligated (R) species. Results
      indicate that the intermediate allosteric tetramer has the deoxy (T) quaternary
      structure. This finding, together with the resolved energetic distribution of the
      10 microstates reveals a symmetry rule for quaternary switching--i.e., switching
      from T to R occurs whenever a binding step creates a tetramer with one or more
      ligated subunits on each side of the alpha 1 beta 2 intersubunit contact. These
      studies also reveal significant cooperativity within each alpha 1 beta 1 dimer of
      the T-state tetramer. The ligand-induced tertiary free energy alters binding
      affinity within the T structure by 170-fold prior to quaternary switching.

PMID- 1996310
TI  - Borrowed proteins in bacterial bioluminescence.
AB  - A library of Photobacterium phosphoreum DNA was screened in lambda 2001 for the
      lumazine protein gene, using two degenerate 17-mer oligonucleotide probes that
      were deduced from a partial protein primary sequence. The lumazine protein gene
      was localized to a 3.4-kilobase BamHI/EcoRI fragment in one clone. The fragment
      contained an open reading frame, encoding a 189-residue protein, that had a
      predicted amino acid sequence that concurred with the partial sequence determined
      for lumazine protein. Considerable sequence similarity was detected between
      lumazine protein, the yellow fluorescence protein from Vibrio fischeri, and the
      alpha subunit of riboflavin synthetase (EC 2.5.1.9). A highly conserved sequence
      in lumazine protein corresponds to the proposed lumazine binding sites in the
      alpha subunit of riboflavin synthetase. Several secondary structure programs
      predict the conformation of this site in lumazine protein to be a beta-sheet. A
      minimal model with three interactions between the ligand and this beta-sheet
      structure is proposed, which is consistent with the results of NMR and ligand
      binding studies.

PMID- 1996312
TI  - Identification of a protein kinase multigene family of Dictyostelium discoideum:
      molecular cloning and expression of a cDNA encoding a developmentally regulated
      protein kinase.
AB  - We have identified protein kinase genes of Dictyostelium by using highly
      conserved amino acid sequence motifs to design the synthesis and amplification of
      DNA fragments by polymerase chain reactions (PCRs). Cloning and sequencing the
      PCR products have revealed five different members of the protein kinase multigene
      family. These five putative kinases showed varying degrees of amino acid sequence
      similarity (40-70%) to protein kinases in data bases and contained invariant
      amino acid residues characteristic of protein kinases. DNA from PCR was labeled
      and used to isolate several lambda gt11 cDNA clones, including one full-length
      one (Dd kinase-2). The nucleotide sequence of Dd kinase-2 contained a region
      identical to one of the cloned kinase fragments amplified by PCR, and based on
      the deduced amino acid sequence Dd kinase-2 encodes a protein of 479 amino acids.
      A 350-amino acid kinase domain at the C-terminal end shows high homology to the
      catalytic domains of protein kinase A, protein kinase C, S-6 kinase of Xenopus,
      and the suppressor of cdc25 of yeast. The N-terminal domain is highly basic and
      also contains alternating threonine/proline residues. The cDNA hybridized to a
      single copy gene but to two differentially regulated mRNAs--a 2.0-kilobase mRNA
      that is expressed in vegetative cells and a 2.2-kilobase mRNA that is expressed
      during development. The larger mRNA is induced by cAMP by using a cell-surface
      receptor-mediated signal transduction pathway.

PMID- 1996313
TI  - The frequency of meiotic recombination in yeast is independent of the number and
      position of homologous donor sequences: implications for chromosome pairing.
AB  - We constructed diploids of Saccharomyces cerevisiae homozygous for LEU2 and
      carrying one, two, or four copies of leu2 at ectopic locations and determined the
      frequency of 3+:1- (LEU2:leu2) meiotic tetrads. Gene conversion between a LEU2
      recipient and a leu2 ectopic donor occurred at the same frequency as did gene
      conversion between allelic copies of LEU2 and leu2. An increase in the number of
      possible ectopic donor loci did not lead to a proportional increase in the level
      of ectopic gene conversion. We suggest that the limiting step in meiotic
      recombination is the activation of a locus to become a recipient in recombination
      and that once activated, a locus can search the entire genome for a homologous
      partner with which to recombine. In this respect, this search for a homologous
      partner resembles the efficient premeiotic methylation/inactivation of duplicated
      sequences in Ascobolus and Neurospora. These observations support models in which
      strand exchange serves to align homologous chromosomes prior to their becoming
      much more fully synapsed by the elaboration of the synaptonemal complex.

PMID- 1996315
TI  - Evolution of life history variation among female mammals.
AB  - A unified approach is developed for the evolutionary structure of mammalian life
      histories; it blends together three basic components (individual growth or
      production rate as a function of body size, natural selection on age of maturity,
      and stable demography) to predict both the powers and the intercepts of the
      scaling allometry of life history variables to adult size. The theory also
      predicts the signs (+, -) of the correlations between life history variables when
      body size is held constant. Finally, the approach allows us to eliminate body
      size to predict the dimensionless relationships between the life history
      variables themselves.

PMID- 1996314
TI  - Evidence for an involvement of the brain cholecystokinin B receptor in anxiety.
AB  - The effect of neuropeptide cholecystokinin (CCK) receptor agonists and
      antagonists was examined in the rat elevated X-maze model of anxiety. The
      selective CCK-B receptor antagonists CI-988 (PD 134308) and L-365,260 produced
      anxiolytic-like effects, whereas MK-329, a CCK-A receptor antagonist, was
      respectively less potent by factors of 313 and 200. The intracerebroventricular
      administration of the nonselective CCK receptor agonist caerulein or the
      selective CCK-B receptor agonist pentagastrin increased dose dependently the
      level of anxiety. CI-988 dose dependently antagonized the anxiogenic response to
      pentagastrin but not that induced by pentylenetetrazol. These results strongly
      suggest that activation of the brain CCK-B receptor induces anxiety and that
      selective antagonists of this receptor represent a separate class of anxiolytic
      agents.

PMID- 1996316
TI  - An Escherichia coli tyrosine transfer RNA is a leucine-specific transfer RNA in
      the yeast Saccharomyces cerevisiae.
AB  - While the Escherichia coli Su-3 (tyrT) tyrosine tRNA suppressor inserts only
      tyrosine at amber codons in E. coli, we show here that in Saccharomyces
      cerevisiae this tRNA inserts leucine and no significant amounts of any other
      amino acid. Thus, the E. coli tyrosine tRNA is functionally a leucine tRNA in
      yeast cytoplasm. This functional identity may correlate with a structural
      relationship between the E. coli tyrosine and yeast leucine tRNAs, which are both
      members of the uncommon type II class of tRNA structures. The results raise the
      possibility that in evolution a tRNA may be more closely related to a tRNA of
      different acceptor specificity, but of the same type class, than to one with the
      same amino acid specificity, but of a different type class.

PMID- 1996317
TI  - Inducible proteins binding to the murine thymidine kinase promoter in late G1/S
      phase.
AB  - By performing DNase I footprint and band-shift analyses of a 170-base-pair region
      of the murine thymidine kinase promoter, we identified an inducible DNA binding
      activity that we named Yi. Yi binding activity was not detected in G0 and G1
      extracts, but it was observed as cells crossed the G1/S boundary. Yi proteins
      bind specifically to a consensus sequence (CCCNCNNNCT) found at three distinct
      sites in this promoter region. We also observed a murine Sp1 binding activity
      that was constitutive throughout the cell cycle. We propose that the G1/S
      specific Yi binding is important for murine thymidine kinase gene regulation and
      perhaps also for initiation of DNA synthesis.

PMID- 1996319
TI  - Cotranslational autoproteolysis involved in gene expression from a double
      stranded RNA genetic element associated with hypovirulence of the chestnut blight
      fungus.
AB  - The genetic information responsible for reduced virulence (hypovirulence) of the
      chestnut blight fungus Cryphonectria parasitica is thought to reside on
      cytoplasmically replicating double-stranded RNA (dsRNA) molecules. Cell-free
      translation of synthetic transcripts corresponding to the 5'-terminal 2640
      nucleotides of the sense strand of the large dsRNA present in C. parasitica
      hypovirulent strain EP713 yielded two polypeptides with apparent molecular masses
      of 29 and 40 kDa. Nucleotide sequence analysis indicated that p29 and p40 were
      encoded by a single large open reading frame. The coding regions for p29 and p40
      were mapped to nonoverlapping portions of the 5'- and 3'-terminal domains of the
      open reading frame, respectively. Kinetic analysis and in vitro translation
      studies with chimeric transcripts indicated that p29 is autocatalytically
      released from a nascent polyprotein during translation. Microsequence analysis of
      the amino terminus of radiolabeled p40 indicated that cleavage occurred between
      Gly-248 and Gly-249, consistent with translational mapping analysis. Examination
      of the p29 amino acid sequence revealed similarity to the Potyvirus-encoded
      cysteine-type proteinase HC-Pro. These results indicate the types of mechanism
      that operate during gene expression by hypovirulence-associated dsRNA genetic
      elements.

PMID- 1996318
TI  - The v-src inducible gene 9E3/pCEF4 is regulated by both its promoter upstream
      sequence and its 3' untranslated region.
AB  - The 9E3/pCEF4 mRNA is strongly induced in Rous sarcoma virus-transformed chicken
      embryo fibroblasts when compared to untransformed cells. To identify cis-acting
      transcriptional elements that confer inducibility by v-src, we isolated the 9E3
      promoter upstream region. We found that 1.53 kilobases upstream of the
      transcriptional start site, when placed in front of a reporter gene, conferred a
      small degree of inducibility by v-src, in both transient and stable
      transfections. Two potential AP-1 sites were identified in the 9E3 promoter. AP-1
      elements have been implicated previously in mediating a transcriptional response
      to v-src in fibroblast cell lines. These elements alone do not confer a
      significant inducibility by v-src in primary chicken embryo fibroblasts. Since
      the 9E3 mRNA is stabilized in transformed cells, we replaced the 3' untranslated
      region of the reporter gene with the 9E3 3' untranslated region and found this
      construct to be strongly responsive to stimulation by v-src. In addition, the 9E3
      3' untranslated region increased the response to serum and the tumor promoter
      phorbol 12-myristate 13-acetate. This suggests that a posttranscriptional
      mechanism plays a major role in the induction of 9E3 expression.

PMID- 1996320
TI  - Selective inhibition by a synthetic hirudin peptide of fibrin-dependent
      thrombosis in baboons.
AB  - To determine the importance of the thrombin substrate recognition exosite for
      fibrinogen binding in the formation of both arterial and venous thrombi, we
      evaluated the antithrombotic effects of the tyrosine-sulfated dodecapeptide from
      residues 53-64 of hirudin (H peptide) in a nonhuman primate model. This peptide
      was studied because it inhibits thrombin cleavages of fibrinogen by simple
      competition without blocking enzyme catalytic-site function. When an exteriorized
      arteriovenous access shunt model was used in baboons (Papio anubis), thrombus
      formation was induced by placing a thrombogenic device made of (i) a segment of
      tubing coated covalently with type I collagen, which generated platelet-rich
      thrombi under arterial flow conditions, and (ii) two subsequent annular regions
      of flow expansion that produced fibrin-rich thrombi typically associated with
      venous valves and veins. Thrombus formation was quantified by measurements of
      111In-labeled platelet and 125I-labeled fibrinogen deposition in both arterial
      flow and venous-flow portions of the device. Continuous infusion of H peptide
      (0.5, 15, and 75 mg/kg) proximal to the device for 40 min interrupted, in a dose
      response fashion, formation of fibrin-rich thrombus in the regions of disturbed
      flow and generation of fibrinopeptide A. In contrast, H peptide did not inhibit
      the capacity of platelets to deposit on the collagen surface (P greater than 0.2
      at all doses) or to form hemostatic plugs (as assessed by measurements of
      bleeding time; P greater than 0.1 at all doses). These findings suggest that, by
      competitive inhibition of fibrinogen binding to thrombin, fibrin-rich venous-type
      thrombus formation may be selectively prevented. This strategy may be
      therapeutically attractive for preserving normal platelet function when
      conventional anticoagulant therapy is contraindicated.

PMID- 1996321
TI  - Sexual transmission of human T-cell leukemia virus type I associated with the
      presence of anti-Tax antibody.
AB  - The tax gene product (Tax protein) of human T-cell leukemia virus type I (HTLV-I)
      is a specific transcriptional activator of the viral long terminal repeat
      sequence and is essential for the replication cycle of the virus. To elucidate
      the relationship between the presence of anti-Tax antibody and the transmission
      of the viral infection, annual consecutive serum samples from married couples
      serologically discordant or concordant for HTLV-I were examined. These included 5
      individuals whose spouses seroconverted during this 5-year follow-up study
      period. The samples were tested by a Western blot assay using a recombinant Tax
      protein as the antigen. The results showed that 24 of 32 (75%) men in the
      concordant couples (both husband and wife were HTLV-I carriers) had anti-Tax
      antibody, while only 5 of 18 (27.8%) men in the discordant couples (husband was
      carrier and wife was seronegative to HTLV-I) were positive for anti-Tax antibody
      (P = 0.0012). Furthermore, all spouses of the 5 seroconverters (4 women and 1
      man) had anti-Tax antibody, while only 23 of 46 (50%) age-matched randomly
      selected HTLV-I carriers from the discordant-couple group had anti-Tax antibody.
      When the data were analyzed by gender, all husbands of the female seroconverters
      had anti-Tax antibodies, which was significantly higher than the prevalence of
      anti-Tax antibodies in men who did not transmit the virus to their spouses during
      the follow-up period (P = 0.017). In addition, antibody reactivity to other HTLV
      I antigens (including Env gp46, transmembrane protein gp21, and Gag p19 and p24)
      were examined. The results indicated no significant differences between the
      prevalence of antibody reactivity to any of the antigens in the spouses of the
      seroconverters and the reference group. We conclude that the presence of anti-Tax
      antibody in men may indicate a high risk of viral transmission to their wives via
      heterosexual routes.

PMID- 1996322
TI  - Multilocus genetic structure of ancestral Spanish and colonial Californian
      populations of Avena barbata.
AB  - We have applied a multivariate log-linear technique to the analysis of interlocus
      allelic associations among 14 allozyme loci in a sample of 4011 plants from 42
      Spanish populations of Avena barbata. The loci fell into three natural groups of
      five, five, and four loci. The five loci of the first group are invariant, or
      nearly so, throughout the range of the species. The genetic organization of the
      loci of this set is defined by a single five-locus genotype; each allele of this
      predominant genotype is a "wild-type" allele that contributes favorably to
      adaptedness in all single-locus and multilocus configurations regardless of
      environment. Although allelic diversity is high in Spain for the nine loci of the
      second and third sets, log-linear analyses showed that these loci are tied
      together in Spanish populations through complex networks of overlapping lower
      order interlocus interactions. The ancestral Spanish and colonial Californian
      gene pools are closely similar in allelic composition on a locus-by-locus basis;
      however, Spanish allelic configurations at two-locus and higher-order levels are
      usually different from and much less tightly organized than in Californian
      populations. We conclude that the major force involved in the evolution of the
      colonial populations was selection that led to reorganization, at the interlocus
      level, of the ancestral Spanish allelic ingredients into different multilocus
      genotypes adapted to Californian habitats.

PMID- 1996323
TI  - Genetic diversity and adaptedness in tetraploid Avena barbata and its diploid
      ancestors Avena hirtula and Avena wiestii.
AB  - Avena barbata, a tetraploid grass, is much more widely adapted and successful in
      forming dense stands than its diploid ancestors. The success of such polyploids
      has often been attributed to heterosis associated with ability to breed true for
      a highly heterozygous state in which allelic differences between the parents are
      fixed in the polyploid by chromosome doubling. We have examined the relationship
      between genetic diversity and adaptedness for 14 allozyme loci in A. barbata and
      its diploid ancestors in samples collected from diverse habitats in Israel and
      Spain. The relationship varied from locus to locus: superior adaptedness was
      associated with genetic uniformity for five loci, in part with genetic uniformity
      and in part with genetic diversity (monomorphism for a single heteroallelic
      quadriplex) for one locus, and with allelic diversity in the form of
      heteroallelic quadriplexes combined with genotypic diversity in the form of
      complex polymorphisms among different homoallelic and/or heteroallelic
      quadriplexes for the eight remaining loci. These results indicate that allelic
      diversity fixed in nonsegregating form through chromosome doubling was an
      important factor in the evolution of adaptedness in A. barbata. However, it is
      unlikely that heterosis associated with heterozygosity contributed significantly
      to superior adaptedness in either the diploids or the tetraploid because
      virtually all loci (approximately 99%) were homozygous in the Avena diploids and
      tetraploid.

PMID- 1996324
TI  - Interleukin 2 induces tyrosine phosphorylation and activation of p72-74 Raf-1
      kinase in a T-cell line.
AB  - Interleukin 2 (IL-2) is a lymphokine, produced by T cells upon antigenic or
      mitogenic stimulation, that is a critical regulator of T-cell proliferation.
      Although the binding of IL-2 to its receptor has been well characterized, the
      molecular mechanisms by which IL-2 transmits its signal from the membrane to the
      interior of the cell are poorly understood. Like most other growth factors, IL-2
      causes rapid phosphorylation of proteins within its target cells. Unlike many
      other growth factors, however, the known subunits of the IL-2 receptor lack
      tyrosine-specific kinase activity, and little is known about the kinases whose
      activities are regulated by IL-2. Here we show that IL-2 (but not IL-4) induces
      rapid phosphorylation of the p72-74 serine/threonine-specific kinase encoded by
      the c-Raf-1 protooncogene in an IL-2-dependent murine T-cell line, CTLL-2, and
      that this phosphorylation is associated with increased kinase activity in p72-74
      Raf-1-containing immune complexes. The concentration dependence of IL-2-mediated
      elevations in Raf-1 kinase activity correlated well with IL-2-stimulated
      proliferation of CTLL-2 cells. Furthermore, much of the IL-2-stimulated
      phosphorylation of p72-74 Raf-1 occurred on tyrosines. To our knowledge, the Raf
      1 kinase represents the first endogenous substrate of an IL-2-regulated tyrosine
      kinase to be identified.

PMID- 1996325
TI  - Protein solution structure determination using distances from two-dimensional
      nuclear Overhauser effect experiments: effect of approximations on the accuracy
      of derived structures.
AB  - Solution structures for many proteins have been determined to date utilizing
      interproton distance constraints estimated from two-dimensional nuclear
      Overhauser effect (2D NOE) spectra. Although the simple isolated spin pair
      approximation (ISPA) generally used can result in systematic errors in distances,
      the large number of constraints enables protein structure to be defined with
      reasonably high resolution. Effects of these systematic errors on the resulting
      protein structure are examined. Iterative relaxation matrix calculations, which
      account for dipolar interactions between all protons in a molecule, can
      accurately determine internuclear distances with little or no a priori knowledge
      of the molecular structure. The value of this additional complexity is also
      addressed. To assess these distance determination methods, hypothetical
      "experimental" data, including random noise and peak overlap, are calculated for
      an arbitrary "true" protein structure. Three methods of obtaining distance
      constraints from 2D NOE peak intensities are examined: one entails a conservative
      use of ISPA, one assumes the ISPA to be fairly accurate, and one utilizes an
      iterative relaxation matrix method called MARDIGRAS (matrix analysis of
      relaxation for discerning the geometry of an aqueous structure), developed in
      this laboratory. A distance geometry algorithm was used to generate a family of
      structures for each distance set. The quality of the average structure from each
      family was good. The root-mean-square deviation of that average structure from
      the true structure was improved about 2-5% using the more restrictive rather than
      the more conservative ISPA approach. Use of MARDIGRAS in a conservative fashion-
      i.e., with a poor initial model--resulted in improvement in the root-mean-square
      deviation by 8-15%. With a better initial model, MARDIGRAS obtained even more
      accurate distances. MARDIGRAS also permits analysis of 2D NOE data at longer
      mixing times, yielding additional distances. Use of more restrictive ISPA
      distances did, however, result in a few systematically incorrect structural
      features in local regions of the protein, producing distortions of 2-3 A.
      Comparison between experimental data and spectra calculated for the structures
      correlates with root-mean-square deviation, offering a method of structure
      evaluation. An R factor for evaluating fit between experimental and calculated 2D
      NOE intensities is proposed.

PMID- 1996326
TI  - Seismic communication in a blind subterranean mammal: a major somatosensory
      mechanism in adaptive evolution underground.
AB  - Seismic communication, through low-frequency and patterned substrate-borne
      vibrations that are generated by head thumping, and which travel long distances
      underground, is important in the nonvisual communication of subterranean mole
      rats of the Spalax ehrenbergi superspecies (2n = 52, 54, 58, and 60) in Israel.
      This importance pertains both intraspecifically in adaptation and
      interspecifically in speciation. Neurophysiologic, behavioral, and anatomic
      findings in this study suggest that the mechanism of long-distance seismic
      communication is basically somatosensory and is independent of the auditory
      mechanism. Seismic communication thus appears to be a channel of communication
      important in the evolution of subterranean mammals that display major adaptation
      to life underground.

PMID- 1996327
TI  - In vivo mapping of a sequence required for interference with the yeast killer
      virus.
AB  - The Saccharomyces cerevisiae viruses are noninfectious double-stranded RNA
      viruses whose segments are separately encapsidated. A large viral double-stranded
      RNA (L1; 4580 base pairs) encodes all required viral functions. M1, a double
      stranded RNA of 1.9 kilobases, encodes an extracellular toxin (killer toxin) and
      cellular immunity to that toxin. Some strains contain smaller, S, double-stranded
      RNAs, derived from M1 by internal deletion. Particles containing these defective
      interfering RNAs can displace M1 particles by faster replication and thus convert
      the host strain to a nonkiller phenotype. In this work, we report the development
      of an assay in which the expression of S plus-strand from an inducible plasmid
      causes the loss of M1 particles. This assay provides a convenient method for
      identifying in vivo cis-acting sequences important in viral replication and
      packaging. We have mapped the sequence involved in interference to a region of
      132 base pairs that includes two sequences similar to the viral binding site
      sequence previously identified in L1 by in vitro experiments.

PMID- 1996328
TI  - Dystrophin is transcribed in brain from a distant upstream promoter.
AB  - Dystrophin, the protein product of the Duchenne muscular dystrophy gene, is
      expressed in brain as well as muscle. The role of dystrophin in the brain is not
      clear, though one-third of Duchenne muscular dystrophy patients exhibit some
      degree of mental retardation. We have isolated the genomic region encoding the
      alternative 5' terminus of dystrophin used in the brain. Primer extension and
      polymerase chain reaction assays on RNA demonstrate that this region contains an
      alternative promoter for dystrophin used in the brain. Physical mapping of this
      region indicates that this brain promoter is located greater than 90 kilobases 5'
      to the promoter used in muscle and 400 kilobases from exon 2 to which it is
      spliced. The large physical distance between the promoters, taken together with
      their known tissue selectivities, suggests that in certain patients a deletion of
      either dystrophin promoter might give rise to reduced dystrophin expression
      selective to brain or muscle. We have identified one such individual with
      specific deletion of the dystrophin muscle promoter, giving rise to Becker
      muscular dystrophy, and we predict that specific loss of the brain promoter may
      be one cause of X chromosome-linked mental retardation.

PMID- 1996329
TI  - The role of the superior colliculus in facilitating visual attention and form
      perception.
AB  - When interhemispheric transfer in cats is studied from an intact hemisphere to a
      hemisphere with a suprasylvian cortical lesion, excellent transfer of grating
      discriminations, but no transfer of forms, is present. Stimuli with global,
      repetitive features covering a large visual field (gratings), which can be
      discriminated by preattentive vision, are transferred; perception of stimuli with
      local features (forms), which require serial exploration using focal vision, is
      defective in the hemisphere with cortical lesion and transfer is lacking.
      Influence of the midbrain in facilitating focal vision is shown by the
      restoration of form discriminations after section of the superior collicular
      commissure. It is hypothesized that the perceptual defect after lesion in the
      suprasylvian cortex is due to poor spatial attention and its restoration after
      midbrain lesion is due to improved function of those collicular cells that
      mediate orienting of attention.

PMID- 1996330
TI  - Mechanism of glucoregulatory responses to stress and their deficiency in
      diabetes.
AB  - During exercise, increased energy demands are met by increased glucose production
      that occurs simultaneously with the increased glucose uptake. We had previously
      observed that, during exercise, metabolic clearance rate of glucose (MCR)
      increases markedly in normal, but only marginally in poorly controlled diabetic
      dogs. We wished to determine (i) whether in a more general model of stress
      matched increases in rate of appearance of glucose and MCR also occur, or if MCR
      is suppressed, as during catecholamine infusion; and (ii) whether diabetes
      affects stress-induced changes in rate of glucose appearance and MCR. Therefore,
      we injected carbachol (27 nmol/50 microliters), an analog of acetylcholine,
      intracerebroventricularly in seven conscious dogs before and after induction of
      alloxan diabetes. In normal dogs, plasma epinephrine and cortisol increased 4- to
      5-fold, whereas norepinephrine and glucagon doubled. Plasma insulin, however,
      remained unchanged. Tracer-determined hepatic glucose production increased
      rapidly, but transiently, by 2.5-fold. This increment can be fully explained by
      the observed increments in the counterregulatory hormones. Surprisingly, however,
      MCR also promptly increased, and therefore, plasma glucose changed only
      marginally. After induction of diabetes, the animals were given
      intracerebroventricular carbachol while plasma glucose was maintained at moderate
      hyperglycemia (9.0 +/- 0.4 mM). Increments in counterregulatory hormones were
      similar to those seen in normal dogs, except for exaggerated norepinephrine
      release. Peripheral insulin levels were higher in diabetic than in normal dogs;
      however, MCR was markedly reduced and the lipolytic response to stress increased,
      indicating insulin resistance. Interestingly, the hyperglycemic response to
      stress was 6-fold greater in diabetic than normal animals, relating mainly to the
      failure of MCR to rise. Plasma lactate increased equivalently in diabetic and
      normal animals despite suppression of MCR in the diabetics, indicating either
      greater muscle glycogenolysis and/or impairment in glucose oxidation. We conclude
      that in this stress model MCR increases as in exercise in normal but not in
      diabetic dogs. We speculate that glucose uptake in stress could be mediated
      through an insulin-dependent neural mechanism.

PMID- 1996331
TI  - Phased cis-acting promoter elements interact at short distances to direct avian
      skeletal alpha-actin gene transcription.
AB  - Recently, site-directed mutagenesis uncovered four positive cis-acting elements
      in the 5' promoter region of the chicken skeletal alpha-actin gene that directs
      myogenic tissue-restricted expression. In this study, interactions between the
      four promoter sites were examined by means of a series of insertion mutations
      that increased the linker region between adjacent elements by roughly half or
      complete DNA helical turns. Unexpectedly, transcriptional activity for all three
      sets of linker mutants, as assayed with a chloramphenicol acetyltransferase
      reporter gene, was found to vary in a fashion resembling a damped sinusoid with a
      period of roughly 10 base pairs, where the sinusoidal maxima appeared when length
      was increased by half-integral number of helix turns. We present a model which
      states that in the undistorted wild-type 5' flanking sequence, linker domains
      position each of the four promoter sites on the helix face opposite that of its
      immediate neighbors; when any of the three linkers is increased by approximately
      a half-integral number of helix turns, pairs of neighboring promoter sites are
      brought into alignment. We propose that this is the required orientation for
      inducing skeletal muscle-specific promoter activity, achieved in the wild-type
      promoter as a result of protein-induced torsional deformation.

PMID- 1996332
TI  - Clustered tRNA genes in Schizosaccharomyces pombe centromeric DNA sequence
      repeats.
AB  - The centromere-associated B' and B DNA sequence repeats of Schizosaccharomyces
      pombe chromosomes I and II have been found to contain clusters of tRNA genes. The
      centromere II region (cen2) includes at least 22 tRNA genes distributed among
      five copies of the B sequence repeat containing genes specifying tRNA(Ile),
      tRNA(Ala), and tRNA(Val). Individual B repeats are variously associated with
      other tRNA genes, including those specifying tRNA(Lys), tRNA(Arg), and
      tRNA(Glu2). The centromere I region (cen1) contains at least six tRNA genes in
      two copies of the B' repeated element, including genes specifying tRNA(Ile),
      tRNA(Ala), and tRNA(Glu3). Multiple tandemly arranged clusters of tRNA genes are
      presumably conserved due to restricted recombination frequencies in the
      centromere regions.

PMID- 1996333
TI  - Atypical prodynorphin gene expression in corticosteroid-producing cells of the
      rat adrenal gland.
AB  - Prodynorphin (proDyn) gene expression was examined in the rat adrenal gland. In
      situ hybridization revealed a heterogenous proDyn mRNA distribution limited
      almost exclusively to the adrenal cortex; the inner cortical layers contained the
      highest amounts. In the adrenal medulla, only scattered single cells were seen.
      By Northern (RNA) blot analysis, adrenocortical proDyn mRNA levels were highly
      abundant but of smaller size than proDyn transcripts found in the brain. Low
      levels of the brain-size proDyn mRNA transcript were detected but restricted to
      the medulla. A discrepancy was suggested when comparing the high abundance of
      proDyn mRNA levels with the low levels of proDyn-derived peptide in the adrenal.
      A hypothesis of nontranslation of the shorter proDyn mRNA by adrenocortical cells
      was rejected because polysomal loading analysis suggests that the mRNA is
      translated. We propose that adrenocortical proDyn-derived peptides are not
      targeted for storage but are released shortly after synthesis, thus accounting
      for low peptide levels. We also measured proDyn mRNA levels in response to
      stimuli known to affect adrenocortical cells and their most important function-
      steroidogenesis. Adrenals from hypophysectomized rats had less proDyn mRNA by a
      factor of 5 than adrenals from normal sham-operated rats. Normal levels were
      restored by adrenocorticotrophic hormone administration, indicating a potential
      importance of adrenal proDyn in the hypothalamic-adrenal-pituitary axis.

PMID- 1996334
TI  - In vitro peptide binding to the heavy chain of the class I molecule of the major
      histocompatibility complex molecule HLA-A2.
AB  - The heavy chain of class I molecules of the major histocompatibility complex
      forms the binding site for antigenic peptides. We describe the binding of a
      synthetic peptide to the purified heavy chain of the human major
      histocompatibility complex molecule HLA-A2. The peptide binding capacity is found
      to be markedly increased if the protein is first partly denatured by reduction of
      its disulfide bonds in detergent and subsequently renatured by reoxidation. In
      the presence of certain detergents, the heavy chain binds peptides even when the
      protein is partly unfolded.

PMID- 1996336
TI  - Chicken major histocompatibility complex-encoded B-G antigens are found on many
      cell types that are important for the immune system.
AB  - B-G antigens are a polymorphic multigene family of cell surface molecules encoded
      by the chicken major histocompatibility complex (MHC). They have previously been
      described only on cells of the erythroid lineage. By using flow cytometry,
      section staining, and immunoprecipitation with monoclonal antibodies and rabbit
      antisera to B-G molecules and by using Northern blots with B-G cDNA clones, we
      demonstrate here that B-G molecules and RNA are present in many other cell types:
      thrombocytes, peripheral B and T lymphocytes, bursal B cells and thymocytes, and
      stromal cells in the bursa, thymus, and caecal tonsil of the intestine. The
      reactions also identify at least one polymorphic B-G determinant encoded by the B
      F/B-L region of the chicken MHC. The serology and tissue distribution of B-G
      molecules are as complex as those of mammalian MHC class I and class II
      molecules. These facts, taken with certain functional data, lead us to suggest
      that B-G molecules have an important role in the selection of B cells in the
      chicken bursa.

PMID- 1996335
TI  - Nucleosomes on linear duplex DNA allow homologous pairing but prevent strand
      exchange promoted by RecA protein.
AB  - To understand the molecular basis of gene targeting, we have studied interactions
      of nucleoprotein filaments comprised of single-stranded DNA and RecA protein with
      chromatin templates reconstituted from linear duplex DNA and histones. We
      observed that for the chromatin templates with histone/DNA mass ratios of 0.8 and
      1.6, the efficiency of homologous pairing was indistinguishable from that of
      naked duplex DNA but strand exchange was repressed. In contrast, the chromatin
      templates with a histone/DNA mass ratio of 9.0 supported neither homologous
      pairing nor strand exchange. The addition of histone H1, in stoichiometric
      amounts, to chromatin templates quells homologous pairing. The pairing of
      chromatin templates with nucleoprotein filaments of RecA protein-single-stranded
      DNA proceeded without the production of detectable networks of DNA, suggesting
      that coaggregates are unlikely to be the intermediates in homologous pairing. The
      application of these observations to strategies for gene targeting and their
      implications for models of genetic recombination are discussed.

PMID- 1996337
TI  - Characterization of lipid domains in erythrocyte membranes.
AB  - Fluorescence digital imaging microscopy was used to study the lateral
      distribution of the lipid components in erythrocyte membranes. Intact
      erythrocytes labeled with phospholipids containing a fluorophore attached to one
      fatty acid chain showed an uneven distribution of the phospholipids in the
      membrane thereby demonstrating the presence of membrane domains. The enrichment
      of the lipotropic compound chlor-promazine in domains in intact erythrocytes also
      suggested that the domains are lipid-enriched regions. Similar membrane domains
      were present in erythrocyte ghosts. The phospholipid enrichment was increased in
      the domains by inducing membrane protein aggregation. Double-labeling experiments
      were done to determine the relative distributions of different phospholipids in
      the membrane. Vesicles made from extracted lipids did not show the presence of
      domains consistent with the conclusion that membrane proteins were responsible
      for creating the domains. Overall, it was found that large domains exist in the
      red blood cell membrane with unequal enrichment of the different phospholipid
      species.

PMID- 1996338
TI  - In vivo mapping of a DNA adduct at nucleotide resolution: detection of pyrimidine
      (6-4) pyrimidone photoproducts by ligation-mediated polymerase chain reaction.
AB  - DNA adducts in unique sequences along the mammalian genome are mapped in vivo at
      single-nucleotide resolution. Pyrimidine (6-4) pyrimidone photoproducts [(6-4)
      photoproducts] represent one of the two major adduct classes found after UV
      irradiation of DNA and were shown to play an important role in UV-induced
      mutagenesis. After UV light treatment of cells, DNA is prepared and chemically
      cleaved at (6-4) photoproducts with piperidine. Gene-specific fragments are then
      amplified from total genomic DNA by use of a ligation-mediated polymerase chain
      reaction. Analysis of the human chromosome X-linked phosphoglycerate kinase
      (PGK1) gene's promoter has shown that the frequency of (6-4) photoproducts
      expressed as piperidine-labile sites is (i) high at TpC and CpC dinucleotides,
      (ii) dependent on the nearest-neighbor bases, (iii) inhibited by the binding of a
      transcription factor, and (iv) different for DNA derived from the active and
      inactive X chromosome. This latter difference is mainly a consequence of the
      presence of 5-methylcytosine (m5C) in CpG dinucleotides on the inactive X
      chromosome. 5-Methylcytosine in the sequences Tm5CG and Cm5CG inhibits the
      formation of (6-4) photoproducts. Thus, in addition to in vivo mapping of a DNA
      adduct at nucleotide resolution, we also report another method for methylation
      analysis and photofootprinting.

PMID- 1996339
TI  - Iteron inhibition of plasmid RK2 replication in vitro: evidence for
      intermolecular coupling of replication origins as a mechanism for RK2 replication
      control.
AB  - The broad-host-range plasmid RK2 and its derivatives are maintained in Gram
      negative bacteria at a specific copy number that appears to be determined by a
      series of direct repeats (iterons) located at the RK2 replication origin and by
      the RK2 replication initiation protein. TrfA. An in vitro replication system was
      developed from Escherichia coli that is active with either the intact eight
      iteron RK2 origin or a minimal five-iteron RK2 origin when purified TrfA protein
      is provided. Using this in vitro replication system, we have examined the
      mechanism(s) of copy-number control. It was found that two or more RK2 iterons
      present on a supercoiled compatible plasmid molecule are capable of specifically
      inhibiting in vitro the replication of either functional RK2 origin plasmid and
      that this inhibition is not overcome by adding increasing amounts of TrfA
      protein. A mutant TrfA protein, TrfA-33(cop254D), that increases the copy number
      of an RK2 origin in vivo exhibits replication kinetics and activity levels in
      this in vitro system similar to that of the wild-type protein. However, RK2 in
      vitro replication initiated by TrfA-33(cop254D) has a much reduced sensitivity to
      iteron inhibition. These data support a model for RK2 copy-number control that
      involves intermolecular coupling between TrfA-bound iterons.

PMID- 1996340
TI  - scid mutation in mice confers hypersensitivity to ionizing radiation and a
      deficiency in DNA double-strand break repair.
AB  - C.B-17 severe combined immunodeficient (scid) mice carry the scid mutation and
      are severely deficient in both T cell- and B cell-mediated immunity, apparently
      as a result of defective V(D)J joining of the immunoglobulin and T-cell receptor
      gene elements. In the present studies, we have defined the tissue, cellular, and
      molecular basis of another characteristic of these mice: their hypersensitivity
      to ionizing radiation. Bone marrow stem cells, intestinal crypt cells, and
      epithelial skin cells from scid mice are 2- to 3-fold more sensitive when
      irradiated in situ than are congenic BALB/c or C.B-17 controls. Two independently
      isolated embryo fibroblastic scid mouse cell lines display similar
      hypersensitivities to gamma-rays. In addition, these cell lines are sensitive to
      cell killing by bleomycin, which also produces DNA strand breaks, but not by the
      DNA crosslinking agent mitomycin C or UV irradiation. Measurement of the
      rejoining of gamma-ray-induced DNA double-strand breaks by pulsed-field gel
      electrophoresis indicates that these animals are defective in this repair system.
      This suggests that the gamma-ray sensitivity of the scid mouse fibroblasts could
      be the result of reduced repair of DNA double-strand breaks. Therefore, a common
      factor may participate in both the repair of DNA double-strand breaks as well as
      V(D)J rejoining during lymphocyte development. This murine autosomal recessive
      mutation should prove extremely useful in fundamental studies of radiation
      induced DNA damage and repair.

PMID- 1996341
TI  - Identification of the ancestral haplotype for apolipoprotein B suggests an
      African origin of Homo sapiens sapiens and traces their subsequent migration to
      Europe and the Pacific.
AB  - The probable ancestral haplotype for human apolipoprotein B (apoB) has been
      identified through immunological analysis of chimpanzee and gorilla serum and
      sequence analysis of their DNA. Moreover, the frequency of this ancestral apoB
      haplotype among different human populations provides strong support for the
      African origin of Homo sapiens sapiens and their subsequent migration from Africa
      to Europe and to the Pacific. The approach used here for the identification of
      the ancestral human apoB haplotype is likely to be applicable to many other
      genes.

PMID- 1996342
TI  - Tissue acylation by the chlorofluorocarbon substitute 2,2-dichloro-1,1,1
      trifluoroethane.
AB  - Hydrochlorofluorocarbons (HCFCs) are being developed as substitutes for ozone
      depleting chlorofluorocarbons (CFCs); because widespread human exposure to HCFCs
      may be expected, it is important to evaluate their toxicities thoroughly. Here we
      report studies on the bioactivation of the CFC substitute 2,2-dichloro-1,1,1
      trifluoroethane (HCFC-123) to an electrophilic intermediate that reacts
      covalently with liver proteins. HCFC-123 and its analog halothane (2-bromo-2
      chloro-1,1,1-trifluoroethane) were studied in rats by 19F NMR spectroscopy, and
      we found that a trifluoroacetylated lysine adduct was formed with liver proteins.
      Also, the pattern of proteins immunoreactive with hapten-specific anti
      trifluoroacetylprotein antibodies was identical in livers of HCFC-123- and
      halothane-exposed rats. Because halothane causes an idiosyncratic, and sometimes
      fatal, hepatitis that is associated with an immune response against several
      trifluoroacetylated liver proteins, the present findings raise the possibility
      that humans exposed to HCFC-123 or structurally related HCFCs may be at risk of
      developing an immunologically mediated hepatitis.

PMID- 1996343
TI  - Chromostatin, a 20-amino acid peptide derived from chromogranin A, inhibits
      chromaffin cell secretion.
AB  - Chromogranin A (CGA) is a ubiquitous 48-kDa secretory protein present in adrenal
      medulla, anterior pituitary, central and peripheral nervous system, endocrine
      gut, thyroid, parathyroid, and endocrine pancreas. Recently, we have demonstrated
      that the protein could be a precursor of bioactive peptides capable of modulating
      catecholamine secretion from cultured adrenal medullary chromaffin cells. Here we
      cleaved CGA purified from bovine chromaffin granules with endoproteinase Lys-C,
      and we isolated and partially sequenced the peptide inhibiting catecholamine
      secretion from cultured chromaffin cells. A corresponding synthetic peptide
      composed of the first 20 N-terminal amino acids produced a dose-dependent
      inhibition in the 10(-9) to 10(-6) M range (with an ID50 of 5 nM) of the
      catecholamine secretion evoked by carbamoylcholine or by potassium at a
      depolarizing concentration. This peptide affected secretagogue-induced calcium
      fluxes but did not alter sodium fluxes. It was found to increase desensitization
      of cell responses and to modify the kinetics of catecholamine release. Our
      results indicate that the peptide is extracellularly generated from CGA by a
      calcium-dependent proteolytic mechanism. We suggest that this peptide, named
      chromostatin, may be an endocrine modulator of catecholamine-associated
      responses.

PMID- 1996344
TI  - Characterization of a variant of human T-lymphotropic virus type I isolated from
      a healthy member of a remote, recently contacted group in Papua New Guinea.
AB  - We report the characterization of a variant of human T-lymphotropic virus type I
      (HTLV-I) isolated from an interleukin 2-dependent, CD8+ T-cell line derived from
      peripheral blood mononuclear cells of a healthy member of a remote, recently
      contacted hunter-horticulturalist group (Hagahai) in Madang province of Papua New
      Guinea. Antigenic characterization of this variant, designated PNG-1, by
      immunofluorescence, indicated no expression of gag-encoded proteins p19 and p24
      (even after incubation with 5-bromo-2'-deoxyuridine), using monoclonal and
      polyclonal antibodies against HTLV-I gag gene products. Virus-specific proteins
      of 15, 19, 46, 53, and 61/68 kDa were demonstrated by Western blot analysis,
      using sera from patients with serologically and/or virologically confirmed HTLV-I
      myeloneuropathy, sera from HTLV-I-infected rabbits, and antibodies prepared
      against the C terminus of the major envelope glycoprotein gp46. Restriction
      endonuclease maps of PNG-1 proviral DNA differed from that of a prototype strain
      of HTLV-I (MT-2), but, as verified by polymerase chain reaction, PNG-1 was
      definitely HTLV-I, not HTLV-II. Nucleotide sequencing and further molecular
      genetic studies of this variant may provide insights into the origin and
      evolution of HTLV-I.

PMID- 1996345
TI  - Sequence identity in the nick regions of IncP plasmid transfer origins and T-DNA
      borders of Agrobacterium Ti plasmids.
AB  - The IncP antibiotic-resistance plasmids transfer to a broad range of bacterial
      species. The RK2 origin of DNA transfer (oriT) consists of a 250-base-pair
      segment including the single-stranded cleavage site (nic) needed to generate the
      DNA strand believed to be transferred. Deletion derivatives and a bank of
      hydroxylamine-generated oriT mutants were screened for loss of transferability.
      DNA regions flanking both sides of nic are required for optimal transfer of the
      oriT clone. Of the chemically induced mutants, critical base-pair changes that
      dramatically reduced transfer frequency were found in a 10-base-pair region
      adjacent to nic. Relaxation (nicking) assays performed with these point mutants
      using protein-DNA complexes reconstituted in vitro revealed a correlation between
      DNA nicking and transfer frequency. Base-pair changes within the proximal arm of
      an inverted repeat upstream from the nick site resulted in reduced binding of the
      essential transfer protein TraJ and correspondingly reduced transfer frequencies.
      The results support a model of relaxosome formation involving at least two
      essential proteins: TraI and TraJ. The nick region defined by the point mutants
      was located in a segment known to be nearly identical in the related plasmid
      R751. This sequence was also found to be highly conserved in both border
      junctions of the transfer DNA (T-DNA) of plant tumor-inducing plasmids of
      Agrobacterium tumefaciens, indicating a relationship between IncP-mediated broad
      host-range bacterial conjugation and T-DNA transfer to plants.

PMID- 1996346
TI  - Localization and quantitation of tritiated compounds in tissue sections with a
      gaseous detector of beta particles: comparison with film autoradiography.
AB  - Quantitative analysis of tritium polymer standards and of brain sections labeled
      with tritiated vasopressin was carried out by using a gaseous detector of beta
      particles designed for this purpose. The gaseous detector showed major advantages
      compared with film autoradiography: the linearity and the large dynamic range of
      intensity measurements as well as the short time needed for data acquisition.

PMID- 1996347
TI  - The conserved GTPase center and variable region V9 from Saccharomyces cerevisiae
      26S rRNA can be replaced by their equivalents from other prokaryotes or
      eukaryotes without detectable loss of ribosomal function.
AB  - Using the "tagged" rRNA gene system, which allows in vivo mutational analysis of
      Saccharomyces cerevisiae rRNA, we studied the role of two distinct structural
      elements of 26S rRNA in ribosome biogenesis and function--namely, the
      evolutionarily highly conserved "GTPase center" located in domain II and the
      eukaroyote-specific variable region V9 in domain III. Replacement of the S.
      cerevisiae GTPase center with its counterpart from Escherichia coli did not
      affect the assembly of the mutant 26S rRNA into functional (as judged by their
      polysomal distribution) 60S subunits, indicating that the E. coli GTPase center
      functions efficiently in the context of the heterologous rRNA. Removal of most of
      the S. cerevisiae V9 region or replacement of this segment by the equivalent
      segment from mouse 28S rRNA also did not affect the formation of functional 60S
      subunits carrying the mutant 26S rRNA. Therefore, the V9 region does not seem to
      play a role in the biological functioning of the yeast 60S subunits, and these
      subunits appear to be able to accommodate V9 regions of various size and
      secondary structure without apparent loss of function.

PMID- 1996348
TI  - Independently arising macrophage mutants dissociate growth factor-regulated
      survival and proliferation.
AB  - Analysis of a simian virus 40-immortalized colony-stimulating factor 1 (CSF-1) 
      dependent macrophage cell line (BAC1.2F5) and independently arising autonomous
      mutants derived from it (aut4A, aut4A.1, aut2A, and aut2A.1) revealed distinct
      phenotypes. The parental line, BAC1.2F5, is dependent on CSF-1 for survival and
      growth. Of the mutants derived from BAC1.2F5, aut4A has lost the requirement of
      CSF-1 for survival; aut4A.1 (derived from aut4A) and aut2A grow in the absence of
      growth factor but proliferate more rapidly in its presence, and aut2A.1 (derived
      from aut2A) produces CSF-1 and proliferates as rapidly in the presence as in the
      absence of exogeneous CSF-1. The separation of the CSF-1 requirement for survival
      and proliferation observed in aut4A is also observed in a temperature-sensitive
      (ts) mutant tsgro1. At the nonpermissive temperature, tsgro1 cell proliferation
      is arrested, but the cells survive provided CSF-1 is present. The four cellular
      phenotypes observed--immortalization, loss of growth factor requirement for
      survival, loss of growth factor requirement for proliferation, and loss of growth
      factor-stimulated proliferation--indicate a divergence of the pathways of growth
      factor-regulated survival and proliferation and may represent phenotypes
      occurring at intermediate stages in tumor-cell progression.

PMID- 1996349
TI  - In vitro apolipoprotein B mRNA editing: identification of a 27S editing complex.
AB  - Specific apolipoprotein B (apoB) mRNA editing can be performed in vitro on apoB
      RNA substrates. Native gels and glycerol gradient sedimentation have been used to
      determine the physical properties of the in vitro editing activity in rat liver
      cytosolic S100 extracts. ApoB RNA substrates were progressively assembled as 27S
      complexes for 3 hr with similar kinetics as seen for the accumulation of edited
      RNA. Assembly was not observed on RNAs from apoB deletion constructs that did not
      support editing. The 27S complex contained both edited and unedited RNA
      sequences. Inhibition of 27S complex assembly by vanadyl-ribonucleoside complexes
      was accompanied by inhibition of editing. Based on these data, we propose that
      the 27S complex is the in vitro "editosome," A "mooring sequence" model for RNA
      recognition and editosome assembly has been proposed involving RNA sequences
      flanking the edited nucleotide.

PMID- 1996350
TI  - Search for cellular phosphorylation products of D-allose.
AB  - The all-cis hexose D-allose, fed to hamster fibroblast cultures over 14-20 hr,
      brings about a striking down-regulation of hexose transport. This down-regulation
      by allose is inhibited by 2,4-dinitrophenol. By using D-[14C]allose and thin
      layer chromatography, two types of products accumulated that have been identified
      as allose and allose phosphate. We suspect that allose phosphate might be the
      down-regulator.

PMID- 1996351
TI  - Epithelial-mesenchymal transformation of embryonic cardiac endothelial cells is
      inhibited by a modified antisense oligodeoxynucleotide to transforming growth
      factor beta 3.
AB  - During early cardiac development, the progenitor cells of the heart valves and
      membranous septa undergo an epithelial-mesenchymal transformation. Previous
      studies have shown that this transformation depends on the activity of a
      transforming growth factor beta (TGF beta) molecule produced by the heart. In the
      present study, we have used modified antisense oligodeoxynucleotides generated to
      nonconserved regions of TGF beta 1, -2, -3, and -4 to examine the possible roles
      of these members in this transformation. A phosphoramidate-modified
      oligonucleotide complementary to TGF beta 3 mRNA was capable of inhibiting normal
      epithelial-mesenchymal transformation by 80%. Unmodified oligonucleotides to TGF
      beta 3, modified oligonucleotides to TGF beta 1, -2, and -4, and two modified
      control oligonucleotides were unable to inhibit the transformation. These data
      demonstrate that a specific member of the TGF beta family, TGF beta 3, is
      essential for the epithelial-mesenchymal cell transformation.

PMID- 1996352
TI  - Mononuclear phagocytes: a major population of effector cells responsible for
      rejection of allografted tumor cells in mice.
AB  - To understand the in situ mechanism of immunological response of recipient
      animals to allografted tumor cells, the types of cells that infiltrated into the
      rejection site were examined. When Meth A cells (H-2d) were given i.p. to an
      allogeneic [C57BL/6 (H-2b)] strain of mouse, the tumor cells ceased to grow on
      the 6th day, accompanied by an i.p. infiltration of leukocytes. The tumor cells
      were totally eliminated from the peritoneal cavity around the 12th day. The
      highest cytotoxic activity against Meth A cells was obtained with the peritoneal
      exudate cells harvested on day 8. On this day, the exudate cells consisted of
      three populations when examined by flow cytometry, and each was isolated by
      sorting. Each of them appeared to be homogeneous, and they were morphologically
      identified as lymphocytes; granulocytes; and medium-sized, mononuclear, less
      granular cells. The cytotoxic activity was confined exclusively to the last
      population. The effector cells (H-2b) were cytotoxic against not only Meth A
      cells (H-2d) but also concanavalin A-stimulated allogeneic spleen cells [C3H/He
      (H-2k), CBA/N (H-2k), A/J (H-2a), BALB/c (H-2d), and DBA/2 (H-2d) strains of
      mouse]. The effector cells were totally inert against concanavalin A-activated
      syngeneic spleen cells [C57BL/6 (H-2b) and C57BL/10 (H-2b) strains of mouse]. The
      effector cells were phenotypically (Thy-1.2- CD3- Lyt-1- Lyt-2- L3T4-
      immunoglobulin- asialo GM1-), morphologically, and functionally distinct from
      cytotoxic T cells, natural killer cells, and lymphokine-activated killer cells
      but were adherent mononuclear phagocytes.

PMID- 1996353
TI  - Cloning and expression of human deoxycytidine kinase cDNA.
AB  - Deoxycytidine (dCyd) kinase is required for the phosphorylation of several
      deoxyribonucleosides and certain nucleoside analogs widely employed as antiviral
      and chemotherapeutic agents. Detailed analysis of this enzyme has been limited,
      however, by its low abundance and instability. Using oligonucleotides based on
      primary amino acid sequence derived from purified dCyd kinase, we have screened T
      lymphoblast cDNA libraries and identified a cDNA sequence that encodes a 30.5-kDa
      protein corresponding to the subunit molecular mass of the purified protein.
      Expression of the cDNA in Escherichia coli results in a 40-fold increase in dCyd
      kinase activity over control levels. In dCyd kinase-deficient murine L cells,
      transfection with dCyd kinase cDNA in a mammalian expression vector produces a
      400-fold increase over control in dCyd phosphorylating activity. The expressed
      enzyme has an apparent Km of 1.0 microM for dCyd and is also capable of
      phosphorylating dAdo and dGuo. Northern blot analysis reveals a single 2.8
      kilobase mRNA expressed in T lymphoblasts at 5- to 10-fold higher levels than in
      B lymphoblasts, and decreased dCyd kinase mRNA levels are present in T
      lymphoblast cell lines resistant to arabinofuranosylcytosine and dideoxycytidine.
      These findings document that this cDNA encodes the T-lymphoblast dCyd kinase
      responsible for the phosphorylation of dAdo and dGuo as well as dCyd and
      arabinofuranosylcytosine.

PMID- 1996354
TI  - Very long charge runs in systemic lupus erythematosus-associated autoantigens.
AB  - Systemic lupus erythematosus and other chronic systemic autoimmune diseases are
      associated with circulating autoantibodies reactive with a limited set of mostly
      nuclear proteins. Using rigorous statistical methods we have identified segments
      of highly significant charge concentration in the majority of the characteristic
      nuclear and cytoplasmic autoantigens. Extremely long runs of charged residues,
      including some sequences of greater than 20 consecutive charged residues (purely
      acidic or mixed basic and acidic), occur in about a third of these proteins,
      whereas equivalent runs are found in less than 3% of other mammalian proteins.
      The other sequences have less extreme charge clusters, the type and location of
      which are often conserved between several otherwise nonsimilar antigens. We
      propose that supercharged surfaces render the targeted host proteins strongly
      immunogenic and that antinuclear antibody profiles might result from chronic
      exposure to intracellular contents, possibly in conjunction with crossreactive
      viral products. The limited number of potential systemic autoantigens may partly
      be due to the rarity of requisite charge properties.

PMID- 1996355
TI  - Microglial progenitors with a high proliferative potential in the embryonic and
      adult mouse brain.
AB  - Single cell suspensions, prepared from brain stem, cerebellum, and forebrain
      parenchyma of embryonic and adult mice, were plated on monolayers of an
      astroglial cell line derived from a spontaneously immortalized mouse cerebellar
      culture, the D19 clone. A few of the brain cells adhering to the D19 monolayers
      were immunoreactive to the Mac-1 antibody, which labels all cells of the
      monocytic and granulocytic lineages. The Mac-1-positive cells proliferated
      vigorously and later most of them acquired the F4/80 epitope specific for
      macrophages and microglia cells. Studies in clonal conditions allowed development
      of large colonies of about 2 x 10(5) cells that expressed typical microglia
      markers. Bone marrow Mac-1-positive cells cocultured on D19 monolayers were also
      induced to proliferate, whereas peritoneal macrophages were not. D19 astrocytes
      express macrophage colony-stimulating factor (CSF-1) activity at a high level,
      and their conditioned media induced the proliferation of brain and bone marrow
      Mac-1-positive cells. A specific anti-CSF-1 antiserum completely blocked bone
      marrow macrophage progenitor proliferation and significantly reduced the
      multiplication of microglial precursors induced by the D19-conditioned medium.
      These data indicate that the embryonic and adult mouse brain parenchyma contains
      potential progenitors for microglial cells.

PMID- 1996356
TI  - A spectroscopic and calorimetric study of the melting behaviors of a "bent" and a
      "normal" DNA duplex: [d(GA4T4C)]2 versus [d(GT4A4C)]2.
AB  - We have calorimetrically detected and energetically characterized a premelting
      event in the "bent" duplex [d(GA4T4C)]2 that is absent in the "normal" duplex
      [d(GT4A4C)]2. This premelting may correspond to the thermally induced "unbending"
      of the duplex. Specifically, we have used a combination of spectroscopic and
      calorimetric techniques to evaluate whether differences in the electrophoretic
      and hydrogen exchange properties of the bent duplex, [d(GA4T4C)]2, and the normal
      duplex, [d(GT4A4C)]2, are paralleled by differences in the equilibrium melting
      properties of these duplexes. Our results reveal that the bimolecular global
      meltings of both duplexes exhibit two-state behavior and are characterized by the
      expected thermodynamic changes, as well as the expected salt-dependencies.
      Significantly, however, at temperatures below duplex melting and over a similar
      temperature range in which the aberrant electrophoretic mobility is observed
      (approximately less than 35 degrees C), the bent duplex exhibits calorimetric
      premelting behavior absent in the normal duplex. Analysis of the calorimetric
      data in this preglobal melting domain (approximately less than 35 degrees C)
      allows us to estimate a lower-limit value of 1.6 kcal/(mol-base pair) for the
      thermally induced unbending of the decameric duplex.

PMID- 1996357
TI  - Binding protein BiP is required for translocation of secretory proteins into the
      endoplasmic reticulum in Saccharomyces cerevisiae.
AB  - The endoplasmic reticulum of mammalian cells contains a heat shock protein of
      approximately 70 kDa (hsp70) termed binding protein BiP that is thought to
      promote the folding and subunit assembly of newly synthesized proteins. To study
      BiP function, we placed the BiP-encoding gene from Saccharomyces cerevisiae under
      the control of a regulated promoter and examined the effects of BiP depletion.
      Reduction of BiP protein to about 15% of normal levels led to a profound
      reduction in secretion of alpha factor and invertase. At the same time,
      unglycosylated precursors of these proteins accumulated intracellularly. The
      predominant form of the invertase precursor had undergone signal sequence
      cleavage but accumulated as a soluble species in the cytosol. In contrast, the
      alpha-factor precursor was exclusively in the signal-uncleaved form. It
      sedimented with microsomal membranes and was exposed at the cytoplasmic face in a
      protease-resistant form. These findings suggest that, in yeast, BiP function is
      required for translocation of soluble proteins into the endoplasmic reticulum at
      a stage beyond the initial nascent chain-membrane association.

PMID- 1996358
TI  - Resolution of the African hominoid trichotomy by use of a mitochondrial gene
      sequence.
AB  - Mitochondrial DNA sequences encoding the cytochrome oxidase subunit II gene have
      been determined for five primate species, siamang (Hylobates syndactylus),
      lowland gorilla (Gorilla gorilla), pygmy chimpanzee (Pan paniscus), crab-eating
      macaque (Macaca fascicularis), and green monkey (Cercopithecus aethiops), and
      compared with published sequences of other primate and nonprimate species.
      Comparisons of cytochrome oxidase subunit II gene sequences provide clear-cut
      evidence from the mitochondrial genome for the separation of the African ape
      trichotomy into two evolutionary lineages, one leading to gorillas and the other
      to humans and chimpanzees. Several different tree-building methods support this
      same phylogenetic tree topology. The comparisons also yield trees in which a
      substantial length separates the divergence point of gorillas from that of humans
      and chimpanzees, suggesting that the lineage most immediately ancestral to humans
      and chimpanzees may have been in existence for a relatively long time.

PMID- 1996359
TI  - AIDS epidemiology: inconsistencies with human immunodeficiency virus and with
      infectious disease.
AB  - The newly defined syndrome AIDS includes 25 unrelated parasitic, neoplastic, and
      noninfectious indicator diseases. Based on epidemiological correlations, the
      syndrome is thought to be due to a new, sexually or parenterally transmitted
      retrovirus termed human immunodeficiency virus (HIV). The following
      epidemiological data conflict with this hypothesis. (i) Noncorrelations exist
      between HIV and AIDS; for example, the AIDS risks of infected subjects vary
      greater than 10-fold with their gender or country. Abnormal health risks that are
      never controlled as independent AIDS causes by AIDS statistics, such as drug
      addiction and hemophilia, correlate directly with an abnormal incidence of AIDS
      diseases. Above all, the AIDS diseases occur in all risk groups in the absence of
      HIV. (ii) American AIDS is incompatible with infectious disease, because it is
      almost exclusively restricted to males (91%), because if it occurs, then only on
      average 10 years after transfusion of HIV, because specific AIDS diseases are not
      transmissible among different risk groups, and because unlike a new infectious
      disease, AIDS has not spread exponentially since the AIDS test was established
      and AIDS received its current definition in 1987. (iii) Epidemiological evidence
      indicates that HIV is a long-established, perinatally transmitted retrovirus. HIV
      acts as a marker for American AIDS risks, because it is rare and not
      transmissible by horizontal contacts other than frequent transfusions,
      intravenous drugs, and repeated or promiscuous sex. It is concluded that American
      AIDS is not infectious, and suggested that unidentified, mostly noninfectious
      pathogens cause AIDS.

PMID- 1996360
TI  - Photosensitized destruction of human bladder carcinoma cells treated with chlorin
      e6-conjugated microspheres.
AB  - A photosensitizer conjugate, chlorin e6 (Ce6) covalently bound to 1-micron
      diameter polystyrene microspheres, has been investigated in the photodynamic
      destruction of MGH-U1 human bladder carcinoma cells in vitro. The microspheres
      were taken up avidly by the carcinoma cells; confocal laser scanning fluorescence
      microscopy showed them to be localized in the cytoplasm, apparently within
      lysosomes, visualized by labeling with acridine orange. In contrast, fluorescence
      of unconjugated Ce6 was present within most cellular membranes. Use of Ce6
      microsphere conjugates led to a 20-fold-higher mean intracellular concentration,
      compared with unconjugated Ce6. Cells incubated in the presence of Ce6
      microsphere conjugates (0.43 microM equivalent) and subsequently irradiated at
      659 nm with a dye laser pumped by an argon-ion laser showed dose-dependent
      phototoxicity, leading to total inhibition of colony formation at a radiant
      exposure of 5J/cm2; in contrast, cells incubated with either unconjugated Ce6
      (0.43 microM) or unconjugated microspheres before laser irradiation were
      unaffected. Cells pretreated with Ce6-microsphere conjugates and irradiated in
      the presence of 90% 2H2O showed significantly increased phototoxicity, an effect
      consistent with an important role for excited-state singlet oxygen in the
      mechanism of injury. In solution, however, photosensitized generation of singlet
      oxygen with Ce6-microsphere conjugates was 9 times less efficient than with
      unconjugated Ce6. The markedly greater phototoxicity of Ce6-microsphere
      conjugates compared to unconjugated Ce6 was therefore a consequence of the high
      intracellular Ce6 concentration attained by phagocytosis of the conjugates and
      their particular sites of intracellular localization. Thus, these conjugates are
      an efficient system for the delivery of photosensitizing drugs to carcinoma
      cells.

PMID- 1996362
TI  - Who should be doing the research in nursing?

PMID- 1996361
TI  - Leukemia initiated by hemopoietic stem cells expressing the v-abl oncogene.
AB  - We report a mouse model with which to study leukemogenesis initiated by a
      specific genetic change introduced into a primary lymphoid-myeloid pluripotent
      stem cell. Fetal liver hemopoietic cells were infected with a high titer of
      helper-free Abelson murine leukemia virus (A-MuLV) and were used to reconstitute
      lethally irradiated mice. Two weeks later, progenies of a single primitive
      hemopoietic stem cell carrying a specifically integrated A-MuLV proviral DNA
      could be detected in both colony-forming units in spleen and myeloid colony
      forming cells in the bone marrow. Beginning at 3 weeks after transplantation, the
      recipients developed elevated leukocyte counts, splenomegaly, and increase of
      blast cells in the peripheral blood. Multiple clones of A-MuLV-infected cells
      were infused into each recipient. However, in the same animal, DNA extracted from
      various affected organs and from factor-independent lymphoid and myeloid
      immortalized cells all contained an identical, specifically integrated proviral
      genome. The A-MuLV-infected stem cells differentiated into various lineages of
      hemopoietic cells. Our data show that the expression of the v-abl oncogene in a
      primary lymphoid-myeloid hemopoietic stem cell directly initiates leukemogenesis
      by stimulating factor-independent growth. The monoclonal-type disease development
      seen in these animals may require the occurrence of an additional genetic event.

PMID- 1996364
TI  - Planning for the best start in life. A guide to infant feeding.
AB  - Feeding in infancy is vitally important to future development. Rapid growth and
      development mean infants need considerable nutritional support, which makes them
      vulnerable if they are not fed adequately.

PMID- 1996363
TI  - Accidental hypothermia.

PMID- 1996365
TI  - Wound care: can the nursing process help? Implementing a wound care policy.
AB  - Nurses working in wound care must do more than rely on favoured wound care
      dressings. The nursing process can help them implement a structured care plan
      around the needs of individual patients, and facilitate patient understanding.

PMID- 1996366
TI  - In service to meet your research needs. The Index of Nursing Research Information
      Service.

PMID- 1996367
TI  - Understanding salpingitis. A pelvic inflammatory infection.
AB  - Salpingitis is an infection of the fallopian tubes which requires prompt
      diagnosis and treatment. Nurses need to be fully informed about the condition, so
      they can reassure women under treatment and see their needs are met.

PMID- 1996368
TI  - An opportunity we must not miss. Computers and nursing practice.
AB  - Computers can offer nurses considerable benefits, cutting much of the time spent
      on administrative and clerical duties. Nurses need to forget their apprehensions
      and take advantage of the wealth of opportunities they provide, while
      acknowledging they can never replace hands-on nursing care.

PMID- 1996369
TI  - A choice to help meet women's needs. Developments in female urethral catheters.
AB  - Catheterisation can be a source of embarrassment and discomfort for women, while
      nurses are often unaware of the choice of catheters available. By keeping
      themselves fully informed, nurses can ensure patients are provided with a choice
      of catheter which meets their needs.

PMID- 1996370
TI  - Interaction of lymphocytes and high endothelial venules in irradiated lymph
      nodes.
AB  - After total-body exposure to various doses of ionizing radiation, the ability of
      lymphocytes to interact specifically with high endothelial venules of rat
      cervical and mesenteric lymph nodes was analyzed in frozen sections. Following a
      radiation dose of 1.5 Gy, high endothelial venules remained intact and the
      binding of unirradiated lymphocytes to the venules was enhanced relative to
      unirradiated controls. At radiation doses above 5.0 Gy, damage to high
      endothelial venules was observed histologically as well as assessed functionally.
      There was a significant decrease in specific lymphocyte-venule binding and a
      significant increase in nonspecific binding. These findings suggest that
      radiation-induced damage to high endothelial venules might play a role in
      radiation-induced immunosuppression by interfering with the normal passage of
      lymphocytes from the blood into lymph nodes via a specific interaction between
      lymphocytes and high endothelial venules.

PMID- 1996371
TI  - Use of unstable chromosome aberrations for biological dosimetry after the first
      postirradiation mitosis.
AB  - The loss of unstable chromosome aberrations after the first postirradiation
      mitosis makes their use difficult in radiation dosimetry. We describe here a
      method which, in a cell population observed at this stage, allows retrospective
      estimation of the frequencies of the unstable aberrations induced at the time of
      irradiation, and their use as a dosimeter. The laws controlling the behavior of
      unstable aberrations during mitosis were defined from a large-scale experiment on
      irradiated human lymphocytes. For cells undergoing the first, second, or third
      mitosis after irradiation, relationships were determined between the frequency,
      at irradiation time, of acentric fragments not arising from formation of
      dicentrics or rings, and the ratio of dicentrics and centric rings appearing
      without acentric fragments to the total number of dicentrics plus rings. On the
      basis of this ratio, the method described here provides an assessment of the
      postirradiation mitotic activity in a cell population. This assessment permitted
      estimation of the cell distribution and frequency of dicentrics plus centric
      rings, and of the frequency of acentric fragments at the time of irradiation. The
      use of this method for retrospective dosimetry after whole-body irradiation under
      various conditions of exposure is illustrated.

PMID- 1996372
TI  - Association of WR-1065 with CHO AA8 cells, nuclei, and nucleoids.
AB  - The radioprotector WR-1065 (N-(2-mercaptoethyl)-1,3-diaminopropane) has been
      shown to be the active moiety involved in protecting mammalian cells from the
      cytotoxic and mutagenic effects of ionizing radiation after administration of WR
      1065 or the phosphorylated form, WR-2721. Initial experiments demonstrated that,
      in our hands, WR-1065 protects Chinese hamster AA8 cells from killing by (a)
      mechanism(s) other than induction of hypoxia. AA8 cells were then incubated in
      the presence of [14C]WR-1065 to determine whether association of WR-1065 in vivo
      was random or targeted to the nucleus or the nuclear matrix. The kinetics of
      incorporation of labeled material showed rapid incorporation for the first 30 min
      and little, if any, additional incorporation over the next 2.5 h. Examination of
      nuclei and nucleoids generated from the AA8 cells indicated that approximately
      10% of the drug was localized in the nucleus and the drug that remained was not
      dislodged with repeated washes of the filters. Association kinetics of the drug
      with nuclei and nucleoids indicated that there was little increase in drug
      association with time, suggesting that there may be a limited number of strong
      association sites in the nucleus, but these sites are either with DNA or with
      matrix proteins. Exposure of the AA8 cells to 6 Gy of 60Co gamma rays did not
      significantly alter the association of the drug with AA8 cells. Incubating AA8
      cells in [14C]WR-1065 for 30 min and then incubating in drug-free medium
      indicated that nearly all of the drug was lost from cells within the first 5 min
      of incubation in drug-free medium. The low level of tightly bound matrix
      associated label may be important in generating alterations in matrix
      organization that have been observed previously in this laboratory.

PMID- 1996373
TI  - Reductions in calcium uptake induced in rat brain synaptosomes by ionizing
      radiation.
AB  - Gamma irradiation (60Co) reduced KCl-stimulated voltage-dependent 45Ca2+ uptake
      in whole-brain, cortical, and striatal synaptosomes. The time course (3, 10, 30,
      and 60 s) of calcium uptake by irradiated (3 Gy) and nonirradiated synaptosomes,
      as well as the effect of KCl (15-65 mM), was measured in whole-brain
      synaptosomes. The fastest and highest rate of depolarization-dependent calcium
      uptake occurred at 3 s with 65 mM KCl. Irradiation reduced calcium uptake at all
      incubation times and KCl concentrations. Bay K 8644 enhancement of KCl-stimulated
      calcium influx was also reduced by radiation exposure. Nimodipine binding to
      dihydropyridine (DHP) L-type calcium channel receptors was not altered following
      radiation exposure. These results demonstrate an inhibitory effect of ionizing
      radiation on the voltage-sensitive calcium channels in rat brain synaptosomes
      that are not mediated by DHP receptors.

PMID- 1996374
TI  - Repopulation in murine skin after X-ray treatments with multiple fractions per
      day.
AB  - The kinetics of repopulation of clonogens in skin after fractionated X-ray
      exposures was studied in a series of experiments using a top-up design. The feet
      of mice were exposed to small X-ray doses (1.5 or 2 Gy), given two or three times
      a day on consecutive days with a minimum interfraction interval of 8 h. A single
      top-up dose of d(4)-Be neutrons was then given at various intervals after the
      last X-ray fraction, typically on Days 1,4,8, 15, and 19. The acute skin reaction
      produced was scored an analyzed by both a standard 23-day averaging and a 7-day
      averaging procedure. Either method gave similar results and led to the same
      conclusions. The amount of top-up dose needed to produce a fixed skin reaction
      was used as a measure of the net effect of the X-ray treatments. This net effect
      is a result of the initial reduction in skin clonogens due to X rays, and their
      repopulation before the top-up dose was given. Repopulation was not detected
      during any of these courses of fractionated treatment, up to an overall time of
      at least 12 and possibly 16 days. On completion of X-ray schedules lasting 6-16
      days, repopulation started 4 days later. In contrast, this delay lengthened to
      approximately 8 days for shorter overall treatment times of 3-4 days. Once
      repopulation started, it proceeded rapidly over 11 days so that by 15 days after
      the cessation of X rays, the skin was restored almost to its normal state with
      respect to radiosensitivity. The residual damage from Day 15 to Day 19
      postirradiation was 3-13% of a full-effect level. The rate of repopulation can be
      expressed as a clonogen doubling time (Tclon), assuming that an average skin
      reaction of 1.5 is equivalent to a clonogen surviving fraction of 1.7 x 10(-5).
      Tclon varied inversely with the amount of initial damage inflicted by the X rays,
      with the shortest values (1-1.3 days) seen following X-ray doses that gave an
      initial damage level of 60-80% of full effect. These data are consistent with a
      hypothesis that damage is "sensed" only 10-12 days after the first X-ray
      fraction, which provides the stimulus for repopulation of the target cells in the
      basal layer, the keratinoblasts.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1996375
TI  - The sensitivity of the thoracolumbar spinal cord of the mouse to hyperthermia.
AB  - Twelve millimeters of the thoracolumbar spinal cord of mice has been treated with
      a radiofrequency heating system which has been shown previously to produce
      localized and controllable elevation of temperature. The severity of neurological
      damage was assessed by measuring the reduction in the reflex leg extension of the
      hind legs of the mice from video-recorded images and by scoring the performance
      of the mice by a negative geotaxis test. The response to treatment was rapid with
      maximum paralysis occurring within a few days after treatment. Only minor
      symptoms were observed in those animals which had not developed paralysis within
      2 weeks. A 40% reduction in the reflex leg extension was chosen as an end point,
      and the percentage of mice having reached the end point for different thermal
      doses was determined in groups of nine mice. The ED50 for heating for 1 h was
      43.1 degrees C and for heating at 45 degrees C was 10.8 min. An increase in
      temperature by 1 degree C required a decrease in time by a factor of 2.25 to
      produce the same effect. Thermotolerance was observed 24 h after preheating at 45
      degrees C for 1.9 min with a thermotolerance ratio of 1.7. The rapid response and
      high sensitivity of the spinal cord will have to be taken into consideration in
      the clinical application of hyperthermia.

PMID- 1996377
TI  - Stage-specific damage to synaptonemal complexes and metaphase chromosomes induced
      by X rays in male mouse germ cells.
AB  - Synaptonemal complexes reveal mutagen-induced effects in germ cell meiotic
      chromosomes. This study was aimed at characterizing relationships between damage
      to synaptonemal complexes and metaphase I chromosomes following radiation
      exposure at various stages of spermatogenesis. Male mice were irradiated with
      doses of 0, 2, or 4 Gy, and spermatocytes were harvested at times consistent with
      earlier exposures as spermatogonial stem cells, preleptotene cells (premeiotic
      DNA synthesis), or meiotic prophase cells. After stem-cell exposure, twice as
      many rearrangements were observed in synaptonemal complexes as in metaphase I
      chromosomes. Irradiation during premeiotic DNA synthesis resulted in dose-related
      increases in synaptonemal complex breakage and rearrangements (including novel
      forms) and in metaphase chromosomal aberrations. Following prophase exposure,
      various types and levels of damage to synaptonemal complexes and metaphase
      chromosomes were observed. Irradiation of zygotene cells led to high frequencies
      of chromosome multivalents in metaphase I without a correspondingly high level of
      damage in preceding prophase synaptonemal complexes. Thus irradiation of
      premeiotic and meiotic cells results in variable relationships between damage to
      synaptonemal complexes and metaphase chromosomes. Interpretations of these
      relationships are based upon what is known about both radiation clastogenesis and
      the structural/temporal relationships between synaptonemal complexes at prophase
      and chromosomes at metaphase I of meiosis.

PMID- 1996376
TI  - Effect of fibroblast implants on wound healing of irradiated skin: assay of wound
      strength and quantitative immunohistology of collagen.
AB  - The role of dermal fibroblasts in the expression of radiation-induced damage to
      the skin was studied. Fibroblasts from neonatal mice were cultured, harvested,
      and injected into full-depth surgical incisions in the dorsal area of mouse skin,
      which had been previously locally irradiated by 18 Gy X rays. As a control, cells
      irradiated with a dose of 20 Gy were also injected. The effect of radiation and
      fibroblast implants on the gain of skin wound strength was assayed. In an
      additional experiment freshly isolated cells were implanted. Two weeks following
      wounding the irradiated skin had reached only about a third of the strength of
      unirradiated skin. A significant increase of wound strength in irradiated skin
      was observed when 1.5-2 x 10(6) cultured fibroblasts or freshly isolated
      fibroblasts were injected into the 20-mm-long wound bed. Irradiated cells had
      significantly less effect. This suggests that implanting isolated syngeneic cells
      may "rescue" wounds from the effect of prior irradiation. Semiquantitative
      immunohistology of types I and III collagen was performed in parallel using a
      video image digitizing system. Levels of both types I and III collagen were
      altered in the dermis and the wound tissues in irradiated skin, but the implant
      of cultured fibroblasts did not affect notably the total levels and the
      disposition of the two collagen isotypes.

PMID- 1996378
TI  - Investigation of the neutral filter elution technique I. Effects of pore density
      and pore diameter on elution rate at pH 9.6.
AB  - To understand better the biophysical mechanism of neutral filter elution (pH
      9.6), we eluted genomes of known size and shape: coliphage T4c (Mr 1.15 x 10(8),
      E. coli (Mr 2.7 x 10(9)), and Chinese hamster lung fibroblasts (V79, Mr 2-4 x
      10(10)). DNA eluted through 15% sucrose atop the filter in a biphasic pattern.
      The elution rate of the initial component correlated (r greater than 0.97)
      exponentially with 1/Mr for monodisperse samples of DNA eluted through pore sizes
      0.1-3.0 microns. Using this relationship between elution rate and Mr, we
      estimated Mn of polydisperse, X-irradiated (253 Gy) samples of DNA from E. coli
      or V79 cells to be 3.15 +/- 1.46 and 1.42 +/- 0.33, respectively, compared to
      expected values of 2.93 and 3.52 (10(8) Da). The best predictor of elution rate
      for DNA from T4c and intact and X-irradiated V79 cells was pore density, and pore
      diameter for DNA from X-irradiated E. coli. The rate of elution of DNA from
      unirradiated E. coli was unrelated to pore density or diameter. While the
      mechanism of neutral filter elution remains unknown, its use for linear DNAs with
      Mn ca. 10(8) Da appears to be valid quantitatively.

PMID- 1996379
TI  - The observed relationship between the occurrence of acute radiation effects and
      leukemia mortality among A-bomb survivors.
AB  - In an analysis of a follow-up study of a fixed population of 73,330 atomic bomb
      survivors in Hiroshima and Nagasaki, the slope of an estimated dose response
      between ionizing radiation and leukemia mortality was found to be steeper (P less
      than 0.002), by a factor of 2.4, among those who reported epilation within 60
      days of the bombings, compared to those who did not experience this sign of acute
      radiation exposure. The strength of this empirical finding as evidence of
      biological association in individual radiosensitivity for these two end points is
      studied here. The major factor complicating the interpretation of this finding as
      evidence of such an association is the degree of imprecision of the radiation
      dosimetry system used in assignment of radiation doses to the A-bomb survivors.
      Using models recently suggested for dealing with dosimetry errors in
      epidemiological analysis of the A-bomb survivor data, the sensitivity of the
      apparent association between leukemia mortality and severe epilation to the
      assumed level of dosimetry error is investigated.

PMID- 1996380
TI  - Frequent chest X-ray fluoroscopy and breast cancer incidence among tuberculosis
      patients in Massachusetts.
AB  - The incidence of breast cancer was determined in 4940 women treated for
      tuberculosis between 1925 and 1954 in Massachusetts. Among 2573 women examined by
      X-ray fluoroscopy an average of 88 times during lung collapse therapy and
      followed for an average of 30 years, 147 breast cancers occurred in contrast to
      113.6 expected [observed/expected (O/E) = 1.29; 95% confidence interval (CI) =
      1.1-1.5]. No excess of breast cancer was seen among 2367 women treated by other
      means: 87 observed versus 100.9 expected. Increased rates for breast cancer were
      not apparent until about 10 to 15 years after the initial fluoroscopy
      examination. Excess risk then remained high throughout all intervals of follow
      up, up to 50 years after first exposure. Age at exposure strongly influenced the
      risk of radiation-induced breast cancer with young women being at highest risk
      and those over age 40 being at lowest risk [relative risk (RR) = 1.06]. Mean
      radiation dose to the breast was estimated to be 79 cGy, and there was strong
      evidence for a linear relationship between dose and breast cancer risk. Allowing
      for a 10-year minimum latent period, the relative risk at 1 Gy was estimated as
      1.61 and the absolute excess as 10.7 per 10(4) woman-years per gray. When
      compared to other studies, our data suggest that the breast is one of the most
      sensitive tissues to the carcinogenic force of radiation, that fractionated
      exposures are similar to single exposures of the same total dose in their ability
      to induce breast cancer, that risk remains high for many years after exposure,
      and that young women are especially vulnerable to radiation injury.

PMID- 1996381
TI  - Thermal sensitivity and radiosensitization in Chinese hamster V79 cells exposed
      to 2-aminopurine or 6-thioguanine.
AB  - Chinese hamster V79 cells were exposed to 10(-6) mol liter-1 2-aminopurine (2-AP)
      or 6-thioguanine (6-TG) for 18 or 40 h, and then tested for sensitivity to X
      rays, heat, or a combined treatment of heat and radiation. Cells exposed to 6-TG
      were sensitive to X rays, while those treated with 2-AP showed little or no
      sensitivity. At 42 degrees and 45 degrees C moderate sensitization resulted from
      2-AP treatment, with greater sensitization resulting from treatment with 6-TG.
      Combined heat and X-ray treatment of cells exposed to 2-AP yielded sensitization
      similar to heat treatment alone, while cells exposed to 6-TG before receiving the
      combined treatment showed a degree of sensitization greater than that due to
      either treatment by itself but less than that of the two treatments added
      together. Uptake of the purine analogues into cellular DNA was measured by high
      pressure liquid chromatography. At the 1% detection level, after either an 18- or
      a 40-h exposure of cells to 10(-6) mol liter-1 2-AP or 6-TG, no base substitution
      was found. Analysis of cell cycle distributions by flow cytometry revealed only
      very small changes following exposure of cells to the purine analogues.

PMID- 1996383
TI  - Mechanism of the inhibition of cell division of plant cells by ionizing
      radiations.

PMID- 1996382
TI  - Saturation of DNA repair measured by alkaline elution.
AB  - To determine whether the half-times (T1/2) of the DNA repair processes measured
      by alkaline elution increased in a dose-dependent manner, exponentially growing
      9L/Ro rat brain tumor cells were irradiated with doses of 15-50 Gy, and their DNA
      repair kinetics was measured by alkaline elution. At 15 Gy, the DNA repair
      kinetics was biphasic with the fast phase having a T1/2 approximately 6 min and
      the slow phase having a T1/2 approximately 42 min. As the dose was increased to
      50 Gy, the fast-phase T1/2 remained at approximately 6 min, but the slow-phase
      T1/2 increased to approximately 87 min. Although a dose-dependent increase in the
      T1/2 of the slow phase of DNA repair (saturation) was measured by alkaline
      elution, both the absolute value of the slow-phase T1/2 and the dependency of the
      slow-phase T1/2 on dose were less than those measured by alkaline sucrose
      gradient sedimentation in zonal rotors with slow reorienting gradient capability.
      Thus these two techniques appear either to depend on different hydrodynamic
      properties of the DNA or to have different coefficients of dependency for the
      same hydrodynamic properties of the DNA. The lower sensitivity for detection of
      the dose dependency of DNA repair makes it unlikely that the alkaline elution
      technique will be useful for quantitatively relating the shape of mammalian cell
      survival curves to the doses at which saturation of a DNA repair process occurs.

PMID- 1996384
TI  - Doppler US: the basics.
AB  - Doppler ultrasonography (US) is an invaluable tool in the diagnosis of occlusive
      vascular disease and is assuming increasing importance in the diagnosis of
      abdominal, pelvic, and fetal disorders. The author presents for new users the
      basic physics principles of Doppler US in his discussions of the Doppler
      principle, instrumentation, signal processing and display, artifacts, and
      interpretation of data. An understanding of these principles will assist
      radiologists in using the full potential of Doppler US in the diagnostic workup.

PMID- 1996385
TI  - Brief history of gastrointestinal radiology.

PMID- 1996386
TI  - Image interpretation session. Bronchial carcinoid tumor of the left lower lobe
      with postobstructive bronchiectasis.

PMID- 1996387
TI  - Image interpretation session. Viral optic neuritis.

PMID- 1996388
TI  - Image interpretation session. Pedunculated, localized fibrous mesothelioma
      arising from the left parietal pleura.

PMID- 1996389
TI  - Image interpretation session. Intrasellar chondroma.

PMID- 1996390
TI  - Image interpretation session. Intraosseous gout.

PMID- 1996391
TI  - Image interpretation session. Castleman disease (giant lymph node hyperplasia).

PMID- 1996392
TI  - Image interpretation session. Solid and papillary epithelial neoplasm of the
      pancreas.

PMID- 1996393
TI  - Pediatric case of the day. Esophageal foreign body with perforation and
      mediastinitis.

PMID- 1996394
TI  - Ultrasound case of the day. Epidermoid cyst of the testicle.

PMID- 1996395
TI  - General case of the day. Hemangioma of the bladder.

PMID- 1996396
TI  - Imaging self referral: Willie Sutton strikes again.

PMID- 1996397
TI  - Seat belt injuries: radiologic findings and clinical correlation.
AB  - The seat belt syndrome consists of skeletal, soft-tissue, and visceral injuries
      associated with use of two- and three-point restraints in patients involved in
      motor vehicle accidents. Skin abrasions of the neck, chest, and abdomen--the
      classic seat belt sign--indicate internal injury in 30% of cases. Neck abrasions
      are associated with injuries to the carotid artery, larynx, and cervical spine;
      chest abrasions, with fractures of the sternum, ribs, and clavicles and injuries
      to the heart and thoracic aorta; and abdominal abrasions, with mesenteric tears,
      bowel perforation and hematoma, Chance fractures, and injuries to the abdominal
      aorta. The seat belt sign should prompt a diligent search for related injuries.

PMID- 1996398
TI  - Simplified approach to umbilical remnant abnormalities.
AB  - To facilitate an understanding of abnormalities related to the umbilical
      remnants, the authors present a simplified classification scheme on the basis of
      embryologic anatomic relationships. In a type 1 remnant, the entire duct
      (vitelline or urachus) is patent; in type 2, only one end is patent; and in type
      3, only the midportion is patent. The authors illustrate and describe various
      entities in terms of this classification, including patent vitelline duct,
      umbilical sinus, Meckel diverticulum, vitelline cyst, patent urachus, urachal
      sinus, urachal diverticulum, and urachal cyst. With this scheme, imaging
      characteristics of the types of remnant abnormalities can be predicted. The
      result is a cogent approach to the radiologic evaluation of the patient with a
      suspected umbilical remnant anomaly.

PMID- 1996399
TI  - Fat-containing soft-tissue masses of the extremities.
AB  - The authors review the radiologic spectrum of fat-containing soft-tissue masses
      of the extremities, with emphasis on computed tomography, magnetic resonance
      imaging, and pathologic correlation. These masses include both common and
      uncommon, benign and malignant lesions, such as lipoma, intramuscular and
      intermuscular lipoma, neural fibrolipoma, lipoblastoma, lipomatosis, hibernoma,
      hemangioma, elastofibroma, and liposarcoma, as well as lesions that may mimic fat
      containing soft-tissue masses. Imaging studies of fat-containing lesions will
      often allow a specific presumptive diagnosis. When a specific diagnosis is not
      possible, however, knowledge of the spectrum of fat-containing lesions will allow
      a suitably ordered differential diagnosis.

PMID- 1996400
TI  - MR imaging in the differential diagnosis of scrotal and testicular disease.
AB  - It is frequently impossible to discriminate between various causes of scrotal
      pain and swelling by means of clinical examination and ultrasound (US) alone.
      Surgical exploration is necessary in cases of indefinite differential diagnosis.
      For evaluation of the diagnostic potential of magnetic resonance (MR) imaging in
      scrotal disease, 200 patients with testicular abnormalities were studied. For 74
      of these patients, the diagnosis was cancer, based on clinical and US findings.
      MR imaging demonstrated malignant disease in 54 patients and benign disease in
      20. All of the MR imaging findings were confirmed at surgical biopsy. Despite
      high costs of the procedure, the authors believe that MR imaging is a useful aid
      for diagnosis in cases of indefinite findings in scrotal and testicular disease.

PMID- 1996401
TI  - Mitogenesis and the search for new targets for anticancer drug design.
AB  - An exciting new approach to the treatment of cancer is the development of
      therapeutic strategies which target growth factors and the signal transduction
      pathways elicited by them. The rationale for targeting the processes which
      regulate cell proliferation rests on the contention that the malignant phenotype
      is maintained as a result of alterations in the biochemistry of growth control.
      The challenge is to design novel anticancer agents which exploit qualitative or
      quantitative differences in the biochemical elements controlling tumour cell
      growth and thereby achieve tumour selectivity. A wide variety of drugs are
      currently under development and include agents which block growth factor-receptor
      interaction, or which inhibit the action or formation of second messengers such
      as protein kinase C or phospholipase C. Although in its infancy, the use of
      inhibitors of growth factor action as antineoplastic agents has already proven
      effective against some tumours.

PMID- 1996402
TI  - Carbohydrate antigen 15-3 and mucinous carbohydrate antigen immunoreactivities in
      human seminal plasma.
AB  - Carbohydrate antigen 15-3 (CA 15-3) and mucinous carbohydrate antigen (MCA)
      immunoreactivities were detected in human seminal plasma. Mean values for CA 15-3
      (8.2 +/- 3.7 U/ml, range 2.6 - 18.4 U/ml) and MCA (13.8 +/- 8.2 U/ml, range 2.1
      31.9 U/ml) in the seminal plasma were of the same magnitude as that found in
      serum. No correlation was obtained between seminal plasma, either CA 15-3 or MCA
      immunoreactivities, and volume of seminal plasma, sperm count or percent of
      motile spermatozoa. Seminal plasma CA 15-3 and MCA levels were significantly (p
      less than 0.001) correlated (r = 0.55). The nature and origin of CA 15-3 and MCA
      immunoreactivities in human plasma are unknown.

PMID- 1996403
TI  - Sandwich assay for carcinoembryonic antigen with immobilized lectins and a
      monoclonal antibody.
AB  - A lectin-linked immunoradiometric assay (L-IRMA) using 7 different lectins and a
      monoclonal antibody (MoAb) directed against the protein moiety-specific epitope
      was developed to detect carcinoembryonic antigen (CEA). The method used for L
      IRMA was as follows: certain CEAs that reacted with lectin agarose beads were
      allowed to bind further to an 125I-labeled anti-CEA MoAb, and the resulting
      trapped 125I-MoAb was counted in a gamma counter. From the results, CEAs which
      interacted with Phaseolus vulgaris erythroagglutinin and leukoagglutinin were
      presumed to contain the complex type of sugar chains. Furthermore, CEAs
      interacting specifically with wheat germ agglutinin lectin were found in the
      tested samples, suggesting that the CEA had a hybrid or a complex type of sugar
      chain as the core structure of the sugar chain, except for that in seminal
      plasma. These results obtained by L-IRMA were in good accord with the data
      obtained from serial lectin affinity chromatography. L-IRMA may therefore be a
      simple method to study the glycoprotein heterogeneities in tumors and in normal
      subjects.

PMID- 1996404
TI  - Localization of endogenous beta-galactoside-binding lectin in human cells and
      tissues.
AB  - A rabbit antiserum raised against the 14.5-kilodalton (kDa) subunit of human
      splenic galaptin was used to probe protein blots of several tissue extracts. For
      all tissues examined, the only immunoreactive species detected was a 14.5-kDa
      polypeptide. This antiserum and a rabbit antiserum raised against native lung
      galaptin were used in immunohistochemical assays to determine the localization of
      galaptin in selected tissues and cells. In normal colon, galaptin was found
      prominently in the basement membrane and in the stroma. The cytoplasm of
      epithelial cells stained lightly for galaptin whereas mucous granules and
      secreted mucin were uniformly negative for galaptin. Hemagglutination inhibition
      assays also failed to demonstrate an interaction between galaptin and mucin.
      Macrophages stained conspicuously for galaptin in colonic and cutaneous tissue as
      did some capillary walls. In cutaneous tissue, the extracellular matrix and hair
      follicle cells contained abundant galaptin. Galaptin was absent in basal cell
      carcinoma and associated stroma. Galaptin was found throughout the cytoplasm of
      carcinoma cells of gynecologic origin present in effusions. Protein blot analysis
      of extracts of extracellular matrix synthesized in vitro by endothelial cells
      confirmed the presence of galaptin in matrix. The results show that: (1) galaptin
      is variably expressed by different cells and tissues; (2) its cellular location
      is not restricted to the cell surface; (3) galaptin is not associated with normal
      mucin; (4) the extracellular matrix is a major site of galaptin deposition, and
      (5) some malignant tissue may be characterized by a deficiency of galaptin.

PMID- 1996405
TI  - Idiotypic profile of natural autoantibodies in newborn and young adult BALB/c
      mice.
AB  - Idiotypic profiles of autoreactive monoclonal antibodies (MoAb) were evaluated by
      their reactivity with a panel of alkaline phosphatase (AP)-coupled detector MoAb
      derived from the same fusions. Attention was given to the question of whether
      differences exist between MoAb derived from spleen cells (SC) or thymocytes (TC)
      and whether ID profiles would change during post-natal development. In the
      newborn, natural autoantibodies and MoAb which did not react with any one of
      eight autoantigens displayed different ID profiles, autoreactive MoAb being
      characterized by the expression of a restricted pattern of ID. During post-natal
      development, changes of ID expression were only observed with autoreactive MoAb.
      Many ID which were detected on MoAb derived from 6-day-old mice were not detected
      on SC-derived MoAb from young adults, while a few ID were significantly over
      represented. Furthermore, especially with TC-derived MoAb, a clear linkage
      between certain idiotypes and autoantigen specificities could be demonstrated.
      Thus, in contrast to non-autoreactive MoAb, natural autoantibodies in the young
      adult were characterized by expressing only a selected number of ID at high
      frequency. Furthermore, the B-cell environment apparently played a role, since
      there were marked differences between ID profiles of TC- versus SC-derived MoAb.
      The data are interpreted in the sense that expansion and maturation of naturally
      activated autoreactive B cells are controlled rather than being random processes.

PMID- 1996406
TI  - The Nobel Lectures in Immunology. The Nobel Prize for Physiology or Medicine,
      1960. Immunologic recognition of self.

PMID- 1996407
TI  - A tumour necrosis factor beta gene polymorphism in relation to monokine secretion
      and insulin-dependent diabetes mellitus.
AB  - HLA-class III region genes may be associated with susceptibility to insulin
      dependent diabetes mellitus (IDDM). In this study an NcoI polymorphism of the
      tumour necrosis factor beta (TNF-beta) gene, which is positioned next to the
      tumour necrosis factor alpha (TNF-alpha) gene in the HLA class III region, was
      detected by restriction fragment length polymorphism (RFLP). This polymorphism
      has previously been reported to be located in the TNF-alpha gene. Caucasian HLA
      DR3,4 heterozygous IDDM patients (n = 26) and DR-matched healthy controls (n =
      19), as well as randomly selected IDDM patients (n = 27) and controls (n = 25)
      were studied. In addition four multiplex families (49 individuals) and eight HLA
      non-identical sibpairs concordant for IDDM were analysed. The TNF-beta gene RFLP
      analysis showed fragments of 5.5 kb and 10.5 kb, which behaved as alleles. In all
      groups there was a haplotype assignment of the TNF-beta 5.5-kb allele to B8,DR3
      haplotypes, and of the TNF-beta 10.5-kb allele to B15,DR4-positive haplotypes.
      The allelic and genotypic frequencies differed between DR3,4 IDDM patients and
      DR3,4 controls, and the DR3,4 control group differed significantly from the
      randomly selected control group (P less than 0.0079). In HLA-DR3,4- and DQw8
      positive persons, the DR3 haplotypes carried the 10.5-kb allele three times more
      frequently in IDDM patients than in controls, suggesting that the 10.5-kb allele
      when present on DR3 haplotypes may contribute to susceptibility to IDDM in DR3,4
      heterozygous individuals. A contributory role of the 10.5-kb allele in genetic
      IDDM susceptibility was supported by the sibpair analysis, in which all were TNF
      beta identical. Five were 10.5 kb homozygous, and the remaining three pairs were
      5.5/10.5 kb heterozygous. Twenty-five healthy and eight newly diagnosed IDDM
      patients were randomly selected to study the Escherichia coli lipopolysaccharides
      (LPS)-purified protein derivate (tuberculin) (PPD)-, and phytohaemagglutinin
      (PHA)-stimulated monocyte (Mo) secretions of interleukin 1 beta (IL-1 beta) and
      TNF-alpha in relation to the NcoI TNF-beta gene polymorphism. The LPS- and PHA
      stimulated Mo IL-1 beta and TNF-alpha secretions were significantly lower for the
      TNF-beta 5.5/10.5 kb heterozygous individuals than for TNF-beta 10.5 kb
      homozygous individuals. Furthermore, the Mo IL-1 beta and TNF-alpha secretions of
      IDDM patients were significantly higher than the Mo secretions of TNF-beta
      genotype-matched healthy controls. This study suggests an association between the
      10.5 kb TNF-beta allele and IDDM, and demonstrates an association between
      monokine responses and TNF-beta genotypes.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1996408
TI  - Lyme arthritis: oligoclonal anti-Borrelia burgdorferi IgG antibodies occur in
      joint fluid and serum.
AB  - The antibody response to Borrelia (B.) burgdorferi, and to measles virus as
      control antigen, was analysed by agarose isoelectric focusing (AIF) and
      immunoblot of joint fluid and serum from 10 patients with Lyme arthritis and 10
      controls with rheumatoid arthritis. Among the Lyme arthritis patients, six had
      oligoclonal anti-B. burgdorferi IgG antibody bands in joint fluid and
      corresponding serum, one patient had oligoclonal antibody bands in joint fluid
      only and also an elevated B. burgdorferi-specific joint fluid to serum antibody
      ratio as evidence of intra-joint production of specific antibodies, and the
      remaining three patients were negative for oligoclonal-specific antibody bands.
      Absorption with B. burgdorferi antigen confirmed the specificity of the
      oligoclonal antibody bands. They comigrated only partially on AIF with
      oligoclonal bands of total IgG, and the specificity of most oligoclonal IgG in
      joint fluid and serum in Lyme arthritis remains undefined. Among the controls, no
      anti-B, burgdorferi IgG antibodies were detected by AIF and immunoblot. Instead,
      9 of the 10 rheumatoid arthritis patients had oligoclonal anti-measles IgG
      antibody bands which were restricted to the joint fluid in three of them,
      indicating local production. We conclude that Lyme arthritis is often accompanied
      by an oligoclonal specific antibody response in joint fluid and serum
      simultaneously, and occasionally by intrasynovial synthesis of oligoclonal
      specific antibodies.

PMID- 1996410
TI  - Defective Candida opsonin and procidin function in patients with recurrent
      pyogenic infection: a common immunodeficiency.
AB  - Polymorphonuclear cell function tests were performed in 340 patients with
      recurrent unexplained infections. Serum-dependent defects in phagocytosis and
      intracellular killing of Candida albicans (Candida opsonin and procidin defects)
      were specifically associated with susceptibility to recurrent pyogenic
      infections, Candida opsonin defects occurring in 12.7% and Candida procidin
      defects in 20.8% of patients compared with 3.7% of healthy controls.
      Saccharomyces cerevisiae opsonin deficiencies were also found frequently in
      patients with recurrent infections, being present in 18.2% compared with 7.4%
      controls, although not specifically in those with pyogenic infection.

PMID- 1996409
TI  - Conglutinin binds the HIV-1 envelope glycoprotein gp 160 and inhibits its
      interaction with cell membrane CD4.
AB  - The highly glycosylated envelope glycoprotein (gp 160) of human immunodeficiency
      virus (HIV) interacts with the CD4 molecule present on the membrane of CD4+ cells
      and is involved in the pathobiology of HIV infection. Lectins bind glycoproteins
      through non-covalent interactions with specific hexose residues. The mammalian C
      type lectin bovine conglutinin was examined for its ability to interact with
      recombinant gp160 (rgp160) produced in vaccinia virus-infected BHK21 cells.
      Specific binding of conglutinin to rgp160 was demonstrated by ELISA. The
      interaction of bovine conglutinin with rgp160 was calcium-dependent, which is
      characteristic of the binding of a C-type lectin to its ligand, and the binding
      was inhibited in a dose-dependent manner with N-acetyl-D-glucosamine.
      Deglycosylation of rgp160 abrogated the conglutinin binding. In addition,
      conglutinin exerted a dose-dependent inhibition of the binding of rgp160 to the
      CD4 receptor on CEM 13 cells, as demonstrated by FACS analyses. These results
      indicate that conglutinin may inhibit the infection with HIV-1 through its
      interaction with the viral envelope glycoprotein.

PMID- 1996411
TI  - [The German-Speaking Information Commission (DIK) can offer no generally valid
      prescription. Interview by Kurt Venner].

PMID- 1996412
TI  - [The activities of the CRI. Commission Romande d'Information. Interview by Kurt
      Venner].

PMID- 1996413
TI  - ["The idea of prevention is highly regarded". Interview by Kurt Venner].

PMID- 1996414
TI  - [Dentistry in Austria. Interview by Kurt Venner].

PMID- 1996415
TI  - [In the forefront there is a forward-looking, active professional policy.
      Interview by Kurt Venner].

PMID- 1996416
TI  - [Germany: prophylaxis and prevention should be urged on the certified
      practitioner. Interview by Kurt Venner].

PMID- 1996417
TI  - [Canal obturation with the Ti-Flex cone. An in vitro trial of its tightness and
      its adaptation].
AB  - To compare, in vitro, the seal of Ti-Flex and GP cone obturations, to verify the
      adaptation of the Ti-Flex cone inside the obturated canal and to evaluate the
      density of the sealer material, eighty-two canals of freshly extracted teeth were
      manually prepared and obturated with corresponding Ti-Flex cones and with single
      GP cones. After dye infiltration the roots were transversally sectioned. On the
      first 5 apical sections (i.e. 3-5 mm from apex), the Ti-Flex obturations
      presented significantly more leakage than the GP obturations since no cones but
      only the sealer obturated these sections. The Ti-Flex cones appeared adapted to
      the walls in the apical and median segments of the canals. The density of the
      sealer in the Ti-Flex obturations was judged satisfactory in most of the
      specimens. The seal and adaptation defects of the Ti-Flex demonstrated in this
      study could be balanced by the limited effect of straightening the canal and
      thinning its dentinal wall of this anchoring system.

PMID- 1996418
TI  - [The effect of cyclosporin A (CyA) on the growth and metabolic activity of
      gingival fibroblasts].
AB  - Cyclosporine A (CyA) is a powerful nonsteroidal immunosuppressive agent in organ
      and bone marrow transplants. It may cause nephro- and hepatotoxicity and may lead
      to generalized fibrous hyperplasia of gingiva by a yet unknown mechanism. In
      order to study the pathophysiology of this side effect human gingival fibroblast
      cultures derived from normal gingiva were studied under the influence of CyA.
      During short time incubation of 72 h a significant increase of 3H-thymidine
      incorporation was noted while 14C-glucosamine incorporation remained unchanged.
      Long term incubation over 6 weeks, however, resulted in a significant increase of
      both cell proliferation and synthesis of the extracellular matrix. These findings
      demonstrate a powerful growth stimulation of gingival fibroblasts by CyA under in
      vitro conditions and show that the observed fibrous hyperplasia of the gingiva
      under CyA therapy is the result of a direct effect on gingival cells.

PMID- 1996419
TI  - [The hydrodynamic behavior of dentinal tubule fluid under occlusal loading].
AB  - In an in-vitro study, the fluid movements were quantitatively recorded in natural
      teeth incorporated rigidly in a closed measuring system and exposed to an
      occlusal load of 122.6 N. Fluid movements under load are the result of elastic
      deformations of the tooth. Occlusal loads which were repeated within a short
      period of time caused a reversible plastic deformation. In comparison to the
      unfilled tooth the placement of an MOD restoration combined with a glass ionomer
      cement base caused the following alterations in fluid movements: composite inlay 
      24.7%, ceramic inlay +34.7%, MOD amalgam -3.1%; the placement of the base per se
      induced a reduction of -12.7%. In this in-vitro study, the physical properties of
      the restorative materials governed the magnitude of the fluid movements under
      load. The results are in contradiction to clinical findings and favor the
      pulpitis-related genesis of postoperative sensitivity. The intratubular and
      intrapulpal fluid movements under occlusal load simply seem to trigger the pain
      sensation.

PMID- 1996420
TI  - [Tooth developmental disorders. Developmental disorders in the permanent teeth].

PMID- 1996421
TI  - [Traumatology in the deciduous dentition (II). The long-term results and effects
      on the deciduous and permanent dentition].

PMID- 1996422
TI  - [Semipermanent splinting. The blocking of severely loosened and dislocated teeth
      with fiberglass-reinforced plastic].

PMID- 1996423
TI  - [The tasks of the Economics Commission. Interview by Kurt Venner].

PMID- 1996424
TI  - [Contact with the mass media should be intensified. Interview by Kurt Venner].

PMID- 1996425
TI  - Single photon emission computed tomography imaging of brain tumors.
AB  - Five radiotracers may be used for single-photon emission computed tomography
      (SPECT) imaging of brain tumors, namely technetium 99m pertechnetate, iodine-123
      amphetamine derivatives, 99mTc-hexamethyl propylene amine oxime (HMPAO), thallium
      201, and 123I alpha methyl tyrosine. Of these, pertechnetate may be considered as
      an "historical" procedure in brain tumors. However, there may be some equivocal
      cases in computed tomography or magnetic resonance imaging, where this procedure
      may still be used. In 1981, 123I isopropyl amphetamine was first used in brain
      tumors. Further studies showed, however, that IMP is not a useful tool for brain
      imaging in tumorous lesions. In 1986, 99mTc HMPAO appeared on the European market
      as a new tumor imaging agent. Some useful clinical results were obtained in
      patients before and after chemotherapy or radiotherapy. Thallium-201 was
      incidentally noted to accumulate in tumors. Using a threshold index, this agent
      can be used to distinguish low-versus high-grade lesions. The most promising
      agent for brain tumor SPECT is 123I-alpha methyl tyrosine, which shows potential
      to evaluate therapeutic procedures in brain tumors and may improve the
      differentiation between abscess and glioblastoma. The most promising aspect is
      the differentiation of tumor recurrences and scar tissue after brain surgery.

PMID- 1996426
TI  - Functional brain imaging in the evaluation of psychiatric illness.
AB  - In the past century, the field of psychiatry has undergone major changes. During
      this time, significant advancements in both diagnosis and treatment have
      occurred. Medical brain imaging using structural and functional brain imaging
      techniques have contributed, in part, to a better basic understanding of
      psychiatric disease and to an improving diagnostic approach. Computed tomography
      and magnetic resonance imaging have supplied limited, but useful insight
      regarding structural alterations in schizophrenia and the affective disorders.
      Position emission tomography imaging has already made a major contribution in the
      assessment of schizophrenia and affective disorders. Single-photon emission
      computed tomography (SPECT), which is currently more widely available, should
      contribute more to psychiatric disease evaluation in the future. Recent advances
      in SPECT technology in the areas of improved instrumentation--such as
      multidetector and ring detector systems and new radiopharmaceuticals including
      new rCBF markers and receptor site imaging agents--have contributed to
      significant improvements in the SPECT imaging technique. At the present time,
      SPECT has been shown to be feasible and useful in the evaluation of acute and
      chronic psychiatric and demented states. As SPECT technology continues to evolve,
      further refinements in this diagnostic capability can be anticipated.

PMID- 1996427
TI  - Brain single photon emission computed tomography: newer activation and
      intervention studies.
AB  - Single-photon emission computed tomography (SPECT) regional cerebral blood flow
      (rCBF) findings using non-xenon 133 tracers in combination with activation and
      intervention techniques are reviewed. Examination of the currently available data
      indicates that it is possible to detect the effects of a variety of activations
      and interventional procedures using SPECT rCBF with non-xenon 133 tracers. There
      are still many issues to be resolved before SPECT can reach the level of
      sophistication attained by xenon 133 and positron emission tomography in studying
      rCBF during activation or intervention. However, research to date indicates that
      SPECT rCBF studied with tracers other than xenon 133 has an excellent potential
      for increasing the ability to differentiate normal and pathological states.

PMID- 1996428
TI  - Studies of central nervous system disorders with single photon emission computed
      tomography and positron emission tomography: evolution over the past 2 decades.
AB  - Single photon emission computed tomography (SPECT) was introduced in the 1960s to
      detect breakdowns in the blood-brain barrier and was replaced by x-ray computed
      tomography in the mid-1970s. The development of the deoxyglucose (DG) technique
      to measure regional cerebral glucose metabolism by employing either
      autoradiography, using 14CDG, or positron emission tomography (PET), using 18FDG,
      added a major dimension to the investigation of brain function. In the late 1970s
      and early 1980s, the FDG-PET technique was widely used to examine a variety of
      neuropsychiatric disorders. It soon became apparent that functional imaging was
      more sensitive than anatomic imaging in detecting abnormalities of the brain
      related to aging, dementia, tumors, seizures, cerebral vascular accidents, and
      psychiatric problems. Because of its complexity and the cost involved, PET was
      used in a limited number of centers in the United States. However, the success of
      PET resulted in the resurgence of interest in SPECT as an alternative technology
      after almost a decade. This became possible because of the synthesis of iodine
      123- and technetium 99m-labeled radiopharmaceuticals to determine regional
      cerebral blood flow. Since blood flow and metabolism are coupled in most
      pathological states, patterns of abnormality noted on SPECT were similar to those
      seen on PET in many disorders. Since the introduction of high resolution SPECT
      imaging instruments, the role of SPECT has been further enhanced. The successful
      synthesis of both positron and single emitting radioligands to image dopamine and
      other receptors has started a new era in neurosciences and will have a far
      reaching impact on the day-to-day practice of neuropsychiatry.

PMID- 1996429
TI  - Techniques for radioactive decontamination in nuclear medicine.
AB  - Working with unsealed radioactive sources in nuclear medicine carries the
      potential risk of contamination. Careful design of a department and its
      operational procedures will minimize but never completely eliminate the
      possibility of such incidents occurring. Contingency planning forms as important
      a part of handling such incidents as the procedures to reduce the hazard once an
      incident has occurred. It should include anticipating where such incidents are
      likely to occur, training and exercising staff in the appropriate procedures to
      deal with these incidents, providing a comprehensive decontamination kit, and
      implementing a routine contamination monitoring survey. Assessing the magnitude
      of the radiation hazard and the effect of decontamination efforts, containing the
      spread of contamination, minimizing the radiation dose to individuals, and
      continuing to decontaminate to the lowest level possible are principles to follow
      in managing any incident. Nuclear medicine staff should be familiar with
      techniques for decontaminating different anatomical sites on the body; for
      eliminating or reducing the uptake of radioactivity absorbed into the body; and
      for decontaminating dry and wet surfaces, equipment, clothing, and bedding.
      Radiopharmaceutical dispensing procedures, ventilation scanning, and
      decontaminating 131I treatment areas are identified as the most likely causes of
      body surface and internal contamination of nuclear medicine staff.

PMID- 1996430
TI  - RSA could be spared the full effect of AIDS.

PMID- 1996431
TI  - Poliomyelitis--countdown to eradication.

PMID- 1996432
TI  - Should AIDS be made notifiable?

PMID- 1996434
TI  - Exercise-related cardiac arrest in cardiac rehabilitation. The Johannesburg
      experience.
AB  - Prescribed physical activity plays a major role in the rehabilitation of patients
      with coronary artery disease, and as with any other form of treatment its
      benefits must be weighed against its possible risks. This study attempted to
      establish the safety of cardiac rehabilitation as a medical intervention at the
      Johannesburg Cardiac Rehabilitation Centre from its inception in September 1982
      to July 1988, and analyses the medical status of patients who suffered a cardiac
      arrest (CA) in order to determine possible factors predictive of sudden death.
      Between September 1982 and July 1988, 1,574 patients were admitted to the unit;
      480,000 man-hours of exercises were accumulated with 4 episodes of CA, giving an
      incidence of CA of 1/120,000 patient-hours. Three of the 4 episodes were fatal,
      giving an incidence of fatal CA of 1/160,000 patient-hours. This incidence is
      acceptably low and comparable with other cardiac rehabilitation programmes,
      making exercise as prescribed at the Johannesburg Cardiac Rehabilitation Centre a
      safe form of medical intervention. Patients at risk of CA during exercise were
      essentially not identifiable, since they did not come from a group currently
      recognised as at particularly high risk. A combination of inferior infarction
      with occluded dominant right coronary artery, good collateralisation and
      asymptomatic ischaemia was present in all CA patients. The likelihood of these
      pathological features being predictors of exercise-related sudden death requires
      further investigation.

PMID- 1996433
TI  - The Johannesburg cardiac rehabilitation programme.
AB  - Cardiac rehabilitation has become a generally accepted mode of treatment for
      patients suffering from coronary artery disease. The Johannesburg cardiac
      rehabilitation programme was started in 1982 and has rapidly grown to become one
      of the largest programmes in southern Africa. This paper describes the 387
      patients admitted to the unit between June 1986 and July 1988 and evaluates the
      effects of a combined exercise training and lifestyle modification programme. The
      mean age on admission was 55 years for males and 58 years for females. Most
      patients were from social classes I and II. Myocardial infarction, coronary
      artery bypass graft and a combination of both were the most common reasons for
      admission (35.4%, 23% and 21.2% respectively). On admission 72.9% of patients
      were smokers, 26.3% had hypertension and 34.3% had hypercholesterolaemia. A 50%
      drop-out rate within 12 months of starting the programme was noted. An increase
      in peak oxygen uptake, weight and skinfold thickness reduction, and improvement
      in the lipogram were seen after 6 months in patients who complied well with the
      programme. Cardiac rehabilitation is a secondary preventive strategy that can
      complement traditional medical and surgical therapies.

PMID- 1996435
TI  - The effect of nifedipine on fetal umbilical artery Doppler waveforms in
      pregnancies complicated by hypertension.
AB  - The effect of nifedipine 5 mg administered sublingually to pregnant hypertensive
      patients was examined in a randomised controlled double-blind study. The effect
      on maternal blood pressure and the fetal umbilical artery Doppler waveform was
      studied for 30 minutes before and 30 minutes after administration of the drug or
      placebo. This dose resulted in a significant drop in maternal blood pressure 30
      minutes after administration and did not result in a significant change in the
      Doppler umbilical artery waveform (in fetuses with normal waveforms) when
      compared with a control group.

PMID- 1996436
TI  - Iron dextran in the treatment of iron-deficiency anaemia of pregnancy.
      Haematological response and incidence of side-effects.
AB  - Sixty pregnant patients with a haemoglobin (Hb) less than 8 g/dl and proven iron
      deficiency anaemia were randomly allocated to two treatment groups. Group A
      received the usual recommended dose of iron dextran (Imferon; Fisons) and group B
      received two-thirds of the recommended dose. A further 30 patients received oral
      iron (group C). There was no difference in Hb value between the three groups 4
      weeks after treatment or 3 months after delivery. At 6 months after delivery, a
      higher mean Hb value was found in the patients in group A than those in groups B
      and C. Significantly higher serum ferritin levels were found in group A and this
      difference was still present 6 months postnatally. There was no significant
      difference in the incidence of delayed reactions between the two groups who
      received iron dextran.

PMID- 1996437
TI  - Comparison between umbilical artery and vein endogenous digoxin-like immuno
      active factor levels in normal and pre-eclamptic patients.
AB  - Recent studies have pointed to the existence of an endogenous digoxin-like immuno
      active factor (DLIF), which may be associated with hypertension and pre
      eclampsia. The DLIF levels in the umbilical venous and umbilical arterial blood
      of neonates, as well as the maternal serum of primigravidas and multigravidas
      with and without pre-eclampsia, were determined by means of a commercially
      available radioimmunoassay kit, which is cross-reactive with DLIF, in 44 mothers
      and their babies in search for a possible placental, fetal or maternal origin of
      the DLIF. The mean placental and neonatal masses were significantly lower in the
      pre-eclampsia group than in the control group (P less than 0.01). However, the
      DLIF levels in the maternal serum, umbilical cord venous and umbilical cord
      arterial serum were statistically significantly higher in the pre-eclampsia group
      than in the control pregnant group (P less than 0.05). A very strong correlation
      was found between umbilical cord venous and arterial DLIF levels (r = 0.90; P =
      0.001, Spearman rank-correlation coefficient). Although the mean DLIF level in
      cord arterial serum was lower than that of cord venous serum, statistical
      significance was not reached if the Bonferroni adjustment was applied to the P
      value.

PMID- 1996438
TI  - Intertrochanteric and femoral neck fractures in patients with parkinsonism.
AB  - Thirty-eight patients with parkinsonism were reviewed after fracture of the hip.
      The 12-month mortality rate was the same as in other patients with hip fractures
      but without parkinsonism. However, the morbidity was higher-with loss of
      independent existence, loss of ambulation and an increased risk of dislocation of
      the endoprosthesis.

PMID- 1996439
TI  - 'Pathological' fracture of the femur--a complication of failed total hip
      arthroplasty.
AB  - Ten patients with a major femur fracture complicating total hip arthroplasty were
      seen at the Princess Alice Orthopaedic Hospital between June 1986 and May 1988.
      Four cases were intra-operative fractures sustained at revision surgery and 6
      were late postoperative fractures of the femur associated with minimal trauma.
      Eight patients have a pain-free and functional hip arthroplasty at a mean follow
      up of 19.7 months (range 17-32 months). One patient developed deep sepsis and 1
      persistent non-union: both are now well mobilised following excision
      arthroplasty. Predisposing factors are identified and the importance of timeous
      intervention to avoid this challenging complication is stressed.

PMID- 1996440
TI  - Operative fixation of fractures in children.
AB  - A total of 39 fractures of the diaphyses of long bones in 31 children were
      subjected to operative fixation. Indications for surgery included concomitant
      severe head injury, multiple injuries, patients nearing skeletal maturity,
      inability to obtain a satisfactory reduction by conservative means, severe soft
      tissue injury with or without vascular trauma, long-standing neurological
      disorder with incapacity and contractures, malunion, and delayed union. Although
      long-bone diaphyseal fractures in children are generally managed non-operatively,
      the use of fixation may be indicated in certain cases.

PMID- 1996441
TI  - Phaeochromocytoma. A report of 10 patients.
AB  - A spectrum of presentation of phaeochromocytoma in black South Africans is
      described. Ten patients were reviewed over a 9-year period. Sweating, headache,
      and palpitations were prominent symptoms in 9 patients; postural dizziness
      occurred in 5; gastro-intestinal symptoms in 7; diabetes in 3; and hypertension
      in all. One patient developed a phaeochromocytoma crisis, characterised by
      hypotension and pulmonary oedema, before operation. One woman presented in
      pregnancy. Urinary vanillylmandelic acid was elevated in 9 out of 10 subjects
      tested; plasma catecholamines were elevated in 6 out of 6 tested. Computed
      tomography detected 7 adrenal tumours and 3 paragangliomas. All patients were
      stabilised pre-operatively with alpha- and/or beta-receptor blockers.
      Intraoperative pressor crises were controlled with sodium nitroprusside,
      phentolamine, or magnesium sulphate infusions. At operation all tumours appeared
      benign, each was successfully removed, and the diagnosis confirmed on
      histological examination. There was no operative mortality. Two patients had
      residual hypertension. This study highlights the various challenges presented by
      this catecholamine-producing tumour.

PMID- 1996443
TI  - AIDS--a need for uniform terminology.

PMID- 1996442
TI  - Intermittent intravalvar regurgitation of a mechanical aortic valve prosthesis-
      diagnosis and clinical implications. A case report.
AB  - Mechanical prosthetic valve regurgitation may be either periprosthetic or
      intraprosthetic. The latter is usually mild, occurring in the majority of
      normally functioning valves and is due to the 'regurgitant flow' closing the
      valve. An unusual case is reported of intermittent intraprosthetic regurgitation
      through a normally functioning aortic Medtronic-Hall prosthesis caused by tissue
      ingrowth below the valve 4 years after implantation.

PMID- 1996444
TI  - Examination of the bone marrow in severely septic patients with neutropenia.

PMID- 1996445
TI  - Blood-brain barrier alteration after microwave-induced hyperthermia is purely a
      thermal effect: I. Temperature and power measurements.
AB  - The effect of microwave-induced hyperthermia on the blood-brain barrier was
      studied in 21 Sprague-Dawley rats. Under sodium pentobarbital anesthesia, animals
      were place in a stereotactic frame, and an interstitial microwave antenna
      operating at 2450 MHz was inserted in a bony groove drilled parallel to the
      sagittal suture. Some antennae were equipped with an external cooling jacket.
      Temperature measurements were made lateral to the antenna by fluoroptical
      thermometry, and power was calculated from the time-temperature profile. Five
      minutes prior to termination of microwave irradiation, horseradish peroxidase (1
      mg/20 g body weight) was injected intravenously. Extravasation of horseradish
      peroxidase was observed in brain tissue heated above 44.3 degrees C for 30
      minutes and at 42.5 degrees C for 60 minutes. Microwave irradiation failed to
      open the blood-brain barrier when brain temperatures were sustained below 40.3
      degrees C by the cooling system. Extravasation of blood-borne peroxidase occurred
      at sites of maximal temperature elevation, even when these did not coincide with
      the site of maximum power density. The data suggest that microwave-induced
      hyperthermia is an effective means for opening the blood-brain barrier and that
      the mechanism is not related to the nonthermal effect of microwaves.

PMID- 1996446
TI  - Quantification of midline shift as a predictor of poor outcome following head
      injury.
AB  - A retrospective study of patient outcome, based on admission computed tomography,
      was carried out in 75 consecutive patients with head injury. Computed tomography
      data collected included the type and extent of intracranial hemorrhage, the
      extent of midline shift, and the ratio of midline shift compared with the extent
      of intracranial hemorrhage. Midline shift was considered to be out of proportion
      to intracranial hemorrhage when the midline shift of the septum pellucidum
      exceeded the extent of the hemorrhage as measured radially from the inner table
      of the skull. When computed tomography data were analyzed by logistic regression,
      significant predictive factors for poor outcome were intracranial hemorrhage
      (34%), intracranial hemorrhage with midline shift (61%), and midline shift out of
      proportion to the extent of intracranial hemorrhage (88%). When patient outcome
      and mortality rates are considered, our study indicates that midline shift out of
      proportion to the extent of intracranial hemorrhage is a highly useful predictor
      of poor patient outcome following head injury.

PMID- 1996447
TI  - Tumoral thrombosis of cerebral venous sinuses: preoperative diagnosis using
      magnetic resonance phase imaging.
AB  - Intracranial, dural-based neoplasms will not infrequently invade adjacent venous
      sinuses. Therefore, the preoperative diagnosis of venous invasion is important,
      as it will alter the surgical approach to the lesion. Magnetic resonance imaging
      is a noninvasive means of visualizing the cerebral venous sinuses. The
      preoperative diagnosis of venous thrombosis can, however, be difficult and
      confusing with conventional spin-echo magnetic resonance imaging because of
      variable appearances produced by blood clot degradation products as well as
      flowing blood. Phase magnetic resonance imaging is a simple method that can be
      acquired simultaneously with conventional spin-echo sequences, and is based
      primarily on whether protons are stationary or moving. In the context of venous
      sinus occlusion, phase imaging can demonstrate the presence or absence of blood
      flow more easily than spin-echo imaging. Three cases of dural-based neoplasms are
      presented that demonstrate the utility of phase imaging in diagnosing tumoral
      occlusion of the venous sinuses.

PMID- 1996448
TI  - America's health care system: what's coming next?

PMID- 1996449
TI  - Hydrocephalus: overdrainage by ventricular shunts. A review and recommendations.
AB  - Selected literature review of the clinical course of patients with ventricular
      shunts for hydrocephalus shows that the effects of cerebrospinal fluid
      overdrainage are subdural hematoma, craniosynostosis, slit ventricle syndrome,
      and low intracranial pressure syndrome. These occur sequentially at different age
      groups, but approximate averages of incidence and time of occurrence after first
      shunt reveal an overall incidence of 10%-12% for at least one of these appearing
      at 6.5 years after shunting. The basic etiology, diagnosis, and variety of
      treatment modalities available are reviewed, including the need for shunt closing
      intracranial pressure control. Included is a hydrocephalus program designed to
      minimize the need for long-term extracranial shunts and to maximize therapeutic
      intracranial procedures for hydrocephalus.

PMID- 1996450
TI  - Unusually late onset of cerebrospinal fluid rhinorrhea after head trauma.
AB  - Two cases of acute meningitis and cerebrospinal fluid rhinorrhea, in which the
      head trauma responsible occurred 10 and 30 years before, are presented.
      Intraoperatively, the brain parenchyma was found to be plugged into the fractured
      anterior fossa. By debridement and duraplasty from an intradural approach, both
      patients were cured. Several precipitating factors could be responsible for this
      unusually late reopening of the fistula. The possible accidental causes could be
      coughing or undetected microtraumas, but in the long run, atrophy of tissues and
      consequent changes in brain compliance with aging may play a role.

PMID- 1996452
TI  - Anterior communicating artery aneurysm in early childhood. Report of a case.
AB  - A case of an aneurysm of the anterior communicating artery in a 13-month-old
      child is presented. Sixty-six cases of cerebral saccular aneurysm in children
      under the age of 2 years found in the literature were analyzed. The
      characteristics that define this group of patients are a high frequency of large
      or giant aneurysms, a large proportion of aneurysms of the middle cerebral artery
      and the posterior circulation, and the frequent location at the peripheral site.
      Only three cases of anterior communicating artery aneurysm were reported in the
      literature. The authors discuss these characteristics on the basis of development
      of fetal cerebral vessels.

PMID- 1996451
TI  - Angiotropic intravascular large-cell lymphoma (malignant angioendotheliomatosis):
      report of a case and review of the literature.
AB  - We present a case of angiotropic large-cell lymphoma and review the literature in
      order to define the neurologic features of this rare disorder. This is the first
      report of gadolinium-DTPA imaging in angiotropic large-cell lymphoma that
      demonstrates infarcts of multiple ages, as well as striking meningeal
      enhancement. Angiotropic large-cell lymphoma should be suspected in patients with
      clinical evidence of small and large cerebral vessel disease and diagnosis
      requires skin, liver, renal, meningeal, or brain biopsy. Single modality
      treatment, using either radiation therapy or steroids, has been ineffective, and
      new findings of a lymphomatous origin of this neoplasm suggest that combination
      chemotherapy may be indicated.

PMID- 1996453
TI  - Intracranial chordoma in a preadolescent. Case report.
AB  - Chordomas are rare tumors derived from notochord remnants occurring primarily in
      the sacrum, clivus, and cervical regions. Exceptionally, these tumors occur in
      children, though usually in the sacrum. Eight cases of clivus chordoma have been
      described in preteenagers. In this report, a clival chordoma with unusual
      radiologic features is described in an 11-year-old boy. The literature regarding
      this entity is reviewed.

PMID- 1996454
TI  - Solitary, isolated metastasis from Ewing's sarcoma to the brain: case report.
AB  - We report a case of a 30-year-old woman who developed an intraparenchymal
      cerebral metastasis from a Ewing's sarcoma of the chest wall diagnosed and
      treated 3 years earlier and in apparent remission at the time of the neurological
      presentation (seizures). The case was complicated by a spontaneous preoperative
      intratumoral hemorrhage that occurred the morning of the scheduled surgical
      resection and caused a left dense hemiparesis. The tumor and the hematoma were
      removed. The patient improved after surgical intervention and a postoperative
      course of cranial irradiation followed by systemic chemotherapy was given.
      Nineteen months after treatment the patient remains disease-free from the
      clinical and radiological standpoint.

PMID- 1996455
TI  - Treatment of leptomeningeal carcinomatosis with continuous intraventricular
      infusion of recombinant interleukin-2.
AB  - A 42-year-old man developed leptomeningeal carcinomatosis 6 years after treatment
      of a malignant melanoma. He was treated with two courses of recombinant
      interleukin-2, administered as a continuous intraventricular infusion (6 X 10E5
      U/24 h) during 5 days. During the first day of the first course he also received
      5 X 10E9 lymphokine-activated killer cells intraventricularly. This gave rise to
      a severe elevation of intracranial pressure, with headaches and meningismus.
      During the second course no LAK cells were administered. This course was
      tolerated much better. The neurological status did not change during the
      treatment. Recombinant interleukin-2 levels were maintained at about 300 U/mL
      during both courses.

PMID- 1996456
TI  - The neurological complications of cardiac transplantation.

PMID- 1996457
TI  - Central Surgical Association. The first fifty years 1941-1991.

PMID- 1996458
TI  - [The legality of the Code].

PMID- 1996459
TI  - [The usefulness of urine analysis for the diagnosis of macroscopic lesions of the
      urogenital system of sows during slaughter].
AB  - As part of a research project concerned with the monitoring of health problems in
      sows, the practicability of post-mortem urinalysis of sows during slaughter was
      studied to determine the extent to which this analysis was useful. Samples of
      urine were taken from 232 sows after slaughter to test them for pH, nitrite and
      blood concentrations by test strips (Combur-8, Boehringer Mannheim). Positive
      results of testing were found not to be associated with pathological disorders of
      the genito-urinary system to any marked extent. Samples of urine taken pre- as
      well as post-mortem from 111 other sows were subjected to same tests. During the
      process of slaughter, the pH was found to show a decrease, whereas the
      concentrations of protein and blood increased. The results of post-mortem tests
      for nitrite were definitely not correlated with those of pre-mortem tests. The
      results of testing urine sampled prior to slaughter at the farm were related to
      post-mortem pathological findings to a greater extent than were the results of
      testing after slaughter.

PMID- 1996461
TI  - [Veterinary practice and the environment: what to do and what to omit].
AB  - A veterinary practice supplies services and goods, both sections involving acts
      affecting the environment. Until recently, little attention was paid to the
      environment, but today far more is known concerning the manner in which
      veterinary practices should handle the environment. Among other things, this
      paper will be concerned with the groups of various substances which constitute a
      menace to the environment, the relevant environmental policy as well as the
      approach to environmental policy in practice and to the function of the
      veterinary surgeon as distributor of veterinary drugs respectively. Instruction
      of the users of veterinary drugs as regards storage and exposure to pollution are
      discussed. Finally, the economic aspects of a modern environmental policy in
      veterinary practice are referred to.

PMID- 1996460
TI  - [A horse seropositive for Ehrlichia risticii].
AB  - A four year old Dutch warmblooded mare was born and raised in the province of
      North-Brabant, the Netherlands. On May 16, 1989, she showed signs of colic,
      anorexia, depression, ileus, severe dehydration and leukopenia. When the mare
      collapsed, euthanasia was carried out. Acute colitis and cytoplasmic inclusion
      bodies in macrophages were observed at autopsy. When an indirect
      immunofluorescence assay was performed, the Ehrlichia risticii titre of the serum
      was found to be 1:640.

PMID- 1996462
TI  - [Drastic measures in urea determinations].

PMID- 1996463
TI  - Methods for in vitro skin absorption studies of a lipophilic toxin produced by
      red tide.
AB  - The penetration and distribution of [3H]PbTx-3 into pig skin was determined using
      in vivo and in vitro methods. The dose used in each topical study was 0.3-0.4
      micrograms/cm2 skin, with dimethylsulfoxide as the vehicle. In the in vivo study,
      mean cutaneous absorption after 48 h (expressed as percentage of the dose) was
      11.5% (n = 3). In the in vitro study, mean cutaneous absorption after 48 h was
      1.6% (n = 12), when based on accumulation of radioactivity in receptor fluid, or
      9.9% when based on receptor fluid and dermis. [3H]PbTx-3 readily penetrated
      through the epidermis into the dermis, reaching maximal dermal accumulation at 4
      h (9.1% in vivo and 18% in vitro). At 24 h, the amount in the dermis decreased to
      2.3% and 15% in vivo and in vitro, respectively and at 48 h the amount in the
      dermis decreased to 8.2% in vitro. These results demonstrate the important role
      of the dermis as a reservoir for a lipophilic compound in both in vivo and in
      vitro percutaneous absorption studies.

PMID- 1996464
TI  - Time course of testicular degeneration in rats induced by a synthetic retinoid
      (Ro 23-2895) and evidence for induction of hypovitaminosis A in the testes.
AB  - Eight-week-old male Sprague--Dawley rats were dosed by gavage with 90 mg/kg of Ro
      23-2895, (all-E)-9-[2-(nonyloxy)phenyl]-2,4,6,8 nonatetraenoic acid, dissolved in
      Tween 80. Treated animals (n = 3--4) were sacrificed after 3, 7, 11 and 21 days
      of dosing. Control rats (n = 3) received an equal volume of Tween 80 and were
      sacrificed after 3 or 21 days. Cross sections of formalin fixed testes were
      embedded in glycolmethacrylate, sectioned at 3 microns, and stained with periodic
      acid-Schiff and hematoxylin. No morphologic alterations were observed in the
      control rats or in treated rats after 3 days. After 7 days of treatment, there
      were occasional tubules in which there was a delayed release of mature sperm and
      occasionally the retained sperm were being resorbed. The frequency and severity
      of these morphologic changes was increased after 11 days of treatment, and round
      spermatids were occasionally observed with marginated chromatin in their nuclei.
      After 21 days of treatment, there was a significant reduction in testicular
      weight accompanied by marked degenerative changes and in some cases almost a
      complete desquamation of the germinal epithelium. Multinucleated giant cells and
      germ cells with marginated chromatin in their nuclei were commonly observed and
      there was moderate to severe oligospermia in the tubules. Sertoli cell nuclei
      were swollen and showed lucent, vesiculated nucleoplasm. In a parallel 21-day
      study, treated rats (n = 10) showed an 80% reduction in plasma retinol and a 56%
      decrease in testicular retinol compared to vehicle-treated rats (n = 10). A 53%
      decrease in plasma testosterone levels was also observed in treated rats. The
      testicular lesions produced by treatment with Ro 23-2895 were similar to vitamin
      A deficiency, which supports the hypothesis that high doses of synthetic
      retinoids may cause testicular degeneration through interference of normal
      retinol homeostasis.

PMID- 1996465
TI  - Effect of calcium antagonism by nifedipine and chlorpromazine on acute N-(3,5
      dichlorophenyl)succinimide-induced nephrotoxicity in Fischer 344 rats.
AB  - The nephrotoxicity induced by a wide variety of chemical compounds can be
      attenuated by agents which modify calcium ion (Ca2+) movement across membranes or
      calcium-dependent processes. The purpose of this study was to examine the ability
      of nifedipine, a calcium channel blocking drug, and chlorpromazine (CPZ), an
      antagonist of many calcium-dependent processes, to attenuate the nephrotoxicity
      induced by the agricultural fungicide N-(3,5-dichlorophenyl)succinimide (NDPS) or
      its metabolite N-(3,5-dichlorophenyl)-2-hydroxysuccinimide (NDHS). Male Fischer
      344 rats (4 rats per group) were pretreated intraperitoneally (i.p.) with
      nifedipine (0.25 or 0.50 mg/kg), CPZ (1.0 or 5.0 mg/kg) or vehicle 1 h before
      NDPS (0.4 mmol/kg), NDHS (0.1 mmol/kg) or vehicle (sesame oil, 2.5 ml/kg). In
      separate experiments, rats were pretreated with nifedipine (0.25 or 0.50
      mg/kg/day, i.p.) starting 2 days before NDPS or NDPS vehicle and continuing
      throughout the experiment. Renal function was monitored at 24 and 48 h.
      Nifedipine (single or multiple treatments) and CPZ (1.0 mg/kg) were ineffective
      in substantially altering NDPS (0.4 mmol/kg)-induced nephrotoxicity. However, CPZ
      (5.0 mg/kg) markedly attenuated all aspects of NDPS-induced nephropathy. Also,
      CPZ (5.0 mg/kg) partially protected against NDHS (0.1 mmol/kg)-induced renal
      effects. These results demonstrate the inability of the calcium channel blocker
      nifedipine to attenuate NDPS nephrotoxicity. Attenuation of NDPS nephrotoxicity
      by CPZ could suggest that CPZ is antagonizing calcium influx into renal tissue
      and/or renal intracellular calcium-dependent processes to modify the renal
      response to NDPS. However, the inability of CPZ to markedly attenuate NDHS
      nephrotoxicity could indicate that CPZ protected against NDPS nephrotoxicity by
      inhibiting biotransformation of the parent compound to its toxic chemical
      species.

PMID- 1996466
TI  - Effect of sodium butyrate on metallothionein induction and cadmium cytotoxicity
      in ROS 17/2.8 cells.
AB  - ROS 17/2.8 cells, a cloned rat osteosarcoma cell line, are exceptionally
      sensitive to the cytotoxic effects of cadmium. This sensitivity is associated
      with the inability of this metal to induce the synthesis of metallothionein, a
      transition metal-binding protein, which detoxifies this metal by its
      sequestration. Sodium butyrate induces the synthesis of metallothionein in these
      cells in a concentration-dependent manner. Treatment with this agent also
      significantly increases the resistance of these cells to the cytotoxic effects of
      cadmium and the protective effect of butyrate is reversed upon its removal from
      culture medium. Butyrate treatment did not significantly alter the accumulation
      of cadmium by these cells. Hence, the increased synthesis of metallothionein in
      butyrate-treated cells is not due to increased cellular uptake of cadmium.
      Inhibition of DNA synthesis due to butyrate was not a sufficient condition to
      alter metallothionein synthesis or to protect against Cd-induced cytotoxicity.
      Equivalent inhibition of DNA synthesis with hydroxyurea failed to increase
      metallothionein synthesis in cadmium-treated cells. These results indicate that
      modulation of metallothionein gene expression in this cell line is the critical
      factor in determining cellular sensitivity to the cytotoxic effects of cadmium.

PMID- 1996467
TI  - Interactions among nephrotoxicants: N-(3,5-dichlorophenyl)succinimide and
      cephaloridine.
AB  - Numerous studies have demonstrated the interactive potential between
      nephrotoxicants. The purpose of this study was to examine the interactive
      potential between two model nephrotoxicants, N-(3,5-dichlorophenyl)succinimide
      (NDPS) and cephaloridine (CPH). Male Fischer 344 rats (4 rats per group) were
      administered an intraperitoneal (i.p.) injection of CPH (500 mg/kg), NDPS (0.2
      mmol/kg) or the appropriate vehicle 1 h prior to administration of an i.p.
      injection of NDPS (0.2, 0.4, or 1.0 mmol/kg), CPH (500, 750 or 1000 mg/kg) or the
      appropriate vehicle. Renal function was monitored at 24 and 48 h. Combination of
      non-nephrotoxic doses of CPH (500 mg/kg) and NDPS (0.2 mmol/kg) did not result in
      nephrotoxicity, regardless of which compound was administered first. NDPS (0.2
      mmol/kg) weakly enhanced the nephrotoxicity observed following CPH (1000 mg/kg)
      injection but had little effect on CPH (750 mg/kg)-induced renal effects.
      However, CPH (500 mg/kg) markedly attenuated NDPS (0.4 or 1.0 mmol/kg)-induced
      nephrotoxicity. These results demonstrate that prior NDPS exposure has little
      effect on the outcome of CPH-induced renal effects, but prior CPH exposure can
      markedly alter the renal response to NDPS administration.

PMID- 1996468
TI  - Vanadate-induced toxicity towards isolated perfused rat livers: the role of lipid
      peroxidation.
AB  - The toxic potential of sodium orthovanadate towards isolated perfused rat livers
      was investigated at a dose of 2 mmol/l. In livers from fasted rats, vanadate led
      to a release of cytosolic (glutamate-pyruvate-transaminase (GPT) and lactate
      dehydrogenase (LDH] and mitochondrial (glutamate dehydrogenase (GLDH] enzymes, an
      accumulation of calcium in the liver, a marked depletion of hepatic glutathione
      and an enhanced release of it into the perfusate, as well as an augmented
      formation and release of thiobarbituric acid-reactive material by the liver.
      Furthermore, a marked inhibition of oxygen consumption was observed. Vanadate
      induced vasoconstriction resulted in a progressive decrease in perfusate flow
      rate. Control experiments with similarly reduced flow rates led to a comparable
      reduction in oxygen consumption. GPT and LDH release and hepatic glutathione
      depletion were also evident, though to a lesser extent than in the presence of
      vanadate, but no increase in GLDH release, in tissue calcium content or TBA
      reactive material in the liver or the perfusate were observed. Thus, indirect
      toxic effects due to a reduced flow rate contribute only partly to vanadate
      hepatotoxicity and do not affect mitochondrial integrity. Omission of calcium
      from the perfusate did not prevent hepatotoxic responses to vanadate, although
      less calcium was present in the treated livers than in the control organs,
      indicating that calcium influx is not involved in vanadate-induced hepatotoxicity
      in the intact organ, in contrast to isolated hepatocytes. Feeding the animals,
      resulting in an activation of anaerobic energy conservation reactions, strongly
      attenuated vanadate hepatotoxicity indicating that the energetic status of the
      liver is the main target of vanadate. Superoxide dismutase did not affect the
      hepatotoxic responses of livers from fasted rats towards vanadate, while
      allopurinol and deferrioxamine inhibited lipid peroxidation and hepatotoxicity
      due to vanadate. The strong correlation between induction of lipid peroxidation
      and hepatotoxicity and the inhibition of both processes in parallel by
      antioxidants are suggestive of a causative role for lipid peroxidation in
      vanadate-induced hepatotoxicity.

PMID- 1996470
TI  - Distribution of terbium and increase in calcium concentrations in organs of mice
      administered with terbium chloride.
AB  - To investigate the biological effects of terbium (Tb), male mice were
      intraperitoneally administered with TbCl3 at doses of 10, 50, or 250 mg Tb/kg.
      The Tb distribution in organs was determined after 18-20 h of injection by using
      a spectrofluorometer. The concentrations of Ca, Mg, Fe, and Zn in various organs
      were determined by atomic absorption spectrometer. Tb administered was mainly
      found in pancreas, seminal vesicles, spleen, liver, and testes. In each organ. Tb
      concentration increased according to the dosage of Tb. Contrary to our
      expectation, the increase of Ca concentration was obvious in organs in which high
      Tb concentrations were found. The correlation coefficients between Tb and Ca
      concentrations were from 0.863 in spleen to 0.986 in liver. In heart, lung, and
      blood. Tb was scarcely detected and insignificant change of Ca concentrations was
      observed. This result suggests that Tb induces increased Ca concentrations in
      organs.

PMID- 1996469
TI  - Protective effect of zinc in the hepatotoxicity of bromobenzene and
      acetaminophen.
AB  - Mice of the Balb'c strain were administered bromobenzene (BB) or acetaminophen
      (AA) i.p., in single doses of 400 and 300 mg/kg, respectively. In the blood
      activity of SGOT and SGPT as well as SDH was determined. In the liver the level
      of metallothionein (MT), malondialdehyde (MDA) and glutathione (GSH) was
      measured. The level of MT as well as GSH (determined as non-protein SH groups)
      showed a significant increase following administration of zinc alone. Joint
      action of zinc and either BB or AA resulted in a decrease of GSH which was less
      pronounced than expected for each of the xenobiotics alone. The protective effect
      of zinc reflected in the reduction of the increase of SGPT and SGOT activity was
      apparent shortly (4 h) after administration of AA. A day after injection of AA
      alone the activity of enzymes was lower and the rate of decline followed the
      sequence SGPT greater than SGOT greater than SDH. For BB, both the toxic effect
      and the protective influence of zinc were apparent 24 h following administration.
      At 4 h in a group receiving BB alone no changes of the indicatory enzymes in
      blood were noted.

PMID- 1996471
TI  - Anesthesia alternatives for ophthalmic surgery.
AB  - 1. Traditionally, local anesthesia has only been used in patients with coexisting
      diseases that jeopardize the safety of general anesthesia. Local anesthesia,
      however, provides a number of advantages that make it suitable for ophthalmic
      surgery of both the anterior and posterior segment. 2. Preoperative emotional and
      physical assessment and patient counseling is essential to the successful use of
      local anesthesia. 3. Anxiety that exists intraoperatively can be relieved by
      sedentary social diversions such as listening to music, handholding, and other
      holistic approaches. 4. Discomfort caused by draping can be eliminated by using a
      drapeholder that lifts the drapes away, providing the patient with a high flow of
      air.

PMID- 1996472
TI  - AIDS and its effect on ophthalmology.
AB  - 1. Ocular manifestations of AIDS are, for the most part, due to the opportunistic
      infections and neoplasias seen in the syndrome. 2. Ocular manifestations seen in
      AIDS patients include cytomegalovirus, Toxoplasma gondii, Candida sp,
      Cryptococcus sp, herpes simplex or zoste, Mycobacterium sp, and ocular syphilis.
      3. Handwashing and disinfection of instruments are recommended to prevent
      transmission of infection in the ophthalmic practice.

PMID- 1996473
TI  - The choice of surgical procedure in congenital, infantile, and juvenile glaucoma.
AB  - 1. Trabeculotomy is successful in patients with an angle anomaly involving only
      the trabecular meshwork, but in those involving the trabecular meshwork with iris
      or cornea, trabeculotomy combined with trabeculectomy is recommended. 2. In cases
      of failed trabeculotomy or trabeculectomy, a Molteno implant can be tried,
      although it does not work well in patients with congenital glaucoma. 3. If all
      else fails, a cyclodestructive procedure is indicated and contact Nd:YAG laser
      cyclophotocoagulation is recommended.

PMID- 1996474
TI  - Nursing glasnost: treating burn victims in the Soviet Union.

PMID- 1996475
TI  - Manipulators don't last in the operating room.
AB  - Certain characteristics of the operating room are not conductive to successful
      manipulation. Given these characteristics, individuals who relate to others in a
      manipulative style are less likely to be found the operating room, but instead
      will choose a setting where there is more opportunity to meet needs in a
      manipulative manner. Nevertheless, it is important for the manager to be aware of
      manipulative behavior and to respond appropriately when it does occur. A manager
      who can handle manipulation can ensure that manipulators do not last long in the
      operating room.

PMID- 1996476
TI  - New paradigms for the '90s.

PMID- 1996477
TI  - Alcoholism-AIDS link studied.

PMID- 1996478
TI  - Future focus of AIDS.

PMID- 1996479
TI  - Relationship of transfusion and infectious complications after gastric carcinoma
      operations.
AB  - To determine the effect of transfusion on the incidence of postoperative
      infection, a retrospective cohort study of 196 patients who underwent surgery for
      gastric carcinoma in the period from 1985 through 1989 was carried out. Seventy
      one patients (36.2%) developed postoperative septic complications; they had
      received an average of 4.2 blood units, as compared with 2.7 units received by
      patients not affected (p less than 0.0053). The hypothesis of dose-response
      relationship is supported by the Mantel-Haenszel test, as applied to the overall
      results (p less than 0.01) and the results grouped by duration of operation (p
      less than 0.02). Furthermore, logistic regression analysis shows transfusion to
      be an independent risk factor in the incidence of infection (p less than 0.01),
      as are antibiotic prophylaxis (p less than 0.015), urinary tract catheterization
      (p less than 0.002), and the duration of surgery (p less than 0.027). This
      significance is attained after adjustment for age, gender, period of evolution of
      symptoms; preoperative infection(s), number of white cells, hemoglobin level and
      total proteins on diagnosis, location of tumor, tumor, nodes, and metastasis
      staging, operative technique, drainage of the area of operation, enteral
      nutrition, and the histologic studies and macroscopic appearance of the tumor.
      This study is further evidence that transfusion may cause an increased incidence
      of postoperative infection.

PMID- 1996480
TI  - Return of autologous blood donors as homologous blood donors.
AB  - Autologous blood donors (ABDs) have been reported to have favorable attitudes
      toward returning as homologous blood donors (HBDs), but the frequency of return
      has not been well documented. ABDs eligible by history to be HBDs were followed
      at one blood center: 255 donating for elective surgery and 234 donating during
      pregnancy were followed for an average of 18 months and 20 months, respectively,
      from time of eligibility after surgery or postpartum. Male ABDs had a higher rate
      of return as HBDs, as 34 percent (21/62) returned to donate an average of 3
      units, whereas 13 percent (56/427) of female ABDs returned as HBDs to donate an
      average of 2 units. Although a history of donation was associated with a higher
      rate of return (30%, 34/113), 11 percent (43/376) of ABDs with no history as HBDs
      returned to donate homologous units, despite having been recruited less
      frequently than prior HBDs. Overall, all male ABDs and female ABDs with an HBD
      history returned most frequently. The extra effort required for an autologous
      donor program may result in the recruitment of new donors into the HBD pool.

PMID- 1996481
TI  - Selective in vivo removal of rheumatoid factor by an extracorporeal treatment
      device in rheumatoid arthritis patients.
AB  - A prospective phase II trial was conducted to assess the feasibility, tolerance,
      and efficacy of a device designed for selective removal of rheumatoid factor from
      the plasma of rheumatoid arthritis patients. The device contained terpolymer
      hydrogel-coated plates with chemically attached, aggregated human immunoglobulin
      G, and it operated as an immunoaffinity column. Sixty-one patients aged 25 to 73
      underwent weekly plasmapheresis treatments (the primary therapy phase). During
      the trial, patients continued current rheumatoid arthritis medications without
      dose adjustments. All patients received two to six treatments (primary therapy).
      Responding patients were eligible to continue apheresis treatment every 2 to 6
      weeks (maintenance therapy). No serious, untoward side effects were noted in the
      course of this study; of 640 treatments, only 2 (in different patients) were
      aborted, one because of complaints of dizziness and angioedema and the other
      because of chest tightness and shortness of breath. Except for a significant (p
      less than 0.05) decrease in serum iron, no significant changes in complete blood
      count, serum electrolytes, renal and hepatic function tests, or serum C3 and C4
      were noted. Although the trial was not designed to determine clinical efficacy,
      patients noted less morning stiffness, longer time to onset of fatigue, and
      improved global pain assessment (p less than 0.004); significant objective
      improvements were noted in joint pain, tenderness, swelling, and the number of
      affected joints (p less than 0.001). One-half of the treated patients had at
      least a 50 percent improvement in objective measures of antirheumatic
      activity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1996482
TI  - Methods for measuring a 6 log10 white cell depletion in red cells.
AB  - Methodology is presented for enumerating very low concentrations of white cells
      (WBCs) in red cells (RBCs) by two separate measurement techniques. Both
      techniques rely on the method of harvesting WBCs from a 300- to 350-mL unit of
      RBCs and concentrating them to a volume of approximately 0.5 to 1.0 mL, which is
      equivalent to a WBC concentration of approximately 550 to 1. The WBC separation
      and concentration steps require less than 3 hours to complete, and multiple RBC
      units can be processed in parallel. Cell counting is carried out in a
      fluorescence hemocytometer or by a modified cytospin technique. As few as 1000
      WBCs in a unit of RBCs, which corresponds to a more than 6 log10 WBC depletion,
      can be measured without reaching the sensitivity limit of either technique (800
      and 200 WBC/unit, respectively). The harvesting method and counting techniques
      are relatively simple and inexpensive.

PMID- 1996483
TI  - A rare-event analysis model for quantifying white cells in white cell-depleted
      blood.
AB  - An analysis model to detect and quantify white cells (WBCs) in red cell
      concentrates (RBCC) drawn from units of blood that are highly depleted of WBCs is
      described. WBC detection is performed by fluorescence analysis of 50 microL of
      RBCC labeled with propidium iodide, a DNA/RNA fluorophore. Quantification is
      performed by regression analysis of standard dilutions of RBCC in substantially
      WBC-free red cells. This RBCC diluent is obtained by filtration of blood through
      a new medium. The method proves to be precise (CV = 7%), efficient (+/- 30
      min/aliquot), and linear (r = 0.99) to 6 log10 WBC depletion of the native
      product. The current technique is preferable to those suggested previously, such
      as ficoll concentration, which requires the sacrifice of the unit of blood for
      counting purposes, and to earlier fluorescence analysis techniques that do not
      employ WBC-free red cell diluents. The latter do not monitor extremely low
      concentrations of WBCs because they lack adequate signal-to-noise discrimination.
      The sensitivity of the described method allows for monitoring of WBC depletion
      procedures with greater efficiency than is currently available commercially.

PMID- 1996484
TI  - Cryopreserved platelets have decreased adhesive capacity.
AB  - The technique of freezing blood platelets has proven very useful in transfusion
      support of some patients who have become alloimmunized by prior transfusions.
      Although transfused frozen platelets have an acceptable life span in vivo,
      functional defects have been found when these cells were tested in vitro. The
      adhesive properties of frozen platelets were investigated by use of a modified
      Baumgartner chamber to perform paired perfusion studies of fresh versus frozen
      platelets or fresh versus 5-day-stored platelets from the same whole blood unit.
      Platelets were either frozen in liquid nitrogen with dimethyl sulfoxide as the
      cryopreservative or stored under standard blood bank conditions for 5 days. The
      freeze-thaw recovery of platelets was 73 +/- 8 percent. Frozen platelets
      exhibited a significant decrease in platelet adhesion as compared to fresh
      platelets from the same unit; adhesion of frozen platelets was only 53 percent of
      that of fresh platelets (p = 0.04). A slight, but insignificant decrease was
      noted with platelets stored for 5 days (86%, p = 0.197). These findings indicate
      that frozen-thawed platelets have a significant defect in adhesive capacity as
      compared to fresh platelets, and that platelets stored under blood bank
      conditions for 5 days maintain adhesive capacity well.

PMID- 1996485
TI  - Lack of increased bleeding after paracentesis and thoracentesis in patients with
      mild coagulation abnormalities.
AB  - To determine whether untreated mild coagulopathy in patients with no evidence of
      clinical bleeding is associated with an increased risk of hemorrhage after
      paracentesis or thoracentesis, retrospective examination was conducted of 608
      consecutive procedures for which prothrombin time (PT), partial thromboplastin
      time (PTT), platelet (Plt) counts, and preprocedure and postprocedure hemoglobin
      concentrations were available. There was no increased bleeding in patients with
      mild to moderate coagulopathy (defined as PT or PTT up to twice the midpoint
      normal range or pit count of 50 to 99 x 10(3) per microL [50-99 x 10(9)/L]).
      However, patients with markedly elevated serum creatinine levels (6.0 to 14.0
      mg/dL [530-1240 mumol/L]) had a significantly greater average hemoglobin loss (
      0.82 +/- 1.3 g/dL [-8 +/- 13 g/L], n = 11) than patients with normal serum
      creatinine levels (-0.12 +/- 0.88 g/dL [-1 +/- 9 g/L], n = 450) (p = 0.011).
      Overall, the frequency of bleeding complications requiring red cell transfusions
      was very low: 0.2 percent of events. The most common diagnosis for patients who
      had paracentesis was alcoholic liver disease (72%); for those having
      thoracentesis, it was infection (37%). It can be concluded that, for these
      patients, prophylactic plasma or platelet transfusions are not necessary.
      Patients with markedly elevated serum creatinine deserve close postprocedure
      observation.

PMID- 1996486
TI  - Hemolytic transfusion reaction following transfusion of frozen and washed
      autologous red cells.
AB  - A case of hemolytic transfusion reaction, accompanied by hypotension and followed
      by transient renal failure, occurred after the transfusion of 1 unit of
      previously frozen autologous red cells. Subsequent investigation revealed the
      probable cause of the hemolysis to be inadequate deglycerolization of the unit.
      The cause of the associated symptoms is unknown. Possibilities include
      nephrotoxic effects of hemoglobin or stroma, toxic effects of glycerol, or
      release of vasoactive or thrombogenic substances from lysed red cells. This case
      of a hemolytic reaction adds to the known risks of autologous transfusion.

PMID- 1996487
TI  - Fetomaternal hemorrhage: more data.

PMID- 1996488
TI  - Relapse of posttransfusion purpura after transfusion with frozen-thawed red
      cells.

PMID- 1996489
TI  - Two cases of paroxysmal cold hemoglobinuria with a Donath-Landsteiner antibody
      reactive by the indirect antiglobulin test using anti-IgG.

PMID- 1996490
TI  - Transfusion of bone marrow red cells during bone marrow harvests.

PMID- 1996491
TI  - The development of selective plasmapheresis as a means for specific therapeutic
      intervention.

PMID- 1996492
TI  - Preoperative autologous donation: what have we learned?

PMID- 1996493
TI  - [Arterial reconstruction in the lower extremities].

PMID- 1996494
TI  - [Infrainguinal bypass surgery of occlusive arteriosclerosis of the lower
      extremities using polytetrafluoroethylene (PTFE) vascular prostheses].
AB  - During the past 15 years, PTFE vascular prostheses have been employed as an
      alternative graft material in patients with peripheral arteriosclerosis of the
      lower extremity and no suitable autogenous saphenous vein for employment as a
      bypass route. PTFE is a porous polymer of teflon which becomes incorporated into
      the tissue by invasion of fibroblasts into the material after implantation. The
      result of the operation as indicated by the patency of the prosthesis depends on
      the length of the bypassed occluded arterial segment, the quality of the artery
      where the distal anastomosis is made, the preoperative fall in pressure in the
      extremity, coagulopathy and the development of intimal hyperplasia. The results
      after short bypass operations are insignificantly different from the results
      after the use of autologous saphenous vein. The use of PTFE in infrainguinal
      bypass operations is an acceptable alternative to autogenous saphenous vein.

PMID- 1996495
TI  - [Optimizing warfarin treatment].
AB  - For monitoring of warfarin treatment only analyses with documented International
      Sensitivity Index should be used. Until further studies clarify the matter, we
      recommend the therapeutic intervals proposed by the American College of Chest
      Physicians and the National Heart, Lung, and Blood Institute. For induction of
      treatment, a daily warfarin dose of 10 mg is useful. Overlapping heparin therapy
      is recommended for at least five days. Day-to-day variation of dietary vitamin K
      intake of less than 250-500 micrograms and an alcohol consumption below 47 g/day
      will not disturb anticoagulation. Bleeding is more common during long-term
      treatment, among elderly patients and in patients with cerebral arteriosclerotic
      disease, especially in combination with uncontrolled hypertension. Bleeding
      patients often have underlying pathology which should be looked for.

PMID- 1996496
TI  - [Transesophageal echocardiography. A new cardiologic examination method].
AB  - Transoesophageal echocardiography is a new diagnostic method which uses the
      oesophagus as an ultrasonic window to the heart and central vessels. The images
      obtained are often of supreme quality compared to those obtained by conventional
      transthoracic echocardiography, because the distance between the transducer and
      the heart is reduced. The equipment, the examination technique, and preliminary
      experience after 80 examinations are described. It is concluded that the
      technique is particularly informative in patients with endocarditis or mitral
      valve disease and that the transoesophageal approach has become essential for the
      diagnosis of prosthetic valve dysfunction. Furthermore, the technique allows
      visualization of the descending aorta, which is often impossible to image from
      the precordial window, and the technique has proved useful in the emergency
      diagnostic elucidation of aneurysm of the thoracic aorta. So far a limited number
      of formal investigations comparing the results of transoesophageal
      echocardiography with the results of reference methods have been performed,
      however, practical clinical experience is already sufficiently extensive to state
      that transoesophageal echocardiography has come to stay. Disregarding coronary
      angiography it seems probable that combined transthoracic and transoesophageal
      echocardiography with time will eliminate the need for cardiac catheterization
      and angiography.

PMID- 1996497
TI  - [Street violence in Arhus].
AB  - As part of a one-year prospective investigation of all violent accidents in Arhus
      undertaken in the casualty departments and the Medicolegal Institute, the extent
      and severity of street violence were analysed and compared with violence in and
      near pubs. Street violence constituted 26% of all accidents due to violence and
      involved 1.3 persons per day. 75% were blameless and 68% of these were attacked
      outside the region where they lived. Violence in the street, in pubs and in the
      vicinity of pubs was concentrated in the centre of the city, in the evening and
      night hours, at weekends and involved young men. Street violence and violence in
      the vicinity of pubs differed from violence in pubs in that significantly more of
      the victims were blameless (approximately 75%), several persons were the
      perpetrators (approximately 40%) and blows and kicks were combined (approximately
      15%). As assessed by the Abbreviated Injury Scale (AIS), the lesions sustained in
      street injury did not differ from those of violence in or near pubs: 86% were
      minor injuries, 11% moderate and none proved fatal. 75% of the victims could be
      treated completely in the casualty department or by the general practitioner or
      dentist. Street violence is concentrated to the middle of the city, at weekends
      and in the evening and night hours and is similar in many ways to violence in and
      near pubs. The authors consider that exposure to street violence is, to a great
      extent, connected with participation in night life of the city.

PMID- 1996498
TI  - [Violence and women in Arhus. Changes in the 1980's].
AB  - As part of a one-year prospective investigation of accidents due to violence in
      Arhus carried out by the casualty departments and the Institute of Forensic
      Medicine in cooperation with the Arhus Police and the Crisis centre for female
      victims of violence, the fraction of violence which involved women was analysed.
      A total of 492 contacts were received from 424 women. The average age was 32
      years. The home was the commonest site of violence with the husband as the
      commonest perpetrator of violence (192). In 98 cases the perpetrator was unknown.
      The majority had received blunt injuries (blows and/or kicks). The lesions
      frequently appeared to be limited from a therapeutic viewpoint. In 143 women,
      however, the lesions were potentially serious. Thirteen women were hospitalized
      and 60 were referred for treatment in other departments. Violence was commonest
      in the evening and night hours and there was a tendency to an increase towards
      the end of the week. The majority (279) stated that the episode was not their
      fault. The police were contacted in 25% of the cases. A total of 164 requests
      were made for access to the Crisis Centre by female victims of violence. Of
      these, 30 women had been seen by a doctor and 23 had previously been
      hospitalized. Compared with conditions five years previously, a considerable
      increase in the number of registered violent accidents to women was observed. On
      the other hand, no definite evidence was found that the nature of the violence to
      which they had been exposed had altered during the past five years.

PMID- 1996499
TI  - [Choice of contraception in relation to sexual activity among younger women in
      Nuuk/Godthab (Gronland) and in Nykobing Falster (Danmark). A population-based
      cross-sectional study among 1,247 women].
AB  - Contraceptive habits in relation to sexual activity were investigated in a
      population-based cross-sectional investigation. A total of 661 women from
      Nykobing Falster and 586 women from Nuuk/Godthab in Greenland participated. The
      women, who were in the age group 20-39 years, were selected at random from the
      census and all underwent a personal interview. Both in Godthab and in Nykobing
      Falster a "non-barrier" method of contraception was the commonest method
      employed, regardless of the number of sexual partners. In Godthab, the majority
      had thus employed IUDs and in Nykobing Falster, oral contraception was the method
      most employed. In Godthab, 9-22% had employed condoms on one or other occasion
      and the prevalence of this was found to increase with the number of sexual
      contacts. In Nykobing Falster 57-63% had employed condoms but no significant
      variation was observed between various categories of numbers of partners in this
      area. From the point of view of prevention of sexually transmitted disease, it is
      striking that among women with greater than or equal to 20 sexual partners,
      approximately 79% and approximately 40% in Godthab and Nykobing Falster,
      respectively, had never employed condoms or diaphragms. In future, it will be
      important to investigate the patterns of sexual behaviour in various cultures and
      their development during the course of time in order to advise a population on
      the basis of the norms found in the culture concerned.

PMID- 1996500
TI  - [Prevention of athletic injuries by changing the regulations. Experiences with a
      military obstacle track].
AB  - During a period of 12 months of military conscription, all of the injuries
      occurring on the obstacle track at the Antvorskov Barracks in Slagelse were
      registered. During the period of investigation, the regulations for employing the
      track were altered so that the heights of jumping down from obstacles were
      considerably reduced. The object of this investigation was to demonstrate any
      possible effect on the pattern of injuries. During the period, a total of 26
      injuries were registered (3.78 injuries/conscript/1,000 hours activity). As
      compared with previous investigations, the frequency of injuries was reduced and
      practically all of the serious injuries were prevented. The proposed alterations
      in the techniques are recommended in future when conscripts employ the military
      obstacle track.

PMID- 1996501
TI  - [The attitude of pregnant women to ultrasound screening. A questionnaire study].
AB  - Ultrasound screening of pregnant women is recommended by the Danish National
      Health Organisation only when the investigation is indicated, and not as part of
      routine antenatal care. The press has suggested that ultrasound examination makes
      pregnant women feel anxious and insecure. The attitude of the pregnant women to
      ultrasound screening is illustrated by a questionnaire investigation, including
      220 women. Most of the women (93%) thought, that ultrasound examination should be
      offered to all pregnant women, while only 4.3% thought, that ultrasound screening
      should be offered only on special indications. Most of the women thought, that
      ultrasound examination was a positive experience, enhancing the women's feeling
      of security.

PMID- 1996502
TI  - [Neonatal conjunctivitis after the abolition of compulsory Crede prophylaxis].
AB  - The prescript requiring application of silver nitrate eye drops (0.66% AgNO3) to
      the conjunctivae of the newborn within two hours after delivery was revoked in
      March 1985. The present study comprises a prospective investigation of the
      occurrence of microorganisms in specimens of eye secretion from neonates received
      during the period February-April 1986, and a review of findings of Neisseria
      species and B. catarrhalis in 3,485 specimens of ocular secretions and of C.
      trachomatis in 1,240 conjunctival scrapes received at the Neisseria Department
      1986-1988. The numbers of cases of conjunctivitis neonatalis caused by the
      following microorganisms were: N. gonorrhoeae 8, N. cinerea 6, other Neisseria
      species 8, B. catarrhalis 49 and C. trachomatis 92. During the period 1984-1988,
      the total number of neonates with gonococcal conjunctivitis neonatalis was 18.
      The gonococcal infection was diagnosed within the first week of life in 50% of
      the cases but could occur as late as in the fourth week of life. Similarly,
      infection with B. catarrhalis was most common in neonates less than one week old
      (49%), whereas chlamydial infection was most common in the second week of life
      (39%). It is concluded that the eyes of neonates should be carefully observed for
      at least four weeks and that microbiological examinations for gonococci and
      chlamydia are indicated if signs of infection appear.

PMID- 1996503
TI  - [Renal involvement during intravenous treatment with acyclovir].
AB  - A woman aged 70 years developed reversible renal involvement during intravenous
      treatment with acyclovir. In order to prevent renal involvement during treatment
      with acyclovir, the following precautions are recommended: acyclovir should be
      infused slowly, regular control of renal function should be undertaken and the
      dosage should be reduced if evidence of renal involvement is found.

PMID- 1996504
TI  - [Rectal ameboma].
AB  - After a stay in the far east, a man aged 20 years developed difficulty in
      defaecation and slight difficulty in micturition. Rectoscopy revealed a stenosing
      tumour resembling a carcinoma. The tumour disappeared completely following
      treatment with amoebicides. Surgical treatment of amoebomata is associated with
      complications and is warned against.

PMID- 1996505
TI  - [Chorionic villi biopsy].

PMID- 1996506
TI  - Should you co-sign someone else's charting?

PMID- 1996507
TI  - Global budgeting.

PMID- 1996508
TI  - Teaching lower gastrointestinal endoscopy: a comparison of family medicine and
      internal medicine residencies.
AB  - Lower gastrointestinal endoscopy (LGIE) is an important procedure in primary care
      for detecting colorectal cancer. This survey of family practice (FP) and internal
      medicine (IM) residency directors in the southeastern United States shows that
      100 percent of FP and 92 percent of IM programs provide training in LGIE. Less
      than half of all programs had certification criteria, and both disciplines showed
      a clear preference for the 60-cm flexible sigmoidoscope. LGIE procedures in IM
      programs were more frequently supervised by gastroenterologists, and in FP
      programs they were more frequently supervised by FP faculty. Only 55 percent of
      FP and 56 percent of IM residents were predicted to suggest screening LGIE to
      their patients, and 80 percent of FP and 63 percent of IM residents were
      predicted to include sigmoidoscopy in the evaluation of hematochezia.

PMID- 1996509
TI  - Rural patients' interests in preventive medical care.
AB  - A number of national studies have reported patients' interests in preventive
      medical care, but rural populations have not been well studied. We surveyed
      patients from a major clinic in rural central Minnesota to determine their
      interests in preventive medical care and their physicians' perceptions of those
      interests. Of 270 patients who responded to a questionnaire, 63-93 percent agreed
      that physicians should perform a wide variety of primary and secondary preventive
      medical services, such as periodic health examinations and counseling about
      smoking, exercise, and diet. Study physicians recommended most preventive medical
      services at least as often as did their patients, but physicians consistently
      underestimated patients' wishes for these services. Our results indicate that
      this rural clinic population is interested in a broad range of preventive medical
      services, which was not fully appreciated by the physicians.

PMID- 1996510
TI  - The effect of microcomputer-generated reminders on influenza vaccination rates in
      a university-based family practice center.
AB  - Less than 20 percent of elderly and other high-risk persons targeted for annual
      influenza vaccination are immunized each year. In most busy practice settings, it
      is difficult for primary care physicians to identify every patient in need of
      preventive health interventions. The purpose of this study was to assess the
      effect of microcomputer-generated reminders on influenza vaccination rates in a
      university-based family practice center. The practice uses an interactive
      encounter form system from which updated clinical information is routinely
      entered into a cumulative database. During a 2-month period, 686 patients were
      identified in the database as eligible to receive influenza vaccine according to
      accepted criteria. Practice physicians (n = 32) were stratified by level of
      training and randomized to one of three groups, thereby receiving printed
      reminders on the encounter forms of all, none, or half of their eligible
      patients. Patients of physicians who always received reminders were more likely
      to receive influenza vaccine during the study period than patients of the never
      reminded physicians (51 percent versus 30 percent, P less than 0.001). Patients
      whose physicians received reminders for only half their patients had an
      intermediate likelihood of receiving a vaccination if a reminder was printed (38
      percent) but were less likely than the patients of never-reminded physicians to
      receive the vaccine if no reminder was printed (20 percent, P less than 0.001).
      This study suggests that physicians learn to depend on reminders for preventive
      health activities and that reminders are most effective when they are provided at
      every patient encounter.

PMID- 1996511
TI  - Reorganizing a family practice center: strategy to save a residency program at a
      financially troubled hospital.
AB  - The family health center of a family practice training program was eliminated
      from the county hospital budget following funding cuts, forcing the program
      faculty to create an independent nonprofit community clinic in which to train
      residents and provide care to established patients. A county audit of the new
      clinic after 2 years' operation showed substantial savings, particularly for
      administrative overhead. This report presents data showing the cost advantages to
      a small private clinic with faculty management compared with costs in a hospital
      managed outpatient clinic; the savings were sufficient to assure continuation of
      the training program. Increased flexibility under faculty management provided a
      more realistic teaching environment and new research opportunities.

PMID- 1996512
TI  - Anxiety and substance use disorders: a primer for primary care physicians.
AB  - Primary care physicians encounter many patients with primary and secondary
      anxiety and substance use problems. Some patients have a dual diagnosis of both
      an anxiety and a substance use disorder. Symptoms may be overdiagnosed,
      underdiagnosed, and misdiagnosed. This article provides the primary care
      physician with an overview of the relation between psychoactive substance use
      disorders and anxiety symptoms. Also described are drug use patterns and
      diagnostic criteria for psychoactive substance use disorders. A model for
      understanding the role of anxiety symptoms during drug use is provided.

PMID- 1996513
TI  - Collagenous colitis as a cause of chronic diarrhea.
AB  - When the usual workup for chronic diarrhea fails to provide a diagnosis and the
      endoscopic findings are normal, alternative etiologies must be considered. This
      case of collagenous colitis represents such an alternative diagnosis. The patient
      is a 65-year-old woman who complained of abdominal cramps and watery diarrhea for
      an 8-month span. The key element to her diagnosis was subepithelial collagen
      deposits of the mucosa of the colon. Her symptoms were resolved with supportive
      care, diet, and diphenoxylate. Essential features and treatment of collagenous
      colitis are reviewed.

PMID- 1996514
TI  - Current report--HIV. Recommendations for treatment of acute Pneumocystis carinii
      pneumonia.

PMID- 1996515
TI  - Blood cholesterol lowering in elderly patients.

PMID- 1996516
TI  - Dorsal penile nerve block.

PMID- 1996517
TI  - Infectious vaginitis.

PMID- 1996518
TI  - Epidemiological abuse.

PMID- 1996520
TI  - Current options in the management of rectal cancer.

PMID- 1996519
TI  - Hypocholesterolemia in childhood.

PMID- 1996521
TI  - Thrombolytic therapy.

PMID- 1996522
TI  - The current management of cutaneous melanoma.
AB  - Theoretically ELND may be beneficial for the subset of patients who are likely to
      have occult metastases at the time of diagnosis. The natural history of melanoma,
      well described from large data bases, has identified a group of patients with
      "intermediate-thickness" melanomas as the potential beneficiaries. However,
      pathologic specimens obtained from ELND have demonstrated a much lower incidence
      of occult disease (15%) than what would be anticipated based on the estimated
      risk of developing clinically detectable metastasis, more than 50%. Possible
      explanations for this discrepancy are as follows: (1) routine pathologic
      examination fails to detect micrometastases accurately thus, grossly
      underestimating the true incidence of occult disease and/or (2) patients who are
      at high risk for metastases have not yet developed regional disease at the time
      of diagnosis and performance of the ELND. In the latter situation, ELND would
      provide expectant palliation by preventing regional node relapse but would not be
      expected to impact on survival. Clearly, however, at least three retrospective
      studies have demonstrated a survival benefit when using ELND for the treatment of
      patients in the subgroup with intermediate-thickness melanomas. Prospective
      studies have not confirmed these same results, but they have not targeted the
      study to the same group of patients. In order to resolve the differences, we have
      initiated a prospective randomized multi-institutional surgical trial to
      ascertain the efficacy of ELND in patients with tumor thickness between 1 and 4
      mm. More than 700 patients have been entered on this study. Results should
      provide valuable insights as to the true incidence of occult regional disease and
      determine if the removal of this disease translates into a survival benefit. In
      the meantime, the practice of ELND should be a selective one. The decision should
      be individualized in an attempt to maximize the potential benefit and minimize
      the morbidity. Tumor thickness, presence or absence of ulceration, anatomical
      site of primary, and sex of the patient are all important criteria for estimating
      the risk of metastasis. The elderly and obese are more likely to suffer from long
      term complications of lymphadenectomy, and therefore the risk and benefits must
      be meticulously evaluated before application of ELND in this patient population
      is undertaken.

PMID- 1996523
TI  - The evaluation of blunt abdominal trauma: computed tomography scan, lavage, or
      sonography?

PMID- 1996524
TI  - The management of coagulation problems in the surgical patient.

PMID- 1996525
TI  - The current management of gastroesophageal reflux.

PMID- 1996526
TI  - Surgery in the aged.
AB  - Coincident with improvement in medical care and life-styles, the longevity of the
      population of the United States is increasing. As the population ages, more
      surgical procedures will be performed in elderly patients. The effects of the
      aging process on organ systems generally does not compromise function under
      normal conditions. However, the elderly patient may not be able to meet the
      metabolic demands of a hypermetabolic state. Operative outcome for the most part
      is related more to the urgency of the procedure than to the age of the patient.
      With the proper preoperative evaluation and postoperative care, the elderly
      patient at risk for perioperative morbidity and mortality can be identified and
      outcome approved. In most cases age in and of itself is not a contraindication to
      surgical intervention. Surgical problems in the aged patient can and should be
      safely managed with early elective management prior to the development of
      emergent situations.

PMID- 1996527
TI  - Soft tissue sarcomas of the extremity and retroperitoneum: advances in
      management.
AB  - The treatment of soft tissue sarcomas continues to pose significant challenges.
      The past decade has seen a dramatic increase in multimodality therapy for these
      tumors, with a resultant decrease in the number of amputations performed for
      extremity lesions. Even with combined modality treatment, however, the prognosis
      remains grim for most patients with retroperitoneal sarcomas, in which delay in
      diagnosis and tumor proximity to vital structures hinder the chances for cure.
      Improved protocols for the treatment of retroperitoneal sarcomas must be
      developed if we are to match the successes achieved with extremity tumors. As
      efforts to decrease local recurrence of extremity sarcomas have been largely
      successful, a new challenge to decrease the frequency of systemic metastases has
      emerged. Although aggressive surgical approaches to recurrent and metastatic
      sarcomas can result in long-term survival in some cases, better treatments are
      needed for those patients whose resections fail or those who are not candidates
      for resection. Combined modality treatments and new modalities, such as adoptive
      immunotherapy, need to be carefully evaluated in this group of patients. Enormous
      strides have been made in the treatment of osteogenic sarcomas and some pediatric
      soft tissue sarcomas. Additional research into basic tumor biology, as well as
      major intergroup studies of therapy, will be necessary if we are to duplicate
      those achievements in the more refractory adult soft tissue sarcomas.

PMID- 1996528
TI  - Current management of pancreatic abscess.
AB  - Without surgical debridement in patients with infected pancreatic necrosis,
      survival can not be expected. Previous surgical series reported postoperative
      survival in the range of 50%; however, more recent reports demonstrate improved
      mortality of 10% to 20%. Despite the demonstrated advances in surgical
      management, much remains to be done. Ongoing sepsis and the multiorgan failure
      syndrome (including ARDS, renal, and hepatic failure) are frequently part of the
      terminal phase of necrotizing pancreatitis, and further declines in mortality
      await future improvements in supportive therapy for overwhelming sepsis. Finding
      a means to prevent secondary infection of necrotizing pancreatitis would also
      have a very significant impact on survival. Defining the various form of severe
      acute pancreatitis and its infectious complications by dynamic pancreatography
      and CT-directed aspiration will permit meaningful trials of new methods to treat
      these unfortunate patients.

PMID- 1996529
TI  - Modern immunotherapy of cancer.

PMID- 1996530
TI  - An argument in favor of all-autogenous tissue for vascular bypasses below the
      inguinal ligament.

PMID- 1996531
TI  - An argument against all-autogenous tissue for vascular bypasses below the
      inguinal ligament.
AB  - 1. Femoropopliteal bypass, regardless of the conduit used, has a 5-year failure
      rate. 2. The majority of patients with initial reconstruction failure will
      require secondary repair. 3. Recognition of the ultimate need for secondary
      repair justifies a long range planning approach for the management of patients
      who require femoropopliteal reconstruction. 4. Secondary repairs have a
      dramatically higher patency rate when performed with autogenous saphenous vein
      than they do with PTFE grafts. 5. Patients who had the initial operation
      performed with PTFE will have autogenous saphenous vein available for secondary
      repair, in contrast to the patients who had saphenous vein used in the initial
      operation; they must rely upon second-best choices including amputation. 6. The
      greatest and longest term of effective palliation, relief from disabling
      claudication, or limb salvage will be achieved when PTFE is used preferentially
      for the first femoropopliteal reconstruction. In the majority of patients, this
      will be the only operation necessary; they will have had a simple operation,
      requiring a short period of time, and probably reduced hospitalization. For those
      who require secondary repair, autogenous saphenous vein is available for that
      purpose and will yield the best long-term results in comparison to the other
      alternatives including amputation. Thus, the concept of staged infrainguinal
      repair using first PTFE and, if necessary, saphenous vein for the secondary
      repairs provides the longest term palliation for patients with lower extremity
      arterial occlusive disease.

PMID- 1996532
TI  - Cardiovascular risk factors and the effects of intervention.
AB  - Cardiovascular risk factors can be substantially modified by changes in life
      style such as diet, exercise, smoking cessation, and moderation of alcohol
      consumption. In turn, these can reduce blood pressure, heart rate at rest, and
      blood lipid concentrations. Epidemiologic evidence shows that for every 1% change
      in serum cholesterol levels, there is a 3% change in the likelihood of developing
      coronary heart disease. In addition, a long-term (5-year) change of 5 to 6 mm Hg
      in diastolic blood pressure can reduce the chances of stroke by 35 to 40% and of
      coronary heart disease by 20 to 25%. The full impact of this broad range of
      interventions on population health has still to be fully realized in many
      countries, including the United Kingdom, however it is likely to be considerable.
      Some of the recent evidence in support of such cardiovascular risk factor
      modification is selectively reviewed.

PMID- 1996533
TI  - Ambulatory blood pressure monitoring in the evaluation of drug efficacy.
AB  - Conventional clinic measurement of blood pressure is influenced by many factors
      that make the technique unsuitable for the assessment of antihypertensive drug
      efficacy. The major drawback of conventional measurement is that it cannot
      indicate the duration of drug effect or the influence of antihypertensive drugs
      on nocturnal blood pressure. Noninvasive 24-hour ambulatory blood pressure
      measurement has a number of advantages over conventional measurement: it provides
      a profile of blood pressure over the 24-hour period; it detects white coat
      responders; it is free of regression to the mean and the placebo response,
      thereby making it possible to consider efficacy studies which need not have a
      placebo phase; it enables considerably more observations than is possible with
      clinic measurement by increasing the power of studies, which may reduce
      significantly the numbers of patients needed for antihypertensive drug studies.
      Twenty-four-hour ambulatory blood pressure measurement offers the opportunity to
      study antihypertensive drugs in fewer patients with greater accuracy than is
      possible with conventional clinic measurement and should be a mandatory
      requirement for such studies.

PMID- 1996534
TI  - AIDS series--paper III-A. AIDS policy for the workplace: a case study of
      Baltimore City policy.

PMID- 1996535
TI  - AIDS series--paper III-B. Prevention of HIV transmission in the workplace:
      categorization of jobs and tasks by risk of HIV infection.
AB  - The risk to workers of exposure to HIV or other blood-borne infectious diseases
      on the job is dependent upon the likelihood of exposure to blood, body fluids, or
      tissues while performing the tasks required by the job. Three categories of
      workplace-associated risk of HIV exposure have been defined. These categories can
      be summarized as follows. Category I--Regular or Frequent Exposure Potential.
      Applies primarily to health-care workers, including emergency medical workers.
      These workers are at greatest risk of occupationally acquired HIV disease.
      Category II--Intermittent Exposure Potential. Applies to persons such as police
      officers, fire fighters, and correctional facility personnel. Category III--Rare
      or No Exposure Potential. Applies to most jobs in the service and manufacturing
      industries, including office personnel. These workers are at no greater risk than
      the general public for exposure to HIV. As there is definite risk to Category I
      and II workers of becoming infected with HIV while performing duties required by
      their jobs (their risk of acquiring HBV is much greater), it is important for
      employers in these workplaces to establish procedures to prevent the exposures
      that may lead to infections. The first step in this process is to analyze
      carefully tasks performed within the workplace to identify Category I and II
      tasks, as described in the DOL/DHHS Joint Advisory Notice. Once this has been
      done, the DOL/DHHS document and pertinent CDC recommendations should be used to
      develop specific procedures for those workers at risk.

PMID- 1996536
TI  - Design modifications of a class II biological safety cabinet and user guidelines
      for enhancing safety.
AB  - Class II Biological Safety Cabinets (BSCs) are widely used in biological and
      chemical research for protection of the investigator, the environment, and the
      project. However, researchers' operational procedures are often inconsistent with
      BSC design limitations. While the Class II BSC is only a partial containment
      cabinet, better design and user training can improve containment, thereby
      increasing personnel protection. The authors developed design modifications for a
      Class II BSC to permit internal waste collection and to optimize the available
      work area. An internal recessed well for the waste receptacle, relocation of
      petcocks and electrical duplex, and installation of a new vacuum bottle make
      operation of the cabinet more efficient and potentially safer. To correct poor
      work practices, which can compromise the protective features of any BSC, precise
      guidelines and training programs should be relied on. Standardization of
      guidelines for operation of BSCs would be beneficial to the clinical and research
      community, given the frequent exchange of investigators among biomedical
      institutions.

PMID- 1996537
TI  - Exposure variability in the workplace: its implications for the assessment of
      compliance.
AB  - Day-to-day variations of occupational exposures have important implications for
      the industrial hygienist trying to assess compliance with an occupational
      exposure limit. As only a limited number of samples are taken during an
      observation period, extrapolations are required to estimate exposures over the
      unsampled period. Compliance may be evaluated using estimates of the geometric
      mean (GM) and the geometric standard deviation (GSD) to calculate a confidence
      interval around the mean exposure and compare this interval to a limit value,
      assuming a lognormal distribution of exposures over time. These confidence
      intervals are very sensitive to the estimate of GSD. Hence, the questions of when
      to sample and how many samples to take for a reliable assessment of exposure
      variability (GSD) are the focus of this paper. Analyses of simulated exposure
      time series and 420 data sets of personal exposures with three or more
      measurements obtained from actual workplaces demonstrate that the small number of
      samples usually collected during surveys leads to biased estimates of the
      variance of the exposure distribution. There is a high likelihood of an
      underestimate of variance, which rapidly increases if 8-hr time-weighted average
      samples are collected on consecutive days or within a week. The results indicate
      that in 80% of the within-week exposure-time series, the estimated GSD may be too
      low, even up to a factor of 2. Evidence is presented that autocorrelation is a
      likely explanation for the bias observed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1996538
TI  - Abnormalities in serum enzymes in skeletal muscle diseases.

PMID- 1996539
TI  - Markers as prognostic indicators in medullary thyroid carcinoma.

PMID- 1996540
TI  - Medullary thyroid cancer. An immunohistochemical and humoral study using six
      separate antigens.
AB  - The authors investigated the humoral and tissue expression of six antigens
      associated with medullary thyroid cancer (MTC): calcitonin (CT), calcitonin gene
      related peptide (CGRP), carcinoembryonic antigen (CEA), neuron-specific enolase
      (NSE), somatostatin (SRIF), and thyroglobulin (TG). The antigens were studied in
      the neoplastic C cells using immunohistochemistry with specific antisera and in
      the plasma using specific radioimmunoassay. Eighteen patients (8 male and 10
      female patients, aged 12-72 years) were studied. Mean follow-up was 70.7 months
      (range, 2-179 months). Nine patients (50%) died of their disease after a mean
      follow-up of 47.2 months (range, 2-116 months). By immunostaining, primary tumors
      expressed CT and CEA in all cases and NSE was positive in 90%, CGRP in 66%, SRIF
      in 63%, and TG in 58%. Metastatic tissues were positive in all cases of CT
      staining, 92.8% of CEA, 71.4% of NSE, 73.3% of CGRP, 38.5% of SRIF, and only
      13.3% of TG staining. In positive cases the percentage of positive cells and the
      degree of staining were variable among the different antigens. The expression of
      an antigen in the neoplastic cells was associated with the hypersecretion of the
      corresponding antigen in the circulation in the case of CT and CEA. The levels of
      these antigens were elevated in all patients with metastases and could accurately
      predict the appearance of new metastases or indicate the effective treatment of
      previous metastases by surgery. In the case of NSE, CGRP, and SRIF, few patients
      had increased plasma concentrations of the antigens and these usually occurred
      during very advanced phases of the disease. Detectable levels of serum TG were
      never observed. When the outcome of the disease was compared with the expression
      of CT, CEA, NSE, CGRP, and TG, no correlation could be found. On the contrary,
      SRIF expression in the primary tumor could differentiate two groups of patients
      with different survival rates. SRIF-positive patients had survival rates of 100%
      and 50% at five and seven years, respectively, whereas SRIF-negative patients had
      survival rates of 40% at five years and 25% at seven years.

PMID- 1996541
TI  - Papillary carcinoma of thyroid with exuberant nodular fasciitis-like stroma.
      Report of three cases.
AB  - Three examples of an unusual morphologic variant of papillary thyroid carcinoma
      (PTC) are reported. The presence of a prominent stromal component resulted in low
      power microscopic appearances resembling fibroadenoma, phyllodes tumor, or
      fibrocystic disease of the breast in two cases. The carcinomatous component grew
      in the form of anastomosing narrow tubules, clustered glands, solid sheets with
      or without squamous differentiation, and/or papillae, and exhibited the typical
      nuclear features of PTC. The abundant stroma had a nodular fasciitis-like quality
      and was composed of short fascicles of spindle cells separated by varying amounts
      of mucoid matrix, collagen, and extravasated red blood cells; this was
      interpreted as an exuberant mesenchymal reaction to the carcinoma. The importance
      of recognizing this variant of PTC is that, when one encounters a
      fibroproliferative lesion of the thyroid, a diligent search should be made for
      papillary carcinoma. This variant also must be distinguished from the vastly more
      aggressive papillary carcinomas with anaplastic transformation and the so-called
      carcinosarcomas.

PMID- 1996542
TI  - Granulomatous prostatitis and poorly differentiated prostate carcinoma. Their
      distinction with the use of immunohistochemical methods.
AB  - Granulomatous prostatitis and poorly differentiated prostate carcinoma can mimic
      each other both clinically and histologically. To develop criteria useful in
      resolving problem cases, the authors compared the reactivities of these
      conditions (nine cases of granulomatous prostatitis and six cases of poorly
      differentiated carcinoma) with a panel of antibodies to cytokeratin (AE1/3),
      prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), lysozyme,
      antimacrophage M, and leukocyte common antigen (LCA). In granulomatous
      prostatitis, histiocytes were not immunoreactive for PAP, PSA, or cytokeratin;
      however, histiocytes reacted to lysozyme in nine of nine cases, antimacrophage M
      in seven of nine cases, and LCA in one of nine cases. Tumor cells from all six
      carcinoma cases reacted with PAP, PSA, and cytokeratin; all failed to react with
      lysozyme, LCA, and antimacrophage M. The authors conclude that granulomatous
      prostatitis and poorly differentiated carcinoma can be reliably distinguished
      with immunohistochemical methods.

PMID- 1996543
TI  - Ovarian myxoma. A study of two cases with long-term follow-up.
AB  - Two cases of the so-called ovarian myxoma are reported. One was from a 13-year
      old girl who had a 31-year follow-up and no evidence of recurrence. The second
      case, from a 65-year-old woman, recurred intraperitoneally, 19 years after the
      surgery. Both tumors were myxoid, with round to stellate cells.
      Immunohistochemical, electron microscopic (EM), and DNA flow cytometric (FCM)
      studies were performed on formalin-fixed, paraffin-embedded tissue of the second
      patient on both the primary tumor and the recurrence. Tumor cells expressed
      vimentin and were focally positive for desmin and myoglobin. EM findings
      suggested a fibroblastic differentiation. An aneuploid cell population was
      present in the recurrent tumor by DNA-FCM studies. Only four other cases of so
      called ovarian myxoma were reported to date, and the follow-up does not exceed 18
      months. The authors conclude that the presence of aneuploidy and the late
      recurrence of one of their cases suggest that certain ovarian myxomas might
      behave like low-grade sarcomas. The histogenesis of this tumor remains unsettled,
      but similarities were found with myxomas in other locations.

PMID- 1996544
TI  - Gene rearrangements in the diagnosis of lymphoma/leukemia. Guidelines for use
      based on a multiinstitutional study.
AB  - The demonstration of immunoglobulin or T-cell receptor gene rearrangements in
      human lymphoproliferative processes with the use of DNA hybridization has gained
      great popularity as a sensitive laboratory adjunct to diagnostic hematopathology.
      The fact that nearly all B- or T-cell malignant lymphomas and leukemias have one
      or more rearranged antigen receptor genes provides a biologic basis for a
      diagnostic test. To formally analyze the sensitivity, specificity, and
      reproducibility of gene rearrangements in the diagnosis of human
      lymphoproliferative disease, the authors conducted a large, multiinstitutional
      study. Through a blinded, controlled approach, gene rearrangement analysis of 275
      cases was shown to carry a high correlation with conventional phenotyping and
      histologic diagnosis, with only minor false-positive and false-negative rates.
      Significantly, no rearrangements were detected in normal lymphoid tissues or
      carcinomas, sarcomas, or melanomas. In a randomized study of 50 cases, laboratory
      results showed a high rate of interlaboratory agreement, regardless of the level
      of previous experience. Furthermore, the reproducibility of interpretation of
      data (Southern blot autoradiograms) of 192 cases showed high concordance among 11
      observers from multiple laboratories. Based on these findings, the authors
      propose a set of guidelines for interpretation of gene rearrangement analysis
      that, if carefully followed, renders this a highly reproducible, safe, and
      accurate addition to the diagnostic regimen for human lymphoproliferative
      processes.

PMID- 1996545
TI  - Bone marrow findings after treatment with recombinant human interleukin-3.
AB  - In a phase I/II study, bone marrow biopsy specimens and aspirates of 20 patients
      with malignant tumors but normal bone marrow (n = 6), bone marrow failure
      resulting from chemotherapy (n = 4), myelodysplastic syndrome (n = 5), and
      aplastic anemia (n = 5) were evaluated before and after patients were treated
      with recombinant human interleukin-3 (rhIL-3). This cytokine proved to be an
      effective hematopoietic growth factor with only mild side effects. The rhIL-3
      treatment led to increased overall bone marrow cellularity with trilinear
      stimulation of hematopoietic cells, except in most patients with aplastic anemia.
      In all patients, significant eosinophilia and, in some instances, bone marrow
      fibrosis developed. In addition to the increase in the number of circulating
      neutrophilic granulocytes, platelets, and reticulocytes, an increase of
      peripheral blood monocytes and lymphocytes was observed. The histologic and
      cytologic findings support the concept that rhIL-3 stimulates the proliferation
      and differentiation of pluripotent hematopoietic progenitor cells. It appears to
      be a safe and efficient therapeutic modality in patients with bone marrow
      failure. Additional clinical studies are needed to determine which patients will
      profit most from rhIL-3 treatment.

PMID- 1996547
TI  - Laboratory and clinical evaluation of white blood cell differential counts.
      Comparison of the Coulter VCS, Technicon H-1, and 800-cell manual method.
AB  - Eight hundred-cell manual white blood cell differential count evaluations of
      Coulter VCS and Technicon H-1 included estimates of accuracy, imprecision, random
      and systematic errors, clinical relevance, and detection of immature neutrophils.
      Accuracy was acceptable, except for H-1 testing of monocytes. Instrument
      imprecision was similar, except for tighter monocyte values as measured by the
      VCS. Deming regression determined random errors were greater for H-1 monocytes
      and proportional errors were similar. Constant errors for the VCS were less than
      the H-1 for neutrophils and monocytes and greater than the H-1 for eosinophils
      and lymphocytes. H-1 morphologic false-negative rates were twice those for VCS.
      True-positive and false-negative rates in cases with immature neutrophils were
      70.6% and 20.3% for the VCS and 35% and 55.9% for the H-1. The reference false
      positive rate was 4.4%. Clinically appropriate VCS flags were generated in
      distributionally abnormal cases. Predictive values were higher for the VCS.

PMID- 1996546
TI  - Flow cytometric analysis of terminal deoxynucleotidyl transferase.
AB  - Terminal deoxynucleotidyl transferase (TdT) is a useful marker for lymphoid
      precursor cells. In this study, the authors used flow cytometry (FCM) to analyze
      TdT expression in human hematopoietic malignancies. Cells were fixed in 0.5%
      formaldehyde, briefly exposed to nonionic detergent, and subsequently labeled
      with mouse monoclonal anti-TdT antibodies followed by fluorescein-conjugated
      antimouse IgG and propidium iodide (PI), which was used for the simultaneous
      analysis of DNA content. Cells from 20 of 22 acute lymphoblastic leukemias (ALL),
      4 of 7 mixed lineage leukemias, 2 of 21 acute myeloid and myelomonocytic
      leukemias, 1 of 2 chronic myeloid leukemias in blast crisis, 1 lymphoblastic
      lymphoma, and 1 thymoma were TdT positive. Cells from 13 nonlymphoblastic
      lymphomas, 3 myelodysplastic bone marrows, and peripheral blood mononuclear cells
      from 29 normal individuals were negative. An excellent correlation was seen
      between this assay, the conventional slide immunofluorescence technique, and an
      enzyme immunoassay method. The FCM assay detected as few as 2% blasts in mixing
      experiments of TdT-containing leukemic cells with normal peripheral lymphocytes.
      Furthermore, the combined analysis of TdT and DNA allowed the recognition of
      aneuploid TdT positive cells in four cases of ALL. The high sensitivity, the
      quantitative information obtained, and the capability of simultaneously analyzing
      DNA content make this method of TdT analysis more valuable than conventional
      techniques.

PMID- 1996548
TI  - The use of LIS for blood usage review. Experience in a children's hospital.
AB  - To comply with the requirements of the Joint Commission for the Accreditation of
      Healthcare Organizations (JCAHO) and to facilitate the review process, the
      authors designed a program to screen for the appropriateness of packed red cell
      (PRC) and platelet concentrate (PLT) transfusions. The purpose of this report is
      to describe the methodology of the review process. A quality assurance (QA)
      monitor was created in the Laboratory Information System (LIS) to screen
      indicators: hemoglobin for PRCs and platelet count for PLTs. Numerical value
      limits were defined to determine acceptable ranges. Each week, the LIS compiles a
      list of all patients who received transfusions and for whom the QA monitor
      determined that the values of the screened indicators were outside the defined
      appropriate limits. A detailed transfusion record is generated for each patient
      identified. During a six-month evaluation of this program, a total of 1,788 PRC
      and 3,109 PLT units were transfused. Of these, 582 PRC (32.5%) and 2,219 PLT
      (71.4%) units were within the acceptable guidelines. Lists for the remaining
      1,206 PRCs and 890 PLTs were generated. Review of the transfusion record and
      other laboratory values from the LIS established the appropriateness of 1,052 PRC
      and 782 PLT transfusions. At the conclusion of the six-month period, the medical
      charts for 181 (11%) PRC and 108 (4.5%) PLT transfusions required chart review.
      This method provided major reduction in time of the transfusion review process.
      Similar guidelines may be used to monitor other transfusion products such as
      fresh frozen plasma.

PMID- 1996549
TI  - Ceftazidime-induced hemolysis in a patient with drug-dependent antibodies
      reactive by immune complex and drug adsorption mechanisms.
AB  - A 35-year-old woman developed acute intravascular hemolysis within five days of
      beginning a course of ceftazidime. The direct antiglobulin test became strongly
      positive with both anti-IgG and anticomplement. The serum contained an antibody
      that, in the presence of ceftazidime, sensitized unmodified reagent cells with
      IgG and complement (immune-complex type). The serum also agglutinated ceftazidime
      pretreated cells at room temperature and 37 degrees C (drug-adsorption type).
      Retrospective testing disclosed that the drug adsorption antibody, which had been
      present before the current course of antibiotics, was not demonstrable during the
      hemolysis. The reactivity of the immune complex antibody, which developed by the
      second day of ceftazidime, paralleled the degree of hemolysis and the strength of
      the direct antiglobulin test. The authors believe that this patient had two
      separate ceftazidime-dependent antibodies and that the antibody reactive by
      immune complex mechanism mediated an episode of acute intravascular hemolysis.

PMID- 1996550
TI  - Issues in cerebrospinal fluid management. CSF Venereal Disease Research
      Laboratory testing.
AB  - Three policies for decreasing unnecessary cerebrospinal fluid (CSF) management
      Venereal Disease Research Laboratory (VDRL) tests were compared. The first policy
      attempted to educate physicians about the use of serologic tests for diagnosing
      neurosyphilis but allowed the CSF VDRL to be performed either as a screening test
      or as a retrospective test. The second policy required that the CSF VDRL be
      performed as a retrospective test without regard to the patient's serologic
      status. The third policy required that a patient be seropositive by either rapid
      plasma reagin (RPR) or fluorescent treponemal antibody absorbance (FTA-ABS)
      before a CSF VDRL could be performed. Before these policies were instituted, VDRL
      testing was performed on 18.2% of all CSF samples. The optional and required
      retrospective policies decreased the CSF VDRL rate to 13.0% and 8.5%,
      respectively, but the percentages of seropositive patients for whom these
      procedures were performed were only 7.3% and 12.9%. The third policy decreased
      the CSF VDRL test rate to 1.8% (P less than 0.001) with seropositivity improving
      to 90%. To assure serologic tests are obtained in the evaluation of
      neurosyphilis, requirement for seropositivity must be implemented with the use of
      retrospective CSF VDRL testing.

PMID- 1996551
TI  - Serum enzyme alterations in chronic muscle disease. A biopsy-based diagnostic
      assessment.
AB  - The results of interpretation of muscle biopsies were compared retrospectively to
      activities of serum enzymes and isoenzymes. A total of 137 patients seen at the
      Cleveland Clinic Foundation in 1986 and 1987 were included in this study. Serum
      enzymes evaluated were CK, AST, LD, and aldolase (ALS), as well as the percentage
      CK-MB isoenzyme. The units of CK-MB and the ratios of CK to AST, LD, and ALS were
      calculated. Descriptive statistics, Kruskal-Wallis one-way analysis of variance,
      and stepwise logistic regression were performed. A diagnostic algorithm was
      constructed using a computer-assisted rule generation program. Myopathic diseases
      yielded a greater mean increase in serum enzyme activity than atrophic diseases.
      By multivariate stepwise logistic regression, increases in serum AST and CK
      activity were independently associated with the presence of inflammation in a
      muscle biopsy specimen. The diagnostic algorithm allowed for the separation of
      myopathies from atrophies and could identify cases of Duchenne's muscular
      dystrophy and polymyositis.

PMID- 1996552
TI  - Antivenom therapy in Russell's viper bite.
AB  - Bleeding and renal failure are the two main manifestations responsible for the
      high morbidity and mortality in untreated Russell's viper bite victims. This
      study was an effort to find prognostic factors and a practical therapeutic
      approach for the care of such patients. Early detection of abnormalities in the
      clot quality test and/or evidence of systemic bleeding followed by immediate
      correction of the clotting defects using specific antivenom can reduce morbidity
      in Russell's viper envenomation.

PMID- 1996553
TI  - Issues in cerebrospinal fluid management. Acid-fast bacillus smear and culture.
AB  - Meningeal tuberculosis is an uncommon disease in the United States with an annual
      incidence of fewer than 200 cases. This study evaluates three approaches to
      improving the use of the cerebrospinal (CSF) acid-fast bacillus (AFB) smear and
      culture procedure: (1) education alone; (2) optional screening by which
      physicians can select to have the AFB analysis stopped if the initial CSF
      findings are unremarkable; and (3) mandatory screening before the performance of
      all CSF AFB analyses. With education alone, the CSF AFB culture rate decreased
      from 20.6% of all CSF acquisitions to 15.7% (P less than 0.001); however, the
      effect may have been related to a decrease in all types of AFB testing. Optional
      screening had no impact on the AFB testing rate. Mandatory screening
      significantly decreased the CSF AFB rate to 6.7% (P less than 0.001), unrelated
      to changes in other types of AFB testing. Laboratories that employ mandatory
      screening should report the screening results immediately and have a mechanism
      whereby physicians can bypass the screen, providing CSF AFB analysis on
      unremarkable fluid from high-risk patients.

PMID- 1996554
TI  - Rapid microscopic detection of malaria parasites permanently fluorochrome stained
      in blood smears with aluminum and morin.
AB  - Intra- and extracellular Plasmodium parasites in fixed blood smears are easily
      identifiable by fluorescence microscopy after brief mordanting with aluminum
      ammonium sulfate and staining with morin (3,5,7,1',4'-pentahydroxyflavanol). The
      intensely fluorescent preparations of stained parasites are strongly resistant to
      photodegradation and remained essentially unimpaired for two years.

PMID- 1996555
TI  - Case report of plasma cell myeloma.

PMID- 1996556
TI  - Abnormal proteolytic degradation of von Willebrand factor after desmopressin
      infusion in a new subtype of von Willebrand disease (ID).
AB  - We describe two members of a single family, father and son, with mild factor XII
      deficiency associated to von Willebrand disease (vWD) with aberrant structure in
      whom distinct multimeric abnormalities and an abnormal proteolytic processing of
      von Willebrand factor (vWF) after desmopressin (DDAVP) administration were
      present. They had a mild bleeding history, low levels of vWF-related activities,
      and a prolonged bleeding time. Low-resolution agarose gel electrophoresis showed
      a vWF with all size multimers in plasma and platelets. Higher-resolution agarose
      gels demonstrated that the main band was present, but the relative proportion of
      the satellite bands was markedly reduced. The smallest oligomer was not
      increased. After the infusion of DDAVP to the father, a transient increase in the
      relative proportion of the satellite bands was seen, as described in normal
      individuals. No difference in the structure of vWF was observed when blood was
      collected with proteinase inhibitors. The analysis of native subunits of vWF and
      their proteolytic derived fragments, after DDAVP administration, showed a
      temporary augmentation of the 176 kDa fragment, as seen in normal subjects, as
      well as an increase of the 189 kDa fragment. This finding had not been reported
      previously either in normal individuals or in patients with vWD.

PMID- 1996557
TI  - High-dose dexamethasone for refractory or relapsing multiple myeloma.
AB  - In order to assess the efficacy and toxicity of dexamethasone as a single agent
      without the concomitant infusion of Adriamycin and vincristine (VAD), an ECOG
      pilot study was initiated using 40 mg by mouth daily for 4 days every week for 8
      weeks. Patients who responded were then maintained on the same treatment, but at
      2 week intervals. Of the 32 patients evaluable for response, three were
      completely refractory to all prior therapy. All patients had advanced disease and
      26 had received multiple prior treatments. There were 13/32 (40%) objective
      responses by ECOG criteria. Of the 28 patients evaluable for subjective response,
      i.e., significant decrease in performance status and/or bone pain, eight (28.5%)
      responded. Of the 34 patients evaluable for toxicity, 19 patients (55%) had
      moderate to severe side effects, including nine who had central nervous system
      effects, three who had gastrointestinal bleeding, two who had pulmonary emboli,
      one with psychosis, and four who had serious infections with one death. Median
      survival for the entire group was 19 weeks, with 31 weeks in the responders and 9
      weeks in the non-responders. Although high-dose dexamethasone is capable of
      producing a significant number of partial responses (40%), it is associated with
      excessive toxicity. Less frequent administration of the dexamethasone at 2 week
      intervals was well tolerated in the maintenance of partial response, but has not
      been studied for efficacy in induction of remission.

PMID- 1996558
TI  - Effect of beta-globin gene cluster haplotype on the hematological and clinical
      features of sickle cell anemia.
AB  - In 113 black American adults with sickle cell anemia (HbSS), we examined nine
      polymorphic restriction sites, including the Xmnl site 5' to the G gamma gene, to
      see whether haplotype is related to the level of HbF and the proportion of G
      gamma chains or if it influences the hematological and clinical features of the
      disease. Seventy-five percent of the patients were homozygous or heterozygous for
      the Benin (no. 19) or Central African Republic (Bantu, no. 20) haplotypes; 13.3%
      were homozygous or heterozygous for the Senegal (no. 3) haplotype, while 11.5%
      had other genotypes. Of the subjects, 14.2% were either homozygous or
      heterozygous for the Xmnl restriction site 5' to the G gamma gene. We found no
      effect of haplotype on HbF levels. The level of G gamma chains was 60.5% +/-
      17.0% in individuals heterozygous or homozygous for haplotype no. 3 and was 46.9%
      +/- 11.6% in individuals with other haplotypes. Subjects with the Xmnl site 5' to
      the G gamma gene had G gamma globin levels of 59.5% +/- 16.7% while those lacking
      that site had an average of 47.2% +/- 12.1%. There were no significant
      differences among these groups in hemoglobin concentration, packed cell volume,
      mean cell volume, or clinical indicators of vaso-occlusive severity, including
      crises, hospitalizations per year, aseptic bone necrosis, acute chest syndrome,
      or leg ulcers. While the presence of haplotype 3 and the 5' G gamma Xmnl site
      were associated with increased G gamma chains, there was no effect on HbF level
      or other hematological and clinical features that might reflect disease severity.
      It is likely that determinants unrelated to haplotype, linked or unlinked to the
      beta-globin gene cluster, are the major effectors of differences in the levels of
      HbF in American patients with sickle cell anemia.

PMID- 1996559
TI  - GM-CSF-mediated impairment of liver to synthesize albumin, cholinesterase, and
      cholesterol.
AB  - Serum albumin, cholinesterase, and cholesterol were measured in ten patients with
      aplastic anemia and eight with myelodysplastic syndrome who received the
      administration of recombinant human GM-CSF. Serum albumin, cholinesterase, and
      cholesterol were significantly lowered by the administration of GM-CSF and
      recovered after the cessation of GM-CSF. These data suggest that GM-CSF impairs
      the biosynthesis of liver cells and that cholesterol-lowering activity of GM-CSF,
      which is previously reported, is due to the impairment of liver biosynthesis by
      GM-CSF.

PMID- 1996560
TI  - CD71 phenotype and the value of gallium imaging in lymphomas.
AB  - Tumor cells of 14 cases of non-Hodgkin lymphomas and 2 cases of Hodgkin disease
      were tested for the presence of the transferrin receptor (CD71) by flow
      cytofluorimetry before 67gallium imaging. It appeared that expression of CD71
      phenotype was closely related to the positivity of gallium scan before therapy.
      We feel that this test is able to predict the avidity for 67gallium and the
      clinical implications are discussed.

PMID- 1996561
TI  - Cyclosporine for the treatment of granulocytopenia in Felty's syndrome.
AB  - A patient with Felty's syndrome was treated with cyclosporine, initially 10
      mg/kg/day and then 4 mg/kg/day. The neutrophil count increased by 6 weeks and was
      normal at 3 months. Over the subsequent 27 months the neutrophil count was
      closely related to the cyclosporine dosage and there was no evidence of
      cyclosporine toxicity. This case indicates that cyclosporine may have a role in
      the treatment of Felty's syndrome.

PMID- 1996563
TI  - A case of plasma cell leukemia superimposed on Philadelphia (Ph) chromosome
      positive chronic myelogenous leukemia.

PMID- 1996562
TI  - Essential thrombocythemia and complications of pregnancy.

PMID- 1996564
TI  - Immunotactoid glomerulopathy.
AB  - During the past 10 years, immunotactoid glomerulopathy has become recognized with
      increasing frequency. The lesion is characterized histologically by highly
      organized ultrastructural deposits that appear to be composed of immunoglobulin
      and complement and are negative for amyloid by Congo red stain. Clinically and/or
      serologically, patients have no evidence of cryoglobulinemia, amyloidosis,
      systemic lupus erythematosus, or a paraproteinemia, disorders associated with
      glomerular deposits, which also have a highly organized tactoidal or fibrillar
      characteristic. Immunotactoid glomerulopathy does not appear to be a
      multisystemic disease process and thus may represent a primary glomerulopathy.
      Patients with immunotactoid glomerulopathy present with proteinuria (nephrotic
      range in more than 60%) and over half of the patients have hypertension,
      hematuria, and renal insufficiency. Progression to end stage renal disease has
      occurred in more than 40% of patients reported to date. The experience in
      treating this disorder using prednisone and/or immunosuppression is limited and
      has not been impressive. Four patients have successfully undergone renal
      transplantation, but proteinuria recurred in two and was associated with the
      recurrence of immunotactoid glomerulopathy in the renal allograft. Although we
      have gained insight into the clinical course and histopathology of this disorder
      over the past few years, we still know little about its pathogenesis, an area for
      further research.

PMID- 1996565
TI  - Of rats and men: the need for more convincing clinical studies on progression of
      renal diseases.

PMID- 1996566
TI  - Prolonged survival with a remnant kidney.
AB  - Surgical ablation of five-sixths renal mass in Munich-Wistar rats fed a high
      protein diet leads to focal sclerosis in the remnant kidney and progressive renal
      failure. Experimental data suggest that this injury results from intraglomerular
      hypertension and/or chronic glomerular hyperfiltration. Data in humans largely
      are limited to patients with unilateral renal agenesis or uninephrectomy, either
      for unilateral renal disease or for kidney transplant donation. Isolated case
      reports have documented focal sclerosis and progressive renal failure in two
      patients with a remnant kidney. To obtain data in humans with a remnant kidney,
      we surveyed more than 800 urologists and nephrologists in the United States and
      abroad. Criteria for inclusion in the study were (1) surgical resection (in one
      or more operations) resulting in the presence of a remnant kidney; and (2) an
      adequate period of follow-up, defined as 5 years or greater. A total of 13
      patients were identified (from 13 different centers). Twelve patients had renal
      cancer and one had tuberculosis. Six patients were observed for 10 or more years
      postoperatively and all have stable serum creatinine levels of less than 270
      mumol/L (3.0 mg/dL); two of these six patients are now more than 25 and 30 years
      postoperation. The other seven patients, observed for 5 to 7 years, have serum
      creatinine levels less than 270 mumol/L (3 mg/dL), while one has an increasing
      serum creatinine level. The two longest surviving patients both have undergone
      successful pregnancy with no overall change in serum creatinine. These
      observations demonstrate that it is possible for humans to survive more than 30
      years with a stable serum creatinine, despite the presence of only a remnant
      kidney.

PMID- 1996567
TI  - Renal function after tumor enucleation in a solitary kidney.
AB  - Whether extensive ablation of renal mass in humans leads to progressive
      glomerulosclerosis, proteinuria, and hypertension, as it does in animal models,
      is a matter of controversy. We have studied kidney function in six patients who
      underwent enucleation of a renal cell carcinoma in a solitary kidney. Four
      patients had previously had a nephrectomy. The two others each had one atrophic,
      nonfunctioning kidney. Serum creatinine levels before surgery were within the
      normal range (mean, 99.9 mumol/L [1.13 mg/dL]). Two weeks after tumor
      enucleation, creatinine levels were significantly higher than the preoperative
      values (mean, 124.6 mumol/L [1.41 mg/dL]). The follow-up period varied from 10 to
      23 months. In all patients, kidney function improved during the following months.
      Serum creatinine levels nearly reached preoperative values in all patients (mean,
      105.2 mumol/L [1.19 mg/dL]). None of the patients showed a progressive
      deterioration in renal function or proteinuria. We found a modest increase in
      blood pressure in two patients who had been normotensive before surgery. In
      conclusion, tumor enucleation in a solitary kidney did not cause significant
      renal injury to the remnant kidneys in our patients, at least in the short term.

PMID- 1996568
TI  - Reactive oxygen species production by monocytes and polymorphonuclear leukocytes
      during dialysis.
AB  - Intradialytic production of reactive oxygen species (ROS) by monocytes and
      polymorphonuclear leukocytes (PMNL) was examined separately in six hemodialysis
      patients. Samples obtained 15 minutes after initiation of dialysis with new
      cuprophane membranes demonstrated significantly increased (P less than 0.05) ROS
      production in both cell populations as measured by the fluorescence of a specific
      intracellular marker (2',7'-dichlorofluorescein diacetate [DCFH-DA]) assayed by
      flow cytometry. Granulocytes harvested during dialysis also showed decreased
      responsiveness to exogenous C5a and F-Met-Leu-Phe (FMLP) at 15, 30, and 60
      minutes after initiation of dialysis (P less than 0.05). Our data suggest that
      hemodialysis with cuprophane membrane is associated with monocyte and PMNL
      activation as shown by production of ROS coincident with peak activation of the
      complement cascade; these granulocytes become refractory to further stimulation
      with C5a and FMLP during dialysis.

PMID- 1996570
TI  - Hemodynamic effects of partial correction of chronic anemia by recombinant human
      erythropoietin in patients on dialysis.
AB  - Eighteen patients on chronic hemodialysis with renal anemia were treated with
      recombinant human erythropoietin (r-HuEPO). Hemodynamic parameters in the resting
      state were determined before and after successful treatment. Posttreatment
      cardiac index was decreased (3.3 v 2.8 L/min/m2), whereas diastolic blood
      pressure (72 v 79 mm Hg) and calculated peripheral resistance (2,230 v 2,860
      dyne.cm.s-5) were increased significantly when compared with the pretreatment
      period. We conclude from our study that the increase of blood pressure as seen in
      patients on dialysis, who are effectively treated with r-HuEPO, is due to an
      increase in peripheral resistance. This increase overrules the decrease of
      cardiac index and might well be a result of peripheral vasoconstriction due to
      improved oxygen availability.

PMID- 1996569
TI  - Dialysis-induced alterations in left ventricular filling: mechanisms and clinical
      significance.
AB  - Quantitative two-dimensional (2-D) and Doppler echocardiography were used to
      determine whether hemodialysis results in alterations in left ventricular (LV)
      diastolic filling that might contribute to dialysis-induced hypotension, as well
      as to assess whether any hemodynamic variables or indices of diastolic filling
      might be used to identify which patients were at the greatest risk of becoming
      hemodynamically unstable during dialysis. Sixteen male patients undergoing
      routine maintenance hemodialysis for end-stage renal disease were prospectively
      studied before and after hemodialysis. Following hemodialysis there was a
      significant prolongation (P less than 0.05) in LV isovolumetric relaxation time
      (IVRT), as well as a significant reduction in the rate and extent of early rapid
      ventricular filling (P less than 0.005); in contrast, late atrial-assisted
      filling did not change significantly. A multiple stepwise linear regression
      analysis of predialysis hemodynamic parameters and noninvasive indices of LV
      filling showed that there was a significant independent inverse relationship
      between the frequency of dialysis-related hypotensive episodes and the duration
      of early LV filling (r = -0.81; P less than 0.001). These results suggest that
      hemodialysis results in discrete alterations in early LV filling, with no
      significant compensatory increase in late atrial-assisted ventricular filling.
      Further, patients with the shortest early LV filling times appeared to have the
      greatest predilection for becoming hemodynamically unstable during dialysis.

PMID- 1996571
TI  - Evaluation of hemodialysis patients treated with erythropoietin.
AB  - We evaluated 20 hemodialysis patients who had been treated with erythropoietin
      (Epo). All patients had hemoglobin levels below 8.5 g/dL. They were randomized to
      receive either Epo (100 U/kg) or placebo three times per week for 12 weeks. All
      patients on Epo had a significant (P less than 0.001) elevation of hematocrit
      levels (19.7% v 35.7%). They also had a significant (P less than 0.05) increase
      in midweek predialysis blood urea nitrogen (BUN) levels, 27.8 versus 29.6 mmol/L
      (78 v 83 mg/dL), and serum phosphorus, 1.8 versus 2.1 mm/L (5.7 v 6.6 mg/dL).
      Protein catabolic rate also increased significantly (P less than 0.05). No
      changes were seen in the levels of serum creatinine and potassium, but episodes
      of hyperkalemia were more frequent in patients on Epo. No changes were seen in
      patients on placebo. When hematocrit increased, the clearance of blood-water for
      urea decreased 9%, and the clearance of creatinine, potassium, and phosphorus
      decreased 15%. Patients on Epo increased both their appetite and protein intake.
      More frequent episodes of hyperkalemia and elevated phosphorus level resulted
      from a combination of increased intake and decreased dialyzer clearance. We may
      need blood-water clearance to calculate Kt/V.

PMID- 1996573
TI  - Use of the fistula assessment monitor to detect stenoses in access fistulae.
AB  - Twenty-three unselected hemodialysis patients with functioning access
      arteriovenous fistulae were studied prospectively to determine the best technique
      for detecting stenoses within the fistulae. Combined clinical assessment and
      fistula assessment monitoring were compared with transbrachial angiography.
      Fistula assessment monitoring was more accurate (96%) than combined clinical
      assessment (accuracy, 52%) in stenosis detection. Complications of angiography
      occurred in 17% of patients; there were no complications of fistula assessment
      monitoring. Fistula assessment monitoring was better than combined clinical
      assessment in predicting clinical outcome for arteriovenous fistulae over 6
      months and was as good as angiography. Routine fistula assessment monitoring
      could reduce inappropriate angiography and detect clinically significant silent
      stenoses. It is an ideal method for monitoring arteriovenous access fistulae.

PMID- 1996572
TI  - Quantitating hemodialysis: a comparison of three kinetic models.
AB  - Three urea kinetic analyses were applied to hemodialysis and their conformity
      assessed. Sixteen patients underwent 50 measurements of dialyzer clearance (K),
      protein catabolic rate (PCR), and dialysis quantification (Kt/V) using the urea
      kinetic model (UKM) of Gotch and Sargent, Malchesky's direct dialysis
      quantification (DDQ), and the graphic technique of urea reduction analysis (URA)
      devised by Keshaviah. Additionally, the equations proposed by Jindal (percent
      urea reduction), and Daugirdas were used to calculate Kt/V values for each study.
      Dialyzer performance determined by whole blood urea clearance consistently
      exceeded simultaneous dialysate urea removal and was 55% greater than the
      clearance calculated by DDQ. Despite these variations, dialysis adequacy (Kt/V)
      and normalized protein catabolic rate (nPCR) were remarkably constant when
      derived by fixed-volume single-pool analyses (ie, UKM, DDQ, and URA). Application
      of variable-volume corrections increased Kt/V and nPCR, but caused DDQ values to
      diverge from those of UKM and URA. During rapid high-efficiency dialysis (RHED),
      the UKM predicted urea removal in excess of that documented by DDQ. During this
      trial (low-level RHED with K = 2.98 mL.kg-1 per min), urea dysequilibrium across
      blood-cell interfaces was sufficient to cause UKM to overestimate protein
      catabolism by 5%. The basic assumption of single-pool kinetics may be
      inappropriate during RHED, and further increases in dialyzer clearance will
      increase the discrepancy between projected and actual urea removal. Future
      comparisons of RHED prescriptions should employ mass balance data, or redesigned
      kinetic analyses.

PMID- 1996574
TI  - Effect of intraperitoneal fluid volume changes on esophageal pressures: studies
      in patients on continuous ambulatory peritoneal dialysis.
AB  - Esophageal manometric studies were performed in 11 patients on continuous
      ambulatory peritoneal dialysis (CAPD) with the dialysis fluid in the peritoneal
      cavity, after emptying and again after reinfusion. No systematic changes were
      found in intragastric or lower esophageal sphincter (LES) pressures at any time.
      No differences in mean distal esophageal amplitude (DEA), duration, or velocity
      of peristalsis were noted. Although upper gastrointestinal problems are common in
      CAPD patients and were reported by eight of 11 patients, this study suggests that
      these symptoms cannot be explained by changes in gastric and esophageal
      pressures.

PMID- 1996575
TI  - Plasma terminal complement complexes in acute poststreptococcal
      glomerulonephritis.
AB  - In most instances of acute poststreptococcal glomerulonephritis (APSGN),
      activation of the complement system occurs, as reflected by decreased levels of
      the complement proteins C3, C5, and properdin (P). Recent studies implicate
      terminal complement complexes (TCC) in the pathogenesis of glomerular injury. The
      fluid phase TCC, SC5b-9, reflects the formation of membrane-bound C5b-9 and has
      been used as a clinical marker in various diseases. Plasma concentrations of SC5b
      9 were measured with an enzyme immunoassay using a monoclonal antibody to a
      neoantigen expressed on the SC5b-9 complex in 13 children who presented with
      clinical and pathologic features of APSGN. SC5b-9 was significantly elevated in
      all plasmas obtained within 30 days after onset of clinical glomerulonephritis.
      Concentrations of SC5b-9 in acute plasmas were significantly higher than those of
      paired convalescent samples. For individual patients, as SC5b-9 concentration
      returned to normal there was a coincident decrease in serum creatinine
      concentration and urinary protein excretion, signifying clinical improvement in
      glomerulonephritis. Thus, TCC generation commonly occurs in the early stages of
      APSGN and may be of importance in the pathogenesis of the condition.

PMID- 1996576
TI  - Low-protein diet and glomerular size-selective function in membranous
      glomerulopathy.
AB  - We studied the effect of dietary protein restriction on glomerular function and
      proteinuria in nine patients with membranous nephropathy. Patients were randomly
      assigned to a 3-month period of a normal protein diet (NPD, 1.3 mg/kg/d) or of a
      low-protein diet (LPD, 0.6 mg/kg/d), in a cross-over design. Dietary protein
      restriction did not affect glomerular filtration rate (47.8 +/- 10.7 and 49.0 +/-
      13.5 mL/min/1.73 m2, LPD and NPD, respectively) and renal plasma flow (456 +/-
      119 and 499 +/- 161 mL/min/1.73 m2, LPD and NPD, respectively), nor did it
      significantly improve glomerular permselective function, as shown by urinary
      protein excretion (3.1 +/- 2.2 and 3.5 +/- 2.8 g/d, LPD and NPD, respectively)
      and fractional clearance of albumin, IgG, and neutral dextran molecules of graded
      molecular size (radii ranging from 2.8 to 6.0 nm). These results indicate that
      reduction of protein intake to 0.6 g/kg/d does not improve glomerular size
      selectivity in membranous nephropathy. Thus, in current clinical practice, a
      protein-restricted diet does not appear to be effective in reducing proteinuria
      in this category of patients.

PMID- 1996577
TI  - Hypercalciuria in parathyroid disorders: effect of dietary sodium control.
AB  - Moderate dietary Na restriction (80 mmol/d for 7 days) during constant Ca intake
      can reduce high urinary Ca excretion to normal levels in idiopathic
      hypercalciuria (IH). A similar protocol was used to test its effect in primary
      hyperparathyroidism (PHPT) and also in hypoparathyroid subjects (HOPT) during
      treatment with dihydrotachysterol (DHT). Nine subjects with PHPT, 10 with HOPT,
      and one with pseudo-HOPT were evaluated after Na-restricted (80 mmol/d) and Na
      supplemented (200 mmol/d) diets for 7 days each with dietary Ca constant. Na
      restriction resulted in a decrease in mean urinary 24-hour Ca excretion in PHPT
      subjects (10.6 v 7.6 mmol/d [424 v 304 mg], P less than 0.0001) and in one pseudo
      HOPT subject, similar to the pattern seen previously in IH subjects. In contrast,
      Na restriction was not accompanied by significant change in Ca excretion in HOPT.
      There was no change in serum immunoreactive PTH (iPTH) or 1,25(OH)2 vitamin D
      levels in either group when Na intake was altered. Thus, the presence of
      parathyroid hormone (PTH) is necessary for sodium-related alterations in urinary
      Ca to occur. The effect of PTH appears to be "permissive" rather than "active."
      Dietary Na restriction may have a role in the management of hypercalciuria in
      mild PHPT cases when parathyroidectomy is contraindicated.

PMID- 1996578
TI  - Nephrotic proteinuria without hypoalbuminemia: clinical characteristics and
      response to angiotensin-converting enzyme inhibition.
AB  - Although hypoalbuminemia is a fundamental characteristic of nephrotic syndrome
      (NS), there are many patients with massive proteinuria that do not develop
      hypoalbuminemia. We have studied the clinical and biochemical characteristics of
      19 patients with persistent massive proteinuria (greater than 5 g/d) and normal
      serum albumin (group I) in comparison with 16 patients with similar proteinuria
      excretion, but persistent hypoalbuminemia (group II). Most of group I patients
      had diagnoses suggesting glomerular hyperfiltration (focal glomerulosclerosis
      [FGS] associated with vesicoureteral reflux [VUR], reduction of renal mass,
      proteinuria associated with obesity, sclerotic phase of idiopathic crescentic
      glomerulonephritis [GN] in contrast with those of group II, in which membranous
      GN was the most frequent diagnosis. We prospectively investigated differences in
      the antiproteinuric effect of captopril, an antiotensin-converting enzyme
      inhibitor (ACEI); after 6 months of treatment, proteinuria decreased clearly in
      group I (7.1 +/- 1.7 to 3.7 +/- 1.7 g/d; P less than 0.001), whereas no
      significant changes were observed in group II (8.1 +/- 2.4 to 8.8 +/- 4 g/d).
      Serum creatinine (Scr) remained stable during captopril treatment in group I,
      whereas three patients in group II showed a worsening of renal function.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1996579
TI  - Acute glomerulonephritis in a patient with Rocky Mountain spotted fever.
AB  - It is generally assumed that acute tubular necrosis is the etiology of renal
      failure that can occur during the course of Rocky Mountain spotted fever (RMSF).
      However, histologic examination of kidneys has been mainly limited to autopsy
      cases of fulminant infections. Acute glomerulonephritis due to glomerular immune
      complex deposition has not been reported in RMSF. We describe a case of acute
      oliguric renal failure that developed more than 2 weeks following the onset of
      RMSF. Renal biopsy showed acute glomerulonephritis with inflammatory cell
      infiltration and subendothelial immune deposits. Thus, acute glomerulonephritis
      should be in the differential diagnosis of acute renal failure that occurs in
      RMSF.

PMID- 1996580
TI  - Cyclosporine-induced thrombotic microangiopathy resulting in renal allograft loss
      and its successful reuse: a report of two cases.
AB  - Cyclosporine-induced thrombotic microangiopathy is a rare complication of renal
      transplantation. It commonly leads to graft loss. The mechanism of this entity is
      unknown. Factors intrinsic to the donor kidney appear to play an important role.
      We describe two cases of renal transplant patients who lost their first grafts
      secondary to cyclosporine-induced thrombotic microangiopathy. These patients were
      successfully retransplanted with an immunosuppressive protocol that included long
      term cyclosporine. We conclude that graft loss from this entity is not a
      contraindication to subsequent successful transplantation with cyclosporine.

PMID- 1996581
TI  - Membranous nephropathy in a patient with renal cell carcinoma.

PMID- 1996582
TI  - Universal precautions for preventing occupational exposures to human
      immunodeficiency virus type 1.

PMID- 1996583
TI  - Frequency of nonparenteral occupational exposures to blood and body fluids before
      and after universal precautions training.
AB  - PURPOSE: During annual periods before and after Universal Precautions training,
      we compared the frequency of health care workers' self-reported cutaneous
      exposures to blood and various body substances from any patient and from patients
      presumed infected with human immunodeficiency virus type 1 (HIV-1). SUBJECTS AND
      METHODS: Self-reported cutaneous exposures to blood, sputum, urine, feces, and
      other body substances were evaluated separately in 559 workers during the first
      survey and 269 workers during the second. RESULTS: Mean annual blood exposures
      decreased from 35.8 to 18.1, and mean annual exposures to all substances
      decreased from 77.8 to 40.0 (p less than 0.001 for both determinations). Two
      matched analyses of a subset of 200 participants who completed both surveys had
      similar results. Reported exposures to blood, presumably infectious blood,
      sputum, presumably infectious sputum, and urine were significantly decreased.
      Participants were tested for antibodies to HIV-1; no participant reporting
      cutaneous exposures acquired HIV-1 infection. The upper bound for the 95%
      confidence interval for the risk of HIV-1 infection associated with a single
      cutaneous exposure was 0.04% for blood presumed to contain HIV-1 and 0.02% for
      any body substance presumed to contain HIV-1. CONCLUSIONS: These data suggest
      that Universal Precautions training significantly decreased but did not eliminate
      cutaneous exposures to blood and body substances. The results further suggest
      that the risk for HIV-1 infection associated with cutaneous exposures is
      substantially lower than the risk associated with parenteral exposures.

PMID- 1996585
TI  - Combined hepatic and renal transplantation in primary hyperoxaluria type I:
      clinical report of nine cases.
AB  - PURPOSE AND PATIENTS AND METHODS: The purpose of this article is to report the
      experience of three centers with combined hepatic and renal transplantation for
      pyridoxine-resistant primary hyperoxaluria type I (alanine:glyoxylate
      aminotransferase [EC 2.6.1.44] deficiency), with particular emphasis on the
      selection criteria and timing of the operation. Nine patients with this inherited
      disease were treated by combined hepatic and renal transplantation. The former
      replaces the enzyme-deficient organ while the latter replaces the functionally
      affected organ. RESULTS: One patient with gross systemic oxalosis died in the
      immediate postoperative period and another died 8 weeks postoperatively of a
      generalized cytomegalovirus infection, having shown evidence of biochemical
      correction. One patient with particularly severe osteodystrophy at the time of
      the operation died 14 months postoperatively from renal failure due to
      progressive calcium oxalate nephrocalcinosis involving the transplanted kidney,
      plus thromboembolic disease. He also had very extensive systemic oxalosis. An
      additional patient with severe osteodystrophy died 9 months postoperatively. One
      patient developed hyper-rejection of the kidney and died later of
      gastrointestinal hemorrhage. The four long-term survivors (22 to 38 months) have
      remained asymptomatic from the standpoint of their renal disease, with resolution
      of any manifestations of systemic oxalosis that they may have had. They are
      either employed or continuing their education. CONCLUSIONS: A prolonged period of
      end-stage renal failure treated by dialysis regimens that are suitable for non
      hyperoxaluric renal failure and extensive systemic oxalosis, particularly
      oxalotic osteodystrophy, are poor prognostic features. We propose that hepatic
      transplantation should be considered as definitive treatment before end-stage
      renal failure develops. This should be supplemented by renal transplantation with
      vigorous pre- and perioperative hemodialysis to deplete the body stores of
      oxalate. Although some authorities would reserve hepatic transplantation for
      patients in whom renal transplantation has failed, we suggest that combined liver
      and kidney transplantation is appropriate in patients who have never had a renal
      graft. Furthermore, the time has come to consider hepatic transplantation before
      any irreversible renal damage has occurred in these patients.

PMID- 1996584
TI  - Circulating interferon-alpha levels and hypertriglyceridemia in the acquired
      immunodeficiency syndrome.
AB  - PURPOSE: The metabolic disturbances seen during infection are thought to be due
      to cytokines, modulators of the immune response. The acquired immunodeficiency
      syndrome (AIDS) is characterized by a high prevalence of hypertriglyceridemia and
      at times depletion of body cell mass (wasting). Elevated circulating levels of
      cytokines have also been reported in AIDS. Therefore, we determined the
      relationship between circulating cytokine levels and lipid levels and between
      circulating cytokine levels and wasting in AIDS and human immunodeficiency virus
      (HIV) infection. PATIENTS AND METHODS: Serum samples from 45 patients with AIDS,
      13 subjects with evidence of HIV infection by presence of antibody but without
      AIDS (HIV positive), and 17 seronegative control subjects who had previously
      undergone body composition analysis were analyzed for triglyceride, cholesterol,
      interferon, tumor necrosis factor (TNF), and interleukin-1 levels. Eleven
      subjects with AIDS or HIV infection had sequential measurements. Interferon was
      analyzed by bioassay with identification using specific antibodies. TNF and
      interleukin-1 were assayed by enzyme-linked immunosorbent assay. Lean body mass
      was assessed by total body potassium. RESULTS: Serum interferon-alpha levels were
      significantly elevated in patients with AIDS (p less than 0.001 compared to
      controls), with detectable levels in 84% of AIDS patients. Interferon-alpha was
      not detectable in serum from controls, while three of 13 HIV-positive subjects
      had detectable interferon-alpha levels. There was a significant correlation
      between interferon-alpha levels and serum triglyceride levels in AIDS and HIV
      positive patients (R = 0.446, p less than 0.002). There was no relationship
      between interferon-alpha and serum cholesterol levels (R = -0.039, NS). In
      contrast only 11% of AIDS patients had detectable circulating TNF levels; the
      mean value for and the prevalence of detectable serum TNF levels were not
      significantly different from those of control subjects. Interleukin-1 was not
      detected in the circulation. There was no correlation between the presence of
      circulating TNF and serum triglycerides. There was no relationship between
      circulating interferon-alpha or TNF levels and the presence of wasting as
      measured by total body potassium. CONCLUSION: These studies suggest that
      interferon-alpha, which has previously been shown to modulate lipid metabolism in
      vivo and in vitro, may be responsible for the hypertriglyceridemia found in AIDS.

PMID- 1996586
TI  - Unsuspected mitral stenosis.
AB  - PURPOSE AND PATIENTS AND METHODS: We observed a series of patients in whom the
      diagnosis of mitral stenosis was first discovered in the echocardiography
      laboratory. Because of this experience, we examined the records of 152 patients
      with echocardiographic evidence of rheumatic mitral stenosis to determine the
      clinical characteristics and course of patients with unsuspected mitral stenosis
      as well as those factors that may have obscured the diagnosis. RESULTS: Of these
      152 patients, 18 had mitral stenosis that was unsuspected clinically until the
      echocardiogram. These patients were elderly, with a median age of 72 years. They
      were all referred for echocardiography because of cardiac symptoms. Eight
      patients were referred for evaluation of congestive heart failure. Five patients
      were referred for evaluation of aortic valve disease. Three patients were
      referred because of cerebrovascular accidents and atrial fibrillation. The
      Doppler-determined mean diastolic mitral gradient ranged from 4 to 15 mm Hg
      (mean: 7 mm Hg). Mitral stenosis ranged in severity from trivial to very severe.
      Eight patients had moderate to severe mitral stenosis with estimated mitral valve
      areas less than or equal to 1.5 cm2. Seven had mild or trivial mitral stenosis
      with estimated mitral valve areas greater than 1.5 cm2. After further evaluation,
      two patients underwent mitral valve surgery with improvement of congestive
      failure. In three patients, warfarin therapy was begun to prevent emboli. Thus,
      five of 18 patients had a significant immediate change in therapy because of the
      discovery of mitral stenosis. CONCLUSION: The diagnosis of mitral stenosis may
      not be suspected in the presence of advanced age, other serious cardiac and
      medical conditions, or mechanical factors that complicate the physical
      examination. In these patients, mitral stenosis may be hemodynamically
      significant and may cause significant symptoms.

PMID- 1996587
TI  - Prognostic significance of valvular regurgitation in patients with infective
      endocarditis.
AB  - PURPOSE: Doppler ultrasound is a sensitive modality for detecting and
      quantitating valvular regurgitation in patients with infective endocarditis.
      Because valvular regurgitation leads to heart failure, we evaluated the
      prognostic significance of Doppler-detected valvular regurgitation in patients
      with endocarditis who had not yet developed clinical heart failure. PATIENTS AND
      METHODS: We reviewed the medical records of 65 patients with a clinical diagnosis
      of infective endocarditis from May 1985 to March 1990. A total of 49 patients
      were included in the study: 33 patients with native valve endocarditis and 16
      patients with prosthetic valve endocarditis. The initial Doppler echocardiogram
      was examined in these patients to determine the presence and degree of valvular
      regurgitation. RESULTS: Significant (moderate to severe) valvular regurgitation
      was detected in 23 (47%) patients. The presence or absence of significant
      valvular regurgitation did not predict the development of congestive heart
      failure, the need for surgery, or death (p = NS). The development of congestive
      heart failure was significantly associated with the need for surgery (p less than
      0.0001) and death (p less than 0.05). CONCLUSION: We conclude that the detection
      of significant valvular regurgitation in patients with infective endocarditis who
      have not yet developed heart failure is not predictive of future complications
      nor does the absence of significant valvular regurgitation identify a group of
      patients with a more favorable prognosis. In our series, patients who developed
      congestive heart failure had a significantly higher incidence of surgery and
      death. Therefore, decisions regarding clinical management in patients with
      infective endocarditis should not be made solely on the presence or absence of
      echocardiographically detected valvular regurgitation.

PMID- 1996588
TI  - Comparison of labetalol versus enalapril as monotherapy in elderly patients with
      hypertension: results of 24-hour ambulatory blood pressure monitoring.
AB  - PURPOSE: This study compared the safety and efficacy of labetalol and enalapril
      as antihypertensive therapy for elderly patients. PATIENTS AND METHODS: A
      randomized, open-label, parallel controlled trial was conducted. After completing
      a 4-week placebo phase, 79 elderly (65 years or older) patients with an average
      standing diastolic blood pressure (BP) 95 mm Hg or above and 114 mm Hg or less
      were randomized to receive a 12-week course of either labetalol or enalapril in
      an open-label design. The patients' BP and heart rate were evaluated biweekly by
      trained observers unaware of the treatment status, and drug dosage was titrated
      (up to 400 mg twice a day of labetalol or 40 mg daily of enalapril) to achieve a
      standing diastolic BP of less than 90 mm Hg and a decrease of 10 mm Hg from
      baseline. Patients underwent 24-hour ambulatory BP monitoring (ABPM) at the end
      of the placebo phase and again after 8 weeks of active treatment. RESULTS: The
      treatment groups were comparable in their reduction of supine diastolic BP, with
      no significant differences between the two treatments. Labetalol demonstrated a
      significantly greater reduction (p less than 0.05) in standing diastolic BP at
      the end of the titration period compared to enalapril, but this difference was
      not significant by the end of the study period. Based on 24-hour ABPM readings,
      labetalol reduced mean 24-hour diastolic BP (p less than 0.05) and mean heart
      rate (p less than 0.05) more than enalapril. The labetalol-treated patients were
      significantly less often above their diastolic BP goal throughout the 24-hour
      ABPM period (p less than 0.01). The two treatments were equally well tolerated.
      CONCLUSIONS: The results indicate that labetalol and enalapril are equally
      effective in lowering supine diastolic BP in the elderly, but labetalol is more
      effective in lowering ambulatory BP and heart rate throughout the day.

PMID- 1996589
TI  - Results of bronchoscopically obtained lower airway cultures from adult sickle
      cell disease patients with the acute chest syndrome.
AB  - PURPOSE: The purpose of this study was to determine the frequency of bacterial
      pneumonia as a cause of the acute chest syndrome in adult patients with sickle
      cell disease based on bronchoscopically obtained lower airway cultures and to
      describe the clinical, laboratory, and roentgenographic features of the acute
      chest syndrome in a series composed entirely of adult patients with sickle cell
      disease. PATIENTS AND METHODS: We reviewed the hospital records from 19 episodes
      (18 patients) of acute chest syndrome in adult patients with sickle cell disease
      (greater than or equal to 19 years of age) who had undergone flexible
      bronchoscopy to obtain lower airway cultures between January 1979 and July 1987.
      We also recorded patients' clinical, laboratory, and roentgenographic
      characteristics. RESULTS: Pneumonia was diagnosed in four of 19 episodes (21%) of
      acute chest syndrome based on quantitative cultures obtained at bronchoscopy. The
      pneumonia was caused by Streptococcus pneumoniae in two patients and mixed
      aerobic and anaerobic organisms in the other two patients. Forty-four of 45 blood
      cultures were negative, and one grew Staphylococcus epidermidis, which was
      considered a contaminant. Chest roentgenograms revealed lower lobe involvement in
      17 episodes (90%) and bilateral infiltrates in six (32%). Pleural effusions
      occurred in seven episodes (37%), and pleural fluid samples obtained from five of
      these revealed sterile exudates. CONCLUSION: The results of this retrospective
      study suggest that bacterial pneumonia is an uncommon cause of acute chest
      syndrome in adult patients with sickle cell disease. These results are consistent
      with previous retrospective studies using noninvasive techniques to diagnose
      pneumonia. Nevertheless, there appeared to be no reliable noninvasive variables
      that could accurately differentiate between patients with and without pneumonia
      and, consequently, we recommend empiric antibiotic therapy in addition to usual
      supportive care of these patients.

PMID- 1996590
TI  - Idiopathic neutropenia: antineutrophil antibodies and clinical correlations.
AB  - PURPOSE: The present study was done to evaluate the clinical characteristics of a
      large series of adult patients with chronic idiopathic neutropenia, and correlate
      the presence of antineutrophil antibodies, their class (IgG or IgM), and their
      ability to fix complement with clinical parameters, including other
      hemocytopenias, splenomegaly, and infections. PATIENTS AND METHODS: One hundred
      twenty-one adult patients with chronic idiopathic neutropenia were studied. Serum
      neutrophil-binding antibodies were measured using paraformaldehyde-fixed
      granulocytes (PFGs) from normal volunteers as target cells. 125I-labeled
      staphylococcal protein A was used to detect IgG antibodies while IgM antibodies
      were detected by using 125I-labeled mouse monoclonal anti-IgM antibody. Sera
      containing antineutrophil antibodies were tested for their ability to fix
      complement on donor PFGs by using 125I-labeled monoclonal antibody to the third
      component of complement. RESULTS: Of the 121 patients with chronic idiopathic
      neutropenia, 71 patients had isolated neutropenia, while 50 had neutropenia
      combined with either anemia and/or thrombocytopenia. Among the 71 patients with
      isolated neutropenia, there were 51 females (72%), compared with 28 females (56%)
      among the 50 patients with combined hemocytopenias (p = 0.083). Patients with
      multiple hemocytopenias were significantly older (p less than 0.01), were more
      likely to demonstrate splenomegaly (p = 0.001), and may have had more infectious
      complications. From all the patients, 36% of sera were shown to have
      antineutrophil antibodies, with a non-significant trend for these to be found
      more frequently in patients with multiple hemocytopenias. Sera with mixed IgG-IgM
      antineutrophil antibodies were significantly more likely to fix complement than
      those with isolated IgG or IgM antibodies, and among the patients with
      antineutrophil antibodies, complement-fixing antibodies were significantly
      associated with multiple hemocytopenias. Splenomegaly was significantly
      associated both with antineutrophil antibodies (p = 0.008) and with infections (p
      = 0.007). Antineutrophil antibodies were not associated with infections.
      CONCLUSIONS: Approximately one third of adult patients with idiopathic
      neutropenia have IgG and/or IgM antineutrophil antibodies demonstrable in their
      serum. There is a subset of patients with idiopathic neutropenia with multiple
      hemocytopenias who tend to be older, less likely to show female predominance,
      more likely to have splenomegaly and infections, and more likely to have
      antineutrophil antibodies, especially mixed IgG-IgM and complement-fixing
      antibodies.

PMID- 1996591
TI  - Local reactions to radioiodine in the treatment of thyroid cancer.
AB  - PURPOSE: To compare the rate of local complications resulting from radioiodine
      ablation of thyroid cancer in patients with a residual intact thyroid lobe to
      that in patients who had more extensive surgical treatment prior to radioiodine
      administration. PATIENTS AND METHODS: We retrospectively studied 59 patients who
      had received 131I between 1979 and 1989. The patients were divided into two
      groups, depending on the extent of their previous surgical thyroid excision.
      Group 1 comprised 10 patients with a lobectomy or hemithyroidectomy before the
      ablative radioiodine dose, and Group 2 comprised 49 patients with more extensive
      thyroid excision (near-total or subtotal thyroidectomy) before the radioiodine
      treatment. RESULTS: Sixty percent of the 10 patients in Group 1 experienced some
      degree of neck pain or tenderness following radioiodine ablation of their
      residual thyroid. In one case, the local reaction was very severe and accompanied
      by the development of transient hyperthyroidism. There was only a 6% local
      complication rate in the patients who had undergone more extensive thyroid
      excision before ablative therapy (p less than 0.001), and none had a severe
      reaction. CONCLUSIONS: Patients with only unilateral surgical excision before
      radioiodine therapy have a higher rate of local complications than do patients
      treated with more extensive surgery prior to radioiodine ablation. If radioiodine
      is to be employed in such patients, they should be informed of this possible
      complication. Since evidence supports a dose effect in the pathogenesis of the
      complications, we recommend using a dose of less than 30 mCi for the initial
      ablation in these patients even though it may be necessary to repeat this dose to
      complete thyroid ablation.

PMID- 1996592
TI  - Efficacy of fludarabine, a new adenine nucleoside analogue, in patients with
      prolymphocytic leukemia and the prolymphocytoid variant of chronic lymphocytic
      leukemia.
AB  - PURPOSE: To describe the results of fludarabine therapy in patients with
      prolymphocytic leukemia (PLL) and the prolymphocytoid variant of chronic
      lymphocytic leukemia (CLL-Pro). PATIENTS AND METHODS: Seventeen patients with a
      diagnosis of PLL or CLL-Pro received fludarabine 30 mg/m2 over 30 minutes daily
      for 5 days every 4 weeks alone (12 patients), or with prednisone (five patients).
      Previously defined criteria for response were used. Differences in response rates
      according to various characteristics were evaluated by chi-square test. RESULTS:
      Three patients (18%) achieved complete remission, and three (18%) had a partial
      remission, for an overall response rate of 35%. Responses were durable and
      occurred in all involved organ sites. Lower response rates were observed in
      patients with anemia, thrombocytopenia, advanced Rai stages, and primary
      resistance to prior therapy. Toxicities were minimal except for febrile episodes
      associated with therapy. CONCLUSION: Fludarabine has shown encouraging results in
      these patients and deserves further investigation in combination with other
      active agents, and in the setting of front-line therapy.

PMID- 1996593
TI  - A two-step model for development of non-insulin-dependent diabetes.
AB  - Both insulin resistance and beta-cell dysfunction occur during the development of
      non-insulin-dependent diabetes mellitus (NIDDM), but controversy exists about
      which lesion is primary. Based on longitudinal studies in the Pima Indians, a
      population with the world's highest reported prevalence of NIDDM, a two-step
      model for development of the disease is proposed. The first step is transition
      from normal to impaired glucose tolerance, for which insulin resistance is the
      main determinant, and the second and later step is worsening from impaired
      glucose tolerance to diabetes, in which beta-cell dysfunction plays a critical
      role. This hypothesis is consistent with findings from other ethnic groups from
      many parts of the world.

PMID- 1996594
TI  - Elderly patients with congestive heart failure under prepaid care.
AB  - PURPOSE: Because of concern about the quality of care received by Medicare
      patients in health maintenance organizations (HMOs), the care of patients with
      congestive heart failure (CHF) in eight HMOs was compared with the care of fee
      for-service (FFS) Medicare cases. PATIENTS AND METHODS: We compared the care of
      170 patients with CHF enrolled in one of eight Medicare HMOs with the care of 191
      similar FFS patients. Panels of expert physicians developed criteria for
      evaluating quality of care, and specially trained nurse clinicians abstracted
      medical records. RESULTS: Outpatient evaluation and management were similar in
      both settings, although HMO patients were significantly more likely to be advised
      to restrict salt intake. However, FFS patients with uncontrolled hypertension
      were more likely to have their medication regimens changed (62% versus 36%, p
      less than 0.01). Ejection fractions were obtained equally as often, and inpatient
      management was similar for both groups. Nonetheless, HMO providers scheduled
      follow-up visits within 1 week of hospital discharge more often (42% versus 27%,
      p less than 0.01). CONCLUSIONS: This study suggests that financial incentives of
      prepaid care are not detrimental to most aspects of care for CHF patients. More
      rapid follow-up after hospital discharge for patients with CHF suggests that HMOs
      may be more effective in delivering continuity of care for patients with chronic
      illness.

PMID- 1996595
TI  - Two cases of adult T-cell leukemia associated with acute pancreatitis due to
      hypercalcemia.
AB  - We report two cases of adult T-cell leukemia associated with acute pancreatitis
      and hypercalcemia. After sudden onset of epigastralgia, acute pancreatitis and
      hypercalcemia were found in both patients. There were no diseases that could
      explain the acute pancreatitis except for hypercalcemia probably due to adult T
      cell leukemia. Thus we considered that hypercalcemia due to adult T-cell leukemia
      had led to acute pancreatitis. This is the first report of such a complication in
      adult T-cell leukemia.

PMID- 1996596
TI  - Artifactual elevation of thyroid-stimulating hormone.
AB  - A clinically euthyroid patient was found to have a normal serum thyroxine level
      and an elevated plasma thyrotropin (TSH) level measured by fluoroimmunoassay.
      Thyroid hormone therapy failed to suppress the TSH level. The TSH level was
      unresponsive to thyrotropin-releasing hormone (TRH) administration, alpha
      subunits of pituitary glycoproteins were undetectable in her plasma, and imaging
      of the pituitary-hypothalamic region was normal. Measurement of TSH with an assay
      containing sheep antibody to TSH failed to reveal TSH in the patient's plasma.
      Addition of mouse IgG to the TSH fluoroimmunoassay reduced the patient's TSH to
      an undetectable level. These observations are consistent with a spurious
      elevation of TSH due to the presence of an anti-mouse antibody. Artifactual
      elevations of TSH have not been identified commonly, but this possibility should
      be considered when the TSH level is inappropriate for the apparent state of
      thyroid function.

PMID- 1996597
TI  - Isolation of HTLV-I from muscle of a patient with polymyositis.

PMID- 1996598
TI  - Entamoeba histolytica infection and AIDS.

PMID- 1996599
TI  - Diclazuril for cryptosporidiosis in AIDS.

PMID- 1996600
TI  - Pulmonary hypertension in a patient with tryptophan-induced eosinophilia-myalgia
      syndrome.

PMID- 1996601
TI  - We think it's Lyme.

PMID- 1996602
TI  - Granulocytic sarcoma in myelodysplastic syndromes: clinical marker of disease
      acceleration.

PMID- 1996603
TI  - Fluconazole treatment without catheter removal in Candida albicans peritonitis
      complicating peritoneal dialysis.

PMID- 1996604
TI  - Contraindications to the use of ace inhibitors in patients with C1 esterase
      inhibitor deficiency.

PMID- 1996605
TI  - Diffuse alveolar hemorrhage in autologous bone marrow transplant recipients.

PMID- 1996606
TI  - Functional biology of intestinal goblet cells.
AB  - Goblet cells reside throughout the length of the small and large intestine and
      are responsible for the production and maintenance of the protective mucus
      blanket by synthesizing and secreting high-molecular-weight glycoproteins known
      as mucins. To elucidate the role of goblet cells in the biology of the intestinal
      tract, an overview of the physiological implications of the mucus gel is
      presented, including a concise review of the products secreted by the cell.
      Because of the unique nature of this highly polarized exocrine cell, the
      maturational reorganization of the cytoarchitecture and the cellular mechanisms
      by which goblet cells secrete their products are discussed. This includes
      elucidation of the baseline secretory pathway, which is dependent on the
      cytoskeleton for granule movement, and the accelerated secretory pathway, which
      is independent of the cytoskeleton but requires an extracellular signal to occur.
      Finally, the involvement of goblet cell mucins in the pathophysiology of
      intestinal neoplasia and ulcerative colitis are presented.

PMID- 1996607
TI  - Satellite cell activation in the stretch-enlarged anterior latissimus dorsi
      muscle of the adult quail.
AB  - Satellite cell activity was examined in the stretch-enlarge anterior latissimus
      dorsi muscle (ALD) of the adult quail. Thirty-seven birds had a weight equal to
      10% of their body mass attached to one wing while the contralateral wing served
      as an intra-animal control. At various time intervals after application of the
      wing weight (from 1 to 30 days), the birds were injected with tritiated thymidine
      and killed 1 h later. Stretched muscle length was greater by day 1 and mass by
      day 3 when compared with the contralateral muscle. Satellite cells actively
      synthesizing DNA were quantitated in fiber segments of the control and stretched
      ALD. A minimum of 1,500 muscle nuclei (satellite cell nuclei and myonuclei) were
      counted in each muscle. Labeling in stretched muscle was expressed by the percent
      labeled nuclei per total nuclei counted. Satellite cell labeling was initiated by
      day 1, peaked between days 3 and 7, and was not statistically different from
      control values at day 30. These results demonstrate that satellite cells are
      induced to enter the cell cycle in the stretch-enlarged ALD muscle from the adult
      quail, and the peak of proliferative activity is within the first week of
      stretch.

PMID- 1996608
TI  - Cadmium block of isometric contractions of isolated bullfrog atrial cells.
AB  - We studied the effect of cadmium, verapamil, and quinacrine on the force of
      contraction (Fp) of isolated, single, field-stimulated bullfrog atrial cells. All
      agents were applied or removed rapidly (t1/2 approximately 15 ms) to minimize
      intracellular concentration changes other than intracellular calcium
      concentration. Two components of twitch force were observed, one blocked by
      micromolar Cd2+ and the other by millimolar Cd2+. The two contributed about
      equally to the activation of the twitch. The "cadmium-sensitive" portion of force
      (that affected by [Cd] less than or equal to 100 microM) had a K1/2 approximately
      1 microM, was identical in magnitude to, and not additive with, a "verapamil
      sensitive" (10 microM) component of force, was most strongly affected by 50-ms
      pulses of Cd2+ when they were applied in the mechanical latent period, and was
      potentiated by catecholamines. The cadmium-insensitive portion of force was
      abolished by the removal of extracellular calcium and was greatly potentiated by
      quinacrine (3 or 10 microM), a blocker of Na-Ca exchange. The results are
      consistent with the idea that activating calcium enters the cell via both an
      inactivating cadmium-sensitive L-type channel and a noninactivating cadmium
      insensitive mechanism that is not Na-Ca exchange and leaves the cell via Na-Ca
      exchange.

PMID- 1996609
TI  - Mitochondrial biogenesis in striated muscles: rapid induction of citrate synthase
      mRNA by nerve stimulation.
AB  - Tonic contractile activity induces mitochondrial biogenesis in mammalian skeletal
      muscles, necessitating regulation of both nuclear and mitochondrial genes
      encoding mitochondrial proteins. In this study we compared the time course of
      induction of citrate synthase (CS) mRNA, a nuclear gene product, to that of genes
      encoded by mitochondrial DNA during the adaptive response to indirect nerve
      stimulation in tibialis anterior muscles of adult rabbits. A CS cDNA probe was
      prepared from a rabbit heart cDNA library by the polymerase chain reaction using
      synthetic oligonucleotide primers based on the published sequence of the porcine
      gene. This cDNA probe hybridized to a single band on Northern blots of total or
      polyadenylated RNA from adult rabbit tissues. Nerve stimulation for 3 days
      increased the abundance of CS mRNA relative to total cellular RNA by 2.3 +/- 0.2
      fold (mean +/- SE, n = 8; P less than 0.01). In contrast, CS enzyme activity and
      mitochondrial RNA transcripts were not significantly increased at this time
      point. However, when nerve stimulation was continued for 21 days, the increases
      in CS mRNA and mitochondrial RNAs were similar. These results support the
      hypothesis that genetic signaling mechanisms triggered by neural input are sensed
      initially within the nucleus and that expression of mitochondrial genes is
      regulated as a secondary event.

PMID- 1996610
TI  - Abnormalities in protein synthesis and degradation induced by extracellular pH in
      BC3H1 myocytes.
AB  - Metabolic acidosis impairs protein and amino acid metabolism in rat muscle. To
      examine how extracellular acidification affects cellular protein turnover, we
      studied the BC3H1 myocyte. At pH 7.1 vs. 7.4, intracellular pH was lower; the
      decrease was greater in cells incubated in N-2-hydroxyethylpiperazine-N'-2
      ethanesulfonic acid-tris(hydroxymethyl)aminomethane compared with bicarbonate
      buffer. We monitored degradation of proteins labeled with L-[14C]phenylalanine by
      measuring radioactivity released into media containing an excess of unlabeled
      phenylalanine. Extracellular acidification increased degradation compared with
      incubation at pH 7.4. Adding a physiological concentration of insulin (1 nM)
      decreased protein degradation at pH 7.1 and 7.4; a supraphysiological (71 nM)
      insulin concentration decreased degradation at pH 7.1 to the same rate as cells
      incubated at pH 7.4 without insulin. Compared with pH 7.4, protein synthesis
      decreased 29% at pH 7.2; at pH 7.6 it increased 129%. Insulin stimulated protein
      synthesis at all pHs, but at pH 7.4 the insulin-induced increase was less than
      the rate at pH 7.6 without insulin. Dexamethasone did not change protein
      breakdown regardless of the pH; it had variable effects on protein synthesis.
      Thus extracellular acidification causes marked changes in protein turnover in
      BC3H1 myocytes.

PMID- 1996611
TI  - Myofilament overlap in swimming carp. I. Myofilament lengths of red and white
      muscle.
AB  - To assess myofilament overlap during locomotion, we estimated the length of
      myosin and actin filaments in axial red and white muscle of carp. Myosin filament
      lengths were 1.52 +/- 0.009 and 1.50 +/- 0.037 micron (means +/- SD) in the red
      and white muscle, respectively, as measured from thin sections. After correction
      for shrinkage (using the troponin-based 385-A axial periodicity), thin filaments
      were 0.96 +/- 0.009 and 0.97 +/- 0.023 micron in the red and white muscles,
      respectively. Filaments were also isolated from the white muscle and negatively
      stained. Myosin filaments were 1.56 +/- 0.025 microns, and actin filaments were
      0.99 +/- 0.024 micron in length. The data from thin sections and isolated
      filaments agreed within 2% for actin and 4% for myosin filaments. The number of
      actin filament periods (24 for the red and white muscle) and the length of the
      filaments are the same as in frog. This suggests that the classic sarcomere
      length-tension curve of frog muscle may be used to estimate the functional
      properties of carp red and white muscle.

PMID- 1996612
TI  - Myofilament overlap in swimming carp. II. Sarcomere length changes during
      swimming.
AB  - This study was performed to determine myofilament overlap during swimming in
      carp. By using frozen sections, we found that sarcomere lengths of the red and
      white muscle could be related to the curvature of the backbone. Sarcomere length
      (SL) during swimming was calculated from an analysis of backbone curvature in
      high-speed motion pictures. Because carp have the same myofilament lengths as
      frogs, we related force generation to SL using the frog SL-tension curve. At slow
      swimming speeds, the red fibers are used at a SL of 1.91-2.22 microns, where
      force generation is calculated to be no less than 96% maximal. If the red fibers
      powered the escape response they would have to shorten to 1.45-1.55 microns,
      where force generation would be reduced to approximately 50% maximal and the
      fibers damaged. Instead, the white muscle fibers are recruited and because of
      their helical orientation (resulting in a higher gear ratio), they shorten to
      only 1.75 microns, where they generate no less than 85% maximal tension. Thus, by
      recruitment of fiber types with different orientations, the full range of
      movements is powered by fibers operating at nearly maximal overlap. This suggests
      that myofilament overlap is an important design constraint of muscular systems.

PMID- 1996613
TI  - Simultaneous measurement of intracellular pH and Ca2+ using the fluorescence of
      SNARF-1 and fura-2.
AB  - Upon cell stimulation with hormones and other mitogens, a variety of biochemical
      and physiological responses occur within the first few minutes. Changes in both
      intracellular pH (pHin) and intracellular Ca2+ concentration ([Ca2+]in) are
      prominent and play a major role in the signal transduction mechanism leading to
      the physiological response, i.e., secretion, neurotransmission, proliferation, or
      differentiation. However, it is not clear whether these ions work independently
      in the activation pathway leading to a particular physiological response. The
      fluorescence characteristics of most Ca2+ indicators are pH sensitive, and
      quantitative estimates of [Ca2+]in cannot be made without knowledge of pHin. Thus
      it is desirable to have a technique to simultaneously monitor these two ions with
      relatively high time resolution. Here we have developed experimental conditions
      that allow us to use optimum emission conditions for a pH fluorescent indicator
      SNARF-1 and optimum excitation conditions for the Ca2+ indicator fura-2. The
      fluorescence spectra of these compounds are sufficiently different to allow
      simultaneous measurement of pH and Ca2+ both in vitro and in situ. We have
      observed simultaneous changes in both pHin and [Ca2+]in in BALB/c 3T3 cells on
      treatment with the nonfluorescent Ca2+ ionophore 4-bromo-A23187. This temporal
      relationship between pHin and Ca2+ gives further credence to the
      interrelationship between these two second messengers in the expression of
      physiological responses.

PMID- 1996614
TI  - Cell fractionation and electron microscope studies of kidney folate-binding
      protein.
AB  - The subcellular distribution of folate-binding protein (FBP) and [3H]folate in
      the proximal tubule was examined using cell fractionation and different electron
      microscope (EM) techniques. Cell fractionation of rabbit proximal tubules
      revealed that FBP distributed into two modes: 50% of FBP distributed with
      alanylaminopeptidase activity (brush border), and the remaining FBP distributed
      with organelles of lower density that did not show a large digitonin-induced
      shift to greater density. Infusion of [3H]folate into the kidney followed by
      isolation and fractionation of the proximal tubules revealed a time-dependent
      shift of [3H]folate from the heavy (brush border) mode to the lighter organelle
      mode. By EM immunocytochemistry, rat kidney FBP locates in the brush border,
      endocytic invaginations, endocytic vacuoles, and dense apical tubules of proximal
      tubule cells. EM autoradiography of rat kidney 10 min after intravenous infusion
      of [3H]folate revealed that the label was significantly concentrated only in the
      brush border, endocytic vesicles, and lysosomes. These data support a mechanism
      of receptor-mediated endocytosis for the process of FBP-mediated folate transport
      in the kidney.

PMID- 1996616
TI  - Evaluation of the electroinjection method for introducing proteins into living
      cells.
AB  - The introduction of impermeant probes such as antibodies and other proteins into
      living cells without compromising physiological function is an important approach
      for studying cellular regulatory mechanisms. Many techniques including direct
      microinjection, liposome-mediated delivery, fusion of red cell ghosts, and
      osmotic lysis of pinocytic vesicles have been used to introduce proteins into
      intact cells. We have used a modification of the voltage-discharge technique to
      introduce antibodies and other proteins into living physiologically responsive
      pheochromocytoma and other cultured cells. In this technique, called
      electroinjection, a single discharge of relatively low field strength is used to
      transiently permeabilize the plasma membrane. Our experiments demonstrate that
      electroinjection permits the introduction of large amounts (microM) of probe into
      2-5 x 10(6) cells simultaneously without compromising cell viability or
      physiological responsiveness when performed under carefully defined conditions.
      They also demonstrate that electroinjection results in a single population of
      loaded cells and that protein incorporation is a function of field strength,
      capacitance, molecular weight of the protein, and the concentration of the
      protein in the electroinjection buffer. Interestingly, a significant fraction of
      the protein electroinjected into cells is trapped in the plasma membrane when
      cells are shocked at high capacitance. These results demonstrate that
      electroinjection appears to be an efficient method for loading exogenous proteins
      into cells while maintaining the integrity of the physiological properties of the
      cell.

PMID- 1996615
TI  - Na(+)-independent Cl(-)-HCO3- exchange in sarcolemmal vesicles from vascular
      smooth muscle.
AB  - Intracellular pH (pHin) affects vascular smooth muscle function, but the
      mechanisms that control pHin in this tissue are not well understood. These
      studies were performed to determine whether sarcolemmal vesicles from bovine
      superior mesenteric artery (SMA) contain a Na(+)-independent Cl(-)-HCO3-
      exchanger and, if so, to determine its sensitivity to membrane voltage and
      inhibitors. 36Cl- was taken up by vesicles into an osmotically active
      intravesicular space. In Na(+)-free media, an outwardly or inwardly directed HCO3
      gradient stimulated 36Cl- transport in the opposite direction. An outwardly
      directed unlabeled Cl- gradient stimulated 36Cl- uptake by a mechanism that was
      inhibited by external HCO3-. HCO3- or Cl- gradient-stimulated 36Cl- uptake was
      not due to voltage coupling between ions. In the nominal absence of HCO3-, a
      threefold outwardly directed OH- gradient did not affect 36Cl- uptake. Total 36Cl
      uptake was stimulated by an inside-positive voltage, but the HCO3- gradient
      stimulated component of 36Cl- uptake was insensitive to a change in membrane
      voltage. Finally, HCO3- gradient-stimulated 36Cl- uptake was inhibited by 4,4'
      diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) and furosemide, with 50%
      inhibitory concentration values equalling approximately 1.0 and 0.5 mM,
      respectively. These data indicate that sarcolemmal vesicles from bovine SMA
      contain a Na(+)-independent Cl(-)-HCO3- exchanger. This transport system is
      probably electroneutral and is inhibitable by DIDS and furosemide. A conductive
      pathway for Cl- is present in the vesicles, but Cl(-)-OH- exchange activity was
      not observed.

PMID- 1996617
TI  - Effect of cromakalim and lemakalim on slow waves and membrane currents in colonic
      smooth muscle.
AB  - The effects of cromakalim (BRL 34915) and its optical isomer lemakalim (BRL
      38227) were investigated in intact tissue and freshly dispersed circular muscle
      cells from canine proximal colon. Cromakalim and lemakalim hyperpolarized resting
      membrane potential, shortened the duration of slow waves by abolishing the
      plateau phase, and decreased the frequency of slow waves. Glyburide, a K channel
      blocker, prevented the effect of cromakalim on slow-wave activity. The mechanisms
      of these alterations in slow-wave activity were studied in isolated myocytes
      under voltage-clamp conditions. Cromakalim and lemakalim increased the magnitude
      of a time-independent outward K current, but cromakalim also reduced the peak
      outward K current. Glyburide inhibited lemakalim stimulation of the time
      independent background current. Nisoldipine also reduced the peak outward
      current, and in the presence of nisoldipine, cromakalim did not affect the peak
      outward component of current. This suggested that cromakalim may block a Ca
      dependent component of the outward current. Lemakalim did not affect the peak
      outward current. We tested whether the effects of cromakalim on outward current
      might be indirect due to an effect on inward Ca current. Cromakalim, but not
      lemakalim, was found to inhibit L-type Ca channels; however, glyburide did not
      alter cromakalim inhibition of inward Ca current. We conclude that the effects of
      cromakalim and lemakalim on membrane potential and slow waves in colonic smooth
      muscle appear to result primarily from stimulation of a time-independent
      background K conductance. The effects of these compounds on channel activity may
      explain the inhibitory effect of these compounds on contractile activity.

PMID- 1996618
TI  - Ovarian hydroxyeicosatetraenoic acids compared with prostanoids and steroids
      during ovulation in rats.
AB  - Hydroxyeicosatetraenoic acid methyl esters (HETEs) are lipoxygenase products of
      arachidonic acid that are generated along with prostaglandins (PGs) during acute
      inflammatory reactions. Whereas it is well known that ovarian PG levels increase
      during the ovulatory process, little is known about ovarian HETEs. This report
      compares the ovarian changes in 5-, 12-, and 15-HETE with ovarian PGE and PGF,
      along with progesterone, 17 alpha-hydroxyprogesterone, 4-androstene-3,17-dione,
      testosterone, and 17 beta-estradiol. Ovulation was induced in immature Wistar
      rats by sequential treatment with pregnant mare's serum gonadotropin and human
      chorionic gonadotropin (hCG). Follicles began rupturing 10 h after hCG treatment.
      The greatest correlation was among 12-HETE, 15-HETE, and progesterone, which
      increased to peak levels at 10 h after hCG. In contrast, the ovarian levels of 5
      HETE, 17 alpha-hydroxyprogesterone, testosterone, and 17 beta-estradiol all
      declined sharply beginning 4 h after hCG. 2 alpha,4 alpha,7-4,5-Epoxy-17-hydroxy
      4,17-dimethyl-3-oxo-androstane-2- carbonitrile (epostane), a potent inhibitor of
      steroid synthesis and ovulation, sharply reduced the synthesis of all five
      steroids within 30 min after its injection at 3 h after hCG. Among the five
      eicosanoids, epostane mainly inhibited 15-HETE. The results suggest that 15-HETE,
      along with progesterone, may have an important role in ovulation.

PMID- 1996619
TI  - Comparison of inhibitory actions of indomethacin and epostane on ovulation in
      rats.
AB  - Indomethacin, an inhibitor of cyclooxygenase that generates prostaglandins (PGs)
      from arachidonic acid, and 2 alpha,4 alpha,7-4,5-epoxy-17-hydroxy-4,17-dimethyl-3
      oxoandrostane- 2-carbonitrile (epostane), an inhibitor of 3 beta-hydroxysteroid
      dehydrogenase that generates progesterone from pregnenolone, are both potent
      inhibitors of ovulation. This report compares the dose-dependent effects of these
      two inhibitors on ovarian levels of 5-, 12-, and 15-hydroxyeicosatetraenoic acid
      methyl ester (HETEs), prostaglandin E2 (PGE), prostaglandin F2 alpha (PGF),
      progesterone, 17 alpha-hydroxyprogesterone, 17 beta-estradiol, 4-androstene-3,17
      dione, and testosterone during ovulation in 25-day-old immature Wistar rats. The
      ovulatory process was initiated by 10 IU of human chorionic gonadotropin (hCG).
      Indomethacin was given at 3 h after hCG in doses ranging from 0.0316 to 10.0
      mg/rat. A dose of 0.1 mg/rat was the lowest dose to significantly reduce the
      ovulation rate from the control level of 70.5 +/- 5.8 ova/rat. This dose also
      reduced 15-HETE, but not 5-HETE, 12-HETE, or the steroids. PGE and PGF were
      strongly inhibited by an even lower dose of indomethacin (0.0316 mg/rat), but
      this dose did not affect the ovulation rate. Epostane was given at 3 h after hCG
      in doses ranging from 0.1 to 5.0 mg/rat. A dose of 1.0 mg/rat was the lowest dose
      to significantly inhibit ovulation. This dose also reduced the ovarian levels of
      15-HETE and progesterone but not 5-HETE, 12-HETE, PGE, PGF, or the other
      steroids. The results indicate that the ovulation rate is most closely correlated
      to ovarian 15-HETE levels.

PMID- 1996620
TI  - Effect of iodine deficiency and cold exposure on thyroxine 5'-deiodinase activity
      in various rat tissues.
AB  - We measured thyroxine 5'-deiodinase I (T(4)5'D-I) activity in thyroid, liver, and
      kidney and thyroxine 5'-deiodinase II (T(4)5'D-II) activity in brown adipose
      tissue (BAT) in rats on a low-iodine diet (LID) to test the possibility that
      increased deiodinase activity in these tissues might contribute to the
      maintenance of ther serum 3,5,3'-triiodothyronine (T3) level. Control rats
      received LID plus KI. Experiments were also performed with LID and LID plus KI
      rats exposed to cold. T(4)5'D-I activity was greatly increased in the thyroids of
      LID rats but not in liver or kidney. We consider it likely that increased
      thyroxine (T4)-to-T3 conversion in the greatly enlarged thyroids of LID rats
      contributed to the maintenance of serum T3. T(4)5'D-II activity in BAT was
      markedly increased in LID rats and was further greatly increased on cold
      exposure. However, we were unable to demonstrate an increase in uncoupling
      protein mRNA levels in BAT in response to cold in LID rats. We attribute this to
      the very low serum T4 level, which limits substrate availability. This factor
      also makes it unlikely that BAT contributes to maintenance of serum T3 in LID
      rats.

PMID- 1996621
TI  - Gluco- and antimineralocorticoid effects on human sleep: a role of central
      corticosteroid receptors.
AB  - Cortisol modulates brain functions in humans. This principal endogenous
      glucocorticoid in humans decreases rapid-eye-movement (REM) sleep and increases
      slow-wave sleep (SWS). Because cortisol exerts its effect on brain functions via
      mineralocorticoid receptors (MR) and glucocorticoid receptors (GR), we were
      interested in which type of corticosteroid receptor mediates these steroid
      effects on sleep. Healthy men were tested in two double-blind experiments. In
      experiment I (n = 8), the subject's sleep was tested during four nights: 1) after
      pretreatment with dexamethasone (Dex, 4 mg/day) for 4 or 6 days and after
      additional infusion of placebo or cortisol (10 mg/h) during the experimental
      night, 2) after pretreatment with placebo for 4 or 6 days and after infusion of
      placebo or cortisol (10 mg/h) during the experimental night. In experiment II,
      subjects (n = 10) slept after intravenous administration of potassium canrenoate
      (200 mg, at 0800 and 1700 h before experimental nights) or placebo. Cortisol
      infusion moderately increased the percentage of SWS (P less than 0.05) and
      markedly decreased REM sleep (P less than 0.01); influence of cortisol on SWS did
      not depend on pretreatment with Dex. Dex reduced both SWS and REM sleep (P less
      than 0.05). Canrenoate markedly diminished SWS (P less than 0.01) but left REM
      sleep unaffected. The results suggest that corticosteroid-induced changes in SWS
      are mediated via MR-like central receptors in humans, whereas changes in REM
      sleep involve GR.

PMID- 1996623
TI  - Pathway and carbon sources for hepatic glycogen repletion in dogs.
AB  - The present studies were undertaken to quantitate the relative contributions of
      the indirect and direct pathways for hepatic glycogen repletion and to determine
      the role of splanchnic tissues in provision of C precursors used for the indirect
      pathway. For this purpose, we administered oral glucose (1.4 g/kg) enriched with
      [1-14C]glucose to 18-h fasted dogs and measured net hepatic and net
      gastrointestinal glucose, lactate, and alanine balance, hepatic and
      gastrointestinal fractional extraction [( 3H]lactate), release and uptake of
      lactate, as well as the total amount of hepatic glycogen formed from the oral
      glucose and the 14C labeling pattern of the glycogen-glucose C. Although net
      hepatic glucose uptake (8.7 +/- 0.6 g, 27% of the oral load) exceeded the amount
      of glycogen formed from the oral glucose (6.3 +/- 1.1 g), analysis of
      radioactivity in C-1 of the glycogen glucose indicated that nearly 50% of the
      glycogen was formed by the indirect pathway. Net hepatic uptake of lactate (1.4
      +/- 0.1 g) and alanine (1.5 +/- 0.1 g) could account for greater than 90% of
      glycogen formed by the indirect pathway if all of the lactate and alanine taken
      up by the liver had been incorporated into glycogen. Release of lactate and
      alanine by splanchnic tissues approximated the amount of lactate and alanine
      taken up by the liver. However, in addition to taking up lactate, the liver also
      produced nearly as much lactate as the gastrointestinal tract (1.8 +/- 0.2 vs.
      2.0 +/- 0.3 g, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1996622
TI  - Acute effect of L-carnitine on skeletal muscle force tests in dogs.
AB  - Using the mixed type musculus latissimus dorsi of the dog in the present work, we
      show the effect of carnitine on an in situ fatigue test. L-Carnitine appears to
      improve force of this muscle by 34% while stimulated in situ. This effect of
      carnitine is acute and (stereo)specific, since neither D-carnitine nor the
      structural analogue choline (also a tertiary amine) has a positive effect on
      contractile force. Because skeletal muscle is rich in carnitine and because
      carnitine transport is slow, its effect must be exerted outside the striated
      muscle cells. Insulin (with glucose) administration abolished the carnitine
      effect. It is speculated that facilitation of fatty acid oxidation in the blood
      vessel wall is the basis for this positive effect of carnitine.

PMID- 1996624
TI  - Evidence against important catecholamine compensation for absent glucagon
      counterregulation.
AB  - To assess the counterregulatory role of glucagon and to test the hypothesis that
      catecholamines can largely compensate for an impaired glucagon response, four
      studies were performed in seven normal volunteers. In all studies, insulin was
      infused subcutaneously (15 mU.m-2.min-1) and increased circulating insulin
      approximately twofold to levels (26 +/- 1 microU/ml) observed with intensive
      insulin therapy. In study 1, plasma glucose fluxes (D-[3-3H]glucose) and plasma
      substrate and counterregulatory hormone concentrations were simply monitored;
      plasma glucose decreased from 87 +/- 2 mg/dl and plateaued at 51 +/- 2 mg/dl for
      3 h. In study 2 [pituitary-adrenal-pancreatic (PAP) clamp], secretion of insulin
      and counterregulatory hormones (except for catecholamines) was prevented by
      somatostatin (0.5 mg/h i.v.) and metyrapone (0.5 g/4 h per os), and glucagon,
      cortisol, and growth hormone were reinfused to reproduce the concentrations of
      study 1. In study 3 (lack of glucagon response), the PAP clamp was performed with
      maintenance of plasma glucagon at basal levels, and glucose was infused whenever
      needed to reproduce plasma glucose concentration of study 2. Study 4 was
      identical to study 3, but exogenous glucose was not infused. The PAP clamp (study
      2) reproduced glucose concentrations and fluxes observed in study 1. In studies 3
      and 4, isolated lack of glucagon response did not affect glucose utilization but
      caused an early and persistent decrease in hepatic glucose production
      (approximately 60%) that caused plasma glucose to decrease to 38 +/- 2 mg/dl (P
      less than 0.01 vs. control 62 +/- 2 mg/dl), despite compensatory increases in
      plasma epinephrine. We conclude that, in a model of clinical hypoglycemia,
      glucagon's effect on hepatic glucose production is a dominant counterregulatory
      factor in humans and that its absence cannot be compensated for by increased
      epinephrine secretion.

PMID- 1996626
TI  - Influence of a mixed meal on splanchnic and interscapular energy expenditure in
      humans.
AB  - Pulmonary, splanchnic, and interscapular O2 uptake was studied in 14 male
      volunteers before and for 90 min after a mixed meal. Thermistor catheters were
      inserted into a hepatic vein, the azygous vein, the pulmonary artery, and the
      aorta. Systemic and regional blood flows were determined during indirect
      calorimetry measurements and recordings of blood temperature. After the meal,
      pulmonary O2 uptake rose by 33-49 ml/min and splanchnic O2 uptake increased by 16
      25 ml/min. In the azygous region O2 uptake did not increase significantly.
      Cardiac output increased after the meal by 1.1-1.5 l/min and splanchnic blood
      flow rose by 0.4-0.9 l/min. Azygous venous blood flow increased from 130 +/- 19
      ml/min to 163 +/- 23 ml/min. In relation to splanchnic O2 uptake, the blood
      drained splanchnic heat was low, 11 +/- 1 J/ml, and decreased to 7 +/- 1 J/ml
      after the meal. We conclude that after a mixed meal approximately one-half of the
      rise in O2 uptake occurs in the splanchnic organs; azygous-drained tissues,
      including possible interscapular brown adipose tissue, contribute minimally. The
      amount of heat drained with blood from the splanchnic region was low in relation
      to the splanchnic O2 uptake, indicating that splanchnic heat may be dissipated by
      routes other than the perfusing blood.

PMID- 1996625
TI  - IGF-I and the truncated analogue des-(1-3)IGF-I enhance growth in rats after gut
      resection.
AB  - Effects of insulin-like growth factor I (IGF-I) administration and that of the
      truncated analogue des-(1-3)IGF-I have been examined in 170-g rats over a 7-day
      period after surgery to remove 80% of the jejunum plus ileum. The doses
      administered via osmotic infusion pumps were 0.96 and 2.4 mg.kg-1.day-1 IGF-I and
      0.96 mg.kg-1.day-1 des-(1-3)IGF-I. All groups lost weight on the day after
      surgery, but over the next 3 days the des-(1-3)IGF-I and high-dose IGF-I groups
      stabilized better and subsequently gained significantly (P less than 0.05) more
      weight than the vehicle or low-dose IGF-I groups over the last 3 days. The weight
      gains (mean +/- SE) for the groups over this last 3-day period were 14.0 +/- 1.7,
      14.4 +/- 2.9, 21.9 +/- 1.7, and 20.8 +/- 1.0 g for the vehicle, low-dose IGF-I,
      high-dose IGF-I, and des-(1-3)IGF-I groups, respectively. The nitrogen balances
      over the last 3 days for the high-dose IGF-I and des-(1-3)IGF-I groups, at 242 +/
      14 and 217 +/- 13 mg/d, respectively, were significantly (P less than 0.05) more
      positive than the control group at 153 +/- 21 mg/d. These differences could at
      least partially be explained by changes in muscle protein breakdown, as assessed
      by 3-methyl-L-histidine excretion. The kidneys were heavier in all treatment
      groups and the thymus after administration of des-(1-3)IGF-I.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1996627
TI  - Plasma chromogranin A as a marker of sympathochromaffin activity in humans.
AB  - The extent to which the sympathochromaffin system compared with other
      endocrine/neuroendocrine tissues contributes to the plasma chromogranin A pool
      has not been defined. To test the hypothesis that the sympathochromaffin system
      is the major source of circulating chromogranin A only when that system is
      activated markedly, we measured chromogranin A concentrations in 200 human plasma
      samples known to have a broad range of norepinephrine and epinephrine
      concentrations, reflecting therefore a broad range of sympathochromaffin activity
      at the time of sampling. Plasma chromogranin A and norepinephrine concentrations
      were highly correlated when the sympathochromaffin system was activated markedly
      (cardiac arrest samples, n = 13, r = 0.8392, P less than 0.0005) and when there
      was release of large amounts of norepinephrine from tumors (pheochromocytoma
      samples, n = 17, r = 0.8132, P less than 0.001). However, when the
      sympathochromaffin system was activated less markedly, resulting in plasma
      catecholamine concentrations that spanned the physiological and lower
      pathophysiological range (nonpheochromocytoma noncardiac arrest samples, n =
      170), correlations between plasma chromogranin A and norepinephrine (r = 0.2877,
      P less than 0.0001) and epinephrine (r = 0.3814, P less than 0.0001) levels were
      relatively weak, although still statistically significant. Thus, at basal through
      moderate stress levels, norepinephrine and epinephrine concentrations accounted
      for only approximately 10-15% of the variance in plasma chromogranin A levels. We
      conclude that, although plasma chromogranin A concentrations are a valid marker
      of sympathochromaffin activity in humans, they are not a sensitive marker under
      physiological conditions.

PMID- 1996628
TI  - Effect of endurance training on sedentary energy expenditure measured in a
      respiratory chamber.
AB  - The effect of endurance training on 24-h energy expenditure (EE), basal metabolic
      rate (BMR), sleeping metabolic rate (SMR), and the thermic effect of food (TEF)
      was assessed in a respiratory chamber where only spontaneous physical activity
      (SPA) was allowed. Results from 20 highly trained male endurance athletes (25 +/-
      5 yr, 178 +/- 7 cm, 70 +/- 8 kg body wt, 64 +/- 7 kg fat-free mass) were compared
      with those of 43 untrained males who were matched for age (28 +/- 6 yr), height
      (175 +/- 5 cm), weight (73 +/- 13 kg), and fat-free mass (62 +/- 8 kg). Subjects
      were admitted to a metabolic ward, fed a weight-maintenance diet, and refrained
      from physical activity for at least 2 days before measurements. No significant
      differences were found with respect to 24-h EE (2,126 +/- 186 vs. 2,154 +/- 245
      kcal), BMR (1,808 +/- 342 vs. 1,709 +/- 329 kcal), SMR (1,523 +/- 120 vs. 1,555
      +/- 188 kcal), or TEF (24.9 +/- 9.2 vs. 21.3 +/- 6.7% of ingested calories; these
      values included the energy cost of arousal) between trained and untrained
      subjects, respectively, before or after adjusting for differences in body
      composition. Neither the 24-h respiratory quotient nor the level of SPA differed
      between the two groups. No relationship was found between maximal aerobic
      capacity and metabolic rate adjusted for differences in fat-free mass and fat
      mass. These results do not support an effect of fitness level on EE measured
      under sedentary conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1996629
TI  - Metabolic effects of IGF-I and insulin in spontaneously diabetic BB/w rats.
AB  - To examine the influence of insulin-dependent diabetes on the metabolic response
      to insulin-like growth factor I (IGF-I), awake chronically catheterized diabetic
      and nondiabetic BB/w rats received IGF-I (5 micrograms.kg-1.min-1) or insulin (2
      mU.kg-1.min-1) for 2 h while maintaining euglycemia. In nondiabetic rats, IGF-I
      and insulin produced similar twofold increases in glucose uptake, but insulin was
      more effective in reducing hepatic glucose production (90 +/- 15 vs. 5 +/- 11%; P
      less than 0.001) and beta-hydroxybutyrate levels (94 +/- 1 vs. 19 +/- 6%; P less
      than 0.001). In diabetic rats, insulin-stimulated glucose uptake was impaired
      (8.5 +/- 0.9 vs. 11.5 +/- 0.9 mg.kg-1.min-1 in nondiabetics; P less than 0.05).
      In contrast, IGF-I-stimulated glucose uptake was identical in diabetic and
      nondiabetic rats. Furthermore, IGF-I suppressed glucose production by 73% (P less
      than 0.01) and caused a greater lowering of beta-hydroxybutyrate levels (from 2.9
      +/- 0.8 to 0.8 +/- 0.3 mumol/l) in diabetic rats. We conclude that 1) the
      capacity of IGF-I infusion to stimulate glucose uptake is maintained in
      spontaneously diabetic BB rats that are insulin resistant, and 2) IGF-I infusion
      suppresses elevated glucose production rates and plasma ketone concentrations in
      diabetic rats but is relatively ineffective in nondiabetic rats. Thus the
      metabolic responses to infused IGF-I do not appear to be diminished in diabetic
      rats with impaired responses to insulin.

PMID- 1996630
TI  - Effect of a new mineralocorticoid antagonist mespirenone on aldosterone-induced
      hypertension.
AB  - The effects of the mineralocorticoid antagonist mespirenone on the development
      and maintenance of aldosterone-induced hypertension in Sprague-Dawley rats has
      been studied. Uninephrectomized saline-drinking male Sprague-Dawley rats were
      injected with either 0.2 ml olive oil, 50 g aldosterone, 1 mg mespirenone, 50 g
      aldosterone plus 500 g mespirenone, or 50 g aldosterone plus 1 mg mespirenone,
      each dissolved in 0.2 ml olive oil. Administration of aldosterone alone
      significantly increased the systolic blood pressure (SBP) from a control value of
      114 +/- 3.6 to 162 +/- 4 mmHg by the end of the 3-wk experimental period.
      Mespirenone given alone had no effect on SBP. However, mespirenone given in
      combination with aldosterone reversed the hypertension caused by aldosterone in a
      dose-dependent manner. Saline consumption and urinary output were slightly
      increased in aldosterone-treated rats compared with the other groups, but the
      body and organ weights were comparable in all groups. Microscopic examination of
      kidney and heart showed no abnormalities due to mespirenone. These results
      suggest that in vivo administration of mespirenone to Sprague-Dawley rats
      effectively prevents the aldosterone-induced hypertension.

PMID- 1996631
TI  - Functional and metabolic consequences of skeletal muscle remodeling in
      hypothyroidism.
AB  - Functional and metabolic responses of hypothyroid skeletal muscle were evaluated
      during steady-state isometric contraction conditions, using an isolated perfused
      rat hindlimb preparation. Treating rats with propylthiouracil (PTU) for 4-5 mo
      resulted in a 55% decrease (P less than 0.001) in citrate synthase activity in
      plantaris muscle and phenotypic remodeling of the plantaris, evident by a
      threefold increase in type I fiber area and a 13% decrease in type II fiber area.
      Perfusion of PTU (n = 9) and control (n = 9) rat hindlimbs of similar size, with
      similar inflow (approximately 10 ml/min) and oxygen content (approximately 20
      g/100 ml), resulted in similar oxygen deliveries to the contracting muscles (PTU
      11.4 +/- 0.58, control 9.54 +/- 0.75 mumol.min-1.g-1; P greater than 0.05). Ten
      minute tetanic contraction (100 ms at 100 Hz) periods at 4, 8, 15, 30, and 45
      tetani/min were elicited in consecutive ascending order. Oxygen consumption (VO2)
      was lower in the PTU group at all contraction frequencies (P less than 0.005),
      with a decrease in peak VO2 of 44% (PTU 3.01 +/- 0.29, control 5.35 +/- 0.42
      mumol.min-1.g-1; P less than 0.001). Oxygen extraction by the PTU muscle was only
      approximately 25% of that delivered. Developed tension was initially less (15%; P
      less than 0.05) in the PTU group but declined in a similar manner, as a percent
      of initial, to that of the control group. The slightly lower absolute tension
      development of the PTU muscle could not account for the large reduction in
      VO2.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1996632
TI  - Utilization of tyrosine dipeptides and acetyltyrosine in normal and uremic
      humans.
AB  - The impact of renal failure on the elimination and hydrolysis of three sources of
      tyrosine for parenteral nutrition, the dipeptides alanyltyrosine (Ala-Tyr),
      glycyltyrosine (Gly-Tyr), and N-acetyltyrosine (NAc-Tyr) was investigated in
      eight patients on regular hemodialysis therapy (HD) and seven healthy controls
      (CON). In CON, whole body clearance (Ctot) of Ala-Tyr (3,169 +/- 198 ml/min) was
      higher than Gly-Tyr (1,781 +/- 184, P less than 0.001), and both exceeded NAc-Tyr
      (284 +/- 24, P less than 0.001). In HD, Ctot of Ala-Tyr was not different from
      CON, but Ctot of Gly-Tyr (858 +/- 73, P less than 0.001) and NAc-Tyr (129 +/- 30,
      P less than 0.02) was decreased. The rise in plasma levels of constituent amino
      acids was higher in Ala-Tyr vs. Gly-Tyr (P less than 0.01). In HD, the pattern
      was similar, although the increase in Tyr was less than in CON. Plasma Tyr did
      not increase with NAc-Tyr in either group. Urinary loss of peptides was neglible,
      but 60% of NAc-Tyr infused was excreted by CON. The half-life of peptides
      incubated in CON and HD plasma was unchanged for Ala-Tyr (12.3 +/- 0.9 vs. 14.6
      +/- 1.9 min) and prolonged for Gly-Tyr in HD (101.7 +/- 4.9 vs. 131.3 +/- 12, P
      less than 0.05). Thus renal failure does not impair Ala-Tyr disposal and delays
      Gly-Tyr utilization. These differential effects on peptide assimilation
      underscore the importance of peptide structure on metabolism. Both peptides, but
      not NAc-Tyr, may serve as a nutritional substrate in renal failure patients.

PMID- 1996633
TI  - Description of a direct-indirect room-sized calorimeter.
AB  - A calorimeter suitable for measuring human energy expenditure has been assembled
      by the US Department of Agriculture in Beltsville, Maryland. The room-sized
      calorimeter is 3.05 X 2.74 X 2.44 m (20.39 m3). Direct and indirect calorimetry
      methods are used to simultaneously measure heat emission and energy expenditure.
      A water-cooled gradient layer chamber is used to measure human heat production
      directly. Indirect calorimetry is ascertained by measuring the changes in gas
      composition of the air entering and existing the chamber. The inlet and outlet
      air are each sampled three times every 100 s with a multiple gas analyzer to
      determine carbon dioxide and methane production and oxygen consumption within the
      chamber. A total of 30 measurements, which include temperature, pressure, gas
      fractions, flow rates, direct heat transfer, electrical power, and motion within
      the chamber, are converted from electrical to digital signals and recorded on
      magnetic disk nine times each minute. Real-time calculations for directly and
      indirectly measured energy expenditure are continuously updated and displayed.
      The performance of the calorimeter is assessed by the combustion of alcohol
      within the chamber. Results of these tests indicate that the direct heat recovery
      is 99.7 +/- 2.6 (SD) % and the indirect heat recovery is 100.3 +/- 1.3 (SD) %.

PMID- 1996634
TI  - Mechanism by which calcitonin gene-related peptide antagonizes insulin action in
      vivo.
AB  - Calcitonin gene-related peptide (CGRP) is a peptide with structural homology to
      amylin, which is present in nerve terminals of skeletal muscle and intestine. The
      effect of this peptide on in vivo insulin action was studied in conscious rats.
      All rats received 180 min euglycemic (5.6 mM) insulin (21.5 pmol.kg-1.min-1)
      clamp study in combination with [3-3H]- and [U-14C]glucose infusions. In the
      basal state, the plasma CGRP concentration was 36 +/- 5 pM, and the skeletal
      muscle CGRP concentration was 376 +/- 88 pmol/kg wet wt. CGRP was infused at 100
      pmol.kg-1.min-1 during the last 90 min of the insulin clamp study and determined
      a rise in plasma concentration to 781 +/- 34 pM. Hepatic glucose production was
      stimulated by the infusion of CGRP (35.6 +/- 6.1 vs. 24.4 +/- 4.4 mumol.kg-1.min
      1). During infusion in insulin alone, glucose uptake was 133.3 +/- 8.9 mumol.kg
      1.min-1 and decreased to 105.5 +/- 12.2 mumol.kg-1.min-1 with CGRP. However, the
      whole body rates of glycolysis (3H2O generation) were higher during the infusion
      of CGRP (83.9 +/- 6.1 mumol.kg-1.min-1) compared with insulin alone (72.2 +/- 7.8
      mumol.kg-1.min-1). By contrast, CGRP determined a severe impairment in muscle
      glycogen synthesis (11.7 +/- 3.9 vs. 47.8 +/- 5.0 mumol.kg-1.min-1). Skeletal
      muscle glucose 6-phosphate concentration was significantly increased after CGRP
      infusion compared with insulin alone (0.540 +/- 0.052 vs. 0.219 +/- 0.038 mumol/g
      wet wt; P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1996635
TI  - Role of leucine as a precursor of glutamine alpha-amino nitrogen in vivo in
      humans.
AB  - To assess the role of leucine as a precursor of glutamine alpha-amino N in vivo,
      five healthy men received primed continuous intravenous infusions of L
      [15N]leucine, L-[15N]alanine, and L-[2-15N]glutamine in the postabsorptive state
      on three separate days and over 7, 4, and 4 h, respectively. A steady state in
      isotopic enrichment was observed in every amino acid during the last hour of each
      isotope infusion and was used to calculate the rates of amino acid appearance
      (Ra) and interconversion. Leucine, alanine, and glutamine Ra values were 137 +/-
      18, 234 +/- 42, and 320 +/- 18 (SD) mumol.kg-1.h-1, respectively. Rates of N
      transfer from leucine to glutamine and alanine were 29 +/- 9 and 29 +/- 11
      mumol.kg-1.h-1, respectively; these rates represented 21 +/- 8 and 21 +/- 12%,
      respectively, of leucine's N and 9 +/- 3 and 13 +/- 4% of glutamine's alpha-amino
      N and alanine N, respectively. These results suggest that the endogenous branched
      chain amino acids released by protein breakdown are major precursors of both
      glutamine and alanine de novo synthesis in postabsorptive humans.

PMID- 1996636
TI  - Microdialysis studies of adipose tissue metabolism.

PMID- 1996637
TI  - Amino acid- and amine-induced gastrin release from isolated rat endocrine
      granules.
AB  - Secretory granules from rat antral tissue were isolated by differential
      centrifugation in sucrose and were confirmed as intact by electron microscopy.
      Gastrin release from the isolated granules was measured in response to
      stimulation with amino acids or their decarboxylated amine metabolites. Nine of
      13 amino acids tested were ineffective at inducing gastrin release, whereas all
      13 of the amine metabolites were potent stimulants of gastrin release. A pH
      gradient across the granule fraction membranes was estimated by acridine orange
      fluorescence and indicated an acidic interior. Changes in acridine orange
      fluorescence as an indicator of pH gradient dissipation showed that all of the
      amines, but only one of the amino acids, reversed acridine orange fluorescence.
      Ammonium chloride, similar to amines, both reversed acridine orange fluorescence
      and induced release of gastrin. It is concluded that amines 1) may directly
      stimulate gastrin granules to release their contents and 2) tend to alkalinize
      the gastrin granule interior. Some amino acids, in contrast, appear to directly
      stimulate gastrin release and do not affect the granule pH gradient.

PMID- 1996639
TI  - Saturation of hepatic transport of taurocholate in rats in vivo.
AB  - A single intravenous injection of [14C]taurocholate was followed up in blood and
      bile of rats submitted to steady intravenous infusions of taurocholate (TC) at
      rates of 0.0, 0.5, 1.0, and 1.5 mumol.min-1.100 g body wt-1 for at least 30 min.
      The transport rate constants and the amounts of TC in different compartments were
      estimated by weighted least-squares adjustment of a six-compartment model to the
      experimental data (3 compartments for TC distribution in blood, 2 compartments
      for liver, and 1 compartment for sinusoidal blood space). The saturation of the
      TC excretion rate was reached at 0.8 mumol.min-1.100 g body wt-1. It was
      characterized by a decrease of both the uptake and excretion rate constants, by
      an increase of the ratio of the amounts of TC in the two intrahepatic
      compartments (H'/H), and by an intrahepatic TC concentration of approximately 2
      mM. When tauroursodeoxycholate (TUDC) was infused at a rate of 0.5 mumol.min
      1.100 g body wt-1 together with TC at a rate of 1.5 mumol.min-1.100 g body wt-1,
      the TC excretion rate increased to 1.2 mumol.min-1.100 g body wt-1, and the
      excretion rate constant and H'/H decreased toward control values. These results
      support the hypothesis that the saturation of the transport of TC is due to TC
      hepatotoxicity and can be reduced by TUDC. Michaelis-Menten parameters, derived
      from saturation curves for both uptake and excretion steps, closely matched
      earlier results, thus confirming the good descriptive capacity of the model.

PMID- 1996638
TI  - Characterization of a gastrin-type receptor on rabbit gastric parietal cells
      using L365,260 and L364,718.
AB  - Previous studies have demonstrated that gastrin and the COOH-terminal octapeptide
      of cholecystokinin (CCK-8) stimulated in vitro acid secretion from isolated
      rabbit gastric parietal cells. Both peptides bind to receptor sites located on
      these cells and induce an increase in phosphoinositide turnover and an uptake of
      [14C]aminopyrine ([14C]AP) with the same efficacy and potency. In the present
      study, we used the 3-(benzoylamino)-benzodiazepine analogue L365,260 and the 3
      (acylamino)-benzodiazepine analogue L364,718 to investigate what type of receptor
      (gastrin type or CCK-A type) is involved in the regulation of the H+ secretory
      activity of the rabbit parietal cell. Neither L365,260 nor L364,718 alone caused
      stimulation of [3H]inositol phosphates ([3H]InsP) production. Each analogue
      inhibited 125I-labeled gastrin or 125I-CCK-8 binding to parietal cells and
      gastrin- or CCK-8-induced [3H]InsP production and [14C]AP accumulation. In all
      cases, L365,260 was approximately 70-100 times more potent than L364,718 (IC50
      approximately 2-4 nM for L365,260 and approximately 0.2-0.4 microM for L364,718).
      Nevertheless, each antagonist displayed the same potency to inhibit the effects
      of gastrin or CCK-8. These results demonstrate that gastrin and CCK-8 interact
      with the same "gastrin-type" receptor on parietal cells. Moreover, L365,260
      behaves as a competitive antagonist of the action of gastrin on parietal cells.
      Gastrin induces a rise in the levels of inositol 1,4,5-trisphosphate
      [Ins(1,4,5)P3] and inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P4] within the
      first seconds after parietal cell stimulation. The fact that L365,260 (10 nM)
      totally suppressed the gastrin-induced formation of Ins(1,4,5)P3 and
      Ins(1,3,4,5)P4 suggests the involvement of these isomers in the mediation of acid
      secretion through gastrin receptor activation.

PMID- 1996640
TI  - Role of CCK in regulation of pancreaticobiliary functions and GI motility in
      humans: effects of loxiglumide.
AB  - To evaluate the physiological role of cholecystokinin (CCK) in humans, we studied
      the influence of the specific CCK receptor antagonist loxiglumide (CR 1505) on
      gallbladder contraction, pancreatic enzyme output, plasma CCK concentrations,
      mouth-to-cecum transit time (MCTT), stool weight, and fecal fat excretion.
      Infusion of CCK-8, producing CCK plasma levels of 10-12 pmol/l, decreased
      gallbladder volume to 21% of the initial volume (P less than 0.01) and increased
      bilirubin output 8- to 10-fold and pancreatic enzyme secretion 2- to 4-fold.
      Infusion of loxiglumide (10 mg.kg-1.h-1 iv) abolished CCK-8-stimulated enzyme and
      bilirubin output. Basal gallbladder volume increased 68% during loxiglumide
      infusion (P less than 0.001) and 137% (P less than 0.001) after 7 days of oral
      loxiglumide treatment (3 x 1.6 g/day). Gallbladder contraction and bilirubin
      output in response to the intraduodenal instillation of a liquid meal (382 kcal)
      was completely inhibited by loxiglumide; gallbladder volume even increased 45%
      postprandially during loxiglumide infusion (P less than 0.02) and 145% after long
      term loxiglumide treatment (P less than 0.001). Meal-stimulated pancreatic enzyme
      output was diminished 46-53% after acute and 25-29% after chronic administration
      of loxiglumide. Meal-stimulated integrated plasma CCK-immunoreactive (CCK-ir)
      concentrations, determined by RIA, were 3.2-fold higher during loxiglumide
      infusion (P less than 0.02); plateau CCK levels were markedly elevated (10.1 +/-
      1.4 vs. 3.7 +/- 0.5 pM). Plasma CCK-like bioactivity, measured by a sensitive
      bioassay, was identical to CCK-ir levels in the absence of loxiglumide; in the
      presence of loxiglumide, no circulating CCK-like bioactivity was detectable,
      indicating complete inhibition of plasma CCK. MCTT was augmented 24% (P less than
      0.05). Oral treatment with loxiglumide increased stool weight 72% (P less than
      0.01) and fecal fat excretion 186% (P less than 0.001). In conclusion, 1) meal
      induced gallbladder contraction and fasting tone are primarily controlled by CCK;
      2) the contribution of CCK to the intestinal phase of postprandial pancreatic
      enzyme secretion is 40-50%; 3) GI motility and absorption are partially
      controlled by CCK; and 4) postprandial CCK secretion is substantially augmented
      by loxiglumide via an unknown mechanism.

PMID- 1996641
TI  - Vitamin D-regulated calcium transport in Caco-2 cells: unique in vitro model.
AB  - The human colon adenocarcinoma cell line Caco-2 is the only intestinal cell line
      to differentiate spontaneously in culture exhibiting structural and biochemical
      characteristics of mature enterocytes and to possess a vitamin D receptor in the
      fully differentiated state. Transepithelial calcium transport was characterized
      in differentiated Caco-2 cells grown on permeable filters supports to assess the
      potential utility of this cell line as an in vitro model to study 1,25
      dihydroxyvitamin D3 [1,25(OH)2D3]-induced calcium transport. Calcium transport
      was increased in a dose-dependent manner by 1,25(OH)2D3. Total calcium transport
      at different calcium concentrations could be fitted to a modified Michaelis
      Menten equation containing a linear transport component. The maximum rate of
      saturable calcium transport was increased by 4.3-fold (P less than 0.005) in
      cells treated with 10(-8) M 1,25(OH)2D3. This treatment also increased the
      apparent buffer calcium concentration that results in half-maximal velocity from
      0.4 to 1.3 mM but had no significant effect on nonsaturable calcium transport.
      Caco-2 cells grown on permeable filter supports provide a unique in vitro human
      cell culture model to study the mechanism of vitamin D-regulated transepithelial
      intestinal calcium transport.

PMID- 1996642
TI  - Role of kallikrein-kinin system in pathogenesis of bacterial cell wall-induced
      inflammation.
AB  - The plasma kallikrein-kinin system is activated in Gram-negative sepsis and
      typhoid fever, two diseases in which bacterial products have been shown to
      initiate inflammation. Because a single intraperitoneal injection of bacterial
      cell wall peptidoglycan-polysaccharide polymers from group A steptococci (PG-APS)
      into a Lewis rat produces a syndrome of relapsing polyarthritis and anemia, we
      investigated changes in the role of the kallikrein-kinin system in this model of
      inflammation. Coagulation studies after injection of PG-APS revealed an immediate
      and persistent decrease in prekallikrein levels. High-molecular-weight kininogen
      levels decreased significantly during the acute phase and correlated with the
      severity of arthritis. Factor XI levels were decreased only during the acute
      phase. Antithrombin III levels remained unchanged, indicating that neither
      decreased hepatic synthesis nor disseminated intravascular coagulation caused the
      decreased plasma contact factors. Plasma T-kininogen (an acute phase protein) was
      significantly elevated during the chronic phase. PG-APS failed to activate the
      contact system in vitro. Thus the kallikrein-kinin system plays an important role
      in this experimental model of inflammation, suggesting that activation of this
      system may play a role in the pathogenesis of inflammatory bowel disease and
      rheumatoid arthritis in which bacterial products might be etiologically
      important.

PMID- 1996643
TI  - Ion transport across isolated pig jejunum.
AB  - Sodium, chloride, and glucose transport were studied in stripped pig jejunal
      epithelium mounted between halfchambers. The epithelium proved to be stable for
      experimental purposes for up to 2 h. Net sodium absorption was electrogenic and
      was dependent solely on sodium-glucose cotransport. Both sodium and glucose
      influx varied with mucosal glucose concentration; when fitted to the Michaelis
      Menten equation the two fluxes generated glucose-dependent Michaelis constant
      values of 1.5 and 9.6 mM, respectively. In the absence of mucosal glucose, the
      flux ratios for sodium and chloride were of unity, and the unidirectional fluxes
      were linearly dependent on the ion concentrations. The chloride accompanying
      sodium in open circuit was driven by the potential generated by the sodium
      glucose absorption (-5 mV) and supported an absorption of 1 mumol.cm-2.h-1 NaCl.
      Substituting 2-hydroxyethanesulfonate for chloride decreased total tissue
      conductance and reduced the sodium fluxes. This effect cannot be ascribed to
      sodium-chloride cotransport but reflects the different mobilities of the ion
      pairs in solution. Chloride secretion can be induced by theophylline.

PMID- 1996644
TI  - Intestinal motility changes in rats after enteric serotonergic neuron
      destruction.
AB  - The myenteric plexus consists of several subpopulations of morphologically and
      chemically distinct neurons known to contain a variety of peptides and amines,
      one of which is serotonin (5-hydroxytryptamine). These neurons are considered
      essential for nerve-to-nerve transmission. In the present study, we investigated
      the effect of 5,6- and 5,7-dihydroxytryptamine (5,6-DHT; 5,7-DHT), indoleamine
      neurotoxins that selectively and irreversibly injure the serotonergic neurons of
      the myenteric plexus. Treatment with 5,6-, or 5,7-DHT caused marked disruption of
      the activity front of the migrating myoelectric complex (MMC), increased its
      duration, and decreased its propagation velocity. At higher doses, 5,7-DHT also
      reduced the slow-wave frequency. Immunohistochemical techniques showed that
      tissue from rats treated with 5,7-DHT was depleted of serotonin-like
      immunoreactivity within the myenteric plexus neurons. Reserpine also caused
      motility and immunohistochemical changes similar to those induced by the two
      neurotoxins. Therefore, destruction of enteric serotonergic neurons disrupts the
      MMC. These studies support the cellular concepts that serotonergic neurons
      function as interneurons in the myenteric plexus, modulating and processing the
      neural stimuli, and that serotonin is an important neurotransmitter in the small
      intestine.

PMID- 1996645
TI  - Effect of two new cholecystokinin antagonists on gallbladder emptying in
      opossums.
AB  - In this investigation we evaluated the effect of two new cholecystokinin (CCK)
      antagonists, CR 1409 and L364,718, on gallbladder emptying in the opossum.
      Gallbladder emptying was elicited by both exogenous and endogenous CCK. The three
      test challenges were 1) intravenous infusion of CCK octapeptide (OP) (10 ng.kg
      1.min-1), 2) feeding, and 3) intraduodenal infusion of Isocal (0.4 ml/min), a fat
      containing nutrient. During control conditions each test challenge elicited
      approximately 60% gallbladder emptying within 30 min and 70% emptying by 60 min.
      At given doses both CR 1409 and L364,718 substantially antagonized or abolished
      the gallbladder emptying elicited by each of the test challenges. The antagonism
      for postprandial gallbladder emptying was diminished between 30 and 50 min
      compared with that for CCK-OP infusion and intraduodenal infusion of Isocal.
      Unexpectedly, the gallbladder emptying induced by infusion of motilin (5
      micrograms.kg-1.h-1) was antagonized by either CR 1409 or L364,718. In
      anesthetized animals, gallbladder contraction was induced by a variety of
      agonists, such as bethanechol, histamine phosphate, 5-hydroxytryptamine, and
      phenylephrine. In this later model CR 1409 and L364,718 functioned solely as
      selective antagonists. We conclude that for the opossum gallbladder 1) the CCK
      antagonists CR 1409 and L364,718 antagonize or abolish gallbladder emptying
      induced by exogenous or endogenous CCK; 2) the pattern of CCK antagonism after
      feeding suggests that the early phase of postprandial gallbladder emptying is
      mediated by a mechanism other than endogenous CCK, whereas late postprandial
      emptying is mediated by release of endogenous CCK; and 3) CR 1409 and L364,718
      are not totally specific antagonists for gallbladder CCK receptors alone but also
      antagonize gallbladder contraction induced by motilin.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1996646
TI  - Sucrase-alpha-dextrinase in diabetic BioBreed rats: reversible alteration of
      subunit structure.
AB  - BioBreed (BB) Wistar rats develop diabetes mellitus, which closely resembles the
      human disease, in 50% of progeny. Intestinal sucrase-alpha-dextrinase, a
      glycoprotein hydrolase of the enterocyte's brush border consisting of 140-kDa
      alpha-dextrinase and 125-kDa sucrase subunits, is essential for surface digestion
      of carbohydrate nutrients. Although its catalytic characteristics were found to
      be maintained in the diabetic state, the structure of the subunits, as compared
      with normal Wistar rats, was altered in the BB rat within 2 days of the onset of
      diabetes. Its capacity to react in a solid-phase immunoassay was reduced by 50%;
      when examined by 6% acrylamide electrophoresis, the sucrase subunit was increased
      in mass by 5 kDa and, in some BB rats, the dextrinase subunit was reduced by 5
      kDa. Intact rats labeled intraintestinally with [35S]methionine displayed the
      alteration within 6 h of synthesis, indicating that nonenzymatic glycosylation
      could not account for the structural change. This mass change was not seen in
      streptozotocin-induced diabetes and was independent of the plasma glucose
      concentration or the degree of acidosis. Deglycosylation with peptide N
      glycosidase indicated that the N-linked chains of the normal dextrinase subunit
      (11 kDa) have twice the mass of those in the BB rat (6 kDa) and that the sucrase
      subunit may have an increased mass of O-linked chains. Overall, these experiments
      point to changes in glycosylation as a mechanism of structural alteration in
      congenital diabetes. Despite persistence of the insulin-dependent diabetes, the
      subunit pattern eventually became indistinguishable from normal, but at
      differential rates (21 days and 35 days, respectively, for sucrase and dextrinase
      subunits).

PMID- 1996647
TI  - Canine ileocolonic sphincter: flow, transit, and motility before and after
      sphincterotomy.
AB  - Our hypothesis was that the canine ileocolonic sphincter (ICS), per se, would
      have little regulatory effect on the transit of chyme from ileum to colon. We
      argued, from earlier observations, that the ileocolonic junction was influenced
      more by functional motor integration of the ileum, ICS, and proximal colon. In
      five dogs, the ileocolonic sphincter was ablated by extramucosal sphincterotomy;
      the operation significantly lowered tonic pressures at the ICS. Animals were then
      studied in the fasting state and postprandially. Ileal flow was estimated by
      marker dilution, and ileocolonic flow was estimated by total recovery of chyme
      from a colonic cannula. Transit times were measured after the bolus infusion of
      nonabsorbable markers. Ileocolonic sphincterotomy did not significantly alter
      flow rates or transit times of chyme across the ICS, although ileal motor
      patterns were changed after sphincterotomy. We concluded that the ICS probably
      has only a small effect on transit and flow at the ileocolonic junction. These
      findings argue for the importance of integrated motility of the ileum, ICS, and
      proximal colon in controlling the flow of chyme in this region.

PMID- 1996648
TI  - Intracellular recordings from gallbladder ganglia of opossums.
AB  - Postganglionic parasympathetic neurons of the opossum gallbladder were studied
      using morphological and intracellular electrophysiological recording techniques.
      On average there were 17 ganglia/cm2 with 8 neurons/ganglion arranged as loosely
      or densely packed clusters. Intracellular injection of horseradish peroxidase
      identified two types of neurons. Most of the neurons (approximately 80%) had a
      single long process that extended beyond the ganglion border with few or no short
      additional neurites. The other type was multipolar, having several processes that
      did not appear to extend beyond the ganglion border. Gallbladder neurons had
      passive and active electrical properties similar to other parasympathetic
      ganglion cells. Most of neurons studied (71%) responded to intracellular
      injection of suprathreshold depolarizing current with a short burst of action
      potentials. The remaining neurons (29%) responded with only an initial action
      potential. Seventy percent of the neurons tested received nicotinic fast
      excitatory postsynaptic potentials (EPSPs). Nineteen percent of these neurons
      also exhibited a slow depolarizing response following repetitive orthodromic
      nerve stimulation. Cholecystokinin octapeptide sulfate (CCK-8, 0.1-500 nM) had no
      effect on resting membrane potential or membrane input resistance. However, CCK-8
      increased the amplitude of fast EPSPs evoked by orthodromic nerve stimulation by
      facilitating release of acetylcholine because CCK-8 had no effect on the
      postsynaptic response to exogenously applied acetylcholine. These data suggest
      that the ganglionated plexus of the gallbladder may mediate some of the observed
      effects of CCK-8 on gallbladder motility.

PMID- 1996649
TI  - Effects of CCK receptor blockade on intestinal motor activity in conscious dogs.
AB  - This study employed a cholecystokinin (CCK) antagonist to evaluate whether
      endogenous CCK regulates fasted and fed motor patterns of the small intestine.
      Experiments were performed in six conscious dogs, each in duplicate. Motor
      activity was recorded by six strain-gauge transducers implanted along the small
      intestine. The effects of the CCK analogue caerulein and the CCK antagonist
      loxiglumide were studied in fasted and fed states. Computer analysis determined
      contractile frequency and area under contractions. Caerulein given as an
      intravenous bolus 30 min after phase III dose dependently caused a burst of
      phasic contractions preceded by a retrograde giant contraction. Continuous
      intravenous infusion of 10 mg.kg-1.h-1 loxiglumide completely abolished the
      effects of 10 ng/kg caerulein, which increases plasma CCK immunoreactivity to
      postprandial levels. Loxiglumide, at 10 mg.kg-1.h-1, markedly reduced the
      increase in phasic contractions due to a supraphysiological dose of 50 ng/kg
      caerulein to 14 +/- 6(SD)% of the control without loxiglumide (P less than 0.01).
      The motor activity stimulated by the cholinesterase inhibitor neostigmine (10
      micrograms/kg) was not altered by loxiglumide. Loxiglumide given in the fasted
      state decreased contractile frequency from 9.5 +/- 0.7 to 8.1 +/- 0.6/min and
      reduced the area under contractions during phase II to 81 +/- 5% of the control
      without loxiglumide (P less than 0.05). Loxiglumide also decreased contractile
      frequency during the fed state from 9.7 +/- 0.6 to 8.3 +/- 0.5/min and reduced
      the area under contractions to 78 +/- 6% of the control without loxiglumide (P
      less than 0.05). Thus loxiglumide acts as a specific antagonist of the actions of
      CCK on small intestinal motor activity in the dog. Loxiglumide, at a dose that
      abolishes actions of endogenous CCK, significantly decreased fasting motor
      activity during phase II. Loxiglumide also significantly reduced motor responses
      to feeding but did not prevent interruption of migrating motor complex cycle by a
      meal. CCK plays a physiological role in regulation of fasting and fed motor
      activity of small intestine, although other factors in addition to CCK mediate
      meal-induced motor activity.

PMID- 1996650
TI  - Index of contractility: quantitative analysis of hepatic venous distensibility.
AB  - The low-pressure resistance vessels of the splanchnic circulation are passively
      distensible, and changes in regional blood pressures can lead to large changes in
      vascular resistance. The relationship between distending blood pressure (Pd) and
      vascular resistance (R) is described as a constant, the index of contractility
      (IC) where IC = R x Pd3. IC was derived in an isolated blood-perfused liver and
      was confirmed in vivo for both pre- and postsinusoidal resistance sites. IC does
      not change passively in response to wide changes in blood flow or hepatic outflow
      pressure. IC is dramatically altered in response to active vasoconstriction. In
      vivo, the presinusoidal IC rose from a control level of 12.2 +/- 4.2 to 92.7 +/-
      20.6 IC units (mmHg4.ml-1.min.kg body wt) in response to 1.25 micrograms.kg-1.min
      1 norepinephrine intraportal; the postsinusoidal IC rose from 20.4 +/- 2.3 to
      59.6 +/- 14.2 IC units. IC reflects resistance changes secondary to active
      contractile responses independent of the passive consequences of the distensible
      nature of the resistance sites. We suggest that these concepts can be applied to
      any vascular bed with distensible resistance vessels.

PMID- 1996651
TI  - Effect of sustained mesenteric nerve stimulation on intestinal oxygenation in
      developing swine.
AB  - The effects of sustained mesenteric nerve stimulation on intestinal oxygenation
      were determined in 3- and 35-day-old swine. Studies were conducted in
      pentobarbital-anesthetized animals during free-flow or constant-flow perfusion.
      Square-wave stimuli sufficient to induce maximal resistance vessel constriction
      were applied to postganglionic periarterial mesenteric nerves and each
      stimulation was sustained until measured variables reached steady state. When
      vascular resistance data were analyzed without data transformation,
      autoregulatory escape of intestinal vascular resistance was more complete in 3-
      than in 35-day-old animals when the escape process was complete; however,
      expression of these data as escape indexes revealed a similar degree of escape in
      both age groups. In 35-day-old animals, (a-v)O2 increased during sustained nerve
      stimulation under free-flow conditions; under constant-flow conditions, (a-v)O2,
      86Rb extraction, and capillary permeability-surface area product were lower at
      completion of the escape process compared with baseline. In 3-day-old swine,
      these variables remained unchanged from baseline. Intestinal O2 uptake was
      compromised by sustained nerve stimulation, and this effect was similar in both
      age groups. We conclude that sustained nerve stimulation reduces intestinal
      oxygenation to a similar degree in 3- and 35-day-old swine. It is important to
      note, however, that the response of 3-day-old swine may be dissimilar from that
      which occurs during immediate postnatal life; indeed, the intestinal hemodynamic
      response of swine less than or equal to 1 day old should not be extrapolated from
      the response of 3-day-old animals.

PMID- 1996652
TI  - Microcirculatory changes in sodium taurocholate-induced pancreatitis in rats.
AB  - Using an in vivo microscopy technique, we studied the microcirculatory changes in
      sodium taurocholate-induced pancreatitis in rats. With a computerized image
      analyzer system, blood flow, vascular permeability changes, and capillary
      densities were measured. Intraductal infusion of 0.4 ml saline had only minor
      effects on the microcirculation. Various concentrations and volumes of sodium
      taurocholate solutions were infused into the pancreatic duct. Sodium taurocholate
      (0.4 ml, 4%) led to increased vascular permeability preceding stasis within 232
      +/- 47 s, followed by hemorrhagic necrosis in the head of the pancreas. In the
      corpus close to the tail of the pancreas capillary blood flow was maintained. In
      conclusion, this study shows that the microcirculation of the pancreas can be
      excellently investigated with in vivo microscopy. With this method, tremendous
      distribution disturbances of the microcirculation in the pancreas can be seen in
      the course of acute pancreatitis. Vascular permeability changes and stasis of the
      microcirculation represent the primary microcirculatory events in acute
      pancreatitis induced by sodium taurocholate in the areas where hemorrhagic
      necrosis occurs.

PMID- 1996653
TI  - Ambulatory monitoring of human colonic motility.

PMID- 1996654
TI  - Development of type II pneumocytes in rat lung.
AB  - At a late stage of fetal development, the mammalian alveolar epithelium undergoes
      an abrupt differentiation as a part of the preparation of the lung for the
      postnatal demands of gas exchange. Some of the most striking changes occur in the
      type II pneumocytes as they lose their glycogen and start to produce the
      lamellated inclusion granules that contain pulmonary surfactant. Premature birth
      before adequate type II cell maturation results in the neonatal respiratory
      distress syndrome, which is frequently fatal. We have used serial ultrathin
      sectioning, electron microscopy, and three-dimensional reconstructions to study
      the ultrastructural features of maturation of rat type II cells from a single rat
      each at age gestational day 20 through adult stages. We found evidence over this
      time span for compartmentation of several secretory granule precursors within
      type II cells. Changes in the polarization of lamellar bodies were observed over
      the time period studied. We also found marked gestational changes in the number
      and morphology of type II cell cytoplasmic processes that perforate the basement
      membrane. Type II cell mitochondria changed in shape during postnatal development
      from single, spherical to complex, branched structures. Volume composition
      obtained from serial sections of a small number of type II cells agreed closely
      with published morphometric data, indicating that throughout the animal's
      lifespan, type II cells are a homogenous population.

PMID- 1996655
TI  - Cytokine signaling in lung: transforming growth factor-beta secretion by lung
      fibroblasts.
AB  - Control of growth and phenotypic expression of interstitial fibroblasts is a
      critical determinant of lung architecture and physiology during processes of
      growth and remodeling. We examined the ability of lung fibroblasts to produce
      transforming growth factor-beta (TGF-beta), a cytokine that is known to modulate
      proliferation and phenotypic expression of mesenchymal cells. Cultures of
      fibroblasts isolated from rat lungs spontaneously secrete TGF-beta as measured in
      the standard bioassay of anchorage-independent growth of normal rat kidney (NRK)
      cells in soft agar. Rat lung fibroblasts secrete TGF-beta in an inactive
      precursor form. Fibroblasts cultured from adult and fetal rat lungs produced
      comparable amounts of TGF-beta. The ability of lung fibroblast supernatant fluids
      to induce colony formation in soft agar could be completely neutralized by
      preincubation of samples with anti-TGF-beta immunoglobulin (Ig). Anti-platelet
      derived growth factor IgG had no effect on anchorage-independent growth of NRK
      cells driven by rat fibroblast culture supernatant samples. These results
      indicate that TGF-beta does not require the presence of and interaction with
      secondary cytokines for its activity. In contrast to the results obtained with
      rat cells, neither human fetal nor adult lung fibroblasts secreted detectable
      amount of active TGF-beta or its inactive precursor. This was not due to the
      presence of TGF-beta inhibitors in fibroblast culture media, because the addition
      of purified porcine TGF-beta to conditioned medium from human lung fibroblast
      cultures yielded the expected increase in NRK cell growth in soft agar. These
      results point to differing cytokine control patterns in the lungs of the two
      species.

PMID- 1996656
TI  - Secretory granule calcium loss after isolation of rat alveolar type II cells.
AB  - Morphological change and lamellar body loss suggests that alveolar type II cells
      rapidly de- or redifferentiate after several days of primary culture. To
      determine whether type II cells or lamellar body compositional changes precede
      these obvious morphological changes, we examined the in situ elemental
      composition of lamellar bodies and type II cells from intact lung and at
      different times after isolation using electron probe microanalysis (EPMA).
      Isolated cells were prepared by standard methods and plated on either tissue
      culture plastic or kept in suspension with stirrer flasks. Cell pellets obtained
      at 0, 3, 24, and 48 h after isolation were rapidly frozen, and thin freeze-dried
      cryosections were prepared and examined cold in a transmission electron
      microscope equipped for EPMA. Eight to ten type II cells from each of three to
      four different preparations for each time period were analyzed. A rapid,
      progressive, and sustained fall in lamellar body calcium and sulfur content
      occurred by 48 h of primary culture, suggesting rapid alteration in calcium and
      protein metabolism by type II cells and/or lamellar bodies after isolation. Also,
      marked changes in type II cell cytoplasmic Na and K occurred in freshly isolated
      cells, with incomplete normalization by 48 h. Culture on laminin-enriched
      Matrigel for 1 wk increased both lamellar body calcium or sulfur content, but 100
      nM dexamethasone had no effect. Lamellar body calcium accumulation appears to be
      a very sensitive index of differentiated type II cell function.

PMID- 1996657
TI  - Protein kinase C activation allows pulmonary artery smooth muscle cells to
      proliferate to hypoxia.
AB  - Pulmonary artery (PA) smooth muscle cell (SMC) proliferation occurs with hypoxic
      pulmonary hypertension in vivo. However, proliferation of cultured PA SMC to
      hypoxia has not been demonstrated, and thus the mechanism by which these cells
      respond to hypoxia is unknown. Because protein kinase C (PKC) plays a role in
      intracellular transduction of proliferative signals, we asked whether PKC
      activation 1) causes proliferation of bovine PA SMC and 2) is important in PA SMC
      proliferative response to hypoxia. By measuring [3H]thymidine incorporation and
      cell counts, we found that quiescent PA SMC from four different cows proliferated
      with the PKC activator, phorbol 12-myristate 13-acetate (PMA), in a concentration
      dependent manner. The proliferation was blocked with a PKC inhibitor,
      dihydrosphingosine, or by downregulating SMC PKC. We tested whether "priming" PA
      SMC by PKC activation was required for in vitro SMC proliferative response to
      hypoxia. Each SMC population was treated with PMA and then exposed for 24 h to
      20, 10, 7, 3 or 0% O2. These cells proliferated with hypoxia reaching a peak
      response at 3% O2. The magnitude of the response to PMA and hypoxia was different
      for each cell population tested. No hypoxic proliferation occurred in control
      cells (no PMA). Dihydrosphingosine blocked the hypoxic response to the same
      extent that it inhibited the initial PMA conditioning stimulus. PKC-downregulated
      PA SMC did not proliferate to PMA or to subsequent hypoxia. The hypoxic response
      was not due to a reduction in O2 radical-mediated antiproliferative effect;
      rather, the PMA-primed cells seemed to "acquire" the ability to directly sense
      hypoxia and proliferate. In summary, PKC activation caused proliferation of PA
      SMC in vitro and allowed an additional proliferative response to hypoxia.
      Activation of PKC may be a requisite step for PA SMC to respond directly to
      hypoxia.

PMID- 1996658
TI  - Dexamethasone in vivo raises surfactant protein B mRNA in alveolar and
      bronchiolar epithelium.
AB  - Glucocorticoids enhance the rate of maturation of the fetal lung, in part, by
      increasing production of surfactant by type II cells. We have examined the effect
      of in vivo dexamethasone treatment on mRNA levels for the hydrophobic surfactant
      protein, SP-B, in rat lung and compared the data to similar measurements of SP-A
      mRNA. Rats of known gestational and postnatal ages were injected
      intraperitoneally with dexamethasone (2 mg/kg) and killed after 24 h. SP-B mRNA
      levels in the lungs were determined by RNA blotting using rat SP-A and SP-B cDNA
      probes. SP-B mRNA levels increased 5.2-fold when 163 pairs of animals of all ages
      were examined. SP-B mRNA increases in fetuses (107 pairs) and postnatal animals
      (56 pairs) were 8.4- and 2.1-fold, respectively (P less than 0.0001). The high
      levels of stimulation in fetal lungs were largely due to high increases on
      gestational days 18 and 19 when the control levels are very low. There were no
      detectable gender differences in the population as a whole. Tissue in situ
      hybridization showed that type II cells, as well as some bronchiolar cells,
      responded to dexamethasone treatment throughout life. The significance and the
      reasons for the presence and hormonal responsiveness of SP-B in the bronchiolar
      epithelium are intriguing and warrant further investigation.

PMID- 1996659
TI  - Surfactant apoprotein in adult rat lung compartments is increased by
      dexamethasone.
AB  - The distribution of the major surfactant apoprotein (SP-A) in adult rat lung was
      determined in order to gain insight into its metabolism, including packaging of
      SP-A into lamellar bodies. The effect of glucocorticoid treatment on surfactant
      apoprotein was studied to test whether regulation of surfactant apoprotein genes,
      which has been described for the fetal lung, can be demonstrated in the adult
      animal. We measured the amounts of immunoreactive SP-A in several lung tissue
      compartments and lavage fractions from control animals and from the lungs of rats
      given dexamethasone for 1 wk. Protein and phospholipids were measured, SP-A was
      quantitated with a noncompetitive enzyme-linked immunoabsorbent assay (ELISA) and
      SP-A, SP-B, and SP-C mRNAs were estimated by Northern blotting. We found an 85
      fold concentration of SP-A in a lamellar body-rich fraction compared with lung
      tissue homogenate and we calculated that as much as one-half of all the tissue SP
      A might be accounted for by a lamellar body pool. After 1 wk of dexamethasone
      treatment, there was an increase in adult rat lung SP-A, SP-B, and SP-C mRNA and
      a substantial increase in tissue and lavage fluid immunoreactive SP-A pools.
      Lamellar body fraction SP-A content per lung was 1.4-fold higher after
      dexamethasone, and there was a fivefold increase in the lavage SP-A pool, much of
      which was inseparable from the alveolar macrophages. We conclude that SP-A is
      concentrated in the lamellar bodies of type II cells, that dexamethasone
      treatment increased all surfactant mRNAs, and that it increased SP-A content in
      adult rat lung.

PMID- 1996660
TI  - Effect of in vitro preconditioning on tracheal smooth muscle responsiveness.
AB  - We evaluated the effect of preconditioning of the isometric contractile response
      of canine tracheal smooth muscle (TSM) in vitro. Strips of epithelium-free TSM (n
      = 90) were excised from 16 anesthetized dogs and fixed isometrically in tissue
      perfusion chambers. Experiments were performed using methods previously reported
      in which the following parameters were investigated: 1) quiescent equilibration
      time in the perfusion chamber (0-120 min); 2) effect of repeated exchange of
      perfusate; 3) method of determining the optimal resting length (Lmax) for
      presetting of resting tension (RT); 4) effect of precontraction during the
      equilibration phase on the contractile response to agonists administered
      subsequently; and 5) method of determining RT on the response to muscarinic
      stimulation. When other variables were uniform, neither equilibration time nor
      perfusate exchange affected potency or efficacy of the response generated
      subsequently to acetylcholine (ACh). However, both potency (range of EC50: -5.71
      +/- 0.14 log M to -6.52 +/- 0.24 log M; P less than 0.02) and efficacy (range of
      maximal active tension: 1,143 +/- 268 g/cm2 to 2,878 +/- 151 g/cm2; P less than
      0.001) of ACh were altered substantially as a result of the method used to
      estimate Lmax. Repeated precontraction by electrical field stimulation or with
      127 mM KCl did not alter potency or efficacy of contraction elicited by ACh.
      Maximal active tension generated with 10(-3) M ACh was 2,878 +/- 151 g/cm2 after
      12-15 tetanizing field stimulations and 2,696 +/- 198 g/cm2 after 5-7
      contractions with 127 mM KCl (P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1996662
TI  - Evidence that fatty acid chain length is a type II cell lipid-sorting signal.
AB  - This study was undertaken to determine those structural features of phospholipid
      molecules which influence their enrichment in type II cell lamellar body
      material. Cultured fetal rabbit lung tissue was labeled with [1-14C]acetate, type
      II cells were isolated, and extracellular lamellar body and microsomal fractions
      were prepared. Radiolabeled molecular species of phosphatidylcholine (PC) and
      phosphatidylethanolamine were analyzed by high-performance liquid chromatography
      (HPLC), followed by silver nitrate thin-layer chromatography of HPLC peak
      fractions that overlapped. Compared with microsomes, lamellar body PC was
      selectively enriched with molecular species containing 14- and 16-carbon fatty
      acids and depleted of species containing 18-carbon fatty acids. Palmitoleic acid
      and an ether linkage positively influenced the enrichment of PC molecular species
      in the lamellar body material, but these structural features were secondary to
      the predominant influence of fatty acid chain length. In vivo, lung tissue
      normally contains low levels of palmitoleic acid; hence most unsaturated fatty
      acids are 18-carbons or longer. A cellular lipid-sorting mechanism that selects
      PCs by recognition of 14- and 16-carbon fatty acid chains (and not by recognition
      of fatty acid saturation) should serve to enrich the resulting pulmonary
      surfactant with disaturated molecular species of PC.

PMID- 1996661
TI  - Glucocorticoid enhances pulmonary surfactant protein B gene transcription.
AB  - The effect of glucocorticoid on the regulation of pulmonary surfactant protein B
      (SP-B) synthesis was studied in a human pulmonary adenocarcinoma cell line.
      Northern blot analysis demonstrated a marked increase in SP-B mRNA expression
      after treatment with dexamethasone for 48 h. Actinomycin D, puromycin, or
      cycloheximide blocked the induction of SP-B mRNA by glucocorticoid. Nuclear run
      on experiments demonstrated that the effects of dexamethasone on SP-B mRNA were
      due in part to increased transcription of the SP-B gene. However, during this
      time period, there was a discrepancy between SP-B gene transcription, which was
      increased only 2- to 4-fold, and SP-B mRNA, which increased 60- to 150-fold after
      treatment with dexamethasone. In the presence of actinomycin D, SP-B mRNA was
      relatively stable, decreasing slowly in the presence or absence of
      glucocorticoid. In contrast to the relative stability of SP-B mRNA in the
      presence of actinomycin D, SP-B mRNA was markedly decreased after exposure to
      puromycin, supporting the premise that continued protein synthesis, rather than
      transcription alone, is required for maintenance of SP-B mRNA levels. Induction
      of SP-B expression by glucocorticoids was dependent on enhanced SP-B gene
      transcription and was also dependent on continued protein synthesis. The
      discrepancy between the relative enhancement of SP-B transcription and SP-B mRNA
      suggests that posttranscriptional factors influence SP-B expression in this cell
      line.

PMID- 1996663
TI  - Adenosine A2-receptor-mediated phosphatidylcholine secretion in type II
      pneumocytes.
AB  - Adenosine and its analogues stimulate phosphatidylcholine secretion in cultured
      rat type II pneumocytes. There is evidence that this effect is mediated by A2
      receptors. We have now employed the radioligand 5'(N-ethylcarboxyamido)adenosine
      (NECA) in an attempt to study the adenosine receptor in a membrane fraction of
      type II cells. Specific binding of [3H]-NECA was saturable with a total binding
      capacity (Bmax) of 4.91 pmol/mg protein and a dissociation constant (Kd) of 240
      nM. The Kd was similar to the concentration of NECA which half-maximally
      stimulated phosphatidylcholine secretion (EC50, 150 nM). Although the relative
      potency of adenosine analogues in displacing bound [3H]NECA was consistent with
      that expected at an A2 receptor, there were discrepancies between binding and
      function with respect to some agonists as well as the antagonist xanthine amine
      congener (XAC). This together with the unusually high Bmax suggests that the NECA
      binding site is not the adenosine receptor mediating phosphatidylcholine
      secretion. The receptor was further characterized functionally by measuring its
      antagonist dissociation constant (Kb). KbS for XAC inhibition of the effects of
      NECA, N6-(L-2-phenylisopropyl)adenosine, and adenosine on phosphatidylcholine
      secretion were 19 +/- 8, 24 +/- 11, and 6 +/- 12 nM, respectively, suggesting
      that all three agonists act at the same receptor. The Kb value allowed comparison
      of the receptor in type II cells with that in other tissues and revealed that it
      was similar to the A2 receptor previously described in human platelets. These
      functional data further characterize and are consistent with a physiological role
      for the adenosine A2 receptor in the regulation of lung surfactant secretion.

PMID- 1996665
TI  - Role of endothelin 1 in regulating rabbit airway contractility.
AB  - Endothelin 1 (ET-1) is a potent vasoconstrictor peptide recently isolated from
      vascular endothelial cells. Because its role and mechanisms of action in
      regulating airway contractility remain to be identified, we examined the
      contractile effects of ET-1 in isolated rabbit tracheal smooth muscle (TSM)
      segments. In TSM under passive tension, ET-1 elicited dose-dependent contractions
      with a mean +/- SE -log 50% of maximal response value of 7.82 +/- 0.13 vs. a
      value of 5.61 +/- 0.07 -log M for acetylcholine (ACh). In TSM half-maximally
      contracted with ACh, however, ET-1 exerted dual and opposing contractile effects.
      Lower doses of ET-1 (less than or equal to 10(-9) M) produced a 74.2 +/- 16.6%
      decrease in active TSM tension. This relaxant response to ET-1 was associated
      with an accelerated accumulation of prostaglandin (PG) I2 and PGE2 and was
      attenuated by cyclooxygenase inhibition with indomethacin (10(-5) M). The
      combination of indomethacin and removal of the airway epithelium completely
      inhibited the TSM relaxant response to ET-1. In contrast, higher doses of ET-1
      (greater than 10(-9) M) induced airway contractions that were attenuated by the
      Ca2+ channel blockers nifedipine (10(-5) M) and diltiazem (10(-5) M) and ablated
      in Ca2(+)-free buffer. Moreover, ET-1-induced TSM contractions were inhibited by
      the protein kinase C (PK-C) antagonists 1-(5-isoquinolinylsulfonyl)-2
      methylpiperazine, and staurosporine.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1996664
TI  - Induction of ceruloplasmin gene expression in rat lung during inflammation and
      hyperoxia.
AB  - To determine the effect of inflammation on extrahepatic ceruloplasmin gene
      expression we examined the ceruloplasmin mRNA content of adult rat tissues after
      endotoxin injection. Within 8 h of a dose of endotoxin ceruloplasmin mRNA content
      increased in the liver as expected and was also detectable in the lung. The
      effect of endotoxin was tissue specific because ceruloplasmin mRNA was not
      consistently detected in other extrahepatic tissues. The kinetics of
      ceruloplasmin mRNA accumulation in lung and liver tissue were similar with a
      maximum seven- to ninefold increase in ceruloplasmin mRNA content in each tissue
      within 24 h. The relative rate of ceruloplasmin gene transcription was increased
      in both tissues within 3 h of endotoxin, suggesting similar mechanisms of
      regulation of ceruloplasmin gene expression during inflammation. One cellular
      site of ceruloplasmin production in the inflamed lung was found to be the
      alveolar macrophage, which expressed the ceruloplasmin gene and synthesized
      ceruloplasmin protein in response to endotoxin in vitro. Because of these
      findings we also examined the effects of hyperoxia on ceruloplasmin gene
      expression. Exposure of adult rats to 95% O2 resulted in a five- to sixfold
      induction of ceruloplasmin mRNA in lung tissue within 46 h, and this response was
      time dependent, reaching maximum values at 86 h. Hyperoxic induction of
      ceruloplasmin mRNA was specific to the lung and not the result of systemic
      inflammation because hepatic ceruloplasmin mRNA content remained constant. These
      data indicate that the lung is a prominent site of ceruloplasmin gene expression
      during inflammation and hyperoxia and suggest that this protein may play a
      previously unappreciated role in pulmonary injury or repair.

PMID- 1996666
TI  - Amiloride-inhibitable Na+ conductive pathways in alveolar type II pneumocytes.
AB  - The purpose of these studies was to document the existence of electrogenic Na+
      uptake by membrane vesicles of rabbit alveolar type II (ATII) cells and the
      extent to which this process was inhibited by amiloride. ATII cells (greater than
      85% pure) were obtained by elastase digestion of lung tissue followed by Percoll
      centrifugation, and an enriched plasma membrane vesicle fraction was obtained by
      differential centrifugation. 22Na+ uptake into these vesicles was measured in the
      presence of a negative inside membrane potential, produced by the addition of the
      K+ ionophore valinomycin (10 microM) after all external K+ was removed.
      Electrogenic (valinomycin-sensitive) Na+ uptake (ELNa) was defined as the
      difference in uptake in the presence and absence of valinomycin. ELNa, normalized
      per milligram protein, was twice as high across ATII cells than alveolar
      macrophage membrane vesicles, was inhibited by amiloride (50% inhibitory
      concentration = 10 microM), and was decreased in the presence of an outwardly
      directed proton gradient (pHin 6.8; pHout 7.8), suggesting that it was not
      mediated by Na(+)-H+ antiport. Furthermore, ELNa was equally inhibited by
      increasing concentrations of amiloride and benzamil but was more sensitive to 5
      (N-ethyl-N-isopropyl)-2'-4'-amiloride in concentrations of 10-1,000 microM. These
      findings indicate that a fraction of Na+ transport across ATII membrane vesicles
      occurs through a conductive pathway, probably a channel, that has different
      sensitivity to amiloride and its analogues than the previously described
      epithelial high amiloride-affinity Na+ channel.

PMID- 1996667
TI  - Selectivity and direction: plasma membranes in renal transport.
AB  - Studies using isolated renal plasma membranes are now considered to be essential
      methods for elucidating renal transport processes in health and disease. This
      review first describes the development of methods and concepts in working with
      isolated plasma membranes some 20 years ago, when few people believed that it was
      actually possible to isolate plasma membranes at all. The concepts we developed
      at that time are still applicable today, and I believe they are therefore worth
      reiterating. The description of the past leads to a presentation of current ideas
      about the interrelationship between selectivity of renal plasma membranes and
      direction of transepithelial transport. Finally, the future direction of kidney
      research is discussed in view of recent physiological, biochemical, and genetic
      studies.

PMID- 1996668
TI  - Site and mechanism of action of epidermal growth factor in rabbit cortical
      collecting duct.
AB  - To examine the exact target cell and mechanism of action of epidermal growth
      factor (EGF) in the isolated cortical collecting duct from rabbit kidney, we
      compared electrical properties of collecting duct (CD) cells (principal cells)
      and intercalated (IC) cells in absence and presence of EGF at 10(-8) M.
      Differentiation of CD and IC cells was based on values of basolateral membrane
      voltage (Vb) and fractional apical membrane resistance (fRa). In CD cells, upon
      addition of EGF to bath, lumen-negative transepithelial voltage (VT) was
      decreased from -8.0 +/- 1.9 to -2.4 +/- 1.3 mV (n = 22, P less than 0.001), but
      Vb was little changed (from -85.1 +/- 2.8 to -83.1 +/- 2.7 mV, n = 19),
      indicating that EGF in bath mainly caused changes in apical membrane voltage. In
      addition, peritubular EGF increased transepithelial resistance (RT) from 132.9 +/
      15.8 to 153.8 +/- 18.4 omega.cm2 (n = 16, P less than 0.001) as well as fRa from
      0.31 +/- 0.06 to 0.39 +/- 0.07 (n = 12, P less than 0.01). These actions of EGF
      were prevented by pretreatment with 50 microM luminal amiloride. Luminal EGF had
      no effects on VT, Vb, RT, or fRa of CD cells. In IC cells, upon addition of EGF
      to bath, neither Vb nor fRa was affected. From these results, we conclude that
      EGF acts on the CD cell at the basolateral border and inhibits mainly the
      amiloride-sensitive Na+ conductance in the apical membrane.

PMID- 1996669
TI  - Stimulation of renin release by hyperkalemia in the nonfiltering kidney.
AB  - This study was designed to analyze the acute effects of hyperkalemia on renin
      release in the normal filtering kidney and the nonfiltering kidney. Plasma K was
      increased by acute intravenous KCl infusion. In the normal filtering kidney
      experiment plasma K was 5.7 vs. 3.5 meq/l. Hyperkalemia resulted in a 45%
      increase in renal blood flow (RBF) and a 35% increase in glomerular filtration
      rate (GFR) at the 120-mmHg pressure level. Renin release was significantly
      greater in the hyperkalemic group than in the control group (P less than 0.01)
      with the greatest effect over the lower pressure range. In the nonfiltering
      kidney experiment plasma K was 6.09 vs. 3.5 meq/l. RBF was 33% greater in the
      hyperkalemic than in the normokalemic group at the 130-mmHg pressure level. Renin
      release was also greater in the hyperkalemic group than in the normokalemic group
      (P less than 0.01). However, unlike the normal filtering kidney experiments, in
      the nonfiltering kidneys the difference in renin release was most prominent at
      the highest level of renal perfusion pressure. These experiments demonstrate that
      acute hyperkalemia can cause renal vasodilation and stimulate renin release in
      both filtering and nonfiltering kidney preparations and that potassium may affect
      renin release both through a direct effect on the juxtaglomerular cells and
      indirectly by affecting delivery of fluid and/or NaCl to the macula densa.

PMID- 1996670
TI  - Increased extracellular matrix synthesis and mRNA in mesangial cells grown in
      high-glucose medium.
AB  - Nodular expansion of glomerular mesangium with increased amounts of extracellular
      matrix (ECM) material is pathognomic of diabetic nephropathy. The precise
      mechanisms involved in this accumulation are unknown. Recently, we reported using
      a solid-phase enzyme-linked immunosorbent assay (ELISA) technique that glomerular
      mesangial cells, the principal cell type residing in glomerular mesangium,
      accumulate 50-60% more fibronectin (FN), laminin (LM), and type IV collagen (T
      IV) when cultured in medium containing high glucose (30 mM) (S. H. Ayo, R. A.
      Rodnik, J. Garoni, W. F. Glass II, and J. I. Kreiberg. Am. J. Pathol. 136: 1339
      1348, 1990). ECM assembly is controlled by its rate of synthesis and degradation,
      as well as its binding and rate of incorporation into the ECM. To elucidate the
      mechanisms involved, pulse-chase experiments were designed to estimate ECM
      protein synthesis from the incorporation of Trans-35S [( 35S]methionine,
      [35S]cysteine) into immunoprecipitated FN, LM, and T-IV. mRNA levels were
      examined, and degradation rates were estimated from the disappearance of
      radioactivity from matrix proteins in mesangial cells previously incubated with
      Trans-35S. One week of growth in 30 mM glucose resulted in approximately 40-50%
      increase in the synthesis of all three matrix proteins compared with 10 mM
      glucose-grown cells. This was accompanied by a significant increase in the
      transcripts for all three matrix proteins (approximately twofold). The specific
      activity of the radiolabel in trichloroacetic acid-precipitable cell protein
      showed no difference between cells grown in 10 or 30 mM glucose, indicating that
      total protein synthesis was unchanged. After 1 wk, the rate of FN, LM, and T-IV
      collagen degradation was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1996671
TI  - Release of acetylcholine from isolated canine renal tissue.
AB  - Slices of canine kidney were incubated with [3H]choline and Ringer-Krebs solution
      for 30 min. Secretion of [3H]acetylcholine ([3H]ACh) was evoked by either 1) an
      electrical field stimulation (0.5-1 Hz, 2 ms, 20 V) or 2) high-potassium (57 mM)
      superfusion for 3 min to depolarize nerve terminals. With these stimulatory
      schedules, the 3H release mainly consists of [3H]-ACh. The ACh release is Ca2+
      dependent and blocked in presence of a Mg2(+)-rich medium. Thus suppression of
      ongoing neuronal activity by tetrodotoxin and blockade of nicotinic receptors by
      hexamethonium reduced the electrically evoked ACh release. With both stimulatory
      procedures, the secretory response was modified by pilocarpine and atropine. In
      addition, the release of [3H]ACh produced by electrical field stimulation was
      inhibited by neostigmine, indicating the presence of functional presynaptic
      receptors in cholinergic putative terminals. Activation of these receptors
      depresses ACh secretion. The disruption of extrinsic renal nerves 7 days before
      did not diminish [3H]ACh release caused by K+ stimulation and, conversely,
      increased [3H]ACh released by electrical field stimulation. These data support
      the presumed existence of cholinergic nerve terminals in the canine kidney that
      can release ACh under suitable conditions of stimulation.

PMID- 1996672
TI  - Rat kidney band 3 mRNA modulation in chronic respiratory acidosis.
AB  - Recent evidence indicates the existence of a protein related to the erythroid
      chloride-bicarbonate exchanger (band 3 protein) in the basolateral aspect of type
      A intercalated cells of the distal nephron. To probe the possible participation
      of this transporter in the renal adaptation to chronic hypercapnia, we examined
      the steady-state abundance of band 3 mRNA in the kidney during respiratory
      acidosis of variable duration. Total RNA was isolated from renal cortex and
      medulla of rats maintained in a 10% CO2 atmosphere for 2 or 5 days and from
      contemporaneous controls. The RNA was analyzed by Northern blot assay using cDNA
      probes for band 3 and beta-actin genes. Using a 3' cDNA probe encoding the
      membrane-associated domain of band 3 protein that is involved in anion exchange,
      we found a two- to threefold increase in steady-state mRNA levels (whether or not
      correction for the beta-actin signals was applied) in renal cortex and medulla at
      5 days of hypercapnia. Similar, but less definitive, increases were observed at
      the 2-day time point. Using a 5' cDNA probe encoding an erythroid-protein segment
      absent from the kidney band 3 major transcript, we detected meager hybridization
      in renal tissue and no measurable variation during hypercapnia. Use of splenic
      RNA as a positive control for the 5' probe disclosed marked reduction of band 3
      mRNA levels in hypercapnia, indicating organ specificity of band 3 gene
      expression. We conclude that steady-state levels of kidney band 3 mRNA increase
      in chronic respiratory acidosis as a result of transcriptional or
      posttranscriptional regulatory mechanisms. This adaptation might be involved in
      the augmentation of renal acidification characteristic of chronic hypercapnia.

PMID- 1996673
TI  - PKC and Pi deprivation modulate differently the ubiquitous Na-dependent Pi uptake
      in MDCK cells.
AB  - The role of protein kinase C (PKC) in the modulation of the ubiquitous sodium
      dependent phosphate transport and in adaptation of that transport to phosphate
      deprivation was investigated in MDCK cells. Phorbol myristate acetate (PMA) had a
      biphasic effect on sodium-dependent phosphate uptake characterized by early
      inhibition (-25% at 1 h) followed by late stimulation (2.3-fold at 15 h). Late
      stimulation was related to a decreased apparent affinity (Km) with unchanged
      maximal velocity (Vmax). The 15-h stimulation of phosphate uptake was also
      induced by an initial 1-h PMA treatment followed by a 14-h washout of PMA or by
      R59 022. The stimulation was inhibited by PKC downregulation. PMA stimulation was
      dependent on protein synthesis but not on transcription, as shown by the
      respective effects of cycloheximide, 3'-deoxyadenosine, and actinomycin D. In
      phosphate-deprived cells PMA had also a biphasic effect. A potentiation of PMA
      stimulation of phosphate uptake with phosphate deprivation was observed.
      Adaptation to phosphate deprivation was not prevented by PKC downregulation.
      Cytosolic and membranous PKC activities were not changed by 15-h phosphate
      deprivation. We conclude that 1) PKC modulates sodium-dependent phosphate uptake
      in MDCK cells, and 2) phosphate deprivation and PKC modulation of sodium
      dependent phosphate uptake involve different cellular pathways; that is,
      phosphate deprivation acts through gene regulation, and PKC acts through
      translation regulation.

PMID- 1996674
TI  - Isolation of nephrocalcin from kidney tissue of nine vertebrate species.
AB  - Nephrocalcin (NC), a urinary calcium oxalate monohydrate (COM) crystal growth
      inhibitor, was purified from kidneys of nine vertebrate species including humans.
      All isolates were glycoproteins with high contents of aspartic and glutamic acids
      and small amounts of basic and aromatic amino acids. Carbohydrate contents ranged
      from 4 to 16 wt% among the different species, but all contained fucose, mannose,
      galactose, glucose, galactosamine, glucosamine, and N-acetylneuraminic acid.
      Although amino acid and carbohydrate compositions were similar, dissociation
      constants derived from calcium oxalate monohydrate inhibition varied between 10(
      7) and 10(-8) M, and highest affinity could be related to highest ability of the
      kidney of origin to concentrate urine. Using an antibody raised against NC from
      human kidney tissue culture medium, we found strong immunoreactivity with two
      species, pigs and sheep. Thus far all vertebrate kidneys possess COM growth
      inhibiting material that seems to be of glycoprotein character, and all the
      glycoproteins isolated so far share similar features, suggesting NC-like proteins
      are a well-conserved trait.

PMID- 1996675
TI  - Pathophysiology of vascular smooth muscle in renin promoter-T-antigen transgenic
      mice.
AB  - The pathophysiological consequence of targeted production of SV-40 T-antigen to
      renin-expressing cells in the kidney of transgenic mice is reported. A
      histopathologic analysis of the kidney from adult transgenic mice (12-16 wk old)
      revealed the presence of severe vascular lesions manifested by marked atypical
      hyperplasia of vascular smooth muscle. The levels of plasma renin, kidney renin,
      and kidney renin mRNA were examined in 6- and 9-wk-old transgenic mice and were
      found to be significantly lower than their age-matched non-transgenic littermates
      and were nonresponsive to captopril treatment. However, there was no significant
      difference in conscious mean arterial pressure between transgenic and non
      transgenic mice. The levels of renal renin mRNA in transgenics and nontransgenic
      littermates were compared throughout ontogeny and were found to be equal in
      newborns, elevated 3- to 5-fold in 1-wk-old transgenics, and yet decreased 10
      fold by 6 wk of age in transgenic mice. Expression of the transgene in the kidney
      exhibited the proper developmental pattern and was properly restricted to
      juxtaglomerular cells in neonatal mice. Nevertheless, in adult mice, T-antigen
      containing cells were found throughout the entire renal arterial tree. The
      observed ability of renal vascular cells to be recruited to express both renin
      and T-antigen suggests a mechanism that can explain the development of the renal
      pathology in these mice.

PMID- 1996676
TI  - Renal Na-myo-inositol cotransporter mRNA expression in Xenopus oocytes:
      regulation by hypertonicity.
AB  - Canine renal cells in culture (MDCK cells) accumulate organic osmolytes,
      including myo-inositol (MI), in response to hypertonic stress. When medium
      tonicity is increased, intracellular concentration of MI rises because
      hypertonicity elicits increased uptake of MI via Na-MI cotransporter(s). To study
      the mechanism for this increase in cotransporter activity, poly(A)+ RNA isolated
      from MDCK cells maintained in hypertonic or isotonic medium was injected into
      Xenopus oocytes, and Na-dependent MI uptake was measured 3-5 days later. Poly(A)+
      RNA from hypertonic cells induced clear expression of the cotransporter. In
      contrast, oocytes injected with poly(A)+ RNA isolated from MDCK cells maintained
      in isotonic medium exhibited cotransporter activity like oocytes injected with
      water. Upon size fractionation of RNA, peak activity appeared in a fraction that
      contained poly(A)+ RNA with median size of approximately 4 kilobases. Na
      dependent MI uptake by poly(A)+ RNA-injected oocytes was inhibited by both
      phlorizin and phloretin. We suggest that hypertonicity-induced upregulation of
      the Na-MI cotransporter involves an increase in mRNA and synthesis of
      cotransporter protein(s).

PMID- 1996677
TI  - Permeabilities of rat collecting duct segments to NH3 and NH4+.
AB  - We have measured NH3 and NH4+ permeability coefficients in collecting ducts from
      the cortex, outer medulla, and inner medulla of the rat kidney. Isolated
      collecting duct segments of the rat were perfused with bicarbonate-buffered
      solutions containing carbonic anhydrase to eliminate any pH disequilibrium in the
      tubule lumen. NH3 or NH4+ concentration gradients were set up between the bath
      and the lumen. By measuring the total CO2 and total ammonia concentrations in the
      bath, the perfusate, and collected fluid, the NH3 and NH4+ concentrations were
      determined. Then, using the flow rate in the tubule and the tubule dimensions, we
      calculated the apparent permeability in each collecting duct segment for NH3 and
      NH4+. The NH3 permeabilities were as follows: 0.002 cm/s in the inner medullary
      collecting duct, 0.012 cm/s in the outer medullary collecting duct, and 0.024
      cm/s in the cortical collecting duct. The NH4+ permeabilities for all segments
      were on the order of 10(-5) cm/s or less. The relative permeability values for
      the two ammonium species are consistent with the view that the secretion observed
      in vivo in collecting ducts is due to passive diffusion of NH3 from the
      interstitium to the lumen of the duct, parallel with H+ secretion.

PMID- 1996678
TI  - Suitability of tritiated inulin for determination of glomerular filtration rate.
AB  - Purity of different batches of [3H]inulin delivered from leading manufacturers
      was elevated with a chromatographic method (Sephadex G-25 column) that allowed
      simultaneous analysis of cold inulin, [3H]inulin, and [14C]inulin in the same
      run. Among four batches of [3H]inulin received within 5 mo, two were found
      relatively pure, whereas two were partly decomposed to lower-molecular-weight
      fragments. The chromatographic profile of pure isotopes was not significantly
      affected by redistribution and freeze drying, nor by subsequent storage in the
      freeze-dried state at -20 degrees C for up to 5 mo, nor by incubation in aqueous
      solution at 37 degrees C for 24 h. Three batches of [3H]inulin with different
      grades of decomposition (noninulin percentages 13%, 38%, and 61%, respectively)
      were selected for clearance experiments and infused simultaneously with cold and
      undecomposed [14C]inulin to conscious rats. [14C]inulin had a significantly
      higher clearance than cold inulin (+7.6 +/- 0.6%) and relatively pure [3H]inulin
      (+12.4 +/- 0.4%). Decomposed [3H]inulin isotopes progressively underestimated
      clearance of cold inulin to an extent related to the degree of decomposition.
      Thus at the end of the 5-h clearance experiment, ratios between clearance of
      tracer and of cold inulin were 0.92, 0.71, and 0.60 for the three 3H isotopes,
      respectively. This study indicates that [3H]inulin delivered from leading
      manufacturers may be decomposed to an extent that invalidates its use as a marker
      for glomerular filtration rate (GFR). It is thus necessary to check the purity
      routinely before use. Within the same rat, clearance of undecomposed [3H]inulin
      and [14C]inulin may differ by 12%, and for this reason they should not be used
      interchangeably as GFR markers.

PMID- 1996679
TI  - Sympathetic-parasympathetic interaction and accentuated antagonism in conscious
      dogs.
AB  - The heart rate response to vagal stimulation and the interaction with sympathetic
      activity was evaluated in conscious dogs at rest and during exercise; the latter
      was used as a tool to physiologically elevate sympathetic activity. In 20 dogs
      with a healed myocardial infarction and in 7 healthy dogs a bipolar electrode was
      chronically implanted around the right cervical vagus. Vagal stimulation (3 ms;
      2.1 +/- 0.7 mA; 2, 4, 6, 8, 10, 12 Hz) was performed while dogs stood on the
      treadmill (heart rate 120 +/- 25 beats/min) and while they exercised (201 +/- 17
      beats/min). Gradual increases of the frequency of vagal stimulation gradually
      enhanced the inhibitory effect on heart rate both before and during exercise.
      During exercise, heart rate reduction was significantly greater than that
      produced at rest at any frequency of stimulation (P less than 0.001). This
      difference widened as the frequency of stimulation increased and the interaction
      with or without the presence of exercise was significant (P less than 0.02).
      Vagal stimulation produced similar effects in the seven dogs without myocardial
      infarction. These data demonstrate that the vagal-sympathetic "accentuated
      antagonism" described in anesthetized animals is also present in conscious dogs.

PMID- 1996680
TI  - Influence of experimental diabetes on sarcoplasmic reticulum function in rat
      ventricular muscle.
AB  - We examined whether the decrease in cardiac contractility in streptozotocin
      induced diabetes in the rat is accompanied by reduced or excessive loading of the
      sarcoplasmic reticulum (SR) with Ca2+. Pooled SR Ca2+ content and fractional
      release on stimulation were estimated with rapid cooling contracture (RCC) and
      twitch height measurements, respectively. Interval-force relation was studied to
      assess the ability of diabetic tissue to alter the relative contribution of SR
      Ca2+ for contraction. Two months after injection with streptozotocin, peak
      isometric contraction and steady-state RCC decreased in parallel to approximately
      50% of control values. The time to peak force development and complete relaxation
      was prolonged to 156 and 161% in diabetes in the presence of 1.25 and 2.5 mM
      extracellular Ca2+ concentration [Ca2+]o, respectively. A stepwise increase in
      the rate of stimulation from 0.2 to 0.5 and 1.0 Hz resulted in a negative force
      staircase, the slope of which was identical in control and diabetic animals in
      each [Ca2+]o tested. Postrest contractions and RCC, after variable test
      intervals, were significantly depressed after 0.2 and 0.5 Hz stimulation in
      diabetic muscles at 1.25 mM [Ca2+]o. This defect of SR Ca2+ availability was
      reversed by increasing the stimulation frequency to 1.0 Hz or by elevating
      [Ca2+]o to 2.5 mM. The results suggest that the marked reduction of developed
      tension in diabetic tissues was a consequence of depleted SR Ca2+ stores, rather
      than a result of chronic SR Ca2+ overloading. The maintained integrity of the
      interval-force relation in the presence of diabetes implies that the cellular
      mechanisms responsible for frequency- and time-dependent alterations in SR Ca2+
      availability are not disturbed at this stage of disease.

PMID- 1996681
TI  - Ca2+ sensitivity of isolated arterioles from the hamster cheek pouch.
AB  - When isolated from the hamster cheek pouch, cannulated, and perfused, 60- to 90
      microns arterioles spontaneously contracted to 67 +/- 4% of maximum diameter.
      Vessel sensitivity to variations in extracellular Ca2+ was then evaluated. Tone,
      regardless of its source, was highly dependent on the concentration of Ca2+ in
      the bathing solution. The magnitude of responses to changing Ca2+ depended upon
      which vessel surface (luminal or abluminal) the change was made. For K(+)-induced
      tone the Ca2+ concentration-response curve was right shifted 60-fold for luminal
      vs. abluminal changes. These results suggest that restricted diffusion of Ca2+
      from lumen to smooth muscle dramatically reduces smooth muscle Ca2+ concentration
      and that under standard in vitro conditions the smooth muscle layer is
      effectively isolated from luminal contents. Both the cytosolic and stored Ca2+ in
      these microvessels were dependent on the Ca2+ concentration in the bathing
      solution. Abrupt removal of Ca2+ from bath produced a rapid maximal dilation with
      a mean time to half-maximal response (t1/2 max) of 14 +/- 4 s. Ca2+ replacement
      induced a return to the previous level of tone with a mean t1/2 max of 8 +/- 3 s.
      The magnitude of transient responses to caffeine (10 mM) was inversely related to
      the time of exposure to zero Ca2+ with a rapid decay in magnitude (t1/2 max = 2.7
      +/- 0.8 min). These data suggest that the smooth muscle cells of arterioles have
      a particularly rapid transmembrane Ca2+ flux that is tightly controlled by an
      intracellular regulatory mechanism, which may explain the generally increased
      dependence of smaller vessels on extracellular Ca2+.

PMID- 1996682
TI  - Hypoxia- or hyperoxia-induced changes in arteriolar vasomotion in skeletal muscle
      microcirculation.
AB  - Arteriolar vasomotion was characterized in the skin muscle of the unanesthetized
      hamster skinfold window preparation and related to the specific arterioles that
      give rise to the different types of activity. The arterioles were classified
      according to the Strahler method: order 0 was assigned to capillaries and order 4
      to the largest arterioles. The arterioles showed vasomotion with a specific range
      of frequencies that varied according to the vessel order; the highest fundamental
      frequency (9.1 +/- 3.9 cycles/min) was detected in the smallest order 1
      arterioles and the lowest frequency (2.1 +/- 0.9 cycles/min) in order 4 vessels.
      Hypoxia (8, 11, and 15% O2 gas mixture inspiration) increased the frequency of
      vasomotion, decreased mean and effective diameters, and reduced capillary blood
      flow. The effects were more pronounced with an 8 and 11% O2 gas mixture. Hypoxia
      caused high-frequency vasomotion to shift from order 1 and 2 arterioles to the
      beginning of order 3 arterioles, which in this condition dominated the daughter
      vessels and generated the prominent activity (24 +/- 4 cycles/min, 11% O2 gas
      mixture). Hypertoxia (100% O2) induced differentiated arteriolar responses. The
      smallest vessels showed prolonged constriction, decreased mean and effective
      diameters, and reduced frequency of vasomotion. Capillary blood flow was
      restricted. Order 3 vessels did not constrict or dilate.

PMID- 1996683
TI  - Increased intracellular Na+ and depolarization favor angiotension tachyphylaxis
      in rabbit aorta.
AB  - Tachyphylaxis to both angiotensin II (ANG II) and Sar1-ANG II is observed in
      normal rabbit aorta rings, but helical strips show tachyphylaxis only to Sar1-ANG
      II, whereas everted rings are not tachyphylactic to either analogue. In normal
      rings, a good correlation was observed between intraluminal pH and degree of
      tachyphylaxis to both analogues, suggesting that rate-limiting access of the
      agonists to their site of action may enhance tachyphylaxis in this preparation.
      Membrane potential and intracellular Na+ activity measurements, as well as the
      relaxation by K+ of norepinephrine-contracted preparations in K(+)-free medium,
      indicated that helical strips are more depolarized than everted rings due to Na+
      leakage into the smooth muscle cells. These results suggest that the differences
      in the degree of tachyphylaxis induced by angiotensin in different rabbit aorta
      preparations are due to a less accessible site of action in normal rings and to
      the higher intracellular Na+ and more depolarized state of helical strips
      relative to everted rings.

PMID- 1996684
TI  - Distribution volumes and macromolecular mobility in rat tail tendon interstitium.
AB  - This study explores a centrifugation technique for estimating interstitial fluid
      composition and macromolecular transport. Rat tail tendon supported by a nylon
      net was subjected to three consecutive 15-min centrifugations at 3,000, 6,000,
      and 14,000 revolutions per minute (rpm) or 3, 10, and 20 min at 6,000 rpm.
      Colloid osmotic pressure (COP) and concentrations of albumin, total protein, and
      hyaluronan in subsequent centrifugate fell as exponential functions of
      accumulated centrifuged volume, reaching 10-30% of initial level at an
      accumulated volume corresponding to 8% of tendon volume. Intercepts for zero
      centrifugation were 11 mmHg (COP), 22 mg/ml (albumin), and 39 mg/ml (total
      protein), probably reflecting concentrations in protein-accessible interstitial
      volume. Corresponding serum values were 19 mmHg, 34 mg/ml, and 63 mg/ml. Tendon
      distribution spaces were 0.62 (H2O), 0.57 (51Cr-labeled-EDTA), and 0.22 ml/g wet
      wt (albumin). The progressive fall in centrifugate concentrations probably
      reflects increasing resistance to macromolecular transport, with a sieving
      coefficient for albumin falling from 1 to 0.35, or increasing contribution of
      fluid from protein-excluded space. The effect was reversed by rehydration, which
      caused increased concentrations in centrifugate. Low hyaluronan concentrations in
      centrifugate (0.25 mg/ml) compared with that of whole tendon (0.4 mg/g wet wt)
      reflect either a large "bound" fraction in tissue or marked sieving of hyaluronan
      in normohydration.

PMID- 1996685
TI  - Constrictor action of oxyhemoglobin in monkey and dog basilar arteries in vivo
      and in vitro.
AB  - Angiographic studies on anesthetized dogs and Japanese monkeys showed that
      oxyhemoglobin (HbO2) injected into the cisterna magna produced a constriction of
      the basilar artery; the maximal constriction was attained 2-4 h later.
      Intracisternal injections of autologous blood, prostaglandin (PG) E2 and PGF2
      alpha also constricted the artery to a similar extent, although the peak response
      was obtained much later (approximately 1 wk) with blood and was earlier
      (approximately 20 min) with PGs. The vasoconstrictor action of HbO2 was almost
      abolished by treatment for 5 h with aspirin in dogs and monkeys, whereas
      treatment of dogs with OKY 046, a thromboxane A2 synthesis inhibitor, did not
      significantly alter the action. In isolated monkey basilar arteries, HbO2
      elicited a concentration-related contraction, which was suppressed by treatment
      with aspirin and by endothelium denudation. The basilar arteries responded to
      PGE2 and PGF2 alpha with contractions comparable to those caused by elevated
      external K+. Levels of PGE2, PGF2 alpha, and 6-keto-PGF1 alpha in the nutrient
      solution bathing dog and monkey cerebral arteries were increased by HbO2; the
      increment was depressed by endothelium denudation and by treatment with
      indomethacin. These findings suggest that cerebral artery constriction caused by
      HbO2 in vivo and in vitro is associated mainly with the release of
      vasoconstrictor PGs, such as PGE2 and PGF2 alpha. Endothelium appears to play an
      important role in the release of PGs. Cerebral vasospasm elicited by
      intracisternal injections of HbO2 may be a useful model for the analysis of
      mechanisms underlying the provocation of delayed vasospasm after subarachnoid
      hemorrhage.

PMID- 1996686
TI  - Temporary contractile blockade prevents hypercontracture in anoxic-reoxygenated
      cardiomyocytes.
AB  - Reoxygenation after 120-min substrate-free anoxia causes sudden hypercontracture
      in isolated rat cardiomyocytes. Reoxygenated-hypercontracted cardiomyocytes
      maintain their sarcolemmal integrity as indicated by the absence of enzyme
      release and reestablish a nearly normal free energy change of ATP hydrolysis
      within 15 min [Siegmund, B., A. Koop, T. Klietz, P. Schwartz, and H. M. Piper.Am
      J. Physiol. 258 (Heart Circ. Physiol. 27): H285-H291, 1990]. In the same model,
      it was now investigated whether a temporary contractile blockade by 20 mM 2,3
      butanedione monoxime (BDM) can prevent reoxygenation-induced hypercontracture.
      When BDM was present during 120-min anoxia and the subsequent 15-min
      reoxygenation, hypercontracture could be prevented. The anoxic changes of high
      energy phosphate contents, the free energy change of ATP hydrolysis, and the
      ultrastructure of the cells remained unaffected by the presence of BDM. When BDM
      was applied anoxically immediately before reoxygenation, it also prevented
      hypercontracture. Contracture still remained absent when BDM was washed out after
      the first 15 min of reoxygenation. These results demonstrate that a temporary
      contractile blockade (15 min) at the onset of reoxygenation prevents
      hypercontracture in anoxic-reoxygenated cardiomyocytes. This result, the
      energetic recovery, and the sarcolemmal integrity of cardiomyocytes in anoxia
      reoxygenation demonstrate that reoxygenation-induced hypercontracture is not
      based on an already irreversible cell damage.

PMID- 1996687
TI  - Muscle adaptations in trained rats with peripheral arterial insufficiency.
AB  - The influence of training adaptations, induced within the active muscles of rats
      with peripheral arterial insufficiency, was assessed with an isolated hindlimb
      preparation. Femoral artery-stenosed rats, showing symptoms of intermittent
      claudication, were trained for 14-20 wk by running at 20-35 m/min up a 15% grade
      for up to approximately 1 h/day, 5 days/wk. Similar total hindlimb blood flows
      (12.6 ml/min) at a similar arterial O2 content (20.7 vol/100 ml) yielded similar
      blood flows (95-117 ml.min-1.100 g-1) and O2 deliveries (9-11 mumol.min-1.g-1) to
      the contracting muscle of sedentary (n = 10) and trained (n = 10) rats. Ten
      minute periods of tetanic contractions (100 ms at 100 Hz each) at 4, 8, 13, 45,
      60, and 90 tetani/min were used. Muscle force development was better maintained
      (P less than 0.001) by the trained group. Higher peak O2 consumption (P less than
      0.01) of the trained (5.69 +/- 0.53 mumol.min-1.g-1) compared with the sedentary
      group (3.66 +/- 0.26 mumol.min-1.g-1) involved a greater O2 extraction, since
      delivery of O2 was not different between groups. Thus adaptations occurred within
      trained muscle to enhance performance and peak O2 consumption. Muscle citrate
      synthase activity, an index of mitochondrial content, was greater (P less than
      0.005) in the trained group, with the low-oxidative white muscle section
      exhibiting the greatest change (approximately threefold sedentary). Adaptations
      in this section were probably realized functionally, since improvements in muscle
      performance were evident early in the contraction sequence.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1996688
TI  - Sexual dimorphism in vasopressin-induced contraction of rat aorta.
AB  - Previously, we reported that, in the rat, pressor responsiveness to vasopressin
      (VP) is higher in males than in females during most phases of the estrous cycle.
      To explore the role of the vasculature in this phenomenon, we examined vascular
      reactivity to VP in thoracic aortas of male rats and female rats during each
      phase of the estrous cycle. Aortic rings were prepared from age-matched male and
      female Sprague-Dawley rats and mounted for isometric tension recording. Maximal
      response of female aortas to VP (4,246 +/- 163 mg/mg ring dry wt) was more than
      twice (P less than 0.001) that of male aortas (1,877 +/- 215 mg/mg ring wt).
      Sensitivity of female aortas to VP was substantially higher (P less than 0.001)
      than that of male aortas (EC50: 10.9 +/- 0.7 vs. 19.0 +/- 1.6 nM, respectively).
      Maximal rate of tension development (dT/dtmax) during contraction with VP was
      nearly twofold higher (P less than 0.01) in female aortas (536 +/- 23 mg/min)
      than in male aortas (300 +/- 19 mg/min). Maximal response, sensitivity, and
      dT/dtmax of female aortas did not vary significantly during the estrous cycle.
      Maximal response of female aortas to phenylephrine (PE; 1,251 +/- 93 mg/mg ring
      wt) was half that (P less than 0.001) of male aortas (2,546 +/- 194 mg/mg ring
      wt); sensitivity to PE did not differ significantly (EC50: 0.33 +/- 0.02 vs. 0.38
      +/- 0.06 microM, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1996689
TI  - Characterization of responses of neonatal sinus and AV nodes to critically timed,
      brief vagal stimuli.
AB  - We studied the responses of sinus cycle length and atrioventricular (AV) nodal
      conduction to brief, critically timed vagal stimuli in 25 neonatal (9.6 +/- 3.1
      days) canines. Vagal stimuli were delivered to the right or left decentralized
      cervical vagosympathetic trunk as either a single, brief stimulus train or a
      repetitive, phase-coupled train with both stimulation paradigms programmed to
      scan the entire cardiac cycle. The effects of brief vagal stimuli on cardiac
      cycle length were measured while the heart was beating spontaneously, and the
      vagal effects on AV nodal conduction were measured while the cycle length was
      held constant by atrial pacing at 300 ms. Neither changes in sinus cycle length
      nor AV nodal conduction demonstrated classical phase dependency, i.e., a gradual
      increase in the magnitude of the vagal response as stimuli are delivered
      progressively later in the cardiac cycle until the latency period (that point in
      the cardiac cycle at which vagal stimulation no longer affects the next cardiac
      cycle) is reached. Phase-response curves (PRCs) to single and repetitive stimuli
      typically exhibited either a flat response or a small decrease in magnitude as
      the latency period of the PRC was approached. Thus the neonatal sinus and AV node
      PRCs exhibit a different configuration than that reported in the adult.

PMID- 1996690
TI  - Effects of chronic dobutamine on cardiac mechanics and biochemistry after
      myocardial infarction in rats.
AB  - After myocardial infarction in rats, muscle performance in the remaining
      hypertrophied myocardium deteriorates and is associated with a decrease in myosin
      adenosinetriphosphatase (ATPase) activity and a shift to the V3 myosin heavy
      chain isoform. We have previously shown in another model of hypertrophy,
      secondary to renovascular hypertension, that chronic intermittent adrenergic
      stimulation with dobutamine (Db) can prevent this biochemical adaptation. The
      present study was undertaken to assess the effects of chronic Db treatment on
      cardiac mass, function, metabolism, and myosin biochemistry in animals subjected
      to chronic myocardial infarction. Four groups of rats were studied: controls,
      animals treated with Db (2 mg/kg 2X daily for 4 wk), animals subjected to
      myocardial infarction and killed after 4 wk (MI), and MI animals concurrently
      treated with Db for 4 wk (MI-Db). The two MI groups were subdivided into those
      with and without congestive heart failure (CHF). Heart weight was increased by
      13% with Db, unchanged in the infarct groups without CHF, and increased by 9 and
      22% in the infarct groups with CHF. Db did not have any additional effect on
      heart weight in these later groups. Infarct weight was greatest in the animals
      with CHF, and viable myocardium was equivalent in all infarct groups suggesting
      that CHF was associated with a greater degree of hypertrophy. Ventricular
      performance, as assessed in an isovolumic heart apparatus, was markedly depressed
      in both infarct groups with CHF and was not affected by Db. Db increased myosin
      ATPase activity in control and infarcted animals both with and without congestive
      heart failure. Myosin oxygen consumption and lactate production were not
      adversely affected by Db.

PMID- 1996691
TI  - Nocturnal variations in subcutaneous blood flow rate in lower leg of normal human
      subjects.
AB  - Subcutaneous adipose tissue blood flow rate was measured in the lower leg of 22
      normal human subjects over 12- to 20-h ambulatory conditions. The 133Xe washout
      technique, portable CdTe(Cl) detectors, and a portable data storage unit were
      used. The tracer depot was applied on the medial aspect of the right lower leg 10
      cm proximal to the malleolar level by means of the epicutaneous, atraumatic
      labeling technique. The change from upright to supine position from day 1 in the
      beginning of the night period elicited an instantaneous blood flow rate increment
      of 30-40% in accordance with a decrease in central and local postural sympathetic
      vasoconstrictor activity. During sleep, characteristic variations in subcutaneous
      blood flow were disclosed. The 133Xe washout curve could be divided into three
      segments with significantly different slopes. Approximately 90 min after the
      subject went to sleep, an additional blood flow rate increment of considerable
      magnitude was observed. The mean increase was 84%, but in several cases a greater
      than 200% increment was measured (maximum 244%). The intra-individual coefficient
      of variation for the nocturnal blood flow response was in triplicate measurements
      25% (n = 9). The hyperemic phase lasted approximately 100 min after which the
      blood flow rate returned to the level measured at the beginning of the night
      period. The blood flow rates measured on the second day did not differ from those
      on the first day. Control measurements performed under similar thermal
      conditions, but with the subjects kept awake, did not reveal any hyperemic
      phases. This points toward changes in cardiovascular regulatory mechanisms during
      sleep.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1996692
TI  - Global analysis of myocardial isotonic shortening: comparison with isometric
      dynamics.
AB  - Although potentially analytically useful, a global empirical model of the
      myocardial isotonic curve, L(t), has not been described. We propose the following
      relation: L(t) = C(t/A)B-1e-(t/A)B, where A, B, and C are global parameters, L is
      length, and t is time. We evaluated this model in nine in situ canine papillary
      muscles studied with a servo-system to produce isotonic twitches at different
      isotonic forces (F). For each twitch, the parameters were determined by nonlinear
      curve fitting. The model fit the observed curves of L(t) closely, with the
      coefficient of determination being 0.995 +/- 0.002. C changed with F, but A and B
      varied little with F, averaging 0.262 +/- 0.021 s and 2.76 +/- 0.17,
      respectively. Our predictions that A reflects chronotropic, B reflects
      lusitropic, and C reflects heterotonic (different afterloads) and inotropic
      states were supported. Comparison done in five muscles showed that A was the same
      but B was higher for isotonic than for isometric twitches: 0.270 +/- 0.020 vs.
      0.264 +/- 0.038 s (P = not significant) for A and 2.79 +/- 0.18 vs. 2.39 +/- 0.05
      (P less than 0.008) for B. Dobutamine increased A but not B in isotonic twitches.
      Thus shortening is lusitropic but leaves no lusitropic reserve to be mobilized by
      dobutamine. The relation L(t) = C(t/A)B-1e-(t/A)B provides a framework that
      undergirds global analysis of myocardial shortening and enables comparison with
      isometric dynamics.

PMID- 1996693
TI  - Intracellular free Ca2+ is elevated in hypertrophic aortic muscle from
      hypertensive rats.
AB  - Vessels from hypertensive animals have been shown to have increased medial
      thickness and also to exhibit increased sensitivity to agonists. We tested the
      hypothesis that changes in intracellular Ca2+ concentration [( Ca2+]i) may be
      associated with the growth response and the altered contractility of the aortic
      smooth muscle of modified coarctation-hypertensive rats. Freshly isolated single
      cells, loaded with fura-2, showed significantly higher [Ca2+]i both at rest and
      after depolarization compared with normal rat aortic cells. These cells also
      exhibited at rest a significant nuclear-cytoplasmic [Ca2+] gradient. Furthermore,
      the increased [Ca2+]i was associated with increased nuclear volumes, suggesting
      the presence of polyploid nuclei, as determined by ethidium dimer fluorescence
      imaging. Intact vascular rings from hypertrophic rat aortas, loaded with
      aequorin, also showed significantly higher [Ca2+]i at rest and after
      depolarization compared with normal rat aortas. In addition, the maximal force
      per cross-sectional area generated by the hypertrophic muscle was less than
      normal, consistent with a change in the contractile phenotype of the growing
      smooth muscle cells. This is the first report to directly indicate an increase in
      [Ca2+]i in hypertrophic vascular smooth muscle in hypertensive animals.

PMID- 1996695
TI  - Intracellular PO2 in individual cardiac myocytes in dogs, cats, rabbits, ferrets,
      and rats.
AB  - Myoglobin (Mb) saturation in individual subepicardial myocytes was determined by
      cryospectroscopy in dogs, cats, ferrets, rabbits, and rats. Mb saturation within
      800 microns of the epicardium is not affected by quick freezing or absorption of
      light by cytochromes. The PO2 in equilibrium with Mb (PMbO2) was calculated from
      the Mb oxydissociation curve. The minimum PMbO2 found among the 1,000 cells
      examined was 2.5 Torr, at least five times the critical PO2 for cytochrome
      turnover in myocardium. The maximum PMbO2 found was about one-half that in
      subepicardial venules, suggesting a large change in PO2 between capillaries and
      the cytosol. PMbO2 was the same in right and left ventricles and was unchanged by
      moderate hemodynamic stress. Median PMbO2 was remarkably uniform among species
      (range, 4.3-7.0 Torr in 20 animals), even though left ventricular work per minute
      varied approximately 200-fold, heart rate about fivefold, and arterial O2 content
      about twofold. Relatively uniform Mb saturation below venous PO2 should
      accelerate release of O2 from capillaries, promote Mb-facilitated O2 diffusion,
      and minimize diffusive O2 shunting.

PMID- 1996694
TI  - Myocardial metabolic effects of in vivo hydralazine treatment of streptozotocin
      diabetic rats.
AB  - We determined myocardial pumping capacity, glucose oxidation, and mechanical
      response to ischemia in streptozotocin-diabetic rats treated for 4 wk with or
      without hydralazine (0.5 mg/g of chow). Plasma triglycerides and cholesterol were
      decreased 73 and 50%, respectively, in the treated animals. Blood glucose levels
      were greater than 400 mg/100 g in both groups. Hearts were perfused in the
      working configuration with buffer containing 5 mM [U-14C]glucose. Starling curves
      were constructed by increasing left atrial filling pressure from 5 to 20 cm of
      water. Diabetic heart mechanical function was depressed compared with control and
      hydralazine treatment restored function to normal. Oxidation of [U-14C]glucose
      was comparably depressed in the treated and untreated diabetics. The provision of
      1 mM dichloroacetate in the perfusate increased glucose oxidation in the hearts
      from hydralazine-treated rats, however. Twenty minutes of global ischemia
      resulted in 65% decrease in mechanical function in the hearts of hydralazine
      treated group vs. 15% for hearts from nontreated diabetics. The data suggest that
      measures to normalize lipid metabolism may not normalize myocardial glucose
      oxidation or permit better mechanical recovery after ischemia in the diabetic
      myocardium.

PMID- 1996696
TI  - Dependence of cerebral energy phosphate and evoked potential recovery on end
      ischemic pH.
AB  - We determined whether the rate of metabolic recovery and electrophysiological
      deficit after incomplete cerebral ischemia is related to intracellular pH (pHi)
      achieved at the end of ischemia in a dose-dependent manner. End-ischemic pHi was
      varied by employing two ischemic durations, 12 and 30 min, and by setting
      preischemic plasma glucose to approximately 80 or 400 mg/dl. Incomplete global
      ischemia was produced in anesthetized dogs by transient intracranial hypertension
      followed by 4 h of reperfusion, and pHi, ATP, and phosphocreatine (PCr) were
      measured with 31P magnetic resonance spectroscopy. Cerebral blood flow was
      reduced to approximately 6 ml.min-1.100 g-1 during ischemia. End-ischemic pHi was
      greater than 5.7 in all animals from various treatment groups except for four of
      seven dogs treated with 30-min hyperglycemic ischemia. When end-ischemic pHi
      remained greater than 5.7, there was nearly complete recovery of ATP, PCr, pHi,
      intracellular bicarbonate concentration [( HCO3-]i), and O2 consumption. Partial
      recovery of somatosensory-evoked potentials (SEP) occurred in most of these
      animals. In the 30-min hyperglycemic animals in which pHi fell below 5.5, ATP,
      PCr, and O2 consumption recovered by only one-half over 60 min of reperfusion and
      then declined to near-zero levels without SEP recovery. In addition, pHi remained
      less than 6.0, and [HCO3-]i remained less than 2 mM throughout reperfusion. We
      conclude that there is an apparent in vivo pHi threshold of approximately 5.5-5.7
      during incomplete cerebral ischemia that is associated with an inability to
      significantly restore pHi and [HCO3-]i and with secondary deterioration of high
      energy phosphate levels.

PMID- 1996698
TI  - Oxidative stress inhibits bradykinin-stimulated 45Ca2+ flux in pulmonary vascular
      endothelial cells.
AB  - The effects of oxidant stress and altered glutathione reductase activity on
      agonist-induced flux of Ca2+ were studied in cultured calf pulmonary artery
      endothelial cells using radioisotopic 45Ca2+. Bradykinin-stimulated uptake of
      45Ca2+ was determined after cells were incubated with the membrane-permeant
      oxidant t-butylhydroperoxide (0.4 mM) for various durations. t-Butylhydroperoxide
      increased uptake of 45Ca2+ under basal conditions and significantly decreased
      bradykinin-stimulated uptake in a time-dependent manner through incubation
      periods of 2 h. Preincubation of cells with 1,3-bis(chloroethyl)-1-nitrosourea
      markedly reduced bradykinin-stimulated uptake in cells subsequently treated with
      t-butylhydroperoxide. Bradykinin-stimulated efflux of 45Ca2+ and 86Rb+ was
      examined in control and oxidant-stressed endothelial cells. t-Butylhydroperoxide
      initially decreased bradykinin-stimulated efflux of 45Ca2+ but had no effect on
      86Rb+ efflux. After more prolonged incubation with the oxidant, stimulated 45Ca2+
      efflux was further inhibited, and basal efflux of 86Rb+ was increased to a rate
      similar to that observed with bradykinin stimulation. Elevated basal 86Rb+ efflux
      was blocked by tetrabutylammonium chloride, a selective inhibitor of Ca2(+)
      dependent K+ channels in endothelial cells. These findings, together with our
      previously described results using fura-2, suggest that oxidant stress initially
      inhibits bradykinin-stimulated Ca2+ influx and later inhibits stimulated Ca2+
      efflux. Finally, cytosolic free Ca2+ concentration becomes persistently elevated
      and is associated with elevated basal efflux of K+ via the Ca2(+)-dependent K+
      channel.

PMID- 1996697
TI  - Feeding and fasting determine postischemic glucose utilization in isolated
      working rat hearts.
AB  - To assess the effects of endogenous substrate on glucose utilization after 15 min
      of ischemia, we perfused isolated working rat hearts from fed and fasted (16 h)
      animals with glucose and the positron-emitting glucose analogue 2-[18F]fluoro-2
      deoxy-D-glucose (2-FDG). Hearts were perfused in a recirculating system with
      bicarbonate buffer containing glucose (10 mM) and 2-FDG (0.5 microCi/ml).
      Mechanical performance and 2-FDG uptake were measured on-line, and glucose and
      lactate metabolic rates were calculated. Fasting raised the glycogen content by
      25% and the triglyceride content by 38%. Hearts in both groups recovered
      preischemic function. Rates of 2-FDG uptake during the preischemic period were
      the same in both groups. In contrast, during the postischemic period rates of 2
      FDG uptake were significantly depressed in hearts of fed animals but were
      unchanged in hearts of fasted animals. Thus hearts of fasted animals took up more
      2-FDG during the postischemic period than hearts of fed animals (P less than
      0.005). The lumped constant (range, 0.38-0.40) was the same in both groups before
      and after ischemia. Glucose utilization was suppressed during the postischemic
      period in hearts of fed animals, whereas at the same time lactate utilization was
      significantly increased. We conclude that 1) 2-FDG accurately traces glucose
      utilization independent of the nutritional state or ischemic insult; 2)
      reversibly ischemic, viable myocardium exhibits vastly different rates of glucose
      utilization depending on the nutritional state of the animal before ischemia; 3)
      lactate derived from glycolysis suppresses utilization of exogenously supplied
      glucose in the early reperfusion period without affecting postischemic
      performance.

PMID- 1996700
TI  - Contractile strength and mechanical efficiency of left ventricle are enhanced by
      physiological afterload.
AB  - Recent studies have shown that at the same endsystolic volume, ejecting beats can
      achieve a higher end-systolic pressure than isovolumic beats. The purpose of this
      study was to assess the metabolic cost, in terms of oxygen consumption (MVO2),
      and efficiency, in terms of the relation between MVO2 and pressure-volume area
      (PVA), of this increase in strength during ejection. The slope of the end
      systolic pressure-volume relation (ESPVR) (Ees) was greater during ejecting than
      isovolumic contractions when ejection fraction (EF) was greater than
      approximately 30%, indicating an increase in contractile strength. The difference
      in Ees between the two modes of contraction was as much as 30% at EFs of 60%. In
      contrast, the slope of the MVO2-PVA relation was less during ejecting than
      isovolumic contractions, indicating a decrease in MVO2 at any given PVA. The
      difference in slope was as much as 20% at EFs of 60%. Thus afterload conditions,
      allowing substantial fiber shortening, shift the ESPVR toward greater contractile
      strength and increase the metabolic efficiency when viewed in terms of the
      relation between MVO2 and total mechanical energy generation (PVA) by the
      ventricle. This may reflect an energetically favorable effect of shortening on
      muscle force-generating capability.

PMID- 1996699
TI  - Xanthine oxidase is not a major source of free radicals in focal cerebral
      ischemia.
AB  - Xanthine oxidase (XO) has been proposed as an important source of free radicals
      during ischemia. This enzyme normally exists as a dehydrogenase (XD), but it is
      converted to XO in some ischemic tissues. Recently, treatment of animals with the
      XD and XO inhibitor allopurinol or with free radical scavengers before cerebral
      ischemia has been shown to reduce brain injury. Therefore, we studied conversion
      of XD to XO in three ischemic and nonischemic brain regions during focal cerebral
      ischemia resulting from permanent occlusion of the middle cerebral artery (MCAO)
      in anesthetized rats. In nonischemic brain, 16-22% of the enzyme was in the XO
      form. After 24 h of ischemia this value was not significantly different (10-15%).
      Neither the total activity of XO nor that of XD changed, indicating that there
      was no irreversible conversion of XD to XO. To further explore the possible role
      of XO, we examined the effect of various doses of allopurinol (5, 20, or 100
      mg/kg given 1 h before MCAO or 100 mg/kg given 48, 24, and 1 h before MCAO) on
      uric acid accumulation, brain edema formation, and cerebral blood flow (CBF) 24 h
      after MCAO. All but the lowest dose of allopurinol greatly reduced the appearance
      of uric acid in the ischemic brain; however, only the highest dose of allopurinol
      had any beneficial effect on brain edema. This reduction in brain edema occurred
      without a significant improvement in CBF. Thus XO is probably not an important
      source of free radicals in this model of focal cerebral ischemia.

PMID- 1996701
TI  - Capillary spatial pattern and muscle fiber geometry in three hamster striated
      muscles.
AB  - Since most oxygen exchange in muscle is thought to occur by diffusion across the
      walls of capillaries, it is important to determine the spatial relationship
      between capillaries and muscle fibers. We have extended the work of Kayar et al.
      (Microvasc. Res 24: 326-341, 1982) to include other statistical tests that allow
      one to make stronger statements regarding the spatial pattern. Data for hamsters
      were obtained from two sartorius, three retractor, and five soleus muscle
      sections. Distances between all pairs of capillaries, distances between a
      capillary and its first nearest neighbor for all capillaries, and distances
      between random tissue sample points and the closest capillary were used to test
      the spatial arrangement of capillaries. The null hypothesis tested of complete
      spatial randomness of capillary locations was rejected in favor of a regular
      alternative in one each of the sartorius and retractor fields and in all five
      soleus fields. We formulated a geometric model, composed of a space-filling array
      of identical hexagonal muscle fibers with capillaries placed randomly at the
      juncture of three fibers or between two fibers, according to the observed
      relative probability of those occurrences. The model simulations of muscle fibers
      and capillaries were then analyzed by the same statistical tests used on the
      histological sections. The findings were similar in both cases, providing
      confidence that the assumptions of the model were sufficient approximations. The
      results of this study provide a basis for the placement of capillaries around
      muscle fibers in mathematical models of oxygen transport in capillary networks.

PMID- 1996702
TI  - Sensitivity of myocardial fluorodeoxyglucose lumped constant to glucose and
      insulin.
AB  - The lumped constant (LC) that relates the steady-state phosphorylation rate of 2
      [18F]-fluoro-2-deoxy-D-glucose (2-FDG) to that of glucose was determined in an
      isolated working rat heart model by direct assay of phosphorylation product
      formation. Five conditions were tested: 5 and 30 mM glucose without insulin, and
      2, 3.5, and 5 mM glucose + 10 mU/ml insulin, all at high external work load.
      Hearts were continuously perfused with 2-FDG and tritiated glucose without
      recirculation. The steady-state production of tritiated water was used to monitor
      the glucose phosphorylation rate. Perfused hearts were freeze-clamped and
      extracted in perchloric acid, and 2-FDG-6-phosphate was separated from 2-FDG with
      a formate column. The accumulation of 2-FDG phosphorylation products in tissue
      was also determined from the slopes of the total tissue radioactivity time
      courses measured by external gamma-ray detection. Without insulin, the LC value
      decreased 18% as perfusate glucose concentration was increased sixfold (0.94 +/-
      0.06 at 5 mM vs. 0.77 +/- 0.17 at 30 mM). With insulin, the LC rose from 0.33 +/-
      0.03 at 5 mM to 1.19 +/- 0.05 at 2 mM glucose concentration. The trends can be
      interpreted in terms of the concept of control strength; the LC value rises as
      glycolysis becomes rate limited by transport into cells. This potential
      variability of the LC must be addressed in the quantitative interpretation of
      myocardial deoxyglucose studies.

PMID- 1996703
TI  - Vasopressin stimulates the mobilization and metabolism of triacylglycerol in
      perfused rabbit hearts.
AB  - Vasopressin stimulates several metabolic processes, including glycogenolysis,
      gluconeogenesis, and fatty acid oxidation, and promotes lipolysis in rabbit and
      hamster suprarenal adipose tissue. This study was conducted to determine whether
      arginine vasopressin (AVP) stimulates the metabolism of triacylglycerols in the
      isolated perfused rabbit heart. Since the basal output of glycerol in the rabbit
      heart is very low, the triacylglycerol pool was labeled with [3H]triolein, and
      triacylglycerol metabolism was followed by analysis of the radioactive products
      in the perfusate. Administration of AVP (100 ng, 92 pmol) produced a 10-fold
      increase in the perfusate radioactivity associated with free fatty acids and mono
      and diglycerides, as well as an 8-fold increase in the effluent radioactivity
      associated with triacylglycerol. The V1-receptor antagonist d[(CH2)5Tyr(Me)]AVP
      blocked the AVP-induced increase in the output of radioactivity in a dose-related
      manner. The V2-receptor agonist desmopressin (DDAVP) did not increase the outflow
      of radioactivity. Likewise, AVP-induced release of radioactivity was inhibited
      when Ca2+ was omitted from the perfusion buffer. Analysis of total lipid extracts
      of hearts labeled with [3H]triolein showed that the residual radioactivity was
      associated almost exclusively with authentic triolein both before and after AVP
      treatment. These data suggest that AVP promotes triacylglycerol mobilization and
      utilization and that these processes are Ca2+ dependent and mediated by the V1
      receptor. Since free fatty acids derived from triacylglycerols are the preferred
      metabolic substrate for the heart and since plasma AVP levels increase in cardiac
      stress states such as shock, these findings suggest a metabolic function of AVP
      in cardiovascular stress states.

PMID- 1996704
TI  - Response time of cardiac mitochondrial oxygen consumption to heart rate steps.
AB  - We investigated the time course of cardiac mitochondrial O2 consumption following
      steps in heart rate in 16 isolated rabbit hearts perfused with Tyrode solution.
      The time course was characterized by the mean response time, i.e., the first
      statistical moment (mean time) of the impulse response function. Like the mean
      transit time for an indicator, it provides an important characteristic of the
      response time course. The venous O2 content transients during steps in heart rate
      were measured and corrected for O2 diffusion and vascular transport using a
      mathematical model with experimental information derived from O2 washout
      following steps in arterial O2 concentration or perfusion flow. We deduce from
      these washout experiments that the effective O2 solubility in heart tissue is 86
      +/- 13% (mean +/- SE) of solubility in water. The measured venous mean response
      time following a step in heart rate at 37 degrees C was 17.6 +/- 1.1 s. The mean
      response time of cardiac mitochondrial O2 consumption to changes in heart rate
      after correction for O2 transport was 7.7 +/- 0.7 s.

PMID- 1996705
TI  - Oxy- and carboxyhemoglobin saturation determination in frozen small vessels.
AB  - A four-wavelength microspectrophotometric method has been developed to determine
      both O2 and CO saturation of hemoglobin in frozen small vessels. This method
      compensates for the nonspecific light loss related to the ice crystals and in
      addition can simultaneously measure both hemoglobin O2 and CO saturation in
      frozen blood. By using four wavelengths in the 540-580 nm range, it is possible
      to determine both O2 and CO saturations in frozen blood. This four-wavelength
      method demonstrated an accuracy of 6-8% within 95% confidence limits (SE of
      estimate = 3-4%) for both CO and O2 saturation determinations in frozen blood.
      The linear regression of the hemoglobin O2 saturation calibration was significant
      with an r2 value of 0.989. The linear regression of the CO saturation calibration
      was also significant with an r2 of 0.996. The repeatability of each measurement
      was on the order of 1-6%. This method also represents an accuracy within 5% for
      measurements in the frozen rabbit heart for both CO and O2 in vessels between 20
      and 100 microns in diameter. It compares favorably with other previously reported
      methods. It shows a similar accuracy but requires fewer repeat measurements than
      the three-wavelength method. This method can provide accurate measurement of O2
      and CO saturation in small frozen arterioles and venules of any organ.

PMID- 1996706
TI  - Regional vascular resistance vs. conductance: which index for baroreflex
      responses?
AB  - When large changes in baseline blood flow occur in regional vascular beds (i.e.,
      in skeletal muscle between rest and dynamic exercise or in skin between
      normothermia and hyperthermia) opposite conclusions are often drawn regarding the
      magnitude of a given vasomotor response (such as baroreflex vasoconstriction
      during hypotension) using regional resistance versus conductance. This report
      analyzes the relationship between changes in regional resistance or conductance
      and the contribution of the responses in the maintenance of blood pressure. The
      main supposition is that the appropriate index of baroreflex responses should
      reflect the importance of the response in the maintenance of blood pressure.
      Through differential analysis of the relationship between changes in resistance
      and conductance on arterial pressure, it can be seen that in terms of resistance,
      the effect of a given change in resistance on arterial pressure is greatly
      dependent on the baseline level of resistance. For conductance, while a modest
      baseline effect exists when cardiac output changes markedly, at a constant
      cardiac output, the same change in regional conductance always causes the same
      change in arterial pressure regardless of the initial value of conductance.
      Conclusions drawn are that while neither resistance nor conductance is a perfect
      index of vasomotor responses, changes in conductance far better reflect the
      importance of the response in pressure regulation than do changes in regional
      resistance.

PMID- 1996707
TI  - Acute, reversible tricuspid insufficiency: creation in canine model.
AB  - Relatively few methods have been described for the creation of valvular
      insufficiency in an animal model. Those presented involve limitations such as
      permanent destruction of the valves or lack of control over the degree of
      regurgitation produced. We describe a method of acute reversible tricuspid
      insufficiency that can be easily created and controlled in anesthetized dogs. The
      model employs a wire spiral that is advanced through the atrioventricular canal
      from the right atrium. The spiral causes regurgitation by preventing complete
      apposition of the valve leaflets while permitting retrograde flow to occur
      through the spiral lumen. The degree of regurgitation can be controlled by the
      use of spirals of different sizes. Creation of tricuspid insufficiency is
      demonstrated by the onset of right atrial pressure V waves, a "ballooning" of the
      right atrium during ventricular systole, palpation of an atrial thrill, or by
      color Doppler echocardiography. In 14 dogs, right atrial pressure increased from
      a control value of 9 +/- 3 (mean +/- SD) mmHg to 10 +/- 3 and 12 +/- 3 mmHg,
      respectively, with spirals of 1.5 and 2.2 cm in diameter (both P less than 0.05).
      With the 2.2-cm spiral, aortic blood pressure decreased from a control value of
      104 +/- 20 to 83 +/- 17 mmHg (P less than 0.05), and cardiac output decreased
      from 73 +/- 26 to 59 +/- 19 ml.min-1.kg-1 (P less than 0.05). This model is
      reversible, allows repeated trials of various grades of regurgitation, does not
      require ventriculotomy, and is relatively nonarrhythmogenic.

PMID- 1996708
TI  - Shear stress increases endothelial platelet-derived growth factor mRNA levels.
AB  - We have investigated the effect of shear stress on platelet-derived growth factor
      (PDGF) A and B chain mRNA levels in cultured human umbilical vein endothelial
      cells (hUVEC). The levels of both PDGF A and B mRNA in hUVEC were increased by a
      physiological shear stress (16 dyn/cm2), reaching a maximum approximately 1.5-2 h
      after the onset of shear stress and returning almost to control values at 4 h.
      The peak levels showed a more than 10-fold enhancement for PDGF A mRNA and a 2-
      to 3-fold increase for PDGF B mRNA (P less than 0.05). PDGF A mRNA also showed a
      shear-dependent increase from 0 to 6 dyn/cm2 (P less than 0.05) and then
      plateaued from 6 to 51 dyn/cm2. PDGF B mRNA levels were elevated as shear stress
      increased from 0 to 6 dyn/cm2 then declined gradually to a minimum at 31 dyn/cm2
      (P less than 0.05) and increased again when shear stress rose to 51 dyn/cm2 (P
      less than 0.05). PDGF, a potent smooth muscle cell mitogen and vasoconstrictor,
      released from the endothelium may regulate the blood flow in vivo. The shear
      stress-dependent elevation of PDGF A and B mRNA in endothelial cells may be
      involved in the adaptation of blood vessels to flow mediated by the endothelium.

PMID- 1996709
TI  - Alterations in cardiac parasympathetic function in aged rats.
AB  - Aging impairs sympathetic and parasympathetic cardiac control. Although the
      reduced sympathetic responses are known to depend on an age-related cardiac beta
      adrenoceptor dysfunction, the hypothesis of a parallel cardiac muscarinic
      receptor dysfunction underlying the reduced parasympathetic responses has never
      been tested. We therefore measured the bradycardic responses to graded electrical
      stimulations of the right efferent vagus and to graded bolus intravenous
      injections of acetylcholine in anesthetized, vagotomized rats of young (16 wk)
      and old (103 wk) age. Unexpectedly, the bradycardia was markedly larger (greater
      than 2-fold) in old than in young rats with both the electrical and the
      pharmacological stimulus. This indicates that at variance with its effects on
      beta-adrenergic receptor responsiveness, aging not only fails to impair but
      actually enhances cardiac muscarinic receptor responsiveness. It also suggests
      the more general conclusion that aging has complex and diversified effects rather
      than simply and uniformly depressing biological functions.

PMID- 1996711
TI  - Capsaicin attenuates bombesin-induced suppression of food intake.
AB  - This study was conducted to evaluate the extent to which bombesin (BBS)-induced
      suppression of food intake relies on small, unmyelinated sensory neurons. Rats
      were pretreated intraperitoneally with capsaicin, a neurotoxin that destroys a
      subpopulation of small-diameter sensory neurons, and tested for suppression of
      food intake after intraperitoneal administration of 2, 4, 8, 16, and 32
      micrograms/kg BBS. Capsaicin pretreatment attenuated suppression of food intake
      by BBS over a wide range of doses. The site of capsaicin action was not
      determined in this study. However, work by others indicates that vagal and
      nonvagal neural substrates participate in suppression of food intake by BBS.
      Afferents of both of these substrates are predominantly small and unmyelinated.
      Therefore, the deficits in BBS-induced suppression of food intake that we
      observed may reflect damage to both vagal and/or nonvagal neurons that
      participate in BBS-induced suppression of food intake.

PMID- 1996710
TI  - Branched-chain amino acids augment neither albuminuria nor albumin synthesis in
      nephrotic rats.
AB  - Both albuminuria (UalbV) and albumin synthesis (AlbSyn) are modulated by dietary
      protein in nephrotic rats, but the agent(s) linking diet to altered UalbV and
      AlbSyn is unknown. Others have reported that branched-chain amino acids (BCAA)
      cause neither increased renal blood flow nor glomerular filtration rate (GFR)
      normally induced by dietary protein nor increased blood glucagon thought to be
      necessary for protein-mediated effects on renal hemodynamics. The effect of BCAA
      on UalbV is unknown. Because BCAA increase AlbSyn in tissue culture and after a
      fast, it is possible that feeding BCAA may increase AlbSyn but not UalbV in
      nephrosis. Nephrotic rats were fed either 8.5% casein (LP); 21% casein (NP); 8.5%
      casein supplemented with valine, leucine, and isoleucine to the total amount
      provided by a 21% casein diet (2.37%) (LBC); or 8.5% casein plus 12.5% BCAA
      providing a diet isonitrogenous to 21% casein (HBC). UalbV and AlbSyn were
      significantly greater in NP compared with LP, LBC, or HBC and were the same in
      the latter three groups. Glucagon was infused into nephrotic rats fed 8.5% casein
      either subcutaneously or intraperitoneally in quantities sufficient to increase
      plasma levels to over 10 times control but had no effect on UalbV. The ability of
      dietary protein to increase AlbSyn or UalbV is not a result of total alpha-amino
      nitrogen intake but is a result of the specific amino acid composition of the
      diet and must result entirely from the effect of one or more non-BCAA. Increased
      blood glucagon alone has no effect on UalbV.

PMID- 1996712
TI  - Adaptations to prolonged fasting in free-living weaned gray seal pups.
AB  - The water and energy metabolism of 12 free-living gray seal pups during their
      postweaning fast was investigated using tritiated water for determination of
      rates of energy expenditure and water turnover and changes in body composition.
      Changes in serum composition and urinary output were also measured. The duration
      of the postweaning fast ranged from 10 to greater than 28 days. The mean daily
      energy expenditure of pups was 12.0 +/- 1.0 (SE) MJ, equivalent to 2.7 times the
      basal metabolic rate predicted from M. Kleiber (The Fire of Life. Huntington, NY:
      Krieger, 1975). On average, lipid catabolism provided 94% of the energy used.
      Water-turnover rates were lower than predicted from C. R. Richmond, W. H.
      Langham, and T. T. Trujillo (J. Cell. Comp. Physiol. 59: 45-55, 1962). Urinary
      output of water and solute were also low, and these declined as the fast
      progressed. Although pups were in negative water balance, there was no evidence
      that they experience dehydration during the post-weaning fast. The principal
      adaptations to prolonged fasting in weaned gray seals are, therefore, lowering of
      field metabolic and water-turnover rate and reliance on stored lipid as fuel.

PMID- 1996713
TI  - Elevated central venous pressure: a consequence of exercise training-induced
      hypervolemia?
AB  - Resting blood volumes and arterial and central venous pressures (CVP) were
      measured in 14 men before and after exercise training to determine whether
      training-induced hypervolemia is accompanied by a change in total vascular
      capacitance. In addition, resting levels of plasma arginine vasopressin (AVP),
      atrial natriuretic peptide (ANP), aldosterone (Ald), and norepinephrine (NE) were
      measured. The same measurements were conducted in seven subjects who did not
      undergo exercise and acted as controls. Exercise training consisted of 10 wk of
      controlled cycle exercise for 30 min/day, 4 days/wk at 75-80% of maximal O2
      uptake (VO2max). A training effect was verified by a 20% increase in VO2max, a
      resting bradycardia, and a 9% increase in blood volume. Mean arterial blood
      pressure was unaltered by exercise training, but resting CVP increased by 16% (P
      less than 0.05). The percent change in blood volume from before to after training
      was linearly related to the percent change in CVP (r = 0.903, P less than 0.05).
      As a consequence of elevations in both blood volume and CVP, the volume-to
      pressure ratio was unchanged after exercise training. Plasma AVP, ANP, Ald, and
      NE were unaltered. Our results indicate that elevated CVP is a consequence of
      training-induced hypervolemia without alteration in total effective venous
      capacitance.

PMID- 1996714
TI  - Effects of a peroxisome proliferator on beta-oxidation and overall energy balance
      in obese (fa/fa) rats.
AB  - The aim of the study was to examine in the obese Zucker (fa/fa) rats the effect
      of a peroxisome proliferator nafenopin on liver and brown adipose tissue
      peroxisomal and mitochondrial beta-oxidation enzyme activities and on the overall
      energy dissipation. A 17-day nafenopin treatment increased liver wet weight 2.1
      fold and liver total acyl-CoA oxidase and mitochondria beta-oxidative activities
      32- and 4.6-fold, respectively. It increased the interscapular brown adipose
      tissue (IBAT) acyl-CoA oxidase activity 2.1-fold but had no effect on the
      mitochondria beta-oxidative activity. Because nafenopin was found to decrease
      food intake by 22%, obese nafenopin-treated rats were compared with a group of
      obese pair-fed rats. Both food restriction and nafenopin treatment decreased body
      weight gain, but a decrease (14%) in fat content was only observed in nafenopin
      treated rats. Food restriction of obese rats decreased the mean metabolic rate by
      13%, and nafenopin treatment prevented this decrease. Both food restriction and
      nafenopin treatment decreased the mean daily respiratory quotient (RQ). However,
      the RQ of nafenopin-treated rats was steadily lower than that of control, whereas
      that of food-restricted rats was the same as that of control animals during the
      feeding period and decreased when food supply was exhausted. The increase in
      liver and IBAT fatty acid beta-oxidative activities may be the cause of the
      decreased lipid accretion measured in obese rats.

PMID- 1996716
TI  - Sympatholytic response to stimulation of superior laryngeal nerve in rats.
AB  - The central pathway mediating a sympatholytic response to stimulation of the
      superior laryngeal nerve (SLN) was studied in halothane-anesthetized, paralyzed
      rats. Single-pulse stimulation of SLN inhibited lumbar sympathetic nerve
      discharge (LSND) with onset latency of 113 +/- 1.7 ms. LSND inhibition was
      markedly attenuated by bilateral microinjection of kynurenic acid (Kyn, glutamate
      receptor antagonist, 4.5 nmol/side) into the caudal ventrolateral medulla (CVL)
      or by bilateral administration of bicuculline methiodide (Bic; gamma-aminobutyric
      acid-receptor antagonist, 225 pmol/side) into the rostral ventrolateral medulla
      (RVL). In 13 of 14 cases, the baroreceptor reflex was also severely reduced.
      Injections of Bic or Kyn elsewhere in the medullary reticular formation were
      ineffective. Single-pulse stimulation of SLN inhibited 19 of 26 RVL
      reticulospinal barosensitive cells (onset latency 46 +/- 1.4 ms). This inhibition
      was attenuated (from 92 +/- 6 to 14 +/- 12%) by iontophoretic application of Bic
      (n = 7), which also reduced the cells' inhibitory response to aortic coarctation.
      The remaining seven barosensitive neurons were unaffected by SLN stimulation. In
      conclusion, the sympathetic baroreflex and the sympathoinhibitory response to SLN
      stimulation appear to be mediated by similar medullary pathways.

PMID- 1996715
TI  - Effect of age on cold acclimation in rats: metabolic and behavioral responses.
AB  - To determine whether senescence affects the metabolic and behavioral responses of
      rats to chronic cold exposure, 8- and 22-mo-old male Fischer 344 rats were
      studied before and after 6 wk of cold (6-10 degrees C) exposure. Measurements of
      body weight, food consumption, oxygen consumption, body temperature, and ambient
      temperature selection in a thermocline (7-37 degrees C linear gradient) were made
      at regular intervals throughout the acclimation period. Before acclimation, age
      groups differed significantly only by weight. During acclimation, older rats had
      increased mortality and morbidity below 10 degrees C. After acclimation at 10
      degrees C, younger and older rats both selected cooler ambient temperatures (7
      and 5 degrees C cooler than preacclimation, respectively), and older rats had a
      significantly greater decrease in body temperature in the thermocline. Both age
      groups increased resting metabolic rate at 25 degrees C with cold acclimation
      (16.5 and 10% increase for younger and older rats, respectively). This study
      indicates distinct differences in metabolic and behavioral responses of younger
      and older rats to cold acclimation. Chronic cold exposure is detrimental to
      thermoregulatory function in older rats, since it is not as effective in
      stimulating sustained increases in metabolic rate in older rats as in young
      adults and it leads to a preference for cooler ambient temperatures, resulting in
      increased heat loss and reduced body temperature.

PMID- 1996717
TI  - Role of renal nerves in sodium retention of cirrhosis and congestive heart
      failure.
AB  - To define the role of renal nerves in renal Na retention of cirrhosis and
      congestive heart failure (CHF), experiments were done in rats with cirrhosis due
      to common bile duct ligation (CBDL) and CHF due to myocardial infarction from
      left coronary artery ligation. Two weeks after induction of CBDL or CHF, diseased
      and sham diseased (Sham) rats were subjected to bilateral renal denervation (DNX)
      or sham renal denervation (innervated, INN). Five days after DNX or INN, 26-day
      metabolic balance studies were carried out in all rats. Daily dietary Na intake
      averaged 2.0-3.0 meq/day on days 1-6 and 22-26 and averaged 0.120 meq/day on days
      7-21. Cumulative Na balance was greater in CBDL and CHF rats, INN or DNX, than in
      Sham/CBDL or CHF rats throughout the study. On day 6 at the end of the normal
      dietary Na intake period (days 0-6), cumulative Na balance was not affected by
      renal denervation in Sham/CBDL or CHF rats (INN, 2.02 +/- 0.19 meq, n = 10; DNX,
      2.04 +/- 0.17 meq, n = 11), CBDL rats (INN, 4.21 +/- 0.39 meq, n = 10; DNX, 3.78
      +/- 0.37 meq, n = 10), or CHF rats (INN, 3.74 +/- 0.72 meq, n = 9; DNX, 3.22 +/-
      0.55 meq, n = 10).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1996719
TI  - Effects of intracerebroventricular injection of neuropeptide Y on energy
      metabolism.
AB  - Our objective was to find out if central injection of neuropeptide Y (NPY) would
      alter brown fat thermogenesis and white fat lipoprotein lipase activity. The
      following three groups of Sprague-Dawley rats received five injections over 24 h
      into the right lateral ventricle: 1) NPY (5 micrograms/injection) and ad libitum
      food; 2) NPY (5 micrograms/injection) and food restricted to control intake; 3)
      saline injection and ad libitum food. The NPY ad libitum-fed group consumed more
      food than the saline controls or NPY food-restricted animals. Brown fat
      thermogenic activity, assessed by GDP binding, was decreased relative to saline
      controls in both NPY-treated groups. White fat lipoprotein lipase activity was
      greatly increased in both NPY treatment groups compared with saline controls. The
      NPY effects on brown and white fat were not explained by measures of serum
      insulin, glucagon, glucose, or other metabolites. In a follow-up experiment, we
      asked whether food was necessary for expression of the NPY effects. Brown fat
      mitochondrial GDP binding indicated NPY effect even when no food was ingested. We
      conclude that intracerebroventricular administration of NPY promotes white fat
      lipid storage and decreases brown fat thermogenesis in addition to its known
      effect of stimulating food intake.

PMID- 1996718
TI  - Simultaneous evaluation of medullary secretory functions of normal and acutely
      denervated adrenals.
AB  - Adrenal medullary secretory function of the right innervated gland was
      simultaneously compared with that of contralateral acutely denervated gland in
      anesthetized dogs. During bilateral carotid artery occlusion (BCO), output (in
      ng/min) from right innervated gland of epinephrine and norepinephrine increased
      from 86.6 +/- 33.0 and 34.4 +/- 15.1 to 280.8 +/- 86.7 (P less than 0.01, n = 7)
      and 104.4 +/- 40.6 (P less than 0.01, n = 7), respectively. By contrast,
      epinephrine output from left denervated gland increased only slightly (P less
      than 0.05), and norepinephrine did not increase significantly. Net catecholamine
      output from left denervated gland was markedly attenuated by approximately 90% (P
      less than 0.01, n = 7) compared with that from right innervated gland. During BCO
      in the second group of dogs, catecholamine output from sham-denervated left gland
      increased significantly (P less than 0.01, n = 7) to an extent slightly lower
      than that observed in right innervated gland. In the third group, intravenous
      injections of dimethylphenylpiperazinium (5 and 15 micrograms/kg) resulted in a
      dose-dependent increase (P less than 0.05, n = 7) in catecholamine output from
      both right innervated and left denervated gland. The results indicate that the
      present procedure of acute surgical adrenal denervation can eliminate the
      centrally mediated adrenal response, whereas the medullary secretory response to
      blood-borne substances remains intact. This model may be a useful tool for
      studying neuronal and humoral medullary secretory functions in vivo under various
      experimentally induced stress conditions.

PMID- 1996720
TI  - Neuropeptide Y suppresses sympathetic activity to interscapular brown adipose
      tissue in rats.
AB  - To investigate the effects of neuropeptide Y (NPY) on sympathetic nerve activity
      to interscapular brown adipose tissue (IBAT), we injected NPY into the third
      cerebroventricle (icv), medial preoptic area (MPOA), anterior hypothalamic area
      (AHA), paraventricular hypothalamic nucleus (PVN), ventromedial hypothalamic
      nucleus (VMN), and lateral hypothalamic area (LHA) of anesthetized rats.
      Multiunit discharges from sympathetic nerves to IBAT were recorded
      electrophysiologically. The icv injection of NPY suppressed sympathetic nerve
      activity in a dose-dependent manner, followed by a gradual recovery. The
      microinjection of NPY (25 pmol) unilaterally into the PVN also significantly
      suppressed the sympathetic nerve activity to IBAT. In contrast, microinjection of
      NPY into the MPOA significantly increased the sympathetic nerve activity. The
      injection of saline into either the PVN or MPOA had no significant effect on
      sympathetic nerve activity. The microinjection of NPY (25 pmol) into the AHA,
      VMN, or LHA did not change sympathetic nerve activity to IBAT. We conclude that
      central administration of NPY affects the sympathetic nerve activity to IBAT and
      that the suppressive effect of NPY, which may act in part through the PVN, is
      dominant to the stimulatory effect. The result is consistent with the hypothesis
      that NPY is a neurochemical modulator of the sympathetic nervous system which
      controls energy expenditure in IBAT.

PMID- 1996721
TI  - Coronary vasoconstriction during stimulation in hypothalamic defense region.
AB  - Previous studies have identified a site in lateral hypothalamus (LH) in which
      electrical stimulation elicits coronary vasoconstriction. We injected the
      retrogradely transported tracer Fast Blue to determine which brain regions
      project to LH. Projections to or through LH were found from the paraventricular
      nucleus (PVN) of the hypothalamus, bed nucleus of the stria terminalis (BNST),
      and dorsal raphe nucleus (DRN). In chloralose-anesthetized cats, electrical
      stimulation in DRN and BNST failed to increase coronary vascular resistance
      (CVR). However, stimulation lateral to PVN in the anterior hypothalamic area
      (AHA), a region not labeled by the tracer, caused a transient decrease in
      coronary blood flow similar to that elicited from LH. The increase in CVR was
      accompanied by hemodynamic changes that are characteristic of the defense
      reaction including a cholinergically mediated decrease in hindquarter vascular
      resistance. This response is likely due to activation of fibers of passage and
      not cell bodies, since cell bodies in the region were not retrogradely labeled
      and coronary vasoconstriction was not seen following microinjection of several
      excitatory amino acids into AHA. These data suggest that coronary
      vasoconstriction may be a component of the defense reaction elicited by
      electrical activation of AHA.

PMID- 1996722
TI  - Cardiac mechanical restitution in active and hibernating Richardson's ground
      squirrel.
AB  - The cardiac mechanical restitution was compared in papillary muscles between the
      active and the hibernating Richardson's ground squirrels at 0.1, 2.8, and 5 mM
      external Ca2+ concentration [( Ca2+]o). The amplitude of the restitution was
      significantly higher in hibernating animals between 37 and 7 degrees C at all
      [Ca2+]o. The first postrest contraction (F1) was highest at 20 degrees C and
      lower at 37 and 7 degrees C in both groups. The pause duration for maximum F1 was
      30 s in active but 10 s in hibernating animals at 37 degrees C and increased to
      100 s in both groups at 7 degrees C. The postrest potentiation was eliminated by
      10(-6) M ryanodine at 20 degrees C in both groups, and this inhibitory effect was
      more pronounced in the hibernating group. Together, our results suggest that the
      activator Ca2+ for excitation-contraction coupling is mainly derived from the
      sarcoplasmic reticulum (SR) pool in both active and hibernating ground squirrel,
      and the dependence on SR Ca2+ release via ryanodine-sensitive Ca2+ channels is
      more marked in the hibernating state. Furthermore, there is no significant
      difference in sensitivity of the cardiac mechanical restitution to [Ca2+]o
      between the active and the hibernating condition.

PMID- 1996723
TI  - Vascular tone influences arterial pressure lability after sinoaortic
      deafferentation.
AB  - Sinoaortic deafferentation (SAD) results in increased variability of arterial
      pressure. The purpose of this study was to investigate the contribution of
      nonneurogenic, peripheral vasomotor mechanisms to this arterial pressure
      lability. In rats with SAD, ganglionic blockade combined with either captopril or
      a V1-vasopressin receptor antagonist reduced the high lability. Under these
      conditions, continuous infusions of phenylephrine and the endogenous
      vasoconstrictors angiotensin II, epinephrine, and vasopressin increased lability,
      suggesting that the level of vascular tone is important for maintaining lability.
      Hemodynamic changes in individual vascular beds did not correlate with pressure
      lability; however, the sum of the changes in resistance, an estimate of changes
      in total peripheral resistance, was significantly correlated. These results
      suggest that 1) direct actions of endogenous vasoconstrictors can induce marked
      variations of arterial pressure, presumably by sustaining a high background of
      vascular tone, and 2) variations in resistance of individual vascular beds do not
      account for the lability of arterial pressure evoked by infusion of
      vasoconstrictors. We conclude that vascular tone of neural and/or humoral origin
      is critical for the generation of fluctuations in arterial pressure associated
      with deafferentation of baroreceptors.

PMID- 1996724
TI  - Altered sympathetic control of nutrient mobilization during physical exercise
      after lesions in the VMH.
AB  - To study the impact of obesity on sympathetic nervous regulation of nutrient
      mobilization, obese rats and lean controls were subjected to physical exercise.
      Male Wistar rats, rendered obese by bilateral electrolytic lesions of the
      ventromedial hypothalamus (VMH) were subjected to 15 min swimming. Permanent
      cardiac catheters allowed frequent blood sampling. At rest, glucose, free fatty
      acids (FFA), and insulin concentrations were elevated in the obese animals,
      whereas catecholamine levels were similar in both groups. During exercise,
      glucose concentrations reached higher values in the lesioned rats, whereas these
      animals did not display the normal FFA increment. Plasma insulin concentrations
      were suppressed in both groups, and the rate of suppression was very similar when
      expressed as percentage change from resting levels. There was no difference in
      plasma epinephrine responses during swimming, but the increase in norepinephrine
      was diminished in the obese animals. The results suggest that obesity after VMH
      lesion leads to reduced stimulation of lipolysis by norepinephrine and a
      predominant mobilization of glucose during exercise, both favoring glucose
      utilization and the accumulation of fat.

PMID- 1996725
TI  - Organum cavum pre-lamina terminalis, an undescribed brain organ in rats:
      morphology and physiology.
AB  - Morphological as well as physiological findings reported here point to the
      existence of a previously undescribed brain organ we refer to as the organum
      cavum pre-lamina terminalis (OCPLT). The organ is a hollow, sagittal, forebrain
      structure consisting of a vertical interhemispheric horn that overlies the
      anterior aspect of the lamina terminalis and a horizontal horn that lies in the
      septum below the corpus callosum. This horizontal horn was previously referred to
      as the cavum septi pellucidi, a vestigial anatomic curiosity. The narrow cavities
      of the horizontal and vertical horns join under the genu of the corpus callosum
      and communicate freely. The two horns do not communicate with the cerebral
      ventricular system or the subarachnoid spaces. Microinjections of greater than or
      equal to 0.2 ng angiotensin II into all regions of the cavity resulted in
      significant drinking, whereas injections into areas surrounding the cavities were
      ineffective. These data show that the organ is a discrete brain entity and
      displays high sensitivity to angiotensin II. These findings suggest that the
      OCPLT is another brain organ with significant effects on fluid and electrolyte
      homeostasis and perhaps other brain functions.

PMID- 1996726
TI  - Salt appetite in rat pups: ontogeny of angiotensin II-aldosterone synergy.
AB  - Preweanling rats were tested to determine whether angiotensin II (ANG II) and
      aldosterone (Aldo) act synergistically to enhance salt appetite at 12 and 17
      days. Twelve-day-old pups received one of four hormone treatments in four doses:
      1) ANG II only [1, 2, 10, or 100 ng pulse intracerebroventricular (icv)], 2) Aldo
      only (1, 2, 10, or 40 micrograms/day sc), 3) Aldo + ANG II (four individual doses
      combined), or 4) vehicle. Seventeen-day-old rats received the same treatments in
      two doses (2 or 100 ng ANG II; 2 or 40 micrograms Aldo). Pups were presatiated
      with milk through anterior oral catheters and then given either 4% NaCl or water
      for 30 min. Intake was assessed by body weight change. At both ages, ANG II
      enhanced salt (and water) intake, and Aldo enhanced salt (but not water) intake.
      Minimum effective doses were comparable to those reported for adults. ANG II-Aldo
      synergy was absent at 12 days and present at 17 days, when salt intake was 590%
      greater than the summed intakes evoked by ANG II and Aldo alone. The neural
      mechanisms for ANG II-Aldo synergy thus mature later than those mediating the
      hormone's individual actions in arousing salt appetite.

PMID- 1996727
TI  - Axial diffusion and Michaelis-Menten kinetics in oxygen delivery in rat
      peripheral nerve.
AB  - Our simulation of the release, diffusion, and consumption of oxygen in the
      capillaries and surrounding tissue of peripheral nerve now includes axial
      diffusion in blood and in surrounding tissue, in addition to bulk flow of blood
      and radial diffusion of oxygen out of the capillary. Our simulation assumes that
      the oxygen consumption of nerve tissue obeys Michaelis-Menten kinetics rather
      than zero-order kinetics as had been assumed in the Krogh model. We can calculate
      the oxygen tension at all points in the capillary and surrounding tissue as a
      function of distance from the center of the nearest capillary and distance along
      the capillary from the arterial to the venous end. Using average measured values
      for microcirculatory parameters in rat nerve, we calculated a distribution of
      oxygen tension values that agrees with experimentally measured distributions. The
      effects of axial diffusion and of Michaelis-Menten kinetics on the oxygen
      distributions were noticeable under normal conditions, but these effects were
      much more important in situations in which oxygen delivery was adversely
      affected.

PMID- 1996728
TI  - Perimyositis with perineuritis and myofiber type grouping in the eosinophilia
      myalgia syndrome associated with tryptophan ingestion.
AB  - Skeletal muscle biopsies from five patients with severe myalgias, peripheral
      eosinophilia, and a recent history of L-tryptophan ingestion were analyzed.
      Perimysial inflammation, predominantly mononuclear with variable numbers of
      eosinophils was seen (in five of five patients), which was perineurial (in three
      of five) and perivascular (in five of five) in location. Grouping of the myofiber
      types was identified by enzyme histochemistry in two of four patients; fresh
      muscle for histochemical studies was unavailable from one patient. An occasional
      degenerating myofiber was seen in only one patient, who was still ingesting L
      tryptophan at the time of biopsy. No vasculitis was seen. The focus of muscle
      injury in this syndrome appeared to be the perimysium and, in particular, the
      perineurial and perivascular connective tissue.

PMID- 1996729
TI  - Mucinous adenofibromas of the ovary. A report of 10 cases.
AB  - Mucinous epithelium is the most uncommon type identified in ovarian
      adenofibromas. Because of the rarity of mucinous adenofibromas and the presence
      of cytologic atypia in some, these neoplasms may be mistaken for low-grade
      metastatic adenocarcinoma. The clinicopathologic features of 10 mucinous
      adenofibromas are reviewed. They occurred in women 24 to 76 (mean, 51) years of
      age, were unilateral, and ranged in diameter from 1 to 25 cm. Seven tumors were
      classified as benign, containing glands lined by a single layer of mucin
      containing columnar cells. Three tumors that contained crowded glands lined by
      mucin-containing cells with mild to moderate nuclear atypia, nuclear
      stratification of up to three cells in thickness, and focal tufting were
      classified as benign with epithelial atypia. Most women had a hysterectomy and
      bilateral salpingo-oophorectomy. Follow-up information was available on six
      women, who were alive and well from 6 to 126 (mean 41) months after diagnosis.
      The identification of mucinous glands in typical fibromatous stroma should allow
      the distinction of these benign neoplasms from metastatic carcinomas.

PMID- 1996730
TI  - Pancreas transplant pathology. A morphologic, immunohistochemical, and electron
      microscopic comparison of allogeneic grafts with rejection, syngeneic grafts, and
      chronic pancreatitis.
AB  - In an effort to establish diagnostic criteria for rejection and recurrent disease
      in transplanted pancreas, a comparative study was performed based on clinical
      diagnosis. Clinical rejection was diagnosed in patients who had decreased urinary
      amylase or increased blood glucose; they were treated for rejection and improved.
      A clinical diagnosis of recurrent diabetes was made in syngeneic transplant
      recipients with islet dysfunction. In addition, two control groups were used-
      nontransplant, nondiabetic pancreatitis patients and pretransplant normal
      biopsies from patients in the study. Morphologically, tissues were assessed for
      acinar inflammation, ductal changes, islet and nerve inflammation, and vascular
      changes. Immunohistochemical staining for insulin and glucagon was also performed
      to quantitate differences between the groups. Vascular changes (endothelialitis,
      vasculitis, obliterative endarteritis) were specific for rejection. Also,
      rejection was characterized by a lymphocytic or mixed infiltrate that involved
      the ducts. Recurrent diabetes was characterized by selective loss of beta cells
      with isletitis. Leukocyte common antigen and UCHL1 staining was helpful in
      identifying islet inflammation. An insulin/glucagon ratio of less than 1.0
      appears to be specific for recurrent disease and in the absence of isletitis is a
      reasonable method for detecting recurrent disease at an early stage.

PMID- 1996731
TI  - Nasal lymphoma. A clinicopathologic study with immunophenotypic and genotypic
      analysis.
AB  - We studied 13 cases of malignant lymphoma involving the nasal cavity, in six men
      and seven women, from 27 to 92 years of age (mean, 56 years; median, 55 years).
      All lymphomas had a diffuse pattern, with 10 of large-cell type (six
      immunoblastic polymorphous, one immunoblastic, three large cleaved cell), one of
      mixed small- and large-cell type and one of small cleaved-cell type. One case
      could not be subclassified. Angioinvasion and prominent necrosis were seen in 10
      cases. Pseudoepitheliomatous hyperplasia of the overlying epithelium was present
      in five cases. Immunohistochemical studies on frozen or paraffin sections in nine
      cases revealed that the atypical cells were T cells in four cases (CD8+ in two
      cases) and B cells with monotypic immunoglobulin in two cases. In three cases,
      the findings were suggestive but not diagnostic of T lineage. Genotypic analysis
      in one of two cases of T-cell lymphoma revealed clonal rearrangement of the genes
      for beta and gamma chains of the T-cell receptor. Patients were treated initially
      with local radiation therapy (10 cases) or with radiation and chemotherapy (three
      cases). Eight patients (62%) had no relapse and were free of disease between 9
      months and 23 years (mean, 6 years 5 months; median 2 years 1 month) after
      diagnosis. Five patients developed recurrent disease, three of whom were
      successfully salvaged. One patient was alive with tumor at the time of last
      follow-up and one died with tumor. Among cases of malignant lymphoma presenting
      with involvement of the nasal cavity, we find a high proportion of angioinvasive,
      diffuse large-cell lymphomas, with a predominance of T-cell type, and a
      relatively good prognosis when treated with radiation therapy.

PMID- 1996732
TI  - The normal esophagus.
AB  - The diagnosis of diseases affecting the esophagus frequently depends on a
      knowledge of the normal anatomy and histology of the esophagus. This paper
      describes and relates normal esophageal gross and histological features to
      pathological conditions affecting the esophagus. Special attention is given to
      the problems of diagnosis encountered when confronted with mucosal biopsy
      specimens from the gastroesophageal junction.

PMID- 1996733
TI  - Hosts on which nymphal Ixodes ricinus most abundantly feed.
AB  - To identify hosts that may serve as European reservoirs for the agent of Lyme
      disease, Borrelia burgdorferi, we determined whether nymphal Ixodes ricinus feed
      mainly on particular mice (Apodemus flavicollis or A. agrarius), voles
      (Clethrionomys glareolus) or on sand lizards (Lacerta agilis) and whether the
      abundance of these hosts corresponds to the seasonal activity of the subadult
      stages of the vector tick. In all sites, the mice appeared most heavily infested
      by larvae; at least seven parasitized each mouse, about three per vole and four
      per lizard. Many fewer nymphal I. ricinus parasitized A. flavicollis and C.
      glareolus than did larvae. Although more than 30 times as many larval than
      nymphal ticks parasitized the two most abundant hosts (C. glareolus and A.
      flavicollis), about 15 times as many fed on A. agrarius and twice as many on
      lizards. Nymphal and larval ticks fed on rodents at about the same time. Lizards
      were most abundantly parasitized by nymphs somewhat earlier than by larvae. Early
      in the season of transmission of Lyme disease, virtually all A. agrarius as well
      as lizards were potentially exposed to spirochetes borne by nymphal I. ricinus.
      We concluded that larval and nymphal I. ricinus differentially parasitize
      different hosts. Because so many of these nymphs feed on them, A. agrarius may
      more effectively serve as reservoirs for the agent of Lyme disease than do other
      putative reservoir hosts. The presence of lizards may inhibit transmission.

PMID- 1996734
TI  - Detection of Plasmodium falciparum infection with the fluorescent dye,
      benzothiocarboxypurine.
AB  - The fluorescent dye benzothiocarboxypurine (BCP) intensely stains nucleic acids.
      The dye does not penetrate viable white blood cells but does stain these cells
      following fixation. It has also been found that the dye stains the nucleic acid
      of viable Plasmodium falciparum. We have subsequently evaluated the staining of
      P. falciparum by benzothiocarboxypurine within red blood cells and have found
      that the red blood cell membrane is freely permeable to this dye and consequently
      P. falciparum is stained within the red blood cell. This finding prompted an in
      depth analysis of the dye in the laboratory and in a field study as an
      alternative to Giemsa-stained blood smears and as a means of enhancing the
      microscopic diagnosis of malarial infection. In a field study the BCP dye allowed
      detection of malaria in fresh blood at a level equivalent to the Giemsa method
      (parasitemia ranged from 0.01% to 30%). The BCP staining procedure could also be
      used with fixed specimens although the differential staining characteristics were
      lost following specimen preparation. Of 111 blinded samples obtained in the field
      22 were negative by Giemsa-stained thin smear, 16 were negative on thick smear
      and the same 16 were negative by BCP analysis. We have found that the BCP dye
      offers many advantages compared with the microscopic diagnosis of P. falciparum
      infection with standard Giemsa stains. These advantages are especially evident in
      conditions of low parasitemia, in the speed of staining and evaluation, and the
      relatively low level of training required to provide consistent results.

PMID- 1996735
TI  - Acridine orange fluorescent microscopy and the detection of malaria in
      populations with low-density parasitemia.
AB  - Detection of low-density malaria parasites with Giemsa-stained thick smears (G
      TS) requires time and experience and becomes impractical with high sample loads.
      Acridine orange fluorescent microscopy (AO/FM) of capillary centrifuged blood may
      offer an alternative technique. We compared AO/FM readings with G-TS in 290
      specimens from asymptomatic people in Thai villages endemic for malaria. AO/FM
      specimens were prepared in modified capillary tubes coated with acridine orange
      (Quantitative Buffy Coat or "QBC tubes") and examined under a fluorescent
      microscope. Twenty-three (85.2%) of the 27 specimens found positive by G-TS had
      under 100 parasites/microliters blood (less than 35 parasites/200 microscopic
      fields). The overall AO/FM sensitivity was 78.9% [range: 66.7% (10/15)-86.7%
      (13/15)]. For Plasmodium falciparum, regardless of stages, the sensitivities
      varied from 66.7% (8/12) to 91.7% (11/12). AO/FM performed better for P.
      falciparum than for Plasmodium vivax and for asexual than for sexual stages of
      the parasite. However, the species- and stage-specific results must be
      interpreted with caution because of the small sample sizes and very low parasite
      densities involved. The test specificity was 96.6% [range: 95.6% (263/275)-97.1%
      (263/271)]. These levels of accuracy plus the known advantages of AO/FM suggest
      that the test, supplemented with G-TS to improve species and stage
      differentiation, is also useful for screening low-density parasitemias.

PMID- 1996736
TI  - Characteristics of natural antibody responses to the circumsporozoite protein of
      Plasmodium vivax.
AB  - The antibody response to the prototype circumsporozoite (CS) protein of
      Plasmodium vivax (CSPV) was studied in Thai soldiers experiencing occupational
      malaria. Seventy-four (65%) of 114 men followed during assignment to a malaria
      transmission area developed blood-stage infection with P. vivax. IgG antibodies
      against the central repeat region of the CSPV protein were quantitated by ELISA
      using the recombinant protein, NS181V20, as the capture antigen. One quarter of
      the subjects had detectable anti-CSPV antibodies at the beginning of the study.
      CSPV antibody seroconversion was documented in 16 of 26 subjects assessed during
      their first observed episodes of vivax malaria. This antibody response was of
      moderate magnitude, fell off after the first week post-diagnosis and appeared, at
      the low levels observed, to be unassociated with protection. Continued assessment
      of anti-CSPV antibody after subjects left the transmission area found no increase
      associated with release of P. vivax. These findings indicate that CS antibody
      responses to P. vivax during occupational malaria share many characteristics with
      responses to P. falciparum.

PMID- 1996737
TI  - Plasmodium vivax sporozoite antibodies in individuals exposed during a single
      malaria outbreak in a non-endemic area.
AB  - We studied seroreactivity against Plasmodium vivax antigens in 62 individuals
      living in a small community near Mantena, Minas Gerais, Brazil, an area outside
      the endemic malaria zone Brazil. Eight months earlier, there had been
      transmission of P. vivax for a period of 50 days, which was then totally
      controlled by chemotherapy and insecticides. An anti-sporozoite response,
      measured by ELISA using a recombinant protein expressed in yeast, was detected in
      45% (14 of 31) of individuals eight months after infection and persisted for 20
      months in 12%. Eighteen individuals were treated prophylactically for malaria
      because they lived in houses in which an overt infection had occurred. Seven of
      these individuals were ELISA positive; of these, 5 had antibodies against the
      blood stage parasites. Among 13 other individuals in the endemic area who did not
      have positive smears, had not been ill, and had not received prophylaxis, five
      were anti-circumsporozoite positive up to a 40-fold serum dilution. They did not
      develop asexual blood stage antibodies and remained parasite-free for the
      following 20 months.

PMID- 1996738
TI  - Comparison of high dose ivermectin and diethylcarbamazine for activity against
      bancroftian filariasis in Haiti.
AB  - This three-phase study was designed to compare high dose ivermectin with a
      standard diethylcarbamazine (DEC) regimen for patient tolerability, potential to
      kill adult filaria, and duration of microfilarial suppression in 30 Haitian
      subjects with Wuchereria bancrofti microfilaremia. All were first given a 1-mg
      oral dose of ivermectin (phase 1) to reduce microfilaria densities. Participants
      were randomized into three groups: Group 1 received DEC (6mg/kg per day for 12
      days), Group 2 received 200 mcg/kg of ivermectin, and Group 3 received 400 mcg/kg
      of ivermectin (200 mcg/kg per day for 2 days). All drug regimens were well
      tolerated with few adverse reactions. Most reactions occurred during phase I and
      consisted primarily of headache, fever, and myalgia. At the end of phase 1, 27 of
      30 (90%) patients were microfilaria negative. During phase 2, four of the six men
      receiving DEC developed scrotal reactions suggesting killing adult worms; no such
      reactions were noted in 10 men receiving ivermectin (p less than 0.05). At one
      year follow up (phase 3), all treatment groups had less than 10% return to
      pretreatment microfilaria levels. The mean percent of baseline microfilaria
      counts were for Group 1, 0.9% (range 0-5%); Group 2, 8.2% (range 0-31%); and
      Group 3, 3.8% (range 0-25%). Seven individuals in Group 1 were microfilaria
      negative, while only one and three individuals were microfilaria-negative in
      Groups 2 and 3, respectively. These results suggest that DEC causes more damage
      to the adult worms and greater reduction in microfilaria densities than
      ivermectin, but that high doses of ivermectin may suppress microfilaremia in
      lymphatic filariasis for periods much longer than previously reported.

PMID- 1996739
TI  - Immunization of owl monkeys with the ring-infected erythrocyte surface antigen of
      Plasmodium falciparum.
AB  - Aotus nancymai were immunized with the 4-mer, 8-mer, and 11-mer repeat peptides
      of the ring-infected erythrocyte surface antigen molecule of Plasmodium
      falciparum conjugated to diphtheria toxoid with muramyl dipeptide (MDP) as
      adjuvant. Immunization failed to induce protective immunity against the Uganda
      Palo Alto strain of P. falciparum as judged by maximum levels of parasitemia of
      immunized monkeys relative to those of controls. The fused polypeptide FPAg632,
      when combined with MDP, also failed to induce protective immunity. However, the
      maximum level of parasitemia and serologic response to the 11-mer peptide were
      inversely correlated. The safety of the use of MDP was evident.

PMID- 1996740
TI  - A spleen is not necessary to resolve infections with Plasmodium yoelii.
AB  - The role of the spleen in resistance to infections with nonlethal Plasmodium
      yoelii 17x is dependent upon the genotype of the host. Thus, DBA/2 (D2) mice
      infected with P. yoelii 17x were not adversely affected by removal of the spleen,
      while splenectomized C57BL/6 (B6) or Balb/c mice failed to resolve their
      infections and eventually died. The levels of parasitemia were lower in
      splenectomized mice compared to intact controls; however, splenectomized mice
      became as anemic as did spleen-intact controls. Splenectomy resulted in the
      appearance of large aggregates of mononuclear cells in the livers of infected
      mice and also altered the liver/body weight ratios. These results indicate that
      D2 mice have a spleen-independent mechanism of clearing parasites which is
      lacking in B6 and Balb/c mice.

PMID- 1996741
TI  - Intestinal cryptosporidiosis: pathophysiologic alterations and specific cellular
      and humoral immune responses in rnu/+ and rnu/rnu (athymic) rats.
AB  - In order to develop an experimental model of symptomatic cryptosporidiosis in an
      immunosuppressed mammal, we investigated the pathophysiology of infection with
      Cryptosporidium and the humoral and cellular host responses in rnu/rnu (athymic)
      rats and their heterozygous (rnu/+) littermates by challenging suckling rats with
      greater than or equal to 2.5 x 10(6) Cryptosporidium oocytes oro-gastrically.
      Normal and immunodeficient animals were followed for onset and duration of
      infection (fecal oocysts), physiologic consequences (diarrhea, impaired weight
      gain, brush-border enzyme activities), and immunologic response (both B- and T
      lymphocyte-mediated). Homozygosity for the rnu gene was associated with
      protracted cryptosporidial infections; shedding for up to 52 days occurred, and
      delay in weight gain was noted in rnu/rnu-infected compared with rnu/rnu
      uninfected rats (p less than 0.05). In contrast, cryptosporidial challenge of
      rnu/+ rats resulted in self-resolving infections, occasionally with transient
      diarrhea lasting four days or less occurring 10-15 days after oro-gastric
      challenge. The latter animals mounted a cell-mediated immune response to
      Cryptosporidium: three months after challenge, five of five rnu/+ rats
      demonstrated positive skin test responses to a subcutaneous 3.5 micrograms dose
      of cryptosporidial antigen. Further, sera from 6 rnu/+ rats taken two to three
      months after oro-gastric oocyst challenge exhibited specific anticryptosporidial
      immunoglobulin binding (A405 = 0.96), compared to that of seven uninfected rnu/+
      controls (A405 = 0.09, P less than 0.02). Macromolecules of 150, 105, and 88 kD
      in the Cryptosporidium antigen preparation were bound by serum immunoglobulin
      from previously infected, recovered rnu/+ rats. Two brush-border enzymes (lactase
      and alkaline phosphatase) were markedly reduced in the ileum 8-10 days after oro
      gastric challenge in rats with diarrhea and oocyst shedding. We find the rnu/rnu
      (athymic, nude) rat provides a useful model for study of prolonged
      cryptosporidial infection with impaired weight loss, brush-border enzyme
      alteration and intermittent diarrhea. These studies further suggest that a T
      lymphocyte population is involved in recovery from Cryptosporidium infection and
      that this recovery is associated with both cellular and humoral immune responses
      to specific cryptosporidial antigenic macromolecules. This model should open
      further avenues for the study of the pathogenesis and protective immunity in
      cryptosporidial infection.

PMID- 1996742
TI  - Isoenzyme profiles of four strains of Giardia lamblia and their infectivity to
      jirds.
AB  - The infectivity to jirds (Meriones unguiculatus) and the cyst excretion pattern
      of a recently isolated strain of Giardia lamblia from Egypt, Strain CDC:1088:1
      (EGY), were compared to those of three well-established strains. All five jirds
      inoculated orally with strain UNO:0487:1 (UNO) became infected and began
      excreting cysts 3-6 days post-infection (dpi); no cysts were detected between 8
      12 dpi after which time cysts were produced through day 19. Four of the five
      jirds infected with Strain ATCC:30957 (WB) and three of the five jirds infected
      with strain CDC:0284:1 (VA) excreted cysts from 6-20 dpi and 6-22 dpi,
      respectively. One of five jirds inoculated with EGY excreted cysts on 8 dpi only.
      At necropsy, trophozoites were recovered from only three UNO-infected jirds but
      from all WB- and VA-infected jirds that excreted cysts. The one jird which
      excreted cysts of EGY was negative at necropsy, but EGY trophozoites were found
      in one non-patient jird. Isoelectric focusing indicated that these four strains
      of G. lamblia represented three zymodemes. WB and VA were assigned to one
      zymodeme, EGY to a second, and UNO, which shared common bands with both other
      zymodemes, to the third. Although the similarities and differences in infectivity
      and cyst excretion patterns appear to coincide with the zymodemes to which the
      strains can be assigned, further study is needed to examine the parasitologic
      behavior of these strains in relation to isoenzyme patterns.

PMID- 1996743
TI  - The effect of chloroquine prophylaxis on yellow fever vaccine antibody response:
      comparison of plaque reduction neutralization test and enzyme-linked
      immunosorbent assay.
AB  - Weekly oral chloroquine prophylaxis for malaria has been associated with impaired
      antibody response to intradermal rabies vaccination. Experimental data indicate
      that chloroquine may inhibit yellow fever virus in vitro, yet there has been no
      clinical evidence to suggest that antibody response to yellow fever vaccine is
      impaired by concomitant oral administration of chloroquine. A prospective trial
      was undertaken to evaluate the antibody response to yellow fever 17D vaccine
      (Connaught Laboratories) of volunteers who were randomized to taking either
      chloroquine or no drug. Of fifty subjects, 28 were randomized to taking
      chloroquine, 22 were randomized to taking no drug. Yellow fever 17D vaccine was
      administered on day 0 and blood sampled on days 0, 14, 35 and 210. Chloroquine
      was administered weekly for four weeks. There was no significant difference in
      peak antibody titer by plaque reduction neutralization testing (PRNT) between the
      group that took chloroquine (mean log peak of reciprocal titer 1.43 +/- SD 0.60)
      with vaccine subcutaneously compared to vaccine-only group (mean log peak of
      reciprocal titer = 1.21 +/- 0.55). All fifty subjects seroconverted to yellow
      fever vaccine by day 210. ELISA testing was also performed on all subjects. The
      two tests showed good correlation (Spearman r = 0.675), although ELISA readings
      were positive by day 14 in significantly more subjects (p = .01). We conclude
      that routine anti-malarial doses of chloroquine do not affect antibody response
      to yellow fever 17D vaccine. ELISA testing, a less complex and less time
      consuming test, correlates well with PRNT and is proposed for additional trials
      to measure yellow fever 17D vaccine response in flavivirus non-immune subjects.

PMID- 1996744
TI  - Venomous snakebite in eastern Ecuador.
AB  - Treatment outcome of 294 hospitalized victims of snakebite injuries in Eastern
      Ecuador are reported, documenting high rates of morbidity and mortality. One or
      more major complications occurred in 25% of patients. Complications included
      blood loss severe enough to require transfusion (29 patients), abscess (26
      patients), intracranial hemorrhage (15 patients) and major tissue loss (10
      patients). Sixteen patients died, yielding a mortality rate of 5.4%. Death
      resulted from intracranial hemorrhage in 12 patients and from sequelae of
      hypovolemic shock in 4 patients.

PMID- 1996745
TI  - Influence of temperature of bupivacaine on spread of spinal analgesia.
AB  - A prospective, randomised study was performed to investigate the influence of
      temperature on sensory blockade in spinal anaesthesia. Three ml of plain
      bupivacaine 0.5% were injected intrathecally at either 4 degrees C, room
      temperature, or 37 degrees C. There were 10 patients in each group, who were kept
      sitting for 2 minutes after injection. The maximum level of sensory blockade was
      significantly higher (p less than 0.01) in the group who received the solution
      adjusted to 37 degrees C, and variability of level was smaller (p less than
      0.05). Time to two-segment regression was shorter in the 37 degrees C group than
      in the 4 degrees C group (p less than 0.05). Hypotension required administration
      of ephedrine more often in the 37 degrees C group (p less than 0.05). It is
      concluded that the use of plain bupivacaine 0.5% adjusted to 37 degrees C results
      in a higher and more predictable sensory blockade.

PMID- 1996746
TI  - Propofol for induction and maintenance of anaesthesia at caesarean section. A
      comparison with thiopentone/enflurane.
AB  - A propofol infusion regimen and a standard general anaesthetic were compared in
      40 Chinese women undergoing elective Caesarean section. Twenty patients received
      propofol 2 mg/kg for induction of anaesthesia followed by propofol 6 mg/kg/hour,
      while 20 patients received thiopentone 4 mg/kg with enflurane 1% for maintenance
      of anaesthesia. All patients were given atracurium and their lungs ventilated
      with nitrous oxide 50% in oxygen until delivery of the neonate. The hypertensive
      response after intubation was of shorter duration in the propofol group compared
      with the thiopentone group. Induction to delivery times ranged from 5 to 14
      minutes and neonates from both groups had similar and satisfactory Apgar scores.
      Neurologic and Adaptive Capacity Scores and umbilical cord blood gas analysis.
      However, a prolonged propofol infusion time before delivery may cause lower
      Neurologic and Adaptive Capacity Scores. There were no differences in maternal
      recovery times or psychomotor performance.

PMID- 1996747
TI  - Ketamine as analgesic for total intravenous anaesthesia with propofol.
AB  - A prospective study of 18 patients who underwent noncardiac surgery was performed
      to study the use of ketamine as an analgesic during total intravenous anaesthesia
      with propofol. A comparison was made with the combination propofol/fentanyl. The
      propofol/ketamine combination resulted in haemodynamically stable anaesthesia
      without the need for additional analgesics. Postoperative behaviour was normal in
      all patients and none of the patients reported dreaming during or after the
      operation. Propofol seems to be effective in eliminating side effects of a
      subanaesthetic dose of ketamine in humans. We recommend the propofol/ketamine
      combination for total intravenous anaesthesia for surgery when stable
      haemodynamics are required.

PMID- 1996748
TI  - Midazolam-induced benzodiazepine withdrawal syndrome.
AB  - A case history of a patient who developed severe anxiety and agitation on two
      occasions after discontinuation of a midazolam infusion is presented. The
      withdrawal symptoms interfered with effective mechanical ventilation and the
      patient required the reintroduction of a long-acting benzodiazepine to treat the
      withdrawal state and to facilitate weaning from mechanical ventilation.

PMID- 1996749
TI  - A comparison of the performance of 20 pulse oximeters under conditions of poor
      perfusion.
AB  - The performance of 20 pulse oximeters with finger probes was evaluated by
      comparison of their readings with directly measured arterial blood oxygen
      saturations. The samples were taken from patients who had undergone cardiac
      surgery under hypothermic cardiopulmonary bypass and had poor peripheral
      perfusion. The mean difference (bias, accuracy), standard deviation (precision)
      and drop-out rate for each pulse oximeter was determined. An overall ranking of
      performance of each pulse oximeter was calculated using five criteria (accuracy,
      precision, number of readings within 3% of standard, percentage of readings given
      within 3% of standard, expected overread limit in 95% of cases). Two pulse
      oximeters achieved a combination of accuracy and precision such that 95% of
      measurements would be expected to be within 4% of the co-oximeter value; these
      two also had the lowest drop-out rate.

PMID- 1996750
TI  - Response to suxamethonium in a myasthenic patient during remission.
AB  - A cumulative dose followed by an infusion was used to determine the dose response
      to suxamethonium in a patient with diagnosed myasthenia gravis who was in true
      remission (asymptomatic while receiving no therapy). The ED50 and ED90 values for
      suxamethonium were 0.08 mg/kg and 0.20 mg/kg, and an infusion rate of 3.2
      mg/kg/hour was required to maintain a 90-95% depression of the single twitch
      response as monitored by integrated electromyography. These values are within the
      range for normal patients, and we conclude that myasthenic patients during a true
      remission may not demonstrate resistance to suxamethonium.

PMID- 1996751
TI  - Emery-Dreifuss muscular dystrophy.
AB  - Emery-Dreifuss syndrome is a rare form of muscular dystrophy associated with
      cardiac complications that lead to sudden death. The disorder and its potential
      anaesthetic implications in the management of a patient who presented for
      orthopaedic surgery is described.

PMID- 1996752
TI  - Emergency adenotonsillectomy for acute postoperative upper airway obstruction.
AB  - Peri-operative acute upper airway obstruction may be life-threatening. A case is
      reported of a child with severe adenotonsillar hypertrophy who developed acute
      upper airway obstruction after a routine surgical procedure and required
      emergency adenotonsillectomy. The importance of pre-operative assessment is
      stressed.

PMID- 1996753
TI  - Non-drug related asystole associated with anaesthetic induction.
AB  - A patient is presented where routine venepuncture associated with anaesthetic
      induction resulted in bradycardia and asystole. The case highlights the need for
      special caution with, and ECG monitoring throughout induction for, patients with
      a history of syncope. It also demonstrates the need for caution when attributing
      cardiovascular events during induction to the effect of the induction agents
      used.

PMID- 1996754
TI  - Rupture of the oesophagus during cricoid pressure.
AB  - Rupture of the oesophagus occurred during the application of cricoid pressure at
      induction of anaesthesia when the patient vomited. The patient, who was bleeding
      from a gastric ulcer, was found to have a lower oesophageal tear which, although
      repaired at operation, resulted in a fatal mediastinitis.

PMID- 1996755
TI  - Accidental bronchial intubation with RAE tubes.
AB  - Performed tracheal tubes are used frequently in paediatric anaesthesia. A feature
      which contributes to their popularity is the belief that they can be positioned
      more reliably than conventional tracheal tubes because of their design. We
      studied a group of 40 patients in whom the incidence of bronchial intubation was
      20%. The tube was too long in 32% of patients, although the tube size was
      appropriate for the child's age in all patients. The consequences and outcome of
      this complication are discussed.

PMID- 1996756
TI  - A comparison of patient rewarming devices after cardiac surgery.
AB  - Three regimens for rewarming patients after cardiac surgery involving hypothermic
      cardiopulmonary bypass were studied in 30 patients. The control group (n = 10)
      received no active rewarming, the oesophageal group (n = 10) was warmed centrally
      using an oesophageal heat exchanger and the radiant group (n = 10) was warmed
      peripherally with an overhead radiant heater. There were no statistically
      significant differences between the groups apart from the higher mean skin
      temperatures in the peripheral group.

PMID- 1996757
TI  - Dr F.P. de Caux--the first user of curare for anesthesia in England.
AB  - Curare was used in the 19th century in England by a wide variety of scientists,
      physicians and veterinarians. Their experiments indicated many of the properties
      of the drug, but its clinical usage remained very limited and was reserved for
      cases of tetanus, hydrophobia and strychnine poisoning. Griffith and Johnson are
      usually credited with the introduction of curare into clinical anaesthesia in
      1942, but a Dr F.P. de Caux working at the North Middlesex Hospital, London, in
      1928 utilised curare in a series of seven patients. His work was not widely
      publicized and this contribution to anaesthetic history has been overlooked by
      subsequent authors.

PMID- 1996758
TI  - Minimum oxygen requirements during anaesthesia with the Triservice anaesthetic
      apparatus. A study of drawover anaesthesia in the young adult.
AB  - Thirty-six servicemen were anaesthetised using the Triservice anaesthetic
      apparatus. They were allocated randomly into one of two groups, to breathe
      spontaneously or to receive artificial ventilation, and into subgroups who were
      given air alone, or air supplemented with 1 or 4 litres/minute of oxygen. A
      further 12 subjects were studied subsequently using 0.5 litres/minute of added
      oxygen. Intra-operative blood gases were compared with those of awake
      premedicated controls. Artificial ventilation was associated with an unchanged
      arterial oxygen tension with air alone; in the other subgroups arterial oxygen
      tension was higher than with spontaneous respiration when related to inspired
      oxygen fraction (p less than 0.05). Air anaesthesia caused significant hypoxaemia
      with spontaneous ventilation (p less than 0.05), and 50% of the subjects required
      assisted ventilation. There was also a significant respiratory acidosis (p less
      than 0.05). Intermittent positive pressure ventilation is the method of choice
      for field anaesthesia when oxygen is unavailable. Spontaneous respiration must be
      supplemented with at least 0.5 litres minute of oxygen.

PMID- 1996759
TI  - The role of a critical care unit in an epidemic.
AB  - The role of a critical care unit in life-threatening situations is well
      established. The management of 52 children with acute gastroenteritis and 22
      children with acute paralytic poliomyelitis as part of recent epidemics is
      described. The solutions to the problems in the critical care management of these
      74 victims (out of a total of 6197 patients admitted during the epidemics) are
      discussed.

PMID- 1996760
TI  - Factors that influence the induction dose of propofol.
AB  - Factors that influence the induction of anaesthesia with propofol were
      investigated in a prospective study of 1000 patients. Pre-operative albumin and
      urea concentrations correlated with the minimum induction dose of propofol, but
      less strong correlations were found with haemoglobin, globulin and total protein
      concentrations. Age was an important influence on the induction dose of propofol
      (r = -0.34) which was also closely related to ASA grade. Induction of anaesthesia
      with propofol is dependent on a number of variables, and this study suggests that
      pre-operative albumin and urea concentrations are important.

PMID- 1996761
TI  - Awareness during caesarean section.
AB  - Between 1982 and 1989 over 3000 patients were questioned about recall and
      dreaming after general anaesthesia for Caesarean section. Some 28 (0.9%) patients
      were able to recall something of their operation and 189 (6.1%) reported dreams.
      There was uniform adherence to a rigid anaesthetic protocol up to and including
      1985, but a much publicized incident reported from the courtroom stimulated a
      relaxation of this regimen. Consequently the incidence of awareness decreased
      from 1.3% to 0.4%, and the incidence of dreaming was also reduced. Recollections
      of surgery were confined to manipulations, noises and voices. None of our
      patients complained of pain at the time of interview, although one since has. The
      inadequacies of the initial protocol and an approach to informed consent are
      discussed.

PMID- 1996762
TI  - Coagulation screening before epidural analgesia in pre-eclampsia.
AB  - A questionnaire survey of current practice at a small cross-section of obstetric
      units, covering 22% of all United Kingdom deliveries, revealed a marked lack of
      standard practice regarding requests for coagulation screens on pre-eclamptic
      patients who require epidural procedures. A retrospective audit was therefore
      carried out on 434 coagulation screens requested for pre-eclamptic patients in
      whom epidural analgesia might have been considered. Borderline abnormalities of
      coagulation were found in only 10 patients (2%). Platelet counts of less than 150
      x 10(9)/litre were present in 28% of cases. 'Significant' thrombocytopenia (less
      than 100 x 10(9)/litre) and all coagulation abnormalities were only encountered
      in severe pre-eclampsia (diastolic blood pressure of greater than 110 mmHg and
      proteinuria of + + or greater). Furthermore, coagulation abnormality was always
      associated with a reduced platelet count (mean, 97 x 10(9)/litre). This study
      would therefore support anaesthetic practice which restricted any requests for
      coagulation testing to severe pre-eclamptic patients only. For these patients
      first line testing could be limited to a platelet count.

PMID- 1996763
TI  - Modification of pain on injection of propofol--a comparison between lignocaine
      and procaine.
AB  - Pain on injection of propofol was assessed in a controlled, randomised study of
      273 patients. They received either lignocaine 10 mg, procaine 10 mg or isotonic
      saline 0.5 ml, 15 seconds before the injection of propofol into a vein on the
      back of the hand. The incidence of pain on injection in the control group (51%)
      was comparable with other studies. Lignocaine and procaine both significantly
      reduced the pain (35% and 34% respectively, p less than 0.05) but there was no
      statistical difference between these two groups.

PMID- 1996764
TI  - Supplementary oxygen and the laryngeal mask airway.

PMID- 1996765
TI  - Laryngeal mask airway and laryngeal spasm.

PMID- 1996766
TI  - Successful difficult intubation.

PMID- 1996767
TI  - A problem with thiopentone solution.

PMID- 1996768
TI  - Epidural catheterisation.

PMID- 1996769
TI  - Subcutaneous morphine.

PMID- 1996770
TI  - The pump that gave too much: accidental overinfusion of prostacyclin.

PMID- 1996771
TI  - Accidental intra-arterial injection of tubocurarine.

PMID- 1996772
TI  - Hazards from homely anaesthetic rooms.

PMID- 1996773
TI  - Persistent erection and general anaesthesia.

PMID- 1996774
TI  - Inducible perivascular cells contribute to the neochondrogenesis in grafted
      perichondrium.
AB  - Autogeneic perichondrium was implanted above the cremaster muscle of the rat, and
      the new formation of two types of cartilage (types I and and II) was confirmed.
      Also, granulation tissue was observed before the type II cartilage formation.
      Under these conditions, the contribution to the neocartilage of graft bed derived
      cells, mainly of the venule pericytes, was studied. To follow the pericyte
      lineage, we used a marker--Monastral Blue B--the administration of which was
      based on the principle of vascular labeling. While the perichondrium was kept
      free, before its implantation, the preformed (preexisting) venules in the
      cremaster muscle were exclusively labeled with Monastral Blue B, which was
      incorporated into the cytoplasm of pericytes and endothelial cells. After
      perichondrium implantation, the following sequence in tracer distribution was
      demonstrated. During the earlier stages, labeling was restricted to the pericytes
      and endothelial cells of venules in the graft bed. Later the tracer was observed
      in some endothelial cells and pericytes of the growing vessels and in fibroblast
      like cells of the granulation tissue. Finally, some type II neochondrocytes
      appeared labeled. Tracer was not found in type I neochondrocytes. The presence of
      label in type II neochondrocytes demonstrates that they arise from progenitor
      cells present in the graft bed, principally from small venule pericytes.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1996775
TI  - Sympathetic innervation of the hindlimb arterial system in the giraffe (Giraffa
      camelopardalis).
AB  - We report the distribution of sympathetic nerves in the hindlimb arterial system
      of the giraffe based on the histochemical demonstration of monoamines by the
      sucrose-potassium phosphate-glyoxylic acid method. It is noted that the hindlimb
      arterial system shows regional variations in its sympathetic innervation with
      regard to the density and the penetration of the nerves into the tunica media not
      hitherto described. The femoral and popliteal arteries showed a paucity of
      sympathetic innervation. Distally the dorsal pedal and great metatarsal arteries
      showed sparse sympathetic innervation characterized by a tendency toward
      exclusion of the nerves toward the outer layers of the tunica media. In contrast,
      the anterior (cranial) tibial artery in the leg revealed a relatively rich
      pattern of sympathetic innervation and a greater penetration of the nerves into
      the tunica media. The latter part of the arterial system showed a marked
      thickening of the tunica media and luminal narrowing, thus suggesting a
      "sphincteric" function. It is conceivable that this sphincter subserves a dual
      function, namely, to modulate blood flow to the distal parts of the limbs, and
      secondly to channel blood to the thigh and crural musculature. Pertinent to this
      is the fact that the presumptive sphincter occurs immediately after the crural
      muscular branches are given off.

PMID- 1996776
TI  - Ectopic colonization of primordial germ cells in the chick embryo lacking the
      gonads.
AB  - Chick primordial germ cells (PGCs) first appear in the extraembryonic region in
      the early embryo, then temporarily circulate via the blood vascular system and
      finally migrate into the gonadal anlagen. In the present study, we examined the
      trend of ectopic distribution of PGCs in the chick embryo when its future gonadal
      region had been removed at an early stage. Embryos at stage 10, from which the
      caudal third region was excised, were incubated until they reached stages 14 to
      20. In embryos at stage 14, about 80% of the total PGCs were found in the
      capillaries of the yolk sac, whereas others were observed in the head, mainly in
      the mesenchyme and small vessels close to the neural tube. From stage 18 onward,
      many PGCs accumulated in the embryo proper; about 90% of them colonized in the
      head region around the neural tube. These ectopic PGCs in the head were found in
      the capillaries, sometimes as thrombi or emerging from them into the adjacent
      mesenchyme. These results show that, when the chick embryo lacked gonads, the
      PGCs could be concentrated in the head region and migrated from the capillaries
      into the mesenchyme.

PMID- 1996777
TI  - Spatial disorder of collagens in the great vessels, associated with congenital
      heart defects.
AB  - Surgical ablation of the cardiac neural crest from the chicken embryo results in
      persistent truncus arteriosus (PTA) and a change in the elastic laminae of the
      great vessels, wherein elastin and the elastin microfibril show significant
      spatial disorder. The purpose of this study was to test the hypothesis that the
      interstitial collagens would also be disordered in the elastic laminae of chicken
      embryos with PTA. The birefringence characteristics of interstitial collagen were
      examined to evaluate spatial ordering. The results showed that collagen in the
      elastic laminae assumed an orderly configuration of well-defined fiber bundles in
      the great vessel walls of control embryos, whereas vessels from embryos with PTA
      lacked any distinct spatial order. Collagens type I and III were localized in the
      vessel walls. Type III collagen was the principal collagen of the elastic
      laminae, but was absent from the intima of all vessels. In the elastic laminae of
      vessels from control embryos, collagen type III showed well-defined fiber bundles
      whereas embryos with PTA had diffuse collagen type III in poorly defined laminae
      that were not separated by discrete layers of smooth muscle cells. Collagen type
      I was a minor component of the elastic laminae but formed robust pericellular
      fiber bundles throughout the media and intima. Collagen type I fibers appeared to
      be coarsened and less uniform in the vessels from embryos with PTA.

PMID- 1996778
TI  - A new technique for explantation and in vitro cultivation of chicken embryos.
AB  - A technique is described for explanting and cultivating chicken embryos in
      plastic drinking cups which have been modified with plastic wrap to reproduce the
      geometry and dimensions of the egg shell. Successful explantation rates of 97%
      are possible with a double-window technique, and survivability in cups exceeds
      that achievable in other in vitro systems (i.e., petri dishes). Long-term
      survival to the 21st day of incubation is seen routinely. This system with cups
      is less expensive than that with petri dishes, and simpler than that with plastic
      wrap/tripods. Thus, this new method of in vitro cultivation of chicken embryos
      improves upon explantation rate, survivability and system design, and has a wide
      range of applications in developmental biology, angiogenesis, cancer, and
      pharmacology research.

PMID- 1996779
TI  - Functional and structural changes of rat plantaris motoneurons following
      compensatory hypertrophy of the muscle.
AB  - The conduction velocity and histological structure of motoneurons innervating
      normal and hypertrophied rat plantaris muscles were investigated. Hypertrophy was
      produced by ablation of synergist muscles. Single motor units were obtained by
      ventral root dissection and conduction velocities measured. The structure of
      neurons was investigated following retrograde labeling with horseradish
      peroxidase. A combined silver, gold and cholinesterase staining method was
      developed to study the motor endplate. In addition, the peripheral nerve was
      fixed, embedded in Araldite, and sectioned for determination of axonal size and
      myelin thickness. Conduction velocity of motor axons decreased following
      hypertrophy of the skeletal muscle (control CV = 75.8 +/- 8.9 m s-1, n = 94,
      hypertrophy CV = 69.0 +/- 12.3 m s-1, n = 84). However, no alteration in the size
      of motor axons or myelin thickness could account for this alteration in
      conduction velocity. Mean motoneuronal soma size decreased following muscle
      hypertrophy (soma diameter: control 36.1 +/- 4.6 microns, n = 283, hypertrophy
      32.9 +/- 4.5 microns, n = 294). The complexity of the motor endplate increased
      following hypertrophy with an increased occurrence of nodal sprouts. In addition,
      the area of cholinesterase staining increased following hypertrophy (control
      588.1 +/- 297.2 microns 2, n = 269, hypertrophy 857.7 +/- 357.0 microns 2, n =
      269). This study found that both the morphological and physiological parameters
      of motoneurons innervating a hypertrophied muscle were shifted toward those of
      normal rat slow motor units.

PMID- 1996780
TI  - Transplantation of labeled fetal spinal cord fragments into juvenile myelin
      deficient rat spinal cord.
AB  - Minced and triturated fragments from the spinal cord of normal rat fetuses (15-18
      days gestation) labeled with the fluorescent dye fast blue (FB) were successfully
      transplanted into juvenile myelin-deficient rat spinal cord under direct
      observation. Clusters of myelinated fibers were found subsequently in the
      recipient spinal cord, and, by fluorescence microscopy, clusters of FB-labeled
      cells were found at corresponding sites. The results indicate that the surgical
      approach used is suitable for transplantation of tissue fragments into a defined
      region of juvenile rat spinal cord, that FB can be used to locate the
      transplanted cells subsequently, and that FB does not interfere with maturation
      of the donor glia or with myelin formation.

PMID- 1996781
TI  - The Golgi apparatus of rat pachytene spermatocytes during spermatogenesis.
AB  - A morphological and immunocytochemical study of the Golgi apparatus in pachytene
      spermatocytes was performed in an effort to correlate the structure and function
      of this organelle during meiotic prophase. In stages I-III of the cycle, the
      Golgi complex of pachytene spermatocytes is a flattened discoid, 0.5-1 microns in
      diameter, composed of vesicles interspersed with classically described Golgi
      cisternae. During subsequent maturation of pachytene spermatocytes (stages IV
      XIII), the size of the Golgi complex increases significantly, attaining a size of
      2-3 microns. However, unlike pachytene spermatocytes of stages I-III, the
      majority of the Golgi complex of more mature spermatocytes is characterized by an
      abundance of distinct stacks of cisternae interspersed with numerous vesicles and
      tubules. The composition of the Golgi complex was also studied by using two
      monoclonal antibodies that recognize either the cis or the trans Golgi cisternae,
      respectively, and employing biotin-streptavidin-peroxidase immunocytochemistry in
      5 micron frozen sections of testes. Immunodetection of the distinct cisternae
      revealed that the increase in size of the Golgi complex during maturation of
      pachytene spermatocytes was due predominantly to an accumulation of trans Golgi;
      the amount of cis Golgi remained unchanged. The morphological data presented in
      this study are consistent with an heightened secretory activity of pachytene
      spermatocytes during their maturation. In addition, the increase in size of the
      Golgi apparatus during the extensive prophase of pachytene spermatocytes may
      suggest that the mechanism employed by germ cells to partition the Golgi complex
      during the first division of meiosis varies significantly from that of somatic
      cells undergoing mitosis.

PMID- 1996782
TI  - Structural and immunohistochemical aspects of the postovulatory follicle in
      Japanese quail.
AB  - In the present study, we searched for the presence of granulosa lipid spheres, of
      lacunae, and of the smooth-muscle markers desmin and alpha-smooth-muscle actin,
      in the wall of the POF1 of the quail ovary. Lacunae, using the labelled yolk
      technique, were visible as large cavities in the POF1 wall. The
      immunohistochemical localization of desmin was similar to that observed in
      preovulatory follicles. A similar distribution was observed using an anti-alpha
      smooth-muscle actin antiserum, but the cells of the theca externa were also
      positively stained. The general conclusion was that the studied structures were
      similarly localized in the follicle wall, before and during the day after
      ovulation, but that they are more obvious in the POF, due to its general
      contracted state.

PMID- 1996783
TI  - Differential post-translational modifications of microtubules in cells of the
      seminiferous epithelium of the rat: a light and electron microscope
      immunocytochemical study.
AB  - The cells of the seminiferous epithelium of the rat testis are a rich source of
      microtubules and contain distinct microtubular structures such as the meiotic
      spindle and manchette. Microtubule diversity can be maintained by differential
      genetic expression of the multiple alpha- and beta-tubulin polypeptides or by
      tubulin monomer acetylation and detyrosination, post-translational modifications
      of alpha-tubulin. In the present analysis, antibodies that specifically recognize
      acetylated (antiacetylated), tyrosinated (anti-Tyr) and detyrosinated (anti-Glu)
      alpha-tubulins were employed to examine the distribution of post-translationally
      modified microtubules in the cells of the seminiferous epithelium. In the light
      microscope, a distinct pattern of staining for each antibody was detected using
      immunoperoxidase techniques on paraffin-embedded testicular sections. In the case
      of the anti-Glu antibody, a dense immunoperoxidase staining was detected in the
      cytoplasm of steps 4-7 spermatids. Thereafter, staining was noted over the area
      corresponding to the manchette of steps 8-15 spermatids, but not over their
      cytoplasm. The tails of spermatids were also reactive with this antibody. The
      anti-Tyr antibody was observed to be localized over the cytoplasm of Sertoli
      cells in their basal, supranuclear, and apical regions. A dense immunoperoxidase
      staining was also noted in the cytoplasm of pachytene spermatocytes, but it was
      negligible in the cytoplasm of spermatocytes undergoing their meiotic division;
      in these cells the centrioles and meiotic spindle were reactive. The spermatid's
      tails were also reactive. The antiacetylated antibody showed reactivity only over
      the tails of spermatids. With the electron microscope, a similar pattern of
      labeling was noted using immunogold labeling on Lowicryl K4M embedded testicular
      sections. The anti-Glu antibody heavily labeled microtubules of the manchette and
      the axoneme of tails of spermatids as well as microtubules of the proximal and
      distal centrioles and centriolar adjunct. The anti-Tyr antibody strongly labeled
      microtubules of Sertoli cells and the meiotic spindle and midbody of dividing
      spermatocytes. The anti-Tyr antibody also labeled the microtubules of the
      axoneme, centrioles, and centriolar adjunct of spermatids, but to a lesser degree
      than the anti-Glu antibodies; the manchette was faintly labeled. Of the three
      antibodies, the antiacetylated antibody showed the weakest labeling of
      microtubules of the centrioles, centriolar adjunct, and midbody, whereas those of
      the manchette and Sertoli cells were unreactive; the axoneme was moderately
      labeled.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1996784
TI  - Ontogenic appearance of three fatty acid binding proteins in the rat stomach.
AB  - With the use of specific antibodies against three structurally different fatty
      acid binding proteins (FABPs), viz, liver FABP (L-FABP), heart FABP (H-FABP), and
      intestinal FABP (I-FABP), the localization and relative amount of the
      immunoreactive proteins were determined by immunoblotting and immuno
      cytochemistry in the gastric epithelium of rats during prenatal and postnatal
      development. H-FABP immunoreactivity was first detected at embryonic day 20
      (E20), with predominant localization in the parietal cells, whereas I-FABP
      immunoreactivity was detected at the day of birth in the surface mucous cells.
      Both immunoreactivities were continuously localized in the same cell types with
      increasing intensity into adulthood. In contrast, the immunoreactivity for L-FABP
      showed remarkable changes in intensity and localization during development of the
      rat stomach. It was first detected in the surface mucous cells of E19. In the
      first 2 weeks of postnatal life, i.e., the suckling period, L-FABP
      immunoreactivity reached a peak in intensity and was localized not only in the
      surface mucous cells, but also in some of the parietal cells, brush cells, and
      endocrine D cells. In the following few weeks of weaning, the reactivity of
      surface mucous cells and parietal cells disappeared, leaving only a small amount
      of total L-FABP immunoreactivity in the adult stomach, which was localized
      exclusively in the brush cells and D cells. These results revealed that the
      appearance of the three types of FABPs in the rat stomach is specific to cell
      types and developmental stages.

PMID- 1996785
TI  - Hamster airway at parturition: ultrastructure of the full-term fetal trachea and
      effects of parturition.
AB  - Limited studies have described the ultrastructure of trachea of late fetal and
      neonatal hamsters but the effects of parturition and the onset of breathing on
      structure have not been discussed. This study describes morphological features of
      ante- and post-partum tracheal mucosa and submucosa and contrasts these features
      in fetal and neonatal hamster siblings. Significant differences between these
      siblings are noted in tracheal cells interfacing the lumen. Such cells of the
      fetal animals usually possessed cytoplasm of medium electron density with
      cisternal rough endoplasmic reticulum (RER). Surface membranes of these cells
      possessed numerous microvilli. In contrast, corresponding cells of post-natal
      animals often had lucent cytoplasm with mostly tubular or vesicular RER. Surface
      membranes of these cells possessed microplicae (microridges). This study also
      considers characteristics of fetal and neonatal tracheal development including:
      lomasome-like structures in secretory cells; dichotomous forms of oligocilia in
      mucosal and submucosal cells; intramembranous particles of hemidesmosomes;
      particles and mitochondria associated with desmosomes; and affiliations of
      ciliary basal bodies with the cytoskeleton, cell membrane, and with endoplasmic
      reticulum.

PMID- 1996786
TI  - An ultrastructural, morphometric analysis of rabbit fetal lung type II cell
      differentiation in vivo.
AB  - Rabbit lung type II cell differentiation was evaluated by use of ultrastructural,
      morphometric techniques. Fetal lung epithelial cells decreased in size
      dramatically from day 19 to day 21 of gestation. Thereafter, the cell and
      cytoplasmic cross-sectional area declined gradually until the neonatal time
      point. The tall columnar cell shape characteristic of fetal lung epithelial cells
      at early stages of development became cuboidal by day 24 of gestation. The number
      of mitochondria per micron2 cytoplasmic area in presumptive alveolar epithelial
      cells and the mitochondrial volume density increased toward the end of gestation.
      The volume density of glycogen pools within fetal lung epithelial cells reached a
      plateau on day 21 of gestation and then declined sharply on day 26 of gestation
      in lamellar body-containing, type II epithelial cells. Lamellar bodies increased
      in number and volume density in epithelial cells starting on day 26 of gestation
      and peaked with respect to these parameters in the neonatal lung tissue.
      Multivesicular bodies, which are thought to be a precursor to the lamellar body,
      became more prominent in differentiated type II cells on day 26 of gestation and
      increased in volume density from day 28 of gestation to the adult time point. The
      distance between mesenchymal and epithelial cells in fetal lung tissue declined
      sharply between days 24 and 26 of gestation but remained relatively constant
      thereafter. Foot processes extending from connective tissue cells contiguous to
      the epithelium were generally more numerous than those extending from the basal
      plasma membrane of epithelial cells at every stage of development examined. These
      data quantitate for the first time key ultrastructural events that occur during
      the differentiation of fetal lung epithelial cells in vivo.

PMID- 1996787
TI  - Endotoxin-induced endothelial injury and subendothelial accumulation of
      fibronectin in rat aorta.
AB  - Endotoxin (lipopolysaccharide, LPS) induces endothelial injury in arterial
      vessels. Fibronectin is known to be involved in cell attachment and wound repair.
      The present study was designed to elucidate the effect of LPS on the production
      and distribution of fibronectin in relation to injury and repair in rat aortic
      endothelium. Male Sprague-Dawley rats were sacrificed for ultrastructural and
      immunocytochemical evaluations at 1, 3, 6, 24, and 48 hr after a single
      intravenous injection of 1.5 or 3 mg/kg body weight E. coli LPS. Apparent
      morphological signs of endothelial injury, including cell detachment, denudation,
      cell death, and edema were observed 1-48 hr after injection. Parietal thrombosis
      and leukocyte diapedesis were also observed in the aorta. A profound increase in
      subendothelial fibronectin was found following LPS treatment. However, no
      distinct change in intracellular fibronectin was observed in the same endothelium
      until 24 hr after injection. Using horseradish peroxidase (HRP) and anti
      fibronectin-HRP antibody as tracers, LPS was also found to increase permeability
      and extravasation of plasma proteins (fibronectin) of the aortic endothelium. The
      increase of subendothelial fibronectin possibly resulted from increased influx
      and sequestration of plasma fibronectin. This increase may provide a firm
      substratum for reendothelialization after vascular injury.

PMID- 1996788
TI  - Turnover of asymmetric unit membranes in the transitional epithelial superficial
      cells of the rat urinary bladder.
AB  - Asymmetric thick unit membranes were observed on the luminal surface, fusiform
      vesicles, and multivesicular bodies of superficial cells of rat transitional
      epithelium. When HRP-labeled Ricinus communis lectin (RCA-I) was injected into
      the rat urinary bladder, RCA-I was deposited along the luminal cell membrane and
      in some multivesicular bodies, but not in the fusiform vesicles either before or
      after contraction. When the bladder was sliced by Vibratome and stained with HRP
      labeled RCA-I after fixation, RCA-I was observed in many cell organelles,
      including fusiform vesicles and multivesicular bodies as well as the luminal
      surface. When small pieces of tissue were stained en-bloc with HRP-labeled RCA-I,
      RCA-I was found along the luminal cell surface but not in the fusiform vesicles
      nor the multivesicular bodies. When HRP alone was injected into the bladder, HRP
      was observed in some multivesicular bodies after contraction but not in the
      fusiform vesicles. Various lysosomes were observed by electron microscopy. Some
      were wrapping multivesicular bodies in ringlike fashion, and some contained
      asymmetric unit membranes. These findings suggest that the asymmetric unit
      membranes are carried to the luminal cell membrane via the fusiform vesicles and
      that old luminal cell membranes are removed via the multivesicular bodies to be
      degraded by lysosomes.

PMID- 1996789
TI  - Flexion-extension views in the evaluation of cervical-spine injuries.
AB  - STUDY OBJECTIVE: To determine the efficacy of flexion-extension (F/E) cervical
      spine radiographs in detecting acute cervical-spine instability in emergency
      patients. DESIGN: We retrospectively reviewed the charts of 141 consecutive
      trauma patients who had F/E views performed after a routine cervical-spine series
      (three views) was obtained in the emergency department. Interpretations of the
      routine series were compared with those of the F/E views to determine if
      additional useful information was provided by the latter. The charts also were
      reviewed to determine if any variables were associated with an increased use of
      F/E views, an increased likelihood of these views demonstrating instability, or
      any neurologic sequelae resulted from these studies. SETTING: An urban Level I
      adult trauma center. MEASUREMENTS: The interpretations of the routine series were
      noted to be either normal, abnormal but without demonstrable
      fracture/dislocation, or demonstrating a fracture/dislocation. The F/E views were
      categorized as stable, unstable, or uninterpretable. RESULTS: Cervical-spine
      instability was demonstrated by F/E views in 11 of the 141 patients (8%), four of
      whom had normal routine cervical-spine films. Three of these four patients
      required surgical stabilization. Prolonged neck pain (more than 24 hours), an
      initially abnormal spine series, and a neurosurgical consult were all associated
      with an increased use of F/E views. Ten of 11 patients with radiographic
      instability had significant neck pain by history; the remaining patient was
      intoxicated. No neurologic sequelae resulted from performing F/E studies. There
      was one false-negative F/E study, which raises concern about the reliability of
      this procedure in the ED. CONCLUSION: We believe that a large prospective study
      is required to determine which patients warrant F/E views.

PMID- 1996790
TI  - Boehler's angle: a reappraisal.
AB  - STUDY OBJECTIVES: To reappraise Boehler's angle and evaluate factors, including
      centering of the central beam, sex of subjects, and side of the body, that may
      affect angle measurement. DESIGN: Retrospective clinical review. SETTING:
      Emergency department, Level I trauma center. TYPE OF PARTICIPANTS: 120
      consecutive patients radiographed for ankle injury who had normal bones on the
      ankle and/or foot radiographs. MEASUREMENTS AND MAIN RESULTS: The mean and SD of
      Boehler's angle were 30 degrees C +/- 6 degrees (range, 14 degrees to 50
      degrees). There was no difference in Boehler's angle between male and female
      subjects (P greater than .05) or between left and right feet (P greater than
      .05). Slight variations in central beam location for ankle and foot radiographs
      had no significant effect on Boehler's angle. CONCLUSION: If 28 degrees is taken
      as the lower limit of normal for Boehler's angle, 37 cases (31%) would be false
      positive "abnormal." The use of 20 degrees as the lower limit may decrease the
      number of false-positive to three cases (2.5%); using 18 degrees (mean -2 SD)
      reduces the false-positive rate to less than 1% (one case).

PMID- 1996791
TI  - Treatment of decompensated chronic obstructive pulmonary disease in the emergency
      department--correlation between clinical features and prognosis.
AB  - STUDY OBJECTIVE: Patients with decompensated chronic obstructive pulmonary
      disease (COPD) are at high risk of relapse after treatment in an emergency
      department. The purpose of this study was to determine if the risk of relapse
      correlates with the clinical features of the disease. PATIENTS: Three hundred
      fifty-two patients with documented COPD who were treated for dyspnea in the ED of
      the Albuquerque Veterans Administration Medical Center over a three-year period.
      METHODS: We reviewed the clinical features and pulmonary function tests of the
      patients, who were considered to have COPD if the baseline prebronchodilator one
      second forced expiratory volume (FEV1) was less than 80% predicted, and less than
      80% of the forced vital capacity and inhaled bronchodilators failed to increase
      the FEV1 to levels of more than 80% predicted. Visits for pneumonia,
      pneumothorax, pleural effusion, or pulmonary emboli were excluded. A relapse was
      defined as an unscheduled revisit to the ED within 14 days of initial treatment.
      Data were entered into a microcomputer data base and analyzed by a commercial
      statistical package. RESULTS: Of 877 visits in which the patient was treated and
      released from the ED, 281 (32.0%) resulted in relapse and were considered
      unsuccessful Compared with successful visits, unsuccessful visits were
      characterized by a shorter duration of dyspnea (P = .002), a lower entry FEV1 (P
      = .027), a lower discharge FEV1 (P = .040), a greater number of treatments with
      nebulized bronchodilators (P = .009), more frequent use of parenteral adrenergic
      drugs (P = .006), and less frequent use of oral prednisone on discharge (P =
      .016). Patients with one or more relapse visits during the study period
      (relapsers) differed from nonrelapsers in several respects. Relapsers had a
      greater bronchodilator response on baseline FEV1 than nonrelapsers (P = .047).
      Nevertheless, relapsers required more bronchodilator treatments in the ED (P less
      than .001); were treated more frequently with parenteral adrenergic drugs (P less
      than .001), IV glucocorticoids (P less than .001), and oral prednisone (P less
      than .001); and recovered less of their baseline FEV1 (P less than .014).
      CONCLUSION: Bronchodilator response on baseline pulmonary function testing
      appears to identify patients with COPD who have a poor prognosis after emergency
      treatment. Their poor response to intensive bronchodilator treatment suggests
      that loss of bronchodilator response may be involved in the pathogenesis of
      respiratory decompensation.

PMID- 1996792
TI  - Impact of portable pulse oximetry on arterial blood gas test ordering in an urban
      emergency department.
AB  - STUDY OBJECTIVE: To determine the impact of portable pulse oximetry on physician
      use of arterial blood gas tests (ABGs) in an urban emergency department. DESIGN:
      Prospective, controlled clinical trial. SETTING: The ED of the Regional Medical
      Center at Memphis, a publicly subsidized, 450-bed, acute care hospital staffed by
      residents and faculty of the University of Tennessee, Memphis. TYPE OF
      PARTICIPANTS: Rotating housestaff treating adult ED patients with a wide variety
      of medical and surgical problems. INTERVENTION: Introduction of a portable pulse
      oximeter for noninvasive measurement of blood oxygenation. MEASUREMENTS: Rates of
      ABG test ordering, housestaff reason(s) for ordering an ABG, and the incidence of
      adverse clinical outcomes before and after introduction of portable pulse
      oximetry. MAIN RESULTS: A total of 20,120 patient visits occurred during the four
      month study. Before oximeter introduction, emergency physicians ordered 699 ABGs,
      63% of which were indicated by explicit criteria. After oximeter introduction,
      440 ABGs were ordered (a 37% decrease). Almost all of this decrease was due to
      fewer ABGs ordered to assess oxygenation (260 before vs 75 after; chi 2, P less
      than .001). These reductions were not explained by differences in total patient
      visits or case mix. Physicians decreased ordering of indicated ABGs by almost as
      great an extent as they reduced ordering of unindicated tests, suggesting they
      did not consistently distinguish between the two. However, decreased testing did
      not result in any serious adverse outcomes, defined as unanticipated respiratory
      or cardiac arrest in the ED, unanticipated arrest on the floor within 24 hours of
      admission, or death within two days of hospital discharge. CONCLUSION: Portable
      pulse oximetry can provide a simple, noninvasive way to determine oxygen
      saturation in the ED. Routine use of portable pulse oximetry may substantially
      reduce rates of ABG testing and associated patient charges without adversely
      affecting the quality of emergency care.

PMID- 1996793
TI  - Lidocaine potentiation of cocaine toxicity.
AB  - STUDY HYPOTHESIS: The toxic effects of cocaine are enhanced in the presence of
      lidocaine. STUDY POPULATION: Male Sprague-Dawley rats weighing 200 to 300 g.
      METHODS: Animals received intraperitoneal injections of cocaine (10, 20, 35, or
      50 mg/kg), lidocaine (30 or 40 mg/kg), or a combination of all doses of cocaine
      given simultaneously with 30 or 40 mg/kg lidocaine. The incidence and time to
      seizure and death were recorded in these groups and compared by chi 2 and
      analysis of variance analyses, respectively. RESULTS: At doses of 30 or 40 mg/kg,
      lidocaine does not induce seizures or death. The effect of simultaneous injection
      of both cocaine and lidocaine was to dramatically increase the incidence of both
      seizures and death over that of cocaine alone. The incidence of seizures in
      animals receiving 35 mg/kg cocaine alone was 10%; this increased to 50% and 80%
      with the addition of 30 and 40 mg/kg lidocaine, respectively (P less than or
      equal to .05; P less than or equal to .01). Death did not occur in animals
      receiving 35 mg/kg cocaine alone; the addition of 30 and 40 mg/kg lidocaine
      resulted in death in 30% and 60% of animals, respectively (P less than or equal
      to .01 each group). Similarly, in rats receiving 50 mg/kg cocaine, the incidence
      of death increased from 0% to 60% and 80% with 30 and 40 mg/kg lidocaine,
      respectively (P less than or equal to .01). CONCLUSION: In the rat, overall
      toxicity of cocaine is significantly increased with simultaneous exposure to
      lidocaine.

PMID- 1996794
TI  - Phenytoin administration by constant intravenous infusion: selective rates of
      administration.
AB  - STUDY OBJECTIVES: To determine the adequacy of seizure control and the adverse
      effects of administering an IV loading dose of phenytoin by constant infusion
      pump. DESIGN: A prospective study of patients presenting with acute onset of
      seizures. Patients were divided into two groups. Group 1 comprised all patients
      50 years of age or younger without a history of atherosclerotic cardiovascular
      disease (ASCVD). Group 2 comprised all patients older than 50 years or with a
      history of ASCVD. SETTING: A rural community hospital emergency department. TYPE
      OF PARTICIPANTS: Forty-two adult patients. INTERVENTIONS: Both groups received an
      IV loading dose of phenytoin at 15 mg/kg. Infusion rates were 50 mg/min and 25
      mg/min for groups 1 and 2, respectively. Cardiac rhythm and vital signs were
      monitored throughout and after infusion. MEASURES AND MAIN RESULTS: Group 2
      demonstrated significantly more cardiovascular side effects (hypotension and
      bradycardia) than did group 1 (Fisher's exact test, P less than .05). CONCLUSION:
      Phenytoin provided adequate seizure control in both groups. For individuals with
      ASCVD, IV phenytoin administration rates should not exceed 25 mg/min. For
      individuals without ASCVD, phenytoin administration at 50 mg/min appears safe and
      without significant cardiovascular side effects.

PMID- 1996795
TI  - The adsorption of salicylates by a milk chocolate-charcoal mixture.
AB  - STUDY OBJECTIVE: To evaluate the adsorptive capacity of a milk chocolate-charcoal
      mixture to aspirin, compared with superactivated charcoal and conventional
      activated charcoal. DESIGN: A prospective, randomized, crossover study. SETTING:
      The Massachusetts Poison Control Center office in The Children's Hospital,
      Boston. TYPE OF PARTICIPANTS: Six healthy adult volunteers with no known
      allergies to aspirin or chocolate, bleeding disorders, or peptic ulcer disease.
      INTERVENTIONS: Each participant ingested 975 mg of crushed aspirin on separate
      days, followed by either water; 10 g milk chocolate-charcoal mixture; 10 g
      SuperChar Liquid; or 10 g Actidose Aqua activated charcoal. Total serum
      salicylate concentrations were determined by high-performance liquid
      chromatography at zero, one, two, four, eight, and 24 hours after ingestion.
      MEASUREMENTS AND MAIN RESULTS: Neuman-Keuls analysis was used to measure time-to
      peak concentration, which was reduced by SuperChar Liquid, 67%; milk chocolate
      charcoal mixture, 106%; and activated charcoal, 56%. Aspirin absorption was
      calculated using Neuman-Keuls analysis to measure area under the concentration
      time curve. Total aspirin absorption was reduced by SuperChar, 67%; milk
      chocolate-charcoal mixture, 50%; and activated charcoal, 2%. There was no
      difference in serum salicylate concentrations between SuperChar and milk
      chocolate-charcoal mixture at all time intervals. Also, all serum salicylate
      concentrations with milk chocolate-charcoal mixture were consistently lower than
      with activated charcoal. CONCLUSION: Although the formulation of milk chocolate
      with activated charcoal reduces its adsorptive capacity compared with
      superactivated charcoal, it is still able to bind aspirin effectively and is
      superior to conventional activated charcoal. Further research may improve the
      binding and palatability of milk chocolate-charcoal mixture, especially for home
      use.

PMID- 1996796
TI  - Use of clinical toxicology resources by emergency physicians and its impact on
      poison control centers.
AB  - STUDY OBJECTIVE: The need for clinical toxicology resources by emergency
      physicians is unclear and may have implications for future training and resource
      availability. This study was designed to assess current emergency physician use
      of available resources. DESIGN: Prospective evaluation by mail using a 49-item
      questionnaire. TYPE OF PARTICIPANTS: All 170 emergency physicians in Utah.
      INTERVENTIONS: None. RESULTS: The response rate was 75.3% (128 of 170). Resources
      "outside their own fund of knowledge" were consulted "occasionally" to
      "frequently" by 98.3%. They used the following resources "occasionally" to
      "frequently": poison control center (PCC) (93.7%), toxicology textbook (77.6%),
      "expert colleague" (34.0%), and "in-house POISINDEX" (23.9%). They often
      contacted the PCC for toxicity information (93.7%) and management recommendations
      (87.3%) and for acute, symptomatic overdose cases (88.3%). They "almost never"
      contacted the PCC for adverse drug reactions (76.6%), pill identification
      (70.2%), consultation with physician toxicologist (68.1%), asymptomatic exposures
      (62.9%), chronic toxicity (50.4%), or solely to report the case to the American
      Association of Poison Control Centers data base (90.2%). Those who had access to
      in-house POISINDEX often did not consult the PCC (82.6%). Of those who did not
      have in-house POISINDEX, 42.8% contacted the PCC to access it. Providing access
      to physician toxicologist consultations was thought to be an important role for
      the PCC by 86.7%, but only 32% of physicians were using this option. CONCLUSION:
      The vast majority of emergency physicians in Utah consult the PCC only for acute,
      symptomatic overdoses. They view access to physician toxicologist consultation as
      an important role for the PCC but seldom use it. The availability of in-house
      POISINDEX decreases the likelihood of PCC consultations from emergency
      departments. The frequency of emergency physician consultation with the PCC may
      decrease as POISINDEX becomes available at more hospitals.

PMID- 1996797
TI  - Toxicology screening of the trauma patient: a changing profile.
AB  - STUDY OBJECTIVES: To determine the current ingestants found in the multiply
      injured trauma patient and to determine if this select group of ingestants
      affected the resuscitation, evaluation, or convalescent management of these
      patients. DESIGN: A one-year retrospective analysis was performed on all patients
      who were admitted to an urban trauma center with a discharge diagnosis of
      multiple trauma and who received a comprehensive toxicology screening test. MAIN
      RESULTS: One hundred twenty-seven of the 177 patients (72%) who fulfilled the
      criteria had positive toxicology screens. Ethyl alcohol was the only drug present
      in 26 of these patients (20%); 57 (45%) were positive for drugs other than ethyl
      alcohol. A combination of ethyl alcohol and at least one other drug was
      quantified in 44 patients (35%). The most often encountered substances were ethyl
      alcohol (55%), marijuana (24%), and cocaine (21%). Twelve drug screens (9%)
      demonstrated pharmaceuticals (eg, acetylsalicylic acid, acetaminophen, or cyclic
      antidepressants) that may require specific antidotal treatment. CONCLUSION: The
      ingestant profile found in this subgroup of trauma patients differed from those
      of previous studies. Although a select group of these ingestants requires
      specific treatment or affects the physical assessment of the patient, none of
      these trauma patients received more than supportive care.

PMID- 1996798
TI  - Incidence of cocaine-associated rhabdomyolysis.
AB  - STUDY HYPOTHESIS: Rhabdomyolysis is a common complication of cocaine use, and
      muscle symptoms fail to predict its development. STUDY POPULATION: A prospective,
      convenience sample of patients presenting to the emergency department of a large
      inner-city hospital with complaints related to cocaine use were eligible for
      inclusion. Patients were excluded if they had other potential causes of elevated
      creatine kinase (CK) levels or rhabdomyolysis. A control group comprised patients
      who were not cocaine users and satisfied the exclusion criteria. Sixty-eight
      patients were studied. METHODS: Initial evaluation included determination of the
      presence of muscle pain or swelling and total CK levels. Patients with a CK level
      of more than 800 U/L had additional tests, including a urine myoglobin, urine
      drug screen, and serum phosphorus. Rhabdomyolysis was defined by a serum CK level
      of more than 1,000 U/L (more than fivefold that of normal). CK levels were
      compared by two-tailed Student's t test. Muscle symptoms were compared with the
      development of rhabdomyolysis by Fisher's exact test. RESULTS: The CK level in
      the cocaine group was 931 +/- 1,785 U/L (mean +/- 1 SD). The CK level in the
      control group was 242 +/- 168 U/L (P = .028). Of the cocaine users, 24% (eight of
      34) had rhabdomyolysis; one developed multiorgan failure and died. No patient in
      the control group had a CK level of more than 1,000 U/L. Only one cocaine user
      who developed rhabdomyolysis had muscle symptoms. Three cocaine users had muscle
      symptoms but did not develop rhabdomyolysis. No patient in the control group had
      muscle symptoms or developed rhabdomyolysis. Muscle symptoms did not predict the
      CK level (P = .55). CONCLUSION: This study revealed that 24% of the cocaine users
      had rhabdomyolysis. Many of the cases of rhabdomyolysis were not predictable from
      history or physical examination, making laboratory evaluation essential.

PMID- 1996799
TI  - China White epidemic: an eastern United States emergency department experience.
AB  - STUDY OBJECTIVE: The purpose of this study was to isolate significant clinical or
      demographic findings concerning overdose patients treated during a China White (3
      methyl fentanyl) epidemic and compare them with data for all unintentional
      narcotic overdose patients during a 24-month period. DESIGN: We reviewed charts
      from 85,246 patient visits to our emergency department during the 24-month period
      of January 1987 through December 1988 to study this narcotic epidemic. Data from
      the Allegheny County Coroner's Office pertaining to unintentional drug overdose
      deaths that occurred during this same period also were reviewed. SETTING: The
      first outbreak of narcotic overdoses in the eastern United States involving China
      White occurred in Allegheny County, Pennsylvania, in 1988. TYPE OF PARTICIPANTS:
      Patients were included if they met the criteria of a suspected unintentional
      narcotic overdose, but excluded if they were not given naloxone. INTERVENTIONS:
      Emergency physicians became suspicious of China White use after an unusual
      increase in narcotic overdoses presenting to the ED coupled with "routine drug of
      abuse" screens negative for opiates despite dramatic patient responses to
      naloxone. In most of the cases in which specific testing was done, there were
      positive indicators of fentanyl derivatives. Investigations found China White
      present in street drugs and paraphernalia. MEASUREMENTS AND MAIN RESULTS: A
      cluster was defined as a time period with a statistically significant increase in
      overdoses over the expected number for an interval of equal length. Although
      there were no significant clinical differences in case presentation during the 24
      month period, there was a statistically significant 13-fold increase in overdoses
      during the September through November 1988 cluster (mean, 13 vs 0.95 per month, P
      less than .001 by Wilcoxon rank-sum test). A dramatic increase in unintentional
      drug overdose deaths occurred in the county during this cluster. A total of 18
      fentanyl-positive unintentional drug overdose deaths, predominantly male (89%)
      and black (56%), with an age range of 19 to 44 years (mean, 34.9 years), were
      reported by the county coroner (13 during the cluster). Narcotic overdoses and
      unintentional drug overdose deaths declined sharply with confiscation of a
      clandestine China White laboratory. CONCLUSIONS: China White was responsible for
      a dramatic rise in unintentional drug overdose deaths in Allegheny County in
      1988. There were no significant clinical differences between China White overdose
      survivors and other unintentional narcotic overdose victims. Overdoses responsive
      to naloxone with inconsistent routine toxicologic screens may be due to a
      fentanyl analogue.

PMID- 1996800
TI  - The cardiovascular effects of cocaine.
AB  - Cocaine use and abuse continue to overwhelm urban economic, social, and health
      care systems. Patients frequently present to the emergency department with life
      threatening manifestations of cocaine use, including trauma, acquired immune
      deficiency syndrome, psychomotor agitation, and cardiovascular collapse. Adequate
      treatment of the cocaine-intoxicated patient requires a critical understanding of
      the risk-to-benefit ratios for pharmacologic, toxicologic, and surgical or
      obstetric interventions. The pharmacologic and physiologic bases for the vascular
      manifestations of cocaine toxicity and experimental evidence for treatment
      strategies are reviewed.

PMID- 1996801
TI  - A profile of BLS and ACLS instructors.
AB  - STUDY OBJECTIVE: To examine factors that motivate people to become and remain
      basic life support (BLS) and advanced cardiac life support (ACLS) instructors.
      DESIGN: A questionnaire was mailed to 967 BLS and ACLS instructors. SETTING: The
      study was performed in the San Francisco Bay Area. TYPE OF PARTICIPANTS: All BLS
      and ACLS instructors whose names were registered with the Santa Clara County
      Affiliate of the American Heart Association. RESULTS: Although there is room for
      improvement, 81% of the instructors were satisfied with their jobs. "Satisfaction
      in performing a valuable service" was the predominant reason they became
      instructors. "Lack of time" was the main factor causing people to stop teaching.
      CONCLUSION: The majority of BLS and ACLS instructors surveyed were quite happy.
      The current system appears to be working in that the teachers themselves are
      satisfied. An accurate portrait of BLS and ACLS instructors is crucial for
      organizations such as the American Heart Association if they wish to attract and
      retain instructors.

PMID- 1996802
TI  - Flumazenil: a new benzodiazepine antagonist.
AB  - Flumazenil is a recently discovered pharmacologic antagonist of the CNS effects
      of benzodiazepines. It acts by binding CNS benzodiazepine receptors and
      competitively blocking benzodiazepine activation of inhibitory GABAergic
      synapses. Animal studies and some human studies appear to demonstrate that
      flumazenil has weak intrinsic agonist activity; on the other hand, studies are
      inconclusive in demonstrating any inverse agonist effects of this agent. Evidence
      available suggests that flumazenil is well tolerated in human beings over a broad
      range of doses when given either orally or parenterally and does not produce
      serious adverse effects. In the setting of isolated benzodiazepine overdose,
      flumazenil is capable of completely reversing coma within one to two minutes,
      with this effect lasting between one and five hours. Repeat doses can be given
      safely to reverse recurrent effects of longer-acting benzodiazepines. Flumazenil
      is undergoing further evaluation by the Food and Drug Administration; should this
      drug receive approval, it is likely to be used in emergency departments as well
      as in a variety of other clinical settings. First, it could be used to effect
      rapid reversal of benzodiazepine-induced sedation that has been administered to
      facilitate medical, orthopedic, and surgical procedures, particularly in the
      event of inadvertent respiratory depression. Second, flumazenil might have a
      therapeutic role in the management of patients who have taken benzodiazepine
      overdoses. Although most of these patients can be managed successfully with
      supportive therapy alone, it is possible that the use of flumazenil may obviate
      the need for intubation and respiratory support in such patients and eliminate
      the possible adverse effects of even short-term endotracheal intubation. Finally,
      flumazenil could have both diagnostic and therapeutic value in patients with
      acute alterations of mental status of unknown etiology, particularly when
      possible drug overdose is a consideration. Because flumazenil appears to be
      specific in its antagonism of benzodiazepine-induced respiratory and CNS
      depression, it could be used empirically to confirm or exclude a role of
      benzodiazepines in the generation of mental status changes in the setting of
      overdose or coma of unknown origin. This in turn might obviate the need for
      further expensive (eg, computed tomography) and sometimes invasive (eg, lumbar
      puncture) diagnostic modalities. This might be particularly useful because there
      is nothing about benzodiazepine-induced coma that clearly distinguishes it from
      other causes of coma; thus, there are no signs or symptoms that may reasonably
      allow benzodiazepine overdose to be confirmed or eliminated on clinical grounds.
      Further studies will continue to define the ultimate use of this new agent.

PMID- 1996803
TI  - Ultrasound for the detection of foreign bodies.
AB  - STUDY OBJECTIVE: To determine the ability of an emergency physician to detect a
      variety of foreign bodies in an experimental model using a portable ultrasound
      device. DESIGN: Ten pieces of beef were sliced into cubes approximately 6 cm on
      each side. Six different groups of foreign bodies were examined: gravel, cactus
      spine, glass, metal, wood, and plastic. An independent observer placed the
      objects in a random fashion into the beef cubes. One hundred twenty observations
      were made using sets of ten beef cubes at a time. Five foreign bodies were placed
      into each set of ten beef cubes. INTERVENTIONS: A blinded emergency physician
      used a portable ultrasound with a 7.5-MHz transducer to determine the presence or
      absence of a foreign body in each cube. MEASUREMENTS AND MAIN RESULTS: Ultrasound
      detected 59 of 60 foreign bodies, including all cubes of meat embedded with
      gravel, cactus spine, plastic, metal, and wood. Glass was detected nine of ten
      times. Of the 60 cubes of meat with no foreign bodies, one false-positive was
      recorded. This yielded sensitivity, specificity, positive predictive value, and
      negative predictive value of 98%. Positive determinations by ultrasound were
      significantly greater in the meat cubes with foreign bodies compared with the
      control group with no foreign bodies (P less than .001 by chi 2). Although the
      subset of glass foreign bodies had one false-positive and one false-negative, it
      was not significantly different in comparison with the other groups (P greater
      than .05 by chi 2). CONCLUSION: Ultrasound has promise as a diagnostic tool for
      the detection of a variety of foreign bodies. Further clinical studies using
      ultrasound for the detection of foreign bodies are warranted.

PMID- 1996804
TI  - Cocaine-induced iritis.
AB  - The case of a 31-year-old man who presented to the emergency department with
      iritis from intranasal cocaine use is described. This was the second episode of
      iritis in this patient after casual cocaine use. The differential diagnosis of
      iritis and a proposed pathophysiologic mechanism are discussed.

PMID- 1996805
TI  - Drug-induced supraventricular tachycardia: a case report of fluoxetine.
AB  - We report the occurrence of supraventricular tachycardia and hypotension in a 54
      year-old woman after maintenance therapy with fluoxetine. Although cases of
      tachycardia and palpitations have been reported, supraventricular tachycardia and
      hypotension have not been directly attributed to fluoxetine.

PMID- 1996806
TI  - Torsades de pointes therapy with phenytoin.
AB  - We present the case of a woman with myocardial infarction complicated by
      malignant ventricular arrhythmia and torsades de pointes. The torsades de pointes
      was refractory to conventional therapy but responsive to phenytoin. This case
      suggests the clinical usefulness of phenytoin for adjunct therapy of life
      threatening ventricular arrhythmias when standard treatment modalities fail.

PMID- 1996807
TI  - Delayed onset of cardiac arrhythmias from sustained-release verapamil.
AB  - Sustained-release products in overdose are known to produce prolonged effects as
      well as delayed onset. The availability of sustained-release calcium channel
      blockers may produce an initial misleading picture for patients who are at risk
      for serious toxicity. We report the cases of two adults who had delayed onset of
      arrhythmias after ingestion of sustained-release verapamil. In both cases, a
      single dose of activated charcoal was administered, but the patients still
      developed toxicity. Some of the unique problems encountered with sustained
      release formulations are discussed, and 24-hour cardiac monitoring for sustained
      release calcium channel blocker overdoses, despite a possible early asymptomatic
      period, is suggested.

PMID- 1996808
TI  - Poisoning with equine phenylbutazone in a racetrack worker.
AB  - Phenylbutazone is a potent nonsteroidal, anti-inflammatory drug often used by
      veterinarians to treat racetrack animals. Its use in human beings is limited
      because of significant adverse effects and the availability of newer, safer
      drugs. We report the case of a 24-year-old man who ingested 17 g of equine
      phenylbutazone over a 24-hour period to treat the pain of a toothache. He
      developed grand mal seizures, coma, hypotension, respiratory and renal failure,
      and hepatic injury. Serum phenylbutazone concentration obtained approximately
      eight hours after presentation was 900 micrograms/mL. The patient recovered
      during six weeks of intensive supportive care and repeated hemodialysis.

PMID- 1996809
TI  - Multiple cranial nerve deficits after ethylene glycol poisoning.
AB  - We report the cases of two patients who developed cranial nerve palsies after
      drinking ethylene glycol. A 33-year-old man developed multiple cranial nerve
      deficits nine days after the ingestion of ethylene glycol in a suicide attempt.
      Clinical findings included profound bilateral cranial nerve VII palsies and
      severe dysfunction of cranial nerves IX and X. The neuropathy occurred despite
      treatment with hemodialysis. The dysphagia completely cleared within two weeks,
      but at six months a severe bilateral cranial nerve VII dysfunction persisted. A
      22-year-old man undergoing hemodialysis for ethylene glycol-induced renal failure
      developed bilateral cranial nerve VII dysfunction 14 days after ingestion. At a
      three-month follow-up, the patient demonstrated only moderate functional
      recovery. The etiology of the cranial nerve deficits is unknown but may be
      related to oxalate crystal deposition of ethylene glycol-induced pyridoxine
      dysfunction.

PMID- 1996810
TI  - Keeping American Heart Association ACLS standards and guidelines current.

PMID- 1996811
TI  - Buffered lidocaine.

PMID- 1996812
TI  - A case of spontaneous combustion.

PMID- 1996813
TI  - Confirmation of central venous catheter location.

PMID- 1996814
TI  - Estimation of myocardial ischemic injury during ventricular fibrillation with
      total circulatory arrest using high-energy phosphates and lactate as metabolic
      markers.
AB  - STUDY OBJECTIVE: To define the time course of myocardial ischemic injury using
      high-energy phosphate (HEP) depletion and the cessation of lactate production as
      metabolic markers. SETTING: Data were collected in a laboratory animal model.
      TYPE OF PARTICIPANTS: Ten immature mixed breed swine weighing 23.2 +/- 3.5 kg.
      DESIGN: After thoracotomy, transmural myocardial biopsies were taken in vivo
      during normal sinus rhythm and at designated times during ventricular
      fibrillation with total circulatory arrest (VF-TCA). MEASUREMENTS AND MAIN
      RESULTS: Frozen tissue samples were analyzed for adenine nucleotides, by high
      performance liquid chromatography, and lactate by enzymatic assay. At five
      minutes of VF-TCA, myocardial adenosine triphosphate averaged 50% of control. At
      15 minutes of VF-TCA, 89% of animals had myocardial adenosine triphosphate levels
      above 20% of control and adenylate charge ratio above 0.60. With more than 30
      minutes of VF-TCA, all animals had adenosine triphosphate levels below 10% of
      control and adenylate charge ratio below 0.30. In addition, myocardial lactate
      levels plateaued after 30 minutes of VF-TCA, indicating the cessation of lactate
      production. CONCLUSION: These results suggest that the myocardium can tolerate VF
      TCA for as long as 15 minutes without irreversible injury; however, post-ischemic
      myocardial dysfunction may occur after as little as five minutes of VF-TCA. With
      more than 30 minutes of VF-TCA, myocardial injury is likely to be irreversible.

PMID- 1996815
TI  - Comparison of two doses of endotracheal epinephrine in a cardiac arrest model.
AB  - STUDY OBJECTIVE: The objective of this study was to measure plasma catecholamine
      levels and the cardiovascular response before and after endotracheal
      administration of epinephrine in a swine cardiac arrest model. DESIGN:
      Prospective, controlled laboratory investigation. TYPE OF PARTICIPANTS: Twenty
      one swine weighing 10 to 12 kg, anesthetized with ketamine and alpha-chloralose
      and ventilated with room air. INTERVENTIONS: Ventricular fibrillation was induced
      with 90 V of 60 Hz current delivered to the right ventricle by transvenous
      pacemaker. Blood samples for epinephrine were drawn before arrest and every two
      minutes thereafter. At five minutes, external mechanical cardiac compressions
      were initiated. Nine animals received no further therapy and served as controls.
      Two groups of six animals received either 0.01 mg/kg or 0.1 mg/kg of epinephrine
      through the endotracheal tube at ten and 20 minutes. Blood samples were assayed
      for epinephrine. MEASUREMENTS: Arterial blood pressure, lead II ECG, and plasma
      epinephrine. MAIN RESULTS: Swine receiving epinephrine 0.01 mg/kg had an increase
      in epinephrine levels after drug administration, but these were not significantly
      different from control levels. The 0.1-mg/kg dose group had a significant
      increase in plasma epinephrine levels compared with controls and the 0.01-mg/kg
      dose group after receiving epinephrine at ten and 20 minutes. These increases
      were from 14 +/- 3 to 215 +/- 40 ng/mL (+/- SEM) at 12 minutes after arrest and
      from 151 +/- 56 to 402 +/- 80 ng/mL at 22 minutes after arrest. CONCLUSION: These
      data suggest that standard dosing of epinephrine through the endotracheal tube
      during arrest does not produce significant increases in plasma catecholamines or
      blood pressure. Epinephrine 0.1 mg/kg produces a significant increase in plasma
      epinephrine levels, but it is not sufficient to produce a significant change in
      blood pressure.

PMID- 1996816
TI  - Plasma concentrations of epinephrine during CPR in the dog.
AB  - STUDY OBJECTIVE: The purpose of this study was to evaluate whether the marked
      increase in the plasma concentrations of epinephrine during cardiopulmonary
      arrest and basic life support (BLS) could be due in part to decreased
      distribution and/or elimination. DESIGN AND INTERVENTIONS: Dogs were randomly
      assigned to undergo adrenalectomy or sham-operation. Some adrenalectomized
      animals received an epinephrine infusion. MEASUREMENTS AND MAIN RESULTS: In the
      seven sham-operated dogs, the plasma epinephrine concentrations increased
      markedly during BLS as expected. In the seven adrenalectomized dogs receiving a
      constant infusion of epinephrine, cardiopulmonary arrest and BLS induced a three
      to sixfold increase in plasma epinephrine concentrations, with an increase in the
      mean plasma epinephrine concentrations (calculated from the area under the curve)
      of 1.21 +/- 0.12 ng/mL (P less than .05). In the seven adrenalectomized dogs
      receiving a constant epinephrine infusion but not subjected to cardiopulmonary
      arrest, the plasma epinephrine concentrations remained stable. Finally, in the
      seven adrenalectomized dogs not receiving an epinephrine infusion, the mean
      plasma epinephrine concentrations during BLS (calculated from the area under the
      curve) increased only by 0.05 +/- 0.04 ng/mL, significantly less than in
      adrenalectomized dogs receiving an epinephrine infusion (P less than .01).
      CONCLUSION: The increase in plasma epinephrine concentrations during
      cardiopulmonary arrest and BLS is due in part to an altered disposition of
      epinephrine.

PMID- 1996817
TI  - Effect of intraosseous saline infusion on hematologic parameters.
AB  - STUDY OBJECTIVE: To examine the effects of intraosseous saline infusion on
      hematologic parameters. DESIGN AND SETTING: Eight New Zealand White rabbits were
      anesthetized with intramuscular ketamine. An initial blood sample was withdrawn
      from a earlobe vein on induction of anesthesia. An 18-gauge intraosseous needle
      was then inserted into the rabbit's proximal tibia, and 10 mL/kg of normal saline
      was infused over one minute. Two additional blood samples were obtained 15 and 30
      minutes after the intraosseous infusion. MEASUREMENTS: Complete blood counts were
      performed on the blood samples. RESULTS: Significant differences were found in
      monocytes, basophils, and nucleated RBCs from samples drawn before and after
      intraosseous infusion. The microscopic examination of the peripheral blood smear
      revealed an increase in the number of burr cells, schistocytes, and polychromasia
      in the postinfusion samples. CONCLUSION: We advocate caution in the
      interpretation of hematologic studies performed on blood samples obtained shortly
      after an intraosseous infusion.

PMID- 1996818
TI  - The empiric use of naloxone in patients with altered mental status: a
      reappraisal.
AB  - STUDY OBJECTIVE: To determine whether clinical criteria (respirations of 12 or
      less, mitotic pupils, and circumstantial evidence of opiate abuse) could predict
      response to naloxone in patients with acute alteration of mental status (AMS) and
      to evaluate whether such criteria predict a final diagnosis of presence or
      absence of opiate overdose as accurately as response to naloxone. CASES AND
      SETTING: Seven hundred thirty patients with AMS who received naloxone for
      diagnostic or therapeutic purposes at the discretion of two large, urban,
      paramedic base teaching hospitals. METHODS: We reviewed paramedic run sheets and
      audiotapes on all 730 patients as well as available hospital records of all
      patients who demonstrated any response to naloxone to determine whether overdose
      was responsible for their clinical presentations. We also reviewed hospital
      records for a selected sample of naloxone nonresponders. MAIN RESULTS AND
      CONCLUSION: Only 25 patients (3.4%) demonstrated a complete response to naloxone,
      whereas 32 (4.4%) manifested a partial or equivocal response. Nineteen of 25
      complete responders (76%), two of 26 partial responders (8%) (with known final
      diagnosis), and four of 195 non-responders (2%) (with known final diagnosis) were
      ultimately diagnosed as having overdosed. Respirations of 12 or less or the
      presence of any one of the three clinical findings as a group were each highly
      sensitive in predicting response to naloxone, and at least as sensitive as
      response to naloxone in predicting a diagnosis of opiate overdose. Selective
      administration of naloxone for AMS would have decreased the use of this drug by
      75% to 90% while still administering it to virtually all naloxone responders who
      had a final diagnosis of opiate overdose.

PMID- 1996819
TI  - Management of acute pyelonephritis in an emergency department observation unit.
AB  - STUDY OBJECTIVES: To determine whether moderately to severely ill patients with
      acute pyelonephritis can be treated successfully on an outpatient basis, and
      whether any aspect of history, physical examination, or initial laboratory data
      predicts failure of outpatient therapy and the need for hospitalization. DESIGN:
      Retrospective chart review of all patients with a diagnosis of acute
      pyelonephritis seen during a three-year period. SETTING: Emergency department
      observation unit of an urban teaching hospital serving residents of the city and
      county of Denver. TYPE OF PARTICIPANTS: Women between the ages of 15 and 50 with
      symptoms, physical examination, and initial laboratory data consistent with a
      diagnosis of pyelonephritis. INTERVENTIONS: Patients received IV antibiotics,
      rehydration, analgesics, and antiemetics in an observation unit for up to 12
      hours, when they were either admitted to the hospital or discharged home on oral
      antibiotics. MEASUREMENTS AND MAIN RESULTS: Sixty-three of 87 patients (72%) with
      acute pyelonephritis were managed successfully as outpatients, nine (22%) were
      hospitalized directly from the observation unit because they were considered to
      be too ill to go home, and five (6%) returned with persistent symptoms after ED
      therapy and were hospitalized. No clinical or laboratory variable predicted
      success or failure of ED observation unit therapy at the time of initial
      presentation. CONCLUSION: In selected patients, the observation unit may be used
      to initiate therapy for acute pyelonephritis. Those with an adequate clinical
      response to initial treatment may be discharged on oral antibiotic therapy with
      appropriate follow-up.

PMID- 1996820
TI  - Treatment of pyelonephritis in an observation unit.
AB  - STUDY OBJECTIVE: To determine the feasibility of managing patients with acute
      pyelonephritis as outpatients after initial treatment with IV antibiotics in an
      emergency department observation unit. DESIGN: Prospective and uncontrolled.
      SETTING: ED observation unit. TYPE OF PARTICIPANTS: Nonpregnant female patients
      14 years old or older without immunocompromise or serious underlying disease and
      no evidence of septic shock. INTERVENTIONS: All patients received two IV doses of
      trimethoprim/sulfamethoxazole at a 12-hour dosing interval and promethazine and
      acetaminophen as needed for nausea and fever, respectively. Baseline laboratory
      data, urinalysis, and urine and blood cultures were obtained. MEASUREMENTS AND
      MAIN RESULTS: Patients were observed for signs of septic shock, nausea, vomiting,
      and the ability to tolerate an oral intake. At the end of the observation period,
      43 of 44 patients were discharged on oral trimethoprim/sulfamethoxazole. One
      additional patient who was doing well clinically was recalled and admitted
      because of a positive blood culture. CONCLUSION: Patients with acute
      pyelonephritis, despite significant fever or nausea and vomiting, can be treated
      effectively as outpatients after a brief period of observation and IV
      antibiotics.

PMID- 1996821
TI  - HIV prevalence in a midwestern emergency department.
AB  - STUDY OBJECTIVE: To determine the prevalence of human immunodeficiency virus
      (HIV) seropositivity of patients 15 years of age and older in our emergency
      department. DESIGN: HIV status was determined anonymously, and the seroprevalence
      rate was calculated. The 95% confidence intervals also were calculated. Twenty
      demographic and predictor categorical variable were cross-tabulated with HIV
      status to determine associations. Only gender and male homosexual preference were
      significantly associated by Fisher's exact test. TYPE OF PARTICIPANTS: Excess
      serum samples from 454 randomly selected patients 15 years of age and older who
      required venipuncture for their ED evaluation were included in the study.
      MEASUREMENTS AND MAIN RESULTS: Of the 454 serum specimens, six (1.32%) were
      positive for HIV. The 95% confidence interval was from 0.27% to 2.37%. All six
      positive patients were men. The only statistically significant risk factors
      associated with HIV seropositivity were male sex (P = .00112) and male homosexual
      preference (P = .0000). CONCLUSION: HIV seropositivity occurs in 1.32% of our ED
      population over the age of 15 years. The only factors that correlate with HIV
      seropositivity are male homosexual preference and male sex.

PMID- 1996822
TI  - The physiologic response of CPR training.
AB  - STUDY OBJECTIVE: To determine the physiologic response of CPR training. DESIGN:
      Cardiovascular and ventilatory parameters were investigated during 40 minutes of
      CPR performance and during a maximum exercise test in seven female and nine male
      subjects (mean age, 30 years; range, 16 to 49 years). RESULTS: During CPR
      performance, mean oxygen consumption (0.36 +/- 0.10 L/min), and mean minute
      volume (21.9 +/- 6.0 L/min) were 16% and 26%, respectively, of the levels reached
      during a maximum exercise test. Systolic blood pressure (153 +/- 23 mm Hg) and
      heart rate (132 +/- 25 beats/min) were 75% and 73%, respectively, of the levels
      reached during a maximum exercise test. Serum lactate levels at rest and after
      CPR performance were not significantly different (1.08 +/- 0.99 vs 1.54 +/- 1.03
      mEq/L). Valsalva reflex remained present throughout total CPR time at varying
      degrees depending on individual differences in CPR technique (eg, incomplete
      extension of the manikin's head, holding the breath during chest compression).
      CONCLUSION: CPR performance seems to be a primarily aerobic effort that induces
      changes in cardiorespiratory parameters that were reasonably well tolerated by
      our study population.

PMID- 1996823
TI  - Aggression directed toward emergency department staff at a university teaching
      hospital.
AB  - STUDY OBJECTIVE: To determine the scope and magnitude of patient and visitor
      aggression directed toward emergency department staff. DESIGN: One-year
      retrospective review of university police log records and ED staff incident
      reports. SETTING: Medium-sized, urban, noncounty, university Level I teaching
      hospital treating approximately 40,000 ED patients annually. TYPE OF
      PARTICIPANTS: All violent incidents involving patients/visitors and ED staff that
      triggered a police response to the ED area were included in the study.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All ED violent episodes were
      recorded and categorized by shift, type of incident, type of police response,
      perpetrator, and site of incident. It was found that police responded to the ED
      nearly twice daily; the night shift had 32% of the cases with only 13% of the
      patient volume; custody and medical psychiatric clearance patients accounted for
      40% of the cases; more than 20% of incidents occurred in the waiting room; and
      4.2% of the incidents represented a significant threat to ED staff. CONCLUSION:
      ED violence is a significant and under-reported problem at our medium-sized
      university teaching hospital. These data are useful in objectively quantifying
      the scope of violence in our institution, and they underscore the potential risk
      to emergency patients, visitors, and staff. There is an acute need for additional
      studies in other settings so that appropriate and cost-effective security
      recommendations can be formulated.

PMID- 1996824
TI  - Critical decision making: managing the emergency department in an overcrowded
      hospital.
AB  - Hospital and emergency department overcrowding is a serious and growing problem
      nationwide. Although EDs are organized around the goals of rapid patient
      assessment, stabilization, and prompt admission to the hospital, an increasing
      number are being required to hold admitted floor and critical care patients for
      extended periods due to lack of vacant inpatient beds. Provision of acceptable
      patient care under such circumstances requires a fundamental reordering of ED
      priorities and procedures. Overcrowding is the result of inadequate funding for
      emergency health care services during a period of increasing demand. The initial
      focus of management strategies to resolve this problem is the inpatient area and
      includes evaluation of length of stay, "intent to discharge" policies, flexible
      bed designations, restriction of in-house transfers, and the use of "over-census
      beds." If in-hospital management strategies fail, modifications in ED management
      may include staffing contingency plans, definition of physician responsibility,
      inpatient charts, revised pharmacy formulary, new floor plans, and modified
      accounting systems. Successful resolution of hospital and ED overcrowding may be
      the greatest challenge facing emergency medicine today.

PMID- 1996825
TI  - Variability in thrombolytic practice in Oregon.
AB  - STUDY OBJECTIVE: To examine current thrombolytic protocols in Oregon emergency
      departments with regard to variations in patient evaluation, inclusion and
      exclusion criteria, initiation of therapy, and available thrombolytic agents.
      DESIGN: Telephone survey of ED head nurses. SETTING: All acute-care hospital EDs
      in Oregon. TYPE OF PARTICIPANTS: Of 70 acute-care hospitals contacted, 67 (96%)
      were included: 61 (87%) have a written ED protocol for thrombolytic agent use.
      METHODS: Telephone survey of written thrombolytic protocols, with comparison of
      groups using Kruskal-Wallis test (P less than .05). MEASUREMENTS AND MAIN
      RESULTS: The primary modes of initiating thrombolytic therapy are at the
      emergency physician's discretion (32%). after private physician consultation
      (24%), through the use of an agreement developed by the emergency physicians in
      conjunction with cardiologists or internists (22%), or after cardiologist or
      internist consultation (22%). ECG interpretation before drug administration is
      most often performed by the emergency physician (41%), cardiologist or internist
      (28%), private physician (6%), or computer (10%). Both tissue plasminogen
      activator (tPA) and streptokinase are available at 50 hospitals (75%); tPA is
      used exclusively in ten (15%) and streptokinase in seven (10%) other hospitals.
      tPA and streptokinase are approved for ED use in 43 (72%) and 46 (81%),
      respectively, of the hospitals at which these agents are available. In these, the
      ED is the most frequent site of administration of tPA in only 28 (65%) and of
      streptokinase in 33 (72%) hospitals; tPA and streptokinase are kept in the ED in
      only 23 (53%) and 23 (50%) of these hospitals, respectively. There was a
      significant correlation between thrombolytic administration in the ED and the
      number of full-time emergency physicians and American Board of Emergency Medicine
      diplomates. CONCLUSION: Thrombolytic protocols are highly variable in Oregon EDs.

PMID- 1996826
TI  - Use of emergency services by unaccompanied minors.
AB  - STUDY OBJECTIVE: The objective of the study was to describe the use of emergency
      services by minors who are unaccompanied by their parents or guardians and how
      they are managed in emergency departments. DESIGN: Self-administered survey. TYPE
      OF PARTICIPANTS: The ED directors of 71 emergency medicine training programs, 82
      Michigan community EDs, and 56 pediatric EDs. MEASUREMENTS AND MAIN RESULTS: One
      hundred eighteen (58%) surveys were returned. A median of five unaccompanied
      minors (range 0.2 to 150) were seen weekly by responding EDs. Pediatric EDs saw
      the most unaccompanied minors weekly (ten) compared with training programs (five)
      and community EDs (three) (P less than .01). Emergency medicine training programs
      had the greatest percentage (3.0%) of minors who were unaccompanied compared with
      pediatric EDs (2.2%) and community EDs (2.6%) (P less than .05). For all
      conditions surveyed, only 3.8% of patients would be refused medical care without
      parental consent. However, 36.8% of patients would have medical care delayed even
      for conditions that might be painful or harmful if left untreated for some time.
      Most EDs (85.5%) screen patients and treat those who are acutely ill, but some
      (11.1%) treat all regardless of severity. CONCLUSION: Protocols should be
      developed for unaccompanied minors to ensure that delays in obtaining consent do
      not jeopardize the child and that the rights of minors for confidentiality and
      consent are recognized.

PMID- 1996827
TI  - Tightening the screw: statutory and legal supervision of interhospital patient
      transfers.
AB  - A federal statute governing the transfer of indigent patients from Medicare
      enrolled hospitals was first enacted in 1986. Review of the statutory and other
      legal controls over interhospital transfers is precipitated by its recent
      amendment and the fining of a Texas physician for transferring a high-risk
      obstetric patient without following the statutory guidelines. These events are
      part of a pattern of increasing regulation of the practice of medicine.
      Physicians and hospital administrators responsible for hospital transfer policies
      should be aware of regulatory developments. Hospitals contemplating transfer of
      patients must develop transfer policies that comply with governing law, including
      state law. A transfer policy should provide guidelines as to when a patient is
      "stable for transfer". Patients may not be transferred unless a physician can
      certify that delay attendant to transfer will not be detrimental. Furthermore,
      the policy should specify the procedures to be followed to effect a transfer and
      any documentation that the physician will have to complete.

PMID- 1996828
TI  - Postpartum amaurosis.
AB  - Blindness is a rare but dramatic complication of pregnancy and delivery. We
      present the case of a patient who developed toxemia at the time of delivery that
      with ineffective treatment resulted in cortical blindness without seizure
      activity. The pathogenesis as well as the diagnostic workup and treatment of this
      unusual complication are discussed.

PMID- 1996829
TI  - Suddenly symptomatic brain tumors at altitude.
AB  - High-altitude cerebral edema can present with a wide variety of neurologic
      manifestations; these symptoms resolve with descent. The persistence of
      neurologic symptoms after descent suggests an intracranial lesion. Brain tumors
      suddenly becoming symptomatic at altitude have not been reported previously. We
      report three cases of previously unsuspected brain tumors that suddenly became
      symptomatic at high altitudes.

PMID- 1996830
TI  - The "fallen lung with absent hilum" signs of complete bronchial transection.
AB  - A 19-year-old pedestrian who was the victim of a motor vehicle accident had a
      left pneumothorax with a large air leak. Despite a well-placed chest tube, a
      chest radiograph showed that the left lung had fallen down and away from the
      mediastinum and that no hilar structures were visible. This "fallen lung with an
      absent hilum" is considered virtually diagnostic of complete mainstem bronchus
      transection.

PMID- 1996831
TI  - Common sense.

PMID- 1996832
TI  - The future of critical care medicine within emergency medicine.

PMID- 1996833
TI  - Acute dystonic reaction to crack cocaine.

PMID- 1996834
TI  - Crack cocaine-related epiglottitis.

PMID- 1996835
TI  - Management of hepatitis B.

PMID- 1996836
TI  - Screening for STDs.

PMID- 1996837
TI  - Nursing proposes health care reform.

PMID- 1996838
TI  - RNs bring needed services to rural areas.

PMID- 1996840
TI  - Resume is key to getting a job.

PMID- 1996839
TI  - Variety is spice for manager.

PMID- 1996841
TI  - Ethical, rights issues abound.

PMID- 1996842
TI  - Certification helps RNs achieve their goals.

PMID- 1996843
TI  - Air Force nurses in desert know how to make it work.

PMID- 1996844
TI  - Army nurses are ready for war.

PMID- 1996845
TI  - Navy RNs train for combat care.

PMID- 1996846
TI  - Does Desert Storm affect ANA priorities?

PMID- 1996847
TI  - Act addresses women's health.

PMID- 1996848
TI  - Liability--are you protected?

PMID- 1996849
TI  - Tailor liability insurance to meet your special needs.

PMID- 1996850
TI  - Medication errors expose RNs to liability.

PMID- 1996852
TI  - Rural America: a challenge equal to nursing's best.

PMID- 1996851
TI  - RNs must meet rural health care challenge.

PMID- 1996853
TI  - Program shows rural areas how to recruit RNs.

PMID- 1996854
TI  - These RNs are taking care of business.

PMID- 1996855
TI  - The glitter of everyday memory ... and the gold.

PMID- 1996856
TI  - Invited introduction: treatment of carcinoma of the oesophagus.

PMID- 1996857
TI  - Field surgery on a future conventional battlefield: strategy and wound
      management.
AB  - Most papers appearing in the surgical literature dealing with wound ballistics
      concern themselves with wound management in the civilian setting. The
      pathophysiology of modern war wounds is contrasted with ballistic wounds commonly
      encountered in peacetime, but it should be noted that even in peacetime the
      modern terrorist may have access to sophisticated military weaponry, and that
      patients injured by them may fall within the catchment area of any civilian
      hospital. Management problems associated with both wound types are highlighted;
      areas of controversy are discussed. The orthodox military surgical approach to
      ballistic wounds is expounded and defended.

PMID- 1996858
TI  - The role of reconstructive surgery in the management of war wounds.
AB  - Reconstructive surgery can be used within a framework of management of war wounds
      by basic principles. It falls into three groups: i. Primary (emergency)
      reconstruction; performed as part of initial surgery and as a life-saving
      procedure. ii. Delayed primary (essential) reconstruction; performed at the time
      of delayed closure. iii. Elective or non-essential reconstruction. All surgeons
      involved with the early management of war wounds should be prepared to perform
      primary and delayed primary reconstruction.

PMID- 1996859
TI  - Cetrimide lavage: ineffective and potentially toxic.

PMID- 1996860
TI  - Experience in the surgical management of medullary thyroid carcinoma.
AB  - The management of 12 patients with medullary thyroid carcinoma is reviewed. All
      patients underwent total thyroidectomy. Local nodal and extracapsular spread was
      aggressively resected, followed by radiotherapy. No patient died from
      uncontrolled local disease. Prolonged survival after radical treatment is
      demonstrated even in the presence of distant metastases.

PMID- 1996861
TI  - The use of computed tomography in the evaluation of large multinodular goitres.
AB  - This study reports one unit's experience of the value of computed tomography (CT)
      in the evaluation of 24 patients with large cervical and retrosternal goitres. Of
      these patients, 17 were thought clinically to have symptoms of tracheal
      compression, but the CT demonstrated significant narrowing in only 12 cases. In
      the other five patients, surgery was deferred and other causes for their symptoms
      sought and treated. Seven patients were asymptomatic and CT failed to reveal any
      evidence of tracheal compression in six. In the remaining patient, however, CT
      revealed gross narrowing and urgent surgery was performed. When compared with CT,
      chest/thoracic inlet radiographs were misleading in 48% of patients, with
      tracheal narrowing being overestimated and underestimated. We conclude that CT
      gives useful information about tracheal compression in patients with large
      multinodular goitres, and is more accurate than chest/thoracic inlet radiographs.

PMID- 1996862
TI  - Obesity surgery in the United Kingdom: survey of 970 general surgeons.
AB  - The results of a questionnaire survey on obesity surgery sent to 970 consultant
      general surgeons working in the United Kingdom National Health Service are
      presented. The response rate was 37%. There were 38 surgeons actively practising
      this surgery. The majority were performing a gastric procedure, mostly
      gastroplasty, but some did gastric bypass or banding. Three were doing the
      biliopancreatic bypass. Most surgeons were doing less than 10 operations a year.
      A total of 109 expressed an interest in attending a UK symposium and 59 would
      participate in a UK Bariatric Register. This practice, though only a small part
      of UK surgery, is larger than expected.

PMID- 1996863
TI  - Transcholecystic operative cholangiography: an alternative technique.
AB  - The current standard methods of carrying out operative cholangiography by
      cannulating the cystic duct or by direct puncture of the common bile duct are not
      without practical difficulties and potential hazards. An alternative method of
      introducing contrast material into the bile ducts for intra-operative imaging is
      described which is easy to perform, effective and safe. The technique consists of
      injecting contrast material into the previously emptied gallbladder and then
      propelling the contrast into the bile ducts by squeezing the viscus before taking
      X-ray films.

PMID- 1996864
TI  - Blood transfusion in total hip replacement: is it always necessary?
AB  - Routine blood transfusion was prospectively withheld from 10 patients undergoing
      routine elective total hip arthroplasty who fulfilled specific criteria. A
      standard anaesthetic regimen was used. The mean perioperative fall in haemoglobin
      concentration was 1.9 g/dl, and only one patient required a postoperative blood
      transfusion. There were no postoperative complications. The need for routine
      peroperative blood transfusion of patients undergoing total hip arthroplasty is
      questioned.

PMID- 1996865
TI  - Deaths following trauma: an audit of performance.
AB  - The TRISS methodology was applied to identify preventable trauma deaths in a
      retrospective audit of 267 (M = 0.908) patients admitted to a teaching hospital
      through the resuscitation room of its accident and emergency department during a
      1-year period. No unexpected survivors were identified; of the 44 deaths (Z =
      5.35), 25 (56.8%) were judged preventable by the TRISS method. Those deaths
      deemed preventable were subjected to peer review by a panel of six consultants.
      The findings are discussed in respect of recommendations made for UK trauma
      centre provision by the Working Party Report of the Royal College of Surgeons of
      England on the management of patients with major injuries.

PMID- 1996867
TI  - The response of general surgeons to HIV in England and Wales.

PMID- 1996866
TI  - Management of the chronic perineal sinus: not a problem to sit on.
AB  - It is our belief that the majority of cases of perineal sinus are curable if
      certain principles of wound management are followed. The causes and management of
      perineal sinus are reviewed. Four cases which illustrate the difficulties of
      achieving healing are reported, and from these important aspects of treatment are
      highlighted.

PMID- 1996869
TI  - McBurney's point--fact or fiction?

PMID- 1996868
TI  - A comparison of danazol and placebo in the treatment of adult idiopathic
      gynaecomastia: results of a prospective study in 55 patients.

PMID- 1996870
TI  - Aortocaval fistulas and the use of transvenous balloon tamponade.

PMID- 1996871
TI  - An MRC prospective randomised trial of radiotherapy versus surgery for operable
      squamous cell carcinoma of the oesophagus.
AB  - The objective of the trial was to determine whether there was any difference in
      survival rates after operable cases of squamous cell carcinoma of the oesophagus
      were treated by radiotherapy or surgery. It was designed as a prospective,
      randomised, multicentre trial in the United Kingdom, after staging as potentially
      operable, and it was planned to enter 100 patients per annum for 4 years, with a
      minimum follow-up of 5 years, after pre-entry staging of patients under 75 years
      of age by barium swallow, chest radiographs, oesophagoscopy, biopsy, bronchoscopy
      and CT scanning. The protocol was published in July 1986; the trial started in
      January 1987 and was stopped in June 1988 when only 31 patients from 16 centres
      were entered, although 30 centres had ethical committees' approval and were
      willing to start the trial. Interventions were to be as follows: 1. Surgery.
      According to the practice of that particular surgeon and classified as (a)
      curative resection if the surgeon considered that no macroscopic tumour was left
      behind, and (b) palliative if incompletely resected. 2. Radiotherapy. (a)
      Prescribed minimum corrected tumour dose of 5000 cGy with daily dose of 250 cGy
      in 20 fractions over 4 weeks. (b) Prescribed minimum corrected tumour dose of
      6000 cGy with daily dose of 200 cGy in 30 fractions over 6 weeks. The endpoint
      was to be survival at 1, 2 and 5 years. The trial was discontinued after 18
      months because of lack of recruitment and thus the question whether operable
      squamous cell cancer of the oesophagus, staged before treatment with CT scanning,
      is to be treated by radiotherapy or surgical resection remains unanswered. It is
      unlikely that a phase III trial will ever have sufficient support from surgeons
      to find the answer.

PMID- 1996872
TI  - Genetic cause of a juvenile form of Tay-Sachs disease in a Lebanese child.
AB  - Abnormality in the beta-hexosaminidase alpha gene underlying the clinical
      phenotype of a Lebanese patient with a juvenile form of Tay-Sachs disease has
      been studied. Clinical features were progressive spasticity, ataxia, and
      cognitive decline. The protein coding sequence of several beta-hexosaminidase
      alpha-chain complementary DNAs isolated by polymerase chain reaction was
      completely normal except for a G-to-A transition at nucleotide position 1511
      within exon 13, which resulted in substitution of the normal arginine 504 (CGC)
      with histidine (CAC). Although the patient was from a first-cousin marriage, she
      was heterozygous for this mutation. The abnormality in the other allele, which is
      carried by the father, was not identified, except that it is neither of the two
      mutations responsible for the infantile Jewish Tay-Sachs disease. Biosynthetic
      and immunoprecipitation studies in cultured fibroblasts showed synthesis of the
      alpha-chain precursor, but the mature form of the alpha-subunit was not detected.

PMID- 1996873
TI  - Excitatory amino acids in amyotrophic lateral sclerosis.

PMID- 1996874
TI  - Surgical treatment for infantile spasms?

PMID- 1996875
TI  - Elevated alpha-tumor necrosis factor levels in spinal fluid from HIV-1-infected
      patients with central nervous system involvement.
AB  - To assess the role of alpha-tumor necrosis factor in the pathogenesis of central
      nervous system involvement during human immunodeficiency virus type 1 infection,
      we recorded clinical data and measured alpha-tumor necrosis factor levels in
      serum and cerebrospinal fluid samples from 45 patients infected with human
      immunodeficiency virus type 1, classified as group II/III (10), group IV A (5),
      group IV B (10), and group IV C-1 (20) of the Centers for Disease Control
      acquired immunodeficiency syndrome classification system and 42 controls. Alpha
      tumor necrosis factor was above the limit of detection in only 3 of 15 sera and 3
      of 15 cerebrospinal fluid samples from patients in group II/III and group IV A,
      whereas it was detected in 17 of 30 sera (p less than 0.05) and 22 of 30
      cerebrospinal fluid (p less than 0.0002) samples from clinically more advanced
      patients (group IV B and group IV C-1). Alpha-tumor necrosis factor mean values
      were 21.5 pg/ml in sera and 50.0 pg/ml in cerebrospinal fluid from group IV B
      patients and 30.4 pg/ml in sera and 24 pg/ml in cerebrospinal fluid from group IV
      C-1 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1996876
TI  - Neuroanatomy of fragile X syndrome: the posterior fossa.
AB  - The occurrence and specificity of posterior fossa abnormalities as measured from
      magnetic resonance images of the brain were investigated in a group of 14 males
      with fragile X syndrome and comparison groups consisting of 17 males with other
      causes of developmental disability and 18 males with normal IQs. The size of the
      posterior cerebellar vermis was significantly decreased and the fourth ventricle
      significantly increased in the group of males with fragile X syndrome compared
      with males in both comparison groups. These neuroanatomical abnormalities
      appeared to be secondary to hypoplasia rather than atrophy.

PMID- 1996877
TI  - Magnetic resonance imaging and laboratory aids in the diagnosis of multiple
      sclerosis.

PMID- 1996878
TI  - Visual dysfunction in Alzheimer's disease: relation to normal aging.
AB  - In patients with Alzheimer's disease (AD), compared with age-matched and young
      healthy control subjects, visual deficits in the following functions were
      observed: color, stereoacuity, contrast sensitivity, and backward masking
      (homogeneous and pattern). Critical flicker fusion thresholds were normal,
      relative to age-matched healthy subjects. For color, the majority of the errors
      were tritanomalous (blue axis). Color and stereoacuity deficits were unrelated to
      severity of dementia, in accordance with models of vision that describe these
      functions as modular rather than diffuse for cortical localization. Although
      contrast sensitivity was depressed throughout the frequency range in AD, more
      patients were impaired at low than at high spatial frequencies, contrasting with
      the observed normal aging pattern of high-frequency loss. Healthy elderly
      subjects showed depressed critical flicker fusion thresholds and reduced contrast
      sensitivity at high frequencies, relative to the young group; differences between
      these groups were not found for the other vision tests. A subset of the AD group
      received detailed neuro-ophthalmological examination, and no abnormalities were
      found. This finding, taken together with normal thresholds for critical flicker
      fusion, suggests that the widespread visual dysfunction reported here is more
      likely to be related to known pathological changes in primary visual and
      association cortex in AD than to changes in the retina or optic nerve.

PMID- 1996879
TI  - Major differences in the dynamics of primary and secondary progressive multiple
      sclerosis.
AB  - In patients with primary and secondary progressive multiple sclerosis (MS), major
      differences in the pattern and extent of abnormality on cerebral magnetic
      resonance imaging (MRI) between the two groups have recently been demonstrated.
      In the present study, 24 patients, matched for age, sex, duration of disease, and
      disability, had serial gadolinium diethylenetriaminepentaacetic acid-enhanced MRI
      over a 6-month period. The 12 patients in the secondary progressive group had a
      total of 109 new lesions over this time (18.2 lesions per patient per year) and
      87% of these enhanced. Enhancement also occurred within and at the edge of
      preexisting lesions. In contrast, only 20 new lesions were seen in the primary
      progressive group (3.3 lesions per patient per year) and only one of these
      enhanced. There was no difference in the degree of clinical deterioration between
      the two groups over the 6-month period. These findings may indicate a difference
      in the dynamics of disease activity between the two forms of progressive MS,
      particularly in relation to the inflammatory component of the lesions, and have
      important implications for the selection of patients and the monitoring of
      disease activity in therapeutic trials.

PMID- 1996880
TI  - Correlation of phasic muscle strength and corticomotoneuron conduction time in
      multiple sclerosis.
AB  - Central motor conduction times for the adductor pollicis muscle, the twitch force
      of that muscle to scalp magnetic motor cortex stimulation, and the maximum force
      of phasic voluntary contraction of the same muscle were measured in 15 patients
      with multiple sclerosis. Two tests of manual dexterity of the same hand also were
      studied: the Purdue pegboard test, and the maximal frequency of a scissors
      movement of the thumb and index finger. The patients had normal strength or
      minimal weakness of the intrinsic muscles of the hand on clinical examination.
      The mean central motor conduction times for the adductor pollicis muscle for the
      patients were longer than normal, the peak twitch force of the adductor pollicis
      muscle evoked by cortical stimulation and the maximum force of a phasic voluntary
      contraction of the adductor pollicis muscle were smaller than normal. There were
      strong correlations between all these measures. Central motor conduction time in
      the patients was inversely correlated with voluntary phasic force and the twitch
      force after cortical stimulation. That is, the longer the central motor
      conduction time, the weaker the force. Prolonged central motor conduction time is
      likely to be accompanied by conduction block in corticomotoneuron pathways. The
      correlation of central motor conduction time with voluntary phasic force and the
      twitch force most likely reflects the degree of conduction block and temporal
      dispersion rather than delay in conduction per se. These results indicate that
      objective assessments of phasic muscle strength may reveal correlations with
      central motor conduction time that are not evident on conventional clinical
      examination which assesses tonic muscle contraction strength.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1996881
TI  - The functional anatomy of motor recovery after stroke in humans: a study with
      positron emission tomography.
AB  - We have studied regional cerebral blood flow changes in 6 patients after their
      recovery from a first hemiplegic stroke. All had a single well-defined
      hemispheric lesion and at least a brachial monoparesis that subsequently
      recovered. Each patient had 6 measurements of cerebral blood flow by positron
      tomography with 2 scans at rest, 2 during movement of fingers of the recovered
      hand, and 2 during movement of fingers of the normal hand. When the normal
      fingers were moved, regional cerebral blood flow increased significantly in
      contralateral primary sensorimotor cortex and in the ipsilateral cerebellar
      hemisphere. When the fingers of the recovered hand were moved, significant
      regional cerebral blood flow increases were observed in both contralateral and
      ipsilateral primary sensorimotor cortex and in both cerebellar hemispheres. Other
      regions, namely, insula, inferior parietal, and premotor cortex, were also
      bilaterally activated with movement of the recovered hand. We have also
      demonstrated, by using a new technique of image analysis, different functional
      connections between the thalamic nuclei and specific cortical and cerebellar
      regions during these movements. Our results suggest that ipsilateral motor
      pathways may play a role in the recovery of motor function after ischemic stroke.

PMID- 1996882
TI  - Lymphoma, motor neuron diseases, and amyotrophic lateral sclerosis.
AB  - We studied 9 patients with motor neuron disease and lymphoma. The following
      several observations have not been recognized in the past: (1) Motor neuron
      syndromes are associated with either Hodgkin's disease or non-Hodgkin's lymphoma.
      (2) The syndromes are not restricted to lower motor neuron disorders; 8 of 9
      patients had definite or probable upper motor neuron signs as well, qualifying
      for the diagnosis of amyotrophic lateral sclerosis. Corticospinal tracts were
      affected in both postmortem examinations. (3) The combination of motor neuron
      disease and lymphoma is often accompanied by paraproteinemia (3 of 7 patients
      studied), increased cerebrospinal fluid protein content (6 of 9 patients), and
      cerebrospinal fluid oligoclonal bands (3 of 9 patients). (4) In 2 patients,
      asymptomatic non-Hodgkin's lymphoma was found only because the discovery of
      paraproteinemia gave impetus to examine the bone marrow. (5) Patients with both
      upper and lower motor neuron signs (amyotrophic lateral sclerosis) may show
      physiological evidence of conduction block in peripheral nerves or autopsy
      abnormalities in peripheral nerves. The cause of this syndrome is not known. Both
      lymphoma and motor neuron disease could have a common cause, possibly a
      retroviral infection. The frequency of paraproteinemia suggests that an
      immunological disorder may play a role in the pathogenesis of the neurological
      disorder.

PMID- 1996883
TI  - Localization of 3H-dihydroergotamine-binding sites in the cat central nervous
      system: relevance to migraine.
AB  - Dihydroergotamine (DHE) is the treatment of choice in aborting the acute attack
      of migraine. Although its efficacy has been known for 40 years, its mechanism of
      action is still disputed. Data regarding the site of action of dihydroergotamine
      may provide an insight into its mechanism of action and thus identify a locus of
      potentially abnormal pathophysiology in migraine. By using in vitro and ex vivo
      autoradiographic techniques, the localization of specific binding sites for 3H
      dihydroergotamine in the cat brain has been examined. Binding was seen in the
      dorsal horn of the cervical spinal cord, in the medulla, associated with the
      nucleus of the tractus solitarius, area postrema, and descending spinal
      trigeminal nucleus, and in the mesencephalon and the cerebral cortex. The highest
      density of binding sites was found in the dorsal and medial raphe nuclei of the
      midbrain. Furthermore, these same brain regions were also labeled after
      intravenous administration of 3H-dihydroergotamine. It is important that the
      brain areas specifically labeled are key nuclei involved in cranial pain
      transmission, suggesting that dihydroergotamine may act at these central sites in
      migraine.

PMID- 1996885
TI  - Apparent response of subacute sclerosing panencephalitis to intrathecal
      interferon alpha.
AB  - An 8-year-old boy with subacute sclerosing panencephalitis (SSPE) was treated
      with 1.0 to 3.0 x 10(6) IU human interferon alpha (IFN) by the intrathecal route
      weekly or fortnightly. Pronounced improvement of clinical and
      electroencephalographic findings were observed in a dose-dependent manner. Our
      patient raises hope that IFN can induce sustained remission in patients with
      SSPE.

PMID- 1996886
TI  - Assisted reproduction and its implications for paediatrics.

PMID- 1996884
TI  - Acceleration of scrapie in trisomy 16----diploid aggregation chimeras.
AB  - We studied the susceptibility to prion infection of the trisomy 16----diploid
      chimeric mouse, a putative model of Down syndrome. When weanling chimeras were
      inoculated intracerebrally with scrapie prions, the time until appearance of the
      first symptoms of scrapie was reduced by 17 days (from a mean control time of 153
      days) and the time to death was reduced by 30 days (from control time of 170
      days). Our results with trisomy 16 chimeras argue that the susceptibility to
      central nervous system degeneration caused by prions can be modulated by
      chromosome imbalance.

PMID- 1996887
TI  - Cyclical variations in cerebral blood flow velocity.
AB  - Because little is known about spontaneous changes in cerebral blood flow in
      neonates, a newly developed online Doppler technique was used to insonate
      continuously the middle cerebral arteries of a group of sick (n = 20) and full
      term healthy (n = 16) newborn infants for a period of one minute. A total of 290
      recordings of epochs each lasting one minute were analysed, and pronounced
      regular, cyclical variations were seen in the velocity traces of these infants.
      The cycles occurred 1.5-5 times/minute and were present for at least one epoch in
      all 20 of the sick infants and in 15 of the 16 healthy mature neonates.
      Simultaneous recordings of the systemic blood pressure in the sick infants rarely
      showed the same cyclical variations. The cyclical variation is different from the
      beat to beat variability seen in the waveforms previously described, and is an
      additional factor to account for the wide variation in 'normal' velocity
      recordings obtained when Doppler ultrasound is measured over a short period of
      time.

PMID- 1996888
TI  - Neonatal screening for cystic fibrosis in Wales and the West Midlands: clinical
      assessment after five years of screening.
AB  - Screening of the newborn for cystic fibrosis by measurement of immunoreactive
      trypsin has been undertaken on alternate weeks in Wales and the West Midlands for
      five years since 1985 to evaluate the possible clinical benefits of early
      diagnosis. Patients detected by screening and those diagnosed by clinical
      symptoms alone were assessed annually for differences in clinical,
      anthropometric, and biochemical variables. Fifty eight infants not considered to
      be at risk of cystic fibrosis (they did not present with meconium ileus and do
      not have a sibling with cystic fibrosis) have been detected by screening and they
      have been compared with 44 children who were diagnosed clinically. This latter
      group includes nine children whose screening was negative but who were recognised
      subsequently to have cystic fibrosis. The mean age at diagnosis of the screened
      group was significantly lower than that of the group diagnosed clinically.
      Excluding admissions for diagnostic tests for cystic fibrosis, the screened group
      spent a significantly shorter time in hospital during the first year of life. The
      results of all other comparisons made between the screened group and those
      diagnosed clinically were similar up to the age of 4 years.

PMID- 1996889
TI  - Development of intestinal motility.

PMID- 1996890
TI  - Nutrition and bronchopulmonary dysplasia.
AB  - Twenty two babies who developed bronchopulmonary dysplasia were compared with 22
      babies matched for gestational age who did not. Those with bronchopulmonary
      dysplasia weighed less at birth and had lower energy intakes from day 7 to day
      56. Undernutrition before and after birth is a major problem in babies who
      develop bronchopulmonary dysplasia.

PMID- 1996891
TI  - Endotracheal resuscitation of neonates using a rebreathing bag.
AB  - Thirty asphyxiated neonates were resuscitated endotracheally with an anaesthetic
      rebreathing bag. The system was not limited either by pressure or by volume and
      chest movement was used as the criterion for adequate inflation. Inflation
      pressure and flow were recorded during resuscitation, and flow was integrated to
      obtain volume. Median mean pressure over the first 10 inflations was 40 cm H2O
      and this dropped during later resuscitation to 29 cm H2O. The volume delivered
      did not change significantly, so volume divided by pressure increased from a
      median of 0.18 to 0.35 ml/kg/cm H2O. Fourteen infants formed part of their
      functional residual capacity with artificial ventilation and five with
      spontaneous breaths. Eleven infants showed no evidence of functional residual
      capacity formation. In the 22 preterm infants there was a strong association
      between absence of functional residual capacity formation and later hyaline
      membrane disease that required ventilation. We suggest that pressures of more
      than than 30 cm H2O may be helpful during initial resuscitation and that there
      should be further study of devices using positive end expiratory pressure for
      resuscitation of preterm infants.

PMID- 1996892
TI  - Association of pneumothorax and hypotension with intraventricular haemorrhage.
AB  - To test the hypothesis that acute hypotension resulting from pneumothorax would
      be associated with severe brain injury (grade 3 or 4 intraventricular
      haemorrhage), 67 very low birthweight (VLBW) infants of 32 weeks' gestation or
      less with respiratory distress syndrome and pneumothorax were studied. Thirty six
      had pneumothorax associated with systemic hypotension and 31 had pneumothorax
      with normal blood pressure. The groups were similar in gestational age and
      severity of their respiratory distress syndrome. Thirty two of 36 of infants with
      pneumothorax associated with hypotension (89%) had grade 3 or 4 intraventricular
      haemorrhage. This percentage was significantly greater than the percentage for
      infants with pneumothorax and normal blood pressure (three of 31, 10%). The risk
      ratio for grade 3 or 4 intraventricular haemorrhage for infants with pneumothorax
      associated with hypotension was 9.8 compared with neonates with pneumothorax and
      normal blood pressure. These observations are consistent with the hypothesis that
      systemic hypotension and cerebral hypoperfusion are important factors leading to
      intraventricular haemorrhage in VLBW infants.

PMID- 1996893
TI  - Increased incidence of respiratory distress syndrome in babies of hypertensive
      mothers.
AB  - There is controversy over the effect of hypertension in pregnancy on the
      incidence of neonatal respiratory distress syndrome. We investigated the
      association between maternal hypertension and the incidence of respiratory
      distress syndrome in 268 very low birthweight babies of less than 34 weeks'
      gestation. A lower incidence of respiratory distress syndrome was associated with
      growth retardation and membrane rupture greater than 24 hours. Maternal
      hypertension was associated with an increased incidence of respiratory distress
      syndrome. We used the multiple logistic regression model to control for
      confounding variables, as the maternal and neonatal factors associated with
      respiratory distress syndrome were not evenly distributed between the two groups.
      After adjustment for birth weight, gestational age, growth retardation, and
      membrane rupture greater than 24 hours, the risk of developing respiratory
      distress syndrome was significantly greater in babies of hypertensive mothers.
      Significance was lost when labour before delivery and mode of delivery were taken
      into account. The increased incidence of respiratory distress syndrome in babies
      of hypertensive mothers may be due to the absence of labour before delivery
      because of the greater likelihood of caesarean section.

PMID- 1996894
TI  - Prolonged low dose indomethacin for persistent ductus arteriosus of prematurity.
AB  - A total of 121 infants who required indomethacin for persistent ductus arteriosus
      in Liverpool and Cambridge over a four year period were randomised to receive
      either 0.1 mg/kg daily for six days or 0.2 mg/kg every 12 hours for three doses.
      The groups were of similar birth weight and gestational and postnatal age, though
      those treated with a low dose were by chance receiving a higher percentage of
      oxygen at the start of treatment and there were more deaths from bronchopulmonary
      dysplasia in this group. Of 59 infants treated with the prolonged course 53 (90%)
      responded initially to indomethacin compared with 48 of 62 (77%) treated
      conventionally--a difference of 13% (95% confidence interval for the difference 0
      to 26%). Of the 53 responders 11 (21%) relapsed after low dose indomethacin,
      whereas after the shorter course 19 of 48 (40%) relapsed. This difference was
      significant (95% confidence intervals 3 to 37%). Side effects, mainly
      gastrointestinal haemorrhage, were similar in both groups. Significantly fewer
      infants experienced a rise in serum creatinine or urea concentration after
      treatment with low dose indomethacin. A prolonged low dose course of indomethacin
      offers advantages over conventional treatment.

PMID- 1996895
TI  - Light transmission measurements and phototherapy eyepatches.
AB  - The transmission characteristics of phototherapy eyeshields have been measured
      under conditions that mimic the clinical situation. Peak transmission (less than
      10%) was detected at 700 nm for the poorest patch tested and less than 2% for
      either of the other patches examined. The optics of measurement systems are
      considered with reference both to this and previous studies of light transmission
      through eyepatches. The simplicity and effectiveness with which eyepatches can be
      secured may be as important as their transmission characteristics.

PMID- 1996896
TI  - Doppler assessment of pulmonary artery pressure and extrapulmonary shunting in
      the acute phase of hyaline membrane disease.
AB  - The natural history of pulmonary artery pressure and extrapulmonary shunting in
      acute hyaline membrane disease was studied by serial Doppler echocardiography in
      57 preterm infants, 38 with, and 19 without, hyaline membrane disease. Pulmonary
      artery pressure was assessed non-invasively by its inverse relationship with the
      ratio of pulmonary artery Doppler time to peak velocity: right ventricular
      ejection time. The mean ratio was significantly lower in the infants with hyaline
      membrane disease. The mean ratio for each infant with hyaline membrane disease
      varied widely and did not correlate with criteria of maturity or severity of
      disease. Individual ratios correlated with arterial pH. Between 60-80 hours after
      birth, 14 of 18 infants with hyaline membrane disease (78%) and one of 19 without
      (5%) had patent ductus arteriosus. Left to right and bidirectional shunting at
      ductal and atrial level were common; pure right to left shunting was uncommon.
      The mean ratio seen with bidirectional shunting was significantly lower than that
      seen with left to right shunting. Ratios and patterns of extra pulmonary shunting
      were similar when the fractional inspired oxygen (FIO2) was greater than 0.9
      compared with when it was less than 0.9. Pulmonary artery pressure is high during
      the acute phase of hyaline membrane disease but varies widely among infants. A
      few infants have extrapulmonary right to left shunting, and these infants are
      difficult to detect clinically.

PMID- 1996897
TI  - Anticonvulsants in pregnancy.

PMID- 1996898
TI  - Resuscitation of the newborn.

PMID- 1996900
TI  - Treatment of persistent pulmonary hypertension of the newborn: update.

PMID- 1996899
TI  - Pathophysiology of apnoea in preterm infants.

PMID- 1996901
TI  - Francois Mauriceau (1637-1709) and maternal posture for parturition.

PMID- 1996902
TI  - In vitro response of the brown bullhead catfish cell line, BB, to aquatic
      pollutants.
AB  - Established cell lines from brown bullhead catfish (BB) and rainbow trout (RTG-2)
      and primary cultures of cells derived from gill, fin, and gonad tissues from
      brown bullhead catfish were evaluated for use as bioindicators in the neutral red
      cytotoxicity assay. The BB and RTG-2 cells were compared after a 1 day exposure
      to chlorinated pesticides and after a 6-day exposure to various polycyclic
      aromatic hydrocarbons. The BB cells were more sensitive to both classes of
      chemicals. The sequence of toxicity for the BB cells was 4,4'-DDD. 4,4'-DDT
      greater than aldrin, 4,4'-DDE and 7,12-dimethylbenz(a)anthracene (DMBA) greater
      than 3-hydroxybenzo(a)pyrene (3-OH-B(a)P) greater than benzo(a)pyrene (B(a)P).
      For the RTG-2 cells, the sequence was aldrin greater than 4,4'-DDD greater than
      4,4'-DDT greater than 4,4'-DDE and 3-OH-B(a)P greater than DMBA greater than
      B(a)P. The BB cells were also sensitive to benzo(b)fluoranthene,
      benzo(k)fluoranthene, benzo(a)anthracene, and trans-7,8-dihydro-7,8
      dihydroxybenzo(a)pyrene. The responses of BB and RTG-2 cells were compared with
      those of primary cultures after a 1 day exposure to B(a)P. After 1 day of
      exposure, the RTG-2 cells and primary cultures were more sensitive than the BB
      cells to B(a)P. Apparently, after 1 day of incubation the RTG-2 and primary cells
      metabolized greater amounts of B(a)P to cytotoxic metabolites, than did the BB
      cells. However, by 6 days of incubation, the BB cells were more sensitive to
      B(a)P than were the RTG-2 cells. A 6-day exposure to B(a)P was not performed with
      the primary cell cultures.

PMID- 1996903
TI  - Toxicity to estuarine organisms of leachates from chromated copper arsenate
      treated wood.
AB  - The effects of chromated copper arsenate (CCA), used for treating wood in docks,
      pilings, and bulkheads, were studied in several estuarine organisms. Leaching of
      metals from treated wood into sea water was assayed by atomic absorption
      spectrophotometry. Fiddler crabs (Uca pugilator) were subjected to limb removal
      and were placed in containers with treated wood of various sizes or control wood.
      Limb regeneration rate was retarded in a dose-dependent fashion and mortality
      occurred with the treated wood, reaching 100% in the tank with the largest piece
      of wood. Embryos of the mummichog (Fundulus heteroclitus) were allowed to develop
      in culture dishes in which CCA-treated or untreated wood was soaking. Mortality
      was noted in the dishes with treated wood and to a smaller extent in those with
      untreated wood. Containers containing CCA-treated wood, control wood, or no wood
      were stocked first with the alga Ulva lactuca, the snails (Nassarius obsoletus).
      Chlorophyll content of the algae was reduced with the treated wood within a few
      days, and snails with the treated wood became moribund and died within a few
      days. In the controls containing untreated wood or no wood, no such effects were
      seen. Studies with individual or combination of two or three of the metals with
      snails and algae indicated that the copper was primarily responsible for the
      snail mortality and algal bleaching seen in the treated wood experiments. In all
      experiments, the toxicity of the wood decreased over time; when the experiments
      were repeated with the same pieces of wood, effects were diminished.

PMID- 1996904
TI  - Cadmium concentrations in the freshwater mussel (Elliptio complanata) and their
      relationship to water chemistry.
AB  - Concentrations of cadmium were determined in freshwater mussels (Elliptio
      complanata) from 21 small lakes in south-central Ontario. The average Cd
      concentrations ranged from 0.5 to 7.5 micrograms/g dry weight. A poor correlation
      between the concentration of Cd in lakewater and the concentration of Cd in the
      organisms was observed. Concentration of Cd in the sediments was not a useful
      predictor. Thus, it is hypothesized that the availability of the Cd varies among
      the 21 lakes. In an effort to test this hypothesis, the relationships between
      organism concentrations and water chemistry parameters that have the potential to
      alter Cd availability including pH, calcium (Ca), total organic carbon (TOC) and
      total inorganic carbon (TIC) were examined. The strongest relationship was found
      between Cd concentration in the mussels and water column pH, suggesting that
      hydrogen ions are replacing Cd ions in complexes and increasing the amount of
      free Cd available to the organisms. Correlations between pH and other water
      chemistry parameters make it difficult to test this hypothesis. A multiple
      regression model was developed incorporating pH, Ca, TOC, and TIC which explained
      69% of the variance in Cd concentrations.

PMID- 1996905
TI  - Diversification of cadmium-binding proteins due to different levels of
      contamination in Arion lusitanicus.
AB  - Individuals of Arion lusitanicus were collected in the former mining area of
      Braubach (Federal Republic of Germany) which is highly polluted by various
      metals. The animals were transferred to the laboratory and fed contaminated
      litter from their original habitat. Groups of animals from a quarry near
      Heidelberg were reared in the laboratory and fed diets of different cadmium
      concentrations. Slugs fed uncontaminated food were used as controls. The
      concentration of cadmium in the midgut gland of cadmium-fed slugs increased in
      proportion with the metal concentration of the food. High amounts of zinc and
      copper were found in the midgut glands of slugs from Braubach. After
      centrifugation of homogenates, specific patterns of distribution between
      cytosolic components and pellets were observed for different metals. Cadmium and
      copper were predominantly bound to cytosolic components, whereas the main portion
      of zinc was associated with the pellet. In laboratory-fed slugs the increase of
      cadmium concentration in the food correlated with an increase of the metal
      content in the homogenate and in two components (supernatant, pellet) of the
      midgut gland. This correlation was most clearly expressed in the cytosolic
      components which contained 93-100% of total midgut gland cadmium. Total cadmium
      in control slugs was associated with components with a molecular weight of more
      than 15,000. In Braubach and in cadmium-loaded slugs, all the cadmium was bound
      to a protein with a molecular weight of 10,000, which also contained low amounts
      of zinc and copper. In highly contaminated individuals fed on the most
      concentrated cadmium diet, however, a spillover effect was observed, some cadmium
      being bound to an additional component with a molecular weight of more than
      15,000.

PMID- 1996906
TI  - Genetic damage in a population of slider turtles (Trachemys scripta) inhabiting a
      radioactive reservoir.
AB  - Turtles inhabiting a radioactive reservoir appear to experience genetic damage
      due to environmental exposure to low concentrations of long-lived radionuclides.
      Total body burdens for the 50 reservoir turtles examined in the survey ranged
      from 164.7-4679.3 Bq for cesium-137 and from 462.6-5098.3 Bq for strontium-90.
      Flow cytometric (FCM) assays of red blood cell nuclei demonstrated significantly
      greater variation in DNA content for the reservoir turtles than for turtles from
      a nearby, non-radioactive site. Furthermore, two of the reservoir turtles
      possessed FCM profiles that are indicative of aneuploid mosaicism. These data
      strongly suggest that exposure to low-level radiation may involve a sensitive
      genetic response in a natural population.

PMID- 1996907
TI  - Protection of human health from mixtures of radionuclides and chemical in
      drinking water.
AB  - This study was undertaken to develop a common scale for evaluating health risks
      from contaminated drinking water. For different agents, many unrealistic models
      of risk have been used. By intent, regulatory toxicology depends on "data-sparse,
      model-intensive" analogies from exotic animal genetics and novel exposures (NCRP
      1989). The question is, does a risk evaluation so derived have any predictive
      validity? Absence of data prevents answer because regulatory toxicology
      rationalizes in step-by-step logic, which we call absolute (i.e., predicts cases
      of disease in a population). Absolute models ensure safety, but do so at the cost
      of realism. In contrast, we make relative comparisons in the manner of horsepower
      or RBE from radiation biology. All pollutants are assumed to contribute to toxic
      injury. Next, relative potencies are linked to the most credible standards. Thus,
      experience is transferred from well-studied chemicals to the new chemical by
      "data-intensive, model-sparse" methods. This logos provides much relative
      precision. Then, pollutants are compared with: (1) common foodstuffs, (2) ambient
      radiation background, or (3) utility-pure drinking water. Finally, an assessment
      is made for a waste disposal area.

PMID- 1996908
TI  - The toxic effect of deltamethrin on linyphiid and erigonid spiders in connection
      with ambient temperature, humidity, and predation.
AB  - The first part of this study concerns the effect of temperature and air humidity
      on the toxicity of deltamethrin to the erigonid Oedothorax apicatus. The second
      part concerns the effect of deltamethrin on behavior of linyphiids and erigonids
      with respect to their ability to escape from predators and to select between
      unfavorable (dry) and favorable (moist) habitat conditions. The toxic effect of
      deltamethrin was highest at the combination of high temperature and low air
      humidity. It was concluded that the spider's sensitivity to drought is increased
      by this pyrethroid. Affected spiders, however, are less able to select moist
      habitat conditions than unaffected ones. Walking speed of spiders was decreased
      by exposure to deltamethrin and their predation by carabid beetles was increased.
      It was concluded that the effect observed under field conditions is the result of
      a combination of neurological, physiological, and behavioral disturbance.

PMID- 1996909
TI  - Brain acetylcholinesterase activity in forest songbirds exposed to a new method
      of UULV fenitrothion spraying.
AB  - Brain acetylcholinesterase (AChE) activity was measured in forest songbirds
      exposed to Ultra Ultra Low Volume (UULV) aerial spraying of fenitrothion in New
      Brunswick for spruce budworm control. Brain AChE activity was determined in 324
      songbirds from the sprayed blocks and 47 from an unsprayed control area, and
      represented four species. In most cases, more than half of the individuals of any
      species sampled were diagnosed as "exposed" (greater than or equal to 20%
      inhibition) to the fenitrothion sprays and had a mean percent level of inhibition
      of 40% or greater, relative to mean control values. The proportion of birds with
      life-threatening levels of inhibition (greater than or equal to 50%) was usually
      less than 20%. The largest proportion of birds with life-threatening inhibition
      was found after the first 210 g AI/ha spray. The White-throated Sparrow had the
      highest proportion (25-55%) of individuals with life-threatening inhibition after
      all sprays. Brain AChE inhibition was greater in exposed birds collected after
      the first 210 g AI/ha spray than after the second one. Variation among species'
      responses to the sprays is discussed in relation to habitat and foraging
      preferences. Several sampling biases which may contribute to underestimation of
      the impact of fenitrothion spraying on birds are identified.

PMID- 1996910
TI  - Productivity, diet, and environmental contaminants in bald eagles nesting near
      the Wisconsin shoreline of Lake Superior.
AB  - Bald eagles (Haliaeetus leucocephalus) nesting in the Apostle Islands National
      Lakeshore and along the Wisconsin shoreline of Lake Superior produced an average
      of 0.8 young/occupied nest and had an average nest success of 57% during 1983
      1988, compared to 1.3 young/occupied nest and 77% nest success in inland
      Wisconsin. Contaminant levels in nestling bald eagle carcasses collected from
      nests near Lake Superior were higher than those collected inland, suggesting
      local contamination. Prey remains collected at nests consisted of fish (50%);
      birds, primarily herring gulls (Larus argentatus) (48.4%); and mammals (1.2%).
      Organochlorine and polychlorinated biphenyl (PCB) residues were present at low
      levels (DDE: means = 0.07 micrograms/g wet wt, PCP: means = 0.21 micrograms/g wet
      wt) in fish. Herring gulls contained higher concentrations (DDE: means = 5.5
      micrograms/g wet wt, PCB: means = 16.95 micrograms/g wet wt) and appear to be the
      major source of elevated contaminant levels in bald eagles nesting near Lake
      Superior.

PMID- 1996911
TI  - Inhalation exposure to 1,3-dichloropropene in the Dutch flower-bulb culture. Part
      II. Biological monitoring by measurement of urinary excretion of two mercapturic
      acid metabolites.
AB  - A biological monitoring study was carried out in the Dutch flower-bulb culture to
      determine the relationship between respiratory occupational exposure to Z- and E
      1,3-dichloropropene (Z- and E-DCP) and urinary excretion of two mercapturic acid
      metabolites, N-acetyl-S-(Z- and E-3-chloropropenyl-2)-L- cysteine (Z- and E-DCP
      MA). Urinary excretion of Z- and E-DCP-MA, either based on excretion rates or on
      creatinine excretion, followed first order elimination kinetics after exposure.
      Urinary half-lives of elimination were 5.0 +/- 1.2 hr for Z-DCP-MA and 4.7 +/-
      1.3 hr for E-DCP-MA and were not statistically significantly different.
      Calculated coefficients of variation indicated that the half-lives of elimination
      of Z- and E-DCP-MA were quite consistent inter- and intra-individually. Strong
      correlations (r greater than or equal to 0.93) were observed between respiratory
      8-hr time weighted average (TWA) exposure to Z- and E-DCP and complete cumulative
      urinary excretion of Z- and E-DCP-MA. Z-DCP yielded three times more mercapturic
      acid than E-DCP, probably due to differences in metabolism. Z- and E-DCP were
      excreted 45 and 14% as their respective mercapturic acid metabolites. A
      respiratory 8-hr TWA exposure to the Dutch occupational exposure limit of 5 mg.m
      3 DCP would result in a complete cumulative excretion of 14.4 mg (95% confidence
      interval: 11.7-17.0 mg) Z-DCP-MA and 3.2 mg (95% confidence interval: 2.3-4.1 mg)
      E-DCP-MA.

PMID- 1996912
TI  - Transport of organochlorine residues in the rat and human blood.
AB  - Organochlorine residues (OCR)2 are poorly soluble in water and are transported in
      the organism bound by the blood components. The distribution among blood
      fractions (cells/plasma, lipoproteins/rest of plasma proteins) were variable
      depending on the residue (HCB, p p'-DDE, HCH, Aroclor 1260, PCP) and on the
      species (rat, man). Differences were not found between in vivo (after oral single
      dosing) and in vitro (blood incubation) experiments. Results indicated a high
      affinity of organochlorine residues for lipoproteins; however, binding to blood
      carriers was very weak as demonstrated by the rapid release of residues by
      elution through a reverse phase column. The effects of residue binding to blood
      components on the distribution kinetics to tissues are discussed.

PMID- 1996913
TI  - Identification of metabolites of 2-chlorodibenzofuran in the rat.
AB  - The hepatic metabolism of 2-chlorodibenzofuran was investigated in the rat. When
      2-chloro[14C]dibenzofuran was intravenously administered to bile duct-cannulated
      rats, about 90% of radioactivity was excreted in bile and urine within 6 hr, the
      bile being the preferential route. Another group of rats received oral
      administration of cold 2-chlorodibenzofuran and bile fluid was collected by
      surgical bile duct cannulation for qualitative analysis. Three hydroxylated
      metabolites were isolated by high performance liquid chromatography from the bile
      fluid after hydrolytic digestion with sulfatase and beta-glucuronidase and were
      identified by mass and nuclear magnetic resonance spectrometries to be 2-chloro
      3,7-dihydroxydibenzofuran, 2-chloro-3-hydroxydibenzofuran and 2-chloro-7
      hydroxydibenzofuran, respectively. Analyses of the radioactive bile fluid by thin
      layer chromatography revealed that there was no detectable amounts of
      unmetabolized 2-chlorodibenzofuran in the bile fluid and the hydroxylated
      metabolites were present not as aglycons but as conjugated substances. The
      results suggest that 2-chlorodibenzofuran is rapidly metabolized in the rat, and
      the 3 and/or 7 positions play an important role in the metabolism of 2
      chlorodibenzofuran.

PMID- 1996914
TI  - Acute toxicity of pure pentachlorophenol and a technical formulation to three
      species of Daphnia.
AB  - The acute toxicity of a technical formulation of pentachlorophenol (PCP) and pure
      pentachlorophenol to three age classes of Daphnia magna, and adult D. pulex and
      D. galeata mendotae was determined by static toxicity tests. The influence of a
      number of factors on toxicity of PCP was also examined. The 48-hr LC50 estimates
      for adult daphnids of the three species exposed to pure PCP were 1.78, 4.59 and
      0.51 mg/L, respectively, while those for the technical formulation were 2.57,
      3.66 and 0.33 mg/L, respectively. There was little difference in toxicity between
      the technical and pure PCP; however, toxicity of both forms of PCP was influenced
      by duration of exposure, age (and/or size) and species of test organism and pH of
      the test solution. Pentachlorophenol caused a toxic response over a very narrow
      range of concentrations, with the greatest response occurring immediately between
      0 and 24 hr. Pure PCP was equally toxic to all age classes of D. magna but
      susceptibility to technical PCP decreased with maturation. D. g. mendotae was ten
      times more sensitive than D. pulex to PCP. Pure PCP was significantly more toxic
      to D. magna at pH 5.5 than 7.0 with mean 48-hr LC50 values of 0.082 and 1.78 mg
      PCP/L, respectively. At 12 degrees C, the toxicity of both forms of PCP to D. g.
      mendotae and D. pulex did not differ significantly from that at 20 degrees C;
      however, technical PCP was significantly more toxic to D. magna at 12 degrees C
      for an exposure duration of 48 hr.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1996915
TI  - The acute and chronic toxicity of ten chlorinated organic compounds to the
      American flagfish (Jordanella floridae).
AB  - The acute toxicity (96-hr median lethal concentrations (LC50s) of ten chlorinated
      isomers of benzene, phenol, ethane, and ethylene to the American flagfish
      (Jordanella floridae) were determined in both static and flow-through systems.
      Chronic toxicity to embryo-larval fish was also estimated from hatching success
      and post-hatch survival as well as fry growth rates and survival. Maximum
      acceptable toxicant concentrations (MATC) were estimated where possible. In
      general, for both acute and chronic toxicity tests, the order of increasing
      relative toxicity based on the water-borne exposure concentrations was:
      chloroethanes, chloroethylenes, chlorobenzenes, and chlorophenols. Within groups,
      more highly chlorinated isomers were usually more toxic. The presence of
      suspended or colloidal 1,2,4,5-tetrachlorobenzene was observed in acute toxicity
      testing and affected toxicity estimates.

PMID- 1996916
TI  - Lifetime and current prevalence of specific psychiatric disorders among Vietnam
      veterans and controls.
AB  - To determine if Vietnam theater veterans were more likely than controls to have a
      specific psychiatric disorder other than posttraumatic stress disorder, the rates
      of specific psychiatric disorders were estimated using the Diagnostic Interview
      Schedule for national samples of veterans who served in Vietnam, other veterans
      of the Vietnam era, and matched civilian controls. Overall, there were few
      differences in rates of disorder between theater and other veterans; there were
      somewhat more differences between theater veterans and civilians. There were
      striking differences, however, in rates for most disorders, both lifetime and
      current, between male theater veterans with high levels of exposure to war zone
      stress and other male veterans or civilians. Female veterans exposed to high
      levels of war zone stress also had higher rates than other female respondents for
      several disorders.

PMID- 1996917
TI  - Traumatic events and posttraumatic stress disorder in an urban population of
      young adults.
AB  - To ascertain the prevalence of posttraumatic stress disorder (PTSD) and risk
      factors associated with it, we studied a random sample of 1007 young adults from
      a large health maintenance organization in the Detroit, Mich, area. The lifetime
      prevalence of exposure to traumatic events was 39.1%. The rate of PTSD in those
      who were exposed was 23.6%, yielding a lifetime prevalence in the sample of 9.2%.
      Persons with PTSD were at increased risk for other psychiatric disorders; PTSD
      had stronger associations with anxiety and affective disorders than with
      substance abuse or dependence. Risk factors for exposure to traumatic events
      included low education, male sex, early conduct problems, extraversion, and
      family history of psychiatric disorder or substance problems. Risk factors for
      PTSD following exposure included early separation from parents, neuroticism,
      preexisting anxiety or depression, and family history of anxiety. Life-style
      differences associated with differential exposure to situations that have a high
      risk for traumatic events and personal predispositions to the PTSD effects of
      traumatic events might be responsible for a substantial part of PTSD in this
      population.

PMID- 1996918
TI  - Depression and anxiety in relation to social status. A prospective epidemiologic
      study.
AB  - Longitudinal research in Stirling County, Atlantic Canada, indicated that during
      the 1950s and 1960s the prevalence of depression was significantly and
      persistently higher in the "low" socioeconomic status population than at other
      socioeconomic status levels. Anxiety was found to show a less clear picture.
      Incidence of depression after the study started was also higher among those who
      were initially in the low socioeconomic status group, supporting the view that
      the stress of poverty may be causally related to depression. There was also a
      trend for prior depression to be associated with subsequent downward social
      mobility, supporting the view that the concentration of depressed people at the
      lower end of the social hierarchy may result from handicapping aspects of the
      illness. Neither of these trends was statistically significant. More striking was
      evidence that, irrespective of socioeconomic status, depression carried a
      substantial risk for poor clinical course and outcome. Both depression and
      poverty tended to be chronic, and, accordingly, their association at the end of
      the study was influenced by their association at its beginning. The stability of
      the relationship between poverty and depression warrants the attention of
      caregivers and policymakers and raises new questions about strategies for the
      study of causal sequences.

PMID- 1996919
TI  - Does somatization disorder occur in men? Clinical characteristics of women and
      men with multiple unexplained somatic symptoms.
AB  - Somatization disorder is thought to be rare or nonexistent in men. We examined
      this hypothesis by assessing gender differences in DSM-III-R diagnostic status,
      demographic and clinical characteristics, functional limitations, self-reported
      health status, and psychiatric comorbidity in 30 men and 117 women who were
      referred for multiple unexplained somatic complaints. Twelve men and 68 women met
      DSM-III-R criteria for somatization disorder. Among those meeting criteria, there
      were few differences on any of the dimensions that were assessed. Different
      referral sources for women and men suggested differences in physicians'
      perceptions of somatic symptoms in men and women. We concluded that somatization
      disorder exists in men, and that women and men with somatization disorder show
      similar clinical characteristics.

PMID- 1996920
TI  - Evidence for geographical variations in the prevalence of schizophrenia in rural
      Ireland.
AB  - Geographical variations in the rate of occurrence of schizophrenia have been the
      subject of much speculation and controversy, but it has proved extremely
      difficult to establish the existence of the phenomenon within a given study area.
      Using current inpatient and outpatient records and information from key
      informants active in the community, this study sought to identify all cases of
      schizophrenia in 36 District Electoral Divisions, constituting a clinical
      catchment area of 25,178 persons in a rural Irish county. Though the overall
      prevalence rate (3.3 per 1000) was unremarkable, this obscured a substantial and
      significant variation in prevalence rates (from 0.0 to 14.3 per 1000) between
      District Electoral Divisions. Prevalence rates in five District Electoral
      Divisions made particular contributions to the overall deviation from a
      statistical model for random occurrences in space. The results indicate spatial
      inhomogeneity in the prevalence of schizophrenia in rural Ireland and imply
      geographical variation in environmental or genetic factor(s) of etiologic
      relevance.

PMID- 1996921
TI  - The cholinergic rapid eye movement induction test with arecoline in depression.
AB  - The cholinergic rapid eye movement (REM) induction test using arecoline
      hydrobromide, a cholinergic muscarinic receptor agonist, was studied in patients
      with affective disorder and in normal controls to determine whether or not
      depression is associated with enhanced induction of REM sleep by muscarinic
      agonists. Arecoline induced REM sleep in a dose-dependent fashion in both
      patients and controls compared with placebo infusions. Compared with normal
      controls, patients entered REM sleep significantly more rapidly following
      intravenous administration of 1.0 mg of arecoline hydrobromide than they did
      following administration of 0.5 mg of arecoline hydrobromide or placebo. These
      results, as well as those of previous studies, support the hypothesis that
      patients with affective disorder show a functional supersensitive induction of
      REM sleep in response to muscarinic receptor agonists and may be consistent with
      the hypothesis that functional muscarinic receptor "up regulation" is associated
      with depression.

PMID- 1996922
TI  - Reduced REM latency in depression: mechanical considerations.

PMID- 1996923
TI  - Distinguishing between content and form of speech.

PMID- 1996924
TI  - Impaired Wisconsin Card Sort performance in schizophrenia may reflect
      motivational deficits.

PMID- 1996925
TI  - The influence of transmeridian flight on human circulating lymphocytes.
AB  - We studied the influence of transmeridian flight on the number of circulating
      lymphocytes, which have a circadian rhythm with low values in the daytime. The
      number of T lymphocytes was found to be higher than the baseline value, yet its
      rhythmicity was maintained after eastward flight with an 8-h time difference. The
      number of OKB2+ as well as Leu11+ cells were suppressed after the flight. The
      change in the number of T lymphocytes occurred due to the increased number of
      OKT4+ lymphocytes. There was no correlation between the number of OKT4+
      lymphocytes and the plasma cortisol level, though plasma cortisol is a major
      factor in regulating the number of lymphocytes. These data showed that the number
      of helper/inducer T lymphocytes, B cells, and natural killer cells were affected
      by the physical conditions experienced after the flight. The changes in T
      lymphocytes were independent of those of plasma cortisol levels.

PMID- 1996926
TI  - Repeatability and protocol comparability of presyncopal symptom limited lower
      body negative pressure exposures.
AB  - Data on repeatability and comparability of different presyncopal symptom-limited
      lower body negative pressure (PSL-LBNP) exposure protocols, while scarce, are
      critical to the interpretation of studies using PSL-LBNP methods. To investigate
      if PSL-LBNP tolerance, heart rate, and blood pressure were repeatable, 11
      subjects were exposed to 4 PSL-LBNP tests; each test occurring at the same time
      of day, separated by at least 72 h, and using the same protocol. No significant
      differences were found in either the heart rate or blood pressure responses to
      the PSL-LBNP or the tolerance indices (cumulative stress index; maximum negative
      pressure tolerated; and duration of negative pressure exposure). To study the
      comparability of different PSL-LBNP protocols, nine subjects were exposed
      randomly to five PSL-LBNP tests using protocols that varied in stage duration but
      not pressure profile. The protocols had 1-, 3-, 5-, 7-, or 9-min stage durations.
      These PSL-LBNP exposures were conducted at the same time of day and separated by
      at least 72 h. While no differences were noted in either the response pattern or
      magnitude of heart rate or blood pressure to the differing protocols, the
      cumulative stress index and the duration of negative pressure exposure varied
      proportionally with the length of the stage durations. With the exception of the
      1-min protocol, the maximum negative pressure tolerated did not vary regardless
      of the protocol used.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1996927
TI  - Bone histomorphometric comparison of rat tibial metaphysis after 7-day tail
      suspension vs. 7-day spaceflight.
AB  - Using histomorphometric analysis, we compared the effects of 7 d spaceflight
      (Biocosmos 1667) and 7 d tail-suspension in tibiae of 12-13 weeks old male Wistar
      rats. The skeletal alterations induced by both true and simulated weightlessness
      in the proximal tibial metaphysis consisted of an inhibition of longitudinal
      growth as indicated by the reduction of the primary spongiosa thickness. In both
      primary and secondary spongiosae, the loss of trabecular bone was more extensive
      in flight rats than in suspended rats. Impairment in cancellous and endocortical
      osteoid surfaces occurred in microgravity and 1-G conditions but with greater
      magnitude in the spongy space in flight rats. In suspended rats, the cancellous
      mineralization rate was decreased, suggesting an alteration of the formation
      activity. Bone resorption remained unchanged in flight rats whereas a twofold
      increase occurred in simulated conditions. These data support the hypothesis that
      mechanisms of bone loss in space are not entirely identical to those of tail
      suspension model on Earth. New experiments allowing comparison between actual
      spaceflight and spaceflight simulations must be developed in order to explore
      common alterations and to understand differential mechanisms in the bone system.

PMID- 1996928
TI  - Circadian rhythmicity and sleep of aircrew during polar schedules.
AB  - Sleep and circadian rhythms of aircrew were studied during a 7-d polar schedule
      operated between London and Tokyo. Sleep, rectal temperature, and subjective
      alertness were recorded for 2 d before departure during the schedule, and for 10
      d after the return. Changes in sleep during the early part of the trip were due
      to sleep loss on the outward journey, but later these changes were related to the
      displacement of the circadian rhythm. The acrophases of the circadian rhythms of
      temperature were delayed by the outward journey, and amplitudes were reduced
      throughout the trip. During the return, aircrew reported high levels of tiredness
      which persisted until the second recovery night. Though the amounts of sleep
      obtained during the schedule were satisfactory for the aircrew as a group, some
      crewmembers experienced difficulties. Realignment of circadian rhythms was
      attained by an advance of the circadian phase in eight aircrew and by a delay in
      three, and resynchronization was achieved in all cases within 6 d.

PMID- 1996929
TI  - Epidermal growth factor-induced cell rounding is sensitive to simulated
      microgravity.
AB  - Epidermal growth factor (EGF) induces rapid rounding of A431 human epidermoid
      carcinoma cells. This process is dependent upon temperature and EGF
      concentration. To investigate the possible influence of gravity variations on EGF
      induced cell rounding of A431 cells, experiments were performed using a fast
      rotating clinostat and centrifuge, thereby simulating microgravity and higher
      gravity values, respectively. We demonstrated that simulated microgravity
      conditions enhance EGF-induced cell rounding significantly, whereas hypergravity
      values do not show significant effects on this process. These results suggest
      that simulated microgravity modulates growth factor-induced signal transduction.

PMID- 1996930
TI  - Inotropic and chronotropic effects of isoprenaline in rats exposed to 30 bar.
AB  - Inotropic and chronotropic responses to the beta-agonist, isoprenaline (ISO) were
      studied with a transducer located in the left ventricle and a catheter placed in
      the left femoral artery in anesthetized rats at 1 and 30 bar. The hemodynamic
      control values were equal in both series. During ISO infusion the chronotropy
      increased equally (34%) at 1 and 30 bar. The inotropy increased by 38% during ISO
      infusion at 1 bar (Series 1). Increased inotropy (44%), and unchanged chronotropy
      were found during compression to 30 bar (Series 2). The ISO evoked inotropic
      responses in absolute values were greater at 30 bar than at 1 bar. Nevertheless,
      an equal relative (%) increase in inotropy was found during ISO infusion at 30
      bar compared to 1 bar. The cardiac oxygen consumption was estimated to be 65%
      higher at 30 bar during ISO infusion compared to that at 1 bar.

PMID- 1996931
TI  - Experimental verification of effectiveness and harmlessness of the Qigong
      maneuver.
AB  - A series of experiments involving the Qigong (Q-G) maneuver were conducted after
      our preliminary studies in 1986. Eighteen active fighter pilots served as
      subjects. After mastery of the Q-G maneuver in 5-7 sessions of training, tests at
      +1 Gz further verified that the blood pressure raising effect of this maneuver
      has the characteristics of rapid rising, minimal fluctuation and being readily
      maintained. The 18 subjects then underwent centrifuge tests. The tolerance to
      Rapid Onset Rate (ROR) (1 G/s) G-load in a relaxed, unprotected condition was
      3.82 G on average; performing the Q-G maneuver, the tolerance rose to 6.64 G, an
      improvement of 2.82 G. One to two days later, 5 subjects with anti-G suits on and
      performing the Q-G maneuver tolerated 7.80 G on average (ROR 1 G/s), a gain of
      3.95 G. Another 9 subjects performing the Q-G maneuver endured high sustained G
      (HSG) (ROR 3 G/s) of 6.5 G for 74.4 s on average (max 96 s) and 3 subjects
      endured HSG of 7.0 G for 57 s on average (max 82 s). During centrifuge tests,
      recorded physiological values showed good tolerance of the subjects; the
      respiratory pattern was basically different from that of M-1 or L-1 maneuvers. In
      further testing the harmlessness of the Q-G maneuver, gas metabolism, ear lobe
      oximetry and 8-channel EEG were carried out on these subjects. All these indices
      plus close monitoring during centrifuge tests proved that the Q-G maneuver does
      not lead to hypoxia or hyperventilation. It has been shown that the Q-G maneuver
      is an innovative G-protective maneuver that is remarkably effective,
      theoretically interesting, reliable, and practical. Its mechanism warrants
      investigation.

PMID- 1996932
TI  - Effects of pre-exposures to a rotating optokinetic drum on adaptation to motion
      sickness.
AB  - The purpose of this study was to investigate the effects of two different pre
      exposure procedures on adaptation to motion sickness in a rotating circular
      vection drum. The 45 subjects were randomly divided into three groups. The
      control group only had a standard 16-min exposure to the drum rotating at 60
      degrees/s with no pre-exposure. The incremental exposure group had two separated
      4-min pre-exposure periods at 15 degrees/s and 30 degrees/s in the rotating drum
      immediately prior to the standard 16-min exposure period in the drum rotating at
      60 degrees/s. The abrupt-exposure group had the same pre-exposure procedure
      except the pre-exposure drum rotation speed was 60 degrees/s and was followed by
      the same standard exposure periods. Subjective motion sickness reports and a
      measure of gastric myoelectric activity (electrogastrogram, EGG) were obtained
      during the standard 16-min drum rotation period in all three groups. The results
      showed that subjects in the incremental exposure group reported significantly
      fewer motion sickness symptoms during the standard 16-min rotation period than
      did the subjects in the abrupt exposure group and the control group. Subjects in
      the incremental exposure group also had less tachyarrhythmia, abnormal gastric
      myoelectric activity associated with nausea, during the 16-min rotation period
      than did the subjects in the control and abrupt exposure group. Incremental
      exposure to motion stimuli may be a useful method for training resistance to
      visually-induced motion sickness.

PMID- 1996933
TI  - Motion sickness in operational bomber crews.
AB  - Airsickness has long been identified as a flying training issue. The present
      study sought to assess its impact in an operational setting. During a monthly
      wing safety meeting, 88 B-1B and B-52H crewmembers completed the "B-1B
      Airsickness Research File" questionnaire. The questionnaire responses were
      analyzed using ANOVA, Chi-square median tests, and multiple regression analyses.
      The percent of flights in which airsickness was experienced was found to be a
      function of crew position but not of aircraft type or the interaction of crew
      position and aircraft type. The degree of in-flight incapacitation experienced,
      however, was significantly predicted by the combination of crew position,
      aircraft type, and the amount of experience flying in bombers. Pilots reported
      the least amount of incapacitation, as did crewmembers who flew the B-1B and
      crewmembers with less bomber experience. Airsickness was reported to be a
      frequent occurrence among non-pilots in both aircraft. Experienced crewmembers
      were more likely to report an impact on their duties.

PMID- 1996934
TI  - Decompression sickness presenting as a viral syndrome.
AB  - Decompression sickness (DCS) is a well-known hazard of exposure to significant
      variations in ambient pressure. The diagnosis and management of DCS is frequently
      a source of confusion. Although the majority of cases are manifested by joint or
      limb pains (Type I DCS), patients may present with a wide array of symptoms, such
      as neurologic deficits, headache, fatigue, nausea, and respiratory difficulty. A
      thorough knowledge of the differential diagnosis and a strong index of suspicion
      are crucial to the proper management of DCS. Presented herein are two cases of
      altitude-related DCS which were confused initially with a viral syndrome. A
      discussion of the symptoms of DCS is included.

PMID- 1996935
TI  - The new FAA national automated ECG network: some aviation medical examiner
      experiences.
AB  - The Federal Aviation Administration (FAA) has required, since August 1, 1987,
      that aviation medical examiners (AMEs) transmit by telephone all
      electrocardiograms (ECGs) necessary for airman "Class I" medical certification.
      This relatively new airman certification requirement is centralized at the Civil
      Aeromedical Institute (CAMI) in Oklahoma City. In calendar year 1989, the FAA
      received 69,000 electronically transmitted electrocardiograms. CAMI uses
      Marquette Electronics software to interpret the ECG signals that are received
      from multi-channel equipment. The single-channel transmitted ECGs are hand
      screened at present. The FAA "automated" screening program is unique among
      governmental airman medical certification programs throughout the world. This
      paper presents, for potential future users, the authors' experiences with the new
      airman automated electrocardiographic certification requirement, and covers
      positive and negative features involved in the implementation and operation of
      the program. We conclude that while the new FAA automated ECG screening program
      has satisfactorily replaced the former "physician-intensive" manual screening
      process, the new system increases the AME's equipment and operation costs. These
      are passed on to the airman who is seeking certification.

PMID- 1996936
TI  - Determining aircrew helmet size design requirements using statistical analysis of
      anthropometric data.
AB  - Traditionally, the number of aircrew helmet size rolls has been determined using
      head length and breadth for specified percentile ranges of a target population.
      Helmet mounted display technology will require taking the third dimension (pupil
      vertex height) into account. Using data from "An Anthropometric Survey of 2000
      Royal Air Force Aircrew, 1970/1971," the three head dimensions of length,
      breadth, and pupil-vertex height were plotted for each subject. A minimum number
      of helmet sizes was calculated to achieve a reasonable quality of fit. The 93.5%
      of subjects grouped around the population mean was the largest fraction which had
      a reasonable quality of fit while using nine sizes. Attempts to fit a larger
      percentage would require either a large increase in the number of sizes or a
      relaxing of fitting quality.

PMID- 1996937
TI  - The history of the United States Air Force Pilot-Physician Program.
AB  - Individuals trained as both military physicians and military pilots have existed
      in the armed forces of the world since 1911. This paper traces the history of
      pilot-physicians in the United States Air Force. The USAF pilot-physician program
      was founded by Harry G. Armstrong in 1947 and continues to the present time. This
      article was researched using largely unpublished references and personal
      interviews.

PMID- 1996938
TI  - Cases from the aerospace medicine residents' teaching file. Case #40.
      Asymptomatic hematuria.

PMID- 1996939
TI  - Toxoplasmosis.

PMID- 1996940
TI  - The interactions of courtship, feeding, and locomotion in the behavioral
      hierarchy of the snail Helix aspersa.
AB  - Starvation both increased the number of snails that exhibited feeding (i.e.,
      increased feeding proclivity) and decreased the latencies of response to a food
      stimulus (i.e., increased food arousal). Feeding inhibited locomotion, although
      starvation itself had no effect. Sexual arousal (the intensity of courtship)
      increased locomotion, but only in the absence of a mating partner. Sexual
      proclivity (the likelihood of a snail to court with conspecifics) had no effect
      on locomotion. In general, proclivity and arousal had different effects on
      behavior. Food deprivation did not alter the preference of sexually aroused
      snails for sexual stimuli over food stimuli Both starved and fed courting pairs
      responded to a food stimulus only during periods of low sexual arousal, although
      when not sexually aroused, starved snails usually increased the amount of time
      they spent in contact with a food stimulus. These results suggest that courtship
      can suppress feeding and that the expression of feeding behavior is dependent
      upon the occurrence of low levels of sexual arousal (time sharing).

PMID- 1996941
TI  - Effects of conspecifics on feeding in Aplysia fasciata.
AB  - The presence of other Aplysia in the environment increases the time spent
      feeding. This finding is consistent with the hypothesis that a common arousal
      mechanism modulates feeding and reproductive behaviors. The arousal level is
      presumably increased by pheromones released by additional animals.

PMID- 1996942
TI  - Reversal of retrieval impairment caused by retroactive interference on a two-way
      active avoidance task in rats.
AB  - Rats were exposed to an open field with flashing light (OFL; 60-W lamp, 30 Hz,
      for 7 min) 2 h after training and/or 2 h before testing in a two-way active
      avoidance task (30 trials, 0.5-mA footshock). Post-training OFL presentation
      caused retroactive interference, i.e., a retrieval impairment/amnesia for the
      avoidance task. Pretest OFL exposure reversed the post-training OFL-induced
      retrieval deficit. Diazepam (2.0 mg/kg), atropine (2.0 mg/kg), and methylatropine
      (0.1 mg/kg) administered before post-training OFL presentation blocked the OFL
      amnesic effect. However, these drugs did not counteract the pretest OFL-induced
      recovery of retrieval. Atropine and methylatropine administered 2 h before
      testing to rats receiving only post-training OFL presentation canceled the OFL
      interfering effect. These results suggest: (1) that the amnesic effect of post
      training OFL is due to failure of retrieval of the avoidance task, (2) that the
      reversal of this retrieval impairment by pretest OFL exposure may involve either
      priming or state-dependent mechanisms, and (3) that there are different
      modulatory mechanisms involved in post-training and pretest OFL effects.

PMID- 1996943
TI  - Effects of acute and chronic stress and of genotype on oxotremorine-induced
      locomotor depression of mice.
AB  - The locomotor behavior of unstressed and stressed mice of two inbred strains,
      DBA/2 and C57/BL6, was investigated. Animals were tested in a toggle-floor box
      apparatus, 30 min after saline or oxotremorine treatment (ip). A dose of
      oxotremorine that did not depress the activity of naive mice (0.01 mg/kg) was
      chosen. Stressed mice were injected 24 h after either a single 2-h stress session
      (acute stress) or the last of 14 daily stress sessions of tube restraining
      (chronic stress). Acute stress did not modify the depressant effect of
      oxotremorine on locomotor behavior in either strain. On the contrary, chronic
      stress induced a clear sensitization of DBA but not C57 mice to the depressant
      effect of oxotremorine. These findings show that chronic stress may result in
      modifications of the cholinergic function, and its behavioral correlates, and
      that these changes are modulated by the genetic makeup.

PMID- 1996944
TI  - Diazepam impairs place learning in the Morris water maze.
AB  - The effect of diazepam (0.3, 1.0, and 3.0 mg/kg) on the acquisition and retention
      of place learning was evaluated. The analysis of escape latencies indicates that
      1.0 and 3.0 mg/kg diazepam significantly impaired the retention of spatial
      information. When a free swim trial was carried out only control animals showed
      spatial bias to the target quadrant. The absence of spatial bias in the group
      that received 0.3 mg/kg suggests that the amnesic effect of diazepam can be seen
      at doses similar to or even lower than the anxiolytic ones, and that the
      GABA/benzodiazepine receptor complex is highly sensitive to the cognitive
      impairment induced by diazepam in spatial tasks.

PMID- 1996945
TI  - Cold-induced impairment of delayed matching in rats.
AB  - Exposure to moderate, nonhypothermic cold temperature has been reported to affect
      a variety of behavioral and neural functions. To elucidate the effects of mild
      cold stress on short-term (working) memory, Long-Evans rats were exposed to an
      ambient temperature of either 2 degrees or 23 degrees C while performing a
      delayed matching task. At the beginning of each trial, rats were required to
      respond on one of two levers cued by a light. Following a delay of 2, 8, or 16 s,
      a response on the lever previously cued produced food reinforcement. Relative to
      performance at 23 degrees C, exposure to 2 degrees C occasioned no change in
      matching accuracy at the 2-s delay, a modest decrement at the 8-s delay, and a
      larger decrement at the 16-s delay. The cold exposure did not decrease colonic
      temperature. In addition to accuracy decrements, matching response times were
      consistently shorter during cold exposures. Cold-induced impairments were absent
      during removal of the memory component from the task, indicating the observed
      cold effects on memory were not due to impaired attentional, sensory, or motor
      processes. These data suggest that mild cold stress may impair active maintenance
      of information in working memory but not processes related to reference memory.

PMID- 1996946
TI  - Female-female interactions and social stress in prairie voles.
AB  - Trios of prairie voles (Microtus ochrogaster) composed of either two estrous
      sibling or nonsibling females and one male were monitored via time-lapse
      videotaping over 72 hr. Social and sexual behaviors were analyzed as a function
      of trio type (sibling or nonsibling) and fate (survivor or nonsurvivor) across 12
      h time blocks. Within nonsibling trios, females that were able to maintain
      prolonged physical contact with the male within the first 3 days of trio
      formation later survived and successfully produced litters; females that did not
      maintain male contact later died of undetermined causes, presumably related to
      social stress. Frequencies of sexual behavior were similar in both trio types and
      both surviving and nonsurviving females received equivalent amounts of copulatory
      stimulation from the male. Sibling groups exhibited higher levels of female
      female side-by-side contact; nonsibling groups exhibited greater amounts of
      female-initiated anogenital sniffing, and female-initiated aggression. Female
      female social interactions may be determined by prior familiarity and/or
      relatedness and may play a dominant role in determining the social organization
      and mating system of this species.

PMID- 1996947
TI  - Association between chemosensory stimuli and cesarean delivery in rat fetuses:
      neonatal presentation of similar stimuli increases motor activity.
AB  - Recent studies conducted in this laboratory indicated that prenatal chemosensory
      stimulation followed by cesarean delivery strongly affected postnatal
      responsiveness to odors derived from the administered substances. The present
      experiments were performed in order to examine if an associative process was
      responsible for such effects. In Experiment 1 rat fetuses during Gestational Day
      21 were exposed to a tenuous alcohol solution or to a lemon-containing solution
      either 40 or 10 min prior to cesarean delivery. All subjects were subsequently
      tested in terms of changes in neonatal motor activity when confronted with the
      odor of alcohol or lemon. Rats experiencing prenatal cues 10 min prior to
      delivery exhibited higher and differential responsiveness to the smell of these
      cues when compared to those experiencing similar solutions 40 min prior to
      delivery. In Experiment 2 each fetus sequentially experienced both cues.
      Subsequent tests confirmed that the delay between prenatal sensory experience and
      birth induction was critical in terms of significantly affecting olfactory
      mediated motor responses. The results suggest that consequences related with
      cesarean delivery act as an unconditioned stimulus capable of being associated
      with orosensory cues present in the amniotic fluid.

PMID- 1996948
TI  - Comparison of the effects of scopolamine administered before and after
      acquisition in a test of visual recognition memory in monkeys.
AB  - The effect of scopolamine on visual recognition memory in rhesus monkeys was
      assessed with a delayed nonmatching-to-sample task employing trial-unique
      stimuli. During the acquisition phase, 40 sample stimuli were presented
      sequentially. During the test phase, these same stimuli were presented in the
      reverse order, each paired with a novel stimulus. The animal was rewarded for
      choosing the novel stimulus in each pair. Two versions of this design were used.
      In Task 1, scopolamine (10.0 or 17.8 micrograms/kg) was administered 20 min prior
      to acquisition, which was followed immediately by the test phase. In Task 2, the
      drug was administered immediately after acquisition, which was followed 20 min
      later by the test phase. Performance was impaired in a dose-related manner in
      Task 1, but not at all in Task 2, indicating that the effects of scopolamine on
      performance cannot be attributed to an impairment either in the retrieval of
      stored information or in the attentive or perceptual discriminative processes
      needed for such retrieval, or, by implication, for storage. In addition, the
      forgetting curves for scopolamine in Task 1 were parallel to those of the control
      sessions; i.e., the curves did not diverge with increasing delay intervals,
      indicating that scopolamine did not increase the rate of forgetting. Taken
      together, the results suggest that scopolamine interferes selectively with the
      initial storage of the information to be remembered.

PMID- 1996949
TI  - Effects of food and mates on time budget in Aplysia fasciata: integration of
      feeding, reproduction, and locomotion.
AB  - This study examines the time budgeted to different behaviors in Aplysia fasciata
      under three conditions: (1) animals have constant access to food and mates: (2)
      there is access to food, but not to mates; (3) neither food nor mates are
      present. The data suggest a number of rules underlying behavioral integration:
      (1) Feeding, reproductive behaviors, and activity seem to be natural categories
      for behavioral choice. Feeding and reproductive behaviors are controlled in
      tandem by a common arousal mechanism, while time left over after animals feed and
      reproduce is distributed in a fixed ratio between locomotion (crawling and
      swimming) and inactivity (immobility and movement in place). (2) Relative
      distribution between different forms of locomotion and inactivity is modified by
      changes in motivational state. More time is spent swimming than crawling when
      feeding and/or mating is prevented, while more time is spent moving in place than
      immobile when the arousal level is increased. (3) Feedback control of feeding and
      reproduction is asymmetric. Satiation of feeding inhibits the common arousal. In
      the absence of food, time spent on reproductive behaviors increases due to
      disinhibition of the common arousal. By contrast, positive feedback arising from
      sexual behavior excites the common arousal. When mating is prevented by removing
      potential mates, time spent feeding decreases. (4) Generally, animals choose
      between performing the three main categories of behavior. Although Aplysia
      simultaneously can feed and mate, or locomote and mate, they do so infrequently.
      By contrast, different types of reproductive behaviors (male mating, female
      mating, egg-laying) are commonly performed simultaneously.

PMID- 1996950
TI  - Daily variation of multiple behaviors in Aplysia fasciata: integration of
      feeding, reproduction, and locomotion.
AB  - Daily variations in feeding, reproductive behaviors, and activity level were
      examined under three conditions: (1) animals had access to food and mates; (2)
      there was access only to food; (3) neither food nor mates were present. Behaviors
      differed in amplitude of variations from their daily mean value. Egg-laying had
      the strongest tendency to be clustered. Amplitude of variations in courtship and
      swimming was larger than those of immobility, crawling, and feeding, while moving
      in place was the least clustered behavior. Changes in state affected the tendency
      to be clustered. When food and mates were present, amplitude of variations became
      progressively larger for immobility, moving in place, crawling, and swimming.
      Behaviors differed in the degree to which variations were patterned as a 1/day
      oscillation. Relatively little of the variability in crawling, moving in place,
      courtship, and egg-laying was due to a 1/day oscillation under any condition. By
      contrast, a large proportion of the variability of immobility, swimming, mating,
      and eating was modulated by a 1/day oscillation in at least one condition. The
      contribution of a 1/day oscillation to variability differed in the conditions
      examined. For immobility and swimming, when food and mates were present, the
      1/day component of variability became smaller. By contrast, presence of mates led
      to an increase in the 1/day component of variability modulating feeding. Daily
      peaks of swimming and feeding were in phase with one another, and out of phase
      with mating and feeding. The ratio of locomotion to inactivity is constant,
      independent of change in external conditions. However, this ratio varied
      throughout the day. When food and mates were absent, variations of immobility and
      swimming were strongly related to variations in the inactivity ratio. When food
      and mates were added, this tendency decreased. The data suggest that daily
      variations in occurrence of behaviors can be accounted for by interactions
      between oscillators affecting Aplysia behavior and motivational variables. A
      1/day oscillator has strong effects on mating, swimming, and immobility. The
      effect of the oscillator is modified by changes in motivational state.

PMID- 1996951
TI  - Ragged N-termini and other variants of class A beta-lactamases analysed by
      chromatofocusing.
AB  - Four beta-lactamases excreted by Gram-positive bacteria exhibited
      microheterogeneity when analysed by chromatofocusing or ion-exchange
      chromatography. Ragged N-termini were in part responsible for the charge
      variants, but deamidation of an asparagine residue was also involved, at least
      for the Bacillus licheniformis enzyme. The activity of a contaminating proteinase
      could also be demonstrated in the case of Actinomadura R39 beta-lactamase. With
      that enzyme, proteolysis resulted in partial inactivation, but the inactivated
      fragments were easily separated from the active forms. With these, as with the
      other enzymes, the kinetic parameters of the major variants were identical with
      those of the mixture within the limits of experimental error, so that the
      catalytic properties of these enzymes can be determined with the 'heterogeneous'
      preparations.

PMID- 1996952
TI  - Fibroblast adhesion to recombinant tropoelastin expressed as a protein A-fusion
      protein.
AB  - A bovine tropoelastin cDNA encoding exons 15-36 that includes the elastin
      receptor binding site was expressed in Escherichia coli as a fusion protein with
      Protein A from Staphylococcus aureus. After isolation of the fusion protein by
      affinity chromatography on Ig-Sepharose, the tropoelastin domain was separated
      from plasmid-pR1T2T-encoded Protein A (Protein A') by CNBr cleavage. Cell
      adhesion assays demonstrated specific adhesion to the recombinant tropoelastin.
      Furthermore, the data indicate that interactions involving the bovine elastin
      receptor mediate nuchalligament fibroblast adhesion to the recombinant protein.
      In agreement with earlier studies of fibroblast chemotaxis to bovine
      tropoelastin, nuchal-ligament fibroblast adhesion demonstrated developmental
      regulation of the elastin receptor.

PMID- 1996953
TI  - Regulation of transformation-sensitive secreted phosphoprotein (SPPI/osteopontin)
      expression by transforming growth factor-beta. Comparisons with expression of
      SPARC (secreted acidic cysteine-rich protein).
AB  - Secreted phosphoprotein I (SPPI; osteopontin), a highly phosphorylated form of
      which has been associated with cell transformation, is one of the major
      phosphorylated proteins in bone. Populations of rat bone cells derived from fetal
      calvariae, neonatal parietal bone and a rat osteosarcoma cell line (ROS 17/2.8)
      produce several forms of the protein, the major forms having apparent molecular
      masses of 55 and 44 kDa by SDS/PAGE on 15% (w/v) cross-linked gels and of 60 and
      56 kDa on 10% gels. Northern blot analysis of SPPI mRNA using total cellular RNA
      revealed a single 1.5 kb mRNA species, indicating that the nascent protein chains
      of these phosphoproteins are identical. On treatment of the cells with
      transforming growth factor-beta (TGF-beta; 1 ng/ml), the levels of SPPI mRNA and
      the synthesis of the 55 kDa phosphoprotein, but not of the 44 kDa phosphoprotein,
      were increased by 1.8-4.5-fold in the normal osteoblastic cells, the stimulation
      first being evident at 3 h and reaching a maximum at 12 h. In the transformed ROS
      17/2.8 cells, TGF-beta did not alter significantly the SPPI mRNA level or the
      synthesis of either the 55 kDa or the 44 kDa SPPI over the 24 h period studied.
      By comparison, neither the steady-state levels of SPARC (secreted protein,
      acidic, rich in cysteine) mRNA nor the synthesis of SPARC protein were affected
      significantly by the addition of TGF-beta to any of the osteoblastic bone cells.
      The half-lives for SPPI and SPARC mRNAs in the osteoblastic calvarial cells were
      calculated to be 18 h and greater than 50 h respectively, in both the presence
      and the absence of TGF-beta. Since the stability of the mRNA was unchanged by TGF
      beta and the increased expression of SPPI mRNA could be blocked by cycloheximide,
      TGF-beta appears to increase transcription of the SppI gene indirectly by
      stimulating the synthesis of a protein that promotes transcription. These results
      demonstrate that several forms of SPPI are synthesized constitutively by bone
      cells, and that there are clear differences in the regulation of SppI gene
      expression by TGF-beta in normal bone cells compared with the tumorigenic ROS
      17/2.8 cells. The differential responses of normal osteoblastic cells to TGF-beta
      in the expression of SPPI and the selective stimulation of specific forms of the
      SPPI protein may be important in bone repair and remodelling.

PMID- 1996954
TI  - 'Slow-binding' sixth-ligand inhibitors of cytochrome P-450 aromatase. Studies
      with 19-thiomethyl- and 19-azido-androstenedione.
AB  - The progress curves for the inhibition of aromatase by 19
      thiomethylandrostenedione and 19-azidoandrostenedione were found to be non-linear
      where the extent of inhibition increased with time. Further experiments enabled
      these compounds to be classified as 'slow-binding' inhibitors of aromatase. The
      phenomenon was attributed to the formation of an initial E.I complex that
      rearranged to another species (E.I*) in which the interaction between the enzyme
      and inhibitor had been maximized, giving rise to tighter binding. When 19
      thiomethylandrostenedione was used as the inhibitor the t0.5 (half-time) for the
      dissociation of E.I* was calculated to be 12.6 min with Ki and Ki* values of 2.4
      and 1.4 nM respectively. In the case of 19-azidoandrostenedione, the two separate
      dissociation constants were not determined, and a single Ki value of 5 nM was
      obtained. The conclusions drawn from kinetic studies were confirmed by absorption
      spectrometry, when time-dependent formation of complexes between aromatase and
      either 19-thiomethylandrostenedione or 19-azidoandrostenedione were observed by
      the formation of 'Type II' spectra. The two complexes respectively had maxima at
      429 and 418 nm. The spectral data suggested that the two inhibitors interact with
      the haem iron of aromatase, forming hexaco-ordinated species for which structural
      models are presented.

PMID- 1996955
TI  - Distribution of iduronate 2-sulphate residues in heparan sulphate. Evidence for
      an ordered polymeric structure.
AB  - The structure of human skin fibroblast heparan sulphate has been examined by
      depolymerization with heparinase, which specifically cleaves highly sulphated
      disaccharides of structure GlcNSO3 (+/-6S)-alpha 1,4IdoA(2S) [N-sulphated
      glucosamine (6-sulphate)-alpha 1,4-iduronic acid 2-sulphate]. Heparan sulphate
      contained only a small proportion (approximately 10%) of linkages susceptible to
      this enzyme. The major products of depolymerization with heparinase were large
      oligosaccharides with an average molecular mass of 10 kDa (dp approximately 40,
      where dp is degree of polymerization; for disaccharides, dp = 2 etc.) as assessed
      by gel filtration on Sepharose CL-6B, compared with a molecular mass of 45 kDa
      (dp approximately 200) for the intact chains. The large heparinase-resistant
      oligosaccharides were highly susceptible to depolymerization with the enzyme
      heparitinase, which cleaves heparan sulphate in areas of low sulphation, where N
      acetylated disaccharides [GlcNAc-alpha 1,4GlcA (N-acetylglucosaminyl-alpha 1,4
      glucuronic acid)] are the predominant structural unit. Further analysis of the
      location of the heparinase cleavage sites indicated that they were predominantly
      found in a central position in GlcNSO3-alpha 1,4IdoA repeat sequences of average
      length four to seven disaccharides (dp 8-14). These results indicate that
      heparinase cleaves heparan sulphate in approximately four or five N-sulphated
      domains, each domain containing a cluster of two or three susceptible
      disaccharides; the domains are separated by long N-acetyl-rich sequences that are
      markedly deficient in sulphate groups. On the basis of these findings a model is
      proposed which depicts heparan sulphate as an ordered polymeric structure
      composed of an alternate arrangement of sulphate-rich and sulphate-poor regions.
      The sulphate-rich regions are likely to be flexible areas of the chain because of
      their high content of the conformationally versatile IdoA and IdoA(2S) residues.
      The model has important implications for the biosynthesis and functions of
      heparan sulphate.

PMID- 1996956
TI  - Purification and characterization of thermostable glucose isomerase from
      Clostridium thermosulfurogenes and Thermoanaerobacter strain B6A.
AB  - Glucose isomerases produced by Thermoanaerobacter strain B6A and Clostridium
      thermosulfurogenes strain 4B were purified 10-11-fold to homogeneity and their
      physicochemical and catalytic properties were determined. Both purified enzymes
      displayed very similar properties (native Mr 200,000, tetrameric subunit
      composition, and apparent pH optima 7.0-7.5). The enzymes were stable at pH 5.5
      12.0, and maintained more than 90% activity after incubation at high temperature
      (85 degrees C) for 1 h in the presence of metal ions. The N-terminal amino acid
      sequences of both thermostable glucose isomerases were Met-Asn-Lys-Tyr-Phe-Glu
      Asn and were not similar to that of the thermolabile Bacillus subtilis enzyme.
      The glucose isomerase from C. thermosulfurogenes and Thermoanaerobacter displayed
      pI values of 4.9 and 4.8, and their kcat. and Km values for D-glucose at 65
      degrees C were 1040 and 1260 min-1 and 140 and 120 mM respectively. Both enzymes
      displayed higher kcat. and lower Km values for D-xylose than for D-glucose. The
      C. thermosulfurogenes enzyme required Co2+ or Mg2+ for thermal stability and
      glucose isomerase activity, and Mn2+ or these metals for xylose isomerase
      activity. Crystals of C. thermosulfurogenes glucose isomerase were formed at room
      temperature by the hanging-drop method using 16-18% poly(ethylene glycol) (PEG)
      4000 in 0.1 M-citrate buffer.

PMID- 1996957
TI  - Properties of human testis-specific lactate dehydrogenase expressed from
      Escherichia coli.
AB  - The cDNA encoding the C4 isoenzyme of lactate dehydrogenase (LDH-C4) was
      engineered for expression in Escherichia coli. The Ldh-c open reading frame was
      constructed as a cassette for production of the native protein. The modified Ldh
      c cDNA was subcloned into the prokaryotic expression vector pKK223-3. Transformed
      E. coli cells were grown to mid-exponential phase, and induced with isopropyl
      beta-D-thiogalactopyranoside for positive regulation of the tac promoter. Induced
      cells expressed the 35 kDa subunit, which spontaneously formed the enzymically
      active 140 kDa tetramer. Human LDH-C4 was purified over 200-fold from litre
      cultures of cells by AMP and oxamate affinity chromatography to a specific
      activity of 106 units/mg. The enzyme was inhibited by pyruvate concentrations
      above 0.3 mM, had a Km for pyruvate of 0.03 mM, a turnover number (nmol of NADH
      oxidized/mol of LDH-C4 per min at 25 degrees C) of 14,000 and was heat-stable.

PMID- 1996958
TI  - Solution behaviour of Chromobacter viscosum and Pseudomonas sp. lipases. No
      evidence of self-association.
AB  - 1. The size of two bacterial lipases was studied by SDS/PAGE, sedimentation
      velocity and sedimentation equilibrium to test for possible self-association
      behaviour. 2. Mr values of selected lipases were obtained from SDS/PAGE and
      sedimentation-velocity measurements, together with an absolute determination by
      sedimentation equilibrium 3. The Mr values obtained in a variety of aqueous
      solvents indicate that lipases do not self-associate in solution, suggesting the
      absence of surface hydrophobic patches.

PMID- 1996959
TI  - Human cystatin C. role of the N-terminal segment in the inhibition of human
      cysteine proteinases and in its inactivation by leucocyte elastase.
AB  - Leucocyte elastase in catalytic amounts was observed to rapidly cleave the Val-10
      Gly-11 bond of the human cysteine-proteinase inhibitor cystatin C at neutral pH.
      The resulting modified inhibitor had size and amino acid composition consistent
      with a cystatin C molecule devoid of the N-terminal Ser-1-Val-10 decapeptide.
      Leucocyte-elastase-modified cystatin C had more than 240-fold lower affinity than
      native cystatin C for papain. Removal of the N-terminal decapeptide of human
      cystatin C also decreased inhibition of human cathepsins B and L by three orders
      of magnitude, but decreased inhibition of cathepsin H by only 5-fold. A
      tripeptidyldiazomethane analogue of of the N-terminal portion of cystatin C was a
      good inhibitor of cathepsins B and L but a poor inhibitor of cathepsin H. It
      therefore appears that amino acid side chains of the N-terminal segment of
      cystatin C bind in the substrate-binding pockets of cathepsins B and L but not in
      those of cathepsin H. It is argued that the N-terminal cystatin C interaction
      with cathepsin B is physiologically important and hence that leucocyte elastase
      could have a function as a regulator of extracellular cysteine-proteinase
      inhibitory activity at sites of inflammation.

PMID- 1996960
TI  - Early steps of isoprenoid biosynthesis in Escherichia coli.
AB  - The incorporation of 2H- and 13C-labelled precursors into ubiquinone-8 (Uq-8) by
      strains of Escherichia coli was measured in order to define the pathway for the
      early steps in the biosynthesis of isoprenoids in these eubacteria. Cells grown
      with DL-[methyl-2H6]valine were found to label both the alpha-oxoisovaleric
      ('alpha-ketoisovaleric') acid alpha-oxoisohexanoic ('alpha-ketoisocaproic') acid,
      but not the Uq-8. Since these acids are required for the biosynthesis of
      isoprenoids by the acetolactate pathway, the operation of this pathway in the
      biosynthesis of Uq-8 is excluded. Cells grown with [1,2-13C2]acetate and non
      labelled glucose readily incorporated 13C2 units into fatty acids, but failed to
      incorporate any label into the Uq-8. Cells grown with [U-13C6]glucose and non
      labelled acetate, however, were found to label both the fatty acids and the Uq-8.
      Oxidative cleavage with periodate/permanganate of the Uq-8 isolated from cells
      grown with U-13C6-labelled glucose produced laevulinic acid, which was shown to
      be derived from two C2 units and one C1 unit of the labelled glucose by mass
      spectral analysis of the 4,5-dihydro-6-methyl-2-phenylpyridazin-3(2H)-one
      derivative. The results of this work indicate that the C-2 and C-3 carbon unit of
      pyruvate, not acetyl-CoA, is the precursor to isopentenyl pyrophosphate (IPP) in
      these cells; however, the labelling pattern observed is consistent with the
      established acetoacetate pathway of isoprenoid biosynthesis. These data, coupled
      with the observed lack of inhibition of the growth of E. coli by mevinolin, a
      specific inhibitor of 3-hydroxy-3-methylglutaryl-CoA, can be best rationalized by
      the biosynthesis of IPP occurring in E. coli through a series of bound
      intermediates.

PMID- 1996961
TI  - Group B streptococci inactivate complement component C5a by enzymic cleavage at
      the C-terminus.
AB  - Incubation of recombinant human C5a (rC5a) with the 7360 strain of group B
      streptococci (GBS) destroyed the ability of rC5a to stimulate chemotaxis or
      adherence of purified human polymorphonuclear leucocytes (PMNs). Treatment of
      125I-labelled rC5a with GBS 7360 correspondingly decreased rC5a binding to human
      PMNs. This also resulted in an approx. 600 Da decrease in the molecular mass of
      rC5a as determined by SDS/PAGE. Incubation of rC5a with the GBS strain GW, which
      only minimally altered the ability of rC5a to activate human PMNs, did not affect
      rC5a binding to PMNs and did not alter the molecular mass of rC5a on SDS/PAGE.
      Plasma-desorption m.s. of rC5a inactivated by GBS 7360 showed that the GBS
      cleaved the rC5a between histidine-67 and lysine-68 near the C-terminus of rC5a.
      This mechanism of inactivation of C5a by proteolytic cleavage at the C-terminus
      of C5a is consistent with the known critical role of the C-terminus in C5a
      activation of human PMNs. This C5a-cleaving proteinase activity may contribute to
      the pathophysiology of GBS infections.

PMID- 1996962
TI  - Octanoate binding to the indole- and benzodiazepine-binding region of human serum
      albumin.
AB  - Binding of L-tryptophan, diazepam and octanoate to defatted human serum albumin
      was studied at pH 7.0 by equilibrium dialysis at low ligand/protein molar ratios.
      L-Tryptophan binding takes place at only one site of the protein with an
      association constant of 4.4 x 10(4) M-1. Under the present experimental
      conditions, binding of diazepam and octanoate could be accounted for by high
      affinity binding alone with primary association constants of 3.8 x 10(5) M-1 and
      1.6 x 10(6) M-1 respectively. During the simultaneous presence of L-tryptophan
      plus octanoate or diazepam plus octanoate, pronounced mutual reductions in
      binding were observed. Analysis of the data suggests that the reductions in
      binding represent competition for a common high-affinity binding site. Thus a
      region seems to exist that is capable of binding one molecule of these diverse
      ligands with a high affinity. The location of this region within the albumin
      molecule is discussed.

PMID- 1996963
TI  - Cell-shape regulation and matrix protein p52 content in phenotypic variants of
      ras-transformed rat kidney fibroblasts. Functional analysis and biochemical
      comparison of p52 with proteins implicated in cell-shape determination.
AB  - The 52 kDa transformation-sensitive protein p52 was previously identified as a
      major substrate-associated component of normal rat kidney (NRK) fibroblasts
      [Higgins & Ryan (1989) Biochem. J. 257, 173-182]. p52 selectively localized to
      cellular fractions enriched in substrate focal-contact sites and associated
      ventral undersurface elements. Rapid attachment/spreading of NRK cells on to
      prepared p52 matrices and inhibition of fibroblast spreading by antibodies to p52
      indicated that this protein participates in shape determination or cell-to
      substrate adhesion. NRK cells transformed with Kirsten murine sarcoma virus
      (KiMSV), with a temperature-sensitive mutant (ts-371 KiMSV) and maintained at the
      permissive temperature, or with the cloned EJrasval.12 oncogene, exhibited down
      regulated accumulation of p52 in the ventral undersurface region. Immunochemical,
      lectin-affinity and electrophoretic analyses indicated that p52 shares
      considerable sequence similarity with plasminogen-activator inhibitor type-1,
      which is consistent with its subcellular localization and likely morphoregulatory
      activity. The marked down-regulation of p52 expression seen in four different ras
      mediated transformation systems, its induction prior to butyrate-induced
      morphological reorganization in KiMSV-transformed cells, and the morphological
      consequences of exogenously added p52 or p52 antibodies on NRK fibroblasts
      suggest that this protein probably functions in cell-shape regulation. Abrogation
      of p52 matrix accumulation typically seen in ras transformants may contribute,
      therefore, to the aberrant cytoarchitecture characteristic of malignant
      fibroblasts.

PMID- 1996964
TI  - Cloning, sequencing and expression of cDNA for chick liver haem oxygenase.
      Comparison of avian and mammalian cDNAs and deduced proteins.
AB  - A cDNA from a chick liver library that encodes for haem oxygenase has been cloned
      and sequenced. Positive clones were identified with monospecific antibodies to
      the purified enzyme from chick liver and a cDNA of rat haem oxygenase-1. The
      length of the cDNA is 1258 bases. An open reading frame of 888 bases was
      identified by comparison of nucleotide and amino acid sequences with those
      previously identified for haem oxygenase of mammalian or avian origin. The
      protein corresponding to this fragment of DNA is composed of 296 amino acid
      residues and has a molecular mass of 33,509 Da, which is similar to that
      previously estimated for haem oxygenase purified from chick liver. Unequivocal
      identification of this clone as that complementary to haem oxygenase was provided
      by (a) comparison of amino acid compositions and partial sequences with those
      previously established for the purified enzyme, (b) comparison with nucleotide
      and amino acid sequences for haem oxygenase from rat and human sources and (c)
      expression in Escherichia coli with production of high levels of mRNA, protein
      and haem oxygenase activity after exposure of the transfected bacteria to
      isopropyl beta-D-thiogalactopyranoside (IPTG). Overall, the similarity of chick
      haem oxygenase to rat and human haem oxygenase (nucleotides 66% and amino acids
      62%) is moderately high. The region between proline-129 and alanine-157 is
      identical in all three enzymes, including histidine-135, which is proposed to
      play a key role in binding the substrate haem at the active centre of the enzyme.
      Northern blots also show that treatment of chicks with CdCl2, a potent inducer of
      haem oxygenase, results in increases in 1.65-1.70 kb mRNA, which hybridizes
      selectively to the full-length cDNA or to a synthetic 24-base oligonucleotide
      with sequence identical to that of a portion of the haem oxygenase cDNA. These
      results suggest that Cd-dependent induction of haem oxygenase is due to increased
      transcription of the gene or stabilization of its message.

PMID- 1996965
TI  - A new fluorescent probe for the equilibrative inhibitor-sensitive nucleoside
      transporter. 5'-S-(2-aminoethyl)-N6-(4-nitrobenzyl)-5'-thioadenosine (SAENTA)-chi
      2-fluorescein.
AB  - The N6-(4-nitrobenzyl) derivative of adenosine is a tight-binding inhibitor of
      the equilibrative inhibitor-sensitive nucleoside transporter of mammalian cells.
      A fluorescent ligand for this transporter has been synthesized by allowing an
      adenosine analogue. 5'-S-(2-aminoethyl)-N6-(4-nitrobenzyl)-5'-thioadenosine
      (SAENTA), to react with fluorescein isothiocyanate. The purified adduct had a
      SAENTA/fluorescein molar ratio of 0.92:1 calculated from its absorption spectrum.
      The intensity of fluorescent emission from the SAENTA-chi 2-fluorescein adduct
      was 30% that of fluorescein isothiocyanate (chi 2 is the number of atoms in the
      linkage between fluorescein and SAENTA). SAENTA-chi 2-fluorescein inhibited the
      influx of nucleosides into cultured leukaemic cells with an IC50 (total
      concentration of inhibitor producing 50% inhibition) of 40 nM. The adduct
      inhibited the binding of [3H]nitrobenzylthioinosine ([3H]NBMPR) with half-maximal
      inhibition at 50-100 nM. Mass Law analysis of the competitive-binding data
      suggested the presence of two classes of sites for [3H]NBMPR binding, only one of
      which was accessible to SAENTA-chi 2-fluorescein. Flow cytometry was used to
      analyse equilibrium binding of SAENTA-chi 2-fluorescein to leukaemic cells and a
      Kd of 6 nM was obtained. SAENTA-chi 2-fluorescein is a high-affinity ligand for
      the equilibrative inhibitor-sensitive nucleoside transporter which allows rapid
      assessment of transport capacity by flow cytometry.

PMID- 1996966
TI  - Cellular gels. Purifying and mapping long DNA molecules.
AB  - Long DNA molecules of greater than 10(5) bp (0.1 Mbp) are easily broken by
      pipetting. Therefore, chromosomal DNA is generally isolated after embedding cells
      in a protective coat of agarose. The embedded DNA can then be cut into long
      pieces and fractionated on gels using pulsed fields, but these pieces are again
      easily broken if the resolved DNA molecules are recovered from the gels. We now
      describe a novel gel matrix, a 'cellular' gel, that permits the recovery of
      resolved fragments from gels in a form that enables facile manipulation without
      shear. This facilitates purification and restriction mapping of fragments of 0.1
      1.0 Mbp. We illustrate the utility of the method by mapping chromosome III of
      baker's yeast, which has a length of approximately 0.36 Mbp. This method should
      facilitate purification and restriction mapping of yeast artificial chromosomes.

PMID- 1996967
TI  - Increased permeability to choline in simian erythrocytes after Plasmodium
      knowlesi infection.
AB  - The permeability of simian erythrocytes to choline was found to be considerably
      increased after infection by the malaria parasite, Plasmodium knowlesi. Choline
      entry occurs by a facilitated-diffusion system involving a carrier, which
      displays temperature-dependence, saturability with choline (Km = 8.5 +/- 0.7
      microM) and specificity. This carrier can also be inhibited by a thiol reagent, N
      ethylmaleimide, at an inactivation rate which is, in the absence of choline, the
      same as in normal erythrocytes. Inactivation by N-ethylmaleimide can be
      accelerated by external choline and prevented by decamethonium, which acts as an
      inhibitor of choline entry in infected cells (as with dodecyltrimethylammonium).
      Both ethanolamine and imidazole act as inhibitors or activators of choline entry
      in infected erythrocytes, depending on the relative concentrations of choline and
      of the competing compound (i.e. ethanolamine or imidazole). After infection, the
      maximum velocity reached 2.84 +/- 0.5 nmol/min per 10(10) infected cells, which
      is more than 10 times the Vmax. of normal erythrocytes. Impairing the
      biosynthesis of phosphatidylcholine de novo in Plasmodium-infected erythrocytes
      by various methods (glucose or ATP depletion, high ethanolamine concentrations)
      did not result in any alteration of choline transport (Km or Vmax.), indicating
      that the constant triggering and transformation of choline into
      phosphatidylcholine by the parasite is not directly responsible for the increase
      in the choline transport rate after infection. This high increase in choline
      transport activity is more likely related to modifications in choline carriers
      and/or in their environment after Plasmodium infection.

PMID- 1996968
TI  - Topography of succinate dehydrogenase in the mitochondrial inner membrane. A
      study using limited proteolysis and immunoblotting.
AB  - The arrangement of the large (70,000-Mr) and small (30,000-Mr) subunits of
      succinate dehydrogenase in the mitochondrial inner membrane was investigated by
      immunoblot analysis of bovine heart mitochondria (right-side-out, outer membrane
      disrupted) or submitochondrial particles (inside-out) that had been subjected to
      surface-specific proteolysis. Both subunits were resistant to proteinase
      treatment provided that the integrity of the inner membrane was preserved,
      suggesting that neither subunit is exposed at the cytoplasmic surface of the
      membrane. The bulk of the small subunit appears to protrude into the matrix
      compartment, since the 30,000-Mr polypeptide is degraded extensively during
      limited proteolysis of submitochondrial particles without the appearance of an
      immunologically reactive membrane-associated fragment: moreover, a soluble 27,000
      Mr peptide derived from this subunit is observed transiently on incubation with
      trypsin. Similar data obtained from the large subunit suggest that this
      polypeptide interacts with the matrix side of the inner membrane via two distinct
      domains; these are detected as stable membrane-associated fragments of 32,000 Mr
      and 27,000 Mr after treatment of submitochondrial particles with papain or
      proteinase K, although the 27,000-Mr fragment can be degraded further to low-Mr
      peptides with trypsin or alpha-chymotrypsin. A stable 32,000-34,000-Mr fragment
      is generated by a variety of specific and non-specific proteinases, indicating
      that it may be embedded largely within the lipid bilayer, or is inaccessible to
      proteolytic attack owing to its proximity to the surface of the intact membrane,
      possibly interacting with the hydrophobic membrane anchoring polypeptides of the
      succinate: ubiquinone reductase complex.

PMID- 1996969
TI  - Metalloendopeptidase QG. Isolation from Escherichia coli and characterization.
AB  - A new proteinase, which preferentially cleaves the Gln-Gly bond, was isolated
      from Escherichia coli. Because of this narrow specificity, the enzyme was called
      metalloendopeptidase QG. The proteinase is a monomer and consists of a single
      polypeptide chain of Mr 67,000, which is significantly smaller than the other
      known metalloendopeptidases of E. coli. It is found in the cytoplasm, but not in
      the periplasm. The enzyme cleaves the substrate benzyloxycarbonyl-Gln-Gly-Pro 2
      naphthylamide between the glutamine and glycine residues, as well as its extended
      homologues including a nonapeptide, but it does not hydrolyse either the oxidized
      A and B chains of insulin or azo-casein. The pH-dependence of substrate
      hydrolysis gives a bell-shaped curve with pK1 = 6.6 and pK2 = 8.8. The
      metallopeptidase is inhibited in Tris and imidazole buffers, the basic components
      of which are presumably liganded to the essential Zn2+ ion. 2-Aminobenzoyl-Gln
      Gly-Pro 2-naphthylamide, designed as a fluorescent substrate for the
      metallopeptidase, proved to be a strong inhibitor. Bestatin, an inhibitor of
      aminopeptidases in the micromolar concentration range, inhibits the
      metalloendopeptidase only in the millimolar concentration range. Captopril, the
      widely used inhibitor of angiotensin-converting enzyme, is a fairly good
      inhibitor of the metalloendopeptidase. The simplest inhibitor that can be used to
      protect recombinant proteins from degradation by the metalloendopeptidase may be
      EDTA, which is effective at low millimolar concentration.

PMID- 1996970
TI  - Low-Mr heparin is as potent as conventional heparin in releasing lipoprotein
      lipase, but is less effective in preventing hepatic clearance of the enzyme.
AB  - This study compares a low-Mr heparin preparation with conventional heparin with
      respect to its interaction with lipoprotein lipase (LPL) in vitro and its effects
      on the enzyme in vivo. Both heparin preparations were polydisperse in binding to
      LPL, but on average the low-Mr preparation showed lower affinity. Thus both
      conventional and low-Mr heparin bound quantitatively to immobilized LPL, and were
      eluted as broad peaks when a salt gradient was applied, but the peak for low-Mr
      heparin was shifted towards lower salt concentrations. To displace LPL from
      immobilized heparin a higher concentration of low-Mr than of conventional heparin
      was needed. Injection of the low-Mr heparin into intact rats resulted in lower
      plasma LPL activity than did injection of an equal mass of conventional heparin,
      but when the liver was excluded from the circulation both heparin preparations
      resulted in similar plasma LPL activities. In perfused rat hearts, low-Mr heparin
      had at least the same effect on the release of LPL activity as did conventional
      heparin. In perfused livers, on the other hand, low-Mr heparin was less effective
      than conventional heparin in preventing the rapid uptake of exogenous labelled
      LPL. Hence the apparently lower average affinity of low-Mr heparin for LPL does
      not result in a demonstrably lower potency to release the enzyme from endothelial
      binding sites in peripheral tissues, but does result in a substantially decreased
      effect on the hepatic clearance of the enzyme.

PMID- 1996971
TI  - Dynamically acetylated histones of chicken erythrocytes are selectively
      methylated.
AB  - The relationship between histone acetylation and methylation in chicken immature
      erythrocytes was investigated. Previous studies have shown that transcriptionally
      active/competent gene-enriched chromatin fragments are enriched in newly
      methylated histones H3 and H4. Moreover, newly methylated histone H4 is
      hyperacetylated. Here, we show that dynamically acetylated histone H4 is
      selectively engaged in ongoing methylation. While sodium butyrate (an inhibitor
      of histone deacetylase) does not inhibit ongoing histone methylation, it does
      affect the acetylation state of newly methylated histone H4 when chicken immature
      erythrocytes are incubated in its presence or absence. Only one rate of
      acetylation of labelled newly methylated unacetylated histone H4 with a t1/2 of 8
      min is observed. Previous studies have shown that the solubility of
      transcriptionally active/competent gene chromatin fragments in 0.15 M-NaCl is
      dependent upon the level of acetylated histone species, with induction of
      hyperacetylation increasing the solubility of this gene chromatin. Here, we show
      that the low salt solubility of chromatin fragments associated with newly
      methylated histones H3 and H4 is also dependent upon the level of acetylated
      histones. These results provide further support for the hypothesis that histones
      participating in ongoing methylation are associated with transcriptionally
      active/competent chromatin and suggest that the processes of histone H4
      methylation and dynamic acetylation are partially coupled in terminally
      differentiated erythrocytes.

PMID- 1996972
TI  - Two types of fatty acid-binding protein in human kidney. Isolation,
      characterization and localization.
AB  - Two types of fatty acid-binding protein (FABP) were isolated from human kidney by
      gel filtration and ion-exchange chromatography. Northern-blot analysis showed the
      presence of two FABP transcripts in total kidney RNA, hybridizing with cDNA of
      human liver and muscle FABP respectively. Characterisation based on molecular
      mass, isoelectric point, fluorescence with dansylaminoundecanoic acid and
      immunological cross-reactivity showed that one, type B, was fairly similar to
      human heart FABP. The other, type A, showed, like human liver FABP, a high
      fluorescence enhancement and a wavelength shift with dansylaminoundecanoic acid
      as well as the binding of a variety of ligands. Antibodies raised against FABP
      type A and against liver FABP markedly cross-reacted in e.l.i.s.a., in Western
      blotting and in indirect immunoperoxidase staining on kidney and liver sections.
      Differences in amino acid composition and isoelectric points, however, indicate
      that type A is a new kidney-specific FABP type. The FABP type A is more abundant
      in kidney than the B type and is predominantly localized in the cortex,
      especially in the cells of the proximal tubules. The FABP type B is mainly
      present in the cells of the distal tubules. In conclusion, this study shows the
      presence of two types of FABP in the kidney. One type seems to be related to
      heart FABP, while the other type resembles, but is not identical with, liver
      FABP. Both types have a characteristic cellular distribution along the nephron.

PMID- 1996973
TI  - Accumulation and metabolism of Ins(1,4,5)P3 and Ins(1,3,4,5)P4 in muscarinic
      receptor-stimulated SH-SY5Y neuroblastoma cells.
AB  - Stimulation of M3 muscarinic receptors expressed by SH-SY5Y cells induced a dose-
      and time-related increase in the mass of Ins(1,4,5)P3 (basal 38.3 +/- 5.8 pmol/mg
      of protein) and Ins(1,3,4,5)P4 (basal 6.1 +/- 1.2 pmol/mg of protein). Comparison
      of radioreceptor mass assays with [3H]inositol labelling showed higher-fold
      stimulations with the former protocol. The later accumulation of Ins(1,4,5)P3 and
      Ins(1,3,4,5)P4 mass was dependent upon extracellular Ca2+.

PMID- 1996974
TI  - A soluble 5'-nucleotidase in rat kidney. Stimulation by decavanadate.
AB  - A soluble 5'-nucleotidase was identified in rat kidney and partially purified.
      Compared with 5'-IMP, 5'-AMP was a poor substrate. The affinity for 5'-IMP was
      very low (S0.5 greater than 1 mM) in the absence of an activator, and it was much
      increased (S0.5 = 0.1 mM) by 2,3-bisphosphoglycerate (2,3-DPG). ATP and
      bisadenosyl tetraphosphate were further activators. The pH optimum was 6.3. Those
      properties suggest that the renal soluble 5'-nucleotidase is identical with the
      'high-Km' 5'-nucleotidase purified previously from liver, heart and erythrocytes.
      Decavanadate (100 nM) increased the rate of hydrolysis of 1 mM-5'-IMP 16-fold.
      The effect was specific for the decameric form of vanadate, since it was not
      reproduced by either decavanadate-free orthovanadate or pervanadate. Half-maximal
      activation was obtained at 1.4 nM-decavanadate. Decavanadate increased the
      affinity of the soluble 5'-nucleotidase for 5'-IMP. The effects of 2,3-DPG and of
      vanadate were not additive. Thus decavanadate probably influences the soluble 5'
      nucleotidase in the same way as 2,3-DPG, but with a much higher potency.

PMID- 1996975
TI  - Characterization of cholecystokinin receptors on guinea pig gastric chief cell
      membranes.
AB  - The binding of cholecystokinin (CCK) to its receptors on guinea pig gastric chief
      cell membranes were characterized by the use of 125I-CCK-octapeptide (CCK8). At
      30 degrees C optimal binding was obtained at acidic pH in the presence of Mg2+,
      while Na+ reduced the binding. In contrast to reports on pancreatic and brain CCK
      receptors, scatchard analysis of CCK binding to chief cell membranes revealed two
      classes of binding sites. Whereas, in the presence of a non-hydrolyzable GTP
      analog, GTP gamma S, only a low affinity site of CCK binding was observed. Chief
      cell receptors recognized CCK analogs, with an order of potency of: CCK8 greater
      than gastrin-I greater than CCK4. Although all CCK receptor antagonists tested
      (dibutyryl cyclic GMP, L-364718 and CR1409) inhibited labeled CCK binding to
      chief cell membranes, the relative potencies of these antagonists in terms of
      inhibiting labeled CCK binding were different from those observed in either
      pancreatic membranes or brain membranes. The results indicate, therefore, that on
      gastric chief cell membranes there exist specific CCK receptors, which are
      coupled to G protein. Furthermore, chief cell CCK receptors may be distinct from
      pancreatic or brain type CCK receptors.

PMID- 1996976
TI  - Induction of group II-like phospholipase A2 by lipopolysaccharide in the liver of
      BCG-primed rat.
AB  - The specific activity of phospholipase A2 (PLA2) in the liver homogenate was
      elevated 1.7-fold in bacillus Calmette-Guerin (BCG)-treated rats, 1.6-fold in
      lipopolysaccharide (LPS)-treated rats, and 2.4-fold in BCG-infected rats treated
      with LPS, compared with that of control rats. These increased activities were
      almost completely inhibited by the antibody directed against rat splenic group II
      PLA2 (PLA2M) but not by anti-pancreatic PLA2 antibody. The results of immunoblot
      analysis confirmed that the PLA2 immunochemically related to the group II enzyme
      was induced by treatment with BCG and/or LPS. The anti-PLA2M antibody-inhibitable
      PLA2 activity per a single cell was elevated not only in nonparenchymal cell
      fraction but also in hepatocyte fraction, as in the case of whole liver. On the
      contrary, the PLA2 concentration and its specific activity did not change by the
      same treatment both in spleen homogenate and in isolated spleen cell fractions
      although a 3-fold increase in spleen mass occurred by BCG treatment. These
      results suggested that a tissue-specific mechanism of the PLA2 induction by these
      inflammatory mediators may operate in liver.

PMID- 1996977
TI  - Purification of cytosolic 3,5,3'-triiodo-L-thyronine(T3)-binding protein(CTBP)
      which regulates nuclear T3 translocation.
AB  - The NADPH-dependent cytosolic 3,5,3'-triiodo-L-thyronine(T3)-binding
      protein(CTBP) was purified from rat kidney using Mono Q-Sepharose, Red sepharose
      and T3 affinity chromatography. CTBP which was partially purified by Red
      Sepharose column chromatography was adsorbed to T3 affinity column in the
      presence of 50 uM NADPH. The CTBP was eluted from the gel with the buffer which
      did not contain NADPH. One molecule of the purified CTBP(58 kDa) bound one
      molecule of T3 with 2.44 x 10(9) M-1 of affinity constant. The purified CTBP was
      activated not only by NADPH but also by NADP in the presence of dithiothreitol.
      The NADPH-activated form did not transfer T3 to nuclei, whereas NADP transformed
      the NADPH-activated CTBP to active form which was able to transfer T3 to nuclei.
      These results suggested that CTBP-dependent transport of T3 to nucleus is
      controlled by NADPH and NADP.

PMID- 1996978
TI  - Animal model of systemic carnitine deficiency: analysis in C3H-H-2 degrees strain
      of mouse associated with juvenile visceral steatosis.
AB  - We analyzed carnitine profiles in C3H-H-2 degrees strain of mouse associated with
      fatty liver, hyperammonemia and hypoglycemia (Koizumi et al., 1988). Carnitine
      levels in serum, liver and muscle of mouse with fatty liver were markedly
      decreased in comparison with those of control mouse (littermates without fatty
      liver). This is a useful animal model to analyze the role of carnitine in lipid,
      amino acid and carbohydrate metabolism.

PMID- 1996979
TI  - Vitamin E derivatives as new potent inhibitors of microsomal lipid peroxidation.
AB  - Several synthetic Vitamin E derivatives are strong inhibitors of lipid
      peroxidation induced in rat liver microsomes either chemically by ferrous ions
      and ascorbate or enzymatically by NADPH and carbon tetrachloride. The relative
      activities of these inhibitors are consistent with their intrinsic antioxidant
      properties, as peroxyl radicals scavengers. Among them, a 3,4-dihydro-6-hydroxy
      2H-1-naphtopyran with IC50 around 0.08 microM is one of the most potent yet known
      inhibitor of lipid peroxidation.

PMID- 1996980
TI  - Gastric cytoprotection by intracisternal interleukin-1 beta in the rat.
AB  - The effects of intracisternal (ic) injection of recombinant interleukin-1 beta
      (IL-1) on absolute ethanol-induced gastric necrotic lesions were studied in
      conscious rats. IL-1 given ic inhibited ethanol-induced gastric lesions. The
      cytoprotective effect was dose dependent (ED175 ng/rat), long lasting with a
      maximal action when given 1-3 h prior to ethanol, blocked by ic injection of a IL
      1 receptor antagonist protein (IRAP), and by intraperitoneal injection of
      indomethacin. IL-1, injected ic, was detected in the peripheral blood. However,
      IL-1 serum levels were lower after IL-1 injection ic than after ip at a dose
      giving equal gastric protection. These data show that ic IL-1 induces long
      lasting gastric protection mediated by interaction with IL-1 receptors and
      prostaglandin pathways at central and/or peripheral sites that remain to be
      localized.

PMID- 1996981
TI  - The mRNA levels of thyrotropin receptor, thyroglobulin and thyroid peroxidase in
      neoplastic human thyroid tissues.
AB  - Expression levels of thyrotropin receptor (TSH-R), thyroglobulin (Tg) and thyroid
      peroxidase (TPO) mRNA in normal and neoplastic human thyroid tissues (6 adenomas
      and 7 carcinomas) were investigated by Northern-blot and slot-blot analyses. We
      found that TSH-R mRNA levels were significantly lower in carcinoma tissues than
      in normal tissues. The levels of Tg mRNA were also significantly lowered in
      adenoma and carcinoma tissues as compared to normal tissues. In contrast, no
      significant difference was observed in the expression levels of TPO mRNA between
      these tissues. Furthermore, TSH-R mRNA levels were well-correlated with Tg mRNA
      levels in neoplastic tissues. These results suggest that mRNAs of TSH-R and Tg
      are expressed in relation to their degree of differentiation.

PMID- 1996982
TI  - The lectin wheat germ agglutinin induces rapid protein-tyrosine phosphorylation
      in human platelets.
AB  - In response to wheat germ agglutinin (WGA), platelet aggregation and stimulation
      of protein-tyrosine phosphorylation were observed in a dose dependent manner.
      These reactions were completely inhibited by coexistence of N-acetyl-D
      glucosamine with WGA. Upon stimulation by this agonist, protein-tyrosine
      phosphorylation of seven bands with molecular masses of 140-, 130-, 80-, 76-, 53
      , 38- and 35-kDa proteins was observed by immunoblot. These protein-tyrosine
      phosphorylations were divided into three groups by kinetics. Considering the
      previous report from our laboratory that thrombin and collagen induced tyrosine
      phosphorylation in 135-, 124- and 76-kDa proteins (Nakamura, S. and Yamamura, H.
      (1989) J. Biol. Chem. 264, 7089-7091.), there may be another signal transduction
      pathway in tyrosine phosphorylation of human platelets.

PMID- 1996983
TI  - Amino acids and peptides. XIV. Laminin related peptides and their inhibitory
      effect on experimental metastasis formation.
AB  - Inhibitory effects of synthetic laminin related peptides on experimental
      metastasis formation in mice were examined. Of the synthetic peptides, YIGSRG
      [amino-poly(ethylene glycol)] hybrid exhibited the most potent inhibitory effect
      on the metastasis of B16 melanoma BL6.

PMID- 1996984
TI  - Solution conformation of Forssman antigen probed by NOE and exchange
      interactions.
AB  - The conformation of Forssman glycolipid, GalNAc alpha 1-3GalNAc beta 1-3Gal alpha
      1-4Gal beta 1-4Glc beta 1-1ceramide, was analysed with the aid of the rotating
      frame NOE and Hartmann-Hahn spectroscopy. NOE contacts between C-, O-, and N
      linked protons were used for distance mapping. The glycosidic bonds that are
      common to globotriaosylceramide and globoside showed a similar flexibility as
      found for these compounds [Poppe et al., (1990) Eur. J. Biochem. 189, 313-325; J.
      Am. Chem. Soc. 112, 7762-7771]. In contrast, the conformational mobility of the
      terminal GalNAc alpha 1-3GalNAc beta linkage appears to be restrained. A new
      approach, based on 2D exchange spectroscopy, was proposed for revealing of
      spatial proximities between exchangeable protons in Me2SO solution.

PMID- 1996985
TI  - Structural and expression analyses of normal and mutant mRNA encoding glycine
      decarboxylase: three-base deletion in mRNA causes nonketotic hyperglycinemia.
AB  - Full-length cDNA clone encoding human glycine decarboxylase (P-protein) was
      isolated from the human placental lambda gt11 expression library using specific
      antibodies. This clone was 3,705 bp in length and encoded 1,020 amino acids. We
      studied the structure of the mutant P-protein mRNA expressed in the liver of a
      patient with nonketotic hyperglycinemia (NKH) deficient of P-protein. A three
      base deletion, which resulted in deletion of Phe756, was found. Cos7 cells in
      which normal P-protein cDNA was expressed presented an activity of 6.9 +/- 0.41
      nmole/milligram of protein/hour, which was almost equivalent to that of human
      liver. In contrast, Cos7 cells in which the mutant cDNA was expressed showed no
      activity, indicating that the three-base deletion could cause NKH.

PMID- 1996986
TI  - The precursor of mitochondrial aspartate aminotransferase is imported into
      mitochondria faster than the homologous cytosolic isoenzyme with the same
      presequence attached.
AB  - Mitochondrial and cytosolic aspartate aminotransferase (AspAT) are homologous
      proteins with identically folded polypeptide chains. The cDNAs of the two
      isoenzymes of chicken were used to express the following proteins in yeast: the
      precursor of mitochondrial AspAT, mature mitochondrial AspAT, and two chimeric
      proteins in one of which (pc) the presequence of the precursor was attached to
      the entire cytosolic isoenzyme and in the other one (pmc) the N-terminal segment
      (amino acid residues -22 to 23) of the precursor was linked to the slightly
      truncated cytosolic isoenzyme (residues 34 to 412). All presequence containing
      proteins were imported into the mitochondria and processed to the mature form
      whereas mature mitochondrial AspAT remained in the cytosol. The rate of import of
      the authentic precursor was four times faster than that of the chimeric proteins
      pc and pmc, t1/2 for importation at 29 degrees C being 3, 13 and 14 min,
      respectively. Apparently, the mature moiety of the precursor of mitochondrial
      AspAT promotes importation.

PMID- 1996987
TI  - Hepatic glucocorticoid receptor behaves differently when its hormone binding site
      is occupied by agonist (triamcinolone acetonide) or antagonist (RU486) steroid
      ligands.
AB  - We have examined the influence of sulfhydryl (SH)-group modifying agents on the
      interaction of the rat liver glucocorticoid receptor (GR) with its known agonist
      triamcinolone acetonide (TA) and the newly synthesized antagonist mifepristone
      (RU486). In the freshly prepared cytosol, [3H]TA or [3H]RU486 bound to
      macromolecule(s) which sediment as 8-9 moieties: the binding of either ligand can
      be competed with radioinert TA or RU486. The presence of 2-10 mM dithiothreitol
      (DTT), beta-mercaptoethanol (beta-MER), and monothioglycerol (MTG) caused a 2-3
      fold increase in the [3H]TA and [3H]RU486 binding to GR. Iodoacetamide (IA) and N
      ethylmaleimide (NEM) decreased the agonist binding significantly. In contrast,
      the [3H]RU486 binding to GR increased by 50 percent in the presence of IA. IA and
      NEM inhibited the binding of the heat-transformed [3H]TA-receptor complex to DNA
      cellulose by 70-90 percent whereas DNA binding of [3H]RU486-bound GR was
      inhibited only slightly. These results indicate that either a) the interaction of
      GR with the agonist or antagonist steroid ligands causes differential structural
      alterations, which are more readily detectable in the presence of SH-modifying
      agents or b) the agonist and the antagonist interact with distinct steroid
      binding sites.

PMID- 1996988
TI  - Reduction in the Ca2(+)-induced Ca2+ release from canine cardiac sarcoplasmic
      reticulum following endotoxin administration.
AB  - Effects of endotoxin administration on the Ca2(+)-induced Ca2+ release from
      canine cardiac sarcoplasmic reticulum (SR) were studied. Results show that the
      Ca2(+)-induced Ca2+ release from either passively or actively loaded SR vesicles
      was decreased by 28 to 46% (p less than 0.05) 4 h after endotoxin administration.
      Kinetic analysis reveals that the Vmax for Ca2+ was decreased significantly
      without changing the S0.5 and the Hill coefficient values. The binding of
      [3H]ryanodine to cardiac SR was reduced by 25.3% (p less than 0.01) following
      endotoxin administration. These data demonstrate that the Ca2(+)-induced Ca2+
      release via the ryanodine-sensitive Ca2+ channel in canine cardiac SR was reduced
      during endotoxin shock. A reduction in the SR Ca2(+)-induced Ca2+ release may
      have a pathophysiological significance in contributing to the development of
      myocardial depression during endotoxin shock.

PMID- 1996989
TI  - The stimulatory effect of PDGF on vascular smooth muscle cell migration is
      mediated by the induction of endogenous basic FGF.
AB  - The migration of arterial smooth muscle cells from the media to the intima is a
      crucial event for the development of the atherosclerotic lesion, and platelet
      derived growth factor (PDGF) is thought to play an important role in this
      process. Here we report that the spontaneous migration of bovine smooth muscle
      (BSM) cells is dependent on endogenously produced basic fibroblast growth factor
      (bFGF). PDGF stimulates the migration of BSM cells and its effect is abolished by
      affinity purified anti-bFGF antibody. PDGF induces bFGF mRNA in BSM cells. These
      results indicate that the effect of PDGF on the migration of BSM cells may be
      mediated by the induction of endogenous bFGF.

PMID- 1996990
TI  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin increases reliance on fats as a fuel source
      independently of diet: evidence that diminished carbohydrate supply contributes
      to dioxin lethality.
AB  - The environmental toxin, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes a
      wasting syndrome marked by hypophagia, loss of body fat, changes in intermediary
      metabolism and death. Use of conventional laboratory animals has not resolved
      whether or not TCDD affects intermediary metabolism independently of hypophagia.
      We used the chick embryo, which does not require an exogenous food supply for
      energy, to answer this question. Our results show that TCDD treatment increases
      dependence on fats as a fuel source independently of changes in food intake and
      therefore can affect intermediary metabolism independently of hypophagia. Results
      of experiments using aminocarnitine to inhibit fatty acid oxidation suggest that
      TCDD treatment impairs carbohydrate production rather than its utilization and
      that the former effect contributes to TCDD lethality.

PMID- 1996991
TI  - Cultured epithelial cells from patients with cystic fibrosis have an increased
      expression of the 14 kDa Ca2(+)-binding protein CFA.
AB  - The Cystic Fibrosis antigen (CFA) is a 14 kDa. Ca2(+)-binding protein known to be
      expressed in cells of myeloid origin during normal cell differentiation. CFA
      serum levels are elevated in Cystic Fibrosis (CF) patients and heterozygotes. We
      examined the expression of CFA in different cultured epithelial cells from
      controls and patients with CF. The steady state level of CFA was in general
      higher in epithelial cells from CF patients compared to control cells and was
      found to increase during cell aging. The latter difference could be attributed to
      an increased rate of CFA synthesis rather than to an impairment of CFA
      degradation or secretion, as shown by pulse chase experiments.

PMID- 1996992
TI  - Interleukin-4 is a potent mitogen for capillary endothelium.
AB  - Interleukin-4 (IL-4) is a mitogen for both microvascular (human adrenal
      capillary, HACE) and large vessel (human umbilical vein, HUVEC) endothelial
      cells. Comparison of growth promotion by IL-4 to that by the potent endothelial
      mitogen fibroblast growth factor (FGF) showed the activity of IL-4 on HACE cells
      to be strong (50% of that with FGF) but on HUVEC's weak (12% of that with FGF).
      Growth stimulation was characterised by both 3H-thymidine incorporation and by
      cell number, and was maximal at 1 nM IL-4. The presence of IL-4 receptors on HACE
      cells and HUVEC's was confirmed by specific binding of radioiodinated IL-4.
      Scatchard analysis confirmed a single high affinity binding receptor on both HACE
      cells (Kd = 80 pM, 358 receptors/cell) and HUVEC's (Kd = 88 pM, 2,580
      receptors/cell). Potent activity on capillary as opposed to large vessel
      endothelium places IL-4 in a unique position amongst endothelial mitogens.

PMID- 1996993
TI  - Introduction of single-stranded ADH genes into Drosophila results in tissue
      specific expression.
AB  - We injected single-stranded circular DNA containing a Drosophila Adh gene into
      ADH-negative embryos of Drosophila melanogaster and performed ADH histochemical
      staining on third instar larvae of the injected generation. Introduction of
      either the coding or non-coding strand resulted in correct tissue-specific
      expression of the Adh gene in larvae. Southern blotting revealed that the bulk of
      the injected DNA became double-stranded shortly after injection and was not
      integrated into the genome.

PMID- 1996995
TI  - The existence of unique B structures in polynucleotides with alternating purine
      pyrimidine sequences.
AB  - The infrared spectra of the sodium salts of calf-thymus DNA, poly(dA-dC).poly(dG
      dT), poly(dA-dT) and poly(dG-dC) were measured for the samples as highly
      hydrated, nonoriented gels. The bands from the sugar-phosphate vibrational modes
      show that poly(dG-dC) assumes a B-family structure which is different from the B
      structures of the other samples. Poly(dG-dC) most likely assumes a wrinkled B
      structure. The other samples retain a smooth B structure. An alternating purine
      pyrimidine sequence is not a sufficient condition for the formation of wrinkled B
      structure in a polynucleotide.

PMID- 1996994
TI  - Identification of the leucine-rich amelogenin peptide (LRAP) as the translation
      product of an alternatively spliced transcript.
AB  - The polymerase chain reaction was used to amplify bovine tooth amelogenin cDNA,
      resulting in several products which were separated by agarose gel
      electrophoresis. Sequence determination of one of the products revealed that it
      encoded an amino acid sequence identical to that of a small leucine-rich
      amelogenin polypeptide (LRAP) previously characterized by protein sequencing.
      Comparison of the nucleotide sequence of this cDNA with that determined for the
      cloned bovine amelogenine gene strongly suggested that the LRAP transcript
      resulted from alternative splicing of the primary transcript of this gene, thus
      explaining the origin of the puzzling LRAP sequence. Analysis of the structure of
      LRAP suggests that the polypeptide might exhibit interesting properties relative
      to hydroxy apatite crystal formation.

PMID- 1996996
TI  - Bilateral hydrophobic zipper as a hypothetical structure which binds acidic
      ribosomal protein family together on ribosomes in yeast Saccharomyces cerevisiae.
AB  - Acidic ribosomal protein family of yeast Saccharomyces cerevisiae consists of
      four species of 13-kDa proteins and one species of 38-kDa protein. These proteins
      are thought to form a complex on ribosomes functioning in the translational
      elongation reaction, but the structural basis how to associate with one another
      is not known. In this communication, we show for the first time the presence of a
      structure equivalent to the leucine zipper on a putative alpha-helix in the 38
      kDa acidic ribosomal protein, A0. Then, all the 13-kDa acidic ribosomal proteins
      are shown to have two periodic arrays of hydrophobic amino acid residues arranged
      on the opposite sides of a putative alpha-helix, which is referred to as the
      "bilateral hydrophobic zipper". Therefore, it is proposed that one of the 13-kDa
      acidic ribosomal proteins associates with 38-kDa protein A0 via the hydrophobic
      zipper and then the other 13-kDa proteins associate side by side via the
      bilateral hydrophobic zippers.

PMID- 1996997
TI  - Bioluminescent immunoassay using a monomeric Fab'-photoprotein aequorin
      conjugate.
AB  - The photoprotein aequorin emits light by an intermolecular reaction when mixed
      with Ca2+. To apply a bioluminescent immunoassay based on the light emission
      property of aequorin, we prepared aequorin-antibody Fab' conjugates by a chemical
      cross-linking technique. Recombinant apoaequorin was coupled with human tumor
      necrosis factor-alpha (TNF-alpha) antibodies (polyclonal Fab' or monoclonal Fab'
      fragments) using N-succinimidyl 4-(N-maleimidemethyl)cyclohexane-1-carboxylate.
      The luminescent activity of the Fab'-aequorin conjugate was about one-tenth that
      of aequorin. Using a monomeric conjugate, human TNF-alpha can be measured at an
      attomole level by a sandwich immunoassay technique.

PMID- 1996998
TI  - Translocation of the yeast dolichol-phosphate-mannose synthase into microsomal
      membranes.
AB  - Dolichol-phosphate-mannose synthase catalyzes the formation of Dolichol-phosphate
      mannose from Dolichol-phosphate and GDP-mannose. Analysis of the primary amino
      acid sequence of the yeast enzyme predicts a luminal orientation of the enzyme in
      the endoplasmic reticulum. We analysed the translocation of the Dolichol
      phosphate-mannose synthase into dog pancreatic microsomal membranes: resistance
      to proteolytic attack provides evidence of its luminal orientation and asks for a
      reevaluation of the topology of the reaction.

PMID- 1996999
TI  - Adamantane as a brain-directed drug carrier for poorly absorbed drug:
      antinociceptive effects of [D-Ala2]Leu-enkephalin derivatives conjugated with the
      1-adamantane moiety.

PMID- 1997000
TI  - Distamycin inhibits the binding of a nuclear factor to the -278/-256 upstream
      sequence of the human HLA-DR alpha gene.
AB  - In this study we analyse the effects of the anti-tumor compound distamycin on the
      binding of nuclear factor(s) to a synthetic oligonucleotide (GTATA/IFN-gamma)
      mimicking a putative regulatory region of the human HLA-DR alpha gene. This
      region contains the sequence (GTATA), that is required for nuclear protein
      binding and is likely to interact with distamycin. The present results, by
      showing that distamycin inhibits the interaction between nuclear factors and the
      GTATA/IFN-gamma oligonucleotide, suggest that distamycin might alter the binding
      of transacting factors to cis-elements containing AT/TA sequences. Alterations of
      nuclear protein binding to specific target sequences could be one of the
      molecular mechanism(s) by which distamycin exerts its antiproliferative activity
      on living cells.

PMID- 1997001
TI  - Inhibition of T cell mitogenesis by nitrofurans.
AB  - A group of nitrofurans (5-nitro-2-furaldehyde, nifuroxime, nitrofurazone,
      nitrofurantoin, 5-nitro-2-furoic acid and 2-nitrofuran) were evaluated for
      inhibition of mitogenesis (DNA synthesis) in human peripheral blood T cells. T
      cells, either triggered by phorbol myristate acetate (PMA) or in the presence of
      accessory cells, were activated with a specified mitogen [phytohemagglutin (PHA),
      concanavalin A (ConA), or anti-CD3] and the amount of tritiated thymidine
      incorporated into DNA was determined. The results obtained indicate that
      nitrofurans inhibit mitogenesis irrespective of activator. 5-Nitro-2-furaldehyde
      was much more inhibitory than the other compounds, while 2-nitrofuran was less
      inhibitory. When the aldehyde group (5-nitro-2-furaldehyde) was replaced by a
      carboxyl group (5-nitro-2-furoic acid), the inhibitory activity was also reduced
      greatly. These results show that while the nitro group alone confers inhibitory
      activity to the furan ring, the group at the 2 position is crucial. In general,
      the mitogenic response of purified T cells (lacking accessory cells) triggered by
      PMA (phorbol ester) was inhibited less than that of the T cell-accessory cell
      system. With the latter, 50% inhibition of T cell mitogenesis was achieved by
      nifuroxime, nitrofurazone, and nitrofurantoin at 45-51 and 34-39 microM with PHA
      and ConA respectively. When purified T cells were used, the values were 71-85 and
      55-60 microM respectively. For a given drug concentration, mitogenesis was more
      inhibited when induced by ConA or anti-CD3 than by PHA. The importance of using a
      single cell system (purified T cells) was emphasized by the interesting finding
      that only this system showed enhancement of mitogenesis, up to 35-40% at low drug
      levels. With the exception of the nitrofuraldehyde, the nitrofurans at strongly
      inhibitory levels were only moderately cytotoxic, exhibiting 62-85% cell survival
      after exposure to drug for 68 hr. Our results suggest that nitrofurans inhibit T
      cell mitogenesis by a relatively non-toxic mechanism; these results are
      comparable to those obtained for mammalian cells under aerobic conditions.

PMID- 1997002
TI  - Esterase activity in rat hepatocytes.
AB  - Hydrolysis of acetylsalicylate, benorylate, phenetsal, fluazifop butyl and
      paraoxon has been studied with freshly isolated rat hepatocytes maintained as a
      monolayer. Acetylsalicylate and paraoxon were the poorest substrates for
      hydrolysis whereas benorylate was hydrolysed one hundred times faster. Phenetsal
      and fluazifop butyl were both hydrolysed at one-tenth of the rate of benorylate.
      Inhibitor studies with paraoxon, BNPP and physostigmine indicated the involvement
      of different carboxylesterase isozymes. Studies with acetylsalicylate indicated
      that uptake of the substrate into the hepatocyte may influence the rate of
      formation of the hydrolysis product. Studies of hydrolysis in hepatocytes more
      closely reflect in vivo hepatic hydrolysis than subcellular fractions as
      cytosolic and microsomal esterases can act in parallel.

PMID- 1997003
TI  - Hydroxylation and formation of electrophilic metabolites of tienilic acid and its
      isomer by human liver microsomes. Catalysis by a cytochrome P450 IIC different
      from that responsible for mephenytoin hydroxylation.
AB  - Tienilic acid (TA) is metabolized by human liver microsomes in the presence of
      NADPH with the major formation of 5-hydroxytienilic acid (5-OHTA) which is
      derived from the hydroxylation of the thiophene ring of TA. Besides this
      hydroxylation, TA is oxidized into reactive metabolites which covalently bind to
      microsomal proteins. Oxidation of an isomer of tienilic acid (TAI), bearing the
      aroyl substituent on position 3 (instead of 2) of the thiophene ring, by human
      liver microsomes, gives a much higher level of covalent binding to proteins. Both
      covalent binding of TA and TAI metabolites are almost completely suppressed in
      the presence of glutathione. These three activities of human liver microsomes (TA
      5-hydroxylation, covalent binding of TA and TAI metabolites) seem dependent on
      the same cytochrome P450 of the IIC subfamily, since (i) antibodies against human
      liver cytochromes P450 IIC strongly inhibit these three activities, (ii) there is
      a clear correlation between these activities in various human liver microsomes,
      and (iii) TA acts as a competitive inhibitor for TAI activation into
      electrophilic metabolites (Ki approximately equal to 25 microM) and TAI inhibits
      TA 5-hydroxylation. However cross inhibition experiments indicate that tienilic
      acid hydroxylation and mephenytoin hydroxylation, a typical reaction of some
      human liver P450 IIC isoenzymes, are not catalysed by the same member of the P450
      IIC subfamily.

PMID- 1997004
TI  - In vitro inhibition of cell growth of MOLT-4 malignant human T-lymphoblasts by
      coenzyme F420.
AB  - The inhibitory effect of methanogenic coenzymes on the proliferation of MOLT-4
      human malignant T-lymphoblasts was tested. Furthermore the effects of
      methanogenic coenzymes on dihydrofolate reductase activity (DHFR) from chicken
      liver have been examined. The results showed that heat-stable extracts of the
      hydrogenotrophs Methanobacterium thermoautotrophicum, Methanoculleus
      thermophilicum and Methanogenium tationis inhibit both proliferation of human T
      lymphoblasts and DHFR activity. Heat-stable extract of the methylotroph
      Methanosarcina barkeri showed neither inhibitory nor stimulatory effects in both
      test systems. The present study proves coenzyme F420 to be the active, inhibitory
      component in methanogenic extracts.

PMID- 1997005
TI  - Cellular toxicity of sulfamethoxazole reactive metabolites--I. Inhibition of
      intracellular esterase activity prior to cell death.
AB  - Reactive metabolites produced by oxidative metabolism of the parent compound are
      considered responsible for the toxicity of a number of drugs, including
      idiosyncratic reactions to sulfonamide antibiotics. Using sulfamethoxazole
      hydroxylamine (SMX-HA) as a model compound, we report the use of a pH-sensitive
      fluorescent probe, 2',7'-biscarboxyethyl-5(6)-carboxyfluorescein (BCECF), to
      identify early subcellular targets of chemically synthesized, toxic drug
      metabolites in peripheral blood mononuclear cells. When toxicity was assessed
      with this probe immediately after a 2-hr drug challenge, SMX-HA produced a
      concentration-dependent decrease in cellular fluorescence which was not
      accompanied by the development of compromised cell membrane integrity until 18 hr
      later. Dissipation of pH gradients across the cell membrane with nigericin and
      monensin demonstrated that decreased intracellular pH was only a small component
      of SMX-HA-induced toxicity. Loading cells with BCECF 30 min prior to SMX-HA
      challenge produced only a 3% decrease in cellular fluorescence at an SMX-HA
      concentration of 1 mM, whereas addition of BCECF after drug challenge resulted in
      a 71% decrease in fluorescence, consistent with a direct drug effect on cellular
      esterase activity. This was confirmed by monitoring BCECF cleavage in cell
      lysates in the presence and absence of SMX-HA. These studies demonstrate that
      inhibition of cellular esterase activity accounted for the observed loss of
      cellular fluorescence after drug exposure. Since changes in cellular fluorescence
      at 2 hr correlated well with cell death at 18 hr, we conclude that SMX-HA
      inhibition of intracellular esterase activity is an early event in the process
      that terminates in metabolite-induced cell death.

PMID- 1997006
TI  - Cellular toxicity of sulfamethoxazole reactive metabolites--II. Inhibition of
      natural killer activity in human peripheral blood mononuclear cells.
AB  - Based on the identification of intracellular esterase activity as one early
      target of sulfamethoxazole hydroxylamine (SMX-HA), we wished to determine if the
      metabolite affected immune functions which involve esterases. The natural killer
      (NK) activity of human peripheral blood mononuclear cells (PBMC) was assessed
      with a cell concentration fluorescence technique following exposure to SMX-HA.
      When K562 target cells were incubated (4 hr/37 degrees) with various ratios of
      untreated PBMC effector to K562 target cells (E:T), NK activity increased from
      17.8 +/- 3.1% (mean +/- SEM; N = 12) at an E:T ratio of 5:1 to 46.2 +/- 2.0% at
      an E:T ratio of 40:1. Pretreatment of fresh PBMC with 0.1 to 1.0 mM SMX-HA
      produced a concentration-dependent inhibition of NK activity (E:T ratio 40:1)
      reaching approximately 80% at 1 mM SMX-HA. Maximum suppression of NK activity was
      completed within a 60-min pretreatment period with measurable inhibition detected
      within 30 min. The viability of effector cells was not affected by the metabolite
      during the pretreatment period. Therefore, the SMX-HA effects could not be
      directly attributed to decreased viability of the effector cells; they were
      irreversible and could be prevented by the inclusion of exogenous reduced
      glutathione (GSH) in a concentration-dependent manner. Given the important roles
      of NK cells in immune responsiveness and host resistance, our findings of rapid
      functional inactivation of the cytolytic effector function provide a possible
      link between idiosyncratic drug toxicity and drug effects directly on components
      of the immune system.

PMID- 1997007
TI  - Characteristics of induction of peroxisomal fatty acid oxidation-related enzymes
      in rat liver by drugs. Relationships between structure and inducing activity.
AB  - To clarify the mechanism of induction of hepatic peroxisome-associated enzymes by
      drugs, we examined the interrelationship between the structures of fifteen drugs
      of two types (phenoxyacetic acid derivatives and perfluorinated compounds) and
      their inducing activities. Male Wistar rats were given the drugs at 150 mg/kg
      body weight daily for 2 weeks, and then hepatic activities of fatty acid
      metabolism-related enzymes were determined. The activity of the cyanide
      insensitive fatty acyl-CoA oxidizing system located in peroxisomes was increased
      significantly in the following order: 2,4,5-trichlorophenoxypropionic acid (12.5
      fold) greater than 2,4-dichlorophenoxypropionic acid (6.6-fold) greater than
      clofibrate (4.5-fold) greater than 2-methyl-4-chlorophenoxyacetic acid (2.6-fold)
      greater than 2,4,5-trichlorophenoxyacetic acid (2.5-fold) greater than p
      chlorophenoxypropionic acid (2.4-fold) greater than 2,4-dichlorophenoxyacetic
      acid (1.7-fold). Treatment with perfluorinated compounds, perfluorobutyric acid,
      perfluorooctanoic acid, perfluorodecanoic acid and perfluorooctanol, also induced
      the activity by 2-, 4.3-, 3.1- and 2.0-fold respectively. The profile of the
      induction of carnitine acetyltransferase by these compounds was quite similar to
      that of cyanide-insensitive fatty acyl-CoA oxidizing system. Lipophilicity of
      these drugs was determined by the octanol-water partition method. Among these
      drugs, 2,4,5-trichlorophenoxypropionic acid showed the largest octanol/water
      partition coefficient (log P = 0.39). These results show a strong correlation
      among the number of chlor-substitutions on the phenyl moiety, the methyl-group on
      the alpha position of the acetic acid moiety, lipophilicity and the inducibility
      of peroxisomal fatty acid oxidation-related enzymes.

PMID- 1997008
TI  - Inhibition of tryptophan hydroxylase by benserazide and other catechols.
AB  - Tryptophan hydroxylase (L-tryptophan, tetrahydropteridine:oxygen oxidoreductase
      [5-hydroxylating]; EC 1.14.16.4; TPH), the initial and rate-limiting enzyme in
      the biosynthesis of the neurotransmitter serotonin, was inhibited directly by
      benserazide, an inhibitor of aromatic-L-amino-acid decarboxylase (3,4-dihydroxy-L
      phenylalanine carboxy-lyase; EC 4.1.1.28; AAAD). Benserazide was a competitive
      inhibitor for the pterin cofactor tetrahydrobiopterin and an uncompetitive
      inhibitor for the substrate tryptophan. NSD 1015, another decarboxylase
      inhibitor, did not directly inhibit TPH. Other compounds with catechol moieties
      in their structures such as 3,4-dihydroxyphenylalanine (DOPA), dopamine,
      apomorphine, and SKF 38393 were also found to be potent inhibitors of TPH. These
      results indicate that drugs or neurotransmitters with catechol structures
      directly inhibit the activity of TPH and add to a growing body of evidence
      indicating that endogenous dopamine can exert untoward effects on serotonin
      neurons, including inhibition of TPH. Furthermore, the use of decarboxylase
      inhibitors to cause the accumulation of 5-hydroxytryptophan as an in vivo measure
      of TPH activity could be problematic, particularly when drugs with catechol
      structures or dopamine-releasing compounds are also administered.

PMID- 1997009
TI  - Glutathione depletion in human and in rat multi-drug resistant breast cancer cell
      lines.
AB  - The effects of GSH depletion in a human breast cancer cell line and a multi-drug
      resistant subline (ADRr) were determined in a number of experimental conditions.
      The ADRr cells contained lower GSH concentration which cannot be explained solely
      on the basis of differences in cell kinetics, and yet the rate-limiting synthetic
      enzyme gamma-glutamylcysteine synthetase was increased 2-fold. Inhibition of GSH
      synthesis by BSO resulted in more rapid and more pronounced GSH depletion in ADRr
      compared to the wild-type cells, suggesting that enhanced GSH utilization and
      efflux in the resistant cells account for the lowered basal concentration. In
      addition, the gamma-glutamyl moiety salvage enzyme gamma-glutamyltranspeptidase
      was reduced markedly in the ADRr cell line. Since these cells have overexpression
      of the efflux pump protein P-glycoprotein, we examined the effects on cellular
      GSH of inhibition of the pump's function by verapamil. We found that verapamil
      significantly depleted cellular GSH. In a rat mammary carcinoma cell line
      selected in Adriamycin for multi-drug resistance, a similar molecular phenotype
      has been described including diminished cellular GSH concentration. Verapamil
      treatment of these cells also resulted in significant depletion of cellular GSH.
      These results are consistent with the recent report that combined treatment of
      BSO and verapamil has an additive effect on cytotoxicity. It is likely that
      decreased basal GSH concentration is due to oxidation and conjugation of it in
      reactions catalyzed by the enhanced peroxidase and GST found in these cells.

PMID- 1997010
TI  - A comparison of levels of glutathione transferases, cytochromes P450 and
      acetyltransferases in human livers.

PMID- 1997011
TI  - Effects of various tetracycline derivatives on in vitro and in vivo beta
      oxidation of fatty acids, egress of triglycerides from the liver, accumulation of
      hepatic triglycerides, and mortality in mice.

PMID- 1997012
TI  - The relationship between nuclear glutathione levels and resistance to melphalan
      in human ovarian tumour cells.

PMID- 1997013
TI  - Thyroid hormone-independent regulation of mitochondrial glycerol-3-phosphate
      dehydrogenase by the peroxisome proliferator clofibric acid.

PMID- 1997014
TI  - Review of clinical experience with digoxin immune Fab (ovine).
AB  - Following the development of methods for eliciting and purifying digoxin-specific
      Fab fragments with high affinity and specificity for cardiac glycosides, clinical
      studies were undertaken as a multicenter, open-label trial to test safety and
      efficacy in patients with advanced and potentially life-threatening digitalis
      toxicity that failed to respond to conventional therapeutic measures. One-hundred
      fifty such patients were treated with digoxin-specific antibody fragments
      purified from immunoglobulin G (IgG) produced in sheep. Doses of Fab were
      equivalent to the amount of digoxin or digitoxin in the patient's body, as
      estimated from the medical history or serum concentration measurements. Of 150
      patients included in this trial, detailed information is available on 148. One
      hundred nineteen (80%) had resolution of all signs and symptoms of digitalis
      toxicity following specific Fab fragment infusions, 14 (10%) improved, and 15
      (10%) showed no response. Among 14 patients with adverse events possibly or
      probably caused by Fab, the most common events were development of hypokalemia
      and exacerbation of congestive heart failure. Analysis of the available clinical
      data indicates that a treatment response was observed in at least 90% of patients
      with convincing evidence of advanced and potentially life-threatening digitalis
      toxicity. The data from this multicenter trial have been augmented by findings
      from an observational surveillance study conducted to monitor the safety and
      effectiveness of treatment with digoxin immune Fab (ovine) following commercial
      availability. In this experience, 74% of patients were judged to have a complete
      or partial response to treatment, and 12% no response. The response for the
      remaining 14% was not reported or reported as uncertain. In this clinical
      experience, digoxin-specific Fab was generally well tolerated and clinically
      effective in patients with potentially life-threatening digitalis toxicity.

PMID- 1997015
TI  - Risk factors and manifestations of digoxin toxicity in the elderly.
AB  - The incidence of digoxin toxicity increases with age, largely because the two
      most common conditions that benefit from use of digoxin, congestive heart failure
      and atrial fibrillation, are markedly more prevalent in old age. Whether the
      elderly are more sensitive to the effects of digoxin because of age per se is
      unclear. However, several other factors render the elderly more susceptible to
      digoxin toxicity. These include an age-related decline in renal function and a
      decrease in volume of digoxin distribution. There is also an increase in the
      number of comorbid conditions, including cardiovascular and chronic obstructive
      pulmonary disease, which heighten susceptibility to digoxin toxicity. Moreover,
      treatment of these diseases with such interactive medications as quinidine and
      calcium channel blockers may increase the serum level of digoxin. Similarly, such
      electrolyte imbalances as hypokalemia and hypomagnesemia occur more frequently in
      the elderly as a result of diuretic therapy. However, recent data suggest that
      manifestations of digoxin toxicity among younger and older patients do not
      differ. Similar incidences of cardiac toxicity, gastrointestinal toxicity, and
      altered mental status are found in both patient populations. Treatment of
      digitalis toxicity in the elderly is the same as for younger patients. Response
      rates to Digibind are not diminished in the elderly.

PMID- 1997016
TI  - Results of multicenter studies of digoxin-specific antibody fragments in managing
      digitalis intoxication in the pediatric population.
AB  - Digitalis toxicity continues to be a problem for pediatric patients undergoing
      therapy with cardiac glycosides for heart failure or arrhythmias, as well as in
      accidental ingestions. In this article the previous use of digoxin-specific
      antibody Fab fragments to treat digitalis overdose or intoxication in children is
      reviewed. The case reports cited in the medical literature and the 57 pediatric
      cases gathered as a result of the multicenter clinical trial and postmarketing
      surveillance study reported here indicate that digoxin-specific antibody Fab
      fragments are effective in ameliorating signs of digitalis poisoning in children.
      Not only can Fab fragments rapidly eradicate potentially life-threatening
      arrhythmias and conduction defects, but they are also effective in treating
      hyperkalemia and other noncardiac manifestations of digitalis toxicity. In the
      small samples of patients studied to date, complications have been minimal and no
      allergic reactions to digoxin-specific Fab fragments have been observed.
      Recommendations for the management of digitalis intoxication in children are
      outlined.

PMID- 1997017
TI  - Experience with digoxin immune Fab (ovine) in patients with renal impairment.
AB  - Digibind is a purified antigen binding fragment (Fab) of immunoglobulin G
      antibodies raised to bind digoxin. Studies in animals suggest renal excretion
      accounts for a substantial portion of Fab's elimination. Thus it is expected that
      elimination of antidigoxin Fab fragments would be prolonged in patients with
      renal impairment; it remains unclear whether digoxin might be released with
      possible recurrence of toxicity. To shed light on this potential for recrudescent
      digitalis toxicity following release of bound digoxin, the author scrutinized the
      records of patients with impaired renal function who were treated with Digibind.
      Data are available from three sources: the original multicenter investigation of
      Digibind in 150 patients with life-threatening digoxin or digitoxin toxicity, a
      postmarketing surveillance study of 745 patients treated with Digibind, and all
      other reports in the literature or to Burroughs Wellcome Co of physician
      experience with any antidigoxin Fab. Sixty percent of patients in the multicenter
      trial and 80% of patients in the postmarketing surveillance trial had some degree
      of renal impairment. Patients with poor renal function had no evidence of
      decreased effectiveness or safety either in terms of percent of patients
      responding, onset of effect or evidence of recrudescence. From all sources the
      authors identified 28 patients treated with Fab who were functionally anephric.
      Twenty-seven of these patients had no evidence of recrudescent toxicity. One
      patient was reported to have complete resolution of digoxin-induced third-degree
      atrioventricular (AV) block, but AV block recurred 10 days after Fab treatment
      and persisted for 10 days thereafter. Although this case offers the only clinical
      evidence suggesting recrudescence can occur, there were no likely alternative
      explanations for the clinical findings.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1997018
TI  - Which cardiac disturbances should be treated with digoxin immune Fab (ovine)
      antibody?
AB  - Digoxin excess can produce characteristic bradyarrhythmias, tachyarrhythmias, and
      hyperkalemia. The bradyarrhythmias, which consist of disturbances in conduction
      and block at the level of the atrioventricular and sinus nodes, are mediated by a
      direct and vagotonic effect. The vagotonic effect of excess digoxin may also
      result in a marked slowing of the sinus rate in the setting of severe toxicity.
      Digoxin increases automatic and triggered electrical activity in atrial muscle,
      His-Purkinje system, and ventricular muscle, which predisposes to tachycardias.
      Many of the tachyarrhythmias are relatively specific for the toxic effects of
      digoxin. Atrial tachycardias with variable atrioventricular block, accelerated
      junctional rhythms (especially in the setting of atrial fibrillation), and
      fascicular tachycardias are characteristic digoxin toxic rhythms. Digoxin
      specific antibody fragments should be considered the treatment of choice for any
      digoxin toxic arrhythmia associated with hemodynamic compromise or the threat of
      hemodynamic compromise. Hyperkalemia, when due to acute severe digoxin toxicity,
      is also an appropriate indication for digoxin-specific Fab fragment therapy. When
      assessing the risk:benefit ratio for using digoxin-specific Fab fragment therapy,
      one needs to determine, in addition to the electrocardiographic manifestations
      and patient's hemodynamic status (1) the severity of toxicity, as indexed by the
      amount ingested and/or the serum digoxin concentration; (2) the expected time
      course for reversal of toxicity, which is usually determined by the status of
      renal function; (3) the need for digoxin to provide ventricular rate control or
      improved ventricular contractility and therapeutic alternatives to digoxin; (4)
      the presence of a strong allergy history; (5) the presence of such factors as
      increased age and severity of heart disease that may predispose to digoxin
      toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1997019
TI  - Recognition and management of digitalis intoxication: implications for emergency
      medicine.
AB  - Digitalis intoxication is among the most common serious adverse drug reactions in
      clinical medicine. While the recent development of a radioimmunoassay to
      accurately measure serum concentrations of digoxin has been of assistance,
      digitalis intoxication remains a difficult diagnosis to make with certainty. The
      difficulty in diagnosing digitalis intoxication arises from the nonspecificity of
      its associated signs and symptoms. The most common symptoms include fatigue,
      weakness, nausea, and anorexia. These symptoms can occur with many illnesses
      other than digitalis intoxication. Similarly, the electrocardiographic
      disturbances caused by cardiac glycosides may be nondiagnostic. The arrhythmias
      commonly associated with digitalis toxicity are often nonspecific and can be a
      reflection of the patient's underlying heart disease. The measurement of serum
      digoxin levels is useful, but studies have demonstrated overlap of the levels
      between groups with and without toxicity. Due to the modulation of the cardiac
      effects of digitalis glycosides by such clinical variables as underlying
      myocardial or renal disease, electrolyte and acid-base imbalances, and other
      factors, the correlation of toxicity with particular serum digoxin concentrations
      may vary. Because of the inherent difficulties in confirming the diagnosis of
      digitalis intoxication in some cases, digoxin-specific Fab antibodies may play a
      role as a diagnostic tool. Certainly, digoxin-specific Fab antibodies play a
      significant part in the treatment of digitalis intoxication. Fab antibodies have
      been successfully used to reverse the effects of digoxin, digitoxin, and oleander
      poisoning. These antibodies are useful in the treatment of acute and chronic
      digitalis intoxication in all age groups, including geriatric and pediatric
      populations.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1997020
TI  - Allergic histories and reactions of patients treated with digoxin immune Fab
      (ovine) antibody. The Digibind Study Advisory Panel.
AB  - Seven hundred seventeen adult patients with life-threatening digitalis
      intoxication were treated with Fab fragments of ovine antidigoxin immunoglobulin
      G (IgG). Results of the efficacy of treatment and adverse effects were collected
      with standard report forms. Eighty-two (11%) of the patients were recorded as
      having histories of allergy (71 patients) and/or asthma (11 patients). Of the
      "allergic" subjects, 35 described reactions to antibiotics, 19 to other
      medications, 3 to foods, and 2 to pollens; in 12 subjects the etiologic agent was
      not specified. Six subjects had adverse reactions that were probably or possibly
      due to allergy to components of the antibody preparation. Of these 4 (5%; 95%
      confidence interval (Cl) 1.8% to 12%) occurred in the 82 subjects with histories
      of allergy or asthma and 3 (9%; 95% Cl 1.8% to 23%) of these occurred in the 35
      persons with histories of allergy to an antibiotic. In contrast, only 2 (0.3%;
      95% Cl 0.04% to 1.1%) similar reactions occurred in the 635 subjects with no
      histories of allergy or asthma. All reactions responded to symptomatic treatment.
      The authors conclude that treatment of digitalis intoxication with ovine
      antidigoxin IgG-Fab (Digibind) is generally well tolerated and allergic reactions
      are rare. However, there is a significantly increased risk of reactions in
      patients with histories of allergy or asthma.

PMID- 1997021
TI  - Training physician-scientists for the 1990s.
AB  - The author describes a paradox: on the one hand, remarkable strides have been
      made in biomedical research that have created unparalleled opportunities for
      progress in the understanding, prevention, and treatment of human diseases; yet
      on the other hand, too few people are being adequately trained to actualize the
      promise of these advances. Concerns that have been raised in the past concerning
      the training of physician-scientists are reviewed and general statements are made
      about their current availability. The status and health of M.D.-Ph.D. programs
      are discussed, because many think this kind of program is an important mechanism
      for training the biomedical researchers of the future. New initiatives under way
      to encourage careers in research are considered and recommendations are made for
      the future support of research training and encouragement of the exceptional
      young people who are entering the research pipeline.

PMID- 1997022
TI  - Ownership of research data.
AB  - The author reviews the conventional "works for hire" principle that an
      institution, not its employees, owns the rights to its employees' written
      products or other forms of expression, including primary research data. This
      principle is not open to debate as a legal matter. The tough problems giving rise
      to debates regarding data ownership and access are ethical problems rather than
      legal ones; these will remain unsettled for some time because at present there is
      no consensus concerning what constitutes ethical conduct among scholars and
      scientists and how seriously and in what manner to penalize breaches of that
      conduct. Access to data is a thorny issue; case histories illustrate the legal
      and ethical difficulties involved in questions of who has access to information
      compiled in the course of academic inquiry, and for what purpose. Much depends on
      the ethics and established procedures of the employing institution, but current
      case law suggests that a faculty member or institutional researcher does not have
      any legal right to review the data developed by a colleague. The author
      recommends that institutions clearly state their policies regarding ownership of
      data, and presents guidelines for such a policy.

PMID- 1997023
TI  - An academic medical center's experience with mandatory managed care for Medicaid
      recipients.
AB  - This paper reports on The Hospital of the University of Pennsylvania's experience
      and concerns as a participating primary care site in a Medicaid managed care
      program (HealthPASS), which was established in 1986. Enrollment is mandatory for
      approximately half of Philadelphia's medical assistance population. Participating
      primary care sites receive monthly capitation for enrollees and serve as
      "gatekeepers" for specialty and inpatient services. The report discusses why the
      academic medical center chose to participate in the program and how existing
      activities were modified to meet both increased demand for primary care and
      increased administrative requirements. It also identifies characteristics of the
      HealthPASS program and of the medical center that have impeded effective case
      management of care for the urban poor population that the program serves.
      Improving the quality of care for the medically indigent while controlling costs
      is essential, but political realities and the special needs of the Medicaid
      population must be acknowledged. Increased attention must be given to the impact
      that political compromises have on the design and effectiveness of a managed care
      program.

PMID- 1997024
TI  - Integrative virology for senior medical students.

PMID- 1997025
TI  - A characterization of the imminent leadership transition in academic family
      medicine.
AB  - Of the 106 identified chairmen of academic departments, divisions, or sections of
      family medicine in the United States in 1990, 97 (92%) responded to a survey
      designed to characterize the current chairmen of family medicine and estimate
      requirements for future chairmen. Even though 43% had occupied the chair for less
      than five years, over half, not limited to older chairmen, intended to leave
      within five years. Reasons for leaving varied, including being required to leave,
      career choice, personal reasons, and especially dissatisfaction with the job.
      Only half of current chairmen identified one or more qualified applicants for
      chairmanship within their own departments. The formal training and experience of
      these potential chairmen strongly resembled the training and experience of
      current chairmen, especially the fact that they had little training or experience
      in research. In the 1990s, the demand for academic chairmen of family medicine is
      likely to be large, the competition for capable candidates keen, and the
      challenges great for new chairmen, who will probably be young, residency-trained
      family physicians with relatively limited academic experience.

PMID- 1997026
TI  - Comparing the case materials available from a teaching hospital's autopsies in
      1968 and 20 years later.
AB  - The Accreditation Committee on Graduate Medical Education requires both
      sufficient volume and variety of necropsy material for training in anatomic
      pathology. Since the number of autopsies has declined markedly in the last 20
      years, the author sought to determine whether the variety of case material
      available from the autopsies performed at his teaching hospital had changed
      during that time span. Major diagnoses were abstracted from the reports of 200
      autopsies of adults performed in 1968 and from a period 20 years later (1987,
      1988, and part of 1989). Comparison between the two eras' diagnoses revealed very
      few changes in the incidences of various diseases. This was true even though the
      racial mix of patients had changed markedly. While declining autopsy rates are of
      concern, this study suggests that medical educators may not need to be concerned
      over the variety of autopsy case material. The author makes several suggestions
      for maximizing the teaching impact of each autopsy.

PMID- 1997027
TI  - Career choices of graduates from Washington University's Medical Scientist
      Training Program.
AB  - The Medical Scientist Training Program at Washington University has been in
      existence for 21 years; by 1990, 148 students had completed the program leading
      to the combined M.D./Ph.D. degree. Of these graduates, most (95%) chose to enter
      residency programs rather than postdoctoral fellowships. Of the 72 who had
      completed their residencies or postdoctoral training by 1990, the vast majority
      (89%) reported that they were returning to academic institutions or the National
      Institutes of Health. Those in academic institutions were primarily in clinical
      departments, with medicine being the first choice. Most said they were devoting
      much of their time to basic research. These graduates were progressing rapidly
      into tenured positions and appear to have been well funded.

PMID- 1997028
TI  - Substance abuse by anesthesiology residents.
AB  - A 1989 cross-sectional substance abuse survey of 260 former anesthesiology
      residents of the Medical College of Wisconsin (MCW) during the previous 30 years
      yielded 183 responses (70.3%). Over three-fourths (77.2%) of those who responded
      reported that they had used alcohol when they were residents; 20.0% had used
      marijuana; and 15.7% had used cocaine. Forty-three of the 178 respondents had
      used unprescribed psychoactive drugs. Twenty-nine (15.8%) had been self-admitted
      problematic substance abusers during their residencies: 23, alcohol dependent and
      six, drug dependent; among the latter were four with a dual (alcohol and drug)
      dependency. More than 85% considered the drug policy information available during
      their residencies had been inadequate; institutional drug-control policies were
      rated "fair-to-poor" by more than 70%. Thirty-five of the residents had observed
      their teachers using alcohol and/or other drugs to the detriment of their
      teaching; approximately one-third of these infractions had gone unreported.

PMID- 1997029
TI  - A classification of developmental activities of academic family medicine
      supported by federal grants.
AB  - Substantial funds have been awarded to academic departments of family medicine
      through the federal Establishment of Departments of Family Medicine grants
      program, initiated in 1980 under the Public Health Service Act. In 1989 the
      authors analyzed the successful grant applications in a sample of 61 institutions
      variously funded or re-funded for the grant cycles from 1980 through 1986 in
      order to classify the supported developmental activities. Three dimensions for
      explicating this activity emerged: (1) the functional area of the activity (e.g.,
      curricular development); (2) the objectives of the activity (e.g., improving
      relevance of instruction); and (3) the strategies to be used to attain the
      objectives (e.g., addition of specialized faculty). This classification scheme
      provides a tentative but useful framework for characterizing departmental
      development.

PMID- 1997030
TI  - Influence of effective communication by surgery students on their oral
      examination scores.
AB  - This study investigated the influences of specific elements of surgery students'
      verbal and nonverbal communication on evaluators' "objective" ratings of several
      categories of the students' performances on oral examinations. Three actors and
      two actresses, dressed as surgery students in a wide range of attire, were
      videotaped as they reenacted five transcripts of actual students' responses in
      their oral examinations. For each examination, the actors portrayed the students'
      responses to the same examining surgeon in two formats, one using direct eye
      contact with a moderate response rate (Style A) and the other using indirect eye
      contact with a slower response rate (Style B). All transcripts were taped at
      least twice. The resulting 255 videotaped "examinations" were randomly
      distributed in 1988 to 78 clinical surgery faculty representing 46 institutions
      throughout the United States and Canada. These faculty viewed the reenactments
      (under the impression they were actual examinations) and rated the "students"
      performances overall and in ten categories concerning different aspects of the
      students' knowledge, clinical decision-making skills, and personal
      characteristics. The performances done in Style A were rated significantly higher
      than those done in Style B (1) in every performance category except decision
      making and (2) when the scores were classified by the content of the responses
      and how professionally dressed the students were. There were also a significant
      relationship between scores on communication skills and the overall all scores on
      examinations. These findings suggest that regardless of the content of a
      student's responses on an oral examination, evaluators are strongly influenced by
      how well the student communicates.

PMID- 1997031
TI  - A multidisciplinary program to improve the teaching skills of incoming
      housestaff.
AB  - Residents at the School of Medicine and Biomedical Sciences at the State
      University of New York at Buffalo (SUNY at Buffalo) expressed an interest in
      receiving instruction in teaching skills. In 1988, under sponsorship of the
      Graduate Medical-Dental Education Consortium, faculty and residents implemented
      an orientation program for 110 incoming housestaff. Residents received
      instruction in large-group teaching skills, bedside teaching, small-group
      discussion, and student evaluation. The program was rated positively by the
      residents, 5% of whom became instructors in the orientation program for the
      following year. Because of the program's structure, both faculty and housestaff
      receiving training in teaching skills, which may lead to an overall improvement
      in the teaching of SUNY at Buffalo's medical students.

PMID- 1997032
TI  - Comparing the medical school curricula followed by students in an independent
      study program and a traditional one.
AB  - This 1988 retrospective study examined the medical school curricula followed by
      students from two classes using two curricular styles at one medical school. By
      consulting school records, the authors ascertained the courses actually taken,
      the number of weeks that students actually devoted to them, and the sequence of
      courses, both for those students following an independent-study curriculum and
      for those following a traditional one. These data were compared with the
      corresponding data concerning the traditional curriculum requirements to
      determine whether the curricula the students actually followed, in either style,
      showed any marked difference from the required curriculum. The findings showed
      that the curricula followed by the independent-study students deviated
      considerably from both the requirements of the traditional curriculum and also
      the actual curricula followed by the students using the traditional curriculum,
      who almost never chose to deviate from the requirements. The independent-study
      students showed considerable intragroup variation in the ways they organized
      their curricula, most commonly in eliminating selected formal clerkship or
      specialty medicine courses, or altering the duration of clerkships. Elective
      coursework was substituted for formal clerkship experiences in the majority of
      cases where clerkship courses were eliminated.

PMID- 1997033
TI  - Physiatric research: a hands-on approach.

PMID- 1997034
TI  - WDA complaint resolution mechanism.

PMID- 1997035
TI  - Alice in Wonderland: a closer look at the bewildering world of UCR.

PMID- 1997036
TI  - Dental record offers new products.

PMID- 1997037
TI  - Splinting of compromised teeth with composite resin.

PMID- 1997038
TI  - American Society for Laser Medicine and Surgery. Eleventh Annual Meeting. San
      Diego, California, April 29-May 1, 1991. Abstracts.

PMID- 1997039
TI  - Casein kinase I and II--multipotential serine protein kinases: structure,
      function, and regulation.

PMID- 1997040
TI  - Signaling mechanisms in microorganisms: common themes in the evolution of signal
      transduction pathways.

PMID- 1997041
TI  - Transmembrane signal transduction pathways in Dictyostelium.

PMID- 1997042
TI  - The regulation of ciliary motility in Paramecium by Ca2+ and cyclic nucleotides.

PMID- 1997043
TI  - Aspirin and extradural blocks.

PMID- 1997044
TI  - Disposition of morphine-6-glucuronide and morphine in healthy volunteers.
AB  - The pharmacokinetics and subjective side effects of i.v. morphine sulphate 120
      micrograms kg-1 and morphine-6-glucuronide (M6G) 30 micrograms kg-1 were
      determined in six healthy volunteers, using a placebo-controlled, single-blind
      randomized crossover design. Five of these volunteers underwent an additional
      (non-randomized) study of M6G 60 micrograms kg-1. Subjective side effects were
      similar following both drugs, but of shorter duration following M6G. Morphine was
      not detected after administration of M6G. For M6G 30 micrograms kg-1 the mean
      (SD) volume of distribution, elimination half-life and clearance were 29.38
      (18.36) litre, 2.05 (1.2) h and 187.81 (37.41) litre h-1, respectively. These
      values were not significantly different from those obtained for M6G 60 micrograms
      kg-1. In all subjects the volumes of distribution and clearances were
      significantly smaller for M6G than for morphine, but the elimination half-lives
      were similar.

PMID- 1997045
TI  - Effect of clonidine on the circulation and vasoactive hormones after aortic
      surgery.
AB  - After completion of abdominal aortic graft, 29 patients received an i.v. infusion
      of placebo (n = 16) or clonidine 7 micrograms kg-1 (n = 13) over 120 min in a
      double-blind study. Cardiovascular variables were measured and plasma samples
      obtained up to 5 h after arrival in the recovery room, for assay of
      noradrenaline, adrenaline, vasopressin and renin concentrations. Noradrenaline,
      adrenaline and vasopressin concentrations decreased in the clonidine group
      throughout recovery (P less than 0.001, 0.05 and 0.05, respectively, vs placebo).
      Heart rate was less in the clonidine group (P less than 0.01). There was no
      significant difference in mean arterial pressure between groups. Stroke volume
      was larger (P less than 0.01) and there were fewer episodes of hypertension (P
      less than 0.05) and tachycardia in the clonidine group. In addition, a reduction
      in the number of circulatory interventions (P less than 0.05) and episodes of
      shivering was noted in the clonidine group. Mean (SD) postoperative volume
      requirements were larger in the clonidine group (total postoperative input:
      clonidine 1462 (604) ml; placebo 1064 (348) ml (P less than 0.05]. These data are
      consistent with the observation that clonidine modifies endocrine and circulatory
      status after major surgery.

PMID- 1997046
TI  - Metoclopramide and renal vascular resistance.
AB  - We have studied the effect of i.v. metoclopramide on renal vascular resistance in
      nine healthy volunteers. Peak systolic and end-diastolic frequencies were
      measured using duplex Doppler ultrasound of a renal interlobar artery, before and
      after the administration of i.v. metoclopramide 10 mg, and the resistance index
      derived. There was no significant change in mean arterial pressure or resistance
      index following metoclopramide.

PMID- 1997047
TI  - Hypnotic and anaesthetic action of thiopentone and midazolam alone and in
      combination.
AB  - This study examined the interaction between i.v. administered midazolam and
      thiopentone on the loss of response to verbal command ("hypnosis") and the loss
      of response to transcutaneous electrical stimulation of the ulnar nerve
      ("anaesthesia") in patients presenting for minor elective surgery. Dose-response
      curves for thiopentone and midazolam individually and in combination were
      determined using the two end-points in 300 unpremedicated patients. For hypnosis
      a highly significant (P less than 0.001) supra-addictive (synergistic)
      interaction was found, the combination having 1.8 times the expected potency of
      the individual agents. Although midazolam failed to produce anaesthesia in the
      dose range used, the dose of thiopentone required to produce anaesthesia was
      reduced by 50% in the presence of midazolam. The mechanism of interaction and the
      potential role of benzodiazepine-barbiturate combinations are discussed and the
      observed synergistic anaesthesia interaction is used to explain the potentially
      dangerous combination of benzodiazepines with other potent CNS depressants such
      as barbiturates and alcohol.

PMID- 1997048
TI  - Interpleural regional analgesia: detection of the interpleural space by saline
      infusion.

PMID- 1997049
TI  - Anaesthetic management of a 2-month-old infant for laser resection of vocal cord
      granuloma.
AB  - A 2-month-old infant underwent excision of granulomata of vocal cords with a
      carbon dioxide laser. High frequency jet ventilation was given through a surgical
      metal suction tube during the operation. The anaesthetic technique for the infant
      and the problems of the use of carbon dioxide laser in laryngeal surgery are
      discussed.

PMID- 1997050
TI  - Muscle biopsy for diagnosis of malignant hyperthermia susceptibility in two
      patients with severe exercise-induced myolysis.
AB  - Muscle biopsy and in vitro contracture tests for diagnosis of susceptibility to
      malignant hyperthermia (MH) were performed in two patients who had developed
      fever and severe myolysis during exercise. MH susceptibility was confirmed in one
      patient, but in the other, exercise-induced heat stroke proved to be the correct
      diagnosis. Clinical presentation and epidemiology of exercise-induced MH and its
      relation to the heat stroke syndrome are discussed.

PMID- 1997051
TI  - Anaesthesia for simultaneous caesarean section and clipping of intracerebral
      aneurysm.

PMID- 1997052
TI  - 29-gauge spinal needles.

PMID- 1997053
TI  - Chest physiotherapy.

PMID- 1997054
TI  - Temazepam absorption in patients before surgery.
AB  - We have compared the rates of absorption and efficacies of temazepam 30 mg in
      elixir and capsule formulations in 100 patients before surgery. Both formulations
      provided anxiolysis and sedation, but there was wide variation in plasma
      concentrations of temazepam between individuals and between formulations. The
      presence or absence of anxiety did not influence the absorption of the
      preparations. It is suggested that plasma concentrations in excess of 200 ng ml-1
      are required for sedation and anxiolysis, and that this may be achieved more
      reliably using the elixir formulation.

PMID- 1997055
TI  - Plasma concentrations of bupivacaine and two of its metabolites during continuous
      interscalene brachial plexus block.
AB  - An interscalene brachial plexus block was performed via a catheter with 20-28 ml
      of 0.75% bupivacaine plus adrenaline for surgery of the shoulder region in 12
      patients. Constant infusion of 0.25% bupivacaine 0.25 mg kg-1 h-1 was continued
      for 24 h. During surgery light general anaesthesia, without analgesics, was
      maintained. Plasma concentrations of total and unbound (free fraction)
      bupivacaine, desbutylbupivacaine (DBB), 4-hydroxybupivacaine (4-OHB) and alpha 1
      acid glycoprotein (AAG) were measured at predetermined intervals during the
      continuous block. The greatest mean plasma concentrations of bupivacaine were
      measured at 30 min (1.63 (SD 0.55) micrograms ml-1) and 60 min (1.38 (0.48)
      micrograms ml-1). There was a small but statistically significant increase in the
      plasma concentration of bupivacaine between 12 and 24 h of infusion. The mean
      unbound concentration of bupivacaine in plasma decreased from 0.044 (0.015)
      microgram ml-1 (3.6 (1.1)% of total bupivacaine concentration) at 3 h to 0.023
      (0.011) micrograms ml-1 (2.1 (1.0)%) at 24 h. The AAG concentration in plasma
      increased by 38% in 24 h. The metabolites DBB and 4-OHB were detectable in plasma
      from 30 min, with a gradual increase during infusion. At 24 h the mean
      concentrations of DBB and 4-OHB were 0.33 (0.22) micrograms ml-1 and 0.13 (0.04)
      micrograms ml-1, respectively. There were no toxic reactions during the blocks.

PMID- 1997056
TI  - Comparison of extradural ropivacaine and bupivacaine.
AB  - Ropivacaine, a new long acting amide type local anaesthetic, was compared with
      bupivacaine in a randomized double-blind study. One hundred and ten patients
      undergoing extradural anaesthesia received a test dose of 3 ml of 1% lignocaine
      with adrenaline which was followed by 15 ml of one of five solutions: 0.5, 0.75
      or 1.0% ropivacaine or 0.5 or 0.75% bupivacaine. There was little difference
      between the groups with respect to speed of onset or sensory block. The duration
      of analgesia was increased by increasing the concentration of both drugs, but
      this had minimal effect on onset time or extent of block. When the same
      concentration of each drug was administered, there were inconsistent differences
      in duration of sensory block, none of which was statistically significant.
      Increasing concentration of both drugs resulted in greater degree and longer
      duration of motor block. Ropivacaine produced a slower onset, shorter duration
      and less intense motor block than the same concentration of bupivacaine. The
      cardiovascular changes were similar in all groups.

PMID- 1997057
TI  - Unexpected, difficult laryngoscopy: a prospective survey in routine general
      surgery.
AB  - A prospective study of unexpected, difficult laryngoscopy was carried out. During
      a 7-month period, all general surgery patients in whom the trachea was intubated
      were assessed; only those with obvious neck pathology were excluded. Ease or
      difficulty of laryngoscopy was graded by a standard method. There were no grade 4
      cases and no failed intubations in a total of 1387 cases. There were significant
      differences in the results recorded by different individuals; this did not
      correlate with seniority or with the type of surgery. Four factors have been
      identified which help to explain these discrepancies. These findings are analysed
      in relation to the training of junior staff, with particular reference to
      obstetric anaesthesia.

PMID- 1997058
TI  - Ingestion of clear fluids is safe for adolescents up to 3 h before anaesthesia.
AB  - We have studied the effect of ingestion of unlimited clear fluids by adolescents
      up to 3 h before anaesthesia to determine the effect this fluid ingestion would
      have on thirst, hunger and gastric contents at induction of anaesthesia. We
      studied prospectively 152 adolescents (ages 13-19 yr) undergoing elective
      surgery. Fifty percent of the patients had nothing by mouth after midnight. The
      other 50% were instructed to ingest unlimited clear fluids up to 3 h before
      surgery. On arrival in the operating room, subjects were asked to assess thirst
      and hunger with a linear analogue scale of 0-10 (0 corresponding to no thirst or
      no hunger). After induction of anaesthesia, gastric contents were aspirated via a
      16-French gauge orogastric tube. Gastric fluid volume (GV) was measured with a
      syringe and gastric pH (GpH) was assessed with Merck pH strips. GV, GpH and
      subject hunger were unaffected by ingestion of clear fluids. Subject thirst was
      reduced by clear fluids. It is concluded that unlimited clear fluid ingestion by
      healthy adolescents up to 3 h before operation decreases thirst and does not
      affect gastric contents.

PMID- 1997059
TI  - Pharmacokinetics and clinical experience of 20-h infusions of methohexitone in
      intensive care patients with postoperative pyrexia.
AB  - We have studied the pharmacokinetics of 20-h infusions of methohexitone in young
      patients with postoperative fever undergoing artificial ventilation of the lungs.
      The infusion rate was adjusted so that patients were unresponsive to vocal
      stimulation but reacted to tracheal suction. The mean steady state concentration
      of methohexitone required was 2.6 mg litre-1 (unbound 0.53 mg litre-1). The mean
      (SD) total clearance of methohexitone was 16.3 (4.2) ml min-1 kg-1, which is
      greater than that for volunteers or normal surgical patients. The unbound
      clearance correlated positively with body temperature during the infusion (r =
      0.796, P = 0.017). The terminal half-life of methohexitone was 6.3 (3.8) h and
      that of the 4'-hydroxy metabolite 5.8 (2.1) h. There were no marked haemodynamic
      effects of the infusion, and no excessive sedation after the infusion. However,
      the clearance of methohexitone was high and variable, possibly as a direct effect
      of postoperative fever. Consequently, the need for individual titration of the
      rate of infusion is emphasized.

PMID- 1997060
TI  - Propofol as an i.v. anaesthetic induction agent in variegate porphyria.
AB  - The choice of an i.v. anaesthetic induction poses problems for the anaesthetist
      confronted with a patient with one of the acute porphyrias. We undertook a
      prospective clinical trial in 13 variegate porphyric subjects using propofol as
      an anaesthetic induction agent. Urinary porphyrin precursors and porphyrins were
      measured before operation and 1-5 days after operation. Stool and plasma
      porphyrin concentrations were measured over the same period. Comparison of these
      data in the porphyric patients and in 21 control subjects over the trial period
      revealed no significant change in porphyrin or porphyrin precursor output after
      operation. Urinary porphyrin precursor concentrations did not exceed the limits
      established for variegate porphyric patients in remission, and there were no
      changes in the stool and plasma porphyrin profiles or any symptoms of an acute
      porphyric attack. We conclude that propofol did not appear to be porphyrinogenic
      when used for the induction of anaesthesia in 13 patients with variegate
      porphyria.

PMID- 1997061
TI  - Effect of i.v. anaesthesia with propofol on drug distribution and metabolism in
      the dog.
AB  - We have studied the effect of i.v. anaesthesia with propofol in the emulsion
      (Intralipid) formulation on drug distribution and metabolism in six dogs using
      dual-route administration of propranolol as a model compound. Each dog was
      studied on two consecutive days: day 1 awake and day 2 during propofol
      anaesthesia (6 mg kg-1 followed by an infusion of 0.8 mg kg-1 min-1). Propofol
      anaesthesia was associated with reduced intrinsic clearance by 40% (P less than
      0.05) but no significant difference in systemic clearance or hepatic plasma flow.
      Propofol produced marked changes in drug distribution; volume of distribution
      (Vss) of propranolol increased 54% from 82.5 (SEM 7.3) litre awake to 127.3 (27)
      litre during propofol anaesthesia (P less than 0.05). This change was accompanied
      by an increase (P less than 0.05) in the free fraction of propranolol from 8.5
      (0.7) % in awake to 14.0 (0.7) % in propofol-anaesthetized dogs. The combination
      of the effects of both drug clearance and protein binding resulted in a 65%
      decrease in the intrinsic clearance of unbound drug (P less than 0.05). In
      contrast with the effects of propofol on drug distribution, infusion of
      Intralipid alone in another group of six dogs had no significant effects on drug
      distribution, protein binding or drug metabolism. We conclude that propofol is a
      modest inhibitor of drug metabolism, but has major effects on propranolol
      distribution, possibly by changing plasma protein binding.

PMID- 1997062
TI  - Priming of cardiopulmonary bypass with human albumin or Ringer lactate: effect on
      colloid osmotic pressure and extravascular lung water.
AB  - We have undertaken a randomized study on 20 patients undergoing coronary artery
      bypass surgery in order to determine the influence of cardiopulmonary pump prime
      solutions on colloid osmotic pressure and extravascular lung water. Crystalloid
      priming with Ringer lactate was compared with an albumin solution of nearly
      physiological colloid osmotic composition (4%). Measurements of extravascular
      lung water were performed by a modified, highly sensitive thermal dye technique,
      with additional detection of tracer signals in the pulmonary artery. In the
      Ringer lactate group, a significantly greater decrease in colloid osmotic
      pressure occurred immediately after onset of cardiopulmonary bypass. The more
      pronounced decrease in colloid osmotic pressure and in transcapillary gradient
      (difference between colloid osmotic pressure and pulmonary capillary wedge
      pressure) in the Ringer lactate group was associated with a significant increase
      in extravascular lung water (by 60%) in the postoperative period; the human
      albumin group, however, showed only a slight tendency to increased lung water.
      There were no differences in haemodynamic or respiratory states after operation.

PMID- 1997063
TI  - Antithrombotic efficacy of continuous extradural analgesia after knee
      replacement.
AB  - We have studied the effect of extradural analgesia on postoperative venous
      thrombosis in patients undergoing knee arthroplasty. Forty-eight patients were
      allocated randomly to receive either general anaesthesia or extradural analgesia
      with local anaesthetics for 3 days. All patients wore compressive elastic
      stockings and no anticoagulant drugs were administered. Bilateral venography was
      performed 10 days after surgery. Continuous extradural analgesia did not impede
      mobilization of the patients. One case of nonfatal pulmonary embolism occurred in
      a patient who received general anaesthesia. The use of continuous extradural
      analgesia resulted in a significant difference in the total incidence of deep
      vein thrombosis (18% compared with 59% after general anaesthesia (P = 0.02]. The
      incidence of calf vein thrombosis was 12% compared with 45% after general
      anaesthesia (P = 0.05).

PMID- 1997064
TI  - Sensory information processing during general anaesthesia: effect of isoflurane
      on auditory evoked neuronal oscillations.
AB  - There is evidence from neuropsychological and psychophysical measurements that
      sensory information is processed in discrete time segments. The segmentation
      process may be described as neuronal oscillation at a frequency of 30-40 Hz.
      Stimulus-induced neuronal oscillations of this frequency are found in the middle
      latency range of the auditory evoked potential (AEP). We have studied the effect
      of different end-tidal concentrations of isoflurane on auditory evoked 30-40 Hz
      neuronal oscillations. We studied 13 patients undergoing intra-abdominal
      urological and gynaecological procedures. AEP were recorded in the awake state
      and during end-expiratory steady state isoflurane concentrations of 0.3, 0.6 and
      1.2 vol%. These incremental doses of isoflurane caused a stepwise decrease in
      frequency of oscillations. The decrease in oscillation frequency and sometimes
      the disappearance of oscillatory components may be interpreted as suppression of
      sensory information processing. The measurement of auditory evoked neuronal
      oscillations in the AEP appears to be a promising tool to monitor both sensory
      information processing capacity and depth of anaesthesia.

PMID- 1997065
TI  - Barbiturate alteration of respiratory rhythm and drive in isolated brainstem
      spinal cord of newborn rat: studies at normal and hyperbaric pressure.
AB  - High pressure and anaesthetic agents are mutual antagonists in intact animals,
      but antagonism is not observed in isolated nerve cells. In order to test the
      hypothesis that a neural network might display pressure-anaesthetic antagonism
      not found in simpler systems, we have examined the effects of pentobarbitone at
      normal pressure and at 10.1 MPa helium pressure on the rhythmic activity of
      medullary respiratory centres of isolated brainstem and spinal cord from 0-3 day
      old rats. Pentobarbitone 5-80 mumol litre-1 depressed the frequency, amplitude
      and area of spontaneous bursts recorded from C5, reduced respiratory drive, and
      altered the response to trigeminal nerve root stimulation. Compression to 10.1
      MPa decreased ventilatory frequency and respiratory drive, and either did not
      interact with or enhanced the depressant effects of pentobarbitone.
      Pentobarbitone and helium pressure altered the response to trigeminal nerve root
      stimulation in the same manner. The results are consistent with additive rather
      than antagonistic effects of pressure and a barbiturate on the determinants of
      output from the respiratory centre-motor neurone pathway. Pressure-anaesthetic
      antagonism may be a property unique to the neural circuitry which underlies awake
      behaviour and pressure-induced seizures, rather than reflecting a fundamental
      molecular-level antagonism.

PMID- 1997067
TI  - Papers from the French Vascular Surgery Society 1990 meeting.

PMID- 1997066
TI  - Endovascular techniques and the vascular surgeon.

PMID- 1997068
TI  - Interventional therapy: an alternative view.

PMID- 1997069
TI  - Aortic anastomosis in aortobifemoral bypass.

PMID- 1997070
TI  - Long-term results of thrombectomy for late occlusions of aortofemoral bypass.
AB  - Sixty-two first episodes of aortofemoral (eight patients) or aortobifemoral (42
      patients) bypass thrombosis were operated upon in 50 patients between 1980 and
      1985. There were 47 men and three women whose mean age was 58 years. Retrograde
      thrombectomy through the distal anastomosis was achieved in all cases by using
      either a balloon catheter or Vollmar rings. If thrombectomy was impossible,
      revascularization was ensured by an extraanatomic bypass or complete replacement
      of the graft. Angioplasty, repeat distal anastomosis or femoropopliteal bypass of
      the native runoff artery were done in 55 (89%) operations. The cause of
      thrombosis was elucidated in 45 cases. Suture line stenosis and atheromatous
      stenosis of the native runoff artery were the two most common causes. Three
      patients died and two required above-knee amputation in the immediate
      postoperative period. Contralateral embolism occurred in two patients undergoing
      retrograde thrombectomy. Mean follow-up was 47 months. Thrombectomy was possible
      in 51 or 62 prosthetic thromboses (Group I). Thirty-nine of these grafts have
      remained patent. Twelve instances of repeat thrombosis occurred, requiring either
      repeat thrombectomy or a new bypass. Primary patency in group I was 97.8%, 81.2%,
      and 71.3% at one, three, and five years, respectively. Thrombectomy was
      impossible in 11 graft thromboses (Group II). A new bypass was performed in all
      11 cases. Primary patency in Group II was 100%, 75% and 50% at one, three, and
      five years, respectively. Retrograde thrombectomy combined with treatment of
      native runoff artery anomalies can restore long-term patency when thrombosis
      occurs late after aortofemoral bypass and is associated with low mortality and
      morbidity.

PMID- 1997071
TI  - Pre- and intraoperative transcranial Doppler: prediction and surveillance of
      tolerance to carotid clamping.
AB  - We report 91 patients (mean age 70 years) operated upon, prospectively for a
      total of 100 carotid revascularizations (nine bilateral). Eighty-five of these
      patients had pre-, intra-, and postoperative transcranial Doppler investigations.
      Preoperatively, these 85 patients (92 procedures) were classified into two groups
      based on the results of their Doppler examinations: Group A (65 patients, 72
      procedures), those who did not require an intraoperative indwelling shunt and
      Group B (20 patients, 20 procedures), those who did. The shunt was inserted only
      when the mean stump (back) pressure was less than 50 mmHg after cross-clamping.
      Group A all had satisfactory collaterality with a functional anterior and one or
      two posterior communicating arteries. Group B had no communicating arteries
      (anterior or posterior) identified by transcranial Doppler. In 17 of 20 patients
      in this group, the stump pressure was less than 50 mmHg and a shunt was placed.
      The overall prediction based on Doppler examination of whether or not patients
      would need a shunt during operation for the two groups A and B (i.e., 92
      procedures) was correct in 95.6% (88/92) of cases. Moreover, six hemodynamically
      significant stenoses (four in the cavernous portion, two in the middle cerebral
      artery) were disclosed. Sensitivity and specificity of transcranial Doppler as
      correlated with arteriographic findings were 70 and 90%. Preoperative
      transcranial Doppler can measure the velocities of the principal cerebral
      arteries and the collateral capacity of the circle of Willis, and can forecast
      tolerance to carotid cross-clamping. Intraoperatively, the velocity of flow in
      the middle carotid artery was correlated with stump pressure, which allowed for
      surveillance of the shunt.

PMID- 1997072
TI  - Aortoiliac surgery and kidney transplantation.
AB  - Between January 1980 and December 1989, we performed 407 renal transplantations.
      Twelve of these patients (3%) underwent aortoiliac reconstruction before (Group
      I, two patients), concomitant to (Group II, five patients) or after (Group III,
      five patients) renal transplantation. The aortoiliac lesions treated included
      four aneurysms and seven occlusions of the abdominal aorta and one
      postarteriography dissection of the iliac artery. A prosthetic graft was inserted
      in nine cases (75%). Endarterectomy was performed in the three other cases (25%).
      Four of five patients in Group III were operated on without any particular
      protection for the transplant. There were no postoperative deaths in Groups I and
      III. In Group II, one patient died of infection secondary to a urinary tract
      fistula. Early and late vascular morbidity (renal artery stenosis, occlusion of
      aortoiliac reconstruction, anastomotic false aneurysm) occurred with equal
      frequency in the three groups. Renal transplantation in patients having already
      undergone aortoiliac surgery and, conversely, aortoiliac reconstruction in the
      renal transplant patient, are possible without any particular technical
      precautions with minimal mortality and kidney morbidity. Simultaneous renal
      transplantation and aortoiliac reconstruction carries a significant risk of
      infection and a two-stage procedure should be considered in this situation.

PMID- 1997073
TI  - Secondary aortoduodenal fistulas: value of initial axillofemoral bypass.
AB  - Between January 1970 and April 1989, 20 patients underwent operation for
      secondary aortoduodenal fistulas. When the preoperative diagnosis was certain and
      emergency control of bleeding not required, initial axillofemoral bypass was
      performed before ablation of the infected aortic prosthetic graft during the same
      operation. When diagnosis was uncertain or severity of bleeding required
      emergency laparotomy, the therapeutic plan varied over time. Until 1980, we
      performed either a direct repair (three cases) or the ablation of the aortic
      graft followed by secondary axillofemoral bypass (four cases). After 1980, the
      order of procedures was 1) control of bleeding whenever necessary, 2)
      axillofemoral bypass, and 3) ablation of the aortic graft. Postoperative
      mortality was two of 13 in patients undergoing initial axillofemoral bypass,
      compared with six of seven patients undergoing direct surgery or initial ablation
      of the aortic graft. Of the 12 patients surviving the postoperative period, three
      died of aortic stump hemorrhage, four, 12, and 14 months after operation. Two
      patients had a new aortic graft inserted. Repeat replacement of the abdominal
      aorta graft was performed in one case and ascending thoracic aortobifemoral
      bypass in the other because of secondary thrombosis of the axillofemoral bypass.
      We conclude that initial axillofemoral bypass before dealing with the aortic
      graft improves the immediate prognosis in operations for secondary aortoduodenal
      fistulas. This procedure does not, however, preclude the possibility of aortic
      stump infection which can lead to recurrent aortoduodenal fistula. The risk of
      infection or secondary occlusion of axillofemoral bypass is minimal. Secondary
      prosthetic replacement is not systematically necessary.

PMID- 1997074
TI  - Innominate artery involvement in type IV Ehlers-Danlos syndrome.
AB  - We report two cases of innominate artery involvement in patients with Ehlers
      Danlos syndrome. In the first patient, spontaneous dissection of the innominate
      artery was treated successfully. In the other, the patient died of spontaneous
      rupture of the innominate artery in the early postoperative course after
      operation for aneurysm of the celiac artery. Arterial complications occurring in
      Ehlers-Danlos syndrome are rare but pose difficult diagnostic and therapeutic
      problems for the vascular surgeon due to arterial wall fragility.

PMID- 1997075
TI  - Femorofemoral crossover bypass for noninfective complications of aortoiliac
      surgery.
AB  - Between 1973 and 1989, 39 femorofemoral crossover bypasses were performed to
      treat unilateral noninfective complications of aortoiliac surgery. The initial
      revascularization procedure, performed an average of 79.5 months previously, was
      an aortobifemoral bypass in 29 cases, an aorto- or iliofemoral bypass in six
      cases, an inlay graft for abdominal aortic aneurysm and aortoiliac endarterectomy
      in two cases each. The indications for femorofemoral crossover bypass included
      prosthetic occlusion in 35 cases, thrombosed false aneurysm in two, and further
      degradation after endarterectomy (iliac stenosis and occlusion in one case each).
      There was no operative mortality. One patient with acute ischemia upon admission
      and another with distal gangrene required below-knee and forefoot amputations,
      respectively. No amputations were required during the rest of the follow-up
      period. Three repeat aortobifemoral bypasses were performed because of occurrence
      of aortic or inflow vessel lesions. Primary and secondary actuarial five year
      patency rates for femorofemoral crossover bypasses were 59.7% and 78.4%,
      respectively. Femorofemoral crossover bypass can extend the benefits derived from
      direct aortoiliac surgery with low mortality and morbidity in the absence of
      associated aortic pathology (false aneurysm at the aortic implantation site or
      severe obstructive lesions).

PMID- 1997076
TI  - Carotid endarterectomy plaques: correlations of clinical and anatomic findings.
AB  - To establish possible relationships between the structure of carotid plaque and
      neurologic symptoms, 187 consecutive endarterectomy specimens were studied
      prospectively. Each specimen was examined for gross and histopathological
      features. Intraplaque hemorrhage, although found infrequently, was closely
      correlated with the presence of symptoms. Plaque ulcerations were encountered
      more often when lesions were symptomatic. Calcifications were more frequently
      associated with asymptomatic lesions. Consistency of plaque was related to its
      morphological features (stenosis or ulceration) and symptoms. Soft plaques with
      predominant atheromatous grumous material and hemorrhage were associated more
      often with tightly stenotic, ulcerated, and symptomatic lesions. Consistency of
      atherosclerotic carotid plaques should be assessed and considered as an important
      element in the therapeutic decision.

PMID- 1997077
TI  - Surgical reconstruction of the internal carotid artery with contralateral
      occlusion without use of shunt.
AB  - Between 1979 and 1989, 133 carotid artery reconstructions were performed in 130
      patients with contralateral internal carotid artery occlusion. These 133
      reconstructions represent 7.3% of 1815 revascularizations of the internal carotid
      artery for atheromatous lesions performed during the same period. There were 113
      men (87%) and 17 women (13%) whose mean age was 64.8 years (range 38 to 83
      years). Forty-two patients (32%) had coronary artery disease and 77 (59%) were
      hypertensive. Nineteen patients (14%) were asymptomatic; 16 (12%) had symptoms of
      isolated vertebrobasilar insufficiency; 19 (14%) had ipsilateral carotid symptoms
      (on the side of operation); 67 (51%) had contralateral symptoms (on the side of
      occlusion); and 12 (9%) had bilateral carotid symptoms. All procedures were
      performed under general anesthesia without the use of a shunt. Nine patients
      (6.8%) died in the postoperative period (eight of neurologic and one of
      respiratory causes). Twelve patients (9%) sustained a cerebral vascular accident
      (eight ipsilateral and four contralateral). Four of these cerebral vascular
      accidents were diagnosed upon awakening, the remaining eight occurred after an
      initial uneventful recovery. Combined neurologic mortality and morbidity was
      9.8%. Patients with occlusive lesions of the contralateral carotid artery
      undergoing internal carotid artery reconstruction are at high risk for
      postoperative cerebral vascular accidents. It is in this group of patients that
      the various methods of monitoring and cerebral protection should be evaluated.

PMID- 1997078
TI  - Vertebral artery reconstruction: results in 106 patients.
AB  - Between January 1982 and December 1989, we performed 109 revascularizations of
      the vertebral artery in 106 patients. Eighty-six patients (81%) had isolated
      vertebrobasilar insufficiency, 18 (17%) had associated carotid and
      vertebrobasilar pathology while two (2%) had isolated carotid symptoms. The
      procedures performed included 98 revascularizations of the proximal vertebral
      artery and 11 reconstructions of the distal vertebral artery. One distal
      revascularization was required after early failure of proximal revascularization.
      In 36 cases (34%), a concomitant ipsilateral carotid artery revascularization
      procedure was performed, and in one case, an ipsilateral subclavian artery
      aneurysm was excised. Two patients (1.9%) died postoperatively and five patients
      (4.7%) had nonfatal neurologic complications. Four of these seven complications
      occurred after combined vertebral and carotid surgery. One hundred early follow
      up arteriograms were obtained (92% of reconstructions). There were four
      occlusions, two of which were associated with neurologic deficits. Three patients
      were lost to follow-up. Mean follow-up was 48 months (4-100 months). Seven
      patients died in the late follow-up period (after one month). Actuarial five year
      survival was 91%. Overall patency at five years was 96%. The study of late
      neurologic events showed that 63% of patients had complete recovery, 30%
      improvement, and 7%, failure or aggravation of symptoms.

PMID- 1997079
TI  - Pentoxifylline in the nonoperative management of intermittent claudication.
AB  - To assess the clinical effectiveness of pentoxifylline (Trental) in the treatment
      of intermittent claudication and ischemic rest pain, 129 patients were
      retrospectively interviewed with respect to compliance and improvement of
      symptoms. Risk factors for the development of atherosclerosis were tabulated, as
      was the severity of symptomatic lower extremity peripheral vascular
      insufficiency. The duration of pentoxifylline treatment was 35.8 +/- 45.0 weeks
      (mean +/- 1 S.D.). Forty-eight percent of the patients discontinued
      pentoxifylline on their own, most commonly because of side effects (13%) or
      perceived lack of improvement (23%). Of those patients taking pentoxifylline for
      eight weeks or more (n = 110), 64% noted some improvement, with 31% reporting
      increased claudication distance and 52% reduced claudication pain. Pentoxifylline
      provided pain relief in 52% of patients with ischemic rest pain (n = 27). Neither
      diabetes, hypertension, concomitant antiplatelet therapy, the severity of
      claudication, nor pretreatment ankle-brachial Doppler pressures were related to
      treatment outcome. Increased daily walking exercise during treatment was
      associated with successful outcome (p = 0.04). Clinical response to
      pentoxifylline was inversely related to the number of cigarettes smoked daily in
      those with 1 block claudication (n = 71, p = 0.05). Pentoxifylline was not very
      effective in increasing reported claudication distance. This review suggests that
      pentoxifylline may be of value for patients with ischemic rest pain when arterial
      reconstruction is not possible. Whether pentoxifylline is useful adjunctive
      therapy for intermittent claudication requires further scrutiny.

PMID- 1997080
TI  - Vein patch rupture after carotid endarterectomy: a survey of the Western Vascular
      Society members.
AB  - To determine the prevalence, demographics and morbidity of vein patch rupture,
      the authors polled members of the Western Vascular Society. Forty-eight surgeons
      (53% of the members) reported an experience with 23,873 carotid operations. A
      vein patch was used in 1,760 operations (7.4%), and rupture of the patch occurred
      in 13 patients (0.7%), 10 women and three men. Indications for the patch were a
      small artery in 10 patients and restenosis in three. Saphenous vein was used for
      all patches and was harvested from the ankle in 12 patients and from the groin in
      one patient. All ruptures occurred from a split in the vein patch. Hypertension
      was present in seven of the 13 patients. None of the ruptures were associated
      with infection. Two ruptures occurred on the first postoperative day, six on the
      second day, three on the third day, one on the eighth day, and one on the twenty
      first day. Four patients died: airway obstruction (1), hemorrhagic cerebral
      infarction (1), and myocardial infarction (2) were the causes. Three had a stroke
      and survived, one had a retinal embolus, and five underwent reoperation without
      complication. Vein patch of the carotid artery is used infrequently by members of
      the Western Vascular Society. The incidence of rupture of the patch is low
      (0.7%), but when it occurs, there is significant mortality (30.7%), and morbidity
      (30.7%). Patients with a vein patch should be observed in the hospital for three
      days after endarterectomy because rupture demands immediate reoperation.

PMID- 1997081
TI  - Does division of the left renal vein during aortic surgery adversely affect renal
      function?
AB  - Between July 1980 and July 1988, 478 consecutive patients underwent aortic
      aneurysm operations at Royal Prince Alfred Hospital. Renal function was assessed
      by measurement of serum creatinine levels. The left renal vein was divided in 28
      (8%) of the 355 patients undergoing elective aneurysm resection. The mean
      immediate postoperative creatinine values were significantly higher after left
      renal vein division, 193 +/- 174 mumol/L, compared to 133 +/- 93 mumol/l for
      those whose left renal vein remained intact (p less than 0.05 by Mann-Whitney U
      test). After one month, serum creatinine levels had decreased but were still
      significantly higher in those patients in whom the left renal vein had been
      divided, 170 +/- 166 mumol/l, compared to those in whom it was left intact 109 +/
      49 mumol/l (p less than 0.05 by Mann-Whitney U test). The suprarenal aorta was
      cross-clamped in seven (25%) of the 28 patients in whom the left renal vein was
      divided, compared to 21 (6%) of the 327 with the left renal vein intact. A rise
      in creatinine level was observed after suprarenal aortic cross-clamping. The left
      renal vein was divided in 17 (14%) of the 123 patients having emergency surgery
      for ruptured aortic aneurysm, 61 (49%) of whom survived more than 30 days. The
      mean immediate postoperative creatinine values were significantly higher after
      left renal vein division, 426 +/- 277 mumol/l, compared to those in whom the vein
      was left intact, 178 +/- 136 mumol/l (p less than 0.05 by Mann-Whitney U test).
      After one month, serum creatinine levels were still significantly higher in those
      patients in whom the left renal vein had been divided. Although division of the
      left renal vein is a useful way to improve exposure of the juxtarenal aorta, the
      maneuver is associated with an adverse effect on renal function.

PMID- 1997082
TI  - Descending thoracic aorta as an inflow source for late occlusive failures
      following aortoiliac reconstruction.
AB  - From November 1984 to March 1990, 10 descending thoracic aorta-to-femoral artery
      bypass procedures were performed after failure of one or several aortoiliofemoral
      reconstructions. All patients were men, mean age 60 years. Indications included
      noninfected false aneurysm of an infrarenal end-to-side aortoprosthetic
      anastomosis in one case; one occlusion of an axillofemoral bypass; degradation of
      an aortobifemoral prosthetic graft; two occlusions of aortofemoral bypass; and
      five occlusions of aortobiliac or aortobifemoral bypasses. Eight bifurcated
      grafts, one aortoprosthetic tube graft, and one aortopopliteal tube graft were
      inserted. One patient died 23 days postoperatively of multiple organ failure.
      Three patients underwent a successful seconary lower limb reconstruction
      procedure (prosthetic limb thrombectomy, embolectomy, femoral bifurcation
      angioplasty in one case each). Mean survival time was 14 months (range 3-48
      months). Two patients were lost to follow-up, and one died of myocardial
      infarction six months postoperatively with a patent bypass. Graft thrombosis
      occurred in two patients. One was treated by thrombectomy at five months, the
      other was treated by in-situ thrombolysis at 15 months. Both of these patients
      had patent grafts at 12 and 21 months, respectively. The four other patients had
      patent grafts at 48 months. Primary patency was 55.5% (5/9 survivors) and
      secondary patency was 100% (9/9). This is a relatively simple method for
      constructing an extraanatomic aortofemoral or aortobifemoral bypass in late
      failures of aortoiliofemoral reconstructive surgery without having to re-enter
      the abdomen.

PMID- 1997083
TI  - Wound instillation for postoperative pain relief: a comparison between
      bupivacaine and saline in patients undergoing aortic surgery.
AB  - In a double blind trial 72 patients having elective aortic surgery were
      randomized to receive either 40 ml of 0.25% bupivacaine or 40 ml of saline
      through one or two indwelling wound irrigation catheters every four hours over a
      total of 48 hours. In transverse incisions the two catheters were randomly placed
      either subcutaneously or in the rectus sheath; in vertical incisions one catheter
      was placed subcutaneously. Analgesia was assessed by visual analogue score on
      Postoperative Days 1 and 2 and the number of doses of intramuscular morphine
      given during the instillation period. Pulmonary function was monitored by forced
      expiratory volume and peak flow on Postoperative Days 1 to 5; arterial blood
      gases were monitored preoperatively and Postoperative Day 2. In all parameters
      evaluated there was no statistically significant difference between the saline (n
      = 33) or the bupivacaine (n = 37) groups. Site of the catheter in the transverse
      groups made no difference. Comparing vertical (n = 21) and transverse (n = 49)
      incisions, the mean visual analogue scores on the first postoperative day were 40
      and 29, respectively (p less than 0.05). Wound instillation with bupivacaine
      neither improves pulmonary function nor reduces morphine requirements when
      compared to saline. Transverse incisions may be less painful than vertical ones.

PMID- 1997084
TI  - Upper limb embolus: a timely diagnosis.
AB  - In a ten year period, 36 patients were treated surgically for embolic occlusion
      of upper limb vessels. The sources of embolus were cardiac (58%), peripheral
      aneurysm (22%) and unknown (20%). Brachial embolectomy was performed in all
      cases. Six out of eight peripheral aneurysms were resected. A patency rate of 94%
      was achieved at five years. Hospital mortality and morbidity rates were 3% and
      10%, respectively. One patient died of a myocardial infarct one week
      postoperatively. Three patients suffered ischemic contracture or amputation; all
      three presented after 36 hours. We conclude that upper limb emboli are usually
      easy to recognize and treat. Prompt surgery (less than 24 hours) produces the
      most satisfactory results. Late presentation or delay in treatment can result in
      limb loss.

PMID- 1997085
TI  - Aortic pseudoaneurysm secondary to celiac plexus block.
AB  - Traumatic pseudoaneurysm of the abdominal aorta has been infrequently reported in
      the literature. We report a case of an infected pseudoaneurysm of the supraceliac
      aorta which we believe to be secondary to celiac plexus block performed for pain
      from chronic pancreatitis. The aneurysm was successfully repaired using a Dacron
      graft through a thoracoabdominal approach. The possible mechanism of aortic
      injury from celiac plexus block is discussed.

PMID- 1997086
TI  - True profunda femoris aneurysms: are they more dangerous than other
      atherosclerotic aneurysms of the femoropopliteal segment?
AB  - Three cases of true aneurysms of the profunda femoris artery are reported along
      with a review of 17 other cases in the literature. These aneurysms are rare and
      commonly present with rapid enlargement or rupture (9/20), the risk of rupture
      being higher than those affecting the femoral or popliteal arteries. All patients
      underwent successful surgical treatment except for one who required amputation.
      The diagnosis of an aneurysm of the profunda femoris artery must be considered in
      all patients with a pulsatile swelling in the groin. Surgical treatment is
      mandatory, and it carries a low mortality as well as a low risk of amputation.

PMID- 1997087
TI  - Basic data related to clinical decision-making in acute limb ischemia.

PMID- 1997088
TI  - Deficiencies of the modern vascular surgeon: a dilemma, a solution.

PMID- 1997089
TI  - Acquired immunodeficiency syndrome (AIDS)--data as at 31 December 1990.

PMID- 1997090
TI  - Expanded programme on immunization. Global Advisory Group--Part 1.

PMID- 1997091
TI  - The process of peer-review.

PMID- 1997092
TI  - Prosthetic replacement surgery for bone tumours--cure at less cost?

PMID- 1997093
TI  - Familial renal cell carcinoma: clinical and molecular genetic aspects.
AB  - Renal cell carcinoma (RCC) accounts for 2% of all human cancer, but familial
      cases are infrequent. Riches (1963) and Griffin et al. (1984) in a population
      based case-control study found a family history of renal cell carcinoma in 2.4%
      of affected patients compared to 1.4% of controls. Nevertheless the importance of
      inherited tumours in clinical practice and medical research is disproportionate
      to their frequency. In clinical practice recognition of familial RCC can provide
      opportunities to prevent morbidity and mortality by appropriate screening. In
      medical research recent advances in molecular genetics offer the prospect of
      isolating the genes involved in the pathogenesis of familial RCC and of the more
      common sporadic cases. In this article we review the clinical and molecular
      genetics of inherited renal cell carcinoma (adenocarcinoma or hypernephroma).

PMID- 1997094
TI  - Mutations in p53 do not account for heritable breast cancer: a study in five
      affected families.

PMID- 1997095
TI  - The killing effect of 4-S-cysteaminylphenol, a newly synthesised melanin
      precursor, on B16 melanoma cell lines.
AB  - We have examined the killing effect of 4-S-cysteaminylphenol (4-S-CAP), a newly
      synthesised melanin precursor, on B16 melanoma cell lines possessing different
      melanin-producing activities and found it to be particularly effective in heavily
      melanised melanoma cells, but less so in moderately melanised melanoma cells, and
      having no effect on amelanotic melanoma cells and nonmelanoma cells. Thus, it was
      found that the killing effect of 4-S-CAP is highly dependent upon the synthesis
      of melanin and tyrosinase in melanoma cells, suggesting that 4-S-CAP may become
      toxic to melanoma cells only after oxidation by tyrosinase. The killing activity
      of 4-S-CAP also was found to be associated with a profound inhibition of the
      thymidine incorporation in pigmented melanoma cells, as compared to the uridine
      and leucine incorporation. Further, the inhibition of DNA synthesis was most
      pronounced in heavily melanised melanoma cells, less so in moderately melanised
      melanoma cells, and not seen in amelanotic melanoma cells. As a possible
      mechanism that might account for this action, it may be that 4-S-CAP is oxidised
      by tyrosinase to the o-quinone form via the catechol derivative and that some of
      the quinones then conjugate with sulfhydryl enzymes including DNA polymerase,
      thus exerting a killing activity for pigmented melanoma cells. Thus, 4-S-CAP
      appears to provide a new, effective cytotoxic agent for rational chemotherapy of
      malignant melanomas.

PMID- 1997096
TI  - Formation of interaction products of carboplatin with DNA in vitro and in cancer
      patients.
AB  - Binding of the cytostatic drug carboplatin to DNA was studied in solution, in RIF
      1 and CHO cell lines and in human buccal cells after in vitro or in situ drug
      exposure. Results were compared with DNA adduction by cisplatin. The rate of
      binding in solution, determined by atomic absorption spectroscopy, was 35 times
      lower for carboplatin than for cisplatin. Adduct formation in cells in vitro was
      determined in a quantitative immunostaining assay. Staining intensities after
      carboplatin treatment were at least 29 times lower than after an equimolar dose
      of cisplatin. For RIF-1 and CHO cells, maximum levels of carboplatin-induced DNA
      modification were obtained 24 h after treatment; these levels correlated with
      cell killing. Adduct-specific staining in buccal cells from two carboplatin
      treated patients increased 5-7 fold between 0 and 14 h after infusion, reaching a
      maximum at 10-14 h. This strongly contrasts with buccal cells from a cisplatin
      treated patient, in which the adduct-specific staining signal increased by only
      23% between 0 and 6 h after infusion, and then declined. This difference in the
      rate of adduct formation in vivo is consistent with the in vitro data.

PMID- 1997097
TI  - Reversibility of the malignant phenotype in monoclonal tumours in the mouse.
AB  - Longterm goitrogen administration to rodents is well known to result in multiple
      proliferative lesions of the thyroid. The regression of these lesions on
      withdrawal of goitrogen has led to their neoplastic nature being questioned, and
      they have been regarded as 'nodules' rather than as true tumours. We have induced
      multiple thyroid lesions by the combined use of high dose radiation as a mutagen,
      together with goitrogen administration to induce prolonged TSH growth
      stimulation. G6PD histochemistry was used in heterozygous G6PD deficient female
      mice to show that all the thyroid lesions induced by this regime were
      monophenotypic, and therefore monoclonal in origin. The great majority of induced
      tumours were adenomas, a minority were carcinomas. The number of carcinomas
      observed was significantly lower in a group of animals from which goitrogen was
      withdrawn for 4 weeks prior to killing, when compared to animals killed while on
      goitrogen treatment. Both adenomas and carcinomas, including areas of
      intravascular tumour, showed morphological features of regression on withdrawal
      of the goitrogen. There are three key cellular changes which must occur in
      spontaneous thyroid carcinogenesis--escape from a growth limiting mechanism,
      acquisition of TSH independent growth and acquisition of invasiveness. In the
      natural selection of mutations or epimutations during carcinogenesis, prolonged
      high levels of TSH are likely to remove any selective advantage from mutations
      that lead to TSH independent growth. Tumours induced by a regime including
      prolonged goitrogen treatment may therefore develop following two rather than
      three key stages. They will occur with an increased frequency relative to lesions
      observed in spontaneous carcinogenesis, but will retain TSH dependency. We
      speculate that several mechanisms may lead to loss of the growth limiting
      mechanism, including translocation of an oncogene to the region of a TSH induced
      promoter. Other carcinogenic regimes may also increase the yield of tumours by
      creating conditions which reduce the number of essential steps required for
      carcinogenesis, and may involve translocation to a carcinogen inducible promoter.

PMID- 1997098
TI  - Prediction of tumour sensitivity to 4-hydroperoxycyclophosphamide by a
      glutathione-targeted assay.
AB  - In an attempt to develop an assay to predict patient tumour response to
      cyclophosphamide (CP), the feasibility of using a glutathione-targeted assay to
      assess the in vitro chemosensitivity of tumour cells to 4
      hydroperoxycyclophosphamide (4-OOH-CP), an activated congener of CP, was
      evaluated. A panel of 19 human and three murine tumour cell lines was used. These
      consisted of three main categories of tumour types, viz. ovarian, lung and
      squamous cell carcinoma. The major finding was that the occurrence of a
      significant reduction of tumour cell reproductive capacity was always accompanied
      by substantial depletion of cellular glutathione (GSH) content, and vice versa.
      Plots of % GSH depletion versus clonogenic cell survival demonstrated highly
      significant correlation (r = 0.90-0.91; P less than 0.01). It was determined that
      for in vitro tumour cell lines, a GSH depletion to 40% of initial content may
      serve as a cut-off criterion for chemosensitivity to 4-OOH-CP. This degree of GSH
      depletion is indicative of clonogenic cell survival of approximately 1% (95%
      confidence limits = 3 x 10(-5)-1.6 x 10(-2)). The relationship between steady
      state GSH content and intrinsic sensitivity to 4-OOH-CP was also evaluated. The
      GSH concentration of the tumour cell lines ranged from 1.3-21.2 x 10(-18) moles
      microns-3; chemosensitivity to 4-OOH-CP, in terms of IC99, was in the range of
      5.0-87.1 microM. A good correlation was observed between these two parameters (r
      = 0.85, P less than 0.02). These results suggest that GSH plays an important role
      in determining the therapeutic efficacy of 4-OOH-CP in the treatment of cancer.
      It is uncertain, however, whether a high tumour steady state GSH content in
      itself is sufficient to cause therapeutic failure in patients.

PMID- 1997099
TI  - The effects of intracolonic EGF on mucosal growth and experimental
      carcinogenesis.
AB  - Although intra-luminal epidermal growth factor (EGF) may stimulate cell
      proliferation in the upper gastrointestinal tract, its role in the large bowel
      has not been established. We have therefore studied the effect of intra-rectal
      EGF administration on both normal growth and carcinogenesis in the rat colon.
      Colonic cancer was induced in rats with azoxymethane (10 mg kg-1 week-1 for 12
      weeks s.c.) and controls dosed with saline. In each group, animals were
      randomised to receive EGF (12 nM, 0.8 nM or saline control) in 0.5 ml saline via
      a rectal tube daily for 24 weeks. At this time, crypt cell production rates
      (CCPRs) were determined at two sites in the colon: one of maximal and another of
      minimal exposure to EGF (5 cm and 10 cm from the anal margin respectively). No
      effects of EGF were seen at 10 cm. The lower dose of EGF gave CCPRs that mirrored
      the control values. The higher dose of EGF in the animals not treated with
      azoxymethane stimulated mucosal growth. Azoxymethane increased in CCPR, but this
      was suppressed by the high dose of EGF. These results suggest that (1) luminal
      EGF and azoxymethane independently increase the colonic CCPR and their combined
      effect is not synergistic but antagonistic; (2) EGF may have a role in normal
      epithelial growth, but does not potentiate colonic carcinogenesis in this model.

PMID- 1997100
TI  - Resistance to anticancer drugs in NIH3T3 cells transfected with c-myc and/or c-H
      ras genes.
AB  - NIH3T3 cells transfected with c-H-ras and/or c-myc genes were examined for
      differences in drug sensitivity. The five transfectants used were N8, NIH3T3-nm
      1, pT22-3-nm-2, pP1-4 and pT22-3. They were transfected with pKOneo alone, pKOneo
      and c-myc, pKOneo and c-myc plus activated c-H-ras, normal c-H-ras and activated
      c-H-ras genes, respectively. The IC50s of cisplatin, 4
      hydroperoxycyclophosphamide, adriamycin, melphalan, and CPT-11 were significantly
      higher for NIH3T3-nm-1 abd pT22-3-nm-2 than for the parental NIH3T3 and N8 cells.
      Transfection with normal and activated C-H-ras oncogenes only led to increases in
      the IC50s of alkylating agents. There was no significant difference between the
      IC50s of N8 and those of NIH3T3 parental cells to any of these anticancer agents.
      These results strongly suggest that the expression of the c-myc gene plays a role
      in the acquisition of drug resistance. The c-myc gene may therefore provide us
      with an important clue in determining the mechanism of drug resistance.

PMID- 1997101
TI  - Photodynamic therapy of a mouse glioma: intracranial tumours are resistant while
      subcutaneous tumours are sensitive.
AB  - Subcutaneous and intracranial VMDk tumours were treated with photodynamic therapy
      (PDT) using a new sensitiser, m-THPP. Subcutaneous tumours were highly sensitive
      to PDT but intracranial tumours were much more resistant, requiring a 30-fold
      increase in sensitiser dose to produce equivalent levels of necrosis. Resistance
      of intracerebral tumours was not due to failure of the sensitiser to enter
      tumours. Necrosis of intracranial tumours was increased when mice breathed 100%
      oxygen during PDT while subcutaneous tumour necrosis was unaffected.

PMID- 1997102
TI  - Production of parathyroid hormone-related protein in tumour xenografts in nude
      mice presenting with hypercalcaemia.
AB  - This study examined the pathophysiological role of parathyroid hormone-related
      protein (PTHrP) in humoral hypercalcaemia of malignancy (HHM). Seven human tumour
      xenografts were analysed in nude mice; five tumours (KEsC-2, oesophageal
      carcinoma; FA-6, pancreatic carcinoma; SEKI, melanoma; Lu-65A and Lu-61, lung
      carcinomas) were associated with hypercalcaemia and two tumours (MIA PaCa-2,
      pancreatic carcinoma; PLC/PRF/5, hepatocellular carcinoma) with normocalcaemia.
      Northern blot analyses, radioimmunoassay and bioassay confirmed the synthesis of
      PTHrP-like peptides by all five tumours associated with hypercalcaemia, but not
      by the two associated with normocalcaemia. These observations indicated a very
      close relationship between the production of PTHrP and the development of HHM.
      Gel filtration studies of three tumour tissue extracts revealed at least two
      different molecules with both PTHrP-like immunological and biological activities.
      One peak eluted at a position between PTHrP (1-141) and cytochrome C and the
      other at a position identical to cytochrome C. These results suggest that PTHrP
      molecules with a molecular size equal to or greater than cytochrome C participate
      as causative agents of HHM. All five tumour xenografts caused hypercalcaemia when
      grown to a size of 1.5 g in nude mice. Under cell culture conditions, four
      original cell lines, KEsC-2, FA-6, SEKI and Lu-65A secreted 450.0, 45.0, 3.6 and
      3.0 pmol of immunoreactive PTHrP/1.5 x 10(9) cells (approximately equivalent to
      1.5 g wet weight) 24 h-1 into their respective culture media. Since a
      subcutaneous infusion of 100 pmol 24 h-1 of PTHrP (1-34) into nude mice was
      sufficient to induce significant hypercalcaemia, we speculate that PTHrP alone
      released from tumour cells could induce hypercalcaemia at least in the case of
      KEsC-2, and possibly in FA-6. With regard to other tumours associated with
      hypercalcaemia, further examination of PTHrP and other compounds with bone
      resorbing activity in these transplantable tumours is required to obtain a better
      understanding of this morbidity.

PMID- 1997103
TI  - Evaluation of adjuvant psychological therapy for clinically referred cancer
      patients.
AB  - Adjuvant psychological therapy (APT) is a newly developed cognitive behavioural
      treatment which has been designed specifically to improve the quality of life of
      cancer patients by alleviating emotional distress and inducing a fighting spirit.
      We report a phase I/II study which evaluates APT in routine clinical practice. A
      consecutive series of 44 outpatients with various cancers referred for
      psychiatric consultation and receiving APT at the Royal Marsden Hospital was
      studied. Standardised self-report questionnaires were used to measure anxiety,
      depression and four principal categories of mental adjustment to cancer, namely,
      fighting spirit, helplessness, anxious preoccupation and fatalism. Statistical
      comparisons between pre-therapy scores and scores after an average of five APT
      sessions revealed significant improvement in anxiety, depression, fighting
      spirit, anxious preoccupation and helplessness. Fatalism scores showed the same
      trend, but the changes were smaller. Patients with advanced disease showed as
      much improvement as those with local or locoregional disease. Present results
      indicate improvement in both psychiatric symptoms and mental adjustment to cancer
      associated with APT. Whether this association is causal remains to be determined
      by randomised controlled trials. Such a trial is in progress.

PMID- 1997104
TI  - A proposal for short-term quality control in breast cancer screening.
AB  - Current proposals for a monitoring and evaluation system in breast cancer
      screening programmes focus on mortality reduction. Here emphasis is laid on the
      prevention of too high a number of false-positive screening results, i.e. no
      subsequent demonstration of malignancy. By comparing the specificity of the
      screening test, the positive predictive value and the detection rate with
      reference values, the screening performance can be measured in a very early phase
      of the programme, even before the registration results on interval cancers become
      available. The proposed average reference values for the first screening round
      are 99.2%, 40% and 5.4/1000, respectively. Measures specifically for the age
      groups 45-49, 50-59 and 60-69 will be given, thus allowing improvements to be
      made if necessary.

PMID- 1997105
TI  - Analgesics in cancer pain: current practice and beliefs.
AB  - Prescribing practices for patients with cancer pain among populations of doctors
      in the United Kingdom have been assessed by means of a postal questionnaire. The
      results indicate that amongst the sample of doctors completing the questionnaire
      the basic principles of pain control in cancer appear to be understood. Regular
      oral morphine or diamorphine are most often chosen with the dose being determined
      mainly by the severity of pain with no arbitrary upper limit. Fears of addiction
      and respiratory depression, and a relatively long prognosis no longer appear to
      be major deterrents to the use of strong opioid analgesics. These data indicate
      considerable shifts in opinion in the doctors responding to the questionnaire and
      these results and their implications for current and future teaching about the
      management of cancer pain are discussed.

PMID- 1997106
TI  - The clinical effects of prolonged treatment of patients with advanced cancer with
      low-dose subcutaneous interleukin-2 [corrected].
AB  - Thirty-five patients with advanced malignant disease have been treated as
      outpatients with increasing doses (0.1-100 mcg) of interleukin 2 (IL2) by once
      daily self-administered subcutaneous (s.c.) injection, 5 days weekly for 8 weeks
      followed by a 4 week observation period. Systemic side effects were not
      experienced by patients at the 3 lower doses. Three patients required dose
      reduction from 100 mcg daily because of intolerance (fever, rash, lethargy,
      nausea and vomiting) and one patient was discontinued because of dyspnoea. We
      observed immunological effects at the 100 mcg dose (but not at the lower doses).
      These consisted of (a) a modest sustained lymphocytosis, (b) eosinophilia in six
      (out of nine) patients and (c) a significant rise in IL2-stimulated peripheral
      blood lymphocyte activated killer (LAK) cell activity in six (out of nine)
      patients to a mean of 2.0 times pretreatment levels (P less than 0.01). Two (out
      of nine) patients with renal cell carcinoma treated with 100 mcg daily had
      partial responses of duration 4 and 9 months respectively and a further three had
      disease stabilisation for at least 3 months. Low dose long-term s.c. IL2 is
      clinically and immunologically active, and in comparison to other IL2 regimens it
      has minor toxicity and is easy to administer. These characteristics make low dose
      s.c. IL2 suitable for study in the adjuvant setting.

PMID- 1997107
TI  - Poor prognosis for malignant melanoma in Northern Ireland: a multivariate
      analysis.
AB  - All cases of cutaneous malignant melanoma, CMM, diagnosed in Northern Ireland
      between 1974-1978 were reviewed, classified and followed up until the end of
      1984. The overall 5 year survival is 54%, among the worst reported in recent
      literature. Multivariate analysis of these cases confirms some previous findings
      from other studies, but also reveals features not apparent in univariate
      analysis. Prognosis worsens with increasing thickness and the presence of
      ulceration. Likewise histopathological type has an independent effect on
      survival, ALM having the worst prognosis. Tumour profile emerges as a significant
      feature affecting prognosis, flat lesions having the poorest outlook, given their
      thickness. Survival is worse with increasing age. Anatomical site is less
      important than suggested by previous univariate analysis. Sex has little
      influence on prognosis when adjusted for the other variables. Cell type and
      pigmentation are of no prognostic value. Several features including diagnostic
      delay contribute to the poor overall survival for CMM in Northern Ireland.
      Educational intervention is essential if this trend is to be reversed.

PMID- 1997108
TI  - Clinical and immune modulatory effects of alternative weekly interleukin-2 and
      interferon alfa-2a in patients with advanced renal cell carcinoma and melanoma.
AB  - The clinical and immune modulatory effects of interleukin-2 (IL-2) and interferon
      (INF) alfa-2a were examined in a phase II study in patients with metastatic renal
      cell carcinoma (six patients) and melanoma (eight patients). Treatment consisted
      in IL-2 3 MU/m2 continuous infusion days 1-4 and INF alfa-2a 6 MU/m2
      subcutaneously day 1 and 4, both given on alternate weeks. Tumour response was
      assessed after four cycles of treatment or earlier, if necessary. Patients with
      stable disease or response were to be continued for another nine cycles or up to
      disease progression. The 14 patients received a total of 60 cycles of treatment.
      Major toxicities (WHO Grade III/IV) were fever, capillary leak syndrome with
      hypotension, nausea and vomiting, erythema with pruritus, leuco- and thrombopenia
      and sepsis with staphylococcus aureus. Five of 14 patients (36%) developed a self
      limiting autoimmune thyroiditis with HLA-DR expression on thyrocytes. Long term
      treatment toxicity was moderate with an average weight loss of 5% and an average
      fall in Karnofsky index of 10% compared to baseline. No responses were seen in
      renal cell carcinoma, two patients with melanoma had a partial and two a minor
      response with a duration of 1-7 months. Serial measurements of immune modulatory
      parameters showed a functional response to treatment with an increase of NK- and
      LAK-activity during the first two cycles, followed by a plateau and decrease
      during the third and fourth cycles. These findings were paralleled by a
      successive decline in treatment induced INF gamma response. These findings
      suggest, that alternative weekly treatment with IL-2 and INF alfa-2a results in
      an exhaustion of lytic capacity of NK- and LAK-cells and an attenuation of
      secondary cytokine release.

PMID- 1997109
TI  - DNA flow cytometry of hereditary and sporadic paragangliomas (glomus tumours).
AB  - Paragangliomas (glomus tumours) are benign, hypervascular tumours which in
      general are treated by surgical excision. The indication for treatment of these
      often slow-growing tumours needs additional criteria for predicting tumour
      progressiveness. For this reason the nuclear DNA content of 99 paragangliomas, 65
      of them originating from patients with a positive family history, was analysed by
      flow cytometry. Unequivocal evidence of DNA aneuploidy was found in 37% of these
      clinically and histologically benign tumours, the average duration of follow up
      amounting to at least 10 years. The DNA index of the aneuploid tumours ranged
      from 0.90 to 2.03. No correlation was found between DNA ploidy and familiality or
      between DNA content and clinical criteria indicative of tumour progression, which
      means that DNA ploidy of these tumours cannot serve as a predictor for an
      expected growth pattern or familiality. DNA aneuploidy in hereditary and sporadic
      paragangliomas is not clinically related to malignancy, but indicates that these
      tumours are true neoplasias cytogenetically.

PMID- 1997110
TI  - Critical factors for the reversal of methotrexate cytotoxicity by folinic acid.
AB  - The cytotoxicity of methotrexate (MTX) on representative human tumour cell lines
      (two cell lines from head and neck carcinomas, two from breast carcinomas, two
      from osteosarcomas and one lymphoblastoid cell line) was evaluated to: (1)
      examine the optimal time interval between MTX and folinic acid (FA)
      administration; (2) determine the critical FA/MTX concentration ratios; and (3)
      compare the relative effects of the equimolar mixture d,I-FA and I-FA. The
      cytotoxic effects of MTX were assessed by the MTT semi-automated test. For all of
      the cell lines tested, a significant inverse relationship was noted between the
      degree of MTX cytotoxicity reversal and the duration of the time interval between
      MTX and FA administration. Overall an 18-24 h interval between MTX and FA
      represented a time-threshold after which MTX effects could not efficiently be
      reversed by FA in most cell lines. With shorter time intervals between MTX and
      FA, MTX cytotoxicity could be partially on even totally reversed by FA; the
      intensity of reversal varied among the cell lines tested, and depended on the
      FA/MTX ratio. Regardless of the interval between MTX and FA, analysis of the
      various FA/MTX ratios revealed a significant direct relationship between this
      ratio and the percentage of recovery. Presence of the d-form had no influence on
      the MTX rescue capacity of the I-form; this suggests that the presence of the d
      FA is unlikely to have any significant clinical consequences.

PMID- 1997111
TI  - The use of angiotensin II as a potential method of targeting cytotoxic
      microspheres in patients with intrahepatic tumour.
AB  - Cytotoxic microspheres have been developed for intra-arterial use in patients
      with liver metastases. Following injection, the distribution of microspheres
      reflects the pattern of hepatic arterial blood-flow. Vasoactive agents, such as
      angiotensin II, by producing vasoconstriction in normal liver, might divert
      arterial blood toward tumour and thereby enhance the delivery of drug-loaded
      particles. Using a double isotope technique, the distribution of radiolabelled
      microspheres to tumour and normal liver tissue was measured before and after
      angiotensin II infusion in nine patients with multiple liver metastases. The
      median increase in tumour: normal ratio following angiotensin II infusion was by
      a factor of 2.8 (range 0.8-11.7, P less than 0.05). This novel approach to
      regional chemotherapy, using a combination of angiotensin II infusion and
      cytotoxic microspheres, increases the exposure of tumour to cytotoxic agents and
      may, therefore, enhance tumour response rates.

PMID- 1997112
TI  - Phase II trial of trimelamol in refractory ovarian cancer.
AB  - Trimelamol is an analogue of hexamethymelamine which exhibited activity against
      refractory ovarian cancer in phase I clinical trial. The dose limiting toxicity
      was leukopenia. In a phase II study, 42 patients with recurrent, or platinum
      complex resistant, advanced ovarian cancer were treated using the dose schedule
      800 mg m-2 i.v. daily for 3 days. There were one complete, three partial and five
      minor responses, objective response rate: 9.5%. The main toxicity observed was
      nausea and vomiting, myelosuppression was minor. The role of Trimelamol in the
      treatment of ovarian cancer remains to be defined, but its activity is limited in
      refractory disease.

PMID- 1997113
TI  - Abnormalities of essential fatty acid distribution in the plasma phospholipids of
      patients with bladder cancer.
AB  - We have examined the composition of the essential fatty acids in the plasma
      phospholipid fractions of 98 patients with histologically proven bladder cancer.
      These patients were attending hospital for regular follow-up by check cystoscopy.
      Patients were divided into two groups, depending on the cystoscopic findings, of
      either active (tumour recurrence seen) or inactive (no evidence of tumour
      recurrence) disease. Compared with a normal population, the plasma levels of most
      of the fatty acids, including arachidonic acid, were significantly lower in the
      98 cancer patients (P less than 0.001, t-test). We were unable, however, to
      demonstrate any significant differences (Mann-Whitney U-test) between the active
      and inactive disease groups. Plasma levels of the essential fatty acids are
      abnormal in patients with bladder cancer; they do not help, however, to
      distinguish those patients with active disease from those with inactive disease.
      This may arise because the deficit in essential fatty acids we have demonstrated
      is a predisposing factor for the development of bladder cancer rather than a
      metabolic consequence of the tumour. Further studies are needed to establish the
      possible clinical role of measurement of essential fatty acids in patients with
      bladder carcinoma.

PMID- 1997114
TI  - p53 in colorectal cancer: clinicopathological correlation and prognostic
      significance.
AB  - p53 protein was detected by immunohistochemistry in 42% of 52 colorectal
      adenocarcinomas. Positive tumours were significantly more frequent in the distal
      colon, and demonstrated a higher rate of cell proliferation. No correlation was
      found with tumour grade, Dukes' stage, presence of DNA aneuploidy or patient
      survival. The role of p53 in colorectal carcinogenesis is discussed with
      particular reference to differences between proximal and distal large bowel
      cancers.

PMID- 1997115
TI  - The use of duplex sonography in the detection of colorectal hepatic metastases.
AB  - Conventional imaging techniques are of limited value in identifying small liver
      metastases. Indirect methods of measuring blood-flow have shown that metastases
      may be associated with subtle changes in liver blood-flow. Doppler
      ultrasonography has the ability to measure liver blood-flow directly. In this
      study, the role of duplex sonography in the detection of hepatic metastases was
      evaluated. Hepatic arterial and portal venous blood-flows were measured in 30
      patients awaiting surgery for colorectal cancer and 16 controls. The ratio of
      hepatic arterial: portal venous blood-flow (Doppler flow ratio; DFR) and the
      ratio of hepatic arterial:hepatic arterial and portal venous blood-flow (Doppler
      perfusion index; DPI) were calculated. Clear separation of the DPI and DFR values
      of controls and patients with histologically confirmed liver metastases was
      observed (P less than 0.001). The data suggest that the measurement of liver
      blood-flow by duplex sonography may be of value in the diagnosis of colorectal
      liver metastases.

PMID- 1997116
TI  - Functional glucocorticoid inducible enhancer activity in the 5'-flanking
      sequences of the rat growth hormone gene.
AB  - Glucocorticoid regulation of rat growth hormone (rGH) gene expression has been
      investigated in a series of gene transfer studies into cells in culture. It has
      been established that sequences (-12 to -523) immediately flanking the start site
      for rGH gene transcription behave as a functional glucocorticoid inducible
      enhancer when associated with a heterologous promoter (RSV), displaying
      independence of orientation and position in mediating the glucocorticoid effect.
      The induction of chloramphenicol acetyl transferase (CAT) gene expression in
      these constructs by dexamethasone was established at the enzyme and mRNA levels
      and was inhibited in the presence of the antiglucocorticoid, RU 38486. The
      glucocorticoid inducible enhancer activity was not restricted to pituitary cells.
      The constructs containing the rGH-5'-flanking sequences, associated with the RSV
      promoter, also mediated glucocorticoid induction of CAT gene expression when
      transiently transfected into MH1C1 cells, a hepatoma cell line. The effect was
      similarly demonstrable on co-transfection of these constructs with a
      glucocorticoid receptor expression vector into receptor deficient COS cells. Two
      elements within these rGH sequences (-97 to -111 and -250 to -264) display
      partial homology with a consensus sequence computed for a group of glucocorticoid
      regulatory elements. Mutation of both of these elements or of the more proximal
      element alone (-97/-111) led to a complete loss of ability to mediate
      glucocorticoid induction of gene expression. However, the rGH sequences still
      mediated glucocorticoid induction of gene expression when the distal GRE-like
      element was mutated or deleted. Thus, the proximal rGH GRE-like element is
      absolutely required to mediate this glucocorticoid inducible enhancer activity.

PMID- 1997117
TI  - In vitro studies on steroidogenesis in the presence of pregnenolone as precursors
      by the follicular tissue of the domestic fowl (Gallus domesticus).
AB  - Chicken granulosa and theca cells were isolated from F1 and F4-6 follicles 2-4 h
      before ovulation, and the amounts of progesterone, testosterone and oestradiol
      released in the medium during incubation for 3 h, in the presence or absence of
      pregnenolone as a percursor and stimulatory drugs or inhibitory drugs, were
      measured. Progesterone synthesis by granulosa cells was stimulated with oLH or
      theophylline. Much more progesterone was synthesized when pregnenolone was added
      to the medium. The amount of testosterone produced by the granulosa cells was
      similar to that produced by the theca cells. The production of testosterone was
      increased by the addition of oLH or theophylline. Oestradiol synthesis by F4-6
      follicles was higher than by F1 follicles, and it was higher in the theca cells
      than in the granulosa cells. The addition of oLH or theophylline increased
      oestradiol synthesis in the theca cells and the granulosa cells of F4-6
      follicles. The results indicate that oestradiol can be produced from pregnenolone
      by the theca cells alone. It is possible, however, that the theca cells also take
      in the precursors for the production of oestradiol from the granulosa cells.

PMID- 1997118
TI  - Effect of dexamethasone on uterine cell death.
AB  - Oestrogen, progesterone and androgen inhibit uterine cell death after the
      depletion of oestrogen. In the present study, we investigated effects of
      glucocorticoid on death of mouse uterine cells. Castrated female mice were given
      a daily injection of 17 beta-oestradiol (0.2 microgram/mouse/day) for 3 days, and
      then an injection of 5'-[125I]iodo-2'-deoxyuridine ([125I]IdUrd) to label DNAs of
      uterine cells with 125I. Mice were killed at intervals during subsequent
      treatments, and the retention of [125I]IdUrd incorporated into the whole uterus
      was determined. On subsequent injection of vehicle only, the 125I-radioactivity
      retained in the whole uterus rapidly decreased. Injections of dexamethasone (50
      micrograms/mouse/day) reduced the loss of 125I-radioactivity slightly but
      significantly. Dexamethasone also showed synergistic effects on the retention of
      125I-radioactivity when it was daily injected together with 17 beta-oestradiol,
      progesterone or 5 alpha-dihydrotestosterone. The present results suggest that
      glucocorticoid may affect the processes involved in the uterine cell death, in a
      manner such as inhibiting the uterine cell death or delaying the removal of DNAs
      of dead cells from the uterus.

PMID- 1997119
TI  - Induction of steroidal 11 beta-hydroxylase of Cochliobolus lunatus.
AB  - The induction of steroidal 11 beta-hydroxylase of Cochliobolus lunatus was
      studied and the effect of the structure of steroid inducers and additives on the
      extent of enzyme induction determined. 21-Hydroxyprogesterone was found to be the
      best inducer and Torlak peptone 1 the best additive. A certain parallelism was
      found between the induction of 11 beta-hydroxylase of Cochliobolus lunatus and 11
      alpha-hydroxylase of Rhizopus nigricans.

PMID- 1997120
TI  - Estradiol esters can replace 17 beta-estradiol in the stimulation of DNA and
      esterase synthesis by MCF-7 cells: a possible role for the estrogen-sensitive MCF
      7 cell esterase.
AB  - In this communication we extend our earlier observations on estrogen-sensitive
      carboxyl esterases in MCF-7 human breast cancer cells able to hydrolyze esters of
      estradiol. Using either estradiol acetate or p-nitrophenyl hexanoate as
      substrates, esterase activity was found to increase 2-3-fold in MCF-7 cells
      maintained in the presence of 10(-8) M estradiol. Following sucrose density
      centrifugation, over 85% of total esterase activity was found in the cytoplasmic
      fraction. No esterase activity was found in spent media from growing cells. By
      size exclusion chromatography, estradiol acetate esterase activity exhibited a
      mol. wt of 45-50 kDa. Attempts to demonstrate incorporation of [3H]estradiol into
      estradiol fatty acid esters by the above MCF-7 cell line (203P) were
      unsuccessful, although, such incorporation could be demonstrated in two other MCF
      7 cell sublines. Incubation of the 203P cells with 10 nM [3H]estradiol in the
      presence of 0.5 mM radioinert estradiol acetate resulted in the incorporation of
      35 +/- 12% of the label into the estradiol acetate in 10 min. In the absence of
      radioinert estradiol acetate, no incorporation was observed. When MCF-7 cells
      were incubated with [3H]estradiol in the presence of a large excess of radioinert
      estradiol valerate, label was found only in estradiol valerate. Similarly, when
      the incubation was carried out in the presence of a mixture of radioinert
      estradiol acetate and valerate, label was incorporated into both esters. We
      conclude that the apparent formation of radiolabeled estradiol esters by MCF-7
      cells incubated under the above conditions, results at least in part, from an
      esterase-catalyzed exchange reaction. Under conditions where no ester hydrolysis
      could be detected in the absence of cells, valerate and stearate esters of
      estradiol were found to be as effective as unesterified estradiol in stimulating
      esterase synthesis and the incorporation of [3H]thymidine into DNA. These results
      are consistent with a model in which an intracellular esterase in MCF-7 cells can
      generate estradiol from an exogenous lipoidal steroid and elicit an estrogen
      response.

PMID- 1997121
TI  - Identification of residues essential for progesterone binding to uteroglobin by
      site-directed mutagenesis.
AB  - In order to identify amino acids directly involved in progesterone binding to
      rabbit uteroglobin we have mutated Phe 6, Tyr 21 and Thr 60 by site-directed
      mutagenesis of the uteroglobin cDNA. These residues have been postulated
      previously to participate in progesterone binding. High-level expression of the
      mutated uteroglobin cDNAs in Escherichia coli yields recombinant protein mutants
      that, like natural uteroglobin, form stable dimers, suggesting that the tertiary
      structure of the protein has not been altered. Substitution of Phe 6 by Ser or
      Ala does not change the progesterone binding characteristics. In contrast,
      replacement of Tyr 21 by Phe or Ala, drastically decreases progesterone binding.
      In addition, replacement of Thr 60 by Ala reduces the affinity for progesterone
      by a factor of three. These data suggest a direct interaction of progesterone
      with these two amino acids and support the idea of direct hydrogen bonding of the
      carbonyl (C3 and C20) of progesterone with the hydroxyl groups of Tyr 21 and Thr
      60, respectively.

PMID- 1997122
TI  - Multiple estrogen binding sites in the uterus: stereochemistry of receptor and
      non-receptor binding of diethylstilbestrol and its metabolites.
AB  - Indenestrol A (IA), an oxidative metabolite of the synthetic estrogen
      diethylstilbestrol (DES), has high binding affinity for estrogen receptor in
      mouse uterine cytosol but possesses weak biological activity. Racemic mixture of
      optically active [3H]indenestrol A (IA-Rac) was separated and purified into
      individual enantiomers on a semi-preparative scale by HPLC with a Chiralpak OP(+)
      column. The structure-activity relationship was investigated among the [3H]IA
      enantiomers (IA-R and IA-S) and [3H]DES through direct saturation binding assays
      using mouse uterine cytosol. Specific binding curves and Scatchard plots were
      obtained for each [3H]ligand; DES, IA-Rac, IA-R and IA-S. IA-S enantiomer (Kd =
      0.67) binds to the estrogen receptor with the same affinity as DES (Kd = 0.71)
      and four times higher affinity than IA-R (Kd = 2.56). The number of binding sites
      for IA-S is approximately the same as estradiol, DES and IA-Rac while IA-R binds
      far fewer sites than the other ligands. Saturation binding assays indicated that
      [3H]DES and [3H]IA enantiomers exhibited a higher level of non-specific binding
      to the cytosol receptor compared to estradiol which has a low level of non
      specific binding. These binding studies led to the detection of an additional
      binding component for the stilbestrol compounds in estrogen target tissue cytosol
      preparations. Sucrose density gradient separation assays under low salt
      conditions showed that both [3H]DES and [3H]IA compounds bound to the 8S form of
      the receptor, the same as E2. But, in addition both DES and IA bound to another
      binding component in 4S region. The binding to the 4S component were partially
      displaced by the addition of excess unlabeled E2 and DES. Further
      characterization of the 4S component is described.

PMID- 1997123
TI  - Transcortin in rat kidney: subcellular distribution of transcortin-synthesizing
      polyribosomes.
AB  - The [3H]corticosterone-transcortin complexes from kidney cytosol show elution
      positions on DEAE-cellulose identical to serum transcortin. The incorporation of
      14C-labeled amino acids into anti-transcortin-precipitable material of kidney
      slices has been measured and compared with that of serum transcortin. It was
      established that kidney synthesized transcortin with an apparent molecular weight
      of 66 kDa on SDS-electrophoresis which resembles serum corticosteroid-binding
      globulin. Studies on the binding of [125I]anti-transcortin-IgG to membrane-bound
      rat kidney polyribosomes revealed an association of [125I]anti-transcortin-IgG
      with a discrete polyribosome fraction in the heavy polyribosome region; free
      polyribosomes were devoid of antigenic material able to bind antibodies to
      transcortin.

PMID- 1997124
TI  - Measurement of 4 urinary C-18 oxygenated corticosteroids by stable isotope
      dilution mass fragmentography.
AB  - The cortisol C-18 oxidation pathway leading to the production of 18-hydroxy- and
      18-oxocortisol is expressed in adenomatous primary aldosteronism and
      glucocorticoid remediable aldosteronism. In order to better define the
      significance of the pathway and its usefulness in differential diagnosis, we have
      developed a stable isotope dilution mass fragmentographic method for the
      determination of the tetrahydro metabolites of aldosterone, 18
      hydroxycorticosterone and 18-oxocortisol and of unmetabolized 18-hydroxycortisol
      in urine. Stereochemically correct tetrahydro steroids containing 3 deuterium
      atoms were synthesized from the available 3-keto-4-pregnenes in 2 steps and 1,2
      deuterium-labeled 18-hydroxycortisol was prepared by selective deuteration of the
      1,2-double bond of a dienone precursor. Simultaneous measurement of the 4
      steroids permitted a comparison of the abnormal products of the C-18 oxidation of
      cortisol with the normal C-18 oxidation products of corticosterone, 18
      hydroxycorticosterone and aldosterone. Application of the method to the
      definition of the normal range is described.

PMID- 1997125
TI  - Evidence for the presence of androgen receptors in human Leydig cells.
AB  - Localization of androgen receptors (ARs) in the human testis Leydig cells was
      examined with an AR assay and Northern blot analysis. Leydig cells, highly
      purified on a Percoll gradient, were used for the experiments. AR concentration
      in the total cell extract containing both the cytosol and nuclear fractions in
      Leydig cells was measured using [3H]methyltrienolone. ARs in Leydig cells showed
      a high affinity for [3H]methyltrienolone and the Kd and Bmax of the receptors
      were 1.24 nM and 11.7 fmol/mg protein, respectively. Northern blot analysis,
      using a 32P-labeled full-length human AR complementary DNA (cDNA) detected a 9.5
      kb hybridizing band in the total RNA extracted from Leydig cells. These data can
      be interpreted as evidence of the existence of ARs in human Leydig cells.

PMID- 1997126
TI  - Follicular fluid steroid levels in relation to oocyte maturity and in vitro
      fertilization.
AB  - Steroid levels in follicular fluid (FF) obtained from stimulated ovaries in
      patients undergoing in vitro fertilization (IVF) were measured by capillary gas
      chromatography. The correlation between these levels and the maturity of the
      oocyte, judged from the morphology of the oocyte corona cumulus complex (OCCC)
      and the fertilizability of the oocytes was analysed. Oocyte maturity was
      associated with higher FF levels of progesterone, 17-hydroxyprogesterone, 16
      alpha-hydroxyprogesterone and 20 alpha-dihydroprogesterone. Follicular fluids
      containing oocytes that became fertilized had significantly higher levels of 20
      alpha-dihydroprogesterone and progesterone and lower levels of androstenedione.
      Of all the steroids determined, 20 alpha-dihydroprogesterone provides the most
      significant group differences. Enhanced 20 alpha-dihydrogenation in the presence
      of decreased 16 alpha- and 17-hydroxylation appears to be an important
      characteristic of the ultimate ripening stages and early luteinization, at least
      in stimulated cycles.

PMID- 1997127
TI  - Inhibitory effect of some imidazole antifungal compounds on the synthesis of 16
      ene-C19-steroid catalyzed by pig testicular microsomes.
AB  - The activity of the enzyme (16-ene-C19-steroid synthesizing enzyme) responsible
      for the conversion of C21-steroids to 16-ene-C19-steroids, which was localized on
      pig testicular microsomes, was inhibited by some typical imidazole antifungal
      compounds such as clotrimazole, econazole, miconazole and ketoconazole which are
      known to be universal inhibitors of cytochrome P-450-dependent enzymes. The 50%
      inhibitory concentrations of clotrimazole, econazole and miconazole were 0.29,
      0.36 and 1.25 microM, respectively for 16-ene-C19-steroid synthesizing enzyme
      activity. Clotrimazole was the most powerful inhibitor of all the compounds
      examined, which shows the competitive inhibition for 16-ene-C19-steroid
      synthesizing enzyme activity. The Ki-value was 0.26 microM for its activity. The
      degree of the inhibition by these imidazole compounds was very similar to the
      inhibition of 17 alpha-hydroxylase and C17,20-lyase activities on pig testicular
      microsomes.

PMID- 1997128
TI  - The effect of short-term dietary supplementation with glucose on gastric emptying
      in humans.
AB  - In order to test whether gastric motility can adapt to changes in nutrient load,
      gastric emptying of hyperosmotic glucose and protein drinks was measured by
      applied potential tomography in two groups of ten volunteers following dietary
      supplementation with 400 g glucose/d for 3 d. The half emptying time for the
      glucose test meal was significantly faster after the standard diet had been
      supplemented with glucose compared with the standard diet alone (median and
      range, 20.7 (4.6-36.8) v. 29.1 (19.8-38.4) min; P less than 0.05), while the
      emptying of the protein drink (Oxo; Brooke Bond Ltd) was unchanged (median and
      range, 18.0 (12.5-23.6) v. 16.1 (9.6-22.7) min). These results suggest that rapid
      and specific adaptation of the small intestinal regulatory mechanisms for gastric
      emptying of nutrient solutions can occur in response to increases in dietary
      load. This adaptation may be explained by desensitization of nutrient receptors
      or by a reduction in the area of receptor field exposed to nutrients caused by
      increased absorption of glucose in the upper small intestine.

PMID- 1997129
TI  - Measurement of milk intake: tracer-to-infant deuterium dilution method.
AB  - The tracer-to-infant deuterium dilution method for the measurement of milk intake
      was evaluated in twenty breast-fed and twenty formula-fed infants. The isotope
      method was compared with conventional direct-weighing techniques. Human milk
      intake was assessed by 5 d test-weighing. Intakes of formula, supplemental foods,
      and water were determined by pre- and post-weighing of feeding bottles. An oral
      dose of 200 mg 2H2O/kg body-weight was given to each infant, and urine was
      sampled daily for 14 d. 2H enrichment of the urine was measured by gas-isotope
      ratio mass spectrometry. Milk intakes estimated from the deuterium dilution
      method were consistently higher than those from direct-weighing; the mean
      difference between methods was 106 (SD 47) g/d or 14% for the breast-fed group
      and 70 (SD 155) g/d or 8% for the formula-fed group. Estimates of intake for some
      infants varied substantially between the two methods of measurement. When the
      estimated values of human milk intake were corrected for environmental water
      influx and insensible water loss during breast-feeding, the relative bias
      decreased to 5%. Correction of the estimated values of formula intake for
      environmental water influx decreased the relative bias to 1-2%. The acceptability
      of the deuterium dilution method to determine milk intake depends on the goals
      and the tolerance for error in group and individual intake estimates of a given
      study.

PMID- 1997130
TI  - The effect of tea on iron and aluminium metabolism in the rat.
AB  - Weanling male Wistar rats were fed for 28 d on a semi-synthetic diet containing
      normal (38 micrograms/g) or low (9 micrograms/g) levels of iron. They were given
      water or tea infusion (20 g leaves/l water) to drink. Two further groups were
      given a normal- or low-Fe diet containing added tea leaves (20 g/kg diet). At the
      end of the study period, all rats given the low-Fe diet were severely anaemic, as
      assessed by haemoglobin, packed cell volume and liver Fe. Those given tea or the
      diet with added tea leaves showed a greater degree of Fe depletion. The blood and
      liver aluminium levels were not increased as a result of consuming tea or tea
      leaves, despite the higher Al intakes. Fe deficiency per se had no effect on Al
      absorption or retention from tea. It was concluded that the Al in tea was very
      poorly absorbed but that tea, either in the form of an infusion or as tea leaves,
      had an adverse effect on Fe status.

PMID- 1997131
TI  - Effect of various levels of selenium in wheat and meat on blood Se status indices
      and on Se balance in Dutch men.
AB  - After a 5-week period of low selenium intake, twenty-four Dutch men received 55,
      135 or 215 micrograms Se/d as Se-rich meat or bread for a 9-week period. Four
      unsupplemented subjects served as controls. Plasma Se increased more rapidly than
      erythrocyte Se levels; the increases were significantly dependent (P less than
      0.001) on Se intake level. Glutathione peroxidase (EC 1.11.1.9; GSH-Px) activity
      in platelets increased rapidly after supplementation and plateaued after 4-9
      weeks. At 10 weeks after supplementation ended, plasma Se levels and platelet GSH
      Px were still higher than the baseline values whereas erythrocyte Se levels
      continued to increase. Except for the higher erythrocyte Se levels after
      supplementation with high-Se meat, there were no differences in bioavailability
      of Se between meat and wheat products. Daily urinary and faecal Se excretions as
      well as Se retention increased with an increased Se intake irrespective of the
      form of the supplement. Regression of Se excretion v. intake indicated that 33
      micrograms Se/d is necessary to compensate for urinary and faecal losses.

PMID- 1997132
TI  - AMA's jack of all trades: broad, national marketing campaign for AMA care
      technician in progress.

PMID- 1997133
TI  - Research fraud: when the pressure to publish manifests.

PMID- 1997134
TI  - Ground war casualties: 'hard choices' for medical teams. Transporting wounded
      more difficult in Desert Storm.

PMID- 1997135
TI  - Nursing control of nursing practice is essential. Ask the nurse attorney.

PMID- 1997136
TI  - RNs oppose substituting unlicensed personnel.

PMID- 1997137
TI  - The development and evaluation of computer assisted learning for patients on
      continuous ambulatory peritoneal dialysis.
AB  - This article briefly describes the development and evaluation of six computer
      assisted learning (CAL) packages for use with renal patients on Continuous
      Ambulatory Peritoneal Dialysis (CAPD). The factors influencing the choice of CAL
      as the teaching medium are detailed, and some of the difficulties facing nurses
      involved in patient education highlighted. An outline of the development of
      program content is given and the methods to be used in the evaluation are briefly
      explored. Since data collection has only recently commenced, no conclusions can
      be drawn. However, the authors' anticipation that the study may help to make
      inroads into exploring the acceptability of CAL to patients and patient educators
      is expressed.

PMID- 1997138
TI  - Computerized patient care documentation. Educational applications in the
      baccalaureate curriculum.
AB  - This baccalaureate program integrated computerized patient care documentation
      with courses in nursing fundamentals and health assessment. Using an information
      system designed for acute care settings, students become familiar with computer
      use while learning documentation of care and other nursing skills. Computer
      literacy may be enhanced with integration of content and increased exposure to
      different information systems.

PMID- 1997139
TI  - Quality assurance system must balance functionality with data security.
AB  - The evaluation and selection of a QA system should include scrutiny of its
      security mechanisms. When the system is implemented, evaluate access by all
      users, establish security policies, and, most importantly, enforce them. Security
      features should not overburden the system to the point that it becomes
      cumbersome. As many security features as possible should be inherent in its day
      to-day operations. After all, automation is intended to provide access to
      clinical and financial information easily and quickly. QA professionals must
      weigh security issues against the need for patient and physician-specific
      performance information. Finally, include medical staff in the early stages of
      system implementation so they are aware of the security precautions you have
      taken. They will be assured that you are protecting confidential information
      while meeting the needs of both the medical staff and the quality management
      team.

PMID- 1997140
TI  - Authoring options.

PMID- 1997141
TI  - An informatics approach to complex research problems. Dynamic process modeling.
AB  - In the nursing literature, the term computer simulation refers exclusively to an
      educational tool that requires the user to respond to simulated events and to
      engage in the decision-making process. However, computer simulations are
      frequently constructed to model dynamic systems (systems that change with time)
      and to randomly simulate real life events in an effort to study complex problems.
      In this context, computer simulation is a research methodology and is used in a
      wide variety of disciplines including the behavioral sciences and business
      management. Nurses will inevitably encounter research studies where computer
      simulation has been employed. It is also very likely that this methodology will
      be used as a nursing research tool in the near future. This article introduces
      and describes the use of computers to model dynamic systems, the theory that
      supports simulation modeling as a research methodology, and the issues of model
      validation. Included are examples of four different research problems from
      diverse fields of study where computer simulation has been applied.

PMID- 1997142
TI  - New bronchoscopic instruments: a toothpick and a corkscrew.

PMID- 1997143
TI  - Nonoperative management of blunt splenic trauma in adults.
AB  - The management of isolated blunt splenic trauma in adults is controversial. The
      authors present a series of 17 patients with blunt splenic trauma who were
      selected for nonoperative management. Only one patient eventually required
      surgery, for a ruptured spleen. Complications included pneumonia (two cases) and
      pleural effusion, atelectasis and ileus (one case each). There were no deaths.
      Five patients required transfusion, for a total of 17 units of blood. The mean
      length of hospital stay was 9.4 days. Comparison with a group of 17 patients
      treated operatively during the same period showed that those treated
      nonoperatively had fewer complications, required less blood and had a similar
      length of hospital stay. The authors conclude that nonoperative management of
      selected patients with isolated blunt splenic trauma is safe, if the patient's
      condition is closely monitored.

PMID- 1997144
TI  - Wound infections in orthopedic surgery: effect of extended surveillance on
      infection rate.
AB  - Substantial evidence now exists that ongoing surveillance of surgical wound
      infections can contribute to reduced infection rates. What is not yet determined
      is whether surveillance should be limited to the postoperative hospital stay or
      should be continued after patient discharge. To determine the number of
      infections occurring after discharge, the authors contacted a random sample of
      their patients who did not have wound infections during their hospitalization
      after orthopedic surgery. This was done 30 days after the procedure. The authors
      selected 273 patients of 1375 who underwent orthopedic surgery over a 7-month
      period and were able to contact 199 (73%). At the 30-day follow-up 23 patients
      (11.6%) had wound infections, as judged by wound discharge and physician
      prescription of antibiotics in 20 and the patient's description of pus issuing
      from the wound in 3. During the same period postoperative wound infections were
      found in only 19 (1.5%) of 1278 patients who were subjected to in-hospital
      surveillance. The authors conclude that, in patients who undergo orthopedic
      procedures, the majority of wound infections occur after discharge from the
      hospital and that infection rates based only on in-hospital surveillance greatly
      under represent true surgical wound infection rates for orthopedic procedures.

PMID- 1997145
TI  - Detecting breast cancer after reduction mammoplasty.
AB  - Reductive breast surgery may give rise to parenchymal scarring that makes
      subsequent clinical and radiologic assessment of tumours difficult. The features
      that help distinguish benign from malignant lesions are discussed. Biopsy is
      still necessary. A screening protocol that includes preoperative mammography in
      patients at increased risk is proposed.

PMID- 1997146
TI  - A simplified protocol for banking bone from surgical donors requiring a 90-day
      quarantine and an HIV-1 antibody test.
AB  - The banking of femoral heads from patients who undergo total hip arthroplasty
      provides a valuable resource for orthopedic surgery. Quality assurance of the
      banked bone used in clinical procedures requires documented policies for
      screening, procuring, storing and distributing. Potential donors are screened at
      the time of donation for malignant disease, possible communicable disease, sepsis
      and high-risk life-styles. After negative culture results are confirmed and
      appropriate documentation has been completed, the bone is frozen at -70 degrees
      C. A quarantine period of 90 days follows. The donor is followed up 90 days or
      more postoperatively. At that time written consent is obtained for donation of
      the recovered tissue to the bone bank and for serology testing for human
      immunodeficiency virus (HIV-1) antibody, hepatitis B surface antigen (HBsAG),
      hepatitis B core antibody (HBcAb) and syphilis, and the donor is rescreened for
      contraindications. This protocol meets or exceeds all existing standards. The
      combination of obtaining consent and serology testing at 90 days streamlines the
      logistics of banking bone from surgical donors.

PMID- 1997147
TI  - Comparison between patellar resurfacing with an inset plastic button and
      patelloplasty.
AB  - Of 101 patients who underwent knee replacement with the Tricon P prosthesis and
      were followed up for 2 or more years, 68 had patellar resurfacing with a recessed
      press-fit plastic button and 43 patients had patelloplasty (shaving of the
      patella and removal of osteophytes). All patients were followed up for more than
      2 years. Three percent of the patients who had patellar resurfacing, later had
      patellar fractures; 4.6% of the patients who had patelloplasty initially,
      subsequently required patellar replacement. There were no instances of loosening
      of the patellar replacement. Patellofemoral aching was experienced by 7.6% of the
      patients who had patellar resurfacing and by 17.6% of those who did not. Of the
      patients who had patellar resurfacing, 61.5% could climb stairs without aids
      using the replaced side as the lead leg compared with 37.2% of the patients who
      had patelloplasty. Overall ratings of the surgical results were similar for the
      two groups. The author concludes that patellar resurfacing improves the quality
      of the result and that there are few drawbacks to the use of an inset patellar
      button.

PMID- 1997148
TI  - Etiology of prosthetic anastomotic false aneurysms: pathologic and structural
      evaluation in 26 cases.
AB  - To determine the etiology of anastomotic false aneurysms (AFAs), 26 textile graft
      specimens, removed because of AFA, were studied morphologically, histologically
      and by scanning electron microscopy. No cases of suture-related failures leading
      to AFA were found. Nine cases of frayed grafts were documented but were not the
      cause of AFA formation. In three cases, chemical degradation of the fibres, which
      may have been secondary to lipid infiltration, may have contributed to AFA
      formation. There were no cases of overt clinical infection, but the presence of
      bacteria was documented by scanning electron microscopy in 20 cases. The role of
      bacteria is not well defined, but they may be a factor in host arterial-wall
      degeneration as a cause for AFA formation.

PMID- 1997149
TI  - Parathyroid cyst: diagnosis and treatment of an unusual surgical problem.
AB  - A case of parathyroid cyst is reported in which the diagnosis was suggested when
      watery, clear fluid was aspirated from a mass found in the anterior region of the
      neck of a 34-year-old woman on routine medical examination. The diagnosis was
      confirmed by measurement of the parathormone content in the cyst fluid and by
      histologic examination of the cyst wall. Although rare, parathyroid cyst should
      be considered in the differential diagnosis of cysts in the anterior compartment
      of the neck. Surgery has been the usual treatment of such cysts, but several
      reports have been published in which repeated aspiration resulted in the
      disappearance of the cyst. If conservative treatment of a parathyroid cyst is
      unsuccessful, the cyst should be removed surgically.

PMID- 1997150
TI  - Spinal injuries in ice hockey players, 1966-1987.
AB  - A registry, established by the Committee on Prevention of Spinal Cord Injuries
      Due to Hockey, of major injuries to the spine or spinal cord sustained while
      playing ice hockey contains 117 cases entered between January 1966 and March
      1987; 112 of these injuries were sustained in Canada. Between 1981 and 1986 up to
      15 hockey related major spinal injuries were reported in Canada each year. Most
      injuries occurred in teenagers and players under 30 years of age who were playing
      in supervised games. The most common cause of injury was a push or check from
      behind, which caused the player to be catapulted head first into the boards. The
      authors describe the programs currently being implemented to prevent the
      occurrence of major spinal injuries. Unfortunately, these programs have not
      decreased the number of injuries reported annually.

PMID- 1997151
TI  - Nonoperative management for adults with blunt splenic trauma.

PMID- 1997152
TI  - Bilateral central dislocation of the hip: a case report.
AB  - Bilateral central dislocation of the hip occurs rarely. The authors report a case
      in which the patient was treated successfully by one-stage, bilateral, total hip
      arthroplasty.

PMID- 1997153
TI  - Lymphatic fistula after vascular reconstruction: a case-control study.
AB  - A retrospective case-control study was carried out to assess the importance of
      lymphatic fistulas that develop after vascular reconstruction and to determine
      the risk factors associated with them. The authors compared 35 patients who had
      lymphatic fistula after vascular reconstruction with 70 control patients, taken
      from the same database. They found a significant difference between the two
      groups only in age and indication for surgery: lymphatic fistulas were more
      likely to develop in older patients and in patients who underwent aortobifemoral
      bypass for limb salvage rather than for claudication (p less than 0.05).

PMID- 1997154
TI  - Fear of flying and surgery.

PMID- 1997155
TI  - Positional specificity for methyl-n-amylnitrosamine hydroxylation by cytochrome P
      450 isozymes determined with monoclonal antibodies.
AB  - Inhibitory monoclonal antibodies (MAbs) were used to determine the contribution
      of epitope-specific cytochrome P-450 isozymes in rat liver microsomes to
      hydroxylation of the esophageal carcinogen methyl-n-amylnitrosamine. These P-450
      catalyzed reactions form 2-, 3-, 4-, and 5-hydroxymethyl-n-amylnitrosamine,
      formaldehyde (demethylation), and pentaldehyde (depentylation). With uninduced
      microsomes from male rats, MAb 1-68-11 inhibited 4-hydroxylation by 73% and
      demethylation by 46%. This indicated the major contribution of constitutive male
      specific P-450 IIC11 to the metabolism. Inhibition studies with MAbs 2-66-3 and 1
      91-3 indicated that P-450 IIB1 contributed 19% and IIE1 35% to demethylation.
      With uninduced microsomes from females, MAb 1-68-11 produced similar inhibitions
      to those in male rats, indicating that female-specific P-450 IIC12 (which is
      closely related to IIC11) also catalyzed 4-hydroxylation and demethylation. With
      microsomes from 3-methylcholanthrene-induced male rats, P-450 IA1 and/or IA2 were
      responsible for 60% of 3-hydroxylation and 40% of depentylation. With microsomes
      from phenobarbital-treated rats, P-450 IIB1 and IIB2 catalyzed all 6 reactions
      but especially 4-hydroxylation and depentylation, which were 50-75% inhibited by
      MAb 2-66-3. Microsomes from Aroclor-induced males behaved as if they were induced
      by both 3-methylcholanthrene and phenobarbital. After treatment with isoniazid (a
      P-450 IIE1 inducer), inhibition by MAb 1-91-3 indicated a 45% contribution of P
      450 IIE1 to demethylation, and both P-450 IIE1 and IIB1 (or IIB2) appear to have
      been induced. A major finding with uninduced microsomes was the high specificity
      of MAb 1-68-11 for inhibiting 4-hydroxylation, indicating that P-450 IIC11 and
      IIC12 catalyzed most of this omega-1-hydroxylation. In microsomes from induced
      rats, the MAb inhibitions showed the role of the induced P-450 IA1 (or IA2), IIB1
      (or IIB2), and IIE1 in methyl-n-amylnitrosamine hydroxylation at different
      positions, as well as the presence of P-450 IIC11. This study illustrates the
      usefulness of inhibitory MAbs for defining the contribution of individual P-450s
      to position-specific metabolism.

PMID- 1997156
TI  - Purification and properties of an esterase from human breast cyst fluid.
AB  - Levels of estradiol 17 beta-ester hydrolytic activity in the breast cyst fluid
      (BCF) from 25 different women with fibrocystic disease of the breast were found
      to vary over a wide range (0-2.4 nmol/min/mg protein for estradiol acetate). On
      the basis of electrophoretic mobility on agarose gels, the activity from
      different individuals appeared to be identical. The esterase activity from a
      single BCF sample was purified to near homogeneity by differential ammonium
      sulfate precipitation, ion-exchange, and hydrophobic interaction chromatography.
      Sodium dodecyl sulfate-polyacrylamide gel electrophoresis, after the final
      purification step, showed two bands with molecular weights of approximately
      22,000 and 23,000, neither of which was immunoreactive with a rabbit antibody
      raised to a crude esterase-free BCF preparation. Esterase activity could be
      demonstrated after extraction and renaturation of the protein eluted from the Mr
      22,000 band. Resolution of the gel, however, was not good enough to rule out the
      presence of esterase activity in the Mr 23,000 protein. High performance liquid
      chromatography gel exclusion chromatography indicated a molecular weight of
      90,000-95,000 for the esterase activity in crude BCF and approximately 225,000
      for the purified activity, suggesting the native protein to be a tetramer which
      aggregated during purification. Although the natural substrate of the BCF
      esterase is unknown, the enzyme is able to cleave a variety of esters including
      acetate, valerate, and stearate esters of estradiol and p-nitrophenyl hexanoate.
      It is completely inhibited by diisopropylflurophosphate and diethylnitrophenyl
      phosphate and partially inhibited by NaF and ebelactone. The substrate and
      inhibitor profile of the enzyme indicates that it is a "B"-type carboxylesterase
      and not a protease. A comparison of the properties of the BCF esterase with those
      of esterases from the formed elements of the blood or from plasma suggests that
      the BCF esterase is not of blood origin and is probably derived from the cyst
      itself. Physiologically inactive lipoidal estrogens have been shown to be present
      in many human body fluids and tissues and it is possible that these esters serve
      as storage forms of the active hormone in hormonally sensitive tissues where the
      free steroid could be regenerated by hydrolysis.

PMID- 1997157
TI  - Stage-specific increases in cathepsin B messenger RNA content in human colorectal
      carcinoma.
AB  - Cathepsin B mRNA levels and banding patterns were characterized in human
      colorectal mucosa and carcinoma tissues from patients with tumors of different
      Dukes' stages. Quantitation of mRNA content using slot blot hybridization
      demonstrated an increase in cathepsin B message in seven of eight tumor tissues
      with an average increase of 3.5-fold over patient-matched control mucosa samples.
      This tumor-specific increase in cathepsin B mRNA confirms and extends our
      previous observation that cathepsin B enzyme specific activity levels are
      significantly elevated in colorectal carcinomas. In fact, the increase in mRNA
      levels is greater and more consistent than the observed increase in enzyme
      activity, suggesting that posttranscriptional or posttranslational regulation of
      cathepsin B expression occurs in colorectal tumors. The mRNA data also support
      our earlier observation that cathepsin B enzyme activity levels are inversely
      correlated with Dukes' stage. The tumor-specific increase in cathepsin B mRNA
      content is almost 4 times greater in earlier stage (Dukes' A and B) tumors than
      in later stage (Dukes' C and D) tumors. Thus, increased cathepsin B gene
      expression is particularly characteristic of tumors which are in the process of
      invading the bowel wall or local tissues compared with tumors which have already
      spread to more distant sites. Northern blot data on cancer/normal pairs indicate
      that the increase in cathepsin B mRNA in colorectal carcinoma is due primarily to
      changes in the amount of the 2.2- and 4.0-kilobase transcripts which are seen in
      control tissue. However, low levels of two additional cathepsin B mRNA
      transcripts (1.5 and 3 kilobases in size) were also observed in tumor tissue.

PMID- 1997158
TI  - Activation of protooncogenes in spontaneously occurring non-liver tumors from
      C57BL/6 x C3H F1 mice.
AB  - The C57BL/6 x C3H F1 (hereafter called B6C3F1) mouse is an important animal model
      for long-term carcinogenesis studies. Maintained under normal laboratory
      conditions, these mice develop various types of spontaneous tumors during their
      lifetime. Activated Ha-ras genes have been detected in 66% of spontaneous
      hepatocellular tumors in the B6C3F1 mouse [Reynolds et al., Science (Washington
      DC), 237:1309, 1988]. In this study 49 spontaneous non-liver tumors were
      investigated for oncogene activation by DNA transfection techniques. Of the 49
      tumor DNAs analyzed, only 5 yielded multiple foci in the NIH 3T3 focus assay: 2
      of 10 pulmonary adenocarcinomas; 0 of 25 lymphomas; 2 of 2 Harderian gland
      adenomas; 0 of 1 adenocarcinoma of the small intestine; 1 of 6 malignant skin
      tumors; 0 of 4 hemangiosarcomas; and 0 of 1 lung metastasis of a hepatocellular
      carcinoma. DNA from six lymphomas which were negative in the NIH 3T3 focus assay
      were further analyzed for transforming genes by the nude mouse tumorigenicity
      assay. One of the five lymphomas tested positive with this assay. Southern blot
      analysis identified five activated ras genes: H-ras in two Harderian gland
      adenomas; K-ras in one pulmonary adenocarcinoma and in one s.c. adenocarcinoma;
      and N-ras in one lymphoma. The mutations involved were CG to AT and AT to TA in
      codon 61 of the Ha-ras genes, GC to AT or TA in codon 12 of the K-ras genes, and
      a GC to AT mutation in codon 12 of the N-ras gene. Transformant DNA from a
      pulmonary adenocarcinoma which yielded multiple foci in the transfection assay
      did not hybridize to DNA probes specific for the K-, H-, and N-ras, raf, neu, and
      met genes. Thirteen additional tumor DNAs yielded a single focus in the NIH 3T3
      transfection assay. The transformant DNAs retransmitted in a second cycle
      transfection assay. Rearranged and/or amplified raf genes were detected in six of
      the transformant DNAs. At present we do not know whether these activated raf
      genes were present in the original tumor DNA. The other seven transformant DNAs
      did not hybridize with any of the above mentioned specific DNA probes utilized in
      Southern blot analysis. Unlike liver tumors, the activation of ras protooncogenes
      is not a frequent event in the development of spontaneous non-liver tumors of the
      B6C3F1 mouse. The results from this study should aid in understanding the
      neoplastic development associated with exposure to chemical carcinogens in the
      B6C3F1 mouse.

PMID- 1997159
TI  - Camptothecin, teniposide, or 4'-(9-acridinylamino)-3-methanesulfon-m-anisidide,
      but not mitoxantrone or doxorubicin, induces degradation of nuclear DNA in the S
      phase of HL-60 cells.
AB  - Short-term (2-6 h) exposure of human promyelocytic HL-60 cell cultures to the DNA
      topoisomerase I inhibitor camptothecin (0.05-0.5 microgram/ml) or to the
      topoisomerase II inhibitor, teniposide (VM-26; 0.3-3.0 micrograms/ml) or 4'-(9
      acridinylamino)methanesulfon-m-anisidide (amsacrine; 0.8 microgram/ml) triggered
      rapid degradation of DNA specifically in S-phase cells. As a result of the
      selective death of S-phase cells, only G1 cells remained in these cultures. On
      the other hand, mitoxantrone (0.02-0.4 microgram/ml) or doxorubicin (adriamycin;
      0.4-10.0 micrograms/ml) did not induce DNA degradation in S phase but arrested HL
      60 cells in S and G2 phases. In contrast to HL-60 cells, human lymphocytic
      leukemic MOLT-4 cells responded to all of these drugs (camptothecin, teniposide,
      amsacrine, mitoxantrone, and adriamycin) at all concentrations tested, invariably
      by being arrested in G2 and S phases and also by entering a higher DNA ploidy
      cycle. The data illustrate the differences in the sensitivity of S-phase cells in
      myelogenous versus lymphocytic leukemic lines to both DNA topoisomerase I and II
      inhibitors and emphasize the tissue (leukemia type)-specific factors that
      modulate the cytostatic and cytotoxic effects of these inhibitors. The
      qualitatively different response of HL-60 cells to camptothecin, teniposide, or
      amsacrine (by rapidly triggered DNA degradation in S phase) as compared to
      mitoxantrone or adriamycin (by cell arrest in G2 and S) suggests that, despite
      the generally assumed common mode of action attributed to these drugs (i.e., via
      stabilization of the cleavable DNA-topoisomerase complexes), there are
      significant differences in the mechanisms by which they exert
      cytostatic/cytotoxic effects.

PMID- 1997160
TI  - Immortalization of Syrian hamster embryo cells is in itself a multistep event.
AB  - The hypothesis that induction of immortalization of rodent cells follows one-hit
      kinetics was tested by the determination of frequencies of immortalization of
      Syrian hamster embryo cells after treatment with benzo(a)pyrene, X-rays, or
      ethylnitrosourea. Contrary to expectation, immortalization did not occur in a
      single step. Full immortalization appeared to be a process which required at
      least three steps: extension of life span (step 1), increase in cloning
      efficiency (step 2), and increase in growth rate (step 3). These three steps
      occur in this fixed sequence. The first step appears to be induced by the
      carcinogenic treatment, while the two other steps occur spontaneously in the
      progeny of cells which underwent the first step. The frequency of induction of
      the first step is in the order of magnitude of mutation induction, which suggests
      that mutation in one allele of a limited number of loci is sufficient to initiate
      the process of immortalization. However, the spontaneous frequency of
      immortalization is below 2.4 x 10(-9)/cell/generation, which appears to be too
      low for a spontaneous mutation frequency. The frequencies/cell/generation of the
      second and the third step are in the order of magnitude of spontaneous mutation
      frequencies.

PMID- 1997161
TI  - Intercellular transfer of drug resistance.
AB  - The effect of L-phenylalanine mustard (L-PAM) on heterogeneous cell populations
      containing sensitive and resistant cells was evaluated by flow cytometric
      analysis of DNA damage. Cell cultures were treated with L-PAM for 1 h, fixed, and
      stained with anti-DNA monoclonal antibody which detects DNA damage induced by
      alkylating agents. DNA damage was significantly lower in sensitive A2780 cells
      cocultured with resistant A549 or A2780/PAM cells than in A2780 cells grown
      separately. Decrease of DNA damage in sensitive cells did not occur when
      sensitive and resistant cells were grown in common medium without direct contact.
      Transfer of drug resistance in cocultures was prevented by phorbol ester which is
      known to inhibit metabolic cooperation via cell junctions. Treatment of
      cocultures with buthionine sulfoximine increased DNA damage in resistant cells
      and prevented decrease of DNA damage in sensitive cells. Glutathione (GSH)
      content in A2780 cells cocultured with A549 cells was significantly higher than
      GSH content in A2780 cells grown separately. We conclude that decreased response
      of sensitive cells in cocultures was induced by contact transfer of GSH from GSH
      rich resistant cells to sensitive cells. Intercellular transfer of drug
      resistance demonstrated by analysis of DNA damage was confirmed by colony
      formation assay. Treatment with L-PAM and Adriamycin killed all cells in
      A2780/MDR and A549 cultures. Coculture of these lines survived combination
      treatment because transfer of GSH to multidrug-resistant cells from GSH-rich A549
      cells induced resistance to L-PAM and Adriamycin in a single cell. The presence
      of 2% A549 cells increased resistance of A2780/MDR cells to L-PAM. Phorbol ester
      eliminated resistance of coculture to combination treatment. Metabolic
      cooperation between cell subsets with different mechanisms of drug resistance
      induced resistance to treatment with drugs of different classes (multiclass drug
      resistance). Inhibition of cell cooperation may improve the response of tumors to
      combination chemotherapy.

PMID- 1997162
TI  - Relationship of acivicin-induced monocytoid differentiation of human myeloid
      leukemia cells to acivicin-induced modulation of growth factor, cytokine, and
      protooncogene mRNA expression.
AB  - We have previously noted that the glutamine antagonist acivicin (alpha S,5S-alpha
      amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid) induces monocytoid
      differentiation of freshly isolated human myeloid leukemia cells and HL-60 cells.
      This study was designed to determine the effects of acivicin on the levels of HL
      60 cell mRNA transcripts of several cytokines, growth factors, and protooncogenes
      implicated in the control of hematopoietic cell proliferation and
      differentiation. Control HL-60 cells did not express mRNA for granulocyte-colony
      stimulating factor, granulocyte-macrophage-colony-stimulating factor, interleukin
      3, or interleukin 6, and acivicin or phorbol myristate acetate did not induce
      their expression. Phorbol myristate acetate reduced expression of c-myc, c-myb,
      and heat shock protein 70 and enhanced those of macrophage-colony-stimulating
      factor and c-fms. Acivicin caused a decreased expression of c-myc, and an
      increased expression of mRNA for interleukin 1 beta and tumor necrosis factor
      alpha (TNF-alpha). The drug also caused an initial increase in c-myb, followed by
      a subsequent decrease below baseline levels. Supernatants and lysates of acivicin
      treated HL-60 cells contained increased levels of interleukin 1 beta. Both TNF
      alpha and interleukin 1 beta have been shown previously to influence
      hematopoietic cell differentiation. In our experiments, exogenous interleukin 1
      added to HL-60 cells did not induce differentiation, but the combination of
      interleukin 1 and TNF synergistically enhanced the process. Pretreatment of the
      cells with TNF enhanced their responsiveness to subsequent treatment with
      interleukin 1. Our results demonstrate that the glutamine antagonist acivicin
      modulates HL-60 cell expression of TNF-alpha, interleukin 1 beta, c-myc, and c
      myb and suggest that interleukin 1 beta and TNF-alpha might (in an autocrine
      manner) cause the differentiation.

PMID- 1997163
TI  - A mathematical model relating response durations to amount of subclinical
      resistant disease.
AB  - A mathematical model is presented which seeks to determine, from examination of
      the response durations of a group of patients with malignant disease, the mean
      and distribution of the resistant tumor volume. The mean tumor-doubling time and
      distribution of doubling times are also estimated. The model assumes that in a
      group of patients there is a log-normal distribution both of resistant disease
      and of tumor-doubling times and implies that the shapes of certain parts of an
      actuarial response-duration curve are related to these two factors. The model has
      been applied to data from two reported acute leukemia trials: (a) a recent acute
      myelogenous leukemia trial was examined. Close fits were obtained for both the
      first and second remission-duration curves. The model results suggested that
      patients with long first remissions had less resistant disease and had tumors
      with slower growth rates following second line treatment; (b) an historical study
      of maintenance therapy for acute lymphoblastic leukemia was used to estimate the
      mean cell-kill (approximately 10(4) cells) achieved with single agent, 6
      mercaptopurine. Application of the model may have clinical relevance, for
      example, in identifying groups of patients likely to benefit from further
      intensification of treatment.

PMID- 1997164
TI  - Survival and causes of death in thyroid cancer: a population-based study of 2479
      cases from Norway.
AB  - Survival and prognostic factors were studied in 2479 clinically presenting
      thyroid cancers (TC) reported from the entire Norwegian population from 1970 to
      1985. Complete follow-up was obtained (median, 48 months), with information on
      causes of death. At the end of the observation period, 498 patients were reported
      to have died of TC, representing 69.7% of all deaths. Among 216 patients dying of
      other main causes, TC was considered to be a contributing cause of death in 80
      cases (11.2%). Multivariate regression analysis of TC deaths showed no
      significant difference according to sex in any of the histological types. Age had
      a strong impact on survival, and for papillary carcinomas this effect was
      apparent after the age of 55 years. Marked differences were observed between
      various histological types, even between papillary and follicular carcinomas when
      interactions were included. Furthermore, tumor stage was a strong predictor of TC
      deaths, and a reduced survival was also found in patients with lymph node
      metastases. In conclusion, the importance of age, histological type, and tumor
      stage as major prognostic factors has been documented in this population-based
      study from Norway.

PMID- 1997165
TI  - Quantitative determination of N-glycolylneuraminic acid expression in human
      cancerous tissues and avian lymphoma cell lines as a tumor-associated sialic acid
      by gas chromatography-mass spectrometry.
AB  - N-Glycolylneuraminic acid (NeuGc) is distributed in most animals except humans
      and chickens. However, human and chicken cancerous tissues often synthesize this
      heterophilic sialic acid as a tumor-associated Hanganutziu-Deicher antigen [M.
      Naiki and H. Higashi, Adv. Exp. Med. Biol., 152: 445-456, 1982; H. Higashi et
      al., Cancer Res., 45: 3796-3802, 1985]. In this paper, NeuGc in human cancerous
      tissues and chicken Marek's disease lymphoma cell lines was determined
      quantitatively with gas chromatography-mass spectrometry analysis using mass
      fragmentography. The detectable limit of NeuGc was 40 pg (0.12 pmol) in each
      injection using 5 ng of trideuteriomethyl ester trideuteriomethyl glycoside of
      the sialic acid as an internal standard sample when a pair of ions at m/e 386 and
      389 was chosen for ion monitoring. NeuGc was detected in ganglioside-rich
      fractions of various human cancerous tissues from 5 of 8 patients examined but
      was not detected in glycosphingolipids of normal human tissues. The contents of
      NeuGc in these cancerous tissues ranged from 0.02 to 0.5% of the total sialic
      acid content. NeuGc was also detected in freeze-dried samples of 5 different cell
      lines from chicken Marek's disease lymphomas but was not detected in a cell line
      from chicken lymphoid leukosis lymphoma and normal chicken skeletal muscle
      tissue. The contents of NeuGc in the positive cell lines ranged from 0.03 to
      0.11% of the total sialic acid content. These results indicate that NeuGc can be
      synthesized in both humans and chickens in some cancers.

PMID- 1997166
TI  - Biosynthesis of O-glycans in leukocytes from normal donors and from patients with
      leukemia: increase in O-glycan core 2 UDP-GlcNAc:Gal beta 3 GalNAc alpha-R
      (GlcNAc to GalNAc) beta(1-6)-N-acetylglucosaminyltransferase in leukemic cells.
AB  - We have studied the biosynthesis of altered O-glycan structures on leukocytes
      from patients with chronic myelogenous leukemia and with acute myeloblastic
      leukemia (AML). It has been shown previously that the activity of CMP-NeuAc:Gal
      beta 1-3GalNAc alpha-R (sialic acid to galactose) alpha(2-3)-sialytransferase (EC
      2.4.99.4) is increased in leukocytes from patients with chronic myelogenous
      leukemia (M. A. Baker, A. Kanani, I. Brockhausen, H. Schachter, A. Hindenburg,
      and R. N. Taub, Cancer Res., 47: 2763-2766, 1987) and with AML (A. Kanani, D. R.
      Sutherland, E. Fibach, K. L. Matta, A. Hindenburg, I. Brockhausen, W. Kuhns, R.
      N. Taub, D. van den Eijnden and M. A. Baker, Cancer Res., 50: 5003-5007, 1990).
      This increased activity may in part be responsible for the hypersialylation
      observed in leukemic leukocytes; however, hypersialylation may also be due to
      changes in underlying O-glycan structures. To test this hypothesis, we have
      assayed in normal human granulocytes and leukemic leukocytes several
      glycosyltransferases involved in the synthesis and elongation of the four common
      O-glycan cores. UDP-GlcNAc:Gal beta 1-3GalNAc-R (GlcNAc to GalNAc) beta(1-6)
      GlcNAc transferase (EC 2.4.1.102), which synthesizes O-glycan core 2 (GlcNAc beta
      1-6[Gal beta 1-3]GalNAc alpha), is significantly elevated in chronic myelogenous
      leukemia (4-fold) and AML (18-fold) leukocytes relative to normal human
      granulocytes. Neither normal nor leukemic cells show detectable activities of
      GlcNAc transferases which synthesize O-glycan core 3 (GlcNAc beta 1-3GalNAc-R)
      and core 4 (GlcNAc beta 1-6[GlcNAc beta 1-3] GalNAc-R) or the blood group I
      structure. The beta 3-GlcNAc transferase which elongates core 1 and core 2 was
      found at low levels in normal granulocytes but was not detectable in leukemic
      cells. The beta 3-GlcNAc transferase and beta 4-Gal transferase involved in poly
      N-acetyllactosamine synthesis, as well as the beta 3-Gal transferase synthesizing
      core 1 (Gal beta 3 GalNAc), were present in all samples but were significantly
      increased in patients with AML. The observed changes are consistent with
      hypersialylation in leukemia.

PMID- 1997167
TI  - Induction of invasive carcinomas in the accessory sex organs other than the
      ventral prostate of rats given 3,2'-dimethyl-4-aminobiphenyl and testosterone
      propionate.
AB  - The promotion effects of testosterone propionate (TP) on prostate carcinogenesis
      were investigated in F344 rats given the prostatic carcinogen, 3,2'-dimethyl-4
      aminobiphenyl (DMAB). One group of animals received s.c. DMAB injections at a
      dose of 50 mg/kg body weight at 2-week intervals for a total of 10 injections
      along with s.c. implantations of TP-containing Silastic tubes. A second
      experimental group of rats was given DMAB at the same dose and intervals but each
      injection of DMAB was combined with 3 prior consecutive daily 100-mg/kg body
      weight s.c. injections of TP. After cessation of carcinogen administration,
      animals in these two groups received TP implants from week 21 to the end of the
      experiment. All surviving animals were killed at week 56 and accessory sex gland
      tumor incidences were compared to those in DMAB alone and other appropriate
      control groups. The groups given TP plus DMAB and subsequent long term
      administration of TP developed lesions of the dorsolateral prostate, seminal
      vesicles, and coagulating glands which were all invasive adenocarcinomas.
      Incidences were 84.2% (16 of 19 rats) and 66.7% (12 of 18 rats), respectively.
      Macroscopic large tumors were induced in 13 animals among which 8 demonstrated
      metastasis to the abdominal cavity, liver, or lung. None of the control groups
      except for the group given TP injections plus DMAB had equivalent tumors.
      Development of carcinomas of the ventral prostate, which were all of in situ
      type, were not increased by subsequent treatment with TP. These data thus clearly
      showed that TP can exert strong enhancing effects on tumor development in the
      dorsolateral prostate, seminal vesicles, and coagulating glands but not in the
      ventral prostate.

PMID- 1997168
TI  - Upregulation of epidermal growth factor receptor induced by alpha-interferon in
      human epidermoid cancer cells.
AB  - Unregulated or increased expression of epidermal growth factor receptor (EGF-R)
      is a common event in neoplastic transformation; modulation of such a receptor by
      physiological agents could be, therefore, of clinical interest. We have studied
      the binding ability, the availability at cell surface, and the synthesis of EGF-R
      in the A431 and KB human epidermoid cancer cell lines after treatment with
      recombinant alpha-interferon (IFN-alpha). After 48 h of treatment, IFN-alpha
      induces, in both cell lines, growth inhibition and enhances class I major
      histocompatibility HLA complex expression, which is a common marker of IFN
      action. [125I]EGF total binding assessed after 48 h of treatment with IFN-alpha
      shows a dose-dependent upregulation of EGF-R binding capacity. Saturation plots
      of the binding data show that IFN-alpha treatment does not dramatically alter the
      affinity of the EGF-R and indicate that IFN-alpha only increases the number of
      low affinity receptors. We show that this effect is due to a specific increase in
      the synthesis of the receptor protein, as assessed by immunoprecipitation of
      [35S]methionine-labeled cell extracts. Electron microscopy analysis has confirmed
      an increase of EGF-R proteins at cell surface without major changes in the
      morphology of the cells. Taken together, these results indicate that IFN-alpha
      consistently induces both the binding capacity and the synthesis of EGF-R in
      human epidermoid cancer cells and suggest the use of such a mechanism for new
      anticancer therapies.

PMID- 1997169
TI  - Antigenic relationship between oval cells and a subpopulation of hepatic foci,
      nodules, and carcinomas induced by the "resistant hepatocyte" model system.
AB  - Although proliferation of small ductular-like cells, designated oval cells, is
      often observed during the early stages of chemically induced
      hepatocarcinogenesis, their role during the carcinogenic process remains
      controversial. To investigate the possibility that oval cells may give rise to
      preneoplastic lesions that ultimately progress to hepatocellular carcinomas, we
      have carried out phenotypic analysis with a panel of monoclonal antibodies to
      determine if there is an antigenic relationship between oval cells and hepatic
      foci, nodules, and tumors induced by the resistant hepatocyte model system. In
      this model, rats are given a single dose (200 mg/kg) of diethylnitrosamine,
      followed by a brief exposure to 2-acetylaminofluorene and a partial hepatectomy.
      We found that approximately 10% of the early focal lesions observed 28 days after
      diethylnitrosamine expressed either one or both of the oval cell antigens
      designated OC.2 and OV-6. By 28 weeks after diethylnitrosamine, 16 of 16 hepatic
      nodules heterogeneously expressed OV-6 whereas 5-10% of the persistent nodules
      contained scattered small hepatocyte-like cells that expressed OC.2. Examination
      of resistant hepatocyte-induced primary hepatocellular carcinomas with an
      expanded panel of monoclonal antibodies demonstrated that most cells comprising
      29 of 29 tumors expressed OV-6 and that 15-20% of the OV-6-positive tumors
      contained subpopulations of cells also expressing 3 additional oval cell
      antigens, OC.2, OC.3, and OV-1. All of the tumors examined expressed normal
      levels of the hepatocyte antigens, H.1 and HBD.1, and had dramatically reduced
      levels of H.2, H.4, and cell CAM 105 but showed elevated levels of the
      transferrin receptor, gamma-glutamyltranspeptidase, and the normal hepatocyte
      antigen, H.5. In conclusion, our findings demonstrate an antigenic relationship
      between oval cells and a subpopulation of hepatic foci, nodules, and tumors in
      the resistant hepatocyte model, suggesting that at least some primary tumors may
      be derived from oval cells in this model system.

PMID- 1997170
TI  - Differential release of active proteinase inhibitors by two rat mammary
      adenocarcinoma variants possessing different metastatic potentials.
AB  - The ability of tumor cells to express elevated levels of proteinases capable of
      degrading tissue matrix and basement membrane components in vitro has been
      correlated to their invasive and metastatic potential. Many in vitro invasion
      assays have been performed either in the presence of serum or with tumor cells
      that had been previously grown in serum. Since serum contains large amounts of
      active proteinase inhibitors, their presence could complicate interpretations. We
      have, therefore, attempted to measure the amounts of serine proteinase inhibitors
      released into culture medium by two rat mammary adenocarcinoma metastatic
      variants selected in vitro for serum-independent growth and differing in their in
      vivo metastatic behavior. Concentrated spent media (CSM) derived from cultures of
      poorly metastatic MTLn2(T42D) and highly metastatic MTLn3(T17D) tumor cells,
      grown in the presence and absence of fetal bovine serum (FBS) for 20-24 h, were
      compared for the presence of serine proteinase inhibitors capable of inactivating
      alpha-chymotrypsin. Our results show that when MTLn2(T42D) and MTLn3(T17D) tumor
      cells were exposed to FBS, the CSM of MTLn2(T42D) exhibited nearly 5-fold greater
      amounts of active proteinase inhibitors than that of MTLn3(T17D). The amount of
      proteinase inhibitory activity detected in the CSM of tumor cells not exposed to
      FBS was not eliminated but declined by 82% and 37% for MTLn2(T42D) and
      MTLn3(T17D), respectively. Analysis for enzyme-inhibitor (E-I) complex formation
      by nonreducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed
      by autoradiography confirmed the kinetic results and revealed that the major
      inhibitor present in CSM/FBS of both variants forms a heat- and sodium dodecyl
      sulfate-stable E-I complex with an apparent molecular weight of approximately
      79,000, identical to that formed when FBS or purified alpha 1-proteinase
      inhibitor is incubated with [alpha-125I]chymotrypsin. E-I complexes with apparent
      molecular weights of 44,000 and 50,000 were formed from CSM/bovine serum albumin
      of MTLn3(T17D) and MTLn2(T42D), respectively, that were not detected when [alpha
      125I]chymotrypsin was incubated with bovine serum albumin. We infer from these
      observations that, in culture, poorly metastatic MTLn2(T42D) tumor cells, as
      compared to their highly metastatic MTLn3(T17D) counterparts, exhibit an
      increased capacity to retain and subsequently release significantly greater
      amounts of serum-derived active proteinase inhibitors. Moreover, the detection of
      proteinase activity by kinetic analysis and E-I complexes by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis and autoradiography in CSM prepared
      from cultures not exposed to FBS indicates that both variants have the capacity
      to produce their own inhibitors.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1997171
TI  - A morphological and phenotypic analysis of Walker 256 cells.
AB  - A detailed morphological analysis of Walker 256 cells sensitive and resistant to
      cis-diamminedichloroplatinum(II) has been performed. Two cell populations are
      identified by electron microscopy of differing differentiation corresponding
      structurally to cells reported in experimentally induced metastases. Phenotyping
      of the cells using a number of monoclonal antibodies by immunocytochemistry and
      flow cytometry showed the absence of epithelial cell markers: however, the cells
      stained intensely for markers for germ and/or hematopoietic cells. Further
      studies utilizing monoclonal antibodies to lymphoid, myeloid, and monocytoid
      cells showed the cells to be monocytoid in origin. No evidence of cell
      heterogeneity was evident from the phenotypic experiments (a biphasic pattern was
      not observed). Enzyme histochemistry showed strong focal acid phosphatase
      activity suggestive of cells of hematopoietic origin. Thus the concept that these
      cells reflect an epithelial cell of origin is not substantiated by phenotyping
      with two methodologies.

PMID- 1997172
TI  - Measurement of capillary filtration coefficient in a solid tumor.
AB  - The net transvascular filtration rate, JF (ml/min/100 g), in an isolated, RBC
      free perfused R3230AC mammary adenocarcinoma tumor was measured using a
      gravimetric method whereby changes in tissue weight over time were monitored.
      From the gravimetric measurements of JF following changes in venous pressure, the
      capillary filtration coefficient (ml/min/mm Hg/100 g) was found to be 2.2 (range,
      0.8-2.8), i.e., 10 to 1000 times higher than those found in several normal
      tissues and within the range of those reported for glomerular capillaries. These
      measurements of capillary filtration coefficient are consistent with elevated
      tumor interstitial fluid pressure, interstitial fluid flow, and peritumor edema.

PMID- 1997173
TI  - Further studies of the action of a partially purified bacteriocin against a
      murine fibrosarcoma.
AB  - We have reported previously that a partially purified bacteriocin (PPB) from
      Escherichia coli HSC10 is toxic to KHT cells growing in vivo as micrometastases
      but apparently has no activity against a tumor growing i.m. We report here
      experiments to investigate possible reasons for this difference. The PPB was
      shown to become less effective against micrometastases, initiated by i.v.
      injection of KHT cells, as the time between cell injection and PPB treatment
      increased. The kinetics of the loss of efficacy did not, however, correlate
      exactly with the growth kinetics of the nodules as assessed by survival following
      radiation treatment at different times after cell injection. This suggests the
      possibility of a diffusion limitation although it was found that s.c. injections
      of PPB were nearly as effective against micrometastases as i.p. injections. We
      also demonstrated that the lifetime of the majority of the toxic activity of PPB
      in vivo was relatively short (less than 1 day) and that the majority of its
      effect was not caused by stimulating macrophages to act against the tumor cells.
      The PPB was found to be cytotoxic to KHT cells in vitro but the effect was
      reduced at high cell density (approximately 10(6) cells/ml). The PPB did not
      induce an immune reaction against itself in C3H mice nor was it toxic to either
      bone marrow stem cells or jejunal crypt cells at doses which were effective
      against KHT micrometastases. We conclude that PPB may have potential as a
      cytotoxic agent to act against circulating tumor cells or very small deposits of
      tumor cells but is limited in its efficacy against larger tumor masses probably
      because of diffusional and/or cell density effects.

PMID- 1997174
TI  - Uveal melanoma, hormonal and reproductive factors in women.
AB  - In a case-control study, we explored a potential association between uveal
      melanoma and reproductive factors in women. Responses from telephone interviews
      of 186 women diagnosed with uveal melanoma were compared with responses of 423
      women without this disease. All women resided in 11 U.S. western states. We
      observed a decreased risk of uveal melanoma for women who had ever been pregnant
      [relative risk (RR) = 0.60, 95% confidence interval (CI) = 0.37 -0.95], with an
      increase in this protective effect with more live births after adjustment for
      age, menopausal status, eye color, and skin sensitivity to the sun (1-2 births,
      RR = 0.47,95% CI 0.29-0.78; 3-4 births, RR = 0.38, 95% CI = 0.22-0.64; 5 or more
      births, RR = 0.33, 95% CI = 0.15-0.71). The largest effect was observed between
      nulliparous and parous women. No other reproductive factors, including use of
      oral contraceptives or postmenopausal estrogens, were shown to be related to risk
      for uveal melanoma. We conclude that most reproductive factors in this population
      play little or no role in the etiology of uveal melanoma. The association with
      number of live births must be confirmed in other studies to assure that it is
      unrelated to confounding factors not measured in this study.

PMID- 1997175
TI  - Single-dose preoperative systemic cyclophosphamide for the prevention of bladder
      tumor implantation in F344 rats.
AB  - An implantable rat bladder tumor model using the rat transitional carcinoma cell
      line 4909 was used to evaluate the effect of single-dose, preoperative, systemic
      chemotherapy on the risk of intravesical tumor implantation. To simulate the
      clinical setting in which drug levels would be present in both the tumor and the
      site of implantation, both tumor donor animals and tumor recipients were given a
      single dose of cyclophosphamide (CY) 1 h prior to tumor harvest and implantation.
      This protocol resulted in a significant reduction in the incidence of tumor
      implantation, in tumor volume, and in the incidence of nodal metastases relative
      to control animals. Dose-response experiments demonstrated that 10 of 139 (7%)
      animals treated with single doses of CY ranging from 2.5-100 mg/kg developed
      tumors as compared to 46 of 66 (70%) animals with tumors in the control groups (P
      less than 0.001). CY doses below 2.5 mg/kg were associated with an increased
      incidence of tumor implantation (19 of 45, 42%). No lethal toxicity was seen at
      doses of 50 mg/kg or less. Peak antitumor activity occurred when the CY was
      administered 1 h prior to tumor implantation as compared to 48 or 24 h before or
      1 or 24 h after tumor implantation. Preoperative "chemoprophylaxis" may be an
      effective strategy for preventing bladder tumor recurrences resulting from tumor
      implantation.

PMID- 1997176
TI  - Single-dose cyclophosphamide for the prevention of bladder tumor implantation in
      F344 rats: site of drug activity.
AB  - Previous studies demonstrated that single doses of systemic cyclophosphamide (CY)
      as low as 0.5 mg/kg are effective in preventing bladder tumor implantation in a
      rat model. In an effort to determine if the urinary bladder represents a unique
      site of CY activity, a series of experiments were performed to define the
      mechanism by which low-dose CY prevents bladder tumor implantation. Potential
      sites for CY antitumor activity include direct tumor cytotoxicity resulting from
      serum delivery of drug to the tumor; tumor cytotoxicity resulting from tissue
      drug levels at the site of implantation; altered tumor cell adherence to the
      urothelial injury site; nonspecific urothelial cytotoxicity resulting from
      urinary excretion of the CY metabolites; tumor cell-specific cytotoxicity
      resulting from urinary excretion of the CY metabolite acrolein; and second-pass
      cytotoxicity resulting from urinary excretion of the active form of CY.
      Experiments were performed to determine if a single predominant site of activity
      could be defined. Cyclophosphamide levels at the site of tumor implantation
      appeared to be the most important determinant of antiimplantation activity. Only
      tumor recipients pretreated with CY had a significant decrease in bladder tumor
      implantation. In vivo and in vitro assays measuring the effect of blood-borne
      drug delivery directly to the tumor failed to demonstrate cytotoxic activity.
      Tumor cell adherence assays measuring in vitro adherence of CY-treated tumor
      cells and in vivo adherence of tumor cells in CY-treated recipients showed no
      difference in comparison to control groups. Interval histological comparison of
      CY-treated and control bladders failed to demonstrate any difference. Urinary
      levels of acrolein did not contribute to antiimplantation activity.
      Preimplantation CY doses prevented tumor development in a s.c. implantation
      model, thereby excluding a second-pass effect resulting from urinary drug
      excretion. These data suggest that the bladder is not unique in its response to
      systemic low-dose CY administered for the prevention of implantation-mediated
      tumor recurrence. Low-dose, perioperative chemoprophylaxis may be applicable to
      other tumor systems in which intraoperative tumor dissemination is felt to
      contribute to recurrence risk.

PMID- 1997177
TI  - 19F magnetic resonance spectroscopy studies of the metabolism of 5-fluorouracil
      in murine RIF-1 tumors and liver.
AB  - The metabolism of 5-fluorouracil (5FU) in tumors and livers of RIF-1 tumor
      bearing C3H mice given i.p. injections of 5FU was serially monitored by 19F
      magnetic resonance spectroscopy. The levels of 5FU and fluoronucleotide detected
      in the tumors after a dose of 130 mg/kg (n = 13) were less than one-third of
      those after 260-mg/kg 5FU (n = 14). During the days after these doses, tumor size
      decreased by 24 +/- 3 and 52 +/- 6 SEM%, respectively. A second 130-mg/kg dose,
      given at day 7 after the first 130-mg/kg dose, resulted in still lower tumor
      fluorine levels and little change in tumor size. There was a significant
      correlation between the magnetic resonance spectroscopy-detected fluoronucleotide
      levels and the shrinkage of tumors after the 260-mg/kg dose (r = 0.44; P =
      0.024). In mouse liver, the degradation of 5FU to alpha-fluoro-beta
      ureidoprobionic acid and alpha-fluoro-beta-alanine after the 260-mg dose (n = 13)
      was slower than after a dose of 130 mg/kg (n = 14). For the respective doses, the
      half-life of 5FU was 59 +/- 7 versus 28 +/- 2 SEM min (P less than 0.0001). There
      was a negative correlation between the levels of 5FU catabolite (alpha-fluoro
      beta-ureidoprobionic acid and alpha-fluoro-beta-alanine) in liver and
      fluoronucleotide in tumor (r = -0.80; P = 0.0020), which indicates that the
      degradation in liver and the activation of 5FU in tumor are competing processes.

PMID- 1997178
TI  - Induction of alpha-N-acetylgalactosamine-O-serine/threonine (Tn) antigen-mediated
      cellular immune response for active immunotherapy in mice.
AB  - A block in carbohydrate chain elongation of O-glycosylated mucins results in
      accumulation of alpha-GalNAc O linked to serine or threonine (Tn antigen) in a
      large percentage of human adenocarcinomas. Immunization of mice with desialylated
      ovine submaxillary mucin (A-OSM), which contains a large concentration of Tn
      antigen, provided protection against challenge of a highly invasive Tn expressing
      syngeneic mouse mammary tumor, TA3-Ha. A similar protective effect was not
      observed in mice immunized with the deglycosylated mucin or irradiated TA3-Ha
      cells. Immunization with A-OSM but not with deglycosylated mucin resulted in high
      anti-Tn antibody response in mice. A-OSM induced in vitro proliferation of T
      lymphocytes obtained from mice preimmunized with A-OSM or irradiated TA3-Ha
      cells. This antigen-specific T-cell response was significantly lower if
      lymphocytes were stimulated with either the deglycosylated or sialylated form of
      mucin. A-OSM stimulation induced primarily a CD4+ T-cell population, and these
      cells secreted interleukin 2 in a dose-dependent fashion. A-OSM was also able to
      induce delayed-type hypersensitivity in mice in response to footpad injections
      with irradiated TA3-Ha cells. These studies indicate that Tn antigen presented on
      a protein backbone is capable of providing cellular immunity and protection
      against tumor in mice.

PMID- 1997179
TI  - The issues of transport multiplicity and energetics pertaining to methotrexate
      efflux in L1210 cells addressed by an analysis of cis and trans effects of
      inhibitors.
AB  - Studies are described addressing the controversial issue of the multiplicity of
      efflux routes for [3H]MTX in L1210 cells. We examined efflux multiplicity under
      conditions that do and do not maintain cellular ATP at the physiological level.
      In ATP-replete cells, the results delineate a probenecid-, bromosulfophthalein-,
      and verapamil-inhibitable route that accounts for nearly 90% of [3H]MTX efflux.
      Efflux of [3H]MTX by this route is inhibited by bromosulfophthalein in the trans
      orientation only, inhibited by probenecid only when present simultaneously in the
      cis and trans orientation and inhibited by verapamil only in the cis orientation.
      The remaining efflux of this folate analogue in ATP-replete cells appears to be
      mediated by the one-carbon, reduced folate system (MTX influx route), in that it
      is not inhibited by bromosulfophthalein or verapamil but is inhibited by the N
      hydroxysuccinimide ester of MTX, a specific inhibitor of MTX influx, and a 10
      fold higher concentration of probenecid than that required to inhibit ATP
      dependent efflux. Under these conditions, MTX did not trans-stimulate [3H]MTX
      efflux. Also, no evidence was obtained for a putative bromosulfophthalein
      insensitive, probenecid-inhibitable route for [3H]MTX efflux. In cells depleted
      to the extent of 90-95% of their ATP by 60-min incubation in medium in the
      absence of D-glucose and with 10 mM sodium azide, overall efflux of [3H]MTX was
      markedly reduced and appears to be mediated solely by the MTX influx route.
      Influx of [3H]MTX was both cis and trans inhibited by probenecid, and efflux
      under these conditions was markedly inhibited by the N-hydroxysuccinimide ester
      of MTX and trans-stimulated by MTX. Overall, the results of these studies are
      consistent with a model for methotrexate transport in L1210 cells derived [Dembo
      et al., J. Membrane Biol., 78: 9-17, 1984] in the authors' laboratory based
      solely upon a kinetic analysis of [3H]MTX influx and efflux in ATP-replete and
      depleted L1210 cells. As such, these new results identify a single ATP-dependent
      efflux route as the bromosulfophthalein-, probenecid-, and verapamil-inhibitable
      route in L1210 cells under conditions that maintain ATP levels at maximum.

PMID- 1997180
TI  - Novel gene sequences expressed by human melanoma cells identified by molecular
      subtraction.
AB  - Despite the variety of approaches used, only a limited number of tumor-associated
      antigens have been described for each histological type of tumor. In this report,
      we present a new strategy involving molecular subtraction to identify novel
      melanoma-associated gene sequences. Toward this end, 156 complementary DNA clones
      were isolated with a subtracted melanoma complementary DNA probe (melanoma minus
      lung carcinoma) after screening 2 x 10(4) independent recombinants of a melanoma
      expression library by in situ plaque hybridization. These clones were then
      polymerase chain reaction amplified, screened for duplication, and categorized
      into 53 discrete genes. By applying poissonian distribution to the numbers of
      duplicate isolates, we found most of the genes to be rare messages, present at
      less than 1 copy/200 molecules of mRNA in a typical somatic cell. Messages
      specific for a type of tissue are usually expressed in this range. The expression
      of the 53 genes was further studied in human tumor cell lines and normal tissues.
      Partial sequence data obtained for 20 complementary DNA clones revealed 8 novel
      human genes. The mRNA transcripts for 5 of the novel genes were identified by
      Northern blot analysis. Thus, molecular subtraction appears to be applicable for
      the identification of novel tumor-associated sequences. Some of the potential
      advantages and limitations of this technology are discussed, including its
      application to the molecular characterization of immunogenic melanoma-associated
      antigens.

PMID- 1997181
TI  - Models to predict outcome from childhood neuroblastoma: the role of serum
      ferritin and tumor histology.
AB  - We report on the development of three multiple logistic regression models to
      predict death from childhood neuroblastoma in patients treated without bone
      marrow transplantation. The models have been developed using a data set of 125
      patients for whom age, stage, serum ferritin, and/or histology were available
      from diagnosis. Seventy-seven patients had all four variables recorded at
      diagnosis, 34 had age, stage, and serum ferritin, and 14 had age, stage, and
      histology. Minimum time from diagnosis for all patients was 3 years. The four
      variable (full) model showed a predictive value positive rate (or 1 - the false
      positive rate) of 91.3% and a predictive value negative rate (or 1 - the false
      negative rate) of 94.4%. Survival curves, based on derived "good" and "poor"
      prognosis, were constructed for the full model of 77 patients and for the same
      patients using subset models either without ferritin or without histology.
      Correcting for prognostic factors noted at diagnosis, no time trend could be
      identified over the study period. Point estimates for the probability of death in
      all three models are displayed in graphical form. The results suggest that serum
      ferritin and tumor histology at diagnosis have independent prognostic
      significance and that patient outcome in neuroblastoma can be very accurately
      predicted with a four-variable model. Such information will help sort patients
      into good and poor prognosis for bone marrow transplant and intensive
      chemotherapy protocol triage and will help evaluate the efficacy of future
      therapeutic innovations.

PMID- 1997182
TI  - In vivo and in vitro mechanisms of drug resistance in a rat mammary carcinoma
      model.
AB  - Many in vitro tumor models have been examined to help understand the precise
      mechanisms responsible for drug resistance. The importance of these results in
      vivo remains uncertain. MatB 13762 is a rat mammary adenocarcinoma cell line that
      can be grown both in vitro and as a solid tumor in Fischer 344 rats, thus
      permitting the examination of tumor cell drug resistance under both conditions.
      Two cell lines have been selected in vitro for resistance to Adriamycin (AdrR)
      and melphalan (MlnR), respectively. Each subline has the following features:
      AdrR, increased mdr-1 messenger RNA, a high level of cross-resistance to
      vincristine and atypical low level resistance to melphalan and 1,3-bis(2
      chloroethyl)-1-nitrosourea, decreased cellular glutathione content, and increased
      expression of Yc and Yp glutathione S-transferase isozymes; MlnR, low level drug
      resistance to melphalan and cross-resistance to 1,3-bis(2-chloroethyl)-1
      nitrosourea, Adriamycin, and vincristine; increased cellular concentration of
      glutathione; elevated glutathione S-transferase activity; and greatly increased
      messenger RNA specific to the Yc and Yp glutathione-S-transferase subunits. Most
      of the biochemical and molecular features described above are present but
      significantly less prominent in tumors grown in vivo. This model provides the
      opportunity to examine the magnitude of expression and the clinical significance
      of in vitro resistance in an in vivo model.

PMID- 1997183
TI  - Partial characterization of proteoglycans isolated from neoplastic and
      nonneoplastic human breast tissues.
AB  - The biochemical composition of proteoglycans was investigated in human breast
      tissues of different age either with invasive mammary carcinoma or with benign
      lesions of the breast. Proteoglycans were extracted from tissues under
      dissociative conditions (4 M guanidine-HCl), isolated by CsCl gradient
      ultracentrifugation, and purified by gel exclusion and ion exchange
      chromatography. Glycosaminoglycan side chain compositions of proteoglycans were
      evaluated by enzymatic analysis (chondroitinases ABC and AC) and nitrous acid
      degradation. Biochemical data indicated that proteoglycans of high density and
      molecular size were increased (per wet weight of tissue) in neoplastic compared
      to nonneoplastic tissues. Overall proteoglycan content was increased almost 2
      fold in tumors. Furthermore, enzymatic data revealed a change in the proportions
      of glycosaminoglycan chains in neoplastic and nonneoplastic tissues. In
      particular, an increase in chondroitin sulfate (63% versus 35%, respectively)
      together with a decrease of dermatan sulfate (12% versus 45%, respectively)
      characterized tumors in comparison to mammary tissues with benign lesions, while
      the relative content of heparan sulfate side chains remained similar in both
      tissues. However, morphometric analyses revealed that heparan sulfate content per
      epithelial cell volume was in fact decreased in neoplastic tissue. These
      differences in proteoglycans indicate that there are significant changes in the
      extracellular matrix and surface properties of cells in breast cancer tissue.

PMID- 1997184
TI  - Increased mucosal ornithine decarboxylase activity in human gastric cancer.
AB  - The induction of ornithine decarboxylase (ODC), a key enzyme of polyamine
      biosynthesis, is an early and obligatory event in the tumor-promoting step in
      animal models. The enzyme activity is also elevated in some human premalignant
      lesions. We determined the ODC activity in human gastric cancer tissue and in the
      mucosa of cancer-bearing stomach. We concluded that gastric cancer tissue had
      significantly elevated ODC levels over those of mucosa (157.8 versus 45.7,
      respectively; P less than 0.05). Among mucosa of the stomach, that of the pyloric
      gland had higher ODC activity than that of the fundic gland (42.8 versus 21.6,
      respectively; P less than 0.05). Moreover, mucosa from the cancer-bearing stomach
      had high ODC activity compared with gastric mucosa without cancer. ODC activity
      in cancer tissue and mucosa from cancer-bearing stomach was activated by GTP. In
      rat experiments, the properties of ODC induced by gastric carcinogen were
      analyzed. Transiently induced ODC by a single gastric intubation of N-methyl-N'
      nitro-N-nitrosoguanidine was not activated by GTP whereas constitutively
      expressed ODC of N-methyl-N'-nitro-N-nitrosoguanidine-induced cancer-bearing
      stomach was activated by GTP. These results suggest that some tumor-promoting
      stimuli may be concerned in human gastric carcinogenesis and that mucosal ODC
      activity may be a useful marker for assessing the risk of gastric malignancy.

PMID- 1997185
TI  - Phase I study and pharmacological analysis of cis-diammine(glycolato)platinum
      (254-S; NSC 375101D) administered by 5-day continuous intravenous infusion.
AB  - A phase I study of cis-diammine(glycolato)platinum (254-S; NSC 375101D) was
      conducted in 15 patients with refractory or relapsing malignancy by 5-day
      continuous i.v. infusion. Three to 5 patients per dose were given 50, 75, 87.5,
      or 100 mg/m2/120 h (10-20 mg/m2 daily for 5 days). Toxicity evaluation and
      pharmacokinetic analysis were performed in 15 and 14 patients, respectively.
      Thrombocytopenia and neutropenia were the dose-limiting toxicities at the maximum
      tolerated dose of 87.5 mg/m2/120 h (17.5 mg/m2/day); however, nonhematological
      toxicities including renal toxicity, nausea and vomiting, and peripheral
      neuropathy were mild and well tolerated. The nadir of platelets and neutrophils
      was observed 4 and 5 weeks, respectively, after the initiation of drug infusion.
      Plasma and urine samples were obtained during and after infusion for
      quantification by atomic absorption spectrophotometry of total and free platinum
      levels derived from 254-S. The maximum level of total platinum was obtained after
      120 h of infusion, whereas the steady state concentration of free platinum in the
      patients given 75 mg/m2 or more was over 0.1 microgram/ml. Free platinum levels
      declined monophasically, with half-lives of 0.65-2.56 h/100 mg/m2 dose. The mean
      area under the concentration versus time curve (AUC) in the patients treated with
      75 mg/m2 was 1069 micrograms/ml, which was similar to that obtained in the
      patients receiving 100 mg/m2 of 254-S by i.v. drip infusion over 30 min. There
      was a direct correlation between the dose administered and the AUC of platinum (R
      = 0.757, P = 0.002) or the steady state plasma concentration of free platinum (R
      = 0.763, P = 0.002). The percentage of platinum excreted in urine 144 h after the
      initiation of infusion ranged from 73.1 to 100% for each dose level. No
      significant relationship was established between creatinine clearance in patients
      before treatment and the AUC or steady state concentration of free platinum. The
      plasma platinum AUC showed a linear correlation with the percentage of change in
      leukocytes [formula: see text] (R = 0.736, P = 0.003). In conclusion, the
      recommended phase II dose for a continuous infusion of 254-S is 75.5 mg/m2/120 h
      every 6 hours.

PMID- 1997186
TI  - Expression of cathepsin L in human tumors.
AB  - It has been proposed that proteases secreted by cancer cells facilitate tumor
      invasion and metastasis by degrading the components of extracellular membranes.
      The lysosomal cysteine protease cathepsin L is synthesized in large amounts and
      secreted by many malignantly transformed cells in culture. The secreted protease
      is potent in degrading collagen, laminin, elastin, and other structural proteins
      of basement membranes. To determine whether human cancers synthesize cathepsin L,
      the expression of cathepsin L in approximately 100 human tumor samples was
      determined by quantitative RNA slot blot analysis using a specific human
      cathepsin L complementary DNA probe. Results of the present study suggest that
      cancers in general express higher levels of cathepsin L than do normal tissues.
      Kidney and testicular tumors expressed the highest levels of cathepsin L; non
      small cell carcinomas of the lung expressed the next highest levels; and most
      cancers of the breast, ovary, colon, adrenal, bladder, prostate, and thyroid
      expressed elevated levels as well. Cathepsin L may prove useful as a diagnostic
      or prognostic marker of human malignancy.

PMID- 1997187
TI  - Interleukin 1 alpha blocks estradiol-stimulated growth and down-regulates the
      estrogen receptor in MCF-7 breast cancer cells in vitro.
AB  - We studied the effect of interleukin 1 alpha (IL-1 alpha) on estradiol
      stimulation of cell growth and estrogen receptor (ER) content in MCF-7 human
      breast cancer cells in vitro to determine if IL-1 alpha altered cellular
      estradiol responsiveness. We found that IL-1 alpha blocked estradiol-stimulated
      growth of these cells in a dose-dependent manner (complete antagonism at 1000
      units/ml: day 7 mean growth = vehicle, 47.7 micrograms DNA; estradiol 10(-10) M,
      95.1; IL-1 alpha/estradiol, 44.6) and at all concentrations of estradiol from 10(
      8) to 10(-11) M. IL-1 alpha in combination with trans-hydroxytamoxifen further
      inhibited estradiol-stimulated growth (vehicle = 44.8 micrograms DNA, estradiol =
      108.3, estradiol/trans-hydroxytamoxifen = 47.8, IL-1 alpha/estradiol/trans
      hydroxytamoxifen = 3.0, P less than 0.01). Inhibition with trans-hydroxytamoxifen
      was IL-1 alpha dose dependent (maximum = 97% at 1000 units/ml, P less than 0.01)
      and estradiol dose dependent (reversible with 10(-8) M estradiol, maximum
      inhibition at 10(-10) M estradiol). Concomitantly, IL-1 alpha down-regulated ER
      concentration by 38.0-43.7% (P less than 0.01) as measured by immunoreactivity or
      Scatchard analysis, respectively. This occurred as early as 3 h without a change
      in the Kd (vehicle = 0.23 nM, IL-1 alpha = 0.24 nM), persisted for at least 48 h,
      was dose dependent (maximum, 43.7% at 1000 units/ml, P less than 0.01), and was
      blocked by cycloheximide. IL-1 alpha, however, did not block estradiol
      stimulation of progesterone receptor content (vehicle = 221.9, IL-1 alpha = 238.9
      fmol/mg protein) and did not block estradiol down-regulation of ER content.
      Furthermore, IL-1 alpha alone did not alter levels of ER mRNA and did not alter
      estradiol down-regulation of ER mRNA. These findings indicate that while IL-1
      alpha antagonizes estradiol stimulation of growth and reduces ER content, its
      mechanism may involve other non-estrogen-regulated pathways.

PMID- 1997188
TI  - Cytolytic potential of peripheral blood T-lymphocytes following adoptive
      immunotherapy with lymphokine-activated killer cells and low-dose interleukin 2.
AB  - In this study, we investigated the cytolytic activity of peripheral blood T-cells
      (PBT) obtained from nine patients with primary lung cancer treated by surgical
      adjuvant adoptive immunotherapy (AIT) with lymphokine-activated killer cells and
      low-dose recombinant interleukin 2 at the time of rebound lymphocytosis (24-48 h
      after AIT). In eight of nine patients, nonspecific cytotoxicity of peripheral
      blood lymphocytes significantly increased as compared with that of pre-AIT
      peripheral blood lymphocytes. However, purified PBT showed much less activity to
      kill tumor cells although they increased in number and were activated well in
      terms of increases in the expression of HLA-DR and interleukin 2 receptor. The
      cytolytic activity of post-AIT PBT was significantly enhanced when they were
      targeted to Fc receptor-bearing tumor cells (K562 or Daudi) with anti-CD3 (NU-T3)
      or anti-T-cell receptor (TCR)alpha beta (WT31) monoclonal antibody in all five
      patients examined. Phenotypically, the targeted cytotoxicity was predominantly
      mediated by CD8+ cells. The results indicated that in vivo-activated PBT by AIT
      could not exhibit direct cytotoxicity, but they acquired cytolytic potential, the
      effect of which was expressed by targeting to tumor cells.

PMID- 1997189
TI  - Protective and restorative role of AS101 in combination with chemotherapy.
AB  - The immunomodulator AS101 has been found previously by us to stimulate the
      secretion of high levels of interleukin 1 and colony stimulating factor (CSF) in
      vitro, as well as the production of CSF in vivo in mice models. These cytokines
      are known to induce proliferation and differentiation of hematopoietic progenitor
      cells from the spleen and bone marrow (BM) and to protect mice from DNA-damaging
      agents. The present studies were designed to evaluate the effects of prolonged
      treatment with AS101 on myelopoiesis, BM cellularity, and CSF secretion in mice
      treated with a sublethal dose of cyclophosphamide (CYP) and on the survival of
      mice undergoing treatment with lethal doses of this compound. In this model, the
      hematopoietic progenitors were suppressed during the overbound phase of
      myelopoiesis resulting from the cytotoxic effects of CYP. This allowed the
      detection of a significant proliferative effect of AS101 in vivo on BM colony
      forming units granulocyte-macrophage progenitor cells, BM cellularity, and the
      secretion of CSF. Moreover, AS101 protected these animals from the lethal effects
      of high doses of CYP. These protective effects were demonstrable only when AS101
      was administered to mice prior to CYP treatment. The only exception was CSF
      secretion by spleen cells that had been reconstituted when AS101 was administered
      both prior to and following CYP treatment. AS101 was found to have a synergistic
      effect with CYP in the treatment of tumor-bearing mice, suggesting that the
      combination of these two modalities provides a more effective treatment of their
      tumors. These results strongly suggest an immunoregulatory role for AS101 in
      counteracting the chemotherapy-induced hematopoietic suppression as well as
      usefulness as adjunct treatment of cancer when used in combination with CYP.

PMID- 1997190
TI  - Significance of int-2/hst-1 coamplification as a prognostic factor in patients
      with esophageal squamous carcinoma.
AB  - The correlation between the clinical outcome in patients with esophageal squamous
      cell carcinoma and coamplification of the proto-oncogenes int-2 and hst-1, which
      are partially homologous to angiogenesis-inducing fibroblast growth factor, was
      analyzed retrospectively. Coamplification of these genes was examined by slot
      blot hybridization using DNAs extracted from formalin-fixed and paraffin-embedded
      blocks of tissues. These tissues were obtained from 107 patients with esophageal
      squamous cell carcinoma who had undergone radical surgery. Int-2/hst-1
      coamplification greater than 3-fold was observed in the primary tumors of 30 of
      107 cases (28%), and in the metastatic lymph nodes of 12 of 40 cases (30%). The
      cumulative survival rate of patients with int-2/hst-1 coamplification in the
      primary tumors was significantly lower than that of the patients without
      coamplification (P less than 0.001), and there were no significant differences
      between the clinicopathological backgrounds of the 2 groups. Int-2/hst-1
      coamplification was also significantly correlated with a high incidence of
      eventual metastasis in distant organs in these patients. These results suggest
      that int-2/hst-1 coamplification is a new biological indicator of prognosis and
      distant organ metastasis in patients with esophageal squamous cell carcinoma.

PMID- 1997191
TI  - Metabolism of carcinogenic nitrosamines by rat nasal mucosa and the effect of
      diallyl sulfide.
AB  - Rat nasal cavity is one of the target organs for carcinogenesis induced by N
      nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA), and 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). The present work investigated
      the metabolism of these nitrosamines by rat nasal microsomes, as well as the
      possible modulating factors. Microsomes prepared from rat nasal mucosa were
      efficient in metabolizing these nitrosamines. In general, the metabolism of the
      nitrosamines was slightly higher in 9-week-old rats than in 4-week-old animals,
      and there was no sex-related difference. Fasting of rats for 48 h, which is known
      to induce hepatic cytochrome P450IIE1 and NDMA metabolism, did not increase the
      nasal metabolism of NDMA, NDEA, or NNK. Pretreatment of rats with acetone,
      another inducer of hepatic P450IIE1, did not increase the metabolism of NDMA.
      Furthermore, it decreased the nasal metabolism of NDEA and NNK. Immunoinhibition
      studies suggest that, in the nasal mucosa, P450IIE1 is only partially responsible
      for the oxidation of NDMA and other P450 isozymes are responsible for the
      metabolism of NDEA. A single p.o. pretreatment of male rats with diallyl sulfide
      (DAS), a component of garlic oil, caused a significant decrease in the oxidative
      metabolism of NDEA and NNK in rat nasal mucosa. Whereas the nasal metabolism of
      NDMA was reduced by DAS pretreatment, there was no change in the amount of the
      nasal microsomal proteins immunoreactive with the antibodies against P450IIE1.
      The inhibitory effect of DAS on the nasal oxidative metabolism of NDMA, NDEA, and
      NNK was also observed in experiments in vitro. The results demonstrate the
      ability of nasal mucosa to metabolically activate these nitrosamines and the
      inhibition of this process by DAS, suggesting that DAS may be effective in
      inhibiting the related nasal tumorigenesis.

PMID- 1997192
TI  - Hyperthermia enhances localization of 111In-labeled hapten to bifunctional
      antibody in human colon tumor xenografts.
AB  - A unique bifunctional antibody (BFA) delivery system was examined for
      radiolocalization and distribution following hyperthermia (41.5 degrees C, 45
      min) of T380h human colon tumor xenografts. The BFA is an F(ab')2 fragment made
      by combining two murine monoclonal antibodies with different specificities, one
      directed against carcinoembryonic antigen (monoclonal antibody CEM 231) and the
      other (monoclonal antibody CHA 255) against a hapten found on a derivative of
      111In-labeled benzyl-EDTA (EOTUBE). This BFA is known as CEM/CHA. The CEM/CHA
      accumulates in carcinoembryonic antigen-expressing tissue and clears from normal
      tissues prior to administration of the radiolabeled hapten. T380h tumor chunks
      were injected s.c. into 31 nude mice. Two weeks later mean tumor volume was 352
      mm3 and the animals were assigned to one of four groups: (a) CEM/CHA +
      hyperthermia + 111In-EOTUBE; (b) CHA 255 F(ab')2 + hyperthermia + 111In-EOTUBE,
      and (c and d) treated in the same manner as a and b, respectively, but without
      heat. The CEM/CHA, CHA 255 F(ab')2, and 111In-labeled hapten were injected i.p.
      at 14 micrograms, 7 micrograms, and 140-200 microCi/mouse, respectively. The
      hyperthermia was administered 22-24 h after BFA and the radiolabeled hapten was
      injected 2 h later. Twenty-four h thereafter, the animals were euthanized for
      testing. A significantly greater percentage of injected radioactivity localized
      within heated compared to unheated tumors in mice given CEM/CHA and 111In-EOTUBE
      (7.39%/g tumor and 4.46%/tumor versus 2.72%/g tumor and 1.44%/tumor,
      respectively). The percentage of kidney activity in mice given CHA 255 F(ab')2
      fragments and heat was 57% lower than in the nonheated group when expressed on a
      per g basis (12.73 and 22.20%, respectively). Microautoradiography showed greater
      radiolocalization in heated tumors than in nonheated control tumors of comparable
      size. Semiquantification by immunoperoxidase staining for carcinoembryonic
      antigen did not reveal similar differences in the amounts of antigen present in
      tumors from heated and nonheated groups. These findings suggest that hyperthermia
      could be used to enhance delivery of radiolabeled haptens to prelocalized BFA
      and, thus, to enhance tumor imaging and therapeutic efficacy.

PMID- 1997193
TI  - Effect of ultraviolet irradiation on MCA102 tumor cell immunogenicity and
      sensitivity to tumor necrosis factor.
AB  - The ability of UV irradiation to induce immunogenicity of the nonimmunogenic
      major histocompatibility complex-negative MCA102 fibrosarcoma was studied. In
      parallel, the effect of short wavelength UVC light on the sensitivity of tumor
      cells to natural cell-mediated cytotoxicity and tumor necrosis factor (TNF) was
      also investigated. MCA102 fibrosarcoma cells were irradiated in vitro twice with
      UVC light (610 and 457 J/m2). Surviving cells were expanded and maintained in
      vitro as the MCA102UV subline. UV treatment changed tumor cell morphology and
      increased their in vitro rate of proliferation. However, after inoculation of 1 x
      10(5) to 2 x 10(6) MCA102UV cells into C57BL/6 mice, growth of these cells was
      completely prevented. Lyt2.2 and not L3T4 lymphocytes were responsible for the
      rejection of these tumor cells. To determine the minimal and optimal dose of UV
      irradiation capable of increasing tumor cell immunogenicity, MCA102 cells were
      irradiated once or twice with different doses (76 to 610 J/m2) of UV light. After
      a single dose of UV treatment, tumor growth in C57BL/6 mice was inhibited,
      particularly with lines irradiated at the highest doses (610 or 457 J/m2). After
      a second round of irradiation, tumor cells became more immunogenic, and the level
      of tumor growth inhibition increased with higher doses of UV irradiation. Thus,
      cells irradiated twice with 610 and 457 J/m2 became rejectable in all
      immunocompetent C57BL/6 mice. The increase in tumor cell immunogenicity induced
      by UV light was not associated with the appearance of Class I H-2 antigens. In
      parallel with the induction of tumor cell immunogenicity, UV irradiation made
      tumor cells more sensitive to natural cell-mediated cytotoxicity and to lysis by
      TNF. An increase in sensitivity to natural cell-mediated cytotoxicity and TNF was
      observed after single or double doses (152 to 610 J/m2) of UV irradiation. The
      cells that showed the highest levels of immunogenicity were found also to be most
      sensitive to lysis by TNF. MCA102UV cells cultured in the presence of increased
      doses of recombinant TNF became resistant to its cytotoxicity without losing
      their immunogenicity, suggesting that immunogenicity and TNF sensitivity are two
      independent UV-induced properties. Thus, UV irradiation appears to be an
      effective modality for altering tumor cell immunobiological properties, including
      increased tumor cell sensitivity to T-cell and/or natural cell-mediated immunity.

PMID- 1997194
TI  - Microdistribution of specific rat monoclonal antibodies to mouse tissues and
      human tumor xenografts.
AB  - Detailed evaluations of the microdistribution of 125I-labeled monoclonal
      antibodies (MoAbs) to normal tissue antigens were conducted in BALB/c mice. MoAb
      273-34A, which binds to a target molecule on the lumenal surface of lung
      endothelial cells, localizes quickly and efficiently throughout the lung
      vasculature. MoAb 133-13A, which binds to an antigen on macrophage-like cells
      expressed in nearly equal amounts in lung, liver, and spleen, localizes most
      efficiently to spleen and less well to liver and lung. The microdistribution of
      MoAb 133-13A in liver and spleen is consistent with the antigen distribution in
      these organs, but in the lung a more diffuse microdistribution is observed,
      indicating poor access of MoAb to the antigen-positive alveolar macrophages.
      These findings are consistent with the hypothesis that tight endothelium (lung)
      represents a significant barrier to extravasation of MoAb into tissue while
      fenestrated (spleen) and sinusoidal (liver) endothelium are more easily
      penetrated. In human tumor bearing nu/nu mice, the microdistribution of MoAb to
      the beta 4 and alpha 6 subunits of integrin was studied. These MoAbs do not cross
      react with murine integrins and thus are tumor-specific in the nu/nu mouse model.
      Localization of 125I-labeled MoAb 450-11A, which reacts with an intercellular
      domain of beta 4 integrin, is very weak and diffuse. All MoAbs to extracellular
      domains (mouse 450-9D, 450-30A1, and rat 439-9B) localize well to the tumor.
      Microdistribution of these MoAbs in the 3 different tumors is nonuniform with
      heavy distribution near the blood vessels, whereas antigen distribution as
      determined by immunoperoxidase shows a much more uniform pattern throughout the
      tumors. In experiments with 125I-labeled MoAb 439-9B F(ab')2, the nonuniform
      pattern of distribution was not changed. Gross and microdistribution of different
      doses of 125I-labeled MoAb 439-9B were studied. The percent of injected dose per
      g of MoAb in the tumor at 48 h did not vary significantly (P greater than 0.1) up
      to a dose of 500 micrograms/mouse, and active MoAb was recovered in comparable
      amounts in the serum from animals in all doses. In contrast, the
      microdistribution of MoAb at the high dose was different than that at low doses.
      At doses up to 100 micrograms/mouse, a perivascular pattern was obtained, whereas
      at 500 micrograms/mouse the 125I-labeled MoAb was distributed nearly evenly
      throughout the tumor. These data indicate that high doses of MoAb penetrate
      deeply into portions of the tumor that are distant from blood vessels.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 1997195
TI  - A new tumor-associated antigen expressed on breast carcinomas, defined by
      monoclonal antibody BCA 227.
AB  - After immunization of mice with the human breast carcinoma cell line MCF-7, we
      produced monoclonal antibody (mAb) BCA 227, which allowed us to characterize a
      new tumor-associated antigen. This molecule is strongly expressed by well
      differentiated mammary carcinoma cell lines and by some other tumor cell lines of
      epithelial origin. Immunohistological study of frozen sections of different
      tissues and tumors confirmed its expression by tumor cells of epithelial origin,
      particularly infiltrating duct carcinomas of the breast. The antigen is also
      expressed, to a lesser extent, by some normal epithelial cells. Its biochemical
      characterization revealed a Mr 71,000 protein without an N-linked sugar moiety.
      Six to 40 x 10(3) binding sites are present on breast tumor cell surfaces.
      Although mAb BCA 227, which was found to be of the IgG2a isotype, did not mediate
      antibody-dependent cell-mediated cytotoxicity with either human or mouse effector
      cells, a 50% inhibition of SK-BR5 tumor growth was obtained in nude mice,
      suggesting that another mechanism is responsible for this inhibition.
      Biodistribution studies of radiolabeled F(ab')2 fragments of mAb BCA 227 in tumor
      bearing nude mice showed a preferential localization in the tumor. All these data
      are in favor of the use of mAb BCA 227 as an immunodiagnostic tool for breast
      cancer.

PMID- 1997196
TI  - Interleukin 2 induced leukocyte adhesion to the normal and tumor microvascular
      endothelium in vivo and its inhibition by dextran sulfate: implications for
      vascular leak syndrome.
AB  - The maximum dose of interleukin 2 (IL-2) alone or with adoptively transferred
      lymphocytes is limited by the vascular leak syndrome, resulting from an increase
      in vascular permeability. Using intravital microscopy to quantify cell
      interaction in vivo and the Miles assay to assess changes in vascular
      permeability, we have shown that IL-2 increases both leukocyte-endothelial cell
      adhesion and vascular permeability in the cutaneous tissue of rabbits. Both of
      these processes can be reversed to a large extent using dextran sulfate (Mr
      approximately 500,000; 10 mg/kg body weight), a nonspecific blocker of leukocyte
      endothelial adhesion. These results suggest that increased leukocyte (probably
      lymphocyte) adhesion to the postcapillary microvasculature contributes
      significantly to the IL-2 induced increase in permeability. Therefore, as more
      specific inhibitors of leukocyte-endothelial adhesion become available, improved
      strategies could be developed to control or prevent IL-2 toxicity.

PMID- 1997197
TI  - Aberrant crypts: putative preneoplastic foci in human colonic mucosa.
AB  - Aberrant crypts were identified for the first time in whole-mount preparations of
      normal-appearing human colonic mucosa after staining with methylene blue. The
      foci of aberrant crypts varied from single altered glands to plaques of greater
      than 30 crypts. The mean proportion of colonic mucosa altered and the number of
      foci with aberrant crypts per cm2 of colonic mucosa were (a) higher in patients
      with colon cancer than in patients without colon cancer or predisposing
      conditions and (b) highest in our single case of Gardner's syndrome. Aberrant
      crypts are postulated to be the earliest identifiable potential precursors of
      colon cancer. Analysis of aberrant crypts may facilitate the study of the early
      pathological and molecular changes that precede colon cancer.

PMID- 1997198
TI  - 3-Methyladenine DNA glycosylase activity in a glial cell line sensitive to the
      haloethylnitrosoureas in comparison with a resistant cell line.
AB  - Extracts of a glial cell line (SF-126) which is sensitive to the cytotoxic effect
      of the haloethylnitrosoureas and of a cell line (SF-188) which is resistant to
      these agents have been tested for their ability to release methylated bases from
      a DNA substrate which has been modified with [3H]dimethyl sulfate. In comparison
      with the sensitive cell line, extracts from the resistant cell line have 2-3-fold
      higher enzymatic activity. High performance liquid chromatography profiles of the
      bases which are released by these extracts show that the activity is specific for
      3-methyladenine, suggesting that the resistant cells contain elevated levels of 3
      methyladenine DNA glycosylase. Previous studies have shown that these cells also
      contain elevated levels of O6-alkylguanine-DNA alkyl-transferase, suggesting that
      both enzyme activities may be involved in the resistance of this cell line to the
      haloethylnitrosoureas.

PMID- 1997199
TI  - Decreased levels of 1,2-sn-diacylglycerol in human colon tumors.
AB  - We have found that in 15 of 15 primary human colon tumors there was a significant
      decrease (by about 40%) in the levels of diacylglycerol when compared to paired
      adjacent normal mucosa samples. Assays on the same samples indicated that this
      decrease was seen both in tumors that did and did not display mutations in codon
      12 of c-K-ras. These results, taken together with previous studies on protein
      kinase C, suggest that the protein kinase C signal transduction pathway is
      suppressed in human colon cancer.

PMID- 1997200
TI  - Molecular cloning of the chromosomal breakpoint of a B-cell lymphoma with the
      t(11;14)(q23;q32) translocation.
AB  - The breakpoint of t(11;14)(q23;q32) chromosome translocation in a B-cell lymphoma
      line, RC-K8, was cloned. Immunoglobulin heavy chain (IGH) constant gene, C gamma
      2 at the 5' end, was involved in this translocation, and the DNA segment
      juxtaposed to the C gamma 2 was proved to be derived from chromosome 11 by
      somatic cell hybrid study. The normal counterpart of chromosome 11 was also
      isolated. With a DNA probe near the breakpoint of chromosome 11, Southern blot
      analysis of RC-K8 and 10 other cases with translocation involving the 11q23
      region was conducted, but no rearrangement bands have been observed thus far
      except for RC-K8.

PMID- 1997201
TI  - RNA editing: world's smallest introns?

PMID- 1997202
TI  - Cell signaling by second messenger waves.

PMID- 1997203
TI  - Targeted disruption of the c-src proto-oncogene leads to osteopetrosis in mice.
AB  - To understand the normal, physiological role of the c-src proto-oncogene, a null
      mutation was introduced into the gene by homologous recombination in mouse
      embryonic stem cells. Two independent targeted clones were used to generate
      chimeras that transmitted the mutated allele to their offspring. Intercrossing of
      heterozygotes gave rise to live born homozygotes, but most of these mice died
      within the first few weeks of birth. Histological and hematological examination
      of the homozygous mutants did not reveal detectable abnormalities in the brain or
      platelets, where src is most highly expressed. However, these mutants were
      deficient in bone remodeling, indicating impaired osteoclast function, and
      developed osteopetrosis. These results demonstrate that src is not required for
      general cell viability (possibly because of functional overlap with other
      tyrosine kinases related to src) and uncover an essential role for src in bone
      formation.

PMID- 1997204
TI  - A 240 kd multisubunit protein complex, CBF3, is a major component of the budding
      yeast centromere.
AB  - A key protein component (CBF3) of the budding yeast (S. cerevisiae)
      centromere/kinetochore has been purified and characterized. CBF3 is a 240 kd
      multisubunit protein complex that binds specifically to the yeast wild-type
      centromere DNA (CEN), but not to nonfunctional CEN DNA containing a single base
      substitution in the critical CDEIII consensus sequence. When purified by affinity
      chromatography, CBF3 contains three protein components: CBF3A (110 kd), CBF3B (64
      kd), and CBF3C (58 kd). Highly purified CBF3 requires the presence of a separate
      assembly factor or chaperone activity to bind to CEN DNA. Treatment with
      phosphatase inactivates CBF3, indicating that at least one of the CBF3 subunits
      must be phosphorylated for DNA binding to occur. A 56 bp region including the 26
      bp CDEIII consensus is protected from DNAase I cleavage in the CBF3-CEN DNA
      complex.

PMID- 1997205
TI  - Genes occupy a fixed and symmetrical position on sister chromatids.
AB  - A high-resolution fluorescence methodology for nonisotopic in situ hybridization
      was applied to determine the positions occupied by several single-copy genes, DNA
      sequences, and integrated viral genomes on sister chromatids. The lateral and
      longitudinal mapping of the probes was performed on prometaphase and metaphase
      chromosomes. A fixed lateral position, exterior or median in relation to the
      longitudinal axis of the chromatids, was observed for a given probe, with a
      symmetrical position of the double fluorescent spots. This position appears to be
      independent of chromosome condensation stage from prometaphase to metaphase.
      These observations suggest an opposite helical-handedness conformation of DNA on
      both chromatids with a mirror symmetry. They support the model of chromosome
      packaging recently proposed by Boy de la Tour and Laemmli. Moreover, our results
      indicate that the last stages of chromosome condensation occur by packing down
      the coils without further coiling.

PMID- 1997206
TI  - Topology of eukaryotic type II membrane proteins: importance of N-terminal
      positively charged residues flanking the hydrophobic domain.
AB  - We have tested the role of different charged residues flanking the sides of the
      signal/anchor (S/A) domain of a eukaryotic type II (N(cyt)C(exo)) integral
      membrane protein in determining its topology. The removal of positively charged
      residues on the N-terminal side of the S/A yields proteins with an inverted
      topology, while the addition of positively charged residues to only the C
      terminal side has very little effect on orientation. Expression of chimeric
      proteins composed of domains from a type II protein (HN) and the oppositely
      oriented membrane protein M2 indicates that the HN N-terminal domain is
      sufficient to confer a type II topology and that the M2 N-terminal ectodomain can
      direct a type II topology when modified by adding positively charged residues.
      These data suggest that eukaryotic membrane protein topology is governed by the
      presence or absence of an N-terminal signal for retention in the cytoplasm that
      is composed in part of positive charges.

PMID- 1997207
TI  - Mutations in the CDP-choline pathway for phospholipid biosynthesis bypass the
      requirement for an essential phospholipid transfer protein.
AB  - SEC14p is the yeast phosphatidylinositol (PI)/phosphatidylcholine (PC) transfer
      protein, and it effects an essential stimulation of yeast Golgi secretory
      function. We now report that the SEC14p localizes to the yeast Golgi and that the
      SEC14p requirement can be specifically and efficiently bypassed by mutations in
      any one of at least six genes. One of these suppressor genes was the structural
      gene for yeast choline kinase (CKI), disruption of which rendered the cell
      independent of the normally essential SEC14p requirement. The antagonistic action
      of the CKI gene product on SEC14p function revealed a previously unsuspected
      influence of biosynthetic activities of the CDP-choline pathway for PC
      biosynthesis on yeast Golgi function and indicated that SEC14p controls the
      phospholipid content of yeast Golgi membranes in vivo.

PMID- 1997208
TI  - The midline of the Drosophila central nervous system: a model for the genetic
      analysis of cell fate, cell migration, and growth cone guidance.
AB  - A row of mesectodermal cells separates the two lateral neurogenic regions in the
      Drosophila embryo and generates a discrete set of glia and neurons. Most CNS
      growth cones initially head straight toward the midline, suggesting that these
      midline cells play a key role in the formation of the axon commissures. We have
      used antibodies that stain the first axons, beta-galactosidase enhancer trap
      lines that selectively stain the different midline cells, and electron
      microscopic studies to elucidate the cells and interactions that mediate the
      normal formation of the two major commissures in each segment. This analysis has
      led to a model that proposes a series of sequential cell interactions controlling
      the development of the axon commissures. A genetic test of this model has
      utilized a number of mutations that, by either eliminating or altering the
      differentiation of various midline cells, perturb the development of the axon
      commissures in a predictable fashion.

PMID- 1997209
TI  - Inhibition of MAP2 expression affects both morphological and cell division
      phenotypes of neuronal differentiation.
AB  - Expression of the differentiated neuronal phenotype is typically manifest in
      several properties: distinct morphologies and organizations of the underlying
      cytoskeleton; appearance of specific macromolecules; and cessation of cell
      division. All of these properties are induced in undifferentiated embryonal
      carcinoma cells exposed to retinoic acid. We show here that the mRNA and protein
      for the microtubule component MAP2 is also induced by retinoic acid. Stable
      transfectants of undifferentiated cells, constitutively expressing MAP2 antisense
      RNA, show significantly reduced levels of MAP2 antisense RNA, show significantly
      reduced levels of MAP2 protein upon induction compared with controls. These cells
      do express other neuronal markers, but they do not undergo normal morphological
      differentiation nor do they withdraw from the cell cycle. The results suggest
      that MAP2 expression may be necessary for both neurite extension and cessation of
      cell division.

PMID- 1997210
TI  - Parental imprinting of the mouse insulin-like growth factor II gene.
AB  - We are studying mice that carry a targeted disruption of the gene encoding
      insulin-like growth factor II (IGF-II). Transmission of this mutation through the
      male germline results in heterozygous progeny that are growth deficient. In
      contrast, when the disrupted gene is transmitted maternally, the heterozygous
      offspring are phenotypically normal. Therefore, the difference in growth
      phenotypes depends on the type of gamete contributing the mutated allele.
      Homozygous mutants are indistinguishable in appearance from growth-deficient
      heterozygous siblings. Nuclease protection and in situ hybridization analyses of
      the transcripts from the wild-type and mutated alleles indicate that only the
      paternal allele is expressed in embryos, while the maternal allele is silent. An
      exception is the choroid plexus and leptomeninges, where both alleles are
      transcriptionally active. These results demonstrate that IGF-II is indispensable
      for normal embryonic growth and that the IGF-II gene is subject to tissue
      specific parental imprinting.

PMID- 1997211
TI  - Physical mapping across the fragile X: hypermethylation and clinical expression
      of the fragile X syndrome.
AB  - The most common genetic cause of mental retardation after Down's syndrome, the
      fragile X syndrome, is associated with the occurrence of a fragile site at
      Xq27.3. This X-linked disease is intriguing because transmission can occur
      through phenotypically normal males. Theories to explain this unusual phenomenon
      include genomic rearrangements and methylation changes associated with a local
      block of reactivation of the X chromosome. Using microdissected markers close to
      the fragile site, we have been able to test these hypotheses. We present evidence
      for the association of methylation with the expression of the disease. However,
      there is no simple relationship between the degree of methylation and either the
      level of expression of the fragile site or the severity of the clinical
      phenotype.

PMID- 1997212
TI  - Genetic studies of human apolipoproteins. XVI. APOE polymorphism and cholesterol
      levels in the Mayans of the Yucatan Peninsula, Mexico.
AB  - Structural variation at the APOE locus is a major determinant of interindividual
      differences in cholesterol levels in populations at large. We have determined
      APOE structural polymorphism and estimated its impact on total cholesterol in the
      Mayans of the Yucatan Peninsula from Mexico. A unique pattern of APOE allele
      frequency distribution was observed, with no example of the APOE*2 allele and a
      relatively low incidence (9%) of the APOE*4 allele, giving rise to the lowest
      average heterozygosity at the APOE locus observed to date. The reported elevating
      affect of the APOE*4 allele on cholesterol has been found to be absent in the
      Mayans; several possible explanations which may account for the absence of this
      affect are discussed. In addition to APOE the gene products of five other
      apolipoprotein loci were screened and low frequency variation, possibly due to
      European admixture, was observed in two systems (APOH and APOA-IV).

PMID- 1997213
TI  - Detection of mitochondrial DNA deletions in blood using the polymerase chain
      reaction: non-invasive diagnosis of mitochondrial myopathy.
AB  - Southern hybridisation demonstrates deleted mitochondrial DNAs (mtDNAs) in muscle
      but not in blood in a subgroup of patients with mitochondrial myopathy. The
      polymerase chain reaction (PCR) was used to search for low levels of rearranged
      mitochondrial DNAs in blood in 24 patients with mitochondrial myopathy, and 15
      asymptomatic relatives, all of whom have no detectable abnormality on restriction
      enzyme analysis of blood mitochondrial DNA. In eight patients and two of their
      relatives, PCR products were obtained consistent with deletions of mitochondrial
      DNA. The presence or absence of a deletion was correctly predicted in 10 out of
      11 patients from whom information was available from muscle DNA. No false
      positives were obtained in 43 controls. PCR analysis of blood may be applicable
      as a non-invasive screening test of affected individuals and in carrier
      detection.

PMID- 1997214
TI  - Anthropometric study with emphasis on hand and foot measurements in the Prader
      Willi syndrome: sex, age and chromosome effects.
AB  - Age, sex and chromosome effects on weight, height, sitting height, three head
      dimensions, and five hand and three foot measurements were analyzed from 57
      patients (35 males and 22 females) with the Prader-Willi syndrome (PWS). No
      significant differences were observed in anthropometric data between PWS patients
      with the 15q chromosome deletion and those with normal chromosomes. Preschool
      children were found to have dolichocephaly, while hand and foot measurements,
      stature and sitting height were within normal range, although foot size was
      smaller than hand size in females when compared with PWS males. However,
      anthropometric measurements, excluding weight, head length and ankle breadth,
      were less than -2 SD in adult patients. Abnormal growth patterns apparently exist
      with significant negative correlations with age, particularly in PWS males, for
      height, sitting height, head circumference, and hand and foot measurements, but a
      significant positive correlation for weight was found in patients below 10 years
      of age.

PMID- 1997215
TI  - Age of onset in vitiligo: relationship with HLA supratypes.
AB  - HLA class I (A, B, C), class II (DR, DQ) histoglobulins and HLA class III (C4A,
      C4B and Bf) complement factors were analysed in 87 patients with vitiligo and in
      controls. Two HLA supratypes seem to mark different age of onset of vitiligo: HLA
      BfS, C4A3, C4B1, DR5 (W11), DQW3 is characteristic of the pediatric form; while
      HLA-BfS, C4A3, C4B1, DR7, DQW2 marks the adult form of disease. The importance of
      defining HLA supratype, not single alleles, is discussed.

PMID- 1997216
TI  - Inv dup (8) (p21.1----22.1): further case report and a new hypothesis on the
      origin of the chromosome abnormality.
AB  - We report a male infant with a de novo inverted duplication of bands 8p 21.1---
      22.1. The clinical features up to 8 months of age and the enzyme investigations
      are described. A new cytogenetic hypothesis on the genesis of this rare
      chromosome aberration is also discussed.

PMID- 1997217
TI  - A new transthyretin variant from a patient with familial amyloidotic
      polyneuropathy has asparagine substituted for histidine at position 90.
AB  - A new transthyretin variant which lost an Sph I cleavage site within exon 3 has
      been characterized. A 260 bp sequence containing exon 3 was amplified using the
      polymerase chain reaction, and the variant was found to possess a Bsm I cleavage
      site not present in normal transthyretin. This led to the conclusion that the
      histidine at position 90 was replaced by asparagine, and amino acid analysis
      supported the conclusion. The discovery of this mutation suggests that
      intermolecular binding between hydrophobic polypeptide loops on the surface of
      transthyretin can lead to familial amyloidotic polyneuropathy.

PMID- 1997218
TI  - Tetrasomy 9p: an emerging syndrome.
AB  - An infant with non-mosaic 9p tetrasomy is described. The tetrasomy apparently
      results from a translocation involving the 9qh region. All the cells analyzed
      from multiple banding techniques from lymphocyte culture as well as skin
      fibroblast culture were 9p tetrasomic. The infant, who had the characteristic
      dysmorphic features of 9p tetrasomy, survived for 2 months. Prominent features
      included: low birth weight, severe retardation, brachycephaly with large anterior
      fontanelle, hypertelorism with short bilateral palpebral fissures, beaked nose,
      bilateral cleft lip and palate, and low-set, malformed ears. Skeletal anomalies,
      ambiguous genitalia and heart defect were also observed. These features are
      highly characteristic of the 9p tetrasomy syndrome based on six pure tetrasomy
      and four cases of tetrasomy that included part of the 9qh region.

PMID- 1997219
TI  - Recurrent neuroleptic malignant syndrome associated with inv dup(15) and mental
      retardation.
AB  - Neuroleptic malignant syndrome (NMS) is an uncommon but serious adverse reaction
      to neuroleptic drugs. Clinically, it resembles malignant hyperthermia, a
      pharmacogenetic disorder of anesthesiology. Inv dup(15) is a rare but
      underrecognized cause of mental retardation among institutionalized patients. NMS
      and inv dup(15) have not been previously reported together. Their association
      should encourage clinicians to search for genetic markers for NMS.

PMID- 1997220
TI  - Pigmentary dysplasias in long survivors with mosaic trisomy 18: report of two
      cases.
AB  - We describe two patients, a 19-year-old girl and a 19-year-old boy, with mosaic
      trisomy 18 and pigmentary dysplasias. Both patients had profound growth and
      mental retardation, marked kyphoscoliosis, bushy eyebrows, bulbous nose, simple
      ears, and joint contractures - clinical manifestations of long survivors with
      mosaic or non-mosaic trisomy 18. In addition, the boy showed total asymmetry.
      Pigmentary dysplasias of the skin with hypopigmented whorls and streaks,
      initially absent or overlooked at the ages 2 and 15 years, were detected on close
      examination. It is advisable to check closely every long survivor with mosaic or
      purportedly non-mosaic trisomy 18 for pigmentary dysplasias.

PMID- 1997221
TI  - Dizygotic twins concordant for truncus arteriosus.
AB  - Persistent truncus arteriosus (TA) is an uncommon congenital cardiovascular
      malformation, which comprises between 0.4% and 4% of all congenital heart
      defects. Occurrence of TA in siblings has been reported infrequently. Twins
      concordant for isolated TA appear to have been reported only once previously. In
      this paper, we describe dizygotic twin females who were concordant for isolated
      TA.

PMID- 1997222
TI  - Computer adapted testing for licensure.

PMID- 1997223
TI  - Trends in pediatric orthopedics.

PMID- 1997224
TI  - The new genetics and its relevance to orthopedics.
AB  - The recent advances in genetics have practical importance for patients with
      orthopedic problems. Specific genes are being isolated, mapped to chromosomes,
      and defined. Surgical specimens can be used for genetic studies to define
      specific genetic abnormalities. Making specific genetic diagnoses is important
      for appropriate care of the patient and the family.

PMID- 1997225
TI  - Application technique of Cotrel-Dubousset instrumentation for scoliosis
      deformities.
AB  - Used in over 600 cases, the posterior Cotrel-Dubousset spinal instrumentation
      device has become the device of choice. This technique allows the most effective
      correction for all kinds of spinal deformities. It requires lengthy preoperative
      planning and is a technically demanding surgical procedure; however, because of
      its versatility it can be adapted to most spinal deformities. The Cotrel-
      Dubousset technique is a rigid system of immobilization, and, because it does not
      require any postoperative immobilization, patients are able to resume their
      normal lives and activities very quickly.

PMID- 1997226
TI  - Surgical management of acetabular dysplasia.
AB  - Dysplasia of the acetabulum can be caused by malposition, insufficiency, or
      incongruity. The decision to correct acetabular dysplasia is based on the
      severity of the condition or on the condition's failure to improve and is made
      after several years of observation. Correction is best when performed in
      childhood and should be designed to meet the individual needs of the patient
      after careful consideration of the pathology, anatomy, patient's age, and skill
      and experience of the surgeon.

PMID- 1997227
TI  - Minor anatomic abnormalities of the hip joint persisting from childhood and their
      possible relationship to idiopathic osteoarthrosis.
AB  - A retrospective review was made of roentgenograms from 30 patients with
      idiopathic osteoarthrosis of the hip. The roentgenograms were taken before the
      onset or very early in the course of the disease. Nine measurements were made on
      the anteroposterior and cross-table lateral roentgenograms. These were compared
      to 54 hips from normal patients. Twenty-nine of 30 patients had abnormal
      measurements, with as many as seven in a single individual, when compared to
      normal patients. There were no abnormalities in the control group. The
      availability of lateral views allowed an additional dimension to be added to
      previous studies in the literature. This study lends further support to the
      biomechanical theory of the etiology of idiopathic osteoarthrosis of the hip.

PMID- 1997228
TI  - Radiocolloids in the management of hemophilic arthropathy in children and
      adolescents.
AB  - Radiocolloids have been used in the treatment of hemophilic arthropathy. Fifty
      eight joints of 35 patients were injected with 2-5 mCi of yttrium-90 silicate
      under local anesthesia. A preinjection arthrogram was performed to ensure correct
      placement of the needle. Plaster of paris cast immobilization of the joint was
      used for three days. After a mean follow-up period of seven years (range, two to
      12 years), 47 joints were pain free, and 13 joints had not experienced another
      hemorrhagic episode. The mean hemorrhagic frequency had decreased from four per
      month to two per year. The radiation risk was far outweighed by the benefits of
      the procedure. Forty-seven of the 58 joints were rated as improved by the
      patients. The roentgenographic appearance of the joints had changed little. Only
      five complications occurred: three needle-track necroses because of extravasation
      of the radiocolloid, two severely painful joints immediately after injection, and
      one massive hemorrhagic episode. This form of treatment is suggested for
      hemophiliacs who have failed to respond to intensive physical and hematologic
      therapy, and for those patients who have inhibitors.

PMID- 1997229
TI  - Changing patterns in the management of fractures in children.
AB  - Advances in radiographic imagery have greatly facilitated the diagnosis and
      treatment of pediatric musculoskeletal injuries. In recent years, the indications
      for operative intervention in the treatment of children's fractures have become
      more clearly defined.

PMID- 1997230
TI  - The management of malignant bone tumors in children and adolescents.
AB  - A series of 205 pediatric patients affected by osteosarcoma, Ewing's sarcoma,
      fibrosarcoma, and malignant fibrous histiocytoma of bone were treated from 1978
      to 1988. Ninety-eight percent of the patients received chemotherapy and 63% had a
      surgical resection. Sixty-five percent of all patients were alive at 30 months
      and were considered disease free. The functional results after surgery were
      evaluated according to the Musculoskeletal Tumor Society score. In all diaphyseal
      resections and resections of the upper extremity and pelvis, the results were
      excellent or good in 60% of the cases. In resections of the proximal femur,
      distal femur, or proximal tibia and reconstruction with nonexpansible prostheses,
      the results were excellent or good in 75%. On the other hand, when arthrodeses of
      the lower extremity were used, only 14% of cases had a good result. This
      correlates with the resulting lack of articulation and serious limb shortening
      seen with progression of skeletal growth.

PMID- 1997231
TI  - Congenital anomalies of the cervical spine.
AB  - Congenital anomalies of the cervical spine are uncommon. The majority of
      afflicted individuals are asymptomatic or have only mild restriction of neck
      motion. If symptoms develop, they are usually due to cervical instability or
      degenerative osteoarthrosis. Recent information indicates that patients with
      upper cervical anomalies such as atlantooccipital fusion, anomalies of the
      odontoid, or the transverse atlantal ligament have a great propensity to develop
      early instability and neurologic problems secondary to minor traumatic events. If
      symptoms occurs in the lower cervical spine, it is usually in adult life and due
      to degenerative arthritis in the hypermobile articulations adjacent to the area
      of synostosis. The relatively good prognosis of cervical lesions is overshadowed
      by the "hidden" or unrecognized associated anomalies. There is a high incidence
      of significant scoliosis, Sprengel's deformity, renal anomalies, deafness, and
      neurologic malformations. Early recognition and treatment of these problems may
      be of substantial benefit, sparing the patient further deformity or serious
      illness.

PMID- 1997232
TI  - Osteoarthrosis retards the development of osteoporosis. Observation of the
      coexistence of osteoarthrosis and osteoporosis.
AB  - The clinical, roentgenographic, and biochemical features of the dorsal and lumbar
      spine were reviewed in 72 postmenopausal women. Nineteen women had both
      osteoporosis (vertebral collapse) and osteoarthrosis. These patients were
      compared with 26 patients who had only osteoarthrosis of the spine and 27 who had
      only vertebral collapse. The patients who had both spinal osteoporosis and
      osteoarthrosis were older, more advanced in menopause, and physically smaller in
      stature and body weight than the other groups. They also had higher serum
      parathyroid hormone level, used nonthiazide diuretics more frequently, and had
      more nulliparity than the other two groups. These patients had osteoarthrosis of
      the hip to a lesser degree than patients affected by osteoarthrosis alone, and
      they had fewer fractures of the forearm and other sites than patients with
      osteoporosis alone. The incidence of femoral neck fractures in both groups,
      however, was comparable. These results suggest that osteoarthrosis or a related
      factor might have a protective effect on the progression of osteoporosis. These
      results confirm earlier observations that postmenopausal osteoporosis and
      osteoarthrosis are two distinct diseases and not the result of normal aging.

PMID- 1997233
TI  - Analysis of 61 cases of vertebral osteomyelitis.
AB  - Sixty-one cases of bacterial vertebral osteomyelitis from July 1969 to July 1979
      were analyzed. The ages of the 49 men and 12 women ranged from 21 to 66 years.
      The portal of entry was hematogenous in 58 cases, gunshot wounds in two cases,
      and and adjacent retroperitoneal abscess in one case. Biopsy was performed in 60
      patients. There were 15 complications related to the disease. Gram-negative rods
      were the predominant bacteria isolated. Blood culture was positive in 13 of the
      26 (50%) patients tested. Eleven of the 13 (85%) organisms isolated from the
      blood cultures correlated with organisms recovered from biopsy specimens. Eleven
      of the patients had more than one disk level involved. Of the 61 patients, 29
      went on to spontaneous fusion, 17 were lost to follow-up study, 11 failed to
      fuse, three had surgical fusion, and one patient died. Recommendations for
      diagnosis included the collection of blood cultures and radionuclide bone scans.
      Management recommendations included systemic antibiotics for at least three weeks
      and immobilization with either bed rest or spinal orthoses. Surgery was indicated
      if an abscess was present, neurologic complications occurred, instability became
      a factor, or the medical treatment failed.

PMID- 1997234
TI  - Traumatic subarachnoid-pleural fistula in a child. A case report.
AB  - A seven-year-old girl sustained a gunshot wound to the chest and spine.
      Evaluation of a persistent pleural effusion demonstrated a subarachnoid-pleural
      fistula. Surgical closure of the dural defect resulted in resolution of the
      fistula. Traumatic subarachnoid-pleural fistulae are rare. The diagnosis is
      reached by an awareness of fistula formation from penetrating or blunt trauma to
      the chest.

PMID- 1997235
TI  - Influences of the protected passive mobilization interval on flexor tendon
      healing. A prospective randomized clinical study.
AB  - A prospective multicenter clinical study was carried out to determine whether
      improved tendon gliding could be achieved with greater durations of daily passive
      motion rehabilitation after flexor tendon repair. Fifty-one patients were placed
      randomly into two controlled passive-motion protocols. Group 1 patients received
      greater intervals of passive-motion rehabilitation using a continuous passive
      motion device. Group 2 patients were treated with a traditional early passive
      motion protocol for tendon rehabilitation. For Group 1 patients, the mean
      interval of controlled motion rehabilitation was 75 hours a week, and the mean
      number of cycles was 12,000. For Group 2 patients the mean interval of controlled
      passive motion was four hours a week, and the mean number of cycles was 1000. The
      minimum follow-up time was six months (mean, 10.8 months). Using Strickland and
      Glogovac's formula, the mean active motion for digits in Group 1 was 138 degrees
      +/- 6 degrees. Mean motion for tendons in Group 2 was 119 degrees +/- 8 degrees.
      The difference between Groups 1 and 2 was statistically significant. The effect
      of the number of tendons injured per digit within each group was not significant.
      The data from this experiment indicate that the duration of the daily controlled
      motion interval is a significant variable insofar as postrepair flexor tendon
      function is concerned.

PMID- 1997236
TI  - Fracture of the index metacarpal base with subluxation of the trapeziometacarpal
      joint. A case report.
AB  - A 40-year-old man fell on his outstretched arm and suffered a fracture of the
      index metacarpal base with subluxation of the thumb basal joint. The small
      fracture fragment at the base of the index metacarpal was attached to the base of
      the thumb metacarpal by a strong ligament, as noted at the time of surgery. This
      pattern of injury, a ligament-reversed Bennett's fracture, seems not to have been
      previously reported.

PMID- 1997237
TI  - Local hypothermia to prolong safe tourniquet time.
AB  - Local hypothermia was studied as a method to safely prolong tourniquet time for
      reconstructive procedures of the upper extremity. An ice blanket constructed of
      flannel cloth and cold gel packs was applied to the limb for 45 minutes
      preoperatively. Seventy-eight patients were evaluated for complications resulting
      from hypothermia and prolonged tourniquet application. The duration of continuous
      tourniquet ischemia averaged two hours and 25 minutes. Intraoperative muscle
      temperature recordings indicated that the iced limbs were an average of 12.9
      degrees cooler than noniced limbs before tourniquet inflation. Electron
      microscopic studies of biopsied muscle showed no evidence of ischemic changes.
      There were no postoperative complications associated with prolonged tourniquet
      inflation or the hypothermia blanket technique. Local hypothermia appears to be a
      safe and effective method of decreasing the adverse effects of tourniquet
      ischemia and allowing continuous tourniquet inflation time to extend safely
      beyond the customary two-hour limit.

PMID- 1997238
TI  - Inflammatory response in retrieved noncemented porous-coated implants.
AB  - One hundred forty-six noncemented porous-coated hip and knee implants retrieved
      from 97 patients were evaluated histologically for the type, amount, and anatomic
      distribution of tissue ingrowth. The degree of inflammatory cell infiltrate
      present was also evaluated and the predominant cell type was identified. An
      inflammatory infiltrate was present in the components of 21 of 97 patients (22%).
      In 16 of the 21 cases the infiltrate was lymphocytes and histiocytes with a minor
      population of plasma cells. One of the remaining five cases had a predominately
      plasma cell reaction, and the other four had significant populations of plasma
      cells. Vascular proliferation was observed in nine of the 21 cases. Bone ingrowth
      was present in ten of the 21 cases. A 38% incidence of removal for persistent
      pain was present in cases with an inflammatory infiltrate. Seventeen of 87
      patients (20%) with cobalt-chromium devices and four of ten patients (40%) with
      titanium devices were identified as having an inflammatory infiltrate. The origin
      of the inflammatory infiltrate is unclear. All patients with inflammatory
      infiltrates had noninfected implants, which were not loose roentgenographically
      or clinically at the time of removal. Hypersensitivity and allergic responses to
      metal ions may produce such infiltrates. It is impossible, however, in the
      present study to definitively determine the etiology of the infiltrates.

PMID- 1997239
TI  - Closed suction drainage following knee arthroplasty. Effectiveness and risks.
AB  - A prospective investigation was performed to determine when to remove a suction
      drain following total knee arthroplasty (TKA). Forty-one TKAs were randomly
      allocated to closed suction drainage for either 24 or 48 hours. The drain was
      removed and the tip was cut off and processed by a method giving quantitative
      cultures. In the 48-hour group, 85% of the total volume was drained during the
      first 24 hours. During the following 24-hour period, a mean volume of only 50 ml
      was drained. No organism was isolated from cultures of drain tips sampled at 24
      hours. However, at 48 hours, 25% of the drain tips yielded light growths of
      coagulase-negative staphylococci (four drain tips) and Staphylococcus aureus (one
      drain tip). Clinical evaluations of wound healing were comparable in the two
      groups. Clearly, nothing is to be gained by continuing drainage beyond 24 hours.
      If drainage is maintained for longer periods, there is an increased risk of
      contamination by bacteria.

PMID- 1997240
TI  - A test for knee posterolateral rotatory instability.
AB  - A test for knee posterolateral instability, which is a modification of the
      standard posterolateral rotatory instability test, is described. In this test,
      the patient lies supine on the examination table with hips and knees flexed to 90
      degrees. The examiner grasps both feet and attempts to maximally externally
      rotate them. A positive test is indicated by (1) excessive external rotation of
      the affected tibia, which is easily recognized since the feet act as pointers and
      amplify the external rotation, and (2) a slight posterior sag of the affected
      tibial tubercle, which is more subtle but still a very recognizable sign.

PMID- 1997241
TI  - Pes anserinus interposition in a proximal tibial physeal fracture. A case report.
AB  - A ten-year-old girl suffered a Salter-Harris Type II fracture of the proximal
      tibia. Inspection revealed interposition of the pes anserinus (PA) within the
      open physis, which prevented reduction. This may be the first case report of PA
      interposition.

PMID- 1997242
TI  - Total knee arthroplasty in patients after patellectomy.
AB  - Twenty-six total knee arthroplasties (TKAs) were evaluated in 22 patients who had
      had a patellectomy. Fourteen knees (12 patients) had a primary TKA, and 12
      patients had a revision TKA. Two patients in the revision group, whose prostheses
      failed, were from the primary TKA group. The mean follow-up time was 8.5 years in
      the primary TKA group and 7.6 years in the revision TKA group. A group of 14
      control knees with patellae was randomly generated but matched for prosthesis,
      diagnosis, surgeon, age, and time of surgery. This group was similarly evaluated
      with an average follow-up time of 6.9 years. The primary TKA group had seven
      knees that were rated as good or excellent, two as fair, and three as poor. The
      control group had a significantly higher average rating than the primary TKA
      group. In this group, there were 12 good or excellent knees, three fair, and none
      poor. Postoperative pain, flexion contracture, extension lag, and range of motion
      all contributed significant information to the final score, whereas other
      variables (walking, function, strength, and instability) did not contribute any
      additional information. Although higher overall scores may have been expected if
      the patients had patellae, the results during the follow-up examination were
      satisfactory and justified TKA in these patients. In general, however, patients
      without patellae may be at a higher risk for failure of the prosthesis, as seen
      in five patients having primary TKA and another ten patients with failed TKA
      requiring revision.

PMID- 1997243
TI  - Knee function after surgical or nonsurgical treatment of acute rupture of the
      anterior cruciate ligament: a randomized study with a long-term follow-up period.
AB  - One hundred fifty-six patients with a total rupture of the anterior cruciate
      ligament (ACL) were reexamined 41 to 80 months after injury. They were randomized
      to three treatment groups: (1) repair and augmentation of the ACL with an
      iliotibial strip, (2) repair without augmentation, and (3) nonsurgical ACL
      treatment. Associated injuries of menisci and other ligaments were treated in the
      same way for the three groups. Two-thirds of the patients in the nonsurgically
      treated group complained of instability and 17% had had a subsequent
      reconstruction of the ACL at the follow-up examination. The group treated with an
      augmented repair had a less abnormal laxity measured by a laxity-testing device.
      Sixty-three percent returned to competitive sports, as compared with 27% in the
      nonsurgical group and 32% in the only repair group. Relative strength of the
      quadriceps and hamstrings muscles were similar for all groups. The augmented
      repair group had better hop tests, reflecting a superior stability, whereas
      running was not affected by treatment but was correlated with the activity level.

PMID- 1997244
TI  - Magnetic resonance imaging for ineffectual tarsal tunnel surgical treatment.
AB  - Tarsal tunnel syndrome (TTS) is an entrapment neuropathy caused by compression of
      the posterior tibial nerve beneath the ankle flexor retinaculum. Treatment of TTS
      consists of surgical release of the retinaculum. The failure rate is 10%-20%.
      Magnetic resonance (MR) imaging was used to evaluate a patient with an
      unsatisfactory response. MR imaging demonstrated incompleteness of the surgical
      release of the flexor retinaculum.

PMID- 1997245
TI  - Fractional lengthening of the flexor tendons in clubfoot surgery.
AB  - Massive scarring of the Z-lengthened flexor digitorum and flexor hallucis longus
      is a constant finding in clubfoot surgery. A method of fractional lengthening of
      the tendons is described. This method has been proven effective in preventing
      this complication.

PMID- 1997246
TI  - The occurrence of accessory immunologic cells in bone induction.
AB  - The differentiating tissues in fracture healing and in demineralized bone-powder
      induced (DBP) bone formation were investigated with monoclonal antibodies with
      respect to the occurrence of Ia-positive cells, macrophages, and lymphocytes with
      interleukin-2 receptors (IL-2). Ia refers to molecules on the cell surface
      belonging to Class II of the major histocompatibility complex and is specific for
      the species and the individual. In both types of granulation tissues (fracture
      healing and following DBP implantation), the mesenchymal cells from the
      surrounding musculature were accompanied by large numbers of Ia-positive cells
      and common macrophages. The occurrence of IL-2 receptors was sparse in fracture
      healing but rich in DBP induction, probably because of its immunogenic
      properties, though weak. On Day 7, almost all existing cells in DBP induction
      were Ia-positive, signifying an immunologic effector phase apparently directed to
      the remaining still-passive bone powder in the periphery, while the central part
      of the inserted bone powder was producing cartilaginous cells and matrix. The
      presence of accessory immunologic cells in fracture healing is perhaps due to a
      surveillance function (a standard response on injury), but the cell
      differentiation might also be dependent on the active mediators emitted from Ia
      positive cells and macrophages. This investigation strengthens the concept that
      induced bone development occurs in experimental fracture healing.

PMID- 1997247
TI  - Experimental diabetes, insulin treatment, and femoral neck morphology and
      biomechanics in rats.
AB  - To investigate the effects of diabetes and insulin treatment on trabecular bone,
      the morphologic and biomechanical characteristics of the femoral neck in rats
      with streptozotocin-induced diabetes were studied. Young Sprague-Dawley rats were
      divided into three groups, control, diabetic (DM), and diabetic with insulin
      (DI), and maintained for ten weeks. Cantilever-bending tests to failure were
      conducted on the proximal femur, and fracture-surface cross sections were
      analyzed. Morphologically, the femoral necks in diabetic rats decreased in the
      relative size of their cortical shell and increased their trabecular core.
      Structurally, the load and the energy at the proportional limit and the total
      energy in diabetic femoral necks were significantly less than controls. In
      material properties, the diabetic femoral necks had significantly less stress at
      the proportional limit. Compared to the DM group, the DI femoral necks had
      significantly greater load and energy at the proportional limit and significantly
      greater total energy. Femoral neck mechanical and morphologic properties in
      diabetic rats were significantly lower than controls, but insulin treatment
      ameliorated diabetic osteopathy in the rat femoral neck.

PMID- 1997248
TI  - The stimulating effect of growth hormone on fracture healing is dependent on
      onset and duration of administration.
AB  - The effect of onset and duration of growth hormone administration on the
      biomechanical properties of healing rat tibial fractures was investigated after
      40 days of healing. Biosynthetic human growth hormone, 2.7 mg/kg body weight/day,
      was given in two daily injections to three groups of rats: (1) for the entire
      healing period; (2) for the first 20 days; and (3) for the last 20 days of
      healing. Three corresponding groups of control rats were injected with saline. In
      Group 1, maximum load and stiffness of the healing fractures increased to 165%
      and 175%, respectively, compared to the control group. In Group 2, maximum load,
      stiffness, maximum stress, and energy absorption at maximum load increased to
      222%, 175%, 171%, and 247%, respectively, compared to the control group. In Group
      3, no statistically detectable effects were found. The results show that growth
      hormone stimulates fracture healing both when given during the first part of the
      healing period and when given during the entire healing period.

PMID- 1997249
TI  - New Jersey low-contact-stress (LCS) knee replacement system.

PMID- 1997250
TI  - Osteogenic sarcoma. A study based on 133 patients. 1955.

PMID- 1997251
TI  - A method of assessment of the clubfoot deformity.
AB  - The literature on clubfeet is inadequate because a common method language for
      assessing the deformity is lacking. Different severities of clubfoot deformity
      will give different results for a standard procedure: a less severe deformity can
      be corrected by limited releases, whereas a severe deformity requires radical
      procedures. This paper presents a language of assessment that has been used for a
      number of years. The importance of developing a language of assessment to be able
      to identify the various types of clubfoot deformity is important if the treatment
      of this condition is to develop within the field of pediatric orthopedics.

PMID- 1997252
TI  - Neurologic status of spina bifida patients and the orthopedic surgeon.
AB  - The purpose of this paper is to review recent developments in the neurologic
      assessment of spina bifida patients. Determination of the neurosegmental level of
      the lesion, recognition of spasticity and progressive paralysis, the potential
      for deformity, and functional expectations are described. The status of the
      neurologic deficit remains the most important factor in determining the
      myelomeningocele patient's ultimate functional abilities. Accurate neurologic
      assessment will assist in meeting the aims of orthopedic management, which
      include preventing joint contracture, correcting deformity, preventing skin
      sores, and obtaining the best possible locomotor function.

PMID- 1997253
TI  - Gait analysis in the treatment of the ambulatory child with cerebral palsy.
AB  - Surgical treatment of children with cerebral palsy has changed from staged,
      single joint procedures to comprehensive simultaneous bony and soft-tissue
      corrections. This regimen of treating multiple joint levels and planes of
      abnormality is subject to error when based solely on the clinical examination. A
      more scientific evaluation can be provided by the use of clinical gait analysis.
      Both preoperative and postoperative analyses provide the clinician with
      information from which neurologic patterns can be determined and surgical
      protocols can be judged.

PMID- 1997254
TI  - The present attitude toward the biology and technology of limb lengthening.
AB  - Over the past ten years, many technical innovations and biologic concepts have
      appeared as they relate to the lengthening of long bones. Each of these has had a
      substantial influence upon the approach to the treatment of major discrepancies
      in limb length and angular deformities. It is the purpose of this paper to
      present these issues as objectively as possible so that the reader can put them
      into proper perspective, recognizing that there will be some degree of bias in
      the implementation of some of the technical devices. To appreciate the utility of
      these techniques, it is necessary to understand the biologic foundation of each
      method as well as its advantages and disadvantages.

PMID- 1997255
TI  - The management of chronic osteomyelitis.
AB  - Chronic osteomyelitis of childhood is heterogeneous but it can be broadly
      classified into nonspecific or specific groups. Children with chronic
      osteomyelitis because of mycobacteria or mycoses are included within the specific
      group. The nonspecific group is the larger. It includes chronic osteomyelitis as
      a sequel to late acute osteomyelitis as well as chronic unifocal and chronic
      multifocal osteomyelitis. Whereas Staphylococcus aureus and other pyogenic
      organisms are commonly cultured from chronic lesions following late acute
      osteomyelitis, they are less frequently cultured from those with chronic unifocal
      osteomyelitis and rarely cultured from those with chronic multifocal
      osteomyelitis. The methods of treatment and the results also differ between these
      subgroups of nonspecific osteomyelitis. Lesions following late acute
      osteomyelitis are usually cured following surgery and antibiotics. Chronic
      unifocal osteomyelitis is usually cured with antibiotics only or with surgery and
      antibiotics. In contrast, surgery and antibiotics are largely ineffective in
      children with chronic multifocal osteomyelitis, but the disease appears to be
      self-limiting.

PMID- 1997257
TI  - Abstracts of papers presented at the ninety-second Annual Meeting of the American
      Society for Clinical Pharmacology and Therapeutics. San Antonio, Texas, March 13
      15, 1991.

PMID- 1997256
TI  - A perspective on recent trends for scoliosis correction.
AB  - The basic principles for scoliosis surgery learned during the Harrington era are
      still valid today. Experience has confirmed the need for careful selection of the
      vertebrae to be instrumented, the value of anterior release for rigid curves in
      imparting convertibility of the deformity, and the importance of careful fusion
      techniques. During the last decade, further development has occurred because of
      an increased knowledge of the biomechanical needs for the internally instrumented
      spine and a three-dimensional appreciation of the scoliotic curve. Biomechanical
      advances have centered on an understanding of the load-sharing properties
      afforded by the multiple spinal purchase sites (segmental spinal instrumentation)
      and the value of two-rod systems linked by couplers. These advances have provided
      an increased stiffness of the instrumental spine, a reduction in correction loss,
      improved fatigue properties of the implant, and fewer pseudarthroses. The most
      important advance of the last decade is an improved awareness of the three
      dimensional approach to the scoliotic deformity with the need to preserve or
      improve sagittal contours. In particular, the importance of the loss of normal
      thoracic kyphosis or lumbar lordosis has been emphasized. These conceptual gains
      have led to the development of many new instrument systems to correct deformity.
      Each is associated with advantages, problems, and risks that must be understood
      to make intelligent choices for treatment.

PMID- 1997258
TI  - The case of Nancy Cruzan and ... its impact on Colorado physicians. Part I.

PMID- 1997259
TI  - AIDS incidence increases in women.

PMID- 1997260
TI  - AIDS: a special report. Colorado youth at risk.

PMID- 1997261
TI  - A Colorado leader in the battle ... against multiple sclerosis.

PMID- 1997262
TI  - Patterns of lung repair. A morphologist's view.

PMID- 1997263
TI  - Epigenetic autocrine and paracrine factors regulating lung morphogenesis. A
      paradigm for lung repair.

PMID- 1997264
TI  - Resolution of inflammation. A perspective.

PMID- 1997265
TI  - Bombesin may play a role in fetal lung growth and maturation in utero and in lung
      organ culture.

PMID- 1997266
TI  - Role of the epithelium in lung repair.

PMID- 1997267
TI  - Epithelial injury is a critical factor in the development of pulmonary fibrosis
      following multiple episodes of inflammation.

PMID- 1997268
TI  - Determination of transforming growth factor-beta mRNA levels in pulmonary
      arteries from normal and hypoxic calves.

PMID- 1997269
TI  - Connective tissue production by vascular smooth muscle in development and
      disease.

PMID- 1997270
TI  - Smooth muscle actin is expressed by air space fibroblast-like cells in idiopathic
      pulmonary fibrosis and hypersensitivity pneumonitis.

PMID- 1997271
TI  - Tropoelastin pre-mRNA is alternatively spliced at different frequencies during
      rat lung development.

PMID- 1997272
TI  - Evaluation of extracellular matrix turnover. Methods and results for normal human
      lung parenchymal elastin.

PMID- 1997273
TI  - Platelet-derived growth factor produced by pulmonary cells.

PMID- 1997274
TI  - Expression of platelet-derived growth factor A-chain (PDGF-A) mRNA in lung tissue
      and cells. Complex regulation during remodeling.

PMID- 1997275
TI  - Asbestos-induced alveolar injury. Evidence for macrophage-derived PDGF as a
      mediator of the fibrogenic response.

PMID- 1997276
TI  - Analysis of local mRNA expression for extracellular matrix proteins and growth
      factors using in situ hybridization in fibroproliferative lung disorders.

PMID- 1997277
TI  - The commonality of cutaneous wound repair and lung injury.

PMID- 1997278
TI  - Apoptosis (programmed cell death) and functional changes in aging neutrophils.
      Modulation by inflammatory mediators.

PMID- 1997279
TI  - Role of transforming growth factor-beta in repair and fibrosis.

PMID- 1997280
TI  - Enhanced expression and immunohistochemical distribution of transforming growth
      factor-beta in idiopathic pulmonary fibrosis.

PMID- 1997281
TI  - Regulation of lung collagen production during wound healing.

PMID- 1997282
TI  - Molecular interactions of isolated rat type II pneumocytes with components of
      extracellular matrices in vitro.

PMID- 1997283
TI  - Collagen synthesis and degradation by systemic sclerosis lung fibroblasts.
      Responses to transforming growth factor-beta.

PMID- 1997284
TI  - Mononuclear cell-fibroblast interactions in the human lung.

PMID- 1997285
TI  - Induction of transcription and secretion of TGF-alpha by activated human
      monocytes.

PMID- 1997286
TI  - Fibroproliferative disorders.

PMID- 1997287
TI  - Mechanisms of transforming growth factor-beta-induced collagen formation by human
      lung fibroblasts.

PMID- 1997288
TI  - Idiopathic pulmonary fibrosis. A paradigm for lung injury and repair.

PMID- 1997289
TI  - Human macrophages secrete platelet-activating factor acetylhydrolase. A mechanism
      for resolution of pulmonary inflammation.

PMID- 1997290
TI  - How children tell: the process of disclosure in child sexual abuse.
AB  - In an analysis of the disclosure by a large number of children from three to 17
      years of age of having been sexually abused, and who were eventually confirmed as
      credible victims, the large majority at first denied the abuse. The authors
      describe disclosure as a process with definable phases and characteristics-
      seldom the single entity that typical investigations consider disclosure to be,
      thereby setting the stage for ensuring injustices and harm to the children.

PMID- 1997291
TI  - Factors associated with foster care length of stay.
AB  - Within foster care service agencies the accurate estimate of children's length of
      stay in foster care has important implications for both planning and implementing
      services. Yet information on factors associated with length of stay is
      incomplete. This article reviews what is presently known and presents new data in
      a cohort of Maryland children.

PMID- 1997292
TI  - Therapeutic management of preschool cases of alleged but unsubstantiated sexual
      abuse.
AB  - Alleged sexual abuse among preschoolers is often difficult to substantiate, and
      is rarely criminally prosecuted. Yet very young children are vulnerable when
      abuse is suspected but cannot be proven. These cases call for a special form of
      structured therapeutic management that seeks to inhibit the possibility of abuse
      while buying time for these very young children so that potential later abuse can
      be reported more accurately.

PMID- 1997293
TI  - A supervised independent-living orientation program for adolescents.
AB  - A program is described that provides for transition into a relatively
      unstructured supervised independent-living program for adolescents with a history
      of behavioral and emotional disturbance, often including delinquency and/or
      psychiatric hospitalization. Contracts used to define expectations, logistics,
      and conflicts experienced by the youths are discussed. Developmental issues are
      highlighted, focusing on the rapprochement subphase.

PMID- 1997294
TI  - Bronchial asthma.
AB  - Asthma is one of the most common respiratory problems in modern industrialized
      countries, affecting over 5% of the population. It affects all age groups from
      infants to senior citizens, and mortality rates from asthma appear to be
      increasing during the past few years in the United States as well as in other
      industrialized countries. Asthma tends to occur in families, associated with
      other allergic disease, and may be induced by a wide variety of environmental
      antigens, most commonly inhaled allergens such as pollen and dust. Bronchial
      challenge with a specific allergen results in an early bronchospastic response
      with a relatively brief duration, and in a significant number of patients there
      is a late response with onset after 3 to 4 hours, lasting hours to days. This
      late response is associated with a bronchial hypersensitivity reaction, which is
      demonstrable by nonspecific challenge testing in the laboratory. During the
      period of bronchial hyperresponsiveness patients are prone to develop attacks
      following exposure to a wide variety of "triggers," including cold air, fumes, or
      cigarette smoke. The current approach to management of patients with asthma
      emphasizes prevention, with avoidance of specific allergens when possible, and
      chronic use of anti-inflammatory agents including corticosteroids and cromolyn
      sodium. The goal is to decrease the bronchial hyperresponsiveness. Management of
      the acute asthma attack consists of bronchodilator therapy, primarily with
      inhaled beta-adrenergic agonists, and administration of oral or systemic
      corticosteroids if the attack is not rapidly relieved. Additional therapeutic
      agents including theophylline and anticholinergics may be useful in some
      situations. Response to therapy during the first couple of hours in the emergency
      room is the most important predictor of the course of the acute attack, and
      patients who have not responded significantly after 2 hours of maximum therapy
      are candidates for hospital admission or prolonged emergency room observation.
      The goal of acute therapy is to wean the patient from intravenous drugs and place
      him or her on rapidly tapering doses of oral prednisone while initiating a
      vigorous program of preventive therapy. Follow-up observation, both in the office
      and in the patient's home, is vital and involves extensive patient education and
      objective testing of peak airflow. In general, the course of asthma is relatively
      benign compared with other obstructive airway diseases; however, significant
      mortality exists, especially in older patients and those with late-onset asthma.

PMID- 1997295
TI  - [Prolongation of hospital stay by nosocomial pneumonia and wound infection].
AB  - From June 1988 to September 1989, a prospective survey comprising a total of 1183
      patients in a university hospital was carried out to ascertain the additional
      length of stay in intensive care units because of nosocomial pneumonia associated
      with artificial ventilation (418 patients, 296 men, 122 women, mean age 48.8 +/-
      21 years, ventilated for more than 24 h) or by postoperative wound infections
      (765 patients, 501 men, 264 women, mean age 60 +/- 11 years, after operations on
      the large bowel, heart or biliary tract). Each patient with a nosocomial
      infection was matched against a variable number of control patients (for cases of
      pneumonia a maximum of 6, for wound infections a maximum of 10) without
      nosocomial infection. Pneumonia developed in 100 (23.9%) of artificially
      ventilated patients, and 46 of these patients together with 101 controls were
      entered into the matching procedure. 24 patients with pneumonia had to be
      excluded from analysis because no controls could be found for them, and also 30
      patients who died while in the intensive care unit. 49 (6.4%) of the surgical
      patients contracted postoperative wound infections. 43 of them, together with 210
      controls, were entered into the matching procedure. Among patients with pneumonia
      the average additional duration of stay was 11.5 days, and among patients with
      post-operative wound infections it was 13.9 days. The results confirm that
      nosocomial infections contribute substantially to prolongation of hospital stay
      and hence to the costs.

PMID- 1997296
TI  - [Chronic thromboembolic cor pulmonale in pacemaker-associated right atrial
      thrombi. Pulmonary thromboendarterectomy with removal of the electrodes as a life
      saving measure].
AB  - Life-threatening chronic cor pulmonale occurred in a 22-year-old woman with
      congenital 3 degrees atrioventricular block, 6 years after implantation of a
      pacemaker and 3 1/2 years after removal of the pacemaker (the electrodes were too
      firmly attached to be removed). The emboli originated from the right-atrial
      thrombi which had formed around the electrodes left in situ. The embolic source
      shrank during systemic administration of urokinase, initially 600,000 IU in 60
      min, then 100,000 IU per hour, and pulmonary perfusion improved transiently.
      Nonetheless the patient became breathless on the slightest physical exertion.
      Recurrent syncopal attacks with marked increase of pulmonary artery pressure
      necessitated pulmonary thrombendarterectomy and removal of the electrode and
      wires. Thereupon the patient's condition clearly improved so that 6 months
      postoperatively her exercise tolerance was again unimpaired.

PMID- 1997297
TI  - [Therapy of motility disorders of the stomach and small intestine].

PMID- 1997298
TI  - [Indications for percutaneous transluminal coronary angioplasty].

PMID- 1997299
TI  - [No adjustment of chief physician's fees in the hospital ward area because of the
      new change of the Hospital Law of 1/1/1985. Decision of the Federal Labor Court
      of 7/25/1990].

PMID- 1997300
TI  - [Blood sugar determination].

PMID- 1997301
TI  - [Serum ferritin and hemochromatosis].

PMID- 1997302
TI  - [Neuritis of the optic nerve].

PMID- 1997303
TI  - [Pacemaker therapy in sleep apnea syndrome].

PMID- 1997304
TI  - [Incidence of hepatitis B in residents of homes for mentally retarded].

PMID- 1997305
TI  - [Intolerance reactions to ionic and nonionic contrast media in cardiac diagnosis.
      A randomized double-blind study].
AB  - Reactions to an ionic and a nonionic contrast medium were compared in a
      randomized double-blind trial involving 1153 patients (897 men, 256 women; mean
      age 56 [18-84] years) who underwent left-heart catheterization with coronary
      angiography. 584 patients (group 1) received the ionic contrast medium meglumine
      diatrizoate (Urografin 76%), while 569 (group 2) received the nonionic iopromide
      (Ultravist -370). Reactions of skin and mucosae, heart and circulation, lungs and
      respiratory tract, as well as of the central nervous system were noted. There was
      no significant difference between the two groups with respect to age, weight,
      height, allergic predisposition, left-ventricular ejection fraction, or serum
      electrolyte concentrations. Mild reactions, not requiring any treatment, occurred
      in 108 of the 1153 patients (9.4%), 85 (14.6%) in group 1 and 23 (4%) in group 2
      (P less than 0.001). Severe reaction requiring treatment occurred in eight
      patients of group 1 (1.4%) and 14 of group 2 (2.5%)--difference not significant.
      Ventricular fibrillation was more frequent among group 2 patients (four compared
      with one in group 1), while two of three asystoles requiring treatment occurred
      in group 1 patients. The results show that, while mild reactions not requiring
      treatment were clearly less frequent after nonionic contrast medium injection,
      the risk of severe reactions was not reduced by their use.

PMID- 1997306
TI  - [The results after prosthetic aortic valve replacement. What effect does old age
      have?].
AB  - Data were retrospectively analysed of 149 consecutive patients with aortic valve
      stenosis (91 males and 58 females; mean age 64 [27-86] years) who had a
      prosthetic valve implanted between 1986 and 1988. The overall operative mortality
      rate was 3.4%, the one-year mortality rate was 4.7%. Operative mortality rate for
      those aged 27-74 years was 1.7% (2 of 120), but 10.3% (3 of 29) for those aged 75
      to 86 years (P less than 0.05). None of the patients in clinical grade III (NYHA
      classification) died within 30 days of the operation. Among those in grade IV the
      operative mortality rate was 15.8% (3 of 19) for those aged 75-86, but 4.0% (2 of
      50) for those aged below 75 years (P less than 0.05). Valve replacement in
      symptomatic aortic stenosis with a prosthetic valve is today the method of
      choice. Operative mortality rate is low, even for patients of advanced age,
      particularly if the operation is done early.

PMID- 1997307
TI  - [Liver abscesses due to Yersinia enterocolitica].
AB  - A 41-year-old man with type II diabetes for the past five years had for three
      weeks been suffering from high fever (up to 40 degrees), feeling of pressure in
      the upper abdomen, loss of weight, lack of appetite and increasing weakness.
      Ultrasound examination as an out-patient was suspicious of diffuse liver
      metastases from an unknown primary tumour. Ultrasonography and computed
      tomography after hospitalization suggested multiple liver abscesses. Fine-needle
      biopsy grew Yersinia enterocolitica. In addition, there was evidence of an
      asymptomatic intestinal Yersinia infection without septicaemia. After intravenous
      treatment with three times daily 5 g mezlocillin and three times daily 80 mg
      tobramycin the fever at first subsided, but the liver abscesses remained
      unchanged. When fever recurred a week later, cefotaxim, three times daily 2 g,
      was started. This led to complete regression of the abscesses within three weeks,
      and the patient has been free of symptoms since.

PMID- 1997308
TI  - [Xanthomas of the Achilles tendon as the cardinal symptom of sitolsterolemia].
AB  - The circumference of both Achilles tendons had gradually increased over the years
      in a now 32-year-old man (diameter of the left tendon 4.5 cm, of the right one
      3.5 cm). This finally led to exercise-related pain in both tendons. Biopsy
      revealed benign deposition of xanthomata. Serum total cholesterol concentration
      was 261 mg/dl. Determination of various sitosterol fragments in serum gave a beta
      sitosterol level of 43 mg/dl (normal range 0.3-1.7 mg/dl), characteristic of
      sitosterolaemia, which is an autosomal recessive disease causing intestinal
      hyperabsorption of a range of plant steroids closely related to cholesterol. On a
      diet low in plant steroids and treatment with cholestyramine (up to 32 g daily)
      the beta-sitosterol concentration fell, but only to 35 mg/dl, because of poor
      patient compliance. The patient died suddenly from coronary artery stenosis seven
      months after the diagnosis of sitosterolaemia.

PMID- 1997309
TI  - [Chologenic diarrhea. Its etiology, symptoms and diagnosis].

PMID- 1997310
TI  - [Atypical forms of AIDS-associated Pneumocystis carinii infection].

PMID- 1997311
TI  - [The listing of physicians in directories. The judgement of the Munich Higher
      Regional Court of 21 December 1989].

PMID- 1997312
TI  - [Anxiety before gastrointestinal endoscopy].

PMID- 1997313
TI  - [Compliance in malaria prophylaxis with chloroquine and proguanil].

PMID- 1997314
TI  - [The retrogression of atherosclerotic coronary stenoses after a change in life
      style].

PMID- 1997315
TI  - [Ursodeoxycholic acid and extracorporeal shockwave lithotripsy].

PMID- 1997316
TI  - Sensory transduction in eukaryotes. A comparison between Dictyostelium and
      vertebrate cells.
AB  - The organization of multicellular organisms depends on cell-cell communication.
      The signal molecules are often soluble components in the extracellular fluid, but
      also include odors and light. A large array of surface receptors is involved in
      the detection of these signals. Signals are then transduced across the plasma
      membrane so that enzymes at the inner face of the membrane are activated,
      producing second messengers, which by a complex network of interactions activate
      target proteins or genes. Vertebrate cells have been used to study hormone and
      neurotransmitter action, vision, the regulation of cell growth and
      differentiation. Sensory transduction in lower eukaryotes is predominantly used
      for other functions, notably cell attraction for mating and food seeking. By
      comparing sensory transduction in lower and higher eukaryotes general principles
      may be recognized that are found in all organisms and deviations that are present
      in specialised systems. This may also help to understand the differences between
      cell types within one organism and the importance of a particular pathway that
      may or may not be general. In a practical sense, microorganisms have the
      advantage of their easy genetic manipulation, which is especially advantageous
      for the identification of the function of large families of signal transducing
      components.

PMID- 1997317
TI  - Inhibition of protein synthesis by antagonists of calmodulin in Ehrlich ascites
      tumor cells.
AB  - Several recent publications indicate that Ca2+ is required for protein synthesis
      in mammalian cells, including the Ehrlich ascites tumor cell. The present
      communication examines whether the effects of Ca2+ might be mediated through
      calmodulin or a related protein. Four calmodulin antagonists belonging to
      different chemical categories were used to provide evidence of calmodulin
      involvement. Three of the antagonists inhibited protein synthesis in intact
      cells; 50% inhibitory concentrations were 10 microM calmidazolium, 12 microM N-(6
      aminohexyl)-5-chloro-1-naphthalenesulfonamide (W7) and 17.5 microM
      trifluoperazine (TFP). Initiation was preferentially inhibited as indicated by an
      increase in the 80S monomers accompanied by a significant disaggregation of
      polyribosomes. All the antagonists also inhibited protein synthesis initiation in
      the cell-free protein-synthesizing system; 50% inhibitory concentrations for
      compound 48/80, calmidazolium, TFP, and W7 were 10 microM, 125 microM, 300 microM
      and 500 microM, respectively. A weak analogue of W7 inhibited only 20% at 1000
      microM. Inhibition in the cell-free system was reversed by the addition of
      exogenous calmodulin in all four cases. The levels of 43S complexes were
      significantly elevated with all four antagonists, indicating a block in the
      utilization of 43S complexes. The similarity of the effects of four distinct
      classes of antagonists and their ready reversal by exogenous calmodulin leads us
      to suggest that there may be a role for calmodulin or a very similar calcium
      binding protein in protein synthesis.

PMID- 1997318
TI  - Amino acid and cDNA sequences of a methionine-rich 2S protein from sunflower seed
      (Helianthus annuus L.).
AB  - The amino acid sequence of a methionine-rich 2S seed protein from sunflower
      (Helianthus annuus L.) and the sequence of a cDNA clone which codes for the
      entire primary translation product have been determined. The mature protein
      consists of a single polypeptide chain of 103 amino acids (molecular mass 12133
      Da) which contains 16 residues of methionine and 8 residues of cysteine. The cDNA
      sequence established that the protein is synthesized as a precursor of 141
      residues with a typical hydrophobic signal sequence of 25 residues followed by a
      further 13-residue hydrophobic pro-sequence which is presumably removed by post
      translational cleavage. The sequence of the mature protein and that deduced from
      the cDNA were identical with no evidence of processing at the C-terminus.
      Comparison of the sunflower methionine-rich protein sequence with sequences of
      other seed 2S proteins from dicotyledons and monocotyledons showed limited but
      distinct sequence similarities; in particular the arrangement of the cysteine
      residues was conserved. The sunflower protein shows 34% identity with the
      methionine-rich Brazil nut 2S protein and the prepro regions of the precursors of
      these two proteins show about 50% identity. This similarity indicates that these
      methionine-rich 2S proteins have diverged as a subclass of the 2S superfamily of
      proteins which contain only 2-3% methionine. While the related 2S proteins from
      other dicotyledons are processed to a small and large subunit, the sunflower
      protein is not cleaved in this way.

PMID- 1997319
TI  - Conformational change of turkey-gizzard caldesmon induced by specific chemical
      modification with carbodiimide.
AB  - Water soluble 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide was used to
      internally cross-link carboxyl and lysyl groups of caldesmon. The modification
      did not involve the two cysteines of the molecule which were previously labelled
      with N-iodoacetyl-N'-(5-sulfo-1-naphthyl)ethylenediamine. The modified caldesmon
      exhibited a smaller Stokes radius (4.0 nm instead of 6.3 nm) and its
      electrophoretic mobility corresponded to an apparent molecular mass of
      approximately 82 kDa, appreciably lower than that of the native molecule (120
      kDa), but more similar to the reported true molecular mass of 86,974 Da of
      chicken-gizzard caldesmon (Bryan, J., Imai, M., Lee, R., Moore, P., Cook. R. G. &
      Lin, W. (1989) J. Biol. Chem. 264, 13,873-13,879). Comparative circular dichroism
      analysis indicated a decrease of the alpha-helix content from 43% to 36%
      resulting from the chemical modification. The 1H-NMR spectra of the native and
      modified caldesmon showed that the covalent cross-linking affected mainly the
      central and N-terminal parts of the molecule. The C-terminal part, rich in
      aromatic amino acids, was unmodified by the carbodiimide treatment. This was also
      corroborated by the continued ability of the modified caldesmon to bind to actin
      and calmodulin, and by the property of the 90-kDa proteolytic N-terminal fragment
      to give an internally cross-linked species of 60 kDa. Using electron microscopy,
      the modified protein was shown to have a more compact shape and a reduced
      capacity to induce tight and long F-actin bundles. These conformational changes
      were obtained when the carbodiimide reaction was conducted at pH 6.0 and were not
      observed at pH 8.0. This suggests that local variation of the pH might affect the
      conformation of caldesmon which changes from an elongated to more compact shape,
      stabilized by electrostatic interactions. It is proposed that the flexibility of
      caldesmon might be involved in the regulatory function of this protein in the
      smooth muscle and might favour tightly packed F-actin bundles or weaker
      interactions between actin filaments.

PMID- 1997320
TI  - Isolation and structure elucidation of a novel adipokinetic hormone (Lom-AKH-III)
      from the glandular lobes of the corpus cardiacum of the migratory locust, Locusta
      migratoria.
AB  - A new adipokinetic hormone (named Lom-AKH-III) was isolated from the glandular
      lobes of the corpora cardiaca of Locusta migratoria. At the N-terminus it is
      blocked by a 5-oxoproline (pyroglutamic acid) residue (less than Glu). After
      enzymatic deblocking, the amino acid sequence of the N-terminus was partly
      established by automatic Edman degradation to be [less than Glu]-Leu-Asn-Phe-Thr
      Pro-. Fast-atom-bombardment spectrometry (FAB-MS) revealed that the new hormone
      is an octapeptide, which is amidated at the C-terminus, and has a relative
      molecular mass of 1072. Based on the FAB-MS data the complete sequence is less
      than Glu-Leu-Asn-Phe-Thr-Pro-Trp-Trp-NH2, which was confirmed by chemical
      synthesis. All characteristics from HPLC, FAB-MS and biological activity of the
      natural hormone and the synthetic peptide appeared to be identical. Although the
      structure of this new hormone resembles that of Lom-AKH-I (less than Glu-Leu-Asn
      Phe-Thr-Pro-Asn-Trp-Gly-Thr-NH2), its amino acid sequence points to a completely
      different route for its biosynthesis, involving a third prohormone. High-[K+]
      containing media can cause release of all three adipokinetic hormones in vitro.
      Interestingly, the new hormone is absent in another locust species. Schistocerca
      gregaria. Based on in vitro biosynthesis experiments the turnover for this
      hormone is very high, suggesting an important physiological function. Locusta
      migratoria is the first insect species in which three different adipokinetic
      hormones have been demonstrated.

PMID- 1997321
TI  - cDNA sequence and deduced amino acid sequence of the precursor of the 37-kDa
      inner envelope membrane polypeptide from spinach chloroplasts. Its transit
      peptide contains an amphiphilic alpha-helix as the only detectable structural
      element.
AB  - We present the nucleotide sequence and the deduced amino acid sequence of a cDNA
      clone that encodes the entire precursor of the 37-kDa inner envelope membrane
      protein from spinach chloroplasts. The precursor protein consists of 344 amino
      acids (Mr 38,976). In vitro processing followed by radiosequence analysis of the
      in vitro transcribed and translated precursor protein revealed that its transit
      peptide consists of only 21 amino acid residues. The transit peptide has the
      potential to form an amphiphilic alpha-helix with a strong hydrophobic moment. It
      is speculated that this structural element represents an ancestral envelope
      targeting domain. The in vitro synthesized precursor protein is directed to the
      chloroplasts and it is inserted into the envelope membrane in an ATP-dependent
      manner. The mature protein (323 amino acid residues, Mr 36,830) has a moderate
      hydrophobicity and contains only one membrane-spanning segment which is located
      at the C-terminus and possibly anchors the protein within the envelope membrane.

PMID- 1997322
TI  - Purification and properties of an aryl-alcohol dehydrogenase from the white-rot
      fungus Phanerochaete chrysosporium.
AB  - An intracellular aryl-alcohol dehydrogenase (previously referred to as aryl
      aldehyde reductase) was purified from the white-rot fungus Phanerochaete
      chrysosporium. The enzyme reduced veratraldehyde to veratryl alcohol using NADPH
      as a cofactor. Other aromatic benzaldehydes were also reduced, but not aromatic
      ketones. Methoxy-substituted rings were better substrates than hydroxylated ones.
      The enzyme was also able to reduce a dimeric aldehyde (4-benzyloxy-3
      methoxybenzaldehyde). The highest reduction rate was measured when 3,5
      dimethoxybenzaldehyde was used as a substrate. On SDS/PAGE the purified enzyme
      showed one major band with a molecular mass of 47 kDa, whereas gel filtration
      suggested a molecular mass of 280 kDa. Polyclonal antibodies raised against the
      gel purified 47-kDa protein were able to immunoprecipitate the aryl-alcohol
      dehydrogenase indicating that its activity possibly resides entirely in this
      protein fragment. The pI of the enzyme was 5.2 and it was most active at pH 6.1.
      The aryl-alcohol dehydrogenase was partially inhibited by typical oxidoreductase
      inhibitors.

PMID- 1997323
TI  - Carbohydrate microheterogeneity of rat serotransferrin. Determination of glycan
      primary structures and characterization of a new type of trisialylated
      diantennary glycan.
AB  - A previously established procedure [Regoeczi, E., Chindemi, P.A., Rudolph, J. R.,
      Spik, G. & Montreuil, J. (1987) Biochem. Cell Biol. 65, 948-954] was used to
      isolate from three DEAE-cellulose chromatographic fractions of diferric rat
      serotransferrin (rTf) subpopulations having discernible affinities for
      concanavalin A (ConA). These entities are designated rTf-1 (not retarded by ConA
      column), rTf-2 (retarded) and rTf-3 (bound). Each rTf type was found to be
      endowed with carbohydrate sufficient to account for a single diantennary
      glycan/protein molecule. Glycan structures were determined on the glycopeptides
      by employing GLC/MS and 400-MHz 1H-NMR spectroscopy. All glycans possessed a
      common, trimannosyl-N,N'-diacetylchitobiose core with or without one L-fucose
      alpha-1,6-linked to the Asn-linked GlcNAc. However, there were differences in the
      antennae. Thus, in rTf-3, both antennae were of the disialylated diantennary N
      acetyllactosamine type which is frequently encountered in other plasma
      glycoproteins. However, the alpha-1,3-Man-linked antenna in rTf-1 as well as rTf
      2 had the sequence: Neu5Ac(alpha 2-3)Gal(beta 1-3)[Neu5Ac(alpha 2-6)]GlcNAc(beta
      1-2)Man. In addition, the alpha-1,6-Man-linked antenna deviated in rTf-2 from the
      standard structure by having the sequence: Neu5Ac(alpha 2-3)Gal(beta 1
      3)GlcNAc(beta 1-2)Man. The possible relevance of the above structures to the ConA
      binding of rTf is discussed. A further preparation, obtained from the most
      anionic DEAE-cellulose fraction (peak V) or rTf contained several tetrasialylated
      diantennary glycans whose precise structures remain to be established in future
      studies.

PMID- 1997324
TI  - Secondary structure and orientation of the amphipathic peptide GALA in lipid
      structures. An infrared-spectroscopic approach.
AB  - GALA, a synthetic, amphipathic 30-amino-acid peptide, based upon a Glu-Ala-Leu
      Ala motive, was designed to mimic the behavior of viral fusion proteins. GALA is
      a water-soluble peptide with an aperiodic conformation at neutral pH, and becomes
      an amphipathic alpha helix as the pH is lowered to 5, where it interacts with
      phospholipid bilayers. Attenuated total-reflection infrared spectroscopy, using
      polarized light, provides information on the structure and orientation of the
      peptide and the lipids, which is not subject to artifacts due to light scattering
      with large particles. H/2H-exchange rate of the amide N-H group and analysis of
      the shape of the amide I' by Fourier self-deconvolution and curve fitting
      indicate that the alpha-helical content increases from 19% to 69%, on lowering
      the pH. A further increase to 100% alpha helix is observed after interaction with
      palmitoyloleoylglycerophosphocholine (PamOleGroPCho) vesicles. Dichroism data
      obtained with oriented bilayers of the PamOleGroPCho-GALA complex demonstrate
      that PamOleGroPCho hydrocarbon chains and the peptide alpha helical axis are
      essentially perpendicular (+/- 15) to the membrane plane. At neutral pH, in the
      presence of dimyristoylglycerophosphocholine (Myr2GroPCho), GALA is known to form
      discoidal structures similar to those formed under the same conditions by
      apolipoproteins AI and AII. In these discoidal complexes, the alpha-helical
      content was estimated to be 65%, with the rest of the structure being essentially
      unordered. No significant modification of the all-trans conformation of the
      hydrocarbon chain of Myr2GroPCho was detected upon disc formation. Dichroism
      measurements show that the alpha-helical axis is essentially parallel to the
      hydrocarbon chains. These data support a model in which a discoidal patch of the
      bilayer is surrounded by amphipathic helices which shield the hydrophobic region
      of the bilayer from the aqueous environment. The infrared spectrum of GALA in
      this complex was found to be very similar to those of apolipoproteins AI and AII
      which form discoidal complexes with Myr2GroPCho, but the spectrum is quite
      different from that of apolipoprotein B100 in low-density lipoproteins, which
      does not form discoidal complexes.

PMID- 1997325
TI  - Oxygen tension does not affect urea synthesis in perifused rat hepatocytes.
AB  - Perfusion of rat liver had led to the suggestion that oxygen tension, rather than
      the distribution of enzymes of urea synthesis, plays a key role in the regulation
      of urea synthesis in the periportal and pericentral areas of the liver lobule [F.
      W. Kari, H. Yoshihara and R. G. Thurman (1987) Eur. J. Biochem. 163, 1-7]. We
      have directly tested the effect of oxygen concentration on ureogenesis under
      steady-state conditions in isolated hepatocytes perifused with physiological
      concentrations of ammonia. We found that ureogenesis is independent of the oxygen
      concentration. Only at oxygen concentrations below 25 microM (which is below the
      oxygen concentration in liver) was urea synthesis decreased. This was because
      insufficient production of ATP led to decreased flux through carbamoyl-phosphate
      synthase. It is concluded that oxygen does not control urea synthesis.

PMID- 1997326
TI  - Structures and characterization of sex-specific mouse cytochrome P-450 genes as
      members within a large family. Duplication boundary and evolution.
AB  - We characterized two female-specific testosterone 16 alpha-hydroxylase mouse
      cytochrome P-450 genes, 16 alpha oh-a and 16 alpha oh-b. Gene 16 alpha oh-a,
      consisting of nine exons, is approximately 38 kbp in size. The exon sequence of
      this P-450 gene is identical to cDNA pf26 nucleotide sequence [Noshiro, M.,
      Lakso, M., Kawajiri, K. & Negishi, M. (1988) Biochemistry 27, 6434-6443], which
      encodes female-specific testosterone 16 alpha-hydroxylase regulated by the murine
      Rip locus. Gene 16 alpha oh-b, containing nine exons with the same junctions as
      the 16 alpha oh-a, spans at least 20 kbp, and encodes a cytochrome P-450 whose
      deduced amino acid sequence is 90% similar to the hydroxylase. Nucleotide
      sequences revealed that duplication of the two genes occurred 4-22 million years
      ago, and that the 5' duplication boundary is located 1336 bp upstream from the
      putative transcription-start site. In the flanking regions of both genes, there
      is a long stretch (100 bp) of CA repeats in addition to other motifs, including
      TATA box, glucocorticoid-response-element-core and Simian-virus-40-enhancer
      sequences and IgG light-chain gene promoter. We isolated many genomic DNA clones
      which contain exon 1 sequences, and compared their restriction maps, cross
      hybridization and nucleotide sequences. The results indicate that these genomic
      clones represent closely related genes in the 16 alpha oh family with a minimum
      of 16 members, which is further divided into classes a, b and c. 16 alpha oh-a
      and 16 alpha oh-b belong to the first and second classes, respectively. Moreover,
      extensive segmental gene conversion and nonreciprocal recombination were noted
      among the genes, particularly among those in class b. All genes in that class
      contain the long ATTT repeat sequences in intron 1, which may have triggered a
      rapid gene conversion and/or stabilize the duplicated genes.

PMID- 1997327
TI  - Determination of the covalent structure of an N- and C-terminally blocked
      glycoprotein from endocuticle of Locusta migratoria. Combined use of plasma
      desorption mass spectrometry and Edman degradation to study post-translationally
      modified proteins.
AB  - The complete structure of protein isolated from endocuticle of sexually mature
      locusts, Locusta migratoria, has been determined by a combination of automatic
      Edman degradation and plasma desorption mass spectrometry. The protein is
      extensively post-translationally modified. The N-terminal is 5-oxoproline
      (pyroglutamic acid) and the C-terminal proline residue is amidated. Furthermore,
      the protein is glycosylated by a single N-acetyl-galactosamine residue at one,
      two or three threonines. The N-terminal sequence was obtained by analysing the N
      acetylated N,O-permethylated derivative using plasma desorption mass
      spectrometry. The position and type of carbohydrate were determined by combining
      an HPLC-based carbohydrate analysis with the peak pattern of the
      phenylthiohydantoin derivative in automatic sequencing and with mass information
      on peptides. The protein has pronounced similarity to cuticular proteins from
      larvae of diptera and lepidoptera, but only slight resemblance to the previously
      sequenced locust exocuticular proteins. This indicates a similarity between soft
      larval cuticles and locust endocuticle, a similarity which may extend to their
      mechanical properties.

PMID- 1997328
TI  - Structural requirements for the binding of the pituitary adenylate-cyclase
      activating peptide to receptors and adenylate-cyclase activation in pancreatic
      and neuronal membranes.
AB  - PACAP (pituitary adenylate-cyclase-activating peptide)-binding receptors were
      investigated in membranes from the rat pancreatic acinar cell line, AR 4-2J, the
      rat hippocampus and the human neuroblastoma cell line NB-OK, by 125I-PACAP(1-27)
      (amino acid residues 1-27 of N-terminal amidated PACAP) binding and adenylate
      cyclase activation. The relative binding of 125I-PACAP(1-27) to the receptor, and
      ability to activate adenylate cyclase were PACAP greater than or equal to PACAP(1
      27) greater than PACAP(2-38) greater than PACAP(1-9)-VIP(10-28)(PACAP-VIP)
      greater than PACAP(2-27) greater than [Ser9,Tyr13]VIP greater than [Tyr13]VIP
      greater than or equal to [Ser9]VIP greater than or equal to VIP(1-23)-PACAP(24
      27)(VIP-PACAP) greater than VIP (vasoactive intestinal peptide). The N-terminal
      moiety of PACAP(1-27) was more important than the three amino acids at the C
      terminus for 125I-PACAP(1-27)-binding site recognition. For rat pancreatic 125I
      VIP-binding sites tested with 125I-VIP, the order of binding affinity was PACAP =
      PACAP(1-27) greater than or equal to VIP = [Ser9]VIP = [Tyr13]VIP =
      [Ser9,Try13]VIP greater than or equal to PACAP-VIP greater than or equal to VIP
      PACAP greater than PACAP(2-38) = PACAP(2-27). Pancreatic 125I-VIP-binding sites,
      when compared to 125I-PACAP(1-27)-binding sites, showed little specificity and
      only weak coupling, so that PACAP and VIP-PACAP acted only as partial VIP
      agonists on adenylate cyclase.

PMID- 1997329
TI  - Caldesmon-induced polymerization of actin from profilactin.
AB  - We have investigated the effect of caldesmon, a Ca2+/calmodulin-regulated actin
      binding protein, on the complex between profilin and G-actin (profilactin). We
      found that smooth muscle caldesmon dissociates this complex rapidly and induces
      the polymerization of the released actin. Native profilactin (e.g. the complex
      isolated from calf thymus) proved more resistant to the attack of caldesmon than
      a heterologous complex reconstituted from calf thymus profilin and skeletal
      muscle actin. The mode of caldesmon-induced profilactin dissociation was similar
      to that described for Mg2+, and 2 mM MgCl2 potentiated the caldesmon effect.
      Since both caldesmon and profilin have been found enriched in ruffling membranes
      of animal cells, our in vitro findings may be relevant to the regulation of actin
      filaments in living cells.

PMID- 1997330
TI  - Annual meeting of the Deutsche Gesellschaft fur Zellbiologie. Gottingen, 3-8
      March 1991. Abstracts.

PMID- 1997331
TI  - Management requires more than leadership.

PMID- 1997332
TI  - Surviving tough times.

PMID- 1997333
TI  - Developing administrative standards for nursing service.

PMID- 1997334
TI  - Nurse manager leadership impacts R.N. job satisfaction.

PMID- 1997335
TI  - Empowering others benefits all.

PMID- 1997336
TI  - Hiring recovering nurses.

PMID- 1997337
TI  - Avoiding sexism in language: when the man is really a woman.

PMID- 1997338
TI  - Nurse administrators' behaviors as related to successful middle nurse managers
      based on strategic choice theory.

PMID- 1997339
TI  - Quality of life in college students' end stage renal disease (ESRD).

PMID- 1997340
TI  - Interdependence is greater than independence.

PMID- 1997341
TI  - Living the adventure: military nursing.

PMID- 1997342
TI  - 48 days in Saudi Arabia: the story of Air Force flight nurse Dona Iversen.
      Interview by Deirdre Kruase.

PMID- 1997343
TI  - Is chemical dependency an ethical issue in nursing?

PMID- 1997345
TI  - Temporomandibular disorders and orofacial pain.

PMID- 1997344
TI  - Re-employment rights of reservists called to active duty.

PMID- 1997346
TI  - Clinical care for myofascial pain.
AB  - Myofascial pain (MFP) is a regional muscle pain disorder characterized by
      localized tenderness in taut muscle bands and referred pain. Frequently, MFP is
      overlooked as a common cause of chronic pain because of the frequent association
      with joint dysfunction and other pain disorders and the multiple behavioral and
      psychosocial contributing factors that are often present. Nonetheless, studies
      have reported that MFP is present in a significant number of people. This article
      describes current concepts for the diagnosis and management of MFP.

PMID- 1997347
TI  - Long-term orthopedic appliance therapy.
AB  - This article illustrates the need for specific diagnosis of temporomandibular
      joint disorder patients. The latest concepts of different phases of treatment are
      reviewed and explained. A process of weaning and the necessity of proper
      appliance design to maintain tooth position and dental arch integrity are
      discussed.

PMID- 1997348
TI  - Chronic orofacial pain. A practical approach to differential diagnosis.
AB  - Successful diagnosis of chronic orofacial pain is a difficult task. This article
      attempted to simplify diagnosis by first classifying the orofacial pain on the
      basis of clinical characteristics into three basic pain categories: somatic,
      neurogenous, and psychogenic, and then according to the tissue system affected.
      An accurate and thorough history is essential, along with a detailed physical
      examination. In addition, an awareness of the local, systemic, and psychological
      causes of orofacial pain is necessary. The adage "what you don't know, you don't
      diagnose" is especially apt in regard to orofacial pain.

PMID- 1997349
TI  - Diagnostic anesthesia. Guidelines for the practitioner.
AB  - Diagnostic anesthesia is a special modality offering data that, when coupled with
      other diagnostic information, may help establish the diagnosis or a source of
      pain. Guidelines using injectable or general anesthesia have been reviewed. Most
      important is that diagnostic anesthesia only identifies a source of pain and not
      necessarily the source of the problem. This modality should complement and not
      replace a thorough medical history.

PMID- 1997350
TI  - Headache problems that can present as toothache.
AB  - Toothache of nonodontogenic origin may be better differentiated with the use of
      differential diagnostic blockade. Table 9 reviews the expected outcome of somatic
      block at the site of pain and when the nerve division or the site of nociception
      is blocked. Although there is considerable overlap, this technique together with
      a careful history and detailed physical examination will prevent many unnecessary
      irreversible treatments. If no sign of periapical pathology can be determined
      (radiography is normal) and the dental examination is nonrevealing, at least a 4
      month period should be allowed to elapse before considering any irreversible
      dental procedure. During this time pharmacologic trials may be attempted, bearing
      in mind the clinical presentation. Patients should be informed that it may take
      at least 4 months for the dental pathology to manifest and in the hope of
      preventing irreversible damage, careful observation accompanied by the
      pharmacologic trials will be carried out. The practicing clinician is encouraged
      to maintain a broad perspective of the differential diagnosis of toothache when
      the pathology is not obvious.

PMID- 1997351
TI  - Burning mouth syndrome.
AB  - In spite of the normal clinical appearance of the oral mucosa, BMS subjects do
      have demonstrated changes in sensory perception and salivary factors in addition
      to alterations in psychologic features. Although some of these changes may be
      suggestive of a peripheral or central dysfunction of small afferent nerve fibres,
      the extent of this alteration and its cause both remain unclear. The existence of
      changes other than psychologic, however, do weaken the proposition that BMS has a
      primarily psychogenic origin and suggests instead that future research should
      address the question of other organic changes in BMS.

PMID- 1997352
TI  - Acute and chronic postural abnormalities as related to craniofacial pain and
      temporomandibular disorders.
AB  - This article has focused primarily on the etiology of CFP and TMD that begins
      extrinsic to the stomatognathic system and may represent the causative factors
      behind continued patient complaints after medical and dental intervention. A
      close professional relationship between the dentist and physical therapist is
      essential. The knowledgeable physical therapist, through direct interaction with
      the patient's bodymind, can assist with facilitating change, restoring function,
      and increasing awareness. New ways of efficiently posturing and moving cannot be
      learned readily until old bodymind patterns are recognized. From here, the
      exciting mutual journey of discovery begins and the process continues to unfold
      for the therapist and client alike.

PMID- 1997353
TI  - Psychologic considerations in temporomandibular dysfunction. A biopsychosocial
      view of symptom formation.
AB  - Temporomandibular dysfunction often is conceptualized as having a significant
      psychologic component. After clarifying the implications that follow
      differentiation between acute and chronic pain, clinical features most commonly
      associated with the chronic or potentially chronic pain patient are presented. An
      attempt is made to present biopsychosocial or multifactorial models of symptom
      formation in a context that moves away from issues of specific etiology toward a
      dynamic interactional process involving predisposers, triggers, and buffering
      factors. The clinical presentation in temporomandibular dysfunction then reflects
      the final common pathway for a complicated matrix of biopsychosocial factors that
      varies from patient to patient.

PMID- 1997354
TI  - Special considerations in orofacial pain.
AB  - A pathologic dental condition is by far the most common cause of orofacial pain.
      There are, however, certain patients who possess and exhibit myriad signs and
      symptoms that mimic pathologic dental conditions but do not have a dental cause.
      These patients pose a diagnostic dilemma for the dental practitioner.
      Unfortunately, there are many documented cases of misdiagnosis and mismanagement
      in patients with deafferentiation pain, neuropathic pain, trigeminal neuralgia,
      and temporal arteritis. These orofacial pain disorders warrant special
      consideration for the dental practitioner and are reviewed in this article.

PMID- 1997355
TI  - Nocturnal bruxism and its clinical management.
AB  - Most individuals, both adults and children, engage in nocturnal bruxist activity
      at some point in their lives and to varying degrees. The tissues of the
      masticatory system will generally adapt to this behavior; however, in some
      individuals the capacity for adaption will be exceeded by the cumulative forces
      of this mandibular parafunctional behavior, resulting in pain and dysfunction of
      the masticatory system. This article discusses the history, nature, causes, and
      effects of bruxism as well as the diagnosis and therapy.

PMID- 1997356
TI  - Nonsurgical management of disc-interference disorders.
AB  - Disc-interference disorders are a group of intracapsular problems that make up
      one category of temporomandibular disorders. The dental profession's
      understanding of these disorders has changed greatly in recent years. This
      article reviews current concepts regarding the diagnosis and management of these
      disorders as revealed through recent clinical studies.

PMID- 1997357
TI  - Diagnostic imaging of the temporomandibular joint.
AB  - This article reviews the more commonly used imaging techniques for examining the
      temporomandibular joint. Emphasis is placed on assessment of their accuracy as
      diagnostic tests for pain, dysfunction, and intracapsular disease processes.

PMID- 1997358
TI  - Evaluation of temporomandibular joint sounds. Diagnostic analysis and clinical
      implications.
AB  - This literature review and survey highlights the controversies surrounding the
      significance of joint sounds in general, the problems and pitfalls of joint sound
      analysis and interpretation, and the degree of importance given peripheral and
      temporomandibular joint sounds by physicians and dentists. The instrumentation
      and devices currently proposed for use in the detection and interpretation of
      joint sounds may not meet the standards of validity, reliability, sensitivity,
      and specificity, and as pointed out by one investigator, "The only objectivity
      currently associated with these instruments is their ability to record sounds of
      undetermined origin." In addition, no solid evidence is available that these
      particular sounds, when detected, are both repeatable over time and distinctly
      characteristic for particular disorders or significant pathologic changes. Some
      degree of caution should be used, therefore, when interpreting joint sounds in
      the absence of significant signs and symptoms of temporomandibular disorders. The
      clinical significance of these same sounds may become more or less apparent
      relative to the information obtained in a comprehensive temporomandibular
      disorder evaluation and examination including both subjective and objective pain
      assessments, mandibular range of motion measurements, and the interpretation of
      radiologic findings.

PMID- 1997359
TI  - Temporomandibular joint surgery.
AB  - This article reviews the spectrum of temporomandibular joint surgery. Indications
      for surgical treatment are discussed. Techniques are presented in an orderly
      fashion, from simple to complex. Preoperative and postoperative care are
      reviewed.

PMID- 1997360
TI  - Federation of American Societies for Experimental Biology. 75th Annual Meeting.
      Atlanta, Georgia, April 21-25, 1991. Part I. Abstracts.

PMID- 1997361
TI  - Community treatment for the chronically mentally ill.

PMID- 1997362
TI  - Self-esteem: a concept of renewed clinical relevance.

PMID- 1997363
TI  - "Anyplace but the state hospital": examining assumptions about the benefits of
      admission diversion.
AB  - One function of contemporary psychiatric emergency services is to divert patient
      admissions from state hospitals. Underlying this mandate are a series of untested
      assumptions about the positive effects of admission diversion. The author
      examines these assumptions using data on inpatient admissions from a crisis
      intervention service. Although the service was successful in preventing first
      admissions to the state hospital, the rate of recidivist admissions increased.
      Inpatient treatment in general or private hospitals did not result in shorter
      lengths of stay or fewer bed days than state hospital treatment. Because patients
      could be sent to any of several hospitals, some located far from the catchment
      area, continuity of care and treatment in the local community were not advanced
      by diverting admissions from the state hospital.

PMID- 1997364
TI  - Group psychotherapy in acute treatment settings: theory and technique.
AB  - Group psychotherapy has long been a part of most inpatient and partial hospital
      programs, but conducting groups in these settings has become more difficult as
      the average patient stay has shortened. The authors integrate findings from
      previous research in which patients ranked the importance of several therapeutic
      processes in acute care groups, and they suggest a theory of group psychotherapy
      that incorporates realistic clinical objectives for these short-term settings.
      Seven therapeutic factors--self-responsibility, self-understanding, instillation
      of hope, group cohesiveness, catharsis, altruism, and universality--are
      identified as important in promoting patient change. Specific techniques to
      enhance these factors in short-term settings are recommended.

PMID- 1997365
TI  - The problem with interpreters: communicating with Spanish-speaking patients.
AB  - The information obtained from a non-English-speaking psychiatric patient through
      an untrained interpreter can be inaccurate and misleading. The authors briefly
      outline the most common errors that untrained interpreters make, including
      omission, addition, condensation, substitution, and role exchange. They present
      two case examples, one in which misinterpretation led to minimization of a
      patient's suicide attempt and the other in which a patient's suicidality was
      exaggerated. They conclude that clinicians should observe the behaviors of both
      the patient and the interpreter for indications of errors that might distort or
      obscure the communication.

PMID- 1997366
TI  - A biobehavioral model for hospital psychiatry in an era of increasing regulation
      and cost containment.
AB  - Psychiatric hospitalization is increasingly a target of cost reduction by
      employers and third-party payers. The authors describe an evaluation of a
      biobehavioral model for the treatment of a mixed population of public- and
      private-sector patients in the psychiatric unit of a general hospital under
      conditions of severe regulation and cost containment. The program combined
      behavioral-education technology based on principles of social reinforcement with
      the traditional medical model in which the psychiatrist specified the patient's
      individual treatment within the general programmatic framework. Patient progress
      was monitored using standardized clinic rating scales, which showed that between
      85 and 96 percent of the patients had improved significantly at discharge after
      an average stay of 12 days. Based on that and other findings, the authors believe
      that the new programmatic technology of biobehavioral psychiatry has the
      flexibility to ameliorate the adverse effects of increasing regulation and cost
      containment, even under demanding clinical conditions.

PMID- 1997367
TI  - Psychiatric visits to general hospital clinics by elderly persons and younger
      adults.
AB  - Findings of a study of mental health visits to general hospital outpatient
      clinics and emergency rooms by elderly persons and younger adults were compared
      with findings from an earlier survey of mental health visits to office-based
      physicians. In both studies, about half of the visits were to psychiatric clinics
      or to psychiatrists. However, the findings differed in that 43 percent of all
      visits to hospital clinics were for substance abuse, compared with only 4 percent
      of the visits to private physicians. Almost three-fourths of the hospital-based
      mental health visits by elderly patients were to psychiatric clinics, while only
      a third of the office visits by elderly patients were to psychiatrists. The
      authors discuss the policy implications of the high utilization of clinic
      services by elderly patients.

PMID- 1997368
TI  - Who is served by programs for the homeless? Admission to a domiciliary care
      program for homeless veterans.
AB  - Demographic and clinical data are presented on 4,138 veterans assessed in the 20
      site Department of Veterans Affairs (VA) Domiciliary Care for Homeless Veterans
      program during its first year of operation. More than two-thirds of the veterans
      who were screened had been hospitalized in VA medical centers during the year
      before assessment, and 34 percent were hospitalized at the time of assessment.
      Compared with veterans who were not admitted for residential treatment, veterans
      who were admitted were more likely to be previously involved in mental health
      treatment, literally homeless rather than at risk for homelessness, and without
      public financial support. Specialized service programs for the homeless such as
      the VA domiciliary care program may also be called on to play a broader role in
      the discharge and rehabilitative efforts of public mental health service systems.

PMID- 1997369
TI  - Previously unrecognized physical illnesses in psychiatric patients.
AB  - Studies of the prevalence of previously unrecognized physical illness among
      psychiatric patients have paid little attention to the treatment implications of
      such illness. The authors describe a study in California in which 78 inpatients
      received an augmented evaluation one to two weeks after their admission
      evaluation. The retest evaluation detected previously unrecognized physical
      conditions that were judged to be causal among patients and physical conditions
      that were judged to exacerbate the psychiatric condition among 56 patients. The
      authors discuss the treatment implications of the most common type of conditions
      detected, neurological and nutritional. They also delineate the barriers to
      recognizing and then treating previously unrecognized physical illnesses.

PMID- 1997370
TI  - Essential and nonessential roles for psychiatrists in community mental health
      centers.

PMID- 1997371
TI  - Melancholia and orders to restrict resuscitation.

PMID- 1997372
TI  - Anticholinergic psychosis in children: a case report.

PMID- 1997373
TI  - Prosecuting assaultive psychiatric inpatients.

PMID- 1997374
TI  - Family characteristics, substance abuse, and hospitalization patterns of patients
      with schizophrenia.

PMID- 1997375
TI  - Images of the homeless.

PMID- 1997376
TI  - Inspection anxiety and PTSD.

PMID- 1997377
TI  - Fragile sites and chromosome instability: the distribution of breaks induced by
      cis-diamine-dichloro-platinum (II) in Fanconi anemia lymphocyte cultures.
AB  - The distribution of chromosome breaks induced by the antitumor drug cis-diamine
      dichloroplatinum (II) in lymphocyte cultures from Fanconi anemia patients was
      analyzed. Breakpoints occurred nonrandomly over an arbitrarily defined human
      karyotype of 319 bands. These bands were classified according to either their
      banding pattern or their fragile site status (whether or not a fragile site of a
      given type is located at a chromosomal band). A significant involvement of G
      light and fragile site bands was detected. The preferential occurrence of breaks
      at fragile site bands was limited to common fragile site bands (essentially of
      the aphidicolin-type).

PMID- 1997378
TI  - Identification of a break-prone structure in the 9q1 heterochromatic region.
AB  - The unusual behaviour of the 9q1 human chromosome region is studied in various
      conditions. In controls with normal chromosomes 9, del(9q1) is the most frequent
      spontaneously occurring deletion. This deletion is highly inducible by melphalan,
      an S phase-dependent alkylating agent. This may correspond to the uncovering of
      pre-existing DNA breaks in this region. In a 46,XX,9qh+ control, melphalan does
      not induce deletions any more efficiently than in donors with normal chromosomes
      9. In a 46,XY,inv(9) (p11q1205) donor, all deletions of inv(9) affect the short,
      but not the long, arm. This indicates that the sensitive segment is not the whole
      heterochromatic region, but rather a limited structure. The high rate of
      rearrangements affecting this structure may be responsible for somatic crossing
      over, leading to loss of heterozygosity for 9q, and to the frequent occurrence of
      inv(9) in human populations.

PMID- 1997379
TI  - No evidence of linkage between the locus for autosomal dominant retinitis
      pigmentosa and D3S47 (C17) in three Australian families.
AB  - A linkage analysis has been performed on three Australian families segregating
      for autosomal dominant retinitis pigmentosa (ADRP). No evidence of linkage has
      been found in any of the pedigrees studied between the locus D3S47 and the gene
      for ADRP. The D3S47 locus was found to show very close linkage with the ADRP gene
      in a large Irish pedigree. Our study together with a similar report on a British
      family indicates that there is genetic heterogeneity in this disease.

PMID- 1997380
TI  - Assignment of the human CD9 gene to chromosome 12 (region P13) by use of human
      specific DNA probes.

PMID- 1997381
TI  - Molecular genetic analysis of factor X deficiency: gene deletion and germline
      mosaicism.
AB  - A case of homozygous factor X deficiency arising from the inheritance of two non
      identical gene deletions from heterozygous parents is described. One, a partial
      gene deletion, was localized to exons VII and VIII by a combination of Southern
      blotting and polymerase chain reaction (PCR) amplification of exon sequences. The
      other deletion, of maternal origin, probably involves the entire factor X gene.
      Restriction fragments associated with the exon VII + VIII deletion were present
      in three siblings including the homozygous proband. These fragments were however
      absent from the somatic cells of the father, a finding consistent with germline
      mosaicism.

PMID- 1997382
TI  - Synaptonemal complex analysis in a human male carrier of a 4;6 translocation:
      heterosynapsis without previous homosynapsis.
AB  - Silver-stained synaptonemal complexes in surface-spread pachytene nuclei from a
      man, heterozygous for a reciprocal translocation, were analysed by electron
      microscopy. Contrary to the classically expected cross-shaped configuration,
      extensive non-homologous pairings were observed with asymmetrical association in
      the lateral elements of the non-homologous arms of the quadrivalents. A possible
      role of the heterosynapsis in reproductive failure is discussed.

PMID- 1997383
TI  - Frequency and distribution of aneuploidy in human female gametes.
AB  - During the past 6 years, 14 cytogenetic studies on human oocytes recovered during
      in vitro fertilization procedures have been published; they report contradictory
      results. The present survey has pooled the more than 1500 oocyte chromosome
      complements examined to date, in order to determine generalized trends in
      chromosomal abnormalities of female gametes. The overall frequency of
      abnormalities in mature oocytes is 24.0% with a large majority of aneuploidies
      (22.8%) over structural aberrations (1.2%), which could be explained by the
      difficulty in the detection of structural abnormalities in oocyte chromosome
      sets. An analysis of the distribution of non-disjunction among all chromosomes
      was also performed. In the A, C, D, and especially in the G groups, there is a
      significant difference between the observed non-disjunction and the frequencies
      expected from an equal partitioning of non-disjunction among all chromosomes.
      These data are discussed with reference to the differences obtained from
      cytogenetic studies on human sperm and from investigations on spontaneous
      abortion.

PMID- 1997384
TI  - A pooling strategy for heterozygote screening of the delta F508 cystic fibrosis
      mutation.
AB  - A theoretical and practical approach to economize the analysis of large DNA
      sample numbers for identifying heterozygosity of the delta F508 mutation causing
      cystic fibrosis is presented. Sample pooling can reduce the number of polymerase
      chain reaction (PCR) tests for this mutation by up to 77%. Based on a
      mathematical model, the optimal number (n) of samples to be united in one pool is
      24 for a German population with a delta F508 heterozygosity incidence of about
      1/35. We show that the PCR method is sufficient to detect one heterozygote for
      the delta F508 mutation in a pool of up to 49 non-delated DNA samples.

PMID- 1997385
TI  - Consanguinity sans reproche.
AB  - In a family with two cystic fibrosis (CF) patients and consanguineous parents,
      DNA analysis showed that the CF in the children was not caused by homozygosity by
      descent, since two different mutations were involved. A formula is given for
      calculating the probability that parental consanguinity, if it exists, is
      causally related to the existence of an autosomal recessive disease in affected
      children.

PMID- 1997387
TI  - PAH 399 GTA (Val)----GTT(Val), a new silent mutation found in the Chinese.
AB  - A silent mutation or sequence polymorphism, an A to T substitution at codon 399
      in exon 11 of the phenylalanine hydroxylase (PAH) gene has been identified by DNA
      sequence analysis in the Chinese. The frequencies of this new mutation in normal
      and abnormal (phenylketonuria: PKU) genes are 0.005 and 0.09, respectively, based
      on the analyses of 100 apparently normal individuals and 39 PKU patients, as
      demonstrated by DNA amplification with polymerase chain reaction (PCR) and
      oligonucleotide hybridization methods. The results suggest that there is linkage
      disequilibrium between this polymorphism and PKU mutations in the PAH gene;
      approximately 10% of defect PAH alleles in the Chinese population may be
      identified with this sequence polymorphic marker.

PMID- 1997386
TI  - Autosomal dominant transmission of the NAME syndrome (nevi, atrial myxoma,
      mucinosis of the skin and endocrine overactivity).
AB  - A family affected in two generations with the NAME syndrome is described, and the
      literature on this phenotype reviewed. The term "NAME" was originally proposed as
      an acronym for "nevi, atrial myxoma, myxoid neurofibromata and ephelides".
      However, in order to give a more comprehensive description of this syndrome, we
      recommend the following alternative interpretation of "NAME": nevi, atrial
      myxoma, mucinosis of the skin, endocrine overactivity. Previous family
      observations suggested a dominant, and probably autosomal, inheritance but an X
      linked dominant transmission could not be excluded. We describe male-to-male
      transmission, strongly supporting the concept of the autosomal inheritance of
      this trait.

PMID- 1997388
TI  - Structural organization and polymorphism of the alpha satellite DNA sequences of
      chromosomes 13 and 21 as revealed by pulse field gel electrophoresis.
AB  - More than 30 unrelated individuals were analysed by pulse field gel
      electrophoresis for the alphoid centromeric sequences of chromosomes 13 and 21.
      These individuals had DNA patterns all different from each other and were most
      probably heterozygous at both loci. When several nuclear families were analysed
      in this manner, segregation was shown to be Mendelian, and no recombination event
      was detected over the 150 meioses scored in this study. Alphoid DNA sequences,
      therefore, constitute highly polymorphic centromeric markers, which can be used
      in linkage analysis for loci close to the centromeres of chromosomes 13 and 21.

PMID- 1997390
TI  - Allelic somatic mutations may explain vascular twin nevi.
AB  - Vascular twin nevi, i.e., telangiectatic nevus and nevus anemicus occurring
      together and adjacent to each other, can be explained as twin spots resulting
      from a somatic recombination. It is so far unclear, however, whether the
      postulated underlying autosomal recessive mutations are allelic. This problem can
      be approached by studying another cutaneous phenotype, phacomatosis
      pigmentovascularis. Within this diagnosis, several authors have reported the
      simultaneous occurrence of three different birthmarks, viz., a pigmentary nevus,
      a telangiectatic nevus and a nevus anemicus. These cases can also be explained as
      a twin-spot phenomenon, provided two of these nevi are considered allelic traits.
      The two vascular nevi are most probably allelic, whereas the pigmentary nevus may
      be a nonallelic component of this syndrome. In conclusion, phacomatosis
      pigmentovascularis provides circumstantial evidence suggesting allelism of
      somatic mutations giving rise to two different vascular nevi.

PMID- 1997389
TI  - No evidence for linkage of autosomal dominant proximal spinal muscular atrophies
      to chromosome 5q markers.
AB  - Two recent articles have reported the linkage of a gene for recessive spinal
      muscular atrophy (SMA) on the chromosome region 5q11.2-13.3. Our data show no
      linkage of the dominantly inherited forms of SMA to this chromosome region.

PMID- 1997391
TI  - Apolipoprotein A-IV protein polymorphism: frequency and effects on lipids,
      lipoproteins, and apolipoproteins among Mexican-Americans in Starr County, Texas.
AB  - Apolipoprotein A-IV phenotypes were determined by reprobing immunoblots initially
      typed for the apolipoprotein E polymorphism on a representative sample of Mexican
      Americans from South Texas. Typings on 331 individuals gave frequency estimates
      of 0.928, 0.066, 0.003, and 0.003 for alleles 1, 2, 3, and 4, respectively. To
      evaluate the effects of this polymorphic variability on lipid-related measures,
      mean levels between phenotypes were tested for equality following adjustment for
      age, sex, and body mass index. Analyses of levels of cholesterol, triglycerides,
      total high density lipoprotein, and its subfractions, low density lipoprotein,
      alpha and beta lipoproteins and apolipoproteins A-I, A-II, B, C-II, C-III, and E
      demonstrate that the A-IV genetic variability contributes minimally to normal
      variation of these quantitative factors in the population. Examination of the
      rare types, however, indicates the possibility of large metabolic effects whose
      follow-up may be useful for elucidating the metabolic roles of apolipoprotein A
      IV.

PMID- 1997392
TI  - Type III hyperlipoproteinemia in a patient with idiopathic hemochromatosis.
AB  - A 60-year-old man is reported with idiopathic hemochromatosis and type III
      hyperlipoproteinemia. Regular phlebotomy therapy and fenofibrate treatment
      favorably influenced the disorder of iron metabolism and the lipid disease.
      Evidence is given that both errors of metabolism are independently inherited
      diseases, although the symptoms of the first (idiopathic hemochromatosis) may
      aggravate the expression of the second (type III hyperlipoproteinemia).

PMID- 1997393
TI  - Frequency of the cystic fibrosis mutation delta F508 in Poland.

PMID- 1997394
TI  - IgE antibody production in rats against multiple components of excretory
      secretory products of the nematode Nippostrongylus brasiliensis.
AB  - Infection with the nematode Nippostrongylus brasiliensis (NB) induces the intense
      production of specific and non-specific immunoglobulin E (IgE) in rats. In the
      present study, we analysed NB-derived allergenic substances and the variability
      of IgE antibody production in response to these allergens in outbred Sprague
      Dawley rats. Two kinds of crude allergens were used: the excretory-secretory
      products (ES) of adult NB, and an extract of homogenized adult worms (AW). ELISA
      showed that IgE antibody titres to ES were more than five times higher than the
      titres to AW. In the homologous passive cutaneous anaphylaxis (PCA) reaction
      using serum from infected rats, as little as 50 micrograms of ES had a maximal
      PCA activity, while even 1 mg of AW still gave a slightly lower PCA titre. Thus,
      it appeared that ES contained more allergen than AW at the same amount of total
      proteins. By immunoblot analysis, at least six components were recognized by IgE
      antibodies from infected animals, and these components were exactly the same in
      both ES and AW. The results indicated that the allergenic components in ES and AW
      were the same molecules, and that only those molecules which could be excreted or
      secreted from living worms were allergenic. Among the array of allergens, 130,000
      and 70,000 molecular weight (mw) molecules were commonly recognized by IgE from
      all serum samples examined, while other components of the allergens were
      recognized variably by IgE antibodies from individual animals. These findings
      suggested that individual animals varied considerably in their IgE antibody
      production to the different constituents of the nematode allergens.

PMID- 1997395
TI  - Isolation of protective antigens from the gut of Boophilus microplus using
      monoclonal antibodies.
AB  - Monoclonal antibodies (mAb) were produced against midgut membrane (GM) antigens
      of Boophilus microplus. The isotypes of these mAb were established and their
      specificity characterized using double diffusion and Western blotting. GM
      antigens solubilized by Triton X-100 were precipitated by mAb QU13, and the
      precipitate was then injected into cattle to test for the presence of protective
      antigens. Vaccinated cattle challenged with 10-day-old larval ticks showed
      evidence of protection with a 62% reduction in eggs produced by ticks from
      vaccinated cattle compared to tick eggs from control cattle. In a second vaccine
      challenge experiment, the dose of precipitate was increased and greater than 99%
      protection was provided to these vaccinated cattle following challenge
      (calculated from tick egg weights compared to the control group). The solubilized
      antigen(s) precipitated by QU13 were subjected to SDS-PAGE separation and the
      calculated sizes of these molecules were greater than 200,000, 80,000, 74,000,
      62,000 57,000 and less than 30,000 MW.

PMID- 1997396
TI  - Oligodendrocyte-macrophage interactions in vitro triggered by specific
      antibodies.
AB  - The final pathway of myelin destruction in immune-mediated demyelination is
      phagocytosis by macrophages. As part of a systematic study of mechanisms of
      myelin-oligodendrocyte injury, we have used an in vitro approach to investigate
      interactions between rat oligodendrocytes and macrophages in order to identify
      the conditions under which macrophages adhere to and damage oligodendrocytes. No
      adherence was seen when macrophages alone were co-cultured with homologous
      oligodendrocytes. However, macrophage attachment to oligodendrocytes was
      triggered not only by antibody to the major cell-surface component
      galactocerebroside, but also by antibody to the quantitatively minor antigen,
      myelin-oligodendrocyte glycoprotein; immunocytochemical observations suggested
      that phagocytosis of myelin antigen also occurred. No such changes were seen in
      the presence of an irrelevant (anti-progesterone) antibody, or in the presence of
      activated complement. These results emphasize that a variety of antibodies,
      including those to minor myelin-oligodendrocyte antigens, may play a significant
      role in the development of demyelinated lesions.

PMID- 1997397
TI  - Effects of chlorpromazine on PMN-mediated activities in vivo and in vitro.
AB  - Polymorphonuclear neutrophils (PMN) play a central role in the acute inflammatory
      response and functions associated with phagocytosis and bacterial killing,
      including lysosomal enzyme release and superoxide anion (O2-) generation, are
      also implicated in tissue injury. We have studied the modulation by
      chlorpromazine (CPZ) on the effects of lipopolisaccharide (LPS) in vivo in mice.
      Pretreatment with CPZ (4 mg/kg) and, to lesser extent, promethazine, inhibited
      LPS-induced hypoferraemia and lethality in mice. We have also observed that CPZ
      (1-15 microns) inhibited lactoferrin release by PMN in vitro, suggesting that
      this effect could be responsible for the inhibition of hypoferraemia. We have
      also evaluated the effect of CPZ on other PMN functions implicated in tissue
      damage and inflammation, chemotaxis and O2- production. CPZ inhibited both
      activities, although it had chemokinetic activity per se. These data indicate
      that CPZ is a modular of PMN functions in vivo and in vitro and this effect could
      be directly implicated in the protective action of CPZ against endotoxic shock.

PMID- 1997398
TI  - Identification of an amino acid sequence in the laminin A chain mediating mast
      cell attachment and spreading.
AB  - PT18 mast cells and mouse bone marrow-derived mast cells have been shown to
      adhere and spread when in contact with a laminin substratum. Mouse bone marrow
      cells, however, first require activation with phorbol myristate acetate (PMA),
      ionophore, or antigen-specific IgE with antigen in order to exhibit these
      phenomena. Here, we have studied the interaction of these cells with three active
      synthetic peptides derived from different domains of laminin. PT18 cells and
      mouse bone marrow mast cells attached and spread on the 19 amino acid synthetic
      laminin A chain-derived peptide PA22-2, containing the active five amino acid
      sequence IKVAV, and this attachment did not require prior activation of the mouse
      bone marrow mast cells with PMA or IgE plus antigen. These cells did not adhere
      to the B1 chain peptide YIGSR-NH2 or the RGD-containing peptide from the A chain.
      PT18 cell adherence to laminin was inhibited by soluble peptide PA22-2, but not
      by either YIGSR-NH2, the RGD-containing, or control peptides. Antisera to the
      PA22-2 peptide completely abolished adherence to PA22-2, but only partially
      inhibited mast cell adherence to laminin. Antibody to the 67,000-32,000 MW
      laminin-binding protein receptor blocked cell adhesion to laminin and to the
      active A chain peptide. Thus, mast cell adhesion and spreading on laminin may be
      mediated by an interaction with the IKVAV sequence on the laminin A chain.

PMID- 1997399
TI  - Identification and characterization of host-protective T-cell epitopes of a major
      surface glycoprotein (gp63) from Leishmania major.
AB  - By using a series of overlapping synthetic peptides that cover more than 75% of
      the amino acid sequence of the major surface glycoprotein (gp63) from Leishmania
      major, 11 T-cell epitopes in CBA and BALB/c mice have been identified. Six of the
      peptides were recognized by T cells of CBA mice recovered from L. major
      infection, while one was recognized by the T cells from BALB/c mice recovered
      from the infection following sublethal doses of gamma-irradiation. Lymph node
      cells from mice immunized with the peptides also responded to a number of the
      same peptides (seven in CBA and one in BALB/c). Peptide p10-28 induced
      proliferative T-cell responses in both CBA and BALB/c mice. Five of the peptides
      (p10-28, p22-40, p289-309, p459-471 and p467-482) induced vigorous T-cell
      response in CBA mice but were not recognized by T cells from recovered mice. Four
      other peptides (p321-336, p364-476, p372-385 and p378-396) were recognized by T
      cells from recovered CBA mice but could not induce a T-cell response in normal
      CBA mice. Three peptides (p146-171, p289-309 and p395-414) were both able to
      induce a T-cell response and were recognized by T cells from recovered mice.
      However, only two peptides (p146-171 and p467-482) were able to activate T cells,
      which also recognized epitopes expressed by antigen-presenting cells infected
      with promastigotes. T cells induced by p146-171 and p467-171 or a mixture of
      these two peptides were mainly CD4+ and produced interleukin (IL-2) and
      interferon-gamma (IFN-gamma) but not IL-4 upon antigen stimulation in vitro.
      These two peptides also induced a classical delayed type hypersensitivity (DTH)
      response in CBA mice. Furthermore, CBA mice immunized with a mixture of the two
      peptides in Coryne parvum or entrapped in liposomes induced significant
      resistance against L. major infection. The implications of these results in terms
      of a synthetic vaccine against leishmaniasis and the mechanism of the induction
      of Th1 and Th2 cells are discussed.

PMID- 1997400
TI  - Murine memory B cells are multi-isotype expressors.
AB  - Flow cytometric analyses of the surface immunoglobulins of murine memory B cells
      revealed the existence of populations expressing multiple isotypes, including an
      IgM+/IgG+ population that could be stimulated in vitro with antigen to secrete
      both IgM and IgG. Female BALB/c mice were immunized with R-phycoerythrin (RPE), a
      fluorescent photosynthetic accessory protein from red algae. Pooled splenocytes
      from these mice at different stages of immunization were stained with RPE as well
      as with allophycocyanin- and fluorescein-conjugated anti-isotype antibodies and
      analysed on a two-laser FACS. RPE-binding cell sub-populations were defined and
      selectively sorted to verify their phenotype and to demonstrate that the various
      subpopulations (IgM+/IgG+, IgM+/IgG-, IgM-/IgG+) had different isotype-secretion
      patterns when challenged with RPE in vitro. These results re-affirm the notion
      that a transcriptional processing mechanism may be responsible for the
      simultaneous expression of multiple isotypes in memory cells.

PMID- 1997401
TI  - Regulation of interleukin-1 and tumour necrosis factor gene expression in
      myelomonocytic cell lines by 1,25-dihydroxyvitamin D3.
AB  - 1,25-dihydroxyvitamin D3[1,25-(OH)2D3] is capable of regulating cells in the
      immune system and affects cytokine production by both T lymphocytes and by
      monocytes. We examined the effects of 1,25-(OH)2D3 on the regulation of
      interleukin-1 beta (IL-1 beta) and tumour necrosis factor-alpha (TNF-alpha) genes
      in HL-60 and U937 cells. 1,25-(OH)2D3 alone only induced low level expression of
      the genes for these cytokines. Phorbol 12-myristate 13-acetate (PMA) strongly
      induced the transcription of these genes, whilst the addition of 1,25-(OH)2D3 to
      PMA-stimulated cells caused a further dose-dependent synergistic increase in the
      mRNA for both cytokines in U937 cells. In PMA-stimulated HL-60 cells, 1,25
      (OH)2D3 increased the mRNA for IL-1 beta but not that for TNA-alpha, These
      differences may be related to the different stage of myeloid differentiation in
      HL-60 and U937 cells.

PMID- 1997403
TI  - Presence of Ca2+ is obligatory for the cytotoxic activity of dengue virus-induced
      cytotoxic factor.
AB  - The present study was undertaken to investigate the role of calcium ions (Ca2+)
      in the cytotoxic activity of the cytotoxic factor (CF) produced by T lymphocytes
      of the dengue type 2 virus (DV)-infected mouse spleen. It was observed that CF
      prepared in Ca2(+)-free medium had no cytotoxic activity on normal mouse spleen
      cells suspended in Ca2(+)-free medium but had activity on cells suspended in
      medium having Ca2+. The cytotoxic activity of CF was restored by substitution
      with calcium chloride, the optimal dose being 10(-7) M. CF induced influx of Ca2+
      as measured by uptake of radiolabelled calcium chloride (45Ca), in the
      susceptible target cells, macrophages (M phi) and T lymphocytes, but had no
      effect on CF-resistant B lymphocytes. Calcium channel blocking drugs, like
      verapamil, nifedipine and diltiazem, inhibited the cytotoxic activity of CF and
      also the CF-induced influx of 45Ca in M phi and T cells. Thus, presence of Ca2+
      is obligatory for the cytotoxic activity of CF and the cell death is associated
      with increased intracellular Ca2+.

PMID- 1997402
TI  - Interleukin-8 induces neutrophil transendothelial migration.
AB  - Interleukin-8 (IL-8) is a potent neutrophil chemotactic stimulant. We have used
      chemically synthesized IL-8 to investigate its role in human neutrophil adhesion
      and transendothelial migration. IL-8 enhanced the adhesiveness of human
      neutrophils to plastic, and to both unstimulated and tumour necrosis factor (TNF)
      stimulated endothelial monolayers in vitro. Using a two-compartment model
      separated by a confluent endothelial monolayer, we have shown that IL-8
      chemotactic stimulation induced transmigration across the monolayer of up to 87.4
      +/- 2.1% of added neutrophils (compared to random unstimulated transmigration of
      2.2 +/- 0.7%), while chemokinetic stimulation led to transmigration of 21 +/-
      3.8% of neutrophils. Preincubation of endothelium with TNF also induced
      transmigration in this model, and was additive when combined with an IL-8
      chemotactic stimulus. Endothelial permeability was increased at maximal rates of
      chemotactic transmigration, which may correlate with increased permeability of
      vessels at inflammatory sites in vivo. The property of IL-8 to stimulate movement
      of neutrophils across endothelial monolayers in vitro supports the concept of a
      central role for this molecule in the accumulation of neutrophils at inflammatory
      lesions in vivo.

PMID- 1997405
TI  - Human markers for IgG2 and IgG4 appear to be on the same molecule in the
      chimpanzee.
AB  - It has been reported that all four immunoglobulin G (IgG) subclasses present in
      human serum are also present in chimpanzee serum, as detected with antibodies
      specific for the human IgG subclasses. We used monoclonal antibodies (mAb)
      specific for human IgG subclasses to measure concentrations of the four
      subclasses in the chimpanzee sera. Initial ELISA studies indicated that epitopes
      for all four human subclasses are present in chimpanzee sera. The concentrations
      of IgG1, IgG2 and IgG3 were similar in human and chimpanzee sera, but the
      registered concentrations of IgG4 were different. Absorption of IgG2-reactive
      material from chimpanzee serum with IgG2 mAb resulted in removal of IgG4-reactive
      material as well. Conversely, absorption of IgG4-reactive material removed IgG2
      reactive material. IgG2-reactive material, isolated from chimpanzee serum using
      solid-phase anti-IgG2 mAb, reacted with anti-IgG4 mAb, and isolated IgG4-reactive
      material reacted with anti-IgG2 mAb. Three anti-IgG2 mAb and five anti-IgG4 mAb,
      each of which react with separate epitopes on their respective human isotype,
      were used in these studies. We conclude that chimpanzee serum contains only three
      IgG isotypes related to those of humans, one of which contains determinants
      related to both human IgG2 and IgG4.

PMID- 1997404
TI  - IgA antibodies in the bile of rats. V. Primacy of the GALT as a source of IgA.
AB  - In each of a series of rats the common bile duct and the thoracic duct (cisterna
      chyli) were cannulated so that both bile and thoracic duct lymph could be
      collected quantitatively for several hours. The concentrations of IgA in samples
      of lymph and bile were measured by radioimmunoassay so that the output of IgA per
      unit time could be calculated. Although the output of IgA in the lymph did not
      decline significantly, the output in the bile fell so that by 2 hr it had been
      reduced to less than 20% of the peak value. Similar experiments in rats which had
      been immunized actively by injecting antigens into the GALT showed a
      corresponding rapid decline in titres of specific biliary antibodies after
      fistulation of the thoracic duct. The low levels of IgA in the bile of rats that
      had been drained of thoracic duct lymph were restored quickly to normal values by
      the intravenous infusion of a volume of thoracic duct lymph equal to that which
      had been lost; this restoration was transient, and the concentration of IgA in
      the bile soon declined again after the infusion ceased.

PMID- 1997406
TI  - Augmented production of granulocyte-macrophage colony-stimulating factor and
      alpha/beta interferon in mice inoculated with heat-killed Corynebacterium
      liquefaciens.
AB  - We demonstrated that heat-killed Corynebacterium liquefaciens bacteria, as a
      known potent host immune activity modulator, stimulate spleen cells to produce
      granulocyte-macrophage (GM) colony-stimulating factor (CSF) and another CSF with
      similar activity, as well as alpha/beta interferon, when injected intravenously
      into mice. Alpha/beta interferon was shown to be produced by C. liquefaciens
      activated plastic-G-10 column-adherent cells (A cells) in a thymus-independent
      manner. In contrast, augmented production of GM-CSF required the action of C.
      liquefaciens-activated T lymphocytes that collaborated with normal A cells. Non-T
      spleen cells from C. liquefaciens-stimulated athymic mice, however, produced an
      alternative CSF that partially replaced GM-CSF. Correspondingly, the numbers of
      GM-producing CFU developing in cultures of spleen cells from C. liquefaciens
      treated euthymic or athymic mice were 10 to 30 times higher than those in
      cultures of spleen cells from untreated mice. These results suggest that gram
      positive rods such as C. liquefaciens activate T and A cells for production of
      multiple cytokines and that potential cooperative actions of these cytokines
      underlie the known immunomodulatory action of coryneforms.

PMID- 1997407
TI  - Identification and characterization of proteinase K-resistant proteins in members
      of the class Mollicutes.
AB  - Proteins resistant to proteinase K are rare because of the potency, wide pH
      optimum, and low peptide bond specificity of this enzyme. Previously, only the
      prion proteins associated with transmissible spongiform encephalopathies,
      possibly related proteins in the mollicute Spiroplasma mirum, and proteinase K
      itself have been reported. We identified a new proteinase K-resistant protein,
      p40-pr, in two strains of Mycoplasma hyorhinis and in extracts of these
      organisms. p40-pr's are similar to prion proteins in their resistance to high
      doses of proteinase K and in the reversal of this resistance by strong denaturing
      conditions. However, p40-pr's were distinct immunologically, in relative
      molecular mass, and in their method of extraction. Two immunologically related
      forms of p40-pr were identified on sodium dodecyl sulfate (SDS) gels and Western
      immunoblots, a 40-kDa species in boiled samples and a 120-kDa species dissociable
      by boiling in SDS. Reduction with 2-mercaptoethanol did not affect the mass of
      p40-pr's or the 120-kDa forms. The development of proteinase K resistance of p40
      pr correlated to age-dependent increases in organism protein-lipid ratios. p40-pr
      like proteinase K-resistant proteins of 46 to 50 kDa were identified in four of
      eight additional species of the class Mollicutes but not in S. mirum. However,
      these mycoplasmal proteins did not react with antibody to the denatured 40-kDa
      form of M. hyorhinis p40-pr purified by electroelution. The chromatographically
      purified 46-kDa proteinase K-resistant protein of Mycoplasma orale was an
      arginine deiminase.

PMID- 1997408
TI  - Anti-Borrelia burgdorferi antibody response over the course of Lyme
      neuroborreliosis.
AB  - Characteristic findings on examination of cerebrospinal fluid (CSF) in Lyme
      neuroborreliosis include mononuclear pleocytosis, oligoclonal immunoglobulin G
      (IgG) bands, and evidence for local production of specific antibodies. We
      utilized an immunospot assay to detect cells secreting anti-Borrelia burgdorferi
      antibodies of different isotypes over the course of disease. Such cells were
      detected in CSF from 13 consecutive patients with neuroborreliosis examined
      before treatment. IgG antibody-secreting cells were present in high numbers
      (mean, 32 cells per 10(4) CSF cells), whereas IgA and IgM antibody-secreting
      cells were found less frequently and at lower numbers (mean, 5 and 6 cells per
      10(4) CSF cells, respectively). Clinical improvement after penicillin treatment
      was paralleled by a rapid decline of antibody-secreting cells in CSF, but they
      were still detected, although at lower numbers, in 5 of 10 patients examined more
      than 6 months after treatment. This specific B-cell response persisted despite
      clinical improvement. Whether it reflects persistence of antigen is unsettled.

PMID- 1997409
TI  - Influence of prevaccination immunity on the human B-lymphocyte response to a
      Haemophilus influenzae type b conjugate vaccine.
AB  - The purpose of this study was to investigate whether preexisting immunity to
      components of a polysaccharide-protein conjugate influences the B-lymphocyte
      response to vaccination with the conjugate. Thirty-two healthy adults were
      vaccinated once or twice with a conjugate (PRP-D) consisting of Haemophilus
      influenzae type b capsular polysaccharide (PRP) and diphtheria toxoid (DT), and
      the response was related to the prevaccination levels of PRP and DT antibodies.
      Positive correlations were found between increases in plasma PRP (median, 32.0
      micrograms/ml) and DT (1.14 IU/ml) antibodies and numbers of circulating PRP and
      DT antibody-secreting cells (AbSC) (postvaccination days 6 to 9). The B-cell
      responses (antibody response and AbSC) to both PRP and DT correlated positively
      with prevaccination levels of anti-DT. DT AbSC appeared earlier (peak, day 7)
      than PRP AbSC (peak, day 8). Individuals whose PRP AbSC peaked early (day 7) had
      higher prevaccination anti-DT levels than those who peaked later (P less than
      0.05). In contrast, the prevaccination levels of anti-PRP did not correlate
      significantly with the magnitude of the antibody or AbSC response and did not
      affect the kinetics of the AbSC. Following revaccination with PRP-D, small
      increases in the level of PRP antibodies (median, 2.9 micrograms/ml; n = 11) were
      found; no significant increase in the level of DT antibodies was seen. The
      numbers of PRP AbSC were lower (P = 0.04) and peaked earlier (day 7) than after
      the first vaccination. The isotype pattern of PRP AbSC, which was dominated by
      immunoglobulin A (IgA) after the first vaccination, now showed a more equal
      distribution between IgG and IgA AbSC. It is concluded that after immunization
      with PRP-D both the magnitude and the kinetics of the antipolysaccharide B-cell
      response are influenced by prevaccination immunity to the carrier molecule.

PMID- 1997410
TI  - Two copies of Shiga-like toxin II-related genes common in enterohemorrhagic
      Escherichia coli strains are responsible for the antigenic heterogeneity of the
      O157:H- strain E32511.
AB  - Thirty-two clinical isolates of Shiga-like toxin (SLT)-producing Escherichia coli
      associated with single cases or outbreaks of bloody diarrhea, hemorrhagic
      colitis, the hemolytic uremic syndrome, or edema disease of swine were examined
      for multiple copies of genes belonging to the slt-I or slt-II toxin families.
      Five of 19 strains that were known to produce SLT-II or to hybridize to slt-II
      specific probes by colony blot were found by Southern hybridization to contain
      two copies of toxin genes related to slt-II. The genes for two toxins closely
      related to slt-II were cloned from one of the isolates, Escherichia coli O157:H-
      strain E32511. One copy of the operon was found to be essentially identical to
      slt-II; it differed from slt-II by only one nucleotide base. This single
      nucleotide difference did not affect the predicted amino acid sequence. The
      predicted amino acid sequence of the A subunit of the second operon was identical
      to that of SLT-II, but the predicted amino acid sequence of the B subunit was
      identical to that of the B2F1 toxin VT2ha. We designated this second operon slt
      IIc. Neutralization assays using several monoclonal antibodies and polyclonal
      antiserum prepared against SLT-II showed that SLT-IIc was antigenically related
      to but distinct from SLT-II.

PMID- 1997411
TI  - Expression and deletion analysis of the Trypanosoma brucei rhodesiense cysteine
      protease in Escherichia coli.
AB  - Trypanosoma brucei, the cause of African sleeping sickness, differentiates in the
      mammalian bloodstream from a long, slender trypanosome into a short, stumpy
      trypanosome. This event is necessary for infection of the tsetse fly and
      maintenance of the life cycle. We have previously shown that the stumpy form
      contains 10- to 15-fold-greater cysteine protease activity than either the
      slender form or the insect midgut procyclic, and we have isolated a cDNA encoding
      the protease. In order to determine whether the cDNA encodes the developmentally
      regulated cysteine protease, we have purified the protease from trypanosomes and
      have made a polyclonal antiserum against it. The trypanosomal protease gene was
      then expressed in Escherichia coli with three different methionines within the
      pre- and propeptides acting as initiation sites. In each case, a protein was
      synthesized that was recognized by an antiserum specific for the developmentally
      regulated trypanosomal cysteine protease. The protein synthesized from the more
      upstream initiation site within the propeptide was proteolytically active. The
      recombinant protease and the trypanosomal enzyme were identical with respect to
      peptide substrates and protease inhibitors. The protein remained active when
      synthesized in a truncated form lacking the nine consecutive prolines and carboxy
      terminus extension, indicating that the terminal 108 amino acids are not
      necessary for proteolytic activity.

PMID- 1997412
TI  - Mutations at rfc or pmi attenuate Salmonella typhimurium virulence for mice.
AB  - Insertion mutations were constructed in cloned pmi and rfc genes of Salmonella
      typhimurium, and these mutations were recombined (singly) into the chromosome of
      mouse-virulent S. typhimurium C5, displacing the wild-type alleles. Phage
      sensitivity profiles, lipopolysaccharide analysis, and DNA blotting all confirmed
      that the replacement events had occurred. The mutations were complemented by
      plasmid-borne wild-type alleles, as judged by the restoration of wild-type phage
      plaquing profiles and lipopolysaccharide production (both mutants) and the
      restoration of pmi-encoded enzyme production (pmi mutant). The virulence,
      persistence, and immunizing capacities of the mutants fed to mice were compared
      with those of the wild-type strain and complemented mutants. Both mutants were
      much reduced in virulence, with the rfc mutant being avirulent even at 10(9)
      bacteria per mouse. This mutant was also avirulent at up to 10(6) bacteria per
      mouse when administered intraperitoneally. Both the rfc and pmi mutant strains
      persisted in the Peyer's patches of the gut after feeding and were capable of
      colonizing the deeper tissues of the mice from such initial infective foci. Both
      mutant strains were effective as live oral vaccines (10(7) bacteria or more)
      against oral S. typhimurium challenge (10(4) 50% lethal doses; 6 x 10(8)
      bacteria) in mice.

PMID- 1997414
TI  - Effects of Bordetella bronchiseptica dermonecrotic toxin on the structure and
      function of osteoblastic clone MC3T3-e1 cells.
AB  - The effects of Bordetella bronchiseptica dermonecrotic toxin on the structure and
      function of a clonal osteoblastic cell line, MC3T3-E1, were investigated. The
      toxin induced a morphological change in the cells from a spindle shape to a
      spherical form with many blebs. The toxin-treated cells were viable and grew to
      form confluent cell layers composed of irregularly shaped cells and multinuclear
      cells. The toxin inhibited elevation of alkaline phosphatase activity in the
      cells in a dose-dependent manner at concentrations from 10 pg to 10 ng/ml. The
      accumulation of type I collagen in the cells was also reduced by the toxin. Since
      high alkaline phosphatase activity and accumulation of collagen are closely
      linked to differentiation of the cells into osteoblasts, it is considered likely
      that B. bronchiseptica dermonecrotic toxin impairs the ability of the cells to
      differentiate.

PMID- 1997413
TI  - Humoral and cellular defense against intestinal murine infection with Yersinia
      enterocolitica.
AB  - The role of phagocytes and the complement system as potential host defense
      mechanisms against bacterial infection were studied in mice with two isogenic
      strains of Yersinia enterocolitica serotype O8 differing in pathogenicity because
      of differences in plasmid content. Complement depletion in mice by
      intraperitoneal injection of cobra venom factor did not affect the course of
      colonization of the intestinal tissue by each strain, indicating that in mice
      complement is not essential for the elimination of these bacteria. This
      conclusion is supported by the fact that fresh murine serum had no bactericidal
      effect in vitro either on the pathogenic or on the nonpathogenic strain. However,
      in the intestinal tissue as well as in the peritoneal cavity, only the
      pathogenic, plasmid-bearing Y. enterocolitica strain survived, while the
      nonpathogenic, plasmidless strain was rapidly eliminated. Since elimination from
      the peritoneal cavity is due to phagocytosis by polymorphonuclear leukocytes and
      macrophages, resistance to phagocytosis in vivo seems to be the decisive factor
      determining the virulence of pathogenic Y. enterocolitica strains.

PMID- 1997415
TI  - Subclass and molecular form of immunoglobulin A antibodies to Actinobacillus
      actinomycetemcomitans in juvenile periodontitis.
AB  - Patients with juvenile periodontitis frequently have elevated levels of serum
      immunoglobulin A (IgA) antibodies to antigens of Actinobacillus
      actinomycetemcomitans. IgA occurs in two subclasses, IgA1 and IgA2, and in
      monomeric and polymeric forms. Because IgA1 is susceptible to cleavage by IgA1
      proteases produced by microorganisms found at mucosal sites and in the gingival
      crevice, we wished to determine the IgA subclass distribution of antibodies to
      antigens of A. actinomycetemcomitans. The molecular form was examined because it
      may indicate the origin of the IgA and because the form differs in acute and
      chronic infections. There is also evidence that monomeric and polymeric IgA have
      different biological functions. Serum was taken from patients with juvenile
      periodontitis before and at intervals during and after initiation of therapy. IgA
      subclass distribution was determined against a sonic extracts of A.
      actinomycetemcomitans ATCC 2952a (serotype b) by using monoclonal anti-subclass
      reagents in an enzyme-linked immunosorbent assay. To determine the molecular form
      of the antibodies, sera were separated by high-performance liquid chromatography
      on a size-exclusion column. Fractions were assayed for antibody activity by the
      enzyme-linked immunosorbent assay, and described above. The results of the
      subclass analysis of the sera indicated that while both IgA1 and IgA2 antibodies
      to A. actinomycetemcomitans sonic extract are often found before, during, and
      after treatment, IgA1 antibodies dominated the response. There was a predominance
      of monomeric IgA1 antibodies to A. actinomycetemcomitans sonic extracts in most
      samples before, during, and after treatment. The monomeric form is consistent
      with what is seen in other chronic infections. The predominance of IgA1
      antibodies implies that any protective effects of the IgA response to A.
      actinomycetemcomitans could be compromised by microbial IgA1 proteases.

PMID- 1997417
TI  - Molecular cloning and analysis of recombinant major antigens of Ehrlichia
      risticii.
AB  - The genome of Ehrlichia risticii, the etiologic agent of Potomac horse fever, was
      cloned in the lambda gt11 expression vector. The efficiency of recombinant phage
      production with different restriction fragments of E. risticii DNA was generally
      between 20 and 95%. The antigen-positive frequency, detected by immunoscreening
      with E. risticii antibodies, was between 8 and 40 per 10(4) recombinants. Four
      (70, 55, 51, and 44 kDa) major antigens of E. risticii were identified from the
      recombinant phages by using recombinant antigen-selected monospecific antibodies.
      Characterization of three (70, 55, and 44 kDa) of these recombinant antigens
      indicated that the 70- and 44-kDa polypeptides were beta-galactosidase fusion
      products that were dependent on isopropylthiogalactoside induction for
      expression; they contained about 50 and 73%, respectively, of the native
      polypeptides. The 55-kDa antigen was a nonfusion protein expressed independently
      of isopropylthiogalactoside induction; it was a complete protein with a molecular
      weight identical to that of its native counterpart. The cloned E. risticii DNAs
      from of the recombinants expressing 70-, 55-, and 44-kDa proteins were 3.5, 3.9,
      and 4.8 kb, respectively, in size, and they were unique. The insert DNAs
      hybridized to multiple restriction fragments of the genomic DNA, the sum of the
      sizes of which was much greater than that of the corresponding insert. Mice
      immunized with the affinity-purified 55-kDa recombinant antigen produced a high
      titer of antibody in serum as measured by an enzyme-linked immunosorbent assay
      and gave a monospecific reaction by Western immunoblotting. Challenge infection
      of these immunized mice showed low protection from clinical infection.

PMID- 1997418
TI  - Virulence of ureaplasmal urease for mice.
AB  - Ureaplasmas killed mice within 5 min after intravenous injection. The 50% lethal
      dose of whole ureaplasmal organisms was 32 micrograms per mouse, a value also
      found for crystalline jackbean urease. The reaction was specific to urease, since
      protection was afforded by intraperitoneal injection of 200 micrograms of
      flurofamide, a potent urease inhibitor. The finding that a similar lethal effect
      was produced by injection of 200 mumol of NH4+ indicates that the toxicity of
      urease is mediated by ammonium ions or free ammonia.

PMID- 1997416
TI  - Changes in the surface of Leptospira interrogans serovar grippotyphosa during in
      vitro cultivation.
AB  - Surface components of virulent and attenuated Leptospira interrogans serovar
      grippotyphosa were compared by using Triton X-114 solubilization and phase
      partitioning, immunoprecipitation of intact organisms, and freeze-fracture
      electron microscopy. Removal of the leptospiral outer membrane by using 0.1%
      Triton X-114 was demonstrated by whole-mount electron microscopy and by
      essentially complete solubilization of a lipopolysaccharidelike substance (LLS)
      from the outer membrane. Triton X-114 (0.1%) did not solubilize subsurface
      proteins, such as endoflagellar filaments or penicillin-binding proteins, which
      are markers for the periplasmic space and inner membrane, respectively. Triton X
      114 solubilized material from both the virulent and attenuated strains, which
      partitioned into the hydrophobic, detergent phase, contained LLS and major
      proteins of 41 and 44 kDa, which were also immunoprecipitable from intact
      organisms. The virulent strain contained greater amounts of an LLS component with
      an apparent molecular mass of 30 kDa (R(f) = 0.57), whereas the attenuated strain
      contained larger amounts of an LLS component with an apparent molecular mass of
      20 kDa (R(f) = 0.74). Differences in protein components between virulent and
      attenuated organisms were also detected; whereas the 41- and 44-kDa proteins were
      immunoprecipitated in equal amounts from both the virulent and attenuated
      strains, a 33-kDa protein was immunoprecipitated in significantly greater amounts
      from the attenuated strain. Quantitation of outer membrane particle density by
      freeze-fracture electron microscopy showed that both strains had a low
      transmembrane outer membrane protein content compared with that of typical gram
      negative bacteria. The virulent and attenuated strains had 443 and 990 particles
      (P less than 0.000001) per micron, respectively, in the concave outer membrane
      fracture face. These findings suggest that in vitro cultivation of L. interrogans
      is accompanied by quantitative and qualitative changes in both LLS and outer
      membrane-associated proteins.

PMID- 1997419
TI  - Monoclonal antibody immunotherapy in nude mice persistently infected with
      Cryptosporidium parvum.
AB  - Three groups of congenitally athymic nude mice were persistently infected
      following oral administration of 2 x 10(7) Cryptosporidium parvum oocysts. Two
      groups were treated once daily for 10 days with either neutralizing monoclonal
      antibody (MAb) 17.41 or an isotype control MAb. The third group received no
      treatment. Intestinal-infection scores were significantly decreased in nude mice
      treated with MAb 17.41 compared with isotype control MAb-treated and nontreated
      control groups (P less than 0.005). Biliary and pancreatic cryptosporidial
      infection scores were similar for the MAb 17.41-treated and isotype control MAb
      treated groups (P greater than 0.05).

PMID- 1997420
TI  - Further analysis of the sequence of the S1 subunit of pertussis toxin.
AB  - The two published sequences of the pertussis toxin operon differ in 3 bp in the
      S1 subunit gene. In this report, we provide evidence that Bordetella pertussis
      strains are able to produce active pertussis toxin only when they contain one of
      the two possible nucleotide sequences.

PMID- 1997421
TI  - Blood stage-induced Plasmodium brasilianum infection in the squirrel monkey
      induces antibodies which react with the circumsporozoite protein.
AB  - A blood stage-induced P. brasilianum infection in a naive squirrel monkey induced
      antibodies which reacted with the circumsporozoite protein of the parasite.
      Titers increased with duration of infection and persisted for 3 months after
      cure. In an immunoblot, these antibodies detected two polypeptides with molecular
      weights identical to those of the circumsporozoite protein and its precursor.

PMID- 1997422
TI  - Plasmodium falciparum ring-infected erythrocyte surface antigen is released from
      merozoite dense granules after erythrocyte invasion.
AB  - Electron microscopy was used to study the fate of Plasmodium falciparum ring
      infected erythrocyte surface antigen after merozoite invasion by using
      postembedding immunolabeling. The antigen was localized to small dense granules
      located centrally or laterally in free merozoites. In newly invaded erythrocytes,
      labeling was found in pockets of the parasitophorous vacuole space or in
      aggregates closely associated with the parasitophorous vacuole. These patterns
      indicate that ring-infected erythrocyte surface antigen is contained in merozoite
      dense granules that are released after merozoite invasion and not via apical
      rhoptry ducts at the time of merozoite attachment.

PMID- 1997423
TI  - Sequence diversity of the 60-kilodalton protein and of a putative 15-kilodalton
      protein between the trachoma and lymphogranuloma venereum biovars of Chlamydia
      trachomatis.
AB  - DNA from Chlamydia trachomatis serovars L3, C, and E corresponding to the open
      reading frames of the 60-kDa protein and of a putative 15-kDa protein was
      sequenced. The open reading frames coding for the 60-kDa protein had 1,641 bp in
      the three serovars. Compared with the L3 serovar, there were 9 and 11 amino acid
      changes in the C and E serovars, respectively. The open reading frames
      corresponding to the putative 15-kDa protein had 450, 456, and 453 bp for the L3,
      C, and E serovars, respectively. When compared with the L3 serovar, the C and E
      serovars had 14 and 16 amino acid differences, respectively.

PMID- 1997424
TI  - Rapid elimination of a synthetic adjuvant peptide from the circulation after
      systemic administration and absence of detectable natural muramyl peptides in
      normal serum at current analytical limits.
AB  - Although it is clear that muramyl peptides are involved in sleep associated with
      bacterial infection, their role in normal physiological sleep is less certain. It
      has been speculated that "natural" muramyl peptides, derived from degraded gut
      flora, may pass into the bloodstream, where they play a role in normal sleep (M.
      Karnovsky, Fed. Proc. 45:2556-2560, 1986). Muramic acid serves as a chemical
      marker for muramyl peptides, since it is not synthesized by mammals. After
      injection of synthetic muramyl dipeptide in rabbits, muramic acid was readily
      detected (after release by acid hydrolysis) in the circulation; however, levels
      rapidly decreased. This was an important positive control in assessing
      circulating levels of natural muramyl peptides. Muramic acid was not found in
      normal serum (detection limit, approximately 500 pmol/ml), demonstrating the
      absence of appreciable amounts of circulating natural muramyl peptides. At this
      time we are unable to provide supportive evidence for Karnovsky's hypothesis.

PMID- 1997425
TI  - Specific immune response in the human respiratory tract following oral
      immunization with live typhoid vaccine.
AB  - Specific antibody responses in the lower respiratory tract of human subjects to
      orally administered Salmonella typhi Ty21a are reported. These responses,
      predominantly of the immunoglobulin G class, were determined to be a transudate
      from serum. These results were supported by the similarity in responses to
      parenteral administration of heat-killed typhoid vaccine. Specific immunoglobulin
      A antibody was a poor contributor to the respiratory antibody response to either
      vaccine.

PMID- 1997426
TI  - Cell and receptor requirements for streptococcal pyrogenic exotoxin T-cell
      mitogenicity.
AB  - Streptococcal pyrogenic exotoxins (SPEs) A, B, and C, like other members of the
      pyrogenic toxin family, are able to cause toxic shock-like syndromes. One of the
      major properties of these toxins is the ability to induce T-cell proliferation.
      Characterization of T cell mitogenicity associated with SPEs A, B, and C was
      undertaken. SPEs A, B, and C were mitogenic for C57BL10/SnJ and BALB/cWAT T
      cells, with activities differing in intensity depending on the mouse strain and
      toxin employed. SPE-induced, T-cell-proliferative activity was dependent on class
      II major histocompatibility complex molecules expressed on antigen-presenting
      cells. The abilities of SPEs A, B, and C to preferentially stimulate murine cells
      with certain T-cell receptor V beta s were investigated by fluorescence-activated
      cell sorter analysis. SPE A preferentially activated T cells expressing V beta 8
      but not V beta 3, 6, or 11, while SPEs B and C preferentially stimulated T cells
      which did not express any of the tested V beta s.

PMID- 1997427
TI  - DNA supercoiling and environmental regulation of gene expression in pathogenic
      bacteria.

PMID- 1997428
TI  - Effects of cytochalasin D and methylamine on intracellular growth of Legionella
      pneumophila in amoebae and human monocyte-like cells.
AB  - A cloned and axenically cultured strain of Hartmannella vermiformis was used as a
      model to study intracellular multiplication of Legionella pneumophila in amoebae.
      The growth of L. pneumophilia in both H. vermiformis and a human monocyte-like
      cell line (U937) was investigated with cytoskeletal and metabolic inhibitors. L.
      pneumophila replicated only intracellularly in these cellular models, and
      electron microscopy showed ultrastructural similarities in the initial phase of
      multiplication. Treatment of amoebae with an inhibitor of microfilament-dependent
      phagocytosis (cytochalasin D, 0.5 or 1.0 micrograms/ml) did not inhibit
      intracellular growth of L. pneumophila; however, intracellular multiplication was
      inhibited by treatment of U937 monocytes with the same concentrations of
      cytochalasin D. Methylamine (10 to 100 mM), an inhibitor of adsorptive
      pinocytosis, inhibited the replication of L. pneumophila in amoebae in a dose
      dependent manner. All doses of methylamine tested (10 to 50 mM) inhibited growth
      of L. pneumophila in U937 monocytes. Cytochalasin D and methylamine had no effect
      on the multiplication of L. pneumophila in culture medium or on the viability of
      amoebae or U937 monocytes. Intracellular replication of L. pneumophila in H.
      vermiformis may be accomplished by a cytochalasin D-independent mechanism, such
      as adsorptive pinocytosis. In contrast, both cytochalasin D- and methylamine
      sensitive mechanisms may be essential for the intracellular multiplication of L.
      pneumophila in U937 monocytes.

PMID- 1997429
TI  - Palmitoylated proteins in Ureaplasma urealyticum.
AB  - After incubation of Ureaplasma urealyticum serotype 8 in the presence of 3H
      labeled palmitic acid, about 25 acylated proteins were detected by
      electrophoresis and fluorography. Of these, at least six were shown to be
      antigenic by immunoprecipitation of solubilized palmitate-labeled cells with a
      homologous polyclonal serum. These six included the serotype 8-specific surface
      expressed 96-kDa antigen. After phase partition of palmitate-labeled cells with
      Triton X-114, all but six acylated proteins partitioned entirely into the
      detergent phase. The others, including the 96-kDa antigen, partitioned
      preferentially into the detergent phase and were apparently amphipathic. These
      results are consistent with the acylated proteins being mainly membrane
      associated.

PMID- 1997430
TI  - Helicobacter felis gastritis in gnotobiotic rats: an animal model of Helicobacter
      pylori gastritis.
AB  - The gastric spirillum Helicobacter felis, originally isolated from the cat
      stomach, colonizes the stomachs of germfree rats. Studies were designed to
      examine the pathological and serological responses of germfree rats inoculated
      orally with H. felis. At 2 weeks postinoculation, the gastric mucosa of germfree
      rats had lymphocytes and eosinophils scattered in small foci throughout the
      subglandular region of the antrum. Small numbers of lymphocytes were present in
      the subglandular portion of the antral mucosa that focally extended through the
      lamina propria towards the luminal surface. Eight weeks postinoculation, the
      inflammation was confined to the antrum. It was characterized by increased
      numbers of lymphocytes and eosinophils in the subglandular areas, with focal
      aggregates of lymphocytes in the submucosa. Some lymphoid aggregates extended
      from the submucosa through the muscularis mucosa and lamina propria to the
      luminal surface. H. felis was demonstrated with the Warthin-Starry stain,
      bacterial culture, and urease assay, particularly in the antrum. H. felis also
      produced a significant immunoglobulin G antibody titer at 2, 4, and 8 weeks
      postinoculation as well as a transitory immunoglobulin M response at 2 to 4 weeks
      postinoculation. Contact control rats were not infected, inferring that fecal
      oral spread of H. felis did not occur.

PMID- 1997431
TI  - Virulence plasmids of enteroinvasive Escherichia coli and Shigella flexneri
      integrate into a specific site on the host chromosome: integration greatly
      reduces expression of plasmid-carried virulence genes.
AB  - The ability of enteroinvasive Escherichia coli and Shigella flexneri to cause
      disease depends on the presence of a large virulence plasmid (pINV). In this
      report we show that pHN280, the pINV of the O135:K-:H- enteroivasive strain E.
      coli HN280, and pWR100, the pINV of S. flexneri serotype 5 strain M90T, are able
      to integrate into a specific site on the host chromosome. pINV-integrated HN280
      and M90T strains required methionine (Met-) to grow in minimal medium, were
      noninvasive, did not produce contact-mediated hemolysin, and had lost the ability
      to bind Congo red (Crb-) at 37 degrees C. Immunoblots of whole bacterial extracts
      from pHN280-integrated HN280 derivatives revealed that integration severely
      reduced the expression of ipa and virG (icsA) plasmid genes. Met- HN280 and M90T
      derivative strains spontaneously generated Met+ revertants that either contained
      excised forms of pINV or had lost pINV. Restriction analysis of excised pINVs
      showed that they either were virtually identical to parental pINVs (precise
      excision) or had suffered some deletion (imprecise excision). Precisely excised
      pINVs expressed the full pattern of virulence, whereas imprecisely excised pINVs
      were always Crb- and noninvasive. The revertion to Met+ was shown to be recA
      dependent, indicating that homologous plasmid and chromosomal DNA sequences are
      involved in the integration-excision process. The maintainance of pINV through
      integration and downregulation of its virulence genes may represent an
      advantageous mechanism for enteroinvasive bacteria, particularly when they are
      outside host cells and/or have to face adverse environmental conditions.

PMID- 1997432
TI  - Experimental infection of newborn pigs with an attaching and effacing Escherichia
      coli O45:K"E65" strain.
AB  - The ability of a nonenterotoxigenic, K88-negative porcine Escherichia coli strain
      of serogroup O45:K"E65" to induce attaching-effacing lesions was investigated in
      newborn pigs. Typical attaching-effacing lesions, characterized by intimate
      adherence of bacteria to mature enterocyte brush borders with effacement of the
      microvilli, were observed on light and electron microscopy. Bacteria were also
      seen in intracytoplasmic vacuoles of mature enterocytes and, in areas of heavier
      colonization, in the lamina propria of the intestinal mucosa. A moderate
      inflammatory response with mild focal ulceration of the intestinal mucosa was
      observed. In a sequential study, we observed that the attaching-effacing lesions
      were well established in the duodenum, jejunum, and ileum at 12 h postinoculation
      but did not develop in the cecum and colon until 24 to 48 h postinoculation,
      although bacteria had colonized the latter areas as early as 12 h
      postinoculation. Initially, bacteria were very intimately attached, with an
      irregular arrangement on the enterocyte apical cell membrane, and subsequently
      reoriented to form a typical palisade arrangement with a narrow regular gap
      between the bacterial cell wall and the enterocyte apical cell membrane. This
      phenomenon of early intimate attachment of irregularly disposed bacteria has not
      been reported for human enteropathogenic attaching and effacing E. coli and could
      represent a new and different mechanism of attachment and effacement to
      intestinal epithelial cells.

PMID- 1997433
TI  - Mapping the minimal contiguous gene segment that encodes functionally active
      Shiga-like toxin II.
AB  - Shiga-like toxin type II (SLT-II) is one of two antigenically distinct cytotoxins
      produced by enterohemorrhagic Escherichia coli that are believed to play a
      central role in the pathogenesis of enterohemorrhagic E. coli-induced disease.
      SLT-II is a bipartite toxin with an enzymatically active A subunit that inhibits
      protein synthesis and an oligomeric B subunit that binds to the glycolipid
      globotriaosylceramide on eukaryotic cells. In this study, functional boundaries
      of the slt-II operon were mapped. Mutant proteins lacking the last four amino
      acids from the carboxy terminus of the 70-amino-acid mature SLT-II B polypeptide
      had no cytotoxic activity. However, when only two amino acids were removed from
      the carboxy terminus of the B subunit, the cytotoxic activity of the holotoxin
      was not altered drastically. Furthermore, a 21-amino-acid extension to the
      carboxy terminus of the SLT-II B polypeptide was tolerated with a minimum
      reduction in cytotoxic activity of the holotoxin. Deletion of the region coding
      for amino acids 3 through 18 of the 296-amino-acid mature SLT-II A polypeptide
      resulted in complete ablation of the cytotoxic activity of the holotoxin as well
      as abolition of the enzymatic activity of the A subunit. Thus, it appears that
      both 5'- and 3'-terminal coding sequences are essential for function of the slt
      II operon.

PMID- 1997434
TI  - In vivo effects of anticytokine antibodies on isotype restriction in
      Mesocestoides corti-infected BALB/c mice.
AB  - Chronic infection of mice with the cestode Mesocestoides corti results in an
      antibody response restricted to immunoglobulins M (IgM) and G1 (IgG1). To
      determine which of the known lymphokines are involved in the restricted isotype
      response, we treated M. corti-infected mice with a panel of anticytokine
      monoclonal antibodies against interleukin-4 (IL-4), IL-5, IL-6, and gamma
      interferon. The effects of anti-IL-4 were of particular importance, since IL-4 is
      known to enhance IgG1 production and an IgG1 response predominates in infected
      animals. Interestingly, injection of anti-IL-4 alone had no effect on IgG1 levels
      at day 7 postinfection and actually enhanced levels at day 10. Decreases in IgM
      levels were observed in anti-IL-4-treated mice. Administration of anti-IL-5
      inhibited IgM production early in infection, but no effects on IgG1 levels were
      observed. Treatment of infected mice with anti-gamma interferon had no effect on
      any of the isotypes analyzed. Treatment of infected mice with anti-IL-6 antibody
      had the most dramatic effects, with inhibition of IgM and IgG1 by day 14 of
      infection. The transient expression of IgG3, which is sometimes observed very
      early in the infection process, was also inhibited by anti-IL-6, suggesting that
      the inhibition observed was not isotype specific. To determine whether cytokines
      were acting in concert to effect the high IgM and IgG1 levels in infected
      animals, anticytokine antibodies were also injected in combinations. However, the
      only combinations that inhibited IgG1 levels contained anti-IL-6, and the extent
      of inhibition was not greater than that of anti-IL-6 alone. Results are discussed
      in terms of the effects of cytokines on parasite-induced isotype expression and
      the potential for IL-4-independent mechanisms of IgG1 production.

PMID- 1997435
TI  - Analysis of adherence of Streptococcus defectivus and endocarditis-associated
      streptococci to extracellular matrix.
AB  - Pathogenesis of nutritionally variant streptococcal (NVS) endocarditis initiates
      with bacterial attachment to and colonization of the damaged heart valve surface.
      Underlying extracellular matrix (ECM) exposed to the environment during damage to
      cardiac endothelium provides additional receptors that could be involved in
      bacterial adherence. The ability of NVS and endocarditis-associated streptococci
      to bind ECM was investigated by using an enzyme-linked immunosorbent assay system
      that incorporated ECM secreted by baby hamster kidney and human umbilical vein
      endothelial cells in culture. Streptococcus defectivus, the major species
      isolated from NVS endocarditis cases, bound ECM of fibroblasts and endothelial
      cells, indicating that the ECM molecule involved in the binding was a common
      constituent of diverse matrices. The specific binding of S. defectivus to ECM was
      demonstrated by saturation binding and specific antibody inhibition studies. Of
      the 15 S. defectivus strains analyzed, 13 bound ECM, whereas Streptococcus
      adjacens and NVS serotype III strains were unable to bind the matrix. This
      selective binding suggested that S. defectivus binds to heart valves through a
      mechanism different from those of other NVS in subacute bacterial endocarditis. A
      survey of non-NVS streptococcal endocarditis isolates demonstrated that S.
      mutans, S. mitis, S. sanguis, and S. faecalis also bound ECM, whereas other
      viridans species were unable to bind the matrix.

PMID- 1997436
TI  - Macrophage colony-stimulating factor in murine candidiasis: serum and tissue
      levels during infection and protective effect of exogenous administration.
AB  - Serum and tissue concentrations of the macrophage-specific colony-stimulating
      factor (CSF-1) and the number of CSF-1-responsive cells in bone marrow were
      investigated in mice chronically infected with a low-virulence strain of the
      opportunistic zoopathogenic yeast Candida albicans. CSF-1 levels in serum, brain,
      kidney, liver, and lung were significantly increased shortly after infection and
      remained elevated during the 2 weeks preceding the onset of specific T cell
      dependent immunity. The number of monocytic precursor cells was also increased in
      the bone marrow of infected mice. When macrophages from naive donors were exposed
      in vitro to purified murine CSF-1, their anticandidal activity in vitro appeared
      to be enhanced. CSF-1 was also administered in vivo to prospective recipients of
      a lethal C. albicans challenge. The results showed that the factor could
      effectively potentiate the animals' resistance to the yeast, as shown by
      increased survival times and reduced recovery of viable C. albicans from the
      organs of the CSF-1-treated mice. Therefore, the present data suggest that CSF-1
      is likely to contribute to early resistance to fungal infection and could be
      successfully exploited in experimental models of antifungal immunotherapy.

PMID- 1997437
TI  - Clinical correlates of in vitro Plasmodium falciparum cytoadherence.
AB  - To determine whether isolates of Plasmodium falciparum have intrinsically
      different cytoadherent properties and whether these differences contribute to the
      clinical severity of human falciparum malaria, we studied the cytoadherence to
      C32 melanoma cells in vitro of 59 parasite isolates from patients with naturally
      acquired infections in Thailand. Parasitized erythrocytes adhere to these
      melanoma cells principally via the glycoprotein CD36, which is also expressed on
      most vascular endothelium. In vitro cytoadherence was significantly greater for
      isolates from patients with biochemical evidence of severe malaria. The
      cytoadherent properties of P. falciparum parasites may thus be a virulence factor
      in human falciparum malaria. However, there was no correlation between the degree
      of in vitro cytoadherence and cerebral symptoms, which suggests that other
      receptors and/or host factors may be important in the adherence of malaria
      parasites to cerebral vascular endothelium. The cytokines tumor necrosis factor,
      interleukin-1, and gamma interferon, which have been implicated in the
      pathogenesis of cerebral malaria and are known to promote intercellular adhesion
      in other systems, did not enhance the cytoadherence of P. falciparum isolates to
      C32 melanoma cells.

PMID- 1997438
TI  - Fluid replacement protection of rabbits challenged subcutaneous with toxic shock
      syndrome toxins.
AB  - Toxic shock syndrome toxin 1 (TSST-1) and streptococcal pyrogenic exotoxin A (SPE
      A) belong to a family of pyrogenic toxins produced by Staphylococcus aureus and
      Streptococcus pyogenes, respectively. Both toxins are responsible for causing
      toxic shock syndrome (TSS) and related illnesses, clinically characterized by
      multiorgan involvement. The most severe TSS symptom is acute hypotension and
      shock after the initial febrile response. In this study, we examined possible
      mechanisms of shock development in TSS, particularly the role of T-cell
      proliferation, endotoxin enhancement by toxins, and capillary leakage. American
      Dutch belted rabbits, with subcutaneously implanted miniosmotic pumps filled with
      either TSST-1 or SPE A, served as the animal model. For both TSST-1 and SPE A
      treated rabbits, administration of cyclosporin A prevented toxin-induced T-cell
      proliferation but failed to protect the rabbits. Polymyxin B treatment of
      rabbits, to neutralize endogenous endotoxin, partially protected rabbits from
      challenge with either exotoxin; two of six rabbits survived on day 2 when treated
      with only TSST-1, whereas six of six animals survived after challenge with TSST-1
      and polymyxin B. Similarly, with SPE A-treated rabbits, only 1 of 10 animals
      without polymyxin B treatment survived on day 8, but 4 of 6 rabbits survived on
      day 8 when given polymyxin B. Fluid replacement was successful in preventing
      lethality. Twelve of 14 rabbits survived when given TSST-1 with fluid, and all
      rabbits treated with SPE A and fluid survived. Finally, by using miniosmotic
      pumps, staphylococcal exfoliative toxin A and concanavalin A were administered to
      rabbits in an attempt to induce lethality. These two T-cell mitogens caused T
      cell proliferation but failed to induce lethality in rabbits. The data suggest
      that toxin interactions causing vascular leakage and to some extent endotoxin
      enhancement are of major importance in development of hypotension and shock in
      TSS. It appears that T-cell proliferation may not contribute significantly to the
      induction of shock and death.

PMID- 1997439
TI  - Effect of growth rate and pH on intracellular levels and activities of the
      components of the phosphoenolpyruvate: sugar phosphotransferase system in
      Streptococcus mutans Ingbritt.
AB  - The growth of Streptococcus mutants Ingbritt in continuous culture at low pH or
      high growth rates repressed the biosynthesis of the components of the
      phosphoenolpyruvate:sugar phosphotransferase system (PTS). The cellular
      concentrations of the soluble components HPr, enzyme I (EI), and EIII for mannose
      (IIIman) and EII activity for glucose, mannose, 2-deoxyglucose (2DG), and
      fructose were determined in membrane preparations from cells grown at pHs from
      8.0 to 5.0 and at dilution (D) or growth rates from 0.1 to 1.0 h-1. The cellular
      levels of HPr and EI varied less than threefold under all of the growth
      conditions tested. On the other hand, EII activity in membranes from cells grown
      at D = 0.1 h-1 was repressed by growth at pHs below 8.0, with cells grown at pH
      5.0 completely devoid of EII activity. In addition, cells grown at D = 0.5 and
      1.0 h-1 exhibited little PTS activity for glucose, mannose, and 2DG and twofold
      lower activity for fructose. These activities were stimulated by the addition of
      a membrane-free cytoplasmic fraction, and this activating activity was shown to
      be due to the presence of IIIman. Estimation of the cellular content of IIIman
      indicated that the synthesis of this factor was repressed by growth above and
      below pH 7.0 and was particularly sensitive to growth at high rates. These
      results indicate that with S. mutans Ingbritt, both pH and growth rate regulate
      the genes for the synthesis of EIIs involved in the phosphorylation of glucose,
      mannose, 2DG, and fructose and the gene for the formation of IIIman.

PMID- 1997440
TI  - Modifications of plasma fibronectin in cystic fibrosis patients.
AB  - Recurrent pulmonary infections with Staphylococcus aureus and Pseudomonas
      aeruginosa are a major problem in cystic fibrosis (CF), leading to severe and
      progressive deterioration of the respiratory tract. Fibronectin (FN) has a
      binding site(s) for S. aureus and Streptococcus pyogenes. This bacterial bindings
      site(s) was studied by using FN from patients with CF and comparing them with FN
      purified from the plasma of bronchitis and normal subjects by an enzyme-linked
      immunosorbent assay technique. We found a decreased binding of the CF FN to these
      bacteria in all seven CF patients. Other differences between the CF FN and normal
      FN were a marked modification in the pattern of peptide migration in
      polyacrylamide gel electrophoresis after hydrolysis with various proteinases and
      an increase or decrease of the total sugar content of the FN.

PMID- 1997441
TI  - Steady-state staphylococcal enterotoxin type C mRNA is affected by a product of
      the accessory gene regulator (agr) and by glucose.
AB  - The effects of the accessory gene regulator (agr) and glucose on staphylococcal
      enterotoxin type C (SEC) gene (sec+) expression were examined. For the agr
      studies, a Tn551 insertionally inactivated agr was transferred into two different
      sec+ Staphylococcus aureus strains. Western blot (immunoblot) analysis showed
      that each of the sec+ Agr- derivatives produced less extracellular SEC than their
      Agr+ parent strains. Analysis of Northern (RNA) blots was consistent with at
      least part of the agr effect being at the level of steady-state sec+ mRNA. We
      examined the glucose effect on sec+ expression by utilizing both a fermentor
      system with a completely defined amino acid-containing medium in which the pH of
      the medium was maintained at 6.5 and a shake flask system with a complex medium
      in which the pH was allowed to fluctuate during bacterial growth. In both
      systems, samples from the cultures containing glucose had less extracellular SEC
      and less steady-state sec+ mRNA compared with the control cultures which lacked
      glucose. An intact agr was not required for the glucose effect on sec+
      expression; MJB407, an Agr- sec+ strain, produced more SEC and had more steady
      state sec+ mRNA when grown in medium that lacked glucose compared with medium
      that contained glucose.

PMID- 1997442
TI  - Purification and characterization of a protective antigen from Eimeria tenella.
AB  - Chickens were partially protected against coccidiosis induced by Eimeria tenella
      by using extracts prepared from sonicated sporulated oocysts or from sonicated
      sporozoites. Following gel filtration of either extract, most of the protective
      antigens were confined to a single pool of proteins in the molecular mass range
      between 20 and 30 kDa. Further purification of proteins from the protective pool
      of sporulated oocyst extract yielded a protective polypeptide with a molecular
      mass of 26 kDa. An antiserum raised to this pool identified a polypeptide with a
      molecular mass of 22 kDa in the protective pool from a similarly prepared extract
      of sporozoites of E. tenella. In subsequent studies, this antiserum was used as
      an aid in cloning protective polypeptides.

PMID- 1997443
TI  - Characterization of bovine cellular and serum antibody responses during infection
      by Cryptosporidium parvum.
AB  - Cellular and serum antibody responses of calves were monitored for 23 days after
      oral inoculation of the calves with oocysts of Cryptosporidium parvum. In vitro
      blastogenic responses of peripheral blood lymphocytes were assessed after
      stimulation with a C. parvum preparation. Specific lymphocyte blastogenic
      responses to the parasite were detected 2 days after inoculation. Parasite
      specific antibody titers were demonstrable 7 days after inoculation with oocysts
      and achieved peak levels 9 days after inoculation, coinciding with oocyst
      shedding at 5 to 10 days after inoculation. Both lymphocyte and antibody
      responses remained elevated until the termination of the experiment.
      Immunoblotting the C. parvum preparation with serum from an infected calf
      revealed six major parasite antigens. Five of these antigens reacted on
      immunoblots from 7 to 14 days after inoculation with oocysts. A parasite antigen
      of approximately 11,000 molecular weight demonstrated intense reactivity on
      immunoblots from 7 to 23 days after inoculation. The 11,000-molecular-weight
      antigen also reacted on immunoblots with parenterally raised antioocyst and
      antisporozoite rabbit sera. These results indicate that cell-mediated as well as
      humoral immune responses are initiated by cryptosporidial infection in calves and
      that the 11,000-molecular-weight parasite antigen is immunodominant.

PMID- 1997445
TI  - Refractive surgery.

PMID- 1997444
TI  - Antibody-producing cells in peripheral blood and salivary glands after oral
      cholera vaccination of humans.
AB  - We examined whether immunization with a newly developed oral cholera vaccine
      would elicit gut-derived antibody-producing cells in the blood and in distant
      mucosal tissues, such as the minor salivary glands, in 30 adult Swedish
      volunteers. The results of this study demonstrated that this vaccine indeed
      induced production of specific antibody-producing cells against the cholera toxin
      B subunit in both peripheral blood and salivary glands. The response in blood,
      which after primary and booster immunizations comprised both immunoglobulin A
      (IgA) and IgG antibody-forming cells, was highly transient and preceded the
      response in salivary glands; the latter response was restricted to the IgA
      isotype. The results provide further evidence of the existence of a common
      mucosal immune system in humans. Furthermore, these findings support previous
      observations that in animals, the cholera toxin B subunit may be a useful carrier
      protein for preparing enteric vaccines against pathogens encountered at
      intestinal and extraintestinal mucosal sites.

PMID- 1997446
TI  - Topographical principles in keratorefractive surgery.

PMID- 1997447
TI  - Radial keratotomy: incision number, incision direction, peripheral redeepening,
      and multiple-depth incisions.

PMID- 1997448
TI  - Update on laser corneal surgery.

PMID- 1997449
TI  - Mechanical modulation of the corneal surface.

PMID- 1997450
TI  - Polysulfone intracorneal lenses.

PMID- 1997451
TI  - Radial thermokeratoplasty.

PMID- 1997452
TI  - The art of surgical correction for postkeratoplasty astigmatism.

PMID- 1997453
TI  - Hexagonal keratotomy: clinical experience with 483 eyes.

PMID- 1997454
TI  - Keratomileusis.

PMID- 1997455
TI  - Phakic anterior chamber intraocular lenses.

PMID- 1997456
TI  - Refractive keratoplasty with synthetic lens implants.

PMID- 1997457
TI  - The medical and legal ramifications of women with AIDS.

PMID- 1997458
TI  - Reduction of lumbar scoliosis by use of a heel lift to level the sacral base.
AB  - The relationship between unlevelness of the sacral base and scoliosis is unclear.
      A method for reducing mild lateral bend of the lumbar spine by use of a heel lift
      to level the sacral base was tested in adults. Special methods were used to
      demonstrate the weight-bearing plane of the sacral base and the angle of lateral
      bend radiographically. The procedure significantly decreased the unlevelness of
      the sacral base and significantly reduced the angle of lateral bend. The results
      suggest that an unlevel sacral base contributes to lumbar scoliosis and that use
      of a heel lift to level the sacral base in mild cases of lumbar scoliosis can be
      beneficial.

PMID- 1997459
TI  - Lose a piece of the rock: physician liability for failing to notify private third
      parties of HIV risk.
AB  - Since 1851, individuals have successfully sued physicians for injuries sustained
      through infectious disease transmission from the physicians' patients. Liability
      to third parties must be considered in the management of patients with infectious
      diseases. Because of this potential liability, physicians with human
      immunodeficiency virus-infected patients must consider notifying identified third
      parties of their respective risks of infection.

PMID- 1997460
TI  - Management of acute paroxysmal supraventricular tachycardia in pregnancy.
AB  - The treatment of paroxysmal supraventricular tachycardia (PSVT) in pregnancy is
      not unlike treatment for the general population. The physician should feel
      confident that the pharmacologic agents ordinarily used to treat this common
      problem in the general population are safe for both mother and fetus when
      administered under monitored conditions. In treating paroxysmal supraventricular
      tachycardia in pregnancy, when both vagal maneuvers and exhaustive medical
      therapy fail, synchronized, direct-current cardioversion is a safe and effective
      form of treatment.

PMID- 1997461
TI  - Pulmonary infiltrates associated with Vibrio vulnificus septicemia.
AB  - In the case described, fatal Vibrio vulnificus primary septicemia was complicated
      by development of diffuse pulmonary infiltrates. Clinical features of this
      recently discovered infectious disease are discussed. Various aspects of
      diagnoses of pulmonary infiltrates in patients with V vulnificus septicemia are
      also presented. Vibriosis should be suspected in patients with chronic,
      underlying, predisposing diseases, recent ingestion of raw seafood, and
      characteristic skin lesions.

PMID- 1997462
TI  - Basil Smith Cantrell, M.D.

PMID- 1997463
TI  - Mutagenic activity of some newly synthesized cytostatic 1-(2-chloroethyl)-4
      arylacyl-1-nitrososemicarbazides in the Salmonella/mammalian microsome assay.
AB  - Five experimental anti-leukemic agents, 1-(2-chloroethyl)-4-arylacyl-1
      nitrososemicarbazides, were synthesized and tested for genotoxicity in the
      Salmonella/mammalian microsome assay. No strong mutagenic activity could be
      detected when tested with the S. typhimurium TA98. A clear dose-dependent base
      pair-substitution mutagenic activity was observed with each compound when the
      tester strain TA100 was used with or without metabolic activation. The
      genotoxicity of the unsubstituted substance was similar to that of the known
      mutagenic cytostatic drugs, lomustin and carmustin, and was stronger than the
      mutagenicity of each substituted derivative.

PMID- 1997464
TI  - DNA methylation in the digestive tract of F344 rats during chronic exposure to N
      methyl-N-nitrosourea.
AB  - The formation of O6-methyldeoxyguanosine (O6-MedGuo) was determined by an immuno
      slot-blot assay in DNA of various tissues of F344 rats exposed to N-methyl-N
      nitrosourea (MNU) in the drinking water at 400 ppm for 2 weeks. Although the
      pyloric region of the glandular stomach is a target organ under these
      experimental conditions, the extent of DNA methylation was highest in the
      forestomach (185 mumol O6-MedGuo/mol guanine). Fundus (91 mumol/mol guanine) and
      pylorus (105 mumol/mol guanine) of the glandular stomach, oesophagus (124
      mumol/mol guanine) and duodenum (109 mumol/mol guanine) showed lower levels of O6
      MedGuo but differed little between each other. Thus, no correlation was observed
      between target organ specificity and the extent of DNA methylation. This is in
      contrast to the gastric carcinogen, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG),
      which preferentially alkylates DNA of the pylorus, the main site of induction of
      gastric carcinomas by this chemical. In contrast to MNU, the non-enzymic
      decomposition of MNNG is accelerated by thiol compounds (reduced glutathione, L
      cysteine), which are present at much higher concentrations in the glandular
      stomach than in the forestomach and oesophagus. During chronic exposure to MNNG
      (80 ppm), mucosal cells immunoreactive to O6-MedGuo are limited to the luminal
      surface [Kobori et al. (1988) Carcinogenesis 9:2271-2274]. Although MNU (400 ppm)
      produced similar levels of O6-MedGuo in the pylorus, no cells containing
      methylpurines were detectable by immunohistochemistry, suggesting a more uniform
      methylation of mucosal cells by MNU than by MNNG. After a single oral dose of MNU
      (90 mg/kg) cells containing methyl-purines were unequivocally identified using
      antibodies to O6-MedGuo and the imidazole-ring-opened product of 7
      methyldeoxyguanosine. In the gastric fundus, their distribution was similar to
      those methylated by exposure to MNNG, whereas the pyloric region contained
      immunoreactive cells also in the deeper mucosal layers. After a 2-week MNU
      treatment, the rate of cell proliferation, as determined by bromodeoxyuridine
      immunoreactivity, was only slightly enhanced in the oesophagus and in the fundus,
      but markedly in the forestomach and the pyloric region of the glandular stomach.
      It is concluded that the overall extent of DNA methylation, the distribution of
      alkylated cells within the mucosa and the proliferative response all contribute
      to the organ-specific carcinogenicity of MNU.

PMID- 1997465
TI  - Radiation-induced changes in lung tissue and development of fibrosis determined
      by quantitative morphometric methods.
AB  - This study presents results of morphometric investigations of mouse lungs after
      single irradiation. An automatic image analyser was used to monitor pathological
      changes in morphological structure, especially the size and distribution of
      collagen fibres, the thickness of the septa and the diameters of alveoli in the
      lung. Radiation-induced changes in the area of alveoli and septa as well as
      collagen content were seen 11 weeks after irradiation. A dose-dependent increase
      in tissue and decrease in alveolar surface as well as a quantifiable increase in
      radiation oedema were seen. The septa were thickened and the total collagen
      content increased in a dose-dependent manner. The morphometric methods used here
      are suitable for determining changes in lung structure, particularly those in
      collagen content in the early phase of a pathological response after thorax or
      total body irradiation for conditioning in bone marrow transplantation.

PMID- 1997466
TI  - Effect of zindoxifene on experimental prostatic tumours of the rat.
AB  - The anti-oestrogen zindoxifene was originally developed as a drug for the
      treatment of hormone-dependent mammary carcinomas. Experiments with rats bearing
      androgen-dependent prostatic tumours revealed anti-neoplastic activity of
      zindoxifene on these tumours also. Therefore, the inhibitory effect of this drug
      was studied in various prostatic tumour models in comparison to the anti
      oestrogen tamoxifen and to castration. The growth of the hormone-dependent
      Dunning R3327 H tumour was strongly inhibited by zindoxifene (4 mg/kg), which was
      more effective than tamoxifen (43% T/C vs 87% T/C, the ratios of tumour weights
      in control and drug-treated rats). Zindoxifene was able to delay the relapse of
      these tumours by 7 weeks in comparison to castration. The experiments with Noble
      Nb-R prostatic tumours showed that administration of zindoxifene (5 mg) is
      superior to castration (5% T/C vs 52% T/C). The growth of tumours in castrated
      rats was completely inhibited by administration of zindoxifene. Therefore a
      peripheral mode of action has to be assumed.

PMID- 1997467
TI  - Influence of gastrin, gastrin receptor blockers, epidermal growth factor, and
      difluoromethylornithine on the growth and the activity of ornithine decarboxylase
      of colonic carcinoma cells.
AB  - Polyamines are essential factors of cell growth and differentiation. Modulation
      of the cellular polyamine content by 2-difluoromethylornithine (DFMO) inhibiting
      ornithine decarboxylase (ODC), or by hormones inducing ODC, influences cell
      growth. Gastrin acts trophically on some colonic carcinomas and their growth is
      inhibited by gastrin receptor blockers. The mechanism of the trophic action of
      gastrin on colonic carcinomas is not known. In this study the effect of gastrin,
      gastrin receptor blockers, epidermal growth factor (EGF) and DFMO on growth and
      ODC activity of four human colon carcinoma cell lines (SW 403, SW 1116, LS 174 T
      and Lovo) was investigated. Growth and ODC activity of all cell lines were
      inhibited by DFMO. Growth of the SW 403 cell line was increased by gastrin and
      inhibited by the gastrin receptor blocker benzotrypte. The other cell lines did
      not respond to gastrin and the gastrin receptor blocker. In SW 403 cells ODC
      activity was increased by gastrin, and was also elevated after treatment with the
      gastrin receptor blocker. These in vitro results were confirmed by studies on
      tumours that developed from SW 403 cells in nude mice. Combination of benzotrypte
      and DFMO did not enhance the antiproliferative effect. EGF increased growth of SW
      403 cells, but no induction of ODC activity was measured. LS 174 T cells were not
      stimulated by EGF. Medium replacement was the strongest stimulus of ODC activity
      in SW 403 cells already inducing ODC after 3 h. During cell culture ODC activity
      was high after seeding and decreased continuously with increasing cell density.
      These data suggest that gastrin induces ODC in gastrin-sensitive colonic
      carcinoma cells. DFMO appears to be a valuable antiproliferative agent in colonic
      carcinoma cells.

PMID- 1997468
TI  - Second nonocular tumors in cured unilateral retinoblastoma patients.
AB  - According to recent data the incidence of second tumors in cured hereditary
      unilateral retinoblastoma patients is 20% within 10 years, 50% after 20 years and
      rises to 90% after 30 years. Nonhereditary unilateral retinoblastoma patients
      have not been regarded as susceptible for second nonocular tumors so far. A case
      is reported of such a patient having developed a second presacral retroperitoneal
      tumor after successful treatment of a nonhereditary unilateral retinoblastoma
      group V without intracranial extension or pulmonary metastases. Consequently all
      (hereditary and non-hereditary) retinoblastoma patients should receive at least
      quarterly intensive follow-up examinations after primary ophthalmologic
      treatment.

PMID- 1997469
TI  - Histogenesis of clear cell chondrosarcoma. An immunohistochemical study with
      osteonectin, a non-collagenous structure protein.
AB  - The histogenesis of clear cell chondrosarcoma is still unclear: Apart from
      typical clear cell tumor areas, extensive production of woven bone formation
      suggests within the clear cell cartilagenous stroma is an intriguing phenomenon.
      Three cases of clear cell chondrosarcoma documented in the Bone Tumor Registry of
      Westphalia were examined for their patterns of osteonectin expression, and
      compared with other bone tumors of either osseous or cartilaginous origin, and
      with normal cartilage tissue. Found predominantly in osseous structures, the
      protein osteonectin takes part in the formation of new bone. The three clear cell
      chondrosarcomas showed a strong immunoexpression of osteonectin in clear cell,
      chondroid and in osseous tumor areas. Similarly, evidence of osteonectin was also
      found in osteoblastic and in chondroblastic osteosarcomas as well as in
      osteoblastomas. In contrast, osteonectin could not be demonstrated in the
      chondrosarcomas and mesenchymal chondrosarcomas from our registry that were
      analysed for comparison, and was found only minimally in the fibroblastic areas
      of dedifferentiated chondrosarcomas. The chondroblastic tumor components were
      always negative. There was no immunoexpression of osteonectin either in fetal or
      adult intervertebral disc tissue. The present immunohistochemical study of
      osteonectin has distinctly separated clear cell chondrosarcoma from the other
      variants of chondrosarcoma, and aptly verified the specificity of this entity.
      Moreover, the study would call for further histogenetic evaluation of clear cell
      chondrosarcoma, since the pattern of osteonectin expression in that tumor seems
      to indicate an osteogenic rather than a chondrogenic origin.

PMID- 1997470
TI  - Carcinogenicity studies of masheri: pyrolysed tobacco product, in vitamin-A
      deficient Sprague Dawley rats.
AB  - The carcinogenicity of long-term feeding of masheri extract to animals in a
      vitamin-A-sufficient (SLO+) and deficient (SLO-) state was studied in Sprague
      Dawley rats by feeding daily dose of 3 mg extract over a period of 21 months. The
      phase I activating enzymes, the glutathione (GSH)/glutathione S-transferase (GST)
      detoxification system, and the hepatic and circulating levels of vitamins A and C
      were also monitored at 12 and 21 months. It was observed that the phase I enzyme
      activities were significantly higher in SLO+ than in SLO- rats at both 12 months
      and 21 months. Moreover, the SLO- masheri-treated animals also showed a decreased
      in the GSH/GST detoxification system while the reverse was observed in SLO+
      group. Masheri extract treatment significantly lowered the hepatic and
      circulating levels of vitamin A while a concurrent increase was observed in the
      vitamin C level. The extract was found to be tumorigenic in both the SLO+ and SLO
      groups. Benign tumours were observed in the SLO+ group while a high incidence of
      malignant tumours of the lung were observed in the SLO- group upon treatment with
      masheri extract.

PMID- 1997471
TI  - Porokeratosis and malignant skin tumors.

PMID- 1997472
TI  - Human exposure to genotoxic carcinogens: methods and their limitations.

PMID- 1997473
TI  - Combination chemotherapy with oral idarubicin and cyclophosphamide for metastatic
      breast cancer.
AB  - A group of 40 women with objectively measurable metastatic breast cancer was
      treated with idarubicin, 35 mg/m2 on day 1, and cyclophosphamide, 200 mg/m2 on
      days 2-5, both drugs being administered orally every 3 weeks. Of 37 evaluable
      patients, 4 (10.8%) achieved a complete response and 14 (37.8%) a partial
      response, for an overall response rate of 48.6% (95% confidence interval, 37.45%
      59.75%). In previously untreated patients the response rate was 58.3%, whereas it
      was 44% in patients previously exposed to cytotoxic drugs. The median duration of
      response was 6.5 months, and the median survival of all patients was 10.5 months.
      Moderate nausea and vomiting were common. Diarrhoea, which occurred in 37% of the
      patients, was usually short-lived. Alopecia was generally mild, myelosuppression
      was the dose-limiting toxicity. Grade 3-4 leukopenia occurred only in pretreated
      patients. In previously untreated patients it was generally of grade 1-2.
      Laboratory evidence of cardiotoxicity (greater than or equal to 20% decrease in
      the left-ventricular ejection fraction from the baseline value) was observed in 3
      out of 26 patients, who had at least two determinations of the left-ventricular
      ejection fraction, and was transient in nature. No cases of congestive heart
      failure were observed. These results indicate that the combination of idarubicin
      + cyclophosphamide represents a practical and effective regimen to be used in
      selected patients with advanced breast cancer.

PMID- 1997474
TI  - Fibroblasts derived from patients with dysplastic nevus syndrome are not more
      sensitive towards 254-nm and 312-nm ultraviolet light than fibroblasts from
      normal donors.
AB  - DNA repair capacity of 18 fibroblast strains from patients with dysplastic nevus
      syndrome, 5 of them with malignant melanoma, was investigated and their colony
      forming ability (D0) after UV exposure was determined as a measurement of this.
      Seventeen fibroblast strains from normal donors served as controls. The
      dose/response experiments included up to 11 dose levels and two UV wavelength
      ranges: UV-C (using a low-pressure mercury lamp emitting predominantly 254-nm
      light) and UV-B (artificial "sunlamp" radiation centering around 312-nm light).
      The exponential segments of the dose/response curves were analysed by linear
      regression and the negative reciprocals of the regression coefficients, D0, were
      calculated for each cell strain and each wavelength range. When comparing D0
      values of individual cell strains from patients with and without melanomas with
      the mean value for all normal donors, only 4 out of 18 showed increased
      sensitivity towards UV-B. This difference, however, was not statistically
      significant. On the contrary, weighted-mean D0 values for fibroblast strains from
      patients with and without melanoma were found to be slightly but significantly
      higher than those for normal donors (significance level: 5%), indicating that
      cell strains from these patients were less sensitive to UV light (UV-C and UV-B)
      of both wavelength. This result, which on the basis of current literature data is
      somewhat unexpected, holds true within the limits of experimental accuracy of +/-
      12%.

PMID- 1997475
TI  - Nuclear grading of renal cell carcinomas--is morphometry necessary?
AB  - Comparative investigations of subjective with objective nuclear grading methods
      of renal cell carcinomas are almost completely lacking. Therefore, we graded 94
      cases of this carcinomas by a simple, subjective microscopical estimation as well
      as by a morphogenetic measurement of nuclear area. Both procedures proved
      prognostically useful, but the best results were achieved by morphometry. By this
      method three prognostic groups of renal cell carcinoma were found, provided that
      the borderlines were drawn at 28 microns 2 and 60 microns 2, respectively.
      Particularly favourable and unfavourable cases could be separated from average
      ones, if the means and standard deviations of both the nuclear areas and the
      diameters were evaluated. Overall, morphometric nuclear analyses are highly
      desirable, if, for example, morphological data are to be used in the context of
      prognostic or therapeutic studies on renal cell carcinoma. However, there is a
      broad distribution of the values for individual cases so that, tumour
      biologically, no exact demarcation of prognostically different groups can be
      expected.

PMID- 1997477
TI  - Proceedings of the PET Data Analysis Workshop. New York, New York, 1-2 May 1989.

PMID- 1997476
TI  - 5-Hydroxytryptamine (serotonin) subtype 3 antagonists, a major step in
      prophylaxis and control of cytostatic and radiation-induced emesis.

PMID- 1997478
TI  - The spectral signature method for the analysis of PET brain images.
AB  - We introduce the concept of the metabolic centroid spectrum as the feature space
      to characterize the distribution of metabolic activity in three-dimensional
      brains. The method computes the metabolic centroid of a brain subvolume for each
      increment of metabolic activity occurring in the whole brain. The result is the
      metabolic spectral signature, a continuous three-dimensional curve whose shape
      reflects the distribution of metabolic rates in the brain. The method's
      sensitivity to metabolic distribution asymmetries is greatly increased over that
      of the metabolic centroid method, while retaining its advantages; it is almost
      invariant to head size, head positioning, photon scatter, and the positron
      emission tomography (PET) camera's full width at half-maximum. It does not
      require magnetic resonance, computed tomography, or x-ray images. To test the
      method we analyzed the metabolic PET images of 40 normal subjects and 20
      schizophrenics. The results show a unification of several metabolic
      characteristics of schizophrenic brains, such as laterality, hypofrontality,
      cortical/subcortical abnormalities, and overall brain hypometabolism, which were
      identified by different laboratories in separate studies using differing
      methodologies. Here they are presented by a single automatic objective method.

PMID- 1997479
TI  - Functional interactions in the brain: use of correlations between regional
      metabolic rates.
AB  - Correlation coefficients between pairs of regional metabolic rates have been used
      to study patterns of functional associations among brain regions in humans and
      animals. An overview is provided concerning the additional information about
      brain functioning this type of analysis yields. A computer simulation model is
      presented for the purpose of giving a partial validation for correlational
      analysis. The model generates a set of simulated metabolic data upon which
      correlational analysis is performed. Because the underlying pattern of functional
      couplings in the model is known, these simulations demonstrate that the
      correlation coefficient between normalized metabolic rates is proportional to the
      strength of the functional coupling constant and that correlational analysis
      yields information on regional involvement in neural systems not evident in the
      pattern of absolute metabolic values.

PMID- 1997480
TI  - A regional covariance approach to the analysis of functional patterns in positron
      emission tomographic data.
AB  - This article provides a complete description of the subprofile scaling model
      (SSM) approach to the analysis of positron emission tomography (PET) data. The
      goals and assumptions underlying the development of SSM are outlined, and its
      strengths and weaknesses are discussed. It is demonstrated that all obtainable
      information about regional ratios can, in theory, be derived from the SSM
      regional covariance patterns. A general constraint on the ability to effectively
      remove global variation while identifying region-specific information about PET
      data sets is outlined and discussed within the SSM framework. Finally, an
      extension of the SSM technique to the generation of disease-specific covariance
      patterns is demonstrated for paraneoplastic cerebellar degeneration, the acquired
      immune deficiency syndrome dementia complex, and Parkinson's disease, and the
      importance of multidimensional descriptions of disease, such as may be obtained
      from PET data using SSM, is emphasized.

PMID- 1997481
TI  - Statistical analysis of functional neuroimaging data: exploratory versus
      inferential methods.
AB  - In the following, various image processing and analytical techniques, whose
      efficiency has been demonstrated empirically by comparison with expert readings
      of hundreds of positron emission tomography (PET) studies, will be outlined
      briefly.

PMID- 1997482
TI  - Assessment of accuracy of PET utilizing a 3-D phantom to simulate the activity
      distribution of [18F]fluorodeoxyglucose uptake in the human brain.
AB  - A three-dimensional brain phantom has been developed to simulate the activity
      distributions found in human brain studies currently employed in positron
      emission tomography (PET). The phantom has a single contiguous chamber and
      utilizes thin layers of lucite to provide apparent relative concentrations of 5,
      1, and 0 for gray matter, white matter, and CSF structures, respectively. The
      phantom and an ideal image set were created from the same set of data. Thus, the
      user has a basis for comparing measured images with an ideal set that allows a
      quantitative evaluation of errors in PET studies with an activity distribution
      similar to that found in patients. The phantom was employed in a study of the
      effect of deadtime and scatter on accuracy in quantitation on a current PET
      system. Deadtime correction factors were found to be significant (1.1-2.5) at
      count rates found in clinical studies. Deadtime correction techniques were found
      to be accurate to within 5%. Scatter in emission and attenuation correction data
      consistently caused 5-15% errors in quantitation, whereas correction for scatter
      in both types of data reduced errors in accuracy to less than 5%.

PMID- 1997483
TI  - The precision of positron emission tomography: theory and measurement.
AB  - The limits of quantitation with positron emission tomography (PET) are examined
      with respect to the noise propagation resulting from radioactive decay and other
      sources of random error. Theoretical methods for evaluating the statistical error
      have been devised but seldom applied to experimental data obtained on human
      subjects. This paper extends the analysis in several ways: (1) A Monte Carlo
      method is described for tracking the propagation of statistical error through the
      analysis of in vivo measurements; (2) Experimental data, obtained in phantoms,
      validating the Monte Carlo method and other methods are presented; (3) A
      difference in activation paradigm, performed on regional CBF (rCBF) data from
      five human subjects, was analyzed on 1.6-cm diameter regions of interest to
      determine the mean fractional statistical error in PET tissue concentration and
      in rCBF before and after stereotactic transformation; and (4) A linear
      statistical model and calculations of the various statistical errors were used to
      estimate the magnitude of the subject-specific fluctuations under various
      conditions. In this specific example, the root mean squared (RMS) noise in flow
      measurements was about three times higher than the RMS noise in the concentration
      measurements. In addition, the total random error was almost equally partitioned
      between statistical error and random fluctuations due to all other sources.

PMID- 1997484
TI  - Absolute quantitation in neurological PET: do we need it?
AB  - This article addresses the question posed in the title by examining the effects
      of parameters traditionally associated with improved absolute quantitation, on
      the analysis of 12 acquired immune deficiency syndrome dementia complex (ADC)
      patients compared to a normal control group. Results are discussed within the
      framework of the subprofile scaling model (SSM) for analyzing patterns of
      regional covariation. It is demonstrated that the ability to extract measures of
      group discrimination and disease progression are unaffected by (1) limited
      improvements in image resolution, (2) the use of transmission scan smoothing, (3)
      the application of a scatter deconvolution correction, and (4) converting region
      of-interest measurements of counts per voxel to measurements of regional CMRglc.
      This "robustness" of the SSM approach is partly due to the extraction of disease
      related subject weights, independent of any subject's global scaling effects. It
      is argued that other analysis techniques that initially reduce intersubject
      variation (e.g., using regional ratios or normalizing by global metabolic rates
      before applying traditional multivariate procedures) lack analytic features that
      may be important to identify multidimensional, disease-related image patterns.
      Based on the ADC patient data, it is concluded that measures of group
      discrimination and disease progression will not necessarily benefit from the
      organization of parameters traditionally associated with improved absolute
      quantitation.

PMID- 1997485
TI  - The effects of collimation on PET image noise due to scatter, random counts, and
      deadtime.
AB  - The rates for true coincident events, scattered events, and singles in a Positron
      Emission Tomograph (PET) depend on the collimator size and shape. Monte Carlo
      techniques were used to compare efficiencies for wanted and unwanted events in
      multislice PET (MS-PET) and open collimator positron volumetric imaging (PVI)
      configurations. All systems used cylindrical arrays of bismuth germanate (BGO) or
      NaI crystals 51 cm in diameter and 10 cm deep suitable for whole brain imaging.
      The PVI systems detect about five times more true coincident events at low
      activity concentrations, but their scatter fraction is about three times higher.
      They are also much more sensitive to activity outside the scan field. As well as
      causing random counts when they fell within the energy acceptance window, single
      events are the main cause of deadtime. When the detectors are made from light
      encoded blocks deadtime is the major limitation at high count rates. When
      discrete crystals are used, the efficiency is lower and the random count rates
      are a more significant source of noise. Noise-effective count rates are used to
      compare the relative cost in system performance among different systems and
      sources of noise.

PMID- 1997486
TI  - Factors affecting accuracy and precision in PET volume imaging.
AB  - Volume imaging positron emission tomographic (PET) scanners with no septa and a
      large axial acceptance angle offer several advantages over multiring PET
      scanners. A volume imaging scanner combines high sensitivity with fine axial
      sampling and spatial resolution. The fine axial sampling minimizes the partial
      volume effect, which affects the measured concentration of an object. Even if the
      size of an object is large compared to the slice spacing in a multiring scanner,
      significant variation in the concentration is measured as a function of the axial
      position of the object. With a volume imaging scanner, it is necessary to use a
      three-dimensional reconstruction algorithm in order to avoid variations in the
      axial resolution as a function of the distance from the center of the scanner. In
      addition, good energy resolution is needed in order to use a high energy
      threshold to reduce the coincident scattered radiation.

PMID- 1997487
TI  - Precision and accuracy considerations of physiological quantitation in PET.
AB  - The ability to differentiate regional patterns of flow and metabolism between
      various patient populations depends upon the signal-to-noise characteristics of
      the data. The approach chosen for producing quantitative data will affect the
      detection sensitivity of a method. Methods based on mathematical models can
      reduce intersubject variability by accounting for factors unrelated to the
      physiological measure of interest, in particular, differences in the input
      function. However, errors in the model and in the implementation of a model-based
      method can increase variability compared to simpler, empirical methods.
      Normalization of physiological measures can significantly reduce intersubject
      variation; however, interpretation of normalized results can be more complex. The
      advantages and disadvantages of various approaches for physiological quantitation
      are considered.

PMID- 1997488
TI  - Region of interest issues: the relationship between structure and function in the
      brain.
AB  - The comparison of data sets from individual subjects between imaging modalities
      is necessary in order to evaluate the normal physiologic responses of the brain
      or the pathophysiological changes that accompany disease states. Similarly, it is
      critical to compare data between individuals both within and across imaging
      modalities. In a collaborative project with a number of university groups, we
      have developed a system that allows for the within-subject alignment and
      registration of three-dimensional data sets obtained from different modalities
      for the same individuals. These data make use of proposed criteria for the
      optimal solution to positron emission tomography image acquisition and analysis
      originally established through a series of international workshops. The analysis
      takes into account errors induced by image acquisition, registration, and
      alignment with regard to scaling, translation, and rotation. Using the principles
      of morphometrics and homologous landmarks, the between-subject warping of
      individual brain anatomy to match that of other individuals, groups or an
      idealized model can be obtained. Resultant information can provide averaged
      between-subject data for populations of normal individuals or patients with
      specific neurologic disorders. Such a system, provides the means by which to
      compare objectively quantitative data between individuals in a highly automated
      fashion.

PMID- 1997489
TI  - Quantitative comparison of measurements of cerebral glucose metabolic rate made
      with two positron cameras.
AB  - The rapid progress in PET technology has created the dilemma of how to compare
      data from old and new tomographs. We examined cerebral metabolic data from two
      scanners, with different spatial resolutions and methods of attenuation
      correction, to see if metabolic values from the lower-resolution tomograph (ECAT
      II) could be adjusted to make them comparable to data from the higher-resolution
      scanner (Scanditronix PC1024-7B). Nine subjects were scanned on both tomographs
      after a single injection of [18F]2-fluoro-2-deoxy-D-glucose. Regional and lobar
      gray matter metabolic rates for glucose were obtained from comparable images from
      each scanner. Ratios of lobar to global gray matter metabolism also were
      calculated. Regression coefficients and percent differences were computed to
      compare ECAT II and PC1024 data. Two-thirds of the region pairs showed
      significant regressions, although percent differences were quite variable, with
      measures of glucose utilization ranging from 30 to 120% higher on the PC1024
      compared to those from the ECAT II. Comparisons of lobar glucose rates between
      the two machines were less variable (50 to 80%), and ratios differed by only +/-
      5% (except for the temporal ratios). Since there was no simple and consistent
      relationship between regional metabolic rates on the two tomographs, an overall
      adjustment of regional ECAT values for comparison to PC1024 values would be
      impossible. A region-by-region adjustment would be necessary. Lobar ratios are
      sufficiently similar that direct comparisons might be possible.

PMID- 1997490
TI  - Specification and selection of regions of interest (ROIs) in a computerized brain
      atlas.
AB  - The computerized individually adjustable brain atlas (CBA) has been further
      developed. The atlas was primarily designed for anatomical localization and
      quantitative evaluation of data in positron emission tomography (PET), but may
      also be employed for other neuroimaging modalities, such as transmission computed
      tomography (CT) and magnetic resonance imaging (MRI). The atlas is based on
      anatomical information obtained from digitized cryosectioned brains. Using
      spatially standardized and then averaged MRI images, we demonstrate the high
      localization accuracy and precision of the brain atlas. This is a prerequisite
      for obtaining accuracy when using the atlas in the localization and the
      quantitative evaluation of PET data. The specification and the selection of
      region of interests (ROIs) by the CBA are presented and discussed.

PMID- 1997491
TI  - MRI-PET correlation in three dimensions using a volume-of-interest (VOI) atlas.
AB  - Quantitative interpretation of functional images (PET or SPECT) is hampered by
      poor spatial resolution, low counting statistics, and, for many tracers, low
      contrast between different brain structures of interest. Furthermore, normal
      tracer distributions can be severely disrupted by such gross pathologies as
      stroke, tumor, and dementia. Hence, the complementary anatomical information
      provided by CT or MRI is essential for accurate and reproducible regional
      analysis of functional data. We have developed methods for the simultaneous three
      dimensional display and analysis of image volumes from MRI and PET. A general
      algorithm for defining the affine transformation between two equivalent point
      ensembles has been adapted for the purpose of registering MRI and PET image
      volumes by means of a simple fiducial arrangement. In addition, we have extended
      previous MRI-based computerized atlas methodology to three dimensions. The native
      atlas planes were spaced at 2 mm intervals, sufficient axial sampling to permit
      the generation of oblique planar sections through the atlas space. This will
      allow for an infinite number of angulations and axial offsets in two-dimensional
      region-of-interest (ROI) templates, all derived from the same master three
      dimensional volume-of-interest (VOI) atlas and therefore maintaining
      topographical consistency throughout. These ROI templates may be selected to
      match the image orientation for conventional two-dimensional segmentation and
      data extraction.

PMID- 1997492
TI  - Physiological ROI definition by image subtraction.
AB  - Quantitative analysis of functional images requires a strategy for reducing to
      tractable size the overwhelming amount of numeric data contained therein. Region
      of-interest (ROI) selection is the most widely used means of image-data
      reduction, but it has many limitations. Spatial bias, introduced by selection of
      regions as being "of interest," is probably the greatest limitation of ROI
      analyses. Change-distribution analysis is a new data-analysis strategy that
      eliminates this a priori selection bias in a way that can increase the
      sensitivity, specificity, and localization precision. All image pixels are
      surveyed for changes from the control condition. Only areas of change are sampled
      and contribute to statistical analysis. Change-distribution analysis has been
      validated for within-subject pairs of images, but it is potentially applicable in
      a wide variety of imaging protocols.

PMID- 1997493
TI  - Effects of percent thresholding on the extraction of [18F]fluorodeoxyglucose
      positron emission tomographic region-of-interest data.
AB  - Although we and others have employed a thresholding strategy to extract "peak"
      values from positron emission tomographic (PET) regions of interest (ROIs), the
      effects of peak picking on fitted fluorodeoxyglucose rate constants, regional
      metabolic rate for glucose (rCMRglc) profiles, patterns of regional metabolic
      covariation, and PET-neurobehavioral correlations have not been systematically
      investigated. Our results suggest that under some commonly encountered imaging
      conditions percent thresholding may increase sensitivity to regional activation;
      however, the effect of thresholding is determined by a number of factors,
      including the relative magnitude of regional activation, ROI size, and the
      specific threshold selected. The difference-annulus concept is proposed as a
      means to study the effects of different region drawing and thresholding
      strategies, and to determine if a given ROI contains one and only one source of
      covarying metabolic activity.

PMID- 1997494
TI  - Statistical issues in the analysis of neuroimages.
AB  - Statistical issues in the analysis of neuroimages are reviewed. These include
      biological questions of interest, basic problems of measurement and experimental
      design, normalisation, standardisation and transformation, and statistical
      methodology. Finally, three data sets are reviewed to illustrate some of the
      issues raised in the report.

PMID- 1997495
TI  - Modeling the dependence of hexose distribution volumes in brain on plasma glucose
      concentration: implications for estimation of the local 2-deoxyglucose lumped
      constant.
AB  - The steady-state distribution volumes of glucose, 3-O-methylglucose, and 2
      deoxyglucose (2DG) are known to change as the concentration of glucose in plasma
      ranges from hypo- to hyperglycemic values. Model estimates of the three
      distribution volumes were compared with distribution volume values experimentally
      measured in the brains of conscious rats as the concentration of glucose in
      plasma was varied from 2 to 28 mM. The dependence on plasma glucose concentration
      of the 2DG lumped constant, the factor that relates the phosphorylation rate of
      2DG to the net rate of glucose utilization at unit specific radioactivity in the
      plasma, had been determined previously in separate series of experiments. The
      model was extended to incorporate this dependence of the lumped constant. In the
      model both the transport and the phosphorylation barriers were assumed to be
      single and saturable. The values of their respective half-saturation
      concentrations and the ratio of the two maximum velocities for glucose were
      assumed to be invariant over the entire range of plasma glucose concentration.
      Good agreement between measured and estimated values for the distribution volumes
      and the lumped constant was attained over the full range of plasma glucose
      concentration. The model estimates reflected the progressive transport limitation
      of the brain glucose content as plasma glucose levels were reduced to
      hypoglycemic values. The results also indicated that these changes should be
      evident in the time course of 2DG in brain following administration by bolus or
      continuous infusion, and thus that indexes of local lumped constant change could
      be derived from the time course data.

PMID- 1997496
TI  - PET measured evoked cerebral blood flow responses in an awake monkey.
AB  - We have developed a method to measure task-related regional cerebral blood flow
      (BF) responses in an awake, trained monkey using positron emission tomography
      (PET) and H215O. We trained an animal with operant conditioning using only
      positive reinforcement to climb unassisted into a modified primate chair that was
      then positioned in the PET scanner. A special headholder and acrylic skull cap
      permitted precise placement and accurate repositioning. We measured BF
      qualitatively with bolus injection of H215O and 40-s scan. Each session included
      scans at rest interposed with scans during vibration of a forepaw. Regional
      responses were identified using subtraction image analysis. After global
      normalization, a resting image was subtracted on a pixel-by-pixel basis from a
      comparable image collected during vibration. The region of peak response occurred
      in contralateral sensorimotor cortex with a mean magnitude of 11.6% (+/- 3.2%) of
      the global mean value for 10 separate experiments, significantly greater than the
      mean qualitative BF change (0.4 +/- 3.6%; p less than 0.00001) in the same region
      for seven rest-rest pairs. This newly developed technique forms the basis for a
      wide variety of experiments.

PMID- 1997497
TI  - Acetylcholine levels and choline acetyltransferase activity in rat
      cerebrovascular bed after uni- or bilateral sphenopalatine ganglionectomy.
AB  - Endogenous acetylcholine (ACh) levels and choline acetyltransferase (ChAT)
      activity were measured in several vascular segments (major cerebral arteries,
      cortical pial vessels, and peripheral arteries) and nervous tissues [including
      the sphenopalatine ganglion (SPG)] in the rat. The effects of uni- or bilateral
      surgical ablation of the SPG, a putative origin of the cholinergic
      cerebrovascular innervation, were investigated on these two specific cholinergic
      markers at various postoperative times. ChAT activity and ACh levels were
      enriched in the cerebral as compared to the peripheral arteries. Among the
      cerebrovascular tissues tested, ACh levels were particularly high in the circle
      of Willis and the vertebrobasilar segments and, to a lesser extent, in the middle
      cerebral artery. Lower levels were found in the small pial vessels and choroid
      plexus. Overall, ChAT activity measured in different arterial beds paralleled the
      distribution of ACh. Following uni- or bilateral removal of the SPG, slight
      reductions (18-36%, statistically not significant) were observed in ChAT activity
      in rostral cerebral arteries and pial vessels overlying the frontal cortex.
      Similarly, bilateral ganglionectomy resulted in minor decreases (11-22%, not
      significant) in the cerebrovascular contents of ACh in these same vascular
      segments. These results clearly show that the SPG does not or only partly
      contributes to the cholinergic fibers that supply the cerebrovascular bed.

PMID- 1997498
TI  - Regional cerebral metabolites, blood flow, plasma volume, and mean transit time
      in total cerebral ischemia in the rat.
AB  - Cerebral high-energy metabolites and metabolic end products were measured during
      and following total cerebral ischemia in the rat. During cerebral ischemia,
      lactate accumulation was greatest in the hippocampus, followed by the cerebral
      cortex and striatum. Following reperfusion, the rate of lactate clearance was
      slower in the hippocampus than in the other two regions. Regional CBF, cerebral
      plasma volume (CPV), and calculated mean transit time (MTT) were determined
      following reflow of ischemic tissue. During hyperemia, CPV, used as an indicator
      of capillary volume, increased concomitantly with CBF while the MTT remained near
      the control value, suggesting that the linear flow rate through the vasculature
      was unchanged. During hypoperfusion, CPV returned to control values, but there
      was a significant increase in MTT that would result from a decreased linear
      velocity. The finding of normal tissue energy charge, pHi, and concentration of
      other metabolites during hypoperfusion shows that hypoperfusion does not result
      in CBF-metabolic mismatch.

PMID- 1997499
TI  - Autoradiographic analysis on second-messenger systems and local cerebral blood
      flow in ischemic gerbil brain.
AB  - Alterations of the second-messenger systems, adenylate cyclase (AC) and protein
      kinase C (PKC), and local cerebral blood flow (lCBF) were evaluated during
      experimental cerebral ischemia in gerbils employing a quantitative
      autoradiographic method, which permitted these three parameters to be measured in
      the same brain. Ischemia was induced by occlusion of the right common carotid
      artery for 6 h. Animals attaining more than 5 in their ischemic scores were
      utilized for further experiments. At the end of ischemia, lCBF was measured by
      the [14C]iodoantipyrine method. The AC and PKC activities were estimated by the
      autoradiographic technique developed in our laboratory using [3H]forskolin (FK)
      and [3H]phorbol-12,13-dibutyrate (PDBu), respectively. The lCBF fell below 10
      ml/100 g/min in most cerebral regions on the ligated side. The greatest reduction
      in FK binding was noted in the olfactory tubercle, caudate-putamen, and globus
      pallidus, followed by the hippocampus and cerebral cortices. The FK binding
      tended to be low at lCBF less than 20 ml/100 g/min in the cerebral cortices.
      However, the PDBu binding was relatively well preserved in each cerebral
      structure, and no significant correlation between lCBF and PDBu binding was noted
      in the cerebral cortices. The AC system may thus be vulnerable to ischemic insult
      over extensive brain regions, while the PKC system may be relatively resistant to
      ischemia.

PMID- 1997500
TI  - Sex differences in postischemic neuronal necrosis in gerbils.
AB  - Twenty-four hour postischemic neuronal necrosis was compared in male vs. female
      Mongolian gerbils subjected to a 3-h period of severe incomplete hemispheric
      ischemia produced by unilateral carotid occlusion. The incidence of stroke-prone
      males was 42.9% versus 26.7% for the females. Among the stroke-prone animals, the
      males displayed significantly greater neuronal necrosis at 24 h after ischemia
      compared to the females in the cerebral cortex and CA1 region of the hippocampus.
      In the CA1 region of the stroke-prone males, only 2.0% of the normal neuronal
      population remained by 24 h compared to 36.8% in the stroke-prone females (p less
      than 0.02). In the cerebral cortex, the males had only 19.9% of normal versus
      58.2% in the females (p less than 0.05). In a second series of mechanistic
      experiments, no differences in cortical blood flow (CBF) were disclosed between
      preselected male and female stroke-prone animals before, during, or for 2 h after
      ischemia. As with the CBF, the extent of cortical extracellular hypocalcia during
      ischemia did not differ significantly. However, the degree of postischemic
      recovery of cortical extracellular calcium was significantly better in the
      females from 30 min to 2 h after reperfusion. In the same experiments,
      hemispheric vitamin E levels were measured at the 2 h time point as an index of
      postischemic brain lipid peroxidation. No difference in baseline vitamin E levels
      was observed between male and female sham-operated gerbils. In the males
      subjected to 3 h of ischemia plus 2 h of reperfusion, the hemispheric vitamin E
      decreased by 43.5% compared to the sham-operated males.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1997501
TI  - Induced tolerance to ischemia in gerbil hippocampal neurons.
AB  - Brief ischemia induced tolerance to subsequent ischemia in the hippocampal
      neurons. Male Mongolian gerbils were subjected to 2 min of ischemia in an awake
      condition. This ischemic insult only rarely produced neuronal damage in the
      gerbil brain. One day (n = 9), 2 days (n = 9), or 4 days (n = 10) following the
      first brief ischemia, the animals (double-ischemia group) were subjected to the
      second ischemia for 5 min. The single-ischemia group received a sham procedure
      instead of the first ischemia and was identically subjected to the second
      ischemia 1 day (n = 9), 2 days (n = 10), and 4 days (n = 13) following the sham
      procedure. One week following the second ischemia, all gerbils were perfusion
      fixed and the neuronal density in the hippocampal CA1 sector was measured. In
      double-ischemia groups, the neuronal density per 1-mm length of the pyramidal
      cell layer was 103.4 +/- 93.1 (SD) in the 1-day subgroup, 125.6 +/- 64.2 in the 2
      day subgroup, and 176.2 +/- 93.7 in the 4-day subgroup, while the density in
      normal gerbils was 254.7 +/- 18.6. The average neuronal density in the single
      ischemia group was much lower than that in the double-ischemia group (whole
      control group: 10.9 +/- 27.4). Immunostaining using monoclonal antibody raised
      against 70-kDa heat-shock protein revealed an increase in 70-kDa heat-shock
      protein in the CA1 area following 2 min of ischemia. Very brief ischemia induces
      heat-shock proteins and, presumably, thereby renders neurons more tolerant to
      subsequent metabolic stress.

PMID- 1997502
TI  - Formation of free choline in brain tissue during in vitro energy deprivation.
AB  - Free choline and ATP contents were measured in Mongolian gerbil hippocampal
      slices (tissue) and incubation media (media) during exposure to 30 min of
      aglycemia, high potassium, anoxia, or ischemia. Changes in choline levels
      reflected the degree of energy reduction, lower ATP levels being associated with
      high choline (4-fold increase during exposure to high potassium and anoxia, and
      11-fold increase during ischemia). Media (extracellular) choline was particularly
      affected and increased about twofold during relatively mild energy depletion
      (e.g., aglycemia), but tissue choline content was less sensitive to energy
      reduction. A plot of choline vs. ATP levels indicated a nonlinear correlation,
      and the sharp increase in choline occurred when ATP values fell to about 2.5
      nmol/mg of protein. Inhibition of acetylcholine sterase by 10 microM
      physostigmine during ischemia did not prevent an increase in choline contents but
      rather enhanced them, indicating that acetylcholine hydrolysis was not the source
      of free choline. Formation of free choline was Ca2+ independent. These findings
      suggest the involvement of phospholipase D and phosphatidylcholine hydrolysis in
      free choline formation during energy stress. The extent of choline formation may
      be an indicator of the degree of membranal damage, which in turn reflects damage
      to the metabolic machinery of the cell.

PMID- 1997503
TI  - Macrophage and astrocyte populations in relation to [3H]PK 11195 binding in rat
      cerebral cortex following a local ischaemic lesion.
AB  - PK 11195 is a selective and specific ligand for the peripheral-type
      benzodiazepine binding site. Its potential for in vivo visualisation of lesioned
      human brain using positron emission tomography (PET) is currently being assessed.
      The present study examines the relationship between the temporal development of a
      local ischaemic lesion with its associated cell populations and the binding of
      [3H]PK 11195 in rat brain. Unilateral cortical infarcts were induced using the
      photosensitive dye Rose Bengal. At time intervals from 1 to 7 days after
      lesioning, the localisation of [3H]PK 11195 binding was determined using in vivo
      and in vitro autoradiography. Sections adjacent to those used for autoradiography
      were processed for immunohistochemistry using glial fibrillary acidic protein for
      astrocytes and ED-1 for macrophages. The results show that the binding of [3H]PK
      11195 correlates in both time and spatial localisation with the appearance of
      macrophages around the lesion. Reactive astrocytes, although present, occupy a
      separate region in the tissue surrounding the lesion and lie outside the region
      defined by the [3H]PK 11195 binding. We conclude that the [3H]PK 11195 signal
      associated with this ischaemic lesion originates primarily from binding to
      macrophages and that [11C]PK 11195 could be used for imaging acute inflammatory
      response in human brain using PET.

PMID- 1997504
TI  - Diminished glucose transport in Alzheimer's disease: dynamic PET studies.
AB  - Dynamic positron emission tomography with [18F]fluorodeoxyglucose was used in six
      patients with Alzheimer's disease (AD) and seven healthy age-matched control
      subjects to estimate the kinetic parameters K1*, k2*, and k3* that describe
      glucose transport and phosphorylation. A high-resolution tomograph was used to
      acquire brain uptake data in one tomographic plane, and a radial artery catheter
      connected to a plastic scintillator was used to acquire arterial input data. A
      nonlinear iterative least-squares fitting procedure that included terms for the
      vascular fraction and time delay to the peripheral sampling site was used to fit
      a three-compartment model to the brain data. Regions studied included frontal,
      temporal, occipital, and the entire cortex and subcortical white matter. The
      values obtained for the individual rate constants and regional CMRglc (rCMRglc;
      calculated using regional values of the rate constants) were higher than those
      reported previously. A significant (p less than 0.05) decrease was found in K1*
      in frontal and temporal cortex in the AD patients compared with the controls,
      with values of 0.157 and 0.161 ml/g/min in frontal and temporal cortex,
      respectively, of controls and 0.127 and 0.126 ml/g/min in frontal and temporal
      cortex of the AD patients. rCMRglc was also significantly (p less than 0.02)
      lower in the AD patients than controls in all cortical brain regions. Lower
      values of k3* were found in all brain regions in the AD patients, although these
      were not statistically significant. These findings provide evidence of an in vivo
      abnormality of forward glucose transport in AD.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1997505
TI  - Altered cerebral blood flow and glucose metabolism in patients with liver disease
      and minimal encephalopathy.
AB  - We measured CBF and the CMRglc in normal controls and in patients with severe
      liver disease and evidence for minimal hepatic encephalopathy using positron
      emission tomography. Regions were defined in frontal, temporal, parietal, and
      visual cortex; the thalamus; the caudate; the cerebellum; and the white matter
      along with a whole-slice value obtained at the level of the thalamus. There was
      no difference in whole-slice CBF and CMRglc values. Individual regional values
      were normalized to the whole-slice value and subjected to a two-way repeated
      measures analysis of variance. When normalized CBF and CMRglc values for regions
      were compared between groups, significant differences were demonstrated (F =
      5.650, p = 0.00014 and F = 4.58, p = 0.0073, respectively). These pattern
      differences were due to higher CBF and CMRglc in the cerebellum, thalamus, and
      caudate in patients and lower values in the cortex. Standardized coefficients
      extracted from a discriminant function analysis permitted correct group
      assignment for 95.5% of the CBF studies and for 92.9% of the CMRglc studies. The
      similarity of the altered pattern of cerebral metabolism and flow in our patients
      to that seen in rats subjected to portacaval shunts or ammonia infusions suggests
      that this toxin may alter flow and metabolism and that this, in turn, causes the
      clinical expression of encephalopathy.

PMID- 1997506
TI  - Cerebral ammonia metabolism in patients with severe liver disease and minimal
      hepatic encephalopathy.
AB  - Cerebral ammonia metabolism was studied in five control subjects and five
      patients with severe liver disease exhibiting minimal hepatic encephalopathy. The
      arterial ammonia concentration in the control subjects was 30 +/- 7 mumol/L (mean
      +/- SD) and 55 +/- 13 mumol/L in the patients (p less than 0.01). In the normal
      subjects, the whole-brain values for cerebral blood flow, cerebral metabolic rate
      for ammonia, and the permeability-surface area product for ammonia were 0.58 +/-
      0.12 ml g-1 min-1 0.35 +/- 0.15 mumol 100 g-1 min-1, and 0.13 +/- 0.03 ml g-1 min
      1, respectively. In the patients, the respective values were 0.46 +/- 0.16 ml g-1
      min-1 (not different from control), 0.91 +/- 0.36 mumol 100 g-1 min-1 (p less
      than 0.025), and 0.22 +/- 0.07 ml g-1 min-1 (p less than 0.05). The increased
      permeability-surface area product of the blood-brain barrier permits ammonia to
      diffuse across the blood-brain barrier into the brain more freely than normal.
      This may cause ammonia-induced encephalopathy even though arterial ammonia levels
      are normal or near normal and explain the emergence of toxin hypersensitivity as
      liver disease progresses. Greater emphasis on early detection of encephalopathy
      and aggressive treatment of minimal hyperammonemia may retard the development of
      ammonia-induced complications of severe liver disease.

PMID- 1997507
TI  - The effect of stable xenon on ICP.
AB  - Recent studies have suggested that under certain conditions, inhalation of stable
      xenon can cause an increase in CBF or intracranial pressure (ICP). We reviewed
      the ICP changes that occurred during 48 stable xenon/CT CBF studies in 23
      comatose head-injured patients to determine if the concentration (32%) and
      duration of inhalation (4.5 min) of stable xenon we used caused an increase in
      ICP. In the group as a whole, there was no significant difference between the
      mean ICP at the start of xenon inhalation and the mean ICP immediately after
      completion of the studies. An increase in ICP also was not found in subgroups
      with low, normal, or high global CBF, or groups with or without intracranial
      hypertension. Changes in ICP that occurred during individual studies usually were
      related to corresponding changes in the arterial pCO2 (p less than 0.0001,
      Pearson's correlation test). Our data suggest that 32% stable xenon administered
      for 4.5 min does not cause a significant increase in ICP during xenon/CT CBF
      studies.

PMID- 1997508
TI  - Clinical review 19: Management of congenital hypothyroidism.

PMID- 1997509
TI  - Differential effects of inhaled budesonide and oral prednisolone on serum
      osteocalcin.
AB  - Inhaled glucocorticosteroids have been developed for the treatment of asthma in
      an attempt to minimize the suppression of endogenous adrenal function that
      complicates oral or injected steroid usage, but it is unclear whether this
      strategy leads to reduced systemic complications in other areas, such as the
      skeleton. In this study we evaluated serum osteocalcin levels as a marker of
      skeletal metabolism in healthy volunteers treated with oral and inhaled steroids
      alone and in response to an oral calcitriol stimulation test. Forty subjects,
      aged 33 +/- 9 (mean +/- SD) yr were randomized to receive either high or low dose
      oral prednisolone (40 vs. 10 mg/day) or inhaled budesonide (3.2 vs. 0.8 mg/day).
      Each dose of budesonide is known to have a greater antiasthmatic potency than the
      dose of prednisolone with which it was compared. In addition 10 control subjects
      received placebos containing no active steroid drugs. During the second week of
      treatment, half of the subjects in each of the 4 steroid-treated groups and all
      subjects in the control group received oral calcitriol (2.0 micrograms/day).
      There was a marked dose-dependent reduction in serum cortisol levels, but this
      reduction was significantly less pronounced during budesonide treatment, such
      that low dose budesonide was without effect. During the first week of steroid
      therapy there were significant dose-dependent reductions in serum osteocalcin (P
      = 0.003), but this reduction was not significantly different between budesonide
      and prednisolone treatments. In response to calcitriol, serum osteocalcin
      increased by 35% in the control group (P = 0.06). Osteocalcin levels increased by
      56% and 50% in the low dose budesonide and prednisolone groups and by 106% in the
      high dose budesonide group, but did not change in the high dose prednisolone
      group. The osteocalcin response to calcitriol was significantly higher in the
      budesonide groups (P = 0.03, by analysis of variance). High dose prednisolone
      caused increases in serum 1,25-dihydroxyvitamin D3 (P less than 0.02), urinary
      calcium excretion (P = 0.07), and urinary hydroxyproline (P less than 0.01). None
      of these changes was seen during budesonide therapy. There are as yet no data for
      these variables after long term use of inhaled budesonide in asthmatic patients,
      but our acute studies suggest that this potent topical glucocorticoid may have
      considerably less impact on the skeleton than oral prednisolone, even if used at
      doses high enough to suppress endogenous adrenal function.

PMID- 1997510
TI  - Plasma intact parathyroid hormone (PTH) and PTH-related peptide in familial
      benign hypercalcemia: greater responsiveness to endogenous PTH than in primary
      hyperparathyroidism.
AB  - The cause of hypercalcemia in familial benign hypercalcemia (FBH; also called
      familial hypocalciuric hypercalcemia) is unclear, although it is PTH dependent.
      It is also uncertain how plasma PTH levels are related to the severity of
      biochemical abnormalities in FBH. Because the PTH-related peptide (PTHrP) has
      many PTH-like actions, it might have a role in the hypercalcemia of FBH. Thus, we
      studied 29 patients with FBH from 11 families, 29 age- and sex-matched controls,
      and 42 patients with primary hyperparathyroidism (1 degree HPT), measuring PTH
      with a highly sensitive two-site immunochemiluminometric assay and the
      hypercalcemic tumor factor PTH-related peptide (PTHrP) with an
      extraction/concentration RIA. Plasma PTH values were elevated in 86% of 1 degree
      HPT patients (36 of 42), but in only 20% of FBH patients, (6 of 29). Plasma PTHrP
      was elevated in 1 FBH patient, and the group mean value was normal. Plasma PTH
      was positively correlated with calcium (Ca) in 1 degree HPT (r = 0.66; P less
      than 0.0001) and in FBH (r = 0.53; P less than 0.004), but the slopes of the
      regressions were markedly different: 1 degree HPT, 6.72; FBH, 1.61 (P less than
      0.0001). There was a negative correlation between PTH and phosphorus (P) in 1
      degree HPT (r = -0.39; P less than 0.01) and in FBH (r = -0.41; P less than
      0.03), but, again, the slopes differed greatly: 1 degree HPT, -6.57; FBH, -1.95
      (P less than 0.0001). There were no correlations between PTHrP and Ca or between
      PTH and PTHrP. The sums and products of PTH and PTHrP were not better correlated
      with Ca than PTH alone. Thus, PTH values are lower at given Ca and P levels in
      patients with FBH than in those with 1 degree HPT, suggesting that PTH is more
      effective in raising Ca and lowering P in FBH than in 1 degree HPT. The enigma of
      FBH remains: what molecular defect can simultaneously cause parathyroid cell
      insensitivity to Ca, enhanced renal tubular reabsorption of Ca, increased renal
      rejection of P, and enhanced or retained sensitivity to PTH?

PMID- 1997511
TI  - Dexamethasone-nonsuppressible cortisol in two cases with aldosterone-producing
      adenoma.
AB  - Forty-one patients with aldosterone-producing adenoma (APA) were subjected to a
      dexamethasone suppression test (DST) before surgery. Serum cortisol and urinary
      excretion of 17-hydroxycorticosteroids were suppressed by dexamethasone in 39
      patients [DST(+)]. In two patients (cases A and B), they were not suppressed
      [DST(-)]. Clinical manifestations of the two DST(-) patients were similar to
      those of DST(+) patients. Hypertension, hypokalemia, high serum aldosterone
      levels, and suppressed PRA were found in all of the patients. The cut surfaces of
      the adenomas from all of the patients, including cases A and B, were golden
      yellow, which is typical of APA. However, atrophies of the adjacent normal
      tissues were evident exclusively in the two DST(-) patients. After removal of the
      affected adrenals, the serum cortisol level was suppressed by dexamethasone in
      one of the DST(-) patients (case B). These findings suggested autonomous cortisol
      production by APA. To evaluate whether cortisol could be produced from the
      adenoma tissue, the presence of several steroidogenic enzymes was studied by
      immunohistochemistry and mRNA analysis in the adenomas and the adjacent
      nonneoplastic adrenals from the 2 DST(-) and 5 DST(+) patients.
      Immunohistochemical analysis demonstrated that steroidogenic enzymes were
      expressed in APA tumor tissues from both DST(-) and DST(+) patients. In both
      groups, mRNAs coding steroidogenic enzymes were present not only in the
      nonneoplastic but also in the tumor tissues. Quantitative analysis of the mRNA
      levels revealed that in the adrenals from DST(+) patients, the mRNAs were more
      abundant in nonneoplastic tissue than in tumor tissue. However, in those from
      DST(-) cases, the mRNAs were much more abundant in the tumor tissues than in the
      nonneoplastic tissues. These results indicate that tumor cells of the two DST(-)
      patients autonomously synthesized not only aldosterone but also cortisol. The
      diameters of the tumors from the two DST(-) patients exceeded 3 cm, while those
      from other DST(+) patients were smaller. In patients with large APA, adrenal
      insufficiency should be anticipated upon removal of the tumor.

PMID- 1997512
TI  - Developmental pattern of urinary epidermal growth factor in the premature infant
      and the influence of gender.
AB  - We report the cross-sectional pattern of first day urinary epidermal growth
      factor/creatinine (EGF/Cr) levels in 159 appropriate for gestational age infants
      born at 26-41 weeks gestation. EGF/Cr levels rose significantly earlier in female
      infants than levels in male infants. In female infants levels were similar to
      term levels beginning at 30-32 weeks. Mean EGF/Cr levels in male infants were
      similar to term values beginning at 32-34 weeks. We could not demonstrate any
      influence from acute perinatal events on EGF/Cr levels. In a subset of 28
      infants, a weekly longitudinal study of urinary EGF/Cr levels was undertaken. The
      urinary EGF/Cr pattern correlated significantly with both corrected gestational
      and postnatal ages. A significant change in the EGF/Cr pattern was observed at a
      corrected gestational age of 32 weeks and at 4 weeks postnatal age. There was no
      significant difference in EGF/Cr levels between males and females. Our results
      demonstrated a significant difference in first day urinary EGF/Cr levels between
      female and male preterm infants during the early third trimester. This difference
      was seen at a time in gestation when other gender-specific maturational and
      growth differences are noted. When infants born at less than 32 weeks gestational
      age were followed longitudinally, the urinary EGF/Cr pattern, when expressed by
      corrected gestational age, was significantly modified from that in the cross
      sectional study.

PMID- 1997513
TI  - Trophoblast-derived interleukin-1 (IL-1) stimulates the release of human
      chorionic gonadotropin by activating IL-6 and IL-6-receptor system in first
      trimester human trophoblasts.
AB  - Interleukin-1 (IL-1) has a unique activity to stimulate the release of multiple
      hormones in a number of human and murine endocrine systems. IL-6 also expresses
      such activities by activating IL-6-receptor (R)-mediated signal transduction
      pathways. Since the placenta produces both of these cytokines and endocrine
      hormones such as hCG, we investigated how these cytokines regulate hCG release by
      normal trophoblasts. Trophoblasts purified by Percoll density gradient released
      hCG from 120 min after stimulation with recombinant (r) IL-1 alpha, and its
      release was dependent on the rIL-1 alpha concentration used. The rIL-1 alpha
      stimulated trophoblasts released a molecule with IL-6 activity antecedently, as
      determined by an IL-6-dependent cell line, MH60.BSF2 cells. The IL-6 identity of
      the released molecule was confirmed by goat anti-IL-6 antiserum. rIL-1-mediated
      hCG release from trophoblasts was completely abrogated to the basal level by
      pretreatment of the trophoblasts with PM1, an anti-IL-6-R monoclonal antibody.
      Identical results were observed with rIL-1 beta. These results showed that rIL-1
      induced hCG release was totally dependent on IL-6- and IL-6-R-mediated signal
      transduction in human trophoblasts. The presence of peripheral monocytes in the
      purified trophoblast fraction, however, induced a rapid decrease in IL-6 and hCG
      release after their maximal release, suggesting some regulatory interaction
      between trophoblasts and the monocytes. In contrast, rIL-1-mediated enhancement
      of IL-6 and hCG secretion by purified trophoblasts was no longer observed at 24 h
      compared with that of the unstimulated trophoblasts, while spontaneous hCG
      secretion was significantly inhibited by pretreatment of trophoblasts with PM1.
      The results showed that IL-6 and hCG secretion might also be regulated by a
      number of agents besides IL-1, and that hCG secretion as well as its release is
      dependent on IL-6 and IL-6-R system in trophoblasts.

PMID- 1997514
TI  - Recovery from osteopenia in adolescent girls with anorexia nervosa.
AB  - Osteopenia is a frequent complication of anorexia nervosa (AN). To determine
      whether the deficit in bone mineral changes during the course of this illness, we
      studied 15 adolescent patients prospectively for 12-16 months using dual photon
      absorptiometry of the spine and whole body. At follow-up, mean weight, height,
      and body mass index (BMI) had increased significantly, although 6 girls had
      further weight loss or minimal gain (less than 1.2 kg). Spontaneous menses
      occurred in 2 girls, and 3 others were given estrogen replacement. Bone mineral
      density of the lumbar spine did not change significantly (mean +/- SD, 0.836 +/-
      0.137 vs. 0.855 +/- 0.096 g/cm2), while whole body bone mineral density increased
      (0.710 +/- 0.118 vs. 0.773 +/- 0.105; P less than 0.05). Despite gains in bone
      mineral, 8 patients had osteopenia of the spine and/or whole body. Changes in
      weight, height, and BMI were significant predictors of change in bone mineral
      density. Increased bone mass occurred with weight gain before return of menses;
      conversely, weight loss was associated with further decreases in bone density. In
      1 patient who failed to gain weight, estrogen therapy resulted in increased
      spinal, but not whole body, bone mineral. We also studied a second group of 9
      women who had recovered from AN during adolescence. All 9 had normal whole body
      bone mineral for age, but 3 had osteopenia of the lumbar spine. We conclude that
      osteopenia in adolescents with AN reflects bone loss, perhaps combined with
      decreased bone accretion. Weight rehabilitation results in increased bone mineral
      before the return of menses. Estrogen may have an independent effect on bone
      mass. The persistence of osteopenia after recovery indicates that deficits in
      bone mineral acquired during adolescence may not be completely reversible.

PMID- 1997515
TI  - Pulsatile insulin delivery has greater metabolic effects than continuous hormone
      administration in man: importance of pulse frequency.
AB  - The aim of this study was to see if the greater effect of insulin on hepatic
      glucose output when insulin is given using 13-min pulses in man remains when the
      same amount of insulin is delivered using 26-min pulses. The study was performed
      on nine male healthy volunteers submitted to a 325 min glucose-controlled glucose
      iv infusion using the Biostator. The endogenous secretion of pancreatic hormones
      was inhibited by somatostatin. Three experiments were performed in each subject
      on different days and in random order. In all cases glucagon was replaced (58 ng
      min-1). The amounts of insulin infused were identical in all instances and were
      0.2 mU kg-1 min-1 (continuous), 1.3 mU kg-1 min-1, 2 min on and 11 min off (13
      min pulses) or 2.6 mU kg-1 min-1, 2 min on and 24 min off (26-min pulses). Blood
      glucose levels and glucose infusion rate were monitored continuously by the
      Biostator, and classic methodology using D-[3-3H] glucose infusion allowed to
      study glucose turnover. When compared with continuous insulin, 13-min insulin
      pulses induced a significantly greater inhibition of endogenous glucose
      production. This effect disappeared when insulin was delivered in 26-min pulses.
      We conclude that, in man, an adequate pulse frequency is required to allow the
      appearance of the greater inhibition of pulsatile insulin on endogenous glucose
      production.

PMID- 1997516
TI  - Human milk stimulates prostacyclin production by cultured human vascular
      endothelial cells.
AB  - Prostacyclin (PGI2) is an antithrombotic and vasodilatory factor, which is
      produced mainly by the vascular endothelium. Little is known about how this
      process is regulated. We investigated the effect of human milk on PGI2 synthesis
      by human vascular endothelial cells by measuring its stable metabolite, 6-keto
      prostaglandin F1 alpha, by RIA. Human milk induced dose- and time-dependent
      stimulation of PGI2 production, whereas cow's milk was ineffective. The lowest
      concentration of human milk that stimulated the production of PGI2 was 0.1%, and
      10% induced a 2.4- to 3.4-fold increase. The effect of human milk was detectable
      after 2 h and was blocked by inhibitors of transcription, translation, and
      cyclooxygenase. Boiling abolished the activity, but acetone extraction enhanced
      it. A 10% concentration of acetone-extracted human milk stimulated the release of
      endothelial cell PGI2 by 6.6-fold. In human milk samples we found no correlation
      between the amount of immunoreactive epidermal growth factor (EGF) and the
      activity stimulating PGI2 synthesis. Furthermore, EGF antibodies did not inhibit
      the activity. This is the first demonstration that human milk stimulates PGI2
      production by endothelial cells. We conclude that human milk is a potent inducer
      of PGI2 production by human vascular endothelial cells and that the stimulatory
      activity is not due to EGF.

PMID- 1997517
TI  - Subclinical vitamin D deficiency in postmenopausal women with low vertebral bone
      mass.
AB  - To define the potential role of subclinical vitamin D deficiency in
      postmenopausal bone loss, we analyzed the levels of circulating 25-hydroxyvitamin
      D (25OHD) in 539 midwestern caucasian women screened for osteoporosis. Low 25OHD
      (less than 38 nmol/L) was found in 49 subjects (aged 52-77 yr). Women with low
      25OHD had a reduced vertebral bone density (VBD), assessed by quantitative
      computed tomography, compared to age-matched controls (P less than 0.001). They
      also had significantly lower levels of serum calcium and phosphate, lower urinary
      calcium, higher serum alkaline phosphatase, and, in most cases, increased
      immunoreactive PTH (iPTH) concentrations, suggesting secondary
      hyperparathyroidism. Furthermore, only in the low 25OHD group did VBD correlate
      directly with 25OHD (r = 0.41; P less than 0.01), and inversely with iPTH (r = 
      0.47; P less than 0.01). Multivariate analyses revealed that iPTH was the major
      determinant of the observed decrease in VBD. Seasonal variations of serum 25OHD
      were noted only in the control population; in this group the 25OHD levels also
      correlated with sunlight exposure (r = 0.48; P less than 0.01), as assessed by an
      outdoor score. Thus, vitamin D deficiency develops when both the endogenous and
      exogenous sources are insufficient and contributes to a reduced bone mass in
      elderly women.

PMID- 1997518
TI  - A comparison of the efficacy and safety of pergolide and bromocriptine in the
      treatment of hyperprolactinemia.
AB  - Pergolide is a synthetic ergoline derivative with highly potent long-acting PRL
      lowering activity, allowing therapy of hyperprolactinemia with a once daily
      administration of the drug. The results of two open-label, randomized controlled
      multicenter clinical trials are reported. Pergolide (taken once a day), was
      compared with bromocriptine (taken two to four times daily) regarding efficacy
      and safety in the reduction of PRL levels, the cessation of galactorrhea and
      amenorrhea, the improvement in sexual function, and tumor shrinkage in
      hyperprolactinemia without (trial I; 61 patients) and with radiologically evident
      pituitary tumors (trial II; 96 patients). Both drugs were equally effective in
      lowering PRL levels in both trials. A median optimal dose of 50 micrograms
      pergolide and 5 mg bromocriptine/day suppressed PRL levels in the 61 patients of
      trial I by more than 80%. During the 24-week investigational period galactorrhea
      disappeared in 96% and 87% of patients, whereas menstruation returned in 90% and
      96% of patients, respectively. An equally high efficacy (optimal median dose: 75
      100 micrograms pergolide, 7.5-10 mg bromocriptine daily) was observed in trial
      II, although the resumption of menses was less frequent than in the patients of
      trial I (50% and 58% of patients, respectively). Sexual dysfunction improved
      similarly on both drugs in about half the patients. In addition, tumor shrinkage
      occurred to a similar extent with both drugs. A high incidence of adverse events
      was noted especially at the initiation of therapy with both compounds: nausea,
      dizziness, vomiting, asthenia, headache, and decrease in blood pressure occurred
      at a similar incidence and extent during the use of pergolide and bromocriptine.
      Patients in trial I treated with pergolide reported a slightly higher incidence
      of fever, vasodilatation, and flu syndrome. CONCLUSIONS: in these 24-week studies
      comprising a total of 157 hyperprolactinemic patients, a once daily
      administration of pergolide was shown to be as safe and effective as the two to
      four times daily ingestion of bromocriptine. Longer-acting dopamine agonists like
      pergolide that can be taken once daily, are likely to increase the ease to
      adherence to the therapeutic regimen. This might result in a higher compliance to
      medical treatment of hyperprolactinemia.

PMID- 1997519
TI  - Intravenous glucose tolerance test-derived insulin sensitivity changes during the
      menstrual cycle.
AB  - Using glucose tolerance tests or a glucose clamp some studies report impaired
      insulin sensitivity during the luteal phase of the menstrual cycle, while others
      find no change in insulin sensitivity. Tissue sensitivity to insulin and glucose
      effectiveness can be estimated using the minimal model analysis of an iv glucose
      tolerance test (IVGTT), but this method has never been applied to evaluate the
      impact of the menstrual cycle on these parameters. We, therefore, studied eight
      cycling women using tolbutamide-modified IVGTTs during three different phases of
      the same menstrual cycle: early follicular, midcycle, and midluteal. Insulin
      sensitivity (SI) and glucose effectiveness were derived using insulin and glucose
      levels obtained from tolbutamide-modified IVGTTs and analyzed with the minimal
      model computer program. The mean SI (x10(-4)/min.microU/mL) decreased in a
      stepwise fashion from the follicular level of 6.20 +/- 0.91 to a midcycle level
      of 4.95 +/- 0.73 and was lowest in the luteal phase (3.20 +/- 0.25; P less than
      0.007). No change in glucose effectiveness occurred as a function of the
      menstrual cycle. These findings indicate a significant decrease in insulin
      sensitivity in the luteal phase of the normal menstrual cycle, but no significant
      change at midcycle.

PMID- 1997520
TI  - Estrogen regulates the gonadotropin-releasing hormone-stimulated secretion of
      biologically active luteinizing hormone.
AB  - Estrogen produces time-dependent bidirectional effects on the GnRH-stimulated
      release of immunoactive LH in various species. To examine estrogen's regulation
      of biologically active LH secretion in response to pulsatile stimulation by GnRH,
      we studied estrogen-deficient postmenopausal women basally and during treatment
      with diethlystilbesterol (DES; 1 mg, orally, daily). Basal and GnRH-stimulated
      plasma concentrations of bioactive LH were assayed by the in vitro rat
      interstitial cell testosterone bioassay. GnRH-promoted LH secretory bursts in
      response to two consecutive stimuli were quantitated by multiple parameter
      deconvolution analysis. Basal half-lives of LH averaged 171 +/- 17 min
      (immunoactive) and 223 +/- 10 min (bioactive). Analysis of variance revealed a
      significant decrease in mean basal plasma bioactive LH concentrations on days 10
      and 30 of DES treatment. Mean serum immunoactive LH concentrations fell
      similarly. DES significantly increased the half-life of immunoactive LH (days 5
      and 10), but did not change that of bioactive LH. GnRH self-priming of bioactive
      LH secretion (increased LH secretory peak 2 compared to peak 1) was demonstrated,
      with a maximal value on day 10 of DES treatment. In addition, the ratio of the
      mass of bioactive to immunoactive LH secreted in response to the first GnRH pulse
      was significantly enhanced by estrogen on day 5, whereas that after the second
      pulse of GnRH was significantly suppressed on day 30 of DES. The self-priming
      action of GnRH on bioactive LH release evident in the presence of oral DES was
      corroborated in a separate group of six women, who were treated for 30 days with
      17 beta-estradiol via an intravaginally placed Silastic ring. In conclusion, we
      infer that estrogen exerts a highly selective effect on the gonadotroph secretory
      process, such that successive GnRH stimuli result in an increase in the maximal
      rate and mass of secretion of biologically active LH.

PMID- 1997521
TI  - Preliminary characterization of growth factors secreted by human pituitary
      tumors.
AB  - To investigate the secretion of mitogenic factors by human pituitary tumors we
      have cultured cells from 54 adenomas in serum-free medium. Conditioned media from
      28 (52%) elicited dose-dependent stimulation of [3H]thymidine incorporation into
      rat GH3 cells (22-338% above control), while 14 (26%) inhibited GH3
      proliferation. Stimulating activity was observed more frequently in nonfunctional
      tumor-conditioned medium (73%; n = 22) than in secretory tumor-conditioned medium
      (37%; n = 32). Of 10 tumour-conditioned media with mitogenic activity for GH3
      cells, only 4 produced modest stimulation of HEp2 (human laryngeal carcinoma)
      cells. In contrast, [3H]thymidine incorporation into A431 (human squamous
      carcinoma) and PC12 (rat adrenal pheochromocytoma) cells was enhanced by each of
      15 tumor-conditioned media (up to 342% and 275%, respectively), 8 of which had
      shown stimulatory and 2 inhibitory effects on GH3 cells. Gel filtration of pooled
      conditioned media from 10 nonfunctional tumors showed significant growth
      promoting activity for GH3 cells in fractions corresponding to mol wt of 2-3 and
      11-18 kDa. Proliferative activity on A431 cells also eluted in two positions; one
      corresponded to the higher mol wt peak seen with GH3 cells, while the other, not
      observed with GH3 cells, was in the 3- to 6-kDa range. These findings suggest
      that cells derived from human pituitary adenoma tissue synthesize and secrete
      several growth factors, each of which may have its own target cell specificities.
      These factors have yet to be characterized, but we suggest that they may have a
      role in stimulating the development or maintenance of human pituitary adenomas.

PMID- 1997522
TI  - Demonstration of the existence of the alternatively spliced form of thyroid
      peroxidase in normal thyroid.
AB  - We have investigated whether the alternatively spliced form of thyroid peroxidase
      (TPO), which has been shown clearly to occur in Graves' thyroid, is present in
      normal thyroid. We have performed a polymerase chain reaction on cDNAs prepared
      from normal thyroid mRNAs using primers 100 bases up-stream and down-stream from
      the 171 nucleotides that have been shown to be spliced out. Size analysis of the
      polymerase chain reaction products by agarose gel electrophoresis revealed bands
      at 0.2 and 0.37 kilobases (kb), sizes predicted to be obtained when the two forms
      of TPO cDNA are present. This was confirmed by hybridization with a 32P-labeled
      probe corresponding to the 20 nucleotides of the junction site. After stringent
      washing, the 0.2-kb band gave a clear positive signal, which was stronger than
      that of the 0.37-kb band despite the latter cDNA being more abundant. This
      demonstrates clearly that the alternatively spliced form of TPO exists in normal
      thyroid. Its significance is discussed.

PMID- 1997523
TI  - Calcium, vitamin D, and parathyroid hormone status in young white and black
      women: association with racial differences in bone mass.
AB  - The etiology of the racial disparity in bone mass and fracture rate is unknown.
      Since the PTH-vitamin D endocrine system is a major regulator of calcium
      metabolism and bone turnover, this cross-sectional study examined the
      relationship of radial and lumbar bone density to vitamin D metabolite and PTH
      concentrations and to calcium intake and excretion in 67 white and 70 black
      highly comparable, healthy, premenopausal women. Bone density at both radial and
      lumbar sites was higher in blacks than in whites. Serum 25-hydroxyvitamin D was
      slightly but not statistically significantly (P = 0.08), lower in blacks than in
      whites, but there were no racial differences in 1,25-dihydroxyvitamin D, PTH, or
      renal tubular maximum for reabsorption of phosphate. The mean 25-hydroxyvitamin D
      concentration in blacks was well within the normal range and was not associated
      with evidence of secondary hyperparathyroidism. There were no correlations of
      bone density to vitamin D or PTH concentrations. Although there were no racial
      differences in dietary intake of calcium and vitamin D or in sodium excretion, 24
      h urinary calcium excretion was significantly lower in blacks than in whites, and
      calcium excretion was inversely associated with radial bone density. In contrast
      to previous reports, in healthy, normal weight, premenopausal black women there
      is no evidence of vitamin D deficiency or secondary hyperparathyroidism,
      suggesting that factors other than the vitamin D-PTH axis are responsible for
      racial differences in bone mass.

PMID- 1997524
TI  - Altered patterns of pituitary secretion and renal excretion of free alpha-subunit
      during gonadotropin-releasing hormone agonist-induced pituitary desensitization.
AB  - Intact LH and free alpha-subunit (FAS) are differentially regulated during GnRH
      agonist (GnRHa)-induced pituitary desensitization; circulating levels of FAS
      rise, while LH levels decline. Increased steady state alpha and decreased LH beta
      mRNA levels in desensitized rat pituitaries suggest that differential regulation
      occurs at the level of subunit transcription. We assessed a renal contribution to
      these changes in serum hormone concentrations by studying LH and FAS levels in
      serum and urine in 15 pubertal children before and during long term GnRHa
      administration. Before GnRHa, serum LH and FAS were secreted in concordant
      pulses, and both responded briskly to exogenous GnRH. During GnRHa-induced
      pituitary desensitization, mean (+/- SEM) serum and urinary LH levels fell [11 +/
      3 vs. 2 +/- 0.2 IU/L (P less than 0.01) and 39 +/- 15 vs. 5 +/- 1 IU/g
      creatinine (P less than 0.05), respectively), and the LH response to exogenous
      GnRH was ablated (117 +/- 20 vs. 1 +/- 0.3 IU/L; P less than 0.01). In contrast,
      despite suppression of FAS pulsatility, mean serum FAS levels rose during GnRHa
      treatment (204 +/- 23 vs. 405 +/- 50 ng/L; P less than 0.01), and responsiveness
      to exogenous GnRH was maintained. Paradoxically, urinary FAS levels fell (3.2 +/-
      0.9 vs. 1.7 +/- 0.4 micrograms/g creatinine; P less than 0.05) as did its renal
      clearance (3.1 +/- 0.5 vs. 1.3 +/- 0.1 mL/min.m2; P less than 0.05). We conclude
      that during GnRHa-induced pituitary desensitization, the gonadotrope maintains
      the ability to respond to GnRH with FAS release, and the rise in serum FAS is due
      in part to its diminished renal clearance.

PMID- 1997525
TI  - Metabolic effects of growth factors and polycyclic aromatic hydrocarbons on
      cultured human placental cells of early and late gestation.
AB  - The metabolic effects of epidermal growth factor (EGF), insulin, insulin-like
      growth factor-I (IGF-I), and IGF-II were determined on human placental cells in
      monolayer culture obtained from early gestation (less than 20 weeks) and late
      gestation (38-42 weeks). Parameters studied were uptake of aminoisobutyric acid
      (AIB), uptake of 3-O-methylglucose and [3H]thymidine incorporation into cell
      protein. Since benzo[alpha]pyrene (BP) inhibits EGF binding and
      autophosphorylation in cultured human placental cells, particularly in early
      gestation, we also studied the effect of benzo[alpha]pyrene and other polycyclic
      aromatic hydrocarbons (PAHs) on EGF-mediated AIB uptake. The metabolic effects of
      EGF, insulin, and the IGFs in cultured human placental cells varied with
      gestational age and the growth factor studied. All three classes of growth
      factors stimulated AIB uptake in both early and late gestation at concentrations
      from 10-100 micrograms/L, well within a physiological range. However, insulin
      stimulation of AIB uptake was maximal at a high concentration (200 micrograms/L)
      in both early and late gestation cells, suggesting an action via type 1 IGF
      receptors rather than via insulin receptors. EGF stimulated 3-O-methylglucose
      uptake only in term placental cells. No significant stimulation of [3H]thymidine
      incorporation by any of the growth factors tested was seen with either early or
      late gestation cells. The effect of PAHs on AIB uptake by cultured placental
      cells was variable. BP alone stimulated AIB uptake by both very early and late
      gestation cells and enhanced EGF-stimulated AIB uptake. alpha-naphthoflavone
      alone inhibited AIB uptake at all gestational ages and inhibited EGF-stimulated
      AIB uptake. beta-Naphthoflavone and 3-methylcholanthrene minimally inhibited AIB
      uptake by early gestation cells and did not modify EGF-stimulated uptake at any
      gestational period. Our prior results demonstrated that BP more significantly
      inhibited EGF than IGF or insulin receptor binding as well as autophosphorylation
      in early gestation placenta, and that BP was the most potent of the PAHs tested.
      Thus, the direct effect of the PAHs on placental EGF receptors and amino acid
      transport may indicate altered function of EGF in the regulation of placental
      growth in smoking mothers that is developmentally regulated.

PMID- 1997526
TI  - Pneumocystis carinii infection of the thyroid in a hypothyroid patient with AIDS:
      diagnosis by fine needle aspiration biopsy.
AB  - A 49-yr-old homosexual man with acquired immunodeficiency syndrome presented with
      a left-sided neck mass. He was found to have a firm goiter. He was clinically
      euthyroid, but had laboratory evidence of primary hypothyroidism. Radioactive
      iodine scan of the thyroid showed homogeneous uptake over an enlarged right lobe
      and absence of uptake over the left lobe. Two fine needle aspiration biopsies of
      the thyroid revealed the presence of Pneumocystis carinii (P. carinii) organisms
      on the Gomori's methenamine silver strain. After courses of iv and oral therapy
      with trimethoprim-sulfamethoxazole, a third fine needle aspiration biopsy failed
      to reveal any organisms. A repeated radioactive iodine scan of the thyroid showed
      return of uptake over the left lobe. Thyroid function tests normalized with
      levothyroxine, and the goiter decreased in size. To our knowledge, this is the
      first report of hypothyroidism associated with P. carinii infection of the
      thyroid. P. carinii infection should be considered in the differential diagnosis
      of human immunodeficiency virus infected individuals presenting with cold thyroid
      nodules. Fine needle aspiration biopsy is a valuable tool in assessing these
      patients.

PMID- 1997527
TI  - The N-terminal sequence of the major erythropoietic factor of an anephric patient
      is identical to insulin-like growth factor I.
AB  - The erythropoietic factors present in an anephric patient with nearly normal
      hematocrit were isolated from plasma by reversed-phase and gel permeation HPLC.
      The most active fraction was purified and the analysis of its N-terminal sequence
      was identical to the published sequence of the human insulin-like growth factor I
      (IGF I). Recombinant human IGF I had identical elution positions as the isolated
      erythropoietic factor on reversed-phase HPLC and the same molecular weight on gel
      permeation HPLC. Furthermore, hrIGF I stimulated erythroid colony formation in
      human bone marrow cultures as was previously shown for the isolated human
      erythropoietic factor. These results suggest that IGF I may replace
      erythropoietin as a stimulator of erythropoiesis in some patients with anemia and
      renal failure.

PMID- 1997528
TI  - Current problems in microbiology: 1. Chlamydial infections: which laboratory
      test?

PMID- 1997529
TI  - Audit in histopathology: description of an internal quality assessment scheme
      with analysis of preliminary results.
AB  - In the first six months of a formal Internal Quality Assessment Scheme operating
      in the Department of Histopathology, Broadgreen Hospital, Liverpool, 1005 items
      of data were gathered, relating to 80 cases. The scheme entails a random 2%
      sample of biopsy specimens being selected, each case being analysed using a
      structured proforma, and a numerical scoring system being allocated to all
      aspects of specimen handling. Technical and secretarial performance was good
      while the quality of clinical information provided by the requesting clinician
      was poor. There was a wide variation in reporting times, which related partly to
      the complexity of the specimen, and partly to the degree of supervision required
      by the reporting pathologist. Month by month analysis of reporting times showed a
      significant increase in reporting times associated with rotation of junior staff,
      but not with periods of annual leave. Pathologist performance scores were good,
      but close examination of components of the overall score for an individual
      pathologist indicated occasional areas of weakness (such as the adequacy of the
      macroscopic report). It is concluded that this scheme is worthwhile and its
      practice will be continued indefinitely. The comprehensive nature of the analysis
      allows for the formal identification of areas of work which need improvement, and
      the allocation of a formal numerical score allows improvement in these areas to
      be monitored. The monthly meetings provide a means whereby performance scores are
      fed back to the participating pathologists, and they are also of general
      educational value regarding histological reporting practice. It is intended that
      the scheme be extended to include the assessment of special stains, frozen
      sections, and adequacy of the report delivery service. The system is easily
      adaptable for use within other histopathology departments.

PMID- 1997530
TI  - Continuous assessment of performance in External Quality Assessment Schemes.
AB  - A simple, standardised procedure was used for processing data from External
      Quality Assessment Schemes and for producing performance charts. A graphic
      presentation of cumulative performance is generated for each test, using an
      integrated software package to display results in a standardised format. This
      permits interpretation of satisfactory and poor performances and facilitates
      identification of "outlying" results. Although most results are recorded as
      Deviation Indices, the system is flexible and can be used to present other
      performance variables, such as Percentage Deviations and relevant textual
      information relating to interpretative assessments. It is therefore readily
      adaptable for use by other pathology disciplines.

PMID- 1997531
TI  - Evaluation of the pre-S (pre-S(1)Ag/pre-S(2)Ab) system in hepatitis B virus
      infection.
AB  - The diagnostic and prognostic value of pre-S(1)Ag and pre-S(2)Ab was investigated
      in 69 HBsAg surface antigen positive patients--14 with acute hepatitis B, 30 with
      chronic liver disease (six chronic persistent hepatitis, 14 chronic active
      hepatitis, 10 with cirrhosis) and in 25 asymptomatic carriers. Pre-S(1)Ag was
      found in all patients with chronic hepatitis B virus (HBV) infection regardless
      of viral replication. In contrast, pre-S(2)Ab was not detected in any patients.
      Acute hepatitis was studied sequentially with periodic controls at 20 day
      intervals. Pre-S(1)Ag cleared before HBsAg in six of 14 (43%) patients who
      progressed favourably, and the two antigens cleared simultaneously in eight of 14
      (57%) cases. Patients with early clearance of pre-S(1)Ag progressed favourably,
      thus indicating the prognostic value of this test, which, however, is still of
      limited practical application given the small temporal difference between the
      moment of clearance of the two antigens. The first markers to clear, however,
      were HBeAg and DNA-HBV, which showed significant differences with respect to the
      clearance of HBsAg. Moreover, pre-S(2)Ab appeared before HBsAb in 57.1% of our
      patients and was found in some patients before pre-S(1)Ag and HBsAg had cleared
      (42.8%), thus allowing complete viral clearance and acute HBV infection to be
      predicted earlier.

PMID- 1997532
TI  - Monocytoid B cell lymphoma.
AB  - The clinical, light microscopic, ultrastructural, immunocytochemical and
      cytogenetic features of a case of monocytoid B cell lymphoma were investigated.
      The tumour initially affected the cervical and supraclavicular nodes, but 33
      months later affected the left parotid salivary gland. The patient had
      subclinical Sjogren's syndrome. The neoplastic cells showed characteristic
      morphological features and had peri- and interfollicular distribution in the
      node. Immunocytochemically the tumour cells were L26, 4KB5, MB2, CD19, CD20, CD22
      and IgM/kappa positive. Prominent plasmablastic plasmacytoid differentiation was
      present in the recurrent tumour, suggesting an origin from post-follicular B
      cells. The lymphoma cells showed unusual cytogenetic abnormalities.

PMID- 1997533
TI  - Chromosomes in childhood acute lymphoblastic leukaemia: karyotypic patterns in
      disease subtypes.
AB  - To define further the clinical importance of cytogenetic analysis in acute
      lymphoblastic leukaemia (ALL) a prospective study was performed on 139 unselected
      children. Analyses were considered adequate in 104, of whom 35 were normal and 69
      had clonal abnormalities. Abnormalities were categorised according to banded
      chromosome analysis as well as chromosome count. Karyotypes were correlated with
      clinical and laboratory features at diagnosis and with survival. Of the
      successful analyses, thirty five (34%) children had no abnormalities; this group
      contained an excess of T cell disease. Twenty five (24%) had a "characteristic"
      hyperdiploid karyotype and as a group had lower presenting white counts, a
      tendency to CD10, and periodic acid schiff positivity of the blast cells and
      smaller spleens. None was an infant and only one was over 10 years old. Seven
      (7%) children with t(9; 22), t(8; 14), or t(4; 11) translocations were grouped
      together as "specific" translocations. Collectively they had a significantly
      worse prognosis than the remainder. Nine children developed central nervous
      system relapse, six of whom had either t(4; 11) or abnormalities of 9p or 19p. A
      descriptive classification taking into account chromosome bonding pattern is
      cytogenetically more appropriate and may be more clinically useful than grouping
      children simply by chromosome number. As knowledge and techniques improve, the
      classification of cytogenetic abnormalities in ALL will need to be kept under
      frequent review.

PMID- 1997534
TI  - Breakdown of gastric mucus in presence of Helicobacter pylori.
AB  - The potential of Helicobacter pylori to degrade gastric mucus was examined.
      Colonies of H pylori cultured from antral mucosal biopsy specimens of patients
      with non-autoimmune gastritis were washed with sterile saline, passed through a
      sterilisation filter, and the filtrate examined for urease, protease, and
      mucolytic activity. The filtrate failed to hydrolyse bovine serum albumin, or to
      degrade stable mucus glycoprotein structures of high particle weight that had
      been separated from human gastric mucus on Sepharose 2B. The high particle weight
      mucus glycoprotein was, however, extensively degraded when incubated with H
      pylori filtrate (which possessed urease activity) in the presence of 2 M urea, to
      release fragments of Mr approximately 2 X 10(6). The high particle weight mucus
      glycoprotein was also broken down to a comparable extent when incubated with Jack
      bean urease in the presence of 2 M urea, or 1 M ammonium carbonate, or 40 mM
      carbonate-bicarbonate buffer (pH 8.7), but not when treated with 4 M urea alone,
      or Jack bean urease alone. These results indicate that the loss of high particle
      weight mucus glycoprotein in gastric mucus from patients with gastritis and
      gastric ulcers is unlikely to be due to the mucolytic action of an extra-cellular
      protease produced by H pylori, but it may result from the destabilising effects
      of a carbonate-bicarbonate buffer, generated at the mucosal surface when H pylori
      urease hydrolyses transuded plasma urea.

PMID- 1997535
TI  - Survey of users' attitudes to their local microbiology laboratory.

PMID- 1997536
TI  - Measurement of urinary lipopolysaccharide antibodies by ELISA as a screen for
      urinary tract infection.
AB  - Five hundred and twenty two clinical urine specimens submitted for routine
      microbiological examination were tested in parallel by conventional microscopy
      and culture and for lipopolysaccharide antibodies by an enzyme linked
      immunoabsorbent assay (ELISA) to assess the ELISA as a screen for urinary tract
      infection. When the ELISA alone was compared with routine methods the specificity
      sensitivity, and predictive value of positive and negative tests was 73.2%,
      75.7%, 51.1% and 38.5%. For ELISA with microscopy the same variables were 71.1%,
      82.2%, and 92.4% and 94.7%, respectively. The ELISA absorbency increased with
      increasing bacterial numbers, but results varied widely. Only 65.4% of urines
      which contained greater than or equal to 10(5) bacteria/ml were positive by
      ELISA; 36.8% of urines with less than 10(3) bacteria/ml were positive by ELISA;
      100% of greater than or equal to 10(5) bacteria/ml cultures of Pseudomonas sp (n
      = 4), Staphylococcus aureus (n = 3), and Streptococcus faecalis (n = 2) were
      positive by ELISA but only 71.4% of Proteus sp (n = 7), 61.4% coliforms (n = 70),
      and 25% of coagulase negative staphylococci (n = 4). It is concluded that further
      development is required before the ELISA can be used for routine screening for
      urinary tract infection.

PMID- 1997537
TI  - Increased serum beta 2-microglobulin concentrations in hyperthyroid states.
AB  - Serum beta 2-microglobulin concentrations were determined in 21 untreated
      hyperthyroid patients (12 with Graves' disease, and nine with toxic nodular
      adenoma) and in 20 healthy controls. All subjects had normal serum creatinine
      concentrations and urine analysis. Both total and free thyroid hormones were
      significantly higher in the hyperthyroid groups than in controls. Beta 2
      microglobulin concentrations were significantly increased in both groups of
      hyperthyroid patients compared with controls. No difference was found in the
      thyroid hormone and beta 2-microglobulin concentrations between both sets of
      patients. The beta 2-microglobulin and thyroid hormone concentrations were not
      correlated. These data show that hyperthyroidism is another cause of increased
      beta 2-microglobulin production along with viral infections, immunologically
      mediated diseases, and malignant neoplasms. The increased serum beta 2
      microglobulin concentration in thyroid hyperfunction is probably related to
      metabolic rate, even if autoimmunity might contribute to its overproduction.

PMID- 1997538
TI  - Detection of chloramphenicol resistance in Haemophilus influenzae.
AB  - An average of 358 (13%) of United Kingdom laboratories failed to detect
      resistance to chloramphenicol in strains of Haemophilus influenzae distributed by
      the United Kingdom National External Quality Assessment Scheme for Microbiology.
      Clear associations between methods used and results obtained show that error
      rates are minimised by the use of low content (10 micrograms) disc and a
      sensitive control strain of H influenzae.

PMID- 1997539
TI  - Retrospective application of prognostic indices to pancreatitis discovered at
      necropsy.
AB  - Six prognostic indices, which were developed to assess inpatients with acute
      pancreatitis, were evaluated for possible retrospective application. When applied
      to a series of 14 cases in whom pancreatitis was first diagnosed at necropsy, the
      index devised by Jacobs et al was found to be the most useful, because in nine of
      these cases eight or more of the variables required were available for assessment
      from the case records. In the other indices evaluated fewer than eight of the
      required variables were available for retrospective assessment in most cases.
      Although undiagnosed pancreatitis is probably uncommon as a sole cause of death,
      the retrospective use of one or more of these indices may help assess the
      severity of the patient's condition on admission to hospital.

PMID- 1997540
TI  - HLA antigens in Hungarian patients with idiopathic haemochromatosis.
AB  - Thirteen unrelated patients with idiopathic haemochromatosis (eight men, five
      women) were studied. The diagnosis was based on clinical, biological, and
      histochemical findings. HLA typing was performed in all 13 and in all of their
      available first degree relatives (n = 31). HLA A3 was present in nine of 13
      probands (69.2% compared with 18.8% in the group of 53 healthy blood donors and
      22.4% in a selected Hungarian population (n = 1910). HLA B7 was present in five
      of 13 probands (38.4% compared with 11.3% and 14.6%). An A3B7 antigen association
      was found in five of 13 patients. The A3B7 haplotype was found in three, A2B12
      and A2B38 haplotypes were found twice in 10 genotyped probands. Pedigree studies
      showed that there was one unaffected homozygote, 24 heterozygotes, and six non
      carriers. Extended family and population studies are necessary to establish the
      prevalence of the gene in Hungary and an association with haplotypes other than
      A3B7.

PMID- 1997541
TI  - Cytogenetic analysis of a granulocytic sarcoma in a patient without systemic
      leukaemia.
AB  - Granulocytic sarcoma is a rare complication of leukaemia. Occasionally it
      presents before the development of systemic leukaemia when diagnosis may be
      difficult. A case of granulocytic sarcoma occurring in a patient with no overt
      evidence of leukaemia, but in whom cytogenetic analysis of the bone marrow showed
      a clonal t(12;13) translocation, is reported. Cytogenetic analysis of tissues in
      this disease may indicate evidence of systemic disease before overt morphological
      changes.

PMID- 1997542
TI  - Comparison of two commercial kits for identifying and biotyping Haemophilus
      parainfluenzae.
AB  - The Minitek system and the more recently introduced Micro Scan HNID panels for
      the identification and biotyping of 98 V dependent Haemophilus isolates were
      compared. Identical results were obtained for 77 isolates. The discrepancy in the
      results of ornithine and urease was accounted for mainly by the mismatching of
      the identification by the two kits. When 13 isolates of H parainfluenzae with
      mismatched biotypes were re-examined, the results from Micro Scan correlated with
      92% of those obtained by Christensen's urea broth and 100% by the ornithine test
      (Lab M); the corresponding figures for Minitek were 61% and 30%, respectively.
      Micro Scan was easy to handle on the bench and results were ready on the same
      day. These results suggest that further work is required to assess these two
      systems for the biotyping of H parainfluenzae.

PMID- 1997543
TI  - Examination of faeces for bacterial pathogens.

PMID- 1997544
TI  - Guidelines on oral anticoagulation: second edition.

PMID- 1997545
TI  - Hypercalcaemia in lymphoma.

PMID- 1997546
TI  - Differential marking of surgical excision planes.

PMID- 1997547
TI  - Prognostic index for breast carcinoma: a 22% improvement in the prediction of
      outcome?

PMID- 1997548
TI  - Correction in dietary guidelines article.

PMID- 1997549
TI  - Food packages for the WIC Program.

PMID- 1997550
TI  - Nutrition isn't color blind.

PMID- 1997551
TI  - The relationship of loneliness, social isolation, and physical health to dietary
      adequacy of independently living elderly.
AB  - This study evaluated the dietary adequacy of elderly individuals to determine
      whether factors such as loneliness, social isolation, or physical health were
      related to nutrient intake. The participants (n = 61) were independently living
      individuals aged 60 to 94 years recruited through senior citizen centers,
      residential housing areas, and social agencies in Rutherford County, Tennessee.
      Three-day food records were used to collect dietary data, and nutrient intakes
      were compared with the 1989 Recommended Dietary Allowances. Three-day social
      contact diaries were used to measure frequency of interaction with others. The
      Physical Health Questionnaire was used to evaluate subjectively the number and
      severity of disease states, and the loneliness index was computed using the
      revised UCLA Loneliness Scale. Energy and calcium were most likely to be
      underconsumed, and poor physical health was related to decreased intakes of
      vitamin A and ascorbic acid. Loneliness was related to dietary inadequacies. We
      recommend emphasis on education and services to provide home-delivered meals and
      groceries as well as affordable convenience foods of high nutrient density to
      enable older individuals to achieve adequate nutrient intake while maintaining an
      independent life-style.

PMID- 1997552
TI  - Inpatient and post-discharge course of the malnourished patient.
AB  - A retrospective review of the medical records of 114 malnourished and 106 non
      malnourished male veterans assessed the inpatient and 1 year post-discharge
      dietetic care given for the treatment of malnutrition. The malnourished sample
      consisted of subjects discharged with a protein-energy or protein malnutrition
      comorbidity. Subjects in the diagnosis-matched and age-matched control sample
      were discharged without a malnutrition comorbidity during the same period. Data
      collected from progress notes included diagnoses, inpatient dietetic feedings and
      services provided, discharge dietetic care, intervening clinic visits, and
      rehospitalizations. On initial admission, 79% of the diagnoses for the
      malnourished group fell into five diagnosis categories: neoplasms; respiratory
      system diseases; digestive system diseases; endocrine, nutritional, and metabolic
      diseases; and mental disorders (including alcohol-related disorders).
      Malnourished subjects received more specialized feedings and dietetic services
      than did the controls on initial admission. However, the discharge and post
      discharge care received by surviving members of both groups was similar. Fewer
      than half the members of either group received post-discharge care. Fifty-four
      malnourished and 54 control patients were hospitalized more than once. The
      findings indicate that levels of inpatient and outpatient dietetic care need to
      be coordinated to alleviate malnutrition.

PMID- 1997553
TI  - Acceptance of quantity recipes with zero added salt by a military population.
AB  - The average civilian young man consumes approximately 5.5 g sodium daily in food
      plus an additional 20% as added salt. The average intake of military personnel
      may exceed this civilian level. The Surgeons General of the Military Services
      established 1,700 mg sodium per 1,000 kcal as the goal for sodium content in
      menus served in military dining facilities. We tested the acceptability of
      quantity recipes with zero added salt and control recipes with added salt in
      military dining facilities. Twenty-eight test recipes with zero added salt were
      prepared and offered on the regular serving line. Military personnel selecting
      the test items rated them for acceptability on a nine-point hedonic scale. Only 6
      of the 28 recipes with zero added salt were rated significantly less acceptable
      than the control recipes. Chemical analysis of the test recipes showed an 11% to
      87% reduction in sodium and a 28% to 80% reduction in chloride. Our results
      indicate that dietitians and/or foodservice managers can produce quantity food
      recipes that are reduced in sodium and acceptable to customers.

PMID- 1997554
TI  - Comparison of a food frequency questionnaire using reported vs standard portion
      sizes for classifying individuals according to nutrient intake.
AB  - Individual intakes of retinol, carotene, vitamin C, and folacin calculated from a
      food frequency questionnaire using reported portion size were compared with
      intakes calculated using standard portion size information. Data from a case
      control study to determine the association of nutrient intake and risk of
      cervical dysplasia were supplemented by standard portion size information from
      the US Department of Agriculture and reanalyzed. Significant mean differences
      were found between intake calculated from reported portion size data and that
      calculated from standard portion size data for all nutrients. Correlation of
      nutrient intakes obtained by the two methods of data collection ranged from .73
      to .92. Calculation of the rho statistic, measuring the consistency of
      classification of participants into groups of high, medium, and low nutrient
      intake, led to values ranging from .55 to .71, indicating some misclassification
      of study participants. To determine the effect misclassification had on the study
      outcome, odds ratios were calculated using nutrient amounts obtained from both
      methods of collecting portion size data. Results indicate that replacing reported
      portion size data with standard portion size data may lead to conflicting
      outcomes for specific nutrients in research concerning the relationship between
      diet and disease.

PMID- 1997555
TI  - Nutrition training, attitudes, knowledge, recommendations, responsibility, and
      resource utilization of high school coaches and trainers.
AB  - Because misconceptions about nutrition are prevalent in athletics, we assessed
      the knowledge of sports-related nutrition concepts of high school athletic
      personnel. A questionnaire was mailed to all athletic directors and teacher
      athletic trainers in North Carolina high schools. Of the 821 surveys sent, 303
      were returned (a response rate of 37%). The sample was grouped into three
      categories on the basis of the perceived role of the respondent: coach (n = 152),
      trainer (n = 91), and dual coach-trainer (n = 29). Thirty-one individuals who
      indicated that they held administrative positions with little or no contact with
      students were omitted from the analysis. One-way analysis of variance or chi 2
      was used to examine differences in questionnaire responses among the three
      groups. In comparison with high school coaches, trainers had taken more workshops
      or courses related to nutrition (2.9 compared with 1.8) and had more frequently
      used professional meetings (62% vs 39%), workshops (64% vs 41%), and textbooks
      (75% vs 50%) as sources of information. Trainers were more knowledgeable about
      nutrition (9.6 correct responses vs 8.9 for coaches) and recommended desirable
      nutrition practices more often than coaches (7 of 9 vs 6 of 9). There was some
      disagreement between coaches and trainers in their perceptions of who was more
      important in dispensing nutrition information. Future nutrition education efforts
      should take into account the differences among these groups.

PMID- 1997556
TI  - An eating plan and update on recommended dietary practices for the endurance
      athlete.
AB  - This article presents a six-group exchange food plan for the endurance athlete.
      The plan allows approximately 1,850, 3,460, and 3,760 kcal for a weight reduction
      diet, general training diet, and carbohydrate-loading intake plan, respectively.
      Because complex carbohydrate is the primary source of fuel, the training diet and
      the carbohydrate-loading diet contain 500 g and 600 g carbohydrate, respectively,
      whereas in the weight reduction plan more than 60% of total energy is
      carbohydrate. Overall nutrient adequacy of the exchanges and fluid needs for the
      athlete are discussed. Recommendations and protocol for current dietary practices
      are given. Dietitians are encouraged to assess the caloric needs of their clients
      and to individualize the suggested plans in accordance with the needs of each
      athlete.

PMID- 1997557
TI  - Selected traditional and contemporary foods currently used by the Pima Indians.

PMID- 1997558
TI  - Milk and milk products in low-residue diets: current hospital practices do not
      match dietitians' beliefs.

PMID- 1997559
TI  - Variation in nutrient intake of college students: a comparison by students'
      residence.

PMID- 1997560
TI  - Dietary change in participants of the Better Eating for Better Health course.

PMID- 1997561
TI  - The use of voice mail in a nutrition and cancer information telephone service.

PMID- 1997562
TI  - A comparative study of bimetal and digital thermometers.

PMID- 1997563
TI  - Mammalian aging, metabolism, and ecology: evidence from the bats and marsupials.
AB  - This study compared trends in body size, life span, metabolic rate, and ecology
      of bats and marsupials with those from mammals generally, using a 580 species
      data base. The linear logarithmic relationship between mammalian body mass and
      maximum longevity, deleting bats and marsupials, is used as a standard against
      which to measure life spans of particular mammal groups. Bats have maximum life
      spans a minimum of 3 times those of nonflying eutherians--a trend resulting from
      neither low basal metabolic rate, the ability to enter torpor, nor large relative
      brain size. Marsupials live about 80% as long as nonflying eutherians despite
      averaging lower basal metabolic rates; similarly, there is no effect of
      heterothermy or relative brain size. These results directly conflict with
      predictions of both "rate of living" and brain-size mediated theories of aging.
      However, they are consistent with an evolutionary theory that posits
      exceptionally long life spans among mammals with reduced environmental
      vulnerability.

PMID- 1997564
TI  - Relation of age and physical exercise status on metabolic rate in younger and
      older healthy men.
AB  - We examined the influence of age and habitual physical exercise level on resting
      metabolic rate (RMR) and thermic effect of a meal test (TEM) by studying
      sedentary and physically active younger and older men. RMR was measured using a
      ventilated hood and TEM for 180 min after ingestion of a liquid meal. RMR,
      adjusted for fat-free weight (FFW) and percent body fat, was lower in sedentary
      older men relative to the other three groups. TEM (kcal.180 min-1) was highest in
      active younger (77.3 +/- 3.7) and active older men (69.8 +/- 7.0) relative to
      sedentary younger (53.1 +/- 4.0) and sedentary older men (51.5 +/- 6.9). TEM was
      not related to age or body composition. A sedentary life style in older men may
      be associated with a lower RMR, independent of FFW and percent body fat, relative
      to younger men and older men who regularly exercise. Participation in physical
      exercise, regardless of age, is associated with a higher TEM.

PMID- 1997565
TI  - Gradual delay in glucose-induced first phase insulin secretion by the pancreatic
      islets of 7 week-, 6 month-, and 1 year-old rats.
AB  - The temporal profiles of insulin secretion by isolated pancreatic islets of male
      Wistar rats with various ages up to 1-year-old were studied using high glucose,
      potassium (K+) depolarization, and arginine as secretagogues. In the islets of 6
      month-old rats, the onset and peak of glucose-induced first phase of insulin
      release were delayed for 1 min compared to those of 7--week-old rats. The onset
      and peak were further delayed for 1 min in the islets of 1-year-old rats. The
      onset of glucose-induced second phase of insulin secretion, and the onset and
      peak of K+ depolarization- and arginine-induced insulin release were not delayed
      in the islets of 6-month and 1-year-old rats. Glucose-stimulated increase in
      cytosolic free calcium ([Ca2+]i) seemed not delayed in the islets of 1-year-old
      rats. We conclude that the first phase of glucose-induced insulin release by the
      islets is selectively delayed as rat ages. It was suggested that the defect lies
      distal to the elevation of [Ca2+]i.

PMID- 1997566
TI  - Strain differences in baroreflex inhibition by centrally infused enalapril in old
      rats.
AB  - To determine whether inhibition of the brain renin-angiotensin system would
      affect baroreflexes similarly in old rats of different strains, we compared 24
      month-old male Fischer 344 and Sprague-Dawley rats. Baroreflex sensitivity was
      tested while the rats were awake by recording reflex heart rate responses
      elicited as blood pressure was elevated with phenylephrine or lowered with sodium
      nitroprusside. Sprague-Dawley rats had higher blood pressures and lower heart
      rates initially. Chronic infusion of enalapril, a converting enzyme inhibitor,
      into a lateral cerebral ventricle (ICV) for two weeks lowered blood pressure in
      Sprague-Dawley but not in Fischer 344 rats. Furthermore, reflex bradycardia was
      unaffected in either rat strain, but reflex tachycardia was selectively
      suppressed in Fischer 344 rats. Thus, although time controls were not done to
      rule out spontaneous changes during the 14-day infusion period, these results
      suggest that central cardiovascular regulation does not change similarly with age
      in these two rat strains. As removal of the brain renin-angiotensin system
      lowered blood pressure in one strain and inhibited reflex tachycardia in the
      other, the divergence could mean that the brain renin-angiotensin system acts
      differently to keep blood pressure elevated in Sprague-Dawley rats and modulate
      reflex tachycardia in Fischer 344 rats.

PMID- 1997567
TI  - Effect of aging on GHRF-induced growth hormone release from anterior pituitary
      cells in primary culture.
AB  - Five criteria were developed to validate the primary cell culture model for
      comparison of GRF-induced release of growth hormone in pituitary tissue from
      aging animals. Pituitaries from young (5-mo), middle-aged (14-mo), and old (24
      mo) male Fischer 344 rats were dispersed using either trypsin/trypsin inhibitor
      or dispase and compared with respect to the number of pituitary cells recovered,
      cell viability, 3H-leucine incorporation into total protein, time course for
      recovery of optimal response to GRF, and the dose-relationship for GRF-induced
      release of growth hormone 2, 4, and 6 days after dispersal. Results indicated
      that direct comparison of cellular responses between tissues from young, middle
      aged, and old rats in primary cell culture is confounded by variations in time
      for recovery of optimal responses, the effects of the enzymes used for dispersal,
      and the methods used to express the data.

PMID- 1997568
TI  - Lack of effect of age and dietary restriction on DNA single-stranded breaks in
      brain, liver, and kidney of (C3H x C57BL/10)F1 mice.
AB  - Single-stranded DNA breaks in brain, liver, and kidney of (C3H x C57BL/10)F1 mice
      6 and 25 months of age on two dietary regimens (isonutrient diets at 85 and 50
      kcal/week) were investigated by means of fluorometric analysis of DNA unwinding
      in alkaline solutions. No age-dependent alterations were found for either control
      or dietary restricted groups. Except for possible differences for liver in the
      young age groups, there were no significant differences in the amount of single
      stranded DNA breaks between control and dietary restricted mice. These results
      suggest that the antiaging effects of dietary restriction in rodents are not
      mediated by a change in the number of accumulated nuclear DNA stranded breaks in
      internal organs.

PMID- 1997569
TI  - Histone H2A variant synthesis in aging human diploid cells.
AB  - The synthesis of the various classes of core particle histones was determined in
      human diploid fibroblast-like cells of different in vitro ages as they were
      stimulated to enter the cell cycle. Histone H2A synthesis in older populations
      was lower during G1 but was similar to younger cells at G0/G1 and S phases. The
      reduced synthesis during G1 was primarily the result of a decline in the
      synthesis of the H2A.1/.2 component.

PMID- 1997570
TI  - Quality of life in elderly, chronically ill outpatients.
AB  - Quality of life (QL) in elderly outpatients is poorly characterized. We
      interviewed 258 elderly outpatients from three health care settings to identify
      the attributes and events that affect self-assessment of QL. These outpatients
      rated their QL as acceptable, citing medical care, health, interpersonal
      relationships, financial status, and functional status as affecting their QL.
      Overall QL ratings were not strongly associated with objective indicators such as
      demographic characteristics and use of health care services. Subjective
      indicators, including patient perceptions of health, memory, and financial
      concerns, were correlated independently with global QL (sigma R2 = .35). We
      conclude that older, chronically ill patients generally consider their QL to be
      acceptable and affected by a variety of factors, including their perceptions of
      their emotional, socioeconomic, intellectual, and physical functioning.
      Furthermore, QL is poorly associated with objective indicators. Thus, in
      assessing the QL of elderly, chronically ill outpatients, physicians should
      elicit information regarding these perceptions.

PMID- 1997571
TI  - Electroencephalographic sleep in the healthy "old old": a comparison with the
      "young old" in visually scored and automated measures.
AB  - This report extends the normative study of sleep into healthy 80-year-olds and
      compares them with healthy 70- and 60-year-olds. We observed stability of sleep
      efficiency and rapid eye movement sleep across three decades of late life, but a
      slight decline of slow-wave sleep in the 80-year-olds (decreased total delta wave
      counts). Women showed better preservation of slow-wave sleep than men. Automated
      EEG period analysis of this phenomenon demonstrated higher rates of delta wave
      production in the first NREM sleep period of women compared to that of men, a
      finding associated with longer REM sleep latencies in women. Unexpectedly, 80
      year-old women showed decay in sleep maintenance, while 80-year-old men
      demonstrated stability of sleep maintenance, relative to their respective 60- and
      70-year-old counterparts. Implications for the understanding of sleep and its
      regulation in health and aging are discussed.

PMID- 1997572
TI  - Reliability of isometric hip abductor torques during examiner- and belt-resisted
      tests.
AB  - The purposes of this study were to determine the test-retest reliability of
      isometric hip abductor torques in elderly females, to compare two assessment
      protocols, and to compare the performances of elderly and young females. Twenty
      elderly and 20 young women were tested on two occasions. During the examiner
      resisted test the examiner provided the resistance, and during the belt-resisted
      test the subject's contralateral leg provided the resistance while the examiner
      positioned the dynamometer. A four-way ANOVA indicated no occasion effects (p
      greater than .05). Within each group, similar torques were produced by both legs
      (p greater than .05). Test-retest intraclass reliability coefficients were good
      to-high, ranging from 0.84 to 0.98 for the eight combinations of group-method
      leg. The elderly females produced 61% of the torques produced by young females (p
      less than .01), and the examiner-resisted method produced 65% of the torques
      produced using the belt-resisted method (p less than .01). The belt-resisted
      method required less physical effort on the part of the tester, provided greater
      stabilization of the pelvis, and was preferred by 95% of the subjects.

PMID- 1997573
TI  - Value of combined assessment of physical health and functional status in
      community-dwelling aged: a prospective study in Florence, Italy.
AB  - A survey of the health and social conditions of a representative sample of 967
      persons aged 60 years and older from the city of Florence, Italy, was undertaken
      in 1980. In 1987, a follow-up survey of this cohort was performed. There were 391
      documented deaths, 408 survivors, and 168 individuals who could not be located.
      Functional ability at baseline was assessed using a World Health Organization 14
      item scale. Indicators of physical health status included chronic disease status,
      number of drugs, physician visits, and days of hospitalization. After adjustment
      for age and sex, both functional ability and indicators of physical health status
      were found to be independent, statistically significant predictors of mortality.
      The results of this study further support the view that biomedical and functional
      assessment are both necessary for a comprehensive evaluation of the older
      population.

PMID- 1997574
TI  - Relationship of obesity and physical fitness to cardiopulmonary and metabolic
      function in healthy older men.
AB  - The relationship of obesity and physical fitness (VO2max) to cardiopulmonary and
      metabolic function was examined in 132 healthy obese, nonsmoking men age 45-79.
      Obese men with higher VO2max had lower % body fat and waist-to-hip ratio (WHR)
      than obese men with low VO2max. The obese subjects with high WHR (upper body fat
      distribution) had higher systolic blood pressure, hyperinsulinemia and impaired
      glucose tolerance, lower high density lipoprotein cholesterol (HDL-C), and higher
      triglyceride (TG). VO2max (ml/kg FFM.min) was lower in the older men (r = -0.54,
      p less than .001), and 32% of the variation was accounted for by age and the one
      second forced expiratory volume. Although pulmonary function was normal, 50% of
      the variability was predicted by age, height, and VO2max or WHR. Glucose
      tolerance and insulin correlated better with VO2max and indices of body
      composition than with age, while plasma TG and HDL-C correlated with body
      composition, not VO2max or age. Thus, while age affects the cardiopulmonary and
      metabolic function of obese older men, physical inactivity, obesity, and an
      abdominal body fat distribution (increased WHR) contributed significantly to
      their reductions in physiological function.

PMID- 1997575
TI  - An adult development study of contextual memory.
AB  - This study tested the hypothesis that there is a relatively greater decrease in
      memory for contextual features than in memory for target information with
      increasing age. Young, middle-aged, and elderly adults were presented with a
      number of slides, each of which contained a word centered on a background
      composed of either a landscape/cityscape or a border design. One third of the
      subjects were told to remember the words, one third were told to remember the
      backgrounds, and one third were told to remember the word-and-background pairs.
      Recognition memory for both words, backgrounds, and word-and-background pairings
      was tested in all subjects. The interaction between age, instruction condition,
      and type of information tested was not significant. Thus, there was no support
      for the hypothesis that older adults have a greater deficit in contextual memory
      than in memory for target information when compared to younger adults.

PMID- 1997576
TI  - The role of pain in the last year of life of older persons.
AB  - A random sample of 200 decreased older community residents was studied with a
      focus on the role of pain in the last year of life. Interviews with a surviving
      close person elicited retrospective reports. Pain increased over the final year;
      one month before death 66% felt pain frequently or all of the time, substantially
      higher than a matched comparison group of living persons (24%). For both groups
      across the year, pain was associated with most measures of behavioral competence,
      perceived quality of life, and psychological well-being. Hierarchical multiple
      regressions indicated that background and health variables explained 28% to 32%
      of the variance of pain over the year. Controlling for background variables and
      health, pain contributed significantly to lowered happiness and to depression,
      but had no independent impact on hope and interest in the world. After
      controlling for physical health, the older old were judged to have less pain than
      the younger old.

PMID- 1997577
TI  - Structured assessment of independent living skills: preliminary report of a
      performance measure of functional abilities in dementia.
AB  - Assessment of functional abilities is integral to the diagnosis and management of
      elderly patients with dementia. We present a measure of activities of daily
      living, the Structured Assessment of Independent Living Skills (SAILS), and
      report preliminary reliability and validity data for 18 patients with Alzheimer's
      disease (AD) and 18 age- and education-equivalent controls. The SAILS utilizes
      behaviorally anchored rating scales to directly assess 10 areas of everyday
      functioning: Fine Motor Skills, Gross Motor Skills, Dressing, Eating, Expressive
      Language, Receptive Language, Time and Orientation, Money-Related Skills,
      Instrumental Activities, and Social Interaction. AD patients scored significantly
      worse than controls in all 10 areas. High correlations were obtained between the
      SAILS, visuospatial abilities, attention, and visual memory. In contrast, verbal
      memory, degree of depression, and praxis were not significantly correlated with
      the SAILS. The SAILS offers a criterion-based means of quantifying patient
      functional status for both clinical and research applications.

PMID- 1997578
TI  - Decision criteria for pure-tone detection used by two age groups of normal
      hearing and hearing-impaired listeners.
AB  - Response criteria from a yes-no task and detection thresholds from two test
      procedures were measured for four groups of adults: younger normal-hearing, older
      normal-hearing, younger hearing-impaired, and older hearing-impaired. The two
      test procedures were an audiological procedure (which does not control for
      response bias) and a 21FC adaptive procedure (which does control for bias). The
      signal was a 500 or 4000 Hz tone presented in quiet. All four groups showed an
      equally conservative response bias in the yes-no task. In addition, neither age
      nor hearing loss affected the difference (6.5 dB) between the two threshold
      measures.

PMID- 1997579
TI  - The effects of rate, sequencing, and memory on auditory processing in the
      elderly.
AB  - Auditory sequencing, rate, and memory were evaluated in three age groups with a
      series of subtests that require the identification of tones (Repetition Test;
      Tallal & Piercy, 1973). The older elderly group (M age = 80), but not the younger
      elderly group (M age = 70), performed significantly (p less than .05) poorer than
      the young adult group (M age = 25) when auditory memory of 4 and 5 tones was
      required and when the interstimulus interval was decreased. Performance was not
      related to hearing sensitivity, thus suggesting that changes in the auditory
      mechanism that occur with age may encompass more than a loss of hearing
      sensitivity. Moreover, performance on the Repetition Test did correlate with
      memory for digits, which indicates a relationship between auditory processing and
      higher cortical functions.

PMID- 1997580
TI  - Cross-sectional age differences and longitudinal change on the Bradburn Affect
      Balance Scale.
AB  - Cross-sectional age differences and longitudinal change were examined on
      psychological well-being, positive affect, and negative affect, as measured by
      the Bradburn Affect Balance Scale. Data were collected from 1,159 participants in
      1971 and 1985. Cross-sectional analyses showed age differences: older cohorts
      reported greater overall well-being but lower levels of both positive and
      negative affect when compared to younger respondents. Longitudinal analyses
      indicated small but significant changes toward decreased positive and negative
      affect but increased overall well-being. Negative affect had the strongest effect
      size. Positive and negative affect showed different patterns of change for
      different age groups. Taken together, cross-sectional and longitudinal findings
      suggest that change in affect variables is age-related, although these changes
      are relatively small. More evident was a pattern of correlational stability with
      age. Finally, the pattern of the results supports a two-factor theory of
      psychological well-being.

PMID- 1997581
TI  - On the generalizability of the age-related decline in coping with high-arousal
      conditions in a precision sport: replication and extension.
AB  - Two field experiments are reported in which highly skilled miniature golf players
      varying in age were examined during training and competition (Swedish
      championships). Number of shots, heart rate, and subjective ratings of anxiety
      were registered. Results indicated that young and older adult players exhibited a
      similar increase of competitive anxiety from training to competition, as
      evidenced by both measures of arousal. In addition, whereas older players
      deteriorated in motor performance during competitive play, young players improved
      motor performance in competition. This pattern of results replicates and extends
      previous research. It is suggested that the data reflect age-related differences
      in the ability to cope with high-arousal conditions as a result of age-related
      deficits in task-relevant cognitive abilities.

PMID- 1997582
TI  - Nonorganizational religious participation among elderly black adults.
AB  - This study investigated rates of participation in nonorganizational religious
      activities of elderly Black adults. Four indicators of participation were
      examined: reading religious materials, watching or listening to religious
      programs, prayer, and requests for prayer. Demographic, religious denomination,
      and health disability factors influenced participation in these behaviors. The
      findings were discussed for their implications for the development of a
      multidimensional conceptualization of religiosity.

PMID- 1997584
TI  - Population aging patterns: the expansion of mortality.
AB  - We used the hypothesis of mortality compression as a framework to examine
      patterns of mortality from 1962 to 1984. Data from national vital statistics
      records were used for analysis of the changing age at death for percentiles of
      the population. Data from the Social Security Administration and the U.S. Census
      Bureau were used to calculate the force of mortality. The mean age at death for
      all percentiles, including the oldest groups, has risen during the interval.
      Examination of the coefficient of variation for the mean age at death suggests
      that there is a relative increase in the variability of age at death among the
      oldest old. The available data do not fit a hypothetical sequence of normal
      density distributions with an increasing mean and declining standard deviation.
      The force of mortality in those over 85 years appears to be decreasing in a
      pattern similar to that for those under 85 years. Current mortality patterns
      suggest an "expansion," rather than compression, of mortality at the oldest ages.
      Further refinement of these observations, with improved data on mortality among
      the oldest old, will be helpful in delineating mortality patterns.

PMID- 1997583
TI  - Health perceptions and survival: do global evaluations of health status really
      predict mortality?
AB  - Self-evaluations of health status have been shown to predict mortality, above and
      beyond the contribution to prediction made by indices based on the presence of
      health problems, physical disability, and biological or life-style risk factors.
      Several possible reasons for this association are discussed: (a) methodological
      shortcomings of previous studies render the association spurious; (b) other
      psychosocial influences on mortality are involved and explain the association;
      and (c) self-evaluations of health status have a direct and independent effect of
      their own. Four-year follow-up mortality data from the Yale Health and Aging
      Project (N = 2812) are used to explore these possibilities. The analysis controls
      for the contribution of numerous indicators of health problems, disability and
      risk factors, and also makes adjustments of standard errors for the complex
      sample design. The findings favor the third possibility, an independent effect,
      to the extent that the particular set of psychosocial factors examined did not
      explain the basic association, and to the extent that the control variables were
      an adequately comprehensive set.

PMID- 1997586
TI  - Stressful events and life satisfaction among elderly men and women.
AB  - The purpose of this study was to examine the interrelationships among stressful
      events, domain-specific assessments of life satisfaction, and global evaluations
      of life satisfaction. This research was guided by two competing theoretical
      formulations. According to bottom-up theory, older adults first assess feelings
      of satisfaction within specific life domains that are based in part on the
      experiences (i.e., stressors) they encounter in these areas. The domain-specific
      views are subsequently synthesized to form an overall sense of satisfaction with
      life as a whole. In contrast, the top-down theory suggests that a person's
      ongoing sense of satisfaction with life as a whole predisposes him or her to
      assess satisfaction with specific domains in ways that are congruent with his or
      her initial sense of global life satisfaction. Analysis of data provided by older
      participants in a nationwide survey tends to support the bottom-up perspective.

PMID- 1997585
TI  - Levels of disability among U.S. adults with arthritis.
AB  - This article studies the excess levels of disability experienced by persons with
      arthritis, compared to persons without the disease. The data set is the
      Supplement on Aging (1984 National Health Interview Survey); it has information
      for a national probability sample of community-dwelling persons ages 55 + (N =
      16,148). (1) Arthritis people have more difficulty in physical functions,
      personal care, and household care than do nonarthritis persons. The excess
      disability is greatest for physical functions (walking, reaching, stooping,
      etc.). Disabled arthritis people have especially high degrees of difficulty in
      physical activities that require endurance and strength. (2) Various models are
      tested for walking, grasping, shopping, and light housework to show how
      comorbidity propels disability for arthritis people and to show arthritis' own
      contribution to disability in the presence of other chronic conditions.
      Difficulties escalate for arthritis people when they have other concurrent
      conditions. These models affirm that arthritis has a pronounced effect on
      physical dysfunctions, but these are not readily translated into personal and
      household care problems. Apparently, arthritis people often make successful
      accommodations so their roles and daily activities are not seriously affected by
      the disease.

PMID- 1997587
TI  - Work after cessation of career job.
AB  - The behavior of workers who have left full-time employment on their career jobs
      is examined using a multinomial logit technique and data from the Retirement
      History Study. Four distinct patterns of post-career job employment behavior were
      identified, with key policy and economic variables affecting the different
      decisions in distinct ways. Higher market wages were found to increase the
      probability of full-time employment, while wealth was found to reduce the
      probability of this type of employment. Employer pension benefits were found to
      reduce the probability of any type of future employment, while Social Security
      benefits led to an increase in the probability of part-time work. The results of
      this research imply that recently proposed and enacted policy will have little
      effect on the retirement decision.

PMID- 1997588
TI  - Frequency and inheritance of A and B blood types in feline breeds of the United
      States.
AB  - Using a simple hemagglutination assay to determine A and B blood types, we
      surveyed 1,072 domestic short- and longhair (DSH/DLH) cats and 1,100 purebred
      cats in the United States. Data from 234 matings with 552 offspring were
      consistent with the hypothesis that feline blood types A and B are due to the
      action of two different alleles at the same gene locus and that A is completely
      dominant over B. Neither an AB nor an O type cat was encountered. No type B cats
      were found in the Siamese and related breeds or in American Shorthair and
      Norwegian Forest cats. Among the breeds with type B blood, the proportion was
      lowest in DSH/DLH cats (0.0028) and variably higher in Abyssinian, Birman,
      British Shorthair, Devon Rex, Himalayan, Persian, Scottish Fold, and Somali,
      ranging from 0.15 to 0.59. Since all type B cats have strong, naturally occurring
      anti-A alloantibodies, fatal neonatal isoerythrolyses occur in type A offspring
      of type B mothers bred to type A males. The gene frequency of the B allele and
      the proportion of mating at risk of neonatal isoerythrolysis were estimated in a
      number of breeds. In most breeds, the frequency of the B allele was less than
      0.5. Since the kittens at risk for neonatal isoerythrolysis always have the
      genotype AB, there is constant natural selection against heterozygotes.
      Heterozygote disadvantage in the cat AB system represents an unusual form of
      negative selection, similar to that in Rh blood group incompatibility in humans.

PMID- 1997589
TI  - Genetic study of eye cancer in cattle.
AB  - Heritabilities, phenotypic, and genetic correlations of lid and corneoscleral
      pigment and eye lesions associated with "cancer eye" were investigated in 2,831
      Herefords from 34 herds in 21 states and one Canadian province. The results
      indicated that lid and corneoscleral pigment were heritable and genetically
      correlated. Corneoscleral pigment had a direct protective effect on lesions
      developing at the corneoscleral junction. Corneoscleral pigment and lesion
      development were apparently not genetically related, and lesion development was
      not heritable. These findings lead to the general conclusion that the genetic
      effect on pigment determines to a large extent the degree to which the eye is
      susceptible to some carcinogenic agent. The ultraviolet light component of
      sunlight is the most plausible carcinogenic agent that affects the eye. A genetic
      environmental interaction is indicated, whereby an increasing amount of pigment
      lessens both susceptibility and the probability of lesion development, but
      whether lesions develop in the absence of pigment depends to a large extent on
      the amount of ultraviolet light to which the eye is exposed. The findings further
      indicate that the disease is controllable by selective breeding for increased
      amounts of lid pigment, which should lead to a correlated increase in lid and
      corneoscleral pigment and a decrease in lesions.

PMID- 1997591
TI  - Estimating meiotic disjunction frequencies in chicken translocation heterozygotes
      based on embryonic mortality.
AB  - Chickens heterozygous for a chromosomal translocation [MN t(1;4)] were
      intercrossed and the progeny were analyzed for their chromosome complement. A
      ratio of 1 homozygous translocation carrier to 4 heterozygous translocation
      carriers to 1 homozygous standard chromosome carrier was noted (n = 520), rather
      than the 1:2:1 ratio expected from Mendelian segregation. The excess of
      heterozygous carriers was apparently caused by union of complementary
      duplication/deficient gametes. Embryonic death occurred in 68% of fertile
      zygotes. This finding fits very closely to expectations if alternate and adjacent
      meiotic disjunctions occurred at equal frequencies. As alternate disjunction
      frequencies increase from 0.5 to 1.0 in inter se matings, the proportion of
      inviable zygotes among fertilized ova will decrease from 0.625 to 0 and the
      proportion of translocation heterozygotes among viable progeny will decrease from
      0.667 to 0.5. In instances where alternate and adjacent disjunction occur at
      equal frequency, preferential recovery of translocation carriers will occur. This
      may contribute to chromosomal diversity within a species, and possibly lead to
      speciation.

PMID- 1997590
TI  - MHC coded B-G homodimer and heterodimer heterogeneity among different chicken
      lines.
AB  - Chicken lines were classified into six distinct groups based on expression of B-G
      molecules by peripheral red blood cells (RBC). In addition to the previously
      reported 48 kD subunits of homodimeric B-G molecules, subunits of 60, 40, and
      possibly 20 kD were detected in certain of the chicken lines. Several of the
      chicken lines express the previously reported 40 and 44 kD subunits of
      heterodimeric B-G molecules; however, B21B21 chickens expressed 44 kD subunits
      only and B5B5 and B13B13 chickens did not express detectable levels of any
      heterodimeric-related molecules. These studies provide further evidence for the
      polymorphic nature of the B-G antigens.

PMID- 1997592
TI  - Recessive inherited doubling of the chicken's uropygial gland papilla.
AB  - A new mutation that causes doubling of the uropygial gland (oil gland) papilla is
      described, and data that demonstrate its inherited basis are presented. This
      condition, which has been given the name "double oil gland papilla," varies in
      its expression: some individuals show only an indention of the papilla tip, while
      others exhibit a complete cleavage of the papilla such that two completely
      separate papillae project from a single oil gland. The data presented show that a
      single autosomal recessive gene, dgp, is the main determinant of this trait, but
      that its expression may also be influenced by background genetic factors as well
      as sex. Males more frequently are of the extreme doubling expression while
      females more frequently express the milder indented phenotype. Approximately 4%
      of mutant females are classified as normal. A linkage test with the rose comb
      gene showed independent segregation.

PMID- 1997593
TI  - The question of natural selection against mutable-to-terminator codons.
AB  - Codons that differ from a terminator triplet by only a single base are sometimes
      thought, because of their greater risk of undergoing a harmful mutation, to be
      kept at a reduced frequency by natural selection. The present study on human
      genes shows that these codons are infrequent, but their low frequency is not
      directly related to their risk of mutation to terminator. Rather, it is a
      consequence of their ending in A or G; comparable A-ending and G-ending codons
      that are not mutable to terminator are also infrequent. Natural selection does
      not appear to have depressed the frequency of mutable-to-terminator codons by
      directly eliminating some of them individually. It may have depressed their
      frequency indirectly by adjusting mutation rates in the population so that most
      of the purine-ending codons--and consequently most of the mutable-to-terminator
      ones as well--are infrequent.

PMID- 1997594
TI  - The gene for aromatase (P450arom) in the chicken is located on the long arm of
      chromosome 1.
AB  - An 125I-labeled partial cDNA for the chicken aromatase P450 was used for in situ
      hybridization to chromosomes from primary chicken embryo fibroblast cultures. The
      results indicate that the gene that encodes aromatase is located on the long arm
      of chromosome 1 at approximately position 0.16.

PMID- 1997595
TI  - A program to optimize the design of oligonucleotides for PCR amplification.

PMID- 1997596
TI  - Mycosis fungoides--a treatment review.

PMID- 1997597
TI  - Propranolol for treatment of agitation in senile dementia.
AB  - Agitated and disruptive behavior is a common complication of senile dementia.
      Therapy with antipsychotic and anxiolytic agents is frequently unsuccessful and
      problematic. Though there are no controlled studies, Propranolol, the non
      specific beta blocker, suppresses agitated behavior in patients with senile
      dementia.

PMID- 1997598
TI  - Chondroid chordoma: case report and literature review.
AB  - The case of a 74-year-old woman with chondroid chordoma is presented. This tumor
      is an uncommon variant of typical chordoma and occurs in less than 1% of all
      intracranial tumors. The mean age of occurrence is approximately 36 years, 38
      years younger than the woman in this study. Classical symptoms of intracranial
      chordoma were noted in this patient, including headaches, diplopia, third nerve
      palsy and sixth nerve palsy. Differentiation of this tumor from classic chordoma
      is important because chondroid chordoma has a substantially superior progress.

PMID- 1997599
TI  - The do-not-resuscitate decision as an advance rather than terminal decision.

PMID- 1997600
TI  - Osteoarthritis of the distal interphalangeal joint.

PMID- 1997601
TI  - From the museum.

PMID- 1997602
TI  - Mothers and infants, nurses and nursing: Alfred Donne and the medicalization of
      child care in nineteenth-century France.

PMID- 1997603
TI  - Was nervous consumption a precursor of anorexia nervosa?

PMID- 1997604
TI  - Belated progress: the enactment of eugenic legislation in Georgia.

PMID- 1997605
TI  - Patterns of disease among World War II prisoners of the Japanese: hunger, weight
      loss, and deficiency diseases in two camps.

PMID- 1997606
TI  - James Joyce: seronegative arthropathy or syphilis?

PMID- 1997607
TI  - [The early changes in bone mineral metabolism due to radiation--measurement of
      bone mineral density in lumbar vertebra by quantitative computed tomography].
AB  - Osteosclerosis, osteonecrosis and compression fracture are commonly observed
      several years after radiation. Since lumbago usually occurs several months after
      radiation, the possibility that bone mineral metabolism is disturbed during and
      immediately after radiation cannot be ruled out. However, there have been no
      reports concerning early changes in bone mineral metabolism due to radiation. The
      bone mineral density was measured by QCT (Quantitative Computed Tomography) in 30
      normal non-radiated cases and 14 radiated cases to investigate the changes in
      bone mineral metabolism due to radiation. The bone mineral density (QCT-Value:
      QCT-V) in the 3rd lumbar vertebra (L3) of normal non-radiated subjects decreased
      linearly with age (Y = 291.114447-3.01473X). The QCT-V of the 5th lumbar vertebra
      (L5) of normal cases also decreased linearly with age (Y = 309.641397-3.03986X),
      resembling that of L3. The ratio of the QCT-V of L5 to L3 (L5/L3, expressed as a
      percentage) definitely increased with age (Y = 86.5657441 + 0.58885064X). In
      radiated cases, the QCT-V of L3 in the non-radiated field did not change
      appreciably. The QCT-V of L5 in the radiated field was decreased from 20GY and
      reached 53.08 +/- 17.37% of the pre-radiation value after 50GY. The L5/L3 ratio
      was also decreased from 20GY and reached 55.47 +/- 15.32% of the pre-radiation
      value after 50GY. It becomes apparent that the QCT-V of the radiated lumbar
      vertebra is decreased during radiation. It is suggested that bone mineral
      metabolism may be disturbed in the early phase of radiation.

PMID- 1997608
TI  - [Role of magnetic resonance imaging (MRI) in evaluation of the extension of
      endometrial carcinoma].
AB  - The extent of endometrial carcinoma in Magnetic Resonance Imaging (MRI) was
      compared with that of histopathological findings. There was a significant
      positive correlation between the MRI values and the measured tissue specimen
      values for the minimum thickness of the residual myometrium (r = 0.8608; p less
      than 0.001). Twenty patients in the present study were divided into two groups
      according to myometrial invasion. Six patients (Group A) met the following
      criteria: (1) the area occupied by a high intensity lesion in the uterine body in
      the sagittal image is 50% or less, (2) the area occupied by a high intensity
      lesion in the uterine body in the transverse image is 50% or less, (3) the
      minimum thickness of the myometrium is 0.5 cm or more, and (4) the maximum
      minimum ratio of myometrial thickness is 0.5 or more. Fourteen patients (Group B)
      did not meet these conditions. Myometrial invasion of carcinoma exceeding 1/3 of
      the myometrial thickness was not observed in any patient in Group A. A
      significantly greater percentage (86%) of Group B patients had myometrial
      invasion. Vessel permeation of carcinoma and metastasis was detected in 5 and 2
      patients in Group B, respectively, but no patient in Group A had either vessel
      permeation or metastasis. A junctional zone was seen in 10 of 20 patients, and
      the carcinomatous lesions were limited to the endometrium in 2 patients, in which
      the junctional zone was not disrupted. In the other 8 patients, the localization
      of disruption of this zone corresponded to that of myometrial invasion. The
      sensitivity, specificity, and accuracy of MRI evaluation in the presence or
      absence of cervical involvement were 0.71, 0.92 and 0.85, respectively.

PMID- 1997609
TI  - Protein kinase C activity and protein phosphorylation in mouse sperm.
AB  - It has been suggested that the Ca2+ and phospholipid dependent protein kinase
      (protein kinase C; PKC) plays some intermediary roles in the regulation of the
      zona pellucida-induced acrosome reaction in mouse sperm. We here demonstrated
      that PKC activity is in the cytosol fraction of mouse sperm and that treatment of
      sperm with a PKC activator, 12-O-tetradecanoyl phorbol 13-acetate (TPA), induces
      translocation of PKC to the membrane fraction. Treatment of epididymal sperm with
      20 ng/ml TPA or 20 microM of the Ca2+ ionophore A23187 did not induce any
      specific protein phosphorylation. However, two specific proteins, with molecular
      weights of 215 kDa and 35 kDa, were significantly phosphorylated when sperm were
      incubated with A23187 prior to TPA treatment. A similar synergistic effect of TPA
      and A23187 was observed in Ca2+ accumulation in sperm. We also demonstrated that
      exogenous PKC purified from human pancreatic cells catalyzes the phosphorylation
      of these two proteins in vitro as well. The present data support the idea that
      the activation of PKC and subsequent protein phosphorylation are involved in the
      regulation of the zona pellucida-induced acrosome reaction.

PMID- 1997610
TI  - [Ultrasonographic diagnosis of bladder wall invasion in uterine cervical cancer].

PMID- 1997611
TI  - [The kinetics of interleukin 1 and prostaglandin concentrations in human amniotic
      fluid].
AB  - In order to understand the role of Interleukin 1 (IL-1) in human amniotic fluid
      (AF), the amount of IL-1 in normal human AF at various gestational ages was
      measured using ELISA. Materials were divided into three groups based on
      gestational ages. Group 1, less than 22 weeks (n = 16), consisted of AF samples
      which were collected by amniocentesis. Group 2, greater than or equal to 36 weeks
      (n = 54), consisted of AF samples collected transvaginally at delivery. Group 3,
      greater than or equal to 36 weeks (n = 9), transabdominally collected AF samples
      from elective cesarean section without labor. IL-1 alpha was present in AF of
      early gestational age in group 1 and appeared to increase with gestational age in
      group 3. In contrast, IL-1 beta was not detectable in either group 1 or 3.
      However, the concentration of IL-1 in group 2 was extremely high (IL-1 alpha
      201.0 +/- 299.3 pg/ml, IL-1 beta 1,024.1 +/- 1,321.9 pg/ml) when compared to the
      other groups. Moreover, the IL-1 alpha and IL-1 beta concentrations correlated
      with those of Prostaglandin E2 and F2 alpha in AF, measured by RIA. These
      findings suggest that IL-1 has an important role during pregnancy and during
      labor in particular.

PMID- 1997612
TI  - [Cyclic high dose CAP therapy by short-stay admission for ovarian malignancies-
      to increase total dose of CDDP and to improve quality of life of patients].
AB  - Since 1986, attempts have been made to improve the anti-cancer effect of
      Cisplatin (CDDP) in malignant ovarian tumor patients and their quality of life
      (QOL), by increasing single and total dose of CDDP and by short-stay cyclic
      treatment at our institution. In this study, the side effects of CDDP at high and
      low doses were compared and the effect on the QOL was analysed. Twenty ovarian
      malignant tumor patients who underwent adjuvant chemotherapy (CDDP 70 mg/m2,
      Adriamycin (ADR) 20 mg/m2, Cyclophosphamide (CPM) 200 mg/m2 given every 4 weeks
      for a total of 5 times and every 8-12 weeks thereafter for 5 times) after initial
      surgery were compared with non randomized control patients who received the old
      regimen of of our institution (CDDP 35 mg/m2, ADR 20 mg/m2, CRP 200 mg/m2, 5-FU
      150 mg/m2 for 5 days given every 4 weeks for a total of 5 times without discharge
      from hospital). There was no significant difference between the groups in the
      white blood cell (WBC) count and creatinine clearance (Ccr) throughout the
      treatment, although a slight drop was observed after the second course in both
      groups. The QOL was examined by interviewing the patients on their physical and
      mental condition. Although the total amount of CDDP was increased from 175 mg/m2
      to as much as 700 mg/m2, no severe nephrotoxicity or myelosuppression was seen
      and patients felt better and preserved a good QOL during a short hospital stay.
      These results clearly indicate the efficacy of our new regimen.

PMID- 1997613
TI  - [The relation between granulocyte elastase activity in cervical mucus and
      gestational cervical polyp].
AB  - Granulocyte elastase activity in cervical mucus (elastase activity) was measured
      in pregnant women (10-20 gestational weeks) with cervical polyp and controls
      (gravida with no cervical polyp). Elastase activity in the cervical polyp group
      was 86 +/- 44 U/l, and that in the control group was 22 +/- 13 (p less than
      0.01). Elastase activity after polypectomy was 44 +/- 24. It decreased
      significantly compared with prepolypectomy (p less than 0.05). A high level of
      elastase activity continued in cases without polypectomy. Immunohistochemical
      staining of elastase for cervical polyps was also performed. In the low elastase
      staining group there was low elastase activity (46 +/- 26 U/l). Elastase activity
      in the moderate staining group was 89 +/- 31, and that in the intense staining
      group was 114 +/- 31. As for the prognosis of patients with cervical polyps, the
      occurrence rate of chorioamnionitis is 9% in the control group, 14% in the polyp
      with polypectomy group and 40% in the polyp without polypectomy group. There was
      a significant difference between the polyp without polypectomy group and other
      groups (p less than 0.01). These data suggest that cervical polyp is a focus of
      inflammation and that it may cause chorioamnionitis. We conclude that cervical
      polyp during pregnancy should be removed. If polypectomy could not be performed,
      local anti-inflammatory and anti-infectious therapy would be needed.

PMID- 1997614
TI  - [Comparison between FIGO old and new staging criteria of endometrial carcinoma].
AB  - FIGO proposed new criteria for corpus cancer staging in 1988. One hundred and
      seventy-one cases of endometrial cancer were classified by these new staging
      criteria, and differences between grouping and survival rates for the new and old
      criteria were compared. 1) The number of cases grouped in old stages I, II, III
      and IV were 67, 86, 8 and 10, whereas those for new criteria 94, 25, 35 and 10,
      respectively. In 7 cases new staging was not possible because of preoperative
      radiation therapy and inoperability. 2) Cases of old stage I were reclassified as
      new stage I 54(80.5%), stage II 2(3.0%) and stage III 8(12.0%), and 3 cases were
      not classified. Those of old stage II were 39(45.2%), 21(24.55%), 25(29.1%) and
      1(1.2%) and old stage III were 1(12.5%), 2(25.0%), 2(25.0%) and 3(37.5%),
      respectively. 3) Survival rates for the cases with both stage I and II cancer
      were very good without any apparent difference between them. Those for new stage
      III were very poor in comparison with old stage III. 4) In cases of stage I
      according to the new criteria, the depth of myometrial invasion correlated well
      with the survival rate. The prognosis of G3 cases with myometrial invasion over
      1/2 was the poorest. 5) Survival rates among subclassifications of stages II and
      III were not significantly different from each other.

PMID- 1997615
TI  - [Clinicopathological analysis of endometrial carcinoma in young women].
AB  - Endometrial carcinoma in 40 women under 40 years of age (group A), was analyzed
      clinicopathologically in comparison with that in 126 women over 50 years of age
      (group B). 1. The incidence of endometrial carcinoma in women under 40 years of
      age tends to increase. 2. Sixteen (41.0%) of 39 patients in group A had
      adenoacanthoma, while 28 (23.7%) of 118 patients in group B had it. The tumor in
      group A was characterized by less myometrial invasion, lower metastatic potential
      and coexisting endometrial hyperplasia than that in group B. 3. In group A,
      patients having ovaries with corpus luteum were characterized by less coexisting
      endometrial hyperplasia and more myometrial invasion than patients having ovaries
      without corpus luteum.

PMID- 1997616
TI  - [Clinicopathological, ultrastructural and immunohistochemical study on adenoma
      malignum of the uterine cervix].
AB  - A histological, cytological, immunohistochemical and electron microscopical study
      has been made on 9 cases of adenoma malignum of the cervix. Five patients out of
      9 who received surgical treatment following correct diagnosis, and were followed
      by maintenance chemotherapy with tegafur have survived without evidence of
      recurrence for 15 to 60 months. The remaining 4 patients who were treated
      following incorrect diagnosis have died of the disease. Adenoma malignum is a
      potentially malignant tumor histologically characterized by adenomatous
      proliferation with structural abnormality in the shape and arrangement of the
      gland and budding invasive pattern into the stroma. The gland filled with mucous
      substance often ballooned and ruptured resulting in the leakage of mucous
      substance into the surrounding stromal tissue. Light and electron microscopical
      observation of the epithelial cells revealed that they were quite different from
      those of conventional adenocarcinoma. Excessive mucus-producing activity and
      variation in nuclear DNA content can lead to possible differential cytodiagnosis
      between tumorous and normal columnar cells. The finding of positive CEA in the
      cytoplasm of the tumor cell obtained in the immunohistochemical study led to
      further study to detect CEA in the cervical mucus in screening for this rare
      tumor.

PMID- 1997618
TI  - [Clinical evaluation of pseudosinusoidal fetal heart rate pattern associated with
      abruption placentae].
AB  - From retrospective studies of fetal heart rate records on abruption placentae,
      six cases with the pseudosinusoidal FHR pattern (pseudosinusoidal pattern) are
      reported. The pseudosinusoidal pattern has the following characteristics: 1)
      oscillation frequency synchronized with the frequency of uterine contractions, 2)
      an amplitude of 19bpm or more, which is positively correlated with the area of
      placental separation, 3) uniform frequency and amplitude, 4) a frequency of 1.3
      cycles/min or less, which is clearly different from the true sinusoidal pattern.
      It seems that this characteristic pseudosinusoidal pattern appeared with
      decreased fetoplacental blood flow, which was initiated by abruption placentae
      and superimposed by uterine contractions. Since this pattern indicates
      progressive fetal jeopardy, an emergency delivery should be performed for intact
      survival.

PMID- 1997617
TI  - [Immunohistochemical studies on a new antigens associated with squamous cell
      cancer in oncogenesis of uterine cervical cancer].
AB  - We examined the localization of squamous cell cancer associated antigens (SCCAA)
      in dysplasia, cancer in situ (CIS) and microinvasive SCC of the uterine cervix,
      since detection of SCCAA in these subjects is highly effective for early
      diagnosis. Anti-squamous cell cancer associated antibody (Anti SCCAAb IgG) was
      prepared by immunizing rabbits with specific components at around PI 6.1 that
      were originally purified from SCC of maxillary sinus. In this study, the
      following results were obtained by the immunoperoxidase method. (1) Eleven out of
      15(73%) cases of dysplasia, 20 out of 26(77%) cases of CIS, 21 out of 24(88%)
      cases of Stage I, 13 out of 14(93%) cases of Stage II and 9 out of 10(90%) cases
      of Stage III-IV in the clinical stages of SCC showed positive staining, while
      controls of unrelated SCC were almost negative. (2) The SCCAA positive ratio was
      2 out of 2 cases of small cell nonkeratinized type, 86% in large cell
      nonkeratinized type and 94% in Keratinized type of SCC. (3) The SCCAA was
      demonstrated on all the layers of stratified squamous epithelium in a lesion of
      CIS and some layers migrated to adjacent nonneoplastic lesion with lateral
      invasion in middle layer. These results suggest that the demonstration of SCCAA
      may be useful in diagnosing the malignant transformation of squamous epithelium
      in the early stage of SCC.

PMID- 1997619
TI  - [The role of angiotensin in paracrine interaction between rat anterior pituitary
      cells].
AB  - The present study was undertaken to investigate the role of angiotensin II (AII)
      in GnRH-induced prolactin (PRL) release from anterior pituitary cells of young
      male rats. The anterior pituitary glands were enzymatically dispersed, and
      subsequently the cells were allowed to reaggregate for 48 hours. Twenty-min
      perifusion with 100 nM GnRH increased PRL release (p less than 0.01) from the
      anterior pituitary cell aggregates. The integrated value for PRL release was 9.1
      +/- 2.9 ng/10(7) cells. The release of angiotensin I (AI) from these perifused
      pituitary aggregates was significantly increased by GnRH. In contrast, GnRH
      stimulated release of PRL was significantly suppressed by saralasin, a specific
      AII antagonist, whereas saralasin did not attenuate GnRH-induced LH release from
      these aggregates. These data demonstrate that GnRH is capable of stimulating PRL
      release through a mechanism that may involve the release of angiotensin.

PMID- 1997620
TI  - [Study on the stereo-architectural changes in human placental villi of toxemia of
      pregnancy].
AB  - Architectural changes in placental villi in clinical types of toxemia of
      pregnancy which were divided into four groups according to the main maternal
      symptoms (hypertension: H type, proteinuria: P type, PH type and IUFD) were
      studied by scanning electron microscopy and computerized image analysis of serial
      paraffin step sections. Furthermore plastic casts of villous capillaries were
      compared and changes in endothelial cells of villous capillaries were observed by
      transmission electron microscopy. 1) Scanning electron microscopy showed
      characteristic differences between P type cases and H type cases. Terminal villi
      were markedly reduced in number and showed few branches especially in P type
      cases, whereas in H type cases slender terminal villi were observed. The surface
      structure showed rough degenerative microvilli in H type cases and slender long
      microvilli in P type cases. 2) Average diameters of terminal branches estimated
      by image analysis were as follows: Normal cases: 24.8 mu, P type: 23.1 mu, H
      type: 17.9 mu, PH type: 17.7 mu, IUFD: 13.8 mu. The reduction in the number of
      intermediate villi in cases of toxemia of pregnancy was about 58% of that of
      normal cases. 3) Plastic casts of villous capillaries emphasized these changes in
      each type. 4) Swelling of the endothelial cell into the capillary lumen was
      observed and an increase in the number of filamentous structures in the cytoplasm
      of endothelial cells was detected by transmission electron microscopy.

PMID- 1997621
TI  - [Role of X-ray CT in the evaluation of extension of ovarian cancer].
AB  - To evaluate the utility of X-ray computed tomography (CT) in the management of
      malignant ovarian tumor, preoperative CT of 89 patients with ovarian cancer were
      analyzed on the basis of their surgically confirmed findings. Relationships
      between CT findings and clinical factors such as actual tumor spread, stage, and
      accomplished surgery were studied. The results obtained were as follows. 1. The
      rates of correct diagnosis in tumor spread were 79.8% for tumor growth on the
      external surface of the ovary, 77.6% for involvement of both ovaries, 79.8% for
      ascites, 78.2% for metastasis to the uterus, 68.2% for peritoneal metastasis,
      77.0% for metastasis to the intestine, and 79.3% for the metastasis to the
      omentum. 2. Comparing the stage suggested by CT (CT stage) and the stage revealed
      by surgery (surgical stage), the stages coincided in 57 patients (64.0%). CT
      stages were overestimated in 9 cases and underestimated in 23 cases. 3. As for
      the practicability of surgery, either complete or standard operation was
      performed in 31 of 33 cases (93.9%) of CT stage I, 21 of 28 (75.0%) of CT stage
      II, and 11 of 28 (39.3%) of CT stage III. The possibility of accomplishing
      surgery was very low when CT indicated stage III disease.

PMID- 1997622
TI  - [88th Symposium of the Japanese Society of Internal Medicine. April 3, 4, 5,
      1991, Kyoto City, Japan. Abstracts].

PMID- 1997623
TI  - An educator's guide to Tourette syndrome.

PMID- 1997624
TI  - Overlapping symptoms of substance abuse and learning handicaps: implications for
      educators.
AB  - The effects of substance abuse have produced a population of students who exhibit
      behaviors similar to the behaviors of many youth with learning problems. Often
      such students are mislabeled as learning handicapped (including learning
      disability, behavioral disorder, and attention deficit/hyperactive disorder),
      when their primary problem is actually one of chemical abuse. The following
      issues are examined: (a) overlapping symptoms of chemical impairment and learning
      handicap that may result in misdiagnosis, (b) student populations at high risk
      for chemical abuse, (c) preventive measures, and (d) intervention and treatment
      for chemically impaired students.

PMID- 1997625
TI  - Cognitive ability and everyday functioning in women with Turner syndrome.
AB  - This paper presents results from an assessment of cognitive ability and everyday
      functioning in a group of adult women with Turner syndrome (TUS). Twenty-three
      TUS women were compared with 23 matched controls with constitutional short
      stature (CSS). A subgroup of 10 TUS women were compared with their nondisabled
      female siblings. On the Wechsler Adult Intelligence Test-Revised (Wechsler,
      1981), no significant group differences were found in Verbal IQ. There were
      significant group differences for Performance IQ and Full Scale IQ, largely due
      to specific deficits in the area of spatial and mathematical ability. These
      difficulties were also evident on the Benton Visual Retention Test-Revised
      (Benton, 1974). TUS individuals had significantly lower educational attainment
      than CSS controls but did not differ from their siblings. TUS individuals had
      significantly lower occupational attainment than the women in both comparison
      groups.

PMID- 1997626
TI  - Dyslexia and optometric vision therapy.

PMID- 1997627
TI  - Factors associated with employment success among youths with learning
      disabilities.
AB  - This follow-up study examines the employment success of young adults with
      learning and other mild disabilities. The study questioned the employee with
      disabilities, his or her parents, and the employer on a number of vocationally
      related items. A four-factor model is advanced to explain job success. The
      factors include job match and accommodation, social acceptance, work attitude,
      and special services. Participants in a total of 41 job situations were queried
      with 38 completed triads (employee with mild disability, employer, family). The
      method of constant comparative analysis was used to analyze the data. Although an
      aggregate of the four factors correlated significantly (p less than .01), job
      match proved to have the most significant (p less than .01) relationship with the
      outcome variable. The results are interpreted in light of the need to deliver and
      understand the types of supported employment services for adults with mild
      disabilities.

PMID- 1997628
TI  - Neuropsychological stability and prognosis of subgroups of children with learning
      disabilities.
AB  - A sample of 74 Finnish children with mild learning disabilities (LD) and 57
      controls was followed from the third grade (Study 1) to the sixth grade (Study
      2). In the initial study, the sample had been grouped into five valid subgroups
      (Normal, General Language, Visuo-Motor, General Deficiency, Naming) utilizing a
      cluster analysis. In both studies a battery of 12 neuropsychological, reading,
      and writing tests was administered, and teacher ratings were obtained. The
      results indicated that the general neuropsychological profiles of the subgroups
      were maintained, but some changes, consistent with the progress in reading, were
      noted. The developmental rate of some neuropsychological functions from Study 1
      to Study 2 in the subgroups of children with learning disabilities more closely
      approached that of the Normal subgroup. At follow-up, 64% of the original LD
      sample continued to have marked reading and/or writing problems. The Naming
      subgroup had a more unfavorable prognosis than the other subgroups, especially in
      reading, and the General Deficiency subgroup in writing (spelling), respectively.
      Some possibilities for using the results to improve remedial teaching are
      discussed.

PMID- 1997629
TI  - Detection of deficits in temporal pattern discrimination using the seashore
      rhythm test in young children with reading impairments.
AB  - A deficiency in temporal pattern discrimination frequently is a distinguishing
      characteristic of children with dyslexia or learning disabilities (LD). We
      studied the feasibility of using the Seashore Rhythm Test, a subtest of the
      Halstead-Reitan neurological assessment battery (Halstead, 1947), with young
      children to discriminate children with reading impairments from age-matched
      controls reading at a normal level, in an effort to develop tools to determine
      readiness to read in young school-age children. Major considerations in test
      selection were ease of administration and wide use and acceptance. Fifty-nine
      children in Grades 1 through 3 were administered a battery of tests during the
      last 3 weeks of the school year by blinded experimenters. Tests administered
      included the Seashore Rhythm Test, Benton Visual Retention Test, Peabody Picture
      Vocabulary Test, Blau Torque Test, and the Rod and Frame Test. Children with
      reading impairments (n = 24) in all age groups were found to exhibit a marked
      deficit in the ability to discriminate patterned pairs of tones on the Seashore
      Rhythm Test compared to controls (n = 26). These children also exhibited deficits
      in right-left orientation, as indicated by their poor performance on the Blau
      Torque Test. Performance on the Seashore and the Blau by a group of children
      diagnosed as learning disabled (n = 9) was similar to the group with reading
      impairments. No significant differences between controls and children with
      reading impairments or LD were observed in Rod and Frame or Benton performance.
      The results suggest that the Seashore Rhythm Test may prove to be a useful tool
      to detect young children who will later show signs of reading impairment.

PMID- 1997630
TI  - Effects of peer-mediated instruction on the acquisition and generalization of
      written capitalization skills.
AB  - This study investigated the effects of a peer teaching procedure, combined with
      student letter-writing activities, on the acquisition and generalization of
      capitalization skills. Three students, aged 9 years, obtained instruction from
      peer partners that included (a) an introduction and review of capitalization
      rules, (b) feedback on each participant's previous capitalization work, and (c)
      guided and independent practice on sentences that required capitalization. All
      three students demonstrated acquisition of the capitalization rules after
      participating in the teaching sessions with one or two peer partners. In
      addition, there were increases in capitalization accuracy in participants'
      letters to peers who did not serve as teaching partners, thus demonstrating a
      measure of across-peer (stimulus) generalization. Mixed results were obtained on
      a response generalization task (sentence writing). Finally, sentencing-writing
      activities also showed that two of the peer partners substantially improved their
      use of capitalization skills as a result of teaching the target students.

PMID- 1997631
TI  - Immune regulation by platelet-activating factor: II. Mediation of suppression by
      cytokine-stimulated endothelial cells in vitro.
AB  - Human umbilical vein endothelial cells (EC) can respond to endotoxin or to the
      inflammatory cytokines tumor necrosis factor (TNF) and interleukin 1 (IL-1) by
      producing platelet-activating factor (PAF). When EC were preexposed to TNF-alpha
      (25 U/ml) for 1 h, and then washed, their subsequent coculture with peripheral
      blood mononuclear cells (PBMC) resulted in suppressed proliferative response of
      the latter to the mitogen Con A (P less than 0.05). This effect was completely
      reversed by the concomitant use of the PAF receptor antagonist BN 52021 (0.1 mM).
      Preexposure of EC to IL-1 beta (0.5 U/ml) induced similar effects, but IL-1 and
      TNF were not additive. Removal of monocytes from the PBMC population abolished
      the effects. On the other hand, coculture of monocytes with cytokine-preexposed
      EC resulted in significant induction of suppressor activity on lymphocyte
      proliferation. Our data indicate that EC, preexposed to inflammatory cytokines,
      can modulate lymphocyte functions via the production of PAF and its action on
      monocytes.

PMID- 1997633
TI  - Tumor necrosis factor increases in vivo glucose uptake in hepatic nonparenchymal
      cells.
AB  - This study aims to elucidate the in vivo metabolic response of different liver
      cells following a short-term (30 min) infusion of a nonlethal dose of human
      recombinant tumor necrosis factor (TNF). In vivo glucose uptake of different
      tissues and isolated liver cells was determined by a sequential double-labeling
      version of the tracer 2-deoxyglucose technique. Following TNF administration
      glucose uptake was increased in the liver, lung, spleen, and skin while it was
      not changed in muscle and testis. In response to TNF infusion neutropenia
      developed which was sustained for 40 min. The number of lymphocytes in the blood
      was also decreased after the termination of TNF infusion. This short-term
      infusion of TNF, however, was not accompanied by marked sequestration of
      leukocytes into the liver. In vivo glucose uptake in response to TNF was doubled
      in the Kupffer cells and increased by 56% in hepatic endothelial cells. Glucose
      uptake of parenchymal cells was not significantly affected. The prompt increase
      of glucose uptake in the reticuloendothelial cells of the liver, primarily in the
      Kupffer cells, following TNF administration suggests that a similar metabolic
      response of these cells to sepsis may be mediated at least in part by TNF. It is
      suggested that the increased glucose uptake by the hepatic nonparenchymal cells
      is a reflection of the immunomodulatory effect of TNF.

PMID- 1997634
TI  - Citation frequency and journal impact: valid indicators of scientific quality?

PMID- 1997632
TI  - Chemotactic activity and receptor binding of neutrophil attractant/activation
      protein-1 (NAP-1) and structurally related host defense cytokines: interaction of
      NAP-2 with the NAP-1 receptor.
AB  - Neutrophil attractant/activation protein-1 (NAP-1) has sequence similarity to
      platelet factor-4 (PF-4) and to NAP-2 (a truncated from of connective tissue
      activating protein-III [CTAP-III(des 1-15)]. We compared chemotactic activity for
      neutrophils of these related proteins. We also included for comparison CTAP-III,
      CTAP-III(des 1-13), the C-terminal dodecapeptide of PF-4 [PF-4(59-70)], and C5a.
      Chemotactic potency (EC50) was highest for NAP-1 and C5a. Although chemotactic
      efficacy (peak percentage of neutrophils migrating) was comparable for C5a, NAP
      1, and NAP-2, the NAP-2 response occurred only at concentrations 100-fold higher
      than the NAP-1 EC50 of 10(8) M. Data for the CTAP-III proteins confirmed that
      CTAP-III is not an attractant and that chemotactic activity appears as a result
      of cleavage of residues at the N-terminus to make CTAP-III(des 1-13) or NAP-2
      [CTAP-III(des 1-15)]. Chemotactic activity of PF-4 was low and variable, with no
      significant response by neutrophils from six of nine subjects. In contrast, PF
      4(59-70) regularly induced high chemotactic responses, although the EC50 of 1.6 x
      10(5)M was 1,000-fold greater than that of NAP-1. The binding of fluoresceinated
      NAP-1 to neutrophils was inhibited by unlabeled NAP-1 or NAP-2 but not by PF-4 or
      PF-4 (59-70). This suggests that NAP-2 interacts with the neutrophil NAP-1
      receptor. Despite the low chemotactic potency of NAP-2, it is a potential
      attractant at sites of injury because of the relatively large amounts of the
      parent CTAP-III released from platelets, as indicated by a serum concentration of
      approximately 10(-6) M.

PMID- 1997635
TI  - Fifty years of progress with antithrombotic drugs--with much more to come: a
      perspective.

PMID- 1997637
TI  - Effect of recombinant human erythropoietin treatment on blood pressure and some
      haematological parameters in healthy men.
AB  - The aim of this study was to evaluate the effect of treatment with subcutaneous
      injections of recombinant human erythropoietin (rhEpo), 20-40 IU kg-1 body
      weight, 3 times a week, on resting blood pressure, blood pressure response during
      submaximal exercise, some haematological parameters, and subjective side-effects
      in 15 healthy male subjects. RhEpo increased both haemoglobin (Hb) concentration
      and haematocrit (Hct) significantly, the values for Hb being 152 +/- 4.2 g l-1
      before treatment and 169 +/- 9.3 g l-1 (mean values +/- SD) after 6 weeks of
      rhEpo treatment (P less than 0.001). The corresponding values for Hct were 44.5
      +/- 1.5% and 49.7 +/- 1.9% (P less than 0.001), respectively. The systolic and
      diastolic blood pressure values at rest were unchanged after rhEpo treatment. A
      marked increase in systolic blood pressure was observed during submaximal
      exercise at 200 W, the initial and final values being 177 +/- 14.2 mmHg and 191
      +/- 19.5 mmHg (P less than 0.01), respectively. Heart rate during exercise at 200
      W was significantly lower after rhEpo treatment than before it: 144 +/- 15 beats
      min-1 compared to 136 +/- 8 beats min-1 (P less than 0.001). The leucocyte count
      remained unchanged after rhEpo treatment, but there was a significant decrease (P
      less than 0.05) in the number of lymphocytes. Reticulocyte and platelet counts
      were unchanged. Serum (S) ferritin decreased from 87.3 +/- 41.8 mmol l-1 to 59.3
      +/- 27.8 mmol l-1 after rhEpo treatment (P less than 0.001). Serum-Na, S-K, S-Ca,
      S-creatinine, S-bilirubin, S-aspartate aminotransferase (ASAT), S-alanine
      aminotransferase (ALAT), and S-lactate dehydrogenase (LD) were unchanged after
      rhEpo treatment. No subjective side-effects were reported. In conclusion, low
      doses of rhEpo increased Hb levels and Hct by more than 10% after 6 weeks. Blood
      pressure at rest was unchanged, but rhEpo induced a markedly accentuated blood
      pressure reaction during exercise. A minor decrease in the lymphocyte count was
      observed, but electrolyte and creatinine levels remained unchanged after rhEpo
      treatment.

PMID- 1997636
TI  - Mechanical ventilation in medical and neurological diseases: 11 years of
      experience.
AB  - Mechanical ventilation (MV) is imperative in many forms of acute respiratory
      failure (ARF). The aim of this work was to review all episodes of MV in a Medical
      Intensive Care Unit (MICU) during the 11-year period 1976-1986. Four per cent (n
      = 1008) of 24,899 admissions to the MICU were treated with MV. The mean age of
      ventilator-treated patients was 53 +/- 18 years, and obviously it increased
      during the period of study. The average duration of MV was 4.7 d. MICU mortality,
      hospital mortality and 2-year mortality rates for patients subjected to MV were
      33%, 38% and 46%, respectively. The mortality rate did not change during the
      study period. Cerebrovascular and malignant diseases carried the highest
      mortality rates, 75 and 79%, respectively, whereas mortality in patients
      ventilated because of drug overdose (n = 313) was only 2%. The results of this
      study confirm previously published findings concerning the outcome of MV, and we
      conclude that the effects of MV remain discouraging in medical and neurological
      patients. Improved quality of ventilator therapy and monitoring, as well as
      continued research directed at the causes of ARF, are equally important in
      reducing the mortality in ARF.

PMID- 1997638
TI  - Diurnal variation in the levels of antidiuretic hormone in the elderly.
AB  - The secretion of antidiuretic hormone (ADH) and the serum osmolality were
      measured at 4-h intervals throughout a 24-h period in 69 healthy elderly
      volunteers. In male subjects the concentrations of plasma ADH were always twofold
      higher than in female subjects. The normal diurnal rhythm, with increased ADH
      secretion during the night, was not seen in this group of elderly subjects, with
      the exception of elderly men who did not urinate during the night, in whom a
      substantial increase in plasma ADH levels occurred. In as many as 25% of all the
      ADH measurements performed (n = 455) ADH was not detectable by the method used.
      The lack of a definite diurnal rhythm in most of the elderly subjects could to
      some extent explain the increased diuresis during the night in the elderly.

PMID- 1997639
TI  - Prostacyclin production in myocardial infarction in the acute phase and during
      follow-up.
AB  - Twenty-five patients with myocardial infarction were monitored in the acute phase
      and during follow-up with regard to the in vivo production of prostacyclin (PGI2)
      and thromboxane (TxA2), by measurement of their major urinary metabolites, 2,3
      dinor-6-keto-PGF1 alpha and 2,3-dinor-TxB2, respectively. In 22 of these patients
      PGI2 and TxA2 production were also assessed before, during and after an exercise
      test performed 6 weeks after discharge. In approximately 24% of patients the in
      vivo production of prostacyclin did not increase during the acute phase of the
      infarction process. This inability was usually associated with a decrease in the
      release of heart muscle enzymes, and was mostly frequently observed in women.
      During the exercise tolerance test, none of the patients showed any increase in
      prostacyclin production, in contrast to healthy volunteers, in whom a significant
      increase was seen. There were no differences between patients with and without an
      increase in prostacyclin production during the acute phase. At the follow-up 2
      years after the myocardial infarction, eight cardiac events had occurred, all of
      which were noted among patients who exhibited an expected increase in
      prostacyclin production in association with the infarction. This would seem
      reasonable, since most of the patients in this group had larger primary
      infarctions.

PMID- 1997640
TI  - Rapid and correct diagnosis of myocardial infarction: standardized case history
      and clinical examination provide important information for correct referral to
      monitored beds.
AB  - The value of thorough examination of the case history as a diagnostic tool on
      hospitalization of patients with suspected myocardial infarction was investigated
      in three independent prospective studies. Use of a limited number of pain-related
      elements (= 'criteria'), that had already been obtained in the emergency room,
      could improve the decision on whether or not to admit patients to the coronary
      care unit. As an example, in one of the studies, use of such criteria would have
      reduced the number of 'unnecessary' coronary-care-unit admissions from 298 to
      162, a 46% reduction (P less than 0.001). In the same patient sample, use of the
      criteria could have reduced the number of patients with definite acute myocardial
      infarction, admitted to the general wards, from 47 to 22, a 53% reduction (P less
      than 0.01). These favourable results were confirmed in the two independent,
      smaller-scale studies.

PMID- 1997641
TI  - Observer variation in the clinical assessment of the thyroid gland.
AB  - In order to evaluate the reliability of clinical assessment of the thyroid gland,
      two specialists in endocrinology and two younger doctors independently examined
      53 patients twice, and assessed whether they had a diffuse goitre, a multinodular
      goitre, a solitary nodule or a normal gland. In 30% of the patients all four
      observers were in agreement, whereas in 47% and 23% of the patients, two and
      three different diagnoses were given, respectively. Inter-observer variation was
      determined and kappa values between -0.04 and 0.54 were found. Intra-observer
      variation was smaller, revealing kappa values between 0.44 and 1.00. The present
      study suggests that clinical assessment of the thyroid gland may lead to
      misclassification of the type of thyroid disease, and thereby to a less than
      optimal choice of therapy.

PMID- 1997642
TI  - Serum creatinine: an independent predictor of survival after stroke.
AB  - We prospectively studied the relationship between serum creatinine and survival
      among 492 elderly subjects admitted for stroke and monitored for a mean period of
      18 months post-stroke. In multivariate proportional hazards models, serum
      creatinine remained an independent predictor of mortality (P = 0.0001) after
      accounting for other important predictors such as level of consciousness. Mini
      Mental State Score, age, leucocyte count, presence of heart disease, diabetes,
      heart failure, atrial fibrillation and use of cardiovascular medication. This
      association between elevated serum creatinine and mortality was also found in
      patient subgroups with CT-proven infarction and intracerebral haematoma. It is
      concluded that serum creatinine is an independent predictor of survival after
      stroke. Further studies are required to confirm this relationship and to
      elucidate the underlying mechanism.

PMID- 1997643
TI  - Pneumothorax in a patient with Wegener's granulomatosis during treatment with
      immunosuppressive agents.
AB  - We present the case of a 16-year-old woman with Wegener's granulomatosis, who
      developed a pneumothorax while receiving treatment with cyclophosphamide and
      glucocorticoids. The lung was re-expanded by tube drainage, and the patient
      recovered completely while the immunosuppressive treatment was continued in
      combination with sulphamethoxazole-trimethoprim. A possible role for this
      antimicrobial drug in the treatment of Wegener's granulomatosis is briefly
      discussed.

PMID- 1997644
TI  - Gastric lymphoma causing granulocytopenia and cold intolerance, with recovery
      after treatment.
AB  - A 34-year-old man was found to have granulocytopenia with a white blood count of
      2.3 x 10(9) l-1, consisting of 10% segmented neutrophils, 50% monocytes and 40%
      lymphocytes. A bone marrow aspirate showed 20% promyelocytes and 10% blasts with
      monoblastic features, and a smouldering myelomonocytic leukaemia was considered
      to be a possible diagnosis. In cold weather the patient experienced cold
      intolerance with acrocyanosis and small ulcerations on the ears. The test for
      heparin-precipitable protein ('cryofibrinogen') was strongly positive. During the
      following year, these signs and symptoms persisted, and the patient also
      developed constant moderate pain in the epigastric region. Gastroscopy revealed a
      large lymphoma of the stomach, which was a high-grade malignant centroblastic
      type of non-Hodgkin's lymphoma. After successful removal of the tumour, and six
      courses of potent cytostatic combinations, the patient recovered completely, and
      the granulocytopenia and cold intolerance disappeared.

PMID- 1997645
TI  - Familial hypobetalipoproteinaemia complicated by cerebellar ataxia and
      steatocystoma multiplex.
AB  - A 55-year-old man with cerebellar ataxia and steatocystoma multiplex was found to
      have reduced serum concentrations of total cholesterol, betalipoprotein and
      apolipoprotein B. Computed tomography revealed atrophy of the cerebellum and
      brain stem. Of the six family members examined, four had
      hypobetalipoproteinaemia, and one had mild ataxia. Similar skin lesions were
      noted in five male relatives. This case represents a rare combination of familial
      hypobetalipoproteinaemia, cerebellar ataxia and steatocystoma multiplex.

PMID- 1997646
TI  - ACTH 1-24 decreases hepatic lipase activities and low density lipoprotein
      concentrations in healthy men.

PMID- 1997647
TI  - Constitutive production of inflammatory and mitogenic cytokines by rheumatoid
      synovial fibroblasts.
AB  - Conditioned media obtained from fibroblasts cultured from rheumatoid and certain
      other inflammatory synovia were observed to stimulate [3H]thymidine incorporation
      in an indicator murine fibroblast line. Synovial fibroblasts derived from the
      joints of patients with osteoarthritis did not display this property. This effect
      persisted in culture for many weeks and occurred in the absence of co-stimulatory
      immune cells. Antibody neutralization studies implicated a role for basic
      fibroblast growth factor (bFGF), transforming growth factor beta (TGF-beta),
      granulocyte/macrophage colony-stimulating factor (GM-CSF), and interleukin 1 beta
      (IL-1 beta) in the increased proliferative activity of synovial fibroblast
      conditioned media. Synovial cell synthesis of bFGF, TGF beta 1, GM-CSF, IL-1
      beta, and IL-6 was confirmed by 35S-methionine labeling and immunoprecipitation.
      The constitutive production of inflammatory and mitogenic cytokines by synovial
      fibroblasts may represent the result of long-term, phenotypic changes that
      occurred in vivo. Persistent cytokine production by synovial fibroblasts may play
      an important role in the continued recruitment and activation of inflammatory
      cells in chronic arthritis and in the formation of rheumatoid pannus.

PMID- 1997648
TI  - Evidence for a role of the integrin VLA-4 in lympho-hemopoiesis.
AB  - Adhesion molecules are probably required for retention of maturing lymphocyte
      precursors in bone marrow, where they closely interact with and are dependent on
      stromal cells. Lymphomyeloid cell lines avidly adhere to cloned stromal cell
      lines in culture and screening pairs of these resulted in a selection strategy
      for a new monoclonal antibody to a leukocyte adhesion molecule.
      Immunoprecipitation analyses and comparison to a previously described antibody
      showed that it recognizes the alpha 4 chain of the integrin, VLA-4. This antibody
      totally inhibited lymphopoiesis and retarded myelopoiesis in long-term bone
      marrow cultures. A similar selection strategy resulted in two additional
      antibodies which define a single 100-kD species on stromal cells. This stromal
      cell adhesion molecule is a potential counter-receptor/ligand for VLA-4 on murine
      lympho-myeloid cells. Our findings suggest a new role for VLA-4 in lymphoid
      progenitor-microenvironment interactions. Recognition molecules that function in
      cell migration and inflammation in peripheral tissues may be important for steady
      state lymphopoiesis within bone marrow.

PMID- 1997650
TI  - An isotype-specific trans-acting factor is defective in a mutant B cell line that
      expresses HLA-DQ, but not -DR or -DP.
AB  - The B lymphoblastoid cell line clone 13 (a subclone of the mutant cell line P3JHR
      1) has been found to express high levels of HLA-DQ; by contrast, HLA-DR and -DP
      antigens are not expressed and cannot be induced by interferon gamma. Northern
      blot analysis using gene-specific probes indicated that the lack of surface
      expression of the DR and DP antigens is due to a marked decrease in the levels of
      steady-state RNA for both the alpha and beta chains. Southern blots demonstrated
      that none of the transcriptionally repressed genes are grossly deleted.
      Preparations of interspecific transient heterokaryons between clone 13 and the
      class II antigen-positive murine B cell lymphoma, A20, resulted in reactivation
      of the DRA gene and surface expression of both the DR and DP molecules. The
      efficiency of the DRA promoter relative to the DQB promoter is markedly and
      specifically diminished in clone 13 (P3JHR-1) as compared with the parental cell
      line, Jijoye, as assayed both by transient expression of appropriate
      chloramphenicol acetyltransferase gene (CAT) constructs and by in vitro
      transcription analysis. These data clearly demonstrate the existence of an
      isotype-specific trans-acting factor, and provide direct evidence that the highly
      homologous class II genes have distinct regulatory mechanisms.

PMID- 1997649
TI  - Is cyclophilin involved in the immunosuppressive and nephrotoxic mechanism of
      action of cyclosporin A?
AB  - In this report we have approached two questions relating to the mechanism of
      action of cyclosporin A (CsA). First, we address whether the major cytosolic
      protein for CsA, cyclophilin, is directly involved in mediating the
      immunosuppressive activity of this drug, and, in particular, whether inhibition
      of this protein's peptidyl-prolyl cis-trans isomerase (PPIase) activity results
      in inhibition of murine T cell activation. Second, we ask whether the
      nephrotoxicity observed with CsA is related to inhibition of PPIase-dependent
      pathways in cells other than lymphocytes. Using a series of 61 cyclosporin
      analogues, we generally found a good correlation between cyclophilin binding and
      immunosuppressive activity for the majority of analogues analyzed. However, a
      number of compounds of distinct structural classes were found that could interact
      with cyclophilin but were much less immunosuppressive than expected. The
      inability of these analogues to inhibit lymphocyte activation could not be
      explained by their failure to enter the cell and bind to cyclophilin under the
      conditions used in the cellular assays. Surprisingly, a nonimmunosuppressive
      analogue, MeAla-6, which bound well to cyclophilin and was active as a PPIase
      inhibitor, did not induce renal pathology in vivo. Furthermore, another analogue,
      MeBm2t, which was immunosuppressive in vitro, possessed little or no activity as
      a PPIase inhibitor. These findings pose serious questions concerning a direct
      role of cyclosporin in mediating CsA's immunosuppressive and nephrotoxic
      activities. In addition, they raise doubts about whether PPIase has a direct
      function in lymphocyte signal transduction.

PMID- 1997651
TI  - The immunodeficient scid mouse as a model for human lymphatic filariasis.
AB  - The C.B.-17-scid/scid mouse (hereafter referred to as the scid mouse) is
      homozygous for a recessive mutation at a locus that influences the assembly of
      intact immunoglobulin and T cell receptor genes. Therefore, scid mice cannot
      generate functional B or T lymphocytes, are profoundly immunodeficient, and have
      been reported to be receptive to reconstitution with human immune cells. In the
      present study, we injected scid mice with infective larvae of the human filarial
      parasite Brugia malayi. Within 6-10 wk after subcutaneous injection of infective
      L3 larvae, both male and female worms were observed in various stages of
      development in 90% of the mice. In animals tested 8 weeks or more after
      infection, microfilariae were detected in the blood or peritoneal cavity of 52%
      of the mice examined. Adult worms were observed in the lymphatics of the infected
      scid mice, where their presence was associated with lymphangitis and
      lymphangiectasia. These results suggest that the scid mouse model of lymphatic
      filariasis may be important in investigation of the interaction of the murine,
      and possibly the human, immune system with the lymphatic filarial parasite.

PMID- 1997652
TI  - Thalidomide selectively inhibits tumor necrosis factor alpha production by
      stimulated human monocytes.
AB  - Thalidomide selectively inhibits the production of human monocyte tumor necrosis
      factor alpha (TNF-alpha) when these cells are triggered with lipopolysaccharide
      and other agonists in culture. 40% inhibition occurs at the clinically achievable
      dose of the drug of 1 micrograms/ml. In contrast, the amount of total protein and
      individual proteins labeled with [35S]methionine and expressed on SDS-PAGE are
      not influenced. The amounts of interleukin 1 beta (IL-1 beta), IL-6, and
      granulocyte/macrophage colony-stimulating factor produced by monocytes remain
      unaltered. The selectivity of this drug may be useful in determining the role of
      TNF-alpha in vivo and modulating its toxic effects in a clinical setting.

PMID- 1997653
TI  - Human B cell clones can be induced to proliferate and to switch to IgE and IgG4
      synthesis by interleukin 4 and a signal provided by activated CD4+ T cell clones.
AB  - In the present study, it is demonstrated that cloned surface IgM-positive human B
      cells can be induced to proliferate and to switch with high frequencies to IgG4
      and IgE production after a contact-mediated signal provided by T cell clones and
      interleukin 4 (IL-4). This T cell signal is antigen nonspecific and is provided
      by activated CD4+ cells, whereas activated CD8+ or resting CD4+ T cell clones are
      ineffective. 15-35% of the B cell clones cultured with cloned CD4+ T cells and IL
      4 produced antibodies; 35-45% of those wells in which antibodies were produced
      contained IgE and IgG4. In addition to B cell clones that produced IgG4 or IgE
      only, B cell clones producing multiple isotypes were observed. Simultaneous
      production of IgG4 and IgE, IgM, IgE, and IgM, or IgG4 and IgE was detected,
      suggesting that during clonal expansion switching might occur in successive steps
      from IgM to IgG4 and IgE. In addition, production of only IgM, IgG4, and IgE
      during clonal expansion indicates that this isotype switching is directed by the
      way a B cell is stimulated and that it is not a stochastic process.

PMID- 1997654
TI  - High levels of CD44 expression distinguish virgin from antigen-primed B cells.
AB  - The in vitro polyclonal stimulation of B cells through their surface
      immunoglobulin (Ig) induces substantial increases in CD44 protein levels within
      24 hours, whereas other stimuli (e.g., lipopolysaccharide, phorbol 12,13
      dibutyrate, and interleukin 4) fail to significantly upregulate CD44. The marked
      increase in CD44 protein expression on anti-Ig-treated B lymphocytes correlates
      with an increase in CD44-specific mRNA. Cell sorting experiments with B cells
      isolated from trinitrophenyl-keyhole limpet hemocyanin-immunized mice demonstrate
      that both short-term antigen-specific, IgG-secreting cells and long-term antigen
      primed B cells are exclusively CD44high. We speculate that the rapid and
      sustained increase in CD44 expression mediated by surface Ig stimulation may
      alter the homing properties of antigen-primed B cells.

PMID- 1997655
TI  - Phagocytosing neutrophils produce and release high amounts of the neutrophil
      activating peptide 1/interleukin 8.
AB  - After phagocytosis of yeast opsonized with IgG, neutrophil leukocytes
      (polymorphonuclear leukocytes [PMN]) expressed high levels of neutrophil
      activating peptide 1/interleukin 8 (NAP-1/IL-8) mRNA, which peaked after 3-5 h
      and were still elevated after 18 h. A similar but quantitatively less prominent
      effect was obtained with lipopolysaccharide (LPS). After phagocytosis, but not
      after exposure to LPS, the PMN progressively released considerable amounts of NAP
      1/IL-8 into the culture medium (18.6-50 ng/ml in 18 h). The peptide released was
      biologically active, as indicated by the transient elevation of cytosolic-free
      calcium in PMN exposed to aliquots of the culture supernatants, and
      desensitization by prestimulation of the cells with recombinant NAP-1/IL-8. By
      producing NAP-1/IL-8 at sites where they phagocytose invading microorganisms, PMN
      could enhance the recruitment of new defense cells.

PMID- 1997656
TI  - Messenger RNA expression of the cytokine gene cluster, interleukin 3 (IL-3), IL
      4, IL-5, and granulocyte/macrophage colony-stimulating factor, in allergen
      induced late-phase cutaneous reactions in atopic subjects.
AB  - Cryostat sections from skin biopsies from 24-h allergen-induced late-phase
      cutaneous reactions (LPR) in 14 human atopic subjects were hybridized with 35S
      labeled RNA probes for a number of cytokines. mRNA was detected for interleukin 3
      (IL-3) (8/14), IL-4 (10/14), IL-5 (11/14), and granulocyte/macrophage colony
      stimulating factor (GM-CSF) (13/14). Only 5 of 14 gave hybridization signals for
      IL-2, and 0 of 14 for interferon gamma. Biopsies from diluent controls gave only
      occasional weak signals. These results suggest that cells infiltrating the site
      of the 24-h LPR transcribe mRNA for the IL-3, IL-4, IL-5, and GM-CSF gene cluster
      and support the hypothesis that atopy is associated with preferential activation
      of cells having a similar cytokine profile to the murine T helper type 2 subset.

PMID- 1997657
TI  - Patterns of neuropsychological impairment after severe blunt head injury.
AB  - A consecutive series of 100 subjects with severe blunt head injuries was followed
      up 6 years after trauma. Neuropsychological test performances of 82 subjects and
      of a noninjured control group were analyzed by two principal components analyses
      (PCAs). Each PCA extracted 15 factors relating to a range of cognitive
      impairments, as well as neuropsychological features consistent with posttraumatic
      personality changes. Measures identified by the PCAs were applied to 85 head
      injured subjects in the series to examine the incidence of impairment in four
      neuropsychological areas: disorders of learning and memory, neuropsychological
      features consistent with posttraumatic personality change, slowness in rate of
      information processing, and a range of basic neuropsychological skills. Overall,
      impairments occurred in 70% of the series. Disorders of learning and memory were
      the most common type of deficit (56.5%), with disturbances in basic
      neuropsychological skills the least frequent (16.5%). Variability among subjects
      with respect to the types and combinations of neuropsychological impairments was
      a characteristic feature of this clinical group, but the largest proportion (one
      third) demonstrated isolated impairments. The implications of the incidence and
      selectivity of neuropsychological impairments are discussed.

PMID- 1997658
TI  - Neuropsychological performance in patients with mild multiple sclerosis.
AB  - Although changes in cognitive function in patients with multiple sclerosis (MS)
      have been reported, these changes have been traditionally associated with the
      later stages of the disease. In the current study, a comprehensive
      neuropsychological battery was administered to MS patients (N = 86) in whom the
      disease progression was relatively mild and in remission and a demographically
      well-matched control group (N = 46). Besides the expected differences in tests of
      motor function, the two groups also differed on a number of cognitive tests with
      no motor demands. The two cognitive functions that appear impaired were learning
      and memory. Given that similar deficits have been found in MS patients with more
      severe symptoms, it is argued that changes in cognitive function can occur in the
      mild stages of the disease.

PMID- 1997659
TI  - Optical differences in multiple personality disorder. A second look.
AB  - The study was designed as a replication of a study reported in this Journal
      (Miller S [1989] Optical differences in cases of multiple personality disorder.
      J. Nerv Ment Dis 177:480-486) which found that subjects with multiple personality
      disorder (MPD) experienced significantly more changes in visual functioning
      between alter personalities than a control group simulating the disorder. In the
      present study, data from 20 patients diagnosed with MPD and 20 control subjects
      role playing MPD were analyzed for statistical and clinical significance. The
      findings from the present study appear to confirm results from the earlier study
      that individuals with MPD experience differences in some aspects of visual
      functioning between alter personalities. The results further confirm that MPD
      subjects experience more differences across visual measures than control subjects
      simulating the disorder. However, the findings from the present study are not
      entirely consistent across the various visual measures or with findings from
      previous studies.

PMID- 1997660
TI  - Psychiatric symptoms in mentally ill chemical abusers.
AB  - The purpose of this study was to determine whether mentally ill chemical abusers
      (MICA patients) report greater distress than do psychiatric patients who do not
      abuse psychoactive substances. Thirty-two MICA patients and 31 non-substance
      abusing patients completed the SCL-90-R. Group comparisons indicated that MICA
      patients reported greater levels of somatization, depression, anxiety, obsessive
      compulsiveness, paranoia, and psychotic symptoms. MICA patients also reported
      greater overall distress than did psychiatric patients without substance abuse
      problems.

PMID- 1997661
TI  - Gender roles, social support, and postpartum depressive symptomatology. The
      benefits of caring.
AB  - Although women are assumed to be particularly vulnerable to depressive
      symptomatology after childbirth, the extent to which this symptomatology
      predominates over that found in men at this life cycle stage has not been
      addressed. This study examined gender differences in postpartum depressive
      symptomatology and the link between postpartum symptomatology and gender roles
      and relationships in a sample obtained from childbirth preparation classes. The
      data show no gender difference in depressive symptomatology at 2 months after
      childbirth. Women manifested a decrease in depressive symptomatology and men
      showed a slight increase from the preparenthood point. We partially link women's
      equivalent rather than higher distress levels to the protective effects of their
      varied social supports. By contrast, men depended primarily on their spouses, but
      both genders experienced a decrease in spouse support after childbirth. Female
      lack of support was more strongly associated with symptomatology in homemakers
      compared with employed women or women on maternity leave. Within the context of
      gender role changes, the data highlight benefits of female bonding in contrast to
      the "costs of caring" depicted by other researchers.

PMID- 1997662
TI  - Dependency and eating disorders in female psychiatric inpatients.
AB  - Research indicates that oral dependent and eating-disordered individuals have
      similar personality traits, attitudes, and behaviors, suggesting that dependency
      may be a factor in the dynamics of anorexia and bulimia. To investigate this
      issue, we compared the proportions of dependent and food-related percepts in the
      Rorschach protocols of matched samples of eating-disordered (N = 16), obese (N =
      18), and non-eating-disordered, normal-weight female psychiatric inpatients (N =
      17). Eating-disordered patients reported significantly more dependent Rorschach
      imagery than did obese or normal-weight control patients, but no difference in
      the proportion of food-related imagery was found among the three groups. These
      results support the hypothesis that unresolved dependency issues underlie
      anorexia and bulimia.

PMID- 1997663
TI  - Borderline personality disorder in young Swedish suicides.
AB  - Fifty-eight consecutive suicides committed between 1984 and 1987 by adolescents
      and young adults (ages 15 to 29 years) in an urban community were the subject of
      retrospective investigation through interviews with survivors and analyses of
      medical records. Classification in accordance with DSM-III-R showed a large
      proportion of axis II disorders. Borderline personality disorder (BPD) was found
      in 19 subjects (33%). When compared with subjects with other disorders, BPD
      subjects showed more antisocial traits and substance use disorders. Early
      parental absence, substance abuse in the homes, employment and financial
      problems, lack of a permanent residence, and sentence by court were also more
      frequent in BPD subjects.

PMID- 1997665
TI  - Impact of a humanmade disaster on the utilization pattern of a psychiatric
      emergency service.
AB  - In May 1980, Liberty City Miami, a black area, suffered a humanmade disaster: a
      riot. The effects of the riot on the utilization pattern of the only psychiatric
      emergency service (PES) for the Liberty City catchment area were studied in two
      ways: autocorrelation and cross-correlation analyses were used to determine
      whether PES presentations demonstrated a 7-day cycle and whether this cycle was
      disturbed by the riot; and analyses of variance (ANOVAs) were used to compare
      numerically the riot week to the preceding week, the riot week to the following
      12 weeks, and the 12 pre-riot weeks to the 12 post-riot weeks. Black PES
      presentations did not demonstrate a statistically discernable cycle, and none of
      the ANOVAs were statistically significant. It was concluded that the riot did not
      have a significant psychiatric morbidity effect as measured by PES presentation
      data. These results are discussed in reference to previous disaster studies.

PMID- 1997664
TI  - Self-ratings of anger and hostility in borderline personality disorder.
AB  - Forty-six patients with borderline personality disorder with and without major
      depression and 27 normal volunteers completed the Buss-Durkee Hostility
      Inventory, a self-rating scale of anger and hostility. The patients with
      borderline personality had significantly higher scores than the normal
      volunteers. The scores of the patients with borderline personality disorders were
      not related to gender, treatment or research setting, the degree of acute
      distress, or the presence of major depression. These findings suggest that a
      proneness to anger and hostility are enduring characteristics of borderline
      personality disorder and that anger and depression may represent independent
      clinical conditions with independent biological mechanisms regulating these two
      affective states.

PMID- 1997666
TI  - Demoralization and social supports among Holocaust survivors.
AB  - This study attempted to investigate the opposing effects of degree of
      traumatization and of contemporary social supports on the demoralization scores
      of World War II survivors. The respondents were all married, Poland-born
      respondents living in socially contrasting neighborhoods in Tel Aviv, Israel. Two
      subgroups were defined, one that had been in Europe during World War II (index
      cases) and another that was in prestatehood Israel during the same period
      (comparison cases). All respondents were administered the Psychiatric
      Epidemiology Research Interview/Demoralization Scale, a short item scale
      investigating World War II experiences, and the Social Supports Network
      Inventory. Uni- and multivariate analyses were conducted using means and rates of
      demoralization as the dependent variable. The results show that demoralization
      scores were associated positively with dose effect (the more brutal the
      experience, the higher the scores) and inversely with social supports (the higher
      the acknowledged presence of contemporary supports, the lower the scores).

PMID- 1997667
TI  - Lysergic acid diethylamide-induced chronic visual disturbances in an adolescent.

PMID- 1997668
TI  - Episodic alcoholism.

PMID- 1997669
TI  - Rosalyn Grennan: minister of health. Interview by Jim Buchheim.

PMID- 1997670
TI  - Alzheimer's: finding hope in despair.

PMID- 1997671
TI  - Daring to care.

PMID- 1997672
TI  - Battle between the Gods: the challenge of transcultural communication.

PMID- 1997673
TI  - Bells, bear hugs & mixed blessings: caring for an aging mother.

PMID- 1997674
TI  - Coccidia of Brazilian mammals: Eimeria marajoensis N. Sp. (Apicomplexa:
      Eimeriidae) from the Anteater, Tamandua tetradactyla (Xenarthra:
      Myrmecophagidae).
AB  - Feces from a juvenile specimen of the anteater Tamandua tetradactyla from Ponta
      de Pedras, Marajo, Para, northern Brazil, contained three different coccidial
      oocysts: Eimeria tamanduae Lainson, 1968; E. corticulata Lainson & Shaw, 1990;
      and a third species previously unrecorded and described here as Eimeria
      marajoensis n. sp. Oocysts of the latter parasite are spherical to subspherical,
      13.9 +/- 1.5 x 13.4 +/- 1.4 (11.1-16.5 x 11.1-16.5) microns, shape index
      (length/width) 1.0 (1.0-1.2). The oocyst wall is a single, colorless layer about
      0.6-1.0 microns thick with no striations or micropyle. There is no oocyst
      residuum, but a single, round, oval or irregularly shaped polar granule of about
      0.75-2.5 microns is consistently present. The sporocysts are broadly ellipsoidal,
      7.1 +/- 0.7 +/- 5.3 +/- 0.6 (6.0-8.8 x 4.0-5.7) microns, shape index 1.3 (1.2
      1.5), with a delicate wall bearing minute stieda body. No sub-stieda body was
      visible. The sporocyst residuum consists of some 10-20 rounded granules, lying
      between the two slightly curved sporozoites which measure approximately 6.5 x 2.0
      microns. Sporocyst refractile bodies were not discernable.

PMID- 1997675
TI  - Microfilum lutjani N. G. N. Sp. (Protozoa Microsporida), a gill parasite of the
      golden African snapper Lutjanus fulgens (Valenciennes, 1830) (Teleost
      Lutjanidae): developmental cycle and ultrastructure.
AB  - Microfilum lutjani n. g., n. sp. (Microsporida) was found on the gill filaments
      of Lutjanus fulgens (Teleost) inhabiting the coasts of Senegal. This
      microsporidium forms xenomas distinguished by the microvilli covering the plasma
      membrane. At all stages of development individuals have isolated nuclei and are
      in direct contact with the host cytoplasm. Merogony is binary and sporogony is
      tetrasporoblastic. The spore (4.75 x 2.60 microns) is characterized by a
      manubrium inserted on a laterally offset anchoring disc and extending into a very
      short, noncoiled polar filament (no longer than 500 nm) in the form of a hook.
      This type of polar filament has not been described previously in the
      Microsporida.

PMID- 1997676
TI  - In vitro development of exoerythrocytic forms of Plasmodium gallinaceum
      sporozoites in avian macrophages.
AB  - Exoerythrocytic forms of Plasmodium gallinaceum were cultured in vitro using
      salivary gland sporozoites extracted from experimentally infected Aedes
      fluviatilis mosquitoes. The host cells were macrophage precursors from chicken
      bone marrow. At various times after introduction of sporozoites, the cultures
      were stained by Giemsa or by immunofluorescence assay (IFA) using anti-sporozoite
      specific monoclonal antibodies (MAb). The time to complete parasite development
      in vitro was 50-70 h. By 70 h, ruptured segmenters and free merozoites were
      visible within the cells. Inoculation of normal chickens with infected cultures
      induced parasitemia after a pre-patent period of 10-11 days. In vitro young
      exoerythrocytic forms, late schizonts that include the matured segmenters, and
      free merozoites shared common antigens with the sporozoites as revealed by IFA
      using anti-sporozoite-specific MAbs. Our data indicate that macrophages support
      development of P. gallinaceum sporozoites and that the circumsporozoite proteins
      are present until the end of the primary exoerythrocytic schizogony.

PMID- 1997677
TI  - Effect of hyper-osmotic stress on alanine content of Leishmania major
      promastigotes.
AB  - Earlier studies showed that Leishmania major promastigotes are sensitive to
      osmotic conditions. A reduction in osmolality caused the cells to shorten and to
      rapidly release most of their large internal pool of alanine. In this study some
      effects of hyper-osmotic stress were examined. An increase in osmolality of the
      culture medium from 308 to 625 mOsm/kg caused only a small decrease in growth
      rate. When cells grown in the usual culture medium (308 mOsm/kg) were washed,
      resuspended in iso-osmotic buffer, and subjected to acute hyper-osmotic stress by
      addition of mannitol, the alanine content increased even in the absence of
      exogenous substrate. Promastigotes, depleted of alanine by a 5-min exposure to
      hypo-osmotic conditions, also synthesized alanine when resuspended in iso-osmotic
      buffer. Washed cells resuspended in iso-osmotic buffer consume their internal
      pool of alanine under aerobic conditions. Rates of consumption decreased on
      addition of mannitol, becoming zero at about 440 mOsm/kg. At higher osmolalities,
      alanine synthesis occurred. To estimate whether proteolysis could account for
      alanine synthesis in the absence of exogenous substrate, cells that had been
      grown with [1-14C]leucine were washed and resuspended under hypo-, iso-, and
      hyper-osmotic conditions and the amounts of 14CO2 and 14C-labelled peptides
      released in 1 h were measured. Little proteolysis occurred under these
      conditions, but the possibility that proteolysis was the source of the alanine
      increase, observed in response to hyper-osmotic stress, cannot be ruled out.

PMID- 1997678
TI  - Early development of Eimeria papillata (Apicomplexa: Eimeriidae) in the mouse.
AB  - Early development of Eimeria papillata (Apicomplexa) in the mouse was evaluated
      using Nomarski interference-contrast and brightfield microscopy. Sporozoite
      shaped meronts, which were motile and contained a large posterior refractile body
      and a smaller anterior refractile body, were observed entering and leaving host
      cells in the jejunum of an experimentally infected mouse at 26 h post inoculation
      (HPI). However, early developmental stages were not observed in tissue of the
      duodenum, ileum, cecum and colon. The mean length and width of these meronts (n =
      20) were 12.0 microns and 3.7 microns, respectively. Spherical or subspherical
      meronts containing crescent-shaped merozoites were observed at 36 HPI.

PMID- 1997679
TI  - Ultrasonographic posttreatment follow-up of breast cancer patients.
AB  - Clinical, radiographic (mammograms), and ultrasonographic data were compared
      retrospectively for 171 patients to evaluate the utility of ultrasound for the
      follow-up of breast cancer patients treated medically or by conservative surgery.
      When used to follow patients treated medically by induction or exclusive
      chemotherapy, ultrasonography accurately quantified tumor and nodal regression.
      After conservative surgery, sonograms are ideal to diagnose (and sometimes to
      treat) early complications such as hematoma, lymphocele, and abscess.
      Ultrasonography was more sensitive than mammography for the detection of late
      complications and benign lesions, but was insufficient for the detection of
      recurrent disease (95.5% sensitivity for radiography vs 90% for ultrasonography).
      After radical surgery and breast reconstruction, ultrasonography is the only
      procedure required for follow-up of patients with breast implants because it can
      determine the size and penetration of cutaneous recurrences. The fact that 30% of
      patients treated by lumpectomy and irradiation ultimately develop malignant or
      benign abnormalities justifies systematic ultrasonography for the follow-up of
      treated breast cancers. All sonographically demonstrable abnormalities warrant
      ultrasound-guided puncture biopsy.

PMID- 1997680
TI  - Can umbilical and arcuate artery Doppler velocimetry predict fetal distress among
      prolonged pregnancies?
AB  - We studied umbilical and arcuate artery Doppler velocity waveforms in 30
      uncompromised prolonged pregnancies (greater than 41 weeks of gestation). Normal
      systolic/diastolic ratios in these vessels had a negative predictive value
      similar to other antepartum tests. The positive predictive value, though, was not
      high enough to consider Doppler studies of the umbilical and arcuate arteries as
      the only test to identify the group of prolonged pregnancies that have
      uteroplacental insufficiency. There is a possibility that the combination of
      Doppler velocimetry with other antepartum tests may improve our ability to
      predict poor outcome. Further study is needed.

PMID- 1997681
TI  - Seminal vesicles. Imaging and intervention using transrectal ultrasound.
AB  - The seminal vesicles are difficult to evaluate clinically. Transrectal ultrasound
      (TRUS) has only recently allowed adequate assessment of these structures and
      their disorders. As the use of TRUS increases, radiologists must familiarize
      themselves with diseases of the seminal vesicles and the normal and abnormal
      appearance at ultrasound. This paper presents four cases illustrating the
      uncommon disorders that TRUS can demonstrate in the seminal vesicles: ectopic
      ureter entering the seminal vesicle, symmetrically enlarged seminal vesicles with
      male infertility, a pelvic arteriovenous malformation mimicking a seminal vesicle
      cyst, and tuberculosis. In two patients, TRUS was used to guide needle aspiration
      of seminal vesicle contents safely and to inject contrast for radiography.

PMID- 1997682
TI  - Carcinoma of ureterocele.

PMID- 1997684
TI  - Influence of fetal breathing and movements on variability of umbilical Doppler
      indices using different numbers of waveforms.
AB  - Umbilical artery continuous-wave Doppler ultrasound waveforms were obtained from
      three groups of fetuses in late gestation: during quiescence, fetal breathing
      movements, and fetal body movements. The coefficients of variation, calculated
      from three values for each Doppler index, which were derived from one, two, four,
      six and eight waveforms, decreased as the number of waveforms increased. However,
      statistical analysis showed no significant improvement in variance when more than
      four waveforms were used during fetal quiescence and breathing and when more than
      six waveforms were used during fetal movement. A minimum of six waveforms ensured
      coefficients of variation less than or equal to 10% even during fetal breathing
      and fetal movements.

PMID- 1997683
TI  - Frontal periventricular cysts on the first day of life. A one-year clinical
      follow-up and its significance.
AB  - During a 6-year period, the prospective interpretations of routine screening
      cranial ultrasound on 1453 premature infants indicated frontal periventricular
      cysts in 7 infants without other intracranial abnormalities during the first 24
      hours after birth. The medical records of these 7 infants and their mothers and a
      developmental assessment at age 1 year were also reviewed. The cysts were
      predominantly single and unilateral and ranged in size from 2 to 11 mm. One
      infant had bilateral subependymal cysts as well as frontal periventricular cysts.
      All 7 infants before 1 year of age demonstrated mild neurological deficiencies.
      However, 6 of 7 demonstrated partial or complete resolution of their neurological
      impairment by the end of 1 year. One infant was lost to clinical follow-up. The
      presence of these frontal periventricular cysts in the first 24 hours after birth
      suggests an in-utero event, such as antepartum hemorrhagic infarction, as their
      etiology.

PMID- 1997685
TI  - Sonographic features of fibromatosis of the breast.

PMID- 1997686
TI  - Nipple adenoma simulating carcinoma. Misleading clinical, mammographic,
      sonographic, and cytologic findings.

PMID- 1997687
TI  - Neonatal cystic testicular gonadoblastoma. Sonographic and pathologic findings.

PMID- 1997688
TI  - Comparison of endovaginal ultrasound and cytological evaluation of cystic ovarian
      tumors.
AB  - Endovaginal ultrasound is a good diagnostic tool for distinguishing between
      cystic and solid tumors. Unilocular cysts in the lower pelvis seem to carry a
      very low risk of malignancy in women of all ages. Cytological evaluation of the
      fluid from a cystic ovarian tumor has rather poor accuracy in diagnosing
      malignancy. For such a reason, this study compares the diagnostic accuracy of
      endovaginal ultrasound to that of cytology of the cyst content. Furthermore, we
      wanted to determine whether irrigation after puncture of a cystic tumor could
      increase the number of cells in the fluid and thereby increase the diagnostic
      accuracy of the cytological evaluation. Fifty women admitted to surgery due to a
      cystic tumor were endovaginally scanned the day before surgery. After the intact
      tumor had been removed from the abdomen, its contents were aspirated by means of
      a double-channelled needle. Irrigation was performed with Ringer acetate.
      Cytological evaluation was performed on both portions of the cyst fluid. The
      negative predictive value with respect to malignancy was 77% for cytology of the
      first portion of the aspirate, 81% for irrigation, and 100% for ultrasound. The
      corresponding figures for positive predictive value were 100%, 100%, and 73%. We
      conclude that cytological evaluation after irrigation of a cystic ovarian tumor
      does not significantly increase accuracy in diagnosing malignancy compared to
      endovaginal ultrasound.

PMID- 1997689
TI  - The role of adjuvant chemotherapy following cystectomy for invasive bladder
      cancer: a prospective comparative trial.
AB  - We assigned 91 patients with deeply invasive, pathological stage P3, P4 or N+ and
      Mo transitional cell carcinoma of the bladder (with or without squamous or
      glandular differentiation) to adjuvant chemotherapy or to observation after
      radical cystectomy and pelvic lymph node dissection. For most patients
      chemotherapy was planned as 4 courses at 28-day intervals of 100 mg./M.2
      cisplatin, 60 mg./M.2 doxorubicin and 600 mg./M.2 cyclophosphamide. A significant
      delay was shown in the time to progression (p = 0.0010) with 70% of the patients
      assigned to chemotherapy free of disease at 3 years compared to 46% in the
      observation group. Median survival time for patients in the chemotherapy group
      was 4.3 years compared to 2.4 years in the observation group (p = 0.0062). In
      addition to treatment groups, important prognostic factors included age, gender
      and lymph node status. The number of involved lymph nodes was the single most
      important variable. We recommend adjuvant chemotherapy for patients with invasive
      transitional cell carcinoma after definitive surgical resection.

PMID- 1997690
TI  - Spontaneous perinephric hemorrhage: imaging and management.
AB  - We report on 10 patients with spontaneous perinephric hemorrhage associated with
      underlying disease, including renal cell carcinoma (5), angiomyolipoma (2),
      malignant melanoma (1), periarteritis nodosa (1) and severe portal hypertension
      (1). The etiology could not be identified with computerized tomography (CT) in 5
      cases (50%), including 2 renal cell carcinomas, 1 angiomyolipoma, 1 periarteritis
      nodosa and 1 portal hypertension. Arteriography demonstrated underlying lesions
      in 4 of these 5 cases (80%) including the case of vasculitis. CT combined with
      magnetic resonance imaging is accurate for the diagnosis of spontaneous
      perinephric hemorrhage but the underlying pathological condition is often
      undetectable in the acute phase due to the perinephric blood. CT should be the
      first study performed if this diagnosis is suspected. Arteriography is
      recommended if a renal mass is not detected. If a mass is not identified with
      these 2 imaging studies and the patient is clinically stable, followup thin slice
      CT should be performed.

PMID- 1997691
TI  - Partial nephrectomy for renal cell carcinoma: indications, results and
      implications.
AB  - Of 52 patients who underwent partial nephrectomy for tumor 44 were found to have
      renal cell carcinoma. The indications for this parenchyma-sparing procedure were
      categorized according to the initial status of the contralateral kidney and
      included bilateral tumors or tumor in a solitary kidney in 16 patients (mandatory
      indications), unilateral carcinoma with compromise of the contralateral kidney by
      a benign disease process in 9 (relative indications) and small peripheral tumor
      with a normal contralateral kidney in 19 (elective indications). There were 4
      recurrences that accounted for 3 deaths, all in patients with mandatory
      indications. All patients who underwent partial nephrectomy for relative or
      elective indications were without definite evidence of recurrent disease at last
      followup (over-all mean 36 months). Our results suggest that conservative surgery
      can often provide effective and advantageous therapy for renal cancer and we
      encourage further consideration of the role of partial nephrectomy as an
      alternative to radical nephrectomy in selected patients with small peripheral
      tumors and normal contralateral kidneys.

PMID- 1997692
TI  - Percutaneous nephrolithotomy and the solitary kidney.
AB  - We reviewed 53 patients with stones in a solitary kidney who had undergone
      percutaneous nephrolithotomy. Previous surgery on that kidney had been performed
      in 35.8%, and 50.9% had other medical conditions including 26.4% who had impaired
      renal function. Staghorn or partial staghorn calculi were present in 52.9% and an
      additional 18.8% had multiple stones. Postoperative complications in 18.8% of the
      patients included sepsis, the need for transfusion and 1 death of
      bronchopneumonia. Percutaneous nephrolithotomy alone resulted in a 77.3% rate
      free of stone or fragments of 2 mm, or less. This rate increased to 86.8% with
      the addition of extracorporeal shock wave lithotripsy, ureteroscopy or open
      surgery (2 patients). Only 1 patient suffered long-term deterioration in renal
      function. Percutaneous nephrolithotomy is a safe procedure in the solitary
      kidney. It should be considered in those patients with complex stone burdens and
      impaired renal function when reduction in stone bulk and improved renal function
      may allow other treatment modalities to be used.

PMID- 1997693
TI  - Percutaneous nephrolithotomy for calculi in horseshoe kidneys.
AB  - Between 1983 and 1988, 15 patients (18 kidneys) underwent percutaneous
      nephrolithotomy at this unit for calculi in horseshoe kidneys. A standard 1-stage
      percutaneous access technique with minor modifications was used. In situ
      disintegration with ultrasound or electrohydraulic lithotripsy was necessary in
      15 moieties (83.3%) and nephrostomy drainage was required in 12 (66.7%).
      Percutaneous access was not a problem and there were minimal perioperative
      problems. Blood transfusion was required postoperatively in 2 patients. A total
      of 14 kidneys (77.8%) were rendered free of stone with percutaneous
      nephrolithotomy alone and 2 kidneys were left with asymptomatic stone fragments
      of 2 mm. or less. Another 2 kidneys became free of stone after extracorporeal
      shock wave lithotripsy, thus giving an over-all stone clearance rate of 88.8%. We
      conclude that percutaneous nephrolithotomy is an acceptable treatment for stones
      in horseshoe kidneys and it is the treatment of choice for patients in whom
      imaging is difficult or impossible.

PMID- 1997694
TI  - Extracorporeal shock wave lithotripsy of urinary calculi: experience in treatment
      of 3,278 patients using the Siemens Lithostar and Lithostar Plus.
AB  - Between March 1986 and June 1989, 3,278 patients with upper urinary tract calculi
      were treated at our medical center with the Lithostar lithotriptor. The stones
      were located in the calices in 41.9% of the cases, renal pelvis in 25.7% and
      ureter in 32.4%. Perirenal hematoma was noted in 0.5% of the patients but this
      resolved spontaneously within a few days. Auxiliary procedures were performed in
      37.3% of the cases, including Double-J stent and ureteral catheter in 26.8%,
      ureterorenoscopy in 2.1%, percutaneous nephrostomy in 1.6%, Zeiss loop in 4.3%
      and percutaneous nephrolithotripsy in 3.5%. Of the treatments 83.1% were
      performed without general or regional anesthesia. Followup after 3 months showed
      a 63.8% rate free of stone. The Lithostar upgraded with the overhead lithotripsy
      module is called Lithostar Plus. A total of 25 patients with upper urinary stones
      underwent treatment with the overhead module. Initial experience revealed
      fragmentation of stones after the first session in 20 patients, while a second
      session was necessary in 5. Analgesic sedation was used in 4 patients in whom a
      Double-J stent was inserted.

PMID- 1997695
TI  - Treatment of steinstrasse with repeat extracorporeal shock wave lithotripsy:
      experience with piezoelectric lithotriptor.
AB  - Among 958 patients with renal stones who underwent extracorporeal shock wave
      lithotripsy (ESWL) monotherapy using an EDAP-LT01 piezoelectric lithotriptor
      steinstrasse developed in 55 (5.7%). Of these 55 cases stone fragments passed
      spontaneously in 35 (63.6%) and were treated successfully (no residual stone
      fragment in ureter) with repeat ESWL in 18 (32.8%). Only 2 patients (3.6%)
      required ureteroscopic management or open ureterolithotomy. Therefore, repeat
      ESWL is considered a good initial method to treat complicated steinstrasse.

PMID- 1997696
TI  - A seromuscular stripping method to create a nipple valve without metal stapling
      for continent urinary reservoir.
AB  - Urinary continence with a Kock or Mainz pouch is achieved by a nipple valve of
      the invaginated ileum which is usually fixed with metal staples. However, metal
      staples can cause various complications as a foreign body. The seromuscular
      stripping method, a new technique to create a nipple valve, was applied to 17
      patients with bladder cancer in the construction of a continent urinary reservoir
      by the ileocolonic pouch (Mainz pouch). Metal staples were not used. The results
      were satisfactory except for 2 patients who became incontinent because of
      prolapse of the nipple in one and insufficient valve function due to ischemic
      change of the nipple valve in the other. Histology of the nipple valve from an
      autopsy case showed a good double layer nipple valve that functioned well to
      preserve continence.

PMID- 1997697
TI  - Sensitivity of urinary quantitative immunocytology with monoclonal antibody 486
      P3/12 in 241 unselected patients with bladder carcinoma.
AB  - We investigated the sensitivity of quantitative immunocytology with our
      monoclonal antibody 486 P3/12 in 241 unselected patients with transitional cell
      carcinoma. Immunocytology yielded a sensitivity of 91.8%, 89.4% and 92.9% for
      grade 1, 2 and 3 tumors, respectively. Standard cytology was positive in 59.2%,
      63.8% and 84.7%, respectively. Deoxyribonucleic acid flow cytometry, used in the
      first 69 patients, was positive in only 27.7%, 48.6% and 57.1%, respectively.

PMID- 1997698
TI  - Oral or intravesical bacillus Calmette-Guerin immunoprophylaxis in bladder
      carcinoma.
AB  - A total of 71 patients with superficial transitional cell carcinoma underwent
      transurethral resection of bladder tumor. All patients had stage pTa or pT1
      transitional cell carcinoma or carcinoma in situ without other concurrent
      malignancies. The patients were assigned to 3 treatment groups: control group-
      transurethral resection discontinued within the study, oral bacillus Calmette
      Guerin (BCG) group--transurethral resection of bladder tumor plus BCG (Moreau)
      and intravesical BCG group--transurethral resection of bladder tumor plus BCG. Of
      9 patients in the control group 8 (89%) experienced tumor recurrence during a
      mean followup of 20 months. Of the 28 patients in the oral BCG group 11 (39.3%)
      had recurrence during a mean followup of 36 months. Of the 34 patients in the
      intravesical group 6 (18%) had recurrence in a 24-month mean followup. The
      incidence of complications was higher in the intravesical (41.2%) than in the
      oral BCG group (28.5%). These results show that intravesical BCG is a more
      effective immunotherapy; however, oral BCG can be used in patients who do not
      accept intravesical BCG administration.

PMID- 1997699
TI  - Ileocolic neobladder post-cystectomy: continence and potency.
AB  - Incontinence and impotence are 2 of the primary complications associated with
      total bladder reconstruction after cystectomy for carcinoma. These and other
      features are addressed in 25 patients who underwent total neobladder
      reconstruction following cystectomy for transitional cell carcinoma. Of these
      patients 20 had a urethral anastomosis. No patient had to wear a pad or device.
      Enuresis was rare. When the radical cystoprostatectomy population was contrasted
      with a radical prostatectomy patient population, continence was achieved more
      rapidly in the neobladder group. Potency was maintained in 15 of 21 (71%)
      evaluable patients. This ileocolic neobladder produces a large volume and low
      pressure, and provides excellent day and night continence. With preservation of
      the neurovascular bundle potency can be maintained in the majority of patients.

PMID- 1997700
TI  - Results of 1,469 microsurgical vasectomy reversals by the Vasovasostomy Study
      Group.
AB  - During a 9-year period 1,469 men who underwent microsurgical vasectomy reversal
      procedures were studied at 5 institutions. Of 1,247 men who had first-time
      procedures sperm were present in the semen in 865 of 1,012 men (86%) who had
      postoperative semen analyses, and pregnancy occurred in 421 of 810 couples (52%)
      for whom information regarding conception was available. Rates of patency (return
      of sperm to the semen) and pregnancy varied depending on the interval from the
      vasectomy until its reversal. If the interval had been less than 3 years patency
      was 97% and pregnancy 76%, 3 to 8 years 88% and 53%, 9 to 14 years 79% and 44%
      and 15 years or more 71% and 30%. The patency and pregnancy rates were no better
      after 2-layer microsurgical vasovasostomy than after modified 1-layer
      microsurgical procedures and they were statistically the same for all patients
      regardless of the surgeon. When sperm were absent from the intraoperative vas
      fluid bilaterally and the patient underwent bilateral vasovasostomy rather than
      vasoepididymostomy, patency occurred in 50 of 83 patients (60%) and pregnancy in
      20 of 65 couples (31%). Neither presence nor absence of a sperm granuloma at the
      vasectomy site nor type of anesthesia affected results. Repeat microsurgical
      reversal procedures were less successful. A total of 222 repeat operations
      produced patency in 150 of 199 patients (75%) who had semen analyses and
      pregnancy was reported in 52 of 120 couples (43%).

PMID- 1997701
TI  - Impact of anatomical radical prostatectomy on urinary continence.
AB  - Urinary continence following an anatomical approach to radical prostatectomy was
      evaluated in 593 consecutive patients, 547 (92%) of whom achieved complete
      urinary control. Stress incontinence was present in 46 patients (8%), of whom 34
      (6%) wore 1 or fewer pads per day and 2 (0.3%) required placement of an
      artificial sphincter. No patient was totally incontinent. Age, weight of the
      prostate, prior transurethral resection of the prostate, pathological stage and
      preservation or wide excision of the neurovascular bundles had no significant
      influence on preservation of urinary control. These data suggest that anatomical
      factors rather than preservation of autonomic innervation may be responsible for
      the improved urinary control associated with an anatomical approach to radical
      prostatectomy.

PMID- 1997702
TI  - Primary orchiectomy versus estrogen therapy in advanced prostatic cancer--a
      randomized study: results after 7 to 10 years of followup.
AB  - Of 163 new consecutively diagnosed cases of advanced (T3-4 M0 or T04M1) prostatic
      cancer 13 had contraindications for estrogen treatment, and the remainder were
      randomized to orchiectomy (76) or to estrogen treatment (74), consisting of 150
      micrograms ethinyl estradiol daily and 80 mg. polyestradiol monthly. During the
      followup period of 7 to 10 years disease progression was noted in 27 patients
      (36%) treated with estrogen and 39 (51%) orchiectomized patients. The free of
      progression survival rate was significantly better (less than 0.05) among the
      estrogen treated patients but the over-all survival rates after orchiectomy and
      estrogen treatment were almost identical. A significantly higher frequency of
      cardiovascular side effects was noted in the estrogen group (23 cases) compared
      to the orchiectomy group (4 cases). Therefore, estrogen treatment in this form
      cannot be recommended for the palliative treatment of prostate cancer.

PMID- 1997703
TI  - Radical prostatectomy and adjuvant radioactive gold seed placement: results of
      treatment at 5 and 10 years for clinical stages A2, B1 and B2 cancer of the
      prostate.
AB  - Between 1977 and 1988, 131 patients with adenocarcinoma of the prostate underwent
      combined radical prostatectomy and intraoperative radioactive gold seed
      placement. Of these 131 patients 80 were clinically assessed as having stage A2
      (12), B1 (43) or B2 (25) cancer and they are the subject of this review. The
      average dose of radioactivity administered to each patient was 96.6 mCi, and mean
      followup was 65 months (median 64 months). No patient in this series received any
      other form of adjuvant therapy until disease recurrence was demonstrated. Local
      recurrences were observed in 2 patients (2.5%) in this series while distant
      recurrences were observed in 10 (12.5%). Cancer specific survival free of disease
      at 5 years was 100% for clinical stage A2, 91% for B1 and 75% for B2 cancers. The
      10-year survival free of disease was 100% for clinical stage A2, 82% for B1 and
      68% for B2 cancers. Covariants of clinical stage and seminal vesicle involvement
      influenced survival free of disease in a statistically significant manner (p less
      than 0.05) while pathological stage and degree of tumor differentiation did not.
      Mild to severe complications were observed in 12 patients (15%). Intraoperative
      placement of radioactive gold seeds into unresected pelvic tissues surrounding
      the site of prostatectomy offers a theoretical advantage in treatment by
      delivering tumoricidal levels of irradiation to residual foci of cancer not
      appreciated at the time of surgery. Our results suggest that increases in cancer
      specific survival free of disease over that previously reported for prostatectomy
      alone may be achieved through this combined treatment regimen. Furthermore, it is
      our opinion that therapeutic gains can be achieved without the attendant
      increases in morbidity and treatment delay often associated with adjuvant
      external beam radiotherapy.

PMID- 1997704
TI  - An objective score to predict upper tract deterioration in myelodysplasia.
AB  - Bladder dysfunction in myelodysplasia may present a significant hazard to the
      upper tract and a threat to kidney function. Urodynamic features of high leak
      pressure and detrusor-sphincter dyssynergia have been associated with an
      increased risk. We have developed an objective score to describe urodynamic
      findings in myelodysplasia. The score includes consideration of bladder
      compliance, detrusor contractility and reflux, in addition to leak pressure and
      sphincter behavior. In 171 myelodysplastic patients a significant correlation was
      demonstrated between the score and upper tract studies at the time of urodynamics
      and the score and the management decision. Of 73 myelodysplasia patients with
      normal upper tracts at the first urodynamics study hydronephrosis later developed
      in 14. The score was a potent predictor of outcome (p = 0.0006).

PMID- 1997705
TI  - Cystourethrometric findings in patients with detubularized right colonic segment
      for bladder replacement.
AB  - Urodynamic evaluation was performed in 13 men 4 to 18 months after
      cystoprostatectomy and bladder replacement using a detubularized right colonic
      segment. All patients are continent by day and only 3 are incontinent during the
      night to a degree that necessitates use of a condom catheter. Two patients awaken
      every 2 to 3 hours to void and the remainder have nocturia comparable to normal
      men of their age. The residual volume was 0 to 70 ml. The urethral closure
      pressure was normal, and in 3 patients studied preoperatively and postoperatively
      no significant change was observed other than shortening of the profile length.
      Maximal flow rates were normal although the pattern was intermittent. In 2
      patients no cystoplasty contractions were recorded and in all but 2 patients the
      amplitude of the contractions was less than 40 cm. water. Simultaneous bladder
      and urethral pressure recordings during bladder filling demonstrated no change in
      urethral pressure in 10 patients. Although creation of a reservoir with a low
      pressure and careful preservation of the infraprostatic urethra are important for
      continence in these patients, we believe that the absence of normal sacral route
      reflexes after cystoprostatectomy is an important contributing cause to nocturnal
      incontinence.

PMID- 1997706
TI  - Symptomatic splenic rupture following extracorporeal shock wave lithotripsy.

PMID- 1997707
TI  - Preoperative endoscopic diagnosis of fibroepithelial polyp of the renal pelvis: a
      case report and review of the literature.
AB  - Benign fibroepithelial polyps of the renal pelvis are rare, with only 9 cases
      described previously in the literature. We report an additional case and suggest
      how nephrectomy may be avoided.

PMID- 1997708
TI  - Nonspecific magnetic resonance appearance of renal oncocytomas: report of 3 cases
      and review of the literature.
AB  - We report the magnetic resonance appearance of 3 cases of solitary renal
      oncocytomas. All lesions were of low to moderate signal intensity on T1-weighted
      images and became considerably brighter on the more heavily T2-weighted images.
      One lesion contained a large central area of cystic degeneration, while the other
      2 were solid. A central stellate scar was present in the smaller of the 2 solid
      lesions. Our observations lend further support to earlier reports on the
      nonspecific magnetic resonance features of oncocytomas.

PMID- 1997709
TI  - Surgical management of renal cell carcinoma with extensive intracaval involvement
      using a venous bypass system suitable for rapid conversion to total
      cardiopulmonary bypass.
AB  - Renal cell carcinoma involves the vena cava in approximately 4% of the patients.
      Presently surgical extirpation is the only form of therapy that can result in
      cure. Recently management of extensive vena caval involvement has involved the
      use of cardiopulmonary bypass with circulatory arrest and hypothermia. We
      describe a technique using a venous bypass pump system (femoral vein to right
      atrium) for resection of renal cell carcinoma with suprahepatic vena caval
      extension (type II), which avoids the risks and complications of cardiac arrest
      and hypothermia but allows for rapid conversion to total cardiopulmonary bypass
      should the intraoperative need arise.

PMID- 1997711
TI  - Management of auto-emasculation in the psychotic state.
AB  - We report 2 cases of self-inflicted penile amputations, which offered differing
      surgical options and contrasting surgical results due to varying time delays. In
      1 case repair was done immediately, while repair in the other case was delayed by
      3 days due to the psychotic state of the patient. The psychiatric backgrounds of
      such episodes are discussed, as well as the techniques of repair and
      reconstruction.

PMID- 1997710
TI  - Spermatic cord for onlay coverage of urethral defect.
AB  - Segmental urethral necrosis may accompany scrotoperineal gangrene, and primary
      closure of the urethral defect may unacceptably reduce urethral dimensions. This
      dilemma has been managed successfully in 5 patients by application of the intact
      spermatic cord to the urethral defect and approximation to its margins. A
      representative case is described.

PMID- 1997712
TI  - Unbalanced chromosomal translocation associated with Sertoli-cell-only histology.

PMID- 1997713
TI  - Promoting urology research: whose job is it anyway?

PMID- 1997715
TI  - The National Kidney and Urologic Diseases Advisory Board 1990 long-range plan:
      Window on the 21st century.

PMID- 1997714
TI  - Long range plan of the National Kidney and Urologic Diseases Advisory Board.

PMID- 1997716
TI  - A continuous intravesical drug delivery system for the rat.
AB  - We describe a self-contained system for the continuous infusion of drugs into the
      rat urinary bladder. A reversible model of hydronephrosis is used to prepare one
      renal unit for nephrostomy tube placement. An 0.8 mm. silastic nephrostomy tube
      is introduced into the hydronephrotic kidney via a 16 gauge angiocath. The
      nephrostomy tube is then connected to an Alzet mini osmotic pump which is
      implanted in a subcutaneous location. The ability of this system to deliver a
      continuous dose of a test agent into the bladder was evaluated. Pumps were filled
      with a 1% solution of methylene blue in phosphate buffered saline. Following pump
      implantation, urinary samples were collected on a daily basis and subsequently
      analyzed for their concentration of methylene blue. At the completion of the
      experiment, specimens of the kidney, ureter, and bladder were histologically
      examined. Results demonstrated an average of 102% recovery of the theoretically
      delivered dose over a 14-day period. Renal histology demonstrated chronic
      inflammatory changes at the site of nephrostomy tube placement. No upper or lower
      tract urothelial changes were identified. This model provides a system for the
      continuous delivery of drugs in the rat urinary tract and results in no
      histological alteration to the lower urinary tract.

PMID- 1997717
TI  - Neuropeptide Y (NPY) in human penile corpus cavernosum tissue and circumflex
      veins--occurrence and in vitro effects.
AB  - The concentration and distribution of neuropeptide Y (NPY) within the penile
      corpus cavernosum (CC) and in penile circumflex veins (CV) from healthy potent
      males was investigated by immunochemistry and immunohistochemistry. The
      concentrations were assessed to 28.6 pmol/gm. (CC) and 15.8 pmol/gm. (CV)
      respectively. Gel filtration on CC tissue extracts demonstrated a single peak of
      NPY-immunoreactivity (NPY-IR) similar to synthetic human NPY. The NPY-IR was
      confined to nerve fibers seemingly innervating smooth muscle cells. In vitro
      myographic examinations demonstrated contractile activation by NPY in 2/8 CC
      strips and in 5/8 CV strips. The mean contractile force was 1.17 +/- 0.62 mN
      (18.3 +/- 15.8% of the K(+)-induced contraction) and 2.42 +/- 0.42 mN (31 +/-
      12%) respectively. NPY 10(-7) and 10(-6) M displayed a potentiating effect on the
      response to NA 10(-9) in one of six CC and four of six CV preparations. It is
      suggested that NPY could add to the contractile effect of NA in detumescence and
      in maintenance of the resting state; contribution of NPY to the veno-occlusive
      mechanism at initiation of erection is another putative physiological function.

PMID- 1997718
TI  - Determination of the coefficient of kinetic friction of urinary catheter
      materials.
AB  - The coefficient of kinetic friction plays an important role in the
      biocompatibility of urinary catheters. A method for determination of the in vivo
      coefficient of kinetic friction is described that allows the comparison of the
      catheter-urethral interaction of the various materials used in the production of
      urinary catheters and the different types of lubricants.

PMID- 1997719
TI  - Radio-contrast enhancement of urinary tract stones.
AB  - Most urologists treating stone disease with any method (ESWL, PCL, URS) have
      encountered problems of poor stone visualization with fluoroscopy. This
      difficulty to localize urinary tract (UT) stones or fragments may result in
      incomplete stone extraction, prolonged surgery and increased risk of recurrence
      and post-operative complications. We have sought and found means to increase the
      radioopacity of mineral UT stones by a simple pre-operative perfusion technique.
      The capacity of radioopacification has first been demonstrated in in vitro
      incubations of fragments of human mineral stones with aqueous solutions of
      barium, of the lanthanides and of the two natural actinides. Most of the
      incubations led to considerable radio-contrast enhancement and heavy metal
      incorporation, measured by X-ray fluorescence analysis. Dogs with implanted human
      stone fragments were used as an in vivo model. The UT were perfused through a
      retrograde pyelic catheter with heavy metal salts solutions, the ensuing
      radioopacification of the implanted UT-stones was estimated by abdominal
      radiographies and the metal incorporation was measured on the retrieved stones.
      Considerable radioopacity enhancement together with heavy metal incorporation was
      observed for the following elements: Sr, Ba and the lanthanides Gd and Yb. The
      pathological evaluation of the urothelial linings from animals treated with
      lanthanide salt showed no toxic effects.

PMID- 1997720
TI  - Assessment of the critical level of androgen for growth response of
      transplantable human prostatic carcinoma (PC-82) in nude mice.
AB  - The androgen dependent prostatic carcinoma of human origin, PC-82, was used as a
      model system to investigate the effect of various levels of androgen on the
      growth of prostatic tumor tissue. Plasma testosterone levels in mice were
      correlated to tumor growth and intratumor concentrations of testosterone and 5
      alpha-dihydrotestosterone. PC-82 tumor burden remained stable at plasma
      testosterone levels of 0.8 nmol/l., whereas tumor growth occurred at higher
      levels and tumor regression was observed at lower plasma levels. This critical
      level of testosterone corresponded with intratumor testosterone and 5 alpha
      dihydrotestosterone concentrations of six to 10 and three to four pmol/gm.
      tissue, respectively, which are significantly above the levels found in castrated
      non-supplemented animals (3.1 and 1.4 pmol/gm. respectively). This indicates that
      remaining concentrations of dihydrotestosterone, which amount to two to three
      times the castrate level, are not stimulatory for tumor growth in the model of
      the androgen dependent PC-82 tumor.

PMID- 1997722
TI  - Lumbosacral sympathetic trunk as a compensatory pathway for seminal emission
      after bilateral hypogastric nerve transections in the dog.
AB  - Seminal emission after transection of canine bilateral hypogastric nerves was
      investigated. Stimulation of severed hypogastric nerves caused full volume
      seminal emission (greater than four drops) in all six dogs examined. In contrast,
      stimulation of sympathetic trunks of other six dogs at the level of caudal
      mesenteric artery caused no emission in three dogs and a limited volume of
      seminal emission (less than one drop) by pressing the ampulla in the remaining.
      When hypogastric nerves were transected one month prior to the experiment,
      however, stimulation of sympathetic trunks in the same manner caused full volume
      of seminal emission in all six dogs. Distal dissection of sympathetic trunks
      demonstrated nerve fibers to the seminal tract via the pelvic splanchnic nerves.
      The results indicate that the seminal tract receives at least two sympathetic
      pathways; one from hypogastric nerves and the other from lumbosacral sympathetic
      trunks, and that the latter compensatorily generates seminal emission after
      hypogastric nerve transection.

PMID- 1997721
TI  - Chronic effects of focused electrohydraulic shock waves on renal function and
      hypertension.
AB  - The chronic effects of focused electrohydraulic shock waves were studied in a
      minipig model. Fifteen animals underwent a unilateral nephrectomy and
      compensatory renal hypertrophy was allowed to take place over a minimum of six
      months. Baseline studies were then carried out consisting of 1) serum creatinine,
      blood urea nitrogen, and plasma renin levels 2) intra-arterial blood pressure
      measurement and 3) 3H-inulin clearance. Ten of the animals then underwent 8
      shockwave treatments (2500 shocks per treatment), alternately to the upper and
      lower pole of the kidney, at two weeks intervals. A total of 20,000 shock waves
      were administered to each minipig over the four month period. The five control
      pigs underwent sham procedures. The renal function and blood pressure evaluations
      were then repeated. No significant decrease in renal function was noted in the
      experimental animals when compared to the controls. In addition, renin mediated
      hypertension was not observed despite the excessive number of total shock waves
      delivered to the kidney.

PMID- 1997723
TI  - Renal arterial duplex Doppler ultrasound in dogs with urinary obstruction.
AB  - Recent clinical studies using duplex Doppler sonography identified an alteration
      in renal arterial blood flow in obstructed hydronephrotic kidneys that reportedly
      can be used to distinguish obstructive from nonobstructive collecting system
      dilatation. We attempted to verify these clinical findings and establish the
      temporal relationship of the alteration in the Doppler spectrum to the onset of
      urinary obstruction by evaluating surgically induced urinary obstruction in dogs.
      We performed laparotomies on 11 dogs, with the left ureter isolated and ligated
      in five dogs, and left intact in six dogs (control group). Duplex Doppler
      examination of the left renal arteries performed nine times during the first
      postoperative month identified a statistically significant difference (p less
      than .05) in the Doppler resistive index calculation between the two groups on
      days 1, 2, 4, and week 4. A resistive index discriminatory threshold of 0.7
      (greater than 0.7, obstructed; less than 0.7, nonobstructed) produced a test
      sensitivity of 74% and specificity of 77%. We conclude from our study that renal
      arterial duplex Doppler sonography can detect a change in renal perfusion as a
      result of urinary obstruction and that this change can be detected as early as 24
      hours after obstruction. However, high false-positive and false-negative rates
      may limit the ability of this modality to reliably distinguish obstructive from
      nonobstructive collecting system dilatation.

PMID- 1997724
TI  - Experimental intravesical therapy for superficial transitional cell carcinoma in
      a rat bladder tumor model.
AB  - A rodent bladder cancer model that is induced by intravesical instillation of N
      methyl-N-nitrosourea (MNU) was characterized. Cohorts of four to five week old
      female Fisher 344 rats received four biweekly 1.5 mg. doses of intravesical MNU
      and were sacrificed at various intervals. By week 13 all animals had flat atypia
      and/or papillary transitional cell tumors, and 67% of the lesions were moderately
      (grade II) or poorly differentiated (grade III). By week 20, 83% had gross muscle
      invasive tumors that eventually killed the host. A cohort of 40 MNU treated
      animals was subsequently treated commencing at week 17 after initiation of MNU
      with one of three intravesical six week regimens: 1) saline; 2) BCG (Tice
      strain); or 3) recombinant human tumor necrosis factor (RTNF) plus adriamycin.
      There was no difference in animal survival or tumor growth in any group of
      animals commencing therapy at week 17. A second cohort of 107 animals commenced
      therapy at 13 weeks after initiation of MNU with one of five intravesical six
      week regimens: 1) intravesical BCG (Tice strain); 2) adriamycin; 3) recombinant
      human tumor necrosis factor (RTNF); 4) RTNF plus adriamycin; or 5) BCG plus
      adriamycin. BCG, RTNF or adriamycin alone had no effect on tumor growth; however,
      BCG plus adriamycin and RTNF plus adriamycin commencing at week 13 significantly
      inhibited tumor growth and progression. In conclusion, this autochthonous
      intravesical rodent transitional cell carcinoma model appears useful for the
      following reasons: 1) it closely resembles human transitional cell carcinoma
      histologically and biologically in that all animals develop neoplastic changes in
      situ that progress to muscle invasion and kill the host; 2) as with human bladder
      cancer these tumors do not respond to intravesical therapy if treated when tumor
      burden is large; however, tumor growth is inhibited when treated early; and 3)
      this model appears appropriate for screening and developing new intravesical
      treatments for superficial bladder cancer.

PMID- 1997725
TI  - The effect of radiation therapy and hyperthermia on a human prostatic carcinoma
      cell line grown in athymic nude mice.
AB  - The effect of radiation and/or hyperthermia on a human prostatic carcinoma
      xenograft in athymic nude mice was investigated. A human prostate carcinoma
      subline (1-LN-PC-3-1A) was inoculated subcutaneously in the thigh of male athymic
      nude mice. When tumors reached a size of approximately 200 mm.3, they were
      treated with either radiation (X) or hyperthermia (H) alone, or in combination (X
      + H). In the combined treatment, hyperthermia was delivered immediately after
      radiation exposure. Comparison of the time required to reach twice the tumor
      volume observed at the time of treatment was used to define therapeutic impact on
      tumor growth. The combined treatment resulted in median tumor volume doubling
      time of 35.5 days, compared to 18 days and 25.5 days, respectively, for
      hyperthermia or radiation alone. Analysis of tumor doubling time using a
      proportional hazards regression indicates that under the conditions of this
      experiment, the effect of radiation and hyperthermia for 1-LN-PC-3-1A tumors is
      additive. The impact of this treatment regimen in the management of prostatic
      cancer requires further investigation.

PMID- 1997726
TI  - Image guided localized 31P magnetic resonance spectroscopy of acute urinary tract
      obstruction.
AB  - Using 31P magnetic resonance spectroscopy, localized spectroscopy and magnetic
      resonance imaging we studied effects of acute urinary obstruction in the in vivo
      pig kidney. Accumulation of urine in the renal pelvis and collecting ducts
      resulted in the appearance of a new peak in the localized phosphorus spectra
      originating in the renal papilla, resonating at 3.43 to 4.56 ppm. This was
      inorganic phosphate with a pH of 5.60 to 6.79 (urine pH). Imaging did not show
      any dilatation of renal pelvis. There was a significant time dependent fall in
      renal [ATP] during urinary obstruction followed by a rapid "overshoot" of [ATP]
      and disappearance of the phosphate peak after release of obstruction. Possible
      mechanisms for this phenomenon are discussed. We conclude that 31P magnetic
      resonance spectroscopy provides early evidence of urinary obstruction in vivo and
      could be of value in clinical diagnosis.

PMID- 1997727
TI  - The effects of interleukin-6 on tumor-infiltrating lymphocytes derived from human
      renal cell cancer.
AB  - Tumor-infiltrating lymphocytes (TIL) are a heterogeneous population of T cells
      with potent antitumor activity against a wide variety of tumors. TIL from renal
      cell cancer (RCC) typically exhibit diminished growth and antitumor activity
      after four weeks in vitro. We have therefore investigated effects of varying
      doses of interleukin-6 (IL-6) (0, 25, 100 units/ml.) on in vitro expansion,
      proliferation, cytotoxicity, and expression of cell surface phenotypes of long
      term renal TIL cultures from three RCC patients. Among the various conditions
      tested, three of three TIL cultures displayed a mild increase in cell expansion
      when grown in IL-2 with the addition of 100 units/ml. of IL-6. Two of three TIL
      cultures grown in IL-2 and 100 U/ml. of IL-6 demonstrated enhanced proliferation
      as determined by 3H-thymidine uptake. TIL could not be isolated or maintained in
      vitro when grown in the presence of IL-6 alone without IL-2. IL-6 was also found
      to enhance the long term non-specific cytotoxicity against an allogeneic nonrenal
      tumor target. No consistent effect on autologous tumor-specific cytotoxicity was
      demonstrated. We conclude that IL-6, when used in combination with IL-2, may
      modestly enhance the long-term growth of RCC-derived TIL.

PMID- 1997728
TI  - From regeneration to scar formation: the collagen way.

PMID- 1997729
TI  - Microglia in human disease, with an emphasis on acquired immune deficiency
      syndrome.
AB  - In conclusion, there is overwhelming evidence that within the CNS the primary
      sites of active HIV-1 infection are microglia. CNS infection may be related to
      the normal repopulation of the CNS by monocytes (microglial turnover) that carry
      latent infection into the CNS. Activation of viral infection may depend upon
      microglial differentiation, soluble factors (cytokines), and/or coexistent
      infections. Infection of microglia may disturb the normal hemostatic balance that
      exists between microglia and other glia, and between microglia and neurons,
      processes that are only recently being explored at the molecular level. The
      impact that HIV infection of microglia may have on synaptic integrity is unknown.
      Cytokines appear to be prime candidates as mediators of some of the adverse
      effects of microglial infection on other CNS cells, myelin and endothelial cells.

PMID- 1997730
TI  - The extracellular matrix in hepatic regeneration. Localization of collagen types
      I, III, IV, laminin, and fibronectin.
AB  - After partial hepatectomy, the liver is capable of complete regeneration,
      restoring normal hepatic size, architecture, and function. To study the role of
      the extracellular matrix in regeneration, the temporal and spatial sequence of
      deposition of several of its components, including collagen types I, III, and IV,
      laminin, and fibronectin, in rat liver, after an 80% hepatectomy, was
      characterized by light microscopy immunohistochemistry. A minimum of five animals
      were studied for each date. In agreement with previous reports, subsequent to 80%
      hepatectomy, there was a brisk mitosis of hepatocytes. The mitotic activity was
      maximal at 48 hours, primarily in the periportal and centrilobular zones, and
      resulted in the formation of hepatocyte clusters and widening of the hepatic
      plates. Of the extracellular matrix components studied, laminin was the one
      demonstrating the most dramatic changes. By 24 hours, laminin appeared in the
      hepatic sinusoids reaching a maximum staining intensity at 48 hours.
      Intracellular laminin was prominent in numerous non-parenchymal cells, with many
      having the morphology, location, and desmin content characteristic of Ito cells.
      Laminin staining decreased in the sinusoids at 4 days; however, some
      intracellular staining of Ito cells was present even at 8 days after hepatectomy.
      At the completion of regeneration, there was no evidence of any substantial
      change in the ratio: extracellular matrix/cell mass. The results indicate that:
      (a) hepatocytes can divide without prior removal of the subsinusoidal
      extracellular matrix; (b) during regeneration, hepatocyte division precedes
      sinusoidal formation; (c) during hepatic regeneration, and in spite of the
      presence of laminin in Ito cells, no basement membranes are formed; (d) the
      prominent expression of laminin and its proposed functions in morphogenesis
      suggest a critical role for this matrix component in the formation and
      reorganization of the regenerating liver.

PMID- 1997731
TI  - Intralobular heterogeneity of carbon tetrachloride-induced oxidative stress in
      perfused rat liver visualized by digital imaging fluorescence microscopy.
AB  - Spatial and temporal alterations in carbon tetrachloride-induced oxidative stress
      were studied in perfused hepatic microcirculatory units of the rat by digital
      imaging microscopic fluorography using dichlorofluorescin diacetate, a
      hydroperoxide-sensitive fluorogenic probe. The surface of the liver loaded with
      dichlorofluorescin was microscopically visualized, and the fluorescence of
      dichlorofluorescin (DCF), a highly fluorescent molecule generated by
      hydroperoxide-mediated oxidation of dichlorofluorescin, was digitally processed.
      After completing the experiments, fluorescein-labeled albumin was injected into
      the perfusate to confirm the state of sinusoidal perfusion and the topography of
      hepatic microangioarchitecture in the area studied. During transportal infusion
      of carbon tetrachloride, DCF fluorescence was observed predominantly in the
      pericentral area and was attenuated by pretreatment with SKF-525A, suggesting the
      involvement of cytochrome P-450. After peaking at the maximum level, the
      pericentral DCF fluorescence gradually decreased in parallel to the loss of
      viability, implicating the causal role of intracellular hydroperoxide formation
      in hepatocellular injury. In retrogradely perfused liver, in which intralobular
      O2 gradient was reversed, no significant activation of DCF fluorescence was
      observed among hepatic lobules. It is therefore conceivable that the zonal
      heterogeneity of carbon tetrachloride-induced lipid peroxidation may depend on at
      least two factors, sinusoidal oxygenation and the intralobular distribution of
      cytochrome P-450. Furthermore, development of the current technique will provide
      a useful method to investigate the microtopography of oxidative stress in organ
      microcirculatory units.

PMID- 1997732
TI  - Developmentally regulated changes in extracellular matrix in endothelial and
      smooth muscle cells in the ductus arteriosus may be related to intimal
      proliferation.
AB  - In the late gestation fetal lamb ductus arteriosus (DA), intimal proliferation is
      observed, characterized by smooth muscle migration and proliferation in the
      subendothelium. The nature of changes in the endothelial and smooth muscle
      extracellular matrix associated with the development of this feature are not
      known. We assessed the production of glycoproteins (fibronectin, laminin, and
      type IV collagen) and glycosaminoglycans (GAGs) (hyaluronic acid, heparan
      sulfate, and chondroitin sulfate) in endothelial and smooth muscle cells
      harvested from the DA, aorta (Ao), and pulmonary artery of fetal lambs at 100
      days gestation, before the appearance of DA intimal proliferation, and at 138
      days, when well-developed intimal 'cushions' are seen. In passage 3 cells,
      glycoprotein synthesis was measured by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis after 48 hours incubation with [35S]methionine, and GAGs were
      assessed by labeling with [3H] glucosamine and separation on DEAE ion-exchange
      high performance liquid chromatography. Analyses were carried out on culture
      medium, cell layer, and solubilized matrix. Fibronectin secretion by DA smooth
      muscle cells from 100-day lambs was found to be twice that of Ao or pulmonary
      artery cells. No significant differences were seen in smooth muscle cells from
      138-day lambs or when comparing endothelial cells from each of the vascular sites
      at both gestational ages. As well, there were no DA-specific differences in
      laminin or type IV collagen. No significant differences in endothelial GAG
      secretion were observed comparing each vascular site at both gestational ages.
      Analysis of endothelial-derived matrices, however, revealed increased
      incorporation of hyaluronic acid in the DA from 100-day lambs, 10-fold that of
      the pulmonary artery and Ao, and increased heparan sulfate. These differences
      were still present in cell matrices from late gestation animals, but were less
      marked. No differences in GAGs were seen when comparing smooth muscle cells.
      Incubation of 100-day DA and Ao smooth muscle cells with endothelial conditioned
      medium however, resulted in a 2-fold increase in chondroitin sulfate in DA,
      compared with Ao. These results indicate that distinct, developmentally regulated
      patterns of extracellular matrix production are related to vascular site and
      specific features appear to precede intimal proliferation in the DA.

PMID- 1997733
TI  - Carcinogen-induced alterations in rat liver DNA adduct formation determined by
      computerized fluorescent image analysis.
AB  - These studies employed continuous feeding of a carcinogenic level of N-2
      acetylaminofluorene to male rats for 28 days. Under these conditions normal
      hepatocytes are known to be inhibited from proliferation, whereas xenobiotic
      resistant putative preneoplastic hepatocytes with altered liver enzyme phenotypic
      expression appear to have a growth advantage. A novel technique using
      computerized fluorescent image analysis of triple-stained frozen liver sections
      was developed and used to visualize three different molecular markers in
      individual hepatic cells. Proliferating liver cells were identified by anti-5
      bromodeoxyuridine immunostaining in livers of rats injected with 5
      bromodeoxyuridine 1 hour before sacrifice. Anti-cytokeratin immunostaining was
      used to identify bile ducts and putative oval cells. Characterization of DNA
      adduct formation was achieved with an antiserum specific for N-(deoxyguanosine-8
      yl)-2-aminofluorene, the major DNA adduct of 2-acetylaminofluorene. The image
      analysis demonstrated low but distinct DNA adduct concentrations in putative oval
      cells identified by anti-cytokeratin staining and in scattered, replicating liver
      cells recognized by anti-5-bromodeoxyuridine. Adducts were not detected in
      replicating foci consisting of 3 to 11 nuclei. It is possible that proliferating
      liver cells that have low N-2-acetylaminofluorene-DNA adduct levels may clonally
      expand to become foci protected from further adduct accumulation and
      preneoplastic liver lesions. Thus, the computerized fluorescent image analysis
      demonstrated here may provide a novel procedure for identification of carcinogen
      induced liver cell alterations.

PMID- 1997734
TI  - The dynamics of intestinal eosinophil depletion in rats treated with
      dexamethasone.
AB  - We examined the effects of corticosteroid treatment on eosinophils in the jejunal
      mucosa of rats previously infected with Nippostrongylus brasiliensis. Rats
      received a single intraperitoneal injection of 1 mg of dexamethasone. At a light
      microscopic level, the number of eosinophils with typical nuclei and granules was
      significantly decreased as early as 3 hours after injection, and had diminished
      to 17% of starting values at 24 hours. Pyknotic cells containing eosinophilic
      granules or fragments were observed scattered in the subepithelial interstitial
      space 3 and 7 hours after injection. By electron microscopy, more than 20% of
      eosinophils demonstrated nuclear abnormalities. Degenerating eosinophils without
      granular changes (27 of 127, 14.1%) or with or with granular changes (9 of 127,
      7.1%) increased at 3 hours compared with untreated rats (8 of 233, 3.4%; 4 of
      233, 1.7%). At 7 hours, 47 of 96 (49.0%) eosinophils were located inside
      phagocytic vacuoles of macrophages. Single macrophages occasionally engulfed two
      or more eosinophils. Only a few degeneration eosinophils (7 of 96) were observed
      outside macrophages. At 13 hours, the percentage of degenerating eosinophils and
      eosinophils inside macrophages was decreased; at 24 hours, few eosinophils were
      seen and eosinophil structures could not be identified inside macrophages. The
      epithelium and lamina propria did not show structural damage typical of an
      inflammatory reaction at any time. Eosinophil numbers in mesenteric lymph nodes,
      spleens, and peripheral blood were also reduced by dexamethasone. Similar
      observations were made in the jejunal mucosa of noninfected rats. We observed the
      slow restoration of eosinophil numbers in the intestinal wall, finally reaching
      preinjection numbers after 14 days. We conclude that dexamethasone has important
      effects on eosinophils causing (a) nuclear degeneration and (b) changes in the
      granular matrix. Subsequently, these damaged eosinophils are engulfed by
      macrophages and swiftly disappear from the intestinal mucosa. These effects
      appear to be due to the induction of apoptosis. Our findings offer an explanation
      for one of the significant antiinflammatory effects observed with the use of
      corticosteroids.

PMID- 1997735
TI  - Macrophage uptake of low-density lipoprotein modified by 4-hydroxynonenal. An
      ultrastructural study.
AB  - We have documented the ultrastructural characteristics of the uptake and
      processing by mouse peritoneal macrophages (MPM) of low-density lipoprotein (LDL)
      modified with 4-hydroxynonenal (HNE), an intermediate of lipid peroxidation. This
      was performed as part of a larger biochemical study assessing the role of LDL
      oxidation in lipid loading of macrophages during atherogenesis. Gold-labeled LDL
      that was modified with HNE leading to particle aggregation represented the
      morphologic probe used. When incubated with MPM, the probe became associated with
      short segments of cell membrane, probably derived from blebs or from lysed cells.
      At 37 degrees C there was a time-dependent increase in uptake by MPM, and at 4
      hours the increase paralleled the degradation by MPM of 125I-labeled HNE-LDL-cAu.
      Clathrin-coated pits on the cell surface were consistently associated with probe.
      Uptake of probe appeared to occur via phagocytosis, because pseudopods frequently
      surrounded probe, and cytochalasin D quantitatively prevented probe uptake. A
      time-dependent increase was found in the number of gold particles per unit area
      within vacuoles, some of which were secondary lysosomes, based on acid
      phosphatase-positive staining. Thus, HNE-induced aggregation of LDL during
      oxidation, binding of aggregates to clathrin-coated pits on MPM, and subsequent
      phagocytosis may represent one of the ways lipid-laden foam cells are formed in
      vivo.

PMID- 1997736
TI  - Amyloid fibril formation in the rough endoplasmic reticulum of plasma cells from
      a patient with localized A lambda amyloidosis.
AB  - Evidence for amyloid fibril formation in rough endoplasmic reticulum (RER) of
      plasma cells from the duodenum of a 62-year-old man with localized A lambda
      amyloidosis is described. The inclusions in RER of plasma cells were composed of
      tightly packed, regular arrays of fibrils cut in both longitudinal and cross
      sections. The fibrils within the inclusions, measuring 10 nm in width, were
      oriented parallel to the long axis of the inclusions. By immunoelectron
      microscopy with an antihuman A lambda antiserum, gold particles labeled the
      fibrils located both in the RER of plasma cells and in the extracellular space.
      In addition, electron-dense material in the dilated RER was occasionally labeled.
      These findings suggest that at least some amyloid fibrils are unequivocally
      created in the RER of plasma cells.

PMID- 1997738
TI  - Constitution and Bylaws. Tennessee Dental Association, 1990.

PMID- 1997739
TI  - Infectious waste regulations and how they affect the individual health care
      practitioner--the REAL Story.

PMID- 1997737
TI  - Morphology of menstrual hemostasis in essential menorrhagia.
AB  - We performed a morphologic and morphometric study with light and electron
      microscopy on early menstrual hemostasis in five menorrhagic uteri and one
      control uterus, related the data to measured menstrual blood loss and compared
      the data with our previous study on normal menstruation. Menstrual blood loss
      ranged from 39 to 234 ml. Menorrhagic uteri contained large hemostatic plugs,
      protruding with a large part into the extravascular space. These plugs often
      consisted of loosely packed, poorly degranulated platelets with few fibrin
      fibers. Recanalized plugs, consisting of fibrin fibers and platelet remnants at
      the periphery of the vessel, were also observed in menorrhagic uteri. Using
      morphometry, we demonstrated a positive correlation between menstrual blood loss
      and the number of occlusive and nonocclusive hemostatic plugs, but not with other
      aspects of hemostatic plug formation such as the vessel area occluded by the
      plug, plug transformation, or intra- or extravascular localization of the plug.
      Vasodilation or endometrial height were not correlated with the amount of
      menstrual blood loss. These data suggest that essential menorrhagia is associated
      with fragile hemostatic plugs or with more extensive vessel damage.

PMID- 1997740
TI  - Talon cusp: a review with three cases from native North America.
AB  - Supernumerary lingual tubercles ("talon cusps") in three North American Indians
      are reported. These cusp-like structures typically occur unilaterally on
      permanent maxillary lateral incisors. We speculate that sporadic occurrences of
      this type probably are induced by trauma or other localized insults affecting the
      tooth germ. Multiple occurrences in an individual may have a separate etiology,
      the most severely affected cases being associated with craniofacial syndromes.

PMID- 1997741
TI  - Relationship between clonality and transformation in acute leukemia.
AB  - In some cases of acute leukemia an initial potentially leukemogenic genetic
      alteration can result in clonally derived end-cells normal in appearance and
      numbers. We refer to this clonal expansion as preleukemia. Subsequent
      alterations, intrinsic or extrinsic, often referred to as transformation, result
      in abnormal differentiation and/or growth regulation; we refer to this as
      leukemia. Several issues are unresolved. Where in the hierarchy of hematopoiesis
      clonal expansion and transformation occur is unknown. It is quite likely that
      clonal expansion occurs in cells with considerable self-renewal potential-
      probably stem or progenitor cells. The precise site may vary in different cases
      and account for the diverse phenotypes of acute leukemia. How the preleukemia
      clone comes to dominate hematopoiesis and the fate of the residual normal stem
      cells and their progeny are also unknown. Likewise, there is controversy whether
      different models of leukemogenesis operate in different subjects. For example,
      are older persons or those with occupational exposure to potentially leukomogenic
      agents more likely to exhibit one pattern of leukomogenesis? Finally, it is
      unknown whether these diverse models of leukemogenesis respond differently to
      therapy.

PMID- 1997742
TI  - Doxorubicin and m-AMSA induced DNA damage in blast cells from AML patients.
AB  - We investigated m-AMSA or doxorubicin (Dx) induced DNA single-strand breaks (DNA
      SSB) in myeloid leukemia cells obtained from 8 adult patients suffering from AML.
      Highly purified AML cells were stimulated to proliferate with the addition of the
      appropriate growth factor (GCT) and exposed to different concentrations of m-AMSA
      or Dx for 1 or 4 h, respectively. DNA-SSB were determined by alkaline elution
      techniques. Either the kinetics or the amounts of DNA-SSB caused by both
      topoisomerase II inhibitors were variable among different cases. By increasing m
      AMSA concentrations there was a concomitant increase in DNA-SSB up to a plateau
      at the highest concentrations. Dx induced DNA-SSB followed a bell shape curve
      with a decrease in the number of breaks at the highest concentrations that was
      evident in most cases. The interindividual variability of Dx-induced DNA-SSB was
      not correlated with intracellular Dx concentrations as assessed by flow
      cytometry. No correlation was evident between the amount of DNA breaks induced by
      m-AMSA and that induced by Dx. These data suggest that AML cells derived from
      different patients are not necessarily cross-sensitive or cross-resistant to
      topoisomerase II inhibitors with different chemical structures such as amsacrine
      or anthracyclines.

PMID- 1997743
TI  - Experimental treatment of L-801 myeloid leukemia mice with low molecular weight
      natural tumor suppressor of human fetal brain origin.
AB  - In human fetal brain tissue there is a low molecular weight suppressor substance
      which can preferentially suppress murine myeloid leukemic cell (L-801) growth,
      but with less harmful effects on the growth of normal bone marrow hemopoietic
      stem cells (CFU-S) and granuloid/macrophage progenitors (CFU-GM) in vitro liquid
      or agar culture. Mice after inoculation of L-801 cells died within 10-17 days due
      to development of leukemia. After consecutive injections of the low molecular
      weight suppressor substance isolated from human fetal brain tissue some of the
      leukemic mice survived. No pathological changes were observed in the mice which
      survived longer than 100 days after inoculation of L-801 cells.

PMID- 1997744
TI  - Reversible leukaemic regrowth under GM-CSF treatment after chemotherapy for AML.
AB  - A 78-year-old woman with acute myelogenic leukaemia (AML M5 (FAB)) was treated
      with standard induction chemotherapy followed by recombinant human granulocyte
      macrophage colony-stimulating factor (rhGM-CSF) (250 micrograms/m2/day) in an
      effort to accelerate neutrophil recovery. After 10 days of rhGM-CSF therapy,
      increasing numbers of promonocytes and monocytes were detected in the peripheral
      blood, with a maximum total white blood count of 14,900/microliters of which 39%
      were promonocytes, 39% monocytes, and only 3% neutrophils. The bone marrow during
      GM-CSF therapy was hypercellular and contained 95% monocytic forms. After
      discontinuation of rhGM-CSF, this monocyte lineage stimulation was completely
      reversible. Without further chemotherapy the patient entered a complete remission
      after 9 months and is now relapse free after 24 months. Since the stimulation was
      restricted to the previously leukaemic lineage of this patient, the profound
      monocytosis observed in this case suggests the possibility that GM-CSF may exert
      reversible effects on the proliferation of clonogenic cells in acute monocytic
      leukaemia.

PMID- 1997745
TI  - ABL oncogene expression during erythroleukemia cell differentiation.
AB  - The translocation between chromosome 9 and chromosome 22 which creates the
      Philadelphia chromosome moves the ABL oncogene from its normal location on
      chromosome 9 and fuses it with a portion of the BCR gene on chromosome 22. This
      new BCR/ABL fusion gene generates a unique 8.7 kilobase (kb) RNA which codes for
      a new 210 kilodalton (kd, p210) protein which has a protein tyrosine kinase
      activity that is greatly increased in comparison to the normal ABL protein. The
      human K562 cell line was derived from a patient with CML, and serves as one model
      for the regulation of expression of the ABL and BCR/ABL genes. This study
      examines the expression of the BCR/ABL fusion gene and the normal ABL gene in
      relation to differentiation and changes in proliferative state. The expression of
      both the normal ABL transcripts and the BCR/ABL fusion transcript decrease
      approximately ten-fold when the cells are induced to differentiate with hemin. In
      contrast, expression of the MYC oncogene is unaffected by hemin-induced
      differentiation. The results suggest that both ABL and BCR/ABL expression vary in
      proportion to the differentiation of the cells, but minimally if at all as a
      function of the cells' proliferative state.

PMID- 1997746
TI  - Detection of single-stranded DNA damage using monoclonal anti-thymidine antibody.
AB  - A method to detect single-stranded DNA damage from individual cells has been
      developed using a monoclonal anti-thymidine antibody (MoAb20B7). Initially, HL-60
      cells were incubated with daunomycin at different concentrations, and processed
      by MoAb20B7. While 73.5% of the cells incubated with 5 micrograms/ml of
      daunomycin for 24 h reacted positively with MoAb20B7, 83.5% cells at 10
      micrograms/ml daunomycin dose were positive. Next, this method was combined with
      unscheduled DNA synthesis to simultaneously measure repair and damage from
      individual cells. Finally, patients with acute myeloid leukemias were studied
      before and 24 h after therapy with a daunomycin containing regimen. In vivo
      damage could be determined in a prompt fashion.

PMID- 1997747
TI  - For the health of it. Pain in the neck: Part II.

PMID- 1997748
TI  - The nursing shortage: problem or challenge?

PMID- 1997749
TI  - The Computerized Psychiatric Severity Index as a predictor of inpatient length of
      stay for psychoses.
AB  - The Computerized Psychiatric Severity Index (CPSI), developed by Susan D. Horn
      and colleagues at The Johns Hopkins University School of Hygiene and Public
      Health, was used to study the severity of mental illness of 304 patients with
      discharge diagnosis of schizophrenia or affective disorder, and no secondary
      psychiatric diagnoses (DRG 430). The CPSI explained 13.7% of the variation in
      length of stay for these patients (14.31% of the variation in length of stay for
      affective disorders and 10.04% for the schizophrenia). Length of stay was an
      appropriate measure of the dependent variable resource use since it correlated
      0.96 with total charges.

PMID- 1997751
TI  - Health care utilization and functional status in the aged following a fall.
AB  - Falls in the aged may lead to increases in health care utilization and declines
      in functional status. The Longitudinal Study of Aging was analyzed to test the
      hypotheses that use of the health care system is greater in elderly persons
      subsequent to a fall in the preceding year than in those who have not fallen and
      that fallers are more likely to decline in function than are nonfallers. One-time
      fallers and, especially repeated fallers, (2 or more falls in the preceding year)
      were at greater risk of subsequent hospitalization, nursing home admission, and
      frequent physician contact than were nonfallers, after controlling for age, sex,
      self-perceived health status, and difficulties with activities of daily living.
      Similarly, one-time fallers, and especially repeated fallers, were at greater
      risk of reporting subsequent difficulties with activities of daily living,
      instrumental activities of daily living, and more physically demanding
      activities. These findings highlight the significant impact that falls have on
      the health care system and on the individual.

PMID- 1997750
TI  - Differences in rates of cancer screening by usual source of medical care. Data
      from the 1987 National Health Interview Survey.
AB  - Data from the Cancer Control Supplement of the 1987 Health Interview Survey
      (NHIS), a nationally representative sample of the United States population, was
      used to examine rates of six screening tests for cancer. The rates of screening
      were compared for people who receive their usual source of medical care in an HMO
      or prepaid group practice versus those who receive it in the fee-for-service
      sector. The purpose of this article is to determine whether HMOs remain more
      likely to offer cancer screening examinations than the fee-for-service sector.
      Results indicate that for five of six screening tests examined (Pap smear,
      mammography, breast physical examination, digital rectal examination, and blood
      stool test), members of HMOs are significantly more likely to have received the
      test within the last 3-year period. These results hold in a multivariate analysis
      when many factors correlated with selection into HMOs, health status, and use of
      medical services are controlled for, although results are only generalizable to
      whites. Future research should focus on why the rates for five of the six cancer
      screening tests examined are higher in HMO settings, and how we can use the HMO
      experience to improve consensus as to the usefulness of the tests in the non-HMO
      physician pool, and ultimately increase rates of screening tests in the non-HMO
      population.

PMID- 1997752
TI  - The Foreign Medical Graduate Examination in the Medical Sciences (FMGEMS). An
      analysis of pass rates of the July 1984 through July 1987 examinations.
AB  - This report examines the experience of 48,509 (40,393 foreign nationals and 8,116
      U.S. citizens) foreign medical students and graduates (FMGs) who took any part of
      the first seven Foreign Medical Graduate Examination in the Medical Sciences
      (FMGEMS) administered by the Educational Commission for Foreign Medical
      Graduates. The pass rate on all three sections (basic science, clinical science,
      and English) was 23.0%. Almost one-half (47.2%) of all FMGEMS examinees were
      between 25 and 29 years of age, 73.9% were men, 71.5% took FMGEMS after medical
      school graduation, and 79.7% claimed as their native tongue languages other than
      English. Correlates of pass rates included taking FMGEMS before medical school
      graduation (30.0% pass) and being a native English speaker (37.5% pass). The
      rates for foreign national FMGs (FNFMGs) and United States FMGs (USFMGs) were
      22.5% and 25.2%, respectively. Native English-speaking FNFMGs achieved a 43.3%
      pass rate; native English-speaking USFMGs, 32.6%; non-native English-speaking
      FNFMGs, 19.9%; and non-native English-speaking USFMGs, 11.2%. Whereas FMGs were
      educated in 114 countries, 74.2% of USFMGs were educated in just eight countries,
      all located in the West Indies and Mexico. Logistical regression analysis showed
      that the strongest factors predicting full pass rates were being both younger
      than 30 years of age and a native English speaker. Conclusions are that
      approximately 3,200 FMGs per year pass FMGEMS and that FMGs with the highest
      probability of passing share characteristics of U.S. and Canadian medical
      graduates who pass the National Board medical examinations, which suggests that
      the latter examinations, when offered to FMGs, may have limited effect on overall
      pass rates.

PMID- 1997753
TI  - Mail versus telephone surveys on mammography utilization among women 50-75 years
      old.
AB  - Surveys are needed to monitor trends in mammography use and to evaluate
      intervention programs aimed at increasing breast cancer screening. In a community
      based intervention project in Long Island (New York), estimated response rates
      were similar in separate random surveys of women 50-75 years old by mail and
      telephone. Respondents by mail (n = 2,368) and telephone (n = 1,011) were similar
      in distributions of age, marital status, and educational level, and mail
      respondents did not have higher income levels than telephone respondents.
      Reported utilization of breast cancer screening tests was similar by survey mode.
      A statistically significant positive association between mammography utilization
      and income level was evident in both mail and telephone surveys. These findings
      should promote the consideration of mail surveys in other studies of the
      utilization of breast cancer screening tests by various health care
      organizations.

PMID- 1997754
TI  - The effects of patient, hospital, and physician characteristics on length of stay
      and mortality.
AB  - This article compares the ability of hospital and physician characteristics to
      explain variations in length of stay and mortality, controlling for factors
      associated with severity of illness. The analysis is based on 54,571 discharges,
      covering 11 medical and five surgical conditions, from nonfederal general
      hospitals in one state during 1988. Results suggest that both hospital and
      physician characteristics are important predictors of both outcome measures.
      Contrary to previous research, the volume of patients with the same condition
      treated by the hospital increases both length of stay and mortality. The volume
      of patients with the same condition treated by the physician increases length of
      stay among patients with medical conditions, decreases length of stay among those
      with surgical conditions, and decreases mortality. One interesting finding is
      that the medical school attended by the physician influences the patient's length
      of stay. Findings are interpreted in light of research evidence on factors
      affecting medical outcomes and recent federal efforts to improve quality of care.

PMID- 1997755
TI  - Specialization among obstetrician/gynecologists. Another dimension of physician
      supply.
AB  - This study uses the Herfindahl index to investigate the specialization patterns
      of physicians. "Specialization" is defined as the degree to which an individual
      doctor concentrates his practice into a narrow range of disease categories. This
      application is the specialization pattern of office-based
      obstetrician/gynecologists in the United States. Physician's age and solo
      practice both exhibit a systematic negative effect on specialization. Both the
      age and type of practice effects reflect the tendency for younger and nonsolo
      obstetrician/gynecologists to gear relatively more of their practice into birth
      related activities. The age effect is consistent with the hypotheses that either:
      (1) energy and/or skills for treating pregnancy become more scarce with age, or
      (2) there is a life-cycle pattern in the doctor/patient relationship with
      pregnancy serving as an entry point. Malpractice concerns may also contribute to
      this age effect. The nonsolo practitioner effect suggests the efficiency of
      multiple doctor practices for allocating physicians' time in activities with high
      hourly variability in demand. The method used to measure specialization can be
      extended to investigate other specialty categories and important issues regarding
      the future supply of physicians' services. These include the effects of an aging
      physician population and proposed changes in physician reimbursement.

PMID- 1997756
TI  - Emergency room use by low income children with a regular source of health care.

PMID- 1997757
TI  - Patient involvement in health care. A procedural justice viewpoint.

PMID- 1997758
TI  - [The importance of light for health and well-being].

PMID- 1997759
TI  - [The connection of cadmium-renal injuries and skeletal decalcification].

PMID- 1997760
TI  - [Changed trends of psychological diagnosis and treatment in child psychiatry?].

PMID- 1997761
TI  - [Tonsillectomy--still a valid therapeutic method].

PMID- 1997762
TI  - [No conclusion can be drawn].

PMID- 1997763
TI  - [Unlimited antibiotic therapy in recurrent tonsillitis is alarming].

PMID- 1997764
TI  - [Treatment of hypertension. High safety of first choice agents is a requirement].

PMID- 1997765
TI  - [Decreasing number of skiing accidents in the Swedish mountains].

PMID- 1997766
TI  - [Light therapy of depression].

PMID- 1997767
TI  - [The Norrbothnian type of Gaucher's disease. Mutation diagnosis as a simple
      technique for risk determination].
AB  - Direct analysis of monogenic disorders by means of DNA sequencing, both cDNA and
      genomic DNA, combined with functional studies, has enabled the molecular basis of
      a number of diseases to be determined. The development of DNA diagnostics is of
      particular importance in clinical medicine, and wellestablished methods are now
      available for the rapid and reliable detection of specific mutations. In the
      article are presented some of the techniques used, and their application in a few
      inherited disorders. Particular attention is focused on Gaucher's disease type
      III (the subacute neuronopathic or Norrbotten type), where a single mutation has
      been found to be present in all the Swedish cases investigated. The hereditary
      background of the disease, the basic molecular defect, and detection of the
      mutation are discussed.

PMID- 1997768
TI  - [Diagnosis of cystic fibrosis with DNA techniques].
AB  - The extensive body of genetic and physical mapping data accumulated since the
      identification of the cystic fibrosis (CF) gene locus on chromosome 7 has made
      possible the molecular cloning of the gene. A deletion of three DNA base pairs,
      removing a phenylalanine residue from position 508 of the protein product,
      accounts for 40-85 per cent of CF mutations in most Western countries, the
      estimated figure for Sweden being 60 per cent. In the article are discussed
      findings for three additional mutations (G551D, R553X and G542X), only one allele
      out of 200 analysed having been found to manifest the R553X mutation alone. Also
      discussed are DNA techniques for detecting the common mutation, recent progress
      toward in vivo correction of the defect, and indications and possibilities for
      future screening programs.

PMID- 1997769
TI  - [Is the task of the UN to restore peace and safety in Lebanon hopeless?].

PMID- 1997770
TI  - [The Swedish UN hospital has given much valuable experience to physicians and
      nurses].

PMID- 1997771
TI  - [How poisonous are our spare parts?].

PMID- 1997772
TI  - [Is "amalgam disease" an autoimmune reaction?].

PMID- 1997773
TI  - [Better individual adaptation in future maternal health care. Routine check-ups
      are based on weak scientific grounds].

PMID- 1997774
TI  - Preliminary experience with the pulsed dye laser for treatment of urolithiasis.
AB  - We report our initial experience using the pulsed dye laser in 26 patients with
      urolithiasis. The patients ranged in age from 27 to 82 years; 11 patients were
      female and 15 were male. Of the 26 patients, 4 stones were in the kidney, 21 were
      in the ureter, and one was in the bladder. Surgical time ranged from 32 to 130
      minutes. All patients were treated under spinal or general anesthesia. The size
      of ureteral stones ranged from 0.2 to 1.5 cm, and the renal stones 3.0 to 4.0 cm.
      Chemical analysis of the stones was not available on all patients, but when
      available, chemical analysis revealed the stones to be calcium monohydrate,
      calcium dihydrate, or struvite. The use of the Candela miniscope in 11 patients
      permitted access without ureteral dilation. In 19 patients, ureteral stents were
      placed. One patient suffered a ureteral perforation. Success was defined as
      adequate disintegration of the stone for passage of the fragments without the
      necessity of a secondary procedure. Using this criterion, 22 of 26 patients were
      successfully treated for an overall success rate of 85%.

PMID- 1997775
TI  - Influence of probe motion on laser probe temperature in circulating blood.
AB  - The purpose of this study was to evaluate the effect of probe motion on laser
      probe temperature in various blood flow conditions. Laser probe temperatures were
      measured in an in vitro blood circulation model consisting of 3.2 nm-diameter
      plastic tubes. A 2.0 mm-diameter metal probe attached to a 300 microns optical
      quartz fiber was coupled to an argon laser. Continuous wave 4 watts and 8 watts
      of laser power were delivered to the fiber tip corresponding to a 6.7 +/- 0.5 and
      13.2 +/- 0.7 watts power setting at the laser generator. The laser probe was
      either moved with constant velocity or kept stationary. A thermocouple inserted
      in the lateral portion of the probe was used to record probe temperatures. Probe
      temperature changes were found with the variation of laser power, probe velocity,
      blood flow, and duration of laser exposure. Probe motion significantly reduced
      probe temperatures. After 10 seconds of 4 watts laser power the probe temperature
      in stagnant blood decreased from 303 +/- 18 degrees C to 113 +/- 17 degrees C
      (63%) by moving the probe with a velocity of 5 cm/sec. Blood flow rates of 170
      ml/min further decreased the probe temperature from 113 +/- 17 degrees C to 50 +/
      8 degrees C (56%). At 8 watts of laser power a probe temperature reduction from
      591 +/- 25 degrees C to 534 +/- 36 degrees C (10%) due to 5 cm/sec probe velocity
      was noted. Probe temperatures were reduced to 130 +/- 30 degrees C (78%) under
      the combined influence of 5 cm/sec probe velocity and 170 ml/min blood
      flow.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1997777
TI  - Noncontact tissue ablation by holmium:YSGG laser pulses in blood.
AB  - To assess the feasibility of intra-arterial tissue ablation by Holmium:YSGG laser
      pulses (2.1 microns) in a noncontact mode, the transmission of the laser pulses
      through saline and blood was measured. The temporal interaction between the 500
      microseconds laser pulse and saline at the fiber tip was investigated with time
      resolved flash photography. The penetration depth in blood, and saline depended
      on the fiber output energy. In blood at 37 degrees C, the penetration depth
      varied from 1.2 to 2.1 mm for intensities of 3.1 to 12.4 J/mm2 per pulse,
      respectively, whereas its theoretical value for water is 0.33 mm, which is based
      on the measured absorption coefficient of 3.0 +/- 0.1/mm. The large penetration
      depth was due to the development of a transparent vapour cavity around the fiber
      tip. In saline, its maximum length was 4.7 mm. Its maximum width was 2.8 mm. The
      lifetime of the cavity was 450 microseconds. In blood, ablation of porcine aorta
      was feasible at a distance of 3 mm. Large fissures observed in adjacent tissue
      are likely to be caused by the expansion of the vapour cavity. We conclude that,
      due to a "Moses effect in the microsecond region," Holmium:YSGG tissue ablation
      is possible through at least 2.7 mm of blood.

PMID- 1997776
TI  - Endoscopic thoracic sympathectomy: evaluation of pulsatile laser, non-pulsatile
      laser, and radiofrequency-generated thermocoagulation.
AB  - We describe a modified technique for percutaneous denervation of the thoracic
      sympathetic chain by laser to treat selected cases of sympathetic causalgia of
      the upper extremities. The technique involves transpleural ablation with laser
      under thoracoscopic guidance through the second or third intercostal space
      anterior axillary line. We also compare four different modalities of endoscopic
      denervation: A xenon chloride excimer laser (308 nm, 35 mJ/pulse, 20 pulses/sec,
      2.2 mm catheter tip), CO2 laser (14 W, CW, 2 mm spot size), Nd:YAG laser (88 W,
      CW, 3 mm spot size), and radiofrequency-generated thermocoagulation (3 W, CW, 2.1
      mm catheter tip) by performing bilateral thoracic sympathectomy on 12 mongrel
      dogs (three dogs each). Criteria analyzed included duration of exposure, power
      density, total energy output, laser penetration and spread, gross morphology, and
      scanning electron microscopy (SEM) of the destroyed neural tissue. Total ablation
      of the inferior segment of the stellate ganglion and the T1-T2 nerve roots by
      excimer laser required 83 +/1 1 Joules over an exposure period of 118 seconds.
      Ablation by CO2 and Nd:YAG laser required 153 +/- 13 Joules and 554 +/- 47 Joules
      delivered over 11 and 6 seconds respectively. In contrast, ablation of the same
      volume of nerve tissue by RF required 810 +/- 50 Joules over 270 seconds. SEM
      evaluation revealed that excimer and CO2 laser lesions were narrower in
      configuration compared to RF and Nd:YAG lesions which showed more lateral spread.
      The actual depth of penetration per 1 second exposure was similar for Excimer and
      CO2 (1.5 mm) and RF (1.3 mm), but deeper for Nd:YAG (3 mm).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1997778
TI  - Direct CO2 laser "revascularization" of the myocardium.
AB  - Evidence of regional myocardial perfusion and contractile function after direct
      CO2 laser myocardial revascularization (DLR) is lacking. We examined myocardial
      segment shortening, adenine nucleotide concentrations, and regional blood flow
      after DLR of the left anterior descending coronary artery (LAD) distribution
      before and after its proximal ligation in seven anesthetized conditioned dogs.
      Sonomicrometry assessed myocardial fiber shortening and radioactive microspheres
      were used to estimate baseline regional blood flows. Cardiopulmonary bypass was
      followed by cardioplegia arrest. Laser channels (1 mm diameter) were made every 3
      to 5 mm in the LAD region with an 80 watt Laser-sonics CO2 unit. Bypass was
      terminated, the LAD occluded, and parameters reassessed. Core samples of
      myocardium from the lased LAD and control circumflex area were taken to assess
      adenine nucleotides. After occlusion, LAD distribution blood flow and myocardial
      shortening were reduced to pre-lasting ischemic controls. Adenine nucleotides
      were reduced in the LAD region relative to the control CMX area. DLR cannot be
      relied upon to acutely revascularize the ischemic myocardium.

PMID- 1997779
TI  - Bladder perforation resulting from the use of the neodymium:YAG laser.
AB  - Complications resulting from the use of the neodymium:YAG (Nd:YAG) laser to treat
      superficial bladder cancer are uncommon and are usually associated with
      abnormally high laser power outputs. We report a case of bladder perforation in a
      human attributed to the Nd:YAG laser used at a low power setting and comment on
      those factors that contributed to this complication.

PMID- 1997780
TI  - 193 nm excimer laser ablation of bone.
AB  - The argon fluoride excimer laser is investigated as a cutting-ablating tool for
      bone surgery. Quantitative measurements are presented for various fluences of
      laser energy and number of pulses. Histological data are presented that
      demonstrate the minimal damage to the surrounding material from the laser
      interaction. Comparisons are made for non-decalcified and decalcified bone. The
      differences observed, as a function of decalcification in the fluences required
      for specified depth penetration, are noted and a possible explanation is
      suggested.

PMID- 1997781
TI  - Effects of CO2 laser beam on cortical bone.
AB  - Sixteen bone blocks from two freshly amputated legs were used to study the effect
      of CO2 laser on cortical bone. They were divided into two groups. In Group I, the
      blocks were treated with CO2 laser using 1 mm spot (focused mode). In Group II,
      they were treated with CO2 laser using 3 mm spot (defocused mode). Two other
      variables were investigated: the power and time of exposure. Three histologic
      zones were observed: a superficial zone with black particle deposits
      (carbonization), an intermediate zone with fibrillations and enlarged empty
      lacunae, and a deep zone with normal appearing bone. The bony changes in the
      first two zones combined were superficial in all specimens and did not exceed 200
      microns. Increased energy, a focused beam, and time of exposure were all
      associated with increased matrix changes. CO2 laser can be applied to cortical
      bone in vitro with minimal residual thermal damage.

PMID- 1997782
TI  - Laser-induced photoacoustic injury of skin: effect of inertial confinement.
AB  - Argon-fluoride (ArF) excimer laser-induced acoustic injury was confirmed by
      ablating the stratum corneum (s.c.) inertially confined by water in vivo.
      Hairless rats were irradiated through a quartz chamber with flowing distilled
      water or air and a 2.5 mm aperture. The laser was adjusted to deliver 150 mJ/cm2
      at the skin surface for both conditions. Partial and complete ablation of the
      s.c. was achieved with 12 and 24 pulses, respectively. Immediate damage was
      assessed by the transmission electron microscopy. Partial ablation of the s.c.
      through air produced no damage, whereas partial ablation through water damaged
      skin to a mean depth of 114.5 +/- 8.8 microns (+/- SD). Full thickness ablation
      of the s.c. through air and water produced damage zones measuring 192.2 +/- 16.2
      and 293.0 +/- 71.6 microns, respectively (P less than 0.05). The increased depth
      of damage in the presence of inertial confinement provided by the layer of water
      strongly supports a photoacoustic mechanism of damage. The damage induced by
      partial ablation of the s.c. provides evidence that photochemical injury is not a
      significant factor in the damage at a depth because the retained s.c. acts as a
      partial barrier to diffusion of photochemical products. Combined with our
      previous studies, these experiments demonstrate that pressure transients are
      responsible for the deep damage seen with 193 nm ablation and that photoacoustic
      effects must be considered when using short-pulse, high-peak power lasers.

PMID- 1997783
TI  - Generation of "soft x-rays" by using the free electron laser as a proposed means
      of diagnosing and treating breast cancer.
AB  - The diagnosis and treatment of breast lesions may be markedly enhanced by the use
      of a unique new source of near-monochromatic x-rays. Concentric beams of near
      monochromatic x-ray photons may be generated by collision of the free electron
      laser (FEL) electron beam with the optical beam in an interaction zone that
      delivers the x-rays to a shirtsleeve environment. The absence of Compton scatter
      and the photoelectric interaction within tissues improves conspicuity of lesions
      by two to six times. Increased attenuation of x-rays in malignant vs. normal
      tissues makes tumors more obvious. K-edge subtraction allows chemical analysis of
      tumors in vivo--all at radiation doses that are one-tenth to one-fiftieth that
      delivered by the lowest-dose mammographic x-ray technique available. This allows
      for an increased sensitivity and specificity and permits prediction of histology,
      negating necessity for biopsies. Selective bond-breaking at depth in tissues as
      well as x-ray-activated photodynamic therapy are also being explored.

PMID- 1997784
TI  - Cloning and sequencing of a human liver carboxylesterase isoenzyme.
AB  - A human liver lambda gt11 library was screened with antibodies raised to a
      purified rat liver carboxylesterase, and several clones were isolated and
      sequenced. The longest cDNA contained an open reading frame of 507 amino acids
      that represented 92% of the sequence of a mature carboxylesterase protein. This
      sequence possessed many structural features that are highly conserved among
      rabbit and rat liver carboxylesterase proteins, including Ser, His, and Asp
      residues that comprise the active site, two pairs of Cys residues that may
      participate in disulfide bond formation, and one Asn-Xxx-Thr site for N-linked
      carbohydrate addition. When the clone was used to probe human liver genomic DNA
      that had been digested with various restriction enzymes, many hybridizing bands
      of differing intensities were observed. The results suggest that the
      carboxylesterases exist as several isoenzymes in humans, and that they are
      encoded by multiple genes.

PMID- 1997785
TI  - The toxicity of methanol.
AB  - Methanol toxicity in humans and monkeys is characterized by a latent period of
      many hours followed by a metabolic acidosis and ocular toxicity. This is not
      observed in most lower animals. The metabolic acidosis and blindness is
      apparently due to formic acid accumulation in humans and monkeys, a feature not
      seen in lower animals. The accumulation of formate is due to a deficiency in
      formate metabolism which is, in turn, related, in part, to low hepatic
      tetrahydrofolate (H4 folate). An excellent correlation between hepatic H4 folate
      and formate oxidation rates has been shown within and across species. Thus,
      humans and monkeys possess low hepatic H4 folate levels, low rates of formate
      oxidation and accumulation of formate after methanol. Formate, itself, produces
      blindness in monkeys in the absence of metabolic acidosis. In addition to low
      hepatic H4 folate concentrations, monkeys and humans also have low hepatic 10
      formyl H4 folate dehydrogenase levels, the enzyme which is the ultimate catalyst
      for conversion of formate to carbon dioxide. This review presents the basis for
      the role of folic acid-dependent reactions in the regulation of methanol
      toxicity.

PMID- 1997786
TI  - Influence of fibric acid derivatives on intermediate filament proteins in
      myocardiocyte cultures.
AB  - We analyzed desmin and vimentin accumulation in chick myocardiocyte cultures
      treated with the fibric acid derivatives bezafibrate, fenofibrate and
      gemfibrozil. The most noteworthy finding was the 50% decrease in the cytoplasmic
      desmin fraction in cells treated with gemfibrozil in comparison to control
      cultures, and the 19% increase in the cytoskeletal fraction in cultures treated
      with gemfibrozil and with bezafibrate. Vimentin accumulation by cells treated
      with bezafibrate was similar to that in control cultures, however the
      cytoskeletal vimentin fraction rose by 26% after treatment with gemfibrozil, and
      fell 13% after treatment with fenofibrate. No vimentin was found in the
      cytoplasmic fraction of cell treated with bezafibrate. Given the role of
      intermediate filaments in heart muscle contraction, fibric acid derivative-
      induced changes in the cytoplasmic and cytoskeletal concentrations of
      intermediate filament proteins may be related with the secondary effects of these
      drugs on heart rate.

PMID- 1997787
TI  - Phospholipase D in cell signalling and its relationship to phospholipase C.
AB  - Phospholipases C and D are phosphodiesterases which act on phospholipid head
      groups. Although the presence of these enzymes in living organisms has long been
      known, it is only recently that their role in cell signal transduction has been
      appreciated. The new developments on phospholipases D (PLD) are especially
      noteworthy, since these enzymes catalyze a novel pathway for second messenger
      generation. In a variety of mammalian cell systems, several biological or
      chemical agents have recently been shown to stimulate PLD activity. Depending on
      the system, activation of PLD has been suggested to be either dependent on, or
      independent of, Ca2+ and protein kinase C. PLD primarily hydrolyses
      phosphatidylcholine (PC) but phosphatidylinositol and phosphatidylethanolamine
      have also been reported as substrates. Different forms of endogenous PLD may also
      exist in cells. Exogenous addition of PLD causes alterations in cellular
      functions. In many instances, Ca2+ mobilizing agonists may stimulate both PLC and
      PLD pathways. Interestingly, several metabolites of these two enzymes are second
      messengers and are common to both pathways (e.g. phosphatidic acid, diglyceride).
      This has raised the issue of the interrelationship between these pathways. The
      regulation of either PLC or PLD by cellular components, e.g. guanine nucleotide
      binding proteins or protein kinases, is under intense investigation. These recent
      advances are providing novel information on the significance of phospholipase C
      and D mediated phospholipid turnover in cellular signalling. This review
      highlights some of these new discoveries and emerging issues, as well as
      challenges for future research on phospholipases.

PMID- 1997788
TI  - Effect of indomethacin on opioid-induced gastric protection in cold-restrained
      stress.
AB  - Morphine and the synthetic opioid met-enkephalin analog [D-Ala2, MePhe4,
      Met(0)5ol] enkephalin (FK 33-824) injected intraperitoneally to rats at doses of
      5-20 and 0.5-2 mg/kg respectively showed a protective effect on gastric lesion
      induced by cold-restraint stress. This protective effect was abolished by
      pretreatment with indomethacin. This suggests a role for prostaglandins in the
      protection, induced by opioids of the gastric mucosa against the development of
      stress-induced ulcers.

PMID- 1997790
TI  - Effect of restraint stress on prolactin and corticosterone levels in
      streptozotocin-induced diabetic rats.
AB  - Changes in neuroendocrine function have been shown to occur in diabetic animals.
      The aim of the present study was to examine both the prolactin (PRL) and
      corticosterone (CORT) responses to a short period of restraint stress after the
      animals had been made diabetic for six weeks. The streptozotocin - induced
      diabetic rats had resting CORT levels which were significantly higher than the
      control animals. Acute restraint significantly increased CORT levels in both the
      control and diabetic rats. The CORT levels after stress were higher in the
      diabetic rats. However, the magnitude of the response (percent increase) was less
      in these animals. The resting PRL levels were not significantly different in the
      diabetic and control animals. The PRL levels significantly increased in both the
      control and diabetic rats when they were exposed to the restraint stress. The PRL
      levels after stress were significantly less in the diabetic rats, indicating a
      blunted PRL stress response. These results indicate that the diabetic state can
      affect an animals PRL and CORT response to a new acute stress.

PMID- 1997789
TI  - Autonomic stimulation of short circuit current in swine trachea.
AB  - Autonomic stimulation of ionic fluxes was studied in tracheal epithelium of
      weanling swine by measuring short circuit current (ISC) in an Ussing chamber.
      Basal currents were predominantly secretory since 0.1 mM diphenylamine 2
      carboxylic acid (DPC) reduced currents by twice as much as did 10 microM
      amiloride. Both acetylcholine (ACh) and isoproterenol (ISO) produced a sustained
      increase in ISC, with the EC50 for ISO being 149 nM and for ACh being 500 nM. In
      both cases, the induced currents were predominantly secretory since 10 microM
      amiloride had little effect on either agonist-induced delta ISC whereas DPC
      inhibited the ISO- and ACh-induced delta ISC's by 30% and 47% respectively.
      However, responses to ACh and ISO could be distinguished on three grounds. [1] An
      anatomic gradient existed with smaller responses to agonists being observed
      towards the distal trachea. The ISO-induced currents showed a steeper gradient
      than the ACh-induced currents. [2] In single tissue samples, the size of the ISO
      induced delta ISC was not correlated with the size of the ACh-induced delta ISC.
      [3] The magnitude of the delta ISC induced by ACh was unaffected by a concomitant
      stimulation of ISC by ISO. Thus, ACh-induced secretion was independent of ISO
      induced secretion, and likely occurred in different cell types.

PMID- 1997791
TI  - Conversion of p-tyrosine to p-tyramine in the isolated perfused rat kidney:
      modulation by perfusate concentrations of p-tyrosine.
AB  - We used the isolated perfused rat kidney to evaluate the role of renal
      decarboxylation of p-tyrosine as the source of urinary p-tyramine. Kidneys were
      perfused with concentrations of p-tyrosine ranging from 0.02 mM to 2.0 mM. p
      Tyramine was measured by a sensitive and specific radioenzymatic assay. An
      increase in the perfusate concentration of p-tyrosine resulted in a significant
      increase in p-tyramine production that was blocked by the addition of NSD-1015,
      an inhibitor of aromatic-1-amino decarboxylase (AADC). We conclude p-tyrosine is
      the precursor for the renal production of p-tyramine, renal AADC catalyzes the
      formation of urinary p-tyramine, synthesized p-tyramine is predominantly excreted
      in the urine, and p-tyramine synthesis is modulated by the arterial delivery of p
      tyrosine to the kidney.

PMID- 1997792
TI  - Thyroidal involvement in the expression of avian muscular dystrophy.
AB  - We showed previously that propylthiouracil (PTU), a thyroid inhibitor, could
      alleviate several major signs of hereditary muscular dystrophy in chickens. The
      goals of the present investigation were to: (1) determine whether a nearly
      athyroid condition (achieved within two days after hatching by surgical
      thyroidectomy plus PTU) during an 11-day period beneficially affects the
      dystrophic condition when followed by triiodothyronine (T3) replacement to 33
      days of age; (2) determine the beneficial effects on the expression of avian
      dystrophy when the thyroidectomized-PTU-treated chickens received a wide range of
      moderate to low T3 replacement doses beginning by two days after thyroidectomy;
      and (3) examine the thyroid hormone receptor system in dystrophic muscle for a
      possible abnormality. Thyroid deprivation increased muscle function (righting
      ability) and reduced plasma creatine kinase activity in dystrophic chickens. The
      major thyroid-related abnormality in dystrophic pectoralis muscles was an
      increased maximum binding capacity of solubilized nuclear T3 receptors.

PMID- 1997793
TI  - Interleukin-1 stimulates the release of dopamine and dihydroxyphenylacetic acid
      from the hypothalamus in vivo.
AB  - Push-pull perfusion technique was used to infuse IL-1 beta into and collect
      perfusate from the medial basal hypothalamus of freely moving male rats. Dopamine
      (DA) and its metabolite, dihydroxyphenylacetic acid (DOPAC), were measured in the
      perfusate using high performance liquid chromatography with electrochemical
      detection. In the control group, release rates of DA and DOPAC decreased and were
      62% and 40%, respectively, below pretreatment levels after 325 min. In contrast,
      treatment with 50 ng of IL-1 beta produced substantial reductions in these
      decreases, and treatment with 100 ng of IL-1 beta produced increases of up to
      118% and 89% in the release rates of DA and DOPAC, respectively. It is concluded
      that IL-1 beta affects the metabolism of catecholamines (and probably other
      neurotransmitters) in the brain, which, in turn, mediate its central and
      neuroendocrine actions.

PMID- 1997794
TI  - Magnetic resonance imaging diagnosis of an intracranial metastasis of
      adenocarcinoma of the prostate: case report.
AB  - Adenocarcinoma of the prostate is the second most common cancer of American males
      over age fifty. However, the reported instances of cerebral metastases have been
      exceedingly rare and are usually diagnosed at postmortem. This report describes
      an unusual case of brain metastasis from an occult adenocarcinoma of the prostate
      confirmed by craniotomy and tumor resection.

PMID- 1997795
TI  - Medical advertising.

PMID- 1997796
TI  - Lyme disease.

PMID- 1997797
TI  - Conservative treatment of adenocarcinoma of the lower rectum.

PMID- 1997798
TI  - Management of hypoglycemic reactions in obese non-insulin-dependent diabetes
      patients.

PMID- 1997799
TI  - Blood tests in the diagnosis of connective tissue diseases.
AB  - Making the diagnosis of connective tissue disease can at times be extremely
      difficult. Obtaining a complete rheumatological and medical history, and
      performing a thorough physical examination are absolutely essential. This article
      has reviewed several of the laboratory parameters which can aid the clinician in
      the differential diagnosis of connective tissue diseases. Which tests should be
      ordered in any given individual patient should be determined by the clinical
      setting. Careful evaluation of the laboratory data, in the context of the
      patient's history and physical examination, should, in general, allow the
      clinician to make the proper rheumatological diagnosis.

PMID- 1997800
TI  - Writing a newsletter.

PMID- 1997801
TI  - Research commentary: research readiness.

PMID- 1997802
TI  - Anabolic steroid-induced tendon pathology: a review of the literature.
AB  - Anabolic steroids have attained a prominent, albeit highly controversial,
      position among ergogenic aids for power athletes. Adverse effects of these
      compounds are well documented, but their popularity persists. One of their
      possible side effects which has received little attention is abnormal form and
      function of connective tissue in steroid-abusing athletes. Scientific and medical
      literature addressing this concern is scant and is generally limited to observed
      effects in animals. Anabolic steroid use paralleled with exercise may lead to
      dysplasia of collagen fibrils, which can decrease the tensile strength of tendon.
      Changes in tendon's crimp morphology have been shown to occur, as well, which may
      alter the rupturing strain of tendon and the normal biomechanics of the
      extremities. Given the megadoses of steroids taken by some athletes and the large
      forces incurred by power-trained musculature, the integrity of tendinous tissue
      in these athletes may be at significant risk of compromise if steroids do, in
      fact, exert a destructive effect. Additional investigation in the area reviewed
      here is warranted before anabolic steroids can be decisively implicated in human
      connective tissue disruption. It is recommended, however, that consideration be
      given to including potential tissue alterations among the side effects of steroid
      abuse.

PMID- 1997803
TI  - Static pre-load effect on knee extensor isokinetic concentric and eccentric
      performance.
AB  - The effect of two static pre-load levels on isokinetic concentric (CON) and
      eccentric (ECC) performance of the knee extensors at 90 degrees.s-1 was evaluated
      in 35 healthy subjects. The low pre-load level was 50 N, and the high level was
      75% of a maximal voluntary isometric contraction, performed at the start angles
      of 100 degrees (CON) and 30 degrees (ECC) of knee flexion. A two-way ANOVA with
      two repeated measures (load and angle) and a Newman-Keuls post hoc analysis were
      performed to compare the interaction of pre-load and angle at every 5 degrees in
      the ROM. The differences in average torque, peak torque, and peak torque angle
      between the pre-load levels were also analyzed with repeated-measures t-tests.
      The high pre-load condition had a significant increase in torque at 99, 95, 90,
      and 85 degrees concentrically and 31, 35, 40, 45, and 50 degrees eccentrically.
      In comparing the two pre-load conditions over the whole torque curve, there was a
      significant difference in average torque values of both CON and ECC, no
      significant difference in peak torque in either contraction, and a significant
      shift in peak torque angle with CON contractions only.

PMID- 1997804
TI  - A comparison of knee extensor strength curves obtained theoretically and
      experimentally.
AB  - Strength curves relate a measure of maximal voluntary force of a group of
      synergistic muscles, typically a resultant knee joint moment, to a measure of
      muscular length, typically a joint angle. In this study, it was hypothesized that
      the shape of strength curves is primarily determined by the force-length
      properties of the individual muscles within a synergistic group. This hypothesis
      was tested for knee extensor strength curves by comparing theoretically
      determined strength curves based on the force-length relations of the individual
      muscles with those obtained experimentally. The agreement between theoretical and
      experimental curves was good, suggesting that the initial hypothesis was correct.
      Accepting this result, it is possible to determine the contribution of individual
      muscles to the total force of the synergistic group. This information, in turn,
      may be utilized for practical applications in sports or for evaluating strength
      curves of patients with injuries or diseases of the musculoskeletal system.

PMID- 1997805
TI  - Fifteen-year changes in exercise, aerobic power, abdominal fat, and serum lipids
      in runners and controls.
AB  - To describe effects of past as well as current exercise, aerobic power, and
      subcutaneous fat on the serum lipid profile, two groups of former elite athletes
      (N = 27 runners, N = 9 bobsledders) and a control group of normal men (N = 23)
      were investigated. Analysis of variance indicated a significant effect of the
      type of sports activity on HDL cholesterol, apolipoprotein A-I, and triglyceride
      levels and on the LDL/HDL cholesterol and apolipoprotein B/A-I ratios, with the
      most favorable values seen in runners and the least favorable values seen in
      controls. Of the 27 former elite runners, one third (N = 9) had given up or
      strongly reduced training. This subgroup showed the steepest 15-yr decrease (from
      1973 to 1988) in maximum aerobic power and the largest 15-yr increase in
      subcutaneous fat, and the lipid profile (measured in 1988) corresponded more to
      the one of bobsledders and controls than to the one of runners who had remained
      active. Separate correlational analyses of all runners (N = 27) and nonrunners (N
      = 32) showed that, in both cohorts, i) the 1988 measurements of exercise, aerobic
      power, and subcutaneous fat were more predictive for the lipid profile in 1988
      than the corresponding 1973 values, ii) anthropometric characteristics,
      especially abdominal fat, had a stronger relation with serum lipid concentrations
      than exercise and aerobic power, and iii) 15-yr changes in anthropometric
      characteristics were, but 15-yr changes in exercise and aerobic power were not,
      associated with triglyceride, lipoprotein, and apolipoprotein levels in
      1988.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1997806
TI  - The influence of electrocortical biofeedback on performance in pre-elite archers.
AB  - The purpose of the present research was to determine whether EEG biofeedback
      training could improve archery performance as well as self-reported measures of
      concentration and self-confidence. Experienced pre-elite male (N = 16) and female
      (N = 8) archers were randomly assigned to one of three treatment conditions: (a)
      correct feedback (i.e., greater left hemisphere low frequency activity), (b)
      incorrect feedback (i.e., greater right hemisphere low frequency activity), and
      (c) no feedback control. The pretest and posttest consisted of 27 shots, with EEG
      data collected for the left and right temporal hemispheres (T3, T4). Feedback
      subjects were then given EEG biofeedback, while control subjects rested for 30
      min. Analyses indicated that only the performance measure was significant. The
      correct feedback group significantly improved performance, while the incorrect
      feedback group showed a significant performance decrement from pre- to posttest
      (Ps less than 0.05). The control group showed no significant pre-post differences
      in performance. EEG analyses showed differences that were consistent with the
      training given to the incorrect, but not the correct, feedback group. Overall,
      the results provide some support for the use of known relationships between EEG
      and performance as an effective means of providing biofeedback to affect the
      performance of pre-elite archers.

PMID- 1997807
TI  - A segment interaction analysis of proximal-to-distal sequential segment motion
      patterns.
AB  - The purpose of this study was to examine the motion-dependent interaction between
      adjacent lower extremity segments during the actions of kicking and the swing
      phases of running and walking. This was done to help explain the proximal-to
      distal sequential pattern of segment motions typically observed in these
      activities and to evaluate general biomechanical principles used to explain this
      motion pattern. High speed film data were collected for four subjects performing
      each skill. Equations were derived which expressed the interaction between
      segments in terms of resultant joint moments at the hip and knee and several
      interactive moments which were functions of gravitational forces or kinematic
      variables. The angular motion-dependent interaction between the thigh and leg was
      found to play a significant role in determining the sequential segment motion
      patterns observed in all three activities. The general nature of this interaction
      was consistent across all three movements except during phases in which there
      were large differences in the knee angle. Support was found for the principle of
      summation of segment speeds, whereas no support was found for the principle of
      summation of force or for general statements concerning the effect of negative
      thigh acceleration on positive leg acceleration. The roles played by resultant
      joint moments in producing the observed segment motion sequences are discussed.

PMID- 1997808
TI  - Resting metabolic rate and energy balance in amenorrheic and eumenorrheic
      runners.
AB  - This study investigated metabolic and nutritional factors in association with
      athletic menstrual dysfunction (AMD). Three groups of women were studied:
      amenorrheic runners (amenorrheic), eumenorrheic runners (eumenorrheic), and
      eumenorrheic sedentary controls (sedentary). Amenorrheic and eumenorrheic were
      similar in age, weight, percent body fat by hydrodensitometry, training pace and
      mileage, best 10 km race time, years running, and maximal oxygen consumption.
      When adjusted for body weight or for fat-free mass by analysis of covariance, RMR
      was significantly lower in amenorrheic than in eumenorrheic and sedentary. The
      daily caloric intakes of the groups did not differ significantly, but the
      amenorrheic scored significantly higher than the eumenorrheic and sedentary on a
      scale of aberrant eating patterns. Amenorrheic high mileage runners seem to have
      a less adequate diet than eumenorrheic runners but appear to maintain energy
      balance and stable weight through a reduction in RMR.

PMID- 1997809
TI  - Body composition and sexual maturation in premenarcheal athletes and nonathletes.
AB  - The purpose of this study was to compare premenarcheal athletes (A) and
      nonathletes (NA) in terms of body composition and sexual maturation and to
      discern the relationship between these variables. Percent body fat (%BF) was
      determined by the three-component system of Siri utilizing body density from
      hydrostatic weighing and total body water measured by deuterium oxide dilution.
      Sexual maturation was self-assessed using the system described by Marshall and
      Tanner. ANOVAs and polynomial regression analysis revealed that both the A (N =
      73) and NA (N = 53) showed similar values and linear increases (P less than
      0.001) in height (HT), weight (WT), breast (B) and pubic hair (PH) development
      from 7 to 15 yr but not in %BF (XA = 15.7 +/- 4.6; XNA = 20.5 +/- 6.4 (P less
      than 0.001]. The NA exhibited a quadratic curve (P less than 0.01) in %BF over
      age, while the A showed a negative linear relationship (P less than 0.001) with
      age. Scheffe post hoc tests revealed significant differences (P less than 0.03, A
      less than NA) at 11 and 12-15 yr. When %BF was compared to maturation, the A were
      found to have less fat (P less than 0.01) at stages 1 and 4 of PH and at stages
      2, 3, and 4 of B. There were no significant differences between A and NA in the
      age at which B2, 3, or 4 or PH2, 3, or 4 occurred. Both groups exhibited similar
      and significant correlations between age, HT, WT, B, and PH development but not
      %BF.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1997810
TI  - Menstrual function and eating behavior in female recreational weight lifters and
      competitive body builders.
AB  - A group of 103 female weight lifters (WL) and 92 control (C) women answered a
      survey concerning eating behavior and attitudes (including the Eating Disorder
      Inventory) and menstrual function. The incidence of menstrual dysfunction,
      defined as oligomenorrhea plus amenorrhea, was significantly higher for the WL
      (30%) than for the C (13%) not on contraceptive pills. Only 2% of the women had
      amenorrhea. The incidence of dysfunction was highest for the subset of 12 WL who
      had competed in at least one body building competition (COMP); 86% of the COMP
      not on birth control pills had menstrual dysfunction (P less than 0.05). More WL
      than C reported missing at least one menstrual period during the last year (P =
      0.06). WL scored significantly higher than C on the Drive for Thinness subscale
      of the Eating Disorder Inventory (EDI). Fifteen percent of the WL and 9% of the C
      achieved the criteria on this subscale for being weight preoccupied (P greater
      than 0.05). Significantly more WL than C responded that they were terrified of
      becoming fat (WL 56%, C 38%), were obsessed with food (WL 47%, C 30%), used
      laxatives for weight control (WL 14%, C 1%), and claimed that they had been
      anorexic in the past (WL 17%, C 5%). Examination of the answers of COMP revealed
      several items that were significantly different from the remainder of the WL. For
      example, 42% used to be anorexic, 67% were terrified of becoming fat, and 50%
      experienced uncontrollable urges to eat.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1997811
TI  - Effects of warm-up on muscle glycogenolysis during intense exercise.
AB  - This study investigated the effects of preliminary exercise (warm-up) on glycogen
      degradation and energy metabolism during intense cycle ergometer exercise. After
      determination of VO2max, six male subjects were randomly assigned to perform warm
      up (WU) and no warm-up (NWU) trials incorporating a 2 min standardized sprint
      ride (SR) at 120% of the power output attained at VO2max (POmax). Muscle biopsies
      and temperature (Tm) recordings were obtained from the vastus lateralis muscle.
      Tm was elevated above the resting level prior to the SR during the WU trial (37.7
      +/- 0.1 vs 35.4 +/- 0.4 degrees C; P less than 0.05) and remained higher than the
      NWU trial after the SR (38.6 +/- 0.2 vs 37.1 +/- 0.4 degrees C; P less than
      0.05). Similar trends existed for rectal temperature (Tr). The increases in Tm
      and Tr during the SR were both greater in the NWU trial (P less than 0.05).
      Muscle glycogen degradation was similar for the WU and NWU trials (30.8 +/- 3.7
      vs 25.6 +/- 3.7 mmol.kg-1, respectively). When blood and muscle lactate
      concentrations after the SR were expressed relative to values before the SR, the
      WU trial resulted in a lower accumulation of blood lactate (6.5 +/- 0.9 vs 10.7
      +/- 0.8 mEq.l-1; P less than 0.01) and muscle lactate (20.1 +/- 0.1 vs 23.4 +/-
      2.2 mEq.kg-1 wet wt.; P less than 0.05). Furthermore, oxygen consumption during
      the 1st min of the SR was higher in the WU trial (2.3 +/- 0.2 vs 1.9 +/- 0.2
      l.min-1; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1997812
TI  - Thigh muscle function after partial tear of the medial ligament compartment of
      the knee.
AB  - The purpose of the study was to assess the isokinetic and isometric strength and
      power profile of the knees of 48 patients who had a previous second-degree sprain
      (partial tear) of the medial ligament compartment, the most common knee ligament
      injury in sports. The CYBEX II isokinetic dynamometer was used in the
      measurements. On an average of 8 yr after the injury, the mean strength deficit
      of the injured knees was minimal: 4 +/- 5% (range 0-28%) in extension and 2 +/-
      4% (0-20%) in flexion. The average strength score (max. 100 points) was 90 +/- 11
      (56-100), representing an excellent classification. In hamstrings, the relative
      strength deficit increased significantly with a higher speed of isokinetic
      movement (P less than 0.05). Compared with the strength parameters (peak
      torques), the other functional parameters of the injured knees (total work,
      average power, and peak torque acceleration energy) showed some but not
      significantly greater deficits (hamstrings 9-11%, quadriceps 6-8%). In
      conclusion, the general thigh muscle function in knees with old second-degree
      sprain of the medial ligament compartment appears good and acceptable, but the
      strength deficits are systematically greater in higher speeds of isokinetic
      movement. Therefore, rehabilitation utilizing high speed extension and flexion
      exercises is recommended.

PMID- 1997813
TI  - Skeletal muscle following tonic overload: functional and structural analysis.
AB  - Functional overloading of skeletal muscle induces a compensatory hypertrophy as
      an adaptive response to increased functional demand. Overload of the extensor
      digitorum longus (EDL) muscle (129 ReJ strain male mouse) was induced by
      unilateral surgical removal of a synergistic muscle, tibialis anterior (TA).
      Response of the EDL to overload for 7, 21, and 42 d was analyzed for changes in
      1) muscle weight, 2) myofiber type distribution, 3) myofiber cross-sectional area
      by fiber type, 4) speed of contraction and relaxation of the muscle, 5) force of
      contraction, and 6) myofiber morphologic integrity. The weight of the EDL
      significantly increased. The overload caused no impairment of muscle
      contractility and did not have a significant effect on isometric twitch
      contraction time to peak tension or the time to one-half relaxation of the
      twitch. Overloaded muscles demonstrated a transient shift in fiber type profile
      with preferential hypertrophy of Type IIA fibers that occurred in the early phase
      of overload while type IIB fibers were recruited by 42 d. No significant increase
      in myofiber number in overloaded muscles occurred. Some morphologic changes in
      over-loaded muscles parallel those found in patients with neurogenic muscular
      disorders. However, overloaded muscle did not exhibit a significant occurrence of
      fiber branching from controls in the midbelly region of the muscle.

PMID- 1997814
TI  - The effects of moderate exercise training on immune response.
AB  - The relationship between moderate exercise training (ET) (five 45-min sessions
      per week, brisk walking at 60 heart rate reserve for 15 wk) and changes in immune
      system variables and function was investigated in a group of 36 sedentary, mildly
      obese women. The study was conducted using a two (exercise (EX) and nonexercise
      (NEX) groups) by three (baseline, 6 wk, and 15 wk testing sessions) factorial
      design, with data analyzed using repeated measures ANOVA. The pattern of change
      over time between groups for number of peripheral blood lymphocytes (total), T
      cells (CD5), B cells (CD20), and serum IgG, IgA, and IgM levels was significantly
      different. This was not the case for spontaneous blastogenesis or number of T
      helper/inducer cells (CD4) or T cytotoxic/suppressor cells (CD8). Within-EX-group
      changes were characterized by significant decreases in percentage and number of
      total lymphocytes, and in T cell number after 6 wk, and significant increases in
      each of the serum immunoglobulins after both 6 and 15 wk of training. B cell
      number increased significantly in NEX subjects relative to baseline values at
      both 6 and 15 wk, with no significant changes experienced in EX subjects. In
      summary, these data suggest that moderate ET is not associated with an
      improvement in lymphocyte function but is associated with a 20% increase in serum
      immunoglobulins and several small changes in circulating numbers of immune system
      variables, highlighted by significant decreases in circulating numbers of
      lymphocytes, particularly the T cell subpopulation. These changes were especially
      apparent after 6 wk of training, with some attenuation by 15 wk.

PMID- 1997815
TI  - Oxygen uptake and heart rate responses during hypoxic exercise in children and
      adults.
AB  - Control of ventilation and heart rate during exercise appears to undergo
      maturation, while aerobic metabolism (VO2) may not. Since we had previously found
      that hypoxia during exercise produced different ventilatory responses in children
      (C) compared to adults (A), we hypothesized that VO2 and heart rate kinetics
      during exercise would show similar maturational responses to hypoxia. To test
      this hypothesis, we examined the responses during progressive (ramp) and constant
      work rate tests in children and adults breathing either room air or hypoxic gas
      (FiO2 = 0.15). When corrected for body weight, children and adults had similar
      values for lactic acidosis threshold (LAT) (C: 29.1 +/- 5.0 ml.min-1.kg-1; A:
      27.9 +/- 4.3) and VO2max (C: 40.7 +/- 8.6 ml.min-1.kg-1; A: 45.2 +/- 6.7) during
      normoxia. Hypoxia significantly lowered LAT (C: 27.5 +/- 5.4 ml.min-1.kg-1; A:
      23.2 +/- 3.8; both P less than 0.05) and VO2max (C: 37.7 +/- 8.3 ml.min-1.kg-1;
      A: 40.1 +/- 5.3; both P less than 0.05) in both children and adults. Metabolic
      efficiency (delta VO2/delta work rate) and the VO2-heart rate relationship (delta
      VO2/delta HR/kg) were similar in the two groups and unaffected by hypoxia. During
      the constant work rate exercise, VO2 kinetics (time constant during phase 2 of
      the response (pi 1) and the O2 deficit) were similar between children and adults
      and were significantly slowed by hypoxia, consistent with current understanding
      of the control of oxidative metabolism. Finally, heart rate was increased at rest
      and during exercise with hypoxia, while the time to reach 75% of the end-exercise
      response was delayed significantly, in both groups.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1997816
TI  - Perceptual responses and blood lactate concentration: effect of training state.
AB  - The present study investigated the effect of training state on ratings of
      perceived exertion obtained at the lactate threshold (LT) and fixed blood lactate
      concentrations (FBLC) of 2.0, 2.5, and 4.0 mM. Runners (N = 20) and nonrunners (N
      = 29) completed a progressive horizontal treadmill (TM) running test which
      allowed identification of the TM velocities associated with the LT and FBLC.
      Runners attained significantly higher TM velocities, greater VO2, greater VE,
      greater heart rate, and a lower ventilatory equivalent for oxygen (VE/VO2) at
      each exercise intensity, with the exceptions of heart rate at 4.0 mM and VE/VO2
      at the LT. Compared to nonrunners, runners also attained higher VO2, VE, and
      heart rate relative to peak values at LT and 2.0, 2.5, and 4.0 mM. Despite these
      relative and absolute physiological differences, there were no differences
      between groups in local, central, or overall ratings of perceived exertion (RPE)
      (Borg scale) at any condition. The data from both groups were combined to give
      the following means and SD for overall RPE during horizontal running: at the LT
      11.0 +/- 2.0, and at FBLC of 2.0 mM-13.7 +/- 2.1, 2.5 mM-14.5 +/- 1.8, and 4.0 mM
      16.5 +/- 2.3.

PMID- 1997817
TI  - Effect of exercise modality on ratings of perceived exertion at various lactate
      concentrations.
AB  - The effect of exercise modality on the relationship between ratings of perceived
      exertion (RPE), blood lactate concentration, oxygen uptake (VO2), and heart rate
      (HR) was examined in 29 untrained male subjects who completed counterbalanced
      VO2max/lactate threshold (LT) protocols on a cycle ergometer (CE) and treadmill
      (TM). Heart rate, VO2, and RPE were determined at power outputs corresponding to
      LT and fixed blood lactate concentrations (FBLC) of 2.0, 2.5, and 4.0 mM and
      during maximal exercise. A repeated measures ANOVA indicated that, despite
      significant differences across exercise modality in HR and VO2 at LT, FBLC, and
      maximal exercise, no significant differences in RPE were found between exercise
      modalities during leg exercise. Mean (+/- SD) respective values for overall RPE
      at LT and FBLC of 2.0 mM, 2.5 mM, 4.0 mM, and max were 10.2 (2.2), 13.1 (2.1),
      14.1 (2.3), 15.9 (2.3), and 18.8 (1.3) for the CE and 10.8 (1.9), 13.8 (1.8),
      14.6 (1.6), 16.2 (2.6), and 18.5 (1.5) for the TM. It was concluded that exercise
      modality does not affect the perception of exertion at LT, FBLC, or maximal
      exercise and that a strong relationship exists between RPE and blood lactate
      concentrations.

PMID- 1997819
TI  - Governor Engler and health care.

PMID- 1997818
TI  - Physiological and biomechanical factors associated with elite endurance cycling
      performance.
AB  - In this study we evaluated the physiological and biomechanical responses of
      "elite-national class" (i.e., group 1; N = 9) and "good-state class" (i.e., group
      2; N = 6) cyclists while they simulated a 40 km time-trial in the laboratory by
      cycling on an ergometer for 1 h at their highest power output. Actual road racing
      40 km time-trial performance was highly correlated with average absolute power
      during the 1 h laboratory performance test (r = -0.88; P less than 0.001). In
      turn, 1 h power output was related to each cyclists' VO2 at the blood lactate
      threshold (r = 0.93; P less than 0.001). Group 1 was not different from group 2
      regarding VO2max (approximately 70 ml.kg-1.min-1 and 5.01 l.min-1) or lean body
      weight. However, group 1 bicycled 40 km on the road 10% faster than group 2 (P
      less than 0.05; 54 vs 60 min). Additionally, group 1 was able to generate 11%
      more power during the 1 h performance test than group 2 (P less than 0.05), and
      they averaged 90 +/- 1% VO2max compared with 86 +/- 2% VO2max in group 2 (P =
      0.06). The higher performance power output of group 1 was produced primarily by
      generating higher peak torques about the center of the crank by applying larger
      vertical forces to the crank arm during the cycling downstroke. Compared with
      group 2, group 1 also produced higher peak torques and vertical forces during the
      downstroke even when cycling at the same absolute work rate as group 2. Factors
      possibly contributing to the ability of group 1 to produce higher "downstroke
      power" are a greater percentage of Type I muscle fibers (P less than 0.05) and a
      23% greater (P less than 0.05) muscle capillary density compared with group 2. We
      have also observed a strong relationship between years of endurance training and
      percent Type I muscle fibers (r = 0.75; P less than 0.001). It appears that
      "elite-national class" cyclists have the ability to generate higher "downstroke
      power", possibly as a result of muscular adaptations stimulated by more years of
      endurance training.

PMID- 1997820
TI  - "The midwife as practitioner." Midwifery standards--uniformity or quality?

PMID- 1997821
TI  - Great expectations.

PMID- 1997823
TI  - Community-oriented medical education: what is it?
AB  - The pressing need for this communication has emerged from the author's experience
      in conducting educational workshops, seminars and meetings for the orientation of
      health professionals in community-oriented medical education. Many questions are
      raised and many statements made which clearly indicate that the term 'community
      oriented medical education' (COME) is still misunderstood. It carries a different
      meaning for different people. Many give it their own meaning and attach to it
      their own interpretations. This has resulted in wide propagation of the wrong
      concepts to the detriment of promoting the approach. (It is worth noting that
      'community medicine' has over the years suffered the same fate. Is it because
      both terms include the word 'community', which often has a poor image for much of
      the medical profession?) An attempt is made here to clarify the situation by a
      process of questions and answers, the questions being those frequently asked as
      such or posed in the form of statements. They are by no means exhaustive. Seven
      major such questions are addressed with reference to personal experience and the
      literature. (1) What do we mean by COME, community-based education (CBE) and
      community-based learning (CBL)? (2) COME is third-grade medical education
      producing third-grade graduates and 'barefoot doctors'. (3) COME produces
      community health doctors/specialists. (4) COME is not scientifically based (based
      only on soft sciences) and basic sciences are neglected. (5) Graduates from COME
      programmes are not competent in dealing with patients as they spend most of their
      time in the community. (6) If it is community-oriented education, then what about
      the hospital?(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1997822
TI  - Familial factors in going to medical school.
AB  - Attending medical school has long been known to be strongly familial. We set out
      to discover whether this tendency has been altered by recent procedures for
      selection of medical students. Preclinical medical students in the University of
      Wales College of Medicine, Cardiff and first-year zoology students completed a
      self-report questionnaire on the frequency of going to medical school among their
      first- and second-degree relatives. Thirteen per cent of the first degree
      relatives of the medical student proband group had attended medical school,
      compared with approximately 0.22% of the general population, giving a 'relative
      risk' of 61. Twenty-one per cent of the siblings over age 18 years of the medical
      student probands had been or were currently in a medical school, compared with 4%
      of the zoology student proband siblings. We conclude that going to medical school
      remains highly familial and this is probably largely determined by
      environmental/cultural and social factors. However, it is possible that genetic
      factors contribute in a non-specific way, e.g. via their influence on general
      intelligence.

PMID- 1997824
TI  - Medical students' reactions to a nursing attachment scheme.
AB  - This paper provides a description of preclinical students' reports after two
      shifts on a nursing attachment scheme. Quotations were taken from short essays
      which were submitted as part of their course work in psychology. The experience
      had clear effects on some students and could have lasting implications for their
      later work as doctors. Themes gathered from essays included aspects of patient
      care (loss of independence, uncertainty, and the effects of the hospital
      structure), the nursing role (especially the surprise at the high level of
      technical skill shown by nursing staff), the doctor's role (particularly the
      importance of the nurse-doctor relationship), and emotional reactions in
      students. The students raised several ethical issues. Although the attachment had
      many positive consequences, including an increase in motivation to continue on
      the medical course and an increased appreciation of the individual needs of
      patients, it did raise issues which the students were unable to deal with or
      analyse adequately. Further support and teaching in particular areas are
      recommended.

PMID- 1997825
TI  - Current practice patterns and training status of selected graduates at the King
      Abdulaziz University College of Medicine, Saudi Arabia.
AB  - Graduate doctors are the primary output of medical education programmes. It is
      important for institutions to identify systematically the types of medical
      activities in which their former students are involved in order to determine the
      effectiveness of the curriculum, assessing academic standards and reviewing
      admissions policies. Information was obtained from a survey of men and women
      graduates from three of the early graduation classes of King Abdulaziz University
      College of Medicine in Saudi Arabia about postgraduate medical training,
      certification, practice patterns, and other curriculum issues. Information
      collected from 151 graduates (90%) indicated that 96% were practising medicine in
      a variety of medical specialties and subspecialties. Six were not practising at
      the time of the study. Significant differences were found in the specialties
      being practised when men and women were compared. Men tended to practise in
      medicine, surgery, dermatology, urology, ENT, ophthalmology and orthopaedics,
      while women concentrated in obstetrics and gynaecology and paediatrics.
      Certification beyond medical school was earned by 49% with no significant
      difference being found comparing men to women. Men earned the majority of their
      postgraduate certifications outside Saudi Arabia while most women earned theirs
      in Saudi Arabia. Graduates indicated that departments in the basic sciences were
      least helpful in preparing them as doctors, while selected clinical departments
      were most helpful. It was concluded from the study that the curriculum goals of
      the College of Medicine, namely a curriculum of international standards producing
      graduates to take leadership roles in both teaching and medical practice, were
      realized in part by the graduates surveyed.

PMID- 1997826
TI  - Medical students' attitudes towards ageing and death: a cross-sequential study.
AB  - This study presents an analysis of possible changes in attitudes towards older
      persons and in attitudes towards personal death anxiety that might occur over the
      course of undergraduate medical education. Three entering classes of medical
      students at a university in the Mid-western United States completed an attitudes
      towards old people scale, a death anxiety scale, and a standard personality
      inventory. As graduating seniors, they again completed the attitudes towards old
      people scale and the death anxiety scale. Significant changes did not occur. In
      comparison with baseline data from a group of 212 university graduate students in
      the USA, these 234 medical undergraduates had significantly more positive
      attitudes towards the aged; in another comparison, their death anxiety was
      significantly lower than a group of 599 from the general population. Implications
      are discussed.

PMID- 1997827
TI  - Assessment of emergency medicine: a comparison of an experimental objective
      structured clinical examination with a practical examination.
AB  - An emergency medicine and trauma programme was implemented at Ben Gurion
      University Medical School in Israel. Clinical performance assessment of the first
      year course in emergency medicine and trauma was done using a practical
      examination (PE). In the continuous process of critically reviewing the course
      objectives and assessment methods the objective structured clinical examination
      (OSCE) was chosen, for the first time in our medical school, as a tool for course
      development as well as evaluation of the existing PE. Seven experimental OSCE
      stations were designed which covered some of the course and practical examination
      topics. Twenty-six first-year medical students have taken both examinations
      concurrently. Twenty-three students answered an attitude questionnaire regarding
      both examinations. Results have indicated that the OSCE provided additional and
      crucial information on students' deficiencies in clinical performance which were
      not available from the PE. Those differences were probably due to realistic OSCE
      station content, highly simulated set-ups, and the objectivity of the examiner,
      all of which have contributed to a more challenging examination, as compared to
      the PE. The OSCE in emergency medicine and trauma seemed to have a relatively
      high level of acceptance by both staff and students. In our opinion it seems that
      the OSCE is a better tool for first-year level final assessment in emergency
      medicine and trauma. is a better tool for first-year level final assessment

PMID- 1997828
TI  - The objective structured clinical examination in undergraduate psychiatry.
AB  - Inadequate attention has been given to verifying the psychometric attributes of
      the objective structured clinical examination (OSCE), yet its popularity has been
      increasing in recent years. Our 6 years' experience in Nigeria showed that OSCE
      is practicable in undergraduate psychiatry assessment and there is evidence over
      consecutive years that it has satisfactory reliability and criterion-based
      validity. The importance of students' feedback in assessing the quality of
      examination is reinforced, and subtle, less tangible elements which determine
      students' performance, such as social interactional mystique and some personality
      traits, are worthy of evaluative research.

PMID- 1997829
TI  - The pre-registration house officer year: a critical incident study.
AB  - To define the major problems faced by pre-registration house officers, 328
      critical incidents from 200 house officers and related staff were collected. Each
      incident was analysed and key words representing the main features were
      abstracted. These were then aggregated into eight broad categories; personal
      aspects, clinical skills, communication and relationships, problem-related,
      organization skills, education, dying patients, and administration. Further
      analysis of the incidents suggested a series of conclusions which include the
      need for effective supervision of the house officer with feedback on performance.
      An induction/orientation period is necessary; there is evidence that a proportion
      of house officers need additional experience of practical procedures; house
      officers often have difficulty in setting priorities and they have little
      experience, prior to qualification, of organizational skills; during the year
      they are very busy with little time off. Facilities and accommodation may be less
      than adequate. They perceive a lack of support from senior staff to help with
      personal problems and career guidance; they are conscious that communication
      skills are of great importance and would like additional help with this; there is
      little time for formal education during the year. The range of clinical material
      presented is enormous, however, and the challenge for medical education is to
      ensure that the opportunities for learning are not missed.

PMID- 1997830
TI  - Advanced training in general practice in the UK for overseas postgraduates.
AB  - The strengths of general practice in the UK as a training environment for
      overseas doctors intending to implement the World Health Organization strategy
      'Health for All by the Year 2000' in primary care are identified. A course of
      advanced training for teachers and administrators of primary care is described
      and evaluated in terms of participants' academic achievements and wider issues,
      including influence upon the development of primary care in their countries of
      origin.

PMID- 1997831
TI  - 'Shadowing' a manager: an exercise in senior registrar management training.
AB  - A senior registrar 'shadowed' a district general manager and a unit general
      manager for one week each as a management training exercise. The three principal
      participants describe the exercise from their different perspectives. Consequent
      issues and the value of such 'shadowing' as a mode of training are discussed.

PMID- 1997832
TI  - Medical education and the corresponding professional needs of young doctors: the
      Finnish Junior Physician 88 study.
AB  - The Universities of Kuopio and Tampere in collaboration with the Ministry of
      Social Affairs and Health and Finnish Medical Association carried out the 'Junior
      Physician 88' study in 1988, the purpose of which was to shed further light on
      the life situation and future plans of young doctors and their views concerning
      undergraduate and postgraduate medical education. The study concerned all the
      doctors registered during the years 1977-1986 in Finland (n = 5208). After
      randomization, a postal questionnaire was sent to one half (n = 2631) of these
      doctors. After the first reminder letter, 1745 questionnaires (66.3%) were
      returned. According to the views of the respondents undergraduate hospital
      teaching was adequate but the teaching of practice in health centres, school
      health care, team-work, health care of the elderly, home health care,
      rehabilitation, environmental health care and administration did not meet the
      professional needs of doctors. All doctors were satisfied with the hospital
      teaching in their undergraduate curriculum. However, only the doctors who
      graduated from the two modern universities in Kuopio and Tampere were satisfied
      with their undergraduate health centre teaching.

PMID- 1997833
TI  - Paralytic shellfish poisoning--Massachusetts and Alaska, 1990.
AB  - Paralytic shellfish poisoning (PSP) is a foodborne illness caused by consumption
      of shellfish or broth from cooked shellfish that contain either concentrated
      saxitoxin, an alkaloid neurotoxin, or related compounds. This report summarizes
      outbreaks of PSP that occurred in Massachusetts and Alaska in June 1990.

PMID- 1997834
TI  - Cyanide poisonings associated with over-the-counter medication--Washington State,
      1991.
AB  - On February 2, 9, and 17, 1991, three persons in western Washington state, who
      had taken SUDAFED 12-Hour capsules (manufactured by Burroughs Wellcome Company)
      for nasal congestion, had onset of acute cyanide poisoning; two died. This report
      updates an ongoing investigation by the Food and Drug Administration (FDA) and
      other agencies.

PMID- 1997835
TI  - Effective surgical adjuvant therapy for high-risk rectal carcinoma.
AB  - BACKGROUND: Radiation therapy as an adjunct to surgery for rectal cancer has been
      shown to reduce local recurrence but has not improved survival. In a previous
      study, combined radiation and chemotherapy improved survival significantly as
      compared with surgery alone, but not as compared with adjuvant radiation, which
      many regard as standard therapy. We designed a combination regimen to optimize
      the contribution of chemotherapy, decrease recurrence, and improve survival as
      compared with adjuvant radiation alone. METHODS: Two hundred four patients with
      rectal carcinoma that was either deeply invasive or metastatic to regional lymph
      nodes were randomly assigned to postoperative radiation alone (4500 to 5040 cGy)
      or to radiation plus fluorouracil, which was both preceded and followed by a
      cycle of systemic therapy with fluorouracil plus semustine (methyl-CCNU).
      RESULTS: After a median follow-up of more than seven years, the combined therapy
      had reduced the recurrence of rectal cancer by 34 percent (P = 0.0016; 95 percent
      confidence interval, 12 to 50 percent). Initial local recurrence was reduced by
      46 percent (P = 0.036; 95 percent confidence interval, 2 to 70 percent), and
      distant metastasis by 37 percent (P = 0.011; 95 percent confidence interval, 9 to
      57 percent). In addition, combined therapy reduced the rate of cancer-related
      deaths by 36 percent (P = 0.0071; 95 percent confidence interval, 14 to 53
      percent) and the overall death rate by 29 percent (P = 0.025; 95 percent
      confidence interval, 7 to 45 percent). Its acute toxic effects included nausea,
      vomiting, diarrhea, leukopenia, and thrombocytopenia. These effects were seldom
      severe. Severe, delayed treatment-related reactions, usually small-bowel
      obstruction requiring surgery, occurred in 6.7 percent of all patients receiving
      radiation, and the frequencies of these complications were comparable in both
      treatment groups. CONCLUSIONS: The combination of postoperative local therapy
      with radiation plus fluorouracil and systemic therapy with a fluorouracil-based
      regimen significantly and substantively improves the results of therapy for
      rectal carcinoma with a poor prognosis, as compared with postoperative radiation
      alone.

PMID- 1997836
TI  - Evidence that histamine is the causative toxin of scombroid-fish poisoning.
AB  - BACKGROUND: The highest morbidity worldwide from fish poisoning results from the
      ingestion of spoiled scombroid fish, such as tuna and mackerel, and its cause is
      not clear. Histamine could be responsible, because spoiled scombroid fish contain
      large quantities of histamine. Whether histamine is the causative toxin, however,
      has remained in question. To address this issue, we investigated whether
      histamine homeostasis is altered in poisoned people. METHODS: The urinary
      excretion of histamine and its metabolite, N-methylhistamine, was measured in
      three persons who had scombroid-fish poisoning (scombrotoxism) after the
      ingestion of marlin. We measured 9 alpha, 11 beta-dihydroxy-15-oxo-2,3,18,19
      tetranorprost-5-ene-1,20-dioic acid (PGD-M), the principal metabolite of
      prostaglandin D2, a mast-cell secretory product, to assess whether mast cells had
      been activated to release histamine. RESULTS: The fish contained high levels of
      histamine (842 to 2503 mumol per 100 g of tissue). Symptoms of scombrotoxism-
      flushing and headache--began 10 to 30 minutes after the ingestion of fish. In
      urine samples collected one to four hours after fish ingestion, the levels of
      histamine and N-methylhistamine were 9 to 20 times and 15 to 20 times the normal
      mean, respectively. During the subsequent 24 hours, the levels fell to 4 to 15
      times and 4 to 11 times the normal values. Levels of both were normal 14 days
      later. PGD-M excretion was not increased at any time. Two persons treated with
      diphenhydramine had prompt amelioration of symptoms. CONCLUSIONS: Scombroid-fish
      poisoning is associated with urinary excretion of histamine in quantities far
      exceeding those required to produce toxicity. The histamine is most likely
      derived from the spoiled fish. These results identify histamine as the toxin
      responsible for scombroid-fish poisoning.

PMID- 1997837
TI  - Transient hypoparathyroidism during acute alcohol intoxication.
AB  - BACKGROUND: Persons with chronic alcoholism frequently have hypocalcemia,
      hypomagnesemia, and osteoporosis. The short-term effects of alcohol ingestion on
      calcium and magnesium metabolism are poorly understood, however. METHODS: We
      measured serum calcium, magnesium, and phosphate concentrations in 17 normal men
      and 7 normal women before and at intervals up to 16 hours after the ingestion of
      1.2 to 1.5 g of alcohol per kilogram of body weight over a 3-hour period (doses
      sufficient to cause acute intoxication). Urinary excretion of calcium, magnesium,
      and phosphate and serum calciotropic hormone levels were measured in 16 of these
      subjects. As a control, the same measurements were made after the ingestion of
      fruit juice instead of alcohol. RESULTS: The mean (+/- SE) peak blood alcohol
      level in the men was 37.5 +/- 1.6 mmol per liter, and in the women it was 38.0 +/
      3.2 mmol per liter. In the men the mean serum parathyroid hormone concentration
      decreased from 16.1 +/- 2.1 to 6.8 +/- 0.9 ng per liter at the end of the three
      hour drinking period. The value at this time was 30 percent of that at the end of
      the three-hour session during which the men drank fruit juice (P = 0.004). The
      serum concentration of ionized calcium reached a nadir eight hours after the
      beginning of alcohol administration (decreasing from 1.18 +/- 0.01 to 1.15 +/-
      0.01 mmol per liter; P less than 0.001 as compared with values during the fruit
      juice study), and urinary excretion of calcium increased from 0.34 +/- 0.08 to
      0.36 +/- 0.08 mmol per hour (P less than 0.01 as compared with values during the
      fruit-juice study). Serum parathyroid hormone levels exceeded base-line values
      during the last 4 hours of the 16-hour study period; this increase was
      accompanied by a decrease in the urinary excretion of calcium. Both serum levels
      of magnesium (in the first 6 hours) and urinary levels (in the first 12 hours)
      increased after the ingestion of alcohol. In the women, serum parathyroid hormone
      levels decreased from 29.2 +/- 2.8 to 17.3 +/- 2.6 ng per liter two hours after
      the administration of alcohol was begun (P less than 0.001) and increased above
      base-line values during the last four hours of the study period. The serum
      concentration of ionized calcium decreased from 1.20 +/- 0.01 to 1.16 +/- 0.01
      mmol per liter, reaching a nadir 8 to 12 hours after alcohol administration was
      begun (P less than 0.001). CONCLUSIONS: Short-term alcohol administration causes
      transitory hypoparathyroidism. This decline in the secretion of parathyroid
      hormone accounts at least in part for the transient hypocalcemia, hypercalciuria,
      and hypermagnesuria that follow alcohol ingestion.

PMID- 1997838
TI  - Video display terminals and the risk of spontaneous abortion.
AB  - BACKGROUND: The relation between spontaneous abortion and the use of video
      display terminals (VDTs) is of great public health concern. Previous
      investigators of this issue have reported inconsistent findings. METHODS: To
      determine whether electromagnetic fields emitted by VDTs are associated with an
      increased risk of spontaneous abortion, a cohort of female telephone operators
      who used VDTs at work was compared with a cohort of operators who did not use
      VDTs. To obtain reliable estimates of exposure, we determined the number of hours
      of VDT use per week from company records and measured electromagnetic fields at
      VDT workstations and, for purposes of comparison, at workstations without VDTs.
      Operators who used VDTs had higher abdominal exposure to very-low-frequency (15
      kHz) electromagnetic fields (workstations without VDTs did not emit very-low
      frequency energy). Abdominal exposure to extremely-low-frequency fields (45 to 60
      Hz) was similar for both operators who used VDTs and those who did not. Among
      2430 women interviewed, there were 882 pregnancies that met our criteria for
      inclusion in the study. RESULTS: We found no excess risk of spontaneous abortion
      among women who used VDTs during the first trimester of pregnancy (odds ratio =
      0.93; 95 percent confidence interval, 0.63 to 1.38), and no dose-response
      relation was apparent when we examined the women's hours of VDT use per week
      (odds ratio for 1 to 25 hours per week = 1.04; 95 percent confidence interval,
      0.61 to 1.79; odds ratio for greater than 25 hours per week = 1.00; 95 percent
      confidence interval, 0.61 to 1.64). There continued to be no risk associated with
      the use of VDTs when we accounted for multiple pregnancies, conducted separate
      analyses of early abortion, late abortion, and all fetal losses, or limited our
      analyses to spontaneous abortions for which a physician was consulted.
      CONCLUSIONS: The use of VDTs and exposure to the accompanying electromagnetic
      fields were not associated with an increased risk of spontaneous abortion in this
      study.

PMID- 1997839
TI  - Racial differences in the relation between blood pressure and insulin resistance.
AB  - BACKGROUND: Insulin resistance and the concomitant compensatory hyperinsulinemia
      have been implicated in the pathogenesis of hypertension. However, reports on the
      relation between insulin and blood pressure are inconsistent. This study was
      designed to investigate the possibility of racial differences in this relation.
      METHODS: We studied 116 Pima Indians, 53 whites, and 42 blacks who were
      normotensive and did not have diabetes; the groups were comparable with respect
      to mean age (29, 30, and 31 years, respectively) and blood pressure (113/70,
      111/68, and 113/68 mm Hg, respectively). Insulin resistance was determined by the
      euglycemic-hyperinsulinemic clamp technique during low-dose (40 mU per square
      meter of body-surface area per minute) and high-dose (400 mU per square meter per
      minute) insulin infusions. RESULTS: The Pima Indians had higher fasting plasma
      insulin concentrations than the whites or blacks (176, 138, and 122 pmol per
      liter, respectively; P = 0.002) and lower rates of whole-body glucose disposal
      during both the low-dose (12.7, 17.1, and 19.5 mmol per minute; P less than
      0.001) and the high-dose (38.0, 43.1, and 45.7 mmol per minute; P less than
      0.001) insulin infusions. After adjustment for age, sex, body weight, and
      percentage of body fat, mean blood pressure (calculated as 1/3 systolic pressure
      + 2/3 diastolic pressure) was significantly correlated with the fasting plasma
      insulin concentration (r = 0.42) and the rate of glucose disposal during the low
      dose (r = -0.41) and high-dose (r = -0.49) insulin infusions (P less than 0.01
      for each) in whites, but not in Pima Indians (r = -0.06, -0.02, and -0.04,
      respectively) or blacks (r = -0.10, -0.04, and 0.02, respectively). CONCLUSIONS:
      The relations between insulinemia, insulin resistance, and blood pressure differ
      among racial groups and may be mediated by mechanisms active in whites, but not
      in Pima Indians or blacks.

PMID- 1997840
TI  - Smoking cessation and severity of weight gain in a national cohort.
AB  - BACKGROUND: Many believe that the prospect of weight gain discourages smokers
      from quitting. Accurate estimates of the weight gain related to the cessation of
      smoking in the general population are not available, however. METHODS: We related
      changes in body weight to changes in smoking status in adults 25 to 74 years of
      age who were weighed in the First National Health and Nutrition Examination
      Survey (NHANES I, 1971 to 1975) and then weighed a second time in the NHANES I
      Epidemiologic Follow-up Study (1982 to 1984). The cohort included continuing
      smokers (748 men and 1137 women) and those who had quit smoking for a year or
      more (409 men and 359 women). RESULTS: The mean weight gain attributable to the
      cessation of smoking, as adjusted for age, race, level of education, alcohol use,
      illnesses related to change in weight, base-line weight, and physical activity,
      was 2.8 kg in men and 3.8 kg in women. Major weight gain (greater than 13 kg)
      occurred in 9.8 percent of the men and 13.4 percent of the women who quit
      smoking. The relative risk of major weight gain in those who quit smoking (as
      compared with those who continued to smoke) was 8.1 (95 percent confidence
      interval, 4.4 to 14.9) in men and 5.8 (95 percent confidence interval, 3.7 to
      9.1) in women, and it remained high regardless of the duration of cessation. For
      both sexes, blacks, people under the age of 55, and people who smoked 15
      cigarettes or more per day were at higher risk of major weight gain after
      quitting smoking. Although at base line the smokers weighed less than those who
      had never smoked, they weighed nearly the same at follow-up. CONCLUSIONS: Major
      weight gain is strongly related to smoking cessation, but it occurs in only a
      minority of those who stop smoking. Weight gain is not likely to negate the
      health benefits of smoking cessation, but its cosmetic effects may interfere with
      attempts to quit. Effective methods of weight control are therefore needed for
      smokers trying to quit.

PMID- 1997841
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 11-1991. A 65-year-old man with a vertebral and disk lesion after
      a pulmonary operation for Aspergillus infection.

PMID- 1997842
TI  - Combined-modality therapy for rectal carcinoma--the time has come.

PMID- 1997843
TI  - Scombroid-fish poisoning. From pathogenesis to prevention.

PMID- 1997844
TI  - Smoking cessation and weight gain.

PMID- 1997845
TI  - Detection of minimal residual disease in childhood leukemia with the polymerase
      chain reaction.

PMID- 1997846
TI  - Adjuvant therapy in epithelial ovarian cancer.

PMID- 1997847
TI  - The renin-angiotensin system and polycystic kidney disease.

PMID- 1997848
TI  - Topical capsaicin in the treatment of painful diabetic neuropathy.

PMID- 1997849
TI  - Anaphylaxis from a tick bite.

PMID- 1997850
TI  - Effect of a short course of prednisone in the prevention of early relapse after
      the emergency room treatment of acute asthma.
AB  - BACKGROUND: Relapse after the treatment of acute asthma in the emergency room is
      common (occurring in 25 to 30 percent of cases) and is not accurately predicted
      by any available measurements. We studied the usefulness of prednisone in
      reducing this high rate of relapse. METHODS: One hundred twenty-two patients
      treated in the emergency room for acute exacerbations of asthma were assigned in
      a randomized, double-blind fashion to receive at discharge either prednisone for
      eight days (the dose being tapered from 40 to 0 mg per day) or matching placebo.
      Ninety-three were subsequently discharged from the emergency room and
      participated in the trial. On days 1, 7, and 14 after discharge, the patients
      were assessed during home visits with spirometry and diary-card review; they were
      contacted by telephone on day 21. Relapse was defined as an unscheduled medical
      visit occasioned by the patient's perceived need for further asthma treatment.
      RESULTS: The overall risk of relapse was significantly lower in the prednisone
      group (P less than 0.05), with a significantly reduced rate of relapse during the
      first 10 days of follow-up (3 of 48, as compared with 11 of 45 in the placebo
      group; P less than 0.05). Thereafter (days 11 through 21), there was no further
      significant difference in relapse rates between treatment groups (five in the
      prednisone group and six in the placebo group). During the first week after
      discharge, patients receiving prednisone reported significantly lower mean (+/-
      SD) daily symptom scores for shortness of breath (1.4 +/- 0.4 vs. 2.5 +/- 0.4, P
      less than 0.01) and less frequent use of an inhaled bronchodilator (5.2 +/- 0.5
      vs. 6.9 +/- 0.2 puffs per day, P less than 0.05) than patients receiving placebo.
      Subsequently, symptom scores and bronchodilator use were similar in the two
      groups. CONCLUSIONS: A short course of prednisone reduced early relapse rates
      after the treatment of acute asthma in the emergency room, an effect limited to
      the period of steroid administration.

PMID- 1997851
TI  - Improvement in the diagnosis of abscesses associated with endocarditis by
      transesophageal echocardiography.
AB  - BACKGROUND: Echocardiography is recognized as the method of choice for the
      noninvasive detection of valvular vegetations in patients with infective
      endocarditis, with transesophageal echocardiography being more accurate than
      transthoracic echocardiography. The diagnosis of associated abscesses by
      transthoracic echocardiography is difficult or even impossible in many cases,
      however, and it is not known whether transesophageal echocardiography is any
      better. METHODS: To determine the value of transesophageal echocardiography in
      the detection of abscesses associated with endocarditis, we studied prospectively
      by two-dimensional transthoracic and transesophageal echocardiography 118
      consecutive patients with infective endocarditis of 137 native or prosthetic
      valves that was documented during surgery or at autopsy. RESULTS: During surgery
      or at autopsy, 44 patients (37.3 percent) had a total of 46 definite regions of
      abscess. Abscesses were more frequent in aortic-valve endocarditis than in
      infections of other valves, and the infecting organism was more often
      staphylococcus (52.3 percent of cases) in patients with abscesses than in those
      without abscesses (16.2 percent). The hospital mortality rate was 22.7 percent in
      patients with abscesses, as compared with 13.5 percent in patients without
      abscesses. Whereas transthoracic echocardiography identified only 13 of the 46
      areas of abscess, the transesophageal approach allowed the detection of 40
      regions (P less than 0.001). Sensitivity and specificity for the detection of
      abscesses associated with endocarditis were 28.3 and 98.6 percent, respectively,
      for transthoracic echocardiography and 87.0 and 94.6 percent for transesophageal
      echocardiography; positive and negative predictive values were 92.9 and 68.9
      percent, respectively, for the transthoracic approach and 90.9 and 92.1 percent
      for the transesophageal approach. Variation between observers was 3.4 percent for
      transthoracic and 4.2 percent for transesophageal echocardiography. CONCLUSIONS:
      The data indicate that transesophageal echocardiography leads to a significant
      improvement in the diagnosis of abscesses associated with endocarditis. The
      technique facilitates the identification of patients with endocarditis who have
      an increased risk of death and permits earlier treatment.

PMID- 1997852
TI  - Clinical importance of myeloid-antigen expression in acute lymphoblastic leukemia
      of childhood.
AB  - BACKGROUND: Leukemic cells in 15 to 25 percent of patients with acute
      lymphoblastic leukemia (ALL) express myeloid antigens as well as lymphoid
      antigens (the latter reflecting B-cell or T-cell lineage). The relations of
      myeloid-antigen expression to other features of ALL and to prognosis have been
      controversial. METHODS: We analyzed clinical and laboratory features present at
      diagnosis in 236 consecutive cases of ALL in children. Immunophenotyping,
      including single- and dual-fluorescence analyses, was used to classify leukemic
      cells as B or T lymphoblasts and also to identify myeloid-antigen expression--the
      simultaneous expression of lymphoid-associated antigens and at least one of three
      myeloid-associated antigens (CD33, CD13, and CD14) on cells classified as L1 or
      L2 according to the French-American-British system. RESULTS: Forty-five of 185
      patients with B-lineage ALL had myeloid-antigen expression, as did 8 of 41
      patients with T-lineage ALL. In 10 patients, the lineage could not be determined.
      Myeloid-antigen expression was associated with L2 morphology (P less than 0.05),
      but it did not correlate with other prognostic features recognized previously.
      Multivariate analysis showed that myeloid-antigen expression was an important
      predictor of relapse in childhood ALL and the most significant prognostic factor
      statistically (P less than 0.0001). A white-cell count greater than or equal to
      50 x 10(9) per liter at diagnosis was also an important and highly significant
      prognostic feature (P less than 0.001). After 40 months, the estimated disease
      free survival for patients with ALL was 84 percent for those without myeloid
      antigen expression and with a low white-cell count, 57 percent for those without
      myeloid-antigen expression and with a high white-cell count, 47 percent for those
      with myeloid-antigen expression and a low white-cell count, and 26 percent for
      those with myeloid-antigen expression and a high white-cell count (P less than
      0.00001). CONCLUSIONS: Myeloid-antigen expression is an important independent
      predictor of a poor response to chemotherapy in childhood ALL.

PMID- 1997853
TI  - Late cardiac effects of doxorubicin therapy for acute lymphoblastic leukemia in
      childhood.
AB  - BACKGROUND: Cardiotoxicity is a recognized complication of doxorubicin therapy,
      but the long-term effects of doxorubicin are not well documented. We therefore
      assessed the cardiac status of 115 children who had been treated for acute
      lymphoblastic leukemia with doxorubicin 1 to 15 years earlier in whom the disease
      was in continuous remission. METHODS: Eighteen patients received one dose of
      doxorubicin (45 mg per square meter of body-surface area), and 97 received
      multiple doses totaling 228 to 550 mg per square meter (median, 360). The median
      interval between the end of treatment and the cardiac evaluation was 6.4 years.
      Our evaluation consisted of a history, 24-hour ambulatory electrocardiographic
      recording, exercise testing, and echocardiography. RESULTS: Fifty-seven percent
      of the patients had abnormalities of left ventricular afterload (measured as end
      systolic wall stress) or contractility (measured as the stress-velocity index).
      The cumulative dose of doxorubicin was the most significant predictor of abnormal
      cardiac function (P less than 0.002). Seventeen percent of patients who received
      one dose of doxorubicin had slightly elevated age-adjusted afterload, and none
      had decreased contractility. In contrast, 65 percent of patients who received at
      least 228 mg of doxorubicin per square meter had increased afterload (59 percent
      of patients), decreased contractility (23 percent), or both. Increased afterload
      was due to reduced ventricular wall thickness, not to hypertension or ventricular
      dilatation. In multivariate analyses restricted to patients who received at least
      228 mg of doxorubicin per square meter, the only significant predictive factors
      were a higher cumulative dose (P = 0.01), which predicted decreased
      contractility, and an age of less than four years at treatment (P = 0.003), which
      predicted increased afterload. Afterload increased progressively in 24 of 34
      patients evaluated serially (71 percent). Reported symptoms correlated poorly
      with indexes of exercise tolerance or ventricular function. Eleven patients had
      congestive heart failure within one year of treatment with doxorubicin; five of
      them had recurrent heart failure 3.7 to 10.3 years after completing doxorubicin
      treatment, and two required heart transplantation. No patient had late heart
      failure as a new event. CONCLUSIONS: Doxorubicin therapy in childhood impairs
      myocardial growth in a dose-related fashion and results in a progressive increase
      in left ventricular afterload sometimes accompanied by reduced contractility. We
      hypothesize that the loss of myocytes during doxorubicin therapy in childhood
      might result in inadequate left ventricular mass and clinically important heart
      disease in later years.

PMID- 1997854
TI  - Disaster planning and response.

PMID- 1997855
TI  - Diagnosis and management of hormone-secreting pituitary adenomas.

PMID- 1997856
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 12-1991. A 67-year-old man with a ventricular septal defect and
      progressive dyspnea.

PMID- 1997857
TI  - Transesophageal echocardiography--sound diagnostic technique or two-edged sword?

PMID- 1997858
TI  - Doxorubicin-induced cardiac toxicity.

PMID- 1997859
TI  - AIDS in Africa.

PMID- 1997860
TI  - Extracorporeal membrane oxygenation in neonates.

PMID- 1997861
TI  - Long-term continuity of bone cortical area.

PMID- 1997862
TI  - Nephrogenic diabetes insipidus responsive to indomethacin plus dDAVP.

PMID- 1997863
TI  - Mercury exposure from interior latex paint.

PMID- 1997865
TI  - Medical support for American troops in the Persian Gulf.

PMID- 1997864
TI  - Lambada fracture.

PMID- 1997866
TI  - The threat of infectious disease in Americans returning from Operation Desert
      Storm.

PMID- 1997867
TI  - When Congress practices medicine or, where did pete and his colleagues get their
      medical degrees?

PMID- 1997868
TI  - A message to the U.S. health care system: listen to your doctor!

PMID- 1997869
TI  - Criteria screens: administrators can benefit from the results.

PMID- 1997870
TI  - Criteria screens: the most efficient, effective means of measuring quality care?

PMID- 1997871
TI  - ESRD health care screens spell increasing regulation for dialysis facilities.

PMID- 1997872
TI  - Measuring quality care in hemodialysis.

PMID- 1997873
TI  - More regulation, but screens can have some benefit.

PMID- 1997874
TI  - "Drug costs".

PMID- 1997875
TI  - A medical point of view: an answer to a medical student's inquiry.

PMID- 1997876
TI  - Amniotic fluid volume assessment: oligohydramnios.

PMID- 1997877
TI  - Cardiac transplantation--first year experience in a community hospital: a three
      year follow-up.
AB  - This is a report of ten consecutive patients with end-stage cardiac disease
      treated with orthotopic cardiac transplantation in a community hospital, during
      the first year of its heart transplantation program. All patients were followed
      for a minimum of 33 months and a maximum of 45 months with 100% survival at two
      years and 90% at three years. All survivors are presently in N.Y.H.A. Class I or
      II. The entire group of patients received the same triple immunosuppressive
      therapy. The incidence of infection and rejection during the first three months
      post-transplantation was 0.3 and 0.6 episodes per patient respectively. Every
      patient developed some degree of deterioration in renal function and 80% of the
      patients now receive treatment for systemic hypertension. The in-hospital
      institution cost for the transplant admission varied from $25,084 to $74,164. To
      date, 30 patients have undergone heart transplantation in our program and 26 are
      long-term successes. This study again proves that renal insufficiency and
      hypertension remain the major side effects of Cyclosporine therapy. We further
      conclude from our experience that cardiac transplantation can be successfully and
      cost effectively performed in a community hospital even with a somewhat lower
      caseload.

PMID- 1997878
TI  - Sinemet CR in Parkinson's disease.
AB  - Sinemet CR, a controlled release carbidopa/levodopa preparation, was compared to
      conventional carbidopa/levodopa in a double blind, placebo-controlled trial.
      Comparable clinical benefits and adverse effects were noted with the two
      medications. However significantly less frequent dosing was necessary with
      Sinemet CR.

PMID- 1997879
TI  - National Rural Health Association.

PMID- 1997880
TI  - ANA releases statement on mobilization of nurses.

PMID- 1997881
TI  - Study on low birthweight infants.

PMID- 1997882
TI  - Budget fat to control cholesterol.

PMID- 1997883
TI  - Ethical decision-making and spirituality.

PMID- 1997884
TI  - Magnetic resonance imaging in the preoperative evaluation of cervical
      radiculopathy.
AB  - Forty patients with cervical radiculopathy were examined preoperatively with
      magnetic resonance imaging (MRI). MRI was used alone in 27 (68%) of the 40
      patients; the remainder also had computed tomography in conjunction with
      myelography. The primary criterion on MRI for a clinically significant lesion was
      asymmetrical narrowing of the subarachnoid space in the region of the nerve root.
      Surgical confirmation of the abnormality was obtained in all 40 cases. The
      operative findings were a herniated nucleus pulposus (32 of 40 patients),
      spondylosis (2 of 40 patients), or a combination of the two (6 of 40 patients).
      MRI identified a surgical lesion (herniated nucleus pulposus, spondylosis, or
      both) in 37 of the 40 (92%) patients. We think MRI is the only preoperative
      imaging examination necessary in most cases of cervical radiculopathy.

PMID- 1997885
TI  - Asymptomatic versus symptomatic herniated thoracic discs: their frequency and
      characteristics as detected by computed tomography after myelography.
AB  - We retrospectively reviewed the myelograms of 433 patients and identified those
      who had no symptoms or signs referable to the thoracic cord, roots, or nerves. By
      post-myelography computed tomographic scan criteria, our frequency of
      asymptomatic thoracic herniated discs (ATHDs) was calculated. Post-myelography
      computed tomographic scans of 68 ATHDs were analyzed. Their imaging
      characteristics were compared with our own series of 5 symptomatic thoracic
      herniated discs and symptomatic thoracic herniated discs in the literature. We
      were unable to identify any imaging features that could reliably classify a disc
      as an ATHD or a symptomatic thoracic herniated disc. Our results call into
      question the propriety of prophylactic surgery for ATHDs, even when the lesions
      are radiographically impressive.

PMID- 1997886
TI  - Intracranial hypertension in relation to memory functioning during the first year
      after severe head injury.
AB  - The relationship between intracranial hypertension and residual memory deficit
      after closed head injury was evaluated using the 6-month and 1-year
      neurobehavioral outcome data obtained by the Traumatic Coma Data Bank.
      Intracranial pressure was analyzed using the percentage of time that it exceeded
      20 mm Hg and the maximum value recorded during the first 72 hours after injury.
      Memory measures included recall of word lists, prose recall, and visual memory
      for designs that were obtained 6 months (n = 149) and 1 year (n = 132) after
      injury. Intracranial hypertension occurred in more than half of the Traumatic
      Coma Data Bank cohort who met the criteria for the neurobehavioral follow-up
      study. Linear regression analysis disclosed an effect of elevated intracranial
      pressure on some, but not all, measures of memory at 6 months, whereas the
      results were negative for the 1-year follow-up examination. We conclude that the
      elevation of intracranial pressure exerts little if any effect on later memory
      functioning, and that any effect it does have diminishes over 1 year in survivors
      of severe head injury.

PMID- 1997887
TI  - Chemotherapy of brain metastases from lung carcinoma: a controlled randomized
      study.
AB  - A controlled randomized study was carried out to evaluate the effects of
      chemotherapy in patients with brain metastases from lung carcinoma. One hundred
      patients were randomly divided into three groups at the time of diagnosis or
      after surgery for metastases. Group A received radiotherapy alone; Group B
      received radiotherapy and chloroethylnitrosoureas (methyl-CCNU, 100-120 mg/m2, or
      ACNU 80-100 mg/m2, every 6-8 weeks), and Group C received radiotherapy and a
      combination of chloroethylnitrosoureas and tegafur (300 mg/m2, daily). Of the 100
      patients, 88 could be evaluated. The reduction rates of the tumors of the
      patients in whom tumor was not surgically removed or not totally removed were
      compared. Complete resolution of the tumor was noted in 29, 69, and 63% of the
      patients in Groups A, B, and C, respectively. Tumor regression of greater than or
      equal to 50% was seen in 36, 69, and 74% of the patients in Groups A, B, and C,
      respectively. The difference in the response rates of Groups A and C was
      statistically significant (P less than 0.05). Median survival after the start of
      treatment for brain metastasis was 27, 30.5, and 29 weeks in Groups A, B and C,
      respectively. There was 1 long-term survivor (more than 5 years) in Group A, 3 in
      Group B, and 1 in Group C. The main cause of death was deterioration attributable
      to the primary lesion or systemic metastasis, and no statistical difference was
      noted in survival time among the groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1997888
TI  - Interstitial irradiation and hyperthermia for the treatment of recurrent
      malignant brain tumors.
AB  - Between June 1987 and June 1989, 29 recurrent malignant gliomas or recurrent
      solitary brain metastases in 28 patients were treated in a Phase I study of
      interstitial irradiation and hyperthermia. Patient age ranged from 18 to 65
      years, and the Karnofsky Performance Status scores ranged from 40 to 90%. There
      were 13 glioblastomas, 10 anaplastic astrocytomas, 3 melanomas, and 3
      adenocarcinomas. Catheters were implanted stereotactically after computed
      tomography-based preplanning. Hyperthermia was administered before and after
      brachytherapy, using one to six 2450- or 915-MHz helical coil microwave antennas
      and one to three multisensor fiberoptic thermometry probes. The goal was to heat
      as much of the tumor as possible to 42.5 degrees C for 30 minutes. Within 30
      minutes after the first hyperthermia treatment, implant catheters were
      afterloaded with high-activity iodine-125 seeds delivering tumor doses of 32.6 to
      61.0 Gy. Most patients had no sensation of heating. Complications included
      seizures in 5 patients, reversible neurological changes in 9 patients, a scalp
      burn in 1, and infections in 3. Of 28 evaluable 2-month follow-up scans, 11
      showed definite improvement in the radiological appearance of the tumor, 4 were
      slightly improved, 7 were stable, and 6 showed tumor progression. Ten patients
      underwent reoperation for persistent tumor and/or necrosis. Eleven of 28 patients
      are alive 40 to 97 weeks after treatment. Thirteen patients died of a brain
      tumor, 2 died of extracranial melanoma metastases, 1 died of new brain melanoma
      metastases, and 1 died of a pulmonary embolus. The median survival was 55 weeks
      overall. Median survival has not yet been reached for the anaplastic astrocytoma
      subgroup. We conclude that interstitial brain hyperthermia using helical coil
      microwave antennas is technically feasible. The level of toxicity is acceptable,
      and the computed tomographic response rate is encouraging.

PMID- 1997889
TI  - Expression of platelet-derived growth factors, transforming growth factors, and
      the ros gene in a variety of primary human brain tumors.
AB  - Ribonucleic acid was isolated from a wide spectrum of central nervous system
      tumors to examine the expression of platelet-derived growth factors (PDGF) A and
      B, tumor growth factors (TGF-beta) 1 and 2, and ros messenger ribonucleic acid.
      Eight glioblastoma cell lines were examined as well as cell cultures from 22
      tumor explants. The explants included 6 glioblastomas, 4 anaplastic astrocytomas,
      5 astrocytomas, 3 ependymal tumors, 2 meningiomas, 1 medulloblastoma. and 1
      ganglioglioma. For comparison, 2 nontumor glial cell cultures were included. The
      PDGF B-chain was expressed in 5 of 8 glioblastoma cell lines, 2 of 6
      glioblastomas, and in 3 of 4 anaplastic astrocytoma explants. There was no PDGF B
      expression in 4 astrocytomas, 3 ependymomas of varying malignancy, in the
      remainder of the tumors, or in the nontumor glial cells. The PDGF A-chain was
      expressed in all of the tumors, with the exception of the malignant ependymoma
      and in both nontumor glial cell cultures. TGF-beta 1 was expressed in all of the
      tumors and in nontumor glial cells. The expression of TGF-beta 2 was expressed in
      many of the benign and malignant tumors and also in both nontumor glial cell
      cultures. The ros messenger ribonucleic acid was expressed in 1 of 5 glioblastoma
      cell lines and in 2 of 6 glioblastoma cell explants, but in none of the other
      tumors or in the nontumor glial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1997890
TI  - Localization of stereotactic targets by microrecordings of thalamic somatosensory
      evoked potentials.
AB  - To improve the localization of stereotactic targets, somatosensory evoked
      potentials (SEPs) were recorded from the thalamus and subthalamic area using a
      specially designed semimicroelectrode in 61 patients and a conventional
      "macroelectrode" in 17 patients. By means of the semimicroelectrode, median nerve
      stimulation evoked two distinct SEPs, consisting of a diphasic wave with a huge
      positivity restricted to the nucleus ventrocaudalis (Vc) and a triphasic wave of
      lower amplitude with a major negativity in the ventral part of the nucleus
      ventrointermedius (Vim) and nucleus ventrooralis posterior (Vop) as well as the
      subthalamic lemniscal pathway. The Vim-Vc junction could thus be clearly
      delineated by an abrupt transition of SEPs from one type to the other with a
      precision of 1 mm. The parvicellular part of the Vc (Vcpc), situated in its basal
      region, was distinguishable from the Vc proper by a significant reduction of the
      positivity elicited by stimulation of the median nerve and by a rapid growth of a
      diphasic SEPs to stimulation of the posterior tibial nerve. In the other thalamic
      nuclei, stimulation of the median nerve elicited triphasic SEPs of a very small
      amplitude, suggesting a volume conduction current from the lemniscal pathway.
      With the macroelectrode, the positivity in the Vc was sensitive to electrode
      manipulation and the thalamic nuclei could not be distinctly outlined. SEP
      monitoring using the semimicroelectrode significantly improved the precision of
      target localization, which allowed minimizing of the volume of the therapeutic
      lesion without losing surgical effectiveness, while avoiding complications
      associated with increased penetration of the coagulating electrode. It is
      suggested that recording serial thalamic SEPs with the semimicroelectrode is a
      practical method to refine stereotactic targets in the thalamus.

PMID- 1997891
TI  - Definition of the role of contemporary surgical management in cisternal and
      parenchymatous cysticercosis cerebri.
AB  - With increasing immigration from endemic regions, the incidence of
      neurocysticercosis in North America is rising. This retrospective study was
      undertaken to examine the role of surgery in those cases presenting with large
      cystic parenchymal and cisternal lesions in the current era of anthelminthic
      agents administered orally. A total of 237 patients presented with newly
      diagnosed neurocysticercosis to our institution over a recent 5-year period (mean
      age, 31.2 years). Among those who presented with cystic mass lesions
      predominantly affecting the brain parenchyma and cisternal spaces, 20 (8.4%; mean
      age, 40.2 years) with large cystic lesions subsequently underwent surgical
      intervention, either because of an emergent presentation or because they were
      refractory to medical management. Clinical presentation included increased
      intracranial pressure, focal neurological deficit, and seizure. Radiographic
      imaging (computed tomography and/or magnetic resonance imaging) demonstrated 12
      cases with cisternal lesions, 7 with parenchymal lesions, and 1 involving both
      compartments. Based on imaging guidelines, 30 operative procedures (excluding
      shunt revisions) were performed (14 craniotomies, 8 cerebrospinal fluid
      diversions, 7 stereotactic procedures, and 1 burr hole drainage). Fifteen (75%)
      showed neurological or symptomatic improvement over a median follow-up period of
      36.4 months. There were three surgery-related complications and no deaths.

PMID- 1997892
TI  - Postoperative computed tomographic evaluation of patients with large pituitary
      tumors treated with operative decompression and radiation therapy.
AB  - Thirty consecutive patients who underwent operative decompression and radiation
      therapy for large sellar and suprasellar pituitary tumors (greater than or equal
      to 2 cm) were studied in terms of the serial computed tomographic (CT) changes.
      There were 23 men and 7 women. The mean age was 49.6 +/- 2.5 years, and the mean
      follow-up was 45.3 +/- 3.9 months. Twenty-eight of the 30 patients had
      transsphenoidal surgery, and 27 had hormonally inactive tumors. Radiation therapy
      was begun within 1 month of surgery with a mean dose of 4855 +/- 70 cGy.
      Postoperative CT scans were obtained within 1 month of surgery and at 6- to 12
      month intervals thereafter. Fourteen patients (45%) had no suprasellar tumor
      visualized in either the early postoperative CT scans or on subsequent scans.
      Eleven patients (35%) had a persistent suprasellar mass during the early
      postoperative period that resolved on serial CT evaluation. The mean time for
      resolution was 10.4 +/- 1.2 months. Six patients (20%) had a persistent
      suprasellar mass on serial CT evaluation. A persistent postoperative mass that
      subsequently resolved in many of the patients was thought to be caused by the
      gradual retraction of the postoperative packing and hematoma, as well as the
      effect of radiation on any residual tumor.

PMID- 1997893
TI  - Cerebrospinal fluid flow dynamics in children with external ventricular drains.
AB  - Fifty-five children had 64 external ventricular drains (EVDs) placed
      predominantly (95%) for cerebrospinal fluid (CSF) shunt infections. In 9
      children, a computer monitoring system measured the CSF output each second
      continuously for up to 24 hours. The monitoring was repeated daily for up to 9
      days. The state of arousal of the patients was recorded simultaneously. In all
      children, daily EVD outputs were related to age, sex, weight, method of
      establishing the EVD, height of the drip chamber, time since insertion, and type
      of infecting organism. Computer monitoring revealed wide fluctuations in flow
      rate, with peak rates frequently greater than 20 ml/h and periods of flow arrest.
      These changes were usually associated with increased arousal, but also occurred
      with sleep. The mean EVD flow rate for all children was 6.3 ml/h. EVD output
      increased with age and weight. EVD output decreased with Gram-negative or
      multiple-organism infections and with elevation of the drip chamber. Resolution
      of the infection, sex of the patient, and method of establishing the EVD had no
      effect on output. These results predict that CSF production increases with brain
      growth in humans: that CSF production is depressed by Gram-negative and multiple
      organism infections: that implanted CSF shunts with standard valves flow at
      equivalent rates to an EVD in the supine position; and that the CSF drainage
      requirements in this group are approximately equal to their EVD outputs.

PMID- 1997894
TI  - An experimental compartmental flow model for assessing the hemodynamic response
      of intracranial arteriovenous malformations to stereotactic radiosurgery.
AB  - Stereotactic radiosurgery has proven to be an effective method of treating
      selected inaccessible or inoperable arteriovenous malformations (AVMs) of the
      brain. Radiation-induced obliteration of successfully-treated AVMs, however,
      occurs only after some latent period after treatment, depending on size,
      location, and dose. An experimental compartmental flow model is proposed to
      describe the hemodynamic alterations in the AVM as a result of the
      pathophysiological changes after radiosurgery, and to analyze temporal
      alterations in AVM blood flow rates and pressure gradients before complete
      obliteration. In representative small (low-flow, 150 ml/min) and large (high
      flow, 440 ml/min) AVMs, it is found that increases in pressure gradients across
      certain vascular structures within the AVM occur during the normal course of
      radiation-induced flow decrease and AVM obliteration. The magnitude of these
      pressure alterations, however, may be within the normal physiological variations
      in cerebrovascular blood pressure. The effects of partial-volume irradiation of
      the AVM is examined by limiting radiosurgical treatment to varying portions of
      the flow compartments within the model. It is found that alterations in pressure
      gradients persist in unirradiated vascular shunts, even after complete
      obliteration of the treated AVM volume. These pressure alterations may increase
      the probability of hemorrhage from the untreated shunts of the AVM and cause
      redistribution of regional cerebral blood flow resulting in increased flow
      through these untreated shunts.

PMID- 1997895
TI  - Percutaneous transvenous catheterization and embolization of vein of galen
      aneurysms.
AB  - Seven cases of vein of Galen aneurysms treated by percutaneous transvenous
      endovascular occlusion of the aneurysmal vein are presented. In one case, the
      approach was via the femoral vein, and in the other six cases, by the jugular
      vein. All of the malformations were multipedicular and, additionally, in six of
      the seven there was an intervening arterial-arterial network between the
      posterior thalamoperforating arteries and the wall of the venous aneurysm. This
      fistulous network was interpreted as purely arterial and not as an associated
      arteriovenous malformation. For this reason, the transvenous approach was
      considered justified, and was performed without risk of hemorrhage caused by
      retrograde venous hypertension. Measurement of intra-aneurysmal pressure during
      the course of treatment allowed better understanding of the hemodynamics of the
      lesions, guided the amount of occlusion to be accomplished during each treatment
      session, and thus may have prevented the phenomenon of normal perfusion pressure
      breakthrough. The percutaneous transvenous approach offers all the advantages of
      the transtorcular approach but avoids surgery. Because of our excellent
      angiographic and clinical results--five complete and two partial occlusions, with
      favorable outcomes and no major complications--we believe that this technique is
      better for the treatment of multipedicular vein of Galen aneurysms than
      transarterial embolization or surgery.

PMID- 1997896
TI  - The influence of the calcium antagonist nimodipine and induced hypertension on
      the behavior of the cerebral pial arteries, the blood-brain barrier, cerebral
      edema, and cerebral infarction in cats with one-hour occlusion of the middle
      cerebral artery.
AB  - Thirty anesthetized cats were randomly assigned to one of three groups of 10 cats
      each: nimodipine treatment, nimodipine treatment combined with induced
      hypertension, or a control group. The behavior of the cerebral pial arteries was
      measured by means of microscopic observation through a cranial window. The middle
      cerebral artery of each cat was clipped for 1 hour via the transorbital approach.
      Five hours after circulation was reestablished in the middle cerebral artery,
      Evans blue dye was injected intravenously: 30 minutes later, the animal was
      killed. Administration of nimodipine or saline in the treated or control group
      was started 5 minutes before the middle cerebral artery was clipped and
      maintained until the end of the experiment. Induced hypertension was produced by
      administration of dopamine during the occlusion. Damage to the blood-brain
      barrier (BBB) was judged by extravasation of Evans blue dye. Cerebral edema and
      infarction were evaluated from histological findings. They were most prominent in
      the control group: the extent of hemisphere affected was as follows (mean +/-
      standard error): extravasation, 40.5 +/- 8.8%; edema, 43.2 +/- 5.7%; infarction,
      35.5 +/- 9.6%. On the other hand, the extravasation of Evans blue dye and
      cerebral edema were significantly more extensive in the group treated with
      nimodipine and induced hypertension (extravasation, 28.2 +/- 9.6% of the
      hemisphere; edema, 30.3 +/- 7.1%) than in the group treated with nimodipine alone
      (extravasation, 18.5 +/- 8.7% of the hemisphere; edema, 19.4 +/- 6.3%), but the
      infarction size was similar in both groups (16.6 +/- 4.9% of the hemisphere in
      the former; 17.0 +/- 6.2 in the latter).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1997897
TI  - Spinal Charcot arthropathy.
AB  - Charcot joints of the spine are well-documented clinical entities most commonly
      associated with tabes dorsalis. Spinal neuropathic joints, however, may be
      produced by other disease processes including syringomyelia. In this review, the
      authors discuss the cause and treatment of spinal Charcot arthropathy with
      emphasis on surgical therapy and results.

PMID- 1997898
TI  - Kenneth McKenzie, Harvey Cushing, and the early neurosurgical treatment of
      spasmodic torticollis.
AB  - In 1923, Dr. Kenneth McKenzie trained at the Peter Bent Brigham Hospital under
      Dr. Harvey Cushing. At that time, a patient with spasmodic torticollis came to
      Cushing and was treated with an innovative operation for this disorder with good
      results. This case sparked an interest in Dr. McKenzie, who published the case 1
      year later. In reviewing the surgical histories from the Peter Bent Brigham
      Hospital, we have found the original records of this well-documented case. The
      record includes postoperative drawings of the intraoperative field by Dr.
      Cushing, a sketch by Dr. McKenzie illustrating the postoperative sensory
      examination, and pre- and postoperative photographs of the patient.

PMID- 1997899
TI  - Emergent aneurysm surgery without cerebral angiography for the comatose patient.
AB  - Neurologically based clinical grading scales offer excellent prognostic
      information for the patient suffering diffuse subarachnoid hemorrhage (SAH).
      These grading scales are less applicable to patients with life-threatening
      intraparenchymal hematomas after aneurysmal rupture. During the last 3 years,
      four patients in a comatose state with brain stem compression syndromes
      documented by computed tomographic scans have undergone emergent operation in our
      neurosurgical service. Each patient was so critically ill that we believed it
      unwise to delay craniotomy for diagnostic angiography. The average delay from the
      onset of coma to skin incision was 3.02 hours (range, 1.67-6.5 hours), and the
      average delay from arrival in our unit until skin incision was 1.8 hours (range,
      0.75-2.5 hours). The condition of two arousable patients deteriorated while they
      were in the emergency room, presumably from new bleeding. Each patient underwent
      craniotomy for hematoma evacuation, definitive aneurysm clipping, and lobectomy
      for decompression. Temporary clipping was employed in one patient, and
      intraoperative rupture occurred in two others. Three patients survived but retain
      significant disability. Emergent craniotomy with empiric exploration of
      appropriate subarachnoid cisterns after hematoma decompression may be life-saving
      in some cases. The delay imposed for diagnostic angiography may be avoided in
      attempts to save vital minutes of severe brain stem compression.

PMID- 1997900
TI  - Isolated trigeminal sensory loss secondary to a distal anterior inferior
      cerebellar artery aneurysm: case report.
AB  - A previously healthy 25-year-old woman suddenly developed right-sided facial
      numbness and a headache. The neurological examination was within normal limits
      with the exception of meningismus and right-sided facial sensory loss. A computed
      tomographic scan and a magnetic resonance imaging study demonstrated an acute
      hematoma in the right cerebellopontine angle. A 4-vessel cerebral angiogram
      revealed no abnormalities. Posterior fossa exploration disclosed a large,
      partially thrombosed, fusiform anterior inferior cerebellar artery aneurysm,
      which indented the pons at the trigeminal root entry zone. The aneurysm was
      excised, and the patient made an excellent recovery. She was left with a
      persistent trigeminal sensory deficit. Anterior inferior cerebellar artery
      aneurysms are rare lesions that generally present with a cerebellopontine angle
      syndrome; occasionally, facial sensory loss is also a feature. Isolated
      trigeminal sensory findings, as illustrated in this case, are extremely unusual
      in posterior fossa vascular lesions.

PMID- 1997901
TI  - Iatrogenic saphenous neuralgia: successful therapy with neuroma resection.
AB  - We report the case of a patient with saphenous neuralgia secondary to iatrogenic
      trauma resulting from bypass surgery in the femoral-popliteal region. Early
      symptoms of this condition were medial calf and ankle pain, with no findings of
      motor and reflex abnormalities. Exploration of the thigh 2 years later revealed a
      neuroma of the nerve in the distal dissection site, medial to the knee. Resection
      of the neuroma alleviated this condition. It is noted that saphenous neuropathy
      is seen as a spontaneous entrapment syndrome as well as a complication of
      orthopedic and vascular procedures performed on the medial area of the knee.
      Saphenous neuralgia is often not recognized by neurosurgeons. If the condition is
      intractable, it does respond to surgical therapy.

PMID- 1997902
TI  - Spinal man after declaration of brain death.
AB  - Complex spinal automatism in a patient who was declared brain dead is described.
      These movements tend to appear once cerebrospinal shock has abated. We postulate
      that these manifestations are a reflection of the physiological potential of the
      isolated spinal cord. These spinal movements should be included in the revised
      guidelines for the determination of cerebral death.

PMID- 1997903
TI  - Spinal cord compression from a thoracic paraganglioma: case report.
AB  - A 34-year-old man with a 4-month history of midthoracic back pain sought
      treatment for a recent onset of lower extremity paresthesia and stiffness. A
      myelogram and computed tomographic myelogram disclosed an extradural block at the
      level of the 8th thoracic vertebral body with involvement of the pedicles,
      lamina, and spinous process. A posterior decompression of the spinal cord with
      subtotal resection of a highly vascular tumor was performed. The tumor was
      identified as a paraganglioma. In a second stage, the remainder of the tumor was
      embolized preoperatively, and gross total excision and sequential stabilization
      of the spine with a Luque rectangle and sublaminar wires were performed. The
      patient has been symptom free and without signs of a recurrence in the spine for
      over 13 months. A large abdominal paraganglioma was recently resected from its
      probable origin from the adventitia of the abdominal aorta.

PMID- 1997904
TI  - Reversible hearing loss from cerebellopontine angle tumors.
AB  - We report two patients who presented with a dramatic recovery from severe
      sensorineural hearing loss after total surgical removal of cerebellopontine angle
      tumors (meningioma and jugular foramen neurinoma). The factors that differentiate
      these "non-acoustic tumors" in relation to the prognosis for hearing are
      discussed. A surgical approach that maintains the labyrinthine structure and
      preserves the arachnoid membrane of the superior cerebellopontine angle cistern
      during tumor removal is stressed.

PMID- 1997905
TI  - Adult peripheral neuroepithelioma in Meckel's cave.
AB  - A case of peripheral neuroepithelioma arising from the trigeminal nerve in
      Meckel's cave is presented. The discussion emphasizes the pathological criteria
      for the diagnosis of a peripheral neuroepithelioma and the current controversy
      about the classification of this and related tumors.

PMID- 1997906
TI  - Exposure of the intracavernous carotid artery in aneurysm surgery.
AB  - The pterional intradural approach was used in five cases of large and giant
      carotid-ophthalmic aneurysms and in two cases of intracavernous aneurysms that
      arose from the anterior siphon knee in the cavernous sinus (CS) and extended into
      the carotid cistern. In four cases of large carotid-ophthalmic aneurysms removal
      of the anterior clinoid process and the roof of the optic canal gave easy access
      to the pericarotid ring. The anteromedial part of the pericarotid ring was
      dissected to expose the extradural portion of the internal carotid artery (ICA)
      proximal to the neck and to make enough room between the wall of the CS and the
      extradural portion of the ICA, thus allowing easy clipping of the neck. In one
      case of a giant carotid-ophthalmic aneurysm extending into the CS with an
      extradural origin of the ophthalmic artery and in two cases of an intracavernous
      aneurysm arising from the siphon knee, neck clipping was performed by opening the
      lateral wall and roof of the CS after removal of the optic strut. The opening of
      the lateral wall anterior to the 3rd nerve facilitated wide exposure of the
      anterior siphon knee. The horizontal portion of the intracavernous ICA as well as
      the whole aspect of the aneurysm could be exposed as a result of the extended
      opening of the cavernous roof anterior to the posterior clinoid process.
      Successful operative results were obtained in all seven patients. A visual field
      detect as an operative complication was noted in one patient. No disturbance of
      ocular movements was noted.

PMID- 1997907
TI  - Monitoring of spinal cord stimulation evoked potentials during thoracoabdominal
      aneurysm surgery.
AB  - Repair of a thoracoabdominal aneurysm involves a significant risk of ischemic
      injury to the spinal cord. Standard monitoring of somatosensory evoked
      potentials, which relies upon peripheral nerve stimulation, becomes nonspecific
      and insensitive during this surgery when aortic cross-clamping produces lower
      extremity ischemia causing a peripheral conduction block. Techniques for the
      insertion of percutaneous epidural electrodes, developed originally for pain
      management, have been adapted to this setting to permit direct stimulation of the
      spinal cord for intraoperative monitoring of evoked potentials. The clinical
      outcome in patients monitored by this technique has been consistent with evoked
      potential findings.

PMID- 1997908
TI  - Hemorrhage into Rathke's cleft cyst.

PMID- 1997909
TI  - Lack of correlation between beta-endorphin and severity of cranial trauma.

PMID- 1997911
TI  - Basic care-givers American style. Statement on the proper use of assistive
      personnel to the registered nurse.

PMID- 1997910
TI  - In it together.

PMID- 1997912
TI  - Otitis media in pre-school children.

PMID- 1997913
TI  - A continuing smear campaign.

PMID- 1997914
TI  - Choosing the best care.

PMID- 1997915
TI  - National's approach to nursing.

PMID- 1997916
TI  - Employment Contracts Bill.

PMID- 1997917
TI  - The realities of managed care.

PMID- 1997918
TI  - What constitutes a medical malpractice claim.

PMID- 1997920
TI  - National Practitioner Data Bank: understanding its debits and credits.

PMID- 1997919
TI  - Polymer implantation in periodontic endodontic lesions. Two case reports.
AB  - A polymethylmethacrylate polymer was used in an attempt to fill periodontal
      osseous defects. Healing was within normal limits, probing depth and mobility
      were decreased, and there were no adverse post-operative sequelae. Although there
      were periapical radio-lucencies that appeared to be endodontic in origin,
      endodontic therapy did not result in osseous defect fill. The non-resorbable,
      radiopaque polymer particles appeared to become incorporated within the
      radiodense tissue of the osseous defects. The alveolar bone within the defects
      was seen to increase in radiopacity, consistent with osteogenesis.

PMID- 1997921
TI  - Occlusion as it relates to TMJ. A study of the literature.
AB  - References in this report are to papers that basically point toward similar
      findings. They have helped in the search for the etiology of TMJ dysfunction. We
      have tried to point out that there is no research that shows that restorative
      dentistry or orthodontics are etiological factors in TMJ dysfunction. The old bug
      a-boo about what causes TMJ--why it is more prevalent in women, etc.--is still
      under intensive study. Again, we should use a cautious approach to TMJ, be
      positive, be informed, and proceed with the right method, that is, a valid
      diagnosis before treatment.

PMID- 1997922
TI  - "The clam syndrome". Dental pain of unusual etiology.
AB  - Odontogenic pain may be due to periodontic or endodontic etiology. Myofacial and
      temporomandibular joint pain as well as sinusitis may cause referred pain to
      teeth. The following cases demonstrate yet another source of referred pain that
      could potentially cause a misdiagnosis.

PMID- 1997923
TI  - History's lesson.

PMID- 1997924
TI  - Striking a blow for advertising.

PMID- 1997925
TI  - Awards system questioned.

PMID- 1997926
TI  - Renal and ocular manifestations of hypertensive diseases of pregnancy.
AB  - Hypertensive diseases of pregnancy are commonly manifested in renal and ocular
      changes. Proper evaluation of findings provided by urine analysis, renal biopsy
      and examination of the optic fundi, visual acuity, and visual fields may help in
      assessing the severity of the disease and the need for obstetric intervention.
      Furthermore, renal and ocular changes are important guides in the differential
      diagnosis of hypertensive disorders of pregnancy. Renal and ocular lesions have
      also been found to have important prognostic implications. Review of the current
      knowledge on renal and ocular pathophysiologic changes induced by hypertension in
      pregnancy, may in addition shade light on the obscure etiology of this common
      entity.

PMID- 1997927
TI  - Uterine papillary serous carcinoma: a review.
AB  - Uterine papillary serous carcinoma, a histologic subtype of endometrial cancer,
      is characterized by a propensity for deep myometrial invasion, upper abdominal
      spread, and poor prognosis. We reviewed its histologic and clinical
      characteristics and compared them to those of endometrial adenocarcinoma with
      papillary features.

PMID- 1997928
TI  - The facts about practical nursing and medication administration.

PMID- 1997929
TI  - Political action: a responsibility for every registered nurse.

PMID- 1997930
TI  - Cimetidine and coumarin therapy of renal cell carcinoma. A pilot study.
AB  - Thirty-eight patients with metastatic renal-cell carcinoma (RCC) and 1 patient
      with a second primary RCC were treated with coumarin and cimetidine. Patients
      received 400 mg cimetidine p.o. daily and after 1 week 100 mg coumarin p.o. daily
      in addition until tumour progression. Two complete remission (30 and 50+ months)
      and 3 partial remissions (14, 13.8 months) could be achieved. Problems regarding
      possibly spontaneous regressions and comparable results of other treatment in RCC
      are discussed.

PMID- 1997931
TI  - Polymorphic oxidation of debrisoquine in women with breast cancer.
AB  - Oxidative polymorphism of debrisoquine (DBQ) was determined in 98 women with
      breast cancer (mean age 59.2 years, SD 10.7; 18 were premenopausal when
      diagnosed), and in 446 healthy control women (mean age 25.4 years, SD 9.15). All
      of them were free of drug interactions with oxidation of DBQ. Ten patients
      (10.2%), all of them postmenopausal when diagnosed, and 423 controls (5.2%), with
      values for metabolic ratio of DBQ greater than 12.6, were classified as poor
      metabolizers (PM) of DBQ (p = 0.006). Relative risk for developing breast cancer
      among women with PM phenotype was 2.09 (95% confidence limits 0.97-4.48). The PM
      status of DBQ might be a secondary risk factor for breast cancer in
      postmenopausal women.

PMID- 1997933
TI  - Antiemetic efficacy of droperidol or metoclopramide combined with dexamethasone
      and diphenhydramine. Randomized open parallel study.
AB  - We have performed an open parallel randomized study of the efficacy of two
      antiemetic drug combinations. Dexamethasone (10 mg i.v.), diphenhydramine (25 mg
      i.v.), and metoclopramide (3 mg/kg, 15 min i.v.) or droperidol (1.25 mg slow
      push) were given 30 min before and 90 min after start of chemotherapy. Thirty-six
      patients treated with cisplatin-based regimens (30 mg/m2 x 3 days or 60 mg/m2 day
      1 only), have been observed for 48 h after their last chemotherapy. Twelve (67%,
      confidence interval 95%: 41-87%) experienced no vomiting while on metoclopramide
      and 11 (61%, confidence interval 36-83%) were protected by droperidol. Further
      patient accrual was stopped because of side effects in one study arm. Moderate
      sedation (difficulty to keep up a conversation) was observed in 48% of those on
      metoclopramide versus 14% of those on droperidol (p less than 0.05). We conclude
      that low-dose droperidol combinations can offer antiemetic protection for
      patients treated with moderate-dose cisplatin-based chemotherapies. In view of
      the potential for severe long-term neurologic problems due to metoclopramide or
      droperidol, these and similar drugs should be used at the lowest possible dose.

PMID- 1997932
TI  - The antiemetic activity of high-dose metoclopramide and high-dose alizapride in
      combination with lorazepam in patients receiving cancer chemotherapy. A
      prospective, randomized, double-blind study.
AB  - The antiemetic efficacy of metoclopramide and lorazepam (MTC + L) versus
      alizapride and lorazepam (ALZ + L) was compared in 100 patients receiving
      chemotherapy, in a prospective randomized double-blind study. In highly
      emetogenic (HE) regimen (including platinum) patients received MTC 1 mg/kg or ALZ
      3 mg/kg x 4 doses, and lorazepam 2.5 mg 30 min before therapy. In moderately
      emetogenic (ME) regimen patients received MTC 0.5 mg/kg or ALZ 1.5 mg kg x 3
      doses, and lorazepam 2.5 mg 30 min before therapy. In both HE and ME regimen
      groups there was no statistically significant difference between MTC + L and ALZ
      + L treatments as regards the number of vomiting episodes, the duration of emesis
      and nausea, the intensity of nausea and side effects, but a statistically
      significant difference between treatments was found in the HE group where MTC-L
      was superior to ALZ + L in obtaining complete protection from vomiting (37 vs
      11%, p = 0.05). No significant difference in side effects was observed.

PMID- 1997934
TI  - Management of low-grade lymphomas in Hong Kong Chinese.
AB  - During a 14-year period, 122 of 840 (14.5) Hong Kong patients with non-Hodgkin's
      lymphomas were diagnosed to have low-grade lymphomas according to the Working
      Formulation. Only 28 (23%) of them had stage I and II disease and local
      radiotherapy appeared to be curative in some of them. Although remissions were
      achieved with chemotherapy in a majority of the stage III and IV patients, a
      pattern of continuous relapses was noted in their disease-free survival curve.
      Multivariate analysis revealed that clinical stage and presence of B symptoms
      were significant independent prognostic factors.

PMID- 1997935
TI  - Lower survival in metastatic cancer patients with reduced interleukin-2 blood
      concentrations. Preliminary report.
AB  - It is known that interleukin-2 (IL-2) plays a fundamental role in the generation
      of immune cells capable of mediating tumor regression. Since IL-2 may be often
      reduced in patients with disseminated cancer, a pilot study was started to
      evaluate which relation exists between IL-2 levels and survival in metastatic
      solid neoplasms. The study included 25 patients with metastatic disease (breast
      cancer: 12; non-small-cell lung cancer: 13). Serum IL-2 levels were measured by
      radioimmunoassay on venous blood samples collected before the start of
      chemotherapy. Breast cancer was treated with weekly epirubicin and lung cancer
      with cisplatin plus etoposide. Low levels of IL-2 were seen in 10/25 patients.
      Irrespectively of response to therapy and of dominant metastasis sites, the mean
      survival time was significantly lower in patients with reduced IL-2
      concentrations than in those with normal values. These results would suggest that
      the evidence of low IL-2 levels negatively influences the clinical course of
      patients with metastatic solid neoplasms.

PMID- 1997936
TI  - Leukocyte alkaline phosphatase and carcinoembryonic antigen in colorectal cancer
      patients (usefulness in the assessment of the stage).
AB  - Leukocyte alkaline phosphatase (LAP) scores in peripheral blood, and plasma
      carcinoembryonic antigen (CEA) levels were determined in 122 colorectal cancer
      patients, and compared to 30 healthy persons, who served as controls. Both
      markers are gradually elevated according to the severity of tumor penetration.
      LAP scores in Dukes'C and D (157 +/- 79) were significantly higher than in
      Dukes'A, B1 and B2 (81 +/- 43), p less than 0.001. CEA levels were also higher in
      Dukes'C and D (50 +/- 95) than in patients with Dukes'A, B1 and B2 (25 +/- 54), p
      less than 0.07, but less significantly. The LAP score has at least the same
      reliability as the CEA values as a marker of stage in colorectal cancer patients.

PMID- 1997937
TI  - Possible mechanism for the cocarcinogenic effect of bile acids: increased
      intracellular uptake of methylcholanthrene by C3H/10T1/2 fibroblasts in vitro.
AB  - The cocarcinogenic effect of bile acids on the chemical transformation of
      C3H/10T1/2 fibroblasts was examined in vitro. The assimilation of 3H
      methylcholanthrene (3H-MCA) by C3H/10T1/2 cells pretreated with bile acids was
      examined by the measurement of uptake and by autoradiography. Cells that were
      pretreated for 48 h with bile acids (100 microM lithocholic acid, 500 microM
      cholic acid) and then maintained in medium that contained 3H-MCA showed an
      increase in radioactivity compared to control cells. These results indicate that
      the transfer of carcinogens into cells is enhanced by pretreatment with bile
      acids.

PMID- 1997938
TI  - Expression of c-myc gene product in gastric carcinoma.
AB  - The expression of c-myc oncogene product was studied in 213 cases with gastric
      carcinoma by an immunoperoxidase method using a monoclonal antibody (MYC-1).
      Fifty (23.5%) of 213 tumors showed immunoreactivity to MYC-1. The distribution of
      c-myc-product-positive cells was observed mainly at the marginal area of the
      tumor. Excess reactivity to c-myc product occurred more frequently in invasive
      cancers than in localized cancers, and c-myc production expression in cancer
      tissue correlated well with peritoneal dissemination. Patients with c-myc-protein
      positive tumor had significantly poorer prognosis than those with c-myc-protein
      negative tumor in invasive gastric carcinomas, and the c-myc product status
      correlated well with the recurrence of cancer by peritoneal dissemination. These
      results suggest that the expression of c-myc gene product might be related to the
      proliferative activity of gastric carcinoma and serve as a new biologically
      relevant tumor marker for determining the prognosis.

PMID- 1997939
TI  - Sequential DNA flow cytometry in metastatic malignant melanoma.
AB  - Sequential flow cytometry was performed on 73 metastatic malignant melanomas,
      derived from 804 primary tumors. Tumor thickness was confirmed an excellent
      prognostic parameter in primary melanoma, but did not allow reliable predictions
      in metastatic disease. Also, aneuploidy and genetic heterogeneity, both common in
      metastatic melanoma, were equally distributed among patients differing in
      survival time. However, a remarkable acceleration was observed in the generation
      of abnormal cell lines in patients dying early of metastatic disease.

PMID- 1997940
TI  - Human colon cancer tissues are more sensitive than rectal cancer tissues to
      antitumor drugs in vitro.
AB  - The chemosensitivities of 62 human colon cancer tissues, 67 rectal cancer tissues
      and 31 tumor-adjacent normal mucosal tissues were determined using the in vitro
      succinate dehydrogenase inhibition (SDI) test. These tissues obtained at the time
      of surgery were exposed to carboquone (CQ), adriamycin (ADM), mitomycin C (MMC),
      aclacinomycin A (ACR), cisplatin (DDP) and 5-fluorouracil (5-FU). The
      chemosensitivity was considered as positive when succinate dehydrogenase (SD)
      activity of the drug-treated cells decreased to below 50% of that of control
      cells, on day 3 of exposure. Decrease in the SD activity was noted in the colon
      cancer tissues, compared to the rectal cancer tissues, exposed to six antitumor
      drugs and in particular, to CQ (p less than 0.05), DDP (p less than 0.01) and ACR
      (p less than 0.05, one-sided paired t test). Decrease in the SD activity was
      noted in the tumor tissues, compared to the tumor-adjacent normal tissues,
      exposed to CQ, MMC and ACR (p less than 0.01). The sensitive rates were higher in
      the colon cancer tissues than the rectal cancer tissues, against all six
      antitumor drugs. Our findings show that the rectal cancer tissues are resistant
      to antitumor drugs, compared to the colon cancer tissues in vitro. When selecting
      antitumor drugs to treat patients with a rectal cancer, the assessment for
      chemosensitivity of the related tissues is crucial.

PMID- 1997941
TI  - Immunocytochemical staining of proliferating cells in endoscopically biopsied
      tissues of gastric carcinomas with monoclonal antibody Ki-67.
AB  - The growth fractions in endoscopically biopsied materials from 121 patients with
      gastric carcinomas were determined by immunohistochemical staining with the
      monoclonal antibody Ki-67 and the results correlated with the histopathologic
      findings and clinical outcome. The Ki-67 labeling rates ranged from 4.6 to 52%
      (mean: 22%). A significant correlation was found between Ki-67 labeling rates of
      biopsied materials and those of resected specimens. The tumors showing Ki-67
      labeling rates of greater than 22% are more likely to have lymph node metastasis,
      lymphatic invasion of serosal invasion than those with the rates below 22%. In
      addition, Ki-67 labeling rates were closely associated with prognosis. Tumors
      with high Ki-67 labeling rates (greater than 22%) were related to poor prognosis,
      whereas those with low Ki-67 labeling rates were associated with favorable
      prognosis. The immunohistochemical staining of proliferating cells in
      endoscopically biopsied specimens of gastric carcinomas using the Ki-67
      monoclonal antibody may be useful in assessing prognosis in carcinoma of the
      stomach.

PMID- 1997942
TI  - Nucleolar organizer regions in soft tissue sarcomas.
AB  - Argyrophilic proteins of nucleolar organizer regions (AgNORs) were studied in a
      series of 65 sarcomas of the soft tissues and 2 cases of fibrohistiocytic tumors
      of intermediate malignancy. The numbers of AgNORs per nucleus and the size of
      AgNORs were determined and compared with pathomorphologic parameters such as
      grading of malignancy, cellularity and tumor diameter. The main finding of this
      study was that AgNOR counts showed significant differences between low-grade
      malignant (G 1) and high-grade malignant (G 3) tumors predominantly based on a
      correlation with the frequency of mitosis. All the other criteria of tumor
      grading (nuclear pleomorphism, differentiation, amount of necrosis), tumor
      diameter and cellularity showed no differences with regard to AgNOR counts.
      Though it was observed that tumor giant cells possessed predominantly coarse
      granular AgNORs, no correlation was found between AgNOR size and any of the
      parameters investigated. In spite of a clear statistically significant result
      gained by an evaluation of all cases, a heterogeneity of AgNORs in relation to
      mitotic activity within a few histological tumor types could be observed, making
      it difficult to suggest the determination of AgNORs as a parameter with general
      validity for all soft tissue sarcomas.

PMID- 1997943
TI  - Adriamycin-induced neoplastic lesions in the Egyptian toad Bufo regularis.
AB  - Injecting adult toads (Bufo regularis) subcutaneously in the dorsal lymph sac
      with adriamycin at a dose of 2 mg/kg body weight, once every 3 weeks for 20
      weeks, induced hepatocellular carcinomas in 20 out of 100 animals. Metastases of
      the primary liver tumors appeared in the kidneys of 7 toads.

PMID- 1997944
TI  - Combination of idarubicin and cyclophosphamide administered orally in untreated
      postmenopausal breast cancer patients. A phase II study.
AB  - On the basis of results obtained with oral idarubicin administration in breast
      cancer, which have shown an established antitumor activity in approximately 28%
      of cases, this compound was combined with cyclophosphamide (also given orally) in
      postmenopausal patients with an unknown or negative steroid receptor status. The
      study comprised 45 untreated patients out of which 44 were evaluable for response
      and toxicity. The mean age was 62.5 years (range 51-75). The majority of patients
      had soft tissue (24) and visceral organ (17) metastases. Idarubicin was
      administered in one oral daily dose of 45 mg/m2 on day 1; the oral
      cyclophosphamide dose was 200 mg/m2 daily on days 3, 4, 5 and 6. An objective
      response to treatment was observed in 41% of patients (18/44, 95% confidence
      interval 28-56%). Complete remission (lung) was observed in 2 patients (5%),
      while 16 patients achieved a partial response. Eleven patients showed no change,
      while 15 patients progressed. A particularly good response was obtained in soft
      tissue metastases (54%, 13/24) while in visceral organs a response was achieved
      in 31% of patients (5/16). The remissions lasted 2-14 months (median 7 months),
      and median survival was 14+ months. Toxicity was mild and the treatment well
      tolerated. Grade I/II leukopenia was observed in 24% of patients (median WBC
      nadir 3,100); there were no signs of cardiotoxicity. Grade I and II alopecia was
      observed in 75% of patients: nausea/vomiting were present in 73% of cases. The
      results of this study indicate that oral administration of idarubicin and
      cyclophosphamide produces a valuable antitumorigenic effect in postmenopausal
      breast cancer patients, particularly in soft tissue metastases. Further
      randomized studies will be needed to evaluate this treatment approach.

PMID- 1997945
TI  - Walking along human c-myc mRNA with antisense oligodeoxynucleotides: maximum
      efficacy at the 5' cap region.
AB  - A series of antisense pentadecamers complementary to a variety of target
      sequences between the cap and AUG initiation codon regions of c-myc mRNA was
      synthesized and used to treat human promyelocytic leukemia HL-60 cells. The
      sensitivity of the cap-region sequences to antisense inhibition of c-myc p65
      expression was two to three times that of the original initiation codon antisense
      sequence. The other target sequences downstream of the cap and up to the AUG
      initiation codon were comparable to the initiation codon sequence, except that
      the first splice junction was slightly more sensitive. At the primary initiation
      codon target, a dodecamer was about half as effective as the original
      pentadecamer, whereas an octadecamer was about twice as effective. The
      observation of variation in antisense efficacy as a function of target location
      in c-myc mRNA may represent a combination of the effects of hybrid arrest, RNase
      H attack, and interference in RNA processing. Alternatively, the most sensitive
      targets might be those that are the most exposed in the secondary and tertiary
      structure of c-myc mRNA.

PMID- 1997946
TI  - Daily addition of an anti-c-myc DNA oligomer induces granulocytic differentiation
      of human promyelocytic leukemia HL-60 cells in both serum-containing and serum
      free media.
AB  - Expression of the human protooncogene c-myc is necessary for replication, and may
      be inhibited in a sequence-specific, dose-dependent manner by an antisense
      oligodeoxynucleotide specific for the first five codons of c-myc mRNA. Antisense
      inhibition of c-myc inhibits the proliferation and enhances the differentiation
      of the HL-60 human promyelocytic leukemia cell line. In order to raise the
      efficacy of antisense oligomers, HL-60 cells were grown in a serum-free medium so
      as to minimize nuclease activity in the culture medium. Daily addition of anti-c
      myc oligomer was then found to induce terminal granulocytic differentiation of
      80% or more of HL-60 cells, and inhibit colony formation by greater than 50%,
      comparable to 1% Me2SO.

PMID- 1997948
TI  - Division plays pivotal role in state society's priorities.
AB  - Last session's legislative scales most often tipped in favor of Pennsylvania
      physicians on issues we addressed. State Society-endorsed laws are in place
      concerning AIDS confidentiality, medical education funding levels, and a
      statewide task force on drug and alcohol abuse. A score of Society-opposed
      measures have been defeated. Meanwhile, battle continues on portions of the
      Medicare balance billing law and the auto insurance law.

PMID- 1997947
TI  - Binding of a nuclear factor to the upstream region of the c-myc gene.
AB  - We have studied the binding of proteins to a synthetic DNA fragment corresponding
      to a 21 base pair sequence in the upstream region of the human c-myc gene. This
      sequence has previously been reported to bind the c-myc protein, thus
      representing a putative site for autoregulation of the c-myc gene (Ariga et al.,
      1989). Our electrophoretic mobility shift assays indicated that this DNA fragment
      binds to a factor present in nuclear extracts from HeLa cells. However, analysis
      of extracts from other cells indicated that this binding does not correlate with
      the presence of the c-myc protein. No binding was observed using c-myc protein
      translated in vitro. Also, anti-c-myc antibodies could not inhibit binding of
      this factor. These experiments indicate, that nucleotides -2193 to -2173 from the
      P1 promoter of the c-myc gene are able to bind a nuclear factor, and that this
      factor most likely does not include the c-myc protein.

PMID- 1997949
TI  - Are eggs hazardous to your health?

PMID- 1997950
TI  - Forensic pathology's dilemma: state death certificate.
AB  - Forensic pathologists are familiar with the intricacies and importance of death
      certificates. But Pennsylvania physicians also need an updated, working knowledge
      of these vital documents. Members of the PMS Resident Physician Section have
      urged the State Society to support guidelines to help "clean up" the errors.

PMID- 1997951
TI  - State code remains silent on living will law despite Cruzan case.

PMID- 1997952
TI  - Federal budget policies have dire consequences.

PMID- 1997953
TI  - Articular fractures of the hand. Part I: Guidelines for assessment.
AB  - Articular fractures of the hand represent a particularly challenging group of
      injuries owing to the frequent comminution of the fractured bone, disruption of a
      finely balanced soft-tissue sleeve, and a propensity for scarring and
      contractures. Assessment of these fractures must include accurate delineation of
      the injury, using roentgenographic and computed tomographic imaging to define
      articular congruency, and a precise examination to determine stability.

PMID- 1997954
TI  - Vertebral aneurysmal bone cyst. A case report and review.
AB  - The case of a 16-year-old boy with an aneurysmal bone cyst of the fourth lumbar
      vertebra and a herniated nucleus pulposus of the L4-5 disc is presented. Symptoms
      included progressive lower back pain and bilateral lower extremity weakness.
      Roentgenographic studies were consistent with a vertebral aneurysmal bone cyst
      with an expansile lesion that compromised the neural canal and an L4-5 herniated
      nucleus pulposus. Surgical treatment included tumor excision, L4-5 discectomy,
      lumbar decompression, and posterolateral and anterior lumbar fusion.
      Postoperatively, the lower back pain and lower extremity symptoms resolved. The
      patient continues to do well at 1-year follow-up.

PMID- 1997955
TI  - Use of survivorship and contact stress analyses to predict the long-term efficacy
      of new generation joint replacement designs. A model for FDA device evaluation.
AB  - Long-term investigational device exemption (IDE) clinical trial evaluation, as
      currently monitored by the Food and Drug Administration (FDA) regulatory process,
      is time-consuming, burdensome, and extremely costly to the product developers and
      ultimately to the consumer. Thus, almost all devices introduced in the past
      decade have not been clinically tested; they have been introduced under a "510k"
      grandfather provision that does not address the safety and efficacy of the
      product. As a result, joint replacement devices have been sold and used with
      serious failure consequences for the consumer. When 10-year survivorship studies
      are available for specific joints that demonstrate strong evidence of favorable
      clinical performance with suitable supporting analysis, they can be used as a
      standard for comparison with newer, similar designs. Additionally, contact stress
      analysis of the bearing surfaces of these joint replacements can be used to
      determine their long-term wear characteristics under normal loading conditions
      and compared to retrieved devices used for 10 years or more. Devices that
      demonstrate a 90% survivorship over a 10-year interval and have low enough
      contact stresses to minimize wear failure during the same period can be used as
      "standard designs" to which newer designs should be compared. Using this
      methodology, the developers of any new device should cite the standard design
      that they have improved on and document an improvement in early (1 to 3 years)
      survivorship studies with a contact stress analysis demonstrating bearing contact
      stresses equal to or lower than the standard design. Any device that fails more
      often or wears out faster than a standard design should not be released until
      design modifications have proved it superior or equal to the standard designs.

PMID- 1997956
TI  - Luque interpeduncular segmental fixation of the lumbosacral spine.
AB  - Interpeduncular segmental fixation of the lumbar and lumbosacral spine with Luque
      screws and plates is becoming increasingly popular. In this retrospective study,
      52 consecutive patients treated with this technique were followed for 16 to 44
      months (average, 21). Indications for surgical arthrodesis included lumbar
      instability from degenerative disease (16 cases), spondylolisthesis (25 cases),
      pseudarthrosis (eight cases), fracture (two cases), and tumor (one case). Fusion
      with instrumentation spanned one level in nine patients, two in 38 patients,
      three in four patients, and four in one patient. Patients wore a rigid lumbar
      orthosis for an average of six months (range, two to 16). Ten complications
      occurred in nine patients: two superficial wound infections, four neurologic
      complications, three loosened screws, and one broken screw. An overall fusion
      rate of 96% was achieved; pseudarthrosis is suspected in one case and failed
      arthrodesis secondary to trauma in a second patient. At four months
      postoperatively, solid unions had resulted in most of the cases, as seen
      roentgenographically. All patients reported decreased back pain; however, one
      patient is addicted to narcotics. Twenty-five of the 29 patients employed were
      able to return to work at an average of six months postoperatively.

PMID- 1997957
TI  - Arthroscopy update #9. Posterior compartment observation and instrumentation in
      the knee using anteromedial and anterolateral portals and an interchangeable
      cannula system.
AB  - The technique for routine posterior compartment observation in the knee described
      here uses cannulae that are 75 mm long and either 4.6 mm or 5.6 mm in diameter.
      Once they have been introduced, they remain in place while instruments and the
      arthroscope are interchanged within them. The arthroscope is attached to a bridge
      that connects to either cannula. Anteromedial and anterolateral portals are used
      with the interchangeable cannulae system. Once the arthroscope has been attached
      to the cannula in the anterolateral portal, an identical cannula with a blunt
      obturator is passed from the anteromedial portal into the posterolateral
      compartment under direct vision. The position of the arthroscope and blunt
      obturator are then reversed so that the arthroscope views the posterolateral
      compartment. To view the posteromedial compartment, the maneuver is repeated with
      the arthroscope in the anteromedial portal. The cannula with the blunt obturator
      is then advanced from the anterolateral portal under direct vision into the
      posteromedial compartment, and the position of the arthroscope and obturator are
      again interchanged. Hypertrophic synovium and osteophytes in the notch can be
      removed by passing shavers or burrs through the cannulae. Posteromedial and
      posterolateral portals are established with the 70 degree arthroscope under
      direct vision; once a cannula has been placed in a posterior portal,
      instrumentation and observation through the posterior cannula can be performed.
      The cannula from the opposite anterior portal remains in the posterior
      compartment. Hand and power instruments can be passed safely across the notch and
      into the posterior compartments while viewing the procedure through the
      posteriorly positioned arthroscope. The posterior cruciate ligament is then
      observed from the posteromedial portal while palpating the ligament with
      instruments entering the posterior compartment from the anterolateral portal.

PMID- 1997959
TI  - Abstracts of papers. Pharmaceutical and biomedical analysis meeting. Eindhoven
      (The Netherlands), 16 November 1990.

PMID- 1997958
TI  - Tips of the trade #32. Gradual closure of fasciotomy wounds.
AB  - A technique of gradual closure of fasciotomy wounds is presented. At the time of
      fasciotomy, staples are placed at the edge of the fasciotomy wound. A large nylon
      suture is threaded through the staples in a pattern similar to the lacing of a
      shoe. Postoperatively, this suture is tightened daily; this results in gradual
      closure of the wounds without further surgery.

PMID- 1997960
TI  - Abstracts of papers. Pharmacochemistry in The Netherlands: then, now and in the
      future. Weesp (The Netherlands), 14 December 1990.

PMID- 1997961
TI  - Changes in the Nurse Practice Act.

PMID- 1997962
TI  - Past imperfect; future perfect?

PMID- 1997963
TI  - National health care: necessary but not sufficient.

PMID- 1997964
TI  - At the expense of their souls.
AB  - Thirty experienced public health nurses in western Washington were interviewed to
      determine how they knew that they had improved their clients' lives. Although
      they still perceive themselves as making a difference, their remarks reveal that
      clients' substance abuse and violence are threatening the nurses' own physical
      and emotional well-being.

PMID- 1997966
TI  - The nursing shortage in the context of national health care.
AB  - The notion of a "nursing shortage" implies that all nurses are interchangeable
      and is another indication that nurses are labelled "professional" without
      enjoying the benefits of that status. Nurses can reassert their professional
      status by becoming the architects of a radically new health care structure that
      guarantees health care for all.

PMID- 1997965
TI  - Latvian nurses depart from Soviet ways.
AB  - As their country tries to break away from the Soviet political system, Latvian
      nurses try to break away from a Soviet health care system that has relegated
      their profession to one completely dominated by physicians. Two Latvian-born
      American nurses provide a glimpse of the early stages of this struggle.

PMID- 1997967
TI  - Toward a national policy for nursing.
AB  - New Jersey's Nursing Incentive Reimbursement Award program provides competitive
      grants to hospitals to develop innovative nursing service programs that improve
      patient care. The program's overarching concept is that nursing ideas and action
      should percolate up to the State Health Department level from the level of direct
      care providers.

PMID- 1997968
TI  - When discrimination supersedes confidentiality.
AB  - Recent decisions have made it clear that the courts are now less inclined to
      apply the doctrine of academic abstention in cases regarding discrimination in
      promotion and tenure. Colleges and universities with closed rank and tenure
      proceedings can now expect to be challenged by unsuccessful candidates suspecting
      discrimination.

PMID- 1997969
TI  - Changes in nursing's periodical literature: 1975-1985.
AB  - A comparison of 1975 and 1985 nursing journals reveals that more and better
      educated nurses are writing the profession's articles than was the case 15 years
      ago. Findings point to a significant growth in the professionalism of the nursing
      literature.

PMID- 1997970
TI  - Bring back big nurse.

PMID- 1997971
TI  - Nancy Cruzan is allowed to die, but uncertainties remain.

PMID- 1997972
TI  - 5-Fluorouracil and recombinant interferon alfa-2a: review of activity and
      toxicity in advanced colorectal carcinomas.
AB  - Improved response rates in metastatic colorectal carcinoma recently have been
      observed for the combination of 5-fluorouracil (5-FU) and recombinant interferon
      alfa-2a (rIFN), compared to those obtained in historical trials of single-agent 5
      FU. The mechanism of interaction between these agents has not been explored
      adequately but may relate to biochemical modulation of 5-FU by rIFN. Toxicities
      resulting from this combination have included fever, chills, myalgias,
      granulocytopenia, mucositis, diarrhea, skin rash, neurological symptoms, and hand
      foot syndrome. Future studies of 5-FU with rIFN should investigate schedules
      aimed at reducing toxicity without compromising efficacy and also should explore
      mechanisms of enhanced activity.

PMID- 1997973
TI  - Coping with biotherapy: physiological and psychosocial concerns.
AB  - Cancer treatment with biological response modifier (BRM) therapies is
      characterized by many of the same issues observed with other modalities. Yet, the
      nurse caring for the patient receiving BRM therapy frequently is faced with the
      need to develop interventions that respect both the integrity of investigational
      studies and the patient's unique needs. Coping with BRM therapy is influenced by
      many factors. Several models may be used simultaneously to assess coping
      behaviors and to provide effective interventions. The goals of investigational
      therapy and the management of symptom distress influence the ability to cope with
      BRM therapy. The interruption or impediment of normal adult developmental
      activities also influences the individual's response to the psychological
      stressors associated with this cancer therapy. Consequently, the most significant
      challenge faced by anyone receiving cancer therapy is the same for the individual
      receiving BRM therapy--living with uncertainty.

PMID- 1997974
TI  - Physical symptoms of combination biotherapy: a quality-of-life issue.
AB  - Data are available on the principal side effects of individually administered
      biological response modifiers (BRMs). However, studies on physical symptoms
      secondary to multiagent regimens (i.e., combinations of BRMs and of BRMs and
      chemotherapy) are just now appearing in the literature. The combinations of alpha
      interferon and 5-FU and of alpha interferon and interleukin-2 (IL-2) are the
      focus of this paper. Published and unpublished reports of side effects associated
      with these combinations are reviewed, and resulting quality-of-life (QOL) issues
      examined. Physical side effects that may affect QOL are flu-like symptoms,
      gastrointestinal (GI) toxicities, and fatigue, which may alter social,
      physiological, and psychological function and negatively influence the perception
      of QOL. Nursing interventions to improve these reactions include awareness and
      assessment of the patient's perception of QOL and strategies to alleviate the
      symptoms. Numerous opportunities exist for nursing research on improved symptom
      management and on QOL in combination biotherapy regimens.

PMID- 1997975
TI  - Alpha interferon: perspectives in the biotherapy of chronic myelogenous leukemia.
AB  - Chronic myelogenous leukemia (CML) is a clonal disorder characterized by a
      cytogenetic translocation, the Philadelphia chromosome (Ph). CML terminates in
      blastic transformation with additional secondary cytogenetic events. Standard
      chemotherapy rarely results in Ph suppression and is associated with three- to
      four-year overall survival. Alpha interferon has a mechanism of action distinct
      from that of chemotherapy. Although the percentage of patients that can be
      expected to achieve complete hematologic remission (CHR) with alpha interferon is
      similar to the percentage expected with chemotherapy, nearly 40% of patients
      undergoing treatment with alpha interferon have some degree of Ph suppression.
      Present studies will determine whether interferon delays blastic transformation
      and improves survival in CML. This paper addresses current issues in the alpha
      interferon therapy of this malignancy, such as optimum dose, duration of therapy,
      antibody formation, toxicities, and altered characteristics of blastic
      transformation. Alpha interferon will have a major role, both therapeutic and
      prognostic, in the management of CML.

PMID- 1997976
TI  - Noninvasive assessment of coarctation of the aorta: comparative measurements by
      two-dimensional echocardiography, magnetic resonance, and angiography.
AB  - Fifteen patients, aged between 9 and 21 years (mean, 15.1), with native
      coarctation of the aorta (CoA) or suspected recoarctation after surgical repair,
      underwent three different diagnostic procedures. Two-dimensional echocardiography
      (2D echo) and magnetic resonance imaging (MRI) of the thoracic aorta were
      performed in all patients; 14 patients underwent aortography, and digital
      subtraction angiography of the aorta was performed in one (after injection via a
      central venous catheter). Conventional electrocardiographic (ECG) gated MRI was
      performed, using the sagittal plane, a 256 x 256 acquisition matrix, multi-slice
      technique and a slice thickness of 10 mm. Diameters at the coarctation site were
      determined by all methods. Additional diameters of the descending aorta and the
      aortic arch were measured by MRI and echocardiography, respectively. All
      noninvasively obtained diameters were compared with angiographic data. Ultrasound
      imaging of the aortic isthmus was achieved in seven of 15 patients and of the
      aortic arch in nine of 15. The mean difference compared with angiographically
      determined diameters was 1.7 (0-7) mm, being greater for the coarctation site
      [mean, 2.2 (0-4)]. MRI images of the aortic isthmus were obtained in all
      patients, but the difference to angiographically determined diameters was
      slightly higher [mean, 3.2 mm (0-8)] than the ultrasound results. This deviation
      was presumably due to technical conditions, such as slice thickness and
      orthogonal imaging planes. Including all diameters, the correlation to invasive
      measurements was r = 0.82 (SEM = 3.1) for MRI and r = 0.89 (SEM = 2.3) for echo
      recordings.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1997977
TI  - Cardiac output by pulsed Doppler in neonates using the apical window.
AB  - In 18 healthy neonates, cardiac output was measured by range-gated Doppler
      echocardiography with simultaneous two-dimensional echocardiography, using the
      apical approach. Maximal and modal flow velocities were compared by using
      spectral analysis of the Doppler signal. Blood flow velocities were measured in
      the left ventricular outflow tract and in the ascending aorta. Cardiac index
      (cardiac output per kg body weight), with the sample volume placed in the left
      ventricular outflow, averaged 170 +/- 45 ml/min/kg in the maximal flow velocity
      mode and 133 +/- 39 ml/min/kg in the modal mode, respectively (p less than 0.05).
      Sampling in the ascending aorta gave cardiac index values of 198 +/- 73 ml/min/kg
      in the maximal velocity and 167 +/- 58 ml/min/kg in the modal velocity mode.
      Maximal flow velocities in the ascending aorta came closest to published data
      obtained by invasive and noninvasive methods.

PMID- 1997978
TI  - Pulmonary artery pressure evaluated by pulsed Doppler echocardiography in
      children with a left-to-right intracardiac shunt.
AB  - In a study of 25 children with left-to-right intracardiac shunt we found a good
      correlation (r greater than 0.92; p less than 0.001) between right ventricular
      pre-ejection period/acceleration time, derived from pulsed Doppler
      echocardiography, and pulmonary artery systolic, diastolic, and mean pressures,
      measured at cardiac catheterization. This may enhance the noninvasive estimation
      of pulmonary artery pressure.

PMID- 1997979
TI  - Exercise testing in children with congenital heart disease before and after
      surgical treatment.
AB  - Pre- and postoperative exercise tests were performed on 12 children with severe
      congenital heart disease (CHD) (age, 4-12 years). Oxygen uptake, blood pressure,
      and heart rate responses to exercise were measured. Exercise test time and the
      tolerable speed of the treadmill increased significantly after the operation.
      When pre- and postoperative values were compared, exercise heart rates did not
      change in most of the children, while delta systolic blood pressure rose
      significantly. The significant increase in peak oxygen consumption (VO2/Kg)
      values also revealed that there was an improvement in their exercise capacity
      after the operation.

PMID- 1997981
TI  - Percutaneous transluminal coronary angioplasty for Kawasaki disease: a case
      report and literature review.
AB  - A 31-month-old boy developed right coronary artery stenosis after Kawasaki
      disease for which he underwent percutaneous transluminal coronary angioplasty
      (PTCA). The narrowing of the right coronary artery was successfully dilated by
      angioplasty without apparent complication. This case suggests that PTCA may have
      a potential advantage as a temporary method to postpone the aortocoronary bypass
      surgery in a child with coronary artery stenosis due to Kawasaki disease.
      However, strict patient selection is recommended for coronary angioplasty.

PMID- 1997980
TI  - Cardiac function in congenital hypothyroidism: impairment and response to L-T4
      therapy.
AB  - Electrocardiograms (heart rate, QRS voltage, QRS axis in the frontal plane. Q-Tc
      interval) echocardiograms [left ventricular fractional shortening (LVFS);
      preejection period (PEP); PEP/left ventricular ejection time (PEP/LVET) ratio;
      end-diastolic left ventricular free wall and interventricular septum thickness;
      presence of pericardial effusion], and thyrotropin (TSH), thyroxine (T4), and
      triiodothyronine (T3) serum levels were evaluated before and 1 week, 1 and 2
      months after the start of L-thyroxine (L-T4) therapy in 11 infants with
      congenital hypothyroidism (CH), aged 16-59 days when first seen. Before the start
      of therapy, infants with CH had significantly lower QRS complexes and LVFS and
      significantly higher values for Q-Tc, PEP, and PEP/LVET than normal infants of
      the same age. The QTc interval, PEP and PEP/LVET ratio of infants with CH were
      significantly greater before than 1 week after L-T4 therapy, and LVFS was
      significantly lower before than 1 month after L-T4 therapy. Four of the infants
      with CH had small pericardial effusions, which disappeared within the first week
      of therapy. QRS axis in the frontal plane, Q-Tc interval, and PEP were negatively
      correlated with logT4 and logT3 serum levels. PEP/LVET ratios were negatively
      correlated with logT4 serum values. The QRS voltage values were positively
      correlated with logT4 and logT3 serum values. The frontal-plane QRS axis, Q-Tc
      interval, and PEP/LVET ratio were positively correlated with logTSH serum levels.
      The QRS voltages were negatively correlated with TSH serum levels.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1997982
TI  - Ventricular fibrillation during transesophageal atrial pacing in an infant with
      Wolff-Parkinson-White syndrome.
AB  - A complication of transesophageal atrial pacing in an infant with Wolff-Parkinson
      White syndrome (WPW) is reported. A newborn infant born with fetal hydrops had
      recurrent supraventricular tachycardia (SVT) that required repeated successful
      conversion by transesophageal atrial pacing. Because of secondary left
      ventricular dysfunction, digoxin was administered. During repeat transesophageal
      atrial pacing for recurrent SVT, ventricular fibrillation occurred. Although it
      is unclear which of several possible contributing factors was responsible for the
      ventricular fibrillation, recommendations are appropriate to minimize the risk in
      infants with WPW.

PMID- 1997983
TI  - The subclavian artery as the first branch of the aortic arch.

PMID- 1997984
TI  - Aberrant left pulmonary artery with tracheal stenosis without vascular sling.
AB  - We report a case of abnormal origin of the left pulmonary artery from the right
      pulmonary artery, associated with tracheal stenosis but with no vascular sling.
      This is the first such case, to our knowledge, without vascular sling.

PMID- 1997985
TI  - Aortic atresia with aortopulmonary window and interruption of the aortic arch.
AB  - The cross-sectional echocardiographic and postmortem appearances of the heart
      from a patient with the rare association of aortic valve atresia, aortopulmonary
      window, and interrupted aortic arch are described. Differentiation of this
      anomaly from truncus arteriosus with interrupted aortic arch is important.

PMID- 1997986
TI  - Intrapericardial teratoma causing nonimmune hydrops fetalis and pericardial
      tamponade: a case report.
AB  - A case of fetal anasarca secondary to an intrapericardial teratoma is reported.
      The clinical, echocardiographic, and histologic features are described, along
      with a review of intrapericardial lesions.

PMID- 1997987
TI  - Unusual evolution of a pericardial mass diagnosed by fetal echocardiography.
AB  - An intrapericardial mass with a pericardial effusion was diagnosed by ultrasound
      examination in the fetus of a 29-year-old gravida 1 para 0 woman at 32 weeks'
      gestation. Serial in utero examinations showed disappearance of the pericardial
      effusion at 35.5 weeks' gestation, while the mass remained unchanged. Vaginal
      delivery ensued at 39 weeks. Clinical and echocardiographic examination of the
      newborn revealed normal cardiac anatomy with no abnormal mass or pericardial
      effusion. Follow-up examinations confirmed these normal data.

PMID- 1997988
TI  - Two-dimensional and Doppler echocardiographic assessment of variably shaped
      ductus arteriosus by the parasternal approach.
AB  - Parasternal two-dimensional and Doppler echocardiography were compared with
      angiographic, surgical, and postmortem data in 213 patients with various forms of
      congenital heart disease for its accuracy in determining patency and anatomy of
      the ductus arteriosus (DA). The age range of the examined patients was from 1 day
      to 4 years (mean, 7.4 months). Echocardiography was always performed before any
      invasive procedure. An adequate window for imaging the DA was obtained by
      parasternal, two-dimensional echocardiography in 209 patients (98%). A persistent
      ductus arteriosus (PDA) was detected by invasive methods in 79 of 209 patients
      (38%), and by two-dimensional and Doppler echocardiography in 76 (sensitivity,
      96%; specificity, 100%). The echocardiographic and angiographic findings agreed
      closely as to the duct's morphology. Our technique permits an accurate
      visualization of the duct in neonates, infants, and small children with various
      forms of congenital heart disease.

PMID- 1997989
TI  - Echocardiographically directed angiography in congenital heart disease.

PMID- 1997990
TI  - Cyanotic atrial septal defect in a premature infant.

PMID- 1997991
TI  - Absent pulmonary valve syndrome with tetralogy of Fallot: a rare radiographic
      presentation.

PMID- 1997992
TI  - Pulmonary vascular sling.

PMID- 1997993
TI  - Surgical closure of aortopulmonary window without cardiopulmonary bypass.

PMID- 1997994
TI  - Integrated versus separate patient education.

PMID- 1997995
TI  - Pediatric asthma, a qualitative and quantitative approach to needs assessment.
AB  - This article describes an approach to needs assessment in a specific location
      using both focus group interviews and a written questionnaire. In this case
      study, the target population consists of parents of asthmatic children (0-4 years
      of age). Six focus group interviews were conducted with the purpose of discussing
      parents' experiences with health care for asthma, their beliefs and knowledge of
      general aspects of asthma, medication and preventive actions. As a supplement,
      parents completed a written questionnaire providing additional quantitative
      information on parental knowledge and misconceptions. Results indicated that
      parental knowledge of asthma in general was not adequate, especially with respect
      to medication, preceding signs and preventive activities. Important
      misconceptions, which might contribute to noncompliance with self-management
      behaviors, were revealed during discussions with the parents. Several differences
      were found between results of the interviews and the questionnaire, for instance
      regarding parental knowledge about preventive measures, medication and perceived
      parental satisfaction with health care for asthma. These differences indicate the
      value of using both a survey and a focus group.

PMID- 1997996
TI  - Pediatric patient education: the unanswered challenge to medical education.
AB  - As many as 10-20% of pediatric patients in this country have a chronic illness.
      This number will likely increase. Unfortunately, there has not been a parallel
      growth in physicians acquiring knowledge and skills in patient education. The
      disparity between these high tech and high touch skills is the most logical
      explanation why the morbidity in some chronic illnesses like asthma has not
      improved despite recent advances in diagnosis and treatment. The discussion
      focuses on the barriers to patient education and why it has not been a more
      integral part of caring for chronically ill children and their families. The
      solutions to this problem are complex but must include the willingness of health
      care professionals to welcome patients and their families as partners in the
      process. In addition, there is a need for change in the medical education system
      so that patient education is taught as a continuum, beginning with principles and
      theory and concluding with application to patient care.

PMID- 1997997
TI  - You Can Control Asthma: evaluation of an asthma education program for
      hospitalized inner-city children.
AB  - A self-management education program was designed for staff nurses to offer
      children while they received medical care for asthma in the hospital. The program
      uses videotapes, written activity books and nurse discussion with the patient.
      Evaluation was conducted to assess program feasibility and impact. Pre- and post
      tests of 40 children age 6-12 years revealed that the children had statistically
      significant increases in knowledge of and expected response to early warning
      signs of acute asthma, and in their sense of personal control (Health Locus of
      Control). Parents reported an increased use of asthma self-management techniques
      for acute episodes of asthma. Medical record review for a 15 month pre- and post
      period indicated reductions in emergency room use. Inpatient hospital based
      education offers a critical opportunity to introduce asthma management skills,
      especially to children not reached by more traditional programs.

PMID- 1997998
TI  - A relationship between perceived self-efficacy and quality of life in cancer
      patients.
AB  - The quality of life of cancer patients may be influenced by the degree of control
      they feel able to exert over stressful situations arising from having the
      disease. We were able to test this association using a newly developed
      instrument, the Stanford Inventory of Cancer Patient Adjustment which assesses
      perceived self-efficacy, that is, perceived ability to enact coping strategies.
      In a heterogeneous sample of 273 cancer patients a strong positive correlation
      was found between self-efficacy and quality of life and between self-efficacy and
      mood. Improvements in all three measures brought about by a brief, group program
      teaching coping skills were also highly correlated. By contrast, no significant
      association was seen between improvement in mood or quality of life and amount of
      home practice of coping skills.

PMID- 1997999
TI  - Factors related to cholesterol screening and cholesterol level awareness--United
      States, 1989.

PMID- 1998000
TI  - The application of behavioral procedures to childhood asthma: current and future
      perspectives.
AB  - The development and application of behavioral procedures to childhood asthma
      during the past three decades is reviewed, with particular implications for
      researchers and practitioners. In particular, the article describes two major
      categories of procedures that comprise the current state of the art of behavioral
      intervention; prevention and management of attacks and self-management by
      patients of their asthma. Much of the discussion focuses on self-management
      skills, particularly the essential ingredients of data collection, information
      processing and evaluation, steps required to manage attacks and self-reaction to
      performance. A final section of the paper speculates on the future directions of
      applying behavioral techniques to childhood asthma. The need to analyze
      individual attacks suffered by individual patients is emphasized; in addition,
      the scientific skills required to successfully manage asthma, performed both by
      medical personnel and patients, are described. It is hoped that the future will
      see these skills applied in a manner so that each attack is treated as if it were
      an experiment.

PMID- 1998001
TI  - Membrane cholesterol dynamics: cholesterol domains and kinetic pools.
AB  - Nonreceptor mediated cholesterol uptake and reverse cholesterol transport in
      cells occur through cellular membranes. Thus, elucidation of cholesterol dynamics
      in membranes is essential to understanding cellular cholesterol accumulation and
      loss. To this end, it has become increasingly evident that cholesterol is not
      randomly distributed in either model or biologic membranes. Instead, membrane
      cholesterol appears to be organized into structural and kinetic domains or pools.
      Cholesterol-rich and poor domains can even be observed histochemically and
      physically isolated from epithelial cell surface membranes. The physiologic
      importance of these domains is 2-fold: (i) Select membrane proteins (receptors,
      transporters, etc.) are localized in either cholesterol-rich or cholesterol-poor
      domains. Consequently, the structure and properties of the domains rather than of
      the bulk lipid may selectively affect the function of proteins residing therein.
      (ii) Kinetic evidence suggests that cholesterol transport through and between
      membranes may occur through specific domains or pools. Regulation of the size and
      properties of such domains may be controlling factors of cholesterol transport or
      accumulation in cells. Recent technologic advances in the use of fluorescent
      sterols have allowed examination of cholesterol domain structure in model and
      biologic membranes. These techniques have been applied to examine the role of
      high-density lipoprotein, cholesterol lowering drugs, and intracellular lipid
      transfer proteins in membrane sterol domain structure and sterol movement between
      membranes.

PMID- 1998002
TI  - Age-associated changes in antibody-forming cells (B cells).

PMID- 1998003
TI  - Interspecies variation in the cellular phase of blood fibrinolytic activity.
AB  - In normal humans, whole blood fibrinolytic activity is three to six times greater
      than that of companion plasma. This additional activity derives from neutrophil
      enzymes, with possible contributions from other cell types. Rats and dogs are
      frequently used to study fibrinolysis in animal models of human disease. Compared
      with humans, rats are relatively neutropenic, whereas dogs have a relative
      neutrophilic leukocytosis. Interspecies variation in cellular phase fibrinolytic
      activity has not been examined. We therefore determined whole blood, plasma, and
      cellular phase fibrinolytic activity in 27 rats and 6 dogs, using a 125I-fibrin
      solid phase assay. Whole blood and plasma activities were similar in rats,
      consistent with very low cellular activity. Dogs, however, had high cellular
      phase activity, making up an average 91% of whole blood activity. These results
      suggest that blood fibrinolytic mechanisms in rats differ from those in humans
      and dogs, and that this difference should be considered when studying
      fibrinolysis in models of human disease.

PMID- 1998005
TI  - Angiotensin-converting enzyme inhibition reduces neuroblastoma cell growth rate.
AB  - Because of the known capacity of angiotensin II to serve as a growth factor in
      multiple tissues, we elected to study the effects of renin-angiotensin system
      inhibition on the growth of human SH-SY5Y neuroblastoma cells. Cells were treated
      with captopril (0.05-5 mg/ml), enalapril, or enalaprilat (0.02-5 mg/ml) or
      saralasin (0.1-0.25 mg/ml). In all cases, statistically significant reductions in
      cell growth were seen over 5 days of culture. In additional experiments,
      captopril and enalaprilat significantly decreased thymidine incorporation into
      DNA in these cells. The administration of angiotensin II in the presence of
      captopril partially offset these suppressive effects.

PMID- 1998004
TI  - Effects of hypertension on aortic antioxidant status in human abdominal
      aneurysmal and occlusive disease.
AB  - The biochemical mechanisms by which hypertension accelerates atherosclerosis and
      increases the risk of aortic aneurysm rupture are poorly understood. This study
      evaluates the effects of hypertension on aortic trace element concentrations and
      antioxidant status in tissue removed from 26 normotensive (NT) and 20
      hypertensive (HT) patients. Twenty-seven of 46 patients (59%) had aneurysmal
      (AA), and 19 of 46 (41%) had occlusive disease (OD). Aortic iron concentrations
      were markedly higher in both OD and AA tissue compared with controls. A similar
      trend was observed with copper concentrations, with the highest elevations
      observed in HT AA tissues. No significant differences were observed in zinc
      concentrations, except that HT AA aorta had significantly lower zinc levels than
      either OD or control tissue. Aortic ascorbic acid concentrations in diseased
      aorta were lower than those of controls, but independent of blood pressure.
      Copper-zinc-superoxide dismutase activity was similarly reduced, with the lowest
      activity observed in diseased aorta from HT patients. Only HT AA aorta had
      significantly higher manganese-superoxide dismutase activity than controls. The
      aortas of patients with AA had significantly lower amounts of elastin and greater
      elastase activity than either controls or those with OD. However, the differences
      were independent of blood pressure. Hypertensive patients with OD and AA had 31%
      more and 27% less aortic collagen, respectively, than their NT counterparts (P
      less than 0.05). These data suggest that the reduction in aortic collagen and
      elastin in HT patients with AA compared with their NT counterparts may explain
      the larger size of aneurysms and predispose to their eventual rupture.
      Furthermore, the diminished antioxidant status associated with HT predisposes to
      lipid peroxidation, which contributes to the acceleration of these processes. Our
      studies were conducted in patients with established aortic aneurysmal and
      occlusive disease. Whether these observations are pertinent to the pathogenesis
      of AA and OD remains unclear and merits further study.

PMID- 1998006
TI  - Estradiol down-regulation of the rat uterine estrogen receptor.
AB  - We have previously shown that neonatal exposure of rats to pharmacologic doses of
      diethylstilbestrol via daily injections resulted in a significant decrease in the
      estrogen-binding capacity of the uterine estrogen receptor (ER). In this study,
      we examined the effects of physiologic and pharmacologic doses of estradiol (E2)
      administered to adult ovariectomized rats via Silastic implants. Two days after
      implantation, uteri were removed, weighted, and homogenized, and ER levels were
      determined in the supernatant (hydroxylapatite assay) and low-speed pellet
      (nuclear exchange assay). Implants containing E2 concentrations of 0.005 or 0.05
      mg/ml increased cytosolic but not total ER-binding capacity, whereas 0.5 or 5.0
      mg of E2/ml implants decreased the binding capacity of cytosol ER to 40% and
      total ER to 50% of control values. The 0.005-mg/ml dose increased cytosol ER
      without increasing uterine weight; all higher doses significantly increased
      uterine weight. Determination of ER protein by an ER radioimmunoassay showed the
      same extent of reduction of ER concentration as the binding assays, demonstrating
      that the loss in E2 binding capacity is homologous down-regulation. The down
      regulation of ER was maximal at 24 hr and was completely reversible after implant
      removal, although the time required to recover from down-regulation was dose
      dependent. Uterine weight also returned to control levels slowly after implant
      removal. Neither the sedimentation rate of the down-regulated ER nor the Kd of
      the cytosolic ER changed following long-term implantation; however, the Kd of the
      nuclear ER decreased significantly. This is the first demonstration of in vivo
      homologous down-regulation of uterine ER. ER down-regulation may play a role in
      several biologic processes.

PMID- 1998007
TI  - Metabolism of progesterone in the canine feto-placental unit.
AB  - Progesterone (P), a major hormone of pregnancy, was selected for study under the
      conditions of an intact utero-placental-fetal unit. A preparation of the canine
      gravid uterus, near term, is described and shown to permit observation of the
      metabolic relationships of the steroid hormone P between maternal and fetal
      organisms. [1,2-3H] P or [7 alpha-3H]P was injected into pups, while [4-14C]P was
      injected into the uterine circulation. Perfusion was continued for 1 hr with
      excellent survival of the pups. Identified metabolites in the fetal and maternal
      tissues suggest a metabolic pool that is shared throughout the unit.

PMID- 1998008
TI  - Absence of estrogenic activity in a diet that promotes estrous cyclicity in
      C57BL/6J mice.
AB  - A breeder diet that shortens estrous cycles in mice has been reported to contain
      estrogenic substances, based on its ability to increase uterine weight of
      immature mice. However, the estrogenicity of the diet was inferred from uterine
      weight gain of immature mice that were intact. The increased uterine weight of
      mice on the breeder diet could thus have resulted from a precocious pubertal
      increase of endogenous estrogens induced by the diet rather than estrogenic
      substances in the diet. We therefore measured the estrogenicity of the breeder
      diet in ovariectomized animals. C57BL/6J mice were fed the breeder diet or a
      standard diet for 1 or 4 weeks. The breeder diet failed to increase uterine
      weights above control values for either treatment interval. Intact mice that were
      fed the breeder diet had twice the number of cycles of mice fed the standard
      diet, a confirmation of earlier studies. These results indicate that the breeder
      diet does not contain biologically significant estrogenic activity, and thus
      potentiates cyclicity by other means.

PMID- 1998009
TI  - Ca2(+)-sensitive K+ channel in aortic smooth muscle of rats.
AB  - We measured K+ channel activity in inside-out patches of cell membrane from
      aortic vascular smooth muscle cultured (Passages 1-3) from Wistar, Wistar-Kyoto,
      and spontaneously hypertensive rats (SHR). With [Ca2+]i between 25 and 100 nm and
      150 mm K+ on both sides of the membrane, the conductance of this channel was 55
      +/- 7 pS (slope of current-voltage curve through 0 mV) and the current was
      outwardly rectified. There was no difference in single-channel conductance among
      the three rat strains. Increasing negative holding voltages or increasing
      [Ca2+]i, increased the probability of this type channel being open (Npo; P less
      than 0.01); SHR had a larger NPo (P less than 0.01). Compared with cells from
      Wistar and Wistar-Kyoto, cells from SHR also had the longest mean open time. The
      increased NPo and mean open time we observed in this K+ channel of cells from SHR
      could contribute, at least in part, to the increased membrane K+ permeability,
      reported previously.

PMID- 1998010
TI  - Oxysterols, cholesterol biosynthesis, and vascular endothelial cell monolayer
      barrier function.
AB  - A spectrum of cholesterol oxidation derivatives (oxysterols) is generated in food
      products exposed to heat or radiation in the presence of oxygen. One of these
      derivatives (cholestan-3 beta,5 alpha,6 beta-triol) was shown to compromise the
      selective barrier function of cultured vascular endothelial cell monolayers, an
      action that may initiate atherosclerotic lesion formation. This study sought to
      investigate the relationship of cholesterol synthesis inhibition by several
      naturally occurring oxysterols to depression of vascular endothelial cell
      monolayer barrier function, determined as an increase in albumin transfer across
      cultured endothelial monolayers. All oxysterols tested caused a variable time-
      and dose-dependent elevation in trans-endothelial albumin transfer, and they were
      also able to inhibit cholesterol biosynthesis to varying degrees. Pure
      cholesterol was without effect on both counts. The correlation between the
      increase in albumin transfer related to oxysterol exposure and the ability of
      oxysterols to suppress cholesterol biosynthesis was, however, poor. Moreover,
      mevinolin, a water-soluble competitive inhibitor of cholesterol synthesis,
      reduced the rate of cholesterol synthesis to 0.9% of control but did not
      significantly increase albumin transfer. Cholestan-3 beta,5 alpha,6 beta-triol
      caused a 660% elevation in albumin transfer while cholesterol synthesis remained
      at 11% of control. We conclude that changes in endothelial barrier function
      caused by exposure to the oxysterols examined, but not pure cholesterol, are
      probably related to factors other than the well-known action of cholesterol
      biosynthesis inhibition. These findings may have implications in the development
      of atherosclerosis.

PMID- 1998011
TI  - A comparison of chloride, bromide, and sucrose dilution volumes in neonatal pigs.
AB  - Use of 36Cl, 82Br, and [3H]sucrose to estimate extracellular water volume was
      evaluated in 14 piglets (7-14 days old). 36Cl and 82Br were distributed in
      approximately the same volume, but a period of 5-6 hr after injection was
      required to reach equilibrium in the neonatal pig. Dilution volumes calculated
      before equilibration (2-5 hr) for 36Cl (326 +/- 11 ml/kg) and 82Br (328 +/- 13
      ml/kg) were different from equilibration (6-8 hr) phase volumes (356 +/- 13 ml/kg
      and 355 +/- 13 ml/kg, respectively; P less than 0.001). A 3-hr sample estimated
      the same volume distribution calculated by extrapolation of the 6- to 8-hr period
      because of the relationship between the two slopes of the plasma clearance
      curves. After the 82Br and 36Cl had achieved equilibration, each was distributed
      in a volume equivalent to total body chloride space (362 +/- 29 ml/kg) measured
      by neutron activation; no statistical differences were found (P = 0.6). The early
      equilibration phase measured a 10% smaller, faster exchangeable fraction of total
      body Cl. Sucrose dilution volume (332 +/- 19 ml/kg) required multiple plasma
      samples for extrapolation and measured a dilution volume 7% smaller (P less than
      0.05) than total body chloride space.

PMID- 1998012
TI  - Relative antigenicity of components of a vascularized limb allograft.
AB  - At present, the transplantation of vascularized limb-tissue allografts can be
      achieved only with generalized host immunosuppression, which results in
      significant systemic toxicity, thereby precluding their clinical use. A better
      understanding of the immunogenic mechanisms of these allografts may permit less
      toxic and thus clinically applicable means of host immunosuppression. In this
      study, individual vascularized limb tissues (skin, subcutaneous tissue, muscle,
      bone, and blood vessels) and a whole limb were transplanted microsurgically
      across a strong histocompatibility barrier in rats. The respective cell-mediated
      and humoral immune responses generated in the hosts were determined by means of
      mixed lymphocyte cultures by radioactive 51Cr release assays and compared. No
      single tissue predominated in the elicited immune response. Rather, the various
      tissue components interacted with the host immune system in a complex but
      predictable pattern with differing timing and intensity. Surprisingly, the whole
      limb allograft elicited less immune response than did allografts of its
      individual components. The data presented here also serve as a foundation for
      further elucidation of the immunogenic mechanisms of vascularized limb-tissue
      allografts.

PMID- 1998013
TI  - Iliac versus cranial bone for secondary grafting of residual alveolar clefts.
AB  - Secondary bone grafting of the maxilla in the mixed transitional dentition stage
      has become a well-accepted procedure in the surgical protocol for rehabilitation
      of patients with residual alveolar clefts. This retrospective study was
      undertaken to evaluate and compare the long-term results obtained with iliac or
      cranial cancellous bone graft material in the area of alveolar clefts and was
      based on the independent experience of two plastic surgeons from the same center
      using exclusively cranial or iliac cancellous bone, respectively. The criteria
      for surgery were similar. The surgical technique, with the exception of the bone
      grafting material, also was similar, and all patients were treated by the same
      group of orthodontists. Fifteen patients from each group, from a total of over
      100 patients, were randomly selected and included in the study. All patients were
      followed up from 18 to 60 months. Operative and perioperative parameters, donor
      site morbidity, and long-term results were evaluated, compared, and analyzed.
      There were no significant differences between the two groups, and equally good
      results in terms of bone incorporation, tooth eruption, and appearance were
      obtained with both iliac and cranial bone grafts. We conclude from our study that
      successful bone grafting is primarily achieved by adherence to meticulous
      surgical technique, simultaneous closure of coexisting oronasal or palatal
      fistulae, use of cancellous bone particles only, and coverage of the grafts with
      well-vascularized flaps. The source of bone graft does not seem to primarily
      influence the success of the outcome.

PMID- 1998014
TI  - Early definitive bone and soft-tissue reconstruction of major gunshot wounds of
      the face.
AB  - The use of craniofacial surgical techniques, extended open reduction, rigid
      fixation with plates and screws, and the replacement of severely damaged or
      missing bone with immediate bone grafting in the treatment of complex facial
      fractures has been applied to the management of severe gunshot wounds of the
      face. Early definitive bone and soft-tissue reconstruction has been performed in
      37 patients. One-hundred and seventy-seven primary bone grafts were utilized in
      33 patients for orbital, nasal, zygomatic, and maxillary reconstruction. Twenty
      six patients required mandibular repair with compression or reconstruction
      plates. Soft-tissue reconstruction was provided by a combination of flaps. Four
      patients had extensive soft-tissue loss replaced by free vascularized omental
      flaps. The omentum provided circumferential coverage of the mandibular
      reconstruction and reconstruction of the floor of the mouth and was then tunneled
      in a circle through both cheeks into the middle and upper face. The omentum
      reconstructed deficits in the hard palate and upper buccal sulcus and was then
      wrapped around all zygomatic, orbital, and midfacial bone grafts and used to fill
      in dead space in the maxillary, ethmoid, and frontal sinuses. The omentum is not
      used to provide contour and bulk, but to cover bone grafts and plates and fill in
      dead space. Carefully shaped bone grafts provide the correct craniofacial
      scaffold. Early restoration of a midfacial bony scaffold and the prevention of
      soft-tissue contraction facilitate secondary reconstruction. Four late total
      nasal reconstructions with tissue-expanded forehead skin wrapped around bone
      grafts were performed.

PMID- 1998015
TI  - The healing of facial bone fractures by the process of secondary union.
AB  - The mechanism of healing of facial bone fractures was investigated in a rabbit
      model. Twelve New Zealand white rabbits underwent surgically induced fractures of
      the right infraorbital rim and fracture ostectomies (4 to 5 mm) of the left
      infraorbital rim. Animals were sacrificed 2, 4, and 8 weeks postfracture. Bone,
      including periosteum, obtained from each fracture or fracture osteoctomy site was
      divided longitudinally for hematoxylin and eosin staining, fluorescent
      microscopy, microangiography, and microradiography. Sequential fluorochrome
      labels of oxytetracycline (30 mg/kg), alizarin complexone (30 mg/kg), DCAF (20
      mg/kg), and xylenol orange (90 mg/kg) were administered 24 hours preoperatively
      and at 1, 2, 4, and 8 weeks postfracture. All fracture and fracture ostectomy
      sites demonstrated vascular ingrowth, mineralization, and woven bone formation by
      2 to 4 weeks postoperatively, beginning with a cartilage precursor. Subsequently,
      the woven bone was replaced with remodeled lamellar bone, resulting in complete
      bony healing by 8 weeks postoperatively. These steps were substantiated by
      microscopic, microradiographic, and radiologic examination of the specimens. This
      study demonstrates that fractures of the facial bones in a rabbit model heal by a
      process of new bone formation that resembles secondary union in endochondral
      bones.

PMID- 1998016
TI  - Selective myectomy for postparetic facial synkinesis.
AB  - Synkinetic movements are secondary to facial palsy because they appear like a
      late sequela to spontaneously healing facial nerve injury. They are produced by
      an involuntary contraction of a muscle group simultaneous with contraction of
      other homologous muscle groups. The disorderly regeneration of severed axons is
      responsible for these movements. According to the Lippschitz theory, the
      regenerating nerve fibers sprout into the wrong peripheral branches. Between 1975
      and 1986, 71 patients with facial paralysis were evaluated. Spontaneous recovery
      from the facial paralysis occurred in 28 of these patients; 14 (50 percent)
      developed synkinetic movements, and surgical treatment was sought by only 6
      patients. In all patients, the lesion of the facial nerve was in the trunk,
      proximal to the principal ramification. The most frequent clinical finding was
      simultaneous activation between the orbicularis oculi and the elevators of the
      corner of the mouth (12 patients) or the elevators of the upper lip (2 patients).
      In 8 patients, in whom the slight synkinesis was not noticed by the patients,
      surgical correction was not necessary, but in the other 6 patients with severe
      aesthetic disturbances, surgical treatment for "disconnection" of the wrong
      impulses was realized. I obtained this "disconnection" through resection of the
      involved perioral muscle groups instead of paralysis of the orbicularis oculi.
      Follow-up of the 6 patients operated with the surgical treatment proposed herein
      for between 4 and 8 years has shown good aesthetic results without functional or
      aesthetic sequelae.

PMID- 1998017
TI  - Intrapalatine resection (IPR) in the treatment of sleep apnea and snoring.
AB  - A conservative surgical technique is proposed as an alternative to the classical
      uvulopalatopharyngoplasty (UPPP) for the treatment of obstructive sleep apnea and
      snoring. The resection is strictly intrapalatine, and careful suturing in three
      planes seems to lead to complete disappearance of the often unbearable
      postoperative pain. The soft palate is shortened but nonetheless still resembles
      a normal soft palate. Uvulopalatopharyngoplasty (UPPP) was described by Ikematsu
      in 1952. This method has taken on a new lease of life in recent years. Its
      efficacy is generally accepted, and its use, especially in cases of obstructive
      sleep apnea syndrome, is the only treatment of the palatal velum at present
      practiced. In addition to aesthetic problems, this method generally gives rise to
      complications in the shape of temporary--but sometimes considerable--pain, nasal
      regurgitation, and a nasal voice. In a small percentage of patients, some of
      these disorders may prove irreversible. In my series of eight patients, five were
      obese and presented with hypertension. Three of them also were suffering from
      obstructive sleep apnea syndrome. The three others were ordinary snorers who
      caused considerable inconvenience to sleeping partners.

PMID- 1998018
TI  - Experience with 50 free TRAM flap breast reconstructions.
AB  - The data from the first 50 patients undergoing free TRAM flap breast
      reconstruction in two units were examined. Average patient age was 42 years, and
      average weight was 62 kg. Forty percent of patients were chronic smokers, and 26
      percent had low abdominal scars. Twelve percent exercised their abdominal muscles
      regularly. Eighteen percent had undergone radical mastectomy, whereas 76 percent
      had undergone modified radical mastectomy and 6 percent had undergone
      subcutaneous mastectomy. Postoperative radiotherapy had been given in 16 percent
      of patients, and 54 percent had received postoperative chemotherapy. The average
      time from mastectomy was 32 months, whereas six breasts were reconstructed
      immediately. Average operating time was 5.6 hours, and average blood loss was 2.4
      units. Average hospital stay was 11.2 days. Complications included three total
      flap losses (6 percent) and two partial flap losses (4 percent). Abdominal hernia
      occurred in two patients (4 percent).

PMID- 1998019
TI  - Methyl prednisolone in double-lumen gel-saline submuscular mammary prostheses: a
      double-blind, prospective, controlled clinical trial.
AB  - At the time of immediate breast reconstruction with submuscular implants, 76
      consecutive patients (89 breasts) were randomized into two groups. One received a
      gel-saline, double-lumen implant with 40 cc of saline added to the outer lumen,
      while the other received the same implant plus 40 cc of saline and 16 mg methyl
      prednisolone (40 mg%). Patients were followed for a minimum of 3 years. The
      groups, which were matched for patient age and implant size, were evaluated at 3,
      12, 24, and 36 months for capsular contracture, steroid atrophy, and other
      complications. With completion of the double-blind study, the patients with
      submuscular gel-saline implants with only saline added had an overall capsular
      contracture rate of 38 percent at 3 months, 38 percent at 12 months, and 44
      percent at 24 and 36 months. Those with methyl prednisolone had an overall
      capsular contracture rate of 14 percent at 3 months, and this remained unchanged
      through the end of the study. The rates of all other complications were
      comparable. Methyl prednisolone in a dose of 16 mg in 40 cc saline (concentration
      40 mg%), when used in the outer lumen of a double-lumen gel-saline implant in a
      submuscular pocket, is both safe and efficacious in reducing the risk of capsular
      contracture for a minimum of 3 years in patients undergoing immediate breast
      reconstruction with submuscular mammary implants.

PMID- 1998020
TI  - Tissue expansion in the treatment of pressure ulcers.
AB  - The authors report their experience using skin expanders in 11 patients with
      severe bed sores. The expanders, with different volumes, from 250 to 1000 cc,
      were generally overfilled using the cutaneous tonometer. In fact, with the
      information revealed by this apparatus on the skin in expansion, the authors were
      able to reduce the filling intervals without risking ulceration. In their
      experience, the results obtained were satisfactory: All patients treated achieved
      surgical recovery. The authors see a wide future for skin-expander use in
      pressure-ulcer treatment. They have a working hypothesis about using expanders to
      progressively advance sensitive skin in areas subject to ulceration. This
      hypothesis is based on the possibility of reexpanding the same flap several
      times, as has been seen in the treatment of other types of pathology.

PMID- 1998021
TI  - Pathogenesis of ischemic necrosis in random-pattern skin flaps induced by long
      term low-dose nicotine treatment in the rat.
AB  - The objectives of the present experiments were to study the effects of long-term
      low-dose nicotine treatment on skin hemodynamics, viability, and microvascular
      morphology in 4 x 10 cm dorsally based acute random-pattern skin flaps in the
      rat. In addition, the reversibility of the nicotine-induced detrimental effects
      on skin-flap viability following cessation of nicotine treatment also was
      investigated. Low-dose nicotine (0.6 mg/kg) administered twice daily and
      subcutaneously for 24 weeks significantly (p less than 0.05) decreased skin-flap
      capillary blood flow, distal perfusion, and length and area of skin viability
      compared with the saline-treated control (n = 15). However, these same parameters
      in rats (n = 15) whose nicotine treatment had been withheld for 2 weeks prior to
      skin-flap surgery were not significantly different from the control, thus
      indicating that the detrimental effects of this long-term, low-dose nicotine
      treatment were reversible. The mean plasma level of nicotine in the nicotine
      treated rats was 8.1 +/- 0.4 micrograms/dl and was within the range of plasma
      nicotine levels reported for human heavy cigarette smokers. Light and electron
      microscopic studies did not show evidence of histologic damage to the cutaneous
      microvasculature in acute random-pattern skin flaps and samples of normal
      (nonoperated) skin in nicotine-treated rats. It is concluded that long-term
      plasma levels of nicotine similar to those of heavy cigarette smokers are
      detrimental to the capillary blood flow and viability of random-pattern skin
      flaps in the rat. These deleterious effects can be avoided if skin flaps are
      raised 2 weeks after cessation of nicotine treatment. This low-dose nicotine
      treatment does not cause histologic damage to the microvasculature. Other
      pathogenic mechanisms of nicotine-induced skin flap ischemia are discussed.

PMID- 1998022
TI  - Free-tissue transfers for limb salvage utilizing in situ saphenous vein bypass
      conduit as the inflow.
AB  - Using vein grafts to bypass sclerotic and occluded arterial segments is a well
      established technique in vascular surgery. For infrapopliteal bypass, autogenous
      veins have better patency rates than synthetic grafts. Although not resolved, in
      situ bypasses seem to be better than reversed bypasses, especially for "far away"
      segments. Although the etiology is not understood, it is a well-known clinical
      finding that sclerosis affects arteries more than the veins and, as a whole, is
      more advanced in lower extremities compared with the trunk and upper extremities.
      Our experience with eight patients in whom critical soft-tissue defects were
      covered with free-tissue transfers in severely compromised lower extremities
      utilizing the in situ saphenous vein bypass as the inflow is presented.
      Simultaneous bypass and free-tissue transfers were performed in seven and delayed
      free-tissue transfer was done in one. Follow-up ranged from 6 months to 3 years.
      To date, two patients underwent amputations. Five patients are able to maintain
      bipedal ambulation. One patient is wheelchair-bound with intact lower
      extremities. In well-selected patients, this procedure may offer an alternative
      treatment to amputation. However, because of the complexity of these combined
      procedures, we strongly urge careful patient selection.

PMID- 1998023
TI  - Reconstruction of rat femoral veins with microvascular prostheses.
AB  - Synthetic conduits have not been suitable for microvascular reconstruction owing
      primarily to their high thrombogenicity. Vein replacements are the most
      vulnerable to thrombosis because of their low shear rates and low pressure.
      Experimental replacement of microvenous segments with prosthetic segments has
      shown little success. Recent technological advances in biomaterials and control
      of thrombogenesis provide the potential for success in the development of venous
      prostheses. The purpose of this study was to assess the use of nonbiodegradable
      composite polyurethane microvascular prostheses for reconstruction of rat femoral
      veins. Rat femoral venous defects of 10 mm were reconstructed with autogenous
      vein (n = 12), unprocessed plain polyurethane (n = 5), and nonbiodegradable
      composite polyurethane (n = 31). Patency was evaluated by direct observation and
      proximal venous milking tests. The patency rate of composite grafts was not
      significantly different from that of isotopic vein (p = 0.5, Fisher's exact
      test), and both had higher patency than unprocessed polyurethane (p less than
      0.01). Composite grafts were examined sequentially using light and scanning
      electron microscopy. Grafts were fully endothelialized between the first and
      third months. The neointimal, neomedial, and neoadventitial layers could be seen
      more distinctly over time. New opportunities in reconstructive microsurgery may
      be opened by microvascular prostheses that are complaint and thromboresistant.

PMID- 1998025
TI  - Someone out there loves you.

PMID- 1998024
TI  - Further experience in rehabilitation of zone II flexor tendon repair with dynamic
      traction splinting.
AB  - A review of all flexor tendon repairs in the "no man's land" performed from
      January of 1985 to June of 1987 was done to evaluate the efficacy of our method
      of rehabilitation. There were 60 fingers (57 patients) with complete laceration
      of the flexor digitorum profundus and flexor digitorum superficialis tendons in
      zone II. Fingers with phalangeal fractures, joint injuries, or significant skin
      loss were excluded. Follow-up ranged from 12 to 48 months. Rehabilitation
      consisted of a 12-week protocol using the U.S. military combined regimen of
      controlled motion. Features from the technique of controlled active extension
      against rubber band passive flexion as well as those of controlled passive
      extension and passive flexion were incorporated. The palmar pulley modification
      of Kleinert's dynamic traction splint was utilized. Strickland's total active
      motion formula was employed to determine results. The results were classified
      into the four categories of excellent, good, fair, and poor. Fifty-two fingers
      (86 percent) were rated excellent, 4 fingers (7 percent) were rated good, 1
      finger (2 percent) was rated fair, and 3 fingers (5 percent) were rated poor.

PMID- 1998026
TI  - Scalp necrosis in a neonate treated with cultured autologous keratinocytes.
AB  - A neonate compromised by a stressful labor, low birth weight, anemia, seizures,
      and enterocolitis developed necrosis of a caput succedaneum of the calvaria.
      Coverage with cultured autologous keratinocytes was successful and represents a
      treatment modality with minimal morbidity compared with conventional split
      thickness skin grafts.

PMID- 1998027
TI  - Congenital curved nail of the fourth toe.
AB  - Five cases of congenital curved nail of the fourth toe are reported. Patients
      included four males and one female; four cases were bilateral, and one was
      unilateral. There were no other significant associated anomalies of the
      extremities, and only the fourth toes were affected. The features of the
      deformity are a curved nail and hypoplasia of the soft tissue and bone of the
      distal phalanx of the fourth toe. This anomaly may be transmitted autosomally and
      is unique in that it may be of mesodermic origin.

PMID- 1998028
TI  - Composite reconstruction for chest wall and scalp using multiple ribs-latissimus
      dorsi osteomyocutaneous flaps as pedicled and free flaps.
AB  - A composite flap is presented based on the latissimus dorsi myocutaneous unit
      together with the underlying ninth to eleventh ribs. Three patients are
      presented. In two, a full-thickness chest-wall defect was present. In one, a full
      thickness scalp and cranial defect was present. Use of the composite
      osteomyocutaneous latissimus dorsi free flap as a pedicled flap in two patients
      and as a free flap in one patient resulted in successful definitive
      reconstruction in all with no complications. This procedure necessitates no
      transplantation of soft tissue prior to bone grafting to maintain local
      vascularity, so the simultaneous one-stage reconstruction of an osseous-soft
      tissue defect becomes possible easily.

PMID- 1998029
TI  - Island flap supplied by the dorsal branch of the ulnar artery.
AB  - Two cases are reported in which a fasciocutaneous island flap was employed
      supplied by the ulnaris dorsalis artery after the method proposed by Becker and
      Gilbert. The original technique has been modified by the authors, and this
      produces a better venous outflow. The vascular pedicle includes, besides the
      ascending branch of the artery and the venae comitantes, one of the superficial
      veins together with its respective subdermal band. A technique is also described
      that provides an optimal length for the vascular pedicle.

PMID- 1998030
TI  - Microvascular anastomosis: vascular cuff technique.
AB  - A technique is described for reinforcing and sealing a microvascular anastomosis
      by using a detached vessel segment as a cuff around the anastomosis. This may
      allow fewer microvascular sutures to be used. This would allow a simpler, less
      traumatic, and more rapid repair and may allow "more vessels to be repaired by
      more people."

PMID- 1998031
TI  - Sample size determination.

PMID- 1998032
TI  - Monitoring a free flap.

PMID- 1998033
TI  - Resection of obstructing inferior turbinates.

PMID- 1998034
TI  - Words to avoid.

PMID- 1998035
TI  - An historical note on endotracheal intubation.

PMID- 1998036
TI  - Correction in description of breast reduction with short L scar.

PMID- 1998037
TI  - Juvenile mammary hypertrophy.

PMID- 1998038
TI  - Interospection [sic] chirurgiae plasticae.

PMID- 1998039
TI  - Sequential compression devices for postoperative lipoplasty of the calves and
      ankles.

PMID- 1998040
TI  - Fixation of zygomatic fractures.

PMID- 1998041
TI  - Aural fixation.

PMID- 1998042
TI  - Porex smooth-walled silicone gel-filled breast implants.

PMID- 1998043
TI  - Priority of V-Y pedicle flap for resurfacing nasal supratip.

PMID- 1998044
TI  - Saucerization and skin cover for osteomyelitis: back to square one?

PMID- 1998045
TI  - Radiographic manifestations of common congenital anomalies.

PMID- 1998046
TI  - Radiographic manifestations of anomalies of the brain.
AB  - Congenital brain anomalies are classified as developmental anomalies, effects of
      teratogens, errors of histogenesis, or sequelae of infections. The imaging
      options for delineation of these anomalies are many; a basic understanding of the
      disorder is central to the effective choice of imaging modality. This review
      begins with a brief overview of embryogenesis then reviews the common congenital
      brain anomalies encountered in infants.

PMID- 1998047
TI  - Radiographic manifestations of congenital anomalies of the skull.
AB  - Congenital anomalies of the pediatric skull are caused by a diverse group of
      disorders. For the purposes of this discussion, these entities can be classified
      according to the radiographic appearance of the skull, which may be similar in a
      variety of different diseases. Enlarged parietal foramina, sinus pericranii,
      aplasia cutis congenita, anterior fontanelle dermoid, cephaloceles, and
      craniolacunia are all examples of loceles, and craniolacunia are all examples of
      calvarial defects. Although there are numerous causes for wormian bones (Table
      1), OI, cleidocranial dysplasia, congenital hypothyroidism, and hypophosphatasia
      are disorders that are commonly associated with defective ossification and the
      appearance of wormian bones. Osteopetrosis is an important example of rare bony
      dysplasias that cause sclerosis and hyperostosis of the skull. A partial list of
      other disorders causing similar radiographic findings is found in Table 2.
      Craniosynostosis results in an abnormality of skull shape. The suture(s) involved
      may be predicted by the deformed calvarial configuration. Knowledge of the growth
      and development of the skull and an understanding of the varied causes of
      congenital skull anomalies can enable the radiologist to provide the diagnosis or
      an informed differential diagnosis when confronted with a specific radiographic
      finding.

PMID- 1998048
TI  - Radiographic manifestations of congenital anomalies affecting the airway.
AB  - Congenital anomalies of the airway are generally uncommon, but a vast array of
      possibilities exists. Some present life-threatening emergencies at birth, and
      others go undiagnosed for years. Clinical symptoms are often nonspecific, and
      radiographic evaluation is frequently requested to localize and characterize the
      lesion before endoscopy, surgery, or medical management. The most common
      intrinsic congenital anomalies causing airway compromise in infants include
      choanal atresia, mandibular hypoplasia, laryngomalacia, vocal cord paralysis, and
      congenital subglottic stenosis. The radiologist must be on the alert for
      unsuspected additional anomalies involving the airway, lungs, and esophagus,
      which occur with relative frequency. Numerous extrinsic congenital masses of the
      head, neck, and mediastinum may compromise the airway. Hemangiomas,
      lymphangiomas, and teratomas are more likely to be noted at birth, whereas
      branchial cleft cysts, thyroglossal duct anomalies, and dermoid cysts frequently
      present later. Mass location and radiographic characteristics usually allow
      accurate preoperative diagnosis. Intracranial involvement by nasal or
      nasopharyngeal masses, intrathoracic involvement by lower neck mass, and
      intraspinal involvement by posterior neck mass must always be sought for
      radiographically. Persistence of respiratory symptoms after removal of such
      masses is not uncommon because tracheal deformity and laxity may take months or
      years to resolve. Recent advances in cine CT and MR imaging promise to improve
      imaging of the airway in general and in the pediatric population in particular.
      Significant limitations in imaging of the pediatric larynx remain. As a result,
      endoscopy continues to be the primary diagnostic tool for airway anomalies of
      this region.

PMID- 1998049
TI  - Bronchopulmonary and neurenteric forms of foregut anomalies. Imaging for
      diagnosis and management.
AB  - Bronchopulmonary foregut malformations encompass a great variety of anomalies
      that may arise from abnormal differentiation of the respiratory and alimentary
      tracts, abnormal separation of the two systems, or abnormal development of blood
      supply, perhaps singly or in combination, during early embryogenesis. The
      pulmonary and neurenteric forms share the common features of a pulmonary
      parenchymal opacification and/or intrathoracic mass, with the addition of
      vertebral anomalies in the instance of the neurenteric malformations. Plain
      radiographs serve as the starting point for diagnostic evaluation and sometimes
      are all that is needed; more often, though, the plain film findings suggest which
      road to follow in further imaging. No single imaging approach can be advocated
      for all patients. The lesion may be found initially, for example, on prenatal
      sonography. Ultrasonography also can establish the cystic nature of a mass and
      may help define vascular supply, although it cannot yet be said to have
      supplanted angiography's role in evaluating suspected sequestrations. For most
      intramediastinal or intrapulmonary masses without associated vertebral anomalies,
      CT will satisfactorily establish the cystic nature and should afford a reasonably
      confident preoperative diagnosis of bronchogenic cysts or type 1 or 2 cystic
      adenomatoid malformations. Type 3 cystic adenomatoid malformation, because of its
      relatively "solid" imaging characteristics, may not be diagnosed confidently by
      preoperative imaging. The finding of vertebral anomalies associated with a
      mediastinal mass especially warrants MR imaging to define intraspinal
      involvement. However, the association of vertebral or rib anomalies with apparent
      unilateral pulmonary agenesis or hypoplasia arouses suspicion of a
      bronchopulmonary foregut malformation that communicates with the gastrointestinal
      tract, and this uncommon situation calls for a barium examination. Radionuclide
      scintigraphy has an ancillary role in assessing foregut anomalies, but many
      findings from scintigraphy are relatively nonspecific and anatomic definition is
      poor. Scintigraphy may yield supportive information in cases of sequestration
      that have inconclusive findings as determined by plain radiographs and CT.

PMID- 1998050
TI  - Radiographic manifestations of anomalies of the lung.
AB  - Congenital nonvascular anomalies of the lung can be subdivided into those
      affecting the bronchial tree and those affecting parenchymal abnormalities.
      Embryologic development of the lung is briefly reviewed to facilitate an
      understanding of developmental pulmonary anomalies. Clinical, radiographic, and
      therapeutic aspects of these anomalies are discussed.

PMID- 1998051
TI  - Radiographic manifestations of anomalies of the chest wall.
AB  - Congenital anomalies of the thoracic wall in children as isolated findings are
      not particularly common. Indeed, some are so uncommon or peculiar that they
      become very puzzling to the observer. This article deals with many of these
      conditions and also with the thoracic wall as it might be used for the
      identification of various syndromes and dwarfing entities.

PMID- 1998052
TI  - Magnetic resonance imaging of congenital heart disease in the pediatric patient.
AB  - Current state-of-the-art MR imaging offers a high resolution evaluation of
      cardiac anatomy in the child with congenital heart disease. Although
      echocardiography remains the standard initial evaluation modality, MR imaging
      plays a key role in supplementing this information in the pediatric thorax.
      Although applications for this modality continue to be defined, some indications
      have become clear. The future of MR imaging promises better spatial resolution,
      faster image acquisition times, and in vivo spectroscopic capabilities.

PMID- 1998054
TI  - Radiographic manifestations of congenital anomalies of the aortic arch.
AB  - This article discusses congenital anomalies of the aortic arch. Many
      malformations of a left, right, or double aortic arch produce tracheal,
      bronchial, and esophageal compression and can be recognized on chest radiographs
      or esophagrams and confirmed by angiography, computed tomography, or magnetic
      resonance imaging. Other congenital lesions of the aortic arch are characterized
      by aortic obstruction and include supravalvular aortic stenosis, aortic arch
      interruption or atresia, and coarctation.

PMID- 1998053
TI  - Radiographic manifestations of congenital heart disease in the adult patient.
AB  - Improvements in the preoperative evaluation, surgical treatment, and
      postoperative care of patients with congenital cardiac disease have allowed a
      large patient population with congenital cardiac abnormalities to reach
      adolescence and adulthood. Noninvasive diagnostic imaging procedures (e.g., plain
      film radiography, echocardiography, computed tomography, and magnetic resonance
      imaging) are playing an increasingly important role in the evaluation and
      management of adults with both treated and untreated congenital cardiac disease.
      The role of plain film radiology is emphasized.

PMID- 1998055
TI  - Radiographic manifestations of anomalies of the gastrointestinal tract.
AB  - Congenital anomalies of the gastrointestinal tract can pose serious threats to
      the health of newborn infants and children. Perhaps nowhere has pediatric surgery
      had as dramatic an impact as in the care and treatment of these conditions. The
      pediatric radiologist works closely with the surgeon in evaluating these
      anomalies in young children. Plain radiographic films and contrast studies have
      been and remain the first step in studying these anomalies. Newer imaging
      modalities, however, also have made contributions to the continuing importance of
      the role of the radiologist in the diagnosis and care of children with these
      anomalies.

PMID- 1998056
TI  - Radiographic manifestations of renal anomalies.
AB  - Intrauterine sonography has revolutionized the detection of renal anomalies.
      Previously unavailable demonstrations of abnormalities pose a new challenge to
      those responsible for the care of these patients. Optimal management is dependent
      on knowledge of the natural history of the demonstrated abnormality, the
      sequelae, and also the results and the complications of the various forms of
      available treatment.

PMID- 1998057
TI  - Radiographic manifestations of congenital anomalies of the lower urinary tract.
AB  - The evaluation of anomalies of the lower urinary tract (ureter, bladder, and
      urethra) requires high quality ultrasonography, voiding cystourethrography, and,
      occasionally, intravenous urography and contrast sinography. Infants with these
      anomalies present because of abnormal intrauterine ultrasonographic examinations,
      urinary tract infections, or obvious external malformations. With a solid
      embryologic knowledge of the development of the lower urinary tract the
      radiologist can tailor the imaging procedures to demonstrate almost all aspects
      of the anomaly and the presence or absence of frequently associated
      malformations.

PMID- 1998058
TI  - Radiographic manifestations of anomalies of the limbs.
AB  - Limb anomalies and their commonly associated organ malformations are increasingly
      recognized in fetal life because of the use of high resolution real-time
      sonography. In most instances plain radiography establishes the diagnosis of limb
      anomalies shortly after birth. In some neonates the diagnosis is tentative until
      full skeletal maturity is attained. When evaluation of the soft tissues and
      unmineralized cartilage or ossification center is a prerequisite to early
      definitive therapy, computed tomography and magnetic resonance imaging are the
      procedures of choice.

PMID- 1998059
TI  - Radiographic manifestations of congenital anomalies of the spine.
AB  - Although the foregoing review of embryologic development and congenital anomalies
      of the spine in infants and children is necessarily brief, the most commonly
      encountered abnormalities have been reviewed, and when possible, an attempt has
      been made to cite the stage of embryologic development at which the various
      abnormalities originate. As noted, congenital abnormalities of the spine are
      relatively uncommon but may be of profound clinical significance. During the past
      decade, the most significant developments in the diagnosis and treatment of these
      abnormalities have been ultrasonography, CT scanning, and MR imaging. In the
      neonate, the spinal cord and neural outflow can be evaluated by ultrasonography
      until the osseous elements begin to fuse. Thereafter, MR imaging is the procedure
      of choice because it permits evaluation of the spine and spinal cord in all
      planes of imaging and provides detailed evaluation of the effect of osseous
      abnormalities on neural structures. Finally, plain radiographs of the spine for
      evaluation of neonates who have any of a spectrum of sacral dimples are rarely
      helpful, and in the presence of significant cutaneous or subcutaneous
      abnormalities, ultrasonography is the preferred modality for evaluation.

PMID- 1998060
TI  - Opinions on baccalaureate degrees for radiation therapists.
AB  - In 1980, a survey of chief radiation therapists assessed opinions on
      baccalaureate education for radiation therapists. Results suggested a need in
      education and administrative/management positions. Another survey in 1987
      assessed the opinions of 484 technologists regarding baccalaureate-level
      education. Results suggest that more than half support the idea and would pursue
      baccalaureate degrees. Results also indicate concerns that baccalaureate
      education could detract from clinical preparation.

PMID- 1998061
TI  - Mechanics and treatment of vasovagal syncope.
AB  - Radiologic technologists are called upon to provide patient care as well as
      produce radiographs. In accordance with quality assurance programs in health care
      institutions, we are expected to know and use accepted standard methods of care.
      This article provides the reader with background on the causes and treatments of
      vasovagal syncope. Sections include signs and symptoms, anatomy and physiology
      and common methods of treatment.

PMID- 1998062
TI  - Radiographic exposure supplement to the ACR Diagnosis Index.
AB  - The principles of radiographic exposure are not included in the American College
      of Radiology Index for Radiological Diagnoses. A supplement covering such
      information would permit consistent indexing and integration of principles of
      radiographic exposure teaching case files with the comprehensive and well
      accepted ACR anatomical and pathological index. This article proposes and
      describes such a supplement, along with an alphabetical index.

PMID- 1998064
TI  - Valuable lessons from listening.

PMID- 1998063
TI  - Apicoaortic valved conduits in a canine model.
AB  - Evaluating new developments in surgical methods and materials of aortic bypass
      prosthetics requires the use of an appropriate animal model, a well established
      surgical protocol and post surgical aortography. This article describes the
      surgical technique, post operative care and the angiographic technique used for
      an apicoaortic conduit placement in a canine model.

PMID- 1998065
TI  - Demographics are us.

PMID- 1998066
TI  - A striking density.

PMID- 1998067
TI  - Reaching the 'ho-hummers'.

PMID- 1998068
TI  - Choosing the right tools.

PMID- 1998069
TI  - Privileges denied: intracorporate conspiracy doctrine.

PMID- 1998071
TI  - Legal case briefs for nurses. S.D.: agency's liability for unemployment
      contributions; MI.: "lost opportunity to survive": CRNA involved.

PMID- 1998070
TI  - Failure to diagnose pregnancy: no pelvic exam. Case in point: Pines v. Dr. Carlos
      D. Moreno, Inc. (569 SO. 2d 203--LA (1990)).

PMID- 1998072
TI  - Failure to order biopsy for breast lump: death results. Case in point: kennedy v.
      U.S. (750 F. Supp. 206--LA (1990)).

PMID- 1998073
TI  - Role of CCK in regulation of food intake.

PMID- 1998074
TI  - Neurophysiology and neuropharmacology of hypothalamic magnocellular neurons
      secreting vasopressin and oxytocin.

PMID- 1998075
TI  - Regulation of intracellular pH. Introduction.

PMID- 1998076
TI  - [What is your roentgen diagnosis? Calcified echinococcus cyst in the upper
      abdomen. DD: fecaliths, barium-containing fecal balls following contrast
      studies].

PMID- 1998077
TI  - [Malaria prophylaxis and self-care 1990--problems and current solutions].
AB  - For successful malaria prophylaxis, future travelers need to be informed about
      the risks of infection and about systematic measures to be taken against mosquito
      bites. For visits in areas of high transmission, continuous chemoprophylaxis is
      recommended, whereas in regions with low transmission a stand-by medication for
      self-therapy is sufficient. Each of these four measures has some problems which
      are discussed here in addition to the recently published recommendations by the
      Swiss Working Group for Medical Advice to Travelers.

PMID- 1998078
TI  - [From malaria chemoprophylaxis to malaria self-treatment (1975-1989)].
AB  - Swissair's 3000-odd cockpit and cabin personnel spend an aggregate total of one
      year in the tropics for every ten years of flight service with the airline. Since
      1975, company policy has been to issue all crews with a 'treatment dose' of anti
      malaria medication to be taken if malaria contraction is suspected. Up until
      1985, this treatment dose medication was recommended to crews for cases in which
      malaria was suspected even though chemoprophylactic medication had been taken.
      Since 1985, crews have been advised to rely solely on the treatment dose (i.e.
      not take any chemoprophylactic medication) if they are exposed to only low or
      moderate malaria risk. Experience so far has been encouraging: There has been no
      increase in incidences of malaria; the approach has been widely accepted among
      crews; the treatment dose (1%) has been judiciously used; the amount of
      chemoprophylactic tablets issued has declined; the number of repellents issued
      has increased; and the fear of side-effects from anti-malaria medication has
      decreased. The risk of contracting malaria-about one case per 200 to 300 years of
      service-is accepted. The question of whether and to what extent these
      experiences, which have been recorded among a small and selected group of the
      population, can be applied to other frequent flyers merits further investigation.

PMID- 1998079
TI  - [Clinical aspects and diagnosis of malaria].
AB  - Malaria must be included in the differential diagnosis of all febrile patients.
      Malaria is classified 'complicated' or 'uncomplicated', according to clinical
      findings (cerebral malaria, generalized convulsions, pulmonary edema, severe
      anemia, hyperthermia, renal failure, haemoglobinuria, shock, spontaneous
      bleeding) and laboratory results (parasitemia greater than 5%, haemoglobin less
      than 5 g%, creatinine greater than 265 mumol/l, glucose less than 2.2 mmol/l,
      DIC, pH less than 7.2, bilirubin greater than 50 mumol/l). Plasmodium (P.) vivax,
      P. ovale and P. malariae cause uncomplicated disease as a rule, whereas P.
      falciparum may result in either of both. Complicated falciparum malaria is always
      at risk for a lethal outcome. Only microscopic evidence of malaria parasites
      proofs the diagnosis. The thick smear is good for screening, thin films are
      necessary to determine the species. Serology and cultures are not helpful in
      diagnosing acute malaria. Tests for drug resistance await to be applicable for
      emergency situations.

PMID- 1998080
TI  - [Possibilities and limitations of malaria therapy in general practice].
AB  - Malaria infections by Plasmodium (P.) vivax. P. ovale or P. malariae follow
      mostly a benign course, and ambulatory treatment is safe, provided there is no
      other significant morbidity. Ambulatory treatment for falciparum malaria must be
      considered only if a number of conditions are met, making potential complications
      most unlikely. Furthermore, it is imperative that the patient can be reliably
      supervised at home. Taking into account the increase of P. falciparum strains
      resistant to chloroquine, cases meeting the criteria for ambulatory care can
      mostly be treated with mefloquine, pyrimethamine/sulfadoxine or
      pyrimethamine/sulfadoxine/mefloquine. Chloroquine remains the first choice for
      treatment of malaria due to P. vivax, P. ovale or P. malariae.

PMID- 1998081
TI  - [Current drugs for the treatment of tropical malaria].
AB  - The occurrence in the early 60's of stable resistance to chloroquine among
      Plasmodium falciparum strains in the Amazonas and on the Thai-Cambodian border
      has been a shock for all malariologists. This led to the search for new
      antimalarials without cross resistance with chloroquine. For each new drug, one
      of the major concerns was to define how rapidly parasites would develop
      resistance to this compound. Drug combinations were taken into consideration so
      as to achieve a delay in the appearance of resistance. The decision to test a
      triple combination has led to the development of Fansimef, a fixed combination
      with tablets containing 250 mg mefloquine, 500 mg sulfadoxine and 25 mg
      pyrimethamine. A very relevant delay in the development of resistance was found
      both in-vivo--in the P. berghei model--and in-vitro using P. falciparum. Fansimef
      has also been under investigations for malaria. Controlled clinical trials were
      performed in Africa, South America and South East Asia. The documentation for
      this new indication will be submitted to registration authorities in 1991. A
      preference alternative to continuous chemoprophylaxis is stand-by malaria
      treatment for travellers to regions where the malaria risk is relatively low.
      Stand-by treatment is under investigations in France and in Switzerland. In the
      search for alternative remedies against drug resistant P. falciparum malaria our
      attention was directed to Yingzhaosu, a new sesquiterpene peroxide of plant
      origin from traditional Chinese medicine. A short and convenient synthesis of
      this ring system gave access to a variety of structural analogues of
      Yingzhaosu.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1998083
TI  - [Bibliographic review (II). The application of teledocumentation and CD-ROM].

PMID- 1998082
TI  - [Malaria study].
AB  - Compliance with malaria prophylaxis or reserve drugs was investigated in 477
      individuals travelling to regions with endemic malaria. Correct intake of
      prophylactic medication was confirmed in 225 out of 285 (= 78%). Compliance was
      independent of type of drug (Mefloquine, Sulfadoxine-Pyrimethamine, Chloroquine).
      Two tourists missed to start prophylaxis one week before the onset of their
      travel. 14 travellers stopped prophylactic medication too early after their
      return, 31 tourists took too high doses of mefloquine. None of the tourists
      travelling to countries with a therapeutic reserve only became sick, whereas two
      travelling to Africa contracted malaria.

PMID- 1998084
TI  - [Nursing intervention in arterial hypertension].

PMID- 1998085
TI  - [Cystic fibrosis in newborn and nursing infants].

PMID- 1998086
TI  - [The dossier of care. An experimental analysis].

PMID- 1998087
TI  - [Multiple sclerosis: an illness plagued with uncertaincies?. Interview by M. J.
      Nadal].

PMID- 1998089
TI  - [The nurse confronting aggressiveness and violence].

PMID- 1998088
TI  - [Nursing education in the European Economic Community].

PMID- 1998090
TI  - [The efficacy of nutritional intervention in patients diagnosed with AIDS. A
      study].

PMID- 1998091
TI  - [Taking the arterial pressure].

PMID- 1998092
TI  - [New technologies in health].

PMID- 1998093
TI  - [Continuing education. 55. Subject: medical-surgical. Topic: Caring for patients
      with digestive changes].

PMID- 1998094
TI  - [Prenatal diagnosis of cervico-facial malformations and tumors].
AB  - In populations at risk or, more often, fortuitously during routine examination,
      ultrasonography makes it possible to diagnose a fairly large number of facial
      abnormalities. The most frequent of these are microphtalmos, hypotelorism (often
      as part of holoprosencephaly), hypertelorism and cleft lip. It these
      abnormalities can be isolated, they may belong to various polymalformative
      syndromes. Cervicofacial tumours can also be detected, but in utero their
      histological type can only be suspected and the possibility of surgical treatment
      is difficult to evaluate.

PMID- 1998095
TI  - [The normal mouth in newborn infants].
AB  - The mouth is the place where the newborn begins his experience of life. An
      anatomical study of the mouth and of the airways-digestive tract junction can
      explain the particular physiological features of suction and deglutition. These
      functions bear witness to the neonatal brainstem maturation, improve the
      newborn's waking state and are the sources of novel acquisitions in the field of
      interrelations between mother and child.

PMID- 1998096
TI  - [Examination and management of facial malformation].
AB  - Facial malformations are embryonic morphological accidents involving the
      prosencephalic frontonasal process (facial cleft), the branchial arches
      (laterofacial malformations) or the rhombencephalic process. Knowing the future
      development of these clusters of cells helps in the search for neurological brain
      abnormalities associated with facial cleft and the respiratory, cardiac,
      gastrointestinal and brainstem malformations associated with laterofacial
      malformations and Pierre Robin syndrome. Taking care of the newborn already in
      the maternity unit prevents the consequences of vital distress and enables the
      child to be placed under conditions of normal psychomotor development.

PMID- 1998097
TI  - [Labio-maxillary and velopalatine clefts. Clinical and therapeutic aspects].
AB  - Harelip, facial cleft and cleft palate are frequent accidents of facial
      development. There is nothing special with their embryological mechanism, but
      their consequences concerning the future anatomy of the oral and nasal cavities
      are impressive. Owing to a better understanding of facial embryology and of the
      anatomical repercussions of the clefts, satisfactory morphological results can be
      obtained by surgical lip repair performed with an ever increasing precision.

PMID- 1998098
TI  - [Pierre Robin syndrome].
AB  - During the last few years, our knowledge of Pierre Robin syndrome has benefited
      from advances in embryonic neurobiology. It has been shown that the syndrome is
      related to an anomalous development of the foetal brainstem. A multidisciplinary
      study makes it possible to value prospectively the various anomalies with which
      it may be associated and to decide on a coherent treatment. This type of
      management should reduce the mortality and prevent the sequelae of Pierre Robin
      syndrome.

PMID- 1998099
TI  - [Morphological accidents other than labio-maxillary clefts].
AB  - In neonates and infants facial and/or craniofacial involvement occurs in a large
      number of malformative syndromes the pathogenesis of which is obscure in most
      cases. This, added to clinical polymorphism, hinders all attempts at
      classification. However, chromosomal aberrations, as demonstrated by karyotype
      analysis, can be distinguished from other congenital conditions where the
      predominant site of the anomaly may help clinicians in their research. Thus,
      among congenital syndromes of probable genetic origin, the author studies those
      that are most frequent or most characteristic, i.e. craniostenosis (or
      craniofaciostenosis) with its neurocerebral risk; lesions that are predominant in
      the upper part of the face (osteochondrodysplasia, systematized
      neurocristopathies); lesions affecting mainly the lower part of the face
      (bilateral and unilateral mandibular lesions) and anomalies of the tongue. Among
      syndromes of epigenetic origin, only alcoholic embryofoetopathy is presented.
      Diagnosing such morphological accidents does not only suggest possible cranial
      and/or dentofacial therapeutic measures, sometimes applied at an early stage, but
      it also enables clinicians to inform, whenever possible, the parents on the
      potential genetic risk.

PMID- 1998100
TI  - [Tumors and tumor dysplasias of the mouth in thr newborn infant].

PMID- 1998101
TI  - [The face of the newborn infant. For the practitioner...].

PMID- 1998102
TI  - [Anti-phospholipid antibody syndrome].

PMID- 1998103
TI  - [Lithium ... 30 years later].

PMID- 1998104
TI  - [Current treatment of postoperative digestive fistula].

PMID- 1998105
TI  - [Disseminated sclerosis. Epidemiology, physiopathology, diagnosis, course,
      prognosis, principles of the treatment].

PMID- 1998106
TI  - [Development of the face in the embryo].
AB  - The facial complex and the brain develop separately from a common embryonic
      structure called ectoblast. The neural crest cells which migrate early on from
      the neural groove differentiate into facial parenchyma, so that the embryological
      origin of the face is a neural one. The cephalic pole has a primitive
      encephalofacial and encephalocervical segmentation with strict topographical
      correspondence: the nasofrontral and premaxillary structures are related to the
      anterior brain, whereas the maxillo-mandibular and anterior cervical structures
      are related to the brainstem and its nerves. Thus the face is a qualitative,
      quantitative and topographical marker of the central nervous system. At the
      beginning of the third month the embryo becomes a foetus due to the appearance of
      the first oral and pharyngeal motor sequences which are dependent upon the
      neurological development of the brainstem. This sum of embryological knowledge
      has clinical semiological applications: the face and its functions play the
      predictive role in the search for associated malformations of the same neural
      origin (brain, eye, neck, thorax). Such malformations are neurocristopathies.

PMID- 1998107
TI  - [Epidemiology of contagious diseases. Methods of surveillance, notification,
      investigation of outbreak in a community and preventive measures].

PMID- 1998108
TI  - [Post-partum monitoring breast feeding, breast abscess, phlebitis, metrorrhagia,
      renewal of menses].

PMID- 1998109
TI  - [Pulmonary tuberculosis and primary tuberculous infection. Epidemiology,
      diagnosis, course prognosis, treatment, prevention].

PMID- 1998111
TI  - Caltech deals with fraud allegations.

PMID- 1998110
TI  - [Antibiotics. General data about modes of action and mechanisms of resistance].

PMID- 1998112
TI  - Down to the bone: east German science gets cut.

PMID- 1998113
TI  - Researchers protest user fees at national labs.

PMID- 1998114
TI  - Do we need more Ph.D.s, or is fewer really better?

PMID- 1998116
TI  - Don't underestimate the nose.

PMID- 1998115
TI  - Using immunity to block conception.

PMID- 1998117
TI  - Prion proposal proved?

PMID- 1998118
TI  - Monkey see, monkey do.

PMID- 1998119
TI  - The evolution of sex chromosomes.
AB  - Structurally distinct sex chromosomes (X and Y) are the most familiar mode of
      genetic sex determination and have evolved independently in many different taxa.
      The evolutionary paths by which their characteristic properties may have evolved
      are reviewed. These properties include the failure of X and Y to recombine
      through much or all of their length, the genetic inertness of much of the Y
      chromosome, dosage compensation of the activity of X chromosomal loci, and the
      accumulation of repeated DNA sequences on the Y chromosome.

PMID- 1998120
TI  - Molecular analysis of protein assembly in muscle development.
AB  - The challenge presented by myofibril assembly in striated muscle is to understand
      the molecular mechanisms by which its protein components are arranged at each
      level of organization. Recent advances in the genetics and cell biology of muscle
      development have shown that in vivo assembly of the myofilaments requires a
      complex array of structural and associated proteins and that organization of
      whole sarcomeres occurs initially at the cell membrane. These studies have been
      complemented by in vitro analyses of the renaturation, polymerization, and three
      dimensional structure of the purified proteins.

PMID- 1998121
TI  - Direct observation of global protein motion in hemoglobin and myoglobin on
      picosecond time scales.
AB  - Picosecond phase-grating spectroscopy is highly sensitive to density changes and
      provides a new holographic approach to the study of protein dynamics.
      Photodissociation of carbon monoxide from heme proteins induces a well-defined
      transition from a ligated to a deoxy structure that is important to hemoglobin
      and myoglobin functionality. Grating spectroscopy was used to observe protein
      driven density waves on a picosecond time scale after carbon monoxide
      dissociation. This result demonstrates that global tertiary structure changes of
      proteins occur on an extremely fast time scale and provides new insight into the
      biomechanics of deterministic protein motion.

PMID- 1998123
TI  - Linking people with AIDS in rural communities: the telephone group.
AB  - People with acquired immune deficiency syndrome (AIDS) living in rural areas have
      difficulty obtaining needed information and support. Bringing support groups into
      the homes of rural residents through telephone conference call technology is an
      innovative practice strategy to address this problem. The authors describe the
      development, implementation, and evaluation of a model program consisting of six
      telephone group sessions. The goals of the psychoeducational group were to
      increase information and social support, reduce feelings of isolation, and
      enhance individual coping with living with AIDS.

PMID- 1998122
TI  - Characterization of a dimerization motif in AP-2 and its function in heterologous
      DNA-binding proteins.
AB  - The mammalian transcription factor AP-2 is a retinoic acid inducible sequence
      specific DNA-binding protein that is developmentally regulated. In this report,
      the functional domains necessary for AP-2 DNA binding were studied. AP-2 required
      a dimerization domain and an adjacent region of net basic charge to achieve a
      sequence-specific protein:DNA interaction. The sequences responsible for
      dimerization consisted of two putative amphipathic alpha helices separated by a
      large intervening span region. This helix-span-helix (HSH) domain was unable to
      bind DNA when separated from the basic region, but was still capable of
      dimerization. The ability of the HSH domain to function as a module that promotes
      DNA binding through dimerization was further demonstrated by attaching it to the
      heterologous basic region of the c-Jun proto-oncogene product. The resulting
      chimeric protein specifically recognized an AP-1 DNA-binding site in the absence
      of an intact c-Jun leucine repeat and in a manner that was dependent on the
      presence of a functional AP-2 dimerization domain.

PMID- 1998124
TI  - Women and HIV disease: an emerging social crisis.
AB  - Women are the fastest growing category of people with AIDS in the United States,
      yet this fact has been consistently ignored in the social work literature. Social
      workers' expertise is needed to curtail the escalating social crisis of women
      with HIV disease. This article addresses the major social issues faced by women
      with HIV disease and explores gender differences in HIV transmission, disease
      progression, and diagnosis. The author discusses the ways in which women's
      sexuality and reproductive rights are affected. Specific issues are examined
      regarding HIV-infected women who use intravenous drugs, women of color,
      prostitutes, and lesbian and bisexual women. The implications for the social work
      profession are discussed, and social workers in the AIDS arena and all concerned
      about HIV-infected women are urged to address this problem on an individual as
      well as a community level.

PMID- 1998125
TI  - Where do we go from here?

PMID- 1998126
TI  - Social workers' knowledge about AIDS: a national survey.
AB  - A study was conducted to assess social workers' knowledge about human
      immunodeficiency virus (HIV) infection. A questionnaire was mailed to a random
      sample of 500 members of the National Association of Social Workers in July 1988.
      Three hundred seventy-nine (75.8 percent) members responded, and limited
      demographic comparisons indicated that the sample was representative of the
      association's membership. Results showed that social workers have much to learn
      about acquired immune deficiency syndrome (AIDS); less than half the questions
      were answered correctly. Respondents had the most information about transmission
      of the virus and the least information about the impact of the epidemic on
      specific populations. Of particular concern was the small number of respondents
      who reported that they had professional reasons for being knowledgeable about
      AIDS, given the pervasive nature of the AIDS epidemic and every social worker's
      professional responsibility to be knowledgeable about HIV infection.

PMID- 1998127
TI  - AIDS-related training in U.S. schools of social work.
AB  - This article presents the results of a survey of 70 master of social work (MSW)
      programs to determine the extent and manner in which educational curricula
      include instruction on acquired immune deficiency syndrome (AIDS). Most programs
      offer students training in foundation areas pertinent to AIDS, including health
      and mental health systems, practice with racial and ethnic minorities, and
      substance abuse prevention and treatment. However, over 40 percent of programs
      provide no training in such key areas as human sexuality and primary prevention.
      Less than 15 percent of programs offer courses specific to AIDS, although a third
      of programs have incorporated AIDS content into other courses. Between 20 percent
      and 30 percent of MSW programs offer little or no attention to AIDS in their
      curricula. Implications of these findings are discussed.

PMID- 1998128
TI  - Family members' willingness to care for people with AIDS: a psychosocial
      assessment model.
AB  - This article presents a model for assessing psychosocial factors that influence
      family members' willingness to care for people with acquired immune deficiency
      syndrome (AIDS). Factors that may influence willingness to care include caregiver
      resources and coping characteristics, the degree to which the person with AIDS is
      held accountable for the illness, perceived adequacy of social support, familial
      obligation and affection, fears of acquiring the human immunodeficiency virus,
      perceptions of self-efficacy, acceptance of homosexuality, and family stigma
      resulting from the high-risk profile of people with AIDS. Implications for
      service planning and delivery are discussed.

PMID- 1998129
TI  - AIDS, social work, and the "duty to protect".
AB  - This article discusses social workers' obligations in cases where clients with
      acquired immune deficiency syndrome (AIDS) pose a threat to a third party.
      Emphasis is on cases where a client diagnosed with AIDS withholds that
      information from a sexual partner. Legal and ethical issues concerning the limits
      of confidentiality and the social worker's "duty to protect" third parties are
      reviewed. Relevant case law and emerging ethical standards in various professions
      are summarized. The author reviews legal precedents concerning disclosure of
      confidential information without a client's permission and discusses their
      relevance to AIDS cases. Implications and guidelines for social workers are
      outlined.

PMID- 1998131
TI  - Stigma management and gay identity development.
AB  - Disclosure of homosexuality is now generally viewed in the professional
      literature as more desirable than secrecy; disclosure is often seen as evidence
      of a healthy gay identity, whereas secrecy has come to be viewed as socially and
      psychologically problematic. By drawing on data from an interview study of 38 gay
      men in Montreal, this article shows that decisions concerning disclosure and
      secrecy are related to a variety of situational and relational factors that are
      largely distinct from gay identity development. It is argued that the new models
      of identity formation fail to recognize adequately the social factors that shape
      the ways gay men manage information concerning their sexual preferences.
      Conceptual and clinical implications of new normative views of disclosure and
      secrecy are discussed.

PMID- 1998132
TI  - Survival modes for people with AIDS in groups.
AB  - Four modes of positive survival with AIDS are described and analyzed as they
      appear in support groups for people with AIDS. The beneficent, artistic
      spiritual, heroic, and rational-instrumental survival modes are seen as
      compromise solutions to the twin fears of life and death described by Rank. This
      analysis is a nonpejorative means of validating group members' efforts to deal
      with the wounds and challenges of disease.

PMID- 1998130
TI  - Affective and behavioral responses of gay and bisexual men to HIV antibody
      testing.
AB  - Fifty-six gay and bisexual men were tested for antibody to the human
      immunodeficiency virus. Twenty-two subjects who tested positive, 22 subjects who
      tested negative, and 12 subjects who chose not to learn the test results were
      surveyed by questionnaire after one week and after about six months after
      testing. Subjects who tested positive and those who tested negative were also
      compared two weeks after learning results. Subjects who tested positive
      experienced an increase in anxiety, depression, and AIDS anxiety, and subjects
      who tested negative experienced a decrease in these feelings after learning
      results. Subjects who did not learn the results of their tests experienced no
      change in these feelings. All three groups altered their sexual behavior.
      Subjects were more likely to tell test results to lovers and to regular sexual
      partners than to casual sexual partners. Implications for social work practice
      are discussed.

PMID- 1998133
TI  - Physicians and the difficult patient.
AB  - Despite almost universal client contact with physicians, social workers have paid
      little attention to the nature of the physician-patient relationship and its
      impact on the quality of health care received by their clients. A central concern
      is the quality of care received by individuals defined by their physicians as
      "difficult" patients. This article examines physicians' emotional reactions to
      patients and reviews recent medical literature regarding the role of those
      reactions in the labeling of the difficult patient. The labeling of a patient as
      difficult is conceptualized as a relationship problem between physician and
      patient. Implications for social worker efforts to humanize this relationship are
      explored, and strategies for increasing social worker collaboration with
      physicians are presented.

PMID- 1998135
TI  - Caseworkers should strike a balance.

PMID- 1998134
TI  - Clinical dimensions of discharge planning with the person with AIDS.

PMID- 1998136
TI  - Many agencies were guilty of "placing out" children.

PMID- 1998137
TI  - Another group approach for adults molested as children.

PMID- 1998138
TI  - Cuba is not a healthy democracy.

PMID- 1998139
TI  - Is DNA methylation of X chromosome genes stable during aging?

PMID- 1998140
TI  - Isolation of a mutant of Chinese hamster ovary cells with defective secretion of
      a subset of secretory proteins.
AB  - The secretory pathway of mammalian cells involves a complex sequence of steps
      beginning with the translation and translocation of proteins across the rough
      endoplasmic reticulum membrane followed by their transport through a variety of
      intracellular compartments. Understanding the cellular mechanisms involved in
      protein transport would be facilitated by the application of somatic cell
      genetics techniques. Therefore, we have developed a procedure for the isolation
      of Chinese hamster ovary cell lines that are deficient in this pathway. Mutant
      (sec) clones that secrete into the medium a lesser amount of newly synthesized
      protein relative to wild type are detected in the screen. One of the sec cell
      lines, LEH6, has similar growth and protein synthetic rates as do wild-type
      cells. The extent of total protein secretion is 60-70% of wild-type with some
      proteins more reduced than others. Immunoprecipitation studies indicate that for
      LEH6 cells there is impaired secretion of fibronectin (three- to fourfold) and
      major excreted protein (two- to sixfold).

PMID- 1998141
TI  - DNA methylation of two X chromosome genes in female somatic and embryonal
      carcinoma cells.
AB  - The extent of methylation of DNA sequences upstream and within the two X-linked
      genes, Pgk-1 and Hprt, was analyzed in male and female somatic cells and in
      female embryonal carcinoma cells carrying either two active X chromosomes (Xa) or
      one active and one inactive X chromosome (Xi). Sites upstream and within the
      first intron of both Pgk-1 and Hprt were heavily methylated on the Xi in somatic
      cells and in embryonal carcinoma cells with an Xi. Reactivation of this Xi was
      accompanied by extensive demethylation of these sites. In female embryonal
      carcinoma cells with two active X chromosomes, one X inactivates during
      differentiation in culture; however, methylation did not occur during
      differentiation, consistent with the idea that DNA methylation does not play a
      role in the initiation of X inactivation but may be involved in maintaining
      inactivation of those genes on the Xi.

PMID- 1998143
TI  - Overview of surgery: 1991.

PMID- 1998142
TI  - A very large spontaneous deletion at aprt locus in CHO cells: sequence
      similarities with small aprt deletions.
AB  - Spontaneous deletion mutants can be isolated from CHO cell lines heterozygous at
      the adenine phosphoribosyltransferase locus at frequencies up to 10(-4), i.e.,
      about 100-fold higher than spontaneous point mutations. Indirect evidence has
      suggested that most deletions were in the megabase range. We have fully
      characterized one such mutant, Del 155, and shown that it resulted from an
      illegitimate recombination that took place between overlapping tetranucleotides.
      Comparisons with sequences of other deletions at various loci revealed a number
      of similarities, most striking of which was a CHI-like motif found within 6 bp of
      the upstream breakpoint of Del 155 and breakpoints of 8/21 previously described
      short deletions at the CHO aprt locus. Homology also existed between the
      downstream breakpoint of Del 155 and breakpoints of retinoblastoma gene deletions
      (3/6 cases) and also a 20-bp stretch of an Alu sequence in which breakpoints at
      the low-density lipoprotein receptor locus have been shown to cluster. The
      magnitude of the deletion event in Del 155 was assessed by pulsed field (PF) gel
      analysis and found to be at least 2100 kb long. PF analysis also indicated that
      the downstream breakpoint was near a region of structural differences between the
      two chromosomes carrying apart. These structural differences were probably not
      implicated in the mechanism of the high frequency event, since no indication of
      breakpoint clustering among a large collection of mutants was found either by
      conventional or PF electrophoretic analyses.

PMID- 1998144
TI  - Management of acute calculous cholecystitis.

PMID- 1998145
TI  - Deep venous thrombosis: recent advances in pathogenesis and treatment.

PMID- 1998146
TI  - Techniques for endoscopic obliteration of esophageal varices.
AB  - Endoscopic treatment is widely accepted for both initial and subsequent
      definitive therapy in patients with hemorrhage from esophageal varices.
      Endoscopic sclerotherapy, once performed with rigid endoscopes in anesthetized
      patients, is now performed with flexible endoscopes in awake patients, who
      frequently return home immediately after the procedure. Such treatment does not
      confer a survival advantage in the early period after variceal hemorrhage, but
      serial treatment does result in a lower risk of recurrent hemorrhage and probably
      prolongs life. Primary treatment by endoscopic sclerotherapy appears to be equal
      or more effective than primary shunt therapy, even with a sclerotherapy failure
      rate of from 10 to 30 percent. In spite of such results, the incidence of
      rebleeding and treatment-related complications and the mortality among
      sclerotherapy-treated patients remain high. Newer forms of endoscopic treatment
      such as polymer injection and mechanical ligation have emerged in attempts to
      better the results obtained with sclerotherapy. Refinement of the technique for
      conventional sclerotherapy and the potential for increased effectiveness of the
      new techniques may yet result in improved and safer endoscopic therapy for
      bleeding esophageal varices.

PMID- 1998147
TI  - The current status of the management of civilian injuries to the colon.

PMID- 1998148
TI  - Intracranial monitoring in patients with head trauma.
AB  - The treatment of head-injured patients has over the past 15 years become
      significantly more complex and involved. The rising interest in the treatment of
      these patients has been driven in large part by the growing body of evidence
      showing that there is a definite association between elevated ICP and increased
      mortality and long-term morbidity. The effective treatment of intracranial
      hypertension with hyperventilation, osmotic agents, and barbiturate therapy has
      been aided by the regular use of ICP monitoring in most neurosurgical centers. A
      continuing and ongoing record of ICP allows for the judicial and appropriate use
      of modern treatment modalities.

PMID- 1998149
TI  - Current status of the surgical treatment of melanoma.

PMID- 1998150
TI  - Operative ultrasound: ten years of experience.

PMID- 1998151
TI  - Gallstone lithotripsy.
AB  - ESWL, in its present state of technology, is unlikely to displace endoscopy as
      the treatment of first choice for common duct stones present after
      cholecystectomy, since endoscopic sphincterotomy is necessary to enhance passage
      of stones from the ductal system. However, when endoscopy fails, ESWL may prove a
      useful adjunctive treatment for both choledocholithiasis and intrahepatic stones.
      ESWL for gallstones is currently an evolving treatment option for patients with
      symptomatic gallstones. On the basis of data presented, its efficacy for
      fragmenting stones seems established, as does its safety using current
      guidelines. There is a high rate of success in patients with one or several small
      cholesterol gallstones. Although definitive proof has yet to be established, it
      is widely believed that the use of adjuvant bile salt therapy is essential for
      improving the clearance and dissolution of fragments resulting from ESWL. ESWL
      for gallstones, of all the nonsurgical treatments, seems to have the greatest
      advantage as an alternative to surgical intervention since it is the least
      invasive and can be performed in the ambulatory setting. In comparing ESWL to
      cholecystectomy, it holds the potential major advantages of being an outpatient
      treatment, keeping time off from work to a minimum, and being extremely well
      tolerated by and much less painful for a patient. Its major disadvantages at this
      time include its applicability to only a small segment of the patients with
      gallstones. Like all other nonsurgical treatments, it is also not a definitive
      treatment of gallstones, recurrent stone formation rates possibly being as high
      as 50 percent or more within 5 years of treatment. In today's scheme of health
      care delivery, the use of ESWL may ultimately depend on the willingness of the
      public or health care system to bear the additional costs of multiple treatments
      of gallstones during a person's lifetime as opposed to one definitive operation
      with its associated discomforts and temporary disability. The emergence of ESWL
      for treating gallstones has resulted in a not unexpected criticism, though
      probably a healthy criticism from the surgical community in general. However, as
      emphasized in a recent editorial, we surgeons owe it to our patients to be
      prepared to offer the best suitable treatment for their condition. ESWL in its
      present state may be that treatment for only a few patients with gallstones, but
      advancing technology could increase its applicability. Surgeons should therefore
      continue to lead by knowing how to use lithotripsy to treat cholelithiasis.

PMID- 1998153
TI  - Evolution of the laws governing dental practice: a drama in five acts.

PMID- 1998152
TI  - Palato-gingival grooves: hidden etiologic factors of periodontitis.
AB  - Palato-gingival grooves are developmental anomalies of maxillary incisors which
      contribute to severe localized periodontitis and loss of anterior teeth. Because
      these grooves or their root extensions are covered by periodontal tissues, they
      are easy to overlook as etiologic factors. This article describes palato-gingival
      grooves and discusses their prevalence, diagnosis, and treatment.

PMID- 1998154
TI  - The AIDS virus by any other name is still deadly.

PMID- 1998155
TI  - Confidentiality, privilege, and release of medical records under a subpoena duces
      tecum.
AB  - A physician's medical practice includes creating, maintaining, and releasing
      medical records. Such medical records can be an essential element in a civil
      lawsuit brought by or on behalf of a patient. Questions regarding their proper
      release under a subpoena duces tecum presented by a medical records collection
      company comprise one of the largest categories of inquiries the Texas Medical
      Association's Office of the General Counsel receives. (A subpoena duces tecum is
      a written court order commanding a person to produce in court certain designated
      documents or other evidence.) This article reviews the rules of evidence and
      civil procedure relevant to the release of medical records under a subpoena duces
      tecum in a civil case. It includes a suggested form for use by physicians when
      presented with a subpoena duces tecum by a records collection company.

PMID- 1998156
TI  - Medicine meets politics in the 72nd Texas Legislature.
AB  - Experts predict that legislative redistricting and budget stretching will
      dominate the 72nd session of the Texas Legislature, convening January 8 in
      Austin. In the midst of those debates, Texas physicians will mount an all-out
      effort to push health-related issues to the top of the lawmakers' agenda. Most
      important among those issues is restoring access to health care and health
      insurance. Here's a look at what happens when medicine meets politics.

PMID- 1998157
TI  - Lawmaking at its best, with help from TMA.

PMID- 1998158
TI  - HIV symposium will cover advances in diagnosis and management.

PMID- 1998159
TI  - Update: insulin 1991.

PMID- 1998160
TI  - Medical ethics in Texas: concepts, issues, and resources.
AB  - Ethical issues pervade medicine, and no practicing physician can avoid them. The
      physician must be able to recognize ethical issues in his practice, analyze them
      critically, and resolve them properly. Because these issues will arise even more
      frequently and become even more complex in the 1990s than before, Texas Medicine
      is devoting the Journal sections in its January and February editions to ethical
      issues in medical practice. This opening article outlines the factors
      exacerbating medical ethics issues in recent decades, describes the medical
      ethics teaching and research programs in Texas, and introduces the other articles
      in the series.

PMID- 1998161
TI  - Medical ethics reflected in codes of ethics: the Hippocratic Oath and the 1980
      AMA code compared.
AB  - The Hippocratic Oath and 1980 Code of Ethics of the American Medical Association
      (AMA) are compared to evaluate the nature of the relationship between students
      and teachers of medicine and the ethical injunctions that guide practice and make
      up the essence of the Hippocratic Oath. Such injunctions include the need to take
      care that harm is not done, to maintain confidentiality, and to avoid acts
      leading to death. The AMA code is analyzed from the perspective of its
      injunctions to give competent and compassionate care, to follow the law, to be
      responsible for guarding patients against incompetent physicians, and to assure
      that patient care is based on principles of compassion and skill. The centrality
      of trust in the relationship between patient and doctor as a crucial value in
      defining a profession is emphasized.

PMID- 1998162
TI  - But are they listening?

PMID- 1998164
TI  - Medical advertisement--let the buyer beware.

PMID- 1998163
TI  - Hib vaccine is available and soon to be required.

PMID- 1998165
TI  - Religion and medicine: interfaces that matter.
AB  - Positive relationships exist between medicine and religion. Three elements upon
      which religion and medicine interface are reverence and awe, power, and
      particularity. Implications of each of these areas and their pertinence in
      medical decision making are illustrated. Basic ethical issues are seen to rest on
      religious presuppositions, often unacknowledged. The supportive and critical
      tension between medicine and religion is important and renewing for both
      disciplines.

PMID- 1998166
TI  - Medical practice as a public trust.
AB  - Medicine as a profession is entrusted with the responsibility to prevent disease
      and treat the sick--a responsibility that has both personal and social
      dimensions. The profession's social conscience is being called upon anew as
      Americans devise an ethic of the common provision of health care.

PMID- 1998167
TI  - Assisting impaired nurses: things an employer should know.

PMID- 1998168
TI  - Leadership. Listening is key.

PMID- 1998170
TI  - [Modern diseases, social transmission and disease understanding].

PMID- 1998169
TI  - Decisions at the end of life: implications following Cruzan.

PMID- 1998171
TI  - [Ambulance helicopters in the mountains].

PMID- 1998172
TI  - [Accidental hypothermia].

PMID- 1998173
TI  - [Mitochondrial diseases--more common than we realize?].
AB  - The last two decades have revealed a novel group of inborn errors with defects on
      the pathways of aerobic energy substrates into the mitochondria or the capacity
      to generate reducing potential from these substrates, as well as those that block
      the oxidative phosphorylation pathway itself. The mitochondrial diseases are
      clinically heterogenous disorders that can affect multiple organ systems, mainly
      the skeletal muscle and nervous system (mitochondrial encephalomyopathies). There
      are a few distinctive syndromes such as Leigh's syndrome, Alper's syndrome,
      Kearns-Sayre's syndrome, myoclonus epilepsy with "ragged-red fibres" (MERRF), and
      MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, strokelike
      episodes). The last year our department has evaluated ten children with
      mitochondrial disorders. Among these are two siblings with Leigh's syndrome and
      cytochrome c-oxidase defect. The first child, a girl, developed the first
      symptoms at the age of four months and died 13 months old. The younger brother
      showed the same clinical picture as his sister. However, the clinical
      neurological picture was stabilized when he was 18 months old, and he is still
      alive at six years of age and slightly psychomotorically retarded.

PMID- 1998175
TI  - [Deep accidental hypothermia with asystole. A successful treatment with heart
      lung machine after prolonged cardiopulmonary resuscitation].
AB  - Extracorporeal circulation can be utilized successfully to rewarm accidental
      hypothermia victims. This paper describes a 51 year-old man who had been immersed
      in cold sea water for about 45 minutes. At the time of rescue his ECG was
      isoelectric. The core temperature was 27 degrees C. Cardiopulmonary resuscitation
      was performed for 190 minutes before extracorporeal circulation was established.
      Without active surface rewarming the temperature had dropped to 24 degrees C.
      Biventricular heart failure became evident during rewarming. Sternotomy and
      pericardiotomy were carried out to exclude cardiac tamponade, which was not
      found. After two hours of reperfusion the patient could be weaned from bypass
      supported by high-dose vasopressor infusion. He was extubated the following day.
      He was discharged after 12 days without any signs of permanent damage to organs.

PMID- 1998174
TI  - [Accidental hypothermia. Risk factors in 29 patients with body temperature of 30
      degrees C and below].
AB  - 29 patients with a body temperature below 30 degrees C (mean 26.4 degrees C) were
      treated during the period 1982-88, both years inclusive. Eight patients were
      severely hypotensive (systolic blood pressure less than 60 mm Hg) and two had
      ventricular fibrillation on admission. Bradycardia (less than 60 beats per
      minute) was noted in ten patients. 12 patients were rewarmed by surface warming,
      17 by extracorporeal circulation with femoral cannulation. 22 patients (76%) were
      discharged alive. Age, sex, body temperature, method and rate of rewarming, serum
      electrolytes, acidosis and the use of blood components did not influence the
      outcome. Renal failure was the only complication associated with a fatal outcome.
      Severe hypotension on admission tended to increase mortality, but logistic
      regression analysis identified the mode of cooling as the only independent risk
      factor for death. A patient cooled indoors had an odd risk of 10.6 of hospital
      mortality compared to one found outdoors. For the sake of convenience, in
      hospitals with the available resources rewarming by extracorporeal circulation
      may be used in patients with circulatory arrest, since this is the easiest way to
      control and support failing circulation. In all other cases carefully monitored
      surface rewarming should be used as this necessitates less use of hospital
      resources and produces equally good results.

PMID- 1998176
TI  - [The effect of conversion from blood donation to plasma donation on serum
      ferritin and hemoglobin].
AB  - In the present study the effect of a change from whole blood to plasma donation
      on iron stores is investigated by measuring serum ferritin levels. Paired serum
      samples from 125 plasma donors showed a significant increase in mean serum
      ferritin level with plasmapheresis. 76% of the plasma donors showed an increase
      in serum ferritin. For plasma donors the haemoglobin concentration is not related
      to serum ferritin level and hence to iron stores, and a change in haemoglobin
      concentration is not related to a change in serum ferritin. Plasma donation is a
      good alternative to whole blood donation for fertile women and for blood donors
      opposed to iron supplements.

PMID- 1998177
TI  - [Results of respiratory treatment in a medical intensive care department].
AB  - During a three-year period 77 patients (43 men and 34 women, aged 21-82 years,
      mean age 62.0 years) were treated with mechanical ventilation in a medical
      intensive care unit. Three patients were treated twice. The most common diagnoses
      (in decreasing order of frequency) were acute exacerbation of chronic obstructive
      pulmonary disease, acute myocardial infarction, cerebrovascular trauma and
      chronic ischemic cardiac disease. The mean duration of ventilation was 6.4 days.
      41 patients (51.3%) survived--80% of whom could be discharged to their home.
      Patients with chronic pulmonary disease showed the highest survival rate, those
      with cerebrovascular disease the lowest, with the cardiac patients in-between. It
      is calculated that it cost NOK 207,000 to treat each patient who survived.

PMID- 1998178
TI  - [Dependence on carisoprodol (Somadril)? A prospective withdrawal study among
      prisoners].
AB  - Carisoprodol (Somadril) was gradually withdrawn for a fortnight in nine male
      prisoners who had been taking daily doses of from 700 to 2,100 mg for at least
      nine months. The patients were assessed clinically during the withdrawal period,
      with special attention to the occurrence of abstinence symptoms. Most of the
      patients reported mental distress, such as anxiety, insomnia and irritability.
      Cranial and muscular pain and vegetative symptoms were also frequently reported.
      Most of these symptoms were transient, and no seizures or psychotic reactions
      occurred. Our information from drug addicts indicates that carisoprodol can be
      misused as a narcotic. The occurrence of abstinence symptoms during withdrawal
      supports this supposition. We propose a more gradual reduction of the doses when
      terminating medication with carisoprodol in general practice.

PMID- 1998180
TI  - [Salivary gland ultrasonography].
AB  - Many pathologic conditions of the salivary gland are diagnosed clinically. Until
      a few years ago, supplementary radiographic methods have only included plain film
      radiography and sialography. Both methods vary in usefulness, and the indications
      are controversial. During the last two decades other imaging methods, both
      radiographic and non-radiographic, have been used, and have provided clinically
      useful information. Probably the most useful of these is ultrasonography. Because
      the salivary glands are superficial structures they lend themselves well to
      ultrasonographic evaluation. Although sialography should still be the method of
      choice for some conditions, ultrasonography alone will often give the correct
      diagnosis. The purpose of this article is to describe the role of sonography for
      imaging pathologic conditions of the salivary glands.

PMID- 1998181
TI  - [Incarcerated obturator hernia].
AB  - Incarcerated obturator hernia is rare. One case is described which demonstrates
      many of the clinical features of the condition. Most affected are elderly women
      with chronic diseases, and the dominating symptoms are the same as for
      obstruction of the small bowel. The Howship-Romberg sign is said to be
      pathognomonic but is present in less than half of the cases. A correct
      preoperative diagnosis is rare. Resection of the small bowel is often necessary.
      The high mortality rate is due to the high age and often poor health of the
      patients, combined with late diagnosis.

PMID- 1998179
TI  - [Surgical pleurodesis in spontaneous pneumothorax].
AB  - Over a five year period 41 operations for spontaneous pneumothorax were performed
      on 38 patients. In all cases a transaxillary thoracotomy was performed in the
      third, or in some cases the fourth, intercostal space. Bullae were resected and
      operative pleurodesis carried out by rubbing the parietal pleura with a dry
      sponge. The indications for operation were: 1) More than one episode of
      pneumothorax on the relevant side. 2) The first incidence of pneumothorax if the
      patient had pneumothorax on the contralateral side before. 3) Continuous leakage
      of air after a week of drainage. One patient had to be reoperated for recurrence
      of pneumothorax, and one was reoperated due to formation of a large postoperative
      haematoma. One patient developed paresis of the serratus anterior muscle due to
      lesion of the long thoracic nerve.

PMID- 1998182
TI  - [Mitochondrial diseases. Diagnostic light and electron microscopic changes in
      muscle biopsies from patients with mitochondrial myopathy].
AB  - Mitochondrial myopathy can be caused by several metabolic defects in the
      mitochondria. Cells with high levels of oxidative metabolism, such as skeletal
      muscle, myocardium and brain cells, are particularly vulnerable to these defects.
      We describe the structural changes in muscle biopsies from 49 patients with
      mitochondrial myopathy. The younger patients were often symptom-free, but the
      possibility of a genetic defect was suggested by the family history. "Ragged-red
      fibres" were found in 10% of the biopsies. Typical paracrystalline inclusions
      were seen in the mitochondria of the oldest patients. Electron-lucent matrix and
      increased thickness of the inner membranes of the mitochondria in particular were
      found in the younger patients. Disorganization of cristae, with cristolysis and
      unfolding of the cristae was also found. We suggest that structural mitochondrial
      changes in mitochondrial myopathy constitute a stepwise process and that the
      mitochondrial alterations of the cristae may represent an early stage in the
      morphogenesis of mitochondrial disease.

PMID- 1998183
TI  - [Wound glueing].

PMID- 1998184
TI  - [Hypothyroidism. Emphasis on clinical aspects or laboratory tests? Report about
      well known facts which, however, can be doubted].
AB  - This article discusses the reliability of laboratory-based diagnosis of
      hypothyroidism by means of combined determination of TSH and FT4. Differential
      diagnoses and supplementary tests are listed, and administrative and analytical
      errors reviewed. It is concluded that unexpected results should not be accepted
      without undertaking control analyses and supplementary examinations. Partial
      selective peripheral resistance to thyroid hormones (persons who have normal TSH
      and FT4 but need thyroxine therapy) is a very uncommon condition. Patients
      suspected of this disorder should be referred to their respective regional
      hospitals, and the results of the study should be published in international
      journals.

PMID- 1998185
TI  - [Urinary tract infections. Views on microbiological diagnosis and resistance
      determination].
AB  - Urinary tract infection is a common problem affecting every fifth woman during
      her life. Although the clinical diagnosis is easy, and is based mainly on
      symptoms and microscopy of urine sediment, the microbiological diagnosis is often
      difficult. Escherichia coli is the main etiologic agent, causing urinary tract
      infection in approximately 80% of the cases. Adherent, uropathogenic E coli
      strains are associated with pyelonephritis and relapse. Staphylococcus
      saprophyticus is a frequent cause of urinary tract infections in fertile women.
      The urethral syndrome, caused by several agents, is an important factor in
      differential diagnosis. Microscopy is the cornerstone of all diagnostics of
      urinary tract infections. A urine culture that is taken, handled, transported and
      interpreted satisfactorily can provide valuable information with respect to
      diagnosis, treatment, prophylaxis and epidemiology.

PMID- 1998186
TI  - [Should ulcer treatment be aimed against Helicobacter pylori?].

PMID- 1998187
TI  - [A psychiatrist crosses his tracks--development of regional psychiatry].

PMID- 1998188
TI  - [Sudden infant death].

PMID- 1998189
TI  - [The lipid hypothesis--who will pay the bill?].

PMID- 1998191
TI  - [Liposuction].

PMID- 1998190
TI  - [Indoor climate and occupational health--experiences from Hedmark and Oppland].

PMID- 1998192
TI  - Teratogenicity study of tri-n-butyltin acetate in rats by oral administration.
AB  - A teratological test was carried out on tri-n-butyltin acetate (TBTA) used as a
      biocide and anti-fouling agent. Pregnant Wistar rats were treated orally with
      TBTA at dose levels of 0, 1, 2, 4, 8, and 16 mg/kg from days 7-17 of gestation.
      Cesarean sections were performed on day 20 of gestation. In pregnant rats,
      salivation and depression of body weight gain and food intake were observed at a
      late stage of pregnancy at the highest dose level of TBTA. Atrophy of the thymus
      was also observed in a dose-dependent manner on day 20 of gestation. In the
      fetuses, treatment with the highest dose level increased embryonic and fetal
      deaths, increased the incidence of fetuses with cleft palate, cervical rib and/or
      rudimentary lumbar rib, and decreased the body weights of fetuses.

PMID- 1998193
TI  - Effects of prolonged low-level cadmium exposure on the tadpole immune system.
AB  - Uninjected (Group I) and sheep erythrocyte (SRBC)-injected (Group II) Rana
      tadpoles were exposed to varying sublethal concentrations of cadmium (Cd) for 6
      weeks. In order to assess possible effects on the tadpole immune system we
      determined pre-B, B mu, and plasma cell (PC mu) frequencies in liver and
      mesonephros of Group I larvae, and hemagglutinating antibody (HA) titers of Group
      II animals. Group I and Group II control animals were cultivated in water with no
      added Cd (0 ppm), while treatments were set at 0.1, 0.2, 0.4 and 0.8 ppm Cd. We
      found that (a) Cd appeared to stimulate a significant increase in the frequency
      of B mu cells in animals treated at 0.4 and 0.8 ppm, (b) certain treated Group II
      larvae contained significantly increased amounts of HA in their serum, while
      their serum protein concentrations were not significantly different, and (c)
      there was a dose-related increase in tissue Cd levels in treated Group II larvae.
      Our observations suggest that chronic low-level exposure to Cd may (a) result in
      a slight increases in the frequency of B mu cells in unimmunized animals, (b)
      increase immune responsiveness of immunized larvae, and (c) increase liver and
      mesonephros accumulations of Cd. Preliminary studies indicated that cytosolic Cd
      is associated with a protein which appears to be similar to mammalian
      metallothionein.

PMID- 1998194
TI  - Platelet-derived growth factor blocks the increase in intracellular free Ca2+
      caused by calcium ionophores and a volatile anesthetic agent in Swiss 3T3
      fibroblasts without altering toxicity.
AB  - Platelet-derived growth factor (PDGF) produced an almost complete block of the
      increase in intracellular free Ca2+ concentration ([Ca2+]i) in Swiss 3T3
      fibroblasts caused by the Ca2(+)-selective ionophores 4-bromo-A23187 and
      ionomycin, and by the volatile anesthetic agent halothane. The effect of PDGF was
      similar to the decreased [Ca2+]i response to Ca2(+)-ionophores produced by
      phorbol 12-myristate 13-acetate, an activator of protein kinase C. There was no
      effect of PDGF or PMA on the acute or delayed toxicity of the Ca2(+)-ionophores
      to Swiss 3T3 cells, suggesting that the increase in [Ca2+]i is not the direct
      cause of toxicity of these agents.

PMID- 1998195
TI  - Mutagenicity of 3-nitrodibenzofuran and 3-aminodibenzofuran.
AB  - Mutagenicities of 3-nitrodibenzofuran and 3-aminodibenzofuran were examined using
      Salmonella typhimurium TA98 and TA100. Strong mutagenicity was found in both
      compounds. The mutagenic potency of 3-nitrodibenzofuran was approximately 3.5
      fold stronger in TA98 and twice stronger in TA100 than that of benzo[a]pyrene.
      Mutagenicity of 3-aminodibenzofuran was observed under metabolic activation and
      was 10 times stronger in TA98 and about 5 times stronger in TA100 than that of
      benzo[a]pyrene.

PMID- 1998196
TI  - Exposure of 1,1,1-trichloroethane and dose-related excretion of metabolites in
      urine of printing workers.
AB  - The quantitative relationship between the time-weighted average exposure by
      inhalation to 1,1,1-trichloroethane and excretion of metabolites in urine at the
      end of a work shift was investigated in 48 male printing workers exposed to the
      solvent at levels below 65 ppm. Male control subjects, 10 in all, were also
      investigated. Statistical analysis showed that there is a linear relationship
      between the two exposure indicators, suggesting that occupational exposure to
      1,1,1-trichloroethane can be bio-monitored by means of urinalysis for either
      total trichloro-compounds or trichloroacetic acid. The correlation coefficient
      was higher for total trichloro-compounds (r = 0.86-0.89 depending on correction
      for urine density) than trichloroacetic acid (r = 0.50-0.71), which suggests that
      the former is a better indicator of exposure to 1,1,1-trichloroethane than the
      latter. The calculations based on the present study suggest that, at the end of
      the shift, only less than 2% of 1,1,1-trichloroethane absorbed will be excreted
      as metabolites in urine.

PMID- 1998197
TI  - Teratogenicity of 3,3-dimethyl-1-phenyltriazene: distribution in rats and rat
      embryos.
AB  - 3,3-Dimethyl-1-phenyltriazene (DMPT) is a methylating agent which is
      carcinogenic, teratogenic and mutagenic which, in the rat, provides a
      reproducible animal model with which to study the basis of chemically-induced
      micrognathism. The basis of teratogenic organotropism of DMPT and other
      methylating teratogens is unknown. The present study was undertaken to determine
      if limited chemical distribution within the embryo was responsible for the
      organotropism of DMPT. Whole-embryo autoradiographs and liquid scintillation
      analysis indicated that although DMPT may have some limitations of chemical
      distribution within the embryo, these limitations are not sufficient to explain
      its teratogenic organotropism.

PMID- 1998198
TI  - Modulation of carbon tetrachloride hepatotoxicity and xenobiotic-metabolizing
      enzymes by corticosterone pretreatment, adrenalectomy and sham surgery.
AB  - These investigations sought to determine the role of physiological concentrations
      of natural glucocorticoids in modulating chemical toxicity, and to ascertain if
      effects on toxicity may be due to alterations of chemical metabolizing enzymes by
      glucocorticoids. The hepatotoxic response to carbon tetrachloride (CCl4) in
      adrenalectomized or naive Long Evans rats treated with corticosterone was
      assessed. Alterations of hepatic cytochrome P-450 concentration, mono-oxygenase
      activities, NADPH-cytochrome (P-450)c reductase activity, and glutathione S
      transferase activity were examined. Adrenalectomy and to a lesser extent sham
      surgery were protective, but corticosterone administration increased CCl4
      hepatotoxicity. Corticosterone administration to adrenalectomized or sham
      operated rats reduced the protective effect of these treatments. Correlating with
      the in vivo response, mono-oxygenase activities decreased after adrenalectomy and
      sham surgery, but increased with glucocorticoid administration. These studies
      suggest that basal, stress-associated, and pharmacological concentrations of a
      natural glucocorticoid can modify chemical toxicity and alter hepatic enzymes
      important to chemical metabolism.

PMID- 1998199
TI  - The effect of glutathione monoethyl ester on the potentiation of the acute
      toxicity of methyl parathion, methyl paraoxon or fenitrothion by diethyl maleate
      in the mouse.
AB  - Depletion of hepatic glutathione in the mouse by pretreatment with diethyl
      maleate (DEM) is known to potentiate the acute toxicities of many dimethyl
      substituted organothiophosphate insecticides. However, certain studies have
      raised doubts regarding the participation of glutathione in the detoxification of
      methyl parathion in the mouse, and hence the putative mechanism of action of DEM
      induced potentiation of this insecticide. The present study evaluates the
      hypothesis that DEM potentiates the acute toxicities of methyl parathion, methyl
      paraoxon, and fenitrothion by a mechanism other than glutathione depletion. One
      hour following pretreatment of mice with DEM (0.75 ml/kg i.p.), glutathione was
      markedly depleted and the acute toxicities of methyl parathion, methyl paraoxon
      and fenitrothion were potentiated. Administration of glutathione monoethyl ester
      (20 mmol/kg p.o.) to DEM-pretreated mice attenuated DEM-depletion of hepatic
      glutathione, or maintained glutathione at or above control levels. However,
      glutathione monoethyl ester did not alter the DEM-induced potentiation of the
      lethality of these insecticides. Furthermore, administration of glutathione
      monoethyl ester to naive mice increased hepatic glutathione levels, but did not
      affect the percentage of animals succumbing to a challenge dose of methyl
      parathion, methyl paraoxon, or fenitrothion. These data indicate that DEM
      potentiates the toxicity of methyl parathion, methyl paraoxon or fenitrothion by
      a mechanism unrelated to hepatic glutathione content.

PMID- 1998201
TI  - Chlorothalonil exposure of workers on mechanical tomato harvesters.
AB  - Worker exposure to chlorothalonil (tetrachloroisophthalonitrile, Bravo during
      mechanical tomato harvester operations of fruit for processing was estimated from
      passive dermal dosimetry monitoring (gauze pad and undershirt dosimetry), air
      concentration measurements and hand washes. Gauze pad dosimeters placed outside
      of workers' clothing gave an average potential dermal exposure of 499.6
      micrograms/h. Dermal exposure based on undershirt dosimetry averaged 43.4
      micrograms/h. Air concentrations ranged from 0.002-0.02 microgram/l. Dislodgeable
      fruit residues were measured and used to develop transfer factors (cm2 h) for
      both the pad dosimetry (450) and shirt dosimetry (40). Study results indicate
      that normal work clothing provides a 90% reduction in dermal exposure to
      chlorothalonil and that contribution of inhalation to total exposure ranges from
      8.1-28%.

PMID- 1998200
TI  - Developmental levels and androgen responsiveness of hepatic mono-oxygenases of
      male rats perinatally exposed to maternally administered cimetidine.
AB  - Cimetidine, a widely prescribed, potent histamine H2-receptor antagonist, is
      unrelatedly a mild antiandrogen. Since perinatal androgens are essential for
      normal masculine imprinting, we wanted to determine if maternally administered
      cimetidine interfered with the development of the male offspring's sex-dependent,
      hepatic drug-metabolizing enzymes. Cimetidine was administered in the mothers'
      drinking water at several levels reflecting both human and rat therapeutic-like
      doses from day 17 of gestation through day 7 of lactation. With the exception of
      a 30% decline in the Vmax for hexobarbital hydroxylase during adulthood, the
      developmental profile of microsomal drug-metabolizing enzymes, when measured at
      1, 4 and 18 weeks of age, was generally unaffected by perinatal exposure to
      cimetidine. Furthermore, the levels of various components of the hepatic mono
      oxygenase system (i.e. heme, cytochromes P-450 and b5, hexobarbital hydroxylase
      and p-chloro-N-methylaniline demethylase) following orchidectomy and androgen
      replacement at physiologic and inductive concentrations, were basically the same
      in control and cimetidine-exposed rats.

PMID- 1998202
TI  - A comparison of cholinergic effects of HI-6 and pralidoxime-2-chloride (2-PAM) in
      soman poisoning.
AB  - The effects of HI-6 and pralidoxime chloride (2-PAM) on soman-induced lethality,
      time to death and several cholinergic parameters in rats were compared to
      understand the beneficial action of HI-6. Treatment with atropine sulfate (ATS)
      or HI-6 alone protected against 1.2 and 2.5 LD50s of soman respectively, whereas
      2-PAM or methylated atropine (AMN) alone afforded no protection. Addition of ATS,
      but not AMN, to HI-6-treated rats enhanced the protection from 2.5 to 5.5 LD50s.
      HI-6 increased the time-to-death, while 2-PAM had no effect; a combination of HI
      6 and ATS provided the most significant increase in time-to-death. Cholinesterase
      (ChE) activity was not altered in any tissue by ATS, HI-6 or 2-PAM treatment
      individually, but was markedly inhibited in all tissues by 100 micrograms/kg of
      soman. In soman-poisoned rats, the HI-6, but not the 2-PAM, group had
      significantly higher levels of ChE in blood and other peripheral tissues than did
      the group given soman alone. Neither HI-6 nor 2-PAM affected soman-inhibited ChE
      in the brain. Additional ATS treatment had no effect on ChE activity. HI-6 and 2
      PAM neither modified baseline brain acetylcholine (ACh) or choline (Ch) levels
      nor protected against soman-induced ACh or Ch elevation. 2-PAM exhibited a 4-fold
      more potent in vitro inhibition of 3H-quinuclidinyl benzilate (3H-QNB) binding
      and sodium-dependent high-affinity Ch uptake (HACU) than did HI-6 in brain
      tissues. The findings that 2-PAM is a more potent in vitro inhibitor of
      muscarinic receptor binding and HACU than HI-6, and yet neither elevates ChE
      activity in the periphery nor protects rats against soman poisoning, indicate the
      importance of higher ChE activity in the periphery of HI-6-treated rats.
      Maintenance by HI-6 of a certain amount of active ChE in the periphery appears to
      be important for survival after soman exposure.

PMID- 1998203
TI  - Correlation of changes in serum analytes and hepatic histopathology in rats
      exposed to carbon tetrachloride.
AB  - Clinical pathology data can significantly contribute to the characterization of a
      disease process if suitable time points for sample collection are chosen and
      combined with the measurement of biochemical analytes that are sensitive and
      specific for damage to a potential target organ. Using a well-defined model for
      hepatotoxicity, we correlated histopathological lesions in the liver with changes
      in selected serum analytes. Groups of Fischer-344 rats were treated with carbon
      tetrachloride (280 mg/kg in corn oil) for 1, 2, 4, 6, 8 or 10 days. Subgroups
      were allowed to recover for 1, 5 or 8 days, at which time blood and liver
      specimens were collected. Histologically, necrosis was detected in livers from
      rats treated for 1 and 2 days and allowed to recover for 1 day. This was followed
      by generalized fatty change in animals treated for longer periods. The maximum
      severity of fatty change occurred 7-12 days (total experimental time). A sharp
      rise and fall (48 h) in cytosolic enzyme activities were seen in serum. This
      preceded gradual increases in all analytes measured which eventually peaked at 9
      11 days (total experimental time). The pattern seen in biochemical analytes
      paralleled the development of marked fatty change. We discuss relationships
      between the histologic and biochemical findings and conclude that appropriate
      clinical biochemistry measurements in a toxicology experiment can provide
      valuable mechanistic information.

PMID- 1998204
TI  - Shifting necrosis: butylated hydroxytoluene (BHT) and phenobarbital move cocaine
      induced hepatic necrosis across the lobule.
AB  - Cocaine (60 mg/kg i.p.) caused centrilobular necrosis in the livers of 55% of
      DBA/2Ha mice. Pretreatment with phenobarbital (PB, 3 x 80 mg/kg i.p.) increased
      the incidence of necrosis to 70% and shifted this damage to the midzonal region.
      Pretreatment with butylated hydroxytoluene (BHT, 0.1% in diet) increased the
      severity of the centrilobular damage and increased the incidence to 90%. Combined
      treatment with both PB and BHT shifted the site of necrosis to the periportal
      region of the liver, and induced necrosis in all animals. Microsomal
      malondialdehyde (MDA) did not reflect the extent of the damage and/or correlate
      with the site of damage. These results argue against a causal role for lipid
      peroxidation in the mechanism of cocaine hepatotoxicity, and demonstrate that
      prior exposure to enzyme-inducing agents can increase sensitivity and
      dramatically alter the site of cell damage.

PMID- 1998205
TI  - Effect of dibutyltin dilaurate on regional brain polyamines in rats.
AB  - Administration of dibutyltin dilaurate (DBTL; 0, 20 or 40 mg/kg body wt.) by
      gavage to rats for 3 consecutive days produced a significant increase in
      polyamine levels in selected brain areas. At the higher dose of DBTL (40 mg/kg)
      spermidine levels were raised in pons-medulla, hypothalamus and frontal cortex
      while spermine levels increased in pons-medulla, hippocampus and frontal cortex
      regions. At the lower dose (20 mg/kg) only a slight increase in polyamine levels
      occurred. The observed induction in regional brain polyamines in DBTL-treated
      rats may lead to disturbances in synaptic function and further enhance its
      neurotoxic potential.

PMID- 1998206
TI  - In vitro penetration of tritium-labelled water (THO) and [3H]PbTx-3 (a red tide
      toxin) through monkey buccal mucosa and skin.
AB  - The permeability coefficients (Kp) for tritium-labelled water (THO) were
      determined in human and monkey skin, and monkey buccal mucosa. Kp of human skin
      (0.47 x 10(-3) cm/h) correlated favorably with previous reports. Kp of hydrated
      monkey skin for THO (0.77 x 10(-3) cm/h) was not significantly different (P
      greater than 0.05) from Kp of hydrated human skin (0.88 x 10(-3) cm/h). Kp of
      monkey buccal mucosa for THO (6.15 x 10(-3) cm/h) was significantly greater than
      that for monkey skin. Penetration and disposition of [3H]PbTx-3 into layers of
      monkey buccal mucosa and skin was determined. [3H]PbTx-3 (5-7 microCi) dissolved
      in 2 ml of water was applied to epithelial/epidermal surface (2.8 cm2) at zero
      time. The relative percent dose recovered from the upper layers of buccal mucosa
      (epithelium) and skin (epidermis) varied, but at each time interval was less than
      2.5% of the dose. At most of the time intervals (2-24 h), a larger percent of the
      dose was recovered from the inner layer of the buccal mucosa (lamina propria)
      than from the inner layer of skin (dermis). After 24 h, as much as 34 or 13% of
      the dose was recovered from lamina propria or dermis, respectively. At each time
      interval studied, less than 2% of dose of [3H]PbTx-3 penetrated into the receptor
      fluid which bathed the inner surfaces of the lamina propria or dermis. The
      results of this study demonstrate that monkey buccal mucosa is more permeable
      than skin to THO and PbTx-3.

PMID- 1998207
TI  - Relationship of clastogenic effects of zirconium oxychloride to dose and duration
      of exposure in bone marrow cells of mice in vivo.
AB  - Zirconium oxychloride was administered as a single oral dose to laboratory-bred
      Swiss albino mice corresponding to 1/2, 1/6 and 1/20 of the LD50 values. Bone
      marrow cells were screened after 6, 12 and 24h for chromosomal aberrations
      following an air-drying-Giemsa schedule. The frequencies of chromosomal breaks
      and alterations induced increased significantly at a rate directly proportional
      to the concentration used. The increase was also related to the period after
      exposure, although to a less extent than the concentration used. No direct
      relationship could be observed to the sex of the animal.

PMID- 1998208
TI  - The murine local lymph node assay: results of an inter-laboratory trial.
AB  - The local lymph node assay is a novel predictive test for the identification of
      contact allergens. The collaborative study reported here was performed to
      evaluate the reliability of the method when performed in independent
      laboratories. Eight chemicals were examined in each of 4 participating
      laboratories and results compared with predictions of skin-sensitizing activity
      made from concurrent Magnusson and Kligman guinea-pig maximization tests
      performed in a single laboratory. The local lymph node assay has as its
      theoretical basis the fact that contact allergens induce T-lymphocyte
      proliferative responses. In practice, predictions of contact-sensitizing
      potential are made following measurement of proliferation in lymph nodes draining
      the site of exposure to chemical, and derivation of a stimulation index using
      control values as the comparator. Although in the present study there was some
      variation between laboratories with respect to the absolute stimulation indices
      recorded, it was found that with all chemicals each laboratory made the same
      predictions of sensitizing activity. Six chemicals (2,4-dinitrochlorobenzene,
      formalin, eugenol, isoeugenol, p-phenylenediamine and potassium dichromate)
      yielded positive responses, and two (methyl salicylate and benzocaine) were
      negative, in each laboratory. Furthermore, with 7 of the 8 chemicals tested there
      was no significant difference between laboratories in terms of the
      characteristics of the dose-response relationships recorded. With the exception
      of one chemical (benzocaine), predictions made with the local lymph node assay
      were in accord with those derived from guinea-pig maximization tests. These inter
      laboratory comparisons demonstrate that the local lymph node assay is a robust
      and reliable method for the identification of at least moderate and strong
      contact allergens.

PMID- 1998209
TI  - Effects of sulfhydryl modulation on ethyl acrylate-induced forestomach toxicity.
AB  - Acute administration of a single dose of ethyl acrylate (EA) to F344 rats by
      gavage caused time- and dose-dependent forestomach edema. Evidence from our
      laboratory and others suggested that EA is hydrolyzed to acrylic acid (AA) and
      ethanol both in vivo and in vitro. The major metabolites detected in teh urine of
      rats treated with EA were derivatives of the glutathione conjugates of EA and AA.
      The current work was undertaken to investigate the effects of sulfhydryl
      depleting agents (diethylmaleate and fasting) and sulfhydryl-containing agents
      (cysteine and cysteamine) on EA-induced forestomach edema. Results presented in
      this report revealed that pretreatment of rats with sulfhydryl-containing
      chemicals such as cysteine or cysteamine has potentiated EA-induced forestomach
      edema. In contrast, depletion of indigenous sulfhydryls by fasting of rats or
      pretreatment with diethylmaleate (DEM) protected against EA-induced forestomach
      edema. Furthermore, repetitive daily administration of EA by gavage induced
      mucosal forestomach hyperplasia. Co-administration of cysteamine and EA resulted
      in a significant enhancement of the severity of EA-induced forestomach mucosal
      hyperplasia. In conclusion, current data suggest that modulation of indigenous
      sulfhydryls play a role in EA-induced forestomach toxicity; however, the exact
      mechanism underlying this role remains to be characterized.

PMID- 1998210
TI  - Acetanilide 4-hydroxylase and acetanilide 2-hydroxylase activity in hepatic
      microsomes from induced mice.
AB  - A simple and sensitive method for the separation of 14C-labelled acetanilide, 4
      hydroxyacetanilide, 3-hydroxyacetanilide and 2-hydroxyacetanilide was developed
      using thin-layer chromatography. This separation is the basis for the assay of
      acetanilide 4-hydroxylase and acetanilide 2-hydroxylase activity in liver
      microsomes from DBA2/N male mice that had been treated with phenobarbital, 3
      methylcholanthrene, isosafrole or n-butylbenzodioxole. Microsomes were incubated
      with [14C]acetanilide and extracted with benzene and ethyl acetate. The extract
      was applied to silica gel plates and developed with a hexane/isopropanol/ammonium
      hydroxide/water solvent system. The radiolabelled phenolic metabolites and the
      parent compound were detected using a Berthold Automatic TLC Linear Analyzer.
      Although the 4-hydroxylated metabolite was the primary product detected, this
      method can be used to detect other phenolic metabolites.

PMID- 1998211
TI  - Primary health care: delivery or participation.

PMID- 1998212
TI  - Managing common oral problems: some considerations.
AB  - In the absence of early interventions, incipient dental problems can progress to
      destructive and even fatal outcomes. It is particularly important that primary
      health personnel correctly diagnose a presenting condition and provide care as
      early as possible. Some considerations are presented to assist in recognizing and
      managing common mouth problems.

PMID- 1998213
TI  - Incidence of duodenal ulcer in the northern Savannah of Nigeria.
AB  - In 4 years, 200 patients were admitted to the University of Maiduguri Teaching
      Hospital, in the Northern Savannah of Nigeria, with a clinical diagnosis of
      peptic ulcer; 60 had the diagnosis of duodenal ulcer confirmed on barium meal or
      at operation, giving an incidence of 6/1000 adult admissions (excluding
      obstetrics). There were no gastric ulcers. Forty-four patients had a 'simple
      ulcer', 10 presented with gastric outlet obstruction, five with peritonitis
      following perforation and one with haematemesis. There were 44 males, and 16
      females, with a mean age of 34 years and mean length of history of 44 months.
      Contrary to previous published reports improved diagnostic facilities have shown
      duodenal ulcer to be relatively common in the Northern Savannah of West Africa.

PMID- 1998214
TI  - Determinants of severity of neonatal hyperbilirubinaemia in ABO incompatibility
      in Nigeria.
AB  - The study was designed to determine factors responsible for the severe neonatal
      hyperbilirubinaemia sometimes found in ABO incompatibility in Nigeria. In 50
      jaundiced babies who were ABO-incompatible it was found that the mean serum
      bilirubin level was significantly higher in outpatients than inpatients; this
      difference was probably due to the delay in recognizing jaundice among the
      outpatients and, possibly also to the slightly higher number of G-6-PD deficient
      babies in the same group, and their greater exposure to icterogenic agents. The
      results of serological studies suggest that ABO-incompatibility was responsible
      for neonatal jaundice in only 36% of these babies. Among the inpatients the need
      for exchange blood transfusion was more common in babies of mothers with immune
      anti-A or anti-B titres of 1:64 or more (P less than 0.001). Neonates at risk of
      ABO-haemolytic disease can be identified at birth by direct positive Coombs test
      and detection of immune anti-A or anti-B antibodies in the mother's serum.

PMID- 1998215
TI  - Sustainable health.

PMID- 1998217
TI  - Konzo, a paralytic disease observed in southern Tanzania.

PMID- 1998216
TI  - Role of traditional health workers in prevention and control of AIDS in Africa.

PMID- 1998218
TI  - A comparative study of pyuria and asymptomatic bacteriuria in school children.
AB  - Urine samples were collected from 1,000 school children aged between 4 and 15
      years. Twenty-eight children had significant bacteriuria, while 32 had
      significant pyuria. Seventeen pupils had both significant bacteriuria and pyuria.
      The study shows that although there is a positive association between pyuria and
      bacteriuria, the absence of pus cells in urine samples cannot be taken as
      evidence of absence of bacteriuria, nor can the presence of pyuria alone be
      considered as an indication of infection. Escherichia coli is the commonest agent
      in school children with significant bacteriuria.

PMID- 1998219
TI  - Occupational HIV infection and health care workers in the tropics.
AB  - A literature review revealed 33 reports of health care workers who have
      contracted HIV infection as a result of their work. Four of these were expatriate
      doctors who had worked in Africa. The commonest mode of transmission was
      needlestick injury, but several infections acquired through contact or skin or
      mucous membrane with infected blood have been reported. In this paper we outline
      how the risk of HIV infection in a health care worker can be estimated for a
      given number of exposures. The formula is based on the known likelihood of
      transmission per needlestick, the seroprevalence rate among patients, and the
      number of needlestick injuries that occur. We also suggest a list of measures by
      which the risk of HIV transmission to hospital staff can be minimized.

PMID- 1998220
TI  - Community involvement in health: why is it necessary?

PMID- 1998221
TI  - Integration of mother and child health services in Ethiopia.
AB  - In Wollo region of Ethiopia, various non-governmental officers have been working
      closely with each other and with the Regional Health Department to implement the
      policy of daily integrated mother and child health services. The record cards,
      registers, procedures and training courses of the separate 'vertically' organized
      services were brought together to enable the development of a model integrated
      service. There were improvements in accessibility, acceptability and output of
      the services. The system was evaluated by a joint Ministry of Health and UNICEF
      team, and was adopted for use in the rest of Ethiopia.

PMID- 1998222
TI  - Breast-feeding practices of women in rural Orissa, India.

PMID- 1998223
TI  - Rational prescribing.

PMID- 1998224
TI  - Placental malaria and fetal growth failure.

PMID- 1998225
TI  - A paediatric tuberculosis programme.

PMID- 1998226
TI  - A comparison of wound complications after inguinal hernia repair under local and
      general anaesthesia.
AB  - Ninety-one male patients with unilateral reducible inguinal hernia were randomly
      allocated to receive either general or local anaesthesia in order to compare the
      incidence of postoperative wound complications following both methods of
      anaesthesia. Forty-seven patients received local anaesthesia while 44 received
      general anaesthesia. Two patients (4.3%) who received local anaesthesia and three
      patients (6.8%) who received general anaesthesia developed various types of
      postoperative wound complications. Chi-squared test however showed no significant
      difference in the incidence of wound complications between the two groups of
      patients.

PMID- 1998227
TI  - Cytological findings in the sputum of cigarette-smoking Cameroonians and non
      smokers.

PMID- 1998228
TI  - Management of intraperitoneal rupture of amoebic liver abscess: a 6-year
      experience with 11 cases in Port Harcourt, Nigeria.

PMID- 1998229
TI  - Fulminant amoebic colitis in pregnancy.

PMID- 1998230
TI  - Nurse education: in need of radical change for PHC?

PMID- 1998231
TI  - Pneumonia in adults: a guide to diagnosis and management in the district
      hospital.

PMID- 1998232
TI  - [Drug prescriptions in general practice].

PMID- 1998233
TI  - [Treatment of cervix cancer in Denmark].
AB  - The current status of cervical cancer treatment in Denmark is discussed.
      Diagnostic aspects and problems of classification are presented briefly
      supplemented with a comment on new prognostic parameters based on a
      semiquantitative score system and flow cytometry. Surgery is the treatment of
      election for the early stages whereas radiotherapy is the treatment of choice in
      advanced stages. Chemotherapy should only be employed in the framework of
      clinical trials. It is concluded that centralised treatment should be maintained.

PMID- 1998234
TI  - [Humero-scapular periarthrosis].
AB  - Humero-scapular periarthrosis (PH) is defined as an idiopathic painful condition
      in the shoulder with simultaneous limitation of active and passive movements in
      all directions. The condition is characterized by three phases: a painful period,
      a period dominated by stiffness and a period of recovery. PH is commonest between
      the ages of 40 and 60 years and the cumulated risk is estimated to be 2%. The
      incidence is higher in diabetics. The cause of PH is unknown and knowledge of the
      pathogenesis is very limited. Histological examination shows inflammation and
      fibrosis. Association with other pathological conditions of the upper limb or
      medical conditions, except diabetes mellitus, has not been documented with
      certainty. The average duration is 30 months but recovery without functional
      defects is common. Treatment is symptomatic and consists primarily of analgesics
      and rest during the painful phase. Local injections of steroids may be of effect.
      Exercises may be employed once the pain is under control and these have the
      object of improving mobility and increasing muscular strength.

PMID- 1998235
TI  - [Leukotrienes. A review of the significance for disease in man and the
      possibilities for therapeutic intervention].
AB  - The leukotrienes constitute a group of 5-lipoxygenase catalyzed metabolites of
      arachidonic acid, the cellular effects of which may be divided into two broad
      categories. Leukotriene B4 is predominantly a leukocyte stimulant, and has
      recently been observed to represent the inflammatory cell component of a mutual
      activation mechanism between inflammatory cells and the immune system. It is thus
      anticipated that LTB4 acts as an inflammatory mediator and immune regulator in a
      variety of immune-mediated disorders. The presence of LTB4 in inflamed tissues
      from patients with psoriasis, rheumatoid arthritis and chronic inflammatory bowel
      disease renders it probable that the novel class of 5-lipoxygenase inhibitors and
      LTB4 antagonists will be capable of influencing the clinical course of these
      diseases. The other main group is comprised of leukotrienes C4, D4 and E4,
      collectively known as slow reacting substance of anaphylaxis leukotrienes, and
      has been identified primarily in immediate hypersensitivity conditions, e.g.
      bronchial asthma in which the smooth muscle contractile and permeability
      increasing properties of SRS-A appears to contribute to the early
      bronchoconstrictor phase. Leukotriene D4, however, may also be involved in the
      late reaction mediated by inflammatory cells, since it has the ability to
      immobilize neutrophils attracted by LTB4 to the inflammatory focus. The ultimate
      elucidation of the importance of leukotrienes in different diseases awaits the
      outcome of clinical trials with the newly developed highly potent and specific 5
      lipoxygenase inhibitors and leukotriene antagonists.

PMID- 1998236
TI  - [Treatment of infectious diseases with antibacterial drugs in general practice].
AB  - A survey of systemic treatment with antimicrobial drugs in general medical
      practice at Holstebro, Jutland, in March 1987 is presented. The two pharmacies of
      the town recorded all prescriptions to individual patients. The diagnoses were
      recorded by questionnaire, which was returned by all involved physicians. A total
      of 969 persons, equivalent to 2.4 per cent of the population and 5.7 per cent of
      all Health Service contributions, were treated: 39% for upper and 18% for lower
      respiratory infection, 18% for urogenital infection and 7% for skin infection. 6%
      were recorded under "miscellaneous". In 12% of the cases no diagnosis was stated.
      48% were treated with V-penicillin, 20% with ampicillin, 17% with erythromycin
      and 3% with tetracycline. The investigation shows a tendency towards less than
      optimal strategies as regards infections of the respiratory passages and the
      urinary system. Too often a "wide-spectrum therapy" was chosen. This choice meant
      a prolonged term of treatment and larger day-and-night doses leading to
      unnecessary expense. Short-term treatment of uncomplicated infection of the
      urinary system and otitis media were not recorded.

PMID- 1998237
TI  - [Induction of labor when a large fetus is suspected].
AB  - The courses of 945 deliveries in which the infant weighed greater than or equal
      to 3,800 g are reviewed retrospectively with comparison between the deliveries
      which began spontaneously and the induced deliveries. In the deliveries which
      were induced on account of a suspected large foetus, the frequency of emergency
      Cesarean section was tripled and the frequency of vacuum extraction was doubled.
      Significantly more infants had Apgar scores of less than 7 after one minute than
      in the deliveries which began spontaneously. It is concluded that induction of
      labour is not indicated in cases where a large foetus is suspected.

PMID- 1998238
TI  - [Acute poisoning in childhood. 607 admissions during a 5-year period to a Danish
      pediatric department].
AB  - This article presents a review and an analysis of the 607 patients admitted to
      the Paediatric Department in Gentofte University Hospital, Copenhagen, on account
      of all kinds of poisoning during the period of five years from 1980 to 1985. We
      observed that the number of inpatients on account of poisoning constituted 4.5%
      of the total number of inpatients. The female to male ratio was registered as
      0.84. No significant differences in admission of patients in each of the five
      years were found. 97.5% of the children were hospitalized only for two days or
      even less. Of the total number of patients, 75% were observed in the age groups
      up to four years and 53% in the interval between one and three years. Concerning
      the type of poisoning agents: we found that 29% were poisoned with solid
      substances, 24% with chemical-technical agents, 23% with botanical agents, 22%
      with various kinds of medicine and finally 2% with gaseous agents. A possible
      coherence between the different categories of poisoning agents and the age
      intervals was reviewed. 31% of the admitted children developed symptoms, of which
      the most frequently observed were gastrointestinal, cerebral and respiratory. The
      poison categories with the highest frequency of complications were the chemical
      technical agents and those determined by ingestion of medicine.

PMID- 1998239
TI  - [Measurement of the middle ear pressure in preventive examinations of children].
AB  - Tympanometry was performed in 247 children at the prophylactic examinations. The
      children were aged from 15 months to five years and were included consecutively
      and examined only once. In 9% it did not prove possible to perform satisfactory
      tympanograms. 37% had initially pathological tympanometric findings. The
      frequency of pathological tympanometric findings was found to decrease with
      increasing age. Pathological tympanometric findings were found to be
      significantly more frequent in boys. Twenty-two children (8% of the material)
      were tubulated. It is considered that tympanometry is a useful method for
      employment in general practice but that further investigations from general
      practice are still required.

PMID- 1998240
TI  - [Is the clinical diagnosis of acute appendicitis good enough?].
AB  - In order to estimate the specificity of the clinical diagnosis of acute
      appendicitis, case records of 148 patients, who underwent appendectomy or who
      were diagnosed as having periappendicular abscess during one year at a regional
      hospital in Denmark were analyzed. Operations without finding acute appendicitis
      occurred in 25.4 per cent of the patients. The group of women in the fertile age
      (12-50 years) was prone to unnecessary surgery (51.9 per cent in this group had a
      normal appendix). In children, men and non-fertile women only a few patients had
      unnecessary surgery. Belated diagnoses (perforation and/or abscess) were found
      truly in 10.7 per cent of the cases, and, with a significant higher incidence, in
      elderly patients (age greater than 50 years). The possibilities of diminishing
      the incidence of unnecessary surgery and belated diagnoses are discussed.

PMID- 1998241
TI  - [Infection as the precipitating factor in Schonlein-Henoch purpura].
AB  - Shonlein-Henoch's purpura (SHP) is a form of generalized vasculitis. SHP is
      characterized by a haemorrhagic eruption, colicky abdominal pain, renal
      involvement with haematuria and proteinuria, arthralgia and cerebral symptoms in
      the form of headache and seizures. Retrospective investigations have revealed
      that infection with microorganisms may precipitate SHP. The authors were able to
      support this observation by means of a prospective investigation. 2/3 of the 26
      children in the investigation had symptoms of infection one to two weeks prior to
      the onset of symptoms of SHP. Ten children had definite positive signs of prior
      infection. The course of the sedimentation rate and leukocyte counts also support
      the assumption of previous infection.

PMID- 1998242
TI  - [Neonatal sepsis at Rigshospitalet in 1984-1988].
AB  - Eighty-one episodes of bacteremia and candidemia were recorded in 78 infants in
      our neonatal intensive care unit during the years 1984 to 1988. The species
      isolated from monomicrobial episodes were as follows: Enterobacteriaceae 38%,
      group B streptococci or pneumococci 12%, staphylococci 20%, Candida albicans 9%,
      and other species 15%. Polymicrobial bacteremia occurred in 6%. Group B
      streptococci and pneumococci were predominantly isolated from early infections,
      whereas Enterobacteriaceae, Staphylococcus epidermidis and C. albicans were
      associated mainly with late septicemia. More than 80% of the episodes occurred in
      premature infants. During the study period, initial empiric antibiotic therapy
      consisted of ampicillin plus gentamicin. In spite of the fact that
      Enterobacteriaceae isolates, often ampicillin resistant, and penicillinase
      producing staphylococci, were the dominant etiologic agents, choice of this
      initial therapy did not seem to contribute to mortality. Mortality was most
      convincingly associated with overwhelming infections caused by group B
      streptococci and pneumococci.

PMID- 1998243
TI  - [Herpes zoster induced reversible neurogenic bladder dysfunction. Urodynamic
      documentation of reversible bladder paralysis].
AB  - A case of sacral herpes zoster with reversible neurogenic bladder dysfunction
      causing urinary retention is presented. Gradual reversibility of the motoric
      paralysis of the detrusor was demonstrated in cystometrograms. It is stressed
      that treatment should be primarily conservative and that repeated urodynamic
      examinations is essential.

PMID- 1998244
TI  - [Pneumothorax during jet ventilation in laryngobronchoscopy].
AB  - A case of unilateral pneumothorax which occurred during anaesthesia for
      laryngobronchoscopy is presented. The possible causes are discussed. Pneumothorax
      should always be suspected in cases of complicated anaesthesia where jet
      ventilation is employed.

PMID- 1998245
TI  - [Percutaneous cholecystostomy and laser lithotripsy].
AB  - A case of acute cholecystitis in a high risk patient was treated in the acute
      phase with cholecystostomy guided by ultrasound and with introduction of a pig
      tail catheter for drainage. Later, percutaneous laser lithotripsy was undertaken
      via a flexible choledochoscope. The recent percutaneous therapeutic principles
      and the possibilities in biliary calculous disease are reviewed.

PMID- 1998246
TI  - Estimation of frequency-dependent attenuation based on parametric spectral
      analysis and correlation lags of the demodulated echo signal.
AB  - Two new methods for estimating frequency-dependent attenuation are proposed which
      improve the compromise between the estimation variance of this parameter and the
      analyzed tissue volume: 1) parametric spectral estimation of the demodulated
      signal, based on fast Kalman filtering (ARC), 2) implementation of a new mean
      frequency estimator derived from all the available autocorrelation lags (ACn) of
      the demodulated signal. Both methods are applied to simulated echo signals. The
      results are compared to those of other already existing estimators. Both ARC and
      ACn methods provide equivalent results and a better estimation of attenuation
      (accuracy ranging from 1.3 to 8%) than the previous methods do (accuracy ranging
      from 4 to 66%), for analysis windows ranging from 1.5 to 20 microseconds.

PMID- 1998247
TI  - Ultrasonic differentiation of intraocular melanomas: parameters and estimation
      methods.
AB  - In this study, the estimation of ultrasound parameters is evaluated for in vivo
      differentiation of intraocular melanomas. For this purpose, both tissue and image
      parameters of the ultrasound signal are considered. These parameters comprised,
      respectively, the frequency dependent attenuation and backscattering coefficient
      of the melanoma tissue, and the first and second-order statistics of the
      amplitude-modulated and phase-derivative images of the melanomas. A diffraction
      correction procedure has been applied prior to the estimation of the parameters
      to correct the ultrasound signals for the echographic equipment used and for the
      various distances of the region-of-interest to the transducer. In addition, a pre
      processing to select a homogeneous region from the tumours was implemented to
      obtain consistent estimates of the ultrasound parameters, because the accuracy
      and the precision of the parameters would be greatly reduced by the inhomogeneity
      of the melanoma tissue. The estimation methods are evaluated by means of the
      accuracy and precision of the parameters estimated from simulated ultrasound data
      and data obtained from a tissue-mimicking phantom. The mutual correlations of the
      parameters are discussed for the ultrasound data obtained from the melanomas.
      This study enabled a preselection of the independent ultrasound parameters that
      could be used in a discriminant analysis to perform a differentiation of
      intraocular melanomas. The sensitivity and specificity of differentiating spindle
      cell type from mixed-epitheloid meleanomas were 92 and 89 percent, respectively.

PMID- 1998248
TI  - Experimental results in ultrasonic tomography using a filtered backpropagation
      algorithm.
AB  - This paper describes an experimental study in diffraction tomography whose main
      goal was to determine experimentally the performance of the filtered
      backpropagation algorithm in ultrasound tomography. We have built a simple water
      tank with a plane wave source and a scanning hydrophone. The test objects have
      been cylindrical and of a relatively simple structure and made of acrylic and
      silicone rubber. The resulting reconstructions show that the structure and
      position of the objects are well reproduced. The velocity of the objects can also
      be well reproduced if the velocity contrast is not too large. In medical imaging,
      it is most important to see the structure, and since the velocity change in
      biological tissue is small, the method should be well suited for medical imaging.

PMID- 1998249
TI  - In vivo measurements of ultrasonic beam distortion in the breast.
AB  - The phase aberrations encountered by ultrasonic pulses propagating through breast
      tissue in twenty-two female volunteers were measured. The experiments were
      designed to assess the impact of these aberrations on clinical ultrasonic image
      quality for a variety of transducer and imaging geometries. The phase aberration
      profiles of a given patient were correlated with the amount of parenchymal tissue
      determined from that patient's mammogram. These data are useful in assessing the
      image quality achievable with conventional ultrasonic imaging systems, and the
      potential application of adaptive ultrasonic imaging systems. The results
      indicate that phase aberrations significantly degrade breast image quality for
      typical transducer frequencies and sizes.

PMID- 1998250
TI  - A method for in vitro mapping of ultrasonic speed and density in breast tissue.
AB  - A method has been developed for mapping density and ultrasonic speed in 1 mm
      thick slices of soft tissue with a resolution of about 1 mm. Tests using phantom
      sections have verified the accuracy and resolution of the ultrasonic speed maps.
      The method has been applied to breast tissues of three patients including tumors
      and surrounding tissue. Fixing a specimen in 5% formaldehyde did not change the
      degree of local variation in ultrasonic speeds, and raised mean speeds by less
      than 0.8%. The densities with fixing remained almost unchanged at low tissue
      densities (0.93 g/cm3), but rose 1.5% for higher tissue density (greater than
      1.00 g/cm3).

PMID- 1998251
TI  - Effects of writing/speaking on comprehension of information for informed consent.

PMID- 1998252
TI  - Desire for control and choice of antiemetic treatment for cancer chemotherapy.

PMID- 1998253
TI  - Nurses' and lay African Americans' views about behavior.

PMID- 1998254
TI  - The allocation of health care resources.

PMID- 1998255
TI  - Sample sizes and power computation for clinical intervention trials.
AB  - The purpose of this article was to describe basic concepts of sample size and
      power estimation for planning nursing intervention trials and interpreting their
      results. Simple mathematical calculations, using the formulas presented here, can
      be used to estimate the number of subjects required to conduct a study with a
      designated effect size and level of power. These methods are of great importance,
      since most funding agencies require sample size and power estimations before a
      grant is awarded. In general, studies with power lower than .7 or .8 need careful
      consideration before they are implemented. In these situations, it may be wise to
      consider various alternatives for obtaining study subjects or deleting treatment
      groups for investigations involving more than two groups. The formulas presented
      here can also be useful in estimating the power of published research findings.
      Through a quick calculation, the consumer of nursing research can critically
      evaluate the meaning of a negative trial and draw appropriate conclusions for
      future research and practice.

PMID- 1998256
TI  - Resocialization group treatment with the confused institutionalized elderly.

PMID- 1998257
TI  - Understanding adherence to breast self-examination in older women.

PMID- 1998258
TI  - Issues in the measurement of children's locus of control.

PMID- 1998259
TI  - Testing Rogers's theory of accelerating change. The relationships among
      creativity, actualization, and empathy in persons 18 to 92 years of age.

PMID- 1998260
TI  - Patientology one more time.

PMID- 1998262
TI  - Applause for PartnerCare.

PMID- 1998261
TI  - A definition and description of nurse abuse.

PMID- 1998263
TI  - Percutaneous balloon pulmonary valvuloplasty in children.
AB  - This report describes the results and follow-up of 27 patients undergoing
      pulmonary balloon valvuloplasty at Children's Hospital of Wisconsin where this
      procedure has been performed since 1985. The valvuloplasty data at
      catheterization as well as follow-up echocardiograms when available were
      retrospectively reviewed. For 26 patients, the transvalvar gradient changed from
      a mean of 72 mm Hg + 5.2 (SEM) to 29 mm Hg + 4.4 (SEM) (p 0.00001) a mean
      gradient reduction of 58%. No major complications were reported and no patient
      went on to surgical valvotomy. Follow up echocardiograms were available for 26
      patients. Average estimated transvalvar pressure gradients by continuous wave
      Doppler echocardiography were 28 mm Hg at one day (13 patients), 20 mm Hg at mean
      1.5 months (18 patients), 23 mm Hg at mean 8.8 months (12 patients), and 19 mm Hg
      at mean 26 months (8 patients). Percutaneous balloon valvuloplasty gives good
      results in nearly all patients with pulmonary valve stenosis.

PMID- 1998264
TI  - The smoking cessation process.
AB  - The purpose of this study was to identify and describe the smoking cessation
      process as perceived by smokers and ex-smokers. In-depth, open-ended interviews
      were conducted with 25 ex-smokers who had quit smoking for at least 1 year, but
      not more than 7 years, and 22 smokers who had quit smoking for at least 2 weeks
      and returned to smoking. A systematic analysis of content was used to generate
      categories of responses regarding the smoking cessation process. The results of
      this study support and enhance what is known about behavioral change. Although
      further testing for verification is needed, the smoking cessation process as
      described by the study participants is: thinking about quitting, making a case,
      quitting, making adjustments, meeting the challenge, resumption, or maintenance.

PMID- 1998265
TI  - Mortality and morbidity in Wisconsin hospitals.

PMID- 1998266
TI  - Observations on Wisconsin's public health agenda.

PMID- 1998268
TI  - Hospital mortality.

PMID- 1998267
TI  - Public health. Childhood lead exposure in Wisconsin in 1990.
AB  - It will take the cooperation of many people to address the issue of lead
      poisoning. The recent death has dramatized the problem of high dose exposures.
      But a larger challenge is posed by the fact that most preschool children in
      Wisconsin are not screened for lead and as a result many asymptomatic children
      without signs of pica behavior will experience subtle neurological damage as a
      result of low to moderate elevations of lead in blood. Because many of these
      cases occur in children without recognized pica behavior, doctors need to expand
      screening, especially during well child visits, to identify children with
      elevated blood lead levels. Additionally, the public health community and
      property owners need to evaluate and control sources of lead. Major efforts are
      needed to address the lead hazards which now impair hundreds of Wisconsin
      children each year.

PMID- 1998269
TI  - Physicians v machines.

PMID- 1998270
TI  - Program of plenary sessions and advance abstracts of short communications. 35th
      Symposium of the German Society for Endocrinology. Bonn, February 27- March 2,
      1991.

PMID- 1998271
TI  - 1991 75th Anniversary AARN. Our history--a proud heritage 1965-69.

PMID- 1998272
TI  - Maintenance of breastfeeding by prevention of sore nipples.

PMID- 1998273
TI  - Pain corner. No pain? Are you sure?

PMID- 1998274
TI  - Expanded clinical evaluation of lovastatin (EXCEL) study results. II. Assessment
      of the human lens after 48 weeks of treatment with lovastatin.
AB  - The crystalline lenses of hypercholesterolemic patients were assessed before and
      after 48 weeks of treatment with lovastatin or placebo to determine the effect of
      lovastatin on the human lens. Patients were given a biomicroscopic (slit-lamp)
      examination of the lens, and a previously validated, standardized classification
      system was used to describe the findings. A total of 8,245 patients were randomly
      assigned in equal numbers to treatment with placebo or lovastatin 20 or 40 mg
      once or twice daily in this double-blind, parallel-group study. Statistical
      analyses of the distribution of cortical, nuclear and subcapsular opacities at 48
      weeks, adjusted for age and presence of an opacity at baseline, showed no
      significant differences (p less than 0.01) between the placebo and lovastatin
      treated groups. Visual acuity assessments at week 48 were also not found to have
      significantly different distributions among treatment groups. Moreover, no
      significant differences were found among the groups in the frequencies of greater
      than or equal to 2-line worsening in visual acuity with concurrent progression in
      lenticular opacity, cataract extraction, or any spontaneously reported adverse
      ophthalmologic experience. No evidence was found for an effect of lovastatin on
      the human lens after 48 weeks of treatment.

PMID- 1998275
TI  - Effect of left ventricular aneurysm on risk of sudden and nonsudden cardiac
      death.
AB  - Although left ventricular (LV) aneurysm is associated with increased mortality,
      its independent prognostic significance is controversial. To determine the effect
      of LV aneurysm on risk, 121 patients with healed myocardial infarction (MI), 55
      manifesting akinesia on ventriculography (MI group) and 66 with LV aneurysm
      characterized by diastolic deformity (eccentricity) and systolic dyskinesia (LV
      aneurysm group) were studied. At a mean follow-up of 5.7 years, there were 32
      cardiac deaths (12 MI vs 20 LV aneurysm), including 9 sudden deaths (1 MI vs 8 LV
      aneurysm). Multivariate analysis revealed decreasing ejection fraction to be the
      best predictor of total cardiac death, and revascularization to be protective.
      Nonsudden cardiac death was predicted by ejection fraction, absence of
      revascularization and right coronary artery disease, whereas sudden cardiac death
      was predicted by LV aneurysm and the frequency of ventricular ectopic complexes
      on Holter monitoring. In the MI group, ejection fraction was the only significant
      predictor of total cardiac death and nonsudden cardiac death. In the LV aneurysm
      group, total cardiac death, as well as nonsudden cardiac death, were predicted by
      ejection fraction, ventricular tachycardia and right coronary artery disease,
      whereas ventricular tachycardia predicted sudden cardiac death. It is concluded
      that the risk profile for total cardiac death differs between LV aneurysm and MI
      patients, and that LV aneurysm constitutes an independent predictor of late
      sudden cardiac death after MI. Moreover, on a substrate of LV aneurysm, the risk
      factors for sudden cardiac death and nonsudden cardiac death differ, with
      ventricular tachycardia being the sole predictor of sudden cardiac death.
      Furthermore, Holter monitoring is valuable in identifying patients at persistent
      risk of sudden cardiac death.

PMID- 1998276
TI  - Angiographic morphology in unstable angina and its relation to transient
      myocardial ischemia and hospital outcome.
AB  - Complex stenosis morphology frequently occurs in patients with unstable angina
      pectoris. However, its relation to transient myocardial ischemia and hospital
      outcome has not been ascertained. To address this issue, 88 patients with
      significant (greater than or equal to 50%) coronary artery disease presenting
      with angina--new onset (n = 38), worsening (n = 20) or at rest (n = 30)-were
      studied. Patients with left main artery disease, normal coronary arteries or
      occlusion of the ischemia-related arteries were not included in the study.
      Continuous electrocardiographic recordings were obtained during the first 24
      hours. Angiography was performed within 1 week from admission. Complex morphology
      was defined as any stenosis with irregular borders, overhanging edges or
      intracoronary thrombus. Only data referring to the in-hospital outcome were
      considered in this study. Adverse end points were sudden death, myocardial
      infarction and emergency revascularization. Analysis of the angiograms revealed a
      complex morphology in 58 patients (group 1). The remaining 30 patients served as
      control subjects (group 2). Thirty-two of the 58 group 1 patients had an
      unfavorable clinical outcome (positive predictive value, 55%). A similar outcome
      occurred in only 2 of the 30 group 2 patients (negative predictive value, 93%).
      Of the 32 group 1 patients who had an unfavorable clinical outcome, 29 had a
      cumulative duration of transient myocardial ischemia of greater than or equal to
      60 minutes per 24 hours. A similar duration of ischemia, however, was observed in
      another 6 group 1 and in 8 group 2 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1998277
TI  - Anginal symptoms without ischemic electrocardiographic changes during ambulatory
      monitoring in men with coronary artery disease.
AB  - Episodes of angina pectoris without electrocardiographic (ECG) signs of
      myocardial ischemia during 24-hour ambulatory monitoring were studied in 128
      patients with a history of stable angina, angiographically proven coronary artery
      disease and positive exercise test results. In all, 341 episodes of ischemic ECG
      changes (ST-segment depression greater than 1 mm for greater than 1 minute) and
      190 episodes of angina pectoris were observed: 86 episodes consisted of both ECG
      changes and angina pectoris, 255 episodes consisted only of ECG changes, and 104
      episodes only of angina pectoris. Duration and magnitude of ST-segment deviation
      and heart rate at the onset of ischemia were similar in the 86 symptomatic and
      the 255 asymptomatic episodes with ECG changes. The 104 episodes of angina
      pectoris without ECG changes were detected in 44 patients (34%) (group A); 29 of
      them had only episodes with angina pectoris and 15 patients had both--episodes of
      angina pectoris with and without ECG changes. In 84 patients (66%) (group B)
      angina pectoris without ECG changes was not observed; all episodes were
      accompanied by ischemic ECG changes in these patients. No differences in the
      angiographic extent of coronary artery disease and in exercise test data were
      seen in both groups A and B; however, maximal ST-segment depression during
      exercise testing was significantly greater in group B than in group A patients
      (2.4 +/- 0.8 mm vs 1.9 +/- 0.9 mm; p less than 0.05).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1998278
TI  - Dependence of Doppler echocardiographic transmitral early peak velocity on left
      ventricular systolic function in coronary artery disease.
AB  - The influence of systolic function on pulsed Doppler echocardiographic
      transmitral flow velocity patterns was assessed before and after
      postextrasystolic (PES) potentiation in 12 normal subjects (control group) and in
      25 patients with previous healed myocardial infarction (MI) group. Simultaneous
      high-fidelity left ventricular pressure measurements were performed in all
      patients. A programmed single-coupled right ventricular extrasystole was induced
      during echocardiographic and subsequent cineangiocardiographic recordings.
      Adequate angiograms for volumetric analysis in both baseline and PES beats were
      obtained in 23 patients (7 in the control group and 16 in the MI group). PES
      potentiation of contraction was more pronounced in the MI group than in the
      control group. PES changes in ejection fraction, stroke volume and end-systolic
      volume were significantly greater in the MI group than in the control group (11
      vs 5%, p less than 0.005; 15 vs 5 ml/m2, p less than 0.005; and -13 vs -4 ml/m2,
      p less than 0.01, respectively). In contrast, PES potentiation prolonged the time
      constants of left ventricular pressure decline derived from exponential curve
      fits with a zero (Tw) and non-zero (Tb) asymptote pressure in the MI group to the
      same extent as in the control group (4 vs 5 ms, difference not significant [NS],
      and 9 vs 11 ms, NS, respectively). In the PES beat, peak E velocity remained
      unaltered (48 vs 49 cm/s, NS) in the control group, whereas it increased
      significantly (p less than 0.0001) from 47 to 51 cm/s in the MI group.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1998279
TI  - Edge detection versus densitometry for assessing coronary stenting
      quantitatively.
AB  - The optimal method used to analyze quantitatively the immediate angiographic
      results of coronary stenting in the coronary arteries has not been studied.
      Accordingly, minimal luminal cross-sectional area was determined by 2 methods,
      edge detection and densitometry, in 19 patients who underwent percutaneous
      transluminal coronary angioplasty (PTCA) and then coronary stent implantation for
      symptomatic coronary stenoses. The correlation coefficient, 0.73 before
      angioplasty, decreased to 0.59 after coronary angioplasty and then increased to
      0.83 after stent implantation. The mean differences between edge detection and
      densitometric determinations of minimal luminal cross-sectional area were 0.31 +/
      0.51 mm2 before PTCA, -0.38 +/- 1.22 mm2 after angioplasty and 0.35 +/- 0.79 mm2
      after coronary stenting. It is concluded that, although the correlation and
      variability in the measurement of minimal luminal cross-sectional area between
      edge detection and densitometry deteriorate after PTCA, they are improved after
      stenting, probably because of smoothing of the vessel contours by the stent and
      remodeling of the stented segment into a more circular configuration. Therefore,
      in the stented coronary artery, edge detection and densitometry are equally
      acceptable methods of analysis.

PMID- 1998280
TI  - Frequency of success and complications of coronary angioplasty of a stenosis at
      the ostium of a branch vessel.
AB  - The authors of this study hypothesized that percutaneous transluminal coronary
      angioplasty of a stenosis at the ostium of a branch vessel, whether isolated or
      associated with a bifurcation stenosis, was associated with reduced procedural
      success and increased in-hospital complications. One hundred six patients with
      119 ostial branch stenoses were compared with 1,168 patients who underwent
      angioplasty of nonostial branch stenoses. An ostial branch stenosis was defined
      as a stenosis in the proximal 3 mm of a major branch vessel (diagonal [n = 58],
      posterior descending [n = 21], obtuse marginal [n = 34] and intermediate [n =
      6]). The ostial branch stenosis was isolated in 61% of the patients and
      associated with a bifurcation stenosis in 39%. Despite a balloon to artery ratio
      of 1.05:1, angiographic success was 74% of ostial branch stenoses versus 91% of
      nonostial stenoses (p less than 0.01). Furthermore, angioplasty of ostial branch
      stenoses resulted in a complication rate of 13 versus 5% for angioplasty of
      nonostial branch stenoses (p less than 0.01). Therefore, angioplasty of ostial
      branch stenoses results in decreased procedural success and significant residual
      stenosis despite adequate balloon sizing, suggesting arterial elastic recoil and
      a significant increase in complications.

PMID- 1998281
TI  - Comparison of the efficacy of Questran Light, a new formulation of cholestyramine
      powder, to regular Questran in maintaining lowered plasma cholesterol levels.
AB  - Sixty-one men with known hypercholesterolemia (plasma cholesterol greater than
      265 mg/dl), most of whom were previous participants in the Coronary Primary
      Prevention Trial of the U.S. Lipid Research Clinic Program, were chosen to take
      part in this study to test the effectiveness of a new low-calorie (Questran
      Light) cholestyramine formulation against the proven effectiveness of the
      currently marketed formulation Questran in maintaining lowered plasma cholesterol
      levels. The study recorded changes in fasting plasma lipids, total cholesterol,
      high-density lipoprotein cholesterol, triglycerides, and calculated low-density
      lipoprotein cholesterol. After establishing baseline lipid/lipoprotein levels in
      a 3-week period during which all participants received the currently marketed
      formulation, the men were randomized into 2 groups, 1 group (n = 31) taking the
      new Questran Light formulation of 4 g of cholestyramine in 5 g of powder per
      pack, while the other group (n = 30) continued to take the marketed Questran
      formulation of 4 g of cholestyramine in 9 g of powder per pack. Each group
      consumed a total of 24 g/day of cholestyramine in 2 divided doses. At the end of
      the maintenance phase of the study there were no statistically significant mean
      changes in percentage from baseline to end-point lipid/lipoprotein levels within
      either group, nor were there any significant differences between the Questran
      Light group or the currently marketed Questran formulation group. The new low
      calorie cholestyramine formulation appears to be equally as effective in
      maintaining lowered plasma cholesterol levels as the currently marketed
      formulation.

PMID- 1998282
TI  - Characteristics of accessory pathways exhibiting decremental conduction.
AB  - The prevalence, electrophysiologic characteristics and functional significance of
      decremental conduction over an accessory pathway were examined in this
      retrospective study of 653 patients who had an accessory pathway demonstrated at
      electrophysiologic study. Decremental conduction was identified in 50 patients
      (7.6%). In 15 patients with anterograde decremental conduction, the accessory
      pathway was right parietal or septal in 14 patients and left parietal in 1
      patient. In the 40 patients with retrograde decrement, the accessory pathway was
      left parietal in 19, posteroseptal in 13, right parietal in 2 and right
      anteroseptal in 6 patients. Anterograde conduction over the accessory pathway was
      absent in 11 of the 40 patients with retrograde decrement. Retrograde conduction
      over the accessory pathway was absent in 9 patients with anterograde decrement.
      There was no significant difference in the accessory pathway effective refractory
      period, or shortest cycle length with 1:1 conduction over the accessory pathway
      in anterograde and retrograde directions. The shortest RR interval in atrial
      fibrillation between 2 preexcited QRS complexes was longer in patients with
      anterograde decremental conduction than in a control group of patients with
      anterograde-conducting accessory pathways without decremental properties. These
      data demonstrate that decremental conduction over accessory pathways is uncommon.
      Anterograde decremental conduction usually occurs in right-sided or septal
      pathways that often do not conduct in the retrograde direction.

PMID- 1998283
TI  - Doppler echocardiographic comparison of the Carpentier and Duran anuloplasty
      rings versus no ring after mitral valve repair for mitral regurgitation.
AB  - To compare the hemodynamic results of different anuloplasty techniques of primary
      valve repair for mitral regurgitation, 122 patients were prospectively studied
      with Doppler echocardiograms 5 to 10 days after operation. Seventy-seven patients
      had mitral valve prolapse, 27 had coronary artery disease, 13 patients had
      rheumatic mitral valve lesions and 5 patients had infective endocarditis. Forty
      eight patients received the flexible Duran ring, 46 received the more rigid
      Carpentier ring and 28 patients received no ring. Doppler echocardiography
      demonstrated a significant decrease in mitral valve area estimated by the
      pressure half-time method in patients who received either a Carpentier (2.6 +/-
      0.8 cm2) or Duran ring (2.8 +/- 0.8 cm2) when compared with patients who received
      no ring (3.2 +/- 0.7 cm2) (p = 0.01). No significant differences were observed
      for peak transmitral diastolic velocity, peak transmitral diastolic gradient, or
      the grade of mitral regurgitation by color flow Doppler mapping between patients
      with and without rings. The etiology of mitral disease and concomitant surgical
      procedures accompanying mitral valve repair did not significantly influence
      mitral valve area, peak velocity or peak gradient. These data suggest that
      Carpentier and Duran rings decrease the hemodynamic mitral valve area; however,
      the decrease in valve area is small and not associated with a clinically
      important increase in transvalvular gradient.

PMID- 1998284
TI  - Influence of sympathetic stimulation and parasympathetic withdrawal on Doppler
      echocardiographic left ventricular diastolic filling velocities in young normal
      subjects.
AB  - To determine the effects of parasympathetic withdrawal or sympathetic stimulation
      on Doppler echocardiographic measures of left ventricular diastolic filling, we
      studied 10 young normal subjects aged 21 to 29 years during separate infusions of
      atropine (0.8 mg followed by 0.4 mg every 10 minutes until heart rate greater
      than 110 beats/min or a total dose of 2 mg was attained) and epinephrine (10, 25
      and 50 ng/kg/min for 12 minutes each). At the highest atropine dose, heart rate
      increased from 60 +/- 9 to 105 +/- 8 beats/min (mean +/- standard deviation), the
      diastolic filling period decreased by 61% (573 +/- 141 to 222 +/- 34 ms), the
      peak early (E) filling decreased 23% (77 +/- 12 to 61 +/- 11 cm/s), the peak
      atrial (A) filling increased 103% (40 +/- 6 to 81 +/- 17 cm/s), and the E/A ratio
      decreased by 60% (2.0 +/- 0.5 to 0.8 +/- 0.3) (all p less than 0.001). These
      alterations were not correlated to changes in systolic function, preload, blood
      pressure or plasma catecholamines, all of which were unchanged. However, atropine
      induced changes in diastolic filling period were highly correlated to changes in
      E peak (r = 0.64, p less than 0.01), A peak (r = -0.95, p less than 0.001) and
      the E/A ratio (r = 0.93, p less than 0.001). The effects of atropine on the E/A
      ratio were normalized by dividing the E/A ratio by the diastolic filling period
      (E/A/diastolic filling period).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1998285
TI  - Effects of aminophylline on atrioventricular conduction in patients with late
      atrioventricular block during inferior wall acute myocardial infarction.

PMID- 1998286
TI  - Detection of myocardial viability in stunned or hibernating myocardium by delayed
      emptying on radionuclide ventriculography.

PMID- 1998287
TI  - Prognostic significance of hydropericardia and pericardial friction rub in Q-wave
      acute myocardial infarction.

PMID- 1998288
TI  - Influence of gender on inducibility of ventricular arrhythmias in survivors of
      cardiac arrest with coronary artery disease.

PMID- 1998290
TI  - A Doppler echocardiographic examination of the normal aortic valve and left
      ventricular outflow tract.

PMID- 1998289
TI  - Frequency of late potentials in systemic sclerosis.

PMID- 1998291
TI  - A grizzly paradox.

PMID- 1998292
TI  - Preoperative angiography of the internal mammary artery.

PMID- 1998293
TI  - Trifluoperazine and spontaneous contrast.

PMID- 1998294
TI  - Comparison of the four major USA cardiology journals in 1990: a look at 51
      kilograms (112 pounds) of journals and over 15,000 editorial pages.

PMID- 1998295
TI  - An American Board of Orthodontics case report. Correction of a Class III
      mandibular prognathism and asymmetry through orthodontics and orthognathic
      surgery.
AB  - The Class III malocclusion with mandibular prognathism can involve many factors,
      among which are excessive mandibular growth, underdevelopment of the maxilla,
      environmental factors, and trauma to the jaws. The correction of this
      malocclusion can involve an orthodontic or a combined orthodontic-orthognathic
      approach. Skeletal asymmetries can complicate this situation, making treatment
      either more difficult, more complicated, or both. This case presentation involves
      treatment with a combined orthodontic-orthognathic approach. [This case was
      presented to the American Board of Orthodontics in partial fulfillment of the
      requirements for the certification process conducted by the Board.]

PMID- 1998296
TI  - Discovering the uniqueness of the individual.

PMID- 1998297
TI  - Comparison of treatment effects with labial and lingual fixed appliances.
AB  - Pretreatment and posttreatment lateral cephalometric radiographs were evaluated
      for 120 patients--40 from each of three private practices. Twenty patients from
      each office had been treated with labial fixed appliances and 20 with lingual
      fixed appliances. There were no significant differences between labial and
      lingual appliances with respect to the change of any cephalometric measurement
      during treatment (posttreatment value minus pretreatment value). Differences
      among patients from the three offices were found only for upper incisor vertical
      position, and these appeared to reflect differences in treatment objectives
      rather than in appliances. However, several significant differences were found
      when changes during treatment were evaluated according to extraction pattern,
      without reference to the type of appliance used. There was no evidence that the
      mechanics required with lingual appliances necessarily led to any changes in
      treatment results, as determined by the cephalometric measurements used in this
      study.

PMID- 1998298
TI  - Extraction, orthodontic treatment, and craniomandibular dysfunction.
AB  - Signs and symptoms attributed to craniomandibular dysfunction (CMD) were
      registered in the Groningen longitudinal prospective study over a 15-year period.
      It is concluded that none of the three treatment types--removable appliances,
      Begg mechanics, and chin cups--should be considered causal factors for the signs
      and symptoms registered many years later. Furthermore, a comparison was made
      among nonextraction, extraction of all first premolars, and extraction of other
      teeth with regard to CMD and it was concluded that the original growth pattern
      that caused the teeth to be selected for extraction--rather than the extraction
      itself--is the most likely factor responsible for the frequency of CMD reported
      years later. This conclusion agrees with one based on a previously postulated
      idea about the relationship between dysfunction symptoms and growth patterns.

PMID- 1998299
TI  - Mesial force from unerupted third molars.
AB  - Erupting mandibular third molars are implicated as a cause of anterior crowding
      of mandibular teeth. The goal of this two-part investigation was to measure the
      mesial force exerted by unerupted mandibular third molars. We hypothesized that
      such a force increases the tightness of all proximal posterior tooth contacts
      mesial to the mandibular second molar, and that surgical removal of third molars
      relieves the tightness by eliminating this force. The contact tightness between
      mandibular posterior teeth was measured bilaterally in 20 patients with bilateral
      unerupted mandibular third molars, immediately before and after unilateral
      removal of a third molar. We found unexpectedly that mean proximal tightness
      decreased bilaterally in all contacts that were measured after unilateral removal
      of a third molar, and we did not detect a mesial force exerted by unerupted third
      molars. We suspected that this bilateral relief of contact tightness resulted
      from placing the patients in a supine position for surgery. The second part of
      the experiment was conducted to determine the effects of postural change on
      proximal contact tightness where no surgery had been performed. For ten subjects
      we discovered a mean decrease in the tightness of all mandibular posterior
      contacts 2 hours after the patient had been moved from an upright to a supine
      position. The greatest mean decrease (-32%, p less than 0.0001) was found at the
      most posterior tooth contact. We conclude that surgical removal of unerupted
      mandibular third molars does not significantly reduce proximal contact tightness,
      but that simple movement from an upright to a supine position relieves such
      tightness dramatically.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1998300
TI  - Changes in mandibular length before, during, and after successful orthopedic
      correction of Class II malocclusions, using a functional appliance.
AB  - Forty-seven girls were successfully treated with a functional appliance (FA). To
      be included in this study, the rate of increase in mandibular length during
      treatment had to be greater than twice the mean rate for a subgroup of 20 of
      these patients evaluated during a pre-FA observation period. The mean mandibular
      growth rate was 6 mm per year while the FA was activated. In the ensuing months,
      cephalograms were taken at intervals coinciding with five post-FA phases,
      including complete edgewise treatment and retention. During the post-FA phase of
      initial edgewise treatment, the mandibular growth rate was dramatically reduced
      when compared with 47 controls matched for age, sex, and initial SN:GoGn angle.
      Selected individual cases are presented to illustrate the great variability in
      growth responses that were obtained. This study found highly significant
      increases in mandibular length still present 2 years after treatment, diminished
      but still significant gains after 3 years, and no significant difference after 4
      years.

PMID- 1998301
TI  - Heritability of craniometric and occlusal variables: a longitudinal sib analysis.
AB  - There has long been interest in the inheritance of malocclusion, but few studies
      have distinguished between skeletal (craniometric) variables and occlusal, tooth
      based variables (e.g., anterior irregularity, rotations, displacements). This
      study was based on serial assessments of untreated persons in 30 sibships from 4
      years (full deciduous dentition) to 20 years of age (full permanent dentition) in
      the Bolton-Brush Growth Studies of Ohio. Results define a clear dichotomy:
      craniometric variables (k = 29) typically show significant additive components of
      variance; correlations increase from age 4 to age 20; and correlations average
      0.43 at adulthood. Tooth-based variables of position and relationship (k = 21)
      reach significance only occasionally; correlations decrease with age to the
      extent that few variables for subjects at age 20 have a correlation significantly
      different from zero. In contrast to craniometric variables, which have high
      heritabilities, almost all of the occlusal variability is acquired rather than
      inherited.

PMID- 1998302
TI  - Profiling providers of orthodontic services in general dental practice.
AB  - This study was designed to ascertain whether general practitioners who provide
      some orthodontic treatment to a relatively large proportion of their patients
      tend to limit themselves to the treatment of simple cases while they continue to
      refer more difficult cases or whether a high volume of orthodontic treatment is
      linked to an expanded scope of treatment and fewer referrals. Data pertaining to
      volume, scope, and other correlates of orthodontic services in general practice
      were obtained through a survey of dentists currently in general practice in Iowa.
      Of 1159 questionnaires mailed out, 728 (62.8%) were returned. To determine how
      the values of recorded variables differ among the providers of high and low
      volumes of orthodontic services and to determine whether these differences are
      significant, chi 2 tests of independence were calculated. The results obtained
      were used to generate descriptive measures of the profiles of providers of a high
      volume of orthodontic services in general practice. These profiles indicated that
      providers of a high volume of orthodontic treatment (1) performed the same amount
      of limited orthodontic treatment as providers of a low volume of orthodontic
      treatment; (2) performed significantly more major orthodontic treatment; (3) used
      significantly more fixed appliances, functional appliances, and headgears, but
      not removable appliances; (4) took significantly more hours of continuing
      education in orthodontics; and (5) referred significantly fewer patients to
      orthodontic specialists. In view of the projected increase in the amount of
      orthodontics performed in general practice, these findings suggest that, in the
      future, relatively more major orthodontic treatment is likely to be provided by
      general practitioners.

PMID- 1998303
TI  - Molar uprighting with the piggyback buccal sectional arch wire technique.
AB  - This article describes an orthodontic mechanical variation to unlock and upright
      mandibular impacted second permanent molars. This is accomplished with a small
      sectional arch wire that is ligated in a piggyback fashion to the existing arch
      wire and first molar band attachment. The piggyback buccal sectional arch wire
      (PBBSAW) technique provides a simple, expedient, and effective mechanical
      approach to the impacted second molar problem.

PMID- 1998304
TI  - Legal aspects of orthodontic practice: risk management concepts. Written
      treatment requests avoid problems.

PMID- 1998305
TI  - Use of intravenous albumin in the critically ill patient.
AB  - The experimental data supporting and opposing the use of intravenous albumin in
      various groups of patients are provided, and conclusions are drawn from these
      data. The metabolism and kinetics of albumin are reviewed, and the importance of
      albumin levels in critically ill patients is discussed. The reviewed literature
      supports the conclusion that in most critically ill patients, intravenous albumin
      does not improve outcome.

PMID- 1998306
TI  - Bowel rest or bowel starvation: defining the role of nutritional support in the
      treatment of inflammatory bowel diseases.

PMID- 1998307
TI  - Diltiazem therapy for symptoms associated with nutcracker esophagus.
AB  - A randomized double-blind, cross-over prospective trial in 22 patients was
      designed to evaluate possible effect of an oral calcium channel blocker,
      diltiazem, on symptoms of chest pain and/or dysphagia in patients with nutcracker
      esophagus. We studied 22 consecutive patients referred to an esophageal
      diagnostic center for evaluation of noncardiac chest pain or dysphagia having
      high amplitude esophageal contractions, 14 of whom completed the study. Diltiazem
      (60-90 mg qid) was compared with placebo, each being administered for 8 wk.
      Patients were evaluated with esophageal motility pre- and posttreatment periods
      and with regular symptom assessment throughout each 8-wk treatment. Active
      diltiazem therapy resulted in significantly lower (p less than 0.05) mean distal
      esophageal peristaltic pressure (128 +/- 20 mm Hg; +/- SE) than placebo (158 +/-
      16 mm Hg). Mean chest pains scores were significantly (p less than 0.05) lower
      with diltiazem therapy than with placebo. Only nine of the 14 patients fulfilled
      presently acceptable criteria for diagnosing nutcracker esophagus, and the
      diltiazem effect was similar, although not significant, because of the smaller
      sample. CONCLUSIONS: In this preliminary study involving 14 patients, the oral
      calcium channel blocker, diltiazem, appeared to improve noncardiac chest pain
      associated with strong esophageal contraction, the nutcracker esophagus. These
      improved symptoms were associated with significant decreases in contraction
      pressure.

PMID- 1998308
TI  - Colon interposition for esophageal disease: histologic finding of colonic mucosa
      after a follow-up of 5 months to 15 years.
AB  - Thirty-six patients, subjected to colon interposition for benign esophageal
      disease or carcinoma of the esophagus or gastric cardia, were studied by
      endoscopy for signs of mucosal disease in the interposed colon. Five months to 15
      yr (mean 57 months) after the operation, endoscopic finding of the interposed
      colon was macroscopically normal in 28 patients. Signs of inflammation, including
      hyperemia or hyperemia and friability, were observed in seven patients.
      Histologic specimens obtained at endoscopy were examined microscopically, and the
      findings were compared with those seen in the preoperative graft. In two
      patients, chronic inflammatory changes were observed in the graft mucosa,
      consisting of mononuclear cell infiltration of the lamina propria accompanied by
      crypt dilatation and deformation. In one of these patients, the inflammation was
      in the proximal third of the graft, and it was also seen at the endoscopy. In the
      remaining 34 patients, the graft mucosa was microscopically comparable to normal.
      The alterations were unexpectedly few and mild considering the marked change in
      the location and function of the colonic segment.

PMID- 1998310
TI  - The perception of life events and daily stress in nonulcer dyspepsia.
AB  - Previous studies on the association of nonulcer dyspepsia with major life events
      were performed without emphasis on the perception of these events, and have
      yielded conflicting results. The present study examined the perception of life
      events and, in addition, the role of daily "hassles" (stressful events) in
      patients with nonulcer dyspepsia. Thirty-three dyspeptic patients as defined by
      normal endoscopy and ultrasonogram and 33 controls of comparable sex, age, and
      social class were recruited for study. Both groups were asked to select from 56
      major life events those they had experienced and to give a rating on how they
      perceived them. They were further asked to select similarly from 117 items of
      daily stress and to rate the severity of each item. The results demonstrated that
      the number of positive and negative events and the positive score were similar in
      both dyspeptic patients and controls, but dyspeptic patients had a higher
      perceived magnitude of negative events and a higher score of total life change as
      given by the summation of magnitude of positive and negative events (both p less
      than 0.05). The "hassles" scores were not significantly different between
      dyspeptic patients and controls. Analysis of individual life events revealed that
      dyspeptic patients had significantly (p less than 0.05) higher scores than
      controls in items of minor law violations, major change in closeness of family
      members, and major personal illness or injury. We conclude that patients with
      nonulcer dyspepsia have higher negative perception of major life events, which
      indicates that psychological factors may play a role in the pathogenesis of
      nonulcer dyspepsia.

PMID- 1998309
TI  - A topographical relationship between Helicobacter pylori and gastritis:
      quantitative assessment of Helicobacter pylori in the gastric mucosa.
AB  - A topographical relationship between the number of Helicobacter pylori in the
      gastric mucosa and the histological severity of gastritis was studied in 902
      pairs of biopsy specimens taken from 314 patients. A pair of biopsies were taken
      from the antrum, the lesser curvature of the middle body, and the greater
      curvature of the upper body of the stomach. The quantitative assessment of H.
      pylori was made based on smear, culture, and tissue section. The histological
      severity of gastritis was assessed as to the degrees of mononuclear cell and
      polymorphonuclear leukocyte infiltration. A positive correlation was confirmed
      between the number of H. pylori and the severity of polymorphonuclear leukocyte
      infiltration. The degrees of inflammatory cells infiltration in the specimens
      with H. pylori colonization were significantly lower in the upper body than in
      the antrum.

PMID- 1998311
TI  - Immunohistochemical characterization of microvascular endothelial cells in
      primary B cell lymphoma of the gastrointestinal tract.
AB  - Microvascular endothelial cells (EnC) in primary B cell lymphoma of the
      gastrointestinal tract were immunohistochemically studied. Based on the
      morphological structure, the microvasculatures were divided into high endothelial
      cell vessels (HEV) and flat endothelial cell vessels (FEV). There were distinct
      phenotypic differences between HEV and FEV in lymphoma tissues. HEV were
      characterized as OKM1- OKM5-, accompanied by the cluster of non-neoplastic T
      lymphocytes, and FEV were OKM1- OKM5+ not accompanied by T lymphocyte
      infiltration. Factor VIII-related antigen was clearly identified in both EnC, and
      major histocompatibility complex (MHC) class II antigens and interleukin 1 were
      absent or only faintly visible on EnC in lymphoma tissues, whereas they were
      expressed on EnC in non-lymphoma tissues. These findings suggest that
      microvascular EnC in primary B cell lymphoma of the gastrointestinal tract lack a
      property as antigen-presenting cells, and that HEV are involved in the migration
      of non-neoplastic T lymphocytes.

PMID- 1998312
TI  - The role of the physician in the late diagnosis of primary malignant tumors of
      the small intestine.
AB  - Survival from primary malignancies of the small intestine has not improved during
      the last four decades. One reason for this is the advanced stage of disease at
      the time of surgery. In order to determine why diagnosis is made late, we
      reviewed the records of all patients with small bowel malignancy diagnosed
      between 1967 and 1988. The time from the onset of symptoms to the first medical
      contact and the time from medical contact until diagnosis were evaluated in 77
      patients. The average delay in diagnosis attributable 1) to the patient failing
      to report symptoms was less than 2 months, 2) to the physician not ordering the
      appropriate diagnostic test was 8.2 months, and 3) to the radiologist failing to
      make the diagnosis was 12 months. Thus, the major delay in diagnosis was after
      medical help was sought and not from the onset of symptoms to first medical
      consultation. Physicians must increase their sensitivity to the subtle but
      persistent symptoms that necessitate a small bowel evaluation.

PMID- 1998313
TI  - Gluten challenge in patients with celiac disease: evaluation of alpha 1
      antitrypsin clearance.
AB  - Our aim in this study was to monitor changes of the intestinal structure by alpha
      1-antitrypsin clearance (alpha 1-ATCL) in order to offer an alternative to the
      gluten challenge biopsy. In addition, we evaluated the possibility of reducing
      the time of gluten challenge. Twelve patients had a presumptive diagnosis of
      celiac disease based on clinical and histological grounds. They were studied when
      the jejunal histology was normal after gluten-free diet and an alpha 1-ATCL was
      normal. The gluten was introduced by returning to a normal diet. The challenge
      lasted 4 wk. We measured alpha 1-ATCL at the end of the 1st and 4th wk, and a new
      jejunal biopsy was obtained at the end of the 4th wk. By wk 1, alpha 1-ATCL was
      abnormal in 11 patients but normal in one. By wk 4, alpha 1-ATCL was abnormal in
      10 patients and still normal in one. The post-challenge biopsies showed atrophy
      in 11 and was normal only in the patient with normal alpha 1-ATCL at wk 1 and 4.
      One patient with abnormal alpha 1-ATCL had to stop the challenge at the first
      week. The patient with normal clearance at wk 1 and 4 and normal biopsy at wk 4
      had abnormal results at 6 months. These data support our hypothesis that alpha 1
      ATCL can be used as evidence of gluten toxicity after gluten challenge, and that
      this test can be abnormal as early as 1 wk after gluten is reintroduced.

PMID- 1998314
TI  - Prolonged treatment of children with chronic hepatitis B with recombinant alpha
      2a-interferon: a controlled, randomized study.
AB  - A prospective study was conducted to evaluate the efficacy and tolerance of alpha
      interferon in 20 children with biopsy-proven HBsAg/HBeAg/HBV-DNA-positive, anti
      delta-negative chronic hepatitis. Patients were randomized to receive alpha 2a
      interferon (INF), 3 MU im three times weekly for 12 months, or no treatment (10
      patients per group). Five patients receiving IFN showed a marked decrease or
      negativization of HBV-DNA during treatment. At the end of the study (after 18
      month), three patients lost HBV-DNA permanently, and two of them seroconverted to
      HBeAb 10 and 11 months after disappearance of HBV-DNA with normalization of
      aminotransferase values. In the control group, one patient had spontaneous
      clearance of HBV-DNA with conversion to HBeAb and normalization of
      aminotransferase levels. All treated patients had a febrile reaction in the first
      month of treatment. The dose of IFN had to be decreased in two patients and was
      discontinued for persistent intolerance in one of them. Patients who showed a
      decreased viral replication had higher initial biochemical and histological
      activity than nonresponders. The data suggest that IFN treatment may favorably
      influence the progression of chronic B hepatitis in children with a history of
      acute hepatitis and active chronic disease.

PMID- 1998315
TI  - Cluster of fulminant hepatitis B in crack users.
AB  - Fulminant hepatitis occurs in only 1% of acute hepatitis B patients, requiring
      hospitalization, but coinfection with delta virus increases the incidence.
      Hepatitis B and D infection are commonly associated with intravenous drug abuse,
      but there have been no previous reports of an association with nonparenteral
      cocaine. Crack use, via sexual promiscuity, is associated with an increased risk
      for human immunodeficiency virus infection, but has never been associated with
      viral hepatitis. We report four fatal cases of fulminant hepatitis B including,
      one with delta virus coinfection and one with human immunodeficiency virus (HIV)
      infection, in young, sexually active, heterosexual crack users. These patients
      denied a history of intravenous drug abuse. Our patients probably contracted
      hepatitis B infection via heterosexual contact. Chronic cocaine exposure may or
      may not have contributed to the fulminant outcome. Crack users may be at
      increased risk of developing hepatitis B and D infection. Epidemiological studies
      are needed to evaluate their risk of viral hepatitis and the effect of cocaine on
      its outcome.

PMID- 1998316
TI  - Gaucher's disease complicated by bleeding esophageal varices and colonic
      infiltration by Gaucher cells.
AB  - We report a 10-yr-old child with Gaucher's disease who developed upper
      gastrointestinal bleeding from esophageal varices, as well as hemorrhage from a
      colonic polyp infiltrated with Gaucher cells. Both the varices and polyp were
      treated endoscopically, and the outcome was successful. Although gastrointestinal
      hemorrhage due to portal hypertension is considered a rare complication of
      Gaucher's disease, colonic infiltration with Gaucher cells has not been
      recognized previously.

PMID- 1998317
TI  - Use of plasmid profiles in the investigation of a patient with Helicobacter
      pylori infection and peptic ulcer disease.
AB  - Plasmids may effect bacterial virulence and antibiotic resistance, and serve as
      epidemiologic markers. In this study, plasmid DNA profiles of serial isolates of
      Helicobacter pylori showed persistence of an identical strain of this organism in
      a patient with duodenal ulcer disease. Three control strains of H. pylori
      isolated from other patients contained plasmids different from each other and
      from that of the original patient; two of these strains had two plasmids each.
      These data have important implications for further study of the epidemiology and
      pathogenesis of H. pylori-related diseases.

PMID- 1998318
TI  - Peritoneal blastomycosis.
AB  - Blastomycosis is a systemic fungal infection caused by Blastomyces dermatitidis.
      Involvement of the peritoneum is unusual, with only two previously reported cases
      that occurred in association with disseminated disease. A single case of
      histopathologically proven blastomycosis involving the peritoneum is presented,
      as well as a short overview of previously published cases on gastrointestinal and
      peritoneal blastomycosis. The case is unique in that chronic peritonitis was the
      only manifestation of disease. The diagnosis was made by laparoscopy.

PMID- 1998319
TI  - Ehlers-Danlos syndrome type IV: diagnosis and therapy of associated bowel
      perforation.
AB  - Ehlers-Danlos syndrome type IV is a heritable disease of type III collagen
      metabolism. This diagnosis is suspected in a patient with a combination of
      clinical manifestations and family history, but it is confirmed only by culture
      of the patient's skin fibroblasts and demonstration of a defect in type III
      collagen metabolism. The disease may rarely present with spontaneous colonic
      perforation, a complication traditionally treated by primary closure of the
      perforated segment and creation of an end colostomy. Attempts at bowel
      reanastomosis have often resulted in repeated colon perforations. We present the
      first patient with Ehlers-Danlos type IV syndrome to develop a colon perforation
      proximal to an end colostomy, and discuss the surgical strategy to prevent
      recurrences of this and other postoperative complications associated with the
      syndrome.

PMID- 1998320
TI  - Perforation and tumor formation of the intestine in primary amyloidosis.
AB  - We report a case of primary amyloidosis with repeated bowel perforations. This
      patient also had localized amyloid deposition creating a tumorous region
      mimicking malignancy in the rectum. Perforation of the intestine is common in
      systemic amyloidosis. The ischemic change due to amyloid infiltration into the
      vessel wall may lead to perforation of the affected bowel. Amyloid tumors occur
      more often in localized amyloid than in systemic amyloidosis. Macroscopically, it
      is difficult to distinguish amyloid tumor of the intestine from neoplasia.

PMID- 1998321
TI  - Cerebrovascular complications of inflammatory bowel disease.
AB  - There is an increased incidence of central nervous system thromboembolic events
      in young patients with inflammatory bowel disease. A 33-yr-old woman previously
      diagnosed with pseudotumor cerebri suffered superior sagittal and transverse
      sinus thromboses during a severe flare of ulcerative colitis. These were
      documented on contrast computed tomographic (CT) and magnetic resonance imaging
      (MRI) scans. Stroke may be more common in patients with ulcerative colitis than
      in patients with Crohn's disease; arterial disease is more prevalent than venous
      and dural sinus disease, and is correlated with an active phase of inflammatory
      bowel disease. It is difficult to assess whether there is a relationship to
      concurrent steroid use, and a consistent relationship to duration of inflammatory
      bowel disease or to other extraintestinal manifestations is not apparent.

PMID- 1998322
TI  - The value of HIDA imaging in acalculous right upper quadrant pain: "Spin the
      wheel, Vanna"!

PMID- 1998323
TI  - Gastroesophageal reflux aspiration management--is there a tarnish on cold steel?

PMID- 1998324
TI  - Giant fibrous mesothelioma of the liver.

PMID- 1998325
TI  - A simplified technique for accurate placement of ambulatory pH probes.

PMID- 1998326
TI  - Through-the-nose gastroscopy.

PMID- 1998327
TI  - Osseous metaplasia in colonic adenocarcinoma.

PMID- 1998328
TI  - Peritoneal encapsulation of the small bowel: a rare cause of intestinal
      obstruction.

PMID- 1998329
TI  - Prenatal screening for hemoglobinopathies.

PMID- 1998330
TI  - Prenatal screening for hemoglobinopathies. I. A prospective regional trial.
AB  - Prenatal hemoglobinopathy screening was chosen as a model system for the study of
      patient receptivity to unsolicited genetic information. Providers of prenatal
      care in Rochester, NY, were offered free testing of all their prenatal patients
      and genetic counseling of women found positive. The 18,907 prenatal samples
      tested in a 5-year period represented 35.1% of the pregnancies in the Rochester
      metropolitan region. A hemoglobinopathy was found in 810 pregnancies (4.3%). Of
      the 21 different types of hemoglobinopathies detected, the most common were
      sickle cell trait (59%), hemoglobin C trait (19%), beta-thalassemia trait (11%),
      and hemoglobin E trait (5%). At the time of phlebotomy, 75% of the pregnancies
      were of less than 18 wk duration. Sixty-six percent of the pregnancies occurred
      in patients unaware of their diagnosis, and 80% occurred in patients unaware that
      they might be at risk for a child with a serious blood disorder. Of the 810
      positive pregnancies, 551 (68%) occurred in patients who came for counseling. Of
      453 women counseled during their first screened pregnancy, 390 (86%) said they
      wanted their partners tested and 254 (55%) had their partner tested. In the 77
      pregnancies thus found to be at risk, the couple was too late for prenatal
      diagnosis in 12 cases, and the condition for which the fetus was at risk was too
      mild in 12 cases. Prenatal diagnosis was offered in the remaining 53 pregnancies
      and was accepted by 25 couples (47%). These results indicate that unselected
      patients in the primary care setting in this region, even though pregnant, are
      receptive to and utilize genetic information.

PMID- 1998331
TI  - Prenatal screening for hemoglobinopathies. II. Evaluation of counseling.
AB  - Learning during genetic counseling is often below expectations, especially in the
      context of genetic screening. In this report we describe learning as a result of
      genetic counseling of 298 pregnant women identified as hemoglobinopathy carriers,
      234 with sickle cell trait and 64 with beta-thalassemia trait. Counseling was
      designed to provide the information needed in a simple, clear, and nondirective
      manner. A special videotape produced for this purpose provided dramatization and
      a role model illustrating an appropriate response. After viewing the videotape
      the counselee had an opportunity to question the counselor and to have any
      misconceptions corrected. Questionnaires revealed significantly increased
      knowledge as a result of counseling in each of the three hemoglobinopathy subject
      areas tested-namely, clinical manifestations, genetics, and prenatal diagnosis.
      Five factors correlated with higher knowledge scores after counseling-namely, a
      younger patient age, more years of education, knowledge of having trait before
      this identification, knowledge of the baby's father having trait before
      counseling, and having no prior children.

PMID- 1998332
TI  - Prenatal screening for hemoglobinopathies. III. Applicability of the health
      belief model.
AB  - A comprehensive prenatal hemoglobinopathy screening program in Rochester, NY, has
      been described in a preceding paper in this issue of the Journal. A woman
      identified as a carrier may face three decisions. The first is whether to accept
      the offer of counseling. The second is whether to have her partner tested. If her
      partner also tests positive, then the third decision is whether to accept the
      offer of prenatal diagnosis. This report analyzes factors affecting her decision,
      with special attention being given to factors invoked by the Health Belief Model.
      Factors predicting that a patient who we identified as a carrier would come for
      counseling included the following: patient had no prior knowledge that she is a
      carrier (P less than .001), a gestational age less than 18 wk (P less than .01),
      and Caucasian race (P less than .05). For sickle cell trait counselees and beta
      thalassamia trait counselees, factors found to predict patient's intent to have
      partner tested were the following: a greater postcounseling knowledge of the
      disease (P less than .009), a lesser perceived burden of intervention (P less
      than .011), and belief that the partner is also a carrier (P less than .008).
      Also for sickle cell trait counselees and beta-thalassemia trait counselees,
      factors predicting that the partner actually will be tested were the following:
      living with the partner (P less than .001), gestational age at identification
      less than or equal to 18 wk (P less than .001), a lesser perceived burden of
      intervention (P less than .002), and a greater perceived seriousness of the
      disease (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1998333
TI  - Assignment of Emery-Dreifuss muscular dystrophy to the distal region of Xq28: the
      results of a collaborative study.
AB  - Emery-Dreifuss muscular dystrophy (EDMD) is an X-linked humeroperoneal dystrophy
      associated with cardiomyopathy that is distinct from the Duchenne and Becker
      forms of X-linked muscular dystrophy. Linkage analysis has assigned EDMD to the
      terminal region of the human X chromosome long arm. We report here further
      linkage analysis in two multigenerational EDMD families using seven Xq28 marker
      loci. Cumulative lod scores suggest that EDMD is approximately 2 cM from DXS52
      (lod = 15.67) and very close to the factor VIII (F8C) and the red/green color
      pigment (R/GCP) loci, with respective lod scores of 9.62 and 10.77, without a
      single recombinant. Several recombinations between EDMD and three proximal Xq28
      markers suggest that the EDMD gene is located in distal Xq28. Multipoint linkage
      analysis indicates that the odds are 2,000:1 that EDMD lies distal to DXS305.
      These data substantially refine the ability to perform accurate carrier
      detection, prenatal diagnosis, and the presymptomatic diagnosis of at-risk males
      for EDMD by linkage analysis. The positioning of the EDMD locus close to the loci
      for F8C and R/GCP will assist in future efforts to identify and isolate the
      disease gene.

PMID- 1998334
TI  - Mapping of the locus for X-linked cardioskeletal myopathy with neutropenia and
      abnormal mitochondria (Barth syndrome) to Xq28.
AB  - X-linked cardioskeletal myopathy with neutropenia and abnormal mitochondria is
      clinically characterized by congenital dilated cardiomyopathy, skeletal myopathy,
      recurrent bacterial infections, and growth retardation. We analyzed linkage
      between the disease locus and X-chromosomal markers in a family with seven
      carriers, four patients, and eight unaffected sons of carriers. Highest lod
      scores obtained by two-point linkage analysis were 2.70 for St14.1 (DXS52, TaqI)
      at a recombination fraction of zero and 2.53 for cpX67 (DXS134) at a
      recombination fraction of zero. Multipoint linkage analysis resulted in a maximum
      lod score of 5.24 at the position of St35.691 (DXS305). The most distal
      recombination detected in this family was located between the markers II-10
      (DXS466) and DX13 (DXS15). These data indicate the location of the mutated gene
      at Xq28.

PMID- 1998335
TI  - Optic atrophy in Leber hereditary optic neuroretinopathy is probably determined
      by an X-chromosomal gene closely linked to DXS7.
AB  - Leber hereditary optic neuroretinopathy (LHON) is a maternally inherited disease,
      probably transmitted by mutations in mtDNA. The variation in the clinical
      expression of the disease among family members has remained unexplained, but
      pedigree data suggest an involvement of an X-chromosomal factor. We have studied
      genetic linkage of the liability to develop optic atrophy to 15 polymorphic
      markers on the X chromosome in six pedigrees with LHON. The results show evidence
      of linkage to the locus DXS7 on the proximal Xp. Tight linkage to the other
      marker loci was excluded. Multipoint linkage analysis placed the liability locus
      at DXS7 with a maximum lod score (Zmax) of 2.48 at a recombination fraction
      (theta) of .0 and with a Zmax - 1 support interval theta = .09 distal to theta =
      .07 proximal of DXS7. No evidence of heterogeneity was found among different
      types of families, with or without a known mtDNA mutation associated with LHON.

PMID- 1998336
TI  - mtDNA depletion with variable tissue expression: a novel genetic abnormality in
      mitochondrial diseases.
AB  - We studied two related infants with a fatal mitochondrial disease, affecting
      muscle in one and liver in the other. Quantitative analysis revealed a severe
      depletion of mtDNA in affected tissues. This genetic abnormality was also
      observed in muscle of an unrelated infant with myopathy and in muscle and kidney
      of a fourth child with myopathy and nephropathy. Biochemistry,
      immunohistochemistry, and in situ hybridization showed that the depletion of
      mtDNA in muscle fibers was correlated with a respiratory chain defect and with
      lack of mitochondrially translated proteins. Although the differential tissue
      involvement in these infants suggests mtDNA heteroplasmy, sequence analysis of
      mtDNA replication origins did not reveal any abnormality that could account for
      the low copy number.

PMID- 1998337
TI  - Characterization of a large deletion associated with a polymorphic block of
      repeated dinucleotides in the type III procollagen gene (COL3A1) of a patient
      with Ehlers-Danlos syndrome type IV.
AB  - Ehlers-Danlos syndrome type IV (EDS IV) is an autosomal dominant condition
      characterized by extreme fragility of skin, blood vessels, intestine, gravid
      uterus, and lungs. The phenotype is accounted for by mutations affecting the
      integrity and/or synthesis of the precursor procollagen molecules of type III
      collagen. In this article, we report the elucidation of the molecular defect in
      an EDS IV patient whose type III collagen was previously found to be structurally
      abnormal. We utilized PCR in a two-step process involving first the localization
      of the mutation in the mRNA and then the characterization of the defect in the
      gene. The results established the patient's heterozygosity for a genomic deletion
      of about 7.5 kb which eliminates 1,026 nucleotides of coding sequences in the
      message. The mutation arose as a result of an exon-to-intron recombination. The
      deleted segment extends from the 13th nucleotide of exon 9 to within a DNA
      sequence of intron 24, which is composed of a series of dinucleotide repeats.
      Using PCR, we tested the polymorphic nature of this DNA element on several
      unrelated individuals. Analysis of amplified genomic products of 45 chromosomes
      recognized at least four distinct allelic forms that display frequencies ranging
      from 5% to 61%. Mendelian segregation of three of the four alleles was
      established by the same method in a 3-generation family.

PMID- 1998338
TI  - Cloning and expression of the cDNA encoding human fumarylacetoacetate hydrolase,
      the enzyme deficient in hereditary tyrosinemia: assignment of the gene to
      chromosome 15.
AB  - Type 1 hereditary tyrosinemia (HT) is an autosomal recessive disease
      characterized by a deficiency of the enzyme fumarylacetoacetate hydrolase (FAH;
      E.C.3.7.1.2). We have isolated human FAH cDNA clones by screening a liver cDNA
      expression library using specific antibodies and plaque hybridization with a rat
      FAH cDNA probe. A 1,477-bp cDNA was sequenced and shown to code for FAH by an in
      vitro transcription-translation assay and sequence homology with tryptic
      fragments of purified FAH. Transient expression of this FAH cDNA in transfected
      CV-1 mammalian cells resulted in the synthesis of an immunoreactive protein
      comigrating with purified human liver FAH on SDS-PAGE and having enzymatic
      activity as shown by the hydrolysis of the natural substrate fumarylacetoacetate.
      This indicates that the single polypeptide chain encoded by the FAH gene contains
      all the genetic information required for functional activity, suggesting that the
      dimer found in vivo is a homodimer. The human FAH cDNA was used as a probe to
      determine the gene's chromosomal localization using somatic cell hybrids and in
      situ hybridization. The human FAH gene maps to the long arm of chromosome 15 in
      the region q23-q25.

PMID- 1998339
TI  - Thermolabile methylenetetrahydrofolate reductase: an inherited risk factor for
      coronary artery disease.
AB  - Severe methylenetetrahydrofolate reductase (MTHFR) deficiency with less than 2%
      of normal enzyme activity is characterized by neurological abnormalities,
      atherosclerotic changes, and thromboembolism. We have discovered a "new" variant
      of MTHFR deficiency which is characterized by the absence of neurological
      abnormalities, an enzyme activity of about 50% of the normal value, and
      distinctive thermolability under specific conditions of heat inactivation. In
      this study, lymphocyte MTHFR specific activities in the thermolabile variant and
      control groups were 5.58 +/- 0.91 and 10.33 +/- 2.89 nmol formaldehyde formed/mg
      protein/h, respectively. The difference was significant (P less than .01).
      However, there was overlap among the individual values from the two groups. On
      the other hand, residual MTHFR activity after heat inactivation was 11.2 +/-
      1.43% in the thermolabile variant and 36.3 +/- 5.18% in the controls. There was
      no overlap. Enzyme studies in 10 subjects with thermolabile MTHFR and their
      family members support the hypothesis that thermolabile MTHFR is inherited as an
      autosomal recessive trait. To elucidate the association of thermolabile MTHFR
      with the development of coronary artery disease, we determined the
      thermostability of lymphocyte MTHFR in 212 patients with proven coronary artery
      disease and in 202 controls without clinical evidence of atherosclerotic vascular
      disease. Thermolabile MTHFR was found in 36 (17.0%) cardiac patients and 10
      (5.0%) controls. The difference in incidence between the two groups was
      statistically significant (P less than .01). The average age at onset of clinical
      coronary artery disease in 36 patients with thermolabile MTHFR was 57.3 +/- 7.6
      years (35-72 years). The mean total plasma homocysteine concentration in patients
      with thermolabile MTHFR was 13.19 +/- 5.32 nmol/ml and was significantly
      different from the normal mean of 8.50 +/- 2.80 nmol/ml (P less than .05). There
      was no association between thermolabile MTHFR and other major risk factors. We
      conclude that thermolabile MTHFR is a variant(s) of MTHFR deficiency which is
      inherited as an autosomal recessive trait. In addition, it is positively
      associated with the development of coronary artery disease. Determination of in
      vitro thermostability of lymphocyte MTHFR is a reliable method for identifying
      subjects with this abnormality.

PMID- 1998340
TI  - Intermediate hyperhomocysteinemia resulting from compound heterozygosity of
      methylenetetrahydrofolate reductase mutations.
AB  - Four subjects with thermolabile methylenetetrahydrofolate reductase (MTHFR) were
      discovered among 16 "obligate" heterozygotes for severe MTHFR deficiency and
      their family members. All four subjects had less than 25% of normal mean MTHFR
      specific activity in lymphocyte extracts. Three of them with normal serum folate
      and cyanocobalamin had intermediate hyperhomocysteinemia, and one with high serum
      folate and cyanocobalamin had no excessive accumulation of serum homocysteine.
      The biochemical features in these four subjects are distinguishable from subjects
      homozygous for the thermolabile MTHFR, whose specific activity is approximately
      50% of the normal mean, and from heterozygotes for severe MTHFR deficiency, in
      whom the enzyme is thermostable and has a specific activity of about 50% of the
      normal mean. We propose that these four subjects are genetic compounds of the
      allele for the severe mutation and the allele for thermolabile mutation of the
      MTHFR gene. It is postulated that subjects with this genetic compound are more
      susceptible to the development of intermediate hyperhomocysteinemia despite
      normal folate and B12 levels. Nonetheless, hyperhomocysteinemia due to this
      compound heterozygosity is correctable by oral folic acid therapy.

PMID- 1998341
TI  - Diagnosis of heterozygous states for adenine phosphoribosyltransferase deficiency
      based on detection of in vivo somatic mutants in blood T cells: application to
      screening of heterozygotes.
AB  - An accurate diagnosis of heterozygotes for autosomal recessive disorders with
      unknown mutations can be difficult. Using a unique phenomenon occurring in vivo,
      we designed a method for the diagnosis of heterozygotes for adenine
      phosphoribosyltransferase (APRT) deficiency which makes way for a qualitative
      distinction between normal and heterozygous subjects. We cultured peripheral
      blood mononuclear cells with 2,6-diaminopurine, an APRT-dependent cytotoxin, to
      search for in vivo mutational cells. Fifteen putative heterozygotes examined were
      found to possess such mutant cells at rather high frequencies; thus, a false
      negative diagnosis is unlikely. The analysis of genomic DNA in 82 resistant
      clones from two of the heterozygotes clarified that 64 (78%) had lost the
      germinally intact alleles. Thirteen members of APRT-deficient families were
      examined; eight proved to be heterozygotes. Among 425 individuals from two
      separate residential areas of Japan, two heterozygotes were found. The
      authenticity of the heterozygosity was validated by two separate methods for the
      two heterozygotes; hence, a false positive diagnosis can be ruled out. Our data
      showed a calculated heterozygote frequency of 0.47% (95% confidence limits; 0.05%
      1.7%), a value compatible with that (1.2%) calculated from data concerning the
      incidence of 2,8-dihydroxyadenine urolithiasis. This novel genetic approach for
      identifying heterozygotes is now being tested to search for other enzyme
      deficiencies in humans.

PMID- 1998343
TI  - A mutation in the second nucleotide binding fold of the cystic fibrosis gene.
AB  - The discovery last year of the deletion of a phenylalanine residue at amino acid
      position 508 of the cystic fibrosis (CF) gene has meant that approximately 70% of
      mutant chromosomes associated with CF can be accounted for. We report the finding
      of a substitution at nucleotide position 4041 of the CF gene, resulting in a
      change from asparagine to lysine at amino acid position 1303. We believe that
      this is a disease-causing mutation, as it involves a nonconservative amino acid
      change and has only been found on CF chromosomes with a consistent haplotype
      background. The mutation was detected using direct sequencing of PCR-amplified
      genomic DNA and was confirmed by dot hybridization to both normal and mutant
      allele-specific oligonucleotides. The mutation was detected on three chromosomes
      from four individuals but not on any normal chromosome. Its presence in the
      heterozygous state is not correlated with the clinical status of the individual
      patients.

PMID- 1998342
TI  - Linkage analysis of familial Alzheimer disease, using chromosome 21 markers.
AB  - Chromosome 21 markers were tested for linkage to familial Alzheimer disease (FAD)
      in 48 kindreds. These families had multiple cases of Alzheimer disease (AD) in 2
      or more generations with family age-at-onset means (M) ranging from 41 to 83
      years. Included in this group are seven Volga German families which are thought
      to be genetically homogeneous with respect to FAD. Autopsy documentation of AD
      was available for 32 families. Linkage to the 21 q11-q21 region was tested using
      D21S16, D21S13, D21S110, D21S1/S11, and the APP gene as genetic markers. When
      linkage results for all the families were summed, the LOD scores for these
      markers were consistently negative and the entire region was formally excluded.
      Linkage results were also summed for the following family groups; late-onset (M
      greater than 60), early-onset (M less than or equal to 60), Volga Germans (M =
      56), and early-onset non-Volga Germans (M less than or equal to 60). For the
      first three groups, LOD scores were negative for this region. For the early-onset
      non-Volga German group (six families), small positive LOD scores of Zmax = 0.78
      (recombination fraction theta = .15), Zmax = 0.27 (theta = .15), and Zmax = 0.64
      (theta = .0), were observed for D21S13, D21S16, and D21S110, respectively. The
      remainder of the long arm of chromosome 21 was tested for linkage to FAD using
      seven markers spanning the q22 region. Results for these markers were also
      predominantly negative. Thus it is highly unlikely that a chromosome 21 gene is
      responsible for late-onset FAD and at least some forms of early-onset FAD
      represented by the Volga German kindreds.

PMID- 1998344
TI  - Rapid detection of CA polymorphisms in cloned DNA: application to the 5' region
      of the dystrophin gene.
AB  - To identify CA repeats in genomic sequences which had been previously subcloned
      into plasmids, we performed PCR using a (CA)n primer and a flanking vector primer
      on the genomic inserts. By incorporation of a restriction enzyme site into the
      (CA)n primer, we have been able to subclone the genomic DNA so that the sequence
      flanking the CA repeat is readily determined. Primers can then be designed to
      amplify across the CA repeat in patient DNA samples. Application of this
      technique to genomic DNAs surrounding the upstream "brain" promoter of the
      dystrophin gene has led to the discovery of four new CA repeats. Three of these
      repeats are highly polymorphic, with PICs ranging from .586 to .768. The location
      of these markers at the extreme 5' terminus of the dystrophin gene, together with
      their high degree of polymorphism and ease of assay, makes them ideal for linkage
      analysis in families with Duchenne muscular dystrophy.

PMID- 1998345
TI  - Identification of a novel phenylketonuria (PKU) mutation in the Chinese: further
      evidence for multiple origins of PKU in Asia.
AB  - A novel mutation has been identified in the human phenylalanine hydroxylase (PAH)
      gene of a Chinese patient with classical phenylketonuria (PKU). It is a single
      base transition of G to A at the last base in intron 4 of the gene, which
      abolishes the 3'-acceptor site of the intron. Population screening indicates that
      this mutation constitutes about 8% of all PKU chromosomes in Chinese but is
      absent in Japanese and Caucasian PKU patients. It is prevalent in southern China
      but rare in northern China, providing additional evidence that there were
      multiple founding populations of PKU in east Asia.

PMID- 1998346
TI  - Biostatistics in paternity testing using genetic systems with linkage
      disequilibrium.

PMID- 1998347
TI  - The good news: healthcare jobs keep booming.

PMID- 1998348
TI  - This war I can't knit socks.

PMID- 1998349
TI  - A flower in the emergency department.

PMID- 1998350
TI  - Serving justice: how to give a deposition.

PMID- 1998351
TI  - Healing with thin-film dressings.

PMID- 1998352
TI  - Arrhythmia mimics.

PMID- 1998353
TI  - How to care for the diabetic foot.

PMID- 1998354
TI  - White clot syndrome: when heparin goes haywire.

PMID- 1998355
TI  - Mary & Leroy.

PMID- 1998356
TI  - How to ask research questions in clinical practice.

PMID- 1998357
TI  - Nursing needs its own wall of protest.

PMID- 1998358
TI  - Midwest jobfocus. Transplant care: giving patients a new lease on life.

PMID- 1998359
TI  - Chicago jobfocus. A forceful health care community.

PMID- 1998361
TI  - Occupational Therapy. Buyer's Guide 1991.

PMID- 1998360
TI  - Continuous SC morphine for cancer pain.

PMID- 1998362
TI  - Evaluation and management of melanonychia striata in a patient receiving
      phototherapy.

PMID- 1998363
TI  - Avian aesthetics. Brightness is for the birds.
AB  - Progress in clinical dermatology is derived from new diagnostic and therapeutic
      approaches and requires increased understanding of the cellular and
      macromolecular basis of physiology and pathophysiology. Researchers are excited
      and animated by their experiments and data, yet the research literature
      frequently fails to convey this immediacy. Why? In part, the convention and form
      of scientific journals and the eschewing of speculation make the literature
      inaccessible to the nonscientist. This section of the ARCHIVES will select
      broadly from the research literature relevant to dermatology and will attempt to
      integrate what is new in the research laboratory with the physicians' knowledge.
      Readers' comments are solicited.

PMID- 1998364
TI  - Outcomes of pregnancies among women and partners of men with a history of
      exposure to methoxsalen photochemotherapy (PUVA) for the treatment of psoriasis.
AB  - Because oral methoxsalen and UV-A radiation (PUVA) therapy is mutagenic, concern
      exists about the potential for teratogenic effects resulting from the use of this
      therapy at the time of conception and during pregnancy. After 12.8 years of
      prospective study, we documented the pregnancy outcomes among 1380 patients (892
      men and 488 women) who received PUVA treatments. Ninety-four men reported 167
      pregnancies in their partners, and 93 women reported 159 pregnancies. For 34% of
      pregnancies among partners of male patients, the man received PUVA therapy near
      the time of conception. Nineteen percent of female patients reported exposure to
      PUVA at the time of conception or during pregnancy. Induced and spontaneous
      abortions were reported as the outcome of pregnancy more often by female than by
      male patients (12% vs 30%). Two congenital malformations and two stillbirths
      occurred, an incidence not significantly different from that expected for the
      general population. Although the power of our study to detect an increase in the
      risk of specific defects is limited, our data show no evidence to suggest that
      PUVA is a potent teratogen. Still, because PUVA is mutagenic, we believe it
      prudent for patients to avoid PUVA treatment during pregnancy whenever practical.

PMID- 1998365
TI  - Efficiency of opaque photoprotective agents in the visible light range.
AB  - "Opaque" physical sunscreens are important for photoprotection of individuals
      with visible light and UV-A photosensitivity such as those with porphyria, drug
      photoallergy, and polymorphous light eruption. Diffuse spectral transmittance of
      various thicknesses of opaque sunscreen formulations were measured from 350- to
      800-nm range using a spectrophotometer equipped with an integrating sphere.
      Transmission through 20% zinc oxide paste was high and decreased minimally
      despite large increases in the sunscreen layer thickness. Adding a visible light
      absorber such as iron oxide to scattering sunscreens, however, substantially
      lowered transmittance below that predicted by the product of the transmittances
      for each component alone. Opaque sunscreens protected against hematoporphyrin
      derivative photosensitization of albino guinea pig skin; these results were
      quantitatively consistent with the in vitro findings. Poor photoprotection
      against visible light is obtained with white paste sunscreens, even if thick
      layers are applied. The addition of pigments to such sunscreens, however, greatly
      enhances photoprotection and cosmetic acceptability.

PMID- 1998367
TI  - Nasal midline masses in infants and children. Dermoids, encephaloceles, and
      gliomas.
AB  - Nasal dermoids, gliomas, and encephaloceles are uncommon congenital lesions that
      result from aberrant embryologic development. We have treated 46 children with
      these nasal lesions. In view of the potential intracranial connection, patients
      are at risk for intracranial infection, and early surgical correction is thus
      imperative. Neuroimaging studies may help to predict intracranial involvement.

PMID- 1998366
TI  - A community study of delay in presenting with signs of melanoma to medical
      practitioners.
AB  - In the absence of more effective treatment for advanced tumors, early diagnosis
      and treatment of localized tumors is the most effective way of reducing the
      burden of illness associated with melanoma. This study examined the following
      factors: prevalence of signs of melanoma (a mole changing in size, shape,
      appearance, or color, itching or tingling, bleeding or weeping, becoming raised)
      in 1344 individuals in a randomly selected sample of 1075 households; the length
      of delay in seeking medical advice; the factors associated with either going to a
      medical practitioner or not going/delaying; and the actions of the medical
      practitioners when first presented with these signs. The results indicate that a
      large proportion of the sample (11.9%, n = 156) had observed signs of melanoma in
      the previous 12 months. Of the sample reporting signs that had first appeared in
      the previous 5 years, only 32% sought medical advice about the signs within the
      recommended period. Of the sample either not seeking advice at all or delaying,
      49% reported that they thought the sign "wasn't serious/would clear up."
      Furthermore, 30% of the sample either did not known or underrated the importance
      of early detection and treatment of lesions. These results indicate that there is
      a deficit in the knowledge of the general public about the signs of melanoma, the
      severity of the disease, and the possible risks associated with delay.

PMID- 1998368
TI  - Epidermolysis bullosa acquisita and associated symptomatic esophageal webs.
AB  - Epidermolysis bullosa acquisita (EBA) is a well-characterized, subepidermal
      blistering disorder associated with autoimmunity to type VII collagen, which is
      the collagen localized to anchoring fibrils within the dermoepidermal junction of
      skin. Although the full clinical spectrum of EBA is still being defined, it is
      known that the clinical features of EBA may be reminiscent of hereditary
      dystrophic epidermolysis bullosa, a scarring blistering disease of children that
      is commonly associated with esophageal stenosis. We describe a patient with EBA
      who had both an acral-predominant mechanobullous disease akin to dystrophic
      epidermolysis bullosa and an inflammatory, widespread bullous eruption
      reminiscent of bullous pemphigoid in association with esophageal webs and
      dysphagia. Although esophageal involvement is common in dystrophic epidermolysis
      bullosa, a review of the literature shows that this is the first bonafide case of
      EBA with symptomatic esophageal disease.

PMID- 1998369
TI  - Childhood bullous pemphigoid. Clinical and immunologic features, treatment, and
      prognosis.
AB  - A 2 1/2-month-old female infant presented with multiple tense bullae on the hands
      and feet. Analysis of biopsy specimens confirmed our clinical impression of
      childhood bullous pemphigoid. Confirmatory data included type IV collagen mapping
      of the basement membrane zone, a readily available technique that helps
      distinguish childhood bullous pemphigoid from childhood epidermolysis bullosa
      acquisita. To our knowledge, our patient is the youngest described with childhood
      bullous pemphigoid, and we use this opportunity to review the literature and
      examine the clinical and immunologic features, treatment, and prognosis of this
      rare childhood immunobullous disorder.

PMID- 1998370
TI  - Coexistence of pemphigus foliaceus and bullous pemphigoid. Demonstration of
      autoantibodies that bind to both the pemphigus foliaceus antigen complex and the
      bullous pemphigoid antigen.
AB  - Pemphigus and bullous pemphigoid are autoimmune blistering diseases of the skin
      characterized by circulating autoantibodies directed against the keratinocyte
      cell surface and the epidermal basement membrane zone, respectively. The
      coexistence of pemphigus and bullous pemphigoid is very uncommon. We describe a
      patient with pemphigus foliaceus who later developed bullous pemphigoid and show,
      by means of immunoprecipitation studies utilizing both cultured keratinocytes and
      suction blister epidermis, that our patient had circulating autoantibodies
      directed against both the pemphigus foliaceus antigen complex and the bullous
      pemphigoid antigen. This report is the first to demonstrate the coexistence of
      pemphigus foliaceus and bullous pemphigoid at the molecular level.

PMID- 1998371
TI  - Acquired epidermolysis bullosa with the clinical feature of Brunsting-Perry
      cicatricial bullous pemphigoid.
AB  - A 56-year-old woman with the typical clinical feature of cicatricial bullous
      pemphigoid of the Brunsting-Perry type was studied. Histologic examination of a
      lesion skin biopsy specimen demonstrated a subepidermal blister. Direct
      immunofluorescence microscopy revealed linear deposits of IgG, IgM, and C3
      located on both the roof and the floor of the blister. Immunofluorescence antigen
      mapping using cryostat sections of a spontaneous blister and antisera against
      defined basement membrane components localized the bullous pemphigoid antigen and
      type IV collagen in the roof of the blister. This dermal type of blister
      formation was confirmed by electron microscopy, which showed the cleavage level
      below the lamina densa. In direct immunoelectron microscopy, granular deposits of
      C3 and IgG were found attached to and just beneath the lamina densa in a pattern
      identical to the distribution of anchoring fibrils. These findings are diagnostic
      of acquired epidermolysis bullosa, a blistering disease that has much more
      clinical heterogeneity than previously suggested.

PMID- 1998372
TI  - Teratogens and the dermatologist. New knowledge, responsibilities, and
      opportunities.

PMID- 1998373
TI  - Reticular erythema of the lower back. Erythema ab igne.

PMID- 1998374
TI  - Ulcerated papules, plaques, and nodules of the scalp and face. Cutaneous
      Hodgkin's disease.

PMID- 1998375
TI  - Tumorous nodules on the lower extremities. Systemic mastocytosis.

PMID- 1998376
TI  - An old lady with scarring alopecia and an ulcerated sole. Ulcerative lichen
      planus.

PMID- 1998377
TI  - Lentigo maligna and Mohs.

PMID- 1998378
TI  - Mohs surgery: qualifications and certification.

PMID- 1998379
TI  - Multiple eccrine hidrocystomas: a nonsurgical treatment.

PMID- 1998380
TI  - Foreign-body granuloma on the forehead: reaction to bindi.

PMID- 1998381
TI  - Moth cocoon dermatitis.

PMID- 1998382
TI  - Erectile dysfunction in etretinate treatment.

PMID- 1998383
TI  - Psoriasis, cyclosporine, and pregnancy.

PMID- 1998384
TI  - Diagnostic value of synovial fluid microscopy: a reassessment and
      rationalisation.
AB  - This study is in two parts. In the first synovial fluid from 1892 patients with
      14 different arthropathies was examined microscopically. Crystals of different
      types were identified and the disease distribution of these and various cell
      types, including several not previously reported in synovial fluid, have been
      described. These features have been used to derive a series of microscopic
      diagnostic criteria for each arthropathy. The criteria have been used in the
      second part of the study to examine synovial fluids from 200 patients without
      knowledge of any clinical diagnosis. Cytological and clinical diagnoses were
      compared at the end of the study. Matching diagnoses were made in 71 (35.5%) and
      a short list of differential diagnoses (based on cytological criteria), which
      included the clinical diagnosis, was made in a further 43 (21.5%). Of the rest,
      63 (31.5%) were correctly described as inflammatory or non-inflammatory and in
      five (2.5%) no diagnosis could be made. Only in seven cases (3.5%) was an
      inaccurate (false positive) cytological diagnosis made. The results indicate that
      synovial fluid microscopy is a potentially more important diagnostic screening
      test in rheumatological and orthopaedic practice than it would at first appear
      from published reports.

PMID- 1998385
TI  - Sporotrichal arthritis.
AB  - Sporotrichal arthritis is a rare disease entity. Diagnosis is often difficult and
      delayed. Presentation may be either monoarticular or polyarticular. A case of
      polyarticular sporotrichal arthritis which exemplifies these problems is
      reported.

PMID- 1998386
TI  - Behcet's disease in a patient with immunodeficiency virus infection.
AB  - A patient with human immunodeficiency virus (HIV) infection who developed
      Behcet's disease is described. As various vasculitis syndromes have been
      encountered recently in association with HIV infection it is suggested that
      Behcet's disease may be related to the HIV infection in this patient.

PMID- 1998387
TI  - Spondylodiscitis and pseudarthrosis in a patient with enteropathic
      spondyloarthropathy.

PMID- 1998388
TI  - Role of cytological analysis of synovial fluid in diagnosis and research.

PMID- 1998389
TI  - Elastase-alpha 1 proteinase inhibitor assay.

PMID- 1998390
TI  - Seronegative rheumatoid arthritis associated with AIDS.

PMID- 1998391
TI  - A case of chronic Lyme arthritis in England.

PMID- 1998392
TI  - Pregnancy and its effect on the risk of developing rheumatoid arthritis.

PMID- 1998393
TI  - Oral contraception and its possible protection against rheumatoid arthritis.

PMID- 1998394
TI  - In vivo studies of cartilage regeneration after damage induced by
      catabolin/interleukin-1.
AB  - The response of the rabbit knee joint to a brief episode of cytokine induced
      damage is described. After three intra-articular injections of
      catabolin/interleukin-1 all joint cartilages showed an immediate extensive loss
      of proteoglycan (glycosaminoglycan), which was gradually replaced over three to
      four weeks. Glycosaminoglycan biosynthesis (measured by 35SO4 uptake) was
      initially depressed, but at one week had almost doubled its rate as compared with
      the normal side. This increased synthetic activity was further maintained
      throughout the duration of the experiment (28 days), though the rate gradually
      fell. Histological cartilage metachromasia to toluidine blue mirrored the
      glycosaminoglycan changes. No disturbance of the articular cartilage collagen
      network was found. It is considered, therefore, that during treatment for
      arthritis the indigenous chondrocyte must continue to be capable of carrying out
      regenerative matrix repair and that antiarthritic agents should first be screened
      for interference with that process.

PMID- 1998395
TI  - Chain breaking antioxidant status in rheumatoid arthritis: clinical and
      laboratory correlates.
AB  - The ability of fresh sera to resist attack by peroxyl radicals (TRAP) was found
      to be significantly lower in 20 patients with rheumatoid arthritis (RA) than in
      20 healthy controls, consistent with the existence of a redox stress in RA
      imposed by inflammation. TRAP values in RA varied inversely with a combination of
      visual analogue pain scale, duration of early morning stiffness, grip strength,
      and articular index (reflecting inflammatory activity) using multiple linear
      regression analysis. The concentration of the antioxidant vitamin ascorbic acid
      was lower in RA plasma and the oxidation-reduction equilibrium of ascorbic acid
      was disturbed, giving further support to the existence of a redox stress. The
      major determinant of TRAP in vitro was found to be serum uric acid in RA and
      serum vitamin E in controls. Serum urate concentration in RA correlated inversely
      with oxidative changes in serum albumin and IgG. It is suggested that serum urate
      might have an antioxidant role under certain conditions by limiting free radical
      induced oxidative changes to protein during inflammation.

PMID- 1998396
TI  - Bacterial antigens in synovial biopsy specimens in yersinia triggered reactive
      arthritis.
AB  - Non-viable structures of Yersinia enterocolitica O:3 were shown at the site of
      inflammation within mononuclear cells in the synovial membrane of eight out of 10
      patients with yersinia triggered reactive arthritis. An avidin-biotin-peroxidase
      complex method, with a rabbit antiserum specific for Y enterocolitica O:3, was
      used to visualise yersinia structures. All 13 control samples were negative
      except for one with non-specific mast cell staining. The findings emphasise the
      significance of foreign material in the initiation of synovitis in reactive
      arthritis.

PMID- 1998398
TI  - Mortality from scleroderma in England and Wales 1968-1985.
AB  - Mortality data for scleroderma derived from death certificates from England and
      Wales for the years 1968-1985 were analysed. The overall crude mortalities were
      0.9 and 3.8 per million per year in men and women respectively, which are similar
      to comparable data from the United States. There has been a small but
      statistically significant increase in mortality of 3% a year over this period,
      possibly reflecting an underlying increasing trend in incidence. Such analyses
      are subject to the limitation of the accuracy of death certificates, but in a
      disease as rare as scleroderma the death rates provide useful data on the trends
      in occurrence and death from this disease.

PMID- 1998397
TI  - Intestinal permeability in patients with yersinia triggered reactive arthritis.
AB  - The passive intestinal permeability of patients with yersinia triggered reactive
      arthritis was studied using different sized polyethylene glycols (PEGs) contained
      in a mixture of PEG 400 and PEG 1000. The investigation was carried out at least
      one year after the onset of yersinia infection, and patients had neither acute
      gastrointestinal nor joint symptoms. The control groups included patients with
      uncomplicated yersiniosis as well as healthy subjects who were either HLA-B27
      positive or negative. An altered intestinal barrier function to PEG molecules was
      detected in patients with a history of yersinia infection compared with healthy
      controls. No significant differences in the permeability were found between
      patients with or without reactive arthritis, nor was there any association of
      increased permeability with HLA-B27. The passive permeability of the intestinal
      mucosa to the larger molecules was increased for an unexpectedly long time after
      the acute yersinia infection, probably contributing to the perpetuation of joint
      symptoms in subjects susceptible to a chronic joint disease.

PMID- 1998399
TI  - Types of atrophic gastritis in patients with primary Sjogren's syndrome.
AB  - Histological examination of the gastric mucosa was performed in 44 patients with
      primary Sjogren's syndrome with extraglandular symptoms (mean age 51.9, range 22
      76). Biopsy specimens were taken from each of three separate regions: the antrum,
      the corpus, and the transitional zone between the antrum and the corpus. The
      incidence of chronic atrophic gastritis was considerably higher in patients with
      Sjogren's syndrome than in the controls. In the young patients with Sjogren's
      syndrome atrophic lesions were more common both in the antrum and in the corpus
      than in the control group. In middle aged patients, however, only the antrum, and
      in the elderly only the corpus, was much more commonly affected than in the
      controls. All three types of chronic atrophic gastritis occurred in patients with
      Sjogren's syndrome. Decreased gastric acid secretion was associated mainly with
      atrophic gastritis of types A and AB, whereas hypergastrinaemia occurred almost
      exclusively in gastritis of type A.

PMID- 1998400
TI  - The spectrum of portal vein thrombosis in liver transplantation.
AB  - Thrombosis of the portal vein with or without patency of its tributaries used to
      be a contraindication to orthotopic liver transplantation (OLTX) until quite
      recently. Rapid progress in the surgical technique of OLTX in the last few years
      has demonstrated that most patients with portal vein thrombosis can be safely and
      successfully transplanted. Presented here is a series of 34 patients with portal
      vein thrombosis transplanted at the University of Pittsburgh since 1984. The
      various techniques used to treat various forms of thrombosis are described. The
      survival rate for this series was 67.6% (23 of 34 patients). Survival was best
      for patients who underwent phlebothrombectomy or placement of a jump graft from
      the superior mesenteric vein. The survival rate also correlated with the amount
      of blood required for transfusion during surgery. Overall it is concluded that a
      vast majority of the patients with thrombosis of the portal system can be
      technically transplanted and that their survival rate is comparable to that of
      patients with patent portal vein.

PMID- 1998401
TI  - Severe gastrointestinal hemorrhage in Crohn's disease.
AB  - Twenty-one of fifteen hundred twenty-six patients with Crohn's disease (CD)
      treated at The Mount Sinai Hospital between 1960 and 1986 developed severe
      gastrointestinal hemorrhage. There were 26 separate episodes of severe
      hemorrhage: 17 patients bled only once, three bled twice and one bled three
      times. The frequency of bleeding was significantly higher among patients with
      colonic involvement (17 of 929; 1.9%) than among those with small bowel disease
      alone (4 of 597; 0.7%) (p less than 0.001). Twelve patients required surgery on
      13 occasions, which involved colon resection in all but one case. Eleven of these
      patients underwent surgery during their first hemorrhagic episodes, and 1 of 11
      had a second operation for recurrent bleeding; the 12th patient, whose first
      hemorrhage had been treated medically, had surgery during a repeated episode of
      hemorrhage. The precise bleeding points could be located in only 2 of the 26
      bleeding episodes, both at the ileocecal area. Three patients died, of whom two
      had not undergone surgery when they had bled a few weeks earlier. Primary
      bleeding episodes subsided without surgery in 10 of 21 cases, but 3 of these 10
      patients (30%) rebled massively. By contrast primary excisional surgery was
      followed by recurrent hemorrhage in only 1 of 11 cases (9%). These differences in
      mortality and in recurrent bleeding rates, although not statistically
      significant, seem to favor removal of diseased bowel at the time of the first
      episode of massive hemorrhage.

PMID- 1998402
TI  - Indications for computed tomography in children with blunt abdominal trauma.
AB  - This investigation was undertaken to identify clinical variables, alone or in
      combination, that could be used to assign children to high- and low-risk
      categories for intra-abdominal injury following blunt trauma. Six hundred
      consecutive children who were examined with computed tomography (CT) following
      blunt trauma were enrolled. Complete data sets were available on 375 children.
      Stepwise logistic regression was used to identify predictor variables for the
      presence of abdominal injury. There were 174 children with abdominal injury
      detected by CT. Of these, 95 were classified as having significant injury.
      Indicators associated with significantly higher risk of abdominal injury included
      the following: more than three clinical indications given (odds likelihood ratio
      [OLR] = 4.60, 95% confidence interval [95% Cl] = 2.29, 9.21, p less than 0.001);
      gross hematuria (OLR = 5.80, 95% Cl = 2.51, 13.4, p less than 0.001); lap belt
      injury (OLR = 12.2, 95% Cl = 2.22, 66.8, p less than 0.01); assault or abuse as
      the mechanism of injury (OLR = 5.08, 95% Cl = 1.07, 24.2, p less than 0.05);
      abdominal tenderness (OLR = 2.73, 95% Cl = 1.296, 5.82, p less than 0.01); and
      Trauma Score less than or equal to 12 (OLR = 2.27, 95% Cl = 1.006, 5.13, p less
      than 0.01). No child with asymptomatic hematuria (n = 56), regardless of grade or
      neurologic impairment in the absence of abdominal findings (n = 15), had an
      abnormal CT examination. These data are useful as an adjunct to clinical judgment
      in triage when the availability of CT equipment is limited or there are competing
      extra-abdominal injuries.

PMID- 1998403
TI  - Human liver regeneration after major hepatectomy. A study of liver volume by
      computed tomography.
AB  - Regeneration of the remnant liver after major hepatectomy in humans was studied
      by computed axial tomography (CT) in 12 noncirrhotic and five cirrhotic patients.
      Liver volumes were measured by abdominal CT 3 days, 10 days, 3 months, 6 months,
      1 year, and 1.5 years after resection. Of the 17 patients, liver remnant volume
      was increased in 21.2% +/- 6.7% and 30.6% +/- 12.7% at 3 months and 6 months
      after resection, respectively. Noncirrhotic livers were 28.4% +/- 9.5% and 48.4%
      +/- 17.8% larger at 3 and 6 months. For cirrhotic livers, the increase was 8.5%
      +/- 3.6% and 12.9% +/- 4.5%. In five patients with right hepatectomy (65%
      resection), the liver remnant volumes were increased 38.4% +/- 11.7%, 48.0% +/-
      16.2% and 95.1% +/- 4.5% at 3 months, 6 months, and 1 year after resection,
      respectively. In seven patients with right partial hepatectomy (30% to 35%
      resection), the percentages were 7.4% +/- 3.2%, 21.8% +/- 8.4%, and 63.9% +/-
      18.3% and in five patients with left lateral segmentectomy (15% resection), they
      were 15.6% +/- 8.2%, 27.8% +/- 12.2%, and 33.0% +/- 14.5% 3 months, 6 months, and
      1 year after resections, respectively. Noncirrhotic livers showed better
      regeneration than cirrhotic livers. Complete regeneration took about 1 year. The
      noncirrhotic liver that underwent right lobectomy also needed 1 year to double
      its postresection volume.

PMID- 1998404
TI  - A valved hepatic portoduodenal intestinal conduit for biliary atresia.
AB  - Forty-six consecutive patients with biliary atresia were operated on at our
      institution during the 11-year period between 1978 and 1989. Their ages at
      operation ranged from 18 to 153 days (mean, 59 days). After dissecting the porta
      hepatis structures by Kasai operation, a biliointestinal anastomosis was
      constructed with a valved hepatic portoduodenal intestinal conduit in all cases.
      The intestinal valve is an intussuscepted muscular valve. Valvular function was
      examined radiologically. The upper gastrointestinal series demonstrated no reflux
      of contrast material into the conduit proximal to the valve and liver
      scintigraphy demonstrated that radioactive isotope drained readily into the
      duodenum through the valve. Thirty-nine of the forty-six patients (85%) had bile
      drainage after initial operation. At present 30 patients (65%) are alive without
      jaundice, 6 (13%) are alive with jaundice, and 10 (22%) are dead. The 5-year
      jaundice-free survival rate was 64%. Cholangitis occurred in 9 of 39 patients
      (23%) who had obtained apparent bile drainage: 5 had tractable cholangitis and 4
      had refractory cholangitis. Reoperation restored bile flow in 2 of 8 patients who
      abruptly ceased to have bile drainage without cholangitis. In conclusion, with a
      valved hepatic portoduodenal intestinal conduit, the incidence of cholangitis was
      decreased, its medical control became easier, and the survival rate was improved.

PMID- 1998405
TI  - Defining the role of subtotal colectomy in the treatment of carcinoma of the
      colon.
AB  - Seventy-two patients with colon cancer were treated by primary subtotal
      colectomy, including 23 patients with acute and subacute left colon obstruction.
      There were two operative deaths and no cases of disabling diarrhea. One death
      occurred in the group with colon obstruction. Other indications for subtotal
      colectomy included multiple polyps associated with the primary tumor (32),
      synchronous carcinomas (15), a previous transverse colostomy for obstruction (8),
      associated severe sigmoid diverticular disease (2), age less than 50 years with a
      positive family history (3), adherence of the sigmoid loop to a cecal tumor (2),
      and metachronous carcinoma (2). There were multiple indications in several
      patients. Subtotal colectomy has a defined role in a wide variety of clinical
      settings associated with colon cancer, including management of obstruction of the
      left and sigmoid colon, particularly if the proximal colon cannot be evaluated
      before operation by colonoscopy or barium enema. Segmental or regional colonic
      resections are appropriate if the entire colon can be evaluated before operation
      and no associated neoplasms are revealed.

PMID- 1998407
TI  - Elevated plasma endothelin-1 concentrations are associated with the severity of
      illness in patients with sepsis.
AB  - Plasma immunoreactive endothelin-1 concentrations were determined by
      radioimmunoassay in 11 septic patients during the first 24 hours after the
      development of the sepsis syndrome in 15 nonseptic postoperative patients studied
      24 hours after open heart surgery and in 14 healthy volunteers. Mean endothelin-1
      plasma concentrations were significantly (p less than 0.001) increased in septic
      patients (19.9 +/- 2.2 pg/mL, mean +/- standard error) compared to concentrations
      found in postoperative cardiac patients (11.9 +/- 0.7 pg/mL) or in healthy
      volunteers (6.1 +/- 0.3 pg/mL). In septic patients elevated plasma concentrations
      of endothelin-1 were inversely correlated with cardiac index (r = -0.80, p less
      than 0.005) and positively correlated the severity of illness as documented by
      APACHE II score (r = 0.74, p less than 0.01) and plasma creatinine levels (r =
      0.80, p less than 0.005). No such correlations were found in postoperative
      cardiac patients. These results indicate that endothelin-1 concentrations are
      correlated with the severity of illness and depression of cardiac output in
      patients with sepsis.

PMID- 1998406
TI  - The peritoneal environment during infection. The effect of monomicrobial and
      polymicrobial bacteria on pO2 and pH.
AB  - Intraperitoneal (IP) abscesses frequently are composed of aerobes and anaerobes,
      and, in experimental models, a particulate adjuvant. The environmental changes
      effected by these components, either singularly or in combination, have not been
      well defined. The IP pO2, pH, and recoverable bacteria from the peritoneum of
      rats were quantified over 6 hours during simple aerobic and anaerobic infections
      and during mixed peritonitis with and without a sterile feces-barium sulfate
      adjuvant (SFA). Fourteen groups were studied, receiving intraperitoneally, at
      time of oxygen probe placement, 1 mL normal saline (control), Escherichia coli
      (EC), Bacteroides fragilis (BF), SFA alone, or a mixture of EC and BF, EC and
      SFA, BF and SFA, or EC, BF, and SFA. Control animals exhibited a stable IP pO2
      and pH during 6 hours. In monomicrobial EC peritonitis, inocula well below the
      LD50 produced an increased IP pO2 and reduced arterial-peritoneal gradient (APG),
      with a stable IP pH. By 6 hours lethal doses of EC produced a dramatic decline in
      IP pO2, with no change in arterial pO2 as well as acidic IP and arterial pHs.
      Simple BF peritonitis caused no or minor elevations in IP and arterial pO2 with
      no change in pH. During mixed infections a significant decline in the IP pO2 and
      pH at 6 hours in those groups infected with both SFA and EC of a moderate,
      normally sublethal inoculation was observed, while arterial pO2 was unchanged and
      arterial pH was decreased only slightly. Concomitantly there was a significant
      increased number of aerobic bacteria in those groups with SFA as adjuvant
      compared to similar inocula without SFA. This study demonstrates the complex
      interactions of bacteria, sterile particulate adjuvant (SFA), and the host
      peritoneum. It suggests that the combination of SFA and aerobic bacteria alter
      the peritoneal environment to one permitting anaerobic growth and promoting
      abscess formation.

PMID- 1998408
TI  - Blockade of prostaglandin production increases cachectin synthesis and prevents
      depression of macrophage functions after hemorrhagic shock.
AB  - Although hemorrhage severely depresses macrophage functions, it is not known
      whether the increased TNF-alpha or PGE2 production is responsible for it. To
      study this C3H/HeN mice were bled to mean blood pressure of 35 mmHg for 60
      minutes, resuscitated, and treated with either ibuprofen (1.0 mg/kg body weight)
      or vehicle (saline). Hemorrhage increased plasma prostaglandin E2 (PGE2) levels
      by 151.7% +/- 40.0% (p less than 0.05) and significantly decreased peritoneal
      macrophage (pM phi) antigen presentation (AP) by 60.5% +/- 7.3%, Ia expression by
      52.3% +/- 7.6%, and interleukin-1 (IL-1) synthesis by 60.5% +/- 12.3% compared to
      shams. However ibuprofen treatment reduced PGE2 plasma levels by 61.3% +/- 12.1%
      and significantly increased AP (+237.0% +/- 95.3%), Ia expression (+72.8% +/-
      27.5%), IL-1 synthesis (+235.7% +/- 134.7%), and cachectin synthesis (+485.8% +/-
      209.0%) compared to vehicle-treated animals. These results indicate that
      prostaglandins but not cachectin are involved in the suppression of pM phi
      functions following hemorrhage because blockade of prostaglandin synthesis
      improved depressed macrophage functions despite enhanced cachectin synthesis.

PMID- 1998409
TI  - Simultaneous bilateral hernia repair. A case against conventional wisdom.
AB  - The timing of bilateral hernia repair remains controversial. Because of reported
      high recurrence rates after simultaneous bilateral repair, staged procedures have
      been suggested. This study determined recurrence and complication rates of
      unilateral versus simultaneous bilateral repair. Of 659 patients undergoing
      hernia repair between 1974 and 1980, 333 underwent unilateral repair and 329 had
      simultaneous bilateral repair. More than 90% of patients were followed until
      death or a minimum of 60 months (median, 104 months). Perioperative complications
      were associated with 18% of repairs. More morbidity occurred in the bilateral
      group. However complication rates for specific events were not significantly
      different, except for urinary retention, which occurred in 20 patients (6.1%) of
      the unilateral group and 49 (15%) of the bilateral group (p less than 0.001).
      Overall 25 recurrences occurred in the unilateral group and 31 in the bilateral
      group. Recurrence rates at 5 and 9 years were, respectively, 4.8% and 8.8% in the
      unilateral group and 5.0% and 9.1% in the bilateral group (p = 0.861). These data
      suggest that simultaneous bilateral inguinal herniorrhaphy does not result in
      increased rates of most postoperative complications or recurrence when compared
      with unilateral repair.

PMID- 1998410
TI  - Preparation, trust, and responsibility.

PMID- 1998411
TI  - Valve re-replacement in the asymptomatic patient.

PMID- 1998412
TI  - Magnesium ion is beneficial in hypothermic crystalloid cardioplegia.
AB  - The role of magnesium ion and its relation to the calcium concentration of
      cardioplegic solutions was reexamined in this study. Isolated rat hearts were
      used with an oxygenated modified Krebs-Henseleit bicarbonate buffer as perfusion
      medium. The hearts were arrested for 20 minutes at 37 degrees C or 90 minutes at
      24 degrees C. Treatment groups received one dose of nine possible cardioplegic
      solutions containing magnesium (0, 1.2, or 15 mmol/L) and calcium (0.05, 1.5, or
      4.5 mmol/L). Ninety-six percent of the 75 magnesium-treated hearts recovered,
      regardless of the calcium concentration, in contrast to a 52% recovery rate in
      the 69 hearts that did not receive magnesium. The addition of 15 mmol/L Mg2+ to a
      cardioplegic solution containing no magnesium but 0.05 mmol/L Ca2+ significantly
      increased (p less than 0.01) the percent recovery of the following parameters of
      cardiac function: systolic pressure, 74% to 93% (37 degrees C), 64% to 98% (24
      degrees C); cardiac output, 76% to 101% (37 degrees C), 71% to 102% (24 degrees
      C); stroke work, 64% to 104% (37 degrees C), 52% to 99% (24 degrees C); and
      adenosine triphosphate level, 75% to 83% (37 degrees C), 58% to 90% (24 degrees
      C). There were significant reductions (p less than 0.03) in percent recovery (37
      degrees C and 24 degrees C) of cardiac output, stroke work, and adenosine
      triphosphate level in the groups that contained 0 or 15 mmol/L Mg2+ as the
      calcium concentration was increased from 0.05 to 4.5 mmol/L.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1998413
TI  - Bronchoalveolar carcinoma: factors affecting survival.
AB  - One hundred thirty-four consecutive patients (65 men and 69 women) underwent
      pulmonary resection for bronchoalveolar carcinoma. Mean age was 65 years.
      Lobectomy was done in 100 patients, pneumonectomy in 10, segmentectomy in 5, and
      wedge excision in 19. Only 10 patients had lymph node metastases (7.5%). The
      neoplasm was solitary in 111 patients (82.8%); 97 were in stage I, 4 were in
      stage II, 9 were in stage IIIa, and 1 was in stage IIIb. There were two operative
      deaths (1.5%). Thirty-nine complications occurred in 31 patients. Median follow
      up was 5.1 years. Recurrent bronchoalveolar carcinoma developed in 45 patients.
      Five- and 10-year survival for patients in stage I was 75.2% and 62.0%,
      respectively. Survival for patients with T1 N0 M0 neoplasms was identical to
      expected survival and was 90.5% at 5 years, as compared with 55.4% for patients
      with T2 N0 M0 disease, only 35.9% for patients with multiple bilateral disease,
      and 0.0% for patients with bilateral disease (p less than 0.0001). Other
      significant factors adversely affecting survival included the presence of signs
      and symptoms, diffuse malignant invasion, mucin-producing tumors, and the
      histological absence of scar. We conclude that bronchoalveolar carcinoma has a
      unique natural history that is more influenced by local neoplastic processes than
      by lymph node metastases. Early aggressive pulmonary resection is safe and offers
      the potential for cure. The presence of bilateral cancer, however, is ominous.

PMID- 1998414
TI  - Primary cysts and tumors of the mediastinum.
AB  - A retrospective analysis was performed on 230 patients with primary cysts and
      tumors of the mediastinum seen at our institution from January 1944 to April
      1989. We divided these patients into two groups. Group 1 was seen before 1970 and
      group 2 was seen from January 1970 to April 1989. There was a significant
      increase in the prevalence of malignancy in group 2 (47.2% versus 17.1%; p less
      than 0.0001) due to an increase in the number of lymphomas (22.6% versus 3.5%; p
      less than 0.001) and malignant neurogenic tumors (6.8% versus 1.1%; p = 0.0528).
      There was a significant increase in the number of malignant tumors in the
      anterior (59.5% versus 30.9%; p = 0.0022) and paravertebral (28.5% versus 2.8%; p
      = 0.0027) compartments in group 2. More patients with these tumors were
      symptomatic in group 2 (63.6% versus 5%; p = 0.0422). There was an increase of
      ancillary diagnostic studies performed to evaluate these tumors (76.0% versus
      34.5%; p = 0.0422). Logistic regression analysis identified date of presentation
      (p less than 0.005), symptoms (p less than 0.01), size (p less than 0.005), and
      the anterior mediastinal compartment (p less than 0.005) as preoperative
      predictors of malignancy. The surgical approach to these tumors included more
      median sternotomy (30.1% versus 10.7%; p = 0.0008), anterior mediastinotomy, and
      cervical mediastinoscopy in group 2 (1.1% versus 17.5%; p = 0.0002). Long-term
      results support surgical resection in benign lesions and an aggressive
      multimodality approach to malignant lesions.

PMID- 1998415
TI  - Site of action of continuous extrapleural intercostal nerve block.
AB  - Continuous extrapleural intercostal nerve block has been shown in a randomized,
      controlled study to be effective in reducing postoperative pain after thoracotomy
      and in restoring pulmonary mechanics. To assess the extent of spread of
      bupivacaine infused through an extrapleurally placed cannula inserted at
      thoracotomy, iohexol (Omnipaque) was infused at 5 days postoperatively in 5
      patients and computed tomography performed. The contrast medium was confined to
      the paravertebral space covering on average six intercostal spaces. This study
      demonstrated that anatomically, the site of action of the bupivacaine infused
      through an extrapleural cannula was primarily in the paravertebral space.

PMID- 1998416
TI  - Fibrous skeleton and ventricular outflow tracts in double-outlet right ventricle.
AB  - Twenty-four hearts in which both great arteries arose from the right ventricle
      were studied to establish variations present within the fibrous skeleton and
      infundibular morphologies. Variations were also noted in the location of the
      ventricular septal defect and measurements were obtained of the outlet septum and
      the circumferences of the arterial valves. Completely muscular subarterial
      infundibulums were present in only 9 (37.5%) of the hearts, with varying degrees
      of fibrous continuity between the leaflets of the arterial and atrioventricular
      valves in the remainder. The aorta was rightward and posterior in 12 (50%) of the
      hearts, and subaortic and subpulmonary ventricular septal defects were present in
      equal numbers in this group. No subaortic defects were present when the aorta was
      side-by-side and right-sided. No subpulmonary defects were present in hearts with
      a posterior aorta. The mean ratio of 0.91 +/- 0.36 for the subpulmonary to
      subaortic length of the outlet septum was significantly less than the value of
      1.54 +/- 0.41 noted previously in hearts with tetralogy of Fallot (p less than
      0.001).

PMID- 1998417
TI  - Superiority of retrograde cardioplegia after acute coronary occlusion.
AB  - Because antegrade cardioplegia may limit the distribution of cardioplegia beyond
      a coronary occlusion, this study was undertaken to determine whether retrograde
      coronary sinus cardioplegia provides superior myocardial protection during
      revascularization of an acute coronary occlusion. In 20 adult pigs, the second
      and third diagonal branches were occluded with a snare for 1 1/2 hours. Animals
      were then placed on cardiopulmonary bypass and underwent 30 minutes of ischemic
      arrest with multidose, potassium, crystalloid cardioplegia. In 10 animals, the
      cardioplegia was given antegrade through the aortic root, whereas in 10 others,
      it was given retrograde through the coronary sinus. After the arrest period, the
      coronary snares were released and all hearts were reperfused for 3 hours.
      Postischemic damage in the myocardium beyond the occlusions was assessed by wall
      motion scores using two-dimensional echocardiography (4 = normal to -1 =
      dyskinesia), the change in myocardial pH from preischemia, and the area of
      necrosis/area of risk (histochemical staining). Hearts protected with retrograde
      coronary sinus cardioplegia had less tissue acidosis (change in pH = 0.08 +/-
      0.03 versus 0.41 +/- 0.13; p less than 0.05), higher wall motion scores (2.0 +/-
      0.6 versus 1.3 +/- 0.3; not significant), and less myocardial necrosis (43.4% +/-
      3.6% versus 73.3% +/- 3.5%; p less than 0.0001). We conclude that retrograde
      coronary sinus cardioplegia provides more optimal myocardial protection than is
      possible with antegrade cardioplegia after revascularization of an acute coronary
      occlusion.

PMID- 1998418
TI  - Efficacy of coronary sinus cardioplegia in patients with complete coronary artery
      occlusions.
AB  - Myocardial areas distal to complete coronary artery occlusions are poorly
      protected by antegrade cardioplegia. We assessed the effects of coronary sinus
      cardioplegia in 30 patients undergoing bypass operations and at high risk of
      cardioplegic maldistribution because of the following anatomical patterns of
      coronary artery disease: critical (greater than or equal to 50%) stenosis of the
      left main trunk with total occlusion of the right coronary artery (16 patients)
      or critical (greater than or equal to 70%) stenosis of the right coronary artery
      with total occlusion of the left anterior descending (11 patients) or circumflex
      artery (3 patients). After induction of arrest through the aorta, coronary sinus
      cardioplegia was given intermittently during the cross-clamp period at a flow
      rate of 100 mL/min. Intraoperatively, occluded arteries were consistently found
      to be filled with the retrogradely infused solution. One patient died early
      postoperatively of low cardiac output and a second patient died later during his
      hospital stay, presumably of an arrhythmia. At autopsy, none of them had
      pathological evidence of inadequate myocardial protection. One patient sustained
      a myocardial infarction and 3 others required inotropes for more than 24 hours
      postoperatively. Postoperative values for right and left stroke volume indices
      were not significantly different from prebypass levels. Overall, these results
      are consistent with the occurrence of limited intraoperative ischemic damage and,
      by inference, suggest the efficacy of the coronary sinus route in preserving
      myocardial areas supplied by completely occluded coronary arteries and, hence, in
      jeopardy of inadequate cardioplegia delivery.

PMID- 1998419
TI  - Replacement of the aortic valve or root with a pulmonary autograft in children.
AB  - Between January 1967 and December 1988, 34 patients ranging in age from 3 to 18
      years (mean, 14 +/- 3.6 years) underwent replacement of the aortic valve or root
      with their own pulmonary valve. The indication for operation was left ventricular
      outflow obstruction in 16 patients (47%), aortic regurgitation in 14 (41%), mixed
      aortic valve disease in 3 (9%), and failure of a previously implanted aortic
      homograft in 1 (3%). There were four early deaths, all before 1971, giving a
      hospital mortality of 11.8% (70% confidence interval, 6% to 20%). Surviving
      patients have been followed up a cumulative total of 214 patient-years, the
      longest period of observation being 16 years 8 months. Late mortality was 13.3%
      (70% confidence interval, 7% to 23%), and 4 other patients required removal of
      the pulmonary autograft for endocarditis. Actuarial rates at 16 years were 74% +/
      11% for freedom from reoperation on the left ventricular outflow tract, 80% +/-
      10% for freedom from reoperation on the right ventricular outflow tract, and 77%
      +/- 10% for late survival. There was no instance of primary structural
      degeneration in the pulmonary autograft, and all surviving patients were in New
      York Heart Association functional class I without medication. This experience
      demonstrates that the pulmonary autograft can achieve good early and medium-term
      results in young patients. Should growth potential be realized, it might
      constitute the ideal biological valve for the left ventricular outflow in
      children.

PMID- 1998421
TI  - Management of aortic insufficiency in chronic aortic dissection.
AB  - From January 1980 to December 1988, 44 patients with chronic aortic dissection
      and aortic insufficiency underwent operation. This group of patients was analyzed
      to evaluate the outcome of those in whom the aortic valve was preserved compared
      with those having valve replacement. The overall preoperative characteristics of
      the two groups were similar except for the incidence of Marfan's syndrome. Valve
      replacement was the elected procedure in patients with valve degeneration or
      annuloaortic ectasia. In patients with leaflet prolapse with or without an
      enlarged annulus, a plastic procedure was used. In 48% of the patients, it was
      possible to preserve the valve. There were five hospital deaths (11%): three were
      due to low-output syndrome, one was due to bleeding, and one was due to
      neurological complications. There were two late deaths (5%). Follow-up of the 37
      surviving patients ranged from 2 to 108 months (mean follow-up, 18 months).
      Seventy-eight percent of the survivors were in functional class I and the others
      were in class II. Two patients in whom the aortic valve was preserved had mild
      aortic insufficiency. Three patients with bioprostheses underwent reoperation
      because of prosthetic valve dysfunction. One patient who had aortoplasty and an
      aortic valve plastic procedure was seen with redissection and aortic
      insufficiency after 60 months and was reoperated on using the Bentall technique.
      The actuarial survival curves showed that patients who underwent valvoplasty had
      higher, but not significantly higher, survival rates than the valve replacement
      patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1998420
TI  - Failure of Hancock pericardial xenografts: is prophylactic bioprosthetic
      replacement justified?
AB  - The incidence of major valve-related complications was evaluated in a series of
      patients in whom the Hancock pericardial xenograft was used for aortic (AVR; n =
      84), mitral (MVR; n = 17) and mitral-aortic (MAVR; n = 13) valve replacement. At
      7 years actuarial survival is 66% +/- 8% after AVR, 64% +/- 13% after MVR, and
      41% +/- 15% after MAVR, whereas actuarial freedom from valve-related death is 79%
      +/- 7% after AVR, 78% +/- 13% after MVR, and 81% +/- 12% after MAVR. Actuarial
      freedom from thromboemboli and anticoagulant-related hemorrhage at 7 years is 93%
      +/- 4% and 98% +/- 2% after AVR and 83% +/- 10% and 88% +/- 11% after MVR; no
      such complications occurred after MAVR. Structural valve deterioration determined
      at reoperation, at autopsy, or by clinical investigation was observed in 34
      patients with AVR (10.0 +/- 0.2%/patient-year), in 10 with MVR (10.6 +/-
      3.3%/patient-year), and in 9 with MAVR (16.6 +/- 5.5%/patient-year). After AVR,
      19 patients underwent reoperation and 2 died before reoperation; 4 patients with
      MVR underwent reoperation, and 7 patients with MAVR underwent reoperation and 1
      died before reoperation. Seventy-eight percent of the current survivors (13
      patients with AVR, 7 with MVR, and 1 with MAVR) have clinical evidence of valve
      failure. At 7 years actuarial freedom from structural deterioration of the
      Hancock pericardial xenograft is 25% +/- 7% after AVR, 29% +/- 14% after MVR, and
      0% after MAVR.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1998422
TI  - Postcardiotomy mechanical circulatory support in the elderly.
AB  - The role of mechanical circulatory support after cardiac operations in elderly
      patients is not clearly established. Between November 1985 and July 1989, 18
      patients 65 years of age or older (mean age, 71 years; range, 65 to 82 years)
      were treated after cardiotomy with a centrifugal vortex or pneumatic mechanical
      ventricular assist device. This group comprised 1.9% of the 926 patients 65 years
      of age or older undergoing cardiac surgical procedures and 69% of the 26 patients
      requiring postcardiotomy support during this interval. Before institution of
      mechanical support, all patients were receiving maximal inotropic support and 16
      patients had intraaortic balloon pumps inserted. Univentricular support was used
      in 9 patients (6 left, 3 right) and biventricular support in 9 patients. The mean
      duration of support was 45 hours (range, 8 to 118 hours). Twelve patients (67%)
      were successfully weaned, 8 (44%) were discharged from the hospital, and 6 (33%)
      remain alive 11 to 31 months postoperatively. Four of the 6 survivors are in New
      York Heart Association class I, 1 is in class II, and 1 is in class IV. The
      Combined Registry for ventricular assist device support has recently reported an
      overall survival rate of 12% in patients 65 to 70 years of age and 6% in those
      older than 70 years. Our results are comparable with those reported for younger
      patients and justify the use of postcardiotomy ventricular assist device support
      in the elderly.

PMID- 1998423
TI  - Risk factors for cardiac operations in adult Jehovah's Witnesses.
AB  - During a 27-year-period, 663 adults of the Jehovah's Witness faith underwent open
      heart procedures at the Texas Heart Institute. To determine the effect of recent
      changes in operative techniques and in the patient population itself on early
      mortality, we reevaluated the surgical outcome in this special group of patients.
      We reviewed the charts of 88 consecutive Jehovah's Witness patients who had an
      open heart operation between January 1986 and March 1989 and compared demographic
      variables in this group with those of 575 patients who underwent operation
      between May 1963 and January 1986. In our recent series, patients were older
      (mean age, 61 years versus 54 years), and 16% were seen for repeat procedures.
      Early mortality (less than or equal to 30 days postoperatively) was lower in the
      recent series than in the earlier series (7.0% versus 10.7%), but the difference
      between the groups was not statistically significant. We identified several
      important factors associated with an increased risk of early death in the recent
      group of patients. These factors included repeat cardiac operations (p less than
      0.01), especially for valvar dysfunction, severe left ventricular dysfunction
      (defined as an ejection fraction less than 0.35) (p less than 0.01), and a
      hemoglobin level lower than 80 g/L (8 g/dL) (p less than 0.01) on postoperative
      day 1. Although blood loss remains the leading cause of death in these patients,
      cardiac operations can be performed with an acceptable mortality.

PMID- 1998424
TI  - Hemodynamic effects of lobar pulmonary artery occlusion in a porcine sepsis
      model.
AB  - We induced severe pulmonary hypertension and acute lung injury in 6 pigs by
      Pseudomonas aeruginosa infusion. We studied the effect of pulmonary artery
      catheter inflation of a pulmonary artery catheter balloon in the left lower lobar
      pulmonary artery was accompanied by a significant (p less than 0.05, paired t
      test) increase in pulmonary artery pressure, a decrease in left atrial pressure,
      a decrease in cardiac output, and a decrease in mean arterial pressure. No
      significant changes occurred when the catheter was advanced into the wedged
      position without balloon inflation. Balloon inflation had no significant effect
      on these variables before bacterial infusion. We conclude that with sufficiently
      severe pulmonary hypertension in association with diffuse lung injury, lobar
      pulmonary artery occlusion may cause alterations in cardiac output and left
      atrial pressure. This may confuse interpretation of pulmonary artery catheter
      measurements.

PMID- 1998425
TI  - Reoperation for persistent outflow obstruction in hypertrophic cardiomyopathy.
AB  - This study compares results of a second left ventricular myotomy and myectomy (M
      + M) with those of mitral valve replacement (MVR) as reoperative procedures for
      persistent left ventricular outflow obstruction after M + M in hypertrophic
      cardiomyopathy. Comparison of the second M + M group (n = 12) with the MVR group
      (n = 11) disclosed significant difference (p less than 0.05) in mean age at the
      initial operation (29 +/- 11 years versus 40 +/- 8 years), interval between
      operations (46 +/- 57 months versus 18 +/- 13 months), and age at reoperation (33
      +/- 10 years versus 42 +/- 8 years); and insignificant differences in mean
      preoperative functional class, cardiac index, left ventricular outflow gradients
      at rest or with provocation, and hospital mortality at reoperation (2/12 versus
      1/11). At 6 months after reoperation, comparison of results of a second M + M
      with MVR showed that mean functional class, cardiac index, and left ventricular
      outflow gradient at rest were similarly improved, but the outflow gradient with
      provocation was significantly higher in the second M + M group (57 +/- 44 mm Hg
      versus 14 +/- 9 mm Hg, p less than 0.05). Total follow-up was 108 patient-years
      (100% complete) with an average of 5.9 years per patient in the second M + M
      group and 3.4 years per patient in the MVR group. Actuarial survival, including
      hospital mortality, at 3 and 5 years was 83% and 76%, respectively, after the
      second M + M, which was similar to 92% and 77% after MVR.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1998426
TI  - Thoracoscopic debridement and pleural irrigation in the management of empyema
      thoracis.
AB  - As a sequel to a paper reporting good results obtained in 12 patients with
      empyema thoracis treated by thoracoscopic debridement and irrigation in our
      department, subsequent experience with a further 18 patients is reported.
      Drainage of pus and irrigation resulted in resolution of pyrexia with improvement
      in general condition in all patients. Overall, complete resolution was obtained
      by this technique alone in 60% (18/30). Of the 12 patients in whom complete
      resolution was not obtained, secondary surgical measures resulted in resolution
      of empyema in 8. Four patients died; all were elderly and severely debilitated, 3
      with advanced malignancy. Their deaths were not related to the technique, which
      was well tolerated in all cases. Thoracoscopic debridement and irrigation used
      routinely as a first-line measure in empyema thoracis is a safe and relatively
      atraumatic procedure, does not exclude the use of any subsequent surgical
      measure, and provides valuable time to improve the condition of debilitated
      patients so that they may tolerate more aggressive surgical procedures.

PMID- 1998427
TI  - Computed tomography-guided minithoracotomy for the resection of small peripheral
      pulmonary nodules.
AB  - Small peripheral pulmonary nodules ranging in size from 1 mm to 20 mm were
      excised in 58 patients. Computed tomography was used to mark the skin overlying
      the nodules to minimize the surgical exposure needed for operative
      identification. The nodules were 1 cm or less in maximum diameter in 76% of the
      patients. Twenty-six patients had single nodules and 32 patients had multiple
      nodules. The preoperative diagnosis was inaccurate in 67% of the patients. In 61%
      of the patients in whom malignancy was suspected, no tumor was demonstrated.
      Conversely, of the 20 patients in whom a malignant nodule was excised, the
      preoperative diagnosis was correct in only 50%. Thirty-one patients required no
      further treatment apart from their biopsy and 27 required additional
      intervention. Small peripheral pulmonary nodules require biopsy for diagnosis.
      When percutaneous needle aspiration biopsy is unsuccessful, or technically
      difficult, a computed tomography-guided thoracotomy is an effective and minimally
      invasive surgical alternative.

PMID- 1998428
TI  - Combined myocardial revascularization and abdominal aortic aneurysm repair.
AB  - Myocardial infarction remains the leading cause of early and late deaths after
      abdominal aortic reconstruction in patients with abdominal aortic aneurysm. Our
      approach for the past 4 years has been combined myocardial revascularization with
      abdominal aortic aneurysm repair in patients with good left ventricle
      performance. From July 1984 through June 1989, 128 patients underwent abdominal
      aortic aneurysm repair. Seventeen patients underwent combined abdominal aortic
      reconstruction with coronary artery bypass grafting. One patient died (5.9%). The
      remaining patients are all well at current follow-up. Our experience shows that
      patients with coronary artery disease and abdominal aortic aneurysm may have both
      lesions safely repaired as a single operative procedure.

PMID- 1998429
TI  - Strut fixation of an extensive flail chest.
AB  - The indications for and preferred approaches to operative stabilization of
      posttraumatic chest wall instability are uncertain. We suggest this simple,
      rapid, and effective approach to surgical stabilization by Luque rod strutting of
      the flail segment when operation is required.

PMID- 1998430
TI  - Left ventricular pseudoaneurysm with hemoptysis.
AB  - A 53-year-old man who had previously undergone resection of a left ventricular
      aneurysm was admitted because of hemoptysis. Preoperative evaluation with
      computed tomographic scan and cardiac catheterization demonstrated a
      pseudoaneurysm of the inferior ventricular wall measuring 16 cm in diameter with
      protrusion into the left hemithorax. The neck of the pseudoaneurysm was a defect
      in the ventricular wall extending from the base of the mitral valve annulus to
      the insertion of the posterior papillary muscle. Operative repair was performed
      using an albumin-coated, low-porosity Dacron patch.

PMID- 1998431
TI  - An unusual complication of cardiac transplantation--infected aortic
      pseudoaneurysm.
AB  - Infections after cardiac transplantation are a frequent cause of early morbidity
      and mortality. An unusual site for such a complication is at the aortic
      anastomotic suture line. We report a case of an infected aortic pseudoaneurysm,
      seen as recurrent septicemia, during the first 6 months after cardiac
      transplantation.

PMID- 1998432
TI  - Procainamide-induced respiratory insufficiency after cardiopulmonary bypass.
AB  - A 46-year-old man could not be weaned from ventilatory support while receiving
      procainamide. When the drug was discontinued, the patient was successfully weaned
      shortly thereafter.

PMID- 1998433
TI  - Repair of posterior left ventricular aneurysm in a six-year-old boy.
AB  - Left ventricular aneurysms and diverticula are rarely encountered in the
      pediatric age group. This paper reports a case of congestive heart failure and
      mitral regurgitation in a 6-year-old boy with a large posterolateral left
      ventricular aneurysm. Complete repair was successfully performed by excision of
      the aneurysm and Dacron patch reconstruction of the left ventricular free wall.
      The patch extended onto the posterior annulus of the mitral valve, thus restoring
      the mitral valve to normal geometry and correcting the mitral insufficiency. The
      surgical literature on congenital cardiac diverticula and acquired aneurysms in
      children is reviewed and summarized.

PMID- 1998434
TI  - Carcinosarcoma of the lung with hypertrophic pulmonary osteoarthropathy.
AB  - Carcinosarcoma of the lung is a rare malignancy. Endobronchial and parenchymal
      variants are classically described. Clinicopathological features are often
      related to anatomical location, as is the case for most lung neoplasms. This case
      report details the surgical management of a carcinosarcoma in a patient seen with
      pulmonary osteoarthropathy.

PMID- 1998435
TI  - Hemolysis due to branch pulmonary stenosis after the arterial switch procedure.
AB  - An infant with d-transposition of the great arteries underwent arterial switch
      operation using the modified Jatene technique. Severe bilateral branch pulmonary
      artery stenosis and mechanical hemolysis subsequently developed. The hemolysis
      resolved after surgical repair of the stenotic arteries. Probable causes are
      discussed.

PMID- 1998436
TI  - Surgical management of carcinoid heart disease.
AB  - Metastatic carcinoid tumor is often seen with flushing, diarrhea, and cardiac
      symptoms--the carcinoid syndrome. Cardiac failure is often associated with major
      morbidity and mortality in carcinoid disease. In this report, a case of
      successful cardiac valvar surgical intervention has resulted in prolonged
      alleviation of cardiac symptoms and survival.

PMID- 1998437
TI  - False aneurysm formation of the great arteries after arterial switch operation.
AB  - An infant with simple transposition of the great arteries underwent a two-staged
      arterial switch operation, after which mediastinal infection occurred. Continuous
      irrigation with povidone-iodine solution was performed for 10 days. After that,
      the patient experienced life-threatening hemorrhage three times. At the time of
      the second hemorrhage, greater omental transfer was performed. On postoperative
      day 109, false aneurysm was recognized, having developed from both great
      arteries. Successful repair was performed on postoperative day 110.

PMID- 1998438
TI  - Adenocarcinoma arising in a foregut cyst of the mediastinum.
AB  - A case of malignant transformation in a mediastinal cyst of the esophageal
      reduplication type is presented. The cyst had been recognized 39 years
      previously, but remained asymptomatic until sudden growth occurred. It was
      resected totally from the esophagus and the patient recovered well. A review of
      the literature showed that malignancy in mediastinal foregut cysts is extremely
      rare.

PMID- 1998439
TI  - Mammary artery grafts: a new no-touch technique for anastomosis.
AB  - Reported techniques for mammary artery-coronary artery anastomosis involve
      instrumental damage to one or all three layers of the mammary artery during
      surgical connection. Described herein is an atraumatic method of suturing that
      achieves a precise and highly accurate anastomosis.

PMID- 1998440
TI  - Silicone pouch for protection of automatic implantable cardioverter-defibrillator
      leads.
AB  - Automatic implantable cardioverter-defibrillator has become routine treatment for
      recurrent, drug-resistant ventricular tachycardia. Although there is
      documentation regarding clinical experience and device performance, there is
      little information on how to avoid complications related to the retrieval of
      sensing and defibrillation leads from the subcutaneous space. We are reporting
      our experience with a silicone pouch for protection of automatic implantable
      cardioverter-defibrillator leads that allows immediate and simple retrieval of
      the leads in case an automatic implantable cardioverter-defibrillator generator
      is needed.

PMID- 1998441
TI  - Single venous cannulation through the right atrium for venous return in valve
      operations.

PMID- 1998442
TI  - Autogenous atrial tunnel for direct cavopulmonary connection in infants and small
      children.
AB  - A technique is described for construction of an autogenous right atrial tunnel
      for direct cavopulmonary connection in infants and small children requiring
      Fontan operation. Advantages, in this subset of patients, of this method over
      others previously described using prosthetic or growth-limited materials are
      suggested.

PMID- 1998443
TI  - Jatene's arterial repair for transposition of the great vessels.

PMID- 1998444
TI  - Fistulas between the aorta and tracheobronchial tree.
AB  - Aortobronchial fistula is a rare condition that is invariably fatal if not
      diagnosed and surgically treated. With appropriate surgical intervention,
      survival rates greater than 70% can be achieved. A review of the literature and
      an illustrative case report are presented. A total of 63 fistulas in 62 patients
      have been described. The case we present is unusual in the use of serratus
      anterior muscle for repair of the fistula. Eighty-seven percent of the cases
      documented in the literature were associated with an aneurysm of the thoracic
      aorta. Eighty-six percent of the fistulas were between the descending aorta and
      left bronchopulmonary tree. More than 95% of patients experienced at least a
      single episode of hemoptysis, and massive hemoptysis occurred in more than half
      of the reported cases. A correct preoperative diagnosis was made in only 54% of
      cases. Plain chest radiographs definitively demonstrated an aneurysm in only 16%.
      The computed tomographic scan was the most rewarding test, identifying an
      aneurysm in 11 of 12 patients and the fistula in 50% of them. Surgical repair
      resulted in a 76% survival rate.

PMID- 1998445
TI  - Mediastinal masses.

PMID- 1998446
TI  - Risk of reintervention after coarctation repair.

PMID- 1998447
TI  - Membranotomy for Budd-Chiari syndrome.

PMID- 1998448
TI  - The first mitral valve replacement.

PMID- 1998449
TI  - Hemolysis after valve repair.

PMID- 1998450
TI  - Muscle rehabilitation in impaired elderly nursing home residents.
AB  - Based on observations of changes in muscle function associated with aging, and
      the exacerbation of these changes with frailty, a program of muscle strengthening
      has been developed to correct specific defects in muscles. This pilot study was
      undertaken on 18 functionally impaired nursing home residents (age range 60 to 90
      years) with markedly deteriorated muscle function (50%) secondary to age, disuse,
      and multiple chronic illnesses. Fourteen of the subjects completed the six-week
      program without adverse effects. In 75% of the patients, there was improved
      muscle function, with endurance, strength, and speed increasing 35%, 15%, and
      10%, respectively. After the program, many subjects increased their spontaneous
      activity and decreased their dependency. The improvements were still evident four
      months after rehabilitation. These results suggest that it may be possible,
      through a carefully supervised, short-term program of muscle rehabilitation, for
      nursing home residents to achieve an enhanced level of physical functioning.

PMID- 1998451
TI  - Evaluation of treatment protocols on minimal to moderate spasticity in multiple
      sclerosis.
AB  - Thirty men and women diagnosed with definite multiple sclerosis (MS) were treated
      for ten weeks in a blinded, cross-over study. Patients with minimal to moderate
      spasticity were randomized to one of three sequences to evaluate the effects on
      MS-related spasticity of baclofen alone, stretching regimen with placebo, placebo
      alone, and stretching regimen with baclofen. The Cybex II isokinetic unit, timed
      gait, Ashworth scale, and subject's assessment of function were objective and
      subjective measures used to evaluate changes in hypertonicity. There was
      significant correlation between the Cybex and Ashworth as methods of measuring
      spasticity. Overall, treatment with baclofen alone significantly improved
      moderate quadriceps spasticity as measured by Cybex flexion scores. A trend,
      indicative of enhancing the beneficial effects of baclofen, was noted when
      stretching exercises were added to the treatment.

PMID- 1998452
TI  - Quantitative gait analysis in unilateral and bilateral total hip replacements.
AB  - By qualitative and quantitative analysis of gait we evaluated the outcomes in 41
      patients after total hip arthroplasty for degenerative arthritis. Patients with
      unilateral and bilateral degenerative hip disease were evaluated in an effort to
      characterize preoperative and postoperative gait characteristics. Patients were
      evaluated using a subjective hip-rating scale and a gait-evaluation mat. Data
      were compared with those obtained from a control group of 91 patients. All
      patients showed a marked improvement in both subjective ratings and measured
      quantitative gait parameters. Patients with unilateral hip disease improved to a
      greater extent than those with bilateral disease after arthroplasty. We have
      concluded that total hip arthroplasty can greatly improve the gait
      characteristics of patients with degenerative arthritis, and that this
      improvement can be quantified, documented, and followed by using a system of gait
      evaluation.

PMID- 1998453
TI  - Anemia after traumatic spinal cord injury.
AB  - The incidence and natural history of anemia in patients with spinal cord injuries
      (SCI) were investigated in a prospective study of 68 patients consecutively
      admitted to a regional acute SCI unit. Fifty had SCI and 18 had spine injuries
      (SI) without neurologic deficit. Thirty-six of 41 males (88%) and six of nine
      females (67%) with SCI were anemic on at least one occasion. In the first two
      weeks after injury, in females and in males, there was no significant difference
      in mean hemoglobin level between SI and SCI patients. At six weeks, no male with
      SI was anemic, and males with SCI had significantly lower mean hemoglobin levels
      than those with SI (121.6 g/L vs 145.4 g/L, p less than .001). Identified early
      causes of anemia were blood loss due to bony soft tissue or visceral injury,
      gastrointestinal bleeding, and surgery. In the postacute phase (more than six
      weeks after injury), anemia occurred in 25 of 41 male and three of nine female
      SCI patients, and its occurrence was associated with the presence of an
      identified chronic disease, especially urinary tract infection.

PMID- 1998454
TI  - Sexual changes in hemiparetic patients.
AB  - Eighty-six patients, each with hemiparesis caused by a single stroke, were
      studied to assess the changes in sexual life experienced after the onset of the
      illness. Clinical data were collected, and a questionnaire concerning both sexual
      behavior and feelings about sexuality was administered to the patients and their
      spouses. Twenty-four couples were eliminated from further analysis because of a
      discrepancy between husband and wife in the answers concerning sexual behavior
      after stroke. A marked decline in sexual activity after stroke was found in both
      genders; other aspects of sexual behavior underwent fewer changes. The feeling of
      an overall change in sexual life was reported more frequently by male patients.
      Most patients' spouses reported the feeling of an overall psychological change in
      their partners and the feeling of an overall change in sexual life after the
      onset of the illness. No significant associations were found between clinical
      features and changes in sexual life. This study confirms that cerebrovascular
      accidents are generally followed by some important alterations in sexual life.
      Clinical factors do not seem to play a crucial role in determining these changes,
      which may be better explained in terms of maladjustment attributable to
      psychologic and interpersonal factors.

PMID- 1998455
TI  - Recurrent thoracic outlet syndrome after first rib resection.
AB  - Seventy-seven patients with 84 operated limbs participated in a follow-up
      examination on an average of about six years after the resection of the first rib
      for thoracic outlet syndrome (TOS). Forty-two limbs (50%) were totally
      asymptomatic one month after the operation and remained so for at least half a
      year postoperatively. In the follow-up examination, 31 limbs were still
      asymptomatic, whereas 11 limbs had the same symptoms as before the operation. Of
      the nine patients with recurrent TOS (two with bilateral resection), seven were
      women and two were men. These nine patients were on average 38 years old (range =
      19 to 51 years) and their jobs consisted of monotonous desk work. Seven of 11
      stumps of the first rib were subluxated disclosed by the cervical rotation
      lateral-flexion test. The occurrence of a subluxated stump of the first rib in
      the group of asymptomatic patients was far lower, only 3% (p less than .001). Of
      the 42 patients with persistent problems, a subluxated stump was encountered in
      seven (17%). Results of this follow-up examination suggest that monotonous desk
      work is an important factor causing kinesiologic abnormalities in the thoracic
      aperture. This abnormal kinesiology contributes to the recurrence of TOS symptoms
      even after the resection of the first rib.

PMID- 1998456
TI  - Wrist flexion as an adjunct to the diagnosis of carpal tunnel syndrome.
AB  - The effects of five minutes of wrist flexion on median motor and sensory evoked
      potential latencies in 87 individuals were studied. Nineteen subjects had carpal
      tunnel syndrome (CTS) as diagnosed by increased median nerve latencies across the
      wrist, and 68 had values in the normal range and were assigned to the control
      group. A slight prolongation of up to 0.5m sec of evoked potential latencies was
      observed in both groups after flexion, but the differences between the two groups
      were not significant to establish the value of adding wrist flexion to
      conventional screening methods.

PMID- 1998457
TI  - Detecting lower motor neuron dysfunction of the pharynx and larynx with
      electromyography.
AB  - This study assessed the utility of clinical electromyography (EMG) for detecting
      lower motor neuron (LMN) or upper motor neuron (UMN) dysfunction affecting the
      intrinsic muscles of the larynx and pharynx. Twenty-nine subjects were examined;
      their clinical diagnoses included perioperative nerve injury, cerebral
      infarction, and lateral medullary infarction. Resting activity, motor unit action
      potential (MUAP) morphology, and MUAP recruitment were evaluated in every case.
      Medical records (excluding EMG data) were analyzed for clinical evidence of LMN
      or UMN dysfunction in the intrinsic muscles of the larynx and pharynx. The
      diagnosis of LMN dysfunction rested on clinical data consistent with cranial
      nerve injury, poliomyelitis, Wallenberg syndrome, or unilateral bulbar palsy.
      Criteria for UMN dysfunction included previous cerebral (not brainstem)
      infarction or mass lesion or the presence of hemiparesis. Electromyographic
      abnormalities were significantly associated with LMN dysfunction (p less than
      .05), but they were not significantly associated with UMN dysfunction. Of the
      parameters tested, MUAP recruitment was the most sensitive (82%) and specific
      (92%).

PMID- 1998458
TI  - Neurobehavioral effects of phenytoin, carbamazepine, and valproic acid:
      implications for use in traumatic brain injury.
AB  - Due to the risk of posttraumatic epilepsy, phenytoin, carbamazepine, and valproic
      acid are often prescribed for patients with traumatic brain injury (TBI). In this
      review the literature is examined for evidence of neurobehavioral impairment due
      to carbamazepine, phenytoin, and valproic acid. No comparative studies have been
      performed in the TBI population, making if difficult to determine if one of these
      medications is preferable. Direct inference from studies on epilepsy patients to
      TBI patients is hazardous due to underlying differences in the two populations.
      Reported findings for epilepsy patients are subtle and not consistent across
      studies. All three drugs appear to exert some effect on cognitive and motor
      functions in epileptic patients, and these impairments worsen at increasing serum
      levels. The varied length of experience with each drug makes it difficult to
      assign relative weight to the evidence for or against each. A comparative
      assessment of cognitive and behavioral effects of anticonvulsants should be done
      in the TBI population.

PMID- 1998459
TI  - Electrophysiologic investigation of mandibular nerve injury.
AB  - Isolated lesions of the mandibular branch of the trigeminal nerve have only
      rarely been reported. We report the occurrence of an isolated lesion of the
      mandibular nerve associated with a unilateral mandibular fracture, and its
      substantiation electrophysiologically. A 65-year-old man was involved in a motor
      vehicle accident resulting in multiple fractures, including a unilateral
      mandibular fracture and temporomandibular joint dislocation. No evidence of
      intracranial pathology by CT scan was noted and the neurologic examination was
      nonfocal except for dysfunction of the mandibular nerve ipsilateral to the
      fracture site. Bilateral facial nerve latency and blink reflexes were normal. EMG
      evaluation of the muscles of facial expression and mastication demonstrated
      denervation confined to the muscles innervated by the mandibular branch of the
      trigeminal nerve. In patients complaining of facial sensory dysfunction,
      malocclusion, or weakness of muscles of mastication after mandibular fracture, an
      electrophysiologic examination can assist in evaluating cranial nerve integrity.

PMID- 1998460
TI  - Dural spinal cord arteriovenous malformation.
AB  - After multiple hospital admissions and an inpatient rehabilitation stay, a 68
      year-old woman was transferred to our rehabilitation facility with a paraparesis
      of unknown etiology. Previous studies included four CT scans and three MRIs which
      did not demonstrate the lesion. A myelogram was noncharacteristic. The correct
      diagnosis, confirmed by selective angiography, was ultimately contingent upon
      recognition of the clinical features and natural history of dural spinal cord
      arteriovenous malformations (SCAVM). The unusual combination of this multitude of
      nondiagnostic imaging studies in the uncommon dural SCAVM served to delay
      diagnosis and treatment. Such delay may have great functional consequences. This
      report illustrates the importance of suspecting SCAVM and recognizing its
      features. Emphasis is placed on the physiatrist's role in assuring proper
      diagnosis to expedite a timely treatment and to obtain the best functional
      outcome. A brief review of the classification, clinical features,
      pathophysiology, diagnosis, and prognosis of SCAVM is presented.

PMID- 1998461
TI  - A cellist with arm pain: thermal asymmetry in scalenus anticus syndrome.
AB  - We report on a cellist with pain and coldness of the upper extremity. Abnormal
      thermographic studies were instrumental in uncovering intermittent compression of
      the subclavian artery, and this prompted us to study the effects of cello playing
      on skin temperature asymmetry. Temperature asymmetry was defined as the
      temperature difference (delta-T) from one hand to the other. In 57 controls, mean
      delta-T at rest was .309 +/- .254C. Exercising the upper extremities by prolonged
      elbow flexion or by movements mimicking cello playing in controls did not
      significantly affect delta-T. In our patient, delta-T was ten times control
      (3.6C). Angiography showed extrinsic compression of the subclavian artery
      occurring only after cello playing; sympathetic ganglion block relieved the pain.
      Our patient's abnormal skin temperature may have reflected sympathetic vasomotor
      hyperactivity. Intermittent neurovascular compression and sympathetic
      hyperactivity appear to be factors in scalenus anticus syndrome.

PMID- 1998462
TI  - Candida pyelonephritis complicating traumatic C5 quadriplegia: diagnosis and
      management.
AB  - We present the first reported case of Candida pyelonephritis in a spinal cord
      injured patient. In addition to multiple courses of empiric antibiotics, the
      neurogenic bladder and alteration in cell-mediated immunity found in spinal cord
      injured patients may have increased this patient's susceptibility to fungal
      disease. A 50-year-old patient with C5 motor functional quadriplegia developed
      Candid albicans pyelonephritis while undergoing rehabilitation. The patient had
      several surgical procedures and multiple courses of antibiotic therapy during
      acute hospitalization. He continued to have a hectic fever curve, leukocytosis
      with increased band forms, lethargy, and progressive uremia during
      rehabilitation. Successful investigation of the patient's condition included
      assessment of serologic tests for Candida precipitin antigen; multiple blood and
      urine cultures; exclusion of other causes of hectic fever; abdominal computerized
      tomogram, which revealed a left kidney hypodensity with irregular margins; and a
      retrograde pyelogram, which demonstrated multiple renal pelvic-filling defects.
      Cystoscopically placed ureteral stents, which relieved the genitourinary
      obstruction, drained gross pus from which Candida albicans was cultured; the
      patient was treated with amphotericin B and showed clinical improvement.
      Pathogenesis, presentation, diagnosis, and treatment of Candida pyelonephritis
      are reviewed.

PMID- 1998463
TI  - Spinal accessory nerve palsy: an unusual complication of coronary artery bypass.
AB  - The neurologic complications of coronary artery bypass surgery have been well
      documented, with a reported incidence of 61% in one large study. Most injuries to
      the peripheral nervous system involve the brachial plexus. We report the first
      case of a spinal accessory nerve lesion after coronary bypass surgery. The
      patient presented with progressive right shoulder weakness. Electrodiagnostic
      studies revealed a partial lesion of the right spinal accessory nerve. Physical
      therapy, including strengthening, range of motion, and electric stimulation to
      the right shoulder, was prescribed to assist recovery of strength and function.
      Repeat electrodiagnostic studies confirmed nerve regeneration. Prompt recognition
      of spinal accessory nerve damage after coronary bypass surgery is essential.
      Early rehabilitation will improve the chances of a better functional outcome.

PMID- 1998464
TI  - The "Z" strap: harnessing modification for patients with upper extremity
      amputations.
AB  - High level, upper extremity amputees have been observed to have problems
      affecting overall prosthetic function. These include: tendency of the
      Northwestern Ring to ride upward and difficulty with terminal device function
      above 90 degrees of elbow flexion. A simple modification of the control strap was
      tried to resolve these problems of function. The control strap was attached
      across the back to a buckle on the unamputated side at the shoulder to provide a
      more efficient anchor. This created more body contact across the back and formed
      a type of "Z" strap allowing full freedom of movement in any direction. Less
      forward shoulder flexion was necessary due to decreased cable travel and because
      the strap was not sliding up and over the shoulder. A single case study is
      described and the successful outcome for the amputee.

PMID- 1998465
TI  - The town-gown syndrome. An ancient disease, as yet uncured.

PMID- 1998466
TI  - Graduate surgical education from a 'town' perspective.

PMID- 1998467
TI  - Operative exposure of the abdominal arteries for trauma.
AB  - Traumatic injuries to the abdominal arteries require operative exposures that
      allow for flexible repair. Dividing the abdominal arterial tree into four zones,
      based on exposure, provides expedient and precise repair of all major abdominal
      arteries.

PMID- 1998469
TI  - Simplified hepatic resection with the use of prolonged vascular inflow occlusion.
AB  - Ten consecutive patients scheduled to undergo liver resection were studied
      prospectively with the use of a standard protocol, which included routine
      vascular inflow occlusion to reduce blood loss and blood transfusion
      requirements. Fibrin sealant was sprayed on the raw liver surface, and abdominal
      drainage was not performed. No deaths occurred, and the postoperative course was
      remarkably smooth. The normothermic liver ischemic times of 30 to 122 minutes
      (mean, 73 minutes) were well tolerated. The amount of blood transfused was
      reduced to a mean of 2 U (range, 0 to 4 U). The occurrence of infected
      intraabdominal bile collections in two patients with preexisting biliary tract
      infection suggested that abdominal drainage should be performed in such patients.
      Vascular inflow occlusion is recommended for all liver resections.

PMID- 1998470
TI  - Wither, whether, or whither surgical oncology.

PMID- 1998468
TI  - Why surgeons prefer not to care for trauma patients.
AB  - A survey of the Washington State Chapter of the American College of Surgeons was
      undertaken to document the opinions of surgeons on trauma care issues. Thirty
      nine percent of the total sample of surgeons who responded would prefer not to
      treat any trauma patients. These surgeons were more likely to be older, to
      practice in an urban setting, to feel that trauma call has a negative impact on
      elective practice, and to believe more strongly that reimbursement from trauma
      patients is not equal to that of nontrauma patients. They also agreed more
      strongly with the statements that these patients require a greater time
      commitment and pose an increased medicolegal risk. The most significant influence
      on preference not to treat trauma patients was exerted by the perception of a
      negative impact on practice, older age, and perception of increased medicolegal
      risk. Reimbursement issues and location of practice were less influential
      factors. This information can be used to target concerns and barriers to active,
      willing participation in a trauma care system and to tailor strategies to deal
      with them effectively.

PMID- 1998471
TI  - Inflammatory breast cancer.
AB  - Historically, the prognosis of inflammatory breast cancer has been poor. We
      conducted a retrospective review to evaluate the recent Memorial Sloan-Kettering
      Cancer Center experience, to evaluate the role of combination chemotherapy, and
      to compare the effect of surgery and radiation on local/regional failure. Fifty
      six patients with local/regional inflammatory breast cancer diagnosed between
      1975 and 1984 were identified. All were treated with combination chemotherapy.
      Overall 5-year survival was 45% with a 5-year disease-free survival rate of 37%.
      Twenty-one patients were treated with induction chemotherapy followed by
      mastectomy and adjuvant chemotherapy. Survival and disease-free survival rates
      were similar to those achieved in patients treated with mastectomy followed by
      chemotherapy. Residual cancer was found in all 21 patients treated with induction
      chemotherapy, with extensive disease present in 18, including six of seven
      complete responders. The local/regional failure rate was 34%.

PMID- 1998472
TI  - Enhanced antitumor reactivity of tumor-sensitized T cells by interferon alfa.
AB  - Tumor-draining lymph node cells from mice bearing the methylcholanthrene-induced
      MCA 106 tumors can be sensitized in vitro to acquire antitumor reactivity. We
      examined the effect of interferon alfa on the function of cells that underwent in
      vitro sensitization in adoptive immunotherapy. Interferon alfa increased the
      antitumor reactivity of in vitro sensitized cells in the treatment of MCA 106
      pulmonary metastases. This effect was evident in irradiated mice, indicating that
      a host response to the interferon alfa was not required. Interferon alfa
      treatment increased class I major histocompatibility complex antigen expression
      on tumor cells and increased their susceptibility to lysis by in vitro sensitized
      cells. These results suggest that interferon alfa enhancement of adoptive
      immunotherapy was mediated by its effect on tumor cells. Interferon alfa may be a
      useful adjunct to the adoptive immunotherapy of human cancer.

PMID- 1998473
TI  - Prognostic significance of carcinoembryonic antigen in colorectal carcinoma.
      Serum levels before and after resection and before recurrence.
AB  - The use of carcinoembryonic antigen was evaluated in 425 patients with a mean
      follow-up of 48 months. The preoperative and postoperative carcinoembryonic
      antigen levels were predictive of recurrence and survival independent of the
      tumor stage. In a multivariate regression analysis of age, location, tumor stage,
      and preoperative and postoperative carcinoembryonic antigen levels, the latter
      three factors were significant prognostic variables with respect to the adjusted
      survival. Recurrent disease was found in 42% of patients, excluding patients with
      stage IV disease. The carcinoembryonic antigen level at recurrence was greater
      than 5 ng/mL in 79% of the patients and in 89% of the intra-abdominal
      recurrences. Carcinoembryonic antigen level at recurrence was not predictive of
      postrecurrence survival except in the subgroup of locoregional disease. The life
      span in patients with liver and lung metastases was not influenced by
      carcinoembryonic antigen level at recurrence. Preoperative and postoperative
      carcinoembryonic antigen levels can indicate a poorer prognostic group of
      patients with colorectal cancer who may benefit from adjuvant treatment. The
      carcinoembryonic antigen at recurrence can be used effectively to diagnose intra
      abdominal recurrences and project survival after development of local/regional
      disease.

PMID- 1998474
TI  - Technique of photodynamic therapy for disseminated intraperitoneal malignant
      neoplasms. Phase I study.
AB  - Patients with disseminated intraperitoneal malignant neoplasms were given intra
      abdominal photodynamic therapy. Patients received dihematoporphyrin ethers
      intravenously 48 to 72 hours before laparotomy at doses of 1.5 to 3.0 mg/kg. At
      operation, as much tumor as possible was resected. Red light (630 nm) was
      delivered to all peritoneal surfaces from an argon-pumped dye laser at doses
      ranging from 0.2 to 3.0 J/cm2 in an escalating fashion. Viscera and peritoneal
      surfaces were anatomically isolated and exposed to light for intervals calculated
      to deliver the prescribed energy. Light was delivered to mesentery and bowel by a
      flat-cut optical fiber, while other areas, including diaphragm, viscera, omental
      bursa, gutters, and pelvis, were delivered light through a diffusing wand. Twenty
      three patients (13 with ovarian cancer, eight with sarcoma, and two with
      pseudomyxoma peritoneii) underwent photodynamic therapy. Five of eight patients
      cleared positive peritoneal cytologies after treatment. Six patients remained
      clinically free of disease for up to 18 months, and five patients had treatment
      related complications. Intraperitoneal phototherapy is technically feasible and
      deserving of clinical evaluation.

PMID- 1998475
TI  - Prognostic factors in primary retroperitoneal soft-tissue sarcomas.
AB  - We analyzed independent treatment variables (age, sex, signs and symptoms, site,
      size, histopathologic findings, grade, and clinical presentation) and treatment
      dependent variables (resectability, type of operation, surgical margins, surgical
      boundaries, microscopic margins, adjuvant radiotherapy, and adjuvant
      chemotherapy) in 80 patients with primary retroperitoneal soft-tissue sarcomas
      admitted from 1982 through 1988. Both univariate and multivariate analysis of
      survival and disease-free survival were performed. The major factor in survival
      outcome was the ability to completely resect the lesion. When the 62 patients who
      underwent complete resection were examined, the only independent prognostic
      factor for both survival and disease-free survival was grade. We conclude that
      completeness of resection and grade of the lesion are primary determinants of
      survival. Once all tumor is macroscopically removed, no advantage could be
      demonstrated by more extensive surgical resection or current adjuvant therapy.

PMID- 1998476
TI  - An approach to the reduction of the most common Western cancers. The failure of
      therapy to reduce disease.

PMID- 1998477
TI  - Radioimmunoguided surgery using iodine 125 B72.3 in patients with colorectal
      cancer.
AB  - Preliminary data using B72.3 murine monoclonal antibody labeled with iodine 125
      suggested that both clinically apparent as well as occult sites of colorectal
      cancer could be identified intraoperatively using a hand-held gamma detecting
      probe. We report the preliminary data of a multicenter trial of this approach in
      patients with primary or recurrent colorectal cancer. One hundred four patients
      with primary, suspected, or known recurrent colorectal cancer received an
      intravenous infusion of 1 mg of B72.3 monoclonal antibody radiolabeled with 7.4 x
      10 Bq of iodine 125. Twenty-six patients with primary colorectal cancer and 72
      patients with recurrent colorectal cancer were examined. Using the gamma
      detecting probe, 78% of the patients had localization of the antibody in their
      tumor; this included 75% of primary tumor sites and 63% of all recurrent tumor
      sites; 9.2% of all tumor sites identified represented occult sites detected only
      with the gamma detecting probe. The overall sensitivity was 77% and a predictive
      value of a positive detection was 78%. A total of 30 occult sites in 26 patients
      were identified. In patients with recurrent cancer, the antibody study provided
      unique data that precluded resection in 10 patients, and in another eight
      patients it extended the potentially curative procedure.

PMID- 1998478
TI  - Radical resection for carcinoma of the ampulla of Vater.
AB  - One hundred four consecutive patients who underwent radical resection for
      ampullary cancer between 1965 and 1989 were retrospectively reviewed. Frequent
      clinical findings included jaundice (67%), significant (greater than 10%) weight
      loss (42%), and anemia (27%). Eighty-seven patients (84%) underwent a subtotal
      pancreatectomy, and 17 patients (16%) underwent a total pancreatectomy. The
      postoperative mortality was 5.7% (six patients), and reoperation for
      postoperative complications was required in six patients. The 5- and 10-year
      survival rates were 34% and 25%, respectively. Eight patients died of tumor
      recurrence more than 5 years after resection. Patient survival was significantly
      impaired by microscopic lymphatic invasion, regional nodal metastasis, tumor
      grade, and the epithelium of origin. In a multivariate analysis, only microscopic
      lymphatic invasion significantly reduced patient survival. Radical resection for
      ampullary cancer can be performed with a low morbidity and mortality and should
      remain the procedure of choice for ampullary carcinoma.

PMID- 1998479
TI  - Effect of splenectomy on morbidity and survival following curative gastrectomy
      for carcinoma.
AB  - We performed a retrospective analysis of 392 patients who underwent curative
      resection of gastric adenocarcinoma to evaluate the impact of splenectomy on
      survival from gastric cancer and postoperative morbidity. Twelve factors,
      including splenectomy, were associated with a poor prognosis by univariate
      analysis. Multivariate analysis identified six of these factors, but not
      splenectomy, as independently predictive of death due to gastric cancer. The
      apparent adverse effect of splenectomy was due to its association with other
      significant risk factors. Postoperative complications occurred more commonly in
      patients who underwent splenectomy than in those who did not (45% vs 21%);
      patients in the splenectomy group also had a higher percentage of infectious
      complications than those in the nonsplenectomy group (75% vs 47%). We conclude
      that splenectomy has no direct influence on survival, but that it increases the
      morbidity of curative gastrectomy and should be avoided unless the spleen is
      close to or invaded by the tumor.

PMID- 1998480
TI  - Some problems with clinical trials. James Ewing lecture.

PMID- 1998481
TI  - History of liver surgery.
AB  - Although battle surgeons had debrided small bits of liver protruding through
      wounds since ancient times, formal entry into the peritoneal cavity to staunch
      hemorrhage due to trauma or to remove tumors or drain cysts had to await the
      advent of general anesthesia and antisepsis. After a burst of pioneering activity
      from 1880 to 1910, little progress was made until after World War II. In the last
      40 years, remarkable advances have been made in the techniques of liver
      resection, our understanding of liver diseases requiring operation, and our
      ability to support patients through major resections. Liver transplantation
      epitomizes the challenges that can now be accepted, and its success augurs well
      for an increase in liver operations in the future.

PMID- 1998482
TI  - Bilateral iliac vein filtration. An effective alternative to caval filtration in
      patients with megacava.
AB  - Greenfield filters were placed bilaterally in the iliac veins in five of 250
      patients undergoing percutaneous filter placements. Four of the five patients had
      megacava (inferior vena cava diameter greater than 28 mm). In all patients, the
      filters were effective in preventing pulmonary embolism. Follow-up at 9 months in
      two patients revealed no changes of chronic venous insufficiency or venous
      stasis. Iliac filtration should be considered in patients in whom a caval filter
      cannot be placed because of large caval size or because it is technically
      difficult due to iliac vein tortuosity.

PMID- 1998483
TI  - Cytologic diagnosis of aspergillosis in cardiac transplantation.
AB  - Fine-needle aspiration of the lung is now widely utilized to diagnose pulmonary
      neoplasms, but often serologic techniques or open-lung biopsy is relied on for
      the diagnosis of infectious pulmonary processes. We report a series of four
      patients in whom the fine-needle aspiration technique was used to make the rapid
      cytologic diagnosis of pulmonary aspergillosis. Culture confirmation was also
      obtained on the aspirated material. A discussion of the available techniques for
      the laboratory diagnosis of pulmonary aspergillosis is presented and the
      advantages of fine-needle aspiration cytology are stressed. Our favorable results
      support expanded use of fine-needle aspiration cytology in the evaluation of lung
      nodules appearing in immunosuppressed populations.

PMID- 1998484
TI  - Who should care for the SICU patient?

PMID- 1998485
TI  - What is blood compatibility?

PMID- 1998486
TI  - The effect of high pressure on microporous membrane oxygenator failure.
AB  - A retrospective study to determine the relationship between early microporous
      membrane oxygenator (MMO) failure and blood pressure at the MMO outlet (Pmo) was
      conducted using data collected with 19 dogs (22 +/- 1 kg, mean +/- SEM)
      undergoing routine normothermic cardiopulmonary bypass. Because gas flow was
      maintained at a high level, it could not be used to control CO2 exchange.
      Instead, blood PCO2 was controlled by adding CO2 to the sweep gas. Blood PO2 was
      controlled as suggested by the manufacturer, by adjusting the %O2 in the gas
      phase (g). Blood flow was 2575 +/- 54 ml/min; Pmo ranged from 173 to 790 mm Hg;
      and hematocrit was 33 +/- 1%. O2 exchange was calculated from blood gas
      parameters. Changes in the diffusion potential of O2 (delta PO2) and CO2 (delta
      PCO2) and MMO performance (P, taken as oxygen exchange normalized to a diffusion
      potential of 100 mm Hg) indicated MMO failure. Initial values, taken within 60
      min of bypass initiation, were compared to final values taken at 226 +/- 9 min of
      bypass. Despite higher final delta PO2 (411 +/- 9 vs. 538 +/- 19 mm Hg, p less
      than 0.0001 paired t-test) and delta PCO2 (18.6 +/- 2.4 vs. 30.5 +/- 4.7 mm Hg, p
      less than 0.0017), arterial blood PO2 decreased (159 +/- 15 to 89 +/- 6 mm Hg, p
      less than 0.0005) and PCO2 increased (36.4 +/- 1.5 to 46.1 +/- 3.0 mm Hg, p less
      than 0.0039), and the performance decreased [24.5 +/- 1.1 to 20.1 +/- 0.7
      (ml/min)/(100 mm Hg), p less than 0.0001].(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1998487
TI  - Effect of extracorporeal membrane oxygenation on leukocyte function in neonates.
AB  - The impact of extracorporeal membrane oxygenation (ECMO) on neonatal leukocyte
      content and function was examined in six patients. Patients were treated with
      ECMO for a mean of 134 h (range 44-246 h). Absolute neutrophil counts decreased
      from 14679 +/- 2291/mm3 to 7791 +/- 1672/mm3 after 2 h of ECMO. However,
      neutrophil phagocytosis and oxidative burst remained unchanged during the first
      48 h of bypass. Monocyte counts also decreased during bypass, and at times were
      undetectable in 50% of patients. Monocyte HLA-DR content was decreased compared
      to normal cord blood prior to initiation of ECMO, and remained low throughout
      ECMO. However, the content increased significantly after termination of bypass.
      Plasma C3a levels increased transiently, paralleled by an increase in neutrophil
      CR3 expression. While moribund infants had some impairment of host defenses prior
      to ECMO, there was no further impact of ECMO per se on the parameters measured,
      other than transient complement activation and decreased monocyte counts.

PMID- 1998488
TI  - Characterization of rehydrated gelatin gels.
AB  - Five percent glutaraldehyde cross-linked gels have shown excellent blood
      compatibility as coatings for cardiac prostheses. A method was developed for
      producing thin dehydrated coatings using a proprietary dehydration procedure and
      ethylene oxide (EO) sterilization. The swollen surfaces of rehydrates versus wet
      (original) gels were compared. Within 30 min of saline rehydration, dry 30-50
      microns films on textured surfaces became smooth, uniform, and comparable to
      original gelatin gels. Mechanical test results after rehydration showed values
      for strain remain unchanged (39.3 + 10.0 to 40.0 + 7.8%), but stress increased
      (2.79 + 1.21 to 4.22 + 1.60 dyne/cm2; p less than 0.01). The contact angle data
      reported gamma C values of 26.1 and 30.4 dyne/cm for original and rehydrated
      gels. Using a coulometric titrimeter, the measured water content of original gels
      was reduced from 85 to 3.4% after drying. Dried and saline rehydrated gels had a
      73.2% moisture content. Gels shrank 8.8% of their original length after
      rehydration; however, the thickness of all pump coatings remained stable. Two
      hour incubations with bovine platelet rich plasma showed no differences in
      platelet reactivity or morphology when compared to original gels. Light
      microscopy and scanning electron microscopy (SEM) showed no evidence of gel
      cracking or surface defects after pump endurance testing for 3 and 5 weeks. The
      process of dehydration eliminates the wet storage and sterility problems of such
      hydrogels and provides a stable film coating for a variety of blood-contacting
      substrates.

PMID- 1998489
TI  - Comparison of a steady flow pump to a preload responsive pulsatile pump in left
      atrial-to-aorta bypass in canines.
AB  - A unique preload responsive pulsatile pump was compared to a centrifugal pump in
      total cardiac support in 25-kg canines (n = 6, each group) in the left atrial-to
      aorta mode during 5 h of ventricular fibrillation. With steady flow, there was
      immediate drop in output from 2.1 +/- 1.0 L/min to 1.4 +/- 0.3 L/min, followed by
      further reduction to 0.9 +/- 0.2 L/min during 5 h of ventricular fibrillation.
      With a pulsatile pump, there was no significant reduction from control of 2.4 +/-
      0.6 L/min and no decline during 5 h of ventricular fibrillation. With steady
      flow, systemic vascular resistance (SVR) rose significantly from 1,762 dyne-s-cm
      5 immediately on pump to 3,013 dyne-s-cm-5 at 5 h. With physiologic pulsatile
      flow, significant elevation of SVR did not occur. When stressed, due to
      diminished left atrial return, the centrifugal pump displayed line chatter and
      streaks of microbubbles, whereas the pulsatile pump did not. Crystalloid volume
      replacement with the centrifugal pump was 6.5 +/- 1.9 L, and with the preload
      responsive pulsatile pump, 5.6 +/- 1.3 L. It is concluded that in the left atrial
      to-aorta mode during 5 h of ventricular fibrillation and with comparable volume
      replacement, total cardiac support of canines is associated with lower SVR with
      physiologic pulsatile flow and is not accompanied by line chatter and cavitation
      with this preload responsive pump.

PMID- 1998490
TI  - Myointimal hyperplasia: pathogenesis and implications. 1. In vitro
      characteristics.
AB  - Myointimal hyperplasia (MIH) is an arterial wall smooth muscle cell (SMC)
      proliferative disorder. This process is responsible for a significant number of
      early and long-term arterial reconstructive and graft failures.
      Histopathologically, this process is characterized by a proliferation of SMC in
      the intima of traumatized arteries resulting in arterial and/or anastomatic
      stenosis with secondary thrombosis. In vitro studies of cultured SMC have allowed
      the evaluation of SMC response to factors suspected of being clinically
      associated with MIH. Principal among these is platelet derived growth factor
      (PDGF), which is known to be secreted by several cell types including endothelial
      cells (ECs) and monocytes as well as being stored and secreted by platelets.
      PDGF, somatomedin-C, epithelial growth factor, insulin, and other factors have
      been found to significantly increase SMC replication in vitro. Lipoproteins may
      be important substrates for SMC proliferation in contrast to heparin, which may
      directly inhibit SMC protein synthesis. Unlike SMCs, whose continued growth in
      culture is dependent on various growth factors and nutrients, ECs essentially
      cease to proliferate after the cells have formed a monolayer over the available
      surface. Extracellular matrix proteins, polypeptide mitogens, and heparin have
      been shown to modify EC migration and proliferation in vitro. Wounding of EC
      monolayers by scratching results in increased replication and migration,
      processes which require plasma factors that remain poorly defined. However, two
      general forms of EC growth factor have been isolated from many body tissues, are
      potent stimulators of capillary endothelial growth, and appear important both for
      normal EC monolayer homeostasis and for the response to injury. Cultured ECs
      produce mitogens for SMC. Production of the principal mitogen, PDGF, is
      significantly increased in sparse versus confluent cell cultures as well as by
      toxic agents such as endotoxin and phorbol esters. Acetyl low density lipoprotein
      as well as omega-3 fatty acids may significantly and selectively inhibit EC PDGF
      production, a finding with potentially profound implications for the clinical
      control of MIH in vivo.

PMID- 1998492
TI  - Development of a compact extracorporeal membrane oxygenation (ECMO) system.
AB  - In recent years, extracorporeal membrane oxygenation (ECMO) has been used for
      treatment of neonates with respiratory failure. A prototype of a compact ECMO
      system for neonates was developed. A single-lumen catheter, inserted into the
      right atrium via a jugular vein, was used for withdrawal and infusion of blood
      through the catheter. An extracapillary flow hollow-fiber membrane lung made of
      microporous polypropylene has a total surface area of 0.6 m2. To prevent the
      increase of plasma free hemoglobin, the ratio of withdrawal/infusion is
      controlled by a microcomputer. The system is compact in size with a low priming
      volume (less than 90 ml), which allows for ECMO with no additional blood
      transfusions. Its potential application as a respiratory support system is
      evaluated in animal experiments. The total intermittent veno-veno bypass flow was
      15-30 ml/min/kg. The O2 transfer rate was 20 ml/min and the CO2 transfer rate was
      33 ml/min at a blood flow rate of 300 ml/min. The O2 and CO2 exchange with the
      ECMO system was efficient enough to eliminate the respiratory failure induced by
      mechanical ventilation. The increase in plasma free hemoglobin was only 4 mg/dl
      after 6 h of ECMO. The system was considered applicable to respiratory aid for
      neonates.

PMID- 1998491
TI  - Vascular responsiveness to various vasoactive substances after exchange
      transfusion with pyridoxalated hemoglobin polyoxyethylene conjugate (PHP)
      solution in anesthetized rats.
AB  - Vascular responsiveness to various vasoactive substances after exchange
      transfusion with a modified hemoglobin (pyridoxalated hemoglobin polyxyethylene
      conjugate; PHP) was examined in anesthetized rats. The hindlimb region of the rat
      was perfused through the abdominal aorta with autologous blood at a constant flow
      rate, using a perfusion pump. Perfusion pressure (PP), systemic blood pressure
      (SBP), and heart rate were measured. Exchange transfusion with a 6% PHP solution
      (20 ml/kg) was performed and effects of intra-arterial injections of
      norepinephrine (NE), angiotensin-II (A-II), serotonin (5-HT), acetylcholine
      (ACh), and nitroglycerin (NG) on PP and SBP were examined. The NE and A-II
      induced a dose-dependent increase in PP, while ACh and NG induced a decrease in
      PP. There was no difference in vascular responsiveness to ACh, NG, A-II, and 5-HT
      before and after exchange transfusion with PHP solution, but NE-induced responses
      were augmented after exchange transfusion with PHP. Results suggest that the
      presence of PHP moiety in circulation would not alter vascular responsiveness to
      ACh, NG, A-II, and 5-HT in a significant manner.

PMID- 1998494
TI  - An overview of neural networks.
AB  - Some of the world's leading researchers in neural networks submitted their most
      recent results concerning their research in neural networks to the author for
      inclusion in this survey. Descriptive accounts of their collective papers are
      presented as well as a list of sources of information concerning neural networks,
      such as journals, books, and technical reports. The material is broken into
      categories related to established areas in computer science, robotics, neural
      modeling, and engineering.

PMID- 1998493
TI  - Hemostatic alterations caused by ventricular assist devices for postcardiotomy
      heart failure.
AB  - The hemostatic alterations in two adult patients who were supported by left
      ventricular assist devices (LVADs) because of postcardiotomy heart failure were
      evaluated. In both patients, fibrinopeptide A and thrombin-antithrombin III
      complex increased markedly during the first several days, and thereafter
      decreased moderately but remained above normal over the entire procedure.
      Furthermore, fibrinopeptide B beta 15-42 and alpha 2 plasmin inhibitor-plasmin
      complex were also markedly increased over the entire course of LVAD treatment.
      These data show that the LVAD system strongly activates both the coagulation and
      the fibrinolytic system, even when thromboembolic or bleeding complications are
      not clinically evident. Furthermore, the decrease in physiological coagulation
      inhibitors, especially protein C, indicates that these factors are activated and
      consumed during LVAD treatment. Because protein C is important in regulating the
      coagulation cascade during LVAD treatment, exhaustion of this system might result
      in thromboembolic complications during LVAD treatment.

PMID- 1998495
TI  - Inhibition of infection with human immunodeficiency virus type 1 by sulfated
      gangliosides.
AB  - Four kinds of gangliosides, namely GM1a, GD1a, GD1b and GT1b and their sulfated
      derivatives were examined for antiviral activities against human immunodeficiency
      virus type 1 and abilities to modulate CD4 antigen on the cell surface. The
      infection of human T cells with the virus was markedly inhibited by treatment
      with the sulfated gangliosides at a concentration of 10 micrograms/ml, while the
      non-sulfated gangliosides had only weak antiviral activities. The sulfated
      gangliosides completely inhibited syncytium formation induced by HIV-1 at 30
      micrograms/ml. The CD4 antigen on the surface of T cells became hardly detectable
      after treatment with them. They did not damage cells, nor prolong the activated
      partial thromboplastin time at concentrations of up to 100 micrograms/ml,
      suggesting that they may have little side effect in vivo.

PMID- 1998496
TI  - Cloning and nucleotide sequence of a bovine pancreatic preprocarboxypeptidase A
      cDNA.
AB  - A full-length cDNA clone encoding bovine pancreatic preprocarboxypeptidase A was
      isolated and sequenced. The 1405-base pair insert contains a 26-nucleotide 5'
      noncoding region, a 1260-nucleotide open reading frame and a 76-nucleotide 3'
      noncoding fragment plus a poly(A) tail of at least 43 nucleotides. The open
      reading frame encodes a protein of 419 amino acids, including the 16 amino acid
      signal peptide. The mature enzyme (309 residues) has two additional C-terminal
      amino acids, as compared with the amino acid sequence of the protein which was
      reported more than 20 years ago. In addition, four residues deduced from the
      nucleotide sequence differed from those identified in the reported amino acid
      sequence from their net charge: Asp-89, Asp-114, Gln-122, and Asp-185 instead of
      Asn-89, Asn-114, Glu-122, and Asn-185, respectively. A high degree of identity
      exists between the nucleotide sequences (81.3%), on the one hand, and the amino
      acid sequences (78.3%), on the other hand, of bovine preprocarboxypeptidase A and
      rat preprocarboxypeptidase A1.

PMID- 1998497
TI  - Comparison of the estrogen responsiveness of the rat and bovine oxytocin gene
      promoters.
AB  - DNA sequences in the 5'-flanking region of rat and bovine oxytocin genes were
      examined for their capacity to confer estrogen responsiveness to their homologous
      promoters. In contrast to the 5'-flanking region of the rat oxytocin gene,
      upstream promoter sequences up to 3200 bp of the bovine gene linked to the
      chloramphenicol acetyltransferase (CAT) reporter gene which were transfected in
      estrogen receptor expressing MCF-7 cells did not respond to estrogen. Testing 5'
      deletion mutants of the rat upstream region linked to the luciferase gene in P19
      embryocarcinoma cells co-transfected with an estrogen receptor expression plasmid
      showed that two regions each associated with approximately 15-fold stimulation of
      promoter activity were located between nucleotides -172 and -149 and between -148
      and +16 in the rat gene. The former region contains the imperfect palindrome
      GGTGACCTTGACC which differs in one nucleotide from the estrogen response element
      (ERE) consensus. It is concluded that the corresponding motive CATAACCTTGACC of
      the bovine gene is not a functional ERE. Thus, the estrogen responsiveness of
      oxytocin genes is species-dependent.

PMID- 1998498
TI  - Identification of a thioredoxin-related protein associated with plasma membranes.
AB  - A low molecular weight membrane associated sulphydryl protein was detected on a
      wide range of nucleated cells when [14C]-iodoacetamide was used as a probe. This
      protein was extracted from THP-1 monocytes, purified to homogeneity and its
      isoelectric point, Mr and N-terminal amino acid sequence determined. These were
      shown to be almost identical to the corresponding values for both human
      thioredoxin and a Tac interleukin-2 receptor activator, indicating that the
      protein may be a member of this family and function as an essential growth
      factor.

PMID- 1998499
TI  - Diminished phosphorylation of a heat shock protein (HSP 27) in infant acute
      lymphoblastic leukemia.
AB  - We have previously reported lack of expression of a polypeptide designated L3 in
      infant acute lymphoblastic leukemia (ALL). Expression of L3 occurred
      predominantly in older children with pre-B ALL. We have recently reported the
      expression during B cell ontogeny of two other polypeptides, designated L2 and L4
      with a similar Mr as L3, which were identified as phosphorylated and non
      phosphorylated forms respectively of the low Mr heat shock protein. hsp27. In
      this study we have characterized L3 and identified it as another phosphorylated
      form of hsp27. The two phosphorylated forms appear to be differentially expressed
      in acute leukemia. L3 levels in infants who expressed hsp27 isoforms L2 and L4
      were significantly diminished compared to levels in older children with an
      equivalent amount of hsp27. We conclude that leukemic cells in infant ALL exhibit
      a unique pattern of phosphorylation of hsp27 expressed at a pre-B cell stage of
      differentiation.

PMID- 1998500
TI  - Autocatalytic processing of procathepsin E to cathepsin E and their structural
      differences.
AB  - The processing of human gastric procathepsin E to its mature form, cathepsin E,
      was studied at pH 3.5. The results revealed the autocatalytic and apparently one
      step conversion of procathepsin E to cathepsin E within 10 min of incubation at
      14 degrees C under the conditions used. Analyses of the amino acid sequences of
      both procathepsin E and cathepsin E showed that cleavage occurred at the Met36
      Ile37 bond to produce the mature form, cathepsin E. The NH2-terminal amino acid
      sequence of procathepsin E thus determined was identical with that predicted from
      the cDNA sequence by Azuma et al. except that the NH2-terminal glutamine residue
      in the latter was converted into a pyroglutamic acid residue in the former and
      that the glycine residue at position 2 in the latter sequence was deleted in the
      former. On the other hand, the NH2-terminal amino acid sequence of cathepsin E
      was identical with that reported previously by us.

PMID- 1998501
TI  - Antigen-induced phospholipase D activation in rat mast cells is independent of
      protein kinase C.
AB  - In the present study, we investigated the involvement of protein kinase C (PKC)
      in antigen (Ag, DNP-Ascaris suum)-induced phospholipase D (PLD) activation of rat
      peritoneal mast cells. Phorbor myristate acetate (PMA) as well as Ag activated
      PLD as inferred by phosphatidylethanol (PEt) production. PKC inhibitors,
      staurosporine and H-7, however, failed to suppress PMA-stimulated PLD activation,
      suggesting that PLD activation by PMA is independent of PKC. By contrast, Ag
      stimulated PLD activity was significantly reduced by staurosporine and slightly
      by H-7. Surprisingly, the inhibitors inhibited Ag-stimulated phospholipase C
      (PLC), correlated to the inhibition of PLD. These observations lead us to
      conclude that in Ag-stimulated mast cells 1,2-diacylglycerol (DG) formed by PLC
      directly or indirectly stimulates PLD, independently of PKC.

PMID- 1998502
TI  - A novel detection of a single Plasmodium falciparum in infected blood.
AB  - Detection of Plasmodium falciparum malaria by a specific DNA probe is a highly
      promising means for epidemiological surveillance of human malaria. However, none
      of presently available DNA probe methods could detect as little as a few
      parasites in infected blood. By amplification of a specific 206 base pairs P.
      falciparum DNA sequence using the polymerase chain reaction (PCR), as little as
      0.01 picogram DNA or one-half of a parasite was sufficient for a specific
      detection. A PCR procedure for detection of P. falciparum in infected blood
      without prior DNA extraction was also developed which was sensitive for a single
      parasite. The procedure was simple and should be applicable for a large scale
      epidemiological study involving a very low parasitemia situation.

PMID- 1998503
TI  - Structure and chromosome assignment of human S100 alpha and beta subunit genes.
AB  - The human S-100 alpha and beta subunit genes were isolated from human genomic DNA
      library. The restriction endonuclease mapping and DNA sequencing analysis
      revealed that both subunit genes consisted of three exons and two introns. Two
      Ca2(+)-binding domains were independently encoded by exon 2 and exon 3. Spot-blot
      hybridization analysis with flow-sorted chromosomes showed that human alpha and
      beta subunit genes were assigned to chromosome 1 and chromosome 21, respectively.

PMID- 1998504
TI  - Antisense sequences of antigenic peptides are found in MHC class II molecules.
AB  - The sequence of the well known antigenic peptide OVA 323-339 as well as other
      peptides containing reiterative motifs of the core region essential for binding
      to Class II MHC molecules was compared for homology with the DNA derived
      antisense peptide sequences corresponding to the alpha chain of the mouse IAd
      molecule. Homology was obtained within the sequence found in the transmembrane
      region of the molecule. Increased binding of the peptides containing the
      reiterative motifs based on the OVA 323-339 sequence may be due to the increased
      number of contact sites on IAd molecules which were identified as being
      complementary in a sense-antisense manner.

PMID- 1998505
TI  - Memory impairment and morphological changes in rats induced by active fragment of
      anti-nerve growth factor-antibody.
AB  - Treatment of rats with a specific Fab' fragment of anti-nerve growth factor (NGF)
      antibody (anti-NGF, 12, 120 and 400 micrograms/4 weeks, i.c.v.) impaired their
      learning ability. The distance of swimming of anti-NGF-treated rats in a water
      maze was shortened more slowly by training than that of control rats. Anti-NGF
      treatment altered the staining of nuclei of cells in the hippocampus, parietal
      cortex and dentate gyrus with hematoxylin. It is suggested that the anti-NGF
      induced amnesia could be due to change in nuclear morphology.

PMID- 1998506
TI  - Degradation of brain natriuretic peptide by neutral endopeptidase: species
      specific sites of proteolysis determined by mass spectrometry.
AB  - Brain natriuretic peptide (BNP) from 3 different species was cleaved by neutral
      endopeptidase (NEP) and the products separated by HPLC. The newly formed products
      were identified by fast atom bombardment or nebulizer-assisted electrospray mass
      spectrometry to elucidate the sites of proteolysis. Porcine BNP was cleaved at
      the Arg8-Leu9 and Ser14-Leu15 bonds. Rat BNP was cleaved at the Arg23-Leu24 and
      Arg30-Leu31 bonds. Human BNP was cleaved at the Pro2-Lys3, Met4-Val5 and Arg17
      Leu18 bonds. The Cys-Phe bond which is present in all species of BNP is not
      cleaved by NEP.

PMID- 1998507
TI  - A sensitive enzyme immunoassay for human basic fibroblast growth factor.
AB  - A sensitive sandwich enzyme immunoassay for human basic fibroblast growth factor
      (HbFGF) was developed employing three monoclonal antibodies (MAb3H3, MAb98 and
      MAb52). The Fab' fragment of MAb3H3 which inhibits HbFGF biological activity was
      conjugated to horseradish peroxidase. A mixture of MAb52 and MAb98 was used in
      the solid phase. Neither human acidic fibroblast growth factor, hst-1/KS3 product
      nor acid denatured HbFGF was cross-reactive in this assay system. The detection
      limit of this assay system was 1 pg/well. Using this assay, some tumor cell lines
      were revealed to produce a higher level of bFGF than a normal one. Serum samples
      from normal volunteers were also assayed, and immuno-reactive HbFGF could be
      detected in 16 out of 57 samples at range 30 approximately 206 pg/ml.

PMID- 1998508
TI  - Granulocyte phospholipase D is activated by a guanine nucleotide dependent
      protein factor.
AB  - When post-nuclear homogenates from HL-60 granulocytes are incubated in the
      presence of CaCl2, GTP gamma S and ethanol, phospholipase D (PLD) metabolizes
      both exogenous 2-[14C]arachidonyl-phosphatidylcholine and endogenous
      phosphatidyl[3H]choline to produce 2-[14C]arachidonyl-phosphatidic acid, 2
      [14C]arachidonyl-phosphatidylethanol and [3H]choline. Fractionation of the
      homogenate by ultracentrifugation into cytosolic and membrane fractions results
      in the loss of PLD activity. However, when these two fractions are combined in
      the same proportion as found in the unfractionated homogenate, PLD activity is
      completely restored. This activity is proportional to the concentration of both
      the cytosol and the particulate fractions. Release of [14C]arachidonate by PLA2
      that occurs under these assay conditions does not require the combined presence
      of cytosol and membrane fractions. We conclude that, in granulocyte homogenates,
      PLD activity but not arachidonate release, exhibits an essential requirement for
      a heat-labile factor whose activity depends on the presence of GTP gamma S.

PMID- 1998509
TI  - A unique cellular myosin II exhibiting differential expression in the cerebral
      cortex.
AB  - Clones possessing inserts of brain myosin II have been obtained by screening a
      rat brain cDNA expression library with a polyclonal antibody, raised against
      myosin II from the mouse neuroblastoma cell line, Neuro-2A. A partial sequence
      comprising the 3' coding and non-coding regions of the myosin message has been
      determined which is markedly different from other myosin sequences. The derived
      amino-acid sequence comprises the C-terminal 90 amino acids:
      VSS(PO4)LKNKLRRGDLPFVVTRRLVRKGTLELS(PO4)DDDDESKASLINETQPPQCLDQQ LDQQ
      LDQLFNWPVNAGCVCGWGVEQTQGEEAVHKCRT(CO2H). This sequence encompasses regions
      homologous to both the casein kinase II and protein kinase C heavy-chain
      phosphorylation sites. The non-helical "tail-piece" is considerably longer (an
      additional 39 amino acid residues) than found in other myosins. Northern blot
      analysis demonstrates this myosin II message to be unique to cerebral cortex,
      with no expression in all other non-cortical brain regions and peripheral tissues
      tested. Our results suggest functional diversity for myosin II isozymes within
      the brain.

PMID- 1998510
TI  - Halothane metabolism: Kupffer cells carry and partially process
      trifluoroacetylated protein adducts.
AB  - Kupffer cells, prepared 18 h after pretreatment of rats with a single dose of
      halothane, did carry TFA-adducts which were recognized on Western blots by a anti
      TFA-antibody. Based on apparent molecular weight, the pattern of the major TFA
      adducts within Kupffer cells was similar to that observed in hepatocytes. When
      kept in primary culture, Kupffer cells processed TFA-adducts of apparent
      molecular weight of 220 kD, 110 kD and 74 kD within 24 or 48 h; in contrast,
      other TFA-adducts were persistent for at least 48 h in Kupffer cells. The data
      suggest a role for Kupffer cells in processing of chemically altered proteins in
      the liver.

PMID- 1998511
TI  - CD36-mediated signal transduction in human monocytes by anti-CD36 antibodies but
      not by anti-thrombospondin antibodies recognizing cell membrane-bound
      thrombospondin.
AB  - Mononuclear cells (MNC) treated with anti-CD36 Fab or F(ab')2 fragments and then
      stimulated with anti-rabbit (F(ab')2 displayed an oxidative burst, suggesting
      that the crosslinking of CD36 promotes signal transduction in the absence of an
      Fc receptor involvement. Moreover, intact anti-TSP mediates a weak oxidative
      burst in MNC, which was strongly enhanced upon pretreatment of monocytes (but not
      lymphocytes) with TSP. This response, however, was mediated by Fc receptors, not
      by an involvement of CD36. Other means of crosslinking cell-bound TSP and
      exposure of MNC to surface-bound TSP failed to promote an oxidative burst.
      Crosscompetition tests confirmed that the interaction site(s) of TSP with
      monocytes are distinct from the signal-promoting sites recognized by polyclonal
      and 3 monoclonal anti-CD36 antibodies.

PMID- 1998512
TI  - Heterogeneity of smooth muscle myosin light chain kinase is revealed by anion
      exchange high-performance liquid chromatography.
AB  - When smooth muscle myosin light chain kinase, purified by standard procedures
      from chicken gizzard smooth muscle, was applied to an anion-exchange high
      performance liquid chromatographic column, three well resolved peaks were
      obtained. Each peak contained a single protein whose electrophoretic mobility
      corresponded to that of MLCK. However each enzyme was characterized by a
      different specific activity. Peptide mapping experiments were unable to
      demonstrate different proteolytic patterns for the three proteins. Treatment of
      myosin light chain kinase with alkaline phosphatase, prior to ion chromatography,
      resulted in a change of elution profile. These experiments suggest that myosin
      light chain kinase could exist in three forms characterized by a different degree
      of phosphorylation.

PMID- 1998513
TI  - Human thyroid hormone beta 1 receptor produced by recombinant baculovirus
      infected insect cells.
AB  - Thyroid hormone receptors are nuclear proteins which regulate transcription in a
      hormone dependent manner. The baculovirus expression system was used for the
      overexpression of the beta 1 isoform of the human thyroid hormone receptor. The
      baculovirus produced receptor binds tri-iodothyronine with high affinity, is
      specifically immunoprecipitated with a beta 1 specific antibody, and binds to DNA
      that contains a known thyroid hormone receptor recognition site. Large scale
      production and purification of baculovirus produced receptor will be useful for
      structure-function analyses and studies of transcriptional regulation.

PMID- 1998514
TI  - FMRF-amide and L-Arg-L-Phe increase blood pressure and heart rate in the
      anaesthetised rat by central stimulation of the sympathetic nervous system.
AB  - The neuropeptide FMRFamide (L-Phe-L-Met-L-Arg-L-Phe-NH2) increases mean arterial
      blood pressure (MABP) and heart rate (HR) in the anaesthetised rat at
      concentrations ranging from 10-1000 micrograms/kg. Here, we demonstrate that
      peptides containing L-arginyl-L-phenylalanine (L-Arg-L-Phe), the C-terminal
      sequence of FMRFamide, mimic its haemodynamic effects. L-Arg-L-Phe was
      approximately 4 fold more potent in increasing MABP and HR than FMRFamide. In 40
      different peptides investigated, the following order of potency of the effective
      compounds was established: L-Arg-L-Phe-L-Ala = L-Arg-L-Phe greater than FMRFamide
      greater than L-Met-L-Arg-L-Phe = L-Arg-L-Trp greater than L-Arg-L-Tyr greater
      than D-Arg-L-Phe = L-Arg-L-Phe-OMe greater than L-Arg-L-Leu = L-Arg-L-Ile greater
      than L-Lys-L-Phe greater than L-Arg-L-Met. L-Arg-L-Phe or FMRFamide did not cause
      any pressor response in pithed rats, indicating a central mechanism of action. In
      anaesthetised rats, intravenous injections of FMRFamide or L-Arg-L-Phe (100
      micrograms/kg) were associated with a 2-3 fold increase in plasma noradrenaline
      levels, whereas plasma adrenaline levels remained unchanged. Thus, L-Arg-L-Phe
      may represent the active principle of FMRFamide acting by a central mechanism
      involving the release of noradrenaline from sympathetic nerve terminals.

PMID- 1998516
TI  - Amino acid substitutions in the SP1 zinc finger domain alter the DNA binding
      affinity to cognate SP1 target site.
AB  - Non conserved amino acids, which are located in the postulated alpha-helical
      region of the third zinc finger in human transcription factor SP1, have been
      replaced by amino acids, which occur at the analogous zinc finger position in
      human protein Kox 15. This helical domain was mutated from SDHLSKH to SSHLIOH
      (SP1-M3). Aspartic acid (D), serine (S) and lysine (K) were substituted by serine
      (S), isoleucine (I) and glutamine (Q). The DNA binding of the mutated SP1-M3
      protein to the SP1 cognate target site GGG GCG GGG was significantly impaired,
      indicating that the amino acids, aspartic acid, serine and lysine play a pivotal
      role in DNA recognition. The mutated SP1 finger cannot imitate the function of
      the wild type SP1 finger in interacting with the cognate SP1 target site. This
      structure-function analysis indicates that the third SP1 zinc finger participates
      in sequence-specific DNA recognition. Thus, the affinity of zinc finger domains
      can be altered by substituting a limited number of amino acids. This observation
      is consistent with the notion that zinc finger domains are positioned in the
      major groove of the DNA and wrap around the DNA. Structure-function analysis of
      this kind might lead to the description of a zinc finger specific recognition
      code.

PMID- 1998515
TI  - Special considerations in the purification of the GM3 ganglioside-forming enzyme,
      CMP-sialic acid:lactosylceramide alpha 2-3 sialyltransferase (SAT-1): effects of
      protease inhibitors on rat hepatic SAT-1 activity.
AB  - Co-purification of an endogenous proteolytic activity has been proposed as the
      cause for the size heterogeneity of sialyltransferases. Reported herein are
      results on the effects of various protease inhibitors, sulfhydryl-reducing agents
      and antimicrobial agents on SAT-1 activity. Addition of protease inhibitors to
      immunoaffinity-purified rat liver SAT-1 dramatically affects its activity. All
      protease inhibitors examined, with the exception of PMSF, inhibited the purified
      enzyme. The most inhibitory were the cysteine (thiol) protease inhibitors. This
      effect is less spectacular when the effect of these inhibitors was studied on SAT
      1 activity in Golgi-enriched microsomes, although the inhibition was greatest by
      the cysteine protease inhibitors. One dramatic effect, found in both cases, was
      the apparent activation of SAT-1 activity in the presence of beta
      mercaptoethanol.

PMID- 1998517
TI  - A lysophosphatidic acid-binding cytosolic protein stimulates mitochondrial
      glycerophosphate acyltransferase.
AB  - Rat liver cytosolic fraction caused up to five fold stimulation of mitochondrial
      glycerophosphate acyltransferase apparently by removing the lysophosphatidic acid
      formed by the acyltransferase. When mitochondria were incubated with palmityl
      CoA, [2-3H]-sn-glycerol 3-phosphate and the cytosolic fraction and the
      supernatant fluid of the incubated mixture was passed through a Sephadex G-100
      column, labeled lysophosphatidic acid eluted in three peaks with Mrs (i) 60-70
      kDa, (ii) 10-20 kDa, and (iii) less than 5 kDa. Proteins, responsible for binding
      of lysophosphatidic acid in peaks (i) and (ii), were purified to near homogeneity
      as judged by electrophoretic analysis. The lysophosphatidic acid binding protein
      in peak (i) appears to be serum albumin and peak (iii) represents largely unbound
      lysophosphatidic acid. The 15 kDa protein, purified from peak (ii), bound
      lysophosphatidic acid, stimulated the acyltransferase and export of
      lysophosphatidic acid from mitochondria.

PMID- 1998518
TI  - Distinct C-terminal sequences of isozymes I and II of the human erythrocyte L
      isoaspartyl/D-aspartyl protein methyltransferase.
AB  - We have purified the more acidic major isozyme (II) of the human erythrocyte L
      isoaspartyl/D-aspartyl methyltransferase and compared its structure to that of
      the previously sequenced isozyme I. These isozymes are both monomers of 25,000
      molecular weight polypeptides and have similar enzymatic properties, but have
      isoelectric points that differ by one pH unit. Analysis of 16 tryptic peptides of
      isozyme II accounting for 89% of the sequence of isozyme I revealed no
      differences between these enzyme forms. However, analysis of a Staphylococcal V8
      protease C-terminal fragment revealed that the last two residues of these
      proteins differed. The Trp-Lys-COOH terminus of isozyme I is replaced by a Asp
      Asp-COOH terminus in isozyme II. Southern blot analysis of genomic DNA suggests
      that the human genome [corrected] may contain only a single gene encoding the
      enzyme. We propose that the distinct C-termini of isozymes I and II can arise
      from the generation of multiple mRNA's by alternative splicing.

PMID- 1998519
TI  - A transforming growth factor related to epidermal growth factor is expressed by
      fetal mouse salivary mesenchyme cells in culture.
AB  - Fetal mouse salivary mesenchyme cells secrete a protein with an apparent MW of 15
      Kd that is immunologically related to epidermal growth factor (EGF). Conditioned
      medium collected from these cells in culture stimulates the growth of primary
      mouse mammary epithelial cells cultured within collagen gels, competes for
      binding to EGF receptor sites on these mammary epithelial cells and stimulates
      the anchorage-independent growth of normal rat kidney fibroblast cells within
      soft agarose. Prior immunoprecipitation of salivary mesenchyme cell conditioned
      medium with anti-EGF antibodies effectively removes or attenuates all of these
      effects confirming that an EGF-like factor is involved in these responses.

PMID- 1998520
TI  - Ingestion of eicosapentaenoic acid-ethyl ester renders rabbit LDL less
      susceptible to Cu2(+)-catalyzed-oxidative modification.
AB  - The present study revealed that low density lipoprotein (LDL) obtained from
      rabbits fed highly purified eicosapentaenoic acid-ethyl ester (EPA-E) (EPA-LDL)
      was significantly less susceptible to oxidative modification catalyzed by Cu2+ as
      compared to LDL from rabbits fed a normal diet (control LDL). In a comparison of
      fatty acid composition of LDL, the contents of EPA and docosapentaenoic acid were
      significantly increased in EPA-LDL as compared to control LDL. The content of
      arachidonic acid (AA) was the same in both LDL groups. The contents of total
      cholesterol, free cholesterol, triglyceride, and phospholipid in LDL were
      unchanged by EPA-E ingestion. These data raise the possibility that EPA may
      protect LDL from oxidative modification, leading to a reduction of oxidized LDL
      in atherosclerotic lesions, and that this may be how EPA exert its anti
      atherosclerotic action.

PMID- 1998521
TI  - Specific binding of vascular permeability factor to endothelial cells.
AB  - Vascular permeability factor (VPF), also known as vascular endothelial cell
      growth factor, has recently been purified from guinea pig, human, and bovine
      sources. We show that various fetal or adult endothelial cell strains originating
      from either capillary or large vessels possess specific high affinity and
      saturable binding sites for guinea pig tumor-derived [125I]VPF. Two classes of
      sites with KDs of approximately 10 pM and 1 nM were detected for all endothelial
      cell types examined. Guinea pig [125I]VPF binding to endothelial cells was
      inhibited by human VPF (ID50 = 0.8 ng/ml) and by suramin (ID50 = 75
      micrograms/ml) but not by heparin. Cross-linking experiments revealed specific
      [125I]VPF-receptor complexes of two types. Most of the complexes migrated very
      slowing in SDS-PAGE, indicating that they were of very high molecular weight and
      probably highly cross-linked. A portion of the molecules migrated as 270 kDa
      complexes, indicating that the molecular weight of the endothelial cell VPF
      receptor is about 230 kDa.

PMID- 1998522
TI  - Modulation of B2 containing small RNAs during induced differentiation of murine
      erythroleukemia cells.
AB  - We identified a B2 repetitive element approximately 1.9kb down stream from mouse
      p53 coding gene. This element was then used as a probe to investigate the
      expression of B2 containing RNA during the induced differentiation of murine
      erythroleukemia (MEL) cells. This probe revealed two nuclear and one cytoplasmic
      RNA species. Nuclear small RNAs had a biphasic variation: a decrease followed by
      a reaccumulation. The cytoplasmic species was essentially non polysomal, and
      disappeared after the induced differentiation. The presented results suggest that
      the regulation of these RNAs is associated to cell proliferation and
      differentiation respectively.

PMID- 1998523
TI  - The nucleolar localisation signal of the HTLV-I protein p27rex is important for
      stabilisation of IL-2 receptor alpha subunit mRNA by p27rex.
AB  - In this study we investigated the mechanism of stabilisation of IL-2 receptor
      alpha subunit mRNA by the HTLV-I protein p27rex. We tested the role of the
      nucleolar targetting signal in rex by introducing mutations. Three deletion
      mutants could not express rex protein in the nucleolus and although protein was
      still expressed in the nucleoplasm none of the mutants could stabilise IL-2R
      alpha mRNA. A substitution mutant could be expressed in the nucleolus and could
      also stabilise IL-2R alpha mRNA. The data show that the nucleolar targetting
      signal is crucial for stabilisation of IL-2R alpha mRNA by rex and raise the
      possibility that transport of mRNA from nucleus to cytoplasm can involve the
      nucleolus.

PMID- 1998524
TI  - Effect of myricetin and other flavonoids on the liver plasma membrane Ca2+ pump.
      Kinetics and structure-function relationships.
AB  - Thirty-three different flavonoids were screened for their ability to influence
      ATP-dependent Ca2+ uptake by rat liver plasma membrane vesicles. Nine of the
      flavonoids, at a concentration of 100 microM inhibited Ca2+ uptake by more than
      20%. The remaining 24 flavonoids exhibited little or no effect. The relative
      order of potency of the more biologically active flavonoids was myricetin greater
      than butein greater than phloretin = luteolin greater than eriodictyol = silybin.
      Myricitrin and phloridzin, the glycosides of myricetin and phloretin,
      respectively, had no effect. The degree of inhibition caused by myricetin was
      concentration dependent and was also affected by the preincubation time. After 10
      min of preincubation, 52 microM myricetin lowered the initial rate of 45Ca uptake
      by 50%. The inhibition by myricetin was non-competitive with respect to Mg-ATP
      and of a mixed type with respect to Ca2+. At a concentration of 100 microM,
      myricetin had no effect on several plasma membrane enzymes such as 5'
      nucleotidase, alkaline phosphatase and a Ca2(+)-activated ATPase but inhibited
      K(+)-dependent p-nitrophenyl phosphatase by 83%. The ATP-dependent Ca2+ transport
      systems located on the plasma membrane or endoplasmic reticulum derived from
      other tissues were also inhibited by myricetin. Analysis of the structure
      activity relationship revealed that lipid solubility and polyhydroxylation
      particularly at positions 5,7,3' and 4' of the flavonoid ring structure enhanced
      the ability of the flavonoid to inhibit Ca2+ uptake. The results suggest that
      inhibition of Ca2+ transport activity probably involves the interaction of the
      phenolic groups of the flavonoid with the Ca2+ transporting protein.

PMID- 1998525
TI  - The inhibition of lipid peroxidation by cinnarizine. Possible implications to its
      therapeutic and side-effects.
AB  - Cinnarizine has antivasoconstrictor properties and improves red-cell
      deformability. Its major side-effects are the induction of extrapyramidal
      reactions. It is a calcium antagonist, but it was suggested that its effects may
      depend on other mechanisms, namely on antiperoxidant properties. We have studied
      these properties in different biological systems, intact red-cells included. The
      occurrence of lipid peroxidation was determined by the formation of 2
      thiobarbituric acid reactive products. Cinnarizine was found to inhibit
      spontaneous lipid peroxidation in rat liver homogenates, copper-induced lipid
      peroxidation in human plasma and copper-induced and hydrogen peroxide-induced
      lipid peroxidation in human red-cells. In red-cells, the inhibition of lipid
      peroxidation is accompanied by the inhibition of hemolysis. Copper-induced red
      cell lipid peroxidation is 85% inhibited by as little as 5 microM cinnarizine.
      The antioxidant activity of cinnarizine may contribute to explain some of the
      effects of this drug.

PMID- 1998526
TI  - Salicylate inhibits human placental sulphate transport in vitro.
AB  - The effect of salicylate on sulphate transport by the human placenta has been
      studied using isolated brush-border membrane vesicles and placental tissue
      slices. Sulphate uptake by isolated vesicles was inhibited in a dose dependent
      fashion (K1 approximately 3 mM) by salicylate. It appears that this drug blocks
      sulphate accumulation in a non-competitive manner. Sulphate efflux from preloaded
      vesicles was also found to be markedly reduced by salicylate in a non-competitive
      fashion. Consistent with the vesicle studies salicylate inhibited sulphate
      transport by placental tissue slices. The results suggest that salicylate
      ingestion could compromise feto-placental sulphate homeostasis. In addition we
      have found that the aspirin-like drug, flufenamic acid, inhibits sulphate
      transport by isolated microvillus membrane vesicles.

PMID- 1998527
TI  - Reduced insulin binding to liver plasma membranes in inherently obese diabetic
      CBA/Ca mice.
AB  - Insulin binding to isolated liver plasma membranes was measured in mice from
      C57BL and LACG strains, and in normal and obese diabetic mice from the Bristol
      CBA/Ca colony. A simple and rapid three-step method for the preparation and
      purification of liver plasma membranes, using Percoll density gradient
      centrifugation was used. Both high and low affinity binding was detected in
      membranes from all four groups of mice. The Kd values for binding were similar in
      all groups, but the insulin binding capacity (Bmax) at low and high affinity was
      significantly reduced in obese CBA mice compared to age-matched lean controls. It
      is proposed that insulin receptor down-regulation may account for the insulin
      resistance observed in spontaneously obese diabetic CBA mice.

PMID- 1998528
TI  - Inhibition of muscarinic cholinergic receptors by disulfide reducing agents and
      arsenicals. Differential effect on locust and rat.
AB  - Muscarinic receptors are altered by sulfhydryl reagents. Arsenic compounds, which
      have been used as insecticides, exert their toxic effects by combining with
      sulfhydryl groups. We compared the action of arsenicals and other sulfhydryl
      reagents on the muscarinic receptor from invertebrate and vertebrate species
      (locust and rat). Disulfide-reducing reagents dithiothreitol (DTT) and British
      Anti-Lewisite (BAL), but not arsenicals, inhibited [3H]quinuclidinyl benzilate
      ([3H]QNB) binding. However, after disulfide reduction, arsenicals caused a
      further inhibition of muscarinic binding. The effect of DTT + arsenicals was
      largely irreversible. The locust receptors were more sensitive to the action of
      both disulfide reagents either in the absence or presence of arsenicals than the
      rat receptors. The sulfhydryl reagent p-chloromercuric benzoate (PCMB) was more
      effective at inhibiting the locust receptors than the rat receptors, but addition
      of arsenicals did not cause further inhibition in either the locust or rat
      receptors. In locust, DTT + cacodylate and DTT + arsenite caused a reduction in
      the number of sites without modifying the affinity of [3H]QNB binding. In rat,
      DTT + arsenite caused a decrease in the affinity, while DTT + cacodylate caused a
      decrease in the affinity of [3H]QNB binding and its number of sites. Competition
      experiments after DTT + cacodylate showed that the IC50 and the Hill coefficient
      (nH) remained unchanged in the locust. In the rat, the IC50 for atropine was
      increased without alteration in the nH, and both parameters were increased for
      carbachol. These results are explained assuming that the binding site of the
      locust receptor has a disulfide group similar to that of the mammalian receptor,
      but that the hydrophobic interactions within the binding site are weaker in the
      locust receptor. The higher sensitivity of the insect receptor to sulfhydryl
      reagents could be of interest for developing methods of pest control.

PMID- 1998529
TI  - Lipid peroxidation in brain and lungs from mice exposed to hyperoxia.
AB  - Lipid peroxidation was measured in brains and lungs from mice which had been
      exposed to 100% O2 at 445 kPa, 515 kPa and 585 kPa for 30 min. These treatments
      produced varying degrees of convulsive activity and negligible to moderate lung
      damage. Lipid peroxidation was estimated by the thiobarbituric acid method and by
      analysis of Schiff bases. Lipid peroxidation did not increase in either lungs or
      brains after hyperbaric oxygen exposure, nor was there any difference between
      tissues from control or hyperoxic mice in the degree of lipid peroxidation which
      occurred during in vitro incubation of homogenates at 37 degrees in air for 150
      min. Similarly, no increased lipid peroxidation was seen in lung tissue from mice
      exposed to normobaric 100% O2 for either 60 or 72 hr.

PMID- 1998531
TI  - Stereochemical selectivity in the induction of cytochrome P450IVA1 (P452)
      dependent fatty acid hydroxylation and peroxisome proliferation.
AB  - Induction of hepatic microsomal cytochrome P450IVA1 and peroxisomal enzymes of
      the beta-oxidation spiral were observed when male Long Evans hooded rats were
      administered optically pure enantiomeric forms and a racemic mixture of a
      clofibrate analogue [2-[4-(4-chlorophenyl)benzyloxy]-2-phenylacetic acid] at a
      dose level of 80 mg/kg for 3 days. The R(-)-enantiomer was found to be a more
      potent inducer of microsomal cytochrome P450IVA1 and its associated lauric acid
      12-hydroxylase activity than its corresponding S(+)-antipode. This difference in
      potency was reflected by a eudismic ratio (R/S activity ratio) of approximately
      3, whereas the racemic mixture exhibited a potency intermediary between the two
      isomers. An identical enantiomeric selectivity was observed for the phenomenon of
      peroxisome proliferation as judged by induction of cyanide-insensitive palmitoyl
      CoA oxidation and the bifunctional protein of the peroxisomal beta-oxidation
      spiral. The highest potency was shown by the R(-)-isomer resulting in
      approximately a 3-6-fold increase over the control value. These increases was
      paralleled by an increase in total carnitine acetyl transferase activity with a
      eudismic ratio of approximately 4. In addition, immunochemical detection by
      Western blotting analysis for both the microsomal cytochrome P450IVA1 isozyme and
      the peroxisomal bifunctional protein was in agreement with the above modulation
      of catalytic activities. These results are therefore not inconsistent with the
      hypothesis that cytochrome P450IVA1 induction and peroxisome proliferation are
      intimately linked. Whether the observed stereochemical selectivity resides in
      xenobiotic recognition or disposition still remains to be determined.

PMID- 1998530
TI  - Codeine O-demethylation: rat strain differences and the effects of inhibitors.
AB  - The oxidative metabolism of more than 20 drugs (e.g. sparteine, debrisoquine,
      dextromethorphan) is mediated by cytochrome P450IID6. Codeine O-demethylation to
      morphine was recently demonstrated to co-segregate with the polymorphic
      metabolism of debrisoquine and dextromethorphan. The female Dark-Agouti rat (DA)
      is an animal model for the poor metabolizer phenotype (PM) using debrisoquine or
      dextromethorphan as substrates. Studies were carried out to evaluate codeine
      metabolism in liver microsomes from female DA and Sprague-Dawley (SD) rats. The
      intrinsic clearance of codeine to morphine was 10-fold lower in DA rats due to a
      5-fold higher Km (287 vs 49 microM) and a 2-fold lower Vmax (48 vs 94
      nmol/mg/hr). Nineteen drugs were tested for inhibition of codeine O
      demethylation. The four most potent competitive inhibitors were dextromethorphan
      (Ki = 2.53 microM), propafenone (Ki = 0.58 microM), racemic methadone (Ki = 0.3
      microM) and quinine (Ki = 0.07 microM). The differences in morphine formation
      from codeine between SD and DA rats and the inhibition results show that this
      animal model appears to be a suitable model for the human EM and PM phenotypes,
      respectively. These strains could be used to study the pharmacodynamic
      consequences of the genetic polymorphism in codeine O-demethylation, and the
      effects of metabolic inhibitors. The outcome of these studies could impact on the
      therapy of pain control.

PMID- 1998532
TI  - Sex differences in hepatic and renal cadmium accumulation and metallothionein
      induction. Role of estradiol.
AB  - The role of estradiol in sex differences in hepatic and renal cadmium
      accumulation and metallothionein (MT) induction was investigated. Male and female
      rats and castrated males pretreated with estradiol were injected either i.v. or
      s.c. with 10 mumol CdCl2/kg. Sex differences in cadmium accumulation and MT
      induction were apparent after s.c. but not i.v. administration. The female rats
      accumulated a significantly greater concentration of cadmium in their liver than
      did the males, as early as 1 hr after the s.c. injection. The elevated levels of
      cadmium in the females were maintained for at least 10 days. Pretreatment of
      castrated males with estradiol caused a similarly greater accumulation of cadmium
      in the liver. Hepatic MT levels peaked in the females at 24 hr and in males 48-72
      hr after the cadmium injection and then declined to lower levels. This
      superinduction of MT occurred only after the s.c. administration of cadmium. MT
      levels in both sexes plateaued 5 days after the s.c. injection to the levels that
      were similar to those seen in male and female rats 24 hr after an i.v. injection.
      In animals injected s.c. with cadmium the renal cadmium levels continued to rise
      for 5-10 days; however, in animals injected i.v. the levels stabilized within 2
      hr. The renal MT levels in the females were significantly higher than in the
      males. Estradiol pretreatment induced renal MT but did not affect renal cadmium
      accumulation. Thus, the sex differences in hepatic cadmium accumulation and MT
      induction are affected by the route and time after the administration of cadmium.
      Furthermore, estradiol causes a more rapid uptake of cadmium by the liver and
      also an enhanced induction of MT in both the liver and kidney.

PMID- 1998533
TI  - Studies on the mechanism of antitumor action of 2-desamino-2-methyl-5,8
      dideazaisofolic acid.
AB  - The new folate analogue, 2-desamino-2-methyl-5,8-dideazaisofolic acid, 2c, was
      synthesized and evaluated using a variety of biochemical and antitumor assays.
      For purposes of comparison, its 2-desamino, 2b, and 2-amino, 2a, counterparts, as
      well as N10-propargly-5,8-dideazafolic acid, 1a, and the corresponding 2
      desamino, 1b, and 2-desamino-2-methyl, 1c, modifications were included in these
      studies. Compound 2c was found to be a potent inhibitor of the growth of L1210
      and MCF-7 cells in culture, being only 2-fold and 5-fold less effective than 1c,
      respectively. However, although analogue 2c was 189-fold less inhibitory toward
      L1210 thymidylate synthase (TS) than 1c, its cytotoxicity was reversed completely
      by thymidine alone which suggests that the compound behaves as a TS inhibitor in
      cells. Enzymatically synthesized polyglutamates of 2c were substantially more
      inhibitory toward human TS than the parent compound. Compound 2c was the most
      efficient substrate for mammalian folyl-polyglutamate synthetase of the compounds
      studied having a Vmax/Km nearly 12-fold larger than 1c. Both 1c and 2c were
      effective inhibitors of the uptake of [3H]methotrexate into MOLT-4 cells,
      implying that each is efficiently transported into tumor cells. These results
      suggest that a weak inhibitor of TS in vitro can be a potent cytotoxic agent if
      it can readily gain entry into target cells and be converted to polyglutamated
      metabolites.

PMID- 1998535
TI  - Treatment with anabolic steroids increases the activity of the mitochondrial
      outer carnitine palmitoyltransferase in rat liver and fast-twitch muscle.
AB  - Treatment of male rats with the anabolic steroids fluoxymesterone or
      methylandrostanolone increased the activity of the outer carnitine
      palmitoyltransferase in liver and fast-twitch muscle mitochondria. This effect
      was not potentiated by physical exercise and was not observed in heart and slow
      twitch muscle mitochondria. Anabolic steroids did not affect the sensitivity of
      the liver enzyme to inhibition by malonyl-CoA. The data presented herein suggest
      that androgens may have an important physiological role in the regulation of
      fatty acid oxidation in liver and fast-twitch muscle mitochondria. In addition,
      our results are at odds with the notion that (most of) the metabolic effects of
      anabolic steroids on muscle are only evident when physical training is parallely
      performed.

PMID- 1998534
TI  - Transient enhancement of multidrug resistance by the bile acid deoxycholate in
      murine fibrosarcoma cells in vitro.
AB  - Recent studies have implicated protein kinase C (PKC) activation in drug
      resistance in vitro. PKC can be activated directly by phorbol-ester tumor
      promoters as well as by the bile acid deoxycholate. In this report, we
      demonstrate that deoxycholate, at concentrations that are chronically present in
      the lumen of the colon in vivo, mimicked phorbol-ester tumor promoters by
      protecting Adriamycin (ADR)-sensitive and multidrug-resistant (MDR) murine
      fibrosarcoma UV-2237M cells from ADR cytotoxicity. Deoxycholate also enhanced the
      resistance of the MDR cell line UV-2237M-ADRR to the cytotoxic effects of
      vincristine and vinblastine. In contrast to cytotoxic drug-selected MDR
      phenotypes, deoxycholate-induced drug resistance was transient and required
      continuous exposure to the bile acid. The protein kinase inhibitor H7 completely
      reversed the protection against ADR cytotoxicity conferred on UV-2237M-ADRR cells
      by deoxycholate, providing evidence that deoxycholate exerts its protective
      effects by a mechanism that involves stimulation of protein phosphorylation and
      not merely by detergent effects on membrane permeability. PKC consists of a
      family of at least seven isozymes with distinct modes of activation and substrate
      specificities. We previously reported that MDR UV-2237M cell lines contain higher
      levels of PKC activity than the parental ADR-sensitive UV-2237M cell line
      (O'Brian et al., FEBS Lett 246: 78-82, 1989). The present report shows that PKC
      III is a major PKC isozyme in ADR-sensitive and MDR UV-2237M cell lines. Thus,
      the resistance to ADR induced by the phorbol esters in UV-2237M cell lines
      provides strong evidence that PKC-III activation confers protection against ADR
      on ADR-sensitive and MDR UV-2237M cell lines. Furthermore, since deoxycholate is
      an endogenous molecule in the colonic epithelium, our finding that physiological
      concentrations of deoxycholate can render cells more resistant to
      chemotherapeutic drugs in vitro may have implications for the biology and therapy
      of intestinal cancers.

PMID- 1998538
TI  - MediPlan act of 1990.

PMID- 1998536
TI  - The alpha beta monomer of the insulin receptor has hormone-responsive tyrosine
      kinase activity.
AB  - Insulin receptors from turkey erythrocyte membranes exist as monomers and dimers
      when membranes are solubilized with detergent. We examined the ability of
      monomers and dimers to act as protein kinases to effect both autophosphorylation
      of the receptor and phosphorylation of an exogenous substrate. After separation
      by sucrose-density-gradient centrifugation, only receptor dimers show significant
      basal and insulin-stimulated kinase activity, whereas material at the position of
      receptor monomers is not active. Partial reduction of the membrane-bound
      receptors with dithiothreitol, however, produces a receptor monomer containing an
      alpha and a beta chain which has protein kinase activity similar to that of the
      original dimers. With rat adipocyte plasma membranes, which in the absence of
      reducing agents only contain receptor dimers, reduction with dithiothreitol also
      produces monomers with receptor kinase activity. Receptor monomer hormone
      dependent kinase activity is insensitive to receptor concentration and shows
      stimulation after immobilization on an affinity support.

PMID- 1998537
TI  - The solution conformations of a mutant trp operator determined by n.m.r.
      spectroscopy.
AB  - The principal conformational features of the mutant trp operator
      [d(CGTACTGATTAATCAGTACG)2] have been determined by n.m.r. at different
      temperatures. The sugar puckers were determined from J-resolved spectroscopy and
      high-resolution homonuclear Hartmann-Hahn spectroscopic (HOHAHA) experiments.
      Extensive one-dimensional nuclear-Overhauser-enhancement (NOE) data sets were
      acquired at 25 degrees C using irradiation times of 50, 100, 200, 300 and 500 ms
      to generate sufficient NOE information to determine the individual nucleotide
      conformations, and place limits on the local helical parameters, using multi-spin
      least-squares fitting and searching in conformation space with the program NUCFIT
      [Lane (1990) Biochim. Biophys. Acta 1049, 189-204]. The conformations of the
      nucleotides are well determined, and show significant sequence-dependent
      variation. Pyrimidine residues on average have a wider range of sugar
      conformations and smaller glycosidic torsion angles than purine residues. The
      helical parameters are in general less well determined, though clear evidence was
      obtained for sequence-dependent variation of the helical twist. The overall mean
      fractional deviation of the calculated from the observed NOEs was 0.108. The
      conformations of the base-pairs TAAT are temperature-dependent [Lane (1989)
      Biochem. J. 259, 715-724]. NOESY spectra were recorded at 10, 25 and 40 degrees
      C, using mixing times inversely proportional to the overall tumbling time to
      allow changes in the conformation to be described. A more detailed analysis was
      made using one-dimensional NOEs collected for nucleotides involved in the
      conformational transitions. There are significant temperature-dependent changes
      in the conformations of the central base-pairs from T9 to T13 with the largest
      changes in the glycosidic torsion angle occurring for A11 and A12 (up to 30
      degrees). The orientation of the base-pairs T9-A12:T10-A11 also changes, with an
      increase in the base-pair roll and an unwinding of the helix as the temperature
      is increased. The conformational changes are qualitatively similar to those
      observed in a related sequence (Lefevre, Lane & Jardetzky (1988) Biochemistry 27,
      1086-1094]. The conformation is also similar to the wild-type sequence and to
      that observed in the crystal state in the complex with the trp holorepressor. The
      similarity suggests that the mutation produces a poorer operator by virtue of
      removal of essential functional groups within the major groove.

PMID- 1998539
TI  - Writing for journal publication.

PMID- 1998540
TI  - Nursing QA and ET working together. A clinical evaluation of the Iris 10,000 Dry
      Flotation Pad.

PMID- 1998541
TI  - Nephrostomy dressing change procedure.

PMID- 1998542
TI  - Topical wound management. To betadine or not to betadine?

PMID- 1998543
TI  - Nursing to promote healing.

PMID- 1998544
TI  - Study project: the use of a topical circulatory stimulant for the treatment of
      pressure ulcers.

PMID- 1998545
TI  - An approach to treating skin tears.

PMID- 1998546
TI  - Urinary incontinence.
AB  - This CEU program will assist the nurse in planning quality care for the patient
      who experiences urinary incontinence. A review of the urinary system is presented
      so that an adequate understanding of the types and causes of urinary incontinence
      may be achieved. Assessment data to be obtained by the nurse are included and
      appropriate nursing interventions are discussed.

PMID- 1998547
TI  - Changing demands in AD nurse education.

PMID- 1998548
TI  - Disseminating intravascular coagulation (DIC): nursing interventions.
AB  - When nurses provide care for seriously debilitated patients, a secondary illness
      such as DIC is often inevitable. Knowledge of the disease and appropriate nursing
      and medical interventions are essential to deter rapid deterioration of the
      patient's condition.

PMID- 1998549
TI  - A holistic approach to infection prevention and control.

PMID- 1998550
TI  - Training of nurses in the USSR: historical review.

PMID- 1998551
TI  - What nurses don't know about AIDS.
AB  - As nurses care for ever increasing numbers of AIDS patients, they will face
      increased challenges that will tax knowledge and skill levels. To make the
      appropriate assessments and decisions about care and educational needs of the
      patient, the nurse needs a complete knowledge base that includes information
      about the pathophysiology, physiologic needs of the patient, and the diagnostic
      tools related to the disease process.

PMID- 1998552
TI  - AIDS--the legal issues.

PMID- 1998553
TI  - Nursing options.

PMID- 1998554
TI  - Understanding water intoxication. Part I in a II-Part series.
AB  - While knowledge exists concerning the symptoms and possible causes of water
      intoxication, the exact etiology remains unclear. If proper nursing strategies
      are to be developed, it is crucial to carefully assess each patient with
      polydipsia and plan interventions related to what is known about that patient.

PMID- 1998556
TI  - Impressing the boss who criticizes you.
AB  - The nurse's response to criticism is an important dimension of the supervisor
      nurse relationship. A nurse who responds to criticism in a way that the
      supervisor finds inappropriate can damage the relationship and impair chances of
      job success. On the other hand, a nurse who accepts criticism and uses it to
      modify personal behavior can positively impress the supervisor and can use
      criticism to aid professional advancement.

PMID- 1998555
TI  - Teaching osteoporosis prevention.
AB  - The role of nutrition is critical in the prevention of osteoporosis. Teenagers
      and women, who consume adequate calcium throughout life and consider nutritional
      factors that may impair their bodies' use of calcium, can do much to prevent the
      onset of osteoporosis. The nurse's role in this prevention is described.

PMID- 1998557
TI  - Nurse externship ... What is it? ... Why is it?

PMID- 1998558
TI  - Steroid abuse.

PMID- 1998560
TI  - Moments.

PMID- 1998559
TI  - Diabetes mellitus. Types I and II.
AB  - IDDM and NIDDM are classifications of Diabetes Mellitus (DM) but should be
      recognized as having related but different treatment regimens; different
      problems, but the same desired outcome. That outcome is maintenance of normal
      blood glucose levels and prevention of acute and chronic complications. Nurses
      who care for patients with diabetes and who provide diabetes education need to
      continually assess patients' understanding about DM and its treatment. As a
      result, patient independence is fostered, the likelihood of adherence is
      increased, and optimal outcomes of the management of diabetes are promoted.

PMID- 1998561
TI  - Legal issues in the care of patients with urinary incontinence.

PMID- 1998562
TI  - Fellowship proliferation. Part II: Impact and long-range trends.

PMID- 1998563
TI  - Indomethacin inhibition of middle ear bone resorption.
AB  - Localized osteoclastic bone resorption is responsible for the pathological
      changes within the middle and inner ear, which result in hearing loss and vertigo
      in chronic otitis media and otosclerosis. The local control of osteoclastic bone
      resorption is incompletely understood. Various small, locally active molecules,
      cytokines, have been shown to affect resorptive processes. Additionally,
      prostaglandins and their inhibitors have been shown to modulate the resorptive
      process in a number of in vitro studies. In this study, indomethacin, a
      cyclooxygenase inhibitor, was tested in a model of localized bone resorption, the
      pressurized gerbil bulla. After the experimental period, indomethacin was found
      to inhibit the number of osteoclasts and the resorptive area on the inner surface
      of the bulla. Therefore, it is likely that endogenous cyclooxygenase metabolites
      are intermediates in the sequence of cellular events, which results in localized
      bone resorption as in some systemic models.

PMID- 1998564
TI  - Collagen injections. A case study in the erosion of the medical profession.
AB  - Physicians as professionals are people dedicated to promoting the health and
      welfare of their patients rather than simply catering to patient requests and
      desires. Collagen injections are examined to determine whether or not they can be
      considered legitimate medical treatment to be offered by physicians. It is
      concluded that until a more vigorous clinical effort is made to determine the
      efficacy of the injections in promoting the health and welfare of recipients, it
      is not clear that they constitute medical treatment. It is argued that the safety
      of the injections coupled with a patient's desire for them is insufficient to
      constitute the injections being considered medical treatment.

PMID- 1998565
TI  - Endoscopic repair of supraglottic laryngeal clefts.
AB  - We describe the technique of endoscopic diagnosis and endoscopic surgical repair
      used in the management of supraglottic interarytenoid laryngeal clefts in 11
      children seen between 1981 and 1988 at the Hospital for Sick Children, London,
      England. Six of the children had primary type I clefts that required endoscopic
      repair. The symptoms included inspiratory stridor, choking during eating, and
      aspiration. Five of the children had previous transcervical repair of type II
      clefts that had partial breakdown in the interarytenoid area causing symptoms of
      aspiration, which required secondary repair endoscopically. All the patients had
      successful microlaryngoscopic closure; in two children, however, the breakdown of
      the repair necessitated repeated endoscopic correction. The only complication
      occurred in a case of postoperative supraglottitis, which was successfully
      managed with intubation and antibiotics. We conclude that endoscopic repair is a
      useful and reliable technique and an elegant alternative to the open
      transcervical approach for the closure of supraglottic laryngeal clefts.

PMID- 1998566
TI  - Endoscopic and computed tomographic findings in ostiomeatal sinus disease.
AB  - Previously, there has been no organized format for the documentation of the
      findings of the nasal endoscopy and the coronal computed tomographic sinus scan.
      The findings from 100 nasal endoscopies and computed tomographic scans were
      reviewed and summarized. The summarized findings were incorporated into two forms
      -"the Nasal Endoscopy Exam Form" and the "Computed Tomographic Scan Findings
      [form]"--utilizing computerized graphics techniques. The forms are presented
      along with their illustration of pathologic ostiomeatal findings. These forms
      represent a method of documentation of nasal endoscopic and coronal computed
      tomographic scan findings. They may be used in the demonstration of disease,
      treatment, planning, resident training, communication of information, and
      assisting in a future classification of degrees of severity of sinus disease.

PMID- 1998568
TI  - Circulating C1q-binding macromolecules and their relationship to radiographic
      characteristics of laryngeal cancer.
AB  - Circulating macromolecules capable of binding the first component of complement
      (C1qBM) may represent subcellular components of tissue/tumor debris generated
      from rapidly proliferating invasive disease. Thirty-eight patients were randomly
      selected from 74 untreated patients with laryngeal cancer on the basis of disease
      stage and C1qBM levels. C1qBM levels were correlated with computed tomographic
      evidence of tumor necrosis and/or thyroid cartilage destruction. Results show
      that patients with stage III/IV disease with tissue necrosis and/or cartilage
      invasion had demonstrably higher C1qBM levels than did individuals with similarly
      staged disease with no evidence of these radiographically defined characteristics
      (120 +/- 81 micrograms/mL vs 18 +/- 15 micrograms/mL); the strongest association
      was reflected by the area of necrosis within regional lymph metastases. Elevated
      C1qBM level in patients with stage III/IV laryngeal cancer thus reflects highly
      aggressive disease, which is less responsive to therapeutic intervention.

PMID- 1998567
TI  - 5-year results of cisplatin and fluorouracil infusion in head and neck cancer.
AB  - As part of the developmental process for the Head and Neck Intergroup trial of
      adjuvant chemotherapy for advanced resectable head and neck carcinoma, in 1981
      the Radiation Therapy Oncology Group, Philadelphia, Pa, conducted two
      nonrandomized pilot studies using chemotherapy consisting of three courses of
      cisplatin and fluorouracil infusion. Chemotherapy was administered prior to
      surgery in 42 patients (induction) and after surgery in an additional 29 patients
      (sequential). The populations were roughly comparable with respect to tumor site
      and stage. Twelve of the 42 patients in the induction group and seven of the 29
      in the sequential group are alive and with no evidence of disease at the last
      reported follow-up. The median survival was 31 months in the sequential group vs
      20 months in the induction group. Only two of the 26 patients with less than a
      complete clinical response following induction chemotherapy are still alive.
      Twenty-seven of the 42 patients who received induction chemotherapy did not
      undergo surgery as initially planned. Despite the lack of surgery, at 5 years the
      survival between the two groups was not significantly different (27% for the
      induction group vs 23% for the sequential group).

PMID- 1998569
TI  - Radiotherapy. The mainstay in the treatment of early glottic carcinoma.
AB  - Early squamous cell carcinoma of the glottis may be effectively treated with
      surgery or radiation therapy. Controversy exists as to whether radiation therapy
      effects survival at the expense of vocal function by ultimately requiring more
      total laryngectomies for salvage of local tumor recurrence. This study reviewed
      the medical records of 185 patients with T1 or T2, NO invasive squamous cell
      carcinoma of the glottis treated with primary radiation therapy between 1969 and
      1984. All patients were followed up for a minimum of 5 years after completion of
      therapy. One hundred sixty-one patients met the criteria for local control
      analysis. Radiation therapy controlled disease in 93% (105 of 113) of patients
      with T1 lesions and 73% (38 of 48) of those with T2 tumors. Ultimate control of
      disease for T1 and T2 lesions, including surgical salvage, was 111 (98%) of 113
      and 44 (92%) of 48 patients, respectively. The rate of successful surgical
      salvage was 75% (T1) and 70% (T2). The T2 lesions with impaired vocal cord
      mobility or anterior commissure disease were identified as being at increased
      risk for recurrence after primary radiation therapy. Overall voice preservation
      was 90%. Our data demonstrate that radiation therapy effects disease-free
      survival rates that are comparable to those produced by surgery, without
      sacrificing voice. Although a small percentage of patients with selected early
      glottic lesions may be more effectively treated with primary conservation
      surgery, these data do not support a change in philosophy concerning primary
      treatment of early glottic cancer with radiation therapy.

PMID- 1998571
TI  - Primary parotid malignancies. A clinical and pathologic review.
AB  - One hundred ninety-four patients with primary malignant tumors of the parotid
      gland who underwent surgery at the Mayo Clinic (1970 through 1987) are reviewed.
      Survival patterns were analyzed using the Kaplan-Meier product-limit method that
      separated histologic results into three significantly different groups. Survival
      rate was highest for patients with acinic cell, adenoid cystic, and low-grade
      mucoepidermoid carcinomas; intermediate for patients with high-grade
      mucoepidermoid carcinomas; and lowest for the remaining six histologic types
      encountered. Cox multiple linear regression was used to identify patient and
      tumor characteristics with greatest prognostic significance. In order of
      decreasing strength, regional metastatic involvement, pain, male gender, grade,
      stage, and advancing age all demonstrated independent prognostic significance.
      Fifty-three percent of patients requiring facial nerve sacrifice were
      asymptomatic at presentation. A high positive correlation was observed between
      advancing grade and stage.

PMID- 1998570
TI  - Primary sarcomas of the major salivary glands.
AB  - Sarcomas arising in the major salivary glands are rare. This article presents the
      clinicopathologic features of 11 patients with primary sarcomas of the parotid
      gland (eight men and three women aged 7 to 75 years; mean age, 42 years). The 11
      sarcomas were histologically typified as follows: three malignant fibrous
      histiocytomas and two each of neurosarcomas, rhabdomyosarcomas, fibrosarcomas,
      and osteosarcomas. Four patients experienced disease recurrences, and seven
      patients developed metastases. Seven patients died of their sarcomas, with a mean
      survival time of 30 months. Four patients were alive from 5 to 12 years (one each
      with angiomatoid malignant fibrous histiocytoma, embryonal rhabdomyosarcoma,
      fibrosarcoma, and neurosarcoma). Prognosis correlated with size of the neoplasm,
      type of sarcoma, and histologic grade. In this respect, salivary gland sarcomas
      behaved in identical fashion to their soft-tissue counterparts.

PMID- 1998572
TI  - Reconstruction of pediatric larynx and upper trachea with the sternohyoid rotary
      door flap.
AB  - The sternohyoid myocutaneous flap, the rotary door flap, is optimally oriented to
      serve in laryngotracheal reconstruction. It provides immediate, highly
      vascularized lining and structural support to the augmented airway. Therefore, it
      is one of the most versatile alternative methods available for surgical
      reconstruction of the stenosed larynx and trachea. Thirteen of 14 patients who
      were managed by the rotary door flap technique have been successfully
      decannulated. The features of the flap and the surgical technique are described
      with reference to modifications in the pediatric age group.

PMID- 1998573
TI  - Nasal reconstruction with articulated irradiated rib cartilage.
AB  - Nasal structural reconstruction is a formidable task in cases where there is loss
      of support to both the nasal dorsum and tip. A multitude of surgical approaches
      and materials have been used for the correction of the saddle-nose deformity with
      varying degrees of success. Articulated irradiated rib cartilage inserted through
      an external rhinoplasty approach was used to reconstruct nasal deformities in 18
      patients over a 6-year period. Simultaneous use of a midline forehead flap to
      reconstruct the overlying soft tissue was required in four cases. Follow-up
      ranged from 1 to 6 years (mean, 2.8 years). Results were rewarding in most cases
      with marked improvement in nasal support and airway. Revision and/or replacement
      secondary to trauma or warping of the graft was required in four cases. None of
      the patients exhibited infection, extrusion, or noticeable resorption. A
      description of the surgical technique, review of all the cases, and
      recommendation for continued use of this graft material are discussed.

PMID- 1998574
TI  - Noncongenital hereditary hearing loss in children. Prospective documentation.
AB  - Younger siblings of children with sensorineural hearing loss of possible
      hereditary cause underwent interval audiologic examination. Seven siblings (in
      unrelated families) were found to have progressive sensorineural hearing loss
      despite early audiograms documenting normal hearing levels for age. Continued
      testing of these children allowed for early identification and intervention. We
      advocate regular otolaryngologic and audiologic follow-up even after normal
      audiologic assessments are made for younger siblings of children with documented
      sensorineural hearing loss, unless a definite nongenetic origin of the hearing
      loss in the older child is known. Recessive sensorineural hearing loss with onset
      in infancy or childhood may present with no antecedent family history and with
      normal behavioral audiograms early in life.

PMID- 1998575
TI  - Pathologic quiz case 2. Pilomatricoma (calcifying epithelioma of Malherbe).

PMID- 1998576
TI  - Pathologic quiz case 1. Nodular fasciitis of the parotid gland.

PMID- 1998577
TI  - Indapamide to treat Meniere's disease.

PMID- 1998578
TI  - Manometry and electromyography of the pharyngeal muscles in patients with
      dysphagia [correction of dysphasia].

PMID- 1998579
TI  - Transseptal fracture displacement approach for treatment of pituitary lesion.

PMID- 1998580
TI  - Facial palsy following local anesthetic infiltration for middle ear surgery.

PMID- 1998582
TI  - Prevention of human rabies in 1989.

PMID- 1998581
TI  - Pseudocyst of the auricle.

PMID- 1998583
TI  - Expanded programme on immunization. Global Advisory Group--Part II.

PMID- 1998584
TI  - Severe aplastic anaemia: the patient without a HLA-identical sibling.

PMID- 1998585
TI  - Identification of haemophilia B patients with mutations in the two calcium
      binding domains of factor IX: importance of a beta-OH Asp 64----Asn change.
AB  - The polymerase chain reaction procedure (PCR) coupled with direct sequencing has
      been used to screen a panel of haemophilia B patients. This analysis has
      identified, amongst others, several mutations in the functionally important gla
      and type B EGF domains of factor IX, both of which are known to bind calcium.
      Type B EGF domains are widely distributed in proteins; located within these
      domains are highly conserved amino acid residues important for the formation of a
      high-affinity calcium binding site. One prominent feature of these domains is a
      highly conserved beta-hydroxylated Asp or Asn residue. Of particular interest is
      the identification of one patient, with a substitution of the beta-hydroxy Asp-64
      residue normally present in factor IX for Asn. This change results in a
      functionally defective factor IX molecule with altered calcium binding
      properties. To explain the functional abnormality caused by this substitution of
      one amino acid residue for another which is commonly found at the equivalent
      position in other proteins with type B EGF domains, we propose the existence of
      additional conserved residues within this domain, which are important for calcium
      binding, and which correlate with whether the beta-hydroxylated residue is Asp or
      Asn.

PMID- 1998586
TI  - K+ efflux in deoxygenated sickle cells in the presence or absence of DIOA, a
      specific inhibitor of the [K+, Cl-] cotransport system.
AB  - The ouabain bumetanide resistant (OBR) K+ efflux was investigated in deoxygenated
      sickle cells in comparison to oxygenated ones, by using a specific inhibitor of
      the [K+, Cl-] co-transport system, [(DihydroIndenyl)Oxy] Alkanoic acid (DIOA). A
      DIOA sensitive and a DIOA resistant K+ efflux were measured in deoxygenated
      sickle cells. The DIOA sensitive K+ efflux shared the properties of the [K+, Cl-]
      co-transport system, being stimulated by decreased pH and hypoosmolarity. This
      DIOA sensitive K+ efflux represented 70% of the total K+ efflux at pH 7.0 and at
      low pO2 (10-15 mmHg). Thus, a small reduction in Ph effectively stimulated the
      [K+, Cl-] co-transport system in deoxygenated condition, and this may contribute
      significantly to the sickle cell dehydration. We conclude that at pH lower than
      7.4, the [K+, Cl-] co-transport system is permanently activated in sickle cells
      and leads to sickle cell dehydration in both oxygenated and deoxygenated
      conditions.

PMID- 1998587
TI  - Autoimmune neutropenia due to NA1 specific antibodies in primary biliary
      cirrhosis.

PMID- 1998588
TI  - Acute tumour lysis syndrome in a patient with acute lymphoblastic leukemia after
      a single dose of prednisone.

PMID- 1998590
TI  - Cutaneous vasculitis with myelodysplastic syndromes.

PMID- 1998589
TI  - Recurrent venous thrombosis associated with inherited deficiency of heparin
      cofactor II.

PMID- 1998591
TI  - Practical considerations in the analysis of chromosomal deletion breakpoints by
      pulsed field gel electrophoresis.

PMID- 1998592
TI  - Evidence that exposure to fibrinogen or to antibodies directed against Mac-1
      (CD11b/CD18; CR3) modulates human monocyte effector functions.
AB  - We have recently shown that the treatment of fibrinogen-coated monocytes (MO)
      with anti-fibrinogen as well as the exposure of MO to surface-bound fibrinogen
      (Fg) or to albumin haptenized with the Fg C-gamma-terminal pentadecapeptide,
      induces on oxidative burst. Using chemiluminescence (CL) for indicating an
      oxidative burst, and the ingestion of IgG-coated erythrocytes as a test of
      phagocytosis, we have now studied the impact of Fg on MO effector functions. MO
      that had been either pretreated with Fg and washed, or that were exposed to
      surface-adsorbed Fg, exhibited impaired Fc receptor-mediated phagocytosis. A
      similar impairment was observed when MO were pretreated with activating agents
      such as phorbol myristate acetate, n-formyl-methionyl-leucyl-phenylalanine (fMLP)
      or the calcium ionophore A23187. Moreover, following exposure to Fg or IgG, MO
      exhibited a reduced oxidative burst upon stimulation with a variety of agents.
      Similarly, MO pretreated or coincubated with anti-Mac-1 exhibited a reduced
      oxidative burst upon stimulation. Our results raise the possibility that
      inflammatory mononuclear phagocytes experience a functional modulation upon
      encountering fibrin by interacting with specific receptors for fibrin(ogen). This
      type of modulation is analogous to effects induced by the triggering of Fc gamma
      receptors. MO showed a decreased oxidative burst when either pretreated or
      coincubated with anti-Mac-1 antibodies, whereas antibodies directed against other
      MO surface constituents had no, or a weak effect only. This is compatible with
      the suggestion that Mac-1 acts as a fibrin (ogen) receptor.

PMID- 1998593
TI  - In vivo effects of macrophage colony-stimulating factor on human monocyte
      function.
AB  - Macrophage colony-stimulating factor (M-CSF) is reported to enhance a variety of
      functions of mature monocyte/macrophages in vitro. We have examined the effects
      of a 2 h intravenous infusion of M-CSF obtained from human urine (hM-CSF) on
      haematological parameters and selected monocyte functions. There was a rapid,
      small, but consistent reduction in Hb concentration (mean 6.5 +/- 2.3%, P less
      than 0.0005 by paired t test) by the completion of the hM-CSF infusion and small,
      transient falls in platelet, monocyte and neutrophil counts were noted in the 2 h
      following the end of the infusion. No effect on monocyte or neutrophil CD11b
      cellular adhesion molecule expression was detected. Exposure to hM-CSF in vivo
      did not directly stimulate the monocyte respiratory burst, but increased the
      percentage of monocytes responding to f-met-leu-phe from 9.8 +/- 2.5 to 16.6 +/-
      4.2 (P less than 0.01). The number of candida ingested and degraded per 100
      monocytes increased from 101 +/- 14 pre-infusion to 160 +/- 22 post-infusion (P
      less than 0.01). There was a rapid increase in the numbers of monocytes entering
      a skin window membrane from a mean of 226 +/- 71 pre-infusion to 1064 +/- 404 at
      the end of the infusion, with no effect on neutrophil migration. These data show
      that the administration of hM-CSF enhances several of the functions of peripheral
      blood monocytes in vivo, and this may be of benefit in the treatment of selected
      infections.

PMID- 1998594
TI  - Interleukin 6, a possible autocrine growth and differentiation factor for the
      human megakaryocytic cell line, CMK.
AB  - CMK is a human cell line derived from a megakaryoblastic leukaemia. It has
      characteristics of the megakaryocytic lineage, such as the presence of platelet
      peroxidase, membrane glycoproteins (GP)Ib and GPIIb/IIIa, alpha-granules, and
      demarcation membranes. The cell line proliferates autonomously in serum
      containing medium. Here we report that the cell line expresses the gene for IL-6
      and releases small quantities of the cytokine into the medium. Addition of
      exogenous IL-6 to cultures seeded into medium was found to promote growth of the
      cells. Conversely, addition of a neutralizing anti-IL-6 antibody inhibited cell
      growth. These data support the notion that autocrine IL-6 is one of the factors
      accounting for autonomous growth of the cell line.

PMID- 1998595
TI  - Combined flow cytometric assessment of cell surface antigens and nuclear TdT for
      the detection of minimal residual disease in acute leukaemia.
AB  - To define more precisely the immunophenotype of lymphoid blast cells, a new flow
      cytometric technique for the simultaneous detection of surface antigens and
      nuclear terminal deoxynucleotidyl transferase (TdT) was established. After
      staining for the cell surface marker, mononuclear cells were treated with
      paraformaldehyde (1%) and methanol to permeabilize the cell membrane. Then the
      cells were stained by indirect immunofluorescence using a rabbit anti-human TdT
      antibody. Dilution experiments were performed to reveal the sensitivity of the
      described flow cytometric assay: 0.02% leukaemic cells could reliably be detected
      above background level among normal peripheral blood lymphocytes. It is concluded
      that the double-staining procedure described here is a sensitive tool that
      contributes to the detection of minimal residual disease in a substantial
      proportion of acute leukaemias.

PMID- 1998596
TI  - Acute myeloid leukaemia relapsing following interleukin-2 treatment expresses the
      alpha chain of the interleukin-2 receptor.
AB  - Immunotherapy with recombinant human Interleukin-2 (rhIL-2) was given to nine
      patients in first complete remission from acute myeloid leukaemia (AML). Five
      patients relapsed. The median time to relapse after commencing rhIL-2 was 26
      weeks (range 2-44). Four patients were studied at relapse. The morphological and
      cytochemical features at relapse and presentation were similar. Cytogenetic
      analysis at relapse in patients 1 and 3 showed a normal karyotype. At relapse,
      patient 4 had the abnormality 46,XY, t(2;3). Patient 2 had the chromosomal
      abnormality t(8;21) at presentation and relapse. Patients 3 and 4 with M5 AML
      relapsed rapidly at 2 and 9 weeks after starting rhIL-2 treatment. Relapse
      leukaemia cells had features normally associated with lymphoid development.
      Patient 3 was TdT positive, with rearranged immunoglobulin genes, and a
      proportion of cells expressing the CD7 antigen; patient 4 also expressed the CD7
      antigen. Relapse leukaemic cells from three of four patients expressed the alpha
      chain of the IL-2 receptor as assessed by flow cytometry. After overnight
      incubation and removal of T-lymphocytes the proportion of cells from these
      patients expressing the alpha chain increased from 15% to 61% (P less than 0.01).
      Using tritiated thymidine uptake to assess cell proliferation, two of three
      patients who expressed the IL-2 receptor alpha chain proliferated in response to
      1000 u/ml of rhIL-2 in vitro, with a stimulation index greater than 1.95 (P less
      than 0.05). Following rhIL-2 immunotherapy for AML, relapse cells may express an
      inducible form of the alpha chain of the IL-2 receptor, which can mediate a
      proliferative response. It is possible that rhIL-2 when administered to AML
      patients in remission, may induce relapse. This may be a particular risk in
      patients with the M5 subtype.

PMID- 1998597
TI  - Effect of pharmacologic manipulation of protein kinase C by phorbol dibutyrate
      and bryostatin 1 on the clonogenic response of human granulocyte-macrophage
      progenitors to recombinant GM-CSF.
AB  - The effect of pharmacologic manipulation of protein kinase C (PK-C) activity on
      the response of committed human myeloid progenitor cells (CFU-GM) to recombinant
      human granulocyte-macrophage colony stimulating factor (rGM-CSF) was assessed.
      Coadministration of the PK-C activating agents, phorbol dibutyrate (PDBu) or
      bryostatin 1, with rGM-CSF resulted in a dose-dependent and, under some
      conditions, highly synergistic increase in the number of CFU-GM. With optimal
      combinations, colony formation far exceeded that which could be obtained with
      high concentrations of rGM-CSF alone. High concentrations of PDBu (e.g. greater
      than or equal to 50 nM), but not bryostatin 1, completely inhibited the CFU-GM
      response. These inhibitory effects could be reversed by bryostatin 1, but not by
      high concentrations of rGM-CSF. Bryostatin 1 also potentiated colony formation in
      response to rGM-CSF, and blocked the inhibitory effects of high concentrations of
      PDBu in bone marrow cells highly enriched for progenitors bearing the MY-10
      antigen. The increase in CFU-GM induced by PDBu or bryostatin 1 was associated
      with little change in the morphologic type of colony observed. Continuous
      exposure of cells to the calcium ionophore, ionomycin (500 nM), reduced the
      number of granulocyte-macrophage colonies, but produced little change in the
      concentration-response of rGM-CSF and PK-C activating agents. Finally, the PK-C
      inhibitors H-7 and tamoxifen, when administered at concentrations exhibiting
      minimal inhibitory effects in the presence of rGM-CSF alone, led to no change or
      small increases in the numbers of colonies formed in response to rGM-CSF and
      bryostatin-1, and a substantial increase in the number of colonies formed in the
      presence of rGM-CSF and PDBu. These results suggest that PK-C activation may play
      a complex role in regulating the response of normal myeloid progenitors to growth
      factors such as rGM-CSF. They also raise the possibility that under some
      circumstances the phorbol ester PDBu may trigger events that inhibit the growth
      of myeloid progenitors, and that this process may be blocked by bryostatin 1.

PMID- 1998598
TI  - Origin and function of adherent lymphokine activated killer cells in patients
      with chronic myeloid leukaemia who relapse following bone marrow transplantation.
AB  - Adherent lymphokine activated killer (ALAK) cells are a subpopulation of
      activated natural killer (NK) cells with MHC unrestricted antitumour activity
      distinguished by their propensity to adhere to plastic in the presence of
      interleukin-2 (IL-2). We generated ALAK cells from seven patients with chronic
      myeloid leukaemia (CML) following Campath-1-depleted bone marrow transplantation
      (BMT). Five had relapsed and were in chronic phase, one had cytogenetic evidence
      of relapse and one had prior evidence of cytogenetic relapse but was in complete
      remission at time of study. Phenotypically the ALAK cells included both CD56+/CD3
      NK cells and CD56-/CD3+ T cells. The CD3- subpopulation were studied
      cytogenetically and their functional activity tested in a 4 h 51Cr release
      cytotoxicity assay using the pretransplant leukaemia cells as targets.
      Cytogenetic studies showed that the ALAK cells from six patients were Ph
      negative, and where donor and recipient were sex mismatched, ALAK cells were
      exclusively of donor origin. In one patient ALAK cells were Ph positive and of
      recipient origin in eight of nine metaphases. In the 51Cr release assay the ALAK
      cells showed significant lysis of the pretransplant leukaemia in five of the
      seven patients tested. These data indicate that in CML patients who relapse post
      BMT the NK cells are usually of donor origin but may be recipient-derived. In
      most patients these ALAK cells have antileukaemic activity in vitro.

PMID- 1998599
TI  - Refractory myelomatosis treated with mitoxantrone in combination with vincristine
      and prednisone (NOP-regimen): a phase II study. The Nordic Myeloma Study Group
      (NMSG)
AB  - In a phase II study, patients with refractory myelomatosis were treated with a
      combination chemotherapy (NOP regimen): mitoxantrone (bolus injection of 4 mg/m2
      on days 1-4), vincristine (continuous infusion of 0.4 mg/24 h on days 1-4) and
      prednisone (250 mg/d on days 1-4 and 17-20). The treatment was repeated every 4
      weeks. Ninety-two patients were treated after they were found refractory to
      treatment with melphalan and prednisone (and occasionally vincristine) (n = 50)
      or more intensive treatment regimens (n = 42) including anthracyclines (n = 18).
      Response (greater than or equal to 50% reduction of M protein) was obtained in 23
      patients and minor response (clinical improvement but less than 50% reduction in
      M protein) in 22 patients. The median duration of the response was 7.5 months.
      Equal response rates were observed irrespective of the type of previous
      treatment. The major toxicity was myelosuppression with severe granulocytopenia
      and infections. However, the frequency decreased throughout the cycles. The NOP
      treatment is recommended in refractory myelomatosis, especially in patients
      refractory to other intensive regimens. Patients in a poor clinical condition or
      with thrombocytopenia before treatment should have a reduced mitoxantrone dose in
      the first treatment cycles.

PMID- 1998600
TI  - Increased intraplatelet levels of platelet-derived growth factor and transforming
      growth factor-beta in patients with myelofibrosis with myeloid metaplasia.
AB  - Platelet-derived growth factor (PDGF) is thought to play some role in the genesis
      of fibrosis associated with myeloproliferative disorders. In addition,
      transforming growth factor-beta (TGF-beta) has been confirmed to promote fibrotic
      process. Both PDGF and TGF-beta have been shown to cooperate with epidermal
      growth factor (EGF) in regulating the growth of human marrow fibroblasts. All
      three are contained in platelet alpha-granules. We report the results of a study
      in patients with myelofibrosis with myeloid metaplasia (MMM). We evaluated PDGF,
      TGF-beta and EGF-like activities in circulating platelets from patients compared
      to healthy subjects. In contrast to EGF-like intraplatelet levels which were
      similar in patients and in normal donors (1-4 ng/10(9) platelets), we found
      constantly higher values for both PDGF and TGF-beta in MMM patients. In both
      radioimmunoassay (RIA) and assay for mitogenic activity on human bone marrow
      fibroblasts, PDGF levels were increased on the average 2-3.5-fold over the levels
      found in normal donors (P less than 0.01 and P less than 0.001, respectively).
      PDGF serum levels in patients were consistent with those found in platelets. In
      platelet-poor plasma (PPP), PDGF concentrations were undetectable or congruent to
      2 ng/ml in patients and in control donors as well. The total TGF-beta activity in
      platelet lysates, determined using a competitive radioreceptor binding assay on
      Swiss 3T3 mouse cells and an inhibition growth assay on CCL64 cells, was found 2
      3-fold increased in patients with MMM as compared to control subjects (P less
      than 0.003). These results emphasize that, not only PDGF, but also TGF-beta are
      implicated in the myelofibrosis with myeloid metaplasia.

PMID- 1998601
TI  - Antithrombin Vicenza, Ala 384 to Pro (GCA to CCA) mutation, transforming the
      inhibitor into a substrate.
AB  - Antithrombin (AT) Vicenza has been previously identified as a functionally
      abnormal antithrombin associated with familial thrombosis (Finazzi et al, 1985).
      It binds normally to heparin, but loses its affinity following interaction with
      thrombin: it is a poor inhibitor of thrombin. AT Vicenza was isolated from plasma
      by heparin-Sepharose and thrombin-Sepharose chromatography, fragmented with
      cyanogen bromide (CNBr) and its tryptic peptides were analysed by fast atom
      bombardment mass spectrometry mapping. An abnormal peptide mass 1112 was
      identified. Edman degradation confirmed a substitution of Ala to Pro in the
      sequence Ala 383-Arg 393. Polymerase chain reaction amplification of exon 6 of
      the gene followed by genomic sequencing, localized the mutation to codon 384, GCA
      to CCA. The same mutation has recently been reported in AT Charleville (Mohlo
      Sabatier et al, 1989). Sodium dodecyl-sulphate polyacrylamide gel electrophoresis
      of AT Vicenza (/Charleville) under non-reducing conditions revealed an apparent
      increase in mol. wt following interaction with thrombin: under reducing
      conditions the mol. wt was less than that of normal AT. This indicated cleavage
      and unfolding of the molecule. The site of cleavage was determined by incubation
      of AT Vicenza (/Charleville) with thrombin-Sepharose, reduction and S
      carboxymethylation and reverse phase FPLC. A peptide was identified with the NH2
      terminal sequence beginning Ser-Leu-Asn, demonstrating the cleavage had occurred
      at the reactive site of the variant. It is concluded that the Ala 384 to Pro
      substitution transforms AT Vicenza (/Charleville) from an inhibitor into a
      substrate.

PMID- 1998602
TI  - Quantification of platelet-bound immunoglobulins of different class and subclass
      using radiolabelled monoclonal antibodies: assay conditions and clinical
      application.
AB  - Quantification of platelet-bound immunoglobulins (PBIg) with radiolabelled murine
      monoclonal antibodies (mAbs) has been described only for IgG so far. Here we
      describe some modifications of this mAb radioimmunoassay (MARIA) and show that by
      using a panel of radiolabelled specific mAbs it is possible to quantify not only
      PBIgG but also PBIgG subclasses and PBIgM. Analysis by gel filtration showed that
      all anti-IgG and anti-IgG-subclass mAbs bound to their respective antigens in a
      ratio of about 1:1. However, the binding ratio for the anti-IgM Mab could not be
      established. There was a good correlation between the antibody-density per
      platelet as determined with the anti-IgG mAb and determined as the sum of the IgG
      molecules of different subclass per platelet (r = 0.90). Platelet fragments did
      not interfere in the assay. 89 normal healthy controls had 140 IgG molecules per
      platelet and bound 269 anti-IgM molecules per platelet (geometric means). In a
      study on the detection of PBIg in 147 thrombocytopenic patients, it appeared that
      the MARIA had a sensitivity of 61% and a specificity of 45% for the diagnosis of
      idiopathic thrombocytopenic purpura (ITP). Both in ITP and in secondary
      thrombocytopenia (STP), PBIgG1 and PBIgG3 were found more frequently (60% and
      61%, respectively) than PBIgG2 and PBIgG4 (13% and 9%, respectively). There was
      no relation between the amount of total PBIgG or PBIgM and the platelet count in
      either ITP or STP. Also, if IgG antibodies of only one subclass were found, there
      was no relation between the severity of the thrombocytopenia and the amount of
      PBIgG. By applying the MARIA, it is possible to quantify PBIgG, all four PBIgG
      subclasses and PBIgM in ITP and STP in a reliable way.

PMID- 1998603
TI  - Frequency of sister chromatid exchange and chromosomal aberrations in asbestos
      cement workers.
AB  - Exposure to asbestos minerals has been associated with a wide variety of adverse
      health effects including lung cancer, pleural mesothelioma, and cancer of other
      organs. It was shown previously that asbestos samples collected from a local
      asbestos factory enhanced sister chromatid exchanges (SCEs) and chromosomal
      aberrations in vitro using human lymphocytes. In the present study, 22 workers
      from the same factory and 12 controls were further investigated. Controls were
      matched for age, sex, and socioeconomic state. The peripheral blood lymphocytes
      were cultured and harvested at 48 hours for studies of chromosomal aberrations
      and at 72 hours for SCE frequency determinations. Asbestos workers had a raised
      mean SCE rate and increased numbers of chromosomal aberrations compared with a
      control population. Most of the chromosomal aberrations were chromatid gap and
      break types.

PMID- 1998604
TI  - Blood and urine concentrations of aluminium among workers exposed to aluminium
      flake powders.
AB  - In a group of workers exposed to aluminium flake powders, blood and urine
      concentrations of aluminium were assessed before and after vacation. Another
      group was investigated after retirement. Workers currently exposed to aluminium
      flake powders had urinary concentrations of the metal 80-90 times higher than
      those in occupationally non-exposed referents. The calculated half life for
      concentrations of aluminium in urine was five to six weeks based on four to five
      weeks of non-exposure. Among the retired workers the half lives varied from less
      than one up to eight years and were related to the number of years since
      retirement. These results indicate that aluminium is retained and stored in
      several compartments of the body and eliminated from these compartments at
      different rates.

PMID- 1998605
TI  - Respiratory problems among cotton textile mill workers in Ethiopia.
AB  - This study was conducted to investigate the prevalence of respiratory problems,
      in particular byssinosis, and to explore factors associated with their occurrence
      among a group of 595 randomly selected workers representing 40.5% of those
      exposed to dusty operations in a typical Ethiopian cotton textile mill. A
      standard questionnaire on respiration was administered and pre and postshift
      forced vital capacity (FVC) and forced expiratory volume in one second (FEV1)
      were determined for each worker; workers found to have byssinosis and other
      respiratory diseases were compared with workers having no respiratory diseases in
      terms of the level and duration of exposure to cotton dust and other variables.
      Multiple area air samples from different sections were analysed for elutriated
      cotton dust concentrations (0.86-3.52 mg/m3). The prevalence of byssinosis was
      43.2% among blowers and 37.5% in carders in comparison with four to 24% among
      workers in other sections. Prevalence of chronic bronchitis ranged from 17.6 to
      47.7% and bronchial asthma from 8.5 to 20.5% across all sections. Significant
      across shift decrements in FEV1 and FVC were seen in those workers with
      respiratory tract diseases compared with those workers without such diseases. A
      significant dose response relation for pulmonary function and respiratory
      illnesses was also found by regression analysis. Preventive measures are
      proposed. Further research including a nationwide survey of textile mills is
      suggested. This is the first epidemiological study of the textile industry in
      Ethiopia.

PMID- 1998606
TI  - Mortality from lung cancer among Sardinian patients with silicosis.
AB  - The mortality of 724 subjects with silicosis, first diagnosed in 1964-70 in the
      Sardinia region of Italy, was followed up through to 31 December 1987. Smoking,
      occupational history, chest x ray films, and data on lung function were available
      from clinical records for each member of the cohort. The overall cohort accounted
      for 10,956.5 person-years. The standardised mortality ratios (SMRs) for selected
      causes of death (International Classification of Diseases (ICD) eighth revision)
      were based on the age specific regional death rates for each calendar year. An
      excess of deaths for all causes (SMR = 1.40) was found, mainly due to chronic
      obstructive lung disease, silicosis, and tuberculosis with an upward trend of the
      SMR with increasing severity of the International Labour Office (ILO)
      radiological categories. Twenty two subjects died from lung cancer (SMR = 1.29,
      95% confidence interval (95% CI) = 0.8-2.0). The risk increased after a 10 and 15
      year latency but the SMR never reached statistical significance. No correlation
      was found between lung cancer and severity of the radiological category, the type
      of silica (coal or metalliferous mines, quarries etc), or the degree of exposure
      to silica dust. A significant excess of deaths from lung cancer was found among
      heavy smokers (SMR = 4.11) and subjects with airflow obstruction (SMR = 2.83). A
      nested case-control study was planned to investigate whether the association
      between lung cancer and airway obstruction was due to confounding by smoking. No
      association was found with the ILO categories of silicosis or the estimated
      cumulative exposure to silica. The risk estimate for lung cancer by airflow
      obstruction after adjusting by cigarette consumption was 2.86 for a mild
      impairment and 7.23 for a severe obstruction. The results do not show any clear
      association between exposure to silica, severity of silicosis, and mortality from
      lung cancer. Other environmental or individual factors may act as confounders in
      the association between silicosis and lung cancer. Among them, attention should
      be given to chronic airways obstruction as an independent risk factor for lung
      cancer in patients with silicosis.

PMID- 1998607
TI  - Mortality of coke plant workers in The Netherlands.
AB  - During the production of coke, large quantities of coke oven gas are emitted.
      People who work on the top or on the sides of coke ovens are exposed to this oven
      gas, which contains a range of carcinogenic chemicals. To investigate the cancer
      risks under these work conditions, a retrospective study was undertaken. In total
      11,399 former workers were enrolled in the study. Of these, 5639 had worked in
      the coke plant for at least six months between 1945 and 1969. The other 5740 had
      worked in another plant during the same period and formed a non-exposed group for
      comparison. The study group was followed up until 1984 for mortality. The causes
      of death were obtained from the Central Bureau of Statistics. Among the coke oven
      workers significantly higher death rates were found for lung cancer and non
      malignant respiratory disease. Mortality in the byproduct section was similar to
      that expected. Among workers in the tar distillery the rate for lung cancer was
      higher than expected. The risk for gastric cancer and non-malignant respiratory
      disease among the workers of the coke shipping department was increased but the
      SMRs did not reach statistical significance. No data were collected about
      individual smoking habits or socioeconomic state of the study subjects and the
      possibility that the risk found could be attributed to these factors cannot be
      ruled out. It has been stated by other investigators, however, that the effect of
      not controlling for smoking tends to be modest.

PMID- 1998609
TI  - Mortality and disability among cotton mill workers.

PMID- 1998608
TI  - Bronchiolitis in a patient with talcosis.

PMID- 1998610
TI  - Asbestos related malignancy and the Cairns hypothesis.

PMID- 1998611
TI  - An epidemiological study on occupational acute pyrethroid poisoning in cotton
      farmers.
AB  - A cross sectional survey on the prevalence of acute pyrethroid poisoning in
      cotton farmers was conducted in 1987 and 1988. A total of 3113 pyrethroid
      spraymen (2230 men (71.6%) and 883 women (28.4%] were interviewed after spraying
      and followed up for 72 hours. Adverse effects of pyrethroid exposure were found
      in 834 of them (26.8%) manifested as abnormal facial sensations, dizziness,
      headache, fatigue, nausea, or loss of appetite. Only 10 subjects, who developed
      significant systemic symptoms and had signs of listlessness or muscular
      fasciculation, were diagnosed as having mild occupational acute pyrethroid
      poisoning with a prevalence of 0.31% in subjects exposed to pure pyrethroids and
      0.38% in subjects exposed to pyrethroid organophosphate mixtures. Measurements of
      pyrethroid concentrations in the air of the breathing zone, in skin pads, and in
      urine samples showed that dermal contamination is the main route of exposure to
      pyrethroids in cotton growers. Preventive measures are recommended.

PMID- 1998612
TI  - Levels of exposure and biological monitoring of pyrethroids in spraymen.
AB  - To assess the exposure response relation of pyrethroids in spraymen, 50 adult
      male cotton growers were selected and divided into three groups, one group to
      spray pyrethroids for one day, two groups to spray for three days. Deltamethrin,
      fenvalerate, and a deltamethrin methamidophos mixture were sprayed by appropriate
      subgroups for five hours a day. Exposure levels were evaluated by measuring the
      air concentration, dermal exposure concentration, and urinary content of
      pyrethroids by gas chromatography. Air concentrations of deltamethrin at the
      breathing zone were 0.01-0.89 microgram/m3 in the deltamethrin exposed group. For
      fenvalerate, air concentrations were 0.06-1.98 micrograms/m3. Dermal exposure,
      particularly on the legs, feet, and hands was appreciable and indicated that this
      was the main route of absorption. In those spraying for one day, urinary
      deltamethrin was not detectable by 12 hours after the beginning of exposure
      whereas fenvalerate was still detectable up to 24 hours after first exposure.
      Both pyrethroids could be detected two days after the end of three day spraying.
      Health effects were investigated by interview and physical examination. Twenty
      nine spraymen complained of abnormal facial sensations that developed mostly two
      to three hours from the start of pyrethroid spraying and that disappeared by 24
      hours after exposure ceased. Some had dizziness, headache, and nausea, but no
      subject was diagnosed as having acute pyrethroid poisoning. The symptoms showed
      no significant correlation with urinary pyrethroid excretion. Blood
      cholinesterase activity of spraymen using the pyrethroid methamidophos mixture
      did not change.

PMID- 1998613
TI  - Nerve function in workers with long term exposure to trichloroethene.
AB  - Certain functions of the nervous system were examined in 31 printing workers
      (mean age 44) exposed to trichloroethene (mean duration 16 years) and 28 controls
      (mean age 45). In the sural nerve the conduction velocity (SNCV), response
      amplitude, and refractory period (SRP) were measured. The latencies of the
      masseter and the blink reflex were determined to test the trigeminal nerve. In
      the peroneal nerve the conduction velocity of fast and slow nerve fibres, the
      response amplitude, and the refractory period were determined. As a measure of
      autonomic nerve function the response of the heart rate was determined to
      isometric muscle contraction and deep breathing. Individual cumulative exposure
      was calculated on the basis of exposure levels in the past. The mean cumulative
      exposure of the exposed workers was 704 ppm x years. For the assessment of the
      exposure effect relation a multiple linear regression model was used. A slight
      reduction (-1.1 m/s) in the SNCV was found and a prolongation (0.4 ms) of the SRP
      (mean of the controls 1.95 ms). The latency of the masseter reflex (mean 10.4 ms)
      had increased (0.4 ms). With respect to the blink reflex no prolongation was
      found. No impairment was found in the functions of motor and autonomic nerves.
      This study shows that the refractory period may be a sensitive indicator of
      preclinical toxic neuropathies. Long term exposure to trichloroethene at
      threshold limit values (about 35 ppm) may slightly affect the trigeminal and
      sural nerves.

PMID- 1998614
TI  - Experimental and human studies on antimony metabolism: their relevance for the
      biological monitoring of workers exposed to inorganic antimony.
AB  - Unlike inorganic arsenic, inorganic trivalent antimony (Sb) is not methylated in
      vivo. It is excreted in the bile after conjugation with glutathione and also in
      urine. A significant proportion of that excreted in bile undergoes an
      enterohepatic circulation. In workers exposed to pentavalent Sb, the urinary Sb
      excretion is related to the intensity of exposure. It has been estimated that
      after eight hours exposure to 500 micrograms Sb/m3, the increase of urinary Sb
      concentration at the end of the shift amounts on average to 35 micrograms/g
      creatinine.

PMID- 1998615
TI  - A cytogenetic study of men occupationally exposed to uranium.
AB  - Blood lymphocyte cultures from two groups of workers occupationally exposed to
      uranium were examined for asymmetrical chromosome aberrations and sister
      chromatid exchanges (SCEs). Significant increases in both cytogenetic endpoints
      were seen. For dicentrics this appeared to be particularly associated with
      exposure to soluble uranium. The external radiation exposure experienced by these
      men was insufficient to explain the increase in dicentrics, and irradiation of
      lymphocytes by internally deposited uranium would have been minimal. As the SCEs
      were also raised, the genotoxic effect is likely to be due to the chemical nature
      of the compound. The increase in frequency of dicentrics associated with smoking
      was greatest in the group with exposure to soluble uranium suggesting some
      interaction between the two clastogens. No such interactive effect was seen for
      SCE frequencies, in which increases attributable to smoking were similar in the
      worker and control groups.

PMID- 1998616
TI  - External cephalic version at term: how high are the stakes?

PMID- 1998617
TI  - A modified contraceptive diaphragm for relief of uretero-vaginal fistula. Case
      report.

PMID- 1998618
TI  - The clinical presentation of women with human immunodeficiency virus infection.

PMID- 1998620
TI  - Certain dates may not provide a reliable estimate of gestational age.

PMID- 1998619
TI  - Neutrophil activation in small for gestational age pregnancies.

PMID- 1998621
TI  - Late recurrence of a congenital diaphragmatic hernia. Case report.

PMID- 1998622
TI  - Darier's disease localized to the vulva.

PMID- 1998623
TI  - The effect of caput succedaneum on oxygen saturation measurements.

PMID- 1998624
TI  - Use of Gynocheck endometrial tissue sampler in infertility.

PMID- 1998625
TI  - Autoimmune ovarian failure with elevated serum levels of luteinizing hormone and
      enlarged ovaries.

PMID- 1998626
TI  - Effective destruction of cervical intraepithelial neoplasia (CIN) 3 at 100
      degrees C using the Semm cold coagulator: 14 years experience.
AB  - A total of 1628 women with CIN 3 treated with the Semm cold coagulator between
      1975 and 1989 was followed primarily by cytology. The standard suitability
      criteria for ablation were adhered to except that patients were treated at their
      first visit when the colposcopist expected that the diagnosis would be no worse
      than CIN 3. Overall 97% of the women were treated at their first visit. In 30
      women (2%) the histology was glandular or worse than expected, but 22 of these
      showed no persistent cervical disease subsequently. Follow-up was achieved for
      87% at 10 years. In actuarial terms the primary success rate was 95% at 1 year
      and 92% at 5 years, it was similar for all age groups. Repeat cold-coagulation
      for persistent/recurrent CIN 3 was less successful and is not advised. The
      outcome for 226 pregnancies established after treatment is known. The rates for
      miscarriage, preterm or operative delivery were not increased. Cold-coagulation
      of CIN 3 at 100 degrees C as performed by us is as effective as any other
      treatment and calls into question the need for more expensive practices.

PMID- 1998627
TI  - A randomized control trial of two cervical spatulas.
AB  - The sampling efficacy of the Ayre and Rocket cervical spatulas was compared in a
      randomized controlled trial involving 533 women who were attending a colposcopy
      clinic either for investigation of cytological abnormality or for review after
      treatment of CIN. Smears were compared with respect to the presence of
      cytological abnormality and two types of normal cervical epithelial cells
      (endocervical and immature metaplastic cells) which are considered indicators of
      adequate cytological sampling. Smears taken with the Rocket spatula were
      significantly less likely to contain immature metaplastic cells (95% CI on
      difference in proportion; 5-30%), but more likely to contain endocervical cells
      (95% CI 16-36%). No significant difference was found in the proportion of smears
      containing one or other type of indicator cell or in the yield of abnormal
      smears. It is concluded that the Rocket spatula offered no advantage when used in
      these circumstances. This study illustrates how spurious conclusions of sampling
      efficacy can be drawn if only one type of indicator cell is used as an endpoint.

PMID- 1998628
TI  - Vaginal epithelial abnormalities in patients with CIN: clinical and pathological
      features and management.
AB  - Of 4147 women who had CIN treated by laser at the Regional Gynaecological
      Oncology Centre, Queen Elizabeth Hospital, Gateshead, 103 (2.5%) had co-existing
      vaginal epithelial abnormalities. CIN 3 was the histological diagnosis most often
      associated with vaginal lesions. The upper vagina was almost always involved. In
      67% the lesion in the cervix appeared to be confluent with that in the vagina.
      Even when the lesions were confluent, biopsies form the cervical and vaginal
      components did not always show the same grade of intraepithelial neoplasia and in
      some biopsies they showed different lesions. Laser treatment appears to be
      effective for the vaginal lesions and is therefore recommended although, in
      selected patients, careful follow up alone may suffice.

PMID- 1998629
TI  - The treatment of CIN: do we need lasers?

PMID- 1998630
TI  - Fetal monitoring with pulse oximetry.
AB  - Continuous fetal monitoring was achieved with a fetal scalp pulse oximetry sensor
      in 86 labours. The average recorded fetal oxygen saturation in early labour
      (cervical dilatation less than 5 cm) was 68% (SD 13%). At the end of labour
      (cervical dilatation greater than or equal to 9 cm) the recorded mean oxygen
      saturation was 58% (SD 17%). The largest range of readings during a single labour
      was 81%-11% but this drop was associated with cord compression. The average SD
      during 1 h of normal labour was 10%. A second group of 40 fetuses was monitored
      during induction of labour before and after elective amniotomy. Oxygen saturation
      did not appear to change after amniotomy (mean change -0.4%, SD 1.2%) and there
      was no difference between mean antenatal or early intrapartum readings. We
      excluded the amniochorionic membranes as a possible source of data corruption by
      measuring their in vitro absorption spectra and confirming that they do not
      preferentially absorb light of either 660 or 940 nm wavelength. Non-invasive
      pulse oximetry can be used to monitor the fetus before and during labour.

PMID- 1998632
TI  - Fetal crown-rump length values in the first trimester based upon ovulation timing
      using the luteinizing hormone surge.
AB  - Fetal crown rump length (CRL) was measured weekly in 33 singleton pregnancies
      that were established after in vitro fertilization, gamete intrafallopian
      transfer or natural intercourse in monitored infertility treatment cycles. The
      time of the luteinizing hormone surge or hCG administration was known for all of
      them. There was no difference in CRL between the different infertility treatment
      groups. CRL measurements from this and a similar study where gestational age had
      been based on the time of ovulation were compared with the CRL measurements from
      pregnancies where the gestational age had been calculated from the last menstrual
      period. The CRL was found to be generally smaller in the studies based on
      ovulation timing and the difference was statistically significant at one time
      point. This suggests that there is a need for a gold standard in obstetric
      ultrasound, measurements being based on the gestational age as calculated from
      the unequivocal date of conception, rather than the last menstrual period.

PMID- 1998631
TI  - Coagulation studies in the syndrome of haemolysis, elevated liver enzymes and low
      platelets.
AB  - The presence of disseminated intravascular coagulation (DIC) in the syndrome of
      haemolysis, elevated liver enzymes and low platelets (HELLP) is debated. We
      assessed the occurrence of decompensated and compensated DIC (using predefined
      criteria) in 15 consecutive nulliparous pregnant patients with gestational
      hypertension combined with the HELLP syndrome and in 12 consecutive nulliparous
      controls with pregnancy induced hypertension (PIH) but without the HELLP
      syndrome. A combination of routine coagulation assays revealed the absence of
      decompensated DIC in all studied patients. However, using more specific and
      sensitive coagulation assays, compensated DIC was observed in all HELLP patients
      and in three patients in the control group. The mean values of antithrombin III,
      thrombin-antithrombin III complexes and protein C in the HELLP and the control
      group were 66 vs 87% (P = 0.0004), 21 vs 8 ng/ml (P = 0.0008) and 57 vs 90% (P =
      0.0018) respectively. We conclude that HELLP patients show evidence of
      compensated DIC which may have pathophysiological significance for the observed
      organ damage.

PMID- 1998633
TI  - Babies born before arrival at hospital.
AB  - OBJECTIVE: To establish the prevalence of babies born before arrival at two local
      hospitals. To identify women at risk of giving birth before arrival, and the
      morbidity and mortality associated with such births. DESIGN: A case control
      study. Each baby born before arrival and its mother were compared with the next
      born in the hospital (random control), and one matched for gestation and
      birthweight, together with their mothers. SETTING: Two maternity units serving
      East Birmingham and Solihull. SUBJECTS: All babies (and their mothers) born
      before arrival at these hospitals from January 1983 to December 1987. MAIN
      OUTCOME MEASURES: Perinatal mortality rates, patterns of perinatal morbidity,
      demographic, social and obstetric features of the mothers. RESULTS: 137 (0.44%)
      of 31,140 consecutive births were before arrival at hospital (BBA group). The
      perinatal mortality rate in the BBA group was 58.4/1000 (8 deaths) compared with
      10.1/1000 for all inborn babies (relative risk 5.8, 95% confidence interval 2.9
      11.4). In the BBA group the mean birthweight of 3008 g was 212 g (95% CI 50-374
      g) less than that in the random control group; the mean gestation of 266 days was
      10 days less (95% CI 5.9-14.1 days) than in the random control group. Hypothermia
      was the commonest morbidity. Women delivered before arrival tended to be either
      multigravid inner city Asians living a long way from the hospital or unmarried
      unbooked younger white Europeans. CONCLUSIONS: The high perinatal mortality was
      related to immaturity and low birthweight, rather than to birth before arrival
      itself. Although groups of mothers at risk of delivery before arrival can be
      identified more information is needed to establish whether additional antenatal
      care would be beneficial for these women and their babies.

PMID- 1998634
TI  - What constitutes an adequate cervical smear?

PMID- 1998635
TI  - Smoking during pregnancy: a significant cause of neonatal thyroid enlargement.
AB  - The influence of maternal smoking during pregnancy on the function and the
      echographic volume of the neonatal thyroid gland was examined in an area of
      borderline iodine intake (median maternal urinary iodine: 315 range 79-1558
      nmol/l). There was a positive correlation (P less than 0.001) between cord serum
      thiocyanate (SCN) concentrations used as an index of maternal smoking and the
      maternal smoking habits. The thyroid volume/birthweight ratio increased
      significantly as a function of SCN values (P less than 0.005): this increase was
      secondary to a decrease in birthweight as well as to an increase in thyroid
      volume. There was also a positive correlation between cord serum thyroglobulin
      (Tg) and SCN levels (P = 0.001). Serum thyroid-stimulating hormone (TSH) and free
      thyroxine (FT4) values remained within the normal range for age in all newborn
      infants and were not significantly correlated with SCN values. These results show
      that smoking during pregnancy in areas with borderline iodine intake may be a
      significant cause of thyroid enlargement in the newborn.

PMID- 1998636
TI  - Distal urethral electrical conductance (DUEC)--a preliminary assessment of its
      role as a quick screening test for incontinent women.
AB  - Measurement of distal urethral electrical conductance (DUEC) has been used to
      detect the movement of urine along the distal urethra. DUEC was used as a
      screening test in 100 women attending the urodynamic clinic with incontinence and
      in the 33 women who voided over 250 ml, the findings correlated well with
      subsequent urodynamic diagnosis of urethral sphincter incompetence and detrusor
      instability.

PMID- 1998637
TI  - External cephalic version at term. A randomized controlled trial using tocolysis.
AB  - OBJECTIVE: To assess the role of external cephalic version (ECV) at term, using
      tocolysis. DESIGN: A randomized controlled trial over a 12 month period. SETTING:
      Harare Maternity Hospital, Harare, Zimbabwe. SUBJECTS: 208 women with breech
      presentation at term were recruited after satisfying eligibility criteria. There
      were 103 women in the study group and 105 in the control group. At the end of the
      study a further 104 women were recruited for ECV. INTERVENTION: ECV attempted
      after intravenous injection of 10 micrograms of hexaprenaline, using either
      forward or backward somersault over a maximum period of 5 min. MAIN OUTCOME
      MEASURES: Success rate in terms of presentation during labour, need for caesarean
      section, and various variables related to fetal outcome. RESULTS: ECV reduced the
      frequency of breech presentation during labour from 83% to 17% and that of
      caesarean section from 33% to 13%. There were no troublesome complications from
      the procedure. CONCLUSION: In carefully selected women with breech presentation,
      ECV at term using tocolysis, safely reduced the rate of breech presentation in
      labour and also the caesarean section rate. Further research is needed to
      determine the role of ECV in early labour.

PMID- 1998638
TI  - A randomized controlled trial of early amniotomy.
AB  - OBJECTIVE-To determine if a policy of early amniotomy resulted in a reduction in
      mean labour duration when compared to a policy of conservation of the membranes.
      DESIGN-A single-centre randomized controlled trial. SETTING-A tertiary care
      teaching hospital in Alberta, Canada. SUBJECTS-Ninety-seven term nulliparae in
      spontaneous labour, baby in cephalic presentation. INTERVENTION-Early amniotomy
      versus intent to keep membranes intact. MAIN OUTCOME MEASURES-Interval from
      randomization to delivery, rate of abnormalities of fetal heart rate tracings,
      cord artery blood pH, Apgar scores. RESULTS-The mean interval from randomization
      to delivery was 390.9 (SE 29.1) min in the amniotomy group and 442.9 (SE 34.1)
      min in the control group (P = 0.251). There were no differences between groups in
      the occurrence of fetal heart rate tracing abnormalities, nor was there a
      difference in the proportion of babies with abnormal Apgar scores, or abnormal
      cord pH (less than 7.20). CONCLUSION-The results of the study fail to support the
      long held belief that early amniotomy is an effective method for reducing labour
      duration.

PMID- 1998639
TI  - Growth hormone excess and galactorrhoea without acromegalic features. Case
      reports.

PMID- 1998640
TI  - Quantification of fibrin deposition in flowing blood with peroxidase-labeled
      fibrinogen. High shear rates induce decreased fibrin deposition and appearance of
      fibrin monomers.
AB  - To study fibrin incorporation into thrombi at different wall shear rates, a new
      method to study fibrin deposition on extracellular matrixes underlying stimulated
      endothelial cells under flow conditions was developed. For this method, we used
      fibrinogen labeled with peroxidase (Fg-PO). Fg-PO was fully exchangeable for Fg
      in the clotting assays tested, and PO activity was bound to fibrin-specific
      fragments. Fg-PO containing fibrin could be stained for microscopic studies with
      3,3'-diaminobenzidine and could be quantified by oxidation of phenylenediamine.
      The absorbance values at 492 nm were converted to fibrin quantities via a
      standard curve. To study fibrin deposition, Fg-PO was added in trace amounts to
      whole blood anticoagulated with low-molecular-weight heparin, and perfusion
      studies were performed over endothelial cell matrixes containing tissue factor.
      In parallel perfusion studies, 125I-labeled Fg was added in trace amounts to
      whole blood instead of Fg-PO. Both quantitative methods demonstrated decreased
      fibrin deposition after perfusions at 1,300 sec-1 compared with fibrin deposition
      after perfusions at 300 sec-1, while fibrinopeptide A generation was independent
      of the wall shear rate. The decrease in fibrin deposition at 1,300 sec-1 was
      accompanied by the appearance of fibrin monomers in the perfusate. This suggested
      that the decrease in fibrin incorporation at 1,300 sec-1 was due to the impaired
      polymerization of fibrin monomers. This impairment was probably due to a decrease
      in local fibrin monomer concentration as a result of the increased removal of
      monomers from the surface at 1,300 sec-1.

PMID- 1998641
TI  - Cholesterol accumulation in J774 macrophages induced by triglyceride-rich
      lipoproteins. Comparison of very low density lipoprotein from subjects with type
      III, IV, and V hyperlipoproteinemias.
AB  - The capacity of human triglyceride-rich lipoproteins to induce cholesterol
      accumulation in the murine J774 macrophage cell line was investigated with large
      very low density lipoprotein (VLDL, Sf 60-400) obtained from subjects with type
      III, IV, and V hyperlipoproteinemias. After incubation for 24 hours, VLDLs from
      type IV and type V subjects were similar in their ability to raise cellular
      cholesterol deposition threefold to fourfold and cellular triglyceride 16-fold.
      The increase in cholesterol was entirely due to the dramatic increase in
      cholesterol ester, from less than 1 to greater than 50 micrograms/mg cell
      protein. Total cholesterol accumulation was fourfold to fivefold greater than the
      cholesterol accumulation observed for VLDL or low density lipoprotein (LDL) from
      normal subjects. Cholesterol esterification (acyl coenzyme A: cholesterol
      acyltransferase [ACAT] activity) paralleled the rate of cholesterol accumulation
      in these cells. Treating the macrophages with the ACAT inhibitor 58035, which is
      known to downregulate the LDL receptor in these cells, diminished cholesterol
      accumulation by 40% for type IV VLDL and by 23% for normal LDL. Since
      hypertriglyceridemic VLDL carries excess apoprotein (apo) E molecules, we
      investigated the role of normal and abnormal apo E. An anti-apo E monoclonal
      antibody, known to block the binding of apo E to the LDL receptor, blocked type
      IV VLDL-induced cholesterol ester accumulation by approximately 70%. In contrast
      to type IV subjects, VLDL from type III subjects (homozygous for apo E2) when
      incubated with J774 macrophages (which do not secrete apo E) caused only a modest
      1.5-2-fold increase in cellular cholesterol. Pre-beta- and beta-migrating VLDL
      subfractions from type III subjects were equally ineffective in causing
      cholesterol accumulation. By contrast, beta-VLDL from cholesterol-fed rabbits
      caused a sevenfold to eightfold increase in cellular cholesterol content. These
      results indicate that triglyceride-rich lipoproteins from type IV and type V
      subjects can cause substantial cholesterol ester accumulation and enhanced
      cholesterol esterification in J774 cells. The lower cholesterol accumulation with
      type IV VLDL in the presence of apo E antibodies and VLDL from type III subjects
      demonstrates the importance of functional apo E in this process.

PMID- 1998642
TI  - Characterization of three mutations of the low density lipoprotein receptor gene
      in Italian patients with familial hypercholesterolemia.
AB  - Three gross rearrangements of the low density lipoprotein receptor (LDL-R) gene
      were recognized during a survey of 23 unrelated Italian subjects with familial
      hypercholesterolemia (FH). Restriction endonuclease data were obtained by
      Southern blotting and hybridization with exon-specific probes. Proband FH-29 is
      heterozygous for a 4-kb deletion, which eliminates exons 13 and 14. This mutation
      is similar to that previously reported by other investigators in one Italian
      homozygous and two British and Canadian heterozygous patients. Proband FH-30 is
      homozygous for a 5.5-kb insertion caused by a duplication of exons 16 and 17 of
      the LDL-R gene. LDL-R mRNA isolated from skin fibroblasts of FH-30 was found to
      be larger than normal mRNA (5.6 versus 5.3 kb), in concordance with the insertion
      of the 236 nucleotides corresponding to exons 16 and 17. Proband FH-44 was found
      to have greater than 25-kb deletion, which eliminates the first six exons and the
      promoter region of the gene. This is the first example of a deletion that
      eliminates the promoter as well as the ligand-binding domain of the LDL-R gene.
      In the skin fibroblasts of this patient, the level of LDL-R mRNA was
      approximately half that found in control fibroblasts. We designate the new
      mutations found in FH-30 and FH-44 as FHviterbo and FHBologna-1, respectively,
      after the names of the Italian cities where the two patients were born.

PMID- 1998643
TI  - Modulation of actin isoform expression in cultured arterial smooth muscle cells
      by heparin and culture conditions.
AB  - Heparin inhibits arterial smooth muscle cell (SMC) proliferation in vivo and in
      vitro; moreover, it reinduces the expression of alpha-smooth muscle (SM) actin
      (an accepted marker of SMC differentiation) in SMCs of the intimal thickening
      that develops after experimentally induced endothelial lesions. We have
      investigated the effect of heparin on the proliferation and actin isoform
      expression in cultured rat SMCs. In the presence of 10% fetal calf serum (FCS),
      heparin-treated primary and passage 5 SMCs showed a decrease of proliferation and
      an increase of alpha-SM actin (measured by Western blots or two-dimensional gel
      electrophoresis) compared with untreated SMCs. When SMCs were cultured in the
      presence of 10% plasma-derived serum, no proliferation occurred and heparin did
      not modify alpha-SM actin expression. This suggests that the action of heparin is
      related to its antiproliferative activity. SMCs cultured in the presence of 10%
      FCS plus heparin had the same level of proliferation as SMCs cultured in 5% FCS
      but had a higher content of alpha-SM actin. SMCs cultured in 20% rat whole-blood
      serum had a proliferation similar to that observed in SMCs cultured in 10% FCS
      but had a higher content of alpha-SM actin. Moreover, in SMCs cultured in 20%
      whole-blood serum, heparin inhibited SMC proliferation but did not modify alpha
      SM actin expression. Thus, the action of heparin on alpha-SM actin expression
      appears to be partially independent of proliferation and is related to culture
      conditions. The proportion of alpha-SM actin mRNA, as measured by Northern blots
      with an alpha-SM actin mRNA-specific probe, was increased by heparin compared
      with cells cultured in 10% FCS; this suggests that heparin acts at the
      transcriptional or posttranscriptional level. Our results show that heparin acts
      not only on SMC proliferation but also on SMC differentiation; further
      investigation along these lines may help in the understanding of the mechanisms
      of SMC adaptation during normal and pathological conditions.

PMID- 1998644
TI  - Display of low density lipoprotein receptors is clustered, not dispersed, in
      fibroblast and hepatocyte plasma membranes.
AB  - Although the principal details of low density lipoprotein (LDL) uptake by
      receptor-mediated endocytosis and its subsequent intracellular fate have been
      thoroughly investigated, an aspect of this mechanism that continues to provoke
      controversy concerns the manner of display of LDL receptors upon their initial
      insertion at the cell surface. While our studies based on electron microscopy of
      platinum/carbon replicas of gold-labeled cells have previously suggested a
      clustered display pattern, others have concluded, before and since, that LDL
      receptors are inserted individually at random widely dispersed sites in the
      plasma membrane. In this article, we present a series of experiments designed to
      discriminate between these competing hypotheses. In addition to the use of LDL
      colloidal gold complexes, visualized electron microscopically, on cells subjected
      to a variety of experimental procedures, these experiments include the
      application of anti-apolipoprotein B-100 antibodies, anti-LDL-receptor
      antibodies, and direct visualization of native (unlabeled) LDL molecules at the
      cell surface. All results point to a loose-cluster arrangement, not one involving
      widely dispersed individual units, as the initial display pattern of newly
      inserted LDL receptors. A comparison of LDL and beta-very low density lipoprotein
      receptor distribution in fibroblasts and hepatocytes suggests that this cluster
      pattern is a characteristic of the LDL (apolipoprotein B/E) receptor across cell
      types, but that the closely related apolipoprotein E receptor differs in that it
      is inserted individually in a highly dispersed state, in common with a variety of
      other receptor types.

PMID- 1998645
TI  - Apolipoprotein E polymorphism association with lipoprotein profile in endogenous
      hypertriglyceridemia and familial hypercholesterolemia.
AB  - Apolipoprotein (apo) E polymorphism was among the first-reported genetic
      polymorphisms that explained part of the normal variation in plasma cholesterol
      concentrations in humans. The aim of this study was to assess the influence of
      allelic variation at the apo E gene locus on the plasma lipoprotein profile in
      hyperlipidemia. The lipoprotein levels of hyperlipidemic subjects of the major
      apo E phenotypes (E3/2, E3/3, and E4/3) were compared. One hundred eighty-two
      subjects with endogenous hypertriglyceridemia and 98 subjects with familial
      hypercholesterolemia due to a 10-kb deletion in their low density lipoprotein
      (LDL) receptor genes were compared with 424 normolipidemic controls from the same
      environmental background. LDL concentrations were lower in the E3/2 subset than
      in the E3/3 or E4/3 subset in the control, hypertriglyceridemic, and familial
      hypercholesterolemic groups. In absolute values, the magnitude of the effect was
      greatest in the familial hypercholesterolemic group. However, the direction and
      percentage change were identical in the presence or absence of the LDL receptor
      defect, indicating that the apo E phenotype effect is independent of LDL receptor
      status. Triglyceride and very low density lipoprotein (VLDL) cholesterol
      concentrations were higher in E3/2 than in E3/3 or E4/3 hypertriglyceridemic
      subjects, but this difference was not found in the familial hypercholesterolemic
      or control group. Thus, there seems to be a specific interaction between apo E
      isoforms and VLDL metabolism in hypertriglyceridemia; allelic variation at the
      apo E gene locus seems to be associated with specific alterations in the plasma
      lipoprotein profile of subjects with well-defined types of hyperlipidemia.

PMID- 1998646
TI  - Genetic and environmental factors affecting the incidence of coronary artery
      disease in heterozygous familial hypercholesterolemia.
AB  - This study explores the influence of selected genetic and environmental factors
      on the clinical expression of heterozygous familial hypercholesterolemia (FH). A
      detailed examination of the physical and biochemical features of FH was performed
      in a large cohort of 208 females and 156 males. Females with FH had higher levels
      of total, low density lipoprotein (LDL), and high density lipoprotein (HDL)
      cholesterol when compared with males, although the concentration of HDL
      cholesterol was significantly lower for both sexes when compared with normals.
      The reported incidence of coronary artery disease (CAD) was 31% for men and 13%
      for women, which was lower when compared with figures from previous studies. The
      average age of onset of coronary symptoms was delayed in females, with a mean age
      of 55 years compared with 48 years for males (p less than 0.05). A greater risk
      of developing CAD in men was associated with lower levels of HDL cholesterol and
      a history of smoking. In women, however, CAD was associated with elevated
      triglycerides and the presence of hypertension. The frequencies of the epsilon 2,
      epsilon 3, and epsilon 4 alleles of apolipoprotein E in 125 unrelated FH subjects
      did not differ significantly from the normal population. In addition, there was
      no apparent relation between apo E4 and the concentration of any of the
      parameters in the plasma lipid profile; however, the presence of the E2 isoform
      was associated with significantly elevated triglycerides in both sexes. This
      study has allowed us to identify those factors, which, in addition to total
      cholesterol levels, are associated with the development of premature coronary
      atherosclerosis in heterozygous FH.

PMID- 1998647
TI  - Enhanced susceptibility to in vitro oxidation of the dense low density
      lipoprotein subfraction in healthy subjects.
AB  - Oxidative modification of low density lipoprotein (LDL) has been implicated as a
      factor in the generation of macrophage-derived foam cells, the hallmark of
      atherosclerotic plaques. Because LDL consists of discrete subfractions with
      different physicochemical characteristics, the question arises as to whether
      these LDL subfractions differ in their susceptibility to oxidative modification.
      To answer this question, three LDL subfractions, LDL1, LDL2, and LDL3, were
      isolated from the plasmas of 11 healthy volunteers by density gradient
      ultracentrifugation. The LDL subfractions were oxidatively modified by incubation
      with copper ions. Differences in the subfractions' susceptibilities to lipid
      peroxidation were studied by measuring the formation of the 234-nm-absorbing
      oxidation products every 3 minutes on an ultraviolet spectrophotometer. A
      significant inverse linear relation was found between LDL subfractions and lag
      time (regression coefficient = -8.50, p less than 0.001), indicating that both
      the dense LDL3 and the light LDL2 were less well protected against oxidative
      modification than the very light LDL1. The LDL subfractions showed a positive
      linear relation with the rate of oxidation (regression coefficient = 0.46, p less
      than 0.001) and the amount of conjugated dienes formed in the LDL subfractions
      after 4 hours of oxidation (regression coefficient = 9.24, p less than 0.001).
      Thus, both LDL3 and LDL2 were more extensively modified in time than LDL1, which
      may be explained by the significantly higher concentration of polyunsaturated
      fatty acids in LDL3 (micromoles per gram LDL cholesterol) compared with LDL1
      (Tukey's test, p less than 0.05). These results indicate that the more dense LDL
      subfractions, that is, LDL2 and LDL3, are more susceptible to oxidative
      modification and therefore may contribute more to foam cell formation than the
      less dense LDL subfraction LDL1.

PMID- 1998648
TI  - Relation of serum testosterone levels to high density lipoprotein cholesterol and
      other characteristics in men.
AB  - Although levels of high density lipoprotein (HDL) cholesterol in males decrease
      during adolescence and after treatment with testosterone derivatives, several
      studies have reported that levels of HDL cholesterol are positively associated
      with endogenous levels of testosterone in men. This association was further
      examined using data collected during 1985 and 1986 from 3,562 white and 500 black
      men who ranged in age from 31 to 45 years. Black men had higher mean levels of
      both HDL cholesterol (8 mg/dl) and total testosterone (33 ng/dl) than white men,
      and positive associations were observed between testosterone and HDL cholesterol
      levels (r = 0.22, whites; r = 0.26, blacks). In addition, levels of testosterone
      were related positively to alcohol consumption and cigarette smoking and
      negatively to age, Quetelet index, and use of beta-blockers. We used
      stratification and regression analyses to determine if any of these
      characteristics could account for the positive association between levels of HDL
      cholesterol and total testosterone. Although controlling for most factors had
      little influence, adjusting for Quetelet index reduced the strength of the
      association between levels of testosterone and HDL cholesterol by approximately
      30%. These findings suggest that the positive association between levels of
      testosterone and HDL cholesterol may not be causal. Multivariable analyses that
      control for obesity and other potentially confounding characteristics should be
      used in studies that assess the relation of testosterone levels to coronary heart
      disease.

PMID- 1998649
TI  - Autoantibodies against modified low density lipoprotein. Nonlipid factor of blood
      plasma that stimulates foam cell formation.
AB  - The blood serum of patients with coronary atherosclerosis possesses an ability to
      induce the accumulation of cellular lipids in primary cultures of human aortic
      intimal cells. Factors responsible for this property of the atherosclerotic
      patients' sera are represented by modified (desialylated) low density lipoprotein
      (LDL) and a nonlipid factor interacting with LDL. It was assumed that the
      nonlipid factor was antibodies against LDL. Total immunoglobulin G (IgG) fraction
      was isolated from the sera of atherosclerotic patients, and IgGs interacting with
      LDL (anti-LDL) were then purified by affinity chromatography on a sorbent with
      immobilized LDL. From the sera of patients, a 30-fold greater amount of anti-LDL
      has been isolated than from the sera of healthy donors. The affinity constant of
      anti-LDL to the lipoprotein obtained from the blood of healthy donors was 2 x
      10(7) M-1. The affinity of anti-LDL to the lipoprotein from the blood of
      atherosclerotic patients, as well as to LDL desialylated in vitro with
      neuraminidase, was much higher. Anti-LDL increased the uptake of LDL by cultured
      aortic cells by approximately 2.5-fold and substantially increased intracellular
      lipid accumulation. The obtained data suggest that autoantibodies against LDL are
      an essential factor of blood plasma responsible for its atherogenic potential.

PMID- 1998650
TI  - Central adipose distribution is related to coronary atherosclerosis.
AB  - A "male" distribution of adipose tissue in women (excess of fat in the abdomen
      compared with that in the hips; i.e., elevated waist/hip ratio) has been related
      to symptomatic cardiovascular disease. An elevated waist/hip ratio has also been
      related to symptomatic cardiovascular and cerebrovascular diseases in men, as
      well as to risk factors for these diseases and various metabolic conditions. To
      determine whether adipose distribution was related to coronary atherosclerosis,
      we performed a case-control study in patients with angiographically documented
      coronary atherosclerosis (cases) and in angiographically normal hospital and
      neighborhood controls. The data show that distribution of adiposity as assessed
      by waist/hip ratio is significantly related to coronary atherosclerosis in both
      females and males. Waist/hip ratio is significantly greater in female cases
      compared with either control group; in males, waist/hip ratio is significantly
      greater in cases compared with asymptomatic neighborhood controls but not
      compared with patients with normal coronary arteries. These results persist after
      control for age, plasma concentrations of lipids and lipoproteins, body mass
      index, history of hypertension, history of diabetes, and smoking status. The
      connection between the male adipose distribution in females and coronary
      atherosclerosis partly explains the greater likelihood of symptomatic
      cardiovascular disease in them. Males with excess deposition of fat in the
      abdominal region are also likely to experience increased risk.

PMID- 1998651
TI  - Reduction of transmural 125I-albumin concentration in rat aortic media by chronic
      hypertension.
AB  - Relative 125I-albumin concentration was measured in vivo in the aortic media of
      sham-operated (n = 10) and hypertensive (two-kidney, one clip) rats, untreated (n
      = 8) or treated (n = 10) by an angiotensin converting enzyme inhibitor (CEI,
      Trandolapril). Blood pressure was acutely lowered to a normal level at the time
      of the experiment in hypertensive rats (n = 7) to separate the direct effect of
      increased pressure from the effect of pressure-induced structural changes.
      Relative tissue concentration profiles of labeled albumin across the media were
      obtained using a serial frozen-sectioning technique. In hypertensive rats, the
      mean medial albumin concentration decreased by 35% in the ascending arch and 32%
      in the descending arch (p less than 0.01). When blood pressure was acutely
      lowered in hypertensive animals, this value decreased further by 56% in the
      ascending arch, 48% in the descending arch (p less than 0.01), and 22% in the
      thoracic aorta (p less than 0.05) as compared with controls. The medial thickness
      in hypertensive rats was significantly increased (more in the ascending arch than
      in the rest of the aorta). Four-week CEI treatment reversed hypertension and
      medial thickening, but the mean medial albumin concentration remained
      significantly lower in the arch (by 36% in the ascending part and 40% in the
      descending part, p less than 0.01). The collagen content in the thoracic aorta
      was significantly increased in hypertensive rats (by 40%, p less than 0.01) and
      remained increased (by 29%, p less than 0.01) after CEI treatment. These results
      suggested that the hypertension-induced structural changes might reduce the
      medial distribution volume for albumin, whereas elevated blood pressure per se
      tended to enhance albumin concentration within the media. However, the net result
      of chronic hypertension was a reduction of the mean medial albumin concentration.
      The aortic arch appeared to be more affected than the rest of the aorta. Fiber
      content, more than medial thickness, might be responsible for the observed
      differences in albumin concentration. Lowering of blood pressure seemed to be
      insufficient to restore normal albumin concentration profiles and perhaps those
      of other macromolecules. This finding may be relevant in evaluating some of the
      complications associated with hypertension.

PMID- 1998652
TI  - Plasma fibrinogen and ischemic heart disease risk factors.
AB  - The association between risk factors for ischemic heart disease and plasma
      fibrinogen level was analyzed in a cross-sectional population study. All 51-year
      old men living in a certain area within the county of Copenhagen were invited;
      439 of 542 (81%) participated in the study. Data were collected via questionnaire
      and at health examinations. The following independent variables were analyzed:
      social variables, which included social class, marital status, and job strain;
      psychological and psychosomatic variables, which included abdominal pain,
      personal and economic problems, self-assessed state of health, and degree of
      loneliness; behavioral variables, which included smoking, drug consumption,
      physical activity, use of sugar, and alcohol consumption; and physiological
      variables, which included high density lipoprotein (HDL) and low density
      lipoprotein (LDL) cholesterol, physical fitness, fasting glucose level, waist-to
      hip ratio, and systolic blood pressure. In the multivariate analyses, the
      following variables showed an independent positive association with plasma
      fibrinogen level: one social variable (low social class); two psychological
      variables (abdominal pain index and personal/economic problems); two behavioral
      variables (smoking and physical inactivity during leisure time); and three
      physiological variables (low HDL cholesterol, low physical fitness, and high LDL
      cholesterol). The strongest independent associations with plasma fibrinogen level
      were found for smoking, social class, LDL cholesterol, and HDL cholesterol. These
      analyses suggest that smoking is a major risk factor for an elevated plasma
      fibrinogen level, but that other factors such as social class, cholesterol level,
      physical inactivity/physical fitness, and psychological problems also influence
      plasma fibrinogen level.

PMID- 1998653
TI  - Overproduction of a buoyant low density lipoprotein subspecies in spontaneously
      hypercholesterolemic mutant pigs.
AB  - We previously described the hypercholesterolemia of pigs with defined
      apolipoprotein B (apo B) alleles associated with reduced binding of low density
      lipoprotein (LDL) to its receptor in vitro and slow clearance from the
      circulation in vivo. The increased plasma LDL in the hypercholesterolemic pigs
      was confined to a buoyant LDL subspecies. Because of this qualitative change in
      the LDL subspecies profile, we studied the turnover of buoyant and dense LDL
      subspecies independently. Normal and mutant radioiodinated buoyant and dense LDLs
      were simultaneously injected into normal and mutant pigs, and the clearance
      rates, interconversion rates, and production rates were determined. The sevenfold
      increase in buoyant LDL levels in the mutant pigs was due to a fivefold increase
      in buoyant LDL production. Total mutant LDL production was increased
      approximately 25%, suggesting that part of the increase in buoyant LDL production
      is at the expense of dense LDL production. Conversion of dense LDL to buoyant LDL
      made a small contribution to the buoyant LDL increase. The turnover analysis
      showed that dense LDL, in both mutant and control pigs, is primarily derived from
      a source other than buoyant LDL. To test this more directly, [3H]leucine was
      intravenously injected, and the specific activity of the LDL subspecies was
      measured over 96 hours. There was a large discrepancy in the areas under the
      specific activity-versus-time curves, indicating that buoyant LDL cannot be the
      sole precursor of dense LDL and further supporting the conclusion that buoyant
      and dense LDL are, in part, metabolically independent particles. These results
      show that genetic variation in the apo B locus can affect the synthetic rate of
      LDL and the LDL subspecies distribution.

PMID- 1998655
TI  - Identification of the base substitution responsible for the Ag(x/y) polymorphism
      of apolipoprotein B-100.
AB  - The identification of the base substitution responsible for Ag(x/y) completes the
      description of the antigen group polymorphisms associated with the apolipoprotein
      B polypeptide. Surprisingly, all five antigen group polymorphisms alter
      restriction endonuclease cleavage sites and have associated restriction fragment
      length polymorphisms, thereby providing a convenient alternative for antigen
      group phenotyping.

PMID- 1998654
TI  - Effects of the apolipoprotein E polymorphism on levels of lipids, lipoproteins,
      and apolipoproteins among Mexican-Americans in Starr County, Texas.
AB  - Genetic variability has been implicated as a significant contributor to the
      variation in levels of lipids, lipoproteins, and apolipoproteins (apos) through a
      variety of direct and indirect investigations. Among the direct investigations,
      apo E has been shown to be polymorphic and to explain a small but statistically
      significant proportion of the variability in cholesterol. The apo E polymorphism
      was typed in 964 randomly selected Mexican-Americans from Starr County, Tex., and
      its effects determined on levels of cholesterol, triglycerides, total high
      density lipoprotein (HDL) cholesterol, subfractions (HDL2 and HDL3), alpha- and
      beta-lipoprotein cholesterol, low density lipoprotein (LDL) cholesterol, and apos
      A-I, A-II, B, C-II, C-III, and E. Effects are reported for the entire sample and
      in each of three groups, namely, premenopausal females, postmenopausal women, and
      males. In the entire sample, significant effects were observed on cholesterol,
      beta-lipoprotein cholesterol, LDL, apo B, and apo E. There is evidence for
      significant physiological interaction of the apo E polymorphism effect in females
      by menopausal status. This is most evident for apo E levels, in which 5.9% of the
      variability in the entire sample is explained by the apo E polymorphism. In
      premenopausal females, however, the polymorphism accounts for 27.5% of the
      variability. In postmenopausal women and males, there is no significant effect.
      It is shown that the apo E polymorphism can be treated as a two-locus, two-allele
      system. Doing so identifies substitutions in amino acid position 158 as the
      mediators of most of the observed effects of this polymorphism.

PMID- 1998656
TI  - Evaluation of human panelists in assessing coronary atherosclerosis.
AB  - The Cholesterol Lowering Atherosclerosis Study, a randomized, angiographic
      clinical trial, has demonstrated the beneficial effect of niacin/colestipol
      therapy on coronary and femoral atherosclerosis. The primary outcome was a panel
      determined consensus score evaluating global coronary changes determined
      angiographically at 2 years. This article presents an evaluation of interreader
      agreement in independently assessing the status of native coronary arteries and
      overall coronary condition. Parameters include 1) identification of the presence
      of lesions and lesion changes; 2) estimation of lesion severity (percent
      stenosis) and amount of change in lesion severity; and 3) global assessment of
      change in coronary status. Readers independently agreed on 1) presence of lesions
      (82%) and change in lesions (51%); 2) percent stenosis +/- 10% (76%) and change
      in stenosis +/- 10% (81%); and 3) global assessment of change in coronary status
      within one step (96%). Results of these analyses may be useful in effectively
      designing angiographic trials that use a panel of human evaluators as well as
      computerized methods for angiographic interpretation.

PMID- 1998657
TI  - Platelet deposition at high shear rates is enhanced by high plasma cholesterol
      levels. In vivo study in the rabbit model.
AB  - We have studied the effects of high plasma cholesterol levels on platelet-vessel
      wall interactions under high shear rate conditions typical of the apex of
      stenotic arteries (2,600 sec-1). Hypercholesterolemia was induced by feeding
      rabbits a 0.5% cholesterol-rich diet for 60 days. Platelet deposition was studied
      by use of an annular perfusion chamber and de-endothelialized abdominal rabbit
      aortas as substrates. After ingestion of the atherogenic diet, the experimental
      group of animals developed severe hypercholesterolemia, platelets became more
      fluid as determined by steady-state fluorescence anisotropy (p less than 0.05),
      and red blood cell deformability was decreased (p less than 0.001) when compared
      with normal controls. The fatty acid composition of platelet membranes showed an
      increase in the percentage of the long-chain saturated fatty acids (palmitic,
      C16:0, and stearic, C18:0) that may account for the lower
      polyunsaturated/saturated fatty acid ratio observed in the hyperlipemic animals.
      Total platelet deposition was significantly increased (p less than 0.05) in the
      hyperlipemic group as compared with the control group at 5 minutes' perfusion
      time, becoming less evident at 20 minutes' perfusion time. Our results suggest
      that the presence of hyperlipidemia may contribute to acute thrombosis by
      enhancing platelet-vessel wall interaction.

PMID- 1998658
TI  - High density lipoprotein apolipoproteins mediate removal of sterol from
      intracellular pools but not from plasma membranes of cholesterol-loaded
      fibroblasts.
AB  - Cultured cells possess high-affinity binding sites (receptors) for high density
      lipoprotein (HDL) that appear to mediate removal of excess intracellular
      cholesterol from cells. To examine the role of intact HDL apoproteins in receptor
      mediated cholesterol removal, HDL3 apoproteins were digested with the proteolytic
      enzymes trypsin and pronase, and the residual particles were used in sterol
      efflux experiments. Protease treatment abolished the interaction of HDL3 with the
      110-kd cell membrane protein postulated to represent the HDL receptor molecule,
      indicating that this interaction is mediated by HDL apoproteins rather than
      lipids. Compared with native HDL3 protease-modified HDL3 had a markedly reduced
      ability to selectively remove sterol from intracellular pools, even though
      modified particles promoted greater cholesterol efflux from the plasma membrane
      than did native particles. These results indicate that whereas sterol efflux from
      plasma membranes is mediated by HDL lipids, removal of excess intracellular
      sterol from cells is mediated by HDL apoproteins. These findings are consistent
      with the hypothesis that receptor binding of HDL apoproteins stimulates
      translocation of excess intracellular sterol to the cell surface where it becomes
      accessible for removal by HDL or other lipid-rich acceptor particles.

PMID- 1998659
TI  - n-3 fatty acids and leukocyte chemotaxis. Effects in hyperlipidemia and dose
      response studies in healthy men.
AB  - Dietary supplementation with n-3 polyunsaturated fatty acids (n-3 PUFAs) has been
      shown to inhibit neutrophil and monocyte chemotaxis in healthy subjects and, with
      respect to neutrophils, also in various patient groups. We studied the effect of
      dietary supplementation with n-3 PUFAs on monocyte and neutrophil chemotaxis in
      patients with hyperlipidemia. Chemotaxis was investigated with the under-agarose
      assay, using autologous serum and N-formyl-methionyl-leucyl-phenylalanine as
      chemoattractants. The patients were examined before and after 6 weeks of
      supplementation with 6 g n-3 PUFAs daily. Monocyte chemotaxis was reduced after n
      3 PUFA supplementation in type IIa patients but was unaffected in patients with
      type IV hyperlipidemia. Furthermore, monocyte chemotaxis was increased in
      untreated type IIa patients compared with normocholesterolemic controls. We also
      studied the dose-response effects of n-3 PUFAs on monocyte and neutrophil
      chemotaxis in healthy men given 1.3, 4, and 9 g n-3 PUFAs daily for 6-week
      periods. Monocyte and neutrophil chemotaxis was reduced after n-3 PUFA
      supplements in a dose-dependent fashion, with the majority of the effect observed
      after the low dose. These results lend support to the notion of an
      antiatherosclerotic effect of n-3 PUFAs and may provide an explanation for the
      hitherto-unexplained effect of low doses of n-3 PUFAs in coronary heart disease.

PMID- 1998660
TI  - Platelet adhesion to exposed endothelial cell extracellular matrixes is
      influenced by the method of preparation.
AB  - The relative thrombogenicity of extracellular matrixes (ECMs) produced by
      cultured human umbilical endothelial cells (ECs) was studied under flow
      conditions. ECMs were prepared using a number of physical and chemical methods,
      and their reactivity toward platelets was morphometrically evaluated. von
      Willebrand factor (vWF), fibronectin (FN), and 13-hydroxy-9-cis,11-trans
      octadecadienoic acid (13-HODE) were also determined. We found that platelet
      adhesion to ECMs differed significantly, both quantitatively and qualitatively,
      with the method of ECM preparation. Mechanically prepared ECM exposed a less
      thrombogenic surface compared with ECM prepared by chemical methods (platelet
      covered surface of 20% and 50%, respectively). Evaluation of the ECM components
      vWF, FN, and 13-HODE showed significant changes, both in their concentrations and
      distribution patterns, depending on the method of ECM preparation. The decrease
      measured in the levels of ECM-associated vWF (from 108 to 9.2 ng/10(4) cells) and
      the minor changes observed in the distribution pattern of subendothelial FN did
      not appear to be sufficient to explain the altered platelet adhesion observed in
      our model. This suggests that the amount of 13-HODE probably associated to the
      remaining ECs present in the mechanically exposed ECM could be one factor that
      specifically contributed to the nonthrombogenic state of these preparations. We
      conclude that the degree of ECM reactivity toward platelets is dependent on the
      method of ECM preparation and that this is related to the removal of specific
      EC/ECM components that modulate their thromboresistant/thrombogenic properties.
      This fact should be taken into account when ECMs produced by cultured ECs are
      used in platelet adhesion studies.

PMID- 1998661
TI  - Progression and regression of carotid atherosclerosis in clinical trials.

PMID- 1998662
TI  - Lipoproteins and the pathobiology of the arterial intima. Ninth Paavo Nurmi
      Symposium.

PMID- 1998663
TI  - Toward a simplification of the protein folding problem: a stabilizing polyalanine
      alpha-helix engineered in T4 lysozyme.
AB  - In an attempt to simplify the protein folding problem, and also to further
      investigate the role of alanine as a helix-stabilizing residue, a series of
      alanines was introduced within the alpha-helix that includes residues 126-134 of
      T4 lysozyme. In wild-type lysozyme this alpha-helix contains alanine residues at
      positions 129, 130, and 134. Mutant lysozymes with alanines substituted at
      positions 128, 131, 132, and 133, either as single substitutions or in selected
      combinations, were constructed by oligonucleotide-directed mutagenesis. With the
      exception of the replacement of Leu 133, which is buried within the hydrophobic
      core of the protein, all the variants were more stable than wild-type lysozyme.
      The variant with alanines substituted at positions 128, 131, and 132
      (E128A/V131A/N132A), which incorporates the sequence Ala 128-Ala 129-Ala 130-Ala
      131-Ala 132-Leu 133-Ala 134, has a melting temperature 3.3 degrees C above that
      of wild-type lysozyme. Determination of the crystal structure of this mutant
      lysozyme shows that the replacement of Glu 128, Val 131, and Asn 132 with alanine
      causes alpha-helix 126-134 to rotate 3.4 degrees about an axis parallel to its
      own axis. This rotation seems to be triggered primarily by the loss of a hydrogen
      bond between Asn 132 and Ser 117 and is associated with the repacking of several
      side chains at the interface between alpha-helix 126-134 and the adjacent alpha
      helix 115-122.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1998664
TI  - Identification of vancomycin resistance protein VanA as a D-alanine:D-alanine
      ligase of altered substrate specificity.
AB  - High-level glycopeptide resistance in Enterococcus faecium BM4147 is mediated by
      a 38-kDa protein VanA, whose amino acid sequence is related to Gram-negative D
      alanine:D-alanine (D-Ala-D-Ala) ligases [Dutka-Malen, S., Molinas, C., Arthur,
      M., & Courvalin, P. (1990) Mol. Gen. Genet. 224, 364-372]. We report purification
      of VanA and demonstrate that it has D-Ala-D-Ala ligase activity but has
      substantially modified substrate specificity, compared with Gram-negative D-Ala-D
      Ala ligases. VanA preferentially condenses D-Ala with D-Met or D-Phe, raising the
      possibility that its cellular role is to synthesize a modified cell-wall
      component, which is subsequently not recognized by vancomycin.

PMID- 1998665
TI  - Alternative secondary structures in the 5' exon affect both forward and reverse
      self-splicing of the Tetrahymena intervening sequence RNA.
AB  - The natural splice junction of the Tetrahymena large ribosomal RNA is flanked by
      hairpins that are phylogenetically conserved. The stem immediately preceding the
      splice junction involves nucleotides that also base pair with the internal guide
      sequence of the intervening sequence during splicing. Thus, precursors which
      contain wild-type exons can form two alternative helices. We have constructed a
      series of RNAs where the stem-loop in the 5' exon is more or less stable than in
      the wild-type precursor, and tested them in both forward and reverse self
      splicing reactions. The presence of a stable hairpin in ligated exon substrates
      interferes with the ability of the intervening sequence to integrate at the
      splice junction. Similarly, the presence of the wild-type hairpin in the 5' exon
      reduces the rate of splicing 20-fold in short precursors. The data are consistent
      with a competition between unproductive formation of a hairpin in the 5' exon and
      productive pairing of the 5' exon with the internal guide sequence. The reduction
      of splicing by a hairpin that is a normal feature of rRNA structure is
      surprising; we propose that this attenuation is relieved in the natural splicing
      environment.

PMID- 1998666
TI  - Location of the disulfide bonds in human plasma prekallikrein: the presence of
      four novel apple domains in the amino-terminal portion of the molecule.
AB  - The location of 16 of the 18 disulfide bonds in human plasma prekallikrein was
      determined by amino acid sequence analysis of cystinyl peptides produced by
      chemical and enzymatic digestions. A unique structure, named the apple domain,
      was established for each of the four tandem repeats in the amino-terminal portion
      of the molecule. The apple domains (90 or 91 amino acids) contain 3 highly
      conserved disulfide bonds linking the first and sixth, second and fifth, and
      third and fourth half-cystine residues present in each repeat. The fourth tandem
      repeat contains an extra disulfide bond that forms a second small loop within the
      apple domain. The carboxyl-terminal portion of plasma prekallikrein containing
      the catalytic region of the molecule was found to have disulfide bonds located in
      positions similar to those of other serine proteases.

PMID- 1998667
TI  - Location of the disulfide bonds in human coagulation factor XI: the presence of
      tandem apple domains.
AB  - Factor XI is a plasma glycoprotein that participates in the blood coagulation
      cascade. Of the 19 disulfide bonds present in each of the subunits of the human
      protein, 16 were determined by amino acid sequence analysis of peptide fragments
      produced by chemical and enzymatic digestion. Four apple domains of 90 or 91
      amino acids were identified in the tandem repeats present in the amino-terminal
      portion of each subunit of factor XI. The disulfide bonds in the carboxyl
      terminal portion of the molecule were similar to those in the catalytic region of
      other serine proteases. The two identical subunits of factor XI were connected by
      a single disulfide bond at Cys321 linking each of the fourth apple domains while
      each of the Cys residues at position 11 in the first apple domains forms a
      disulfide bond with another Cys residue.

PMID- 1998668
TI  - Kinetic study on the irreversible thermal denaturation of yeast phosphoglycerate
      kinase.
AB  - Differential scanning calorimetry transitions for the irreversible thermal
      denaturation of yeast phosphoglycerate kinase at pH 7.0 are strongly scanning
      rate dependent, suggesting that the denaturation is, at least in part, under
      kinetic control. To test this possibility, we have carried out a kinetic study on
      the thermal inactivation of the enzyme. The inactivation kinetics are
      comparatively fast within the temperature range of the calorimetric transitions
      and can be described phenomenologically by the equation dC/dt = -alpha C2/(beta +
      C), where C is the concentration of active enzyme at a given time, t, and alpha
      and beta are rate coefficients that depend on temperature. This equation,
      together with the values of alpha and beta (within the temperature range 50-59
      degrees C) have allowed us to calculate the fraction of irreversibly denatured
      protein versus temperature profiles corresponding to the calorimetric
      experiments. We have found that (a) irreversible denaturation takes place during
      the time the protein spends in the transition region and (b) there is an
      excellent correlation between the temperatures of the maximum of the calorimetric
      transitions (Tm) and the temperatures (Th) at which half of the protein is
      irreversibly denatured. These results show that the differential scanning
      calorimetry transitions for the denaturation of phosphoglycerate kinase are
      highly distorted by the rate-limited irreversible process. Finally, some comments
      are made as to the use of equilibrium thermodynamics in the analysis of
      irreversible protein denaturation.

PMID- 1998669
TI  - Effect of Zn2+ on the thermal denaturation of carboxypeptidase B.
AB  - A differential scanning calorimetry study on the thermal denaturation of porcine
      pancreas carboxypeptidase B (in 20 mM pyrophosphate buffer, pH 9.0) has been
      carried out. The calorimetric transitions have been found to be calorimetrically
      irreversible and to depend on the Zn2+ concentration in the buffer. The effect of
      the Zn2+ concentration on the temperatures corresponding to maximum heat capacity
      appears to conform the dictates of the van't Hoff equation. In spite of this,
      analysis of the scanning rate effect on the transitions, together with studies on
      the thermal inactivation kinetics, show that the heat absorption is entirely
      determined by the rate of formation of the final (irreversibly denatured) state
      of the protein; therefore, analysis of the calorimetric transitions according to
      equilibrium thermodynamics models is not permissible. The effect of Zn2+ on the
      calorimetric transitions can be explained on the basis of a simple kinetic model
      that does not assume chemical equilibrium to be established between the
      significantly populated states of the protein.

PMID- 1998670
TI  - Neutral oligosaccharide structures linked to asparagines of porcine zona
      pellucida glycoproteins.
AB  - N-Linked sugar chains were liberated by hydrazinolysis from porcine zona
      pellucida glycoproteins obtained from ovarian follicular oocytes. Neutral sugar
      chains were separated from acidic ones by paper electrophoresis and fractionated
      with a serial lectin column chromatography and Bio-Gel P-4 column chromatography.
      Their structural analysis by sequential glycosidase digestion in combination with
      methylation analysis revealed that the neutral sugar chains are of bi-, tri-, and
      tetraantennary complex type with a fucosylated trimannosyl core. Twenty-six
      percent of the sugar chains contain N-acetyllactosamine repeating structures in
      their outer chain moieties. Only linear N-acetyllactosamine repeats, the maximum
      size of which is hexasaccharide, are detected. A characteristic feature is that
      39% of the sugar chains contain N-acetylglucosamine residues at their nonreducing
      termini in spite of the absence of bisected sugar chains. This study provided,
      for the first time, the substantial information about the sugar chain structures
      of mammalian zona pellucida glycoproteins.

PMID- 1998671
TI  - Action of insulin in rat adipocytes and membrane properties.
AB  - Several small peptides inhibit insulin-promoted glucose uptake in rat adipocytes.
      At 10 microM peptide concentration, the extent of their inhibition of the insulin
      effect is related to the ability of these peptides to raise the bilayer- to
      hexagonal-phase transition temperature in model membranes. Hexane and DL-threo
      dihydrosphingosine lower this phase transition temperature in model membranes,
      and they promote glucose uptake in adipocytes. There is thus an empirical
      relationship between the action of membrane additives on glucose uptake in
      adipocytes and their effect on the hexagonal-phase-forming tendency in model
      membranes. The most potent of the bilayer-stabilizing peptides tested in this
      work is carbobenzoxy-D-Phe-L-Phe-Gly. This peptide also inhibits insulin
      stimulated protein synthesis in adipocytes. In contrast, DL-threo
      dihydrosphingosine stimulates protein synthesis. The uptake of [125I]iodoinsulin
      by adipocytes is inhibited by carbobenzoxy-D-Phe-L-Phe-Gly. The mechanism of
      action of the bilayer-stabilizing peptides includes inhibition of insulin
      dependent protein phosphorylation in adipocytes. The peptides are not specific
      inhibitors of a single function but are suggested to cause their effects by
      altering the physical properties of the membrane in a nonspecific manner. These
      results demonstrate that insulin-dependent functions of rat adipocytes can be
      modified by membrane additives in a manner predictable from the properties of
      these additives in model membranes.

PMID- 1998672
TI  - Mean field stochastic boundary molecular dynamics simulation of a phospholipid in
      a membrane.
AB  - Computer simulations of phospholipid membranes have been carried out by using a
      combined approach of molecular and stochastic dynamics and a mean field based on
      the Marcelja model. First, the single-chain mean field simulations of Pastor et
      al. [(1988) J. Chem. Phys. 89, 1112-1127] were extended to a complete
      dipalmitoylphosphatidylcholine molecule; a 102-ns Langevin dynamics simulation is
      presented and compared with experiment. Subsequently, a hexagonally packed seven
      lipid array was simulated with Langevin dynamics and a mean field at the boundary
      and with molecular dynamics (and no mean field) in the center. This hybrid
      method, mean field stochastic boundary molecular dynamics, reduces bias
      introduced by the mean field and eliminates the need for periodic boundary
      conditions. As a result, simulations extending to tens of nanoseconds may be
      carried out by using a relatively small number of molecules to model the membrane
      environment. Preliminary results of a 20-ns simulation are reported here. A wide
      range of motions, including overall reorientation with a nanosecond decay time,
      is observed in both simulations, and good agreement with NMR, IR, and neutron
      diffraction data is found.

PMID- 1998673
TI  - Fourier-transform infrared spectroscopy study of dioleoylphosphatidylcholine and
      monooleoylglycerol in lamellar and cubic liquid crystals.
AB  - The liquid-crystalline phases of the systems monooleoylglycerol (MO)/water,
      dioleoylphosphatidylcholine (DOPC)/water, and MO/DOPC/water have been studied by
      Fourier-transform infrared (FTIR) spectroscopy. In the latter ternary system, the
      sn-3 OH group of MO competes with water to interact with the polar head group of
      DOPC, and an intramolecular hydrogen bonding of MO is broken up. The hydration of
      the ester carbonyl groups in the lamellar phases of both the MO/water and
      DOPC/water systems increases with increasing water content. Similarly, the
      addition of small amounts either of MO to a DOPC/water system or of DOPC to an
      MO/water system also results in an increase in the hydration of the ester
      carbonyl groups. This leads to an unfavorable hydrocarbon-water contact which is
      counteracted by the formation of a cubic phase, except for the DOPC/water system,
      where the lamellar phase is stable also at the highest water concentrations. The
      phase behavior of the different systems can be described in terms of lipid
      monolayer curvature and molecular packing in the lipid aggregates. Finally, it is
      shown by the water association band in the FTIR spectrum that the water hydrogen
      bonding is considerably different in the liquid-crystalline phases than in bulk
      water.

PMID- 1998674
TI  - Diacetylenic lipid microstructures: structural characterization by X-ray
      diffraction and comparison with the saturated phosphatidylcholine analogue.
AB  - Thermotropic and lyotropic mesomorphism in the polymerizable lecithin 1,2
      ditricosa-10,12-diynoyl-sn-glycero-3-phosphocholine and its saturated analogue,
      1,2-ditricosanoyl-sn-glycero-3-phosphocholine, has been investigated by wide- and
      low-angle X-ray diffraction of both powder and oriented samples and by
      differential scanning calorimetry. Previous studies have shown that the hydrated
      diacetylenic lipid forms novel microstructures (tubules and stacked bilayer
      sheets) in its low-temperature phase. The diffraction results indicate that at
      low temperatures fully hydrated tubules and sheets have an identical lamellar
      repeat size (d001 = 66.4 A) and crystalline-like packing of the acyl chains.
      Chain packing in the lamellar crystalline phase is hydration independent. A model
      for the polymerizable lecithin with (1) fully extended all-trans methylene
      segments, (2) a long-axis tilt of 32 degrees, and (3) minimal chain
      interdigitation seems most reasonable on energetic grounds, is consistent with
      the diffraction data (to 3.93-A resolution), and is likely to support facile
      polymerization. Above the chain "melting" transition the lamellar repeat of the
      polymerizable lipid increases to 74 A. The conformational similarity between
      tubules, sheets, and the dry powder is corroborated by calorimetry, which reveals
      a cooling exotherm at the same temperature where tubules form upon cooling
      hydrated sheets. The data suggest that although a high degree of conformational
      order is a pertinent feature of tubules, this character alone is not sufficient
      to account for tubule formation. The conformation of the corresponding saturated
      phosphatidylcholine appears to be similar to that of other saturated
      phosphatidylcholines in the lamellar gel phase. Furthermore, above the main
      transition temperature, the dry, saturated lipid shows evidence of a P delta
      phase (112 degrees C), whereas the diacetylenic lipid appears to exhibit a
      centered rectangular phase, R alpha (55 degrees C).

PMID- 1998675
TI  - On the use of deuterium nuclear magnetic resonance as a probe of chain packing in
      lipid bilayers.
AB  - The packing of hydrocarbon chains in the bilayers of lamellar (L alpha) phases of
      soap/water and phospholipid/water mixtures has been studied by deuterium NMR
      spectroscopy and X-ray diffraction. A universal correlation is shown to exist
      between the average C-D bond order parameter SCD of hydrocarbon chains and the
      average area per chain ach, irrespective of the chemical structure of the
      surfactant (hydrophilic group, number of chains per molecule, and chain length),
      composition, and temperature. The practical utility of the correlation is
      illustrated by its application to the characterization of the distribution of
      various hydrophobic and amphiphilic solutes in bilayers. The distribution of
      hydrocarbons within a bilayer is shown to depend upon their molecular structure
      in a manner which highlights the nature of the molecular interactions involved.
      For example, benzene is shown to be fairly uniformly distributed across the
      bilayer with an increasing tendency to distribute into the center at high
      concentrations. In contrast, the more complex hydrocarbon tetradecane
      preferentially distributes into the center of the bilayer at low concentrations,
      while at higher concentrations it intercalates between the surfactant chains.
      Alcohols such as benzyl alcohol, octanol, and decanol all interact similarly with
      the bilayer in so far as they are pinned to the polar/apolar interface,
      presumably by involvement of the hydroxyl group in a hydrogen bond. But the
      response of the surfactant chains to the void volume created in the center of the
      bilayer is dependent upon the distance of penetration of the alcohol into the
      bilayer. For benzyl alcohol, the shortest molecule, this void volume is taken up
      by the disordering of the chains, while for decanol, the longest molecule, it is
      absorbed by interdigitation of the chains of apposing monolayers. For octanol,
      the chain interdigitation mechanism is dominant at low concentrations, but there
      is a transition to chain disordering at high concentrations. Finally, it is shown
      that the correlation provides a useful test for statistical mechanical models of
      chain ordering in lipid bilayers.

PMID- 1998676
TI  - 1H NMR study of the solution molecular and electronic structure of Escherichia
      coli ferricytochrome b562: evidence for S = 1/2 in equilibrium S = 5/2 spin
      equilibrium for intact His/Met ligation.
AB  - The solution 500-MHz 1H NMR spectral parameters for ferricytochrome b562, a
      soluble 12-kDa electron carrier from Escherichia coli with axial His/Met
      coordination, are shown to be strongly influenced by protein concentration and
      ionic strength at low pH and 25 degrees C in a manner consistent with significant
      aggregation at low ionic strength. At high ionic strength a well-resolved 1H NMR
      spectrum reveals over 40 hyperfine-shifted resonances which arise from two
      isomeric species in the ratio 2:1. 2D COSY and NOESY maps at 25 degrees C for the
      hyperfine-shifted resonances allow the assignment of a number of axial His
      resonances and all heme peripheral substituent peaks. The resulting asymmetric
      heme contact shift patterns, together with the halving of the number of lines
      when reconstituting with 2-fold symmetric hemin, demonstrate the molecular basis
      of the solution heterogeneity to be heme orientational disorder. The strongly
      upfield-shifted axial Met-7 resonances, characteristic of low-spin
      ferricytochromes c with His/Met ligation, appear upfield only at very low
      temperatures. At elevated temperatures, all resonances, in particular those of
      the axial Met, move strongly downfield. Detailed analysis of the deviation from
      Curie behavior for different functional groups demonstrates the presence of a low
      spin in equilibrium high spin equilibrium with an intact His-Fe-Met coordination.
      The weaker axial field in ferricytochrome b562, relative to the purely low-spin
      ferricytochromes c, is attributed to a perturbed iron-Met bond. The contact
      shifts for a coordinated Met in the high-spin state are estimated. A link between
      equatorial hemin and axial ligand interactions is indicated by a differential
      population of the high-spin form for the two hemin orientations.

PMID- 1998677
TI  - Structural study of porcine pancreatic elastase complexed with 7-amino-3-(2
      bromoethoxy)-4-chloroisocoumarin as a nonreactivatable doubly covalent enzyme
      inhibitor complex.
AB  - The complex of porcine pancreatic elastase (PPE) with 7-amino-3-(2-bromoethoxy)-4
      chloroisocoumarin, a potent mechanism-based inhibitor, was crystallized and the
      crystal structure determined at 1.9-A resolution with a final R factor of 17.1%.
      The unbiased difference Fourier electron density map showed continuous density
      from O gamma of Ser 195 to the benzoyl carbonyl carbon atom and from N epsilon 2
      of His 57 to the carbon atom at the 4-position of the isocoumarin ring in the
      inhibitor. This suggested unambiguously that the inhibitor was doubly covalently
      bound to the enzyme. It represents the first structural evidence for irreversible
      binding of an isocoumarin inhibitor to PPE through both Ser 195 and His 57 in the
      active site. The PPE-inhibitor complex is only partially activated in solution by
      hydroxylamine and confirms the existence of the doubly covalently bound complex
      along with the acyl enzyme. The benzoyl carbonyl oxygen atom of the inhibitor is
      not situated in the oxyanion hole formed by the amide (greater than NH) groups of
      Gly 193 and Ser 195. The complex is stabilized by the hydrogen-bonding
      interactions in the active site (from the N epsilon 2 of Gln 192 to the bromine
      atom in the inhibitor and the amino group at the 7-position of the isocoumarin
      ring to the carbonyl oxygen of Thr 41) and by van der Waals interactions. The
      inhibition rates of several 7-substituted 4-chloro-3-(bromoalkoxy)isocoumarins
      toward PPE were measured.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1998678
TI  - Evidence for two interconverting protein isomers in the methotrexate complex of
      dihydrofolate reductase from Escherichia coli.
AB  - Two-dimensional 1H NMR methods and a knowledge of the X-ray crystal structure
      have been used to make resonance assignments for the amino acid side chains of
      dihydrofolate reductase from Escherichia coli complexed with methotrexate. The H7
      proton on the pteridine ring of methotrexate was found to have NOEs to the methyl
      protons of Leu-28 which were assigned by using the L28F mutant. These NOEs
      indicated that the orientation of the methotrexate pteridine ring is similar in
      both solution and crystal structures. During the initial assignment process, it
      became evident that many of the resonances in this complex, unlike those of the
      folate complex, are severely broadened or doubled. The observation of two
      distinct sets of resonances in a ratio of approximately 2:1 was attributed to the
      presence of two protein isomers. At 303 K, NOESY spectra with mixing times of 100
      ms did not show interconversion between these isomers. However, exchange cross
      peaks were observed in a 700-ms NOESY spectrum at 323 K which demonstrated that
      these isomers are interconverting slowly on the NMR time scale. Many of the side
      chains with clearly doubled resonances were located in the beta-sheet and the
      active site. Preliminary studies on the apoprotein also revealed doubled
      resonances in the absence of the inhibitor, indicating the existence of the
      protein isomers prior to methotrexate binding. In contrast to the methotrexate
      complex, the binary complex with folate and the ternary MTX-NADPH-DHFR complex
      presented a single enzyme form. These results are proposed to reflect the ability
      of folate and NADPH to bind predominantly to one protein isomer.

PMID- 1998679
TI  - Kinetics of electron transfer from thioredoxin reductase to thioredoxin.
AB  - The reduction of Escherichia coli thioredoxin by thioredoxin reductase was
      studied by stopped-flow spectrophotometry. The reaction showed no dependence on
      thioredoxin concentration, indicating that complex formation was rapid and
      occurred during the dead time of the instrument. The kobs for the reaction of
      approximately 20 s-1 probably reflects the rate of electron transfer from
      thioredoxin reductase to thioredoxin and agrees with the kcat observed by steady
      state kinetics. The reaction rate was unaffected by increasing the ionic
      strength, suggesting a lack of electrostatic stabilization in the interaction of
      the two proteins. A mutant thioredoxin in which a positively charged lysine in
      the active-site region was changed to a glutamic acid residue resulted in an
      electrostatic destabilization. Thioredoxin K36E was still a substrate for the
      reductase, but binding was impaired so that the rate could be measured by stopped
      flow techniques as reflected by a dependence on protein concentration. Raising
      the ionic strength in this reaction served to shield the negative charge and
      increased the rate of binding to the reductase.

PMID- 1998680
TI  - Human and murine cytotoxic T lymphocyte serine proteases: subsite mapping with
      peptide thioester substrates and inhibition of enzyme activity and cytolysis by
      isocoumarins.
AB  - The active site structures of human Q31 granzyme A, murine granzymes (A, B, C, D,
      E, and F), and human granzymes (A, B, and 3) isolated from cytotoxic T
      lymphocytes (CTL) were studied with peptide thioester substrates, peptide
      chloromethyl ketone, and isocoumarin inhibitors. Human Q31, murine, and human
      granzyme A hydrolyzed Arg- or Lys-containing thioesters very efficiently with
      kcat/KM of 10(4)-10(5) M-1 s-1. Murine granzyme B was found to have Asp-ase
      activity and hydrolyzed Boc-Ala-Ala-Asp-SBzl with a kcat/KM value of 2.3 X 10(5)
      M-1 s-1. The rate was accelerated 1.4-fold when the 0.05 M NaCl in the assay was
      replaced with CaCl2. The preparation of granzyme B also had significant activity
      toward Boc-Ala-Ala-AA-SBzl substrates, where AA was Asn, Met, or Ser [kcat/KM =
      (4-5) X 10(4) M-1 s-1]. Murine granzymes C, D, and E did not hydrolyze any
      thioester substrate but contained minor contaminating activity toward Arg- or Lys
      containing thioesters. Murine granzyme F had small activity toward Suc-Phe-Leu
      Phe-SBzl, along with some contaminating trypsin-like activity. Human Q31 granzyme
      A, murine, and human granzyme A were inhibited quite efficiently by mechanism
      based isocoumarin inhibitors substituted with basic groups (guanidino or
      isothiureidopropoxy). Although the general serine protease inhibitor 3,4
      dichloroisocoumarin (DCI) inactivated these tryptases poorly, it was the best
      isocoumarin inhibitor for murine granzyme B (kobs/[I] = 3700-4200 M-1 s-1).
      Murine and human granzyme B were also inhibited by Boc-Ala-Ala-Asp-CH2Cl;
      however, the inhibition was less potent than that with DCI. DCI, 3-(3-amino
      propoxy)-4-chloroisocoumarin, 4-chloro-3-(3-isothiureidopropoxy)isocoumarin, and
      7-amino-4-chloro-3-(3-isothiureidopropoxy)isocoumarin inhibited Q31 cytotoxic T
      lymphocyte mediated lysis of human JY lymphoblasts (ED50 = 0.5-5.0 microM).

PMID- 1998681
TI  - Crystal structure of unliganded Escherichia coli dihydrofolate reductase. Ligand
      induced conformational changes and cooperativity in binding.
AB  - The crystal structure of unliganded dihydrofolate reductase (DHFR) from
      Escherichia coli has been solved and refined to an R factor of 19% at 2.3-A
      resolution in a crystal form that is nonisomorphous with each of the previously
      reported E. coli DHFR crystal structures [Bolin, J. T., Filman, D. J., Matthews,
      D. A., Hamlin, B. C., & Kraut, J. (1982) J. Biol. Chem. 257, 13650-13662;
      Bystroff, C., Oatley, S. J., & Kraut, J. (1990) Biochemistry 29, 3263-3277].
      Significant conformational changes occur between the apoenzyme and each of the
      complexes: the NADP+ holoenzyme, the folate-NADP+ ternary complex, and the
      methotrexate (MTX) binary complex. The changes are small, with the largest about
      3 A and most of them less than 1 A. For simplicity a two-domain description is
      adopted in which one domain contains the NADP+ 2'-phosphate binding site and the
      binding sites for the rest of the coenzyme and for the substrate lie between the
      two domains. Binding of either NADP+ or MTX induces a closing of the PABG-binding
      cleft and realignment of alpha-helices C and F which bind the pyrophosphate of
      the coenzyme. Formation of the ternary complex from the holoenzyme does not
      involve further relative domain shifts but does involve a shift of alpha-helix B
      and a floppy loop (the Met-20 loop) that precedes alpha B. These observations
      suggest a mechanism for cooperativity in binding between substrate and coenzyme
      wherein the greatest degree of cooperativity is expressed in the transition-state
      complex. We explore the idea that the MTX binary complex in some ways resembles
      the transition-state complex.

PMID- 1998682
TI  - Mechanism of inactivation and identification of sites of modification of
      ornithine aminotransferase by 4-aminohex-5-ynoate.
AB  - The inactivation of ornithine aminotransferase by an enzyme-activated
      irreversible inhibitor 4-aminohex-5-ynoate was accompanied by stoichiometric
      binding of the radiolabeled compound. Distribution of radiolabel among separated
      tryptic peptides indicated that more than one amino acid residue had reacted. Lys
      292 and Cys-388 were positively identified. Reduction with borohydride was
      necessary to stabilize the adduct formed with Lys-292, and the relevant peptide
      prepared after this treatment contained equimolar amounts of inhibitor and
      coenzyme. The coenzyme chromophore in this peptide showed strong negative
      circular dichroism. A mechanism consistent with these observations is proposed.

PMID- 1998683
TI  - Interaction of human placental ribonuclease with placental ribonuclease
      inhibitor.
AB  - The interactions of human placental ribonuclease inhibitor (PRI) with bovine
      pancreatic ribonuclease (RNase) A and human angiogenin, a plasma protein that
      induces blood vessel formation, have been characterized in detail in earlier
      studies. However, studies on the interaction of PRI with the RNase(s) indigenous
      to placenta have not been performed previously, nor have any placental RNases
      been identified. In the present work, the major human placental RNase (PR) was
      purified to homogeneity by a five-step procedure and was obtained in a yield of
      110 micrograms/kg of tissue. The placental content of angiogenin was also
      examined and was found to be at least 10-fold lower than that of PR. On the basis
      of its amino acid composition, amino-terminal sequence, and catalytic properties,
      PR appears to be identical with an RNase previously isolated from eosinophils
      (eosinophil-derived neurotoxin), liver, and urine. The apparent second-order rate
      constant of association for the PR.PRI complex, measured by examining the
      competition between PR and angiogenin for PRI, is 1.9 X 10(8) M-1 s-1. The rate
      constant for dissociation of the complex, determined by HPLC measurement of the
      rate of release of PR from its complex with PRI in the presence of a scavenger
      for free PRI, is 1.8 X 10(-7) s-1. Thus the Ki value for the PR.PRI complex is 9
      X 10(-16) M, similar to that obtained with angiogenin, and 40-fold lower than
      that measured with RNase A. Complex formation causes a small red shift in the
      protein fluorescence emission spectrum, with no significant change in overall
      intensity. The fluorescence quantum yield of PR and the Stern-Volmer constant for
      fluorescence quenching by acrylamide are both high, possibly due to the presence
      of an unusual posttranslationally modified tryptophan residue at position 7 in
      the primary sequence.

PMID- 1998684
TI  - Peptidic phosphonylating agents as irreversible inhibitors of serine proteases
      and models of the tetrahedral intermediates.
AB  - Peptide analogues incorporating an electrophilic phosphorus moiety (2-6) have
      been synthesized and studied as inhibitors of a variety of serine proteases.
      Inhibition is irreversible and, for alpha-lytic protease (ALP), shown to result
      from covalent binding to the active site serine hydroxyl [Bone, R., Sampson, N.
      S., Bartlett, P.A., & Agard, D. A. (1991) Biochemistry (following paper in this
      issue)]. For reaction of human leukocyte elastase (HLE) with the thiophenyl
      esters 6s-V (Boc-AAPV psi [P = O(SPh)O]AA-OMe), 4s-V (BocAAPV psi [P = O(SPh)O]
      Me), and 3s-V (Boc-V psi [P = O(SPh)O]AA-OMe), evidence is presented to suggest
      that the S4-S1 subsites, but not the S1' and S2' positions, are occupied by the
      inhibitors during the inactivation process. The selectivity that is observed
      between the proteases and the hexapeptide phosphonates 6o-V (Boc-AAPV psi [P =
      O(OPh)O]AA-OMe) and 6o-F (Boc-AAPF psi [P = O(OPh)O]AA-OMe) parallels that
      between these enzymes and their substrates: ALP and HLE are selectively
      inactivated by the ValP-containing analogue 6o-V, while subtilisin (SUB) shows a
      preference for the PheP derivative 6o-F. A detailed kinetic analysis of the
      enzyme-inhibitor interactions was complicated by the susceptibility of the
      inhibitors to enzymatic degradation. The configuration at phosphorus was found
      not to have a significant influence on the rate at which the inhibitors react
      with the peptidases. Moreover, in the case of inactivation of ALP by the
      hexapeptide 6o-V, the same covalent adduct is formed from both stereoisomers
      (Bone et al., 1991), indicating that one of these diastereomers undergoes
      substitution with retention of configuration.

PMID- 1998685
TI  - Crystal structures of alpha-lytic protease complexes with irreversibly bound
      phosphonate esters.
AB  - The structures of the complexes with alpha-lytic protease of both phosphorus
      stereoisomers of N-[(2S)-2-[[[(1R)-1-[N-[(tert-butyloxycarbonyl)-L-alanyl-L
      alanyl- L-prolyl]amino]-2-methylpropyl]-phenoxyphosphinyl]oxy]propanoyl]- L
      alanine methyl ester, an analogue of the peptide Boc-Ala-Ala-Pro-Val-Ala-Ala
      where Val is replaced with an analogous phosphonate phenyl ester and the
      subsequent Ala is replaced with lactate, have been determined to high resolution
      (1.9 A) by X-ray crystallography. Both stereoisomers inactivate the enzyme but
      differ by a factor of 2 in the second-order rate constant for inactivation
      [Sampson, N. S., & Bartlett, P. A. (1991) Biochemistry (preceding paper in this
      issue)]. One isomer (B) forms a tetrahedral adduct in which the phosphonate
      phenyl ester is displaced by the active site serine (S195) and interacts with the
      enzyme across seven substrate recognition sites that span both sides of the
      scissile bond. Seven hydrogen bonds are formed with the enzyme, and 510 A2 of
      hydrophobic surface area is buried when the inhibitor interacts with the enzyme.
      Although two hydrogen bonds are gained by incorporation of two residues on the C
      terminal side of the scissile bond into the inhibitor, there is very little
      adjustment in the structure of the enzyme in this region. Surprisingly, the
      active site histidine (H57) does not interact with the phosphonate, apparently
      because the phosphonate lacks negative charge in or near the oxyanion hole, and
      instead, the side chain rotates out of the active site cleft and hydrogen bonds
      with solvent. The other isomer (A) forms a mixture of two different tetrahedral
      adducts in the active site, both covalently bonded to Ser 195. One adduct, at
      approximately 58% occupancy, is exactly the same in structure as the complex
      formed with isomer B, and the other adduct, at 42% occupancy, has lost the two
      residues C-terminal to the scissile bond by hydrolysis. In the lower occupancy
      structure, His 57 does not rotate out of the active site and forms a hydrogen
      bond with the phosphonate oxygen instead. The structures of both complexes were
      insensitive to pH. As very little change in structure accompanies the histidine
      rotation, the complex with isomer B provides an excellent mimic for the structure
      of the transition state (or high-energy reaction intermediate) that spans both
      sides of the scissile bond.

PMID- 1998686
TI  - Deduced amino acid sequence of Escherichia coli adenosine deaminase reveals
      evolutionarily conserved amino acid residues: implications for catalytic
      function.
AB  - The goal of the research reported here is to identify evolutionarily conserved
      amino acid residues associated with enzymatic deamination of adenosine. To do
      this, we isolated molecular clones of the Escherichia coli adenosine deaminase
      gene by functional complementation of adenosine deaminase deficient bacteria and
      deduced the amino acid sequence of the enzyme from the nucleotide sequence of the
      gene. Nucleotide sequence analysis revealed the presence of a 996-nucleotide open
      reading frame encoding a protein of 332 amino acids having a molecular weight of
      36,345. The deduced amino acid sequence of the E. coli enzyme has approximately
      33% identity with those of the mammalian adenosine deaminases. With conservative
      amino acid substitutions the overall sequence homology approaches 50%, suggesting
      that the structures and functions of the mammalian and bacterial enzymes are
      similar. Additional amino acid sequence analysis revealed specific residues that
      are conserved among all three adenosine deaminases and four AMP deaminases for
      which sequence information is currently available. In view of previously
      published enzymological data and the conserved amino acid residues identified in
      this study, we propose a model to account for the enzyme-catalyzed hydrolytic
      deamination of adenosine. Potential catalytic roles are assigned to the conserved
      His 214, Cys 262, Asp 295, and Asp 296 residues of mammalian adenosine deaminases
      and the corresponding conserved amino acid residues in bacterial adenosine
      deaminase and the eukaryotic AMP deaminases.

PMID- 1998687
TI  - Elucidation of the order of oxidations and identification of an intermediate in
      the multistep clavaminate synthase reaction.
AB  - The enzyme clavaminate synthase (CS) catalyzes the formation of the first
      bicyclic intermediate in the biosynthetic pathway to the potent beta-lactamase
      inhibitor clavulanic acid. Our previous work has led to the proposal that the
      cyclization/desaturation of the substrate proclavaminate proceeds in two
      oxidative steps, each coupled to a decarboxylation of alpha-ketoglutarate and a
      reduction of dioxygen to water [Salowe, S. P., Marsh, E. N., & Townsend, C. A.
      (1990) Biochemistry 29, 6499-6508]. We have now employed kinetic isotope effect
      studies to determine the order of oxidations for CS purified from Streptomyces
      clavuligerus. By using (4'RS)-[4'-3H,1-14C]-rac-proclavaminate, a primary T(V/K)
      = 8.3 +/- 0.2 was measured from [3H]water release data, while an alpha-secondary
      T(V/K) = 1.06 +/- 0.01 was determined from the changing 3H/14C ratio of the
      product clavaminate. Values for the primary and alpha-secondary effects of 11.9
      +/- 1.7 and 1.12 +/- 0.07, respectively, were obtained from the changing 3H/14C
      ratio of the residual proclavaminate by using new equations derived for a racemic
      substrate bearing isotopic label at both primary and alpha-secondary positions.
      Since only the first step of consecutive irreversible reactions will exhibit a
      V/K isotope effect, we conclude that C-4' is the initial site of oxidation in
      proclavaminate. As expected, no significant changes in the 3H/14C ratio of
      residual substrate were observed with [3-3H,1-14C]-rac-proclavaminate. However,
      two new tritiated compounds were produced in this incubation, apparently the
      result of isotope-induced branching brought about by the presence of tritium at
      the site of the second oxidation. One of these compounds was identified by
      comparison to authentic material as dihydroclavaminate, a stable intermediate
      that normally remains enzyme-bound. On the basis of the body of information
      available and the similarities to alpha-ketoglutarate-dependent dioxygenases, a
      comprehensive mechanistic scheme for CS is proposed to account for this unusual
      enzymatic transformation.

PMID- 1998688
TI  - Stabilization of non-bilayer structures by the etherlipid ethanolamine
      plasmalogen.
AB  - The thermotropic phase behavior of mixtures between
      diradylphosphatidylethanolamines and diacylphosphatidylcholine was studied using
      polarized light microscopy, 31P-NMR spectroscopy and synchrotron X-ray
      diffraction. Multilamellar liposomes composed of
      alkenylacylphosphatidylethanolamine (ethanolamine plasmalogen) undergo a phase
      transition from a lamellar to an inverse hexagonal lipid structure at 30 degrees
      C, which is about 20 degrees C and 30 degrees C lower as compared to its
      alkylacyl- and diacyl-analog, respectively. These results indicate a higher
      affinity to non-bilayer structures for the ether lipids. In the presence of the
      bilayer stabilizing phospholipid, palmitoyloleoylphosphatidylcholine, the
      transition is shifted to higher temperature without any significant changes in
      the overall structural parameters as revealed by X-ray diffraction experiments.
      Again, ethanolamine plasmalogen stabilizes the inverted hexagonal phase to the
      highest extent, i.e. even in the presence of 40 mol%
      palmitoyloleoylphosphatidylcholine a pure inverse hexagonal phase is formed at 60
      degrees C. Such a result was not reported so far for a
      diacylphosphatidylethanolamine. This property of ethanolamine plasmalogen might
      be predominantly explained by an optimized packing of the hydrocarbon chains in
      the corners and interface region of the hexagonal tubes, owing to a different
      conformation of the sn-2 chain, which was deduced from 2H-NMR experiments
      (Malthaner, M., Hermetter, A., Paltauf, F. and Seelig, J. (1987) Biochim.
      Biophys. Acta 900, 191-197). Data obtained by time resolved X-ray diffraction
      show a coexistence of lamellar and inverse hexagonal structures in the phase
      transition region, but do not indicate the existence of non-lamellar
      intermediates or disorder within the sensitivity limits of the method.

PMID- 1998690
TI  - Reconstitution of the L-leucine-H+ cotransporter of the plasma membrane from
      Chang liver cells into proteoliposomes.
AB  - L-Leucine is cotransported with H+ in the plasma membrane of Chang liver cells
      (Mitsumoto, Y. et al. (1986) J. Biol. Chem. 261, 4549). The leucine transport
      system was solubilized from the plasma membrane of the cells with ocytl glucoside
      and reconstituted in proteoliposomes prepared by a rapid dilution of a mixture of
      the solubilized proteins, octyl glucoside and liposomes. The proteoliposomes
      exhibited H(+)-gradient and electrical potential-stimulated leucine uptake. The
      H(+)-gradient-stimulated leucine uptake could be completely inhibited by carbonyl
      cyanide p-trifluoro-methoxyphenylhydrazone (FCCP) and 2
      aminobicyclo[2,2,1]heptane-2-carboxylic acid (BCH). The stimulatory effect of H+
      gradient on leucine uptake was shown to be mainly due to decrease of the Km, but
      not to change of the Vmax, of the transport kinetics. These results suggest that
      the leucine-H+ cotransporter is solubilized and reconstituted into
      proteoliposomes.

PMID- 1998689
TI  - Fluidity and lipid composition of oat and rye shoot plasma membrane: effect of
      sterol perturbation by xenobiotics.
AB  - Oat and rye plants were treated with either tetcyclacis (an experimental plant
      growth regulator), nuarimol (a fungicide) or gamma-ketotriazole (an experimental
      herbicide). These treatments reduced shoot growth and changed the lipid
      composition of the shoot plasma membranes. In oat, both tetcyclacis and nuarimol
      treatments increased plasma membrane cholesterol and increased the
      phosphatidylethanolamine/phosphatidylcholine (PE/PC) ratio, whereas gamma
      ketotriazole treatment reduced cholesterol and the PE/PC ratio. In rye, all
      treatments reduced the PE/PC ratio. Generally, the sterol/phospholipid ratio was
      less in oat than in rye but the cholesterol/phospholipid ratio was greater. With
      all treatments in oat and rye, increases were observed in unsaturation of the
      phospholipid acyl chains. The fluidity of membranes was measured by steady-state
      fluorescence polarisation of the probe diphenylhexatriene; oat membranes were
      more fluid than rye. Membrane fluidity was greater in plasma membranes from
      plants treated with the xenobiotics than the controls. The results are discussed
      in the context of the effect of plasma membrane lipid composition on membrane
      fluidity, and it is concluded that there appears to be no overall simple
      relationship between membrane lipid composition and fluidity that holds for all
      treatments in both species.

PMID- 1998691
TI  - Reversible disc-micellization of dimyristoylphosphatidylcholine bilayers induced
      by melittin and [Ala-14]melittin.
AB  - The properties of melittin and a synthetic analogue, [Ala-14]melittin (P14A), in
      inducing reversible transitions between vesicles and micelles at the liquid
      crystalline to gel phase transition temperature (Tm) in complexes with saturated
      phosphatidylcholines has been studied by deuterium NMR and freeze-fracture
      electron microscopy (EM). At concentrations between 3 and 5 mol% relative to
      lipid, each peptide causes reversible micellization of
      dimyristoylphosphatidylcholine (DMPC) bilayers when the temperature is lowered
      below Tm. At concentrations of 5 mol% relative to lipid, the peptides induce
      macroscopic magnetic orientation of DMPC bilayers at temperatures around the
      centre of the lipid phase transition; at temperatures a few degrees above Tm,
      magnetic orientation is lost. These effects suggest a progressive phase
      separation of peptide and lipid on cooling the complexes through the phase
      transition, resulting in increased vesicle deformability. The rates of gel phase
      micellization, and of bilayer reformation from micelles at temperatures above Tm,
      are decreased by 100-fold in P14A:DMPC complexes compared with melittin: DMPC
      complexes. Freeze-fracture EM indicates that P14A suppresses the formation of the
      gel phase in DMPC bilayers at temperatures below Tm. EM observations of the time
      dependence of the reformation of bilayers from micelles after incubating
      P14A:DMPC micellar complexes at temperatures above Tm indicate that micelles fuse
      to form growing bilayer sheets from which multilamellar vesicles eventually form.
      The presence of intramembranous particles (IP) on the fracture faces of both
      melittin: DMPC complexes and P14A:DMPC complexes in the fluid phase indicates
      that under the conditions of the study (50 mM Tris-HCl (pH 7.5), 5 mM EDTA) the
      peptides are organized as discrete aggregates that penetrate deeply into the
      bilayer.

PMID- 1998692
TI  - Lipid changes of goat sperm plasma membrane during epididymal maturation.
AB  - Highly purified plasma membranes of maturing goat caput-, corpus- and cauda
      epididymal spermatozoa were isolated by aqueous two-phase polymer methods and
      their lipid constituents were analysed. Phospholipid (approx. 75% w/w), neutral
      lipid (approx. 15% w/w) and glycolipid (approx. 10% w/w) were the major sperm
      membrane lipids. There was a significant decrease in the total lipids (approx.
      25% w/w), phospholipid (approx. 30% w/w) and glycolipid (approx. 80% w/w)
      contents of sperm membrane during epididymal maturation. On the contrary, the
      mature cauda-sperm membrane showed greater (approx. 50% w/w) neutral lipid
      content than that of the immature caput sperm. Phosphatidylcholine (PC),
      phosphatidylethanolamine (PE) and sphingomyelin were the phospholipids of the
      sperm membrane, the former two being the major lipids. Both PC and PE fractions
      consisted of three species--diacyl, alkylacyl and alkenylacyl forms, the last one
      being the dominant species in both PC and PE. Of all the phospholipids, diacyl PE
      decreased most strikingly (approx. 65% w/w) during sperm maturation. The neutral
      lipid fraction contained sterols, wax esters, 1-O-alkyl-2,3-diacylglycerol,
      triacylglycerol and fatty acids. Sterols represented nearly 75% w/w of the
      neutral lipids and cholesterol was the major component (approx. 95% w/w) of the
      sterol fraction. The sperm maturity was associated with marked increase of sterol
      (approx. 60% w/w) and steryl ester (approx. 200% w/w) and decrease (approx. 50
      65% w/w) of the other membrane-bound neutral lipids. The glycolipid was
      identified as monogalactosyldiacylglycerol. The fatty acid profile of the various
      membrane lipids underwent marked alteration during the epididymal transit of the
      male gametes. Cholesterol/phospholipid and saturated/unsaturated fatty acid
      ratios increased greatly in the maturing sperm membrane. The altered lipid
      profile of the mature sperm membrane leads to changes in its fluidity that play
      an important role in determining the structure and functions of the biomembrane.

PMID- 1998693
TI  - Location and regulation of octameric mitochondrial creatine kinase in the contact
      sites.
AB  - Differential extraction of creatine kinase activity (CK, EC 2.7.3.2) from rat
      brain mitochondria by graded concentrations of digitonin all yielded supernates
      varying in CK activity. As analyzed by isozyme electrophoresis and gel permeation
      chromatography the extracts contained different species of creatine kinase: (i)
      one third of the total CK activity consisting of contaminating cytosolic brain
      type CK (B-CK) was liberated by 100 micrograms digitonin/mg of mitochondrial
      protein, (ii) approx. 20% more CK activity consisting of B-CK, as above, plus
      dimeric and octameric mitochondrial CK (Mi-CK), was extracted by 300
      micrograms/mg digitonin, whereas (iii) all CK activity, consisting of B-CK and
      mainly octameric Mi-CK, were liberated by 700 micrograms/mg digitonin. In
      contrast to Mi-CK, B-CK associated with contaminating synaptic vesicles was
      readily extracted even by low concentrations of digitonin, but on the other hand
      octameric Mi-CK was significantly more resistant to digitonin extraction than the
      dimeric enzyme species. It appeared that the Mi-CK resistant to treatment with
      300 micrograms/mg digitonin consisted to a large percentage of octamers and was
      organized as a complex between the two envelope membranes, for its activity was
      latent and still remained regulated by the outer membrane pore, that is: (i) the
      Mi-CK activity in such mitoplasts could be inhibited reversibly by cessation of
      the adenine nucleotide transport through the outer membrane pore with a
      polyanion, (ii) the ADP produced by Mi-CK in mitoplasts was not available to
      external pyruvate kinase, (iii) approx. 50% of total CK activity was not
      susceptible to inhibition by iodo acetate and phosphocreatine. In agreement with
      these findings a preferential association of octameric Mi-CK was also found in
      isolated contact site fractions indicating a physiological role of Mi-CK in
      energy transfer and a structure-function relationship of Mi-CK octamers at these
      sites. In addition some evidence for an interaction of Mi-CK with the adenylate
      translocator is presented.

PMID- 1998694
TI  - Effect of chronic acid loading on rat renal basolateral membrane bicarbonate
      transport.
AB  - The effect of chronic acid loading on the activity of luminal membrane Na(+)-H+
      exchange and basolateral membrane Na+/HCO3- cotransport and Cl(-)-HCO3- exchange
      was investigated using membrane vesicles isolated from rat renal cortex. Na(+)-H
      exchange activity was increased approx. 50% in brush-border membranes isolated
      from acidemic compared to control kidneys. Na+/HCO3- cotransport and Cl(-)-HCO3-
      exchange activity was increased approx. 45% and 100%, respectively, in
      basolateral membranes isolated from acidemic kidneys. The increased Na+/HCO3-
      cotransport activity resulted from an increased apparent maximal rate of
      transport (Vmax) with no change in affinity (Km) for Na+. In contrast to
      acid/base transport activities chronic acid loading had no effect on the activity
      of basolateral membrane Na+/dicarboxylate cotransport. These results suggest
      proximal tubule cells coordinately increased luminal and basolateral membrane
      acid/base transport activities to accommodate an adaptive increase in the
      capacity for transcellular bicarbonate reabsorption.

PMID- 1998695
TI  - The effect of salinity on the phase behaviour of total lipid extracts and binary
      mixtures of the major phospholipids isolated from a moderately halophilic
      eubacterium.
AB  - The effects of molar NaCl concentrations on the phase behaviour of the total
      lipid extracts and binary mixtures of the major phospholipids, namely
      phosphatidylethanolamine (PE) and phosphatidylglycerol (PG), isolated from the
      moderately halophilic eubacterium, Vibrio costicola, grown in 1 M and 3 M NaCl
      containing media have been studied using X-ray diffraction and freeze-fracture
      electron microscopy. The effect of both the PE/PG ratio and alterations in fatty
      acid composition were examined by using binary mixtures which mimicked the PE/PG
      ratio found in the native bacterial membranes. We show that the samples exhibited
      complex phase behaviour, including the formation of non-bilayer phases, which
      depend upon the salinity of both the bacterial culture medium and the suspending
      solution. The total lipid from bacteria cultured in 1 M NaCl-containing medium
      and dispersed in 1 M NaCl exhibited a mixture of L alpha and hexagonal-II phases
      at the optimum growth temperature of the organism (i.e., 30 degrees C), whereas
      the same lipid dispersed in 3 M NaCl showed only a hexagonal-II phase down to a
      temperature of +3 degrees C. The total lipid extracted from 3 M NaCl cultures
      showed only lamellar phases over the temperature range studied (+50 degrees C to 
      50 degrees C), but the phase transition temperatures of the various lamellar
      phases were generally higher when the lipid was dispersed in 3 M compared with 1
      M NaCl. The phase behaviour of the binary mixtures was similar but not identical
      to that of the corresponding total lipid extracts and it is suggested that the
      minor lipid components (diphosphatidylglycerol, lysophosphatidylethanolamine and
      lysophosphatidylglycerol) play a part in determining the phase behaviour of the
      native membranes. These results show that the PE/PG ratio and fatty acid
      composition of the individual phospholipids, which are normally regulated by
      Vibrio costicola in vivo in response to culture medium salinity, are both
      important in maintaining a stable bilayer structure within the membrane.

PMID- 1998696
TI  - The sodium-calcium exchanger of bovine rod photoreceptors: K(+)-dependence of the
      purified and reconstituted protein.
AB  - The K(+)-dependence of the rod photoreceptor sodium-calcium exchanger was
      investigated using the Ca2(+)-sensitive dye arsenazo III after reconstitution of
      the purified protein into proteoliposomes. The uptake of Ca2+ by Na(+)-loaded
      liposomes was found to be greatly enhanced by the presence of external K+ (EC50
      approximately 1 mM) in a Michaelis-Menten manner, suggesting that one K+ ion is
      involved in the transport of one Ca2+ ion. We also found a minimal degree of Ca2+
      uptake in the total absence of K+. Other alkali cations, notably Rb+ and, to a
      lesser extent, Cs+, were also able to stimulate Na(+)-Ca2+ exchange. We also
      investigated the K(+)-dependence of the photoreceptor Na(+)-Ca2+ exchanger by
      determining the effects of electrochemical K+ gradients on the Na(+)-activated
      Ca2+ efflux from proteoliposomes. We found that, under conditions of membrane
      voltage clamp with FCCP, inwardly directed electrochemical K+ gradients (i.e.,
      K0+ greater than Ki+) inhibited, whereas an outwardly directed electrochemical K+
      gradient (i.e., Ki+ greater than K0+) enhanced, Na(+)-dependent Ca2+ efflux,
      consistent with the notion that K+ is cotransported in the same direction as
      Ca2+. The investigation of the reconstituted exchanger at physiological (i.e. Ki+
      = 110 mM, K0+ = 2.5 mM) potassium concentrations revealed that the Na(+)
      dependence of Ca2(+)-efflux was highly cooperative (n = 3.01 from Hill plots),
      indicating that at least three, but possibly four, Na+ ions are exchanged for one
      Ca2+ ion. Under these conditions the reconstituted exchanger showed a Km for Na+
      of 26.1 mM, and a turnover number of 115 Ca2+.s-1 per exchanger molecule. Our
      results with the purified and reconstituted sodium-calcium exchanger from rod
      photoreceptors are therefore consistent with previous reports (Cervetto, L.,
      Lagnado, L., Perry, R.J., Robinson, D.W. and McNaughton, P.A. (1989) Nature 337,
      740-743; Schnetkamp, P.P.M., Basu, D.K. and Szerencsei, R.T. (1989) Am. J.
      Physiol. 257, C153-C157) that the sodium-calcium exchanger of rod photoreceptors
      cotransports K+ under physiological conditions with a stoichiometry of 4 Na+:1
      Ca2+, 1K+.

PMID- 1998697
TI  - Phosphorylation sites in human erythrocyte band 3 protein.
AB  - The human red cell anion-exchanger, band 3 protein, is one of the main
      phosphorylated proteins of the erythrocyte membrane. Previous studies from this
      laboratory have shown that ATP-depletion of the red blood cell decreased the
      anion-exchange rate, suggesting that band 3 protein phosphorylation could be
      involved in the regulation of anion transport function (Bursaux et al. (1984)
      Biochim. Biophys. Acta 777, 253-260). Phosphorylation occurs mainly on the
      cytoplasmic domain of the protein and the major site of phosphorylation was
      assigned to tyrosine-8 (Dekowski et al. (1983) J. Biol. Chem. 258, 2750-2753).
      This site being very far from the integral, anion-exchanger domain, the aim of
      the present study was to determine whether phosphorylation sites exist in the
      integral domain. The phosphorylation reaction was carried out on isolated
      membranes in the presence of [gamma-32P]ATP and phosphorylated band 3 protein was
      then isolated. Both the cytoplasmic and the membrane spanning domains were
      purified. The predominant phosphorylation sites were found on the cytoplasmic
      domain. RP-HPLC analyses of the tryptic peptides of whole band 3 protein, and of
      the isolated cytoplasmic and membrane-spanning domains allowed for the precise
      localization of the phosphorylated residues. 80% of the label was found in the N
      terminal tryptic peptide (T-1), (residues 1-56). In this region, all the residues
      susceptible to phosphorylation were labeled but in varying proportion. Under our
      conditions, the most active membrane kinase was a tyrosine kinase, activated
      preferentially by Mn2+ but also by Mg2+. Tyrosine-8 was the main phosphate
      acceptor residue (50-70%) of the protein, tyrosine-21 and tyrosine-46 residues
      were also phosphorylated but to a much lesser extent. The main targets of
      membrane casein kinase, preferentially activated by Mg2+, were serine-29, serine
      50, and threonine(s)-39, -42, -44, -48, -49, -54 residue(s) located in the T-1
      peptide. A tyrosine phosphatase activity was copurified with whole band 3 protein
      which dephosphorylates specifically P-Tyr-8, indicating a highly exchangeable
      phosphate. The membrane-spanning fragment was only faintly labeled.

PMID- 1998698
TI  - Small-volume extrusion apparatus for preparation of large, unilamellar vesicles.
AB  - The design and performance of a filter holder which enables convenient
      preparation of volumes of up to a milliliter of large, unilamellar vesicles
      formed by extrusion (LUVETs) from multilamellar vesicles (MLVs) are described.
      The filter holder provides for back-and-forth passage of the sample between two
      syringes, a design that minimizes filter blockage, eliminates the need to change
      filters during LUVET preparation and reduces preparation time to a few minutes.
      Replicas of slam-frozen LUVETs in the electron microscope are unilamellar and
      reasonably homogeneous with an average diameter close to the pore size of the
      filters used to extrude them. Extrusion per se does not destabilize the vesicles,
      which trapped a fluorescent dye only when they were disrupted on freeze-thawing
      and during the first extrusion when most of the MLVs were apparently converted to
      LUVETs.

PMID- 1998700
TI  - Water transport in human red cells: effects of 'non-inhibitory' sulfhydryl
      reagents.
AB  - The water diffusional permeability of human red blood cells following exposure to
      various sulfhydryl group (SH) reagents have been studied using a nuclear magnetic
      resonance technique. Exposure of red blood cells up to 12 mM N-ethylmaleimide
      (NEM) or 10 mM 5,5'-dithio-bis(2-nitrobenzoic acid) (DTNE) alone does not affect
      water diffusion. In contrast, when DTNB treatment follows a preincubation of the
      cells with NEM, a small (18% at 37 degrees C) but significant inhibition of water
      permeability occurs. The NEM and DTNB treatment of the cells caused no change of
      the cell shape and volume or of the cell water volume. Consequently, the
      inhibition observed after NEM and DTNB treatment has a real significance.

PMID- 1998699
TI  - Characteristics of 86Rb+ transport in human erythrocytes infected with Plasmodium
      falciparum.
AB  - Human red cells infected in vitro with Plasmodium falciparum showed a significant
      increase in the rate of both ouabain-sensitive and ouabain-insensitive 86Rb+
      influx. The increase in ouabain-insensitive 86Rb+ influx was due, in part, to
      increased transport via a bumetanide-sensitive system and, in part to transport
      via a pathway that was absent (or at least inactive) in uninfected cells. The
      parasite-induced pathway was inhibited by piperine and had a dose response very
      similar to that of the Gardos channel of uninfected cells but was less sensitive
      than the Gardos channel to inhibition by quinine.

PMID- 1998701
TI  - Analysis of the chainlength dependence of lipid phase transition temperatures:
      main and pretransitions of phosphatidylcholines; main and non-lamellar
      transitions of phosphatidylethanolamines.
AB  - The dependence on chainlength, n, of the temperatures at which the various
      thermotropic phase transitions in phospholipid bilayers take place can be fitted
      to high accuracy with an expression of the form: Tt = Tt infinity (1-A/(n-d))
      where Tt infinity, A and d are the constants to be fitted. This expression works
      well with literature values for the main and pretransitions of saturated straight
      chain phosphatidylcholines, for the main transition of isobranched- and
      anteisobranched-chain phosphatidylcholines, and for the main and non-lamellar
      phase transitions of saturated straight-chain phosphatidylethanolamines, and also
      for diacylglycerol glycolipids. The parameters in the fit can be related
      thermodynamically to the calorimetric properties of the phase transition. The
      constants A and d are related to the end effects in the chainlength dependence of
      the transition enthalpy and transition entropy, respectively, and the transition
      temperature extrapolated to infinite chainlength, Tt infinity, is determined by
      the ratio of the incremental transition enthalpy and transition entropy per
      methylene group. A reasonable correspondence is found between the chainlength
      dependence of the transition temperature and of the transition enthalpy and
      transition entropy for saturated straight-chain diacylphosphatidylcholines. It is
      likely, however, that the expression for the chainlength dependence of the
      transition temperature may be of more general applicability, because, on the one
      hand of the greater inherent precision of the transition temperature
      measurements, and on the other hand because the expression for the transition
      temperature is of more general validity, provided that the chainlength dependence
      of the incremental transition enthalpy and entropy are the same.

PMID- 1998702
TI  - Core-coat conductor of lipid bilayer and micromachined silicon.
AB  - We have etched a groove into a (110) plane of silicon and have covered it with a
      bilayer of glycerol monooleate. We have varied the depth of the groove, the
      concentration of salt in the electrolyte and the density of gramicidin in the
      membrane. We have clamped one end of the groove at a constant voltage with
      respect to the bath keeping the other end sealed or electrically open with
      respect to the bath. We have measured (i) the voltage at the center of the groove
      and at the sealed distal end and (ii) the current through the system in sealed
      and open configuration. We have found that the spread of voltage is in
      quantitative agreement with the stationary solutions of Kelvin's equation for a
      homogeneous cable.

PMID- 1998703
TI  - Size and stability of dipalmitoylphosphatidylcholine/cholesterol unilamellar
      vesicles are affected by interaction with proteins.
AB  - The effect of entrapping the enzyme ascorbate oxidase into
      dipalmitoylphosphatidylcholine/cholesterol vesicles, was studied by conventional
      transmission electron microscopy and freeze-fracture. The freeze-fracture
      technique has definitely demonstrated the unilamellar nature of empty and enzyme
      loaded vesicles. Images of freeze-fractured and label-fractured liposomes also
      indicate that the observed reduction of vesicles volume could be related to the
      localization of ascorbate oxidase across the membrane. The membrane localization
      of ascorbate oxidase may explain the oxidation of externally added ascorbate by
      intact enzyme-loaded liposomes. Finally, the ageing of liposomes appears to be
      accelerated in the presence of proteins.

PMID- 1998704
TI  - Further evidence for a simple Cl- conductance pathway in nutrient membrane of
      frog stomach.
AB  - A decrease in nutrient Cl- increases the negativity of the nutrient relative to
      the secretory side. It seemed possible that Cl- transport could result from a
      neutral Cl- mechanism in the nutrient membrane coupled to a simple Cl-
      conductance pathway in the secretory membrane. Experiments in HCO3(-)-free, K(+)
      free and Na(+)-free solutions in both bathing media gave for a 10-fold change in
      nutrient Cl- a PD change of 9.5 mV. Similar experiments with 0.5 mM DIDS in the
      nutrient solution gave for a 10-fold change in nutrient Cl- a PD change of 7.9
      mV. These experiments eliminated a neutral Cl(-)-HCO3- exchanger, a NaCl and a
      KCl symport. Thus the change in PD could best be explained by a simple Cl-
      conductance in the nutrient membrane.

PMID- 1998705
TI  - Selection of hybrid plants obtained by electrofusion of vacuolated x evacuolated
      plant protoplasts in hypo-osmolar solution.
AB  - Vacuolated and evacuolated tobacco mesophyll protoplasts were electrically fused
      in hypo-osmolar media by using an alternating field of modulated amplitude for
      alignment. The vacuolated fusion partner was isolated from Nicotiana tabaccum L.
      cv Xanthi and the evacuolated one from the streptomycin-resistant strain
      Nicotiana tabaccum L. cv Petit Havana SR1. The field and osmolarity conditions
      used ensured relatively high yields of heterologous fusion products despite the
      differences in density and size of the parental cells. After removal of the
      evacuolated, streptomycin-resistant fused and unfused protoplasts by flotation of
      vacuole-containing cells on iso-osmolar sucrose medium, the cybrids and hybrids
      were cultured in 25 microliters drops of agarose. During the first 5 weeks the
      non-fused Xanthi-protoplasts were used as a nurse culture. After addition of
      streptomycin to the growth media, cybrids and hybrids were successfully selected
      whereas fused and unfused vacuole-containing protoplasts died within 6 days. Only
      the streptomycin-resistant cybrids and hybrids developed into whole plants. On
      average a yield of 0.025% of streptomycin-resistant plants (referred to the total
      number of parental cells) was obtained. Polyacrylamide gel electrophoresis of
      leaf extracts of these plants showed that at least 50% of the streptomycin
      resistant plants had a hybrid-esterase isoenzyme pattern. The protocol can be
      generalised by fusion of iodoacetamide-inactivated vacuolated protoplasts with
      meristematic (or evacuolized) protoplasts carrying no genetic marker. Use of
      evacolated protoplasts for electrofusion with vacuole-containing protoplasts
      therefore offers a way of overcoming the lack of suitable genetic markers for
      hybrid selection.

PMID- 1998706
TI  - Effect of temperature on sodium-calcium exchange in sarcolemma from mammalian and
      amphibian hearts.
AB  - We have investigated temperature dependence of Ca2+ uptake by the cardiac
      sarcolemmal Na(+)-Ca2+ exchanger from dog, rabbit and bullfrog. In native rabbit
      sarcolemmal vesicles, Ca2+ affinity of the Na(+)-Ca2+ exchanger is unchanged from
      7 to 37 degrees C; however, the initial velocity of Ca2+ uptake declines much
      more steeply below 22 degrees C than above 22 degrees C. In native dog
      sarcolemma, the temperature dependence of Na(+)-Ca2+ exchange velocity is similar
      to that of native rabbit. However, in frog heart the velocity of Na(+)-Ca2+
      exchange declines much more slowly with decreasing temperature at both
      temperature ranges. Reconstitution of the Na(+)-Ca2+ exchanger into artificial
      lipid vesicles consisting of either asolectin or phosphatidylserine,
      phosphatidylcholine, and cholesterol has little effect on temperature dependence
      of Na(+)-Ca2+ exchange velocity in any of the three species. We conclude that the
      lesser temperature sensitivity of the cardiac sarcolemmal Na(+)-Ca2+ exchanger of
      a poikilothermic species is at least partly an intrinsic property of the
      transport protein.

PMID- 1998707
TI  - Functional expression of the CD4 protein after cross-linking to red blood cells
      with a bifunctional reagent.
AB  - We used a bifunctional reagent for the design of a new therapeutic agent
      constructed by cross-linking a soluble form of the CD4 protein to red blood cell
      membranes. CD4 is a member of the immunoglobulin gene superfamily and is the
      receptor for the AIDS virus, HIV. We produced soluble CD4 in eucaryotic cells
      transfected with a soluble CD4 expression vector, and purified it by cation
      exchange chromatography. Flow cytometry studies demonstrated that CD4-coated red
      blood cells were specifically stained with an anti-CD4 monoclonal antibody,
      whereas intact red blood cells and intermediates obtained during the coupling
      procedure were not stained. By comparison, with CD4+ lymphoid cells, the number
      of soluble CD4 molecules per CD4-expressing red blood cells was estimated to be
      approx. 100,000. We present evidence that, unlike the classical chromium chloride
      coupling method, large amounts of soluble CD4 were efficiently and uniformly
      coupled to RBCs. CD4 red blood cells bind specifically HIV particles, and inhibit
      the binding of HIV particles to target cells, the initial step of HIV life cycle.
      The anti-HIV activity of CD4-bearing red blood cells was found to be at least 20
      times higher than that of free soluble CD4. Our results demonstrate that proteins
      can be efficiently coupled to red blood cells using bifunctional reagents. They
      also suggest that CD4-coated RBC are promising CD4-based anti-HIV agents.

PMID- 1998708
TI  - Mechanism of hemolysis of red blood cell mediated by ethanol.
AB  - The effects of ethanol on hemolysis of human red blood cells (RBCs) were studied
      at 21 +/- 1 degrees C in the saline buffer (138 mM NaCl, 6.1 mM Na2HPO4, 1.4 mM
      NaH2PO4, 5 mM glucose and pH 7.4). The hemolysis process for ethanol-treated RBCs
      was preceded by the leakage of the small cation K+ from the cells indicating the
      colloid-osmotic nature of lysis. Since the extent of membrane lesion increased
      with an increasing ethanol concentration, osmotic protection experiments by using
      solutes varying in size were carried out to estimate the diameter of the pore.
      Quantitative analysis of the data by considering the effect of molecular seiving
      of the protectants with different sizes indicated that ethanol induced formation
      of membrane pores with a diameter of approximately 13 A. There was no detectable
      release of membrane fragments as assayed by the acetylcholinesterase activity,
      but the membrane structures were significantly perturbed, presumably at the
      membrane cytoskeletal protein, as evidenced by the altered rheological properties
      of RBC in the presence of ethanol. It is suggested that the creation of membrane
      pores might involve in the deranged cytoskeletal network of ethanol-treated RBC.

PMID- 1998709
TI  - Long-term intercalation of residual hemin in erythrocyte membranes distorts the
      cell.
AB  - The effect of long-term incubation of residual globin-free hemin on whole red
      blood cell and isolated cytoskeletal proteins was studied. Hemin at
      concentrations found in pathological red cells was inserted to fresh
      erythrocytes. Increased hemolysis developed in the hemin-containing cells after a
      few days at 37 degrees C and after about four weeks at 4 degrees C. Since lipid
      and hemoglobin peroxidation did not depend on the presence of hemin, time
      dependent effects on the cytoskeleton proteins were studied. Observations were:
      (1) spectrin and protein 4.1 exhibited a time-dependent increasing tendency to
      undergo hemin-induced peroxidative crosslinking. (2) The ability of the serum
      proteins, albumin and hemopexin, to draw hemin from spectrin, actin and protein
      4.1 decreased with time of incubation with hemin. These results were attributed
      to time-dependent hemin-induced denaturation of the cytoskeletal proteins.
      Albumin taken as a control for physiological hemin trap was unaffected by hemin.
      Small amounts of hemo-spectrin (2-5%) were analyzed in circulating normal cells,
      and this in vivo hemo-spectrin also failed to release hemin. It was concluded
      that slow accumulation of hemin, a phenomenon increased in pathological cells, is
      a toxic event causing erythrocyte destruction.

PMID- 1998710
TI  - Polymorphism of the bilayer membranes in the ordered phase and the molecular
      origin of the lipid pretransition and rippled lamellae.
AB  - The lamellar-to-undulated-lamellar phase transition (L beta'----P beta',
      pretransition) in lipid bilayers is shown to be a phenomenon which exists only if
      lipid polar headgroups are sufficiently hydrated and if the interchain packing is
      sufficiently weak. The minimal lipid hydrophilicity and the critical amount of
      the lipid-bound water can be related to the lipid chain-melting transition
      temperature; the latter must not exceed some maximal, chainlength-dependent value
      if the pretransition is to exist. The minimally required amount of the lipid
      bound water itself is essentially chainlength independent, however, and
      unaffected by the method of hydration variation: physical dehydration,
      hydrational competition between the lipid molecules and the substances dissolved
      in the aqueous subphase, or decreasing lipid headgroup polarity all affect the
      pretransition temperature similarly on the appropriate scale. Simple,
      phenomenological expressions for the evaluation of the bilayer subtransition,
      pretransition and chain-melting phase transition temperature as a function of the
      lipid chainlength are presented. They show that, even in excess water, bilayers
      will tend to undulate only as long as each of the two identical lipid chains will
      contain between 12 +/- 1 and 22 +/- 1 carbon atoms, the P beta-phase region for
      the less polar lipids being as a rule narrower. To get a theoretical means for
      quantitatively studying the effects of the lipid hydration on the bilayer
      pretransition, an interaction-balance method is proposed for describing undulated
      membranes at the molecular level. This is based on comparing the free-energy gain
      from the increased headgroup hydration with the free-energy loss caused by the
      reduced chain-chain attraction upon ripple formation. A rationale is thus found
      for scaling the pretransition temperature in terms of the hydration-induced chain
      melting phase transition shift or of the lipid surface hydrophilicity. Within the
      framework of such a model the recently reported (de)hydration dependence of the
      bilayer-undulation period is reproduced with reasonable accuracy. Furthermore, it
      is estimated that at least 12 +/- 2 water molecules must be associated with each
      lipid head for the bilayer undulation to be feasible. The closer the system is to
      this boundary condition the longer is the repeat-distance for the surface
      undulations and the less stable is the undulated bilayer phase.

PMID- 1998711
TI  - Liposomes having high sensitivity to odorants.
AB  - The conditions to increase the sensitivities of liposomes to odorants were
      examined. The results obtained are as follows. (1) The minimum concentration of
      amyl acetate to induce the membrane potential changes (threshold) in
      phosphatidylcholine (PC) liposomes was about 10(-4) M and addition of 10 or 20%
      phosphatidylserine (PS) lowered the threshold to about 10(-9) M, which was lower
      than the thresholds for amyl acetate in the turtle and frog olfactory systems.
      (2) Similar to amyl acetate, addition of PS to PC greatly lowered the threshold
      for beta-ionone. On the other hand, addition of PS to PC in certain ratio
      increased the threshold for citral, suggesting that addition of PS to PC does not
      always increase the responses to all odorants. (3) The membrane fluidity change
      of the liposomes in response to odorants occurred at similar concentration region
      where the membrane potential changes occurred. The presence of CaCl2 in external
      solution much greatly increased both the magnitude of the membrane potential
      changes and the membrane fluidity changes of the PC-PS liposomes in response to
      amyl acetate than the presence of NaCl and MgCl2. These results suggest that the
      membrane fluidity change is related to generation of the membrane potential
      change. (4) It was estimated that adsorption of less than a few molecules of amyl
      acetate on single liposome elicits detectable changes in the membrane potential
      and the membrane fluidity.

PMID- 1998712
TI  - Cholesterol does not remove the gel-liquid crystalline phase transition of
      phosphatidylcholines containing two polyenoic acyl chains.
AB  - Homoacid (single-acid) phosphatidylcholines containing two linoleate (18:2),
      arachidonate (20:4), or docosahexaenoate (22:6) chains were dispersed in water to
      form multilamellar vesicles. The influence of cholesterol on the gel to liquid
      phase transitions was studied by differential scanning calorimetry (DSC). The
      pure dipolyenoic phosphatidylcholines exhibited very broad endothermic
      transitions (widths of 28 to 38 C degrees at scanning rates of 5 C degrees/min)
      in the temperature range of about -80 degrees C to -30 degrees C. The mixing of
      cholesterol into the phospholipids in proportions up to 50 mol% had little effect
      on the temperatures, widths or enthalpy changes associated with the phase
      transitions. The data suggest that cholesterol does not interfere with the
      packing of these lipids in the gel state, possibly because the packing is already
      irregular or because the solubility of cholesterol in these lipids is low, or
      both.

PMID- 1998713
TI  - Influence of surface hydrophilicity of liposomes on their interaction with plasma
      protein and clearance from the circulation: studies with poly(ethylene glycol)
      coated vesicles.
AB  - Well-defined liposome systems have previously established the influence of size,
      surface charge lipid composition and surface ligands, on in vivo fate and
      behaviour of model compounds entrapped in liposomes. In the present study,
      preformed liposomes which quantitatively retain aqueous markers were covalenty
      coupled via dipalmitoylphosphatidyl-ethanolamine, to the hydrophilic polymer,
      monomethoxypoly(ethylene glycol) (MPEG 5000). Such liposomes retain the coating
      in the presence of plasma, and appear to adsorb plasma components more slowly
      than liposomes without the polymer, shown using an aqueous two-phase partitioning
      technique. MPEG-coupled liposomes were cleared from the blood circulation up to
      30% more slowly than liposomes without MPEG after intravenous administration to
      mice, despite the unmodified liposomes being of a composition and size shown
      previously to favour achievement of maximum half-life. It is suggested that the
      polymer acts as a surface barrier to plasma factors which otherwise bind to
      liposomes in the blood and accelerate vesicle removal.

PMID- 1998714
TI  - Glucose transport kinetics in human red blood cells.
AB  - D-[14C]Glucose self exchange and unidirectional efflux from human red blood cells
      were studied at 20 degrees C (pH 7.2) by means of the Millipore-Swinnex filtering
      technique whose time resolution is greater than 1 s and the continuous flow-tube
      method with a time resolution of greater than 2 ms. The unidirectional efflux
      data were analyzed using both the method of initial rates and the integrated rate
      equation. Simple Michaelis-Menten kinetics apply to the results obtained under
      both experimental conditions. In self-exchange mode, the half-saturation
      constant, K1/2ex, was 10 (S.E. +/- 1) mM. In unidirectional efflux mode K1/2ue
      was 6.6 (S.E. +/- 0.5) mM (initial rates) or by the method of integrated rates
      7.7 mM, with a range of 2.7-12.1 mM, K1/2ue increasing with an increased initial
      intracellular glucose concentration. Our results of K1/2ex oppose previous
      published values of 32 mM for self exchange (Eilam and Stein (1972) Biochim.
      Biophys. Acta 266, 161-173) and 25 mM for unidirectional efflux (Karlish et al.
      (1972) Biochim. Biophys. Acta 255, 126-132) that have been used extensively in
      kinetic considerations of glucose transport models. Under self-exchange
      conditions Jmaxex was 1.8 x 10(-10) mol cm-2s-1, and in unidirectional efflux
      mode Jmaxue was 8.3 x 10(-11) mol cm-2s-1 (initial rates) and 8.6 x 10(-11) mol
      cm-2s-1 (integrated rates). We suggest that the previous high values of Jmax and
      in particular K1/2 are due to the use of methods with insufficient time
      resolution. Our results indicate that the transport system is less asymmetric
      than was generally accepted, and that complicated transport models developed to
      account for the great difference between the determined K1/2 and J max values are
      redundant.

PMID- 1998715
TI  - Melittin induced voltage-dependent conductance in DOPC lipid bilayers.
AB  - Melittin-induced conductance was measured on planar bilayers made from
      dioleoylphosphatidylcholine. Upon application of a fixed voltage, the current
      response was monophasic and remained so even after prolonged observation times.
      The conductance of melittin-doped bilayers increased exponentially with voltage.
      In addition, an ohmic contribution appeared after some current had passed. The
      voltage-dependent conductance increased e-fold every 22 mV and was proportional
      to the fourth power of the aqueous monomeric peptide concentration, for all salt
      concentrations investigated (0.4-1.8 M NaCl). Discrete conductance steps could be
      resolved at all these salt concentrations. The amplitudes of these steps were
      highly variable. In each experiment, conductance was initially only observed for
      potentials which were positive on the side of peptide addition. As more and more
      current passed across the bilayer, the current-voltage curves became symmetric.
      The system needed some time to reach stationary current-voltage characteristics:
      about 50 min at pH 7 but only about 15 min at pH 8, suggesting involvement of the
      N-terminus (pK around 7.5) of melittin in the slow formation of a 'prepore'.

PMID- 1998716
TI  - Kinetic analysis of the interaction of nitric oxide with the membrane-associated,
      nickel and iron-sulfur-containing hydrogenase from Azotobacter vinelandii.
AB  - The effects of nitric oxide (NO) on the membrane-associated form of the nickel
      and iron-sulfur-containing hydrogenase from Azotobacter vinelandii have been
      investigated. In the presence of H2 and an electron acceptor (turnover
      conditions), NO acts as a noncompetitive inhibitor vs. methylene blue (Ki = 12
      microM). There is no element of competition between NO and H2, implying that the
      site of NO action is not the H2-activating site of the hydrogenase. When the
      membrane-associated hydrogenase is incubated under non-turnover conditions, the
      enzyme is irreversibly inactivated by NO in a time-dependent process. The
      inactivation is a non-saturable, pseudo-first-order process which is consistent
      with a direct chemical reaction between NO and the hydrogenase. Kinetic evidence
      is presented which is compatible with an interaction between NO and a redox
      active component other than the H2-activating site on the enzyme. The complex
      inhibition pattern of NO has been interpreted in terms of two distinct
      interactions of NO with iron-sulfur centers of the hydrogenase.

PMID- 1998717
TI  - Long range electron transfer between tyrosine and tryptophan in hen egg-white
      lysozyme.
AB  - The azide, dibromide and dichloride radicals oxidize one or more tryptophan side
      chains in hen egg-white lysozyme. The indolyl radical produced in this second
      order 1-electron oxidation subsequently oxidizes a tyrosine side chain to the
      phenoxy radical in an intramolecular reaction with a rate constant of 130 +/- 10
      s-1 at pH 7, 25 degrees C. The final indolyl and phenoxy equilibrium mixture then
      decays with a t1/2 approximately 2 s. The faster intramolecular reaction exhibits
      a pH dependence; on decreasing the pH from 9 the first-order rate constant
      increases to a maximum near pH 5.4 and then declines as the pH is lowered
      further. In contrast, the first-order rate constant for the intramolecular
      electron transfer between the tyrosine and tryptophan of the peptide trpH-pro
      tyrOH remains unchanged between approx. pH 11 and 6.5 and then increases as the
      pH is lowered further. This difference in the observed pH dependence suggests
      that changes in structure or ionization state influence the protein electron
      transfer rate. We also discuss the radiation inactivation of lysozyme in light of
      these observations.

PMID- 1998718
TI  - Chemical modification and NMR studies on a mushroom lectin Ischnoderma resinosum
      agglutinin (IRA).
AB  - Chemical modification and NMR studies on a beta-galactosyl-specific lectin which
      was isolated from the fruiting bodies of a mushroom, Ischnoderma resinosum, has
      been carried out in order to investigate the amino acid residues involved in its
      sugar-binding sites. Modification of amino groups with succinic anhydride greatly
      affected the hemagglutinating activity. Inhibitory sugar lactulose could prevent
      the loss of the activity. Modification of carboxyl groups with glycine ethyl
      ester led to a 75% loss of the activity, the presence of inhibitory sugar being
      protective against the modification. Treatment with cyclohexane-1,2-dione for
      modification of arginine residues was accompanied by a complete loss of the
      activity. The arginine residues modification could also be protected by the
      inhibitory sugar. N-Bromosuccinimide treatment for modification of tryptophan
      residues caused a loss of the activity, although the inhibitory sugar exhibited
      no protective effect against this treatment. Modification of thiol groups with
      5,5'-dithiobis(2-nitrobenzoic acid) resulted in a 50% loss of the activity.
      Modification of histidine residues with ethoxyformic anhydride led to a complete
      loss of the activity. The loss of the activity could be protected by the
      inhibitory sugar. Treatment with N-acetylimidazole for modification of tyrosine
      residues was accompanied by a loss of the activity. This modification was
      completely prevented in the presence of the inhibitory sugar. The activity of the
      tyrosine-modified lectin was recovered by the treatment with hydroxylamine.
      Furthermore, in the NOESY spectrum of the mixture of IRA and its inhibitory
      sugar, methyl beta-galactoside, an NOE cross peak between H-3 and/or 5 of the p
      hydroxyphenyl group of a tyrosine in the lectin, and H-5 of the galactoside could
      be observed. These results indicate that a tyrosine residue is involved in the
      carbohydrate-binding site of the lectin. In addition, line broadening and down
      field shifts of the galactoside-protons were observed in the presence of the
      lectin.

PMID- 1998719
TI  - Crystallization and characterization of a lectin obtained from a mushroom,
      Aleuria aurantia.
AB  - A fucose-specific lectin with a unique sugar recognizing property was purified
      from an orange peel mushroom, Aleuria aurantia, by using a specific affinity
      adsorbent prepared from L-fucose and starch. From 100 g of fruiting bodies, 145
      mg of pure lectin was obtained. The lectin was crystallized and the crystals
      showed hexagonal bipyramid in shape. Distribution of hydrophobic and hydrophilic
      regions in the molecule of this lectin was predicted from the amino acid sequence
      deduced from the previously reported nucleotide sequence of the lectin cDNA.
      Circular dichroism spectra revealed a very low content of alpha-helical and beta
      sheet structures and a relatively high content of turns in this lectin. From the
      spectrum observed in the presence of L-fucose, a hapten sugar of this lectin,
      certain conformational change was assumed to occur.

PMID- 1998720
TI  - Estradiol 17 beta-dehydrogenase: full enzymatic activity in the absence of zinc.
AB  - The precise catalytic mechanism of the steroid interconverting enzyme, human
      placental estradiol 17 beta-dehydrogenase (EC 1.1.1.62, estradiol-17 beta:NAD+ 17
      oxidoreductase), is not known. Two general models for the catalytic mechanism of
      dehydrogenases have been defined. One model requires Zn2+ metal for the catalytic
      event, as has been shown for horse liver alcohol dehydrogenase (EC 1.1.1.1,
      alcohol:NAD+ oxidoreductase). Another model has been demonstrated for the 2
      hydroxy acid dehydrogenases in which histidine residues are necessary for enzyme
      activity, without participation of a metal ion. In order to define which
      mechanism might be operative for the placental enzyme, it became important to
      determine whether Zn2+, or another metal ion, is associated with the
      macromolecule. Several homogeneous enzyme preparations, having protein
      concentrations from 5-80 microM, were extensively dialyzed in a buffer containing
      EDTA. Atomic absorption analysis of each sample demonstrated that no Zn2+ was
      present, although the enzymatic activity was maintained. In addition, there was
      no significant detection of Mg2+ or Mn2+ above background levels. When the
      isolated enzyme was dialyzed against buffer containing added 0.01-20 microM
      ZnCl2, no increase in specific activity of the enzyme was seen. The data indicate
      that the presence of zinc is not required for the catalytic event. These results,
      together with our previous affinity-labeling studies, which demonstrate a
      histidine residue in the catalytic region of the active site, allow us to propose
      that the catalytic mechanism of the human placental estradiol 17 beta
      dehydrogenase is similar to that of the 2-hydroxy acid dehydrogenases.

PMID- 1998721
TI  - Purification and molecular properties of urate oxidase from Chlamydomonas
      reinhardtii.
AB  - Urate oxidase (urate: oxygen oxidoreductase, EC 1.7.3.3) from the unicellular
      green alga Chlamydomonas reinhardtii has been purified to electrophoretic and
      immunological homogeneity by a procedure which includes as main steps ammonium
      sulfate fractionation, gel filtration, ion exchange and xanthine-agarose affinity
      chromatography. The native enzyme has a relative molecular mass (Mr) of 124,000
      and consists of four identical or similar-sized subunits of Mr 31,000 each. The
      enzyme has a Stokes's radius of 3.87 nm, a sedimentation coefficient of 6.8 S and
      an f/f0 of 1.23, and exhibits its maximal absorption at 276 nm. Optimum pH was
      8.5 and maximum activity was shown at 40 degrees C, with an activation energy of
      53 kJ.mol-1 and a Q10 of 1.96. Absorption spectrum of native reduced enzyme
      showed two transient maxima at 392 and 570 nm, very similar to those of metal
      urate complexes, which disappeared in the presence of cyanide. Inhibition by
      cyanide and neocuproin, but not by salicylhydroxamic acid, strongly suggests that
      copper is the metal involved in enzymatic urate oxidation. By using a sensitive
      photokinetic method for copper determination, a content of 4 mol of copper per
      mol of enzyme has been found.

PMID- 1998722
TI  - The primary structure of hemoglobin from reindeer (Rangifer tarandus tarandus)
      and its functional implications.
AB  - The primary structures of alpha- and beta-chains of hemoglobin from reindeer
      (Rangifer tarandus tarandus) were determined. Comparison of the reindeer
      hemoglobin sequence with those of human and bovine hemoglobins showed 50 and 29
      substitutions per alpha beta dimer, respectively. The influence of replacements
      on the modulation of hemoglobin oxygen affinity by heterothopic ligands and
      temperature, as well as their importance on the structure-function relationships
      in hemoglobin are discussed.

PMID- 1998723
TI  - The C-domain in the H1 histone is structurally conserved.
AB  - The C-domain of H1 is conserved in composition and not in sequence. The following
      regularities have been identified: the distribution of lysine, alanine and
      proline is non-random; alanine occurs in doublets and at intervals of 4-6
      significantly more often than expected for random sequences of equal composition;
      and lysine also deviates from random distribution in that doublets are under
      represented and intervals of 2-7 are over-represented. Lysine preferentially
      occurs in singlets and alanine in doublets rather than triplets or quadruplets.
      This discourages the formation of helices without neutralization of lysine
      charges. When lysine residues are paired with DNA phosphate residues, helices are
      highly probable. Interproline spacing promotes short helical segments. The
      regularities arising from the conservation of composition and non-random residue
      distribution suggests that C-domains adopt similar structures and in fact are
      structurally conserved.

PMID- 1998724
TI  - Fluorescence and kinetic properties of Ru(III) (NH3)5 modified transferrin.
AB  - Diferric transferrin was modified using aquopentaammine ruthenium(II), a reagent
      for surface-accessible uncoordinated histidines. Introduction of the cationic
      Ru(III) (NH3)3 + 5 group on the imidazole of only 5.5 of the 17 uncoordinated
      histidines enhances the rates of pyrophosphate-assisted iron removal from the N
      terminal and C-terminal binding sites by 16- and 2-fold, respectively. This
      differential effect on the kinetics of the two sites may partially explain why in
      the native protein the N-terminal site is more labile than the C-terminal site in
      acidic solutions where histidine residues become positively charged through
      protonation. The distance between the metal site and nearby uncoordinated
      histidines was estimated from fluorescence energy transfer measurements using Tb
      (III) as the donor and pentaammine ruthenium(III)-labeled imidazole of histidine
      as the acceptor chromophore. A Tsou Chen-Lu statistical analysis of the
      fluorescence quenching data suggest that two residues in each lobe of the protein
      are involved in quenching the fluorescence. By using estimates for the index of
      refraction and the quantum yield and assuming the energy transfer follows
      parallel first-order kinetics, an upper limit for the donor-acceptor distance of
      about 1.4 nm was obtained, assuming two uncoordinated histidine residues
      equidistant from the metal. His-207 and His-242 in the N-terminal lobe of
      transferrin and His-535 and His-577 in the C-terminal lobe are within this
      distance, based on information from the lactoferrin crystal structure. It is
      postulated that His-207 in the N-terminal lobe and His-535 in the C-terminal lobe
      are the uncoordinated residues that, when protonated or modified with Ru(III)
      (NH3)3 + 5, lead to accelerated loss of iron from the two binding sites of the
      protein.

PMID- 1998725
TI  - Acetylcholinesterase is orientated facing the cytoplasmic side in membranes
      derived from sarcoplasmic reticulum.
AB  - (1) Microsomal membranes from white rabbit muscle enriched in sarcoplasmic
      reticulum (SR) were used to investigate the preferential localization of
      acetylcholinesterase (AChE) in these membranes. (2) Integrity and orientation of
      the vesicles was assessed by measuring the inulin-inaccessible space of the
      vesicles and its calcium-loading capacity. (3) Treatment of the membranes with
      diisopropyl phosphorofluoridate (DFP), an irreversible inhibitor which is free
      soluble in lipid, produced an almost complete inactivation of AChE. The
      inhibition was prevented in assays performed with the non-permeant reversible
      inhibitor BW 284c51 (BW). (4) Similar results were obtained if echothiophate
      iodide (ECHO), an irreversible and poorly permeant inhibitor, instead of DFP was
      used. (5) Sedimentation profiles of enzyme solubilized with Triton X-100 from
      membranes inhibited by DFP after protection with BW showed a minor reduction in
      the relative proportion of a 4.5 S (G1) form. (6) Treatment of intact or saponin
      permeabilized membranes with concanavalin A (ConA) produced enzyme-lectin
      complexes. In both cases, most of the enzyme was recovered in the sedimented
      complexes after centrifugation of the Triton-solubilized membranes. (7)
      Incubation of intact membranes with the antibody AE1 led to the formation of
      immuno complexes. Sedimentation analyses of the molecular forms of AChE revealed
      a shift in the sedimentation coefficients, whether the antibody was added before
      or after solubilization of the enzyme. (8) These results firmly establish an
      external localization of AChE in SR, most of the protein backbone facing the
      cytoplasmic side of the membrane.

PMID- 1998726
TI  - Secondary structure of Escherichia coli glucosamine-6-phosphate deaminase from
      amino acid sequence and circular dichroism spectroscopy.
AB  - The secondary structure of the purified glucosamine-6-phosphate deaminase from
      Escherichia coli K12 was investigated by both circular dichroism (CD)
      spectroscopy and empirical prediction methods. The enzyme was obtained by
      allosteric-site affinity chromatography from an overproducing strain bearing a
      pUC18 plasmid carrying the structural gene for the enzyme. From CD analysis, 34%
      of alpha-helix, 9% of parallel beta-sheet, 11% of antiparallel beta-sheet, 15%
      turns and 35% of non-repetitive structures, were estimated. A joint prediction
      scheme, combining six prediction methods with defined rules using several
      physicochemical indices, gave the following values: alpha-helix, 37%; beta-sheet,
      22%; turns, 18% and coil, 23%. The structure predicted showed also a considerable
      degree of alternacy of alpha and beta structures; 64% of helices are amphipathic
      and 90% of beta-sheets are hydrophobic. Overall, the data suggest that deaminase
      has as dominant motif, an alpha/beta structure.

PMID- 1998727
TI  - Isolation and characterization of 5'-nucleotidase of a human pancreatic tumor
      cell line.
AB  - 5'-Nucleotidase of a human pancreatic tumor cell line (PaTu II) has been purified
      to homogeneity after extraction with detergent followed by two affinity
      chromatographic steps. Sodium dodecyl sulphate polyacrylamide gel electrophoresis
      of purified 5'-nucleotidase revealed a single polypeptide band of 67 kDa. The
      Western blotted enzyme can be overlaid with concanavalin A proving its
      glycoprotein nature. After treatment with endoglycosidase F the deglycosylated 5'
      nucleotidase exhibits an apparent molecular mass of 58 kDa. The kinetic
      properties of the solubilized enzyme have been determined (Km (AMP) of 4.0
      microM; Vmax (AMP) = 8.6 muMOL/min.mg). Adenosine 5'-[alpha,beta
      methylene]diphosphate is a competitive inhibitor of 5'-nucleotidase, whereas
      concanavalin A inhibits the enzymatic activity in a non-competitive manner.
      Polyclonal antibodies against purified 5'-nucleotidase of PaTu II have been
      produced which inhibit its enzymatic activity. Polyclonal antibodies raised
      against the enzyme purified from rat liver or bull seminal plasma also recognize
      5'-nucleotidase of PaTu II cells, whereas polyclonal and monoclonal antibodies
      against the enzyme derived from chicken gizzard show no cross-reactivity. 5'
      Nucleotidase appears to be concentrated in the plasma membrane of PaTu II cells
      as judged by cell fractionation and indirect immunofluorescence studies.

PMID- 1998728
TI  - Possible regulation of the in vitro assembly of bovine brain tubulin by the
      bovine thioredoxin system.
AB  - Microtubule assembly in vitro and in vivo is highly sensitive to a variety of
      sulfhydryl-reactive reagents, raising the question of the possible existence of a
      physiological sulfhydryl-mediated system for regulating microtubule assembly.
      However, the specific reagents which have previously been used to inhibit
      microtubule assembly in vitro are either nonphysiological or, if physiological,
      effective only at concentrations much higher than their physiological ones.
      Because of reports of association in vivo between microtubules and the sulfhydryl
      reactive proteins thioredoxin and thioredoxin reductase, we decided to examine
      the interaction in vitro between microtubules and the thioredoxin system,
      comprising thioredoxin, thioredoxin reductase and NADPH. At pH 6.8, both the
      mammalian and the Escherichia coli thioredoxin systems inhibited microtubule
      assembly by 4-35% (19 +/- 9%) by reducing one intra-subunit disulfide bond in the
      tubulin dimer. The thioredoxin-reducible disulfide of the tubulin dimer remains
      protected from thioredoxin in the assembled microtubules. Thioredoxin or
      thioredoxin reductase alone, or together in the absence of NADPH, were incapable
      of either reducing tubulin or inhibiting microtubule assembly. Microtubules
      formed from reduced tubulin were found to be stable and morphologically identical
      to those obtained from native tubulin dimers. Since the components of the
      thioredoxin system were used at concentrations similar to their physiological
      ones, our results suggest a potential role of the thioredoxin system in
      regulation of microtubule assembly in vivo.

PMID- 1998729
TI  - Beta oxidation of fatty acids.

PMID- 1998730
TI  - Kinetic advantage of the interaction between the fatty acid beta-oxidation
      enzymes and the complexes of the respiratory chain.
AB  - Respiration-linked oxidation of 3-hydroxybutyryl-CoA, crotonyl-CoA and saturated
      fatty acyl (C4, C8 and C14)-CoA esters was studied in different mitochondrial
      preparations. Oxidation of acyl-CoA esters was poor in intact mitochondria;
      however, it was significant, as well as, NAD+ and CoA-dependent in gently and in
      vigorously sonicated mitochondria. The respiration-linked oxidation of crotonyl
      CoA and 3-hydroxybutyryl-CoA proceeded at much higher rates (over 700%) in gently
      disrupted mitochondria than in completely disrupted mitochondria. The redox dye
      linked oxidation of crotonyl-CoA (with inhibited respiratory chain) was also
      higher in gently disrupted mitochondria (149%) than in disrupted ones. During the
      respiration-linked oxidation of 3-hydroxybutyryl-CoA the steady-state NADH
      concentrations in the reaction chamber were determined, and found to be 8 microM
      in gently sonicated and 15 microM in completely sonicated mitochondria in spite
      of the observation that the gently sonicated mitochondria oxidized the 3
      hydroxybutyryl-CoA much faster than the completely sonicated mitochondria. The
      NAD(+)-dependence of 3-hydroxybutyryl-CoA oxidation showed that a much smaller
      NAD+ concentration was enough to half-saturate the reaction in gently disrupted
      mitochondria than in completely disrupted ones. Thus, these observations indicate
      the positive kinetic consequence of organization of beta-oxidation enzymes in
      situ. Respiration-linked oxidation of butyryl-, octanoyl- and palmitoyl-CoA was
      also studied and these CoA intermediates were oxidized at approx. 50% of the rate
      of crotonyl- and 3-hydroxybutyryl-CoA in the gently disrupted mitochondria. In
      vigorously disrupted mitochondria the oxidation rate of these saturated acyl-CoA
      intermediates was hardly detectable indicating that the connection between the
      acyl-CoA dehydrogenase and the respiratory chain had been disrupted.

PMID- 1998731
TI  - Lung calcium-dependent phospholipid-binding proteins: structure and function.
AB  - Distinct peptide maps of two rabbit lung Ca2(+)-dependent phospholipid-binding
      proteins (PLBPs), 36,000 and 33,000, were generated by cyanogen bromide (CNBr)
      cleavage, trypsin or Staphylococcus aureus V8 proteinase digestion. The amino
      acid sequence of a CNBr-cleaved peptide of the 36,000 PLBP was aligned to the
      amino terminus of human lipocortin I with more than 77% identity, but had no
      identity with the known amino terminal sequence of other known annexins. Partial
      amino acid sequence of a 33,000 PLBP peptide demonstrated a close (56%)
      relationship to endonexin II, human placental anticoagulant protein, and porcine
      intestine protein II, but shared only 32% identity with lipocortin I, 30% with
      lipocortin II. Antiserum generated against purified 36,000 PLBP reacted strongly
      with the 33,000 PLBP, but did not react with any other rabbit lung cytosolic
      proteins. Both PLBPs inhibited the phospholipase A2 reaction when dioleoyl
      phosphatidylcholine and phosphatidylglycerol vesicles or monolayers were used as
      substrates. In the vesicle assay, the phospholipase A2 reaction was inhibited at
      lower substrate phospholipid concentrations but not at nearly saturating
      substrate concentrations. In the monolayer assay, the phospholipid-binding
      proteins did not inhibit phospholipase A2 at a low phospholipid surface
      concentration of 3.8.10(-3) molecules/A2, but they did at higher surface
      concentrations between 1.1 x 10(-2) and 3.8 x 10(-2) molecules/A2. The inhibition
      of phospholipase A2 by rabbit lung phospholipid-binding proteins is most likely
      due to the prevention of penetration by phospholipase A2 into the interface, a
      requirement for the enzyme to act on the substrate.

PMID- 1998732
TI  - Sexual dimorphism in the preferential secretion of unsaturated
      lysophosphatidylcholine by rat hepatocytes but no secretion by sheep hepatocytes.
AB  - (1) Rat and ovine hepatocytes were incubated in monolayer culture with various
      fatty acids to determine their effects on the composition of the
      lysophosphatidylcholine that was secreted. (2) No lysophosphatidylcholine was
      detected in the medium from the ovine hepatocytes even though these cells were
      hormonally responsive and they secreted phosphatidylcholine and triacylglycerol
      in very-low-density lipoprotein. (3) Lysophosphatidylcholine was readily detected
      in the incubation medium of rat hepatocytes. The predominant fatty acids in this
      lipid were unsaturated. Stearate and arachidonate contributed 15 and 34%, and 24
      and 26% of the total fatty acids when hepatocytes from male and female rats were
      used, respectively. The relative proportions of stearate and arachidonate in the
      phosphatidylcholine secreted from the hepatocytes were 20 and 14%, and 28 and 21%
      for the males and females, respectively. The equivalent values for stearate and
      arachidonate for phosphatidylcholine in the hepatocytes were 18 and 17% and 33
      and 22% for male and female rats. These results provide further indications of
      sex differences in hepatic phospholipid metabolism and extend this to the
      secretion of phosphatidylcholine and lysophosphatidylcholine. (4) The addition of
      1 mM stearate to the incubation medium did not significantly decrease the
      proportion of arachidonate in the lysophosphatidylcholine obtained from the
      hepatocytes of the male rats. However, the relative proportion of arachidonate
      was decreased in incubations that contained 1 mM oleate or linoleate. (5) The
      results provide evidence that the preferential secretion of unsaturated
      lysophosphatidylcholine by the liver may provide a system for transporting
      unsaturated fatty acids and choline to other organs in non-ruminant animals.
      However, this mechanism may not operate for ruminants.

PMID- 1998733
TI  - A sensitive assay of lysogangliosides using high-performance liquid
      chromatography.
AB  - Lysogangliosides, LGM1, LGM2 and LGM3, each carrying a single sphingoid base
      (i.e., C18:1, C18:0, C20:1, C20:0), were prepared and a sensitive assay method of
      these lipids using HPLC was developed. The method involves fluorescence
      derivatization of the free amino group of the molecule with o-phthalaldehyde,
      separation of the molecular species of each lysoganglioside using reversed-phase
      HPLC and assay on the basis of a known amount of one of the lysogangliosides, as
      the internal standard. Using this method, lysoganglioside can be accurately
      assayed in the range of 5-1000 pmol. For assay of the lipid in the tissue, crude
      isolation procedures including extraction of lipids, Folch's partition and DEAE
      Sepharose and AG 1-X2 column chromatographies were required before the
      fluorescence derivatization. In the normal human and the bovine cerebral cortex,
      0.4-2.0 pmol/mg protein of LGM1 containing C18:1 and C20:1 sphingosine residues
      were detected. In the frontal cortex from a patient with Sandhoff disease, an
      abnormal accumulation (55-78 pmol/mg protein) of LGM2 was noted. Among various
      molecular species, LGM2 containing C18:1 was the most abundant.

PMID- 1998734
TI  - Omega-oxidation of fatty acids studied in isolated liver cells.
AB  - The omega- and beta-oxidation of medium- and long-chain fatty acids (C10-C18)
      were studied in hepatocytes from fasted, fed and clofibrate-fed rats. The omega
      oxidation systems were most active with lauric acid (12:0) and decanoic acid
      (10:0) as substrates and there was decreasing activity with chain lengths from 14
      to 18 carbon atoms. In fed rats no omega-oxidation of fatty acids was detected
      unless the mitochondrial beta-oxidation was inhibited. In fasted rats the omega
      oxidation was less than 2% and preincubation with (+)-decanoylcarnitine increased
      the omega-oxidation to 15% of the total fatty acid oxidation. Clofibrate feeding
      did not increase the omega-oxidation in isolated hepatocytes. Inhibition of the
      alcohol dehydrogenase with 4-methylpyrazole inhibited both the oxidation of omega
      hydroxylated fatty acid and the initial hydroxylation of lauric acid to
      dicarboxylic acid, suggesting the importance of the alcohol dehydrogenase in the
      omega-oxidation of fatty acids. 95% of the dicarboxylic acids and 80% of the
      hydroxy-fatty acids were excreted from the cells in the incubations with decanoic
      acid (10:0). No chain-shortened dicarboxylic acids were detected with [1
      14C]decanoic- or [1-14C]lauric acid as substrate, while small amounts C10 and C12
      dicarboxylic acids were observed in incubations with [1-14C]myristic acid (14:0).

PMID- 1998735
TI  - Metabolism of oxidized linoleic acid: characterization of 13
      hydroxyoctadecadienoic acid dehydrogenase activity from rat colonic tissue.
AB  - An oxidized derivative of linoleic acid, 13-hydroxyoctadecadienoic acid (13
      HODE), is dehydrogenated by an NAD+ dependent dehydrogenase present in rat colon
      mucosa. The product of the reaction is the 2,4-dienone, 13-oxooctadecadienoic
      acid. Enzyme activity was determined by HPLC analysis of incubation mixtures as
      well as by measuring the increase in absorbance at 285 nm, which represents
      formation of the 2,4-dienone chromophore. Characteristics of the reaction with
      respect to protein concentration, time of incubation and substrate dependence
      were investigated. Several inhibitors of known dehydrogenases had no effect on
      the 13-HODE dehydrogenase. These include, ethanol, indomethacin, 6-methyl-17
      hydroxyprogesterone acetate, 4-(diethylamino)-benzaldehyde, and aspirin. The
      enzyme was mildly inhibited by pyrazole, 4-methylpyrazole and ibuprofen.
      Disulfiram was found to be a potent inhibitor of enzyme activity with an IC50 of
      200 microM. Inhibitor specificity, and other characteristics of the reaction
      suggest the enzyme is neither alcohol dehydrogenase, diol dehydrogenase, nor a
      prostaglandin dehydrogenase. It is possible this enzyme plays an important role
      in the response of the colonic mucosa to the mitogenic effect of oxidized fatty
      acids.

PMID- 1998736
TI  - Spectroscopic detection of lipid peroxidation products and structural changes in
      a sphingomyelin model system.
AB  - The peroxidation induced by tert-butyl hydroperoxide in sphingomyelin from bovine
      brain was investigated in detail. The lipid peroxidation products resulting from
      oxidation of lipid acyl chains were detected, identified and characterized by
      optical absorption. Fourier transform infrared, fluorescence and NMR
      spectroscopies. The extent of hydrocarbon chain degradation in vitro was
      quantified by measuring the relative change in absorbance of the peak at 241 nm
      characteristic of conjugated double bond or diene absorption band. FTIR data
      revealed that the lipid peroxidation of sphingomyelin disrupted the acyl chain
      and head group regions resulting in derangement of the ordered membrane.

PMID- 1998737
TI  - Interaction of a high-affinity heparin subfraction with low-density lipoprotein
      stimulates cholesteryl ester accumulation in mouse macrophages.
AB  - A high-affinity heparin subfraction accounting for 8% of whole heparin from
      bovine lung was isolated by low-density lipoprotein (LDL)-affinity
      chromatography. When compared to whole heparin, the high-affinity subfraction was
      relatively higher in molecular weight (11,000 vs. 17,000) and contained more
      iduronyl sulfate as hexuronic acid (76% vs. 86%), N-sulfate ester (0.75 vs. 0.96
      mol/mol hexosamine), and O-sulfate ester (1.51 vs. 1.68 mol/mol hexosamine).
      Although both heparin preparations formed insoluble complexes with LDL
      quantitatively in the presence of 30 mM Ca2+, the concentrations of NaCl required
      for 50% reduction in maximal insoluble complex formation was markedly higher with
      high-affinity subfraction (0.55 M vs. 0.04 M). When compared to complex of 125I
      LDL and whole heparin (H-125I-LDL), complex of 125I-LDL and high-affinity heparin
      subfraction (HAH-125I-LDL) produced marked increase in the degradation of
      lipoproteins by macrophages (7-fold vs. 1.4-fold over native LDL, after 5 h
      incubation) as well as cellular cholesteryl ester synthesis (16.7-fold vs. 2.2
      fold over native LDL, after 18 h incubation) and content (36-fold vs. 2.7-fold
      over native LDL, after 48 h incubation). After a 5 h incubation, macrophages
      accumulated 2.3-fold more cell-associated radioactivity from HAH-125I-LDL complex
      than from [125I]acetyl-LDL. While unlabeled HAH-LDL complex produced a dose
      dependent inhibition of the degradation of labeled complex, native unlabeled LDL
      did not elicit any effect even at a 20-fold excess concentration. Unlabeled
      particulate LDL aggregate competed for 33% of degradation of labeled complex;
      however, cytochalasin D, known inhibitor of phagocytosis, did not effectively
      inhibit the degradation of labeled complex. Unlabeled acetyl-LDL produced a
      partial (33%) inhibition of the degradation of labeled complex. These results
      indicate that (1) the interaction of high-affinity heparin subfraction with LDL
      leads to scavenger receptor mediated endocytosis of the lipoprotein, and
      stimulation of cholesteryl ester synthesis and accumulation in the macrophages;
      and (2) with respect to macrophage recognition and uptake, HAH-LDL complex was
      similar but not identical to acetyl-LDL. These observations may have implications
      for atherogenesis, because both mast cells and endothelial cells can synthesize
      heparin in the arterial wall.

PMID- 1998738
TI  - Smoking alters thromboxane metabolism in man.
AB  - Chronic smoking is a major risk factor of atherosclerosis and coronary heart
      disease. The measurement of three major thromboxane A2 metabolites, 11
      dehydrothromboxane B2, 2,3-dinorthromboxane B2 and thromboxane B2, in the urines
      of 13 apparently healthy smokers (average 39 years, range 27-56 years) showed
      significantly elevated excretion rates for all thromboxane A2 metabolites as
      compared to 10 apparently healthy age-matched non-smokers (average 37 years,
      range 26-56 years). Importantly, characteristic alterations in the thromboxane A2
      metabolite pattern were found in the urines of smokers. The contribution of 2,3
      dinorthromboxane B2 to total measured excretion of thromboxane A2 metabolites was
      59.2% in smokers (404.0 +/- 53.0 pg/mg creatinine) versus 19.4% in non-smokers
      (85.2 +/- 8.3 pg/mg creatinine), that of 11-dehydrothromboxane B2 35.7% in
      smokers (673.2 +/- 88.9 pg/mg creatinine) as compared to 75.5% in non-smokers
      (332.6 +/- 30.9 pg/mg creatinine). The contribution of thromboxane B2 (57.5 +/-
      7.7 pg/mg creatinine in smokers versus 21.9 +/- 1.5 pg/mg creatinine in non
      smokers) was similar at 5.1%. The excretion of cotinine, the major urinary
      metabolite of nicotine that correlates well with the reported daily cigarette
      consumption (r = 0.97, P less than 0.0001), showed a good correlation to
      thromboxane A2 metabolite excretion (2,3-dinorthromboxane B2: r = 0.92, P less
      than 0.0001; 11-dehydrothromboxane B2; r = 0.87, P less than 0.0001).

PMID- 1998739
TI  - In vivo clearance of low-density lipoproteins and beta-very-low-density
      lipoproteins in normal and hypercholesterolemic White Carneau pigeons.
AB  - Low-density lipoproteins (hLDL) and beta-migrating-very-low-density lipoproteins
      (beta-VLDL) were isolated from the plasma of cholesterol-fed White Carneau (WC)
      pigeons and low-density lipoproteins (nLDL) were isolated from the plasma of
      grain-fed WC pigeons. The lipoproteins were radiolabeled with 125I or 131I and
      injected into normocholesterolemic or hypercholesterolemic WC pigeons to
      determine their rate of clearance from the plasma. The fractional catabolic rate
      (FCR) of nLDL and hLDL in normocholesterolemic pigeons averaged 0.202 and 0.206
      pools/h.respectively. beta-VLDL was cleared at a significantly slower rate of
      0.155 pools/h. The FCR of the same lipoproteins injected into
      hypercholesterolemic pigeons was reduced by 17% for nLDL, 50% for hLDL and 57%
      for beta-VLDL, indicating that the effect of hypercholesterolemia on clearance in
      vivo was different for the three lipoproteins. The FCR of reductively methylated
      pigeon LDL (MeLDL), which gives a measure of receptor-independent clearance of
      LDL, was shown previously to be 0.037 pools/h. These studies suggest therefore
      that LDL and beta-VLDL are cleared from the plasma of normocholesterolemic and
      hypercholesterolemic pigeons at a rate substantially greater than that predicted
      for non-specific processes. Despite the reduction in the clearance rate of hLDL
      and beta-VLDL due to cholesterol feeding, the absolute amount of cholesterol that
      was cleared from the plasma by these lipoproteins was increased from approx. 200
      mg/kg body weight per day in the normocholesterolemic pigeons to greater than
      1000 mg/kg body weight per day in the hypercholesterolemic pigeons. This is due
      principally to the enrichment in cholesterol relative to protein of the
      lipoproteins isolated from cholesterol-fed pigeons and the failure of
      hypercholesterolemia to completely inhibit receptor-dependent clearance of LDL
      and beta-VLDL. The lower rate of clearance of beta-VLDL relative to LDL is in
      marked contrast to mammalian beta-VLDL, which is cleared much faster than LDL,
      but is consistent with the lack of apo E on pigeon lipoproteins. Apo E is the
      apoprotein that is thought to be responsible for the rapid clearance of beta-VLDL
      in normocholesterolemic mammals. The low rate of beta-VLDL clearance in pigeons
      also suggests that pigeons lack an apolipoprotein that function like mammalian
      apo E.

PMID- 1998741
TI  - Effects of apolipoprotein structure on the kinetics of apolipoprotein transfer
      between phospholipid vesicles.
AB  - The kinetics and mechanism of transfer of 14C-labeled human apolipoproteins A-I,
      A-II and C-III1 between small unilamellar vesicles (SUV) have been investigated.
      Ion exchange chromatography was used for rapid separation of negatively charged
      egg phosphatidylcholine (PC)/dicetyl phosphate donor SUV containing bound 14C
      labeled apoprotein from neutral egg PC acceptor SUV present in 10-fold molar
      excess. The transfer kinetics of these apolipoproteins at 37 degrees C are
      consistent with the existence of fast, slow and apparently 'nontransferrable'
      pools of SUV-associated lipoprotein: the transfers from these pools occur on
      timescales of seconds (or less), minutes/hours and days/weeks, respectively. For
      donor SUV containing about 15 apoprotein molecules per vesicle and at a donor SUV
      concentration of 0.15 mg phospholipid/ml incubation mixture, the sizes of the
      fast kinetic pools for apolipoproteins A-I, A-II and C-III1 associated with donor
      SUV are 2, 10 and 11%, respectively. The sizes of the slow kinetic pools for
      these apolipoproteins are 16, 71 and 50%, respectively. The transfer of the
      various apolipoproteins from the slow kinetic pool follows first order kinetics
      and the half-time (t1/2) values are in the order: apo C-III1 less than apo A-I.
      Increasing the number of apoprotein molecules per donor SUV enlarges the size of
      the fast pool and increases the t1/2 of slow transfer. The differences in the
      kinetics of apolipoprotein transfer between SUV are consequences of the
      variations in the primary and secondary structures of the apolipoprotein
      molecules. The slow transfer of apoprotein molecules is mediated by collisions
      between donor and acceptor SUV; the rate is dependent on the apoprotein molecular
      weight with larger molecules transferring more slowly from donor SUV containing
      the same lipid/protein molar ratio. The hydrophobicity of the apoprotein molecule
      is also significant with less hydrophobic molecules transferring more rapidly.
      Further understanding of the differences in the kinetics of transfer of these
      apolipoproteins will require more knowledge of their secondary and tertiary
      structures.

PMID- 1998740
TI  - Behaviour of phospholipase modified-HDL towards cultured hepatocytes. II.
      Increased cell cholesterol storage and bile acid synthesis.
AB  - Human total HDL (hydrated density 1.070-1.210), HDL2 (1.070-1.125), HDL3 (1.125
      1.210) or HDL separated by heparin affinity chromatography were treated with or
      without purified phospholipase A2 from Crotalus adamanteus. Control and treated
      HDL were reisolated and were then incubated with cultured hepatocytes. 1. Mass
      measurements evidenced a time-dependent cholesterol enrichment in hepatocytes
      cultured in the absence of lipoproteins. Addition of HDL2 still enhanced by 25%
      the cell cholesterol content and down-regulated endogenous sterol synthesis in
      similar proportions. Conversely, HDL3 slightly decreased the amount of free
      cholesterol in hepatocytes (-12%). 2. Incubations with phospholipase A2-treated
      HDL resulted in a 35%-50% increase of both the cellular cholesterol
      esterification and the cholesterylester accumulation, when compared to cells
      cultured in the presence of control-HDL. This effect was observed with HDL2, HDL3
      and combining the data with all subfractions. 3. Cultured hepatocytes secreted
      cholic and beta-muricholic acids as major bile acids and HDL2 showed a tendency
      to stimulate their secretion. Phospholipase treatment of HDL again induced an
      increased production by hepatocytes of those two bile acids. Thus, whereas HDL2
      and HDL3 display different behaviours with respect to cell cholesterol content,
      neosynthesis and bile acid secretion, their modifications by phospholipases
      always orientate the cell sterol metabolism in the same direction: increased
      cholesterylester accumulation and bile acid production.

PMID- 1998742
TI  - Removal of cholesteryl ester from hepatic reticuloendothelial cells in vivo is
      not enhanced by plasma cholesteryl ester transfer protein.
AB  - The putative role of cholesteryl ester transfer protein (CETP) in the removal of
      cholesteryl ester from hepatic reticuloendothelial cells in vivo was studied in
      hamsters. The parameter tested was retention of [3H]cholesteryl linoleyl ether
      ([3H]CLE), a nonhydrolysable analog of cholesteryl ester, in the liver after
      injection of [3H]CLE labeled acetylated LDL, which is targetted to
      nonparenchymatous littoral cells. In hamsters fed laboratory chow, plasma
      cholesteryl ester transfer activity (CETA) was 10.6 +/- 0.9 units and the
      retention of [3H]CLE in the liver 28 days after injection was 86% of the 4 h
      value. It was about 55% in rats fed the same diet, in which CETA was not
      detectable. When the diet was supplemented with 2% cholesterol and 15% margarine,
      CETA activity in hamsters increased 2-fold, yet no change in retention of [3H]CLE
      in liver was seen after 28 days. In rats, the retention of [3H]CLE in the liver
      was also not changed by the dietary fat supplementation. These results do not
      support the role of CETP in vivo in removal of cholesteryl ester from intact
      reticuloendothelial cells.

PMID- 1998743
TI  - Defective plasma clearance of chylomicron-like lipid emulsions in Watanabe
      heritable hyperlipidemic rabbits.
AB  - Human patients with familial hypercholesterolemia (FH) and Watanabe heritable
      hyperlipidemic rabbits (WHHL), while lacking normal receptors recognizing low
      density lipoproteins (LDL), are said to have normal clearance of chylomicrons. In
      the present study, emulsions with a similar lipid composition to chylomicrons
      were injected intravenously in homozygous WHHL rabbits and normal control rabbits
      fed diet with low or high cholesterol. Radioactive labels tracing emulsion
      triolein and cholesteryl oleate were both removed rapidly from the bloodstream,
      with the removal rate of triolein always faster than that of cholesteryl oleate.
      This pattern was similar to the clearance of normal chylomicrons in rabbits or
      rats, and was consistent with the formation of remnant lipoproteins after
      hydrolysis of emulsion triolein by lipoprotein lipase, followed by hepatic uptake
      of the remnants. The removal of cholesteryl oleate was significantly slower in
      WHHL rabbits than in normal controls, suggesting that the absence of LDL receptor
      function led to impaired remnant clearance. Measured in post-heparin plasma, the
      activity of lipoprotein lipase was decreased in WHHL rabbits, but this was not
      associated with clear evidence of defective lipolysis of emulsion triolein.
      Apolipoprotein E did not appear to be deficient in WHHL rabbits. Plasma devoid of
      lipoproteins less than 1.006 g/ml from WHHL and normal control rabbits
      transferred similar amounts of apolipoprotein E to chylomicron-like emulsions
      after incubation. Impaired clearance of chylomicron remnants possibly contributes
      to the hypertriglyceridemia of WHHL rabbits and to accelerated atherogenesis when
      the function of LDL receptors is defective.

PMID- 1998744
TI  - Effects of hyperthyroidism on synthesis, secretion and metabolism of the VLDL
      apoproteins by the perfused rat liver.
AB  - Livers from fed male Sprague-Dawley rats, made hyperthyroid by treatment with
      triiodothyronine (T3), were isolated and perfused in vitro. T3 (9.6
      micrograms/day) was administered by osmotic minipump implanted intraperitoneally.
      Treatment with T3 for either 7 or 28 days reduced hepatic output of very-low
      density lipoprotein (VLDL) and net synthesis of total associated apoproteins.
      After 7 days treatment, incorporation of [4,5-3H]leucine by livers from
      hyperthyroid rats into VLDL apo E was reduced while incorporation into apo B100,
      apo B48, and apo C's did not differ from euthyroid controls. The depressed
      incorporation of radioactivity into total VLDL protein was accounted for almost
      entirely on the basis of apo E. Incorporation of leucine into the total
      lipoprotein apo E isolated in the d less than 1.210 was also diminished by the
      hyperthyroid state, while that into apo B100, apo B48, and apo C in the total
      perfusate lipoprotein was similar to that of the euthyroid, as was found for the
      VLDL. Increased amounts of radioactive apo B100 and apo B48, however, were
      detected in the HDL fraction isolated from the medium perfusing livers from
      hyperthyroid rats. Hepatic uptake of VLDL protein and lipid was similar in
      euthyroid and hyperthyroid rats. Reduction of VLDL lipid and protein in the
      medium perfusing livers from T3-treated rats, therefore reflects hormonal action
      on synthesis and secretion, rather than uptake. Since the availability of apo B
      is thought to be required for secretion of VLDL, our observation suggests that
      synthesis of apo B is not depressed by treatment with T3 and that apoprotein
      synthesis is not a significant factor in the decreased output of VLDL by the
      liver, but that, as reported earlier, the lower output is a consequence of
      decreased synthesis of TG, the result of a diminished supply of hepatic glycero-3
      phosphate in the hyperthyroid. The diminished amount of VLDL protein appears to
      be accounted for by the decreased quantity of apo E associated with a smaller
      VLDL particle secreted by livers from T3-treated rats.

PMID- 1998745
TI  - Role of the side chain of lanosterol in substrate recognition and catalytic
      activity of lanosterol 14 alpha-demethylase (cytochrome P-450 (14DM)) of yeast.
AB  - The 14 alpha-demethylation of 24,25-dihydrolanosterol (DHL) derivatives having
      trimmed side chains, 27-nor-DHL, 26,27-dinor-DHL, 25,26,27-trinor-DHL,
      24,25,26,27-tetranor-DHL, 23,24,25,26,27-pentanor-DHL and 22,23,24,25,26,27
      hexanor-DHL, was studied with the reconstituted lanosterol 14 alpha-demethylase
      system consisting of cytochrome P-450(14DM) and NADPH-cytochrome P-450 reductase
      both purified from yeast microsomes. The demethylase catalyzed the 14 alpha
      demethylation of the derivatives having the side chains longer than tetranor but
      the activities for the trinor- and tetranor-derivatives were lower. Kinetic
      analysis indicated that affinity of the trinor-derivative for the demethylase was
      considerably higher than that of DHL. The affinities of the 27-nor- and dinor
      derivatives were increased by this order and were the intermediates of DHL and
      the trinor derivative. On the other hand, Vmax values of the demethylase for the
      DHL derivatives were decreased depending on their side-chain lengths, and the
      substrate-dependent reduction rate of cytochrome P-450(14DM) was also decreased
      in the same manner. Based on these observations, it was concluded that
      interaction of the side chain of lanosterol especially C-25, 26 and 27 with the
      substrate site of lanosterol 14 alpha-demethylase was necessary for enhancing the
      catalytic activity of the enzyme. However, this interaction was considered not to
      be essential for substrate binding.

PMID- 1998746
TI  - Effect of sterol side-chain structure on the feed-back control of sterol
      biosynthesis in yeast.
AB  - We measured the incorporation of radiolabeled methionine and acetate into the
      sterol component of G204, a Saccharomyces cerevisiae mutant strain which is
      partially heme competent. By comparing the amount of label incorporated into the
      sterol pool of a control culture, to which no exogenous sterol was added, with a
      culture which had various sterols added to the growth medium, we were able to
      determine the specific structural features of ergosterol which facilitate its
      ability to restrict the sterol biosynthetic pathway. These experiments
      demonstrate that sterols which contain both a C22 unsaturation and a C24 methyl
      group are capable of reducing sterol biosynthesis by approx. 50%, regardless of B
      ring structure. We examined the regulatory properties of various oxysterols;
      24,25-epoxylanosterol reduced endogenous biosynthesis by 49%, whereas all
      cholesterol derivatives tested, including 25-hydroxycholesterol, had little
      effect. A new procedure for the synthesis of ergosterol peroxides is also
      described.

PMID- 1998747
TI  - Localization of enzymes involved in glycero-ether bond formation in rat liver.
AB  - Studies on the localization of alkyldihydroxyacetone-phosphate synthase in rat
      liver are described. Less than 5% of the total activity was found in the
      cytosolic fraction, suggesting that the enzyme is membrane-bound. The ratio of
      the enzymatic (specific) activity over that of dihydroxyacetone-phosphate
      acyltransferase, a peroxisomal enzyme, is 10-fold higher in the microsomal
      fraction, when compared to the peroxisomal fraction. Studying the distribution of
      the enzyme in a linear density gradient, two activity peaks were found in the
      peroxisomal and the microsomal fraction indicating a bimodal localization of
      alkyldihydroxyacetone-phosphate synthase. Rabert et al. (Rabert, U., Volkl, A.
      and Debuch, H. (1986) Biol. Chem. Hoppe-Seyler 367, 215-222) have presented
      evidence that the activity in the microsomal fraction was mainly caused by a
      different enzyme that preferentially converted acyldihydroxyacetone to
      alkyldihydroxyacetone. We also found a radioactive product, different from
      alkyldihydroxyacetone-phosphate, upon incubation of microsomal protein in the
      presence of [14C]hexadecanol. However, it was shown that this product was formed
      independently of the presence of acyldihydroxyacetone. The product yielded
      [14C]hexadecanol upon alkaline hydrolysis, clearly showing that it did not
      contain an ether-bond. Upon incubation of microsomal protein with [14C]palmitic
      acid and hexadecanol the product was also observed and its chromatographic
      behaviour resembled that of a synthetically prepared palmitoyl ester of
      hexadecanol. From these data it was concluded that the product formed is most
      likely a wax and that the enzyme responsible for this conversion is clearly
      different from the alkyldihydroxyacetone-phosphate synthase. The implication is
      that acyldihydroxyacetone-phosphate cannot be replaced by acyldihydroxyacetone in
      the process of glycero-ether bond formation.

PMID- 1998748
TI  - Effects of probucol on lipid metabolism and secretion in long-term cultures of
      adult rat hepatocytes.
AB  - To study the effects of probucol on hepatic lipid metabolism, we used adult rat
      hepatocytes cultured on a feeder layer of 3T3 cells lethally treated with
      mitomycin C. These cultures synthesize and secrete for at least 2 weeks various
      lipids from [14C]acetate and [14C]oleate precursors. Treatment with 20
      micrograms/ml of probucol for 7 and 14 days decreased the secretion of various
      radiolabeled lipid species to the culture medium and produced an intracytoplasmic
      accumulation of triacylglycerol droplets. The lipids whose secretion was most
      decreased were free and esterified cholesterol (50-70% reduction). Secretion of
      triacylglycerols and phospholipids was also reduced but to a lower extent.
      Intracytoplasmic triacylglycerols accumulated and the activity of glycerol
      phosphate dehydrogenase, a marker enzyme of glycerolipid synthesis, also
      increased (35-56%). The total incorporation of both radioactive precursors into
      free and esterified cholesterol and phospholipids was reduced 20-60%. Our data
      show that 2-week treatment of 3T3-hepatocyte cultures with pharmacological
      concentrations of probucol reduces significantly lipid secretion and suggest that
      at least part of the in vivo hypolipidemic effect of probucol could be attributed
      to a decrease in the secretion of lipids (i.e., lipoproteins) by hepatocytes.

PMID- 1998749
TI  - Synthesis, structural identification and biological activity of 11,12
      dihydroxyeicosatetraenoic acids formed in human platelets.
AB  - An enantiospecific route for the synthesis of 11,12-dihydroxyeicosatetraenoic
      acids was developed and used to synthesize 11,12-dihydroxy-5(Z),7(E),9(E),14(Z)
      eicosatetraenoic acids. The 11,12-DHETEs were synthesized with the
      stereochemistry of the hydroxyl group being 11(R),12(S) and 11(S),12(S). The
      synthetic compounds were used to elucidate the structure of 11,12-DHETEs formed
      in human platelets by comparison of the chromatographic retention time in HPLC
      and GC as well as their ion fragmentation pattern in GC-MS. The major 11,12-DHETE
      formed in human platelets was found to be identical with 11(R),12(S)-dihydroxy
      5(Z),7(E),9(E),14(Z)-eicosatetraenoic acid. Two more compounds were tentatively
      identified as 11(S),12(S)-dihydroxy-5(Z),7(E),9(E),14(Z)-eicosatetraenoic acid
      and 11,12-dihydroxy-5(E),7(E),9(E),14(Z)-eicosatetraenoic acid. Furthermore, the
      11(S),12(S)-dihydroxy-5(Z),7(E),9(E),14(Z)-eicosatetraenoic acid was found to
      possess biological activity on neutrophil functional responses. However, the
      major compound, 11(R),12(S)-dihydroxy-5(Z),7(E),9(E),14(Z)-eicosatetraenoic acid,
      formed in platelets lacks biological activity in the test systems used. The
      present data further support that 11,12-dihydroxy-eicosatetraenoic acids are
      formed in human platelets via a leukotriene like mechanism presumably by the 12
      lipoxygenase. Furthermore, the biological effects of one of the compounds showed
      a unique activity profile compared to other lipoxygenase products.

PMID- 1998750
TI  - Characterization of a new phosphonocerebroside, N-methyl-2
      aminoethylphosphonylglucosylceramide, from the antarctic krill, Euphausia
      superba.
AB  - A novel phosphonglycosphingolipid was purified from the whole tissue of the
      antarctic krill, Euphausia superba by successive column chromatography on DEAE-
      and QAE-Sephadex and silicic acid (Iatrobeads). The structure was elucidated by
      means of IR, FAB-MS, 1H-NMR, GC and GC-MS analyses of the water-soluble products
      after complete and partial acid hydrolysis, and methylation analysis of a product
      of hydrogen fluoride degradation; it was identified to be a phosphonocerebroside,
      6'-O-(N-methyl-2-aminoethylphosphonyl)Glcp beta 1----1ceramide. The ceramide
      moiety was composed of tetradecasphingenine and octadecasphingatriene as the main
      sphingoids, and monounsaturated C22- and C24-acids and their 2-hydroxy homologues
      as the major fatty acids.

PMID- 1998751
TI  - Interactions between model triacylglycerol-rich lipoproteins and high-density
      lipoproteins in rat, rabbit and man.
AB  - There are inverse relationships between HDL cholesterol and plasma
      triacylglycerol concentrations in normal and in hypertriglyceridemic individuals.
      To investigate the interactions between triacylglycerol-rich lipid particles and
      HDL, a lipid emulsion model of the triacylglycerol-rich lipoproteins was
      prepared. When emulsion particles were incubated with rat high-density
      lipoproteins (HDL) in the presence of lipid transfer activity (d greater than
      1.21 g/ml fractions) from rabbit or human plasma there was a rapid bi-directional
      exchange of cholesteryl oleate (CO) and phospholipid (PL) labels between lighter
      and heavier fractions of HDL and emulsion particles. The transfers of CO and PL
      labels between both light and heavy fractions of HDL and the emulsion particles
      were increased with increasing amounts of emulsion added to the incubations.
      Incubation with the d greater than 1.21 g/ml fraction from rat plasma resulted in
      only a small exchange of CO whereas PL exchange was similar to rabbit and human
      plasma. Retinyl palmitate label was not transferred from emulsion particles to
      the HDL fractions even in the presence of lipid transfer activity from rabbit or
      human plasma. The present study shows that the transfer protein-mediated
      exchanges of surface and core lipids between HDL and the triacylglycerol-rich
      lipoproteins are affected by the quantity of triacylglycerol-rich particles in
      the system. This mechanism may contribute to the inverse relationships between
      plasma triacylglycerol concentrations and HDL concentrations in normal and
      hypertriglyceridemic individuals.

PMID- 1998752
TI  - Sanitarian becomes ecologist: the new environmental health.

PMID- 1998753
TI  - Psychotropic drugs for problem children.

PMID- 1998754
TI  - Stress: another chimera.

PMID- 1998755
TI  - Hepatic and portal vein-thrombosis.

PMID- 1998757
TI  - Doctors and HIV: an international perspective.

PMID- 1998756
TI  - Second malignant tumours in head and neck cancer.

PMID- 1998758
TI  - "Muzzling" scientists?

PMID- 1998759
TI  - Changing disease patterns in patients with AIDS in a referral centre in the
      United Kingdom: the changing face of AIDS.
AB  - OBJECTIVE: To study the changes in morbidity, mortality, and survival patterns in
      a population of patients with AIDS in the United Kingdom from 1982 to 1989.
      DESIGN: A retrospective analysis of inpatient and outpatient records of patients
      with AIDS. SUBJECTS: 347 Patients with AIDS, predominantly homosexual or bisexual
      men. SETTING: Departments of immunology and genitourinary medicine, St Mary's
      Hospital, London. MAIN OUTCOME MEASURES: Presenting diagnosis of AIDS, occurrence
      of other opportunist diseases, cause of death, and survival since AIDS was
      diagnosed, in particular for those patients with Pneumocystis carinii pneumonia
      or Kaposi's sarcoma. RESULTS: The overall proportion of patients who developed P
      carinii pneumonia dropped from 56% (20/36) in 1984 to 24% (46/194) in 1989,
      although it has remained the index diagnosis in about half of new patients.
      Kaposi's sarcoma has decreased as index diagnosis from 30% (20/67) to 20% (15/74)
      over the same period, though the prevalence has remained constant at around 35%.
      P carinii pneumonia accounted for 46% (16/35) of known causes of death in 1986
      but only 3% (1/31) in 1989. Conversely, deaths due to Kaposi's sarcoma rose from
      14% (1/7) to 32% (10/31) between 1984 and 1989. Lymphoma accounted for an
      increased proportion of deaths among these patients with 16% (5/31) of deaths in
      1989. Their median survival increased from 10 months in 1984-6 to 20 months in
      1987. CONCLUSIONS: The changing patterns of disease in patients with AIDS have
      important implications both for health care provision and future medical
      research. Medical and nursing provision must be made for the increased morbidity
      of these diseases and the increased survival of these patients. Research should
      now be directed towards developing effective treatments for the opportunist
      infections which are currently more difficult to treat, the secondary
      malignancies of AIDS, as well as more effective immunorestorative treatments.
      Future changes in disease patterns must be recognised at an early stage so that
      resources can be adequately planned and allocated.

PMID- 1998760
TI  - Use of non-orthodox and conventional health care in Great Britain.
AB  - OBJECTIVE: To describe the characteristics of patients using non-orthodox health
      care and their pattern of use of conventional health care with respect to a
      particular problem. DESIGN: Postal survey of all 2152 practitioners of
      acupuncture, chiropractic, homeopathy, naturopathy, and osteopathy identified
      from 11 national professional association registers. Patients attending a
      representative sample of 101 responding practitioners completed questionnaires
      covering demographic characteristics, presenting problems, and use of the health
      service. SETTING: Practices of practitioners of non-orthodox health care in
      England, Scotland, and Wales. SUBJECTS: Qualified, non-medical practitioners of
      non-orthodox health care working in Great Britain and 2473 patients who had
      attended one of the sampled practitioners in an allocated time period between
      August 1987 and July 1988. RESULTS: An estimated 1909 practitioners were actively
      practising one of the study treatments in Great Britain in 1987. Of the estimated
      70,600 patients seen by this group of practitioners in an average week, most
      (78%) were attending with a musculoskeletal problem. Two thirds of the patients
      were women. Only 2% were aged under 16, but 15% were aged 65 or over. One in
      three patients had not received previous conventional care for their main
      problem; 18% were receiving concurrent non-orthodox and conventional care. Twenty
      two per cent of the patients reported having seen their general practitioner for
      any reason in the two weeks before the surveyed consultation. CONCLUSIONS:
      Patients of non-orthodox health care, as provided by this group of practitioners,
      had not turned their backs on conventional health care. Non-orthodox treatment
      was sought for a limited range of problems and used most frequently as a
      supplement to orthodox medicine.

PMID- 1998761
TI  - Comparison between perindopril and nifedipine in hypertensive and normotensive
      diabetic patients with microalbuminuria. Melbourne Diabetic Nephropathy Study
      Group.
AB  - OBJECTIVE: To compare the efficacy of angiotensin converting enzyme inhibition
      with calcium antagonism in diabetic patients with microalbuminuria. DESIGN:
      Randomised study of diabetic patients with microalbuminuria treated with
      perindopril or nifedipine for 12 months and monitored for one or three months
      after stopping treatment depending on whether they were hypertensive or
      normotensive. Patients were randomised separately according to whether they were
      hypertensive or normotensive. SETTING: Diabetic clinics in three university
      teaching hospitals. PATIENTS: 50 diabetic patients with persistent
      microalbuminuria. In all, 43 completed the study: 30 were normotensive and 13
      hypertensive; 19 had type I diabetes and 24 had type II diabetes. INTERVENTIONS:
      For 12 months 20 patients were given perindopril 2-8 mg daily and 23 were given
      nifedipine 20-80 mg daily. MAIN OUTCOME MEASURES: Albumin excretion rate, blood
      pressure, and glomerular filtration rate. RESULTS: Both perindopril and
      nifedipine significantly reduced mean blood pressure. During treatment there was
      no significant difference between those treated with perindopril and those
      treated with nifedipine with respect to albuminuria or mean blood pressure.
      Stopping treatment with both drugs was associated with a sustained increase in
      albuminuria and mean blood pressure. There was a significant correlation between
      mean blood pressure and albuminuria and also between the reduction in mean blood
      pressure and the decrease in albuminuria during treatment with both drugs. In
      hypertensive patients both drugs caused significant decreases in mean blood
      pressure and albuminuria. In normotensive patients there was no significant
      reduction in albuminuria with either regimen. CONCLUSIONS: In diabetic patients
      with microalbuminuria blood pressure seems to be an important determinant of
      urinary albumin excretion. Perindopril and nifedipine have similar effects on
      urinary albumin excretion, both preventing increases in albuminuria in
      normotensive patients and decreasing albuminuria in hypertensive patients.

PMID- 1998762
TI  - Oxygen desaturation in apparent and relative polycythaemia.

PMID- 1998763
TI  - Prescribing of psychotropic drugs to children and adolescents.

PMID- 1998764
TI  - C4 and plasma protein in hypertension during pregnancy with and without
      proteinuria.

PMID- 1998765
TI  - Detecting hypertension: screening versus case finding in Norway.
AB  - OBJECTIVE: Evaluation of detection of hypertension in adults in the county of
      Nord-Trondelag, Norway. DESIGN: Cross sectional survey with clinical follow up
      examinations. SETTING: Health survey by screening teams from the national health
      screening service, and examinations by all 106 general practitioners in the
      county. SUBJECTS: During 1984-6, 74,977 persons (88.1% of those aged 20 years and
      over) participated in the health survey. MAIN OUTCOME MEASURES: Hypertension
      (when assessed by standardised recording and by questionnaires on drug treatment
      for hypertension) according to the blood pressure thresholds used in the
      Norwegian treatment programme. Subjects positive on screening were grouped after
      clinical examination into treatment groups. RESULTS: In all, 2399 subjects were
      positive for hypertension. Before screening 6210 (8.3%) patients reported taking
      antihypertensive drugs and another 3849 (5.1%) had their blood pressure monitored
      regularly. All who screened positive were referred to their general practitioner
      and evaluated according to a standard programme. As a result, drug treatment was
      started in 406 (0.5%) participants screened and blood pressure monitoring in
      another 1007 (1.3%). Of all patients taking antihypertensive drugs after the
      screening, 6399 (94.0%) had been diagnosed before screening, and of those whose
      blood pressure was monitored after the screening, 79.3% had been diagnosed before
      screening. CONCLUSIONS: At the blood pressure screening thresholds used, and when
      hypertension is defined by an overall clinical diagnosis, the results indicate
      that general practitioners can find and diagnose hypertensive patients with the
      case finding strategy.

PMID- 1998767
TI  - Junior doctors' years: training, not education.

PMID- 1998766
TI  - Study of United Kingdom product licence applications containing new active
      substances, 1987-9.
AB  - OBJECTIVES: To investigate the fate of product licence applications containing
      new active substances in relation to their degree of innovation and therapeutic
      category. To assess the numbers of volunteers and patients exposed to a new
      active substance when marketing autorisation is first sought. DESIGN AND SETTING:
      Observational study of records for each licence application submitted to the
      United Kingdom licensing authority for marketing authorisation from 1987 to 1989.
      SUBJECTS: 118 product licence applications containing one or more new active
      substances. MAIN OUTCOME MEASURES: Success of application for product licence as
      assessed by the decision of the Committee on Safety of Medicines to advise the
      granting of a licence (with or without conditions) or provisionally advise its
      refusal on the grounds of quality, safety, or efficacy. Assessment of numbers of
      volunteers and patients exposed to each substance during premarketing studies and
      clinical trials, and the numbers of treated patients available for an assessment
      of safety. RESULTS: 118 relevant product licence applications were submitted
      during the review. Although 60% (52/86) of semi-innovative products fell into one
      of three therapeutic categories (cardiovascular, central nervous system, or anti
      infective agents), only 41% (13/32) of fully innovative products fell into these
      categories. 47 applications were granted (conditionally or unconditionally) but
      the success rate for fully innovative products (56%, 18/32) was greater than that
      for semi-innovative products (34%, 29/86). The number of volunteers and patients
      exposed to a new product at submission varied widely and tended to be greater for
      successful applications. CONCLUSION: The results suggest a broadening of the
      pharmaceutical industry's research and development programmes and that a more
      liberal licensing policy exists for fully innovative products than for semi
      innovative products. The relatively limited exposure of patients to new active
      substances at licensing underlines the importance of rigorous postmarketing
      surveillance.

PMID- 1998768
TI  - Attendance allowance.

PMID- 1998769
TI  - Compensation for medical accidents.

PMID- 1998770
TI  - Effects of discrimination on careers of British medical graduates.

PMID- 1998771
TI  - Renal artery stenosis.

PMID- 1998772
TI  - Bleeding tonsils.

PMID- 1998773
TI  - Hospital admissions for accidents in preschool children.

PMID- 1998774
TI  - Causes of fatal childhood accidents.

PMID- 1998775
TI  - Flat feet in children.

PMID- 1998776
TI  - Aerosols causing ocular trauma.

PMID- 1998777
TI  - Diagnostic utility of flumazenil in coma with suspected poisoning.

PMID- 1998778
TI  - We cannot afford an AIDS epidemic.

PMID- 1998779
TI  - 50 years on: the crush syndrome.

PMID- 1998780
TI  - Injuries due to chemical weapons.

PMID- 1998781
TI  - Screening for people with mental handicap.

PMID- 1998783
TI  - Juniors' hours.

PMID- 1998782
TI  - Vitamin A and measles in Third World children.

PMID- 1998784
TI  - Colin's story.

PMID- 1998785
TI  - Multiple sclerosis: nature or nurture?

PMID- 1998786
TI  - Picking up the tab for erythropoietin.

PMID- 1998787
TI  - Prospective or retrospective: what's in a name?

PMID- 1998788
TI  - Revisiting the internal market.

PMID- 1998789
TI  - Hormone replacement therapy and survival after surgery for ovarian cancer.
AB  - OBJECTIVE: To evaluate whether hormone replacement therapy affects survival in
      women who have undergone bilateral salphingo-oophorectomy because of epithelial
      ovarian cancer. DESIGN: Retrospective analysis by review of patients' notes and
      questionnaires completed by general practitioners to compare the overall survival
      and disease free survival in patients with ovarian cancer who did or did not
      receive hormone replacement therapy after diagnosis. Data were analysed by Cox
      regression, with hormone replacement therapy as a time dependent covariate
      because patients who received hormone replacement did so at different times after
      diagnosis. SETTING: Gynaecological oncology unit of Royal Marsden Hospital.
      PATIENTS: 373 patients aged 50 years or younger who attended the hospital from
      1972 to 1988. All of the women had undergone bilateral salpingoophorectomy for
      epithelial ovarian cancer. In all, 78 had received hormone replacement therapy,
      starting at a median of four months after diagnosis. INTERVENTION: A
      questionnaire was sent to the general practitioners of all patients who were not
      recorded as having received hormone replacement therapy. MAIN OUTCOME MEASURES:
      Overall survival and disease free survival. RESULTS: There was no significant
      difference in survival between women receiving hormone replacement therapy and
      those not receiving it after accounting for the effects of other known prognostic
      factors (stage of cancer, differentiation of tumour, histological results, and
      time to relapse). The relative risk of dying in those who received hormone
      replacement therapy was 0.73 (95% confidence interval 0.44 to 1.20). In addition,
      there was no significant difference in disease free survival (relative risk in
      those receiving hormone replacement therapy was 0.90; 95% confidence interval
      0.52 to 1.54). CONCLUSIONS: This study shows that hormone replacement therapy is
      unlikely to have a detrimental effect on the prognosis of patients with ovarian
      cancer, but this would be shown conclusively only by a randomised controlled
      trial.

PMID- 1998790
TI  - Spontaneous pneumothorax: marker gas technique for predicting outcome of manual
      aspiration.
AB  - OBJECTIVE: To determine whether in a patient with spontaneous pneumothorax the
      presence or absence of a pleural leak can be shown at the time of manual
      aspiration by use of a marker gas. Also, to find out if the technique can predict
      whether manual aspiration will be successful, hence avoiding the need for
      intercostal tube drainage. DESIGN: Prospective study of 25 episodes of
      pneumothorax during which patients breathed air from a Douglas bag that contained
      chlorofluorocarbon gases from a metered dose inhaler while the pneumothorax was
      aspirated. SETTING: Medical unit of a district general hospital. PATIENTS: 22
      patients who presented over nine months with acute pneumothorax. MAIN OUTCOME
      MEASURES: Presence or absence of chlorofluorocarbon marker gases in the aspirate.
      Presence or absence of sustained re-expansion of the affected lung in the chest
      radiograph. RESULTS: Marker gas was detected in the aspirate from 16 out of 25
      pneumothoraces. Of these, 13 required intercostal tube drainage because of
      failure of the lung to re-expand. Marker gas was not detected in nine cases, and
      in all of these cases manual aspiration resulted in sustained re-expansion of the
      lung. CONCLUSIONS: The presence or absence of a pleural leak during manual
      aspiration of spontaneous pneumothorax can be shown by using this technique. The
      absence of marker gas in the aspirate implies that manual aspiration will be
      successful, whereas its presence predicts, in most cases, either failure of
      manual aspiration to expand the lung or early re-collapse of the lung.

PMID- 1998791
TI  - Usefulness of immunotherapy in patients with severe summer hay fever uncontrolled
      by antiallergic drugs.
AB  - OBJECTIVE: To evaluate the efficacy and safety of immunotherapy
      (hyposensitisation) in patients with severe summer hay fever. DESIGN: A
      randomised, double blind, placebo controlled study of a biologically standardised
      depot grass pollen extract. SETTING: Allergy clinic, Royal Brompton and National
      Heart Hospital, London. PATIENTS: 40 adults (mean age 35 years) with a history of
      severe grass pollen allergy uncontrolled by standard antiallergic drugs. Patients
      with perennial asthma were specifically excluded. INTERVENTION: Patients were
      randomised to receive either an active preparation (Alutard SQ, a grass pollen
      (Phleum pratense) extract) or placebo at a rate of two subcutaneous injections a
      week in increasing doses until a maintenance dose was reached. This maintenance
      dose was given once a month. MAIN OUTCOME MEASURES: Clinical efficacy was
      evaluated by symptom and drug diary cards, visual analogue scores during the
      grass pollen season, and a postseasonal assessment by the patients and a doctor.
      Conjunctival and skin sensitivity to local allergen provocation was measured
      before and after eight months of treatment. RESULTS: There was a highly
      significant decrease (median Alutard SQ v median placebo (95% confidence interval
      for difference between medians] in total symptom scores (p=0.001) in the Alutard
      SQ treated group (360 v 928 (238 to 825]. Significant differences were also found
      in total drug use (p=0.002, 129 v 627 (178 to 574]. Visual analogue symptom
      scores were also reduced in the active group (p=0.02, 2.2 v 5.5 (-4.8 to -0.5].
      The postseasonal assessment, by either the doctor or the patients, showed a large
      improvement (p less than 0.001) in favour of Alutard SQ. Provocation tests showed
      a greater than 10-fold reduction for the active group in immediate conjunctival
      allergen sensitivity (p=0.001), a 40% decrease in early phase response (p=0.02),
      and a 57% decrease in the late phase (p=0.001) cutaneous response after
      intradermal allergen. A total of 523 active injections were given. There was one
      systemic reaction at 10 minutes after injection, which was rapidly reversed with
      intramuscular adrenaline. There was one mild delayed urticarial reaction at 2 1/2
      hours. CONCLUSION: Immunotherapy is effective in patients with severe summer hay
      fever, but immediate anaphylactic reactions limit its use to specialised centres.
      Patient selection is extremely important, and chronic perennial asthma should be
      specifically excluded. As serious reactions occur within minutes a two hour wait
      for all patients after each injection seems unnecessary.

PMID- 1998793
TI  - Side effects expected and experienced by women receiving chemotherapy for breast
      cancer.

PMID- 1998792
TI  - Changes in haemostasis after stopping the combined contraceptive pill:
      implications for major surgery.
AB  - OBJECTIVE: To investigate the changes in haemostasis in the three months
      immediately after stopping the combined contraceptive pill. DESIGN: Prospective
      randomised study. SETTING: Family planning centre in London. SUBJECTS: 24 women
      aged 35-45 investigated before, during, and after six months' use of combined
      oral contraceptives containing 30 micrograms ethinyl oestradiol together with the
      progestogens desogestrel or gestodene. MAIN OUTCOME MEASURES AND RESULTS: Blood
      samples were taken immediately before and after six months of oral contraceptive
      use and one, two, four, six, eight, and 12 weeks after the pill had been stopped.
      During the six months of oral contraceptive use the plasma concentration of
      factor X and fibrinogen increased and that of antithrombin III decreased. Between
      two and six weeks after stopping the pill a rebound phenomenon occurred with
      plasma concentrations of antithrombin III increasing (mean change from baseline
      at two weeks 0.06 IU/l and at six weeks 0.10 IU/l) and fibrinogen decreasing
      (0.26 g/l change at two weeks and 0.40 g/l at six weeks). Factor X concentrations
      fell gradually and the values at eight weeks were not significantly different
      from those found before the combined pill was started. CONCLUSION: The combined
      pill should be stopped at least four weeks before major surgery, which carries
      the risk of postoperative thrombosis, to allow the potentially prothrombotic
      haemostatic changes that occur during its use to be corrected.

PMID- 1998794
TI  - Effects of withdrawing erythropoietin.

PMID- 1998795
TI  - Study of general practice consultations and menopausal problems. Oxford General
      Practitioners Menopause Study Group.
AB  - OBJECTIVE: To investigate the nature of work related to the menopause in general
      practice. DESIGN: Questionnaire study over six months among general practitioners
      after each consultation with a woman aged 40-69 at which issues related to the
      climacteric had been discussed. SETTING: 9 General practices in the Oxford area.
      SUBJECTS: 416 Women who had 572 consultations. MAIN OUTCOME MEASURES: Age,
      menopausal state, and first or subsequent consultation. Symptoms were classified
      together with the treatment and the outcome of the consultation. RESULTS: The
      consultation rate varied greatly between practices, the overall rate being 4.4%.
      There were many premenopausal women and women in their 60s presenting; women with
      hysterectomies presented more often--36% (37/103) of women with hysterectomies
      had more than one consultation compared with 26% (38/144) for premenopausal women
      and 24% (38/155) for postmenopausal women. 409 women had symptoms and 218 were
      prescribed oestrogen treatment. 156 of the consultations involved discussion and
      advice only. Only four women were referred to a local specialist clinic.
      CONCLUSION: There is a low overall use of hormone replacement therapy in the
      general postmenopausal population despite the recent media coverage of its
      benefits in the prevention of osteoporosis and subsequent fractures.

PMID- 1998797
TI  - What will the medical director do?

PMID- 1998796
TI  - Nosocomial outbreak of cryptosporidiosis in AIDS patients.
AB  - OBJECTIVE: To describe a nosocomial outbreak of cryptosporidiosis during four
      months after June 1989. SETTING: A department of infectious diseases in
      Copenhagen, seeing about half the patients with AIDS in Denmark. SUBJECTS: 73 HIV
      antibody negative subjects and 60 antibody positive subjects admitted as
      inpatients during the transmission period of the outbreak (20 June-14 August), of
      whom 18 (17 with AIDS, one with AIDS related complex), developed
      cryptosporidiosis. Two further HIV negative subjects (one departmental secretary,
      one visiting relative) developed cryptosporidiosis. MAIN OUTCOME MEASURES:
      Cryptosporidia in stool samples, clinical symptoms, CD4 cell count, HIV antigen
      concentration, chemotherapeutic treatment. RESULTS: The source of the outbreak
      was identified as ice from an ice machine in the ward, contaminated by an
      incontinent, psychotic patient with cryptosporidiosis picking out ice for cold
      drinks. The mean incubation time was at least 13 days-that is, twice that in HIV
      negative patients. Of the 18 patients with AIDS who developed cryptosporidiosis,
      five recovered, two were symptomless carriers, three died of unrelated causes,
      and eight died after prolonged diarrhoea. Among the 57 exposed HIV antibody
      positive inpatients (excluding two patients and the index case with
      cryptosporidiosis diagnosed elsewhere), significantly more of those who developed
      symptomatic cryptosporidiosis received oral sulphonamides than those who did not
      (91%, 10/11 v 48%, 21/44, p less than 0.05). CONCLUSIONS: The clinical and
      epidemiological findings indicate that infection was the consequence of very
      small inocula. Increased sensitivity to cryptosporidiosis may be an unrecognised
      side effect of oral sulphonamide treatment in patients with AIDS.

PMID- 1998798
TI  - How to do it: organize a reunion of your undergraduate classmates.

PMID- 1998799
TI  - Rationing health care.

PMID- 1998800
TI  - Trial by anecdote.

PMID- 1998801
TI  - Homoeopathy: medicine or magic?

PMID- 1998802
TI  - Congenital rubella in the Asian community.

PMID- 1998803
TI  - Flouting the guidelines.

PMID- 1998804
TI  - Bell ringer's bruises and broken bones.

PMID- 1998805
TI  - Diagnosis of Alzheimer's disease.

PMID- 1998806
TI  - Diagnostic utility of flumazenil in coma with suspected poisoning.

PMID- 1998807
TI  - Should religious circumcisions be performed on the NHS?

PMID- 1998808
TI  - Archives of contemporary medicine and science.

PMID- 1998809
TI  - Gulf war casualties.

PMID- 1998810
TI  - Immediate hypersensitivity to aztreonam and imipenem.

PMID- 1998811
TI  - Another quirk of quinine.

PMID- 1998812
TI  - Hospital libraries in perspective.
AB  - The proliferation of hospital libraries since World War II has created a
      generation of librarians who take for granted the existence of libraries in
      hospitals. A literature review for the first half of the twentieth century
      presents a picture of uncertainty and struggle for identity for the hospital
      library. Then as now, hospital libraries reflect the institutions within which
      they operate. A brief history of the development of the American hospital
      provides a context for describing the various roles that the hospital library has
      played within its parent institution during the twentieth century. Some personal
      reflections on working in a hospital library are also presented.

PMID- 1998813
TI  - Use of information resources by veterinary practitioners.
AB  - Veterinary practitioners are often isolated from easy access to information in
      medical or hospital libraries, making necessary the use of a variety of
      information resources. A survey was conducted to assess the extent to which
      various information resources were used within the veterinary profession. Most
      responding veterinarians were small-animal practitioners who used the veterinary
      literature, colleagues, diagnostic laboratories, continuing education courses,
      association meetings, and pharmaceutical representatives as sources of
      information. Books and other practitioners were the preferred information source
      in critical-care situations, followed closely by diagnostic laboratories and
      journals. For keeping up-to-date with current advances in veterinary medicine,
      journals, books, other practitioners, and continuing education were used.
      University extension services, veterinary medical libraries, and computer
      applications to information use were not important resources ot most of the
      respondents. Many veterinarians indicated that they would use library services if
      they knew more about them. With the trend toward computerization in veterinary
      practice, it is possible for libraries to help reduce the information isolation
      of many veterinary practices.

PMID- 1998814
TI  - Two opinions.

PMID- 1998815
TI  - "The pleasures of the presidency: some personal reflections on serving as
      president".

PMID- 1998816
TI  - Clinical medical librarian: the last unicorn?
AB  - In the information age of the 1990s, the clinical medical librarian (CML)
      concept, like many other personalized library services, is often criticized as
      being too labor-intensive and expensive; others praise its advantages. To
      determine the attitudes of medical school library directors and clinical
      department heads toward implementation and feasibility of a CML program, forty
      randomly selected medical schools were surveyed. A double-blind procedure was
      used to sample department heads in internal medicine, pediatrics, and surgery, as
      well as health sciences library directors identified by the Association of
      Academic Health Sciences Library Directors (AAHSLD) annual statistics. The survey
      instrument was designed to measure responses to the following attitudinal
      variables: acceptance and nonacceptance of a CML program; importance to patient
      care, education, and research; influence on information-seeking patterns of
      health care professionals; ethical issues; CML extension services; and costs.
      Seventy-nine usable questionnaires out of a total of 120 (66%) were obtained from
      clinical medical personnel, and 30 usable questionnaires out of a total of 40
      (75%) were obtained from medical school library directors. Survey results
      indicated significant differences between clinical medical personnel and library
      personnel regarding attitudes toward CML influence on information-seeking
      patterns, ethics, alternative CML services, and costs. Survey results also
      indicated a continuing strong support for CML programs in the medical school
      setting; however, differences of opinion existed toward defining the role of the
      CML and determining responsibility for funding.

PMID- 1998817
TI  - Health professionals' use of documents obtained through the Regional Medical
      Library Network.
AB  - The Pacific Southwest Regional Medical Library Service (PSRMLS) studied how
      health professionals use documents obtained through the regional medical library
      (RML) network and how various factors, such as delivery time, affected that use.
      A random sample of libraries in Region 7 of the RML network was selected to
      survey health professionals who had received documents through the interlibrary
      loan (ILL) network. The survey provided data about the purposes for which health
      professionals requested documents, how the immediacy of need for the items
      affected their usefulness, what effect the obtained information had on the health
      professionals' work, and whether the illustrations represented an important part
      of the information content of the items. Survey results provided a positive
      assessment of the ILL network. Results also verified the basic value of the
      materials provided to health professionals through ILL and identified some areas
      for consideration in future network development. Users of the documents indicated
      that the network works efficiently and effectively to provide timely and useful
      information needed by health professionals. Technological developments in
      electronic information transmission and imaging will further enhance network
      operation in the future.

PMID- 1998818
TI  - Biotechnology awareness study, Part 1: Where scientists get their information.
AB  - A model study, funded by the National Library of Medicine (NLM) and conducted by
      the Southeastern/Atlantic Regional Medical Library (RML) and the University of
      Maryland Health Sciences Library, attempted to assess the information needs of
      researchers in the developing field of biotechnology and to determine the
      resources available to meet those needs in major academic health sciences
      centers. Nine medical schools in RML Region 2 were selected to participate in a
      biotechnology awareness study. A survey was conducted of the nine medical school
      libraries to assess their support of biotechnology research. To identify the
      information needs of scientists engaged in biotechnology-related research at the
      schools, a written survey was sent to the deans of the nine institutions and
      selected scientists they had identified. This was followed by individual, in
      depth interviews with both the deans and scientists surveyed. In general,
      scientists obtained information from three major sources: their own experiments,
      personal communication with other scientists, and textual material (print or
      electronic). For textual information, most study participants relied on personal
      journal subscriptions. Tangential journals were scanned in the department's
      library. Only a few of these scientists came to the health sciences library on a
      regular basis. Further, the study found that personal computers have had a major
      impact on how biotechnologists get and use information. Implications of these
      findings for libraries and librarians are discussed.

PMID- 1998819
TI  - Biotechnology awareness study, Part 2: Meeting the information needs of
      biotechnologists.
AB  - The second part of the biotechnology awareness study focused on health sciences
      libraries and how well they are meeting the needs of biotechnologists working in
      the study's nine medical centers. A survey was conducted over a three-month
      period to assess the demand for biotechnology-related reference services at nine
      libraries and the sources the librarians used to answer the questions. Data on
      monographic and current serial holdings were also collected. At the end of the
      survey period, librarians were asked for their perceptions about biotechnology
      research at their institutions and in their geographic areas. Their responses
      were compared to the responses the scientists at the nine schools gave to the
      same or similar questions. Results showed few biotechnology-related reference
      questions were asked of the librarians. The recorded questions dealt with a range
      of biotechnology subjects. MEDLINE was used to answer 77% of the questions
      received during the survey period. More detailed notes in MeSH and a guide to
      online searching for biotechnology topics were suggested by the librarians as
      ways to improve reference service to this group of researchers. Journal
      collections were generally strong, with libraries owning from 50% to 87% of the
      titles on a core list of biotechnology journals compiled for this study. All
      libraries subscribed to the five titles most often cited by the scientists
      surveyed. Generally, librarians were unaware of the biotechnology-related
      research being done on their campuses or in their geographic areas.

PMID- 1998820
TI  - Remote access to electronic library services through a campus network.
AB  - The Health Science Library at University of Tennessee (UT), Memphis has taken
      advantage of a campuswide network for the purpose of providing enhanced access to
      library services. With a terminal or microcomputer, members of the UT Memphis
      community can use an electronic menu system to complete photocopy, interlibrary
      loan, and computer literature search request forms; leave messages or sign up for
      library workshops; use electronic mail to receive citations and abstracts from
      computer literature searches; use an electronic bulletin board to scan the
      library's new acquisitions lists, library hours, services, and policies; and use
      bibliographic retrieval software to search the library's locally mounted
      databases. Remote access to library services and electronic resources, which is
      available twenty-four hours a day, could potentially save users time and the
      institution money. Remote access, however, is intended to supplement, not to
      supplant or discourage, in-house library use.

PMID- 1998821
TI  - The evolution and installation of an in-house CD-ROM LAN.

PMID- 1998822
TI  - Medical students as CD-ROM end-user trainers.

PMID- 1998824
TI  - Recent health sciences library building projects.
AB  - Librarians were asked to submit information for an annual architectural feature
      on projected, partially funded, architect selected, nearly designed, bid
      completed, under construction, almost finished, or recently completed library
      construction. Thirty-two health sciences libraries reported expansion,
      construction of new facilities, or construction planning. Seven building programs
      were identified as projected, or in predesign or design stages. Five projects
      were new, stand-alone structures in which the library occupies all or a major
      portion of the space. Nine projects were part of new construction for several
      separately administered units in which the library is a major tenant. Eleven
      projects involved additions to or renovations of existing space. Seven projects
      are presented as illustrative of current library construction.

PMID- 1998823
TI  - Problems encountered by clinical end users of MEDLINE and GRATEFUL MED.

PMID- 1998825
TI  - Marketing the hospital library to physicians: one approach.

PMID- 1998826
TI  - The scholarly publishing imbroglio: a personal view.

PMID- 1998827
TI  - Thoughts about librarians as defined by Mark Plaiss.

PMID- 1998828
TI  - Sic transit gloria bibliothecarii.

PMID- 1998829
TI  - Paraprofessionals and reference.

PMID- 1998830
TI  - Library statistics.

PMID- 1998831
TI  - MEDLINE and BIOSIS.

PMID- 1998832
TI  - Magnetic resonance angiography of abdominal vessels: early experience using the
      three-dimensional phase-contrast technique.
AB  - Based on three-dimensional acquisition of three sequences sensitive to one flow
      direction, abdominal magnetic resonance phase-contrast angiography (MRA) was
      performed in 13 volunteers and 20 patients. The subjects received no
      antiperistaltic medication and were allowed to breath normally during the three
      acquisition periods of 11 minutes. The frequency of demonstration of the normal
      aorta, superior mesenteric and right and left renal arteries was
      100%/100%/91%/100%, and of the inferior vena cava, splenic, superior mesenteric
      and portal veins was 92%/67%/92%/100%, respectively, whereas other abdominal
      vessels were seen less constantly. In renal artery stenosis or occlusion, MRA
      detected eight out of nine pathological arteries, missed only a minimal stenosis
      and was never false positive. In all 10 cases of portal hypertension, MRA
      demonstrated the venous collaterals detected by conventional angiography and in
      six cases showed more collaterals, particularly paravertebral vessels. A Budd
      Chiari syndrome was investigated as well. If the accuracy of MRA can be proved in
      larger studies, it may become an important diagnostic tool in evaluating
      abdominal vascular pathology, such as renal artery stenosis or portal
      hypertension.

PMID- 1998833
TI  - Ultrasound in the investigation of the right iliac fossa mass.
AB  - Patients presenting with a right iliac fossa (RIF) mass are a diagnostic problem.
      The objective of this study was to assess the role of ultrasound (US) in their
      investigation. A prospective series of 50 patients presenting with a clinically
      suspected RIF mass was examined by US and the finding correlated with the final
      diagnosis. There was a positive finding in 34 patients (68%). Ultrasound
      correctly identified the organ of origin in 33 (97%) and was able to guide the
      patients' further management. In 12 cases no abnormality was found in the RIF, of
      which 11 had no positive findings at follow-up and one was shown to have an
      unrelated abnormality at laparotomy. In four cases the findings were due to
      normal variants. Ultrasound is the imaging modality of first choice in patients
      presenting with a RIF mass.

PMID- 1998834
TI  - Determinations of organ doses and effective dose equivalents from computed
      tomographic examination.
AB  - The organ or tissue doses were determined with a phantom measurement for 12 types
      of CT scanners widely used in Japan. Two types of thermoluminescent dosimeters
      were used for the dose determinations in a Rando woman phantom. The effective
      dose equivalents recommended by the International Commission on Radiological
      Protection were calculated using the measured organ or tissue doses. It was found
      that the CT scanners currently available give quite different organ or tissue
      doses. When selecting the optimum technical factors for scanning, therefore, it
      is important to take into consideration the balance of the image quality and the
      radiation exposure to patients.

PMID- 1998835
TI  - Carcinoma of the breast: measurement and the management of treatment. I. The
      value of the data.
AB  - This is the first of a series of papers in which we shall explore some insights
      into the biological changes which accompany the treatment of human tumours which
      may be obtained through estimation of volume changes in relation to treatment. We
      have adopted a working hypothesis that regression slopes reflect the composition
      of individual tumours and, indirectly, their intrinsic growth rate rather than
      the effectiveness of treatment. The breast has proved to be a suitable site for
      measurement and our interpretation of the results has led to the development of a
      new style of management for carcinoma of the breast: measurement based sequential
      therapy (MBST). In this paper the method of measurement and detailed statistical
      evaluation of the quality of the data from 262 patients (263 tumours) is
      presented. Exponential regression lines have been fitted to describe volume
      changes in relation to treatment by radiation, chemotherapy and hormones. A
      simple classification of steepness of slopes is introduced.

PMID- 1998836
TI  - Selective uptake of toxic nucleoside (125IUdR) by resistant cancer.
AB  - We report uptake of a thymidine analogue 125-Iodine-5-iodo-2'-deoxyuridine
      (125IUdR) by nude mice bearing human xenografts of choriocarcinoma or colonic
      cancer. When 125IUdR was given alone, uptake by intestinal tissues was 5-10 times
      greater than by the tumours as measured by tissue gamma counting. This ratio was
      reversed when hydroxyurea or cytosine arabinoside were used as inhibitors of
      ribonucleotide reductase and were given in combination with 5-fluorouracil or
      methotrexate to inhibit thymidine synthesis shortly before injecting 125IUdR.
      Counting the radioactivity in tissues removed 24 hours after 125IUdR gave tumour
      to highest normal tissue ratios of up to 15:1, but the corresponding nuclear
      grain counts, which is probably a more reliable indicator of selective uptake
      into DNA, were in excess of 100:1. The addition of unlabelled IUdR to the regimen
      only reduced the uptake of 125IUdR when given in relatively large amounts. For
      this approach to be exploited it is concluded that the tumour must be resistant
      at the cell level to the inhibitor of DNA synthesis either de novo or as a result
      of prior exposure to it. This inhibitor can then be used to block uptake of the
      potentially toxic nucleoside analogue by normal renewal tissues while it is taken
      up by the resistant cancer cells. By inhibiting synthesis of the corresponding
      normal nucleosides with inhibitors to which the cancer cells are not resistant,
      incorporation of the toxic analogues into tumour DNA was enhanced. Although
      125IUdR is a convenient agent for exploring this approach and is highly cytotoxic
      when incorporated in DNA, the clinical potential of reverse role chemotherapy
      probably lies with the development of toxic non-radioactive nucleoside analogues.

PMID- 1998838
TI  - The effect of sodium iothalamate on the vascular resistance of the isolated
      perfused rat kidney.
AB  - The direct effects of sodium iothalamate on renal vascular resistance (RVR) were
      examined using the isolated perfused rat kidney experimental model. A
      concentration-dependent biphasic change in RVR was produced with the hyperosmolar
      solution of sodium iothalamate [(Conray 420), 420 mgI/ml, 2500 mOsmol/kg/H2O].
      The response characterized by an initial fall followed by a prolonged increase in
      RVR on discontinuation of the iothalamate infusion. No significant change in RVR
      was observed when iothalamate was infused as an iso-osmotic solution (60 mgI/ml,
      280 mOsmol/kg/H2O) at a rate of 0.525 ml/min. to produce a concentration of 4.2
      mgI/ml in the renal perfusate. We conclude that sodium iothalamate can exert
      direct biphasic effects on RVR which are mediated by its hyperosmolality rather
      than its chemical content.

PMID- 1998837
TI  - Tissue dose estimates following the selective uptake of 125IUdR and other
      radiolabelled thymidine precursors in resistant tumours.
AB  - For the purposes of evaluation of the therapeutic potential of the
      radiohalogenated thymidine analogue 125IUdR, estimation of the radiation dose to
      the tumour cells and normal tissues is important. To determine the dose to any
      tissue from the radionuclide 125I is not simple, since the major emissions are
      very short-range Auger electrons. The cytotoxicity of 125I is strongly dependent
      on the position of the decay relative to the DNA, the principal target for cell
      sterilization. Estimates of the cytotoxicity of 125I based on the traditional
      MIRD recommended formulation (ICRU Report 32, 1979) may produce gross
      underestimates if it is incorporated into the DNA via the thymidine precursor
      125IUdR. In this work, tissue count and autoradiography (ARG) data from studies
      by Bagshawe et al were used to estimate tissue doses following the administration
      of 125IUdR to LS174/T (a colorectal carcinoma) and CC3 (a choriocarcinoma) tumour
      bearing animals, after a hydroxyurea block of the normal tissue turnover. The
      tumour cell toxicity is estimated from ARG data on the degree of 125I
      incorporation into the cell nucleus. Major drawbacks with 125I for this type of
      therapy are the long 60-day half-life, leading to radiological and waste disposal
      problems and the extreme short range of the radiotoxic effects. Possible
      alternative radiohalogens, 13I, 77Br, 131I and 211At, are suggested in place of
      125I in the thymidine analog iododeoxyuridine. Dose calculations are performed
      and cytotoxicities estimated on the assumption that their biological retention
      characteristics are the same as for 125IUdR.

PMID- 1998839
TI  - Splenic calcification following treatment of Hodgkin's disease.

PMID- 1998840
TI  - Well ventilated bullae: a potential confusion on ventilation/perfusion scanning.

PMID- 1998841
TI  - Cranio-facial melorheostosis: case report and review of the literature.

PMID- 1998842
TI  - Lymphangiohaemangioma of the mediastinum.

PMID- 1998843
TI  - Detection of focal nodular hyperplasia with liver colloid single photon emission
      computed tomography: a case report and review of the literature.

PMID- 1998844
TI  - Broad-beam transmission data in lead for scattered radiation produced at
      diagnostic energies.

PMID- 1998846
TI  - The physical dimensions of the compressed breast.

PMID- 1998845
TI  - Retroperitoneal haematoma and pelvic haematoma following orchidectomy.

PMID- 1998848
TI  - Double-blind randomized trial of perioperative fibrinolytic enhancement for
      femoropopliteal bypass.
AB  - Patients with rest pain or acute peripheral arterial thrombosis are known to have
      impaired endogenous fibrinolysis, which is associated with an increased risk of
      early vascular graft thrombosis. This risk is exacerbated by the fibrinolytic
      shutdown which is known to occur after major surgery. Stanozolol, which has been
      demonstrated to enhance endogenous fibrinolysis, was therefore used in an attempt
      to prevent this perioperative fibrinolytic shutdown and so enhance graft patency.
      Twenty-seven patients were randomized to receive either 50 mg stanozolol or
      placebo intramuscularly 24 h before operation, followed by a 6 week course of
      either 5 mg stanozolol or placebo orally, twice daily. On the second day after
      operation, 10-11 MBq of autologous 111indium-labelled platelets were injected,
      with scanning over the graft on the 3 following days. Despite using a large depot
      of stanozolol, significant effects, such as raised plasminogen (P less than
      0.001), reduced fibrinogen (P less than 0.001) and reduced euglobulin lysis time
      (P less than 0.001), were not seen until the seventh day after operation, with
      maximum benefit at 6 weeks. This was reflected in the 111indium-labelled platelet
      deposition studies. The placebo group had a progressive increase in platelet
      deposition on all 3 days. In contrast, those receiving stanozolol showed a lower,
      static picture of deposition. However, these changes did not attain statistical
      significance. Three patients experienced early graft thrombosis, two in the
      placebo group and one in the stanozolol group. Only an incomplete inhibition of
      the perioperative fibrinolytic shutdown was achieved. Much longer preoperative
      courses are thus required to allow the maximum effect to be present at the most
      crucial time. At present, perioperative fibrinolytic enhancement does not appear
      to be a practical proposition, and we must await the development of new safer and
      more potent agents.

PMID- 1998847
TI  - Recurrence of Crohn's disease after resection.
AB  - Recurrent Crohn's disease develops in most patients after surgical resection if
      the patient is followed for sufficient time. This review examines various aspects
      of recurrent Crohn's disease. It is concluded that Crohn's disease is a diffuse
      condition of the gastrointestinal tract and that radical resection of Crohn's
      disease does not prevent recurrence. Assorted factors thought to be associated
      with recurrence are examined and the relevance of these factors to the surgeon
      treating Crohn's disease is discussed.

PMID- 1998849
TI  - Role of phenytoin in healing of large abscess cavities.
AB  - The promotion of healing of large abscess cavities attained with topical
      phenytoin was evaluated in controlled studies of clinical and experimental
      wounds. In the clinical abscess cavities, phenytoin application in 20 patients
      compared with conventional treatment in 20 patients resulted in earlier
      separation of slough, decrease in oedema, control of pain and overall enhanced
      healing. The mean(s.d.) rate of reduction of wound area was 2.02(0.48) cm2/day in
      the phenytoin group versus 1.58(0.51) cm2/day in controls (P less than 0.05) on
      day 10, and 1.8(0.32) cm2/day versus 1.19(0.21) cm2/day (P less than 0.01) on day
      20. The mean volume reduction rates at both the 10th and 20th day were 0.48(0.01)
      cm3/day for phenytoin versus 0.32(0.04) cm3/day for controls; (P less than
      0.005). By day 20, 17 of the patients treated with phenytoin were rated as having
      healed completely, compared with only one of the controls. In a standardized
      guinea-pig model of the clinical abscess cavity, which included inoculation of
      the wound with Bacillus proteus and Klebsiella pneumoniae, an enhanced healing
      rate was also observed (at 7 days 0.40(0.05) cm2/day with phenytoin versus
      0.21(0.08) cm2/day in controls; P less than 0.005). All eight of the animals
      treated with phenytoin healed by day 21, compared with one of the eight controls.
      Biopsies of wounds treated with phenytoin showed less inflammation, no necrosis,
      and enhanced neovascularization, collagen deposition and fibroblast proliferation
      compared to controls. Bacterial colonies also decreased more rapidly with the use
      of phenytoin.

PMID- 1998850
TI  - Postoperative hypophosphataemia and muscle function.
AB  - Muscle function tests of the triceps brachii muscle were performed before
      operation and on the third postoperative day in ten patients undergoing elective
      cholecystectomy. Electromyograms (EMGs) were recorded by surface electrodes
      during sustained isotonic and isometric muscle contraction with a constant force
      of 20 per cent of the preoperative maximal voluntary contraction. Root-mean
      square of the EMG was calculated together with the neuromuscular efficiency and
      measures of the fatiguability. These parameters were compared with changes in the
      simultaneously measured serum phosphate concentrations. Mean (s.e.m.)
      neuromuscular efficiency measured after 32-40 s of muscle contraction decreased
      14(5) per cent after operation (P less than 0.01), whereas the mean fatiguability
      of the muscle was unchanged. Mean serum phosphate concentration was 0.87(0.06)
      mmol/l before operation and 0.79(0.06) mmol/l 3 days after the operation (P
      greater than 0.05). Two patients developed severe postoperative hypophosphataemia
      (serum phosphate concentration less than 0.50 mmol/l). Postoperative muscle
      function deterioration was not associated with changes in the serum phosphate
      level (P greater than 0.10; r = 0.03). We conclude that patients undergoing
      cholecystectomy develop postoperative deterioration in skeletal muscle function,
      which is not associated with serum phosphate concentration.

PMID- 1998851
TI  - Importance of the omentum in the development of intra-abdominal metastases.
AB  - Areas of trauma are preferred sites for metastatic tumour growth. In extensive
      intra-abdominal tumour recurrence the omentum is invariably involved. The
      importance of the omentum in the development of tumours at sites of intra
      abdominal trauma has been investigated. Colonic anastomoses were performed in
      Hooded-Lister rats with and without omentectomy. Animals received intraluminal or
      intraperitoneal injections of a syngeneic tumour. With intraluminal injection,
      tumour occurred at the anastomosis and in the omentum in 38 and 43 per cent of
      animals respectively but following omentectomy the values were 14 and 9 per cent
      (omental remnant). With intraperitoneal administration tumour occurred in 53 per
      cent at the anastomosis and in 79 per cent in the omentum compared with 16 and 29
      per cent (in omental remnant) following omentectomy. In this model a reduced
      ability of an anastomosis to support 'seeded' tumour following removal of the
      omentum is demonstrated and the development of local recurrence from spilled
      tumour cells during operation may be enhanced by, or be dependent on, the
      proximity of the omentum.

PMID- 1998852
TI  - Aetiology of venous ulcers.

PMID- 1998853
TI  - Reducing renal ischaemia during transplantation.

PMID- 1998854
TI  - Colorectal liver metastases.

PMID- 1998855
TI  - Primary gastric carcinoids.

PMID- 1998856
TI  - Proximal gastric vagotomy: follow-up at 10-20 years.
AB  - From August 1969 to December 1989, 600 patients had elective proximal gastric
      vagotomy for duodenal ulceration with an operative mortality of 0.2 per cent. Of
      these, 372 patients had surgery over 10 years ago. Three hundred and forty-two
      patients survived for more than 10 years and, in a prospective study, 305 were
      reviewed, forming the basis of this 10-20-year follow-up report. Forty-six (15
      per cent) have had recurrent ulceration; 80 per cent of these developed symptoms
      within 5 years and no patient has had recurrence after 13 years. Although 29
      patients required reoperation for recurrent ulceration, the current patient
      satisfaction rate for Visick grades I and II is 92 per cent. Only two patients
      required reoperation because of gastric stasis. It is concluded that proximal
      gastric vagotomy is a safe and satisfactory first choice operation for duodenal
      ulceration.

PMID- 1998857
TI  - Formation of a loop stoma.

PMID- 1998859
TI  - The dog in the night time.

PMID- 1998858
TI  - Gastric adaptive relaxation and symptoms after vagotomy.
AB  - Gastric adaptive relaxation is reported to be impaired after vagotomy. This
      abnormality has been implicated in the pathogenesis of postvagotomy symptoms, but
      no association has previously been demonstrated between the two. Gastric adaptive
      relaxation was measured in 15 healthy volunteers and 33 patients more than 1 year
      after highly selective vagotomy or truncal vagotomy and drainage. Seventeen
      patients were asymptomatic. The remainder were symptomatic including seven
      patients with persistent diarrhoea. Fasted subjects were intubated with a Ryle's
      tube containing a pressure microtransducer within a flaccid (800 ml) plastic bag.
      Gastric corpus-fundus pressure was recorded during distension of the bag with air
      (15 ml/s) over 30 s. Pressure indices were derived from the areas under the
      pressure curves. Median (range) pressure indices were: healthy volunteers 12.7
      (7.5-17.1) cmH2O, highly selective vagotomy 14.0 (9.8-15.9) cmH2O (n.s.), truncal
      vagotomy and drainage 14.5 (8.6-26.8) cmH2O (P = 0.04). All patients with
      diarrhoea had abnormally high pressure indices (P less than 0.001). Pressure
      indices in all other patient groups were within the normal range. We conclude
      that gastric adaptive relaxation remains abnormal in patients with postvagotomy
      diarrhoea but not in those who are asymptomatic or who have other symptoms.

PMID- 1998860
TI  - Evaluation of the results of oesophagectomy for oesophageal cancer.
AB  - The long-term results of standard techniques of oesophagectomy were examined in
      127 patients with squamous cell carcinoma of the oesophagus. A near-total
      oesophagectomy with a cervical anastomosis was performed in 93 patients and an
      oesophagogastrectomy with an intrathoracic anastomosis was carried out in 34
      patients. One hundred and eight patients had a curative oesophagectomy and 19
      patients had a palliative resection. Eight patients received radiotherapy to the
      tumour bed. There were 15 deaths in hospital and the overall 5-year survival rate
      including perioperative deaths was 13.2 per cent. Survival was adversely affected
      by incomplete excision of macroscopic tumour (P less than 0.001), positive
      regional lymph nodes (P less than 0.05) and distant lymphatic metastases (P less
      than 0.02). The 5-year survival rate of patients with tumour invasion beyond the
      oesophageal wall (T3) and negative nodes was 20 per cent. Postoperative
      irradiation had no effect on the survival of patients with gross residual tumour.
      Complete clearance of microscopic tumour was achieved in 50 per cent of patients
      with T3 tumours and this group did not benefit from adjuvant radiotherapy.
      Survival in patients undergoing curative oesophagectomy with residual microscopic
      tumour, however, was significantly improved by irradiation of the tumour bed (P
      less than 0.01). These results suggest that the survival of patients can be
      increased significantly by the excision of all gross tumour and by identification
      of those who will benefit from local radiotherapy.

PMID- 1998861
TI  - Use of vascular staplers in major hepatic resections.

PMID- 1998862
TI  - Prolonged intermittent clamping of the portal triad during hepatectomy.
AB  - From 112 consecutive hepatectomies for malignant tumours performed with
      intermittent portal triad clamping, we have retrospectively selected the 20 cases
      in which clamping exceeded 90 min. Intermittent portal clamping of prolonged
      duration was used because of abnormal liver texture in 13 cases (mainly patients
      who had received intra-arterial chemotherapy) and/or because of technically
      difficult hepatectomy. The mean(s.d.) duration of intermittent portal clamping
      was 109(18) min and in two cases it exceeded 140 min (148 and 150 min). There was
      no postoperative mortality and the rate of postoperative morbidity was 35 per
      cent. Postoperative changes in biochemical liver tests were not major and
      transient hepatic failure occurred in only one patient following subtotal
      resection of the liver. We conclude that intermittent portal clamping is a useful
      manoeuvre in partial hepatectomy when resection is difficult or prolonged, or
      when the liver parenchyma is abnormal. Such clamping may be used for longer than
      120 min without major complications.

PMID- 1998863
TI  - Detection of colorectal liver metastases using intraoperative ultrasonography.
AB  - Intraoperative ultrasonography of the liver has been carried out in 99 patients
      undergoing surgery for colorectal cancer. Palpation of the liver, preoperative
      abdominal ultrasonography and computed tomography scanning were also performed in
      all patients. Metastases were identified in 26 of the 99 patients (26 per cent).
      Intraoperative ultrasonography diagnosed more metastases than palpation,
      abdominal ultrasonography or CT scanning, identifying metastases in 24 of the 26
      patients, including six patients in whom the metastases were not detected by any
      other technique. Identification and localization of impalpable liver metastases
      is therefore possible using intraoperative ultrasonography.

PMID- 1998864
TI  - Effect of fibrin sealant on the healing colonic anastomosis in the rat.
AB  - Fibrin adhesives have been advocated as a protective seal in colonic anastomosis
      to prevent leakage. In order to assess the effect of fibrin glue sealing we
      compared the healing of sutured colonic anastomosis in the rat (group 1) with the
      addition of human-derived fibrin sealant (group 2). As a control for a possible
      reaction to foreign protein, in group 3 the sutured anastomosis was sealed with
      specially prepared rat fibrin adhesive. On days 2, 4 and 7, ten animals in each
      group were killed. Adhesion formation was scored and the in situ bursting
      pressure was measured. The collagen concentration and degradation were estimated
      by measuring hydroxyproline. Adhesion formation was significantly increased in
      groups 2 and 3 compared with the control group. On days 2 and 7 the bursting
      pressure was not different between the groups. On day 4 the bursting pressure in
      groups 2 and 3 was significantly lower than in group 1 (P less than 0.001). These
      findings correspond with the results of collagen measurements. On day 4 the
      concentration of hydroxyproline was significantly reduced in groups 2 and 3.
      Histological examination showed infiltration of neutrophilic granulocytes into
      the sealant on days 2 and 4; on day 7 the sealant had vanished. From these
      results it is concluded that fibrin sealing of the colonic anastomosis in the rat
      does not improve healing, as demonstrated by bursting pressure and hydroxyproline
      concentration. On the contrary, it seems to have a negative influence.

PMID- 1998865
TI  - Influence of methylprednisolone on the healing of intestinal anastomoses in rats.
AB  - Although steroids are generally thought to impair intestinal anastomotic healing,
      this effect has never been proven unequivocally in either clinical or
      experimental studies. We have investigated the influence of methylprednisolone
      (2.5 or 10.0 mg kg-1 day-1) given from 2 days before operation onwards, on 3-day
      old and 7-day-old ileal and colonic anastomoses in rats. Anastomotic abscesses
      occurred more frequently in the ileum, but not in the colon, after steroid
      medication. However, methylprednisolone did not lower anastomotic bursting
      pressures in either of the bowel segments. Comparison of the hydroxyproline
      content of the anastomotic segment yielded no significant difference between
      control and methylprednisolone groups in either small or large bowel. Thus,
      healing of experimental colonic anastomoses remains unaffected by short-term
      administration of this corticosteroid.

PMID- 1998866
TI  - Influence of local hyperthermia on the healing of small intestinal anastomoses in
      the rat.
AB  - Peritoneal hyperthermia may have a role in limiting serosal metastatic disease.
      When applied to the peritoneal cavity immediately after surgery, it is important
      to know the optimum temperature, and to investigate the subsequent healing of
      intestinal anastomoses. To study the first problem, local hyperthermia was
      applied to the intestinal loop of rats for 30 min. Treatment at 46.0 degrees C or
      45.0 degrees C resulted in 100 per cent and 90 per cent mortality respectively,
      but 100 per cent survival was obtained at 44.0 degrees C. To study the second
      problem rats with intestinal anastomoses were studied in three groups: group A,
      local hyperthermia (44.0 degrees C x 30 min) applied to the intestinal loop
      containing the anastomosis; group B, local hyperthermia (44.0 degrees C x 30 min)
      applied using saline supplemented with mytomycin C (10 mg/l); group C (controls)
      no thermal treatment was applied. Anastomotic healing was assessed by breaking
      strength and histological examination. On the third day after operation, the
      breaking strength of anastomoses decreased to the lowest values in each group,
      but no statistically significant differences were noted. On the seventh and 14th
      day, increased resistance to breaking developed in all three groups and was
      greatest in the thermally treated groups. Histological findings supported these
      results. Local hyperthermia up to 44.0 degrees C x 30 min had no adverse effects
      on the healing of intestinal anastomoses.

PMID- 1998867
TI  - Infrarenal abdominal aortic disease: a review of the retroperitoneal approach.
AB  - Transabdominal exposure is the most widely used surgical approach to the
      infrarenal aorta. Over the last 30 years a number of surgeons have championed the
      retroperitoneal approach for repair of abdominal aortic aneurysms and aortoiliac
      occlusive disease using a variety of incisions. Several studies attest to the
      clinical superiority of this approach over the transabdominal route and recent
      evidence demonstrates reduced physiological disturbance with this technique. The
      retroperitoneal approach is suitable for all elective operations on the abdominal
      aorta, particularly in patients with high-risk aneurysms and in selected patients
      with symptomatic and ruptured aneurysms.

PMID- 1998868
TI  - Proliferation characteristics of human colorectal carcinomas measured in vivo.
AB  - The cell proliferation kinetics of 100 human colonic and rectal adenocarcinomas
      have been studied in vivo by bromodeoxyuridine infusion and multiparameter flow
      cytometry. A total of 97 patients, three with synchronous tumours, consented to
      receive a single bolus dose of 250 mg between 2.4 and 16 h before curative or
      palliative surgery. By this method, the ploidy pattern, the total and aneuploid
      labelling indices (LI), the S phase duration (Ts) and the potential doubling time
      (Tpot) can be estimated. Of the tumours 48 were diploid and 52 were aneuploid.
      The mean and median total LI of 100 tumours were 9.0 per cent (range 0.7-22.2 per
      cent). The mean aneuploid LI was 12.1 per cent (median 12.0 per cent, range 2.0
      25.5 per cent), and was significantly higher than the total LI (P = 0.01). The
      labelling index alone is not a sufficient indicator of proliferation, because the
      Ts also varies within and between tumours. The intertumour range of the Ts varied
      from 4.0 to 28.6 h. The mean was 14.1 h and the median was 13.1 h. The mean Tpot
      was 5.9 days (median 3.9 days) with a range of 1.7-21.4 days. No correlation was
      found between any kinetic parameters and the Dukes' classification or
      histological classification. The correlation between proliferation and prognosis
      will be established in due course.

PMID- 1998869
TI  - Correlation between laboratory findings and clinical outcome after restorative
      proctocolectomy: serial studies in 20 patients with end-to-end pouch-anal
      anastomosis.
AB  - Clinical function and anorectal physiological function were assessed and
      correlated in 20 patients with ulcerative colitis before restorative
      proctocolectomy and 3, 7, and 12 months after operation. The entire anal
      sphincter was preserved by means of a stapled pouch-anal anastomosis. Before
      operation, the median resting anal pressure was 79 cmH2O (interquartile range 70
      89 cmH2O), the rectoanal inhibitory reflex was present in all patients and
      anorectal 'sampling' was noted in 16 of 20 patients. Three months after
      operation, resting anal pressure was 68 cmH2O (range 50-87 cmH2O) (P less than
      0.001), the reflex was present in only three patients (P less than 0.001) and
      sampling was observed in one patient. After 7 months, resting anal pressure was
      76 cmH2O (range 64-89 cmH2O), the reflex was present in 11 patients and sampling
      was observed in nine patients. At 12 months, resting anal pressure was 84 cmH2O
      (range 66-94 cmH2O), the reflex was present in 19 patients and sampling was
      observed in 17 patients. The compliance and capacity of the reservoir increased
      significantly. Ability to discriminate flatus from faeces was associated with
      return of the rectoanal reflex and sampling.

PMID- 1998870
TI  - Stools containing altered blood-plasma urea: creatinine ratio as a simple test
      for the source of bleeding.
AB  - The plasma urea:creatinine ratio (U:C ratio) is known to be elevated in cases of
      upper gastrointestinal bleeding. Almost all patients with haematemesis have upper
      gastrointestinal (or generalized) bleeding so that in this study we characterized
      the diagnostic power of the U:C ratio in patients with stools containing altered
      blood without haematemesis in the hope that this simple laboratory test (used in
      conjunction, perhaps, with clinical data) might reduce the number of patients
      subjected to an unrewarding gastroscopy or colonoscopy. Of 76 cases seen in a
      provincial and a metropolitan hospital, 42 and 34 patients had upper and lower
      gastrointestinal bleeding, respectively. Fifty-four per cent of those with upper
      gastrointestinal bleeding and none of those with lower gastrointestinal bleeding
      had U:C ratios above 110 on admission. However, a discriminating level of 90 is
      considered to be more suitable, judged by the quadratic uncertainty score. At
      this level the odds for upper gastrointestinal bleeding were 15:1.

PMID- 1998871
TI  - Changes in anal canal sensation after childbirth.
AB  - Obstetic trauma predisposes to faecal incontinence. Anal canal sensation is
      impaired in incontinent patients. To assess the effect of childbirth on anal
      canal sensation anal mucosal electrosensitivity was measured in 122 primiparous
      patients in the immediate postnatal period and in 74 at 6 months postpartum.
      There were 35 normal vaginal deliveries, 36 forceps deliveries, 20 ventouse
      extractions, ten vaginal breech deliveries and 21 caesarean sections. Sensation
      was impaired in the lower, mid and upper anal canal immediately after delivery in
      those patients who had a normal vaginal delivery or a forceps delivery when
      compared with controls or with those delivered by caesarean section. Women who
      had ventouse deliveries had impaired sensation immediately after delivery in the
      mid anal canal compared with controls and those undergoing caesarean section. By
      6 months there were no differences between any group. Patients who sustained a
      division of the external anal sphincter at delivery had impaired sensation which
      persisted in the upper anal canal at 6 months.

PMID- 1998872
TI  - Neonatal small bowel atresia, stenosis and segmental dilatation.
AB  - In 8 years, 44 neonates were treated for small bowel atresia, stenosis or
      segmental dilatation by one surgical team. There was a single lesion in 30
      infants and 14 had two or more sites of intestinal obstruction. Associated
      gastrointestinal abnormalities were found in 23 (52 per cent) patients. Resection
      of the atresia(s) and primary anastomosis were performed in 34 infants and staged
      procedures were carried out in ten patients with complicated lesions. Patients
      undergoing staged procedures had a higher complication rate than those having
      primary repair (six out of ten and 11 out of 34 respectively). The overall
      initial survival rate was 93 per cent, rising to 100 per cent in those without
      associated anomalies or prenatal complications, but more than a quarter (27 per
      cent) of survivors have long-term disabilities.

PMID- 1998873
TI  - Primary papillary carcinoma of a thyroglossal duct cyst: report of a case and
      literature review.
AB  - Thyroglossal duct cysts are the most common anomaly in thyroid development. They
      are twice as frequent as branchial cleft abnormalities and, in children, are
      second only to enlarged cervical lymph nodes as the cause of neck mass.
      Generally, duct cysts are benign, but 1 per cent of cases may be malignant. From
      the world literature, 114 cases of malignant thyroglossal cysts were available
      for review. With the addition of our own case, we discuss 115 instances of duct
      cysts. The different types of neoplasia described included thyroid papillary
      carcinoma in 81.7 per cent, mixed papillary-follicular carcinoma in 6.9 per cent,
      squamous cell carcinoma in 5.2 per cent, follicular and adenocarcinoma in 1.7 per
      cent each, and malignant struma, epidermoid carcinoma and anaplastic carcinoma in
      0.9 per cent each. Of the 115 cases surveyed, 35 thyroid glands were examined
      microscopically; of these, four (11.4 per cent) contained malignant foci. Whether
      these are primary malignancies of the thyroglossal duct cysts or metastases is
      discussed.

PMID- 1998874
TI  - Solitary thyroid nodule: a prospective evaluation of nuclear scanning and
      ultrasonography.
AB  - The aim of this study was to assess prospectively the value of thyroid nuclear
      scans and ultrasound examination in the preoperative investigation of patients
      with a solitary thyroid nodule. Total thyroid lobectomy for a solitary thyroid
      nodule was performed in 68 cases. Each patient had a thyroid isotope scan (except
      two women who were pregnant) and thyroid ultrasound examination. There were 10
      (15 per cent) malignant nodules, 11 (16 per cent) benign neoplastic nodules and
      47 (69 per cent) benign non-neoplastic nodules. All of the patients with
      malignant nodules who were scanned had a solitary cold nodule on thyroid scan, as
      did 40 (69 per cent) of those with benign solitary nodules. Ultrasound
      examination of the thyroid suggested correctly that one of 16 (6 per cent) cystic
      lesions, four of 16 (25 per cent) complex solid-cystic lesions and three of 18
      (17 per cent) of solid lesions were malignant. One lesion reported as
      multinodular on ultrasonography and one reported as normal also turned out to be
      malignant. Thyroid isotope scans and ultrasound do not accurately differentiate
      between benign and malignant conditions and their routine use in the
      investigation of a solitary thyroid nodule should be abandoned.

PMID- 1998875
TI  - DNA aneuploidy in follicular thyroid neoplasia.
AB  - The potential value of DNA aneuploidy, in distinguishing benign from malignant
      follicular thyroid neoplasms, was studied. The nuclear DNA content of 65
      follicular thyroid neoplasms (52 adenomas and 13 carcinomas) was determined by
      flow cytometric analysis of paraffin embedded material; in 58 cases preparations
      were technically satisfactory. In 22 follicular neoplasms DNA analysis was also
      performed on fresh material obtained by fine needle aspiration of surgical
      specimens. Cell cycle analysis was performed on both fresh and fixed specimens.
      An aneuploid DNA profile was found on analysis of fixed tissue in eight of 45 (18
      per cent) follicular adenomas and four of 13 (31 per cent) follicular carcinomas.
      DNA aneuploidy was also found in six of the 22 (27 per cent) fresh preparations
      from follicular adenomas. The frequency of DNA aneuploidy in apparently benign
      and malignant follicular neoplasms was similar. Follicular thyroid neoplasia are
      best regarded as a single entity with a low incidence of local and distant
      spread. All follicular neoplasia are therefore best excised.

PMID- 1998876
TI  - Further evaluation of radical surgery following radiotherapy for advanced parotid
      carcinoma.
AB  - A series of 30 patients who have been treated for advanced carcinoma of the
      parotid gland using radiotherapy followed by radical surgery is presented. Three
      patients deteriorated during preoperative radiotherapy and remained unfit for
      surgery; the remaining 27 underwent radical parotidectomy with block dissection
      of the neck. Twelve patients received additional radiotherapy after operation. Of
      those patients undergoing surgery, three have been lost to follow-up, 17 have
      died and seven remain alive; the period of follow-up ranges from 3 to 133 months.
      Fourteen patients remained free of recurrent disease at death or when last seen,
      and six patients developed a local recurrence at a medium period of 10.5 (range 3
      36) months after surgery. For all 30 patients, the cumulative proportion
      surviving for 5 years was 30 per cent.

PMID- 1998877
TI  - The neck-eye reflex in patients with reduced vestibular and optokinetic function.
AB  - It is accepted that the neck-eye loop (cervico-ocular reflex, COR) is enhanced
      following loss of vestibular function and that this helps to restore gaze
      stability during head movements. In this paper we address the question of which
      structures and/or mechanisms may participate in such plastic enhancement by
      investigating the COR in 2 patients with absent vestibular function and reduced
      smooth pursuit-optokinetic eye movements (SP-OKN). The patients had multisystem
      atrophy involving the vestibular system and the cerebellum. The COR (elicited by
      angular motion of the trunk relative to the fixed head and angular motion of the
      head relative to the fixed trunk) was not enhanced in these 2 patients when
      compared with normal subjects, in contrast to previous findings in a group of
      patients with absent vestibular function alone. Measurements of slow phase eye
      movement velocity during SP-OKN stimuli and during combined COR-OKN stimulation
      (head oscillation relative to the stationary trunk in the light) showed identical
      values in these two conditions, which indicates that the neck-eye loop did not
      contribute to gaze stability during head movements. The absence of plastic
      enhancement of the COR in these patients may be secondary to interruption of SP
      OKN pathways at various possible sites and/or to involvement of the
      vestibulocerebellum, which is known to mediate adaptive plasticity in the
      vestibulo-ocular reflex.

PMID- 1998878
TI  - Frontal dysfunction and memory deficits in the alcoholic Korsakoff syndrome and
      Alzheimer-type dementia.
AB  - This study investigated the intercorrelation of 8 'frontal' tests in 32 patients
      with Korsakoff's syndrome and Alzheimer's disease, and examined the relationship
      of frontal dysfunction to impaired release from proactive interference and
      impoverished retrieval from retrograde memory. Amongst the frontal tests, there
      were statistically significant intercorrelations between 3 'fluency' tests and 3
      'card-sorting' tests, although the degree of shared variance was relatively low.
      The relationship of another test--picture arrangement errors--was more equivocal;
      performance for 'cognitive estimates' was unrelated to performance in the other
      frontal tests, possibly because it may reflect pathology at a different frontal
      site. There was no evidence in this study that variability in release from
      proactive interference was related to measures of frontal function in either
      patient group, and the conditions under which these patient groups fail to show
      'normal' release appear to be tightly constrained. On the other hand, the
      defective retrieval of retrograde memories was correlated with frontal
      dysfunction in both patient groups. There was a suggestion of a double
      dissociation with a measure of nonverbal short-term forgetting, impairment at
      which was related to the degree of general cortical atrophy rather than frontal
      dysfunction. A stepwise regression equation based on 3 frontal tests could
      account for 64% of the variability in retrograde memory performance within the
      total patient group, 68.5% in the Korsakoff group and 57% in the Alzheimer group.
      By comparison, the severity of anterograde memory impairment predicted only 21%
      of the variance in retrograde memory performance. It is concluded that frontal
      dysfunction produces a disorganization of retrieval processes which contributes
      to the temporally-extensive retrograde amnesia of these two disorders.

PMID- 1998879
TI  - Neuroacanthocytosis. A clinical, haematological and pathological study of 19
      cases.
AB  - Nineteen cases are described, including 12 cases from three different families
      and 7 nonfamilial cases, in which multisystem neurological disease was associated
      with acanthocytosis in peripheral blood and normal plasma lipoproteins. Mild
      acanthocytosis can easily be overlooked, and scanning electron microscopy may be
      helpful. Some neurologically asymptomatic relatives with significant
      acanthocytosis were identified during family screening, including some who were
      clinically affected. The mean age of onset was 32 (range 8-62) yrs and the
      clinical course was usually progressive but there was marked phenotypic
      variation. Cognitive impairment, psychiatric features and organic personality
      change occurred in over half the cases, and more than one-third had seizures.
      Orofaciolingual involuntary movements and pseudobulbar disturbance commonly
      caused dysphagia and dysarthria that was sometimes severe, but biting of the lips
      or tongue was rarely seen. Chorea was seen in almost all symptomatic cases but
      dystonia, tics, involuntary vocalizations and akinetic-rigid features also
      occurred. Two cases had no movement disorder at all. Computerized tomography
      often demonstrated cerebral atrophy. Caudate atrophy was seen less commonly, and
      nonspecific focal and symmetric signal abnormalities from the caudate or
      lentiform nuclei were seen by magnetic resonance imaging in 3 out of 4 cases.
      Depression or absence of tendon reflexes was noted in 13 cases and
      neurophysiological abnormalities often indicated an axonal neuropathy. Sural
      nerve biopsies from 3 cases showed evidence of a chronic axonal neuropathy with
      prominent regenerative activity, predominantly affecting the large diameter
      myelinated fibres. Serum creatine kinase activity was increased in 11 cases but
      without clinical evidence of a myopathy. Postmortem neuropathological examination
      in 1 case revealed extensive neuronal loss and gliosis affecting the corpus
      striatum, pallidum, and the substantia nigra, especially the pars reticulata. The
      cerebral cortex appeared spared and the spinal cord showed no evidence of
      anterior horn cell loss. Two examples of the McLeod phenotype, an X-linked
      abnormality of expression of Kell blood group antigens, were identified in a
      single family and included 1 female. The genetics of neuroacanthocytosis are
      unclear and probably heterogeneous, but the available pedigree data and the
      association with the McLeod phenotype suggest that there may be a locus for this
      disorder on the short arm of the X chromosome.

PMID- 1998880
TI  - Idiopathic intracranial hypertension. A prospective study of 50 patients.
AB  - Management of patients with idiopathic intracranial hypertension (IIH) should be
      based on the presence and progression of visual loss. To characterize the
      clinical course of IIH more completely, we monitored the clinical status,
      especially visual function, in 50 consecutive newly-diagnosed patients over a
      period of 2 to 39 months (average follow-up 12.4 months). The mean age at onset
      of symptoms was 31 (range 11-58) yrs; 46 (92%) were women and 47 (94%) were obese
      (mean weight 90 kg). Common symptoms were headache (92%), transient visual
      obscurations (72%) and intracranial noises (60%); 13 of the patients (26%)
      initially had complaints of sustained visual loss. There was visual loss as
      determined by Goldmann perimetry in 96% and by automated perimetry in 92%.
      Contrast sensitivity testing was abnormal in 50% and Snellen acuity in 22%. Two
      patients (4%) became blind in both eyes. The Goldmann visual field grade improved
      in 60% of patients but visual function deteriorated in 5 (10%). Deterioration of
      visual field grade was significantly associated only with weight gain during the
      year before diagnosis. Visual loss in patients with IIH is common and is often
      reversible. Patients should be evaluated by perimetry using an appropriate
      strategy and contrast sensitivity testing, along with careful examination of the
      optic discs.

PMID- 1998881
TI  - Intrathecal immunoglobulin M synthesis in multiple sclerosis. Relationship with
      clinical and cerebrospinal fluid parameters.
AB  - Intrathecal IgM synthesis was assessed through the detection of oligoclonal bands
      in cerebrospinal fluid (CSF) and through calculation of IgM index values and
      total CSF IgM amounts. Intrathecal production of IgM was then evaluated along
      with other CSF parameters and clinical variables in 150 patients with multiple
      sclerosis (MS). Intrathecal production of IgM was detected in 55% of patients and
      was found to correlate with disease activity, manifesting as a recent relapse, as
      well as the total number of relapses. An inverse correlation was found between
      CSF oligoclonal IgM and both the time interval between the last relapse and
      lumbar puncture, and duration of the disease process. It also correlated with the
      number of leucocytes, free kappa and lambda light chain bands in CSF. No
      correlation was found between intrathecal IgM synthesis and degree of disability
      (Kurtzke scale), disease progression index (Poser scale), or total cerebral
      plaque burden (detected by enhanced CT and MRI scans). Oligoclonal IgM bands were
      found to be more specific for active disease process than either IgM index or
      total CSF IgM amount. It is concluded that intrathecal synthesis of IgM, as
      detected by CSF oligoclonal bands, is a useful parameter in monitoring disease
      relapse activity in MS.

PMID- 1998882
TI  - Axial myoclonus of propriospinal origin.
AB  - Three patients are described with nonrhythmic repetitive axial myoclonic jerks
      causing symmetric flexion of the neck, trunk, hips and knees. No
      electrophysiological evidence of a cortical or brainstem reticular origin for the
      myoclonus was found. In the first patient the axial jerks only occurred
      spontaneously. The latencies of recruitment of spinal segments during a jerk
      indicated that the discharge arose in the mid thoracic cord and then slowly
      spread at about 5 ms-1 up and down the cord to involve rostral and caudal
      segments. No structural lesion was identified in this patient. In the second
      patient spontaneous and reflex axial jerks developed following the excision of a
      cervical haemangioblastoma. In the stimulus-induced jerks the relative latencies
      of muscles innervated by rostral and caudal spinal segments suggested that the
      myoclonus originated between the upper cervical and midthoracic cord. In the
      final patient, EMG activity during spontaneous and stimulus-induced jerks
      commenced in the rectus abdominis, and was followed by later activity in muscles
      innervated by rostral spinal segments, suggesting that the myoclonus originated
      in the midthoracic cord. No structural lesion was identified in this patient.
      Electrophysiological evidence is used to argue a spinal origin for these axial
      jerks in all 3 cases. There are striking features common both to this form of
      human myoclonus and to long propriospinal pathways identified in animals. The new
      concept of propriospinal myoclonus is suggested.

PMID- 1998883
TI  - Dual task performance and processing resources in normal subjects and patients
      with Parkinson's disease.
AB  - In recent years, there has been a growing consensus among investigators that the
      presence or absence of external cues guiding behaviour and attention is an
      important factor in determining whether or not deficits are found in patients
      with Parkinson's disease (PD). In an earlier study, the authors suggested that
      the pattern of impaired and intact performance could be explained in terms of
      differential resource demands of the tasks, combined with depleted levels of
      central processing resources in PD patients. Two experiments are reported, both
      employing dual-task paradigms. The first assessed, in normal subjects, the
      relative processing demands of a cued and an uncued version of the Stroop task.
      The results supported the proposal that the noncued task made greater demands on
      the subject's limited processing resources. Further, performing a resource
      demanding secondary task concurrently with the Stroop test produced, in normal
      subjects, the same pattern of impaired performance as that reported previously in
      PD patients. In the second experiment the same dual-task paradigm was employed
      with a group of PD patients and normal aged-matched controls. Only the patients
      showed an increase in reaction time on the Stroop task when performing a resource
      demanding secondary task. The patients also showed an interfering effect with
      concurrent foot tapping but not with an articulatory suppression task. The
      results were taken to support the hypothesis that PD patients have depleted
      central processing resources. In considering the present data, alternative
      explanations for the results are considered, in particular the possibility that
      they represent a deficit in switching processing resources between two tasks as
      the combined demands outweigh available resources.

PMID- 1998884
TI  - The mechanism of spastic muscle hypertonus. Variation in reflex gain over the
      time course of spasticity.
AB  - The electromyographic (EMG) response of the initially passive biceps brachii
      muscle to imposed extension applied at the elbow was studied in 19 hemiparetic
      and 12 normal subjects. In relaxed normal subjects, the biceps muscle was found
      to respond only at displacement velocities above 175 deg/s, with a single early
      burst of activity in the biceps EMG. In contrast, the hemiparetic subjects, in
      addition to the early EMG activity, also showed considerable late activity, which
      persisted even with stretch velocities as low as 35 deg/s. This late activity is
      a stretch reflex, present in fully plegic arms. It was seen in all spastic
      subjects in whom the tone of the biceps had been clinically assessed to be
      raised, but was never observed in subjects with normal muscle tone. The mean
      level of this EMG response was highly correlated with displacement velocity and
      its duration to the duration of the applied displacement. It is suggested that
      this reflex EMG activity is the major factor in the genesis of spastic hypertonus
      in the arm and that it arises not from a reduction in the threshold of the
      stretch reflexes of the muscle, but from a pathological increase in stretch
      reflex gain. It is further shown that this activity is at a high level between
      the first and third months after the onset of spasticity and that the reflex gain
      is significantly reduced when spasticity is established for a year or more. It is
      concluded that, while changes in passive mechanical properties may play a role
      when spasticity has been established for more than a year, the major cause of
      spastic muscle hypertonus is a pathological increase in stretch reflex activity.

PMID- 1998885
TI  - Reversed lateralization of cognitive functions in right handers. Exceptions to
      classical aphasiology.
AB  - Most current and past research on the cerebral organization of cognitive
      functions has presupposed certain specialized hemisphere operations. At least for
      right handers, language and praxis are to be organized in the left hemisphere,
      while affective prosody, configurational spatial capacity, and global attention
      are lateralized in the right hemisphere. Deviations from these presuppositions,
      as in crossed aphasics and perhaps left handers, are generally considered to be
      'exceptions' and either to disprove the rules or to be irrelevant to the rule. We
      report 4 very 'exceptional' cases, right handers with almost entirely reversed
      lateralization of functions. Analysis of the intrahemispheric relationships
      between functions suggests that there may be a specific neurobiology to the
      interrelationships between and among cognitive functions, handedness, and the
      intrahemisphere localization of the function.

PMID- 1998886
TI  - Short-term memory and sentence comprehension. An investigation of a patient with
      crossed aphasia.
AB  - The relationship between short-term memory impairment and sentence comprehension
      is explored in a right-handed patient with a focal temporoparietal lesion of the
      right hemisphere. The general clinical profile, as well as characteristics of the
      patient's immediate memory for word lists, suggests the occurrence of a 'mirror
      image' crossed aphasia. Detailed analysis of the patient's ability to repeat and
      to comprehend sentences, however, indicates some important differences between
      this case and previously reported patients with short-term memory impairment. It
      is suggested that these differences, which may be related to an unusual pattern
      of neuroanatomical organization of cognitive functions, involve symptom
      dissociations with implications for models of normal language/memory
      interactions.

PMID- 1998887
TI  - Maintenance of myelinated fibre g ratio in acute experimental allergic
      encephalomyelitis.
AB  - The spectra of myelin sheath thickness and g ratio (axon diameter/fibre diameter)
      of guinea pig optic nerves for 8 animals with acute experimental allergic
      encephalomyelitis (EAE) were compared with those for 6 normal animals. The mean
      myelin sheath thickness of 0.12 microns for the animals with EAE was
      significantly lower than the value of 0.16 microns for the normal animals. Since
      fibre diameter comprises axon diameter plus the thickness of its surrounding
      myelin sheath, a reduction in mean fibre diameter from 1.52 microns in normals to
      1.20 microns in EAE was expected, but it was surprising to find that a mean g
      ratio of 0.85 obtained for normal nerves was not substantially different from a
      value of 0.86 for demyelinated optic nerves. A decrease in the mean axon diameter
      of 1.24 microns for normal animals to 0.94 microns for those with EAE tended to
      offset the decrease in mean myelin sheath thickness and contributed to the
      relative stability of the g ratio with acute demyelination. Our results showing
      reduction in axonal calibre and myelin sheath thickness may offer an explanation
      for apparent discrepancies between electrophysiological delays in conduction
      characteristics of experimental and, if not the result of a maturational effect
      on myelination, human primary demyelinating disorders associated with the scant
      histopathological demyelination of initial attacks of EAE and the visually
      asymptomatic patients with multiple sclerosis.

PMID- 1998888
TI  - Memory-contingent saccades and the substantia nigra postulate for essential
      blepharospasm.
AB  - Essential blepharospasm and cranial dystonia are related focal dystonias of
      unknown aetiology. Blepharospasm induced by acute dopamine depletion in
      parkinsonism restricts saccade initiation possibly via the substantia nigra pars
      reticulata (SNpr). If essential blepharospasm and cranial dystonia similarly
      restrict saccades, then a selective, somatotopically arranged pathway such as the
      SNpr may be involved. To test this possibility memory-contingent and visually
      guided saccades were measured in patients with essential blepharospasm and
      cranial dystonia. The latency of both forms of saccades was either significantly
      prolonged or excessively variable, while the accuracy and peak velocity of these
      fast eye movements were similar to age-matched control subjects. Essential
      blepharospasm and cranial dystonia alter the initiation of saccadic eye
      movements. Subcortical brain regions or pathways where eyelid, saccade and
      cranial/cervical motor control are somatotopically approximated, such as the
      SNpr, may be involved in blepharospasm.

PMID- 1998889
TI  - Task-dependent variations in parkinsonian motor impairments.
AB  - Studies of visually-guided arm movements in patients with Parkinson's disease
      (PD) have suggested a relationship between slowness of movement and a reduction
      in the ratio of movement amplitude and peak velocity. Recent studies indicate,
      however, that PD impairments may be different for well-learned, natural movements
      performed without visual guidance, or movements associated with sequential motor
      behaviours such as speech. To address this issue, PD subjects and age/sex-matched
      controls were compared on the performance of three tasks, all of which required
      lowering the jaw: (1) single, rapid, visually-guided movements; (2) equivalent
      movements associated with a single speech syllable (inherently without visual
      guidance), and (3) well-learned speech movements produced in a natural sequence.
      PD subjects manifested similar deficits for visually-guided jaw lowering as those
      previously reported for arm movements, namely reduced velocity/amplitude ratios
      and increased movement durations. By contrast, analogous jaw movements during the
      sequential speech tasks were unimpaired on these measures. These results suggest
      that PD motor impairments are influenced by a variety of factors, including the
      degree to which tasks are familiar and natural, and the availability of visual
      information.

PMID- 1998890
TI  - The stroke syndrome of striatocapsular infarction.
AB  - Striatocapsular infarction has recently been described as a distinct stroke
      entity and forms an important subgroup of subcortical infarctions. In a
      prospective study of 50 consecutive patients over a 10 yr period with this
      syndrome, clinical and neuropsychological features, pathogenesis and outcome were
      studied to provide information concerning management and prognosis. The most
      common clinical presentation was that of a stroke affecting mainly the upper limb
      with cortical signs such as dysphasia, neglect or dyspraxia. Evidence from EEG,
      angiographic and neuropsychological data supported a vascular/haemodynamic basis
      for the presence of the acute neuropsychological changes, while the chronic
      changes were more likely to be due to diaschisis. A study of risk factors and
      cerebral angiography enabled 4 pathophysiological subgroups to be identified: (1)
      cardiac emboli to the origin of the middle cerebral artery; (2) severe extra
      cranial cranial carotid artery occlusive disease with presumed embolism to the
      same site and/or involvement of haemodynamic factors; (3) proximal middle
      cerebral artery abnormalities causing occlusion of multiple lateral striate
      arteries at their origins; (4) normal angiography where pathogenesis was
      uncertain. The risk factors of cardiac disease and smoking were significantly
      increased as compared with age and sex-matched controls with other forms of
      ischaemic stroke. Stroke or vascular death rate was 2.7% per yr during a mean
      follow-up period of 2.25 yrs. Predictors of an excellent recovery with return to
      normal lifestyle were younger age, only brachial or brachiofacial weakness with
      absence of cortical signs at presentation and minimal change on angiography. This
      stroke entity deserves particular recognition in the spectrum of subcortical
      infarctions because of its specific pathogenesis, distinct neuropsychological
      features and reasonable prognosis.

PMID- 1998891
TI  - Human olfactory discrimination after unilateral frontal or temporal lobectomy.
AB  - Olfactory discrimination and detection was studied in 106 patients with
      unilateral cerebral excision in the right or left temporal lobe, right or left
      frontal lobe, left parietal lobe, or right frontal and temporal lobes, and in 20
      normal control subjects. Detection thresholds for n-butyl alcohol, measured
      separately in each nostril, did not differ across subject groups or across
      nostrils, thus excluding any primary sensory loss. The discrimination task
      involved monorhinal presentation of repairs of unfamiliar odorants, which the
      subjects judged as same or different in quality. The results showed a significant
      deficit in discrimination confined to the nostril ipsilateral to the lesion in
      patients with temporal lobe removals. Patients with frontal lobe excisions were
      also impaired and, for patients with right frontal lesions including the orbital
      cortex, the impairment was found in both nostrils. Patients with left parietal
      lesions did not demonstrate any significant deficits. Normal subjects showed
      consistently better performance in the right than in the left nostril. The
      results are interpreted as reflecting the importance of the orbitofrontal cortex
      in olfactory discrimination. Temporal lobe lesions may disrupt the input to the
      orbitofrontal cortex, thereby producing poorer performance. The nostril
      difference in the normal subjects, together with the birhinal impairment in
      patients with right orbitofrontal damage, suggest a relative advantage of the
      right orbital region in olfactory processing.

PMID- 1998892
TI  - Muscle performance, voluntary activation, twitch properties and perceived effort
      in normal subjects and patients with the chronic fatigue syndrome.
AB  - The decrease in maximal force-generating capacity, the degree of central
      activation of the muscle, and the subjective perception of effort were measured
      during prolonged submaximal isometric exercise in 12 male patients suffering from
      the 'chronic fatigue syndrome' and 13 naive, healthy male subjects. Maximal
      voluntary isometric torque generated by the elbow flexors was measured before,
      and at 5 min intervals during an endurance sequence of 45 min of repetitive
      isometric contractions (6 s duration, 4 s rest interval) producing 30% of the
      initial maximal voluntary torque. Electrical stimuli were also delivered to the
      elbow flexors to measure the contractile force in the intervals between voluntary
      contractions. The degree of central motor activation during maximal voluntary
      contractions was assessed using a sensitive method of twitch interpolation. In
      addition, the perceived effort required to achieve the target submaximal
      contractions was recorded using a standardized self-report scale. A high degree
      of central activation was achieved in maximal contractions during the endurance
      sequence both in the patients (mean of maximal force 93.6%; SD 7.8%), and in the
      control subjects (mean 90.9%; SD 9.5%). The relative torque produced by either
      voluntary or electrically stimulated contractions was not significantly different
      between patients and control subjects throughout the test. There was no
      significant difference in the perceived exertion between the patients and control
      subjects. These findings support the concept that neither poor motivation, nor
      muscle contractile failure is important in the pathogenesis of 'fatigue' in
      patients with the chronic fatigue syndrome.

PMID- 1998893
TI  - Sequencing in Parkinson's disease. Abnormalities in programming and controlling
      movement.
AB  - Central programming deficits in Parkinson's disease (PD) were studied in two
      reaction time (RT) experiments. In Experiment 1, PD patients and controls
      performed sequences of hand postures that varied in length, the number of
      different postures (repetitive vs heterogeneous), and the delay interval before
      movement. Before movement, the PD group planned repetitive movements like
      controls whereas for heterogeneous sequences RT increased less with sequence
      length for the PD group, implying less preprogramming. The interresponse time
      (IRT) data from repetitive sequences showed that the PD group had difficulty
      controlling movement such that IRTs were faster when sequences were longer, thus
      allowing more time to schedule the termination of the sequence during the course
      of movement. For heterogeneous sequences, the PD group made more errors and were
      slower than controls when changing hand postures, suggesting a deficit in
      switching between different responses. While RT decreased with a longer delay
      similarly for both groups, IRT1 continued to improve only for the PD group but
      similarly for both types of sequences, suggesting a deficit specific to
      programming the first response. In Experiment 2, subjects made decisions about
      the number of different hand postures contained within a sequence. PD patients'
      decision times improved more with a longer delay only for heterogeneous
      sequences, suggesting a problem in identifying the number of different hand
      postures. The results have implications for levels of motor dysfunction in PD
      which emphasize the influence of sequence length and complexity.

PMID- 1998894
TI  - Chemical and biologic warfare.

PMID- 1998895
TI  - The national AIDS strategy is a start, nothing more.

PMID- 1998896
TI  - Stop wasting health care dollars on dying seniors, physician says.

PMID- 1998897
TI  - Quinine or quinidine?

PMID- 1998898
TI  - Dr. Maude Abbott deserves better.

PMID- 1998899
TI  - Is there a doctor in the court?

PMID- 1998900
TI  - We could learn a lesson from Kenya's midwives.

PMID- 1998901
TI  - Asbestos: the turbulent interface between science and policy.

PMID- 1998902
TI  - Preparing faculty to teach in a problem-based learning curriculum: the Sherbrooke
      experience.
AB  - Over the last 6 years Sherbrooke Medical School has undertaken a major reform of
      its undergraduate curriculum. A new student-centred, community-oriented
      curriculum was implemented in September 1987. Problem-based learning (PBL) is now
      the main educational method. To adequately prepare teachers for the curriculum a
      series of faculty development programs in pedagogy were offered: first, a 2-day
      introductory workshop to initiate teachers into educational principles and their
      application in the new program; second, a 1-year basic training program in
      medical pedagogy; third, a 1-day workshop on PBL; and fourth, a comprehensive 3
      day training program in PBL tutoring. Over 60% of all full-time teachers attended
      the introductory program and 80% the tutor training program. The 1-year basic
      training program was completed by 33% of the faculty members. The implementation
      of these programs, coupled with a high participation rate, resulted in a more
      student-centred educational philosophy and a greater interest in medical
      education. This had a significant impact when the new curriculum was instituted.
      Lessons learned from the experience are discussed.

PMID- 1998904
TI  - Silicone mastopathy mimicking malignant disease of the breast in southeast Asian
      patients.

PMID- 1998903
TI  - Characteristics of pregnant women exposed to cocaine in Toronto between 1985 and
      1990.
AB  - OBJECTIVE: To determine the characteristics of pregnant women exposed to cocaine.
      DESIGN: Case-control study. SETTING: Women attending the Motherisk Program,
      Hospital for Sick Children, Toronto, from September 1985 to March 1990. PATIENTS:
      All women who had admitted using cocaine before or during pregnancy. Of the two
      control groups the first comprised women who had admitted using cannabinoids but
      not cocaine before or during pregnancy and the second those who attended the
      clinic just before the cocaine case but who had not used illicit drugs. OUTCOME
      MEASURES: Age, marital status, ethnic background, number of pregnancies, children
      and elective or spontaneous abortions, socioeconomic status of woman and male
      partner, alcohol use, cigarette use, frequency of cocaine use and total amount
      taken. MAIN RESULTS: Of the 1625 women 91 (5.6%) admitted to using cocaine: 86
      during the current pregnancy, 3 before the current pregnancy, 1 before planning a
      pregnancy and 1 during a previous pregnancy. None of the cocaine users were
      considered to be addicts; only 20% had used the drug more than 10 times. A total
      of 74 women used cannabinoids only. The mean age of the cocaine users was 27.1
      (standard deviation [SD] 5.3) years; this was significantly lower than that of
      the control subjects (30.5 [SD 5.2] years) (p less than 0.001). More of the
      cocaine users than of the women in either of the two control groups were single
      (60% v. 38% and 14%, p less than 0.001). The cannabinoid users had significantly
      higher parity and the nonusers a significantly lower incidence of elective
      abortions than the cocaine users. The cocaine users had a significantly lower
      socioeconomic status than the control subjects (p less than 0.001); similarly,
      the male partners of the cocaine users had a significantly lower socioeconomic
      status than the partners of the control subjects (p = 0.001). CONCLUSIONS:
      Pregnant cocaine users who seek drug counselling represent a unique risk group,
      with clustering of factors such as alcohol and cigarette use and low
      socioeconomic status that compound the risk to the fetus. New strategies should
      be explored to identify such women, especially addicts, in their communities and
      to urge them to seek counselling and treatment.

PMID- 1998905
TI  - Dietary fat and cancer.

PMID- 1998906
TI  - Dr. Harold Griffith and the introduction of curare.

PMID- 1998907
TI  - Major changes in medical training planned for Queen's, CMA council told.

PMID- 1998908
TI  - False-positive results and HIV seroprevalence rates.

PMID- 1998909
TI  - HIV antibody testing: CMA counselling guidelines.

PMID- 1998910
TI  - Informed consent to HIV antibody testing.

PMID- 1998911
TI  - Smoking and health.

PMID- 1998912
TI  - Walk-in clinics: implications for family practice.

PMID- 1998913
TI  - Assessing new technology.

PMID- 1998914
TI  - ESWL: the choice of many urologists.

PMID- 1998915
TI  - Management of people exposed to pertussis and control of pertussis outbreaks.

PMID- 1998916
TI  - Abortion and the law.

PMID- 1998917
TI  - [Therapeutic abortion].

PMID- 1998918
TI  - Why are there so many injuries? Why aren't we stopping them?

PMID- 1998919
TI  - Unfair competition for charitable donations?

PMID- 1998920
TI  - Genital injuries in sexual assault victims.

PMID- 1998921
TI  - Chlorpropamide or chlorpromazine?

PMID- 1998922
TI  - Guidelines for medical practice.

PMID- 1998923
TI  - Writing prescription instructions.

PMID- 1998924
TI  - AIDS research funding in Canada: future directions and government policy.

PMID- 1998925
TI  - Clearing the air on malaria.

PMID- 1998926
TI  - Periodic health examination, 1991 update: 2. Administration of pneumococcal
      vaccine. Canadian Task Force on the Periodic Health Examination.

PMID- 1998927
TI  - Legal obligation of physicians to disclose information to patients.
AB  - Obtaining a patient's consent is a routine daily process for physicians, although
      many are unaware of the scope of this legal obligation. In 1980 the Supreme Court
      of Canada changed the law relating to informed consent; promotion of patient
      autonomy shifted the focus from a standard of professional disclosure to one of a
      "reasonable patient." Physicians have a legal obligation to disclose to patients
      specific information, the scope of which is determined by a court on the basis of
      a reasonable patient's expectation and the circumstances of the case. This gives
      rise to many controversies in the practice of clinical medicine. It is difficult
      for physicians to know which treatment risks require disclosure, since this is
      decided by a court in a retrospective analysis of the evidence. Will the court
      recognize exceptions to the duty of disclosing information? If several health
      care professionals are involved in a patient's care who has the duty to disclose
      information? Can this duty be delegated? This paper provides physicians with
      guidelines that are consistent with the promotion of patient autonomy and comply
      with the doctrine of informed consent. In addition, it suggests ways of improving
      awareness of the doctrine and procedures to ease its application.

PMID- 1998928
TI  - Clinical features and treatment of obstructive sleep apnea.
AB  - OBJECTIVE: To review the clinical features and treatment of obstructive sleep
      apnea (OSA). DATA SOURCE AND SELECTION: All articles on OSA published in French
      and English between 1970 and 1990 and indexed in Index Medicus were reviewed.
      Studies addressing the epidemiologic features and clinical aspects of OSA were
      selected, and special emphasis was given to articles reporting the effects of
      treatment on morbidity and mortality rates. MAIN RESULTS: OSA is characterized by
      episodes of upper airway obstruction during sleep that result in repetitive
      hypoxemia and sleep disruption. OSA leads to various neuropsychologic and
      cardiovascular complications, including daytime hypersomnolence, cognitive
      impairment, systemic and pulmonary hypertension and cardiac arrhythmias. There is
      suggestive evidence that the death rate among affected people is increased. The
      true incidence of OSA is unknown, but estimates have varied from 1% upwards among
      men. The current treatment with the greatest overall effectiveness and
      acceptability is nasal continuous positive airway pressure. CONCLUSION: This
      common, readily treatable disorder is associated with serious complications and
      therefore must be widely recognized by health professionals.

PMID- 1998930
TI  - Effect of educational program and interview on adoption of guidelines for the
      management of neonatal hyperbilirubinemia.
AB  - OBJECTIVES: To determine (a) whether physicians are adhering to the guidelines
      for the management of neonatal hyperbilirubinemia, (b) what influences their
      decisions to investigate and treat the condition and (c) the effect of an
      educational program and clinical recall interview on compliance with the
      guidelines. DESIGN: Retrospective chart audit. SETTING: Urban tertiary care
      hospital. PARTICIPANTS: All term neonates who received phototherapy but were not
      admitted to the neonatal intensive care unit. INTERVENTIONS: Educational program
      and clinical recall interview. MEASURES: Charts were reviewed from March to May
      1986 (period I, before publication of the guidelines) and from November 1986 to
      January 1987 (period II, after publication and after the educational program).
      The audits were repeated from April to June 1989 (period III, during the
      interview phase) and from October to December 1989 (period IV, 6 months after the
      interviews). Two criteria determined the appropriate use of phototherapy: the
      serum bilirubin level and the postnatal day on which phototherapy was started.
      RESULTS: The proportion of infants receiving phototherapy for whom there were
      orders for complete blood counts to investigate hyperbilirubinemia increased from
      20% in period I to 37% in period IV. The frequency of orders to determine the
      proportion of reticulocytes did not change significantly. The number of infants
      receiving phototherapy decreased over the study periods. The proportion receiving
      phototherapy in accordance with the criteria for the serum bilirubin level
      increased from 10% to 17% after the educational program (insignificant
      difference) and to 31% after the interviews (p = 0.02). Compliance with the
      guidelines was greater before the infants were 2 days old than when they were 3
      days old or more (p = 0.01). Of the 45 physicians who prescribed phototherapy
      (for 94 infants) during period IV 26 never prescribed in accordance with the
      guidelines. The other 19 prescribed in accordance with the guidelines for 30 of
      52 infants. Decisions to investigate and treat with phototherapy were affected by
      clinical and parental factors in addition to the guidelines. Two of the 25
      physicians interviewed stated that the interview would influence their management
      of future cases of hyperbilirubinemia. CONCLUSION: A clinical recall interview
      can have a greater impact on changing physician management practices than factual
      communication on a group basis.

PMID- 1998929
TI  - Effectiveness of a geriatric day hospital.
AB  - OBJECTIVE: To determine whether there is a difference in the quality of life
      between elderly patients managed in a day hospital and those receiving
      conventional care. DESIGN: Randomized controlled trial; assessment upon entry to
      study and at 3, 6 and 12 months afterward. SETTING: Geriatrician referral-based
      secondary care. PATIENTS: A total of 113 consecutively referred elderly patients
      with deteriorating functional status believed to have rehabilitation potential;
      55 were assessed and treated by an interdisciplinary team in a day hospital
      (treatment group), and 58 were assessed in an inpatient unit or an outpatient
      clinic or were discharged early with appropriate community services (control
      group). OUTCOME MEASURES: Barthel Index, Rand Questionnaire, Global Health
      Question and Geriatric Quality of Life Questionnaire (GQLQ). MAIN RESULTS: Eight
      study subjects and four control subjects died; the difference was insignificant.
      Functional status deteriorated over time in the two groups; although the
      difference was not significant there was less deterioration in the control group.
      The GQLQ scores indicated no significant difference between the two groups in the
      ability to perform daily living activities and in the alleviation of symptoms
      over time but did show a trend favouring the control group. The GQLQ scores did
      indicate a significant difference in favour of the control group in the effect of
      treatment on emotions (p = 0.009). CONCLUSION: The care received at the day
      hospital did not improve functional status or quality of life of elderly patients
      as compared with the otherwise excellent geriatric outpatient care.

PMID- 1998931
TI  - Diet and blood lipid levels: effect of "nibbling".

PMID- 1998932
TI  - Our unremarkable transition from peace to war.

PMID- 1998933
TI  - Soviets seek health care help for the "prisoners of Chernobyl".

PMID- 1998934
TI  - Is the "average" medical student becoming extinct?

PMID- 1998935
TI  - North of Siberia, the medical challenges are many.

PMID- 1998936
TI  - Growing number of "Jim Henson's" disease cases worries Ontario Doctors.

PMID- 1998937
TI  - Community health centres: do they pose a threat to fee-for-service medicine?

PMID- 1998938
TI  - Jehovah's Witnesses and the transfusion debate: "We are not asking for the right
      to die".

PMID- 1998939
TI  - The whole thing.

PMID- 1998940
TI  - The effects of ellagic acid and 13-cis-retinoic acid on N
      nitrosobenzylmethylamine-induced esophageal tumorigenesis in rats.
AB  - Ellagic acid (EA) and 13-cis-retinoic acid (CRA), both alone and in combination,
      were tested for their ability to inhibit N-nitrosobenzylmethylamine-induced
      tumors in the rat esophagus. Groups of male rats were fed AIN-76A diet containing
      EA (4 g/kg), CRA (240 mg/kg), or a combination of EA and CRA (4 g/kg and 240
      mg/kg), respectively, for 25 weeks. Two weeks after initiation of the diets, NBMA
      (0.5 mg/kg per injection) was administered s.c. once weekly for 15 weeks. After
      25 weeks on the diets, the animals were necropsied. The incidence of esophageal
      tumors was 97-100% in all NBMA-treated groups. The multiplicity of tumors in NBMA
      treated groups was reduced significantly by EA (60%), but not by CRA, or by EA +
      CRA. These results demonstrate that EA and CRA do not act synergistically to
      inhibit NBMA-induced esophageal tumorigenesis.

PMID- 1998942
TI  - High-dose inhibition and low-dose enhancement of murine sarcoma growth exhibited
      by BCG vaccine.
AB  - An in vivo assay for BCG anti-cancer efficacy was developed, utilizing
      subcutaneous injection into CFW Swiss-Webster mice of cultured S180 sarcoma cells
      and mixed with freeze-dried TiceTM BCG vaccine. A BCG dose of 0.156-1.56 mg dry
      weight significantly inhibited tumor formation, but a BCG dose of 0.156-1.56
      micrograms significantly enhanced tumor growth, evidenced by increased tumor
      incidence, volume and initial growth rate. These antagonistic activities may
      contribute to the high variability of BCG anti-cancer efficacy seen in animals
      and humans and indicate the need to exercise caution when employing even low
      doses of BCG for cancer immunotherapy.

PMID- 1998941
TI  - Involvement of singlet oxygen in chloroaluminum phthalocyanine tetrasulfonate
      mediated photoenhancement of lipid peroxidation in rat epidermal microsomes.
AB  - In recent studies chloroaluminum phthalocyanine tetrasulfonate (AlPCTS) has been
      shown to be an effective photosensitizer for the tumor necrosis in a modality
      known as photodynamic therapy, but the mechanism of photodynamic effect of AlPCTS
      is poorly understood. In this study, in vitro incubation of rat epidermal
      microsomes with AlPCTS followed by exposure to red light (approximately 675 nm)
      resulted in an increase in ADP/iron-supported lipid peroxidation, a measure of
      membrane damage. This photodestructive effect was found to be dependent on both
      the duration of light exposure and the dose of AlPCTS. Studies employing various
      quenchers of reactive oxygen species revealed that scavengers of singlet oxygen
      (histidine, 2,5-dimethylfuran, beta-carotene and sodium azide) afforded
      substantial protection (up to 90%) of photoenhancement whereas the scavengers of
      hydrogen peroxide (catalase), superoxide anion (superoxide dismutase), and
      hydroxyl radical (sodium benzoate, mannitol and ethanol) were ineffective in this
      regard. Our data indicate that AlPCTS-mediated photodestruction mainly involves a
      type II reaction via singlet oxygen formation and suggest that the latter could
      play a significant role in the tumor necrosis evoked by AlPCTS and light.

PMID- 1998943
TI  - Antiproliferative effects of citrus flavonoids on a human squamous cell carcinoma
      in vitro.
AB  - We examined the effects of four plant flavonoids (quercetin, taxifolin, nobiletin
      and tangeretin) on the in vitro growth of a human squamous cell carcinoma cell
      line (HTB43). Cell cultures were treated with each flavonoid (2-8 micrograms/ml)
      for 3-7 days. Cell viability, as determined by counting cells, correlated well
      with that obtained from a colorimetric assay for cellular growth utilizing 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. The polymethoxylated
      flavonoids, nobiletin and tangeretin, markedly inhibited cell growth at all
      concentrations tested on days 5 and 7. On day 3, the inhibition observed was 70
      72% at 8 micrograms/ml, while on day 5, it ranged from 61-88% at 2-4
      micrograms/ml. Quercetin and taxifolin exhibited no significant inhibition at any
      of the concentrations tested. This difference in activity may be due to the
      relatively greater membrane uptake of the polymethoxylated flavonoids since
      methoxylation of the phenolic groups decreases hydrophilicity of the flavonoid.

PMID- 1998944
TI  - Lack of carcinogenicity of 2-aminofluorene, its glucuronide and the glucuronide
      of N-hydroxy-2-acetylaminofluorene in heterotopic bladder of the rat.
AB  - The role of 2-aminofluorene and its N-glucuronide and the O-glucuronide of N
      hydroxy-2-acetylaminofluorene in the bladder carcinogenesis by 2-aminofluorene
      were investigated. These compounds were injected into heterotopically
      transplanted bladders of male rats at a weekly dose of 1 mumol for 20 weeks. The
      experiment was terminated at the end of 50 weeks. The results showed that none of
      these compounds were carcinogenic in the heterotopically transplanted bladder.
      The O-glucuronide was not carcinogenic even when it was administered in a
      phosphate saline (pH 8.0), that favors the activation of this compound. The N
      glucuronide of N-hydroxy-2-aminofluorene, a positive control, produced urothelial
      tumors. These results are consistent with the hypothesis that the N-glucuronides
      of hydroxylamines, but not the O-glucuronides of hydroxamic acids, are
      responsible for bladder carcinogenesis by arylamines.

PMID- 1998945
TI  - Increased synthesis of N1-acetylspermidine in hepatic preneoplastic nodules and
      hepatomas.
AB  - Hepatic preneoplastic nodules and hepatomas obtained in a multistep protocol of
      rat hepatocarcinogenesis (diethylnitrosamine, 2-acetylaminofluorene, and partial
      hepatectomy) showed high values of spermidine N1-acetyltransferase activity, the
      rate-limiting enzyme in polyamine interconversion. Such an increase was
      associated with the appearance of N1-acetylspermidine, an enhancement in
      putrescine, and a decline in spermine. Such changes suggest an activation of the
      interconversion pathway of high into lower polyamines in hepatic preneoplastic
      nodules and hepatomas.

PMID- 1998946
TI  - Role of dietary oleic acid in linoleic acid-enhanced metastasis of a mouse
      mammary tumor.
AB  - We have previously shown that a high fat diet (20% w/w) containing 12% linoleic
      acid (18:2) can significantly increase the metastasis of mammary tumor cells when
      compared with high fat diets that contain 8% or less 18:2 with a constant level
      of oleic acid (18:1). This effect may have been due to an alteration of
      eicosanoid metabolism because the cyclooxygenase inhibitor, indomethacin,
      abolished the increase. Because 18:1 may interfere with the metabolism of 18:2 to
      20:4, we have now tested whether the 18:1 that supplements the 18:2 diet can have
      an effect on spontaneous or experimental metastasis of the line 4526 murine
      mammary tumor. For this, six 20% fat diets were formulated with 1%, 6%, and 12%
      18:2 and either high or low levels of 18:1. Our results indicate that the amount
      of select fatty acids other than 18:2 at 12% has no significant effect on mouse
      growth, tumor growth, or tumor latency. When spontaneous metastatic burden was
      calculated, no significant differences between mice fed diets containing 1% and
      6% 18:2 were observed. However, 4 to 5 times more of a metastatic burden was
      observed in mice fed diets containing 12% 18:2. No significant differences were
      observed between high and low 18:1 diets when the 18:2 content was 1 or 12%.
      However, at 6% 18:2, 18:1 significantly decreased metastatic burden. When
      experimental metastasis was assessed, relatively low levels of surface lung
      nodules were observed at 1% and 6% 18:2, but significantly higher levels were
      observed at 12% 18:2.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1998947
TI  - Identification of membrane antigens in granulocytes and colonic carcinoma cells
      by a monoclonal antibody specific for biliary glycoprotein, a member of the
      carcinoembryonic antigen family.
AB  - The gene coding for 'biliary glycoprotein (BGP)' is a member of the
      carcinoembryonic antigen (CEA) gene family. A monoclonal antibody (MAb) was
      induced against a BGP-preparation isolated from human bile. The antibody did not
      crossreact with the carcinoembryonic antigen (CEA) and different non-specific
      crossreacting antigens. The anti-BGP MAb was used to identify BGP-related
      antigens in membrane extracts from granulocytes and the colonic carcinoma cell
      line HT-29. In granulocyte membranes, a single antigen of Mr 160,000 was bound.
      In membranes from HT-29 cells, a main antigen of Mr 85,000 was present. At high
      antigen concentration, an additional antigen of Mr 115,000 was identified. Since
      several transcripts of the BGP gene have been identified, the different BGP
      related antigens are probably products of alternatively spliced mRNAs.

PMID- 1998948
TI  - Inhibition of human renal cancer by monoclonal antibody targeted methotrexate
      containing liposomes in an ascites tumor model.
AB  - The monoclonal antibody DAL K29 against a human renal cell carcinoma associated
      cell surface antigen was covalently linked to small unilamellar lipid vesicles
      (SUV) containing the antifolate, methotrexate (MTX), with full retention of
      antibody activity. In an ascites tumor model developed after intraperitoneal
      inoculation of 5 x 10(6) cells of the human kidney cancer line Caki-1 per
      pristane primed nude mouse, the DAL K29 linked MTX-containing SUV was a more
      potent tumor inhibitor (P less than 0.0005) than the drug or MAB alone, MTX
      containing SUV, a mixture of DAL K29 and MTX-containing SUV or MTX-containing SUV
      linked to an isotype matched nontumor specific IgG.

PMID- 1998949
TI  - Low frequency of ras gene mutations in neuroblastomas, pheochromocytomas, and
      medullary thyroid cancers.
AB  - Little is known about the prevalence and significance of ras gene activation in
      neural crest tumors such as neuroblastomas, pheochromocytomas, and medullary
      thyroid cancers (MTCs). Therefore, we analyzed DNA from 10 human neuroblastoma
      cell lines and 10 primary human pheochromocytomas for activating mutations in N
      ras, H-ras, and K-ras. We also studied DNA from 24 primary neuroblastomas and 10
      MTCs for N-ras mutations. ras genes were analyzed by direct sequencing of
      specific DNA fragments amplified by the polymerase chain reaction. With the
      exception of the SK-N-SH cell line, the examined ras gene sequences were normal
      in all the neuroblastomas, pheochromocytomas, and MTCs tested. A single point
      mutation was identified at codon 59 (GCT(ala)----ACT(thr)) in one N-ras allele in
      an SK-N-SH subline. Interestingly, this mutation is different from the activating
      codon 61 mutation which resulted in the initial identification of N-ras from SK-N
      SH DNA. Therefore, we analyzed the sequences of earlier passages and sublines of
      the SK-N-SH cell line, but mutations at codon 59 or 61 were not detected,
      suggesting that neither mutation was present in the primary tumor. Our results
      indicate that N-ras mutations may occur spontaneously during in vitro passage of
      cell lines but rarely, if ever, occur in primary neuroblastomas,
      pheochromocytomas, and MTCs. In addition, we have not found H-ras or K-ras
      mutations in any neuroblastoma cell line or primary pheochromocytoma.

PMID- 1998950
TI  - 8-Chloroadenosine 3',5'-monophosphate inhibits the growth of Chinese hamster
      ovary and Molt-4 cells through its adenosine metabolite.
AB  - 8-Chloroadenosine 3',5'-monophosphate has been reported to inhibit growth of
      various mammalian cell lines at micromolar concentrations. We have used Chinese
      hamster ovary cell lines with mutated cyclic AMP-dependent protein kinase or
      altered cyclic nucleotide metabolism to show that a metabolite, 8
      chloroadenosine, is formed in the medium and is the active inhibitor of cell
      growth in Chinese hamster ovary cells. Adding adenosine deaminase to the Chinese
      hamster ovary cell growth media removes the inhibition of cell growth attributed
      to 8-chloroadenosine 3',5'-monophosphate. Adenosine deaminase or dipyridamole
      also protects Molt-4 lymphoblasts from the growth-inhibitory effects of 8
      chloroadenosine 3',5'-monophosphate.

PMID- 1998951
TI  - Differential specificity of monochlorobimane for isozymes of human and rodent
      glutathione S-transferases.
AB  - Monochlorobimane (MCB) has been used as a glutathione (GSH) specific fluorescent
      probe capable of delineating GSH heterogeneity in cellular systems. Generally,
      low concentrations of MCB (less than 50 microM) have been used to quantitatively
      label GSH in rodent cell lines. Incubation of the hamster cell lines, CHO AB1 and
      V79, with 10 microM MCB labeled 75 and 39% of the reduced GSH pool, respectively.
      In contrast, incubation of 7 different human cell lines with 10 microM MCB
      labeled less than 4% of the total reduced GSH pool. The human cell lines required
      1000 microM MCB to label an average of 73% of the GSH pool (range, 60-88%). When
      using 1000 microM MCB to label GSH, flow cytometry results from 7 different cell
      lines (human and rodent) were in good agreement with high performance liquid
      chromatography and standard spectrophotometric analysis with regards to a rank
      ordering of the GSH content determined for each cell line. The human glutathione
      S-transferases B2B2, B1B2, psi, pi, and the rat transferases 1-2, 3-3, and 3-4
      were isolated and purified for steady state kinetic analysis with MCB and GSH as
      the primary substrates. The human basic transferases, B1B2 and B2B2, had Km
      values for MCB of 354 and 283 microM and Vmax values of 33.3 and 34.6 mumol
      bimane-GSH/min/mg protein, respectively. The rat basic transferase 1-2 showed
      similar kinetic results with a Km of 199 microM and a Vmax of 35.5 mumol bimane
      GSH/min/mg protein. The human neutral transferase (psi) had a Km for MCB of 204
      microM with a Vmax of 6.5 mumol bimane-GSH/min/mg protein. In contrast, MCB has a
      high affinity for the rat neutral transferase with a Km of 2.6 microM and a Vmax
      of 35.1 mumol bimane-GSH/min/mg protein. The human acidic transferase (pi), the
      predominate transferase found in most human tumor cell lines, has a Km of 264
      microM for MCB and a Vmax of 1.99 mumol bimane-GSH/min/mg protein. The kcat/Km
      values indicated that MCB is an excellent substrate for the rat neutral
      transferases while the human pi glutathione S-transferase showed the least
      reactivity. Collectively the data indicate that MCB fails to label GSH at lower
      concentrations (less than 50 microM) in human cell lines because of the reduced
      affinity of MCB for the human transferases and possibly also due to differences
      in glutathione S-transferase isozyme expression between rodent and human cell
      lines.

PMID- 1998952
TI  - Cell membrane signaling as target in cancer therapy: inhibitory effect of N,N
      dimethyl and N,N,N-trimethyl sphingosine derivatives on in vitro and in vivo
      growth of human tumor cells in nude mice.
AB  - Sphingosine (SPN) has been claimed to be a negative modulator of transmembrane
      signaling through protein kinase C (PK-C) or some yet unidentified mechanism [for
      review see Y. A. Hannun and R. M. Bell, Science (Washington DC), 243: 500-507,
      1989]. N,N-Dimethylsphingosine (DMS) was recently found to be a physiological
      cellular component and, in comparison to SPN, to show a stronger and
      stereospecific inhibitory effect on PK-C activity of A431 cells (for review see
      Y. Igarashi, Trends Glycosci. Glycotechnol., 2: 319-332, 1990; and S. Hakomori,
      J. Biol. Chem., 265: 18713-18716, 1990). (4E)-N,N,N-Trimethyl-D-erythro
      sphingenine (TMS) is not detectable as a normal cellular component; however, it
      is expected to exhibit potent activity because of its quaternary ammonium ion
      structure, and in fact it showed much stronger inhibitory effect than DMS or SPN
      on PK-C activity (which plays an important role in cell growth regulation) in
      vitro. In view of these findings, we investigated the effects of SPN, DMS, and
      TMS on in vitro growth of various human carcinoma cell lines and on in vivo tumor
      growth in athymic nu/nu mice. Both DMS and TMS showed similar in vitro and in
      vivo growth inhibitory effects on tumor cells, despite the fact that TMS showed a
      much stronger inhibitory effect than DMS on PK-C activity of A431 cells. In
      contrast, SPN showed only a weak effect on in vitro cell growth and no effect on
      in vivo tumor growth. Tumor growth following s.c. inoculation of mice with human
      gastric carcinoma cell line MKN74 was inhibited in a dose-dependent manner by
      DMS, and tumor size was decreased after three or four consecutive daily
      injections of 0.5-mg doses of DMS or TMS. Increased tumor growth occurred after
      administration of these compounds was stopped; however, size of tumor remained
      significantly smaller than in groups treated with SPN or control saline. The
      effect of DMS or TMS on in vitro or in vivo MKN74 cell growth was stronger than
      that of 8-chloro-adenosine-cyclic 3':5'-monophosphate dihydrate, the most
      promising agent currently being used in clinical trials for inhibition of tumor
      growth by induction of differentiation. These results suggest that DMS or TMS
      could be useful anticancer agents through modification of transmembrane signaling
      related to cancer cell growth.

PMID- 1998953
TI  - Galactose-conjugated antibodies in cancer therapy: properties and principles of
      action.
AB  - Galactose conjugation of antibodies causes them to be recognized by the hepatic
      asialoglycoprotein receptor and therefore cleared very rapidly from the blood. In
      these investigations, some effector functions of galactose-conjugated antibodies
      were assayed, and several applications to experimental tumors in vivo were
      demonstrated. Galactose conjugation did not interfere with two antibody functions
      in addition to antigen binding, namely complement-mediated cytotoxicity and
      antibody-dependent cell-mediated cytotoxicity. This conjugation procedure was
      originally developed for its potential use in localized immunotherapy, such as
      i.p. Injection of galactose-antibody conjugates i.p. demonstrated, more
      conclusively than other methods that have been used, that the presence of ascites
      causes prolonged retention of antibody in the peritoneal cavity and that this
      effect is correlated with the volume of ascites present. In mice bearing i.p.
      tumor xenografts, i.p. injection of galactose-antibody conjugates resulted in
      high tumor/nontumor ratios at 28 h after antibody injection, with values of 40:1,
      43:1, 77:1, and 11:1 for the blood, kidney, lung, and spleen, respectively,
      although the ratio was only 4:1 for the liver. Control experiments demonstrated
      that i.p. injection of unconjugated antibody or a galactose-conjugated
      nonreactive antibody produced much lower tumor/nontumor ratios. In investigations
      of possible systemic application of galactose-antibody conjugates, we found that
      injection of large amounts of an inhibitor that binds competitively to the
      hepatic receptor, asialo-bovine submaxillary mucin, can block clearance of
      galactose-conjugated antibodies for 2-3 days. In this way, high blood levels of
      antibody can be maintained for 2-3 days, thus allowing penetration and binding to
      solid tumors, followed by very rapid blood clearance. With this approach, using a
      human carcinoma growing s.c. in nude mice, high tumor/nontumor ratios were
      obtained 4 days after injection, with mean values of 43:1, 18:1, 17:1, and 15:1
      for the blood, kidney, lung, and spleen, respectively, although the ratio for the
      liver was only 1.7:1. The blood level at this time was 0.04 +/- 0.02% (SD) of the
      injected dose/g, while the tumor level was 1.69 +/- 1.29% of the injected dose/g.
      In conclusion, galactose-conjugated antibodies appear to have diverse
      applications in regional or systemic immunotherapy.

PMID- 1998954
TI  - Activated ras alleles in human carcinoma of the prostate are rare.
AB  - Although oncogenically activated ras alleles are common in some types of human
      cancers, the frequency in human carcinoma of the prostate (CaP) has not
      previously been addressed. In this paper, we report a comprehensive screening of
      19 CaPs and 3 CaP cell lines for activating point mutations in the sequences of
      the 12th and 61st codons of c-Ha-ras-1 and the c-Ki-ras-2 genes, as well as the
      12th, 13th, and 61st codons of the c-N-ras gene. The 19 CaPs were chosen to
      represent a wide range of stages (B through D), Gleason scores (3 through 10),
      and DNA ploidy (diploid with low proliferation to nontetraploid-aneuploid).
      Fifteen of the tumors had been untreated prior to resection and 4 were obtained
      postradiation therapy. The polymerase chain reaction was used to amplify genomic
      DNA sequences and transcribed mRNA sequences of the ras genes prior to allele
      specific oligonucleotide probe hybridization. We have detected a mutant allele
      with a point mutation in the second nucleotide of the 61st codon of the c-Ha-ras
      1 gene in one specimen. Thus, we conclude that the activation of ras alleles is
      not significant in the development or progression of most CaPs.

PMID- 1998955
TI  - The multidrug resistance phenotype: 31P nuclear magnetic resonance
      characterization and 2-deoxyglucose toxicity.
AB  - In order to identify changes in 31P nuclear magnetic resonance (NMR) spectra
      associated with multiple drug resistance (MDR), a number of wild type and drug
      resistant cancer cell lines were studied. The resistant cells included cells
      selected with various drugs, mainly Adriamycin, as well as cells transfected with
      the human multidrug resistance gene (MDR1 gene), which encodes P-glycoprotein. In
      most cases, 31P NMR spectra were significantly different from those of parental,
      drug-sensitive lines. The spectra of resistant cells generally indicated
      increased levels of ATP and phosphocreatine in the cytoplasm. These changes are
      compatible with the increased glucose utilization rate previously described for
      resistant cells. Major changes were also observed in the levels of
      glycerophosphocholine and glycerophosphoethanolamine. Changes in cellular
      metabolism reflected by 31P NMR spectra depend on the drug used to select the
      cells for MDR. The direction of these changes was not consistent for all cell
      lines studied and could not be directly attributed to expression of P
      glycoprotein, suggesting that the changes may be related to alterations in
      metabolism and membrane function associated with other mechanisms of MDR. The
      results demonstrate the suitability of 31P NMR for studies of biochemical changes
      associated with MDR. The toxicity of 2-deoxyglucose, a glucose antimetabolite,
      was investigated in addition to the NMR studies and was found to be consistently
      higher in multidrug-resistant cells than in the parental drug-sensitive lines.
      For MCF-7 breast cancer cells, where several sublines with different levels of
      resistance were available, the toxicity was highest for the most resistant lines.

PMID- 1998956
TI  - Biological and clinical effects of intravenous tumor necrosis factor-alpha
      administered three times weekly.
AB  - Tumor necrosis factor (TNF) is a cytokine with pleiotropic biological and
      antitumor effects in vitro and in mouse models. The immunological effects of the
      molecule as a single agent, however, have not been well studied clinically. We
      conducted a Phase I trial of TNF in 53 patients with advanced malignancies in
      order to determine the biological and clinical effects of TNF when administered
      as a 30-min i.v. infusion three times/week. Dose levels of TNF ranged from 5 to
      275 micrograms/m2; doses of TNF were escalated between patient groups. The most
      common clinical toxicities of TNF consisted of rigors, anorexia, headache, and
      fatigue. Dose-limiting toxicity consisted of hypotension, fatigue, and nausea.
      Four patients treated at the maximally tolerated dose of 225 micrograms/m2
      received dexamethasone to determine whether the toxicities of TNF could be
      ameliorated. No significant differences in hypotension or subjective
      symptomatology were observed in those patients receiving dexamethasone and those
      who did not or between injections in which dexamethasone was administered and
      when it was not. One patient with colorectal carcinoma treated with 50
      micrograms/m2 had a partial response lasting about 9 months. Biological responses
      were evaluated in 8 patients treated at the maximally tolerated dose before
      therapy and 24 h afterward. TNF significantly (P less than 0.05 for all) enhanced
      serum beta 2-microglobulin, serum neopterin, and serum interleukin-2 receptor
      (Tac antigen) levels. Indoleamine 2,3-dioxygenase activity was also increased 24
      h following the administration of TNF, although this increase was only of
      borderline statistical significance (P = 0.07). TNF did not enhance granulocyte
      bactericidal activity. The expression of cell surface proteins on monocytes,
      including HLA-DR, HLA-DQ, beta 2-microglobulin, and the Fc receptor, and serum
      interleukin-1 activity also were not significantly increased by the
      administration of TNF. Thus, in humans TNF caused biological response modulation
      with evidence of HLA Class I (beta 2-microglobulin) increase and T-cell (Tac
      antigen) and monocyte (neopterin) activation.

PMID- 1998957
TI  - Temporal mapping of the differentiation pathway of the murine erythroleukemia
      cell.
AB  - These studies are concerned with "mapping" the temporal order of the
      precommitment events in the differentiation pathway of the Friend erythroleukemia
      cell. We have used a single-block procedure in which a differentiation-specific
      inhibitor of a temperature-sensitive (ts) differentiation-defective mutation was
      used to block the differentiation program. Later, the block was removed,
      differentiation was allowed to proceed, and the time required to reach a
      reference marker was monitored. These studies have indicated that the mutations
      tsC2GP1 and tsB5A, the poly(ADP-ribose) polymerase inhibitor 3-aminobenzamide,
      and the glucocorticoid hormone dexamethasone blocked functions which are required
      just prior to commitment. We have also used a double-block procedure involving
      two consecutive restrictive conditions, which suggests that the 3-aminobenzamide-
      and tsC2GP1-blocked functions constitute a part of a sequentially ordered pathway
      leading to terminal differentiation. The convergence of the 3-aminobenzamide,
      dexamethasone, and ts mutational blocks just prior to commitment suggests that
      the blocked functions may be part of a major control mechanism for commitment. In
      these studies, we have introduced a cytochalasin B-based assay to monitor
      commitment. The use of cytochalasin B permits a direct assay for commitment and
      obviates the need for colony-forming assays using semisolid medium, which have
      inherent problems such as efficiency of plating.

PMID- 1998958
TI  - Chromosome 9 deletion mapping reveals interferon alpha and interferon beta-1 gene
      deletions in human glial tumors.
AB  - We have applied restriction fragment length polymorphism analysis to a 30-member
      panel of primary glioma DNAs, which had been previously examined for loss of
      genetic information (C. D. James, E. Carlbom, J. P. Dumanski, M. Hansen, M.
      Nordenskjold, V. P. Collins, and W. K. Cavenee, Cancer Res., 48:5546-5551, 1988),
      to determine the frequency and sublocalization of loss of genetic information
      from chromosome 9. We have also utilized scanning densitometry for dosage
      determination of the 9p-localized interferon alpha and interferon beta-1 genes
      among these same tumors. Our results reveal the following: (a) for those cases in
      which loss has occurred, the region of common loss lies on the short (p) arm of
      the chromosome; (b) loss of genetic information from the short arm of chromosome
      9 occurs frequently in glial tumors of intermediate (anaplastic, grade III) and
      high (glioblastoma, grade IV) histological malignancy (10 of 20 cases) but not in
      tumors of low (grade II) histological malignancy (0 of 10 cases); (c) tumors with
      9p deletions are hemi- or nullizygous for interferon beta-1 and the interferon
      alpha gene cluster; (d) cases of interferon nullizygosity occur exclusively among
      tumors of highest histological malignancy (glioblastoma). These data, especially
      the determination of a region of nullizygosity, suggest proximity to or residence
      within a gene(s) whose function(s) is (are) critical to the suppression of the
      malignant evolution of glial tumors.

PMID- 1998959
TI  - Assessment of ligand effects in intracellular trafficking of ricin A chain using
      anti-ricin hybridomas.
AB  - Intracellular ricin and immunotoxin trafficking has been difficult to study as
      only one to two cytosolic ricin A chain (RTA) molecules are sufficient to cause
      cell death. Previous studies (R.J. Youle and M. Colombatti, J. Biol. Chem., 262:
      4676-4882, 1987) using anti-ricin hybridomas identified the secretory pre-Golgi
      as a critical site for RTA intoxication. We used ricin and RTA immunotoxins
      constructed with transferrin (TF) or anti-murine TF receptor antibody (RI7/217)
      to compare patterns of cytotoxicity and intracellular trafficking in anti-ricin
      hybridomas. Anti-RTA and anti-ricin B chain (RTB) hybridomas bound similar
      amounts of ricin and secreted comparable amounts of anti-ricin immunoglobulin.
      Anti-RTA hybridomas were 50- to 500-fold more resistant to ricin than
      nonsecretory and anti-RTB hybridomas, defining a ricin-resistant phenotype. All
      hybridomas expressed similar levels of surface TF receptors. RTA immunotoxins
      were constructed using human TF or RI7/217 and a disulfide linker. In protein
      synthesis inhibition assays, ricin-resistant hybridomas were manyfold more
      resistant to RI7/217-RTA than were ricin-sensitive hybridomas. In contrast, all
      hybridomas were equally sensitive to TF-RTA. Monensin increased ricin
      cytotoxicity minimally against all hybridomas, but dramatically increased RI7/217
      RTA cytotoxicity in ricin-resistant and ricin-sensitive hybridomas in a way that
      abrogated the ricin-resistant phenotype. In contrast, monensin increased TF-RTA
      cytotoxicity equally in all hybridomas. Ammonium chloride had little effect on
      ricin or RI7/217-RTA cytotoxicity, but increased TF-RTA cytotoxicity against all
      hybridomas. Taken together, these results suggest that RTA molecules mediating
      cytotoxicity pass through an anti-RTA antibody-containing pre-Golgi compartment
      when bound to RTB or RI7/217, but not when bound to TF. Monensin abrogates the
      ricin-resistant phenotype when RTA is linked to RI7/217, but not RTB. This
      suggests that monensin alters RI7/217-RTA processing proximal to the pre-Golgi
      and that passage through the pre-Golgi may not be necessary for translocation of
      RTA to the cytoplasm. Ammonium chloride alters toxin cytotoxicity only when RTA
      is linked to TF, suggesting that only TF trafficks RTA through an acid-sensitive
      compartment prior to cytoplasmic translocation. With the addition of potentiating
      agents, each toxin studied showed a unique cytotoxicity profile against the anti
      ricin hybridomas, demonstrating a dominant role of the cell binding ligand in
      intracellular toxin trafficking.

PMID- 1998960
TI  - Pharmacological evaluation of experimental isolated liver perfusion and hepatic
      artery infusion with 5-fluorouracil.
AB  - The intention of this study was to estimate the pharmacological advantage of a
      clinically applicable method of isolated liver perfusion (ILP) over hepatic
      artery infusion (HAI) administering various doses of 5-fluorouracil (FUra). FUra
      concentrations were measured using high-performance liquid chromatography in
      liver tissue (pigs and rats), hepatic tumor tissue (rats), and in the systemic
      circulation (pigs) following ILP and HAI. Forty-two pigs and 36 rats were
      subjected to either ILP or HAI with 20, 40 or 80 mg of FUra/kg of body weight.
      ILP resulted in significantly increased FUra concentrations in the liver as
      compared with the results with HAI in rats and pigs. Median areas under the
      concentration-time curve in liver tissue were 122.7 mumol.g-1.min and 59.9
      mumol.g-1.min (40-mg/kg dose-group) and 236.3 mumol.g-1.min and 45.1 mumol.g
      1.min (80 mg/kg) for ILP and HAI, respectively in pigs (both P less than 0.05).
      Systemic plasma areas under the curve were significantly lower for ILP as
      compared with HAI in 40- and 80-mg/kg dose-groups with 2.2 mumol.ml-1.min and 9.2
      mumol.ml-1.min (40 mg/kg; P less than 0.01) and 6.8 mumol.ml-1.min and 43.2
      mumol.ml-1.min (80 mg/kg; P less than 0.01) for ILP- and HAI-treated pigs,
      respectively. In hepatic tumor tissue a dose-dependent increase of mean FUra
      concentration was found for ILP-treated rats (P less than 0.05). No significant
      differences were observed in median FUra concentrations in tumor tissue between
      ILP- and HAI-treated rats (0.66 mumol.g-1 and 0.63 mumol.g-1 for ILP- and HAI
      treated groups with 80 mg/kg; P greater than 0.05). The mean FUra concentration
      tumor/liver ratio was 0.26. In order to clarify the metabolic fate of high-dose
      FUra, five rats were subjected to HAI with 150 mg of FUra/kg, and hepatic tumor
      extracts excised at t = 0 min, t = 5 min, and t = 15 min after infusion were
      analyzed using 19F nuclear magnetic resonance. Catabolite alpha-fluoro-beta
      alanine appeared rapidly at t = 5 min and t = 15 min in liver tissue. Significant
      amounts of the presumed active nucleotides were not detected in tumor tissue. We
      conclude that ILP is a means to improve selectivity of administration of
      antitumor agents to the liver, as compared with HAI. The pharmacological
      advantage of ILP over HAI administering equivalent doses of FUra was not
      demonstrated in tumor tissue, because of a large differential between liver
      tissue extraction and tumor tissue extraction of FUra, which was influenced by
      the mode of administration.

PMID- 1998961
TI  - Had-1, a uridine 5'-diphosphogalactose transport-defective mutant of mouse
      mammary tumor cell FM3A: composition of glycolipids, cell growth inhibition by
      lactosylceramide, and loss of tumorigenicity.
AB  - Glycolipid compositions of mouse mammary tumor cell FM3A and its Newcastle
      disease virus-resistant mutant cell, Had-1, which was also characterized as a
      defective mutant of UDP-galactose transport to Golgi apparatus, have been
      studied. The major neutral glycolipid in FM3A was Gal beta 1-4Glc beta 1-1Cer
      (LacCer) (95%) and the rest was Glc beta 1-1Cer. The concentration of neutral
      glycolipids in Had-1 was only about one-fifth of that in FM3A. GlcB1-1Cer in Had
      1 accounted for 79% of neutral glycolipids and the rest was LacCer, the content
      of which was decreased to 4% of that in FM3A. Ganglioside patterns of the two
      cell lines were similar, although gangliosides with N-glycolylneuraminic acid
      were increased in Had-1 cells compared with that in FM3A cells. The presence of
      NeuAc alpha 2-3-Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc beta 1-1Cer, NeuAc
      alpha 2-3Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc
      beta 1-2Cer, GM3, and GD3 was demonstrated by thin-layer chromatography
      immunostaining. 125I-Labeled Newcastle disease virus bound only poorly to
      gangliosides extracted from either FM3A or Had-1 cells on a high performance thin
      layer chromatography plate. The effects of glycolipids on the growth of the two
      cell lines were also studied. Had-1 cells were more sensitive to glycolipids
      added exogenously than FM3A cells. Addition of GM3 had a stimulative effect on
      cell growth of Had-1. LacCer, Gal beta 1-3GalNAc beta 1-4Gal beta 1-4Glc beta 4
      1Cer, and Glc beta 1-1Cer inhibited the growth of Had-1 cells. LacCer was the
      most potent inhibitor. LacCer immobilized on the culture plate also inhibited the
      growth of Had-1 cells. The inhibitory effect was recovered completely overcome by
      transferring the cells to LacCer-free medium. Had-1 cells were not tumorigenic in
      C3H/He mice, and furthermore the tumorigenic activity of FM3A cells was
      suppressed by the prior administration of Had-1 cells.

PMID- 1998962
TI  - Effect of alkyl-lysophospholipid on glioblastoma cell invasion into fetal rat
      brain tissue in vitro.
AB  - The antitumor effect of alkyl-lysophospholipid (ALP) was studied on a continuous
      glioma cell line (GaMg) as well as on tumor spheroids obtained from three
      different primary brain tumor biopsies. GaMg monolayer growth was reduced by 50%
      after treatment with 30 microM ALP; cells accumulated in the G2M phase of the
      cell cycle as determined by flow-cytometric analyses. Tumor spheroid growth was
      reduced by 25 and 44% during treatment with 10 and 30 microM ALP, respectively.
      These drug concentrations also caused a severe destruction of spheroids. No
      effect on growth or morphology was seen in spheroids treated with 0.1 and 1.0
      microM ALP. ALP caused a dose-dependent inhibition of invasion by GaMg tumor
      spheroids into brain aggregates. After 168 h of 1.0 microM ALP treatment, the
      volume of the intact brain aggregate was 90% larger than that in the untreated co
      cultures. To further investigate the efficacy of ALP as an anti-invasive drug, co
      cultures were performed with specimens obtained from three primary brain tumors:
      a highly invasive glioblastoma multiforme, an anaplastic astrocytoma, and an
      astrocytoma. Treatment of spheroids from the most invasive tumor with ALP caused
      a 7-fold preservation of normal brain tissue relative to control co-cultures.
      Moreover, the sensitivity of primary glioma spheroids to the anti-invasive effect
      of ALP seemed to be associated with the aggressiveness of the tumor; spheroids
      from the more malignant specimen (glioblastoma multiforme) were more sensitive
      than those from the less aggressive tumors. The anti-invasive effect seen with
      nontoxic concentrations of ALP may prove valuable in the treatment of malignant
      gliomas.

PMID- 1998963
TI  - Inducible expression of calcyclin, a gene with strong homology to S-100 protein,
      during neuroblastoma cell differentiation and its prevalent expression in Schwann
      like cell lines.
AB  - Calcyclin gene expression was evaluated in different neuroblastoma cell lines and
      during neuronal differentiation induced by retinoic acid. Calcyclin gene
      expression was more frequently detected in epithelial-type or Schwann-like cells
      rather than in neuroblastic cells. This result indicates an increase of G1 cell
      fraction, which may explain the limited growth potential usually observed for
      these cells. LAN-5 cell (neuronal type) differentiation experiments showed that
      calcyclin gene is detectable after 4 days of retinoic acid treatment, which
      induces G1 phase accumulation (as detected by cytofluorometric analysis), and
      cell growth arrest. Otherwise, neither block of cell proliferation by 0.5% fetal
      calf serum medium nor addition of 15% fresh fetal calf serum after cell arrest
      induce calcyclin expression. The increase of calcyclin mRNA levels during cell
      differentiation shows that calcyclin gene expression is associated with neuronal
      differentiation. This bivalent role of the calcyclin gene, which is normally
      expressed in the G1 phase of the cell cycle but also expressed during retinoic
      acid-induced neuroblastoma cell differentiation, suggests that (at least in
      neuroblastoma cells) the gene is subject to a complex transcriptional regulation.

PMID- 1998964
TI  - Interleukin 3-dependent proliferation of the human Mo-7e cell line is supported
      by discrete activation of late G1 genes.
AB  - The hemopoietic growth factor interleukin 3 (IL-3) supports the survival and
      proliferation of multipotent and committed progenitor cells in vitro. To
      elucidate the molecular mechanisms triggered by IL-3 we studied the expression of
      cell cycle-related genes in a recently established human IL-3-dependent clone (M
      07e). No changes in the level of expression of early (c-myc), mid (ornithine
      decarboxylase), or mid-late G1 (p53, c-myb) cell cycle genes were detected after
      restoration of IL-3 in deprived cells. The fact that only late G1-S-phase genes
      [proliferating cell nuclear antigen (PCNA) thymidine kinase (TK), histone H3] are
      modulated by IL-3 suggests that this factor may control human cell proliferation
      by acting at the G1-S boundary.

PMID- 1998965
TI  - Specific inhibition of K-ras expression and tumorigenicity of lung cancer cells
      by antisense RNA.
AB  - A human lung cancer cell line (H460a) with a homozygous spontaneous K-ras
      mutation was transfected with a recombinant plasmid that synthesizes a 2-kilobase
      genomic segment of the K-ras protooncogene in antisense orientation. Translation
      of the mutated K-ras mRNA in H460a cells was specifically inhibited, whereas
      expression of H-ras and N-ras was unchanged. A 3-fold growth inhibition occurred
      in H460a cells when expression of the mutated ras p21 protein was down-regulated
      by antisense RNA. However, cells remained viable despite the absence of K-ras
      expression. The growth of H460a tumors in nu/nu mice was substantially reduced by
      expressed K-ras antisense RNA.

PMID- 1998966
TI  - Correspondence re: Xiu F. Hu et al., Combined use of cyclosporin A and verapamil
      in modulating multidrug resistance in human leukemia cell lines. Cancer Res., 50:
      2953-2957, 1990.

PMID- 1998967
TI  - Professionalism and the Christian nurse.

PMID- 1998968
TI  - Teaching nurses in Hong Kong.

PMID- 1998969
TI  - A murine plasmacytoma MOPC 104E resistant to cyclophosphamide is resistant to
      immunotherapy.
AB  - A murine plasmacytoma MOPC 104E (MOPC) is highly sensitive to chemotherapeutic
      agents such as cyclophosphamide and mitomycin C as well as to immunotherapy (OK
      432-combined adoptive immunotherapy using interleukin-2-cultured killer cells).
      In the present study, we prepared cyclophosphamide-resistant MOPC cells (MOPC
      CPA/R) by serial in vivo passage of tumor cells following cyclophosphamide
      treatment. The in vivo sensitivity of MOPC-CPA/R to mitomycin C or to
      immunotherapy (OK-432-combined adoptive immunotherapy) was significantly
      decreased compared to the parent MOPC. In vitro experiments showed that MOPC
      CPA/R were more resistant (five-fold) to lysis by cultured immune spleen cells
      than MOPC. Inhibition of the lytic activity of cultured immune spleen cells
      against MOPC was significantly increased (P less than 0.05) by the addition of
      unlabeled MOPC compared to unlabeled MOPC-CPA/R. These results suggest that MOPC
      CPA/R express weaker antigenicity than MOPC. However, the transfer of immune
      spleen cells cultured with tumor extract derived from MOPC-CPA/R significantly
      prolonged the survival of MOPC-CPA/R-inoculated mice. Thus, by repeated
      cyclophosphamide treatment, tumor cells with low-antigenicity were selected.
      These tumor cells had lower sensitivity to another chemotherapeutic agent and
      immunotherapy. Such an immunological response may play an important role in
      cancer therapy.

PMID- 1998970
TI  - Blocked and non-blocked ricin immunotoxins against the CD4 antigen exhibit higher
      cytotoxic potency than a ricin A chain immunotoxin potentiated with ricin B chain
      or with a ricin B chain immunotoxin.
AB  - An immunotoxin consisting of ricin A chain linked to the monoclonal antibody M
      T151, recognising the CD4 antigen, was weakly toxic to the human T-lymphoblastoid
      cell line CEM in tissue culture. The incorporation of [3H]leucine by CEM cells
      was inhibited by 50% at an M-T151--ricin-A-chain concentration (IC50) of 4.6 nM
      compared with an IC50 of 1.0 pM for ricin. In contrast, immunotoxins made by
      linking intact ricin to M-T151 in such a way that the galactose-binding sites of
      the B chain subunit were either blocked sterically by the antibody component or
      were left unblocked, were both powerfully cytotoxic with IC50 values of 20-30 pM.
      The addition of ricin B chain to CEM cells treated with M-T151--ricin-A-chain
      enhanced cytotoxicity by only eight-fold indicating that isolated B chain
      potentiated the action of the A chain less effectively than it did as an integral
      component of an intact ricin immunotoxin. Ricin B chain linked to goat anti
      (mouse immunoglobulin) also potentiated weakly. Lactose completely inhibited the
      ability of isolated ricin B chain to potentiate the cytotoxicity of M-T151--ricin
      A-chain and partially (3- to 4-fold) inhibited the cytotoxicity of the blocked
      and non-blocked ricin immunotoxins. Thus, in this system, the galactose-binding
      sites of the B chain contributed to cell killing regardless of whether isolated B
      chain was associated with the A chain immunotoxin or was present in blocked or
      non-blocked form as part of an intact ricin immunotoxin. The findings suggest
      that the blocked ricin immunotoxin may become unblocked after binding to the
      target antigen to re-expose the cryptic galactose-binding sites. However, the
      unblocking cannot be complete because the maximal inhibition of [3H]leucine
      incorporation by the blocked immunotoxin was only 80% compared with greater than
      99% inhibition by the non-blocked immunotoxin.

PMID- 1998971
TI  - Generation of lymphokine-activated killer cells in human ovarian carcinoma
      ascitic fluid: identification of transforming growth factor-beta as a suppressive
      factor.
AB  - The effect of cell-free ascitic fluid from patients with epithelial ovarian
      carcinoma on the generation of lymphokine-activated killer cells (LAK) was
      compared to the activity generated in control medium containing 10% fetal bovine
      serum, using Daudi target cells. Samples of ascitic fluid from nine different
      patients tested inhibited LAK generation. Suppressive activity was evident as
      early as 24 h of incubation in the presence of ascitic fluid and increasing
      suppression developed with prolonged exposure. Suppression was concentration
      dependent, present at 10%-20% and increasing with concentrations up to 80%. The
      suppressive effect of ascitic fluid was only partially reversed on increasing the
      concentration of interleukin-2 (IL-2) from 10 units to 1000 units/ml. Activated
      LAK appeared to maintain the majority of their activity on further culture in
      ascitic fluid in the presence of IL-2 but further enhancement of lytic activity
      was prevented. Fractionation of a suppressive sample by HPLC, using 0.1 M
      KCl/acetic acid buffer pH 2.6, revealed that the dominant peak of suppressive
      activity eluted at 25 kDa; with pH 7.0 TRIS-buffered saline, most of the activity
      was lost on the column. Antibody neutralization studies of the 25-kDa suppressive
      peak as well as on whole ascitic fluid have revealed that transforming growth
      factor beta (TGF beta) is the major suppressive factor present in ascitic fluid.
      Factors that suppress LAK generation in vitro were present in all samples tested.
      The effect on the lytic activity of activated LAK cells was minimal. This
      suggests that, in the clinical setting, the greatest impact would be achieved by
      activating LAK cells ex vivo and subsequently transferring them to the peritoneal
      cavity in the presence of IL-2 rather than by attempting to generate them in situ
      by injecting IL-2 into the peritoneal cavity. However, reversal of TGF beta
      mediated suppression in situ may be necessary to allow local proliferation of LAK
      cells to achieve an effective killer-to-target ratio.

PMID- 1998972
TI  - Improved radioimmunotherapy of colorectal cancer xenografts using antibody
      mixtures against carcinoembryonic antigen and colon-specific antigen-p.
AB  - Radioimmunotherapy of GW-39 human colonic tumor xenografts grown in the hamster
      cheek pouch with 131I-labeled NP-4 anti-(carcinoembryonic antigen) (CEA) and 131I
      labeled Mu-9 anti-(color-specific antigen-p) (CSAp) murine monoclonal antibodies,
      administered in combination, was more effective than using either antibody alone
      for tumor masses less than 0.5 cm3 in size. The antibody mixture had no
      therapeutic advantage for larger tumors. Therapeutic efficacy was determined by
      measuring the change in tumor size over time, quantifying the absolute number of
      tumors responding to radioantibody therapy, and determining the percentage growth
      inhibition of each treatment at various times after radioantibody administration.
      Several mechanisms are discussed to explain the improved tumoricidal effect of
      the antibody mixture noted in this model system, such as (a) the possibility that
      an antibody mixture could target a greater number of tumor cells, (b) the
      potential for antibody mixtures to provide better tumor distribution and (c) the
      possibility that antibodies administered in combination can increase the
      magnitude of tumor uptake of individual radioantibodies, thereby resulting in a
      greater radiation dose delivered to the tumor.

PMID- 1998974
TI  - Inhibition of human renal cancer by monoclonal-anti-body-linked methotrexate in
      an ascites tumor model.
AB  - The monoclonal antibody DAL K29 against a cell-surface antigen associated with a
      human renal cell carcinoma was covalently linked to the antifolate methotrexate
      with full retention of antibody activity and partial retention of drug activity.
      Using an ascites tumor model, developed after intraperitoneal (i.p.) inoculation
      of 5 x 10(6) cells of the human kidney cancer line Caki-1 per pristane-primed
      nude mouse, we showed that the methotrexate-Dal-K29 conjugate was a more potent
      tumor inhibitor (P less than 0.0005) of human renal cell carcinoma (which is
      resistant to currently available modalities including chemotherapy) than the drug
      or mAb alone, the drug linked to an isotype-matched nontumor-specific IgG or a
      mixture of the drug and the mAb. Only the conjugate could produce tumor-free
      survival in a proportion of the mice during the period of observation (i.e. 150
      days after tumor inoculation).

PMID- 1998975
TI  - [Home care of hospitalized psychotic patients].

PMID- 1998973
TI  - Hypotension and disseminated intravascular coagulation following intralesional
      bacillus Calmette-Guerin therapy for locally metastatic melanoma.
AB  - Four patients developed serious hypotension and signs of disseminated
      intravascular coagulation shortly after a second round of Tice bacillus Calmette
      Guerin (BCG) injections into locally recurrent cutaneous melanoma satellite
      nodules. Each of these patients survived following intensive therapy with
      isoniazid, pyridoxine, steroids, pressors, antibiotics, and cardio-renal support
      including, in one case, three acute hemodialyses. Plasma specimens from two of
      the four patients caused gelation of lysate from the amebocytes of Limulus
      polyphemus, indicating the presence of endotoxin or an endotoxin-like substance.
      In vitro studies on the BCG preparations led us to conclude that this endotoxin
      activity in the plasma is not the result of direct injection of endotoxin with
      the BCG preparation, but rather from release of endotoxin from endogenous
      sources, such as the intestinal tract during a period of relative hypotension
      following an allergic reaction. Prior immunity appeared to be the consistent
      factor in the toxic reactions reported herein. Finally, we present
      recommendations for serial monitoring of these patients and discuss the use of an
      alternative agent for intralesional therapy.

PMID- 1998976
TI  - [Retention of body temperature in premature infants].

PMID- 1998977
TI  - [Tachyarrhythmia treated with electric countershock in children].

PMID- 1998978
TI  - [Nursing care of diabetic patients with severe skin infections. Analysis of 15
      cases].

PMID- 1998979
TI  - [Nursing care of CT X-ray in severe brain injuries].

PMID- 1998980
TI  - [Psychologic analysis and nursing care of aged patients treated by
      counterpulsation].

PMID- 1998981
TI  - [Nursing care of pregnancy complicated with rheumatic heart disease].

PMID- 1998982
TI  - Saturation of 2',2'-difluorodeoxycytidine 5'-triphosphate accumulation by
      mononuclear cells during a phase I trial of gemcitabine.
AB  - The plasma and cellular pharmacology of 2',2'-difluorodeoxycytidine (dFdC,
      Gemcitabine) was studied during a phase I trial. The steady-state concentration
      of dFdC in plasma was directly proportional to the dFdC dose, which ranged
      between 53 and 1,000 mg/m2 per 30 min. The cellular pharmacokinetics of an active
      metabolite, dFdC 5'-triphosphate (dFdCTP), were determined in mononuclear cells
      of 22 patients by anion-exchange high-pressure liquid chromatography. The rate of
      dFdCTP accumulation and the peak cellular concentration were highest at a dose
      rate of 350 mg/m2 per 30 min, during which steady-state dFdC levels of 15-20
      microM were achieved in plasma. A comparison of patients infused with 800 mg/m2
      over 60 min with those receiving the same dose over 30 min demonstrated that the
      dFdC steady-state concentrations were proportional to the dose rate, but that
      cellular dFdCTP accumulation rates were similar at each dose rate. At the lower
      dose rate, the AUC for dFdCTP accumulation was 4-fold that observed at the higher
      dose rate. Consistent with these observations, the accumulation of dFdCTP by
      mononuclear cells incubated in vitro was maximal at 10-15 microM dFdC. These
      studies suggest that the ability of mononuclear cells to use dFdC for
      triphosphate formation is saturable. In the design of future protocols, a dose
      rate should be considered that produces maximal nucleotide analogue formation,
      with increased intensity being achieved by prolonging the duration of infusion.

PMID- 1998983
TI  - Positive therapeutic interaction between thiopurines and alkylating drugs in
      human glioma xenografts.
AB  - We used human anaplastic glioma xenografts to evaluate the therapeutic efficacy
      of combinations of alkylating drugs, either 1,3-bis(2-chloroethyl)-1-nitrosourea
      (BCNU), 1-(2-chloroethyl)-3-(2,5-dioxo-3-piperidyl)-1-nitrosourea (PCNU), or
      procarbazine, and thiopurines, either 6-mercaptopurine (6MP) or 6-thioguanine
      (6TG). Using growth delay as the endpoint in subcutaneous (s.c.) tumors and
      increased life span as the endpoint in intracranial (i.c.) tumors, we found that
      combinations of chloroethylnitrosoureas (CENUs) and thiopurines were
      significantly more active than either type of agent alone. In contrast,
      combinations of procarbazine and thiopurines were not significantly more active
      than procarbazine alone. The therapeutic potentiation of the CENU was greater
      when the latter was given on the 4th day of the thiopurine treatment cycle than
      when it was given on the 1st day. Characterization of the interaction between
      CENUs and thiopurines also revealed a supraadditive therapeutic response at
      higher BCNU doses in combination with 6TG. Interaction between the nitrosoureas
      and the thiopurines probably occurs in the guanine base of tumor DNA and has
      important therapeutic implications.

PMID- 1998985
TI  - Chemical stability of ecomustine, a new antitumor agent in aqueous and biological
      media as assessed by high-performance liquid chromatography.
AB  - Ecomustine, or CY233 (NSC-609224), is a new water-soluble nitrosoureido sugar
      derived from acosamine. A high-performance liquid chromatographic assay (HPLC)
      developed to quantify the unchanged drug in aqueous solutions and biological
      specimens enabled us to study the chemical stability as a function of pH, light,
      and temperature. In buffered aqueous solutions, the kinetics of degradation of
      CY233 is a first-order process. The log k-pH profile demonstrated hydroxide ion
      catalyzed solvolysis. The drug is most stable at pH 4, more stable than some
      other nitrosoureas in 5% glucose (t1/2, 62-67 h) and in 0.9% isotonic saline
      (t1/2, 25-37 h) solutions. Based on these findings, blood samples should be
      collected in cold tubes (4 degrees C) containing citrate buffer (pH 4) and all
      manipulations should be protected from heat and light.

PMID- 1998984
TI  - Disposition and metabolism in mice of the potential antitumor and anti-human
      immunodeficiency virus-1 agent, 2-chloro-2',3'-dideoxyadenosine.
AB  - A high-performance liquid chromatographic (HPLC) procedure was developed to
      examine the preclinical pharmacology and pharmacokinetics of 2-chloro-2',3'
      dideoxyadenosine (ClddAd). The HPLC assay for ClddAd in human plasma was linear
      from 0.25 to 500 micrograms ClddAd/ml. Coefficients of variation for the
      measurement of ClddAd in human plasma were 9.7%, 4.1%, and 2.7% at 2.5, 25, and
      250 micrograms/ml, respectively. Binding of ClddAd to human and mouse plasma
      proteins was determined by filtration to be 26.9% and 34.4%, respectively. ClddAd
      concentrations decreased by less than 5% when ClddAd was stored for 126 h at 37
      degrees C in 0.9% NaCl or 0.1 M NaH2PO4 (pH 7.4) or when ClddAd was stored for 24
      h at 37 degrees C in citrate-buffered human blood or plasma. Estimates of the
      lethal dose for 50% (LD50) and 10% (LD10) of male CD2F1 mice that received a
      single i.v. dose of ClddAd were 27 and 24 mg/kg, respectively. Elimination of a
      24-mg/kg i.v. bolus dose of ClddAd from mouse plasma was biphasic, with half
      lives of 0.73 and 14.7 min. The apparent volume of distribution of ClddAd was 215
      ml/kg and the total body clearance was 20 ml min-1 kg-1. No ClddAd metabolites
      were detected in mouse plasma after in vivo exposure or in human whole blood or
      plasma after in vitro incubation. ClddAd was detected in the urine of mice within
      2 min after exposure, and the total urinary excretion of unchanged ClddAd for 24
      h after exposure to 24 mg/kg was 3.4% of the delivered dose. At least two
      possible ClddAd metabolites were detected in mouse urine; they did not co-elute
      with 2-chloro-2',3'-dideoxyinosine,2-chloradenine, or 2-chlorohypoxanthine.

PMID- 1998986
TI  - In vitro evaluation of platinum, titanium and ruthenium metal complexes in
      cisplatin-sensitive and -resistant rat ovarian tumors.
AB  - The antitumor activity of eight new metal complexes (three platinum, one
      titanium, four ruthenium derivatives) was investigated in a cisplatin (DDP)-
      sensitive (O-342) and a DDP-resistant (O-342/DDP) ovarian tumor line using the
      bilayer soft-agar assay. A continuous exposure set up at logarithmically spaced
      concentrations was used to test the drugs; to uncover possible pharmacokinetic
      features, a short-term exposure was additionally included for selected compounds.
      DDP served as the reference drug. The following compounds were investigated: 18
      crown-6-tetracarboxybis-diammineplatinum(II) (CTDP), cis
      aminotrismethylenephosphonato-diammine-platinum(II) (ADP), cis
      diamminecyclohexano-aminotrismethylenephosphonato-platin um(II) (DAP),
      diethoxybis(1-phenylbutane-1,3-dionato)titanium(IV) (DBT, budotitane), trans
      imidazolium-bisimidazoletetrachlororuthenate(III) (ICR), trans-indazolium
      tetrachlorobisindazoleruthenate(III) (IndCR), cis-triazolium-tetrachlorobis
      triazoleruthenate(III) (TCR) and trans-pyrazolium
      tetrachlorobispyrazoleruthenate(III) (PCR). Of the new metal complexes, CTDP was
      the most active compound in O-342, resulting in a percentage of control plating
      efficiency (+/- SE) of 1 +/- 1, 12 +/- 8 and 40 +/- 21 following continuous
      exposure to 10, 1 and 0.1 microM, respectively, and was thus comparable to DDP at
      equimolar concentrations. In the resistant line, 10 microM CTDP reduced colony
      growth to 18% +/- 8%, whereas an equimolar concentration of DDP effected a
      reduction to 26% +/- 9%. During short-term exposure. CTDP was inferior to DDP,
      which may be ascribed to the stability of the bis-dicarboxylate platinum ring
      system. The titanium compound DBT, in contrast, showed promising effects at its
      highest concentration (100 microM) during short-term exposure in both lines; at
      this concentration the activity in O-342/DDP was higher than that in O-342 (7% +/
      7% vs 34% +/- 17% of control plating efficiency at 100 microM). All ruthenium
      complexes showed higher activity in the resistant line O-342/DDP than in the
      sensitive counterpart. ICR was the most active compound. Following continuous
      exposure of O-342/DDP cells to 10 microM ICR, colony growth was reduced to 18% +/
      4% that of controls. Further studies should concentrate on CTDP and ICR for the
      following reasons; the activity of CTDP was equal to that of DDP at equimolar
      concentrations during continuous exposure; considering that the in vivo toxicity
      of DDP was 3-fold that of CTDP, an increase in the therapeutic index of CTDP
      would be expected. ICR showed the best effect of all ruthenium complexes; it was
      superior to DDP in the resistant line.

PMID- 1998987
TI  - Bioavailability and pharmacology of oral idarubicin.
AB  - A total of 9 patients entered in a phase I trial who received oral idarubicin
      daily for 3 days took part in pharmacokinetic studies, and bioavailability
      studies were performed on 13 additional patients receiving single doses of oral
      idarubicin alternating with i.v. treatment. The data were best fit by a two
      compartment model (distribution and elimination compartments for i.v. drug and
      absorption and single-phase elimination for oral drug). For different idarubicin
      doses in the phase I and bioavailability studies, the median values for the
      terminal half-life of idarubicin varied from 5.6 to 11.6 h. High concentrations
      of the active metabolite idarubicinol were formed. Idarubicinol was eliminated
      more slowly than was the parent compound, with median half-lives for different
      dose levels varying from 8 to 32.7 h. Although most pharmacokinetic parameters
      were similar in plasma and whole blood, peak concentrations and AUCs in whole
      blood were about 3-4 times those calculated in plasma for idarubicin and about
      1.5-2 times those determined in plasma for idarubicinol, indicating fairly
      extensive uptake into erythrocytes. Oral bioavailability was determined by
      comparing oral idarubicin to i.v. drug with respect to the combined idarubicin
      and idarubicinol plasma AUCs, and it varied from 12%-49% (median, 29%).
      Bioavailability was essentially the same (30%) when whole-blood values were used.
      Urinary excretion of the drug was less than 5% of the delivered dose by 96 h.
      Granulocytopenia correlated with plasma idarubicinol "estimated" clearance and
      steady-state volume of distribution, with whole-blood idarubicinol AUC, area
      under the moment curve (AuMC), and "estimated" clearance and volume of
      distribution, and with whole-blood combined idarubicin and idarubicinol AUCs.
      This suggests that drug contained in erythrocytes plays a major role in toxicity
      and that idarubicinol may play a larger role in toxicity than does the parent
      compound.

PMID- 1998988
TI  - Mechanism of action of psoralens: isobologram analysis reveals that ultraviolet
      light potentiation of psoralen action is not additive but synergistic.
AB  - The combination of psoralens and ultraviolet light (UVA, 320-400 nm), referred to
      as PUVA, inhibits proliferation of a variety of cell types. In the present
      studies, we used S-180 cells to investigate the mechanism underlying the
      antiproliferative actions of PUVA. We found that inhibition of growth of S-180
      cells by PUVA was dependent on the concentration of psoralen as well as the dose
      of UVA light. Neither the psoralens nor UVA light by themselves inhibited cell
      growth. Several clinically important psoralen analogs inhibited cell growth. The
      potent phototoxin 4,5',8-trimethylpsoralen was the most active psoralen analog
      tested, followed by 5-methoxypsoralen and 8-methoxypsoralen. The angular
      furocoumarin, 5-methylangelicin, was the least active inhibitor of growth.
      Multivariate (isobologram) analysis of the growth-inhibition curves revealed that
      combinations of psoralens and UVA light were not simply additive but synergistic.
      Similar results were observed when inhibition of DNA synthesis was used as an
      endpoint for the biological effects of PUVA. These studies are the first to
      demonstrate that psoralens and UVA light act synergistically. Our results suggest
      that the synergism between the psoralens and UVA light may be an important
      property of PUVA that contributes to its therapeutic efficacy in proliferative
      diseases.

PMID- 1998989
TI  - Measurement of in vitro cellular pharmacokinetics of 5-fluorouracil in human and
      rat cancer cell lines and rat hepatocytes using a flow-through system.
AB  - A flow-through system was used to study the cellular pharmacokinetics of 5
      fluorouracil (5-FU) in four human cell lines (squamous-cell carcinoma HEp-2,
      colon carcinoma WiDr, hepatoma Hep G2, and breast carcinoma MCF-7) as well as in
      the rat hepatoma H35 cell line and in freshly isolated rat hepatocytes. The
      system made it possible to restrict the decrease in the concentration of 5-FU in
      the medium, to keep the volume in which the metabolites accumulated relatively
      small, and to study the dynamics of a response during and after a change in the
      composition of the eluent. Clearance of 5-FU from the eluent was achieved
      predominantly (greater than 95%) by its catabolism to dihydrofluorouracil in the
      tumor cell lines and to 2-fluoro-beta-alanine in the hepatocytes. Not only rat
      hepatocytes but also HEp-2 cells showed relatively high clearance values. A
      concentration-dependent 5-FU elimination was observed, indicating saturation of 5
      FU elimination according to Michaelis-Menten kinetics (Km 14-22 microM). The
      maximal velocity (Vmax) values ranged from 0.025 to 0.13 nmol 5-FU/10(6) cells
      per minute. For HEp-2 cells, high-concentration pulse injections of 5-FU,
      thymine, uridine, or uracil immediately led to a reduction in 5-FU conversion,
      followed by recovery within 5 min. The flow-through system proved to be adequate
      for the study of the non-linear pharmacokinetics of 5-FU in different intact
      cells and for the comparison of various manipulations of these pharmacokinetics.

PMID- 1998990
TI  - A clinical study of nafazatrom in advanced human breast cancer.
AB  - Prostaglandins (PGs) have been shown to inhibit tumour metastases in experimental
      animal systems. Nafazatrom is a pyrazolinone derivative that increases endogenous
      prostacyclin (PGI2) and has experimental anti-cancer activity. In the present
      study, nafazatrom was given to 47 women with advanced breast cancer; objective
      remission of metastases was seen in 2 patients and stabilisation of disease in 1
      case. Nafazatrom was safe and well tolerated.

PMID- 1998991
TI  - Acute reversible neurological deficit following intrathecal chemotherapy.
AB  - We report on two patients with non-Hodgkin's lymphoma (NHL) who developed
      reversible, short-lived neurological deficit following intrathecal (i.t.)
      chemotherapy. One patient received i.t. methotrexate for treatment of meningeal
      disease, and the other received i.t. methotrexate with cytosine arabinoside (ara
      C) and hydrocortisone as central nervous system (CNS) prophylaxis. Although
      transient paresis following i.t. chemotherapy has previously been reported, it
      has been attributed to the preservatives contained in the diluents. Our two
      patients, however, received preservative-free solutions.

PMID- 1998992
TI  - Comparisons of tetrachloro(d,l-trans)1,2-diaminocyclohexane-platinum(IV)
      biotransformations in the plasma of Fischer 344 rats at therapeutic and toxic
      doses.
AB  - Plasma biotransformations of tetrachloro(d,l-trans)1,2
      diaminocyclohexaneplatinum(IV) (tetraplatin) were determined in vivo at both
      therapeutic (3 mg/kg) and toxic (12 mg/kg) doses in Fischer 344 rats. Tetraplatin
      was rapidly converted to dichloro(d,l-trans)1,2-diaminocyclohexaneplatinum(II)
      [PtCl2(dach)]. This conversion was complete at the earliest time measured (7.5
      min) at the therapeutic dose, but some unreacted tetraplatin was detectable in
      the circulation at the toxic dose. Three other major biotransformation products
      were observed in plasma: (d,l-trans)1,2-diaminocyclohexaneaquachloroplatinum(II)
      [Pt(H2O)(Cl)(dach)]+, the Pt-methionine complex, and another biotransformation
      product tentatively identified as either the Pt-cysteine or Pt-ornithine complex.
      Several other minor plasma biotransformation products were detected. Two of these
      were most likely formed intracellulary from tetraplatin. Two or more other
      platinum complexes appeared to lack the diaminocyclohexane carrier ligand and
      were most likely formed intracellulary by trans-labilization of the carrier
      ligand. Tetraplatin, PtCl2(dach), and [Pt(H2O)(Cl)(dach)]+ all rapidly
      disappeared from the circulation. The other biotransformation products were
      persistent through at least 3 h and could be responsible for the delayed toxicity
      of tetraplatin. Although some minor differences were observed between tetraplatin
      biotransformations at the toxic vs therapeutic doses, most biotransformation
      products were simply present at much greater concentrations at the toxic dose
      than at the therapeutic dose. Thus, our data suggest that dose-dependent
      differences in tetraplatin toxicity are probably attributable to the amount,
      rather than the type, of biotransformation products present in the plasma.

PMID- 1998993
TI  - Comparison of the cytotoxicity in vitro of temozolomide and dacarbazine, prodrugs
      of 3-methyl-(triazen-1-yl)imidazole-4-carboxamide.
AB  - The present study tested the hypothesis that the experimental antineoplastic
      imidazotetrazinone temozolomide degrades in the biophase to 3-methyl-(triazen-1
      yl)imidazole-4-carboxamide (MTIC) and exerts its cytotoxicity via this species.
      MTIC is a metabolite of the antimelanoma agent dacarbazine and is thought to be
      responsible for the antineoplastic activity of the latter. Cytotoxicity in vitro
      was investigated in TLX5 murine lymphoma cells. MTIC and temozolomide were
      cytotoxic in the absence of mouse-liver microsomes, whereas dacarbazine required
      metabolic activation. The generation of MTIC from either dacarbazine, its primary
      metabolite 5-[3-(hydroxymethyl)-3-methyl-triazen-1-yl]-imidazole-4-carboxamid e
      (HMMTIC) or temozolomide was studied by reversed-phase high-performance liquid
      chromatography in incubation mixtures under the conditions of the cytotoxicity
      assay. MTIC was found in incubations of temozolomide with or without microsomes.
      Dacarbazine yielded MTIC (and HMMTIC) only when microsomes were included in the
      incubation mixture. Although the mode of action of temozolomide seems to be
      similar to that of dacarbazine, the results obtained in this study show that
      these agents differ markedly in their ability to generate the active species
      MTIC.

PMID- 1998995
TI  - Instability of the anticancer agent etoposide under in vitro culture conditions.
AB  - Degradation of etoposide is rapid under in vitro culture conditions. At pH 7.4
      and 37 degrees C, the isomerisation of trans-etoposide to the inactive compound
      cis-etoposide has a half-life of 2 days in Dulbecco's modified Eagle's medium and
      results in the loss of 90% of the active drug within 1 week. As a consequence,
      prolonged incubations with etoposide in in vitro assays may lead to erroneous
      interpretations ignoring the real in vitro situation. The degradation is not
      influenced by organic compounds such as bovine serum albumin or amino acids but
      depends strongly on the pH value and, to a lesser degree, on the ionic strength
      of the medium. Therefore, we propose a mathematical correction based on the pH
      value so as to obtain the real exposure of cells to trans-etoposide during in
      vitro assays.

PMID- 1998994
TI  - Intratumoural administration of cisplatin in slow-release devices: II.
      Pharmacokinetics and intratumoural distribution.
AB  - The pharmacokinetics of cisplatin in mice with s.c. RIF 1 tumours was studied
      after intratumoural (i.t.) administration of drug in solution and in different
      slow-release devices. The data were compared with those obtained after i.p.
      administration of cisplatin. The slow-release devices under test were
      manufactured from either starch (ST) or polymeric hydrogels with different water
      uptakes (named T1, T2 and T3). In vitro release from these devices was
      approximately 100% in 2 h for starch rods, 100% in 24 h for T3 hydrogels, 45% in
      4 days for T2 hydrogels and less than 10% in 4 days for T1 hydrogels. In vivo
      release rates agreed well with the in vitro data for T1 and T2 rods and were
      slightly slower in vivo for the T3 rods. The ST rods released the drug 6 times
      slower in vivo than in vitro. Plasma concentrations after i.t. administration
      were lower than those measured after i.p. administration. Systemic exposure to
      both total and free platinum was reduced to 70% for i.t. as compared with i.p.
      administration. Tumour concentrations were 4 times higher after i.t. than after
      i.p. administration. Tumour and peak plasma levels of platinum increased with
      increasing release rates. With the faster-releasing formulations (ST and T3),
      tumour platinum concentrations were 100 times higher than after i.p.
      administration. With the slower releasing formulations (T1 and T2), total tumour
      platinum concentrations were 2 and 9 times higher, respectively, than after i.t.
      administration of cisplatin in solution. Platinum distribution within the tumour
      was homogeneous after i.p. administration. After i.t. administration of cisplatin
      in solution, platinum concentrations in the centre of the tumour were
      approximately 4 times higher than in peripheral tumour tissue. Implantation of
      cisplatin in T2 and T3 hydrogel rods resulted in large concentrations of platinum
      in the centre of the tumour (the site of implant), which decreased steeply
      towards the tumour periphery. In summary, i.t. administration of cisplatin
      solution produced better results than did systemic (i.p.) administration in terms
      of tumour versus plasma drug-concentration ratios. Administration of drug in slow
      release rods proved even more advantageous, although this was offset by
      inhomogeneous drug distributions within the tumour.

PMID- 1998996
TI  - High-dose 1,2,4-triglycidylurazol given in regimens preparatory to bone marrow
      transplantation. A preclinical pharmacology study.
AB  - To elucidate its potential role in the framework of bone marrow transplantation,
      we studied the toxicologic and pharmacologic properties of high doses of the
      triepoxide derivate 1,2,4-triglycidylurazol (TGU) in a preclinical dog model.
      Dose-dependent and dose-limiting gastrointestinal toxicity occurred in a dose
      range between 40 and 75 mg/kg, with the lethal dose for 50% of animals (LD50)
      being estimated at 60 mg/kg. Severe and life-threatening hematologic toxicity
      developed at all dose levels examined but was generally reversible. The
      combination of TGU and total-body irradiation produced synergistic
      gastrointestinal toxicity, necessitating reductions of the TGU dose by 50% as
      compared with the single-agent dose. In contrast, the combination of TGU and high
      dose busulfan resulted in no apparent nonhematologic synergistic toxicities. The
      immunosuppressive properties of TGU given in this combination enabled sustained
      histocompatible allogeneic marrow engraftment in three of four animals. The
      pharmacokinetics of TGU were not influenced by prior total-body irradiation or
      high-dose busulfan. We conclude that the myelotoxic, pharmacologic and
      immunosuppressive properties of high-dose TGU observed in this preclinical model
      seem to render the drug particularly suitable for use in regimens preparatory to
      bone marrow transplantation.

PMID- 1998997
TI  - Kinetics of melphalan leakage during hyperthermic isolation perfusion in melanoma
      of the limb.
AB  - The kinetics of melphalan leakage into the peripheral blood were studied in 21
      patients undergoing hyperthermic isolation perfusion of the upper or lower limb
      as an adjuvant treatment in high-risk melanoma; in 5 patients cisplatin was
      added. The melphalan concentrations in the peripheral blood rose predominantly
      during the first 20 min of perfusion and levelled out to an apparent steady state
      of about 0.28 micrograms/ml in upper extremity perfusions, and 0.34 (without
      cisplatin) and 0.37 micrograms/ml (with cisplatin) in lower extremity perfusion.
      Erythrocytes labelled with technetium Tc 99m, which were added concomitantly with
      melphalan to the perfusion medium, appeared in the systemic circulation of the
      patients at an almost constant rate of 0.32% (lower and upper limb perfusions
      without cisplatin and 0.37% (with cisplatin) of total tracer/min. This perfusate
      flow rate indicated by labelled erythrocytes completely explained the leakage of
      melphalan from the perfusion circuit into the peripheral blood. Peak
      concentrations of melphalan in the peripheral blood were observed immediately
      after reconstitution of normal hemodynamic conditions once isolation perfusion
      had been terminated. This fraction of melphalan might originate from tissue
      binding sites, but also from vascular compartments; therefore, a thorough washing
      out procedure might minimize this effect.

PMID- 1998998
TI  - Chemotherapy for early-stage gastrointestinal lymphoma.
AB  - A total of 176 patients with gastrointestinal lymphomas were reviewed. According
      to a modified staging classification, 51 of them had stage I/II disease and the
      remaining 125 had stage III/IV disease. In most cases (68%), the histology was
      intermediate-grade according to the NIH working formulation, and the B-cell
      immunophenotype was involved in 89% of the 45 cases with a known immunophenotype.
      The primary site was the stomach in 56% of cases and the bowel in 44%. A
      significantly higher proportion (P = 0.001) of those with bowel lymphomas had
      stage III/IV disease (88% vs 57%). The primary gastrointestinal lesion was
      resected in 122 patients, including all 51 cases of stage I/II disease. In all, 8
      stage I/II patients were given radiotherapy alone following surgery and the other
      43 underwent chemotherapy; of the latter, 19 received additional radiotherapy
      following chemotherapy. Chemotherapy was also given to 112 stage III/IV patients,
      42 of whom underwent additional radiotherapy. Factors associated with a poorer
      prognosis included advanced disease, bowel lymphoma and advanced age. Although
      the complete response (CR) rate according to disease stage was similar, stage
      I/II patients receiving chemotherapy showed a significantly lower relapse rate,
      better disease-free survival following CR and improved survival as compared with
      those receiving radiotherapy alone. However, additional radiotherapy following
      chemotherapy did not further improve the clinical outcome.

PMID- 1998999
TI  - Carboplatin/etoposide as first-line chemotherapy in advanced ovarian carcinoma: a
      pilot study.
AB  - In a pilot study, 18 patients with advanced ovarian cancer were evaluated for
      tolerance and response to a combination treatment with a fixed dose of
      carboplatin (350 mg/m2 given i.v. on day 1) and escalated doses of etoposide (70
      130 mg/m2 daily given i.v. on days 1-3) as first-line chemotherapy. The maximum
      tolerated dose of etoposide was 130 mg/m2 when given i.v. on days 1-3 in
      combination with 350 mg/m2 carboplatin given i.v. every 4 weeks. At these dose
      levels, bone marrow toxicity was manageable and did not appear to be cumulative.
      In all, 12 objective responses, including 9 complete responses (CRs) and 3
      partial responses (PRs), were achieved in 18 patients; 6 of the 9 CRs were
      confirmed as pathological CRs by second-look surgery.

PMID- 1999000
TI  - High-dose epirubicin as primary chemotherapy in advanced breast carcinoma: a
      phase II study.
AB  - A total of 40 patients with metastatic breast cancer were treated with 120 mg/m2
      i.v. epirubicin every 3 weeks for a maximum of 10 cycles. Nine achieved a
      complete response and 17 showed a partial response, for an objective response
      rate of 65% (95% confidence interval, 47%-83%); the median duration of response
      was 7 months (range, 1-15 months) and median survival amounted to 13 months
      (range, 2-20 months). Leucopenia (grade 2 or 3) was seen in 14 patients on day 21
      of the cycle. A subset of nine patients underwent blood counts on day 10, when
      all had marked neutropenia (less than 1 x 10(9)/l). Other toxicity was frequent
      and included nausea/vomiting (80%), alopecia (95%) and stomatitis (35%). Five
      patients showed a significant fall in cardiac output, but this reverted to normal
      after treatment. Epirubicin should have a role in the development of high-dose
      regimens for the treatment of advanced breast cancer.

PMID- 1999001
TI  - Pharmacokinetics of continuous-infusion amsacrine and teniposide for the
      treatment of relapsed childhood acute nonlymphocytic leukemia.
AB  - The systemic disposition of both amsacrine and teniposide was determined in
      children receiving treatment for resistant acute nonlymphocytic leukemia. As part
      of a phase I-II study, amsacrine and teniposide were given as continuous 72-h
      i.v. infusions at doses of 75-150 and 150-250 mg m-2 day-1, respectively. Plasma
      samples obtained during steady state were analyzed for drug concentrations by
      high-performance liquid chromatography assays specific for each compound.
      Clearance and systemic exposure values for both amsacrine and teniposide were
      calculated for 14 patients, and data were available for teniposide alone in an
      additional 14 subjects. Interpatient variability in clearance was substantial for
      each drug, producing overlapping systemic exposure across dose levels. No
      evidence of dose-dependent drug clearance was evident. Clearance values for
      teniposide given in combination with amsacrine were similar to previous values
      obtained when teniposide was given in an identical manner but as a single agent.
      In all, 80% of patients experienced some degree of mucositis after chemotherapy
      administration. Severe mucositis (Pediatric Oncology Group grades 3-4) occurred
      in 18% of cases, all of whom showed teniposide steady-state plasma concentrations
      above the median population value (11.9 micrograms/ml; P less than 0.0001). A
      comparison of the results of the present study on teniposide combined with
      amsacrine with those previously obtained for single-agent teniposide suggest that
      amsacrine produced little additive gastrointestinal toxicity. The evaluation of
      anti-cancer drug pharmacokinetics in individual patients during combination
      chemotherapy regimens helps to determine the relative importance of each agent
      when toxicity patterns are similar.

PMID- 1999002
TI  - Steady-state hydroxyflutamide plasma levels after the administration of two
      dosage forms of flutamide.
AB  - A bioavailability study of randomized cross-over design was carried out in eight
      volunteers who were given a 48-h flutamide treatment consisting of 250-mg tablets
      three times daily or 400-mg sustained-release tablets twice daily, followed 3
      weeks later by the alternative dosage form. Just before the last dose and 15
      times during the subsequent 24 h, blood samples were obtained for the
      determination of plasma hydroxyflutamide (the active metabolite of flutamide)
      levels by high-performance liquid chromatography. No statistically significant
      differences between the two dosage forms were found for the lag time, rate of
      initial increase in concentration, peak plasma concentration, mean
      hydroxyflutamide concentration within one dosing interval or 24-h AUC value. One
      subject presented mild and transient nausea during both treatment periods. After
      the first treatment period (250-mg tablets), an increase in serum bilirubin was
      observed in another volunteer, who was withdrawn from the study. It may be
      concluded that both dosage forms were bioequivalent.

PMID- 1999003
TI  - Pharmacokinetics of recombinant interferon alpha-C.
AB  - Recombinant interferon alpha-C (rIFN alpha-C, Interpharm), is a new type of alpha
      interferon that has a specific activity of 1-2 x 10(9) units/mg protein. The
      pharmacokinetics of rIFN alpha-C were studied in 11 patients with metastatic
      renal-cell carcinoma. A total of 10 million units IFN alpha-C were injected
      intramuscularly and the serum level of IFN was evaluated up to 72 h post
      administration. Measurable IFN concentrations appeared in the serum as early as
      0.5 h, and levels peaked at 4-6 h (Cmax = 53.2 +/- 4.6 units/ml). Relatively high
      levels persisted for 24 h and declined thereafter with an apparent half-life of 3
      4 h. The mean area under the serum-concentration curve (AUC) was 1,259 +/- 145
      units h ml-1, indicating good bioavailability of the preparation from the
      intramuscular injection.

PMID- 1999004
TI  - Carboplatin activity in untreated metastatic breast cancer patients--results of a
      phase II study.
AB  - Due to the favourable results previously obtained with cisplatin in breast cancer
      (54% response rate), we studied a second-generation platinum analogue,
      carboplatin, in patients with previously untreated breast cancer. A total of 20
      patients were entered in the study and all were evaluable. The median age was 57
      years and all patients were in menopause. Karnofsky scores of 80-100 and 40-70
      were registered in 14 and 6 cases, respectively. The predominant metastatic site
      was soft tissue in 12 subjects, visceral organs in 5 and bone in 3; 14 patients
      had greater than 2 metastatic sites. Carboplatin was given i.v. at a dose of 400
      mg/m2 on day 1, with a 3-week rest period. In 13 patients who did not respond or
      whose disease recurred after carboplatin treatment, the CMFVP, CAP or FAC regimen
      was given as second line treatment. Carboplatin activity was observed in 4
      patients [2 complete remissions (CRs) and 2 partial responses (PRs)], for a
      response rate of 20% (4/20); the 2 PRs were observed in soft tissue and bone and
      the 2 CRs, in lung, liver and bone. Remission lasted 2-10 months (mean, 4
      months). CMFVP given as second-line chemotherapy to 13 patients produced 7 PRs
      (7/13, 54%). Toxicity was moderate, producing no drug-related deaths. Anemia
      (grade I-II) was recorded in seven patients; grade I-II leukopenia, in six; and
      grade III-IV leukopenia in two (median leukocyte nadir, 1,600/mm3).
      Thrombocytopenia was observed in three cases (grades I, II and III; median
      platelet nadir, 47,800/mm3). Unpleasant nausea/vomiting was pronounced (12 cases
      of grade III-IV) in 19 subjects. There were no cases of neuro- or nephrotoxicity.
      Due to permanent myelosuppression, no more than five cycles could be given. Our
      study showed that, unlike cisplatin, carboplatin given at a dose of 400 mg/m2 has
      low antitumorigenic activity in breast cancer patients and produces pronounced
      myelotoxicity. Additional first-line chemotherapy studies using carboplatin are
      needed to define the antitumorigenic activity of this platinum analogue.

PMID- 1999005
TI  - Effect of verapamil on daunorubicin accumulation in lymphocytes isolated from
      patients undergoing chemotherapy.
AB  - Verapamil was shown to be capable of increasing intracellular daunorubicin levels
      in normal lymphocytes isolated from patients undergoing chemotherapy for
      epithelial ovarian cancer. The extent of the increase in daunorubicin
      accumulation was variable, occurring in the range of 0-123% as compared with
      intracellular daunorubicin levels attained in the absence of verapamil. No
      similar effect was seen in lymphocytes isolated from healthy volunteers. A
      tentative explanation of these data may be the induction of multidrug resistance
      (mdr)-like characteristics in normal lymphocytes following cytotoxic
      chemotherapy.

PMID- 1999006
TI  - Myocardial infarct size-limiting effect of ischemic preconditioning was not
      attenuated by oxygen free-radical scavengers in the rabbit.
AB  - BACKGROUND: The limiting effect of ischemic preconditioning on infarct size has
      been reported in canine hearts, which contain considerable amounts of xanthine
      oxidase, a free radical-producing enzyme. Furthermore, a recent study suggested
      that free radicals generated during preconditioning may contribute to the
      cardioprotective effect of preconditioning. The present study examined 1) whether
      preconditioning limits infarct size in rabbits, which, like humans, lack
      myocardial xanthine oxidase and 2) whether the cardioprotective effect of PC is
      mediated by free radicals. METHODS AND RESULTS: A branch of the circumflex
      coronary artery in rabbits was occluded for 30 minutes and then reperfused for 72
      hours. Myocardial infarct size and area at risk were determined by histology and
      fluorescent particles, respectively. Five groups were studied: an untreated
      control group, a preconditioned group (PC group), a high-dose superoxide
      dismutase (SOD)-treated preconditioned group (high-dose SOD-PC group), a low-dose
      SOD-treated preconditioned group (low-dose SOD-PC group), and a SOD-plus-catalase
      treated preconditioned group (SOD/CAT-PC group). Preconditioning was performed
      with four episodes of 5 minutes of ischemia and 5 minutes of reperfusion. The
      free radical scavengers (30,000 units/kg SOD for high-dose SOD-PC group, 15,000
      units/kg SOD for low-dose SOD-PC group, and 30,000 units/kg SOD plus 55,000
      units/kg catalase for SOD/CAT-PC group) were infused intravenously over 60
      minutes starting 20 minutes before preconditioning. Infarct size as the
      percentage of area at risk was 45.1 +/- 3.5% (mean +/- SEM) in the control group
      (n = 11), 13.3 +/- 3.0% in the PC group (n = 12), 9.7 +/- 1.8% in the high-dose
      SOD-PC group (n = 8), 11.9 +/- 2.2% in the low-dose SOD-PC group (n = 6), and 9.6
      +/- 2.3% in the SOD/CAT-PC group (n = 6) (p less than 0.05 versus control for the
      last four values). The differences in infarct size as the percent of area at risk
      among the PC, high-dose SOD-PC, low-dose SOD-PC, and SOD/CAT-PC groups were not
      significant. CONCLUSION: Ischemic preconditioning delays ischemic myocardial
      necrosis regardless of myocardial xanthine oxidase content. Free radicals are
      unlikely to have a major role in the mechanism of the preconditioning in rabbits.

PMID- 1999007
TI  - Transvascular intracardiac applications of a miniaturized phased-array ultrasonic
      endoscope. Initial experience with intracardiac imaging in piglets.
AB  - BACKGROUND: Recent advances in miniaturization of phased-array and mechanical
      ultrasound devices have resulted in exploration of alternative approaches to
      cardiac and vascular imaging in the form of transesophageal or intravascular
      imaging. Preliminary efforts in adapting phased-array endoscopes designed for
      transesophageal use to a transvascular approach have used full-sized phased-array
      devices introduced directly into the right atrium in open-chested animals. The
      purpose of this study was to assess the feasibility of using a custom-made, very
      small phased-array endoscope for intracardiac imaging introduced intravascularly
      through a jugular venous approach in young piglets. METHODS AND RESULTS:
      Experimental atrial septal defects created in four piglets (3-4 weeks old) had
      been closed with a buttoned atrial septal defect closure device consisting of an
      occluder in the left atrium and a counteroccluder in the right atrium. Five to 15
      days after atrial septal defect closure, the piglets were returned to the
      experimental laboratory, where a 6.3-mm, 17-element, 5-MHz phased-array probe
      mounted on a 4-mm endoscope was introduced through a cutdown incision of the
      external jugular vein and advanced to the right atrium. From the right atrium all
      four cardiac chambers, their inflows and outflows, and all four valves were well
      imaged with minimal superior and inferior rotation. High-resolution imaging of
      the atrial septum defined with anatomical accuracy, later verified by autopsy,
      the exact placement of both the occluder and counteroccluder in the left and
      right sides of the atrial septal defects and the absence of any shunting across
      the atrial septum in any of the four animals. CONCLUSIONS: Our efforts indicate
      that transvascular passage of small phased-array probes can be easily
      accomplished and is a promising technique for detailed visualization of cardiac
      structures. This approach may provide an alternative to transesophageal
      echocardiography, particularly for guiding interventional procedures such as
      placement of transcatheter closure devices in pediatric patients.

PMID- 1999008
TI  - Contractility and stiffness of noninfarcted myocardium after coronary ligation in
      rats. Effects of chronic angiotensin converting enzyme inhibition.
AB  - BACKGROUND: Previous studies have shown that global left ventricular function is
      depressed after myocardial infarction. However, little is known about the effects
      of myocardial infarction on contractility and the passive-elastic properties of
      residual myocardium. METHODS AND RESULTS: We evaluated isometric function and
      passive myocardial stiffness in isolated, noninfarcted left ventricular papillary
      muscle from rats 6 weeks after sham operation or myocardial infarction. Maximal
      developed tension and peak rate of tension rise (+dT/dt) were significantly
      decreased in untreated rats with large myocardial infarction compared with
      controls (3.3 +/- 1.1 versus 4.3 +/- 0.6 g/mm2 and 49.5 +/- 17.5 versus 72.5 +/-
      10.5 g/mm2/sec, respectively). Time to peak tension was prolonged (120 +/- 8
      versus 102 +/- 4 msec) and myocardial stiffness was increased in untreated
      myocardial infarction rats compared with controls (35.2 +/- 4.9 versus 24.2 +/-
      3.7). Rats with smaller myocardial infarctions differed from controls only with
      respect to a prolongation of time to peak tension. Papillary muscle myocyte cross
      sectional area was increased by 44% (p less than 0.05), and myocardial
      hydroxyproline content was increased by 160% (p less than 0.05) in rats with
      large myocardial infarctions compared with controls. To determine whether
      treatment that improves left ventricular function after myocardial infarction
      also improves myocardial function, rats were treated with captopril beginning 3
      weeks after myocardial infarction and continuing for 3 weeks. Treatment with
      captopril attenuated the prolongation in time to peak tension in the myocardial
      infarction rats; however, developed tension, +dT/dt, and muscle stiffness
      remained abnormal. Compared with untreated myocardial infarction rats, captopril
      treated myocardial infarction rats had a 9% decrease in myocyte cross-sectional
      area (p = 0.1) but a persistent increase in myocardial collagen content. In
      summary, large myocardial infarction in rats causes contractile dysfunction,
      increased stiffness, myocyte hypertrophy, and increased collagen content in the
      residual noninfarcted myocardium. Treatment with captopril alters the process of
      cardiac remodeling and hypertrophy and improves one parameter of contractility in
      noninfarcted myocardium; however, myocardial collagen content and myocardial
      stiffness remain abnormal. CONCLUSIONS: These findings suggest that angiotensin
      converting enzyme inhibition in the rat infarct model of heart failure improves
      global cardiac performance via combined effects on myocardial function and the
      peripheral circulation.

PMID- 1999009
TI  - Arginine restores cholinergic relaxation of hypercholesterolemic rabbit thoracic
      aorta.
AB  - BACKGROUND: Reduced synthesis of endothelium-derived relaxing factor (EDRF) may
      explain impaired endothelium-dependent vasodilation in hypercholesterolemia.
      Accordingly, we designed studies to determine if endothelium-dependent relaxation
      in hypercholesterolemic rabbits may be restored by supplying L-arginine, the
      precursor of EDRF. METHODS AND RESULTS: Normal or hypercholesterolemic rabbits
      received intravenous L-arginine (10 mg/kg/min) or vehicle for 70 minutes.
      Subsequently, animals were killed, thoracic aortas were harvested, and vascular
      rings were studied in vitro. Rings were contracted by norepinephrine and relaxed
      by acetylcholine chloride or sodium nitroprusside. Vasorelaxation was quantified
      by determining the maximal response (expressed as percent relaxation of the
      contraction) and the ED50 (dose of drug inducing 50% relaxation; expressed as 
      log M). In vessels from hypercholesterolemic animals receiving vehicle, there was
      a fivefold rightward shift in sensitivity to acetylcholine compared with normal
      animals (p = 0.05, n = 5 in each group). In vessels from hypercholesterolemic
      animals, L-arginine augmented the maximal response to acetylcholine (83 +/- 16%
      versus 60 +/- 15%, p = 0.04 versus vehicle) and increased the sensitivity to
      acetylcholine (ED50 value: 6.7 +/- 0.2 versus 6.2 +/- 0.2, p less than 0.05
      versus vehicle). Arginine did not affect maximal and EC50 responses to
      acetylcholine in vessels from normal animals. Arginine did not potentiate
      endothelium-independent responses in either group. CONCLUSIONS: We conclude that
      the endothelium-dependent relaxation is normalized in hypercholesterolemic rabbit
      thoracic aorta by in vivo exposure to L-arginine, the precursor for EDRF.

PMID- 1999010
TI  - Myocardial perfusion-contraction matching. Implications for coronary heart
      disease and hibernation.
AB  - Experimental studies demonstrate that short-term regional perfusion-contraction
      matching, in which the energy demands of regional myocardial contraction are
      reduced to match the diminished myocardial substrate supply, occurs during states
      of low coronary blood flow under resting conditions and during exercise-induced
      ischemia. This phenomenon is rapidly reversible and appears to occur in several
      clinical settings. Sustained perfusion-contraction matching is observed in states
      of partial experimental ischemia of intermediate duration lasting several hours.
      This condition might be called short-term hibernation and resembles clinical
      conditions such as unstable angina pectoris or myocardial infarction with some
      residual perfusion in which the contractile defect can be improved by reperfusion
      provided the ischemia is not severe enough to cause transmural necrosis. Such
      experimental and clinical observations may or may not relate to the setting of
      regional dysfunction at rest in patients with chronic coronary heart disease, in
      whom manifestations of acute ischemia may be absent but improvement of wall
      motion abnormalities occurs after CABG or balloon angioplasty. This condition may
      constitute the hypothetical state of chronic myocardial hibernation, for which
      tentative evidence exists from metabolic and perfusion studies using PET. Whether
      such a condition of prolonged perfusion-contraction matching might be associated
      with adaptive processes that could allow its persistence for long periods without
      manifest ischemia remains to be investigated.

PMID- 1999011
TI  - Coronary collaterals revisited. Accessory pathway to myocardial preservation
      during infarction.

PMID- 1999012
TI  - Late benefit of coronary surgery on mortality from myocardial infarction.

PMID- 1999013
TI  - Electrophysiological testing after myocardial infarction. A paradigm for
      assessing the incremental value of a diagnostic test.

PMID- 1999014
TI  - Laser angioplasty: a plea for modesty in the search for a real beginning.

PMID- 1999015
TI  - The bantamweight right ventricle and the Fontan operation. One-two-three and the
      right ventricle is out ... maybe.

PMID- 1999016
TI  - Hemostatic risk factors for coronary heart disease.

PMID- 1999017
TI  - Screening for latent coronary artery disease by exercise testing.

PMID- 1999018
TI  - Serum protein measurements and the diagnosis of acute myocardial infarction.

PMID- 1999019
TI  - Distinct forms of myocarditis.

PMID- 1999020
TI  - Is iron sufficiency a risk factor in ischemic heart disease?

PMID- 1999021
TI  - Adjuvant antiplatelet strategies in coronary thrombolysis.

PMID- 1999022
TI  - Reversal of hypercholesterolemia-induced endothelial dysfunction by L-arginine.

PMID- 1999023
TI  - Administration of endothelin-1 in humans.

PMID- 1999024
TI  - ACC/AHA guidelines and indications for coronary artery bypass graft surgery. A
      report of the American College of Cardiology/American Heart Association Task
      Force on Assessment of Diagnostic and Therapeutic Cardiovascular Procedures
      (Subcommittee on Coronary Artery Bypass Graft Surgery).

PMID- 1999025
TI  - Ten-year incidence of myocardial infarction and prognosis after infarction.
      Department of Veterans Affairs Cooperative Study of Coronary Artery Bypass
      Surgery.
AB  - BACKGROUND: The 10-year incidence of myocardial infarction (fatal and nonfatal)
      and the prognosis after infarction were evaluated in 686 patients with stable
      angina who were randomly assigned to medical or surgical treatment in the
      Veterans Administration Cooperative Study of Coronary Artery Bypass Surgery.
      METHODS AND RESULTS: Myocardial infarction was defined by either new Q wave
      findings or clinical symptoms compatible with myocardial infarction accompanied
      by serum enzyme elevations with or without electrocardiographic findings.
      Treatment comparisons were made according to original treatment assignment; 35%
      of the medical cohort had bypass surgery during the 10-year follow-up period. The
      overall cumulative infarction rate was somewhat higher in patients assigned to
      surgery (36%) than in medical patients (31%) (p = 0.13) due to perioperative
      infarctions (13%) and an accelerated infarction rate after the fifth year of
      follow-up (average, 2.4%/yr in the surgical group versus 1.4%/yr in the medical
      group). The 10-year cumulative incidence of death or myocardial infarction was
      also higher in surgical (54%) than in medical (49%) patients (p = 0.20).
      According to the Cox model, the estimated risk of death after infarction was 59%
      lower in surgical than in medical patients (p less than 0.0001). The reduction in
      postinfarction mortality with surgery was most striking in the first month after
      the event: 99% in the first month (p less than 0.0001) and 49% subsequently (p
      less than 0.0001). The estimated risk of death in the absence of infarction was
      nearly identical regardless of treatment (p = 0.75). Exclusion of perioperative
      infarctions did not alter the findings. CONCLUSIONS: Although surgery does not
      reduce the incidence of myocardial infarction overall, it does reduce the risk of
      mortality after infarction, particularly in the first 30 days after the event
      (fatal infarctions).

PMID- 1999026
TI  - What is the best predictor of spontaneous ventricular tachycardia and sudden
      death after myocardial infarction?
AB  - BACKGROUND: Death during the first year after myocardial infarction is most
      commonly due to spontaneous ventricular tachycardia (VT) or fibrillation (VF).
      The purpose of this study was to compare, in a single cohort of patients, the
      values of inducible VT, delayed ventricular activation, low left ventricular
      ejection fraction, high-grade ventricular ectopy, and ST segment displacement on
      exercise in predicting electrical events (witnessed instantaneous death and
      spontaneous VT or VF) during the first year after myocardial infarction. METHODS
      AND RESULTS: Three hundred sixty one patients aged less than 71 years underwent
      electrophysiological study, signal-averaged electrocardiogram, gated blood-pool
      scan, 24 hour ambulatory electrocardiographic monitoring, and exercise testing 1
      2 weeks after myocardial infarction and were then followed up for at least 1
      year. There were 34 deaths (eight witnessed instantaneous, 26 other), and nine
      patients survived one or more episodes of spontaneous VF or VT. Patients with
      inducible VT were 15.2 times more likely to suffer electrical events than
      patients without inducible VT. No proportional-hazards model excluding inducible
      VT was as good a predictor of electrical events as was inducible VT alone.
      CONCLUSIONS: Inducible VT at electrophysiological study was the single best
      predictor of spontaneous VT and sudden death after myocardial infarction.

PMID- 1999027
TI  - Prospective comparison of a conventional and an accelerated protocol for
      programmed ventricular stimulation in patients with coronary artery disease.
AB  - BACKGROUND: This study compared the sensitivity, specificity, and efficiency of a
      "conventional" and "accelerated" programmed stimulation protocol in 293 patients
      with coronary artery disease who had a history of sustained or nonsustained
      monomorphic ventricular tachycardia (VT). METHODS AND RESULTS: In the
      conventional protocol, one and two extrastimuli were introduced during sinus
      rhythm and during basic drive trains at cycle lengths of 600 and 400 msec at the
      right ventricular apex and then at the outflow tract or septum. In the
      accelerated protocol, one, two, and then three extrastimuli were introduced at
      each of three basic drive train cycle lengths (350, 400, and 600 msec) at the
      right ventricular apex; the procedure was repeated at a second right ventricular
      site. Six hundred thirty-four electrophysiological tests were performed using one
      of these two protocols either in the baseline state (293 tests) or during drug
      testing (341 tests). The yield of sustained, monomorphic VT was 89% with the
      conventional protocol and 92% with the accelerated protocol during baseline tests
      in patients who had a history of sustained VT (p = 0.05); 20% and 34%,
      respectively, during baseline tests in patients with a history of nonsustained VT
      (p = 0.06); and 70% and 77%, respectively, during drug testing (p = 0.2). To
      induce sustained, monomorphic VT, 10.1 +/- 5.0 (mean +/- SD) protocol steps and
      14.4 +/- 8.7 minutes were required with the conventional protocol, compared with
      4.0 +/- 3.7 steps and 5.6 +/- 6.1 minutes with the accelerated protocol (p less
      than 0.001 for each comparison). Among the tests in which sustained, monomorphic
      VT was induced, sustained polymorphic VT or ventricular fibrillation was induced
      more often with the conventional protocol (3.6%) than with the accelerated
      protocol (0.9%, p = 0.05). CONCLUSIONS: The efficiency of programmed stimulation
      can be improved by the early use of a basic drive train cycle length of 350 msec
      and three extrastimuli. Compared with a conventional stimulation protocol, the
      accelerated protocol used in this study reduces the number of protocol steps and
      duration of time required to induce monomorphic VT by an average of more than 50%
      and improves the specificity of programmed stimulation without impairing the
      yield of monomorphic VT.

PMID- 1999028
TI  - Interaction of neuropeptide Y and the sympathetic nervous system in vascular
      control in man.
AB  - BACKGROUND: There is increasing evidence that neuropeptide Y (NPY) contributes to
      the autonomic control of the circulation. NPY coexists with noradrenaline in
      perivascular nerve terminals, may be released during sympathetic stimulation, and
      is a potent constrictor of the human coronary circulation and other vascular
      beds. In vitro studies show that NPY can act either directly on vascular smooth
      muscle or indirectly by modulation of the presynaptic release or the postsynaptic
      actions of noradrenaline. It is unclear to what extent these mechanisms operate
      in vivo. METHODS AND RESULTS: The effect on forearm blood flow of intra-arterial
      NPY was studied in six volunteers during coinfusion of noradrenaline and during
      reflex sympathetic stimulation induced by lower-body negative pressure. NPY alone
      induced a dose-dependent reduction of forearm blood flow in all subjects studied,
      to a maximum of 49 +/- 6.1%. The reduction of flow during infusion of
      noradrenaline alone was 42 +/- 8%. The response to noradrenaline was unaffected
      by coinfusion of a threshold constrictor dose of NPY (50 pmol/min). Furthermore,
      the reflex sympathetic vasoconstrictor response to 20 cm H2O of lower-body
      negative pressure was similar in both the infused and control arms during the
      infusion of 50 pmol/min NPY. The response to noradrenaline was abolished by alpha
      blockade with phentolamine, but the flow reduction induced by NPY was unaffected
      by alpha-blockade. CONCLUSIONS: NPY is a potent constrictor of human forearm
      resistance vessels and has a direct effect independent of alpha-receptors. NPY
      has no detectable modulating effect in vivo on the action of endogenous or
      infused noradrenaline.

PMID- 1999029
TI  - Value of peak exercise oxygen consumption for optimal timing of cardiac
      transplantation in ambulatory patients with heart failure.
AB  - BACKGROUND: Optimal timing of cardiac transplantation in ambulatory patients with
      severe left ventricular dysfunction is often difficult. To determine whether
      measurement of peak oxygen consumption (VO2) during maximal exercise testing can
      be used to identify patients in whom transplantation can be safely deferred, we
      prospectively performed exercise testing on all ambulatory patients referred for
      transplant between October 1986 and December 1989. METHODS AND RESULTS: Patients
      were assigned into one of three groups on the basis of exercise data: Group 1 (n
      = 35) comprised patients accepted for transplant (VO2 less than or equal to 14
      ml/kg/min); group 2 (n = 52) comprised patients considered too well for
      transplant (VO2 greater than 14 ml/kg/min); and group 3 (n = 27) comprised
      patients with low VO2 rejected for transplant due to noncardiac problems. All
      three groups were comparable in New York Heart Association functional class,
      ejection fraction, and cardiac index (p = NS). Pulmonary capillary wedge pressure
      was significantly lower in group 2 than in either group 1 or 3 (p less than
      0.05), although there was wide overlap. Patients with preserved exercise capacity
      (group 2) had cumulative 1- and 2-year survival rates of 94% and 84%, which are
      equal to survival levels after transplantation. In contrast, patients rejected
      for transplant (group 3) had survival rates of only 47% at 1 year and 32% at 2
      years, whereas patients awaiting transplantation (group 1) had a survival rate of
      70% at 1 year (both p less than 0.005 versus patients with VO2 greater than 14
      ml/kg/min). All deaths in group 2 were sudden. By univariate and multivariate
      analyses, peak VO2 was the best predictor of survival, with only pulmonary
      capillary wedge pressure providing additional prognostic information.
      CONCLUSIONS: These data suggest that cardiac transplantation can be safely
      deferred in ambulatory patients with severe left ventricular dysfunction and peak
      exercise VO2 of more than 14 ml/min/kg.

PMID- 1999030
TI  - Results and follow-up after percutaneous pulsed laser-assisted balloon
      angioplasty guided by spectroscopy.
AB  - BACKGROUND: Few data are available on the long-term outcome of patients who
      undergo laser-assisted balloon angioplasty for recanalization of occluded
      peripheral arteries. Because the cost of laser angioplasty is high, the value of
      the method should be carefully analyzed before it can be considered a routine
      method for recanalization. The purpose of this study was to evaluate the early
      and late results of laser-assisted balloon angioplasty in patients who could not
      be recanalized by conventional techniques. METHODS AND RESULTS: Laser angioplasty
      was performed in 66 patients with total occlusion of the iliofemoral artery in
      whom mechanical techniques failed to recanalize the obstructed vessel. The system
      consisted of a pulsed dye laser operated at 480 nm, 2 microseconds/pulse, 5 Hz,
      50 mJ/pulse coupled into a 0.021-in. laser catheter. The treatment laser was
      connected with a diagnostic laser to induce tissue fluorescence for spectroscopic
      analysis via the same fiber. The treatment laser was emitted only when
      atheromatous tissue was recognized. After a pilot hole was created by laser
      emission, dilatation was performed to enlarge the channel. The mean length of
      occlusion was 8.8 +/- 6.1 cm. The primary success rate was 82%. It did not depend
      on the length of occlusion but was greater in non-calcified than in calcified
      lesions (88% versus 71%, p less than 0.03). Complications included seven early
      reocclusions that could be recanalized and eight perforations without clinical
      sequelae. At a mean 18-month follow-up, 64% of the laser-treated arteries
      remained patent. The rate of patency was related neither to the length of the
      occlusion nor to calcifications but was lower in patients who had early
      reocclusion (p less than 0.02). CONCLUSIONS: Pulsed dye laser-assisted balloon
      angioplasty is effective for recanalization of totally occluded arteries that
      cannot be treated by conventional means. The efficacy is limited by
      calcifications. The long-term patency rate is acceptable given the severity of
      the lesions.

PMID- 1999031
TI  - Prognostic significance of Doppler measures of diastolic function in cardiac
      amyloidosis. A Doppler echocardiography study.
AB  - BACKGROUND: We have previously characterized the left ventricular diastolic
      filling abnormalities in cardiac amyloidosis by Doppler methods. The various
      filling patterns were shown to be related to the degree of cardiac amyloid
      infiltration. The purpose of this study was to determine the value of Doppler
      diastolic filling variables for assessing prognosis in cardiac amyloidosis.
      METHODS AND RESULTS: We performed pulsed-wave Doppler studies of the left
      ventricular inflow and obtained clinical follow-up data in 63 consecutive
      patients with biopsy-proven systemic amyloidosis. All patients had typical
      echocardiographic features of cardiac involvement. The patients were subdivided
      into two groups according to deceleration time: Group 1 (33 patients) had a
      deceleration time of 150 msec or less, indicative of restrictive physiology, and
      group 2 (30 patients) had a deceleration time of more than 150 msec. Of the 63
      patients, 32 (51%) died during a mean follow-up period of 18 +/- 12 months. Of
      these deaths, 25 (78%) were cardiac deaths, and 19 of the 25 patients (76%) were
      from group 1. The 1-year probability of survival in group 1 was significantly
      less than that in group 2 (49% versus 92%, p less than 0.001). Bivariate analysis
      revealed that the combination of the Doppler variables of shortened deceleration
      time and increased early diastolic filling velocity to atrial filling velocity
      ratio were stronger predictors of cardiac death than were the two-dimensional
      echocardiographic variables of mean left ventricular wall thickness and
      fractional shortening. CONCLUSIONS: Doppler-derived left ventricular diastolic
      filling variables are important predictors of survival in cardiac amyloidosis.

PMID- 1999032
TI  - Safety of transesophageal echocardiography. A multicenter survey of 10,419
      examinations.
AB  - BACKGROUND: During the past few years, transesophageal echocardiography (TEE) has
      been increasingly used in clinical cardiology; data concerning the practicability
      and safety of the technique, however, are rare. METHODS AND RESULTS: This report
      analyzes the experience of 15 European centers performing TEE studies for at
      least 1 year. At the time of this survey, 10,419 TEE examinations had been
      attempted or performed in these institutions. These TEE examinations were carried
      out by 54 physicians, 53.7% of whom had been trained in endoscopic techniques.
      Within the same time period, 160,431 precordial echocardiographic examinations
      were performed in the 15 institutions; the ratio between TEE and transthoracic
      studies averaged 9.03 +/- 6.4% (range of the 15 centers, 1.4-23.6%). Of the
      10,419 patients, 9,240 (88.7%) were conscious inpatients or outpatients at the
      time of the TEE examination; the vast majority of the conscious patients did not
      receive intravenous sedation before TEE. In 201 cases (1.9%), insertion of the
      TEE probe was unsuccessfully attempted because of a lack of patient cooperation
      and/or operator experience (98.5%) or because of anatomical reasons (1.5%). In 90
      of 10,218 TEE studies (0.88%) with successful probe insertion, the examination
      had to be interrupted because of the patient's intolerance of the echoscope (65
      cases); because of pulmonary (eight cases), cardiac (eight cases), or bleeding
      complications (two cases); or for other reasons (seven cases). One of the
      bleeding complications resulted from a malignant lung tumor with esophageal
      infiltration and was fatal (mortality rate, 0.0098%). CONCLUSIONS: This
      multicenter survey documents that TEE studies are associated with an acceptable
      low risk when used by experienced operators under proper safety conditions.

PMID- 1999033
TI  - A quantitative analysis of hemodynamic effects of the right ventricle included in
      the circulation of the Fontan procedure.
AB  - BACKGROUND: Right heart hemodynamics were analyzed with a catheter-mounted
      velocity meter in seven patients after direct atrioventricular anastomosis for
      Fontan procedure (RV group) and were compared with those obtained in eight
      patients after direct atriopulmonary anastomosis (RA group). METHODS AND RESULTS:
      In the RV group, cardiac output was 2.7 +/- 0.6 l/min/m2; mean right atrial and
      pulmonary artery pressures were both 13 +/- 3 mm Hg; mean pulmonary artery wedge
      pressure was 7 +/- 5 mm Hg; left ventricular end-diastolic volume, determined
      angiographically, was 129 +/- 40% of normal; and its ejection fraction was 0.50
      +/- 0.09. In the RA group, data were similar to those of the RV group except that
      right heart pressure were lower in the RV group, which was related to the
      preoperative condition of the pulmonary circulation. In the RV group, the
      fraction of ventricular forward flow of the total forward flow in the main
      pulmonary artery ranged from 0.21 to 0.46 and was not correlated with cardiac
      output or with any other parameter. The backward flow into the inferior vena cava
      at ventricular systole was greater than the atrial flow in two patients in whom
      cardiac output was less than 2.2 l/min/m2, whereas caval backward flow at atrial
      contraction was greater than ventricular flow in the other five patients, of whom
      four had a cardiac output greater than 3.1 l/min/m2. CONCLUSIONS: We conclude
      that the inclusion of right ventricle in the circulation of the Fontan procedure
      does not necessarily improve overall hemodynamics in most patients.

PMID- 1999034
TI  - Catheter modification of the atrioventricular junction with radiofrequency energy
      for control of atrioventricular nodal reentry tachycardia.
AB  - BACKGROUND: The utility of transcatheter application of radiofrequency energy to
      eliminate atrioventricular nodal reentrant tachycardia (AVNRT) was investigated.
      METHODS AND RESULTS: Thirty-nine patients (mean age, 53 +/- 20 years; range 14-86
      years) with medically refractory AVNRT underwent perinodal ablation with
      radiofrequency energy. A custom-designed 6F catheter with a large (3-mm-long)
      distal electrode and interelectrode pacing of 2 mm was used in the majority of
      cases. The catheter used for ablation was initially positioned across the
      tricuspid anulus to obtain the largest His bundle electrogram, then withdrawn to
      obtain the largest atrial:ventricular electrogram ratio, with a small His bundle
      electrogram (less than or equal to 100 microV). Each application of
      radiofrequency energy (350-550 kHz, 16.2 +/- 5.2 W) was stopped after 60 seconds
      or if PR prolongation or an impedance rise was noted. The endpoints of the
      procedure were persistent modification of atrioventricular nodal conduction
      (either first-degree atrioventricular block or impairment of ventriculoatrial
      conduction) and noninducibility of AVNRT before and during isoproterenol
      administration. Radiofrequency energy was applied a mean of 6.8 +/- 3.5 times per
      session. After a mean follow-up of 8 +/- 3.0 months, 32 of the 39 patients (82%)
      have been free of AVNRT, and did not have high grade AV block. Three patients
      (8%) developed complete atrioventricular block and had pacemakers implanted. Two
      patients had unsuccessful initial procedures, and two patients had initially
      successful ablations but had recurrences of tachycardia 4-6 weeks later.
      Elimination of AVNRT appeared to be due to effects on the retrograde fast pathway
      in most patients. CONCLUSIONS: Radiofrequency ablation of the perinodal right
      atrium appears to be safe and effective for treatment of typical AVNRT:

PMID- 1999035
TI  - Fibrinogen, viscosity, and white blood cell count are major risk factors for
      ischemic heart disease. The Caerphilly and Speedwell collaborative heart disease
      studies.
AB  - BACKGROUND: Recent studies have suggested that hemostatic factors and white blood
      cell count are predictive of ischemic heart disease (IHD). The relations of
      fibrinogen, viscosity, and white blood cell count to the incidence of IHD in the
      Caerphilly and Speedwell prospective studies are described. METHODS AND RESULTS:
      The two studies have a common core protocol and are based on a combined cohort of
      4,860 middle-aged men from the general population. The first follow-up was at a
      nearly constant interval of 5.1 years in Caerphilly and 3.2 years in Speedwell;
      251 major IHD events had occurred. Age-adjusted relative odds of IHD for men in
      the top 20% of the distribution compared with the bottom 20% were 4.1 (95%
      confidence interval, 2.6-6.5) for fibrinogen, 4.5 (95% confidence interval, 2.8
      7.4) for viscosity, and 3.2 (95% confidence interval, 2.0-4.9) for white blood
      cell count. Associations with IHD were similar in men who had never smoked,
      exsmokers, and current smokers, and the results suggest that at least part of the
      effect of smoking on IHD is mediated through fibrinogen, viscosity, and white
      blood cell count. Multivariate analysis shows that white blood cell count is an
      independent risk factor for IHD as is either fibrinogen or viscosity, or possibly
      both. Jointly, these three variables significantly improve the fit of a logistic
      regression model containing all the main conventional risk factors. Further, a
      model including age, smoking habits, fibrinogen, viscosity, and white blood cell
      count predicts IHD as well as one in which the three hemostatic/rheological
      variables are replaced by total cholesterol, diastolic pressure, and body mass
      index. CONCLUSION: Jointly, fibrinogen, viscosity, and white blood cell count are
      important risk factors for IHD.

PMID- 1999036
TI  - Concept of maximal flow ratio for immediate evaluation of percutaneous
      transluminal coronary angioplasty result by videodensitometry.
AB  - BACKGROUND: In the setting of percutaneous transluminal coronary angioplasty
      (PTCA), immediate information about the result of the intervention is important,
      whereas morphological parameters are often less reliable than in diagnostic
      coronary arteriography. Recently, a new videodensitometric method was introduced
      and validated in animal experiments, which allows accurate comparison of maximal
      myocardial perfusion between situations with different degrees of stenosis. This
      method uses mean transit time (Tmn) of the contrast agent at maximal hyperemia as
      a parameter for maximal flow and is strictly in accordance with indicated
      dilation theory. METHODS AND RESULTS: In 40 patients with angina pectoris, single
      vessel disease, and a positive exercise test at the time of acceptance for PTCA,
      this approach was applied for evaluation of the improvement of maximal flow
      achieved by the PTCA. Maximal vasodilation was induced immediately before and 15
      minutes after PTCA by intracoronary administration of papaverine, and digital
      angiographic studies were performed. By special breath-holding instruction,
      almost motionless, triggered image acquisition was possible during 15-20
      heartbeats. Excellent subtraction images could be obtained, and reliable
      determination of Tmn at maximal hyperemia was possible in 33 patients both before
      and after PTCA. The ratio between maximal flow after and before PTCA, called
      maximal flow ratio (MFR), was represented by the ratio between Tmn before and
      after the intervention and compared with the results of exercise testing 24-48
      hours before and 7-10 days after the procedure. After correction for pressure
      changes, MFR was 2.2 +/- 1.5 for the 33 dilated vessels and 1.0 +/- 0.2 for 25
      normal vessels serving as a control. In 94% of all patients, an MFR value of more
      than 1.6 or less than 1.6 discriminated between presence or absence of reversal
      of exercise test result from positive to negative. If on-line judgment of success
      was based upon angiographic parameters or measurement of trans-stenotic pressure
      gradient, the relation with noninvasive functional improvement was present only
      in 66% and 74% of all patients, respectively. A definite range of what can be
      called normal Tmn at maximal hyperemia could be distinguished, and post-PTCA
      values for successfully dilated arteries returned completely to this normal
      range. CONCLUSIONS: Accurate comparison of maximal myocardial perfusion before
      and after PTCA is possible in man, improvement of maximal flow is highly related
      to functional improvement as indicated by exercise test results, and, therefore,
      this method provides a straightforward way for on-line evaluation of the result
      of the intervention.

PMID- 1999037
TI  - Heart rate adjustment of exercise-induced ST segment depression. Improved risk
      stratification in the Framingham Offspring Study.
AB  - BACKGROUND: Simple heart rate adjustment of ST segment depression during exercise
      (delta ST/HR index) and the pattern of ST depression as a function of heart rate
      during exercise and recovery (the rate-recovery loop) have been shown to improve
      the ability of the exercise electrocardiogram to detect the presence of coronary
      heart disease (CHD), but the performance of these methods for the prediction of
      future coronary events remains to be examined. METHODS AND RESULTS: We compared
      the delta ST/HR index and the rate-recovery loop with standard
      electrocardiographic criteria for prediction of CHD events in 3,168 asymptomatic
      men and women in the Framingham Offspring Study who underwent treadmill exercise
      electrocardiography and who, at entry, were free of clinical and
      electrocardiographic evidence of CHD. After a mean follow-up of 4.3 years, there
      were 65 new CHD events: four sudden deaths, 24 new myocardial infarctions, and 37
      incident cases of angina pectoris. When a Cox proportional hazards model with
      adjustment for age and sex was used, a positive exercise electrocardiogram by
      standard criteria (greater than or equal to 0.1 mV horizontal or downsloping ST
      segment depression) was not predictive of new CHD events (chi 2 = 0.40, p =
      0.52). In contrast, stratification according to the presence or absence of a
      positive delta ST/HR index (greater than or equal to 1.6 microV/beat/min) and a
      positive (counterclockwise) rate-recovery loop was associated with CHD event risk
      (chi 2 = 9.45, p less than 0.01) and separated subjects into three groups with
      varying risks of coronary events: high risk, when both tests were positive
      (relative risk 3.6; 95% confidence interval, 2.4-5.4); intermediate risk, when
      either the delta ST/HR index or the rate-recovery loop was positive (relative
      risk, 1.9; 95% confidence interval, 1.3-2.8); and low risk, when both tests were
      negative. After multivariate adjustment for age, sex, smoking, total cholesterol
      level, fasting glucose level, diastolic blood pressure, and electrocardiographic
      evidence of left ventricular hypertrophy, the combined delta ST/HR index and rate
      recovery loop criteria remained predictive of coronary events (chi 2 = 5.45, p =
      0.02). CONCLUSIONS: Heart rate adjustment of ST segment depression by the delta
      ST/HR index and the rate-recovery loop during exercise electrocardiography can
      improve prediction of future coronary events in asymptomatic men and women.

PMID- 1999038
TI  - Electrocardiographic body surface potential mapping in the Wolff-Parkinson-White
      syndrome. Noninvasive determination of the ventricular insertion sites of
      accessory atrioventricular connections.
AB  - BACKGROUND: A reliable, noninvasive procedure to determine the location of
      accessory atrioventricular connections in patients with Wolff-Parkinson-White
      syndrome would add an important diagnostic tool to the clinical armamentarium.
      METHODS AND RESULTS: Body surface potential mapping (BSPM) using 180 electrodes
      in various-sized vests and displayed as a calibrated color map was used to
      determine the ventricular insertion site of the accessory atrioventricular (AV)
      connections in 34 patients with Wolff-Parkinson-White syndrome. Attempts were
      made to determine the 17 ventricular insertion sites described by Guiraudon et
      al. All 34 patients had an electrophysiologic study (EPS) at cardiac
      catheterization, and 18 had surgery so the ventricular insertion sites could be
      accurately located using EPS at surgery. A number of physiologic observations
      were also made with BSPM. CONCLUSIONS: The following conclusions were drawn: 1)
      BSPM using QRS analysis accurately predicts the ventricular insertion site of
      accessory AV connections in the presence of a delta wave in the
      electrocardiogram; 2) the ventricular insertion sites of accessory AV connections
      determined by BSPM and by EPS at surgery were identical or within one mapping
      site (1.5 cm or less) in all but four of 18 cases; three of the four exceptions
      had more than one accessory AV connection, and the other had a very broad
      ventricular insertion; 3) BSPM and EPS locations of the accessory AV connections
      correlated very well in the 34 cases despite the fact that BSPM determines the
      ventricular insertion site and EPS determines the atrial insertion site of the
      accessory AV connection; 4) as suggested by the three cases of multiple accessory
      AV connections, EPS and BSPM may be complementary since BSPM identified one
      pathway and EPS identified the other (in the case with a broad ventricular
      insertion, BSPM and EPS demonstrated different proportions of that insertion); 5)
      BSPM using ST-T analysis is very much less accurate in predicting the ventricular
      insertion site of accessory AV connections unless there is marked preexcitation;
      6) standard electrocardiography using the Gallagher grid methodology (but with no
      attempt at stimulating maximal preexcitation) was not as accurate as QRS analysis
      of BSPM in predicting the ventricular insertion site of the accessory AV
      connection; however, exact comparison is hampered by the different number and
      size of the Gallagher and Guiraudon insertion sites; 7) BSPM using QRS analysis
      appears to be very accurate in predicting right ventricular versus left
      ventricular posteroseptal accessory AV connections; 8) typical epicardial right
      ventricular breakthrough, indicative of conduction via the specialized AV
      conduction system, occurs in all patients with left ventricular free wall
      accessory AV connections; 9) epicardial right ventricular breakthrough was not
      observed in cases with right ventricular free wall or anteroseptal accessory AV
      connections; 10) epicardial right ventricular breakthrough can occur in the
      presence of posteroseptal accessory AV connections, whether right or left
      ventricular; and 11) the delay in epicardial right ventricular breakthrough in
      cases with left ventricular insertion may provide a marker to estimate the degree
      of ventricular preexcitation.

PMID- 1999039
TI  - Diagnostic efficiency of troponin T measurements in acute myocardial infarction.
AB  - BACKGROUND: The present study was designed to evaluate the efficiency of a newly
      developed troponin T enzyme immunoassay for the detection of acute myocardial
      infarction. METHODS AND RESULTS: The study comprised 388 patients admitted with
      chest pain and suspected myocardial infarction and 101 patients with skeletal
      muscle damage and additional suspected myocardial cell damage. Troponin T was
      elevated to more than twice the analytical sensitivity of the assay (0.5
      microgram/l) in all patients with non-Q wave (range, 1.2-5 micrograms/l) and Q
      wave infarction (range, 3-220 micrograms/l). Troponin T appeared in serum as
      early as 3 hours after onset of pain in 50% of the patients and remained elevated
      in all patients for more than 130 hours, revealing release kinetics of both free
      cytosolic and structurally bound molecules. The diagnostic efficiency of troponin
      T was superior to that of creatine kinase-MB (98% versus 97%) and remained at 98%
      until 5.5 days after admission, if patients with unstable angina were excluded
      from analysis. In the 79 patients with unstable angina, troponin T was elevated
      (range, 0.55-3.1 micrograms/l) in at least one blood sample from each of 37
      patients (56%). Circulating troponin T was correlated to the presence of
      reversible ST segment or T wave changes on the electrocardiogram (p less than
      0.005) and to the frequency of in-hospital complications. In the 101 patients
      with skeletal muscle damage and suspected additional cardiac muscle damage,
      troponin T was the most useful test; its efficiency was 89% or 94% (depending on
      the discriminator value used) as compared with 63% for creatine kinase-MB.
      CONCLUSIONS: Thus, the data of the study indicate that the newly developed
      troponin T test improves the efficiency of serodiagnostic tools for the detection
      of myocardial cell necrosis as compared with conventionally used cardiac enzymes.

PMID- 1999040
TI  - Intravascular ultrasound imaging of human coronary arteries in vivo. Analysis of
      tissue characterizations with comparison to in vitro histological specimens.
AB  - BACKGROUND: Intravascular ultrasound imaging was performed in 27 patients after
      coronary balloon angioplasty to quantify the lumen and atheroma cross-sectional
      areas. METHODS AND RESULTS: A 20-MHz ultrasound catheter was inserted through a
      1.6-mm plastic introducer sheath across the dilated area to obtain real-time
      images at 30 times/sec. The ultrasound images distinguished the lumen from
      atheroma, calcification, and the muscular media. The presence of dissection
      between the media and the atheroma was well visualized. These observations of
      tissue characterization were compared with an in vitro study of 20 human
      atherosclerotic artery segments that correlated the ultrasound images to
      histological preparations. The results indicate that high-quality intravascular
      ultrasound images under controlled in vitro conditions can provide accurate
      microanatomic information about the histological characteristics of
      atherosclerotic plaques. Similar quality cross-sectional ultrasound images were
      also obtained in human coronary arteries in vivo. Quantitative analysis of the
      ultrasound images from the clinical studies revealed that the mean cross
      sectional lumen area after balloon angioplasty was 5.0 +/- 2.0 mm2. The mean
      residual atheroma area at the level of the prior dilatation was 8.7 +/- 3.4 mm2,
      which corresponded to 63% of the available arterial cross-sectional area. At the
      segments of the coronary artery that appeared angiographically normal, the
      ultrasound images demonstrated the presence of atheroma involving 4.7 +/- 3.2
      mm2, which was a mean of 35 +/- 23% of the available area bounded by the media.
      CONCLUSIONS: Intravascular ultrasound appears to be more sensitive than
      angiography for demonstrating the presence and extent of atherosclerosis and
      arterial calcification. Intracoronary imaging after balloon angioplasty reveals
      that a significant amount of atheroma is still present, which may partly explain
      why the incidence of restenosis is high after percutaneous transluminal coronary
      angioplasty.

PMID- 1999041
TI  - Acute coronary artery occlusion during and after percutaneous transluminal
      coronary angioplasty. Frequency, prediction, clinical course, management, and
      follow-up.
AB  - BACKGROUND: Acute coronary artery occlusion after percutaneous transluminal
      coronary angioplasty (PTCA) continues to remain a serious complication despite
      significant improvement in operator performance and technological advancements.
      This retrospective study was performed to ascertain the frequency, predictive
      variables, management, and outcome of acute coronary artery occlusion. METHODS
      AND RESULTS: The study was based on data from 1,423 consecutive patients who
      underwent an elective coronary angioplasty between January 1986 and December
      1988. Acute coronary artery occlusion occurred in 104 patients (7.3%). Acute
      occlusion developed during the dilatation procedure in 80 patients (5.6%) and
      within 24 hours after the procedure in 24 patients (1.7%). Four clinical and 14
      angiographic variables predictive for acute coronary artery occlusion were
      analyzed in these 104 patients with a complicated procedure and were compared
      with those in 104 representative patients with successful attempts. Multivariate
      analysis found three independent predictive variables: unstable angina,
      multivessel disease, and complex lesions. The overall clinical outcome after
      management of acute coronary artery occlusion including immediate repeat
      dilatation (95 patients), use of intracoronary streptokinase (34 patients), or
      autoperfusion catheter (12 patients) was successful (reduction of lumen diameter
      to less than 50%, no death, no myocardial infarction [MI], and no emergency
      surgery) in 42 patients (40%), was a failure without major complication in four
      patients (4%), and was a failure with major complication (death, MI, and
      emergency surgery) in 58 patients (56%). The overall mortality rate was 6% (six
      patients), the overall MI rate was 36% (37 patients), and emergency bypass
      surgery was required in 30% of patients (31 patients). At 6 months' follow-up of
      42 patients with successful management, recurrent angina pectoris due to
      restenosis occurred in 10 patients (24%), and a late MI occurred in one patient
      (3%). At 6 months' follow-up of 56 survivors with unsuccessful management
      (development of MI or need for emergency bypass surgery), recurrent angina
      occurred in nine patients (16%), and cardiac death in two patients (4%). However,
      the majority of patients in both groups were either symptom free or had mild
      angina pectoris. CONCLUSION: Acute coronary artery occlusion during PTCA is often
      unpredictable, but its frequency is higher in patients with unstable angina,
      multivessel disease, and complex lesions. Despite immediate redilatation, use of
      intracoronary streptokinase, and emergency bypass surgery, PTCA is associated
      with a high mortality and morbidity.

PMID- 1999042
TI  - Baroreflex sensitivity and electrophysiological correlates in patients after
      acute myocardial infarction.
AB  - BACKGROUND: Several studies have identified transient disturbances of autonomic
      function during the acute and recovery phases of myocardial infarction, and it
      has recently been suggested that survivors of acute myocardial infarction with
      depressed vagal tone may be at increased risk of sudden or arrhythmic death.
      METHODS AND RESULTS: To investigate this hypothesis, parasympathetic function was
      assessed by arterial baroreflex sensitivity (BRS) testing (using the
      phenylephrine method) and by heart rate variability (HRV) analysis from 24-hour
      Holter recording in 68 patients at day 7-10 after infarction. The relation
      between autonomic tone and markers of arrhythmic propensity, including programmed
      ventricular stimulation (PVS) and late potentials in addition to other clinical
      variables, was examined. BRS for the whole group was 7.0 +/- 4.7 msec/mm Hg and
      was inversely correlated with age (r = 0.53, p less than 0.001) but not with left
      ventricular ejection fraction (r = 0.035, p = NS). In those patients in whom
      sustained monomorphic ventricular tachycardia (SMVT) was induced, BRS was
      significantly reduced (p = 0.001) as was HRV (p = 0.007) and left ventricular
      ejection fraction (p = 0.022). The strongest association between any variable
      (including HRV, BRS, late potentials, left ventricular ejection fraction,
      exercise testing, Q waves, and infarct site) and the induction of sustained
      monomorphic ventricular tachycardia was depressed BRS with a relative risk of
      36.28 (95% confidence interval, 5-266). CONCLUSIONS: This study confirms that
      depressed BRS identifies a subgroup at high risk for arrhythmic events after
      myocardial infarction and that programmed ventricular stimulation may be safely
      limited to this group without any loss of predictive accuracy.

PMID- 1999043
TI  - Giant cell versus lymphocytic myocarditis. A comparison of their clinical
      features and long-term outcomes.
AB  - BACKGROUND: Giant cell myocarditis has rarely been diagnosed premortem, and
      little is known about its natural history. In addition, no comparative studies
      with lymphocytic myocarditis exist. METHODS AND RESULTS: The clinical features,
      serial change in left ventricular fraction (LVEF), and outcomes of all patients
      with histologically verified myocarditis were retrospectively evaluated. Ten
      patients (22%) were found to have giant cell myocarditis (group 1), whereas the
      remaining 36 (78%) had lymphocytic myocarditis (group 2). Age at presentation,
      gender distribution, duration of symptoms, initial LVEF, and resting hemodynamics
      did not differ between groups. Ventricular tachycardia was detected in 90% of
      group 1 patients compared with only 25% of group 2 (p = 0.0007). Atrioventricular
      block that required pacemaker insertion was also more common in group 1 (60%)
      than in group 2 (8.3%) (p = 0.001). Left ventricular systolic function declined
      during follow-up in group 1 patients (LVEF, 0.43 +/- 0.07-0.26 +/- 0.05, p =
      0.11) but increased in group 2 patients (LVEF, 0.33 +/- 0.03-0.41 +/- 0.03, p =
      0.02). When the net change between initial and final LVEF was assessed, a
      significant difference was evident (giant cell group, -0.17 +/- 0.06; lymphocytic
      group, +0.07 +/- 0.03; p = 0.0008). Although a greater proportion of patients in
      group 1 died or required transplantation (seven of 10 versus 11 of 36, p = 0.03),
      actuarial survival over 4 years was not different for the giant cell group (50%)
      than for the lymphocytic group (62%). CONCLUSION: Giant cell myocarditis was more
      prevalent than previously recognized and highly associated with both ventricular
      tachycardia and pacemaker requirement. The likelihood of an adverse event, either
      cardiovascular mortality or cardiac transplantation, was significantly greater
      for patients with giant cell myocarditis than for those with lymphocytic
      myocarditis, perhaps because of the progressive decline in left ventricular
      systolic function that was observed in those with giant cell myocarditis.

PMID- 1999044
TI  - Alterations in left ventricular diastolic twist mechanics during acute human
      cardiac allograft rejection.
AB  - BACKGROUND: Contraction of obliquely oriented left ventricular (LV) fibers
      results in a twisting motion of the left ventricle. The purpose of this study was
      to assess the effects of acute human cardiac allograft rejection on LV twist
      pattern and the twist-volume relation. METHODS AND RESULTS: Tantalum markers were
      implanted into the LV midwall in 15 transplant recipients to measure time
      varying, three-dimensional chamber twist using computer-assisted analysis of
      biplane cinefluoroscopic images. Twist was defined as the mean longitudinal
      gradient of circumferential rotation about the LV long axis. When plotted against
      normalized percent ejection fraction (%EF), the resulting twist-normalized %EF
      relation could be divided into three phases. In systole, LV twist was linearly
      related to ejection of blood. In contrast, diastolic untwist was characterized by
      early rapid recoil with little change in LV volume, followed by more gradual
      untwisting when the bulk of diastolic filling occurred. During 10 acute rejection
      episodes in 10 patients, maximum twist, peak systolic twist rate, and the slope
      of the systolic twist-normalized %EF relation did not change. In contrast, the
      slope of the early (first 15% of filling) diastolic twist-normalized %EF relation
      (M(early-dia)) decreased significantly (-0.194 +/- 0.062 [prerejection] versus 
      0.103 +/- 0.054 rad/cm [rejection], p = 0.0003), resulting in a prolonged tau 1/2
      (time required to untwist by 50% [20 +/- 5% versus 28 +/- 5% of diastole], p =
      0.0003) and decrease in percent untwisting at 15% diastolic LV filling (62 +/-
      11% versus 36 +/- 13%, p = 0.0003). Therefore, a greater proportion of LV
      untwisting occurred later in diastole during rejection, as reflected by an
      increase in the slope (M(mid-dia)) of the middle to late (from 15 to 90% filling)
      diastolic twist-normalized %EF relation (-0.018 +/- 0.009 versus -0.030 +/- 0.010
      rad/cm, p = 0.0015). Peak rate of untwist was not affected. With resolution of
      rejection, M(early-dia) and percent untwist during early diastole returned to
      baseline levels (p = NS versus baseline). There was also a trend for M(mid-dia)
      to return toward prerejection values (p = NS versus baseline), but this change
      did not reach statistical significance compared with rejection values.
      CONCLUSION: Acute cardiac allograft rejection is associated with altered
      diastolic twist mechanics in the absence of any demonstratable systolic
      abnormalities. During rejection, myocardial edema and other factors may result in
      intrinsic changes of the elastic properties of the myocardium, thereby leading to
      modification of recoil forces responsible for the early, rapid unwinding of the
      deformed ventricle.

PMID- 1999045
TI  - Measurement of regional myocardial blood flow with multiple colored microspheres.
AB  - BACKGROUND: The use of radioactive microspheres (RM) for the measurement of
      regional myocardial blood flow (RMBF) is limited and inaccessible to many
      investigators due to radiation safety concerns and radioactive waste disposal
      problems. Therefore, a new method for the measurement of RMBF using colored
      microspheres (CM) was developed. METHODS AND RESULTS: Polystyrene spheres
      (diameter, 15 +/- 0.1 [SD] micron; density, 1.09 g/ml) were dyed with one of five
      colors. With the injection of CM into the left atrium or into a coronary
      perfusion line, RMBF and its distribution can be determined. CM are extracted
      from the myocardium and blood by digestion with potassium hydroxide and
      subsequent microfiltration. The dyes are then recovered from the CM within a
      defined volume of a solvent, and their concentrations are determined by
      spectrophotometry. The separation of composite absorbance spectra by
      spectrophotometry with the CM technique was as good as the separation of energy
      spectra by a gamma-counter using the RM technique. Leaching of dye from the CM
      was less than 0.1% during a 2-month period in vitro. Significant leaching of dye
      from the microspheres also did not occur during 8 hours in the blood and
      myocardium of four anesthetized dogs in vivo. For further validation of this
      method, pairs of CM and RM (15.5 +/- 0.1 [SD] microns) were simultaneously
      injected under five different RMBF conditions (range, 0-10 ml/[min.g]) into the
      left anterior descending coronary artery of four anesthetized pigs, with coronary
      inflow as a flow reference, or into the left atrium of four anesthetized dogs
      using aortic blood withdrawal as a reference. The relation between RMBF
      determined by CM and RM was CM = 0.01 + 1.00.RM (r = 0.98, n = 1,080 data points)
      in the pigs, and CM = -0.19 + 0.92.RM (r = 0.97, n = 1,813 data points) in the
      dogs. CONCLUSIONS: Measurement of RMBF with CM yields values very similar to
      those of RM. Their use is less expensive and avoids all the disadvantages related
      to radioactivity, thus offering an alternative method for as many as five RMBF
      measurements in a single experiment.

PMID- 1999046
TI  - Multiplexing studies of effects of rapid atrial pacing on the area of slow
      conduction during atrial flutter in canine pericarditis model.
AB  - BACKGROUND: We report that rapid atrial pacing interrupts atrial flutter when the
      orthodromic wave front from the pacing impulse is blocked in an area of slow
      conduction in the reentry circuit. To characterize the area of slow conduction
      during atrial flutter and rapid pacing, we studied 11 episodes of induced atrial
      flutter, mean cycle length 157 +/- 20 msec, in eight dogs with sterile
      pericarditis. METHODS AND RESULTS: Atrial electrograms were recorded
      simultaneously from 95 pairs of right atrial electrodes during the interruption
      of atrial flutter by rapid atrial pacing, mean cycle length 139 +/- 21 msec.
      Areas of slow conduction during atrial flutter were demonstrated at one to three
      sites in the reentry circuit. After rapid pacing captured the reentry circuit,
      one area of slow conduction either disappeared (10 episodes) or the degree of
      slow conduction in an area of slow conduction decreased (one episode). Both
      changes were in association with activation of the region by a wave front from
      the pacing impulse that arrived from a direction different than that during the
      induced atrial flutter. Interruption of atrial flutter during rapid pacing
      occurred when the orthodromic wave front from the pacing impulse blocked in an
      area of slow conduction that had either newly evolved during rapid pacing (seven
      episodes) or that was previously present (four episodes). CONCLUSIONS: Areas of
      slow conduction present during atrial flutter and rapid pacing of atrial flutter
      are functional and depend on both the atrial rate and the direction of the
      circulating wave fronts. Interruption of atrial flutter by rapid pacing results
      from block of the orthodromic wave front of the pacing impulse in an area of slow
      conduction in the reentry circuit.

PMID- 1999048
TI  - Delayed visualization of the gallbladder with a rim sign. An unusual finding in
      chronic cholecystitis.
AB  - The rim sign of increased activity in the gallbladder fossa during nuclear
      hepatobiliary imaging has been described, with one exception, only in conjunction
      with a nonvisualizing gallbladder, and it strongly suggests acute complicated
      cholecystitis. A case is presented in which a rim sign was present despite later
      visualization of the gallbladder in presumed chronic cholecystitis.

PMID- 1999047
TI  - Xanthine oxidase inhibition does not limit canine infarct size.
AB  - BACKGROUND: Evidence supporting the role of xanthine oxidase in myocardial
      reperfusion injury is based on studies with pharmacological interventions used to
      inhibit enzyme function. Controversy exists, however, regarding the true role of
      xanthine oxidase in reperfusion injury. This study was performed to determine
      whether xanthine oxidase inhibition limits myocardial injury due to coronary
      artery occlusion and reperfusion. METHODS AND RESULTS: Anesthetized dogs
      underwent coronary artery occlusion (90 minutes) and reperfusion (6 hours).
      Oxypurinol (28 mg/kg) or amflutizole (30 mg/kg), chemically unrelated inhibitors
      of xanthine oxidase, or vehicle was infused intravenously 15 minutes before and 3
      hours after reperfusion. Regional myocardial blood flow was determined with
      radiolabeled microspheres. Infarct size was determined with the tetrazolium
      method. Myocardial infarct size (percent of risk region) was less in oxypurinol
      treated dogs, 32 +/- 16%, compared with that of the control group, 46 +/- 15%.
      Infarct size for the amflutizole-treated dogs, 40 +/- 21%, was not significantly
      different from that of the control group. There were no differences in rate
      pressure product or collateral blood flow to account for differences in infarct
      size. Uric acid concentration in the coronary venous plasma increased after
      reperfusion in the dogs treated with vehicle but not in the drug-treated dogs.
      Xanthine oxidase inhibition was demonstrated in each of the drug treatment
      groups, but only oxypurinol limited the extent of myocardial injury. CONCLUSIONS:
      Previously reported cardioprotective effects of allopurinol, noted to occur only
      when the drug was administered chronically, may be related to a property of
      oxypurinol, a major metabolite of allopurinol. The beneficial effect of
      oxypurinol is unrelated to inhibition of superoxide formation during xanthine
      oxidase-catalyzed oxidation of xanthine and hypoxanthine.

PMID- 1999050
TI  - Brain SPECT imaging with Tc-99m HMPAO in ophthalmoplegia plus.
AB  - In 14 patients with ophthalmoplegia plus Tc-99m hexamethylpropylene amineoxime
      (HMPAO) brain SPECT imaging was performed. Three patients showed bilateral
      parieto-occipital hypoperfusions, and two patients had left parietal defects (one
      with an additional right temporal lesion). Two patients presented with occipital
      hypoperfusions and one with a distinct hypoperfusion in the medial part of both
      frontal lobes. Hypoperfusion of the visual cortex might result from permanently
      decreased input from the degenerated retina. The hypoperfusion in the visual
      cortex and in other regions alternatively might reflect direct central nervous
      system (CNS) involvement due to neuronal degeneration or to impaired vascular
      function caused by morphologically changed mitochondria in smooth muscle and
      endothelial cells. The data suggest CNS involvement in ophthalmoplegia plus with
      abnormalities of cerebral blood flow similar to those found in other
      mitochondrial encephalomyopathies.

PMID- 1999049
TI  - An evaluation of preoperative and postoperative ventilation and perfusion lung
      scintigraphy in the screening for pulmonary embolism after elective orthopedic
      surgery.
AB  - One hundred two patients undergoing elective knee or hip arthroplasty were
      studied with radionuclide ventilation scans (V) and perfusion scans (Q)
      preoperatively (preop) and postoperatively (postop) to assess their relative
      value in the diagnosis of asymptomatic pulmonary embolism (PE) after orthopedic
      surgery. Postop Q were read in combination with preop V and Q and postop V using
      prospective investigation of pulmonary embolism diagnosis (PIOPED) criteria. Of
      25 postop Q interpreted as either high or intermediate probability for PE, preop
      Q were judged useful in 96%; the postop V were useful in 78%; and the preop V
      were not helpful in any of the cases. Of 63 postop Q interpreted as low
      probability, preop Q were useful in 74%; the postop V were useful in only 33%;
      and the preop V were useful in only one case. When postop Q were read as normal
      (14 cases), none of the three auxiliary studies were found to be useful. Overall,
      postop V were more helpful than preop Q in only 2%, and preop V contributed
      significantly in only 1%. This experience suggests that preop Q alone is the most
      useful adjunct to the postop Q in the postoperative evaluation for PE. The
      authors conclude that to screen for asymptomatic PE after elective orthopedic
      surgery, preop Q should be performed in all cases, preop V are not necessary, and
      postop V need be performed only if a baseline preop Q is not available.

PMID- 1999051
TI  - Photopenic areas on bone scanning associated with childhood leukemia.
AB  - Photopenic areas on bone scintigraphy is a rare presentation of childhood
      leukemia. This includes the more common acute lymphocytic leukemia as well as the
      far less common myelomonocytic leukemia. Other causes of photopenia on bone
      scintigraphy in these patients include relapse with marrow replacement and
      associated bone necrosis. Methotrexate therapy has also previously been described
      as showing similar photopenic areas secondary to bone necrosis.

PMID- 1999052
TI  - Role of bone scanning in detection of subclinical bone metastasis in
      nasopharyngeal carcinoma.
AB  - One hundred thirty-two new patients with nasopharyngeal carcinoma and no evidence
      of distant metastases were evaluated for bone metastases with bone scanning.
      Forty-four patients had abnormal hypercaptation. These abnormal findings were
      considered related to benign diseases in 39 patients after correlating clinical
      examinations and skeletal radiographs. The remaining five patients had positive
      bone scanning which was suggestive of bone metastasis. There were 13 patients who
      developed symptomatic bone metastases over a follow-up period of 0.2-41 months.
      In three of these, the bone metastases corresponded to the sites of abnormal
      hypercaptation in the initial positive bone scanning. In view of the low
      sensitivity and specificity of bone scanning in this setting, routine bone
      scanning for staging nasopharyngeal carcinoma is not recommended. But in the
      research setting, baseline scanning is useful to make subsequent scanning more
      valuable, and it reduces false-positive results.

PMID- 1999053
TI  - Factors affecting bone mineral density in elderly men receiving chronic in-center
      hemodialysis.
AB  - Twenty-five elderly men receiving chronic hemodialysis had measurements of their
      bone mineral density (BMD) by dual-photon absorptiometry (DPA). Loss of BMD was
      much more pronounced in femoral necks than in lumbar vertebrae. Stepwise multiple
      liner-regression analysis showed that low BMD was associated with 1)
      hypoalbuminemia, hypermagnesemia, hyperaluminemia, and high serum alkaline
      phosphatase for femoral necks and 2) hypercalcemia and hypermagnesemia for lumbar
      vertebrae. These observations suggest that the femoral neck is the preferred site
      for measurement of BMD in dialysis patients. Along with factors directly
      affecting bone metabolism, nutritional factors may affect BMD in such patients.

PMID- 1999054
TI  - The role of Tc-99m IDA hepatobiliary and Tc-99m colloid hepatic imaging in
      primary biliary cirrhosis.
AB  - To assess the presence of primary biliary cirrhosis, 15 patients at various
      histopathologic stages were studied by Tc-99m IDA hepatobiliary and/or Tc-99m
      colloid hepatic imaging. In the earlier stages (I and II), seven of eight
      patients (88%) showed uniform hepatic retention of Tc-99m IDA. Of seven patients
      in the same stage, however, four (57%) showed no abnormality on Tc-99m colliod
      imaging. In three of these four negative patients (75%), uniform hepatic
      retention of Tc-99m IDA was noted. In the later stages (III and IV), all seven
      patients showed decreased clearance with or without delayed tracer appearance in
      the intestine and prominent hepatic retention on Tc-99m IDA imaging; with Tc-99m
      colloid imaging there was enlargement of the spleen and increased activity in the
      spleen and bone marrow. Thus, Tc-99m IDA imaging is considered to be more useful
      in revealing this functional disorder at the earlier stage of primary biliary
      cirrhosis and in evaluating progression from an earlier to a later stage of
      disease. Tc-99m colloid imaging also effectively evaluated progression.

PMID- 1999055
TI  - Physiologic assessment of coronary artery fistula.
AB  - Coronary artery fistula is an uncommon clinical entity. The most common coronary
      artery fistula is from the right coronary artery to the right side of the heart,
      and it is less frequent to the pulmonary artery. The effect of a coronary artery
      fistula may be physiologically significant because of the steal phenomenon
      resulting in coronary ischemia. Based on published reports, it is recommended
      that patients with congenital coronary artery fistulas be considered candidates
      for elective surgical correction to prevent complications including development
      of congestive heart failure, angina, subacute bacterial endocarditis, myocardial
      infarction, and coronary aneurysm formation with rupture or embolization. A
      patient is presented in whom treadmill-exercise thallium imaging was effective in
      determining the degree of coronary steal from a coronary artery fistula, leading
      to successful corrective surgery.

PMID- 1999056
TI  - Gallium scintigraphy in neoplastic angioendotheliosis of the lung.
AB  - A case of neoplastic angioendotheliosis of the lung is reported. A 56-year-old
      man presented with a 2-month history of fever, increased serum lactic
      dehydrogenase, and arterial hypoxemia. Chest radiography revealed diffuse
      reticulonodular opacity, whereas CT scanning showed diffuse small nodular areas
      of increased attenuation with indistinct borders. Diffuse pulmonary uptake of Ga
      67 was noted in scintigraphy. Combination chemotherapy designed for lymphoma
      induced a remission of the disease.

PMID- 1999057
TI  - Demonstration of medial meniscus tear by three-phase bone imaging.

PMID- 1999058
TI  - Spurious recurrence of pulmonary embolism after streptokinase therapy.

PMID- 1999059
TI  - Femoral and acetabular photopenia associated with septic hip arthritis.

PMID- 1999060
TI  - Incidental visualization of abdominal varices during cholescintigraphy.

PMID- 1999061
TI  - Polyostotic fibrous dysplasia as a mimic of bony metastatic disease.

PMID- 1999062
TI  - Lumbar puncture. Potential pitfall in In-111 labeled leukocyte scintigraphy.

PMID- 1999063
TI  - Periostitis due to low-dose fluoride intoxication demonstrated by bone scanning.

PMID- 1999064
TI  - Phantom kidney on renal scintigraphy.

PMID- 1999065
TI  - Pulmonary neoplasms simulating interlobar pleural effusions.
AB  - Loculated pleural effusions simulating neoplasms are a well known pitfall. The
      reverse is less well recognized. We describe three cases where tumours were
      initially diagnosed as loculated effusions. The differentiation of these two
      entities is discussed.

PMID- 1999067
TI  - Patient dose reduction in diagnostic radiology.

PMID- 1999066
TI  - Systemic air embolism: a complication of ventilator therapy in hyaline membrane
      disease.
AB  - Systemic air embolism in infants with hyaline membrane disease on positive
      pressure ventilation is a serious and frequently fatal complication. It is
      essential for both the paediatrician and radiologist to be aware of this disease
      entity. The incidence is increasing because of improved survival of very low
      birth weight infants and more aggressive therapy. We report two examples of
      systemic air embolism in infants.

PMID- 1999068
TI  - Mesenchymal hamartoma of the chest wall in infancy.
AB  - Two cases of mesenchymal hamartoma of the chest wall are presented. The clinical
      presentation, radiological and histological features of this rare tumour are
      discussed. The management, which may be conservative or surgical depends on the
      clinical symptoms, and this is also discussed.

PMID- 1999069
TI  - Comparison of liver histology with ultrasonography in assessing diffuse
      parenchymal liver disease.
AB  - To establish the accuracy of ultrasonography in assessing diffuse parenchymal
      liver disease we performed a prospective comparative study with histology in 50
      patients with a wide range of liver disease. Liver biopsy was performed within 24
      h of the ultrasound examination and ultrasonography was performed by a single
      operator who was unaware of clinical details of the patients. Histology was
      reviewed blind and the degree of steatosis graded mild, moderate or severe while
      increased portal fibrous tissue was graded mild, moderate or established
      cirrhosis. Thirty-six patients had steatosis and 31 patients had increased
      fibrous tissue on histology. Ultrasonography correctly identified steatosis in
      32/36 (89%) patients including all patients with the severe grade. Increased
      fibrous tissue was correctly identified in 24/31 (77%) with a sensitivity of 100%
      in patients with moderate fibrosis and established cirrhosis. Specificity was 93%
      for steatosis and 89% for increased fibrous tissue. These results show that
      ultrasonography can provide a non-invasive prediction of liver histology which in
      moderate and severe steatosis and advanced fibrosis can be both highly sensitive
      and specific.

PMID- 1999070
TI  - Renal sonography in long standing Lesch-Nyhan syndrome.
AB  - The Lesch-Nyhan syndrome is an x-linked defect of purine metabolism resulting in
      its classical form in major neurodevelopmental abnormality, hyperuricaemia, and
      hyperuricosuria. Uric acid calculi and crystalluria are common. Allopurinol is
      the main method of reducing serum and urinary uric acid levels, but results in
      xanthinuria and oxypurinoluria, both of which may cause crystal nephropathy and
      calculi. The variable ultrasonic appearances of multiple calculi and increased
      medullary echogenicity in four cases of long-standing treated disease and the
      nature of the renal disorder, which is at least partially iatrogenic, are
      described.

PMID- 1999071
TI  - Imaging after renal transplantation.

PMID- 1999072
TI  - Renal transplant vein stenosis: demonstration and percutaneous venoplasty of a
      new vascular complication in the transplant kidney.
AB  - Stenosis of the renal transplant vein has been demonstrated in eight patients
      undergoing investigation for renal dysfunction arising 3 weeks to 3 years after
      transplantation. The stenoses were diagnosed by duplex Doppler ultrasound in
      three cases and by angiography in the presence of arterio-venous fistula in five
      cases. In four patients percutaneous venous dilatation was performed with
      technical success in three. In two patients this was repeated for recurrent
      stenosis but sustained improvement in renal function was not observed.
      Progression of the venous stenoses was documented with one patient suffering
      graft loss due to complete venous occlusion.

PMID- 1999073
TI  - The distribution of recurrent varicose veins: a phlebographic study.
AB  - One hundred consecutive legs in 74 patients presenting with recurrent varicose
      veins were investigated by varicography. Forty recurrences occurred at the groin,
      80 in the thigh and 97 in the calf. Within each group different anatomical
      variations were encountered, and we describe the frequency of these and of
      certain commonly observed combinations. We also suggest possible causes, and
      discuss how the results of varicography may assist in surgical management.

PMID- 1999074
TI  - Ultrasound, computed tomography and magnetic resonance imaging in patellar
      tendinitis.
AB  - This prospective study describes the ultrasound, computerized tomography and
      magnetic resonance imaging findings in 16 cases of patellar tendinitis. In all
      cases tendon enlargement and reduced echogenicity were visible on ultrasound.
      Computerized tomography demonstrated enlargement of the tendon with reduced
      attenuation of the central portion. Magnetic resonance imaging showed focal
      tendon enlargement in all patients with high signal lesions in 88% of cases. This
      study has shown that patellar tendinitis may be identified with all three
      modalities. Ultrasound is recommended as the initial investigation in the
      assessment of patients with this condition.

PMID- 1999075
TI  - Pleural granulocytic sarcoma: CT characteristics.
AB  - The CT findings in a case of granulocytic sarcoma of the pleura are presented and
      correlated with pathology sections. CT features included diffuse, circumferential
      pleural thickening, multiple pleural fluid locules and mediastinal adenopathy.
      Similarities with the appearance of mesothelioma and metastatic pleural disease
      are discussed and the literature reviewed.

PMID- 1999076
TI  - Tuberculous broncho-oesophageal fistula in the acquired immunodeficiency
      syndrome.
AB  - Mycobacteria are the most common bacterial infections occurring in AIDS patients.
      Although the gastrointestinal tract is commonly involved, there has been only one
      case report of oesophageal infection. We report a patient in whom oesophageal
      tuberculosis was the presenting feature of AIDS and review the features of
      mycobacterial infections in AIDS. The incidence of extrapulmonary infection is
      common and mycobacterial oesophagitis should be considered in the differential
      diagnosis of oesophagitis in AIDS.

PMID- 1999077
TI  - Chondrosarcoma presenting as an anterior mediastinal mass.
AB  - We describe a chondrosarcoma presenting as an anterior mediastinal mass. The
      tumour was unusual in that it simulated more commonly occurring mediastinal
      tumours. There was relatively little destruction of the anterior chest wall and
      very little calcification within the lesion.

PMID- 1999078
TI  - Transalar sphenoidal encephalocele. Uncommon clinical and radiological findings.
AB  - A case of basal encephalocele protruding through a defect in the greater wing of
      the sphenoid bone is presented. The transalar type of encephalocele is uncommon
      and unclassified. This case, documented by computed tomography and magnetic
      resonance imaging, is unique in that it presented with trigeminal neuralgia and
      was associated with an angioma of the soft palate.

PMID- 1999079
TI  - Cerebral venous thrombosis.

PMID- 1999080
TI  - Intravascular contrast agents and renal failure.

PMID- 1999081
TI  - High-resolution computed tomography in extrinsic allergic alveolitis.
AB  - Seventeen patients with extrinsic allergic alveolitis were examined with high
      resolution computed tomography (CT). Increased attenuation of the lung parenchyma
      was present in eleven cases; the corresponding abnormality on chest radiography
      of ground-glass opacification was found in only five cases. The apparent upper
      zone sparing on chest radiography was not confirmed on CT which demonstrated a
      global increase in lung density. Several other abnormalities identified on CT in
      the subacute phase of extrinsic allergic alveolitis are described and correlated
      with chest radiographs. Whilst there is no single pathognomonic CT feature of
      extrinsic allergic alveolitis, there is a characteristic constellation of
      abnormalities which provide support for an otherwise uncertain clinical
      diagnosis.

PMID- 1999082
TI  - The consent process in the Thrombolysis in Myocardial Infarction (TIMI--phase I)
      trial.

PMID- 1999083
TI  - Ethics, statistics, and technology assessment: the use of a stopping rule and an
      independent policy and data monitoring board in a cohort study of perioperative
      cardiac morbidity. The Study of Perioperative Ischemia Research Group.

PMID- 1999084
TI  - Current options for the treatment of systemic scleroderma.
AB  - The epidemiology, pathology, diagnosis, and clinical manifestations of systemic
      scleroderma (SSc) are described, and therapeutic options are discussed. SSc is a
      rare condition of unknown etiology that occurs in a subset of scleroderma
      patients. It is distinguished by involvement of the small arteries, microvessels,
      and diffuse connective tissue. The degree of internal organ involvement is the
      main determinant of morbidity and mortality. Management of SSc may entail
      supportive, palliative, remittive, and immunosuppressive therapies. Supportive
      therapy involves maintaining the affected extremities at warm temperatures and
      the use of emollient creams. Results of palliative treatment are mixed. Toxic
      reactions may be associated with many of these medications. Dermatologic
      manifestations have been treated with nonsteroidal anti-inflammatory agents, low
      dose corticosteroids, dimethyl sulfoxide, and edetate disodium; peripheral and
      internal-organ vascular obstruction, with alpha-adrenergic blockers, angiotensin
      converting-enzyme inhibitors, and calcium-channel blockers. Antacids with alginic
      acid, histamine H2-receptor antagonists, sucralfate, and cholinergic-acting
      agents may be used to relieve GI symptoms. Lung infections should be treated
      promptly with antibiotics. No drug therapy has been successful in reducing the
      incidence of fatal cardiac arrhythmias or in preventing cardiac fibrosis.
      Captopril and enalapril are essential in the control of SSc renal crisis.
      Penicillamine may hold promise as a remittive therapy. The immunosuppressive
      agents fluorouracil, cyclosporine, and methotrexate, which have shown limited
      effectiveness in preliminary studies, merit further investigation. No therapeutic
      agent has yet been shown to alter the course of SSc on a consistent or long-term
      basis. Toxicity and drug interactions remain a major concern in patient
      management, and aggressive monitoring is essential.

PMID- 1999085
TI  - Use of angiotensin-converting-enzyme inhibitors in the management of renal
      disease.
AB  - The role of angiotensin-converting-enzyme inhibitors (ACEIs) in the treatment of
      progressive renal disease is described. Researchers have evaluated the use of
      ACEIs in patients with two types of progressive kidney disease: diabetic
      nephropathy and renal insufficiency associated with connective-tissue disease.
      When introduced early in the course of diabetic nephropathy, ACEIs appear to
      produce greater reductions in urinary protein concentrations than do other
      antihypertensive agents, even when systemic blood pressure does not decrease.
      They also slow the rate of decline of renal plasma flow and glomerular filtration
      rate. Results are less impressive when ACEIs are initiated at a later stage of
      disease. Captopril has been shown to be associated with a decline in serum
      creatinine level in patients with systemic scleroderma, and with reductions in
      blood pressure and increases in the glomerular filtration rate in patients with
      systemic lupus erythematosus. Because these patients were receiving other agents
      that might have influenced study outcome, specific conclusions about the efficacy
      of ACEIs in connective-tissue disease cannot yet be drawn. They may, however, be
      recommended as adjunctive agents in treatment of this condition. The relative
      safety of the ACEIs, combined with their ability to arrest or slow the
      progression of renal failure, makes them primary options in the management of
      selected renal diseases.

PMID- 1999086
TI  - Intravenous ciprofloxacin versus ceftazidime for treatment of nosocomial
      pneumonia and urinary tract infection.
AB  - Intravenous ciprofloxacin and ceftazidime were compared for efficacy in the
      treatment of nosocomial pneumonia and urinary tract infection (UTI). Patients
      with nosocomial pneumonia were randomized to receive ciprofloxacin (as the
      lactate salt) 300 mg i.v. every 12 hours or ceftazidime (with sodium carbonate) 2
      g i.v. every eight hours. Patients with UTI were randomized to receive
      ciprofloxacin 200 mg i.v. every 12 hours or ceftazidime 1 g i.v. every eight
      hours. Sputum and urine specimens were collected before, during, and after
      therapy. For patients with pneumonia, the organisms most frequently isolated
      before treatment began were Escherichia coli, Haemophilus influenzae, Klebsiella
      pneumoniae, and Proteus mirabilis. Of the 17 pneumonia patients who completed
      ciprofloxacin treatment, 15 (88%) had resolution of signs and symptoms or
      improvement. Of the 15 ceftazidime-treated pneumonia patients, 13 (87%) had
      resolution or improvement. Staphylococcus aureus, Streptococcus species,
      Acinetobacter species, and K. pneumoniae infections persisted for the
      ciprofloxacin treatment failures. Infections by Enterobacter cloacae and
      Acinetobacter species persisted for the ceftazidime treatment failures. For UTI
      patients, E. coli was the organism most frequently isolated before treatment. All
      14 UTI patients who completed treatment showed resolution or improvement. In the
      ciprofloxacin group two patients were superinfected by Enterococcus species, and
      in the ceftazidime group there were two superinfections by Enterococcus species
      and one by Enterobacter cloacae. Intravenous ciprofloxacin was as effective as
      ceftazidime in the treatment of nosocomial pneumonia and urinary tract infection.
      Caution should be exercised when treating serious infections by streptococci or
      staphylococci.

PMID- 1999087
TI  - Pancreatitis during pentamidine therapy in patients with AIDS.

PMID- 1999088
TI  - Blood conservation--a critical care imperative.

PMID- 1999089
TI  - Hypothermia after cardiac arrest.

PMID- 1999090
TI  - Plugging the leaks? New insights into synthetic colloids.

PMID- 1999091
TI  - Hemodynamic benefit of maintaining atrioventricular synchrony during cardiac
      pacing in critically ill patients.
AB  - OBJECTIVE: To determine the hemodynamic effects of maintaining atrioventricular
      synchrony during emergency cardiac pacing in critically ill patients. DESIGN:
      Prospective, within patient double-blind study. SETTING: ICU or coronary care
      unit patients in a university hospital. PATIENTS: Forty (23 cardiac surgery, ten
      acute myocardial infarction, and seven general intensive care) seriously ill
      patients with severe symptomatic bradycardia. INTERVENTION: Initial randomization
      of patients to receive either a pacing mode where atrioventricular
      synchronization was maintained (atrioventricular pacing: atrial demand,
      atrioventricular sequential, atrioventricular universal) or a mode of pacing
      where atrioventricular synchrony was not preserved (ventricular demand pacing).
      MEASUREMENTS AND MAIN RESULTS: The cardiac output increased from a mean of 4.5 +/
      1.7 L/min (95% confidence intervals: 4.0 to 5.0 L/min) during ventricular demand
      pacing to 5.3 +/- 1.7 L/min (95% confidence intervals: 4.9 to 5.9 L/min) during
      atrioventricular pacing (p less than .0001) despite trivial decreases in CVP from
      14 +/- 4 mm Hg (95% confidence intervals: 13 to 15 mm Hg) to 13 +/- 5 mm Hg (95%
      confidence intervals: 12 to 15 mm Hg) and pulmonary artery occlusion pressure
      from 18 +/- 5 mm Hg (95% confidence intervals: 16 to 20 mm Hg) to 17 +/- 5 mm Hg
      (95% confidence intervals: 15 to 18 mm Hg). At the same time, mean arterial
      pressure (MAP) increased from 74 +/- 15 mm Hg (95% confidence intervals: 64 to 79
      mm Hg) to 83 +/- 15 mm Hg (95% confidence intervals: 80 to 88 mm Hg) and left
      ventricular stroke work index from 22 +/- 10 g.m/m2 (95% confidence intervals: 19
      to 25 g.m/m2) to 30 +/- 11 g.m/m2 (95% confidence intervals: 26 to 33 g.m/m2).
      There was no significant change in mean pulmonary artery pressure, pulmonary
      vascular resistance index, or systemic vascular resistance index. CONCLUSION:
      When cardiac pacing is required in critically ill patients, maintaining
      atrioventricular synchrony increases stroke volume, cardiac output, and MAP
      apparently with minimal effects on preload and afterload.

PMID- 1999092
TI  - Adequate resuscitation of burn patients may not be measured by urine output and
      vital signs.
AB  - OBJECTIVE: To compare vital sign and urine output monitoring of seriously burned
      patients with invasive monitoring during early resuscitation. DESIGN:
      Retrospective review. SETTING: A university hospital burn unit. PATIENTS:
      Fourteen seriously burned patients who had pulmonary arterial monitoring.
      Monitoring data were compared at baseline and after fluid challenges. RESULTS:
      There was no correlation between invasively derived physiologic variables and
      vital signs and urine output. Vital signs and urine output changed little after
      fluid challenge, while variables from invasive monitoring demonstrated
      significant change. In half of the patients, oxygen consumption increased after
      fluid challenge; vital signs and urine output did not distinguish these patients.
      CONCLUSIONS: The use of urinary output and vital signs to guide initial burn
      resuscitation may lead to suboptimal resuscitation. Invasive cardiorespiratory
      monitoring may be necessary to optimize resuscitation of seriously burned
      patients.

PMID- 1999093
TI  - Pulmonary aspiration during emergency endoscopy in patients with upper
      gastrointestinal hemorrhage.
AB  - OBJECTIVE: To evaluate the frequency and significance of aspiration and its
      clinical importance in patients with upper GI bleeding undergoing
      esophagogastroduodenoscopy in the ICU. DESIGN: Thirty consecutive patients with
      active and severe upper GI bleeding were studied. SETTING: ICU. PATIENTS: Ranged
      in age from 20 to 78 yr with an equal number of males and females. INTERVENTIONS:
      All patients had continuous pulse oximetry monitoring and had chest radiographs
      obtained less than 12 hr before endoscopy and less than 4 hr after endoscopy.
      MEASUREMENTS: Six (20%) of 30 patients developed new lung infiltrates after
      esophagogastroduodenoscopy. In this group of patients, preendoscopy chest
      radiographs were obtained after less than 4 hr. In five of these patients,
      infiltrates were accompanied by fever and/or leukocytosis and oxygen desaturation
      to less than 90% during the esophagogastroduodenoscopy. CONCLUSION: Clinically
      significant aspiration pneumonia frequently complicates
      esophagogastroduodenoscopy in upper GI bleeding patients and is an important
      mechanism of esophagogastroduodenoscopy-induced hypoxia.

PMID- 1999094
TI  - Outcome following prolonged intensive care unit stay in multiple trauma patients.
AB  - OBJECTIVE: To describe the hospital course and outcomes of trauma patients
      requiring ICU stays greater than 30 days and the charges they incur. DESIGN: A
      retrospective case series analysis of data collected from patient charts and
      trauma registry. SETTING: A Level I regional trauma center that is part of a
      statewide trauma system. PATIENTS: Over a 3-yr period, 87 patients (3% of all
      trauma ICU admissions) had prolonged stays (greater than 30 days) in the ICU;
      they constitute the study group. Blunt trauma was responsible for 90% of
      injuries, and the mean Injury Severity Score was 34 +/- 16 SD. RESULTS:
      Mechanical ventilation was required for 78.5% of the time spent in the ICU. The
      mean time spent on mechanical ventilators was 47 +/- 23 days; in the ICU, 60 +/-
      27 days; and in the hospital, 72 +/- 29 days. Infectious complications occurred
      in 90% and organ dysfunction was seen in 76% of patients. The overall mortality
      rate was 17.2% (31% for patients greater than 65 yr). Patients less than 40 yr
      had lower mortality rates despite a significantly higher Injury Severity Score
      and lower Glasgow Coma Scale score compared with those greater than 65 yr. More
      patients greater than 65 yr were discharged to chronic care facilities than those
      younger (23% vs. 5%). The number of patients followed at 3 and 12 months after
      discharge was 74% and 54%, respectively, with only two deaths. The mean hospital
      and professional charges to the patients were $101,000 +/- 61,000 and $35,000 +/-
      13,000, respectively. CONCLUSION: Length of ICU stay was most closely associated
      with the need for mechanical ventilation. The presence of premorbid illness, age
      greater than 65 yr, and organ dysfunction was associated with increased
      mortality. Although trauma patients requiring prolonged ICU stays utilize many
      resources, the ultimate outcome may be fairly good.

PMID- 1999095
TI  - Hemodialysis for acute renal failure in patients with hematologic malignancies.
AB  - OBJECTIVE: To assess the prognosis of patients with hematologic malignancies in
      acute renal failure who require hemodialysis. DESIGN: Retrospective study.
      SETTING: ICU. PATIENTS: Forty-three consecutive patients. METHODS: Prognostic
      analysis using both univariate and multivariate (stepwise regression) methods.
      RESULTS: Fifteen (35%) patients recovered from acute renal failure and 12 (28%)
      were discharged from the ICU. The prognosis of patients with acute renal failure
      linked to sepsis is poorer than the prognosis of the patients with acute renal
      failure from other etiologies. Only one patient survived in the former group (n =
      26) and 11 in the latter group (n = 17); p less than .0001 in multivariate
      analysis. When accompanied by associated respiratory failure, mortality rate was
      higher (93% vs. 33%; p less than .0001). The Simplified Acute Physiology Score
      (SAPS) calculated within the first 24 hr of admission was significantly (p less
      than .001) related to mortality when the SAPS was greater than or equal to 13.
      The presence of neutropenia and the type of hematologic malignancy were not
      related to a worse prognosis. Tolerance to hemodialysis appeared good, and
      complications were rare.

PMID- 1999096
TI  - Predictors of postextubation stridor in pediatric trauma patients.
AB  - OBJECTIVE: To determine which factors are the best predictors of postextubation
      stridor in pediatric trauma patients. DESIGN: Prospective cohort study. SETTING:
      The Burn and Trauma ICUs at Harborview Medical Center from March to September
      1989. PATIENTS: Children were eligible for the study if they were less than 15 yr
      old, were intubated for greater than 12 hr, and did not have underlying
      cardiopulmonary disease. The study included 25 patients with 30 extubations. RISK
      FACTORS ASSESSED: Age, type of injury (burn vs. trauma), location of intubation
      ("field" vs. hospital), endotracheal tube size, length of intubation, and
      presence of an airleak around the tube at the time of extubation at 30 cm H2O
      pressure. MAIN OUTCOME MEASURE: Moderate to severe postextubation stridor
      requiring treatment with racemic epinephrine, helium-oxygen, reintubation, or
      tracheostomy. RESULTS: Treatment for postextubation stridor was required after 11
      (37%) of 30 extubations, with five reintubations and one tracheostomy. The best
      predictor of postextubation stridor was absence of an airleak at the time of
      extubation (sensitivity 100%, positive predictive value 79%, p less than .001),
      followed by type of injury (facial burn vs. all others; sensitivity 64%, positive
      predictive value 88%, p less than .001). After controlling for these two factors,
      no other factor studied was a significant predictor of postextubation stridor.
      CONCLUSION: In pediatric trauma patients, mechanism of injury (facial burn vs.
      other) and absence of an airleak at the time of extubation are the strongest
      factors predicting postextubation stridor. Patients with one or both risk factors
      require special attention to airway management.

PMID- 1999098
TI  - Pulmonary effects of ischemic limb reperfusion: evidence for a role for oxygen
      derived radicals.
AB  - OBJECTIVE: To evaluate the lung as a reperfusion target after limb ischemia
      reperfusion, and to measure specifically the oxygen radical response to this
      reperfusion. DESIGN: Paired simple randomized, with continuous interval data in
      dependent variable and both continuous and nominal independent variables.
      SUBJECTS AND INTERVENTION: Sprague-Dawley male rats (n = 195) were anesthetized
      and both hind limbs occluded for 3.75 hr, the overnight LD50. Alveolar lavage was
      performed on the animals 1 hr after reperfusion or on survivors 20 hr after
      reperfusion. Groups were either undosed or pretreated with alpha-tocopherol as an
      antioxidant (50 mg/kg.day) 2 days before ischemia. MEASUREMENTS AND MAIN RESULTS:
      Luminol-enhanced chemiluminescence was measured in both phorbol myristate acetate
      stimulated and unstimulated macrophages. Nanomoles of superoxide radicals per
      10(6) alveolar cells/min were also measured using a cytochrome c reduction assay.
      A significant (p less than .01, Student's t-test), time-dependent increase in
      response of cells from ischemic-reperfused rats was seen. Pretreatment with
      antioxidant had no effect at 1 hr, but significant differences were seen in the
      20-hr survivors. CONCLUSIONS: These studies show that alveolar lavage cells, 95%
      macrophages, reflect the reperfusion of ischemic-reperfused hind limbs by a
      significant increase in oxygen radical activity, an effect partly suppressed in
      antioxidant-dosed survivors.

PMID- 1999097
TI  - Helium-oxygen mixture in the treatment of postextubation stridor in pediatric
      trauma patients.
AB  - OBJECTIVE: To assess the effectiveness of a helium-oxygen mixture in reducing
      post-extubation stridor in children hospitalized for burns or trauma. DESIGN:
      Randomized, controlled crossover trial. SETTING: Harborview Medical Center's Burn
      and Trauma ICUs from March to September 1989. PATIENTS: Children less than 15 yr
      old who were electively extubated and had symptoms of postextubation stridor, but
      required less than or equal to 35% oxygen. INTERVENTION: Each treatment (helium
      oxygen and oxygen-supplemented room air) was given in random order for 15 min
      after extubation. MEASUREMENTS: Respiratory distress was assessed by a physician
      blinded to treatment order using a standard stridor score and clinical judgment.
      RESULTS: There were 13 children with 15 extubations; seven (47%) of 15 patients
      required subsequent treatment with racemic epinephrine or reintubation. Stridor
      scores were lower with helium-oxygen than with oxygen-supplemented room air (2.8
      vs. 3.7, p less than .005), and helium-oxygen was preferred in eight of nine
      trials in which one treatment was clearly favored by the physician. CONCLUSION:
      Because helium-oxygen therapy can reduce stridor scores and is clinically
      preferred by physicians caring for stridorous children, it may be a useful
      adjunctive therapy in pediatric trauma patients with postextubation stridor.

PMID- 1999099
TI  - Airway pressure release ventilation in a neonatal lamb model of acute lung
      injury.
AB  - OBJECTIVE: To determine if airway pressure release ventilation (APRV) is feasible
      in a neonatal animal model with acute lung injury. DESIGN: Nonrandomized,
      repeated, bracketed measures. SETTING: University research laboratory. SUBJECTS:
      Seven neonatal sheep (5.6 +/- 0.6 kg), less than 10 days of age. INTERVENTIONS:
      Acute lung injury was induced by oleic acid infusion and cardiorespiratory
      profiles were compared during spontaneous ventilation at ambient airway pressure,
      continuous positive airway pressure (CPAP), APRV, and conventional positive
      pressure ventilation (PPV). MEASUREMENTS AND RESULTS: Oleic acid resulted in
      acute lung injury with stable cardiorespiratory status during the 3-hr study
      period. Mean airway pressure (Paw) was comparable for all three positive-pressure
      modes (CPAP 13.4 +/- 1.5, APRV 13.5 +/- 1.4, PPV 13.9 +/- 1.4 cm H2O, NS). After
      acute lung injury, CPAP increased arterial oxygenation compared with spontaneous
      ventilation (77.3 +/- 6.9 vs. 57.7 +/- 4.2 torr [10.3 +/- 0.9 vs. 7.7 +/- 0.6
      kPa], p less than .05), and this increase was maintained during APRV (73.3 +/-
      5.6 vs. 77.3 +/- 6.9 torr [9.8 +/- 0.7 vs. 10.3 +/- 0.9 kPa], NS). Alveolar
      ventilation was increased by APRV compared with CPAP (PaCO2 29 +/- 1 vs. 41 +/- 2
      torr [3.9 +/- 0.1 vs. 5.4 +/- 0.3 kPa], p less than .05) without impairment of
      cardiovascular performance (cardiac output 1.18 +/- 0.16 vs. 1.20 +/- 0.17 L/min,
      NS). To achieve ventilation equivalent to APRV during PPV, peak Paw was greater
      (36.4 +/- 3.2 vs. 19.7 +/- 1.7 cm H2O, p less than .05) and cardiac output (0.94
      +/- 0.11 vs. 1.18 +/- 0.16 L/min, p less than .05) and mean arterial pressure (91
      +/- 7 vs. 96 +/- 6 mm Hg, p less than .05) were decreased during PPV compared
      with APRV. CONCLUSIONS: In this neonatal laboratory model of acute lung injury,
      APRV maintained oxygenation and augmented alveolar ventilation compared with
      CPAP. Compared with PPV, APRV provided similar ventilation and oxygenation, but
      at lower peak Paw than PPV, without compromising cardiovascular performance.

PMID- 1999101
TI  - Age effects susceptibility to pulmonary barotrauma in rabbits.
AB  - OBJECTIVE: We studied the effect of age on the development of pulmonary
      barotrauma after mechanical ventilation with high peak inspiratory pressures
      (PIP). DESIGN: Young (4 to 6 wk old) and adult rabbits were ventilated for 1 hr
      at PIPs of 15, 30, and either 45 cm H2O (young group) or 55 cm H2O (adult group).
      MEASUREMENTS AND MAIN RESULTS: The pulmonary capillary filtration coefficient
      (Kf,c) was measured in an isolated lung perfusion system after the animals were
      killed. In young rabbits, Kf,c increased significantly from the 15 cm H2O PIP
      value in both the 30 cm H2O (55%) and 45 cm H2O (507%) PIP groups, whereas Kf,c
      was increased in adult rabbits only in the 55 cm H2O (113%) PIP group. Kf,c was
      significantly (p less than .01) higher in young rabbits than in adult rabbits
      after ventilation, with every level of PIP being 91% higher at 15 cm H2O PIP and
      440% higher at 45 to 55 cm H2O PIP. Also, a greater incidence of pneumothorax and
      airleaks was observed in the young rabbits. Pressure-volume loops demonstrated
      that the young rabbits had more compliant lungs and chest wall than adult
      rabbits. CONCLUSIONS: These data indicate that the lungs of young rabbits had a
      higher baseline microvascular permeability and were more susceptible to the
      development of ventilator-induced increased microvascular permeability. More
      compliant lungs and chest wall and the larger distending volumes attained at each
      peak airway pressure appear to be the mechanisms.

PMID- 1999100
TI  - Mild hypothermic cardiopulmonary resuscitation improves outcome after prolonged
      cardiac arrest in dogs.
AB  - BACKGROUND AND METHODS: This study was designed to explore the effect of mild
      cerebral and systemic hypothermia (34 degrees C) on outcome after prolonged
      cardiac arrest in dogs. After ventricular fibrillation with no flow of 10 min,
      and standard external CPR with epinephrine (low flow) from ventricular
      fibrillation time of 10 to 15 min, defibrillation and restoration of spontaneous
      normotension were between ventricular fibrillation time of 16 and 20 min. This
      procedure was followed by controlled ventilation to 20 hr postarrest and
      intensive care to 72 hr postarrest. In control group 1 (n = 10), core temperature
      was 37.5 degrees C; in control group 2 (n = 10), cooling was started immediately
      after restoration of spontaneous normotension; and in group 3 (n = 10), cooling
      was initiated with start of CPR. Cooling was by clinically feasible methods.
      RESULTS: Best overall performance categories achieved (1 = normal; 5 = brain
      death) were better in group 2 (p = .012) and group 3 (p = .005) than in group 1.
      Best neurologic deficit scores were 36 +/- 14% in group 1, 22 +/- 15% in group 2
      (p = .02), and 19 +/- 18% in group 3 (p = .01). Brain histopathologic damage
      scores were also lower (better) in groups 2 (p = .05) and 3 (p = .03). Myocardial
      damage was the same in all three groups. CONCLUSION: Mild cerebral hypothermia
      started during or immediately after external CPR improves neurologic recovery.

PMID- 1999102
TI  - Acute airway injury during high-frequency jet ventilation and high-frequency
      oscillatory ventilation.
AB  - BACKGROUND AND METHODS: We compared tracheal histologic injury patterns, airway
      pressure (Paw) requirements, and in vivo and in vitro estimate of airway
      humidification in 13 adult cats with normal lungs mechanically ventilated for 16
      hr. Six animals were treated with high-frequency jet ventilation at 400
      breaths/min and seven animals with high-frequency oscillatory ventilation at 900
      breaths/min. RESULTS: Peak airway pressure, Paw, mean Paw, and end-expiratory
      pressure requirements were significantly higher for high-frequency oscillatory
      ventilation as compared with high-frequency jet ventilation for similar gas
      exchange (p less than .01). While in vivo estimates of airway humidification
      suggested progressively greater H2O delivery into the respirator circuit, and
      therefore the airway, with higher frequencies, the in vitro study suggested
      similar relative humidities of the delivered gases during both types of
      mechanical ventilation. Tracheal injury, measured using a semiquantitative
      scoring system, was scored similarly for both ventilators studied despite the
      higher pressure requirements seen with the high-frequency oscillator.
      CONCLUSIONS: In this animal model, high-frequency ventilation using either jet or
      oscillation techniques produced similar inflammatory tracheal damage despite
      differences in Paw exposure and humidity.

PMID- 1999103
TI  - Pulmonary artery occlusion-left atrial pressure gradient: an important factor in
      determining pulmonary venous vascular resistance in acute pulmonary failure.
AB  - OBJECTIVE: To determine whether pulmonary artery occlusion pressure (PAOP)
      accurately reflects left atrial pressure (LAP) in acute pulmonary failure.
      DESIGN: Sham-controlled laboratory investigation on Goettingen minipigs.
      INTERVENTIONS: Induction of acute respiratory failure by a 4-hr infusion of live
      Escherichia coli bacteria in 11 animals; two animals served as the control group.
      Anesthesia was obtained with methohexital/piritramide and pancuronium bromide.
      MEASUREMENTS AND MAIN RESULTS: Cardiac output and pressures were measured by
      means of femoral artery, pulmonary artery, and left atrial catheters. Arterial
      alveolar Po2 ratio was calculated to evaluate pulmonary function. Measurements
      were obtained before and after 1 and 2 hr of the E. coli infusion. Statistical
      significance was tested with analysis of variance. E. coli infusion caused the
      hypodynamic shock and respiratory failure. The PAOP-LAP gradient was -0.3 +/- 1.6
      mm Hg before bacteremia and increased significantly (p less than .001) to 2.9 +/-
      1.8 and 3.4 +/- 2.0 mm Hg after 1 and 2 hr of bacteremia, respectively. No
      significant changes occurred in the sham group. CONCLUSIONS: A PAOP-LAP gradient
      may develop during acute respiratory failure. Therefore, pulmonary venous
      vascular resistance may be underestimated if its determination is based on PAOP.
      An increase in bronchial to pulmonary blood flow and pulmonary venoconstriction
      are discussed as hypothetical causes of a PAOP-LAP gradient during acute
      respiratory failure.

PMID- 1999104
TI  - Stable and reproducible porcine model of acute lung injury induced by oleic acid.
AB  - BACKGROUND AND METHODS: Previous studies on acute lung injury induced with oleic
      acid did not attempt to limit the influence of secondary changes on pulmonary
      circulation, and cardiopulmonary variable data were only collected and processed
      intermittently. Our study was designed to continuously monitor the following
      variables in five swine: systemic and pulmonary pressure; mixed venous oxygen
      saturation (SVO2) and arterial oxygen saturation (SaO2); minute oxygen
      consumption and CO2 production before, during, and for 4 hr after the infusion of
      oleic acid. A personal computer was programmed to produce 20-sec updates of
      deadspace ratio (VD/VT), venous admixture (Qsp/Qt), pulmonary (PVR) and systemic
      vascular resistance (SVR), and cardiac output (Qt) from these data. RESULTS:
      During the oleic acid infusion, there were increases in PVR, SVR, heart rate
      (HR), mean pulmonary arterial pressure (MPAP), Qsp/Qt, and VD/VT, and a decrease
      in Qt, SaO2, and SVO2. Thirty minutes after the oleic acid infusion, there was a
      further increase in HR, Qsp/Qt, and VD/VT, while MPAP, PVR, and SVR gradually
      decreased to pre-oleic acid infusion levels. No further decrease in SaO2, SVO2,
      and Qt was observed during that time. After the 30-min period, there was no
      further change in the cardiopulmonary variables. CONCLUSION: Our method of
      continuous monitoring was able to demonstrate in swine both the dynamic changes
      during, and stability after, the oleic acid infusion.

PMID- 1999105
TI  - Placement considerations for measuring thermodilution right ventricular ejection
      fractions.
AB  - BACKGROUND AND METHODS: Clinical examination of right ventricular (RV)
      performance has been hampered by the inability to measure easily RV volumes and
      ejection fraction. This study was performed to examine the effects of catheter
      position on thermodilution RVEF measurements. Six pigs (80 to 100 kg) were
      instrumented with an RV thermodilution catheter in the pulmonary artery, an
      injectate catheter in the right atrium, an atrial pacing electrode, and a
      systemic arterial catheter. RVEF measurements were determined using
      thermodilution in two ways: a) with incremental increases in pulmonary valve to
      thermistor distance; and b) with incremental increases in injectate port to
      tricuspid valve distance. These measurements were obtained at a paced rate of 102
      +/- 2 beats/min and then repeated with pacing-induced tachycardia (140
      beats/min). RESULTS: There was no significant difference in thermodilution RVEF
      measurements with the thermistor positioned 0 to 10 cm from the pulmonary valve
      at either heart rate. A significant reduction in RVEF occurred with the injection
      port located 5 to 7 cm proximal to the tricuspid valve, with this decrease
      becoming more pronounced during tachycardia. CONCLUSIONS: These results
      demonstrate that RVEF measurements can be reliably obtained using thermodilution.
      In these large hearts, thermodilution RVEF measurements appear to be independent
      of thermistor position within the pulmonary artery. However, large distances from
      injectate port to tricuspid valve reduced RVEF measurements.

PMID- 1999106
TI  - New method for monitoring pulmonary artery catheter location.
AB  - OBJECTIVE: To test the ability of a modified pulmonary artery (PA) monitoring
      catheter to detect distal catheter migration. DESIGN: Prospective nonrandomized
      trial. PATIENTS: Surgical ICU patients requiring invasive hemodynamic monitoring.
      INTERVENTIONS: Eight patients received PA catheters modified to include a right
      ventricular (RV) pressure monitoring port located 7 cm from the tip. Fifteen
      patients received catheters with an RV port located 10 cm from the tip. Guided by
      the RV port pressure waveform, catheters were initially positioned so that the RV
      port was located just proximal to the pulmonic valve. MEASUREMENTS AND MAIN
      RESULTS: Pulmonary capillary occlusion pressure (PAOP) could not be obtained in
      six of the eight patients receiving the 7-cm RV port catheter unless the RV port
      was advanced into the PA. PAOP was consistently obtained in all 15 patients
      receiving the 10-cm RV port catheter, with the RV port positioned in the RV.
      Chest radiographs confirmed a central PA catheter position. In this group, distal
      migration of the catheter occurred 14 times in eight patients, as detected by
      appearance of a PA pressure waveform at the RV port. Distal migration was
      corrected by withdrawal of the catheter until an RV waveform reappeared at the RV
      port. CONCLUSIONS: We conclude that distal catheter migration occurs frequently
      with PA monitoring catheters, but can be detected at the bedside with a catheter
      modified to include an RV port 10 cm from the tip. This new catheter may add a
      margin of safety to PA monitoring and lower its overall cost by eliminating the
      need for chest radiographs ordered solely to confirm catheter tip location.

PMID- 1999107
TI  - Endotracheal intubation as a risk factor for complications of nasoenteric tube
      insertion.

PMID- 1999108
TI  - Prognostic value of C-reactive protein level in severe infectious purpura: a
      comparison with eight other scores.

PMID- 1999109
TI  - Intensive care order writing practices in the USA: results of a nationwide study.

PMID- 1999110
TI  - Severe cardiac, respiratory, and metabolic complications of massive verapamil
      overdose.

PMID- 1999111
TI  - Complication of central venous catheter insertion: fragmentation of a guidewire
      with pulmonary artery embolism.

PMID- 1999112
TI  - Neonatal vein of Galen aneurysms: severe coagulopathy associated with
      transtorcular embolization.

PMID- 1999113
TI  - Appendicitis masquerading as acute porphyria.

PMID- 1999114
TI  - Stress ulcers in the neurosurgical critical care patient.

PMID- 1999115
TI  - Automatic injectors--needle length.

PMID- 1999116
TI  - Detoxification of septic plasma by adsorption: clinical application.

PMID- 1999117
TI  - Informed consent.

PMID- 1999118
TI  - Effects of topical antimicrobial agents on the human neutrophil respiratory
      burst.

PMID- 1999119
TI  - Fluid resuscitation and colloid-crystalloid controversy: new thoughts on an old
      debate.

PMID- 1999120
TI  - Cytophotometric analysis of corresponding cytological and histological cervical
      intraepithelial neoplasia grade III specimens.
AB  - Cytophotometric analysis of cervical intraepithelial neoplasia grade III (CIN
      III) was performed in 22 cytological smears (CS) and in 22 corresponding cytospin
      specimens retrieved from selected areas of paraffin-embedded tissues (PEC). The
      average time interval between cytological and histological diagnosis was 6 weeks.
      CIN III nuclei in CS and PEC specimen were Thionin-Feulgen stained and digitized.
      Beside the visual classification of DNA ploidy patterns, the 2.5c and 5c
      exceeding rates and the specimen mean and standard deviation values of 21
      photometric features were also analyzed. It was shown that, although there was a
      significant correlation between DNA ploidy patterns in corresponding PEC and CS
      specimen, the DNA patterns were dissimilar in eight of 22 cases. The DNA index,
      as represented by 2.5c and 5c exceeding rates, was significantly higher in the CS
      specimen. High-resolution cytophotometric analysis of cell nuclei in CS and PEC
      specimens showed significant differences for a large number of nuclear
      photometric features. These findings can possibly be explained by differences in
      selection of CIN III cells from CS and PEC specimens and by differences between
      fixation procedures as used for the two techniques. It was concluded that
      cytophotometric data of CS and PEC specimens representing CIN III lesions should
      not be regarded as interchangeable.

PMID- 1999121
TI  - Nuclear texture parameters as discriminant factors in cell cycle and drug
      sensitivity studies.
AB  - The authors have recently shown that cell cycle characteristics of in situ cell
      populations can be determined using the SAMBA 200 cell image processor by
      computing 15 densitometric and texture parameters on each Feulgen-stained nucleus
      and multiparametric analysis of data. The present paper displays the importance
      of chromatin pattern assessment and detection of conformational changes in DNA
      structure, based on nine nuclear texture parameters measured from the grey level
      cooccurrence and the run-length section matrices. Reference files were
      constructed by merging respective reference files (G0/G1, S, G2 and M) of MDA AG
      and MCF-7, two mammary epithelial cell lines presenting different morphological
      aspects and hormone responses, these files were found to be valid in the
      reclassification of any mammary epithelial cell in culture with a diploid or near
      diploid pattern. Moreover, the authors demonstrate that chromatin texture
      changes, following direct interaction of chemotherapeutic drugs with DNA, may be
      assessed owing to nuclear texture parameters. Consecutive to daunomycin addition
      (0.5 microgram/ml) and concomitant to the appearance of nuclear morphological
      alterations in MDA AG sensitive cells as viewed by microscopic observation,
      discriminant factorial analysis showed progressively increasing erroneous
      reclassification from 15 to 72 h of treatment. These experimental results were
      exploited with a kinetic mathematical model to quantify the daunomycin blocking
      effect: 20% in S phase and 80% in G2 phase. Interestingly, no textural change was
      observed on MDA A1 anthracycline resistant cells, indicating that these texture
      parameters may permit distinction of drug sensitive cells. This methodology 1)
      can be applied to test in vitro resistance-reversal molecules, 2) may be extended
      to other therapeutic agents giving rise to conformational changes in DNA
      structure, and 3) can be applied to cytopunctions or imprints of tumor biopsies
      with diploid-like DNA content to follow evolution of drug sensitivity or
      resistance during course of therapy.

PMID- 1999122
TI  - Modalities of synthesis of Ki67 antigen during the stimulation of lymphocytes.
AB  - The antibody Ki67 is currently used to evaluate the proliferative fraction of
      solid tumors and some hematological malignancies. We have used phytohemagglutinin
      (PHA)-stimulated peripheral blood lymphocytes as a model to study the entry of
      quiescent cells into cell cycle and to follow their progress to the next cycle.
      Flow cytometric analysis of lymphocyte samples stained with the antibody Ki67 and
      a DNA marker has allowed us to follow the expression of Ki67 antigen (Ki67 Ag) as
      a function of the position of the cells in the cell cycle. The use of drugs
      blocking the stimulated lymphocytes in different phases of the cell cycle
      permitted us to demonstrate that Ki67 Ag expression started from the beginning of
      the first S phase. The level of Ki67 Ag increased during S phase until mitosis,
      when its expression was maximal. After division, the cells in G1 phase showed a
      decrease in Ki67 Ag expression (possibly corresponding to degradation) until they
      reentered S phase, when the level of Ki67 Ag increased again. The results confirm
      that the expression of Ki67 Ag is related to the proliferative state of the cells
      and suggest that it may be used to determine the proliferative cell fraction in
      hematopoietic tissues.

PMID- 1999123
TI  - Aberrant Ki-67 expression in normal bone marrow revealed by multiparameter flow
      cytometric analysis.
AB  - Ki-67 is a commercially available monoclonal antibody that reacts with a nuclear
      antigen detectable in proliferating cells only. Since its first description, it
      has been widely used as a "universal" proliferation marker and few groups have
      questioned the validity of the initially described reactivity, although this was
      tested only on very restricted experimental models. We wanted to check its
      reactivity on normal bone marrow (BM) samples using a multiparameter flow
      cytometric analysis. Although we were able to reproduce the findings of Ki-67
      positivity on cultured and stimulated cells, we could not detect any convincing
      Ki-67 positivity on nuclei of normal BM samples. These samples all had a
      noticeable proliferating compartment as evidenced by their DNA content. These
      data are in contrast with the data we obtained starting from stressed marrows and
      marrows cultured in the presence of hematopoietic growth factors, where we found
      a marked Ki-67 positivity. This discrepancy suggests that bone marrow cells,
      growing and proliferating under steady-state conditions and guided by natural
      control mechanisms, may lose their Ki-67 expression upon exiting the progenitor
      compartment and entering the differentiating compartment.

PMID- 1999124
TI  - Introduction of antibody into viable cells using electroporation.
AB  - Conditions for labelling an intracellular antigen, p21ras, using electroporation
      to introduce a fluorescent antibody, are described. Following labelling, cells
      were evaluated for p21ras associated fluorescence by flow cytometry.
      Electroporation, sorting, and cell handling parameters were varied to determine
      optimal conditions for cell viability. Cells were best held in serum containing
      growth medium both before and after electroporation, while antibody introduction
      during the electroporation phase was most efficient when carried out in a
      balanced saline solution. For maximum efficiency of antibody internalization, the
      antibody needed to be present during electroporation, and medium needed to be
      replaced several times in the first few hours after electroporation to ensure
      good cell survival.

PMID- 1999125
TI  - An innovation in flow cytometry data collection and analysis producing a
      correlated multiple sample analysis in a single file.
AB  - The problems associated with rapid analysis and interpretation of data from
      multicolor immunofluorescence panels have been a formidable barrier to their
      routine use. Using present flow cytometry concepts, a panel of 11 tubes each
      containing multiple phenotypic markers or controls requires postdata acquisition
      manipulation of many multiparameter histogram and listmode files. We have
      developed a method that compresses all of the information from such a panel into
      a single listmode data file during run time. A single data file is used to record
      the entire phenotypic analysis for a particular patient or series within an
      experiment. This is accomplished by the incorporation of a tube identifier
      parameter (TIP) as well as the fluorescence and light scatter parameters normally
      collected. The TIP can then be used for gating discrimination of any tube or set
      of tubes within a panel. When the TIP is correlated with the PRISM parameter the
      entire patient phenotypic image can be represented within a single two-parameter
      histogram we have called a phenogram. This phenogram can be generated in real
      time, providing on-line preprocessing of a complex multicolor experiment. By
      examining the image created by the phenogram it is possible to rapidly flag
      abnormalities such as incorrect gating. This procedure was carried out on an
      EPICS Elite flow cytometer in its standard configuration with the addition of
      hardware to provide an input for the TIP.

PMID- 1999126
TI  - Incontinence and rectal prolapse: a prospective manometric study.
AB  - A prospective, manometric study has been performed on 23 female patients with
      rectal prolapse and varying degrees of incontinence. Seven of the 14 incontinent
      patients regained continence after surgery, and a further two patients improved.
      Improvement in internal and external sphincter function follows correction of
      rectal prolapse. Preoperative resting anal pressure was significantly higher in
      continent patients than in incontinent patients (P less than 0.05), as was the
      maximum voluntary contraction pressure (P less than 0.027). Postoperatively there
      was a significant increase in the resting anal pressure (P less than 0.0001) and
      maximum voluntary contraction pressure (P less than 0.003) in the whole group.
      The preoperative resting anorectal angle was significantly more acute (P less
      than 0.028) in continent patients than in incontinent patients. There was no
      significant change in the resting anorectal angle following prolapse repair.
      Patients who remained incontinent had a significantly lower preoperative resting
      anal pressure (P less than 0.01) than patients who improved or regained
      continence. Similarly, maximum voluntary contraction pressure was lower
      preoperatively in these patients (P less than 0.02). Preoperative resting anal
      pressure below 10 mm Hg and maximum voluntary contraction pressure below 50 mm Hg
      are associated with persisting incontinence after surgery.

PMID- 1999127
TI  - The value of radioimmunoguided surgery in first and second look laparotomy for
      colorectal cancer.
AB  - Radioimmunoguided surgery (RIGS) using an anti-CEA (A5B7) monoclonal antibody has
      been assessed in 52 patients (43 primary excisions and nine second look
      procedures) undergoing surgery for colorectal carcinoma. The antibody localized
      in 97.8 percent of primary tumours and in 88.8 percent of the principal tumor in
      second look procedures. Additional information concerning the extent of primary
      tumor was obtained in 11 of 43 patients (25.5 percent) undergoing excision of
      primary carcinoma and five of nine patients (55 percent) in the second look
      series. Incorrect information was obtained about the extent of the primary tumour
      in six patients (11.3 percent), whereas no incorrect information was obtained
      during second look procedures. RIGS correctly predicted the subsequent Dukes'
      staging in 77 percent of first look cases (sensitivity 65 percent, specificity 90
      percent), although accurate identification of individual nodes was impossible.
      The technique influenced the surgical procedure performed in 2 of 43 cases (4.6
      percent) in primary surgery and in three of nine patients undergoing second look
      laparotomy (33 percent). RIGS in primary colorectal carcinoma may provide
      additional information concerning extent of locally advanced tumors in particular
      and the principle that the subsequent surgery may be influenced has been
      established. The technique appears to have a greater role in second look
      procedures where it may help determine the extent of recurrent tumour. Larger
      follow-up series are required to define how the additional information provided
      by this technique may best be exploited.

PMID- 1999128
TI  - Postoperative irrigation-suction drainage after pelvic colonic surgery. A
      prospective randomized trial.
AB  - A 2-year randomized prospective clinical trial was undertaken to determine
      whether postoperative irrigation of the pelvis would result in a decreased
      incidence of local septic complications. Two hundred consecutive patients
      undergoing low pelvic procedures with rectal resection and entry of the presacral
      space by a single surgeon, were randomized. In the irrigation group, two of four
      presacral sump drains were placed to low intermittent suction and the remaining
      sumps infused continuously with saline until the effluent was clear. In the
      drainage alone group, all four presacral sump drains were placed to suction.
      Drains were removed when drainage was less than 50 ml/24 hours. Perioperative
      antibiotics and bowel preparation were identical. Postoperative complications
      included pelvic abscess (n = 7), anastomotic leak/cuff sinus (n = 11), abdominal
      wound infection (n = 19), and perineal wound infection (n = 5). Postoperative
      irrigation of the pelvis did not result in a reduction in the overall rate of
      local pelvic septic complications. Positive intraoperative presacral cultures,
      the presence of anaerobes in the presacral space, and duration of pelvic drainage
      had no effect on the development of pelvic sepsis.

PMID- 1999129
TI  - Vascular responsiveness in obstructed gut.
AB  - Multiorgan system failure due to hypotension and sepsis is an important cause of
      death in patients with bowel obstruction. We have investigated the
      pathophysiology of this entity in an animal model. After 5 days of bowel
      obstruction, blood flow in the superior mesenteric artery was measured with and
      without Pitressin and norepinephrine given in separate experiments. In controls,
      Pitressin in moderate dosages caused a substantial fall in gut blood flow, which
      was not seen in obstructed animals (blood flow reduction 52 percent vs. 11
      percent in sham and obstructed animals respectively, P less than 0.01).
      Similarly, norepinephrine infusion had less of an effect on gut blood flow in
      obstructed animals (blood flow reduction 79 percent vs. 58 percent sham vs.
      obstructed animals (P less than 0.05). Thus, both agents had dose-related effects
      on gut blood flow, which was maintained at a higher level throughout the drug
      infusion periods in the bowel of obstructed animals, demonstrating that
      splanchnic flow is less responsive to vasoactive drug infusion under these
      experimental conditions. Because splanchnic vasoconstriction is an important
      feature of normal hemodynamic homeostasis, we suggest that these results may help
      explain some aspects of the pathophysiology of multiorgan failure caused or
      worsened by systemic hypotension seen in bowel obstruction.

PMID- 1999130
TI  - The influence of NSAIDs on experimental intestinal anastomoses.
AB  - Limiting degradation of collagen during the initial phase of wound healing is
      expected to improve postoperative intestinal strength and thereby decrease
      chances for anastomotic dehiscence. We studied the influence of four nonsteroid
      anti-inflammatory drugs on the healing of intestinal anastomoses in rats, with
      special regard to changes of collagen levels around the anastomoses. Four
      experimental groups of 20 rats each received daily oral doses of piroxicam,
      ibuprofen, aspirin, or indomethacin and were compared with a control group.
      Animals were sacrificed 3 or 7 days after operation. Both morbidity and mortality
      rate in the experimental groups were high. Collagen, measured as hydroxyproline,
      levels in anastomotic and adjoining 1-cm intestinal segments were compared with
      concentrations in control segments resected during operation. After an initial
      decrease on day 3, hydroxyproline concentrations increased on day 7. In the colon
      the lowering of hydroxyproline concentrations, which was more pronounced than in
      the ileum, was significantly reduced by administration of piroxicam and
      ibuprofen, both in the anastomosis and its proximal segment. On day 7, the
      increase of hydroxyproline concentrations in the ileum was inhibited by
      administration of anti-inflammatory drugs. It is concluded that nonsteroidal anti
      inflammatory drugs may limit postoperative degradation of collagen in colonic
      anastomoses, but at the same time may increase the rat's susceptibility to
      surgical infections.

PMID- 1999131
TI  - Clostridium difficile--a common and costly colitis.
AB  - Clostridium difficile infection manifests as a self-limiting diarrhea, protracted
      colitis, or toxic pseudomembranous colitis. The incidence of C. difficile in a
      514-bed community hospital was studied retrospectively; 155 patients of a total
      18,262 admitted during 1988 were identified with C. difficile as an admitting or
      subsequent diagnosis. The method of diagnosis, mode of therapy, and related costs
      were analyzed. We have determined that education, with an emphasis on
      pathogenesis and prevention, is necessary to reduce the incidence in the hospital
      and the cost to the patient.

PMID- 1999132
TI  - Nuclear shape as a prognostic discriminant in colorectal carcinoma.
AB  - In search for a more reliable prognostic discriminant, a retrospective analysis
      of 100 cases of colorectal carcinoma having undergone curative resection and
      followed for at least 5 years were assessed by nuclear morphometry. Each case was
      staged according to the Dukes' classification as well as graded histologically.
      For all patients in this series, the perimeter, area, and nuclear shape factor of
      50 interphase nuclei were determined for each carcinoma. The information was
      obtained through the use of an image analysis system by tracing the nuclear
      profiles (magnification 1000x) as digitized on a video screen. The nuclear shape
      factor was defined as the degree of circularity of the nucleus, a perfect circle
      recorded as 1.0. A nuclear shape factor greater than 0.84 was associated with
      poor outcome. Multiple regression models showed that the single nuclear parameter
      of the shape factor was the most highly significant predictor of survival (P less
      than 0.0001). This variable remained highly significant even when corrected for
      sex, age, histologic grade, and Dukes' classification. These findings indicate
      that a nuclear shape factor greater than or equal to 0.84 as determined by
      nuclear morphometry is an independent morphometric nuclear variable of great
      importance in the prognosis of large bowel carcinoma.

PMID- 1999133
TI  - Hemorrhoidectomy during pregnancy: risk or relief?
AB  - Acute hemorrhoidal crisis can occur in the pregnant female. When medical therapy
      fails to relieve pain, operative intervention may be necessary. The surgeon,
      however, may be reluctant to operate due to potential complications to the mother
      and fetus. From July 1983 to July 1989, hemorrhoidectomy was performed in 25 of
      12,455 pregnant women (0.2 percent) who delivered in our institution. Twenty-two
      women were in their third trimester, 80 percent were multiparous, and each had a
      remote history of hemorrhoidal symptoms, including intermittent pain, bleeding,
      and protrusion. Closed hemorrhoidectomy was performed under local anesthesia. The
      surgery was directed at removing only symptomatic disease, which included three
      quadrants in 14 patients, two quadrants in seven patients, and one quadrant in
      four patients. All patients experienced relief of intractable pain the day after
      surgery, except one patient who required a hemostatic packing during the
      immediate post-operative period. There were no other maternal or fetal
      complications. Subsequent follow-up for anorectal disease ranged from 6 months to
      6 years. Six (24 percent) patients required additional hemorrhoid treatment.
      Hemorrhoidectomy in selected pregnant patients is safe in our experience.

PMID- 1999134
TI  - Development of the anal canal muscles.
AB  - The anal canal muscles development is studied in 18 human embryos. The external
      anal sphincter results to origin common with the urogenital sphincter from the
      cloacal sphincter. The muscle, after its appearance, is subdivided into two
      portions from a thin mesenchymal layer. Moreover, our embryologic study clearly
      confirms that the puborectalis muscle is a portion of the levator ani, its
      primordium being common with the ileo and the pubococcygeus muscles. The anal
      smooth musculature appears later than the striated one.

PMID- 1999135
TI  - Loop ileostomy after ileal pouch-anal anastomosis--is it necessary?
AB  - Construction of a loop ileostomy is usually advised in patients having an ileal
      pouch-anal anastomosis to minimize the complication of chronic pelvic sepsis.
      Formation and closure of a loop ileostomy was associated with a 41 percent and 30
      percent complication rate, respectively, in a prospective series of 34 patients.
      This morbidity must now be assessed in relation to the benefits of avoiding
      temporary fecal diversion in restorative proctocolectomy.

PMID- 1999136
TI  - Surgical treatment of low rectovaginal fistulas.
AB  - Forty women with low rectovaginal fistulas were operated upon over a 9-year
      period. The etiology of the fistula in the majority was obstetric. Nine women had
      prior attempts to repair the fistula. All 40 women were managed with endorectal
      advancement flap with the addition of sphincteroplasty or perineal body
      reconstruction in 15 patients and rectocele repair in six patients. Postoperative
      complications included urinary difficulties (two patients) and wound
      complications (three patients). There were two recurrences. All women treated
      with sphincteroplasty or perineal body reconstruction were continent. Seven women
      complained of varying degrees of incontinence postoperatively; none had undergone
      sphincter or perineal body reconstruction. Endorectal advancement flap is a safe
      and effective operation for women with rectovaginal fistulas. Concomitant
      sphincteroplasty or perineal body reconstruction should be performed in women
      with historical, physical, or manometric evidence of incontinence.

PMID- 1999137
TI  - Primary de novo adenocarcinoma of the colon measuring 8 mm in diameter with lymph
      node metastases. Report of a case.
AB  - Colonic adenocarcinomas measuring less than 10 mm are rare. Herein, we report a
      carcinoma measuring 8 mm in diameter associated with subserosal extension through
      a "locus minoris resistentiae" and metastases to lymph nodes, an association not
      previously reported. No residual adenomatous tissue was found, suggesting a de
      novo carcinoma.

PMID- 1999138
TI  - Dysplasia and DNA aneuploidy in a pelvic pouch. Report of a case.
AB  - A patient with an 18-year history of ulcerative colitis was operated on with
      colectomy, mucosal proctectomy, ileoanal anastomosis, and an S-type pelvic pouch
      due to intractable chronic continuous disease. The patient was followed by
      endoscopic controls and biopsy sampling from the pouch at regular intervals. A
      gradual development of severe atrophy in the ileal mucosa was followed by the
      development of low grade dysplasia. At the most recent endoscopic control, 4
      years after the construction of the pouch, biopsies were sampled also for flow
      cytometric DNA analyses. DNA aneuploidy was detected in a biopsy from the center
      of the pouch, and a biopsy taken immediately adjacent showed low grade dysplasia.
      These findings underline the importance of endoscopic follow-up after
      construction of a pelvic pouch and focus attention to the potential of malignant
      transformation of the mucosa.

PMID- 1999139
TI  - Sclerosis of the internal sphincter.

PMID- 1999141
TI  - New treatment of intractable pruritus ani.

PMID- 1999140
TI  - Pyrexia after anorectal surgery.

PMID- 1999142
TI  - Significance of the glycan moiety of the rat ovarian luteinizing
      hormone/chorionic gonadotropin (CG) receptor and human CG for receptor-hormone
      interaction.
AB  - The role of the glycan moiety of the rat ovarian LH/CG receptor and human CG
      (hCG) in high-affinity receptor-hormone interaction was investigated by cross
      linking and quantitative binding experiments. hCG and its derivatives,
      desialylated hCG and deglycosylated hCG were labeled either to the alpha-subunit
      (125I) or the beta-subunit (3H). The ligands were attached to ovarian membrane
      particles, which were treated with neuraminidase or peptide-N-glycosidase F to
      remove terminal sialic acids or N-linked oligosaccharides of the receptor,
      respectively, and the complexes formed were solubilized, cross-linked with
      glutaraldehyde, and analyzed by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. All of the ligands produced similar autoradiographic patterns
      with the native or glycosidase-treated receptor, and only the receptor-(alpha)hCG
      and receptor-(alpha, beta)hCG complexes were detected. Moreover, quantitative
      binding studies indicated that all of the hormone derivatives had similar
      affinities for the native or glycosidase-treated receptor. In addition, the
      orientation of the carbohydrate side chains on the receptor-hormone complex was
      studied by digesting the complex with the glycosidases. The molecular weight of
      the receptor, evidenced by ligand blotting, was reduced to the same extent,
      whether the membrane-bound free receptor or receptor-hormone complex was treated
      with the glycosidases, suggesting that the oligosaccharide side chains of the
      receptor are apart from the hormone binding region. As peptide-N-glycosidase F
      treatment reduced the size of the Mr 90,000 receptor first to about Mr 67,000 and
      finally to about Mr 62,000, there may possibly be 2 N-linked carbohydrate chains
      per receptor polypeptide. Sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis analysis of the glycosidase-treated receptor-[125I]hCG complex
      also revealed that neuraminidase was able to remove the sialic acids from both
      subunits of the receptor-bound hormone. In conclusion, the results suggest that
      hCG interacts with the polypeptide backbone of its ovarian receptor mainly
      through the peptide core of its alpha-subunit. Moreover, the carbohydrate side
      chains of both subunits of hCG are positioned on the outward face of the receptor
      hormone complex.

PMID- 1999143
TI  - Regulation of pulsatile luteinizing hormone secretion in experimental uremia.
AB  - Previous studies have shown that male rats with experimental uremia manifest
      profound suppression of circulating LH and testosterone levels, yet,
      paradoxically, after castration gonadotropin levels are elevated greatly above
      those of nonuremic castrate control rats. To investigate further this phenomenon,
      we characterized pulsatile LH secretion in experimental uremia. Mature
      orchidectomized male Wistar rats with subtotal nephrectomy demonstrated a 43%
      reduction of LH pulse frequency, but a 157% increase in pulse amplitude and a
      335% increase in mean LH levels compared with sham-operated controls. All pulse
      parameters were highly correlated with plasma creatinine (r = 0.53-0.75). To
      determine the mechanism of the increased pulse amplitude, we tested
      responsiveness of the postcastration uremic pituitary to exogenous GnRH (0.01-10
      micrograms/kg) in a Latin square design. Plasma LH response was linearly related
      to the logarithm of the GnRH dose in uremic and control rats, but was markedly
      increased in uremic rats. We conclude that the uremia causes decreased LH pulse
      frequency independent of testicular feedback. Pituitary hypersensitivity to GnRH
      magnifies LH pulse amplitude and thereby is the major factor causing the
      paradoxical LH hyperelevation after castration.

PMID- 1999144
TI  - On the transforming growth factor beta-like activity of synthetic polypeptides
      comprising the amino-terminal sequence of human parathyroid hormone-related
      peptide.
AB  - Purified native forms of human parathyroid hormone-related peptide (PTHrp) have
      recently been reported to display biological activities characteristic of
      transforming growth factor beta (TGF-beta). The TGF-beta-like property of PTHrp
      may reside within the amino N-terminal PTH-receptor binding region of the
      polypeptide, since a synthetic analog corresponding to amino acids 1-36 of human
      PTHrp is as active as purified native PTHrp in bioassays specific to TGF-beta.
      Complete lack of structural similarity between PTHrp and TGF-beta prompted us to
      address the question whether copresence of the TGF-beta-like and PTH-like
      biological activities in the N-terminal sequence of the PTHrp molecule is a
      general phenomenon observable with different N-terminal PTHrp peptides of varying
      amino acid chain length in a variety of target cells that respond in defined ways
      to TGF-beta in vitro. Two forms of synthetic N-terminal human PTHrp, PTHrp-(1-34)
      and [Tyr40]PTHrp-(1-40), which are fully active in conventional assays for
      PTH/PTHrp, were tested for effects in three in vitro bioassay systems for TGF
      beta: 1) stimulation, and 2) inhibition, respectively, of epidermal growth factor
      dependent soft-agar colony formation of either normal rat kidney-derived
      fibroblasts (NRK 49F) or human lung carcinoma cells (A549); and 3) biosynthesis
      of metabolically labeled fibronectin in both NRK 49F cells and clonal
      osteoblastic rat osteosarcoma cells (ROS 17/2.8). Human TGF-beta over the dose
      range of 2.5-80 pM significantly stimulated or inhibited soft-agar colony
      formation of either NRK 49F or A549 cells, respectively, and caused a severalfold
      increase in biosynthetically labeled [35S]fibronectin in NRK 49F and ROS 17/2.8
      cells. In contrast, none of PTHrp-(1-34), [Tyr40]PTHrp-(1-40), and synthetic
      human PTH-(1-34), each tested at 0.1-10 nM, displayed detectable biological
      activity in any of the three assay systems. In addition, covalent cross-linking
      of intact NRK 49F and ROS 17/2.8 cells with either [125I]TGF-beta or 125I-[Tyr40]
      PTHrp-(1-40) revealed the presence of several distinct affinity-labeled receptor
      species for TGF-beta in both cell types and the 80K PTH/PTHrp receptors in ROS
      17/2.8 cells. The affinity-labeled TGF-beta receptor species were insensitive to
      excess PTHrp and PTH peptides, and the 80K PTH/PTHrp receptors were insensitive
      to excess TGF-beta, indicating that PTHrp and TGF-beta do not cross-react with
      respect to receptor binding for interaction with these cells.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 1999145
TI  - Differential regulation of brain aromatase by androgen in adult and fetal
      ferrets.
AB  - The contribution of androgens to the regulation of aromatase activity (AA),
      measured by quantifying the in vitro formation of [3H]estrone from 19
      [3H]hydroxyandrostenedione precursor, was studied in equivalent microdissected
      brain regions of adult and fetal ferrets. In adulthood, AA was similar in the bed
      nucleus of the stria terminalis, medial (M) and lateral (L) preoptic area (POA),
      medial (MA) and lateral amygdala (LA), ventromedial hypothalamus (VMH), and
      parietal cortex of gonadectomized males and females given no concurrent steroid
      treatment. Daily sc injections of the androgen dihydrotestosterone propionate
      significantly stimulated AA in MPOA, MA, and VMH of adult males and in MA of
      females; a similar trend was seen in MPOA and VMH of females. By contrast, no
      evidence of androgenic regulation of AA was obtained in these three brain regions
      microdissected from fetuses killed on embryonic day 35 (E35; 41-day gestation).
      Transplacental administration of the antiandrogen flutamide beginning on day E24
      failed to affect AA in MPOA, LPOA, MA, LA, or parietal cortex, although this
      treatment significantly reduced AA in bed nucleus of the stria terminalis of
      fetal males. The results suggest that the responsiveness of aromatizing enzymes
      to androgenic induction is similar in several subcortical brain regions of adult
      ferrets of both sexes. In breeding males such an action of androgen may augment
      the neural production of estrogen, which has previously been implicated in the
      control of sexual behavior and the feedback regulation of LH secretion. By
      contrast, androgen apparently contributes minimally to the regulation of AA in
      brain regions of fetal ferrets, particularly in the MPOA, in which a sexually
      dimorphic nucleus differentiates in males around E37 in response to estrogen
      produced locally.

PMID- 1999146
TI  - Changes in proopiomelanocortin messenger ribonucleic acid levels in the rostral
      periarcuate region of the female rat during the estrous cycle.
AB  - GnRH synthesis and release are regulated by a number of neurotransmitter systems.
      Several studies have implicated the opioidergic system as one of the important
      modulators of GnRH. To obtain an index of the activity of beta-endorphin
      secreting neurons during the estrous cycle, we measured levels of
      proopiomelanocortin mRNA (POMC mRNA) in the periarcuate region at different cycle
      stages, using in situ hybridization. Ten female Sprague-Dawley rats (200-230 g)
      were killed at each of 11 times during the 4-day estrous cycle. Fresh frozen
      sections were made through the rostral arcuate nucleus and placed on gelatin
      coated slides. A 48-base probe complementary to rat POMC mRNA was 3' end-labeled
      with [35S]dATP and applied to individual sections in hybridization buffer.
      Sections were washed and exposed to film. Relative amounts of POMC mRNA were
      measured by obtaining optical densities with an image analyzer. POMC mRNA levels
      varied significantly. At proestrus, they were low just before the onset of the LH
      surge, followed by a sharp rise that afternoon. On the day of estrus, POMC mRNA
      remained elevated and then declined again on metestrus. A second but smaller rise
      was seen in the late afternoon of metestrus. This pattern of changes in POMC mRNA
      is consistent with an inhibitory effect of beta-endorphin on GnRH after the
      midcycle surge and in the postovulatory phase of the cycle, while low levels of
      POMC mRNA in the early afternoon of proestrus may permit the release of GnRH,
      which triggers the LH surge. The changes in POMC mRNA approximately parallel
      changes in progesterone in the cycle.

PMID- 1999147
TI  - Variable phosphate-mediated regulation of vitamin D metabolism in the murine
      hypophosphatemic rachitic/osteomalacic disorders.
AB  - The familial hypophosphatemic (vitamin D-resistant) disorders are a variety of
      genetic and acquired syndromes that exhibit unexpected biochemical heterogeneity,
      manifest as variably abnormal or apparently normal regulation of 1,25
      dihydroxyvitamin D [1,25-(OH)2D] production. Recently, we observed that Hyp and
      Gy mice, murine homologs of X-linked hypophosphatemic rickets, exhibit similarly
      disparate regulation of vitamin D metabolism. While Gy mice under basal
      conditions maintain an appropriate elevation (relative to hypophosphatemia) of
      renal 25-hydroxyvitamin D (25OHD)-1 alpha-hydroxylase, Hyp mice manifest only
      normal, not increased, enzyme activity. Whether such diversity results from
      maintenance of phosphate (P)-regulated 1,25-(OH)2D production in Gy mice and loss
      of this function in Hyp mice or from other variations remains unknown. Therefore,
      we examined the integrity of P-regulated enzyme activity in the Gy and Hyp mice
      by testing the effects of enzyme inhibition and alteration of the serum
      phosphorus concentration on 1,25-(OH)2D production. Initially, we discovered that
      inhibition of renal 25OHD-1 alpha-hydroxylase suppressed enzyme function in Hyp
      mice, but did not prevent expression of P-mediated activity in Gy mice. In this
      regard, while administration of a high calcium diet or 1,25-(OH)2D (0.4 ng/h, sc,
      for 48 h) resulted in a comparable inhibition of enzyme activity in Hyp (5.9 +/-
      0.5 vs. 2.8 +/- 0.7 fmol/mg.min) and normal mice (4.4 +/- 0.6 vs. 2.0 +/- 0.2
      fmol/mg.min), similar treatment did not effect complete inhibition of 25OHD-1
      alpha-hydroxylase in Gy (10.3 +/- 0.6 vs. 4.9 +/- 0.3 fmol/mg.min) or P-depleted
      mice (10.2 +/- 0.5 vs. 5.1 +/- 0.4 fmol/mg.min). In accord with the apparent
      persistence of P-mediated stimulation of enzyme function in Gy mice, dietary P
      repletion in this mutant resulted in a serum phosphorus concentration similar to
      that of normal mice and decreased enzyme activity (4.0 +/- 0.8 fmol/mg.min) to a
      level no different from that expressed in controls (3.4 +/- 0.3 fmol/mg.min).
      However, in the absence of apparent P-mediated stimulation of enzyme activity,
      identical treatment of Hyp mice increased the serum phosphorus level comparably,
      but paradoxically enhanced 25OHD-1 alpha-hydroxylase (3.1 +/- 0.4 vs. 11.7 +/-
      2.0 fmol/mg.min). Collectively, these data indicate that enhanced renal 25OHD-1
      alpha-hydroxylase expressed in Gy mice and probably in related human diseases
      results from normally maintained P regulation of enzyme activity, an action
      absent or mutated in the genetically distinct Hyp mouse.

PMID- 1999148
TI  - The effect of sodium intake on angiotensin content of the rat adrenal gland.
AB  - To determine whether dietary sodium intake modifies the generation of adrenal
      produced angiotensins and/or their relative proportions, Sprague-Dawley rats were
      maintained on a low (0.02%), normal (0.4%), or high (1.5%) sodium intake for 5
      days. The animals were then killed by decapitation at 0900 h, and their adrenal
      glands were removed and dissected into two parts: capsular tissue, containing the
      zona glomerulosa (ZG), and the decapsulated adrenal gland. The tissue was frozen
      in liquid nitrogen and extracted, and the individual angiotensins [angiotensin-II
      (AII), angiotensin-III (AIII), angiotensin-I (AI), and Des-Asp-angiotensin-I (Des
      Asp-AI)] were separated by HPLC and quantitated by RIA. On a normal sodium
      intake, the molar contents of the four angiotensins were similar in ZG, ranging
      from 3.1-6.6 pmol/g, although AII was present in a 60-70% higher concentration
      than AIII. In the decapsulated adrenal, the concentrations of the various
      angiotensins were again similar, but the absolute levels (per g tissue) were
      significantly (P less than 0.02) less than those in the ZG layer. With sodium
      restriction, the AII content increased more than 2-fold in the ZG, but not in the
      decapsulated adrenal tissue. In contrast, both AI and Des-Asp-AI significantly (P
      less than 0.01) decreased with sodium restriction, so that their contents on the
      low salt diet were only 15-20% of those observed on the high sodium diet. Thus,
      there was an inverse correlation (P less than 0.001) between the salt content of
      rat chow and the AII content of the ZG. The correlation between salt intake and
      AI as well as Des-Asp-AI levels was direct and significant (P less than 0.02).
      The AIII level in the ZG was similar on all diets. After a lag period, ZG AII
      increased sharply between 16-48 h of sodium restriction. These data document that
      sodium intake has a profound effect on the angiotensin content of the ZG, with
      sodium restriction substantially increasing the levels of AII while reducing the
      level of its substrate, AI. This also appears to be unique for glomerulosa cells,
      as in the decapsulated adrenal gland there is little if any change with sodium
      restriction. We conclude that these sodium-mediated changes in tissue AII
      production may be involved in the increased responsiveness of glomerulosa cells
      to aldosterone secretagogues during sodium restriction.

PMID- 1999149
TI  - Effect of relaxin on mammary development in ovariectomized pregnant gilts.
AB  - The role of relaxin in mammary development was studied between days 80-110 of
      pregnancy in ovariectomized gilts given progesterone to maintain pregnancy. To
      obtain an objective measurement of lobulo-alveolar (parenchymal) composition,
      mammary glands were cut in cross-section through the teat, and the area of
      parenchymal tissue on the exposed face of the gland was determined. Ovariectomy
      on day 80 or 100 followed by progesterone replacement therapy resulted in a
      dramatic reduction in the rate of growth of mammary parenchymal cross-section
      area on days 100 and 110 of gestation, respectively, compared to that in
      controls. In contrast, progesterone plus relaxin therapy, with highly purified
      porcine relaxin, restored the mammary parenchymal cross-section area to control
      values in ovariectomized gilts. Morphometric analysis of mammary tissue on day
      110 of pregnancy indicated that both the absence of relaxin after ovariectomy and
      replacement therapy with porcine relaxin in ovariectomized gilts had little if
      any effect on the percentages of the lumen, stroma, or epithelial that comprised
      the mammary parenchyma. It is concluded that relaxin has a stimulatory effect on
      the growth of mammary parenchymal tissue during late gestation in the pig.

PMID- 1999150
TI  - Marked seasonal changes in response to the negative feedback action of estradiol
      on luteinizing hormone secretion in the female Japanese monkey.
AB  - The seasonal changes in response to the negative feedback action of estradiol on
      LH secretion were studied in two groups of ovariectomized Japanese monkeys
      (Macaca fuscata fuscata; n = 6). Blood samples were collected two to three times
      a week, and changes in serum concentrations of LH, estradiol, and progesterone
      were examined. Before ovariectomy (OVX), serum LH was maintained at about 320
      pg/ml regardless of the season (breeding season: autumn and winter). After OVX
      and simultaneous treatment sc with a Silastic implant of estradiol during the
      first breeding season, serum LH increased rapidly and remained high. As spring
      arrived, serum LH decreased abruptly and remained low. The removal of implants
      during the subsequent nonbreeding season resulted in an increase in serum LH
      similar to that during the previous breeding season after OVX and estradiol
      treatment. After the reinsertion of implants during the same nonbreeding season,
      serum LH reverted to previous low levels. As autumn arrived (second breeding
      season), serum LH rose again and remained high under the presence of implants. In
      the first subset of animals (n = 3), the implants were left in place until the
      subsequent mid-nonbreeding season when they were removed, and reinserted during
      the same non-breeding season. The findings closely corresponded to the previous
      results. In these animals, the implants were removed during the third breeding
      season, which resulted in a significant increase in serum LH. The second subset
      of animals (n = 3) underwent removal of implants during the second breeding
      season, which resulted in a further increase in serum LH, but the difference was
      not significant. In both subsets of animals, the timing of the increase and
      decrease in serum LH under the presence of implants virtually coincided with the
      onset and end of the breeding season in ovary-intact animals. Serum estradiol
      after OVX was maintained at levels similar to those in intact animals (80-100
      pg/ml) under the presence of implants, but removal of implants resulted in
      decrease in serum estradiol to around 30 pg/ml within 1 week. Serum progesterone
      after OVX was maintained at low levels (less than 0.2 ng/ml) regardless of the
      presence of estradiol implants. These results clearly indicate a marked seasonal
      difference in serum LH concentrations in ovariectomized monkeys in response to
      constant serum estradiol. It is suggested that seasonal breeding of the Japanese
      monkey is governed by biannual changes in the response of the hypothalamo
      hypophysial axis to the negative feedback action of estradiol.

PMID- 1999151
TI  - Human growth hormone-variant is a biologically active somatogen and lactogen.
AB  - The human GH-variant (hGH-V) gene, a member of the GH-PRL gene family, is
      expressed by the placenta during the second and third trimesters of gestation.
      The secreted hGH-V protein differs from pituitary GH (hGH-N) by only 13 amino
      acids. We have previously demonstrated that hGH-V can bind to both somatogen and
      lactogen cell surface receptors in vitro, but that the ratio of its somatogen to
      lactogen receptor-binding affinities is substantially higher than that of hGH-N.
      We now characterize the somatogen and lactogen bioactivities of hGH-V and
      contrast them to the bioactivity of hGH-N. Somatogen bioactivity was assayed by
      stimulation of weight gain in hypophysectomized rats, and lactogen bioactivity
      was assayed by the mitogenic response of the Nb2 lymphoma cell line. While the
      average increase in rat body weight in response to a fixed concentration of
      hormone was comparable using either hGH-V or hGH-N, the mitotic response of the
      lactogen-inducible Nb2 cells was significantly less for hGH-V. The comparable
      somatogen, but lower lactogen, bioactivity of hGH-V relative to hGH-N parallels
      the previously reported receptor binding profiles of the two hormones and
      suggests that hGH-V has the potential to perform a unique role during human
      gestation.

PMID- 1999152
TI  - Sex differences in androgen receptors and aromatase activity in microdissected
      regions of the rat brain.
AB  - Males are generally more responsive than females to the behavioral and
      neuroendocrine actions of androgens. The present experiments were performed to
      determine whether these differences may result from sex differences in the number
      of androgen receptors (AR) in specific brain areas. For this reason, AR binding
      was compared in both cytosol (ARc) and cell nuclear KCl extracts (ARn) from
      microdissected brain regions of gonadectomized male and female rats treated with
      doses of testosterone (T) that produced equivalent physiological circulating
      androgen levels. In addition, microsomal aromatase activity was measured as a
      biochemical index of tissue responsiveness to T, since estrogen formation in
      certain brain areas is regulated by androgen. One week after exogenous T
      administration, males exhibited significantly higher levels of ARn than females
      in the bed nucleus of the stria terminalis, periventricular preoptic area, and
      ventromedial nucleus. Males also had significantly higher aromatase levels in
      these same areas plus the medial preoptic nucleus and anterior hypothalamus.
      There were no significant differences in ARn concentrations in eight other nuclei
      that were examined for significant sex differences in ARc levels observed under
      these experimental conditions. When ARc levels were compared in untreated
      gonadectomized male and female rats, males had greater levels of ARc in the bed
      nucleus of the stria terminalis only, indicating that new receptor synthesis may
      be responsible for the sex differences observed in T-treated rats. These results
      suggest that sex differences in neural responsiveness to androgens may be due in
      part to sex differences in ARn occupation in specific brain regions.

PMID- 1999153
TI  - Expression of insulin-like growth factor-I during chicken development.
AB  - We have investigated the expression of insulin-like growth factor-I (IGF-I)
      during ontogeny in the chick. IGF-I mRNA was first detectable in whole embryos on
      day 6, while serum IGF-I could be measured on day 9, the earliest time point
      examined. Serum IGF-I values rose 10-fold from about 3 ng/ml on day 10 to a
      prehatch peak of 30-35 ng/ml during days 15-17, and then declined to about 10
      ng/ml at the time of hatching. On days 17 and 20 of incubation, IGF-I mRNA was
      detected in eye, skeletal muscle, and brain, but could not be found in liver or
      heart until after hatching. During the posthatch period, serum IGF-I rose from 10
      ng/ml in the first week to 35-40 ng/ml during weeks 3-6, and liver IGF-I mRNA
      increased nearly 5-fold from weeks 1-7. The increases observed during weeks 1-3
      correlated with a posthatch rise in serum GH from 21 to 37 ng/ml, although GH
      levels declined over the subsequent 4 weeks without an appreciable change in
      serum IGF-I values. By contrast, before embryonic day 12 no GH could be detected
      in the circulation, while IGF-I was 19 ng/ml on day 11. These observations
      suggest that there is both GH-dependent and GH-independent regulation of IGF-I
      gene expression in the chick, as has been found in mammals, and support the idea
      that IGF-I plays a role in chicken embryonic development.

PMID- 1999154
TI  - Corticotropin-releasing factor modulates the immune response to stress in the
      rat.
AB  - We examined the role of CRF, a key mediator of the endocrine response to stress,
      in modulating immunosuppression during the subacute stress of intermittent
      electrical shock over 1 h. Administration of shock to intact rats resulted in a
      74% decrement in T-lymphocyte proliferation and a 59% decrease in natural killer
      cytotoxicity. Similar suppression of these two parameters of immune function in
      response to shock was noted in adrenalectomized rats as well. The
      immunosuppressive effects of this shock were significantly and comparably blunted
      when both intact and adrenalectomized animals were pretreated 1) iv with either a
      highly potent polyclonal CRF antibody or a specific CRF antagonist or 2)
      intracerebroventricularly with either a high affinity monoclonal antibody to CRF
      or a specific CRF antagonist. An immunomodulatory role for CRF is further
      supported by the findings that administration of exogenous CRF, either iv (10
      micrograms/animal) or intracerebroventricularly (1 microgram/animal), resulted in
      significant decrements in lymphocyte proliferation and natural killer
      cytotoxicity, similar to those seen with the stress paradigm. Our observations
      indicate that CRF plays a significant role in modulating the immune response to
      subacute stress, largely by adrenal-independent mechanisms.

PMID- 1999155
TI  - Role of the thyroid gland in seasonal reproduction: thyroidectomy blocks seasonal
      suppression of reproductive neuroendocrine activity in ewes.
AB  - Seasonal reproductive transitions in ewes are generated endogenously and are
      synchronized by annual changes in photoperiod. Previous evidence indicates that
      thyroidectomy prevents the transition to anestrus in ewes maintained in a fixed
      day length, suggesting that the thyroid is needed for endogenously generated
      reproductive arrest. Here we tested the hypothesis that the thyroid is required
      for endogenous seasonal suppression of the neuroendocrine mechanism that
      regulates pulsatile LH secretion. Ewes were thyroidectomized (n = 6) in summer, 6
      weeks before the onset of the breeding season, or they remained thyroid intact (n
      = 6). They were housed in a simulated natural photoperiod until the winter
      solstice; thereafter, they remained on that photoperiod (10 h of light, 14 h of
      darkness). To monitor pulsatile LH secretion, the ewes were ovariectomized and
      implanted with estradiol, and LH was measured in both frequent (every 6 min for 4
      h) and infrequent (twice weekly) blood samples. In this model, high LH indicates
      low response to estradiol negative feedback and reproductive induction; low LH
      signifies high response to estradiol negative feedback and reproductive arrest.
      LH levels (samples twice weekly) rose some 50-fold in both groups concurrently at
      the start of the breeding season in September. Frequent sampling in midbreeding
      season (autumn) revealed that both thyroidectomized and thyroid-intact ewes
      exhibited frequent LH pulses, with no group difference, in either the presence or
      absence of the estradiol implant. A marked group difference, however, emerged at
      the end of the breeding season. LH fell to basal values in thyroid-intact ewes
      (onset of low values Feb 3 +/- 8 days), whereas levels remained elevated in
      thyroidectomized ewes through the end of the study (April 26). At this time,
      thyroidectomized ewes had more frequent LH pulses than thyroid-intact ewes both
      in the presence and absence of estradiol. The circadian pattern of melatonin
      secretion and the seasonal change in PRL were found to be unaffected by
      thyroidectomy. These observations support the hypothesis that the thyroid is
      necessary for endogenous suppression of neuroendocrine mechanisms that generate
      LH pulses, a suppression crucial for the transition to anestrus.

PMID- 1999156
TI  - A proposed role for chromogranin A as a glucocorticoid-responsive autocrine
      inhibitor of proopiomelanocortin secretion.
AB  - Chromogranin A (CgA) is a 50 kilodalton (kDa) acidic glycoprotein that is
      costored and cosecreted from secretory granules with endogenous hormone from
      diverse endocrine cell types. The physiological role(s) of CgA is yet to be
      defined. In this study we used the AtT-20 mouse corticotropic cell line, which
      produces both CgA and POMC-derived peptides, to study 1) the regulation of CgA
      and POMC synthesis and secretion, and 2) the influence of CgA on POMC secretion.
      To study regulation of CgA and POMC biosynthesis and secretion, cells were
      treated with dexamethasone (DEX) or CRF for 48 h and CgA and POMC messenger RNAs
      and proteins were analyzed. Exposure to DEX for 48 h (10 nM) inhibited secretion
      of the 16 K fragment of POMC by 60% while stimulating CgA secretion 500% of
      control value. Consonant with these changes in protein, POMC mRNA levels fell to
      40% of control levels while CgA mRNA levels increased to 250% of control values
      with DEX treatment. DEX treatment had no effect on the sizes of the CgA [2.1
      kilobase (kb)] and POMC (1.0 kb) mRNAs. CRF (100 nM) stimulated secretion of both
      CgA (4-fold) and ACTH (2.5-fold) above basal values. By contrast, CRF increased
      POMC mRNA levels but had no effect on levels of CgA mRNA. Changes in total
      peptide production paralleled the changes in mRNA levels. Because DEX
      differentially regulated CgA and POMC synthesis and secretion, we questioned
      whether CgA could function as an autocrine inhibitor of hormone secretion. CgA
      inhibited CRF-stimulated secretion of 16 K fragment in a concentration-dependent
      manner (100% at 100 nM) without affecting basal 16 K fragment secretion.
      Moreover, anti-CgA antiserum, but not nonimmune serum, increased basal 16 K
      fragment secretion 2-fold and CRF-stimulated 16 K fragment secretion 1.5-fold.
      These results suggest that CgA plays an autocrine role as a glucocorticoid
      responsive inhibitor of POMC-derived peptide secretion.

PMID- 1999157
TI  - Enhancement of in vivo humoral immunity by estrogen: permissive effect of a
      thymic factor.
AB  - Physiological levels of estrogen enhance humoral immune responses. Several in
      vitro studies indicate the hormone to have a direct effect on immune cells, and
      other studies show that estrogen may affect humoral immunity indirectly through
      the thymus. Therefore, we have conducted experiments to investigate the
      requirement of the thymus in the enhancement of humoral immune responsiveness by
      estrogen. In Exp I, adult ovariectomized Lewis rats were thymectomized or sham
      thymectomized and given estradiol (E2; 0.25 microgram E2 in sesame oil, sc, once
      every 4 days) or the oil vehicle in a 2 x 2 factorial design, and their
      antifluorescein responses were followed by enzyme-linked immunosorbant assay
      across 21 days. Only animals that were thymus intact and given estrogen
      replacement showed significantly (P less than 0.05) greater serum antifluorescein
      titers than all other treatments. In Exp II, ovariectomized thymectomized rats
      were submitted to a 2 x 3 factorial design of oil vehicle or E2 replacement and
      saline, gelatin, or thymus replacement (thymosin fraction 5; 1 mg/kg in saline,
      sc). As described above, only the animals receiving both thymosin fraction 5 and
      E2 replacement displayed antifluorescein titers that were significantly (P less
      than 0.03) increased over titers of all other treatment groups. These results
      indicate that the enhancement of in vivo humoral immunity by estrogen requires
      the thymus, and that a constitutive thymic factor, found in thymosin fraction 5,
      exerts a permissive influence on the action of E2 outside the thymus to increase
      a specific humoral immune response.

PMID- 1999158
TI  - Cyclosporin-A increases synthesis of 1,25-dihydroxyvitamin D3 in the rat and
      mouse.
AB  - We have previously observed elevated serum 1,25-dihydroxyvitamin D3 [1,25-(OH)2D]
      levels in male rats treated with oral cyclosporin-A (CsA). This elevation was
      independent of changes in PTH, ionized calcium, or phosphate. This paper
      investigates the potential sources and mechanisms for this increase in both rats
      and mice. Kidney homogenates from rats treated for 14 days with (15 mg/kg) had a
      significant increase in 25-hydroxyvitamin D (25OHD)-24-hydroxylase (24
      hydroxylase) activity (149 +/- 20 vs. 89 +/- 16 fmol/mg.min; P less than 0.05),
      but nonsignificant increases in 25OHD-1 alpha-hydroxylase (1 alpha-hydroxylase)
      activity compared to controls. Kidney homogenates from C57b16J mice after the
      administration of 30-50 mg/kg CsA for 3 days revealed a linear dose-related
      increase in renal 1 alpha-hydroxylase (r = 0.96; P less than 0.05), which became
      significant with doses of 30 mg/kg CsA or more (P less than 0.05). To investigate
      the source of this 1,25-(OH)2D production, serum 1,25-(OH)2D was measured before
      and 48 h after bilateral nephrectomy in rats receiving CsA for 16 days. The
      percent decrease in serum 1,25-(OH)2D values was not significantly different in
      CsA-treated and untreated rats (33.9 +/- 4.9% vs. 47.5 +/- 4.9%), indicating
      little or no contribution from nonrenal sources. Studies of MCRs and production
      rates (PRs) revealed that the elevated 1,25-(OH)2D values were due to enhanced
      production and not altered clearance (PR, 12.4 +/- 1.2 vs. 19.1 +/- 1.9
      fmol/mg.min; P less than 0.01). CsA increases 1 alpha-hydroxylase activity and
      produces significant elevations in serum 1,25-(OH)2D levels in both rats and
      mice. This increase may have an impact on bone mineral metabolism and immune
      modulation in postorgan transplantation patients.

PMID- 1999159
TI  - Differential expression of secretogranin II and chromogranin A genes in the
      female rat pituitary through sexual maturation and estrous cycle.
AB  - Secretogranin II (SgII) is a protein of pituitary secretory granules released by
      LHRH-stimulated gonadotrope cells. Estrogens and androgens are modulators of SgII
      release. Experiments were performed to determine the regulation of expression of
      the SgII gene in the female rat pituitary, during sexual maturation and according
      to the estrous cycle. Age- and cycle-related changes in SgII mRNA content were
      estimated through cytoplasmic slot blot; SgII content was determined by western
      blotting; maturation of the protein was controlled through [35S]sulfate labeling.
      Variations in chromogranin A (CgA), another protein of secretory granules, were
      analyzed in the same experimental conditions to assess the specificity of SgII
      regulation. The pituitary SgII concentration increased between days 7 and 21 (2.2
      fold) and then declined to the initial 7-day-old value. Simultaneously, the CgA
      concentration went through a maximum between days 14 and 21 and then strongly
      dropped to barely detectable levels in the adult pituitary. The SgII mRNA
      concentration followed roughly the same pattern as the protein. Moreover, the
      sulfation level remained constant between days 14 and 60. These results
      demonstrated a regulatory mechanism operating, during sexual maturation, on the
      SgII gene and not on the protein processing or on storage/release steps. In the 4
      day cycling females, the pituitary SgII mRNA and protein contents were the lowest
      during estrus. They then increased to their highest values in diestrus II.
      Moreover, the sulfation level of SgII was significantly higher during estrus than
      during any other stage. Due to its low content level, variations in pituitary CgA
      could not be demonstrated during the cycle.

PMID- 1999160
TI  - Calcium transport by plasma membranes from a glucose-responsive rat insulinoma.
AB  - Inside-out plasma membrane vesicles from a glucose-responsive rat insulinoma
      showed an ATP- and Mg2(+)-dependent uptake of Ca2+. The Km (concentration giving
      half-maximal activity) for Ca2+ was 60 nM. In the presence of 0.4 microM free
      Ca2+, the Km for ATP was 15 microM, and the Km for Mg2+ was 4 microM. Glucose (30
      mM) decreased Ca2+ uptake by 50%, while other insulin secretagogues had no
      effect, except for glyceraldehyde, which stimulated Ca2+ uptake. Calmodulin
      increased the uptake of Ca2+, while trifluoperazine and vanadate inhibited the
      uptake. The Ca2(+)- and Mg2(+)-dependent ATPase from this tumor has a 10- to 20
      fold higher requirement for Ca2+, which suggests that this enzyme is not
      responsible for Ca2+ transport, rather, Ca2+ transport activity represents only a
      small fraction of the total Ca2(+)-ATPase activity. The physiological importance
      of Ca2+ transport in insulin secretion is evident from the inhibition of Ca2+
      uptake by glucose, which leads to a decrease in Ca2+ efflux from the cell. This
      inhibition would lead to an increase in intracellular free Ca2+ and insulin
      release.

PMID- 1999161
TI  - Thyroxine increases epidermal growth factor levels in the mouse thyroid in vivo.
AB  - Immunoreactive epidermal growth factor (EGF) has been detected in the thyroid,
      which raises questions concerning the source of thyroidal EGF and what affects
      its levels. We therefore have examined the effects of manipulating thyroid
      function on the immunoreactive EGF levels in plasma, thyroid, submaxillary gland
      (SMG), and kidney of adult male BALB/c mice, and we also analyzed the prepro-EGF
      messenger RNA in these tissues. Groups of six mice received daily injection of T4
      (1 microgram, 5 micrograms, or 25 micrograms) or bovine TSH (1 mU) for up to 14
      days. The plasma EGF concentration was 0.31 +/- 0.01 ng/ml in control animals,
      and T4 (5 micrograms) decreased the plasma levels by about one-half within 1
      week. The thyroidal EGF was 0.50 +/- 0.14 ng/mg protein in control animals, and
      T4 (5 micrograms) increased the thyroidal EGF 8-fold within 1 week. There was a
      negative correlation between plasma and thyroidal EGF concentration (r = -0.93, P
      less than 0.01). Increasing doses of T4 also increased the SMG EGF content, while
      plasma levels fell (r = -0.88, P less than 0.01). The TSH treatment did not
      significantly alter the plasma or tissue EGF levels. Studies on mRNA prepared
      from these three tissues, using the reverse transcription and the polymerase
      chain reaction, indicated that the prepro-EGF mRNA was present in thyroid, SMG,
      and kidney. In conclusion, it appears that at least some thyroidal EGF is
      synthesized in the thyroid. Our observations that T4 increases the level of
      intrathyroidal EGF in a dose- and time-dependent fashion, while plasma levels
      fall, suggest the possibility that intrathyroidal EGF represents a shortloop
      feedback for the autocrine and/or paracrine regulation of thyroid function.

PMID- 1999162
TI  - Ethanol inhibits luteinizing hormone-releasing hormone release from the median
      eminence of prepubertal female rats in vitro: investigation of its actions on
      norepinephrine and prostaglandin-E2.
AB  - Recently, we have provided evidence that suggests that ethanol (ETOH) acts at the
      hypothalamic level to cause depressed serum LH levels and delay the onset of
      puberty in the female rat; however, the mechanism of this action is unknown.
      Thus, we evaluated the in vitro effects of ETOH on basal and stimulated LHRH and
      prostaglandin E2 (PGE2) secretion from the median eminence (ME) of prepubertal
      female rats. Brains were removed, and MEs dissected under a stereomicroscope,
      rinsed, and preincubated in Krebs-Ringer bicarbonate glucose buffer in an
      atmosphere of 95% O2-5% CO2 for 15 min. These media were discarded, and
      individual MEs were subjected to one of the following three experiments. In the
      first experiment, all MEs were incubated for 30 min in medium only. The media
      were collected and replaced in the control vials, again with medium only, or in
      the test vials with medium containing ETOH in doses from 15-70 mM. After this 60
      min incubation, the media again were collected, then replaced with the respective
      control or test medium, each containing norepinephrine (NE; 60 microM). Another
      experiment was conducted as described above, except that the MEs were challenged
      with PGE2 (2.8 microM) in place of NE. In both experiments the amount of LHRH
      released into these media was measured by RIA. In a third experiment, NE was used
      for the challenge; however, this time the amount of PGE2 released was measured by
      RIA. Our results indicate that ETOH did not alter basal LHRH release but,
      compared with controls, significantly blocked NE-induced LHRH release in a dose
      related manner. Conversely, ETOH had no effect on the PGE2-induced release of
      LHRH. Additionally, ETOH did not alter basal PGE2 release; however, it
      significantly blocked the NE-induced release of PGE2. We know that stimulation of
      LHRH release by NE is mediated by PGE2. Thus, these results suggest that the
      inhibitory effect of ETOH on LH release in the prepubertal female rat is due, at
      least in part, to the diminished secretion of LHRH resulting from altered PGE2
      release from within the ME.

PMID- 1999163
TI  - Interactions between steroid hormones and insulin-like growth factor-I in rabbit
      chondrocytes.
AB  - The mechanism of action of steroid hormones on skeletal growth is not understood
      in detail. We examined the interactions of steroid hormones and insulin-like
      growth factor-I (IGF-I) during DNA and sulfated proteoglycan synthesis in rabbit
      costal chondrocytes. Progesterone at 0.05 nM stimulated the incorporation of
      [3H]thymidine into DNA by 30% above the control level in confluent cultures, but
      neither testosterone nor 17 beta-estradiol stimulated DNA synthesis. None of the
      hormones affected [3H]thymidine incorporation stimulated by IGF-I when
      chondrocytes were incubated with one of the hormones and IGF-I simultaneously. In
      contrast, when confluent cultures were incubated with one of the sex steroids for
      24 h before the addition of IGF-I, stimulation of DNA synthesis by the growth
      factor was enhanced about 45% above the control value by 0.5 nM progesterone, 50%
      by 0.5 nM testosterone, and 80% by 50 nM 17 beta-estradiol. The effects of IGF-I
      on proteoglycan synthesis, as judged by the incorporation of [35S]sulfate, were
      stimulated by treatment with progesterone or testosterone. Dexamethasone at
      physiological concentrations inhibited chondrocyte DNA synthesis in confluent
      cultures to 10% of the control level. At 50 nM, dexamethasone suppressed IGF-I
      induction of DNA synthesis by 60%. This suppression was greater when
      dexamethasone was added before IGF-I than when the additions were simultaneous.
      When chondrocytes were treated with hydrocortisone or dexamethasone for 24 h
      before the addition of IGF-I, the glucocorticoids synergistically accelerated
      proteoglycan synthesis mediated by IGF-I. These findings suggest that steroid
      hormones have priming effects on the biological action of IGF-I in cartilage
      metabolism.

PMID- 1999164
TI  - Growth hormone (GH) receptors in clonal osteoblast-like cells mediate a mitogenic
      response to GH.
AB  - GH receptors have not hitherto been demonstrated or characterized on osteoblasts.
      In this study we report the characterization of functional GH receptors on the
      clonal rat osteoblast-like cell line UMR 106.06. The receptors have a typical
      somatogenic specificity, with high affinity for human GH, 10-fold lower affinity
      for rat GH, and very poor affinity for rat PRL. The affinity for rat GH is 1.2 +/
      0.4 x 10(9) M-1, and there are approximately 9000 receptors per cell. GH binding
      increased over several hours when incubations were carried out in serum free
      minimal essential medium, but binding reduced rapidly when incubations were
      carried out in Tris-NaCl-Mg++, HEPES, or bicarbonate buffer, suggesting a
      critical dependence of receptor expression on nutritional factors. Rat GH
      stimulated proliferation of UMR 106.06 cells in a dose-dependent fashion with a
      maximum 43 +/- 2% stimulation above control and half-maximal effect at a final
      hormone concentration of 15 +/- 3 ng/ml. A proliferative response was not
      observed at low cell density, suggestive of a requirement for a threshold
      concentration of autocrine mediators or density-dependent receptor expression. A
      monoclonal antibody (MAb 263) which blocks GH binding to a subset (type 1) of rat
      hepatic GH receptors did not block binding to osteoblast GH receptors, and did
      not block the proliferative response. Thus, the proliferative response appears to
      be mediated by a class of GH receptors not blocked by MAb 263 and possibly
      related to the type 2 hepatic GH receptors. RNA was extracted from UMR 106.06
      cells and a second osteoblast-like cell line UMR 201. Hybridization to a 32P
      labeled complementary DNA probe to the rabbit hepatic growth hormone receptor
      revealed two major labelled bands (3.5 and 1.2 kilobases) and one minor band (2.4
      kilobases) in both cell types. In summary, GH receptors are present in clonal
      osteoblast-like cells, and the receptors mediate a proliferative response to GH.
      The UMR 106.06 cells provide a valuable model system for studying the mechanism
      of GH action.

PMID- 1999165
TI  - Possible neuroendocrine actions of endothelin-3.
AB  - The presence of endothelin (ET) immunoreactivity and binding sites in
      hypothalamus and pituitary gland suggests potential neuroendocrine actions of
      this family of vasoactive peptides. ET-3, the predominant member of the ET family
      in brain, exerted significant dose-related (1, 10, and 100 nM) inhibitory effects
      on PRL release from dispersed anterior pituitary cells in static incubations. The
      effect was not dependent on voltage-sensitive calcium channels, since the
      dihydropyridine calcium channel antagonist nifedipine failed to block this
      action. Nifedipine did, however, significantly reduce the transient acute
      stimulatory effect of ET-3 on PRL release in cultured cells incubated in dynamic
      perifusion. The longer lasting inhibitory effect on PRL release that followed the
      brief stimulatory action was not affected by nifedipine. ET-3 also stimulated a
      transient but significant release of LH from cells harvested from random cycle
      female rats, an effect that was not antagonized by a LHRH antagonist, but was
      blocked by nifedipine, suggesting the mobilization of extracellular calcium as a
      mechanism of action of ET-3. Nifedipine also reversed the acute stimulatory
      effect of ET-3 on GH secretion from these cells. Cerebroventricular injections of
      ET-3 (6 or 60 ng) failed to significantly alter PRL or LH secretion in conscious
      rats, suggesting that brain-derived ET does not act within the hypothalamus to
      alter the release of these two hormones. Similarly, iv infusion of even pressor
      doses of ET-3 (10, 30, or 300 ng) failed to significantly alter PRL, LH, or GH
      release; thus, it is unlikely that ET of peripheral origin acts within the gland.
      Our results suggest that locally produced ET may act as a neuroendocrine or
      paracrine factor controlling pituitary function in the rat.

PMID- 1999166
TI  - Transcriptional regulation of ferritin messenger ribonucleic acid levels by
      insulin in cultured rat glioma cells.
AB  - Recent data have shown that ferritin, a ubiquitous protein, has a role as a
      regulator of cellular differentiation. In the present study we have investigated
      the expression of ferritin mRNAs in cultured C6 cells, a rat glioma cell line, in
      response to insulin, which has an important role in cellular growth and
      differentiation. Insulin stimulated steady state levels of both ferritin heavy
      chain and ferritin light chain mRNAs. An increase in the level of ferritin heavy
      or light chain mRNA was detected after 2 h of incubation with insulin, and a
      plateau was reached after 48 h for heavy chain mRNA and after 72 h for light
      chain mRNA. The responses were dose-dependent and were maximal at 100 nM for both
      mRNAs. Treatment of cells with actinomycin-D showed that insulin had no effect on
      the posttranscriptional stability of these mRNAs. Actinomycin-D inhibited insulin
      induced accumulation of both mRNAs, suggesting transcriptional stimulation of
      ferritin genes by insulin. A nuclear run-on assay showed that the insulin-induced
      increase in ferritin heavy chain mRNA was due to an increase in the rate of gene
      transcription. We also demonstrated that insulin-like growth factor-I (IGF-I)
      increased ferritin heavy and light chain mRNA levels in a dose-dependent fashion,
      and that the maximum effect was obtained at a concentration of 10 nM on both mRNA
      levels. IGF-I was not only 10-fold more potent, but the absolute level of maximum
      stimulation was also about 2-fold greater than that for insulin. The combination
      of insulin (100 nM) and IGF-I (10 nM) showed no additive effect. The results
      suggested that the ferritin heavy and light chain genes are transcriptionally
      regulated by insulin and influenced by IGF-I.

PMID- 1999167
TI  - Ontogeny of the endogenous stimulatory rhythm regulating prolactin secretion in
      immature female rats.
AB  - PRL secretion in the female rat is regulated by an endogenous stimulatory rhythm
      (ESR). This rhythm consists of two components: a nocturnal (N) component whose
      activity is greatest by 0300 h and a diurnal (D) component that peaks at
      approximately 1700 h. This periodicity coincides with the periods of the N and D
      surges of PRL in responses to the mating stimulus. Furthermore, we have shown
      that the ESR is involved in the regulation of mating-induced PRL surges. Mating
      causes a lowering of dopaminergic tone which reveals the ESR for PRL. The ability
      of immature female rats to express PRL surges induced by copulomimetic stimuli
      begins at 25 days of age. In this study we investigated the ontogeny of the ESR
      in immature female rats in order to observe the relationship between the onset of
      PRL secretion induced by copulomimetic stimuli and the development of the ESR.
      Immature female rats were raised in our colony and kept with their dams until
      used in an experiment or weaned at 23 days of age where appropriate. At 15, 20,
      23, 24, 25, or 30 days of age female rats received a single ip injection of
      domperidone (DOM; 5 mg/kg) or saline vehicle at 0300, 1200, or 1700 h. Thirty
      minutes after the injection the rats were decapitated, and trunk blood was
      collected. PRL was measured by RIA. DOM had no effect on PRL secretion as
      compared to that in saline-treated controls at 15 days of age. However, in all
      other age groups DOM induced a significant increase in PRL levels compared to
      those in saline-treated animals regardless of the time of injection. In addition,
      there was no time of day difference in the PRL secretory response to DOM in rats
      15-23 days of age. However, rats treated with DOM at 0300 h at 24 days of age
      secreted approximately 2-fold greater PRL than rats treated similarly at 1200 or
      1700 h. Moreover, at 25 and 30 days of age, rats treated with DOM at either 0300
      or 1700 h secreted significantly greater PRL than rats treated similarly at 1200
      h. These results suggest that the ESR for PRL secretion begins by 24 days of age.
      In addition, they indicate that the hypothalamic developmental event preceding
      and required for expression of mating-induced surges of PRL is the establishment
      of the ESR.

PMID- 1999168
TI  - Pleiotropic effects of vitamin D on osteoblast gene expression are related to the
      proliferative and differentiated state of the bone cell phenotype: dependency
      upon basal levels of gene expression, duration of exposure, and bone matrix
      competency in normal rat osteoblast cultures.
AB  - Normal rat osteoblasts in culture undergo a developmental sequence consisting of
      a proliferation period in which high levels of the histone and collagen type I
      genes are expressed, followed by periods of matrix maturation [high levels of
      alkaline phosphatase (AP)] and mineralization that signal a high level of
      production of osteopontin (OP) and osteocalcin (OC). Since these parameters are
      regulated by vitamin D, the effects of both short term and chronic treatment with
      1,25-dihydroxyvitamin D3 were examined during osteoblast growth and
      differentiation. In acute studies, during the proliferation period, histone mRNA
      (reflecting DNA synthesis) was inhibited (20-60%). Matrix Gla protein (MGP) and
      OP mRNA were significantly elevated during proliferation (30- and 15-fold), in
      contrast to OC which is not expressed and was not induced by hormone treatment.
      OP and MGP remained stimulated throughout the developmental sequence, but to a
      lesser degree (from 6- to 10-fold). Collagen and AP mRNA were inhibited by
      hormone at their peak levels of expression, but were stimulated at their lowest
      basal levels in the mineralization period. OC expression, which was initiated at
      the onset of mineralization, was stimulated 13- to 15-fold when basal levels were
      low, then from 6- to 8-fold by hormone throughout its period of expression. In
      chronic studies a different profile of gene expression was observed. When hormone
      treatment was initiated during the proliferation period on day 6, type I collagen
      and AP expression were suppressed, mineralized nodules did not develop, and
      induced levels of OP and OC gene expression did not occur. When chronic treatment
      was initiated on day 20 after the development of a mineralized matrix, OC, but
      not collagen and OP, levels were stimulated by the hormone. This observation is
      consistent with the requirement of a competent or mineralized bone matrix for
      expression of OC. In contrast, MGP expression was stimulated in the chronic
      vitamin D-treated cultures similar to acute treatments. Taken together these
      studies demonstrate that vitamin D, a physiological mediator of bone formation
      and remodelling, can both positively and negatively regulate expression of
      osteoblast phenotypic markers as a function of duration of hormone treatment and
      basal levels of gene expression, which is a reflection of bone matrix competency
      and the differentiated state of the osteoblast.

PMID- 1999169
TI  - On the possible role of the liver in the galactopoietic action of prolactin in
      the rat.
AB  - The possibility that the liver contributes to the galactopoietic effects of PRL
      was assessed in lactating rats in which endogenous PRL secretion was suppressed
      by injections of bromocriptine. Pup weight gain over a 5-day period (i.e. days 7
      12 of lactation) was used as an index of lactational performance in dams. Osmotic
      minipumps were used to infuse different doses of ovine (o) PRL into either the
      external jugular vein (JV) or the hepatic portal vein of the dams at a constant
      rate. The latter route of delivery would directly expose the liver to a higher
      concentration of PRL than would the former one. Twice daily sc injections of
      bromocriptine (1.5 mg/kg.injection) in corn oil into the dams completely
      suppressed litter weight gain. Infusion of oPRL into the JV at a dose of 2.0
      mg/rat.day restored lactation to normal in the drug-treated mothers.
      Electrophoretic analysis indicated that about 95% of the oPRL remained in the
      intact monomeric form when incubated in the infusion solvent in the minipump at
      37 C for 2 days, but by 4 and 6 days of incubation the amounts of that form
      decreased by about 25% and 50%, respectively. Measurement of serum oPRL levels by
      RIA showed that they were fairly constant, and after 5 days of infusion, the
      final concentration was directly related to the dose infused. Continuous infusion
      of oPRL into the JV was equally effective at restoring pup weight gain as was
      infusion into the hepatic portal vein over a wide range of doses. Hence, a
      physiological role of the liver in the maintenance of lactation by PRL is not
      supported by these experiments.

PMID- 1999170
TI  - Differential regulation of insulin-like growth factor-I (IGF-I) and IGF-II
      release from cultured neonatal mouse calvaria by parathyroid hormone,
      transforming growth factor-beta, and 1,25-dihydroxyvitamin D3.
AB  - In a previous study we found that PTH stimulated bone resorption and release of
      insulin-like growth factor-I (IGF-I) and IGF-II from cultured neonatal mouse
      calvaria. Since IGF-I and IGF-II stimulate osteoblast proliferation and collagen
      synthesis, these results suggested that increased release of IGFs during
      resorption could mediate in part coupling of bone formation to bone resorption.
      In the present study two other osteolytic agents, transforming growth factor-beta
      (TGF beta) and 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3 were examined for effects
      on IGF release from neonatal mouse calvaria. Like PTH, TGF beta stimulated
      resorption and increased release of IGF-I and IGF-II. 1,25-(OH)2D3, however,
      stimulated resorption and IGF-II release comparable to PTH, but inhibited release
      of IGF-I. 1,25-(OH)2D3 (0.1-100 nM) inhibited basal release of IGF-I, and 10 nM
      1,25-(OH)2D3 inhibited release of IGF-I induced by PTH or TGF beta. The effects
      of 1,25-(OH)2D3 were specific to this vitamin D metabolite and did not occur with
      25-hydroxyvitamin D3 or 24,25-(OH)2D3 at the same concentration. Calcitonin (50
      mU/ml) decreased 1,25-(OH)2D3 stimulation of resorption, but did not affect 1,25
      (OH)2D3 stimulation of IGF-II release and inhibition of IGF-I release. This
      evidence that effects of 1,25-(OH)2D3 on release of the IGFs were independent of
      bone resorption supports the conclusion that 1,25-(OH)2D3 modulated the
      production and secretion of IGF-I and IGF-II in calvarial cells. The results of
      this and the previous study suggest that PTH, TGF beta, and 1,25-(OH)2D3
      differentially regulate mouse calvarial cell IGF-I and IGF-II production.

PMID- 1999171
TI  - Suppression of pulsatile luteinizing hormone and testosterone secretion during
      short term food restriction in the adult male rhesus monkey (Macaca mulatta).
AB  - To determine whether signals occurring during the early stages of undernutrition
      can have a suppressive effect on the central drive to the reproductive axis, the
      effects of 1 day of fasting on pulsatile LH and testosterone secretion were
      examined in adult male rhesus monkeys. Monkeys were maintained with chronic
      indwelling venous catheters on tether/swivel systems. One day of fasting caused a
      small weight loss of 0.1-0.2 kg, which represented a loss of 1-3% of the initial
      body weight. On a day of normal feeding monkeys showed a mean of 4.57 +/- 0.53 LH
      pulses/12 h (measured from 1900-0700 h). On a subsequent day of fasting LH pulse
      frequency was significantly reduced to 1.86 +/- 0.46 pulses/12 h (P less than or
      equal to 0.05). Likewise, there was a similar decrease in testosterone pulse
      frequency on a day of fasting. The substantial decrease in LH/testosterone pulse
      frequency was not caused by the intensive blood-sampling regimen, in that
      collection of blood samples for 12 h on 2 consecutive days of normal feeding did
      not result in a decrease in either LH or testosterone pulse frequency.
      Administration of exogenous GnRH in doses of 0.05-0.3 microgram/kg caused LH
      pulses of similar magnitudes on a day of normal feeding and a day of fasting,
      suggesting that the decrease in LH pulse frequency during the day of fasting
      reflects a decrease in GnRH stimulation of the pituitary rather than a loss of
      pituitary sensitivity to GnRH. Measurement of pulsatile LH across 3 consecutive
      days (e.g. a day of normal feeding, a day of fasting, and a day of refeeding)
      indicated that LH pulse frequency is slow before the time that the meal is missed
      on the second day and remains low throughout the day of fasting (normal feeding,
      7 +/- 1.16 pulses/24 h; fasting, 3.33 +/- 0.33 pulses/24 h). Refeeding a normal
      meal at 1100 h on the third day resulted in an immediate and sustained increase
      in pulsatile LH secretion above normal frequency (11.07 +/- 0.33 pulses/24 h).
      These results indicate that very brief periods of undernutrition can
      significantly suppress the central drive to the reproductive axis in male rhesus
      monkeys, and this suppression can be rapidly reversed by refeeding. These
      findings argue against the hypothesis that undernutrition only suppresses central
      drive to the reproductive axis once a substantial amount of body weight has been
      lost.

PMID- 1999172
TI  - Monoclonal antiidiotypic antibodies interact with the 93 kilodalton thyrotropin
      receptor and exhibit heterogeneous biological activities.
AB  - Ten antiidiotypic monoclonal antibodies (AI mAb) reacting with the TSH receptor
      were produced by immunization of mice with a mouse mAb directed to a TSH epitope
      involved in the binding of the hormone to the receptor. The AI mAb were tested
      for their effects on the TSH receptor-adenylate cyclase system. Four AI mAb
      behave as agonists of TSH as they compete with TSH for binding to the receptor
      and stimulate the adenylate cyclase activity. Five AI mAb inhibited both TSH
      binding to the receptor and adenylate cyclase activity in the presence and
      absence of TSH; they were thus considered as antagonists of the hormone. One mAb
      inhibited only slightly the binding of TSH to the receptor and did not interfere
      significantly with the adenylate cyclase activity. The 10 AI mAb bound with
      various apparent affinities to solubilized thyroid membrane proteins but not to
      kidney, spleen, and liver membranes. Membrane desialylation did not significantly
      alter the binding of the AI mAb whereas deglycosylation modified more or less
      strongly the binding of mAb to thyroid membranes. It was also shown that the
      binding to solubilized thyroid membranes of the 10 mAb was inhibited by anti-TSH
      receptor autoantibodies present in patients with autoimmune disease. The mAb were
      further analyzed by Western blot analysis. One mAb did not react with the
      antigen, which suggested that it was directed to a conformational epitope. The
      other 9 mAb reacted with a protein of 70 kilodaltons and 5 revealed another band
      of 93 kilodaltons in accordance with the TSH receptor size deduced from the
      recently molecular cloning.

PMID- 1999173
TI  - Complete amino acid sequence analysis of a peptide isolated from the thymus that
      enhances release of growth hormone and prolactin.
AB  - We have previously reported that thymosin fraction 5 (TF5), a partially purified
      calf thymus preparation, contains a peptide(s) that can enhance the production of
      GH and/or PRL from rat anterior pituitary cells in vitro. Using reverse phase
      HPLC, we have now isolated and chemically characterized from TF5 a peptide
      possessing this activity. This peptide, termed MB-35, is a highly charged basic
      molecule of 35 amino acid residues and a mol wt of 3756. A computer-assisted
      search of published protein sequences has revealed that this peptide has a 100%
      homology with a region of the histone H2A. Biological studies using rat pituitary
      cells have revealed that MB-35 is active alone or in combination with GH
      releasing factor (GRF) or TRH and can increase the production of GH and/or PRL
      beyond that achievable with GH-releasing factor and TRH alone. The observation
      that histone H2A, the parent molecule, is without activity is of keen interest,
      since it suggests that nucleoproteins may have heretofore unknown physiological
      activities, perhaps related to cell cycle and/or other events associated with DNA
      activation events.

PMID- 1999174
TI  - Comparison of the effects of hypertonic sucrose and intracellular potassium
      depletion on growth hormone receptor binding kinetics and down-regulation in IM-9
      cells: evidence for a sequential block of receptor--mediated endocytosis.
AB  - To better understand the complex kinetics of human GH (hGH) binding to its
      receptors, we have further investigated, in IM-9 cultured human lymphocytes, the
      cellular locus corresponding to the slowly dissociating component of hormone
      binding, and to the homologous down-regulation of hGH receptors. First, we have
      detailed the biphasic kinetics of dissociation of bound hormone in control cells
      at 30 C. When the association at 30 C was extended from 0.5 to 3 h, the time
      required for half-dissociation of the fast component was slightly decreased (from
      30 to 15 min) but that of the slow component increased considerably (from 6 h to
      30 h). Concomitantly, the size of the slowly dissociating component increased
      from 50 to 80% of total. This indicates a maturation of bound hormone, from a
      rapidly to a slowly dissociating pool and, in the latter, an increase in the
      apparent affinity that may reflect a molecular rearrangement. Next, we have
      compared the effect of two procedures reported to inhibit receptor-mediated
      endocytosis at the level of coated pits. As previously reported, depletion of
      intracellular K+ abolished the slowly dissociating component and the down
      regulation of hGH receptors. In contrast, upon incubation with 0.4 M sucrose,
      which like K+ depletion virtually abrogated hGH internalization, the dissociation
      kinetics remained non-first order, and the down-regulation of hGH-receptor was
      only slightly reduced. Thus, these procedures appear to block receptor-mediated
      endocytosis at two successive compartments of the cell surface. In conclusion, we
      propose that some conformational change of hGH-receptor at the cell surface
      (possibly associated with clustering) may considerably slow down their
      dissociation and may be sufficient for down-regulation.

PMID- 1999175
TI  - Short exposure of rat pancreatic islets to interleukin-1 beta induces a sustained
      but reversible impairment in beta-cell function: influence of protease
      activation, gene transcription, and protein synthesis.
AB  - In an attempt to gain further knowledge about the mechanism of action of
      recombinant interleukin-1 beta (rIL-1 beta) on rat pancreatic beta-cells, we
      studied the effects of short term rIL-1 beta exposure (50 U/ml for 1 h) on islet
      function over the next 72 h. There was an initial increase in glucose-induced
      insulin release, followed by a decrease in islet function, reaching a nadir
      (values of insulin release about 20% of those observed in control islets) 10-12 h
      after treatment with the cytokine. Thereafter, the islets recovered their
      function, reaching levels of insulin secretion similar to the control values
      after 72 h. Short term exposure to rIL-1 beta did not induce a decrease in either
      islet DNA or islet insulin content. Using this experimental approach, we tested
      whether 1-h incubation of islets in the presence of various agents plus rIL-1
      beta could counteract the inhibitory effects of the cytokine 10-12 h later. Both
      actinomycin-D (5 micrograms/ml), an inhibitor of DNA transcription, and N alpha-p
      tosyl-L-lysine chloromethyl ketone (0.1 mM), a protease inhibitor, could protect
      the islets. There was also a weak protection by dimethyl urea (61 mM), a free
      radical scavenger, but no protection by cycloheximide (10 micrograms/ml), an
      inhibitor of protein synthesis, or amiloride (12.5 microM), a blocker of Na+/H+
      exchange. In a subsequent series of experiments, the islets were exposed for 6 h
      to different test agents after the initial 1-h exposure to rIL-1 beta. In this
      context, there was a clear protection by cycloheximide and actinomycin-D and a
      lesser protection by N alpha-p-tosyl-L-lysine chloromethyl ketone. These data
      suggest that early steps of the actions of rIL-1 beta on rat pancreatic islets
      are mediated by protease activation and gene transcription, followed by protein
      synthesis. The identity of the protein(s) remains to be clarified.

PMID- 1999176
TI  - Insulin stimulates synthesis and release of human chorionic gonadotropin by
      choriocarcinoma cell lines.
AB  - Recent studies have shown that insulin regulates placental lactogen,
      progesterone, and estrogen production from human trophoblast cells. This study
      was performed to examine whether insulin also regulates the production of hCG by
      this type of cell. After 24-36 h of preincubation, JEG-3 and JAR cells (2-3 x
      10(5) cells/ml.well) or human term trophoblast cells (1 x 10(6) cells/ml.well)
      were exposed to the test hormone in serum-free Dulbecco's Modified Eagle's Medium
      for 24-96 h. Secretion of hCG from JEG-3 cells was stimulated by human insulin,
      human proinsulin, or porcine insulin in a dose-dependent manner, with lowest
      effective doses of 6.7, 96, and 53 mg/L, respectively. Time-course studies showed
      that hCG secretion peaked at 72-96 h with insulin exposure; in contrast, no
      decernable peak was seen without insulin in serum-free media. Exposure of JEG-3
      cells for 24 h to 209 mg/liter insulin stimulated hCG synthesis, with 40 +/- 3%
      more immunoreactive intracellular hCG (P less than 0.05). Cells grown in the
      presence of insulin and [35S]methionine had 47 +/- 21% more labeled intracellular
      hCG and 56 +/- 13% more immunoprecipitable [35S]methionine-hCG secreted into the
      medium than the control cultures (P less than 0.05). During this time period,
      human placental lactogen release and total trichloroacetice acid-precipitable
      [35S]methionine protein were not increased. The insulin-induced stimulation of
      hCG synthesis was inhibited by cycloheximide. Additionally, insulin did not
      significantly affect total intracellular protein during 24-96 h of incubation.
      Insulin also increased hCG release from JAR cells, but not from human term
      trophoblast cells. A mouse monoclonal antibody to the IGF-I receptor inhibited
      the stimulation of insulin in JEG-3 cells. We conclude that insulin stimulates
      the synthesis and secretion of hCG from JEG-3 cells and JAR cells, and that hCG
      regulation in choriocarcinoma cells differs from that in primary human placental
      trophoblast cells. The effect of insulin on JEG-3 cells may be mediated in part
      through the insulin-like growth factor-I receptor.

PMID- 1999177
TI  - Mouse osteoblastic cells (MC3T3-E1) at different stages of differentiation have
      opposite effects on osteoclastic cell formation.
AB  - Using our new culture system for multinucleate cells (MNCs) that have many
      characteristics of osteoclasts, we examined the effects of factors produced by
      osteoblastic cells on osteoclastic cell formation. Conditioned medium (CM) from
      undifferentiated osteoblastic MC3T3-E1 cells during their growth phase inhibited
      MNC formation in the presence of granulocyte-macrophage colony-stimulating factor
      (GM-CSF) and 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. Diluted CM (1:81) from
      differentiated cells obtained after cultivation for more than 20 days stimulated
      MNC formation, but at lower dilutions inhibited their formation. Dialyzed CM
      (greater than 2000 mol wt) from the differentiated cells was more stimulatory
      than undialyzed CM and showed no inhibitory effect on MNC formation. The
      inhibitory effect was observed with filtered (less than 3000 mol wt) CMs and was
      specific for osteoblastic cell CM. Prostaglandin E2 (PGE2) was detected in the CM
      from undifferentiated or differentiated MC3T3-E1 cells at concentrations (317 +/-
      66 and 1287 +/- 179 pg/ml, respectively) sufficient to inhibit MNC formation, and
      this inhibition was partially abolished with CM (at 3-fold dilution) in
      indomethacin-treated cells (PGE2, less than 20 pg/ml), suggesting PGE2-mediated
      inhibition of MNC formation and the presence of another factor(s) besides PGE2
      that influenced MNC formation. In contrast to day 3 CM plus 1,25-(OH)2D3, day 60
      CM plus 1,25-(OH)2D3 induced MNC formation even in the absence of GM-CSF, and
      this induction was inhibited by an antibody to GM-CSF. Secondary colony formation
      assays showed the presence of a GM-CSF-like factor in the day 60 CM. These
      findings indicate that osteoblastic cells are involved in the process of
      osteoclastic cell formation, with at least two soluble factors produced by
      osteoblasts, a GM-CSF-like factor, which is stimulatory, and PGE2, which is
      inhibitory. The effects of CMs also differed depending on the stage of osteoblast
      differentiation.

PMID- 1999178
TI  - Cyclosporin-A in vitro decreases bone resorption, osteoclast formation, and the
      fusion of cells of the monocyte-macrophage lineage.
AB  - We studied the in vitro effect of cyclosporin-A (CyA) on bone resorption using a
      fetal rat long bone-resorbing assay. CyA inhibited both PTH-stimulated and
      unstimulated bone resorption. The inhibitory effect of CyA on basal resorption
      was dose dependent, and it was more pronounced during the second period (less
      than or equal to 0.1 microgram/ml) of culture (days 5-7) than during the first
      period (days 2-4). A cytotoxic effect was ruled out by the absence of decrease in
      [3H]thymidine incorporation into bones up to a concentration of 5 micrograms/ml
      CyA. Histomorphometry performed after 4 and 7 days of culture showed that CyA (1
      microgram/ml) decreased the number of osteoclasts per bone section after 7 days
      of culture (23.5 +/- 4.0 vs. 41.7 +/- 2.9 osteoclasts/bone section; P less than
      0.05), but not after 4 days (25.6 +/- 3.3 vs. 23.0 +/- 2.5). These data suggested
      an effect of CyA on osteoclastic differentiation rather than on the function of
      mature osteoclasts. We further assessed the mechanisms of the inhibitory effect
      of CyA on osteoclastic differentiation in order to determine 1) the level of this
      action (proliferation and/or fusion of osteoclast precursors), and 2) if this
      action is direct or indirect. Autoradiographic studies were performed on bone
      sections after incubation of bones with [3H]thymidine for the last 48 h of
      culture. CyA decreased slightly but significantly the percentage of labeled
      nuclei per osteoclast and the number of osteoclasts containing at least one
      labeled nucleus (20.2 +/- 0.7 vs. 33.2 +/- 3.5; P less than 0.02). Moreover the
      number of nuclei per osteoclast was decreased after 7 days in CyA-treated bones
      (2.4 +/- 0.05 vs. 3.0 +/- 0.1; P less than 0.02). Taken together these results
      demonstrate that CyA slightly decreased the proliferation of osteoclast
      precursors, but markedly decreased their fusion. Similar effects were observed in
      cultures of rat marrow macrophages. CyA (1 microgram/ml) inhibited the fusion of
      macrophages into multinucleated cells elicited by 1 nM 1,25-dihydroxyvitamin D3,
      but had only a slight effect on the proliferation of these cells, as assessed by
      autoradiography. CyA also inhibited the formation of multinucleated cells and the
      fusion index in long term cultures of human cord blood monocytes, a cellular
      model for osteoclastic differentiation. By contrast, CyA had no effect on the
      formation of myotubes by fusion of cultured mononucleated rat myoblasts.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 1999179
TI  - Defective tolerance to the toxic and metabolic effects of interleukin 1.
AB  - The effect on food intake, body weight, and survival of mice given recombinant
      lipopolysaccharide (LPS), tumor necrosis factor/cachectin (TNF), or interleukin 1
      (IL-1) (5 micrograms/mouse, ip, twice daily) was studied. All agents induced a
      rapid reduction of food intake and body weight after 1 day of treatment. Unlike
      TNF and LPS, IL-1 given as two daily administrations of 5 micrograms was lethal
      within 3 days. Mice treated with LPS or TNF rapidly developed tolerance to their
      anorectic effect, whereas tolerance to IL-1 required a longer time to develop and
      was not complete. We investigated the possible roles of changes in serum
      corticosterone and glucose in the effects of LPS, TNF and IL-1. A single
      injection of LPS, TNF, or IL-1 markedly increased serum corticosterone levels
      after 2 h. After only 2 days of chronic treatment, mice given LPS or TNF were
      refractory to induction of serum corticosterone by a subsequent injection of LPS
      or TNF, but mice given IL-1 for 2 days were still fully responsive to IL-1. IL-1,
      unlike TNF and LPS, induced a marked hypoglycemic response. Repeated
      administration of IL-1 sensitized to its hypoglycemic effect. This lack of
      adaptation to the increase of serum corticosterone and hypoglycemia was also
      observed when IL-1 was given at lower, nonlethal doses (0.25-1.0 microgram) and
      for a longer period (up to 8 days). The defective tolerance to the metabolic and
      toxic effects of IL-1 in this experimental model indicates that there are major
      differences between the in vivo biological responses to IL-1 and TNF.

PMID- 1999180
TI  - Neurons that migrate from the olfactory epithelium in the chick express
      luteinizing hormone-releasing hormone.
AB  - In several mammalian species, luteinizing hormone-releasing hormone (LHRH)
      neurons have been shown to migrate from nasal regions to the brain during early
      development. Using immunocytochemistry, we have identified LHRH containing
      neurons in developing chick embryos. In embryonic day 4 (E4) and E5 animals, a
      small group of LHRH immunoreactive (IR) neurons were found just ventral to the
      olfactory pit. LHRH-IR neurons were also found within the immunoreactive (IR)
      neurons were found just ventral to the olfactory pit. LHRH-IR neurons were also
      found within the nasal epithelium. In E6 and E7 animals, many more LHRH-IR
      neurons were observed in nasal epithelium, in close association with the
      olfactory nerve, and within the telencephalon. These data are consistent with the
      hypothesis that LHRH neurons in chicks originate within nasal structures and
      migrate into the brain.

PMID- 1999181
TI  - Presence of luteinizing hormone-releasing hormone (LHRH) mRNA in rat spleen
      lymphocytes.
AB  - Pursuant to our report of an immunoreactive and bioactive luteinizing hormone
      releasing hormone (LHRH)-like molecule in rat spleen lymphocytes, we sought to
      determine whether these cells were capable of synthesizing LHRH by determining
      whether lymphocytes contain LHRH mRNA. To do this, total RNA was extracted from
      hypothalamic tissue, anterior pituitaries and from lymphocytes, and then this was
      reverse transcribed to cDNA and amplified via the polymerase chain reaction (PCR)
      utilizing synthetic oligonucleotides bracketing a portion of the LHRH gene.
      Following gel electrophoresis a discrete band of the expected size of 375 base
      pairs was found in the hypothalamus (positive control), and in lymphocytes, but
      not in the anterior pituitary (negative control). Furthermore, after Southern
      blotting, a 32P-labelled LHRH cDNA, hybridized to the 375 base pair, was
      amplified in hypothalamus fragments and in lymphocytes, but not in anterior
      pituitary tissue. These data strongly suggest that LHRH, in addition to being an
      important neuropeptide, is an immune cell synthesized immunomodulator.

PMID- 1999182
TI  - Regulation of the expression of the sex-specific isoforms of cytochrome P-450 in
      rat liver.
AB  - The hepatic metabolism of steroid hormones and of xenobiotics frequently depends
      on the expression of the sex-specific isoforms of cytochrome P-450 and on
      differences in sex hormones. Following biochemical, immunological and molecular
      biological investigations, it was shown that in adult rat liver there exist at
      least four male-specific and one female-specific isoforms of cytochrome P-450.
      The designation of these sex-specific genes is IIC11, IIIA2, IIC13 and IIA2 in
      males, and IIC12 in females. The irreversible programming of the expression of
      these isoforms of cytochrome P-450 in adulthood occurs during the perinatal
      period of life, and is named enzyme imprinting. One of the main factors that
      regulates the expression of the sex-specific isoforms of cytochrome P-450 is the
      level of androgens in the blood. Castration of adult rats decreased the level of
      the male isoforms of cytochrome P-450 and the activity of the monooxygenase
      enzyme system that remained higher than in intact females. The mechanism of
      enzyme imprinting can be explained as follows: neonatal androgens program the
      secretion of hypothalamic hormones, somatostatin and growth-hormone-releasing
      factor. These factors determine the type of growth hormone secretion in adult
      rats, and this controls the type of sex-specific isoforms of cytochrome P-450
      expressed in adulthood. Metabolic regulation similar to that outlined above was
      shown to occur for several metabolism-dependent chemical carcinogens. Such a
      pathway may explain the different sensitivity displayed by male and female rats
      to treatment with these carcinogenic agents. One possible way of modulating the
      expression of some isoforms of cytochrome P-450 in adult rats is by treating
      neonates with specific xenobiotics that change the constitutive expression of
      neonatal androgens. It appears that this enzyme imprinting plays an important
      role in determining the individual sensitivity to the carcinogenic effects of
      chemicals.

PMID- 1999184
TI  - Secondary structure of the 5' external transcribed spacer of vertebrate pre-rRNA.
      Presence of phylogenetically conserved features.
AB  - Eucaryotic pre-rRNA spacers are evolutionarily highly variable in sequence and
      size, and are markedly expanded in vertebrates, particularly in mammals. The
      longest mammalian spacer by far is the 3.5-4-kb 5' external transcribed spacer
      (5'-ETS), which is excised in two steps. We present a folding model for the
      entire mammalian 5'-ETS, derived from comparative analyses and thermodynamic
      predictions for mouse, rat and human sequences, which should prove helpful in
      identifying cis-acting processing signals, particularly those involved in its
      early internal cleavage, for which U3 RNA is an essential factor. Although the
      rodent and primate sequences have extensively diverged, a series of relatively
      conserved sequence tracts can nevertheless be identified: they participate in
      base-pairing, preserved through the occurrence of compensatory base changes,
      which delineate four independent domains of secondary structure. The first domain
      is located entirely upstream from the site of internal cleavage. The second
      domain, immediately downstream from this cleavage site, encompasses most of the
      region required for faithful and efficient in vitro processing at this site.
      Phylogenetically supported conserved structures also define two other independent
      domains, encompassing most of the 5'-ETS length, with the presence of giant
      hairpins (extending from the conserved core elements) which exhibit both some
      analogous features and substantial differences between man and mouse. The
      comparative analysis was extended to the two other vertebrate sequences available
      so far, amphibians Xenopus laevis and Xenopus borealis. The amphibian folding
      model, supported by comparative evidence between these two species, displays some
      features in common with the mammalian model, with a similar organization into
      four separate domains of secondary structure, suggesting the functional relevance
      of these structures in the process of ribosome formation.

PMID- 1999183
TI  - Genomic organization of the human procollagen alpha 1(II) collagen gene.
AB  - The nucleotide sequence of the human procollagen alpha 1(II) collagen gene
      extending from within the first intron through exon 15, and part of the 15th
      intron has been determined. This sequence analysis (7056 bases) identifies the
      intron/exon organization of the region of this gene encoding the N-propeptide and
      part of the triple-helical domain. Structural comparison of this with the genes
      of other human fibrillar collagens shows considerable diversity in terms of size
      and number of introns and exons that encodes the N-propeptide domain. Although
      the genomic structure of the human procollagen alpha 1(II) gene is quite
      different from the rat procollagen alpha 1(II) gene, the nucleotide coding
      sequences are 89% identical.

PMID- 1999185
TI  - Cuttlefish sperm protamines. 1. Amino acid sequences of two distinct variants.
AB  - The amino acid sequences of two cuttlefish protamine variants Sp1 and Sp2 have
      been established from automated sequence analysis and mass spectrometry data. Sp1
      (57 residues) and Sp2 (56 residues) have molecular masses of 8410 and 8253 Da,
      respectively. They are almost identical proteins which differ only by one residue
      of arginine and the position of two of the serine residues (14 and 37 in Sp1; 13
      and 35 in Sp2). With an arginine content of about 77%, cuttlefish protamine is
      one of the most basic proteins which have ever been characterized and the first
      typical protamine sequenced in invertebrates. It is closely similar to sperm
      basic proteins identified in squids but strongly differs from the protamine-like
      components isolated from the sperm of bivalve molluscs.

PMID- 1999186
TI  - Cuttlefish sperm protamines. 2. Mass spectrometry of protamines and related
      peptides.
AB  - The sequence of very basic proteins such as protamines (more than 50% arginines)
      and related peptides has been determined using mass spectrometry in conjunction
      with Edman degradation. The capabilities of three mass spectrometric (MS)
      techniques [fast-atom-bombardment (FAB), 252Cf plasma desorption (252CFPD) and
      electrospray (ES)] have been evaluated on stallion protamine 1, cuttlefish
      protamine, and the corresponding cleavage peptides. In contrast to FAB-MS and
      252Cf PD-MS, ES-MS made possible an easy determination of the molecular mass of
      the intact protamines (approximately 8 kDa). With ES-MS about 0.2 nmol was
      sufficient to yield a mass measurement with an accuracy of 0.05%. On peptides
      smaller than 3500 Da, both FAB-MS and 252Cf PD-MS allowed mass measurements with
      an accuracy of 0.1%. 252Cf PD-MS appeared more sensitive than FAB-MS by about a
      factor of 10. FAB-MS is nevertheless particularly interesting since in most cases
      it produced spectra with intense A-type fragmentation ions which provided
      reliable primary structure information.

PMID- 1999187
TI  - Tryptophan phosphorescence of G-actin and F-actin.
AB  - The tryptophan phosphorescence spectrum, intensity and decay kinetics of G-actin
      and F-actin were measured over a temperature range of 140-293 K. The fine
      structure in the phosphorescence spectra at low temperature, with O,O vibrational
      bands centered at 405 nm and 415.5 nm for both species, reveals a marked
      heterogeneity of the chromophore environment. The thermal quenching profile
      distinguishes these sites in terms of their flexibility, and shows that probably
      only one of the four tryptophan residues is still phosphorescent at ambient
      temperature due to its location in a relatively rigid buried core. Although some
      differences are demonstrated between G-actin and F-actin at low temperature, the
      identity of the triplet lifetime at ambient temperature strongly supports the
      notion that the conformation of the macromolecule is largely unaffected by
      polymerization. Preliminary phosphorescence anisotropy measurements demonstrate
      both the occurrence of singlet-singlet energy transfer among tryptophan residues
      and a strong immobilization of actin in the polymerized state.

PMID- 1999189
TI  - Why do many Michaelian enzymes exhibit an equilibrium constant close to unity for
      the interconversion of enzyme-bound substrate and product?
AB  - 1. The idea is advanced that an evolutionary pressure in the direction of
      increased metabolic fluxes should lead to the selection at any evolutionary stage
      of enzymes which are optimally efficient considering the total evolutionary
      effort which has been spent on their improvement as catalysts. Relationships are
      derived which may be used for determination of the optimal state of operation of
      a Michaelian enzyme at a given total evolutionary effort as measured, for
      instance, by the mean magnitude of variable rate constants in the reaction
      mechanism. These relationships are applied to characterize the dependence on the
      total evolutionary effort of the optimal value of the equilibrium constant (Kint)
      for the conversion of enzyme-bound substrate into enzyme-bound product. 2. The
      results show that the optimal value of Kint reflects primarily the magnitude of
      the overall equilibrium constant for the catalysed reaction, whether or not the
      enzyme operates close to equilibrium. When the total evolutionary effort tends
      towards infinitely high values, Kint approaches unity, regardless of the
      magnitude of the overall equilibrium constant and of the concentrations of
      substrate and product. Concomitantly, the enzyme approaches its ultimate state of
      catalytic perfection where all variable rate constants in the mechanism tend
      towards infinitely high values. 3. It is concluded from previously reported
      kinetic data that triosephosphate isomerase has been subjected to such a low
      total evolutionary effort that the enzyme cannot possibly have reached (or even
      significantly approached) the ultimate state of perfection where the Kint value
      necessarily becomes close to unity. The reason why this enzyme exhibits a Kint
      value relatively close to unity is that it catalyses a reaction with an
      equilibrium constant relatively close to unity. Evidence is presented to show
      that similar considerations may apply for other enzymes operating by the examined
      reaction mechanism. 4. Analytical data are reported which indicate that Kint
      ultimately approaches unity because forward and reverse rate constants for the
      interconversion of enzyme-bound substrate and product are equivalent with regard
      to the evolutionary effort required to increase their magnitude.

PMID- 1999188
TI  - Demonstration of a molybdenum- and vanadium-independent nitrogenase in a nifHDK
      deletion mutant of Rhodobacter capsulatus.
AB  - In Rhodobacter capsulatus there exists, in addition to a conventional Mo
      containing nitrogenase, a second, Mo-indendent nitrogenase which was demonstrated
      in wild-type cells as well as in cells of a nifHDK- mutant. To construct this R.
      capsulatus mutant, a 4-kb BglII-HindIII fragment encompassing nifK, nifD and most
      of the nifH coding region was substituted by an interposon coding for kanamycin
      resistance. The alternative nitrogenase is repressed by molybdenum. Mo
      concentration greater than 1 ppb in the growth medium prevented diazotrophic
      growth of nifHDK- cells and the expression of nitrogenase activity. The Mo
      independent nitrogenase was maximally derepressed in activated carbon-treated
      media which contained less than 0.05 ppb Mo, high concentrations of iron (1 mM
      ferric citrate) and serine as N source. Under N2-fixing and optimal Mo-deficient
      conditions, nifHDK- cells grew with a doubling time of 9 h. The highest activity
      achieved with whole cells was 1.2 nmol ethylene.min-1.mg protein-1. Vanadium
      neither stimulated nor inhibited growth and activity. The alternative nitrogenase
      reduced acetylene to both ethylene and ethane. With whole cells (nifHDK-) the
      proportion of ethane varied over 2-5% depending on the amount of residual traces
      of Mo in the medium. The addition of Mo to a growing, nitrogenase-active culture
      resulted in a slow decrease of total activity but also in a simultaneous increase
      of ethane production up to 40%. In contrast, cell-free extracts and the purified
      enzyme did not show any or only very little ethane formation (0-0.4%). Both
      enzyme components appeared to be very labile proteins. Component 2 lost almost
      all its activity during cell breakage. With component 1 in crude extracts, if
      complemented with the stable component 2 of the Mo-nitrogenase from Xanthobacter
      autotrophicus, a recovery of 50% of the original whole cell activity could be
      achieved. During purification, component 1 (from the nifHDK- mutant) remained
      remarkably stable. The partially purified component 1 had a pH optimum (acetylene
      reduction) of 7.8-8.0, relatively high affinity to acetylene (Km = 0.055 mM) and
      was analyzed to contain 20 mol Fe atoms/mol protein, 0.2 mol Mo atoms and
      negligible amounts of V, W and Re. The dithionite-reduced dinitrogenase appeared
      to be ESR-silent. The results indicate that the alternative nitrogenase of R.
      capsulatus is not a vanadium enzyme but rather a heterometal-free Fe-nitrogenase
      or a nitrogenase with an as-yet-unidentified heterometal atom.

PMID- 1999190
TI  - ADP is a substrate for the AAUAAA-directed poly(A) addition reaction catalyzed by
      HeLa cell nuclear extracts.
AB  - The specific poly(A) addition reaction catalyzed by crude nuclear extracts from
      HeLa cells can use ADP as efficiently as ATP as the donor of AMP residues. Both
      the ADP- and ATP-supported reactions require an intact upstream polyadenylation
      signal sequence element (AAUAAA). The mutated signal sequence (AACAAA) supports
      neither reaction. The ADP-supported poly(A) addition reaction can be resolved by
      glycerol gradient centrifugation of the crude nuclear extract into two components
      which are active when recombined but are inactive individually. The ATP-supported
      poly(A) addition is reconstituted by recombining the same gradient fractions, but
      the activity is lower than that supported by ADP, suggesting that an ATP-specific
      factor has been removed. A 150 mM KCl fraction DEAE-Sepharose of the nuclear
      extract, also devoid of the ATP-supported poly(A) addition reaction, retains a
      normal ADP-supported reaction. Together, these data show that ADP is a substrate
      for polyadenylation, and suggest that different factors might be required to
      induce ADP- or ATP-specificity in the poly(A) addition reaction.

PMID- 1999191
TI  - Synthesis of myristoyl-carba(dethia)-coenzyme A and S-(3-oxohexadecyl)-coenzyme
      A, two potent inhibitors of myristoyl-CoA:protein N-myristoyltransferase.
AB  - 1. Two non-hydrolysable analogues of myristoyl-coenzyme A were synthesised and
      spectroscopically characterized. Myristoyl-carba(dethia)coenzyme A was prepared
      in a multistep synthesis starting from tridecyl vinyl ketone. S-(3-Oxohexadecyl)
      coenzyme A was synthesised from 3-oxohexadecyl chloride by direct condensation
      with coenzyme A. 2. Both analogues were strong competitive inhibitors of N
      myristoyltransferase from yeast. Ki values of 0.3 and 0.25 microM were determined
      for myristoyl-carba(dethia)-coenzyme A and S-(3-oxohexadecyl)-coenzyme A,
      respectively.

PMID- 1999192
TI  - A tetranectin-related protein is produced and deposited in extracellular matrix
      by human embryonal fibroblasts.
AB  - Tetranectin is a tetrameric human plasma protein that binds to plasminogen
      kringle 4. Its amino acid sequence is homologous with the C-terminal parts of
      asialoglycoprotein receptors and proteoglycan core proteins. In the present
      study, we have demonstrated that the human embryonal fibroblast cell line WI-38
      produce a tetranectin-related molecule, which might, by several criteria, be
      similar to tetranectin from plasma. These criteria include immunoblotting
      analysis of conditioned cell medium revealing a protein band with Mr 17,000,
      indistinguishable from the Mr of plasma tetranectin. A preparation obtained by
      purification of conditioned medium by affinity chromatography on an anti-(plasma
      tetranectin) IgG column also contained the Mr 17,000 protein. This protein
      (partly purified from the conditioned medium) was shown by crossed
      immunoelectrophoresis to bind to heparin, CaCl2 and plasminogen kringle 4, as
      previously described for tetranectin in plasma. Importantly, this tetranectin
      related protein is not only present in conditioned culture medium, but the Mr
      17,000 protein reacting with anti-(plasma tetranectin) IgG was also present in
      the extracellular material, remaining after removal of WI-38 cells from the
      culture dishes, as demonstrated by immunoblotting analysis and immunocytochemical
      staining. We conclude that WI-38 cells produce a tetranectin-related protein and
      secrete it into the extracellular matrix.

PMID- 1999194
TI  - Dependence of lysozyme-catalysed solubilization of Proteus mirabilis
      peptidoglycan on the extent of O-acetylation.
AB  - The degree of peptidoglycan O-acetylation in 14 strains of Proteus mirabilis has
      been accurately determined by a procedure which employs the quantitation of mild
      base-released acetic acid by HPLC, and the estimation of peptidoglycan
      concentration by cation-exchange amino acid analysis. The beta-D-N,6-O
      diacetylmuramyl content of all isolated and purified peptidoglycans was ranged 20
      52.8%, relative to the total muramic acid concentration. Each of the O-acetylated
      peptidoglycans was found to be resistant to solubilization by both human and hen
      egg-white lysozymes and for hen egg-white lysozyme, the extent of this resistance
      was dependent upon the degree of O-acetylation. The steady-state parameters, Km
      and V, for the hen-egg-white-lysozyme-catalysed solubilization of various
      peptidoglycan preparations were determined at pH 6.61 and 25 degrees C. Values of
      Km for the different peptidoglycan samples were found to increase with increasing
      O-acetylation, whereas with V no such relationship appeared to exist. An increase
      in the overall change in the standard Gibbs free energy of activation
      [delta(delta G#)], a consequence of increasing O-acetylation, was observed, and
      is shown to result from the weaker affinity of the enzyme for the modified
      substrates.

PMID- 1999193
TI  - Covalent binding of dolichyl phosphate to proteins in rat liver.
AB  - Rats were injected via the portal vein with (RS)-[5-3H]-mevalonolactone and the
      lipids were extracted. From fractions of liver homogenate, all labeled dolichol,
      cholesterol and ubiquinone could be extracted, but about 40% of microsomal and
      lysosomal dolichyl phosphate was only released after alkaline hydrolysis. Only a
      small amount of the non-extractable radioactivity was found to be associated with
      alpha-unsaturated polyprenyl phosphate. There was no difference in the
      polyisoprenoid pattern when the two pools of dolichyl phosphate were compared. On
      the other hand, the specific activity of the bound lipid was only half that of
      the extractable form. After phenyl-Sepharose chromatography, a peak of protein
      was isolated exhibiting a 25-fold enrichment in bound radioactive dolichyl
      phosphate. Treatment with a non-specific protease, followed by chromatography,
      gave polypeptide fragments associated with bound lipids. On SDS/PAGE a major
      protein band at 23 kDa and some minor bands with higher molecular masses were
      found to be associated with this lipid. The results indicate the presence of
      covalently bound dolichyl phosphate in rat liver.

PMID- 1999195
TI  - An additional promoter functions in the human aldolase A gene, but not in rat.
AB  - The aldolase A gene was isolated from a human DNA library, mapped and sequenced.
      This gene comprises 12 exons and spans 6.5 kb. From the genomic DNA sequence and
      from the previous sequence analysis of the cDNA, it was revealed that the first
      exon L1 and the second exon encode the 5' non-coding sequence of mRNA L1, while
      the third and forth exons (corresponding to exons M and L2) encode different
      mRNA, mRNA M and L2, respectively; the following eight exons (exons 5-12) are
      shared commonly by all the mRNA species. These results indicate that the mRNA
      species are generated from a single aldolase A gene from one of exons L1, M or
      L2, in addition to exons 5-12, and also that the usage of a leader exon is
      similar but clearly distinct from that of rat aldolase A gene which we analyzed
      [Joh, K., Arai, Y., Mukai, T. & Hori, K. (1986) J. Mol. Biol. 190, 401-410]. By
      comparing the promoter regions in the human and rat aldolase A genes, we found
      similar sequences in the rat genome corresponding to those of the human L1, M and
      L2 promoter. We could not, however, detect any transcripts starting from
      sequences corresponding to the human L1 promoter in the rat genome, although the
      products corresponding to human M and L2 were detected. Thus, we conclude that
      the L1 promoter was either acquired by the human genome or deleted from the rat
      genome after human and rat diverged during evolution.

PMID- 1999196
TI  - Blocking of the receptor-mediated invasion of erythrocytes by Plasmodium knowlesi
      malaria with sulfated polysaccharides and glycosaminoglycans.
AB  - Invasion of human erythrocytes by Plasmodium knowlesi requires the Duffy blood
      group antigen. P. knowlesi merozoites synthesize a 135-kDa polypeptide which
      binds to the Duffy antigen with receptor-like specificity. In this study, we show
      that the sulfated polysaccharide fucoidan and the glycosaminoglycan dextran
      sulfate inhibit the binding of the 135-kDa polypeptide to human Duffy-positive
      and rhesus erythrocytes while the chondroitin sulfates do not. Fucoidan and
      dextran sulphate also blocked the in vitro invasion of human Duffy b and rhesus
      erythrocytes cells by P. knowlesi merozoites. These inhibitors were more
      effective at blocking the binding of the 135-kDa polypeptide to human Duffy b
      erythrocytes than to rhesus erythrocytes, which correlated with them having a
      greater inhibitory effect on invasion of merozoites into human than into rhesus
      erythrocytes. The blocking by these sulfated sugars is not related to charge
      density on the polysaccharides; fucoidan with a relatively low charge density
      blocks binding of the 135-kDa polypeptide at 4 micrograms/ml, while the highly
      negatively charged chondroitin sulfates do not block binding even at the
      concentration of 1 mg/ml. Furthermore, fucoidan-Sepharose bound and removed the
      135-kDa polypeptide from parasite culture supernatants with a selectivity equal
      to that of the Duffy blood group antigen. The negatively charged sulfate groups
      on fucoidan and dextran sulfate and the conformation in which they are held
      possibly mimic similarly charged groups on the Duffy antigen which bind the 135
      kDa P. knowlesi polypeptide.

PMID- 1999197
TI  - Characterization of the cell-cycle-regulated protein calcyclin from Ehrlich
      ascites tumor cells. Identification of two binding proteins obtained by Ca2(+)
      dependent affinity chromatography.
AB  - The nearly complete amino acid sequence obtained for murine calcyclin from
      Ehrlich ascites tumor cells reveals a very strong similarity with the rat and
      human sequences previously deduced from corresponding cDNA clones. While mouse
      and rat calcyclins are identical, the human protein shows at three positions a
      conservative amino acid replacement. Using a mouse calcyclin affinity matrix, two
      proteins with molecular masses of about 36 kDa have been purified from Ehrlich
      ascites tumor cells. The interaction between these two proteins and the
      immobilized calcyclin is strictly Ca2(+)-dependent. Immunological criteria and
      partial sequence data identify the two calcyclin-binding proteins as the
      phospholipid-binding protein annexin II (p36) and the glycolytic enzyme
      glyceraldehyde-3-phosphate dehydrogenase. These observations suggest that
      calcyclin may exert its physiological function by a Ca2(+)-dependent interaction
      with cellular targets, e.g. annexin II or glyceraldehyde-3-phosphate
      dehydrogenase.

PMID- 1999198
TI  - Characterization of the cellular binding domain and the effects of monoclonal
      antibodies and thrombin inhibitors on the binding and internalization of the
      antithrombin-III--thrombin complex by cultured cells.
AB  - Antithrombin III (AT) binds to cultured cells mainly as a complex with thrombin
      or other serine proteases rather than in its free form. This implies that, upon
      complex formation, a new determinant appears on the AT molecule which is
      recognized by the cells. Fragmentation of AT by cyanogen bromide exposes this
      determinant and an 8-kDa fragment is recognized by cultured cells. The binding of
      this fragment to cultured cells is inhibited by antithrombin-III-thrombin (AT-T)
      complex, but not by free AT. The putative cellular binding domain of AT-T is
      located over amino acid residues 253-314 of AT, in the large loop close to the
      carboxy-terminus of the molecule. The cell-associated AT-T is internalized and
      degraded, forming the thrombin-modified AT (ATM). This process is inhibited by
      lysosomal degradation inhibitors, such as chloroquine or benzamidine. Thus, the
      appearance of ATM in cells is not a result of its binding to the cell surface,
      but probably a result of lysosomal degradation of cell-associated AT-T. Another
      degradation product, with a molecular mass of 43 kDa, appears in cells along with
      the appearance of ATM. Hirudin, a specific inhibitor of thrombin, inhibits the
      cellular internalization of AT-T complexes, indicating a possible role for
      thrombin activity in the internalization process of complexes. Monoclonal
      antibodies (mAb) against AT, whose epitopes on the AT molecule have been located,
      affect the binding of AT-T to cultured cells. Two mAb, A10 whose epitope is found
      outside of the cellular binding site, and B108 whose epitope may overlap this
      sequence, totally inhibit the binding of the complex to cells. Inhibition of
      binding results either from steric hindrance or induced changes in the binding
      site.

PMID- 1999199
TI  - Three-dimensional correlated NMR study of Megasphaera elsdenii flavodoxin in the
      oxidized state.
AB  - The value of a three-dimensional (3D) non-selective total correlation/nuclear
      Overhauser enhancement spectroscopy (TOCSY-NOESY) spectrum for making sequential
      resonance assignments in proteins is demonstrated using the relatively large
      Megasphaera elsdenii flavodoxin (molecular mass 15 kDa) in the oxidized state. An
      easy and concise method for the analysis of 3D-NMR spectra and a strategy for the
      resonance assignment of 3D-NMR protein spectra is introduced. In this context,
      non-selective TOCSY-NOESY is compared with selective TOCSY-NOESY and non
      selective NOESY-TOCSY. Sequential assignments in various secondary structure
      elements of flavodoxin are made using the method of analysis introduced. NOEs not
      previously identified in 2D-NMR spectra due to resonance overlap are found in the
      3D Clean-TOCSY-NOESY spectrum. Also additional side-chain assignments could be
      made.

PMID- 1999200
TI  - An acyl-carrier-protein-thioesterase domain from the 6-deoxyerythronolide B
      synthase of Saccharopolyspora erythraea. High-level production, purification and
      characterisation in Escherichia coli.
AB  - The C-terminal region of a multifunctional polypeptide from the 6
      deoxyerythronolide B synthase of Saccharopolyspora erythraea is predicted to
      contain an acyl carrier protein and a thioesterase or acyltransferase activity
      [Cortes, J., Haydock, S. F., Roberts, G. A., Bevitt, D. J. & Leadlay, P. F.
      (1990) Nature 348, 176-178]. Site-directed mutagenesis by means of the polymerase
      chain reaction was used to construct an efficient pT7-based expression plasmid
      for this domain. The recently developed technique of electrospray mass
      spectrometry was used to demonstrate that the purified protein had not been post
      translationally modified by attachment of a 4'-phosphopantetheine group. However,
      treatment with the serine proteinase inhibitor phenylmethylsulphonyl fluoride led
      to highly selective labelling of the predicted active site of the thioesterase or
      acyltransferase.

PMID- 1999201
TI  - Transcription of synthetic DNA containing sequences with dyad symmetry by wheat
      germ RNA polymerase II. Increased rates of product release in single-step
      addition reactions.
AB  - Interaction of purified eukaryotic RNA polymerase II with various synthetic
      palindromic DNA sequences is associated with the formation of transcriptional
      complexes of different stabilities, i.e. having different propensities for
      releasing the nascent transcript. This phenomenon was observed by using wheat
      germ RNA polymerase II and a series of double-stranded template polymers
      containing palindromic repeating motifs of 6-16 bp, with regulatory alternating
      purine and pyrimidine bases such as d[ATA(CG)nC].d[TAT(GC)nG], with n = 1, 3 or 6
      referred to as d(GC), d(GC)3 or d(GC)6, respectively. We also synthesized two
      double-stranded methylated polymers, containing the repeating units
      d(ATAm5CGm5C).d(TATGm5CG) and d[ATA(m5CG)6m5C].d[TAT(Gm5C)6G] [designated d(GmC)
      and d(GmC)6, respectively]. All of these polymers served as templates for the
      reaction of single-step addition of CTP to a CpG primer catalysed by wheat-germ
      RNA polymerase II, to an extent that seems well correlated with the number of
      potential initiation sites within the DNA molecules. Furthermore, in these
      reactions, the enzyme appears to form relatively stable transcriptional
      complexes, as trinucleotide product was released only very slowly. In marked
      contrast to the results with the CpG primer, the single-step addition reaction
      primed by UpA, i.e. the synthesis of UpApU proceeded at a much higher velocity
      and was strongly enhanced by increasing the d(G-C) content of the repeating units
      of the DNA polymers. Thus, taking into account the number of potential sites at
      which UpApU synthesis could occur, the extent of UpApU synthesis was increased
      about 12-fold with d(GC)6 compared to that with the d(GC) template. The catalytic
      nature of the reaction necessarily implies that the stability of the
      transcription complexes with the plant RNA polymerase II decreased as the d(G-C)
      content of the repeating motif increased. Furthermore, although the synthesis of
      CpGpC could be demonstrated with d(GmC)6 as template, the UpA-primed synthesis of
      UpApU could not be detected with this polymer. The results obtained in
      transcription of these polymers are discussed in relation to the potential
      involvement of palindromic DNA in transcription termination and attenuation in
      the presence of RNA polymerase II.

PMID- 1999202
TI  - Percutaneous transgastric internal drainage, endoscopy and stenting of the
      pancreatic duct; a new technique.

PMID- 1999203
TI  - An alternative method of three-dimensional reconstruction from two-dimensional CT
      and MR data sets.
AB  - Cross-sectional images for medical diagnosis and therapy are obtained by
      sonography, CT or MRI. We propose an alternative solution to the problem of
      constructing a set of cross-sectional contours from two-dimensional (2D) CT or MR
      data sets. The method reduces the problem of constructing a shape over the cross
      sections to one of constructing a sequence of partial shapes, each of them
      connecting two cross-sections lying on adjacent planes. The solution makes use of
      a spatial mathematical formalism (Delaunay triangulation). MR investigations were
      carried out on different objects (hips, livers) to illustrate the two-dimensional
      MR data sets by the reconstruction method. The resulting images represent the
      original image data in a way that is more suitable for observation of 3D
      relationships than the conventional cross-sectional viewing model.

PMID- 1999204
TI  - User discipline in a personal computer-based filing of ultrasound records.
AB  - The discipline of entering ultrasound examination data in a personal computer
      file was studied over two periods. During the first period (19 weeks), the use of
      the computer was limited to one laboratory. During the second period (14 weeks),
      the computer was shared by three laboratories operating in nearby premises.
      During the study, 2857 (89%) of a total of 3209 ultrasound examinations performed
      were duly recorded in the data file. The frequency of failure to enter data was
      markedly higher during the second period (7-45%) than during the first period
      (5%) of the study. Overall, there was a highly significant (p less than 0.001)
      tendency to enter pathological findings at the expense of normal and non
      diagnostic findings. The ease of access to the computer and the number of
      examinations recorded appear to determine user conscientiousness in filing data.
      Selection and omission of data impair the usefulness of the data log in research.

PMID- 1999205
TI  - Role of radionuclide ventriculography in evaluating cardiac function.
AB  - The role of nuclear cardiology techniques for evaluating cardiac function has
      become increasingly important among other diagnostic techniques. The current
      status of radionuclide imaging of left and right ventricular function allows
      accurate diagnosis of cardiac patients with both coronary and noncoronary
      disease. The combination of gated first-pass and equilibrium radionuclide
      ventriculography makes it possible to assess more completely cardiac function
      than by either technique alone. Of particular interest to most imaging physicians
      is the current position of exercise ventriculography in the diagnostic setting,
      especially since this test has undergone new scrutiny in its application to
      broader patient segments. This technique and issues related to its place in the
      diagnostic environment are discussed in this review article, with emphasis on
      relevance to the clinical laboratory.

PMID- 1999206
TI  - Technetium-99m nanocolloid for the scintigraphic assessment of inflammatory bowel
      disease in the colon: its value in comparison with indium-111-labelled
      granulocytes.
AB  - The usefulness of 99mTc-nanocolloid for the assessment of localization and
      disease activity of colitis in patients suffering from inflammatory bowel disease
      (IBD) was investigated in 10 patients. Results of 99mTc-nanocolloid scintigraphy
      were compared with Indium-111 autologous granulocyte scintigraphy and the
      activity index according to Van Hees. In none of the patients a true positive
      result of the 99mTc-nanocolloid scintigraphy was encountered, while 111In
      granulocyte scintigraphy was positive in 7 of 10 patients with active disease.
      Radioactivity became visible in the small bowel starting 2 h after injection of
      99mTc-nanocolloid most likely because of excretion by the liver of degradation
      products of the radiopharmaceutical. The authors conclude that despite a previous
      communication 99mTc-nanocolloid cannot replace 111In-granulocytes for the
      assessment of IBD patients with active colitis.

PMID- 1999208
TI  - Magnetic resonance imaging of peritoneal pseudocyst associated with Crohn's
      disease: a case report.

PMID- 1999207
TI  - Over-utilisation of radiography in the assessment of stapled colonic anastomoses.
AB  - We have reviewed the radiological studies in 31 patients who underwent stapled
      colorectal anastomoses using the EEA staple gun. In 10 patients there was
      clinical evidence to suggest anastomotic dehiscence. Nine of these patients had a
      disrupted staple ring on plain abdominal radiograph. In these days of audit and
      financial constraint, we suggest that radiological investigation should be
      reversed for those patients with questionable clinical evidence of an anastomotic
      leak.

PMID- 1999209
TI  - Percutaneous vascular foreign body retrieval: experience of an 11-year period.
AB  - Over an 11-year period, percutaneous retrieval of intravascular foreign bodies
      was performed in 12 patients, using urological forceps and retrieval baskets. No
      clinically significant complication occurred, success rate was 100%. Review of
      176 cases from the literature showed a success rate of 90%.

PMID- 1999210
TI  - Ultrasound and computed tomographic findings in pancreatic metastases.
AB  - This is a retrospective study of a series of seven patients with pancreatic
      metastases studied by ultrasonography and computed tomography. They were detected
      during tumor staging, or in the follow-up period of over 10 years of patients
      with advanced known malignancy. Lesions were multiple in two patients and
      solitary in five; solid in six cases and cystic in one. Clinically, four cases
      were asymptomatic and three cases presented with jaundice or epigastric pain.
      Ultrasonography and computed tomography findings were non-specific. Consequently
      it was not possible to differentiate solitary metastases from primary solid
      adenocarcinoma and cystadenocarcinoma of the pancreas. In these cases, computed
      tomography- or ultrasonography-guided biopsies had to be performed to obtain
      histological proof. However, multiple lesions discovered in a patient with a
      known malignancy can be assumed to be due to metastases.

PMID- 1999211
TI  - Sonographic manifestation of an inflamed Meckel's diverticulum: a case report.

PMID- 1999212
TI  - CT myelography in communicating syringomyelia.
AB  - Although the etiology of syringomyelia is not clearly understood, many surgical
      methods have been proposed for its treatment. One widely used technique in cases
      of communicating syringomyelia is that of posterior fossa decompression and
      plugging of the obex (Gardner's Operation). In this paper we present five cases
      of syringomyelia which were investigated using detailed myelo-computerized
      tomographic techniques, of which two appeared to be communicating syringomyelia
      and which were treated by posterior fossa decompression and obex plugging. We
      also discuss the place of computed tomography in the differential diagnosis of
      communicating syringomyelia.

PMID- 1999213
TI  - The MR evaluation of pachygyria and associated syndromes.
AB  - A retrospective study of 40 children with some form of pachygyria was performed
      at the Children's Memorial Hospital in Chicago. All 40 children had MR brain
      scans. We analyzed the MR findings, and correlated these findings with the
      clinical symptoms and course in all the children. We have autopsy findings in 15%
      these children. Based on our clinical, MR and autopsy findings, in conjunction
      with the medical literature, we found the following: (1) Pachygyria can occur as
      an isolated entity without an association with lissencephaly. The MR findings in
      these children consisted of a brain that demonstrated normal opercularization
      with either focal or diffuse areas of pachygyria without areas of agyria. These
      children live longer and have less severity of symptoms than the children with
      lissencephaly. (2) The MR findings in children with lissencephaly consisted of a
      brain that demonstrated abnormal opercularization with areas of total agyria or
      areas of agyria with pachygyria. (3) The MR findings in 25% of our children with
      polymicrogyria simulated pachygyria. The MR findings of the brain in these
      children consisted of a 'nubby' appearance to the outer surface of these abnormal
      gyri which resembled pachygyria but on histologic exam was polymicrogyria.

PMID- 1999214
TI  - MRI of bilateral seminal vesicle abscesses.

PMID- 1999215
TI  - Influence of radiographic contrast media on granulocyte enzymes and complement
      during uncomplicated urographies.
AB  - Four different radiographic contrast media (RCM) were used for i.v. urography in
      40 patients, none of whom had complications. No rise in C3d was observed for any
      of the RCM, indicating that complement was not activated. However, significantly
      decreased values for CH50 were detected when the non-ionic RCM iopamidol and
      iohexol were used, and this may be due to interaction between the RCM and the
      complement molecules. Significantly increased numbers of neutrophils were
      observed in patients receiving ioxaglate, iohexol and diatrizoate, which may be
      due to inhibition of granulocyte adherence. No rise in the concentration of
      elastase and lactoferrin was observed. On the other hand, significantly decreased
      values of elastase were seen after injection of diatrizoate, which may be due to
      inhibition of the degranulation process by this media.

PMID- 1999216
TI  - Cystic lymphangioma of the kidney: a rare cause of multiloculated renal masses.

PMID- 1999217
TI  - An analysis of the costs of a hospital-wide Picture Archiving and Communication
      System with the software package CAPACITY.
AB  - Within the scope of the Dutch PACS project, the costs of a hospital wide PACS in
      the Utrecht University Hospital were estimated, with the help of the software
      package CAPACITY. The cost analysis was based on the most recent specifications
      of the costs of the equipment, on extrapolations, and on the experience acquired
      with a PACS prototype in the Utrecht University Hospital. Savings due to a
      possible reduction in the length of stay, or due to logistic improvements were
      not taken into account. The results indicate that the extra costs of a hospital
      wide PACS would amount to 3.2% of the total hospital budget. By taking into
      account the expected price movements, it is predicted that a hospital wide PACS
      may allow enough savings to pay itself back, when installed near the turn of the
      century. The result of this cost analysis depends on a large number of
      assumptions. Therefore two sensitivity analyses are carried out, i.e., concerning
      the number of workstations required and concerning the organizational impact of
      PACS.

PMID- 1999218
TI  - Influence of I-E expression on induction of neonatal transplantation tolerance.
AB  - Neonatal transplantation tolerance was one of the first experimental systems to
      reveal that tolerance could be achieved to non-self antigens in living animals.
      Functional and direct evidence (obtained by the use of monoclonal antibodies
      directed at T cell receptors specifically reactive with I-E molecules) confirm
      that tolerance is achieved, at least in part, via clonal elimination of
      developing thymocytes. In this report, we show that induction of tolerance of
      class I alloantigens in neonatal mice is governed by expression of I-E molecules.
      Neonatal I-E non-expressor mice proved to be highly resistant to the acquisition
      of class I tolerance if the donor inoculum expressed disparate class I antigens
      as well as I-E molecules. The spleens of the few class I-tolerant, I-E non
      expressor mice that were generated were found to be depleted of I-E-reactive
      (RR315+) T cells, whereas no such depletion was observed in their neonatally
      injected, but non-tolerant littermates. By contrast we found no resistance to
      tolerance of I-A alloantigens when neonatal I-E non-expressor mice received
      injections of I-A-disparate, I-E-bearing donor cells. In these tolerant mice,
      splenic I-E-reactive T cells were readily detected in apparently normal amounts.
      These results indicate that lack of I-E expression in newborn mice confers
      resistance to tolerance induction to class I alloantigens, especially when the
      latter are expressed on donor cells that also display I-E molecules. The possible
      mechanisms operating to produce resistance to tolerance induction in neonatal
      mice are discussed, including the possibilities that (a) I-E may act as a
      restricting element during tolerance induction (an ontogenic process), and (b)
      the expression of I-E on H-2-disparate, I-E-expressing test skin allografts may
      provide a source of "help" for CD8+ cytotoxic T cell precursors, leading to graft
      rejection.

PMID- 1999219
TI  - Analysis of a positive feedback mechanism in the anti-Sm autoantibody response of
      MRL/MPJ-lpr/lpr mice.
AB  - The mechanism of induction of anti-Sm antibodies by passive transfer of anti-Sm
      mAb in MRL/lpr mice was investigated. No idiotypic relationship was detected
      between the inducing monoclonal antibody KSm2 and either the induced circulating
      anti-Sm antibodies or the products of anti-Sm-producing hybridomas derived from
      spleen cell fusion of treated mice. Treatment of mice with ribonucleoprotein Sm
      antigen, alone or as an immune complex, induced anti-Sm and anti
      ribonucleoprotein antibodies similarly to treatment with KSm2. This suggests that
      autoantigen contributes to the development of the anti-Sm response in MRL mice.

PMID- 1999220
TI  - Fibronectin associated with infiltrating T lymphocytes. Evidence for in situ
      localization in biopsies and synthesis in vitro.
AB  - Dermal and mucosal lymphocyte infiltrates in patients with lichen ruber planus
      and chronic graft-vs.-host disease exhibited reactivity with anti-fibronectin
      antibodies. This reactivity was associated with the lymphocytes and localized
      pericellularly. In contrast, biopsy areas outside lymphocyte accumulations were
      relatively devoid of reactivity with anti-fibronectin antibodies. Furthermore,
      the corresponding biopsies from healthy individuals or patients without
      lymphocyte infiltration showed negligible reactivity with anti-fibronectin
      antibodies. The fibronectin associated with infiltrating lymphocytes in biopsies
      may be exogenous of non-lymphoid origin. However, another possibility suggested
      by in vitro experiments is that this fibronectin is lymphocyte derived. Thus,
      during cultivation in vitro lymphocytes appear to synthesize a component with
      fibronectin-like properties. Furthermore, a prerequisite for detection of this
      synthesis was that the cells were cultured in the presence of serum depleted of
      fibronectin. These results point to the possibility that fibronectin may play a
      role for lymphocyte interactions with tissues during infiltrative processes.

PMID- 1999221
TI  - Evidence for regulation of naturally activated autoreactive B cells.
AB  - A large fraction of naturally activated B cells in the neonate displays
      degenerate specificity, including reactivity with autoantigens. Transgenic mouse
      models of autoreactive B cells are mainly concerned with monospecific B cells of
      high avidity, and the fate of naturally activated autoreactive B cells is still a
      matter of debate. To pursue this question further, we chose an IgM autoantibody
      with a recurrent idiotype (Id), i.e. Sp6, because transgenic mice expressing this
      IgM also were available. In a first approach monoclonal antibodies (mAb) derived
      from untreated, antigenically stimulated and transgenic mice were used to test
      whether there were indications for deletion or for Id regulation of naturally
      activated autoreactive B cells. Over 90% of thymus and spleen cell derived
      hybridomas from 6-day-old Sp6-transgenic mice were trinitrophenyl (TNP) reactive,
      carried the Sp6-Id and bound to a panel of self antigens, including mouse
      albumin. We failed to obtain B cell hybridomas from the thymus of 28-day-old Sp6
      transgenic mice. Furthermore, we could not detect any mAb carrying an anti-Sp6
      Id, but Sp6 did weakly bind to itself. About 25% of mAb derived from control mice
      displayed degenerate specificity, the majority of them also were TNP reactive.
      The Sp6 Id was found at a low frequency and a comparable number of mAb carried an
      anti-Sp6 Id. Prenatal manipulation at the antigen level (trinitrobenzenesulfonic
      acid treatment) led to a transient expansion of TNP- and autoreactive mAb. The
      number of mAb carrying the Sp6 Id was not increased, but mAb carrying an anti-Sp6
      Id were observed at high frequency. Those mAb also displayed degenerate
      specificity. Since Sp6-transgenic mice were perfectly healthy, it is concluded
      that this particular autoreactive antibody of degenerate specificity cannot be
      harmful for the developing organism, which may possibly be due to its self
      binding capacity. Furthermore, some process of down-regulation was indicated by
      the absence of B cells expressing the transgene in the thymus of young adult
      mice. Autoreactivity of untreated and prenatally antigen-treated mice was, in
      addition, regulated at the Id level. In particular, mAb recognizing the Id of Sp6
      were significantly expanded in antigenically stimulated mice. The data were
      interpreted in the sense that autoreactive B cells appearing early during
      ontogeny were rather strictly controlled either by (functional) clonal deletion
      or by idiotypic connectivity.

PMID- 1999222
TI  - T cell activation in the absence of interleukin 2 (IL 2) results in the induction
      of high-affinity IL 2 receptor unable to transmit a proliferative signal.
AB  - Although interleukin 2 (IL 2) clearly up-regulates the expression of the p55
      chain of the IL 2 receptor (IL 2R) little is known about its role in the
      induction of the high-affinity IL 2R. Resting T lymphocytes were induced to
      express IL 2R under experimental conditions in which IL 2 production was not
      induced or was prevented. Under these conditions high- and low-affinity IL 2R
      were easily demonstrated by Scatchard analysis. Northern blot analysis confirmed
      the accumulation of p55 specific mRNA and the absence of the IL 2 transcript.
      High-affinity IL 2R induced in the complete absence of IL 2 were unable to
      transmit a proliferative response unless exposed to extremely high concentrations
      of IL 2. The addition of picomolar amounts of recombinant IL 2 or the initiation
      of endogenous IL 2 production during the induction period restored the
      functionality of high-affinity IL 2R. Also, T cells induced to generate IL 2
      displayed functional high-affinity IL 2R even in the presence of monoclonal
      antibodies blocking extracellular IL 2 and IL 2R. These results indicate that the
      presence of IL 2 during the early phase of T cell activation is an absolute
      requirement for the induction of fully operational high-affinity IL 2R and that
      low amounts of intracellular IL 2 are sufficient to confer functional properties
      to these receptors. The data also suggest that an intracellular as well as an
      extracellular high-affinity structure, expressed as a consequence of cell
      activation, is responsible for conferring competence to the high-affinity IL 2R
      involved in IL 2-dependent proliferation.

PMID- 1999223
TI  - Formation of covalently linked C3-C3 dimers on IgG immune aggregates.
AB  - Upon activation of the complement system by IgG immune aggregates several
      components become tightly bound to the aggregates. The covalent interaction of C3
      with immune complexes is essential for the solubilization and inhibition of
      immune precipitation of the complexes. It has recently been reported that on
      erythrocytes that have a fixed complement, activated C3 can become involved in
      the formation of C3b-C3b covalent dimers, which acts as high-affinity binding
      sites for C5 (Kinoshita, T., Takata, Y., Kozono, H., Takeda, J., Hong, K. and
      Inoue, K., J. Immunol. 1988 141: 3895). To characterize the molecular composition
      of immune aggregates that have fixed complement by the alternative pathway, we
      have investigated whether such C3b-C3b dimers are formed in IgG immune complexes.
      For this purpose immune aggregates bearing covalently bound C3 were analyzed by
      two-dimensional gel electrophoresis and the resolved bands transferred to
      polyvinylidene difluoride membranes and sequenced. When immune aggregates were
      incubated with serum for 15 min at 37 degrees C, the major high-molecular mass
      bands detected by gel electrophoresis corresponded to heavy chain-C3 alpha 65 and
      C3 alpha 65-C3 alpha 43 (derived from iC3b-iC3b-IgG) covalent complexes. If
      K76COONa, an inhibitor of factor I, was added to the serum, before incubation
      with the immune complexes, then the major C3 alpha fragment detected on the
      complexes corresponded to the C3 alpha' chain (105 kDa) and not C3 alpha 65.
      Hence C3b-C3b covalent dimers are readily formed on the immune aggregates
      incubated with normal human serum, and are degraded to iC3b-iC3b by factor I. The
      second C3b molecule was shown to be bound to the C3 alpha 43 region (C-terminal
      portion of the C3 alpha' chain) of the first C3b molecule, which was itself
      covalently bound to the heavy chain of IgG. Covalent complexes of heavy chain-(C3
      alpha 65)2 molecular composition were also detected, but their precise bonding
      pattern has not been established.

PMID- 1999224
TI  - Preferrential rearrangement in normal rabbits of the 3' VHa allotype gene that is
      deleted in Alicia mutants; somatic hypermutation/conversion may play a major role
      in generating the heterogeneity of rabbit heavy chain variable region sequences.
AB  - The rabbit is unique in having well-defined allotypes in the variable region of
      the heavy chain. Products of the VHa locus, (with alleles a1, a2, and a3),
      account for the majority of the serum immunoglobulins. A small percentage of the
      serum immunoglobulins are a-negative. In 1986, Kelus and Weiss described a
      mutation that depressed the expression of the Ig VH a2 genes in an a1/a2 rabbit.
      From this animal the Alicia rabbit strain was developed and the mutation was
      termed ali. We previously showed, using Southern analysis and the transverse
      alternating field electrophoresis technique, that the difference between the ali
      rabbit and normal is a relatively small deletion including some of the most 3' VH
      genes. The most JH proximal 3' VH1 genes in DNA from normal rabbits of a1, a2 and
      a3 haplotypes encode a1, a2 and a3 molecules respectively, and it has been
      suggested that these genes are responsible for allelic inheritance of VHa
      allotypes. The present study suggests that the 3' end of the VH locus probably
      plays a key role in regulation of VH gene expression in rabbits because VH
      gene(s) in this region are the target(s) of preferential VDJ rearrangements. This
      raises the possibility that mechanisms such as somatic gene conversion and
      hypermutation are at work to generate the antibody repertoire in this species.
      Our data support the view that the 3' VH1 gene may be the preferred target for
      rearrangement in normal rabbits, and for the normal chromosome in heterozygous
      ali animals. However, homozygous ali rabbits with a deletion that removed the a2
      encoding VH1 on both chromosomes do survive, rearrange other VH genes and produce
      normal levels of immunoglobulins as well as a significant percentage of B cells
      which bear the a2 allotype. This challenges the view that one VH gene, VH1, is
      solely responsible for the inheritance pattern of VHa allotypes.

PMID- 1999225
TI  - Regulation of tumor necrosis factor (TNF) release by murine peritoneal
      macrophages: role of cell stimulation and specific phagocytic plasma membrane
      receptors.
AB  - In spite of the physiologic and pathologic importance of tumor necrosis factor
      (TNF), the cellular factors that govern its release by macrophages (M phi) are
      poorly understood, in comparison with other secretory products. We have studied
      the role of M phi heterogeneity and of plasma membrane receptors in regulating
      TNF release in vitro. Resident and various exudate murine peritoneal M phi
      populations were challenged with lipopolysaccharide (LPS) or different phagocytic
      particles, and TNF release assayed by cytotoxicity for L-929 fibroblasts.
      Resident peritoneal M phi (RPM phi) released a small amount of TNF in response to
      LPS whereas thioglycollate-elicited M phi (TPM phi) released high levels of TNF
      (5000 U/3 x 10(5) M phi/ml). M phi elicited by Bio-Gel polyacrylamide beads (BgPM
      phi), another nonspecific inflammatory stimulus, or early in the course of
      intraperitoneal Bacillus Calmette-Guerin infection, before recruited cells become
      immunologically activated, released tenfold less TNF after the same stimulus. By
      contrast, TNF release in response to various phagocytic triggers was similar
      (approximately 300-600 U/3 x 10(5) M phi/ml) in all M phi populations including
      RPM phi. The response by BgPM phi to LPS was enhanced by pre-treatment in vitro
      with interferon-gamma or thioglycollate broth. With respect to phagocytic
      receptor triggering we found that complement receptor type 3 (CR3) ligation or
      latex uptake did not mediate release of significant quantities of TNF (less than
      48 U/3 x 10(5) M phi/ml) by any M phi, whereas ligation of the Fc receptor for
      IgG1/IgG2b subclasses or of receptors for zymosan particles sufficed, in the
      absence of ingestion, to induce release of circa 500 U/3 x 10(5) M phi/ml TNF by
      all M phi tested. Our studies show that M phi vary in respect to priming for TNF
      release and that heterogeneity should be related to a particular triggering
      stimulus. Furthermore, the capacity of some M phi populations to release
      unusually high levels of TNF depends on immune or nonspecific stimuli subsequent
      to the process of inflammatory recruitment.

PMID- 1999226
TI  - Development of lymphocytes in interleukin 7-transgenic mice.
AB  - We have developed and established mouse transgenic lines in which the mouse
      interleukin 7 gene was targeted for expression in the lymphoid cell compartment.
      Northern blot analysis indicate that the transgene is expressed in bone marrow
      (BM), spleen and thymus, but not in kidney, liver, brain or heart. Both the
      frequency and absolute numbers of B cell precursors and mature B lymphocytes are
      increased in the BM and spleen of the transgenic mice. Although there is no
      expansion of the pro-T lymphocyte population in the BM, the number of all major
      subsets of thymocytes and peripheral T lymphocytes is increased in the majority
      of the transgenic mice analyzed. The B and T cell lymphocytes in the transgenic
      mice are functionally competent. In contrast, the number of granulocytes and
      macrophages in the BM of transgenic mice is similar to that in control non
      transgenic littermates. Our results indicate that interleukin 7 plays an
      important role in vivo in the development of B and T lymphocytes.

PMID- 1999228
TI  - Cytotoxicity and immunocyte markers in cells from the freshwater snail
      Planorbarius corneus (L.) (Gastropoda pulmonata): implications for the evolution
      of natural killer cells.
AB  - The hypothesis that natural killer (NK) cells represent an important form of cell
      recognition and cytotoxicity leads to the prediction that NK-like activity should
      be preserved throughout phylogenetic development. This was tested in the
      invertebrate Planorbarius corneus. Two types of cells can be identified and
      separated from the hemolymph of this mollusc, i.e. glass-adherent macrophage-like
      spreading hemocytes (SH) and nonadherent round hemocytes (RH). Only RH are able
      to lyse the K-562 human target cell line in a short-term NK cytotoxicity test.
      This NK-like activity, severely reduced after 18 h incubation at 24 degrees C, is
      preserved by human recombinant interleukin 2. A further analysis of P. corneus
      hemocytes has been performed by using several mouse anti-human monoclonal
      antibodies and cytofluorimetric analysis. Unexpectedly, both SH and RH react with
      several monoclonal antibodies, including those directed against epitopes typical
      of mammalian NK cells and cell adhesion molecules. On the whole, these data
      support the hypothesis that a primitive NK-like activity appeared early in
      evolution and is not shared by phagocytic cells.

PMID- 1999227
TI  - A single-chain murine class I major transplantation antigen.
AB  - Single-chain mouse Kd molecules (SC-Kd) were engineered by connecting residue 276
      of Kd heavy chain to the first residue of beta 2-microglobulin through spacers of
      various lengths, and expressed intracellularly in monkey COS-1 cells. Labeled SC
      Kd molecules were found to react with several monoclonal antibodies which
      recognize native Kd molecules. SC-Kd-15 (with a spacer of 15 residues) was
      studied in more details. It could be purified and shown to regain a native-like
      structure after treatment with denaturing agents. Purified SC-Kd-15 could bind
      certain peptides in a manner qualitatively similar to the Kd.

PMID- 1999229
TI  - Beta 1 integrin-mediated lymphocyte adherence to extracellular matrix is enhanced
      by phorbol ester treatment.
AB  - The interaction of the human T cell leukemia, Jurkat, with the extracellular
      matrix components collagen and fibronectin was examined. These cells displayed
      constitutive binding to fibronectin and low levels of adherence to collagen which
      were enhanced following stimulation with phorbol esters. The relevant binding
      structures were identified as members of the CD29/beta 1 integrin family of
      adhesion molecules. Adherence to collagen and to fibronectin was mediated by
      alpha 2 beta 1 and alpha 5 beta 1, respectively. The enhancement of adherence by
      phorbol esters did not involve up-regulation of receptor expression but appeared
      to derive from the increased functionality of structures which were expressed on
      the cell surface.

PMID- 1999230
TI  - Long-term cross-species brain transplantation of a polymer-encapsulated dopamine
      secreting cell line.
AB  - Cross-species transplantation of dopamine-releasing cell lines protected against
      immune rejection by a semi-permeable synthetic membrane may provide a source of
      neurotransmitters for the treatment of Parkinson's disease. Experiments were
      carried out to assess whether polymer-encapsulated PC12 cells, a
      catecholaminergic cell line derived from a rat pheochromocytoma, could survive in
      vitro as well as in vivo after implantation in the striatum of adult guinea pigs.
      When maintained in vitro, the encapsulated PC12 cells exhibited good survival,
      proliferated, and spontaneously released dopamine for at least 6 months. They
      also retained the capacity for depolarization-elicited dopamine release. In vivo,
      well-preserved tyrosine hydroxylase-positive PC12 cells were observed in capsules
      implanted for 4, 8, and 12 weeks. Unencapsulated PC12 cells or cells in nonintact
      capsules did not survive transplantation at any of these time periods. The
      survival of encapsulated PC12 cells transplanted across species suggests that
      polymer encapsulation may provide an alternative for xenotransplantation of
      secretory cells in the absence of systemic immunosuppression.

PMID- 1999231
TI  - Clinical improvement in parkinsonian patients undergoing adrenal to caudate
      transplantation is not reflected by chromogranin A or basic fibroblast growth
      factor in ventricular fluid.
AB  - Fifteen patients with Parkinson's disease underwent open transplantation of
      autologous adrenal medulla to the caudate nucleus. Motor function was evaluated
      before and after surgery and was found to be significantly improved at 5-9 months
      following surgery. Cerebrospinal fluid was taken from the ventricle adjacent to
      the implant site at the beginning of the operation and at 1 week, 3 months, and 5
      9 months following surgery. The cerebrospinal fluid was assayed for chromogranin
      A (CgA), the major soluble protein in chromaffin granules, and basic fibroblast
      growth factor (bFGF), a neurotrophic growth factor found in normal brain and
      adrenal medulla. CgA levels did not increase following surgery, suggesting that a
      significant number of chromaffin cells did not survive or that surviving
      chromaffin cells did not secrete a significant amount of CgA. Basic fibroblast
      growth factor was undetectable in the ventricular cerebrospinal fluid.

PMID- 1999232
TI  - Neocortical neuronal subpopulations labeled by a monoclonal antibody to calbindin
      exhibit differential vulnerability in Alzheimer's disease.
AB  - Numerous studies have demonstrated that specific neuronal subtypes display a
      differential vulnerability to the pathological process in Alzheimer's disease.
      Large pyramidal neurons are likely to be highly vulnerable, whereas smaller
      neurons are more resistant to pathology. Using a monoclonal antibody to the
      calcium-binding protein calbindin, we observed in the human prefrontal cortex
      distinct populations of labeled cells. First, a subset of heavily stained
      interneurons was located in layers II and superficial III and in layers V-VI.
      Second, a subpopulation of pyramidal neurons in the mid and deep parts of layer
      III displayed a less intense, punctate staining pattern. The interneurons in the
      superficial layers were unaffected in the Alzheimer's disease cases.
      Interestingly, in layers V-VI, there was significant cell loss in the interneuron
      population, but only in the Alzheimer's disease cases with high neurofibrillary
      tangle densities. The calbindin-immunoreactive pyramidal neurons of layer III
      were dramatically affected in the disease. Moreover, there was a strong
      correlation between the extent of the loss of these cells and neurofibrillary
      tangle counts. These data suggest that calbindin is present in multiple neuronal
      subpopulations that exhibit a differential vulnerability in Alzheimer's disease
      and support the hypothesis that the degenerative process involves specific
      neuronal subsets with particular anatomical and molecular profiles.

PMID- 1999233
TI  - Oxygen transport in intraspinal fetal grafts: graft-host relations.
AB  - In the present experiments, we determined tissue oxygen tension (PtO2) levels
      within the injured spinal cords of adult rats following transplantation of fetal
      spinal cord tissue. Partial resection cavities were made at L1-L2 levels after
      which whole pieces of 14-day donor tissue were placed into the cavities. Analysis
      of recordings obtained from graft tissues at 1 and 2 months after transplantation
      revealed low PtO2 values in many cases. Even the more extensively developed
      transplants at 3 months continued to show mean PtO2 levels lower than those taken
      from normal, mature spinal cord tissue. Measurements from host tissue, adjacent
      to a lesion in which no graft was introduced, showed normal or elevated PtO2
      levels. In contrast, where extensive host and graft integration had occurred, the
      PtO2 levels of adjacent host resembled those obtained within the transplants. On
      the other hand, in cases of poor host-graft integration, characterized by either
      cellular or fibrotic graft-host interfaces or large cysts, the PtO2 tensions
      exceeded normal levels. Therefore, the present results show that when fetal
      grafts are placed acutely into an aspiration cavity within the adult spinal cord,
      the transplants quickly establish an oxygen microenvironment resembling that
      found during normal fetal development. Oxygen transport is therefore a regulated
      variable in the graft neuropil as it is in the normally developing spinal cord.
      Furthermore, in the presence of closely approximated fetal transplants, adjacent
      host tissue assumes tissue oxygen levels that mimic those in the graft. This
      "inductive" effect gradually diminishes as development proceeds and may be the
      hallmark of successful graft-host integration.

PMID- 1999234
TI  - Injection of tetrodotoxin into the entorhinal cortex suppresses cell firing in
      the dentate gyrus.
AB  - Ablation of the entorhinal cortex (EC) of rats induces a reorganization of
      afferents and dendrites in the denervated dentate gyrus (DG). The signal which
      triggers these events is unknown, but one candidate is the reduction of granule
      cell firing which follows the EC lesion. Testing this hypothesis requires
      eliminating activity in the perforant path without destroying the EC. In the
      present study, we evaluated whether injecting tetrodotoxin (TTX) into the EC
      could reduce neuronal activity in the DG to the same extent as EC ablation. Using
      microelectrode recording techniques, we recorded the activity of single cells in
      the DG before and up to 8 h after TTX injection. Transmission over the perforant
      path was monitored before and up to 24 h after TTX injections by stimulating the
      EC and recording evoked responses in the DG. TTX injections into the EC
      consistently reduced the firing rate of neurons in the DG by about 80%. Neither
      firing rate nor temporodentate-evoked responses recovered during the observation
      period. Saline injections did not alter either physiological measure. The results
      suggest that the postlesion decreases in neuronal activity in the DG reflect lost
      synaptic drive rather than an effect dependent upon early degenerative events.
      Because TTX injection reduces postsynaptic activity to the same extent as does a
      lesion, the technique can be used to determine whether a loss of afferent drive
      is sufficient to induce the biochemical and morphological sequelae of
      denervation.

PMID- 1999236
TI  - Myotatic reflex development in normal children and children with cerebral palsy.
AB  - Neonatal neuronal exuberance and its retention following neonatal brain damage
      have been demonstrated in a number of species but not in humans. The purpose of
      the present ongoing study is to determine if there is any evidence of neonatal
      neuronal exuberance and its retention following damage to the CNS in the human.
      Of equal concern is the determination of the neurological mechanisms underlying
      abnormal movement and reflex development in children with cerebral palsy.

PMID- 1999235
TI  - Polyamines can protect against ischemia-induced nerve cell death in gerbil
      forebrain.
AB  - We have previously demonstrated that administration of the polyamines putrescine,
      spermidine, or spermine can prevent neuronal degeneration in rats during
      naturally occurring cell death or after injurious treatments such as nerve injury
      or monosodium glutamate neurotoxicity. The present study demonstrates that also
      in adult gerbils polyamine treatment can protect forebrain neurons from
      degeneration after ischemia. Neurons in the hippocampus and striatum were rescued
      from delayed cell death after brief (5 min) global ischemia in gerbils which were
      treated with daily injections (10 mg/kg) of polyamines. The evidence accrued, so
      far, indicates that systemic polyamines can protect a wide variety of central and
      peripheral neurons from natural or induced degeneration.

PMID- 1999237
TI  - Gonyauline: a novel endogenous substance shortening the period of the circadian
      clock of a unicellular alga.
AB  - The circadian clock in the unicellular alga Gonyaulax polyedra is accelerated by
      a substance in extracts from the cells themselves. The extracts have been
      fractionated using the circadian rhythm of bioluminescence as bioassay. The
      active substance, termed gonyauline, has been isolated and characterized as a
      novel low molecular weight cyclopropanecarboxylic acid (S-methyl-cis-2
      (methylthio) cyclopropanecarboxylic acid). Synthetic gonyauline has a similar
      shortening effect on the period of the circadian clock.

PMID- 1999238
TI  - Can we predict the mating pattern of Drosophila females from the sperm length
      distribution in males?
AB  - In order to test the validity of the prediction of the mating pattern of females
      from the sperm length distribution in males, three species of Drosophila were
      analysed. Males in the three species are equally polygynous but females differ in
      the level of polyandry. A 'low recurrence polyandry' is observed in the sperm
      dimorphic species D. affinis while a 'high recurrence polyandry' is observed in
      the sperm monomorphic species D. latifasciaeformis and D. littoralis. These
      results are consistent with the hypothesis proposed previously that sperm
      dimorphism in males can only be maintained by a selective alternative in females
      (i.e. facultative female polygamy), whereas a stricter mating system (e.g.
      'obligatory' polyandry) should only result in sperm monomorphism irrespective of
      the absolute value of sperm length.

PMID- 1999240
TI  - Captivity affects behavioral physiology: plasticity in signaling sexual identity.
AB  - Little is known about the link between captivity, physiology, and behavior in
      wild-caught vertebrates. Anecdotal evidence suggests that hormonal changes are
      responsible for behavioral changes in wild animals brought into captivity.
      Studying the effects of captivity on reproduction is hampered because wild
      animals often fail to exhibit sexual behavior under captive conditions. In weakly
      discharging electric fish, field studies have reported sex differences in
      electric organ discharges which are rarely seen in the laboratory. I now report
      the results of a series of laboratory investigations which show that Gnathonemus
      petersii exhibits seasonal, hormone-dependent, phase-specific sex differences in
      electric organ discharges. Captivity dramatically alters and may even reverse
      these sex differences as a result of rapid changes in endogenous plasma hormone
      levels. These findings have broad implications for research on animal physiology
      and behavior performed in laboratory settings.

PMID- 1999241
TI  - Multiple prismatic calcium phosphate layers in the jaws of present-day sharks
      (Chondrichthyes; Selachii).
AB  - Jaws of large individuals, over 2 m in total length, of the shark species
      Carcharodon carcharias (great white shark) and Isurus oxyrinchus (mako shark) of
      the family Lamnidae, and Galeocerdo cuvieri (tiger shark) and Carcharhinus leucas
      (bull shark) of the family Carcharhinidae were found to have multiple, up to
      five, layers of prismatic calcium phosphate surrounding the cartilages. Smaller
      individuals of these species and other known species of living chondrichthyans
      have only one layer of prismatic calcium phosphate surrounding the cartilages, as
      also do most species of fossil chondrichthyans. Two exceptions are the fossil
      shark genera Xenacanthus and Tamiobatis. Where it is found in living forms, this
      multiple layered calcification does not appear to be phylogenetic, as it appears
      to be lacking in other lamnid and carcharhinid genera and species. Rather it
      appears to be functional, only appearing in larger individuals and species of
      these two groups, and hence may be necessary to strengthen the jaw cartilages of
      such individuals for biting.

PMID- 1999242
TI  - The discovery of antidepressants: a winding path.
AB  - Modern treatment of mental depression started with the availability of monoamine
      oxidase (MAO) inhibitors and tricyclic antidepressants. These drugs also
      contributed to the early development of psychopharmacology. Attempts to improve
      the anti-tuberculous action of the hydrazine derivative isoniazid by developing
      derivatives thereof led to the synthesis of iproniazid. Its introduction as the
      first modern antidepressant was based on three unexpected actions of the drug:
      MAO-inhibition, 'reversal' of reserpine-induced sedation, and the presence of
      psychostimulation as a clinical side effect in man. However, the initial success
      of iproniazid and other MAO inhibitors, hydrazides and non-hydrazides, was
      curtailed by the occurrence of undesirable side effects such as potentiation of
      the blood-pressure elevating action of food amines. The tricyclic antidepressants
      were a development of the class of antihistamines, one of which, chlorpromazine,
      showed neuroleptic activity. A congener of this compound, imipramine, was
      discovered by clinical observation to have unexpected antidepressant effects. The
      clinical success of this drug (which is still in use) led to the development of a
      successful series of other tricyclic and non-tricyclic antidepressants. Progress
      in the elucidation of possible mechanisms of the action of the tricyclic
      compounds has helped this development. Recent advances in basic research have
      also induced a revival of MAO-inhibitors since, due to the discovery of MAO
      subtypes, inhibitors with higher specificity and fewer undesirable side effects
      are now available.

PMID- 1999239
TI  - The human leukemia cell line, THP-1: a multifacetted model for the study of
      monocyte-macrophage differentiation.
AB  - THP-1 is a human monocytic leukemia cell line. After treatment with phorbol
      esters, THP-1 cells differentiate into macrophage-like cells which mimic native
      monocyte-derived macrophages in several respects. Compared to other human myeloid
      cell lines, such as HL-60, U937, KG-1, or HEL cell lines, differentiated THP-1
      cells behave more like native monocyte-derived macrophages. Because of these
      characteristics, the THP-1 cell line provides a valuable model for studying the
      mechanisms involved in macrophage differentiation, and for exploring the
      regulation of macrophage-specific genes as they relate to physiological functions
      displayed by these cells.

PMID- 1999244
TI  - Course of fever response to repeated administration of sublethal doses of
      lipopolysaccharides, polyinosinic:polycytidylic acid and muramyl dipeptide to
      rabbits.
AB  - The purpose of the present study was to examine the development of tolerance to
      three structurally dissimilar pyrogens, i.e., lipopolysaccharide (LPS), muramyl
      dipeptide (MDP) and polyinosinic:polycytidylic acid (poly I:C) in rabbits. The
      possibility of pyrogenic cross-tolerance among these agents has also been
      studied. It was observed that repeated injection of sublethal doses of LPS and
      MDP was connected with the changing of biphasic fever to monophasic. The
      consequence of this was a drop in the fever index. In contrast to LPS and MDP,
      the repeated administration of poly I:C did not result in such changes.
      Successive injections of this pyrogen always evoked biphasic fever. We also
      demonstrated that pyrogenic cross-tolerance between LPS and MDP did not occur.
      The cross-tolerance between LPS and MDP did not occur. The cross-tolerance among
      pyrogens was possible if they originated from the same class, for example
      endotoxin from Salmonella abortus eq. and endotoxin from Escherichia coli.

PMID- 1999243
TI  - Evidence for spontaneous neuro-melanophore activity in Pseudopleuronectes
      americanus (Teleostei; Pleuronectiformes) during total darkness.
AB  - In total darkness, melanophores of much of the integumentary pattern of
      Pseudopleuronectes americanus display intermediate melanosome distribution,
      whilst the alpha-adrenoceptor antagonist phentolamine evokes their complete
      dispersion. The intermediate condition is not attained in total darkness in
      locally decentralized melanophores. It is proposed that, in the absence of photic
      stimulation, spontaneous neural activity sustains a partial melanosome
      aggregation in this species.

PMID- 1999245
TI  - A marine mollusc provides the first example of in vivo storage of prostaglandins:
      prostaglandin-1,15-lactones.
AB  - Prostaglandin-(PG) 1,15-lactones and, in smaller amounts, free acids, were
      isolated from both the mantle and the dorso-lateral appendices of the
      opisthobranch mollusc Tethys fimbria. In vivo conversion of PGs into the
      corresponding lactones and accumulation of PGE2- and PGE3-1,15-lactones in the
      appendages were shown. The detachment of these appendages from the molested
      mollusc caused the in vivo conversion of PGE2- and PGE3-lactones back to PGE2 and
      PGE3 respectively, thus providing the first example of a mechanism by which
      prostaglandins can be stored and, when needed, released.

PMID- 1999246
TI  - Kelletinin I and kelletinin A from the marine mollusc Buccinulum corneum are
      inhibitors of eukaryotic DNA polymerase alpha.
AB  - The inhibitory effect of esters of p-hydroxybenzoic acid (kelletinins I and A),
      extracted from the marine gastropod Buccinulum corneum, have been tested on
      eukaryotic and prokaryotic enzymes of DNA metabolism such as DNA polymerases
      alpha and beta, DNA polymerase I, Exo III, pancreatic DNAse I, micrococcal DNAse
      and E. coli RNA polymerase. Kelletinin I and kelletinin A inhibit preferentially
      DNA polymerase alpha. The inhibitory effect of kelletinin I involves the hydroxyl
      group of p-hydroxybenzoic acid.

PMID- 1999248
TI  - Sexual differentiation of nymphal corpora allata and the effects of ovariectomy
      on adult gland morphometrics in Blattella germanica.
AB  - Changes in the number of corpus allatum (CA) cells were investigated in nymphs
      and in intact and ovariectomized adult female Blattella germanica. The CA of
      intact adult females exhibit cyclic changes in volume in relation to juvenile
      hormone (JH) synthesis, while the CA of ovariectomized females become
      significantly hypertrophied as a result of a gradual and continuous increase in
      volume that is independent of JH biosynthesis. In both intact and ovariectomized
      females changes in JH synthesis and CA volume are not related to total cell
      number which remains relatively constant. However, adult females have twice as
      many CA cells as do adult males as a result of a female-specific increase in
      total cell number late in the last nymphal instar.

PMID- 1999247
TI  - Influence of nocloprost on the vascular responses to various stimuli in the
      isolated perfused rabbit kidney.
AB  - Nocloprost, a new synthetic prostanoid, elicited a vasodilator action when given
      through the renal artery of the isolated perfused rabbit kidney. Lower
      concentrations of the compound inhibited the pressor response to sympathetic
      stimulation or to angiotensin II, but potentiated the pressor effect of exogenous
      noradrenaline. These results were taken as an evidence that nocloprost prevents
      the release of neurotransmitter by a presynaptic mechanism.

PMID- 1999249
TI  - Cyclic and linear vasopressin V1 and V1/V2 antagonists containing arginine in the
      4-position.
AB  - Substitution of arginine for glutamine in the 4-position of a vasopressin V1
      antagonist has been reported to turn it into an agonist. We resynthesized this 4
      arginine analog and synthesized additional cyclic and linear vasopressin
      antagonists containing a 4-arginine. The presence of a 4-arginine in the
      resynthesized and new analogs had relatively minor effects on their
      antivasopressin V1 and V2 antagonistic potencies.

PMID- 1999250
TI  - Adrenal corticosteroidogenesis after removal of ventral prostate gland.

PMID- 1999252
TI  - Mitogenic activity of selenoorganic compounds in human peripheral blood
      leukocytes.
AB  - A variety of organoselenium compounds were originally described as
      antiinflammatory, antioxidant or glutathione-peroxidase-like agents, and as
      inhibitors of prostaglandin and leukotriene synthesis. Recently, the compounds
      have also been found to be inducers of interferon gamma and tumor necrosis factor
      in human peripheral blood leukocytes (PBL). We evaluated the effects of bis [2-(N
      phenylcarboxamido)phenyl] diselenide and Ebselen; 2-phenyl-1,2-benzisoselenazol
      3(2H)one, on the incorporation of tritiated thymidine into the DNA of PBL
      cultured in vitro. Both compounds were mitogenic and this effect was correlated
      with the expression of interleukin 2 receptor in T-lymphocytes. Therefore, we
      suggest that the selenoorganic compounds may induce mitogenic cytokines.

PMID- 1999254
TI  - [The effect of transsection of the inferior alveolar nerve on neurogenic
      inflammation of the oral mucosa. I. Functional studies].
AB  - Vascular effects of local capsaicin treatment has been studied on the 2nd and
      14th days subsequent to unilateral inferior alveolar nerve (IAN) transection in
      the oral mucosa of rats. The results suggest, that the symptoms of neurogenic
      inflammation were influenced by the transection of IAN in a different way. The
      reason of that is the different mechanism in the development of the symptoms
      and/or the different compensatory capacity of the accessorial nerves.

PMID- 1999253
TI  - Relationship between lectin-affinity granules in anuran embryos and formation of
      primordial germ cells.
AB  - Embryos of the anuran, Rana nigromaculata, contained granules with a specific
      affinity for Con A and GS-I. Larvae derived from embryos injected with these
      lectins had a noticeable reduction in both the number and size of primordial germ
      cells (PGCs). This observation suggests that the granules are somehow involved in
      the formation of PGCs.

PMID- 1999251
TI  - The dental amalgam issue. A review.
AB  - Using an interdisciplinary approach, the current position in the dental amalgam
      controversy and the potential impact of amalgam mercury on human health are
      reviewed. Aspects of materials science, corrosion, mercury exposure, toxicology,
      neurology and immunology are included. New data on mercury exposure from corroded
      amalgam fillings in vivo are presented. The exposure can reach levels
      considerably over known threshold limit values. Also, measurements of mercury
      absorption from intraoral air are presented. The vital importance of avoiding a
      galvanic amalgam-gold coupling is emphasized. The symptomatology of a disabled
      patient, who recovered after amalgam removal, has been included. It is concluded
      that discussion of the dental amalgam issue has suffered from the lack of an
      interdisciplinary approach. It would be wise to learn from the lesson of
      acrodynia, and consider amalgam mercury among other possible factors in
      neurological and immunological diseases of unclear etiology.

PMID- 1999255
TI  - [Cranial structure in unilateral complete cleft lip and palate in children 8-12
      years of age].
AB  - The tele-X-ray photographs of 108 patients with single-sided cleft lips and
      palate were compared with 71 normal controls. The examination proved that a basic
      crane structure difference can be found between the groups. The group with cleft
      has a characteristic face with significant skeletal and dental changes. Such
      features have to be considered in the course of habilitation.

PMID- 1999256
TI  - [Computer-assisted teleradiographic image interpretation in orthodontics].
AB  - The utilization of a computer supported cephalometric system using the analysis
      introduced by Hasund is demonstrated. In comparison to the traditional
      measurement by hand the advantages of a computerized analysis are: Time
      reduction, minimization of evaluation errors, the use of individualized norm
      values and the advantages in recording.

PMID- 1999257
TI  - [Average measurements of the mandibular corpus in the planning of jaw
      replacement].
AB  - The height and thicknesses of the mandible corpus at the level of foramen
      mentales, the thicknesses of the mandible base at 3 millimeters from the lower
      edge of the mandible base, the projection length of the mandible corpus and the
      angulus mandibulae were evaluated on jaws coming from 368 anthropological
      collections. No significant differences were found between the measures of the
      right and left side. The differences between corresponding data of men and women
      proved to be significant. The authors intend to use the data for designing and
      preparing jaw replacement models.

PMID- 1999258
TI  - [General aspects of planning fixed dentures on implants].
AB  - Designing of fixed replacements also containing the implant abutment is
      determined by that none of the implant kinds can be regarded as first rate
      abutment tooth in view of loadability. In the course of designing bridges the
      prosthetic principles regarding the weaker or damaged periodontic teeth are
      followed. Burning sensation is a common complaint in the patients suffering from
      a contact allergic reaction of the oral cavity. Several studies are available in
      the literature for testing the allergenicity of dental materials. Standard test
      series were designed to detect allergens present in plastics and metals used in
      prosthetic dentistry. The epicutaneous patch-test was carried out with Finn
      Chamber. The test material was placed into the chamber, which was applied on the
      back of the patients for 24 or 48 hours, and was read after removal at fixed
      intervals. The authors stress the desirability of the allergic prescreening in
      dentistry.

PMID- 1999259
TI  - Interaction of phospholipids with proteins, peptides and amino acids. New
      advances 1987-1989.
AB  - 1. The review deals with the recent achievements in the study of the various
      interactions of phospholipids with proteins, peptides and amino acids. The
      interactions are classified according to the hydrophobic, hydrophilic or mixed
      character of the interactive forces. The effect of the interaction on the
      structure and biological activity of the interacting biomolecules is discussed.

PMID- 1999260
TI  - Resolution of multiple forms of bovine liver arginase by chromatofocusing.
AB  - 1. Bovine liver arginase could be resolved into three distinct peaks by
      chromatofocusing in the pH range 7-4. 2. In other experimental systems the enzyme
      appeared to consist of a single active component. 3. Sodium dodecylsulphate
      polyacrylamide gel electrophoresis revealed a single band which could be assigned
      to arginase, with no indication of inherent or protease-induced multiplicity. 4.
      Lineweaver-Burk plots for arginine were linear over a wide concentration range,
      as were Dixon plots for reversible inhibitors. 5. Covalent inhibition by 1-ethyl
      3-(3-dimethylaminopropyl)-carbodiimide gave semilogarithmic plots of residual
      activity vs time which were strictly linear. 6. It was concluded that the enzyme
      was homogeneous with respect to subunit size and kinetic behaviour, but
      heterogeneous with respect to molecular charge. 7. The charge heterogeneity may
      have kinetic and regulatory implications, as previously suggested for mouse liver
      arginase [Z. Spolarics and J. S. Bond (1988) Archs Biochem. Biophys. 260, 469
      479].

PMID- 1999261
TI  - Effect of chronic ethanol treatment on the t-butyl hydroperoxide-dependent lipid
      peroxidation in rat liver.
AB  - 1. The effect of chronic ethanol consumption on the level of the t-butyl
      hydroperoxide (Bu'OOH)-induced lipid peroxidation in rat liver homogenate and
      subcellular fractions was measured using chemiluminescence technique and
      malondialdehyde formation. 2. It was shown that under the action of ethanol the
      rate of lipid peroxidation was decreased in the whole and "postnuclear" liver
      homogenates. 3. Ethanol significantly decreased the intensity of lipid
      peroxidation in microsomes, but did not affect the Bu'OOH-dependent process in
      mitochondria. 4. The level of lipid peroxidation was reduced after incubation of
      the total particulate fraction (mitochondria plus microsomes) with the undialysed
      cytosol from ethanol-treated rat liver. Dialysis of the cytosol prevented
      depressive effect of ethanol treatment on lipid peroxidation. 5. Reduced
      glutathione (0.1-1.0 mM) was shown to decrease the rate of lipid peroxidation in
      rat liver microsomes, but did not affect its level in mitochondria. 6. Pyrazole
      injections to rats reduced and phenobarbital treatment increased the level of the
      Bu'OOH-dependent lipid peroxidation in liver microsomes. 7. The data obtained
      indicate that the Bu'OOH-dependent lipid peroxidation is not an appropriate
      marker of the ethanol-induced oxidative stress in rat liver cells.

PMID- 1999263
TI  - Interaction of lipogenic substrates in porcine adipose tissue in vitro.
AB  - 1. Porcine adipose tissue was incubated with radiolabeled glucose, acetate or
      lactate. Saturation curves indicated that lactate greater than glucose greater
      than acetate in providing two-carbon units for fatty-acid synthesis. 2.
      Competition between individual substrates indicated that lactate was the best
      lipogenic substrate. 3. Incubation of all three substrates at concentrations
      observable in serum indicated that at 5.56 mM, glucose was the preferred
      lipogenic substrate in the presence of 0.1 mM acetate and 1.0 mM lactate. 4. At
      elevated concentrations (18.52 mM glucose, 1.0 mM acetate and 10.0 mM lactate),
      acetate and lactate were preferred to glucose as lipogenic substrates.

PMID- 1999262
TI  - Biochemical studies of the actions of ethanol on acetylcholinesterase activity:
      ethanol-enzyme-solvent interaction.
AB  - 1. Biochemical studies of the actions of ethanol on the activity of
      acetylcholinesterase (AChE), isolated from electric eel (Electrophorus
      electricus) and purified by affinity chromatography, were performed to elucidate
      ethanol-enzyme-solvent interactions. 2. Ethanol at a low concentration [( EtOH] =
      2.7-200 mM) was found to enhance AChE activity slightly and systematically. 3.
      This observation was consistent with the result from enzyme-kinetic studies that
      ethanol might noncompetitively activate AChE activity at this lower concentration
      range. 4. If ethanol alters the hydrophobic site interaction on the enzyme and
      subsequently induces a favorable conformation for the active center of the
      enzyme, then a slight increase in the AChE activity in the presence of a low
      concentration of ethanol will be observed. 5. This speculation was supported by
      the finding of ethanol's ability to perturb the inhibition of AChE activity by
      tetrabutylammonium bromide and to affect hydrophobic interaction between this
      salt and AChE, as investigated by enzyme activity and microcalorimetric
      measurements. 6. The ethanol effect on the activity of this soluble AChE was
      found to be distinguishable from that on a membrane-bound AChE. 7. Furthermore,
      to elucidate the effect of ethanol-solvent interaction on AChE activity, enzyme
      activity in the presence of much higher concentrations of ethanol was also
      examined. 8. At [EtOH] greater than 800 mM, ethanol can perturb the structure of
      water around hydrophobic areas of AChE, causing an instability in the enzyme
      conformation and subsequently decreasing AChE activity.

PMID- 1999264
TI  - The occurrence and properties of histone H1 zero in quiescent rabbit tissues.
AB  - 1. The issue of the existence and the properties of histone H1 zero in quiescent
      rabbit tissues was approached by electrophoretic, chromatographic and
      immunochemical techniques. 2. The results demonstrated that the rabbit tissues
      did contain a typical histone H1 zero, its properties being comparable to those
      of H1 zero from all other sources studied thus far.

PMID- 1999265
TI  - Nuclear antigen with a molecular weight of 48,000 associated with malignant
      transformation.
AB  - 1. Analysis of immunoblots of one- and two-dimensional electropherograms of non
      histone proteins from Kirkman-Robbins hepatoma, Morris hepatoma 7777,
      regenerating liver and normal liver demonstrated the presence of elevated level
      of nuclear antigen with mol. wt of 48,000 and pI of 5.4 in tumour cells. 2. Small
      amounts only were detected in proliferating and quiescent cells suggesting that
      different expression of this component may reflect biochemical events related to
      malignant transformation rather than to general cell activation.

PMID- 1999266
TI  - A rapid method for detecting DNA strand breaks in Mytilus galloprovincialis Lam.
      induced by genotoxic xenobiotic chemicals.
AB  - 1. In this study, DNA from haemolymph cells of Mytilus galloprovincialis Lam., as
      well as from L1210 (murine leukemia) mouse cells was investigated utilizing the
      technique of the alkaline unwinding of the double stranded DNA molecule. 2. The
      data show that DNA of haemolymph cells from the marine invertebrate has an
      unwinding time and, therefore, a molecular weight considerably lower than that of
      DNA of mammalian cells. 3. The exposure of the cells from mussel haemolymph and
      from mouse L1210 to a genotoxic compound such as dimethylsulfate results in DNA
      damage and consequently in a reduction of the unwinding time. 4. These results
      suggest that the fluorimetric DNA unwinding assay can be used in studies
      concerning the damage of DNA of marine organisms induced by genotoxic compounds
      or environmental factors.

PMID- 1999267
TI  - The combined action of exercise and methylprednisolone sodium succinate on the
      rat gastrocnemius muscle.
AB  - 1. Methylprednisolone sodium succinate (SM) administration reduces the amount of
      contractile proteins and increases the collagen in the rat gastrocnemius muscle;
      it also increases the muscle's isotonic contraction capacity. 2. Exercise in
      combination with SM treatment reduces this capacity and causes also further
      reductions of the contractile proteins and increases of collagen. 3. There are no
      changes of either the relative muscle weight or the number of acetylcholine
      receptors in any experimental group as compared to controls.

PMID- 1999268
TI  - Properties of the isoenzyme forms A-1, A-2 and B of N-acetyl-beta-D
      glucosaminidase purified from baboon kidneys.
AB  - Three forms of N-acetyl-beta-D-glucosaminidase (NAG: A, B and I) were separated
      from baboon kidney using Con A-Sepharose and DEAE-Trisacryl chromatography. 2.
      The A form was further purified into two forms A-1 and A-2 using hydroxylapatite
      chromatography and anodic PAGE. Both were homogeneous on SDS-PAGE and anodic PAGE
      but microheterogeneous on PAG-IEF, which could be eliminated by prior treatment
      with endoglycosidase H or glycopeptidase F. 3. The carbohydrate content accounted
      for some of this microheterogeneity since it varied from 31 for A-1 to 17% for A
      2 and the sialic acid was 6 and 1%. Deamidation may also contribute since the
      acidic amino acids (29 mol%) and ammonia were high following acid hydrolysis. 4.
      The mol. wt for A-1, determined by SDS-PAGE, was 52.1 K. 5. The pH optimum was
      4.55 and the pI4.97. 6. The optimum temperature for NAG A and B was 50 degrees
      and 42 degrees C, but B retained more activity above 55 degrees C. 7. The Km for
      N-acetyl-beta-D-glucosamine and -galactosamine for both isoforms was 0.497 and
      0.627 mM respectively. 8. Several ions were found to be uncompetitive inhibitors.
      Ag+ and Pb2+ were the most potent having Ki values of 3.6 and 8.5 mM
      respectively. Acetate acted as a competitive inhibitor.

PMID- 1999269
TI  - Is islet amyloid polypeptide a significant factor in pathogenesis or
      pathophysiology of diabetes?
AB  - Islet amyloid polypeptide (IAPP) or amylin, a recently discovered minor secretory
      peptide of the beta-cell related to calcitonin gene-related peptide (CGRP), is a
      constituent of amyloid deposits in the islets of many non-insulin-dependent (type
      II) diabetic individuals and some elderly nondiabetic subjects. IAPP is
      synthesized as a small precursor at a level of approximately 1% that of insulin
      and is processed, amidated, stored in beta-granules, and released along with
      insulin and C-peptide. Analysis of its gene (located on chromosome 12) supports
      an evolutionary relationship to calcitonin and CGRP, peptides with which it
      shares some biological actions. Like CGRP, IAPP antagonizes the action of insulin
      mainly at the level of muscle glycogen synthesis, but the levels required for
      this effect seem to be considerably higher than reported circulating levels. No
      evidence for overproduction of IAPP in diabetic subjects has been found thus far,
      but much more work is necessary to define its normal secretory rates and
      clearance. Other proposed actions of IAPP include serum calcium-lowering effects
      and smooth muscle relaxation; the latter effect might promote the uptake of
      insulin into the circulation within the islets. Deposition of amyloid is species
      selective due to structural differences within the central part of the molecule
      and may be initiated intracellularly in type II diabetes by several mechanisms.
      No differences in the structure of IAPP or its precursor have been found in
      individuals with maturity-onset diabetes of the young or type II
      diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1999270
TI  - Newly identified pancreatic protein islet amyloid polypeptide. What is its
      relationship to diabetes?
AB  - Islet amyloid polypeptide (IAPP) or amylin is a newly identified 37-amino acid
      COOH-terminal-amidated polypeptide that is the major protein constituent of
      amyloid deposits in insulinomas and amyloid deposits in pancreatic islets of non
      insulin-dependent (type II) diabetic humans and adult diabetic cats. IAPP is
      stored with insulin in beta-cell secretory vesicles and is cosecreted with
      insulin in response to glucose and several secretagogues. IAPP has been
      demonstrated in normal pancreatic islets of many species, but IAPP-derived
      amyloid develops commonly in the islets of only a few species (e.g., humans and
      cats), especially in association with age-related diabetes. IAPP from the human
      and cat inherently contains a short amyloidogenic sequence that is not present in
      species that do not form islet amyloid. Studies in animals indicate that an
      aberration in the synthesis or processing of IAPP, leading to a local increase in
      concentration of IAPP in the islet, is also required to facilitate the conversion
      of IAPP to amyloid. The formation of islet amyloid may contribute to the
      development of type II diabetes by causing disruption of islet cells and by
      replacement of islets. It has also been proposed that an abnormality of IAPP
      homeostasis underlies the pathogenesis of type II diabetes. A significant causal
      relationship between IAPP and type II diabetes is based on reports that IAPP
      inhibits glucose-stimulated insulin release by beta-cells and that IAPP inhibits
      insulin-stimulated rates of glycogen synthesis and glucose uptake by skeletal
      muscle cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1999271
TI  - Peptide-based radioimmunoassay specific for GLUT1 glucose transporter.
AB  - A radioimmunoassay for the GLUT1 glucose transporter was developed with a
      synthesized peptide based on the sequence of the cDNA for GLUT1. A peptide
      corresponding to the COOH-terminal domain of the GLUT1 glucose transporter (Thr
      Pro-Glu-Glu-Leu-Phe-His-Pro-Leu-Gly-Ala-Asp-Ser-Gln-Val) was synthesized and
      conjugated to keyhole limpet hemocyanin through the NH2-terminal of the peptide.
      An antibody was raised against this complex and affinity purified with the
      immobilized peptide. A second peptide, with tyrosine residue added to the NH2
      terminal of the above peptide, was synthesized and used as a standard and
      iodinated for preparation of the radioactive ligand. The assay is highly
      reproducible, sensitive, and specific for the COOH-terminal domain of the GLUT1
      glucose transporter. It has no cross-reactivity with the other glucose
      transporter isoforms GLUT2 and GLUT4. Furthermore, the results obtained with this
      radioimmunoassay on the number of glucose transporters in human erythrocytes were
      in good agreement with previous studies based on cytochalasin B binding,
      suggesting that this radioimmunoassay is able to quantify the number of glucose
      transporters. The assay is completed within 4 h and can be used for simultaneous
      measurement of GLUT1 in many samples. In addition, it can be applied to the
      measurement of GLUT1 in several types of tissue.

PMID- 1999272
TI  - Islet cell antibodies in patients with autoimmune thyroid disease.
AB  - Islet cell antibodies (ICAs) were assayed in 316 patients with autoimmune thyroid
      disease (AITD; 190 with Graves' disease, 126 with Hashimoto's thyroiditis), 53
      patients with insulin-dependent diabetes mellitus (IDDM), and 144 healthy control
      subjects. ICAs were measured by an immunohistochemical method with peroxidase
      labeled protein A and human pancreatic tissues. The prevalence of ICAs in
      patients with AITD was 7.6% (24 of 316), whereas the prevalence in control
      subjects was 0.7% (1 of 144). Among 24 ICA+ patients, 20 (83%) had IDDM. In these
      20 patients, the duration of diabetes from clinical onset was 5.4 +/- 5.1 yr.
      ICAs in patients with IDDM alone were positive in 90.9% at 1 yr and 7.7% at 5 yr
      after the onset of diabetes. These data have shown that most ICA+ patients with
      AITD have IDDM and that the prevalence of ICAs in patients with AITD in Japanese
      is as high as that found among whites, whereas the incidence of IDDM in Japanese
      is approximately one-thirtieth or one-fiftieth of that in whites.

PMID- 1999273
TI  - Effects of IP3, spermine, and Mg2+ on regulation of Ca2+ transport by endoplasmic
      reticulum and mitochondria in permeabilized pancreatic islets.
AB  - Inositol 1,4,5-trisphosphate (IP3) increased the free-Ca2+ concentration in the
      incubation medium of permeabilized ob/ob mouse pancreatic islets. Spermine
      decreased the free-Ca2+ concentration through stimulation of mitochondrial Ca2+
      uptake and attenuated the effect of IP3. Mg2+ antagonized the effects of
      spermine, thereby increasing the free-Ca2+ concentration and enhancing the effect
      of IP3 on the free-Ca2+ concentration. Because IP3 releases Ca2+ from endoplasmic
      reticulum, these results indicate that endoplasmic reticulum and mitochondria can
      interact in the regulation of the free-Ca2+ concentration in the cytosol of the
      pancreatic beta-cell.

PMID- 1999274
TI  - Content of CoA-esters in perifused rat islets stimulated by glucose and other
      fuels.
AB  - Fluorometry and high-performance liquid chromatography were used to measure the
      content of free CoA and the esters of acetate, malonate, succinate, and long
      chain fatty acids in isolated perifused rat pancreatic islets exposed to 25 mM
      glucose or a mixture of fuels (25 mM glucose plus 10 mM glutamine, 10 mM lactate,
      and 1 mM pyruvate) to assess the role of intermediates of lipid metabolism as
      candidate metabolic coupling factors in the mechanism of fuel-induced insulin
      secretion. Insulin secretion was stimulated in a biphasic manner with the fuel
      mixture, showing twice the potency compared with high glucose alone. Islets
      perifused for 3 min with high glucose alone or the fuel mixture compared with 2.5
      mM glucose showed a significant increase in malonyl-CoA and succinyl-CoA and a
      decrease in acetyl-CoA. Free CoA and long-chain acyl-CoA levels were unaltered.
      Perifused islets stimulated with 25 mM glucose for 30 min showed a significant
      increase in succinyl-CoA and long-chain acyl-CoA and decrease in acetyl-CoA,
      whereas malonyl-CoA was not affected. However, when islets were stimulated by the
      fuel mixture for 30 min, malonyl-CoA was maintained at a high level, and the
      change in succinyl-CoA and long-chain acyl-CoA was similar to that observed in
      islets stimulated with 25 mM glucose alone. The acetyl-CoA concentration in the
      islets stimulated with the fuel mixture decreased slightly. These results confirm
      the viability of the hypothesis that malonyl-CoA and long-chain acyl-CoA serve as
      metabolic coupling factors in signal transduction when islets are stimulated by
      high glucose or glucose combined with other fuels.

PMID- 1999275
TI  - Frequency and effects of apolipoprotein E polymorphism in Mexican-American NIDDM
      subjects.
AB  - We typed 254 non-insulin-dependent diabetic (NIDDM) Mexican Americans living in
      Starr County, Texas, for the three common apolipoprotein E (apoE) alleles. Typing
      was performed via DNA amplification and Hha I restriction. The allele frequencies
      (epsilon 2 = 0.041, epsilon 3 = 0.860, epsilon 4 = 0.099) were in Hardy-Weinberg
      equilibrium (chi 2 = 0.60, df = 3) and did not differ from a random sample from
      the same population (chi 2 = 0.16, df = 2). Analysis of variance was used to test
      for mean differences in lipid, lipoprotein, and glucose levels among apoE types.
      Significant differences among types were detected for low-density lipoprotein
      cholesterol (LDL-chol; P = 0.042, R2 = 2.6) and beta-lipoprotein cholesterol (P =
      0.019, R2 = 3.3) levels. Mean LDL-chol in E2/3 individuals was 2.69 mM, E3/3 was
      3.26 mM, and E4/3 was 3.36 mM. Mean beta-lipoprotein cholesterol in E2/3
      individuals was 3.05 mM, E3/3 was 3.64 mM, and E4/3 was 3.67 mM. Based on these
      results, we conclude that the effects of the apoE polymorphism on lipid profiles
      and glucose levels are the same in NIDDM subjects as in nondiabetic Mexican
      Americans and other populations. Other studies investigating the role of apoE
      polymorphism in diabetic subjects have found increased triglyceride levels in
      individuals possessing an epsilon 2-allele and an increased frequency of the
      epsilon 2-allele in hyperlipidemic diabetic subjects. We found no significant
      difference in mean triglyceride levels among genotypes. Possible reasons for this
      discrepancy are discussed, including DNA- versus protein-typing methods.

PMID- 1999276
TI  - Blunted diuretic and natriuretic responses to central administration of clonidine
      in streptozocin-induced diabetic rats.
AB  - The purpose of this study was to determine whether diuretic and natriuretic
      effects are altered in response to intracerebroventricular (ICV) infusion of
      clonidine in diabetic rats. Diabetes was induced in male Sprague-Dawley rats by
      65 mg/kg i.p. injection of streptozocin, and control rats were injected with
      vehicle 2 wk before the experiment. Blood glucose levels were significantly
      elevated in the diabetic group (26.3 +/- 1.3 mM) compared with the control group
      (8.4 +/- 1.6 mM). Before and during ICV infusion of clonidine (2 micrograms.kg
      1.min-1 for 45 min), urine flow and sodium excretion were measured from intact
      and denervated kidneys in anesthetized diabetic and control rats. The ICV
      infusion of clonidine significantly increased urine flow in both innervated and
      denervated kidneys from control rats but not from diabetic rats. There was a
      significant increase in sodium excretion during ICV infusion of clonidine from
      innervated kidneys of control rats, and denervation abolished this effect. In
      diabetic rats, clonidine failed to promote natriuresis from intact kidneys, and
      similar to control rats, did not promote natriuresis in denervated kidneys. This
      study demonstrates that 1) the diuretic response to the ICV infusion of clonidine
      is blunted in diabetic rats, and 2) a natriuretic response to the ICV infusion of
      clonidine is blunted in innervated kidneys of diabetic rats.

PMID- 1999277
TI  - Lack of evidence for improvement in long-term glycemic control by pulsatile
      insulin infusion in streptozocin-induced diabetic baboon.
AB  - To assess the potential therapeutic use of pulsatile intravenous insulin
      delivery, five streptozocin-induced diabetic baboons were treated with alternate
      3- to 6-wk periods of pulsatile and continuous insulin infusion. Time-averaged
      insulin concentrations were matched during two pulsatile administration periods
      (P1 and P2) and an intervening period of continuous insulin administration (C).
      There were no significant differences among the overall means of four daily
      glucose determinations performed during the three periods (P1, 5.7 +/- 1 mM; C,
      5.6 +/- 0.9 mM; P2, 5.3 +/- 0.9 mM); the mean M value, a measure of the stability
      of glycemic control (P1, 4 +/- 1.7; C, 3.9 +/- 1.8; P2, 3.6 +/- 1.5); the
      percentage of glucose values less than 2.8 mM (P1, 13 +/- 8.5%; C, 14 +/- 12%;
      P2, 13 +/- 9.1%); or the glycosylated hemoglobin levels determined at the end of
      the P1 and C (7.5 +/- 3.4 and 6.5 +/- 1.8%, respectively [all values are means +/
      SD]). Fasting hepatic glucose production was suppressed to a similar degree
      during pulsatile and continuous insulin infusion (P1, 23 +/- 3 mumol.kg-1.min-1;
      C, 24 +/- 8 mumol.kg-1.min-1). Arterial glucagon levels were similar during
      pulsatile and continuous insulin infusion, both in the fasting state (84 +/- 29
      and 84 +/- 31 ng/L, respectively) and postprandially (30 +/- 14 and 27 +/- 12
      ng/L, respectively). Pulsatile insulin infusion failed to entrain a corresponding
      glucagon secretory rhythm. These data suggest that the metabolic consequences of
      long-term pulsatile and continuous insulin infusion in an animal model of human
      non-insulin-dependent diabetes are comparable.

PMID- 1999278
TI  - Independent effects of youth and poor diabetes control on responses to
      hypoglycemia in children.
AB  - To evaluate the effects of childhood and poorly controlled insulin-dependent
      diabetes mellitus (IDDM) on counterregulatory hormone and symptomatic responses
      to hypoglycemia, we studied 16 nondiabetic children (13 +/- 2 yr), 19 nondiabetic
      adults (26 +/- 3 yr), and 13 children with IDDM (14 +/- 2 yr, HbA, 15.1 +/- 3.3%)
      during a gradual reduction in plasma glucose with the glucose-clamp technique.
      Plasma glucose was reduced from approximately 5 to approximately 2.8 mM over 240
      min with serial assessment of counterregulatory hormone levels and symptom
      awareness. The plasma glucose level that triggered a sustained rise in plasma
      epinephrine was consistently higher in nondiabetic children than in adults (3.9
      +/- 0.06 vs. 3.2 +/- 0.06 mM, P less than 0.001). Poorly controlled IDDM further
      elevated the glucose threshold for epinephrine release to normoglycemic levels
      (4.9 +/- 0.2 mM, P less than 0.001 vs. both control groups). Age and IDDM also
      produced an upward shift in the glucose level at which growth hormone release and
      symptom awareness were initiated. In contrast to the effect on glucose
      thresholds, maximal epinephrine responses and symptom scores were increased only
      by age and not IDDM (2-fold higher in children). We conclude that childhood and
      poor diabetes control independently contribute to an upward shift in glucose
      thresholds for counterregulatory hormone release and symptom awareness during
      mild hypoglycemia. Normoglycemic counterregulation may interfere with efforts to
      control diabetes in young patients.

PMID- 1999279
TI  - Interaction of ascorbic acid and glucose on production of collagen and
      proteoglycan by fibroblasts.
AB  - Collagen and proteoglycans are two major constituents of the extracellular
      matrix, and their abnormalities have been incriminated in the pathogenesis of
      diabetic complications. A decrease of plasma ascorbic acid has been reported in
      diabetes and thus may play a role in the collagen and proteoglycan abnormalities
      in diabetes. Ascorbic acid and glucose share structural similarity, and their
      metabolism may interact at the level of membrane transport and cellular action.
      In this study, we used a fibroblast culture system to explore this possibility.
      Ascorbic acid increased collagen and proteoglycan both in the culture medium and
      the cell layer. This stimulatory action of ascorbic acid was inhibited by the
      presence of glucose at a concentration of 25 mM. The effect of high glucose
      concentration was not mediated by inhibition of ascorbic acid uptake by
      fibroblasts. Insulin is able to abolish this inhibitory action of glucose on
      collagen production, but the precise mechanism is unclear. These results show
      that the high glucose concentration in diabetes can impair the action of ascorbic
      acid at the cellular level. This may further accentuate the problem of decreased
      availability of this vitamin as a result of its low plasma concentration.

PMID- 1999280
TI  - Use of X-ray diffraction in study of human diabetic and aging collagen.
AB  - Extensive investigations of the solubility and fluorescence of collagen fibers in
      diabetes have revealed that there are significant changes in their physical
      properties. These changes are associated with increased cross-link formation. We
      used X-ray diffraction to study these changes in human extensor tendons at a
      molecular level in relation to both aging and diabetes. Our results indicate that
      diabetes induces significant alterations in the ultrastructure of collagen in the
      lateral packing of the molecules and the axial structure of the specimen. These
      changes can be induced in normal tendon by incubation in ribose and glucose-6
      phosphate but are different from those associated with the normal process of
      aging.

PMID- 1999281
TI  - The pleiotropic UGA35(DURL) regulatory gene of Saccharomyces cerevisiae: cloning,
      sequence and identity with the DAL81 gene.
AB  - The UGA35 gene of Saccharomyces cerevisiae (also called DURL) encodes a positive
      regulator of the expression of structural genes involved in 4-aminobutyric acid
      (GABA) and urea catabolisms. The UGA35 gene has been cloned by complementation of
      function and identified by chromosomal gene replacement. The sequence of this
      regulatory gene and its flanking regions has been established. Our data reveal an
      open reading frame of 2892 nt, corresponding to 964 amino acids (aa). The deduced
      UGA35 aa sequence shares several similarities with that of other regulatory
      proteins, suggesting that the UGA35 gene encodes a DNA-binding transcriptional
      activator. We also show that UGA35 and the DAL81 regulatory gene controlling
      allantoin and urea catabolisms are one and the same gene. This means that the
      same factor is required for specific induction of three distinct catabolic
      pathways, namely those involved in GABA, urea and allantoin utilization as
      nitrogen sources.

PMID- 1999282
TI  - A DNA fragment containing the ADE2 gene from Schwanniomyces occidentalis can be
      maintained as an extrachromosomal element.
AB  - A 4.05-kb DNA fragment containing the ADE2 gene from Schwanniomyces occidentalis
      was cloned into the pUC19 vector. When an ade2 strain of Sc. occidentalis was
      transformed with this plasmid, pADE-2 was found to integrate into the host
      chromosome and was also present in a variety of extrachromosomal species. These
      extrachromosomal elements were present in multiple copies, varied in molecular
      mass and were composed of polymerized forms of pADE-2. A fragment containing the
      ADE2 gene was used to transform a Sc. occidentalis ade2 mutant, as either a
      linear or circularized molecule. The linear form integrated into the host genome,
      whereas the circularized form was found as a stably maintained extrachromosomal
      element with no evidence of integration or detectable loss of the Ade+ phenotype
      upon subculturing of transformed yeast under nonselective conditions for 60
      generations. The ratio of the number of extrachromosomal ADE2 genes to genomic
      ADE2 ranged from 3.8 to 6.6.

PMID- 1999283
TI  - Cloning of several lignin peroxidase (LIP)-encoding genes: sequence analysis of
      the LIP6 gene from the white-rot basidiomycete, Phanerochaete chrysosporium.
AB  - A Phanerochaete chrysosporium BKMF1767 genomic library, constructed in the BamHI
      site of vector YRp12, was screened with the lignin peroxidase(LIP)-encoding
      cDNAs, CLG4 and CLG5, that have been shown to encode LIP2 (previously H2) and
      LIP6 (previously H10), respectively. Six distinct LIP genomic clones, designated
      pGLG1, pGLG2, pGLG3, pGLG4, pGLG5, and pGLG6, were isolated in this study. Probe
      CLG4 hybridized only to pGLG1. Probe CLG5 gave intense hybridization to pGLG2 and
      weaker hybridization to clones pGLG3 through pGLG6, but showed little or no
      hybridization to pGLG1. These results, in agreement with previous biochemical
      results, indicate the existence of LIP gene subfamilies. The limits and
      transcriptional orientation of the LIP gene in each clone were determined. The
      sequence data showed that pGLG2 contains the LIP6 gene, which encodes a protein
      identical in amino acid (aa) composition to that encoded by CLG5. It contains a
      leader sequence of 27 aa and a mature protein of 344 aa (Mr 36,607). Archetypal
      TATA-box-like and CAAT-box-like sequences in the 5'-noncoding region are located
      51 and 97 nt upstream from the cDNA start point, respectively. S1 nuclease
      analysis of the 5' region of LIP6 revealed two transcription start points 8 nt
      apart downstream from the TATA box. Comparison of the sequence of LIP6 with its
      corresponding cDNA CLG5 showed that the gene contains nine small introns which
      range in size from 50 to 62 bp. These introns contained consensus splice junction
      sequences similar to those reported in other fungal and yeast introns.

PMID- 1999284
TI  - Vaccinia virus-like early transcriptional control sequences flank an early gene
      in orf virus.
AB  - The purpose of this study was to map the initiation (tsp) and termination points
      of transcripts arising from an open reading frame (ORF3) found in the inverted
      terminal repeat of the orf virus genome and also, to identify probable
      transcriptional control sequences. Early transcripts of approx. 0.76 kb were
      mapped to ORF3 and found to be transcribed toward the ends of the genome. Using
      the S1 nuclease and primer-extension methods, the bulk of the tsp were mapped to
      a position 12-13 nucleotides (nt) downstream from a sequence which resembles A +
      T-rich vaccinia virus early promoters. The 5' ends were 81-82 nt upstream from
      the first ATG in ORF3. Most of 3' ends of the transcripts mapped to a region 24
      32 nt downstream from a T5NT sequence found near the ORF3 stop codon. A second
      transcription termination point was found 25 nt downstream from another T5NT
      sequence located downstream and separated by 85 nt from the first. These results
      infer that the A + T-rich, early transcriptional control sequences found in other
      poxvirus genomes have been conserved in the G + C-rich genome of orf virus.

PMID- 1999285
TI  - Rat urate oxidase: cloning and structural analysis of the gene and 5'-flanking
      region.
AB  - The structural gene (UOX) encoding rat urate oxidase (UOX) spans at least 23 kb
      and is composed of eight exons and seven introns. All of the exon-intron splice
      junction sequences conformed to the GT/AG consensus established for eukaryotic
      genes. The transcription start point (tsp) was determined using S1-type nuclease
      protection riboprobe, and assigned to an adenine 54 nucleotides (nt) upstream of
      the ATG start codon. A 456-bp 5'-terminal fragment, starting at the ATG codon,
      carries a putative TATA (ATAAAA) sequence at -32, and two putative 'CAAT box'
      sequences at -62 and -71 bp upstream from the tsp. No sequence resembling 'GC'
      box hexanucleotides (GGGCGG or CCGCCC) was found. The structural features of the
      5'-flanking region of the UOX gene are distinct from the 5'-flanking sequences of
      peroxisomal beta-oxidation system genes which contain one or more 'GC' box
      elements but lack TATA- and CAAT-like features [Osumi et al., J. Biol. Chem. 262
      (1987) 8138-8143; Ishii et al., J. Biol. Chem. 262 (1987) 8144-8150]. The 5'
      flanking region of the UOX gene reveals a sequence, TTAGTAATT at nt -276 from the
      tsp, which appears to be complementary to the underlined part of the liver
      specific LF-B1/HNF-1 consensus sequence, GTTAATNATTAAC (where N = A, C, T, G or
      no nt).

PMID- 1999286
TI  - Cloning and nucleotide sequence of the chimpanzee c-myc gene.
AB  - A DNA fragment covering the chimpanzee c-myc locus was cloned from the DNA of
      peripheral blood lymphocytes, sequenced, and compared to its human c-myc
      counterpart. The two nucleotide sequences were found to be highly homologous
      (99%). The divergence rate between the two species was 0.4% in exons and 1.7% in
      introns. The different TATA-boxes described in the human myc gene were also
      identified in the chimpanzee sequence and an open reading frame (ORF) was
      observed which overlaps the chimpanzee c-myc first exon. This latter ORF
      contained three silent mutations with regard to the human region, whereas the
      chimpanzee Myc oncoprotein coded by exons 2 and 3 differed by two amino acids
      from the human one.

PMID- 1999287
TI  - Genetic recombination in a chromosomal translocation t(2;8)(p11;q24) of a
      Burkitt's lymphoma cell line, KOBK101.
AB  - We analyzed a chromosomal translocation, t(2;8)(p11;q24), in a Burkitt's lymphoma
      cell line, KOBK101. The translocation reciprocally occurred between a site about
      150 bp upstream from the J5 segment in the Ig kappa-encoding gene on chromosome 2
      and the A-rich end of an Alu repetitive element located far downstream from the c
      myc gene on chromosome 8. Short segments of both parental chromosomes were
      deleted at the rearrangement site. A sequence related to the heptamer recognition
      signal for the V-J recombination of Ig genes and a topoisomerase I-recognition
      sequence were detected at the breakpoints. The V-J recombination occurred on both
      chromosome 2 and the translocated chromosome 2p- at the J3 and J4 segments,
      respectively. The J region on the translocated chromosomes was mutated, as
      compared with that on the untranslocated chromosome, while the Alu element and
      its upstream sequence were conserved. These results suggest the following aspects
      to the chromosomal translocation of this cell line. A V-J recombination seems to
      have occurred at the proximal end of the J4 segment first, and then the
      translocation took place in the region between the J4 and J5 segments. The
      translocation may have been mediated by the functions of topoisomerase I and the
      Alu repetitive sequence located at the breakpoint, although the possibility
      cannot be ruled out that the recombination machinery for Ig gene rearrangements
      functioned irregularly.

PMID- 1999288
TI  - Characterization of two novel human retropseudogenes related to the calmodulin
      encoding gene, CaMII.
AB  - Two human genomic clones (lambda hg22 and lambda hg29), containing two novel
      calmodulin (CaM) retropseudogenes, were isolated and characterized. The two
      pseudogenes show high similarity with the human CaMII cDNA, hCE1 [SenGupta et
      al., J. Biol. Chem. 262 (1987) 16663-16670] and the CaMII-type retropseudogene,
      hCE2 (CaMII-psi 1) [SenGupta et al., Nucleic Acids Res. 17 (1989) 2868]. One of
      them, in clone lambda hg22 (CaMII-psi 2), shows all the characteristics of a
      processed pseudogene. In clone lambda hg29 (CaMII-psi 3), however, an Alu
      repetitive sequence was detected immediately upstream from the ancestral 5'
      untranslated region. Downstream from the truncated 3'-untranslated region, three
      additional copies of Alu repetitive sequences flanking about 750 nucleotides of
      unknown origin were found. Such a processed retropseudogene flanked by multiple
      Alu repeats may be a target for further recombination events. The three
      retropseudogenes CaMII-psi 1, CaMII-psi 2 and CaMII-psi 3 are estimated to be
      about 49, 21 and 25 million years old, respectively.

PMID- 1999290
TI  - Use of a dual-origin temperature-controlled amplifiable replicon for optimization
      of human interleukin-1 beta synthesis in Escherichia coli.
AB  - A new dual-replicon recombinant plasmid, pPR53-tsr, has been constructed; it is a
      derivative of the expression vector pPR-TGATG-1 [Mashko et al., Gene 88 (1990)
      121-126]. In contrast to its progenitor, pPR53-tsr is a low-copy-number (low-Cop)
      plasmid amplifiable in temperature-dependent fashion. In addition to both the
      replicon and the par locus from plasmid pSC101, providing segregational stability
      and a low Cop at 28 degrees C, the new plasmid contains a mutant ColE1 replicon
      whose RNAII is synthesized under the control of the pL promoter. The presence of
      a thermolabile repressor, cIts857, allows the thermo-inducible amplification of
      pPR53-tsr; the increased plasmid Cop is estimated at approx. 200 per genome 6 h
      after thermal induction at 42 degrees C. Thus, pPR53-tsr can be used as a donor
      of the thermo-inducible dual-replicon fragment for recombinant plasmids. Here, we
      employ such an approach for optimization of production of human interleukin-1
      beta (hIL-1 beta) in Escherichia coli at a high level. The thermo-induced level
      of recombinant hIL-1 beta (re-hIL-1 beta) biosynthesis was around 9% of total
      cellular protein when the dual-replicon high-Cop vector was used. A method based
      on acidification of the water-soluble protein fraction to pH 4.0 has been
      developed that allows for the isolation of 80%-pure re-hIL-1 beta. The
      homogeneous material was obtained by two subsequent hydrophobic sorbent
      chromatographies. The protein yield ranged between 3-5 mg of re-hIL-1 beta/g of
      wet cells. The re-hIL-1 beta specific activity was about 2 x 10(8) units/mg,
      coinciding with that of the authentic hIL-1 beta.

PMID- 1999289
TI  - Human interleukin 1 beta fused to the human growth hormone signal peptide is N
      glycosylated and secreted by Chinese hamster ovary cells.
AB  - A hybrid gene consisting of the sequences coding for the signal peptide of human
      growth hormone and the mature form of interleukin-1 beta (IL-1 beta) was
      chemically synthesized. This sequence was inserted into a eukaryotic expression
      vector and introduced into Chinese hamster ovary cells. The resulting stably
      transformed cell lines produced large amounts of recombinant IL-1 beta, which was
      secreted into the culture medium mainly as a 22-kDa form. Expression in the
      presence of tunicamycin, an inhibitor of N-glycosylation, led to the complete
      disappearance of the 22-kDa form and the appearance of a new form of 17.5 kDa,
      indicating that the hybrid protein had been both processed and N-glycosylated.
      However, transformed cells producing mature IL-1 beta without a signal peptide
      produced the predicted 17.5-kDa nonglycosylated form. These results suggest that
      fusion to a heterologous leader sequence allowed IL-1 beta to be translocated
      across the membrane of the endoplasmic reticulum and to be transported and
      secreted by the exocytotic pathway.

PMID- 1999291
TI  - Cloning of trichosanthin cDNA and its expression in Escherichia coli.
AB  - Several cDNA clones coding for trichosanthin (TCS) have been isolated from a cDNA
      library prepared from the poly(A)+RNA of the root tuber of Trichosanthes
      kirilowii Maximowicz. The nucleotide sequence codes for a protein of 289 amino
      acids (aa) including a putative signal peptide of 23 aa and an extra 19 aa at the
      C terminus; the latter two have not been found in TCS obtained from the natural
      product [Collins et al., J. Biol. Chem. 265 (1990) 8665-8669]. Recombinant TCS
      (reTCS) was synthesized in Escherichia coli, in which the cDNA without the signal
      sequence was expressed under the control of the trc promoter; reTCS was detected
      by a rabbit anti-TCS antiserum.

PMID- 1999292
TI  - Cloning and expression in vitro of a gene encoding tRNAArgACG from the nematode
      Caenorhabditis elegans.
AB  - A gene (rtr-1) coding for the tRNAArgACG has been isolated and characterized from
      the nematode, Caenorhabditis elegans. The coding portion is not interrupted by an
      intron and is followed by a track of four thymidines associated with termination
      by RNA polymerase III. The predicted mature product is 76 nucleotides (nt) long
      including the CCA tail, and is specific for the most used Arg codon in C.
      elegans. The gene can be transcribed and processed in a homologous in vitro
      system. The 82-nt primary transcript begins at the first purine upstream from the
      mature tRNA 5' end and terminates after the first thymidine of the terminator
      signal.

PMID- 1999293
TI  - Structural organization of the murine gene encoding NAD-dependent
      methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase.
AB  - The structural organization of the entire nuclear gene (NMDMC) encoding the
      mitochondrial (mt) NAD-dependent methylenetetrahydrofolate dehydrogenase
      methenyltetrahydrofolate cyclohydrolase enzyme (NMDMC) was determined by analysis
      of clones obtained from a lambda EMBL3 murine genomic DNA library. The gene is
      approx. 13 kb in length and contains eight exons and seven introns. All
      exon/intron splice junctions follow the GT/AG rule. The amino acid presequence,
      which is essential for transport of the NMDMC enzyme precursor into mt, is
      encoded almost entirely in the first exon. Two major transcriptional start points
      (tsp), located 33 and 75 nucleotides upstream from the AUG start codon, were
      revealed by S1 nuclease mapping and RNase protection analyses. The immediate 5'
      flanking region of the first exon contains one CAAT box, a TATA-like box and
      three sites homologous to the consensus sequence for the binding of transcription
      factor Sp1.

PMID- 1999294
TI  - A nuclear factor requires Zn2+ to bind a regulatory MRE element of the mouse gene
      encoding metallothionein-1.
AB  - The metal ion requirement of nuclear proteins for binding to the metal regulatory
      element d(MREd) of the mouse gene encoding metallothionein-1 was investigated
      using an in vitro exonuclease III footprinting assay. The specific DNA-binding
      activity of the factor was inactivated by the chelating agents, EDTA and 1,10
      phenanthroline. Binding activity was restored by Zn2+, but not by Cd2+. These
      results show that Zn2+ ions are a required component for specific in vitro DNA
      binding of the MREd-binding protein.

PMID- 1999295
TI  - Structure of the gene encoding rabbit beta-casein.
AB  - The entire rabbit beta-casein-encoding gene and 400 bp upstream were sequenced.
      Eight introns, located essentially at a position similar to the corresponding
      gene in other species, were found. Strong homology with several casein-encoding
      genes from rabbit and from other species was observed in the upstream region of
      the gene. Repeated sequences of unknown function were also located within
      introns.

PMID- 1999296
TI  - Private giving essential to society's future.

PMID- 1999297
TI  - Are inadequate medical records undermining care of the elderly?

PMID- 1999298
TI  - Managing geriatric arrhythmias, I: General considerations.
AB  - Cardiac arrhythmias become increasingly common as people age, but they are not
      always clinically significant. Sinus node dysfunction, AV conduction
      disturbances, and ventricular and supraventricular arrhythmias will be found but
      are not always symptomatic. Treatment of asymptomatic arrhythmias is
      controversial and probably not indicated, but in symptomatic elderly, therapy is
      indicated, since even the very elderly have been found to benefit from it as much
      as younger patients. There are specific guidelines, however, that apply to this
      age group based on its susceptibility to side effects.

PMID- 1999299
TI  - Alzheimer's disease: answering questions commonly asked by patients' families.
AB  - Once a diagnosis of Alzheimer's disease is made, the patient's family usually has
      a number of questions for the physician. These questions range from concerns
      about genetic aspects of the disease to specific caregiving issues. The primary
      care physician's role in treating Alzheimer's disease is focused on the family or
      caregiver and includes support and counseling. Providing answers to common
      questions is an important part of counseling.

PMID- 1999300
TI  - Pain control in the ambulatory elderly.
AB  - Pain control in the elderly, no matter what the etiology or setting, can be a
      major clinical challenge. Aging causes unique physiologic changes, eg, a
      decreased perception of pain and an enhanced sensitivity to opioid analgesics.
      Principles regarding evaluation of patients with pain are reviewed, including the
      use of an objective instrument for pain assessment from the viewpoint of both
      physician and patient. Good pain control can be achieved with the nonopioids,
      such as acetaminophen and the nonsteroidal anti-inflammatory drugs, the opioid
      analgesics, and, in some cases, adjuvant agents. Discussed also are the concerns
      for patient addiction and the WHO Cancer Pain Relief program.

PMID- 1999301
TI  - Dry mouth: diagnosing and treating its multiple causes.
AB  - Dry mouth in the elderly is a common occurrence with multiple etiologies. It is
      not a normal phenomenon of aging and, therefore, an attempt at elucidating its
      cause should be made. Sjogren's syndrome may occur, and it is diagnosed by labial
      biopsy. Medications are also frequently associated with dry mouth, and dosages
      may need to be adjusted or the drug discontinued if symptoms are severe.
      Strategies for management of dry mouth are explored.

PMID- 1999302
TI  - Geriatric constipation: brief update on a common problem.
AB  - Constipation occurs frequently in the elderly and is often multifactorial in
      origin. A search for an underlying cause is necessary, and can often be found by
      taking an adequate history and performing a thorough physical examination. A
      minority of patients require further investigation, guided by the clinical
      setting. Management should be directed at correcting the underlying cause and
      providing dietary advice and, less commonly, medication to allow restoration of a
      normal bowel habit.

PMID- 1999303
TI  - Factors to consider in nursing home placement.
AB  - Nursing home placement is a difficult decision for all involved, and there are
      several important reasons to pursue alternatives, if at all possible. The
      principles of maximizing function and identifying services to support patients in
      an independent living environment are a high priority for the elderly and the
      physicians caring for them. Many techniques and resources are available to
      physicians to help fulfill this role. When alternatives are no longer feasible
      and nursing home placement is indicated, the physician can provide a variety of
      types of support, information, and guidance to patients and their caregivers.

PMID- 1999304
TI  - The migration of acrylonitrile from acrylonitrile/butadiene/styrene polymers into
      food-simulating liquids.
AB  - The correlation of residual acrylonitrile (AN) monomer concentration in AN
      containing polymers with AN migration into food simulants is of interest because
      the US FDA regulates the use of these polymers on the basis of the amount of AN
      that may migrate into food simulants. Studies of the migration of AN into water
      from seven acrylonitrile/butadiene/styrene polymers with varying composition and
      residual AN levels showed that a linear relationship exists between the
      concentration of AN in the polymer and the amount of AN migrating, for a given
      set of exposure conditions. A linear relationship was also observed between the
      diffusion coefficients generated from the experimental data using a simple
      Fickian diffusion model and the inverse of the absolute temperature of exposure.

PMID- 1999305
TI  - Chemical oxidation and metabolism of N-methyl-N-formylhydrazine. Evidence for
      diazenium and radical intermediates.
AB  - N-Methyl N-formlhydrazine (1), a component of the mushroom Gyromitra esculenta,
      is a carcinogen. Its mode of action, however, is poorly understood. To determine
      the intermediates that may form during the metabolism of 1, we examined its
      oxidative chemistry, identified the products and inferred the intermediates on
      the basis of these products. The incubation of 1 with rat liver microsomes was
      also studied and the metabolites determined and quantified. Both the chemical and
      the microsome-mediated oxidation of 1 yielded formaldehyde and acetaldehyde. The
      formation of acetaldehyde requires (i) the oxidation of 1 to a diazenium ion (I)
      or diazene (II) and (ii) fragmentation of I/II to formyl and methyl radicals. It
      is suggested that these radical intermediates may be important in understanding
      and elucidating carcinogenesis by 1.

PMID- 1999306
TI  - Interspecies variations in response to topical application of selected zinc
      compounds.
AB  - The dermal irritancy of six zinc compounds was examined in three animal models.
      In open patch tests involving five daily applications, zinc chloride (1% aqueous
      solution) was severely irritant in rabbit, guinea-pig and mouse tests, inducing
      epidermal hyperplasia and ulceration; aqueous zinc acetate (20%) was slightly
      less irritant. Zinc oxide (20% suspension dilute Tween 80), zinc sulphate (1%
      aqueous solution) and zinc pyrithione (20% suspension) were not overtly irritant,
      but induced a marginal epidermal hyperplasia and increased hair growth. Zinc
      undecylenate (20% suspension) was not irritant. Epidermal irritancy in these
      studies is related to the interaction of zinc ion with epidermal keratin. The
      compounds studied were not consistently bacteriostatic in the three species
      tested.

PMID- 1999307
TI  - New brands of oral snuff.
AB  - Snuff dipping is causally related to cancer of the oral cavity and pharynx. The
      most powerful carcinogens in snuff are nitroso compounds, particularly the
      tobacco-specific N-nitrosamines (TSNA). Concentrations of TSNA in snuff exceed
      the known concentrations of carcinogenic nitrosamines in any other consumer
      product by two to three orders of magnitude. During the last decade a gradual
      decrease in TSNA has occurred in the two leading snuff brands in the USA (about
      90% of the market). Of two recently introduced snuff brands one has relatively
      low levels of nitroso compounds while the other contains the highest
      concentrations of nitrosamines ever reported in smokeless tobacco. This
      observation suggests that control of nitrosamines in snuff brands on the US
      market is desirable.

PMID- 1999308
TI  - Chronic toxicity/carcinogenicity studies of cocoa powder in rats.
AB  - Cocoa powder (CP) was fed at levels of 0.0 (control), 1.5, 3.5 and 5.0% for 104
      wk to male and female Sprague-Dawley rats derived from the F3b generation of a
      multigeneration study using the same CP diets. Initial methylxanthine intake was
      high in all treatment groups, but steadily declined until wk 26. The high dose
      level provided a mean methylxanthine intake of approximately 57 mg/kg body
      weight/day for males and 74 mg/kg body weight/day for females from wk 26 to wk
      104 of the study. Compared with controls, the historical trend of methylxanthine
      associated growth stimulation was evident in rats consuming diets containing 1.5%
      CP, while body weight was reduced in rats consuming diets containing 3.5 and 5.0%
      CP. Survival rates were similar in control and CP-fed rats. No evidence of
      treatment-related clinical disease or ocular effects was noted. An increased
      incidence of bilateral testicular atrophy and aspermatogenesis was present in
      males consuming diets containing 5.0% CP. Non-suppurative myocarditis and
      interstitial fibrosis of the heart were also increased in incidence in both sexes
      receiving diets containing 5.0% CP. The overall incidences of both pelvic
      dilatation and renal pelvic microcalculi were increased in most treatment groups.
      Although there was no difference in the incidence of benign mammary gland
      fibroadenomas in female rats between the control group and any CP-fed group, a
      marginally significant (P = 0.04) trend test was apparent. The significance of
      this finding is doubtful, since the incidence of this lesion in the highest dose
      group was well within the historical control range for this strain of rats. No
      evidence of carcinogenicity from dietary CP was found in either sex.

PMID- 1999309
TI  - Sweetener intakes.

PMID- 1999310
TI  - Some comments on the dietary intake of butylated hydroxytoluene.

PMID- 1999311
TI  - Hyposensitivity to vasopressin in patients with hepatitis B-related cirrhosis
      during acute variceal hemorrhage.
AB  - It has been suggested that vasopressin given during hemorrhage may be less
      effective than when given during a stable state in a portal-hypertensive rat
      model. This study was designed to evaluate the hemodynamic response to
      vasopressin infusion in 25 HBsAg-positive cirrhotic patients. Nine patients had
      active variceal hemorrhage before vasopressin infusion, and the other 16 patients
      were in a stable condition at the time of infusion. The two groups of patients
      were similar in baseline values except that a higher heart rate was found in
      patients with hemorrhage (96 +/- 20 vs. 73 +/- 10 beats/min, mean +/- S.D., p
      less than 0.01). Thirty minutes after vasopressin infusion (0.66 units/min),
      hepatic venous pressure gradient significantly decreased in both bleeding and
      stable patients (from 21 +/- 9 to 18 +/- 9 mm Hg, p less than 0.05; and from 18
      +/- 4 to 8 +/- 3 mm Hg, p less than 0.0001, respectively). However, the decrease
      of hepatic venous pressure gradient was less obvious in bleeding patients as
      compared with stable patients (4 +/- 3 vs. 9 +/- 2 mm Hg, p less than 0.0001). A
      significant reduction of hepatic venous pressure gradient after vasopressin
      infusion was found in five bleeding patients without shock (from a median of 16
      mm Hg [range = 12 to 26] to 11 mm Hg [range = 6 to 18], p less than 0.05), but
      not in four bleeding patients with shock (from 28 [range = 15 to 36] to 25 [range
      = 18 to 33] mm Hg, p greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1999313
TI  - Expression of X protein and hepatitis B virus replication in chronic hepatitis.
AB  - The X protein can act on the enhancer of hepatitis B virus in an in vitro system
      and elevate the transcriptional level of hepatitis B virus. However, because no
      relationship had been reported between X protein expression and hepatitis B virus
      replication in patients with chronic hepatitis B, we focused on its expression in
      the liver in comparison with markers of hepatitis B virus replication. Liver
      biopsy samples and sera from 59 carriers with HBsAg were examined
      immunohistochemically for X protein using rabbit IgG against recombinant X
      protein. There was a significant difference in the serum hepatitis B virus DNA
      level between X protein-positive and -negative patients (p less than 0.001).
      Serum pre-S1 and pre-S2 antigens were also measured quantitatively by enzyme
      immunoassay using monoclonal antibodies specific against each antigen. The titers
      of pre-S1 antigen in patients positive for X protein were significantly higher (p
      less than 0.001) than those of the X protein-negative patients (3.02 +/- 0.99 vs.
      2.00 +/- 0.59, respectively). Similarly, the titers of pre-S2 antigen were 2.98
      +/- 0.91 vs. 1.94 +/- 0.54, respectively (p less than 0.001). The rate of
      positivity of the X protein was higher (38 of 49; 77.6%) in the replicative group
      (serum HBeAg, serum hepatitis B virus DNA or HBcAg in liver positive) compared
      with that observed in the nonreplicative group (3 of 10; 30%--serum HBeAg, serum
      hepatitis B virus DNA and HBcAg in liver negative) (p less than 0.01).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1999312
TI  - Hepatitis B virus replication modulates pathogenesis of hepatitis D virus in
      chronic hepatitis D.
AB  - Hepatitis D virus and hepatitis B virus nucleic acids were detected by Northern
      and Southern blot hybridization in the sera and livers of 85 chronic carriers of
      HBsAg and anti-hepatitis D followed up for a mean of 10 yr. We identified three
      subsets of patients: 13 with hepatitis D virus and hepatitis B virus viremia, 53
      with serum hepatitis D virus RNA, but without hepatitis B virus DNA and 19
      negative for both nucleic acids. Genomic and subgenomic forms of hepatitis D
      virus RNA were detected only in patients with hepatitis D virus and hepatitis B
      virus viremia. Histological findings and disease activity at admission were
      comparable in the three groups of patients, but the outcome was significantly
      worse in patients with active replication of both viruses; two of them died of
      terminal liver failure and hepatocellular carcinoma developed in two; the
      remaining patients had an uneventful course. These results suggest that active
      hepatitis B virus replication represents an important previously unrecognized
      determinant of severe liver damage in patients with chronic hepatitis D virus
      infection. Since hepatitis B virus provides the means for hepatitis D virus
      secretion and release from infected cells, active hepatitis B virus
      multiplication favoring the spread of hepatitis D virus from cell to cell may
      increase the pathogenetic potential of the defective agent.

PMID- 1999314
TI  - Increased lysophosphatidylcholine and pancreatic enzyme content in bile of
      patients with anomalous pancreaticobiliary ductal junction.
AB  - A high incidence of inflammation and carcinoma of the biliary tract in patients
      with anomalous pancreaticobiliary ductal junction has been well documented. The
      change in biliary phospholipids as a result of the reflux of pancreatic juice
      into the biliary tract through anomalous pancreaticobiliary ductal junction may
      be responsible for it. We developed a new method of analysis of phospholipid
      classes using aminopropyl Bond Elut cartridge for extraction and high-performance
      liquid chromatography for separation. Satisfactory recovery was achieved (i.e.,
      more than 95% for both phosphatidylcholine and lysophosphatidylcholine). With
      this method, the bile of 11 patients with anomalous pancreaticobiliary ductal
      junction was examined. The concentration and proportion of
      lysophosphatidylcholine in bile were much higher in the presence of anomalous
      pancreaticobiliary ductal junction than in controls (3.44 +/- 1.50 mmol/L vs.
      0.52 +/- 0.25 mmol/L, 60.0% +/- 31.0% vs. 2.3% +/- 1.4% in gallbladder bile; p
      less than 0.001). In contrast, the concentration of phosphatidylcholine and the
      sum of phosphatidylcholine and lysophosphatidylcholine in gallbladder bile
      significantly decreased (p less than 0.001), but in hepatic bile they did not. An
      inverse correlation was found between the proportion of lysophosphatidylcholine
      and phospholipid concentration in gallbladder bile. Phospholipase A2 and amylase
      activities in bile were markedly high. Increased total fatty acid concentration
      and proportion of unsaturated fatty acid in bile were found. Total bile acid
      concentration in gallbladder bile was significantly lower than in controls. These
      results suggest that a considerable amount of lysophosphatidylcholine, which is
      known to have a cytotoxic effect, isp reduced by phospholipase A2 in refluxing
      pancreatic juice, and an increased concentration of lysophosphatidylcholine gives
      rise to cell damage causing mucosal hyperplasia and metaplasia.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1999315
TI  - The role of methanethiol in the pathogenesis of hepatic encephalopathy.
AB  - Mixed disulfides of methanethiol represent a relative estimate for an exposure to
      methanethiol. The concentrations of methanethiol-mixed disulfides, methionine, 4
      methylthio-2-oxobutyrate and ammonia were measured in patients with different
      stages of hepatic encephalopathy, in patients with chronic kidney failure and in
      healthy subjects. In patients with hepatic encephalopathy, the mean serum
      concentrations of all these compounds were elevated. However, the elevations of
      methanethiol-mixed disulfides were small and partly caused by decreased renal
      function. In addition, the levels of methanethiol-mixed disulfides did not differ
      significantly between the different grades of hepatic encephalopathy. The
      concentrations of methanethiol-mixed disulfides were substantially lower than
      those previously observed in healthy subjects after an oral methionine load or in
      a patient with a deficiency in methionine adenosyltransferase, the latter without
      causing encephalopathy. We concluded that the role of methanethiol in the
      pathogenesis of hepatic encephalopathy is probably minor, if not insignificant.
      In the patients with hepatic encephalopathy, a significant correlation was found
      between the concentrations of methionine and 4-methylthio-2-oxobutyrate and
      between 4-methylthio-2-oxobutyrate and methanethiol-mixed disulfides, supporting
      the theory that methanethiol is formed by way of the methionine transamination
      pathway. Evidence is provided that, besides the methionine transsulfuration
      pathway, the transamination pathway is also impaired in patients with hepatic
      encephalopathy.

PMID- 1999316
TI  - Markers of chronic alcohol ingestion in patients with nonalcoholic
      steatohepatitis: an aid to diagnosis.
AB  - We report here the use of the biochemical marker desialylated transferrin to aid
      in the diagnosis of nonalcoholic steatohepatitis. Conventional biochemical tests
      used for the detection of chronic alcohol consumption fail to differentiate
      nonalcoholic steatohepatitis patients from alcoholic subjects. In addition, even
      in those alcoholic subjects with alcoholic liver disease in whom biopsy has been
      performed, it is impossible to differentiate these two disease states on the
      basis of morphological examination alone. In this study we have examined two new
      markers of excessive alcohol intake, desialylated transferrin and mitochondrial
      AST in subjects with nonalcoholic steatohepatitis and in patients consuming
      excessive amounts of alcohol. All nonalcoholic steatohepatitis patients consumed
      minimal or no alcohol and were diagnosed by morphological criteria based on liver
      biopsy specimens. Alcoholic subjects were consuming in excess of 80 gm/day
      ethanol, often with clinical evidence of overt alcoholism. Control subjects
      included both healthy controls and patient controls with liver diseases unrelated
      to alcohol. The ratio of desialylated transferrin/total transferrin was elevated
      only in patients who consumed excessive amounts of alcohol, whereas the ratio of
      mitochondrial AST to total AST (mitochondrial AST/total AST) was not
      significantly different between alcoholic subjects and patients with nonalcoholic
      steatohepatitis. The sensitivity and specificity for the ratio desialylated
      transferrin/total transferrin was 81% and 98%, respectively, whereas the
      sensitivity for the mitochondrial AST/total AST ratio was 92%; the specificity
      was only 50%, indicating that there were a large number of false-positives. All
      the conventional markers were less sensitive and less specific than the ratio
      desialylated transferrin/total transferrin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1999317
TI  - Hepatic amino-nitrogen clearance to urea-nitrogen in control subjects and in
      patients with cirrhosis: a simplified method.
AB  - The functional hepatic nitrogen clearance during amino acid infusion is a measure
      of liver cell mass. The clinical feasibility of the test has so far been limited
      by methodological problems. A simplified procedure was used to measure the urea
      nitrogen synthesis rate and functional hepatic nitrogen clearance in nine
      subjects with normal liver function and in nine patients with cirrhosis. The
      method was based on only four consecutive 2-hr urine collections and five blood
      samples. Total body water was calculated from a nomogram based on age and
      anthropometric data, whereas the gut urea hydrolysis was assigned one fixed
      fraction of synthesis (0.17 in control subjects and 0.26 in patients with
      cirrhosis). Finally, a solution of a single amino acid, alanine, was infused as
      substrate for urea synthesis. Urea-nitrogen synthesis rate increased linearly
      with increasing alpha-amino-nitrogen concentration, and the slope of the
      regression (functional hepatic nitrogen clearance) was reduced in cirrhosis from
      37.5 +/- 7.0 L/hr to 18.4 +/- 6.7 L/hr; p less than 0.005. The hepatic nitrogen
      clearance was linearly related to the clinical status (Child-Pugh score), to
      routine liver function tests and to galactose elimination capacity (r = 0.869), a
      well-established, quantitative, liver function measure. The simplified method
      makes the measurement of hepatic nitrogen clearance suitable for routine clinical
      use. The test might prove useful to study the alterations of nitrogen metabolism
      in cirrhosis, with special reference to hepatic encephalopathy.

PMID- 1999318
TI  - Autoantibodies in primary biliary cirrhosis: analysis of reactivity against
      eukaryotic and prokaryotic 2-oxo acid dehydrogenase complexes.
AB  - Six components of the mammalian 2-oxo acid dehydrogenase complexes have
      previously been identified as M2 autoantigens in primary biliary cirrhosis. In
      this report, we present data showing that both polypeptide-specific and cross
      reacting antibodies are present in patients' sera. Antibodies reacting with E2 of
      the pyruvate dehydrogenase complex cross-react with protein X but not with any
      other mammalian antigen. The main immunogenic region on protein X has been
      localized to within its single lipoyl domain. Polypeptide-specific antibodies
      bind to E1 alpha and E1 beta of the pyruvate dehydrogenase complex. Antibodies
      reacting with the E2 polypeptides of the 2-oxoglutarate dehydrogenase complex and
      branched-chain 2-oxo acid dehydrogenase complex show some cross-reactivity but do
      not recognize any of the antigens of the pyruvate dehydrogenase complex.
      Antibodies against the E2 component of the mammalian pyruvate dehydrogenase
      complex cross-react effectively with the corresponding protein from yeast but not
      with E2 from Escherichia coli. Antibody titer against mammalian antigens is
      significantly higher than against the bacterial antigens, arguing against a
      bacterial origin for primary biliary cirrhosis.

PMID- 1999319
TI  - The sensitized liver represents a rich source of endogenous leukotrienes.
AB  - The ability of livers to produce endogenous leukotrienes after immunological
      stimulation was tested with organs from rats and guinea pigs. Passive
      sensitization of rats in vivo with monoclonal murine antidinitrophenol-IgE before
      antigen challenge in the isolated perfused liver system elicited a rapid hepatic
      production and biliary excretion of leukotrienes as judged by radioimmunoassay
      after separation of individual leukotrienes by high-performance liquid
      chromatography. Within 10 min after antigen infusion, mainly leukotriene C4, but
      also leukotriene D4 and N-acetyl-leukotriene E4, appeared in the bile. The
      biliary excretion rate of antigen-induced cysteinyl leukotrienes rose from less
      than 2 pmol.min-1.(kg body mass)-1 before challenge to about 30 pmol.min-1.(kg
      body mass)-1 for 20 min before it declined toward prechallenge level.
      Quantitatively similar hepatic production of cysteinyl leukotrienes was elicited
      in isolated perfused guinea pig livers challenged with ovalbumin after active
      sensitization of the animals with ovalbumin plus Al(OH)3. To exclude extrahepatic
      contributions to the observed leukotriene production, both passive sensitization
      with anti-dinitrophenol-IgE and subsequent antigen challenge were performed on
      isolated rat livers perfused with blood-free medium. Such exclusively hepatic
      sensitization and challenge also resulted in massive production of leukotrienes.
      The biliary excretion rate of cysteinyl leukotrienes amounted to approximately 20
      pmol.min-1.(kg body mass)-1 during the 10 to 20 min period after antigen
      challenge as compared with less than 1 pmol.min-1.(kg body mass)-1 before
      challenge.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1999320
TI  - Hypothermic preservation of hepatocytes. III. Effects of resuspension media on
      viability after up to 7 days of storage.
AB  - Hepatocyte suspensions provide a rapid method to determine how hypothermic
      storage affects liver cell metabolism and viability. Using these studies,
      improved methods of hypothermic liver preservation for transplantation may be
      developed. In this study, rat hepatocytes were cold-stored for up to 7 days in
      University of Wisconsin liver preservation solution. At the end of each day of
      storage hepatocytes were resuspended in Krebs-Henseleit buffer or tissue-culture
      medium (Liebovitz-15; Fischer's; modified Fischer's, which was similar to
      Fischer's but with glycine and cysteine added; or Waymouth's medium). Hepatocyte
      viability was assessed by rewarming and oxygenating the suspensions and measuring
      the percentage of leakage of lactate dehydrogenase from the cells, the cellular
      concentration of potassium and the stimulation of respiration by succinate, all
      measures of plasma membrane integrity. Additionally, concentrations of ATP and
      glutathione after rewarming and reoxygenation in the various resuspension media
      were measured. Hepatocyte permeability to lactate dehydrogenase did not increase
      during cold storage of 1 to 7 days (7.2% +/- 2% leakage), indicating that most of
      the hepatocytes remained viable during cold storage. However, when rewarmed, loss
      of viability (leakage of lactate dehydrogenase) was dependent on the composition
      of the resuspension media. In Krebs-Henseleit buffer, viability was reduced after
      2 and 3 days of storage (lactate dehydrogenase leakage on rewarming = 70% to
      90%). Leakage of lactate dehydrogenase was reduced significantly after
      resuspension in tissue-culture media. After 6 days of storage, lactate
      dehydrogenase leakage from hepatocytes stored in Liebovitz- 15 or modified
      Fischer's was only about 30%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1999321
TI  - Ethanol increases the formation of NADP+ in rat hepatocytes.
AB  - The acute effects of ethanol on total (bound + free) pyridine dinucleotides were
      determined in freshly isolated rat hepatocytes. Pyridine dinucleotides and
      adenine nucleotides were determined by high-performance liquid chromatography.
      Exposure of the hepatocytes to 8 mmol/L ethanol resulted in a decrease in NAD+
      and an increase in NADP+ after 2 min incubation. There were no significant
      changes in NADH and NADPH. Ethanol decreased ATP and increased AMP after 2 min,
      whereas an increase in ADP was only apparent after 15 min of incubation. Ethanol
      8 mmol/L and 100 mmol/L resulted in an increased incorporation of [32P] into
      NADP+ from [32P]-prelabeled NAD+ and ATP. Ethanol increased hepatocyte NAD+
      kinase activity; this effect was blocked by 4-methylpyrazole but reproduced by 10
      mumol acetaldehyde. These observations indicate that ethanol increases the
      synthesis of NADP+ and that this effect is most likely the result of increased
      NAD+ kinase activity. The ethanol-induced decrease of NAD+ may limit ADP
      ribosylation of nuclear proteins, whereas increases in NADP+ may stimulate the
      pentose phosphate cycle.

PMID- 1999322
TI  - Rapid induction of hepatic fibrosis in the gerbil after the parenteral
      administration of iron-dextran complex.
AB  - The parenteral administration of iron-dextran complex to gerbils caused hepatic
      hemosiderosis and fibrosis after 6 wk. Type I and III collagen synthesis in the
      liver developed from perisinusoidal stellate cells that are often referred to as
      myofibroblasts. Immunohistologically these cells were shown to have large
      intracellular deposits of ferritin. The hepatic fibrosis appeared to be
      associated with aggregates of these cells rather than the aggregates of Kupffer
      cells, which also occur in hemosiderosis in the liver. No appreciable necrosis of
      hepatocytes to trigger the fibrotic response was found, so that the fibrosis
      appeared to be related to the accumulation of ferritin in the perisinusoidal
      stellate cells. In contrast, rats and mice did not accumulate ferritin in their
      perisinusoidal cells or develop hepatic fibrosis in response to parenterally
      administered iron, although they accumulated similar or greater amounts of total
      iron in their livers. The rapid induction of hepatic fibrosis in gerbils in
      response to parenterally administered iron will provide a model to investigate
      the mechanism of induction of collagen deposition in response to iron overload
      and a means of quickly evaluating therapeutic treatments for iron overload
      induced fibrosis in vivo using iron-chelating drugs.

PMID- 1999323
TI  - Hypercholeresis induced by unconjugated bile acid infusion correlates with
      recovery in bile of unconjugated bile acids.
AB  - Using the isolated perfused rat and hamster liver, the relationship between bile
      flow, bile acid secretion rate and bile acid biotransformation after the
      injection of a small, bolus dose of radioactive ursodeoxycholate or of its C23
      homolog, norursodeoxycholate, was examined. Ursodeoxycholate was promptly
      secreted into bile mostly as amino acid conjugates; less than 3% was secreted in
      unchanged form in the rat and less than 2% in the hamster. In contrast,
      norursodeoxycholate was secreted slowly, and biotransformed into glucuronide
      conjugates and unconjugated trihydroxy derivatives; it was also secreted in part
      in unchanged form. In the rat, 7% was secreted in unconjugated trihydroxy
      derivatives and 3% in unchanged form; in the hamster, 7% was secreted as
      unconjugated trihydroxy derivatives and 4% in unchanged form. The secreted bile
      acid species that showed the highest correlation with bile flow by far was always
      the unconjugated form in both rat and hamster. By multiple regression analysis,
      the apparent choleretic activity (microliters of induced bile flow per micromoles
      recovered bile acid molecules) indicated marked hypercholeresis for the
      unconjugated bile acid marked hypercholeresis for the unconjugated bile acid with
      values ranging from 100 to 300 microliters/mumol. Bile flow also correlated with
      total bile acid recovery for ursodeoxycholate in rat and norursodeoxycholate in
      hamster, but in all studies the apparent choleretic activity was far lower. Other
      calculations indicated that most bile flow during the first 30 min was induced by
      secretion of the unconjugated bile acid species in all experiments, the
      proportion ranging from 50% to 90%. The results indicate that when a bolus of
      ursodeoxycholate or norursodeoxycholate is presented to the perfused rodent
      liver, the secretion of the unchanged bile acid appears to be responsible for
      most of the bile flow, probably by a cholehepatic shunting mechanism.

PMID- 1999324
TI  - Regulation of collagen production in freshly isolated cell populations from
      normal and cirrhotic rat liver: effect of lactate.
AB  - Previous work has shown that lactic acid, and to a lesser extent pyruvic acid, is
      able to increase collagen synthesis significantly in liver slices of CCl4-treated
      rats but not normal rats. The purpose of this report is to document which cells
      in the cirrhotic liver are responsible for the lactate-stimulated increase in
      collagen synthesis. It was found that (a) incorporation of 3H-proline into
      protein-bound 3H-hydroxyproline is increased threefold to fourfold in hepatocytes
      from CCl4-treated rats as compared with normal rat hepatocytes; (b) neither the
      hepatocytes from normal nor those from CCl4-treated rats modify their collagen
      synthesizing capacity when 30 mmol/L lactic acid was added to the incubation
      medium; (c) nonparenchymal cells obtained from livers of CCl4-treated rats
      synthesize much less collagen than hepatocytes, but their synthesis is stimulated
      twofold by lactic acid; (d) from the different nonparenchymal cells, only fat
      storing (Ito) cells increase collagen synthesis when lactic acid is present in
      the incubation medium. These results suggest that the increased lactic acid
      levels observed in patients with alcoholic hepatic cirrhosis may play an
      important role in the development of fibrosis by stimulating collagen production
      by fat-storing (Ito) cells.

PMID- 1999325
TI  - Fish oil protects mice against acetaminophen hepatotoxicity in vivo.
AB  - Recent observations suggest that products of non-parenchymal liver cells such as
      eicosanoids and cytokines might play a role in the expression of liver injury
      after administration of acetaminophen and other noxious agents. We therefore
      investigated the effect of a fish oil diet, which results in the generation of
      eicosanoids with altered biological properties and suppresses the production of
      certain cytokines on acetaminophen hepatotoxicity. Mice were fed a diet with
      either 20% fish oil containing n-3 fatty acids or 20% olive oil containing n-6
      fatty acids for 2 wk. Cytochrome P-450 activity and the concentration of
      glutathione were similar in the two groups before acetaminophen administration.
      Nevertheless, 24 hr after the administration of 375 mg/kg acetaminophen
      intraperitoneally, the extent of centrilobular necrosis and the activity of ALT
      in plasma were significantly lower in the n-3 fatty acid group (median = 277 vs.
      3,367 IU/L; p less than 0.001). In the n-3 fatty acid group covalent binding of
      the drug to liver proteins (0.19 +/- 0.03 vs. 0.67 +/- 0.07 nmol/mg protein; p
      less than 0.01) and the median plasma concentration of acetaminophen (0.1 vs. 0.6
      mmol/L) were significantly lower 3 hr after dosing. Mice fed the n-3 fatty acid
      diet excreted less acetaminophen sulfate but significantly more acetaminophen
      glucuronide in 24 hr. Thus the major protective effect of the fish oil diet
      appears to be an increased clearance of acetaminophen resulting from a
      stimulation of the glucuronidation of acetaminophen, which may be due to the
      fluidization of microsomal membranes by fish oil.

PMID- 1999326
TI  - A new method to monitor Kupffer cell phagocytosis continuously in perfused rat
      liver.
AB  - A new method was developed to monitor Kupffer cell phagocytosis continuously in
      perfused liver using a fluorescent probe, rhodamine-gelatin, synthesized from
      gelatin and rhodamine isothiocyanate. In perfused rat liver, phagocytosis by
      Kupffer cells was assessed both by uptake of the dye and from fluorescence
      measured from the liver surface. Uptake of rhodamine-gelatin and surface
      fluorescence (520----585 nm) increased as perfusate concentrations of rhodamine
      gelatin were elevated. Histological examination revealed that fluorescence caused
      by rhodamine-gelatin was concentrated in cells lining the sinusoid. Furthermore,
      when hepatic parenchymal, endothelial and Kupffer cells were isolated by
      centrifugal elutriation after pretreatment in vivo with rhodamine-gelatin, the
      fluorescent label was detected nearly exclusively in the Kupffer cell fraction.
      Fluorescence of rhodamine-gelatin from the liver surface was directly
      proportional to uptake of rhodamine-gelatin, indicating that measurement of
      surface fluorescence could be used as an index of phagocytic activity of Kupffer
      cells. Uptake of rhodamine-gelatin and fluorescent labeling of sinusoidal cells
      were inhibited nearly completely by dextran sulfate, which decreases phagocytic
      activity, and were increased by about 50% by pretreatment with endotoxin, which
      stimulates phagocytosis. This new method was combined with standard procedures to
      monitor parenchymal cell function (e.g., oxygen uptake and release of lactate
      dehydrogenase), Kupffer cell phagocytic activity and parenchymal cell injury
      simultaneously during perfusion with the hepatotoxicant allyl alcohol. Activation
      of phagocytosis by Kupffer cells monitored by rhodamine-gelatin fluorescence
      occurred within 5 min of addition of allyl alcohol. On the other hand,
      parenchymal cell injury, assessed from release of lactate dehydrogenase, did not
      begin until 40 min and reached maximal values at around 90 min.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1999327
TI  - Trolox protects rat hepatocytes against oxyradical damage and the ischemic rat
      liver from reperfusion injury.
AB  - Trolox, a hydrophilic analog of vitamin E, was reported to scavenge peroxyl
      radicals from artificial systems better than its parent compound. Here we
      examined the possible cytoprotective effect of Trolox in cultured hepatocytes and
      in the rat liver. In cultured rat hepatocytes, 0.5 to 16 mmol/L Trolox (with
      optimum between 1 to 2 mmol/L) was observed to prolong the survival of cells
      exposed to oxyradicals generated with xanthine oxidase-hypoxanthine. The
      protection by 1 mmol/L Trolox surpassed that provided by either ascorbate,
      mannitol, superoxide dismutase and/or catalase--each at a level giving its
      maximal protection in the same system. In both a global and partial model of
      hepatic ischemia-reperfusion in rats, infusion of Trolox (7.5 to 10 mumol/kg body
      weight) just before reflow reduced by greater than 80% the liver necrosis
      sustained in untreated (no Trolox) control rats. Such organ salvage was
      apparently accompanied by approximately 50% reduction in the amount of hepatic
      conjugated dienes, which were quantified by a highly specific radiochemical
      assay. Since conjugated dienes are presumed to be good "markers" of oxyradical
      damage, our data may have provided a semiquantitative link between free radical
      induced necrosis and its chemical imprint in vivo. The data also indicated a
      relatively rapid and potent antioxidant-like action by Trolox on rat hepatocytes
      and on the postischemic reperfused rat liver.

PMID- 1999329
TI  - Brown pigment gallstones: the role of bacterial hydrolases and another missed
      opportunity.

PMID- 1999328
TI  - Temporal relationship between the decrease in arterial pressure and sodium
      retention in conscious spontaneously hypertensive rats with carbon tetrachloride
      induced cirrhosis.
AB  - It has been proposed that the initial event of sodium retention in cirrhosis is a
      peripheral arteriolar vasodilation causing underfilling of the arterial vascular
      compartment and stimulation of the renin-aldosterone and sympathetic nervous
      systems. To test this hypothesis, systolic blood pressure, sodium balance and
      urinary excretion of sodium and aldosterone were sequentially measured in 13
      conscious spontaneously hypertensive rats submitted to a cirrhosis induction
      program with carbon tetrachloride and phenobarbital and in 14 control
      hypertensive animals. No significant differences were found between control and
      cirrhotic rats in any of the measured parameters during the first 7 wk of the
      study. The eighth week sodium retention developed in cirrhotic rats as indicated
      by a positive sodium balance and a marked decrease of sodium excretion. At the
      same time a significant reduction in systolic blood pressure and a great increase
      in urinary excretion of aldosterone were detected. These changes were more marked
      the ninth week of the study. In cirrhotic rats there was a highly significant
      direct correlation between systolic blood pressure and urinary sodium excretion.
      Postmortem examination showed a histological picture of cirrhosis in all animals
      given carbon tetrachloride and ascites in six of them. These results indicate
      that the onset of hyperaldosteronism and sodium retention in conscious
      spontaneously hypertensive rats with carbon tetrachloride-induced cirrhosis is
      chronologically related to a significant decrease in arterial pressure, thus
      supporting the "peripheral arterial vasodilation hypothesis" of ascites.

PMID- 1999330
TI  - Lichen planus and the liver.

PMID- 1999331
TI  - How does endoscopic sclerotherapy alter splanchnic hemodynamics?

PMID- 1999332
TI  - Primary biliary cirrhosis.

PMID- 1999333
TI  - Resistance calculation and expression.

PMID- 1999334
TI  - Acatalasemia.
AB  - The abnormalities in acatalasemia at the gene level as well as properties of the
      residual catalase in Japanese acatalasemia are historically reviewed. The
      replacement of the fifth nucleic acid, guanine, in the fourth intron by adenine
      in the acatalasemic gene causes a splicing mutation and hence a deficiency of
      mRNA. The guanine-to-adenine substitution was detected in two Japanese
      acatalasemic cases from different families. The properties of the residual
      catalase are similar to those of normal catalase; the exons are identical. The
      properties of the residual catalase and the molecular defect in the catalase gene
      are compared among Japanese, Swiss, and mouse acatalasemias. The physiological
      role of catalase, as judged from human acatalasemic blood and acatalasemic mice,
      is also described.

PMID- 1999335
TI  - Selection of DNA sequences from interval 6 of the human Y chromosome with
      homology to a Y chromosomal fertility gene sequence of Drosophila hydei.
AB  - An experimental approach towards the molecular analysis of the male fertility
      function, located in interval 6 of the human Y chromosome, is presented. This
      approach is not based on the knowledge of any gene product but on the assumption
      that the functional DNA structure of male fertility genes, evolutionary conserved
      with their position on the Y chromosome, may contain an evolutionary conserved
      frame structure or at least conserved sequence elements. We tested this
      hypothesis by using dhMiF1, a fertility gene sequence of the Y chromosome of
      Drosophila hydei, as a screening probe on a pool of cloned human Y-DNA sequences.
      We were able to select 10 human Y-DNA sequences of which 7 could be mapped to Y
      interval 6 (the pY6H sequence family). Since the only fertility gene of the human
      Y chromosome is mapped to the same Y interval, our working hypothesis seems to be
      strongly supported. Most interesting in this respect is the isolation of the Y
      specific repetitive pY6H65 sequence. The pY6H65 locus extends to a length of at
      least 300 kb in Y interval 6 and has a locus-specific repetitive sequence
      organization, reminiscent of the functional DNA structure of Y chromosomal
      fertility genes of Drosophila. We identified the simple sequence family (CA)n as
      one sequence element conserved between the Drosophila dhMiFi fertility gene
      sequence and the homologous human Y-DNA sequences.

PMID- 1999336
TI  - Chromosome assignment of four RAS-related RAB genes.
AB  - The human RAB genes share structural and biochemical properties with the RAS gene
      superfamily. The encoded RAB proteins show 38 to 75% amino acid identity with the
      yeast YPT1 and SEC4 gene products. We used four human RAB-cDNAs, RAB3B, RAB4,
      RAB5 and RAB6, to map the corresponding genes on human chromosomes. These genes
      were assigned to 1p32-p31, 1q42-q43, 3p24-p22 and 2q14-q21, respectively, by in
      situ hybridization.

PMID- 1999337
TI  - Duplication of exons 13, 14 and 15 of the LDL-receptor gene in a patient with
      heterozygous familial hypercholesterolemia.
AB  - During a survey of Italian patients with familial hypercholesterolemia (FH), we
      identified an FH heterozygous patient with a gross rearrangement of the low
      density lipoprotein (LDL) receptor gene. Southern blot analysis of the proband's
      DNA digested with restriction enzymes PvuII, BamHI, BglII and XbaI and
      hybridization with cDNA probes complementary to the 3' end of the gene revealed
      the presence of abnormal fragments that were approximately 7 kb larger than their
      normal counterparts. DNA digestion with other enzymes (EcoRV, NcoI, KpnI and
      StuI) and hybridization with probes complementary to exons 13-17 generated normal
      fragments and an abnormal fragment of 6.3-6.8 kb. These results are consistent
      with the presence of an insertion of approximately 7 kb caused by a duplication
      of exons 13, 14 and 15. This is a novel mutation that is most probably the result
      of an unequal crossing-over between repetitive sequences located in intron 12 and
      intron 15. This novel mutation has been designated FHBologna 2.

PMID- 1999338
TI  - Characterization of a frequent polymorphism in the coding sequence of the Tp53
      gene in colonic cancer patients and a control population.
AB  - We describe a simple method for characterizing a frequent polymorphism (that
      substitutes an arginine for a proline) in the coding sequence of the Tp53 gene in
      patients with colonic cancer and in a control population. We could find no
      evidence that this polymorphism is associated with a marked predisposition to
      colorectal cancer.

PMID- 1999339
TI  - Some Mexican glucose-6-phosphate dehydrogenase variants revisited.
AB  - Glucose-6-phosphate dehydrogenase (G6PD) deficiency appears to be fairly common
      in Mexico. We have now examined the DNA of three previously reported
      electrophoretically fast Mexican G6PD variants, -G6PD Distrito Federal, G6PD
      Tepic, and G6PD Castilla. All three of these variants, believed on the basis of
      biochemical characterization and population origin to be unique, have the G----A
      transition at nucleotide 202 and the A----G transition at nucleotide 376,
      mutations that we now recognize to be characteristic of G6PD A-. Two other
      Mexican males with G6PD deficiency were found to have the same mutation. All five
      have the (NlaIII/FokI/PvuII/PstI) haplotype characteristic of G6PD A -in Africa.
      Since the PvuII+ genotype seems to be rare in Europe, we conclude that all of
      these G6PD A - genes had their ancient origin in Africa, although in many of the
      Mexican patients with G6PD A -202A/376G the gene may have been imported more
      recently from Spain, where this variant, formerly known as G6PD Betica, is also
      prevalent.

PMID- 1999340
TI  - Predivision in human oocytes at meiosis I: a mechanism for trisomy formation in
      man.
AB  - Cytogenetic preparations from oocytes remaining unfertilised after in vitro
      fertilisation revealed single chromatids (as opposed to whole chromosomes) in 4
      out of 38 meiosis II metaphases. In one oocyte, a single chromatid was present in
      addition to the normal 23,X complement, and in three oocytes, two identical but
      separate chromatids replaced one whole chromosome within the complement. The data
      indicate that the chromatids have arisen as a result of premature division of the
      centromeres at meiosis I ("predivision"). None of the oocytes were hyperhaploid
      with an extra whole chromosome. These findings are at variance with the general
      belief that trisomy in man is largely a consequence of nondisjunction of whole
      bivalents at meiosis I and they suggest that predivision resulting in separate
      chromatids may be a significant mechanism for human trisomy.

PMID- 1999341
TI  - Mapping the gene encoding the human erythroid transcriptional factor NFE1-GF1 to
      Xp11.23.
AB  - The X-linked NFE1 gene encodes an erythroid factor involved in globin gene
      transcription. Using a human cDNA clone encoding this factor, we show, by in situ
      hybridization and by analysis of human-rodent hybrid cell lines, that this gene
      is located in Xp11.23. In the absence of polymorphisms in the NFE1 gene, these
      results allow the study of the possible relationships between NFE1 mutations and
      X-linked hereditary persistence of fetal hemoglobin by linkage analysis with RFLP
      markers of the region. A female patient, hemizygous for the NFE1 locus, shows
      essentially normal hematological parameters.

PMID- 1999342
TI  - Identification of a cystic fibrosis mutation: deletion of isoleucine506.
AB  - The recent isolation of the cystic fibrosis (CF) gene has resulted in the
      identification of a common mutation (delta F508) that is found on about 70% of CF
      chromosomes and that comprises a deletion of 3 bp and results in the omission of
      Phe508 from within a putative ATP-binding domain of the predicted gene product.
      We describe a CF mutation that involves the deletion of 3 bp encoding Ile506 or
      Ile507. This is a rare mutation found in less than 1% of CF chromosomes and could
      be mistaken for delta F508 using the current methods for the molecular diagnosis
      of CF.

PMID- 1999343
TI  - No evidence for sequences structurally related to the RB1 gene in the human
      genome.
AB  - The retinoblastoma (RB1) gene is a ubiquitously expressed gene encoding a cell
      cycle control protein. Inactivation of this gene plays a crucial role in the
      development of retinoblastoma, osteosarcoma, and other tumors. In a search for
      structurally related gene sequences we identified a 5.5-kb BamHI fragment
      strongly cross-hybridizing with the 5' end of the RB1 cDNA. Molecular cloning, in
      situ hybridization, restriction mapping, and sequence analysis identified this
      DNA segment as the 28S rRNA gene. The absence of other cross-hybridizing
      sequences suggests that the RB1 gene is not part of a structurally related gene
      family.

PMID- 1999344
TI  - Incidence of Menkes disease.
AB  - We have calculated the incidence of Menkes disease for Denmark, France, The
      Netherlands, the United Kingdom and West Germany, based on known Menkes patients
      born during the time period 1976-87. Considering live-born Menkes patients, the
      combined incidence for these five countries is 1 Menkes patient per 298,000 live
      born babies. If the number of affected aborted fetuses are taken into account,
      the incidence is 1 Menkes per 254,000 live-born babies. This incidence, which is
      2-4 times lower than earlier published incidence figures, places Menkes disease
      as an extremely rare disease. The mutation rate for Menkes disease is estimated
      to be 1.96 x 10(-6), based on the number of isolated Menkes cases born during the
      time period 1976-87 and the total number of newborn males during this time.

PMID- 1999345
TI  - Characterisation of a Xp21 microdeletion syndrome in a 2-year-old boy with
      muscular dystrophy, glycerol kinase deficiency and adrenal hypoplasia congenita.
AB  - We report a 2-year-old boy with Duchenne muscular dystrophy (DMD), glycerol
      kinase deficiency (GK) and adrenal hypoplasia congenita (AHC). At three weeks of
      age, the patient was hospitalized for the first time with symptoms of hypotone
      dehydration because of AHC. At present, he shows severe muscular hypotonia and
      developmental delay. The patient and his family were referred to us for prenatal
      diagnosis and carrier testing in the mother of the patient and the mother's
      sister, respectively. The patient's DNA was examined by Southern blot and
      polymerase chain reaction analyses, using cDNA and genomic probes within and
      around the dystrophin (DYS) locus. A deletion was revealed, spanning DXS28, the
      whole dystrophin locus, DXS84 and DXS148, whereas DXS67, DXS68 (pter) and OTC
      (cen) were found to be retained. The cytogenetically visible microdeletion was
      also seen in the patient's mother, but not in the mother's sister or the
      patient's maternal grandmother. Our findings support the locus order pter-DXS67
      DXS68-DXS28-AHC-GK-DMD-cen.

PMID- 1999346
TI  - Homozygous condition for a BrdU-requiring fragile site on chromosome 12.
AB  - A rare BrdU-sensitive fragile site, designated FRA12C*RQ24.2 has a relatively
      high frequency in the normal population. It can be demonstrated in a heterozygous
      and homozygous condition. There is no evidence that a phenotypic abnormality is
      associated with the expression of this site. A comparison with the fragile site
      FRA10B*RQ25.2 has revealed common features with FRA12C*RQ24.2.

PMID- 1999347
TI  - Physical mapping of two Xp markers DXS16 and DXS143.
AB  - Lymphocyte karyotyping of an infant girl with the clinical features of
      microphthalmia, iridoschisis, goiter, hip joint dysplasia, labium synechia and
      craniotabes revealed an Xp deletion. The lymphocyte karyotypes of the parents
      were normal. Bromodeoxyuridine incorporation studies showed that, in 42 out of 43
      metaphases, the deleted X chromosome was late replicating. In one metaphase, the
      normal X chromosome was observed to be allocyclic. Using DNA markers from the
      Xp22 region, the breakpoint was assigned distal to DXS16 (pXUT23) and proximal to
      DXS143 (dic56). Dosage intensity measurements confirmed that the STS gene and the
      DNA marker DXS31 were involved in the deleted area. Restriction fragment length
      polymorphism analysis revealed that the paternally derived X-chromosome was
      deleted.

PMID- 1999348
TI  - De novo complex chromosomal rearrangement in a woman with recurrent spontaneous
      abortion and one healthy daughter.
AB  - Although rare, complex chromosomal rearrangements have been reported in the
      literature. The result is multiple congenital malformations in the offspring and
      recurrent spontaneous abortion. Chromosome 7 is usually involved, but in our
      patient chromosome 18 was involved.

PMID- 1999349
TI  - A novel MHC class I-related molecule expressed on mouse thymic stroma cells and
      mature lymphocytes.
AB  - A monoclonal antibody (mAb) TP-3 has been established by immunizing rats with the
      BALB/c mouse thymic epithelial cell line TEL-2. The TP-3 antigen is expressed on
      stroma cells of thymus, spleen, and lymph node in syngeneic BALB/c mice (H-2d).
      This antigen is also expressed at a low level on the cell surface of immature
      thymocytes, and at a high level on mature T and B cells. In allogeneic mice such
      as C57BL/6 (H-2b) or C3H (H-2k), no cells expressed the TP-3 antigen. Using H-2
      congenic mice, reactivity with mAb TP-3 was found to map to a region of H-2DdLd
      or between Dd and Qa, suggesting that TP-3 is a major histocompatibility complex
      (MHC) class I antigen. However, immunoprecipitation analysis indicated that this
      antigen is not identical to the classical mouse class I molecules in terms of
      molecular size, antigenicity, and tissue distribution.

PMID- 1999350
TI  - The human leucocyte antigen CD48 (MEM-102) is closely related to the activation
      marker Blast-1.
AB  - The glycosyl phosphatidylinositol (GPI)-linked antigen recognized by monoclonal
      antibody (mAb) MEM-102 is expressed on all peripheral blood lymphocytes, both
      resting and activated. Its properties are very similar to a previously described
      activation antigen, Blast-1. The amino acid sequence deduced from the structure
      of cloned cDNA is identical to that of the Blast-1 antigen except for a single
      amino acid residue. There are several other minor differences in the nucleotide
      sequence of the Blast-1 and MEM-102 cDNAs that do not affect the predicted
      structure of the polypeptide product. The amino acid sequence of the first 15 N
      terminal residues of the antigen purified from Raji cells is found in the deduced
      sequence close to the presumed boundary between the leader peptide and mature
      polypeptide. Properties of the recombinant product expressed in COS cells are
      similar to the antigen isolated from peripheral blood mononuclear cells (PBMNCs)
      or B-and T-cells lines. The antigen purified on immobilized mAb MEM-102 is
      recognized by all six known CD48 mAbs under western blotting conditions. COS
      cells transfected with MEM-102 cDNA react with all the CD48 mAbs. It is concluded
      that mAb MEM-102 is directed against the as yet poorly characterized antigen
      CD48, which is therefore structurally closely related to Blast-1. Several
      possibilities are discussed that might account for the apparent discrepancy
      between the broad pan-leucocyte expression of the between the broad pan-leucocyte
      expression of the MEM-102/CD48 antigen and much more restricted expression of the
      epitope recognized by the previously described mAb defining the Blast-1 antigen.

PMID- 1999351
TI  - The isolation of cDNA clones for CD48.
AB  - HuLy-m3 is an Mr 47,000 pan-leukocyte antigen detected by the monoclonal antibody
      (mAb) 5-4.8. This report describes the isolation and analysis of a cDNA clone
      encoding HuLy-m3. Serological analysis demonstrated that antibodies of the CD48
      cluster also reacted with transfected cells expressing HuLy-m3. The DNA sequence
      of the clone suggests linkage to the cell membrane through a glycosyl
      phosphatidylinositol tail and this was verified experimentally. Sequence
      similarity with the human B-cell activation antigen Blast-1 was noted.

PMID- 1999352
TI  - An unusual form of alternative splicing in the HLA-DNA gene.
AB  - The HLA-DNA gene of the human major histocompatibility complex (MHC) produces RNA
      transcripts of unusual size compared to the 1.3 kilobase (kb) transcripts of
      other class II genes. Several cDNA clones derived from HLA-DNA transcripts were
      isolated, including a full-length 3.5 kb cDNA named DN1. Sequence analysis of DN1
      demonstrated that the 3.5 kb transcript is fully spliced, contains a long 3'
      untranslated region, and encodes an apparently normal class II alpha chain. Two
      other cDNA clones, DN2 and DN7, revealed an alternative splice that resulted from
      the use of a splice acceptor upstream of the second exon encoding the alpha 1
      domain. The translation product of this alternative transcript would share the
      signal sequence of the DN alpha chain but would otherwise be unrelated. Removal
      of the signal sequence would yield a highly basic peptide of 42 amino acids. RNA
      was prepared by in vitro transcription of DN1 and DN2, and was used to direct
      protein synthesis in a rabbit reticulocyte system. The product of DN1 had an
      apparent relative mass of 25,000, whereas the product of DN2 was a peptide with a
      relative mass of about 6000. The alternatively spliced RNA represents about 1/10
      of the transcripts from the HLA-DNA gene in the cells tested, which included
      transformed B-cell lines as well as normal blood cells and thymus cells.

PMID- 1999353
TI  - Sequencing of HLA-D in responders and nonresponders to short ragweed allergen,
      Amb a V.
AB  - We investigated the molecular basis for the striking association between HLA
      DR2,Dw2 and human immune responsiveness to the Ambrosia artemisiifolia (short
      ragweed) pollen allergen Amb a V by sequencing the second exons of the DRB and
      DQB1 genes of 17 selected ragweed-allergic Caucasoid subjects. We also studied
      the DQA1 allelic polymorphic regions (APRs) in these patients by dot-blotting
      using sequence-specific oligonucleotides (SSOs). The deduced amino acid sequences
      of the respective class II beta and alpha polypeptides were compared, with
      particular emphasis on residues in the APRs that are implicated in antigen
      binding. No evidence for "new" HLA-DRB or DQB sequences unique to Amb a V
      responders were found on sequencing seven Dw2+ subjects. This suggests that the
      presence of a particular Dw2-associated class II molecule usually provides a
      necessary, but not always sufficient condition for responsiveness to Amb a V. The
      HLA phenotypes of three subjects suggest that they possess novel recombinant
      haplotypes containing either DRB1*1501 and DRB5*0101 (DR2.2-associated) or
      DQB1*0602 (DQ1.2-associated) sequences. In these subjects, responsiveness to Amb
      a V was associated with the DR2.2 but not the DQ1.2 sequences, suggesting that DR
      alpha beta I or DR alpha beta V class II molecules are involved in antigen
      presentation. We investigated whether there may be shared HLA-D-encoded responder
      sequences present in all responders, including some exceptional DR2- Amb a V
      responders. The 13 subjects producing antibody (Ab) responses to Amb a V [either
      from natural exposure and/or after ragweed immunotherapy (Rx)] possessed
      DRB1*1501, 1601, 1602, 0103, 0402, 0404, 0801, or 1101 sequences, which share the
      majority of their aa residues in the APRs 2-4. Some of these shared residues
      might be important for the binding of a common Amb a V agretope prior to
      presentation of the class II Amb a V complex to the T-cell receptor (Tcr). An
      alternative postulate is that the recognition of two different Amb a V agretopes
      may be determined by the beta 1 polypeptides of molecules having the DR2 and DQw3
      specificities.

PMID- 1999354
TI  - Rearrangement patterns of T-cell receptor genes in the spleen of athymic (nu/nu)
      young mice.
AB  - Although the athymic nude mouse is grossly deficient in peripheral T cells, the
      number of lymphocytes bearing T-cell markers (L3T4, LyT2) and the alpha beta or
      gamma delta T-cell receptor (Tcr) increases steadily with age. The anatomical
      site(s) where these cells arise are unknown. Splenocytes from 3-5-week-old
      C57BL/6 (nu/nu) mice contain 2%-5% Pro-T cell progenitors identified with the
      Joro 37-5 and Joro 75 antibodies, but not mature T cells. To study Tcr gene
      rearrangement outside the thymus, we fused splenocytes from 3-5-week-old C57BL/6
      nude mice with the T-cell lymphoma BW 100.129. Of 22 hybrids that grew stably in
      culture, four had Tcrd-VD1-D2-J1, two had Tcrd-VD2-J1, and seven had Tcrd-D1-D2
      types of rearrangement. Eight hybrids had rearranged the Tcrg-2 gene cluster, but
      none had rearranged Tcrg-1, -3, or -4. None of the hybrids had rearranged the
      Tcrb gene cluster and 13 contained DJ rearrangements at the Igh locus. We
      conclude that the spleen is one of the extrathymic sites where T-cell progenitors
      can rearranged Tcrd and Tcrg genes. However, there was no evidence for Tcrb gene
      rearrangements in this organ. Furthermore, the analysis of this limited number of
      hybrids suggests that extrathymic Tcr gene rearrangements seem to be distinct and
      much less diverse than those found in the developing thymocytes.

PMID- 1999355
TI  - Additional mapping of mouse chromosome 2 genes.
AB  - The purpose of this work was to elucidate the genetic fine structure of the
      central portion of mouse chromosome (Chr) 2. Seven Chr 2 congenic mouse strains
      [B10.PA(L)-pa we un at, B10.PA(L)-pa Aw, B10.PA(L)-we un at, B10.PA(J)-pa a,
      B10.FS-we Aw, B10.C-we Aw, and B10.YBR-a] were produced. Breeding studies were
      carried out using strains B10.PA(L)-pa we un at and B10.LP-H-13b to accurately
      determine the recombination frequencies between marker genes pa and we (1.9% +/-
      0.3), we and un (8.8% +/- 0.5), and un and at (4.5% +/- 0.4) of strain B10.PA(L)
      pa we un at. These strains and other Chr 2 congenic strains were typed for
      immunologically defined loci using monoclonal antibody (mAb) C23 reactive with
      the gene product of B2mb T-lymphocyte clone C1 reactive with the gene product of
      H-3a and H-3c, and lymphocyte clone H1.8 reactive with the gene product of Hd-1a.
      B2m and H-3 typing located a recombinational event separating [pa B2m H-3] from
      we (the order of bracketed genes is not known). Hd-1 typing indicated that Hd-1
      maps distal to [H-42, H-44] and proximal to un. The gene order [pa, B2m, H-3],
      we, [H-42, H-45], Hd-1, un, H-13, at, with H-44 mapping centromeric to Hd-1, is
      indicated by the data.

PMID- 1999356
TI  - Molecular biology of angiotensinogen.

PMID- 1999357
TI  - Significance of vascular renin for local generation of angiotensins.
AB  - The effects of specific renin inhibitors, angiotensin converting enzyme
      inhibitors, indomethacin, and prostaglandin I2 analogue on the release of
      angiotensins from isolated and Krebs-Ringer-perfused rabbit mesenteric arteries
      were examined. Three different renin inhibitors suppressed release of
      angiotensins in dose-dependent manners. At the highest concentration (10(-7) M),
      the inhibitors EMD 52,620, EMD 54,388, and EMD 52,742 induced 46%, 52%, and 48%
      decreases, respectively, in the basal rate of immunoreactive angiotensin II
      release. These results provide clear evidence that released angiotensins are
      produced by the specific action of vascular renin and that the renin inhibitors
      suppress the vascular renin-angiotensin system as well as the circulating renin
      angiotensin system and appear to provide a useful mode for the treatment of
      hypertension. Nonsulfhydryl angiotensin converting enzyme inhibitors cilazapril
      and delapril were more effective than captopril, and ramipril was equipotent to
      captopril, suggesting that the effectiveness of angiotensin converting enzyme
      inhibitors on the vascular renin-angiotensin system cannot be explained only by
      its inhibitory effect on angiotensin converting enzyme. Indomethacin, which was
      reported to suppress angiotensin II release from rat hind limbs, elicited a dose
      dependent increase of angiotensin release from rabbit mesenteric arteries. These
      results suggest that a difference exists in the regulatory mechanisms in the
      release of angiotensins from diverse vascular beds.

PMID- 1999358
TI  - Preservation of renal function by angiotensin during chronic adrenergic
      stimulation.
AB  - The purpose of the present study was to determine the role of angiotensin II (Ang
      II) in mediating renal responses to chronic intrarenal norepinephrine infusion.
      Norepinephrine was continuously infused for 5 days into the renal artery of
      unilaterally nephrectomized dogs at progressively higher daily infusion rates:
      0.05, 0.10, 0.20, 0.30, and 0.40 micrograms/kg/min. In three additional groups of
      dogs, norepinephrine infusion was repeated during chronic intravenous captopril
      administration to fix plasma Ang II concentration at 1) low levels (no Ang II
      infused), 2) high levels in the renal circulation (Ang II infused intrarenally at
      a rate of 1 ng/kg/min), and 3) high levels in the systemic circulation (Ang II
      infused intravenously at a rate of 5 ng/kg/min). In the control group of animals
      with intact renin-angiotensin systems, there were progressive increments in mean
      arterial pressure (from 96 +/- 4 to 141 +/- 6 mm Hg) and plasma renin activity
      (from 0.4 +/- 0.1 to 10.9 +/- 4.5 ng angiotensin I/ml/hr) and concomitant
      reductions in glomerular filtration rate and renal plasma flow to approximately
      40% of control during the 5-day norepinephrine infusion period. In marked
      contrast, when captopril was infused chronically without Ang II, mean arterial
      pressure was 20-25 mm Hg less than that under control conditions, and the renal
      hemodynamic effects of norepinephrine were greatly exaggerated; by day 3 of
      norepinephrine infusion, both glomerular filtration rate (16 +/- 2% of control)
      and renal plasma flow (12 +/- 4% of control) were considerably lower than values
      in control animals (86 +/- 4% and 80 +/- 8% of control, respectively). Similarly,
      when a high level of Ang II was localized in the renal circulation during
      captopril administration, mean arterial pressure was depressed, and again there
      were pronounced renal responses to norepinephrine. Conversely, when Ang II was
      infused intravenously during captopril administration, mean arterial pressure was
      not reduced, and the glomerular filtration rate and renal plasma flow responses
      to norepinephrine were similar to those that occurred under control conditions.
      These findings indicate that the renin-angiotensin system prevents exaggerated
      renal vascular responses to chronic norepinephrine stimulation by preserving
      renal perfusion pressure.

PMID- 1999359
TI  - Renal hemodynamic effects of calcium antagonists in rats with reduced renal mass.
AB  - The intrarenal hemodynamic effects of antihypertensive agents vary considerably,
      and these microcirculatory effects may contribute to long-term structural
      sequelae in the setting of chronic renal disease. To investigate the consequences
      of blood pressure reduction with calcium antagonists, 5/6 nephrectomized Munich
      Wistar rats underwent baseline determinations of mean arterial pressure, whole
      kidney function, and single nephron glomerular filtration rate, after which
      intravenous infusions of verapamil or diltiazem were given in doses that acutely
      normalized blood pressure; control rats received saline vehicle. During the
      baseline period, all rats exhibited comparably elevated values for mean arterial
      pressure and single nephron glomerular filtration rate. During the experimental
      infusion, control rats exhibited continued single nephron hyperfiltration (84 +/-
      8 nl/min) as a result of elevations in both glomerular capillary plasma flow rate
      (330 +/- 36 nl/min) and glomerular capillary hydraulic pressure (68 +/- 3 mm Hg),
      whereas the glomerular capillary ultrafiltration coefficient was low [0.050 +/-
      0.009 nl/(sec.mm Hg)]. Both verapamil (148 +/- 6 to 103 +/- 3 mm Hg, p less than
      0.05) and diltiazem (154 +/- 6 to 102 +/- 2 mm Hg, p less than 0.05) normalized
      arterial pressure, which did not change in control rats (150 +/- 7 to 142 +/- 8
      mm Hg). Single nephron hyperfiltration and hyperperfusion were comparable among
      groups during the experimental period; compared with baseline values, diltiazem
      (97 +/- 8 to 71 +/- 7 nl/min, p less than 0.05) but not verapamil (90 +/- 7 to 83
      +/- 6 nl/min, p = NS) modestly lowered the single nephron glomerular filtration
      rate.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1999361
TI  - Calcium and prostaglandin E2 in renomedullary interstitial cells.
AB  - Renomedullary interstitial cells cultured from the Dahl salt-resistant rat have
      higher levels of basal cytosolic calcium and prostaglandin E2 and are more
      responsive to vasopressin than interstitial cells from the Dahl salt-sensitive
      rat. We examined the potential role of inositol phospholipid hydrolysis in
      mediating these differences. Vasopressin-induced increases in labeled inositol
      phosphates were enhanced in renomedullary interstitial cells from Dahl salt
      resistant compared with those from salt-sensitive rats. Addition of neomycin
      reduced basal production of labeled inositol phosphates and abolished the
      increase in inositol phosphates induced by vasopressin. Neomycin also prevented
      the peak decline pattern in cytosolic Ca2+ seen with vasopressin but did not
      influence basal cytosolic Ca2+. In the presence of neomycin, vasopressin induced
      a modest but prolonged increase in cytosolic calcium. In contrast to its marked
      effects on inositol phosphate production, neomycin was without effect on basal or
      vasopressin-responsive prostaglandin E2 production. Moreover, basal and
      vasopressin-induced increases in cytosolic Ca2+ remained higher in renomedullary
      interstitial cells from Dahl salt-resistant versus those from salt-sensitive rats
      exposed to neomycin. The results do not support a requirement for phospholipase C
      induced inositol phospholipid hydrolysis in the mediation of vasopressin actions
      on prostaglandin E2 production by renomedullary interstitial cells and imply that
      the differences in cytosolic Ca2+ and prostaglandin E2 seen in these two cell
      lines are not related to differences in inositol phospholipid metabolism.

PMID- 1999360
TI  - Adrenergic stimulation of renal prostanoids in the Lyon hypertensive rat.
AB  - Young, genetically hypertensive Lyon (LH) rats exhibited an increased renal in
      vivo turnover of norepinephrine and an elevated urinary excretion of thromboxane
      B2 when compared with normotensive (LN) and low blood pressure (LL) controls.
      Therefore, the effects of norepinephrine (1.2 x 10(-8) to 9.6 x 10(-7) M) and of
      phenylephrine (5 x 10(-8) to 1.9 x 10(-6) M) on renal function and the urinary
      excretion of prostanoids were assessed in isolated perfused kidneys of 8-week-old
      LH, LN, and LL rats. In addition, the effects of norepinephrine were assessed
      before and during thromboxane A2/prostaglandin H2 receptor blockade by AH23848 (4
      x 10(-6) M). Before drug infusion, LH kidneys differed from those of LN and LL
      controls by having an elevated renal vascular resistance and a decreased
      natriuresis and glomerular filtration rate; the urinary output of prostaglandin
      E2 and F2 alpha, of 6-ketoprostaglandin F1 alpha, and of thromboxane B2 was
      similar in the three strains. The constrictor effects of norepinephrine and
      phenylephrine were significantly increased in LH rat kidneys compared with LL but
      not with LN controls, and their pressure-natriuresis was markedly reduced.
      Norepinephrine and phenylephrine induced a 10- to 20-fold dose-dependent increase
      in the synthesis of the four prostanoids, which was more pronounced in LH than in
      LN and LL rats for thromboxane B2 only. AH23848 infusion significantly reduced
      the vascular effects of norepinephrine and increased the natriuretic response of
      LH but not of LN and LL rat kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1999362
TI  - Small artery resistance increases during the development of renal hypertension.
AB  - Vascular pressures were measured in the principal (A1) arteriole and in upstream
      small arteries of the rat cremaster muscle to investigate vascular resistance
      changes associated with one-kidney, one clip Goldblatt hypertension. Pressure
      measurements were made at a proximal and distal site of each vessel using a
      servonull micropipette system. Vessel diameters were measured using video
      microscopy. A1 arteriole and external spermatic artery diameters were both
      decreased after 2 and 4 weeks of hypertension. Mean arterial pressure was
      elevated after 2 weeks of hypertension (106 +/- 4 mm Hg versus 140 +/- 5 mm Hg).
      Likewise, vascular pressures were elevated at every site: pudicepigastric artery
      (36%), external spermatic artery (47%), and A1 arteriole (38%). The pressure drop
      along the external spermatic artery was increased (87%) after 2 weeks of
      hypertension. Mean arterial pressure was further elevated from 2-4 weeks of
      hypertension (105 +/- 4 mm Hg versus 162 +/- 7 mm Hg) but only the proximal pudic
      epigastric artery pressure was further elevated during this time from 2 to 4
      weeks (131 +/- 5 mm Hg versus 147 +/- 7 mm Hg) of hypertension development. This
      was associated with an increased pressure drop (87%) along the artery compared
      with the situation at 2 weeks. These data indicate that small arteries upstream
      from the microcirculation contribute significantly to the increase in vascular
      resistance during hypertension. In addition, these data indicate that the
      increases in small artery resistance do not develop uniformly throughout all
      vessel branches.

PMID- 1999363
TI  - Leukocyte counts and activation in spontaneously hypertensive and normotensive
      rats.
AB  - The etiology for the progressive organ injury in hypertension is largely
      speculative. Recent studies have shown that leukocytes play a key role in several
      cardiovascular diseases. As an initial step toward investigating the role of
      leukocytes in hypertension, we measured leukocyte counts and spontaneous
      activation of granulocytes of freshly drawn unseparated blood samples in
      spontaneously hypertensive rats and in their normotensive counterpart, Wistar
      Kyoto rats. The animals were derived from one breeder in the United States and
      from two breeders in Europe. Total leukocyte counts in young, mature, and old
      hypertensive rats were 50-100% above the controls. The number of granulocytes in
      mature and old spontaneously hypertensive rats in more than 100% elevated
      compared with control rats. In young hypertensive rats the mean granulocyte count
      was only slightly elevated. The number of spontaneously activated granulocytes,
      as detected by the nitroblue tetrazolium reduction, increases with age in both
      species; in mature spontaneously hypertensive rats, it is more than 300% above
      the values in the controls. Furthermore, in mature hypertensive rats the number
      of monocytes, activated monocytes, and the lymphocyte count are also
      significantly elevated over the values in the normotensive controls. It is
      proposed that these elevated leukocyte counts may constitute an enhanced risk for
      organ injury in the spontaneously hypertensive rat.

PMID- 1999364
TI  - Do leukocytes have a role in hypertension?

PMID- 1999365
TI  - Recovery of erythrocyte Na(+)-K(+)-Cl- cotransport activity by enalapril.
AB  - We studied total exchangeable sodium, ion transport activity at maximal rate, and
      erythrocyte Na+ content in response to angiotensin converting enzyme inhibition
      in mild-to-moderate essential hypertensive patients with normal renal function.
      Twenty-five patients (mean age 56 years, range 40-62 years) who had abnormal red
      blood cell Na(+)-K(+)-Cl- cotransport or red blood cell Li(+)-Na+
      countertransport were treated with either enalapril (20 mg daily) or
      hydrochlorothiazide (50 mg daily) during a 30-day period. During the period of
      enalapril treatment, Na(+)-K+ pump and Na(+)-K(+)-Cl- cotransport increased
      significantly from 4,282 +/- 255 to 5,236 +/- 325 mumol/l red blood cell/hr (p
      less than 0.01) and 166 +/- 21 to 220 +/- 24 mumol/l red blood cell/hr (p less
      than 0.05), respectively. Mean intracellular Na+ content in erythrocytes
      decreased from 11.4 +/- 0.40 to 10.0 +/- 0.33 mmol/l (p less than 0.01) and
      exchangeable Na+ from 39.8 +/- 0.6 mmol/kg to 35.6 +/- 0.6 mmol/kg (p less than
      0.001). Sodium reduction correlated with the recovery of Na(+)-K(+)-Cl-
      cotransport activity (r = -0.65, p less than 0.01). During treatment, systolic
      and diastolic blood pressures were reduced significantly (p less than 0.01). In
      12 patients treated with hydrochlorothiazide, Na(+)-K(+)-Cl- cotransport, Na(+)
      K+ pump, Na(+)-Li+ countertransport, and Na+ permeability did not change
      significantly while Na+ content decreased from 11.7 +/- 0.3 to 10.3 +/- 0.2
      mmol/l (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1999366
TI  - High NaCl diet enhances arterial baroreceptor reflex in NaCl-sensitive
      spontaneously hypertensive rats.
AB  - Previous studies from our laboratory have shown that arterial baroreceptor reflex
      control of lumbar sympathetic nerve activity is blunted in the NaCl-sensitive
      spontaneously hypertensive rat (SHR-S) compared with either the NaCl-resistant
      spontaneously hypertensive rat (SHR-R) or the normotensive Wistar-Kyoto (WKY)
      rat. In the current study, the effect of dietary NaCl supplementation on arterial
      baroreceptor reflex control of lumbar sympathetic nerve activity and heart rate
      was assessed in SHR-S and control SHR-R and WKY rats. Male SHR-S, SHR-R, and WKY
      rats were fed diets containing either 1% or 8% NaCl beginning at 7 weeks of age
      and were studied at age 9-10 weeks. Arterial baroreceptor reflex-mediated changes
      in lumbar sympathetic nerve activity and heart rate were recorded in conscious,
      unrestrained rats during phenylephrine-induced (15-40 micrograms/kg/min) and
      nitroprusside-induced (15-300 micrograms/kg/min) changes in mean arterial
      pressure. SHR-S maintained on a 1% NaCl diet had blunted baroreceptor reflex
      control of lumbar sympathetic nerve activity during acute increases in MAP
      compared with SHR-R and WKY rats (p less than 0.05). After ingestion of the 8%
      NaCl diet, this blunting was absent, indicating enhancement of baroreceptor
      reflex control of lumbar sympathetic nerve activity. SHR-S maintained on a 1%
      NaCl diet also had blunted arterial baroreceptor control of lumbar sympathetic
      nerve activity during nitroprusside-induced decreases in mean arterial pressure
      compared with WKY rats, but this was not significantly altered during ingestion
      of the 8% NaCl diet.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1999368
TI  - Transgenic animals. New approaches to hypertension research.

PMID- 1999367
TI  - Relation of electrolytes to blood pressure in men. The Yi people study.
AB  - The relations of sodium, potassium, calcium, and magnesium to blood pressure were
      investigated in four groups of men (119 high-mountain Yi farmers, 114
      mountainside Yi farmers, 89 Yi migrants, and 97 Han people) with a wide range of
      electrolyte intake in Puge County, Sichuan Province, People's Republic of China.
      Electrolytes were measured in diet, serum, and urine. Sodium excretion was 73.9
      mmol/24 hr in high-mountain Yi farmers, 117.9 mmol/24 hr in mountainside Yi
      farmers, 159.4 mmol/24 hr in Yi migrants, and 186.0 mmol/24 hr in the Han people.
      In ecological correlation analysis, dietary and urinary sodium were significantly
      and positively correlated with both systolic and diastolic pressure, whereas
      serum sodium showed no relation with blood pressure. In diet, serum, and urine,
      potassium was negatively related to systolic and diastolic pressure, whereas the
      sodium/potassium ratio showed a positive association. With regard to calcium,
      only urinary excretion was significantly and positively related to blood
      pressure. No relation was found between magnesium and blood pressure. Analyses at
      the individual level confirmed the results for sodium and potassium seen at the
      ecological level, but in addition, dietary calcium and magnesium were
      significantly and negatively correlated to both systolic and diastolic pressure,
      and urinary magnesium was inversely related to diastolic pressure. These
      relations persisted after controlling for age, body mass index (kg/m2), heart
      rate, alcohol, and total energy intake in multiple regression analysis performed
      separately for electrolytes in diet, serum, and urine. In multiple regression
      analysis, an increase in sodium intake of 100 mmol/day corresponded to an
      increase of 2.3 mm Hg systolic blood pressure and 1/8 mm Hg diastolic
      pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1999369
TI  - Systolic Hypertension in the Elderly Program (SHEP). Part 7: Baseline laboratory
      characteristics.

PMID- 1999370
TI  - Systolic Hypertension of the Elderly Program (SHEP). Part 9: Behavioral
      characteristics.

PMID- 1999371
TI  - Systolic Hypertension in the Elderly Program (SHEP). Part 2: Screening and
      recruitment.

PMID- 1999372
TI  - Systolic Hypertension of the Elderly Program (SHEP). Part 10: Analysis.
AB  - The SHEP is a randomized, placebo-controlled trial that will follow standard
      clinical trial principles in analyzing data relating to its proposed hypotheses.
      The protocol has stated a priori the main objective as well as the secondary
      subgroup hypotheses. Sample size calculations for SHEP have accounted for dropins
      to and drop-outs from active therapy as well as for the risk of nonstroke death.
      The sample size achieved (4,736 participants) should be adequate to address the
      proposed questions. Monitoring procedures have been described and established. A
      data and safety monitoring board that uses these procedures is closely following
      the data from the trial. The board will periodically examine the data to
      determine whether termination of the study is warranted.

PMID- 1999373
TI  - Systolic Hypertension in the Elderly Program (SHEP). Part 1: Rationale and
      design.

PMID- 1999374
TI  - Systolic Hypertension in the Elderly Program (SHEP). Part 3: Sociodemographic
      characteristics.

PMID- 1999375
TI  - Systolic Hypertension in the Elderly Program (SHEP). Part 4: Baseline medical
      history findings.

PMID- 1999376
TI  - Systolic Hypertension in the Elderly Program (SHEP). Part 5: Baseline blood
      pressure and pulse rate measurements.

PMID- 1999377
TI  - Systolic Hypertension in the Elderly Program (SHEP). Part 6: Baseline physical
      examination findings.

PMID- 1999378
TI  - Patient trapped in mammography unit compression system.

PMID- 1999379
TI  - Potassium sensitivity errors on the radiometer ABL4 blood gas analyzer.

PMID- 1999380
TI  - Physical locations of bglA and serA on the Escherichia coli K-12 chromosome.

PMID- 1999381
TI  - Localization of the Escherichia coli amtA gene to 95.8 minutes.

PMID- 1999382
TI  - Locations of genes in the nar-adhE region of the Escherichia coli K-12
      chromosome.

PMID- 1999383
TI  - Freeze-substitution of gram-negative eubacteria: general cell morphology and
      envelope profiles.
AB  - Freeze-substitution was performed on strains of Escherichia coli, Pasteurella
      multocida, Campylobacter fetus, Vibrio cholerae, Pseudomonas aeruginosa,
      Pseudomonas putida, Aeromonas salmonicida, Proteus mirabilis, Haemophilus
      pleuropneumoniae, Caulobacter crescentus, and Leptothrix discophora with a
      substitution medium composed of 2% osmium tetroxide and 2% uranyl acetate in
      anhydrous acetone. A thick periplasmic gel ranging from 10.6 to 14.3 nm in width
      was displayed in E. coli K-12, K30, and His 1 (a K-12 derivative containing the
      K30 capsule genes), P. multocida, C. fetus, P. putida, A. salmonicida, H.
      pleuropneumoniae, and P. mirabilis. The other bacteria possessed translucent
      periplasms in which a thinner peptidoglycan layer was seen. Capsular
      polysaccharide, evident as electron-dense fibers radiating outward perpendicular
      to the cell surface, was observed on E. coli K30 and His 1 and P. mirabilis
      cells. A more random arrangement of fibers forming a netlike structure was
      apparent surrounding cells of H. pleuropneumoniae. For the first time a capsule,
      distinct from the sheath, was observed on L. discophora. In all instances,
      capsular polysaccharide was visualized in the absence of stabilizing agents such
      as homologous antisera or ruthenium red. Other distinct envelope structures were
      observed external to the outer membrane including the sheath of L. discophora and
      the S layers of A. salmonicida A450 and C. crescentus CB15A. We believe that the
      freeze-substitution technique presents a more accurate image of the structural
      organization of these cells and that it has revealed complex ultrastructural
      relationships between cell envelope constituents previously difficult to
      visualize by more conventional means of preparation.

PMID- 1999385
TI  - Genetic and biochemical characterization of a Pseudomonas solanacearum gene
      cluster required for extracellular polysaccharide production and for virulence.
AB  - Infection of host plants by Pseudomonas solanacerum results in wilting, which is
      thought to be due largely to the occlusion of xylem vessels by the P.
      solanacearum extracellular polysaccharide (EPS) that primarily consists of N
      acetylgalactosamine (GalNAc). By means of Tn3 mutagenesis, we identified a 6.5-kb
      gene cluster that contains five complementation units required for EPS production
      and virulence in this bacterium. There was positive correlation between the
      amount of EPS produced in culture and (i) in planta growth and (ii) virulence.
      Based on analysis of beta-glucuronidase-gene fusions, these genes are expressed
      both in broth cultures and in planta and may be constitutive. Both wild-type and
      mutant strains contained similar amounts of UDP-GalNAc, the predicted primary
      substrate for EPS synthesis. Thus, the EPS mutants we obtained should be useful
      in the analysis of steps in the assembly of the polysaccharide and how this
      process is related to virulence.

PMID- 1999384
TI  - Transcription attenuation-mediated control of leu operon expression: influence of
      the number of Leu control codons.
AB  - Four adjacent Leu codons within the leu leader RNA are critically important in
      transcription attenuation-mediated control of leu operon expression in Salmonella
      typhimurium and Escherichia coli (P. W. Carter, D. L. Weiss, H. L. Weith, and J.
      M. Calvo, J. Bacteriol. 162:943-949, 1985). The leader region from S. typhimurium
      was altered by site-directed mutagenesis to produce constructs having between one
      and seven adjacent Leu codons, all CUA. leu operon expression was measured in
      strains containing six of these constructs, each integrated into the chromosome
      in a single copy. Operon expression was sufficiently high that all strains grew
      in minimal medium unsupplemented by leucine. Expression of the operon was
      measured in strains cultured in such a way that their growth was limited by the
      intracellular concentration of either leucine or of leucyl-tRNA. In general, the
      leu operon for each construct responded similarly to the parent construct in
      terms of the degree of expression as a function of the degree of limitation.
      However, a strain containing (CUA)1 and, to a certain extent, a strain having
      (CUA)2 responded somewhat more sluggishly and strains containing (CUA)6 and
      (CUA)7 responded more sensitively to limitations than did the parent construct.
      In addition, DNA fragments containing the leu promoter and leader region were
      used as templates in in vitro transcription reactions employing purified RNA
      polymerase. With nucleoside triphosphate concentrations of 200 microM, RNA
      polymerase paused during transcription of the leu leader region at a site about
      95 bp downstream from the site of transcription initiation. The halftimes of the
      pause were 1 min at 37 degrees C and 3 min at 22 degrees C. The pause was
      lengthened substantially when the GTP concentration was lowered to 20 micromoles.
      Our results are interpreted most easily in terms of an all-or-none model. Given
      two Leu control codons, the operon responds with nearly maximum output over a
      wide range of leucine limitation, and that outcome does not change much with
      increasing numbers of control codons.

PMID- 1999386
TI  - Isolation and molecular characterization of the ribosomal protein L6 homolog from
      Chlamydia trachomatis.
AB  - The cloning of a Chlamydia trachomatis eukaryotic cell-binding protein reported
      earlier from our laboratory (R. Kaul, K. L. Roy, and W. M. Wenman, J. Bacteriol.
      169:5152-5156, 1987) represents an artifact generated by nonspecific
      recombination of chromosomal DNA fragments. However, the amino terminus of this
      plasmid-encoded fusion product demonstrated significant homology to Escherichia
      coli ribosomal protein L6. By using a 458-bp PstI-HindIII fragment of recombinant
      pCT161/18 (representing the 5' end of the cloned gene), we isolated and
      characterized a C. trachomatis homolog of the ribosomal protein L6 gene of E.
      coli. Sequence analysis of an 1,194-bp EcoRI-SacI fragment that encodes
      chlamydial L6 (designated CtaL6e) revealed a 552-bp open reading frame comprising
      183 amino acids and encodes a protein with a molecular weight of 19,839.
      Interestingly, complete gene homology between C. trachomatis serovars L2 and J,
      each of which exists as a single copy per genome, was observed. Expression of a
      plasmid-encoded gene product is dependent on the lac promoter, since no product
      was obtained if the open reading frame was oriented in opposition to the lac
      promoter. Immunoblotting of purified ribosomes revealed functional, as well as
      antigenic, homology between the E. coli and C. trachomatis ribosomal L6 proteins.

PMID- 1999387
TI  - Secretion of hybrid proteins by the Yersinia Yop export system.
AB  - After incubation at 37 degrees C in the absence of Ca2+ ions, pathogenic strains
      of Yersinia spp. release large amounts of a set of plasmid-encoded proteins
      called Yops. The secretion of these proteins, involved in pathogenicity, occurs
      via a mechanism that involves neither the removal of a signal sequence nor the
      recognition of a C-terminal domain. Analysis of deletion mutants allowed the
      secretion recognition domain to be localized within the 48 N-terminal amino acids
      of protein YopH, within the 98 N-terminal residues of protein YopE, and within
      the 76 N-terminal residues of YopQ. Comparison of these regions failed to reveal
      any sequence similarity, suggesting that the secretion signal of Yop proteins is
      conformational rather than sequential. Hybrid proteins containing the amino
      terminal part of YopH fused to either the alpha-peptide of beta-galactosidase or
      to alkaline phosphatase deprived of its signal sequence were efficiently secreted
      to the Yersinia culture medium. This observation opens new prospects in using
      Yersinia spp. as chimeric-protein producers and as potential live carriers for
      foreign antigens.

PMID- 1999388
TI  - Primary structure of xylene monooxygenase: similarities to and differences from
      the alkane hydroxylation system.
AB  - Xylene monooxygenase, encoded by the TOL plasmid of Pseudomonas putida, catalyzes
      the oxidation of toluene and xylenes and consists of two different subunits
      encoded by xylA and xylM. In this study, the complete nucleotide sequences of
      these genes were determined and the amino acid sequences of the xylA and xylM
      products were deduced. The XylM sequence had a 25% homology with alkane
      hydroxylase, which catalyzes the omega-hydroxylation of fatty acids and the
      terminal hydroxylation of alkanes. The sequence of the first 90 amino acids of
      XylA exhibited a strong similarity to the sequence of chloroplast-type
      ferredoxins, whereas the rest of the XylA sequence resembled that of ferredoxin
      NADP+ reductases. Based on this information, the structure and function of xylene
      monooxygenase were deduced. XylM may be a catalytic component for the
      hydroxylation of the carbon side chain of toluene and xylenes and, as is the
      alkane hydroxylase protein, may be a membrane-bound protein containing ferrous
      ion as a prosthetic group. XylA may have two domains consisting of an N-terminal
      region similar to chloroplast-type ferredoxins and a C-terminal region similar to
      ferredoxin-NADP+ reductases. The ferredoxin portion of XylA may contain a [2Fe
      2S] cluster and reduce the oxidized form of the XylM hydroxylase. The activity
      determined by the C-terminal region of the XylA sequence may be the reduction of
      the oxidized form of ferredoxin by concomitant oxidation of NADH.

PMID- 1999389
TI  - Structure of Escherichia coli K-12 miaA and characterization of the mutator
      phenotype caused by miaA insertion mutations.
AB  - Previously, we reported several unusual relationships between the 2-methylthio-N6
      (delta 2-isopentenyl)adenosine-37 (ms2i6A-37) tRNA modification and spontaneous
      mutagenesis in Escherichia coli K-12 (D. M. Connolly and M. E. Winkler, J.
      Bacteriol. 171:3233-3246, 1989). To confirm and extend these observations, we
      determined the structure of miaA, which mediates the first step of ms2i6A-37
      synthesis, and characterized the miaA mutator phenotype. The most likely
      translation start of miaA overlaps the last two codons of mutL, which encodes a
      protein required for methyl-directed mismatch repair. This structural arrangement
      confirms that miaA and mutL are in the same complex operon. The miaA gene
      product, delta 2-isopentenylpyrophosphate transferase, shows extensive homology
      with the yeast MOD5 gene product, and both enzymes contain a substrate binding
      site found in farnysyl pyrophosphate synthetase and a conserved putative ATP/GTP
      binding site. Insertions in miaA cause exclusively GC----TA transversions, which
      contrasts with the GC----AT and AT----GC transitions observed in mutL mutants. To
      correlate the absence of the ms2i6A-37 tRNA modification directly with the
      mutator phenotype, we isolated a unique suppressor of a leaky miaA(ochre)
      mutation. The miaD suppressor mapped to 99.75 min, restored the ms2i6A-37 tRNA
      modification to miaA(ochre) mutants, and abolished the miaA mutator phenotype. We
      speculate that miaD causes a decrease in ms2i6A-37 tRNA demodification or an
      increase in miaA gene expression but not at the level of operon transcription.
      Together, these observations support the idea that the ms2i6A-37 tRNA
      modification acts as a physiological switch that modulates spontaneous mutation
      frequency and other metabolic functions.

PMID- 1999390
TI  - Isolation, cloning, mapping, and nucleotide sequencing of the gene encoding
      flavodoxin in Escherichia coli.
AB  - The flavodoxins constitute a highly conserved family of small, acidic electron
      transfer proteins with flavin mononucleotide prosthetic groups. They are found in
      prokaryotes and in red and green algae, where they provide electrons at low
      potentials for the reduction of nitrogen by nitrogenase, for the light-dependent
      reduction of NADP+ in photosynthesis, and for the reduction of sulfite. Proteins
      with the physical characteristics of flavodoxins have been implicated in the
      reductive activation of pyruvate formate-lyase and cobalamin-dependent methionine
      synthase in Escherichia coli. We have purified flavodoxin to homogeneity from E.
      coli, determined its N-terminal amino acid sequence, and used this sequence to
      construct a 64-fold degenerate oligonucleotide probe for the flavodoxin gene.
      Because the phenotype of a flavodoxin mutant is not known, we used this
      degenerate probe to screen the phages of the Kohara library and identified two
      phages, with inserts mapping at approximately 16 min, that hybridized to the
      probe. The flavodoxin gene, designated fldA, was subcloned from the DNA in the
      overlap region of these two clones. The deduced amino acid sequence, determined
      by nucleotide sequencing of the flavodoxin gene, shows strong homology with
      flavodoxins from nitrogen-fixing bacteria and cyanobacteria. The fldA gene maps
      at 15.9 min on the E. coli chromosome and is transcribed in a counterclockwise
      direction.

PMID- 1999391
TI  - RcsA, an unstable positive regulator of capsular polysaccharide synthesis.
AB  - RcsA is an unstable positive regulator required for the synthesis of colanic acid
      capsular polysaccharide in Escherichia coli. Degradation of the RcsA protein in
      vivo depends on the ATP-dependent Lon protease. DNA sequence analysis of the rcsA
      gene reveals a single open reading frame for a 23,500-Da highly basic protein (pI
      = 9.9), consistent with the observed size of the purified subunit of RcsA. The
      DNA and protein sequences are highly homologous to the rcsA gene and protein from
      Klebsiella pneumoniae and other species. The carboxy-terminal region of RcsA
      contains a possible helix-turn-helix DNA-binding motif that resembles sequences
      found at the carboxy terminus of RcsB, another positive regulator of capsule
      synthesis, and in several other transcriptional regulators including members of
      the LuxR family. rcsA62, a mutation in rcsA that leads to increased capsule
      synthesis, encodes a protein designated RcsA*, which differs from wild-type RcsA
      only in the replacement of Met-145 by valine. The RcsA* protein is subject to Lon
      dependent degradation. The stability of wild-type RcsA in vivo is increased by
      multicopy RcsB. Conversely, RcsA is degraded more rapidly in rcsB mutant hosts
      than in wild-type hosts. These results suggest that RcsA and RcsB interact in
      vivo and are consistent with genetic experiments that indicate an interaction
      between RcsA and RcsB. Based on these experiments, we propose a model for capsule
      regulation in which RcsA interacts directly with RcsB to promote transcription of
      the genes for capsule synthesis.

PMID- 1999393
TI  - MAL11 and MAL61 encode the inducible high-affinity maltose transporter of
      Saccharomyces cerevisiae.
AB  - We have investigated the transport of maltose in a genetically defined maltose
      fermenting strain of Saccharomyces cerevisiae carrying the MAL1 locus. Two
      kinetically different systems were identified: a high-affinity transporter with a
      Km of 4 mM and a low-affinity transporter with a Km of 70 to 80 mM. The high
      affinity maltose transporter is maltose inducible and is encoded by the MAL11
      (and/or MAL61) gene of the MAL1 (and/or MAL6) locus. The low-affinity maltose
      transporter is expressed constitutively and is not related to MAL11 and/or MAL61.
      Both maltose transporters are subject to glucose-induced inactivation.

PMID- 1999392
TI  - The trmA promoter has regulatory features and sequence elements in common with
      the rRNA P1 promoter family of Escherichia coli.
AB  - The tRNA(m5U54)methyltransferase, whose structural gene is designated trmA,
      catalyzes the formation of 5-methyluridine in position 54 of all tRNA species in
      Escherichia coli. The synthesis of this enzyme has previously been shown to be
      both growth rate dependent and stringently regulated, suggesting regulatory
      features similar to those of rRNA. We have determined the complete nucleotide
      sequence of the trmA operon in E. coli and the sequence of the trmA promoter
      region in Salmonella typhimurium and also analyzed the transcriptional regulation
      of the gene. The trmA and the btuB (encoding the vitamin B12 outer membrane
      receptor protein) promoters are divergent promoters separated by 102 bp between
      the transcriptional start sites. The trmA promoters of both E. coli and S.
      typhimurium share promoter elements with the rRNA P1 promoter. The sequence
      downstream from the -10 region of the trmA promoter is homologous to the
      discriminatory region found in stringently regulated promoters. Next to and
      upstream from the -10 region is a sequence, TCCC, in the trmA promoter that is
      present in all of the seven rRNA P1 promoters and in some tRNA promoters but not
      in any other sigma 70 promoter. However, a similar motif is also found in
      promoters transcribed by the heat shock sigma factor sigma 32. The trmA gene is
      transcribed as a monocistronic operon, and the 3' end of the transcript is shown
      to be located downstream from a dyad symmetry region not followed by a poly(U)
      stretch. Using a trmA-cat operon fusion, we show that the growth rate-dependent
      regulation of trmA resembles that of rRNA and operates at the level of
      transcription.

PMID- 1999394
TI  - Role of host factors in the regulation of the enterotoxin B gene.
AB  - The levels of staphylococcal enterotoxin B (SEB) produced by various naturally
      occurring toxinogenic strains of Staphylococcus aureus are highly variable. The
      SEB gene (seb) from a high-producer strain, S6, has previously been cloned and
      characterized. Cloning and nucleotide sequence analysis of the upstream region of
      the seb gene from DU4916 and COL (medium- and low-level toxin-producer strains,
      respectively) showed that their sequence was identical to that of the seb gene
      from strain S6. Strains carrying the cloned seb gene from DU4916 and COL produced
      similar levels of SEB protein and mRNA to those produced by strains carrying the
      cloned seb gene from strain S6. An RNA encoded by the delta-lysin gene (hld) has
      been shown to regulate the genes for a number of extracellular proteins,
      including SEB. Northern (RNA) blot analysis showed that variable levels of hld
      RNA were present in various SEB-producer strains, with the order being S6 greater
      than DU4916 greater than COL. Our results suggest that differences in host
      factor(s), including the hld RNA, are responsible for the production of different
      amounts of SEB by many naturally occurring strains.

PMID- 1999395
TI  - Molecular cloning of an alcohol (butanol) dehydrogenase gene cluster from
      Clostridium acetobutylicum ATCC 824.
AB  - In Clostridium acetobutylicum, conversion of butyraldehyde to butanol is
      enzymatically achieved by butanol dehydrogenase (BDH). A C. acetobutylicum gene
      that encodes this protein was identified by using an oligonucleotide designed on
      the basis of the N-terminal amino acid sequence of purified C. acetobutylicum
      NADH-dependent BDH. Enzyme assays of cell extracts of Escherichia coli harboring
      the clostridial gene demonstrated 15-fold-higher NADH-dependent BDH activity than
      untransformed E. coli, as well as an additional NADPH-dependent BDH activity.
      Kinetic, sequence, and isoelectric focusing analyses suggest that the cloned
      clostridial DNA contains two or more distinct C. acetobutylicum enzymes with BDH
      activity.

PMID- 1999397
TI  - The cholinesterases.

PMID- 1999396
TI  - Genes for 7S RNAs can replace the gene for 4.5S RNA in growth of Escherichia
      coli.
AB  - 4.5S RNAs of eubacteria and 7S RNAs of archaebacteria and eukaryotes exist in a
      hairpin conformation. The apex of this hairpin displays structural and sequence
      similarities among both 4.5S and 7S RNAs. Furthermore, a hyphenated sequence of
      16 nucleotides is conserved in all eubacterial 4.5S RNAs examined. In this
      article I report that 7S RNAs that contain this 16-nucleotide sequence are able
      to replace 4.5S RNAs and permit growth of Escherichia coli.

PMID- 1999398
TI  - Thymosin beta 4 and Fx, an actin-sequestering peptide, are indistinguishable.
AB  - At least 50% of the actin in resting human platelets is unpolymerized, and the
      bulk of this unpolymerized actin is complexed with a recently identified acidic,
      heat-stable 5-kDa peptide, named "Fx." Purified Fx binds stoichiometrically to
      muscle G-actin, forming a complex identifiable by nondenaturing polyacrylamide
      gel electrophoresis. Formation of the complex inhibits salt-induced
      polymerization of G-actin. Here we report that Fx is indistinguishable from
      thymosin beta 4, an acidic, heat-stable 5-kDa peptide first isolated from calf
      thymus and thought to be a thymic hormone. The complete amino acid sequence of Fx
      was determined and was found to be identical with that of thymosin beta 4.
      Authentic thymosin beta 4 is functionally equivalent to Fx, forming a 1:1 complex
      with actin monomers and inhibiting polymerization. The widespread distribution
      and high intracellular concentration of thymosin beta 4 (Fx) strongly suggest
      that it plays a significant role in regulating actin polymerization in many cell
      types.

PMID- 1999399
TI  - Site-specific mutagenesis of an essential histidine residue in pancreatic
      cholesterol esterase.
AB  - The histidine residue essential for the catalytic activity of pancreatic
      cholesterol esterase (carboxylester lipase) has been identified in this study
      using sequence comparison and site-specific mutagenesis techniques. In the first
      approach, comparison of the primary structure of rat pancreatic cholesterol
      esterase with that of acetylcholinesterase and cholinesterase revealed two
      conserved histidine residues located at positions 420 and 435. The sequence in
      the region around histidine 420 is quite different between the three enzymes.
      However, histidine 435 is located in a 22-amino acid domain that is 47%
      homologous with other serine esterases. Based on this sequence homology, it was
      hypothesized that histidine 435 is the histidine residue essential for catalytic
      activity of cholesterol esterase. The role of His435 in the catalytic activity of
      pancreatic cholesterol esterase was then studied by the site-specific mutagenesis
      technique. Substitution of the histidine in position 435 with glutamine,
      arginine, alanine, serine, or aspartic acid abolished the ability of cholesterol
      esterase to hydrolyze p-nitrophenyl butyrate and cholesterol [14C]oleate. In
      contrast, mutagenesis of the histidine residue at position 420 to glutamine had
      no effect on cholesterol esterase enzyme activity. The results of this study
      strongly suggested that histidine 435 may be a component of the catalytic triad
      of pancreatic cholesterol esterase.

PMID- 1999400
TI  - Insulin and nonhydrolyzable GTP analogs induce translocation of GLUT 4 to the
      plasma membrane in alpha-toxin-permeabilized rat adipose cells.
AB  - Rat adipose cells treated with Staphylococcus aureus alpha-toxin are permeable
      and retain their ability to respond to insulin after hormone treatment. The GLUT
      4 glucose transporter isoform, specific to fat and muscle cells, is translocated
      normally from low density microsomes to the plasma membrane in permeabilized
      cells. Addition of guanosine 5'-O-(3-thiotriphosphate), guanylyl
      imidodiphosphate, or guanylyl beta, gamma-methylenediphosphate to permeabilized
      adipocytes induces an insulin-like translocation of GLUT 4 to the plasma
      membrane; GTP or adenosine 5'-(beta, gamma-imino)triphosphate has no effect. No
      translocation of GLUT 4 is observed when GTP analogs are added to intact
      adipocytes. These results suggest the involvement of a GTP-binding protein in
      insulin-triggered recruitment of GLUT 4 to the cell surface.

PMID- 1999401
TI  - Substitution of the conserved tryptophan 31 in Escherichia coli thioredoxin by
      site-directed mutagenesis and structure-function analysis.
AB  - All prokaryotic and eukaryotic thioredoxins contain a conserved tryptophan
      residue, exposed at the active site disulfide/dithiol. The role of this W31 in
      Escherichia coli thioredoxin (Trx) was studied by site-directed mutagenesis. Four
      mutant Trx with W31Y, W31F, W31H, and W31A replacements were characterized. Very
      low tryptophan fluorescence emission from the remaining W28 was observed in all
      mutant Trx; reduction resulted in large, but variable increases (up to 11-fold)
      of fluorescence, to levels higher than in native or denatured wild-type Trx,
      demonstrating a previously postulated change involving W28. All W31 mutant Trx
      were good substrates for E. coli thioredoxin reductase. Compared with wild type,
      the apparent Km values were increased less than 2-fold for the W31A, W31H, and
      W31F Trx and the W31Y Trx showed even slightly higher catalytic efficiency
      (kcat/Km value). Functions of reduced Trx with ribonucleotide reductase and in
      reduction of insulin disulfides were more strongly influenced by the W31
      replacements, in particular at low pH for A and H residues. T7 DNA polymerase
      activity generated by T7 gene 5 protein and reduced Trx was lowered by large
      factors for W31Y, W31A, or W31H compared with W31F or the wild-type protein. The
      in vivo function of Trx was studied by using pUC118-trxA expression in an E. coli
      trxA- background. The trxA genes with W31Y and W31F substitutions restored, fully
      and partly, the methionine sulfoxide utilization of a trxA- metE- test strain;
      W31A and W31H mutations resulted in no growth. Propagation of M13 was moderately
      impeded by W31Y and W31F or severely by W31A and W31H replacements. Growth of a
      phage T3/7 hybrid was possible only with the W31Y and W31F substitutions
      reflecting the in vitro results for T7 DNA polymerase.

PMID- 1999403
TI  - Carbohydrate variant of the recombinant beta-subunit of human choriogonadotropin
      expressed in baculovirus expression system.
AB  - The beta-subunit of human choriogonadotropin (hCG) has two complex type N-linked
      and four O-linked carbohydrate chains. To further evaluate the specificity of the
      carbohydrate moiety on the hCG function, we have expressed hCG beta subunit in
      the baculovirus insect cell system to modify its carbohydrate structures. The
      recombinant hCG beta (rhCG beta) was efficiently secreted in the medium and was
      purified to homogeneity by immunoaffinity chromatography using a highly specific
      monoclonal antibody against hCG beta. The homogeneity of the recombinant subunit
      was established by sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      performed under reducing and nonreducing conditions and reverse phase high
      performance liquid chromatography. rhCG beta had molecular weights of 22,500 and
      33,000 under reducing and nonreducing conditions, respectively. Digestion with N
      glycanase cleaved the Mr = 22,500 protein to 18,000, while digestion with Endo H
      or Endo F yielded an additional protein band of 20,500 on sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. The carbohydrate analysis by pulse
      amperometry yielded the relative number of 2.5, 2.4, 3.7, and 11.3 residues of
      fucose, N-acetylgalactosamine, galactose, and mannose, respectively, based on a
      value of 4 residues for N-acetylglucosamine. Lectin binding studies showed rhCG
      beta to bind with concanavalin A with a high affinity and not with wheat germ
      agglutinin. In the studies with endoglycosidases together with the carbohydrate
      analysis and lectin binding properties, rhCG beta appears to have two high
      mannose-type N-linked and three to four O-linked carbohydrate simple disaccharide
      chains. The carbohydrate modification of the beta-subunit did not alter its
      immunopotency and its ability to combine with hCG alpha. The reconstituted
      hormone made up of rhCG beta and hCG alpha was found to be similar to hCG in
      biological properties such as receptor binding and in its ability to stimulate
      cAMP and steroidogenesis.

PMID- 1999402
TI  - Demonstration of apolipoprotein CII in guinea pigs. Functional characteristics,
      cDNA sequence, and tissue expression.
AB  - In contrast to plasma from other mammals, guinea pig plasma does not stimulate
      the activity of lipoprotein lipases in vitro. This had led previously to the
      conclusion that guinea pigs lack an analogue to apolipoprotein CII (apoCII). By
      adsorption of lipid-binding proteins to lipid droplets, thereby separating them
      from other plasma components, we could demonstrate apoCII-like activity in guinea
      pig plasma. On electrophoresis, the CII-like activity co-migrated with one
      isoform of guinea pig apolipoprotein CIII, identified by amino-terminal amino
      acid sequence determination (40 residues). By isoelectric focusing in a narrow pH
      gradient, the activating protein was separated sufficiently from the dominating
      apoCIII isoform to allow sequence determination of 8 residues from the amino
      terminus. Six of these were identical to corresponding residues in apoCII from
      dog and monkey. With the aid of a human apoCII cDNA probe we identified one cross
      hybridizing mRNA species (approximately 600 nucleotides) on Northern blots of
      guinea pig liver. Three positive clones were isolated from a guinea pig liver
      cDNA library using the same cDNA probe. The nucleotide sequence showed extensive
      similarities to the previously known human, monkey, and canine sequences, but the
      signal peptide was 3 amino acid residues longer in the guinea pig protein, and
      there was a deletion of 4 residues in the putative lipid binding domain. Northern
      blot analyses indicated that guinea pig apoCII is mainly expressed in the liver
      with little or no contribution from the intestine.

PMID- 1999404
TI  - Characterization of a limited trypsin digestion form of eukaryotic elongation
      factor 1 alpha.
AB  - The involvement of the first 69 amino acids of eukaryotic elongation factor 1
      alpha (EF-1 alpha) from rabbit reticulocyte in GTP and aminoacyl-tRNA binding has
      been analyzed by a variety of techniques. EF-1 alpha was subjected to limited
      trypsin digestion, which cleaved predominantly at residues 36 and 69. A digested
      form of Escherichia coli EF-Tu, similar to the one used for this study, has been
      characterized by x-ray crystallography and is used as a structural model for EF-1
      alpha. This form of EF-1 alpha bound E. coli Phe-tRNAPhe similar to the wild type
      protein, but lacked activity in phenylalanine polymerization with poly(U)
      programmed ribosomes. These results were obtained regardless of whether or not
      loosely associated N-terminal peptides were removed by gel filtration
      chromatography. The digested EF-1 alpha also shows reduced GTPase activity, but
      the activity is stimulated by both ribosomes and aminoacyl-tRNA. Binding of EF-1
      alpha to the 80 S ribosome, as determined by association of reductively
      methylated protein through Sepharose 6B chromatography, is reduced approximately
      7-fold for the limited digested form of the protein. Limited digested EF-1 alpha
      can, however, be photo-cross-linked with GTP and 3'-p-azido-GTP similar to intact
      EF-1 alpha. Chemical cross-linking with oxidized GTP, fluorosulfonylbenzoyl-GTP,
      or with trans-diaminedichloroplatinum(II) and GPT, shows a similar modification
      of both intact and limited digested EF-1 alpha. In order to further localize the
      modification site with the GTP reagents and assure that modification was not
      occurring in the first 69 amino acids, intact EF-1 alpha was modified with these
      same reagents. Limited trypsin digestion of modified protein indicates that none
      of these reagents cross-links GTP to the first 69 amino acids of EF-1 alpha,
      which includes the first GTP binding consensus element, GXXXXGK.

PMID- 1999405
TI  - Purification and characterization of an oxygen-insensitive NAD(P)H nitroreductase
      from Enterobacter cloacae.
AB  - The reductive products of several nitroaromatic compounds have been found to be
      toxic, mutagenic, and carcinogenic. The nitroreductases present in intestinal
      microflora have been implicated in the biotransformation of these compounds to
      their deleterious metabolites. A "classical" nitroreductase has been purified
      from Enterobacter cloacae 587-fold using a protocol which yields approximately 1
      mg of purified nitroreductase from 10 liters of cell culture. An analysis of the
      physical properties of the nitroreductase indicates that the enzyme is active as
      a monomer with a calculated molecular mass of 27 kDa. FMN has been identified as
      a required flavin cofactor and is present at a stoichiometry of 0.88 mol of FMN
      bound/mol of active enzyme. The enzyme was found capable of reducing
      nitrofurazone under aerobic conditions indicating that the mechanism involves an
      obligatory two-electron transfer. Thus, this enzyme can be classified as an
      oxygen-insensitive nitroreductase. The purified nitroreductase can utilize either
      NADH or NADPH as a source of reducing equivalents and can reduce a variety of
      nitroaromatic compounds including nitrofurans and nitrobenzenes as well as
      quinones. Studies in which the rates of nitroreduction for a series of para
      substituted nitrobenzene derivatives were determined suggest that a linear free
      energy relationship exists between the rate and the redox midpoint potential of
      the substrate.

PMID- 1999406
TI  - Cloning, nucleotide sequence, and expression of the nitroreductase gene from
      Enterobacter cloacae.
AB  - The "classical" nitroreductases of enteric bacteria are flavoproteins which
      catalyze the reduction of a variety of nitroaromatic compounds to metabolites
      which are highly toxic, mutagenic, or carcinogenic. The gene for the
      nitroreductase Enterobacter cloacae has now been cloned using an antibody
      specific to this protein. The nucleotide sequence of the structural gene and
      flanking regions are reported. Sequence analysis indicates that this gene belongs
      to a gene family of flavoproteins which have not been previously described.
      Analysis of the 5'-untranslated region reveals the presence of putative
      regulatory elements which may be involved in the modulation of the expression of
      this enzyme. The cloned gene was placed under the control of a T7 promoter for
      overexpression of the protein in Escherichia coli. The expressed recombinant
      protein was purified to homogeneity and exhibited physical, spectral, and
      catalytic properties identical to the protein isolated from E. cloacae.

PMID- 1999407
TI  - An analysis of lactose permease "sugar specificity" mutations which also affect
      the coupling between proton and lactose transport. I. Val177 and Val177/Asn319
      permeases facilitate proton uniport and sugar uniport.
AB  - The sugar specificity mutants of the lactose permease containing Val177 or
      Val177/Asn319 were analyzed with regard to their ability to couple H+ and sugar
      co-transport. Both mutants were able to transport lactose downhill to a
      significant degree. The Val177 mutant was partially defective in the active
      accumulation of galactosides, whereas the Val177/Asn319 mutant was completely
      defective in the uphill accumulation of sugars. With regard to coupling, the
      Val177 mutant was shown to catalyze the uncoupled transport of H+ to a
      substantial degree. This led to a decrease in the H+ electrochemical gradient
      under aerobic conditions and also resulted in faster H+ uptake when a transient
      H+ electrochemical gradient was generated under anaerobic conditions.
      Interestingly, galactosides were shown to diminish the rate of uncoupled H+
      transport in the Val177 strain. The Val177/Asn319 strain also catalyzed uncoupled
      H+ transport, but to a lesser degree than the single Val177 mutant. In addition,
      the Val177/Asn319 mutant was shown to transport galactosides with or without H+.
      The observed H+/lactose stoichiometry was 0.30 in the double mutant compared to
      0.98 in the wild-type strain. When an H+ electrochemical gradient was generated
      across the membrane, the Val177/Asn319 mutant permease was shown to facilitate an
      extremely rapid net H+ leak if nonmetabolizable galactosides had been
      equilibrated across the membrane. The mechanism of this leak is consistent with a
      circular pathway involving H+/galactoside influx and uncoupled galactoside
      efflux. The magnitude of the H+ leak in the presence of nonmetabolizable
      galactosides was so great in the double mutant that low concentrations of certain
      galactosides (i.e. 0.5 mM thiodigalactoside) resulted in a complete inhibition of
      growth. These results are discussed with regard to the possibility that cation
      and sugar binding to the lactose permease may involve a direct physical coupling
      at a common recognition site.

PMID- 1999408
TI  - An analysis of lactose permease "sugar specificity" mutations which also affect
      the coupling between proton and lactose transport. II. Second site revertants of
      the thiodigalactoside-dependent proton leak by the Val177/Asn319 permease.
AB  - The double mutant of the lactose permease containing Val177/Asn319 exhibits
      proton leakiness by two pathways (see Brooker, R. J. (1991) J. Biol Chem. 266,
      4131-4138). One type of H+ leakiness involves the uncoupled influx of H+ (leak A
      pathway) while a second type involves the coupled influx of H+ and galactosides
      in conjunction with uncoupled galactoside efflux (leak B pathway). In the current
      study, 14 independent lactose permease mutants were isolated from the
      Val177/Asn319 parent which were resistant to thiodigalactoside growth inhibition
      but retained the ability to transport maltose. All of these mutants contained a
      third mutation (besides Val177/Asn319) at one of two sites. Eight of the mutants
      had Ile303 changed to Phe, while six of the mutants had Tyr236 changed to Asn or
      His. Each type of triple mutant was characterized with regard to sugar transport,
      H+ leakiness, and sugar specificity. Like the parental strain, all three types of
      triple mutant showed moderate rates of downhill lactose transport and were
      defective in the uphill accumulation of sugars. However, with regard to proton
      leakiness, the triple mutants fell into two distinct categories. The mutant
      containing Phe303 was generally less H+ leaky than the parent either via the leak
      A or leak B pathway. In contrast, the triple mutants containing position 236
      substitutions (Asn or His) were actually more H+ leaky via the leak A pathway and
      exhibited similar H+ leakiness via the leak B pathway at high thiodigalactoside
      concentrations. The ability of the position 236 mutants to grow better than the
      parent in the presence of low concentrations of thiodigalactoside appears to be
      due to a decrease in affinity for this particular sugar rather than a generalized
      defect in H+ leakiness. Finally, the triple mutants showed a sugar specificity
      profile which was different from either the Val177/Asn319 parent, the single
      Val177 mutant, or the wild-type strain. These results are discussed with regard
      to the effects of mutations on both the sugar and H+ transport pathways.

PMID- 1999409
TI  - DNA sequence abnormalities of human glucose-6-phosphate dehydrogenase variants.
AB  - Over 400 supposedly biochemically and genetically distinct variants of glucose-6
      phosphate dehydrogenase (G6PD) have been described in the past. In order to
      investigate these variants at the DNA sequence level we have now determined the
      relevant sequences of introns of G6PD and describe a method which allows us to
      rapidly determine the sequence of the entire coding region of G6PD. This
      technique was applied to six variants that cause G6PD deficiency to be
      functionally so severe as to result in nonspherocytic hemolytic anemia. Although
      the patients were all unrelated, G6PD Marion, Gastonia, and Minnesota each had
      identical mutations, a G----T at nucleotide (nt) 637 in exon 6 leading to a Val--
      -Leu substitution at amino acid 213. The mutations of Nashville and Anaheim were
      identical to each other, viz. G----A at nt 1178 in exon 10 producing a Arg----His
      substitution at amino acid 393. G6PD Loma Linda had a C----A substitution at nt
      1089 in exon 10, producing a Asn----Lys change at amino acid 363. The results
      confirm our earlier results suggesting that the NADP-binding site is in a small
      region of exon 10 and suggest the possibility that this area is also concerned
      with the binding of glucose-6-P.

PMID- 1999410
TI  - Characterization of three related murine interleukin-3 surface receptor proteins.
AB  - Iodinated interleukin-3 (IL-3) can be covalently cross-linked to three specific
      surface glycoproteins with net molecular masses of 170, 140, and 65-70 kDa under
      conditions in which ligand internalization and degradation do not occur. These
      three proteins plus two additional non-ligand-binding proteins of 90 and 55 kDa
      can be purified by IL-3 affinity chromatography. Comparative two-dimensional
      analysis of the tryptic digests of these five proteins indicates that the ligand
      binding proteins are highly related at the peptide level. Incubation of cells
      with 125I-IL-3 at 37 degrees C results in rapid time- and energy-dependent
      internalization and degradation of ligand. Under these conditions only the 140-
      and 65-70-kDa binding proteins, which can recycle to the surface after
      internalization, can be identified. The lability of the 170-kDa protein indicates
      that it may not recycle. Thus, an energy-dependent mechanism is responsible for
      internalization and may be necessary for any potential interconversion of the
      higher 170- or 140-kDa proteins to the lower 140- and/or 65-70-kDa binding
      proteins.

PMID- 1999411
TI  - Conversion of pig pancreas phospholipase A2 by protein engineering into enzyme
      active against Escherichia coli treated with the bactericidal/permeability
      increasing protein.
AB  - Phospholipases A2 (PLA-2) are conserved enzymes that can vary widely in their
      activity toward certain biological targets. Activity of PLA-2 toward Escherichia
      coli treated with the bactericidal/permeability-increasing protein (BPI) of
      granulocytes has been detected only in "Group II" PLA-2 (lacking Cys11-Cys77) and
      correlates with overall basicity and the presence of a cluster of basic amino
      acids within a variable surface region near the NH2 terminus (including residues
      6, 7, 10, 11, and 15). We now show that of five pancreatic PLA-2 ("Group I"
      enzymes) tested from different species of mammals, the human enzyme that is most
      basic both globally (pI 8.7) and locally (Arg-6, Lys-7, and Lys-10) is active
      toward BPI-treated E. coli (approximately 1-2% activity of the most active Group
      II PLA-2) whereas the other four PLA-2 are essentially inactive (less than 0.1%).
      The cDNA of the pig pancreatic PLA-2 (pI 6.4; Arg-6, Ser-7, Lys-10) has been
      modified by site-specific mutagenesis and the wild-type and mutant PLA-2 have
      been expressed in and purified from either E. coli or Saccharomyces cerevisiae to
      determine more precisely the structural determinants of PLA-2 activity toward BPI
      treated E. coli. The single substitution of lysine (or arginine) for Ser-7
      transformed the pig pancreatic PLA-2 into an active enzyme toward BPI-treated E.
      coli possessing 25-50% the activity of the human PLA-2. Additional modifications
      to increase global basicity (increase in net charge up to +4) caused a further
      (up to 2-fold) increase in activity. All mutant PLA-2 still containing Ser-7
      possessed little or no activity toward BPI-treated E. coli. Changes in activity
      toward BPI-treated E. coli were accompanied by parallel changes in enzyme binding
      to this target. In contrast, substitution of lysine (or arginine) for Ser-7
      caused little or no alteration of enzyme activity toward either autoclaved E.
      coli or egg yolk lipoproteins indicating no major effects on the catalytic
      properties of the PLA-2. This study demonstrates directly the role of NH2
      terminal basic residues in the action of PLA-2 on BPI-treated E. coli and
      suggests that these properties mainly facilitate PLA-2 binding to this biological
      target.

PMID- 1999412
TI  - Structural and functional role of the amino-terminal region of porcine cytosolic
      aspartate aminotransferase. Catalytic and structural properties of enzyme
      derivatives truncated on the amino-terminal side.
AB  - In porcine cytosolic aspartate aminotransferase, a dimeric enzyme, the amino
      terminal region anchoring onto the neighboring subunit is linked to the adjoining
      floppy peptide segment (residues 12-47), an integral part of the small domain
      whose facile movement upon substrate binding is a striking "induced fit" feature
      of this enzyme. To assess the contribution by the amino-terminal region to small
      domain movement and protein stability, a series of enzyme derivatives truncated
      on the amino-terminal side (residues 1-9) was prepared by using oligonucleotide
      directed in vitro mutagenesis. Deletion of residues 1-3 showed no effect on
      catalytic activity and heat stability. Del 1-5 mutant enzyme with an extra
      methionine at position 5 showed only 43% of the kappa cat value (in the overall
      transamination) of the wild-type enzyme. Further deletion up to residue 9
      resulted in a slight decrease in kappa cat values. Del 1-9 mutant enzyme still
      retained a kappa cat value of 33% that of wild-type enzyme. Km values for
      aspartate and 2-oxoglutarate increased sharply upon deletion of residues 1-9.
      Accordingly, Del 1-9 mutant enzyme showed a striking decrease in the kappa cat/Km
      value, to only 2% of that for the wild-type enzyme. Deletion of amino-terminal
      residues 1-9 resulted also in a large decrease in thermostability and in an
      enhanced susceptibility to limited proteolysis by protease 401, which is known to
      cleave at Leu20 of the wild-type enzyme. These findings indicate that an increase
      in the conformational freedom of the floppy segment (residues 12-47) would occur
      upon the loss of most of the anchorage region, thereby presenting an entropic
      barrier to conformational changes that facilitate substrate binding with high
      affinity.

PMID- 1999414
TI  - Post-transcriptional regulation of the human liver/bone/kidney alkaline
      phosphatase gene.
AB  - Osteoblasts express high levels of liver/bone/kidney alkaline phosphatase (LBK
      AP), an enzyme critical for bone formation. Other tissues and cell types
      generally express much lower levels of LBK AP and correspondingly lower levels of
      mRNA. In light of our early observations that the human LBK AP promoter is
      expressed equally when transfected into a variety of different cells, we have
      carried out a detailed study of LBK AP gene expression in Saos-2 cells which are
      osteoblast-derived and express high levels of LBK AP mRNA, and in HepG2
      hepatoblastoma cells which express LBK AP mRNA at levels which are approximately
      1000-fold lower. Our results indicate that both of these cells utilize the same
      promoter sequences to initiate transcription of their LBK AP genes at roughly the
      same rates. Moreover, the stability of cytoplasmic LBK AP mRNA is equal in both
      cell types. The lack of any apparent buildup of unspliced precursor mRNA in the
      nucleus of HepG2 cells leads us to the conclusion that splicing (and nuclear
      export) is equivalent. It is therefore likely that differential expression is
      controlled at a very early step post-transcription, possibly by sequences that
      destabilize the nascent RNA in HepG2 cells. We reason that these destabilizing
      sequences are located in the gene's introns because a transfected LBK AP
      minigene, comprised of the full length cDNA and flanking sequences, is expressed
      efficiently in both cell types.

PMID- 1999413
TI  - Studies of ligand binding to arrestin.
AB  - A striking homology is observed between the regions 70-83 and 361-374 of the
      sequence of bovine arrestin and the calcium-binding loops of calmodulin and
      troponin C. However, the predicted alpha-helices flanking the calcium-binding
      site in calmodulin and troponin C are not present in arrestin. Direct
      measurements therefore were made in order to assess whether arrestin can bind
      calcium. We found that arrestin does not bind Ca2+ at physiological ionic
      strength, as determined by equilibrium dialysis, gel filtration, and fluorescence
      spectroscopy. Rapid and quantitative precipitation of arrestin occurs with Tb3+.
      The precipitation is reversed by EDTA and blocked by Mg2+ but not by Ca2+.
      Prompted by several reports, we also investigated whether nucleotides bind to
      arrestin. Neither ATP nor GTP binds under the conditions tested. Binding of
      arrestin to photolyzed, phosphorylated rhodopsin also does not influence the
      binding of calcium or nucleotides.

PMID- 1999415
TI  - Evidence for an essential role of long chain acyl-CoA synthetase in animal cell
      proliferation. Inhibition of long chain acyl-CoA synthetase by triacsins caused
      inhibition of Raji cell proliferation.
AB  - Triacsins A, B, C, and D are new inhibitors of long chain acyl-CoA synthetase (EC
      6.2.1.3) and possess different inhibitory potencies against the enzyme (Tomoda,
      H., Igarashi, K., and Omura, S. (1987) Biochim. Biophys. Acta 921, 595-598). Acyl
      CoA synthetase activity in the membrane fraction of Raji cells was also inhibited
      by triacsins. The same hierarchy of inhibitory potency as that against the enzyme
      from other sources, triacsin C greater than triacsin A much greater than triacsin
      D greater than or equal to triacsin B, was observed. When Raji cells were
      cultivated in the presence of triacsins, cell proliferation was inhibited in a
      dose-dependent fashion. The drug concentrations required for 50% inhibition of
      cell growth at day 2 were calculated to be 1.8 microM for triacsin A, much
      greater than 20 microM for triacsin B, 1.0 microM for triacsin C, and much
      greater than 15 microM for triacsin D, demonstrating a hierarchy for inhibitory
      potency of triacsins similar to that against the acyl-CoA synthetase activity. To
      understand the role of long chain acyl-CoA synthetase in animal cells, the effect
      of triacsins on the lipid metabolism of Raji cells was studied. When intact Raji
      cells were incubated with [14C]oleate in the presence of individual triacsins,
      the incorporation of [14C]oleate into each of the lipid fractions such as
      phosphatidylcholine, phosphatidylethanolamine, and triacylglycerol was inhibited
      to an analogous extent. A common hierarchy, triacsin C greater than triacsin A
      much greater than triacsin D greater than triacsin B, was shown for the
      inhibition in each synthesis of the three lipids, which was identical with that
      for acyl-CoA synthetase. These findings indicate that the inhibition of acyl-CoA
      synthetase is well correlated with the inhibition of lipid synthesis. Taken
      together, the data strongly suggest that the inhibition of acyl-CoA synthetase by
      triacsins leads to the inhibition of lipid synthesis and eventually to the
      inhibition of proliferation of Raji cells.

PMID- 1999416
TI  - Structure determination by 1H NMR spectroscopy of (sulfated) sialylated N-linked
      carbohydrate chains released from porcine thyroglobulin by peptide-N4-(N-acetyl
      beta-glucosaminyl)asparagine amidase-F.
AB  - The N-linked carbohydrate chains of porcine thyroglobulin were released by
      peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase-F (PNGase-F). The
      resulting oligosaccharides were fractionated by a combination of fast protein
      liquid chromatography and high performance liquid chromatography and analyzed by
      500-MHz 1H NMR spectroscopy. The major acidic compounds are mono- and
      disialylated, fucosylated diantennary compounds terminated with alpha(2-6)-linked
      sialic acid on the Man alpha(1-3) branch. The Man alpha(1-6) branch shows a large
      heterogeneity. It can be terminated with Man-4', GlcNAc-5', or Gal-6', whereas
      the Gal-6' residue may be extended with Gal alpha(1-3), NeuAc alpha(2-3), or Sia
      alpha (2-6). In the major structures 8% of alpha(2-6)-linked sialic acid was
      found as NeuGc instead of NeuAc. The main compounds have sulfated homologues
      bearing a sulfate group (6-20%) at C-3 of Gal-6' or at C-6 of GlcNAc-5 as
      follows. [formula: see text]

PMID- 1999418
TI  - Biological recognition of phosphate and sulfate.
AB  - The biological recognition of trigonal pyramids has been studied in a statistical
      analysis of the Cambridge Structural Data Base. The preferential stereochemistry
      of pyramidal anion-Lewis acid interactions is easily described for the phosphonyl
      dianion (R-PO3(2-), as found in the phosphate group) and the sulfonyl monoanion
      (R-SO3-, as found in the sulfate group) by trans/gauche conformational
      terminology. Interactions between these pyramidal anions and metals generally
      prefer gauche geometry (as defined by the R-X = O-Mn+ torsion angle, X = P or S).
      Interactions between phosphonyls and hydrogen bond donors likewise display a
      preference for gauche orientation. Interactions between sulfonyls and hydrogen
      bond donors exhibit a preference for gauche stereochemistry and also cluster in
      eclipsed regions. These hydrogen bond motifs provide a greater understanding of
      the function of pyramidal anions in biological structure and function. For
      example, interactions of the sulfate monoanion are important for the binding of
      heparin, a sulfated glycosaminoglycan, to antithrombin III.

PMID- 1999417
TI  - Isolation of the cDNA encoding glycoprotein-2 (GP-2), the major zymogen granule
      membrane protein. Homology to uromodulin/Tamm-Horsfall protein.
AB  - GP-2, a 78-kDa glycoprotein, is the major component of zymogen granule membranes
      of the exocrine pancreas. We report the isolation of the cDNA encoding for GP-2
      from a rat pancreatic lambda gt-11 cDNA library. The cDNA is 1921 base pairs in
      length with an open reading frame encoding for a protein of 530 amino acids
      containing eight potential N-glycosylation sites. It encompasses the amino
      terminus of the protein including the signal sequence as evidenced by in vitro
      transcription/translation experiments conducted in the presence of dog pancreas
      rough microsomes in which the protein underwent apparent core glycosylation. A
      hydrophobic stretch of amino acids is present at the carboxyl terminus which is
      likely to serve as a signal for attachment of a glycosyl phosphatidylinositol
      (GPI) membrane anchor as has been described for GP-2. When the cDNA was
      introduced into HeLa cells by transfection, the expressed protein was located on
      the cell surface and could be released by incubation of the cells with
      phosphatidylinositol-specific phospholipase C, confirming that it is GPI-linked.
      Upon searching through the GenBank database, the GP-2 amino acid sequence was
      found to have a 53% identity and 85% similarity to human uromodulin/Tamm-Horsfall
      protein (THP) over a 450-amino acid stretch that encompassed all 28 cysteines
      after the signal sequence of GP-2. Uromodulin/Tamm-Horsfall protein, an 85-kDa
      glycoprotein synthesized by the kidney, shares several characteristics with GP-2
      in addition to its sequence similarity. Both are attached to the membrane by a
      GPI anchor, but are also released from the apical surface of their respective
      cells and subsequently form large aggregates. Together they may define a new gene
      family.

PMID- 1999419
TI  - Mapping of the amino acids in membrane-embedded helices that interact with the
      retinal chromophore in bovine rhodopsin.
AB  - By using a photoactivatable analog of 11-cis-retinal in rhodopsin, we have
      previously identified the amino acids Phe-115, Ala-117, Glu-122, Trp-126, Ser
      127, and Trp-265 as major sites of cross-linking to the chromophore. To further
      investigate the amino acids that interact with retinal, we have now used site
      directed mutagenesis to replace a variety of amino acids in the membrane-embedded
      helices in bovine rhodopsin, including those that were indicated by cross-linking
      studies. The mutant rhodopsin genes were expressed in monkey kidney cells (COS-1)
      and purified. The mutant proteins were studied for their spectroscopic properties
      and their ability to activate transducin. Substitution of the two amino acids,
      Trp-265 and Glu-122 by Tyr, Phe, and Ala and by Gln, Asp and Ala, respectively,
      resulted in blue-shifted (20-30 nm) chromophore, and substitution of Trp-265 by
      Ala resulted in marked reduction in the extent of chromophore regeneration. Light
      dependent bleaching behavior was significantly altered in Ala-117----Phe, Trp-265
      ---Phe, Ala, and Ala-292----Asp mutants. Transducin activation was reduced in
      these mutants, in particular Trp-265 mutants, as well as in Glu-122----Gln, Trp
      126----Leu (Ala), Pro-267----Ala (Asn, Ser), and Tyr-268----Phe mutants. These
      findings indicate that Trp-265 is located close to retinal and Glu-122, Trp-126,
      and probably Tyr-268 are also likely to be near retinal.

PMID- 1999420
TI  - Monolayers of long chain lecithins at the air/water interface and their
      hydrolysis by phospholipase A2.
AB  - The behavior of phosphatidylcholine monolayers at the air/water interface was
      studied by measuring their surface isotherm, surface potential, surface
      viscosity, and rate of hydrolysis by the dimeric phospholipase A2 from the venom
      of Crotalus atrox. The monolayers showed typical liquid-expanded behavior. In
      this phase, the surface potential was linearly dependent on surface concentration
      and extrapolated at zero concentration to a value characteristic of a liquid
      hydrocarbon/water interface. The rate of the reaction was measured by monitoring
      changes in area at constant surface pressure for 1,2-dioctanoyl- and 1,2
      didecanoyl-3-sn-phosphatidylcholines, and by monitoring changes in surface
      potential for 1,2-dimyristoyl-, 1,2-dipalmitoyl-, 1-palmitoyl-2-oleoyl-, and 1
      oleoyl-2-palmitoyl-sn-glycero-3-phosphocholines. The enzymatic hydrolysis is
      first order with respect to the enzyme-calcium complex which forms with a Kd =
      1.5 mM. A mechanism is proposed to account for the dependency of the reaction
      rates on the surface concentration of the substrate. We postulate that the rate
      limiting step is the decomposition of a quaternary complex formed from two
      phospholipid molecules, one calcium ion and one dimeric enzyme. The rate is
      independent of the surface pressure per se; addition of inert lipids to a
      monolayer at constant area, and hence constant surface concentration of the
      substrate, increases the surface pressure without changing the surface density of
      the substrate yielding maximal enzymatic rate. The enzyme is specific for loosely
      packed substrate molecules in the liquid-expanded state: transition into the
      liquid-condensed state or compression of the liquid-expanded layer beyond 80
      A2/phospholipid strongly inhibits the enzymatic reaction. Our results show that
      surface recognition is a direct consequence of a bifunctional active site since
      it is only at a phospholipid surface that the distance between two substrate
      molecules is optimal for forming a catalytically competent enzyme-Ca2+
      (substrate)2 complex.

PMID- 1999421
TI  - Trafficking of lipids from the endoplasmic reticulum to the Golgi apparatus in a
      cell-free system from rat liver.
AB  - Trafficking and sorting of lipids during transport from the endoplasmic reticulum
      to the Golgi apparatus was studied using a cell-free system from rat liver.
      Transitional elements of the endoplasmic reticulum were prepared from liver
      slices prelabeled with [14C]- or [3H]acetate as the donor fraction. Non
      radioactive Golgi apparatus were immobilized on nitrocellulose as the acceptor.
      When reconstituted, the radiolabeled donor retained a capacity to transfer
      labeled lipids to the non-radioactive Golgi apparatus acceptor. Transfer
      exhibited two kinetically different components. One was stimulated by ATP,
      facilitated by cytosol and inhibited by guanosine 5'-O-(thiotriphosphate) and N
      ethylmaleimide. In parallel with protein transport, the ATP-dependent lipid
      transfer occurred with a temperature transition at about 20 degrees C. The other
      was not stimulated by ATP, did not require cytosol, was acceptor unspecific, was
      unaffected by inhibitors and, while temperature dependent, did not exhibit a
      sharp temperature transition. The ATP-independent transfer was non-vesicular. In
      contrast, the ATP-dependent transfer was vesicular. Transition vesicles isolated
      by preparative free-flow electrophoresis, when used as the donor fraction,
      transferred lipids to Golgi apparatus acceptor with a 5-6-fold greater efficiency
      than that exhibited by the unfractionated transitional endoplasmic reticulum.
      Formation of transition vesicles was ATP-dependent. Transferred lipids were
      chiefly phosphatidylcholine and cholesterol. Membrane triglycerides, major
      constituents of the transitional endoplasmic reticulum membranes, were both
      depleted in the transition vesicle-enriched fractions and not transferred to
      Golgi apparatus suggestive of lipid sorting prior to or during transition vesicle
      formation. The characteristics of the ATP plus cytosol-dependent transfer were
      similar to those for protein transfer mediated by transition vesicles. Thus, the
      50-70-nm vesicles derived from transitional endoplasmic reticulum appear to
      function in the trafficking of both newly synthesized proteins and lipids from
      the endoplasmic reticulum to the Golgi apparatus.

PMID- 1999422
TI  - Cell-free transfer of membrane lipids. Evidence for lipid processing.
AB  - A latent phospholipase A is concentrated in cis elements of rat liver Golgi
      apparatus, the presumed sites of fusion of the 50-70-nm transition vesicles
      formed from endoplasmic reticulum. As a result, conversion of transferred
      phospholipids to their corresponding lysoforms may provide an index of post
      transfer lipid processing in a corresponding reconstituted membrane transfer
      system. To label the phosphatidylcholine of transitional endoplasmic reticulum in
      vitro, [14C]CDP-choline and endogenous cytidyltransferases were used. In the
      reconstituted transfer system, the radiolabeled phosphatidylcholine was
      transferred via transition vesicles to Golgi apparatus immobilized on
      nitrocellulose strips in a time- and temperature-dependent process. Transfer was
      promoted by ATP and the ATP-dependent transfer was specific for cis Golgi
      apparatus elements as acceptor. Trans Golgi apparatus elements were ineffective
      as acceptors. Median Golgi apparatus elements were intermediate. A portion of the
      transferred phosphatidylcholine was converted subsequently to
      lysophosphatidylcholine also in a time- and ATP-dependent manner. The
      phospholipase A activity of the Golgi apparatus was more than 90% latent (active
      site located on the lumens of the Golgi apparatus membranes). Therefore, the
      lipid-containing vesicles derived from endoplasmic reticulum must have combined
      with cis Golgi apparatus membranes as the basis for Golgi apparatus-dependent
      phospholipase A processing of endoplasmic reticulum-derived phosphatidylcholine.
      Since the lipids were processed by phospholipase A in approximately the same
      proportion as occurs in situ, the findings offer evidence both for the
      specificity of the ATP-dependent component of cell-free lipid transfer from
      endoplasmic reticulum to Golgi apparatus and its fidelity to lipid transfer
      observed in vivo.

PMID- 1999423
TI  - Clathrin assembly protein AP-3. The identity of the 155K protein, AP 180, and
      NP185 and demonstration of a clathrin binding domain.
AB  - Three independently isolated clathrin-associated proteins have been reported that
      have molecular weights of approximately 155,000-185,000 on sodium dodecyl sulfate
      polyacrylamide gel electrophoresis: the 155K protein (Keen, J. H., and Black, M.
      M. (1986) J. Cell Biol. 102, 1325-1333), AP 180 (Ahle, S., and Ungewickell, E.
      (1986) EMBO J. 5, 3143-3149), and NP185 (Kohtz, D. S., and Puszkin, S. (1988) J.
      Biol. Chem. 263, 7418-7425). Using two-dimensional isoelectric focusing
      polyacrylamide gel electrophoresis and one- and two-dimensional immunoblots with
      two different monoclonal antibodies, we show that these three proteins are
      identical. The term AP-3 is used to denote this protein. A preliminary analysis
      of the domain structure of AP-3 was done by controlled proteolysis. Trypsin
      treatment of AP-3 yields two distinct classes of products. The larger fragments
      obtained (100,000-135,000 apparent Mr) are acidic and behave anomalously on gel
      electrophoresis, yielding aberrantly high Mr and exhibiting poor dye binding;
      these characteristics are shared with intact AP-3. Trypsin also generates a
      smaller neutral species of approximately 30,000 Da which migrates appropriately
      on sodium dodecyl sulfate-gel electrophoresis, binds dye comparatively strongly,
      and behaves as a monomeric globular species in solution. In addition, this
      species, which is also released by a variety of other proteases, binds
      specifically and reversibly to clathrin-Sepharose, identifying it as a clathrin
      recognition domain.

PMID- 1999424
TI  - Transcriptional regulation of ribosomal RNA synthesis during growth of cardiac
      myocytes in culture.
AB  - The mechanism(s) by which rRNA accumulates during the growth of cardiac myocytes
      was investigated. The rates of rDNA transcription were measured in contracting
      myocytes and compared with nonbeating myocytes depolarized with 50 mM KCl. After
      3 days of contraction the absolute rate of rDNA transcription was accelerated by
      2-fold as measured by incorporation of [3H]UTP into the external transcribed
      spacer of preribosomal RNA. Corresponding increases in transcription were
      observed in isolated nuclei of contracting myocytes as measured by either
      hybridization of run-on transcripts of preribosomal RNA or activity of RNA
      polymerase I. The extent to which transcription was stimulated in contracting
      myocytes accounted for the previously observed acceleration of rRNA synthesis
      rates. The steady-state levels of preribosomal RNA relative to rRNA were
      unchanged in contracting myocytes, but the total amount of preribosomal RNA was
      1.3-fold greater as a result of increased rRNA content. The increase of
      preribosomal RNA in proportion to rRNA in contracting myocytes demonstrated that
      the rate of preribosomal RNA processing was unchanged and that rRNA synthesis is
      regulated by an accelerated rate of rDNA transcription.

PMID- 1999425
TI  - Genetic and biochemical characterization of Cu,Zn superoxide dismutase mutants in
      Saccharomyces cerevisiae.
AB  - The allele scd 1 is a recessive chromosomal mutation in Saccharomyces cerevisiae
      that eliminates Cu,Zn superoxide dismutase (SOD-1) activity. SOD-1- strains are
      unable to grow in 100% O2 in rich medium and are methionine and lysine
      auxotrophic when grown in air (Bilinski, T., Krawiec, Z., Liczmanski, A., and
      Litwinska, J. (1985) Biochem. Biophys. Res. Commun. 130, 533-539). In this
      report, scd1 was genetically mapped to the right arm of chromosome X, 11
      centimorgans proximal to cdc11. The gene for SOD-1 (SOD1) was physically mapped
      by Southern blot to restriction fragments containing CDC11. scd1 failed to
      complement a complete deletion of SOD1. Thus, scd1 maps to the SOD1 locus and is
      designated sod1-1. The molecular basis for the lack of SOD-1 activity in sodl-1
      carrying strains has also been established. The size and amount of SOD-1 mRNA in
      the mutant were essentially the same as in wild type cells. Western blot analysis
      showed that the SOD-1 dimer and 16-kilodalton subunit that co-migrated
      electrophoretically with wild type yeast SOD-1 were abundant in mutant cell
      extracts. However, two additional SOD-1 immunoreactive polypeptides were detected
      in these extracts in both denaturing and nondenaturing gels. None of the SOD-1
      immunoreactive species in the mutant extracts exhibited superoxide dismutase
      activity. Transformants of the mutant strain carrying episomal, wild type SOD1
      expressed wild type, active SOD-1 protein, indicating that the mutant allele had
      no discernible effect on the correct synthesis and activation of apoSOD-1. Size
      exclusion chromatography of soluble cell extracts derived from wild type and SOD1
      deletion strains identified a copper binding peak that corresponded to SOD-1.
      This copper-binding fraction was absent in cell extracts from the sod1-1
      containing strain although Western blot analysis of the corresponding
      chromatographic fractions showed that SOD-1 polypeptide was present in these
      fractions. Sequence data derived from the cloned genes showed that sod1-1
      differed from SOD1 only in the adjacent 5'-noncoding region. The biochemical data
      indicate that this genetic alteration results in the synthesis of a collection of
      SOD-1 polypeptides that fail to bind copper and may also fail to completely self
      associate. Both phenotypes could be due to the inability of these polypeptides to
      adopt the native SOD-1 conformation.

PMID- 1999426
TI  - Isolation of BamHI variants with reduced cleavage activities.
AB  - Derivation of the bamhIR sequence (Brooks, J. E., Nathan, P.D., Landry, D.,
      Sznyter, L.A., Waite-Rees, P., Ives, C. C., Mazzola, L. M., Slatko, B. E., and
      Benner, J. S. (1991) Nucleic Acids Res., in press), the gene coding for BamHI
      endonuclease, has facilitated construction of an Escherichia coli strain that
      overproduces BamHI endonuclease (W. E. Jack, L. Greenough, L. F. Dorner, S. Y.
      Xu, T. Strezelecka, A. K. Aggarwal, and I. Schildkraut, submitted for
      publication). As expected, low-level constitutive expression of the bamhIR gene
      in E. coli from the Ptac promotor construct is lethal to the host unless the
      bamHIM gene, which encodes the BamHI methylase, is also expressed within the
      cell. We identified four classes of BamHI endonuclease variants deficient in
      catalysis by selecting for survival of a host deficient for bamHIM gene,
      transformed with mutagenized copies of the bamhIR gene, and then screening the
      surviving cell extracts for DNA cleavage and binding activities. Class I variants
      (G56S, G91S/T153I, T114I, G130R, E135K, T153I, T157I, G194D) displayed 0.1-1% of
      the wild-type cleavage activity; class II variant (D94N) lacked cleavage activity
      but retained wild-type DNA binding specificity; class III variants (E77K, E113K)
      lacked cleavage activity but bound DNA more tightly; class IV variants (G56D,
      G90D, G91S, R122H, R155H) lacked both binding and cleavage activities. Variants
      with residual cleavage activities induced the E. coli SOS response and thus are
      presumed to cleave chromosomal DNA in vivo. We conclude that Glu77, Asp94, and
      Glu113 residues are essential for BamHI catalytic function.

PMID- 1999427
TI  - Modification of low density lipoproteins by secretory granules of rat serosal
      mast cells.
AB  - When low density lipoprotein (LDL) is incubated with granules isolated from rat
      serosal mast cells, a fraction of LDL is bound to the granule heparin
      proteoglycan. If incubation is continued at 37 degrees C, the bound LDL, but not
      the unbound LDL, is degraded by granule neutral proteases. In the early stage of
      incubation, all the granule-bound LDL can be released by 0.3 M NaCl (the "salt
      sensitive" fraction of LDL). With time, an increasing proportion of the granule
      bound LDL requires 0.5 M NaCl for release (the "salt-resistant" fraction of LDL).
      Chemical analysis showed that, on average, 20% of the apolipoprotein B LDL was
      lost from the salt-sensitive fraction and 60% from the salt-resistant fraction,
      without any change in the composition of the lipid portion. Electron microscopic
      analysis disclosed large fused particles of LDL (diameters up to 100 nm) in the
      highly proteolyzed salt-resistant fraction, but no fused particles could be found
      in the less proteolyzed salt-sensitive fraction. We conclude that both binding
      and extensive degradation of LDL by mast cell granules is required for fusion of
      LDL particles on the granule surface. As compared with native LDL, the mast cell
      granule-modified LDL particles exhibit (i) increased particle size, (ii)
      selective loss of protein (apoB), (iii) a decrease in hydrated density, and (iv)
      stronger ionic interaction between apoB and heparin proteoglycan. The particles
      resemble the extracellular lipid droplets found in atherosclerotic lesions of
      both man and animals. Modification of LDL by mast cells may therefore provide a
      model of how these lipid structures are formed.

PMID- 1999428
TI  - Purification to apparent homogeneity by immunoaffinity chromatography and partial
      characterization of the GM3 ganglioside-forming enzyme, CMP-sialic
      acid:lactosylceramide alpha 2,3-sialyltransferase (SAT-1), from rat liver Golgi.
AB  - CMP-sialic acid:lactosylceramide alpha 2,3-sialyltransferase (SAT-1) has been
      purified approximately 40,000-fold to apparent homogeneity from rat liver Golgi.
      The enzyme was solubilized from Golgi vesicles in 5% lauryldimethylamine oxide
      and "partially" purified by affinity chromatography twice on CMP-hexanolamine and
      once on lactosylceramide aldehyde-Sepharose 4B. Final purification was achieved
      by immunoaffinity chromatography on M12GC7-Gel 10. The M12GC7 monoclonal antibody
      specifically inhibits and immunoprecipitates SAT-1 activity. Identification of
      the protein, with an apparent molecular weight by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis of about 60,000 daltons, was confirmed by
      Western blot and immunodetection with M12GC7. SAT-1 specifically catalyzes the
      transfer of N-acetylneuraminic acid (NeuAc, sialic acid) to lactosylceramide (Gal
      beta 1-4Glc beta 1-O-ceramide), forming GM3 ganglioside. Studies on substrate
      specificity indicate that the preferred acceptors have the general structure
      saccharide beta 1-O-ceramide, a disaccharide being preferred to a monosaccharide.
      SAT-1 is a glycoprotein. The carbohydrate moieties are detected with specific
      lectins. Deglycosylation of SAT-1 with N-glycanase results in an increase in a
      43,000-dalton band. The two-dimensional electrophoretogram of SAT-1 indicates a
      pI range of 5.7-6.2 for the 60,000-dalton protein.

PMID- 1999429
TI  - Biosynthesis of phosphatidylinositol glycan-anchored membrane proteins. Design of
      a simple protein substrate to characterize the enzyme that cleaves the COOH
      terminal signal peptide.
AB  - Many nascent proteins that are destined to be anchored to plasma membranes by a
      phosphatidylinositol glycan (PI-G) are in the range of 50-70 kDa so that changes
      of 2-3 kDa between precursors and products during processing are not easily
      detected. Furthermore, PI-G-anchored proteins are generally glycosylated so that
      changes between the nascent (prepro) proteins and the mature products are not due
      simply to the loss of signal peptides. These problems have made it difficult to
      monitor the processing of the prepro form of wild type human placental alkaline
      phosphatase (PLAP) in a cell-free system. We have designed a smaller and simpler
      substrate of PI-G "transamidase" derived by deletion of approximately 60% of the
      internal sequence of preproPLAP 513. This engineered protein, preprominiPLAP 208,
      retains the NH2- and COOH-terminal signal peptides of PLAP as well as all the
      epitopes for site-directed antibodies of the latter, but is devoid of
      glycosylation sites, the active site, and most of the cysteine residues. With
      preprominiPLAP, it has been possible to demonstrate, in a cell-free system, step
      by step conversion to the pro form and then to the mature form, with the
      concomitant loss of the appropriate signal peptides. These changes were shown to
      be time- and enzyme concentration-dependent. Studies with Asp-179 site-directed
      mutants of preprominiPLAP showed the same specificity for amino acids with a
      monosubstituted beta carbon at the cleavage/attachment site that were found
      previously with wild type PLAP.

PMID- 1999430
TI  - Defective brush-border expression of intrinsic factor-cobalamin receptor in
      canine inherited intestinal cobalamin malabsorption.
AB  - Ligand binding activity of intrinsic factor-cobalamin receptor (IFCR) was
      determined in homogenates and isolated brush-border membranes (BBM) of ileum and
      kidney from dogs exhibiting simple autosomal recessive inheritance of selective
      cobalamin malabsorption (Fyfe, J. C., Giger, U., Hall, C. A., Jezyk, P. F.,
      Klumpp, S. A., Levine, J. S., and Patterson, D. F. (1991) Pediatr. Res. 29, 24
      31). IFCR activity of affected dog ileal homogenates was 3-4-fold higher than
      normal whereas IFCR activity in affected dog kidney homogenates was one-tenth of
      normal. The recovery of IFCR activity in the BBM of ileum and renal cortex of
      affected dogs was 30- and 20-fold less than normal, respectively. The
      dissociation constant (Kd) for intrinsic factor-cobalamin was similar in BBM of
      both tissues and was the same in affected and normal dogs. In the affected dog
      ileal BBM, activities of alkaline phosphatase and sucrase-isomaltase and
      vesicular transport of glucose and Na(+)-taurocholate were normal. Immunoblots
      showed no IFCR cross-reactive material in the ileal or renal BBM of affected
      dogs. IFCR purified by affinity chromatography from kidney of both normal and
      affected dogs had an Mr = 230,000. However, amino acid analysis revealed that the
      affected dog IFCR had more lysine than the normal, and protease cleavage of the
      purified IFCRs revealed different peptide maps. Asparagine-linked
      oligosaccharides of both proteins were sensitive to peptide N-glycosidase F
      cleavage, but only the affected dog IFCR was endoglycosidase H sensitive. These
      results suggest that cobalamin malabsorption in this canine family is caused by
      inefficient BBM expression of IFCR due to a mutation of IFCR and its retention in
      an early biosynthetic compartment.

PMID- 1999431
TI  - The alpha 1 (VIII) collagen gene is homologous to the alpha 1 (X) collagen gene
      and contains a large exon encoding the entire triple helical and carboxyl
      terminal non-triple helical domains of the alpha 1 (VIII) polypeptide.
AB  - We recently cloned and sequenced alpha 1 (VIII) collagen cDNAs and demonstrated
      that type VIII collagen is a short-chain collagen that contains both triple
      helical and carboxyl-terminal non-triple helical domains similar to those of type
      X collagen (Yamaguchi, N., Benya, P., van der Rest, M., and Ninomiya, Y. (1989)
      J. Biol. Chem. 264, 16022-16029). We report here on the structural organization
      of the gene encoding the rabbit alpha 1 (VIII) collagen chain. The alpha 1 (VIII)
      gene contains four exons, whose sizes are 69, 120, 331, and 2278 base pairs. The
      first and second exons encode only 5'-untranslated sequences, whereas the third
      exon codes for a very short (3 nucleotides) stretch of 5'-untranslated sequence,
      the signal peptide, and almost the entire amino-terminal non-triple helical (NC2)
      domain (109 1/3 codons). Interestingly, the last exon encodes the rest of the
      translated region, including 7 2/3 codons of the NC2 domains, the complete triple
      helical domain (COL1, 454 amino acid residues), the entire carboxyl-terminal non
      triple helical domain (NC1, 173 amino acid residues), and the 3'-untranslated
      region. This exon-intron structure is in stark contrast to the multi-exon
      structure of the fibrillar collagen (types I, II, III, V, and XI) genes, but it
      is remarkably similar to that of the type X collagen gene (LuValle, P., Ninomiya,
      Y., Rosenblum, N. D., and Olsen, B. R. (1988) J. Biol. Chem. 263, 18278-18385).
      The data suggest that the alpha 1 (VIII) and the alpha 1 (X) genes belong to the
      same subclass within the collagen family and that they arose from a common
      evolutionary precursor.

PMID- 1999432
TI  - Purification of a 92-kDa cytoplasmic protein tightly associated with the cell
      cell adhesion molecule E-cadherin (uvomorulin). Characterization and
      extractability of the protein complex from the cell cytostructure.
AB  - The transmembrane epithelial cell-cell adhesion protein E-cadherin (uvomorulin)
      associates via its cytoplasmic domain with three or more proteins whose structure
      and function are not yet established. The associated proteins, also termed
      catenins (Ozawa, M., Baribault, H., and Kemler, R. (1989) EMBO J. 8, 1711-1717),
      are of interest because they may form a link to the cytoskeleton, and/or regulate
      E-cadherin function. In this report immunoprecipitates of E-cadherin complexes,
      isolated from Xenopus laevis A6 and Madin-Darby canine kidney cell monolayers,
      were stringently washed to leave a single very tightly associated protein of
      approximately 92 kDa. We report on the 92-kDa protein's association with E
      cadherin in the presence of various perturbants, its preferential dissociation
      from the immune complex upon exposure to mixed detergent micelles containing
      sodium dodecyl sulfate, and its preparative purification to homogeneity. We have
      additionally found that E-cadherin and its associated proteins may be easily and
      quantitatively extracted from both subconfluent and fully confluent cells by a
      variety of mild nonionic detergents made up in isotonic buffers. In contrast,
      such extractions at short times left most of the cytoskeletal protein fodrin in
      the insoluble pellet fraction. Western blots of immunoprecipitated E-cadherin
      complexes failed to detect the presence of fodrin, or that of the cytoskeletal
      proteins adducin, alpha-actinin, and vinculin. If the E-cadherin-associated
      protein complex interacts with known proteins of the cell cytoskeleton, such
      interactions are labile and/or transient.

PMID- 1999433
TI  - Expression of normal and novel glucokinase mRNAs in anterior pituitary and islet
      cells.
AB  - The glucose-phosphorylating enzyme glucokinase likely plays an important role in
      regulating glucose-stimulated insulin secretion from the islets of Langerhans and
      has previously been thought to be expressed only in that tissue and in liver. In
      this study, we demonstrate high levels of glucokinase mRNA in the anterior
      pituitary cell line AtT20ins, which has been engineered to secrete correctly
      processed insulin, as well as in primary anterior pituitary tissue. Unlike islet
      or liver cells, expression of glucokinase mRNA in anterior pituitary cells was
      not accompanied by expression of the high Km glucose transporter (GLUT-2) mRNA.
      The glucokinase transcript in anterior pituitary cells was similar in size to
      islet glucokinase mRNA, which has a unique, elongated 5'-end relative to the
      liver glucokinase message. Amplification and sequence analysis of the glucokinase
      mRNA expressed in islets, RIN1046-38 cells, and anterior pituitary cells
      confirmed that the glucokinase transcripts in these cell types contain the same
      5'-sequence. In addition, a novel alternative transcript was identified that
      contains a 52-nucleotide deletion and that predicts a 58-amino acid peptide as a
      result of a frame shift. Both the deleted and undeleted transcripts were found in
      islets, RIN cells, and AtT20ins cells, whereas only the deleted product was
      identified in primary anterior pituitary tissue. An antibody prepared against a
      peptide found at the N terminus of the islet isoform of glucokinase easily
      detected a protein with a size predicted by the undeleted transcript in extracts
      prepared from islets, RIN1046-38 cells, and AtT20ins cells. Since both the
      glucokinase protein and mRNA are naturally expressed in AtT20ins and RIN1046-38
      cells, we compared the effect of varying concentrations of glucose on insulin
      secretion from the two lines. Insulin secretion from RIN1046-38 cells was
      stimulated by glucose in a dose-dependent manner over the range 0-2.5 mM, where
      it reached a maximum. AtT20ins cells, in contrast, exhibited no response to
      glucose at any concentration tested, despite the fact that insulin secretion from
      both cell lines was stimulated by incubation with dibutyryl cAMP. We conclude
      that glucokinase expression in AtT20ins cells may be necessary, but is not
      sufficient to confer glucose-stimulated insulin secretion.

PMID- 1999434
TI  - A specific type of ganglioside as a modulator of insulin-dependent cell growth
      and insulin receptor tyrosine kinase activity. Possible association of
      ganglioside-induced inhibition of insulin receptor function and monocytic
      differentiation induction in HL-60 cells.
AB  - Insulin-dependent cell growth has been correlated with insulin receptor function,
      particularly receptor-associated kinase activity, in in vitro studies. The
      insulin-dependent phosphorylation of the 95-kDa receptor subunit was clearly
      inhibited, in a concentration-dependent manner, by the presence of unbranched
      neolacto series gangliosides having a NeuAc2----3Gal terminus, particularly 2---
      3-sialosylparagloboside (2----3SPG; IV3NeuAc-nLc4), but not by other gangliosides
      with a NeuAc2----6Gal terminus or by branched neolacto series gangliosides (e.g.
      G10). Such inhibition of phosphorylation was minimal with ganglio series
      gangliosides and negligible with sphingosine, neutral glycolipids, or sulfatide.
      2----3SPG did not affect insulin binding to the insulin receptor. Insulin
      dependent cell growth and its inhibition by 2----3SPG were observed in three
      human cell lines so far tested: lymphoid cell line IM9, promyelocytic leukemia
      cell line HL-60, and erythroleukemia cell line K562. Since IM9 cells contain a
      much higher quantity of insulin receptor than do HL-60 or K562 cells, insulin
      dependent receptor phosphorylation and its inhibition by 2----3SPG in intact
      cells were clearly observed with IM9 cells. Receptor phosphorylation in intact
      cells was inhibited when cells were preincubated in the presence of 2----3SPG.
      Insulin-dependent growth of HL-60 and K562 cells was also inhibited by prolonged
      culture (96-144 h) with exogenous 2----3SPG. Subsequent to the inhibition of
      insulin-dependent HL-60 cell growth, a remarkable phenotypic transformation was
      observed, i.e. changes in morphology, enzymes, and cell-surface markers to those
      characteristic of monocytes. The level of 2----3SPG in HL-60 cells increased when
      cells were cultured with 1 alpha,25-dihydroxyvitamin D3 to the same degree seen
      in cells cultured with 5 microM 2----3SPG. Both these treatments led to
      inhibition of insulin-dependent cell growth, followed by induction of monocytic
      differentiation. Thus, the cellular level of 2----3SPG may modulate insulin
      dependent cell growth and define the lineage specificity of differentiation
      through modulation of receptor-associated kinase activity.

PMID- 1999436
TI  - Identification of proteins involved in intracellular copper metabolism. Low
      levels of a approximately 48-kDa copper-binding protein in the brindled mouse
      model of Menkes disease.
AB  - Little is known about copper metabolism at the cellular level. The brindled mouse
      is an animal model of Menkes disease which is an inborn error of copper
      metabolism. Control and brindled mice were used to identify copper-binding
      proteins with possible roles in normal copper metabolism that are affected by the
      defect in the brindled mice. When 64Cu-labeled hepatic or renal cytosols from
      control mice were applied to Mono Q or Superose columns, a approximately 48-kDa
      protein coeluted with the protein fractions which contained the radiolabeled
      copper. Large decreases in copper binding were detected in these fractions from
      the brindled mice. The same column fractions which showed decreased copper
      binding showed large decreases in the levels of the approximately 48-kDa protein.
      Decreased copper binding and approximately 48-kDa protein were not simply
      secondary to the abnormal hepatic and renal copper levels that are found in the
      brindled mice since although their liver copper levels are low, their kidney
      copper levels are high. Elevated levels of an approximately 80-kDa heat shock
      protein were also detected in the hepatic and renal cytosols from the brindled
      mice. Consistent with expression of the primary defect in both the liver and
      kidney, the levels of the approximately 48- and approximately 80-kDa proteins
      were affected similarly in both organs. Irrespective of how the low levels of the
      approximately 48-kDa protein may be related to the basic defect in the brindled
      mice, the data are consistent with an important role for the approximately 48-kDa
      protein in intracellular copper metabolism.

PMID- 1999435
TI  - Escherichia coli DNA polymerase II is stimulated by DNA polymerase III holoenzyme
      auxiliary subunits.
AB  - DNA polymerase III of Escherichia coli requires multiple auxiliary factors to
      enable it to serve as a replicative complex. We demonstrate that auxiliary
      components of the DNA polymerase III holoenzyme, the gamma delta complex and beta
      subunit, markedly stimulate DNA polymerase II on long single-stranded templates.
      DNA polymerase II activity is enhanced by single-stranded DNA binding protein,
      but the stimulation by gamma delta and beta can be observed either in the absence
      or presence of single-stranded DNA binding protein. In contrast with DNA
      polymerase III, the requirement of DNA polymerase II for gamma delta cannot be
      bypassed by large excesses of the beta subunit at low ionic strength in the
      absence of the single-stranded DNA binding protein. The product of the DNA
      polymerase II-gamma delta-beta reaction on a uniquely primed single-stranded
      circle is of full template length; the reconstituted enzyme apparently is
      incapable of strand displacement synthesis. The possible biological implications
      of these observations are discussed.

PMID- 1999437
TI  - Site-directed mutagenesis of rat cellular retinol-binding protein. Alteration in
      binding specificity resulting from mutation of glutamine 108 to arginine.
AB  - Cellular retinol-binding protein (CRBP) is a retinol-specific binding protein. A
      rat cDNA clone of CRBP was expressed in Escherichia coli. In order to determine
      amino acid residues in CRBP which may be important for the binding of all-trans
      retinol, comparative model-building studies were performed in which strong
      sequence similarities were identified between CRBP and several other binding
      proteins. Based on this analysis, specific amino acids were predicted to be
      important in retinol binding, and these predictions were tested using the
      technique of site-directed mutagenesis to subtly alter the protein's structure
      and function. Specifically, site-directed mutagenesis was performed to alter the
      Gln-108 to Arg-108 (Q108R). Making use of fluorescence, Q108R was found to have a
      3-fold lower affinity for all-trans-retinol, and the fine structure of the
      excitation spectrum of the Q108R.all-trans-retinol complex was also different
      than for the wild type.all-trans-retinol complex. The mutant bound 13-cis-retinol
      with an excitation spectrum identical to wild type bound to 13-cis-retinol, but
      with only one-half of the fluorescence intensity. In competition binding
      experiments, the Q108R mutant was found to have similar binding affinities for
      all-trans-retinol, all-trans-retinoic acid, 13-cis-retinoic acid, and retinal,
      while wild type CRBP was only able to bind to all-trans-retinol. Thus, altering a
      single amino acid in CRBP (Gln-108 to Arg-108) caused a significant change in the
      ligand binding specificity of the protein.

PMID- 1999438
TI  - Mammalian adipose tissue and muscle are major sources of lipid transfer protein
      mRNA.
AB  - The plasma cholesteryl ester transfer protein (CETP) catalyzes the transfer of
      cholesteryl esters from high density lipoproteins (HDL) to triglyceride-rich
      lipoproteins and plays a major role in the catabolism of HDL. Lipoprotein lipase
      (LPL) is the rate-limiting enzyme for hydrolysis of circulating triglyceride and
      is involved in HDL formation. We show that tissues containing LPL are major
      sources of CETP mRNA in several mammalian species, including some with low
      cholesteryl ester transfer activity in plasma. In hamsters, adipose tissue and
      heart were found to be the richest sources of both CETP and LPL mRNA; in situ
      hybridization studies showed that the same cell types (i.e. adipocytes or
      myocytes) contained CETP and LPL mRNA in these tissues. Isolated adipocytes
      synthesized active CETP. Dietary studies revealed a complex pattern of response
      of CETP mRNA levels in different tissues, which showed partial similarity to the
      changes in LPL mRNA abundance. However, high cholesterol diets resulted in
      increased CETP mRNA abundance in adipose tissue, heart, and skeletal muscle,
      without equivalent changes in LPL mRNA. Plasma HDL cholesteryl ester levels
      showed strong inverse correlations with CETP mRNA abundance in adipose tissue.
      The results suggest a conserved function of CETP in adipose tissue and heart,
      such as a co-ordinate action with LPL to enhance HDL turnover. Although there is
      considerable overlap in the tissue- and cell-specific pattern of CETP and LPL
      gene expression, dietary studies revealed only limited parallelism in response at
      the mRNA level. The increase in CETP mRNA in peripheral tissues in response to
      increased dietary cholesterol suggests that local induction of CETP synthesis may
      help to recycle cholesterol deposited in these tissues during lipolysis of
      dietary lipoproteins.

PMID- 1999441
TI  - Childhood conditions and adult height.
AB  - Self-reported height and childhood conditions among 1711 Danish male general
      workers born between 1923 and 1940 were analysed. No significant associations
      were found between adult height and father's occupation, growing up with both
      parents, paternal unemployment, sickness among the parents, parents receiving
      disability pension, economical problems in childhood, area of residence in
      childhood, and years at school. The study therefore provides no support for the
      hypothesis that poor childhood conditions are the cause of low adult height in
      this socially very homogeneous sample.

PMID- 1999439
TI  - Altered hapten recognition by two anti-digoxin hybridoma variants due to variable
      region point mutations.
AB  - Two spontaneous variants of the murine anti-digoxin antibody-producing hybridoma
      cell line 26-10 were isolated by two-color fluorescence-activated cell sorting on
      the basis of altered hapten binding. The variable region sequences of the
      antibodies produced by the mutant lines revealed that each contains a single
      amino acid change in the heavy chain second complementarity determining region. A
      Tyr to His change at position 50 leads to a 40-fold reduction in affinity for
      digoxin. A Ser to Phe mutation at position 52 results in a 300-fold reduction in
      affinity for digoxin. A competition assay involving 33 digoxin analogues was used
      to examine the specificity of hapten binding of 26-10 and the two mutant
      antibodies. The position 50 mutant has a distinct specificity change; it exhibits
      a preference for digoxin congeners containing a hydroxyl group at the steroid 12
      position, whereas the 26-10 parent does not. The affinities of all three
      antibodies for hapten are progressively lowered by substitutions of increasing
      size at the digoxin steroid D ring 16 position. Although 26-10 binds digoxin and
      its genin form equally, 12 and 16 steroid position substitutions which lower
      affinity also confer a preference for a sugar at the steroid 3 position. These
      results suggest that position 50 contributes to specificity of the antibody and
      that alterations of the hapten can lead to differences in recognition, possibly
      through a shift in hapten orientation within the binding site.

PMID- 1999440
TI  - Hyoscyamine 6 beta-hydroxylase, an enzyme involved in tropane alkaloid
      biosynthesis, is localized at the pericycle of the root.
AB  - Hyoscyamine 6 beta-hydroxylase (H6H; EC 1.14.11.11) catalyzes the first reaction
      in the biosynthetic pathway from hyoscyamine to scopolamine in several
      solanaceous plants. Four monoclonal antibodies were raised against H6H purified
      from cultured roots of Hyoscyamus niger. The IgG1 antibody mAb5 inhibited H6H
      activities present in cell-free extracts of H. niger roots and specifically
      recognized 38-40-kDa proteins from six different scopolamine-producing plant
      species in Western blot analysis after sodium dodecyl sulfate (SDS)
      polyacrylamide gel electrophoresis. The other three monoclonal antibodies all
      recognized SDS-denatured H6H protein from Hyoscyamus species, but did not bind to
      native H6H. Western blot analysis of protein extracts from various tissues of H.
      niger using these antibodies showed that H6H is abundant in cultured roots,
      present in plant roots, but absent in leaf, stem, calyx, cultured cells, and
      cultured shoots. Immunohistochemical studies using monoclonal antibody and
      immunogold-silver enhancement detected H6H only in the pericycle cells of the
      young root in several scopolamine-producing plants. Mature roots that underwent
      secondary growth and lacked the pericycle did not react with the antibody. This
      pericycle-specific localization of scopolamine biosynthesis provides an
      anatomical explanation for the tissue-specific biosynthesis of tropane alkaloids
      and may be important for translocation of tropane alkaloids from the root to the
      aerial parts.

PMID- 1999442
TI  - Biosocial influences on stature: a review.

PMID- 1999443
TI  - An estimation of inbreeding from isonymy in the historical (1734-1810) population
      of the Quebrada de Humahuaca (Jujuy, Argentina).
AB  - The method of isonymy to estimate inbreeding is applied to the historical
      population of the Quebrada de Humahuaca (Province de Jujuy, Republic of
      Argentina). Data from the baptismal records of the Parochial Church of Humahuaca
      from 1734 to 1810 were grouped into two periods, 1734-72 and 1773-1810. The
      analysis was carried out twice: (a) using the surnames exactly as they were
      registered; (b) combining homonymous surnames which were pronounced or spelt in a
      similar way. The random and non-random components of inbreeding have been
      investigated through different methods. There were no significant differences
      between the results of the two analyses, nor between the expected and observed
      isonymy. The value of F lies somewhere between those for offspring of first
      cousins once removed and second cousins once removed. There is a tendency for F
      and its components to increase through time. It is concluded that the high
      altitude aboriginal population of Humahuaca Parish must have behaved as a
      panmictic unit.

PMID- 1999444
TI  - Anthropometric indicators of children's nutrition in two Nigerian communities.
AB  - On a sample of some 2000 children living in two ecologically different zones (the
      Wooded and Guinea savanna) in Kwara state, Nigeria, body measurements were taken,
      to serve as indicators of the state of nutrition. There was more undernutrition
      in the Guinea savanna than in the Wooded. More males than females were
      undernourished in the Guinea savanna but not in the Wooded. It is argued that the
      differences between districts stem from social and cultural variables.

PMID- 1999445
TI  - Size at birth and some sociodemographic factors in gypsies in Hungary.
AB  - In 10,108 babies born to gypsy parents, birth weight, birth length and
      gestational age are compared with a national reference sample, taking into
      account maternal education, age, and birth interval. The gypsy babies tend
      consistently to be smaller, and this difference is attributable to the
      circumstances in which the gypsies live as well as the poorer maternal education.
      There appears to be a vicious circle--poor hygiene and living conditions
      adversely affect birth size, which in turn puts the child at a disadvantage in
      terms of survival, health and development.

PMID- 1999446
TI  - Intervals between marriage and first birth in mothers and daughters.
AB  - Marriage-first birth intervals are examined in two historical populations, Quebec
      (1608-1765) and Haut-Jura (1689-1980), comparing intervals in mothers and
      daughters, and in sister-sister pairs. The results point to a weak relationship
      between intervals of mothers and daughters, though it does not attain
      significance. Shared environment does not seem to be responsible since there is
      no association between pairs of sisters from the same populations.

PMID- 1999447
TI  - An evaluation of a national breast-feeding promotion programme in Honduras.
AB  - A significant increase occurred in the initiation and duration of breast-feeding
      among Honduran women between 1981 and 1987. Changes in population characteristics
      (e.g. level of education of women) would be expected to lead to a decrease in
      breast-feeding at each infant age, but these were offset by behavioural changes
      that led to an increase in the likelihood of initiation and continuation of
      breast-feeding. An exploration of relevant factors suggests that the PROALMA
      breast-feeding promotion programme has had a profound effect on the breast
      feeding behaviour of Honduran mothers.

PMID- 1999448
TI  - The relationship between sociodemographic variables and pregnancy loss in a rural
      area of Bangladesh.
AB  - This study examines the relationship between eight sociodemographic variables and
      the risk of pregnancy loss in a rural area of Bangladesh. The risks of
      spontaneous miscarriage and stillbirth were significantly associated with
      maternal age, pregnancy order and previous pregnancy wastage.

PMID- 1999449
TI  - Social class as a risk factor for infant mortality in an Australian population.
AB  - Studies in other countries have identified social class as a risk factor for
      infant mortality. In Australia there is no systematic collection of population
      data by social class, partly due to the absence of a recognized measure. The use
      of occupational prestige as an indicator of social class is discussed and
      Australian prestige scales reviewed. In a population based study, logistic
      regression analysis of infant mortality in an Australian (NSW) population shows
      the effects of social class on infant mortality which remain when maternal age,
      marital status and parity are controlled.

PMID- 1999450
TI  - A reversal of fertility trends in Singapore.
AB  - Free access to contraception and effective legislation measures, have resulted in
      a decline in fertility in Singapore. A new population policy of 'three children
      or more if you can afford it' was therefore introduced in 1986. This paper
      discusses the new population policies and measures their effect on fertility in
      Singapore.

PMID- 1999451
TI  - Changes in contraceptive use and fertility: El Salvador, 1978-88.
AB  - In El Salvador from 1978 to 1988, contraceptive use among married women 15-44
      years of age increased from 34% to 47%, and the total fertility rate declined
      from 6.3 to 4.6 children per woman. Most of this change took place from 1978 to
      1985. Sterilization is the most prevalent method used, but nearly one-half of the
      women who are sterilized did not use any contraception before their operation.
      Few young couples use reversible methods of contraception to space births or
      delay the start of childbearing. On average, women wait 8 years after marriage
      and have nearly three children before they use contraception.

PMID- 1999452
TI  - Maternal and infant demographics and health status: a comparison of black,
      Caucasian, and Hispanic families.
AB  - The relationships among ethnicity, demographics, smoking and drinking habits, and
      maternal and infant health were examined in a sample of 171 low-income and low
      risk Black, Caucasian, and Hispanic families. Few ethnic differences in the
      health status of the mothers and their infants emerged when ethnic differences
      were directly examined; however, a latent variable analysis indicated that
      ethnicity was related to smoking and drinking habits such that Caucasian mothers
      were more likely to smoke and drink. Smoking and drinking, in turn, led to
      smaller infant size at birth. Demographic differences found in level of income,
      education, and family composition suggest that low-income families are not
      necessarily homogeneous.

PMID- 1999453
TI  - Assembly of Torpedo acetylcholine receptors in Xenopus oocytes.
AB  - To study pathways by which acetylcholine receptor (AChR) subunits might assemble,
      Torpedo alpha subunits were expressed in Xenopus oocytes alone or in combination
      with beta, gamma, or delta subunits. The maturation of the conformation of the
      main immunogenic region (MIR) on alpha subunits was measured by binding of mAbs
      and the maturation of the conformation of the AChR binding site on alpha subunits
      was measured by binding of alpha-bungarotoxin (alpha Bgt) and cholinergic
      ligands. The size of subunits and subunit complexes was assayed by sedimentation
      on sucrose gradients. It is generally accepted that native AChRs have the subunit
      composition alpha 2 beta gamma delta. Torpedo alpha subunits expressed alone
      resulted in an amorphous range of complexes with little affinity for alpha Bgt or
      mAbs to the MIR, rather than in a unique 5S monomeric assembly intermediate
      species. A previously recognized temperature-dependent failure in alpha subunit
      maturation may cause instability of the monomeric assembly intermediate and
      accumulation of aggregated denatured alpha subunits. Coexpression of alpha with
      beta subunits also resulted in an amorphous range of complexes. However,
      coexpression of alpha subunits with gamma or delta subunits resulted in the
      efficient formation of 6.5S alpha gamma or alpha delta complexes with high
      affinity for mAbs to the MIR, alpha Bgt, and small cholinergic ligands. These
      alpha gamma and alpha delta subunit pairs may represent normal assembly
      intermediates in which Torpedo alpha is stabilized and matured in conformation.
      Coexpression of alpha, gamma, and delta efficiently formed 8.8S complexes,
      whereas complexes containing alpha beta and gamma or alpha beta and delta
      subunits are formed less efficiently. Assembly of beta subunits with complexes
      containing alpha gamma and delta subunits may normally be a rate-limiting step in
      assembly of AChRs.

PMID- 1999455
TI  - Topologically restricted appearance in the developing chick retinotectal system
      of Bravo, a neural surface protein: experimental modulation by environmental
      cues.

PMID- 1999454
TI  - The properdin-like type I repeats of human thrombospondin contain a cell
      attachment site.
AB  - Thrombospondin (TS) is a modular adhesive glycoprotein that contains three
      domains previously implicated in the attachment of cells to TS. These include the
      amino-terminal heparin-binding domain, the carboxy terminal cell or platelet
      binding domain, and an RGDA sequence of TS. We have characterized a mAb against
      human TS, designated A4.1, which inhibits the attachment of human melanoma cells
      (G361) to TS. The epitope for A4.1 lies within the amino terminal half of the
      central stalklike region of TS which is distinct from the three known cell
      attachment sites. This region of TS is recovered in a 50-kD peptide after
      chymotryptic digestion of TS in EDTA. It contains the procollagen-like domain of
      TS as well as three type I repeats of a 60-residue segment homologous to two
      malarial proteins and the complement proteins properdin, and factors C6 through
      C9. The purified chymotryptic fragment is an effective attachment factor for G361
      cells. A4.1 blocks adhesion to the 50-kD domain, as do some sulfated
      glycoconjugates. RGD (and RGE) peptides and mAbs against other domains of TS are
      not inhibitory. Peptides (19 mers) based on the core homology sequence of the
      three type I repeats of TS are potent attachment factors for these cells, and
      this adhesion is also inhibited by sulfated glycoconjugates. A polyclonal
      antibody raised against one of these peptides inhibits adhesion of G361 cells to
      the peptides, to the 50-kD fragment and to intact TS. Thus a new cell-adhesion
      site has been identified in TS whose sequence is very similar to the site
      identified in region II of the circumsporozoite protein of malaria parasites
      (Rich, K. A., F. W. George IV, J. L. Law, and W. J. Martin. 1990. Science (Wash.
      DC) 249:1574-1577. Thus there may be a common receptor which binds TS, malarial
      proteins, and properdin.

PMID- 1999456
TI  - Differentiation requires continuous regulation.

PMID- 1999457
TI  - Identification of a novel nuclear domain.
AB  - For most known nuclear domains (ND), specific functions have been identified. In
      this report we used murine mAbs and human autoantibodies to investigate precisely
      circumscribed structures 0.2-0.3 micron in diameter which appear as "nuclear
      dots" distributed throughout the nucleoplasm. Nuclear dots are metabolically
      stable and resistant to nuclease digestion and salt extraction. The localization
      of nuclear dots is separate from kinetochores, centromeres, sites of mRNA
      processing and tRNA synthesis, nuclear bodies, and chromosomes. The nuclear dots,
      therefore, represent a novel ND. Nuclear dots break down as cells enter metaphase
      and reassemble at telophase. In interphase cells, nuclear dots are frequently
      "paired," and some are visible as "doublets" when stained with one particular
      antiserum. The number of dot doublets increased when quiescent cells were
      stimulated with serum although the total number of dots did not change
      substantially. One of the antigens was identified as a protein with a molecular
      mass of approximately 55 kD showing three charge isomers in the pI range of 7.4
      to 7.7. Autoantibodies affinity purified from this nuclear dot protein (NDP-55)
      show nuclear dots exclusively. Nuclear dot-negative rat liver parenchymal cells
      became positive after chemical hepatectomy, suggesting involvement of the NDP-55
      in the proliferative state of cells.

PMID- 1999458
TI  - p34cdc2 acts as a lamin kinase in fission yeast.
AB  - The nuclear lamina is an intermediate filament network that underlies the nuclear
      membrane in higher eukaryotic cells. During mitosis in higher eukaryotes, nuclear
      lamins are phosphorylated by a mitosis-specific kinase and this induces
      disassembly of the lamina structure. Recently, p34cdc2 protein kinase purified
      from starfish has been shown to induce phosphorylation of lamin proteins and
      disassembly of the nuclear lamina when incubated with isolated chick nuclei
      suggesting that p34cdc2 is likely to be the mitotic lamin kinase (Peter, M., J.
      Nakagawa, M. Doree, J.C. Labbe, and E.A. Nigg. 1990b. Cell. 45:145-153). To
      confirm and extend these studies using genetic techniques, we have investigated
      the role of p34cdc2 in lamin phosphorylation in the fission yeast. As fission
      yeast lamins have not been identified, we have introduced a cDNA encoding the
      chicken lamin B2 protein into fission yeast. We report here that the chicken
      lamin B2 protein expressed in fission yeast is assembled into a structure that
      associates with the nucleus during interphase and becomes dispersed throughout
      the cytoplasm when cells enter mitosis. Mitotic reorganization correlates with
      phosphorylation of the chicken lamin B2 protein by a mitosis-specific yeast lamin
      kinase with similarities to the mitotic lamin kinase of higher eukaryotes. We
      show that a lamin kinase activity can be detected in cell-free yeast extracts and
      in p34cdc2 immunoprecipitates prepared from yeast cells arrested in mitosis. The
      fission yeast lamin kinase activity is temperature sensitive in extracts and
      immunoprecipitates prepared from strains bearing temperature-sensitive mutations
      in the cdc2 gene. These results in conjunction with the previously reported
      biochemical studies strongly suggest that disassembly of the nuclear lamina at
      mitosis in higher eukaryotic cells is a consequence of direct phosphorylation of
      nuclear lamins by p34cdc2.

PMID- 1999459
TI  - A nascent membrane protein is located adjacent to ER membrane proteins throughout
      its integration and translation.
AB  - The immediate environment of nascent membrane proteins undergoing integration
      into the ER membrane was investigated by photocrosslinking. Nascent polypeptides
      of different lengths, each containing a single IgM transmembrane sequence that
      functions either as a stop-transfer or a signal-anchor sequence, were synthesized
      by in vitro translation of truncated mRNAs in the presence of N epsilon-(5-azido
      2-nitrobenzoyl)-Lys-tRNA, signal recognition particle, and microsomal membranes.
      This yielded nascent chains with photoreactive probes at one end of the
      transmembrane sequence where two lysine residues are located. When irradiated,
      these nascent chains reacted covalently with several ER proteins. One prominent
      crosslinking target was a glycoprotein similar in size to a protein termed mp39,
      shown previously to be situated adjacent to a secretory protein during its
      translocation across the ER membrane (Krieg, U. C., A. E. Johnson, and P. Walter.
      1989. J. Cell Biol. 109:2033-2043; Wiedmann, M., D. Goerlich, E. Hartmann, T. V.
      Kurzchalia, and T. A. Rapoport. 1989. FEBS (Fed. Eur. Biochem. Soc.) Lett.
      257:263-268) and likely to be identical to a protein previously designated the
      signal sequence receptor (Wiedmann, M., T. V. Kurzchalia, E. Hartmann, and T. A.
      Rapoport. 1987. Nature (Lond.). 328:830-833). Changing the orientation of the
      transmembrane domain in the bilayer, or making the transmembrane domain the first
      topogenic sequence in the nascent chain instead of the second, did not
      significantly alter the identities of the ER proteins that were the primary
      crosslinking targets. Furthermore, the nascent chains crosslinked to the mp39
      like glycoprotein and other microsomal proteins even after the cytoplasmic tail
      of the nascent chain had been lengthened by nearly 100 amino acids beyond the
      stop-transfer sequence. Yet when the nascent chain was allowed to terminate
      normally, the major photocrosslinks were no longer observed, including in
      particular that to the mp39-like glycoprotein. These results show that the
      transmembrane segment of a nascent membrane protein is located adjacent to the
      mp39-like glycoprotein and other ER proteins during the integration process, and
      that at least a portion of the nascent chain remains in close proximity to these
      ER proteins until translation has been completed.

PMID- 1999460
TI  - Identification of a novel, N-ethylmaleimide-sensitive cytosolic factor required
      for vesicular transport from endosomes to the trans-Golgi network in vitro.
AB  - We have recently described a cell-free system that reconstitutes the vesicular
      transport of 300-kD mannose 6-phosphate receptors from late endosomes to the
      trans-Golgi network (TGN). We report here that the endosome----TGN transport
      reaction was significantly inhibited by low concentrations of the alkylating
      agent, N-ethylmaleimide (NEM). Addition of fresh cytosol to NEM-inactivated
      reaction mixtures restored transport to at least 80% of control levels.
      Restorative activity was only present in cytosol fractions, and was sensitive to
      trypsin treatment or incubation at 100 degrees C. A variety of criteria
      demonstrated that the restorative activity was distinct from NSF, an NEM
      sensitive protein that facilitates the transport of proteins from the ER to the
      Golgi complex and between Golgi cisternae. Cytosol fractions immunodepleted of
      greater than or equal to 90% of NSF protein, or heated to 37 degrees C to
      inactivate greater than or equal to 93% of NSF activity, were fully able to
      restore transport to NEM-treated reaction mixtures. The majority of restorative
      activity sedimented as a uniform species of 50-100 kD upon glycerol gradient
      centrifugation. We have termed this activity ETF-1, for endosome----TGN transport
      factor-1. Kinetic experiments showed that ETF-1 acts at a very early stage in
      vesicular transport, which may reflect a role for this factor in the formation of
      nascent transport vesicles. GTP hydrolysis appears to be required throughout the
      transport reaction. The ability of GTP gamma S to inhibit endosome----TGN
      transport required the presence of donor, endosome membranes, and cytosol, which
      may reflect a role for guanine nucleotides in vesicle budding. Finally, ETF-1
      appears to act before a step that is blocked by GTP gamma S, during the process
      by which proteins are transported from endosomes to the TGN in vitro.

PMID- 1999461
TI  - Multilayering and loss of apical polarity in MDCK cells transformed with viral K
      ras.
AB  - The effects of viral Kirsten ras oncogene expression on the polarized phenotype
      of MDCK cells were investigated. Stable transformed MDCK cell lines expressing
      the v-K-ras oncogene were generated via infection with a helper-independent
      retroviral vector construct. When grown on plastic substrata, transformed cells
      formed continuous monolayers with epithelial-like morphology. However, on
      permeable filter supports where normal cells form highly polarized monolayers,
      transformed MDCK cells detached from the substratum and developed multilayers.
      Morphological analysis of the multilayers revealed that oncogene expression
      perturbed the polarized organization of MDCK cells such that the transformed
      cells lacked an apical--basal axis around which the cytoplasm is normally
      organized. Evidence for selective disruption of apical membrane polarity was
      provided by immunolocalization of membrane proteins; a normally apical 114-kD
      protein was randomly distributed on the cell surface in the transformed cell
      line, whereas normally basolateral proteins remained exclusively localized to
      areas of cell contact and did not appear on the free cell surface. The discrete
      distribution of the tight junction-associated ZO-1 protein as well as
      transepithelial resistance and flux measurements suggested that tight junctions
      were also assembled. These findings indicate that v-K-ras transformation alters
      cell-substratum and cell-cell interactions in MDCK cells. Furthermore, v-K-ras
      expression perturbs apical polarization but does not interfere with the
      development of a basolateral domain, suggesting that apical and basolateral
      polarity in epithelial cells may be regulated independently.

PMID- 1999462
TI  - Chicken nonmuscle myosin heavy chains: differential expression of two mRNAs and
      evidence for two different polypeptides.
AB  - Two different mRNAs encoding two different nonmuscle myosin heavy chains (MHCs)
      of approximately 200 kD have been identified in chicken nonmuscle cells, in
      agreement with the results of Katsuragawa et al. (Katsuragawa, Y., M. Yanagisawa,
      A. Inoue, and T. Masaki. 1989. Eur. J. Biochem. 184:611-616). In this paper, we
      quantitate the content of mRNA encoding the two MHCs in a number of different
      tissues using RNA blot analysis with two specific oligonucleotide probes. Our
      results show that the relative content of mRNA encoding MHC-A and MHC-B differs
      in a tissue-dependent manner. Thus the ratio of mRNA encoding MHC-A versus MHC-B
      varies from greater than 9:1 in spleen and intestinal epithelial cells, to 6:4 in
      kidney and 2:8 in brain. The effect of serum on MHC mRNA expression was studied
      in serum-starved cultures of chick embryo fibroblasts. Serum stimulation results
      in a threefold increase in the mRNA encoding MHC-A and a threefold decrease in
      mRNA encoding MHC-B. Using SDS polyacrylamide gels, we have separated two
      nonmuscle MHC isoforms (198 and 196 kD) that can be distinguished from each other
      by two-dimensional peptide mapping of chymotryptic digests. We provide
      preliminary evidence that the MHC-A mRNA encodes the 196-kD polypeptide and that
      the MHC-B mRNA encodes the 198-kD polypeptide.

PMID- 1999465
TI  - A photoreceptor calcium binding protein is recognized by autoantibodies obtained
      from patients with cancer-associated retinopathy.
AB  - Cancer-associated retinopathy (CAR), a paraneoplastic syndrome, is characterized
      by the degeneration of retinal photoreceptors under conditions where the tumor
      and its metastases have not invaded the eye. The retinopathy often is apparent
      before the diagnosis of cancer and may be associated with autoantibodies that
      react with specific sites in the retina. We have examined the sera from patients
      with CAR to further characterize the retinal antigen. Western blot analysis of
      human retinal proteins reveals a prominent band at 26 kD that is labeled by the
      CAR antisera. Antibodies to the 26-kD protein were affinity-purified from complex
      CAR antisera and used for EM-immunocytochemical localization of the protein to
      the nuclei, inner and outer segments of both rod and cone cells. Other antibodies
      obtained from the CAR sera did not label photoreceptors. Using the affinity
      purified antibodies for detection, the 26-kD protein, designated p26, was
      purified to homogeneity from the outer segments of bovine rod photoreceptor cells
      by Phenyl-Sepharose and ion exchange chromatography. Partial amino acid sequence
      of p26 was determined by gas phase Edman degradation and revealed extensive
      homology with a cone-specific protein, visinin. Based upon structural
      relatedness, both the p26 rod protein and visinin are members of the calmodulin
      family and contain calcium binding domains of the E-F hand structure.

PMID- 1999464
TI  - Poleward microtubule flux mitotic spindles assembled in vitro.
AB  - In the preceding paper we described pathways of mitotic spindle assembly in cell
      free extracts prepared from eggs of Xenopus laevis. Here we demonstrate the
      poleward flux of microtubules in spindles assembled in vitro, using a
      photoactivatable fluorescein covalently coupled to tubulin and multi-channel
      fluorescence videomicroscopy. After local photoactivation of fluorescence by UV
      microbeam, we observed poleward movement of fluorescein-marked microtubules at a
      rate of 3 microns/min, similar to rates of chromosome movement and spindle
      elongation during prometaphase and anaphase. This movement could be blocked by
      the addition of millimolar AMP-PNP but was not affected by concentrations of
      vanadate up to 150 microM, suggesting that poleward flux may be driven by a
      microtubule motor similar to kinesin. In contrast to previous results obtained in
      vivo (Mitchison, T. J. 1989. J. Cell Biol. 109:637-652), poleward flux in vitro
      appears to occur independently of kinetochores or kinetochore microtubules, and
      therefore may be a general property of relatively stable microtubules within the
      spindle. We find that microtubules moving towards poles are dynamic structures,
      and we have estimated the average half-life of fluxing microtubules in vitro to
      be between approximately 75 and 100 s. We discuss these results with regard to
      the function of poleward flux in spindle movements in anaphase and prometaphase.

PMID- 1999463
TI  - Mitotic spindle assembly by two different pathways in vitro.
AB  - We have used Xenopus egg extracts to study spindle morphogenesis in a cell-free
      system and have identified two pathways of spindle assembly in vitro using
      methods of fluorescent analogue cytochemistry. When demembranated sperm nuclei
      are added to egg extracts arrested in a mitotic state, individual nuclei direct
      the assembly of polarized microtubule arrays, which we term half-spindles; half
      spindles then fuse pairwise to form bipolar spindles. In contrast, when sperm
      nuclei are added to extracts that are induced to enter interphase and arrested in
      the following mitosis, a single sperm nucleus can direct the assembly of a
      complete spindle. We find that microtubule arrays in vitro are strongly biased
      towards chromatin, but this does not depend on specific kinetochore-microtubule
      interactions. Indeed, although we have identified morphological and probably
      functional kinetochores in spindles assembled in vitro, kinetochores appear not
      to play an obligate role in the establishment of stable, bipolar microtubule
      arrays in either assembly pathway. Features of the two pathways suggest that
      spindle assembly involves a hierarchy of selective microtubule stabilization,
      involving both chromatin-microtubule interactions and antiparallel microtubule
      microtubule interactions, and that fundamental molecular interactions are
      probably the same in both pathways. This in vitro reconstitution system should be
      useful for identifying the molecules regulating the generation of asymmetric
      microtubule arrays and for understanding spindle morphogenesis in general.

PMID- 1999466
TI  - Identification of novel centromere/kinetochore-associated proteins using
      monoclonal antibodies generated against human mitotic chromosome scaffolds.
AB  - We describe the generation of 11 monoclonal antibodies that bind to the
      centromere/kinetochore region of human mitotic chromosomes. These antibodies were
      raised against mitotic chromosome scaffolds and screened for
      centromere/kinetochore binding by indirect immunofluorescence against purified
      chromosomes. Immunoblot analyses with these antibodies revealed that all of the
      antigens are greater than 200 kD and are components of nuclei, chromosomes,
      and/or chromosome scaffolds. Comparison of the immunolocalization of the antigens
      with that observed for the centromere-associated protein CENP-B revealed that
      each of these centromere/kinetochore proteins lies more peripherally to the DNA
      than does CENP-B. In cells normally progressing through the cell cycle, these
      antigens displayed four distinct patterns of centromere/kinetochore association,
      corresponding to a minimum of four novel centromere/kinetochore-associated
      proteins.

PMID- 1999467
TI  - Participation of a novel 88-kD protein in the biogenesis of murine class I
      histocompatibility molecules.
AB  - Chemical cross-linking and gel permeation chromatography were used to examine
      early events in the biogenesis of class I histocompatibility molecules. We show
      that newly synthesized class I heavy chains associate rapidly and quantitatively
      with an 88-kD protein in three murine tumor cell lines. This protein (p88) does
      not appear to possess Asn-linked glycans and it is not the abundant ER protein,
      GRP94. The class I-p88 complex exists transiently (t1/2 = 20-45 min depending on
      the specific class I heavy chain) and several lines of evidence suggest that p88
      dissociates from the complex while still in the ER. Dissociation is not triggered
      upon binding of beta 2-microglobulin to the heavy chain (t1/2 = 2-5 min).
      However, the rate of dissociation does correlate with the characteristic rate of
      ER to Golgi transport for the particular class I molecule studied. Consequently,
      dissociation of p88 may be rate limiting for ER to Golgi transport. Class I
      molecules bind antigenic peptides, apparently in the ER, for subsequent
      presentation to cytotoxic T lymphocytes at the cell surface. p88 could promote
      peptide binding or it may retain class I molecules in the ER during formation of
      the ternary complex of heavy chain, beta 2-microglobulin, and peptide.

PMID- 1999468
TI  - Microtubule depolymerization promotes particle and chromosome movement in vitro.
AB  - We have developed a system for studying the motions of cellular objects attached
      to depolymerizing microtubules in vitro. Radial arrays of microtubules were grown
      from lysed and extracted Tetrahymena cells attached to a glass coverslip that
      formed the top of a light microscope perfusion chamber. A preparation of
      chromosomes, which also contained vesicles, was then perfused into the chamber
      and allowed to bind to the microtubule array. The concentration of tubulin was
      then reduced by perfusing buffer that lacked both tubulin and nucleotide
      triphosphates, and the resulting microtubule depolymerization was observed by
      light microscopy. A fraction of the bound objects detached in the flow and washed
      away, while others stabilized the microtubules to which they were bound. Some of
      the particles and chromosomes, however, moved in toward the Tetrahymena ghost as
      their associated microtubules shortened. The mean speeds for particles and
      chromosomes were 26 +/- 20 and 15 +/- 12 microns/min, respectively. These motions
      occurred when nucleotide triphosphate levels were very low, as a result of either
      dilution or by the action of apyrase. Furthermore, the motions were unaffected by
      100 microM sodium orthovanadate, suggesting that these forces are not the result
      of ATP hydrolysis by a minus end-directed mechanoenzyme. We conclude that
      microtubule depolymerization provided the free energy for the motions observed.
      All the objects that we studied in detail moved against a stream of buffer
      flowing at approximately 100 microns/s, so that the force being developed was at
      least 10(-7) dynes. This force is large enough to contribute to some forms of
      motility in living cells.

PMID- 1999469
TI  - Suppression by antisense mRNA demonstrates a requirement for the glial fibrillary
      acidic protein in the formation of stable astrocytic processes in response to
      neurons.
AB  - The glial fibrillary acidic protein (GFAP) is a glial-specific intermediate
      filament protein, which is expressed in astrocytes in the central nervous system,
      as well as in astrocytoma cell lines. To investigate the function of GFAP, we
      have studied the human astrocytoma cell line, U251, which constitutively
      expresses GFAP and vimentin in the same 10-nm filaments. These cells respond to
      neurons in vitro in the same way as primary astrocytes: they withdraw from the
      cell cycle, support neuronal cell survival and neurite outgrowth, and they extend
      complex, GFAP-positive processes. To determine the role of GFAP in these
      responses, we have specifically suppressed its expression by stably transfecting
      the U251 cells with an antisense GFAP construct. Two stable antisense cell lines
      from separate transfections were isolated and were shown to be GFAP negative by
      Northern and Western blot analyses, and by immunofluorescence studies. The
      antisense cell lines were inhibited in their ability to extend significant glial
      processes in response to neurons. In culture with primary neurons, the average
      increase in process length of the U251 cells was nearly 400%, as compared to only
      14% for the antisense transfectants. The other neuron induced responses of
      astrocytes, i.e., proliferative arrest and neuronal support, were not affected in
      these cell lines. These data support the conclusion that the glial-specific
      intermediate filament protein, GFAP, is required for the formation of stable
      astrocytic processes in response to neurons.

PMID- 1999472
TI  - Serum factor revealing two distant phases of negative proliferation control in
      mitogen-stimulated normal fibroblasts.
AB  - When quiescent normal skin fibroblasts are stimulated by mitogens such as
      epidermal growth factor (EGF), the proportion of cells entering a division cycle
      decreases with increasing cell density. The presence of a synthetic double
      stranded RNA (poly I:C) enhances this density-related restriction. Fetal calf
      serum (FCS) as well as human serum (HS) and human platelet-poor plasma (HPPP)
      completely abrogate the inhibiting effect of cell density on EGF mitogenicity,
      both in the presence and absence of poly I:C. HS and HPPP are up to ten times
      more potent than FCS in overcoming density-related restriction of EGF
      mitogenicity in human skin fibroblasts, whereas the mitogenic potencies of FCS,
      HS and HPPP in the absence of EGF are identical. Thus the mitogenic activity of
      FCS, HS and HPPP and their ability to overcome the density-related restriction of
      EGF-induced proliferation may be due to different molecules. Addition of FCS or
      HS at various times after EGF exposure reveals two distinct control points within
      the prereplicative phase: one within the first 2 hours and the other between 10
      and 20 hours after the beginning of EGF exposure. Thus, the interactions of EGF,
      serum, and poly I:C reveal the kinetics of a cell density-related mechanism of
      negative proliferation control.

PMID- 1999470
TI  - Regulated plasmalemmal expansion in nerve growth cones.
AB  - To study the mechanisms underlying plasmalemmal expansion in the nerve growth
      cone, a cell-free assay was developed to quantify membrane addition, using ligand
      binding and sealed growth cone particles isolated by subcellular fractionation
      from fetal rat brain. Exposed versus total binding sites of 125I-wheat germ
      agglutinin were measured in the absence or presence of saponin, respectively,
      after incubation with various agents. Ca2(+)-ionophore A23187 in the presence of
      Ca2+ increases the number of binding sites (Bmax) but does not change their
      affinity (KD), indicating that new receptors appear on the plasma membrane.
      Similarly, membrane depolarization by high K+ or veratridine significantly
      induces, in a Ca2(+)-dependent manner, the externalization of lectin binding
      sites from an internal pool. Morphometric analysis of isolated growth cones
      indicates that A23187 and high K+ treatment cause a significant reduction in a
      specific cytoplasmic membrane compartment, thus confirming the lectin labeling
      results and identifying the plasmalemmal precursor. The isolated growth cones
      take up gamma-amino-butyric acid and serotonin, but show no evidence for Ca2(+)
      dependent transmitter release so that transmitter exocytosis is dissociated from
      plasmalemmal expansion. The data demonstrate that plasmalemmal expansion in the
      growth cone is a regulated process and identify an internal pool of precursor
      membrane.

PMID- 1999471
TI  - Expression of P30, a protein with adhesive properties, in Schwann cells and
      neurons of the developing and regenerating peripheral nerve.
AB  - P30 is a heparin-binding protein with adhesive and neurite outgrowth-promoting
      properties present at high levels in the developing rat central nervous system
      (Rauvala, H., and R. Pihlaskari. 1987 J. Biol. Chem. 262:16625-16635). Partial
      sequencing of p30 has revealed homology or identity with HMG-1 (Rauvala, H., J.
      Merenmies, R. Pihlaskari, M. Korkolainen, M.-L. Huhtala, and P. Panula. 1988. J.
      Cell Biol. 107:2292-2305), a 28-kD protein that was originally purified from the
      thymus (Goodwin, G.H., C. Sanders, and E. W. Johns. 1973. Eur. J. Biochem. 38:14
      19) which binds DNA in vitro. We have analyzed the distribution of p30 in the
      developing rat peripheral nervous system (PNS). P30 was detected by
      immunohistochemistry and Western blot analysis using antibodies raised against
      intact p30 and against a synthetic peptide corresponding to the amino terminus of
      the p30 molecule. P30 was localized to nonnuclear compartments of neurons and
      peripheral glial cells (Schwann cells). P30 immunoreactivity of PNS neurons
      persisted into adulthood. In contrast, Schwann cell staining decreased after the
      second postnatal week and was not detectable in adult animals. Neuron-Schwann
      cell contact was correlated with diminished p30 levels in Schwann cells. Schwann
      cells of the normal adult sciatic nerve did not express p30; however, when
      deprived of axonal contact by nerve transection, the Schwann cells of the distal
      nerve stained intensely for p30. In addition, when Schwann cells and dorsal root
      ganglion neurons were grown in coculture, Schwann cells that were associated with
      neurites were not as intensely stained by anti-p30 as Schwann cells that were not
      in contact with neurons. The pattern of p30 expression during development and
      regeneration, and its apparent regulation by cell-cell contact suggests that p30
      plays a role in the interaction between neurons and Schwann cells during
      morphogenesis of peripheral nerves.

PMID- 1999473
TI  - Control of the intracellular Ca(2+)-concentration and the inositol phosphate
      accumulation in dog thyrocyte primary culture: evidence for different kinetics of
      Ca(2+)-phosphatidylinositol cascade activation and for involvement in the
      regulation of H2O2 production.
AB  - Carbachol, through a muscarinic receptor, thyrotropin-releasing hormone (TRH),
      prostaglandin F2 alpha (PGF2 alpha), bradykinin, and adenosine triphosphate (ATP)
      increased the apparent [Ca2+]i (intracellular free Ca2(+)-concentration) of dog
      thyrocytes in primary culture. The [Ca2+]i measured by the Quin-2 technique rose
      immediately after the addition of the agonists and reached a maximal value after
      less than 30 seconds. Afterwards, the [Ca2+]i declined to a plateau higher than
      the basal level when the cells were triggered with carbachol. By contrast, in
      most experiments with PGF2 alpha and in the case of bradykinin, TRH, and ATP, the
      [Ca2+]i returned to the basal value. If the extracellular Ca2+ was chelated by
      excess of EGTA, the addition of all agents caused a sharp reduced transient rise
      in the [Ca2+]i followed by a decline of the [Ca2+]i often below the basal level
      (especially in the case of carbachol). It is suggested that the first transient
      phase of these responses is due at least in part to the mobilisation of Ca2+ from
      intracellular stores whereas the second sustained phase of the response to
      carbachol mainly originates from an increased Ca2+ influx into the thyrocytes.
      Carbachol, bradykinin, TRH, PGF2 alpha, and ATP also increased generation of
      inositol phosphates in dog thyrocytes. This effect was sustained when the cells
      were triggered with carbachol and was more transient with bradykinin, TRH, PGF2
      alpha, or ATP. All these agents and the phorbdester TPA as well as forskolin
      enhanced to various extent the thyrocyte H2O2 generation. This enhancement was
      severely reduced in the absence of extracellular Ca2+ and was mimicked by Ca2+
      ionophores in the presence of extracellular Ca2+ especially in synergy with
      protein kinase C activators. These data suggest that the dog thyrocyte H2O2
      generation, the limiting step of the thyroid hormone synthesis, is modulated by
      carbachol, TRH, PGF2 alpha, bradykinin, and ATP through their action on the
      Ca2(+)-phosphatidylinositol cascade.

PMID- 1999474
TI  - Studies on the spermatogenic sulfogalactolipid binding protein SLIP 1.
AB  - We have purified the testicular sulfogalactolipid binding protein SLIP 1 and
      shown by photoaffinity labeling that it contains an ATP binding site. Purified
      SLIP 1 was fluorescently labeled and shown to retain specific sulfogalactolipid
      binding function. This probe was used to investigate the topology of SLIP 1
      binding sites on testicular germ cells. The binding pattern precisely coincided
      with the previously demonstrated asymmetric surface domains of
      sulfogalactoglycerolipid (SGG). Occasionally these SGG-containing, SLIP 1-binding
      cell surface domains exactly coincided with structural features on the cell
      surface as detected by differential interference contrast microscopy. These
      results demonstrate that SLIP 1/SGG interactions could provide an effective
      intercellular communication network between testicular germ cells within the
      seminiferous tubule.

PMID- 1999475
TI  - Developmental patterns in the antioxidant defenses of the housefly, Musca
      domestica.
AB  - The activities of superoxide dismutase (SOD), catalase, glutathione peroxidase,
      glutathione S-transferases, GSSG reductase, thiol transferases, gamma
      glutamylcysteine synthetase, and glucose-6-phosphate dehydrogenase, and the
      concentrations of H2O2 and reduced and oxidized glutathione were determined in
      the various developmental stages of houseflies. Housefly development was
      correlated with a progressive increase of cellular oxidizing equivalents and a
      loss of cellular reducing capacity. The loss of reducing equivalents appeared to
      result from a decrease in the activity of enzymes involved in glutathione and
      NADPH synthesis and a concomitant increase in glutathione-oxidizing enzymes.
      Relatively little change was observed in SOD activity during housefly
      development; however, the electrophoretic pattern of MnSOD varied in a manner
      specific to developmental stage. A striking increase in H2O2 concentration
      occurred prior to pupation possibly due to changes in substrate catabolism. These
      results support the hypothesis that the cellular environment becomes
      progressively more oxidizing during development.

PMID- 1999476
TI  - Growth factor-independent proliferation of normal human neonatal keratinocytes:
      production of autocrine- and paracrine-acting mitogenic factors.
AB  - When normal human foreskin keratinocytes were cultured in the absence of
      polypeptide growth factors at densities above 5 x 10(3)/cells cm2, the cells
      proliferated continuously and the addition of IGF-I, EGF, TGF alpha, bFGF, or
      aFGF did not significantly alter growth rate. Heparin sulfate, TGF beta, or
      suramin inhibited keratinocyte growth factor-independent proliferation. The
      addition of EGF, TGF alpha, or aFGF reversed heparin-induced growth inhibition,
      while bFGF partially negated this effect. RIA of keratinocyte-derived conditioned
      medium (CM) indicated the presence of TGF alpha peptide at a concentration of
      approximately 235 pg/ml. In contrast, clonal growth of keratinocytes required the
      addition of growth factors to the basal medium. Keratinocyte-derived CM replaced
      EGF in stimulating keratinocyte clonal growth, and an anti-EGF receptor mAb
      inhibited CM-induced keratinocyte clonal growth. In addition to its effect on
      keratinocytes, keratinocyte-derived CM stimulated the incorporation of
      [3H]thymidine by quiescent cultures of human foreskin fibroblasts, mouse AKR-2B
      cells, and EGF-receptorless mouse NR6 cells. CM-stimulated [3H]thymidine
      incorporation into quiescent normal human fibroblasts was partially reduced in
      the presence of anti-EGF receptor mAb. Heparin sulfate partially inhibited CM
      induced keratinocyte clonal growth and [3H]thymidine incorporation into quiescent
      AKR-2B cells. We hypothesize from these data that autocrine and paracrine-acting
      factors produced by keratinocytes mediated their effect through the activation of
      both EGF receptor-dependent and EGF receptor-independent mitogenic pathways and
      that some of these factors appear to be sensitive to inhibition by heparin.

PMID- 1999477
TI  - WS-1 human fibroblasts contain distinct calcium and protein kinase C-mediated
      pathways for activation of Na+/H+ exchange: contrasting effects of thrombin and
      PMA.
AB  - PMA and thrombin were examined for their ability to activate Na+/H+ exchange in
      growth-arrested WS-1 human fibroblasts. PMA or thrombin caused a cytoplasmic
      alkalinization that required extracellular sodium and was sensitive to 1 mM
      amiloride, suggesting that the rise in pH was mediated by the Na+/H+ exchanger.
      However, PMA and thrombin activated Na+/H+ exchange by distinctly different
      mechanisms. The rate of cytoplasmic alkalinization caused by 30 nM PMA was slower
      than 10 nM thrombin. The PMA-induced pH change was sensitive to the protein
      kinase inhibitors staurosporine (50 nM) and H-7 (100 microM). No increase in
      intracellular calcium was observed after PMA treatment and the cytoplasmic
      alkalinization caused by PMA was not sensitive to the drug TMB8 (200 microM) or
      the intracellular calcium-chelator BAPTA. In contrast, the thrombin-induced rise
      in cytoplasmic pH was insensitive to 50 nM staurosporine and only partially
      reduced with 100 microM H-7. The thrombin-induced activation of Na+/H+ exchange
      was inhibited by 200 microM TMB8 or pretreatment with BAPTA. PMA caused
      translocation of PKC activity from a cytoplasmic to membrane fraction whereas
      thrombin did not. Pretreatment with 50 nM staurosporine significantly reduced
      measurable PKC activity with or without PMA treatment. PMA and thrombin were also
      examined for their ability to induce DNA synthesis in growth-arrested WS-1 human
      fibroblasts. Unlike thrombin, PMA did not stimulate [3H]-thymidine incorporation
      in cells serum-deprived for 48 hours. In addition, PMA inhibited thrombin-induced
      DNA synthesis when added at the same time or as late as 10 hours after thrombin
      addition. Therefore, thrombin and PMA activate Na+/H+ exchange by distinct
      pathways, but only the thrombin-induced pathway correlates with a mitogenic
      response.

PMID- 1999478
TI  - Regulation of glucose transport as well as glucose transporter and immediate
      early gene expression in 3T3-L1 preadipocytes by 8-bromo-cAMP.
AB  - In the present study we have examined the ability of 8-bromoadenosine cyclic
      3',5'-phosphate (8-bromo-cAMP; the membrane permeant analog of cAMP which can
      activate protein kinase A) to mimic hormone action and stimulate glucose
      transport and glucose transporter (GLUT-1) gene expression as well as the
      expression of several growth-related protooncogenes in quiescent 3T3-L1
      fibroblasts. 8-Bromo-cAMP induced a rapid and prolonged increase in the rate of
      hexose transport. Early activation of hexose transport (within 30 min) was
      associated with increased plasma membrane immunoreactive glucose transporters,
      which corresponded to a doubling in the number of D-glucose-displaceable, plasma
      membrane cytochalasin B binding sites. The time course for 8-bromo-cAMP-induced
      hexose transport preceded the accumulation of GLUT-1 mRNA, which peaked between 4
      and 8 h after exposure to the agent, and subsequently declined to approach basal
      (control) levels. Expression of the immediate-early genes c-fos and jun-B was
      induced by 8-bromo-cAMP on a rapid, but sustained time course, whereas induction
      of c-jun expression was delayed. Alterations in specific mRNAs following exposure
      to 8-bromo-cAMP were due to increased gene transcription (as judged by nuclear
      transcription run-on assays), although with respect to GLUT-1, an increase in
      mRNA stability was also observed. Treatment of the cells with forskolin resulted
      in the induction of GLUT-1 expression as well as expression of the immediate
      early genes. Exposure of quiescent 3T3-L1 fibroblasts to 8-bromo-cAMP resulted in
      a substantial increase in rates of total protein and RNA synthesis, but had
      little effect on DNA synthesis. The results demonstrate that 8-bromo-cAMP
      initiated a G0/G1 transition, but did not permit progression into S-phase. The
      results further suggest that increased cytosolic cAMP results in the stimulation
      of glucose transport by three distinct mechanisms to include translocation of pre
      existing transporters, increased transcription of the GLUT-1 gene and increased
      stability of GLUT-1 mRNA.

PMID- 1999479
TI  - Epidermal growth factor-induced hydrolysis of phosphatidylcholine by
      phospholipase D and phospholipase C in human dermal fibroblasts.
AB  - The enzymatic pathways for formation of 1,2-diradylglyceride in response to
      epidermal growth factor in human dermal fibroblasts have been investigated. 1,2
      Diradylglyceride mass was elevated 2-fold within one minute of addition of EGF.
      Maximal accumulation (4-fold) occurred at 5 minutes. Since both diacyl and ether
      linked diglyceride species occur naturally and may accumulate following agonist
      activation, we developed a novel method to determine separately the alterations
      in diacyl and ether-linked diglycerides following stimulation of fibroblasts with
      EGF. Utilizing this method, it was found that approximately 80% of the total
      cellular 1,2-diradylglyceride was diacyl, the remaining 20% being ether-linked.
      Addition of EGF caused accumulation of 1,2-diacylglyceride without alteration in
      the level of ether-linked diglyceride. Thus, the observed induction of 1,2
      diradylglyceride by EGF was due exclusively to increased formation of 1,2
      diacylglyceride. In cells labelled with [3H]choline, the water soluble
      phosphatidylcholine hydrolysis products, phosphorylcholine and choline, were
      increased 2-fold within 5 minutes of addition of EGF. No hydrolysis of
      phosphatidylethanolamine, phosphatidylserine, or phosphatidylinositol was
      observed. Quantitation by radiolabel and mass revealed equivalent elevations in
      phosphorylcholine and choline, suggesting stimulation of both phospholipase C and
      phospholipase D activities. To identify the presence of EGF-induced phospholipase
      D activity, cells were labelled with exogenous [3H]1-0-hexadecyl, 2-acyl
      phosphatidylcholine and its conversion to phosphatidic acid in response to EGF
      determined. Radiolabelled phosphatidic acid was detectable in 15 seconds after
      addition of EGF and was maximal (3-fold) at 30 seconds. Consistent with the
      presence of EGF-induced phospholipase D activity, treatment of cells with EGF, in
      the presence of [14C]ethanol, resulted in the rapid formation of
      [14C]phosphatidylethanol, the product of phospholipase D-catalyzed
      transphosphatidylation. The formation of phosphatidylethanol, which competes for
      the formation of phosphatidic acid by phospholipase D, did not diminish the
      induction of 1,2-diglyceride by EGF. These data suggest that the phosphatidic
      acid formed by phospholipase D-catalyzed hydrolysis of phosphatidylcholine is not
      a major precursor of the observed increased 1,2-diglyceride. Thus, the induction
      of 1,2-diacylglycerol by EGF may occur primarily via phospholipase C-catalyzed
      hydrolysis of phosphatidylcholine.

PMID- 1999480
TI  - Arterial mechanical properties in dilated cardiomyopathy. Aging and the response
      to nitroprusside.
AB  - The effects of aging on arterial mechanical properties and the response to
      nitroprusside were examined in 25 patients with dilated cardiomyopathy. High
      fidelity pressures were recorded with a multisensor catheter. Pulse wave velocity
      was determined between two sensors in the thoracic aorta. Arterial compliance was
      determined by an analysis of the diastolic waveform and cardiac output. At
      baseline, despite a similar systemic vascular resistance, the pulsatile load
      (e.g., arterial compliance) and wave transmission characteristics (e.g., pulse
      wave velocity) were altered with aging. Arterial compliance was reduced in older
      (greater than 50 yr, n = 8) versus younger (less than 35 yr, n = 8) patients
      (0.51 +/- 0.17 vs. 1.33 +/- 0.63 ml/mmHg, P less than 0.01) and intermediate in
      those 35-50 yr of age (n = 9, 0.72 +/- 0.40 ml/mmHg). There was a positive
      correlation between age and pulse wave velocity (r = +0.90). Nitroprusside
      infusion decreased resistance, increased arterial compliance, and lowered pulse
      wave velocity in all groups. Yet, advancing age was associated with a greater
      fall in wave velocity for a given fall in aortic pressure. The slope (K) of the
      relation between pulse wave velocity and aortic diastolic pressure progressively
      increased with age (0.01 +/- 0.03, 0.06 +/- 0.02, and 0.09 +/- 0.03 m/s-mmHg).
      Multiple linear regression analysis revealed a significant relation between K and
      age. These data demonstrate that in older patients with dilated cardiomyopathy
      the left ventricle is coupled to an arterial circulation that has a greater
      pulsatile load, despite a similar steady load. Furthermore, these age-related
      changes in the arterial system affect the hemodynamic response to
      pharmacologically-induced vasodilatation.

PMID- 1999481
TI  - Transforming growth factor-beta and suppression of humoral immune responses in
      HIV infection.
AB  - We reported previously that PBMC from HIV+ patients spontaneously release
      increased levels of TGF beta 1, contributing to defects in cellular immune
      responses. This study defines the implications of TGF beta overexpression for
      humoral immunity in HIV infection. We found that upon Staphylococcus aureus Cowan
      I (SAC) stimulation of cells from HIV+ donors, B-lymphocyte proliferative
      responses were decreased. This deficiency correlated closely (r = 0.7, P less
      than 0.001) with increased TGF beta secretion by PBMC from HIV-infected donors.
      Conditioned medium from HIV+ PBMC and purified TGF beta 1 had similar inhibitory
      effects on SAC- or EBV-induced B-cell proliferation, and B cells from HIV
      infected donors were as sensitive to inhibition by TGF beta as cells from normal
      donors. Antibodies to TGF beta 1 neutralized the inhibitory effect of HIV+
      culture supernatants on normal B cells and increased low proliferative responses
      by HIV+ cells. Using PWM as stimulus for B cell differentiation, it was shown
      that activated TGF beta from HIV+ PBMC is able to significantly reduce the
      induction of immunoglobulins and this effect was also abrogated by anti-TGF beta.
      These studies support the concept that in HIV infection, TGF beta is a potent
      suppressor, not only of the cellular, but of the humoral immune responses as
      well.

PMID- 1999482
TI  - Activation of skeletal muscle casein kinase II by insulin is not diminished in
      subjects with insulin resistance.
AB  - Insulin resistance, which may precede the development of non-insulin-dependent
      diabetes mellitus in Pima Indians, appears to result from a postreceptor defect
      in signal transduction in skeletal muscle. To identify the putative postreceptor
      lesion responsible for insulin resistance in Pima Indians, we investigated the
      influence of insulin on the activity of casein kinase II (CKII) in skeletal
      muscle of seven insulin-sensitive, four insulin-resistant, nondiabetic, and five
      insulin-resistant diabetic Pima Indians during a 2 h hyperinsulinemic, euglycemic
      clamp. In sensitive subjects, CKII was transiently activated reaching a maximum
      over basal activity (42%) at 45 min before declining. CKII was also stimulated in
      resistant (19%) and diabetic (34%) subjects. Basal CKII activity in resistant
      subjects was 40% higher than in either sensitive or diabetic subjects, although
      the concentration of CKII protein, as determined by Western blotting, was equal
      among the three groups. Basal CKII activity was correlated with fasting plasma
      insulin concentrations, suggesting that the higher activity in resistant subjects
      resulted from insulin action. Extracts of muscle obtained from all three groups
      either before or after insulin administration were treated with immobilized
      alkaline phosphatase, which reduced and equalized CKII activity. These results
      suggest that insulin stimulates CKII activity in human skeletal muscle by a
      mechanism involving phosphorylation of either CKII or of an effector molecule,
      and support the idea that elevated basal activity in resistant subjects results
      from insulin action. It appears that the ability of insulin to activate CKII in
      skeletal muscle is not impaired in insulin-resistant Pima Indians, and that the
      biochemical lesion responsible for insulin resistance occurs either downstream
      from CKII or in a different pathway of insulin action.

PMID- 1999483
TI  - Diastolic dysfunction in hypertrophic cardiomyopathy. Effect on active force
      generation during systole.
AB  - We tested the hypothesis that intracellular Ca++ [( Ca++]i) overload underlies
      the diastolic dysfunction of patients with hypertrophic cardiomyopathy.
      Myocardial tissue was obtained at the time of surgery or transplantation from
      patients with hypertrophic cardiomyopathy and was compared with control
      myocardium obtained from patients without heart disease. The isometric
      contractions and electrophysiologic properties of all myocardial specimens were
      recorded by standard techniques and [Ca++]i was measured with the bioluminescent
      calcium indicator aequorin. In contrast to the controls, action potentials, Ca++
      transients, and isometric contraction and relaxation were markedly prolonged in
      the hypertrophic myocardium, and the Ca++ transients consisted of two distinct
      components. At 38 degrees C and 1 Hz pacing frequency, a state of relative Ca++
      overload appeared develop, which produced a rise in end-diastolic [Ca++]i,
      incomplete relaxation, and fusion of twitches with a resultant decrease in active
      tension development. We also found that drugs with increase [Ca++]i, such as
      digitalis, exacerbated these abnormalities, whereas drugs that lower [Ca++]i,
      such as verapamil, or agents that increase cyclic AMP, such as forskolin,
      prevented them. These results may explain why patients with hypertrophic
      cardiomyopathy tolerate tachycardia poorly, and may have important implications
      with regard to the pharmacologic treatment of patients with hypertrophic
      cardiomyopathy.

PMID- 1999484
TI  - Mucin production by human colonic carcinoma cells correlates with their
      metastatic potential in animal models of colon cancer metastasis.
AB  - Patients with mucinous colorectal cancers characteristically present with
      advanced disease, however, the relationship between mucin production by colon
      cancer cells and their metastatic potential remains unclear. We therefore sought
      to define the relationship between mucin production by human colon cancer cells
      and metastatic ability by employing animal models of colon cancer metastasis. LS
      LiM 6, a colon carcinoma cell line with high liver metastasizing ability during
      cecal growth in nude mice produced twofold more metabolically labeled
      intracellular mucin and secreted four- to fivefold more mucin into the culture
      medium compared to poorly metastatic parental line LS174T. This was accompanied
      by a similar elevation in poly(A)+ RNA detected by blot hybridization with a
      human intestinal mucin cDNA probe, and increases in mucin core carbohydrate
      antigens determined immunohistochemically. Variants of LS174T selected for high
      (HM 7) or low (LM 12) mucin synthesizing capacity also yielded metastases after
      cecal growth and colonized the liver after splenic-portal injection in proportion
      to their ability to produce mucin. Inhibition of mucin glycosylation by the
      arylglycoside benzyl-alpha-N-acetyl-galactosamine greatly reduced liver
      colonization after splenic-portal injection of the tumor cells. These data
      suggest that mucin production by human colon cancer cells correlates with their
      metastatic potential and affects their ability to colonize the liver in
      experimental model systems.

PMID- 1999485
TI  - Vaccination with Legionella pneumophila membranes induces cell-mediated and
      protective immunity in a guinea pig model of Legionnaires' disease. Protective
      immunity independent of the major secretory protein of Legionella pneumophila.
AB  - We have examined the capacity of Legionella pneumophila membranes to induce cell
      mediated immune responses and protective immunity in a guinea pig model of
      Legionnaires' disease. Guinea pigs immunized by aerosol with L. pneumophila
      membranes developed strong cell-mediated immune responses to L. pneumophila
      membranes as demonstrated by cutaneous delayed-type hypersensitivity and in vitro
      splenic lymphocyte proliferation. Guinea pigs immunized by aerosol or by
      subcutaneous inoculation with L. pneumophila membranes developed strong
      protective immunity against lethal aerosol challenge with L. pneumophila.
      Overall, in six independent experiments, 39 of 49 (80%) guinea pigs immunized
      with L. pneumophila membranes survived challenge compared with 2 of 40 (5%) sham
      immunized controls (P = 2 x 10(-13). In contrast, guinea pigs immunized by
      aerosol with formalin-killed L. pneumophila did not develop either a strong cell
      mediated immune response to L. pneumophila antigens or protective immunity to
      lethal aerosol challenge. The capacity of L. pneumophila membranes to induce
      protective immunity was independent of the major secretory protein of L.
      pneumophila, which we previously demonstrated is an immunoprotective molecule.
      Purified L. pneumophila membranes did not contain detectable major secretory
      protein (MSP) on immunoblots; immunization of guinea pigs with L. pneumophila
      membranes did not induce anti-MSP antibody; and guinea pigs developed comparable
      protective immunity after immunization with membranes from either an L.
      pneumophila strain that secretes the major secretory protein or an isogenic
      mutant that does not. This study demonstrates that (a) immunization with L.
      pneumophila membranes but not formalin-killed L. pneumophila induces strong cell
      mediated immune responses and protective immunity, (b) L. pneumophila membranes
      contain immunoprotective molecules distinct from the major secretory protein of
      L. pneumophila, and (c) L. pneumophila membranes have potential as a vaccine
      against Legionnaires' disease.

PMID- 1999486
TI  - Risk factors for emphysema. Cigarette smoking is associated with a reduction in
      the association rate constant of lung alpha 1-antitrypsin for neutrophil
      elastase.
AB  - The increased risk of developing emphysema among individuals who smoke cigarettes
      and who have normal levels of alpha 1-antitrypsin (alpha 1AT) is hypothesized to
      result from a decrease in the antineutrophil elastase capacity of the lower
      respiratory tract alpha 1AT of smokers compared with nonsmokers. To evaluate this
      hypothesis we compared the time-dependent kinetics of the inhibition of
      neutrophil elastase by lung alpha 1AT from healthy, young cigarette smokers (n =
      8) and nonsmokers (n = 12). alpha 1-antitrypsin was purified from lavage fluid
      using affinity and molecular sieve chromatography, and the association rate
      constant (k assoc) for neutrophil elastase quantified. The k assoc of smoker
      plasma alpha 1AT (9.5 +/- 0.5 X 10(6) M-1s-1) was similar to that of nonsmoker
      plasma (9.3 +/- 0.7 X 10(6) M-1s-1, P greater than 0.5). In marked contrast, the
      k assoc of smoker lower respiratory tract alpha 1AT was significantly lower than
      that of nonsmoker alpha 1AT (6.5 +/- 0.4 X 10(6) M-1s-1 vs. 8.1 +/- 0.5 X 10(6) M
      1s-1, P less than 0.01). Furthermore, the smoker lower respiratory tract alpha
      1AT k assoc was significantly less than that of autologous plasma (P less than
      0.01). When considered in the context of the concentration of alpha 1AT in the
      lower respiratory tract epithelial lining fluid, the inhibition time for
      neutrophil elastase of smoker lung alpha 1AT was twofold greater than that of
      nonsmoker lung alpha 1AT (smoker: 0.34 +/- 0.05 s vs. nonsmoker: 0.17 +/- 0.05 s,
      P less than 0.01). Consequently, for concentrations of alpha 1AT in the lower
      respiratory tract it takes twice as long for an equivalent amount of neutrophil
      elastase to be inhibited in the smoker's lung compared with the nonsmoker's lung.
      These observations support the concept that cigarette smoking is associated with
      a decrease in the lower respiratory tract neutrophil elastase inhibitory
      capacity, thus increasing the vulnerability of the lung to elastolytic
      destruction and thereby increasing the risk for the development of emphysema.

PMID- 1999487
TI  - Human keratinocytes produce but do not process pro-interleukin-1 (IL-1) beta.
      Different strategies of IL-1 production and processing in monocytes and
      keratinocytes.
AB  - Keratinocytes comprise the majority of cells in the epidermis, the interleukin-1
      rich layer of tissue contiguous with the outside world. Keratinocytes produce IL
      1 alpha and beta mRNA in vitro, but only IL-1 alpha biological activity has been
      identified in keratinocyte cultures. In contrast, monocytes secrete biological
      activities attributable to both species of IL-1. Using several monoclonal
      antibodies to IL-1 beta, significant amounts of IL-1 beta protein could be found
      in keratinocyte cultures; all of this immunoreactive IL-1 beta was in the 31-kD
      form. This latent cytokine has been shown to bind inefficiently to the IL-1
      receptor and to be (in relative terms) biologically inactive. Chymotrypsin
      cleaves 31-kD IL-1 beta at Tyr 113-Val 114, generating an 18-kD IL-1 species with
      activity equivalent to the authentic mature IL-1 beta (NH2-terminal Ala 117).
      Treatment of 31-kD keratinocyte IL-1 beta with chymotrypsin also generated an 18
      kD molecule and significant IL-1 activity. Monocytes contain an IL-1 convertase
      enzyme that cleaves the IL-1 beta promolecule at Ala 117. We demonstrate here
      that keratinocytes do not contain such an IL-1 convertase activity, nor do they
      contain any activity capable of productively processing 31-kD IL-1 beta into a
      biologically active form. These data suggest that keratinocytes (and other non
      bone marrow-derived cells) produce IL-1 beta in an inactive form that can be
      processed only after leaving the cell.

PMID- 1999489
TI  - Recurrent nonsense mutations in the growth hormone receptor from patients with
      Laron dwarfism.
AB  - In addition to its classical effects on growth, growth hormone (GH) has been
      shown to have a number of other actions, all of which are initiated by an
      interaction with specific high affinity receptors present in a variety of
      tissues. Purification of a rabbit liver protein via its ability to bind GH has
      allowed the isolation of a cDNA encoding a putative human growth hormone receptor
      that belongs to a new class of transmembrane receptors. We have previously shown
      that this putative growth hormone receptor gene is genetically linked to Laron
      dwarfism, a rare autosomal recessive syndrome caused by target resistance to GH.
      Nevertheless, the inability to express the corresponding full-length coding
      sequence and the lack of a test for growth-promoting function have hampered a
      direct confirmation of its role in growth. We have now identified three nonsense
      mutations within this growth hormone receptor gene, lying at positions
      corresponding to the amino terminal extremity and causing a truncation of the
      molecule, thereby deleting a large portion of both the GH binding domain and the
      full transmembrane and intracellular domains. Three independent patients with
      Laron dwarfism born of consanguineous parents were homozygous for these defects.
      Two defects were identical and consisted of a CG to TG transition. Not only do
      these results confirm the growth-promoting activity of this receptor but they
      also suggest that CpG doublets may represent hot spots for mutations in the
      growth hormone receptor gene that are responsible for hereditary dwarfism.

PMID- 1999488
TI  - Pretranslational suppression of a glucose transporter protein causes insulin
      resistance in adipocytes from patients with non-insulin-dependent diabetes
      mellitus and obesity.
AB  - A major portion of insulin-mediated glucose uptake occurs via the translocation
      of GLUT 4 glucose transporter proteins from an intracellular depot to the plasma
      membrane. We have examined gene expression for the GLUT 4 transporter isoform in
      subcutaneous adipocytes, a classic insulin target cell, to better understand
      molecular mechanisms causing insulin resistance in non-insulin-dependent diabetes
      mellitus (NIDDM) and obesity. In subgroups of lean (body mass index [BMI] = 24 +/
      1) and obese (BMI = 32 +/- 2) controls and in obese NIDDM (BMI = 35 +/- 2)
      patients, the number of GLUT 4 glucose transporters was measured in total
      postnuclear and subcellular membrane fractions using specific antibodies on
      Western blots. Relative to lean controls, the cellular content of GLUT 4 was
      decreased 40% in obesity and 85% in NIDDM in total cellular membranes. In
      obesity, cellular depletion of GLUT 4 primarily involved low density microsomes
      (LDM), leaving fewer transporters available for insulin-mediated recruitment to
      the plasma membrane (PM). In NIDDM, loss of GLUT 4 was profound in all membrane
      subfractions, PM, LDM, as well as high density microsomes. These observations
      corresponded with decrements in maximally stimulated glucose transport rates in
      intact cells. To assess mechanisms responsible for depletion of GLUT 4, we
      quantitated levels of mRNA specifically hybridizing with human GLUT 4 cDNA on
      Northern blots. In obesity, GLUT 4 mRNA was decreased 36% compared with lean
      controls, and the level was well correlated (r = + 0.77) with the cellular
      content of GLUT 4 protein over a wide spectrum of body weight. GLUT 4 mRNA in
      adipocytes from NIDDM patients was profoundly reduced by 86% compared with lean
      controls and by 78% relative to their weight-matched nondiabetic counterparts
      (whether expressed per RNA, per cell, or for the amount of CHO-B mRNA).
      Interestingly, GLUT 4 mRNA levels in patients with impaired glucose tolerance
      (BMI = 34 +/- 4) were decreased to the same level as in overt NIDDM. We conclude
      that, in obesity, insulin resistance in adipocytes is due to depletion of GLUT 4
      glucose transporters, and that the cellular content of GLUT 4 is determined by
      the level of encoding mRNA over a wide range of body weight. In NIDDM, more
      profound insulin resistance is caused by a further reduction in GLUT 4 mRNA and
      protein than is attributable to obesity per se. Suppression of GLUT 4 mRNA is
      observed in patients with impaired glucose tolerance, and therefore, may occur
      early in the evolution of diabetes. Thus, pretranslational suppression of GLUT 4
      transporter gene expression may be an important mechanism that produces and
      maintains cellular insulin resistance in NIDDM.

PMID- 1999490
TI  - Transforming growth factor beta 1 suppresses acute and chronic arthritis in
      experimental animals.
AB  - Systemic administration of the cytokine, TGF beta 1, profoundly antagonized the
      development of polyarthritis in susceptible rats. TGF beta 1 administration (1 or
      5 micrograms/animal), initiated one day before an arthritogenic dose of
      streptococcal cell wall (SCW) fragments, virtually eliminated the joint swelling
      and distortion typically observed during both the acute phase (articular index,
      AI = 2.5 vs. 11; P less than 0.025) and the chronic phase (AI = 0 vs. 12.5) of
      the disease. Moreover, TGF beta 1 suppressed the evolution of arthritis even when
      administration was begun after the acute phase of the disease. Histopathological
      examination of the joint revealed the systemic TGF beta 1 treatment greatly
      reduced inflammatory cell infiltration, pannus formation, and joint erosion.
      Consistent with the inhibition of inflammatory cell recruitment into the
      synovium, TGF beta 1 reversed the leukocytosis associated with the chronic phase
      of the arthritis. Control animals subjected to the same TGF beta 1 dosing regimen
      displayed no discernable immunosuppressive or toxic effects even after 4 wk of
      treatment. These observations not only provide insight into the immunoregulatory
      effects of TGF beta, but also implicate this cytokine as a potentially important
      therapeutic agent.

PMID- 1999491
TI  - A mutation in the DNA-binding domain of the androgen receptor gene causes
      complete testicular feminization in a patient with receptor-positive androgen
      resistance.
AB  - Androgen resistance is associated with a wide range of quantitative and
      qualitative defects in the androgen receptor. However, fibroblast cultures from
      approximately 10% of patients with the clinical, endocrine, and genetic features
      characteristic of androgen resistance express normal quantities of apparently
      normal androgen receptor in cultured genital skin fibroblasts (receptor-positive
      androgen resistance). We have analyzed the androgen receptor gene of one patient
      (P321) with receptor-positive, complete testicular feminization and detected a
      single nucleotide substitution at nucleotide 2006 (G----C) within the second
      "zinc finger" of the DNA-binding domain that results in the conversion of the
      arginine residue at position 615 into a proline residue. Introduction of this
      mutation into the androgen receptor cDNA and transfection of the expression
      plasmid into eukaryotic cells lead to the synthesis of a receptor protein that
      displays normal binding kinetics but is inactive in functional assays of receptor
      activity. We conclude that substitution mutations in the DNA-binding domain of
      the androgen receptor are one cause of "receptor-positive" androgen resistance.

PMID- 1999492
TI  - Differential regulation of adipose tissue glucose transporters in genetic obesity
      (fatty rat). Selective increase in the adipose cell/muscle glucose transporter
      (GLUT 4) expression.
AB  - Adipocytes from young obese Zucker rats exhibit a hyperresponsive insulin
      mediated glucose transport, together with a marked increase in cytochalasin B
      binding as compared with lean rat adipocytes. Here, we examined in these cells
      the expression of two isoforms of glucose transporter, the erythroid (GLUT 1) and
      the adipose cell/muscle (GLUT 4) types, in rats aged 16 or 30 d, i.e., before and
      after the emergence of hyperinsulinemia. GLUT 1 protein and mRNA levels were
      identical in the two genotypes at both ages. In contrast, the levels of GLUT 4
      protein in obese rat adipocytes were 2.4- and 4.5-fold those of lean littermates
      at 16 and 30 d of age, respectively, in perfect agreement with the genotype
      effect on insulin-stimulated glucose transport activity. The levels of GLUT 4
      mRNA per fat pad were increased 2.3- and 6.2-fold in obese vs. lean rats 16- and
      30-d-old, indicating a pretranslational level of regulation. The obese phenotype
      was not associated with overexpression of GLUT 4 mRNA in gastrocnemius muscle.
      This work indicates that the fa gene exerts a differential control on the
      expression of GLUT 1 and GLUT 4 in adipose tissue and provides evidence that
      independent of hyperinsulinemia, genotype is a major regulatory factor of GLUT 4
      expression in this tissue.

PMID- 1999493
TI  - Molecular biology of the type I human T-cell leukemia virus (HTLV-I) and adult T
      cell leukemia.

PMID- 1999494
TI  - Acquired cisplatin resistance in human ovarian cancer cells is associated with
      enhanced repair of cisplatin-DNA lesions and reduced drug accumulation.
AB  - Studies were undertaken to investigate acquired resistance to cisplatin in human
      ovarian cancer cells. The cell lines A2780 and A2780/CP70 were studied to assess
      their respective characteristics of drug accumulation and efflux, cytosolic
      inactivation of drug, and DNA repair. All experiments were performed using 1-h
      drug exposures. The A2780/CP70 cell line was 13-fold more resistant to cisplatin
      than A2780 cells. When studied at their respective IC50 doses, drug accumulation
      rates were similar for the two cell lines. However, the resistant cell line was
      twofold more efficient at effluxing drug, which was associated with reduced total
      drug accumulation for equivalent micromolar drug exposures. At equivalent levels
      of total cellular drug accumulation, the two cell lines formed the same levels of
      cisplatin-DNA damage, suggesting that cytosolic inactivation of drug does not
      contribute to the differential in resistance between these cell lines. Resistant
      cells were also twofold more efficient at repairing cisplatin-DNA lesions in
      cellular DNA and in transfected plasmid DNA. We conclude that in these paired
      cell lines, alterations in drug uptake/efflux and in DNA repair are the major
      contributing factors to acquired resistance to cisplatin.

PMID- 1999495
TI  - Mycoplasma pulmonis infections cause long-lasting potentiation of neurogenic
      inflammation in the respiratory tract of the rat.
AB  - These experiments were done to learn whether Mycoplasma pulmonis infections of
      the respiratory tract of rats can potentiate "neurogenic inflammation" and
      whether this potentiation is amplified by factors that exacerbate the infections.
      Pathogen-free F344 rats were inoculated intranasally with M. pulmonis or with
      sterile culture medium and then lived for 4 wk in an ammonia-free atmosphere or
      in air containing ammonia (100 parts per million). Neurogenic inflammation was
      evoked by an intravenous injection of capsaicin, and 5 min later the magnitude of
      the response was quantified by measuring the amount of extravasation of two
      tracers, Monastral blue pigment and Evans blue dye. We found that vascular
      permeability in the tracheas of all rats was normal in the absence of capsaicin.
      However, a 75-micrograms/kg dose of capsaicin, which caused almost no
      extravasation of Evans blue in the tracheas of pathogen-free controls (17 +/- 3
      ng/mg; mean +/- SE), produced extensive extravasation in the infected rats (135
      +/- 18 ng/mg; P less than 0.001). Similarly, this dose of capsaicin produced 30
      times as much Monastral blue extravasation in the infected rats (area density =
      47 +/- 8% of surface area) as it did in the pathogen-free rats (1.6 +/- 0.5%; P
      less than 0.001), a difference that resulted from increases in the number of
      Monastral blue-labeled postcapillary venules and in the amount of labeling per
      venule. Exposure of the infected rats to ammonia exacerbated the infections,
      further increased the number of Monastral blue-labeled vessels and the amount of
      labeling per vessel, and made the rats so sensitive to capsaicin that a normally
      tolerable dose of 150 micrograms/kg i.v. caused fatal apnea. Ammonia did not have
      these effects in pathogen-free rats. We conclude that M. pulmonis infections of
      the airway mucosa cause a potent, long-lasting potentiation of neurogenic
      inflammation, which results in part from an increase in the number and
      responsiveness of mediator-sensitive postcapillary venules. These changes can be
      amplified by environmental factors such as ammonia which exacerbate the
      infections.

PMID- 1999496
TI  - Plasticity of integrin expression by nerve-derived connective tissue cells. Human
      Schwann cells, perineurial cells, and fibroblasts express markedly different
      patterns of beta 1 integrins during nerve development, neoplasia, and in vitro.
AB  - Strikingly selective expression patterns of beta 1, alpha 2, alpha 3, and alpha 5
      integrin subunits were revealed in endoneurium, perineurium, and epineurium of
      fetal and adult human peripheral nerve by immunostaining with specific
      antibodies. The alpha 2 subunit was expressed only on Schwann cells both in fetal
      and adult nerve, whereas the alpha 3 epitopes were expressed exclusively in the
      adult tissue and were primarily present on perineurial cells. The alpha 5
      epitopes were expressed only on the innermost cell layer of perineurium of fetal
      and adult nerve. The tumor cells within schwannomas and cutaneous neurofibromas
      expressed both alpha 2 and alpha 3 subunits, indicating that Schwann cells have
      the potential to express also the alpha 3 subunit in vivo. Cell cultures
      established from human fetal nerve and neurofibromas revealed expression of the
      alpha 2 and alpha 5 epitopes on Schwann cells, perineurial cells, and
      fibroblasts, whereas only Schwann cells contained the alpha 3 epitopes which were
      occasionally concentrated on the adjacent Schwann cells at cell-cell contacts.
      Our findings emphasize that nerve connective tissue cells change their profiles
      for expression of extracellular matrix receptors under conditions which have
      different regulatory control signals exerted by, for example, axons, humoral
      factors, or the extracellular matrix of the peripheral nerve. This plasticity may
      play an important role during nerve development and in neoplastic processes
      affecting the connective tissue compartments of peripheral nerve.

PMID- 1999497
TI  - Antibodies elicited by pneumococcal antigens bear an anti-DNA--associated
      idiotype.
AB  - There is evidence in both murine and human lupus that the production of anti-DNA
      antibodies may be triggered by environmental antigens. To explore this further,
      we studied the serum of 10 nonautoimmune individuals immunized with a polyvalent
      pneumococcal polysaccharide vaccine. All 10 patients showed a rise in the titer
      of antipneumococcal antibodies bearing an anti-DNA-associated idiotype. The
      antipneumococcal response was specific as no idiotypic antitetanus antibodies
      were detected. Furthermore, no anti-DNA antibodies were present in
      postvaccination sera. The molecular analysis of antipneumococcal and anti-DNA
      antibodies bearing a common idiotype will help elucidate how foreign antigen
      might lead to the production of anti-DNA antibodies in susceptible individuals.

PMID- 1999498
TI  - Infantile form of carnitine palmitoyltransferase II deficiency with
      hepatomuscular symptoms and sudden death. Physiopathological approach to
      carnitine palmitoyltransferase II deficiencies.
AB  - Reported cases of carnitine palmitoyltransferase II (CPT II) deficiency are
      characterized only by a muscular symptomatology in young adults although the
      defect is expressed in extra-muscular tissues as well as in skeletal muscle. We
      describe here a CPT II deficiency associating hypoketotic hypoglycemia, high
      plasma creatine kinase level, heart beat disorders, and sudden death in a 3-mo
      old boy. CPT II defect (-90%) diagnosed in fibroblasts is qualitatively similar
      to that (-75%) of two "classical" CPT II-deficient patients previously studied:
      It resulted from a decreased amount of CPT II probably arising from its reduced
      biosynthesis. Consequences of CPT II deficiency studied in fibroblasts differed
      in both sets of patients. An impaired oxidation of long-chain fatty acids was
      found in the proband but not in patients with the "classical" form of the
      deficiency. The metabolic and clinical consequences of CPT II deficiency might
      depend, in part, on the magnitude of residual CPT II activity. With 25% residual
      activity CPT II would become rate limiting in skeletal muscle but not in liver,
      heart, and fibroblasts. As observed in the patient described herein, CPT II
      activity ought to be more reduced to induce an impaired oxidation of long-chain
      fatty acids in these tissues.

PMID- 1999500
TI  - Hypoxia induces a specific set of stress proteins in cultured endothelial cells.
AB  - Vascular endothelial cells (EC) are the initial cells within the vascular wall
      exposed to decreases in blood ambient oxygen concentration. The mechanisms by
      which they tolerate low levels of oxygen are unknown, but may parallel the
      response to other cellular stresses, such as heat shock. After 4-8 h of hypoxia,
      we found a decrease in total protein synthesis in both cultured bovine aortic and
      pulmonary arterial EC. SDS-PAGE and autoradiographic analysis of [35S]methionine
      labeled proteins demonstrated the concomitant induction of a specific set of
      proteins (Mr 34, 36, 47, and 56 kD) in both cell types. These hypoxia-associated
      proteins (HAPs) were cell-associated and up-regulated in a time- and oxygen
      concentration-dependent manner. Comparison of these proteins with heat shock
      proteins (HSPs) demonstrated that HAPs were distinct from HSPs. EC maintained
      chronically in 3% O2 continued to synthesize elevated levels of HAPs, yet further
      up-regulated these proteins when exposed to 0% O2. The presence of five times the
      normal media glucose concentration did not alter the appearance of HAPs. Hypoxia
      sensitive renal tubular epithelial cells up-regulated no proteins corresponding
      to HAPs and were irreversibly damaged within 8 h of exposure to 0% O2. In vitro
      translation experiments demonstrated that the steady-state level of several mRNAs
      was higher in the anoxic EC than in normoxic EC and encoded for proteins of Mr
      32, 35, 37, 40, and 48 kD that were different from proteins encoded by HSP mRNAs.
      The induction of HAPs during acute hypoxia and their continued synthesis in
      chronic hypoxia suggest that HAPs may be important in the maintenance of
      endothelial cell integrity under conditions of decreased ambient oxygen.

PMID- 1999499
TI  - Regulation of parathyroid hormone-like peptide in cultured normal human
      keratinocytes. Effect of growth factors and 1,25 dihydroxyvitamin D3 on gene
      expression and secretion.
AB  - We have examined the expression and secretion of endogenous parathyroid hormone
      like peptide (PLP) in primary cultures of normal human keratinocytes. In response
      to growth factors and fetal bovine serum, PLP mRNA expression and immunoreactive
      PLP release into conditioned medium was rapidly increased (within hours) whereas
      these effects were inhibited by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. These
      early responses were not influenced by raising the medium calcium concentration
      from 0.15 to 1.0 mM. In contrast, increasing the medium calcium concentration to
      1.0 mM, addition of 1,25(OH)2D3, or a combination of both, resulted in a delayed
      augmentation (after several days) in PLP production which was associated with an
      increase in cellular differentiation as assessed by production of high molecular
      weight keratin. To investigate whether these factors were acting at the level of
      transcription of the PLP gene, a series of vectors were prepared by fusing
      segments of the 5' flanking region of the rat PLP gene to a growth hormone
      reporter gene. Transient transfection of these constructs into cultured
      keratinocytes and measurement of immunoreactive growth hormone in the medium
      showed that a region stimulated by growth factors is located in a 1.9-kb fragment
      of the 5' flanking region and that a PLP gene promoter region less than 1.2 kb
      and greater than 0.3 kb upstream of the cap site contains cis-acting elements
      which respond positively to serum, and negatively to 1,25(OH)2D3. These combined
      studies demonstrate that, in normal human keratinocytes, growth factors may
      acutely stimulate PLP mRNA levels and PLP release, whereas 1,25(OH)2D3 inhibits
      these responses. At least part of these effects are at the level of gene
      transcription. Additionally, PLP synthesis and release are enhanced under
      conditions in which keratinocyte differentiation is induced.

PMID- 1999501
TI  - Intraportal glucose delivery alters the relationship between net hepatic glucose
      uptake and the insulin concentration.
AB  - To examine the relationship between net hepatic glucose uptake (NHGU) and the
      insulin level and to determine the effects of portal glucose delivery on that
      relationship, NHGU was evaluated at three different insulin levels in seven 42-h
      fasted, conscious dogs during peripheral glucose delivery and during a
      combination of peripheral and portal glucose delivery. During peripheral glucose
      delivery, at arterial blood glucose levels of approximately 175 mg/dl and insulin
      levels reaching the liver of 51 +/- 2, 92 +/- 6, and 191 +/- 6 microU/ml,
      respectively, NHGUs were 0.55 +/- 0.30, 1.52 +/- 0.44, and 3.04 +/- 0.79 mg/kg
      per min, respectively. At hepatic glucose loads comparable to those achieved
      during peripheral glucose delivery and inflowing insulin levels of 50 +/- 4, 96
      +/- 5, and 170 +/- 8 microU per ml, respectively, NHGUs were 1.96 +/- 0.48, 3.67
      +/- 0.68, and 5.52 +/- 0.92 mg/kg per min when a portion of the glucose load was
      delivered directly into the portal vein. The results of these studies thus
      indicate that net hepatic glucose uptake is dependent on both the plasma insulin
      level and the route of glucose delivery and that under physiological conditions
      the "portal" signal is at least as important as insulin in the determination of
      net hepatic glucose uptake.

PMID- 1999502
TI  - Guanine ribonucleotide depletion inhibits T cell activation. Mechanism of action
      of the immunosuppressive drug mizoribine.
AB  - The immunosuppressive drug, mizoribine, has been used to prevent rejection of
      organ allografts in humans and in animal models. Based on studies in cell lines,
      mizoribine has been postulated to be an inhibitor of inosine monophosphate (IMP)
      dehydrogenase (EC1.2.1.14), a pivotal enzyme in the formation of guanine
      ribonucleotides from IMP. To further characterize the mechanism of action of this
      drug, we studied the effect of mizoribine on human peripheral blood T cells
      stimulated with alloantigen, anti-CD3 MAb, or pharmacologic mitogens. Mizoribine
      (1-50 micrograms/ml) was able to inhibit T cell proliferation by 10-100% in a
      dose-dependent fashion to all stimuli tested. Measurements of purine
      ribonucleotide pools by HPLC showed that mizoribine led to a decrease in
      intracellular GTP levels, and that repletion of GTP reversed its
      antiproliferative effects. We also examined sequential events occurring after T
      cell stimulation. Early events in T cell activation, as assessed by steady-state
      mRNA levels of c-myc, IL-2, c-myb, histone, and cdc2 kinase, as well as surface
      IL-2 receptor expression, were unaffected. However, cell cycle analysis revealed
      decreased numbers of cells in S, G2, and M phases, and showed that the G1/S block
      was reversed with GTP repletion. These data indicate that mizoribine has an
      effect on T cell proliferation by a mechanism distinct from that of cyclosporine
      or corticosteroids, and therefore may be useful in combination immunosuppressive
      regimens.

PMID- 1999503
TI  - Identification of lymphotoxin and tumor necrosis factor in multiple sclerosis
      lesions.
AB  - Multiple sclerosis (MS) brain tissue, spleen, and PBMC were studied using
      immunocytochemistry and FACS for immunoreactivity for lymphotoxin (LT) and TNF.
      Both cytokines were identified in acute and chronic active MS lesions but were
      absent from chronic silent lesions. LT was associated with CD3+ lymphocytes and
      Leu-M5+ microglia cells at the lesion edge and to a lesser extent, in adjacent
      white matter. TNF was associated with astrocytes in all areas of the lesion, and
      with foamy macrophages in the center of the active lesion. In acute lesions,
      immunoreactivity for TNF in endothelial cells was noted at the lesion edge. No LT
      or TNF reactivity was detected in Alzheimer's or Parkinson's disease brain
      tissues but was present at lower levels in central nervous system (CNS) tissue
      from other inflammatory conditions, except for adrenoleucodystrophy which
      displayed high levels of LT in microglia. No increase in LT and TNF reactivity
      was detected in spleen and PBMC of MS patients suggesting specific reactivity
      within the CNS. These results indicate that LT and TNF may be involved in the
      immunopathogenesis of MS, and can be detected in both inflammatory cells and
      cells endogenous to the CNS.

PMID- 1999504
TI  - Defective polymorphonuclear leukocyte formyl peptide receptor(s) in juvenile
      periodontitis.
AB  - Juvenile periodontitis (JP) is a disease characterized by severe gingival
      infections. PMN from some JP patients exhibit abnormal chemotactic responsiveness
      when challenged with the synthetic formyl peptide, FMLP. While investigating PMN
      function in JP, we found a patient in whom abnormal PMN chemotactic responses to
      FMLP were associated with a defective population of PMN formyl peptide
      receptor(s) (FPR). JP PMN failed to respond chemotactically when challenged with
      FMLP, but exhibited normal chemotactic responses upon exposure to purified human
      C5a. Furthermore, JP PMN were capable of degranulating and generating superoxide
      anion radicals as well as normal PMN upon exposure to FMLP. Binding studies
      demonstrated that JP PMN had a diminution in the number of high-affinity FPR.
      Studies in which FPR was radiolabeled by chemical cross-linking demonstrated that
      JP PMN FPR exhibited the same molecular weight and N-linked glycosylation as
      normal PMN FPR. JP PMN FPR, however, was more resistant to papain cleavage than
      normal PMN FPR. Autoradiograms obtained from 2D-PAGE of normal and JP PMN FPR
      demonstrated decreased amounts of FPR isoforms in JP PMN.

PMID- 1999506
TI  - Biology of basal cell carcinoma (Part I).
AB  - Basal cell carcinoma is the most common malignancy in humans. Although rarely
      metastatic, it is capable of significant local destruction and disfigurement.
      This two-part article reviews the current understanding of basal cell carcinoma
      biology. Part I examines significant clinical, histologic, and ultrastructural
      features that relate to invasive potential. Genetic characteristics, including
      tumor growth rate, chromosomal abnormalities, and oncogene presence, are
      discussed, and expression of important cell and matrix proteins, including
      keratin, fibronectin, and HLA antigens, are reviewed. Further topics to be
      explored in Part II include host immunologic responses, theories of pathogenesis,
      and valuable second-line therapeutic regimens for treatment of multiple cancers.

PMID- 1999507
TI  - The reliability of frozen sections in the evaluation of surgical margins for
      melanoma.
AB  - As the width of surgical margins declines, histologic evaluation of the margins
      is needed to assess the completeness of excision of a malignant melanoma. We
      studied 221 specimens in 59 patients and compared the interpretations of frozen
      and paraffin sections from the same block. Frozen sections had a sensitivity of
      100% in detecting melanoma when present and a specificity of 90%.

PMID- 1999505
TI  - Evidence that tumor necrosis factor plays a pathogenetic role in the
      paraneoplastic syndromes of cachexia, hypercalcemia, and leukocytosis in a human
      tumor in nude mice.
AB  - Recently, we have established a human squamous cell carcinoma of the maxilla
      (called MH-85) associated with hypercalcemia, leukocytosis, and cachexia in
      culture. MH-85 tumor cells caused the same paraneoplastic syndromes in tumor
      bearing nude mice. We found that there was a sixfold increase in splenic size in
      MH-85 tumor-bearing mice. This increase paralleled tumor growth and was reversed
      by surgical removal of the tumor. Splenectomy in nude mice 1 wk before or 6 wk
      after tumor inoculation resulted in a decrease in tumor growth, and impairment of
      hypercalcemia, leukocytosis, and cachexia. In MH-85 tumor-bearing animals that
      had been pretreated by splenectomy, intravenous injection of fresh normal spleen
      cells caused an immediate reversal of leukocytosis, hypercalcemia, and cachexia.
      Since the presence of cachexia in both the patient and the mice carrying the
      tumor suggested tumor necrosis factor (TNF) may be overproduced, we injected
      polyclonal neutralizing antibodies raised against murine TNF into tumor-bearing
      mice. There was a rapid and reproducible decrease in blood ionized calcium,
      accompanied by suppression of osteoclast activity. No changes in blood ionized
      calcium were seen in mice injected with normal immune sera. In addition, there
      was an increase in body weight and decrease in white cell count. Plasma
      immunoreactive TNF was increased almost fourfold in tumor-bearing nude mice
      compared with control nude mice. Although TNF activity was undetectable in MH-85
      culture supernatants, cells of the macrophage lineage, including spleen cells,
      released increased amounts of TNF when cultured with MH-85 tumor-conditioned
      media. These results suggest that splenic cytokines such as TNF may influence the
      development of the paraneoplastic syndromes of hypercalcemia, leukocytosis, and
      cachexia in these animals, as well as tumor growth. They also show that
      paraneoplastic syndromes may be due to factors produced by normal host cells
      stimulated by the presence of the tumor.

PMID- 1999508
TI  - Congenital immunodeficiency syndromes with cutaneous manifestations. II.

PMID- 1999509
TI  - Revised clinical and laboratory criteria for subtypes of inherited epidermolysis
      bullosa. A consensus report by the Subcommittee on Diagnosis and Classification
      of the National Epidermolysis Bullosa Registry.
AB  - Inherited epidermolysis bullosa encompasses a number of diseases, with the common
      finding of blister formation after minor mechanical trauma to the skin. In some
      forms significant, if not eventually fatal, extracutaneous disease activity may
      occur. In recent years application of newer technologies has contributed
      substantially to an overall understanding of this collection of inherited
      diseases. Concurrently, many new phenotypes have been recognized, in part the
      result of ongoing prospective patient registries in the United States and abroad.
      Unfortunately, this has resulted in a massive literature that may appear to be
      confounded by seemingly excessive or arbitrary subdivision of epidermolysis
      bullosa variants. With these concerns in mind a subcommittee was established by
      the National Epidermolysis Bullosa Registry to summarize the current literature
      and to make recommendations as to the best clinical and laboratory criteria for
      the practical diagnosis and subclassification of patients with inherited
      epidermolysis bullosa.

PMID- 1999511
TI  - Nodular vulvar amyloid as a presentation of systemic amyloidosis.

PMID- 1999510
TI  - International symposium on cutaneous T cell lymphoma. Chicago, Illinois, Oct. 19
      21, 1989.

PMID- 1999512
TI  - Sweet's syndrome presenting as an unusual periorbital eruption.

PMID- 1999513
TI  - Cyclosporine treatment of pyoderma gangrenosum.

PMID- 1999514
TI  - Treatment of primary erythromelalgia with piroxicam.

PMID- 1999515
TI  - Figure eight closure.

PMID- 1999516
TI  - Eschars and scarring from hot needle acupuncture treatment.

PMID- 1999517
TI  - Danger of needle cap piercing injury.

PMID- 1999518
TI  - Topical mercury should be banned--dangerous, outmoded, but still popular.

PMID- 1999520
TI  - Patch testing and the menstrual cycle.

PMID- 1999521
TI  - Historical differentiation between erythromelalgia and causalgia.

PMID- 1999519
TI  - Bullous pemphigoid and psoriasis: treatment with cyclosporine.

PMID- 1999522
TI  - Cutaneous manifestations of immunosuppression in organ transplant recipients.

PMID- 1999523
TI  - CD45R antigen is expressed on eosinophils in paraffin-embedded tissue sections.

PMID- 1999524
TI  - Infantile acute hemorrhagic edema of the skin: study of ten cases.
AB  - Infantile acute hemorrhagic edema of the skin is not included as a separate
      entity in the current English-language literature as it is in continental Europe.
      Therefore we have attempted to clarify the nosologic position of acute
      hemorrhagic edema among cutaneous vasculitides in children, on the basis of our
      experience in 10 cases. Our study confirms that acute hemorrhagic edema affects
      infants between 4 and 24 months of age. The two main features are an ecchymotic
      purpura, often in a cockade pattern, and an inflammatory edema of the limbs and
      face. Visceral involvement is uncommon. Spontaneous and complete resolution
      occurs within 1 to 3 weeks; one to four attacks may occur. Histopathologic
      examination demonstrates a leukocytoclastic vasculitis. Perivascular IgA deposits
      can occasionally be found. Besides typical acute hemorrhagic edema, some cases in
      2- to 4-year-old children appear to overlap with Schonlein-Henoch purpura. We
      suggest that typical acute hemorrhagic edema should be regarded as a separate
      clinical entity. This allows an appropriate prognosis to be made for this
      generally benign disease of infants.

PMID- 1999525
TI  - Epidermotropic eccrine porocarcinoma.
AB  - Three cases of epidermotropic eccrine porocarcinoma are summarized and compared
      with reported cases. All patients had a long-standing tumor on a lower extremity
      that rapidly metastasized to the skin and proximal lymph nodes. The histologic
      picture was consistent with an intraepidermal eccrine sweat gland carcinoma.

PMID- 1999526
TI  - Langerhans cell histiocytosis in monozygotic twins.
AB  - Langerhans cells histiocytosis, one of a group of histiocytosis syndromes
      characterized by Langerhans cell infiltration, has many clinical manifestations.
      In the past 30 years, numerous cases of presumed Letterer-Siwe disease, the acute
      multiorgan variant, have been reported in twins and siblings. Only recently has
      the Histiocyte Society established a criterion for a "definitive diagnosis" of
      Langerhans cell histiocytosis--the presence of Birbeck granules within the cells
      of the histiocytic infiltrate. We report the fatal outcome of Langerhans cell
      histiocytosis in monozygotic twin infants. There is no satisfactory explanation
      why Langerhans cell histiocytosis occurs concurrently in twins. We suggest that
      cytokines may provide an endogenous signal that triggers the pathologic
      proliferation of Langerhans cells.

PMID- 1999527
TI  - Allergic contact dermatitis to two antioxidants in latex gloves: 4,4'-thiobis(6
      tert-butyl-meta-cresol) (Lowinox 44S36) and butylhydroxyanisole. Allergen
      alternatives for glove-allergic patients.
AB  - Allergic contact dermatitis developed on the hands and/or face of two patients
      after exposure to latex examination gloves. Both patients were patch test
      negative to the usual rubber allergens, but both had a positive patch test
      reaction to 4,4'-thiobis(6-tert-butyl-m-cresol) (Lowinox 44S36). Patient 2 was
      also patch test positive to butylhydroxyanisole. The patients were tested with
      other gloves, to find gloves that they could safely use. Glove manufacturers were
      queried to ascertain the occurrence of Lowinox 44S36 and butylhydroxyanisole in
      different brands of latex and vinyl examination gloves. A list of gloves and
      their associated allergens was generated and is provided to assist dermatologists
      in helping patients choose gloves free of specific allergens.

PMID- 1999528
TI  - Pathogenesis of onychoschizia (lamellar dystrophy).
AB  - Onychoschizia or lamellar dystrophy of the nails is common, especially in adult
      women, but little information is available about its cause. Most theories involve
      environmental factors, but supportive experimental data are scarce. Therefore we
      studied the in vitro nail changes produced by several organic solvents,
      detergents, water, other polar materials, and both acidic and basic solutions.
      Challenged and control fingernail clippings were examined grossly,
      microscopically, and by scanning electron microscopy at regular intervals. There
      was a progressive increase in severity with prolonged wetting and drying. By 3
      weeks, scanning electron microscopy demonstrated unattached individual cells in
      empty spaces in which separation was more prominent. Basic solutions caused some
      softening, but layering (peeling) was seen only after repeated hydration and
      dehydration. Although other factors may influence onychoschizia, the typical
      changes can be produced in normal nails after a 21-day challenge of repeated
      exposure to water followed by dehydration. These findings suggest a probable
      cause for the condition and a logical approach to management.

PMID- 1999529
TI  - Isotretinoin for refractory lupus erythematosus.
AB  - We describe six patients with cutaneous manifestations of lupus erythematosus who
      were treated with isotretinoin, 1 mg/kg/day. In each case the cutaneous lesions
      had proved resistant to systemic corticosteroids and antimalarial therapy.
      Treatment with isotretinoin resulted in rapid clinical improvement in all cases.
      Recurrences were similarly rapid when the drug was discontinued. Side effects
      were minimal and easily controlled by adjustments in dose or by the use of
      lubricants.

PMID- 1999530
TI  - Unfading acral microlivedo. A discrete marker of thrombotic skin disease
      associated with antiphospholipid antibody syndrome.
AB  - Small erythematous or cyanotic lesions on the hands and feet of four patients
      with antiphospholipid antibodies are described. These discrete lesions outline
      capillaries and do not disappear when pressure is applied. The histologic
      features are identical to those described in skin thrombotic syndrome associated
      with antiphospholipid antibodies, that is, microthrombi in dermal vessels without
      inflammation. In addition to indicating antiphospholipid antibodies in apparently
      healthy patients, this sign could be a marker of risk for large-vessel
      thrombosis.

PMID- 1999531
TI  - Cutaneous manifestations in patients with essential thrombocythemia.
AB  - In a retrospective study of 268 patients with essential thrombocythemia, related
      cutaneous manifestations were found in 58 (22%). In 27 cases (10%) the related
      skin lesions were present at the time of the primary diagnosis of essential
      thrombocythemia. Hematomas, ecchymoses, petechiae, or purpura occurred in 24
      (41%) of the 58 patients. Fifteen patients (26%) had erythromelalgia, in 11 of
      whom it was the initial complaint. Livedo reticularis, recurrent superficial
      thrombophlebitis, ischemic complications with gangrene, leg ulcers, or ulcers on
      the toes were other manifestations. Urticaria occurred in two patients, and
      Raynaud's phenomenon and necrotizing vasculitis were each observed in one
      patient. Platelet function may be abnormal, and this was found in 13 of 19
      patients studied, 9 of whom had spontaneous platelet aggregation. Knowledge of
      the cutaneous manifestations in essential thrombocythemia may lead to its earlier
      detection. Prompt diagnosis of essential thrombocythemia is important because
      treatment may prevent severe hemorrhagic or thrombotic events.

PMID- 1999532
TI  - Allergy and toxicodermia from shiitake mushrooms.
AB  - Skin and respiratory symptoms developed within 2 months of exposure in a patient
      involved in the commercial production of shiitake mushrooms. A diagnosis of
      contact urticaria and allergic contact dermatitis from shiitake mushrooms was
      confirmed by prick and patch tests. The respiratory symptoms, their timing, the
      presence of precipitating IgG antibodies to shiitake spores and increased amounts
      of inflammatory cells and T lymphocytes in bronchoalveolar lavage indicated
      allergic alveolitis (mushroom worker's disease). A generalized exanthem developed
      in a second patient after eating raw shiitake mushrooms. Reactions to prick and
      patch tests with shiitake mushrooms were negative. The skin eruption in this
      patient corresponded to the previously reported shiitake-induced toxicodermia.

PMID- 1999533
TI  - Round fingerpad sign: an early sign of scleroderma.
AB  - We describe a clinical skin sign in scleroderma termed round fingerpad sign. This
      term refers to disappearance of the peaked contour on fingerpads and replacement
      with a hemisphere-like fingertip contour; this change is especially apparent on
      the ring fingers. A positive round fingerpad sign was found in 72 of 72 ring
      fingers in 36 patients with progressive systemic sclerosis in 69 of 72 ring
      fingers in patients with mixed connective tissue disease, and in 24 of 24 ring
      fingers of patients with Raynaud's phenomenon and sclerodactyly. In contrast, a
      negative round fingerpad sign was seen in 240 of 240 fingers in normal women
      (controls). The high sensitivity of this sign is noteworthy. A positive round
      fingerpad was seen in sign not only typical scleroderma patients but also in
      groups with less severe skin sclerosis (i.e., in those patients with mixed
      connective tissue disease or those with Raynaud's phenomenon and sclerodactyly).
      The sign is a new and useful clinical marker for the early diagnosis of
      scleroderma.

PMID- 1999534
TI  - Immune sensitization against epidermal antigens in polymorphous light eruption.
AB  - To get further insight into the pathogenesis of polymorphous light eruption, we
      studied nine patients with polymorphous light eruption and six healthy persons.
      Two skin biopsy specimens were obtained from each person, one from previously
      ultraviolet light-irradiated skin and another one from unirradiated skin. An
      epidermal cell suspension, skin homogenate, or both were prepared from each
      specimen. Autologous cultures were made with peripheral blood mononuclear cells
      combined with irradiated or unirradiated skin homogenate and peripheral blood
      mononuclear cells combined with irradiated or unirradiated epidermal cell
      suspension. Cell proliferation was assessed by 3H-thymidine incorporation assay.
      The response of peripheral blood mononuclear cells to unirradiated epidermal
      cells or unirradiated skin homogenate was similar in both patients and controls.
      However, peripheral blood mononuclear cells from patients with polymorphous light
      eruption showed a significantly increased proliferative response to both
      irradiated epidermal cells and irradiated skin homogenate. Our results indicate
      that ultraviolet light increases the stimulatory capability of polymorphous light
      eruption epidermal cells in a unidirectional mixed culture with autologous
      peripheral blood mononuclear cells. This suggests that an immune sensitization
      against autologous ultraviolet light-modified skin antigens occurs in
      polymorphous light eruption.

PMID- 1999535
TI  - Lobulated intradermal nevus. Report of three cases.
AB  - We report the cases of three patients with lobulated intradermal nevi. Biopsy
      specimens showed similar findings, that is, fatty infiltration within nests of
      nevus cells, neuroid differentiation of nevus cells, and dermal fibrosis. Our
      cases probably represent an unusual form of regressing melanocytic nevus.

PMID- 1999536
TI  - Grafting of venous leg ulcers. An intraindividual comparison between cultured
      skin equivalents and full-thickness skin punch grafts.
AB  - Skin equivalents that consisted of a noncontracted collagen gel populated with
      allogeneic fibroblasts and covered with autologous cultured keratinocytes were
      used for grafting venous leg ulcers. The results were compared in the same
      patient with those obtained with a routinely used standard method of grafting
      with autologous full-thickness punch grafts. The skin equivalents and the punch
      grafts were grafted successfully in four of five patients. The median healing
      time of ulcers grafted with skin equivalents was 18 days whereas that of ulcers
      covered with punch grafts was 15 days. The cosmetic appearance of the skin
      equivalent-grafted ulcers was better than that of the punch-grafted ulcers.

PMID- 1999537
TI  - Treatment of pyoderma gangrenosum with cyclosporine: results in seven patients.
AB  - The mainstay of therapy for pyoderma gangrenosum has been corticosteroids, but
      many patients respond poorly. During the past 2 years we have treated seven
      patients who had pyoderma gangrenosum with cyclosporine after their condition
      proved resistant to conventional therapy. No evidence of permanent toxicity from
      cyclosporine was detected and treatment with other immunosuppressive agents was
      discontinued in five of seven cases. Tuberculosis was reactivated in one patient.
      Three patients had a remission, three had an intermediate response, and one did
      not respond. These results indicate that cyclosporine is useful in the treatment
      of patients with refractory pyoderma gangrenosum and suggest an immune mechanism
      in the pathogenesis of this disorder.

PMID- 1999538
TI  - Propylene glycol dermatitis.
AB  - Propylene glycol is a commonly used vehicle for topical preparations. Although it
      is well suited for this purpose, it is capable of producing both primary irritant
      skin reactions and allergic sensitization. The literature on propylene glycol is
      reviewed, with particular attention to the nature of these adverse cutaneous
      effects. Guidelines for patients sensitive to propylene glycol are discussed.

PMID- 1999539
TI  - Porokeratoses: immunohistochemical, light and electron microscopic evaluation.
AB  - Punch biopsy specimens of 14 patients with porokeratosis of Mibelli (n = 1),
      disseminated superficial porokeratosis (n = 6), disseminated superficial actinic
      porokeratosis (n = 4), porokeratosis plantaris, palmaris et disseminata (n = 2),
      and punctate porokeratosis (n = 1) were obtained for light and electron
      microscopy for evaluation of possible differences between these clinical
      variants. Langerhans cells in close contact with early degenerating keratinocytes
      could be observed in the epidermis. To study the cellular composition of the
      epidermal inflammatory infiltrate immunohistochemistry was performed. These
      studies demonstrated that the predominant cell type in these infiltrates are
      helper T cells, intermingled with Leu-6+ Langerhans cells. Despite the clinical
      variation and possible different etiologic or triggering mechanisms, the
      immunohistochemical and morphologic changes in all types of porokeratosis are the
      same and seem to represent a uniform reaction pattern.

PMID- 1999540
TI  - Pyoderma gangrenosum followed by subcorneal pustular dermatosis in a patient with
      IgA paraproteinemia.
AB  - Six months after the occurrence of pyoderma gangrenosum, subcorneal pustular
      dermatosis developed in a 60-year-old woman. The patient's serum was found to
      contain an IgA-lambda paraprotein. Although similar cases have been reported,
      this case is unique in that a distinct episode of pyoderma gangrenosum was
      followed by subcorneal pustular dermatosis.

PMID- 1999541
TI  - Rhodococcus infection of the skin with lymphadenitis in a nonimmunocompromised
      girl.
AB  - A 7-year-old girl had a 4 X 3 X 3 cm nodule on the left wrist with axillary
      lymphadenopathy. Acid-fast bacilli were seen on a smear from a biopsy specimen of
      this granulomatous skin lesion. A Rhodococcus species grew on culture. Skin
      infections caused by Rhodococcus may be more common than the few prior case
      reports suggest.

PMID- 1999542
TI  - Persistent light reaction to hexachlorophene.
AB  - The first patient with what appears to be persistent light reaction caused by
      hexachlorophene alone is reported. Persistent light reaction may occur in
      patients with milder degrees of photosensitivity, and appropriate photopatch
      testing should be performed.

PMID- 1999543
TI  - Late metastases of cutaneous melanoma: case report and literature review.
AB  - The development of delayed metastases, although rare, is well documented in
      patients with invasive cutaneous melanoma. Only 24 cases, including ours, are
      clearly documented in the literature. We describe a 56-year-old woman who had an
      acral lentiginous melanoma of the right hand (thickness 1.2 mm). Thirteen years
      after excision and postoperative irradiation, a subcutaneous metastasis developed
      in the right arm. One year later the patient died with disseminated bone
      metastases. This case, as with most of those with delayed metastases, has typical
      features: female sex; location at a site other than the back, arm, neck, or
      scalp; and primary tumor thickness between 1.2 and 2.5 mm.

PMID- 1999544
TI  - Hereditary lactate dehydrogenase M-subunit deficiency: lactate dehydrogenase
      activity in skin lesions and in hair follicles.
AB  - A 16-year-old Japanese girl had desquamating erythematosquamous lesions mostly on
      the extensor surface of the extremities. The lesions were worse in summer. The
      patient also had a mild muscle pain after strenuous exercise. Her paternal and
      maternal grandfathers are cousins. An analysis of lactic acid dehydrogenase (LDH)
      isozymes in her serum revealed a single peak of LDH1. Analysis of LDH isozymes of
      erythrocytes demonstrated a complete lack of LDH M-subunit in the patient and a
      substantial lack in the parents. The epidermis of the diseased skin and scalp
      hair follicles of the patient were virtually devoid of LDH activity.

PMID- 1999546
TI  - A syndrome characterized by nodular eosinophilic infiltration of the skin and
      immunoglobulin isotype imbalance.
AB  - A 9-year-old boy had recurrent acute, plaquelike, nodular infiltrations with
      overlying vesicles and bullae of the face and right hand. Histologically, the
      lesions consisted of a perivascular and periadnexal lymphohistiocytic infiltrate
      with many eosinophils. The lesions responded to dapsone therapy. Laboratory
      studies revealed blood eosinophilia, hyperimmunoglobulinemias E and G4, and
      hypoimmunoglobulinemias M and G1-3, which normalized after treatment. The
      patient's immune deviation is consistent with a transient imbalance of lymphokine
      production in helper T cells.

PMID- 1999545
TI  - Thrombotic vasculopathy associated with cryofibrinogenemia.
AB  - Cryofibrinogenemia refers to the presence of cold-precipitable plasma proteins
      associated with a variety of disorders, including malignancies, inflammatory
      processes, and thrombohemorrhagic phenomena. Few cases of essential or primary
      cryofibrinogenemia are reported. We report a case in a 48-year-old man of
      essential cryofibrinogenemia and hemorrhagic necrosis of the ears and of the
      upper and lower extremities. Histopathologic studies demonstrated extensive
      eosinophilic thrombi in the dermal vasculature, with minimal inflammation and no
      vasculitis. Cryofibrinogenemia should be considered in the investigation of
      patients with otherwise unexplained cold intolerance and dermal thrombosis
      associated with minimal or no inflammation.

PMID- 1999547
TI  - Trichothiodystrophy with chronic neutropenia and mild mental retardation.
AB  - Trichothiodystrophy is a feature of several diseases that consist of
      characteristic hair shaft abnormalities and a wide spectrum of other
      developmental defects. Detection of sulfur-deficient hairs identifies this
      disorder and separates it from other similar ectodermal dysplasias with normal
      sulfur content. Detection of low sulfur hair syndrome is also important for
      genetic counseling, because the disease appears to be an autosomal recessive
      trait. We report a patient with chronic neutropenia, mild mental retardation, and
      low sulfur content in hair. Our case expands the spectrum of disorders associated
      with trichothiodystrophy.

PMID- 1999548
TI  - Multiple granular cell tumors associated with giant speckled lentiginous nevus
      and nevus flammeus in a child.
AB  - We describe an 11-year-old girl in whom multiple cutaneous granular cell tumors
      were associated with a giant speckled lentiginous nevus and an extensive nevus
      flammeus. An association between granular cell tumors and pigmented skin lesions
      has been reported twice previously and supports a neural origin for these tumors.
      An abnormality of neural crest development is proposed to explain the coexistence
      of three uncommon and unusually extensive cutaneous disorders in this patient.
      This case may represent a further variant of phakomatosis pigmentovascularis.

PMID- 1999549
TI  - Group A streptococcal cellulitis-adenitis in a patient with acquired
      immunodeficiency syndrome.
AB  - A rapidly enlarging left inguinal adenitis, with positive groove sign, and fever,
      chills, malaise, hypotension, headache, scarlatiniform rash, choleroid diarrhea,
      and proteinuria developed in an homosexual man who was positive for human
      immunodeficiency virus. The needle aspiration of the inguinal mass showed group A
      beta-hemolytic streptococci and the blood cultures were negative, suggesting
      group A streptococcal cellulitis-adenitis with toxic strep syndrome. Treatment
      with penicillin and surgical drainage was successful. Bacterial infections
      associated with defective humoral immunity appear to be common in patients with
      acquired immunodeficiency syndrome (AIDS), and some of these infections have a
      remarkable extensive and lethal evolution. Therefore streptococcal adenitis
      should be considered in any patient with AIDS or AIDS-related syndrome in whom
      rapidly enlarging inguinal nodes develop.

PMID- 1999550
TI  - Xeroderma pigmentosum lesions related to ultraviolet transmittance by clothes.
AB  - Xeroderma pigmentosum is associated with severe actinic degeneration of the skin.
      Our patient with xeroderma pigmentosum showed increasing actinic damage in some
      areas covered by clothes. We therefore performed a complete evaluation of the
      patient's exposure to ultraviolet radiation. This included transmission
      measurements of the patient's clothes, glasses, and car windows. The transmission
      of UVB (280 to 320 nm) by the clothes varied from none to 17.8%. The transmitted
      UVB radiation was proportional to the clinical manifestations of xeroderma
      pigmentosum. The patient's wardrobe was changed, and UVA-blocking film was
      applied to the windows of the car and house. A decline in manifestations was seen
      after 18 months of improved ultraviolet protection.

PMID- 1999551
TI  - Abnormal epidermal changes after argon laser treatment.
AB  - A 26-year-old woman with a congenital port-wine stain on the forehead was treated
      three times at 2-month intervals with an argon laser. Six months after the last
      treatment, moderate blanching and mild scaling confined to the treated area was
      observed. A biopsy specimen of the treated area revealed a significant decrease
      in ectatic vessels. However, epidermal changes similar to those of actinic
      keratosis with disorganized cell layers and marked cytologic abnormalities were
      seen. Analysis of peripheral blood lymphocytes for a defect in DNA repair was
      negative. Multiple, argon laser-induced photothermal effects may be responsible
      for the changes observed in our case and may lead to premalignant epidermal
      transformation.

PMID- 1999552
TI  - Hereditary deficiency of C5 in association with discoid lupus erythematosus.
AB  - A 29-year-old woman with discoid lupus erythematosus had undetectable classic
      pathway complement activity. Hypocomplementemia was due to selective deficiency
      of C5. One of her children was also deficient. To our knowledge this is the first
      documented case of an association between discoid lupus erythematosus and C5
      deficiency.

PMID- 1999553
TI  - Immunoglobulin isotypes in human minor gland saliva.
AB  - Lower labial, upper labial, palatine (minor), and parotid (major) gland saliva
      samples from 18 young adult males were quantitatively assayed for the presence of
      IgA1, IgA2, IgM, and IgG. The mean (+/- standard deviation) concentrations of IgA
      (sum of IgA1 + IgA2) were 79 +/- 42 micrograms/mL (parotid), 111 +/- 42
      micrograms/mL (lower labial), 69 +/- 72 micrograms/mL (upper labial), and 88 +/-
      68 micrograms/mL (palatine). Total IgA concentrations were positively correlated
      among different minor-gland samples from the same subject, although these
      correlations did not reach significance. Upper-labial-gland saliva samples
      contained significantly (at least p less than 0.05) lower concentrations of IgA1
      than those found in parotid or lower-labial minor-gland secretions. All three
      minor-gland sources of saliva contained significantly (p less than 0.002) higher
      levels of IgG than did parotid saliva. Upper-labial fluids had significantly (p
      less than 0.02) higher IgG concentrations than lower-labial saliva. IgM could be
      detected in 89% of parotid saliva samples and 75% of the palatine saliva samples.
      Palatine IgM concentrations (8.2 +/- 17.8 micrograms/mL) were significantly (p
      less than 0.05) higher than parotid IgM concentrations (0.6 +/- 0.4
      micrograms/mL). IgM was detected much less frequently and at lower concentrations
      in lower- and upper-labial-gland saliva. These data reveal that minor-gland
      saliva from different oral sites may contain distinctive immunoglobulin isotype
      patterns, and expressions of host defense may vary within each micro-environment.

PMID- 1999554
TI  - Human dentin-matrix-derived bone morphogenetic protein.
AB  - Bone morphogenetic protein (BMP) was extracted from human dentin matrix with 4
      mol/L guanidine-HCl and was purified by liquid chromatography. SDS-PAGE and IEF
      showed that the purified BMP was homogeneous and induced new bone formation in
      situ after three weeks when implanted into muscle pouches in Wistar rats. The
      molecular weight of BMP was estimated to be about 20.0 kDa by SDS-PAGE, and the
      pI value was 8.8 by IEF. Amino acid analysis suggested that BMP is a protein
      containing 191 amino acids. A partial amino acid sequence was obtained from the
      final purified BMP. Dentin-matrix-derived BMP is probably not identical to, but
      is similar to, bone-matrix-derived BMP, though both types of BMP have the same
      action in vivo.

PMID- 1999555
TI  - Alkaline phosphatase induces the deposition of calcified layers in relation to
      dentin: an in vitro study to mimic the formation of afibrillar acellular
      cementum.
AB  - An attempt was made to test the hypothesis that alkaline phosphatase, an enzyme
      which is abundant in periodontal ligament, plays a role in the formation of
      acellular root cementum. Thin slices of bovine dentin were incubated in Iscove
      Modified Dulbecco's Medium supplemented with 10% normal rabbit serum and 10
      mmol/L beta-glycerophosphate (beta-GP) or folded into pericardial explants.
      Intestinal bovine alkaline phosphatase (APase), covalently linked to agarose
      beads, was added to the cultures. In the presence of the enzyme, the dentin
      slices were covered with thin layers of mineralized material. Such layers were
      not observed in cultures not provided with APase-beads or beta-GP. They also did
      not form in relation to demineralized dentin. The layers of calcified material
      appeared to consist of crystallites embedded in a granular matrix of moderate
      electron density, which often exhibited the presence of incremental lines and
      resembled the matrix of afibrillar acellular cementum formed under in vivo
      conditions. When pericardial explants were interposed between the enzyme
      containing beads and the dentin, mineral deposition in relation to the dentin was
      retarded. This finding lends support to the view that soft connective tissues
      interfere with the free diffusion of phosphate.

PMID- 1999556
TI  - Acid profile in carious dentin.
AB  - Organic acids in carious dentin from 69 permanent teeth were analyzed by gas
      chromatography. Lactate, acetate, propionate, and butyrate were detected in most
      samples, and limited amounts of isobutyrate, valerate, isovalerate, caproate, and
      isocaproate were occasionally detected. Lactate, acetate, and propionate were
      major acids and altogether accounted for about 90% of total acid in most samples
      of carious dentin. However, the proportion of these three acids varied among the
      samples. Some samples contained over 85% lactate, while others contained mainly
      acetate and propionate. A high percentage of acetate was usually accompanied by
      an appreciable amount of propionate. All seven samples in carious dentin under
      fillings or restorations had little lactate, but a high percentage of acetate
      plus propionate. The differences in acid profiles of carious dentin may reflect
      differences in the microbial ecology of carious dentin, and a stage of progress
      of dentin caries or a type of dentin caries.

PMID- 1999557
TI  - The distribution of magnesium in developing rat incisor dentin.
AB  - Previous studies have shown that rat incisor dentin contains a considerable
      amount of magnesium that is distributed heterogeneously. The cementum-related
      dentin, especially its incisal portion, is richest in magnesium. It was the
      purpose of the present study to investigate the changes that occur in the
      magnesium content during dentin maturation. Cross-sections were prepared from rat
      incisors at the apical, middle, and incisal levels. By means of an electron
      microprobe, tracings were made of the Ca-, Mg-, and P- signal frequencies.
      Comparison of corresponding dentin layers within and between the cross-sections
      showed that the Mg/P molar ratio was always higher in the cementum-related dentin
      (CRD) than in the enamel-related dentin (ERD) and increased from the apex toward
      the incisal edge. Especially in the incisal cross-section, an increase in Mg/P
      was found from the older (peripheral) toward the younger (central) dentin layers.
      As the Mg/P ratio varied from 0.07 to 0.33, the Ca/P ratio was found to fluctuate
      from 1.48 to 1.15. The two ratios appeared to be highly correlated (r = -0.97; p
      less than 0.001), suggesting that Mg replaces Ca and is bound to phosphate.

PMID- 1999558
TI  - An experimental study in dogs of transseptal fiber arrangement between teeth
      which have emerged in rotated or non-rotated positions.
AB  - Transseptal fibers of the periodontal ligament are thought to play a role in
      relapse after orthodontic derotation. The aim of this study was to compare the
      location of the attachment site and the arrangement of the transseptal fibers in
      rotated emerged and non-rotated emerged teeth. In five dogs, unilaterally, the
      first upper premolars were replaced into a rotated position, before emergence.
      Histological evaluation showed that transseptal fibers developed in the
      experimental as well as in the control specimens. In all cases, transseptal
      fibers bridged the shortest distance between two adjacent teeth. It was concluded
      that the attachment site of the transseptal fibers was not determined by the
      tooth anatomy itself, but by the tooth position and its orientation in the dental
      arch during transseptal fiber development.

PMID- 1999559
TI  - Correlates of dental anxiety among older adults.
AB  - This paper reports on a study of dental anxiety among adults aged 50 years and
      over living independently in two communities in Ontario, Canada. Subjects were
      identified by means of a telephone survey based on random-digit dialing. Data on
      dental anxiety were collected from 580 subjects by means of a self-completed
      questionnaire and were measured by the Dental Anxiety Scale (DAS) (Corah, 1969).
      The mean DAS score was 7.8, and 8.4% of subjects were classified as dentally
      anxious. Age was the only demographic factor associated with dental anxiety.
      Older individuals had lower DAS scores than younger individuals (p less than
      0.0001). There was also a significant association between dental anxiety and
      general fearfulness measured by the Fear Survey Schedule II (Geer, 1965) (r =
      0.31; p less than 0.001). A series of regression analyses revealed that dental
      anxiety was a significant predictor of a number of behavioral and oral health
      outcomes. While these results confirm that dental anxiety is less prevalent among
      older adults than in younger populations, it has a number of important
      consequences with respect to dental care provision.

PMID- 1999560
TI  - A new approach to the study of tooth wear.
AB  - Human tooth wear occurs so slowly that traditionally it has needed months or
      years to be measurable. This study showed that microscopic changes in wear
      patterns on human teeth could be detected in a matter of days and could be used
      as indicators of rates of wear. Thus, daily or weekly changes in rates of wear
      can be documented for specific locations on teeth. For instance, through this new
      approach, rates of wear of human teeth were shown to be significantly slower than
      rates of wear of the teeth of laboratory monkeys raised on hard or soft diets.
      Similar techniques may ultimately be used to monitor subtle changes in tooth use-
      including those associated with growth and development and those occurring in
      response to various dental clinical procedures.

PMID- 1999561
TI  - Dentin-bonding molar efficiency using N-phenylglycine, N-phenyl-beta-alanine, or
      N-methyl-N-phenylglycine.
AB  - Three structurally related substituted amino acids (N-compounds) were studied in
      a three-step dentin-bonding protocol. The first step of an acidic ferric oxalate
      solution and the third step of a surface-active comonomer were held constant
      throughout the study. In the second step, the amount of the N-compound--either N
      phenylglycine (NPG), N-methyl-N-phenylglycine (NMNPG), or N-phenyl-beta-alanine
      (NPBA)--was varied in acetone from 0 mol/L through 5 x 10(-1) mol/L in seven
      steps. At 1 x 10(-3) mol/L for NPG and NMNPG, average bond strength values were
      7.4 +/- 2.2 and 10.5 +/- 2.7 MPa. The highest bond strength value for NMNPG was
      at 1 x 10(-2) mol/L, with 13.2 +/- 4.0 MPa. The highest value for NPG was at 1 x
      10(-1) mol/L, with a value of 11.8 +/- 2.5 MPa. The average bond strength for
      NPBA did not differ from zero across the entire range of concentrations. Molar
      efficiency was defined as the bond strength per mole of these applied N
      compounds. For the two N-compounds that did provide adhesion to dentin, NPG and
      NMNPG, the average bond strengths rose, peaked, and fell as the amounts of
      applied N-compound were increased. The molar efficiency dropped off as the
      concentration of applied N-compound rose. The least operator-sensitive and most
      efficient N-compound, NMNPG, delivered a bond strength equivalent to that of NPG,
      with 10% of the applied NPG amount.

PMID- 1999562
TI  - Abrasion of human enamel by different dental ceramics in vitro.
AB  - Manufacturers generally quote indentation hardness values when predicting the
      clinical wear potential of newly introduced ceramic restoratives. The objective
      of this study was to determine whether in vitro two-body wear correlated well
      with hardness. A modified polisher was used to abrade enamel cylinders against
      polished disks of commercially available dental porcelains and glass. Enamel loss
      after four h was measured with a micrometer. Five ceramic materials were tested,
      and enamel abrasion rates were correlated with Knoop hardness values. Dicor and
      Dicor coated with a shading porcelain were found to cause the lowest wear of
      enamel. These rates were statistically significantly lower than those obtained
      with Optec, the most abrasive material. These findings may be due to
      microstructural differences between the materials. Knoop hardness showed poor
      correlation with the results of the abrasive testing.

PMID- 1999563
TI  - Daily dose estimates of mercury from dental amalgams.

PMID- 1999564
TI  - Special report: dental amalgam.

PMID- 1999565
TI  - What to do about dry mouth.

PMID- 1999567
TI  - Treating a patient with palatal Kaposi's sarcoma.

PMID- 1999566
TI  - Combining endodontic, periodontic and restorative treatments.

PMID- 1999568
TI  - Picking a computer. Tips on finding the right system for you.

PMID- 1999569
TI  - Am I willing to advance?

PMID- 1999570
TI  - Code on Dental Procedures and Nomenclature. Report from the Council on Dental
      Care programs.

PMID- 1999571
TI  - Temporarily permanent.

PMID- 1999573
TI  - Dental team earnings. Hygienists, assistant salaries rise.

PMID- 1999572
TI  - Dental implants.

PMID- 1999574
TI  - Measuring dental fees. Route to a truer picture.

PMID- 1999575
TI  - ADA sues HHS over data bank.

PMID- 1999576
TI  - Rules & regs: who needs them?

PMID- 1999577
TI  - Update on implants.

PMID- 1999579
TI  - Hemorrhage after endosseous implant.

PMID- 1999578
TI  - Input on implants.

PMID- 1999580
TI  - Periodontics.

PMID- 1999581
TI  - Government reports oral cancer deaths.

PMID- 1999582
TI  - Implants used successfully in atrophied lower jaws.

PMID- 1999583
TI  - Implant use grows, courses multiply.

PMID- 1999584
TI  - Senator Edward Kennedy talks about health care.

PMID- 1999585
TI  - Lasers in dentistry.

PMID- 1999586
TI  - Diagnosing periodontal disease. New tools to solve an old problem.

PMID- 1999588
TI  - Relieving patient anxiety. A new approach.

PMID- 1999587
TI  - Short term changes a surprise with smokeless tobacco. Oral lesions.

PMID- 1999590
TI  - Does the laser work on hard dental tissue?

PMID- 1999589
TI  - Denture adhesives. Choosing the right powders and pastes.

PMID- 1999591
TI  - Have porcelain veneers arrived?

PMID- 1999592
TI  - The cocaine connection. Users imperil their gingiva.

PMID- 1999593
TI  - Unusual allergic reaction follows allergy testing.

PMID- 1999595
TI  - How patients benefit from surgical-orthodontic care.

PMID- 1999594
TI  - What's the diagnosis when facial swelling and paralysis develop?

PMID- 1999597
TI  - Florida woman with AIDS virus sues dental plan.

PMID- 1999596
TI  - Response to '60 Minutes'.

PMID- 1999598
TI  - Anesthesia: who regulates what?

PMID- 1999600
TI  - Ethics and rationing health care.

PMID- 1999599
TI  - The use of dishwashers for sterilization.

PMID- 1999601
TI  - Florida dentist linked to two more HIV cases.

PMID- 1999602
TI  - Are you willing to treat AIDS patients?

PMID- 1999603
TI  - Dr. Ronald E. Goldstein talks about esthetic care. Interview by Lawrence Meskin.

PMID- 1999604
TI  - Excess capacity in dentistry or a shortage?

PMID- 1999605
TI  - Nitrous oxide and its abuse.

PMID- 1999606
TI  - Reviewing vital bleaching and chemical alterations.

PMID- 1999608
TI  - The multidisciplinary approach managing enamel defects.

PMID- 1999607
TI  - What are the risk factors of osteoporosis? Assessing bone health.

PMID- 1999610
TI  - Bonding resin to dentin. Fact or fantasy?

PMID- 1999609
TI  - Preventing dry socket. A simple procedure that works.

PMID- 1999611
TI  - An approach to dealing with mucosal damage.

PMID- 1999612
TI  - Using heat to assess pulp inflammation.

PMID- 1999613
TI  - Occlusions altered by removable appliances.

PMID- 1999614
TI  - Interim policy on HIV-infected dentists.

PMID- 1999616
TI  - Selecting computer hardware to get the right system, ask the right questions.

PMID- 1999615
TI  - Evolving primary pulp therapy techniques.

PMID- 1999617
TI  - Coping with the recession.

PMID- 1999618
TI  - Perioperative myocardial ischemia in patients undergoing noncardiac surgery--I:
      Incidence and severity during the 4 day perioperative period. The Study of
      Perioperative Ischemia (SPI) Research Group.
AB  - To determine the incidence and characteristics of perioperative myocardial
      ischemia, the electrocardiographic (ECG) changes consistent with ischemia during
      the 4 day perioperative period were documented and characterized in 100 patients
      with or at risk for coronary artery disease undergoing noncardiac surgery. Using
      continuous two channel ECG monitoring (leads CC5 and CM5), the frequency and
      severity of ECG ischemic episodes defined by ST segment depression greater than
      or equal to 1 mm or elevation greater than or equal to 2 mm during the
      preoperative (up to 2 days), intraoperative and early postoperative (first 2
      days) periods were compared. Preoperatively, 28 patients (28%) exhibited 105
      episodes of ischemia; intraoperatively, 27 patients exhibited 39 episodes and
      postoperatively, 42 patients exhibited 187 episodes. There was no difference
      between the pre- and intraoperative episode characteristics. However,
      postoperative ischemic episodes were the most severe. The mean ST change was 1.5,
      2 and 2.6 mm for pre-, intra- and postoperative episodes, respectively (p less
      than 0.0001 postoperative versus pre- or intraoperative); duration of ischemic
      episodes was 69, 45 and 207 min, respectively (p less than 0.005 postoperative
      versus preoperative, p less than 0.001 versus intraoperative) and area under the
      ST curve was 88, 74 and 383 mm.min (p less than 0.009 postoperative versus
      preoperative, p less than 0.005 versus intraoperative). Ninety-four percent of
      all postoperative ischemic episodes were silent; 80% of all episodes occurred
      without acute change (+/- 20% of control) in heart rate and 77% of intraoperative
      episodes occurred without acute change in blood pressure.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1999619
TI  - Perioperative myocardial ischemia in patients undergoing noncardiac surgery--II:
      Incidence and severity during the 1st week after surgery. The Study of
      Perioperative Ischemia (SPI) Research Group.
AB  - Because of the importance of postoperative myocardial ischemia and because
      substantial physiologic changes can occur for prolonged periods postoperatively,
      the incidence, severity and temporal course of myocardial ischemia were studied
      in 100 high risk patients during the 1st week after major noncardiac surgery.
      Electrocardiographic (ECG) changes consistent with ischemia were continuously
      monitored using ambulatory solid state ECG in the 100 patients with or at risk
      for coronary artery disease. Ischemic episodes were defined as reversible ST
      segment depression greater than or equal to 1 mm or elevation greater than or
      equal to 2 mm above the baseline value, with the baseline adjusted for
      respiratory and positional variation and temporal drift. All ischemic episodes
      were confirmed by three independent blinded investigators using hard-copy
      recordings. Total ECG monitoring time was 10,445 h. Twenty-seven patients (27%)
      developed 437 episodes of ischemia during the 1st week after surgery. The total
      duration of ischemia was 18,658 min, or 1.8 min of ischemia/h monitored. Ischemia
      was most severe during the early (days 0 to 3) versus late (days 4 to 7)
      postoperative period: 284 versus 153 episodes; 2.2 versus 1.2 min of ischemia/h.
      The greatest severity occurred on postoperative day 3: 109 episodes, 3.4 min of
      ischemia/h monitored, 1.5 mm mean ST change and 130 min mean duration. However,
      in 8% of patients, severe episodes also occurred late: postoperative day 6 = 44
      episodes, 1.7 min of ischemia/h monitored, 1.3 mm mean ST change (59% greater
      than or equal to 2 mm) and 92 min mean duration. Most ischemic episodes (57%)
      were associated with tachycardia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1999620
TI  - Influence of right bundle branch block on short- and long-term survival after
      acute anterior myocardial infarction.
AB  - The impact of right bundle branch block on long-term prognosis after anterior
      wall myocardial infarction is unclear. In 932 patients with Q wave anterior
      infarction, the short- and long-term prognostic significance of the presence of
      right bundle branch block was analyzed. Compared with 754 patients without block,
      178 patients with right bundle branch block after myocardial infarction showed an
      increased incidence of left ventricular failure (72% versus 52%, p less than
      0.001) and increased in-hospital (32% versus 8%, p less than 0.001) and 1 year
      after hospital discharge (17% versus 7%, p less than 0.001) cardiac mortality
      rates. The presence of right bundle branch block was an independent predictor of
      increased in-hospital and 1-year mortality when entered in a multivariate
      analysis. However, the absence of left ventricular failure identified a subgroup
      of patients with right bundle branch block with low in-hospital (4%) and 1 year
      postdischarge (5%) cardiac mortality rates comparable with those of patients with
      neither failure nor right bundle branch block (1.7% and 4.8%, respectively). In
      the presence of left ventricular failure, patients with associated right bundle
      branch block had higher in-hospital (43% versus 14%, p less than 0.01) and 1 year
      postdischarge (24% versus 9%, p less than 0.01) cardiac mortality rates than
      those of patients with failure but no right bundle branch block. Thus, the
      presence of right bundle branch block after anterior myocardial infarction is an
      independent marker of poor prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1999621
TI  - Right bundle branch block after anterior myocardial infarction.

PMID- 1999622
TI  - Thrombosis-related markers in unstable angina pectoris.
AB  - While thrombus formation has been implicated in the pathogenesis of unstable
      angina, the value of thrombus-related markers for distinguishing unstable from
      stable angina is not well defined. Fibrin D-dimer and plasminogen activator
      inhibitor were prospectively analyzed in the peripheral blood of 46 patients (26
      with unstable angina and 20 with stable angina or normal coronary arteries).
      Baseline blood samples were drawn within 24 h after rest pain in patients with
      unstable angina and in 19 of these 26 patients in less than 6 h. In patients with
      unstable angina, mean +/- SD (median) values for fibrin D-dimer and plasminogen
      activator inhibitor values measured 0.09 +/- 0.06 (0.07) microgram/ml and 9.1 +/-
      9.6 (5.9) IU, respectively, compared to 0.11 +/- 0.10 (0.05) microgram/ml and 5.5
      +/- 1.9 (5.0) IU/ml, in patients in the control group (p = NS for all comparisons
      between the two groups). Recurrent in-hospital pain, coronary anatomy and need
      for intervention showed no relation to the levels of these markers. In 19
      additional patients (9 with unstable angina and 10 control patients) samples from
      the coronary sinus and the peripheral blood were also analyzed. Again, in
      patients with unstable angina all samples were drawn less than 24 h after rest
      pain; in six of nine patients samples were drawn in less than 6 h. A coronary
      sinus to peripheral blood gradient for either of these markers could not be
      demonstrated. The differences between peripheral and coronary sinus D-dimer and
      plasminogen activator inhibitor concentrations were also similar in patients with
      unstable angina and control patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1999623
TI  - Effect of abrupt mitral regurgitation after balloon valvuloplasty on myocardial
      load and performance.
AB  - The concept that mitral regurgitation masks myocardial dysfunction by reducing
      afterload and augmenting ejection performance has not been well established in
      humans. The effect of abruptly produced mitral regurgitation on left ventricular
      loading and performance was therefore evaluated in five patients who developed
      this complication after an otherwise successful percutaneous balloon mitral
      valvuloplasty. Mitral valve area by Gorlin formula calculated with forward flow
      increased from 0.92 +/- 0.14 to 2.75 +/- 0.82 cm2. Mean left atrial pressure did
      not decrease (19 +/- 4 to 19 +/- 6 mm Hg). The size of the left atrial V wave
      relative to mean left atrial pressure (peak V - mean left atrial pressure)
      increased from 7 +/- 4 to 19 +/- 6 mm Hg. Angiographic mitral regurgitation
      increased from 0+ or 1+ to greater than 3+ in each patient and regurgitant
      fraction increased from 0.23 +/- 0.11 to 0.55 +/- 0.09 (p less than 0.01). End
      diastolic volume increased modestly from 148 +/- 15 to 159 +/- 15 ml (p = NS).
      Heart rate increased from 54 +/- 5 to 71 +/- 8 beats/min (p less than 0.05),
      which may have prevented further increases in preload by shortening the filling
      period. End-systolic stress decreased by 32% from 277 +/- 34 to 188 +/- 52
      kdyn/cm2 (p less than 0.01) as a result of a 25% decrease in end-systolic
      pressure from 121 +/- 8 to 91 +/- 7 mm Hg and a 16% decrease in end-systolic
      volume from 67 +/- 13 to 56 +/- 8 ml (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1999624
TI  - Coronary vasodilation is impaired in both hypertrophied and nonhypertrophied
      myocardium of patients with hypertrophic cardiomyopathy: a study with nitrogen-13
      ammonia and positron emission tomography.
AB  - To assess regional coronary reserve in hypertrophic cardiomyopathy, regional
      myocardial blood flow was measured in 23 patients with hypertrophic
      cardiomyopathy and 12 control subjects by means of nitrogen-13 ammonia and
      dynamic positron emission tomography. In patients with hypertrophic
      cardiomyopathy at baseline study, regional myocardial blood flow was 1.14 +/-
      0.43 ml/min per g in the hypertrophied (20 +/- 3 mm) interventricular septum and
      0.90 +/- 0.35 ml/min per g (p less than 0.05 versus septal flow) in the
      nonhypertrophied (10 +/- 2 mm) left ventricular free wall. These were not
      statistically different from the corresponding values in control subjects (1.04
      +/- 0.25 and 0.91 +/- 0.21 ml/min per g, respectively, p = NS). After
      pharmacologically induced coronary vasodilation (dipyridamole, 0.56 mg/kg
      intravenously over 4 min), regional myocardial blood flow in patients with
      hypertrophic cardiomyopathy increased significantly less than in control subjects
      both in the septum (1.63 +/- 0.58 versus 2.99 +/- 1.06 ml/min per g, p less than
      0.001) and in the free wall (1.47 +/- 0.58 versus 2.44 +/- 0.82 ml/min per g, p
      less than 0.001). In addition, patients with hypertrophic cardiomyopathy who had
      a history of chest pain had more pronounced impairment of coronary vasodilator
      reserve than did those without a history of chest pain. After dipyridamole,
      coronary resistance in the septum decreased by 38% in patients without a history
      of chest pain, but decreased by only 14% in those with such a history (p less
      than 0.05). Coronary resistance in the free wall decreased by 45% in patients
      without and by 27% in those with a history of chest pain (p = 0.06).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1999625
TI  - Mechanisms for left ventricular systolic dysfunction in aortic regurgitation:
      importance for predicting the functional response to aortic valve replacement.
AB  - To test the hypothesis that the combined use of the time-varying elastance
      concept and conventional circumferential stress-shortening relations would
      elucidate differential mechanisms for left ventricular systolic dysfunction in
      severe, chronic aortic regurgitation and therefore predict the functional
      responses to aortic valve replacement, 31 control patients and 37 patients with
      aortic regurgitation were studied. The studies included micromanometer left
      ventricular pressure determinations, biplane contrast cineangiograms under
      control conditions and radionuclide angiograms under control conditions and
      during methoxamine or nitroprusside infusions with right atrial pacing. The
      patients with aortic regurgitation were classified into three groups: Group I had
      normal Emax and stress-shortening relations, Group II had abnormal Emax but
      normal stress-shortening relations and Group III had abnormal Emax and stress
      shortening relations. The left ventricular end-diastolic and end-systolic volumes
      showed a progressive increase and the ejection fraction showed a progressive
      decrease from Group I to III; these values differed from those in the control
      patients (p less than 0.001). In Group I, there was a decrease in left
      ventricular volumes (p less than 0.05) but no significant change in ejection
      fraction (61 +/- 7% versus 63 +/- 4%) after aortic valve replacement. In
      contrast, in Group II, reduction in left ventricular volumes (p less than 0.01)
      was associated with an increase in ejection fraction from 50 +/- 8% to 64 +/- 11%
      (p less than 0.01). Finally, in Group III, reduction in left ventricular volumes
      (p less than 0.05) was associated with a further decrement in ejection fraction
      from 35 +/- 13% to 30 +/- 13%. Group I patients had compensated adequately for
      chronic volume overload. However, Group II had left ventricular dysfunction that
      was associated with an increase in the left ventricular volume/mass ratio
      compared with that in the control patients and Group I (p less than 0.05 for
      both), suggesting inadequate hypertrophy and assumption of spherical geometry.
      Finally, irreversible myocardial dysfunction had supervened in Group III. In
      conclusion, a combined analysis of left ventricular chamber performance using the
      time-varying elastance concept and myocardial performance using conventional
      circumferential stress-shortening relations provides complementary information
      that elucidates differential mechanisms for left ventricular systolic dysfunction
      and therefore predicts the functional response to aortic valve replacement.

PMID- 1999626
TI  - Aortic regurgitation: the need for an integrated physiologic approach.

PMID- 1999628
TI  - Patient age and results of balloon aortic valvuloplasty: the Mansfield Scientific
      Registry experience. The Mansfield Scientific Aortic Valvuloplasty Registry
      Investigators.
AB  - Patients enrolled in the Mansfield Scientific Aortic Valvuloplasty Registry were
      followed up a mean of 7 months after balloon aortic valvuloplasty. Results were
      compared for patients less than 70, 70 to 79 and greater than or equal to 80
      years of age at time of valvuloplasty. As assessed by aortic valve area indexed
      to body surface area, stenosis was more severe in the older patients and the
      incidence of congestive heart failure was also greater in those aged greater than
      or equal to 80 years. The results of valvuloplasty were comparable in all three
      age groups, and indexed final valve area was not significantly different among
      the groups. In-hospital mortality ranged from 4.2% to 9.4%, but this and other
      complications were not significantly different among the groups. Total 7 month
      mortality was 23%. As performed in this registry study, balloon aortic
      valvuloplasty produced similar results in older and younger patients, despite
      initially more severe disease in the older patients.

PMID- 1999627
TI  - Impact of orifice geometry on the shape of jets: an in vitro Doppler color flow
      study.
AB  - To investigate the influence of orifice geometry on the three-dimensional shape
      of jets, an in vitro Doppler color flow study was performed. Jets were formed by
      discharging blood through round orifices and through orifices with major/minor
      axis ratios of 2:1, 3:1 and 5:1. These were repeated with orifice areas of 0.1,
      0.3 and 0.5 cm2. For turbulent and laminar jets formed by these orifices, Doppler
      color flow images were obtained from two orthogonal scanning planes aligned with
      the major and minor orifice axes. Jet width was measured at 1 cm intervals from 0
      to 5 cm from the orifice and used to calculate jet eccentricity (ratio of major
      to minor axis widths) and the rate of divergence of the jet walls. Jets were
      observed to diverge more rapidly along walls aligned with the orifice minor axis
      rather than along the major axis. This differential spreading led to the
      development of circular symmetry at a short distance from the orifice. Jet
      divergence (theta) occurred more rapidly for turbulent jets and for jets formed
      by larger orifices: theta (zero) = 0.80 + 6.3.A + 7.0.T + 0.47.E-OR (r = 95, p
      less than 0.0001, n = 48), where A is orifice area (cm2); T is 0 for laminar
      jets, 1 for turbulent jets and E-OR combines orifice eccentricity and scanning
      orientation, ranging from -5 for 5:1 orifices imaged along the major axis, 0 for
      circular orifices to 5 for 5:1 orifices imaged along the minor axis. Within the
      jet, eccentricity decayed approximately exponentially with distance from the
      orifice, more rapidly for turbulent jets, more slowly for the larger and more
      eccentric orifices.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1999629
TI  - Drug response at electropharmacologic study in patients with ventricular
      tachyarrhythmias: the importance of ventricular refractoriness.
AB  - The clinical and electrophysiologic predictors of successful antiarrhythmic drug
      therapy for patients with inducible ventricular tachycardia were evaluated in 59
      consecutive patients undergoing serial electropharmacologic trials. Structural
      heart disease was less frequently present in patients for whom effective therapy
      was found (p less than 0.05). The presence of coronary artery disease and a
      history of prior myocardial infarction were significantly more frequently present
      in patients for whom antiarrhythmic drug therapy could not be found (p less than
      0.05). The corrected QT interval and ventricular effective refractory period
      measured at a pacing cycle length of 400 ms were significantly shorter in
      responders compared with nonresponders (QT interval 428 +/- 52 versus 460 +/- 59
      ms; ventricular effective refractory period 237 +/- 28 versus 254 +/- 24 ms; (p
      less than 0.05). In addition, the interelectrogram coupling interval of the
      ventricular extrastimulus initiating ventricular tachycardia was significantly
      shorter in responders compared with nonresponders (223 +/- 37 versus 251 +/- 33
      ms; p = 0.003). Logistic regression analysis identified a short ventricular
      interelectrogram coupling interval (p less than 0.01) and absence of prior
      myocardial infarction (p less than 0.05) as the only independent predictors of
      antiarrhythmic drug suppression of the induction of ventricular tachycardia.
      Greater drug-induced increments in the ventricular effective and functional
      refractory periods were observed in responders than in nonresponders as was the
      shortest ventricular interelectrogram coupling interval. Thus, baseline
      electrophysiologic measurements identify patients with inducible ventricular
      tachycardia who are likely to respond to antiarrhythmic drug therapy.
      Furthermore, these patients demonstrate greater drug-induced electrophysiologic
      changes.

PMID- 1999630
TI  - Morphologic comparison of patients with mitral valve prolapse who died suddenly
      with patients who died from severe valvular dysfunction or other conditions.
AB  - Clinical and necropsy findings are described in 56 patients with mitral valve
      prolapse: 15 patients, aged 16 to 69 years (mean 39), died suddenly and mitral
      valve prolapse was the only cardiac condition found at necropsy (hereafter called
      isolated mitral valve prolapse); the remaining 41 patients had other conditions
      that were capable of being fatal. Of the latter 41 patients, 7, aged 17 to 59
      years (mean 45), had associated congenital heart disease, and 34 patients, aged
      17 to 70 years (mean 52), had no associated congenital cardiac abnormalities.
      Compared with the 34 patients without associated congenital heart disease and
      with nonmitral valve prolapse conditions capable in themselves of being fatal,
      the 15 patients who died suddenly with isolated mitral valve prolapse were
      younger (mean age 39 +/- 17 versus 52 +/- 15 years; p = 0.01), more often women
      (67% versus 26%; p = 0.008) and had a lower frequency of mitral regurgitation (7%
      versus 38%; p = 0.02). The 15 patients dying suddenly with isolated mitral valve
      prolapse also were less likely to have evidence of ruptured chordae tendineae
      (29% versus 67%; p = 0.04). The frequency of increased heart weight (67% versus
      59%), a dilated mitral valve anulus (80% versus 81%), a dilated tricuspid valve
      anulus (17% versus 17%), an elongated anterior mitral leaflet (86% versus 54%),
      an elongated posterior mitral leaflet (79% versus 77%) and fibrous endocardial
      plaque under the posterior mitral leaflet (73% versus 63%) was similar between
      the two groups. The severity of the prolapse (mild 20% versus 11%; moderate 27%
      versus 58%; severe 53% versus 32%) also was similar between the two groups. Thus,
      persons with mitral valve prolapse dying suddenly without another recognized
      condition tend to be relatively young women without mitral regurgitation.

PMID- 1999631
TI  - Tricuspid atresia or severe stenosis with partial common atrioventricular canal:
      anatomic data, clinical profile and surgical considerations.
AB  - The anatomic findings in 11 cases of tricuspid atresia and in two cases of severe
      tricuspid stenosis, both combined with partial common atrioventricular (AV)
      canal, are presented in detail. Twelve cases were documented by postmortem
      examination and the diagnosis was confirmed by echocardiography and surgical
      observation in the one living patient. Clinical data available in nine cases and
      cardiac catheterization data obtained in eight are included in this report. In
      three cases (23%)--two with tricuspid atresia and one with extreme tricuspid
      stenosis--the tricuspid valve and right ventricle exhibited characteristics seen
      in Ebstein's anomaly. In all 13 cases, the great arteries were normally related.
      The ventricular septal defect(s) in 10 (83%) of the 12 postmortem cases rapidly
      became smaller and this resulted in marked diminution of the pulmonary blood flow
      and severe hypoxia. Only three of the eight patients with available cardiac
      catheterization and angiocardiographic data showed the scooped-out appearance of
      the left ventricular septal surface characteristic of AV canal defects. By
      contrast, two-dimensional echocardiography, available in the three most recent
      cases, accurately demonstrated all the defects present and represents the
      diagnostic method of choice. Early surgical intervention to establish a systemic
      to pulmonary artery anastomosis is essential for survival. More definitive
      surgical treatment can be achieved later by an atriopulmonary or cavopulmonary
      anastomosis with or without replacement of the cleft and often regurgitant mitral
      valve. The one living patient exemplifies this approach. This is the largest
      series of this unusual type of tricuspid atresia reported to date.

PMID- 1999632
TI  - Tricuspid valve dysplasia or displacement in intrauterine life.
AB  - In 450 cases of structural heart disease diagnosed prenatally, 38 fetuses (8.5%)
      had either a dysplastic or a displaced tricuspid valve. The tricuspid valve was
      dysplastic in 22 fetuses, all of which had evidence of tricuspid regurgitation
      resulting in right atrial dilation and increased cardiothoracic ratio. An
      associated abnormality of the pulmonary valve occurred in 16 fetuses. The
      remaining 16 fetuses had Ebstein's malformation, 14 with evidence of tricuspid
      incompetence at presentation and 10 with an associated abnormality of the
      pulmonary valve. Of the 38 cases, the pregnancy was interrupted in 17,
      spontaneous intrauterine fetal death occurred in 8, 11 infants died postnatally
      and 2 infants are still alive; additional abnormalities were found in 8 cases
      (chromosomal anomalies in 2, ventricular septal defects in 2, corrected
      transposition in 2, the Chiari malformation in 2, supraventricular tachycardia in
      1 case and coarctation of the aorta in 1). Fetuses with severe abnormalities are
      selected for fetal echocardiography by the four chamber screening program and a
      high rate of natural loss both in intrauterine life and immediately after birth
      was observed in the 21 cases in which pregnancy was continued. This would explain
      the higher incidence of tricuspid valve disease in our prenatal compared with
      postnatal series. Although increased cardiothoracic ratio and associated lesions
      of the right ventricular outflow tract contribute to the poor outcome in the
      cases detected prenatally, the absence of these features does not always indicate
      a good prognosis because progression of disease can occur with advancing
      gestational age. No absolute measurement or single echocardiographic feature
      emerged as a consistent predictive factor of prognosis.

PMID- 1999633
TI  - Aortico-left ventricular tunnel: long-term outcome after surgical repair.
AB  - Over a 14 year period, four children (three male, one female) underwent surgical
      correction of an aortico-left ventricular tunnel. All presented in infancy (age
      range 5 days to 9 months). The presenting feature was a systolic and diastolic
      murmur in all, one of whom developed heart failure within 2 weeks of
      presentation. In the first two patients, the echocardiographic findings were
      inconclusive and the diagnosis was confirmed at cardiac catheterization (at 10
      and 23 months of age, respectively); the other two were diagnosed
      echocardiographically by two-dimensional and Doppler color flow imaging. All four
      patients underwent surgery by patch closure of the aortic end of the tunnel
      (three patients) or direct suture closure (one patient) and there were no deaths.
      The mean age at operation was 11 months. During a mean follow-up period of 71
      months (range 2 to 157), three patients have clinical and echocardiographic
      evidence of trivial aortic valve regurgitation, which was noted in the immediate
      postoperative period in one and at early (less than 6 months) follow-up study in
      the other two. All are symptom-free, are taking no medications and are growing
      and developing normally. Aortico-left ventricular tunnel can be accurately
      diagnosed by echocardiography. In patients presenting in infancy,
      echocardiography also provides the necessary morphologic information to enable
      surgical correction without angiography. Early operation is associated with an
      excellent outcome, whereas repair at a later age is associated with a high
      incidence of residual aortic regurgitation requiring further surgery.

PMID- 1999634
TI  - Anti-ischemic effects of atenolol versus nifedipine in patients with coronary
      artery disease and ambulatory silent ischemia.
AB  - The anti-ischemic effects of atenolol and nifedipine were compared in a
      randomized double-blind crossover manner in 24 patients with stable exertional
      angina and transient silent ischemia during ambulatory electrocardiographic (ECG)
      monitoring. Both atenolol and nifedipine were effective (p less than 0.005) in
      reducing the average number and duration of transient ischemic events, but
      therapy with atenolol was associated with a significantly greater reduction in
      the mean number (p less than 0.05) and duration (p less than 0.01) of silent
      ischemic events. Analyses of the silent ischemic activity during the morning
      hours revealed that only therapy with atenolol produced a significant reduction
      in the average duration per patient (139 +/- 54 vs. 1,609 +/- 468 s, p less than
      0.01) and in the average duration of silent ischemia per event between 6 AM and
      12 noon (62 +/- 21 vs. 208 +/- 24 s, p less than 0.005). There were fewer adverse
      experiences during therapy with atenolol. These results show that although both
      atenolol and nifedipine are effective in reducing silent ischemic events,
      treatment with atenolol is associated with significantly greater efficacy,
      particularly on the morning surge of silent myocardial ischemia.

PMID- 1999635
TI  - Sinus node-atrioventricular node isolation: long-term results with the "corridor"
      operation for atrial fibrillation.
AB  - The "corridor" operation is designed to restore sinus rhythm to patients with
      atrial fibrillation by electrically isolating the sinus node, a band of atrial
      tissue and the atrioventricular (AV) node from the remaining atrial tissue. Nine
      patients with drug-refractory atrial fibrillation underwent this operation; four
      patients had chronic atrial fibrillation and five had paroxysmal atrial
      fibrillation; the mean duration of symptoms was 12 +/- 8 years. Patient ages
      ranged from 25 to 68 years (mean 48 +/- 12). At preoperative electrophysiologic
      study, no patient had evidence of an accessory AV pathway or AV node reentry.
      Sinus node recovery time could not be determined in five patients because of
      recurrent atrial fibrillation during or before programmed stimulation. At
      operation the corridor of atrial tissue connecting the sinus and AV nodes was
      successfully isolated from the remaining left and right atrial tissue in all
      patients. One patient required early reoperation for recurrent atrial
      fibrillation before hospital discharge. At the predischarge electrophysiologic
      study, the corridor remained isolated in all patients except for one patient who
      had intermittent conduction between the corridor and excluded right atrium. One
      patient had nonsustained atrial fibrillation and one had atrial tachycardia
      evident in the corridor. Atypical AV node reentry of uncertain significance was
      induced in one other patient. Over a total follow-up of 191 patient months (mean
      21 +/- 20), seven patients remained free of atrial fibrillation. Two patients had
      recurrent atrial fibrillation, which in one patient was effectively controlled by
      a single antiarrhythmic agent. A permanent pacemaker was implanted in four
      patients for sinus node dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1999636
TI  - Surgical therapy for atrial fibrillation: a first step on what may be a long
      road.

PMID- 1999637
TI  - Acute biologic response to excimer versus thermal laser angioplasty in
      experimental atherosclerosis.
AB  - Vascular injury and platelet accumulation after balloon angioplasty are two
      potentially important triggers of the process of restenosis that may be minimized
      by the use of laser energy to ablate atherosclerotic plaque. The type of laser
      most suitable to achieve these goals remains unknown. Accordingly, angiographic
      and histologic studies and quantitative platelet deposition analysis were
      performed on 27 atherosclerotic rabbit iliac arteries randomized to treatment
      with excimer laser or thermal laser angioplasty. Excimer laser angioplasty was
      achieved with 35 to 40 mJ/mm2 of 308 nm xenon chloride irradiation delivered
      through a 4.5F catheter made of 13 concentrically arranged 200 microns fiber
      optics, at a repetition rate of 25 to 30 Hz and a pulse duration of 135 ns;
      thermal laser angioplasty was achieved with a 1.7 mm metal probe heated with 10 W
      of continuous wave argon laser energy. The baseline and post-laser luminal
      diameters of excimer laser-treated vessels (0.92 +/- 0.28 and 1.56 +/- 0.48 mm,
      respectively) were similar to those observed in thermal laser-treated vessels
      (1.05 +/- 0.44 and 1.61 +/- 0.41 mm, respectively). Perforation occurred in 4
      (29%) of 14 thermal laser-treated arteries and in 0 of 13 excimer laser-treated
      arteries (p = 0.04); spasm was observed in only 1 thermal laser-treated vessel.
      On the basis of a quantitative histologic grading scheme (damage scores of 0 to
      4), greater degrees of injury were measured in thermal versus excimer laser
      treated vessels (2.4 +/- 1.0 versus 1.3 +/- 0.4, p = 0.009).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1999638
TI  - Value of ventricular electrogram recordings in the diagnosis of arrhythmias
      precipitating electrical device shock therapy.
AB  - An antitachycardia pacemaker-cardioverter-defibrillator that is capable of
      storing ventricular electrograms before and after delivery of device shock
      therapy was implanted in 16 patients. Three of the patients experienced out-of
      hospital device shock therapy preceded by minimal symptoms. Although limitations
      of electrogram analysis exist and are discussed, careful analysis and
      registration of electrograms during all supraventricular and ventricular rhythms
      observed during in-hospital testing served as an important reference for
      subsequent arrhythmia diagnosis. By analyzing the electrogram rate and RR
      interval stability and configuration, a definitive diagnosis was established in
      all three patients (atrial fibrillation, polymorphic ventricular tachycardia and
      rate-sensing lead disruption, respectively). Thus, the ability to store
      ventricular electrograms before shock therapy represents a major advance in the
      management of patients who receive an electrical device to treat ventricular
      tachyarrhythmia.

PMID- 1999639
TI  - Smooth muscle cell proliferation and restenosis after stand alone coronary
      excimer laser angioplasty.
AB  - It has been shown that coronary excimer laser angioplasty can remove
      atherosclerotic intracoronary tissue. Stand alone coronary excimer laser
      angioplasty was successfully performed in a 53 year old white man with 90%
      stenosis of the left anterior descending coronary artery and exertional angina
      (Canadian Cardiovascular Society class III). The lesion was reduced to a 30%
      residual stenosis with use of a 1.2 mm and subsequently a 1.8 mm diameter laser
      catheter. Early follow-up angiography 24 h later revealed persistent patency and
      unchanged lesion diameter of the target vessel. The patient was free of symptoms
      during the 2 month follow-up period, but died suddenly while playing in a tennis
      tournament 63 days after the procedure. Postmortem histologic examination
      revealed 80% restenosis at the lesion site without plaque disruption or
      thrombosis. Specific staining of the histologic specimen for smooth muscle cells
      using alpha-actin revealed significant smooth muscle cell proliferation at the
      site of coronary excimer laser angioplasty. However, most of the vessel narrowing
      appeared to be due to underlying fibrotic plaque as a result of insufficient
      tissue ablation. This was probably related to the size of the currently available
      catheters, which are too small to create a large channel.

PMID- 1999640
TI  - Early limitations of coronary excimer laser angioplasty.

PMID- 1999641
TI  - President's page: RBRVS in review.

PMID- 1999642
TI  - Methicillin-resistant Staphylococcus aureus in extended-care facilities:
      experiences in a Veterans' Affairs nursing home and a review of the literature.
AB  - OBJECTIVES: To delineate the spread of methicillin-resistant Staphylococcus
      aureus (MRSA) in a nursing home care unit (NHCU), determine its consequences, and
      discuss this experience in the context of reports from other nursing homes.
      DESIGN: Observational and descriptive; routine and special surveillance for MRSA,
      including a facility-wide prevalence survey; characterization of MRSA isolates by
      disk diffusion and agar dilution susceptibility studies and restriction enzyme
      analysis of plasmid (REAP) DNA. SETTING AND PATIENTS: A 120-bed skilled nursing
      facility that is an integral part of the Veterans' Affairs Medical Center (VAMC),
      Portland, Oregon. The patients are predominantly elderly men with severe
      underlying diseases and functional impairments. RESULTS: An asymptomatic carrier
      brought MRSA into the NHCU in December 1987. During the next 15 months, 24
      additional MRSA cases were detected. A prevalence survey conducted in March 1989
      indicated that 39 (34%) of the 114 patients and 8 (7%) of the 117 employees were
      colonized or infected with MRSA. All strains were resistant to ciprofloxacin.
      REAP DNA indicated that 37 of 41 strains recovered in the March survey had
      identical patterns. Although 16 episodes of MRSA infection occurred in NHCU
      residents during 1988 through 1989, the outbreak had little effect on overall
      patterns of infectious morbidity and mortality in the facility. The outbreak,
      however, did result in an increased MRSA caseload at the medical center's acute
      care division. CONCLUSIONS: During the last three years, MRSA colonization and
      infection have become common in the NHCU at the Portland VAMC; this experience
      parallels that reported by several nursing homes in other parts of the country.

PMID- 1999643
TI  - Should we vigorously try to contain and control methicillin-resistant
      Staphylococcus aureus?
AB  - OBJECTIVE: To review practices currently used to control transmission of
      methicillin-resistant Staphylococcus aureus (MRSA) in hospitals, determine the
      frequency of their use, and discuss the indications for implementing such
      measures. DESIGN: A questionnaire survey to determine how commonly selected
      control practices are used, and a literature review of the efficacy of control
      practices. PARTICIPANTS: Two hundred fifty-six of 360 hospital-based members fo
      the Society for Hospital Epidemiology of America, Inc. (SHEA) completed the
      survey questionnaire. RESULTS: Many different combinations of surveillance and
      control measures are used by hospitals with MRSA. Nine percent of hospitals
      stated that no special measures were used to control MRSA. The efficacy of
      commonly used control measures has not been established by controlled trials.
      CONCLUSIONS: Implementing control measures is warranted when MRSA causes a high
      incidence of serious nosocomial infections, and is desirable when MRSA has been
      newly introduced into a hospital or into an intensive care unit, or when MRSA
      accounts for more than 10% of nosocomial staphylococcal isolates. While the value
      of some practices is well established, measures such as routinely attempting to
      eradicate carriage of MRSA by colonized patients and personnel require further
      evaluation.

PMID- 1999644
TI  - Infection surveillance in long-term care facilities.

PMID- 1999645
TI  - Nosocomial transmission and infection control aspects of parasitic and
      ectoparasitic diseases: Part I. Introduction/enteric parasites.

PMID- 1999646
TI  - Methicillin-resistant Staphylococcus aureus.

PMID- 1999647
TI  - Purification of a murine monoclonal antibody of the IgM class.
AB  - A simple method is described for the purification of murine monoclonal antibodies
      of the IgM class. Ascites fluid was subjected to ammonium sulfate precipitation.
      The precipitate was redissolved and dialyzed and subsequently subjected to gel
      filtration chromatography on Ultrogel AcA22 and finally ion exchange
      chromatography on DEAE-Sepharose. The purity of the antibody was assessed by
      reducing SDS gel electrophoresis, and estimated to be greater than 85% pure after
      gel filtration, and greater than 95% pure after the ion exchange chromatography.
      The immuno-activity of the antibody was assessed throughout the purification
      scheme by the ability of the antibody to bind to immunogen immobilized to
      nitrocellulose. Approximately 50% antibody activity was recovered from this
      purification scheme after gel filtration, but only 10% of the initial activity
      could be recovered after ion exchange chromatography. This result with ion
      exchange chromatography underscores the lability of IgM antibodies to
      immobilization. Therefore, if the recovery of immunoreactive IgM antibody is a
      goal, purification schemes of IgM antibodies should avoid ion exchange or
      affinity chromatography.

PMID- 1999648
TI  - Detection of IgA binding site by flow cytometry with fluorescent microspheres.
AB  - To establish a sensitive method to detect IgA Fc receptors (Fc alpha R) on human
      and murine lymphoid cells, fluorescent microspheres (FMS) were used in a flow
      cytometric assay. The following three assays with FMS were tested and compared
      with a conventional indirect Fc alpha R assay using FITC-labeled anti-IgA: (1)
      direct cell binding assay with murine myeloma IgA(MOPC315)-coated FMS(IgA-FMS
      assay), (2) indirect assay with TNP-BSA-coated FMS which bind to cells
      preincubated with MOPC315 IgA bearing anti-TNP activity (TNP-BSA-FMS assay), and
      (3) indirect assay with anti-IgA coated FMS after preincubation of the cells with
      IgA(anti-IgA-FMS assay). In these three assays for Fc alpha R using FMS, the
      binding of IgA to the cells was not affected by purified IgM or IgG preparations.
      In both indirect assays using TNP-BSA-FMS and anti-IgA-FMS, sharp and dose
      dependent IgA binding was obtained at lower IgA concentrations ranging from 4 to
      125 micrograms/ml as compared with the conventional indirect assay. The
      background MFI levels in all these FMS assays remained as low as those in the
      conventional assay. These findings suggest that FMS coupled with TNP-BSA or anti
      IgA antibodies is suitable for the detection of Fc alpha R on both murine and
      human T cells.

PMID- 1999649
TI  - Efficient induction of Semliki Forest virus and mumps virus neutralizing anti
      anti-idiotypic antibodies using Quil A as adjuvant.
AB  - Rabbit anti-idiotypic sera were prepared against Semliki Forest virus (SFV)
      neutralizing monoclonal antibody (MAb) UM 1.13 and mumps virus neutralizing MAb
      UM 10B. From these sera anti-idiotypic antibodies were purified by ammonium
      sulphate precipitation and subsequent affinity column chromatography. Anti-iso-
      and anti-allotypic antibodies were removed by binding to normal mouse serum
      immunoglobulins coupled to CNBr activated Sepharose. Peak protein fractions
      eluted from columns loaded with homologous MAb were used for anti-anti-idiotypic
      immunization of BALB/c mice to raise virus neutralizing anti-anti-idiotypic
      antibodies. Two intracutaneous immunizations, five weeks apart, with affinity
      purified rabbit polyclonal anti-idiotypic antibody (40 micrograms protein per
      animal) coupled to keyhole limpet hemocyanin and mixed with the adjuvant Quil A
      (50 microliters per animal) were sufficient to evoke neutralizing antibodies
      against either virus. Moreover the mice who developed SFV neutralizing serum
      antibodies upon anti-idiotypic immunization all survived an otherwise lethal
      challenge with virulent SFV.

PMID- 1999650
TI  - The use of a hapten-Fab conjugate to sensitize target cells for antibody
      dependent complement-mediated lysis and antibody-dependent cell-mediated
      cytotoxicity.
AB  - NIP-conjugated Fab' fragments from a rabbit hyperimmunized with sheep red blood
      cells (SRBC) were used to link the hapten NIP to target cells for antibody
      dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent complement
      mediated lysis (ADCML). Target cells (SRBC) labelled with this NIP-Fab' complex
      were compared with SRBC directly haptenized with NIP in ADCC and ADCML assays
      using a NIP specific IgG1 chimeric antibody. Both methods yielded almost
      identical results. Using the NIP-FAb' conjugate identical target cell
      haptenization was readily achieved from experiment to experiment. Using
      conjugates of different NIP/Fab' ratios it should be possible to study how such
      changes influence antibody effector functions.

PMID- 1999651
TI  - Recombinant fusion proteins of protein A and protein G with glutathione S
      transferase as reporter molecules.
AB  - The regions encoding the IgG-binding domains of protein A (PA) and protein G (PG)
      were cloned into the bacterial expression vector pGEX. Both proteins were
      expressed in Escherichia coli as fusion proteins with glutathione S-transferase
      (PA-GST and PG-GST) and were found to be soluble, abundant and easily purified in
      one step from the bacterial lysate by affinity chromatography on immobilized
      glutathione. Yields of 50 mg/litre of cultures were obtained. Both purified
      fusion proteins were shown to be functional in a variety of immunochemical
      procedures. In radial diffusion tests, PA-GST precipitated IgG from human,
      squirrel monkey, rabbit, dog, cat and pig but not mouse, sheep, goat, cow, horse
      or chicken. PG-GST formed precipitin bands with IgG from human, rabbit, mouse,
      pig, sheep, goat, cow and horse but not squirrel monkey, dog, cat and chicken
      IgG. The fusion proteins were shown to function as effective detection reagents
      in ELISA and Western blotting. Glutathione agarose beads with bound fusion
      protein were shown to be useful for immunoprecipitation.

PMID- 1999652
TI  - Enzyme-linked immunosorbent assay (ELISA) for HIV antibody by a glass slide
      technique.
AB  - An enzyme-linked immunosorbent assay (ELISA) technique is described which
      utilizes a commercially available glass microscope slide coated with hydrophobic
      teflon in such a pattern as to give 30 small circular wells, each of which has a
      glass bottom. Each well serves as a solid phase, analogous to a microtiter well
      for adsorption of purified human immunodeficiency virus (HIV) antigens. Since
      only 5-10 microliter volumes of reagents are used and rinsing processing is
      simple, the cost per test is much less than most other ELISA technologies. HIV
      antigen is stable for over 1 year at 37 degrees C when dried on the glass slides.
      The sensitivity and specificity of the micro slide immunoenzymatic assay (Micro
      SIA) was studied by testing randomly selected, known HIV-seropositive and
      seronegative plasma. Results compare well with microtiter and Western blot
      assays. A simple vertical-beam colorimeter is described (useful in the Micro-SIA)
      which can be easily assembled by the user from commonly available components.

PMID- 1999653
TI  - Two distinct monoclonal antibodies raised against mouse beta nerve growth factor.
      Generation of bi-specific anti-nerve growth factor anti-horseradish peroxidase
      antibodies for use in a homogeneous enzyme immunoassay.
AB  - Two hybridomas producing monoclonal antibodies against mouse beta nerve growth
      factor (NGF) were obtained from the fusion of hyperimmune splenocytes from rats
      immunized with polymerized beta-NGF and Sp2/0.Ag mouse myeloma cells. The
      monoclonal antibodies coded IgG 24 and 30 produced and secreted by the hybrid
      cells are both of the IgG2a subclass. Both monoclonal antibodies are capable of
      recognizing native NGF coated on microassay plates as well as the denatured
      factor on Western blots. However, only IgG 30 has been found to block NGF-induced
      process outgrowth from the rat pheochromocytoma cell line (PC12) as well as NGF
      induced increase in choline acetyltransferase activity in rat primary septal cell
      cultures. In addition, only IgG 30 was able to detect immunocytochemically NGF
      immunoreactive sites in fixed tissue. And, finally, IgG 24 could not compete for
      IgG 30 binding to immobilized native NGF. Consequently, it appears that these
      antibodies are recognizing different epitopes on the NGF molecule. Neither
      monoclonal antibody displayed any crossreactivity with serum albumin, aprotinin,
      epidermal growth factor or insulin. A hybrid-hybridoma producing bi-specific anti
      NGF anti-horseradish peroxidase (HRP) monoclonal antibodies was generated from
      the fusion of an azaguanine resistant anti-HRP hybridoma, coded RAP2.Ag and the
      anti-NGF IgG 30 hybridoma treated with emetine. The potential merits of using
      these bi-specific antibodies in combination with their mono-specific anti-NGF
      parent in a homogeneous sandwich immunoassay for the quantitation of NGF are
      discussed.

PMID- 1999654
TI  - Characterisation of monoclonal antibodies to human factor X/Xa. Initial
      observations with a quantitative ELISA procedure.
AB  - Monoclonal antibodies to human plasma factor X (FX) and factor Xa (FXa) have been
      developed using several modifications of previously described techniques. These
      include the use of footpad immunisation with a suspension of free and
      nitrocellulose-bound antigen with subsequent fusion of popliteal lymph node
      cells. From a panel of 17 reactive hybridomas to FX, 3 were selected for further
      characterisation. An additional hybridoma reactive to FXa but not FX was also
      selected. Two monoclonal antibodies designated FX52 and FX64 were specific for FX
      with no reactivity to FXa, while antibody FXa24 was specific for FXa. Another
      FX/FXa95 reacted with both FX and FXa. All selected antibodies were of the IgG
      isotype and reacted both with native antigen and antigen transferred to
      nitrocellulose by Western blotting. Initial observations suggest that Mab FX52
      may be used to quantitate FX levels in plasma.

PMID- 1999655
TI  - Optimization of binding capacity and specificity of protein G on various solid
      matrices for immunoglobulins.
AB  - Streptococcal protein G is a more versatile and efficient alternative to
      staphylococcal protein A in purifying immunoglobin G (IgG) isotypes from various
      animal species. Optimizations are most dramatic with goat IgG, which binds
      protein G 55 times better than protein A. Using GammaBind G (a recombinant form
      of protein G (Genex Corp.)), we optimized binding capacity and specificity for
      IgG. Protein G was covalently coupled to three different matrices (CNBr
      Sepharose, Tresyl-Sepharose, and Affigel-10) and compared with protein A-CNBr
      Sepharose. Equal volumes of human, mouse, and goat serum samples were
      equilibrated into Hepes/NaOH buffers with various ionic strengths (i.e.,
      concentrations of NaCl) and pH values and allowed to bind to affinity columns of
      proteins G and A. Bound ligands were eluted with 8.0 M urea, 0.05-M Tris/HCl, pH
      8.00. Bound fractions were assayed for protein concentration and analyzed by
      sodium dodecyl sulfate polyacrylamide electrophoresis. The optimal conditions for
      binding IgG to protein G are 1.0 M NaCl and pH 8.0 for human, mouse, and goat.

PMID- 1999656
TI  - In vivo anti-complementary activities of the cobra venom factors from Naja naja
      and Naja haje.
AB  - The kinetics of complement (C) depletion and recovery of C levels upon injection
      of BALB/c mice with cobra venom factors (CVF), from N. naja (C3- and C5
      depleting) and N. haje (selectively C3-depleting) were studied. The animals
      received i.p. or i.v. injections of either of the two preparations. CH50 and
      hemolytic C3 and C5 levels were followed as parameters of residual complement
      activity. N. naja CVF turned out to be as efficient in depleting total complement
      activity as N. haje CVF. Decreased CH50 values could largely be ascribed to C3
      depletion. Complement consumption after N. naja CVF, however, lasted longer than
      after N. haje CVF administration. Estimated functional half-lives of N. naja and
      N. haje CVF were 11.5 and 4.5 h, respectively. Inhibition ELISAs showed that,
      after in vivo administration of either of the two CVF preparations, antigenic C3
      and C5 kept circulating for days.

PMID- 1999657
TI  - Patrick Watson-Williams and the concept of focal sepsis in the sinuses: an
      historical caveat for functional endoscopic sinus surgery.
AB  - From 1900 to 1940 the theory of focal sepsis was invoked to justify a number of
      dubious surgical procedures. Surgeons believed they were acting rationally.
      Patrick Watson-Williams advocated suction exploration of the paranasal sinuses
      for mental patients, claiming to cure criminal insanity by sphenoidotomy.
      Favourable contemporary reviews showed international approval. The rational basis
      of treatment was emphasised, but there was little systematic evaluation of
      outcome. Current enthusiasm for functional endoscopic sinus surgery is also based
      on a rational approach, logical deductions from pathophysiological 'facts'.
      Outcome has still not been evaluated scientifically. We should learn from
      history. Treatment should not be based too readily on what seems to be rational
      now. Ideas of physiology and pathology change. What seems logical today may
      appear ridiculous tomorrow. Careful analysis of outcome, preferably by controlled
      clinical trials, is needed as a rational treatment requires empirical validation
      just as much as any other.

PMID- 1999658
TI  - A double-blind, placebo-controlled trial of beclomethasone dipropionate 600
      micrograms/day in the treatment of non-atopic rhinitis.

PMID- 1999659
TI  - 'Two-stage turbinectomy': sequestration of the inferior turbinate following
      submucosal diathermy.
AB  - Submucous diathermy of the inferior turbinates is a widely practised procedure.
      Three cases are presented in which surgery was complicated by avascular necrosis
      of the turbinate bone. Each patient required a debridement procedure before
      healing and recovery of normal mucociliary function could take place.

PMID- 1999661
TI  - Limited CT scanning techniques of the paranasal sinuses.
AB  - Computerized tomographic (CT) imaging provides detailed information on the
      paranasal sinuses and is now well established as an alternative to standard
      radiographs. The planning and safety of surgery to the paranasal sinuses is
      greatly improved by CT imaging. We describe a new CT protocol comprising a
      limited coronal and axial scan series, based on our experience with the
      previously described 'CT-Mini-series'.

PMID- 1999660
TI  - Management of posterior epistaxis with the use of the fibreoptic
      nasolaryngoscope.
AB  - Posterior epistaxis is usually treated by repeated nasal packing and in failed
      situations by ligation of feeding arteries with considerable morbidity and
      mortality. The most logical approach should be location of the bleeding site and
      arrest of haemorrhage by local treatment. The exact location of the bleeding area
      can be identified in actively bleeding noses with the fibreoptic naso
      laryngoscope and the bleeding arrested by chemical, or thermal cautery and in
      failed situations by using small nasal packs confined to the bleeding site. This
      approach to the management of posterior epistaxis is effective and reduces the
      duration of hospital stay. It significantly reduces the discomfort to the
      patient. The current practice of indiscriminate blind nasal packing in the hope
      of arresting nasal haemorrhage by incidental pressure on the bleeding site should
      be re-evaluated.

PMID- 1999662
TI  - Attachment of bacteria to tonsillar epithelium during acute tonsillitis.
AB  - Epithelial cells were scraped from the tonsillar surfaces of 15 patients with
      current acute tonsillitis (AT) and of 15 individually matched healthy persons.
      The cellular mixture was stained with acridine orange and bacteria seen to be
      attached to the epithelial cells under the fluorescent microscope were
      calculated. Conventional bacterial culturing was also performed simultaneously.
      Significantly more bacteria were attached to epithelial cells from the AT group
      than from the controls (greater than 10 attached bacteria per cell p = 0.0103,
      greater than 50 attached bacteria per cell p = 0.0212). In vivo determination of
      bacteria attached to epithelial cells offers prospects of gaining a better
      understanding of the aetiopathogenesis of acute tonsillitis.

PMID- 1999663
TI  - The hayfork: an aid to safer tonsillectomy.

PMID- 1999664
TI  - Modifying the translabyrinthine approach to preserve hearing during acoustic
      tumour surgery.
AB  - Removing an acoustic schwannoma using the translabyrinthine approach has
      previously been considered incompatible with hearing preservation. By modifying
      the approach and preventing the loss of endolymph, we have successfully removed
      an intracanalicular acoustic schwannoma, which originated from the inferior
      vestibular nerve, and preserved hearing in the operated ear. This report
      represents the preliminary findings using this particular technique in the
      management of an intracanalicular acoustic tumour.

PMID- 1999665
TI  - Unusual presentation of squamous cell carcinoma of the middle ear and mastoid.
AB  - An unusual case of squamous cell carcinoma of the middle ear and mastoid in which
      syncope was a major presenting feature is reported. No such case has been
      reported in the literature. A possible explanation is offered.

PMID- 1999666
TI  - Radiation-induced cranial nerve palsy: hypoglossal nerve and vocal cord palsies.
AB  - Cranial nerve palsies are an unexpected complication of radiotherapy for head and
      neck tumours. We present a case of this radiation-induced cranial palsy. An 18
      year-old female with nasopharyngeal carcinoma developed a right hypoglossal nerve
      palsy 42 months after cancericidal doses of radiotherapy. In addition, she
      developed a bilateral vocal cord palsy 62 months after therapy. Follow-up over
      four years has demonstrated no evidence of tumour recurrence and no sign of
      neurological improvement.

PMID- 1999667
TI  - An unusual treatment for a rare dilemma (oesophageal foreign body)
AB  - Identification of an intramural oesophageal fishbone at operation is difficult.
      Such a case is discussed with an attempted accurate radiological localization of
      site pre-operatively. No such case has so far been reported.

PMID- 1999668
TI  - Corrosion and fracture of a silver tracheostomy tube.
AB  - A sterling silver tracheostomy tube broke in use resulting in the death of a
      child. The nature of the fracture in the brazed joint is described, and corrosion
      identified as the mechanism of degradation of the joint. The corrosion is due
      either to exposure to body fluids over a long period, or to the use of
      hypochlorite solutions for cleaning and disinfection. The silver braze used had
      inferior corrosion resistance. It is recommended that appropriate grades of
      silver brazing alloy be used in the future, and that the mechanical integrity of
      medical devices joined with silver braze be regularly checked to anticipate
      failure in use.

PMID- 1999669
TI  - Massive metastasis from squamous carcinoma of the tonsil.
AB  - Squamous carcinomas of the oro-pharynx are associated with a high incidence of
      distant metastases at post-mortem. A case of a massive distant metastasis from a
      squamous cell carcinoma of the tonsil is presented. This occurred despite
      excellent local control. The pathology and the possible management implications
      are discussed.

PMID- 1999670
TI  - Diathermy haemostasis at tonsillectomy.

PMID- 1999671
TI  - Growth of mouse endometrial luminal epithelial cells in vitro: functional
      integrity of the oestrogen receptor system and failure of oestrogen to induce
      proliferation.
AB  - Normal endometrial luminal epithelial cells isolated from ovariectomized
      approximately 40-day-old BALB/cCrgl mice were purified by Percoll density
      gradient centrifugation and grown as primary cultures in collagen gel matrix and
      serum-free medium. Cells increased threefold in number during the 9-day culture
      period. Deletion of insulin, epidermal growth factor or bovine serum albumin
      resulted in decreased growth. Addition of any single factor to the unsupplemented
      medium had no effect. Relatively high levels of cytosolic oestrogen receptors and
      progestin receptors were demonstrable in the cultures. Addition of oestrogen did
      not enhance epithelial cell proliferation. On the contrary, all doses of
      oestrogen (180 fmol/l to 218 nmol/l) were inhibitory. Continuous exposure to
      oestradiol-17 beta (1.8 nmol/l) for 9 days in serum-free medium resulted in a
      decrease in cytosolic oestrogen receptors with an associated nuclear accumulation
      of oestrogen receptors. A corresponding increase in cytosolic progestin receptors
      was also observed, indicating that no qualitative modification of the oestrogen
      receptor system had occurred. Thus, as previously reported for vaginal epithelial
      cells, oestrogen, despite its stimulation of specific product synthesis
      (progestin receptors), did not increase proliferation of endometrial luminal
      epithelial cells in this culture system.

PMID- 1999672
TI  - Characterization of a factor(s) from partially purified human gonadotrophin
      preparations which inhibit(s) the binding of radiolabelled human LH and human
      chorionic gonadotrophin to Candida albicans.
AB  - We have shown previously that partially purified human chorionic gonadotrophin
      (hCG) preparations inhibited the specific binding of 125I-labelled hLH or hCG to
      Candida albicans membranes at much lower concentrations than did highly purified
      hLH or hCG preparations. We now describe the characterization and partial
      purification of a heat-labile glycoprotein from commercially available
      gonadotrophin preparations. The factor strongly inhibited LH binding to Candida
      membranes, but not to sheep or pig luteal LH receptors. This material had a
      molecular weight of 16,000-21,000 daltons, bound strongly to CM-Sepharose at
      physiological pH, and could be resolved completely from hCG and from epidermal
      growth factor-like factors present in commercial gonadotrophin preparations. Its
      activity was not attenuated by a range of inhibitors specific for the four major
      classes of proteolytic enzymes, nor did it inhibit hormone binding by causing
      degradation of 125I-labelled hLH or hCG tracers. Factors which inhibited hLH
      binding to Candida membranes were also present in partially purified human
      urinary and equine serum gonadotrophin preparations and in placental extracts,
      but were not detected in highly purified CG of hLH preparations. The properties
      of this factor were similar to those described for beta-core protein, a cleavage
      product of the beta subunit of hCG which is a contaminant of commercial
      gonadotrophin preparations. Highly purified beta-core protein inhibited 125I
      labelled hLH binding to Candida membranes, but not to sheep luteal binding sites.
      Preparations of hCG depleted of inhibitor activity could stimulate adenylate
      cyclase activity in Candida membranes almost five fold. In contrast, partially
      purified inhibitor preparations strongly inhibited basal adenylate cyclase
      activity (to 18% of control levels). These observations suggest that endogenous
      LH-like factors, perhaps similar to beta-core proteins of hCG, may play a role in
      the regulation of morphogenesis in Candida species.

PMID- 1999673
TI  - Parathyroid hormone-related protein in milk and its correlation with bovine milk
      calcium.
AB  - Parathyroid hormone-related protein (PTHrP) has been shown to be present in milk
      of various mammals. We have assayed PTHrP in milk of various species by
      radioimmunoassay and estimated the molecular weights by Western blot analysis.
      PTHrP concentrations in bovine, ovine and human milk were 59.2 +/- 18.5, 74.1 +/-
      35.0 and 36.6 +/- 20.7 micrograms/l (mean +/- S.D.) respectively, in pooled
      samples collected at various stages of lactation. PTHrP in mammalian milk was
      found to exist in two forms with molecular weights of 17.5 kDa and 21.5 kDa
      approximating those of PTHrP(1-108) and (1-141) respectively. In comparison,
      marsupial milk PTHrP appeared as a single low molecular weight form of 14.4 kDa
      which approximated to that of PTHrP(1-84). We performed a longitudinal study
      measuring the concentration of PTHrP in milk throughout lactation in cows, and
      found it to increase with the duration of lactation (r = 0.669, n = 91). We
      further examined the relationship between the concentration of PTHrP and total
      calcium in bovine milk, and the differences between these constituents in milk
      from Friesian and Jersey cows. PTHrP concentrations correlated positively with
      total milk calcium (r = 0.346, n = 105). The mean milk concentration of PTHrP of
      the Jerseys was significantly higher than that of the Friesians (52.6 +/- 5.4
      micrograms/l compared with 41.0 +/- 4.8 micrograms/l, P less than 0.01), as was
      the mean milk calcium concentration (30.5 +/- 3.0 mmol/l compared with 26.7 +/-
      2.7 mmol/l, P less than 0.01). We therefore postulate that production of PTHrP by
      the mammary gland may be associated with calcium transport from blood to milk.
      Also PTHrP may play a role in the development of milk fever in Jerseys which are
      predisposed to this condition.

PMID- 1999674
TI  - Indirect evidence for short-loop negative feedback of insulin secretion in the
      rat.
AB  - Feedback inhibition of glucose-mediated insulin release has repeatedly been
      demonstrated in isolated pancreatic islets and in the perfused pancreas. It was
      the aim of the present study to determine whether inhibition occurs through a
      long-loop (plasma concentration of insulin) or a short-loop (local concentration)
      action of insulin. The perfused rat pancreas was used, with different perfusion
      rates and different insulin concentrations in the medium. Increasing the flow
      rate from 1 to either 3 or 6 ml/min gradually decreased the insulin concentration
      in the effluent, at stimulatory concentrations of glucose (11.1 and 16.7 mmol/l).
      Under the same conditions, however, the integrated amount of insulin released
      over a period of 30 min was significantly enhanced. When exogenous insulin (2.7
      and 5.4 mumol/l) was added to the perfusion medium, insulin secretion in the
      presence of 11.1 or 16.7 mmol glucose/l at flow rates of 3 and 6 ml/min was
      diminished. This effect was most prominent with 11.1 mmol glucose/l and 2.7 mumol
      exogenous insulin/l at all flow rates (except 1 ml/min), as well as at the high
      perfusion flow rates with other glucose concentrations. Insulin secretion was not
      affected by 5.4 mumol exogenous insulin/l at 1 ml/min or by 2.7 mumol exogenous
      insulin/l at 3 ml/min. The data support a negative feedback inhibition of insulin
      secretion by secreted insulin, since insulin secretion was decreased by either
      adding exogenous insulin or by lowering endogenous insulin as the consequence of
      increased flow rates.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1999675
TI  - A renin-like enzyme in rat luteal tissue: evidence of local synthesis and its
      regulation during pregnancy.
AB  - Changes in the concentration of a renin-like enzyme were studied in androgenized
      rats in which a single luteal phase was induced by the administration of
      chorionic gonadotrophin. A significant increase in the luteal renin-like enzyme
      (RLE) concentration was found between the youngest corpora lutea (48 h old) and
      the oldest one studied (6 days old). The luteal RLE content varied independently
      of changes in plasma renin concentration. These results suggest that this enzyme
      was produced locally. The lack of correlation between the luteal RLE and plasma
      prolactin supports our previous observation that the changes in luteal renin
      concentration appear not to be prolactin-dependent. Furthermore, the suckling
      associated hormones appear not to be related with the regulation of luteal RLE
      concentration, since the values were not modified in androgenized maternal rats
      which were suckling when compared with the controls. Changes in luteal renin
      concentration were also studied during pregnancy. A significant increase was
      found a few hours after a fertile mating which reached a peak on day 1 of
      pregnancy, followed by a rapid decrease to low levels throughout the remainder of
      the pregnancy. Because the renin-angiotensin facilitates angiogenesis, luteal
      renin may act as an angiogenic factor, stimulating blood vessel growth in the
      corpora lutea. An alternative hypothesis is that the increase in RLE could be a
      trigger for calcium flux redistribution and steroid biosynthesis.

PMID- 1999676
TI  - Long-term iodination of thyroglobulin by porcine thyroid cells cultured in porous
      bottomed culture chambers: regulation by thyrotrophin.
AB  - Thyroid cells cultured as monolayers on the porous bottom of culture chambers
      have been shown to express some specific functions of thyroid follicles. This
      system, which allows independent access to apical and basal media, is suitable
      for the long-term study of polarized processes, as the cells maintain their
      polarized organization. Iodination of thyroglobulin has been investigated under
      different culture conditions in the presence or absence of TSH. Apical
      thyroglobulin accumulation, apical iodide concentration and thyroglobulin
      iodination have been followed simultaneously. Iodide (0.5 mumol/l) was added to
      basal medium at various stages: only once for 4-day incubations and at each
      medium change or daily for longer experiments. TSH increased the amount of
      thyroglobulin secreted into the apical medium by five- to sixfold, whereas high
      basal iodide concentrations (greater than 5 mumol/l) inhibited thyroglobulin
      secretion by TSH-stimulated cells. TSH increased iodide uptake giving an iodide
      concentration ratio between apical and basal media of about 5. Thyroglobulin
      iodination was dependent upon TSH. Thyroglobulin was iodinated only in the apical
      compartment. Secretion and iodination of thyroglobulin were polarized phenomena,
      but the polarity of iodination was total whereas the polarity of secretion was
      only partial (10% basal secretion). This functional asymmetry was maintained for
      up to 29 days. The maximal incorporation of iodine into thyroglobulin obtained
      was never higher than 3.5 atoms/mol. Apical iodide concentrations from 1 to 15
      mumol/l, depending on culture conditions, did not increase this value. These
      results suggest that cells cultured in this culture system are able to reproduce
      several steps of thyroidal iodide metabolism although there may be unknown
      factors which could interfere and reduce the efficiency of thyroglobulin
      iodination.

PMID- 1999677
TI  - Melatonin and the human gonadotrophin-releasing hormone pulse generator.

PMID- 1999678
TI  - Age-related alterations in the response of hepatic lipogenic enzymes to altered
      thyroid states in the rat.
AB  - To determine the age-related alterations in tissue-responsiveness to thyroid
      hormone action, the mRNA levels and the enzyme activities of hepatic cytosolic
      malate dehydrogenase (ME) and mitochondrial alpha-glycerophosphate dehydrogenase
      (alpha-GPD) were determined in groups of euthyroid, hypothyroid and hyperthyroid
      male Fischer 344 rats at various ages. The basal alpha-GPD level (change in
      optical density/min per mg) in 2-month-old rats (0.163 +/- 0.003) (S.E.M.) was
      significantly (P less than 0.001) higher than that in 6-month-old and 26-month
      old rats (0.116 +/- 0.012 and 0.098 +/- 0.013 respectively). The basal ME
      activity (mU/mg) was significantly (P less than 0.001) reduced in aged rats (9.2
      +/- 0.89) compared with younger rats (54.2 +/- 3.4 and 17.1 +/- 2.3 for 2-month
      old and 6-month-old rats respectively). The response of ME to tri-iodothyronine
      (T3) in aged rats compared with young rats was reduced approximately 50%. This
      age-related reduction in ME response to T3 could not be attributed to reduced
      food intake with ageing. Northern blot analysis showed that ME mRNA levels in
      hyperthyroid aged rats were 50% of those of young hyperthyroid rats. There were
      no significant differences in either basal or T3-stimulated alpha-GPD mRNA
      levels. The proportional reduction in steady-state ME mRNA levels and ME activity
      in aged rats indicates that this age-related change is modulated at a
      pretranslational level.

PMID- 1999679
TI  - Distribution of 125I-labelled insulin-binding sites in peripheral tissues of the
      normal and diabetic rat: an autoradiographic study.
AB  - In-vitro autoradiography was used to demonstrate the regional distribution of 12I
      labelled insulin-binding sites in the liver, kidney and heart of normal rats and
      rats made diabetic with streptozotocin. The distribution of insulin-binding sites
      in the liver of control rats was uniformly high, while in the kidney of control
      rats there was weak 125I-labelled insulin binding in the medulla and dense
      binding in the cortex. In the hearts of control rats a high density of 125I
      labelled insulin-binding sites was evident both in the atrial and ventricular
      muscle. Non-ketotic diabetes mellitus caused a marked increase in 125I-labelled
      insulin-binding sites in both the liver and kidney with the former tissue
      exhibiting a time-dependent (7 to 62 days) increase. There was no apparent effect
      of diabetes on insulin-binding sites in the heart. Since experimental diabetes
      causes (1) a decrease in circulating insulin concentration and (2) impaired
      insulin action at many target tissues, the increase in 125I-labelled insulin
      binding sites observed in the present study may represent a compensatory 'up
      regulation' of insulin receptors.

PMID- 1999680
TI  - Effects of full-length and truncated insulin-like growth factor-I on nitrogen
      balance and muscle protein metabolism in nitrogen-restricted rats.
AB  - The ability of insulin-like growth factor-I (IGF-I) to protect against losses of
      body protein during periods of dietary nitrogen restriction has been evaluated in
      young rats. Recombinant human IGF-I was administered by osmotic pumps at dose
      rates of 0, 1.2 or 2.9 mg/kg per day over a 7-day period beginning with the
      transfer of animals from an 18% to a 4% protein diet. A fourth group received the
      potent truncated IGF-I analogue, des(1-3)IGF-I, at a dose of 1.2 mg/kg per day
      over a comparable 7-day period. Plasma IGF-I levels were reduced by 60% following
      nitrogen restriction, a reduction that was partly prevented by IGF-I
      administration, especially at the higher dose, but not measurably by des(1-3)IGF
      I. The major IGF-binding protein circulating in blood, IGFBP-3, demonstrated a
      similar pattern of change. A significant (P less than 0.05) protection of body
      weight was achieved in the low dose IGF-I and des(1-3)IGF-I groups, but only
      after differences in food intake had been eliminated by analysis of covariance.
      Nitrogen balances were not significantly different unless analysis of covariance
      was used to adjust for the nitrogen intakes, whereupon all treatment groups
      showed improved balance, especially the animals treated with the low IGF-I dose
      and des(1-3)IGF-I (both P less than 0.01). The rate of muscle protein breakdown
      calculated from the urinary excretion of 3-methyl-histidine was not significantly
      altered by the treatments, but fell progressively throughout the 7 days. The
      fractional rate of muscle protein synthesis measured on the final day was
      increased by 31,26 and 21% respectively by the low and high doses of IGF-I and by
      des(1-3)IGF-I. Organ weights (g/kg body weight) showed no effects of IGF-I
      treatment except for 16% increases in the weight of kidneys in the high dose IGF
      I and the des(1-3)IGF-I groups. Carcass analyses demonstrated higher water and
      lower fat contents (all P less than 0.01) in the same groups. These results
      suggest that exogenous IGF-I and especially des(1-3)IGF-I can partly protect body
      protein reserves during nitrogen restriction.

PMID- 1999681
TI  - Effect modification and the limits of biological inference from epidemiologic
      data.

PMID- 1999682
TI  - Characteristics of respondents and nonrespondents in a prospective study of
      osteoporosis.
AB  - During 1981-1982, a cohort of elderly Japanese Americans living in Hawaii was
      recruited for an epidemiologic study of osteoporosis. The male subjects were
      simultaneously being examined for an epidemiologic study of heart disease.
      Baseline data collected from both the men and women at a previous heart disease
      examination were used to compare responders vs nonresponders. The target
      population for the osteoporosis study consisted of 1685 men and 1594 women. Of
      these, 1379 men (81.8%) and 1105 women (72.0%) participated in the initial
      osteoporosis examination. For each sex, nonrespondents were older and had higher
      systolic blood pressure levels than did the respondents. Male nonresponders had a
      higher stroke prevalence and more frequent recent use of vasodilator medicine.
      Female nonresponders had a less frequent history of having ever taken female
      hormones than did the responders. The responders and nonresponders were
      reasonably similar in other respects, as indicated by the comparison of more than
      40 other variables. This suggests that nonresponse bias is probably not a major
      influence in exposure-disease associations in this osteoporosis cohort. We
      believe this is the first published report dealing with nonresponse
      characteristics in a cohort study of osteoporosis.

PMID- 1999683
TI  - Binary methods for continuous outcomes: a parametric alternative.
AB  - Often a "disease" or "state of disease" is defined by a subdomain of a continuous
      outcome variable. For example, the subdomain of diastolic blood pressure greater
      than 90 mmHg has been used to define hypertension. The classical method of
      estimating the risk (or prevalence) of such defined disease states is to
      dichotomize the outcome variable according to the cutoff value. The standard
      statistical analysis of such risk of disease then exploits methods developed
      specifically for binary data, usually based on the binomial distribution. We
      present a method, based on the assumption of a Gaussian (normal) distribution for
      the continuous outcome, which does not resort to dichotomization. Specifically,
      the estimation of risk and its variance is presented for the one- and two-sample
      situations, with the latter focusing on risk differences and ratios, and odds
      ratios. The binomial approach applied to the dichotomized data is found to be
      less efficient than the proposed method by 67% or less. The latter is found to be
      very accurate, even for small sample sizes, although rather sensitive to
      substitutions of the underlying distribution by thicker tailed distributions.
      Canadian total cholesterol data are used to illustrate the problem. For the one
      sample case, the approach is illustrated using data from a study of the arterial
      oxygenation of 20 patients during one-lung anesthesia for thoracic surgery. For
      the two-sample case, data from a prognostic study of the renal function of 87
      lupus nephritic patients are used.

PMID- 1999684
TI  - Case finding, data quality aspects and comparability of myocardial infarction
      registers: results of a south German register study.
AB  - The population-based Augsburg Coronary Event Register (330,000 residents, age 25
      74 years) has registered a total of 1012 cases of acute myocardial infarction
      (AMI) in 1985 and 1021 AMI in 1986 and categorized them on the basis of the
      current WHO diagnostic algorithm for AMI. The register is designed for
      longitudinal comparisons of annual AMI risk (incidence, attack rate, death rate),
      and the risk to the AMI patients themselves (28-day case fatality). The
      methodology and specific issues encountered during registration and data
      evaluation are described. With an estimated 95% completeness of case finding, the
      quality control data review which the register conducts annually shows a
      consistency of specific data structures which indicate stable case finding and
      validation procedures. However, local conditions which affect case finding and
      data completeness per case are responsible for the creation of subsets of AMI
      which are in turn distinguished by differences in diagnostic category structures.
      With regard to the study objectives, the differences among subsets appear to have
      the least effect on rate calculations if DEFINITE and POSSIBLE AMI are combined.
      The implications of methodological variations and subset differences within and
      across registers on annual rate calculations and result comparisons are
      discussed.

PMID- 1999685
TI  - The history of nitrite in human nutrition: a contribution from German cookery
      books.
AB  - In order to settle the question of when saltpetre (nitrate) came in use as an
      additive to human food, a number of historic cookery books from Germany and
      Austria were reviewed. Obviously, the change from vegetable dyes to saltpetre for
      the coloring or color preservation, respectively, of meat occurred between 1600
      and 1750, probably near 1700. The addition of sugar which favours the reduction
      of nitrate to the active agent nitrite became common practice during the 19th
      century. Thus some historic parallels to the appearance of colorectal cancer,
      multiple sclerosis and rheumatoid arthritis in the medical literature became
      apparent.

PMID- 1999686
TI  - Sequential or fixed sample trial design? A case study by stochastic simulation.
AB  - The properties of Wilcoxon's rank sum test for fixed sample size and a Wilcoxon
      type two-sample sequential test have been illustrated and compared by means of
      stochastic simulation. Data from a real fixed sample trial have been used, both
      for resampling from the original data, and for construction of an idealized
      theoretical distribution. The sequential and the fixed sample test obtain equal
      power, but the sequential test mostly includes considerably fewer patients to
      reach a conclusion, i.e. the mean and median number of patients included are both
      much lower than the fixed sample size. Under the hypotheses only a small fraction
      of the simulation runs exceed the fixed sample size. These findings exemplify
      results obtained in theoretical analyses and simulation studies covering a wide
      range of distributions. In our opinion sequential tests have obvious advantages
      and are in many cases better alternatives than fixed sample tests in clinical
      trials.

PMID- 1999687
TI  - The effect of beta-carotene on the regression and progression of cervical
      dysplasia: a clinical experiment.
AB  - In order to gain insight into the causality of the relation between beta-carotene
      and cancer, we performed a randomized placebo-controlled trial in which the
      effect of beta-carotene on the regression and progression rates of cervical
      dysplasia were examined. The experimental group (n = 137) received a supplemental
      dose of 10 mg of beta-carotene daily for 3 months. The control group (n = 141)
      received placebo capsules. As the outcome parameter, two definitions of
      regression and progression were used, which were based on the degree of dysplasia
      before and after the medication period. The number of patients who showed
      progression was too small to allow conclusions. No effect of beta-carotene on the
      regression percentages was observed: OR = 0.68 (95% CI: 0.28-1.60) using the
      broad definition; and OR = 1.22 (95% CI: 0.43-3.41) with the strict definition. A
      secondary analysis, in which the effect of the total intake of beta-carotene
      (diet + medication) on the regression percentages of cervical dysplasia was
      studied, did not show a positive effect either. The paper discusses to what
      extent issues in the study design may have masked a potential effect and how our
      results affect the evidence for a causal relation between beta-carotene and
      cancer.

PMID- 1999688
TI  - Systematic computer-aided search of optimal staging system for colorectal cancer.
AB  - Two hundred and ninety-eight patients with curatively resected colorectal cancer
      were classified into 12 categories according to the depth of tumour penetration
      (T1-T4), and lymph node status (N0-N2). Using a computer, these categories were
      grouped into 2-12 stages in every possible combination, so a total of 146,975
      logical classifications were generated. The optimal model was selected for each
      group of classifications with equal stage number, thus giving the greatest
      prognostic information on 5-year survival according to the Akaike criterion. The
      results showed that (1) 13% of the total classifications, including 85% of the 3
      stage classifications, were better than the Dukes system in predicting our
      patients' outcomes; (2) the T-level was a stage-determinant even more important
      than the N-level; and (3) major changes in prognosis occurred at more advanced
      stages than the classical "turning points". We conclude that in order to find an
      optimal staging of cancer, systematic computer-aided search through all the
      possible classifications is necessary, using the appropriate database.

PMID- 1999689
TI  - The community hospital-based stroke programs in North Carolina, Oregon and New
      York--V. Stroke diagnosis: factors influencing the diagnostic evaluation of
      patients following acute stroke.
AB  - Among the 4129 patients of the Community Hospital-based Stroke Program, 30% had
      an unspecified stroke diagnosis. Since specific diagnosis and, perhaps, eventual
      treatment, derives in part from diagnostic testing, we examined the effect of
      clinical condition, geographic and demographic factors on the incidence of
      certain diagnostic tests after acute stroke. In this multivariable analysis,
      race, sex, history of hypertension and history of diabetes did not influence the
      chance of having any test, but older age strongly reduced the chances of
      receiving extensive evaluation. When CT scanning was available, the utilization
      of a CT as well as other diagnostic studies including cerebral angiography,
      radionuclide brain scan, EEG and EKG was increased. The odds of receiving a CT
      scan increased if the patient was married, and decreased with a history of
      previous stroke. A history of previous TIA increased the chance of having a
      cerebral angiogram while a history of cardiac disease decreased the chance. There
      were striking regional geographic differences in the use of CT, radionuclide
      brain scanning and cerebral angiography which may, in part, reflect differences
      between the availability of these technologies in urban and rural hospitals.
      These results indicate that evaluation of stroke patients remains heterogenous.

PMID- 1999690
TI  - Psychiatric and physical illness, sociodemographic characteristics, and the use
      of psychotropic drugs in the community: results from the Upper Bavarian Field
      Study.
AB  - In the Upper Bavarian Field Study a total of 1536 persons (15 years and older)
      were interviewed by research psychiatrists. 8.1% of all respondents took a
      psychotropic drug during the 7 days prior to the interview. The consumption rate
      among women was about three times as high as that for men. The use of
      psychotropic drugs increased with age. No consistent pattern was found with
      respect to social class. According to psychiatric/physical health status the
      highest consumption rate (29.4%) was found among those suffering solely from
      psychiatric disorders. The simultaneous occurrence of both psychiatric and
      physical disorder did not increase the risk of drug taking (21.4%). Less than 5%
      of the healthy respondents and of those suffering solely from a physical disorder
      used psychotropic drugs. A large proportion (63.0%) of those with previous
      psychiatric in- and outpatient treatment received psychotropic medication, as
      well as those suffering from schizophrenia (66.7%), affective psychoses (52.6%)
      and anxiety disorders (50.0%). The higher consumption of psychotropic drugs among
      women could not be explained by higher psychiatric or physical morbidity or the
      fact that women consult primary care physicians more frequently than do men.
      Controlling for co-morbidity and annual consultation of family physicians,
      significant sex differences in the consumption of psychotropic drugs persist.

PMID- 1999691
TI  - Increased incidence of diabetes mellitus in relation to abdominal adiposity in
      older women.
AB  - The relationship between body fat distribution, measured by the ratio of waist-to
      hip circumferences (WHR), and the 2 year incidence of diabetes mellitus was
      examined in a cohort of 41,837 women aged 55-69 years. The 399 women who reported
      the new onset of diabetes had a significantly greater mean body mass index
      (kg/m2) and WHR than non-cases. After adjustment for body mass index (BMI), age
      and education level using multivariate logistic regression, WHR was a significant
      independent predictor of diabetes in a dose-response fashion. Cases were 4.6
      times (95% CI = 3.8, 5.6) more likely than non-cases to be in the upper tertile
      of WHR and 2.2 times (95% CI = 1.8, 2.7) more likely to be in the middle tertile.
      Women in the highest tertiles of both WHR and BMI had a 14.4-fold (95% CI = 9.5,
      21.9) higher risk of diabetes than women in the lowest tertiles. These results
      demonstrate that increased abdominal adiposity is a significant independent risk
      factor for the development of diabetes mellitus in older women.

PMID- 1999692
TI  - Umbrellas and lions.

PMID- 1999693
TI  - In vitro evaluation of relative perforating potential of central venous
      catheters: comparison of materials, selected models, number of lumens, and angles
      of incidence to simulated membrane.
AB  - Perforation of the vena cava or atrium is a serious complication of monitoring
      with a central venous catheter. We designed an in vitro model with a pulsating
      simulated membrane to evaluate a number of variables that could affect relative
      perforating potential of different types of central venous catheters. To
      determine the perforating potential of central venous catheters, we studied the
      effects of (1) the angle of incidence (n = 6) between catheter and simulated
      membrane; (2) catheter material (polyurethane and polyethylene); (3) make
      (manufacturer and model) (n = 6), with 3 catheters of each make tested; (4)
      design (n = 3 each: silicone rubber, open-ended, blunt-ended, and polyurethane
      pigtail); and (5) number of lumens (single, double, or triple). Each trial was
      repeated five times with each catheter that was tested. Perforation was
      significantly more likely when the angle of incidence between catheter and
      pulsating simulated membrane was greater than 40 degrees than when it was 40
      degrees (P less than 0.05). Perforation was less likely with single-lumen than
      comparable French-sized double- and triple-lumen catheters; among single-lumen
      catheters, perforation required many more pulsations with a polyurethane than a
      polyethylene catheter (P less than 0.001). Perforation potential differed
      significantly among 6 makes of 7-French triple-lumen catheters (P less than
      0.05). Compared with other materials or designs, silicone rubber or a pigtail tip
      decreased the perforation potential of catheters (P less than 0.001). These data
      offer additional objective information to consider when choosing and positioning
      central venous catheters.

PMID- 1999694
TI  - The relative accuracies of two automated noninvasive arterial pressure
      measurement devices.
AB  - We compared the accuracies of two types of noninvasive blood pressure devices.
      Thirty-two patients requiring an intraarterial catheter for anesthetic management
      underwent simultaneous monitoring with Dinamap 1846SX and Ohmeda Finapres 3700
      devices. For the first 10 minutes of recording, new Dinamap determinations were
      performed every 60 seconds; subsequent recordings were made at 3-minute
      intervals. Data were obtained at the time of new Dinamap readings, and twice
      between new readings to approximate the real-time performance of the two
      monitors. We defined superior accuracy as a statistically significant difference
      in mean absolute error greater than 5 mm Hg. With these criteria, pooled data
      from all patients revealed no difference in performance, even in real time.
      Pooled data can be misleading since there was a significant amount of variation
      in accuracy for both monitors. Therefore, we used nonparametric analysis to
      determine how many individual patients were monitored better by either device.
      When we compared only data from new Dinamap readings, the Finapres monitor showed
      superior performance for systolic readings in 13 patients, versus 6 patients for
      the Dinamap (P less than 0.05, chi-square test). Similar analysis for diastolic
      and mean pressure performance did not reach statistical significance. However, in
      real time, the Finapres unit monitored more patients more accurately for systolic
      (14 Finapres versus 3 Dinamap), diastolic (11 Finapres versus 3 Dinamap), and
      mean (10 Finapres versus 3 Dinamap) pressure determinations. The magnitude of
      these differences were, however, less dramatic than expected. This was probably
      due to stabilization of arterial pressure during the anesthetic, which minimized
      the error due to intermittent sampling. We conclude that continuous Finapres
      readings and new Dinamap determinations are equally accurate for diastolic and
      mean arterial pressures. The accuracy of Finapres appears to be slightly superior
      for systolic pressure. The intermittent sampling of oscillometric devices
      compromises their performance relative to the Finapres in many, but not all,
      cases.

PMID- 1999695
TI  - Electroencephalographic mapping during isoflurane anesthesia for treatment of
      mental depression.
AB  - Seven patients undergoing isoflurane anesthesia were studied using
      electroencephalographic (EEG) mapping, a computer-assisted technique of EEG
      processing that permits the analysis of the spatial distribution of frequency
      components of the human EEG. After induction with thiopental, the patients were
      hyperventilated (carbon dioxide tension, 25 to 28 mm Hg) with 4% isoflurane in
      oxygen until a burst-suppression EEG appeared. Brain electrical activity was
      compared before anesthesia, at 0.5 to 0.8% and 1.8 to 2.1% isoflurane, during
      bursts, and after anesthesia. Starting from an alpha EEG with occipital
      predominance, a distinct alpha activation appeared over the whole cortex during
      0.5 to 0.8% isoflurane. Decreased alpha amplitude with a maximum over the
      frontotemporal regions was observed during 1.8 to 2.1% isoflurane. Bursts
      consisted of high amplitude in all frequency bands. In the delta and the theta
      bands, voltage was very low before isoflurane administration, and increased in
      relation to depth of anesthesia. A minimum in delta and theta amplitudes occurred
      over both central regions. The dominant frequency, defined as the frequency
      component with the highest amplitude in the frequency spectrum, decreased from 8
      to 4 and finally to 1 Hz, while its amplitude increased from 3 to 13 microV. As
      anesthesia deepened, the dominant frequency shifted from the occiput to the
      frontal cortex. Brain mapping transfers an immense amount of
      electroencephalographic (EEG) data into a comprehensive, easily readable image of
      brain function during anesthesia for therapy of mental depression. To make use of
      this technique in the operating room, further investigation and development
      toward on-line mapping are necessary.

PMID- 1999696
TI  - Usefulness of epidurally evoked cortical potential monitoring during
      cervicomedullary glioma surgery.
AB  - This report describes a patient with an intramedullary ependymoma at the region
      of the cervicomedullary junction in whom there was an abolition of somatosensory
      evoked potentials following median nerve stimulation. During intraoperative
      monitoring of cortical potentials elicited by epidural cervical cord stimulation,
      the tumor was removed. Posterior epidural stimulation appeared to depolarize more
      ascending fibers than did stimulation of a single peripheral nerve. We recommend
      that, in cases of operations in this vital area, epidurally evoked cortical
      potentials be monitored intraoperatively.

PMID- 1999697
TI  - Oxygen pipeline supply failure: a coping strategy.
AB  - Oxygen is the most vital drug administered during anesthesia. The delivery of
      hypoxic or even anoxic gas mixtures during anesthesia has been reported. Because
      such occurrences often meet with disaster, modern anesthesia machines have a
      system of alarms to warn against the delivery of hypoxic or anoxic gas mixtures
      and also to warn of the failure of the oxygen pipeline supply. We describe the
      occurrence of a sudden failure of the oxygen pipeline supply, and discuss a
      strategy for coping with this emergency.

PMID- 1999698
TI  - A target feedback device for ventilatory muscle training.
AB  - In a previous study, we successfully used a target feedback device, together with
      an external resistor, to train the ventilatory muscles of patients with chronic
      obstructive pulmonary disease. In this article, we describe the details of the
      design and function of the target feedback device. When used in conjunction with
      an external resistance, the target feedback device provides timing and pressure
      targets, together with feedback information, on whether these targets are
      achieved. The target feedback device consists of readily available electronic
      components and is relatively simple to construct. Adjustment of an external
      pressure knob permits setting of pressure targets. Adjustment of internal
      components is possible and allows control of breathing frequency, inspiratory
      time, and breathing waveform.

PMID- 1999700
TI  - Low perfusion pressure or interruption of blood flow suppresses
      electroencephalographic activity?

PMID- 1999699
TI  - Blood pressure monitoring: automated oscillometric devices.
AB  - An understanding of the principles of blood pressure measurement with automated
      oscillometric devices (e.g., Dinamap) allows a user to realize the purpose and
      level of accuracy for which the equipment is designed. Good technique cells for
      various actions: (1) using a cuff of proper size (too large a cuff will generally
      work acceptably, but too small a cuff will yield erroneously high readings); (2)
      squeezing all of the residual air out of the cuff before applying it to the arm
      or leg; (3) wrapping the cuff snugly around the arm or leg; (4) instructing the
      patient to refrain from talking or moving and letting nothing press against the
      cuff during measurement; (5) keeping the cuff and heart at the same horizontal
      level. (6) When instrument malfunction is suspected, first checking the status of
      the patient (not the status of the instrument) to be sure that a clinical
      emergency is not causing the suspected "malfunction"; (7) repeating a reading
      several times when it is suspicious and, if necessary, modifying the measurement
      conditions by using, for example, different limbs or different cuffs until the
      question is resolved; and (8) remembering that a leak in the cuff, hoses, or
      connection can cause an unexpected malfunction.

PMID- 1999701
TI  - Measurement of arterial oxygen tension in the hyperbaric environment.

PMID- 1999702
TI  - Skin reflectance pulse oximetry: in vivo measurements from the forearm and calf.
AB  - This study describes the results from a series of human experiments demonstrating
      the ability to measure arterial hemoglobin oxygen saturation (SaO2) from the
      forearm and calf using a reflectance pulse oximeter sensor. A special optical
      reflectance sensor that includes a heating element was interfaced to a
      temperature controller and a commercial Data-scope ACCUSAT pulse oximeter that
      was adapted for this study to perform as a reflectance pulse oximeter. The
      reflectance pulse oximeter sensor was evaluated in a group of 10 healthy adult
      volunteers during steady-state hypoxia. Hypoxia was induced by gradually lowering
      the inspired fraction of oxygen in the breathing gas mixture from 100 to 12%.
      Simultaneous SaO2 measurements obtained from the forearm and calf with two
      identical reflectance pulse oximeters were compared with SaO2 values measured by
      a finger sensor that was interfaced to a standard Datascope ACCUSAT transmittance
      pulse oximeter. The equations for the best-fitted linear regression lines between
      the percent reflectance, SpO2(r), and transmittance, SpO2(t), values in the range
      between 73 and 100% were SpO2(r) = -7.06 + 1.09 SpO2(t) for the forearm (n = 91,
      r = 0.95) and SpO2(r) = 7.78 + 0.93 SpO2(t) for the calf (n = 93, r = 0.88). The
      regression analysis of the forearm data revealed a mean +/- SD error of 2.47 +/-
      1.66% (SaO2 = 90-100%), 2.35 +/- 2.45% (SaO2 = 80-89%), and 2.42 +/- 1.20% (SaO2
      = 70-79%). The corresponding regression analysis of the calf data revealed a mean
      +/- SD error of 3.36 +/- 3.06% (SaO2 = 90-100%), 3.45 +/- 4.12% (SaO2 = 80-89%),
      and 2.97 +/- 2.75% (SaO2 = 70-79%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1999703
TI  - Computerization of anesthesia information management.

PMID- 1999704
TI  - Fluoropyrimidine biochemical modulation in colon cancer: pharmacology relevant in
      both the laboratory and the clinic.

PMID- 1999705
TI  - Why should the clonogenic cell assay be prognostically important in ovarian
      cancer?

PMID- 1999706
TI  - The influence of drug interval on the effect of methotrexate and fluorouracil in
      the treatment of advanced colorectal cancer.
AB  - The importance of the interval between methotrexate (MTX) and fluorouracil (5-FU)
      was studied in 168 patients with previously untreated, measurable, advanced
      colorectal cancer. They were randomized to receive MTX 200 mg/m2, followed by 5
      FU 600 mg/m2 either 24 hours (arm A) or 1 hour (arm B) after MTX. All patients
      received leucovorin (LV) 24 hours after MTX, 10 mg/m2 orally every 6 hours for
      six doses. The regimen was repeated every 2 weeks, with 5-FU escalation as
      tolerated. Arm A was significantly better than arm B with respect to overall
      response rate (29% v 14.5%, P = .026), time to progression (TTP; median, 9.9
      months v 5.9 months, P = .009), and survival (median, 15.3 months v 11.4 months,
      P = .003). Significant differences between arms were not found in response rate,
      median TTP, or median survival for the subgroup of patients with rectal primaries
      who comprised 20% of the patients in each arm. Significant factors prognostic for
      survival were performance status and number of metastases, as well as treatment.
      Age did not influence survival. Toxicity was similar in both arms and was
      primarily gastrointestinal. More mucositis was seen in arm A. There were four
      toxic deaths secondary to neutropenia and infection (one from arm A and three
      from arm B) and three other deaths (two from arm A and one from arm B) that were
      possibly drug-related. The combination of MTX with LV rescue and 5-FU is an
      active regimen in advanced colorectal cancer; its efficacy is increased in colon,
      but not rectal cancer, when the interval between MTX and 5-FU is long (24 hours)
      rather than short (1 hour).

PMID- 1999707
TI  - Clonogenic growth in vitro: an independent biologic prognostic factor in ovarian
      carcinoma.
AB  - A retrospective analysis was performed to investigate the prognostic value of
      growth in a human tumor clonogenic assay system for 84 ovarian cancer patients. A
      significant difference in survival probability (determined by the method of
      Kaplan-Meier) was found by univariate analysis between patients with ovarian
      carcinoma whose tumors manifested clonogenic growth (defined as growth of greater
      than or equal to five colonies per plate) and patients whose tumors did not grow.
      Clonogenic growth in vitro was associated with worse prognosis (P = .007, log
      rank test). A number of generally accepted prognostic factors, International
      Federation of Gynecology and Obstetrics (FIGO) stage (P = .003), residual tumor
      mass (P less than .001), and grade (P = .011), were also of prognostic importance
      in our patient population. Multivariate analysis, based on the Cox regression
      model, identified clonogenic growth as a significant independent prognostic
      parameter in ovarian carcinoma (P = .031), in addition to the conventional risk
      factors. Estimation of survival of individual patients was best accomplished by
      combining the factors of residual tumor mass (P less than .05), age (P less than
      .01), and clonogenic growth (P less than .05) (in sequence of decreasing
      potential of risk).

PMID- 1999708
TI  - Second-line platinum therapy in patients with ovarian cancer previously treated
      with cisplatin.
AB  - In an effort to critically define the incidence and clinical characteristics of
      secondary responses to cisplatin-based therapy in patients with ovarian cancer
      previously treated with a cisplatin-based program, a retrospective review was
      undertaken of patients at the Memorial Sloan-Kettering Cancer Center who received
      greater than or equal to two cisplatin/carboplatin-based programs. Eighty-two
      patients were identified who met the entry criteria of having had a cisplatin
      free interval (CFI) of more than 4 months between the completion of their first
      regimen and the institution of a second cisplatin/carboplatin program. Of the 72
      assessable patients (10 had no measurable disease, and a laparotomy was not
      performed to assess response), 31 (43%) responded, including 10 surgically
      defined complete responses (S-CRs). The overall response rates (and S-CR rate),
      based on duration of CFI, were 5 to 12 months, 27% (5%); 13 to 24 months, 33%
      (11%); and more than 24 months, 59% (22%). Twenty-nine patients (35%) received
      noncisplatin/carboplatin-containing treatments between the cisplatin programs.
      Patients without any treatment for more than 24 months from the completion of
      their initial therapy experienced a 77% (17 of 22) response rate and a 32% (seven
      of 22) S-CR rate. In conclusion, secondary responses to cisplatin/carboplatin
      based treatment are common in patients with ovarian cancer who have previously
      responded to the agents and increase in frequency with greater distance from the
      initial therapy.

PMID- 1999709
TI  - Human growth hormone and insulin-like growth factor-1 enhance the proliferation
      of human leukemic blasts.
AB  - As the number of long-term survivors of childhood leukemia increases, growth
      retardation has emerged as a significant complication. Treatment of these
      children with growth hormone (GH) has been suggested and sporadically
      implemented. We, therefore, studied the effect of human GH (hGH) and its by
      product insulin-like growth factor-1 (IGF-1) on the growth of leukemic cells in
      vitro. Under serum-free conditions hGH and IGF-1 induced a significant dose
      dependent proliferative effect on promyelocytic leukemia (HL60) and Burkitt's
      lymphoma (Daudi) cell lines. Anti-hGH antibodies negated the stimulatory effect
      of hGH and anti-IGF-1 serum abrogated the growth-promoting effect enhanced by IGF
      1. Similar statistically significant stimulatory properties were found when
      freshly obtained marrow cells from four of five acute lymphoblastic leukemia
      (ALL) of childhood and four acute myelogenous leukemia (AML) patients were
      studied in ALL and AML blast-cell clonogenic assays. ALL colonies increased
      numerically by 72% (P less than .025) and AML colonies by 92% (P less than .01)
      in the presence of hGH at concentrations of 2.5 x 10(2) and 3.0 x 10(2) ng/mL,
      respectively. IGF-1 stimulated ALL and AML blast-colony growth at concentrations
      ranging from 0.05 to 0.5 ng/mL by up to 105% (P less than .025) and 65% (P less
      than .03), respectively. Our in vitro data suggest that circulating hGH and IGF-1
      may promote leukemic blast cell replication in vivo, and the supplemental
      administration of hGH to leukemia patients in remission must be carefully
      monitored for early relapse.

PMID- 1999710
TI  - Abnormal growth patterns and adult short stature in 115 long-term survivors of
      childhood leukemia.
AB  - Significant growth retardation was found in 115 survivors of childhood acute
      lymphoblastic leukemia (ALL) who had completed their growth. These children were
      diagnosed before 12 years of age and treated on four protocols in a single
      institution; all received either cranial (n = 78) or craniospinal (n = 37)
      prophylactic irradiation. Patients' heights at diagnosis were within expected
      ranges, but final heights were greater than or equal to 1 SD below population
      means in 74% of cases and greater than or equal to 2 SD in 37%. Effects on growth
      were more pronounced for children who had received craniospinal irradiation, but
      decrements were also significant in the cranial irradiation group, with adult
      heights greater than or equal to 2 SD below population norms in 32%. Growth
      retardation was significantly greater (P less than .0001) in children who had
      earlier disease onset. Growth deceleration occurred not only during chemotherapy
      but during a later period that followed an interval of improved growth in many
      cases. Thus, late decrements in growth may be missed in studies that do not
      follow patients until they have attained final heights. These findings indicate
      that abnormally short stature among survivors of ALL merits further clinical and
      research attention.

PMID- 1999711
TI  - Treatment of relapsed non-Hodgkin's lymphomas with dexamethasone, high-dose
      cytarabine, and cisplatin before marrow transplantation.
AB  - Combination chemotherapy is capable of curing many patients with newly diagnosed
      intermediate- and high-grade non-Hodgkin's lymphomas (NHL), but treatment of
      relapsed NHL remains problematic. Bone marrow transplantation (BMT) offers the
      best chance for disease-free survival, but interim chemotherapy is often
      necessary while awaiting BMT, especially for patients with bulky disease. We
      report here 39 patients (median age, 44 years) who failed primary therapy with
      doxorubicin-based regimens and subsequently were treated with one to six cycles
      of dexamethasone, 40 mg intravenous (IV) every day on days 1 to 4, cisplatin 100
      mg/m2 by continuous infusion on day 1, and cytarabine 2 g/m2 IV every 12 hours x
      two doses on day 2 (DHAP) before the planned BMT. Histologies included 16 diffuse
      large-cell, six diffuse mixed, five diffuse small-cleaved, four lymphoblastic,
      and eight other. Twenty-eight patients had stage IV disease, 13 had B symptoms,
      and 20 had an elevated lactate dehydrogenase (LDH). Patients had been treated
      with a median of three previous chemotherapy regimens. Sixty-one percent of
      patients had high tumor burdens according to the MD Anderson criteria. Objective
      responses to DHAP were seen in 26 patients (67%) including nine complete
      responses (CRs) (23%) and 17 partial responses (PRs) (44%), and responses lasted
      a median of 7.5 months. Myelosuppression was the major toxicity, but there were
      no treatment-related deaths. To date, 17 patients have undergone subsequent BMT
      with a projected 3-year disease-free survival of 15%. We conclude that the DHAP
      regimen is effective short-term salvage therapy for relapsed NHL patients, but
      the long-term prognosis of multiply relapsed patients remains poor.

PMID- 1999712
TI  - Second primary cancer following Hodgkin's disease: updated results of an Italian
      multicentric study.
AB  - The risk of second primary cancer (SPC) was evaluated in 947 patients treated for
      Hodgkin's disease (HD) during the period January 1969 to December 1979. The
      median follow-up of this series was 10.5 years (range, 9 to 19). Treatment
      categories included radiotherapy (RT) alone (115 patients, 12%), chemotherapy
      (CHT) alone (161 patients, 17%), combined RT plus CHT (381 patients, 40%), and
      salvage treatment for resistant or relapsing HD (290 patients, 30.6%). Fifty-six
      SPCs were observed, occurring between 1 and 17 years from initial treatment.
      Among these, secondary acute nonlymphoid leukemia (s-ANLL) was the most frequent
      SPC (23 cases). Secondary non-Hodgkin's lymphoma (s-NHL) occurred in 5 patients,
      whereas a secondary solid tumor (s-ST) was observed in 28 patients. The
      calculated actuarial risk (+/- SE) of developing SPC was 5.0% (+/- 0.9%) and
      23.1% (+/- 5.8%) at 10 and 19 years, respectively. Concerning treatment
      modalities and s-ANLL risk, no cases were observed in the radiotherapy group,
      whereas CHT plus RT and salvage groups showed the highest actuarial risk. This
      was, in fact, at 10 and 19 years, 3.1% (+/- 0.9%) and 8.1% (+/- 4.0%) in the
      former group, and 1.8% (+/- 1.0%) and 16% (+/- 9.0%) in the latter. A
      statistically significant difference was observed when the CHT plus RT group was
      compared with CHT and RT groups (P = .04). Concerning the relationships with
      chemotherapeutic regimens, 12 s-ANLL cases occurred in the mechlorethamine,
      vincristine, procarbazine, and prednisone (MOPP) plus RT group, and only one case
      in the group receiving doxorubicin, bleomycin, vinblastine, and dacarbazine
      (ABVD) plus RT. A statistically significant difference of s-ANLL actuarial risk
      was found comparing patients receiving MOPP plus RT to all other treatment groups
      (P = .04). With respect to s-ST, the actuarial risk at 10 and 19 years was 2.0%
      (+/- 0.6%) and 13.0% (+/- 3.8%), respectively. No significant differences were
      found among groups treated with different modalities. These data were confirmed
      by a multivariate analysis, which indicated treatment modality and age as
      independent variables for s-ANLL and s-ST development, respectively. Based on the
      prolonged follow-up analysis, the actuarial SPC risk at 10 years hereby reported
      should reflect the real SPC incidence in our series.

PMID- 1999713
TI  - The pattern of intrathoracic Hodgkin's disease assessed by computed tomography.
AB  - Computed tomography (CT) was used to define the sites of intrathoracic
      abnormality in Hodgkin's disease, determine a pattern of progression of disease
      in the thorax, and establish the place of this pattern of spread in the
      differential diagnosis of thoracic abnormalities. One hundred eight patients with
      newly diagnosed Hodgkin's disease were studied by chest CT. Seventy-seven
      patients had intrathoracic abnormalities. The pattern seen was one of contiguous
      spread from the anterior mediastinal/paratracheal area to the other mediastinal
      lymph node groups (aortopulmonary, subcarinal, posterior mediastinal, and
      internal mammary), to the hila, and then into the lung by extension or as
      discrete nodules. Involvement of the pleura, pericardium, or chest wall occurred
      only after the anterior mediastinal/paratracheal mass had enlarged to greater
      than 30% of the thoracic diameter. The probability that this pattern of
      contiguous lymph node spread occurred by chance alone was very small. Hodgkin's
      disease spreads from the anterior mediastinal/paratracheal area in a contiguous
      manner. Exceptions are unusual enough that when they occur, diagnoses other than
      Hodgkin's disease are more likely.

PMID- 1999714
TI  - Multiple myeloma: VMCP/VBAP alternating combination chemotherapy is not superior
      to melphalan and prednisone even in high-risk patients.
AB  - The efficacy of alternating vincristine, melphalan (M), cyclophosphamide,
      prednisone/vincristine, carmustine, doxorubicin, and prednisone (VMCP/VBAP)
      polychemotherapy was compared with the M and prednisone (MP) regimen as induction
      treatment in multiple myeloma (MM). Three hundred four MM patients entered this
      study between March 1983 and July 1986; the analysis was performed in December
      1989. The treatment groups did not show significant differences with respect to
      major prognostic factors. Median overall survival was 33.8 months. In the
      VMCP/VBAP and MP arms, after 12 induction chemotherapy cycles, 59.0% and 47.3% (P
      less than .068) of the patients achieved an M component reduction greater than
      50%. No significant difference was observed in the two treatment arms in terms of
      remission duration (21.3 v 19.6 months, P less than .66) and survival (31.6 v
      37.0 months, P less than .28). Patients younger than 65 years did not show any
      advantage from the alternating polychemotherapy. At diagnosis, the plasma cell
      labeling index (LI) and serum beta-2 microglobulin (beta 2-m) were evaluated in
      173 and 183 patients, respectively. A significantly reduced survival was observed
      for patients with LI greater than or equal to 2% (16.4 months) or beta 2-m
      greater than or equal to 6 mg/L (20.4 months). Even in these poor-risk subgroups,
      VMCP/VBAP was not superior to MP.

PMID- 1999715
TI  - Inhibition of fluorouracil-induced stomatitis by oral cryotherapy.
AB  - Mucositis is a significant dose-limiting toxicity associated with fluorouracil
      (5FU), particularly when it is combined with leucovorin. We hypothesized that
      oral cryotherapy would cause local vasoconstriction and would temporarily
      decrease blood flow to the oral mucous membranes. If cryotherapy were used during
      the time of peak serum 5FU levels, then the oral mucous membranes would have less
      exposure to 5FU and thus develop less mucositis. To test this hypothesis, 95
      patients scheduled to receive their first cycle of 5FU plus leucovorin were
      randomized to have oral cryotherapy at the time of chemotherapy administration or
      to serve as a control group. Subsequent mucositis was significantly reduced in
      the group assigned to receive cryotherapy as judged by the attending physicians
      (P = .0002) and by the patients themselves (P = .0001). We now routinely
      recommend this cryotherapy procedure for our patients receiving daily bolus 5FU
      plus leucovorin.

PMID- 1999716
TI  - Concurrent cisplatin, infusional fluorouracil, and conventionally fractionated
      radiation therapy in head and neck cancer: dose-limiting mucosal toxicity.
AB  - After a preliminary dose-finding study involving 12 patients with advanced or
      locally recurrent head and neck cancer, 27 patients were treated on a phase II
      protocol, using fluorouracil 350 mg/m2/d by continuous intravenous (IV) infusion
      over 5 days, followed on the sixth day by a 2-hour IV infusion of cisplatin 50
      mg/m2, administered during the first and fourth weeks of radiation therapy to
      total doses between 60 and 64 Gy, using 2 Gy daily fractions. Eight of these 27
      patients had American Joint Committee on Cancer Staging (AJCC) stage III disease,
      and 12 had stage IV disease. Four had recurrent disease after surgery. Three-year
      follow-up is now available. Twenty-one (77.8%) remitted completely following
      treatment, and 11 remain free of local and regional relapse at 3 years. Four have
      developed systemic metastases. Following successful salvage treatment in two
      cases, estimated determinate survival at 3 years is 64%. Acute toxicity was
      manageable with this regime. Eleven instances of grade 3 Radiation Therapy
      Oncology Group/European Organization for Research and Treatment of Cancer
      (RTOG/EORTC) mucositis were observed, which caused interruptions to radiotherapy
      in only four cases. No late sequelae have so far been recorded. It is concluded
      that the protocol described is tolerable but probably did not cause a greater
      number of locoregional "cures" than would have been expected following
      conventional radiotherapy alone in this group of patients. The use of infusional
      fluorouracil with concurrent conventionally fractionated radiation therapy and
      cisplatin infusion results in mucositis that limits the dose of fluorouracil to
      levels that are probably subtherapeutic.

PMID- 1999717
TI  - Phase II trial of piritrexim in metastatic melanoma using intermittent, low-dose
      administration.
AB  - A phase II trial of piritrexim (2,4-diamino-6[2,5-dimethoxybenzyl]-5-methyl
      pyrido-[2,3d] pyrimidine, 301U74; PTX) was conducted for patients with metastatic
      malignant melanoma using an intermittent, low-dose oral administration schedule.
      PTX was administered at a starting dose of 25 mg orally three times per day for 5
      days weekly for 3 weeks followed by 1 week of rest. Thirty-one patients were
      entered onto the study. Among 31 patients assessable for response, there were two
      complete responses (CRs) and five partial responses (PRs) for a response rate (CR
      plus PR) of 23% (95% confidence limit, 10% to 42%). Five responses occurred in
      soft tissue lesions, and two responses occurred in lung lesions. The initial dose
      schedule was well tolerated. The dose-limiting toxicity was myelosuppression. PTX
      administered in this schedule appears to be active against malignant melanoma.
      Further clinical trials to confirm these results are underway.

PMID- 1999718
TI  - Occurrence of hypercalcemia and leukocytosis with cachexia in a human squamous
      cell carcinoma of the maxilla in athymic nude mice: a novel experimental model of
      three concomitant paraneoplastic syndromes.
AB  - Hypercalcemia and leukocytosis may occur in conjunction as paraneoplastic
      syndromes associated with malignant disease. Here we describe a human squamous
      cell carcinoma of the maxilla that was associated with hypercalcemia and
      leukocytosis, and also cachexia. The primary tumor was surgically removed and
      established in permanent cell culture. When either primary tumors or cultured
      tumor cells were inoculated into nude mice, the nude mice developed the same
      paraneoplastic syndromes as those which occurred in the patient from whom the
      tumor was originally derived. The plasma calcium was increased two and one-half
      fold and the WBC count 30-fold, and the body weight was decreased by 45% in tumor
      bearing animals. Each of these paraneoplastic syndromes was alleviated by
      surgical excision of the tumor, indicating that the paraneoplastic syndromes were
      due to a factor or factors produced by the primary tumor. The development of each
      of these paraneoplastic syndromes in nude mice correlated positively with the
      other two syndromes. We examined the organs of tumor-bearing mice and found
      striking histopathologic abnormalities in the bones, spleen, and liver, but no
      infiltration with tumor cells. The bones showed marked evidence of osteoclastic
      bone resorption. This model of a human tumor associated with the hypercalcemia
      leukocytosis paraneoplastic syndrome, together with cachexia, should make it
      possible to determine the mechanisms responsible for these paraneoplastic
      syndromes and their relationship to each other.

PMID- 1999719
TI  - A phase I trial of monoclonal antibody M195 in acute myelogenous leukemia:
      specific bone marrow targeting and internalization of radionuclide.
AB  - Ten patients with myeloid leukemias were treated in a phase I trial with
      escalating doses of mouse monoclonal antibody (mAb) M195, reactive with CD33, a
      glycoprotein found on myeloid leukemia blasts and early hematopoietic progenitor
      cells but not on normal stem cells. M195 was trace-labeled with iodine-131 (131I)
      to allow detailed pharmacokinetic and dosimetric studies by serial sampling of
      blood and bone marrow and whole-body gamma-camera imaging. Total doses up to 76
      mg were administered safely without immediate adverse effects. Absorption of M195
      onto targets in vivo was demonstrated by biopsy, pharmacology, flow cytometry,
      and imaging; saturation of available sites occurred at doses greater than or
      equal to 5 mg/m2. The entire bone marrow was specifically and clearly imaged
      beginning within hours after injection; optimal imaging occurred at the lowest
      dose. Bone marrow biopsies demonstrated significant dose-related uptake of M195
      as early as 1 hour after infusion in all patients, with the majority of the dose
      found in the marrow. Tumor regressions were not observed. An estimated 0.33 to
      1.0 rad/mCi 131I was delivered to the whole body, 1.1 to 6.1 rad/mCi was
      delivered to the plasma, and up to 34 rad/mCi was delivered to the red marrow
      compartment. 131I-M195 was rapidly modulated, with a majority of the bound
      immunoglobulin G (IgG) being internalized into target cells in vivo. These data
      indicate that whole bone marrow ablative doses of 131I-M195 can be expected. The
      rapid, specific, and quantitative delivery to the bone marrow and the efficient
      internalization of M195 into target cells in vivo also suggest that the delivery
      of other isotopes such as auger or alpha emitters, toxins, or other biologically
      important molecules into either leukemia cells or normal hematopoietic progenitor
      cells may be feasible.

PMID- 1999720
TI  - A phase I clinical, plasma, and cellular pharmacology study of gemcitabine.
AB  - A novel deoxycytidine analog, gemcitabine (2',2'-difluorodeoxycytidine [dFdC]),
      has been studied in a phase I clinical and pharmacology trial. Doses ranging from
      10 to 1,000 mg/m2 were administered over 30 minutes weekly times 3 weeks every 4
      weeks. The maximum-tolerated dose (MTD) was 790 mg/m2. The dose-limiting toxicity
      was myelosuppression, with thrombocytopenia and anemia quantitatively more
      important than granulocytopenia. Nonhematologic toxicity was minimal. Two
      responses in patients with adenocarcinomas of the colon and lung were documented.
      The maximum dFdC plasma concentration, reached after 15 minutes of infusion, was
      proportional to the total dose administered. Elimination, due mainly to
      deamination, was rapid (terminal half-life [t1/2], 8.0 minutes) and dose
      independent. The deamination product 2',2'-difluorodeoxyuridine (dFdU) was
      eliminated with biphasic kinetics characterized by a long terminal phase (t1/2,
      14 hours); it was the sole metabolite detected in urine. The concentration of
      dFdC 5'-triphosphate in circulating mononuclear cells increased in proportion to
      the dFdC dose at infusions between 35 and 250 mg/m2. No further increment in dFdC
      5'-triphosphate (dFdCTP) was observed at higher doses, which resulted in plasma
      dFdC concentrations greater than 20 mumol/L (350 to 1,000 mg/m2), suggesting
      saturation of dFdC 5'-phosphate accumulation. The recommended dose for phase II
      clinical trials in solid tumors is 790 mg/m2/wk.

PMID- 1999721
TI  - Quality-adjusted survival analysis.

PMID- 1999722
TI  - Chemotherapy, tamoxifen, and breast cancer: reconciling differences.

PMID- 1999723
TI  - Treatment of childhood Hodgkin's disease.

PMID- 1999724
TI  - Cyclophosphamide and the heart.

PMID- 1999725
TI  - Neurons that form multiple pattern generators: identification and multiple
      activity patterns of gastric/pyloric neurons in the crab stomatogastric system.
AB  - 1. The stomatogastric ganglion (STG) of decapod crustaceans has been
      characterized by its production of two motor patterns, the gastric mill rhythm
      and the pyloric rhythm. The period of the gastric rhythm is typically 5-10 s,
      whereas the period of the pyloric rhythm is approximately 1 s. 2. In the STG of
      the crab, Cancer borealis, we find routinely that many motor neurons are active
      in time with both the pyloric and gastric rhythms. We rigorously identified the
      motor neurons according to the muscles they innervate. Some neurons usually
      classified as members of the pyloric network can be active in time with the
      gastric rhythm. All of the gastric motor neurons except the dorsal gastric (DG)
      neuron can generate pyloric-timed firing patterns. 3. Two motor neurons innervate
      muscles found in several different regions of the stomach. The inferior cardiac
      (IC) neuron, usually considered part of the pyloric network, innervates cardiac
      sac, gastric mill, and pyloric muscles. The lateral posterior gastric (LPG)
      neurons innervate muscles of both the gastric mill and the pyloric chamber. 4.
      These data show that the gastric and pyloric networks in the crab are not
      separate groups of neurons that independently generate two different rhythmic
      behaviors. Rather, these neurons together provide a synaptically connected pool
      of neurons from which many different pattern-generating circuits can be
      assembled, under different physiological conditions.

PMID- 1999726
TI  - The olivocochlear efferent bundle and susceptibility of the inner ear to acoustic
      injury.
AB  - 1. The role of the efferent olivocochlear bundle (OCB) in protecting the inner
      ear from acoustic injury was studied in the anesthetized cat. Middle-ear muscles
      (MEM) were cut to eliminate possible effects of this feedback system on the
      auditory periphery. In each of a series of animals, the OCB was unilaterally
      transected. The animal was then exposed binaurally to an intense pure tone, and
      the resultant damage to the two sides compared by measuring threshold shifts in
      the compound action potential from each ear. Data from each animal provide one
      control measurement (threshold shift with an intact OCB) and one experimental
      measurement (threshold shift without a functional OCB). 2. Two experimental
      series were analyzed. In one the OCB was electrically stimulated, providing
      maximal firing rates in the efferents projecting to the control ear. In another
      series the OCB was not electrically stimulated: thus any OCB activity to the
      control ear was only that evoked by the acoustic stimulation itself. 3. In
      neither experimental series was there evidence that activity in the OCB provides
      protection from acoustic injury. These results are in disagreement with
      conclusions drawn from experiments with acoustic overstimulation of guinea pigs.
      4. Interpretations for the discrepancy between the present study and those on
      guinea pigs include interspecies differences and the possible contribution of the
      MEM reflex or cochlear blood-flow changes to previously observed effects.

PMID- 1999728
TI  - Picrotoxin- and 4-aminopyridine-induced activity in hilar neurons in the guinea
      pig hippocampal slice.
AB  - 1. Paired extra- and intracellular recording was used to study the activity of
      neurons in the dentate hilus and their interaction with CA3/CA4 pyramidal neurons
      and granule cells during picrotoxin- or 4-aminopyridine (4-AP)-induced rhythmical
      activity in the guinea pig hippocampal slice. 2. Picrotoxin induced synchronous
      repetitive population spikes in the CA3, CA4, and hilar region, but no
      extracellular activity in the granule cell layer. 4-AP induced rhythmically
      occurring positive field-potential waves in the CA3, CA4, and granular layer
      coincident to negative/positive field potentials in the hilus. 3. Picrotoxin
      induced activity originated in the CA3 area and subsequently appeared in the CA4
      and hilar region, whereas 4-AP-induced activity appeared simultaneously in all
      subfields. 4. Blockade of fast glutamatergic excitation by 6-cyano-7
      nitroquinoxaline-2,3-dione (CNQX, 10 microM) blocked the picrotoxin-induced
      activity but not the 4-AP-induced activity. 5. Focal application of tetrodotoxin
      (TTX) between area CA3 and CA4 blocked picrotoxin-induced activity in the CA4 and
      hilar region but decoupled 4-AP-induced activity in the CA3 area. 6. Under
      intracellular recording, picrotoxin induced bursts in CA3, CA4, and hilar neurons
      but K-dependent slow IPSPs in granule cells. 4-AP induced rhythmically occurring
      burst in hilar neurons synchronous to Cl- and K-dependent IPSPs in CA3, CA4, and
      granule cells. 7. Comparison of picrotoxin- and 4-AP-induced rhythmical burst
      activity reveals that many hilar neurons are excited by CA3/CA4 pyramidal neurons
      in addition to the well-known excitation by granule cells and perforant path
      fibers, and that, in turn, many hilar neurons inhibit CA3, CA4, and granule
      cells.

PMID- 1999727
TI  - Spatial distribution of nociceptive processing in the rat spinal cord.
AB  - 1. Quantitative 2-deoxyglucose (2-DG) experiments were undertaken to determine
      the spatial distribution of nociceptive responses in the rat spinal cord. Twenty
      unanesthetized, paralyzed rats with T2 transected spinal cords were divided into
      groups (n = 4) and stimulated with non-noxious (35 degrees C) or graded noxious
      temperatures (45 degrees, 47 degrees, 48 degrees, and 49 degrees C). Stimulation
      was delivered by cyclical immersion of one hind paw in a temperature-controlled
      water bath. 2. When stimulation began, 50 microCi of 2-DG was injected into the
      rat, and timed sequential blood samples were drawn to monitor plasma glucose and
      2-DG levels. On termination of stimulation, spinal cords were removed, sectioned,
      and prepared for autoradiography. Local rates of spinal cord metabolism were
      obtained by microcomputer analysis of autoradiographs. 3. Nociceptive stimulation
      produced increases in glucose utilization in some of the grey matter laminae
      previously implicated in nociceptive processing. Within the nociceptive range, 49
      degrees and 48 degrees C intensities elicited significantly greater responses
      than did 45 degrees C stimulation. 4. The rostrocaudal spatial distribution of
      nociceptive responses was most extensive within laminae V-VI with stimulus-evoked
      metabolic activity extending 9 mm from L2-L5. Similarly, metabolic increases
      occurred over 7 mm within lamina VII. In contrast, metabolic activity within the
      upper dorsal horn (laminae I-IV) extended only 3 mm and was limited to L4.
      Metabolic patterns within laminae VIII-IX sharply differed from those within
      other laminae in that no increases occurred within L4, although regions of L3 and
      L5 were responsive to stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1999729
TI  - Na(+)-current expression in rat hippocampal astrocytes in vitro: alterations
      during development.
AB  - 1. With the use of whole-cell patch-clamp recording. Na(+)-current expression was
      studied in hippocampal astrocytes in vitro, individually identified by filling
      with Lucifer yellow (LY) and staining for glial fibrillary acidic protein (GFAP)
      and vimentin. 2. The proportion of astrocytes that express Na+ currents in rat
      hippocampal cultures changes during development in vitro and decreases from
      approximately 75% at day 1 to approximately 30% after 10 days in culture. 3. The
      sodium currents expressed in astrocytes can be differentiated into two types on
      the basis of kinetics. At early times in culture the time course of Na+ currents
      is fast in both onset and decay with an average decay time constant of 1.27 ms,
      whereas after 6 days Na+ currents become comparatively slow and decayed with an
      average time constant of 1.86 ms. 4. As with the time-course of Na+ currents, the
      two age groups of astrocytes (i.e., days 1-5 and day 6 and older) differ with
      respect to their steady-state inactivation characteristics. Early after plating
      and up to day 5, the midpoint of the steady-state inactivation curve is close to 
      60 mV, as also observed in hippocampal neurons of various ages; in contrast,
      after 6 days in culture the curve is shifted by approximately 25 mV toward more
      hyperpolarized potentials with a midpoint close to -85 mV. 5. In contrast to h
      infinity-curves, current-voltage (I-V) curves of Na(+)-current activation were
      identical in all astrocytes studied and did not change with time in culture. 6.
      In astrocytes expressing Na+ currents, current densities (average of 35 pA/pF on
      day 1) decreased throughout the first 5 days and were almost abolished around
      days 4 and 5 in culture. Beginning on day 6, however, current densities increased
      again and maintained a steady level (average of 14 pA/pF) for the duration of the
      time period in culture (20 days). This biphasic time course closely correlates
      with the time course of changes in Na(+)-current kinetics and steady-state
      inactivation. 7. These data suggest that Na+ currents in cultured hippocampal
      astrocytes show characteristic changes with increasing time in culture. During
      the first 4-5 days in culture, hippocampal astrocytes display Na+ currents with
      properties similar to those of hippocampal neurons. Our data further suggest that
      Na+ currents with distinctive, "glial-type" characteristics are only expressed in
      hippocampal astrocytes after 6 days in culture.

PMID- 1999730
TI  - Characteristics of midbrain control of spinal nociceptive neurons and
      nonsomatosensory parameters in the pentobarbital-anesthetized rat.
AB  - 1. GABAergic mechanisms in the midbrain periaqueductal gray (PAG) have been
      proposed to control the activity of descending antinociceptive systems and
      defensive behavior. Here, the effect of neuronal disinhibition by gamma
      aminobutyric acid (GABAA) receptor blockade at midbrain sites on spinal neuronal
      responses to noxious and innocuous skin stimulation was quantitatively
      characterized. It was compared with the effect of direct neuronal excitation by
      glutamate microinjections or electrical stimulation at identical sites. Changes
      in mean arterial blood pressure and other nonsomatosensory responses were also
      assessed. 2. Responses of 101 multireceptive lumbar spinal dorsal horn neurons to
      noxious radiant skin heating (50 degrees C, 10 s), innocuous skin brushing, and
      electrical stimulation of primary afferent A- and C-fibers were recorded in
      deeply pentobarbital-anesthetized rats. The mean blood pressure was continuously
      monitored in one carotid artery, and other nonsomatosensory parameters, such as
      frequency and depth of spontaneous respiration and contractions of abdominal and
      facial muscles, were classified according to their relative intensity into five
      groups. 3. A fine, multibarrel glass pipette was constructed for monopolar
      electrical stimulation and microinjection of the GABAA receptor antagonist
      bicuculline (40, 200, or 400 pmol), or glutamate (10-50 nmol), or Fast Green dye
      in 50 or 100 nl at identical sites in the midbrain. 4. Bicuculline
      microinjections into discrete regions of the PAG selectively abolished spinal
      neuronal responses to noxious skin stimulation but did not affect brush-evoked
      responses or responses to electrical A-fiber stimuli. This antinociception was
      often, albeit not necessarily, accompanied by tachypnoea and abdominal and facial
      muscle contractions and changes--mostly increases--in mean arterial blood
      pressure. Injections into other areas of the PAG and adjoining ventral tegmentum
      (VT) were less effective. The vast majority of injection sites in the lateral
      tegmentum (LT) were ineffective. 5. Glutamate microinjections at midbrain sites
      to detect areas of origin of descending antinociceptive neurons were
      characterized by a high incidence (greater than 50%) of false-negative results,
      as bicuculline was shown to be effective at numerous glutamate-insensitive sites.
      Glutamate microinjections into some sites of the PAG and adjoining VT reduced,
      but did not abolish, spinal neuronal responses to noxious skin heating.
      Injections into the LT were ineffective. 6. The efficacy of electrical
      stimulation at midbrain sites on spinal nociceptive responses had no predictive
      value for the effect of glutamate or bicuculline.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 1999731
TI  - Intracellular measurements from a rapidly adapting sensory neuron.
AB  - 1. The femoral tactile spine of the cockroach contains a single sensory neuron
      with its cell body in the lumen of the spine. Step movements of the spine produce
      rapidly adapting bursts of action potentials that decay to 0 in 1 s. Previous
      work has shown that a large part of this adaptation occurs during action
      potential encoding. 2. Intracellular recordings from the tactile spine neuron
      were obtained by lowering a microelectrode through the spine lumen and
      penetrating the cell body. Injection of Lucifer yellow followed by fluorescence
      microscopy confirmed the morphology of the soma, with a diameter of 30 microns,
      and showed an axon of 9 microns leaving the spine and proceeding proximally along
      the femur. 3. Membrane-potential records were digitized and examined at high
      resolution during bursts of action potentials produced by depolarizing current
      pulses. No significant changes in action potential shape were detected during
      adaptation. However, the rate of depolarization between action potentials slowed
      dramatically during the burst. This slowing could be reduced and the burst
      substantially prolonged by chloramine-T (CT), an agent that reduces sodium
      channel inactivation in several preparations. 4. A 100 Hz sinusoidal current was
      superimposed on depolarizing current pulses to test for changes in membrane
      conductance during a burst of action potentials. No such changes were detected,
      indicating that rapid adaptation is not due to changes in membrane
      permeability.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1999732
TI  - Excitatory postsynaptic potentials evoked by ventral root stimulation in neonate
      rat motoneurons in vitro.
AB  - 1. Intracellular recordings were made from antidromically identified motoneurons
      in transverse (500 microns) lumbar spinal cord slices of neonatal (12-20 day)
      rats. 2. Electrical stimulation of ventral rootlets evoked, with or without an
      antidromic spike or initial segment potential, a depolarizing response (latency,
      1-4.2 ms), a hyperpolarizing response (latency, 1.5-3.5 ms), or a combination of
      two preceding responses in 38, 6, and 8% of motoneurons investigated. 3. The
      hyperpolarizing response was reversibly eliminated by low Ca2+ (0.25 mM), d
      tubocurarine (d-Tc; 10 microM) or strychnine (1 microM), suggesting that this
      response represents an inhibitory post-synaptic potential (IPSP) mediated by
      glycine or a related substance release from inhibitory interneurons subsequent to
      their activation by axon collaterals in a manner analogous to the Renshaw cell
      circuitry described for the cat motoneurons. 4. The depolarizing responses were
      excitatory postsynaptic potentials (EPSPs), because they could be graded by
      varying the stimulus intensity and were reversibly abolished in low Ca2+
      solution. 5. Membrane hyperpolarization increased the amplitude of EPSPs, and the
      mean extrapolated reversal potential was -4 mV. 6. EPSPs were augmented, rather
      than diminished, by dihydro-beta-erythroidine (1 microM) or d-Tc, arguing against
      a role of recurrent motor axon collaterals in initiating the responses. 7. The
      conduction velocity of the fibers initiating the EPSPs ranged from 0.35 to 0.96
      m/s, indicating that these fibers were unmyelinated. Furthermore, the EPSP
      exhibited a constant delay when the stimulus frequency was varied from 1 to 5 Hz,
      and the synaptic delay estimated by extrapolation was less than 1 ms, suggesting
      that it was a monosynaptic event. 8. After complete separation of the ventral and
      dorsal horns by a knife cut, stimulation of ventral rootlets could still evoke an
      EPSP in motoneurons. 9. Superfusion of the slices with the nonselective glutamate
      receptor antagonist kynurenic acid (0.2-1 mM) or the selective
      quisqualate/kainate receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX)
      (0.5-1 microM) reversibly diminished the EPSPs. 10. EPSPs evoked by stimulation
      of dorsal and ventral rootlets exhibited different latency and waveform in the
      same motoneurons. 11. The results provide evidence that activation of ventral
      root afferents evoked an EPSP mediated by glutamate or a related substance in a
      population of motoneurons. Furthermore, the afferent pathway mediating the EPSP
      appears to be monosynaptic and confined to the ventral horn.

PMID- 1999733
TI  - The influence of noise on quantal EPSP size obtained by deconvolution in spinal
      motoneurons in the cat.
AB  - 1. The amplitudes of quantal components that make up single-fiber excitatory
      postsynaptic potentials (EPSPS) were determined by a deconvolution technique and
      by simulation studies and were compared with the background noise. 2. A strong
      correlation was found between the sizes of EPSP quantal components and the
      standard deviation of the noise from which the data were extracted by
      deconvolution. A similar correlation was then shown in published data from
      several other laboratories. 3. EPSPS having amplitudes less than 100 microV were
      recorded that had little or no variance in their amplitudes. Most of these EPSPS
      showed a much smaller peak variance than would be expected if they fluctuated
      among amplitudes in steps of approximately 100 microV--the proposed mean value
      for the amplitude of the quantal EPSP. 4. Deconvolution of simulated data with
      the maximum likelihood algorithm resulted in the suppression of components less
      than 1.5 SD of the background noise. The remaining components were approximately
      equally spaced. No way was found to detect this error, and rejection of
      deconvolved data with components less than 1.5 noise SD did not eliminate it. The
      resulting erroneous data showed a strong correlation between the amplitudes of
      the components obtained and the noise standard deviation. 5. It is concluded that
      at least some EPSPS generated by single Ia-afferents on motoneurons are composed
      of quantal components significantly less than 100 microV and that deconvolution
      procedures are not capable of detecting such small components.

PMID- 1999734
TI  - Gustatory neural coding in the monkey cortex: stimulus intensity.
AB  - 1. We analyzed the activity of single neurons in gustatory cortex of alert
      cynomolgus monkeys in response to a range of stimulus intensities. Chemicals were
      deionized water, fruit juice, and several concentrations of the four prototypical
      taste stimuli: 10(-3)-1.0 M glucose, 10(-3)-1.0 M NaCl, 10(-4)-3 x 10(-2) M HCl,
      and 10(-5)-3 x 10(-3) M quinine HCl. 2. Taste-evoked responses could be recorded
      from a cortical gustatory area that measured 2.5 mm in its anteroposterior
      extent, 6.0 mm dorsoventrally, and 3.0 mm mediolaterally. Taste-responsive cells
      constituted 62 (3.7%) of the 1,661 neurons tested. Nongustatory cells gave
      responses associated with mouth movement (10.1%), somatosensory stimulation
      (2.2%), and approach or anticipation (0.9%). 3. Intensity-response functions were
      determined across 62 gustatory neurons. Neural thresholds for each stimulus
      quality conformed well to human psychophysical thresholds. Mean discharge rate
      was a direct function of stimulus concentration for glucose, NaCl, and quinine
      HCl. The most effective of the basic stimuli was glucose. 4. Power function
      exponents were calculated from the responses of neural subgroups most responsive
      to each basic stimulus. Those for glucose, NaCl, and quinine were within the
      range of psychophysically derived values. Thus the perceived intensity of each
      basic quality is presumably based on the activity of the appropriate neural
      subgroup rather than on the mean activity of all taste cells. 5. The mean breadth
      of-tuning (entropy) coefficient for 62 gustatory neurons was 0.65 (range, 0.00
      0.98). 6. There was no clear evidence of chemotopic organization in the gustatory
      cortex. 7. An analysis of taste quality indicated that sweet stimuli evoked
      patterns of activity that were clearly distinct from those of the nonsweet
      chemicals. Among the latter group, NaCl was differentiable from HCl and quinine
      HCl, whose patterns were closely related. 8. The response characteristics of
      cortical taste cells imply gustatory thresholds and intensity-response functions
      for the nonhuman primate that conform well to those reported in psychophysical
      studies of humans, reinforcing the value of this neural model for human taste
      intensity perception.

PMID- 1999735
TI  - Transcultural concepts applied to nursing administration.

PMID- 1999736
TI  - Administrative fellowship. A bridge to success.
AB  - The transition from graduate administration student to nurse manager is
      difficult. One method of easing the transition is an administrative fellowship
      program. An administrative fellowship serves as a bridge between graduate
      education and management practice by providing the fellow with a supportive
      environment in which to operationalize theoretical knowledge. For the nursing
      department, it can be an effective way to recruit and select talented nurse
      managers for a challenging position.

PMID- 1999737
TI  - Nursing administration model for administrative practice.
AB  - The winds of change have swept in a new era for nursing. Complex decisions can be
      aided by a conceptual model for nursing administration practice. The authors
      discuss how the Iowa Model of Nursing Administration can be used by nurse
      administrators to solve administrative problems. Two practical examples are
      described.

PMID- 1999738
TI  - Predicting the marginal cost of direct nursing care for newborns.
AB  - The author describes a study on the cost of nursing care for newborns using cost
      functions. A sample of 70 institutions in New Jersey were studied during a 2-year
      period. The models explained 95% of the variation of nursing costs in the study
      population. This information can be used by nurse executives to more
      appropriately make decisions about optimal unit size and the profitability of
      certain services.

PMID- 1999739
TI  - The nursing shortage: crisis as opportunity.

PMID- 1999740
TI  - Accessing the source of leadership: a new paradigm for leadership development.

PMID- 1999741
TI  - Reflections on organizational structure and redesign.

PMID- 1999743
TI  - Program directors' attitudes towards residents' care of patients who have AIDS.
AB  - OBJECTIVE: To evaluate the educational strategies and experiences of residency
      programs regarding the training of primary care providers in the care of patients
      who have AIDS. DESIGN: Cross-sectional, self-administered questionnaire survey.
      SETTING: Survey conducted November 1988-April 1989. PARTICIPANTS: All 771 non
      military U.S. internal medicine and family medicine program directors were
      surveyed; 80% responded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:
      While 91% of the directors felt that primary care of AIDS patients was an
      important educational experience and 94% reported that their programs usually had
      AIDS inpatients, only 16% reported that the majority of trainees cared for AIDS
      patients in their continuity clinics. Even at programs that typically had six or
      more AIDS inpatients, only 26% of directors reported that most residents had
      cared for an AIDS patient in their continuity clinics. Among the 57% who did not
      believe or were unsure whether their residents were adequately trained in AIDS
      ambulatory care, only 38% reported improving resident education in this area to
      be a high priority. Among the 39% who did not encourage residents' assumption of
      primary care, 60% had at least one of the following concerns: AIDS care too
      stressful for residents (24%), AIDS care too complicated for generalists (31%),
      or clinic faculty not qualified to supervise residents' caring for AIDS patients
      (39%). CONCLUSION: Although program directors view education in AIDS ambulatory
      care as important, most do not believe that residents are adequately trained,
      many do not encourage residents' assumption of primary care of AIDS patients, and
      residents usually have not provided such care in their programs. Strategies to
      augment residents' ambulatory experience in AIDS care are needed.

PMID- 1999742
TI  - Increasing the efficacy of physician-delivered smoking interventions: a
      randomized clinical trial.
AB  - OBJECTIVE: To assess the relative impacts of three physician-delivered smoking
      interventions in combination with follow-up contact from behavioral counselors.
      DESIGN: Randomized controlled trial with pre- post measures of smoking rates.
      This paper reports six-month outcome data. SETTING: Participants were recruited
      from among patients seen by 196 medical and family practice residents in five
      primary care clinics. PARTICIPANTS: Participants were 1,286 patients out of 1,946
      eligible smokers approached. The patient group was 57% female and 91% white, had
      an average age of 35 years, and smoked, on average, slightly over one pack per
      day. INTERVENTION: Physicians were trained to provide each of three
      interventions: advice only, brief patient-centered counseling, and counseling
      plus prescription of nicotine-containing gum (Nicorette). Half the patients
      received follow-up in the form of telephone counseling at three-monthly intervals
      from behavioral counselors. MEASUREMENTS AND MAIN RESULTS: Changes in smoking
      behaviors were assessed by telephone interview six months after physician
      intervention. The differences in one-week point prevalence cessation rates among
      the physician interventions were significant (p less than 0.01): advice only,
      9.1%; counseling, 11.9%; counseling plus gum, 17.4%; with no effect for telephone
      counseling. The time elapsed from physician encounter to initial quitting and the
      length of that period of abstinence also showed significant benefit of the
      counseling interventions. Patients receiving physician counseling were much more
      likely than those not receiving counseling to rate their physician as very
      helpful (p less than 0.001). Multiple regression analyses are also reported.
      CONCLUSION: Smoking intervention counseling provided by physicians is well
      received by patients and significantly increases the likelihood of cessation at
      six months, an effect that is augmented by the prescription of nicotine
      containing gum, when compared with physician-delivered advice. Follow-up
      telephone counseling does not contribute significantly to smoking behavior
      changes.

PMID- 1999744
TI  - Differences in access to zidovudine (AZT) among symptomatic HIV-infected persons.
AB  - OBJECT: To evaluate socioeconomic factors that determine whether symptomatic HIV
      infected persons are offered zidovudine (AZT). DESIGN: Cross-sectional survey
      conducted as part of the Robert Wood Johnson Foundation's AIDS Health Services
      Program. SETTING: Public hospital clinics and community-based AIDS organizations
      in nine American cities. PATIENTS: 880 HIV-seropositive outpatients interviewed
      between October 1988 and May 1989. MAIN RESULTS: Males were more likely to have
      been offered AZT than were females (adjusted odds ratio 2.99; 95% confidence
      interval 1.67 to 5.36), those with insurance were more likely to have been
      offered AZT than were those without (adjusted odds ratio 2.00; 95% confidence
      interval 1.25 to 3.21), and whites more likely to have been offered AZT than were
      non-whites (adjusted odds ratio 1.73; 95% confidence interval 1.11 to 2.69).
      Intravenous drug users were less likely to have been offered AZT than were non
      drug users (adjusted odds ratio 0.44; 95% confidence interval 0.28 to 0.69).
      Persons who had had an episode of Pneumocystis carinii pneumonia were more likely
      to have been offered AZT than were persons who had AIDS and had not had
      Pneumocystis carinii pneumonia (adjusted odds ratio 2.95; 95% confidence interval
      1.71 to 5.11). CONCLUSION: The authors conclude that traditionally disadvantaged
      groups have less access to AZT, the only antiretroviral agent demonstrated to
      increase survival of patients who have symptomatic HIV infection.

PMID- 1999745
TI  - Will outpatients complete living wills? A comparison of two interventions.
AB  - OBJECTIVE: To test the efficacy of two intervention methods that aimed to
      increase the percentage of adult clinic patients who completed living wills and
      placed them on file with their physicians within a four-month period. DESIGN:
      There were one control and two intervention groups. Surveys were separated by age
      and gender categories and randomly selected for the final sample. SETTING: The
      internal medicine outpatient clinic of a large tertiary hospital. PARTICIPANTS:
      All patients who visited the clinic were asked whether they would be willing to
      fill out a survey. The final sample included 167 adult patients who comprised
      three study groups. INTERVENTIONS: The first intervention relied solely on a
      booklet that described the Minnesota Living Will Act, general information
      concerning advance directives, and medical interventions that could be considered
      extraordinary if used for a patient in a terminal condition. The second
      intervention relied on both the booklet and repeated physician-initiated
      discussions with the patient about the probable value of a living will. MAIN
      RESULTS: The booklet/physician intervention was found to be significantly more
      effective than either the booklet-only intervention or no intervention (p less
      than 0.05 and 0.01, respectively). CONCLUSIONS: The physician intervention used
      in this population could be undertaken in any primary care clinic. Time spent in
      discussion before a crisis may be significantly shorter and qualitatively better
      than time spent in discussion with families who must make decisions during a
      crisis.

PMID- 1999746
TI  - Healthy patients who perceive poor health and their use of primary care services.
AB  - OBJECTIVE: To determine what proportion of patients who have poor health
      perceptions are physically healthy and to explore why some patients perceive a
      healthy state while others perceive illness. DESIGN: A prospective consecutive
      series of office patients completed the Rand Corporation's General Health
      Perceptions Questionnaire, and their physicians rated their physical health.
      Their use of health care services was determined for the following 12 months.
      SETTING: A rural teaching office practice. PATIENTS: Of 243 adult patients asked
      to complete the questionnaire, 32 were excluded, for dementia (8), illiteracy
      (4), illness (8), incomplete questionnaires (6), and other reasons (6). 208
      patients (86%) formed the final study group. MEASUREMENTS AND MAIN RESULTS: 62 of
      208 patients had poor health perception scores. 39 of the 62 were rated by
      physicians as physically healthy and were not statistically different in physical
      health ratings or numbers of prescribed medications from the 146 patients who had
      higher health perception scores. However, these 39 patients had significantly
      more health-related worry, acute pain, and depression than did the other 146
      patients. They also made more office visits and telephone calls and had higher
      total primary care charges. CONCLUSIONS: This study suggests that 21% of adult
      primary care patients (39 of 208) have health perceptions lower than expected for
      their levels of physical health. These low health perceptions are correlated with
      increased emotional distress and higher utilization of health care resources.
      Strategies to identify these patients and interventions to improve their views of
      their health could reduce utilization.

PMID- 1999747
TI  - Primary care-based dermatology practice: internists need more training.
AB  - OBJECTIVE: To evaluate the ability of teachers in an internal medicine clinic to
      appropriately diagnose, treat, and refer for specific dermatologic disorders.
      DESIGN: Prospective study. SETTING: Medical school-affiliated primary care
      clinic. PATIENTS/PARTICIPANTS: Case presentations of 20 patients who had
      dermatologic problems were prepared in the form of photographs with accompanying
      histories. All cases were presented to 17 of 21 available faculty internists who
      answered questions concerning diagnosis and management of the cases on a
      questionnaire. The responses of three board-certified faculty dermatologists were
      used as a reference standard. MEASUREMENTS AND MAIN RESULTS: The internists had
      had an average of three weeks' total formal dermatology training. Overall, 60% of
      cases were correctly diagnosed by the internists and 89% of these were either
      treated appropriately or referred to dermatologists. In 40% of incorrectly
      diagnosed cases, internists failed to refer and the majority of these were
      treated inappropriately. Of referrals deemed appropriate by dermatologists, only
      62% were made. Conversely, 33% of referrals were deemed unnecessary. CONCLUSIONS:
      Faculty internists were able to diagnose many common skin diseases despite having
      received little dermatology training. However, errors in diagnosis occurred
      frequently and when diagnoses were incorrect there was a tendency to mismanage.
      These data suggest that the current amount of dermatology training is inadequate
      to prepare future primary care physicians for their increased role in the
      management of skin disorders.

PMID- 1999748
TI  - Inability to demonstrate physiologic correlates of subjective improvement among
      patients taught the relaxation response.
AB  - OBJECTIVE: To assess whether the regular elicitation of the relaxation response
      produces sustained physiologic changes coincident with symptomatic relief or
      improved psychological state. DESIGN: Prospective, cohort pilot study. SETTING:
      Clinical research center within a teaching hospital. PATIENTS: Thirteen athletic
      men, mean age 44.8 years, with borderline or labile hypertension, taking no
      medication. All 13 completed the study. INTERVENTIONS: Three baseline assessments
      of psychological state, symptom checklist, and assessment of autonomic response
      to infusion of beta agonist (isoproterenol). Daily relaxation response exercises
      for five consecutive weeks followed by repeat assessment of all parameters.
      Discontinuation of relaxation exercises for subsequent five weeks followed by
      repeat assessment of all parameters. MEASUREMENTS AND MAIN RESULTS: After
      eliciting the relaxation response, subjects demonstrated significant decreases in
      anxiety (p less than 0.014) and somatic symptoms (p less than 0.02).
      Psychological and somatic variables returned toward baseline after the subsequent
      discontinuation of relaxation exercises. No significant concomitant change in
      urinary catecholamines, heart rate response to isoproterenol, blood pressure,
      pulse rate, or serum cholesterol was demonstrated. CONCLUSION: The regular
      elicitation of the relaxation response can improve psychological performance and
      reduce symptoms. However, the physiologic mechanism whereby these psychological
      and symptomatic improvements occur remains poorly understood and warrants further
      investigation.

PMID- 1999749
TI  - What do you do when the blood pressure is up? An approach to the known
      hypertensive who has an elevated blood pressure.

PMID- 1999750
TI  - The etiology and clinical significance of pseudoascites.

PMID- 1999752
TI  - Can residents be trained to counsel patients about quitting smoking? Results from
      a randomized trial.
AB  - STUDY OBJECTIVE: To evaluate the effectiveness of two teaching interventions to
      increase residents' performance of smoking cessation counseling. DESIGN:
      Randomized controlled factorial trial. SETTING: Eleven residency programs, in
      internal medicine (six), family medicine (three), and pediatrics (two). Programs
      were located in three university medical centers and four university-affiliated
      community hospitals. PARTICIPANTS: 261 residents who saw ambulatory care patients
      at least one half-day per week, and 937 returning patients aged 17 to 75 years
      who reported having smoked five or more cigarettes in the preceding seven days.
      Of the 937, 843 were eligible for follow-up, and 659 (78%) were interviewed by
      phone at six months. INTERVENTIONS: Two interventions (tutorial and prompt) and
      four groups. The tutorial was a two-hour educational program in minimal-contact
      smoking cessation counseling for residents. The prompt was a chart-based reminder
      to assist physician counseling. One group of residents received the tutorial;
      one, the prompt; and one, both. A fourth group received no intervention.
      MEASUREMENT AND RESULTS: Six months after the intervention, physician self
      reports showed that residents in the tutorial + prompt and tutorial-only groups
      had used more counseling techniques (1.5-1.9) than had prompt-only or control
      residents (0.9). Residents in all three intervention groups advised more patients
      to quit smoking (76-79%) than did control group residents (69%). The tutorial had
      more effect on counseling practices than did the prompt. Physician confidence,
      perceived preparedness, and perceived success followed similar patterns. Exit
      interviews with 937 patients corroborated physician self-reports of counseling
      practices. Six months later, self-reported and biochemically verified patient
      quitting rates for residents in the three intervention groups (self-reported: 5.3
      8.2%; biochemically verified: 3.4-5.7%) were higher than those for residents in
      the control group (self-reported: 5.2%; biochemically verified: 1.7%), though the
      differences were not statistically significant. CONCLUSION: A simple and feasible
      educational intervention can increase residents' smoking cessation counseling.

PMID- 1999751
TI  - Pressure sores in the elderly: can this outcome be improved?

PMID- 1999754
TI  - More information needed.

PMID- 1999753
TI  - Incorporating smoking interventions into medical practice: taking the next step.

PMID- 1999755
TI  - Photocopying ECGs for all patients.

PMID- 1999756
TI  - Quantifying coffee consumption.

PMID- 1999757
TI  - Semi-automated fluorometric assay for urinary total and B N-acetyl-beta-D
      glucosaminidase: analytical investigation.
AB  - Total N-acetyl-beta-D-glucosaminidase (NAG) and NAG-B isoenzyme determination are
      determined in order to investigate renal tubular function. Here, we propose a
      semi-automated adaptation of Sandman's manual method for the Monarch centrifugal
      analyzer. Fluorescence of the released 4-methylumbelliferone is automatically
      read and results are directly expressed in nanokatal/l. Mean (1 SD) values
      expressed in nanokatal/millimole creatinine in urine from healthy female (n = 30)
      and male (n = 30) subjects were 8.2 (4.0) and 7.8 (2.9) for total NAG and 1.9
      (1.4) and 1.5 (0.7) for the NAG-B isoenzyme activity. The assay of six patients
      with various renal disorders shows definite increase in total NAG and NAG-B
      isoenzyme activities.

PMID- 1999758
TI  - New assay to detect shedding antigen with use of anti-idiotypic monoclonal
      antibodies.
AB  - Anti-idiotypic (Anti-Id) monoclonal antibodies (MoAbs) against anti
      carcinoembryonic antigen (CEA) monoclonal antibody 5B3 (IgG1) were prepared and
      characterized. Five anti-Id MoAbs recognized the private idiotype of MoAb 5B3.
      Idiotype mapping suggested that MoAb 5B3 had at least three distinct idiotopes at
      its antigen combining site. Utilizing the inhibition of idiotype-anti-idiotype
      interaction with use of anti-Id MoAb T4-305 or T4-212, an immunoassay to detect
      shedding CEA was established. The results of this inhibition assay correlated
      with those of double determinant immunoassay and inhibition percentages linearly
      increased in a CEA concentration-dependent manner. Since it requires only one
      epitope of a given antigen molecule, this assay could be widely used for
      detection of shedding antigens, including tumor-associated antigens.

PMID- 1999759
TI  - Human melanoma metastasis culture supernatant contains chemotactic factors for
      phagocytes.
AB  - Several findings point out that melanoma culture supernatants release soluble
      factors which modulate mononuclear cell chemotactic responsiveness. In this
      regard, either an enhancement or an impairment of chemotactic capacity has been
      found. Here, we provide evidence that supernatant recovered from human melanoma
      cell metastasis culture is able to trigger monocyte and polymorphonuclear cell
      chemotaxis. This activity is not affected by the presence of anti-IL-1 antibody
      during the assay. Further studies are in progress to isolate and characterize
      soluble factors involved in this activity.

PMID- 1999760
TI  - Evaluation of a bench-top nephelometric immunoassay analyzer.
AB  - We evaluated the Technicon DPA-1 immunoassay analyzer on its analytical
      characteristics. Therefore we studied three assays: albumin in cerebrospinal
      fluid and IgG and transferrin in serum. When tested with the Cusum test for
      linearity albumin, IgG, and transferrin measurements showed no deviation from
      linearity. Closer examination revealed an abrupt difference of recovery (from 99
      to 87%) in the albumin assay when the automatic dilution changed over from the
      primary analytical to the high analytical concentration range. One calibration
      was found sufficient for at least 14 days of measurement. Imprecision was well
      below the critical limits for reproducibility. We found reasonable agreement
      between the results from the DPA-1 and the results from comparison methods.
      However, the correlation plot of IgG showed lack of fit at a distinct segment of
      the regression line. This appeared to be caused by the poor recovery of the DPA-1
      at the lower limit of the high analytical concentration range. The assays of IgG
      and transferrin were found insensitive for interference by hemoglobin,
      triglycerides, urea, and bilirubin. The albumin assay was found sensitive for
      bilirubin and triglycerides. No reagent- and sample-to-sample carry-over could be
      detected in the assays evaluated.

PMID- 1999761
TI  - Time-resolved fluorometric sandwich immunoassay for human growth hormone in serum
      and urine.
AB  - A specific and sensitive time-resolved fluorometric sandwich immunoassay for
      human growth hormone (hGH) in serum and urine is described. A monoclonal anti-hGH
      IgG1 (5802)-coated polystyrene ball was incubated with serum or dialyzed urine
      and subsequently with europium ion-labeled monoclonal anti-hGH IgG1 (5801).
      Europium ion bound to the polystyrene ball was measured by time-resolved
      fluorometry. The detection limit of hGH was 0.3 pg/tube, which was 15-fold higher
      than that by sandwich enzyme immunoassay using horseradish peroxidase as label.
      The assay range of serum hGH was 15-15,000 ng/liter using 20 microliters of
      serum. The assay range of urinary hGH was 2-2,000 ng/liter using 150 microliters
      of dialyzed urine. The detection limits of hGH in serum and urine by this
      immunoassay were satisfactory for measuring hGH levels in serum and urine of
      healthy children and in serum of healthy adults and higher levels but not in
      urine of healthy adults and in serum and urine of patients with hGH deficiency.

PMID- 1999762
TI  - Quantitation of anti-tetanus and anti-diphtheria antibodies by enzymoimmunoassay:
      methodology and applications.
AB  - We have developed enzymoimmunoassays (EIA) for the quantitation of antibodies
      (Ab) to tetanus and diphtheria toxoids (TT, DT) using Immulon I plates coated
      with the appropriate toxoid. A preparation of human tetanus immunoglobulin with a
      known concentration of anti-TT Ab was used as calibrator of the anti-TT antibody
      assay. The assay of anti-DT Ab is calibrated with a pool of human sera whose anti
      DT Ab concentration was determined by quantitative immunoelectrophoresis, using a
      horse anti-DT with known Ab concentration as calibrator. A peroxidase-conjugated
      anti-human IgG was used in both assays. ABTS was used as substrate, and the
      reaction was stopped after 1 min incubation with citric acid and the OD measured
      at 414 nm on a Vmax reader. The assays have been applied to a variety of clinical
      situations. In patients suspected of having tetanus, the quantitation of
      antibodies has been helpful in establishing a diagnosis. In patients with a
      history of hypersensitivity to tetanus toxoid, verification of the levels of anti
      TT antibody may prevent unnecessary and potentially harmful immunizations. The
      assays have also been used for the diagnostic evaluation of the humoral immune
      response to TT and DT, both in pediatric patients and in immunosuppressed
      patients. Several non-responders have been detected, and we have recently used
      the assay to monitor the effects of fish oil administration on the humoral immune
      response.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1999763
TI  - Detection of anti-nuclear antibodies from patients with systemic rheumatic
      diseases by ELISA using HEp-2 cell nuclei.
AB  - A microtiter plate was coated with cell nuclei from HEp-2 cells, and the
      stabilized nuclei were fixed with acetone for an enzyme-linked immunosorbent
      assay (ELISA). Autoantibodies against nuclear antigens were detected from the
      sera of patients with various systemic rheumatic disease but not from healthy
      individuals by means of the nucleus ELISA procedure. Ninety-one percent of
      antinuclear antibody (ANA)-positive sera as demonstrated by immunofluorescence
      (IF) test were also judged as positive for ANAs by the nucleus ELISA and 5% of
      them as pseudo-positive. Patient's sera with homogeneous and fine-speckled IF
      patterns displayed the highest ELISA titers. A large portion of ss-A/Ro antigen
      is localized in the cytoplasm; therefore, anti-ss-A/Ro antibody was hardly
      detected by nucleus ELISA. The population of ANAs detectable by nucleus ELISA
      included anti-ss-B/La, anti-DNA, anti-histone, anti-Sm, anti-RNP, and anti-scl
      70.

PMID- 1999764
TI  - Infant feeding effects on flow cytometric analysis of blood.
AB  - Flow cytometric analysis was performed on purified mononuclear cells isolated
      from whole blood samples of 11 adults, 7 breast-fed (BF) infants and 11 formula
      fed (FF) infants, mean ages 34.2 +/- 4.3 years, 6.3 +/- 1.3 months, and 6.2 +/-
      1.2 months, respectively. Infants were receiving at least 70% of calories from
      formula or breast milk. Infant mononuclear cell populations contained a higher
      percentage of lymphocytes and a lower percentage of monocytes compared with
      adults. Within the lymphocyte population, infants had a higher CD4+/CD8+ ratio (T
      helper-inducer/T cytotoxic-suppressor), a higher percentage of CD19+ (pan B) and
      CD4+ cells, and a lower percentage of CD8+ and CD16+ (natural-killer) cells
      compared with adults. CD3+ (pan T) and CD4+ lymphocyte percentages were higher
      and CD19+ lymphocyte percentages were lower in FF compared with BF infants.
      Although sample size is small, our data indicate that diet may influence
      lymphocyte subset distribution during infancy when the majority of calories is
      derived from infant formula or human milk.

PMID- 1999765
TI  - State-of-the-art of zidovudine monitoring.
AB  - Zidovudine, the only drug approved by the FDA for the treatment of AIDS, has well
      documented efficacy, but numerous toxic side effects. Despite considerable
      knowledge of the pharmacology of the drug, however, a therapeutic concentration
      range has not been established. This article reviews methodologies used for
      measurement of zidovudine in serum. Procedures for several methods are described
      and comparisons offered. In addition to methodologies, other issues of concern in
      establishing or maintaining a zidovudine monitoring service are also discussed,
      including the clinical relevance of routine zidovudine monitoring, method-related
      quality control, and laboratory safety. Methodologies currently being developed
      to measure the active intracellular metabolites of zidovudine are also described.
      These methods are believed to be the key to fully understanding the relationships
      between zidovudine pharmacology, toxicity, and efficacy.

PMID- 1999766
TI  - Monitoring of cyclosporine concentrations by using dry blood-spot samples.
AB  - We modified the Incstar Cyclo Trac SP kit to enable its use with dry blood-spots
      on filter paper. The recovery ranged from 92 to 106%. Dilution studies have shown
      excellent linearity and parallelism throughout the range of the assay. Precision
      is demonstrated by within-assay CV's of 6.6 and 4.3% at 96 and 342 micrograms/L
      respectively and between-assay CV's of 9.1 and 7.0% at 138 and 506 micrograms/L
      respectively. A comparison study (n = 209) with whole blood assay gave a
      correlation coefficient of 0.97, a slope of 1.04, and an intercept of 13.2. Whole
      blood and dry blood-spot cyclosporine assays on heart, kidney, liver, and lung
      transplants were also compared.

PMID- 1999767
TI  - Hematopoietic growth factors: a new frontier in immunotherapy.

PMID- 1999768
TI  - Pathogenesis and recent therapeutic approaches to graft-versus-host disease.
AB  - Effective prophylaxis of acute GVHD should bring about improved patient survival
      by decreasing severe infections during the first 3 months after transplantation
      and reducing the incidence of chronic GVHD while not compromising the quality of
      hematopoietic engraftment or increasing the incidence of leukemic relapse by
      impairing the graft-versus-leukemia effect. None of the current approaches to
      prevention of GVHD succeed at meeting these expectations, although postgrafting
      immunosuppressive therapy comes closest to the ideal. The technique of T cell
      depletion has been very effective in reducing the incidence of GVHD, but
      conditioning programs must be developed that will be more successful at
      eliminating host immune and malignant cells. It is doubtful that this will be
      achieved with systemic chemotherapy and total body irradiation. Innovative
      approaches such as the use of monoclonal antibodies, either alone or linked to
      short-lived radioactive isotopes with short linear energy transfer, promise to
      result in less toxic but more efficient programs, not only providing better
      eradication of malignant disease but also ameliorating the problem of graft
      failure. It is conceivable, however, that it will never be possible to kill all
      leukemic cells with chemoradiotherapy of any form, and the graft-versus-leukemia
      effect may be essential. Perhaps in the future it will be possible to distinguish
      lymphocytes causing the graft-versus-leukemia effect from those causing GVHD,
      isolate them, and use them in attempts at therapy. In the meantime, postgrafting
      immunosuppressive drugs are used most frequently to prevent and treat GVHD, and
      steadily improving survival statistics can be expected.

PMID- 1999769
TI  - The biology and clinical applications of granulocyte-macrophage colony
      stimulating factor.
AB  - GM-CSF is a hematopoietic growth factor that regulates myeloid cell proliferation
      and maturation and enhances the function of terminally differentiated effector
      cells. Results of clinical trials with GM-CSF in a number of disease states
      suggest a potential role of this growth factor to stimulate hematopoiesis. Future
      use of GM-CSF will depend on further studies to optimize its therapeutic
      efficacy.

PMID- 1999770
TI  - Cytokines and T lymphocytes in pediatrics.

PMID- 1999771
TI  - The ontogeny of T lymphocyte maturation and function.

PMID- 1999772
TI  - Hypertension and the kidney.

PMID- 1999773
TI  - Apparent increase in the incidence of invasive group A beta-hemolytic
      streptococcal disease in children.
AB  - Recently, among adults, an increase in the incidence of invasive disease caused
      by group A beta-hemolytic streptococci (GABS) has been noted, as has the
      appearance of a severe illness called "toxic shock-like syndrome," also caused by
      GABS. We now report an apparent increase beginning in 1987 in the incidence of
      invasive disease caused by GABS in children. Among these patients the
      manifestations were varied. One child had signs and symptoms compatible with the
      streptococcal toxic shock-like syndrome. Among the GABS isolates from our
      patients, 8 (80%) of 10 evaluated for M-protein antigens were nontypeable.
      Further studies will be necessary to determine the relationship between serotypes
      and virulence of GABS. Physicians should be aware of the possibility of an
      increasing incidence of invasive GABS disease in children, as well as its
      manifestations, which may include toxic shock-like syndrome.

PMID- 1999774
TI  - Gastrointestinal dysfunction and disaccharide intolerance in children infected
      with human immunodeficiency virus.
AB  - Because gastrointestinal dysfunction is a major problem in children with human
      immunodeficiency virus (HIV) infection, we utilized breath hydrogen measurements
      to determine the relationship between disaccharide malabsorption and
      gastrointestinal dysfunction in HIV-infected children. We found a strong
      association between lactose intolerance and persistent diarrheal disease in this
      population (p less than 0.007, Mann-Whitney U test). We also found evidence of
      sucrose malabsorption and persistent diarrheal disease in three of the children.
      Extensive microbiologic evaluations failed to reveal an etiologic agent related
      to the occurrence of gastrointestinal symptoms. Our findings indicate that
      disaccharide intolerance is a common occurrence in HIV-infected children with
      persistent diarrheal disease. Careful attention to dietary intake may be required
      to ameliorate clinical symptoms and to maintain adequate nutrition.

PMID- 1999775
TI  - Immunogenicity of four Haemophilus influenzae type b conjugate vaccines in 17- to
      19-month-old children.
AB  - OBJECTIVE: To compare the immunogenicity of four Haemophilus influenzae type b
      (Hib) conjugate vaccines in different populations of 17- to 19-month-old children
      in the United States. DESIGN: Four immunogenicity trials with sera were assayed
      in one laboratory. Trials 1 and 2 each compared one vaccine in two regions, and
      trials 3 and 4 were randomized comparisons of multiple vaccines within a region.
      SUBJECTS: A convenience sample of 313 healthy children recruited from pediatric
      practices in Minneapolis, Minn., Dallas and Houston, Tex., and Sellersville, Pa.
      MEASUREMENTS AND RESULTS: Children with prevaccination antibody greater than 0.15
      microgram/ml showed higher antibody responses to vaccination than children with
      less than or equal to 0.15 microgram/ml (p less than 0.001). Among the former,
      there were no significant differences in antibody response to vaccination with
      the different conjugates within any of the trials. Among children with less than
      or equal to 0.15 microgram/ml of antibody before vaccination, there were no
      significant differences in the geometric mean antibody responses of children in
      trial 1 vaccinated with polyribosylribitol phosphate-diphtheria toxoid (PRP-D) in
      Dallas or in Minneapolis, or of children in trial 3 in Dallas randomly assigned
      to receive Hib oligosaccharide-CRM197 (HbOC) or PRP-D. In contrast, in trial 2,
      children given PRP-tetanus toxoid (PRP-T) in Pennsylvania had a significantly
      higher geometric mean antibody response than children given PRP-T in Houston
      (13.5 vs 3.0 micrograms/ml; p = 0.005). In trial 4 in Minneapolis, the geometric
      mean antibody response was highest in children randomly assigned to receive PRP
      outer membrane protein (OMP) (9.3 micrograms/ml), followed by PRP-D (5.0
      micrograms/ml) and HbOC (2.3 micrograms/ml) (PRP-OMP vs HbOC; p = 0.005). In all
      four trials, IgG1 responses predominated compared with IgG2 responses.
      CONCLUSIONS: All four conjugate vaccines are immunogenic in children 17 to 19
      months of age. However, the magnitude of the anticapsular antibody response
      varied by vaccine type, the level of antibody in prevaccination sera, and
      geographic location.

PMID- 1999776
TI  - High risk of recurrent stroke after discontinuance of five to twelve years of
      transfusion therapy in patients with sickle cell disease.
AB  - Although long-term transfusion therapy is at least 90% effective in preventing
      recurrent strokes after an initial cerebrovascular accident in patients with
      sickle cell disease, it is unknown how long transfusion therapy should be
      continued. To address this question, we prospectively discontinued transfusions
      in 10 patients with sickle cell disease whose median duration of transfusion
      therapy after an initial stroke was 9 1/2 years (range 5 to 12 years). Before the
      transfusions were discontinued, patients were examined by cerebral angiography,
      magnetic resonance imaging of the head, neuropsychologic testing,
      electroencephalography, and a complete neurologic examination. Within 12 months
      after transfusion therapy was stopped, 5 of 10 patients had had an ischemic
      event. Three events caused relatively mild deficits in the same areas as those
      originally affected. Two were associated with massive intracranial hemorrhage,
      including one on the contralateral side of original involvement. An additional
      patient died suddenly of unknown causes. Of the four remaining patients, three
      declined to resume transfusion and are relatively well at greater than or equal
      to 18 months after therapy was stopped. The studies performed before transfusions
      were stopped were not predictive of recurrent stroke. The risk of recurrent
      cerebrovascular accident in this group was significantly greater than the
      estimated risk of 10% in patients who are receiving long-term transfusion therapy
      (p = 0.002). This adverse outcome suggests that patients with sickle cell disease
      who have had a stroke must receive long-term transfusion indefinitely or a
      suitable therapeutic alternative must be devised.

PMID- 1999778
TI  - Is it correct to correct? Developmental milestones in 555 "normal" preterm
      infants compared with term infants.
AB  - To determine whether correction for preterm birth should be applied during
      developmental assessment, we conducted a prospective national survey of very
      premature infants (born at less than 32 weeks of gestation); neurodevelopment in
      the first 2 years was studied with the Dutch child health care developmental
      assessment. In 555 preterm children who had no evidence of handicap at 2 years of
      age, the age at which developmental milestones were reached was established. The
      results were compared with the results of the same assessment in Dutch children
      born at term. During the first year, the development of the very premature
      children equaled the development of normal children when full correction was
      applied. At 2 years of age, development was equal to or better than normal
      children's development without correction. We conclude that full correction for
      prematurity should be applied in the first year to avoid overreferral for
      developmental stimulation, whereas at 2 years of age correction is not necessary.

PMID- 1999777
TI  - Fundoplication and gastrostomy in familial dysautonomia.
AB  - Fundoplication with gastrostomy has become a frequent treatment for patients with
      familial dysautonomia, so we evaluated the use of both procedures in 65 patients.
      Although patients differed widely in presenting signs and age, from 5 weeks to 40
      years, gastroesophageal reflux was documented in 95% of patients by
      cineradiography or pH monitoring. Panendoscopy was a useful adjunct. Preoperative
      symptoms of gastroesophageal reflux included vomiting, respiratory infections,
      and exaggerated autonomic dysfunction. Severe oropharyngeal incoordination
      frequently coexisted and resulted in misdirected swallows with aspiration,
      dependence on gavage feedings, or poor weight gain and dehydration. Follow-up
      after surgical correction ranged from 3 months to 11 years; 55 patients (85%)
      were available for a 1-year postoperative assessment. We had no instances of
      surgical death. The long-term mortality rate was 14%, primarily related to severe
      preexisting respiratory disease. Beyond the first postoperative year, 30 patients
      had pneumonia attributed to continued aspiration, exacerbation of preexisting
      lung disease, or recurrence of gastroesophageal reflux. Of 11 patients who
      vomited postoperatively, six had recurrence of reflux. Recurrence of
      gastroesophageal reflux was documented in eight patients (12%), and we revised
      the fundoplication in three patients. The number of patients with cyclic crises
      was reduced from 18 to 7; retching replaced overt vomiting in all but two of
      these seven patients, neither of whom had recurrence of reflux. Because
      oropharyngeal incoordination was prominent, concomitant use of gastrostomy and an
      antireflux procedure was especially effective in the treatment of younger
      patients with familial dysautonomia, before the development of severe respiratory
      disease. Despite the development of severe morning nausea in 15 patients, the
      combination procedure resulted in significantly improved nutritional status,
      decreased vomiting, and decreased respiratory problems. Appropriate use of
      gastrostomy feedings also contributed to success of the operation. The generally
      good outcome of fundoplication with gastrostomy confirms the benefit of this
      procedure in familial dysautonomia.

PMID- 1999779
TI  - Increased blood requirements during long-term transfusion therapy for sickle cell
      disease.

PMID- 1999780
TI  - Cold water exposure and vaso-occlusive crises in sickle cell anemia.

PMID- 1999781
TI  - Transmission of human immunodeficiency virus infection by breast-feeding.

PMID- 1999783
TI  - Mental retardation in Turner syndrome.

PMID- 1999782
TI  - Colonic transepithelial potential difference in infants with cystic fibrosis.

PMID- 1999784
TI  - Neonatal lupus erythematosus simulating transient myasthenia gravis at
      presentation.

PMID- 1999785
TI  - Hyperargininemia: intellectual and motor improvement related to changes in
      biochemical data.

PMID- 1999786
TI  - Enterohepatic circulation of nonconjugated bilirubin in rats fed with human milk.
AB  - To test the hypothesis that enhanced intestinal absorption of bilirubin may
      contribute to prolonged nonconjugated hyperbilirubinemia in human milk-fed
      infants, we studied a cross-section of 36 healthy infants and mothers. Milk from
      mothers and serum from infants were collected at 16.3 +/- 2.4 days. Milk was
      studied for its effect on the absorption of bilirubin labeled with carbon 14 in
      rats and compared with buffer and iron-fortified infant formula (Similac With
      Iron). The percentage of a 1 mg bilirubin dose absorbed by the rat was 25.29 +/-
      4.0% when it was administered into the duodenum with buffer, 4.67 +/- 2.4% with
      Similac formula, and 7.7 +/- 2.9% with human milk. Linear regression analysis,
      using the infant's serum nonconjugated bilirubin level as the dependent variable
      and the percentage of (14C)bilirubin absorbed by the rat with the corresponding
      mother's milk as the independent variable, revealed a significant correlation (r
      = 0.40; p = 0.016). Inspection of the data suggested that absorptive
      permissiveness correlated closely with infant serum bilirubin values greater than
      24 mumol/L (1.4 mg/dl) (r = 0.55; p = 0.007), whereas in those with bilirubin
      values less than or equal to 24 mumol/L, there was no apparent correlation. Milk
      was also analyzed for beta-glucuronidase, nonesterified fatty acids, and the
      ability to inhibit glucuronosyltransferase activity of rat liver microsomes in
      vitro, none of which correlated with the infant's serum bilirubin. These data
      support the theory that enhanced intestinal absorption of bilirubin contributes
      to the jaundice associated with breast-feeding.

PMID- 1999787
TI  - Changes in cardiac function during extracorporeal membrane oxygenation for
      persistent pulmonary hypertension in the newborn infant.
AB  - The effects of extracorporeal membrane oxygenation (ECMO) on cardiac function and
      its determinants (preload, afterload, contractility, and heart rate) are largely
      unknown, although some evidence exists that function may decrease. To determine
      whether cardiac function decreases and what changes in the determinants take
      place during and after ECMO, we observed 26 newborn infants with persistent
      pulmonary hypertension. Serial echocardiograms were performed before ECMO, during
      maximum cardiopulmonary bypass, and after ECMO. Cardiac function was assessed by
      using standard echographic ejection phase indices (shortening fraction and
      cardiac output). Heart rate, preload (left ventricular end-diastolic dimension
      and area), afterload (left ventricular end-systolic wall stress), and
      contractility (relationship between velocity of circumferential fiber shortening
      and wall stress) were also measured. Ejection phase indices significantly
      decreased during ECMO (shortening fraction 33% to 25%, cardiac output 205 to 113
      ml/kg/min; p less than 0.05) and returned to normal after ECMO (shortening
      fraction 26% to 34%, cardiac output 107 to 240 ml/kg/per minute; p less than
      0.05). Heart rate also significantly decreased during ECMO (158 to 118 beats/min;
      p less than 0.05). Preload significantly increased after ECMO (left ventricular
      end-diastolic dimension 1.4 to 1.6 cm, left ventricular end-diastolic area 1.9 to
      2.2 cm2; p less than 0.05). There were no significant changes in contractility
      and afterload during any study period. We conclude that, although left
      ventricular ejection phase indices and heart rate decreased during ECMO, these
      changes were transient and resolved when bypass was terminated. Contractility and
      afterload did not appear affected by bypass.

PMID- 1999788
TI  - Cardiac performance in infants referred for extracorporeal membrane oxygenation.
AB  - We performed cardiac evaluations in 59 infants referred for severe lung disease
      to determine whether cardiac performance was impaired in those requiring
      extracorporeal membrane oxygenation (ECMO). Infants were divided into two groups:
      group 1 (n = 25) received conventional therapy and group 2 (n = 34) received ECMO
      therapy after meeting established criteria. Ventilatory and oxygenation indexes
      and estimates of right ventricular systolic pressure were measured. Load
      dependent and load-independent echocardiographic indexes of cardiac performance
      were also measured. The infants in the two groups had similar diagnoses, age,
      weight, inotropic support, ventilator and oxygenation indexes on admission, and
      survival. Heart rate and estimates of preload and afterload were similar in the
      two groups. Ventricular shortening fraction was 36.1 +/- 7.6% in group 1 and 40.5
      +/- 8.8% in group 2 (p value was not significant). Velocity of circumferential
      fiber shortening (VCF/sec) was 1.41 +/- 0.35 in group 1 and 1.58 +/- 0.39 in
      group 2 (p value was not significant). The relationship between wall stress and
      ventricular shortening was similar in the two groups. There were no differences
      in cardiac output. Pulmonary artery pressure was estimated to be 56 +/- 13 mm Hg
      in group 1 and 63 +/- 10 mm Hg in group 2 (p = 0.017). Thus no significant
      differences were found in load-dependent or load-independent measures of cardiac
      performance in infants with severe lung disease treated with ECMO or conventional
      therapy. We conclude that cardiac failure is not the primary cause of clinical
      deterioration in infants with severe lung disease who require ECMO therapy.

PMID- 1999789
TI  - Airway responsiveness to low inspired gas temperature in preterm neonates.

PMID- 1999790
TI  - Postural effects on pulmonary function and heart rate of preterm infants with
      lung disease.

PMID- 1999791
TI  - Effect of therapeutic plasma concentrations of theophylline on behavior,
      cognitive processing, and affect in children with asthma.
AB  - A double-blind, randomized, crossover study assessed the effects of theophylline
      on behavior, mood, and efficiency of cognitive processing. Thirty-one children
      aged 8 to 12 years with moderate asthma were randomly assigned to 10-day
      theophylline followed by placebo or to placebo followed by theophylline
      experimental conditions separated by 2-day washout periods. Theophylline plasma
      concentrations and pulmonary function tests were performed throughout the study.
      Cognitive functioning tests and self-report measures were administered at
      baseline and after each medication phase. Behavior ratings were obtained from
      parents and teachers. Parents' and teachers' ratings did not reflect a
      theophylline effect on attention or activity level; children's self-reports
      showed no changes in mood, and no statistically significant differences were
      found on measures of cognitive processing. Large individual differences in
      sensitivity to theophylline effects were present. Although most of the children
      tolerated theophylline well, those already having attentional or achievement
      problems appeared vulnerable to adverse effects. Individual response differences
      should be a focus of future studies.

PMID- 1999792
TI  - Decreased protein binding of salicylates in Kawasaki disease.
AB  - Because patients with Kawasaki disease have low serum concentrations of
      salicylates despite high doses, and because the free (unbound) drug is
      responsible for the pharmacologic effects of salicylates, we assessed salicylate
      protein binding in patients with Kawasaki disease. During the acute phase of the
      disease, protein binding of salicylate in 36 children with Kawasaki disease was
      73 +/- 12%, significantly lower than during the subacute phase (90.4 +/- 8.7%; p
      less than 0.0005). Mean serum albumin concentration was 29.2 +/- 6.4 gm/L during
      the acute phase and 36.7 +/- 7.8 gm/L during the subsequent subacute phase (p
      less than 0.005). Salicylate protein binding was affected independently by both
      serum albumin and total salicylate levels. During the acute phase of Kawasaki
      disease, children had an average twofold increase in free salicylate compared
      with normoalbuminemic control subjects. A nomogram has been devised to derive
      free salicylate levels from the known total salicylate and serum albumin
      concentrations.

PMID- 1999793
TI  - Patient-controlled analgesia in children and adolescents: a randomized,
      prospective comparison with intramuscular administration of morphine for
      postoperative analgesia.
AB  - A randomized, prospective trial of patient-controlled analgesia (PCA), that is, a
      method of analgesia administration involving a computer-driven pump activated by
      patients to receive small doses within defined limits was performed in 82
      children and adolescents after major orthopedic surgery to compare (1)
      intramuscularly administered morphine, (2) PCA morphine and (3) PCA morphine with
      a low-dose continuous morphine infusion (PCA-plus). Patients receiving PCA and
      PCA-plus had lower pain scores and greater satisfaction than patients receiving
      intramuscularly administered morphine. The three groups used equal amounts of
      morphine and most measures of recovery were identical in the groups. In
      particular, PCA and PCA-plus did not increase the incidence of opioid-related
      complications, and patients receiving PCA-plus were less sedated than patients
      receiving intramuscular therapy. We conclude that PCA and PCA-plus are safe and
      effective methods of pain relief in children and adolescents after orthopedic
      surgery, are better accepted than intramuscular injections, and do not increase
      perioperative morbidity.

PMID- 1999794
TI  - Relationships of somatic symptoms to behavioral and emotional risk in young
      adolescents.
AB  - Junior high students (n = 1508) from a midwestern community completed a health
      behavioral questionnaire that asked the frequency of headache and abdominal pain
      and of a number of behavioral and emotional risk indicators. Headache (24%) and
      abdominal pain (13%) were frequently reported among these young adolescents,
      particularly among girls. Those reporting frequent somatic complaints also
      reported significantly more behavioral and emotional symptoms indicative of risk
      (p less than 0.001). Further, the interaction between somatic complaint and
      gender significantly affected risk status (p less than 0.01). This interaction
      was greater with behavioral risk: boys with both abdominal pain and headaches
      reported higher behavioral risk than all other groups (p less than 0.0001).
      Somatic symptoms continued to account for a significant amount of variance in
      behavioral risk after the effects of emotional risk and age were removed. This
      suggests that behavioral risk and emotional risk are independently associated
      with somatic complaints. The evaluation of persistent somatic complaints in
      adolescents, particularly in boys with abdominal symptoms, should include careful
      examination of emotional risk factors and other health-endangering behaviors such
      as substance use, early sexual activity, and delinquency.

PMID- 1999795
TI  - Progressive hypertension associated with hypokalemic alkalosis.

PMID- 1999797
TI  - Disordered sleep, daytime vigilance, and attention deficit hyperactivity
      disorder.

PMID- 1999796
TI  - Association of rug shampooing and Kawasaki disease.

PMID- 1999798
TI  - Early identification of human immunodeficiency virus infection in infants.

PMID- 1999799
TI  - Allergy: an alternative explanation for brain injury by pertussis vaccine.

PMID- 1999800
TI  - Normal digital pressure changes following the postocclusive reactive hyperemia
      test.
AB  - The authors report digital pressure changes in normal subjects following the 5
      min postocclusive reactive hyperemia test. This test increases the sensitivity of
      using toe pressures to assess the adequacy of blood flow.

PMID- 1999801
TI  - Heel spur syndrome. Pathomechanics and nonsurgical treatment. Biomechanics
      Graduate Research Group for 1988.
AB  - In this study, the authors review the multitude of suspected etiologies of heel
      spur syndrome, propose a new pathomechanical theory, and apply a treatment plan
      to 84 patients with 133 painful heels. The study investigates whether there is a
      common foot type to the syndrome and whether factors such as sex, age,
      occupation, and weight influence incidence or treatment. A subgroup is
      established, consisting of subjects who only received mechanical treatment, to
      determine if a change in foot position can relieve symptoms.

PMID- 1999803
TI  - Evaluation of recurrent macrodactyly with three-dimensional imaging.
AB  - Macrodactyly is a deformity that may progress beyond initial surgical resection.
      Three-dimensional computed tomography imaging may aid in the surgical planning,
      given the osseous irregularities that may exist. The objective in revisional
      surgery of this type is to provide the most functional and cosmetic result. In
      this case, the hallux was saved when the patient previously had requested an
      amputation. The case also illustrates that when earlier surgery has been
      performed, the classic approaches to macrodactyly advocated in the literature may
      not be feasible. The surgeon must then approach the deformity with some
      flexibility, and three-dimensional imaging may be a useful tool.

PMID- 1999802
TI  - A study of the properties of materials used in podiatry.
AB  - This study was performed to provide insight into the functioning of a selection
      of materials used in the fabrication of orthoses. A series of mechanical and
      physical tests was performed on five materials, under strict laboratory
      conditions. The results demonstrate that the polyurethane foams are the most
      promising material in the design of foot orthoses. The results also suggest that
      an agglomeration of properties, not just one specific property, can influence the
      behavior of materials.

PMID- 1999805
TI  - Research process. Reporting results of the research.
AB  - The preparation of a manuscript to report a research project is the final stage
      of the research process. Recommendations are made in this article related to
      preparing to write, getting started, guarding against problems and frustrations
      by making early decisions, and developing each component of the manuscript. This
      article is the last in a series of six on the research process, in which the
      collective purpose has been to offer guidance regarding the spectrum of skills
      required to produce quality research reports.

PMID- 1999804
TI  - Calcanectomy for the treatment of calcaneal osteomyelitis. A case report.

PMID- 1999806
TI  - Podiatry is born.

PMID- 1999807
TI  - Myxoedema: some early reports and contributions by British authors, 1873-1898.

PMID- 1999808
TI  - The legacy of Henry Head.

PMID- 1999809
TI  - George Walton MB DPH 1887-1963: prairie physician-poet.

PMID- 1999811
TI  - Thoracic endoscopic sympathectomy for palmar hyperhidrosis in an adolescent
      female.

PMID- 1999810
TI  - Small left colon syndrome: an immature enteric plexus.

PMID- 1999812
TI  - Guillain-Barre syndrome following severe exertion.

PMID- 1999813
TI  - A report--chronic fatigue syndrome: guidelines for research.

PMID- 1999814
TI  - The homeopathic conundrum.

PMID- 1999815
TI  - Advanced medical courses at the Royal Society of Medicine.

PMID- 1999816
TI  - Instrumental dilation of the uterine cervix in antiquity--a myth or not?

PMID- 1999817
TI  - The Norman Tanner Medal of the Royal Society of Medicine Section of Surgery.

PMID- 1999818
TI  - The plain radiograph in ophthalmology: a wasteful and potentially dangerous
      anachronism.
AB  - The indications for 822 consecutive referrals for skull radiography were
      prospectively studied in a large eye hospital over a one year period. In 85.9% of
      patients the results were normal, and in 89% of the remainder they had no
      positive effects on management; all patients in whom a 'beneficial' effect could
      be identified would have been more appropriately investigated by other means.
      Fourteen of 25 patients whose skull radiographs were normal were shown by
      computed tomography or magnetic resonance imaging to have orbital or intracranial
      lesions. Views of the optic canals, orbits or paranasal sinuses were also
      requested in 336 patients. With appropriate use of alternative imaging methods,
      no patient's treatment would have been adversely affected if none of the skull
      radiographs had been obtained.

PMID- 1999819
TI  - A camera that directly measures physical parameters.
AB  - Accurate measurement of physical parameters is essential for the practice of
      modern medicine and ophthalmology in particular. A measuring device is presented
      that combines a single lens reflex (SLR) camera body incorporating two aligned in
      camera grids with a calibrated macrozoom attachment. The device has multiple
      applications wherever accurate measurements are required. The ability to measure
      and record physical parameters in both health and disease is essential to modern
      medical practice. This is particularly so in ophthalmology. Despite the relative
      accessibility of external structures, the clinician's measuring equipment often
      takes the form of a clear plastic ruler with the ever present possibility of
      inaccuracy from parallax and perspective. Indeed, even in the hands of expert
      observers, the results from the commercially produced Hertel exophthalmometer are
      prone to significant variation. Various photographic methods of measurement have
      been described using a fixed focal length lens system, and recently evaluated.
      These, however, require processing of the photographs before measurements can be
      taken. We present a simple, relatively inexpensive multi-purpose device which can
      measure physical parameters directly and record photographic evidence of these
      measurements. In essence, the device consists of a single lens reflex (SLR)
      camera fitted with two carefully aligned grids, linked to a calibrated macrozoom
      lens.

PMID- 1999820
TI  - Adenocarcinoma of the gallbladder--a 5 year review of outcome in Newcastle upon
      Tyne.
AB  - Patients presenting with adenocarcinoma of the gallbladder within Newcastle upon
      Tyne over a 5 year period (1980-1985) were reviewed retrospectively. The mean age
      of patients on diagnosis was 74 years. Of the 29 patients diagnosed, two were
      detected after routine cholecystectomy. Laparotomy was performed in 21 patients
      (72%) of which only 14 patients had a cholecystectomy performed. Mean survival
      after surgery was 6.6 months with only one patient alive after 5 years.
      Metastatic disease was present in 72% of patients. The poor prognosis of
      carcinoma of the gallbladder reflects its late diagnosis and early metastasis to
      distant sites. Improvement in survival will depend upon early detection of in
      situ lesions and identification of at risk patients.

PMID- 1999821
TI  - Persistent ulceration of the anal margin in homosexuals with HIV infection.
AB  - A study of the outcome of surgical treatment of ulceration of the anal margin
      occurring in male homosexuals with HIV infection was undertaken. Ten patients
      with acquired immunodeficiency syndrome and three patients with symptomatic HIV
      infection were referred to the Department of Surgery with painful anal ulceration
      which had not responded to medical treatment. The medical treatments given prior
      to surgical referral included high dose oral acyclovir, intravenous foscarnet and
      broad spectrum antibiotics. Excision biopsy was performed in 12 patients and in
      11 cases was followed by healing of the ulcers within 10 weeks. One patient died
      2 weeks postoperatively from Pneumocystis carinii pneumonia without healing. The
      response to excision biopsy was unexpected but suggests that surgical excision
      may be beneficial for lesions which have failed to respond to aggressive medical
      treatment.

PMID- 1999822
TI  - A psychiatric presentation of abulia--three cases of left frontal lobe ischaemia
      and atrophy.

PMID- 1999823
TI  - Changing concepts of oral epithelium: discussion paper.

PMID- 1999824
TI  - The war on cancer--failure of therapy and research: discussion paper.

PMID- 1999825
TI  - The 1978 Italian mental health law--a personal evaluation: a review.
AB  - The author discusses the sociopsychiatric consequences of the 1978 Italian mental
      health law. He also reviews the international scientific ideas that led up to it.
      The sociopolitical psychiatric views of the late Franco Basaglia, pioneer of the
      change in the mental health system of the Italian Republic, are described.
      Statistical reports and critical analyses are reported. Objective data, based on
      the author's personal experience as a practising psychiatrist in Rome, Italy,
      from 1969 to 1987, are given.

PMID- 1999826
TI  - Hereditary motor and sensory neuropathies.

PMID- 1999828
TI  - Oculofacialbulbar palsy in mother and son: review of 26 reports of familial
      transmission within the 'Mobius spectrum of defects'.
AB  - We report a mother and son with 5th, 6th, 7th, and bulbar cranial nerve
      paralysis, who had two similarly affected relatives. None of them had primary
      skeletal defects. Twenty-six previous reports of familial cases within the
      heterogeneous 'Mobius spectrum of defects' were reviewed. When cranial nerve
      palsies were associated with a primary skeletal defect, familial transmission was
      not found. No recurrence was noted in 31 cases with cranial nerve palsies
      associated with oral abnormalities and limb defects. The term Mobius syndrome
      should be restricted to cases with congenital 6th and 7th nerve paralysis with
      skeletal defects, who have a low recurrence risk (2%). The features in an index
      case which may indicate a higher risk of recurrence are the absence of skeletal
      defects, isolated facial palsy, deafness, ophthalmoplegia, and digital
      contractures. A recurrence risk of 25 to 30% in these cases appears reasonable.

PMID- 1999827
TI  - Short stature/short limb skeletal dysplasia with severe combined immunodeficiency
      and bowing of the femora: report of two patients and review.
AB  - We report two patients with severe combined immunodeficiency and short
      stature/short limb skeletal dysplasia. Case 1 presented at birth with rhizomelic
      shortening of the extremities and bowing of the femora. She developed clinical
      signs of severe combined immunodeficiency at 13 months and died at 21 months.
      Case 2 had severe prenatal shortening and bowing of the extremities and a small,
      malformed chest. Symptoms of severe combined immunodeficiency and severe failure
      to thrive developed soon after birth and she died at 5 months. The diagnosis of
      severe combined immunodeficiency in our patients was based on their clinical
      course and necropsy findings, supported in case 1 by the results of immune
      function tests. The results of investigation of immune function (immunoglobulins,
      lymphocyte subpopulations, lymphocyte function) are very variable in this
      syndrome as in other variants of severe combined immunodeficiency. Bone
      histopathology in both patients showed grossly irregular costochondral junctions,
      but normal transition of proliferating to hypertrophic chondrocytes. These cases
      belong to early lethal type 1 short limb skeletal dysplasia with severe combined
      immunodeficiency. Review of previously published cases with severe combined
      immunodeficiency and well documented skeletal findings show eight patients with
      prenatal onset of bowing and shortening of the extremities and metaphyseal
      abnormalities. These include two sib pairs concordant for the skeletal changes.
      In these cases, adenosine deaminase levels were not reported. An additional four
      published cases with associated adenosine deaminase deficiency had only mild
      metaphyseal abnormalities, but subsequently showed no linear growth.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1999829
TI  - Evidence for variable gene expression in a large inbred kindred with autosomal
      recessive spondylocostal dysostosis.
AB  - Seven members of a large inbred kindred with autosomal recessive spondylocostal
      dysostosis were examined clinically, radiographically, and sonographically. The
      subjects were three adults, one adolescent, and three children under 3 years of
      age. One child was the offspring of a first cousin marriage which showed quasi
      dominant inheritance. Six subjects had short stature owing to widespread
      vertebral dyssegmentation with variable reduction in rib number and rib fusion.
      One subject was of normal stature, had limited vertebral dyssegmentation, an
      extra rib, and no rib fusion. Five subjects showed the plagiocephaly-torticollis
      sequence. Four of the five male subjects had inguinal herniation on one or both
      sides. All subjects had normal renal ultrasonography. The youngest subject died
      of cardiopulmonary complications and is thought to represent one extreme in the
      expressivity of the gene in this kindred.

PMID- 1999830
TI  - Association of less common cystic fibrosis mutations with a mild phenotype.
AB  - A majority of cystic fibrosis (CF) genes (70 to 75%) share a single mutation, but
      the remaining 25 to 30% of defects are accounted for by more than 20 different
      mutations. One of the less frequent mutations, G551D, has been identified in the
      CF genes of two sibs and one unrelated adult patient. The adult patient also has
      a second rare mutation, delta I507. All three subjects exhibit a less severe
      phenotype than that normally associated with CF. This supports a hypothesis that
      the common mutation (delta F508) is responsible for the severe form of the
      disorder, and the minority of patients with a milder form tend to have mutations
      at other sites in the CF gene.

PMID- 1999831
TI  - The sex ratios of probands and of secondary cases in conditions of multifactorial
      inheritance where liability varies with sex.
AB  - Some pathological conditions affect one sex more often than the other. A curious
      feature of some of these conditions (dyslexia, congenital dislocation of the hip,
      pyloric stenosis, otosclerosis, lupus erythematosus, ankylosing spondylitis) is
      that the sex ratio (proportion of males) of randomly ascertained probands is more
      extreme than that of their affected relatives. In all these conditions,
      multifactorial inheritance has been suspected. A simple model is offered here of
      multifactorial inheritance with liability varying by sex. Under the model, such a
      disparity between sex ratios would be expected.

PMID- 1999832
TI  - Aarskog syndrome.

PMID- 1999833
TI  - Growth hormone deficiency in a girl with the Cohen syndrome.
AB  - A girl with the Cohen syndrome and isolated growth hormone deficiency is
      described. Treatment with biosynthetic human growth hormone resulted in marked
      catch up growth to normal stature. It is concluded that growth hormone deficiency
      should be ruled out in patients with the Cohen syndrome and small stature.

PMID- 1999834
TI  - Spondylocostal dysplasia and neural tube defects.
AB  - Spondylocostal dysplasia (Jarcho-Levin syndrome) comprises multiple malformations
      of the vertebrae and ribs coupled with a characteristic clinical picture of short
      neck, scoliosis, short trunk, and deformity of the rib cage. We describe a
      patient with the syndrome who also had spina bifida and diastematomyelia. We
      surmise that this association is not coincidental. Additional evidence is needed
      to support the hypothesis that spondylocostal dysplasia and neural tube defects
      are aetiologically related.

PMID- 1999835
TI  - Balanced t(6;8)(6p8p;6q8q) and the CHARGE association.
AB  - A girl is described with bilateral retinal colobomata, Fallot's tetralogy,
      unilateral choanal atresia, abnormalities of the external ears, bilateral
      sensorineural deafness, a unilateral facial nerve palsy, and a tracheo
      oesophageal fistula. A clinical diagnosis of the CHARGE association was made. She
      had an apparently balanced whole arm translocation involving chromosomes 6 and 8.
      Parental karyotypes were normal.

PMID- 1999836
TI  - Unknown syndrome: ischiadic hypoplasia, renal dysfunction, immunodeficiency, and
      a pattern of minor congenital anomalies.
AB  - We report a 6 year old male with a pattern of malformations and anomalies
      including intrauterine growth retardation, microcephaly, psychomotor retardation,
      a pattern of craniofacial anomalies (flat face, hypertelorism, epicanthic folds,
      strabismus, short nose, low set ears), hypospadias and cryptorchidism, bilateral
      partial cutaneous syndactyly between fingers 2 to 5 and toes 2 to 4, postaxial
      polydactyly of the fingers and toes, severe conductive hearing loss, hypoplasia
      of the ischiadic bones, complex renal dysfunction, hypogammaglobulinaemia with
      proneness to bacterial infections of the upper and lower respiratory tract, and
      recurrent pseudomembranous enterocolitis. The parents are cousins of Turkish
      origin.

PMID- 1999837
TI  - An investigation of ring and dicentric chromosomes found in three Turner's
      syndrome patients using DNA analysis and in situ hybridisation with X and Y
      chromosome specific probes.
AB  - We have studied three patients with features of Turner's syndrome, two with a
      45,X/46,X,r(?) and the third with a 45,X/46,X,dic?(Y) karyotype. Because Turner's
      syndrome patients with a mosaic karyotype containing a Y chromosome are known to
      have a high risk of developing gonadal tumours, we used DNA analysis and in situ
      hybridisation with X and Y specific probes to identify the chromosomal origin of
      the rings and dicentric chromosomes in the three index patients. Both ring
      chromosomes were shown to be of X origin, while the dicentric was composed of Y
      chromosome material. We discuss the importance of using a combination of
      molecular and cytogenetic analyses in such cases.

PMID- 1999838
TI  - A familial case of chromosome 16p variant.

PMID- 1999839
TI  - Facial measurements in the newborn.

PMID- 1999840
TI  - Rickettsiae-like structures in the larval salivary gland cells of Drosophila
      auraria.
AB  - Rickettsiae-like structures were found in the salivary gland cells of Drosophila
      auraria during different larval and prepupal developmental stages, from the early
      3rd instar up to 14 hr after spiracle inversion. These microorganisms are
      surrounded by a membrane, are constantly intracellular, and occur singly or in
      groups. Their widespread occurrence in various tissues of other Drosophila
      species indicates that they can be considered as symbionts, but their actual
      functional significance (if any) is unknown.

PMID- 1999841
TI  - Ultrastructure of Mehlis' gland in the lung fluke, Paragonimus ohirai (Trematoda:
      Troglotrematidae).
AB  - Mehlis' gland of a digenetic trematode, Paragonimus ohirai, is composed of two
      types of secretory cells, DB and CB. The less abundant type (DB) produces dense
      bodies, with the cytoplasm characterized by greatly distended cisternae of rough
      endoplasmic reticulum. The other type (CB) synthesizes clear, vesicular bodies.
      Its cytoplasm contains numerous mitochondria, rough endoplasmic reticulum with
      narrow cisternae, and abundant Golgi complexes. Processes of the two cell types
      converge on the ootype-proximal uterine wall, pass through the epithelium, and
      finally open into the lumen. These proximal processes contain longitudinally
      arranged microtubules whose luminal ends are anchored to the epithelium by ring
      form septate desmosomes. According to the distribution of the two types of
      processes, three different zones (DB, mixed, and CB) can be recognized within the
      epithelia. As the CB processes enter the lumen predominantly beyond the uterine
      valve region, this cell may produce secretions required for egg shell maturation
      or hardening. The role of DB cells (which enter the lumen more commonly in the
      ootype near the oviduct) remains unknown.

PMID- 1999842
TI  - Problems in cancer surveillance: delineating in situ and invasive bladder cancer.

PMID- 1999843
TI  - Combined treatment substantially improves outlook for rectal cancer patients.

PMID- 1999844
TI  - Twenty years of progress in immunology research is ready for harvest.

PMID- 1999845
TI  - Hazards of handling chemotherapeutic agents known but not heeded.

PMID- 1999846
TI  - Vitamin C: how it may protect against cancer is unclear.

PMID- 1999847
TI  - Immunology of cutaneous T-cell lymphoma.

PMID- 1999848
TI  - Endometrial cancer: biochemical and clinical correlates.
AB  - Some endometrial cancers and endometrial adenocarcinoma cell lines show amplified
      expression of proto-oncogenes (fos, fms, myc, myb, neu, and erb-B) and augmented
      production of growth factors (colony-stimulating factor 1, epidermal growth
      factor, transforming growth factor-alpha, and transforming growth factor beta)
      and epidermal growth factor receptor. Oncogene expression, the presence of
      estrogen and progesterone receptors, and the fraction of cells in S phase are
      useful biochemical prognostic indicators of clinical outcome, and markers
      recognized by monoclonal antibodies are available for use in following the
      clinical course of the disease and responses to treatment. In vivo and in vitro
      studies on normal and neoplastic tissues are providing evidence of paracrine
      influences on epithelial cell proliferation. Long-term administration of
      tamoxifen as adjuvant therapy for breast cancer has recently been found to
      increase the risk for development of endometrial cancer.

PMID- 1999849
TI  - Cancer registry problems in classifying invasive bladder cancer.
AB  - A slide review of diagnostic pathologic tissue obtained from 364 bladder cancer
      cases, identified through the Iowa Surveillance, Epidemiology, and End Results
      (SEER) Program in 1983, classified 97 (26.6%) of these cases as invasive bladder
      cancers. These findings contrasted sharply with the Iowa SEER Program
      classification that coded 289 (79.4%) of these cases as invasive bladder cancers.
      These results were validated further by the hazard ratio of 4.54 (95% confidence
      interval, 2.57 to 8.03) among invasive relative to noninvasive bladder cancer
      cases when the slide review findings were used. In contrast, the hazard ratio was
      only 1.70 (95% confidence interval, 0.76 to 3.79) when the Iowa SEER Program
      findings were used. The traditional method used by the National Cancer
      Institute's SEER Program to deal with this problem is described and its
      implications are discussed.

PMID- 1999850
TI  - Preferential localization of human adherent lymphokine-activated killer cells in
      tumor microcirculation.
AB  - The efficacy of adoptive immunotherapy for solid tumors with lymphokine-activated
      effector cells presumably depends on the ability of these cells to localize
      adequately in tumor tissues. We present here the first quantitative study of the
      in vivo movement of fluorescently labeled adherent lymphokine-activated killer (A
      LAK) cells. These cells were injected intra-arterially along with low-dose
      interleukin-2 into normal (mature granulation) tissue and an implant of VX2
      carcinoma grown in the rabbit ear chamber. A small proportion of A-LAK cells
      accumulated preferentially in the tumor microcirculation in vivo because of an
      increased frequency of long-term adhesive interactions with the tumor
      vasculature. Stasis of blood flow in the tumor vasculature was observed 1 to 2
      days after injection. Subsequent necrosis of the tumors was observed, along with
      diffuse infiltrates of lymphocytes, monocytes, and granulocytes in the
      interstitial space within the tumor. Development of necrosis despite low ratios
      of effector cells to target cells suggests that in addition to direct
      cytotoxicity, the response to adoptive immunotherapy is mediated via the tumor
      vasculature. This novel mechanism for adoptive immunotherapy must be taken into
      account in the development of improved strategies for cancer treatment.

PMID- 1999851
TI  - Clinical and pharmacologic study of orally administered uridine.
AB  - Effects of oral administrations of uridine were investigated in a study of six
      healthy volunteer control subjects and nine patients with metastatic colorectal
      cancer. Oral uridine was studied as single-dose administrations at doses
      escalating from 0.3 to 12 g/m2 and as multiple-dose administrations every 6 hours
      for 3 days at doses from 5 to 10 g/m2. The maximum tolerated dose (MTD) was 10 to
      12 g/m2 for a single dose of uridine and 5 g/m2 for the multiple-dose regimen.
      Diarrhea was the dose-limiting toxic effect. Single-dose oral uridine resulted in
      an increase in plasma uridine concentrations in the range of 60 to 80 microM
      after doses of 8 to 12 g/m2. At these doses, bioavailability of oral uridine
      ranged from 5.8% to 9.9%. At the MTD of 5 g/m2 in the multiple-dose uridine
      schedule, steady-state plasma uridine levels of approximately 50 microM were
      achieved. Further studies should explore the role of oral uridine in the
      modulation of the toxicity of fluorouracil.

PMID- 1999852
TI  - Metastatic breast cancer in a young patient seropositive for human
      immunodeficiency virus.

PMID- 1999853
TI  - Treatment of cancer anorexia with megestrol acetate: which is the optimal dose?

PMID- 1999854
TI  - Influence of preservation or perfusion of intraoperatively identified spinal cord
      blood supply on spinal motor evoked potentials and paraplegia after aortic
      surgery.
AB  - Permanent ligation of arteries supplying blood to the spinal cord in operations
      for aortic aneurysm can lead to spinal cord ischemia, which can result in either
      paraparesis or paraplegia. This report describes a rapid method of intraoperative
      identification of those arteries that supply the spinal cord by use of an
      intrathecal platinum electrode to detect hydrogen in solution that has been
      injected into the aortic ostia. Preservation or perfusion of those identified
      arteries supplying the spinal cord may decrease the rate of postoperative
      neurologic complications. Of 28 porcine experiments with postoperative
      observation for 24 hours, there were 3 initial pilot experiments in which saline
      saturated with hydrogen was injected into the temporarily cross-clamped aorta.
      Twenty animals were then randomized to (1) preservation of only the vessels
      sequentially identified to supply blood to the spinal cord from T-13 to L-5 (n =
      10); (2) division of the vessels supplying the spinal cord (n = 10). A further
      five animals underwent perfusion experiments wherein the identified cord arteries
      were perfused by a shunt, the other nonsupply arteries were divided, and the
      aorta was kept clamped for 45 minutes. Spinal motor evoked potentials were
      elicited with an intrathecal electrode and were highly sensitive for paralysis.
      Paralysis occurred in 0/3 pilot (p less than 0.013 vs division); 8/10 division;
      1/10 preservation (p less than 0.0017 vs division); and perfusion 1/5 (p less
      than 0.025 vs division). Results of a pilot study in eight humans shows that the
      technique can be used to rapidly identify segmental arteries supplying the spinal
      cord, to determine if distal perfusion is supplying the spinal cord with blood
      flow, and if reattached segmental arteries are patent.

PMID- 1999855
TI  - Abdominal aortic aneurysm: results of a family study.
AB  - Data pertaining to abdominal aortic aneurysm among first-degree relatives of 91
      patients with abdominal aortic aneurysm are presented. The percentage of families
      with at least one affected first-degree relative of the proband (multiplex
      families) was 15.4%. In 21.4% of multiplex families parent-offspring transmission
      of abdominal aortic aneurysm was noted; in the remaining families only siblings
      were affected. The mean age at onset among probands was 67.3 years; that among
      all affected was 67.4 years. No statistically significant difference in the mean
      ages at onset between genders was noted. Among affected siblings of probands, the
      sex ratio, male:female, was 1.33:1, which is not significantly different from
      1:1. The relative risk of developing an abdominal aortic aneurysm was 3.97 for
      fathers, 4.03 for mothers, 9.92 for brothers, and 22.93 for sisters.

PMID- 1999856
TI  - Cells derived from omental fat tissue and used for seeding vascular prostheses
      are not endothelial in origin. A study on the origin of epitheloid cells derived
      from omentum.
AB  - The use of microvascular endothelial cells derived from omental tissue has been
      advocated to seed vascular grafts with autologous endothelial cells in high
      density. The purpose of our study was to evaluate the precise origin of these
      cells. Therefore we have compared cellular characteristics of these cells with
      those of endothelial cells isolated by collagenase treatment of human umbilical
      veins. The omental cells were isolated from from omental tissue from four
      different patients by incubation in a collagenase-dispase solution. Part of the
      material was processed by Percoll density gradient centrifugation in an attempt
      to purify the isolates. Cellular characteristics of both types of cells were
      determined by studying the morphologic features of the cells and by determining
      the presence of von Willebrand factor, antigens EN-4 and PAL-E specific for
      endothelial cells, cytokeratins 8 and 18, vimentin and desmin, and uptake of diI
      acetylated low-density lipoprotein. Epitheloid cells from omental tissue,
      isolated after collagenase treatment and either purified or nonpurified by
      Percoll density gradient centrifugation, differed from human umbilical vein
      endothelial cells with respect to the presence of surface microvilli, the
      expression of von Willebrand factor, EN-4 and PAL-E, and the presence of
      cytokeratins 8 and 18 and desmin. von Willebrand factor (in a granular staining
      pattern) and the presence of EN-4 and PAL-E were only detected in human umbilical
      vein endothelial cells. Vimentin was present in both cell types, whereas
      cytokeratins 8 and 18 and desmin were only present in cells derived from omentum.
      From these data we conclude that the so called microvascular endothelial cells
      from omentum are not endothelial but mesothelial in nature.

PMID- 1999857
TI  - Subclavian artery to innominate vein fistula after insertion of a hemodialysis
      catheter.
AB  - Insertion of hemodialysis catheters for temporary use is now preferentially
      performed by percutaneous infraclavicular subclavian vein catheterization. This
      method involves passage of a stiff dilator and a peel-away sheath over a guide
      wire, and is usually carried out without fluoroscopy. For the most part this has
      proved to be a valuable and safe approach. However, a small incidence of major
      complications occurs, which needs to be emphasized. Sixteen cases of
      arteriovenous fistulas between the subclavian artery or its branches and the
      subclavian vein have been reported so far in the literature. To date only one
      case of subclavian artery to innominate vein fistula has been reported. We report
      the second case with this complication and suggest possible preventive measures.

PMID- 1999858
TI  - Limitations of magnetic resonance imaging and ultrasound-directed (duplex)
      scanning in the diagnosis of subclavian vein thrombosis.
AB  - To investigate the potential role of magnetic resonance imaging and duplex
      scanning in the diagnosis of catheter-induced subclavian vein thrombosis, we
      correlated the results of 43 arm phlebograms with duplex scans; 28 of these
      phlebograms were also correlated with magnetic resonance imaging scans of the
      thoracic veins. Eighteen of the 43 phlebograms were normal, and all had normal
      magnetic resonance imaging and duplex studies. Eleven subclavian veins were
      totally occluded on phlebography; all had duplex scans, and five were also
      scanned with magnetic resonance imaging. Duplex scans detected 6 of 11
      occlusions, whereas magnetic resonance imaging detected 4 of the 5 occlusions
      scanned. The five occlusions that were not detected by either magnetic resonance
      imaging or duplex scans were short segmental occlusions of the medial one third
      of the left subclavian vein. Of 14 nonocclusive thrombi seen on phlebography,
      duplex scans correctly identified 8. Magnetic resonance imaging was done on eight
      nonocclusive thrombi but identified only two. All abnormal findings on duplex
      scanning and magnetic resonance imaging were confirmed by phlebography. Short
      occlusions of the proximal portion of the left subclavian vein were often
      undetected by duplex scanning but occasionally seen with magnetic resonance
      imaging. Neither modality was sensitive to the presence of nonocclusive mural
      thrombi. Magnetic resonance imaging is highly reliable in ruling out the presence
      of a thrombotic process in the subclavian vein, but it may on occasion fail to
      detect the presence of subclavian thrombi. For this reason, in cases with
      suspected subclavian vein thrombosis magnetic resonance imaging cannot be used as
      the only diagnostic modality.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1999859
TI  - Popliteal artery aneurysms. Long-term follow-up of aneurysmal disease and results
      of surgical treatment.
AB  - The natural history of aneurysmal disease was analyzed in 50 patients who were
      treated for 71 popliteal aneurysms. No patients were lost to follow-up (mean, 5.0
      years). Initially, 25 popliteal aneurysms (25/71; 35%) were treated
      nonsurgically, and 46 (46/71; 65%) were treated surgically. Complications
      developed in 12 of the 21 asymptomatic popliteal aneurysms (57%) and in 2 of the
      4 symptomatic popliteal aneurysms (50%), which were treated nonsurgically. The
      probability of developing complications increased with time to 74% within 5
      years. When reconstruction of a popliteal aneurysm was performed, graft patency
      and foot salvage were 64% and 95% at 10 years, respectively. Particularly acute
      arterial thromboembolism was a severe presenting complication. Another important
      finding was the development of 23 arteriosclerotic aneurysms at other locations
      during follow-up in 16 patients (32%). The probability of developing these new
      aneurysms increased to 49% 10 years after repair of the initial popliteal
      aneurysm. The presence of multiple isolated aneurysms at the initial examination
      was the most significant risk factor limiting the survival of these patients.
      Consequently patients at risk could be identified early. This study confirms the
      limb-threatening potential of popliteal aneurysms when left untreated. Therefore
      prophylactic reconstructive surgery should be undertaken. Moreover, this study
      demonstrates that patients with a popliteal artery aneurysm have an increased
      risk of new aneurysm formation, both in the popliteal artery and at other
      locations. Therefore these patients should be followed and, in the event that new
      aneurysms develop, should be considered for elective reconstructive surgery to
      prevent limb-threatening or life-endangering complications.

PMID- 1999860
TI  - Occlusion of the brachial artery by thrombus dislodged from a traumatic aneurysm
      of the anterior humeral circumflex artery.
AB  - The successful treatment of a brachial artery occlusion caused by a chronic
      embolizing aneurysm of the anterior humeral circumflex artery is described. In
      the case of embolizing axillary artery aneurysms, the best therapy is resection
      of the aneurysm followed by distal thromboembolectomy and vascular reconstruction
      by a saphenous vein segment. Prosthetic material should be reserved as a second
      choice. In this particular case successful therapy consisted of ligation of the
      anterior humeral circumflex artery proximal and distal to the aneurysm, resection
      of the aneurysm, and transcubital thromboembolectomy.

PMID- 1999861
TI  - Interval gangrene of the lower extremity: a complication of vascular surgery.
AB  - Interval gangrene, segmental ischemic necrosis proximal to a functioning distal
      anastomosis, is a rare complication after successful peripheral vascular
      reconstruction. Previous reports have demonstrated the gravity of this event in
      that major limb amputation was required in all cases. Two cases are presented to
      emphasize the need for maintaining segmental collateral circulation after
      successful distal extremity bypass. Despite a satisfactory result after distal
      (inframalleolar) bypass of a popliteal aneurysm, one patient had progressive
      ischemic gangrene of the upper leg and eventually required amputation. The
      contralateral limb was successfully managed by distal ligation of the superficial
      femoral artery, which maintained collateral flow from the proximal superficial
      femoral artery to the knee and leg. The second patient required a microvascular
      free flap to replace tissue loss and provide vascular graft coverage after
      initial multiple bypass failures and a final successful remote reconstruction to
      the dorsal artery of the foot that excluded the popliteal-crural collateral
      network. Patients with inadequate collateral circulation or disruption of the
      profundus or geniculate collateral pathways may require revascularization of
      sequential vascular beds. Recognition of the potential for interval gangrene is
      essential since the likelihood of its occurrence will increase in proportion to
      the number of distal bypasses being performed for limb salvage. Although
      adjunctive procedures will not completely eliminate the possibility of interval
      gangrene, awareness of this phenomenon with attention to the segmental collateral
      circulation can decrease the incidence of its occurrence.

PMID- 1999862
TI  - Hemodynamic consequences of carotid-carotid bypass for innominate artery
      stenosis.
AB  - The carotid-carotid cervical bypass is one surgical option for symptomatic
      atherosclerotic lesions of the innominate artery. Controversy exists regarding
      the necessity of surgically excluding the innominate plaque from the cerebral
      circuit. A canine study was instituted to characterize the hemodynamic
      alterations that occur in the right common carotid artery proximal to the bypass
      graft, termed the critical segment. The direction of flow in the critical segment
      determines whether emboli originating in the innominate may be propelled
      cranially despite a patent bypass graft. Six mongrel dogs underwent placement of
      an autogenous arterial crossover graft as a carotid-carotid bypass. A stenosis of
      the innominate artery was quantitatively altered, and an electromagnetic
      flowmeter measured the magnitude and direction of flow in the critical segment at
      three levels of diameter reduction in the innominate artery. For low-grade
      stenoses, flow in the critical segment was always prograde. For high-grade
      stenoses, the flow was always reversed. Stenoses between 57% and 67% yielded flow
      values of 10 +/- 24 ml/min, and it was in this range that mean flow reversal was
      found to occur. Even when the mean flow was near zero in the critical segment,
      flow was not stagnant but oscillated in antegrade and retrograde directions
      throughout the cardiac cycle. These data indicate that a carotid-carotid bypass
      causes complete flow reversal in the critical segment when there is high-grade
      stenosis in the innominate artery. Theoretical analysis of the hemodynamic
      circuit indicated that arm exercise would augment retrograde flow in the critical
      segment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1999863
TI  - Skewflap versus long posterior flap in below-knee amputations: multicenter trial.
AB  - A multicenter trial of alternative techniques for below-knee amputation is
      described in which surgeons in 11 centers randomized 191 patients with end-stage
      occlusive vascular disease to two different methods of stump construction. The
      skewflap technique was performed in 98 and the long posterior flap was performed
      in 93. The two groups were well matched in respect to age, sex, smoking,
      diabetes, and indications for amputation. Early outcome was compared in terms of
      30-day mortality rate: skew 11 (11%) deaths versus long posterior flap 16 (17%);
      the state of the wound at 1 week (primary healing 60% in both groups); the need
      for surgical revision at the same level 7 (7%) versus 7 (8%), and revision to a
      higher level 10 (10%) versus 7 (8%). Follow-up information at 6 months was
      available from records or by mailed questionnaire in 188 (98%) at 6 months, 20
      died during that interval. It showed that a prosthetic limb was fitted to 64
      (84%) of skew flaps and 50 (77%) of long posterior flaps. Walking, alone or with
      support, was achieved in 59 (78%) and 46 (71%), respectively. None of these
      differences reached statistical significance. It is concluded that the skew flap
      is just as effective as the long posterior flap and is an excellent option for
      below-knee amputation.

PMID- 1999864
TI  - Hypoxia induces procoagulant activity in cultured human venous endothelium.
AB  - Although it normally presents a nonthrombogenic surface, endothelium is capable
      of procoagulant activity and suppression of native anticoagulant properties. We
      theorized that hypoxia could shift normal endothelium into a procoagulant state
      and tested this hypothesis in cultured human umbilical venous endothelial cells.
      Human umbilical venous endothelial cells were obtained from fresh umbilical
      cords. Passage two cells were placed in control (PO2 greater than 120 mm Hg) or
      hypoxic (PO2 less than 60 mm Hg) media and incubated in control or hypoxic
      environments for 24 hours. In additional experiments, cells were reoxygenated for
      4 or 48 hours after the initial hypoxic period. Cells were then assayed for
      procoagulant activity expressed as thromboplastin unit equivalents per 100,000
      cells based on a thromboplastin standard curve. Results are expressed as percent
      increase in thromboplastin unit equivalents/100,000 cells +/- standard error
      versus control. Statistical significance was assessed by paired t test with p
      less than 0.05 considered significant. More than 95% of cells in all experimental
      and control preparations were viable after completion of the protocols. No
      morphologic variation was noted among the control and hypoxic groups. For cells
      rendered hypoxic without reoxygenation, the mean increase in procoagulant
      activity for the group (n = 4) versus control was 77% +/- 13% (p = 0.01). In the
      hypoxia and 4-hour reoxygenation group (n = 4), the mean increase in procoagulant
      activity was 141% +/- 43% (p less than 0.05). In cells reoxygenated for 48 hours
      after hypoxia (n = 8), the mean increase in procoagulant activity was 198% +/-
      34% (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1999865
TI  - Diagnosis of popliteal artery entrapment syndrome: the role of duplex scanning.
AB  - The authors present a new diagnostic procedure to quickly and noninvasively
      diagnose the popliteal artery entrapment syndrome. A large personal experience on
      the surgical treatment of such a disease (29 cases in 22 patients) allowed us to
      focus on the optimal diagnostic procedure useful to detect this problem at an
      early stage. The technique is based on continuous-wave Doppler and duplex
      scanning studies done both in the resting state and during active contraction of
      the calf muscles. If compression of the popliteal artery occurs with contraction
      of the calf muscles, it will be detected by a decrease in flow. This finding will
      also direct the radiologist to obtain films when the maneuver is repeated. This
      makes it unlikely that the diagnosis will be missed. Since July 1988 a total of
      1212 patients were evaluated with continuous-wave Doppler for suspected chronic
      ischemia. From this group 41 patients were selected to be studied again with the
      combined continuous-wave Doppler and duplex scanning method for possible
      popliteal artery entrapment syndrome. Two cases were discovered and verified by
      dynamic angiography guided by continuous-wave Doppler and treated surgically.

PMID- 1999866
TI  - Limitations of electroencephalographic monitoring in the detection of cerebral
      ischemia accompanying carotid endarterectomy.
AB  - An analysis was undertaken of 458 consecutive carotid endarterectomies performed
      over 6 years with the patient under general anesthesia and with
      electroencephalographic monitoring. Seventy patients (15%) had
      electroencephalographic changes suggestive of ischemia with carotid clamping and
      had shunts placed. Ischemic encephalographic changes occurred in 26% of patients
      with an occluded contralateral carotid artery, 21% of patients with a prior
      stroke history, and 12% of patients with no stroke history and a patent
      contralateral carotid artery. Nineteen strokes (4.1%), nine transient deficits
      (2.0%), and one death (0.2%) occurred in the 458 endarterectomies in this
      experience. Ten of the 19 strokes and five of nine transient deficits were
      immediately apparent when patients awoke from anesthesia. Five of 10 patients
      with immediate strokes and all five patients with immediate transient deficits
      had no ischemic electroencephalographic changes during the procedure. Two other
      patients with immediate strokes initially had ischemic electroencephalographic
      changes after carotid clamping that reversed with increased blood pressure or
      shunting. Therefore 7 of 10 patients with immediate strokes and all 5 patients
      with immediate transient deficits had electroencephalographs unchanged from
      baseline at completion of the procedure, and thus deficits not manifest by
      operative electroencephalographic changes developed. Our data do not support the
      tenet that electroencephalographic monitoring will always predict neurologic
      deficits accompanying carotid endarterectomy.

PMID- 1999867
TI  - Low density lipoprotein uptake by an endothelial-smooth muscle cell bilayer.
AB  - To study the interaction of endothelial and smooth muscle cells, and the means by
      which such interaction may affect lipid permeability of the arterial wall, cell
      bilayers were established by use of a transwell culture system. After confluent
      growth of both cell types had been achieved, iodine 125 bound to low-density
      lipoprotein (10 ng protein/ml) was added to the media of the upper well. After a
      3-hour incubation period, the iodine 125-bound low-density lipoprotein content of
      the upper and lower media demonstrated an impedance to lipoprotein movement
      across the endothelial cell monolayer as compared to the bare porous
      polycarbonate filter of the transwell (p less than 10(-6)). The presence of
      smooth muscle cells in the bottom well significantly enhanced the permeability of
      the endothelial cell layer (p less than 10(-60). This effect remained unchanged
      over a 9-day time course. Membrane binding and cellular uptake of low-density
      lipoprotein by endothelial cells was not altered by smooth muscle cells,
      indicating that this change in permeability could not be easily attributed to
      changes in receptor-mediated transport or transcytosis. Membrane binding (p less
      than 0.02) and cellular uptake (p less than 10(-6)) of low-density lipoprotein by
      smooth muscle cells in the bilayer, when adjusted for counts available in the
      smooth muscle cell media, were both reduced in the early incubation period as
      compared to isolated smooth muscle cells. The disproportionate reduction in
      uptake as compared to binding would suggest that this was not entirely a receptor
      dependent process.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1999868
TI  - Suggested standards for reporting on arterial aneurysms. Subcommittee on
      Reporting Standards for Arterial Aneurysms, Ad Hoc Committee on Reporting
      Standards, Society for Vascular Surgery and North American Chapter, International
      Society for Cardiovascular Surgery.
AB  - The literature on arterial aneurysms is subject to potential misinterpretation
      because of inconsistencies in reporting standards. The joint councils of the
      Society for Vascular Surgery and the North American Chapter of the International
      Society for Cardiovascular Surgery appointed an ad hoc committee to address this
      issue. This communication, prepared in response to the need for standardized
      reporting, defines and classifies arterial aneurysms and recommends standards for
      describing the causes, manifestations, treatment, and outcome criteria that are
      important when publishing data on aneurysmal disease.

PMID- 1999869
TI  - The clinical role of the cerebral collateral circulation in carotid occlusion.

PMID- 1999871
TI  - Combined coronary artery bypass grafting and bilateral renal revascularization
      for unstable angina and impending renal failure.

PMID- 1999870
TI  - Use of the superficial femoral vein as a replacement for large veins.

PMID- 1999872
TI  - Medicine keeps pace as military moves from 'Garrison' to 'expeditionary'.

PMID- 1999874
TI  - From the Surgeon General, US Public Health Service.

PMID- 1999873
TI  - AIDS vaccines inch closer to useful existence.

PMID- 1999875
TI  - A piece of my mind. A lament for invalids.

PMID- 1999876
TI  - Bovine somatotropin.

PMID- 1999877
TI  - Cisplatin-induced urinary endothelin excretion.

PMID- 1999878
TI  - Preemployment drug screening and employment outcome.

PMID- 1999879
TI  - Mortality among workers at Oak Ridge National Laboratory. Evidence of radiation
      effects in follow-up through 1984.
AB  - White men hired at the Oak Ridge (Tenn) National Laboratory between 1943 and 1972
      were followed up for vital status through 1984 (N = 8318, 1524 deaths).
      Relatively low mortality compared with that in US white men was observed for most
      causes of death, but leukemia mortality was elevated in the total cohort (63%
      higher, 28 deaths) and in workers who had at some time been monitored for
      internal radionuclide contamination (123% higher, 16 deaths). Median cumulative
      dose of external penetrating radiation was 1.4 mSv; 638 workers had cumulative
      doses above 50 mSv (5 rem). After accounting for age, birth cohort, a measure of
      socioeconomic status, and active worker status, external radiation with a 20-year
      exposure lag was related to all causes of death (2.68% increase per 10 mSv)
      primarily due to an association with cancer mortality (4.94% per 10 mSv). Studies
      of this population through 1977 did not find radiation-cancer mortality
      associations, and identical analyses using the shorter follow-up showed that
      associations with radiation did not appear until after 1977. The radiation-cancer
      dose response is 10 times higher than estimates from the follow-up of survivors
      of the bombings of Hiroshima and Nagasaki, Japan, but similar to one previous
      occupational study. Dose-response estimates are subject to uncertainties due to
      potential problems, including measurement of radiation doses and cancer outcomes.
      Longer-term follow-up of this and other populations with good measurement of
      protracted low-level exposures will be critical to evaluating the
      generalizability of the results reported herein.

PMID- 1999880
TI  - Cancer in populations living near nuclear facilities. A survey of mortality
      nationwide and incidence in two states.
AB  - Reports from the United Kingdom have described increases in leukemia and lymphoma
      among young persons living near certain nuclear installations. Because of
      concerns raised by these reports, a mortality survey was conducted in populations
      living near nuclear facilities in the United States. All facilities began service
      before 1982. Over 900,000 cancer deaths occurred from 1950 through 1984 in 107
      counties with or near nuclear installations. Each study county was matched for
      comparison to three "control counties" in the same region. There were 1.8 million
      cancer deaths in the 292 control counties during the 35 years studied. Deaths due
      to leukemia or other cancers were not more frequent in the study counties than in
      the control counties. For childhood leukemia mortality, the relative risk
      comparing the study counties with their controls before plant start-up was 1.08,
      while after start-up it was 1.03. For leukemia mortality at all ages, the
      relative risks were 1.02 before start-up and 0.98 after. For counties in two
      states, cancer incidence data were also available. For one facility, the
      standardized registration ratio for childhood leukemia was increased
      significantly after start-up. However, the increase also antedated the operation
      of this facility. The study is limited by the correlational approach and the
      large size of the geographic areas (counties) used. It does not prove the absence
      of any effect. If, however, any excess cancer risk was present in US counties
      with nuclear facilities, it was too small to be detected with the methods
      employed.

PMID- 1999881
TI  - Motor vehicle crash injury patterns and the Virginia seat belt law.
AB  - Injuries to front seat occupants in tow-away crashes in the Charlottesville, Va,
      area were compared for 1 year before and 1 year after Virginia's seat belt use
      law took effect. Vehicle and occupant data were combined to examine crash and
      injury patterns. Reported seat belt use in crashes increased after the law, and
      there were substantial decreases in injuries. Front seat occupants were less
      likely to receive medical treatment following a crash in the postlaw period. The
      reduction in the number of injuries was greater for passengers in the right front
      seat than for drivers and for frontal crashes than for other types of crashes.
      The injury reduction effects occurred primarily through reductions in the number
      of head and face injuries, particularly those that occur from contact with
      windshields and instrument panels.

PMID- 1999882
TI  - Age-related characteristics of ambulatory blood pressure load and mean blood
      pressure in normotensive subjects.
AB  - Ambulatory blood pressure monitoring has become increasingly popular for
      diagnosing and treating hypertension. However, data from normotensive subjects
      are needed for interpretation of hypertensive readings. Ambulatory blood pressure
      was monitored in 126 normotensive subjects (age range, 20 to 84 years). Mean
      systolic and diastolic blood pressure and blood pressure loads (percentage of
      systolic readings greater than 140 mm Hg and diastolic readings greater than 90
      mm Hg) were obtained and interpreted. Mean awake systolic and diastolic pressures
      ranged from 125 +/- 10 to 137 +/- 17 mm Hg and 70 +/- 8 to 71 +/- 9 mm Hg,
      respectively. The systolic and diastolic trends of subjects' blood pressures
      taken during office visits and the 24-hour measurements were similar. Ranges for
      systolic and diastolic blood pressure loads from youngest to oldest ages were 9%
      +/- 14% to 25% +/- 20% and 3% +/- 7% to 4% +/- 7%, respectively. A comparison of
      blood pressure means from our sample that were taken during office visits and
      blood pressure means from a 2122-patient community survey demonstrated that our
      sample was reflective of an unselected population.

PMID- 1999883
TI  - Intrathecal baclofen for spasticity in cerebral palsy.
AB  - Seventeen patients with congenital spastic cerebral palsy and six patients with
      other forms of spasticity were injected intrathecally with doses of placebo or
      baclofen, 25 micrograms, 50 micrograms, or 100 micrograms, in a randomized,
      double-blind manner. Muscle tone in the upper and lower extremities was assessed
      by Ashworth scores both before the injections and every 2 hours afterward for 8
      hours. Function of the upper extremities was evaluated before the injections and
      4 hours afterward. Muscle tone in the lower extremities was significantly
      decreased within 2 hours after baclofen injection and remained lower than
      baseline 8 hours afterward. Upper extremity tone and function were not
      significantly affected by these single doses. Confusion and drowsiness occurred
      in two of the youngest children in the study after the 50-micrograms dose, but
      cleared within 2 hours. Our findings indicate that intrathecal baclofen reduces
      spasticity in children with cerebral palsy, as it does in adults with spasticity
      of spinal origin.

PMID- 1999884
TI  - A simple and inexpensive method of removal or replacement of gastrostomy tubes.
AB  - The safety of removal or replacement of gastrostomy tubes by simply cutting the
      tube and allowing the inner components to be eliminated intestinally was
      prospectively studied in 64 patients. In only one patient was the internal
      component lodged at the pylorus; it required endoscopic removal. Abdominal
      radiographs obtained in 57 patients confirmed complete elimination of internal
      percutaneous endoscopic gastrostomy components in 48 patients (84%) and
      identified these components in the colon in eight (14%). In two patients, the
      internal components were identified in the stool, and in one, radiographs were
      not obtained. Six patients who did not have abdominal radiographs had no problems
      during a mean follow-up period of 153.3 +/- 37.2 days. This simple method is
      safe, inexpensive, can be offered to the large majority of patients with
      percutaneous endoscopic gastrostomy tubes, and avoids the need for endoscopic
      removal.

PMID- 1999886
TI  - There's no free lunch. The benefits and risks of technologies.

PMID- 1999887
TI  - Risk of cancer mortality in populations living near nuclear facilities.

PMID- 1999885
TI  - Biotechnology and the American agricultural industry. Council on Scientific
      Affairs, American Medical Association.
AB  - To meet the needs of a rapidly growing population and minimize the toxic
      influences of traditional farming practices on the environment, the American
      agricultural industry has applied molecular technology to the development of food
      crops and livestock. By placing genes specific for highly desirable phenotypes
      into the DNA of plants, animals, and bacteria, farmers have increased crop and
      livestock survival, enhanced the nutritional quality of foods, increased industry
      productivity, and reduced the need for toxic pesticides and herbicides. However,
      introduction of genetically modified foods into the marketplace has raised a
      spectrum of public health issues. Physicians, as the most proximal scientific
      resource for most individuals, are uniquely positioned to address patient
      concerns regarding the safety of genetically altered foods. This report provides
      an overview of the inherent risks and benefits of "agrogenetics" and offers a
      series of recommendations designed to promote the education of the medical
      community and dispel public misconception regarding genetic manipulation.

PMID- 1999888
TI  - Clinical decision making: from theory to practice. The individual vs society. Is
      there a conflict?

PMID- 1999889
TI  - Allergy to sulfa drugs with postcoital urticaria.

PMID- 1999890
TI  - Power lines and cancer risk.

PMID- 1999891
TI  - Desert Storm: medical airlift was ready.

PMID- 1999892
TI  - Schizophrenia therapy controversy continues.

PMID- 1999894
TI  - From the Centers for Disease Control. Acute allergic reactions associated with
      reprocessed hemodialyzers--United States, 1989-1990.

PMID- 1999893
TI  - From the Agency for Health Care Policy and Research.

PMID- 1999895
TI  - HIV testing of pregnant women and newborns.

PMID- 1999896
TI  - Medical law, medical ethics.

PMID- 1999897
TI  - Risk factors for measles in a vaccinated population.

PMID- 1999898
TI  - Paresthesia and numbness due to drugs: the special case of the blind.

PMID- 1999900
TI  - The FDA and drug marketing expenditures.

PMID- 1999899
TI  - Crack smiles.

PMID- 1999901
TI  - Sandoz and the monitoring of patients receiving clozapine.

PMID- 1999902
TI  - The prescription and proscription of chorionic gonadotropin.

PMID- 1999903
TI  - Blood contacts during surgical procedures.
AB  - Operating room personnel are at risk for infection with blood-borne pathogens
      through blood contact. To describe the nature and frequency of blood contact and
      its risk factors, trained observers monitored a sample of operations performed by
      six surgical services at Grady Memorial Hospital, Atlanta, Ga, for 6 months. In
      62 (30.1%) of 206 operations, at least one blood contact was observed. Of 1828
      operating room person-procedures observed, 96 (5.3%) had 147 blood contacts (133
      skin contacts [90%], 10 percutaneous injuries [7%], and four eye splashes [3%]).
      The mean number of blood contacts per 100 person-procedures was highest for
      surgeons (18.6). The frequency of percutaneous injury was similar among surgeons
      and scrub staff (mean, 1.2 per 100 worker-procedures for each group). Risk
      factors for surgeons' blood contacts were (1) performing a trauma, burn, or
      orthopedic emergency procedure (odds ratio [OR], 4.1; 95% confidence interval
      [CI], 2.0 to 8.7); (2) patient blood loss exceeding 250mL (OR, 2.1; 95% CI, 1.2
      to 3.7); and (3) being in the operating room longer than 1 hour (OR, 3.3; 95% CI,
      1.6 to 7.1). Of 110 blood contacts among surgeons, 81 (74%) were potentially
      preventable by additional barrier precautions, such as face shields and fluid
      resistant gowns. Twenty-one (84%) of 25 blood contacts among surgeons in
      procedures in which all three risk factors were present were potentially
      preventable by additional barriers. Of 29 blood contacts among anesthesia and
      circulating personnel, 20 (69%) would have been prevented by glove use. For
      surgical procedures in which operating room personnel are at increased risk of
      blood contact, reevaluation of surgical technique, use of appropriate barrier
      precautions, and development of puncture-resistant glove materials are indicated.

PMID- 1999904
TI  - The origin of the full-time faculty system. Implications for clinical research.
AB  - Clinical research has long been viewed as a fragile pursuit requiring special
      nurturing. The full-time clinical faculty system was introduced in the early 20th
      century to provide a milieu that would foster clinical investigation. This
      article, based on extensive archival research, will show that the main goal of
      the architects of the full-time system was to stimulate research by removing the
      incentive for medical professors to devote their main energy to practice. The
      plan was developed by preclinical scientists at The Johns Hopkins Medical School
      (Baltimore, Md) and was inaugurated there in 1913 with the financial assistance
      of the Rockefeller General Education Board. As other medical schools adopted
      traditional academic criteria for appointment and advancement, there were
      additional incentives for faculty members to undertake research. In the 1920s,
      the General Education Board yielded to pressure to liberalize its definition of
      full time and began to support medical schools that implemented what came to be
      known as the "geographic full-time plan." Increased government support and other
      factors encouraged the expansion of full-time plans and led to an impressive
      increase in the output of research. Today, growing pressure on full-time clinical
      faculty members to generate income from practice for themselves and their
      institutions threatens the future of clinical research in this country.

PMID- 1999905
TI  - Successful treatment of cat-scratch disease with ciprofloxacin.
AB  - Cat-scratch disease is usually a benign, self-limited disease. Infection may be
      asymptomatic but is commonly associated with painful regional lymphadenitis.
      Occasionally, disease may result in systemic symptoms and dissemination. Five
      adult patients, aged 24 to 57 years, were diagnosed as having cat-scratch
      disease, based on a positive history of cat scratches followed by typical
      symptoms including painful regional lymphadenitis, malaise, and positive cat
      scratch skin tests. Diagnostic evaluations revealed no other cause for the
      lymphadenitis. Three patients had not received prior treatment with antibiotics,
      and two patients had failed to improve on other antibiotics. All five were
      treated with oral ciprofloxacin, 500 mg by mouth, twice daily. All patients had
      dramatic improvement in symptoms within a few days and none has relapsed during
      follow-up. This is the first report of successful treatment of cat-scratch
      disease with ciprofloxacin, which appears to be an effective therapy for cat
      scratch disease in adults.

PMID- 1999906
TI  - Antihypertensive therapy. To stop or not to stop?
AB  - The benefits of continuous antihypertensive therapy have been extensively
      documented. However, lack of compliance with the prescribed regimen, excessive
      cost, and troublesome adverse effects of some antihypertensive agents led to the
      consideration of intermittent therapy or even complete discontinuation of therapy
      as an effective alternative to lifelong medication. Prospective studies dealing
      with this subject reported inconsistent results. Nevertheless, they allowed us to
      identify selection criteria of candidates for step-down or discontinuation of
      antihypertensive therapy. Such candidates include patients with mild essential
      hypertension who have one or more of the following characteristics: young age,
      normal body weight, low salt intake, no alcohol consumption, low pretreatment
      blood pressure, successful therapy with one drug only, and no or only minimal
      signs of target organ damage. Stopping antihypertensive therapy without
      subsequent rise in arterial pressure was shown to be possible in a subset of
      patients with mild essential hypertension for a period of months to years. This
      approach appears to be safe, provided that blood pressure is monitored
      frequently, and may improve compliance, save treatment costs, and reduce adverse
      effects of certain drugs, although its long-term consequences for morbidity and
      mortality remain to be determined.

PMID- 1999907
TI  - Surgery and AIDS. Reducing the risk.

PMID- 1999908
TI  - From the Office of the General Counsel. Denying treatment to the noncompliant
      patient.

PMID- 1999909
TI  - Anesthesia for patients with preeclampsia.

PMID- 1999910
TI  - Phosphatidylcholine prevents postoperative peritoneal adhesions: an experimental
      study in the rat.
AB  - Phosphatidylcholine (PC) is the main constituent of the surface-active material
      coating peritoneal mesothelium. It may prevent postoperative adhesion formation
      through production of a lubricant film on mesothelial defects. We therefore
      examined the effect of its soluble form on surgically induced intraabdominal
      adhesions in rats. The adhesions were induced at laparotomy by any of four
      different operative models. PC was administered intraperitoneally (20 mg/rat) or
      intravenously (20 mg/rat or 50 mg/rat) at the end of the operation and on the
      second and third postoperative day. It was found that the degree of postoperative
      adhesion formation was significantly reduced by the intraperitoneal injection of
      PC in all 4 models. In contrast, no effect was achieved by the intravenous
      injection of PC, not even at a very high dose level. Our results suggest that
      soluble PC administered intraperitoneally might be a potent adjunct in
      postoperative adhesion prevention.

PMID- 1999911
TI  - Liver metastases induced by implantation of VX2 cancer into the gastrointestine.
AB  - An experimental model with a high frequency of spontaneous liver metastases was
      induced by implantation of VX2 cancer cells into the gastrointestinal walls of 36
      rabbits, and the developmental process of primary cancer lesions and metastases
      was examined histologically. Gastric and colonic cancer lesions showed similar
      growth patterns in both primary and metastatic lesions: the average diameter of
      primary lesions enlarged from 0.7-0.8 cm on Day 7 to 2.4-2.8 cm on Day 28. The
      frequency and average diameter of liver metastases were 25% and microscopically
      certificated levels on Day 14, 25% and 3 mm on Day 21, and 50% and 8 mm on Day 28
      in the gastric wall-implantation group. They were, respectively, 20% and
      microscopically recognized levels on Day 14, 40% and 2 mm on Day 21, and 80% and
      9 mm on Day 28 in the colonic wall-implantation group. Thus, the frequency and
      diameter of the metastases increased in parallel with the primary cancer growth.
      Liver metastases occurred only in animals with vascular invasion in primary
      lesions, though none of the animals with the invasion always showed the
      metastases. These results suggest that vascular invasion of cancer cells in the
      primary lesions may be a premise of liver metastases, and that this experimental
      model may be utilized as a useful tool for studying many aspects of the
      pathogenesis and/or therapy of the spontaneous liver metastases in
      gastrointestinal cancer.

PMID- 1999912
TI  - Contribution of portal systemic shunt to Kupffer cell dysfunction in obstructive
      jaundice.
AB  - Previous animal models of biliary tract obstruction have shown that hepatic
      phagocytic activity is impaired secondary to Kupffer cell dysfunction. Biliary
      tract obstruction leads to portal hypertension and an associated portal systemic
      shunt. Forty-eight Sprague-Dawley rats were studied to determine the contribution
      of portal systemic shunt to Kupffer cell dysfunction after 21 days of obstructive
      jaundice or sham operation. Liver uptake of radiolabeled Escherichia coli
      decreased from 76.1 +/- 1.4% (sham) to 63.1 +/- 6.1% in the common duct ligation
      (CDL) rats (P less than 0.05); lung uptake increased from 4.0 +/- 0.6% (sham) to
      20.2 +/- 4.5 (CDL) (P less than 0.05). Portal systemic shunt, determined using
      radioactive microspheres, increased from 2.0 +/- 1.0% (sham) to 46.6 +/- 13.1%
      (CDL), P less than 0.05. Although a significant portal systemic shunt does exist
      in this 21-day model of obstructive jaundice, it does not appear to be the only
      mechanism underlying Kupffer cell dysfunction.

PMID- 1999913
TI  - Increased hyaluronan flux from skin following burn injury.
AB  - Hyaluronan (formerly hyaluronic acid) is an important constituent of the
      interstitial matrix in skin. Following major burn injury in animal models, plasma
      hyaluronan can increase to levels 10-fold greater than normal. The present
      experiments were designed to determine whether this is a result of the increased
      lymph flow (QL) accompanying the injury or of an increased release of hyaluronan
      from the burned skin and subcutaneous tissue. The lateral saphenous vein and a
      prenodal lymphatic were cannulated in the hindpaw of five anesthetized canines.
      Hindpaw venous pressure was elevated until the total protein concentration in
      lymph declined to steady-state levels, and QL and hyaluronan flux (QL X
      [hyaluronan]) was measured. A minor burn was inflicted by immersion of the paw
      into 100 degrees C water for five sec, and measurements were repeated at regular
      intervals for a minimum of 4 hr. Burn injury resulted in significant and
      persistent increases in QL (154 +/- 61 microliters/min versus 562 +/- 105
      microliters/min 4 hr postburn) and lymph total protein concentration (1.34 +/-
      0.04 g/dl versus 4.08 +/- 0.18 g/dl 4 hr postburn), while lymph hyaluronan
      concentration fell (3.01 +/- 0.20 micrograms/ml versus 2.1 +/- 0.16 micrograms/ml
      4 hr postburn). The resultant increase in hyaluronan flux (0.42 +/- 0.13
      microgram/min versus 1.17 +/- 0.22 microgram/min 4 hr postburn) appears to be a
      function of lymph flow rather than burn-induced release of skin hyaluronan.
      Hence, the increased plasma concentration of hyaluronan following major burns is
      likely a consequence of increased lymph flow from the site of injury.

PMID- 1999914
TI  - Stenosis following laser thermal angioplasty--a blinded controlled randomized
      study between aspirin against Probucol.
AB  - Long-term patency of vascular angioplasties is limited by stenosis from
      neointimal hyperplasia or progressive arteriosclerosis. This study evaluated the
      hypothesis that ASA (an antiprostaglandin) or Probucol (an antioxidant) may be
      useful in preventing stenosis following laser thermal angioplasty. Aortoiliac
      arteriosclerosis was induced in 17 female New Zealand white rabbits with a
      combination of endothelial denudation (4 Fr. Fogarty balloon catheters) and 2%
      cholesterol-supplemented diet for 6 weeks. All rabbits then underwent
      arteriography and were immediately randomized to one of three groups: Group I (n
      = 6), control, laser but no adjunctive therapy; Group II (n = 5), laser and ASA
      10 mg/kg/day; Group III (n = 6), laser and 1% Probucol diet. Retrograde laser
      thermal angioplasty was performed with a 1-mm coronary Laserprobe. Six watts of
      argon laser energy was delivered for a single 5-sec pulse using a continuous
      motion from the right common iliac artery to the aorta. Pre- and postlaser
      arteriography was performed in all groups. Rabbits were sacrificed 1 month
      following laser angioplasty, and aortoiliac sections were taken after in situ
      perfusion fixation with paraformaldehyde and 0.05% glutaraldehyde. Serial 5-mm
      segments, proximal to the aortic bifurcation and distally from the same, were
      taken, stained, and evaluated by quantitative morphometry. From each segment,
      lesion area and lesion area/internal elastic laminae area were evaluated and
      compared. Serum cholesterol increased from 60.8 +/- 19.5 to 1494.7 +/- 12.7 mg%
      following institution of the cholesterol diet (P less than 0.05).
      Arteriosclerotic lesions were observed in all rabbits and maximally located
      around the common iliac artery.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1999915
TI  - Marked increase of plasma hyaluronan after major thermal injury and infusion
      therapy.
AB  - Hyaluronan (HYA) is an important structural element in skin and is presumably
      participating in regulation of the interstitial fluid volume. HYA is transported
      via the lymphatics from the tissues to the blood, where its concentration is
      normally very low. Fluid flux through the interstitium is markedly increased
      after thermal injury. The present study was performed to determine whether major
      thermal injury would affect plasma levels of HYA. In halothane-anesthetized sheep
      subjected to 40% BSA full-thickness scald burns, plasma HYA concentration
      increased from 116 +/- 19 (mean +/- SEM) to 172 +/- 18 ng/ml within 1 hr after
      injury (P less than 0.05). After 3 hr of fluid therapy plasma HYA concentration
      was further elevated to 10 times baseline (1417 +/- 322 ng/ml) (P less than
      0.01). To clarify whether this rise represented an increased "washout" of
      interstitial HYA, attributable either to the burn injury or the subsequent fluid
      therapy, awake sheep were subjected to overhydration. Following a 3-hr infusion
      of lactated Ringer's 2.5 liter/hr, plasma HYA concentration increased to 2-3
      times baseline. Lung lymph flow and its concentration of HYA increased, leading
      to an increase in the lymphatic flux of HYA to 10-20 times baseline. In
      peripheral lymph HYA flux increased 2-3 times baseline. Infusion of lactated
      Ringer's markedly increased lymphatic removal of HYA. However, plasma
      concentrations of HYA were 3 times higher after thermal injury than following
      fluid challenge alone, suggesting that thermal injury per se may also increase
      input of HYA into the systemic circulation.

PMID- 1999916
TI  - Thermal skin injury: effect of fluid therapy on the transcapillary colloid
      osmotic gradient.
AB  - The effects of fluid therapy on interstitial colloid osmotic and hydrostatic
      pressures in thermally injured skin were investigated in anesthetized rats
      subjected to full-thickness scald burns to 40% of the body surface area and
      resuscitation for 3 hr by either lactated Ringer's or plasma. Interstitial fluid
      hydrostatic pressure (Pif) was reduced from -2 mm Hg to -20 to -40 mm Hg after
      injury, which will profoundly increase transcapillary filtration. Following the
      onset of fluid therapy, Pif increased to slightly positive values. In control,
      colloid osmotic pressure in plasma (COPp) was 20.6 +/- 0.4 mm Hg and in
      interstitial fluid (COPif) 13.7 +/- 0.3 mm Hg (means +/- SEM). The transcapillary
      oncotic pressure gradient (COPgrad = COPp-COPif) was 6.9 +/- 0.4 mm Hg. Following
      nonresuscitated thermal injury, COPp declined to 18-19 mm Hg (P less than 0.05)
      and COPif was reduced to 10.4 +/- 0.5 mm Hg (P less than 0.05). Fluid therapy by
      lactated Ringer's markedly reduced COPp (12.3 +/- 0.3 mm Hg; P less than 0.05),
      and COPgrad was almost abolished (2.6 +/- 0.7 mm Hg; P less than 0.05). In
      contrast, plasma infusion maintained COPp, whereas COPgrad increased
      significantly (11.1 +/- 1.2 mm Hg; P less than 0.05). Noncolloid saline solutions
      have been preferred for the initial fluid therapy for burns. The present study
      provides evidence that this will reduce both COPp and COPgrad, a situation in
      which edema formation will be favored.

PMID- 1999917
TI  - Construction of peritoneal venous valves: an experimental study in rats and
      piglets.
AB  - In the search for new techniques to improve venous valve insufficiency, a
      peritoneal patch with a mesothelial layer on either side was employed in the
      venous circulation to construct a venous valve de novo. This material was used
      because of the resemblance in fibrinolytic activity of mesothelial cells to
      endothelium. The behavior of double-sided flaps of peritoneum was first studied
      on only one side in the caval vein wall of 10 rats. All veins remained open, and
      smooth incorporation of the patch into the vein wall was observed. It was
      therefore decided to use the same material for construction of a cusp blade in
      the venous circulation. This venous reconstruction was microsurgically performed
      in 21 rats and 4 piglets. In our hands, intramuscular anesthesia proved superior
      to intraperitoneal analgesia in rats. For the piglets mechanical ventilation and
      general anesthesia were used. In 9 of 21 rats a fair or good result was observed,
      although it did not seem possible to create a fully competent valve with only one
      cusp blade in the 1.5-mm-diam caval veins. The same fact evolved from the study
      using four 7-mm-diam piglet veins. All peritoneal flaps in the venous circulation
      demonstrated rebuilding of their structure, perhaps induced by the relatively
      exaggerated central venous flow. To our knowledge, this technique has never been
      used before. It seems to offer many advantages in the venous circulation, where
      hardly any thrombogenic surface is tolerated in contrast to the arterial
      circulation. Application in humans is yet premature, but future research may
      resolve several problems that occurred in this study.

PMID- 1999919
TI  - Nursing homes: reducing the impact of institutionalization.

PMID- 1999918
TI  - A comparison of hypertonic to isotonic fluid in the resuscitation of brain injury
      and hemorrhagic shock.
AB  - We studied the early and late effects of hypertonic resuscitation (HR) on the
      injured brain using a porcine model of hemorrhagic shock and focal cryogenic
      brain injury. After shock, swine were randomly assigned to receive a bolus (4
      cc/kg) of either Ringers lactate (RL) or 7.5% hypertonic saline in 6% Dextran 70,
      followed by either RL or hypertonic sodium lactate to restore mean arterial
      pressure to baseline. All animals were studied for 24 hr after the start of
      resuscitation. Bolus HR improved cerebral blood flow (CBF) with a lower
      intracranial pressure (ICP) than RL. Continued hypertonic resuscitation prolonged
      the period of improved CBF and low ICP. At 24 hr CBF had deteriorated in the
      region of injury in all study groups and in the uninjured hemisphere in swine
      receiving RL. These data suggest that rapid resuscitation without increasing ICP
      for up to 6 hr as seen with hypertonic fluid could conceivably allow adequate
      time for surgical evacuation of mass lesions and effectively prevent secondary
      brain injury. This work underscores the importance of prolonged periods of study
      when evaluating brain resuscitation from traumatic shock.

PMID- 1999920
TI  - Immediate reconstruction of maxillofacial gunshot injuries.

PMID- 1999921
TI  - An elderly woman with weight loss.

PMID- 1999922
TI  - A case of noncardiogenic pulmonary edema.

PMID- 1999923
TI  - Unsteady gait and seventh nerve palsy in an elderly woman.

PMID- 1999924
TI  - The reduction of black infant mortality: an 18-month evaluation of three
      Tennessee Black Health Care Task Force demonstration projects.

PMID- 1999925
TI  - Medicine--a business or profession?

PMID- 1999926
TI  - Old dog and old tricks.

PMID- 1999928
TI  - Alas, the poor cochlea.

PMID- 1999927
TI  - The living will.

PMID- 1999929
TI  - The customer is always right.

PMID- 1999930
TI  - Environmental noise and fetal hearing.

PMID- 1999931
TI  - Pioneers on the road to thoracic surgery.

PMID- 1999932
TI  - The effect of muscle-sparing versus standard posterolateral thoracotomy on
      pulmonary function, muscle strength, and postoperative pain.
AB  - Increased interest in alternative approaches to thoracotomy has developed because
      of the considerable morbidity associated with the standard posterolateral
      technique. We conducted a prospective, randomized, blinded study of 50
      consecutive patients to compare postoperative pain, pulmonary function, shoulder
      strength, and range of shoulder motion between the standard posterolateral and
      the muscle sparing thoracotomy techniques. Pulmonary function (forced expiratory
      volume in 1 second and forced vital capacity), shoulder strength, and range of
      motion were measured preoperatively and at 1 week and 1 month postoperatively.
      Pain was quantitated by postoperative narcotic requirements, the visual analogue
      scale, and the McGill pain questionnaire. Morbidity, mortality, and hospital stay
      were compared between the standard posterolateral and muscle-sparing techniques.
      There were no differences in postoperative pulmonary function, shoulder range of
      motion, extent of lung resection, surgical approach time, mortality, or hospital
      stay. There was significantly less postoperative pain in the muscle-sparing
      group. The narcotic requirement was less in the first 24 hours (p = 0.0169), and
      visual analogue scale scores were significantly lower (p less than 0.05)
      throughout the first postoperative week. Shoulder girdle strength was decreased
      at 1 week in the standard incision group whereas the strength was preserved with
      the muscle-sparing approach. Muscle strength had returned to preoperative levels
      by 1 month in both groups. Morbidity was identical in the two groups with the
      exception of postoperative seromas. The prevalence of seroma was 23% in the
      muscle-sparing group and 0% in the standard incision group (p = 0.0125). We have
      demonstrated that the muscle-sparing incision may be a reasonable alternative to
      the standard posterolateral approach.

PMID- 1999933
TI  - The surgical treatment of atrial fibrillation. I. Summary of the current concepts
      of the mechanisms of atrial flutter and atrial fibrillation.
AB  - Atrial fibrillation is a common arrhythmia that is frequently resistant to
      medical therapy and has no satisfactory surgical therapy. The development of an
      effective surgical procedure to treat atrial fibrillation has been hampered by
      the paucity of clinically relevant information on the basic mechanisms
      responsible for the arrhythmia. This paper summarizes the current concepts of the
      electrophysiologic abnormalities in atrial flutter and fibrillation.

PMID- 1999934
TI  - The surgical treatment of atrial fibrillation. II. Intraoperative
      electrophysiologic mapping and description of the electrophysiologic basis of
      atrial flutter and atrial fibrillation.
AB  - Computerized mapping of atrial fibrillation was performed in animals and man. To
      study atrial fibrillation in a systematic manner, we developed a clinically
      relevant experimental model of atrial fibrillation. Chronic mitral regurgitation
      was created surgically in 25 dogs without opening the pericardium. After several
      months of chronic mitral regurgitation, the atria became enlarged and sustained
      atrial fibrillation could be induced by standard programmed electrical
      stimulation techniques. Computerized isochronous activation maps of the atria
      were recorded during atrial fibrillation from 208 bipolar electrodes
      simultaneously. In a parallel study, human atrial fibrillation was mapped with a
      separate 160-channel intraoperative mapping system in patients with paroxysmal
      atrial fibrillation who were undergoing surgical correction of the Wolff
      Parkinson-White syndrome. The canine activation sequence maps demonstrated a
      spectrum of rhythm abnormalities ranging from simple atrial flutter to complex
      atrial fibrillation. They also showed that macroreentrant circuits within the
      atrial myocardium were responsible for the entire spectrum of arrhythmias. Atrial
      reentry was also documented during human atrial fibrillation. All patients had
      nonuniform conduction around regions of bidirectional block in both atria
      resulting in multiple discrete wave fronts. In addition, six patients had a
      single reentrant circuit in the right atrium in which bidirectional block of the
      activation wave front occurred along the sulcus terminals between the venae
      cavae. The left atrium in all patients demonstrated multiple wave fronts and
      conduction block, but left atrial reentry could not be detected. Both the
      experimental study and the clinical study demonstrated that multiple wave fronts,
      nonuniform conduction, bidirectional block, and large (macroreentrant) reentrant
      circuits occur during atrial fibrillation. The presence of macroreentrant
      circuits and the absence of either microreentrant circuits or evidence of atrial
      automaticity suggests that atrial fibrillation should be amenable to surgical
      ablation.

PMID- 1999935
TI  - Comparison of two levels of anticoagulant therapy in patients with substitute
      heart valves.
AB  - After cardiac valve replacement patients were blindly randomized into two groups,
      both receiving aspirin (330 mg) and dipyridamole (75 mg) twice daily and the oral
      anticoagulant acenocoumarol (Sintrom). An international normalized ratio of 2.0
      to 2.99 was assigned to group A and 3.0 to 4.5 to group B; both groups were
      subsequently analyzed for thromboembolic and hemorrhagic complications. Final
      evaluation included 51 and 48 patients, respectively. The follow-up was 626
      months for group A (12.3 months/patient) and 486 months for group B (10.1
      months/patient). The frequency of thromboembolism was equal in both groups: one
      transient ischemic attack in group A (a rate of 1.92/100 patient-years) and two
      transient ischemic attacks in group B (a rate of 4.94/100 patient-years). There
      was, however, a statistical difference in bleeding complications between the two
      groups (p less than 0.02). Two patients bled in group A, a rate of 3.9% (3.8/100
      patient-years), which represents an incidence of one episode each 25.6 years of
      treatment; 10 patients bled in group B, a rate of 20.8% (24.7/100 patient-years)
      representing an incidence of one episode each 4 years of treatment. We conclude
      that an international normalized ratio of 2 to 3 is safer than a ratio of 3 to
      4.5 and confers good protection from thromboembolism when oral anticoagulant
      therapy is used conjointly with platelet function-inhibiting drugs in patients
      with mechanical substitute heart valves.

PMID- 1999936
TI  - Analysis and predictors of pulmonary vascular resistance after cardiac
      transplantation.
AB  - Elevated pulmonary vascular resistance is a known risk factor for early death
      from acute right ventricular failure after orthotopic cardiac transplantation.
      Patients in whom the elevated pulmonary vascular resistance is due primarily to
      increased left atrial pressure ("reactive") frequently have normalization of
      resistance after transplantation, but few studies have detailed the time course
      and magnitude of these changes. To analyze the response of pulmonary vascular
      resistance to cardiac transplantation, we analyzed data from 4353 right heart
      catheterizations on all 182 patients undergoing cardiac transplantation between
      1981 and Jan. 1, 1990. Before transplantation 18% of patients had a pulmonary
      vascular resistance greater than 4 WU, 16% had a pulmonary artery systolic
      pressure greater than 60 mm Hg, and 16% had a transpulmonary gradient greater
      than 14 mm Hg. In the overall group of patients, pulmonary vascular resistance
      (mean value 2.63 WU), transpulmonary gradient (mean value 9.9 mm Hg), and
      pulmonary artery systolic pressure (mean value 48.0 mm Hg) were normalized within
      1 week of cardiac transplantation. In patients with a high preoperative pulmonary
      vascular resistance (greater than or equal to 4 WU), the resistance fell promptly
      within 1 week of transplantation but continued to be slightly elevated throughout
      the period of follow-up. By multiple regression analysis, pulmonary vascular
      resistance at 1 week and 1 year after transplantation was significantly
      correlated with the pretransplantation resistance. Pulmonary vascular resistance
      anytime after transplantation was related to preoperative resistance, body
      surface area, and pulmonary artery diastolic pressure. Inferences: (1) As a
      group, cardiac transplant recipients have a normal pulmonary vascular resistance,
      transpulmonary gradient, and pulmonary artery systolic pressure within 1 week
      after transplantation with little change thereafter for at least several years.
      (2) Patients with reversible elevation of pulmonary vascular resistance before
      cardiac transplantation typically have a reactive and a fixed component. Cardiac
      transplantation relieves the reactive but not the fixed component. As a result,
      pulmonary vascular resistance early (within 1 week) and late after
      transplantation will have fallen but not completely normalized.

PMID- 1999937
TI  - The mechanism of heart failure caused by cardiac allograft rejection.
AB  - Rejection of the cardiac allograft is often associated with reversible myocardial
      failure, the mechanism of which is not understood. We have examined this
      phenomenon in a small animal model that provides the opportunity for
      multimodality study of the rejection process. Heterotopic cardiac transplantation
      was performed in the Lewis rat with Lewis X Brown-Norway (allografts) or Lewis
      (isografts) donors. Without immunosuppression, allografts are completely rejected
      in 6 to 8 days. At 3 days cardiac grafts were explanted and mounted on a modified
      Langendorff apparatus for functional measurements or submitted for pathologic
      examination and biochemical determination of high-energy phosphates. Three-day
      isografts (n = 9) had minimal histologic changes. Pathologic examination of 3-day
      allografts (n = 13) showed lymphocytic infiltrate and myocyte necrosis,
      histologic features for which antirejection treatment is usually given
      clinically. For grafts subjected to functional studies (n = 11), heart rate,
      cardiac output, coronary flow, and stroke work were determined at baseline and in
      response to isoproterenol (3 x 10(-8) mol/ml). Three-day allografts (n = 6) and
      isografts (n = 5) had similar baseline function. The chronotropic response to
      isoproterenol was similar in allografts and isografts, but allografts had
      diminished cardiac output and stroke work after isoproterenol. Adenosine
      triphosphate levels were normal (41.9 nmol/mg) in 3-day allografts (n = 4). We
      have evaluated functional, biochemical, and pathologic changes associated with
      myocardial dysfunction during heterotopic cardiac transplant rejection in a small
      animal. This model reproducibly demonstrates diminished contractile reserve in 3
      day allografts with normal baseline function and high-energy stores but
      histologically significant rejection.

PMID- 1999938
TI  - Emergency cardiopulmonary bypass support in patients with cardiac arrest.
AB  - Emergency percutaneous cardiopulmonary bypass support was instituted in 11
      patients in cardiac arrest refractory to conventional resuscitation measures.
      Emergency percutaneous cardiopulmonary bypass support was used in five patients
      in whom cardiac arrest occurred as a result of a complication in the cardiac
      catheterization laboratory (group 1) and in six other patients in cardiac arrest
      (group II). A 21F cannula and a 17F cannula were percutaneously inserted into the
      femoral vein and artery. Flow rates of 3 to 5 L/min were achieved with
      restoration of mean arterial pressure to 70 mm Hg (range 50 to 75). The status of
      all 11 patients was improved initially both clinically and hemodynamically with
      percutaneous cardiopulmonary bypass. Of the group II patients, three had anatomy
      unsuitable for percutaneous transluminal coronary angioplasty or coronary bypass
      grafting, could not be weaned from cardiopulmonary support, and died; three of
      these patients had coronary artery bypass grafting and two survived. All five
      group I patients underwent successful coronary bypass grafting and survived. Of
      the seven patients with anatomically correctable disease, all seven were
      discharged from the hospital. With conventional management nearly all seven of
      these patients would have died. Nine of 11 patients underwent a cardiac operation
      and seven of the nine survived. The operative mortality rate was 22% and the
      overall survival rate was 64%. At follow-up (mean 7 months), all seven patients
      are alive and six have resumed a normal and active life-style. In conclusion,
      emergency percutaneous cardiopulmonary bypass support is a powerful resuscitative
      tool that may stabilize the condition of patients in cardiogenic shock and
      cardiac arrest to allow for definitive intervention.

PMID- 1999939
TI  - Studies of controlled reperfusion after ischemia. XXIII. Deleterious effects of
      simulated thrombolysis preceding simulated coronary artery bypass grafting with
      controlled blood cardioplegic reperfusion.
AB  - This study tests whether simulated thrombolysis before controlled reperfusion
      (i.e., simulated coronary artery bypass) causes reperfusion injury that obviates
      the benefits of subsequent controlled reperfusion and results in unnecessary
      ventricular arrhythmias. Fifteen dogs underwent acute occlusion of the left
      anterior descending coronary artery. In 10 dogs we simulated thrombolysis after 1
      hour of ischemia (delivering 10% to 15% of control flow at 5 ml/min), followed 1
      hour later by either normal blood reperfusion at systemic pressure (to simulate
      percutaneous transluminal coronary angioplasty) in five dogs or regionally
      controlled blood cardioplegic reperfusion on bypass in five others to simulate
      coronary bypass. In five dogs ischemia was prolonged to 2 hours, and the initial
      reperfusate was blood cardioplegic solution on total vented bypass (to simulate
      primary coronary bypass). All hearts receiving simulated thrombolysis (100%)
      after 1 hour of ischemia had reperfusion-induced ventricular fibrillation. All
      hearts treated by simulated angioplasty recovered regional contractility (56% of
      control systolic shortening), whereas there was no (0%) recovery of spontaneous
      contractility after subsequent blood cardioplegic reperfusion, and only two (40%)
      dogs had contractile reserve capacity (6% +/- 49%). Conversely, surgically
      controlled blood cardioplegic reperfusion without preceding low-flow normal blood
      reperfusion after 2 hours of ischemia resulted in no ventricular arrhythmias (0%;
      p less than 0.05 versus simulated coronary artery bypass after simulated
      thrombolysis), 72% +/- 7% (p less than 0.05 versus simulated coronary artery
      bypass after simulated thrombolysis) recovery of regional contractility
      (ultrasonic crystals), and 114% +/- 11% (p less than 0.05 versus simulated
      coronary artery bypass after simulated thrombolysis) recovery of contractile
      reserve with calcium chloride stimulation. We conclude that controlled
      reperfusion (simulating coronary artery bypass) with blood cardioplegic solution
      produces immediate functional recovery and avoids the ventricular fibrillation
      that follows simulated thrombolysis despite the need for prolonged ischemic time.
      Preceding controlled reperfusion by normal blood reperfusion (simulated
      thrombolysis) shortens the ischemic time but nullifies immediate functional
      recovery possible by simulated coronary bypass and produces unnecessary
      arrhythmias.

PMID- 1999940
TI  - Differing susceptibilities to cold preservation of rat atria and ventricles.
AB  - The susceptibilities of atria and ventricles to cold preservation were studied in
      rat hearts. Rat hearts were stored in Collins' solution at 4 degrees C for 0, 12,
      or 24 hours, and the atrial and ventricular function was measured in a working
      heart model and in isolated atrial and papillary muscle preparations. In working
      heart preparations, cardiac output decreased to 0 ml/min and other parameters of
      ventricular function (systolic and end-diastolic pressure and dP/dt of the left
      ventricle) markedly deteriorated after 12 hours of preservation. After 24 hours,
      no contraction of the left ventricle was observed despite the presence of atrial
      contraction. In isolated atrial muscle preparations, the rate of spontaneous
      beating of the right atrium was not affected by cold preservation. The twitch
      contractions of right and left atria were attenuated but elicited after 24 hours.
      In electrically driven papillary muscles, twitch contractions were also markedly
      attenuated by 12 hours of preservation and were abolished after 24 hours. The
      positive inotropic effect of isoproterenol was also markedly attenuated in the
      atrial preparations by cold preservation. However, the positive chronotropic
      response to isoproterenol and the negative chronotropic and inotropic responses
      to carbachol were little affected by cold preservation. Intramural cholinergic
      and adrenergic nerve stimulation produced first negative and then positive
      effects on the beating rate and twitch contraction in the isolated right atria.
      Cold preservation selectively attenuated and finally abolished the adrenergic
      responses. In the ventricles, the adenosine triphosphate and creatine phosphate
      content significantly decreased and the lactate content increased with an
      increase in the preservation period. On the other hand, changes of such
      metabolites in the atria were either not observed or were much smaller. These
      results suggest that atrial function is maintained better than ventricular
      function in the cold-preserved heart.

PMID- 1999942
TI  - Intent-to-treat analysis and the problem of crossovers. An example from the
      Veterans Administration coronary bypass surgery study.
AB  - In randomized clinical trials of treatment for ischemic heart disease that
      compare medical with surgical treatment, many persons initially assigned to
      medical therapy eventually receive surgical intervention. For example, in the
      three major trials of bypass grafting for stable angina, crossover rates from
      medical to surgical therapy were approximately 25% at 5 years. For this reason,
      the classic intent-to-treat analyses have been criticized for their inability to
      evaluate the "true" effect of treatment. In this article we emphasize the concept
      of "initial treatment" as it applies to intent-to-treat analyses and examine four
      proposed alternative methods of analysis based on adherence with survival data
      from the Veterans Administration Cooperative Study to illustrate the concepts.
      The alternative methods include (1) censoring crossovers when treatment changes,
      (2) transferring crossovers from the original to the new treatment group when
      treatment changes, (3) excluding all crossovers from analysis, and (4) counting
      crossovers from the date of randomization in the treatment ultimately received
      group. We point out the biases attendant on analyses based on adherence and
      reaffirm the validity of intent-to-treat analysis.

PMID- 1999941
TI  - Absence of particle-induced coronary vasoconstriction during cardioplegic
      infusion: is it desirable to use a microfilter in the infusion line?
AB  - Many cardiac surgical units now use a microfilter in the infusion line for
      delivery of crystalloid cardioplegic solution to protect against the potential
      hazards of particulate contamination of cardioplegic solution. The aim of this
      group of studies was to determine the effects of particulate contamination of
      cardioplegic solutions, in order to establish whether a microfilter is needed in
      the infusion line. Total particle counts performed on two commercial cardioplegic
      solutions were low, but there were sufficient particles greater than 10 microns
      in diameter to cause coronary vasoconstriction. In isolated rat hearts a 20
      minute infusion of St. Thomas' Hospital cardioplegic solution produced a
      progressive reduction in coronary flow, which was not prevented by the inclusion
      of a 0.8 micron filter in the infusion line. Two studies were performed on canine
      hearts to determine the effects of unfiltered cardioplegic solution on coronary
      vascular resistance. In the first, cardioplegic solution at 20 degrees C was
      infused for 20 minutes at a constant pressure of 50 mm Hg and flow rate was
      measured. In the second, the same solution at 4 degrees C was infused at a
      constant flow rate for 2 1/2 minutes and the infusion pressure was measured. In
      neither study did coronary vascular resistance rise. A final clinical study
      involving patients undergoing coronary bypass surgery compared the effects on
      coronary resistance of infusion at a constant flow of filtered versus unfiltered
      cardioplegic solution (n = 10 in each group). There was a similar rise in
      coronary perfusion pressure in both groups during the infusion. We conclude that
      there is insufficient evidence of particle-induced coronary vasoconstriction to
      justify the expense of a microfilter in the cardioplegic infusion line.

PMID- 1999943
TI  - Discriminate use of electrocautery on the median sternotomy incision. A 0.16%
      wound infection rate.
AB  - Between June 1978 and June 1989, superficial or deep mediastinitis (or both)
      developed in only five (0.16%) of 3118 consecutive patients. All patients studied
      underwent cardiac procedures through a median sternotomy and survived more than 7
      postoperative days. The surgical team disciplined itself to divide presternal
      soft tissues with a scalpel and used electrocautery for pinpoint hemostasis only.
      This 0.16% infection rate was statistically significantly lower than those in 28
      previously published studies (Pearson's chi 2 test, p less than 0.05). Twenty
      four predisposing factors were evaluated by Fisher's exact test. Among these only
      an operating time longer than 3 hours is related to sternotomy infections (p =
      0.0208), and this effect was not a strong one. Statistical evidence strongly
      suggests that discriminate use of electrocautery is a major reason for the lowest
      median sternotomy infection rate reported to date.

PMID- 1999944
TI  - Mitral valve repair by replacement of chordae tendineae with
      polytetrafluoroethylene sutures.
AB  - Expanded polytetrafluoroethylene sutures have been used for replacement of
      diseased chordae tendineae during reconstructive procedures on the mitral valve
      in 43 patients. There were 28 men and 15 women whose mean age was 55 years, range
      21 to 76. Three fourths of the patients were in New York Heart Association class
      III or IV. Replacement of primary chordae tendineae of the anterior leaflet was
      performed with 4-0 or 5-0 polytetrafluoroethylene sutures. A double-armed suture
      was passed twice through the fibrous portion of the papillary muscle head and
      tied down. Each arm of the suture was brought up to the free margin of the
      leaflet and passed through the area where the native chorda was attached. After
      the lengths of the two arms were adjusted, the ends were tied together on the
      ventricular side of the leaflet. Thirty patients had degenerative disease of the
      mitral valve; the incompetence was due to prolapse of the anterior leaflet in 14
      patients and prolapse of the anterior and posterior leaflets in 16. Eleven
      patients had rheumatic mitral valve disease: four had stenosis, three had
      regurgitation, and four had mixed lesions. Two patients had ischemic mitral
      regurgitation caused by rupture of a papillary muscle head. There were no
      operative deaths. Patients have been followed up from 5 to 61 months, mean 13.
      Doppler echocardiographic studies were performed at regular intervals after the
      operation and revealed normal mitral valve function in most patients There were
      two failures that necessitated mitral valve replacement: one because of acute
      mitral regurgitation and the other because of hemolysis. There have been two late
      deaths, neither one valve related. Replacement of chordae tendineae with
      polytetrafluoroethylene sutures is simple and allows for reconstruction of the
      mitral valve in many patients who would otherwise require mitral valve
      replacement. Because our patients have been followed up for a limited time, the
      long-term results of this procedure remain unknown.

PMID- 1999945
TI  - Alcohol and pyruvate cardioplegia. Twenty-four-hour in situ preservation of
      hamster hearts.
AB  - Isolated hamster hearts were first perfused with a normal Krebs-Henseleit medium
      to demonstrate comparable viability of hearts before perfusing and storing them
      for 24 hours in one of three solutions. The three solutions were a physiologic
      saline with pyruvate as the substrate and 4% alcohol to arrest the heart (group
      1), a standard cardioplegic solution (group 2), and an alcohol-free physiologic
      saline with pyruvate as the substrate (group 3). Recovery in terms of
      rate/pressure product and oxygen consumption after 30 minutes of reperfusion was
      81% and 93%, respectively, for group 1, 13% and 32% for group 2, and 70% and 72%
      for group 3. Percent of physiologic recovery was not related to recovery of
      adenosine triphosphate. The adenosine triphosphate level returned to
      approximately 40% control level in all three groups, and in all three groups
      inorganic phosphate remained approximately 320% over control level after 30
      minutes of reperfusion. Phosphocreatine level significantly higher in groups 1
      and 3 than in group 2, as a result of improved oxygen consumption. Intracellular
      pH, determined by phosphorous 31 nuclear magnetic resonance spectroscopy, was
      physiologic in groups 1 and 3 but alkaline in group 2. This alkalinity may have
      been caused by leaky membranes. Pyruvate helped preserve mitochondrial function
      during depressed oxygen delivery, such as was seen during the 24-hour storage
      period. Four percent alcohol arrested the heart; combined with pyruvate plus
      alcohol solution were better than a standard cardioplegic solution for
      maintaining functional capability.

PMID- 1999946
TI  - The dynamics of antegrade cardioplegia with simultaneous coronary sinus
      occlusion. Effects on aortic root infusion pressure, coronary sinus pressure, and
      myocardial cooling.
AB  - It has been suggested that antegrade cardioplegia with coronary sinus occlusion
      improves homogeneous myocardial cooling and reduces myocardial injury in the
      presence of coronary artery occlusion. Little data are available on the exact
      relationships among the basic elements or this intervention, including antegrade
      infusion rate, aortic root pressure, the degree of coronary sinus occlusion,
      coronary sinus pressure, and myocardial cooling. The purpose of this study was to
      determine these relationships and to provide some basic guidelines for better
      understanding of this intervention. Twenty-two sheep were placed on
      cardiopulmonary bypass, the distal left anterior descending artery was occluded,
      and the proximal coronary sinus was snared. Sixteen combinations of infusion rate
      (3, 5, 7, or 9 ml/kg/min) and coronary sinus occlusion (total, subtotal, or
      moderate occlusion or no occlusion) were adopted for each 2 minutes of antegrade
      cardioplegia, yielding 96 measurements. Myocardial temperatures in the occluded
      and nonoccluded regions, aortic root infusion pressure, and coronary sinus
      pressure were measured during each infusion of cardioplegic solution. Coronary
      sinus occlusion was then released, and the whole heart was reperfused for 30
      minutes for another infusion of cardioplegic solution and measurements. Results
      showed good degrees of linearity between infusion rate and aortic root infusion
      pressure for all coronary sinus occlusion and noninfusion groups (p less than
      0.01). A positive effect of coronary sinus occlusion on aortic root infusion
      pressure was observed. The graded increases in infusion rate with various degrees
      of coronary sinus occlusion were constantly associated with elevation of coronary
      sinus pressure (p less than 0.01). It was also noted that myocardial temperatures
      in the region of the occluded left anterior descending artery were significantly
      lower in coronary sinus occlusion groups than in nonocclusion groups (p less than
      0.01 or 0.05). Myocardial temperature in the nonoccluded region decreased
      significantly with the stepwise increases in infusion rate (p less than 0.01),
      but not with the increases in coronary sinus occlusion (not significant). Based
      on this and previous studies, we recommend that the induced coronary sinus
      pressure be safely maintained in the range of 25 to 35 mm Hg and that further
      studies be focused on the infusion rate of 5 ml/kg/min with subtotal or total
      coronary sinus occlusion for the intervention of antegrade cardioplegia plus
      coronary sinus occlusion.

PMID- 1999947
TI  - Critical aortic stenosis in early infancy. Anatomic and echocardiographic
      substrates of successful open valvotomy.
AB  - To establish noninvasive criteria by which to manage infants with critical aortic
      stenosis, we examined 20 heart specimens from infants under 3 months of age and
      reviewed the clinical course and real time echocardiograms of 20 patients in the
      same age group. All 20 infants underwent open valvotomy, and in five cases both
      echocardiographic and postmortem measurements were available for the same heart.
      The anatomic specimens showed a spectrum of valvular, ventricular, and vascular
      abnormalities that could be accurately identified by echocardiography. A small
      left ventricular cavity was usually associated with a narrow ventriculoarterial
      junction, small ascending aorta, and narrow subaortic region. In these hearts,
      the mitral valve had a single or grossly hypoplastic papillary muscle with short
      or "arcuate" tendinous cords. A dilated left ventricular cavity had wider inflow
      and outflow orifices, and the tension apparatus of the mitral valve was either
      normal or supported by hypertrophic papillary muscles, at the other end of the
      spectrum. The survivors (n = 15) and nonsurvivors (n = 5) of open valvotomy
      showed significant differences in the echocardiographic dimensions of the left
      ventricle (p less than 0.005), the subaortic region (p less than 0.05), the
      ventriculoaortic junction (p less than 0.05), the ascending aorta (p less than
      0.005), and the mitral valve orifice (p less than 0.001). Moreover, the papillary
      muscle of the mitral valve was invariably single or hypoplastic with short
      tendinous cords in the early nonsurvivors. Infants with unfavorable cardiac
      anatomy tended to present earlier (p less than 0.05) and to have a lower systemic
      blood pressure (p less than 0.05), and they required prostaglandin E2 to maintain
      right ventricular support of the circulation through a persistent arterial duct.
      This study suggests that patients with a small left ventricle (echocardiographic
      inflow dimension less than 25 mm), a narrow ventriculoaortic junction (less than
      5 mm), and a small mitral valve orifice (less than 9 mm) will not achieve a
      satisfactory surgical result from aortic valvotomy. Such patients should be
      considered for cardiac transplantation or the Norwood-type of palliation for
      hypoplastic left heart syndrome.

PMID- 1999948
TI  - Esophageal ultrasound and the preoperative staging of carcinoma of the esophagus.
AB  - Esophageal ultrasound allows the esophageal wall to be viewed as five discrete
      layers. Lymph nodes are easily identified, and their size, shape, margin, and
      internal structure can be assessed. This provides an alternative method of
      preoperative (clinical) evaluation of the primary tumor [T] and the regional
      lymph nodes [N] of patients with carcinoma of the esophagus. Esophageal
      ultrasound was attempted in the clinical staging of 28 patients with carcinoma of
      the esophagus. Six patients (21%) were not assessed because of the inability to
      pass the esophageal ultrasound probe through the malignant stricture. The staging
      system for carcinoma of the esophagus developed by the International Union
      Against Cancer and the American Joint Committee on Cancer was used. Twenty-two
      patients had the true T determined by pathologic review of the resected
      esophagus. Esophageal ultrasound correctly identified T in 13 patients (59%
      accuracy). In four patients (18%) the disease was overstaged by esophageal
      ultrasound; all these patients had early T1 tumors confined to the submucosa. In
      five patients (23%) the disease was understaged by esophageal ultrasound; all of
      these patients had advanced tumors (four T3 and one T4) that invaded beyond the
      esophageal wall. Seven of the nine incorrect esophageal ultrasound determinations
      were called T2 (three T1, three T3, one T4), which suggests that the borders of
      the muscularis propria require careful attention when evaluated by esophageal
      ultrasound. Twenty patients had the true N determined by pathologic review of the
      resected specimen. Esophageal ultrasound correctly identified N in 14 patients
      (70% accuracy). Three patients were falsely identified as having N1 disease and
      three were falsely identified as having N0 disease. The sensitivity, specificity,
      positive predictive value, and negative predictive value for N assessment by
      esophageal ultrasound were 70%. Esophageal ultrasound provides an alternative
      method of visualization of the esophageal wall and regional lymph nodes. Our
      early experience shows promise for esophageal ultrasound in the clinical staging
      of carcinoma of the esophagus.

PMID- 1999950
TI  - Diagnosis of traumatic aortic rupture by transesophageal echocardiography.

PMID- 1999949
TI  - Freehand allograft aortic valve replacement and aortic root replacement. Utility
      of intraoperative echocardiography and Doppler color flow mapping.
AB  - Seventeen consecutive patients undergoing 20 planned aortic valve replacements
      with allograft valves at Stanford University Medical Center were studied with
      intraoperative epicardial echocardiography and Doppler color flow mapping before
      and after cardiopulmonary bypass. Native aortic valves were replaced in 12 of the
      20 patients, and eight patients underwent second aortic valve procedures. In 17
      of 20 patients allograft selection was guided by prebypass echocardiographic
      estimates of annular diameter and/or length of allograft aortic root required.
      Other prebypass findings included unanticipated severe mitral regurgitation in
      one patient (which precluded allograft aortic valve replacement), left-to-right
      shunts in five patients, ascending aortic dissection in one, and aortic root
      disease necessitating coronary reimplantation or bypass in two. Postbypass
      echocardiography demonstrated acceptable competency of 18 of 19 allograft valves
      (mild or no aortic insufficiency). Postbypass echocardiography also documented
      successful repair of four of five shunts and mild mitral regurgitation in 15 of
      19 patients (versus 11 of 19 before bypass). CONCLUSIONS: Intraoperative
      echocardiography-Doppler mapping is a useful adjunct for allograft aortic valve
      or aortic root replacement; it allows confident selection of appropriate tissue
      size before aortic cross clamping, which minimizes delay from allograft thawing
      procedures. It also provides helpful information about the extent of aortic root
      disease and coronary ostial anatomy before bypass, confirms allograft competency
      after bypass, and detects accompanying valvular and other hemodynamic lesions
      before and after allograft valve replacement.

PMID- 1999952
TI  - Invited letter concerning: anticoagulant plus platelet inhibitor therapy in
      patients with mechanical valve prostheses.

PMID- 1999951
TI  - Intraoperative transesophageal echocardiography and periprosthetic leaks.

PMID- 1999953
TI  - Invited letter concerning: changes in myocardial high-energy stores and
      carbohydrate metabolism during intermittent aortic crossclamping in dogs on
      cardiopulmonary bypass at 34 degrees and 25 degrees C.

PMID- 1999954
TI  - Invited letter concerning: informed consent for blood transfusion.

PMID- 1999955
TI  - Serum interleukin-2 (IL-2), soluble IL-2 receptors and tumor necrosis factor-alfa
      levels are significantly increased in acute myeloid leukemia patients.
AB  - Serum interleukin-2 (IL-2), soluble IL-2 receptors (sIL-2R) and tumor necrosis
      factor-alfa (TNF-alpha) levels were determined in 66 previously untreated
      consecutive patients with acute myeloid leukemia (AML) and in 22 normal
      volunteers. The following mean (+/- SE) values were observed in patients and
      controls, respectively: 35 +/- 14.7 (range 0.5-500) and 0.7 +/- 0.02 (0.5-0.8
      U/ml for IL-2 (p = 0.001); 1622 +/- 289 (110-10,600) and 422 +/- 30 (207-666)
      U/ml for sIL-2R (p = 0.0001); 1247 +/- 196 (218-4672) and 152 +/- 11 (75-308)
      pg/ml for TNF-alpha (p = 0.0001). With respect to the FAB classification system,
      we found a significantly different distribution of serum IL-2 mean values in
      distinct subcategories, i.e. 3.4 +/- 1.9 U/ml in M1-M2-M3 and 42.4 +/- 20.4 U/ml
      in M4-M5 subgroups, respectively (p = 0.01), whereas sIL-2R and TNF-alpha levels
      were 1144 +/- 322 U/ml and 1120 +/- 317 pg/ml in M1-M2-M3 patients and 1945 +/-
      317 U/ml and 1270 +/- 259 pg/ml in the M4-M5 group. A significantly positive
      correlation between TNF-alpha and sIL-2R (r = 0.53; p = 0.002) was also detected
      in the M4-M5 group. Sixty-three out of 66 patients received an intensive
      chemotherapy program. Univariate analysis showed that age and sIL-2R greater than
      2000 U/ml significantly affected both complete remission rate and overall
      survival, whereas by multivariate analysis, age was the only independent variable
      significantly influencing survival. These data confirm recent in vitro evidence
      suggesting the role of IL-2, sIL-2R, and TNF-alpha in the control of normal
      hematopoiesis and leukemogenesis. Since the availability of recombinant cytokines
      for clinical use in AML, it is crucial to understand their spectrum of
      interaction in order to select the appropriate combination for in vivo
      administration.

PMID- 1999956
TI  - Molecular investigation of 19p13 in standard and variant translocations: the E12
      probe recognizes the 19p13 breakpoint in cases with t(1;19) and acute leukemia
      other than pre-B immunophenotype.
AB  - The gene E2A has recently been cloned, mapped to 19p13 and shown to be rearranged
      in cases of pre-B acute lymphoblastic leukemia (ALL) with t(1;19) (q23;p13). Nine
      cases with a 19p13 breakpoint, four having a phenotype other than pre-B, have
      been investigated with the E12 probe to the E2A gene. Five cases had t(1;19)
      (q23;p13) and C-ALL with pre-B phenotype in four out of four cases tested. Two
      cases had t(1;19) (q21;p13), one with Null cell phenotype, t(4;11), and 'jumping
      translocations' and the other with acute non-lymphocytic leukemia M5 following
      bone marrow transplantation for C-ALL. Variant translocations in patients with
      ALL were t(15;19) (q15;p13) and t(17;19) (q21;p13). Southern blotting with E12
      showed rearrangement in the cases with t(1;19) (q23;p13) and t(1;19) (q21;p13),
      but not in other cases with variant 19p13 breakpoints. Thus rearrangement of the
      E2A gene is not restricted to cases with pre-B ALL but may also occur in acute
      leukemias with other immunological phenotypes. Failure to detect rearrangement in
      19p13 variants may be due to an E2A breakpoint outside the E12 recognition
      region. Alternatively, there may be further genes in this location with relevance
      to leukemogenesis.

PMID- 1999957
TI  - Expression of a novel surface antigen MKW in childhood acute leukemia has
      prognostic significance.
AB  - A monoclonal antibody (MoAB) has been developed which reacts with a previously
      unidentified hematopoietic cell surface protein called MKW. This MoAB (anti-MKW)
      does not cluster with antibodies in any of the known cluster groups of
      differentiation. Blast cell expression of MKW was studied in 196 consecutively
      diagnosed children with acute lymphoblastic leukemia (ALL), 69 children with
      previously untreated acute myeloblastic leukemia (AML) and four children with
      secondary AML. MKW expression, clinical, laboratory and cytogenetic features at
      diagnosis, and treatment response and duration were examined for significant
      correlations. MKW was expressed on blasts from 12.8% of children with ALL and
      24.6% of children with de novo AML. The expression of MKW appears to be more
      common in patients with secondary AML (three of four) than de novo AML (17 of
      69). In patients with AML, the expression of MKW was correlated with an elevated
      initial leukocyte count (p = 0.0005) and poorer disease-free survival (p = 0.04).
      In patients with ALL, the expression of MKW was associated with a lower
      hemoglobin level (p less than 0.05) and a lower complete remission rate (p =
      0.02). At a median follow-up of 4.6 years ALL patients with greater than or equal
      to 50% MKW+ blasts had a poorer event-free survival (EFS) than both MKW+ patients
      with 25-49% positive blasts (p = 0.03) and MKW+ patients (p = 0.0001). The
      disease-free survival was also poorer for ALL patients with greater than or equal
      to 50% MKW+ blasts (p = 0.02). In Cox regression analysis, the expression of MKW
      had an independent prognostic significance in children with ALL. As MKW is a
      unique cell surface antigen and its expression has prognostic significance in
      acute leukemias in children, further study in a larger series of patients is
      warranted.

PMID- 1999958
TI  - Pleural effusion is associated with a poor treatment outcome in stage III small
      non-cleaved cell lymphoma.
AB  - The clinical significance of pleural effusion was assessed in 24 children with
      unresectable abdominal small non-cleaved cell lymphoma (St. Jude Stage III).
      Patients were consecutively enrolled and treated on a regimen including high dose
      fractionated cyclophosphamide and co-ordinated high dose methotrexate and
      cytarabine. The overall results were excellent, with 20 of 24 patients alive and
      event-free at a median follow-up of 4 years. Only one of the patients who lacked
      pleural effusion has relapsed (testicular), even though many had massive disease.
      In contrast, three of seven patients with pleural effusion have failed treatment
      (p = 0.02) and subsequently died. Two measures of tumor burden, serum lactic
      dehydrogenase and, in a subset of patients, interleukin-2-receptor levels, were
      significantly higher in patients with pleural effusion (p = 0.002 and p = 0.05,
      respectively). These findings suggest that unresectable abdominal small non
      cleaved cell lymphoma associated with pleural effusion should be up-staged and
      that these patients should receive more intensive chemotherapy.

PMID- 1999960
TI  - Translocations t(14;18) and t(8;14) with rearranged bcl-2 and c-myc in a case
      presenting as B-ALL (L3).
AB  - Follicular lymphoma is a low grade malignancy characterized by the translocation
      t(14;18), which involves the putative oncogene bcl-2. We describe a 73-year-old
      patient presenting with Burkitt acute lymphoblastic leukemia (B-ALL) L3 (Burkitt
      type), whose cells had the following immunophenotype: CD19+, CD22+, HLA-DR+,
      CD10+, TdT-, Cyt IgM-, CD34-. Analysis of 25 peripheral blood metaphases showed
      the presence of t(14;18) (q32;q21), and t(8;14) (q24;q32) in 24 cells and
      t(14;18) only in one cell, suggesting that the latter translocation came first
      during clonal evolution. Both bcl-2 and c-myc were rearranged in addition to the
      immunoglobulin heavy and light chain genes. The presence of small lymphoid cells
      in paratrabecular areas on the bone marrow biopsy, together with evidence of
      cytogenetic clonal evolution, was indicative of a transformation from a low grade
      follicular lymphoma to a more aggressive Burkitt type malignancy.

PMID- 1999959
TI  - Effect of rhCSF-1 on human hemopoiesis in long-term cultures from patients with
      acute myelogenous leukemia.
AB  - Bone marrow and/or peripheral blood cells from seven patients with acute
      myelogenous leukemia (AML) were maintained for 7 weeks in Dexter-type long-term
      culture (LTC) in order to study the effect of exogenous recombinant human colony
      stimulating factor-1 (rhCSF-1) and to quantitate endogenous levels of CSF-1.
      rhCSF-1 was added every 2 days during the first 3 weeks of culture at 15 ng/ml.
      In all but one culture, adding rhCSF-1 inhibited putative leukemic hemopoiesis
      [i.e. decreased numbers of abnormal (blast) colony-forming cells and blasts] and
      stimulated putative normal hemopoiesis (increased numbers of CFU-GM and
      macrophages). Our data, however, do not distinguish direct effects of rhCSF-1 on
      normal or leukemic cells from indirect effects mediated by accessory cells. In
      cultures with a poorly formed adherent layer (all derived from patients
      classified as M5), the endogenous levels of CSF-1 were lower than those in
      cultures with a good (confluent) adherent layer, indicating that the levels of
      CSF-1 in LTC from AML patients positively correlate with the formation of the
      adherent layer. Our data indicate that CSF-1 is an important modulator of human
      hemopoiesis in LTC established from AML bone marrow or peripheral blood, and that
      rhCSF-1 might be valuable for purging leukemic cells in LTC established from AML
      patients' bone marrow or peripheral blood for autologous transplantation.

PMID- 1999961
TI  - Functional and molecular characteristics of acute lymphoblastic leukemia cells
      with a mature T-cell phenotype from a patient with ataxia telangiectasia.
AB  - A 12-year-old male patient with ataxia telangiectasia developed an acute
      lymphoblastic leukemia of T-cell phenotype. The lymphoblasts showed uniform
      surface expression of CD3, CD7, CD8, and T-cell receptor (TCR) alpha/beta chains,
      positive immunofluorescent staining of terminal deoxynucleotidyl transferase,
      complex cytogenetic aberrations including t(14;14) (q11;q32) and unique
      rearrangements of TCR beta and gamma chain genes, indicating the clonal expansion
      of leukemic cells. CD25 expression could be readily induced on the leukemic cells
      by mitogenic stimulation, followed by CD71 expression, but interleukin-2
      production and subsequent proliferation in response to mitogens were subnormal.

PMID- 1999962
TI  - Effect of cryopreservation on colony-forming ability and self-renewal capacity of
      human leukemic progenitor cells in vitro.

PMID- 1999963
TI  - [The quality of surgery can be retained and further developed].

PMID- 1999964
TI  - [How much calcium do we need in our diet?].

PMID- 1999965
TI  - [Diagnosis and treatment of giant cell arteritis].

PMID- 1999966
TI  - [Do we really have sufficient answers to cholesterol questions?].

PMID- 1999967
TI  - [Double message from the authorities on influenza vaccine].

PMID- 1999968
TI  - [Cleaning with chlorine--a method for disinfection of injection instruments].

PMID- 1999969
TI  - [Leukocyte adhesion: a fundamental process in immunologic and inflammatory
      reactions].
AB  - Adhesion to cells and extracellular matrices is a fundamental feature of
      leukocyte physiology, a process crucial to the generation of immune and
      inflammatory responses. Adhesive interactions between lymphocytes,
      monocytes/macrophages, granulocytes and vascular endothelial cells are mediated
      by specific cell-adhesion molecules (CAMs). The Leu-CAMs (CD111/CD18) belong to a
      large family of cell-surface molecules known as intergrins, a family which also
      includes receptors for extracellular matrix components. In man, inherited
      deficiency of Leu-CAMs is characterised by recurrent, sometimes fatal, bacterial
      infections. In animals, on the other hand, Leu-CAM blocking by monoclonal
      antibodies has been found beneficial in inflammatory disorders. As some lymphoid
      malignancies are devoid of CAMs, it is possible that their absence may be a
      contributing factor in the development of leukaemia and lymphoma.

PMID- 1999970
TI  - [Duodenal adenoma--not only a curiosity].

PMID- 1999971
TI  - [Atherosclerosis--the molecular background].
AB  - The clinical manifestations of atherosclerosis, such as stroke and coronary heart
      disease, are the major cause of death and disability in the western world. Recent
      technological progress in cell and molecular biology have provided new
      opportunities of studying the basic biological mechanisms involved in
      atherogenesis. Several lines of evidence suggest that the macrophage accumulation
      of cholesterol in atherosclerotic plaques occur as a result of lipid
      peroxidation. Macrophages lack a receptor for normal low density lipoprotein
      (LDL), but express a high affinity receptor for oxidized LDL - the scavenger
      receptor. Oxidized LDL has also been found to be cytotoxic to endothelial cells
      and to promote the adhesion of monocytes to the endothelium. Growth in plaque
      size is chiefly due to a proliferation of smooth muscle cells. Studies using a
      variety of hybridization techniques have demonstrated expression of different
      growth factor genes in atherosclerotic plaques. It has also been shown that
      cultured smooth muscle cells have the capacity to produce growth factors, and
      that this production is subject to factors associated with known risk factors for
      cardiovascular disease.

PMID- 1999972
TI  - [Influenza vaccination--an appreciated activity with doubtful effect].

PMID- 1999974
TI  - [Bone-anchored hearing aids and implants in the cochlea improve hearing].

PMID- 1999973
TI  - [Titanium has renewed oral surgery. Are ceramics the materials of the future?].

PMID- 1999975
TI  - [Glucophage and lactic acidosis].

PMID- 1999976
TI  - [Bjorkaska--esophageal ulceration].

PMID- 1999977
TI  - [Q fever occurs even in Sweden].

PMID- 1999979
TI  - [Evaluation of the restructuring of psychiatry--questions, possibilities and
      conditions].

PMID- 1999978
TI  - [The Danish trial with non-prescription drugs against stomach ulcer evaluated. An
      internationally unique drug reform caused a stagnant sale of drugs against
      stomach ulcer].

PMID- 1999980
TI  - [Political and administrative crisis intervention is needed in psychiatric
      occupational rehabilitation].

PMID- 1999981
TI  - [The abortion law is not questioned because of general advice concerning the
      fetus!].

PMID- 1999982
TI  - [Cataract surgery--an important field for quality assurance work].

PMID- 1999983
TI  - [Coronary vessel radiography in Sweden. Well-planned decentralization is
      desirable].

PMID- 1999984
TI  - [Giving objective information on radiation risks should be ethically obvious].

PMID- 1999985
TI  - [To control one's own anxiety does not need to be called abuse].

PMID- 1999986
TI  - [It is unwise to give unrestricted vaccination advice].

PMID- 1999987
TI  - [Pacemaker, quality control and loyal cooperation].

PMID- 1999988
TI  - [New discoveries on alcohol effects on the fetus were presented at an
      international meeting].

PMID- 1999989
TI  - [Computer support improves control and monitoring of patients with rheumatism
      during remission treatment].

PMID- 1999990
TI  - [Increased incidence of malignant lymphoma in HIV-infected persons].

PMID- 1999991
TI  - [Good American experiences with early rehabilitation of occupational injuries].

PMID- 1999992
TI  - [Compulsory isolation of HIV-infected patients is a question of principle for the
      entire health care system].

PMID- 1999993
TI  - [Low number of surgical interventions threatens the quality of surgery].

PMID- 1999994
TI  - [Echocardiography yesterday, today and tomorrow].

PMID- 1999995
TI  - [Courses for family members of psychiatric patients].

PMID- 1999996
TI  - [Psychiatric clinics for the elderly need sufficient resources for ambulatory
      care].

PMID- 1999997
TI  - [CNS hemorrhage after drug induced thrombolysis in suspected myocardial
      infarction].

PMID- 1999998
TI  - [Changing of feeding schedules resulted in prolonged breast feeding period].

PMID- 1999999
TI  - [Perilunar luxation--an unusual injury demanding immediate and correct
      treatment].

PMID- 2000000
TI  - [Cyclosporin as a cause of hypertension in patients with heart transplantation].

PMID- 2000001
TI  - [All patients with acute epiglottitis must be observed in intensive care units].

PMID- 2000002
TI  - [Ubiquinone, the unknown sibling of cholesterol, as a member of the antioxidant
      group].

PMID- 2000003
TI  - [Only the right diet can be effective for a woman with Crohn disease].

PMID- 2000004
TI  - [Fetal and neonatal thyrotoxicosis are severe conditions in which diagnosis can
      be overlooked].

PMID- 2000005
TI  - [Tricyclic antidepressive agents are effective in the treatment of sleep
      disorders among torture and war victims].

PMID- 2000007
TI  - [Habitual somatizing (2). Treatment is a contract between physician and patient].

PMID- 2000006
TI  - [Habitual somatizing (1). Non-traditional patient-physician relation in
      pychophysiologic disorders].

PMID- 2000008
TI  - Argon laser stapedotomy.
AB  - Lasers have been used in otology for 10 years. There have been reports of
      excellent hearing results using laser energy in surgery for otosclerosis. We used
      the argon laser in 75 consecutive primary stapedotomy procedures. The
      postoperative air-bone gap was 10 dB or less in 87% of patients and 20 dB or less
      in 95%. One ear (1.5%) had no postoperative hearing secondary to a granulomatous
      reaction. Complications were otherwise uncommon and mild. Most patients were
      treated on an outpatient basis. Our results compare favorably with other reports
      of laser surgery for otosclerosis. We conclude that excellent hearing results can
      be obtained using the argon laser for stapedotomy procedures.

PMID- 2000009
TI  - Intracranial complications of paranasal sinusitis: a combined institutional
      review.
AB  - Intracranial complications of paranasal sinusitis constitute true surgical and
      medical emergencies. The charts of all patients (n = 649) admitted for acute or
      chronic sinusitis to the University of Minnesota Hospital and to the University
      of Michigan Medical Center during a 13-year period (1975 to 1988) were
      retrospectively reviewed to determine the incidence of complications. The
      clinical presentation, bacteriology, involved sinuses, influencing host factors,
      white blood cell count on presentation, length of hospitalization, and
      postinterventional complications are presented. Twenty-four patients with
      intracranial complications from paranasal sinusitis are studied for an incidence
      of 3.7%. Aggressive medical and semi-emergent surgical intervention are required
      to prevent excessive morbidity and/or mortality. Intracranial complications
      included subdural empyema, frontal lobe abscesses, intrahemispheric abscesses,
      cavernous and superior sagittal sinus thrombosis, and osteomyelitis.

PMID- 2000011
TI  - Fine-needle aspiration biopsy of salivary glands.
AB  - Between January 1, 1973, and December 31, 1988, the authors or their associates
      performed 552 fine-needle aspiration biopsies on patients with clinically
      significant masses of the salivary glands. All patients presented at the Medical
      College of Virginia Hospitals or Clinics of Virginia Commonwealth University;
      they were followed for periods ranging from 1 to 16 years. When available, the
      fine-needle aspiration diagnoses were correlated with histologic diagnoses and
      long-term patient outcomes. The sensitivity for a neoplasm was 93.3%; the
      specificity for the absence of a neoplasm was 99%. Diagnostic efficiency was
      96.4%, and predictive value of a positive aspiration for a neoplasm was 98.3%.
      With fine-needle aspiration, surgical excision of salivary gland masses is often
      unnecessary. In patients with primary and metastatic neoplasms involving the
      salivary glands, fine-needle aspiration aids the surgeon in mapping the extent of
      the surgical procedure and in preoperatively preparing the patient. The procedure
      is cost-effective.

PMID- 2000010
TI  - Prognostic factors in craniofacial surgery.
AB  - From 1979 to 1989, 21 patients underwent craniofacial resection for malignancies
      involving the anterior skull base. Histologic types included 8 squamous cell
      carcinomas, 3 chondrosarcomas, 2 melanomas, 2 basal cell carcinomas, 2
      adenocarcinomas, 2 poorly differentiated carcinomas, 1 malignant schwannoma, and
      1 malignant hemangiopericytoma. Survival was 57%, with follow-up of 41 months. A
      50% complication rate included osteomyelitis, cerebrospinal fluid rhinorrhea,
      meningitis, brain abscess, epidural abscess, and syndrome of inappropriate
      antidiuretic hormone. Recurrent disease occurred in 9 patients (41%), the most
      reliable predictor being dural invasion indicated preoperatively by CT scan or at
      operation. Patients demonstrating dural involvement (N = 9) had a 22% survival
      rate, while patients without (N = 12) had a survival rate of 83%. The impact of
      dural invasion on long-term survival is emphasized. Though complications were
      frequent, long-term results were favorable.

PMID- 2000012
TI  - Cerebrospinal fluid fistula and endoscopic sinus surgery.
AB  - Seven cases of cerebrospinal fluid fistulae occurring as a result of endoscopic
      sinus surgery in a total of 800 ethmoidectomies are discussed, along with 1 case
      referred for consultation. One cerebrospinal fluid fistula was intrasphenoid, 4
      were posterior ethmoid/base of skull, 2 were anterior ethmoid, and 1 was ethmoid
      cribriform. Six of 8 fistulae were closed endoscopically. The sphenoid sinus
      cerebrospinal fluid fistula was closed successfully with fibrin glue and Gelfoam.
      Five cerebrospinal fluid fistulae were closed successfully using fascia, muscle,
      and Gel-foam. Two cerebrospinal fluid fistulae were treated conservatively, and
      only 1 stopped. Anatomic and technical aspects related to the occurrence of
      cerebrospinal fluid fistulae are discussed. Management and treatment of
      cerebrospinal fluid fistulae occurring during and after endoscopic sinus surgery
      is emphasized. When identified intraoperatively or delayed, cerebrospinal fluid
      fistulae can be managed successfully by endoscopic technique.

PMID- 2000013
TI  - The internal oblique-iliac crest free flap in composite defects of the oral
      cavity involving bone, skin, and mucosa.
AB  - The reconstruction of oromandibular defects following ablative surgery is a
      challenging undertaking. When the defect involves skin as well as mucosa, the
      challenge becomes even greater. The internal oblique iliac crest
      osteomyocutaneous free flap is particularly useful for reconstruction of through
      and-through composite defects due to the inclusion of two separate soft-tissue
      flaps on the same vascular pedicle. We report our experience with this flap in
      the reconstruction of 10 patients with such defects. The utility, and the
      limitations of this form of reconstruction are discussed in detail.

PMID- 2000014
TI  - The response to human rIL-1, rIL-2, and rTNF in the middle ear of guinea pigs.
AB  - Human recombinant interleukin 1 (rIL-1), interleukin 2 (rIL-2), or tumor necrosis
      factor (rTNF) were injected transtympanically into the middle ear of normal
      guinea pigs. Effusion volume and cellular content were determined after sacrifice
      and rapid dissection of the ear. By 24 hours, rIL-2 (100 U) had produced a
      cellular effusion (77% to 92% polymorphonuclear neutrophil leukocytes), which
      cleared by 72 hours. rTNF (10 U) yielded a cellular effusion (12% to 67%
      lymphocytes) at 24 hours, which cleared by 48 hours. rIL-1 (100 U) did not
      produce significant effusion when compared to control. rIL-2 and rTNF cause an
      inflammatory effusion in the middle ear. To the extent they are generated in the
      middle ear during otitis media, these cytokines have the potential to contribute
      to the pathogenesis of otitis media with effusion.

PMID- 2000015
TI  - Dimensions and resistances of the human nose: racial differences.
AB  - Dimensions of the external nose and nostrils and nasal airflow resistances were
      determined in healthy, young Caucasian, Oriental, and Negro adults. Statistically
      significant variation between racial groups was found in nasal width and the
      differential between dorsi-ventral and transverse nostril diameters.
      Corresponding differences were found also in nasal airflow resistances of
      combined and separate nasal cavities in both the untreated and decongested state.
      Caucasian noses were leptorrhine, Negro noses were platyrrhine, and Oriental
      noses were of intermediate dimension. Mean nasal resistances of untreated noses
      were 0.129 Pa/cm3/sec in Negroes (N = 17), 0.146 in Orientals (N = 20), and 0.184
      in Caucasians (N = 24), and differences were more marked when noses were
      decongested (P less than 0.05 in all cases). Ratios between resistances of
      untreated and decongested noses showed no statistical differences between racial
      groups, suggesting a similarity in the mucovascular component of resistances.

PMID- 2000016
TI  - Functional use of the Nucleus 22-channel cochlear implant in the elderly.
AB  - A questionnaire was sent to 101 Nucleus 22-channel cochlear implant recipients
      aged 65 years and older to investigate the perceived impact of cochlear
      implantation on their quality of life. The questionnaire was designed to gain
      insight into the patient's daily use of the Nucleus implant. Sixty-seven
      questionnaires were returned over a 3-month period. The results of the survey
      showed that elderly cochlear implant patients obtained similar benefits to
      younger adult patients who were implanted with the same device. We believe that
      the results of this study will aid other centers when counseling elderly patients
      on the expected daily functional benefits of this device.

PMID- 2000017
TI  - Aerobic and anaerobic microbiology of peritonsillar abscess.
AB  - Thirty-four aspirates of pus from peritonsillar abscesses that were studied for
      aerobic and anaerobic bacteria showed bacterial growth. A total 107 bacterial
      isolates (58 anaerobic and 49 aerobic and facultative) were recovered, accounting
      for 3.1 isolates per specimen (1.7 anaerobic and 1.4 aerobic and facultatives).
      Anaerobic bacteria only were present in 6 (18%) patients, aerobic and
      facultatives in 2 (6%), and mixed aerobic and anaerobic flora in 26 (76%). Single
      bacterial isolates were recovered in 4 infections, 2 of which were Streptococcus
      pyogenes and 2 were anaerobic bacteria. The predominant bacterial isolates were
      Staphylococcus aureus (6 isolates), Bacteroides sp (21 isolates, including 15
      Bacteroides melaninogenicus group), and Peptostreptococcus sp (16) and S.
      pyogenes (10). beta-Lactamase-producing organisms were recovered from 13 (52%) of
      25 specimens tested. This retrospective study highlights the polymicrobial nature
      and importance of anaerobic bacteria in peritonsillar abscess.

PMID- 2000018
TI  - The effect of indoor air pollutants on otitis media and asthma in children.
AB  - This case-control study investigated the possible association between home
      environmental air pollutants and their effect on otitis media and asthma in
      children. Patients with physician-diagnosed otitis (n = 125, 74% response), with
      asthma (n = 137, 80% response), and controls (n = 237, 72% response) from a
      private pediatric practice seen between October 1986 and May 1987 were studied. A
      questionnaire inquired about housing characteristics (i.e., age, insulation,
      heating system) and sources of indoor air pollution such as cigarette smoking,
      use of woodburning stoves, household pets, etc. Analysis of the responses
      confirmed previous findings of significant relationships between maternal smoking
      (P = .021), and the presence of pets (P = .034) and the occurrence of asthma. A
      newly reported relationship between exposure to woodburning stoves and the
      occurrence of otitis (P less than .05) was reported. This implicates yet another
      risk factor (wood burning) in the etiology of otitis media.

PMID- 2000019
TI  - Gas composition and pressure in the middle ear: a model for the physiological
      steady state.
AB  - The gas contents of the physiological middle ear periodically cycle through two
      phases in steady state. During phase I, the eustachian tube is shut and the
      middle ear gas space is effectively closed. Gas is absorbed or produced at the
      mucosal surface, and the total pressure changes correspondingly. During phase II,
      which is of very short duration, the eustachian tube opens, a bolus of gas passes
      between the middle ear and the nasopharynx, and the total pressure in the middle
      ear rapidly adjusts to that in the nasopharynx. Since nasopharyngeal pressure
      fluctuates in time, so does the pressure in the middle ear. The effect of these
      pressure changes is to produce a level of ventilation in the middle ear, which
      depends on a combination of three parameters: the volume of the middle ear,
      multiplied by the mean amplitude of pressure variations in the nasopharynx,
      divided by the mean elapsed time between successive eustachian tube openings.
      Assuming steady-state conditions, the composition of middle ear gas can be
      computed and is predicted to range from PN2 = 621, PO2 = 46, PCO2 = 46, PH2O = 47
      mm Hg in the case when nasopharynx fluctuations are small, to a match with
      nasopharyngeal gas composition, when the fluctuations are large.

PMID- 2000020
TI  - Origin of nasal polyps.
AB  - The nasoethmoid complexes from 6 patients with nasal polyps were systematically
      examined. First, the location and place of the origin of the polyps were recorded
      and photographed. The polyps and their places of origin were removed, serial
      sectioned, and examined. In all 6 patients, the polyps originated from the nasal
      mucosa. Most of the polyps extended laterally from the mucosa into the anterior
      part of the middle meatus. Several polyps originated from the mucosa near the
      ethmoid cell ostium or directly from the mucosa lining the edge of the ostium.
      The ostia themselves were not blocked by the polyps, and there was no indication
      of polyp formation in the ethmoid cells.

PMID- 2000021
TI  - Electrophysiologic identification and preservation of the superior laryngeal
      nerve during thyroid surgery.

PMID- 2000022
TI  - Endoscopic transnasal vidian neurectomy.

PMID- 2000023
TI  - The use of heterologous collagen in tympanoplasty.

PMID- 2000025
TI  - Hypertension in obesity may reflect a homeostatic thermogenic response.
AB  - Systemic hypertension of mild to moderate degree is often associated with
      obesity. The hypothesis is that over-eating leads to increased sympathetic
      activity targeted at the peripheral vasculature as well as other tissues in an
      attempt (that in many cases may be futile) to stimulate facultative thermogenesis
      and burn-off the excess energy. This hypothesis represents an important
      modification of one proposed by Landsberg and is supported by: 1) recent
      observations that carbohydrate feeding to humans specifically increases muscle
      sympathetic vasoconstrictor activity in the peroneal nerve, and 2) studies with
      animal models in which active vasoconstriction in the limbs and elsewhere is
      associated with marked increases in oxygen consumption (energy expenditure).

PMID- 2000024
TI  - Target site bioactivation of the neurotoxic organophosphorus insecticide
      parathion in partially hepatectomized rats.
AB  - Target organ bioactivation of phosphorothionate insecticides to their potent
      anticholinesterase oxon metabolites (for example, parathion to paraoxon) may be
      extremely important in toxicity because liver and blood provide so much potential
      protection by a variety of mechanisms, such as the aliesterases which serve as
      alternate phosphorylation sites. To determine whether the brain can produce
      sufficient oxon in vivo to contribute to toxicity, male rats were partially
      hepatectomized and injected i.v. with 1.5 mg/kg parathion. After 30 minutes,
      brain AChE was inhibited 68% whereas liver and plasma aliesterases were
      unaffected. Because aliesterases are far more sensitive to paraoxon inhibition
      than is brain AChE, these results indicate that neither the liver nor extra
      hepatic tissues were contributing oxon into the blood stream. Thus target site
      activation of parathion occurred in vivo at sufficient levels to contribute
      substantially to toxicity.

PMID- 2000026
TI  - Bile secretory characteristics of beta-muricholate and its taurine conjugate are
      similar to those of ursodeoxycholate in the rat.
AB  - Ursodeoxycholate (UDC) has very high biliary transport maxima values (Tm) for its
      conjugates as well as the capability of inducing choleresis rich in bicarbonate
      concentration in the bile in rats. We examined in the present study whether these
      properties are shared by beta-muricholate (beta-MC), using beta-MC, alpha
      muricholate (alpha-MC) and tauro-beta-MC (T beta-MC) in the rat. Bile samples
      were collected every 20 min for 2 hr in male rats under the infusion of alpha- or
      beta-MC (1.2 mumol/min/100g). The choleretic response was quicker in beta-MC
      infused rats than in rats infused with alpha-MC. Bile salt excretion rates
      increased radically in both experiments. However, in beta-MC infused rats, the
      bile salt excretion rate began to decrease after 40 min, whereas in alpha-MC
      infused rats, it continued to increase after 1 hr. Bile bicarbonate concentration
      significantly increased in beta-MC infused rats but not in alpha-MC infused rats.
      The Tm of T beta-MC was 2 times higher than the Tm value for taurocholate and was
      comparable to that of tauroursodeoxycholate (TUDC) which was previously found by
      the authors. The bile flow (Y, microliter/min/100 g) was significantly correlated
      with the bile salt excretion rate (X, mumol/min/100 g) [Y = (6.90 +/- 0.24) X +
      (5.5 + 1.06), n = 41, -0.98, P less than 0.01)], the slope value being higher
      than that found for TUDC. The results suggest that UDC and beta-MC (and their
      conjugates) have very similar bile secretory characteristics and may probably
      share the same transport system in the rat.

PMID- 2000027
TI  - EO-199, a specific antagonist of antiarrhythmic drugs: assessment by binding
      experiments and in vivo studies.
AB  - EO-199, a demethylated analog of the novel class I antiarrhythmic drug EO-122 was
      found to antagonize the antiarrhythmic activity of EO-122 and that of
      procainamide (Class IA). EO-199 did not block significantly the activity of a
      class IB antiarrhythmic agent, lidocaine. EO-199 also displaced the specific
      binding of [3H]EO-122 to rat heart membranes similarly to procainamide whereas
      lidocaine did not. The correlation between binding experiments and
      pharmacological effects points to a possible subclassification of these drugs;
      the two chemical analogs EO-199 and EO-122, as well as procainamide (IA) but not
      lidocaine (IB), compete at the same site or the same state of the sodium channel.
      The availability of a specific antagonist might be useful for studying the
      mechanism of action of antiarrhythmic drugs as well as an antidote in cases of
      antiarrhythmics overdose intoxication.

PMID- 2000028
TI  - Alcohol stimulates Na+/Ca2+ exchange in brain mitochondria.
AB  - Ethanol, at low concentrations, specifically stimulates the Na(+)-dependent
      Ca2(+)-efflux in brain mitochondria. In addition, at higher concentrations,
      ethanol inhibits the Na(+)-independent Ca2(+)-efflux. The electrogenic Ca(+)
      uptake system is not affected by ethanol. The specific stimulation of Na+/Ca2+
      exchange reaches a maximum of 60% stimulation, with half-maximal stimulation at
      130 mM ethanol. The inhibition of the Na(+)-independent efflux is proportional to
      the ethanol concentration, becoming significant only above 200 mM, with 50%
      inhibition at 0.5 M. The inhibition of the Na(+)-independent efflux is, in large
      part, due to an inhibition of the activation of the Cyclosporin-sensitive pore.
      Long-term ethanol-feeding had no effect on the Ca2+ transport systems and their
      sensitivity to acute ethanol treatment. It is suggested that the stimulation of
      the Na(+)-dependent Ca2(+)-efflux, which is the dominant Ca2+ efflux pathway in
      brain mitochondria, contributes to the intoxicating effects of ethanol.

PMID- 2000029
TI  - Protein phosphorylation substrates in normal and neoplastic squamous epithelia of
      the human upper aero-digestive tract.
AB  - Protein phosphorylation was studied in crude and in protein kinase C (Pk-C)
      enriched preparations from squamous cell carcinomas and normal mucosa of the
      human upper aero-digestive tract. In crude soluble preparations from neoplastic
      mucosa we found a 5-fold higher basal endogenous phosphorylation when compared to
      normal mucosa. In particulate fractions the increase was 3-fold. SDS-PAGE and
      autoradiography of phosphorylated proteins in crude soluble tumor extracts showed
      bands corresponding to proteins with apparent molecular weights of 18, 37, 40-42,
      52, 60, 62 and 90 kDa. In normal mucosa the phosphorylation of these proteins was
      very low or absent, except for the proteins with molecular weights of 40-42 and
      52-55 kDa. Addition of Ca2+ or Ca2+/phospholipids to the reaction mixture caused
      phosphorylation of additional proteins with apparent molecular weight of 45-50
      kDa in soluble preparations of tumors. Cyclic AMP or cGMP had no significant
      effect on the phosphorylation of endogenous proteins. In the partially purified,
      Pk-C-enriched fractions the phosphorylation in the presence of Ca2+/phospholipids
      was distinctly higher in tumors when compared to the phosphorylation observed in
      normal mucosa, and some phosphorylation substrates were detected only in tumor
      tissue. In order to find out whether the elevated basal phosphorylation was due
      to an endogenous activation of protein kinases, different inhibitors of
      serine/threonine protein kinases were tested. These inhibitors included: heat
      stable cyclic AMP-dependent protein kinase (Pk-A) inhibitor, Pk-A inhibitor
      peptide (Wiptide), heparin and the Pk-C inhibitors peptide 19-36 and H-7. None of
      these inhibitors had any significant effect on the basal phosphorylation. In
      conclusion, our results show the existence of endogenous phosphorylation
      substrates in human squamous cell carcinomas from the upper aerodigestive tract,
      and indicates that there is a significantly higher basal and Pk-C specific
      phosphorylation of endogenous substrates in tumors compared to normal mucosa.
      This may be of importance for the transformation and altered growth regulation in
      epithelial tumors.

PMID- 2000030
TI  - It works when we all are together--physicians and representatives alike...

PMID- 2000031
TI  - Label reading for health.

PMID- 2000032
TI  - The 1991 Maryland General Assembly: what can we expect?

PMID- 2000033
TI  - Effect of glucose and insulin on triacylglycerol metabolism in isolated normal
      and diabetic skeletal muscle.
AB  - The effects of insulin and glucose on triacylglycerol (TG) metabolism in normal
      and diabetic isolated skeletal muscle were investigated in this study.
      Intracellular TG was continuously synthesized and hydrolyzed in both normal and
      diabetic skeletal muscle. In the absence of insulin and glucose, normal and
      diabetic skeletal muscle TG content and synthesis were decreased. In contrast, in
      the presence of insulin and glucose, the normal and diabetic TG contents were
      unchanged and triacylglycerol synthesis was increased as compared with the
      respective control values. However, insulin and glucose increased intramuscular
      TG content to a greater extent than could be accounted for by their stimulation
      of TG synthesis, indicating that insulin and glucose appear to inhibit TG
      hydrolysis in diabetic muscle, as well as in normal muscle. In addition, these
      data suggest that diabetes causes a defect in the ability of insulin and glucose
      to stimulate TG synthesis, as the increase in diabetic muscle TG synthesis in the
      presence of insulin and glucose was less than in normal muscle.

PMID- 2000034
TI  - Lathosterol level in plasma is elevated in type III hyperlipoproteinemia, but not
      in non-type III subjects with apolipoprotein E2/2 phenotype, nor in type IIa or
      IIb hyperlipoproteinemia.
AB  - We measured the serum lathosterol level, a reflection of the rate of whole body
      cholesterol synthesis, in 15 patients with manifest type III hyperlipoproteinemia
      (HLP), in 20 subjects with apolipoprotein (apo) E2/2 phenotype, but without type
      III HLP, in 21 patients with type IIA and 10 patients with type IIB HLP. A group
      of 100 subjects with apo E3/3 phenotype served as reference. Using ANCOVA,
      lathosterol was adjusted for serum cholesterol and triglyceride concentrations,
      since these parameters were found to independently correlate with lathosterol.
      The adjusted means (+/- SEM), in mumol/L, in these groups were 12.9 +/- 1.1, 8.2
      +/- 1.1, 4.8 +/- 0.9, 9.8 +/- 1.4, and 7.8 +/- 0.4, respectively. Type III HLP
      patients had significantly higher lathosterol levels than all other groups except
      type IIB HLP. In addition, lathosterol was significantly lower in type IIA
      patients than in all other groups. The serum levels of plant sterols, used as a
      reflection of cholesterol absorption, did not differ among the various groups
      after adjustment for serum cholesterol. These findings suggest that an
      overproduction of cholesterol is one factor discriminating E2/2 homozygotes with
      type III HLP from those without the disease.

PMID- 2000035
TI  - Dose-kinetics of pancreatic alpha- and beta-cell responses to a protein meal in
      normal subjects.
AB  - A protein meal is well known to induce a prompt secretion of insulin and
      glucagon. However, the data regarding the dose-response relationship between the
      protein meal and the insulin and glucagon responses are sparse. This study
      assessed the effects of ingestion of protein meals of varying amounts on plasma
      glucose [S], insulin [I], and glucagon [G] concentrations in eight normal
      subjects. Protein meals were administered after an overnight fast in a randomized
      sequence at intervals of 10 days in four different quantities: 250 mg/kg body
      weight (BW) (A), 500 mg/kg BW (B), 1 g/kg BW (C), and 2 g/kg BW (D). Mean S
      levels were not significantly altered following A, B, or C, although significant
      decreases in S responses were noted after C and D as reflected by absolute
      changes (delta) and/or the cumulative responses (CR) and the areas under the
      curve (sigma). Mean I increased promptly to peak concentration by 30 minutes,
      although in individual subjects the peak was achieved either at 30 or 60 minutes
      following all protein meals. The increase was progressively greater and the
      return was delayed with increasing quantities resulting in progressive elevations
      in delta I and percent increase from basal concentration (%), as well as CRI and
      sigma I. G increased following all protein meals as well. The mean peak G
      concentrations were achieved by 90 minutes, although in individual subjects the
      peak G was reached at 90 or 120 minutes, a significant delay in comparison to the
      peak I levels. G returned to base line only following ingestion of A during the
      study period.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2000036
TI  - Comparison of diets supplemented with fish oil or olive oil on plasma
      lipoproteins in insulin-dependent diabetics.
AB  - This study was designed to compare changes in high-density lipoprotein (HDL)- and
      low-density lipoprotein (LDL)-cholesterol in normolipidaemic male insulin
      dependent diabetics (IDD) following dietary supplementation with either the fish
      oil concentrate Max EPA or olive oil. The contribution of the small quantity of
      cholesterol in Max EPA to these changes was also examined. Twenty-seven subjects
      were matched in groups of three and randomly allocated to one of three treatment
      groups of nine subjects each. Subjects were given 15 1-g capsules of oil daily
      for 3 weeks, consisting of either Max EPA, olive oil, or olive oil to which was
      added the same amount of cholesterol as contained in Max EPA, respectively. There
      was a significant increase in eicosapentaenoic acid, and a decrease in
      arachidonic acid, in the platelet membrane phospholipids of subjects taking Max
      EPA. In this group, there was an approximately 30% increase in serum HDL2
      cholesterol (0.59 +/- 0.07 to 0.77 +/- 0.11 mmol/L, mean +/- SEM; P less than
      .01) and a corresponding decrease in HDL3-cholesterol (0.79 +/- 0.03 to 0.71 +/-
      0.03 mmol/L; P less than .05). Although total and LDL-cholesterol concentrations
      were also higher after Max EPA, the changes were not significant. Triglycerides
      were significantly decreased by Max EPA. There were no significant changes in
      lipids in the groups given olive oil. These results show that compared with olive
      oil, dietary supplementation with Max EPA substantially increases HDL2
      cholesterol in insulin-dependent diabetics. This is most likely due to a
      selective effect of omega 3 fatty acids.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2000037
TI  - Influence of sepsis in rats on muscle protein turnover in vivo and in tissue
      incubated under different in vitro conditions.
AB  - We studied the influence of sepsis on muscle protein synthesis and degradation in
      vivo and in muscles, incubated flaccid or at resting length. Sepsis was induced
      in rats by cecal ligation and puncture (CLP). Control rats were sham-operated. A
      flooding dose of 14C-phenylalanine was used to determine muscle protein synthesis
      rate in vivo, and protein breakdown was calculated from the difference between
      protein synthesis and growth rates. Protein synthesis rate in vitro was assessed
      by determining incorporation of 14C-phenylalanine into protein in incubated
      extensor digitorum longus (EDL) and soleus (SOL) muscles. Total and myofibrillar
      protein breakdown rates were determined from release into incubation medium of
      tyrosine and 3-methylhistidine (3-MH), respectively. Muscle protein synthesis
      rate in vivo was reduced by 35%, similar to the reduction observed in muscles
      incubated flaccid or at resting length. The calculated protein breakdown rate in
      vivo was increased by 31% in septic rats. In incubated muscles, the increase in
      total protein breakdown (ie, tyrosine release) during sepsis was almost identical
      in muscles incubated flaccid or at resting length, ie, 83% to 88% in EDL and 47%
      to 49% in SOL. Myofibrillar protein degradation in vitro (ie, 3-MH release) was
      increased approximately 10-fold in EDL muscles incubated flaccid or at resting
      length, but was not significantly affected by sepsis in SOL. Results suggest that
      sepsis-induced changes in protein synthesis observed in muscles incubated either
      flaccid or at resting length reflect changes in vivo. Changes in protein
      breakdown were qualitatively similar in vivo and in vitro, but results in
      incubated muscles may overestimate the increase in muscle proteolysis caused by
      sepsis.

PMID- 2000038
TI  - Hepatic uptake and release of glucose, lactate, and amino acids in acutely uremic
      dogs.
AB  - This study evaluated the potential contribution of the liver to glucose
      intolerance and insulin resistance in acute uremia. Eight bilaterally
      nephrectomized dogs and eight sham-operated dogs were studied, while awake, 24 to
      30 hours after surgery. Blood levels and hepatic balance of glucose, lactate, and
      amino acids were measured during a baseline period and during a 90-minute
      infusion of glucose and insulin that maintained plasma glucose at 9 to 10 mmol/L.
      During the basal state, the acutely uremic dogs, in comparison to control dogs,
      displayed decreased femoral artery plasma glucose, whole blood total amino acids,
      and elevated blood lactate. In the liver of the uremic dogs, there was lower
      glucose output, less uptake of alanine, greater uptake of glutamine, and similar
      uptake of lactate, as compared with controls during the basal state. In the
      control dogs during the hyperglycemic clamp, the liver took up glucose and
      released lactate; the hepatic uptake of alanine diminished, and the hepatic
      output of glutamine persisted. In contrast, during the hyperglycemic clamp in the
      uremic dogs, there was no hepatic uptake of glucose; the hepatic uptake of
      alanine, glutamine, and lactate persisted, and the hepatic uptake of total amino
      acids was greater than in controls. Peripheral glucose uptake was also impaired
      in the acutely uremic dogs. Moreover, the uremic dogs had insulin resistance, as
      indicated by a low ratio of the glucose infusion rate to the plasma insulin
      levels, and a higher urea nitrogen appearance. Thus, acutely uremic dogs have
      altered hepatic handling of glucose and its precursors, which only becomes
      evident during a glucose load.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2000039
TI  - Secretory products from human monocyte-derived macrophages enhance platelet
      aggregation.
AB  - Both macrophages and platelets play an important role in atherogenesis. We
      studied the effect of conditioned medium obtained from human monocyte-derived
      macrophages on in vitro platelet aggregation. Incubation of macrophage
      conditioned medium (MCM) with platelets resulted in enhanced platelet aggregation
      (up to 35% difference between basal and MCM-stimulated activity), which was time
      dependent. This MCM effect on platelet function was increased both with time of
      mononuclear cell culturing (up to 10 days) and with the time of macrophage
      incubation in serum-free medium (up to 24 hours) prior to MCM collection. MCM
      from either cholesterol-loaded macrophages or from macrophages obtained from
      patients with familial hypercholesterolemia demonstrated a 37% and 20% increased
      effect, respectively, in comparison to MCM derived from normal subjects.
      Macrophage activation with lipopolysaccharide resulted in the harvesting of a MCM
      that enhanced platelet activity 60% more than MCM obtained from nonactivated
      cells. The active component of MCM was inhibited fivefold following heating at
      100 degrees C for 10 minutes or after treatment with trypsin or protease, but was
      not affected by antioxidants. MCM activation of blood platelets may be of
      importance in atherogenesis. Understanding the mechanisms involved may contribute
      to an improved appreciation of the role of both platelets and macrophages in
      atherosclerosis.

PMID- 2000040
TI  - Insulin inhibits apolipoprotein B secretion in isolated human hepatocytes.
AB  - The effect of insulin on apolipoprotein (apo) B secretion was investigated in
      human hepatocytes. Freshly isolated hepatocytes, prepared by collagenase
      dispersion of liver specimens, were incubated in serum-free media in the absence
      and presence of 100 nmol/L insulin for 2 hours. The media was then assayed for
      apo B content by radioimmunoassay. In hepatocytes incubated without insulin, the
      secretion of apo B (relative to human low-density lipoprotein [LDL]) was 125 +/-
      37 ng/10(6) cells/2 hours. In the presence of insulin, apo B secretion was
      reduced to 83 +/- 29 ng/10(6) cells/2 hours (34% inhibition, P less than .05).
      These results using human hepatocytes are consistent with previous data from our
      laboratory describing insulin-dependent inhibition of apo B secretion in primary
      cultures of rat hepatocytes and studies by others employing the human-derived
      hepatoma cell line, Hep G2. We conclude that human hepatic apo B secretion is
      under insulin control. The role of more chronic insulin exposure requires further
      investigation.

PMID- 2000041
TI  - Lipogenic potential of liver from morbidly obese patients with and without non
      insulin-dependent diabetes.
AB  - Intra-abdominal liver biopsies were obtained during surgery from fasted obese
      patients with non-insulin-dependent diabetes mellitus (NIDDM), obese
      normoglycemic controls, and lean controls. Lipid synthesis was studied in freshly
      isolated hepatocytes and liver homogenates from the three groups of subjects.
      Incorporation of 3H2O into the lipids of hepatocytes was determined in the
      absence and presence of insulin (0.1 mumol/L). The activities of five enzymes
      involved in fatty acid synthesis, and the incorporation of 14C-glycerol-3
      phosphate into lipids were determined in liver homogenates. Basal lipid synthesis
      by hepatocytes was not different in the three groups of patients. Insulin
      stimulated lipogenesis by 8% +/- 30% in the lean controls, 33% +/- 8% in the
      obese controls and 17% +/- 6% in the NIDDM patients. No significant differences
      in the activities of the five enzymes that are involved in de novo fatty acid
      synthesis among the three groups of patients were observed. Similarly,
      incorporation of 14C-glycerol-3-phosphate by liver homogenates, in the presence
      of saturating or submaximal concentrations of fatty acids, did not differ among
      the three groups. These results show that under the experimental conditions of
      this study, including the fasted state of the patients, the basal capacity of
      liver of NIDDM patients to synthesize fatty acids or glycerides is the same as
      that of liver from obese and lean controls. Thus, it is likely that an increase
      in fatty acid flux into a liver with normal lipogenic potential may contribute to
      the increased synthesis of triglycerides by the liver of these patients in
      vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2000042
TI  - Characterization of a new animal model of chronic hyperprolactinemia.
AB  - Animal models of chronic prolactin (PRL) excess have included rats bearing
      transplantable pituitary tumors that have produced other hypophyseal hormones in
      addition to PRL. We report characterization of a new model, the Buffalo rat
      implanted with the MMQ tumor, a line developed from the 7315a line. Rats
      implanted with the MMQ tumor have serum PRL levels that increase with time and
      correlate with the estimated volume of the subcutaneous tumor. When rats are
      killed 4 weeks after implantation, serum PRL levels are strikingly higher in
      tumor-bearing rats compared with controls (females, 2,723 +/- 266 v 192 +/- 46
      ng/mL, P less than .0001; males, 1,637 +/- 213 v 99 +/- 11 ng/mL, P less than
      .0001). Serum PRL levels measured by the Nb2 lymphoma assay were higher than
      immunoassay measurements in both tumor-bearing and control Buffalo rats. Sephadex
      chromatography of serum from tumor-bearing rats showed that most of the PRL
      immunoreactivity co-eluted with 125I-rPRL. Neither serum growth hormone (GH) nor
      luteinizing hormone (LH) levels were different from controls in tumor-bearing
      rats. Female MMQ-bearing rats had lower estradiol levels. At death, the wet
      weights of adrenal glands, kidneys, and gonads were not affected by the presence
      of tumor. In contrast, tumor-bearing rats had increased spleen weight and
      histological evidence of white pulp hyperplasia. The Buffalo rat implanted with
      the PRL-only MMQ tumor is a promising new tool for the study of chronic
      hyperprolactinemia.

PMID- 2000043
TI  - Dexamethasone-induced increase in the rate of appearance in plasma of gut-derived
      glucose following an oral glucose load in rats.
AB  - Glucocorticoids are known to impair oral glucose tolerance and to induce insulin
      resistance. It has also been reported that glucocorticoids stimulate absorption
      of glucose, water, and electrolytes from the gut. The aim of the present study
      was to determine if dexamethasone treatment increased the rate of appearance in
      plasma of gut-derived glucose. Glucose turnover was measured following an oral
      glucose load in chronically catheterized, nonstressed rats treated for 96 hours
      with either normal saline (n = 14) or dexamethasone (5 micrograms twice daily
      intravenously [IV] (n = 10). Dexamethasone-treated rats had mild glucose
      intolerance and higher insulin levels than control rats. Total glucose turnover
      was increased at all time points following the glucose drink in the dexamethasone
      treated rats, as was the rate of appearance of gut-derived glucose (154 +/- 25 v
      321 +/- 62 mg/45 min; P = .018). It is concluded that in rats, dexamethasone
      treatment increases the rate of appearance in plasma of orally administered
      glucose.

PMID- 2000044
TI  - Myofibrillar proteinase, cathepsin B, and protein breakdown rates in skeletal
      muscle from septic rats.
AB  - Muscle catabolism during sepsis is mainly caused by myofibrillar protein
      breakdown. The mechanism of this metabolic response is not known. We tested the
      hypothesis that increased protein breakdown in the extensor digitorum longus
      (EDL) muscle of septic rats is caused by increased activity of the so-called
      myofibrillar proteinase, which is a nonlysosomal proteolytic enzyme, and
      cathepsin B, which is a lysosomal proteinase. Sepsis, induced in male Sprague
      Dawley rats (50 to 60 g) by cecal ligation and puncture (CLP), resulted in an
      approximately 50% increase in myofibrillar proteinase activity and an
      approximately 30% increase in cathepsin B activity. Concomitantly, both total and
      myofibrillar protein breakdown rates, measured as release of tyrosine and 3
      methylhistidine (3-MH), respectively, by incubated EDL muscles, were
      substantially elevated. Treatment of septic rats with the mast cell degranulating
      compound 48/80 or the lysosomal protease inhibitor leupeptin significantly
      reduced myofibrillar proteinase and cathepsin B activities, but did not affect
      protein breakdown rates. The results suggest that increased protein breakdown in
      septic skeletal muscle is associated with, but not caused by, myofibrillar
      proteinase or cathepsin B activity. The data also support the concept of a mast
      cell origin of the myofibrillar proteinase activity, but do not suggest an
      obligatory involvement of mast cell proteinase in increased protein degradation
      during sepsis.

PMID- 2000045
TI  - Growth hormone improves muscle protein metabolism and whole body nitrogen economy
      in man during a hyponitrogenous diet.
AB  - Healthy male volunteers (n = 12) were given a normocaloric hyponitrogenous diet
      for a conditioning period of 7 days. Thereafter they were blindly randomized to
      receive daily injections of methionyl recombinant human growth hormone (met-hGH)
      0.06 IU/kg or saline during a second week of hyponitrogenous nutrition. The met
      hGH group showed a lower urinary urea excretion and a lower serum concentration
      of urea as compared with the control group. In skeletal muscle, the polyribosome
      concentration, indicative of muscle protein synthesis, as well as the
      concentrations of glutamine, alanine, aspartate, serine, and threonine, decreased
      in the control group, whereas no such changes were seen in the met-hGH-treated
      group. Since provision of met-hGH prevented protein catabolism in muscle and
      improved whole body nitrogen economy, investigations of the possible beneficial
      effects of met-hGH to prevent skeletal muscle vast after surgical trauma are
      advocated.

PMID- 2000046
TI  - Thermogenic synergism between ephedrine and caffeine in healthy volunteers: a
      double-blind, placebo-controlled study.
AB  - Animal and human studies have suggested a thermogenic synergism between ephedrine
      (E), a beta-agonist, and caffeine (C), an adenosine antagonist, which may be
      suitable for the treatment of obesity. To study this phenomenon, the thermogenic
      effect of single doses of oral placebo, E 10 mg, E 20 mg, C 100 mg, and C 200 mg
      were compared with the effects of three different combinations of E + C, 10
      mg/200 mg, 20 mg/100 mg, and 20 mg/200 mg, measured by indirect calorimetry in
      six healthy, lean subjects. The thermogenic effect after E + C 20 mg/200 mg was
      larger than that of any of the other combinations. In this dose ratio, ephedrine
      and caffeine exerted a supra-additive synergism, whereas the thermogenic effects
      of the other two combinations were only additive. The 3-hour postintake increase
      in systolic blood pressure after all three combinations averaged 5 to 7 mm Hg
      more than placebo (P less than .01), which exceeded the predicted additive effect
      fivefold to sevenfold. Diastolic blood pressure was not increased by E + C 20
      mg/200 mg, whereas the other two combinations increased it by approximately 4 mm
      Hg more than placebo. E + C 20 mg/100 mg and 20 mg/200 mg increased heart rate
      more than placebo, while E + C 10 mg/200 mg had no effect on heart rate. As
      expected, all combinations increased plasma glucose, insulin, and C-peptide from
      their ephedrine content. No significant effects of the combinations were found on
      plasma lactate, glycerol, nonesterified fatty acids (NEFA), triglyceride,
      potassium, or sodium.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2000047
TI  - Hypothermia is critical for survival during prolonged insulin-induced
      hypoglycemia in rats.
AB  - Hypothermia is a well-known concomitant of hypoglycemia in mammals. We tested the
      hypothesis that this hypothermia is an important adaptive response to
      hypoglycemia in 11 normal Sprague-Dawley rats. Twelve-hour fasted, conscious
      animals received primed, continuous insulin infusions for up to 8 hours. Plasma
      glucose was clamped between 30 and 40 mg/dL and core body temperature was
      monitored continuously during the insulin infusions. Five of the animals were
      maintained in a room temperature environment (22 to 24 degrees C) during the
      hypoglycemia; all became hypothermic (mean +/- SE nadir core temperature, 31 +/-
      0.5 degrees C). Spontaneous activity was reduced in these animals, but they
      remained conscious and responsive to external stimuli. All five returned to
      normal behavior after euglycemia was restored at the end of the insulin
      infusions. In the remaining six animals, hypothermia was prevented during
      hypoglycemia by warming of the air in their cages (mean of hourly core
      temperatures, 37 +/- 0.1 degrees C). None of these animals survived more than 7
      hours. The severity of the hypoglycemia was no greater in the euthermic than in
      the hypothermic group, as judged by the mean of individual nadir plasma glucose
      levels (25 +/- 1 v 24 +/- 1 mg/dl, respectively) and by the mean number of
      glucose values per animal that were less than 30 mg/dL (2 +/- 1 v 7 +/- 1).
      Plasma osmolality did not change significantly in either group during the period
      of hypoglycemia, suggesting that dehydration was not the cause of death in the
      euthermic animals.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2000048
TI  - Omeprazole and acid peptic disease.

PMID- 2000049
TI  - Pregnancy-induced hypertension: recurrence rate in second pregnancies.
AB  - OBJECTIVE: The purpose of this study was to estimate the rate of recurrence of
      pregnancy-induced hypertension in an Australian population. DESIGN: Case records
      of women with hypertension during pregnancy who were delivered at our hospital
      during a two-year period were examined retrospectively. Those who had pregnancy
      induced hypertension and records of subsequent pregnancies at our hospital were
      examined for recurrence of proteinuric or non-proteinuric pregnancy-induced
      hypertension in their second pregnancy. SETTING: A Sydney teaching hospital with
      approximately 2500 obstetric deliveries per year. PARTICIPANTS: Pregnancy-induced
      hypertension was defined as diastolic blood pressure above 90 mmHg after 20
      weeks' gestation in a nullipara who had normal blood pressure before 16 weeks'
      gestation, with no known history of hypertension or renal disease and whose blood
      pressure returned to normal postpartum. Case records of 610 women were examined;
      236 had records of a second pregnancy at our hospital and of these 140 had
      pregnancy-induced hypertension. MEASUREMENT AND MAIN RESULTS: Of these 140 women
      50% had a normotensive second pregnancy (95% CI, 42%-58%), 47% again developed
      pregnancy-induced hypertension (95% CI, 39%-55%) and 3% (95% CI, 0%-6%) had
      developed chronic, probably essential, hypertension before their second
      pregnancy. Proteinuric pregnancy-induced hypertension occurred in 14% of first
      but only 4.5% of second pregnancies (chi 2(1) = 4.711, df = 1, P less than 0.05).
      CONCLUSIONS: Although these data are limited by retrospective gathering, it is
      clear that there is a high recurrence rate of pregnancy-induced hypertension in
      Australia. However, the risk of having proteinuric pregnancy-induced
      hypertension, a more severe form of this disorder, diminishes in a second
      pregnancy.

PMID- 2000050
TI  - Early blood pressure control improves pregnancy outcome in primigravid women with
      mild hypertension.
AB  - OBJECTIVE AND DESIGN: The aim of this study was to evaluate treatment of mild to
      moderate hypertension (less than 170/110 mmHg) in pregnancy in a prospective,
      randomised, double-blind trial. SETTING AND PATIENTS: Pregnancy outcome was
      studied for 52 primigravid women, managed in hospital from early in the third
      trimester. INTERVENTIONS: Patients were randomly allocated either to placebo or
      to active treatment (clonidine plus hydralazine). MAIN OUTCOME MEASURES AND
      RESULTS: Maternal deterioration dictated withdrawal from trial therapy for eight
      patients receiving placebo, but for only one receiving active treatment. Maternal
      proteinuria occurred only in the placebo group. Intention-to-treat analysis
      showed a significant increase in premature delivery for complications in the
      placebo group (P less than 0.05), despite active blood pressure treatment for
      those withdrawn from the group because of severe hypertension (170/110 mmHg or
      higher). Neonatal respiratory distress requiring intensive care occurred only in
      babies born to women in the placebo group. There were no perinatal deaths and no
      adverse effects of treatment in the neonates. CONCLUSIONS: The study indicates
      that early control of mild hypertension in pregnancy can prevent progression to
      emergency premature delivery.

PMID- 2000051
TI  - The North Coast Cholesterol Check Campaign. Results of the first three years of a
      large-scale public screening programme.
AB  - Although cardiovascular disease (CVD) mortality has been declining, CVD is still
      the major cause of death in Australia and an elevated blood cholesterol level is
      considered a major contributor. Large-scale community-based screening programmes
      in other countries have demonstrated that a population approach can be effective
      in reducing cholesterol levels and the risk of CVD. The North Coast Cholesterol
      Check Campaign is the largest community-based cholesterol intervention programme
      in Australia. Since its inception in 1987, 13% of the Region's adult population
      (over 29,000 persons) have been screened. About half had elevated blood
      cholesterol levels (greater than or equal to 5.5 mmol/L) and were given dietary
      counselling to reduce fat intake. Mean blood cholesterol levels were
      significantly reduced between initial screening and follow-up in all three years.
      Reductions, after correction for regression, were 8%, 6% and 10%, respectively,
      in 1987, 1988 and 1989. There was also a consistent and significant 1.5% to 2%
      reduction in weight. All age/sex cohorts above age 35 were well represented each
      year although self-referral did bias both initial and follow-up samples towards
      women and the aged. Nevertheless, the proportion of men and men in their middle
      age increased during the three years. The proportion of participants with
      elevated cholesterol levels increased in each successive year while the
      proportion of participants who complied with referrals to visit their general
      practitioner and with requests to return for follow-up decreased. Over half of
      the North Coast adult population has now had a cholesterol test. The rate of
      increase in testing since the inception of the Campaign has been approximately
      four times the national rate. North Coast general practitioners have played a
      major role by catering for the increased community demand for cholesterol testing
      and by providing an effective referral service for the Campaign. Community-based
      screening programmes in Australia can detect and beneficially influence large
      numbers of persons with elevated cholesterol levels. Interventions like the North
      Coast Cholesterol Check Campaign, when conducted over a number of years, do
      attract higher risk and less compliant people.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2000052
TI  - Academic general practice in Australian medical schools.
AB  - This paper reports on a survey of the current state of academic general practice
      in the ten Australian medical schools. Despite its lack of resources, low profile
      and ambivalent acceptance in Australian medical schools, academic general
      practice has survived. Its problems and potential contribution for producing
      better doctors are outlined and discussed.

PMID- 2000053
TI  - Current options for the management of gallstones.
AB  - Approximately 20% of the Australian population will develop gallstones. On
      current evidence, patients with asymptomatic gallstones should be treated
      expectantly. Cholecystectomy remains the therapy of choice for patients with
      symptomatic or complicated gallstones. In recent years a number of non-surgical
      treatments have become available for the management of gallstones, the most
      exciting of which is extracorporeal shock wave lithotripsy (ESWL), which is now
      available in Australia. Approximately 20% of patients with symptomatic gallstones
      are suitable for ESWL. Dissolution of gallstones with long-term oral bile acid
      therapy may be appropriate for a small group of patients. Gallstones may also be
      dissolved by the direct application, via a percutaneously placed stent, of the
      dissolving agent, methyl tert-butyl ether; this therapy is currently
      experimental, but it may provide an alternative to surgery in selected patients.

PMID- 2000054
TI  - Chilblains.

PMID- 2000055
TI  - Acupuncture for bronchial asthma? A double-blind crossover study.
AB  - The therapeutic effectiveness of classic Chinese acupuncture was compared with
      "placebo" acupuncture in 15 patients with stable bronchial asthma. The patients
      received treatments with real and placebo acupuncture in a randomly ordered,
      subject and evaluator-blind crossover fashion twice weekly for five weeks. Both
      real and placebo treatment periods were preceded by three week periods when no
      acupuncture was administered. Five patients felt better on real treatment, five
      patients preferred placebo and five did not feel any improvement on either of the
      two treatments. Treatment with real acupuncture when compared with no treatment
      and placebo treatment failed to provide any improvement in daily peak flow rates,
      asthma symptom scores, number of puffs of beta 2-agonist aerosol use, and
      pulmonary function results.

PMID- 2000056
TI  - Cholesterol atheroembolism: an increasingly frequent complication of cardiac
      catheterisation.
AB  - Cholesterol atheroembolisation is increasingly encountered as a complication of
      cardiac catheterisation. We report three cases seen recently in our unit. Autopsy
      and histological evidence confirmed cholesterol atheroembolism in one case, while
      the other two patients presented with classical clinical features of this
      condition. All three patients were elderly with extensive atheromatous disease.
      No excessive difficulty was encountered at catheterisation. Embolisation involved
      the gastrointestinal tract, the skin and extremities, and the kidneys. Despite
      anticoagulation, dialysis and surgical intervention all our patients died. With
      investigative and therapeutic catheterisation being increasingly performed in the
      setting of severe atherosclerosis, the need for continued scrutiny for catheter
      induced complications is emphasised.

PMID- 2000057
TI  - Nodular regenerative hyperplasia of the liver: the importance of combined
      macroscopic and microscopic findings.
AB  - A 40-year-old man with rheumatoid arthritis, splenomegaly and mild
      thrombocytopenia presented with gross ascites and a history of excess alcohol
      consumption. Oesophageal varices were documented endoscopically. Alcoholic
      cirrhosis was suspected and laparoscopy revealed a macronodular liver surface.
      Liver biopsy disclosed subtle microscopic structural variations which together
      with the laparoscopic findings were consistent with the diagnosis of nodular
      regenerative hyperplasia. The importance in diagnosis of macroscopic appearance
      combined with histological findings is emphasised. Clinically significant portal
      hypertension may be present at a histologically early stage of this condition.

PMID- 2000058
TI  - Fourth World suicide and stress.

PMID- 2000059
TI  - Measles immunisation in Australian children.

PMID- 2000060
TI  - The "Nazi doctors" debate.

PMID- 2000061
TI  - Epidural use of methylprednisolone acetate (Depo-Medrol)

PMID- 2000062
TI  - Lung parenchymal laceration: a complication of intercostal catheter insertion.

PMID- 2000063
TI  - Primary lung cancer in Queensland.

PMID- 2000064
TI  - Reference ranges for sodium and potassium.

PMID- 2000066
TI  - Once a patient always a patient.

PMID- 2000065
TI  - Cholesterol-lowering simvastatin achieves listing as a pharmaceutical benefit.

PMID- 2000067
TI  - Sun protection at the cricket.

PMID- 2000069
TI  - Computerised information exchange in health care.

PMID- 2000068
TI  - Childhood ingestion of volatile oils.

PMID- 2000070
TI  - The use of bone mass screening to prevent fractures.

PMID- 2000071
TI  - Are patients clients or people?

PMID- 2000072
TI  - Dog attacks on children.

PMID- 2000073
TI  - Infantile digital entanglement.

PMID- 2000074
TI  - Music therapy in the neonatal intensive care unit.

PMID- 2000075
TI  - Developmental enhancement: implementing a program for the NICU.

PMID- 2000076
TI  - Extend your horizons.

PMID- 2000078
TI  - What to do when the baby turns blue: Part II.

PMID- 2000077
TI  - The Plains Indians: cultural considerations in the use of apnea monitors.

PMID- 2000079
TI  - A nursing retrospective.

PMID- 2000080
TI  - Everything you wanted to know about the National Center for Nursing Research but
      didn't know you should ask.

PMID- 2000081
TI  - Prostaglandin E1.

PMID- 2000082
TI  - Intravenous immunoglobulin therapy in neonatal sepsis.

PMID- 2000083
TI  - A plastome mutation affects processing of both chloroplast and nuclear DNA
      encoded plastid proteins.
AB  - Immunoblotting of a chloroplast mutant (pm7) of Oenothera showed that three
      proteins, cytochrome f and the 23 kDa and 16 kDa subunits of the oxygen-evolving
      subcomplex of photosystem II, were larger than the corresponding mature proteins
      of the wild type and, thus, appear to be improperly processed in pm7. The mutant
      is also chlorotic and has little or no internal membrane development in the
      plastids. The improperly processed proteins, and other proteins that are
      completely missing, represent products of both the plastid and nuclear genomes.
      To test for linkage of these defects, a green revertant of pm7 was isolated from
      cultures in which the mutant plastids were maintained in a nuclear background
      homozygous for the plastome mutator (pm) gene. In this revertant, all proteins
      analyzed co-reverted to the wild-type condition, indicating that a single
      mutation in a plastome gene is responsible for the complex phenotype of pm7.
      These results suggest that the defect in pm7 lies in a gene that affects a
      processing protease encoded in the chloroplast genome.

PMID- 2000084
TI  - Protoplast fusion mediated transfer of oligomycin resistance from Nicotiana
      sylvestris to Solanum tuberosum by intergeneric cybridization.
AB  - We have successfully bridged the intergeneric barriers between Nicotiana and
      Solanum with respect to chondriome transfer. To enable this transfer we utilized
      the donor-recipient protoplast-fusion procedure. Consequently protoplasts of a
      Nicotiana sylvestris line with putatively oligomycin-resistant mitochondria (line
      OliR38) were used as irradiated chondriome donors and iodoacetate-treated
      protoplasts of Solanum tuberosum cv. Desiree served as recipients. The plated
      fusion products as well as their derived colonies and calli were exposed to
      gradually increasing levels of oligomycin. The resulting plantlets had potato
      morphology and were analyzed with respect to their mitochondrial DNA and
      chloroplast DNA. Fifteen out of 50 regenerated plants were verified as true
      cybrids. Detailed analyses of one cybrid revealed chondriome components from the
      oligomycin-resistant donor line, OliR38, but retention of the plastome of potato.
      This cybrid was oligomycin-resistant as revealed by root-culture analysis. It was
      thus verified that due to selection, chondriome components could be transferred
      from a N. sylvestris donor into a cybrid having all the phenotypic features
      controlled by the nucleus of the recipient fusion partner (S. tuberosum).

PMID- 2000085
TI  - Upstream sequences regulating legumin gene expression in heterologous transgenic
      plants.
AB  - We have previously isolated a legumin gene LeB4 from Vicia faba and shown that a
      4.7 kb DNA fragment containing the gene leads to seed-specific expression in
      transgenic tobacco plants. Here we report that the 2.4 kb upstream sequence
      alone, when fused to either the neomycin phosphotransferase II (nptII) gene or
      the beta-glucuronidase (uidA) gene, leads to high enzyme levels in transgenic
      seeds of both tobacco and Arabidopsis. beta-Glucuronidase (GUS) activity is
      especially intense in the cotyledons fading out towards the embryonal root tip, a
      result confirmed by in situ hybridization. Staining of endosperm cells is
      consistent in both species. Analysis of a series of promoter deletion mutants
      fused to the nptII gene and introduced into tobacco plants revealed that about 1
      kb of 5'-flanking sequence is sufficient for high-level expression but indirect
      evidence suggests the presence of weak positive regulatory elements further
      upstream. Deletions leaving only 0.2 kb of upstream sequence reduce enzyme levels
      to less than 10%. A deletion which destroys the legumin box with its seed protein
      gene-specific CATGCATG motif has no obvious effects on expression levels.

PMID- 2000086
TI  - Developmental and environmental regulation of pea legumin genes in transgenic
      tobacco.
AB  - Two distinct legumin genes (LegA1 and LegA2) which encode a major class of seed
      storage protein in pea were isolated from a genomic library. The cloned fragments
      were introduced into tobacco via Agrobacterium-mediated transformation and the
      regenerated plants were used to study the expression characteristics of the genes
      in a heterologous host. It was found that both LegA1 and LegA2 were functional
      members of the pea legumin gene family and that their expression was similar in
      both pea and transgenic tobacco. Legumin was detected only in the seed of tobacco
      where the primary translation products were processed in a manner analogous to
      that which occurs in pea. Legumin gene expression was also shown to be temporally
      regulated during seed development. Legumin polypeptides and mRNA began to
      accumulate 16 days after flowering (DAF), in contrast to the endogenous tobacco
      storage proteins which were apparent at 13 DAF. It was also demonstrated that the
      legumin genes in tobacco were environmentally regulated to the nutritional status
      of the plant. As has been previously shown in pea, legumin accumulation in
      transgenic tobacco seed was progressively reduced when the plants were grown
      under conditions of increasing severity of sulphur-nutrient stress. The reduced
      accumulation of protein was correlated with lower levels of legumin mRNA in the
      developing seed. Despite encoding nearly identical subunits, nucleotide sequence
      data for LegA1 and LegA2 showed that the similarity of their respective 5'
      flanking regions was restricted to several short elements mostly within 240 bp
      from the start of transcription. However, a deletion series using the LegA1 gene
      demonstrated that 237 bp of 5'-flanking sequence was insufficient to permit the
      expression of the legumin gene in tobacco. The data indicated that an as yet
      unidentified sequence element(s) located between positions -668 and -237 was
      essential in re-establishing the high level of regulated gene expression observed
      with the full-length LegA1 gene.

PMID- 2000087
TI  - Analysis of a high frequency transformation system for Ophiostoma ulmi, the
      causal agent of Dutch elm disease.
AB  - A transformation system for Ophiostoma ulmi (Buism.) Nannf. was developed and
      analyzed. Protoplasts were generated from actively budding yeastlike cells by
      digestion with NovoZym 234 in MgSO4 after pretreatment with 2-mercaptoethanol.
      Protoplast regeneration was most efficient when 0.6 M sucrose was used as the
      osmoticum. Several plasmids containing fusions between fungal promoters and a
      bacterial gene for hygromycin phosphotransferase successfully transformed O. ulmi
      to hygromycin resistance. One of these vectors, pPS57, which contains a promoter
      for isopenicillin N synthetase from Penicillium chrysogenum, consistently
      conferred the greatest resistance to hygromycin. Linearization of the vector and
      inclusion of 2-mercaptoethanol in the transformation reaction resulted in
      enhanced transformation efficiency. Approximately 4 x 10(3)
      transformants/micrograms DNA per 10(7) protoplasts were obtained using the
      optimized procedure. Southern hybridization after alternating field and standard
      electrophoresis suggested random insertion of tandem repeats (some greater than
      250 kb) into the fungal chromosomes. Antibiotic resistance was stable through
      mitosis. However, expression of the transforming DNA after meiosis was highly
      variable.

PMID- 2000088
TI  - The sequence-directed bent DNA detected in the replication origin of
      Chlamydomonas reinhardtii chloroplast DNA is important for the replication
      function.
AB  - We demonstrated that the 1055 bp restriction fragment containing OriA, a
      chloroplast DNA replication origin of Chlamydomonas reinhardtii, has
      electrophoretic anomalies characteristic of bent DNA. A tandem dimer of the
      region was constructed. Quantitative measurement of the relative gel mobility of
      a set of permuted fragments was used to extrapolate the approximate position of
      the bent DNA segment. By analyzing the gel mobility of short, sequenced fragments
      of the bent DNA region, the putative bending locus was identified. Two A4 tracts
      and two A5 tracts were located in the bending locus. Oligonucleotide-directed
      mutagenesis was then used to disrupt the A tract or the spacing between A tracts
      and the effect of site-specific mutation on electrophoretic mobility was
      analyzed. To assess the functional role of the bent DNA region, subclones
      containing the bending locus, mutated bending locus, and regions flanking the
      bending locus were constructed. Each subclone was used as template in an in vitro
      DNA replication system which preferentially initiated DNA replication at OriA. A
      224 bp subclone with the bending locus positioned in the middle displayed the
      highest replication function and was sufficient to initiate DNA replication in
      vitro. Site-specific mutations or alterations of the A tracts resulted in
      decreased DNA bending and decreased DNA replication activity.

PMID- 2000089
TI  - In situ hybridization as a rapid means to assess meiotic pairing and detection of
      alien DNA transfers in interphase cells of wide crosses involving wheat and rye.
AB  - The objectives of this study were to determine if biotin-labelled total genomic
      DNA of rye (Secale cereale L.) could be used to (i) preferentially label rye
      meiotic chromosomes in triticale and (ii) detect translocation stocks at
      interphase and/or early prophase by in situ hybridization. Welsh triticale, a
      wheat-rye segmental amphiploid, and Kavkaz wheat, a wheat-rye translocation were
      used. The results indicated that labelled chromosomes of rye and unlabelled
      chromosomes of wheat could be observed throughout all meiotic stages in the
      triticale. For Kavkaz wheat, the presence of the translocated 1RS chromosome arm
      of rye was detected at the interphase or very early prophase stage. Rapid
      assessment of feasibility of gene transfers and detection of alien DNA in somatic
      cells at the interphase stage by in situ hybridization allows for rapid decision
      making and saves time and expense in plant breeding programs.

PMID- 2000090
TI  - The regulatory status of the fixL- and fixJ-like genes in Bradyrhizobium
      japonicum may be different from that in Rhizobium meliloti.
AB  - The cloning, sequencing and mutational analysis of the Bradyrhizobium japonicum
      symbiotic nitrogen fixation genes fixL and fixJ are reported here. The two genes
      were adjacent and probably formed an operon, fixLJ. The predicted FixL and FixJ
      proteins, members of the two-component sensor/regulator family, were homologous
      over almost their entire lengths to the corresponding Rhizobium meliloti proteins
      (approx. 50% identity). Downstream of the B. japonicum fixJ gene was found an
      open reading frame with 138 codons (ORF138) whose product shared 36% homology
      with the N-terminal part of FixJ. Deletion and insertion mutations within fixL
      and fixJ led to a loss of approximately 90% wild-type symbiotic nitrogen fixation
      (Fix) activity, whereas an ORF138 mutant was Fix+. In fixL, fixJ and ORF138
      mutant backgrounds, the aerobic expression of the fixR-nifA operon was not
      affected. NifA itself did not regulate the expression of the fixJ gene. Thus, the
      B. japonicum FixL and FixJ proteins were neither involved in the regulation of
      aerobic nifA gene expression nor in the anaerobic NifA-dependent autoregulation
      of the fixRnifA operon, rather they appeared to control symbiotically important
      genes other than those whose expression was dependent on the NifA protein. The
      fixL and fixJ mutant strains were unable to grow anaerobically with nitrate as
      the terminal electron acceptor. Therefore, some of the FixJ-dependent genes in B.
      japonicum may be concerned with anaerobic respiration.

PMID- 2000091
TI  - Cell-specific accumulation of maize phosphoenolpyruvate carboxylase is correlated
      with demethylation at a specific site greater than 3 kb upstream of the gene.
AB  - Development of the C4 photosynthetic pathway relies upon the cell-specific
      accumulation of photosynthetic enzymes. Although the molecular basis of this cell
      specific gene expression is not known, regulation appears to be exerted at the
      level of transcript accumulation. We have investigated the relationship between
      gene expression patterns and DNA methylation for genes of two of the C4
      photosynthetic enzymes, ribulose bisphosphate carboxylase (RuBPCase) and
      phosphoenolpyruvate carboxylase (PEPCase). We found no correlation between
      methylation state and gene expression for either the large subunit or a small
      subunit gene of RuBPCase. In contrast, demethylation of a specific site 5' to the
      PEPCase gene was correlated with the light-induced, cell-specific accumulation of
      PEPCase mRNA. This differentially methylated site is positioned at great distance
      (greater than 3 kb) from the start of transcription. This observation is made
      more interesting by the fact that the immediate 5' region of the gene, and some
      of the coding region, represents an unmethylated CpG island. Such islands are
      normally associated with constitutively expressed genes.

PMID- 2000092
TI  - Structural and functional analysis of promoter from gliadin, an endosperm
      specific storage protein gene of Triticum aestivum L.
AB  - To identify cis-regulatory elements of the gliadin gene, a study of the gliadin
      gene promoter was conducted by transient expression analysis of plasmid DNAs
      which were introduced into plant protoplasts by electroporation. The promoter
      region (-592 bp to +18 bp from the translational start) of this developmentally
      regulated gene, when fused upstream to the chloramphenicol acetyl transferase
      (CAT) reporter cassette was unable to direct significant CAT expression in wheat
      or tobacco suspension cells. Because this monocot gene promoter appeared to be
      under stringent tissue-specific control, a hybrid promoter approach using a
      nopaline synthase (nos) promoter was employed. A series of 3' deletions of the
      gliadin promoter were placed upstream of either a nonfunctional -101 nos or a
      nearly wild-type -155 nos promoter fused in turn to a CAT reporter gene cassette.
      Transient expression analysis of these plasmid DNAs in tobacco cells showed that
      the gliadin fragment could either restore the activity of the non-functional nos
      promoter (series I) or enhance the activity of the functional nos promoter
      (series II). The degree of restoration of the promoter function conferred by
      gliadin fragments of the first series was proportional to the enhancing effect of
      the same fragments in the second series of constructs. The transcriptional
      activity of the gliadin (-592 bp to -77 bp) -nos hybrid promoter was reduced by
      26% upon 3' deletion of sequences in the region -141 bp to -77 bp, which contains
      both the TATA and CCAAT boxes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2000093
TI  - Nuclear tRNA(Tyr) genes are highly amplified at a single chromosomal site in the
      genome of Arabidopsis thaliana.
AB  - We have examined the organization of tRNA(Tyr) genes in three ecotypes of
      Arabidopsis thaliana, a plant with an extremely small genome of 7 x 10(7) bp.
      Three tRNA(Tyr) gene-containing EcoRI fragments of 1.5 kb and four fragments of
      0.6, 1.7, 2.5 and 3.7 kb were cloned from A. thaliana cv. Columbia (Col-O) DNA
      and sequenced. All EcoRI fragments except those of 0.6 and 2.5 kb comprise an
      identical arrangement of two tRNA(Tyr) genes flanked by a tRNA(Ser) gene. The
      three tRNA genes have the same polarity and are separated by 250 and 370 bp,
      respectively. The tRNA(Tyr) genes encode the known cytoplasmic tRNA(G psi ATyr).
      Both genes contain a 12 bp long intervening sequence. Densitometric evaluation of
      the genomic blot reveals the presence of at least 20 copies, including a few
      multimers, of the 1.5 kb fragment in Col-O DNA, indicating a multiple
      amplification of this unit. Southern blots of EcoRI-digested DNA from the other
      two ecotypes, cv. Landsberg (La-O) and cv. Niederzenz (Nd-O) also show 1.5 kb
      units as the major hybridizing bands. Several lines of evidence support the idea
      of a strict tandem arrangement of this 1.5 kb unit: (i) Sequence analysis of the
      EcoRI inserts of 2.5 and 0.6 kb reveals the loss of an EcoRI site between 1.5 kb
      units and the introduction of a new EcoRI site in a 1.5 kb dimer. (ii) Complete
      digestion of Col-O DNA with restriction enzymes which cleave only once within the
      1.5 kb unit also produces predominantly 1.5 kb fragments. (iii) Partial digestion
      with EcoRI shows that the 1.5 kb fragments indeed arise from the regular spacing
      of the restriction sites.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2000094
TI  - Intron enhancement of gene expression and the splicing efficiency of introns in
      maize cells.
AB  - The inclusion of the alcohol dehydrogenase 1-S(Adh 1-S) intron 1 in the
      transcription unit of maize gene constructs has been shown to increase gene
      expression in cultured maize cells. We have extended these studies with Adh1-S
      intron 1 using the firefly luciferase, Escherichia coli beta-glucuronidase and
      chloramphenicol acetyltransferase reporter genes adjoined to different plant
      promoters and find enhancement of transient gene expression in all cases but one.
      We also show that the enhancement phenomenon can be mediated by the third intron
      of the maize actin gene. In all cases tested, the inclusion of an intron results
      in increased levels of steady-state RNA. The degree of enhancement depends on the
      exon sequences flanking the intron; flanking exons also influence the efficiency
      of intron splicing. Unexpectedly, unspliced RNAs accumulate during the transient
      assay.

PMID- 2000095
TI  - Induction of specific-locus mutations in male germ cells of the mouse by
      acrylamide monomer.
AB  - Acrylamide monomer (AA), injected into male mice at the maximum tolerated dose of
      5 x 50 mg/kg (24-h intervals), significantly increased the specific-locus
      mutation rate in certain poststem-cell stages of spermatogenesis, but not in
      spermatogonial stem cells. Germ-cell stages in which the treatment induced
      dominant lethals--namely, exposed spermatozoa and late spermatids (number of
      surviving offspring only 3% and 27%, respectively, of those in concurrent
      controls)--jointly yielded the highest frequency of specific-locus mutations. AA
      thus conforms to Pattern 1 in our earlier classification of chemicals according
      to the spermatogenic stage at which they elicit maximum response (Russell et al.,
      1990). No specific-locus mutations were observed among 17,112 offspring derived
      from exposed spermatogonial stem cells, a result which rules out (at the 5%
      significance level) an induced mutation rate greater than 2.3 times the
      historical control rate. A sustained high productivity in matings made for
      several months following week 3 indicates that there is no significant
      spermatogonial killing and that cell selection is presumably not the explanation
      for the negative result. On the basis of genetic and/or cytogenetic evidence, the
      mutations induced postmeiotically by AA were 'large lesions' (multi-locus), while
      one of 2 recovered from exposure of differentiating spermatogonia is probably a
      small lesion. An earlier survey of mammalian mutagenesis results led us to
      conclude that, regardless of the classification of a chemical according to the
      stage at which it elicits its maximum response, the nature of mutations is
      determined by the germ-cell stage in which they are induced (Russell et al.,
      1990). The AA results on lesion size and on distribution of mutations among the
      loci fit the general pattern.

PMID- 2000096
TI  - Uric acid as an inhibitor of cyclophosphamide-induced micronuclei in mice.
AB  - Swiss albino male mice, 6-8 weeks old, were treated orally with different doses
      of uric acid dissolved in water for 7 days. Some of the mice in each group were
      injected i.p. with cyclophosphamide (25 mg/kg) and killed after 30 h. The blood
      of all animals was analyzed for uric acid levels. The femoral cells of the mice
      in different groups were collected and studied. Uric acid was found to be devoid
      of mitodepressant or clastogenic activity at 10-100 mg/kg/day. Pretreatment with
      uric acid was found to provide significant protection against cyclophosphamide
      induced bone marrow depression and micronucleated polychromatic erythrocytes.

PMID- 2000097
TI  - A genetic study of human interferon-alpha-induced repair of DNA damage in
      hepatitis B patients.
AB  - In vitro treatment with human interferon-alpha (HuIFN-alpha) of hepatitis B virus
      infected peripheral lymphocytes from 17 hepatitis B patients induced a decrease
      in the frequency of sister-chromatid exchanges (SCE). There was a significant
      difference in mean SCE frequencies between the HuIFN-alpha-treated patients and
      the control group, but not between acute and chronic hepatitis B patients treated
      with HuIFN-alpha.

PMID- 2000098
TI  - Starvation as an inducer of error-free DNA repair in Escherichia coli.
AB  - Previous work in this laboratory has shown that heat shock or vitamin B1
      deprivation induces an error-free DNA-repair process in Escherichia coli. The
      system is absolutely dependent on excision repair, while its induction is delayed
      in lon- or recA- cells. We have now shown that starvation of E. coli for amino
      acids, glucose or phosphate, conditions known to induce the stringent response or
      the glu and pho regulons, respectively, leads to a similar uvrA-dependent
      increase in UV resistance and decrease in UV-induced mutation frequency. These
      results support the hypothesis that the effect is a general response to non
      mutagenic stress that may play an important role in the survival of cells exposed
      to harsh environments.

PMID- 2000099
TI  - In vitro genotoxicity of dimethyl terephthalate.
AB  - Dimethyl terephthalate (DMTP), the para configuration of dimethyl phthalate, is
      one of the basic monomers used in the synthesis of polyethylene terephthalate
      (PET) plastics. Human exposure to DMTP may primarily occur during the manufacture
      of PET fibers and films. The mutagenic potential of dimethyl terephthalate was
      evaluated using a battery of in vitro short-term tests: the Ames test; DNA single
      strand break assays in CO60 cells and in primary rat hepatocytes; UDS in HeLa
      cells; chromosome aberration and micronucleus assays in human peripheral blood
      lymphocytes; selective DNA amplification in CO60 and in Syrian hamster embryo
      cells. The results of this battery of in vitro assays clearly show that DMTP is
      nongenotoxic. By contrast, other authors have found DMTP to be an in vivo
      clastogenic compound and suggested that the mechanisms involved in these in vivo
      effects seem to have nothing in common with genotoxicity and are still unknown.

PMID- 2000100
TI  - Effects of selenium deficiency on sperm morphology and spermatocyte chromosomes
      in mice.
AB  - Sperm morphology and spermatocyte chromosomes were examined in mice maintained on
      a Torula yeast diet for 5 weeks. In the selenium-deficient group, the proportion
      of abnormal sperm was high, ranging from 6.8% to 49.6%, while in the control
      group it ranged from only 4.0% to 15.0%. The most frequently occurring
      abnormalities in sperm shape were in the sperm head. There was also a tendency
      for abnormalities in other regions (neck, midpiece and tail) to be increased.
      However, in metaphase-I spermatocytes, the frequencies of various types of
      abnormal chromosomes (univalent chromosomes, translocations and structural
      anomalies) did not differ between the selenium-deficient and control groups.
      These findings indicate that selenium day be an essential constituent for
      spermatogenesis in mice.

PMID- 2000101
TI  - Recording characteristics of monopolar EMG electrodes.
AB  - Motor unit action potentials (MUAPs) and the electromyographic (EMG) interference
      pattern (IP) were recorded from the biceps muscle of 5 normal subjects using both
      a concentric needle (CN) and a disposable monopolar needle (MN) electrode. The
      MUAPs recorded by the MN electrode had higher amplitude and area and were more
      frequently complex than those recorded with the CN electrode. The MUAP duration
      and area: amplitude ratio were similar for both electrodes. Although the MN
      electrode had a larger recording surface, its dimensions (maximum diameter and
      length of the cone shaped tip) were similar to those of the CN electrode (minor
      and major axes of the elliptical recording tip). Based on these observations, we
      infer that the MN electrode may be more selective than the CN electrode, ie, the
      AP amplitude recorded by the MN electrode decreases faster than the AP amplitude
      recorded by a CN electrode when the distance of the muscle fiber from the
      recording electrode increases. Photomicrographs of the MN electrode after use
      demonstrated no evidence that the insulating material had peeled off. There was
      also no evidence that MUAP measurement values changed during the recordings as
      would be expected if the recording surface changed due to peeling of the
      insulating material.

PMID- 2000102
TI  - Inhibition of motoneuron discharge by peripheral nerve stimulation: an F response
      analysis.
AB  - F waves were recorded from the abductor pollicis brevis stimulating the median
      nerve at the wrist. These data were compared to responses obtained after
      preceding supramaximal stimulation of digital fibers of the second (II) finger or
      the median nerve at the wrist. The time between conditioning and test stimuli
      were 50 msec. Following conditioning stimuli, F wave latencies were significantly
      increased while F amplitudes, durations, and persistences were all decreased.
      Chronodispersion was not significantly affected. These changes were associated
      with increased repetition of individual F responses. The most prominent changes
      were found after stimulation of fibers of digit II but only at levels of
      stimulation supramaximal for the sensory nerve action potential. Some, but
      relatively limited, changes were present after stimulation of digital fibers of
      the fifth finger. The results are consistent with afferent fiber, probably A
      delta, inhibition of antidromic motoneuron activation with associated decrease in
      central motor neuron pool excitability. The study also demonstrates that, except
      for chronodispersion, changes in F waves found with peripheral nerve injury may
      also occur due to physiological changes in the central nervous system.

PMID- 2000103
TI  - Synchronous positive and negative myoclonus due to pontine hemorrhage.
AB  - We report a case of synchronous positive and negative myoclonus following pontine
      hemorrhage. Constant synchronous jerking of the eyes, tongue, face, mandible,
      larynx, pharynx, and diaphragms persisted during sleep. Jerking of limb muscles
      occurred during volitional activities, but not at rest. Inability to sustain
      glottic adduction during phonation contributed to severe dysarthria.
      Electromyography (EMG) revealed positive myoclonus of the branchial musculature
      with synchronous negative myoclonus in a generalized distribution. Treatment with
      trazodone reduced the ocular myoclonus but worsened the dysphagia. We suggest
      that a single neural rhythm generator may produce both positive and negative
      myoclonus.

PMID- 2000104
TI  - Uni- and bipolar surface recording of human nerve responses.
AB  - Nerve conduction studies are of great clinical value in diagnosing nerve
      pathology and injury. In most neurophysiological laboratories nerve conduction
      recordings are routinely made with surface bipolar electrodes. More rarely,
      needle electrodes are used. A bipolarly recorded nerve action potential (NAP) is
      the difference between 2 unipolar NAPs recorded from each pole of a bipolar
      electrode and a remote reference. The delay between the 2 separated unipolar NAPs
      depends on the distance between the poles and the conduction velocity (CV). When
      the delay between the unipolar NAPs was increased (partly through simulation),
      the following changes of the bipolar NAP occurred: (1) total amplitude was
      maximal at a certain delay but decreased if the delay was shorter or longer, (2)
      latencies of the first positive and the first negative peaks increased slightly
      until their amplitudes reached maximal values, (3) a second negative peak of
      increasing latency appeared with longer delays, (4) latencies of later peaks
      increased linearly, and (5) total area increased nonlinearly. All parameters of
      the bipolarly recorded NAP (except the onset of the first positive phase) changed
      with increasing delay. The significance of this is that if NAPs are recorded with
      a bipolar electrode, standard values obtained for each nerve cannot be
      transferred between laboratories if different interelectrode (interpolar)
      distances are used. Furthermore, the assumption that a fixed interelectrode
      distance allows comparisons between reference values and patient data is
      incorrect.

PMID- 2000105
TI  - Segregation by modality of myelinated and unmyelinated fibers in human sensory
      nerve fascicles.
AB  - Thin diameter concentric needle electrodes with a small recording surface were
      used to explore the characteristics of neighboring fibers in sensory median nerve
      fascicles. Fibers which were close neighbors in the fascicle, were not randomly
      distributed intraneurally. Instead there was an intrafascicular segregation by
      modality of both myelinated and unmyelinated fibers. In addition, evidence was
      obtained which suggested that the contents of different Schwann cells vary. Some
      Schwann cell systems envelop afferent C fibers whereas others hold efferent
      sympathetic C axons. The results imply a modality segregation amongst both A and
      C fibers in human peripheral sensory nerve fascicles.

PMID- 2000106
TI  - Dystrophin expression in myotubes formed by the fusion of normal and dystrophic
      myoblasts.
AB  - Mdx mouse dystrophy is characterized by the absence in the muscle cytoplasmic
      membrane of a high molecular weight protein called dystrophin. A possible avenue
      for treatment of muscular dystrophies is to inject normal myoblasts in a
      dystrophic muscle to form hybrid muscle fibers. Hybrid myotubes were formed in
      vitro by the fusion of normal rat and dystrophic mouse (mdx) myoblasts. Staining
      with Hoechst dye 33258 permitted the clear distinction of mouse and rat nuclei.
      Immunostaining demonstrated that dystrophin was present over the entire membrane
      of all hybrid myotubes even when nuclei ratio normal/dystrophic was low.

PMID- 2000107
TI  - Diagnostic yield of different electrophysiological methods in carpal tunnel
      syndrome.

PMID- 2000108
TI  - AAEM case report #1: ulnar neuropathy at the elbow.
AB  - A patient with bilateral cubital syndrome complicated by anomalous innervation is
      presented. The electrodiagnostic approach to patients with this neuropathy is
      reviewed emphasizing new developments. The interpretation of the findings in this
      patient centers around issues of pathophysiology and methodology.

PMID- 2000109
TI  - A comparison of surfactant as immediate prophylaxis and as rescue therapy in
      newborns of less than 30 weeks' gestation.
AB  - BACKGROUND: Exogenous pulmonary surfactants are administered into the trachea
      either to prevent respiratory distress syndrome in premature infants or to treat
      it. In a randomized, multicenter trial, we compared the results of surfactant
      therapy initiated as prophylaxis with the results of rescue therapy with
      surfactant. METHODS: Before birth, 479 infants with an estimated gestational age
      of less than 30 weeks were randomly assigned to receive surfactant as prophylaxis
      (n = 235) or rescue therapy (n = 244). The infants in the prophylaxis group
      received a 90-mg intratracheal dose of an exogenous calf-lung surfactant extract
      at the time of delivery, whereas the infants in the rescue-therapy group received
      90 mg of the surfactant several hours after delivery if the fractional
      inspiratory oxygen concentration was at least 0.40 or if the mean airway pressure
      was at least 0.686 kPa (7 cm of water), or both. Infants in both groups received
      additional doses of surfactant at intervals of 12 to 24 hours if these criteria
      were met. RESULTS: The proportion of infants surviving until discharge to their
      homes was significantly higher in the prophylaxis group than in the rescue
      therapy group (88 vs. 80 percent, P = 0.028). This difference was due primarily
      to the longer survival of very premature infants (less than or equal to 26 weeks'
      gestation) in the prophylaxis group than in the rescue-therapy group (75 vs. 54
      percent, P = 0.006). According to proportional-hazards regression analysis, the
      distribution of survival times was better for all infants in the prophylaxis
      group (P = 0.007) and for the subgroup of infants in the prophylaxis group who
      were delivered at 26 weeks' gestation or earlier (P = 0.0048). Infants in the
      prophylaxis group who were delivered at 26 weeks' gestation or earlier had a
      lower incidence of pneumothorax than similar infants in the rescue-therapy group
      (7 vs. 18 percent, P = 0.03). CONCLUSIONS: We found a significant advantage to
      the administration of the initial dose of surfactant as prophylaxis rather than
      as rescue therapy in very premature infants.

PMID- 2000110
TI  - A prospective study of advance directives for life-sustaining care.
AB  - BACKGROUND: The use of advance directives is recommended so that people can
      determine the medical care they will receive when they are no longer competent,
      but the effectiveness of such directives is not clear. METHODS: In a prospective
      study conducted over a two-year period, 126 competent residents of a nursing home
      and 49 family members of incompetent patients were interviewed to determine their
      preferences with respect to hospitalization, intensive care, cardiopulmonary
      resuscitation, artificial ventilation, surgery, and tube feeding in the event of
      critical illness, terminal illness, or permanent unconsciousness. Advance
      directives, consisting of signed statements of treatment preferences, were placed
      in the medical record to assist in care in the nursing home and to be forwarded
      to the hospital if necessary. RESULTS: In an analysis of 96 outcome events
      (hospitalization or death in the nursing home), care was consistent with
      previously expressed wishes 75 percent of the time; however, the presence of the
      written advance directive in the medical record did not facilitate consistency.
      Among the 24 events in which inconsistencies occurred, care was provided more
      aggressively than had been requested in 6 cases, largely because of unanticipated
      surgery or artificial ventilation, and less aggressively than requested in 18,
      largely because hospitalization or cardiopulmonary resuscitation was withheld.
      Inconsistencies were more likely in the nursing home than in the hospital.
      CONCLUSIONS. The effectiveness of written advance directives is limited by
      inattention to them and by decisions to place priority on considerations other
      than the patient's autonomy. Since our study was performed in only one nursing
      home and one hospital, other studies are necessary to determine the
      generalizability of our findings.

PMID- 2000111
TI  - Advance directives for medical care--a case for greater use.
AB  - BACKGROUND. Advance directives for medical care and the designation of proxy
      decision makers to guide medical care after a patient has become incompetent have
      been widely advocated but little studied. We investigated the attitudes of
      patients toward planning, perceived barriers to such planning, treatment
      preferences in four hypothetical scenarios, and the feasibility of using a
      particular document (the Medical Directive) in the outpatient setting to specify
      advance directives. METHODS: We surveyed 405 outpatients of 30 primary care
      physicians at Massachusetts General Hospital and 102 members of the general
      public in Boston and asked them as part of the survey to complete the Medical
      Directive. RESULTS: Advance directives were desired by 93 percent of the
      outpatients and 89 percent of the members of the general public (P greater than
      0.2). Both the young and the healthy subgroups expressed at least as much
      interest in planning as those older than 65 and those in fair-to-poor health. Of
      the perceived barriers to issuing advance directives, the lack of physician
      initiative was among the most frequently mentioned, and the disturbing nature of
      the topic was among the least. The outpatients refused life-sustaining treatments
      in 71 percent of their responses to options in the four scenarios (coma with
      chance of recovery, 57 percent; persistent vegetative state, 85 percent;
      dementia, 79 percent; and dementia with a terminal illness, 87 percent), with
      small differences between widely differing types of treatments. Specific
      treatment preferences could not be usefully predicted according to age, self
      rated state of health, or other demographic features. Completing the Medical
      Directive took a median of 14 minutes. CONCLUSIONS: When people are asked to
      imagine themselves incompetent with a poor prognosis, they decide against life
      sustaining treatments about 70 percent of the time. Health, age, or other
      demographic features cannot be used, however, to predict specific preferences.
      Advance directives as part of a comprehensive approach such as that provided by
      the Medical Directive are desired by most people, require physician initiative,
      and can be achieved during a regular office visit.

PMID- 2000112
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 13-1991. A 63-year-old woman with coronary-artery disease, a
      pulmonary infiltrate, and sudden death.

PMID- 2000113
TI  - Surfactant-replacement therapy.

PMID- 2000114
TI  - Cholesterol intake and serum cholesterol level.

PMID- 2000115
TI  - The Marlboro Grand Prix. Circumvention of the television ban on tobacco
      advertising.

PMID- 2000116
TI  - The influence of the U.S. tobacco industry on the health, economy, and
      environment of developing countries.

PMID- 2000117
TI  - Reforming the health care system.

PMID- 2000118
TI  - Beta carotene to prevent skin cancer.

PMID- 2000119
TI  - Correction: Hereditary cutaneous malignant melanoma-dysplastic nevus.

PMID- 2000120
TI  - Special hospitals for patients with HIV infection.

PMID- 2000121
TI  - Chloroquine-resistant Plasmodium vivax from Indonesia.

PMID- 2000122
TI  - Auditory vestibular dysfunction after high-impact aerobics.

PMID- 2000124
TI  - More spending, not more of the same.

PMID- 2000123
TI  - Bowling plexopathy.

PMID- 2000125
TI  - Another tough year for MRC.

PMID- 2000126
TI  - Cancer therapy. Neutron-treatment fund axed.

PMID- 2000127
TI  - Antarctic research. French research threatened.

PMID- 2000128
TI  - Man's inhumanity.

PMID- 2000129
TI  - Neurobiology. Nematodes in nervous decline.

PMID- 2000130
TI  - Synthetic chemistry. A radical approach to cancer.

PMID- 2000131
TI  - Sodium-calcium exchange. Ins and outs of Ca2+ transport.

PMID- 2000132
TI  - AIDS. Of mice, monkeys and men.

PMID- 2000133
TI  - Spongiform encephalopathies. The prion's progress.

PMID- 2000134
TI  - Risks of handling HIV.

PMID- 2000135
TI  - Molecular operations of the sodium-calcium exchanger revealed by conformation
      currents.
AB  - The sodium-calcium exchanger is critical in the normal functioning of many cells.
      In heart muscle, it is the principal way by which the cells keep the
      concentration of intracellular calcium low, pumping out the Ca2+ that enters the
      cytosol through L-type Ca2+ channels. The exchanger may also contribute to the
      triggering of Ca2+ release during voltage-activated excitation-contraction
      coupling in heart. Time resolved examination of the conformational changes of
      macromolecules in living cells has so far been largely restricted to ion-channel
      proteins whose gating is voltage-dependent. We have now directly measured
      electrical currents arising from the molecular rearrangements of the sarcolemmal
      Na-Ca exchanger. Changes in the conformation of the exchanger protein were
      activated by a rapid increase in the intracellular calcium concentration produced
      by flash photolysis of caged calcium in voltage-clamped heart cells. Two
      components of membrane current were produced, reflecting a calcium-dependent
      conformational change of the transporter proteins and net transport of ions by
      the exchanger. The properties of these components provide evidence that the Na-Ca
      exchanger protein undergoes two consecutive membrane-crossing molecular
      transitions that each move charge, and that there are at least 250 exchangers per
      micron 2 turning over up to 2,500 times per second.

PMID- 2000136
TI  - A homologue of the bacterial heat-shock gene DnaJ that alters protein sorting in
      yeast.
AB  - Heat-shock proteins have been implicated in assembly of protein complexes,
      correct protein folding and uptake of proteins into organelles. In Escherichia
      coli, the heat-shock protein DnaJ and the Hsp70 homologue, DnaK, act together to
      disassemble a protein complex involved in bacteriophage lambda replication. We
      report the identification of SCJ1, a gene in the yeast Saccharomyces cerevisiae
      that encodes a homologue of the bacterial DnaJ protein. SCJ1 was identified by a
      genetic screen in which increased expression of candidate genes results in
      missorting of a nuclear-targeted test protein. The predicted amino-acid sequence
      of SCJ1 is 37% identical to the entire E. coli DnaJ protein. Hybridization
      experiments indicate that there is a family of yeast genes related to SCJ1. These
      findings suggest that the Hsp70 DnaK-DnaJ interaction is general to eukaryotes.

PMID- 2000137
TI  - Complex patterns formed by motile cells of Escherichia coli.
AB  - When chemotactic strains of the bacterium Escherichia coli are inoculated on semi
      solid agar containing mixtures of amino acids or sugars, the cells swarm outwards
      in a series of concentric rings: they respond to spatial gradients of attractants
      generated by uptake and catabolism. Cells also drift up gradients generated
      artificially, for example by diffusion from the tip of a capillary tube or by
      mixing. Here we describe conditions under which cells aggregate in response to
      gradients of attractant which they excrete themselves. When cells are grown in
      semi-solid agar on intermediates of the tricarboxylic acid cycle, they form
      symmetrical arrays of spots or stripes that arise sequentially. When cells in a
      thin layer of liquid culture are exposed to these compounds, spots appear
      synchronously, more randomly arrayed. In either case, the patterns are
      stationary. The attractant is a chemical sensed by the aspartate receptor. Its
      excretion can be triggered by oxidative stress. As oxygen is limiting at high
      cell densities, aggregation might serve as a mechanism for collective defence.

PMID- 2000138
TI  - Demonstration by NMR of folding domains in lysozyme.
AB  - Although there has been much speculation on the pathways of protein folding, only
      recently have experimental data on the topic been available. The study of
      proteins under conditions where species intermediate between the fully folded and
      unfolded states are stable has provided important information, for example about
      the disulphide intermediates in BPTI, cis/trans proline isomers of RNase A3 and
      the molten globule state of alpha-lactalbumin. An alternative approach to
      investigating folding pathways has involved detection and characterization of
      transient conformers in refolding studies using stopped-flow methods coupled with
      NMR measurements of hydrogen exchange. The formation of intermediate structures
      has been detected in the early stages of folding of cytochrome c, RNaseA and
      barnase. For alpha-lactalbumin, hydrogen exchange kinetics monitored by NMR
      proved to be crucial for identifying native-like structural features in the
      stable molten globule state. An analogous partially folded protein stable under
      equilibrium conditions has not been observed for the structurally homologous
      protein hen egg-white lysozyme, although there is evidence that a similar but
      transient state is formed during refolding. Here we describe NMR experiments
      based on competition between hydrogen exchange and the refolding process which
      not only support the existence of such a transient species for lysozyme, but
      enable its structural characteristics to be defined. The results indicate that
      the two structural domains of lysozyme are distinct folding domains, in that they
      differ significantly in the extent to which compact, probably native-like,
      structure is present in the early stages of folding.

PMID- 2000139
TI  - Biotechnology of age.

PMID- 2000140
TI  - Cancer epidemiology. Gold mine in east Germany.

PMID- 2000141
TI  - Biotechnology. Staying in competition.

PMID- 2000142
TI  - Fluoride given the all clear.

PMID- 2000143
TI  - New twist in the long saga of HIV.

PMID- 2000144
TI  - Human genetics. Methylation and the fragile X.

PMID- 2000145
TI  - Sequence analysis of original HIV-1.

PMID- 2000146
TI  - Signalling and superinduction.

PMID- 2000147
TI  - Ancient HLA genes from 7,500-year-old archaeological remains.
AB  - In the past decade there has been increasing interest in cloning DNA from ancient
      and preserved tissues. Most studies, however, have focused on mitochondrial or
      chloroplast genes, present at hundreds to thousands of copies per cell compared
      with one or two for each nuclear gene. With a probe containing Alu repeat
      sequences, Paabo isolated a 3.4-kilobase DNA fragment from a 2,400-year-old
      Egyptian mummy which was subsequently shown to contain an intron of the nuclear
      gene HLA-DQA (ref. 11). Here we report a more targeted approach to the
      characterization of nuclear genes from archaeological specimens. The Windover
      pond of central Florida has provided skeletal and soft tissue remains from 165
      humans, radiocarbon-dated to be 6,990-8,130 years old. Using DNA obtained from
      one individual we have characterized segments from six nuclear genes: that for
      beta 2-microglobulin and five members of the class I HLA heavy chain gene family.
      Distinctive patterns of nucleotide substitution in the cloned heavy chain gene
      segments permit tentative assignment of the HLA-A,B type of the ancient
      individual.

PMID- 2000148
TI  - Lexical organization of nouns and verbs in the brain.
AB  - The analysis of neuropsychological disorders of lexical processing has provided
      important clues about the general organization of the lexical system and the
      internal structure of the processing components. Reports of patients with
      selective dysfunction of specific semantic categories such as abstract versus
      concrete words, living things versus inanimate objects, animals, fruits and
      vegetables, proper names and so forth, support the hypothesis that the neural
      organization of the semantic processing component is organized in these
      categories. There are reports of selective dysfunction of the grammatical
      categories noun and verb, suggesting that a dimension of lexical organization is
      the grammatical class of words. But the results reported in these studies have
      not provided unambiguous evidence concerning two fundamental questions about the
      nature and the locus of this organization within the lexical system. Is the noun
      verb distinction represented in the semantic or in the phonological and
      orthographic lexicons? Is grammatical-class knowledge represented independently
      of lexical forms or is it represented separately and redundantly within each
      modality-specific lexicon? Here we report the performance of two brain-damaged
      subjects with modality-specific deficits restricted principally (H.W.) or
      virtually only (S.J.D) to verbs in oral and written production, respectively. The
      contrasting performance suggests that grammatical-class distinctions are
      redundantly represented in the phonological and orthographic output lexical
      components.

PMID- 2000149
TI  - Protein synthesis required to anchor a mutant p53 protein which is temperature
      sensitive for nuclear transport.
AB  - The p53 protein is rendered temperature-sensitive by a point mutation. Rat cells
      transformed by this mutant p53 and an activated ras oncogene grow well at 37
      degrees C but cease DNA synthesis and cell division when shifted to 32 degrees C.
      Immunostaining demonstrates that the mutant p53 protein is in the nucleus of the
      arrested cells at 32 degrees C but in the cytoplasm of the growing cells at 37
      degrees C. This is the first example of a protein which is temperature-sensitive
      for nuclear transport. The translocation from cytoplasm to nucleus and vice versa
      occurs 6 h after temperature shift and is coincident with the inhibition of DNA
      synthesis; transport from cytoplasm to nucleus does not require protein
      synthesis. Remarkably, inhibition of protein synthesis at 37 degrees C also
      results in the rapid appearance of mutant p53 in the cell nucleus. These results
      suggest the presence of a short-lived protein responsible for holding p53 in the
      cytoplasm at 37 degrees C but not at 32 degrees C. Analysis of a non-temperature
      sensitive mutant p53 protein shows that its cytoplasmic location is sensitive to
      protein synthesis inhibitors but not to temperature.

PMID- 2000150
TI  - Assembly of yeast Sec proteins involved in translocation into the endoplasmic
      reticulum into a membrane-bound multisubunit complex.
AB  - Secretory-protein translocation into the endoplasmic reticulum (ER) is thought to
      be catalysed by integral membrane proteins. Genetic selections uncovered three
      Saccharomyces cerevisiae genes (SEC61, SEC62 and SEC63), mutations in which block
      import of precursor proteins into the ER lumen in vivo and in vitro. The DNA
      sequences of SEC62 and SEC63 predict multispanning membrane proteins, and
      biochemical characterization of the SEC62 protein (Sec62) confirms that it is an
      integral ER membrane protein. Here we show that Sec61, Sec62 and Sec63 are
      assembled with two additional proteins into a multisubunit membrane-associated
      complex. These results confirm previous predictions, based upon genetic
      interactions between the SEC genes, that Sec61, Sec62 and Sec63 act together to
      facilitate protein translocation into the ER.

PMID- 2000151
TI  - High-speed DNA sequencing by capillary gel electrophoresis.

PMID- 2000152
TI  - [Direct surgical management of aneurysms in the cavernous sinus: a report of 5
      cases].
AB  - Five patients with aneurysms in the cavernous sinus were treated by direct
      surgical approach. Two small aneurysms were located in the C3 segment, one small
      aneurysm was on the primitive trigeminal artery (PTA), and the last two aneurysms
      were giant ones. The three small aneurysms were discovered incidentally by
      angiography and the two giant aneurysms presented oculomotor palsy. After
      ordinary fronto-temporal craniotomy, the two C3 aneurysms were treated through an
      intradural approach, and the PTA aneurysm and the two giant aneurysms were
      treated through combined epi- and subdural approach. The three small aneurysms
      were clipped and the two giant aneurysms were trapped with the reconstruction of
      ICA by saphenous veins. In all cases the aneurysms were excluded postoperatively,
      but in one giant-aneurysm case (Case 5) the bypass was occluded postoperatively,
      but the patient had no permanent neurological deficit. The four patients
      developed third nerve palsy and one developed fourth nerve palsy which resolved
      within 3 to 6 months. In one C3-aneurysm case (case i) the patient had loss of
      vision due to much packing in the medial side of the ICA. All patients were
      discharged and returned to their usual life. Three cases (case 2, 4, 6) are
      presented here and the problems of direct surgical management of aneurysms in the
      cavernous sinus are discussed with the related literature.

PMID- 2000153
TI  - [Choroid plexus tumors in infancy].
AB  - Twelve infants with choroid plexus tumors were reviewed retrospectively.
      Enlarging head circumference, bulging fontanelle, and vomiting were the major
      symptoms and signs appearing 2 to 5 weeks (mean = 3.7 weeks) before diagnosis.
      The average age at diagnosis was 7.7 months. Total removal was performed in 11
      patients with choroid plexus papilloma, and partial removal was achieved in 1
      patient with a choroid plexus carcinoma. A cerebrospinal fluid (CSF) diversionary
      shunt was placed temporarily in 6 infants and permanently in 4. Of the two
      patients not requiring CSF diversionary shunt, 1 needed a subdural-peritoneal
      shunt postoperatively. Histologically, 11 of 12 tumors were choroid plexus
      papillomas, and one was a choroid plexus carcinoma. All 12 patients were followed
      up for 4 months to 11 years (mean = 5.6 years). Eleven of 12 patients were alive
      at the time of their last check-up. All 11 survivors had normal psychomotor and
      neurological development. The treatment and outcome of choroid plexus tumors and
      management of associated hydrocephalus are discussed.

PMID- 2000154
TI  - [Cavernous malformation of the brain stem: clinical symptom and its surgical
      indication].
AB  - Clinical features and surgical indication of cavernous malformation (CVM) of the
      brain stem are reviewed, based on the analysis of five personally encountered
      cases and nineteen previously reported cases. Nineteen out of these twenty four
      cases presented sudden onset of neurological deficits suggesting brain stem
      hemorrhage. Although the majority of those patients with acute onset improved
      gradually within a couple of weeks, all cases, except for six cases treated with
      radical removal following their first bleeding episodes, presented recurrent
      hemorrhages, and one third of them died due to the repeated hemorrhages. The
      other six cases presented progressive neurological deficits with insidious onset.
      They were first diagnosed as brain stem gliomas or multiple sclerosis. All except
      two cases treated with radical removal of the CVM died within a year. Surgical
      indication of the cerebral CVM is still controversial, because its clinical
      presentations and natural history have been unclear. Recent clinical application
      of magnetic resonance imaging enables us not only to make a preoperative
      diagnosis accurately, but also to evaluate the operability in relation to its
      anatomical location. Because of an apparent disposition towards repeated
      hemorrhages, surgical removal should be considered for the symptomatic CVM in the
      brain stem, on which microsurgical manipulation would be possible with an
      acceptable risk in many cases.

PMID- 2000155
TI  - [Optimal hypervolemic therapy for symptomatic vasospasm].
AB  - Thirty-five patients with symptomatic vasospasm (SV) following aneurysmal
      subarachnoid hemorrhage (SAH) were managed according to a method based on
      hemodynamic manipulation, monitored by Swan-Ganz catheter. Nine out of these had
      delayed surgery. For those who developed SV, the pulmonary wedge pressure (Pcwp)
      and/or central venous pressure (CVP) were immediately increased up to the point
      at which neurological deficit was reversed by rapid injection of fresh frozen
      plasma, albuminates, low molecular dextrose, and glycerol. On this regimen,
      patients were closely observed for any neurological change. Then the hemodynamic
      parameters were maintained as optimal values until they could be reduced below
      optimal values without reappearance of neurological deficit. In inoperable
      patients, special attention was given in making a decision about discontinuing
      the regimen. The results were compared with thirty-seven patients with SV who
      were treated with conventional hypervolemic therapy (CHT) by continuous
      administration of albuminates. In the treatment of CHT, optimal values could
      hardly be established, so the same hemodynamic parameters were applied in all the
      cases. From this study, in the majority of the cases optimal values were found as
      follows: Pcwp up to 10-15 mmHg, and CVP below 11 cmH2O. On the contrary, in 20%
      of patients, neurological deficit was reversed by increasing CVP to a point not
      above 7 cmH2O. Correlation between neurological reversal and systemic blood
      pressure was not statistically significant. After this regimen (OHT), 74% of
      patients showed immediate improvement after volume expansion, and, in 80%,
      outcome was good, while 20% died. The motor function at the time of discharge was
      more than 3 on the manual test in all cases.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2000156
TI  - [Magnetic resonance imaging of posttraumatic syringomyelia and its surgical
      treatment].
AB  - Posttraumatic syringomyelia is an uncommon but significant late complication of
      spinal cord injury. It occurs in approximately 1.1 - 3.2% of cases of spinal
      injuries. With the increasing availability of CT and magnetic resonance imaging
      (MRI), the incidence of posttraumatic syringomyelia is increasing. The purpose of
      this report is to show MRI of posttraumatic syringomyelia and to assess the
      results of surgical treatment. Materials and Methods This series included 16
      cases of posttraumatic syringomyelia studied with MRI. 9 out of 16 cases showed
      delayed deterioration of neurological symptoms following spinal injuries. The
      interval between the trauma and the delayed symptoms of deterioration was from 2
      years 2 months to 32 years (mean, 8 years and 5 months). There were 13 men and 3
      women. The age ranged from 22 to 69 years, with a mean age of 42 years. The
      initial spinal cord injury was located in the lower cervical region in 4 cases,
      the thoracic region in 8, and the upper lumbar region in 4. All the patients were
      studied with resistive 0.15T system (Toshiba MRT 15 A) or a superconductive 0.5T
      system (Toshiba MRT 50 A) or a superconductive 1.5T system (GE Sigma or Siemens
      Magnetom). Six patients underwent 8 operative procedures for posttraumatic
      syringomyelia. Syringoperitoneal shunt was performed in 4 patients,
      syringosubarachnoid shunt in 3 and ventriculoperitoneal shunt in one. Results 1.
      MRI In all cases, the posttraumatic syringomyelia was easily diagnosed by MRI.
      The syrinx extended superiorly and/or inferiorly from the area of the old trauma.
      In 4 out of 16 cases, the syrinx extended into the medulla oblongata.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 2000157
TI  - [Subfrontal schwannoma: a case report].
AB  - A case of a 63-year-old woman with subfrontal schwannoma of the left side is
      presented. The patient had a two-month history of recent memory disturbance and
      unstable gait. Computed tomography represented an isodense mass lesion with large
      and small cystic components in the anterior cranial fossa, enhancing
      homogeneously after intravenous injection of contrast medium. Cerebral angiograms
      revealed a noticeable hypovascularity. She underwent total resection of the tumor
      on May 21, 1986. It was verified that the tumor was attached to the left
      olfactory groove and had invaded the ethmoid bone. It was suggested that this
      tumor arose from one of the meningeal branches of the trigeminal nerve or of the
      anterior ethmoid nerve. Histological examination proved that this neoplasm was of
      schwannoma.

PMID- 2000158
TI  - [Posterior fossa hemorrhage 11 years after the use of silastic dural substitute:
      case report].
AB  - A case of posterior fossa hemorrhage is reported. The hemorrhage occurred 11
      years after posterior fossa craniotomy with closure using a graft of silastic
      dural substitute. This 14 year-old girl underwent suboccipital craniotomy at the
      age of 3 years because of traumatic posterior fossa hemorrhage. The dura mater
      was repaired with a piece of dural substitute. Eleven years later, she developed
      severe headache and vomiting. Computerized tomography scanning revealed a high
      density area in the right posterior fossa. At exploration, a fresh clot was
      evacuated between the dural graft and the fibrous scar tissue. The resected
      fibrous scar tissue was 1cm thick, and was adhering to the duro glial scar
      tissue. Her postoperative course was uneventful, and she was discharged 2 weeks
      after surgery. Microscopic examination of the fibrous scar tissue revealed an
      outer layer of loose connective tissue with numerous capillaries. The inner layer
      consisted of dense connective tissue. It was speculated that fragile capillaries
      of fibrous scar tissue caused this hemorrhage. Surgeons should not forget this
      complication although silastic dural substitute is less used than it used to be.

PMID- 2000159
TI  - [A case of solitary syringobulbia].
AB  - A case of solitary syringobulbia without syringomyelia diagnosed by MRI was
      reported. A 63-year-old female, who had a history of progressive gait disturbance
      for 9 months, was admitted to our department because of severe headache.
      Neurological examination revealed that the patient was suffering from right
      pyramidal sign as well as left deep sensory disturbance without apparent
      impairment of cranial nerves or nystagmus. The somatosensory evoked potential
      stimulated by the left median nerve showed delay in latency and low amplitude,
      however, the auditory brainstem response showed normal records bilaterally. A
      syringobulbia associated with platybasia, basilar impression, obstructive
      hydrocephalus and Arnold-Chiari malformation was diagnosed by the
      neuroradiological examinations including plain X-ray films of the skull, CT scan
      and MRI of the brain. Subsequent to the decompression around the cisterna magna
      by suboccipital craniectomy and laminectomy of the atlas, the opening of the
      Foramen Monro which was obstructed by a thick membrane was carried out, and
      prevention of communication between the fourth ventricle and the syrinx was
      accomplished by using a piece of muscle. This operative procedure was thought to
      be compatible with Gardner's operation for syringomyelia. The patient showed
      gradual improvement of gait disturbance as well as headache 3 months after
      surgery, and this neurological improvement was proved by decrease in the size of
      the known syringobulbia on MRI, and by normalized somatosensory evoked potential
      stimulated by the median nerve. Pathophysiology of the solitary syringobulbia
      with relatively acute onset of the neurological symptoms was assumed to have
      taken place in the following manner.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2000160
TI  - [Surgical reconstruction of the proximal vertebral artery: vertebral to
      subclavian transposition].

PMID- 2000161
TI  - [Marked growth of arteriovenous malformation 19 years after resection: a case
      report].
AB  - We report a case of arteriovenous malformation (AVM) which recurred as a giant
      AVM 19 years after resection. At the age of 23, the patient underwent craniotomy
      for a small AVM with surrounding old hematoma in the right parietal lobe. The AVM
      was judged to have been removed completely on postoperative angiography, while
      abnormal small vessels were noted retrospectively. He did well until 19 years
      later when he had seizures. Repeated angiography showed huge recurrent AVM at the
      operative site. Considering the risk involved in surgery, he was discharged from
      the hospital with anticonvulsants. Recurrence of AVM after removal is rare, but
      patients with AVM surgery should be followed up with CT and angiography for a
      long period of time.

PMID- 2000162
TI  - [A case of intraosseous meningioma].
AB  - A case of intraosseous meningioma at the posterior fossa was reported.
      Intraosseous meningioma is very rate and only six cases have been reported in
      Japanese literature. A 64 year-old woman complained of progressive headache and
      was admitted to Ichinomiya Neurosurgical Hospital. On admission, neurological
      examination did not reveal any abnormalities. However, plain skull X-p showed a
      hyperostotic lesion in the right posterior fossa. CT scan demonstrated
      homogeneously enhanced mass by contrast medium. MRI showed a mass lesion of the
      posterior fossa on T1 and T2 weighted images. The right vertebral angiogram
      showed an avascular area in the right posterior fossa and no tumor stain. The
      tumor, which was partially attached to the underlying dura, was successfully
      removed surgically. The operative finding confirmed an intraosseous meningioma
      which had arisen from the right asterion. The post operative course was
      uneventful. Histological examination revealed fibroblastic meningioma.

PMID- 2000163
TI  - [Carotid-cavernous fistula successfully treated with embolization and radiation
      therapy: report of three cases].
AB  - Three cases of mixed internal and external carotid-cavernous fistula (CCF) were
      successfully treated with embolization of feeders from the external carotid
      artery (ECA) and focal irradiation to the cavernous sinus (CS). Cases 1 and 2
      were females, 63 and 69 years old respectively, both with spontaneous left CCF.
      Case 3 was a 55 year old male with posttraumatic left CCF. Symptoms of case 1
      were double vision, left chemosis and exophthalmos; those of case 2 were double
      vision, left retroobital pain, left forehead dysesthesia and blurred vision; and
      case 3 complained of double vision, left chemosis, left exophthalmos and
      pulsatile tinnitus. In all three cases, angiography disclosed left CCF fed by
      ipsilateral dural branches from the internal maxillary artery (IMA) and the
      internal carotid artery (ICA). In case 1, small branches from the ascending
      pharyngeal artery also fed the CS. In cases 2 and 3, feeders from the ECA were
      arising only from branches of the IMA. In case 3, hypertrophy of the
      meningohypophyseal trunk was visible. In cases 1 and 2, although the CS was
      opacified, feeders from the ICA were not clearly visible. Embolizations of
      branches of the IMA were performed in all cases using Ivalon under selective
      catheterization. In case 1, symptoms partially improved, but in cases 2 and 3,
      visual symptoms were transiently aggravated. Focal irradiation to the CS was done
      with total doses of 30, 30 and 40 Gy each for cases 1, 2, and 3 respectively. In
      case 1, clinical symptoms gradually improved about one third way through
      irradiation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2000164
TI  - [Neurocytoma in the left frontal lobe].
AB  - We report a case of a 7-year-old right-handed girl with neurocytoma in the left
      frontal lobe. She developed convulsive seizures on the right side of her face at
      the age of 1 year and 8 months, and CT scan revealed a low density lesion in the
      left frontal lobe near the Sylvian fissure. CT scan at the age of 7 years showed
      slight enlargement of the lesion in size, and linear calcification in the mass.
      MRI imaging revealed the lesion to be a solid mass involving the area of Brodmann
      44 of the left cerebral hemisphere. However, amytal test disclosed that her
      speech center was not situated in the left cerebral hemisphere. Subtotal removal
      of the tumor and removal of the epileptogenic focus were performed and no
      neurological deficits including speech disturbance resulted. The tumor was
      diagnosed as neurocytoma by electron microscopy. Because this tumor was
      considered of low malignancy, no radiation or chemotherapy was given. It is
      emphasized that neurocytoma can occur in parts of the brain other than in the
      ventricular system, though the incidence of the tumor is more frequent in the
      latter.

PMID- 2000165
TI  - [A case of human tail].
AB  - A human tail is a rare anatomical curiosity. A case of a human tail associated
      with lipomyelomeningocele is reported. The made subject was born, by breech
      delivery, at the 39th-week with a 3,008 g body weight. He was admitted to our
      hospital because of the presence of a human tail and subcutaneous mass in the
      midline lumbosacral region. The tail was about 7.5 cm in length and 2 cm in
      diameter. It was elastic and covered by normal skin. No systemic anomaly was
      found. Spina bifida below L5 was revealed, and no bony shadow was found on the
      plain X-ray film. CT scan showed a low density area in the spinal canal between
      L3 and lower sacral region that extended into the tail through the spina bifida.
      MRI also revealed intraspinal long T2 mass which was attached to the spinal cord
      and extended into the tail. Myelogram indicated intradural extramedullary mass
      below the L3 level. Surgical treatment was performed on the 3rd month of life
      with a diagnosis of a human tail with lipomyelomeningocele. At surgery, the tail
      was found to consist mainly of lipomatous tissue which extended subcutaneously
      and entered the spinal canal through the spina bifida. The tail and subcutaneous
      lipomatous tissue were totally excised. The capsule of subcutaneous lipomatous
      tissue was followed circumferentially down into the spinal canal, and found to be
      transformed to arachnoid membrane. Intradural lipomatous tissue was excised piece
      by piece, leaving only a small remnant attached to the conus medullaris to
      preserve sacral nerve root function.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2000167
TI  - [Study of esophageal transit with radioisotopes in the diagnosis of achalasia].
AB  - The investigations employed in the diagnosis of oesophageal achalasia have been
      assessed critically. Although electromanometry contributes most to diagnosis and
      pinpoints with absolute precision the physiopathological elements that
      characterise the disease, radioisotopic study of oesophageal transit is an
      important diagnostic aid. More readily than any other, this technique permits
      morphofunctional evaluation in selected patients; it also represents the most
      physiological investigation and the best tolerated and, second only to manometry,
      the most reliable. Oesophagography with baritate meal and oesophagoscopy also
      play a diagnostic role in oesophageal achalasia. The former makes it possible to
      document the cardial stop and the presence or otherwise of mega-oesophagus, the
      second excludes the presence of organic dysphagias and also has a therapeutic use
      because cycles of dilatation of the oesophago-cardial junction can be carried
      out.

PMID- 2000166
TI  - [Physiopathology and therapy of localized osteopenia].
AB  - Osteopenia is a condition of reduced bone mineral content including osteoporosis,
      characterised by a reduced bone mass but normal mineral composition of bone
      tissue, and osteomalacia, characterised by unchanged bone mass but a deficient
      level of calcification of the protein matrix. Both conditions possess
      multifactorial etiopathogeneses and may affect the skeleton as a generalised or
      local manner, thus creating syndromes of circumscribed osteomalacia (osteomalacia
      of the patella, of the jaw). In some cases of local osteopenia, genetic, ethnic,
      dietary (inadequate intake of calcium, vitamin D), behavioural (abuse of smoking,
      coffee or alcohol), mechanical (reduced muscular exercise) and jatrogenic factors
      can play an important pathogenetic role. The definition of the exact nature of
      osteopenia (osteoporosis or osteomalacia), now possible using instrumental and
      laboratory tests, and the identification of the pathogenetic factors involved
      enable a correct therapy to be commenced.

PMID- 2000168
TI  - [Physiopathology and clinical aspects of monoclonal IgM gammopathy].
AB  - Ten subjects with IgM monoclonal gammopathy were studied with particular
      references to their clinical pictures. In 7 cases, the M component was W's
      macroglobulinaemia (MW) and in 3 undetermined monoclonal gammopathy (UMG). Serum
      IgM was always greater than 2170 mg% in MW and greater than 1120 mg% in UMG. All
      patients were over 45. Haemorrhage and autoimmune phenomena were noted in 2/10
      cases, and liver and spleen enlargement in 7/10, peripheral lymphocytosis in
      5/10, marrow lymphoplasmacytosis in 7/10, and plasma hyperviscosity in 7/10. Beta
      2-microglobulin (beta-2MG) was higher on average in the 7MW cases than in the 3
      UMG. A monoclonal peak was observed casually in 2/10 and after it had been
      clinically suspected in 3/10. ESR was high in all cases. The clinical and
      laboratory data are interpreted in the light of the possible pathogenetic
      mechanism. In addition, stress is laid on their importance in the differentiation
      of these two forms of IgM monoclonal gammopathy.

PMID- 2000169
TI  - [Sensitivity, specificity and predictive value of body mass index for the
      screening of juvenile arterial hypertension].
AB  - On the basis of various epidemiological studies, the specificity, sensitivity and
      predictive value of different indicators of obesity and overweight in relation to
      risk factor of juvenile hypertension are discussed. These screening tests,
      although highly specific, lack in sensitivity. The Authors suggest that such
      tests could be considered as useful tools in school preventive medicine for the
      identification of subjects not at risk.

PMID- 2000170
TI  - [Indications for permanent electric electrostimulation in atrioventricular
      block].
AB  - Personal experience of pacemakers in patients suffering from (symptomatic and
      asymptomatic) 2nd degree AVB and 3rd degree AVB is reported.

PMID- 2000171
TI  - [Sexuality and rheumatic diseases. An investigation project].

PMID- 2000172
TI  - [Possibility of evaluation of chest pain at the time of hospitalization].
AB  - A series of 140 patients admitted to an Internal Medicine or a Cardiology
      Department for an acute chest pain is examined in order to evaluate the
      possibility of reaching a quick diagnosis, particularly for coronaric heart
      diseases, according with history, physical examination, electrocardiogram. In
      most of cases it was possible an immediate, correct evaluation of the patients,
      but in some cases a right diagnosis was achieved only after a period of
      observation and different investigations.

PMID- 2000173
TI  - [Increase of beta 2-microglobulin in drug addicts with anti-HIV antibodies and
      high risk of AIDS].
AB  - The beta 2-Microglobulin is a polypeptide present on the surface membrane of both
      B and T cells and is integrated into the structure of HLA antigenes. The beta 2
      Microglobulin concentration have been used as a reliable indicator of glomerular
      and tubular function of the kidney. Increased serum concentration of beta 2
      Microglobulin are observed also in lymphoproliferative disorders with high cell
      proliferation rates. More recently, increased concentration of beta 2
      Microglobulin was shown in patients with anti-HIV antibodies with or without
      symptomatic AIDS. We have determined beta 2-Microglobulin in 61 subjects: 40
      between the ages of 25 and 35 and seemingly healthy, 21 patients between the ages
      of 22 and 32 and intravenous drug abuser with anti-HIV antibodies and at high
      risk for AIDS. In all subjects we have tested: BUN, creatinine, beta 2
      Microglobulin and T4/T8 ratio. In 40 subjects as normal controls, beta 2
      Microglobulin average was means = 1.07 mg/L (SD = 0.39), T4/T8 ratio average:
      means = 1.06 (SD = 0.119). In 21 patients drug abuser with anti-HIV antibodies,
      the beta 2-Microglobulin average was cleanly increased: means = 4.72 mg/L (SD =
      2.23), the T4/T8 ratio average cleanly decreased: means = 0.54 (SD = 0.21). We
      believe the beta 2-Microglobulin quantitation, even if not specific for patient
      with symptomatic AIDS, used in conjunction with other laboratory tests,
      principally T4/T8 ratio, will be a useful marker for recognizing persons with
      possible asymptomatic AIDS who are members of populations known to be at high
      risk for AIDS.

PMID- 2000174
TI  - [HIV infection - neuropsychic disease. Ability to act and informed consent.
      Modalities of medical intervention].

PMID- 2000175
TI  - [Australian method of first aid for European snake bites. Spreading its use in
      Italy].
AB  - Antiquated first-aid procedures, such as the incision and sucking of the wound
      and the application of a tourniquet, are still used in Italy consequent to the
      bite of vipers. The A. hope that such procedures will be finally abandoned, since
      they are ineffective, impractical, painful and can furthermore produce
      invalidating or disfiguring permanent outcomes. In this report they extensively
      describe Australian first-aid measures consequent to snakebites, constituted by a
      compressive bandage and by immobilization of the bitten limb by splinting. They
      hope therefore that the divulgation of this procedure in Italian will bring
      about, within a short period of time, its extensive use in Italy consequent to
      viper bites, as it is very effective, practical and easy to carry out.

PMID- 2000177
TI  - [Treatment with indobufen of platelet hyperaggregation in a group of patients
      with vascular diseases].
AB  - Twenty-five patients with enhanced spontaneous platelet aggregation and impaired
      arterial or venous circulation syndromes have been treated by indobufen. Each of
      them received, by oral administration, 200 mg of the drug twice a day for periods
      of time from fifty one to hundred eleven days. This treatment normalized, in all
      the cases, the platelet aggregation. In eight patients of the group, three hours
      after the last drug administration, the average of the maximum platelet
      aggregation curves deflections, induced by ADP, epinephrine, ristocetin and
      collagen, resulted significantly reduced, while, in seven other patients, twelve
      hours after the last drug administration, only the aggregation curves induced by
      ADP and epinephrine resulted significantly inhibited. Most on the patients with
      arterial impairment syndromes noticed some improvements of their symptoms. Also
      the patients with light subjective post-phlebitic symptoms declared to feel
      better. The drug has been well tolerated. Therefore, its use is recommendable
      whenever it is advisable to get a full antiplatelet effect whose the prompt
      reversion might be required.

PMID- 2000176
TI  - [Effects of bicarbonated-alkaline water (Uliveto) on gastric and gallbladder
      emptying in normal subjects. Ultrasonic evaluation].
AB  - In 10 healthy patients gastric and gallbladder emptying after a standard meal
      (800 cal, 60% glucides, 20% protides, 20 lipids) associated with 400 ml alkaline
      bicarbonated water or tap water were evaluated by ultrasonography. An increase of
      gastric emptying was noted after alkaline bicarbonated water versus tap water
      with significant differences at 30' (p less than 0.05), 60' (p less than 0.01)
      and 120' (p less than 0.05). No significant differences exist in final gastric
      emptying time. Alkaline bicarbonated water induced less intensive gallbladder
      emptying with statistical difference versus tap water at 60' and 120' from the
      standard meal (p less than 0.01).

PMID- 2000178
TI  - [Rheologic effects of salmon calcitonin on post-menopausal osteoporosis. Results
      of a preliminary study].
AB  - The aim of this random blind vs placebo study was to assess the effect of salmon
      calcitonin (sCT) (100 UI/day intermuscular for 4 weeks) on the haemorheological
      pattern of 20 women, all non-smokers, aged between 50 and 65 years of age and
      affected by post-menopausal osteoporosis. Hematocrit, whole blood viscosity at
      high and low shear rates, plasma viscosity, red blood cell aggregation, dynamic
      deformation and viscosity were monitored. Our results show sCT ex vivo seems to
      act upon mechanisms regulating the plastic properties of the red blood cell
      membrane.

PMID- 2000179
TI  - [Earthenware and lead poisoning. Description of a case].
AB  - A case of acute lead poisoning caused by drinking wine that had been kept in a
      decorative amphora is reported. Chomico-physical analysis of the internal surface
      of the recipient evidenced a layer of lead paint very soluble in wine. It is
      hoped that this report will draw the attention of the practising physician and
      Preventive Medicine Departments to this unusual cause of saturnism. The craft
      production of earthenware recipients that have been inadequately glazed and their
      improper use as containers of drings of foods could be commoner than might be
      thought on the basis of the sporadic reporting of such cases of lead poisoning.

PMID- 2000180
TI  - [Changes in the thyroid hormone picture that may be found in severely
      decompensated type II diabetics].
AB  - Thyroid hormone picture of 28 patients (15 males and 13 females), mean age 56.6
      yr (range 45-65 yr), with seriously decompensated type II diabetes mellitus has
      been studied. In each patient the study was repeated after 3 months of treatment
      of diabetes. The patients showed significantly lower serum T3 levels and
      significantly higher serum rT3 levels (P less than 0.001), in comparison with a
      group of 16 normoglicemic subjects. After 3 months of strict control of diabetes
      T3 and FT3 significantly increased (P less than 0.01), whereas significant
      variations of rT3 were not found. Among the whole group of diabetics 5 patients
      had low levels of serum T4 (P less than 0.01 vs. controls), high levels of serum
      TSH (P less than 0.001 vs. controls) and an exaggerated responsiveness to
      exogenous TRH (P less than 0.001 vs. controls). After the 3 months of treatment
      these patients showed a significant decrease of rT3 (P less than 0.02) and of
      delta-TSH (P less than 0.01). In the whole group of diabetics significant
      statistical correlations between glycometabolic and thyroid parameters were not
      found. The study, on the whole, showed in patients with seriously decompensated
      type II diabetes, a hormone picture like the low-T3 syndrome, in some cases,
      however, pituitary TSH secretion suggested the existence of incipient failure of
      thyroid hormones. A connection between alterations in thyroid hormone picture and
      glycometabolic imbalance, even statistically labile, is however indicated by
      improvement of thyroid function when diabetes is carefully controlled.

PMID- 2000181
TI  - Vita brevis.

PMID- 2000183
TI  - Living wills.

PMID- 2000182
TI  - Squamous cell cancer of the larynx.

PMID- 2000184
TI  - The abiding validity of the Hippocratic oath.

PMID- 2000185
TI  - Aphorisms of Hippocrates.

PMID- 2000186
TI  - CVP catheter in thoracentesis.

PMID- 2000187
TI  - Pulmonary edema due to extreme left atrial compression.
AB  - Pulmonary edema is a common concomitant of valvular heart disease and ventricular
      dysfunction. In addition, left atrial dysfunction due to thrombus, myxoma, or cor
      triatriatum can produce the same clinical picture. We encountered a patient with
      intractable pulmonary edema secondary to obliteration of the left atrial cavity
      by an extrinsically compressing lung tumor. We believe extrinsic compression of
      the left atrium caused impaired left atrial filling, leading to pulmonary venous
      hypertension and pulmonary edema.

PMID- 2000188
TI  - Pleural effusions in AIDS.
AB  - The authors present clinical, radiographic, and laboratory findings, and the
      results of therapy for 16 patients with pleural disease and HIV infection. The
      study underscores the wide variety of etiologies of pleural effusions and
      recommends a stepwise pragmatic approach in evaluating such patients, making no
      distinction between non-HIV-infected subjects.

PMID- 2000189
TI  - Gastric hemorrhage and Kaposi's sarcoma treated with radiotherapy.
AB  - A 66-year-old man, with advanced alcoholic liver disease with Kaposi's sarcoma
      involving the stomach and the skin of the lower extremities, developed upper
      gastrointestinal hemorrhage. He was treated with radiation therapy to the stomach
      and the skin with rapid resolution of the gastric lesions, as demonstrated by
      serial endoscopy.

PMID- 2000190
TI  - Nodular intraperitoneal masses in a patient with cirrhosis.

PMID- 2000191
TI  - The use of mannitol in intracerebral bleeds in the medical ICU.
AB  - To determine the effects of mannitol osmotherapy, we reviewed patients admitted
      to the intensive care unit with a presumptive diagnosis of increased intracranial
      pressure. The conclusion from our 20-patient study revealed no significant
      therapeutic benefit using mannitol osmotherapy.

PMID- 2000192
TI  - Malpractice in the United Kingdom: a comparative approach.

PMID- 2000193
TI  - Electronic publishing: beyond browsing.

PMID- 2000194
TI  - The theory-research dialectic: a different approach.

PMID- 2000195
TI  - Rhythmicities.
AB  - The science of unitary human beings is explored in the context of the film "Wild
      Strawberries." The central concepts and the principles of the science are
      elaborated in the description of the character and experience of Dr. Borg as he
      is revealed in this film classic.

PMID- 2000196
TI  - The structure of nursing diagnosis from Orem's theory.
AB  - Nursing diagnosis is generally accepted as a legitimate part of the nursing
      process; however, there is no consensus on the form, structure, or meaning of
      diagnosis within the discipline. Some nursing theories and models provide the
      basis for deriving a structural model for nursing diagnoses. A general structural
      model for a classification schema for the perspective of Orem's general theory,
      the self-care deficit theory of nursing has been developed and described. Sample
      diagnostic statements for various levels within the schema are presented. The
      language of nursing diagnosis which is appropriate to the theoretical perspective
      is also described and examples are provided. Diagnostic statement models are
      identified. This work is the beginning of a formal classification system for
      nursing diagnosis from one nursing theoretical perspective.

PMID- 2000197
TI  - Phenomena for nursing science inquiry and the trinity of nursing.

PMID- 2000198
TI  - Perspectives on health.
AB  - On May 12, 1989, in Pittsburgh, six nurse leaders participated in a panel
      discussion on health at Discovery International, Inc.'s Nurse Theorist
      Conference. The participants were Imogene King, Nola Pender, Betty Neuman, Martha
      E. Rogers, Afaf Meleis and Rosemarie Rizzo Parse. The goal of the conferences was
      to present views on the meaning of health from different perspectives. The panel
      discussion provided the nurse leaders with an opportunity to engage in a dialogue
      about health. Five of the participants answered the questions posed and the
      conference keynote speaker Afaf Meleis responded. Four questions were posed to
      the panel relating to the meaning of health, the uniqueness of nursing, and nurse
      person relationships. The dialogue of the panel discussion follows.

PMID- 2000199
TI  - Existential-phenomenological foundations in nursing: a discussion of differences.

PMID- 2000200
TI  - The dilemma of nursing science: current quandaries and lack of direction.
AB  - The theme of this paper is the need to address the central question in nursing
      science. It is hypothesized that in the absence of a central, unifying question,
      the view of nursing as an applied science, the current research methodological
      debate, and the social policy statement definition of nursing have hindered
      nursing's ability to advance the science of nursing. The authors suggest that the
      terminology of applied science has been wrongfully interpreted as immediate
      application to nursing practice, that the research methodological debate has
      occurred because the focus of research efforts is on the means and not the end,
      and that the policy statement implies a stimulus-response approach to human
      behavior.

PMID- 2000201
TI  - Assessment of carbohydrate tolerance in pregnancy.
AB  - A review is given of the various methods of assessing carbohydrate tolerance in
      pregnancy. Oral glucose tolerance screening and diagnostic tests have been in use
      for more than 25 years. They are easily administered, relatively inexpensive, and
      present reasonable sensitivity; therefore, they continue to be used quite
      extensively. However, lack of reproducibility of the results and side effects
      such as nausea, vomiting, and headache have led to the use of alternate methods
      including glucose polymer (Polycose) and standard breakfast meals. These methods
      have been reported to present satisfactory results in clinical practice.
      Glycosylated hemoglobin (HbA1c) and fructosamine assays are also alternate forms
      of testing carbohydrate metabolism HbA1c measurement have been proven insensitive
      as a screening test for gestational diabetes, while their use as an index of
      overall glucose control remains valuable. The role of fructosamine in the
      assessment of carbohydrate intolerance remains controversial with conflicting
      claims made by various investigators regarding its sensitivity in detecting
      gestational diabetes and its response to alterations in glycemic control. In this
      review, the relative advantages and disadvantages of each glucose tolerance test
      are discussed and recommendations are given regarding their utility in pregnancy.

PMID- 2000202
TI  - Transvaginal sonography in infertility and assisted reproduction.
AB  - This review on transvaginal sonographic uses in the diagnosis and treatment of
      infertility evolves from the plethora of data acquired due to the renewed
      technology of TVS. A combination of its advantages: 1) closer proximity to the
      pelvic organs and therefore clearer images as compared to abdominal ultrasound,
      2) the avoidance of the necessity of full bladder made the TVS gain much
      popularity in obstetrics and gynecology. Its value is recognized not only by
      opening a door to early detection of common pathologies of pregnancy--ectopic
      gestation and fetal malformations, multiple fetuses, and spontaneous fetal
      reduction ("vanished twin"), but also made visualization of the enlarged
      fallopian tubes, uterine cervix and corpus and ovarian follicles an almost
      indispensible adjunct to modern gynecologic infertility workup. The value of TVS
      seems to increase tremendously not only as an indispensible diagnostic tool but
      also as a modern means of replacing laparotomy or laparoscopy for follicular
      aspiration and eggs retrieval for IVF/ET, GIFT and assisted reproduction,
      reduction of the number of multiple fetuses, and for treatment of most cases of
      ectopic pregnancy. Its value in the diagnosis and treatment of the infertile
      couple seems invaluable now and indispensible tomorrow.

PMID- 2000203
TI  - Computers and the law.

PMID- 2000204
TI  - Making health and fitness promotion work.

PMID- 2000205
TI  - Fitness to shout about.

PMID- 2000206
TI  - Stress in life and work. Part 4: Organisational factors (2).

PMID- 2000207
TI  - Healthy eating habits.

PMID- 2000208
TI  - Quality management. BS5750.

PMID- 2000209
TI  - Management and the OH nurse.

PMID- 2000210
TI  - Physician advertising. Ohio physicians speak out afer a decade of change.

PMID- 2000211
TI  - Substance abuse education: an essential supplement to medical school's
      curriculum.

PMID- 2000212
TI  - Dr. Herbert Morris Platter--the last statesman.

PMID- 2000214
TI  - [Educational reform in health care and nursing care: compromise with open
      questions...].

PMID- 2000213
TI  - Lady Godiva syndrome.

PMID- 2000215
TI  - [A working day of an operating room nurse].

PMID- 2000217
TI  - [Nursing education in The Netherlands].

PMID- 2000216
TI  - [Career spectrum: profile--operating room nurse].

PMID- 2000218
TI  - Tumorigenic transformation of spontaneously immortalized fibroblasts from
      patients with a familial cancer syndrome.
AB  - Immortal cell lines arose spontaneously during in vitro culture of initially
      normal fibroblasts, MDAH041 and MDAH087, from patients with Li-Fraumeni familial
      cancer syndrome. Fibroblasts from a control donor, MDAH170, maintained a normal
      morphology and senesced at 31 population doublings. The immortal fibroblasts have
      several properties of transformed cells. In addition to having acquired an
      altered morphology and chromosomal anomalies, MDAH041 and MDAH087 have escaped
      from senescence, growing beyond 300 and 100 population doublings (pd),
      respectively. As early as 50 pd, these cells can be transformed by an activated H
      ras oncogene to form tumors in nude mice. However, MDAH041 immortal cells were
      resistant to tumorigenic transformation by transfection with the v-abl oncogene.

PMID- 2000219
TI  - Differential expression of the LYL, SCL and E2A helix-loop-helix genes within the
      hemopoietic system.
AB  - The helix-loop-helix genes LYL, SCL and E2A are associated with chromosome
      translocations found in human lymphoid leukemias. To establish their
      hematopoietic expression patterns, we have isolated murine LYL and SCL cDNA
      clones and investigated the expression of all three genes by Northern blot
      analysis of 58 murine hemopoietic cell lines and tissues. The nucleotide
      sequences of LYL cDNA clones revealed alternative 5' untranslated sequences and
      differential splicing within the 5' portion of the coding region that may produce
      a LYL polypeptide lacking an N-terminal segment. The LYL gene was expressed in
      most myeloid, erythroid and B lymphocyte cell lines and displayed two alternative
      size classes of transcripts, the smaller size class (1.5-1.8 kb) being typical of
      the erythroid lineage and the larger class (2.0-2.3 kb) of the B cell lineage.
      These two size classes were found to differ in the 5' untranslated region. Thus,
      expression of the LYL gene appears to be differentially regulated in different
      hemopoietic cell types. In contrast, the E2A gene was expressed throughout the
      hemopoietic compartment as a single dominant transcript (3.5 kb). SCL expression
      was restricted to erythroid, mast and early myeloid cell lines, and the level of
      SCL transcripts (3.0 and 4.7 kb species) increased markedly during DMSO-induced
      differentiation of erythro-leukemia cells. Hence the SCL gene product may be an
      important regulatory factor for the erythroid lineage. The low or undetectable
      expression of both SCL and LYL in most T lymphoid cell sources is consistent with
      the view that the translocations of these genes in human T cell leukemias alter
      their normal regulation and may thereby contribute to neoplasia.

PMID- 2000220
TI  - Determinants of sequence-specific DNA-binding by p48v-myb.
AB  - The v-myb oncogene of the avian myeloblastosis virus encodes a nuclear protein,
      p48v-myb, which binds to DNA in a sequence-specific manner. We have used wild
      type and mutant forms of this protein expressed in E. coli to study the protein
      and DNA determinants for sequence-specific DNA-binding. We have shown that only
      the highly conserved domain at the amino terminus of p48v-myb is required for
      sequence-specific DNA-binding. However, neither of the tandem 50 amino acid
      repeats present in this domain is alone sufficient for such binding. We have also
      demonstrated that p48v-myb can recognize a single consensus myb binding site and
      appears to interact with DNA as a protein monomer. In addition, we have shown
      that sequence-specific binding by p48v-myb requires nucleotides which flank the
      previously reported PyAACT/GG consensus.

PMID- 2000221
TI  - Massive accumulation of neutral lipids in cells conditionally transformed by an
      activated H-ras oncogene.
AB  - Phenotypic consequences of ras oncogene expression were studied in cells
      conditionally transformed by T24 H-ras and a temperature-sensitive SV40 large T
      antigen (tsA58). Previous studies have demonstrated that transformation of REF52
      cells by ras and SV40 large T antigen requires continuous T antigen expression.
      Thus, tsA58/T24 H-ras transformants ceased growing when transferred to a
      restrictive temperature for T antigen expression. Inhibition of cell growth was
      accompanied by massive accumulations of cholesterol esters, triglycerides and a
      third lipid species, identified as glycerol ethers on the basis of mobility on
      TLC. Cholesterol esters were derived from serum lipoproteins, and appeared to
      accumulate because LDL receptor expression and activity did not decline in growth
      arrested cells. Triglycerides and glycerol ethers were products of cell
      metabolism. The process lacked features characteristic of adipocyte
      differentiation, but may suggest mechanisms important in diseases, such as
      atherosclerosis, that involve abnormal accumulations of neutral lipids.
      Accumulating lipid species may also include metabolites induced by ras that
      accumulate in growth-arrested cells.

PMID- 2000222
TI  - Identification of the ret proto-oncogene products in neuroblastoma and leukemia
      cells.
AB  - Monoclonal and/or polyclonal antibodies were generated against the products
      synthesized from two portions of the ret proto-oncogene (c-ret) cDNA expressed in
      Escherichia coli. These antibodies were reactive in immunoblotting with 150 kd
      and 170 kd proteins in cell lysates from three human neuroblastoma cell lines
      expressing the ret proto-oncogene. When the neuroblastoma cells were treated with
      tunicamycin, a protein with an apparent molecular weight of 120 kd, which is
      consistent with that of the c-ret protein predicted from the cDNA sequence,
      appeared on immunoblots. These results indicated that the 150 kd and 170 kd
      proteins in neuroblastoma cells are produced from a single polypeptide of 120 kd
      by posttranslational glycosylation. Furthermore, the antibodies detected a unique
      190 kd protein as well as 150 kd protein in a cell lysate from THP-1 human
      monocytic leukemia cell line, suggesting that glycosylated forms of the c-ret
      protein are different between neuroblastoma and leukemia cells.

PMID- 2000223
TI  - Preneoplastic lesions induced by myc and src oncogenes in a heterotopic rat
      colon.
AB  - With the use of viral vectors harboring myc and src oncogenes, we have assessed
      the potential contribution of these different elements to colonic neoplasia using
      a transplantation technique resulting in the formation of a heterotopic colon in
      Wistar Furth rats. While myc alone induced atypia and some dysplasia, src induced
      focal dysplastic lesions throughout the colon mucosa with evidence of metaplasia.
      In contrast, lesions induced by myc and src acting cooperatively, were highly
      dysplastic with evidence of tumor formation after protracted periods. These
      results indicated the formation of histologically distinct preneoplastic lesions
      elicited by the action of a single oncogene in colon implants with the production
      of adenocarcinomas when such oncogenic elements act cooperatively. This model
      provides an opportunity for studies of the action of different oncogenes, acting
      singly or in combination, in the multi-step progression to colon tumor formation.

PMID- 2000224
TI  - Somatic genetic changes on chromosome 18 in breast carcinomas: is the DCC gene
      involved?
AB  - Recently, a gene has been isolated from the long arm of chromosome 18 which was
      shown to be frequently deleted in colorectal carcinomas and hence designated the
      DCC gene (Fearon et al., 1990). To explore the possible involvement of this gene
      in breast cancer, we have used 5 polymorphic DNA markers (one for 18p, and four
      for 18q) to examine the status of chromosome 18 in 49 primary breast carcinomas
      by comparing the genotypes of lymphocyte and tumour DNA samples. Imbalance of
      alleles, resulting in allelic loss of duplication, was observed in 17 cases (38%
      of informative cases). In 13 of these, this imbalance included the locus D18S8
      located within the DCC gene region. In the remaining 4 cases this locus was not
      involved, with the affected chromosome region mapping proximally of D18S8 in 3
      cases, and distally in 1 case. These results indicate that chromosome 18 is
      rearranged in breast cancer more frequently than is expected on the basis of
      cytogenetic data alone, and warrant a closer inspection of the DCC gene in this
      tumour.

PMID- 2000225
TI  - The phosphorylation state of the retinoblastoma (RB) protein in G0/G1 is
      dependent on growth status.
AB  - The product of the retinoblastoma gene (RB) is a nuclear phosphoprotein which is
      thought to regulate the proliferation of cells. Its phosphorylation state changes
      with passage through the cell cycle and it has been proposed that RB protein in
      its hypo-phosphorylated form prevents cells proliferating. We have investigated
      the phosphorylation state of the RB protein in an actively-dividing human B
      lymphoblastoid cell line and after cell cycle arrest caused by alpha-Interferon
      (alpha-IFN). We show that the phosphorylation state of the RB protein in cells
      with 2N DNA content depends on whether the cells are actively cycling. Our data
      is compatible with the proposal that dephosphorylation of the RB protein allows
      cells to enter a quiescent state. This study sheds light on the molecular
      mechanisms which may mediate the cytostatic effects of alpha-IFN.

PMID- 2000226
TI  - Incidence of mutations at codon 61 of the Ha-ras gene in liver tumors of mice
      genetically susceptible and resistant to hepatocarcinogenesis.
AB  - By selective oligonucleotide hybridization of polymerase chain reaction (PCR)
      amplified tumor DNAs we have analysed the incidence of mutations at codon 61 of
      the Ha-ras gene in 42 liver tumors spontaneously developed in Balb/c, C3Hf and
      B6C3 male mice, and in 79 liver tumors induced by the chemical carcinogens
      diethylnitrosamine (NDEA) and urethan in B6C3 and B6C male and female mice. The
      incidence of Ha-ras gene mutations in both spontaneously developed and urethan
      induced liver tumors was 50%-63% in mice genetically susceptible to
      hepatocarcinogenesis (C3Hf, B6C3) and 7%-9% in mice genetically resistant
      (Balb/c, B6C). Urethan-induced tumors showed about the same incidence of ras
      mutations in male and in female B6C3 mice. NDEA-induced tumors showed a low
      incidence of Ha-ras mutations in both the hybrid mice (3/18 and 1/13 in B6C3 and
      B6C male mice, respectively). The most frequently found mutations were a C----A
      transversion at the 1st base of codon 61 in spontaneous tumors, and an A----T
      transversion at the 2nd base in urethan-induced tumors. Our results indicate that
      liver tumors induced by NDEA or urethan or spontaneously arisen have a different
      pattern of Ha-ras mutations at codon 61 and that these mutations constitute a
      rare molecular alteration in the pathogenesis of liver tumors in genetically
      resistant mice.

PMID- 2000227
TI  - Refined localization to contiguous regions on chromosome 10q of the two genes (H4
      and RET) that form the oncogenic sequence PTC.
AB  - In this report we confirm the localization of the human RET proto-oncogene to
      chromosome 10q11.2, both by Southern blot analysis of a panel of human-rodent
      somatic cell hybrids and by in situ hybridization on human metaphase chromosomes.
      Previously, we had assigned to the same chromosome region the gene termed H4. In
      about 25% of papillary thyroid carcinomas, this gene was shown to rearrange with
      RET to give rise to the transforming sequence PTC. The analysis of different cell
      hybrids containing subfragments of chromosome 10, in conjunction with pulse field
      gel electrophoresis, established that H4 is mapped distally to RET at a distance
      not less than 280 kb. These findings suggest that intrachromosomal rearrangements
      are responsible for PTC activation in papillary thyroid carcinomas.

PMID- 2000228
TI  - The COOH-domain of the product of the Saccharomyces cerevisiae SCD25 gene elicits
      activation of p21-ras proteins in mammalian cells.
AB  - The evidence presented here indicates that the domain containing the COOH
      terminal part of the Saccharomyces cerevisiae SCD25 gene product (C-domain),
      which is homologous to the COOH-terminal part of CDC25 protein, can elicit
      activation of mammalian ras proteins in CHO cells. Transfection of expression
      vectors carrying the C-domain of SCD25, but not of CDC25, promotes the GTP-bound
      form of ras proteins as determined by analysis of the guanine nucleotides bound
      to ras proteins immunoprecipitated by Y13-259 mAb, and enhances transcription of
      a HIV-LTR-CAT construct. This is the first demonstration of the activation of ras
      proteins by transfection of a single heterologous gene.

PMID- 2000229
TI  - Seizures: introduction and commentary.

PMID- 2000230
TI  - Febrile seizures: recent developments.

PMID- 2000231
TI  - An approach to the child with a first unprovoked seizure.

PMID- 2000232
TI  - The newer antiepileptic drugs: carbamazepine and valproic acid.

PMID- 2000233
TI  - Evaluation of children for epilepsy surgery.
AB  - Surgical management of refractory epilepsy in childhood is a viable treatment
      option available for many children. Ideally, this treatment should be applied to
      appropriate candidates prior to adulthood to prevent them from becoming
      "psychosocial invalids." The pediatrician is instrumental in identifying
      potential candidates for epilepsy surgery and referring them to a tertiary-care
      epilepsy center. Few detrimental long-term cognitive or behavioral deficits occur
      if the surgery is uncomplicated. The cost of the presurgical evaluation and
      surgical treatment varies from $25,000 to $100,000, depending on the preoperative
      work-up required.

PMID- 2000234
TI  - Treatment of the dehydrated child.

PMID- 2000235
TI  - Saying goodbye in the intensive care unit: helping caregivers grieve.
AB  - The need for critical care caregivers to complete their own grief work when a
      patient dies deserves special attention. Positive coping with grief and loss can
      be encouraged through formal programs and individual and group memorial services.

PMID- 2000236
TI  - Pediatric rehabilitation: from concepts to practice.
AB  - The field of pediatric rehabilitation nursing is a relatively new one in which
      professionals have raised many pertinent questions. A theoretical basis and an
      organizing framework are needed in this specialty field in order to assure that
      we are providing comprehensive and holistic care.

PMID- 2000237
TI  - Stigma in childhood chronic illness: a well sibling perspective.
AB  - The purpose of this study was to describe how well siblings view potential stigma
      in childhood chronic illness. Results of interview of 27 siblings are discussed
      using three major categories: revealing of the chronic illness to others,
      responses to the ill child, and impact of the illness on daily living.

PMID- 2000238
TI  - Visual acuity, binocular vision, and ocular muscle balance in VLBW children.
AB  - Thirty-four very low birth weight (VLBW) 6-year olds and 31 normal birth weight
      (NBW) 6-year olds were assessed for visual acuity, binocular vision, and ocular
      muscle balance. Significantly more of the children in the VLBW group failed the
      tests of binocular vision and ocular muscle balance. Failure in tests of
      binocular vision was associated with higher numbers of days on mechanical
      ventilation and higher number of days in the intensive care nursery during the
      first months of life.

PMID- 2000239
TI  - Care of pediatric patients sedated with pentobarbital sodium in MRI.
AB  - MRI is the optimum modality in imaging studies for diseases of the CNS and
      musculoskeletal systems. During MRI scans, no movement is allowed for 30-50
      minutes. Therefore most children under age 7 need to be sedated. Judicious use of
      pentobarbital sodium allows for safe and expedient MRI scans to be completed and
      requires nursing observation.

PMID- 2000240
TI  - Neonatal skin care: prevention of skin breakdown.

PMID- 2000241
TI  - Dysrhythmias in the pediatric AIDS patient.
AB  - Many organ systems are affected in the child with acquired immune deficiency
      syndrome (AIDS). The cardiac system can also become compromised by this disease.
      Pediatric nurses need to be able to recognize and interpret dysrhythmias in this
      group of patients.

PMID- 2000242
TI  - Intraosseous infusions.

PMID- 2000243
TI  - Nurse named administrative director of first international training program in
      pediatric AIDS.

PMID- 2000244
TI  - Consolidating middle management.
AB  - There are many forces in today's health care environment that nurse managers are
      confronted with on a day-to-day basis. The idea of a nurse manager managing more
      than one unit is not yet commonplace, but is indicative of a growing trend in
      nursing administration.

PMID- 2000245
TI  - Pediatric management problems: Henoch-Schonlein purpura.

PMID- 2000246
TI  - Liability for premature discharge: an update.
AB  - As first reported in the September/October 1988 issue of Pediatric Nursing,
      payors have taken an active role in the process of making discharge decisions in
      order to save money. Recent court decisions since the landmark Wickline v. The
      State of California case in 1987 have addressed this issue of shared liability
      between payors and providers.

PMID- 2000247
TI  - Singing the same song for access to health care.

PMID- 2000248
TI  - No greater gift than giving one's time.

PMID- 2000249
TI  - School health services: a Hub of Services to children and their families.
AB  - The Corporate/Community Schools of America (C/CSA) is a not-for-profit coalition
      of business executives, concerned educators, and community leaders working to
      reform urban public education in the United States. This article reports on the
      C/CSA Chicago and the Hub of Services, which is a central component of the school
      design. The Hub of Services concept is described and compared to traditional
      school health program management models. Selected outcomes of the program are
      summarized as well as replication issues. Given the competing demands for
      increased school-based services and increased fiscal constraints, this unique
      experiment provides a school health service model that offers a solution for both
      of these demands.

PMID- 2000250
TI  - Professional partnerships in primary care practice.
AB  - Professional partnerships in pediatric primary care produce opportunities for
      blending nursing and medical roles to offer optimal health care to children and
      families. During the Sixth Annual Pediatric Nursing Conference, held October 4-7,
      1990 in San Francisco, issues of role delineation, reimbursement or salary
      schedules, prescriptive authority, on-call status, malpractice coverage, and
      hospital privileges were discussed among a distinguished panel of PNPs and
      physicians.

PMID- 2000251
TI  - Needle stick injury in pediatric hospitals.
AB  - PURPOSE: To describe the type and source of employee needle stick injuries.
      METHODOLOGY: A retrospective survey of documents related to 42 needle stick
      injuries over a 6-month period. RESULTS: Nurses experienced the greatest number
      of sticks. The injuries occurred most frequently at the bedside and were most
      often associated with IV/parenteral therapy. CONCLUSION: Needle sticks were
      peripheral to the problem of product design.

PMID- 2000252
TI  - Production of interleukin-6 by fetal and maternal cells in vivo during
      intraamniotic infection and in vitro after stimulation with interleukin-1.
AB  - Amniotic fluid samples were obtained by transabdominal amniocentesis from 20
      women in preterm labor (less than or equal to 34 wk gestation). Concentrations of
      IL-6 in culture-positive amniotic fluids (mean 8706 pg/mL, range 5100-14,446
      pg/mL) were higher than those in culture-negative fluids (mean 1133 pg/mL, range
      15-6534 pg/mL, p less than 0.0001) or fluids from healthy term pregnancies (mean
      196 pg/mL, range less than or equal to 5-790 pg/mL, p less than 0.001). To assess
      possible sources of the Il-6 in amniotic fluid, we tested the ability of a
      variety of fetal and maternal cells to produce IL-6 in vitro after stimulation
      with IL-1, a cytokine known to stimulate IL-6 production. Very low concentrations
      of IL-6 were present in supernatants of cells not stimulated with IL-1; however,
      high concentrations were observed in supernatants of stimulated umbilical venous
      endothelial cells, decidual cells, and fetal and maternal blood mononuclear
      cells. To determine whether cells from adults produce IL-6 with kinetics similar
      to those of neonates, we incubated mononuclear cells obtained from blood of
      adults and term and preterm neonates with IL-1. After 6 h, IL-6 was detected in
      supernatants of adult cells and term neonatal cells, but not in supernatants of
      preterm cells. Concentrations at 18, 24, and 48 h were similar for adult and term
      cell supernatants, but were lower in supernatants of preterm cells. We also
      observed considerably more IL-6 mRNA accumulation in circulating mononuclear
      cells from adults than in those from neonates.

PMID- 2000253
TI  - Immunogenicity of Haemophilus influenzae type b conjugate vaccines in infant
      rhesus monkeys.
AB  - Two Haemophilus influenzae type b (Hib) polysaccharide-protein conjugate vaccines
      were evaluated for immunogenicity in eliciting anti-polyribosyl ribitol phosphate
      (PRP) antibodies in infant rhesus monkeys. Animals received intramuscular
      injections of either Hib polysaccharide (PRP)-meningococcal outer membrane
      protein complex or Hib oligosaccharide-CRM197 (HbOC) conjugate vaccines on d 0,
      28, and 56. Because HbOC contains the CRM197 mutant diphtheria toxin from
      Corynebacterium diphtheriae as its protein carrier, the effect of simultaneous
      injection of diphtheria toxoid on the immunogenicity of HbOC also was evaluated
      by dividing monkeys vaccinated with HbOC into three groups: HbOC/saline,
      HbOC/diphtheria and tetanus toxoids, and HbOC/tetanus toxoid (coadministration of
      HbOC and other vaccine or placebo injected into the flank muscle of different
      legs). Infant monkeys vaccinated with the PRP-outer membrane protein complex
      conjugate responded with anti-PRP antibody after the first dose and showed
      booster responses after the second and third injections. In contrast, infant
      monkeys vaccinated with HbOC did not respond after three doses of HbOC/saline or
      HbOC/tetanus toxoid. However, two of three monkeys given concurrent injections of
      HbOC and diphtheria and tetanus toxoids did respond. The nonresponder monkey to
      three doses of HbOC and diphtheria and tetanus toxoids did respond to a
      subsequent injection with PRP-outer membrane protein complex. Thus, concomitant
      administration of diphtheria toxoid, a common vaccine for human infants, is
      necessary to elicit an anti-PRP antibody response to HbOC.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 2000254
TI  - Developmental cellular electrophysiologic effects of d-sotalol on canine cardiac
      Purkinje fibers.
AB  - d-Sotalol may be a clinically useful class III antiarrhythmic agent for
      controlling ventricular arrhythmias in children. Because age-related differences
      in repolarization currents may contribute to developmental differences in
      response to antiarrhythmic agents that primarily affect repolarization, the
      electrophysiologic effects of d-sotalol were compared in Purkinje fibers from
      neonatal and adult dogs. Significant age-related changes characterized the
      antiarrhythmic profile of d-sotalol. d-Sotalol (10(-4) M) significantly prolonged
      the action potential duration of adult Purkinje fibers (310 +/- 8 to 380 +/- 7
      ms, p less than 0.01) and neonatal fibers (247 +/- 5 to 342 +/- 9 ms, p less than
      0.01). However, the lengthening of action potential duration was significantly
      greater in the immature age group. d-Sotalol had no significant effect on maximum
      diastolic potential, action potential amplitude, or phase zero upstroke velocity
      in normally polarized fibers. In contrast, different electrophysiologic effects
      were observed in K(+)-depolarized Purkinje fibers. Superfusion of adult K(+)
      depolarized fibers with d-sotalol suppressed excitability in five (38%) of 13
      fibers and significantly decreased action potential amplitude (88 +/- 2 to 83 +/-
      1 mV, p less than 0.05) and phase zero upstroke velocity (180 +/- 14 to 105 +/- 3
      V/s, p less than 0.01) in the other eight fibers. The membrane depressant effects
      observed in the younger age group were significantly less [no suppression of
      excitability and a smaller decrease in phase zero upstroke velocity (121 +/- 22
      to 101 +/- 23 V/s, p less than 0.05). The magnitude of action potential duration
      prolongation by d-sotalol in K(+)-depolarized fibers was less than in normally
      polarized fibers.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2000255
TI  - Autoregulation of brain blood flow during hypotension and hypertension in infant
      lambs.
AB  - To determine the limits of aortic blood pressure in infant lambs for
      autoregulation of global and regional brain blood flow, we studied 10 unsedated
      lambs during hypotension and 10 unsedated lambs during hypertension. In lambs 6
      to 13 d old, we produced graded changes in aortic blood pressure by inflating a
      balloon occluder placed around either the inferior vena cava or the descending
      aorta. Using radiolabeled microspheres, we measured global and regional brain
      blood flow at the baseline, and then with each graded change in aortic blood
      pressure. In an additional step, we administered atropine to determine if its
      antimuscarinic properties alter the fall in brain blood flow with severe
      hypotension, or alter the rise in brain blood flow with severe hypertension. We
      concluded that in the unsedated infant lamb, global brain blood flow remains
      stable between mean aortic blood pressures of 6.0 to 10.0 kPa (45 to 82 torr), a
      range from approximately 38% below to 12% above normal mean aortic blood
      pressure. We noted that this autoregulatory range is essentially unchanged from
      that described for the fetal lamb at 80% of term gestation--even though the mean
      aortic blood pressure rises during this period of maturation by more than 2.7 kPa
      (20 torr). We found that the lower limit of autoregulation varies among the
      different brain regions and is lowest in the thalamus, pons, and medulla. We saw
      little variation of the upper limit among the brain regions. Finally, we
      determined that atropine does not alter brain blood flow during severe
      hypotension or severe hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2000256
TI  - The effect of postnatal age on the adherence of enterohemorrhagic Escherichia
      coli to rabbit intestinal cells.
AB  - Enterohemorrhagic Escherichia coli (EHEC) are associated with hemorrhagic colitis
      and hemolytic uremic syndrome. These illnesses are typically seen in young
      children, but are rare before 6 mo of age. The cause of this age restriction is
      unclear. Because bacterial adherence to intestinal mucosa is considered a
      critical initial event in pathogenesis, we studied the ontogeny of the adherence
      of EHEC (O157:H7 and other serotypes) isolated from children with diarrhea,
      hemorrhagic colitis, or hemolytic uremic syndrome. Adherence was quantitatively
      determined by incubating radiolabeled bacteria with viable rabbit intestinal
      cells, which were prepared by treating loops of distal ileum and proximal colon
      with EDTA, DTT, and citrate. Cells obtained from animals of different ages were
      studied simultaneously. The adherence of the various EHEC strains varied
      significantly. A non-O157:H7 E. coli strain 43-12 bound best (35 and 32
      bacteria/cell to ileal and colonic cells, respectively) with 48-60% inhibition by
      D-mannose and alpha-methyl mannoside (p less than 0.01) and 20-28% inhibition by
      L-fucose (p less than 0.05), but no significant inhibition by other
      carbohydrates. Analysis of variance and polynomial regression showed that
      postnatal age significantly affected the adherence to ileal and colonic cells.
      Adherence during the 1st wk of life was 13-19% of that in the adult animal; it
      increased gradually, reaching the adult level at about 4 wk of age. Our study
      shows that postnatal age affects the adherence of EHEC to intestinal cells. These
      findings are compatible with postnatal development of gut receptors and may be
      relevant to the age-related risk of EHEC disease in children.

PMID- 2000257
TI  - Susceptibility of neonatal lipoproteins to oxidative stress.
AB  - We compared peroxidizability of neonatal and adult lipoproteins exposed to
      oxidative stress initiated by an azo-compound. Oxygen uptake showed a two-phase
      pattern, with slow oxygen uptake in the first phase and faster uptake in the
      second phase. During the first phase, tocopherol was consumed progressively,
      inhibiting lipid peroxidation by scavenging peroxy radicals. After the tocopherol
      concentration fell below a critical level, extensive propagation of chain
      oxidative reactions produced the rapid oxygen uptake in the second phase. In the
      first phase of neonatal lipoprotein oxidation, a faster oxygen uptake was
      observed and the length of this phase was shorter than in adults. The oxygen
      uptake rate in the second phase was smaller in the neonatal lipoproteins. In
      other words, neonatal lipoproteins were more susceptible to oxidative stress than
      were adult ones when tocopherol remained in lipoproteins, but after tocopherol
      depletion the reverse was true. These results were consistent with the finding
      that in neonatal lipoproteins the tocopherol/lipid ratio was significantly lower
      (length of the inhibitory phase was closely correlated to the lipoprotein
      tocopherol content). In addition, the average number of active bisallylic
      hydrogen atoms, which are considered to determine the relative susceptibility of
      polyunsaturated fatty acids to oxidation, was significantly smaller (oxygen
      uptake rate in the second phase was closely correlated to the active bisallylic
      hydrogen number) in neonatal lipoproteins, and the ratio of active bisallylic
      hydrogen to tocopherol content (which closely correlated to oxygen uptake rate in
      the first phase) was also significantly lower compared with the adult ratio.
      Under physiologic conditions, an intensive oxidation of lipoproteins sufficient
      to cause lipoprotein tocopherol to fall below critical levels is unlikely to
      occur.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2000258
TI  - Modulation of lingual lipase development by glucocorticoid in the rat.
AB  - Lingual lipase in the rat is present in the neonatal period and undergoes
      developmental increase during postnatal life. To evaluate the role of
      glucocorticoid in the control of lingual lipase during development, suckling rats
      were adrenalectomized at d 10 and various hormone replacements were performed.
      Adrenalectomy abolished the developmental increase of lingual lipase. Low doses
      of dexamethasone (0.2 and 0.5 microgram/100 g body wt) restored the lingual
      lipase to near normal level in adrenalectomized animals. High doses of
      dexamethasone (20 micrograms/100 g body wt), when given to similarly
      adrenalectomized animals, however, led to a reduction of lingual lipase levels.
      Inhibition by dexamethasone is through the action of the hormone inasmuch as the
      coadministration of RU38486, a glucocorticoid type II receptor antagonist,
      completely abolished the inhibitory action. Inhibition is also steroid specific,
      with dexamethasone and triamcinolone acetonide being more effective. The results
      suggest a unique bimodal regulation of lingual lipase by dexamethasone in the rat
      serous glands. Because of the possible importance of lingual lipase as an
      alternative enzyme for fat digestion in neonates, the inhibitory action of high
      doses of glucocorticoid on lingual lipase development may have important
      implications. The use of steroidal compounds in the hastening of lung maturation
      and treatment of inflammatory disease might conceivably compromise their lingual
      lipase development, hence their capacities of fat digestion and malabsorption in
      the same period.

PMID- 2000259
TI  - Hepatitis B virus mutants with precore-region defects in two babies with
      fulminant hepatitis and their mothers positive for antibody to hepatitis B e
      antigen.
AB  - Clones of hepatitis B virus (HBV) DNA were propagated from sera of two babies who
      developed neonatal fulminant hepatitis B, as well as from sera of their mothers
      who carried HBV with antibody to hepatitis B e antigen, and the precore-region
      sequences were determined. A point mutation from guanine to adenine, converting
      codon 28 for tryptophan (TGG) to a stop codon (TAG), was detected in 18 of 20 HBV
      DNA clones from mother and all 31 clones from baby in one family, and invariably
      in 55 clones from mother and three clones from baby in the other family. These
      results indicate that HBV mutants defective in the precore region in some carrier
      mothers with antibody to hepatitis B e antigen may transmit fulminant hepatitis B
      to their babies.

PMID- 2000260
TI  - Newly identified forms of electron transfer flavoprotein deficiency in two
      patients with glutaric aciduria type II.
AB  - Newly identified forms of electron transfer flavoprotein (ETF) deficiency in two
      patients with glutaric aciduria type II (GA II) were described. GA II has been
      attributed to a defect of either ETF or ETF dehydrogenase, resulting in multiple
      acyl-CoA dehydrogenation deficiency. ETF is a mitochondrial flavoprotein
      consisting of an alpha-subunit, alpha-ETF, and a beta-subunit, beta-ETF. We used
      pulse-chase experiments to examine the biosynthesis of ETF in fibroblasts from
      two patients with GA II. Patient 1 was a boy with the neonatal onset form, but
      without congenital anomalies, who is living at age 2 y. A defect of beta-ETF
      biosynthesis was noted in this patient. Patient 2 was a boy with the neonatal
      onset form with congenital anomalies who died on the 3rd postnatal day. He
      presented with a peculiar face and polycystic kidneys. In patient 2, both alpha-
      and beta-ETF were synthesized, but both the subunits were rapidly degraded. The
      lability of ETF was considered to be the cause of GA II in this patient. These
      two cases appear to be new forms of ETF deficiency in GA II.

PMID- 2000261
TI  - Importance of peroxisomes in the formation of chenodeoxycholic acid in human
      liver. Metabolism of 3 alpha,7 alpha-dihydroxy-5 beta-cholestanoic acid in
      Zellweger syndrome.
AB  - Infantile Zellweger syndrome belongs to the group of peroxisomal disorders that
      lack peroxisomes. Both trihydroxycoprostanic acid (THCA), the precursor to cholic
      acid, and dihydroxycoprostanic acid (DHCA), the precursor to chenodeoxycholic
      acid, accumulate in this disease. In previous studies, we have shown that liver
      peroxisomes are required for the conversion of THCA into cholic acid both in
      vitro and in vivo by measuring a defective conversion in infants with Zellweger
      syndrome. In our present study, the conversion of DHCA into chenodeoxycholic acid
      has been measured in an infant with Zellweger syndrome to evaluate the importance
      of liver peroxisomes for the formation of chenodeoxycholic acid. Coprostanic
      acidemia was present from the second day of life with high levels of THCA and
      only trace amounts of DHCA. The conversion of i.v. administered [3H]DHCA into
      chenodeoxycholic acid was only 7% compared with the 80% conversion in an
      analogous study in an adult. There was, however, a rapid incorporation of 3H into
      biliary THCA and, after a lag phase, the 3H was incorporated into biliary cholic
      acid. After 72 h, 15% of [3H]DHCA was converted to cholic acid. The pool size of
      DHCA was 1.2 mg/m2 and the pool size of both cholic acid and chenodeoxycholic
      acid was markedly reduced. The renal excretion of cholic acid was more efficient
      than that of the less polar chenodeoxycholic acid. More polar metabolites of DHCA
      and THCA are formed in alternative metabolic pathways facilitating renal
      excretion of these toxic intermediates. We conclude that liver peroxisomes are
      essential for a normal conversion of DHCA into chenodeoxycholic acid.

PMID- 2000262
TI  - Body composition and energy expenditure in adolescents with cerebral palsy or
      myelodysplasia.
AB  - We measured body composition, resting metabolic rate (RMR), and total energy
      expenditure (TEE) in a group of adolescents with cerebral palsy (CP) and
      myelodysplasia (M) aged 13- to 20-y-old using indirect calorimetry and the doubly
      labeled water method. Fat-free mass (FFM), RMR, and TEE were significantly lower
      in both the CP and M groups than comparable measurements in a control group of
      normal adolescent males and females. The ratio of TEE to RMR did not differ
      between controls and ambulatory M and CP subjects. However, TEE/RMR was
      significantly lower in the nonambulatory M and CP subjects than in controls (p
      less than 0.01). Our data indicate that energy requirements are reduced in both
      populations because both FFM and activity are decreased. Although energy
      requirements were decreased in both groups, the relationships between FFM and
      body weight differed. FFM and body weight were significantly correlated with RMR
      only in the M group. These data suggest that the type of paralysis in a
      handicapped population may affect resting energy expenditure.

PMID- 2000263
TI  - Development of the transdermal potential of human skin.
AB  - The development of the transdermal electrical potential (TDP) with postnatal age
      was studied in neonates born at gestational ages of 25 to 42 wk. The TDP of
      neonates born at less than 28 wk gestational age was of similar magnitude over
      the whole skin surface when measured in the first 5 d of life (mean value -5.4
      mV; skin surface negative with respect to s.c. tissues). The TDP increased
      progressively with increasing gestational and postnatal age. The rate of increase
      of the TDP with postmenstrual age was not accelerated in neonates born
      prematurely. TDP values of infants born at term were lower than those of adults,
      but the sites of high and low TDP were similar in both term infants and adults.

PMID- 2000264
TI  - A forced perturbation method of assessing pulmonary mechanical function in
      intubated infants.
AB  - Short pulses in airway pressure were used to assess the pulmonary mechanical
      function of nine infants suffering acute respiratory distress syndrome or
      bronchopulmonary dysplasia. All patients were intubated, spontaneously breathing,
      and mechanically ventilated at the time they were examined. The endotracheal tube
      was disconnected from the ventilator and connected to a mechanical oscillator
      that produced brief pulses in airway pressure at a rate of two pulses/s. These
      pulses were applied to the infants airway for 20-30 s, at which time the infant
      was replaced on the ventilator. The mean airway pressure during the procedure was
      maintained at the level of the positive and expiratory pressure that was set on
      the ventilator. Two classes of patients were identified from the pulse response
      primarily by the presence or absence of a local resonance in the impedance
      spectra. Similar results were obtained in five other patients who were examined
      with zero mean airway pressure, suggesting that the pulse response is little
      influenced by changes in mean lung volume or total lung compliance. Patient
      classification appeared related to the duration of ventilation therapy and the
      transition from one class to another was consistent with the development of high
      peripheral airway resistance and significant volume shunting in the central
      airways. These results suggest that brief pulses in airway pressure can be used
      to detect changes in the pulmonary mechanical function of preterm infants that
      result from long-term ventilation therapy.

PMID- 2000265
TI  - Pulmonary clearance of norepinephrine in lambs.
AB  - The lungs play an important role in the metabolism of vasoactive substances
      including endogenous amines. The role of pulmonary clearance of circulating
      norepinephrine has not been well defined in the young lamb (7-8 d of age). Using
      radiolabeled tracer norepinephrine in acutely instrumented lambs, we determined
      the in vivo pulmonary clearance and spillover rate of norepinephrine under
      baseline and hypoxic conditions. The fractional extraction of norepinephrine, the
      percent removed on a single pass through the pulmonary circulation, was 23 +/-
      2%. The corresponding pulmonary clearance rate was 61 +/- 10 mL/kg/min and the
      net pulmonary norepinephrine removal rate was 0.41 +/- 0.14 nmol/kg/min. This
      clearance represented over 70% of whole body norepinephrine clearance. The
      spillover of synaptic norepinephrine was 0.22 +/- 0.13 nmol/kg/min. During
      hypoxia, animals showed significant increases in pulmonary artery pressure and
      resistance. Fractional extraction and norepinephrine decreased to 16 +/- 3%, p
      less than 0.005. Pulmonary clearance decreased to 31 +/- 7 mL/kg/min, and net
      pulmonary norepinephrine removal rate decreased to 0.27 +/- 0.07 nmol/kg/min.
      These results demonstrate that pulmonary clearance plays a significant role in
      norepinephrine clearance in 1-wk-old lambs. Alteration of norepinephrine
      clearance during physiologic states such as hypoxia may be important in the
      pathophysiology of altered pulmonary vascular resistance in newborn animals.

PMID- 2000266
TI  - Spatially localized magnetic resonance spectroscopy of the brains of normal and
      asphyxiated newborns.
AB  - Phase-modulated rotating frame imaging is a modification of magnetic resonance
      spectroscopy, which uses a linear radiofrequency field gradient to obtain
      spatially localized biochemical information. Phase-modulated rotating frame
      imaging was used to study regional cerebral energy metabolism in the brains of 9
      normal newborns and 25 newborns after birth asphyxia. Relative concentrations of
      phosphorus-containing metabolites and intracellular pH were determined for brain
      tissue at three specified depths below the brain surface for all neonates. Wide
      variations in metabolite ratios were seen among normal neonates, and considerable
      metabolic heterogeneity was demonstrated in individual neonates by depth-resolved
      spectroscopy. Asphyxiated neonates with severe hypoxic-ischemic encephalopathy
      and a poor neurodevelopmental outcome showed the expected rise in inorganic
      orthophosphate and fall in phosphocreatine concentrations in both global and
      spatially localized spectra. Phase-modulated rotating frame imaging showed that
      metabolic derangement was less in superficial than in deeper brain tissue. The
      inorganic orthophosphate-adenosine triphosphate ratio from 1 to 2 cm below the
      brain surface was more accurate than any global metabolite ratio for the
      identification of neonates with a poor short-term outcome. These data are
      consistent with the known vulnerability of subcortical brain tissue to hypoxic
      ischemic injury in the full-term neonate.

PMID- 2000267
TI  - Anabolic steroid education and adolescents: do scare tactics work?
AB  - The opinions (level of agreement) of high school varsity football players with
      regard to reported effects of anabolic steroids were assessed before and after
      two different education interventions. Lectures and handouts of a balanced
      education program (potential risks and benefits) were compared with a risks-only
      (negative or "scare tactics") presentation, in a controlled manner. Those
      receiving the balanced review significantly increased their agreement with 5 of
      10 targeted adverse effects, while no change occurred for any risks among those
      taught by the negative intervention. A teaching model that only emphasizes the
      untoward consequences of anabolic steroids is ineffective, even in the short
      term. A balanced education approach can improve understanding of the potential
      adverse effects of these drugs. Additional strategies may be required to change
      young athletes' attitudes toward anabolic androgenic steroid use.

PMID- 2000268
TI  - Diphtheria-tetanus-pertussis vaccine and serious neurologic illness: an updated
      review of the epidemiologic evidence.
AB  - A widespread impression that DTP vaccine does cause brain damage has been based
      first on historical precedent--smallpox and rabies vaccines were recognized as
      sometimes causing devastating neurologic illness; analogy to pertussis--the
      disease can cause encephalopathy; and more recently on anecdotal evidence,
      particularly case series. A noncausal relationship--coincidence--could explain
      the temporal relation between DTP vaccine and neurologic illness, inasmuch as DTP
      vaccine is given at the age of emergence of idiopathic neurologic disease. The
      relationship between DTP vaccine and neurologic illness lacks specificity. Case
      series have had an impact on both physicians' and the lay public's impression of
      the safety of pertussis vaccine greatly out of proportion to their scientific
      importance. Case series can be useful for generating hypotheses but cannot
      provide evidence that pertussis vaccine is causally related to acute neurologic
      illness or brain damage. Observational studies using cohort and ecologic designs
      did not find an association between DTP vaccine and serious neurologic illness,
      but they were not powerful enough to detect an association as rare as that
      observed by the NCES investigators. The case-control design offers the best
      chance of providing causal evidence regarding DTP vaccine and serious neurologic
      illness. The NCES is the only published case-control study of this issue. This
      study found a rare association between DTP vaccine and some types of acute
      neurologic illness. Bias and chance are unlikely to account entirely for the
      association demonstrated by the NCES. However, the association has not yet been
      replicated by other case-control studies. The NCES does not demonstrate that DTP
      vaccine causes permanent brain damage.

PMID- 2000269
TI  - Maternal employment during the early postpartum period: effects on initiation and
      continuation of breast-feeding.
AB  - This study sought to determine whether and to what extent maternal employment in
      the early post-partum period is associated with the initiation and continuation
      of breast-feeding in a heterogeneous, urban population. A panel of women were
      interviewed twice during the first 3 months postpartum. In analyses adjusted for
      maternal demographic characteristics, there was no association between planning
      to be employed within the first 6 months postpartum and initiation of breast
      feeding. However, actually being employed was significantly associated with
      cessation of breast-feeding as early as 2 or 3 months postpartum, even after
      adjustment for maternal demographic variables. Less than one half of mothers who
      were employed were still breast-feeding at the second postpartum interview,
      whereas two thirds of those who were not employed were still breast-feeding.
      Among employed mothers, working no more than 20 hours per week appeared to be
      protective for continued breast-feeding.

PMID- 2000270
TI  - Immunologic defects in patients with refractory sinusitis.
AB  - Sixty-one patients with chronic sinusitis who were referred for an allergy
      evaluation were evaluated for immunologic competence including assessment of
      quantitative serum immunoglobulin levels, IgG subclass levels, and response to
      pneumococcal and Haemophilus influenzae vaccines. In addition to chronic sinus
      disease, recurrent otitis media and asthma exacerbation were common problems in
      this group. Five patients had an elevated age-adjusted IgE level and 22 patients
      had positive prick tests to one or more environmental inhalants; these findings
      suggest an allergic component in this subgroup. Twelve additional patients had
      highly reactive intradermal tests to common environmental allergens, which also
      may be clinically significant for underlying atopy. Eleven patients had low
      immunoglobulin levels, 6 had low immunoglobulin levels and vaccine
      hyporesponsiveness, and 17 had poor vaccine response only. Thus, 34 of 61
      patients with refractory sinusitis had abnormal results on immune studies, with
      depressed IgG3 levels and poor response to pneumococcal antigen 7 being most
      common. In addition to allergy, immunologic incompetence may be an important
      etiologic factor in patients with chronic, refractory sinusitis.

PMID- 2000271
TI  - Can clinical judgment detect children with speech-language problems?
AB  - Pediatricians often rely on clinical judgment derived from observation or
      parental concern to identify children with developmental problems. The less
      popular but recommended alternative is to repeatedly administer standardized
      screening tests. Such tests are time consuming but, unlike clinical judgment,
      have known detection rates. Preliminary research concerning clinical judgment
      showed that clusters of parental concerns related to their childrens'
      performances on screening tests. In the present study, previous research was
      refined by assessment of the meaning of parents' concerns about their childrens'
      speech-language development. In this study of 157 families seeking pediatric
      care, 72% of children whose speech-language screening yielded positive results
      had parents who were concerned about their speech-language development. Of
      children with negative screening results, 83% had parents with no concerns about
      their speech-language development. Although standardized screening tests should
      be used occasionally in the developmental surveillance process, the findings show
      that the problems of most children with developmental problems were detected
      through clinical judgment based on parental concern.

PMID- 2000272
TI  - Hypoglycemia, hypotonia, and cardiomyopathy: the evolving clinical picture of
      long-chain acyl-CoA dehydrogenase deficiency.
AB  - Inherited defects in fatty acid oxidation, which have been described and
      diagnosed with increasing frequency in the last decade, are most commonly
      attributed to a deficiency in the activity of medium-chain acyl-CoA
      dehydrogenase. Few cases of the related enzyme defect of long-chain acyl-CoA
      dehydrogenase activity have been reported. An infant with documented long-chain
      acyl-CoA dehydrogenase deficiency is described with a detailed metabolic profile,
      long-term clinical follow-up, and response to treatment. This patient is compared
      with the seven previously published cases of this disorder in order to stress the
      unique features of the initial presentation, more subtle late manifestations of
      the disease, and clinical and biochemical differentiation from the more common
      medium-chain acyl-CoA dehydrogenase deficiency. This report stresses the
      enlarging spectrum of the clinical presentation and natural history of this
      defect in fatty acid oxidation.

PMID- 2000273
TI  - Tilt test for diagnosis of unexplained syncope in pediatric patients.
AB  - Thirty-five teenage patients with a history of presyncope or syncope underwent a
      passive head-up tilting to reproduce symptoms of syncope. If tilting alone did
      not induce syncope, isoproterenol infusion was given to increase heart rate to
      150 to 160 beats per minute. In 80% of patients with a history of syncope,
      identical symptoms could be reproduced during tilting: an abrupt fall in blood
      pressure combined with profound nodal bradycardia, ranging from 32 to 86 beats
      per minute. These symptoms were quickly reversed by returning the patient to the
      supine position. For patients with frequent occurrences of syncope, especially
      when there was a history of trauma sustained during these episodes, a therapeutic
      regimen of either beta blockers or 9 alpha-fluorocortisol was begun. The
      mechanisms of this common cause of syncope in childhood is neurocardiogenic in
      response to venous pooling and catecholamine-induced tachycardia. The tilt test
      is an excellent and cost-effective test for the workup of unexplained syncope in
      childhood.

PMID- 2000274
TI  - Selenium in pediatric nutrition.
AB  - Se is an essential nutrient that provides antioxidant protection in concert with
      vitamin E. Several selenoproteins have been identified, but only one, SeGSHpx,
      has a known function, that of neutralizing toxic hydroperoxides. Plasma Se
      concentration, being responsive to changes in Se intake, is the most practical
      and widely used measure of nutritional Se status. The plasma Se concentrations of
      the majority of healthy infants and children fall within the range of 50 to 150
      micrograms/L. Although SeGSHpx activity measures the metabolically functional
      form of Se, the lack of a standardized analytical method has limited its
      usefulness as an index of nutritional Se status. Se deficiency was first observed
      in animals, but it is now recognized to occur in humans. Two human diseases
      associated with severe nutritional Se deficiency have been reported from China: a
      juvenile cardiomyopathy named Keshan disease and a chondrodystrophy named Kaschin
      Beck disease. Long-term TPN, which provides negligible amounts of intrinsic Se,
      has been demonstrated in some cases to result in biochemical and clinical
      impairment. Although there are no consistent signs and symptoms characteristic of
      TPN-associated Se deficiency in addition to the low blood selenium levels, some
      patients will experience leg muscle pain and altered serum transaminase and
      creatine kinase activities. These manifestation of Se deficiency usually take
      years to develop. Recent information about the amount of dietary Se needed to
      maximize plasma SeGSHpx activity in adult men has allowed for better estimates of
      the Se requirement for humans. Recommended daily dietary allowances published
      recently by the National Academy of Sciences have been revised for infants and
      children in this paper by making appropriate adjustments for the protein
      requirements of these age-groups. These recommended intakes for Se can generally
      be met by consuming adequate amounts of cereals, meat, eggs, dairy products,
      human milk, and infant formula, which are good sources of highly available Se and
      are of low risk of providing excess amounts of Se. Suboptimal Se intakes by
      pregnant women may predispose their infants to low Se status at birth, which in
      turn may affect the infants ability to maintain adequate Se status during the
      first few months of life. In those situations where protein intake is restricted,
      such as in phenylketonuria and maple syrup urine disease, Se-supplemented
      formulas should be used. The most critical situation for Se supplementation is in
      pediatric patients receiving long-term TPN therapy.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 2000275
TI  - Sweeteners, flavorings, and dyes in antibiotic preparations.
AB  - Even though a variety of adverse effects caused by sweeteners, flavorings, and
      dyes in susceptible individuals have been reported, there is no good single
      reference with information about these substances in pediatric antimicrobials.
      Data on sweeteners, flavorings, and dyes in 91 antimicrobial preparations were
      collected. Sucrose was present in 74 (85%) of 87 preparations, followed by
      saccharin in 30 (34%) preparations. Mannitol, lactose, and sorbitol were each
      present in 7 preparations. None of the preparations were free of sweeteners.
      Thirty-four (37%) of 91 preparations did not specify the flavoring content. While
      cherry was the most common flavoring used, there were 25 other flavorings.
      Thirteen different dyes and coloring agents were used in these antimicrobials.
      Red dye no. 40 was present in 45% of preparations. Tables detailing sweeteners,
      flavorings, and dyes in different groups of antimicrobials (amoxicillin,
      ampicillin, cephalosporins, erythromycin, penicillins, sulfonamides, and others)
      and adverse effects reported with these inert ingredients are presented. These
      tables should be helpful to physicians in selecting an antimicrobial containing a
      different sweetener and/or dye when an adverse reaction occurs.

PMID- 2000276
TI  - Breast-feeding among women attending women, infants, and children clinics in
      Georgia, 1987.
AB  - Breast-feeding is an important determinant of the health and nutritional status
      of children, particularly in lower socioeconomic populations. A major goal of the
      Georgia Special Supplemental Food Program for Women, Infants, and Children (WIC)
      is to increase the practice of breast-feeding among the women it serves. Breast
      feeding practices were determined among a random sample of 404 women from a
      cohort of 2010 who attended WIC prenatal clinics in Georgia in 1986 and were
      expected to deliver in February 1987. Respondents were interviewed 6 months
      postpartum. Of these women, 24% initially breast-fed, but only 6% continued for 6
      months or longer. The initiation of breast-feeding was associated with greater
      maternal education and with being married. The adjusted odds of breast-feeding
      for mothers who were married or living as married were 3.0 (95% confidence
      interval, 1.7 to 5.3) times greater than for mothers who were not married or
      living as married. Mothers with more than 12 years, 12 years, or 10 to 11 years
      of education were 5.2 (1.8 to 15.3), 2.7 (1.0 to 6.9), and 2.5 (0.9 to 6.9) times
      more likely, respectively, to breast-feed than mothers with 9 or fewer years of
      education. After adjustment was made for marital status and education, the
      remaining variables (ethnicity, parity, age, and employment status) did not
      influence the initiation of breast-feeding in this low-income population. The
      need for vigorous promotion of breast-feeding by the Georgia WIC program is
      emphasized by the low rate of initiation and short duration of breast-feeding in
      this low-income population.

PMID- 2000277
TI  - Neuropsychological outcome of pediatric liver transplantation.
AB  - Children with end-stage liver disease who undergo liver transplantation may have
      unrecognized neuropsychological and academic deficits, for which remediation
      programs may be available. Intellectual, academic, and neuropsychological
      measures of 28 pediatric patients who had received successful liver
      transplantation at least 1 year previously were compared with those of 18
      patients with cystic fibrosis (to control for effects of growth retardation and
      chronic illness) matched for age, age at diagnosis, physical growth, and parents'
      socioeconomic status. Liver transplant patients had significantly lower scores on
      nonverbal intelligence tests (mean +/- SD for liver transplant vs cystic fibrosis
      patients: 89.1 +/- 19.1 vs 105.8 +/- 17.6), lower academic achievement, and lower
      zeta scores for age in the areas of learning and memory (-0.68 +/- 1.09 vs 0.19
      +/- 1.24), abstraction and concept formation (-1.73 +/- 1.58 vs -0.79 +/- 1.37),
      visual-spatial function (-0.66 +/- 1.09 vs 0.10 +/- 0.69), and motor function (
      0.13 +/- 0.85 vs 0.36 +/- 0.57). No differences were found on tests of verbal
      intelligence, or in alertness and concentration, perceptual-motor, and sensory
      perceptual areas. Cyclosporine levels were found to correlate positively with
      motor speed (r = .41, P less than .05). Thorough psycho-educational and
      neuropsychological evaluations should be considered for pediatric patients who
      receive liver transplantation to allow these children to maximize their
      potential.

PMID- 2000278
TI  - Bovine surfactant replacement therapy in neonates of less than 30 weeks'
      gestation: a randomized controlled trial of prophylaxis versus treatment.
AB  - The influence of the timing of surfactant replacement therapy for the treatment
      of neonatal respiratory distress syndrome was evaluated in a study of 182
      neonates of less than 30 weeks' gestation who were randomly assigned prior to
      delivery to one of three study groups: control (dummy instillation of air given
      at birth), early surfactant (surfactant given at birth), or late surfactant
      (surfactant given at less than 6 hours of age). Subjects in the late surfactant
      group could avoid treatment if they had a clear chest roentgenogram and required
      no supplemental oxygen at a mean airway pressure of less than 7 cm of water. All
      treated neonates were eligible to receive up to three additional doses during the
      first 5 days of life. The three groups were comparable with respect to birth
      weight, gestational age, and other perinatal parameters with the exception of a
      lower cord arterial pH and 1-minute Apgar score in the early surfactant group. Of
      the 60 neonates randomly assigned to late treatment, 29 (48%) were deemed
      surfactant sufficient and thereby avoided treatment; the other 31 received their
      first dose at a mean age of 2.9 hours. There was a significant improvement in gas
      exchange during the first week of life in both surfactant groups compared with
      the control group, reflected by differences in fraction of inspired oxygen,
      arterial/alveolar PO2, and ventilation index (peak pressure x rate on the
      ventilator) (P less than .001). Surfactant therapy also resulted in a lower
      incidence of pulmonary air leak and severe chronic lung disease (defined as
      requirement for respiratory support beyond 36 weeks post-conceptional age). There
      were no differences between early and late surfactant groups in any of these
      parameters. The only statistically significant difference between the surfactant
      groups was that the early group had a higher incidence of mild chronic lung
      disease (respiratory support beyond 28 days of age) than the late treatment group
      (P less than .005). Neonates in the late treatment group were extubated earlier
      and had a shorter neonatal intensive care unit stay than control neonates (P less
      than .05), whereas those in the early group were not significantly different from
      control neonates in these parameters. It is concluded that replacement therapy
      with bovine lung surfactant extract in neonates of less than 30 weeks' gestation
      results in decreased oxygen and ventilatory requirements during the first week of
      life and a lower incidence of pulmonary air leak and severe chronic lung
      disease.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 2000279
TI  - Hypertension first seen as facial paralysis: case reports and review of the
      literature.

PMID- 2000280
TI  - VACTERL association with high prenatal lead exposure: similarities to animal
      models of lead teratogenicity.

PMID- 2000281
TI  - Compassionate pediatrics. Pediatrician mother's ordeal.

PMID- 2000282
TI  - I am my keeper; I am my brother's keeper.

PMID- 2000283
TI  - Poverty, WIC, and promotion of breast-feeding.

PMID- 2000284
TI  - American Academy of Pediatrics Task Force: Report on the future role of the
      pediatrician in the delivery of health care.

PMID- 2000285
TI  - Committee on Substance Abuse: "Smokeless cigarettes" and other nicotine delivery
      devices. American Academy of Pediatrics.

PMID- 2000287
TI  - 25% "error rate" in ear temperature sensing device.

PMID- 2000286
TI  - Outcome of less than or equal to 800-gram birth weight infants.

PMID- 2000288
TI  - Judging the validity of developmental screening tests.

PMID- 2000289
TI  - Fetal vascular disruption with prenatal exposure to cocaine or methamphetamine.

PMID- 2000290
TI  - Poison from the tap.

PMID- 2000291
TI  - Waiting in vain.

PMID- 2000292
TI  - New eye site.

PMID- 2000294
TI  - Cold comfort.

PMID- 2000293
TI  - Badly treated.

PMID- 2000295
TI  - A pill for every ill?

PMID- 2000296
TI  - Dropping the pilot.

PMID- 2000297
TI  - Gulf War. The vital links.

PMID- 2000298
TI  - Gulf War. Poised for rescue.

PMID- 2000299
TI  - Changing behaviour.

PMID- 2000300
TI  - Individual fears. Care study.

PMID- 2000301
TI  - Communication skills. A definite role.

PMID- 2000302
TI  - Nurses and the law. A hard lesson.

PMID- 2000303
TI  - Preparing children for admission to hospital.
AB  - This paper will discuss different ways of preparing children for the experience
      of hospital, the use of different methods to suit varying situations, how they
      relate to children of differing ages and the practicality of implementing such
      schemes.

PMID- 2000304
TI  - Workplace risks.

PMID- 2000305
TI  - Meeting of minds.

PMID- 2000306
TI  - Treating drug dependency.

PMID- 2000307
TI  - Alternative remedies during labour.

PMID- 2000308
TI  - Antenatal learning.

PMID- 2000309
TI  - HIV nurses go nationwide.

PMID- 2000310
TI  - Orthopedic nursing.

PMID- 2000312
TI  - Ambulatory surgery and prepared discharges. Effects on orthopedic patients and
      nursing practice.
AB  - Orthopedic medical and nursing practice has changed dramatically partly as a
      result of three trends: cost containment, technology, and consumer activism. Many
      orthopedic procedures previously requiring inpatient hospital stays are routinely
      performed on an outpatient, day-surgery basis. it is imperative that nurses
      working in the ambulatory surgery environment be diligent in practicing the
      nursing process to ensure comprehensive patient care. Patients requiring
      hospitalization for orthopedic procedures now have shorter lengths of stay. The
      brevity of stay means that a great deal of coordination, education, and referral
      efforts are necessary before the patient's discharge. Prepared discharge
      programs, with the nurse assuming the coordinator role, are one way of ensuring
      that patients are ready to make the transition from the hospital to their
      postdischarge environment.

PMID- 2000311
TI  - Congenital orthopedic anomalies and their impact on the family.
AB  - A baby born with a congenital limb deficiency presents a challenge to parents and
      health care professionals. Lack of information about treatment options can
      exacerbate the crisis for the family. The treatment modalities available to the
      family generally depend on the child's specific limb deficiency or deficiencies.
      Surgery to reconstruct the deficiency is not a workable option for many patients
      because of abnormal joints and soft tissues. Amputation may be recommended for
      patients whose deficiency is difficult or impossible to manage prosthetically.
      Limb lengthening is an option only for patients whose bones are smaller than
      normal. Prosthetics are the most widely used treatment modality because they
      immediately equalize limb lengths and improve function. When a baby is born with
      a congenital limb deficiency, the initial response of the parents is shock and
      denial. In adjusting to their newborn, they must first mourn the loss of the baby
      they expected. Once the adjustment process begins, specific information about the
      limb deficiency and the treatment options should be available. Family adjustment
      to the child is a continual process. As the child grows, management strategies
      need to change to adjust to the child's changing needs. With appropriate and
      timely health care and family intervention, a child with a congenital limb
      deficiency can be a happy, successful person.

PMID- 2000314
TI  - Sports nursing.

PMID- 2000313
TI  - Orthopedic complications. Compartment syndrome, fat embolism syndrome, and venous
      thromboembolism.
AB  - Specialized education in the care of orthopedic patients includes an
      understanding of the common complications for which patients require monitoring.
      With a socioeconomic backdrop of decreasing hospital stays and prospective
      payment, patient care must be managed proactively. For all three complications
      presented, there are unique sets of risk factors that, when present, contribute
      to a high index of suspicion for morbidity. Clusters of symptoms have also been
      discussed representing the expected normal patterns. With this knowledge as a
      foundation, clinical application is essential to incorporate other salient
      aspects of individual situations. Nurses diagnose and treat human responses to
      health problems. The end result of human responses to injury or orthopedic
      conditions can be the development of complications. Stringent adherence to
      patient monitoring protocols can promote timely nursing interventions to prevent,
      minimize, or detect complications or treatment side effects. Although definitive
      treatment is often physician directed, nurses are in a key role to impact final
      patient outcomes.

PMID- 2000315
TI  - Exercise physiology and cardiovascular fitness.
AB  - Endurance exercise training produces numerous metabolic and cardiovascular
      effects. Metabolic adaptations include an increase in oxidative capacity of
      skeletal muscle (greater number and size of mitochondria); an increase in
      skeletal muscle myoglobin concentration; a greater ability to oxidize fatty acids
      for energy; and an increase in stored glycogen. Cardiovascular effects of
      training include a decrease in resting heart rate and heart rate response to
      submaximal exercise; an increase in resting and exercise stroke volume; an
      increase in maximal cardiac output; an increase in VO2max; and an increase in
      arteriovenous oxygen difference. Aerobic exercise training contributes to
      cardiovascular fitness, because it beneficially alters the coronary artery
      disease risk profile. An inverse relationship exists between physical fitness and
      resting heart rate, body weight, percent body fat, serum cholesterol,
      triglycerides, glucose, and systolic blood pressure. In addition, exercise
      training increases the high-density lipoprotein fraction of total cholesterol.
      Endurance exercise is any activity that uses large muscle groups, can be
      performed continuously, and is rhythmic and aerobic in nature. To develop and
      maintain cardiovascular fitness, this exercise should be performed at a frequency
      of 3 to 5 days per week, an intensity of 60% to 90% HRmax or 50% to 85% HRmax
      reserve, and a duration of 20 to 60 minutes.

PMID- 2000316
TI  - Anterior cruciate ligament injuries. Evaluation, arthroscopic reconstruction, and
      rehabilitation.
AB  - The advantages of arthroscopic reconstruction of the anterior cruciate ligament
      tear over arthrotomy are quite obvious: reduced pain and morbidity. Some
      arthroscopists are performing these procedures on an outpatient basis. The
      physician can choose from several graft substitutes for anterior cruciate
      ligament replacement. Autografts consisting of the iliotibial band,
      semitendinosus, gracilis, and meniscus have been used as grafts. The most common
      autograft is the bone-patellar tendon-bone, which has been used since 1930 and
      has been shown to have a tensile strength near that of the anterior cruciate
      ligament. The state of the art in surgical alternatives for anterior cruciate
      ligament tears is arthroscopic reconstruction using the midthird of the patellar
      tendon. Treatment of anterior cruciate ligament injuries requires prompt and
      adequate evaluation of the laxity of the ligament as well as other structures in
      the knee, appropriate treatment options offered to the patient with complete
      descriptions of knee function after each treatment option, and comprehensive
      rehabilitation program. Patient compliance is an integral part of the success of
      this procedure. The nurse must include a description of the injury, preoperative
      testing, surgical intervention, and rehabilitation program when educating the
      patient. The successful postoperative anterior cruciate ligament rehabilitation
      program is multifaceted. In general, there must be specific guidelines applied by
      a physical therapist who has knowledge of the surgical procedure, understands
      principles of ligament healing, and has the ability to individualize the program
      as needed. For any level of athlete or active person, there must be achievement
      of all goals per phase to a high performance level. In addition, there must
      always be objective measurements to document progress to the physical therapist
      and physician but, perhaps most importantly, to reassure the patient that
      normalcy is being restored.

PMID- 2000317
TI  - Stress fractures in athletes.
AB  - Most stress fractures are preventable. Proper conditioning and preseason training
      is essential. Selection of the appropriate age-related sport must be taken into
      consideration. Adequate warm-up and cool-down is important to prevent muscle
      injuries that may contribute to stress fractures later on. The athlete should be
      aware of not "over-doing it" because fatigue is a contributing factor to the
      stress injury rate. Proper dress and equipment are necessary. Using the basic
      methods of prevention, along with good sportsmanship, safe participation in any
      sport may be anticipated. Because the demands and expectations of our high
      performance athletes are more prevalent, education and rehabilitation of the
      sports-injured patient have become ever important. With the emergence of sports
      medicine as a discipline, injured athletes are returned to the playing arenas
      much more rapidly with newer protocols and techniques. We must be ready rapidly
      to assess, diagnose, and treat all sports injuries; however, we must be aware and
      alert to the possibility that it is an injury of "wear and tear" when making any
      diagnosis and prescribing any treatment regime.

PMID- 2000318
TI  - Nursing management of the adolescent with idiopathic scoliosis.
AB  - Management of the adolescent idiopathic scoliosis patient has many intricate
      considerations. Whether the patient is braced or surgery is recommended, there is
      a lot of teaching, assessing, and compassion when dealing with adolescents whose
      biggest concern is being like their peers. It is important to allow as much
      independence in decision making as possible, whether it be about bracing or
      surgical intervention, as long as they clearly understand the consequences.
      Newer, better surgical instruments, anesthesia, nursing care, and postoperative
      mobility all have changed the management of the operative scoliosis patient
      significantly. Nursing assessment of neurologic, respiratory, function,
      emotional, and developmental needs of the adolescent patient, however, have not
      changed. If we, as nurses, understand the rationale for assessments, treatments,
      and restrictions, we can teach our patients and their families.

PMID- 2000319
TI  - Meniscal injuries.
AB  - The knee is the largest and one of the strongest joints in the body. It is used
      in all forms of vigorous activity and is relatively unprotected. This lends it to
      being one of the most injured joints in the body. In addition to being
      traumatized, there are several other forms of pathology that can manifest
      symptoms of pain, swelling, and instability. Fortunately, most of the problems
      can be treated with conservative methods or by arthroscopy.

PMID- 2000320
TI  - Diagnosis and treatment of shoulder injuries in the athlete.
AB  - The goal of the treatment team dealing with patients who have sports-related
      shoulder injuries is to return them to their previous activity. There is no
      substitute for knowledge of anatomy, diagnosis modalities, or current treatments.
      Realistically, some of the athletes are not able to return to the level of
      competition they performed originally. For those patients, recommendations and
      suggestions for alternatives based on a sound knowledge of arthroscopic
      principles need to be considered. One of the greatest roles for the nurse
      treating these patients may be the temporary loan of her shoulder for them to
      lean on.

PMID- 2000321
TI  - Common spinal injuries in athletes.
AB  - Special needs of athletes with spine injuries must be considered when planning
      for treatment of these patients. The patients wish to return to competition
      safely but rapidly. Nurses must understand the patients'/athletes' need but put
      them into perspective with respect to the diagnosis, treatment, and degree of
      disability. Support, encouragement, and understanding from a knowledgeable health
      professional are invaluable.

PMID- 2000322
TI  - Workplace health promotion programs. An overview.
AB  - The development of workplace health promotion programs is a popular trend in
      corporate America. The workplace is considered to have great potential for health
      promotion and education because workers spend more than 30% of their waking hours
      at work. Corporate managers are attracted by the broad claims of benefits made
      for workplace health promotion programs, which include improving employees'
      health and fitness; decreasing medical and disability costs; reducing
      absenteeism; improving job satisfaction; increasing productivity; and enhancing
      the corporate image. Although these claims are not proven through scientific
      research, current evidence suggests the workplace health promotion programs can
      have a positive impact on employees. The trend of increasing numbers of
      corporations establishing health promotion programs should continue in the
      future.

PMID- 2000323
TI  - The nursing role in limb salvage surgery.
AB  - Limb salvage surgery has proven itself as a valuable option for sarcoma patients.
      The reconstruction options are vast and include metallic implants, allografts,
      and a combination of both. The nursing implications for these patients are
      unlimited. The patient needs to be educated and assessed closely for
      complications such as infections, nonunion of the allograft, and limited
      mobility. Although the nursing care is more complicated, the rewards with working
      with these patients are great.

PMID- 2000324
TI  - That old hip. The osteoporosis process.
AB  - Osteoporosis is a major health concern that will contribute to an increasing
      number of hip fractures as the population ages. Researchers are continuing to
      evaluate the role that decreased level of estrogen at menopause and prolonged
      calcium insufficiency play in the development of osteoporosis. In addition, many
      health care recommendations are aimed at maximizing peak bone mass and preventing
      bone loss to decrease the chance of hip fracture. New studies are evaluating the
      efficacy of experimental medications to rebuild bone mass once osteoporosis has
      developed. Current prevention guidelines include adequate calcium and vitamin D
      intake and moderate exercise. At menopause, estrogen replacement therapy is
      recommended for those younger than 50 years or considered at high risk for
      developing osteoporosis. All people are encouraged to decrease the risk of
      fracture by evaluating their home environment for hazards that might contribute
      to falls. Nursing needs to develop new strategies and interventions to educate
      the public about osteoporosis, improve the quality of life for persons with
      osteoporosis, and decrease the osteoporotic hip fracture mortality rate. Will it
      rise to the challenge?

PMID- 2000325
TI  - Spinal stenosis. When arthritis is more than arthritis!
AB  - Spinal stenosis is the result of disc degeneration and narrowing accompanied by
      facet joint changes culminating in nerve root entrapment. Symptoms of back and
      leg pain appear gradually usually over a period of years and slowly worsen.
      Patients are usually in their 50s or older. Most patients are treated initially
      with nonoperative measures concentrating on pain relief and maintenance of
      activity. If the symptoms worsen, surgical intervention to relieve pain by
      decompressing the affected nerve roots is appropriate. Some patients with
      instability require a fusion. Most patients are satisfied with the results of
      surgery in relieving preoperative leg pain. Pain relief is often dramatic,
      allowing most patients to return to normal activity. Elderly patients tolerate
      this procedure surprisingly well. Old age alone should not be a contra-indication
      for this surgery. Therefore, the elderly should not be denied the benefits of
      surgical decompression. Nursing interventions can help these patients learn about
      spinal stenosis and assist them in pursuing appropriate treatment resulting in
      improved quality of living.

PMID- 2000326
TI  - Pelvic fracture patient care. Reflections on the past, implications for the
      future.
AB  - Nursing care of patients with pelvic fractures has changed dramatically in the
      past two decades. Fracture care that necessitated long periods of immobility and
      consequent complications has been influenced by new classification systems, the
      use of external fixation, and the more recent use of internal fixation. The
      evolution of pelvic fracture patient care has greatly influenced nursing care of
      these patients.

PMID- 2000327
TI  - Pain management in the orthopedic patient.
AB  - Pain is a familiar phenomenon to all orthopedic nurses. As Dunwoody said, "Few
      things we do for patients are more fundamental to the quality of life than
      relieving pain." We as orthopedic nurses are in a position to contribute to the
      positive management of pain by using a comprehensive approach to pain management
      that involves the participation of the patient. We need to believe the patient's
      pain, try new approaches, and help our patients achieve pain relief.

PMID- 2000328
TI  - Bone stimulators for fusions and fractures.
AB  - Even though a complete understanding of electrical responses of bone has not been
      fully obtained, useful data toward this end have been gathered. The development
      of devices that use what is known about the bone's electrophysiologic properties
      has impacted patient care. Many health care professionals remain skeptical about
      the effects of electrical stimulation in bone healing. Therefore, further
      research is needed to help the practitioner formulate a more educated opinion on
      this form of therapy.

PMID- 2000329
TI  - Choice of cases--with special reference to SIDS.

PMID- 2000330
TI  - Why do UK-born Pakistani babies have high perinatal and neonatal mortality rates?
AB  - A prospective study of 4934 babies of different ethnic groups has confirmed the
      high perinatal mortality rate for Pakistanis and has shown that this was not due
      to a reluctance to terminate a fetus who is known to be seriously malformed. The
      major cause of early mortality was a high rate of lethal malformations, which
      occurred in about 1 in 100 Pakistani babies and which accounted for about half of
      their perinatal mortality. Many of these were autosomal recessive and occurred
      only in the offspring of consanguineous parents. However, there was also an
      excess of lethal cardiac malformations which were not associated with parental
      consanguinity. The remainder of the excess perinatal mortality was probably due
      to socio-economic factors. These causes are partly amenable to preventive
      measures, such as the referral of Pakistani women for expert ultrasonography at
      18 to 20 weeks of pregnancy.

PMID- 2000331
TI  - The use of health services in the first 2 years of life in a nationwide cohort of
      very preterm and/or very low birthweight infants in The Netherlands:
      rehospitalisation and out-patient care.
AB  - In a prospective collaborative survey on very preterm (less than 32 weeks) and/or
      very low birthweight (VLBW) infants (less than 1500 g) in The Netherlands, the
      use of health services was studied by examining the incidence of and reasons for
      rehospitalisation and the use of out-patient care, i.e. visits to medical
      specialists and physical therapists. Out of 1338 liveborn infants originally
      enrolled in the survey, 998 survived the initial hospital stay. Their use of
      health services was studied during four period: discharge-3 months, 3-6, 6-12 and
      12-24 months corrected for expected date of delivery. A total of 320 infants
      (34%) was readmitted on 481 occasions. The main reasons for rehospitalisation
      were surgical procedures, of which inguinal herniorrhaphy was the most prominent,
      and respiratory tract disorders: 149 admissions (31%) and 147 (31%) admissions
      respectively. The remaining reasons for rehospitalisation occurred less
      frequently. In a multivariate analysis, both sex and the length of the initial
      hospital stay were shown to be significantly associated with an increased risk of
      rehospitalisation. During the study period, 671 children (67%) attended a medical
      specialist other than their paediatrician, and 313 children (31%) attended a
      physical therapist. The use of out-patient services was higher in the first than
      in the second year of follow-up. The use of health services depended very much on
      the neurodevelopmental status of the child. In the second year of life, a similar
      rehospitalisation rate and use of out-patient services was found in the non
      impaired children as in children from the general Dutch population.

PMID- 2000332
TI  - Infants with single umbilical artery studied in a national registry. General
      epidemiological characteristics.
AB  - In this paper, registry data on infants born in Sweden between 1983 and 1986 are
      reviewed to describe the epidemiological characteristics of infants with single
      umbilical artery (SUA). During this period 372,066 births were registered with
      information on the number of umbilical vessels. Our data set contains 1782 SUA
      infants. The incidence at birth was: in multiple births 0.8%, in infants with
      chromosome anomalies 6.1% and in singletons without a known chromosome anomaly
      0.46%. Incidence was higher in girls than in boys. There were no consistent
      seasonal variations in the date of presumed conception. Low birthweight (less
      than 2500 g) and preterm birth (less than 37 weeks) were seen more frequently in
      SUA singleton infants than in infants with three vessels. At any given gestation,
      SUA infants had a lower mean birthweight than infants with three vessels. The
      risk of having a SUA infant was increased in women over 40 years, and slightly
      increased at or above parity of three.

PMID- 2000333
TI  - Socio-economic factors associated with preterm delivery in Greece: a population
      based study.
AB  - A total population sample of singleton births to mothers with certain last
      menstrual period dates was identified from the Greek National Perinatal Survey of
      April 1983. Two groups were considered (3116 primigravidae and 6524
      multigravidae) with preterm rates of 5.9% and 8.4% respectively. Of all 17
      factors considered, primigravidae showed unadjusted significant associations
      between preterm delivery and marital status, region of mother's residence,
      maternal occupation, maternal education and paternal education level.
      Multigravidae preterm deliveries were associated with marital status, mother's
      age at marriage, father's age at marriage, mother's age at delivery, mother's
      education, father's education and maternal smoking at the end of the pregnancy.
      Logistic regression was used to identify the socio-economic and demographic
      characteristics independently associated with preterm delivery. For
      primigravidae, the only significant factors were maternal marital status and
      region of the country. For multigravidae, significant factors were maternal age
      at delivery, marital status and smoking habit at the end of pregnancy.

PMID- 2000334
TI  - Fumes from the spleen.

PMID- 2000335
TI  - Proportionality of small for gestational age babies as a predictor of neonatal
      mortality and morbidity.
AB  - Neonatal mortality and morbidity of 2609 babies who weighed less than the fifth
      centile for gestational age were studied in order to evaluate the relationship
      between the type of intrauterine growth retardation and the short-term prognosis
      after birth. Of these babies, 1175 had both a birthweight and head circumference
      below the fifth centile ('proportionately small'); the others, whose body weight
      was below but head circumference above the fifth centile, were defined as
      'disproportionately small'. The former group showed a consistently higher risk of
      death during the neonatal period. Morbidity defined by birth asphyxia,
      respiratory distress and neonatal infections was higher in those proportionately
      small babies who were delivered at term. The picture reversed for
      hyperbilirubinaemia, which was more frequent among disproportionately small
      babies. Proportionality, defined on the basis of the correspondence between
      birthweight and head circumference centiles, appears to be a simple and non
      invasive clinical method to identify babies who are at higher risk of adverse
      outcome.

PMID- 2000336
TI  - Perinatal mortality in southern Italy.
AB  - Perinatal deaths occurring in the Campania region of southern Italy in 1982 were
      analysed. The perinatal mortality rate was 17.6 per thousand (stillbirth rate
      8.3, early neonatal mortality rate 9.3). Compared with Swedish data, our deaths
      excess does not seem attributable to an unfavourable birthweight distribution,
      but to high birthweight mortality rates in every birthweight category and
      particularly in the normal birthweight group (greater than 2500 g). This group of
      newborns, representing about 94% of the births, contributes 45.4% of perinatal
      deaths; this situation is not common in developed countries, where the normal
      birthweight newborns form a much smaller proportion of perinatal deaths. The
      analysis of the causes of perinatal mortality, even though autopsies are rarely
      executed in Campania, shows a high prevalence of events which should be prevented
      by good antenatal and perinatal care.

PMID- 2000337
TI  - So what?

PMID- 2000338
TI  - Antenatal and perinatal care in southern Italy. I. The mothers' reports.
AB  - A population-based cross-sectional study of antenatal and perinatal care was
      performed in Campania, a region of southern Italy. One thousand three hundred
      women who had given birth in 1982 were interviewed. The number of antenatal
      visits was very low, less than 1% of the mothers having attended more than three
      times during pregnancy. The women at high obstetric risk did not attend more than
      those at low risk and certain aspects of their antenatal care were
      unsatisfactory. The place of birth was similar for high risk and low risk
      mothers, with 40% delivering in small private facilities (with few neonatal
      resuscitation facilities and often with inadequate infant transport services).
      The labour was induced or accelerated in 60% of the mothers. The organisation of
      perinatal care did not take into account many of the needs of the mothers such as
      presence of a relative at delivery, ambulation during labour, early relationship
      with the newborn, rooming-in, or encouragement to breastfeed.

PMID- 2000339
TI  - Antenatal and perinatal care in southern Italy. II. The clinicians' reactions.
AB  - One hundred obstetricians and 50 paediatricians engaged in public antenatal and
      perinatal care in southern Italy were interviewed about the provision of care in
      their facilities: 93% of the obstetricians judged the coverage of the target
      population to be insufficient and 53% of them considered the use of the risk
      approach to be unsatisfactory in public clinics. For example, no initiative was
      taken by 60% of public clinics when a woman at high risk failed to attend a
      booked antenatal visit. Bed rest during labour was prescribed by 72% of the
      obstetricians, a supporting relative was admitted to only 18% of the births and
      routine episiotomy was performed in 77% of primigravidae. Only 56% of the
      paediatricians interviewed allowed early contact between mother and baby. In
      public hospitals, 80% of paediatricians were present in the delivery room for the
      births. Screening for congenital hypothyroidism and phenylketonuria was executed
      in only 37% of the public hospitals. Newborn transport system adequate to
      national standards was available in only 33% of the hospitals. Antenatal and
      perinatal care need to be rapidly improved to meet population needs in southern
      Italy.

PMID- 2000340
TI  - The effects of smoking and drinking on the anthropometric measurements of
      neonates.
AB  - This study investigated the effects of smoking and alcohol consumption in
      pregnancy on length, head circumference, upper arm circumference and ponderal
      index, of neonates born to 1513 Caucasian women who delivered at St George's
      Hospital, south London. All measurements were adjusted for gestational age,
      maternal height, parity and sex of infant. Babies of smokers were shorter, had
      lower ponderal index and smaller upper arm circumference than those of non
      smokers. After controlling for alcohol consumption, these differences remained
      (but with reduced statistical significance). There was no statistically
      significant difference in head circumference between smokers and non-smokers.
      Alcohol consumption at booking had no effect on growth measurements in non
      smokers but had a significant, negative effect on all measurements in smokers.
      Drinking later in pregnancy had less effect. Alcohol appears to enhance the
      growth-retarding effect of smoking. It is suggested that both smoking and alcohol
      also have an inhibitory effect on fat deposition in babies, which contributes to
      the reduction in birthweight associated with smoking and drinking.

PMID- 2000341
TI  - Epidemiology and the woman in the street.

PMID- 2000342
TI  - Sudden infant deaths and cold weather: was the rise in infant mortality in 1986
      in England and Wales due to the weather?
AB  - Using the daily number of deaths due to sudden infant death syndrome in England
      and Wales from 1979 to 1985, and the daily temperature recorded at the London
      Weather Centre, two models were constructed, one including a temperature term and
      one without it, and the models used to predict the mortality in 1986. It was
      found that the model using temperature had a slightly better predictive power and
      successfully accounted for the increased mortality in February 1986. Thus, we
      conclude that the excess mortality of February 1986 was associated with the
      unusually cold weather during that month.

PMID- 2000343
TI  - Managing skin infections in children.
AB  - Because neonates and very young children have little or no immunity to common
      streptococci and staphylococci, skin infections caused by these organisms must be
      regarded warily. Prompt and proper treatment may be critical in preventing
      progression of the lesions and averting systemic complications.

PMID- 2000344
TI  - Traumatic vulvar hematomas. Assessing and treating nonobstetric patients.
AB  - Management of the vast majority of vulvar hematomas is conservative. Most resolve
      spontaneously when simple measures are taken. Serial examinations are necessary
      to distinguish uncomplicated hematomas from those requiring surgery. The
      clinician must also be vigilant for the possibility of sexual abuse and respond
      with appropriate workup and referral if this situation is suspected.

PMID- 2000345
TI  - Esophageal and gastric endoscopy in critically ill patients. How can it help you?
AB  - Bleeding from the upper gastrointestinal tract in a critically ill patient is a
      tough diagnostic situation. Endoscopy can help physicians determine the cause of
      bleeding and can also provide several therapeutic options. The authors discuss
      these applications of the current technology.

PMID- 2000346
TI  - Emergency resuscitation in children. The role of intraosseous infusion.
AB  - Intraosseous infusion is a temporary procedure for use in pediatric emergencies
      when intravenous access is difficult. Multiple drugs and fluids can be safely
      administered through the intraosseous route. Dosage and rate of infusion are
      essentially the same as with intravenous infusion.

PMID- 2000347
TI  - Abnormal liver enzyme levels. Evaluation in asymptomatic patients.
AB  - Chronic elevation of serum aminotransferase levels, even in the absence of
      symptoms, often reflects chronic hepatitis or other significant underlying liver
      disease. Patients with persistently abnormal alkaline phosphatase levels may have
      extrahepatic biliary tract disease or a chronic cholestatic disorder. Physicians
      can discover unsuspected liver disease without undue risk, expense, or
      inconvenience to the patient by means of the following: a carefully taken history
      and thorough physical examination, appropriate timing of follow-up blood tests,
      and timely referral for percutaneous liver biopsy or endoscopic retrograde
      cholangiopancreatography.

PMID- 2000348
TI  - Don't plagiarize--even yourself!

PMID- 2000349
TI  - Why patients delay seeking care for cancer symptoms. What you can do about it.
AB  - Patient delay in seeking care for cancer symptoms is common and well documented
      by research studies. Fear and denial, lack of information about cancer, and
      financial considerations all contribute to this delay. Patient education may be
      an important factor in decreasing the length of delay and thereby improving
      treatment outcome. By making good use of opportunities for patient education,
      primary care physicians may positively influence the prognosis of several types
      of cancer, particularly breast cancer and malignant melanoma of the skin.

PMID- 2000350
TI  - Charcot's disease in diabetic patients. Correct diagnosis can prevent progressive
      deformity.
AB  - Although Charcot's disease and its association with diabetes have been described
      many times in the literature, it is still often misdiagnosed and incorrectly
      treated as osteomyelitis, arthritis, or gout. The best safeguard is a high index
      of suspicion. A warm, swollen foot in a diabetic patient with long-standing
      neuropathy without local or systemic signs of infection must be considered
      Charcot's disease until proven otherwise. The principal treatment is total
      abstinence from putting weight on the foot until warmth, swelling, and redness
      subside. Protective weight-bearing methods may then be slowly instituted.

PMID- 2000351
TI  - Raynaud's syndrome. Using a range of therapies to help patients.
AB  - Raynaud's syndrome is a common medical problem. Approach to diagnosis must
      involve a search for underlying causes. Treatment includes avoidance of
      precipitating factors, biofeedback, and possibly pharmacologic therapy, after
      careful consideration of risks.

PMID- 2000352
TI  - Maxillary sinus hypoplasia masquerading as chronic sinusitis.
AB  - Maxillary sinus hypoplasia is a common condition that may be misdiagnosed as
      chronic sinusitis. Although hypoplasia can usually be seen on conventional sinus
      films, computed tomography may be necessary, as in the cases described by the
      authors in this article.

PMID- 2000353
TI  - Extracranial atherosclerosis and cerebrovascular disease. Minimizing the risk of
      stroke.
AB  - Extracranial atherosclerotic cerebrovascular disease is a risk factor for
      myocardial infarction and stroke. Asymptomatic patients with evidence of disease
      may benefit from modification of risk factors for stroke (ie, hypertension,
      hyperlipidemia, diabetes mellitus, and cigarette smoking). Symptomatic patients
      with focal brain ischemia may benefit from antiplatelet therapy, anticoagulation,
      and surgery in addition to modification of risk factors.

PMID- 2000354
TI  - Pancreatic pseudocysts. When to drain, when to wait.
AB  - Acute pain in the upper abdomen in a patient recovering from pancreatitis or
      abdominal trauma may herald a pancreatic pseudocyst. Although small cysts resolve
      spontaneously, those larger than 6 cm across usually require treatment to prevent
      such complications as rupture into adjacent structures and infection. The authors
      describe operative and nonoperative treatment methods and the success reported
      with each.

PMID- 2000355
TI  - Do you have patients with anorexia or bulimia? Understanding is the first step in
      helping.
AB  - Anorexia nervosa and bulimia nervosa have, in recent years, become disorders of
      major concern. Young women are particularly prone to such eating disorders, and
      substantial numbers have involved themselves in the practices that identify these
      problems. Understanding the thinking behind these disorders is helpful in
      recognizing them and developing a treatment approach. The most effective
      medication for bulimia reported to date is fluoxetine hydrochloride (Prozac). The
      concurrent participation of a physician, nutritionist, and family therapist in
      the care of these patients is ideal.

PMID- 2000356
TI  - Help for the hurting elderly. Safe use of drugs to relieve pain.
AB  - Pharmacologic management of pain in elderly patients is a common and difficult
      clinical problem. Because of altered drug metabolism and pharmacodynamics in the
      elderly, the drugs of choice are different than in younger patients and side
      effects occur more often. However, with judicious use and monitoring for
      toxicity, oral medications given as part of a multimodality approach can achieve
      adequate analgesia in most elderly patients.

PMID- 2000357
TI  - Alzheimer's disease. Clues to the cause.
AB  - Although Alzheimer's disease was described at the turn of the century, it has
      gained notoriety only in the past several decades. Interest in the disease has
      been catapulted forward by the dramatic increase in the number of elderly
      persons, the most rapidly expanding segment of the population. As the proportion
      of the aged population grows, so too will the medical and social consequences of
      the disease. Thus far, the most substantial leads in the search for a cause of
      Alzheimer's disease have been in the areas of genetic, biochemical, and
      epidemiologic research. While certain environmental factors such as aluminum have
      provoked interest, their role remains controversial.

PMID- 2000359
TI  - When to suspect connective tissue disease.
AB  - When a connective tissue disease is suspected, physical and historical data
      should be collected to build a case for a clinical syndrome. Negative serologic
      results may be helpful; positive ones must be used with awareness of their
      limitations. If a diagnosis is not clinically evident or serologically confirmed,
      observation may be preferable to overdiagnosis and unnecessary treatment. If the
      syndrome is atypical, physicians should look for evidence of clinical overlap and
      reevaluate regularly with an open mind.

PMID- 2000358
TI  - Chilaiditi's syndrome. A diagnostic challenge.
AB  - Chilaiditi's syndrome should be considered in the differential diagnosis of
      abdominal and chest pain. Although interposition of the right colon is a
      relatively common radiologic finding, there is a distinct paucity of information
      in the medical literature. Chilaiditi's syndrome is usually asymptomatic, but
      when symptoms occur, conservative treatment is usually effective. Recognition is
      important because this syndrome can be mistaken for more serious abnormalities,
      which may lead to unnecessary surgical intervention.

PMID- 2000360
TI  - Niacin caution.

PMID- 2000361
TI  - Mitral valve prolapse syndrome.

PMID- 2000362
TI  - Walking on glass.

PMID- 2000363
TI  - Premixed insulins. How do they compare with other insulin preparations?
AB  - With the availability of premixed insulins, physicians and diabetic patients have
      a wider choice of therapeutic options. The premixed preparation now available in
      the United States consists of 70% NPH insulin and 30% regular insulin. The major
      advantages of premixed insulins are convenience and improved accuracy. They are
      suitable for patients who are too impaired to mix their own insulin dose and for
      those whose mixed-dose ratio is similar to that of the 70/30 preparation.

PMID- 2000364
TI  - Intensive management of type II diabetes.
AB  - The goals of intensive treatment of type II diabetes are to restore blood glucose
      levels to normal; correct hyperlipidemia, hypertension, and other cardiovascular
      risk factors; and prevent hyperinsulinemia. Treatment should begin with attempts
      to reduce weight through diet and exercise. In fact, diet and exercise should be
      stressed as vital components of a diabetic patient's life-style no matter what
      treatment method is used. Drug treatment may consist of a sulfonylurea to
      increase insulin secretion and improve insulin resistance or of exogenous insulin
      to achieve glucose control and avoid the dangers of chronic hyperglycemia. A
      combination of the two appears attractive but is still under investigation.
      Control of hypertension is mandatory and may require use of an angiotensin
      converting enzyme inhibitor or calcium channel blocker. Normalization of serum
      lipid levels is also important in these patients, and agents that adversely
      affect glucose levels must be avoided.

PMID- 2000365
TI  - Portable blood glucose meters. Teaching patients how to correctly monitor
      diabetes.
AB  - Self-monitoring of blood glucose is an important component of treatment in
      patients with diabetes. Recent improvements in glucose meters have made patient
      self-testing more reliable and less dependent on user technique. However, success
      of the process depends on the training, reassessment, and support of the patient
      by the healthcare team.

PMID- 2000366
TI  - Peptic ulcer disease. How to treat it now.
AB  - Options for treatment of peptic ulcer disease are becoming more diverse. Most new
      agents are effective yet offer no real advantage over more traditional therapy.
      However, omeprazole (Prilosec) may be of benefit owing to its potent inhibition
      of acid secretion, but it is not yet approved for this purpose. Whether treatment
      of Helicobacter pylori infection will prove beneficial is not yet known, but the
      answer should be forthcoming. Finally, as with any disease process, alleviation
      of risk factors is always important. Appropriate counseling regarding use of
      nonsteroidal anti-inflammatory drugs and cigarette smoking is a necessity.

PMID- 2000367
TI  - Eliminated chromatin of Ascaris contains a gene that encodes a putative ribosomal
      protein.
AB  - Chromatin diminution in the nematodes Parascaris equorum and Ascaris lumbricoides
      leads to the formation of somatic cells that contain less DNA than the germ-line
      cells. We present molecular evidence for the coding potential of germ-line
      specific DNA. We report on a cDNA clone that codes for a putative ribosomal
      protein (ALEP-1, for A. lumbricoides eliminated protein 1). That the
      corresponding gene is located in the eliminated portion of the genome indicates a
      difference in germ-line and somatic ribosomes of A. lumbricoides and P. equorum.
      Elimination of the ALEP-1 gene from all somatic cells in its fully active state
      may represent an alternative way to gene regulation.

PMID- 2000368
TI  - Branching pattern in the evolutionary tree for human mitochondrial DNA.
AB  - Eighty-eight types of mitochondrial (mt) DNA were found by sequencing the most
      variable part of the control region from 117 Caucasians. In the tree relating
      those types, most of the branching events occur about two-thirds of the way from
      the root of the tree to the tips of the branches. Moreover, the distribution of
      sequence differences between all possible pairs of individuals is approximately
      Poisson. Other non-African populations show a similar pattern. Assuming a neutral
      model, these findings imply that the probability of survival of new lineages has
      undergone dramatic changes, probably due to population expansion. Conversely,
      African populations show multimodal distributions fitting with a model of
      constant population size.

PMID- 2000369
TI  - Monomeric IgG2a promotes maturation of bone-marrow macrophages and expression of
      the mannose receptor.
AB  - The macrophage mannose receptor, a 172-kDa lineage-specific glycoprotein,
      partakes in nonopsonin-mediated phagocytosis by recognition of terminal mannose
      residues on targeted particles. Because appearance of the receptor progresses
      with monocyte/macrophage differentiation, its expression is indicative of the
      maturational state of the cell. Monomeric IgG2a and IgG2b up-regulate mannose
      receptor surface expression and biosynthesis by murine bone-marrow macrophage
      precursors as much as 7- to 12-fold in a dose-dependent manner. IgG2a accelerates
      macrophage mannose-receptor expression by several days during in vitro bone
      marrow differentiation; however, treated and control cells ultimately express
      equivalent levels of receptor. Moreover, the effect is independent of cell cycle
      or ambient levels of colony-stimulating factor 1. The coinduction of another
      maturation-dependent lineage-specific antigen, F4/80, and the fact that
      macrophage precursors respond to IgG2a only within the first day of culture,
      indicate that the targeted cell is an early myelomonocytic precursor, responsive
      only during a short, early developmental window. The effect is specific for
      immunoglobulin molecules of the IgG2a and IgG2b subclasses and probably involves
      an Fc gamma-receptor signal-transduction pathway but not macrophage priming or
      activation. Most importantly, a paracrine mechanism of immunoglobulin-mediated
      bone-marrow macrophage differentiation is suggested by experiments in which basal
      levels of mannose-receptor expression are reduced by continual removal of B-cell
      generated IgG from marrow cultures. Thus, IgG2a and IgG2b prompt mannose-receptor
      synthesis and bone-marrow macrophage differentiation and may, therefore, play a
      role in the regulation of macrophage differentiation in host defense.

PMID- 2000370
TI  - Dissociation of object and spatial visual processing pathways in human
      extrastriate cortex.
AB  - The existence and neuroanatomical locations of separate extrastriate visual
      pathways for object recognition and spatial localization were investigated in
      healthy young men. Regional cerebral blood flow was measured by positron emission
      tomography and bolus injections of H2(15)O, while subjects performed face
      matching, dot-location matching, or sensorimotor control tasks. Both visual
      matching tasks activated lateral occipital cortex. Face discrimination alone
      activated a region of occipitotemporal cortex that was anterior and inferior to
      the occipital area activated by both tasks. The spatial location task alone
      activated a region of lateral superior parietal cortex. Perisylvian and anterior
      temporal cortices were not activated by either task. These results demonstrate
      the existence of three functionally dissociable regions of human visual
      extrastriate cortex. The ventral and dorsal locations of the regions specialized
      for object recognition and spatial localization, respectively, suggest some
      homology between human and nonhuman primate extrastriate cortex, with
      displacement in human brain, possibly related to the evolution of
      phylogenetically newer cortical areas.

PMID- 2000371
TI  - Human beta-globin locus control region: analysis of the 5' DNase I hypersensitive
      site HS 2 in transgenic mice.
AB  - The human beta-globin locus control region (LCR) is essential for high-level
      expression of human epsilon-, gamma-, and beta-globin genes. Developmentally
      stable DNase I hypersensitive sites (designated HS) mark sequences within this
      region that are important for LCR activity. A 1.9-kilobase (kb) fragment
      containing the 5' HS 2 site enhances human beta-globin gene expression 100-fold
      in transgenic mice and also confers position-independent expression. To further
      define important sequences within this region, deletion mutations of the 1.9-kb
      fragment were introduced upstream of the human beta-globin gene, and the
      constructs were tested for activity in transgenic mice. Although enhancer
      activity was gradually lost with deletions of both 5' and 3' sequences, a 373
      base-pair (bp) fragment retained the ability to confer relative position
      independent expression. Three prominent DNase I footprints were observed in this
      region with extracts from the human erythroleukemia cell line K-562, one of which
      contained duplicated binding sites for transcription factor AP-1 (activator
      protein 1). When the 1.9-kb fragment containing an 18-bp deletion of the AP-1
      binding sites was tested in transgenic mice, enhancer activity decreased 20-fold
      but position-independent expression was retained.

PMID- 2000372
TI  - Role of integration host factor in the regulation of the glnHp2 promoter of
      Escherichia coli.
AB  - The glnHPQ operon of Escherichia coli encodes components of the high-affinity
      glutamine transport system. One of the two promoters of this operon, glnHp2, is
      responsible for expression of the operon under nitrogen-limiting conditions. The
      general nitrogen regulatory protein (NRI) binds to two overlapping sites centered
      at -109 and -122 from the transcription start site and, when phosphorylated,
      activates transcription of glnHp2 by catalyzing isomerization of the closed sigma
      54-RNA polymerase promoter complex to an open complex. The DNA-bending protein
      integration host factor (IHF) binds to a site immediately upstream of glnHp2 and
      enhances the activation of open complex formation by NRI phosphate. The NRI
      binding sites can be moved several hundred base pairs further upstream without
      altering the ability of NRI phosphate to activate open complex formation. We
      propose that the IHF-induced bend can facilitate or obstruct the interaction
      between NRI phosphate and the closed complex depending on the relative positions
      of NRI phosphate and sigma 54-RNA polymerase on the DNA.

PMID- 2000373
TI  - Complementation of a yeast cell cycle mutant by an alfalfa cDNA encoding a
      protein kinase homologous to p34cdc2.
AB  - The cdc2 protein kinase plays a central role in control of the eukaryotic cell
      cycle of animals and yeasts. We have isolated a cDNA clone (cdc2Ms) from alfalfa
      (Medicago sativa L.) that is homologous to the yeast cdc2/CDC28 genes. The
      encoded protein is 64% identical to the yeast and mammalian counterparts and
      shows all the prominent structural features known from these organisms. Antibody
      raised against a 16-amino acid synthetic peptide with crossreactivity against p34
      proteins recognized a 34-kilodalton protein in extracts of alfalfa cells. When
      transferred into a fission yeast, the plant cdc2 homolog can complement a
      temperature-sensitive cdc2 mutant. Northern analysis revealed higher transcript
      levels in shoots and suspension cultures than in roots. In addition to the
      dominant transcript of 1.4 kilobases detected in the poly(A)+fraction, 2.5- and
      1.2-kilobase transcripts were detected in total RNA preparations from shoots or
      somatic embryos. Suspension cultures that were induced to form somatic embryos by
      an auxin (2,4-dichlorophenoxyacetic acid) showed fluctuations in transcription
      pattern during the induction period and embryogenesis.

PMID- 2000374
TI  - ToxR regulates the production of lipoproteins and the expression of serum
      resistance in Vibrio cholerae.
AB  - The genes encoding three lipoproteins of Vibrio cholerae were identified by a
      combination of DNA sequence analysis and [3H]palmitate labeling of hybrid
      proteins encoded by TnphoA gene fusions. The expression of these three
      lipoproteins, TagA, AcfD, and TcpC, was controlled by ToxR, the cholera toxin
      transcriptional activator. The involvement of other bacterial lipoproteins in
      conferring resistance to the bactericidal effects of complement prompted us to
      examine this possibility in V. cholerae. Remarkably, mutations in toxR and tcp
      genes (including tcpC), involved in the biogenesis of the toxin coregulated pili,
      rendered V. cholerae about 10(4)-10(6) times more sensitive to the vibriocidal
      activity of antibody and complement. Since V. cholerae is a noninvasive organism
      and toxR and tcp mutants are highly defective in intestinal colonization in
      animals and humans, these results raise the possibility that resistance to a gut
      associated, "complement-like" bactericidal activity may be a major virulence
      determinant of V. cholerae and other enterobacterial species.

PMID- 2000375
TI  - Ubiquinol-10 protects human low density lipoprotein more efficiently against
      lipid peroxidation than does alpha-tocopherol.
AB  - The temporal disappearance of natural antioxidants associated with human low
      density lipoprotein (LDL) in relation to the appearance of various classes of
      lipid hydroperoxides was investigated under three types of oxidizing conditions.
      Freshly isolated LDL from plasma of healthy subjects was free of detectable
      amounts of lipid hydroperoxides as measured by HPLC postcolumn chemiluminescence
      detection. Exposure of such LDL to a mild, constant flux of aqueous peroxyl
      radicals led to rapid and complete oxidation of ubiquinol-10, followed by slower
      partial depletion of lycopene, beta-carotene, and alpha-tocopherol. After an
      initial lag period of complete inhibition of detectable lipid peroxidation,
      formation of hydroperoxides of cholesterol esters, triglycerides, and
      phospholipids was observed. The onset of detectable lipid peroxidation
      corresponded closely with the completion of ubiquinol-10 consumption. However,
      small amounts of ascorbate, present as a contaminant in the LDL preparation,
      rather than ubiquinol-10 itself were responsible for the initial lag period.
      Thus, complete consumption of ubiquinol-10 was preceded by that of ascorbate, and
      exposure of ascorbate-free LDL to aqueous peroxyl radicals resulted in immediate
      formation of detectable amounts of lipid hydroperoxides. The rate of radical
      mediated formation of lipid hydroperoxides in ascorbate-free LDL was low as long
      as ubiquinol-10 was present, but increased rapidly after its consumption, even
      though more than 80% and 95% of endogenous carotenoids and alpha-tocopherol,
      respectively, were still present. Qualitatively similar results were obtained
      when peroxyl radicals were generated within LDL or when the lipoprotein was
      exposed to oxidants produced by activated human polymorphonuclear leukocytes. LDL
      oxidation was reduced significantly by supplementing the lipoprotein preparation
      with physiological amounts of either ascorbate or ubiquinol-10. Our data show
      that ubiquinol-10 is much more efficient in inhibiting LDL oxidation than either
      lycopene, beta-carotene, or alpha-tocopherol.

PMID- 2000376
TI  - Phosphorylation of the DNA-binding domain of nonhistone high-mobility group I
      protein by cdc2 kinase: reduction of binding affinity.
AB  - Mammalian high-mobility group I nonhistone protein (HMG-I) is a DNA-binding
      chromatin protein that has been demonstrated both in vitro and in vivo to be
      localized to the A + T-rich sequences of DNA. Recently an unusual binding domain
      peptide, "the A.T-hook" motif, that mediates specific interaction of HMG-I with
      the minor groove of DNA in vitro has been described. Inspection of the A.T-hook
      region of the binding domain showed that it matches the consensus sequence for
      phosphorylation by cdc2 kinase. Here we demonstrate that HMG-I is a substrate for
      phosphorylation by purified mammalian cdc2 kinase in vitro. The site of
      phosphorylation by this enzyme is a threonine residue at the amino-terminal end
      of the principal binding-domain region of the protein. Labeling of mitotically
      blocked mouse cells with [32P]phosphate demonstrates that this same threonine
      residue in HMG-I is also preferentially phosphorylated in vivo. Competition
      binding studies show that cdc2 phosphorylation of a synthetic binding-domain
      peptide significantly weakens its interaction with A + T-rich DNA in vitro, and a
      similar weakening of DNA binding has been observed for intact murine HMG-I
      protein phosphorylated by the kinase in vitro. These findings indicate that cdc2
      phosphorylation may significantly alter the DNA-binding properties of the HMG-I
      proteins. Because many cdc2 substrates are DNA-binding proteins, these results
      further suggest that alteration of the DNA-binding affinity of a variety of
      proteins is an important general component of the mechanism by which cdc2 kinase
      regulates cell cycle progression.

PMID- 2000377
TI  - Isolation and characterization of yeast artificial chromosome clones linking the
      HLA-B and HLA-C loci.
AB  - A 290-kilobase-pair chromosomal segment containing the genes encoding the human
      class I major histocompatibility complex molecules HLA-B and HLA-C as well as a
      class I pseudogene has been isolated on three overlapping yeast artificial
      chromosome (YAC) clones. One YAC clone contains both the HLA-B and HLA-C genes.
      These loci are located approximately 85 kilobase pairs apart, each in close
      association with a CpG island. Southern blotting and nucleotide sequencing showed
      no evidence of alteration of the structure of the cloned DNA in the YACs. End
      fragments from the YAC inserts have been isolated and used to confirm the
      overlaps between clones. These fragments can also serve as polymorphic markers
      for structural analysis of the major histocompatibility complex. Our data show
      that YAC cloning offers an attractive alternative for analysis of the structures
      of large gene complexes such as HLA.

PMID- 2000378
TI  - Lymphocyte activation induces rapid changes in nuclear and cytoplasmic
      glycoproteins.
AB  - A unique form of nucleoplasmic and cytoplasmic protein glycosylation, O-linked
      GlcNAc, (O-GlcNAc) is present on proteins ranging from those of yeast to man,
      including many chromatin proteins, transcription factors, nuclear pore proteins,
      and certain types of cytoskeletal proteins. In this report we have studied the
      effects of cellular activation on O-GlcNAc-modified proteins, using T lymphocytes
      as a model system. Results indicate that the apparent levels of O-GlcNAc on many
      nuclear proteins increases rapidly after lymphocyte activation, returning to
      control levels after a few hours. In contrast, the apparent levels of O-GlcNAc on
      a distinct population of cytosolic proteins decreases rapidly after cellular
      activation and also returns to control levels after a few hours. These data are
      consistent with the hypothesis that O-GlcNAc is a regulatory modification and
      suggest that O-GlcNAc modification may play an important role in the early stages
      of T-lymphocyte activation.

PMID- 2000379
TI  - Energetics of repacking a protein interior.
AB  - To test whether interactions in the hydrophobic core of a protein can be
      adequately modeled based on the properties of a liquid hydrocarbon, we measured
      the unfolding free energies of the wild-type bacteriophage f1 gene V protein and
      29 mutants with apolar substitutions at positions 35 and 47. Stability changes
      arising from identical mutations at these two buried sites are quite different,
      suggesting that one site is more rigid than the other. Reversals of residues at
      positions 35 and 47 confirm that their environments are distinct. Mutants
      containing weakly polar residues at these two sites suggest that the protein
      interior is more polar than a liquid hydrocarbon. Interactions between residues
      at the two sites appear to be minimal. These observations are compatible with a
      view of protein interiors that incorporates properties of liquid hydrocarbons but
      also includes polar interactions and a site-dependent "packing energy" associated
      with changes in internal structure.

PMID- 2000380
TI  - Cleavage of the membrane precursor for transforming growth factor alpha is a
      regulated process.
AB  - Transforming growth factor alpha (TGF-alpha) is generated by cleavage of a
      membrane-anchored precursor protein, proTGF-alpha. ProTGF-alpha is cleaved at a
      slow rate and accumulates on the cell surface, thereby mediating cell-cell
      adhesion and mitogenic stimulation. We show here that cleavage of membrane proTGF
      alpha by an elastase-like enzyme constitutes an important regulatory step in the
      generation of soluble TGF-alpha. Cleavage is activated in response to serum
      factors and tumor-promoting phorbol esters, leading to depletion of cell surface
      proTGF-alpha, which disperses as soluble factor. Activation of proTGF-alpha
      cleavage is mediated by protein kinase C-dependent and -independent mechanisms.
      The results demonstrate the existence of mechanisms that control the switch of
      TGF-alpha from a juxtacrine to a paracrine growth factor.

PMID- 2000381
TI  - Expression of v-src in a murine T-cell hybridoma results in constitutive T-cell
      receptor phosphorylation and interleukin 2 production.
AB  - Ligand binding to the T-cell antigen receptor results in phosphatidylinositol
      hydrolysis and the resultant activation of protein kinase C, as well as the
      activation of a receptor-coupled protein-tyrosine kinase. As a model for tyrosine
      kinase activation in T cells, we used retroviral gene transfer to express the v
      src oncogene in an antigen-specific murine T-cell hybridoma. Clones that
      expressed v-src mRNA demonstrated constitutive tyrosine phosphorylation of
      several cellular substrates, including the zeta chain of the T-cell receptor, and
      constitutive interleukin 2 production. Thus, expression of a constitutively
      active protein-tyrosine kinase such as pp60v-src appears to be sufficient to
      induce the expression of at least one gene critical to the process of T-cell
      activation.

PMID- 2000382
TI  - A serum heterodimer from hagfish (Eptatretus stoutii) exhibits structural
      similarity and partial sequence identity with immunoglobulin.
AB  - We have isolated, characterized, and partially sequenced immunoglobulin from the
      most primitive extant nonvertebrate craniate, the hagfish, a jawless fish that
      may have diverged from the vertebrate lineage more than 500 million years ago.
      The 160-kDa protein, which is a minor serum component, is composed of two
      different heavy chains of 69 and 74 kDa and a light chain of 29 kDa and resembles
      known immunoglobulin on the basis of an equimolar ratio of heavy and light
      chains, N-linked glycosylation of heavy chains, presence of intra- and interchain
      disulfide bonds, and polydispersity of each peptide chain. High molecular mass
      (polymeric) as well as low molecular mass (monomeric) forms were isolated from
      serum. The hagfish immunoglobulin is unique in that each heterodimer is composed
      of two different heavy chains and two light chains. The partial peptide maps and
      amino acid compositions of the two heavy chains differ; the chains do not
      crossreact immunologically. Slight crossreactivity of the 74-kDa heavy chain with
      antisera against purified shark immunoglobulin and some conservation of amino
      acid sequences, including those surrounding a cysteine, suggest that the isolated
      protein is an immunoglobulin.

PMID- 2000383
TI  - Structural diversity in the Plasmodium falciparum merozoite surface antigen 2.
AB  - Antigens associated with the surface of merozoites of the malaria parasite
      Plasmodium falciparum are directly accessible to immune attack and therefore are
      prime vaccine candidates. We have previously shown that one of the two known
      merozoite surface antigens (merozoite surface antigen 2; MSA-2) exhibits
      considerable sequence and antigenic diversity in different isolates. The
      sequences of MSA-2 from three isolates revealed a central domain composed of
      repeats that vary in number, length, and sequence, flanked in turn by
      nonrepetitive variable sequences and by conserved N- and C-terminal domains. We
      report here the sequences of a further four MSA-2 alleles, containing repetitive
      sequences that are related but not identical to each other. The seven alleles of
      MSA-2 can be divided into two distinct allele families on the basis of
      nonrepetitive sequences. Hybridization studies with repeat probes indicated that
      all of the 44 P. falciparum isolates examined contained repeat regions similar to
      those defined in known MSA-2 sequences.

PMID- 2000384
TI  - Heme inhibits human immunodeficiency virus 1 replication in cell cultures and
      enhances the antiviral effect of zidovudine.
AB  - The effects of heme alone and heme administered together with 3'-azido-3'
      deoxythymidine (AZT) on human immunodeficiency virus replication in human
      peripheral blood lymphocytes and in the H9 cell line were studied. Heme enhanced
      the antiviral action of AZT against both drug-resistant and drug-sensitive viral
      strains; the heme effect was more pronounced against the latter. Moreover, heme
      alone displayed a significant ability to inhibit viral replication in
      concentrations markedly smaller than those required to inhibit the reverse
      transcriptase of Rauscher murine leukemia virus. The results of this study extend
      the range of pharmacological actions that metalloporphyrins exert in biological
      systems and suggest that further study of the interactions of the natural
      compound heme and human immunodeficiency virus chemotherapeutic agents such as
      AZT may be useful.

PMID- 2000385
TI  - Nerve growth factor corrects developmental impairments of basal forebrain
      cholinergic neurons in the trisomy 16 mouse.
AB  - The trisomy 16 (Ts16) mouse, which shares genetic and phenotypic homologies with
      Down syndrome, exhibits impaired development of the basal forebrain cholinergic
      system. Basal forebrains obtained from Ts16 and euploid littermate fetuses at 15
      days of gestation were dissociated and cultured in completely defined medium,
      with cholinergic neurons identified by choline acetyltransferase (ChAT)
      immunoreactivity. The Ts16 cultures exhibited fewer ChAT-immunoreactive neurons,
      which were smaller and emitted shorter, smoother, and more simplified neurites
      than those from euploid littermates. Whereas the addition of beta-nerve growth
      factor (100 ng/ml) augmented the specific activity of ChAT and neuritic extension
      for both Ts16 and euploid cholinergic neurons, only Ts16 cultures exhibited an
      increase in the number and size of ChAT-immunoreactive neurons. Furthermore, Ts16
      ChAT-immunoreactive neurites formed varicosities only in the presence of beta
      nerve growth factor.

PMID- 2000386
TI  - Tunicamycin increases desensitization of acetylcholine receptors in cultured
      mouse muscle cells.
AB  - Whole-cell currents activated by acetylcholine (AcCho) were recorded in C2 mouse
      myotubes before and after prolonged treatment with tunicamycin, an inhibitor of
      glycosylation. In control cells the AcCho-induced currents decayed slowly even in
      the continuous presence of AcCho. After 24 hr of treatment with tunicamycin AcCho
      still elicited currents, but their size was significantly reduced and their decay
      was greatly accelerated. The binding of 125I-labeled alpha-bungarotoxin, a
      specific and irreversible antagonist of muscle AcCho receptors, was greatly
      reduced after tunicamycin treatment, and an equivalent reduction was observed
      after a long-lasting application of the AcCho agonist carbachol. We suggest that,
      after inhibition of glycosylation by tunicamycin, AcCho receptors are expressed
      correctly on the plasma membrane but these receptors desensitize more rapidly and
      are less efficient in binding alpha-bungarotoxin.

PMID- 2000387
TI  - The speed of attentional shifts in the visual field.
AB  - The scanning speed of focal visual attention was measured directly by flashing a
      sequence of two, three, or four numerals one by one at random retinal positions
      and at a distance from each other to avoid interference between the numerals.
      Each numeral was followed by a mask pattern so the observers had to move their
      focal attention in the visual field in synchrony and at the same speed as the
      presentation rate of the numerals in order to recognize every numeral in the
      stimulus sequence. Observers could recognize the numerals orders of magnitude
      above the theoretical chance level of performance even when the presentation rate
      was as fast as 33 ms per numeral. However, the temporal order of the numerals was
      perceived rather poorly at the fast presentation rates and for the sequences of
      four numerals.

PMID- 2000388
TI  - An Id-related helix-loop-helix protein encoded by a growth factor-inducible gene.
AB  - An mRNA encoding a helix-loop-helix protein that we have named HLH462 is induced
      in mouse 3T3 cells as part of the immediate early transcriptional response to
      growth factors and other signaling agents. The RNA is present in a number of
      mouse tissues and in the developing mouse fetus. The HLH462 gene has been mapped
      by interspecific backcross analysis to the distal region of mouse chromosome 4.
      In its helix-loop-helix region HLH462 is closely related to the Id protein and
      the Drosophila emc protein. Like Id, HLH462 lacks a basic region required for DNA
      binding, and it inhibits the DNA-binding activities of other helix-loop-helix
      proteins. On the basis of its structural and functional similarity to Id, we
      suggest that HLH462 may inhibit the activities of helix-loop-helix transcription
      factors during the cellular growth response and during development.

PMID- 2000389
TI  - Comparison of cloned genes provides evidence for intergenomic exchange of DNA in
      the evolution of a tobacco glucan endo-1,3-beta-glucosidase gene family.
AB  - Two genes for prepro glucan endo-1,3-beta-glucosidase (1,3-beta-glucanase; 1,3
      beta-D-glucan glucanohydrolase, EC 3.2.1.39) of tobacco were cloned and their
      sequences were compared with cDNA clones. Southern analysis indicates that the
      genomic clones represent genes derived from ancestral parents of tobacco similar
      to the present day species Nicotiana sylvestris and Nicotiana tomentosiformis,
      whereas the genes represented by two of the cDNA clones appear to be unique to
      tobacco. The coding sequences of the genomic clones and cDNA clones differed at
      less than 2.2% of the positions, indicating that the tobacco 1,3-beta-glucanase
      gene family is highly conserved. Alternating blocks of sequence in the cDNA
      clones were identical to the coding sequence of the two genomic clones. These
      results and an analysis of evolutionary distances for nucleotide substitution are
      consistent with the hypothesis that the evolution of the tobacco 1,3-beta
      glucanase gene family has involved exchange of DNA between members of the
      tomentosiformis and sylvestris subgenomes by recombination or gene conversion.

PMID- 2000390
TI  - Stage transitions in B-lymphocyte differentiation correlate with limited
      variations in nuclear proteins.
AB  - Total nuclear proteins extracted from cell lines representing various stages of
      differentiation of mouse B lymphocytes were studied by computer analysis of two
      dimensional gels. Of the 1438 spots present on the gels, 55 varied significantly
      in intensity during differentiation. The variations occurred most often in steps
      correlating with those classically defined for B-cell differentiation. Seventeen
      spots were not detectable in at least one of the stages (qualitative variations)
      and could represent switching on or off of genes coding for nuclear proteins.
      Detailed analysis of the 55 variable spots showed that they fall into small sets
      characterized by similar expression profiles, which argues for a combinatorial,
      multistep control mechanism of gene expression. In addition, analysis of the
      expression of all the nuclear proteins resolved on the gels clearly
      differentiated B-lineage cells from myeloid cells and suggested that the most
      important transition in B-cell differentiation occurs between the resting B cell
      and plasmocyte stages.

PMID- 2000391
TI  - Chromosome microdissection and cloning in human genome and genetic disease
      analysis.
AB  - A procedure has been described for microdissection and microcloning of human
      chromosomal DNA sequences in which universal amplification of the dissected
      fragments by Mbo I linker adaptor and polymerase chain reaction is used. A very
      large library comprising 700,000 recombinant plasmid microclones from 30
      dissected chromosomes of human chromosome 21 was constructed. Colony
      hybridization showed that 42% of the clones contained repetitive sequences and
      58% contained single or low-copy sequences. The insert sizes generated by
      complete Mbo I cleavage ranged from 50 to 1100 base pairs with a mean of 416 base
      pairs. Southern blot analysis of microclones from the library confirmed their
      human origin and chromosome 21 specificity. Some of these clones have also been
      regionally mapped to specific sites of chromosome 21 by using a regional mapping
      panel of cell hybrids. This chromosome microtechnology can generate large numbers
      of microclones with unique sequences from defined chromosomal regions and can be
      used for processes such as (i) isolating corresponding yeast artificial
      chromosome clones with large inserts, (ii) screening various cDNA libraries for
      isolating expressed sequences, and (iii) constructing region-specific libraries
      of the entire human genome. The studies described here demonstrate the power of
      this technology for high-resolution genome analysis and explicate their use in an
      efficient search for disease-associated genes localized to specific chromosomal
      regions.

PMID- 2000392
TI  - Primary structure of the 170-kDa surface lectin of pathogenic Entamoeba
      histolytica.
AB  - The adherence of Entamoeba histolytica to colonic mucins and to host cells
      appears to be predominantly mediated by a 170-kDa surface lectin of the amoebae.
      By using an antiserum to the purified lectin, the corresponding cDNA was isolated
      from an expression library of the pathogenic E. histolytica isolate HM-1:IMSS.
      Northern blot analysis indicated a transcript of approximately 4 kilobases, and
      Southern blot analyses suggested that multiple genes may encode the lectin or
      closely related proteins in HM-1:IMSS trophozoites. The cDNA-deduced amino acid
      sequence revealed an N-terminal signal peptide and a mature protein of 1270 amino
      acids corresponding to a molecular mass of 143 kDa, which comprises a short C
      terminal cytoplasmic domain with potential phosphorylation sites, a transmembrane
      region, and a large extracellular portion with nine potential asparagine-linked
      glycosylation sites. The extracellular portion may be separated into a cysteine
      poor domain and a cysteine-rich domain, the latter of which shows in part
      repetitive structural elements with a low degree of sequence homology to wheat
      germ agglutinin and to pDd63, a developmentally expressed protein of
      Dictyostelium discoideum.

PMID- 2000393
TI  - Expressions of the low density lipoprotein receptor and 3-hydroxy-3
      methylglutaryl coenzyme A reductase genes are stimulated by recombinant platelet
      derived growth factor isomers.
AB  - The plausible role that platelet-derived growth factor (PDGF) has in the
      localized pathophysiological changes that occur in the arterial wall during
      development of atherosclerotic lesions led us to investigate the influence of
      recombinant (r)PDGF isomers -AA, -AB, and -BB on the expression of low density
      lipoprotein receptor (LDL-R) and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)
      reductase [(S)-mevalonate:NAD+ oxidoreductase (CoA-acylating), EC 1.1.1.88]
      genes. In addition, we clarified the role of protein kinase C (PKC) in expression
      of the two genes in human skin fibroblasts and vascular smooth muscle cells. The
      various rPDGF isoforms are distinct in their ability to activate transcription of
      both genes: (i) Both rPDGF-AA and -BB stimulate transcription of the LDL-R gene;
      in contrast, rPDGF-BB, but not -AA, activates transcription of the HMG-CoA
      reductase gene. (ii) All recombinant isoforms of PDGF activate transcription of
      the c-fos gene. (iii) While rPDGF-dependent transcription of the LDL-R gene
      occurs independently of PKC, transcription of the HMG-CoA reductase gene appears
      to involve the action of that enzyme.

PMID- 2000394
TI  - Human cyclophilin B: a second cyclophilin gene encodes a peptidyl-prolyl
      isomerase with a signal sequence.
AB  - We report the cloning and characterization of a cDNA encoding a second human
      cyclosporin A-binding protein (hCyPB). Homology analyses reveal that hCyPB is a
      member of the cyclophilin B (CyPB) family, which includes yeast CyPB, Drosophila
      nina A, and rat cyclophilin-like protein. This family is distinguished from the
      cyclophilin A (CyPA) family by the presence of endoplasmic reticulum (ER)
      directed signal sequences. hCyPB has a hydrophobic leader sequence not found in
      hCyPA, and its first 25 amino acids are removed upon expression in Escherichia
      coli. Moreover, we show that hCyPB is a peptidyl-prolyl cis-trans isomerase which
      can be inhibited by cyclosporin A. These observations suggest that other members
      of the CyPB family will have similar enzymatic properties. Sequence comparisons
      of the CyPB proteins show a central, 165-amino acid peptidyl-prolyl isomerase and
      cyclosporin A-binding domain, flanked by variable N-terminal and C-terminal
      domains. These two variable regions may impart compartmental specificity and
      regulation to this family of cyclophilin proteins containing the conserved core
      domain. Northern blot analyses show that hCyPB mRNA is expressed in the Jurkat T
      cell line, consistent with its possible target role in cyclosporin A-mediated
      immunosuppression.

PMID- 2000395
TI  - Glutathione deficiency leads to mitochondrial damage in brain.
AB  - Glutathione deficiency induced in newborn rats by giving buthionine sulfoximine,
      a selective inhibitor of gamma-glutamylcysteine synthetase, led to markedly
      decreased cerebral cortex glutathione levels and striking enlargement and
      degeneration of the mitochondria. These effects were prevented by giving
      glutathione monoethyl ester, which relieved the glutathione deficiency, but such
      effects were not prevented by giving glutathione, indicating that glutathione is
      not appreciably taken up by the cerebral cortex. Some of the oxygen used by
      mitochondria is known to be converted to hydrogen peroxide. We suggest that in
      glutathione deficiency, hydrogen peroxide accumulates and damages mitochondria.
      Glutathione, thus, has an essential function in mitochondria under normal
      physiological conditions. Observations on turnover and utilization of brain
      glutathione in newborn, preweaning, and adult rats show that (i) some glutathione
      turns over rapidly (t 1/2, approximately 30 min in adults, approximately 8 min in
      newborns), (ii) several pools of glutathione probably exist, and (iii) brain
      utilizes plasma glutathione, probably by gamma-glutamyl transpeptidase-initiated
      pathways that account for some, but not all, of the turnover; thus, there is
      recovery or transport of cysteine moieties. These studies provide an animal model
      for the human diseases involving glutathione deficiency and are relevant to
      oxidative phenomena that occur in the newborn.

PMID- 2000396
TI  - Signals for retention of transmembrane proteins in the endoplasmic reticulum
      studied with CD4 truncation mutants.
AB  - A mutant of CD4 (CD4.Q421stop), in which the cytoplasmic C-terminal 13 amino
      acids were truncated, was not expressed on the surface of HeLa cells after
      transfection but was retained in the endoplasmic reticulum (ER). Seven other
      truncation mutants of CD4 were expressed well on the cell surface, thus
      suggesting that the C-terminal amino acids of CD4.Q421stop (-Ser-Glu-Lys-Lys-Thr
      Cys) may have the sequence information for ER retention. Further mutational study
      has revealed that two consecutive lysine residues at the third and fourth
      positions from the C-terminal end are sufficient for ER retention. Lysine at the
      fourth position, but not at the third position, from the C terminus can be
      replaced by arginine without disturbing ER retention. Furthermore, two lysine
      residues at the third and fifth positions from the C terminus also resulted in ER
      retention. Thus lysine at the third position and a positively charged amino acid
      either at the fourth or fifth position from the C terminus are sufficient for ER
      retention of this CD4 mutant, and possibly all transmembrane proteins. In
      addition to the requirement of specific amino acids at specific positions, the ER
      retention signal -Lys-Lys-Xaa-Xaa also requires a transmembrane region for
      function. By contrast -Lys-Asp-Glu-Leu, which targets soluble proteins to the
      lumen of the ER, does not function in the presence of a transmembrane region.

PMID- 2000397
TI  - Canonical ordered cosmid library of the symbiotic plasmid of Rhizobium species
      NGR234.
AB  - Many of the bacterial genes involved in nodulation (nod) and nitrogen fixation
      (nif) are dispersed over the 500-kilobase plasmid pNGR234a of the broad host
      range Rhizobium species NGR234. As a first step toward generating a complete
      physical and genetic map of the plasmid, a full overlapping collection of cosmids
      was derived from a total genomic library. Clones were aligned by combining
      fingerprinting, hybridization, and pulsed-field gel electrophoresis data.
      Symbiotic loci were localized by probing a representative set of cosmids with
      both homologous and heterologous genes. nodABC, nodD1, nodD2, nodSU, nolB, and
      region II are widely dispersed over pNGR234a, while the two functional copies of
      nifKDH are separated by only 28 kilobases. Interestingly, sequences homologous to
      nodE, nodG, nodP, and nodQ have been assigned to another autonomously replicating
      element in Rhizobium species NGR234. Similarly one copy of the structural dctA
      gene is located on the symbiotic plasmid (dctA1) while the other is on what we
      assume to be the chromosome.

PMID- 2000398
TI  - Angiotensin II induces secretion of plasminogen activator inhibitor 1 and a
      tissue metalloprotease inhibitor-related protein from rat brain astrocytes.
AB  - The present study investigates angiotensin (Ang) II effects on secretory protein
      synthesis in brain astrocytes cultured from neonatal and 21-day-old rats. Ang II
      induced changes in the de novo synthesis of [35S]methionine-labeled secretory
      proteins were visualized using two-dimensional NaDodSO4/PAGE. Astrocytes from 21
      day-old rat brain possess specific high-affinity receptors for Ang II. These
      cells express two Ang II-induced secretory proteins with Mr 55,000 (AISP-55K) and
      Mr 30,000 (AISP-30K), which were time- and dose-dependent (EC50, 1 nM). [Sar1,
      Ile8]Ang II (where Sar is sarcosine) inhibited Ang II-induced secretion of AISP
      55K but not AISP-30K. N-terminal amino acid sequencing indicates that AISP-55K is
      identical to rat plasminogen activator inhibitor 1, whereas AISP-30K exhibits 72
      81% identity to three closely related proteins: human tissue inhibitor of
      metalloproteases, a rat phorbol ester-induced protein, and the murine growth
      responsive protein 16C8. Immunofluorescent staining with rat plasminogen
      activator inhibitor 1 antibody was induced in the majority of cells in culture
      after Ang II treatment of astrocytes from 21-day-old rat brains. Absence of this
      response to Ang II in astrocytes from neonatal rat brain provides evidence that
      this action of Ang II on astrocytes is developmentally regulated.

PMID- 2000400
TI  - A cDNA encoding a human CCAAT-binding protein cloned by functional
      complementation in yeast.
AB  - We constructed a comprehensive cDNA library from HeLa cell mRNA in a vector that
      directs expression of the cDNA in Saccharomyces cerevisiae. We used this library
      to clone the human counterpart of the Sa. cerevisiae CCAAT-binding transcription
      factor, Hap2, by functional complementation of a hap2 mutation. The cDNA encoding
      the human Hap2 homolog encodes a protein of 257 amino acids that has a 62-amino
      acid carboxyl-terminal region 73% identical to the essential core region of Hap2.
      The amino terminus of the protein is highly enriched in glutamine residues,
      reminiscent of transcriptional activation domains of several other mammalian
      transcription factors. Analysis of human Hap2 expression reveals three major
      transcripts: a 4.1-kilobase species found in all cell types examined, a 7.0
      kilobase species specific to B lymphocytes, and a 1.6-kilobase species that is
      expressed preferentially in HeLa cells and that likely corresponds to our cDNA
      clone. Thus, the human Hap2 homolog and related factors may play both a
      constitutive and cell type-specific role in gene expression. The general approach
      of cloning by complementation should allow the isolation of many human genes for
      which corresponding yeast mutations exist.

PMID- 2000399
TI  - Long-chain (sphingoid) bases inhibit multistage carcinogenesis in mouse
      C3H/10T1/2 cells treated with radiation and phorbol 12-myristate 13-acetate.
AB  - Sphingosine and other long-chain (sphingoid) bases inhibit protein kinase C, the
      putative cellular receptor for the tumor promoter phorbol 12-myristate 13-acetate
      (PMA), and exert potent effects on diverse cell functions. We tested the ability
      of long-chain bases to modulate multistage carcinogenesis in mouse C3H/10T1/2
      cells exposed to gamma-rays and PMA. Sphingosine and sphinganine completely
      blocked the enhancement of radiation-induced transformation by PMA (promotion)
      and partially suppressed transformation by radiation alone. N-Acetylsphingosine,
      a ceramide analog, did not inhibit transformation. Sphingosine was rapidly taken
      up by the cells and metabolized; hence, the long-chain bases were added daily to
      achieve prolonged inhibition. Long-chain bases inhibited protein kinase C
      activity in C3H/10T1/2 cells and suppressed the down-regulation of this enzyme by
      PMA. Our results establish that long-chain bases are highly effective inhibitors
      of carcinogenesis in this model. Our results also indicate that the suppressive
      effects may be mediated, in part, by inhibition of protein kinase C. The data
      suggest that sphingosine and other long-chain bases derived from complex
      sphingolipids may act as cancer-preventative agents.

PMID- 2000401
TI  - The pharmacophore of debromoaplysiatoxin responsible for protein kinase C
      activation.
AB  - Protein kinase C is physiologically activated by 1,2-diacyl-sn-glycerol in the S
      configuration. The enzyme is also powerfully activated by structurally diverse
      tumor promotors. A model has been developed that demonstrates how the various
      tumor promotors and diacylglycerols can all be accommodated by the same binding
      site of the kinase. One prediction of this model concerns the structural nature
      of the pharmacophore in the tumor promotor debromoaplysiatoxin. This prediction
      is realized by synthesizing the analogs with the deduced pharmacophore and
      demonstrating that they are potent activators of protein kinase C. These findings
      provide strong experimental support for our structural model of protein kinase C
      activation.

PMID- 2000402
TI  - Interstrand cross-links are preferentially formed at the d(GC) sites in the
      reaction between cis-diamminedichloroplatinum (II) and DNA.
AB  - A DNA restriction fragment with convergent SP6 and T7 promoters has undergone
      reaction with cis-diamminedichloroplatinum(II) (cis-DDP) and was then used as a
      template for RNA synthesis in vitro. The T7 and SP6 RNA polymerases generate
      fragments of defined sizes. Analysis of the RNA fragments shows that the
      polymerases are mainly blocked at the level of the d(GG) and d(AG) sites and to a
      lesser extent at the level of the d(GC) sites. The adducts at the d(GC) sites are
      more resistant to cyanide ion attack than those at the major sites and are
      identified as interstrand cross-links. The formation of an interstrand cross-link
      between the N-7 atoms of two guanine residues at the d(GC) sites was further
      confirmed by chemical modifications.

PMID- 2000403
TI  - Glycosylation site-binding protein is not required for N-linked glycoprotein
      synthesis.
AB  - In prior studies we identified a 57-kDa protein in the lumen of the endoplasmic
      reticulum that, in addition to having both protein disulfide isomerase and
      thyroid hormone-binding protein activities, bound a photoaffinity probe
      containing the N-glycosylation-site sequence Asn-Xaa-Ser/Thr. It was hypothesized
      that this multifunctional protein, called glycosylation site-binding protein
      (GSBP), participated in the process of N-glycosylation of proteins. To test this
      hypothesis we have employed various conditions to deplete the lumen of GSBP and
      then assess the level of N-glycosylation catalyzed by oligosaccharyltransferase
      (OTase). Although most conditions leading to depletion resulted in partial loss
      of OTase activity, this loss was independent of the extent of GSBP depletion.
      Indeed, virtually complete loss (greater than 99%) of GSBP with partial retention
      of OTase activity was frequently observed. Moreover, repletion of the microsomal
      lumen with GSBP did not restore OTase activity to control levels. Thus, no
      correlation between GSBP content and OTase activity before or after
      reconstitution was found. These results suggest that this multifunctional 57-kDa
      protein is not an essential component of the enzymatic reaction in which
      oligosaccharide chains are transferred from dolichyl-P-P-GlcNAc2Man9Glc3 to
      nascent polypeptides or to synthetic tripeptide acceptors.

PMID- 2000404
TI  - Direct evidence that ganglioside is an integral component of the thyrotropin
      receptor.
AB  - Gangliosides were extracted from purified human and porcine thyrotropin (TSH)
      receptors (TSH-R) and were detected by probing with an 125I-labeled sialic acid
      specific lectin, Limax flavus agglutinin. Gangliosides copurified with human and
      porcine TSH-R migrated between monosialoganglioside GM1 and disialoganglioside
      GD1a. Ceramide glycanase digestion of the purified human TSH-R-associated
      glycolipid confirmed its ganglioside nature. It was resistant to Vibrio cholerae
      sialidase, which digests all gangliosides except GM1, but was sensitive to
      Arthrobacter ureafaciens sialidase, which digests all gangliosides including GM1.
      These findings indicate that the human TSH-R contains ganglioside that belongs to
      the galactosyl(beta 1----3)-N-acetylgalactosaminyl (beta 1----4)-[N
      acetylneuraminyl(alpha 2----3)]galactosyl(beta 1----4) glucosyl(beta 1---
      1)ceramide (GM1) family. Its intimate association with receptor protein implies a
      key role for ganglioside in the structure and function of the TSH-R.

PMID- 2000405
TI  - T-lymphocyte interleukin 2-dependent tyrosine protein kinase signal transduction
      involves the activation of p56lck.
AB  - Addition of interleukin 2 (IL-2) to IL-2-dependent T cells results in tyrosine
      protein kinase signal transduction events even though the IL-2 receptor alpha and
      beta chains lack intrinsic enzymatic activity. Here we report that addition of IL
      2 to IL-2-dependent human T cells transiently stimulates the specific activity of
      p56lck, a member of the src family of nonreceptor tyrosine protein kinases
      expressed at high levels in T lymphocytes. The ability of IL-2 to induce p56lck
      activation was found to be independent of the capacity of p56lck to associate
      with either CD4 or CD8. Following IL-2 treatment, p56lck was found to undergo
      serine/threonine phosphorylation modifications that resulted in altered mobility
      of the lck gene product on polyacrylamide gels. These observations raise the
      possibility that p56lck participates in IL-2-mediated signal transduction events
      in T cells.

PMID- 2000406
TI  - Rabies virus nucleoprotein expressed in and purified from insect cells is
      efficacious as a vaccine.
AB  - A cDNA copy of the RNA gene that encodes the nucleoprotein N of rabies virus
      Evelyn-Rokitnicki-Abelseth strain was cloned into baculovirus. The recombinant
      baculovirus expressed the N protein abundantly in Spodoptera frugiperda cells.
      The N protein was extracted from infected Spodoptera frugiperda cells and
      purified to near homogeneity by affinity chromatography. The purified N protein
      reacted with 31 of 32 monoclonal antibodies that recognize native rabies virus
      ribonucleoprotein. Like the ribonucleoprotein, the purified N protein was a major
      antigen capable of inducing virus-specific helper T cells. Priming of mice with
      the purified N protein prior to a booster inoculation with inactivated Evelyn
      Rokitnicki-Abelseth virus vaccine resulted in a 20-fold increase in the
      production of virus-neutralizing antibodies. After immunization with the purified
      N protein, mice developed a strong anti-ribonucleoprotein antibody response and
      were protected against a lethal challenge of rabies virus. These data indicate
      that the N protein expressed in insect cells is antigenically and immunogenically
      comparable to the authentic rabies virus ribonucleoprotein and therefore
      represents a potential source of an effective and economical vaccine for large
      scale immunization of humans and animals against rabies.

PMID- 2000407
TI  - Molecular characterization of a major nephritogenic domain in the autoantigen of
      anti-tubular basement membrane disease.
AB  - Anti-tubular basement membrane (alpha TBM) disease is a form of primary
      interstitial nephritis mediated by autoimmune T cells and alpha TBM antibodies.
      In mice and humans the nephritogenic immune response is directed to a
      glycoprotein (3M-1) found along the proximal tubule of the kidney. We have
      isolated cDNAs from an expression library that encodes for the common framework
      domain of the 3M-1 antigen. This common domain was once related evolutionarily to
      a family of intermediate filament-associated proteins. Northern hybridization
      revealed that all isoforms of 3M-1 range between 1700 and 1900 base pairs and in
      situ hybridization studies indicate that transcripts are found in tubular
      epithelium. Candidate peptide fragments were deduced and synthesized from the
      sequence encoding this common framework domain, and one of the peptide residues
      was able to bind a monoclonal 3M-1-reactive alpha TBM antibody, stimulate the
      growth of 3M-1-reactive helper T cells, and induce nephritogenic effector T cells
      capable of producing interstitial nephritis. Our results indicate that a unique,
      immunodominant region of the 3M-1 antigen is an informative participant in the
      emergence of autoimmune injury to certain basement membranes.

PMID- 2000408
TI  - Differentiation of HL-60 leukemia by type I regulatory subunit antisense
      oligodeoxynucleotide of cAMP-dependent protein kinase.
AB  - A marked decrease in the type I cAMP-dependent protein kinase regulatory subunit
      (RI alpha) and an increase in the type II protein kinase regulatory subunit (RII
      beta) correlate with growth inhibition and differentiation induced in a variety
      of types of human cancer cells, in vitro and in vivo, by site-selective cAMP
      analogs. To directly determine whether RI alpha is a growth-inducing protein
      essential for neoplastic cell growth, human HL-60 promyelocytic leukemia cells
      were exposed to 21-mer RI alpha antisense oligodeoxynucleotide, and the effects
      on cell replication and differentiation were examined. The RI alpha antisense
      oligomer brought about growth inhibition and monocytic differentiation, bypassing
      the effects of an exogenous cAMP analog. These effects of RI alpha antisense
      oligodeoxynucleotide correlated with a decrease in RI alpha receptor and an
      increase in RII beta receptor level. The growth inhibition and differentiation
      were abolished, however, when these cells were exposed simultaneously to both RI
      alpha and RII beta antisense oligodeoxynucleotides. The RII beta antisense
      oligodeoxynucleotide alone has been previously shown to specifically block the
      differentiation inducible by cAMP analogs. These results provide direct evidence
      that RI alpha cAMP receptor plays a critical role in neoplastic cell growth and
      that cAMP receptor isoforms display specific roles in cAMP regulation of cell
      growth and differentiation.

PMID- 2000409
TI  - Protein kinase C inhibitors prevent induction and continued expression of cell
      memory in Hermissenda type B photoreceptors.
AB  - Injections of cAMP-dependent, Ca2+/calmodulin-dependent, or Ca2+/phospholipid
      dependent protein kinases into Hermissenda crassicornis type B photoreceptors are
      sufficient to induce many of the changes in B-cell excitability produced by
      associative conditioning. We report that inhibitors of Ca2+/phospholipid
      dependent protein kinases, but not inhibitors of cyclic nucleotide- or
      Ca2+/calmodulin-dependent protein kinases, prevent the induction as well as
      continued expression of learning-produced changes in type-B-cell excitability:
      reductions of voltage-dependent and Ca2(+)-activated K+ currents. Our results
      represent a direct demonstration of long-term (days) experientially induced
      modulation of ion-channel activity that is dependent upon persistent kinase
      activity.

PMID- 2000411
TI  - Site and strand specificity of UVB mutagenesis in the SUP4-0 gene of yeast.

PMID- 2000410
TI  - Dipoles localized at helix termini of proteins stabilize charges.
AB  - The charge-stabilization effect associated with alpha-helices in proteins has
      been reexamined by microscopic calculations without any a priori assumptions
      about the dielectric constant of the protein. The calculations reproduce the
      observed charge stabilization effect of a helix in two well-defined test cases: a
      histidine residue situated at the C-terminal end of a helix in barnase and the
      sulfate ligand located near the N-terminal end of a helix of the sulfate-binding
      protein. They also show that the effective dielectric constant for helix-charge
      interactions is much larger than previously assumed and that the stabilizing
      effect of the helix is not associated with the helix macrodipole but rather with
      a few localized dipoles confined mostly to the first turn of the helix. It is
      predicted that mutations at one end of the helix should have very small effects
      on the stabilization of charges at the opposite terminus. It is pointed out that
      the relatively short-ranged effect of the helix is essentially similar to other
      cases in which localized dipoles play key roles in electrostatic stabilization.

PMID- 2000412
TI  - Why is there this great divide?

PMID- 2000413
TI  - Influenza--the seasonal virus.

PMID- 2000414
TI  - A new specialist for nutritional care. The role of the nutrition nurse
      specialist.
AB  - Nutrition nurse specialists play an increasingly important role in the hospital
      nutrition team, responsible for the clinical care of patients on enteral and
      parenteral nutrition and the educational development of nursing colleagues. This,
      the first of an occasional series looking at different nursing specialties,
      examines the work of these nurses.

PMID- 2000415
TI  - Rooting for the source of anxiety. Child psychotherapy at work.
AB  - Child psychotherapists work with a wide range of children suffering from
      emotional and behavioural difficulties. They help children to understand their
      fantasies and feelings, so that they can better manage their lives.

PMID- 2000416
TI  - A policy that protects. The Waterlow Pressure Sore Prevention/Treatment Policy.
AB  - The Waterlow card has been a valuable tool in the assessment and prevention of
      pressure sores. Its use cannot only protect patients from unnecessary sores, but
      also health authorities from legal action.

PMID- 2000417
TI  - A sticky situation? Microbiological study of adhesive tape used to secure i.v.
      cannulae.
AB  - Intravenous cannulae are often secured by adhesive tape. This study looks at the
      infection risk this poses and recommends good practice to protect a vulnerable
      group of patients.

PMID- 2000418
TI  - The dry season. Promoting continence in the South West.
AB  - Effective continence promotion and education must come into the public arena. One
      unit in the South West has worked to provide education and support for both
      people with continence problems and those working with and caring for them.

PMID- 2000419
TI  - A vital barrier against infection. Maintaining skin integrity in patients with
      liver disease.
AB  - Patients with acute or chronic liver disease often suffer from dry, itchy and
      flaky skin. This study compares the effects of soap and aqueous cream in helping
      maintain the skin's integrity.

PMID- 2000420
TI  - Electro-convulsive therapy: informing patient and nurse.
AB  - Although there is still considerable controversy surrounding electro-convulsive
      therapy (ECT), it is widely used in psychiatric hospitals. Good nursing care is
      central to its successful administration, and nurses must be able to explain the
      procedure to patients and why it can help them.

PMID- 2000421
TI  - An effective way to reduce mortality. Screening for malignant breast disease.
AB  - Early detection of breast cancer can enable surgery to save a woman's breast. To
      supplement breast cancer screening programmes, breast self-examination should be
      taught to women who are at risk, reducing an avoidably high mortality rate.

PMID- 2000422
TI  - When expert help is needed.

PMID- 2000423
TI  - PREPP: these responses need more expression.

PMID- 2000424
TI  - The path towards a common goal. Structuring the counselling process.
AB  - Individual counselling requires clear objectives if it is to succeed. By
      structuring the counselling process, both client and therapist can ensure therapy
      caters to specific needs and achieves desired outcomes.

PMID- 2000425
TI  - Will the minimum become an optimum? PREPP: mandatory study leave for nurses.
AB  - This, the first in a series of articles on issues surrounding PREPP, looks at the
      recommendation that nurses complete a minimum of five days study leave every
      three years. The series aims to raise issues to help practitioners focus their
      thoughts before responding to the UKCC.

PMID- 2000426
TI  - A threat to femininity? Minimising side-effects in pelvic irradiation.
AB  - Pelvic irradiation is a source of fear and anxiety for women suffering from
      cancers of the cervix, uterus or ovary. If caught early, the chances of full
      recovery are excellent, and with support and planning the side-effects of
      radiotherapy can be overcome.

PMID- 2000427
TI  - A holistic approach and the ideal dressing. Cavity wound management in the 1990s.
AB  - Nurses must take care that the wide range of wound dressings now available does
      not distract them from patients' holistic needs. Dressings must be applied to
      suit individual requirements.

PMID- 2000428
TI  - In-depth analysis required for opioid postoperative pain relief.

PMID- 2000429
TI  - Credit where credit's due. How to borrow money effectively.
AB  - Neither a borrower or a lender be, says the old proverb. However, used
      effectively, credit can help you to make the most of your money - so long as you
      are careful!

PMID- 2000430
TI  - Nurse, is it ME? Understanding myalgic encephalomyelitis.
AB  - Ignored or dismissed for years, myalgic encephalomyelitis (ME) is now recognised
      as a genuine illness, and sufferers are recommended strict rest until the
      symptoms of the virus subside. Public understanding of ME is still uncertain, and
      nurses are ideally placed to provide practical information and support.

PMID- 2000431
TI  - It's OK having asthma ... young children's beliefs about illness.
AB  - Hospitals and illness can be bewildering and frightening for children. To
      minimise the distress caused to them, health professionals need to communicate
      effectively. This involves assessing the child's level of development and the
      amount of knowledge the child needs.

PMID- 2000432
TI  - A pommy nurse down under.

PMID- 2000433
TI  - Direct access: beyond the diatribes.

PMID- 2000434
TI  - Age-related balance changes in hearing-impaired children.
AB  - This study compared balance skills of hearing-impaired children with those of
      hearing children in order to determine whether a deficit in balance exists in
      hearing-impaired children and to ascertain whether this deficit is age-related.
      Twenty-eight hearing-impaired subjects were chosen as a sample of convenience
      from the Pennsylvania School for the Deaf and placed into one of three age
      groups. Ten subjects were in the 4.5 to 6.5-year-old age group, 8 in the 8- to 10
      year-old age group, and 10 in the 12.5 to 14.5-year-old age group. Selection
      criteria included bilateral sensorineural hearing loss of greater than or equal
      to 65 dB and normal intelligence (IQ greater than or equal to 80). Balance was
      measured by the use of the Balance subtest of the Bruininks-Oseretsky Test of
      Motor Proficiency. For each age group, a z test was used to compare the subjects'
      scores with the Balance subtest standard scores. The results showed that for each
      age group, the mean score for the hearing-impaired children was lower than the
      standard score. Both older groups had significantly higher scores than the
      youngest group, but the mean scores of the older groups were not significantly
      different. No difference between the subjects' balance scores and the Balance
      subtest standard scores was found among the age groups, suggesting that the
      balance deficit was not age-related. Gender differences were not found for
      balance scores.

PMID- 2000435
TI  - Expert decision making in physical therapy--a survey of practitioners.
AB  - Four hundred American and 384 Australian physical therapists, nominated by their
      peers as expert clinicians, were studied to evaluate whether a particular
      cognitive style was prevalent among expert clinicians, to identify preferred
      sources of information for clinical decision making, and to determine the
      similarities and differences between American and Australian therapists. Results
      were based on usable survey responses from 348 American and 290 Australian
      therapists. Eighty-eight percent of the American therapists and 82% of the
      Australian therapists identified themselves as working primarily in general
      practice, orthopedics, or neurology. The physical therapy assessment and
      interviews with the patient were the preferred sources of information in both
      countries. The physician's referral and communications with other health care
      personnel were reported to be of limited value as sources of information by most
      respondents. Overall, both groups responded most positively to the receptive
      style of data gathering and the systematic style of information processing.
      Therapists working primarily with neurologically impaired patients responded most
      positively to the preceptive style of data gathering and the intuitive style of
      information processing. Therapists working primarily with patients with
      orthopedic disorders responded most positively to the systematic style of
      information processing.

PMID- 2000436
TI  - Chronic pain--assessment of orthopedic physical therapists' knowledge and
      attitudes.
AB  - Orthopedic physical therapists' knowledge of pain mechanisms and methods of pain
      management and their attitudes toward working with patients with benign chronic
      pain were studied. A random sample of 500 members of the American Physical
      Therapy Association's Section on Orthopaedics received by mail a 36-item
      questionnaire. Statistical analysis of scores, using frequencies, means, and
      correlations was performed on the 119 (23.8%) usable returns. All but 4% of the
      respondents preferred to work with patients who are not likely to have chronic
      pain. Seventy-two percent believed their entry-level education in pain management
      and theory was very inadequate or less than adequate to deal with an orthopedic
      patient population. Pain knowledge scores were low (35.8 out of 46 points), and
      the scores on positive attitudes toward treating patients with benign chronic
      pain were lower (20.5 out of 36 points). The study suggests specific deficiencies
      in orthopedic physical therapists' knowledge of clinical pain mechanisms and
      management and potentially undesirable attitudes toward treating patients with
      chronic pain.

PMID- 2000437
TI  - Movement analysis--an aid to early diagnosis of cerebral palsy.
AB  - The purpose of this article is to review research related to the use of clinical
      analysis of movement as an aid to the early diagnosis of cerebral palsy. A
      historical perspective of clinical techniques used by physicians and physical
      therapists in the early diagnosis of cerebral palsy will be presented first,
      including recent research findings on clinical signs that were most predictive of
      this movement disorder. Predictive neuromotor behaviors common across several
      recent studies will be highlighted. Future trends in the use of movement
      analysis, including digitized kinematic analysis of term and preterm infants and
      fetal ultrasound techniques, will be discussed as well.

PMID- 2000438
TI  - Implications of a dynamical systems approach to understanding infant kicking
      behavior.
AB  - Implications of the dynamical systems approach to understanding movement
      dysfunction in infants are discussed. Traditional theories of motor development
      attribute changes in movement to the hierarchical maturation of the central
      nervous system. The dynamical systems approach emphasizes that movement self
      organizes as the result of the interaction of the participating subsystems in
      developmental and real time. In this article, I discuss, from the theoretical
      perspective of the dynamical systems approach, the organization of leg movements
      in low- and high-risk preterm and full-term infants, developmental changes in
      movement in low-risk preterm infants from 34 weeks' gestational age to 40 weeks'
      postgestational age, and differences in movement between low-risk preterm infants
      at 40 weeks' postgestational age and full-term infants. Preliminary data on high
      risk preterm infants are presented. Based on these data, the necessity to review
      and reinterpret traditional concepts of motor development is explored.
      Suggestions are offered and questions posed on how the dynamical systems
      perspective may influence the practice of physical therapy in the evaluation, and
      treatment of infants at risk for movement dysfunction.

PMID- 2000440
TI  - Measurement and treatment in cerebral palsy: an argument for a new approach.
AB  - This article describes the need for a shift in our therapeutic strategies for
      patients with cerebral palsy. Changes in functional abilities must be stressed in
      therapy. Coincident with this emphasis must be the development of functional
      assessments to be used when documenting intervention outcomes. Research on
      functional arm movement using kinematic analysis is described for this patient
      group.

PMID- 2000439
TI  - Cognitive strategies during coincident timing tasks.
AB  - Research findings suggest that experience and cognitive strategies contribute to
      successful performance during perceptual-motor tasks. This article critically
      reviews selected literature on the effects of information-processing skills,
      preferred movement time, experience, and task difficulty on performance during
      coincident timing tasks. Theoretical information and research findings are
      discussed, and their applications to clinical practice are considered. Clinical
      recommendations include assessment of coincident timing skills and use of
      functional activities that provide opportunities to explore and dynamically
      interact with the environment.

PMID- 2000441
TI  - Dorsal rhizotomy for children with cerebral palsy: support for concepts of motor
      control.
AB  - The results from selective dorsal rhizotomy research suggest that therapists need
      to question some common clinical assumptions about movement dysfunction. The
      rationale for performing a selective dorsal rhizotomy is based on the clinical
      assumptions that spasticity is the underlying cause of disordered movement and
      that reducing or eliminating the spasticity will improve movement. This article
      reviews the literature related to movement dysfunction, the effects of selective
      dorsal rhizotomy, and the evidence for disordered motor control in children with
      spastic cerebral palsy. Selective dorsal rhizotomy appears to reduce spasticity
      and increase joint range of motion. Abnormal movement patterns, however, persist
      after the spasticity is reduced. Well-coordinated movement patterns are acquired
      slowly and appear to be related to an intense period of physical therapy. I argue
      that these results provide evidence that the presence of spasticity alone is an
      insufficient explanation for abnormal movement patterns. I propose that physical
      therapists redirect their efforts from developing methods for reducing spasticity
      to developing adequate assessment, treatment, and measurement techniques for
      assessing motor control in children with cerebral palsy. I believe we can
      maximize the functional potential of children with cerebral palsy by identifying
      problems related to motor control and applying sound principles of motor learning
      to treatment.

PMID- 2000442
TI  - Identification of human genes involved in repair and tolerance of DNA damage.
AB  - An overview is presented on strategies of cloning mammalian DNA repair genes.
      Complementation of human and rodent repair defects and mutagen hypersensitivities
      by chromosome and DNA mediated gene transfer and mRNA microinjection is
      described, and the features of the cloned human DNA repair genes are summarized.
      It is shown that transfection of repair deficient cell lines with cloned
      bacterial and human genes may give rise to protection from the genotoxic effects
      of mutagens.

PMID- 2000443
TI  - After X-irradiation a transient arrest of L929 cells in G2-phase coincides with a
      rapid elevation of the level of O6-alkylguanine-DNA alkyltransferase.
AB  - Following X-irradiation of exponentially growing L929 cells two major phenomena
      have been observed. First, there was a delay in cell division which can be
      ascribed to the arrest of cells in the G2-phase (G2-block), and, second, the
      cellular content of the O6-alkylguanine-DNA alkyltransferase (AGT) was markedly
      increased. Flow cytometrical DNA-measurements revealed that cells began to
      accumulate in the G2-phase 4 h after irradiation (p.r.) irrespective of the X-ray
      dose, while both the fraction of cells blocked in G2 and the time period the
      cells persisted in G2 increased with the radiation dose. About 24 h past release
      from the G2-block the distribution of cells in the cell cycle was similar to that
      of untreated control cells. In comparison with control cells the AGT content in
      irradiated cells (4 Gy) was highest at about 48 h p.r. (3.4-fold increase). The
      highest ratio of increase in AGT was, however, observed to occur between about 4
      and 13 h p.r. (2.6-fold increase). As shown by flow cytometrical measurements
      using a BrdUrd/DNA double labeling technique, this rapid primary increase in AGT
      coincides very well with the entrance of cells into the G2-phase. This indicates
      that the cellular AGT content in X-irradiated (parental) cells started to exceed
      the basal level at the beginning of the G2-phase, but not before or during the S
      phase. Once the AGT level was elevated it continued to increase for 2 to 3 cell
      doubling times.

PMID- 2000444
TI  - Mossbauer effect study of gamma-irradiated human oxyhemoglobin.
AB  - Preliminary results of the Mossbauer effect study of human adult oxyhemoglobin in
      erythrocytes exposed to gamma-irradiation with doses of approximately 100,
      approximately 300 and approximately 600 kGy are presented. Mossbauer spectra
      measured at 87 K have been analyzed in two ways. At first, to fit these spectra
      we used the four components oxyhemoglobin, deoxyhemoglobin, hemochromes and non
      heme Fe(III) compound which had been obtained earlier from Mossbauer spectra of X
      irradiated oxyhemoglobin by Chevalier et al. (1983). However, this approximation
      was not satisfactory. Then a new model of spectral fitting with five components
      was used. These were oxyhemoglobin, deoxyhemoglobin and components marked 1, 2
      and 3. Using Mossbauer hyperfine parameters of each component the valence/spin
      states of iron ions were determined and possible complexes were considered. The
      most probable compounds for components 1, 2 and 3 were hematin and/or mu
      oxodimers, methemoglobin hydroxide and/or hemichromes, and the high spin Fe(III)
      complex, respectively. Changes of the relative areas of Mossbauer subspectra of
      all components (its content in samples) versus doses were evaluated and the
      presence of the high and low spin aquomethemoglobin was indicated.

PMID- 2000445
TI  - Criteria and techniques for analysing cell survival data.
AB  - Cell survival was studied by analyzing the inactivation probability density
      function and its fundamental parameters. Mean D, variance sigma 2 and mode Dmode
      were evaluated and a set of equations relating these parameters to the usual
      parameters of the multitarget, multihit and linear-quadratic models Do and n,
      alpha and beta, kappa and lambda are reported. The multihit equation used was an
      extension of the usual equation, to allow parameter kappa to assume values that
      are not necessarily integers. In the multitarget curve, the mode of inactivation
      probability density function, proved to be the quasi-threshold dose Dq = Do
      ln(n). Relative variance, degree of asymmetry and degree of peakedness can be
      calculated from the shape parameters n in the multitarget model, kappa in the
      multihit model, and alpha/square root of beta in the linear-quadratic model. From
      an analysis of eight published cell survival sets of data, on C3H10T1/2 cells
      exposed to low LET radiations, it was found that D, sigma, and SF2 are the
      parameters which exhibit the least variation from experiment to experiment and
      the least variation in selecting the range of data available for estimation.

PMID- 2000446
TI  - Theoretical study of W values in hydrocarbon gases.
AB  - The recent measurements by D. Srdoc, B. Obelic, and I. Krajcar Bronic (J. Phys.
      B, 20, 4473-4484, 1987) and by I. Krajcar Bronic, D. Srdoc, and B. Obelic
      (Radiat. Res., 115, 213-222, 1988) revealed nonsmooth, oscillatory variation of
      the W value for low-energy electrons as a function of the number of carbon atoms
      in normal alkanes. This behavior is contrary to what has been expected generally
      and prompted us to undertake the present study. Calculations were carried out
      using the continuous-slowing-down approximation for the degradation spectrum, the
      binary-encounter theory for cross sections, and relevant molecular properties, to
      explain the behavior of the W value. The main contributor to the oscillatory
      variation is the branching ratio for neutral dissociation to ionization of super
      excited states. We also present an interpretation of the trend of the W value in
      the series C2H2, C2H4, and C2H6.

PMID- 2000447
TI  - The influence of age at time of exposure to 226Ra or 239Pu on distribution,
      retention, postinjection survival, and tumor induction in beagle dogs.
AB  - The influence of age at injection of 226Ra or 239Pu on skeletal deposition and
      local distribution, the pattern of bone tumor formation, and postinjection
      survival was assessed in parallel short-term studies of mechanisms and lifetime
      toxicity. Beagles received a single intravenous injection of 226Ra or 239Pu at 3
      months (juveniles), 17-19 months (young adults) or 60 months (mature). Data from
      short-term studies of mechanisms and dosimetry and from one dosage level (41 kBq
      226Ra/kg or 11 kBq 239Pu/kg body mass) of each of the toxicity experiments were
      compared. Skeletal growth and turnover produced differential initial deposition
      and distribution patterns typical for each age group. At 1 week after injection,
      skeletal retention of 226Ra or 239Pu was 68 and 68%, respectively, in the
      juveniles, 32 and 46% in the young adults, and 31 and 43% in the mature dogs.
      Comparing individual bones in the juveniles, gradients in the concentration of
      239Pu were small since all bones were actively growing, but substantial
      gradients, corresponding to centers of ossification, were present within
      individual bones. In other age groups, local concentration gradients were less
      pronounced, but much larger differences were present among the various bones. In
      the toxicity study all animals injected with either 41 kBq 226Ra/kg or 11 kBq
      239Pu/kg have died. The cumulative average skeletal doses to the presumed time of
      start of tumor growth (1 year before death) were 25 and 4 Gy, respectively, for
      the juveniles, 22 and 5 Gy for the young adults, and 15 and 4 Gy for the mature
      dogs. The highest bone tumor incidence was seen in the young adult groups.
      Differences were observed in location of bone tumors between dogs in the same age
      group given radium or plutonium and among age groups injected with either
      radionuclide, some of which could be explained by differences in local dose
      distributions. Median postinjection survival assessed by the Kaplan-Meier
      nonparametric method ranged from 2513 and 2592 days for the juveniles to 2099 and
      1617 for the young adults to 2086 and 1421 in the mature groups. Cox regression
      analysis indicated no significant differences in postinjection survivals
      (uncorrected for the different preinjection periods) of groups injected with
      radium, but there was a statistically significant difference among the groups
      injected with plutonium. It was demonstrated that differences in the effects of
      239Pu in the three groups were due primarily to the age- and time-dependent local
      distribution of the radionuclide.

PMID- 2000448
TI  - The simultaneous determination of intracellular pH and cell energy status.
AB  - The relationship between the apparent equilibrium constant of creatine kinase and
      intracellular pH was evaluated in CHO and murine FSaII tumor cells. The apparent
      equilibrium constant, K' = [ATP][Cr]/[ADP][PCr], was determined from acid
      extracts at variable pH. Intracellular pH (pHi) was determined from the
      intracellular/extracellular distribution of the weak acid 5,5-dimethyl-2,4
      oxazolidinedione. Over the intracellular pH range of 7.2 to 6.1, K' increased by
      a factor of approximately 10. Intracellular pH was related to the apparent
      equilibrium constant by the equation pHi = -log K' + log K, where the value of
      the constant log (log[K'/H+]) was 8.09. Over the same pH range, the concentration
      of phosphocreatine decreased with pH. Essentially identical results were obtained
      in CHO and FSaII tumor cells. The similar apparent equilibrium constants in CHO
      and FSaII cells suggest that assessment of the creatine kinase metabolites will
      be useful not only for determination of cell energy status but also for the
      determination of intracellular pH. This information may be useful for the design
      of therapeutic strategies which are influenced by pH or energy status such as
      hyperthermia, and drugs which are weak acids or bases, including hypoxic cell
      radiosensitizers.

PMID- 2000449
TI  - Reduction of radiation-induced cell cycle blocks by caffeine does not necessarily
      lead to increased cell killing.
AB  - The effect of caffeine upon the radiosensitivities of three human tumor lines was
      examined and correlated with its action upon the radiation-induced S-phase and G2
      phase blocks. Caffeine was found to reduce at least partially the S-phase and G2
      phase blocks in all the cell lines examined but potentiated cytotoxicity in only
      one of the three tumor lines. That reductions have been demonstrated to occur in
      the absence of increased cell killing provides supporting evidence for the
      hypothesis that reductions may not be causal in those cases when potentiation of
      radiation-induced cytotoxicity is observed in the presence of caffeine.

PMID- 2000450
TI  - Depletion of glutathione after gamma irradiation modifies survival.
AB  - The relationship between the intracellular glutathione (GSH) concentration and
      the aerobic radiation response was studied in Chinese hamster ovary cells.
      Various degrees of GSH depletion were produced by exposure to buthionine
      sulfoximine (BSO) and/or diethyl maleate (DEM). Diethyl maleate did not act as a
      classical radiosensitizer under the experimental conditions employed, nor did
      exposure to DEM/BSO nonspecifically affect protein thiols as measured by thiol
      blotting. Dose-response curves were obtained using cells irradiated in the
      absence or presence of DEM/BSO, which decreased GSH levels by 90-95%. Exposure to
      DEM/BSO did not affect the formation of DNA single-strand breaks or DNA-protein
      crosslinks measured immediately after irradiation performed at ice temperatures.
      Analysis of survival curves indicated that the Dq was decreased by 18% when GSH
      depletion occurred prior to, during, and after irradiation. The DEM/BSO exposure
      did not affect D0. To study postirradiation conditions, cells were exposed to 10
      microM DEM prior to and during irradiation, which was performed at ice
      temperatures. Levels of GSH were depleted by 75% by this protocol. Immediately
      after irradiation, the cells were rapidly warmed by the addition of 37 degrees C
      growth medium containing either 10 or 90 microM DEM. Addition of 10 microM DEM
      after irradiation did not affect the degree of depletion, which remained constant
      at 75%. In contrast, GSH depletion was increased to 90% 10 min after addition of
      the 90 microM DEM. Addition of 90 microM DEM after irradiation produced a
      statistically significant difference in survival compared to addition of 10
      microM DEM. In a second depletion protocol, cells were exposed to 100 microM DEM
      at room temperature for 5 min, irradiated, incubated at 37 degrees C for 1 h,
      washed, and then incubated in 50 microM BSO for 24 h. This depletion protocol
      reduced survival by a factor of 2.6 compared to cells not exposed to the
      combination of DEM/BSO. Survival was not affected if the cells were exposed to
      the DEM or BSO alone. This was interpreted to indicate that survival was not
      affected by GSH depletion occurring after irradiation unless depletion was rapid
      and sustained. The rate of repair of sublethal and potentially lethal damage was
      measured and found to be independent of the DEM/BSO exposure. These experimental
      results in addition to previous ones (Freeman and Meredith, Int. J. Radiat.
      Oncol. Biol. Phys. 13, 1371-1375, 1987) were interpreted to indicate that under
      aerobic conditions GSH depletion may alter the expression of radiation damage by
      affecting metabolic fixation.

PMID- 2000451
TI  - The response of ataxia-telangiectasia lymphoblastoid cells to neutron
      irradiation.
AB  - The response of control and ataxia-telangiectasia (A-T) cells to increasing doses
      of high-linear-energy-transfer (LET) ionizing radiation (neutrons) was compared.
      Ataxia-telangiectasia cells were markedly more sensitive to neutron irradiation
      than were control cells. The D0 value for the two A-T cell lines was 0.4 Gy while
      the value for controls was approximately 1.4 Gy. Fast neutrons were considerably
      more effective than gamma rays in inducing cell death in both cell types, but the
      sensitivity factor remained approximately the same as with gamma rays. A minimal
      depression of DNA synthesis was observed in ataxia-telangiectasia cells after
      neutron irradiation, similar to that reported previously after gamma irradiation.
      The extent of inhibition was not significantly greater in control cells, contrary
      to that seen with gamma rays. In time-course experiments a significant difference
      in degree of inhibition of DNA synthesis was observed between the cell types. Low
      doses of fast neutrons induced a G2-phase delay in both cell types, but the
      degree and extent of this delay was greater in ataxia-telangiectasia cells as
      observed previously with low-LET radiation.

PMID- 2000452
TI  - Increased G2 delay in radiation-resistant cells obtained by transformation of
      primary rat embryo cells with the oncogenes H-ras and v-myc.
AB  - Cell cycle perturbation after irradiation was studied in five cell lines
      transfected with oncogenes. Two immortalized, radio-sensitive cell lines with D0s
      of 1.06 and 1.08 Gy were compared to three radioresistant cell lines with D0s of
      1.68-2.17 Gy. The sensitive cell lines were transfected with the v-myc or c-myc
      oncogenes, the resistant cell lines with the v-myc plus H-ras oncogenes.
      Exponentially growing populations were exposed to 5, 10, or 15 Gy of orthovoltage
      radiation. The percentage of cells in each phase of the cell cycle was determined
      at various times after irradiation using flow cytometry. All cell lines underwent
      a dose-dependent arrest in G2 phase after irradiation, but the resistant cell
      lines underwent a significantly longer arrest in G2 phase after irradiation than
      did the sensitive cell lines. In conjunction with other results from our
      laboratories, we suggest that this difference in G2 arrest may be the basis for
      the increased resistance of cells transfected with oncogenes to irradiation.

PMID- 2000453
TI  - Radioprotection of mice by a single subcutaneous injection of heat-killed
      Lactobacillus casei after irradiation.
AB  - Treatment of whole-body gamma-irradiated mice with a preparation of Lactobacillus
      casei (LC 9018) immediately after irradiation caused a sustained increase in
      serum colony-stimulating activity which was followed by an enhanced repopulation
      of granulocyte-macrophage colony-forming cells in the femoral marrow and spleen.
      Numbers of blood leukocytes, erythrocytes, and platelets were increased earlier
      in the treated mice than in the controls, and the survival rate was elevated
      significantly. The radioprotective effect was dependent on the dose of LC 9018 as
      well as on the dose of radiation. These results demonstrate the value of LC 9018
      for the treatment of myelosuppression after radiotherapy or radiation accidents.

PMID- 2000454
TI  - Relative cataractogenic effects of X rays, fission-spectrum neutrons, and 56Fe
      particles: a comparison with mitotic effects.
AB  - The eyes of Sprague-Dawley rats were irradiated with doses of 2.5-10 Gy 250-kVp X
      rays, 1.25-2.25 Gy fission-spectrum neutrons (approximately 0.85 MeV), or 0.1-2.0
      Gy 600-MeV/A 56Fe particles. Lens opacifications were evaluated for 51-61 weeks
      following X and neutron irradiations and for 87 weeks following X and 56Fe
      particle irradiations. Average stage of opacification was determined relative to
      time after irradiation, and the time required for 50% of the irradiated lenses to
      achieve various stages (T50) was determined as a function of radiation dose. Data
      from two experiments were combined in dose-effect curves as T50 experimental
      values taken as percentages of the respective T50 control values (T50-% control).
      Simple exponential curves best describe dose responsiveness for both high-LET
      radiations. For X rays, a shallow dose-effect relationship (shoulder) up to 4.5
      Gy was followed at higher doses by a steeper exponential dose-effect
      relationship. As a consequence, RBE values for the high-LET radiations are dose
      dependent. Dose-effect curves for cataracts were compared to those for mitotic
      abnormalities observed when quiescent lens epithelial cells were stimulated
      mechanically to proliferate at various intervals after irradiation. Neutrons were
      about 1.6-1.8 times more effective than 56Fe particles for inducing both
      cataracts and mitotic abnormalities. For stage 1 and 2 cataracts, the X-ray Dq
      was 10-fold greater and the D0 was similar to those for mitotic abnormalities
      initially expressed after irradiation.

PMID- 2000455
TI  - Effect of caffeine on the expression of a major X-ray induced protein in human
      tumor cells.
AB  - We have examined the effect of caffeine on the concomitant processes of the
      repair of potentially lethal damage (PLD) and the synthesis of X-ray-induced
      proteins in the human malignant melanoma cell line, Ul-Mel. Caffeine administered
      at a dose of 5mM after X radiation not only inhibited PLD repair but also
      markedly reduced the level of XIP269, a major X-ray-induced protein whose
      expression has been shown to correlate with the capacity to repair PLD. The
      expression of the vast majority of other cellular proteins, including seven other
      X-ray-induced proteins, remained unchanged following caffeine treatment. A
      possible role for XIP269 in cell cycle delay following DNA damage by X
      irradiation is discussed.

PMID- 2000456
TI  - Radiation-induced skin carcinomas of the head and neck.
AB  - Radiation exposures to the scalp during childhood for tinea capitis were
      associated with a fourfold increase in skin cancer, primarily basal cell
      carcinomas, and a threefold increase in benign skin tumors. Malignant melanoma,
      however, was not significantly elevated. Overall, 80 neoplasms were identified
      from an extensive search of the pathology logs of all major hospitals in Israel
      and computer linkage with the national cancer registry. Radiation dose to the
      scalp was computed for over 10,000 persons irradiated for ringworm (mean 7 Gy),
      and incidence rates were contrasted with those observed in 16,000 matched
      comparison subjects. The relative risk of radiogenic skin cancer did not differ
      significantly between men or women or by time since exposure; however, risk was
      greatest following exposures in early childhood. After adjusting for sex, ethnic
      origin, and attained age, the estimated excess relative risk was 0.7 per Gy and
      the average excess risk over the current follow-up was 0.31/10(4) PY-Gy. The risk
      per Gy of radiation-induced skin cancer was intermediate between the high risk
      found among whites and no risk found among blacks in a similar study conducted in
      New York City (Shore et al., Radiat. Res. 100, 192-204, 1984). This finding
      suggests the role that subsequent exposure to uv radiation likely plays in the
      expression of a potential radiation-induced skin malignancy.

PMID- 2000457
TI  - Is interindividual variation of cellular radiosensitivity real or artifactual?
AB  - A recently developed dose-survival assay using human G0 T lymphocytes from
      peripheral blood was employed to assess possible interindividual variation of
      cellular radiosensitivity by comparing variability between a single test for
      different individuals and repeated tests for a single donor. The surviving
      fraction at each X-ray dose level fluctuated similarly between the two groups,
      and the X-ray dose required to kill 90% of the cells (D10) was 3.59 +/- 0.18 Gy
      (mean +/- SD) for 31 different individuals and 3.66 +/- 0.21 Gy for 28 repeated
      tests of one individual. Analysis of variance to compare the two sets of data
      showed that variation in the D10 value was not significantly greater in the
      former group. Analysis of D50 and D90 showed similar results. These results
      support the hypothesis that interindividual variation in cellular
      radiosensitivity is quite small, if it exists at all, as far as can be determined
      by the loss of colony-forming ability of irradiated G0 lymphocytes.

PMID- 2000458
TI  - Oncogenic transformation following sequential irradiations with monoenergetic
      neutrons and X rays.
AB  - Mouse C3H 10T1/2 cells were exposed sequentially to low doses (0.1 and 0.3 Gy) of
      monoenergetic neutrons (0.35, 0.45, 5.9, and 13.7 MeV) and 250-kVp X rays (1 and
      3 Gy). The incidences of oncogenic transformation in the cells exposed to
      neutrons followed by X rays indicated that the effects of the individual
      radiations were simply additive. This supports the contention that risks
      associated with the two different radiation modalities may be considered to be
      additive.

PMID- 2000459
TI  - Irradiation of cells attached or suspended by rubber policeman or by trypsin
      influences the extent of DNA strand breaks induced by ionizing radiation.
AB  - Chilled B16CL4 mouse melanoma cells in phosphate-buffered saline were exposed to
      ionizing radiation before or after harvesting by gently scraping with a rubber
      policeman. Cells irradiated when attached had fewer DNA strand breaks than cells
      that were irradiated in suspension. Dose-response studies indicate that the rate
      of induction of DNA strand breaks by ionizing radiation is 1.5-fold greater in
      suspended cells. Irradiation after release of the cells by trypsinization also
      results in more breaks than irradiation when attached, but this method of harvest
      is not as damaging as release by rubber policeman. Strand breaks in unirradiated
      cells are unaffected by the method of cell harvest. These studies suggest that,
      in radiation studies, care should be exercised to avoid the introduction of
      artifacts resulting from the methods used to harvest and irradiate cells.

PMID- 2000460
TI  - The distance over which a misonidazole molecule can trap mobile electrons in DNA.

PMID- 2000461
TI  - Comments on the estimated distance over which electrons can migrate in solid DNA
      before being trapped by misonidazole.

PMID- 2000462
TI  - The mental health professional and the legal system. Committee on Psychiatry and
      Law. Group for the Advancement of Psychiatry.

PMID- 2000463
TI  - Rehabilitation nursing approaches to cerebrovascular accident: a comparison of
      two approaches.
AB  - The purpose of this study was to compare patients receiving neurodevelopmental
      therapy (NDT) to patients receiving a traditional approach. The study took place
      on two separate medical rehabilitation units, each using just one approach.
      Patients were assigned to each unit based upon bed availability. The charts of 43
      cerebral vascular accident (CVA) patients who received the traditional approach
      and of 37 CVA patients who received NDT were audited for demographic, functional,
      and disposition data. No significant differences at admission were found between
      the two groups, except that the NDT group had higher scores in dressing (p = .04)
      and toileting (p = .02). At discharge, the NDT group had higher functioning
      scores on toileting only (p = .03). Length of stay was almost identical between
      the two groups. Eighty-six percent of the NDT sample were discharged home
      compared to 78% of the traditional sample, but this was not statistically
      significant. Thus, the NDT approach does not appear to be superior to the
      traditional approach. These results imply that there needs to be more careful
      study of rehabilitation approaches before committing to one specific approach in
      the nursing care of CVA patients.

PMID- 2000464
TI  - The development of the RISK tool for fall prevention.
AB  - The authors tailored a 26-item risk assessment tool (RAT) for falls based on a
      literature review and an analysis of causative factors of falls that had occurred
      over a 3-month period at the Olin E. Teague VA Medical Center, an 1,100-bed acute
      medical-surgical, psychiatric, and extended care facility in Temple, TX. The RAT
      was completed by nursing staff on 10 patient units (four medical, four surgical,
      and two nursing home units) for all admissions during the period. A 25% sample of
      the completed RATs was randomly selected (n = 208). Pearson's correlation
      coefficient was used to identify factors that would most likely predict falls
      from the RATs of the randomly selected group and of the patients who fell (n =
      78). Only 4 of the 26 items were statistically related to falls. Based on
      findings from this study, the RAT was shortened to the four items and called the
      RISK (Reassessment Is Safe "Kare") tool.

PMID- 2000465
TI  - Integrating rehabilitation content in nursing curricula.
AB  - The faculty of the department of nursing of Simmons College in Boston revised its
      curriculum using Betty Neuman's Neuman Systems Model (1982) as the conceptual
      framework. Content essential to the nursing curriculum was identified, logically
      grouped, and then leveled for correct sequencing. During senior year (level III
      of the curriculum), when tertiary preventions were being integrated, students
      received theoretical content and specific learning experiences with clients in a
      rehabilitation setting. This article describes the content included, teaching
      methodologies used, and the selection of the clinical placement. Data from
      formative and summative evaluations, as well as modifications for the third year,
      also are included.

PMID- 2000466
TI  - Nursing care of clients with impaired communication.
AB  - Communication is a universal, dynamic process by which human beings exchange
      ideas and express needs. Strokes are a major cause of impaired communication, and
      rehabilitation nurses work closely with these clients and their families to help
      them cope with deficits, especially aphasia. This article defines speech and
      language and their physiological and psychosocial aspects, as well as three types
      of aphasia. Finally, nursing interventions for clients with impaired
      communication are suggested.

PMID- 2000467
TI  - Preparing case reports as a nurse legal consultant.
AB  - Nurses acting as legal consultants in malpractice, workers' compensation, or
      personal injury litigation may be asked to provide a report that assesses a
      client's past, present, and future healthcare needs. This article describes the
      composition of such a report, using the nursing process and nursing models. The
      format illustrates the comprehensive nature of a nurse's contribution to the
      resolution of legal actions.

PMID- 2000468
TI  - Effective communication with autistic children.
AB  - Autism is a lifelong developmental disability manifested before the age of 2 1/2
      years (Wing, 1974). Autistic children exhibit language retardation with impaired
      comprehension. To maximize effective communication with these children, nurses
      must know how they communicate and be aware of natural, but detrimental,
      responses to their behaviors.

PMID- 2000469
TI  - Easing the impact of the family caregiver's role.
AB  - This article describes problems facing family caregivers of elderly, ill, or
      disabled people. The physical and emotional impact of caregiving is explored, and
      the concept of role fatigue is discussed to assist nurses in understanding
      caregivers' problems and needs. Motivational factors for becoming a caregiver and
      community sources of support are addressed. Rehabilitation nurses are challenged
      both to accept the responsibility of identifying caregiver role problems, and to
      help caregivers obtain assistance that will enable them to continue family
      members' care in a home environment.

PMID- 2000470
TI  - Effects of low-intensity aerobic exercise on one subject with chronic-relapsing
      Guillain-Barre syndrome.

PMID- 2000471
TI  - Ethics of electroconvulsive therapy consent.

PMID- 2000472
TI  - Respiratory syncytial virus infections at Rhode Island Hospital: use of
      ribavirin.

PMID- 2000473
TI  - Infections, preterm delivery, and perinatal death in midgestation.
AB  - Amniotic fluid infection results in considerable pregnancy wastage in the second
      and early third trimesters. In our study of 1119 perinatal autopsies amniotic sac
      infection was associated with death in 133 fetuses and neonates in midgestation.
      These cases accounted for almost 12% of all perinatal autopsies and for 20% of
      all perinatal autopsies in midgestation at Women and Infants Hospital during the
      past decade. Gram-positive organisms, especially coagulase negative
      staphylococcus, group B streptococcus and Streptococcus viridans, were the most
      common pathogens isolated.

PMID- 2000474
TI  - Orphan viruses in search of disease.

PMID- 2000475
TI  - Acute bacterial meningitis in Rhode Island: a survey of the years 1976 to 1985.
AB  - There were 667 recorded cases of bacterial meningitis in the hospitals of Rhode
      Island during the ten year interval of 1976 to 1985 yielding an average annual
      incidence rate of 6.9 cases per 100,000 population, and a case fatality rate of
      10.3%. These rates are similar to those generated in other retrospective surveys
      in the United States. This survey corroborates the well-established observation
      that bacterial meningitis is largely a disease of early childhood. But these data
      also suggest that meningitis in the very elderly is more common than had
      previously been assumed. Many of the elderly cases in this series, particularly
      those caused by the coliform organisms, followed shortly after body trauma or
      appeared in individuals burdened by disseminated cancer or diabetes mellitus.

PMID- 2000476
TI  - Measles 1990.

PMID- 2000477
TI  - Three components of formal medical education.

PMID- 2000478
TI  - Life in the blood. Growth factors replenish the body's most important cells.

PMID- 2000479
TI  - Reach out. Touch is added to virtual reality simulations.

PMID- 2000480
TI  - The A team. Vitamin A and its cousins are potent regulators of cells.

PMID- 2000481
TI  - Postal mortem. Drug test results may point to racial discrimination.

PMID- 2000482
TI  - Nuclear numbers. Living near power reactors may not add cancer risk.

PMID- 2000483
TI  - The physiology of perception.

PMID- 2000484
TI  - X-ray microscopes.

PMID- 2000485
TI  - Views of the genome project.

PMID- 2000486
TI  - Aging studies.

PMID- 2000487
TI  - Comparison of two forms of long-term potentiation in single hippocampus neurons.
      Correction.

PMID- 2000488
TI  - Flap erupts over dioxin meeting.

PMID- 2000489
TI  - Systematics goes molecular.

PMID- 2000490
TI  - DNA: a model compound for solution studies of macromolecules.
AB  - Well-defined, monodisperse, homologous series of oligonucleotides and DNA
      restriction fragments may now be produced and used as models of rigid and
      semirigid rodlike molecules in solution. Information from optical experiments on
      these model systems aids in the formulation and testing of theories of
      macromolecular dynamics in both dilute and concentrated solution.

PMID- 2000491
TI  - Charge separation in a reaction center incorporating bacteriochlorophyll for
      photoactive bacteriopheophytin.
AB  - Site-directed mutagenic replacement of M subunit Leu214 by His in the
      photosynthetic reaction center (RC) from Rhodobacter sphaeroides results in
      incorporation of a bacteriochlorophyll molecule (BChl) in place of the native
      bacteriopheophytin (BPh) electron acceptor. Evidence supporting this conclusion
      includes the ground-state absorption spectrum of the (M)L214H mutant, pigment and
      metal analyses, and time-resolved optical experiments. The genetically modified
      RC supports transmembrane charge separation from the photoexcited BChl dimer to
      the primary quinone through the new BChl molecule, but with a reduced quantum
      yield of 60 percent (compared to 100 percent in wild-type RCs). These results
      have important implications for the mechanism of charge separation in the RC, and
      rationalize the choice of (bacterio)pheophytins as electron acceptors in a
      variety of photosynthetic systems.

PMID- 2000492
TI  - Chemical sensors based on controlled-release polymer systems.
AB  - A novel chemical sensor has been developed in which the polymer ethylene-vinyl
      acetate is used as a controlled-release system to deliver reagents to the sensing
      region of an optical fiber for a homogeneous competitive immunoassay based on
      fluorescence energy transfer. A competition reaction is used to enable continuous
      measurements of the solution antigen concentration. More generally, the technique
      allows irreversible indicating chemistries to be used in the construction of
      chemical sensors that can measure continuously for long periods. Although the
      sensor configuration has not been optimized in all respects, data are presented
      for a model system in which a fluorescein-labeled antibody and Texas Red-labeled
      immunoglobulin G (IgG) are used.

PMID- 2000493
TI  - Distinctive cranial and cervical innervation of wing muscles: new evidence for
      bat monophyly.
AB  - The traditional view that Old World fruit bats (Megachiroptera) and insect bats
      (Microchiroptera) are closely related has been challenged by claims that
      Megachiroptera are the sister group to flying lemurs (Dermoptera) or Primates. We
      found that the specialized muscles of the rostral part of the wing in
      Microchiroptera and Megachiroptera receive double innervation by both the facial
      nerve and cervical spinal nerves, suggesting that bats are monophyletic.
      Innervation by the facial nerve also occurs in Dermoptera and suggests that bats
      and Dermoptera share a common ancestor that had wings.

PMID- 2000494
TI  - Mutations affecting internal TEA blockade identify the probable pore-forming
      region of a K+ channel.
AB  - The active site of voltage-activated potassium channels is a transmembrane
      aqueous pore that permits ions to permeate the cell membrane in a rapid yet
      highly selective manner. A useful probe for the pore of potassium-selective
      channels is the organic ion tetraethylammonium (TEA), which binds with millimolar
      affinity to the intracellular opening of the pore and blocks potassium current.
      In the potassium channel encoded by the Drosophila Shaker gene, an amino acid
      residue that specifically affects the affinity for intracellular TEA has now been
      identified by site-directed mutagenesis. This residue is in the middle of a
      conserved stretch of 18 amino acids that separates two locations that are both
      near the external opening of the pore. These findings suggest that this conserved
      region is intimately involved in the formation of the ion conduction pore of
      voltage-activated potassium channels. Further, a stretch of only eight amino acid
      residues must traverse 80 percent of the transmembrane electric potential
      difference.

PMID- 2000495
TI  - Exchange of conduction pathways between two related K+ channels.
AB  - The structure of the ion conduction pathway or pore of voltage-gated ion channels
      is unknown, although the linker between the membrane spanning segments S5 and S6
      has been suggested to form part of the pore in potassium channels. To test
      whether this region controls potassium channel conduction, a 21-amino acid
      segment of the S5-S6 linker was transplanted from the voltage-activated potassium
      channel NGK2 to another potassium channel DRK1, which has very different pore
      properties. In the resulting chimeric channel, the single channel conductance and
      blockade by external and internal tetraethylammonium (TEA) ion were
      characteristic of the donor NGK2 channel. Thus, this 21-amino acid segment
      controls the essential biophysical properties of the pore and may form the
      conduction pathway of these potassium channels.

PMID- 2000497
TI  - Form, motion, and binocular rivalry.

PMID- 2000496
TI  - Reshaping the cortical motor map by unmasking latent intracortical connections.
AB  - The primary motor cortex (MI) contains a map organized so that contralateral limb
      or facial movements are elicited by electrical stimulation within separate medial
      to lateral MI regions. Within hours of a peripheral nerve transection in adult
      rats, movements represented in neighboring MI areas are evoked from the cortical
      territory of the affected body part. One potential mechanism for reorganization
      is that adjacent cortical regions expand when preexisting lateral excitatory
      connections are unmasked by decreased intracortical inhibition. During
      pharmacological blockade of cortical inhibition in one part of the MI
      representation, movements of neighboring representations were evoked by
      stimulation in adjacent MI areas. These results suggest that intracortical
      connections form a substrate for reorganization of cortical maps and that
      inhibitory circuits are critically placed to maintain or readjust the form of
      cortical motor representations.

PMID- 2000498
TI  - Recurring osteoblastoma initially presenting as a typical osteoid osteoma. Report
      of two cases.
AB  - Two patients each underwent inadequate excision of an osteoid osteoma and some
      months later developed a large tumor in the same location showing the
      radiographical and histological features of osteoblastoma. This rare occurrence
      again suggests that osteoid osteoma and osteoblastoma are closely connected
      benign neoplasms. Indeed some authors in the past have suggested classification
      as a single tumor showing different clinical and radiographical patterns.

PMID- 2000499
TI  - Contrast and nuclear arthrography in loosening of the uncemented hip prosthesis.
AB  - The recent popularity of ingrowth or uncemented hip arthroplasties has presented
      problems in the radiographic diagnosis of loosening because there is no longer a
      cement interface in which lucencies may be seen. We evaluated a combination of
      positive contrast and nuclear arthrography to see whether these studies could
      accurately detect loosening of uncemented femoral components of hip prostheses.
      We performed routine contrast and nuclear arthrography in 21 patients with
      ingrowth total hip arthroplasties or bipolar endoprostheses. The results were
      surgically confirmed in 12 patients. The contrast arthrogram was true positive in
      5 and false negative in 5. There were no false positives and 2 true negatives.
      The nuclear arthrogram was true positive in 7 patients, false negative in 3, and
      true negative in 2. Taken together, there was only 1 patient in whom both
      contrast and nuclear arthrography were false negative, and there were no false
      positives. Thus, when either contrast or nuclear arthrography is positive, the
      sensitivity of the combined procedures is 90%; when both studies are negative,
      the specificity is 100%. The combination of contrast and nuclear arthrography is
      an accurate method of determining loosening of the femoral component of an
      uncemented hip arthroplasty or bipolar endoprosthesis in the patient with
      postoperative hip pain.

PMID- 2000500
TI  - Calcific tendinitis of the vastus lateralis muscle. A report of three cases.
AB  - Three cases of calcific tendinitis occurring at an unusual site (vastus lateralis
      tendon) are described. Findings on conventional radiography and computed
      tomography together with the clinical history are characteristic for this
      disorder and reflect its natural evolution. The actual role of magnetic resonance
      imaging seems limited to excluding neoplasm and to demonstrating inflammatory
      changes better in the early stages of disease.

PMID- 2000501
TI  - Accuracy of vertebral mineral determination by dual-energy quantitative computed
      tomography.
AB  - Quantitative computed tomography is an established method for the non-invasive
      assessment of bone mineral content. Scanning with two different X-ray energies
      allows material-selective image reconstruction and separation on the basis of
      differing atomic numbers. As proven by chemophysical analysis of 45 bone samples,
      dual-energy quantitative computed tomography with basis material decomposition
      allows highly accurate measurement of bone mineral density with an error of 1.4%,
      independent of fat and soft tissue content.

PMID- 2000502
TI  - Magnetic resonance imaging reflects cartilage proteoglycan degradation in the
      rabbit knee.
AB  - Cartilage degeneration in osteoarthritis is initiated by a loss of proteoglycan.
      Intra-articular injection of papain causes a reversible loss of proteoglycan in
      rabbit knees. Rabbits were scanned with magnetic resonance imaging (MRI), using a
      1.5T Signa superconducting magnet with 3 inch surface coil. Spin echo sequences
      were performed in the coronal and sagittal planes at 0, 24, 48, and 72 h after
      intra-articular injection of papain to obtain T1, proton density, and T2-weighted
      images. Cartilage proteoglycan content was measured biochemically and
      histochemically. Reduced articular cartilage thickness in the MR images of papain
      treated knees corresponded to changes in cartilage proteoglycan content.

PMID- 2000503
TI  - Radiographic features of craniometadiaphyseal dysplasia, wormian bone type.
AB  - We describe the radiographic findings in two siblings with a previously
      unrecognized craniotubular bone dysplasia. We call this condition
      craniometadiaphyseal dysplasia, wormian bone type. Because the parents of the
      siblings are consanguineous, this is probably a genetically determined condition
      with an autosomal recessive type of transmission. The findings in the siblings
      are compared with those of a woman with the same condition, previously reported
      as an example of craniometaphyseal dysplasia. The combination of findings in
      these patients seems diagnostic: characteristic skull changes including multiple
      wormian bones; wide long tubular bones without normal metaphyseal flaring; wide
      short tubular bones without normal diaphyseal constriction and sometimes actual
      diaphyseal expansion; and wide ribs and clavicles.

PMID- 2000504
TI  - Case report 632. Parosteal osteochondromatous hamartoma associated with Trevor's
      disease (dysplasia epiphysealis hemimelica).
AB  - The current case represents a patient with classic plain film findings of
      Trevor's disease (DEH) seen in the foot and ankle, who presented with a large,
      eccentric metaphyseal lesion in the ipsilateral distal femur. The radiographic
      and pathologic characteristics of this large metaphyseal lesion were considered
      atypical for a simple osteochondroma; therefore, we propose the term "parosteal
      osteochondromatous hamartoma" as a descriptive term that best fits its unique
      characteristics.

PMID- 2000505
TI  - Diagnostic potential of double contrast arthrography of the knee with the digital
      technique.
AB  - Experience with digital radiography applied to double contrast arthrography of
      the knee performed with a photostimulable phosphor plate is reported. The image
      processing technique used to improve the digital image is described, and some
      theoretical considerations are discussed. A preliminary comparison is also made
      between arthrographic images obtained with conventional screen-film systems and
      the digital system, especially in respect of the image quality and visualization
      of the soft tissue structures least well demonstrated with conventional
      arthrography.

PMID- 2000506
TI  - Case report 647: Benign osteoblastoma causing spinal cord compression and spastic
      paresis.
AB  - Osteoblastoma is an infrequent but important cause of pain in the back and
      neurological findings in children and young adults. Its diagnosis may be
      difficult and often delayed (in one series, 23% of patients had not been
      diagnosed after 2 years of symptoms). MRI may be useful to noninvasively image
      the lesion, its soft tissue and bony extent and its relationship, if any, to the
      spinal cord.

PMID- 2000508
TI  - Case report 649: Arteriovenous malformation (arteriovenous hemangioma) of the
      distal thigh with bone involvement.
AB  - The case discussed is that of a 31-year-old woman with long-standing hypertrophy
      and vascular symptoms of the right lower extremity. The etiology of these
      abnormalities remained undiagnosed, although the patient was treated
      symptomatically. Following presentation, both MR images and contrast-enhanced CT
      scans were adequate for diagnosis of the underlying arteriovenous malformation.
      This was confirmed by arteriography, and the patient received palliative
      treatment by sequential intra-arterial embolization.

PMID- 2000507
TI  - Case report 648: Parosteal osteosarcoma arising from the right temporal bone.

PMID- 2000509
TI  - Case report 650: Grade II chondrosarcoma of the proximal end of the right femur.
AB  - A case is presented in which the conventional radiograph was suggestive of
      avascular necrosis. This impression remained unchanged inspite of an MRI
      examination that was more suggestive or replacement of marrow. The diagnosis of
      ischemic necrosis was strongly supported by the patient having previously
      established avascular necrosis in the opposite hip. The gross pathologic specimen
      showed only necrotic tumor, which mimicked avascular necrosis on the plain film.
      The importance of placing proper confidence in the MRI findings is thus
      emphasized. A classification and brief description of the various types of
      chondrosarcoma are included in the Discussion.

PMID- 2000510
TI  - Case report 651: Thrombosed, leaking popliteal aneurysm.
AB  - A thrombosed, leaking aneurysm of the popliteal artery, mimicking a soft tissue
      sarcoma both clinically and by MRI examination, is described. It may be difficult
      to separate a leaking, thrombosed aneurysm from an inflammatory response
      secondary to a sarcoma with intralesional hemorrhage. An aneurysm should,
      however, be considered in the differential diagnosis if the mass is present in a
      well-recognized location for aneurysm and is associated with vascular engulfment
      and signs of subacute or chronic hemorrhage.

PMID- 2000511
TI  - Case report 652: Primary intraosseous low grade myxoid sarcoma of the scapula
      (myxoid liposarcoma).
AB  - A case of primary liposarcoma of bone involving the glenoid region of the right
      scapula in a 57-year-old man is presented. The diagnosis was confirmed by open
      biopsy. The differential diagnoses have been considered. To the best of our
      knowledge, this may be the first reported case of primary liposarcoma of bone in
      the scapula.

PMID- 2000512
TI  - The flaming P pot.

PMID- 2000513
TI  - The road to education.

PMID- 2000514
TI  - Screening for sexually transmitted diseases by primary care physicians.
AB  - The acquired immunodeficiency syndrome epidemic has drawn attention to screening
      for sexually transmitted diseases by primary care physicians. A telephone survey
      of primary care physicians in an area with a high incidence of STDs (Washington,
      DC) to ascertain the determinants and the extent of screening and counseling for
      STDs was completed in 1987. Ninety-nine physicians (33 internists, 38
      obstetrician/gynecologists, and 28 family/general practitioners), representing
      61% of those eligible, completed the interview. One third (39.4%) were screening
      for gonorrhea, more than one half (57.5%) for syphilis, and almost all (94%) had
      tested at least one individual for human immunodeficiency virus infection.
      Analysis suggested that concomitant screening for hepatitis B was significantly
      and positively associated with screening for gonorrhea and syphilis. Less than
      half (45.9%) of the physicians asked new patients about their sexual practices.
      Physicians should take histories of sexual practices and do more preventive
      counseling.

PMID- 2000515
TI  - Community-acquired pulmonary infections in a public municipal hospital in the
      1980s.
AB  - The relative and absolute incidences of community-acquired bacterial and
      tuberculous pulmonary infections, in patients admitted to a public municipal
      hospital, and the clinical and radiographic characteristics of these infections
      were retrospectively determined for the first time in 20 years. The data were
      compared to those previously reported in the literature. Such data were also
      specifically determined for alcoholics and compared to those found in
      nonalcoholics. The absolute numbers of infections due to pneumococci and
      anaerobes, and to tuberculosis, were not dissimilar to those reported in the
      literature, even though relatively few hemophilus infections were documented. The
      lack of Klebsiella sp infections was remarkable but not unexpected. Alcoholic
      patients had significantly higher rates of tuberculosis, cavitary disease, lung
      disease presumably due to anaerobes, and blood-culture-positive pneumonia. The
      relative concordance of our results for bacterial and tuberculous infections with
      those predicted from the published literature was striking. The high frequency of
      tuberculosis in our patients was particularly striking at a time when the
      incidence of tuberculosis nationwide, in patients without acquired
      immunodeficiency syndrome, has declined significantly.

PMID- 2000516
TI  - False-positive results in serologic tests for Rocky Mountain spotted fever during
      pregnancy.
AB  - The data from this study demonstrate that false-positive results from tests for
      Rocky Mountain spotted fever increase with the duration of pregnancy. The sera of
      4.0% (2/50) of women in their first trimester of pregnancy, 10.9% (5/46) in their
      second trimester, and 12.1% (12/99) in their third trimester yielded false
      positive results from latex agglutination assays for Rickettsia rickettsii
      infections. The cause of these false-positive results was not determined by this
      study. These false-positive titers were not associated with clinical findings or
      other laboratory abnormalities. Even though these sera did not contain antibodies
      to R rickettsii detectable by indirect fluorescent antibody testing, such false
      positive results from serologic tests for Rocky Mountain spotted fever can
      obscure the patient's correct diagnosis. This may lead to the unnecessary use of
      potentially toxic antibodies and prevent initiation of appropriate therapy.

PMID- 2000517
TI  - Transdermal clonidine versus chlordiazepoxide in alcohol withdrawal: a
      randomized, controlled clinical trial.
AB  - In a prospective, double-blind comparison, we assessed the efficacy of
      transdermal clonidine with that of chlordiazepoxide in the treatment of
      moderately severe acute alcohol withdrawal syndrome. While having significant
      withdrawal symptoms, 50 hospitalized men were randomly assigned to receive either
      transdermal clonidine or chlordiazepoxide over a 4-day study period. Outcome was
      evaluated daily, medically and psychiatrically, using both objective and
      subjective measurements for dependent variables. No patient in either study group
      had seizures or progression to delirium tremens. The group receiving transdermal
      clonidine had a more significant response globally for the signs and symptoms of
      alcohol withdrawal, as measured by the Alcohol Withdrawal Assessment Scale. Also,
      clonidine more effectively lowered elevated systolic and diastolic blood pressure
      and heart rate. The core target symptom, anxiety, decreased significantly more in
      the patients receiving transdermal clonidine when measured by the Hamilton
      Anxiety Rating Scale and its subscale for somatic anxiety. Cognitive function
      responded equally in both study populations. Clonidine-treated patients reported
      less diarrhea, dizziness, headache and fatigue, and the chlordiazepoxide-treated
      patients reported less nausea and vomiting. We conclude that transdermal
      clonidine is effective treatment for the acute alcohol withdrawal syndrome.

PMID- 2000518
TI  - Patients with mental disorders who work.
AB  - Mental illness can devastate persons intellectually and emotionally; with
      maintenance therapy, however, certain patients with chronic mental illnesses are
      capable of holding a variety of jobs. From the total population of psychiatric
      patients in our VA outpatient clinic, the 87 who were gainfully employed were
      identified to determine common factors among them. Affective disorders were the
      predominant diagnoses among patients who worked, while schizophrenia was more
      common among those who did not. Alcoholism was diagnosed in approximately 25% of
      working and nonworking groups.

PMID- 2000519
TI  - Long-term medical consequences of incest, rape, and molestation.
AB  - One hundred thirty-one patients who gave a history of childhood sexual abuse were
      seen in a general medical practice decades after the event and were compared with
      a control group. The subject patients were found to be distinct for chronic
      depression, morbid obesity, marital instability, high utilization of medical
      care, and certain psychosomatic symptoms, particularly chronic gastrointestinal
      distress and recurrent headaches. It is clear that these remote events can
      underlie difficult chronic medical problems. Questions about childhood sexual
      abuse must become part of the practitioner's review of systems in these difficult
      cases, if not routinely.

PMID- 2000520
TI  - Duodenal stricture: a complication of chronic fibrocalcific pancreatitis.
AB  - Over the past 10 years, one of us (M.C.A.) has treated 92 patients who required
      operation for symptoms associated with alcohol-induced chronic fibrocalcific
      pancreatitis. Four of these patients had duodenal obstruction. All four had had
      lateral pancreaticojejunostomy to relieve pancreatic ductal obstruction and
      associated chronic abdominal pain; three of the four also required biliary
      diversion for stenosis of the intrapancreatic portion of the common bile duct.
      Each duodenal stricture required reoperation and gastrojejunostomy to bypass the
      site of obstruction. A review of the English language literature revealed that
      duodenal obstruction in patients with chronic fibrocalcific pancreatitis is
      uncommon, only 58 previous cases having been reported. All of those patients had
      pancreatic ductal obstruction, and more than half had concomitant distal biliary
      stenosis. Two thirds of the duodenal obstructions were treated by
      gastroenterostomy, and one third were resected. Duodenal obstruction in patients
      with chronic pancreatitis and biliary stricture appears to reflect an advanced
      form of the disease. Combined lateral pancreaticojejunostomy and biliary
      diversion has emerged as the preferred surgical procedure for this problem.
      Careful preoperative assessment for evidence of duodenal stenosis also is needed
      in this group of patients, and gastroenterostomy is indicated in appropriate
      cases.

PMID- 2000521
TI  - Pediatric injury surveillance: use of a hospital discharge data base.
AB  - Mortality data traditionally have been used to describe the epidemiology of
      childhood injury. Fatal outcomes, however, represent less than 1% of injury
      events and thus provide a limited characterization of the problem. Future
      epidemiologic study resulting in injury prevention depends upon the development
      of morbidity-based injury surveillance systems. "E-coded" hospital discharge data
      bases (used to indicate external cause of injury) are a valuable source of
      information for monitoring and controlling serious, nonfatal injuries. An E-coded
      injury discharge data base was developed and evaluated at The Children's Hospital
      of Alabama in Birmingham. In addition to patient demographics, length of stay,
      total charge, and method of payment, E-code and "N-code" (to indicate the
      anatomic site of injury) data were collected. During the 2-year study period,
      1077 discharges from the hospital were documented in children with serious
      injuries under 15 years of age for an adjusted discharge rate of 78.0 per 10,000
      child-years. Injuries accounted for $5.3 million in total charges and 4899 total
      days of stay. Falls, unintentional poisonings, burns, and bicycle, motor vehicle
      passenger, and motor vehicle-pedestrian injuries were the six most common causes
      of injury. Closed-head trauma accounted for 55.4% of motor vehicle-passenger
      injuries, 67.6% of bicycle injuries, and 51.8% of falls. Hot water scalds caused
      36.4% of burns, and clonidine ingestion accounted for 22.1% of unintentional
      poisonings.

PMID- 2000522
TI  - Fatal incidents involving pickup trucks in Alabama.
AB  - Death or injury resulting from crashes involving light trucks (ie, pickup trucks)
      is a significant problem. Data show that fatal crashes and occupant fatalities
      involving light trucks have steadily increased since 1983. This project describes
      vehicle crashes involving passengers riding in the beds of pickup trucks. Actual
      crashes were identified through the Fatal Accident Reporting System (FARS) of the
      National Highway Traffic Safety Administration. The 40 incidents studied involved
      204 pickup truck passengers. Of these, 45 were killed, 107 sustained visible
      injuries or were carried from the scene, 6 had bruises and abrasions, and 2 had
      no visible injury but were briefly unconscious or had a documented complaint of
      pain. The risk of death among pickup truck passengers who were fully ejected from
      the vehicle was nearly six times that of passengers not fully ejected.
      Correspondingly, the risk of ejection from the truck was 26.7 times greater among
      occupants riding in the bed than occupants riding in the cab.

PMID- 2000523
TI  - Howard Atwood Kelly (1858-1943): his life and his enduring legacy.

PMID- 2000524
TI  - Complete atrioventricular block due to sublingual isosorbide dinitrate.

PMID- 2000525
TI  - Scalp pilomatrix carcinoma as an extra-axial mass.
AB  - We report the CT, MRI, and angiographic findings in a case of pilomatrix
      carcinoma that had invaded the temporal bone and presented itself as an extra
      axial mass. Even though bone destruction was better shown with CT, the tumor mass
      with its meningeal and tentorial extension was seen more clearly with MRI. The
      arteriogram demonstrated a unique vascular supply from the external carotid
      artery.

PMID- 2000526
TI  - Cerebral falciparum malaria mimicking thrombotic thrombocytopenic purpura.
AB  - We have described a patient with cerebral falciparum malaria who had rapidly
      progressive CNS deterioration, renal failure, hemolytic anemia associated with
      striking and varied erythrocyte morphologic changes, and thrombocytopenia. The
      initial diagnosis was thrombotic thrombocytopenic purpura (TTP) of unknown
      origin. Reexamination of the peripheral smear of this comatose patient led to
      correct diagnosis and effective treatment in this case of cerebral falciparum
      malaria--another of medicine's great mimickers.

PMID- 2000527
TI  - Factitious cyclic hypersomnia: a new variant of factitious disorder.
AB  - The central goal of patients with factitious disorders is to receive medical
      care. Unnecessary diagnostic procedures and recurrent hospitalizations often
      ensue. We saw a 39-year-old man with a novel variation of this disorder:
      factitious cyclic hypersomnia, or the simulation of recurrent episodes of
      excessive sleep. This case highlights the observations that patients whose
      illnesses are simulated may have diverse symptoms, that no syndrome is immune to
      factitious imitation, and that attempts at treatment, though exceedingly
      challenging, are always contingent upon appropriate recognition.

PMID- 2000528
TI  - Management of arginine monohydrochloride extravasation in the forearm.
AB  - We initially observed our patient, who had subcutaneous arginine
      monohydrochloride extravasation in the volar forearm, until his wound demarcation
      was complete. After wound demarcation, we proceeded with debridement and partial
      thickness skin grafting. Upper extremity function was totally normal 3 months
      after this therapy. This is the first case report in the literature that
      describes a child with an arginine monohydrochloride-induced extravasation
      necrosis.

PMID- 2000529
TI  - Postanginal sepsis with dysphagia.
AB  - We have described a 10-year-old girl who had dysphagia followed abruptly by
      arthritis. Streptococcus pyogenes was identified as the pathogen by fasciotomy
      with bone biopsy, and a tonsillar fluid collection confirmed the diagnosis of
      postanginal sepsis. The patient was cured by a 6-week course of parenteral
      antibiotics.

PMID- 2000530
TI  - Cerebellar degeneration and Meige's syndrome.
AB  - We have reported a case of Meige's syndrome in a middle-aged man who eventually
      had a cerebellar degeneration syndrome. The extrapyramidal symptoms preceded
      cerebellar signs and symptoms by 5 years. Most patients with idiopathic Meige's
      syndrome show some improvement with high-dose anticholinergic therapy. Our
      patient's lack of response to such agents and his subsequent cerebellar symptoms
      are reminiscent of the situation seen with parkinsonian patients who do not
      respond to medications, indicating a more widespread degenerative disease. The
      association of extrapyramidal symptoms with some spinocerebellar disorders, and
      the pathologic changes seen in the one reported autopsy case, should place the
      group of spinocerebellar disorders high on the differential list.

PMID- 2000531
TI  - A complex ileovaginal fistula with associated obstructive uropathy in a patient
      with Crohn's disease: technical considerations and review of the literature.
AB  - A high index of suspicion of an ileogenital fistula should be aroused by a
      patient with Crohn's disease, weight loss, malnutrition, and a persistent vaginal
      discharge. Preoperative gastrointestinal and genitourinary evaluation should be
      used in an attempt to localize the fistulous origin as well as concomitant
      fistulae. The principles of surgical therapy include preoperative ureteral
      catheters, resection of the diseased bowel and fistulous segment of bowel, and
      interposition of healthy tissue (ie, omentum) between the bowel anastomosis and
      the vaginal cuff.

PMID- 2000532
TI  - Spontaneous rupture of a normal bladder.
AB  - We have reported a case of spontaneous rupture of a normal urinary bladder.
      Patients with this rare condition characteristically have a recent history of
      heavy alcohol intake, sudden onset of abdominal pain coincidental with bloody
      urine, generalized peritonitis, and abnormal renal chemistry. A high index of
      suspicion will lead to early diagnosis and treatment, minimizing the mortality
      attributed to this condition.

PMID- 2000533
TI  - Profound papilledema due to cryptococcal meningitis in acquired immunodeficiency
      syndrome: successful treatment with fluconazole.
AB  - Although cryptococcal meningitis is a frequent infection in patients with AIDS,
      papilledema is rarely reported. We have reported a case of profound papilledema
      associated with cryptococcal meningitis in a patient with AIDS. After treatment
      failure with amphotericin B, the patient was successfully treated with
      fluconazole, and the papilledema resolved.

PMID- 2000534
TI  - A case of neonatal tetanus.
AB  - The morbidity and mortality from neonatal tetanus are preventable. It is largely
      a disease of developing countries. This single case of neonatal tetanus in
      southern Florida must serve as an indicator for the need for health care
      professionals to evaluate the degree of utilization of maternal health services
      and the impact of immunization programs for those women at risk, in this case,
      women who have migrated from developing countries.

PMID- 2000535
TI  - Spontaneous rupture of the stomach in an adult.
AB  - We have reported a case of spontaneous rupture of the stomach in an adult.
      Immediate onset of severe upper abdominal pain after overindulgence in food and
      drink along with radiographic evidence of pneumoperitoneum and the clinical
      findings of massive abdominal distention, epigastric tenderness, shock, and
      occasionally subcutaneous emphysema should suggest the possibility of gastric
      rupture. The treatment is simple, but mortality is high when surgical
      intervention is not rapid.

PMID- 2000536
TI  - Focal hepatic tuberculosis in a patient with acquired immunodeficiency syndrome.
AB  - Patients infected with HIV are known to have unusual manifestations of a variety
      of infections. We have described the third reported case of a patient with AIDS
      having an apparent pyogenic liver abscess subsequently diagnosed as focal hepatic
      tuberculosis. This case emphasizes the need for aggressive diagnostic procedures
      for evaluation of focal liver abnormalities in these patients.

PMID- 2000537
TI  - Benign cystic teratoma manifested as an umbilical hernia.
AB  - We have reported a case of dermoid tumor manifested as an umbilical hernia.
      Resection led to complete recovery.

PMID- 2000538
TI  - Gastric infarction.
AB  - We have described a patient with an acute condition of the abdomen who had
      infarction of the stomach and the small intestine due to atheromatous thrombus of
      celiac and superior mesenteric arteries. We believe this unusual simultaneous
      occurrence of gastric and small intestinal infarction is coincidental. The
      outcome of gastric infarction is frequently fatal.

PMID- 2000539
TI  - Acute oculogyric crisis after administration of prochlorperazine.
AB  - We report a case of acute oculogyric crisis due to prochlorperazine
      administration in a young black woman with a concomitant viral infection.
      Neuroleptic medications are the most common cause of drug-induced acute dystonic
      reactions such as oculogyric crisis. Prochlorperazine is an antiemetic agent with
      a phenothiazine-type chemical structure and is known to cause dystonic reactions.
      Drug-induced acute dystonic reactions are most common in young adults and in men.
      Viral infections may also predispose patients to these adverse reactions. Caution
      is warranted when this drug is used in patients who have other risk factors for
      an acute dystonic reaction.

PMID- 2000540
TI  - Stomatococcus mucilaginosus catheter-related infection in an adolescent with
      osteosarcoma.
AB  - Ours is apparently the first reported pediatric case of Stomatococcus
      mucilaginosus bacteremia. It is the second reported case of S mucilaginosus
      catheter-associated infection, but the first case successfully treated without
      removing the central venous catheter. This unusual organism should be added to
      the list of opportunistic pathogens that can be isolated from immunocompromised
      pediatric patients.

PMID- 2000541
TI  - Indomethacin-enalapril interaction: an alert.

PMID- 2000542
TI  - Nuclear preparedness.

PMID- 2000543
TI  - Cystoscopic adventures.

PMID- 2000544
TI  - The decline in establishment reporting: impact on CWHS industrial and geographic
      data.

PMID- 2000545
TI  - [The effect of the application technic on the formal success of large-field
      radiotherapies].
AB  - 198 patients suffering from Hodgkin's disease or non-Hodgkin's lymphomas were
      irradiated with large-field techniques from 1979 to 1988. 129 of these were
      treated with common block techniques whereas the field-integrated dose
      modification (FIDM) was applied to 69 patients. Retrospective analysis shows that
      FIDM decreases acute toxicity. This was also evident in those patients who were
      irradiated by accelerated hyperfractionation. Although single doses were higher
      in patients treated with FIDM treatment had to be interrupted or abandoned less
      often than in those treated with conventional block techniques. Even high-risk
      patients could be irradiated more consequently.

PMID- 2000546
TI  - [Breast-conserving therapy in breast carcinoma--the indications and sequelae. The
      results of a multidisciplinary consensus meeting].
AB  - A multidisciplinary consensus development conference on the management of breast
      preserving treatment in early breast cancer was organized in November 1989 in
      Berlin. Following a two-day discussion of data presented, conclusions and
      recommendations were achieved on the indication and limitation of breast
      conservation, the optimal technique as well as the diagnostic requirements and
      therapeutic strategies in context with breast conservation including follow-up.

PMID- 2000547
TI  - [Functional microcirculatory disorders in the rat kidney after cobalt-60
      irradiation measured by tissue pO2].
AB  - The left kidneys of Wistar rats were irradiated with a single dose of 20 Gy
      percutaneously and the local tissue partial oxygen saturation was measured with
      the multi wire surface electrode (Kessler and Lubbers). The rats were sacrificed
      at various intervals post irradiation and the pO2-measurements were compared with
      control values from the unirradiated contralateral kidneys in each animal.
      Beforehand "normal histograms" were obtained in unirradiated rats. 24 hours post
      irradiation hyperemia and local perfusion changes were observed, which nearly
      turned to normal in the course of four weeks. The histograms after 16 weeks
      proved persisting damage. After a short delay the nonirradiated right kidneys
      showed similar significant injuries. Further studies are required to clarify
      these alterations. The multi wire surface electrode render it possible to
      conceive early functional disturbances in organ microcirculation after high
      energy irradiation.

PMID- 2000548
TI  - Morphological investigations on the small intestinal mucosa of mouse after mild
      hyperthermic treatment.
AB  - Local hyperthermia, when applied as a therapeutic agent against radio-resistant
      tumours, can result in serious side effects in adjacent non-tumorous tissue, one
      especially thermo-sensitive organ being the small intestine. An experimental
      morphological study was therefore undertaken with mice to investigate whether
      "mild hyperthermia" (41 degrees C for 15, 30 and 60 min) causes alterations at
      the mucosa of the small intestine, and if so what are these effects and their
      likely pathomechanisms. Descriptive light and electron microscopical studies and
      morphometric evaluations are reported on the jejunal mucosa. The observed changes
      were most extensive after 60 min of 41 degrees C hyperthermia; but even 30 and 15
      min hyperthermic treatment was followed by severe degenerative changes. The
      epithelium of the basal crypts and the stromal cells seemed to remain
      morphologically unaffected under these conditions, though the stroma can react
      with a temporary contraction. No "prime event" in the hyperthermia provoked
      tissue changes can be deducted from the combined light, electron microscopical,
      and morphometric studies. Comparing, however, the extent of the effects after
      mild hyperthermia of 60, 30 and 15 min, respectively, four phases of intestinal
      alterations due to mild hyperthermia and a likely pathomechanism of this
      treatment can be defined. The clinical implications of the findings are
      discussed.

PMID- 2000549
TI  - [Iodine-125 seed implantation in the treatment of prostatic carcinoma].
AB  - From February 1981 until August 1984 20 patients (group A) with localized
      prostate cancer were treated by radical pelvic lymphadenectomy and direct 125
      Iodine seed implantation. From September 1984 until January 1988 51 patients
      (group B) underwent a modified diagnostic pelvic lymphadenectomy: four weeks
      later the transperineal seed implantation, guided by rectal ultrasound, followed.
      The follow-up period in group A is 90 months (range 72 to 114), in group B 48
      months (range 30 to 70). Nine patients of group A presented with a progression of
      disease, four died with/of disease. Ten patients of group B developed distant
      metastases, three of them presented with both, distant disease and local
      recurrence: one patient died of disease. The Kaplan-Meier five-year survival
      probability is 82.3% in group A, and 96.5% in group B: the disease-free survival
      62.3% and 75.2% respectively. The probability of local control is 78% in group A
      and 93.5% in group B. In group A there is a higher incidence of complications
      compared to group B, in particular concerning edemas of the legs and the genital
      region. The rate of impotence after seed implantation is very low (2/57 = 3.5%).

PMID- 2000550
TI  - [Cervical carcinoma recurrences and their treatment at the University of
      Freiburg's Women's Clinic from 1976 to 1985].
AB  - From 1976 to 1985 151 recurrent carcinomas of the uterine cervix were diagnosed
      and in 118 cases they have been treated at the Gynaecological Centre of the
      University of Freiburg. The recurrences were divided according to the
      localisation scheme of Munnell and Bonney. 55 patients (47%) received
      radiotherapy, 22 (19%) surgery, 12 (10%) combined therapy of surgery and
      radiotherapy and 13 women (11%) chemotherapy or hormone therapy. 16 patients
      (13%) received a different type of therapy. We found most of the recurrences
      three or four years after the primary therapy. There was no correlation between
      the point of time of diagnosis of the recurrences and the prognosis. The
      distribution of the histology was no parameter for the OAS. The operative
      procedure demonstrates better results than the radiotherapy at recurrences in the
      centre of the pelvis--but there is no significance. The radiotherapy achieves
      significant better results than the operative treatment when we have large
      recurrences in the whole pelvis. If there is an answer of the tumour to the
      therapy, the OAS gets better--in these cases we should use, in spite of the risk
      of more side effects, the whole therapeutic range.

PMID- 2000551
TI  - Hyperthermia and irradiation for locally recurrent previously irradiated breast
      cancer.
AB  - From March 1981 to June 1989, 44 patients with locally recurrent, previously
      irradiated adenocarcinoma of the breast were treated with hyperthermia and
      irradiation. Treatment sites were chest wall (35) or nodal (nine), with an
      average tumor area of 29.44 cm2 (range 0.16 to 252 cm2) prior to treatment.
      Concurrent radiation doses varied from 16 to 56 Gy (mean = 29.4 Gy). Externally
      applied microwave hyperthermia was given twice weekly, aiming at 43 degrees C for
      60 min. Evaluation at one month post treatment revealed 41% complete response
      (CR), 23% partial response (PR), and 36% no response (NR), and 67% of patients
      with a CR sustained that response for greater than 12 months. Tumors heated to a
      mean thermal dose (equivalent-minutes at 42.5 degrees C) greater than 50 had a
      53% CR rate, significantly better than the 14% CR rate observed in patients whose
      tumors received a mean thermal dose less than 50. Among patients with tumors less
      than or equal to 6 cm2 in area, 65% achieved CR, significantly better than the
      26% CR rate noted for patients with tumors greater than 6 cm2 in area. Only four
      patients (7.4%) experienced complications: one developed a catheter-related
      infection, two had ulcerated infections, and one had a severe blister. In
      summary, higher thermal doses delivered and smaller tumor areas were associated
      with more favorable tumor responses.

PMID- 2000552
TI  - [Interstitial Ir-192 afterloading therapy with sequential warm-water
      hyperthermia].
AB  - For selective heating of superficially located or easily accessible tumors
      interstitial hyperthermia has become an increasing popular method in combination
      with interstitial radioactive implants. At our institution the hyperthermia
      treatment is performed utilizing the warm water system KHS-9, which is adapted to
      our Ir-192 high-dose-rate afterloading device, so that the same hollow needles
      for the interstitial radiation can be used for the heating procedure. So far,
      this technique has been applied for the treatment of primary and carcinomas,
      gynecological recurrences, and metastases of malignant melanomas after preceding
      in vitro measurements of temperature distribution. As a result both, in vitro and
      in vivo investigations showed good homogeneity of the temperature throughout the
      heated volume. Analysing the temperature data of in vivo measurements the maximum
      deviation of temperature was found to be 1.5 degrees C. When using a needle
      spacing of 8 mm, the temperature required for clinical application (42.5 degrees
      C) could be maintained in all heat treatments with a preselected water
      temperature of 46 degrees C to 49.5 degrees C.

PMID- 2000553
TI  - Management of soft tissue sarcomas of the extremities.
AB  - The management of soft tissue sarcomas has undergone and continues to undergo
      important changes. The purpose of this report is to review the presentation,
      diagnosis, and natural history of soft tissue sarcomas. In so doing, the
      importance of a careful and rigorous method of evaluation will be emphasized.
      Furthermore, the results of multidisciplinary treatment, with a goal towards limb
      salvage, will be reviewed. With appropriate and timely intervention, selected
      patients with pulmonary metastases may still experience long-term survival.
      Throughout this review, the importance of early and continuing multidisciplinary
      treatment and evaluation will be emphasized.

PMID- 2000554
TI  - The value of routine preoperative laboratory testing in predicting postoperative
      complications: a multivariate analysis.
AB  - The purpose of this study was to evaluate the ability of preoperative laboratory
      testing to predict postoperative complications. Five hundred twenty patients
      undergoing elective surgery had their American Society of Anesthesiologists'
      classification, ponderal index, electrolyte values, glucose levels, blood urea
      nitrogen/creatinine values, complete blood counts, coagulation studies, total
      protein/albumin/lymphocyte count, electrocardiogram, chest radiograph,
      urinalysis, pulmonary function tests, type of anesthesia, and type of operation
      recorded preoperatively. Patients were followed prospectively after surgery for
      the development of complications. The data were analyzed by univariate and
      multivariate methods. Postoperative complications were strongly associated with
      American Society of Anesthesiologists' classification, type of anesthesia, and
      type of operation. However, only a few laboratory tests, such as
      electrocardiogram, chest radiograph, and nutritional status, were associated with
      postoperative complications. Therefore, in general, preoperative laboratory
      testing should only be undertaken for specific indications. Recommendations for
      routine tests are made depending on the age of the patient.

PMID- 2000555
TI  - Elective resection of 332 abdominal aortic aneurysms in a southern West Virginia
      community during a recent five-year period.
AB  - This study analyzed 33 variables that might potentially affect outcome in a
      series of 332 consecutive elective abdominal aortic aneurysm repairs in a
      southern West Virginia community. One of the interesting features of this series
      was that the repairs were done by 22 surgeons with varying degrees of experience.
      The mortality and complication rates were compared for various potential risk
      factors by both univariant methods (chi 2, Fisher's exact, and Student t tests)
      and multivariant methods of analysis. Our early mortality (2.1%) and
      postoperative complication rates were consistent with those of other series. With
      multiple linear regression models, five factors were selected as significant
      independent risk factors associated with an increasing number of postoperative
      complications: the number of blood transfusions (p less than 0.0001), left renal
      vein ligation (p less than 0.0001), the presence of greater than 50% renal artery
      stenosis (p = 0.0012), the lesser experience of the surgeon (p = 0.0203), and the
      history of prior cardiac catheterization (p = 0.0245). The only factor
      statistically correlated with mortality rate was an increased number of
      postoperative complications (p less than 0.0001). Neither postoperative
      complications nor mortality rate was found to be significant and independently
      influenced by other demographic, clinical, or operative factors. It is tempting
      to speculate that surgeons with less experience might be well served to refer
      patients with significant renal artery stenosis and coronary artery disease. Our
      mortality and complication rates were not increased by performing preoperative
      angiography and therefore prudent surgeons may find this helpful in selecting
      patients for safer repair.

PMID- 2000556
TI  - Bacteriologic quality of intraoperative autotransfusion.
AB  - Controversies remain about the bacteriologic aspects of intraoperative blood
      salvage despite the widespread use of this technique. In this prospective study,
      intraoperative salvaged blood was cultured in 401 patients, according to a direct
      plating technique. Bacterial growth was detected in 12.7% of cases. These results
      were compared with those obtained in control studies with sterile water and blood
      bank units under the same culture conditions. Most microorganisms were coagulase
      negative staphylococci, followed by other skin and environmental contaminants.
      Quantitative estimates of contaminations showed low counts of colony-forming
      units (CFU/ml): 82% of positive cultures yielded 1 or 2 CFU/ml and 6% had 5 to 20
      CFU/ml. Patients were followed up for a minimum of 3 months to detect septic
      complications. No statistically significant correlation could be found between
      bacteriologic results of autotransfused blood and infectious complications. This
      study suggests that bacteriologic monitoring of patients who have undergone
      autotransfusion may help in detecting surgical field contamination. It also
      confirms that intraoperative autotransfusion adds little septic risk to cardiac
      surgery.

PMID- 2000557
TI  - Late arterial hemorrhage secondary to a Greenfield filter requiring operative
      intervention.
AB  - Retroperitoneal hematomas associated with Greenfield filters have been described
      and are generally characterized as clinically insignificant. We report a
      retroperitoneal hematoma that was associated with a Greenfield filter and that
      required operative intervention because of hemodynamic instability. At operation
      a lumbar arterial laceration apparently caused by a protruding filter prong was
      identified and ligated. The implications of this occurrence for filter placement
      indications are discussed. The potential life-threatening severity of filter
      associated hematomas is emphasized.

PMID- 2000558
TI  - Bacterial translocation from the gut impairs systemic immunity.
AB  - The goal of this study was to determine the influence of bacterial translocation
      on systemic immunity, since bacteria and their products play a major role in the
      development and maintenance of the host's immune system. To test this hypothesis,
      we measured the blastogenic response of mononuclear cells harvested from the
      blood, spleen, Peyer's patches, and mesenteric lymph nodes of control and
      Escherichia coli C25 monoassociated mice to a battery of mitogens. The E. coli
      C25 monoassociation model was used because this bacterial translocation model is
      not associated with experimental manipulations that are likely to affect the
      systemic immune system. The mitogenic response of lymphocytes isolated from the
      E. coli C25 monoassociated mice was significantly depressed compared to the
      control groups (p less than 0.01). Since the biologic significance of depressed
      in vitro mitogen responsiveness is difficult to determine, we assessed the
      ability of the mice to control a bacterial challenge using an in vivo
      Staphylococcus aureus abscess model. It appears that the observed changes in
      mitogen responsiveness may be of biologic significance, since the ability of the
      E. coli C25 monoassociated mice to control the injected S. aureus was impaired (p
      less than 0.01). These results suggest that an association exists between
      bacterial translocation and decreased systemic immune responsiveness.

PMID- 2000559
TI  - Effect of hyperdynamic circulatory support on hepatic hemodynamics, oxygen supply
      and demand after massive hepatectomy.
AB  - This study was designed to clarify the effect of hyperdynamic circulatory support
      with dobutamine or dopamine after massive hepatectomy on hepatic hemodynamics,
      oxygen supply and demand, and lactate uptake. Mongrel dogs were allocated three
      groups: 70% hepatectomy group; a group that received dobutamine after 70%
      hepatectomy; and a group that received dopamine after 70% hepatectomy. Hepatic
      blood flow and oxygen delivery to the liver decreased after 70% hepatectomy.
      Although oxygen consumption in the liver also decreased, oxygen consumption per
      liver weight increased after massive hepatectomy; an increase of oxygen uptake
      ratio and a decrease of lactate uptake in the liver were observed. When
      dobutamine or dopamine were administered after 70% hepatectomy, hepatic blood
      flow increased, followed by normalization of the balance of oxygen supply and
      demand in the liver; lactate uptake subsequently improved in the liver. The data
      support the conclusion that hepatic oxygen consumption affected by dopamine and
      dobutamine is associated with an increase in the extraction of lactate.
      Hyperdynamic hepatic circulatory support was advantageous to hemodynamics and
      metabolism in the residual liver after massive hepatectomy.

PMID- 2000560
TI  - Continued experience with intraoperative angioscopy for monitoring infrainguinal
      bypass grafting.
AB  - Intraoperative angioscopy provides direct, in vivo, three-dimensional
      visualization of the interior of the blood vessels and grafts. We have shown
      previously that with the application of the basic principles of irrigation and
      with a dedicated irrigation pump that routine intraoperative angioscopy can be
      performed with consistent high quality results during lower extremity
      revascularization. In our total experience with angioscopy as a monitoring
      procedure during infrainguinal bypass grafting, 259 intraoperative angioscopies,
      during 63 femoropopliteal and 196 distal bypass grafts, were performed from May
      1, 1987, to October 31, 1989. Mean total irrigation fluid used in the study was
      448 ml (range, 0 to 1400 ml) with good visual quality in more than 80% of the
      studies. The overall failure rate was 1.5%. No complications were directly
      attributable to the insertion of the angioscope or the use of the pump. Based on
      the angioscopic findings, 124 clinical or surgical decisions were made in 259 of
      the angioscopies. The incidence of graft failure in this study was 8.1% (less
      than 30 days) and 4.8% (greater than 30 days) with a mean follow-up of 272 days.
      Direct inspection of the interior of the graft and native vessels at the time of
      surgery has resulted in the recognition of previously unsuspected vein-graft
      pathology. Angioscopy as the sole monitoring procedure for infrainguinal bypass
      grafting is safe, effective, and reliable and may not only improve the durability
      of these grafts but may improve our understanding of the pathogenesis of graft
      failure and of the progression of the underlying atherosclerotic disease.

PMID- 2000561
TI  - The effect of cholecystokinin-receptor antagonists on cholecystokinin-stimulated
      bile flow in dogs.
AB  - Cholecystokinin is a choleretic in dogs. Some of the effects of cholecystokinin
      in stimulating bile flow in dogs are produced by cholecystokinin stimulating the
      release of other choleretic hormones such as insulin and glucagon. The purpose of
      this study was to determine the effects of cholecystokinin receptor antagonists
      on canine hepatic bile flow and insulin and glucagon release from the pancreas.
      Cholecystokinin octapeptide (CCK-8) and intraduodenal fat were administered to
      dogs that had undergone cholecystectomy with chronic biliary fistulas with and
      without the administration of cholecystokinin receptor antagonists. Bile
      secretion and systemic venous insulin, glucagon, and cholecystokinin levels were
      measured. The cholecystokinin receptor antagonists benzotript and CR 1409 had no
      effect on bile flow or hormone levels when administered without cholecystokinin,
      whereas proglumide produced a large increase in bile flow without altering
      hormone levels. The response produced by proglumide may be the result of an
      osmotic effect produced by the substance being secreted in bile and its
      stimulating bile salt secretion in bile. CCK-8 and intraduodenal fat increased
      bile flow, bile chloride secretion, and cholecystokinin, insulin, and glucagon
      concentrations in venous blood. The cholecystokinin receptor antagonists
      benzotript and CR 1409 significantly decreased the bile flow and insulin and
      glucagon changes produced by exogenous CCK-8. The effect of intraduodenal fat on
      bile flow was not inhibited by the cholecystokinin receptor antagonists, whereas
      the increased insulin and glucagon levels were decreased significantly.
      Intraduodenal fat may release other choleretic hormones not affected by
      cholecystokinin receptor antagonists. The choleresis produced by exogenous CCK-8
      is inhibited by cholecystokinin receptor antagonists, perhaps by inhibiting the
      release of the choleretic hormones insulin and glucagon.

PMID- 2000562
TI  - Effects of hypovolemia and transfusion on tumor growth in MCA-tumor-bearing rats.
AB  - Pretransplant blood transfusion has been shown to significantly affect the
      outcome of renal transplantation. Evidence regarding the association of blood
      transfusions with growth or recurrence of solid tumors is still conflicting both
      in clinical and in experimental studies, although diminished survival has been
      suggested in several studies. To determine the influence of blood transfusions
      and hypovolemia, as separate or combined factors, on tumor growth, we evaluated
      the weight of a subcutaneously implanted sarcoma (methylcholanthrene-induced) in
      35 rats. After reaching 1% tumor burden (day 0), the animals were separated into
      two groups: hypovolemia (shed volume, 15 ml/kg) or normovolemia. These groups
      were further divided according to resuscitation: OO (no resuscitation), BL
      (receiving syngeneic blood stored in citrate phosphate dextrose for 4 days, 15
      ml/kg), SL (receiving 0.9% sodium chloride, 45 ml/kg). Tumor dimensions were
      determined daily by external measurement, and tumor weight was calculated.
      Hypovolemia exerted a significant influence on tumor growth, independent of the
      resuscitation modality. The rats that received blood transfusions showed an
      increased rate of tumor growth, compared to the animals that received saline
      solution or no treatment. No interaction was noted between the effects produced
      by hypovolemia and blood transfusion. We conclude that the hypovolemic event
      enhanced tumor growth independently of the resuscitation, and transfusion of
      citrate phosphate dextrose-blood stored for 4 days did influence tumor growth in
      this model. We suggest that the effect of blood transfusion in patients with
      cancer has to be redefined to account for the influence of possible hypovolemic
      events.

PMID- 2000563
TI  - Extracellular matrix preparation of expanded polytetrafluoroethylene grafts
      seeded with endothelial cells: influence on early platelet deposition, cellular
      growth, and luminal prostacyclin release.
AB  - The importance of blood and extracellular matrix precoating of expanded
      polytetrafluoroethylene (ePTFE) grafts on the effectiveness of endothelial cell
      (EC) seeding was assessed in a canine experimental model. Part I of the study
      documented ex vivo platelet deposition in 256 ePTFE grafts, 6 cm x 4 mm internal
      diameter, after implantation as femoral artery-femoral vein or carotid artery
      jugular vein arteriovenous shunts. These conduits were precoated with blood,
      fibronectin, laminin, or collagen type IV with laminin, after which they were
      seeded with enzymatically derived and cultivated venous canine endothelium at a
      density of 30,000 to 40,000 EC/cm2 of graft surface. Luminal deposition of Indium
      111-labeled platelets, expressed as 10(8) platelets/cm2, at 30 minutes (n = 176)
      and 24 hours (n = 80), respectively, was 2.29 and 0.30 for blood, 2.83 and 0.37
      for fibronectin, 0.99 and 0.08 for laminin, and 0.98 and 0.11 for collagen type
      IV with laminin. Part II of the study documented in vivo luminal EC coverage at
      14 days of 6 cm x 4 mm internal diameter ePTFE femoral or carotid arterial grafts
      (n = 8) prepared in the same manner as part I ex vivo shunt grafts. EC coverage
      with blood, fibronectin, laminin, and collagen type IV with laminin preparation
      was 42%, 49%, 44%, and 52%, respectively. The graft:carotid artery ratio of
      luminal 6-keto-PGF1 alpha release at 14 days with these same four preparations
      was 0.38, 0.31, 0.35, and 0.32, respectively. Precoatings of ePTFE prostheses
      with fibronectin, laminin, and collagen type IV are known to enhance the initial
      attachment of seeded EC. Fibronectin caused an insignificant increase in early
      platelet accumulation; laminin or laminin with collagen type IV preparations were
      associated with significantly less (p less than 0.005) deposition of platelets
      when compared to whole blood preparations. Most importantly, none of the four
      preparation techniques resulted in different in vivo rates of EC growth or
      luminal release of prostacyclin from conduits studied 14 days after implantation.

PMID- 2000564
TI  - Cystic dilatation of the cystic duct: a new type of biliary cyst.
AB  - A case of a patient with a congenital cyst that was localized solely to the
      cystic duct is presented. We propose including this anomaly in the biliary cyst
      classifications, which currently include choledochal and intrahepatic and
      extrahepatic biliary cysts. The diagnosis and management of this new type of cyst
      in addition to other types of biliary cysts are discussed.

PMID- 2000565
TI  - Inflammatory pseudotumor of the liver.
AB  - Inflammatory pseudotumor of the liver is an extremely rare entity. Because of its
      unusual clinical presentation and confusing histologic picture, a diagnosis of
      malignancy is frequently made. Thus the surgeon is closely involved with the case
      and extensive procedures are not uncommon. However, this lesion is benign and
      will even regress spontaneously, making radical surgical procedures
      contraindicated. The difficulty lies in establishing an accurate diagnosis and
      the histologic pitfalls of this particular process. Conservative therapy can then
      be applied, avoiding surgical morbidity.

PMID- 2000566
TI  - Congenital cyst of common bile duct: an unusual cause of obstructive jaundice.
AB  - Congenital cysts, sometimes referred to as nonparasitic biliary cysts, are not
      unusual findings in the liver parenchyma, but they have not been previously
      described in the common bile duct. This clinical report describes a 41-year-old
      woman with obstructive jaundice that was caused by congenital cysts. The patient
      had obstruction of the middle portion of the common bile duct; therefore the
      major differential diagnostic considerations were cholangiocarcinoma, cancer of
      the pancreas, or true biliary cysts. Congenital cysts, retention cysts, and
      neoplastic cysts cannot be differentiated from other true cysts preoperatively.
      Diagnosis can only be established by microscopic examination after surgical
      excision.

PMID- 2000567
TI  - Isolated subclavian artery dissection after blunt trauma.
AB  - We present a case report of a patient with an isolated dissection of the
      subclavian artery after blunt trauma. The patient who was admitted to our center
      after a motor vehicle accident, complained of chest and neck pain and physical
      findings of diminished left extremity pulses. Arteriography showed an occluded
      subclavian artery with the possibility of a dissection. The dissection was
      confirmed at surgery with the proximal extent originating just distal to the
      origin of the vertebral artery. The distal extent of the dissection was not
      determined. Operative repair was performed by a carotid-to-subclavian artery
      bypass obliterating the false lumen of the dissection with a running vascular
      anastomosis. The patient, who was discharged 5 days after repair, had normal
      extremity neurovascular function at 4 months follow-up.

PMID- 2000568
TI  - Contrast material in bowel obstruction.

PMID- 2000569
TI  - The role of contrast radiology in small-bowel obstruction.

PMID- 2000570
TI  - Concerning repeat hepatic resections for colorectal metastases.

PMID- 2000572
TI  - [A national database for information on disease prevention and health promotion
      in USA].

PMID- 2000571
TI  - Location of vein patch for carotid endarterectomy.

PMID- 2000573
TI  - [Intraosseous infusion].

PMID- 2000574
TI  - [Reflections on the scientific and organizational development of internal
      medicine].

PMID- 2000575
TI  - [Health for all--utopia or reality?].

PMID- 2000576
TI  - [Business in medicine].

PMID- 2000577
TI  - [Is antihypertensive treatment more dangerous than presumed?].

PMID- 2000578
TI  - [Telecommunications in Norwegian medicine].

PMID- 2000579
TI  - [Use of telecommunications in pathology and anatomy services].
AB  - Telepathology comprises the transmission of microscopic images via the
      telecommunications network. This paper describes the first experiences from this
      new technology in Norway. These include teleconferences based on showing
      histologic slides from the Department of Pathology at the University Hospital in
      Tromso to clinicians at local hospitals. A frozen section service to Kirkenes
      Hospital, based on remote control of a robotic microscope and transmission of
      high quality video images of the slide, has also been successfully established.

PMID- 2000580
TI  - [Distance diagnosis of skin diseases].
AB  - During a period of eight weeks in late 1989, doctors in general practice in
      Kirkenes brought 27 dermatological patients to a studio at the local hospital.
      Video images were transmitted via a two-way telephone and video network, which
      enabled the patient and the doctor in Kirkenes to consult a specialist in
      dermatology in Tromso. All the patients received written information before the
      consultation. Anamnestic information and clinical manifestations were presented
      from the studio at Kirkenes sykehus. The dermatologist diagnosed the disease and
      prescribed treatment from the studio at the hospital in Tromso. The technical
      equipment satisfied our demands for remote diagnostics in dermatology. All the
      patients were positive to remote consultations.

PMID- 2000581
TI  - [Testing of a simple information program to improve elderly patients' knowledge
      about their medication].
AB  - The programme, which was provided as a supplement to the standard information on
      the patient's medication upon discharge from hospital, consisted of oral
      information about which drugs to use and how to take them, a medication card, and
      one page of general information on how to take drugs. The programme was tested in
      an open, controlled manner in 24 test and 23 control patients, mean age 80 years.
      The results revealed that the patients' knowledge about their medication was
      generally good at follow-up four weeks later. The test group achieved a
      significantly higher score on questions about the technique for taking oral
      medication and why this is important. It is concluded that this type of
      information should be supplied when elderly patients are discharged from
      hospital.

PMID- 2000582
TI  - [Information and rehabilitation after myocardial infarction. A model from the
      Aust-Agder central hospital].
AB  - At Aust-Agder Sentralsjukehus, with a catchment population of 95,000, an
      information programme has been developed for patients with myocardial infarction
      and for patients undergoing coronary bypass surgery or PTCA. The authors also
      discuss the rehabilitation programme for these patients after discharge from
      hospital.

PMID- 2000583
TI  - [Cholesterol level among school children. Cholesterol measurements in adolescents
      in a municipality in Finnmark and a municipality in Sogn and Fjordane].
AB  - This article reports a survey conducted to measured serum cholesterol in pupils
      aged 13-16 years in a municipality in the county of Finnmark and in a
      municipality in the county of Sogn og Fjordane. Cholesterol levels were analysed
      and information was collected by questionnaire on eating habits, smoking habits
      and occurrence of cardiovascular disease in the family. We did not find any
      differences between the two communities in respect of cholesterol level, nor any
      relationship between eating habits and cholesterol level. Pupils with parents
      and/or grandparents with cardiovascular disease had a significantly higher
      cholesterol level than pupils with no such disease in their family.

PMID- 2000584
TI  - [Consequences of diagnostics with magnetic tomography].
AB  - Physicians referring patients to examinations by magnetic resonance tomography
      (MT) were asked to answer almost identical questionnaires before and after the
      examination. The questions referred to diagnosis and planned patient management.
      Impact of MT was measured by examining the changes in patient diagnoses and
      planned management after the MT scans. In 33% of the group (400 patients) the
      main diagnosis (four digit ICD-9 code) changed after MT. Diagnostic security was
      better for 43%, and further diagnostic follow-up changed for 56%, surgery for 20%
      and radiation therapy for 11%. MT was assumed to have had real consequences for
      33% of the patients in terms of significant changes in the doctors planned
      management or in his concept of the disease. In a follow-up study 1.5-2 years
      after MT, 64% of the referring doctors were of the opinion that the MT scan had
      had consequences for the patient and they placed the emphasis on less active
      patient follow-up after MT.

PMID- 2000585
TI  - [Therapeutic failure of antineoplastic agents. Extracellular and cellular
      causes].
AB  - Chemotherapy plays an important role in the treatment of cancer. However, the
      drug regimens used today can only offer a cure to a small fraction of cancer
      patients. The article reviews the factors that limit the effect of
      chemotherapeutic treatment of cancer. The major cause of failure of
      chemotherapeutic treatment is the presence of resistant tumour cells. In addition
      to the various changes that may occur in tumour cells, various other factors may
      limit the "effective concentration" of a drug delivered to the site of the
      tumour, and thereby affect the overall clinical response to therapy.

PMID- 2000586
TI  - [Injuries in Rauma municipality in 1983. Therapeutic level and costs].
AB  - In 1983 doctors engaged in primary health care recorded all accidents leading to
      contact with a doctor. It was found that 9.1% of the total population consulted a
      doctor because of an accident. Of this percentage, 80.6% were treated by the
      local doctor, 13.7% were treated as outpatients at the local hospital, and 5.7%
      were admitted to hospital. The mean cost of the accidents was estimated to be NOK
      1,901 (in 1983 prices, or NOK 2,841 in 1990 prices). 51% of the costs referred to
      sick pay, and 29% to hospital costs. Accidents at work accounted for 39% of the
      costs, traffic accidents 24% and accidents in the home 27%. We conclude that
      accidents in the home, and at school, and injuries from sports, are fields where
      accident prevention campaigns should be started as part of primary health care.

PMID- 2000587
TI  - [Pseudotumor cerebri].
AB  - Pseudotumor was diagnosed in six patients aged three to 38 years during an eight
      year period. The diagnosis was based on headache, choked disks and normal
      cerebrospinal fluid and CT scans. Other symptoms were visual impairment, VIth
      nerve palsy and ataxia. Sagital sinus trombosis was excluded by angiography or
      magnetic resonance imaging. Pharmacological treatment with digitoxin,
      acetazolamide, furosemide or corticisteroids reversed clinical symptoms and signs
      in two patients. In the other four, shunt surgery with cerebrospinal fluid
      diversion to the right atrium or the peritoneal cavity rapidly reversed clinical
      symptoms and signs.

PMID- 2000588
TI  - [Horner's syndrome. With special reference to topographical diagnosis].
AB  - The triad miosis, ptosis and hemifacial anhidrosis make up the well-known
      Horner's syndrome. This is caused by a lesion or a dysfunction in the
      "oculosympathetic pathway" running from the hypothalamus to the eye. Various
      disease entities may manifest themselves in this way, and it is important to be
      able to determine whether the dysfunction is localized to the central,
      preganglionic or postganglionic neurone. This review presents the various tests
      used for this purpose, describes our recent contributions in the field, and
      finally proposes a simple scheme that is suitable for topographical diagnosis.

PMID- 2000589
TI  - [The role of complement system in infections].
AB  - The complement system plays an important role in host defence against infection,
      which includes localization and destruction of microorganisms. However, in the
      course of evolution pathogenic microorganisms have evolved mechanisms to escape
      complement attack. Furthermore, pathogenic microorganisms may mimic human
      complement proteins and use complement activation as a prerequisite for
      infectivity. This review focusses on the complex and often paradoxical role of
      the complement system in host defence against infection.

PMID- 2000590
TI  - [Non-Hodgkin's lymphoma in the gastrointestinal tract].
AB  - The gastrointestinal tract is the predominant site of extranodal non-Hodgkin's
      lymphoma. We present a summary of our recommendations as regards treatment. To
      avoid serious complications, such as perforation and/or bleeding, surgical
      resection should be considered before chemotherapy or radiation therapy. The
      laparotomy gives an opportunity to perform an exact staging procedure, including
      biopsy from the primary site and the lymph nodes. We recommend that
      gastrointestinal malignant lymphomas should be referred to medical centers with
      special competence in this field.

PMID- 2000591
TI  - [Blood cultures in general practice. Suspected meningococcal disease and other
      serious infections with bacteremia].

PMID- 2000592
TI  - [Vitamin B 12 deficiency in strict vegetarian diet. Why do some people choose
      such a diet, and what will they do in case of vitamin B 12 deficiency].
AB  - Nine persons in the county of Troms, Norway, were interviewed on their strict
      vegetarian diet. Improved health was indicated as the main reason for their
      choice of diet, but religion was a contributing reason for some. Most of the
      study persons would increase the intake of vitamin B12 if a deficiency state were
      to occur. One person reported, however, that she would not regard vitamin B12
      deficiency as a health problem. The interviews disclosed beliefs regarding human
      physiology that are very far removed from standard scientific knowledge. The
      article indicates that communication between patient and the health care system
      may be difficult in such circumstances. Problems of communication would probably
      be minimized if the patient had a thorough understanding of human physiology and
      the health worker a thorough understanding of the reasons for the patient's
      choice of diet.

PMID- 2000593
TI  - [Efficiency analysis of university hospitals].
AB  - The Norwegian Institute for Hospital Research has published several studies on
      hospital running costs. Judging from reports in the media these studies have
      attracted much public interest. It has been maintained that Haukeland sykehus is
      the most efficient regional hospital, while results from both Ulleval sykehus and
      the Rikshospitalet have been poor. In an alternative analysis undertaken in 1988
      the main aim was to analyse medical efficiency, number of admissions, and length
      of stay in every department at all regional hospitals. This study showed great
      variation in the period of hospitalization within the same speciality at
      different hospitals. The Regionsykehuset in Tromso was shown to be the most
      efficient medically, with the shortest period of hospitalization in all
      departments except in the departments of surgery and gynecology. In these cases
      the period of hospitalization was shortest at Ulleval sykehus. Haukeland sykehus
      and the Regionsykehuset in Trondheim both came out at the bottom of the list,
      with consistently the longest period of hospitalization for patients in regional
      hospitals. When the variation in results depend on the methods of evaluation used
      then it is time to stop and think. Are the methods of evaluation inferior to what
      is being evaluated? In which case, it is time to discuss the following question
      what criteria are applicable and of value when comparing hospitals and/or
      departments?

PMID- 2000594
TI  - [Use of estrogens during and after menopause. A statement from a consensus
      conference on the use of estrogens during and after menopause, Soria Moria, Oslo
      27-29 November 1990].

PMID- 2000595
TI  - [Antihypertensive treatment--more dangerous than presumed?].
AB  - The effect of antihypertensive drugs on the incidence and mortality of coronary
      heart disease has been disappointing. One possible reason for this lack of effect
      may be the interaction between the drugs and the lipid metabolism. Norwegian
      studies indicate that other reasons may be that treatment was started on doubtful
      criteria, or that insufficient consideration was given to the whole constellation
      of risk factors in hypertensive subjects. In addition, studies from the National
      Health Screening Service suggest that antihypertensive drugs have an adverse
      effect on risk of incidence and death from coronary disease among patients
      receiving these drugs, even when other risk factors are adjusted for. Therefore
      the lipid theory may not explain the lack of effect of antihypertensive
      treatment. The importance of exercising caution in using all kinds of
      antihypertensive drugs is emphasized.

PMID- 2000596
TI  - [Breast feeding guidelines and breast milk supplementation: physicians are not in
      agreement with the WHO code. My child--a new broschure from Nestle].

PMID- 2000597
TI  - [Bad custom].

PMID- 2000598
TI  - [Selo-Zok--an expensive progress].

PMID- 2000600
TI  - [Therapeutic considerations for children during terminal care].

PMID- 2000599
TI  - [End of the drug monopoly in Norway?].

PMID- 2000601
TI  - [Acute pulmonary failure syndrome in adults].

PMID- 2000602
TI  - [Iron and iron deficiency risk groups].

PMID- 2000603
TI  - [Transplantations, priorities and ethics].

PMID- 2000604
TI  - [Information about ultrasonic examination to pregnant women].

PMID- 2000605
TI  - [Quality assurance of medical technical equipment].

PMID- 2000606
TI  - [Efficiency of health care services--a moral matter].

PMID- 2000607
TI  - [Gambling disease].

PMID- 2000608
TI  - [Results of 6 1/2 years of heart transplantation at Rikshospitalet].
AB  - We discuss our experience from 6 1/2 years of orthotopic heart transplantation at
      Rikshospitalet (the National Hospital). 112 grafts were performed on 109 patients
      (19 women and 90 men), mean age 47 years (range 14-63). In the first nine
      patients the immunosuppressive regimen consisted of cyclosporine A and
      prednisolone, and in the last 100 azathioprine was added (triple medication).
      There was no operative mortality. 21 patients died, giving an 81% cumulative
      survival, with a significantly better prognosis among those who received triple
      immunosuppressive regimen. The main complications were rejection, infection and
      arrhythmia. Since our main problem was rejection it is concluded that careful
      supervision, concentrated on as few cardiologists as possible, and a liberal
      indication for myocardial biopsy, are decisive for the prognosis.

PMID- 2000609
TI  - [Single lung transplantation as treatment of terminal lung diseases].
AB  - The article describes the first cases of single lung transplantation in Norway.
      The indication for surgery was end-stage pulmonary disease (1 sarcoidosis, 2
      emphysema) in three severely disabled patients requiring administration of
      oxygen. The operation necessitated cardiopulmonary bypass in all patients.
      Primary graft function was excellent. Epidural analgesia, peripheral pulse
      oxymetry and continuous monitoring of mixed venous oxygen saturation aided early
      extubation. The initial postoperative course with a four drug immunosuppressive
      regimen has been encouraging. Rejection is monitored by clinical examination,
      chest x-ray, serial pulmonary function tests and transbronchial biopsies.

PMID- 2000610
TI  - [Allogeneic bone marrow transplantation in adults. Results after fractionated
      whole body irradiation and high dosage cyclophosphamide and use of HLA-compatible
      sibling donors].
AB  - We present short and long-term results of allogeneic bone marrow transplantation
      after hyper-fractionated total body irradiation and high dose cyclophosphamide in
      ten patients treated for leukaemia during the period 1985-89. Three patients died
      from complications connected to the transplantation, while seven are living free
      from leukaemia 18 to 59 months after transplantation (mean 41 months). Two
      patients need treatment for chronic graft versus host disease. Allogeneic bone
      marrow transplantation is expensive and risky. Close cooperation between
      clinicians and laboratory specialists is essential. The treatment increases long
      term survival and probably cures certain patients with leukaemia. Some of these
      patients will need treatment for chronic graft versus host disease and other late
      sequelae.

PMID- 2000611
TI  - [New therapeutic possibilities for leukemia in adults. Indications and progress
      measures for allogeneic bone marrow transplantation].
AB  - Marrow ablation with cytotoxic drugs and/or total body irradiation followed by
      allogeneic bone marrow transplantation from an HLA-identical sibling cures many
      patients with acute and chronic myeloid leukaemia. We have obtained good results
      with this treatment. Up to now the necessary funds to cover the minimal
      requirements for transplantations in Norway have not been granted. It is now
      possible to use unrelated, HLA-matched donors, which will more than double the
      need for allogeneic bone marrow transplantations within a few years. This article
      discusses indications, results, costs and practical procedures connected to
      allogeneic bone marrow transplantation for leukaemia in adults.

PMID- 2000612
TI  - [Experiences of pregnant women with ultrasonic examination].
AB  - 655 pregnant women answered a questionnaire after routine ultrasound examination
      around the 17th week of pregnancy. Every second woman received written
      information about ultrasound examination in pregnancy. 37 women answered
      inconsistently and were withdrawn from the study. 435 (70%) women out of 618 were
      satisfied with the information they had received on ultrasound examination in
      pregnancy, although 171 of them had not received our letter of information. Only
      26 out of 290 women who had received the information did not consider it to be
      satisfactory. 252 (40%) admitted being anxious prior to the examination, but we
      found no relation between anxiety and receiving or not receiving the letter. 584
      (95%) answered that they felt more secure after the ultrasound examination and
      609 (99%) were satisfied with the information they had received during the
      examination. All the women wanted to have a routine ultrasound examination during
      a possible subsequent pregnancy.

PMID- 2000613
TI  - [Fulminating hepatitis after treatment with naproxen and/or disulfiram?].
AB  - A 49 year old female was started on disulfiram. Six weeks later she was given
      naproxen because of epicondylitis. After 5 days' treatment with naproxen she
      complained of nausea, anorexia and jaundice. At admission, bilirubin was 452
      mumol/l, aspartate aminotransferase (ASAT) 1925 U/I, alanine aminotransferase
      (ALAT) 2815 U/I and prothrombin time measured as Normotest was 27%. The patient
      developed a fulminant hepatitis and died in hepatic coma almost four weeks after
      the introduction of naproxen. Postmortem examination disclosed a small liver
      (1,100 g) and histological examination showed massive necrosis and collapse of
      the lobules. The naproxen was the most probable cause of death, but it is
      impossible to exclude disulfiram as causative agent.

PMID- 2000614
TI  - [Helicobacter pylori and ulcer disease].
AB  - There is a strong association between Helicobacter pylori and peptic ulcer and
      chronic gastritis. It has been shown, furthermore, that the relapse rate after a
      healed duodenal ulcer is much reduced when the treatment has also eradicated H
      pylori from the antrum ventriculi. We have tried two simple and rapid tests for
      diagnosing H pylori infection on biopsies taken at gastroscopy. We found a
      significantly larger number of cases with H pylori among patients with peptic
      ulcer than among patients with normal gastroscopic findings. Culturing the biopsy
      proved to be successful, even though transport to the laboratory took about 24
      hours. It has been proved simple to diagnose H pylori, but any practical
      implications of this fact remain to be seen.

PMID- 2000615
TI  - [Conservative treatment of ectopic pregnancy].
AB  - During the last decades the incidence of ectopic pregnancy has been steadily
      rising. The chosen therapy has usually been unilateral salpingectomy. Recently,
      different conservative (tube-preserving) treatment-modalities have been
      introduced in clinical practice. We have tried conservative treatment by local
      injection of prostaglandin F2a (total dose 2-4 mg) directly into the tubal
      pregnancy and, if feasible, also into the corpus luteum graviditate. The
      treatment was successful in 13 out of 16 patients. In one patient laparotomia was
      performed because of pain, and revealed a haematoma in fossa Douglasi.
      Reinjection of prostaglandin was necessary in one patient because of rising HCG
      titres. One patient was hospitalized for four days because of nausea and pain.
      The treatment was otherwise successful. The method may be useful as a non
      surgical alternative in haemodynamically stable patients without tubal rupture.
      Further studies are needed to evaluate the outcome in terms of future fertility.

PMID- 2000616
TI  - [Occurrence of recurrence after regression of low-grade dysplasia in vaginal
      cytological smears].
AB  - 329 females with regress of low-grade dysplasia were followed up by annual
      vaginal smears for a maximum of 14 years. 53 developed recurrence of dysplasia.
      The average annual risk of recurrence was greatest 2-4 years after regress, being
      4.3%. The average annual risk of recurrence for those followed up for more than
      ten years was 0.5%. None of the females developed cervical cancer. It is
      concluded that annual controls may prevent females with regress of previous low
      grade dysplasia from developing cancer. After ten years with no further
      dysplasia, the females are recommended to follow the general practice for persons
      without previous dysplasia or cancer.

PMID- 2000617
TI  - [Spontaneous dissection of the internal carotid artery].
AB  - Spontaneous dissection of the internal carotid artery is supposed to be a rare
      condition, but seems to be increasingly diagnosed. The symptoms are protean from
      unilateral headache, Horners syndrome, tinnitus, to cerebral ischemia and
      hemipareses. The condition is of unknown incidence and usually affects previously
      healthy persons. It is nearly always unilateral. The diagnosis is ascertained by
      characteristic angiographical findings. The prognosis depends on the exhibited
      symptoms. Three patients seen during the last year at the Department of Neurology
      at the National Hospital (Rikshospitalet) are presented, together with a brief
      survey of symptomatology, diagnosis, prognosis and treatment.

PMID- 2000618
TI  - [Atlanto-axial rotatory fixation. Current diagnosis in torticollis].
AB  - Atlantoaxial rotatory fixation is a disorder which must be considered in
      persistent torticollis. The disorder occurs mainly in children and young adults.
      The usual etiological factors are traumas or infections of the upper respiratory
      tract, but the onset may also be spontaneous. The pathogenesis of the fixation is
      poorly understood. We describe three patients with atlantoaxial rotatory fixation
      and demonstrate the usefulness of computerized tomography in the diagnosis of
      this condition. We recommend a posterior atlantoaxial fusion if conservative
      treatment fails to reduce the rotatory fixation.

PMID- 2000619
TI  - [Musculoskeletal disorders among employees in building and construction
      industry].
AB  - A questionnaire was distributed to 2,696 employees in the construction industry
      in order to determine the prevalence of subjectively experienced musculoskeletal
      strain in four regions of the body. A total of 40.3% of the employees had pain at
      the time of questioning. The percentage of the employees with complaints
      increases gradually with age, but least for backache. A comparison of different
      age groups of employees in two occupations reveals that carpenters in the age
      group 30-40 years have more than ten times as many musculoskeletal disorders in
      their arms and hands as office workers in the same age group. We presume that
      more than 90% of these disorders are caused by factors in the working
      environment. The author concludes that it is important to continuously collect
      information on musculoskeletal disorders among workers, and analyze all the data
      systematically.

PMID- 2000620
TI  - [Free skin transplantation].

PMID- 2000621
TI  - [Medical expert systems. Developmental activities in the Scandinavian countries].
AB  - Medical expert systems is a term for computer programs which represent and
      structure medical knowledge, and which can supplement or replace man in
      decisionmaking. Several research groups in Denmark, Finland, Norway and Sweden
      are developing such systems. Many of the projects emphasize educational aspects
      and also serve to qualify the participants in the project. The medical expert
      systems are applied to clinical chemistry, neurophysiological testing or
      intensive care. Within this field of medical expert systems there is much
      duplication of activities and too little practical application. Usually the
      systems are developed to be used as functional prototypes and are often not good
      enough or not intended to be used in daily hospital routines. There should be
      good prospects in this field in the near future.

PMID- 2000622
TI  - [Use of personal computers for statistical analyses].
AB  - We report the range in elapsed time for various statistical analyses and for the
      same logistic regression analysis in 23 different personal computers (PCs).
      Without a floating-point coprocessor, the elapsed time increased from ten to 113
      minutes in the same PC. Elapsed time ranged from two to 45 minutes from 80486 to
      8086 PCs with a floating-point coprocessor. The PC equipment we need strongly
      depends on the type and frequency of the statistical analyses we are to perform.
      If a floating-point coprocessor is installed, the 80286/80287 PC family may be
      fast enough for most users.

PMID- 2000623
TI  - [Quality assurance of technical medical equipment. Report from a research
      department].
AB  - Det norske Veritas has been engaged by the Ministry of health and social affairs
      to establish a system to improve the use and maintenance of technical equipment
      in hospitals. The system is being tested in several hospital departments in
      Norway, among them the Department of anaesthesia at the Regional Hospital in
      Trondheim (Regionsykehuset). This article presents preliminary experiences. The
      system is complicated, and the manuals developed by Veritas are of little help to
      users at the clinic. The system would benefit from being made more simple, more
      directly problem oriented and more adjusted to the users' needs.

PMID- 2000624
TI  - [Outpatient clinics. First choice or second choice services?].
AB  - Some factors that characterize and influence the use of outpatient clinics at a
      medium sized somatic hospital have been investigated. The hospital town residents
      consulted the clinic twice as often as the people in municipalities further away.
      Self-referred controls constituted from six to 54% of the patients in the
      different outpatient clinics. The referrals from the primary health care doctors
      in one of the municipalities served by the hospital constituted only 1/10 of all
      attendances by people from this area at the outpatient clinics. Patients should
      be referred back to the primary health service as soon as possible after a
      critical evaluation of the need for specialist care.

PMID- 2000625
TI  - [Perestroika--in medicine too].
AB  - The article criticizes the one-dimensionality of natural science and the one-way
      concept of causality in medicine. The crisis in medical practice and health
      economy is considered in the light of an outdated and rigid health ideology with
      parallels in the "scientific" dogmas that have now been discarded in Eastern
      Europe. In this article we try to point a way out of this unfortunate situation:
      how would a change of paradigm affect clinical practice, health ideology and our
      concept of social policy?

PMID- 2000626
TI  - [Sudden infant death].

PMID- 2000627
TI  - [Our largest ethical problem].

PMID- 2000628
TI  - [Lung damage caused by waxing of skis].

PMID- 2000629
TI  - [Streptococcal infections].

PMID- 2000630
TI  - Toxicity and kinetics of [3H]microcystin-LR in isolated perfused rat livers.
AB  - Isolated rat livers were perfused for 60 min with either 0.3 or 0.5 microgram/ml
      (initial volume, 119 ml) of [3H]microcystin-LR at a constant flow of 10 ml/min in
      a recirculating system. During the 60-min exposure, toxin caused stimulation of
      glycogenolysis, liver engorgement, and cessation of bile flow. Electron
      micrographs of liver showed dilation of bile canaliculi and the space of Disse.
      loss of sinusoidal lining architecture, and decreased hepatocyte intercellular
      contacts. Although hepatocytes did not exhibit overt necrosis, mitochondria were
      hydropic, occasionally encircled by whorls of rough endoplasmic reticulum, and
      desmosomal tonofilaments were decreased on the plasma membrane lateral surface.
      Isolated mitochondria displayed inhibition of state 3 respiration and a 50-60%
      decrease in the respiratory control index, characteristic of hydropism.
      Distribution of radiolabel was 1.7% to bile, 79% to perfusate, and 16% to liver.
      Two to four percent was recovered in perfusate that leaked from the surface of
      the liver. Of the radiolabel found in bile and perfusate, 78 and 100% were
      associated with parent toxin, respectively. The radiolabel in liver, associated
      with the cytosolic fraction (S-100), corresponded to parent toxin (15%) and to a
      more-polar component(s) (85%). The elimination half-life from perfusate was 130
      +/- 10 min (0.5 microgram/ml) and the hepatic extraction ratio 0.07 +/- 0.01.
      Although the calculated hepatic extraction ratio was low, there was a significant
      accumulation of microcystin in the liver. Many toxic effects of microcystin in
      the perfused liver mimicked those observed in the whole animal, suggesting that
      this model can be used as an alternative to whole animals for screening of
      potential therapeutic agents.

PMID- 2000631
TI  - Evaluation of the persistence of hydronephrosis induced in mice following in
      utero and/or lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an extremely potent teratogen in
      mice, inducing structural malformations in the kidney and secondary palate.
      Maternal depots of TCDD, stored primarily in adipose tissue, are mobilized during
      the nursing period. Thus, lactation serves as a significant route of exposure for
      the developing neonate. The objective of this present investigation was to assess
      whether hydronephrosis persisted postnatally, as well as to determine if the
      renal lesion could be induced lactationally. Pregnant C57BL/6N mice were treated
      once by gavage with 0, 3, or 12 micrograms TCDD/kg body wt on Gestation Day (GD)
      6. All dams were allowed to litter, and each litter was standardized at random to
      a size of six pups. Standardized litters were then reciprocally cross-fostered on
      the day of birth. Postnatal Day (PND) 0, resulting in the establishment of four
      experimental groups: pups not exposed by either route, pups exposed only in
      utero, pups exposed only lactationally, and pups exposed by both routes. Pups
      were euthanized at one of two time points, either at weaning (PND 25) or at
      puberty (PND 67). TCDD was not overtly toxic to the dams or neonates with the
      dosing regime used in this study. Hydronephrotic incidence and severity, while
      greatest for pups receiving dual exposure, were essentially the same for pups
      exposed in utero only vs lactationally only. Lactational exposure induced
      hydronephrosis (HN), as well as exacerbated the severity of existing HN which was
      induced in utero. Regardless of the exposure group, the severity of the renal
      lesion was always greater in the right kidney than in the left. There were no sex
      related differences in either the incidence or the severity of HN, nor was there
      any difference in response between PNDs 25 and 67. These data suggest that the
      renal lesion persists from weaning through puberty, despite the cessation of
      exposure. However, the data indicate that partial recovery from HN induced in
      utero occurs during the early postnatal period, as both hydronephrotic incidence
      and severity decreased with increasing age between GD 18 and PND 25. Recovery was
      most pronounced in the left kidney regardless of dose, thus suggesting that the
      ability to recover may in part be dependent upon the extent of renal damage.

PMID- 2000632
TI  - Hydronephrosis in mice exposed to TCDD-contaminated breast milk: identification
      of the peak period of sensitivity and assessment of potential recovery.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent inducer of hydronephrosis
      in both fetal and neonatal mice. A critical period of sensitivity to TCDD could
      not be identified for prenatally induced hydronephrosis since the urinary tract
      appeared equally sensitive throughout organogenesis. To identify the critical
      period of susceptibility for development of lactationally induced hydronephrosis
      in neonatal mice, as well as to characterize the potential for recovery from this
      renal lesion, dose-response and time-course studies were conducted in the
      postnatal period. Pregnant C57BL/6N mice were allowed natural delivery. In the
      dose-response phase of this investigation, mothers were administered 0, 3, 6, or
      12 micrograms TCDD/kg once by gavage on Postnatal Day (PND) 1, 4, 8, or 14, and
      dams and pups were euthanized on PND 26. The kidneys were examined, and
      hydronephrotic severity was scored. The incidence and severity of hydronephrosis
      were significantly increased above controls only following treatment on PND 1 or
      4, while on PND 8 the increase was marginal and pairwise tests were
      nonsignificant. Following treatment of dams on PND 1, the hydronephrotic response
      detected in 26-day-old pups was significantly greater than that for all later
      exposure days. In the time-course study, dams were given a single oral dose of 0
      or 9 micrograms TCDD/kg on PND 1, and mothers and litters were subsequently
      euthanized on PND 7, 13, 19, or 26. Both hydronephrotic incidence and severity
      increased with time to euthanization following treatment on PND 1. Thus with the
      dosing regimen used in this study, recovery does not appear to occur between PNDs
      7 and 26. Sex-related differences were observed, as the hydronephrotic response
      in males was generally greater than in females. In conclusion, the postnatal
      window of sensitivity during which TCDD can induce hydronephrosis is very narrow.
      Nonetheless, the hydronephrotic response induced during this early postnatal time
      is dramatic. Finally, PND 1 is the peak postnatal period of susceptibility for
      development of TCDD-induced hydronephrosis.

PMID- 2000633
TI  - Disposition of perfluorodecanoic acid in male and female rats.
AB  - The elimination, tissue distribution, and metabolism of [1-14C]PFDA were examined
      in male and female rats for 28 days after a single ip dose (9.4 mumol/kg, 5
      mg/kg). A sex difference in the fecal elimination of perfluorodecanoic acid
      (PFDA) was observed with 51 and 24% of the administered 14C being recovered in
      the feces of male and female rats, respectively, by 28 days post-treatment. The
      cumulative excretion of PFDA-derived 14C in the urine in 28 days was less than 5%
      of the administered dose in both sexes. The sex-related difference in the rate of
      fecal elimination resulted in the observed difference in whole body elimination
      t1/2 of PFDA in males (t1/2 = 23 days) and females (t1/2 = 45 days). The liver
      contained the highest concentration of PFDA-derived 14C in both males and
      females, followed by the plasma and kidneys. The heart, fat pads, testes, and
      gastrocnemius muscle of males, and the ovaries of females contained much lower
      concentrations of PFDA. The reason for the high percentage of the ip dose of [1
      14C]PFDA in the liver (53% males and 41% females, 2 hr post-treatment) was
      further examined using an in situ nonrecirculating liver perfusion technique. It
      was shown that approximately 25% of the [14C]PFDA in the perfusate was extracted
      by the liver in a single pass. The basis for the sex difference in fecal
      elimination of PFDA does not appear to be due to a sex difference in biliary
      excretion. In a 6-hr period, male and female rats with kidneys ligated eliminated
      essentially the same percentage dose of [14C]PFDA into bile. We had hypothesized
      that the persistence of PFDA in rats was due to formation of a PFDA-containing
      lipid (i.e., a [14C]PFDA-containing mono-, di-, or triacylglycerol, cholesteryl
      ester, methyl ester, or phospholipid). However, no evidence that PFDA is
      conjugated to form persistent hybrid lipids was obtained, nor were polar
      metabolites of PFDA detected in urine or bile. In addition, daily urinary
      excretion of fluoride in male and female rats before and after PFDA treatment was
      similar, suggesting that the parent compound is not defluorinated. Thus, the
      disposition of PFDA in male and female rats is characterized by an apparent lack
      of biotransformation.

PMID- 2000634
TI  - Phosphoramide mustard is responsible for the ovarian toxicity of
      cyclophosphamide.
AB  - Although cyclophosphamide (CPA) is an ovarian toxicant, the responsible
      metabolite(s) have not been identified. The purpose of these experiments was to
      determine if phosphoramide mustard or acrolein were the proximate toxicants
      produced by metabolic activation of CPA. To do this analogs of CPA known to
      generate either phosphoramide mustard or acrolein in vivo were assessed for their
      ability to produce ovarian toxicity as measured by differential follicle
      destruction, ovarian volume loss, and uterine weight loss and compared to the
      effects produced by CPA. Phosphoramide mustard cyclohexylamine salt (PMC) and
      trans-4-phenylcyclophosphamide (T4P), both of which generate phosphoramide
      mustard, and didechlorocyclophosphamide (DCPA) and allyl alcohol (AA) which
      generate acrolein were administered ip to female C57BL/6N mice, 10-12 weeks old,
      at doses equimolar to 0, 25, 75, 200, or 500 mg/kg of CPA. Three days later the
      animals were killed, their uterine weights measured and their ovaries removed,
      fixed, and serially sectioned. Only PMC and T4P produced ovarian toxicity. On an
      equimolar basis these compounds were over twice as potent as CPA. Both caused a
      significant reduction in uterine weight (to 50% of controls) at doses of 200
      (PMC) and 150 mg/kg (T4P). PMC and T4P also caused a 50% reduction in ovarian
      volume at doses above 75 mg/kg. Primordial follicles were most sensitive; ED50s
      were 76.9, 25.3, and 19.3 mg/kg (0.276, 0.091, and 0.069 mmol/kg) for CPA, PMC,
      and T4P, respectively. Growing follicle numbers were also reduced by T4P and PMC,
      an effect not seen with CPA treatment. Finally, antral follicles were
      significantly reduced by all doses of PMC, and with T4P at doses greater than 75
      mg/kg. The highest doses of PMC, T4P, and CPA all caused a reduction in antral
      follicle numbers to less than one percent of controls. Didechlorocyclophosphamide
      (DCPA) and allyl alcohol (AA), compounds that generate acrolein but not
      phosphoramide mustard in vivo, had no effect on any of the parameters measured
      even when injected directly into the ovary. This suggests that phosphoramide
      mustard is responsible for CPA ovarian toxicity. The greater potency of PMC and
      T4P compared to CPA is likely the result of these compounds bypassing important
      detoxification steps, therefore, more of the parent compound reaches the ovary as
      the toxic metabolite.

PMID- 2000635
TI  - Gastrointestinal absorption of paraquat in the isolated mucosa of the rat.
AB  - The gastrointestinal absorption of paraquat (1,1'-dimethyl-4,4'-bipyridylium) was
      studied using the isolated mucosa from different regions of the gastrointestinal
      tract of rats. Tissues were stripped of their muscle layers and the viability of
      the mucosa was maintained in flux chambers by bathing both serosal and luminal
      membranes with separate oxygenated solutions. Paraquat absorption, transmucosal
      potential difference (PD), and permeability of the mucosa were studied. Exposure
      of the luminal side of isolated mucosae to paraquat (100 mg/ml) resulted in
      greater paraquat absorption across the small intestine compared to other regions
      of the gastrointestinal tract. The descending order of tissue absorption (as
      %/cm2 mucosa) was jejunum (17.6 +/- 0.8%), ileum (10 +/- 2.7%), colon (5.7 +/-
      3.2%), duodenum (5.5 +/- 1.3%), stomach (2 +/- 0.8%), and esophagus (0.5 +/-
      0.7%). Mucosal uptake of paraquat in the ileum was nonlinear over a luminal
      concentration range 2-200 mg/ml. Three phases to paraquat absorption were
      identified in this region of the small intestine: (i) a rate which was faster
      than diffusion (2-20 mg/ml paraquat); (ii) a rate which was slower than diffusion
      and obeyed saturation kinetics, with an apparent Km = 116 mM and Vmax = 11.3
      mumol/g/hr, at paraquat concentrations up to 150 mg/ml: and (iii) a rate similar
      to that of diffusion at 200 mg/ml paraquat. Paraquat absorption at 200 mg/ml was
      also associated with an increase in mucosal permeability and reduction in PD.
      Inhibition of tissue metabolism resulted in a linear or diffusional paraquat
      absorption over a wide luminal concentration range (2-200 mg/ml). It is
      suggested, therefore, that paraquat absorption in the rat occurs principally in
      the small intestine and by a mechanism which consists of facilitated, saturable,
      and diffusional components. Knowledge of the mechanism by which paraquat gains
      entry to the bloodstream may offer new approaches to the development of safer
      formulations of the herbicide.

PMID- 2000636
TI  - Disposition of inhaled isoprene in B6C3F1 mice.
AB  - Isoprene (2-methyl-1,3-butadiene) is the monomeric unit of widely occurring
      natural products called terpenes. Isoprene is widely used in industry with nearly
      1.1 million pounds produced in the United States in 1987. The purpose of this
      investigation was to determine the toxicokinetics of inhaled isoprene in B6C3F1
      mice and to compare the data to previously published toxicokinetic data in F344
      rats (A. R. Dahl, L. S. Birnbaum, J. A. Bond, P. G. Gervasi, and R. F. Henderson,
      1987. Toxicol. Appl. Pharmacol. 89, 237-248). The comparative toxicokinetics in
      the two species will be useful for extrapolation of rodent toxicity data to
      humans. Male B6C3F1 mice were exposed to nominal concentrations of 20, 200, and
      2000 ppm isoprene or [14C]isoprene for up to 6 hr. For all exposures, steady
      state levels of isoprene were reached rapidly (i.e., within 15 to 30 min) after
      the onset of exposure. The mean (+/- SE) steady-state blood levels of isoprene
      (identified by headspace analysis) for the 20, 200, and 2000 ppm exposures were
      24.8 +/- 3.3, 830 +/- 51, and 6800 +/- 400 ng isoprene/ml blood, respectively. At
      the two higher exposure concentrations, the increases in blood levels of isoprene
      were proportional to the increases in air concentrations of isoprene. There was
      approximately a 2.3-fold decrease in the retained 14C/inhaled 14C ratio with
      increasing exposure concentration. Depending on the exposure concentration, from
      52% (20 ppm isoprene) to 73% (2000 ppm isoprene) of the metabolite-associated
      (nonisoprene) radioactivity was excreted in the urine over a 64-hr postexposure
      period. 14CO2 exhalation after the end of the 6-hr exposure was minimal (2%) at
      the 20 ppm exposure and increased up to 18% at the higher isoprene exposure
      concentrations. These data suggest that metabolism of isoprene in mice is
      nonlinear within the range of exposure concentrations used in this study.
      Hemoglobin adduct formation reached near-maximum between 200 and 2000 ppm
      isoprene exposure concentration, consistent with our conclusion that pathways for
      metabolism of isoprene were saturated. Isoprene metabolites were present in blood
      after inhalation of isoprene at all concentrations studied. There were
      substantial differences in the toxicokinetics of inhaled isoprene in mice
      compared to rats. In mice, fractional retention of inhaled isoprene, which
      reflects, in part, metabolism of isoprene, was linearly related to exposure
      concentrations up to 200 ppm but decreased at 2000 ppm; in rats, fractional
      retention of inhaled isoprene decreased with increasing exposure concentration
      over a range of exposures from 8 to 1500 ppm.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 2000637
TI  - Studies on the age-dependent effects of galactosamine in primary rat hepatocyte
      cultures.
AB  - Galactosamine (GalN) has been known to induce liver injury by depletion of uracil
      nucleotides. The objective of the present work was to examine age-dependent
      toxicity of GalN in primary hepatocyte cultures. Hepatocytes from fetal (Day 20
      of gestation), neonatal (2.5-day), adult (5-month), and aged (30-month) rats were
      established as monolayered cultures. LDH leakage, cell viability, UTP, UDP, and
      UMP were measured as end points of toxicity in cultures exposed to 5 mM GalN. LDH
      leakage was increased and cell viability was decreased in adult rat hepatocytes
      at 48 and 60 hr after treatment. Although similar effects were observed in
      hepatocytes from aged rats, these cells appeared resilient to GalN toxicity as
      indicated by significantly less LDH leakage and cell death. Fetal and neonatal
      rat hepatocytes also exhibited greater resiliency to GalN based on the same end
      points. The UTP, UDP, and UMP levels of aged hepatocytes (30-month) were higher
      than control adult levels to begin with and dropped after GalN treatment. The
      level of UMP at 60 hr was similar to that of normal adult cells, but the UTP and
      UDP levels were significantly higher in aged hepatocytes in comparison to those
      of adult hepatocytes. The levels of uracil nucleotides in the fetal and neonatal
      cells were the same as those in adult cells, but did not decrease significantly
      after exposure to GalN. These findings show that aged rat hepatocytes have a
      higher set point for uracil nucleotides, which is consistent with the relative
      resiliency of these cells to GalN injury. Neonatal and fetal cells have the same
      set point for these nucleotides as adult rats, but are relatively resistant to
      GalN-induced depletion. In conclusion, the differences in toxicity of GalN may
      reside in age-related differences in the regulation of uracil nucleotide
      biochemistry.

PMID- 2000638
TI  - Potentiation of cocaine hepatotoxicity by ethanol in human hepatocytes.
AB  - The hepatotoxic effects of cocaine on the human liver and the effect of ethanol
      on cocaine-induced hepatotoxicity have been examined in adult human hepatocytes
      cultured in chemically defined conditions. Cultures were exposed to
      concentrations of cocaine ranging from 10(-2) to 10(-5) M. Cytotoxicity was
      evaluated after 24 hr of continuous exposure to cocaine by measuring the leakage
      of intracellular LDH and the ability of cells to reduce MTT. According to these
      end-point parameters, half-maximal cytotoxic concentrations of cocaine for human
      hepatocytes (IC50) were 6.8 and 7.8 mM, respectively. Lower concentrations of
      cocaine, however, impaired basic metabolic functions of human hepatocytes.
      Exposure of cells to 2 mM cocaine for 24 hr resulted in a 50% decrease in hepatic
      glycogen, a 40% decrease in cellular glutathione content, and a 40% decrease in
      urea synthesis with respect to control values. For most of the metabolic
      parameters assayed, significant alterations were observed at 0.5 mM cocaine.
      Glycogen reloading of hepatocytes began to be inhibited in the presence of 0.60
      mM cocaine (IC10). Ethanol greatly potentiated cocaine-induced hepatotoxicity.
      After a 48 hr pretreatment of human hepatocytes with 50 mM ethanol, low
      concentration of cocaine (0.25 mM) that had no effects on hepatocyte metabolism
      in the absence of ethanol caused a 20% inhibition of the urea synthesis rate, a
      40% degradation of glycogen stores, and a 30% reduction in glutathione content.
      The results of our work show that ethanol increases the effects of cocaine on
      human hepatocytes by a factor of 10.

PMID- 2000639
TI  - Allylamine and acrolein toxicity in perfused rat hearts.
AB  - We assessed the in vitro toxicity of the cardiovascular toxicant allylamine, and
      its presumed in vivo metabolite, acrolein. In dose-response experiments, rat
      hearts perfused with allylamine (10-30 mM) or acrolein (0.01-3.0 mM) for 2 hr
      were assessed by standard histopathology and assay of creatine kinase (CK) in
      effluent. Allylamine-perfused hearts showed no grossly apparent functional
      abnormality except at 30 mM, but acrolein-perfused hearts beat irregularly and
      stopped rapidly (within 15 min at 0.01-0.3 mM, and by 5 min at 3.0 mM). Extensive
      contraction band necrosis and an apparently dose-dependent loss of CK were
      evident in allylamine-perfused hearts, whereas acrolein perfusion resulted in no
      morphologic lesions or CK loss. Additional experiments, however, suggest that
      acrolein perfusion results in denaturation of CK, making it undetectable in
      effluent. In hemodynamic preparations of rat hearts perfused with 10 mM
      allylamine, contraction band necrosis and extensive mitochondrial changes were
      seen by electron microscopy. Allylamine caused a marked rise in left ventricular
      pressure at 5 and 10 min, followed by a slow decline to a markedly depressed
      level at the end of 2 hr. End diastolic pressure rose steadily throughout the 2
      hr perfusion. Coronary flow was similar in control and allylamine-perfused hearts
      for 1 hr, but then declined slowly. These experiments suggest that vascular spasm
      or alterations in coronary flow are not the cause of allylamine-induced
      myocardial damage. Allylamine's toxic effect on myocardium in this model may be
      mediated through its metabolism and subsequent injurious intracellular events.

PMID- 2000640
TI  - Plasma membrane-specific phospholipase A1 activation by nitrogen dioxide in
      pulmonary artery endothelial cells.
AB  - Nitrogen dioxide (NO2), an environmental oxidant, alters the plasma membrane
      structure and function of pulmonary artery endothelial cells through peroxidative
      injury. Because perioxidative injury can activate membrane phospholipases and
      alter phospholipid composition of membranes, we evaluated the effects of NO2
      exposure on phospholipase A1 (PLA1), phospholipase A2 (PLA2), and diacylglycerol
      lipase (DG lipase) activities in pulmonary artery endothelial cell plasma,
      mitochondrial, and microsomal membranes. We also evaluated the effect of NO2
      exposure on the phospholipid composition of plasma membranes of these cells.
      Exposure to 5 ppm NO2 for 48 hr resulted in a significant (p less than 0.01)
      increase in PLA1 activity in plasma membranes but not in mitochondrial or
      microsomal membranes of pulmonary artery endothelial cells, whereas PLA2 and DG
      lipase activities were comparable to controls in all membranes. As a result of
      PLA1 activation, the total phospholipid content of the plasma membranes of NO2
      exposed cells was significantly (p less than 0.01) reduced compared to controls.
      Phosphatidylethanolamine (PE) content was reduced (p less than 0.05), whereas
      lyso-PE (LPE), a product of PLA1 hydrolysis of PE, as well as phosphatidylserine
      (PS) contents were increased (p less than 0.01 for both LPE and PS) in the plasma
      membranes of NO2-exposed cells. Incorporation of exogenous PS into pulmonary
      artery endothelial cells mimicked the stimulatory effect of NO2 on PLA1 activity.
      These results demonstrate that NO2 specifically reacts with the plasma membrane
      component of pulmonary artery endothelial cells, causing specific activation of
      PLA1. The NO2-induced increase of PS in the plasma membranes appears to be
      responsible for the specific activation of PLA1 in pulmonary artery endothelial
      cells.

PMID- 2000641
TI  - Pentamidine: an inhibitor of interleukin-1 that acts via a post-translational
      event.
AB  - Pharmacologic inhibition of cytokines, particularly interleukin-1 (IL-1),
      potentially has numerous therapeutic applications in inflammatory diseases. We
      demonstrate that pentamidine, an aromatic diamidine currently used to treat
      Pneumocystis carinii pneumonia, is a specific and effective inhibitor of cellular
      IL-1 release from macrophages, and we have shown that this blockage occurs at
      neither the transcriptional nor the translational level. Pentamidine induced
      inhibition of IL-1 occurs via an alteration in the post-translational
      modification of the protein, altering the intracellular and/or membrane cleavage
      of the 31-kDa pro-IL-1 to the 17-kDa secreted form. In addition, pentamidine
      exhibited less broad immunosuppressive actions when compared to a corticosteroid,
      the classical therapeutics utilized for inhibition of cytokine production.

PMID- 2000642
TI  - Correlation of hepatocellular proliferation with hepatocarcinogenicity induced by
      the mutagenic noncarcinogen:carcinogen pair--2,6- and 2,4-diaminotoluene.
AB  - 2,4-Diaminotoluene (2,4-DAT) and 2,6-diaminotoluene (2,6-DAT) are equally
      genotoxic in the Ames/Salmonella assay and are both readily absorbed,
      metabolized, and excreted and metabolites of both compounds are mutagenic with
      metabolic activation. However, there are marked differences in the results of
      chronic rodent bioassays with these two compounds. 2,4-DAT is a potent
      hepatocarcinogen whereas 2,6-DAT failed to produce an increased incidence of
      tumors in any tissue even when administered at a dose higher than that of 2,4
      DAT. In an effort to elucidate the source of these apparently discordant results,
      the present studies were designed to determine the effects of these two chemicals
      on cell proliferation in the liver when administered at the dose levels
      comparable to those used in the original bioassays. This study utilized repeated
      oral dosing, osmotic minipumps to deliver bromodeoxyuridine (BrDU) for 8 days,
      and immunohistochemistry to quantitate BrDU incorporation into hepatic DNA, CCl4
      (0.4 ml/rat, single ip dose) or vehicle control groups were included as positive
      and negative controls, respectively. The degree of cell proliferation was
      quantified by the labeling index from at least 1000 hepatocytes. Results from the
      control studies indicate that approximately 1.1% of the hepatocytes from vehicle
      treated animals replicated during the exposure period whereas approximately 50%
      replicated in the positive controls. The carcinogen 2,4-DAT produced a dose
      dependent increase in cell proliferation of approximately 10% and 20% in livers
      of animals exposed to 12.5 and 25.0 mg/kg/day, respectively, whereas the
      noncarcinogen 2,6-DAT produced no increase in cell turnover compared to vehicle
      control following treatment with 25.0 or 50.0 mg/kg/day. These results indicate a
      positive correlation between increased cell proliferation and
      hepatocarcinogenesis induced by these two isomers of diaminetoluene.

PMID- 2000643
TI  - [Endoscopic ultrasound scanning of the upper gastrointestinal canal].
AB  - Endoscopic ultrasound scanning (EUL) of the upper gastro-intestinal canal has
      rendered apparently very meticulous assessment of pathological conditions in and
      around the oesophagus, stomach and the duodenum possible during recent years. On
      account of the close contact with the mucosa, high-frequent ultrasound transducer
      with great solubility capacity are employed. The wall of the gastrointestinal
      canal may thus be presented and subdivided into five layers. The ultrasound
      gastroscope most employed at present is lateral visualizing gastroscope with a
      mechanically rotating sector scanner mounted distal to the optic. On the basis of
      the literature, the technique of the examination and the hitherto employed
      indications for EUL are reviewed. International attention has been focussed on
      employment of EUL for preoperative subdivision of tumours in the oesophagus,
      stomach, pancreas and biliary passages into stages. Individual centres have
      reported promising results compared with existing forms of examination such as
      CT, conventional radiography, endoscopy and external ultrasound scanning. It is
      concluded that the necessary apparatus has not yet been fully developed. In
      addition, more numerous and more extensive prospective investigations are
      necessary before EUL may possibly be considered as a routine method of
      examination.

PMID- 2000644
TI  - [The significance of cytochrome P450 gene superfamily for the clinical
      pharmacokinetics of drugs].
AB  - It is presumed that there are between 20 and 200 medicamentoxidizing cytochrome
      P450 isozymes. The formation of every P450 isozyme is encoded by a separate gene
      and the P450 gene superfamily is classified into families and sub-families on the
      basis of the degree of amino acid relationship for the isozymes which are coded.
      The genetic polymorphism for 4-hydroxylation of the anti-epileptic preparation S
      mephenytoin is associated with an isozyme in the P450IIC sub-family. In Denmark,
      approximately 3% of the population are poor metabolizers (PM) of mephenytoin.
      Mephenytoin polymorphism appears to be partially responsible for N-demethylation
      of diazepam and imipramine but the clinical significance of this is still
      obscure. Recent investigations suggest that conversion of proguanil to the active
      metabolite, cycloguanil, is reduced in mephenytoin-PM. The sparteine/debrisoquine
      oxidation polymorphism is associated with P450IID6 isozyme and 7-8% of the Danish
      population are PM. The sparteine/debrisoquine polymorphism is of significance for
      elimination of more than 20 different medicaments with clinically significant
      consequences for tricyclic antidepressants, certain neuroleptic and certain
      antiarrhythmic drugs. P450IIIA4 is the third isozyme with demonstrated
      significance for elimination of clinically significant medicaments including
      cyclosporin A. No genetic polymorphism has, as yet, been demonstrated for this
      isozyme.

PMID- 2000645
TI  - [Endoscopic ultrasound scanning of the upper gastrointestinal tract. Preliminary
      results].
AB  - International interest in endoscopic ultrasonic scanning (EUL) for assessment of
      mural and extramural pathology in and around the upper gastrointestinal tract has
      increased during recent years. Since 1. February 1989, the surgical
      gastroenterological department D in cooperation with the ultrasonic laboratory in
      Gentofte Hospital has undertaken EUL on selected patients employing a recently
      developed Picker-Pentax ultrasonic gastroscope. The apparatus consists of a
      forward viewing fibreoptic gastroscope with a 5 MHz curved electronic ultrasonic
      transducer mounted immediately behind, the optic. The plans of scanning is
      longitudinal in the length of the gastroscope. On the basis of in vitro
      ultrasonic examinations and EUL in a total of 80 patients during a period of 12
      months, the preliminary experience with the above mentioned apparatus is
      described. It is concluded that the 5 MHz transducer is not sufficiently high
      frequent for detailed examination of the mucosa and the walls of the
      gastrointestinal canal whereas deep penetration and imaging of the surrounding
      organs and structures is satisfactory. The method demands great endoscopic
      routine and extensive UL experience as the UL sectional image is unpredictable
      and difficult to define, one of the reasons being that the transducer is not
      visible through the gastroscope. The indications for employing the apparatus
      described here are not completely elucidated and assessment of the diagnostic
      certainty of the method requires more numerous and controlled investigations. The
      authors consider that EUL with linear array transducer as the most recent
      invention will result in increased diagnostic information in gastroenterology.

PMID- 2000646
TI  - [Survival of patients with intracranial tumors before and after CT].
AB  - Survival was compared between 135 patients (II) with intracranial tumours (IT)
      diagnosed with the aid of CT and 170 cases of IT (I) diagnosed in the same
      department prior to the introduction of CT. Apart from fewer cases of
      oligodendrogliomata in group II, the distribution into histological types was
      identical in the two groups. The age and sex distributions were identical. The
      percentages in the groups (I/II) of operations (85.7/60.7), autopsy (41.1/15.3)
      and histological determination of the tumour (87.6/58.5) had decreased
      considerably while employment of chemotherapy had increased (1.8/20.7). On the
      whole, survival from the time of diagnosis was found to be better in group (II)
      (p = 0.026). Survival from the onset of the disease was the same (p = 0.47)
      indicating that CT had resulted in earlier diagnosis but not a generalized
      improvement in survival in the entire group of tumour patients. Significantly
      better survival was found for the histologically verified malignant tumours in
      group II both for the primary tumours (p = 0.001) and for metastases (p =
      0.0058). In this group, survival was found to be improved both from the time of
      diagnosis (p = 0.0001) and from the onset of symptoms (p = 0.015). It appears
      from the literature that there is a generalized tendency to omit histological
      verification of IT frequently in cases where CT suggests a hopeless prognosis.
      Greater advantages as regards survival with CT may probably be obtained with more
      frequent employment of stereotactic biopsy.

PMID- 2000647
TI  - [Neck lymph node metastases from an unknown primary tumor].
AB  - During a period of 12 years, a total of 203 patients with lymph node metastases
      in the neck were referred. At the conclusion of the programme of investigation,
      the primary tumours remained undiagnosed in 37 patients. The primary tumours were
      diagnosed in 18 patients, ten of these were alive. The primary tumours were most
      commonly localized in the head and neck region with the possibility for curative
      treatment. Patients with small metastases experienced good effects from regional
      treatment in the form of cervical dissection and radiotherapy with a five-year
      crude survival of 53%

PMID- 2000648
TI  - [Compression stockings contra ace-bandages in the treatment of acute ankle
      distorsions. A prospective randomized study].
AB  - Sprained ankles are most often treated with ace-bandages. The aim of this study
      was to investigate the effect of compressing antiembolism stocking (T.E.D.)
      versus the ace-bandage in a prospective randomised trial. Evaluation was based on
      the duration of pain, swelling, limp and absence from daily routines (job, daily
      activity and sport). The study included 149 patients. We found no difference
      between the two treatments, on the basis of 95% confidence interval at the
      difference between the treatments. On the basis of this trial we cannot recommend
      one treatment rather than the other, but it must be borne in mind that the ace
      bandage is cheaper.

PMID- 2000649
TI  - [Communal housing for the mentally ill. A supplement or an alternative to the
      existing psychiatric institutions].
AB  - In 1980-1981, two communal housing schemes for young psychiatric patients in the
      Municipality of Copenhagen were established. The object was to offer these
      persons a home for a limited period (maximum three years). The object of this
      investigation is to describe the patients who lived in these communal homes
      during the period 1.3.1980-28.2.1989, to investigate the duration of
      hospitalization in psychiatric departments two years before and two years after
      they stay in the communal home and, on the basis of the experience gained, to
      discuss the possibilities and limitations of this form of housing. The
      investigation is retrospective and based on hospital case records. It includes 56
      persons: 37 men and 19 women. The average age was 28.7 years. 92% of the
      residents had a chronic psychiatric disease. They had received psychiatric
      treatment early and had long histories with prolonged periods of hospitalization.
      The average duration of hospitalization was 17 months. At the conclusion of the
      investigation, 33 residents had moved out two or more years ago. The average
      duration of hospitalization for this group was reduced to approximately 1/3 of
      the duration of hospitalization prior to the stay in the communal home. The
      structure outlined here may be employed for a number of the chronic psychiatric
      patients but a communal psychiatric offer should include a greater spectrum of
      possibilities for chronic patients to cover their requirements. Establishing an
      offer of this type demands multidisciplinary cooperation.

PMID- 2000650
TI  - [Planning of prenatal care in hospital districts in 1988/1989].
AB  - In this investigation, the planning of antenatal care in the Danish hospital
      districts was compared with the directives for antenatal and maternity care
      issued by the Danish Ministry of Health in 1985. Information about planning was
      obtained by means of a questionnaire sent to the authorities responsible. The
      results reveal that, in the hospital districts, there is a tendency to emphasize
      routine measures at the expense of services based more on requirements. In
      addition, the investigation reveals that planning differs in the various hospital
      districts, and that in many hospital districts, local conditions in maternity
      clinics and midwives' centres may be decisive for planning. The health services
      which are offered to pregnant women with the same requirements are thus
      characterized by geographic variations. Finally, the investigation reveals that
      the hospital districts deviate from the directives issued by the Ministry of
      Health in their planning of antenatal care. The possible reasons for this are
      discussed.

PMID- 2000651
TI  - [Future prospects of the specialty of infectious diseases].
AB  - Infectious diseases were established as a subspecialty of internal medicine in
      Denmark in 1982. Ten permanent senior positions in Danish hospitals are at
      present held by specialists in infectious diseases. Simultaneously, seven
      specialists in infectious diseases employed in junior positions are qualified for
      senior positions. This number will increase to 15 by 1995. It is concluded that:
      1. There is a serious imbalance in the specialty of infectious diseases between
      the number of senior positions available and the number of qualified specialists.
      2. The reluctance on the part of hospital administrators to create new positions
      in the specialty of infectious diseases cannot be based on the fear of the lack
      of qualified applicants.

PMID- 2000652
TI  - [Elephantiasis nostras. A rare complication to erysipelas].
AB  - A case of elephantiasis nostras in a lower limb is presented. A thorough
      programme of investigation could only reveal a single episode of erysipelas as
      the possible etiological origin. The therapeutic possibilities are briefly
      reviewed. The most important are early institution of adequate antibiotic
      treatment and antibiotic treatment of every recurrence of disease.

PMID- 2000653
TI  - [Epidurography in insufficient epidural analgesia].

PMID- 2000654
TI  - [Severe hypoglycemia and clouding of consciousness caused by deficiency of the
      connecting link acyl CoA dehydrogenase].
AB  - A case of severe hypoglycaemia precipitated by fasting in a child is described.
      As a result of the hypoglycaemia, the patient became brain damaged. The mechanism
      causing the hypoglycaemia was a defect in the fatty acid beta-oxidation enzyme,
      the connecting link acyl-CoA dehydrogenase. During a prolonged fast, fatty acids
      are not converted to acetyl-CoA and ketone bodies which participate in Kreb's
      cycle for production of energy to a sufficient extent. This result in non-ketotic
      hypoglycaemia with excretion of organic acids in the urine. As a rule, the
      symptoms occur for the first time during the first to second years of life in
      connection with common infectious diseases, with vomiting followed by clouding of
      consciousness and possibly coma, but the condition may also present with sudden
      unexpected death. Treatment consists of intravenous glucose. The diagnosis is
      established by testing the urine for hexanoylglycin and other substances and is
      confirmed by culture of skin fibroblasts and measurement of beta-oxidation
      activity. The disease is an autosomally recessive inherited condition. In
      families where there have been cases of unexplained hypoglycaemia and clouding of
      consciousness and cases of unexplained death in infancy or "near misses", all of
      the family members should be offered examination for the above mentioned enzyme
      deficiency.

PMID- 2000655
TI  - [Severe nortriptyline poisoning in poor metabolizers of the sparteine type].
AB  - Approximately 7% of the Danish population are so called poor metabolizers (PM) as
      regards the model compound sparteine. These individuals lack the P450 isozyme
      which is mainly responsible for elimination of at least 20 different medicaments
      including nortriptyline. A woman aged 42 years suffering from depression was
      treated with 100 mg nortriptyline daily and, during the course of treatment, she
      developed a toxic serum nortriptyline level (approximately 2,100 nM). Treatment
      was withdrawn temporarily on account of severe side-effects. The depression
      recurred. During the medicine-free period, a sparteine test was performed and
      this demonstrated that the patient was a poor metabolizer. Scarcely two months
      after hospitalization, treatment was recommenced with 25 mg nortriptyline daily
      after which the patient's depression disappeared completely without any side
      effects of note.

PMID- 2000656
TI  - [Poisoning with the brown roll-rim mushroom, Paxillus involutus].
AB  - Brown Roll-Rim (Paxillus involutus) is a dangerous poisonous mushroom with
      symptoms of poisoning which occur a few hours after consumption. Repeated
      consumption may cause sensitization to a heat-stable toxin, resulting in
      haemolysis which may be of all degrees. In addition, severe gastrointestinal
      symptoms may be due to a heat-instable toxin. In cases with immune haemolysis,
      treatment consists of corticosteroid and possibly plasmapheresis and symptomatic
      therapy.

PMID- 2000657
TI  - [Physicians' activities on inspection ships in the North Atlantic].

PMID- 2000658
TI  - [Moclobemide (Aurorix). A new monoamine oxidase inhibitor not requiring dietary
      restrictions].

PMID- 2000659
TI  - [Significant extrapulmonary manifestations of sarcoidosis].
AB  - Sarcoidosis is a granulomatous multisystem disorder of unknown genesis. Although
      the course is most often benign and self-limiting, serious or life-threatening
      extrapulmonary manifestations may occur when heart, central nervous system,
      kidney or the haemopoietic system are involved. In these cases, corticosteroid
      treatment is necessary to suppress the inflammation, prevent fibrosis in vital
      organs, and improve the general condition.

PMID- 2000660
TI  - [Cerebral symptoms in 3,387 men and occupational exposure to organic solvents. An
      epidemiological study].
AB  - In The Copenhagen Male Study, an epidemiological study comprising 3,387 men aged
      53 to 75 years, 3,303 men with valid questionnaire answers to questions on
      occupational organic solvents exposure, four cerebral symptoms and current work
      status were examined. Two hundred and ninety-five men had been occupationally
      exposed to mixed organic solvents for a period of five years or more. Among the
      exposed persons, 178 had retired, while 117 were still gainfully employed. The
      exposed men in both groups had highly significantly more complaints of decreased
      concentration and defective memory. Among the exposed retired men a higher
      prevalence of headache was found. Among the exposed men who were still employed a
      trend towards a higher prevalence of vertigo was found. This study was conducted
      within a cardiovascular study with no focus on the relationship between organic
      solvent exposure and cerebral symptoms, a design reducing the risk of
      overreporting. If overreporting was responsible for the differences found between
      solvent exposed and unexposed a similar pattern for reporting of acute and
      chronic symptoms should be expected. This was not the case. Our results support
      the hypothesis, that occupational exposure to organic solvents for a period of
      five years or more increases the risk of developing persistent defective memory
      and decrease in concentration.

PMID- 2000661
TI  - [Deaths due to poisoning in Denmark in 1983-1987].
AB  - Deaths due to poisoning in Denmark during the five-year period 1983-1987 are
      described on the basis of the information from the register of causes of deaths
      in the Danish Institute of Clinical Epidemiology. The average annual number of
      deaths due to poisoning was 935.63% of these were suicides, 21% accidents, less
      than 1% manslaughter and in 16% of the cases the manner of death had not been
      established. 68% were due to medicaments, nearly half of these unspecified, 25%
      were due to carbon monoxide, 5% to alcohol, and 2% to other causes. The value of
      this account is restricted by the fact that not all of these deaths were
      submitted to medico-legal investigation, and that there were technical
      limitations in the classification and coding of causes and manners of death. In
      this connection, it is emphasized that almost one third of the deaths due to
      poisoning were caused by an unknown medicament. Differences in manners and causes
      of death are noted by comparing the results of this account to the material from
      the institutes of forensic medicine concerning chemically investigated deaths due
      to poisoning. This account applies to the prophylaxis of deaths due to poisoning,
      with special reference to medical drugs in general, carbon monoxide, alcohol,
      alcohol in combination with medicaments or narcotics, and over-the-counter
      analgesics containing acetylsalicylic acid. It is concluded that a more carefully
      examined representative material is required.

PMID- 2000662
TI  - [Triazolam (Halcion) poisoning].
AB  - Benzodiazepines have been regarded as relatively "safe" drugs where fatal
      poisonings are concerned. The very potent benzodiazepines have, to a certain
      extent, changed this viewpoint and since triazolam was introduced in Denmark in
      1978, six fatal intoxications have occurred in East Denmark. Triazolam analyses
      were performed by capillary gas chromatography with an electron capture detector.
      In the only case where no ethanol was present, a blood triazolam concentration of
      0.3 mumol/kg was detected. In one case no blood was available because of
      putrefaction, and muscle was analysed for triazolam instead of blood. The
      concentration range in the four cases with an ethanol concentration of 1-2 mg/g
      is 0.1-0.6 mumol/kg. The blood concentrations from these six fatal intoxications
      are compared to blood concentrations from living persons. The whole blood
      concentrations from living persons were in the range 0.005-0.08 mumol/kg (n = 28)
      with an average concentration of 0.034 mumol/kg.

PMID- 2000663
TI  - [Colonoscopy after radical surgery for colorectal cancer. A 10-year prospective
      study of 309 patients].
AB  - Experience from ten year colonoscopic follow-up in patients after radical surgery
      for colorectal cancer is presented. In all, 309 patients below 76 years were
      included from 1978 to 1983. All had preoperative proctoscopy and barium enema.
      Colonoscopy was performed perioperatively, every six months the first three
      years, four and five years, seven to eight years and ten years after surgery. A
      minority had double-contrast barium enemas. Synchronous adenomas were removed
      during surgery and at perioperative colonoscopy and these patients had the same
      risk of metachronous cancer as those without synchronous adenomas. Five patients
      with six metachronous cancers, all had new curative surgery. Patients with
      synchronous adenomas had a higher risk of metachronous adenomas, but had a better
      prognosis than those without synchronous adenomas. Colonoscopically demonstrated
      intraluminal local recurrence in the colon could not be treated with new radical
      surgery in contrast to four out of eight intraluminal recurrences in the rectum.
      Most local recurrences were extraluminal and were diagnosed by other means.

PMID- 2000664
TI  - [Metachronous colorectal cancer].
AB  - The occurrence of metachronous colo-rectal cancer was investigated in 903
      patients under the age of 40 years at the time of diagnosis of the primary
      cancer. A constant frequency of metachronous colo-rectal cancers was found and a
      cumulated incidence of 30% after an observation period of 41 years. Metachronous
      cancer of the colon was encountered most frequently in the right half of the
      colon regardless of the site of the primary cancer. On the basis of the above
      mentioned results, a life-long follow-up programme is recommended, consisting of
      regular examination for blood in the faeces and colonoscopy.

PMID- 2000665
TI  - [Purulent meningitis in childhood. Treatment results in 87 children between 7
      month and 15 years of age].
AB  - The children were admitted over a 14-year period (1975-1988) from an admission
      area of average Danish population distribution. The incidence was 15.5/100,000
      children per year. The area had endemics of meningococcal disease in the years
      1983-1984. The etiology was meningococcal in 43%, Hemophilus influenzae in 33%
      and pneumococci in 9% of the patients. Regardless of etiology, the antibiotic
      schedule was ampicillin 400 mg/kg body weight/day. Resistance to ampicillin was
      not found in any of the bacterial cultures. Within two weeks before admission 59%
      of the children had experienced a febrile illness. The diagnosis of meningitis
      was missed before admission in 24% of the cases. On admission, 93% had typical
      clinical signs of meningitis. 87% were lethargic or comatose. 31% had convulsion
      and in 13% the peripheral circulation was compromised. Recrudescence was
      suspected in one patient. Sequelae were most commonly found in children with
      meningococcal meningitis and were persistent in 23% of all the children. Severe
      or less severe neurological handicaps were seen in 29% (psychomotor retardation,
      epilepsy, cerebral palsy and hearing loss). One patient with Waterhouse
      Friederichsens syndrome died. Thus the overall mortality was 1.2%, which is low
      compared to treatment results reported by others.

PMID- 2000666
TI  - [Fever during treatment for bacterial meningitis in children].
AB  - Eighty-seven infants and children aged 1 month to 15 years admitted to the
      Pediatric Department, Randers Central Hospital 1975-1988 with bacterial
      meningitis were evaluated with special interest in the course of fever and its
      relation to sequelae. The children were treated with ampicillin (400 mg/kg/day).
      We found that 94% were afebrile after six days. 10% had persisting fever, 1%
      prolonged fever and 38% were found to develop secondary fever. Significantly more
      children infected with H. Influenzae had secondary fever. In most cases, no
      reason for secondary fever was found (46%). 18% had drug fever and only one case
      of relapse was found. 23% had severe sequelae. No significant relationships
      between persistent, prolonged or secondary fever and sequelae were found.

PMID- 2000667
TI  - [Course of delivery in obese women after normal pregnancies].
AB  - The course of deliveries in 134 obese women in whom the pregnancies had been
      normal were compared with a matched control group of women with normal weights.
      More of the obese women had second stages of labour lasting for more than one
      hour. Apart from this no differences were observed in the frequencies of
      complications, the nature of the complications or the number of interventions
      during delivery. The frequencies of infants weighing more than 4,000 g were
      identical in both groups but were high compared with other investigations. In the
      group of obese mothers, significantly more infants were found to have Apgar
      scores of 7 or less after one minute. An association was found between a long
      second stage and low Apgar score in five out of 12 infants in the obese group.
      Two out of three infants with shoulder dystocia, all born to obese mothers, had
      low Apgar scores. It is emphasized that in obese parturient women, particular
      care should be employed to ensure optimal conditions in the active phase and
      during the actual delivery. Stimulation with syntocin and episiotomy are
      recommended on liberal indications. Apart from this, there does not appear to be
      any need for increased observation of obese parturient women, provided that
      pregnancy has been normal.

PMID- 2000668
TI  - [The national patient register--a research tool?].
AB  - In connection with an analysis of rupture of the uterus in Denmark during the
      period 1980-1987, the authors found that 956 patients were registered as having
      rupture of the uterus in the Danish national patient register. Review of the
      individual cases revealed that the correct number was only 129, i.e. that only
      14.1% were correctly registered. The authors consider it unsatisfactory that such
      an extensive register of this type cannot be employed without controlling the
      records of each individual patient.

PMID- 2000669
TI  - [Diagnosis of popliteal cysts and their complications].
AB  - Popliteal cysts and their complications (rupture, expansion and pseudothrombosis)
      all of which may simulate deep venous thrombosis of the lower extremity may be
      diagnosed reliably by ultrasonography. Even small cysts can be detected, their
      extension can be defined and rupture with leakage of fluid into the surrounding
      muscles can be diagnosed. Phlebography can be avoided in most cases. Arthrography
      rarely gives additional information. Ultrasonography of the erect patient is
      recommended if rupture is suspected.

PMID- 2000670
TI  - [Placing of implantable devices for electric stimulation].
AB  - Various electrical devices are implanted for cardiac-, diaphragma-, pain- and
      musclestimulation. The stimulator/pacemaker can be implanted in locations,
      different from that of ordinary cardiac pacemakers. All electric stimulation
      equipment containing batteries must be removed before cremation on account of the
      risk of explosion.

PMID- 2000671
TI  - [Pulmonary sarcoidosis or intrathoracic malignant lymphoma--the significance of a
      histological diagnosis].
AB  - The clinical appearance of sarcoidosis and the changes seen on x-ray of the
      thorax are often typical. However, several other conditions may present the same
      symptoms and identical x-ray findings. The present case report emphasizes the
      importance of an invasive approach and of histological investigation in patients
      in whom carcoidosis is suspected. For almost one year, a man aged 29 years was
      considered to be suffering from sarcoidosis on account of the clinical symptoms
      and bilateral hilar adenitis on x-ray op the thorax. He was treated with steroid
      for several months with clinical and radiological response. After the illness has
      lasted for one year, bronchoscopy was performed and bronchial biopsies revealed
      the diagnosis of malignant lymphoma.

PMID- 2000672
TI  - Radical prostatectomy after definitive radiation therapy for prostate cancer.
AB  - Radical prostatectomy was performed in 14 patients following local failure of
      radiation therapy for adenocarcinoma of the prostate. Ten patients were treated
      with external beam and 4 with interstitial radiation. The interval from beginning
      radiation therapy to biopsy-proved residual or recurrent disease was twenty-four
      to one hundred fourteen months (mean 61 months). Ten patients had significant
      anterior and lateral fibrosis. Five patients had loss of tissue planes between
      the prostate and rectum, however, no rectal injuries occurred. Estimated blood
      loss was 300-8,000 cc (median 1,000 cc). Operative time was one hundred ten to
      three hundred seventy-five minutes (median 185 minutes). Significant late
      complications are impotence (100%) and incontinence (55%). Tumor volume was 1.1
      27.2 cc (mean 11.1 cc). Seven patients had seminal vesicle involvement, 9 had
      level III capsule penetration, and 6 had positive surgical margins. Follow-up
      ranges from one to fifty-two months (median 18 months). Currently, 6 patients are
      clinically without disease and have serum prostate-specific antigen (PSA) of 0.0
      ng/mL. Four patients have no clinical evidence of disease but do have detectable
      serum PSA, and 4 patients have evidence of metastatic bone disease on bone scan
      with elevated serum PSA levels. Radical prostatectomy following radiation therapy
      has no greater immediate morbidity or mortality compared with radical
      prostatectomy without prior irradiation and takes only slightly longer to
      perform. However, there is a marked increased risk of impotence and incontinence.
      More patients followed for a longer time are needed to assess the benefit of
      radical prostatectomy on survival of patients who fail radiation therapy.

PMID- 2000673
TI  - Gleason's histologic grading as clinical prognostic marker in patients with
      advanced prostatic carcinoma.
AB  - We have found that the Gleason's histologic grading system is a good clinical
      marker to predict long-term response and prognosis in symptomatic Stage D-2
      adenocarcinoma of the prostate. In this retrospective study, 56 cases were
      reviewed and correlated with bone scan, acid phosphatase, and symptomatology
      following bilateral orchiectomy.

PMID- 2000674
TI  - Simultaneous presentation of adenocarcinoma of prostate and transitional cell
      carcinoma of bladder.
AB  - Simultaneous presentation of transitional cell carcinoma of the bladder and
      adenocarcinoma of the prostate is not uncommon. Twenty-two patients were
      diagnosed as having simultaneous or concurrent presentation of prostate and
      bladder carcinomas between January 1970 and July 1986. The overall five-year
      survival was 40 percent, with patients presenting with prostate cancer doing
      better (50%) than those with bladder cancer (32%). Retrospective review of these
      cases suggests that primary therapy should be directed to the most advanced
      cancer. Incidental prostate cancer may be "cured" with a cystoprostatectomy and,
      when indicated, radiation therapy added postoperatively for the bladder cancer.
      Eleven patients presented with Stage A prostate cancer: 10 of the 11 were treated
      for their bladder cancer. Treatment was usually radical cystoprostatectomy with
      or without postoperative radiation. None died of prostate cancer. Patients
      presenting with advanced stage prostate cancer have had recurrence or have died
      of the cancer.

PMID- 2000675
TI  - Interstitial cystitis: successful management by increasing urinary voiding
      intervals.
AB  - A variant of the interstitial cystitis (IC) syndrome, minimal or no pain or
      significant pain that has been lessened by another therapy, can be clinically
      improved by retraining of the individual's voiding pattern. Patients with greater
      pain but capable of completing this protocol also may be helped. While this group
      of patients fills the diagnostic criteria of IC and has many of the classic
      changes, many differ in that they have minimal or no pain, while simultaneously
      they have a dysfunctional bladder as expected from long-term low-volume voiding.
      All patients were placed on a protocol which focused on progressively increasing
      intervals between voids. Fifteen to thirty minutes initially were added to their
      present voiding time. The same increase was added to the voiding pattern every
      three or four weeks until an interval of three to four hours between voids was
      achieved. Twenty-one patients fit the criteria to be entered into this study.
      Overall 71 percent (15/21) had successful management of their symptoms and
      reported a 50 percent decrease in their symptoms of urinary urgency, frequency,
      and nocturia. Nineteen percent (4/21) reported 25 percent decrease in symptoms
      and 10 percent had no change. Presence of significant pain adversely affects
      outcome, 3/7 (with pain) improvements versus 12/14 (without pain). For all
      patients there was a significant increase in bladder capacity (92 mL average
      before study and 179 mL after) and average daily voids (13.2/day prestudy and 7.4
      post-therapy). These differences in voided profiles were statistically
      significant (p value less than 0.01).

PMID- 2000676
TI  - Symptom analysis of patients undergoing modified Pereyra bladder neck suspension
      for stress urinary incontinence. Pre- and postoperative findings.
AB  - The results of a physician-directed follow-up of 145 women undergoing the
      modified Pereyra bladder neck suspension from March 1980 to February 1986 are
      presented. Median follow-up was 3.5 years (2.0-7.7); 70 percent of patients had
      follow-up between three and four years postoperatively. All patients had
      preoperative demonstration of stress incontinence as well as urodynamic
      evaluation. Fifty-one percent of patients reported no stress incontinence and 76
      percent reported that their sense of urinary control was better, or much better
      at the time of follow-up. Improvement was seen in all grades of stress
      incontinence. Age, weight, parity, and history of prior anti-incontinence surgery
      had no significant impact on success rates. Although preoperative urgency
      symptoms were more common among failure (28% vs 15%), this association was not
      statistically significant. However, persistent or de novo urgency symptoms
      postoperatively were highly associated with postoperative incontinence (p less
      than 0.005). The onset of recurrent incontinence was experienced more than two
      years postoperatively in 23 percent of the incontinent group.

PMID- 2000677
TI  - Incontinence management scale for elderly inpatient men.
AB  - For many elderly inpatients, urinary incontinence cannot be successfully treated
      and the management objective is identifying a suitable method for containment of
      urine loss. In elderly inpatient men, an external catheter is utilized in many
      cases for incontinence management. The role of the severity of incontinence and
      the use of an external catheter was investigated in 66 elderly inpatient men.
      Quantitative incontinence measurements showed incontinent patients having an
      external catheter had approximately 6.3 (SD = 2.5) episodes per day compared with
      3.2 (SD = 2.0) episodes per day in the noncatheter incontinent patients. The
      clinical management method used in these patients was associated with the
      measured severity of incontinence.

PMID- 2000678
TI  - Hypogonadal impotence treated by transdermal testosterone.
AB  - The transdermal therapeutic system for testosterone (TTS-T) (ALZA Corp.), applied
      to the scrotal skin for twenty-two hours daily, was tested for twelve weeks on 4
      men with hypogonadal impotence; 2 of these men wore TTS-T for as long as twenty
      six months. The 40 cm2 system delivered a daily dose of 2.8 +/- 0.16 (S.E.) mg
      (nominal dose 2.4 mg) and the 60 cm2 system delivered a dose of 3.99 +/- 0.24 mg
      (nominal dose 3.6 mg). Both systems promptly increased serum testosterone and
      dihydrotestosterone (DHT) to physiologic levels, restoring normal erectile
      activity with an increased frequency of ejaculation and a positive effect on both
      mood and energy. There were no changes in serum sex binding globulin and
      estradiol, prostate or breast size, hematologic or liver function measures, or
      urinary flow and frequency. There were no significant changes in serum
      cholesterol or low-density lipoproteins, but high-density lipoproteins tended to
      decline slightly. There were no dermatologic problems associated with the system.
      The tenfold increase in DHT over baseline levels was attributed to 5-alpha
      reduction of testosterone in the scrotal skin. The TTS-T is convenient, reliable,
      and mimics normal physiologic testosterone secretion and levels more closely than
      conventional methods of testosterone replacement.

PMID- 2000679
TI  - Bilateral emphysematous pyelonephritis.
AB  - Emphysematous pyelonephritis is an uncommon and serious infection associated with
      gas-forming coliform bacteria. Bilateral involvement is rare with only 10
      reported cases in the English literature. Prompt and aggressive management is
      required to salvage these patients. Preservation of renal function using broad
      spectrum antibiotics and surgical drainage provide the greatest benefit to these
      patients. Three new cases are presented with a brief review of the results of
      management in the reported cases.

PMID- 2000680
TI  - Results of surgical treatment of kidney cancer with solitary metastasis to
      contralateral adrenal.
AB  - A large series of patients were reviewed in two major teaching institutions, and
      patients with a carcinoma of the kidney with a solitary metastatic deposit in the
      contralateral adrenal were identified. Their survival was analyzed and compared
      with the survival of those patients having a solitary metastatic deposit in other
      organs.

PMID- 2000681
TI  - Predisposing factors in bladder calculi. Review of 100 cases.
AB  - One hundred patients, aged twenty to ninety-two years, underwent 111 procedures
      for removal of bladder calculi. Most patients (88) had some type of bladder
      outlet obstruction. Two types of stones were identified: those that had
      apparently formed in the upper tract and been trapped in the bladder (17 cases)
      and those that appeared to have formed in the bladder in the presence of various
      types of outlet obstruction. Stone analysis revealed uric acid stones in 50
      percent, calcium oxalate stones in 19 percent, and stones of mixed composition in
      31 percent. Five patients had metabolic abnormalities predisposing to stone
      formation; in 2 cases, these abnormalities were discovered during the evaluation
      for stone disease. Treatment depended on stone characteristics, associated
      pathology, and the general health of the patient. A review of the literature with
      regard to the morbidity and mortality of combining treatment of vesical calculi
      and bladder outlet obstruction secondary to prostatic obstruction is included.

PMID- 2000682
TI  - Endoscopic treatment of vesicoureteral reflux in children with neurogenic
      bladders.
AB  - Endoscopic subureteral injection of Teflon was performed in 12 children (20
      ureters) with neurogenic bladders and vesicoureteral reflux (grades III-IV).
      Follow-up evaluation by ultrasonography and voiding cystourethrogram at three
      month intervals up to two years revealed successful correction of the reflux in
      70 percent of the ureters.

PMID- 2000683
TI  - A dressing technique that facilitates outpatient hypospadias surgery.

PMID- 2000684
TI  - Conservative treatment in severe renal trauma.

PMID- 2000685
TI  - Pediatric testicular tumors: the Johns Hopkins experience.
AB  - Testicular neoplasms constitute 1 percent of all childhood malignancies and rank
      eighth in childhood cancer mortality. From 1970 to 1988, 25 testicular tumors in
      children eighteen years and under were seen. The majority of the patients were
      white (88%). Pathologic analysis of the tumors revealed that 68 percent were
      germinal and 32 percent were nongerminal. Staging was undertaken in all patients
      with serum markers, chest x-ray film, and computerized tomography scans or
      lymphangiography. All patients underwent radical orchiectomy, and further therapy
      was given dependent on tumor type and stage. The survival among this cohort was
      excellent, with only 3 patients succumbing to their disease. Detailed results of
      treatment, and approaches to avoid excess treatment morbidity are reviewed.

PMID- 2000686
TI  - Renal cell metastases versus liver hemangioma.
AB  - We present the case of a man with presumed metastatic renal cell carcinoma based
      on radiologic examination and weight loss, who refused treatment of any kind for
      one year. A surgical exploration to control hematuria revealed a Stage I tumor.

PMID- 2000687
TI  - Squamous cell carcinoma of prostate.
AB  - A primary squamous cell carcinoma occurring in the prostate of a sixty-nine-year
      old man is described. A radical excision that included cystoprostatectomy, total
      penectomy, scrotectomy, pubic symphysiectomy, and abdominoperineal resection of
      rectum was done. The patient died of systemic metastases six months after
      diagnosis. Review of the literature suggests that such a cancer of the prostate
      is rare, highly aggressive, and responds poorly to any mode of therapy.
      Histogenesis of this tumor remains controversial; however, it probably does not
      originate from the prostatic acinar cells.

PMID- 2000688
TI  - Causes of post-prostatectomy retention.
AB  - Forty-eight patients in urinary retention following prostatectomy underwent
      urodynamic evaluation. Fifteen patients (31%) were found to have persistent
      residual obstruction, while 14 patients (29%) had detrusor hyporeflexia. In 9
      patients (19%) a combination of outflow obstruction and detrusor hyporeflexia was
      demonstrated. In 6 patients (13%), urinary retention was due to compromised
      mental status. No abnormality was detected in remaining 4 patients (8%) on
      urodynamic evaluation. For proper evaluation of unsatisfactory voiding after
      prostatectomy cystoscopy is of limited value while urodynamic testing is
      essential.

PMID- 2000689
TI  - Abdominoplasty combined with lower urinary tract surgery.

PMID- 2000690
TI  - Closed drainage system for infant feeding tubes used as ureteral stents.

PMID- 2000691
TI  - Giant sclerosing leiomyoma of bladder presenting as chronic renal failure.
AB  - The clinical and pathologic features of a case of giant sclerosing leiomyoma of
      the bladder in a male Polynesian patient are reported. The presenting
      complication of chronic renal failure due to tumor envelopment of both ureters
      and consequent bilateral renal obstruction appears to be unique in the
      literature.

PMID- 2000692
TI  - Ureteral stump carcinoma incidentally found at cystectomy for bladder cancer.
AB  - We report on a sixty-five-year-old man with hematuria secondary to superficial
      bladder cancer. Because of previous urethral trauma, a complete transurethral
      resection of his bladder tumor could not be done. He, therefore, underwent
      cystectomy, at which time we incidentally found a transitional cell carcinoma of
      the left ureteral stump that had been left from a previous left nephrectomy for a
      World War II-related injury. This case underscores the importance of a thorough
      investigation of the complete urinary tract in a patient with hematuria or other
      urinary tract symptoms even if an obvious cause is found for his symptoms.

PMID- 2000693
TI  - Percutaneous transperineal prostate cryosurgery using transrectal ultrasound
      guidance: animal model.
AB  - Cryosurgery has previously been used successfully to treat prostatic carcinoma.
      Inability to monitor the freezing led to local complications that limited the use
      of this modality. Recent studies have shown that monitoring of the freezing
      process can be accomplished using real-time ultrasound. In this study,
      transrectal ultrasound guidance was used to guide a cryoprobe percutaneously,
      using a transperineal approach, into the prostate. The extent of freezing was
      then monitored using ultrasound, taking care not to freeze the urethra or the
      rectum. Six dogs had the procedure without any complications. This study
      demonstrates the feasibility of a noninvasive treatment for prostatic carcinoma.

PMID- 2000694
TI  - Application of microwave tissue coagulation in partial nephrectomy.
AB  - Microwave tissue coagulation was used during partial nephrectomy in 10 mongrel
      dogs, without clamping the renal artery. There were no major complications, such
      as retroperitoneal hematoma, abscess formation, or macroscopic infarction of the
      kidney tissue related to this new procedure. The advantages of microwave
      coagulation are reduced blood loss, shorter operative time, and minimal risk of
      vascular injury.

PMID- 2000695
TI  - Enzymatic deglycosylation of porcine thyroid peroxidase: effects on catalytic
      activity and immunoreactivity.
AB  - Thyroid peroxidase is a heme-containing, membrane-bound, glycoprotein enzyme that
      catalyzes iodination and coupling in the thyroid gland. It is also the antigen
      for microsomal autoantibodies that are commonly found in the serum of patients
      with autoimmune thyroid disease. We examined the effect of deglycosylation on the
      catalytic functions and the immunoreactivity of this enzyme. A highly purified,
      solubilized, large tryptic fragment of porcine thyroid peroxidase, retaining all
      of the N-linked glycosylation sites of the native enzyme and displaying full
      catalytic activity was used. It was deglycosylated by treatment with N-glycanase
      under nondenaturing conditions. The loss in relative molecular mass after
      treatment, determined by gel electrophoresis, was about 75% of the estimated
      molecular weight of the glycan portion of porcine thyroid peroxidase. Lectin
      blots performed with horseradish peroxidase-conjugated concanavalin A showed a
      similar loss in relative molecular mass but some residual carbohydrate. The
      intensity of the carbohydrate stain was consistent with the loss of about 75% of
      the glycans. Despite this loss, three different assays for catalytic activity of
      porcine thyroid peroxidase were not significantly decreased. Immunoreactivity
      measured by immunoblotting and by enzyme-linked immunosorbent assay was also
      unimpaired. These findings suggest that N-glycanase-sensitive glycans in porcine
      thyroid peroxidase do not act as antigenic determinants and play a minor role, if
      any, in catalytic activity and, presumably therefore, in the maintenance of
      protein conformation.

PMID- 2000696
TI  - Anti-triiodothyronine autoantibodies in a euthyroid woman: confirmation of
      immunoglobulin G antibodies employing protein A column chromatography.
AB  - The presence of thyroid hormone autoantibodies was investigated in a 48-year-old
      non-goitrous woman with high levels of serum total T3 and free T3. Her other
      thyroid function tests were normal. The presence of thyroid hormone
      autoantibodies were assessed in serum, acid-charcoal treated serum, IgG fractions
      and in a purified IgG fraction. the IgG fraction was separated from serum by a
      protein A-Sepharose CL-4B column chromatography and purified by gel filtration
      chromatography using Sephacryl S 200. Sera from normal individuals were used as
      controls. The results showed that the increased serum total and free T3 levels
      were caused by the presence of anti-T3 IgG autoantibodies. The results also
      indicate that protein A column chromatography is useful as a screening method for
      gross qualitative analyses of thyroid hormone autoantibodies.

PMID- 2000697
TI  - Thyroid volume and goitre prevalence in the elderly as determined by ultrasound
      and their relationships to laboratory indices.
AB  - In 569 unselected elderly subjects over 60 years from the general population of
      an iodine-deficient area, a palpation and an ultrasound investigation of the
      thyroid were performed. Additionally, thyroid hormone values were determined in
      466 of the 569 subjects (81.9%) and urinary iodine excretion in 491 subjects
      (86.3%). By palpation, no thyroid enlargement was noticed in 302 subjects
      (54.2%), goitre Ia in 98 (17.6%), goitre Ib in 94 (16.9%), goitre II in 53
      (9.5%), and goitre III in 10 (1.8%). The thyroid volumes (medians) by ultrasound
      were 18.6 ml in the entire group, in women (N = 489) 19.2 ml, and in men (N = 80)
      16.6 ml. One hundred and one subjects had a thyroid nodule (17.6%), 43 persons
      cystic lesions (7.6%). If, according to the literature, a goitre is defined as a
      thyroid enlargement of more than 18 ml in women and more than 25 ml in males, a
      goitre prevalence of 54.2% in females and of 22.5% in males was obtained. The
      goitre prevalence in the entire group was calculated as 49.7%. Thyroid hormone
      measurements showed in subjects with goitre a significant lower TSH value (p less
      than 0.001) and a higher thyroglobulin value (p less than 0.001). In summary, the
      study shows a high prevalence of goitre in elderly subjects, a high prevalence of
      nodules in these thyroids, a negative correlation of goitre volume with TSH, and
      a positive correlation of goitre volume with the thyroglobulin concentration.

PMID- 2000698
TI  - The effect of sex hormones on bone resorption by rat osteoclasts.
AB  - Although sex hormones are important in the attainment and maintenance of bone
      mass, the mechanism by which they exert their effect is unknown. We therefore
      tested the effects of estradiol-17 beta, dihydrotestosterone, and progesterone on
      osteoclasts, the cells that resorb bone. Osteoclasts were disaggregated from
      neonatal rat long bones, and incubated with or without the addition of
      osteoblastic cells or osteoblast-like cell lines. Bone resorption was assessed by
      scanning electron microscopy as the extent of excavation of the bone surface
      after incubation. We found dihydrotestosterone (1-100 nmol/l) and progesterone
      (10-1000 nmol/l) to have no significant effect on bone resorption. By contrast,
      E2 (1 nmol/l) reduced bone resorption in osteoclast cultures to which osteoblasts
      had been added, by approximately 25%, although consistent inhibition with other
      concentrations (0.01, 0.1, 10 nmol/l) was not observed. To our surprise, E2 was
      also associated with a delayed, dose-responsive, stimulation of bone resorption,
      in the range 0.1-10 nmol/l, in osteoclast cultures free from added osteoblastic
      cells. Tamoxifen, which itself had no effect on bone resorption, appeared to
      antagonise these E2 effects. Although the physiological significance of the
      stimulatory effect is unclear, we hypothesize that its presence prevented us, and
      previous workers, from observing dose-responsive inhibition of bone resorption by
      E2 in vitro.

PMID- 2000699
TI  - Impaired secretion of growth hormone-releasing hormone, growth hormone and IGF-I
      in elderly men.
AB  - The GHRH test and L-dopa test were performed in 12 normal young men (24.1 +/- 1.1
      years) and 12 normal elderly men (77.8 +/- 1.4 years) to investigate age-related
      changes in secretion of GHRH, GH and IGF-I. The basal plasma levels of GHRH and
      GH were not significantly different in young and elderly men, but the basal
      plasma level of IGF-I was higher in the young men (159.0 +/- 11.7 vs 86.7 +/-
      11.6 micrograms/l). The area under the curve for plasma GH in the GHRH test was
      less in the elderly group (35.1 +/- 5.9 vs 11.2 +/- 2.1 micrograms.h-1.l-1, p
      less than 0.001). The AUCs for the plasma GHRH and GH responses in the L-dopa
      test in young and elderly men were 32.0 +/- 2.7 vs 20.3 +/- 1.8 ng.h-1.l-1 (p
      less than 0.001), and 21.8 +/- 4.6 vs 5.4 +/- 1.1 micrograms.h-1.l-1 (p less than
      0.01), respectively, indicating decreased releases of GHRH and GH in the elderly.
      Correlations between the AUCs for plasma GHRH and GH responses in L-dopa were
      found in both groups, but the ratio of the AUCs for GH/GHRH was lower in the
      elderly group. The elderly group showed a significant correlation between the
      basal plasma IGF-I level and the AUCs for plasma GH in the GHRH and L-dopa tests.
      These results suggest that elderly men have a decreased reserve of hypothalamic
      GHRH, resulting in secondarily impaired GH release, which may lead to a lower
      level of IGF-I than in young men.

PMID- 2000700
TI  - The thyroid hormone analogue SKF-94901 and iodothyronine binding sites in
      mammalian tissues: differences in cytoplasmic binding between liver and heart.
AB  - The thyroid hormone analogue, SKF-94901 exhibits greater thyromimetic activity in
      the liver than in the heart. This difference in activity may reflect
      heterogeneity in the affinity of SKF-94901 for different forms of the T3
      receptor. A difference in extranuclear transport of the analogue could also
      account for the different response of these two tissues. To distinguish between
      these possibilities we have examined the binding of SKF-94901 to membrane,
      cytosolic and nuclear preparations from liver and heart of the primate, Macaca
      fascicularis. Uptake of SKF-94901 into H4 liver cells was low. Binding of
      [125I]T3 to cell membrane preparations (Kd approximately 3 mumol/l), and to
      nuclear extracts (Kd approximately 0.2 nmol/l) was displaceable by SKF-94901 with
      a potency 2-5% that of T3 in each case. No significant difference was observed
      between liver and heart for SKF-94901 binding to membranes or nuclear extract.
      With cytosol, [125I]T3 binding was identical in heart (Kd, 22.7 +/- 10.4 nmol/l)
      and liver tissue (Kd, 30.3 +/- 11.1 nmol/l). In liver, and in cardiac cytosol
      after preliminary washing to remove serum, iodothyronine potency was in the order
      T3 greater than T4 greater than rT3. The ratio of SKF-94901 to T3 concentrations
      which gave 50% displacement was 15.9 +/- 6.8 in the liver; and 152.3 +/- 89.1 in
      the heart (p less than 0.05). The selective tissue activity of SKF-94901 may be
      related to a reduced affinity of the analogue for the cytosolic binding proteins
      in the heart, rather than a difference in affinity for various forms of the T3
      receptor.

PMID- 2000701
TI  - Amyloid protein in somatostatinoma differs from human islet amyloid polypeptide.
AB  - Amyloid deposits in somatostatinomas are rare observations. To examine the
      characteristics of this amyloid, we compared amyloid deposits in a
      somatostatinoma to those found in pancreatic tissue in patients with Type II
      diabetes mellitus and in insulinomas, using immunohistochemical techniques and
      specific antibodies to islet amyloid polypeptide or other pancreatic hormones, as
      well as electron-microscopy. Antibodies to islet amyloid polypeptide regions 8-17
      or 25-37 were confirmed to be specific. Amyloid deposits in patients with Type II
      diabetes mellitus and in insulinomas, but not those in the somatostatinoma
      strongly reacted with these antibodies, or to an antibody to amyloid P component.
      Amyloid deposits in the somatostatinoma were not reactive with antibodies to
      somatostatin or to other pancreatic hormones. Electron-microscopic examinations
      revealed that amyloid fibrils in the somatostatinoma were thinner and more
      randomly distributed than were those in islets from patients with Type II
      diabetes mellitus. As amyloid in somatostatinomas is unlike that consisting of
      islet amyloid polypeptide or other mature pancreatic hormones, it may be a novel
      type of local amyloid in pancreatic islets.

PMID- 2000702
TI  - Intracellular calcium and phospholipid turnover are not involved in the
      inhibition of iodothyronine 5'-deiodinase type II activity by T4.
AB  - In glial cell cultures, iodothyronine 5'-deiodinase type II is stimulated by
      dibutyryl cAMP. Serum-free medium increases enzyme activity and prolongs the half
      life of the enzyme. T4 and rT3 specifically inhibit this activity. We tested
      whether enzyme inactivation by T4 was mediated by changes in cytosolic free
      calcium concentration and/or phospholipid turnover. Intracellular calcium
      concentration was decreased either by chelation of extracellular calcium or by
      chelation of extracellular and intracellular calcium. Neither basal hypothyroid
      5'-deiodinase activity nor its inactivation by T4 were modified in such
      experimental conditions, compared with control cells incubated in normal calcium
      containing medium. T4 by itself had no effect on the cytosolic free calcium
      concentration for up to 20 min. Studies on phospholipid turnover included
      norepinephrine in parallel to T4 as positive stimulation control. While
      norepinephrine clearly accelerated phosphoinositide turnover, there was no effect
      of T4 on any phospholipid turnover. These results suggest that neither cytosolic
      free calcium nor phospholipid turnover is involved in T4-dependent modulation of
      5'-deiodinase type II activity in astrocytes in culture.

PMID- 2000703
TI  - Effects of triiodothyronine, dexamethasone and estradiol-17 beta on GH mRNA in
      rat pituitary cells in culture as revealed by in situ hybridization.
AB  - The GH lines of rat pituitary tumour cells have been largely used to study the
      regulation of GH mRNA. In order to investigate the role of T3, dexamethasone and
      estradiol-17 beta on GH expression in non-tumoural pituitary cells, we have used
      in situ hybridization techniques performed on rat anterior pituitary cells in
      monolayer culture. The amounts of mRNA encoding for GH, as evaluated by counting
      the number of grains per somatotrope, were markedly reduced after 4 days of
      culture in a steroid-free medium supplemented with an hypothyroid calf serum.
      Addition of T3 or dexamethasone for 3 days increased GH mRNA levels. The
      concomitant administration of the two hormones produced a synergistic effect on
      GH mRNA levels which became higher than those observed after T3 or dexamethasone
      administration alone. However, this effect did not restore GH mRNA levels to
      those measured in monolayer pituitary cells grown in medium containing 10% fetal
      calf serum. Moreover GH mRNA levels appeared higher in male than in female
      pituitary cells. The administration of E2 to pituitary cell cultures from both
      male and female rats produced an increase by 15, and 12.8% in GH mRNA levels in
      male and female, respectively. This stimulatory effect of E2 in cell culture was
      competitively blocked by simultaneous incubation with the antiestrogen LY156758
      (Keoxifene). These results demonstrate that T3, dexamethasone as well as E2 act
      directly on somatotropic cells to regulate GH gene expression.

PMID- 2000705
TI  - Agency for health care policy and research.

PMID- 2000704
TI  - Sexual dimorphism in renal function and hormonal status of New Zealand
      genetically hypertensive rats.
AB  - Renal water and electrolyte handling and related plasma hormone levels were
      measured in male and female New Zealand genetically hypertensive and normotensive
      rats, in an attempt to establish any potentially important sex-related
      differences in these parameters. Male hypertensive rats had higher blood pressure
      than female hypertensive rats, but normotensive rats showed no such sex
      difference. Both groups of males had higher fluid turnover rates than respective
      females, and this was associated with raised plasma vasopressin in hypertensive
      males. Female hypertensive rats excreted more sodium, potassium and chloride in
      association with lower plasma aldosterone and higher corticosterone levels
      compared with the other groups. Plasma electrolytes did not differ between the
      four groups, but plasma osmolality was higher in hypertensive than normotensive
      rats of both sexes. A higher rate of electrolyte loss and lower fluid turnover in
      association with reduced plasma vasopressin may contribute to the lower blood
      pressure of female compared with male hypertensive rats.

PMID- 2000706
TI  - A style change for the AANA Journal.

PMID- 2000707
TI  - Pennsylvania Blue Shield agrees to reimburse nurse anesthetists.

PMID- 2000709
TI  - Propofol causes a burning sensation on injection.

PMID- 2000708
TI  - AANA Journal course: new technologies in anesthesia: update for nurse
      anesthetists--a look to the future--transdermal and transmucosal administration
      of anesthetic drugs.
AB  - Recent developments in both applied dermal physiology and in pharmaceutical
      technology are paving the way toward the introduction of novel routes of drug
      administration into anesthetic practice. Among these approaches, transdermal and
      transmucosal applications have shown particular promise in clinical trials all
      over the world. The emergence of new drug administration techniques that help to
      improve drug compliance, enhance safety and diminish both physical and
      psychological trauma will prove to be desirable additions to the anesthetist's
      armamentarium. This installment of the AANA Journal course will explore the
      latest developments in these areas destined to have a significant impact on the
      nurse anesthetist's clinical practice.

PMID- 2000710
TI  - Anesthetic considerations for the postcardiac transplant patient.
AB  - The first human heart transplant was performed in 1967. The low survival rates of
      the early transplant patients revealed that the surgical procedure was only a
      small part of successfully managing these patients. Patient outcome depended upon
      the interrelationship of surgery, immunology, pharmacology, epidemiology and
      oncology. A comprehensive understanding of the transplanted heart is essential to
      effectively plan the anesthetic management of posttransplant patients requiring
      any type of surgery. The transplant recipient has a healthy heart which utilizes
      different mechanisms to meet the body's requirements. The autonomic regulatory
      mechanisms are not available to prevent wide swings in the patient's hemodynamic
      state, and the stress response is slower than normally expected. Since cardiac
      parameters are significantly altered, patients may demonstrate decreases in
      systemic blood pressure and cardiac filling pressures. Compensatory maneuvers are
      delayed and reductions in cardiac output lead to lessened cerebral perfusion.
      Anesthetists must allow time for the denervated heart to compensate for these
      changes. Pharmacologic intervention should consist of drugs with direct action on
      the myocardium and vasculature. Posttransplant patients are immunosuppressed and
      maintenance of a delicate balance is essential for survival. Protocols for
      immunosuppressive therapy must be individualized to achieve optimal effects.
      Cyclosporine plays a major role in immune system depression. Anesthetic
      management must compensate for alterations in hepatic and renal function,
      vascular integrity and cardiac function. Strict adherence to aseptic technique
      helps reduce infections related to anesthesia management.

PMID- 2000711
TI  - The history of nurse anesthesia education: highlights and influences.
AB  - The history of nurse anesthesia is traced from its beginnings at the turn of the
      century to the present. The crucial role of the military in the profession's
      growth is explored. The sequence of events leading up to AANA's founding in 1939
      are recounted. With the profession's often-contentious relationship with the
      anesthesiologists as a recurrent theme, AANA's strides in enhancing the rights
      and stature of its members are examined.

PMID- 2000712
TI  - Results of a survey of nurse anesthesia education programs: diversity, growth and
      regionalization.
AB  - This survey was conducted in June of 1990. Questionnaires were sent to and data
      obtained from all civilian and military nurse anesthesia education programs.
      Programs were asked to provide the following information: type of conducting
      institution; the party responsible for the administrative costs of the program;
      name and location of the program's academic affiliation; the name, location, type
      and purpose of all clinical affiliations/sites; and distance from the conducting
      institution to the academic affiliation and to each clinical site. The conducting
      entities for civilian programs were as follows: hospital or medical center, 43
      programs; academic institution, 15 programs; joint arrangement between a hospital
      and an academic institution, 10 programs; freestanding, 4 programs; other, 7
      programs. For purposes of this survey, each branch of the military was considered
      to have a single program with multiple clinical sites. Two military programs
      identified their conducting entity as a joint arrangement between the respective
      branch of the military and an academic institution. The third program identified
      itself as freestanding with an academic affiliation. In all but seven programs,
      the administrative costs of the program are the responsibility of the conducting
      institution. The majority of programs (74%) have an academic affiliation and 68%
      of programs offer a graduate degree. Eighty percent of programs with an academic
      affiliation are located within 50 miles of the academic site. The greatest
      distance between a program and its academic affiliation is 350 miles. Programs
      reported having from 1-13 clinical sites (mean = 3.6 sites/program). Military
      programs, freestanding programs and programs conducted by an academic institution
      have the highest mean number of sites per program.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 2000713
TI  - Regionalized education and the accreditation process.
AB  - The concept of regionalized education is discussed in relation to its application
      to nurse anesthesia education. New approaches to the existing process of
      accreditation are proposed to facilitate this new system of delivery. The Council
      on Accreditation is seen as the body that should take a leadership role in
      bringing about change.

PMID- 2000714
TI  - Nurse anesthesia: evolution of the first New England regional graduate program.
AB  - The conversion of a newly accredited, hospital-based, certificate nurse
      anesthesia program into a 29-month regionalized graduate program is described.
      Students who complete the program receive an MS degree in biology nurse
      anesthesia. A concurrent degree track is offered to CRNAs who hold a
      baccalaureate degree.

PMID- 2000715
TI  - Neuromuscular blockade: electromyographic and mechanical versus visual
      interpretation.
AB  - Anesthetists frequently provide intraoperative muscle relaxation in addition to
      general anesthesia. However, visual interpretation of the effect of neuromuscular
      blocking drugs is not always possible. This study examined two alternative
      methods (electromyography/electrocardiography [EMG/ECG] and mechanical/ECG) of
      interpreting neuromuscular blockade and compared these methods to visual
      interpretation. EMG/ECG and mechanical/ECG methodologies were found to provide
      reliable valid intraoperative interpretation of nondepolarizing neuromuscular
      blockade for single-twitch and train-of-four stimuli. EMG/ECG and mechanical/ECG
      measures of neuromuscular blockade were performed with an electrocardiographic
      monitor and a pressure transducer, respectively. Both EMG/ECG and mechanical/ECG,
      when compared to visual interpretation, were found to be equally, and usually
      more, valid indicators of neuromuscular blockade. The clinical significance of
      this study is its contribution to quality care and patient safety. When visual
      monitoring of neuromuscular blockade is not feasible, either EMG/ECG or
      mechanical/ECG provide an alternative method of monitoring neuromuscular
      blockade.

PMID- 2000716
TI  - Course of HIV infection in homosexual and bisexual men.

PMID- 2000718
TI  - AHA issues new report on endocarditis prophylaxis.

PMID- 2000717
TI  - Nationwide vaccine adverse events reporting system.

PMID- 2000719
TI  - HIV antibody screening of women and newborns.

PMID- 2000720
TI  - IVIG for children with HIV infection.

PMID- 2000721
TI  - Health care for America's poor.

PMID- 2000722
TI  - Secondary hemochromatosis: diagnosis by MRI.

PMID- 2000723
TI  - Diagnosis of occult prostate cancer.

PMID- 2000724
TI  - Call for physician assistance.

PMID- 2000725
TI  - My first diagnosis.

PMID- 2000727
TI  - Family practice perspective.

PMID- 2000726
TI  - New guidelines for prevention of bacterial endocarditis.

PMID- 2000728
TI  - New developments in cardiopulmonary resuscitation.
AB  - Since the last revision of the American Heart Association's guidelines in 1985,
      several new developments of clinical importance have occurred in the field of
      cardiopulmonary resuscitation. These include enhanced access to and earlier use
      of defibrillation, the use of high-dose epinephrine when standard doses fail, the
      assessment of resuscitative efforts with end-tidal CO2 monitoring and the
      addition of two new drugs, amiodarone (for refractory ventricular fibrillation)
      and adenosine (for paroxysmal supraventricular tachycardia). Time will determine
      the ultimate role of these advancements in the management of cardiac arrest.

PMID- 2000729
TI  - Choosing an antidepressant to treat depression.
AB  - Depression refers to both a symptom and a potentially life-threatening illness.
      Most patients with depression are seen by primary care physicians. Antidepressant
      medications are effective in up to 85 percent of patients with major depression.
      Most antidepressants tend to be equally effective. Drug selection is usually
      based on minimizing or taking advantage of certain side effects, including
      sedation and anticholinergic and cardiovascular effects. Some characteristics of
      patients, such as suicide potential, pregnancy, age and medical illness, also
      affect the choice of drug.

PMID- 2000730
TI  - Gastroesophageal reflux in infants.
AB  - Clinically significant gastroesophageal reflux occurs in one in 500 infants.
      Symptoms resolve in 60 to 80 percent of infants by 18 months of age. Thickened
      formula and position changes are often recommended. Medication and surgical
      intervention may be needed in refractory cases.

PMID- 2000731
TI  - Preventive health care for the adolescent.
AB  - Adolescents represent the only segment of the population with an increasing
      mortality rate. The majority of deaths are due to accidents, homicide and
      suicide. The risks for these events are associated with developing sexuality and
      the use of drugs and alcohol. Behaviors that put the young person's future health
      at risk, such as poor nutritional habits, the use of tobacco and lack of
      exercise, are often established during adolescence. Surveillance of risk and
      interventions to prevent problems are critical activities for the family
      physician.

PMID- 2000732
TI  - Giant cell tumor of bone.
AB  - Giant cell tumor is the second most common benign tumor of bone. Plain
      radiographs may demonstrate distinctive features but can also be misleading. The
      diagnosis may be aided by the use of other imaging modalities, such as bone scan,
      computed tomography and angiography. The recurrence rate is high, but some of the
      newer treatments seem to be associated with better outcomes.

PMID- 2000733
TI  - Selective fallopian tube canalization.
AB  - Infertility is an increasingly common problem. Occlusion of the fallopian tubes
      is one of the principal causes, and until recently surgery was the only available
      treatment. The success rate of surgery is often low, particularly with occlusion
      of the proximal tube. Selective fallopian tube canalization under fluoroscopic
      guidance has been successful in alleviating proximal tubal obstruction. This
      procedure may be performed in the outpatient setting and is a safe, cost
      effective alternative to surgery.

PMID- 2000734
TI  - Treatment of traumatic peripheral nerve injury.
AB  - Peripheral nerve injuries are caused by traction, laceration and missile injury.
      Primary surgical repair is recommended for clean, sharp injuries that cause
      transection of a nerve. In compressed, stretched or contused nerves, surgical
      repair at three months is indicated if functional recovery has not occurred.
      Electromyography and nerve conduction studies are helpful in deciding which
      patients need secondary repair. Recovery is possible for 18 months following
      injury. Since nerve regeneration occurs at a rate of one inch per month, the
      distance from the nerve injury to the innervated muscle must be less than 18
      inches. Therefore, the outcome is generally better in distal lesions than in
      proximal ones.

PMID- 2000735
TI  - PUVA therapy.
AB  - PUVA is an acronym for psoralen plus ultraviolet-A radiation. This form of
      photochemical therapy is commonly used in the treatment of psoriasis and
      vitiligo, but it is also beneficial in other dermatologic diseases. An
      understanding of psoralen's mechanism of action and the unique properties of the
      various psoralen preparations is important in ensuring optimal results with this
      therapy.

PMID- 2000736
TI  - Cephalosporins: rationale for clinical use.
AB  - Cephalosporins, the most widely used class of antibiotics, are more resistant
      than penicillins to inactivation by beta-lactamases. Based on their spectrum of
      activity against gram-negative bacteria, cephalosporins are classified into three
      generations. The generation classification, however, does not correlate with
      activity against gram-positive bacteria or anaerobes. First-generation
      cephalosporins have a narrow gram-negative spectrum but are most active against
      gram-positive bacteria, particularly Staphylococcus aureus. Third-generation
      compounds have excellent activity against gram-negative bacteria. The
      cephamycins, a second-generation subgroup that includes cefoxitin, cefotetan and
      cefmetazole, have the best activity against anaerobes.

PMID- 2000737
TI  - Reduced dosage of zidovudine in patients with AIDS.

PMID- 2000738
TI  - Safety and efficacy of urokinase during elective coronary angioplasty.
AB  - Eighty-nine of 462 patients were treated with adjunctive urokinase during
      elective percutaneous transluminal coronary angioplasty (PTCA), 26% for unstable
      angina, 34% for intracoronary thrombus, 27% for intimal dissection, 10% for
      abrupt closure, and 3% for saphenous vein graft embolism. The 80 patients treated
      before abrupt closure (group A) were compared with 167 patients with similar
      profiles who did not receive urokinase (group B). Procedural success rates were
      similar. Adverse cardiac events (abrupt closure, myocardial infarction, emergency
      coronary artery bypass, or death) in group A versus group B occurred in: 1 of 30
      (3%) versus 5 of 27 (18.5%) (p = 0.07) with intracoronary thrombus, 5 of 45 (9%)
      versus 18 of 110 (16.3%) with unstable angina, 1 of 12 (8%) versus 4 of 13 (31%)
      with unstable angina with intracoronary thrombus, 4 of 33 (12%) versus 14 of 97
      (14.4%) with unstable angina without intracoronary thrombus, and 5 of 24 (20.8%)
      versus 6 of 66 (9%) with intimal dissection. Hemorrhagic complications occurred
      in 11% of patients who were treated with urokinase versus 9% of patients who were
      not (p = NS). No difference in blood transfusions existed. Thus urokinase was
      found to be safe during elective PTCA. In patients with intracoronary thrombus,
      urokinase appears to decrease the incidence of new adverse cardiac events,
      whereas in patients with intimal dissection it might have an adverse effect.

PMID- 2000739
TI  - Late streptokinase infusion and antithrombotic treatment in myocardial infarction
      reduce subsequent myocardial ischemia.
AB  - Of 255 consecutive patients with acute myocardial infarction, 111 were eligible
      for attempted late thrombolysis. They were randomly assigned to either
      thrombolytic and antithrombotic treatment (treatment group) or routine treatment
      (control group). Patients in the treatment group received streptokinase initiated
      late (mean 32 hours; range 12 to 49) after the onset of symptoms, followed by
      heparin infusion for at least 5 days and warfarin and dipyridamole for at least 3
      months. Patients were examined clinically and by bicycle ergometry on discharge
      from the hospital and after 3 and 12 months. The two groups did not differ with
      respect to deaths or reinfarctions. There was a trend toward a lower incidence of
      angina pectoris in the treatment group. Exercise tolerance in this group was
      significantly higher than in the control group (at 3 months 124 +/- 39 W vs 107
      +/- 41 W; p less than 0.05). The difference was entirely accounted for by
      patients with no previous history of infarction or angina pectoris (at 3 months
      142 +/- 37 W vs 112 +/- 45 W; p = 0.01). ECG signs of myocardial ischemia, silent
      or symptomatic, occurred at significantly lower levels of exercise among patients
      in the control group compared with patients in the treatment group. The results
      support the notion that thrombolytic therapy given as late as 12 to 49 hours
      after the onset of symptoms may reduce the incidence of residual ischemia during
      the postinfarction period.

PMID- 2000740
TI  - Impedance measurement of absolute blood flow using an angioplasty catheter: a
      validation study.
AB  - An angioplasty catheter was developed to allow measurement of absolute coronary
      blood flow during interventional procedures. This method uses electrical
      impedance changes induced by a 0.5 ml bolus of 5% dextrose solution and indicator
      dilution principles. The indicator is injected through a port located just
      proximal to the dilating balloon and the resulting changes in blood impedance are
      measured by electrodes at the catheter tip. Excellent linear correlations were
      found between known flow in 2 to 4 mm to diameter plastic tubes and catheter
      measurements (r = 0.99) and between timed collection canine femoral artery flow
      and catheter measurements (r = 0.97). Final validation was performed in canine
      coronary arteries using electromagnetic flowmeter data as the standard (r =
      0.94). Thus accurate clinical determination of absolute coronary blood flow can
      be accomplished using this relatively inexpensive and simple catheter technique.

PMID- 2000741
TI  - Immediate regional endocardial surface expansion following coronary occlusion in
      the canine left ventricle: disproportionate effects of anterior versus inferior
      ischemia.
AB  - The exact time of onset of functional expansion after acute myocardial
      infarction/ischemia remains unclear in spite of its potential link to chronic
      pathologic infarct expansion and its potential implications for therapy. To
      examine this early change in ventricular morphology, 14 open-chest dogs were
      studied with two-dimensional echocardiography before and after occlusion (10
      minutes) of the left anterior descending coronary artery (LAD, n = 7) or
      circumflex artery (CIRC, n = 7). The endocardial surface area (ESA) and the area
      of abnormal wall motion (AWM) were reconstructed from the echocardiographic data
      using a previously reported technique for quantitatively mapping the ESA and
      extent of AWM. For the total group (N = 14), the mean ESA before occlusion was
      48.9 +/- 9.8 cm2, increasing to 65.7 +/- 18.9 cm2 at 10 minutes occlusion (p less
      than 0.001). For the LAD subgroup, the mean ESA before occlusion was 50.7 +/- 9.3
      cm2, increasing to 79.1 +/- 14.1 cm2 at 10 minutes following occlusion (p less
      than 0.001). For the CIRC subgroup, the mean ESA before occlusion was 47.1 +/-
      10.8 cm2, increasing to 52.3 +/- 12.6 cm2 at 10 minutes after occlusion (p less
      than 0.001). The ESA increase for the LAD subgroup was significantly larger than
      that of the CIRC subgroup (LAD range 14.5 to 49.9 cm2 versus CIRC range 1.5 to 9
      cm2, p less than 0.0001). Coronary occlusion resulted in similarly sized regions
      of AWM for both subgroups (LAD, 31.3 +/- 12.2 cm2 versus CIRC, 25.9 +/- 10.3 cm2,
      p = n.s.). For the LAD group, the largest increase in endocardial circumference
      occurred within the zone of AWM at the apex (39.9 +/- 12%). The endocardial
      surface area therefore expands immediately after coronary occlusion and the
      magnitude of this process is primarily related to the site (anteroapical) rather
      than to the extent of AWM.

PMID- 2000742
TI  - Detection of myocardial infarction in the presence of Wolff-Parkinson-White
      syndrome by QRST isoarea map in dogs.
AB  - The possibility of detecting myocardial infarction (MI) in the presence of Wolff
      Parkinson-White (WPW) syndrome by means of body surface QRST isoarea maps was
      studied in eight dogs. Eighty-seven body surface ECGs were recorded
      simultaneously. Recordings were taken during right atrial (RA) and right atrial
      and right ventricular (RA + RV) sequential pacing, which simulated WPW syndrome,
      during control periods and at 1-hour intervals for up to 5 hours after occlusion
      of the left anterior descending coronary artery. In ECGs during the RA drive,
      diagnostic findings of MI such as abnormal Q waves were observed but became
      obscure during the RA + RV drive. On the contrary, the QRST values over the
      anterior chest during both drives were positive soon after coronary occlusion,
      decreased gradually as time passed, and became abnormally negative after 5 hours.
      The QRST isoarea maps during RA and RA + RV pacing showed quite similar patterns
      and were highly correlated with each other throughout this study (r greater than
      0.95). These findings demonstrate that localized abnormalities resulting from MI
      are evident in QRST isoarea maps even in the presence of preexcitation and
      fusion.

PMID- 2000743
TI  - Acute reduction of mitral valve area after percutaneous balloon mitral
      valvuloplasty: assessment with Doppler continuity equation method.
AB  - Mitral valve areas before and after balloon mitral valvuloplasty were serially
      determined by the Doppler continuity equation method in 16 patients. Ultrasound
      examinations were performed before and immediately after balloon inflation and 24
      hours, 1 week, and 1 month after valvuloplasty. Mitral valve area determined by
      the Doppler continuity equation method correlated well with that determined at
      catheterization by the Gorlin formula, not only before but also immediately after
      balloon inflation (y = 0.87 x + 0.05, standard error of estimate = 0.22 cm2, r =
      0.90). Serial calculation of mitral valve area by the Doppler continuity equation
      method showed a slight but significant decrease in the valve area at 24 hours
      after balloon mitral valvuloplasty but no change after that. We conclude that the
      Doppler continuity equation method provides an accurate estimation of mitral
      valve area before and even after balloon valvuloplasty. Mitral valve area dilated
      by balloon inflation is decreased slightly within 24 hours after the procedure,
      which corroborates valve stretch as one mechanism for increasing mitral valve
      area with balloon valvuloplasty. Estimation of mitral valve area immediately
      after balloon mitral valvuloplasty may overestimate the long-term efficacy of the
      procedure.

PMID- 2000744
TI  - Acute hemodynamic effects of intravenous diperdipine, a new dihydropyridine
      derivative, in coronary heart disease.
AB  - The acute hemodynamic effects of a new dihydropyridine calcium channel blocker,
      diperdipine, which is suitable for intravenous administration, were studied by
      right and left cardiac catheterization in 16 patients with coronary heart
      disease. Diperdipine markedly reduced systemic vascular resistance and improved
      stroke index and left ventricular ejection fraction. Mean pulmonary artery and
      wedge pressures were slightly increased as a possible consequence of enhanced
      venous return, whereas right atrial and left ventricular end-diastolic pressures
      were not significantly changed. Nevertheless, an increase in preload was clearly
      indicated by an augmented left ventricular end-diastolic volume index after
      administration of diperdipine. Left ventricular contractility, which was
      estimated by the end-systolic pressure-volume ratio and by dP/dt max was not
      significantly changed, though analysis of individual data suggests a minimally
      negative inotropic effect. However, such a minor effect on left ventricular
      contractility was largely counterbalanced by the marked reduction of afterload,
      which produced a sharp improvement of stroke index. Enhancement of left
      ventricular ejection fraction and reduction in systemic vascular resistance were
      inversely and directly correlated to control values. Overall, diperdipine was
      well tolerated, but one patient had a major untoward reaction that consisted of
      an ischemic episode that was possibly related to drug administration. In
      conclusion, intravenous diperdipine appears to be a potent arteriolar dilating
      agent that does not affect left ventricular contractility.

PMID- 2000745
TI  - Improvement of systolic and diastolic left ventricular wall motion by serial
      echocardiograms in selected patients treated for unstable angina.
AB  - The purpose of the study was to evaluate the effect of antiischemic treatment on
      left ventricular function in selected patients with unstable angina pectoris that
      was due to severe proximal left anterior descending coronary artery narrowing and
      to identify subgroups liable to an adverse outcome (mean term 2.7 years). Effect
      of antiischemic treatment on systolic and diastolic left ventricular wall motion
      was studied in 35 patients who had unstable angina pectoris and an
      electrocardiogram that indicated severe proximal left anterior descending
      coronary artery narrowing. Treatment consisted of either a revascularization
      procedure (17 patients) or antianginal drug therapy (18 patients). All patients
      underwent a two-dimensional echocardiographic study within 48 hours (mean 20
      hours) of entry into the study. This study semiquantitatively analyzed systolic
      performance of the ischemia-related segments by calculation of a total wall
      motion score. In 16 patients this investigation was combined with a continuous
      detailed recording of only the apical interventricular septal wall motion. This
      detailed study included measurements for regional function by providing a
      typification of the pattern of systolic and early diastolic excursion of the
      endocardial border of the apical interventricular septum. A repeat ultrasonic
      study was performed at least 1 month (median 2 months, 7 days) after admission.
      Results of the systolic wall motion analyses of all 35 patients showed, in both
      treatment groups, a significant improvement in systolic wall motion of the
      anterior and apical segments (mean total wall motion score at early study vs late
      study: revascularization, 6.9 vs 2.2 and medical therapy, 4.6 vs 1.0).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 2000746
TI  - Collateral circulation in Kawasaki disease with coronary occlusion or severe
      stenosis.
AB  - Forty patients with Kawasaki disease with severe coronary sequelae were
      investigated. All had at least a 90% reduction in the diameter of the major
      coronary artery. Collateral vessels were seen in 32 of 33 (97%) patients with
      total occlusion. All patients with severe stenosis but not total occlusion had no
      or poorly developed collateral vessels. Analysis according to the presence or
      absence of collateral vessels showed no significant differences in the results of
      treadmill stress testing and myocardial imaging between these two groups. In
      patients treated surgically, the abnormalities recognized by these tests were
      normalized or improved when the bypass was patent. These data indicate that
      collateral circulation in patients with Kawasaki disease cannot be seen
      angiographically unless there is total occlusion and the presence of collateral
      circulation cannot provide protection against stress-induced myocardial ischemia.

PMID- 2000747
TI  - Histologic abnormalities of large and small coronary arteries, neural structures,
      and the conduction system of the heart found in postmortem studies of individuals
      dying from the toxic oil syndrome.
AB  - Hundreds died and thousands were poisoned by rapeseed oil adulterated with
      aniline and sold illegally in Spain in 1981. The clinical manifestations, now
      known as the toxic oil syndrome, include pulmonary hypertension and right
      ventricular hypertrophy plus widespread vascular and neural lesions in other
      organs. Many of the late deaths ended with a scleroderma-like illness. Because
      scleroderma involves the heart, in this study we examined the small and large
      coronary arteries, neural structures, and conduction system from eight victims
      dying with the toxic oil syndrome. Dense fibrosis of the sinus node in two hearts
      resembled changes found in scleroderma. Atrionodal junctional hemorrhages and
      cystic degeneration of the sinus node present in the other six hearts resembled
      changes found in lupus erythematosus. Small and large coronary arteries exhibited
      focal fibromuscular dysplasia and a proliferative cystic myointimal degeneration.
      This latter abnormality was associated with sloughing of the inner wall and
      embolization of the detached fragment downstream in the same coronary artery.
      Every heart had many degenerative lesions within nerves, ganglia, and the
      coronary chemoreceptor. Both the arterial and neural abnormalities prominently
      involved the conduction system. Based upon observations by others with
      experimental feeding of rapeseed oil containing either high or low erucic acid,
      we suggest that this oil must remain a major suspected cause of the toxic oil
      syndrome, particularly in conjunction with some as yet unexplained facilitative
      influence by oleoanilids. If this is so, it is important to reconsider the widely
      recommended use of any rapeseed oil product as a suitable food for man or other
      animals.

PMID- 2000748
TI  - Time course of improvement in ventricular function after ablation of incessant
      automatic atrial tachycardia.
AB  - A patient with dilated cardiomyopathy and supraventricular tachycardia presumed
      to be of sinus origin was referred for cardiac transplantation. The extreme rate
      of the tachycardia during exercise, profound fluctuations in heart rate, and the
      presence of an abnormal P wave axis suggested the diagnosis of incessant ectopic
      atrial tachycardia rather than compensatory sinus tachycardia. Electrophysiologic
      study with endocardial activation sequence mapping confirmed the diagnosis of an
      ectopic left atrial automatic tachycardia, after which surgical cryoablation of
      the left atrial focus was carried out successfully and sinus rhythm was restored.
      Serial radionuclide angiocardiograms obtained before and after surgery
      demonstrated a very rapid recovery of left ventricular function to nearly normal
      within the first month after surgery, followed by further improvement to normal
      over the next several months. The diagnosis of tachycardia-related cardiomyopathy
      should be seriously considered in any patient with apparently end-stage dilated
      cardiomyopathy and persistent resting tachycardia.

PMID- 2000749
TI  - Identification of the rate-dependent functional refractory period of the
      atrioventricular node in simulated atrial fibrillation.
AB  - We continuously observed successive pairs of R-R intervals during atrial
      fibrillation and hypothesized that the shortest R-R interval for a given
      preceding R-R interval in a pair represents the functional refractory period of
      the atrioventricular node at that preceding interval. To test this hypothesis we
      simulated atrial fibrillation in 28 isolated cross-perfused canine hearts and
      obtained an R-R interval scatterplot by plotting the R-R intervals as a function
      of the immediately preceding R-R interval. This scatterplot enabled us to detect
      a series of the shortest R-R intervals for a wide range of preceding R-R
      intervals, and this allowed us to estimate the rate-dependent functional
      refractory period of the atrioventricular node in simulated atrial fibrillation.
      The estimated functional refractory periods correlated well with those measured
      by the conventional method (r = 0.93). We conclude that the proposed method makes
      it possible to estimate the rate-dependent functional refractory periods of the
      atrioventricular node in atrial fibrillation.

PMID- 2000750
TI  - Septal ventricular pacing in the immature canine heart: a new perspective.
AB  - Cardiac pacing initiated from epicardial or transvenous apical right ventricular
      electrodes causes asynchronous ventricular contraction. This alters myocardial
      stress vectors and results in adverse cellular and subcellular changes in the
      experimental animal. Clinically, such changes may contribute to the adverse
      hemodynamics reported with long-term ventricular pacing. To determine the
      feasibility of direct stimulation of the ventricular specialized conduction
      systems and therefore the potential for maintenance of normalized depolarization
      patterns, 13 beagle puppies were studied. Baseline ventricular activation and
      contraction patterns were obtained using intracardiac electrograms and multigated
      nuclear acquisition (MUGA) imaging. Septal electrode insertion from the
      aortoatrial groove was accomplished by use of two-dimensional echocardiography
      and continuous electrocardiographic (ECG) monitoring of the surface ECG during
      pacemaker implantation in five puppies. Standard right ventricular epicardial
      electrodes were implanted in five additional animals, with three remaining as age
      matched non-paced controls. After 4 months of observation, repeat MUGA imaging
      and intracardiac electrograms demonstrated nearly normal biventricular activation
      and contraction patterns among the septal-paced group. Histopathologic
      examination illustrated normal cellular morphology in the septal-paced animals.
      This study demonstrates that pacing electrode insertion into the proximal
      interventricular septum is feasible and results in utilization of the normal
      ventricular conduction pathway. Such an approach to initiation of ventricular
      stimulation may attenuate the adverse effects of long-term ventricular pacing.

PMID- 2000751
TI  - Effect of nisoldipine on hemodynamic responses to defibrillation.
AB  - Sequences of ventricular fibrillation-defibrillation cause transient
      hypertension; we hypothesized that this "adrenergic overshoot" might be blunted
      by the functional antiadrenergic effect of the calcium channel blocking drug
      nisoldipine, with a potentially beneficial reduction in myocardial oxygen
      requirements. However, other calcium channel blocking drugs have been shown to
      reduce shock success for defibrillation, a deleterious effect. Thus the purposes
      of this study were to assess the effect of nisoldipine on the hemodynamic
      responses to the sequences of ventricular fibrillation-defibrillation, and its
      effect on the energy requirements for defibrillation. In 16 dogs we administered
      intravenous nisoldipine (1 microgram/kg bolus followed by an infusion of 0.075 to
      0.50 microgram/kg/min) to lower mean blood pressure 10% and 20% below baseline.
      Ventricular fibrillation was induced electrically, and shocks of varying energy
      levels (30, 50, and 100 joules) were administered to determine defibrillation
      energy requirements. Heart rates and blood pressures were recorded up to 3
      minutes after each shock to determine hemodynamic responses. Measurements were
      made before nisoldipine administration and again at the two levels of drug
      induced blood pressure decline. We found that the usual systolic blood pressure
      "overshoot" after defibrillation (typically maximum at 15 to 30 seconds after
      shocks) was significantly blunted after nisoldipine administration (p less than
      0.05). Heart rate slowing after defibrillation (a cholinergic response) was not
      affected. Nisoldipine did not alter shock success rates, which varied from 12 +/-
      7%SE at 30 joules to 68 +/- 12% at 100 joules. Thus nisoldipine blunted the
      "adrenergic overshoot" of systolic blood pressure following defibrillation, a
      potentially beneficial effect, without altering the energy requirements for
      transthoracic defibrillation.

PMID- 2000752
TI  - The effects of high (sodium meglumine diatrizoate, Renografin-76) and low osmolar
      (sodium meglumine ioxaglate, Hexabrix) radiographic contrast media on diastolic
      function during left ventriculography in patients.
AB  - Although a majority of studies indicate superior hemodynamic and clinical
      profiles of low osmolar compared with high osmolar contrast media, the effect of
      these agents on diastolic left ventricular function has not been examined. We
      prospectively examined hemodynamic, electrocardiographic, and echocardiographic
      indices of left ventricular function in patients undergoing contrast
      ventriculography with a high osmolar, ionic, monomeric contrast, diatrizoate
      (Renografin-76) compared with a low osmolar, ionic, dimeric contrast, ioxaglate
      (Hexabrix). Thirty patients were randomized to each group. There were no clinical
      differences between the two groups. The decrease in systemic pressures was
      significantly greater with diatrizoate after left ventriculography (-38.5 +/- 3.5
      versus -18.2 +/- 2.3, p less than 0.001) and selective left coronary angiography
      (-29.5 +/- 2.4 versus -17.4 +/- 2.6, p less than 0.001). In addition, left
      ventricular end-diastolic pressure increased significantly more with diatrizoate
      (7.3 +/- 0.9 versus 2.7 +/- 0.8 mm Hg for ioxaglate, p less than 0.001). QT
      interval prolongation occurred in both patient groups. Diatrizoate decreased
      systemic vascular resistance, and increased cardiac output and left ventricular
      ejection fraction more than ioxaglate, while simultaneously increasing left
      ventricular end-diastolic volume and altering the peak atrial filling velocity.
      Negative dp/dt (p less than 0.05), but not Tau, computed by the logarithmic or
      derivative methods, was reduced by diatrizoate. These data indicate that
      significant alteration of diastolic filling patterns occurs with high osmolar
      compared with low osmolar contrast agents. Although the clinical significance of
      this observation is currently unknown, these data further support the reported
      hemodynamic superiority of the low osmolar, dimeric contrast agent ioxaglate
      during contrast angiography.

PMID- 2000753
TI  - Noninvasive estimation of left atrial pressure in patients with congestive heart
      failure and mitral regurgitation by Doppler echocardiography.
AB  - A completely noninvasive method for estimating left atrial pressure in patients
      with congestive heart failure and mitral regurgitation has been devised with the
      use of continuous-wave Doppler echocardiography and brachial sphygmomanometry. Of
      46 patients studied with mitral regurgitation, 35 (76%) had jets with distinct
      Doppler spectral envelopes recorded. The peak ventriculoatrial gradient was
      obtained by measuring peak mitral regurgitant velocity in systole and using the
      modified Bernoulli equation. This gradient was then subtracted from peak brachial
      systolic blood pressure, an estimate of left ventricular systolic pressure, to
      yield left atrial pressure (left atrial pressure = systolic blood pressure -
      mitral regurgitant pressure gradient). Noninvasive estimates of left atrial
      pressure from 35 patients were plotted against simultaneous recordings of mean
      pulmonary capillary wedge pressure resulting in the correlation y = 0.88x + 3.3,
      r = 0.88, standard error of estimate = +/- 4 mm Hg (p less than 0.001).
      Therefore, continuous-wave Doppler echocardiography and sphygmomanometry may be
      used in selected patients with congestive heart failure and mitral regurgitation
      for noninvasive estimation of left atrial pressure.

PMID- 2000754
TI  - Left atrial volume determination by biplane two-dimensional echocardiography:
      validation by cine computed tomography.
AB  - Left atrial (LA) volume measurements have been made by the application of the
      method of discs (modified Simpson's rule) to orthogonal biplane atrial
      echocardiographic images. Validation of the technique has been suboptimal due to
      deficiencies of the reference standard, levophase angiography. To define the
      accuracy of echocardiography, we compared LA end-systolic volume by
      echocardiography in 27 patients with volumes by cine computed tomography (Cine
      CT), a highly accurate and validated method of measuring cardiac chambers.
      Echocardiographic tracings were made in the apical long-axis two- and four
      chamber views. In patients with atria less than 300 ml, 14 had echoes performed
      prospectively, with optimization of LA size, while the remaining 10 were analyzed
      retrospectively. The volume of each slice was calculated and was then summated to
      obtain total volume. The correlation coefficient between two-dimensional
      echocardiography and Cine CT was r = 0.98, and it was r = 0.82 when patients with
      atria greater than 300 ml (n = 3) were excluded. Echocardiography underestimated
      Cine CT measurements by 23%. The slope of the prospective group was closer to
      unity than the slope of the retrospective group (p less than 0.001), and the
      correlation with Cine CT was slightly better for the prospective group (r = 0.88
      versus r = 0.77). LA volume by two-dimensional echocardiography correlates
      closely with Cine CT, a more accurate method of volume determination, and gives
      valid measurements of LA volume. Efforts to maximize LA size during scanning
      limit inaccuracies of echocardiographic measurements of the left atrium.

PMID- 2000755
TI  - Coronary collateral recruitment: functional significance and relation to rate of
      vessel closure.
AB  - Studies in animals and humans have demonstrated the anatomic presence and
      functional significance of coronary collaterals. The extent of collateralization
      varies among species and among individuals. Collateral vessels are usually
      adequate for preserving resting regional and global ventricular function in the
      face of coronary obstruction. During stress, however, collateral supply may be
      inadequate. Collateral development is a time-dependent process during both the
      initial occlusion and following transient reflow and reclosure. Therefore when a
      previously collateralized coronary occlusion is recanalized and then recloses,
      the extent of the resulting collateral recruitment will depend, at least in part,
      upon the period of reflow between the two occlusions. The longer the reflow
      period, the less enhanced will be the collateralization. This is illustrated in
      the cases presented and has also been demonstrated in animal studies. The exact
      mechanisms for this recurrent collateral recruitment need further study.

PMID- 2000756
TI  - Extraction of implanted transvenous pacing leads: a review of a persistent
      clinical problem.
AB  - Within a few months of implantation, permanent pacemaker leads become ensheathed
      in fibrocollagenous tissue. This tissue may anchor the lead so that it is
      difficult, dangerous, or impossible to remove it. Leads with bulbous or finned
      tips are particularly resistant to extraction. The risks of applying traction to
      an entrapped lead include induction of bradycardia or ventricular tachycardia and
      fibrillation, invagination of the right ventricle, avulsion of the right
      ventricular myocardium or tricuspid valve, hemopericardium, and cardiac
      tamponade. Forceful traction may result in uncoiling of the conductor, disruption
      of the insulation, or complete fracture, leaving an intravascular remnant that
      may embolize or be a source for thrombosis. Although fixation and abandonment of
      an inactive chronically implanted lead is frequently appropriate and is known to
      pose little long-term risk, the retained inactive lead may interact adversely
      with a new active lead and then increase the risk of venous thrombosis, serve as
      a potential nidus for infection, or produce spurious electrical sensing signals
      that may be sensed by the pulse generator. Absolute indications for lead removal
      are those in which there would be a life-threatening situation if the lead were
      to remain in situ. In the absence of an absolute indication, the decision to
      proceed with extraction must be made by weighing the potential for serious
      morbidity or mortality against risks of the extraction technique. Techniques for
      lead removal include traction and open cardiotomy operations. When a portion of
      the lead is intravascular, forceps, snares, baskets, countertraction, or lead
      transection devices may be used to retrieve the fragment.

PMID- 2000757
TI  - Myocardial imaging with Tc-99m teboroxime: technique and initial results.
AB  - This study examined the results of Tc-99m teboroxime imaging in 22 patients aged
      59 +/- 9 years and compared the results with those of thallium-201. The exercise
      and rest teboroxime studies were obtained within 3 hours of each other using a
      dose of 15 mCi/study. Because of the very short wash-out half-life of teboroxime,
      imaging was begun within 1 to 2 minutes after injection. Both SPECT and planar
      images were obtained; the SPECT protocol was modified by changing the number of
      frames, the time per frame, or the filters used for reconstruction of images. The
      planar images were obtained in the supine or upright position. Shorter
      acquisition time for SPECT (10 sec/frame) and the use of a Butterworth filter
      with a frequency cutoff of 0.3 cycle/cm and a power of 10 yielded best image
      quality. There was a close agreement with thallium results in identifying an
      abnormal or normal perfusion pattern in 89% of vascular territories. The scans
      were abnormal by both techniques in 12 patients, normal in nine patients, and
      discordant in only one patient. Thus Tc-99m teboroxime myocardial imaging is
      feasible at rest and during exercise using either SPECT or planar imaging.
      Shorter acquisition time and appropriate filtering for SPECT imaging and the
      upright position in planar imaging improve image quality and are convenient for
      the patient.

PMID- 2000758
TI  - A rare complication of percutaneous transluminal coronary angioplasty--left main
      disease.

PMID- 2000759
TI  - Case of steel versus steal: coil embolization of congenital coronary
      arteriovenous fistula.

PMID- 2000760
TI  - Transesophageal continuous-wave Doppler to evaluate mitral prosthetic stenosis.

PMID- 2000761
TI  - Delayed rupture of right coronary artery after directional atherectomy for bail
      out.

PMID- 2000762
TI  - Balloon occlusion of the ascending aorta for angiographic visualization of the
      coronary arteries in neonates with transposition of the great arteries.

PMID- 2000763
TI  - Transesophageal echocardiographic guidance for balloon catheter occlusion of
      patent foramen ovale complicating right ventricular infarction.

PMID- 2000764
TI  - Acute fulminant myocarditis: long-term follow-up after circulatory support with
      left ventricular assist device.

PMID- 2000765
TI  - Vagolytic therapy in acute cardiac tamponade associated with aortic dissection.

PMID- 2000766
TI  - Congenital acquired immunodeficiency syndrome presenting as cor pulmonale in a 10
      year-old girl.

PMID- 2000767
TI  - Transthoracic and transesophageal echocardiographic diagnosis of myxomas in the
      four cardiac cavities.

PMID- 2000768
TI  - Ruptured aortic dissection into the left atrium: a rare cause of congestive heart
      failure.

PMID- 2000769
TI  - Hearts too good to die: ventricular fibrillation due to small infarctions or
      ischemia.

PMID- 2000770
TI  - Uncomplicated vaginal delivery 14 months after cardiac transplantation.

PMID- 2000771
TI  - Myocarditis--continuing clinical and pathologic confusion.

PMID- 2000772
TI  - Risk factors for coronary artery disease: taking the family history.

PMID- 2000773
TI  - Epidemiology of heart failure.
AB  - Analysis of 34 years of follow-up of Framingham Study data provides clinically
      relevant insights into the prevalence, incidence, secular trends, prognosis, and
      modifiable risk factors for the occurrence of heart failure in a general
      population sample. Heart failure was found to be highly prevalent, affecting
      about 1% of persons in their 50s and rising progressively with age to afflict 10%
      of persons in their 80s. The annual incidence also increased with age, from about
      0.2% in persons 45 to 54 years, to 4.0% in men 85 to 94 years, with the incidence
      approximately doubling with each decade of age. Women lagged slightly behind men
      in incidence at all ages. Male predominance was because of a higher rate of
      coronary heart disease, which confers a fourfold increased risk of heart failure.
      Heart failure, once manifest, was highly lethal, with 37% of men and 33% of women
      dying within 2 years of diagnosis. The 6-year mortality rate was 82% for men and
      67% for women, which corresponded to a death rate fourfold to eightfold greater
      than that of the general population of the same age. Sudden death was a common
      mode of exitus and accounted for 28% of the cardiovascular deaths in men and 14%
      in women with heart failure. Hypertension and coronary disease were the
      predominant causes for heart failure and accounted for more than 80% of all
      clinical events. Factors reflecting deteriorating cardiac function were
      associated with a substantial increase in risk of overt heart failure. These
      include low vital capacity, sinus tachycardia, and ECG evidence of left
      ventricular hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2000774
TI  - Mechanisms of vasoconstriction.
AB  - The contractility of vascular smooth muscle cells is controlled in a complex
      manner by both extracellular and intracellular messages. The vascular endothelium
      does not simply act as a physical barrier between the blood and smooth muscle
      cells, it integrates intravascular signals and controls the contractility of
      underlying smooth muscle cells by way of release of paracrine factors with
      contracting or relaxing properties. Vasoconstrictors trigger a cascade of
      interacting intracellular signals that concur in initiating and maintaining
      contractions. Each step of these signalling pathways is a possible logical site
      for potential therapeutic interventions.

PMID- 2000775
TI  - Future directions in vasodilator therapy for heart failure.
AB  - Vasodilator therapy has become a major pharmacologic approach for improving left
      ventricular function, and consequently, vasodilator drugs are being used
      increasingly in the treatment of heart failure. Ideally, vasodilator drugs used
      in the long-term management of heart failure should show clearly defined
      pharmacodynamic effects. These include reduced impedance to left ventricular
      ejection, increased venous capacitance, increased left ventricular ejection
      fraction and reduced heart size, absence of neurohormonal stimulation, and slowed
      progression of left ventricular dysfunction. The mechanisms of action and sites
      of activity of the various vasodilator drugs currently available vary
      considerably, and none as yet has proved ideal for the treatment of heart failure
      or hypertension. The complexity surrounding the multiple vasoconstrictor
      mechanisms involved in heart failure has led to a rationale for combined
      vasodilator therapy and certain combinations are discussed. From a therapeutic
      standpoint, the development of drugs with multiple mechanisms of action is
      particularly attractive. Flosequinan is a new vasodilator agent whose cellular
      mechanism of action remains uncertain. Flosequinan has the advantage of being
      able to relax both arterial and venous beds and as such may be particularly
      beneficial in the treatment of heart failure.

PMID- 2000776
TI  - Pharmacology of flosequinan.
AB  - Flosequinan is a novel quinolone with cardiovascular activity that is likely to
      be of value in the treatment of both heart failure and hypertension. Data
      generated from animal studies indicate that flosequinan produces dilatation in
      both veins and arteries, with little associated reflex tachycardia. The compound
      shows some positive inotropic effects, but the potency is very species dependent.
      The mode of action of flosequinan seems to involve intracellular calcium
      handling.

PMID- 2000777
TI  - Clinical efficacy of flosequinan in heart failure.
AB  - The effects of the new arterial and venous vasodilator flosequinan have been
      evaluated in a variety of ways in different groups of patients with chronic heart
      failure. Flosequinan improved the central hemodynamic effects of heart failure in
      one group, with benefits still apparent up to 24 hours after a single oral dose.
      In another group it also improved calf blood flow and, therefore, blood flow to
      skeletal muscle. Also, using a number of different tests, it improved the
      exercise performance of the patients. In a further group the improvement in
      exercise tolerance produced was similar to that of captopril. Flosequinan has the
      necessary properties of a drug that is likely to be of benefit in the treatment
      of patients with chronic heart failure.

PMID- 2000778
TI  - Pharmacy issues to be highlighted in 102nd Congress.

PMID- 2000779
TI  - Specialization in pharmacy.

PMID- 2000780
TI  - Patient rounds at NIH.

PMID- 2000781
TI  - Ibuprofen: a monograph.
AB  - Nonprescription ibuprofen is useful for managing minor aches and pains, reducing
      fever, and relieving symptoms of dysmenorrhea. For these indications, ibuprofen's
      effectiveness has been judged to be equal or superior to other available
      nonprescription analgesics. Ibuprofen is not recommended for self-treatment in
      children less than 12 years old.

PMID- 2000782
TI  - Marketing to the mature population, Part 1: Evaluating the attractiveness of the
      mature population.
AB  - The mature population represents a major market force for the 1990s and the 21st
      century. Individuals age 65 and older make up a sizable percentage of the
      population and spend billions of dollars on health-related products and services.
      Despite the size and apparent attractiveness of this market, it may not be an
      easy one to penetrate. Pharmacists must recognize the vast differences within
      this group in terms of what its members want and expect from pharmacies. Only by
      understanding the unique attributes of the specific subgroups can pharmacists
      develop an effective marketing plan to serve their needs profitably. Specific
      marketing techniques for attracting segments of the mature population are
      described in Part 2.

PMID- 2000783
TI  - Diet drug safe and effective.

PMID- 2000784
TI  - Profits in orphan drugs.

PMID- 2000785
TI  - Early beneficial effect of streptokinase on left ventricular function in acute
      myocardial infarction.
AB  - The effect of intravenous streptokinase therapy on the time course of functional
      recovery was investigated in a controlled study of 64 patients randomized within
      3 hours after the onset of acute myocardial infarction (AMI). Contrast
      ventriculography was performed 1 to 4 days after AMI and repeated 5 weeks later.
      Wall motion was analyzed by the centerline method in the central infarct,
      peripheral infarct and noninfarct regions. In patients with ventriculographic
      data at the early catheterization, streptokinase-treated patients had less severe
      hypokinesia in the central infarct region than control patients (-2.9 +/- 0.9 [n
      = 29] vs -3.4 +/- 0.7 standard deviations below normal [n = 21], p less than
      0.05). The benefit of streptokinase was more marked in the peripheral infarct
      region (-1.5 +/- 0.7 vs -2.1 +/- 0.6, p less than 0.001). As a result, the
      ejection fraction was slightly higher in treated versus control groups (46 +/- 10
      vs 43 +/- 7%, respectively; difference not significant). At 5 weeks, function in
      the streptokinase and control groups had diverged further because of continued
      improvement in the streptokinase-treated patients. This study shows that
      streptokinase benefits left ventricular (LV) function by 1 to 4 days after AMI,
      earlier than previously reported. The benefit was not limited to the peripheral
      infarct region, where ischemia might have been less severe, but was also seen in
      the central infarct region. The implication is that thrombolytic therapy can
      improve LV function during the period of myocardial stunning, while myocardial
      function is still recovering.

PMID- 2000786
TI  - Effects of nisoldipine on myocardial ischemia during exercise and during daily
      activity.
AB  - The antiischemic properties of nisoldipine, a dihydropyridine calcium antagonist,
      were assessed in a multicenter, double-blind, placebo-controlled trial by
      repeated exercise testing and 72-hour ambulatory electrocardiographic monitoring
      in 82 patients with coronary artery disease. Patients with positive treadmill
      stress test results and greater than or equal to 2 ischemic episodes per 24 hours
      were included in this study. Administration of all chronic antiischemic
      medications except beta blockers were discontinued. During the first week all
      patients received placebo twice daily. During the second and third weeks, 41
      patients received nisoldipine 10 mg and 41 patients received placebo twice daily.
      In the placebo group there were no changes in exercise parameters or in
      ambulatory electrocardiographic parameters. In the nisoldipine group, exercise
      duration increased from 403 to 448 seconds (p = 0.0035), time to 1 mm of ST
      depression increased from 224 to 298 seconds (p = 0.002), time to pain increased
      from 241 to 321 seconds (p = 0.01), and maximal ST depression was reduced from
      2.6 to 2.3 mm (p = 0.002). Among the ambulatory electrocardiographic parameters
      in the nisoldipine group, only the number of episodes was reduced, from 14.4 to
      11.6 (p = 0.0013) per patient. There was no significant reduction in total
      ischemic time (132 vs 120 minutes per patient). No significant side effects were
      observed. This is the largest clinical trial to date on the effects of
      nisoldipine on myocardial ischemia. The results indicate that nisoldipine was
      effective in improving all exercise parameters and only partially effective in
      suppressing ischemia during daily activity.

PMID- 2000787
TI  - Usefulness of blood lactate as a predictor of shock development in acute
      myocardial infarction.
AB  - Data were obtained and analyzed in 229 patients admitted to the coronary care
      unit from November 1988 through July 1989. The patients were classified into 2
      groups: patients without or with only mild left ventricular failure (Killip class
      I or II) during their hospital stay (group I), and patients who were in Killip
      class I or II on admission but developed cardiogenic shock during hospitalization
      (group II). Discriminant function analysis was performed using the following
      variables: patients' age, history of previous myocardial infarction, diabetes
      mellitus, blood lactate, urea, creatinine, creatine kinase, aspartate
      aminotransferase, lactate dehydrogenase concentrations, and chest x-ray
      cardiothoracic ratio. Variables that were found to significantly discriminate the
      2 groups of patients were age, previous infarction, x-ray cardiothoracic ratio,
      blood urea and lactate concentrations. The risk index was computed, and blood
      lactate was the variable with the greatest predictive power for shock
      development. The sensitivity, specificity and predictive value of the risk index,
      taking various cutoff points, were calculated. With a cutoff value of 1,
      sensitivity was 65%, specificity 91%, positive predictive value 36% and negative
      predictive value 97%. With a cutoff value of 2, sensitivity was 53%, specificity
      99%, positive predictive value 82% and negative predictive value 96%.

PMID- 2000788
TI  - Long-term follow-up of the first 56 patients treated with intracoronary self
      expanding stents (the Lausanne experience).
AB  - Fifty-six patients treated with the self-expanding intracoronary stent for acute
      occlusion during percutaneous transluminal coronary angioplasty (PTCA) or
      restenosis were followed for 24 to 43 months (mean 34). Successful deployment and
      positioning were achieved in 55 of 56 patients. Occlusion of the stent was
      documented in 8 patients, the earliest occurring 30 minutes and the latest 8
      months after implantation. Three of the occluded stents were recanalized by PTCA.
      Coronary artery bypass grafts (CABG) were required in 4 patients: 1 for
      symptomatic restenosis, 1 for left main stenosis adjacent to the stent and 2 for
      acute ischemia during the in-hospital stay (less than 7 days). Myocardial
      infarction occurred in the territory of the stented vessel in 8 patients. Seven
      patients died between 1 day and 19 months after implantation. Local bleeding
      complications occurred in 10 patients, with 5 requiring blood transfusion.
      Restenosis within the stent was angiographically documented in 5 patients (9%). A
      new lesion in the treated vessel was found in 10 patients, followed by
      implantation of a second stent in 5 and a third stent in 1 patient. Medical
      treatment was instituted in the remaining 4 patients. Forty-nine patients (88%)
      are alive. Twenty-nine patients (51%) remained asymptomatic, and 44 (78%) are in
      a better functional class than before the implantation. Eleven of 15 (79%) major
      complications (acute occlusions or deaths) occurred in patients who received a
      stent in the left anterior descending coronary artery. In conclusion,
      implantation of the self-expanding intracoronary stent appears to be a new
      therapeutic option for treating acute occlusion or restenosis after
      PTCA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2000789
TI  - Capabilities of supine exercise electrocardiography versus exercise radionuclide
      angiography in predicting coronary events.
AB  - The ability of supine exercise electrocardiography and exercise radionuclide
      angiography to predict time to subsequent cardiac events (cardiac death, nonfatal
      myocardial infarction or late coronary bypass grafting or angioplasty) were
      compared in 265 patients with normal resting electrocardiograms who were not
      taking digoxin. All patients had undergone coronary catheterization and were
      initially treated medically. Follow-up study was performed at a median of 51
      months. Separate logistic regression models, which had been previously developed
      to predict 3-vessel or left main coronary artery disease (CAD), were compared
      using a Cox regression analysis to predict time to a subsequent cardiac event.
      The exercise electrocardiography model, consisting of the magnitude of ST
      depression, exercise heart rate and patient gender, was a powerful predictor (chi
      square = 30.8, p less than 0.0001) of subsequent events. The exercise
      radionuclide angiography model, which included the exercise response of the
      pressure-volume ratio in addition to the exercise electrocardiography variables,
      had similar prognostic power (chi-square = 31.8, p less than 0.0001). In a
      separate analysis considering only cardiac death and nonfatal myocardial
      infarction, the exercise electrocardiography model remained a significant
      predictor of events (chi-square = 12.2, p less than 0.001). None of the
      radionuclide angiography variables added significantly to the prognostic power of
      the exercise electrocardiography model. Thus, in patients with a normal resting
      electrocardiogram who are not taking digoxin, the supine exercise
      electrocardiography model that predicts 3-vessel or left main CAD also predicts
      future cardiac events. Exercise radionuclide angiography does not provide any
      additional prognostic information in such patients.

PMID- 2000790
TI  - Cardiac Arrest in Seattle: Conventional Versus Amiodarone Drug Evaluation (the
      CASCADE study).
AB  - This randomized study evaluates survivors of out-of-hospital ventricular
      fibrillation (VF) not associated with a Q-wave acute myocardial infarction who
      are deemed to be at a high risk of recurrence of VF. It compares the outcome of
      treatment with empirically administered amiodarone with the outcome of treatment
      with other antiarrhythmic agents guided by electrophysiologic testing or Holter
      recording, or both. The goal of therapy guided by electrophysiologic testing is
      to suppress inducible ventricular tachycardia (VT) or VF. Holter recording is
      used as the primary means of adjusting therapy only if patients are noninducible
      at the baseline electrophysiologic study. Patients are stratified according to
      cardiac diagnosis, ejection fraction, and whether they had previously received an
      antiarrhythmic agent that failed to suppress their arrhythmias. The primary end
      point of the study is total cardiac mortality. The first patient was enrolled in
      a pilot study on April 26, 1984. By October 1988, 142 patients had been enrolled
      in the full study and, as of May 1990, 199 patients have been enrolled.
      Compliance with therapy has been good, with no patients lost to follow-up and 8%
      of patients, equal in both drug groups, crossing over to alternate therapy.
      Baseline clinical characteristics remain similar in amiodarone and conventional
      drug groups. Pulmonary toxicity with amiodarone is 7% at 1 year, with no patients
      dying of pulmonary toxicity. In the first 142 patients, the overall 1-year
      cardiac mortality was 19%, with a 17% arrhythmic mortality (either VF or presumed
      arrhythmic death).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2000791
TI  - Relation of cardiac output at rest and during exercise to age in essential
      hypertension.
AB  - It has been suggested that the decline of cardiac output with age is due to
      increased prevalence of disease, particularly occult coronary artery disease.
      Therefore, the relation of cardiac output (direct oxygen Fick method) to age was
      analyzed in 110 sixteen- to 64-year-old men with World Health Organization stage
      I or II essential hypertension at the time of the hemodynamic study, who were
      alive and free of cardiovascular complications 7 years later. At supine and
      seated rest, during upright bicycle exercise at 50 W and and at peak work load,
      cardiac output was inversely (p less than 0.01) related to age. These relations
      were independent of weight and mean intraarterial pressure. Stroke volume
      decreased with advancing age at supine rest, but not at rest and during exercise
      in the seated position. Heart rate was not affected by age in the supine
      position, but was slower in older patients during upright rest and at peak
      exercise. In conclusion, in patients with essential hypertension who remained
      free of cardiovascular complications for 7 years, cardiac output was
      independently and inversely related to age at various levels of activity. These
      findings suggest that occult cardiovascular disease does not explain the decline
      in cardiac output with age in patients with essential hypertension.

PMID- 2000792
TI  - Comparison of the effects of guanadrel sulfate and propranolol on blood pressure,
      functional capacity, serum lipoproteins and glucose in systemic hypertension.
AB  - In a controlled, double-blind, crossover study, the effects of guanadrel sulfate
      and propranolol on blood pressure (BP) and selected cardiopulmonary and metabolic
      variables were compared in 15 physically active and moderately hypertensive
      subjects. Guanadrel sulfate reduced systolic and diastolic BP at rest by -16 and 
      15 mm Hg, and at maximal exercise by -33 and -13 mm Hg, respectively (p less than
      0.005), without affecting submaximal oxygen consumption (VO2), maximal VO2,
      ventilatory threshold, forced vital capacity, forced expiratory volume in 1
      second, or fatigue, as assessed by perceived exertion. In contrast, propranolol
      significantly decreased diastolic BP at rest (-16 mm Hg) and systolic BP at
      maximal exercise (-44 mm Hg); however, it significantly decreased submaximal VO2
      (-3.9 ml.kg-1.min-1), maximal VO2 (-3.9 ml.kg-1.min-1), ventilatory threshold (
      0.3 liters.min-1), minute ventilation at submaximal exercise (-7.3 liters.min-1),
      forced expiratory volume in 1 second (-0.27 liters), and concomitantly increased
      the rating of perceived exertion at maximal exercise (1.9 U). Guanadrel sulfate
      was also associated with significant decreases in mean fasting plasma glucose and
      total serum cholesterol, whereas propranolol resulted in an increase in serum
      triglycerides (p less than 0.05). In contrast to propranolol, guanadrel sulfate
      appears to decrease BP without evoking negative metabolic consequences or
      impairing exercise tolerance.

PMID- 2000793
TI  - Abnormal baroreflex control of heart rate in decompensated congestive heart
      failure and reversal after compensation.
AB  - Congestive heart failure (CHF) causes impairment of baroreflex control of heart
      rate (HR). To determine if this derangement is reversible, the cardiac
      chronotropic control was assessed in 10 patients with class IV chronic CHF of
      various etiologies before and after compensation achieved by bed rest, salt
      restriction, diuretics and vasodilators. Mean time between the 2 studies was 15
      +/- 3 days. The management was modified 3 days before the second autonomic
      evaluation, so as to reestablish the same diet and pharmacologic conditions of
      the previous study. Compensation led to significant reduction in symptom-based
      class, body weight, and pulmonary and systemic congestion. Mean +/- standard
      error of the mean HR responses (beats/min) before and after compensation were,
      respectively: (1) to atropine (0.04 mg/kg): 10 +/- 2 and 27 +/- 2 (p less than
      0.01); (2) to handgrip (30% maximum capacity, 1 minute): 9 +/- 2 and 19 +/- 3 (p
      less than 0.005); (3) to headup tilt (5 minutes): 4 +/- 3 and 20 +/- 4 (p less
      than 0.005). Mean +/- standard error of the mean baroreflex sensitivity (ms/mm
      Hg) of RR responses to phenylephrine and amyl nitrate-induced changes in systolic
      pressure was, respectively, in each condition: phenylephrine, 0.9 +/- 0.2 and 8
      +/- 2.3 (p less than 0.05); amyl nitrate, 0.3 +/- 0.2 and 4.1 +/- 1.1 (p less
      than 0.05). A significant correlation between improvement in HR responses to
      atropine and tilt and changes in body weight was obtained. These findings show a
      reversible component of impaired baroreflex control of HR in severe CHF, possibly
      due to its congestive effects.

PMID- 2000794
TI  - Doppler echocardiographic study of porcine bioprosthetic heart valves in the
      aortic valve position in patients without evidence of cardiac dysfunction.
AB  - To study the natural history of the hemodynamic performance of bioprosthetic
      heart valves, Doppler echocardiograms were recorded in a group of clinically
      stable patients at 2 and 5 years after replacement of native aortic valves with
      bioprosthetic valves. Eighteen patients completed a 2-year and 26 patients a 5
      year follow-up examination. The effective orifice areas of identical models of
      bioprosthetic valves (Hancock II) were determined in vitro in a left-sided heart
      pulse duplicator system. In vivo Doppler-derived effective orifice areas were
      compared with the in vitro measurements for the same valve size. At both the 2-
      and 5-year follow-up examinations, the Doppler-derived effective orifice area was
      significantly less than the in vitro area (p less than 0.0001 at each interval).
      Ten of 16 valves evaluated serially decreased greater than 0.20 cm2 in the
      Doppler-derived effective orifice area between studies. The mean decrease in
      effective orifice area in valves evaluated serially was 0.25 +/- 0.29 cm2 (p less
      than 0.005). The peak transaortic gradient increased from 21 +/- 6 to 27 +/- 8 mm
      Hg (p less than 0.01). The mean transaortic gradient increased from 12 +/- 4 to
      15 +/- 7 mm Hg (p less than 0.05). It is concluded that serial Doppler
      echocardiographic studies demonstrate a deterioration in the hemodynamic
      performance of bioprosthetic valves over time in patients with no symptoms or
      signs of valvular dysfunction and that Doppler echocardiography may be useful for
      identifying subclinical bioprosthetic valvular dysfunction.

PMID- 2000795
TI  - Clinical and Doppler echocardiographic follow-up after percutaneous balloon
      valvuloplasty for aortic valve stenosis.
AB  - Percutaneous balloon valvuloplasty has been shown to increase the aortic orifice
      area and to improve clinical symptoms. However, there are only few data
      concerning long-term results after balloon valvuloplasty. In this study, 36
      patients (11 men, 25 women, mean age 75 +/- 8 years) were followed after balloon
      valvuloplasty for a period of up to 18 months by means of clinical parameters and
      repeated Doppler echocardiographic measurements after 1, 3, 6, 12 and 18 months.
      Invasive measurements revealed a decrease of the systolic peak gradient from 78
      +/- 24 to 38 +/- 13 mm Hg (p less than 0.001), and an increase in the aortic
      orifice area from 0.58 +/- 0.23 to 0.93 +/- 0.2 cm2 (p less than 0.001). The
      Doppler echocardiographic approach revealed that the maximal instantaneous
      gradient decreased from 96 +/- 26 to 67 +/- 22 mm Hg (p less than 0.001). The
      aortic orifice area increased from 0.49 +/- 0.16 to 0.73 +/- 0.21 cm2 (p less
      than 0.001). Three patients (8%) died in the hospital. After hospital discharge,
      16 patients (44%) died and 8 patients (22%) underwent successful aortic valve
      replacement after a mean follow-up of 8 +/- 6 months. Nine patients (25%) were
      alive after a follow-up period of 18 months. Seven of these (19%) remained
      clinically improved. During follow-up, the Doppler echocardiographic results
      revealed a continuous trend toward the preprocedural severity of the aortic valve
      stenosis. Progression of restenosis assessed by Doppler echocardiographic
      measurements was accelerated in the group of patients who subsequently died or
      underwent repeat balloon valvuloplasty or aortic valve replacement.

PMID- 2000796
TI  - Effect of heart rate on left ventricular diastolic transmitral flow velocity
      patterns assessed by Doppler echocardiography in normal subjects.
AB  - Although a number of factors, including age and ventricular loading, are known to
      influence the pattern of left ventricular (LV) filling as depicted by Doppler
      echocardiographic transmitral flow velocities, few and conflicting data are
      available regarding the influence of heart rate (HR). Therefore, 20 volunteers
      (mean age 30 years) were evaluated with pulsed-wave Doppler echocardiography,
      performed with the sample volume placed at the mitral anulus level in the apical
      4-chamber projection. Transmitral flow measurements comprised peak and integrated
      early passive (E) and late atrial (A) filling velocities and the slope of
      velocity decline from peak E filling. Measurements were recorded during baseline
      (sinus rhythm, mean 70 beats/min) and during transesophageal atrial pacing (mean
      88 beats/min). LV end-diastolic dimension, mean arterial pressure and PR interval
      (corrected for pacing-induced delay in interatrial conduction time) were
      unchanged during pacing versus baseline measurements. Peak and integrated E
      filling velocities averaged 0.59 +/- 0.09 m/s and 6 +/- 1 cm, respectively, at
      baseline and were not significantly greater at the higher HR. In contrast,
      baseline peak and integrated A velocities averaged 0.37 +/- 0.06 m/s and 2.3 +/-
      0.7 cm, respectively, but were significantly greater at the higher HR (0.5 +/-
      0.07 m/s and 3.2 +/- 1.1 cm, respectively [p less than 0.003 vs baseline for
      each]). Further analysis of a subgroup of 9 subjects for whom Doppler
      measurements were available at 3 HRs (sinus 70; pacing 80 and 90) yielded strong
      evidence for a linear relation between HR and peak A velocity (A = 0.008 HR -
      0.21, with p less than 0.0001 for significance of the linear trend).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 2000797
TI  - Effects of the immunosuppressant cyclosporine on the circulation of heart
      transplant recipients.
AB  - The effect of cyclosporine on the systemic circulation and on heart rate is
      unknown for heart transplant recipients. Thirty-four heart transplant recipients
      were studied by right-sided cardiac catheterization after endomyocardial biopsy.
      A direct linear relation was found between systemic and pulmonary vascular
      resistance and cyclosporine trough blood levels, which were negatively related to
      heart rate. The effect of cyclosporine on pulmonary vascular resistance, however,
      was not statistically significant by multivariate analysis when patient age was
      considered. In contrast, renal function appeared unrelated to systemic vascular
      resistance or heart rate. It appears that cyclosporine trough blood levels may
      have a direct effect on systemic vascular resistance as well as an unexplained
      negative chronotropic effect on heart rate.

PMID- 2000798
TI  - Effects of exercise training on cardiorespiratory function in men and women older
      than 60 years of age.
AB  - This study reports the physiologic effects of up to 14 months of aerobic exercise
      in 101 older (greater than 60 years) men and women. After an extensive baseline
      physiologic assessment (Time 1), in which aerobic capacity and blood lipids were
      measured, subjects were randomized to an aerobic exercise condition (cycle
      ergometry, 3 times per week for 1 hour), nonaerobic yoga (2 times per week for 1
      hour), or a waiting list nonexercise control group for 4 months, and then
      underwent a second (Time 2) assessment. At the completion of the second
      assessment, all remaining subjects completed 4 months of aerobic exercise and
      were reevaluated (Time 3). Subjects were given the option of participating in 6
      additional months of supervised aerobic exercise, and all available subjects
      completed a fourth assessment (Time 4) 14 months after their initial baseline
      evaluation. Results indicated that subjects generally exhibited a 10 to 15%
      improvement in peak oxygen consumption after 4 months of aerobic exercise
      training, and a 1 to 6% improvement in aerobic power with additional aerobic
      exercise training. On the other hand, subjects, especially men, continued to have
      improvements in submaximal exercise performance (i.e., anaerobic threshold). In
      addition, aerobic exercise was associated with an improved lipid profile;
      subjects participating in aerobic exercise for up to 14 months exhibited
      increased levels of high-density lipoprotein cholesterol. Maintenance of regular
      aerobic exercise for an extended time interval is associated with greater
      cardiovascular benefits among older adults than has been reported previously.

PMID- 2000799
TI  - A plea for two actions that need to be taken.

PMID- 2000800
TI  - Is ST elevation the only electrocardiographic response of the ischemic right
      ventricle?

PMID- 2000801
TI  - Differentiating anginal patients with coronary artery disease from those with
      normal coronary arteries using psychological measures.

PMID- 2000802
TI  - Lidocaine toxicity after subcutaneous infiltration in children undergoing cardiac
      catheterization.

PMID- 2000803
TI  - Indexing repetitive to single ventricular premature complexes: a new concept in
      acute drug testing.

PMID- 2000804
TI  - Accuracy of cross-sectional echocardiography in diagnosis of aortopulmonary
      window.

PMID- 2000805
TI  - Frequency of occurrence of residual ductal flow after surgical ligation by color
      flow mapping.

PMID- 2000806
TI  - Creation of pseudo narrowing during coronary angioplasty.

PMID- 2000807
TI  - Myocardial ischemia-induced transient anterior conduction delay.

PMID- 2000808
TI  - Endomyocardial biopsy finding in two patients with idiopathic dilated
      cardiomyopathy receiving long-term treatment with amiodarone.

PMID- 2000809
TI  - Intravascular ultrasound for diagnosis of aortic dissection.

PMID- 2000810
TI  - Mitral valve origin of pedunculated rhabdomyomas causing subaortic stenosis.

PMID- 2000811
TI  - Rapid preparation of pyrogen-free 2H2(18)O for human-nutrition studies.
AB  - We describe a compact ultrafiltration system for the removal of pyrogens and
      bacteria from water labeled with the stable isotopes of deuterium and oxygen-18.
      The ultrafiltration system is constructed from readily available commercial
      components and can achieve complete removal of pyrogens and bacteria from 1L
      contaminated water within 30 min. By use of our procedure, loss of the
      isotopically labeled water by retention in the filtration system was minimal. The
      purified water is suitable for both oral and intravenous administration to
      healthy human subjects participating in nutrition studies.

PMID- 2000812
TI  - Body composition in Pima Indians: validation of bioelectrical resistance.
AB  - To assess the validity of bioelectrical resistance (BR) in an obese population,
      body composition was determined by both hydrostatic weighing and by BR in 156
      Pima Indian volunteers representing a wide range of body weight (46.1-202.6 kg)
      and body composition (11-52% fat). A predictive equation was derived by use of
      data on height, BR, weight, age, and sex from 130 randomly selected volunteers
      and was applied to the remaining 26 volunteers. When compared with the
      manufacturer's software, the new equation increased correlations with hydrostatic
      weighing for predicting percent body fat and fat-free mass (FFM) from 0.70 to
      0.92 and 0.79 to 0.97, respectively. The manufacturer's software underestimated
      FFM by 5.3 +/- 8.6 kg (P less than 0.05) when compared with FFM derived from
      hydrostatic weighing whereas the new equation improved the accuracy to -0.1 +/-
      3.3 kg (NS). There were no significant effects of fluid intake (700 mL) or
      breakfast consumption on body composition as determined by BR. BR represents a
      simple and accurate way to assess body composition in Pima Indians with our newly
      derived equation.

PMID- 2000813
TI  - Sedentary daily expenditure: a base for estimating individual energy
      requirements.
AB  - As a base for estimating individual energy requirements, we propose using the
      energy expenditure of a sedentary day with regular meals and sleep at night.
      Ninety-five 24-h measurements of sedentary daily expenditure (SDE) by direct
      calorimetry on 37 men and women were analyzed, showing that fat-free mass
      combined with body mass index correlated highly with SDE (r2 = 0.92) with an SE
      of 5%. Weight and fat mass were better predictors for women and excellent
      predictors for men. We found that weight and height accurately predicted fat mass
      if suitable exponents were used in the expression wt/htx. Testing predictive
      equations with our own and other sets of data showed good agreement between
      estimated and observed SDEs. As a base for estimating individual energy
      requirements. SDE is more precise than basal metabolic rate and it can be
      predicted with useful accuracy from simple measures of weight and height.

PMID- 2000814
TI  - Energy cost of lactation, and energy balances of well-nourished Dutch lactating
      women: reappraisal of the extra energy requirements of lactation.
AB  - At 9 wk postpartum the difference in energy intake of 40 lactating (2440 +/- 430
      kcal/d) and 16 nonlactating women (1680 +/- 400 kcal/d) was 760 kcal/d but
      decreased to 550 kcal/d when adjusted for habitual intakes and body weight.
      Energy cost of lactation amounted to 650 kcal/d (breast-milk production, 745 +/-
      130 g/d). When compared with nonlactating counterparts, the lactating women
      mainly achieved energy balance by eating more. Sixteen of the 40 lactating women
      were also studied at 56 wk. Their cost of lactation at 5-13 wk was 630 kcal/d
      (breast-milk production, 720 +/- 124 g/d); these women met their energy cost of
      lactation by eating more (415 kcal/d); by tissue mobilization (35 kcal/d), and by
      reducing energy expenditure (180 kcal/d). The present study helps in the
      understanding of how well-nourished women with an adequate lactational
      performance may cope in everyday life with the energy stress of lactation, and
      suggests that current recommendations of energy needs during lactation are too
      high.

PMID- 2000815
TI  - Human plasma fatty acid variations and how they are related to dietary intake.
AB  - A study was conducted in 12 free-living subjects to determine quantitative and
      qualitative plasma phospholipid (PL), free fatty acid (FFA), triglyceride (TG),
      and cholesterol ester (CE) fatty acid (FA) variations over time (0.8, and 22 mo)
      and to correlate these FAs with dietary intake. Diet, reported by use of a food
      frequency questionnaire (FFQ), did not change over time. Most FA variations were
      quantitative, occurring in FFA and CE fractions. Correlations between diet and
      FAs occurred mostly in men for whom dietary percent fat energy was positively
      correlated with percent monounsaturated plasma TG FAs, and ethanol (g/d) was
      positively correlated with plasma CE 16:1 omega 7 (mumol/L). These findings
      indicate that quantitative variations exist in plasma FAs of a normal population,
      with no detectable alteration in diet; the FFQ may be used to reflect the
      qualitative status of plasma FA. Factors such as ethanol consumption and sex
      differences may influence FA metabolism.

PMID- 2000816
TI  - Postheparin lipolytic activity and plasma lipoprotein response to omega-3
      polyunsaturated fatty acids in patients with primary hypertriglyceridemia.
AB  - The hypotriglyceridemic action of omega-3 (n-3) fatty acids is attributed
      primarily to reduction in hepatic triglyceride synthesis and reduced secretion of
      very-low-density lipoproteins (VLDLs). However, increased catabolism of
      triglyceride-rich lipoproteins was reported and could be due to increased
      availability of peripheral lipoprotein lipase (LPL) or hepatic lipase (HL). In
      this study plasma lipoproteins and postheparin activities of LPL and HL were
      determined in 12 patients with primary hypertriglyceridemia before and during
      isocaloric substitution of omega-3 fatty acids (10 g/d) for 4 wk. Omega-3
      polyunsaturates resulted in 53% and 61% reductions in plasma triglyceride and
      VLDL-cholesterol concentrations, respectively (P less than 0.0001). However, low
      density-lipoprotein (LDL)-cholesterol concentrations increased by 26% (P less
      than 0.001). Activities of postheparin LPL and HL essentially remained the same.
      Thus, in patients with primary hypertriglyceridemia, reduction in plasma
      triglyceride concentrations and increase in LDL-cholesterol concentrations
      mediated by omega-3 polyunsaturates seem to occur without an increase in LPL or
      HL activities.

PMID- 2000817
TI  - Fat absorption in neonates: comparison of long-chain-fatty-acid and triglyceride
      compositions of formula, feces, and blood.
AB  - We studied malabsorption of fat in neonates who were fed either a lard-modified
      formula (n = 22, gestational age, 33.6 +/- 3.9 wk) or an unmodified formula (n =
      14, gestational age, 34.1 +/- 3.7 wk). In both groups fecal lipid consisted
      almost completely (greater than 90%) of free fatty acids, whose composition was
      highly correlated with the corresponding formula's fatty acid composition [r =
      0.96 (lard modified) and r = 0.99 (standard)]. Both groups had similar relative
      amounts and compositions of fecal cholesterol esters and triglycerides. Plasma
      and, to a lesser extent, erythrocyte membrane long-chain-fatty-acid compositions
      correlated with those of the corresponding formulas. We suggest that the
      extensive intestinal hydrolysis and limited absorption of dietary lipids is, at
      least partly, due to lipolysis in the colon. Appearance of triglycerides in the
      colon may be due to a rapid small-intestinal passage in relation to small
      intestinal lipolysis.

PMID- 2000818
TI  - Lack of effect of chronic administration of oral beta-carotene on serum
      cholesterol and triglyceride concentrations.
AB  - Previous studies suggest that chronic oral administration of retinol and other
      retinoids causes elevation of plasma triglyceride concentrations. The effects of
      chronic oral administration of beta-carotene, a carotenoid partially metabolized
      to retinol, on plasma lipid concentrations have not been well studied; therefore,
      we studied 61 subjects over 12 mo while they were enrolled in a skin-cancer
      prevention study in which patients were randomly assigned to receive either
      placebo (n = 30) or 50 mg beta-carotene/d orally (n = 31). At study entry and 1 y
      later, fasting blood samples were obtained for measurement of triglycerides,
      total cholesterol, HDL cholesterol, retinol, and beta-carotene. Retinol
      concentrations changed minimally in both groups; beta-carotene concentration
      increased an average of 12.1 +/- 47 nmol/L in the placebo group and 4279 +/- 657
      nmol/L in the active-treatment group. Both groups experienced similar small
      increases in triglyceride and total cholesterol concentrations and small
      decreases in HDL cholesterol. Daily oral administration of 50 mg beta-carotene/d
      did not affect plasma lipid concentrations.

PMID- 2000819
TI  - Milk- and soy-protein ingestion: acute effect on serum uric acid concentration.
AB  - Acute effect of the ingestion of 80 g each of casein, lactalbumin, and soybean
      isolate on serum and urinary uric acid concentrations was investigated in 10
      healthy subjects. Serum and urinary uric acid concentrations were measured before
      and after the ingestion of proteins. Serum uric acid decreased significantly 3 h
      after ingestion of lactalbumin and casein but increased after soybean
      consumption. Urate clearance was significantly increased after ingestion of each
      of the three proteins. Multivariate analysis of urate clearance during
      lactalbumin and casein loads showed that independent correlation was obtained for
      serum alanine and urea concentration. These results demonstrate that, in addition
      to their known uricosuric effect, milk proteins acutely decrease serum uric acid
      concentration. Analysis of the effects of lactalbumin and casein on urinary uric
      acid elimination suggests that the uricosuric effect of proteins is a
      multifactorial phenomenon.

PMID- 2000820
TI  - Plasma amino acid concentrations and amino acid ratios in normal adults and
      adults heterozygous for phenylketonuria ingesting a hamburger and milk shake
      meal.
AB  - Plasma amino acid concentrations were measured and selected amino acid ratios
      were calculated in 12 normal adults and 12 adults heterozygous for
      phenylketonuria (PKU) ingesting a hamburger and milk shake meal providing 1 g
      protein/kg body wt. Plasma concentrations of all amino acids increased
      significantly over baseline after meal ingestion in both groups, reaching the
      highest mean values 3-5 h after meal ingestion. Plasma phenylalanine
      concentrations were significantly higher in heterozygous than in normal subjects
      both before and at all times after meal ingestion. The absolute increase in
      plasma phenylalanine concentration over baseline and the area under the plasma
      phenylalanine concentration-time curve were approximately twice as large in
      heterozygous as in normal subjects. However, the molar ratio of the plasma
      phenylalanine concentration to the sum of the plasma concentrations of the other
      large neutral amino acids did not increase significantly over baseline, but
      rather decreased.

PMID- 2000821
TI  - Lactose maldigestion and milk intolerance in healthy Greek schoolchildren.
AB  - The prevalence of lactose maldigestion in Greek adults is 75% but the age at
      which the lactase activity starts declining is not known. The prevalences of
      lactose maldigestion and intolerance were investigated in 150 randomly selected
      Greek children 5-12 y old by using breath-hydrogen analysis after ingestion of
      lactose (2 g/kg body wt, maximum 50 g) or 0.240 L of milk. Prevalence of lactose
      maldigestion increased with age (y = -7.30 + 6.49x, r = 0.88, P = 0.004), being
      29.4% and 80.0% at ages 5 and 12 y, respectively. Before testing, the reported
      prevalences of milk-related symptoms by children with high and low lactose
      digestion capacity were 21.1% and 39.7% (chi 2 = 5.96, P = 0.015), respectively.
      However, the corresponding prevalences of lactose intolerance after ingestion of
      milk were 7.3% and 8.6% (chi 2 = 0.1, P = 0.72) and only three children had a
      delta H2 greater than or equal to 20 ppm postprandially. Although intestinal
      lactase activity declines before age 5 y and many Greek children report milk
      related symptoms, true malabsorption and intolerance of lactose after a glass of
      milk is rarely seen at this age.

PMID- 2000822
TI  - Interaction between colonic acetate and propionate in humans.
AB  - Animal studies suggest that propionate, derived from colonic carbohydrate
      fermentation, may be gluconeogenic and inhibit cholesterol synthesis in the
      liver. We therefore studied, in six healthy subjects, the effect of rectally
      infused solutions containing acetate alone (180 mmol), propionate alone (180
      mmol), or a mixture of acetate (180 mmol) and propionate (60 mmol). Relative to
      the control infusion of normal saline, acetate increased serum cholesterol,
      glucagon, and acetate concentrations and reduced free fatty acids (FFAs) within
      30 min. Propionate alone increased serum propionate, glucose, and glucagon with
      no effects on cholesterol and a delayed fall in FFAs. The addition of propionate
      to acetate resulted in no significant rise in serum cholesterol. These results
      are consistent with the hypothesis that colonic propionate is a gluconeogenic
      substrate in humans and inhibits the utilization of acetate for cholesterol
      synthesis.

PMID- 2000823
TI  - Beta-carotene's effects on serum lipoproteins and immunologic indices in humans.
AB  - Doses of beta-carotene for cancer-prevention trials have been chosen based on
      epidemiologic data. Mechanisms of the putative antineoplastic effects by beta
      carotene are unknown but may involve modulation of the immune system. We measured
      plasma carotenoid concentrations and selected immunologic indices at baseline and
      at 2 and 4 wk in 50 healthy humans (5 groups of 10 each) ingesting 0, 15, 45,
      180, or 300 mg beta-carotene/d for 1 mo in this randomized placebo-controlled,
      open-label, parallel study. Plasma beta-carotene concentrations were markedly
      increased by 2 wk and were correlated with dose. Beta-carotene concentrations
      plateaued between 2 and 4 wk except for the 300-mg group. Thus, we developed a
      dose-concentration curve to optimize beta-carotene-dose selection to achieve
      target plasma concentrations. We were unable to identify any effects of beta
      carotene ingestion on the immunologic indices studied, but modest increases in
      high-density-lipoprotein cholesterol were observed in all beta-carotene-treated
      groups.

PMID- 2000824
TI  - Vitamin B-12 from algae appears not to be bioavailable.
AB  - The effect of algae (nori and spirulina) and fermented plant foods on the
      hematological status of vitamin B-12-deficient children was evaluated. Although
      rising plasma vitamin B-12 concentrations in children consuming only plant foods
      (0.1-2.7 micrograms vitamin B-12/d) indicated that the vitamin B-12 was absorbed,
      elevated baseline values of mean corpuscular volume (MCV) further deteriorated.
      In contrast, MCV improved in children receiving fish containing 0.15-0.5
      microgram vitamin B-12/d or a vitamin B-12 supplement. Further studies on the
      specificity of current vitamin B-12 assays are warranted. It seems unjustified to
      advocate algae and other plant foods as a safe source of vitamin B-12 because its
      bioavailability is questionable.

PMID- 2000825
TI  - Extremely low serum pyridoxal 5'-phosphate in children with familial
      hypophosphatemic rickets.
AB  - The apparent vitamin B-6 status of 31 children with familial hypophosphatemic
      rickets (FHR) was determined. All children had alkaline phosphatase activity that
      was high-normal to elevated for their ages. A sensitive assay for pyridoxal 5'
      phosphate (PLP) indicated that 15 of the 31 children had an undetectable (less
      than 0.2 nmol/L) concentration of the vitamer--the lowest values yet reported in
      human serum. The 16 remaining children had concentrations of the vitamer so low
      that they indicated a potential severe vitamin B-6 deficiency. However, none of
      the children had ever presented with any of the classical vitamin B-6-deficiency
      symptoms. Treatment of three additional FHR children with 100 mg pyridoxine.HCl/d
      resulted in a moderate and transient elevation of their serum PLP concentrations,
      a dramatic elevation of their erythrocyte PLP concentrations, and no improvement
      in clinical condition. Serum or plasma PLP concentrations are an inappropriate
      index for determining vitamin B-6 status in people with FHR and perhaps in others
      with elevated alkaline phosphatase activity.

PMID- 2000826
TI  - Can vitamin E protect humans against the pathological effects of ozone in smog?
AB  - Ozone reacts with polyunsaturated fatty acids (PUFAs) in vitro to form free
      radicals, and vitamin E slows or prevents this reaction. Consistent with this,
      dietary vitamin E significantly protects animals against the deleterious effects
      of ozone and the absence of vitamin E potentiates damage by ozone. Thus, chemical
      and animal studies as well as the opposite effects of ozone and vitamin E on the
      immune system suggest the hypothesis that vitamin E can protect humans against
      the harmful effects of chronic exposures to ozone. However, because most humans
      are not vitamin E deficient, the more relevant question is whether amounts of
      vitamin E above the minimum of dietary requirement provide increased protection.
      The need for and design of further studies to answer this question are discussed.

PMID- 2000827
TI  - Plasma tocopherol concentrations in response to supplemental vitamin E.
AB  - Normal healthy volunteers were studied after various doses of dl-alpha-tocopherol
      were ingested on different schedules. Administration of 440, 880, or 1320 mg
      (400, 800, or 1200 IU) of dl-alpha-tocopherol as a single dose resulted in
      elevation of plasma alpha-tocopherol concentrations that peaked at 12-24 h.
      Chronic administration of dl-alpha-tocopherol (440, 880, or 1320 mg/d for 28 d)
      resulted in a steady state that occurred by days 4-5 of supplementation.
      Discontinuation of the treatment after day 28 was associated with a decline of
      plasma alpha-tocopherol, which returned to the pretreatment concentrations
      between 12 and 20 d. The plasma elevation of alpha-tocopherol was affected by
      dietary fat intake. Individuals consuming a high-fat diet showed significantly
      greater plasma alpha-tocopherol concentrations as compared with those fed a low
      fat diet. The results of this study indicate that plasma kinetics of alpha
      tocopherol are similar when supplements of 440, 880, or 1320 mg dl-alpha
      tocopherol are given to normal, healthy individuals.

PMID- 2000828
TI  - Vitamin K in colostrum and mature human milk over the lactation period--a cross
      sectional study.
AB  - Vitamin K was quantitated in the milk of four groups of 15 mothers from 1 d to 6
      mo postpartum in a cross-sectional study. Concentrations were 7.52 +/- 5.90 and
      6.36 +/- 5.32 nmol/L (3.39 +/- 2.66 and 2.87 +/- 2.40 micrograms/L) in colostrum
      and mature milk, respectively. Differences between colostrum and mature milk or
      among samples of mature milk collected at 1, 3, and 6 mo were not statistically
      significant. Because of significantly increased volumes of milk over the
      lactation period, approximately twice as much vitamin K was delivered in mature
      milk as in colostrum. Within normal ranges, concentrations of vitamin K in milk
      were not predicted by dietary intake of vegetables or fat. Vitamin K was
      correlated with fat in colostrum and was localized in the lipid core of the milk
      fat globule but was not associated with membranes. Vitamin K in human milk is
      insufficient to meet recommended intakes for infants aged less than 6 mo.
      Population and clinical studies are needed to assess the vitamin K status of
      exclusively breast-fed infants and to evaluate current recommendations.

PMID- 2000829
TI  - Relative bioavailability of deuterium-labeled monoglutamyl and hexaglutamyl
      folates in human subjects.
AB  - The bioavailability of orally administered mono- and polyglutamyl folates was
      examined in humans by using stable-isotope methods. [3',5'-2H2]Folic acid (d2-FA)
      and [3',5'-2H2]pteroylhexaglutamate (d2-PteGlu6) were prepared for oral
      administration and (glu-2H4)folic acid (d4-FA) was prepared for intravenous (iv)
      injection. In two trials, adult males (n = 7) on a folate saturation regimen (2
      mg/d) were given a single 677-nmol oral dose of either d2-FA or d2-PteGlu6 in
      apple juice along with an iv injection of 502 nmol d4-FA as a control. Urine was
      collected for 48 h and the isotope labeling of urinary folates determined by mass
      spectrometry. The excretion ratio of urinary folates (% of d2-folate dose/% of d4
      folate dose) resulting from oral d2-FA and iv d4-FA was 1.45 +/- 0.10 (mean +/-
      SEM) whereas the ratio for oral d2-PteGlu6 and iv d4-FA was 0.67 +/- 0.04. These
      results indicate that the d2-PteGlu6 is available to humans as a source of folate
      although its bioavailability is substantially less than that of d2-FA under these
      conditions.

PMID- 2000830
TI  - Soybean phytate content: effect on calcium absorption.
AB  - Absorption of calcium from soybeans with low and high phytate contents,
      intrinsically labeled with 45Ca, was measured in 16 normal women and compared in
      15 of these same subjects with absorption of calcium from labeled milk. The
      average test load of calcium for all three sources was 2.45 mmol. Fractional
      calcium absorption (+/- SD) from the high-phytate soybeans averaged 0.310 +/-
      0.070; from the low phytate soybeans, 0.414 +/- 0.074; and from milk, 0.377 +/-
      0.056. The mean difference (+/- SEM) in fractional calcium absorption for the two
      phytate levels was 0.104 +/- 0.014 (P less than 0.001).

PMID- 2000831
TI  - Selenium distribution in blood fractions of New Zealand women taking organic or
      inorganic selenium.
AB  - Three groups of 11 New Zealand women each received, for 32 wk, yeast tablets with
      no added selenium (placebo) or 200 micrograms Se/d in tablets either as selenate
      or as selenium-enriched yeast (SeMet) in a double-blind selenium trial. Plasma
      and erythrocyte (RBC) samples were collected bimonthly. Gel filtration of plasma
      from women taking SeMet revealed two major selenium-containing peaks with most of
      the selenium in the second peak. In contrast, the first peak contained most of
      the selenium in plasma from women taking selenate. Chromatography of RBC lysates
      indicated that the majority of the selenium was with hemoglobin (Hb) in women
      taking SeMet but was about equally distributed between glutathione peroxidase
      (GSH-Px) and Hb in women taking selenate. The percentage of selenium associated
      with GSH-Px was found to be greater in RBCs and plasma of women taking selenate
      than of those taking SeMet.

PMID- 2000832
TI  - Homeostatic regulation of zinc absorption and endogenous losses in zinc-deprived
      men.
AB  - The mechanisms involved in the homeostatic regulation of zinc were studied in
      five male subjects by using stable 70Zn as a marker. When dietary zinc was
      reduced from 85 to 12 mumol/d, adaptation was achieved by a mean (+/- SEM)
      reduction in urine zinc of 48 +/- 7% and in fecal zinc of 46 +/- 12% over 25 d in
      four subjects. The latter was caused by an increase in the efficiency of zinc
      absorption from 38 +/- 3% to 93 +/- 1% after 15 d of zinic deprivation and by a
      reduction in intestinal endogenous losses of zinc. In a fifth subject, who had
      some evidence of a resolving alcohol-induced hepatitis, urine and fecal zinc were
      reduced by 64% and 41%, respectively, in 15 d and zinc absorption increased from
      46% to 93%. More information on adaptive responses is needed to enable current
      dietary recommendations to be reconsidered.

PMID- 2000833
TI  - Isotonic high-sodium oral rehydration solution for increasing sodium absorption
      in patients with short-bowel syndrome.
AB  - We compared the effect of a standard oral rehydration solution and a high-sodium
      polymeric-glucose solution on sodium absorption in short-bowel syndrome. Six
      patients with high jejunostomy were tested in a random order with the standard
      solution or a solution containing maltodextrins (18 g Glucidex 12/L) enriched
      with 2.5 g NaCl/L. Solutions were administered via a nasogastric tube at a rate
      of 2 mL/min. Jejunal effluent was collected during an 8-h period. The net 8-h
      fluid absorption was not significantly different in the two periods. Glucose
      absorption was greater than 90% of the administered amount for both solutions.
      Net sodium absorption was greater for the maltodextrin solution than for the
      standard solution (56 +/- 12 vs 24 +/- 20 mmol, P less than 0.05). We conclude
      that replacement of glucose with maltodextrins and addition of sodium in the
      standard oral rehydration solution results in improved sodium absorption in short
      bowel syndrome.

PMID- 2000834
TI  - Nutritional supplementation and the development of linear enamel hypoplasias in
      children from Tezonteopan, Mexico.
AB  - The purpose of this study was to compare the effect of nutritional intake during
      tooth-crown formation on the subsequent development of linear enamel hypoplasias
      (LEHs) in Mexican nonsupplemented (control) adolescents (n = 42) and adolescents
      who had received daily nutritional supplements since birth (n = 42). The
      proportion of individuals with LEHs was nearly two-fold greater (74.4%; 95% CI
      64.7-84.1%) in the control than in the supplemented group (39.5%; 95% CI 28.6
      50.4%; chi 2 = 9.44; P = 0.001). Although the estimated peak age at formation,
      approximately 2-2.5 y, is similar in both groups, the proportion of early (before
      1.5 y) and late (after 3.0 y) LEHs was greater in the control group. LEH was also
      more common in females and was associated with an increase in illness days and a
      decrease in growth velocity. Results of this study suggest that mild to moderate
      undernutrition during enamel formation is causally linked to the formation of
      LEHs.

PMID- 2000835
TI  - Nonabsorbable marker and single, random stool samples used for measuring
      intestinal absorption of macronutrients in infants and children.
AB  - To measure intestinal absorption by using a single, random stool sample,
      polyethylene glycol (PEG), 1 g/d, and a constant diet were given to healthy
      infants, with a constant PEG-to-macronutrient ratio. After 10 d equilibration,
      apparent intestinal absorption of macronutrients was estimated from a standard 3
      d metabolic balance and compared with that estimated by using the ratio of PEG to
      macronutrients in a single random sample of feces. Correlation coefficients for
      this comparison were 0.649, 0.715, and 0.924 for nitrogen, carbohydrate, and fat,
      respectively. Additionally, apparent intestinal absorptions estimated from two
      separate consecutive 3-d metabolic-balance studies were compared, showing
      correlation coefficients of 0.106, 0.653, and 0.463 for nitrogen, carbohydrate,
      and fat, respectively. The random sample-marker technique appears to be
      acceptable for measuring apparent absorption of macronutrients and is at least as
      accurate as a standard 3-d metabolic-balance study.

PMID- 2000836
TI  - Looking for a few good generalized body-fat equations.

PMID- 2000837
TI  - Energy expenditure and everyday eating behavior in healthy young women.

PMID- 2000838
TI  - Vegetable and fruit consumption in relation to prostate cancer risk in Hawaii: a
      reevaluation of the effect of dietary beta-carotene.
AB  - This is a further analysis of a case-control study of 452 prostate cancer cases
      and 899 population controls that was conducted in 1970-1983 among the multiethnic
      population of Hawaii. Because a previous analysis had shown a positive
      association with intake of beta-carotene, a nutrient presently being tested for
      chemoprevention, the authors reexamined the data for consistency among the main
      food sources of beta-carotene. Vegetables and fruits containing other
      phytochemicals suspected to be cancer inhibitors were also examined. With the
      exception of papaya, which was positively associated with risk among men aged 70
      years and older, consumption of other yellow-orange fruits and vegetables,
      tomatoes, dark green vegetables, and cruciferous vegetables was not associated
      with prostate cancer risk. These results suggest that: 1) the positive
      association with beta-carotene intake among older men that the authors previously
      reported was essentially due to the greater papaya consumption of cases compared
      with controls; and 2) intake of beta-carotene, lycopene, lutein, indoles,
      phenols, or other phytochemicals is not associated with prostate cancer risk.

PMID- 2000839
TI  - Lung cancer in mild steel welders.
AB  - To investigate lung cancer risk, the authors conducted a historical cohort
      mortality study of 4,459 mild steel welders who had been employed at three
      midwestern plants which manufactured heavy equipment. Follow-up began in the mid
      1950s and extended through 1988. All welders had at least 2 years welding
      experience (average duration, 8.5 years). This cohort had no occupational
      exposure to asbestos or stainless steel fumes (containing nickel and chromium),
      two potential confounders in previous welders studies. A comparison population of
      4,286 nonwelders, all with at least 2 years employment at the same plants, was
      also studied. Nonwelders had never been welders and were allowed to have no more
      than 90 days employment as a painter, foundryman, or machinist. Sampling data
      collected from 1974-1987 indicated that welders were exposed to 6-7 mg/m3 of
      total particulate and 3-4 mg/m3 of iron oxide, while nonwelders had negligible
      exposures to welding fumes. When compared with the United States population, both
      welders and nonwelders had elevated rates for lung cancer (standardized mortality
      ratios (SMRs): welders, SMR = 1.07; nonwelders, SMR = 1.17), but neither SMR was
      significantly elevated. Limited smoking data based on a 1985 survey indicated
      that both welders and nonwelders smoked more than the United States population,
      possibly accounting for part of their elevated lung cancer rates. There was no
      trend of increased risk for welders with increased duration of exposure. The only
      other cause of death significantly elevated was emphysema among welders.
      Nonmalignant respiratory disease was not elevated for welders (SMR = 0.96). When
      welders were compared with nonwelders directly for lung cancer, the rate ratio
      was 0.90.

PMID- 2000840
TI  - Bladder cancer in a low risk population: results from the Adventist Health Study.
AB  - A cohort study of bladder cancer was conducted in a population of California
      Seventh-day Adventists. Most Seventh-day Adventists use neither tobacco nor
      alcohol yet experience a large degree of variation in dietary habits. Therefore,
      diet and other lifestyle habits were evaluated in this unique population. In
      1976, 34,198 non-Hispanic white Seventh-day Adventists in California completed a
      detailed lifestyle questionnaire which included a 51-item food frequency section.
      This cohort was then followed until the end of 1982 during which time all newly
      diagnosed malignancies were detected. In order to evaluate the relation between
      several variables hypothesized to be associated with altered bladder cancer risk,
      age-, sex-, and smoking-adjusted relative risks (incidence rate ratios) were
      calculated using the method of Mantel-Haenszel adopted for person-time data.
      Multivariate analyses were conducted using the Cox Proportional Hazards
      Regression model. Between the return of the questionnaire and the end of follow
      up, there were 52 histologically confirmed bladder cancers detected in the
      cohort. Increasing age, male gender, and a history of cigarette smoking were all
      significantly associated with increased bladder cancer risk. In addition,
      residence in a rural area was associated with significantly increased risk
      (relative risk (RR) = 1.80) as was high consumption of meat, poultry, and fish
      (RR = 2.57).

PMID- 2000841
TI  - Recall (report) bias and reliability in the retrospective assessment of melanoma
      risk.
AB  - In a case-control study nested in the Nurses' Health Study cohort, the authors
      assessed recall bias in the ascertainment of two risk factors for melanoma: hair
      color and ability to tan. Participants reported on these risk factors in a 1982
      questionnaire and in a subsequent case-control questionnaire or telephone
      interview. The test-retest reliability among controls was high for both questions
      (Spearman's r = 0.76). Among women diagnosed with melanoma after the first
      questionnaire and before the second, there was a substantial shift toward
      reporting a reduced ability to tan when participants were questioned after the
      diagnosis of melanoma (p = 0.035). No shift was noted for the hair color question
      (p = 0.8). The authors conclude that recall bias was observed among female nurses
      with cutaneous melanoma in the assessment of tanning ability, a major risk factor
      for melanoma.

PMID- 2000842
TI  - Case-control studies of environmental influences in diseases with genetic
      determinants, with an application to Alzheimer's disease.
AB  - Many diseases have both genetic and environmental determinants. Some require
      both, and the disease phenotype then appears only when a vulnerable genotype is
      expressed after interaction with environmental factors. The detection of such
      environmental factors has received little prior consideration in diseases with
      genetic causes. In particular, case-control studies of such diseases may compare
      exposures among cases, who have the susceptible genotype, and controls who mostly
      lack it. The authors explored the likely results of such studies, using the
      example of Alzheimer's disease as an illness where environmental factors may
      interact with a necessary susceptible genotype to accelerate disease expression.
      They found that case-control studies of environmental factors in complex genetic
      diseases will usually produce an odds ratio that differs little from the relative
      risk among susceptible individuals. In rare situations, however, the discrepancy
      may be gross. The statistical power of such studies also agrees well with
      familiar published estimates, suggesting that little power is lost even though
      the controls are mostly not susceptible. Power may be increased, however, in
      studies of common illnesses with genetic determinants when the case-control
      method is applied among discordant monozygotic twins.

PMID- 2000843
TI  - Body fat distribution in relation to physical activity and smoking habits in 38
      year-old European men. The European Fat Distribution Study.
AB  - The authors studied 512 European men all born in 1950 from six different towns in
      the period October 1988 to May 1989. Anthropometric measurements were taken,
      including weight, height, and circumferences (waist, hip, thigh). Educational
      level, activity scores and information on smoking habits were obtained from a
      questionnaire. Higher educational level was associated with lower body mass
      index, waist/hip ratio, and waist/thigh ratio. The sports activity score was
      negatively related to waist/hip ratio (beta +/- standard error of the mean (SEM):
      -0.009 +/- 0.003) and waist/thigh ratio (-0.041 +/- 0.007), and this could be
      attributed to a negative relation with waist circumference and a positive
      relation to thigh circumference. Smoking habits were not related to body mass
      index but heavy smokers had larger waist circumferences (difference +/- SEM: 1.4
      +/- 0.5 cm) as well as higher waist/hip ratios (difference +/- SEM: 0.014 +/-
      0.005) and waist/thigh ratios (0.043 +/- 0.013) compared with men who never
      smoked. These associations between activity scores and smoking habits and fat
      distribution remained after adjustment for each other and for body mass index and
      educational level. The authors conclude that physical activity and smoking are
      independently related to indicators of fat distribution and may be potential
      confounders in the relations between fat distribution, risk factors, and disease.

PMID- 2000844
TI  - Reliability of long-term recall of participation in physical activity by middle
      aged men and women.
AB  - The reliability of long-term recall of physical activity participation was
      examined in 322 women and 129 men in a worksite health study conducted at the
      Liberty Corporation, Greenville, South Carolina during 1976-1987. Leisure time
      physical activity was assessed at baseline; and energy expenditure in total,
      light, moderate, and vigorous activities was calculated. The long-term recall of
      baseline activities was determined 1-10 years after the examination. The relation
      between actual baseline and recalled activity was positive and in most cases the
      coefficients were statistically significant at p less than 0.05. The correlations
      were modest, most in the range of 0.20 to 0.50. Percent agreement between
      baseline and recalled activity generally ranged from 60 to 75%. Multiple
      regression analyses suggested that recalled activity was a significant predictor
      of baseline activity, but recall interval and age were not important contributors
      to the regression model. R2 values for the model were 0.10 for light activity and
      0.26 for vigorous activity. Questionnaire assessment of long-term physical
      activity recall appeared to be reliable, length of recall interval up to 10 years
      was not an important factor, and recall of vigorous activity was more accurate
      than for less intensive activities.

PMID- 2000845
TI  - Backcalculation of the number with human immunodeficiency virus infection in the
      United States.
AB  - The method of backcalculation was applied to national surveillance data on the
      acquired immunodeficiency syndrome (AIDS) in order to estimate the cumulative
      number of adults with human immunodeficiency virus type 1 (HIV-1) infection as of
      January 1, 1985 and July 1, 1987. A "plausible range" of estimates was
      constructed which reflected both uncertainty about the AIDS incubation
      distribution and random variation from selection and fitting of flexible models
      of the HIV-1 infection curve. The authors estimated that, as of 1985, 411,000 to
      756,000 persons were infected. The infected population included 266,000 to
      492,000 homosexual men, 69,000 to 136,000 intravenous drug users, 24,000 to
      49,000 homosexual intravenous drug users, and 11,000 to 26,000 persons infected
      through heterosexual contact. The estimated prevalence of infection among persons
      aged 15-55 years was 0.31% in whites, 0.78% in Hispanics, and 0.81% in blacks. An
      estimated 32,000 to 66,000 women were infected. Compared with white women aged 15
      55 years, the prevalence of infection was 5.3-fold higher in Hispanic women and
      10.2-fold higher in black women. Plausible estimates for the total number
      infected by July 1987 ranged from 707,000 to 1,376,000, with the most likely
      estimate equal to 992,000. Backcalculation provides an assessment of the
      magnitude of the HIV-1 epidemic that is independent of estimates based on
      prevalence surveys in special populations. The estimates obtained from both
      methods are consistent and emphasize the need for vigorous programs to prevent
      the spread of HIV-1, especially in minority communities.

PMID- 2000846
TI  - Risk factors for carriage of meningococcus in the Los Angeles County men's jail
      system.
AB  - Ten cases of meningococcal meningitis in the Los Angeles County men's jail system
      in 1986 were the first known reported cases in this population. New cases have
      continued into 1990. Nineteen of 21 symptomatic cases identified by serogroup
      from the men's jail occurring through 1988 had serogroup C. The prevalence of
      meningococcal carriage and potential risk factors were studied in 1988 among 150
      men booked to enter the jail, 350 inmates being released, and 100 jail staff. The
      prevalence of meningococcal carriage among releases, bookings, and staff were
      25.4%, 18.7%, and 5.0%, respectively. Among releases, imprisonment longer than a
      threshold of 28 days increased carriage of serogroup C 10.0 times (95% confidence
      interval (CI) 4.6-21.6). Among bookings, household crowding increased serogroup C
      carriage 8.2 times (95% CI 1.5-45.3). Direct and passive smoking at home
      increased carriage of any serogroup 5.2 (95% CI 1.2-47.5) and 2.5 (95% CI 1.1
      5.8) times, respectively. Feasible potential interventions include banning
      smoking in the jail and immunization with quadrivalent meningococcal vaccine of
      booked men sentenced for one month or more.

PMID- 2000847
TI  - Age distribution of patients with medically-attended illnesses caused by
      sequential variants of influenza A/H1N1: comparison to age-specific infection
      rates, 1978-1989.
AB  - Since influenza A/H1N1 viruses reappeared during the 1977-1978 season, this
      subtype has contributed 27% of 6,609 documented influenza infections of persons
      with acute respiratory disease presenting to clinics serving as surveillance
      sites of the Influenza Research Center in Houston for the 12-year period ending
      June 1989. Wide differences in the distribution of H1N1 viruses occurred by age
      group: more than 50% of H1N1 infections were detected among persons aged 10-34
      years, compared with 28% for influenza A/H3N2 and 35% for influenza B. Over age
      35 years, the contribution of H1N1 viruses dropped to only 4%, compared with 20%
      and 16% for influenza A/H3N2 and influenza B, respectively. When birth dates of
      persons with positive cultures were examined, it was found that most of the H1N1
      positive persons were born after 1950. Concurrently, longitudinal studies of
      families and other adults under intensive surveillance for infection, including
      cultures of all respiratory illnesses and tests for serum antibody rise over the
      respiratory disease season, revealed appreciable infection rates for adults born
      before 1950. Furthermore, the annual peak of hospitalization of older persons
      with pneumonia and other acute respiratory illnesses was significantly correlated
      with the peak of H1N1 virus activity in 1978-1979, a year when H1N1 viruses were
      the only influenza viruses prevalent. These observations indicate that many
      persons infected with influenza A/H1N1 viruses that circulated from 1946 through
      1953 have immunity which has persisted for more than 25 years but this immunity
      is not complete. Reinfection that may result in serious illness in older
      vulnerable adults does occur but with lower frequency than with influenza A/H3N2
      infection. Currently prevalent H1N1 variants are antigenically different from
      those that circulated in the 1950s; however, older adults readily acquire
      immunity to these new variants--perhaps as a result of immunologic priming that
      occurred in childhood.

PMID- 2000848
TI  - Regression methods for estimating attributable risk in population-based case
      control studies: a comparison of additive and multiplicative models.
AB  - A regression method that utilizes an additive model is proposed for the
      estimation of attributable risk in case-control studies carried out in defined
      populations. In contrast to previous multivariate procedures for the estimation
      of attributable risk, which have utilized logistic regression techniques to
      adjust for confounding factors, the model assumes an additive relation between
      the covariates included in the regression equation. As an empirical example,
      additive and logistic models were fitted to matched case-control data from a
      population-based study of childhood astrocytoma brain tumors. Although both
      models fitted the data well, the additive model provided a more satisfactory
      estimate of the risk attributable to multiple exposures, in the absence of
      significant additive interaction. In contrast to the results from the logistic
      model, the adjusted estimates of the risk attributable to each factor included in
      the additive model summed to the overall estimate for all of the factors
      considered jointly. Thus, the additive approach provides a useful alternative to
      existing procedures for the multivariate estimation of attributable risk when the
      additive model is determined to be appropriate on the basis of goodness-of-fit.

PMID- 2000849
TI  - Re: "Issues in carrying out epidemiologic research in the elderly".

PMID- 2000850
TI  - Re: "Self-evaluated health and mortality among the elderly in New Haven,
      Connecticut, and Iowa and Washington Counties, Iowa, 1982-1986".

PMID- 2000851
TI  - Re: "Mild vitamin A deficiency and risk of respiratory tract diseases and
      diarrhea in preschool and school children in northeastern Thailand.

PMID- 2000852
TI  - When genius errs: R.A. Fisher and the lung cancer controversy.
AB  - R.A. Fisher's work on lung cancer and smoking is critically reviewed. The
      controversy is placed in the context of his career and personality. Although
      Fisher made invaluable contributions to the field of statistics, his analysis of
      the causal association between lung cancer and smoking was flawed by an
      unwillingness to examine the entire body of data available and prematurely drawn
      conclusions. His views may also have been influenced by personal and professional
      conflicts, by his work as a consultant to the tobacco industry, and by the fact
      that he was himself a smoker.

PMID- 2000853
TI  - Tobacco use and prostate cancer: 26-year follow-up of US veterans.
AB  - A 26-year follow-up of nearly 250,000 US veterans who responded to a
      questionnaire revealed 4,607 deaths from prostate cancer, providing the largest
      number of cases to date for evaluating relation to tobacco habits. Cigarette
      smokers had a significant increase in relative risk (RR = 1.18; 95% confidence
      interval 1.09-1.28) and a dose response reaching 1.51 among smokers of 40 or more
      cigarettes per day. Risks were elevated, but not significantly, among users of
      smokeless tobacco and pipe/cigar smokers. Despite limited data in the literature
      to support this finding, our study suggests that cigarette smoking may be related
      to prostate cancer, perhaps through its effect on sex hormone metabolism.

PMID- 2000854
TI  - Alcohol consumption and blood pressure in black adults: the Pitt County Study.
AB  - While there is a clear consensus in the epidemiologic literature on the direct
      association between alcohol consumption and blood pressure, the shape of this
      relation and its strength in blacks are uncertain. Therefore, the association
      between alcohol and blood pressure was examined in a community-based random
      sample of 1,784 black adults aged 25 to 50 years living in eastern North
      Carolina. These individuals were interviewed in 1988 for a study of psychosocial
      and dietary risk factors for elevated blood pressure. Alcohol consumption was
      estimated from responses to a food frequency questionnaire and was divided into
      four categories, which ranged from abstention (52% of the sample) to greater than
      or equal to seven drinks/week (12%). After adjustment for age and body mass, the
      systolic blood pressure of adults reporting greater than or equal to seven
      drinks/week exceeded that of nondrinkers by 6.8 mmHg for men and women (p less
      than 0.001). There was no evidence of a threshold effect, and similar patterns
      were observed for diastolic blood pressure. Being in the highest category of
      alcohol consumption was related to low socioeconomic status, lower social
      integration, and higher levels of socioeconomic stressors. These data are
      consistent with a graded association between alcohol and blood pressure in black
      adults and suggest the importance of social factors underlying this association.

PMID- 2000855
TI  - Bacteremia during diarrhea: incidence, etiology, risk factors, and outcome.
AB  - To determine the importance of bacteremia in hospitalized patients with diarrhea
      in Bangladesh, from September 1982 through August 1983 the authors obtained blood
      for culture from 1,824 patients who were suspected of having sepsis (44% of all
      admissions). Nontyphoid bacteremia occurred in 243 patients. The most common
      pathogens were the Enterobacteriaceae (n = 66 episodes), Staphylococcus aureus (n
      = 65), Pseudomonas aeruginosa and other non-glucose-fermenting bacilli (n = 50),
      Streptococcus pneumoniae (n = 40), and Haemophilus influenzae (n = 16). When
      compared with an equal number of control patients without bacteremia, bacteremic
      patients were significantly (p less than 0.05) more likely to be under 1 year of
      age (46.5% of bacteremic patients vs. 30.0% of control patients) and more often
      had abdominal tenderness (20.1% vs. 11.5%), hypoproteinemia (a serum protein
      level less than 60 g/liter) (58.9% vs. 42.9%), and a prior intravenous infusion
      (49.0% vs. 30.9%). The case-fatality rate was 29.7% in bacteremic patients versus
      7.8% in controls (relative risk (RR) = 3.8, p less than 0.001). Factors that were
      associated with an increased risk of death in bacteremic patients were infection
      with a Gram-negative pathogen (RR = 2.48), decreased peristalsis (RR = 2.66),
      hypoproteinemia (RR = 3.36), hypothermia (RR = 2.54), and hypotension (RR =
      2.19). Bacteremia appears to be an important link between diarrheal illness and
      death in Bangladesh. In children with diarrhea who are suspected of being septic,
      early implementation of antimicrobial therapy that is effective against the broad
      range of pathogens identified appears to be indicated.

PMID- 2000856
TI  - Environmental contamination in child day-care centers.
AB  - Enteropathogens associated with outbreaks of diarrhea in day-care centers are
      spread by the fecal-oral route through contaminated hands or environmental
      objects. This prospective study was undertaken to determine the prevalence of
      fecal coliform contamination in day care. Ten rooms in six centers housing 121
      children less than 2 years of age were studied for 13 weeks (February to May
      1988). Inanimate objects (n = 1,275), toy balls (n = 724), and hands (n = 954)
      were cultured 1-3 times per week. Fecal coliform contamination was common and was
      greater (p less than 0.05) for objects, toy balls, and hands of children in
      toddler compared with infant rooms. In five rooms in which clothes were worn over
      diapers, there was a significantly lower prevalence of fecal coliform
      contamination of toy balls (p less than 0.005), inanimate objects (p less than
      0.05), and hands (p less than 0.001) when compared with rooms in which
      overclothes were not worn. Occurrence of diarrhea was significantly associated
      with increased contamination of hands (p = 0.001). Stool and environmental
      isolates from individual rooms had the same plasmid patterns, which were unique
      to each center. In summary, fecal coliform contamination of environmental objects
      and hands of children and caregivers in day-care centers is common; toy balls can
      serve as sentinels of contamination; fecal coliform contamination can be
      significantly decreased by use of overclothes; and Escherichia coli strains from
      stool showed the same plasmid patterns.

PMID- 2000857
TI  - An outbreak of cryptosporidiosis in a day-care center in Georgia.
AB  - Diarrhea among the 11 million children attending day-care centers in the United
      States is common, but infection control of enteric pathogens in the day-care
      center setting remains a challenge. In August 1989, an outbreak of
      cryptosporidiosis was investigated at a day-care center in Georgia. A total of
      49% (39/79) of children and 13% (3/23) of staff members who submitted stool
      specimens were found to be infected with Cryptosporidium. A total of 77% (30/39)
      of infected children had mild-to-moderate diarrhea (median duration, 5 days).
      Children were at highest risk if they were less than age 36 months, in diapers,
      and not toilet trained. Serial stool specimens were collected from 12 infected
      children. After diarrhea had ceased, oocyst shedding continued in all children
      for a mean duration of 16.5 days. It is concluded that the prevalence of
      asymptomatic infections and the duration of shedding after the end of symptoms
      may previously have been underestimated. Cohorting or exclusion from the day-care
      center of children who are asymptomatic shedders is not practical, and the
      management of cryptosporidiosis in day-care centers remains a major challenge.

PMID- 2000858
TI  - Assessment of reporting consistency in a case-control study of spontaneous
      abortions.
AB  - Reporting consistency was examined in a case-control study of spontaneous
      abortion in Santa Clara County, California. Each case (n = 100) and two pregnant
      controls (n = 200), frequency-matched by last menstrual period, were interviewed
      twice: first after the case's spontaneous abortion (on average, 24 weeks after
      the last menstrual period) and again after completion of the controls'
      pregnancies (on average, 48 weeks after the last menstrual period). Because of
      concern about differential reporting of water consumption in regions with
      publicized water contamination, interviews included detailed questions about
      consumption of tap water and bottled water during pregnancy, as well as other
      exposures. Most factors such as caffeine consumption, cigarette smoking,
      employment, and pregnancy history were consistently reported between interviews
      and did not appear to be subject to differential reporting between cases and
      controls. When variables were examined by univariate analysis, controls deleted
      reports of tap water consumption (any vs. more) more often than did cases. There
      was also a suggestion of differential reporting of up to two glasses per day for
      tap water and bottle water consumption when they were examined as continuous
      variables. However, the degree of differential reporting was not sufficient to
      appreciably alter the measures of association between water consumption during
      pregnancy and spontaneous abortion.

PMID- 2000859
TI  - Reliability of the behavioral risk factor survey in a triethnic population.
AB  - The Behavioral Risk Factor Survey (BRFS) is a telephone interview used widely by
      the Centers for Disease Control (CDC) in conjunction with state health
      departments to measure prevalences and time trends for health-related behaviors.
      We assessed the reliability of those parts of the BRFS related to cardiovascular
      disease (smoking, diet, obesity, exercise, and hypertension) and demographics by
      readministering the BRFS in July and August of 1989 to 145 randomly selected
      subjects between 10 and 21 days following completion of an initial interview.
      Sampling and data collection closely followed CDC procedures. The retest samples
      comprised 49 whites, 43 blacks, and 53 Hispanics living in northern Manhattan in
      New York City. Group prevalences or means were compared at first and second
      interviews for six demographic variables and 12 behavioral risk factor variables
      for the samples as a whole and separately for each ethnic group. All of these
      comparisons were highly consistent, and none showed a statistically significant
      difference. At the individual level, Pearson or kappa correlations for 19
      questions related to demographics and behavioral risk factors other than diet
      were greater than or equal to 0.60 (p less than 0.001) for all except routine
      checkup in the past 2 years (kappa = 0.54; p less than 0.001) and blood pressure
      measured in the past 2 years (crude concordance, 96%; kappa = 0.23; p less than
      0.01). For 17 food items, correlations for frequency of consumption ranged from
      0.44 to 0.76 (p less than 0.01). For a composite index of diet "atherogenicity"
      based on the 17 food items, r = 0.62 (p less than 0.001). This test-retest
      reliability study of the BRFS showed high consistency at the group level and
      acceptable to high item reliability at the individual level for the parts of the
      BRFS related to demographics, cardiovascular behavioral risk factors, and a 17
      item nutrition module. Findings were generally consistent in all three ethnic
      groups.

PMID- 2000860
TI  - Changes in commingled body mass index distributions associated with secular
      trends in overweight among Danish young men.
AB  - The authors present results from a novel approach to understanding recent secular
      trends in overweight in terms of changes in underlying component distributions.
      On the basis of an examination of two large overlapping samples of Danish young
      men (ns = 16,557 and 21,747) spanning birth cohorts 1939-1958, the authors found
      evidence for two-component distributions, normal and overweight, in all cohorts.
      In cohorts born after 1940, the authors observed an increase in the size of the
      overweight component with no corresponding changes in overall mean or component
      means. On the basis of these results and other published reports, the authors
      speculate that the secular increase in overweight may be understood as a
      differential response to environmental change that may be mediated by genotype.
      The net effect appears to have been an increased penetrance in obesity-prone
      Danish young men.

PMID- 2000861
TI  - Re: "Body mass index versus height and weight in relation to blood pressure:
      findings for the 10,079 persons in the INTERSALT study".

PMID- 2000862
TI  - Re: "Editorial commentary: epidemiology and exposure to electromagnetic fields,"
      "a sobering start for the cluster busters' conference," and "counterpoint from a
      cluster buster".

PMID- 2000863
TI  - Re: "Kaposi's sarcoma in a cohort of homosexual and bisexual men: epidemiology
      and analysis for cofactors".

PMID- 2000864
TI  - Potential cost-avoidance with oral extended-release morphine sulfate tablets
      versus morphine sulfate solution.
AB  - The costs of acquiring, preparing, and administering morphine sulfate extended
      release tablets and morphine sulfate solution were compared. Pharmacists at an
      acute-care community hospital timed the pharmacy and nursing components of the
      process of preparing and administering single doses of morphine sulfate extended
      release tablets 60 mg and morphine sulfate solution 5 mg/mL. The labor cost of
      each step was determined by multiplying the mean time required to perform the
      task by the median of the wage scale for the person performing it. Acquisition
      costs and ancillary supply costs were determined, and the overall cost of each
      therapy was calculated. The total time required for providing single doses did
      not differ substantially. However, assuming a total daily morphine sulfate dosage
      of 120 mg, the time required for administering extended-release morphine sulfate
      tablets 60 mg twice daily was determined to be 8.90 minutes, compared with 23.44
      minutes for solution (4 mL of 5-mg/mL solution) six times daily. Thus, although
      the cost of acquiring extended-release tablets was considerably higher than that
      of solution, the total daily cost of therapy with tablets was less than half that
      of therapy with solution. The potential for cost avoidance and the clinical
      advantages associated with extended-release morphine sulfate tablets make this
      formulation an attractive therapeutic alternative.

PMID- 2000865
TI  - Compatibility of cefoperazone sodium and furosemide in 5% dextrose injection.
AB  - The compatibility of cefoperazone sodium and furosemide in 5% dextrose injection
      stored at two temperatures was studied. Cefoperazone sodium and furosemide were
      added to 5% dextrose injection to achieve a cefoperazone concentration of 10
      mg/mL and a furosemide concentration of 0.2 mg/mL. The admixture was stored in
      100-mL vented i.v. containers in the dark under refrigeration (4 degrees C) and
      at room temperature (25 degrees C); three containers were stored at each
      temperature. A 1-mL sample was taken from each i.v. container immediately after
      preparation and after 1, 2, 5, 10, 15, 20, and 25 days to be inspected visually,
      checked for pH value, and analyzed by a stability-indicating high-performance
      liquid chromatographic method. No color change or precipitation was observed in
      any sample at any time during the study. More than 95% of the initial
      concentrations of both drugs remained for five days at 4 degrees C but for only
      two days at 25 degrees C. Cefoperazone sodium was somewhat more stable than
      furosemide under the same storage conditions for 25 days; however, less than a 2%
      difference between the drugs was noted. Under the conditions of this study,
      cefoperazone sodium 10 mg/mL and furosemide 0.2 mg/mL in admixtures in 5%
      dextrose injection are stable for only two days at 25 degrees C and five days at
      4 degrees C.

PMID- 2000866
TI  - Compatibility of cefoperazone sodium and cimetidine hydrochloride in 5% dextrose
      injection.
AB  - The compatibility of cimetidine hydrochloride and cefoperazone sodium in 5%
      dextrose injection stored at two temperatures was studied. Cimetidine
      hydrochloride and cefoperazone sodium were reconstituted or diluted with 5%
      dextrose injection to form an admixture with a cimetidine concentration of 2
      mg/mL and a cefoperazone concentration of 5 mg/mL. The admixture was stored in
      100-mL vented i.v. containers in the dark at 4 and 25 degrees C; three containers
      were stored at each temperature. A 2-mL sample was taken from each container
      after 0.5, 0.75, 1, 6, 12, 24, and 48 hours of storage and visually inspected,
      tested for pH, and assayed by a stability-indicating high-performance liquid
      chromatographic method. Triplicate studies were done for each storage condition.
      At both temperatures, drug concentrations varied by less than 5% during the study
      period. No color change, precipitation, or cloudiness was observed for any of the
      solutions under any of the storage conditions. Cefoperazone sodium 5.0 mg/mL and
      cimetidine hydrochloride 2.0 mg/mL in admixtures in 5% dextrose injection are
      stable for 48 hours at 4 and 25 degrees C.

PMID- 2000867
TI  - Summary of 1990 Medicaid drug rebate legislation. ASHP Government Affairs
      Division.
AB  - Provisions of the federal Omnibus Budget Reconciliation Act of 1990 that are
      designed to control federal and state outlays for prescription drugs by requiring
      rebates from drug manufacturers to state Medicaid programs are described, and
      their potential effects on pharmacy practice in organized health-care settings
      are discussed. As of January 1, 1991, for a manufacturer's drug product line to
      be eligible for any coverage under Medicaid, the manufacturer must provide
      rebates to all state Medicaid programs. Health maintenance organizations are
      exempt from the law. Hospitals that dispense outpatient drugs to Medicaid
      patients under a formulary system and that bill Medicaid not more than purchase
      costs are exempt. The law requires no immediate action by hospitals and other
      organized care settings; action may be required when provisions of the law
      concerning drug-use review programs and patient counseling become effective. If a
      state enters a rebate agreement, its Medicaid plan must permit coverage of all of
      a manufacturer's prescription drug products, but the law does not affect
      formulary systems of individual health-care institutions. Formulary issues, the
      scope of hospital exemption, and pharmacist participation in DUR activities and
      patient counseling need to be clarified as state Medicaid plans are amended to
      comply with the law; pharmacists in organized health-care settings can best
      influence these changes through action at the state level.

PMID- 2000868
TI  - Environmental protection efforts by a home-care pharmacy.

PMID- 2000869
TI  - Survey of training, handling practices, and risk perceptions of Kentucky
      pharmacists working with antineoplastic agents.

PMID- 2000870
TI  - Use of an algorithm to evaluate published reports of adverse drug reactions.

PMID- 2000871
TI  - Visual compatibility of morphine sulfate and meperidine hydrochloride with other
      injectable drugs during simulated Y-site injection.

PMID- 2000872
TI  - Visual compatibility of insulin with secondary intravenous drugs in admixtures.

PMID- 2000873
TI  - Allogeneic bone marrow transplantation: procedures and complications.
AB  - Bone marrow transplantation (BMT) is discussed in terms of immunology,
      procedures, and complications and their treatment. Any patient with a disorder of
      the hematopoietic or immune system or a disease in which a transferable
      hematopoietic cell can supply a missing enzyme is a candidate for BMT. A priority
      in allogeneic BMT is the identification of a compatible donor through matching of
      human lymphocyte antigens (HLAs). The greater the disparity in HLAs, the greater
      the chance of rejection. The ideal donor is a monozygotic twin or an HLA-matched
      sibling, but only 30% of patients have such a donor. Before receiving the bone
      marrow infusion, patients must be conditioned to create space in the marrow for
      donor cells, suppress the immune system, and eradicate any tumor in patients with
      malignancies. Conditioning is achieved by the combination of total body
      irradiation and cyclophosphamide treatment; busulfan, etoposide, and cytarabine
      have also been used. For patients given unmanipulated marrow, the number of
      nucleated cells infused is about 3 X 10(8) per kilogram. Signs of engraftment are
      usually seen 14-21 days later. Toxic effects related to conditioning appear
      during this period and include infection, gastroenteritis, mucositis, and
      congestive heart failure. The most serious complication is graft-versus-host
      disease (GVHD), which can affect multiple organ systems. Prednisone,
      methylprednisolone, methotrexate, antithymocyte globulin, and cyclosporine have
      been used in an effort to prevent or treat GVHD. Bone marrow transplantation
      offers the chance of long-term survival to many patients with terminal disease,
      but associated morbidity and mortality rates remain high. Research is needed to
      address the problems of infection, leukemic relapse, and GVHD and the difficulty
      in obtaining and matching donors.

PMID- 2000874
TI  - Controlling investigational drug use in community hospitals.

PMID- 2000875
TI  - Idarubicin hydrochloride dosing guidelines might cause confusion.

PMID- 2000876
TI  - Institutional review boards and quality assurance activities.

PMID- 2000877
TI  - Home-care group needed within ASHP.

PMID- 2000878
TI  - Banned drugs in amateur athletics.

PMID- 2000879
TI  - Pharmacists and animal research.

PMID- 2000880
TI  - Incompatibility of ceftriaxone with vancomycin.

PMID- 2000881
TI  - Providing medication information as a professional obligation.

PMID- 2000882
TI  - Applying business principles to pharmaceutical care.

PMID- 2000883
TI  - Alternative work schedules for female pharmacists.
AB  - The impact of the increased proportion of women in pharmacy is discussed, and two
      leadership positions for which part-time work schedules were implemented are
      described. Issues associated with the increased representation of women include
      pharmacist shortages, loss of future leaders, decreased staff productivity
      related to inadequate day-care services, and a reduced earning potential of
      pharmacists. Many of these problems can be addressed by altering benefit packages
      and work schedules to enable employees to raise children while continuing to
      work. Specific strategies include legislation, day-care programs, flex time and
      flex scheduling, telecommuting, and the creation of alternative work schedules or
      permanent part-time positions. At the University of Michigan, a part-time
      position that combines faculty and clinical responsibilities has been in place
      since 1988. At The Washington Hospital Center, one of the three assistant
      director of pharmacy positions is part-time. The women in both positions have met
      or exceeded job performance requirements while raising a family. Issues raised by
      the increasing number of female pharmacists must be addressed by the profession.
      Part-time work schedules are one strategy for enabling female pharmacists to meet
      both their family and career responsibilities.

PMID- 2000884
TI  - Effect of an infusion device on the integrity of whole blood and packed red blood
      cells.
AB  - The effects of the Gemini PC-2 linear peristaltic infusion device on the
      integrity of packed red blood cells (RBC) and whole blood products are reported.
      Thirty-eight units of blood products were infused at rates of 999, 100, 50, and 5
      mL/hr under simulated clinical conditions. To evaluate the effect of hematocrit
      on cell survival, fresh and stored packed RBCs preserved with adenine-saline 3
      (AS-3) and fresh and stored packed RBCs and fresh and stored whole blood
      preserved with citrate-phosphate-dextrose-adenine 1 (CPDA-1) were used. No two
      units tested came from the same donor. Plasma potassium and plasma free
      hemoglobin concentrations were determined before and after simulated infusion for
      80 experimental runs. Preinfusion plasma potassium and free hemoglobin
      concentrations varied significantly among the blood products. Stored products
      were associated with higher plasma potassium and free hemoglobin levels than
      fresh units, both before and after infusion. Concentrations also differed
      significantly between AS-3-preserved and CPDA-1-preserved fresh and stored packed
      RBCs. Infusion did not change plasma potassium values appreciably under any
      conditions. Plasma free hemoglobin increased in the fresh products only. Donor
      specific differences were significant for potassium but not for free hemoglobin.
      There was no significant effect of infusion rate on either biochemical marker. In
      all the experimental runs, less than 0.01% of cells were lysed. The Gemini PC-2
      linear peristaltic infusion device delivered a variety of blood products at a
      wide range of infusion rates without inducing a substantial degree of hemolysis.

PMID- 2000885
TI  - Program to improve nurses' knowledge of pediatric emergency medications.
AB  - The effects of an educational program designed to improve nurses' knowledge of
      the use of emergency medications in the pediatric intensive-care unit (PICU) are
      reported. The clinical pharmacist for a six-bed PICU and a clinical nurse
      educator developed a program to assess and extend PICU nurses' knowledge of
      emergency medications with respect to calculations of bolus and continuous
      infusions, pharmacology, and proper dosage and administration route. The program
      consisted of a pretest, a pharmacology lecture, calculation problems, a hands-on
      practicum, and a posttest. Drugs covered were atropine sulfate, sodium
      bicarbonate, calcium gluconate, calcium chloride, dopamine hydrochloride,
      dobutamine hydrochloride, epinephrine hydrochloride, isoproterenol hydrochloride,
      lidocaine hydrochloride, sodium nitroprusside, and norepinephrine bitartrate. A
      retest was given 13 months after the pretest. The program was completed by 21
      nurses over seven months. There was a significant difference between the mean
      pretest score, 69.5%, and the mean posttest score, 87.3%, due to improvements in
      scores for the calculation questions. There was no significant difference in the
      mean time required to complete the pretest and the posttest. A significant
      correlation was observed between pretest score and months spent practicing in the
      PICU. Time to take the retest was significantly shorter than the posttest time,
      and scores continued to improve. An educational program developed cooperatively
      by pharmacy and nursing improved specific measures of PICU nurses' knowledge of
      emergency drugs.

PMID- 2000886
TI  - Isolation of a partial clone of desmoplakin-1 by antibody screening of a lambda
      gt11 library.
AB  - Desmoplakin-1 is a 280,000 dalton component of the intracellular portion of
      desmosomes. Complementary DNA (cDNA) coding for a portion of desmoplakin-1 was
      obtained by screening a lambda gt11 cDNA library constructed specifically for
      this purpose. A388 cells (a human skin squamous cell carcinoma cell line) were
      found to produce desmoplakin-1 and mRNA from this cell line was used to prepare a
      random primed cDNA library. Screening 60,000 recombinants of the library with an
      affinity purified anti-demoplakin-1 antibody resulted in initial identification
      of four clones from which one 1500 base pair clone was isolated by plaque
      purification. The identity of this desmoplakin clone was confirmed by
      demonstrating that antibody affinity purified on the protein product of the clone
      bound desmoplakins 1 and 2 in Western blots. Thus, the clone appears to code for
      the shared region of desmoplakins 1 and 2.

PMID- 2000887
TI  - Empiric antibiotic selection by physicians: evaluation of reasoning strategies.
AB  - The objectives of the study were to evaluate the appropriateness of empiric
      antibiotic selection by housestaff treating medical patients with bacteremia. The
      design was a prospective, observational study at a university-affiliated
      hospital. Seventy-eight patients with bacteremia were evaluated. A clinical grade
      of acceptable or not acceptable was assigned to each antibiotic prescription by a
      consensus panel. The consensus panel found that 34.6% of antibiotic prescriptions
      were unacceptable (clinical grade). At least one flaw in the chain of reasoning
      was found in 56.4% of the 78 cases evaluated. Assessment of the clinical setting
      was correct in 94.9% of the cases; the portal of entry was identified in 91%;
      adequate knowledge of the bacterial flora at the suspected site of infection was
      found in 69%; the diagnostic workup was appropriate in 81%, and the correct
      antibiotic susceptibility patterns were given in 72%. A correct chain of
      reasoning was more likely to result in an acceptable clinical grade than flawed
      reasoning (p less than 0.005). However, an appropriate antibiotic selection was
      made by some physicians despite flawed reasoning, and inappropriate antibiotic
      selection occurred in a few cases despite fautless reasoning. In 3.8% of cases,
      unexpected organisms appeared in blood culture. Prescription of broad spectrum
      antibiotics may then be learned response. If so, educational efforts that
      emphasize narrow, rather than broad spectrum prescribing may be inadequate to
      change physician prescribing habits.

PMID- 2000888
TI  - Brain uptake of glucose in diabetes mellitus: the role of glucose transporters.
AB  - It is not known if the diabetes-related reduction in blood-brain barrier (BBB)
      transport of glucose is due to a change in the functional capacity of
      transporters or to an as yet unidentified mechanism occurring at the plasma
      membrane or cytoplasm. To increase our understanding of this problem, the
      cerebral blood flow, the brain uptake index (BUI) of 3-O-methyl glucose and the
      concentration of 3H-cytochalasin B binding sites were determined in diabetic rats
      and diabetic rats treated with insulin. The BUI of 3-O-methyl glucose was
      significantly reduced (less than 0.001) in diabetic rats (32.7 +/- 1.2%) compared
      to control rats (41.9 +/- 1.0%). This change could not be attributed to an
      alteration in cerebral blood flow or to a non-specific change in BBB
      permeability. Normalization of blood glucose with insulin therapy corrected the
      BUI measurements in diabetic rats (42.2 +/- 1.4%). The level of measurable
      glucose transporters measured with 3H-cytochalasin B binding assay did not appear
      to be reduced in the diabetic brain microvessels. The data indicate that the
      reduced brain uptake of glucose in chronic hyperglycemia can occur in the absence
      of a change in glucose transporter concentration.

PMID- 2000889
TI  - Hypercalcemia with excess serum 1,25 dihydroxyvitamin D in lymphomatoid
      granulomatosis/angiocentric lymphoma.
AB  - Hypercalcemia has been described in a variety of granulomatous and
      lymphoproliferative disorders in association with elevated serum levels of 1,25
      dihydroxyvitamin D. In such cases, hypercalcemia appears to be the consequence of
      excessive production of 1,25(OH)2D by the lymphocyte/macrophage line. The authors
      report a patient with lymphomatoid granulomatosis/angiocentric lymphoma who
      developed hypercalcemia with extreme elevation in serum 1,25(OH)2D. Therapy with
      steroids reduced the serum calcium and 1,25(OH)2D levels to normal. Hypercalcemia
      has not previously been reported in lymphomatoid granulomatosis/angiocentric
      lymphoma. The distinctive features of this malignancy, and the derangement in the
      metabolism of 1,25(OH)2D in lymphoproliferative disorders in general, are
      discussed.

PMID- 2000891
TI  - Marked plasmacytosis and immunoglobulin abnormalities following infusion of
      streptokinase.
AB  - Marked plasmacytosis is an uncommon clinical finding associated with plasma cell
      dyscrasias and certain reactive states, particularly serum sickness. Moreover,
      serum sickness-like reactions are a well-recognized complication of therapy with
      streptokinase. In this report, the authors describe a patient who developed a
      transient, but striking, plasmacytosis and an unexplained fever following
      streptokinase treatment for a pulmonary embolus. An evaluation for multiple
      myeloma was completely negative except for the occurrence of serum monoclonal
      like proteins which largely disappeared over an eight month period.

PMID- 2000890
TI  - Pericardial metastasis from testicular seminoma: appearance and disappearance by
      echocardiography.
AB  - At the time of initial diagnosis, testicular malignancy is usually limited to the
      testicle and infradiaphragmatic lymph nodes. Metastases initially follow the
      retroperitoneal lymph channels and subsequently extend to the supradiphragmatic
      lymph nodes in the mediastinum and supraclavicular fossa. Testicular metastases
      to the pericardium are rare and usually asymptomatic. These lesions are most
      commonly identified at autopsy; therefore, the actual incidence is unknown. The
      authors report a 32-year-old man with testicular carcinoma, who developed
      asymptomatic pericardial metastases without concomitant supradiaphragmatic nodal
      or pulmonary metastases. They review the efficacy of echocardiography in
      diagnosis and follow up or pericardial metastasis.

PMID- 2000892
TI  - Aplastic anemia associated with antithyroid drugs.
AB  - Prognosis in aplastic anemia is usually linked to the degree of hypoplasia in the
      bone marrow and pancytopenia in the blood. The authors were, therefore, intrigued
      when a patient with methimazole-associated aplastic anemia who satisfied criteria
      for severe disease recovered rapidly and completely once her drug was withdrawn.
      Review of the English language literature revealed ten fully documented cases of
      aplastic anemia associated with use of the antithyroid drugs methimazole,
      carbimazole, and propylthiouracil. Analysis of the ten and of an eleventh case
      presented here indicated that the disorder is typically characterized by severe
      pancytopenia and profound marrow hypoplasia, yet surprisingly good prognosis, ie,
      minimum survival of more than 70% with partial or complete recovery from symptoms
      and cytopenias in survivors within 2-5 weeks. The only deaths, both in the 1950s,
      were from brain hemorrhage in patients who were not transfused with platelets.
      The discrepancy between the clinical and laboratory severity of antithyroid drug
      associated aplasia, on the one hand, and its relatively good prognosis and short
      term course, on the other, should be kept in mind when considering these patients
      for bone marrow transplantation or for therapy with antithymocyte globulin.

PMID- 2000893
TI  - Diabetic nephropathy: changing concepts of pathogenesis and treatment.
AB  - The metabolic changes which accompany hyperglycemia in a person with diabetes are
      thought to cause renal hyperperfusion and intraglomerular hypertension,
      especially in the person with a predisposition to essential hypertension.
      Intraglomerular hypertension causing deposition of protein in the mesangium leads
      to glomerulosclerosis and renal failure. Screening for microalbuminuria can
      predict which type I diabetic patients will develop nephropathy. The decline in
      renal function in established diabetic nephropathy can be slowed with aggressive
      treatment of hypertension. The use of ACE inhibitors may also decrease
      intraglomerular hypertension. Whether similar treatment in the person with
      preclinical diabetic nephropathy would delay or prevent the onset of diabetic
      nephropathy is being investigated. Restricted protein intake, anti-platelet and
      rheolitic drugs may have a role in the treatment of established diabetic
      nephropathy. In end stage renal failure, renal transplantation is the treatment
      of choice. When transplantation cannot be performed, chronic ambulatory
      peritoneal dialysis is preferable to hemodialysis.

PMID- 2000894
TI  - Neuromuscular disease of the gastrointestinal tract.
AB  - Gastrointestinal motility is the function of gastrointestinal smooth muscle. It
      is controlled by both the intrinsic and extrinsic nerves of the gastrointestinal
      tract and, to a lesser degree, the gastrointestinal hormones. Therefore, any
      abnormality of the above factors, theoretically, can cause gastrointestinal
      dysmotility. In a clinical situation, commonly seen is gastrointestinal
      dysmotility caused by either smooth muscle or intrinsic and extrinsic nerves
      dysfunction. Diseases that cause smooth muscle dysfunction include familial
      visceral myopathies, nonfamilial visceral myopathies, collagen disease, muscular
      dystrophies, amyloidosis, thyroid disease, and so on. Diseases that cause enteric
      nerve dysfunction include familial visceral neuropathies, nonfamilial visceral
      neuropathies, diabetes mellitus, Chagas' disease, ganglioneuromatosis of the
      intestine, visceral neuropathy of carcinomatosis, Parkinson's disease, and so on.
      The patients with neuromuscular disease of the gastrointestinal tract have a wide
      range of clinical manifestations regardless of the underlying cause. At one end
      of the spectrum, the patients may be asymptomatic, and at the other end of the
      spectrum, the patients may have functional obstruction of the gastrointestinal
      tract. Plain abdominal x-rays, upper gastrointestinal (UGI) and small bowel x
      rays, enteroclysis, barium enema, and manometric studies are useful for the work
      up of these patients. Enteroclysis is especially helpful in ruling out mechanical
      obstruction of the small intestine in patients with chronic intestinal pseudo
      obstruction. Treatment is mainly symptomatic and supportive. There is no
      effective drug to improve gastrointestinal motility. Surgery may be helpful in
      selected cases of severe gastrointestinal dysmotility.

PMID- 2000895
TI  - Gonococcal endocarditis: twenty-five year experience.
AB  - Gonococcal endocarditis is a devastating albeit rare complication of disseminated
      gonorrhea. It virtually disappeared as a disease entity with the advent of
      antibiotic therapy. Recently, it has reappeared with surprisingly high frequency
      for unclear reasons. Since 1983, the authors have observed six episodes of this
      disease in five patients, the largest series reported to date. It is
      predominantly a disease of young people without underlying valvular heart
      disease. Characteristic clinical features include a high frequency of congestive
      heart failure and nephritis and a proclivity for aortic valve involvement,
      commonly with associated ring abscess, and large vegetations. Genitourinary
      symptoms, arthralgias, and rash are uncommon. Previously undescribed features
      include involvement of all four valves simultaneously, recurrence on an aortic
      valve prosthesis, and a high frequency of terminal complement deficiencies.
      Precipitous hemodynamic deterioration despite appropriate therapy is not
      uncommon, and overall mortality rate remains an alarming 19%.

PMID- 2000896
TI  - The management of retinal detachments associated with choroidal colobomas by
      vitreous surgery.
AB  - We used vitreous surgery to treat seven patients (eight eyes) with complicated
      retinal detachments associated with choroidal colobomas. All eyes had large
      choroidal colobomas and no evidence of peripheral retinal breaks. Small, atrophic
      breaks were detected in five of the eyes and were located in the base of the
      coloboma in four of the five eyes. Adjunctive surgical techniques were necessary
      and included cyanoacrylate retinopexy in four eyes, silicone oil tamponade in
      five eyes, and retinectomy in two eyes. Retinal reattachment was ultimately
      attained in seven of the eight eyes. The number of surgical procedures ranged
      from one to five, with an average of three. Postoperative visual acuity of the
      eyes that underwent anatomically successful procedures ranged from 20/100 to
      light perception. Proliferative vitreoretinopathy was the most frequent cause of
      redetachment, occurring in six of the eight eyes.

PMID- 2000897
TI  - In vivo phosphorus 31 magnetic resonance spectroscopy of human uveal melanomas
      and other intraocular tumors.
AB  - We studied the feasibility of using the surface coil probe technique for the
      noninvasive in vivo study of ocular tumors by phosphorus 31 magnetic resonance
      spectroscopy. The characteristic organophosphate metabolites of suspected uveal
      melanomas before proton beam irradiation were determined qualitatively by
      phosphorus 31 magnetic resonance spectroscopy in vivo using a three-turn surface
      coil. Spectra of choroidal hemangioma, osteoma, and metastasis were also obtained
      in vivo and compared with those of uveal melanomas. Analysis of spectra performed
      at 1.5 T showed significant peaks of phosphomonoesters, inorganic phosphate,
      phosphodiesters, phosphocreatine, and adenosine 5'-triphosphates. The unusually
      high concentration of phosphodiesters may be considered as a marker for uveal
      melanomas and other choroidal tumors. By analyzing the ratio of phosphocreatine
      to phosphodiesters spectral area values, we interpreted qualitatively spectra of
      intraocular tumors to differentiate malignant tumors from benign lesions.
      Nevertheless, the main limitation of interpreting the spectra was their
      contamination by signals from surrounding tissues.

PMID- 2000898
TI  - Prevalence and association of asteroid hyalosis with systemic diseases.
AB  - We performed a cross-sectional study of 12,205 patients, which identified 101
      patients (0.83%) with asteroid hyalosis. These patients were examined for
      associated systemic and ocular conditions. Diabetes mellitus was found in 29 of
      the patients with asteroid hyalosis (29%), as compared to ten of 101 (10%)
      control subjects (P = .0007). An increased prevalence of systemic arterial
      hypertension (61 of 101 [60%] patients with asteroid hyalosis compared with 29 of
      101 [29%] control subjects; P = .0001) and atherosclerotic vascular disease (30
      of 101 [30%] patients with asteroid hyalosis compared with 13 of 101 [13%]
      control subjects; P = .006) was also discovered in the asteroid hyalosis group.
      Additionally, patients with asteroid hyalosis were found to be more hyperopic
      than control subjects (P = .009).

PMID- 2000899
TI  - Hereditary hemorrhagic macular dystrophy.
AB  - We treated two brothers who had a hemorrhagic macular lesion in one eye; a
      similar problem affected the fellow eye of both patients within eight months.
      Generalized fine granularity of the retinal pigment epithelium and peripheral
      iris transillumination defects were observed in both siblings. A study of the
      family suggested that the disorder was dominantly inherited and probably was
      Sorsby's pseudoinflammatory macular dystrophy. The macular lesions in one brother
      were treated by argon green laser photocoagulation and in the other brother by
      krypton red laser photocoagulation. Although the brother treated by krypton red
      laser photocoagulation attained better final visual function, additional
      differences in treatment methods also may have contributed to the final outcome.

PMID- 2000900
TI  - A simple transposition procedure for complicated strabismus.
AB  - We combined a recession or resection of recti muscles with a vertical or
      horizontal transposition to correct a complicated paralytic ocular deviation in
      eight patients. The transposed muscles were reattached to the globe parallel to
      the spiral of Tillaux and adjacent to the paralyzed muscle. Postoperatively,
      seven patients demonstrated fusion in the primary position or required a slight
      head turn to fuse. There were no surgical complications, and no patient developed
      symptomatic cyclotropia, diplopia, or anterior segment ischemia.

PMID- 2000901
TI  - Postoperative complications after Molteno implant surgery.
AB  - We performed Molteno implant surgery in one eye each of 41 patients with
      uncontrolled glaucoma. Intraocular pressure was controlled (intraocular pressure
      less than or equal to 18 mm Hg) in 32 eyes (78%). The mean preoperative
      intraocular pressure was 40 +/- 13.2 mm Hg, whereas the mean postoperative
      intraocular pressure was 16 +/- 6.6 mm Hg. Patients were followed up for an
      average of 16 months after the operation. Visual acuity was unchanged in 23 eyes
      (56%), improved in nine eyes (22%), and poorer in nine eyes (22%). The major
      complications included shallow anterior chamber and hypotony in six eyes (14.6%),
      vitreous hemorrhage in two eyes (4.9%), retinal detachment in one eye (2.4%), and
      malignant glaucoma in two eyes (4.9%). Less grave complications included hyphema
      in four eyes (9.8%), peripheral choroidal effusion in 15 eyes (36.6%),
      obstruction of the tube in six eyes (14.6%), recession of the tube into the angle
      in two eyes (4.9%), erosion of the tube in one eye (2.4%), and Tenon's cyst
      formation in three eyes (7.3%).

PMID- 2000902
TI  - A comparison of total and partial tenonectomy with trabeculectomy.
AB  - We compared the results of two methods of tenonectomy at the time of
      trabeculectomy. Of 49 eyes, 23 were randomly assigned to a partial tenonectomy
      and 26 to a total tenonectomy. There was no statistically significant difference
      in the success rate between the two surgical groups using an upper limit of
      intraocular pressure of either 18 or 21 mm Hg as the criterion for success. There
      was no difference in the need for postoperative medications or further surgical
      intervention between the two groups. Although certain advantages exist with each
      technique, these findings suggest that equivalent results can be anticipated with
      either a total or partial tenonectomy.

PMID- 2000903
TI  - Therapeutic ultrasound for the treatment of glaucoma.
AB  - A multicenter clinical trial of therapeutic ultrasound for the treatment of
      glaucoma included 20 centers in the United States in which 1,117 treatments were
      performed on 880 eyes. The study was limited to patients with refractory glaucoma
      who had not benefited from conventional medical and surgical techniques.
      Approximately 782 of 1,117 treatments (70%) showed an initial decrease in
      intraocular pressure from a pretreatment mean of 38.1 mm Hg to 22 mm Hg or less.
      By Kaplan-Meier survival analysis, the single treatment success rate (intraocular
      pressure between 6 and 22 mm Hg) was 48.7% at six months posttreatment. When
      retreatment was used subsequent to failure, the one-year multitreatment success
      rate was 79.3%. The most common complications were an immediate posttreatment
      intraocular pressure increase lasting a few hours and mild iritis. Other
      complications included scleral thinning in 28 of 1,117 treatments (2.5%) and
      phthisis bulbi in 12 of 1,117 treatments (1.1%).

PMID- 2000904
TI  - A physical analysis of the factors that determine the contour of the iris.
AB  - By solving equations that result from the application of basic newtonian physical
      principles, I developed a model that can predict the profile of the iris by using
      only the pupil radius, the iris root radius, and the anterior displacement of the
      pupil from the iris root. The model requires some theoretically and clinically
      reasonable assumptions regarding the relative importance of forces acting on the
      iris. Former analyses made false assumptions about contact between the lens and
      the iris, as well as inappropriate substitution of the physical concept of force
      for tension. The validity of the new model and its inherent assumptions can now
      be tested with biometric measurements made in normal eyes and eyes with shallow
      anterior chambers.

PMID- 2000905
TI  - The physiologic characteristics of relative pupillary block.
AB  - In biometric photographs of 13 patients, we quantified the iris contour in eyes
      with central anterior chamber depths ranging from 1.9 to 3.4 mm (epithelium to
      lens surface). This actual profile was compared to that predicted by a
      theoretical analysis of the forces acting on the iris. The average discrepancy
      between the calculated actual and the theoretically predicted iris position was
      only -0.01 to +0.03 mm. The close agreement validates the model under normal
      conditions and in the presence of relative (nonsynechial) pupillary block. The
      theoretical iris shape may not occur under conditions that violate the underlying
      physical assumptions of the mathematical model, such as when iridectomy
      eliminates the pressure difference between the anterior and posterior chamber or
      when synechiae introduce additional forces on the iris other than the ones
      included in the analysis.

PMID- 2000906
TI  - The epidemiologic association of Fuchs' heterochromic iridocyclitis and ocular
      toxoplasmosis.
AB  - Between January 1983 and July 1987, I examined 25 patients at the Department of
      Ophthalmology, West Virginia University, who had the anterior segment
      characteristics of Fuchs' heterochromic iridocyclitis. Of these patients, 16 had
      fundus lesions suggestive of ocular toxoplasmosis. Of these 16 patients, 13 had a
      positive serologic test for toxoplasmosis, two patients were not tested, and one
      patient had a negative test at 1:16. The remaining nine patients with Fuchs'
      heterochromic iridocyclitis had no fundus lesions suggestive of toxoplasmosis. A
      chart review of 792 consecutive patients at the Retinal Unit, West Virginia
      University, during a six-month period disclosed that 24 of 590 patients (4%) had
      chorioretinal scars suggestive of toxoplasmosis. I concluded from these data that
      in at least one subgroup of patients with Fuchs' heterochromic iridocyclitis
      there is a significant association with the chorioretinal scars of toxoplasmosis
      (P less than .01), and this is suggestive of a causal relationship.

PMID- 2000907
TI  - In defense of animal research.

PMID- 2000908
TI  - Aberrant extraocular fibrous band as a cause of strabismus.

PMID- 2000909
TI  - Large refractive change after strabismus surgery.

PMID- 2000910
TI  - Mean visual acuity.

PMID- 2000911
TI  - Infectious crystalline keratopathy after relaxing incisions.

PMID- 2000912
TI  - Immunofluorescence findings in pseudopemphigoid induced by short-term idoxuridine
      administration.

PMID- 2000913
TI  - Keratoconjunctivitis sicca caused by diphenoxylate hydrochloride with atropine
      sulfate (Lomotil)

PMID- 2000914
TI  - The oculocardiac reflex during enucleation.

PMID- 2000915
TI  - Endogenous Candida species endophthalmitis associated with increased levels of D
      arabinitol in serum and vitreous.

PMID- 2000916
TI  - Unilateral manifestation of the Vogt-Koyanagi-Harada syndrome in a 7-year-old
      child.

PMID- 2000917
TI  - Changes in corneal curvature at different excimer laser ablative depths.

PMID- 2000918
TI  - Anisocoria in the pigmentary dispersion syndrome.

PMID- 2000919
TI  - A comparison of craft use and academic preparation in craft modalities.
AB  - The purpose of this study was to compare the use of crafts in psychiatric
      occupational therapy practice with the actual craft-related training received by
      occupational therapy students. Two questionnaires were developed, one related to
      the crafts used in clinical practice, the other related to the amount and type of
      craft training received in educational programs. One thousand occupational
      therapists who work in psychiatry and 139 accredited and developing educational
      programs were asked to complete the questionnaire appropriate to their setting.
      The final analysis involved 121 educational programs (87% response rate) and 384
      clinical programs (38% response rate). The results suggest that there may be
      substantial differences between craft-related training and actual clinical use of
      crafts. The findings imply that educational programs must reevaluate the types of
      crafts taught and the method by which they are integrated into the total
      curriculum. Implications for the profession include the need to clarify the role
      of crafts as a therapeutic modality and to reflect on the future direction of the
      profession.

PMID- 2000920
TI  - Current concepts of children's perceptions of control.
AB  - Beliefs about control have been identified as an important aspect of the
      occupational therapy evaluation process because of their potential influence over
      the course of action chosen. This paper reviews the current status of research
      and theory in this area as it relates to children. Issues addressed include the
      drawbacks of the downward extension of adult theoretical models and tests to
      children, the multidimensionality of perceived control, and the relation between
      cognitive development and changes in beliefs. Recent revisions in theoretical
      models and new measures that provide more differentiated information on
      children's beliefs about causality and personal efficacy are reviewed. The
      implications for the selection of instruments and interpretation of results for
      the assessment of children's perceived control in clinical practice are
      discussed.

PMID- 2000921
TI  - Perceptions of role assessment tools in the physical disability setting.
AB  - Various role assessment tools in occupational therapy have been developed to help
      the clinician understand role performance and role adjustment and guide the
      structure of intervention. This study was designed to examine the clinician's
      perceptions of standardized role assessment tools in physical disability
      settings. A random sample of 450 occupational therapists was surveyed to learn
      about therapists' knowledge of four published role assessment tools. The study
      also examined the frequency of tool use in the acute care hospital, the
      rehabilitation center, and the long-term care facility. The results from 236
      questionnaires (a 52% response rate) indicated that more than half of the
      respondents reported that their current initial evaluation did not effectively
      address role performance. Additionally, most of the therapists surveyed had a
      poor understanding of the four standardized role assessment tools, and only 5%
      were using an assessment instrument in their practice. The respondents reported a
      desire to learn more about these instruments and how they affect treatment
      planning. Training implications, educational opportunities, and recommendations
      for future research are discussed.

PMID- 2000922
TI  - A prevention model for occupational therapy.
AB  - The role of occupational therapy in prevention has received much discussion but
      relatively little empirical testing and model building. Because of the evidence
      linking stress and illness, the life stress process has become a popular area of
      investigation. More importantly, a role strain model can provide a theoretical
      guide to occupational therapy practice due to the central importance of adaptive
      behavior and social competence. To illustrate, the maternal stress study is
      presented as an example of prevention research that examines the relationship
      between maternal stress and child psychopathology. Risk factors are identified as
      the first step in reliable case finding and the design of preventive
      interventions. Such model building can help occupational therapists develop
      prevention services for vulnerable populations.

PMID- 2000923
TI  - Wrist extensor orthoses: dexterity and grip strength across four styles.
AB  - Orthoses that are used to stabilize, protect, and support the wrist during
      functional activities often interfere with normal movement and, therefore, with
      hand function. This study compared the manual dexterity and grip strength of 20
      female subjects while using a free hand and while wearing each of four wrist
      extensor orthoses: a Futuro prefabricated wrist brace (No. 33), a volar thumbhole
      orthosis, a volar orthosis with a radial connector bar, and a dorsal orthosis
      with distal transverse arch support. Of these orthoses, the Futuro prefabricated
      wrist brace afforded the best overall dexterity, although it was significantly
      slower (p less than .05) than the other orthoses in a writing subtest. Of the
      custom-made orthoses, the volar style with radial connector bar afforded the best
      overall dexterity. All of the orthoses significantly (p less than .01) reduced
      grip strength. The Futuro prefabricated wrist brace afforded the strongest grip
      strength of the four orthoses studied, and the volar thumbhole orthosis permitted
      the strongest grip among the custom-made orthotic styles.

PMID- 2000924
TI  - Reliability of three clinical measures of muscle tone in the shoulders and wrists
      of poststroke patients.
AB  - Muscle tone was tested at the shoulders and wrists of 49 randomly selected
      poststroke patients with the use of resting joint position (SJP and WJP),
      resistance to passive movement or stiffness (SRM and WRM), and angle of
      appearance of resistance (SAR and WAR). Subjects were tested while seated with
      their arm supported in a suspension sling adapted for free movement. Five of the
      first and immediately repeated measurement pairs showed strong correlations and
      interrater reliability (SJP, .839; WJP, .900; SRM, .886; WRM, .904; SAR, .884 [p
      less than .05]). The sixth (WAR) showed moderate reliability (.618, p less than
      .05). Resting joint position measurements were most reliable among subjects with
      higher tone. The joint first measured had a slight order effect on SRM among
      subjects with higher muscle tone. Its second measurements were slightly increased
      over the first among those subjects whose shoulders were measured first and
      slightly reduced when measured immediately after the wrist. Reliable means of
      clinical evaluation of muscle tone at the shoulder and wrist are available if the
      influence of level of tone and the mutual influence of muscles tested are
      prudently considered.

PMID- 2000925
TI  - Therapeutic factors in occupational therapy groups.
AB  - A survey was administered to patients and their therapists in an attempt to
      assess which therapeutic factors were perceived as helpful in occupational
      therapy groups. The patients' responses were compared to their therapists' for
      similarities and differences. Both groups highly valued factors of group
      cohesiveness, instillation of hope, and interpersonal learning. The therapists
      also valued guidance and identification, which the patients did not. Least valued
      by the patients were guidance, existential factors, and identification; least
      valued by the therapists were self-understanding, family reenactment, and
      existential factors.

PMID- 2000926
TI  - Spatial disorientation in persons with early senile dementia of the Alzheimer
      type.
AB  - Although spatial disorientation is frequently observed in persons with Alzheimer
      disease, it is not well understood. A descriptive study was conducted to examine
      spatial skills associated with spatial orientation. Spatial tasks were selected
      and grouped into three types of spatial skills: perceptual, cognitive, and
      functional. These spatial tasks were administered to a group of 15 persons with
      senile dementia of the Alzheimer type (SDAT) (early Alzheimer disease) and a
      group of 15 control subjects. The results indicated that the subjects with SDAT
      were impaired on half of the perceptual spatial tasks and all of the cognitive
      spatial tasks. On the functional spatial tasks, however, the subjects with SDAT
      showed impaired skills in the new environment but intact skills in familiar
      environments. Spatial disorientation poses a danger and limits a person's ability
      to independently perform daily activities that require navigation outside of the
      home. Occupational therapy should therefore include the assessment of spatial
      orientation skills in persons who are in the early stages of dementia.

PMID- 2000927
TI  - Directions for the future: opportunities for leadership.

PMID- 2000928
TI  - Evaluating movement for switch use in an adult with severe physical and cognitive
      impairments.
AB  - Miranda's family members are most supportive of the goal for her to have a
      powered wheelchair and encourage her when they visit. Motivation has been the key
      to Miranda's success at learning to operate switches in order to explore and
      learn from her environment. As long as the outcome available from operation of a
      switch is desirable for Miranda, she works hard at controlling her movements so
      as to activate it. Conversely, if the ultimate advantage of operating the switch
      is unclear to her, she is unwilling to make the effort. The occupational
      therapist's role is crucial, in that she realizes the importance of motivation
      and consequently designs activities and rewards that are important and meaningful
      for Miranda. Miranda's life has been considerably enriched by the introduction of
      mechanical aids into her leisure sphere. She has become more interested in her
      surroundings and is excited about exploring possibilities for future rewarding
      activities, such as academics. A notable additional benefit has been that Miranda
      now displays a more assertive attitude on her own behalf.

PMID- 2000929
TI  - Tenodesis brace use by persons with spinal cord injuries.

PMID- 2000930
TI  - Facilitating balance between career and family: a crucial challenge.

PMID- 2000931
TI  - The term restraints is archaic.

PMID- 2000932
TI  - Ovarian granulosa-stromal cell tumors are characterized by trisomy 12.
AB  - Eleven ovarian granulosa-stromal cell tumors including 1 thecoma, 2 fibromas, 6
      fibrothecomas, and 2 granulosa cell tumors, were karyotyped after direct harvest
      and/or short-term tissue culture. Bilateral fibrothecomas from one patient
      appeared to lack cytogenetic aberrations: the remaining nine tumors were
      characterized by trisomy for chromosome 12. Cytogenetic aberrations in the two
      granulosa cell tumors were much less complex than those described previously in
      undifferentiated carcinomas; accordingly cytogenetic analyses might be useful in
      distinguishing these categories. The consistent occurrence of trisomy 12 in
      different varieties of granulosa-stromal cell tumors suggests a common mechanism
      of oncogenesis within this diverse group of neoplasms. That mechanism probably
      involves promotion of low-grade, orderly cell proliferation.

PMID- 2000933
TI  - Is oncofetal fibronectin a trophoblast glue for human implantation?
AB  - Using an antibody probe specific for the class of fibronectins that contain the
      oncofetal domain, it was shown that oncofetal fibronectin (onfFN) is present
      wherever trophoblasts make contact with extraplacental extracellular matrix
      (ECM). In normal human implantation sites, onfFN was localized to a highly
      specific region-the ECM connecting extravilous trophoblasts and trophoblastic
      cell columns to the uterine decidua. This same zone of onfFN was present in an
      analogous location in extrauterine gestations. Like these in vivo extravillous
      trophoblasts, isolated cytotrophoblasts in primary culture synthesized and
      secreted onfFN as they underwent differentiation. Furthermore, when cocultured
      with an ECM gel, cytotrophoblast aggregates deposited onfFN at cell-ECM contact
      sites, resembling early implanting trophoblasts in vivo. In the presence of
      cyclic AMP agonists, onfFN synthesis was inhibited markedly. It is concluded from
      these results that onfFN is a trophoblast protein that, under cAMP regulation,
      could mediate implantation and placental-uterine attachment throughout gestation.

PMID- 2000935
TI  - Development of intrapancreatic transplantable model of pancreatic duct
      adenocarcinoma in Syrian golden hamsters.
AB  - Intrapancreatic and subcutaneous (SC) inoculation of cultured pancreatic cancer
      cells, derived from an induced primary pancreatic cancer in a Syrian hamster,
      resulted in tumor take in all recipient hamsters. The intrapancreatic allografts
      grew rapidly, were invasive, and metastasized into the lymph nodes and liver in 2
      of 9 cases. In comparison, SC tumors grew relatively slower and formed a large
      encapsulated mass without invasion and metastases. Histologically, tumors of both
      sites showed fairly well-differentiated adenocarcinomas of ductal/ductular type
      resembling the induced primary cancer. Similar to the primary induced pancreatic
      cancers, tumor cells of both allografts expressed blood-group-related antigens,
      including A, B, H, Le(b), Le(y), Le(x), and tumor-associated antigen TAG-72. The
      tumor cells did not express Le(a), CA 19-9, 17-1A, or DU-PAN-2. The expression of
      these antigens was retained in the metastases and presented the same patterns of
      reactivity as the allografts. Thus intrapancreatic transplantation provides a
      rapid model for production of pancreatic cancer with morphologic similarities to
      human pancreatic cancer.

PMID- 2000934
TI  - Effects of the phospholipase inhibitor mepacrine on injury in ischemic and
      metabolically inhibited adult isolated myocytes.
AB  - The phospholipase inhibitor mepacrine has been shown to delay cell death of
      metabolically inhibited cultured cardiomyocytes. The present study was initiated
      to determine if mepacrine also delays cell death and development of osmotic
      fragility of both metabolically inhibited and ischemic adult rat cardiomyocytes.
      Isolated myocyte suspensions were incubated with 3 mmol/l (millimolar) iodoacetic
      acid and 6 mmol/l amytal (inhibited) or were pelleted into a slurry and layered
      with oil (ischemic) in the presence and absence of 10 or 50 mumol/l (micromolar)
      mepacrine. Rates of contracture, cell viability as determined by trypan blue
      permeability, cell viability after osmotic swelling in 170 mOsm media (osmotic
      fragility), and cell morphology were monitored. Mepacrine had no effects on rates
      of contracture, but was found to significantly delay cell death during isotonic
      incubations of both metabolically inhibited and ischemic cells. In contrast,
      mepacrine had no effect on the development of osmotic fragility. Incubation of
      metabolically inhibited myocytes in calcium-free media did not delay contracture
      or cell injury, but did attenuate the protective effects of mepacrine. This study
      confirms previous reports that mepacrine protects cells from injury, extends the
      observations of protection to ischemic isolated adult myocytes, but shows that
      development of osmotic fragility is not inhibited by mepacrine.

PMID- 2000936
TI  - Three-dimensional cytoarchitecture of normal and atherosclerotic intima of human
      aorta.
AB  - The three-dimensional cytoarchitecture of normal and atherosclerotic intima of
      human aorta was studied by light microscopy of consecutive en face preparations
      (Hautchen preparations) and by scanning electron microscopy. In unaffected
      intima, a three-dimensional network consisting of cells of variable shape and
      probably origin was demonstrated. Cellular shape changed from predominantly
      stellate in the luminal regions of the elastic-hyperplastic layer to elongated
      spindlelike cells in the musculoelastic layer of the intima. In the surface
      layers of the fatty streak, cellular contacts were severed, and lipid droplets
      were often seen between cellular processes. Along with stellate and elongated
      cells, the fatty streak also had a number of round monocytelike cells. Lipid
      inclusions were usually detected in stellate and ovoid cells. The integrity of
      the cellular network was preserved at the marginal zone of the atherosclerotic
      plaque, while at the slopes and in the central part of the plaque, cells
      practically lost all contact with each other. Giant stellate cells embedded in
      crude fibrillar connective tissue matrix were often found there. Disintegration
      of the cellular network during atherosclerosis is suggested to play an important
      role in the development of various lesions.

PMID- 2000937
TI  - Contrasting roles for tumor necrosis factor in the pathogeneses of IgA and IgG
      immune complex lung injury.
AB  - Recent studies suggest that development of acute gamma G immunoglobulin (IgG)
      immune complex lung injury is partially dependent on a tumor necrosis factor
      (TNF)-dependent mechanisms of neutrophil (PMN) recruitment. The authors have
      sought to further define the role of intrapulmonary TNF in IgG alveolitis and to
      examine its role in IgA immune complex alveolitis, a neutrophil-independent model
      of acute lung injury. IgG immune complex lung injury resulted in a marked rise in
      intrapulmonary TNF activity accompanied by progressive pulmonary PMN
      accumulation. Intratracheal instillation of neutralizing concentrations of anti
      TNF markedly reduced PMN influx measured at 4 hours but had no effect on PMN
      recruitment quantitated at 2 hours. IgA immune complex deposition resulted in
      acute lung injury accompanied by increased numbers of intrapulmonary mononuclear
      phagocytes but few neutrophils. Lung lavage fluids obtained from IgA immune
      complex-injured rats contained both neutrophil and monocyte chemotactic
      activities, albeit at twofold to fourfold lower concentrations than observed in
      IgG-mediated alveolitis. In contrast to IgG complex-mediated alveolitis, lung
      lavage fluids from IgA-injured rats contained no TNF activity. Intratracheal
      administration of anti-TNF antibodies had no effect on the development of IgA
      lung injury as assessed by morphology and measurements of vascular permeability.
      In vitro exposure of isolated alveolar macrophages to performed IgG immune
      complexes resulted in dose-dependent TNF secretion, while exposure to IgA
      complexes resulted in very low levels of TNF secretion. These data suggest that
      TNF-mediated pulmonary neutrophil recruitment (in IgG lung injury) is manifest
      chiefly in the late phase (approximately 4 hours) of developing alveolitis. The
      virtual absence of intrapulmonary TNF activity in evolving IgA immune complex
      alveolitis may in part account for the limited PMN recruitment observed in this
      model.

PMID- 2000938
TI  - Minimally oxidized low-density lipoprotein induces tissue factor expression in
      cultured human endothelial cells.
AB  - Oxidatively modified low-density lipoprotein is present in atherosclerotic
      lesions and has been proposed to play an important role in atherogenesis through
      its biologic effects on vascular cells. This study examined the effects of
      minimally oxidized preparations of LDL (MM-LDL) on tissue factor (TF) expression
      by cultured human endothelial cells. Low-density lipoprotein purified from normal
      donors was modified by exposure to iron or by prolonged storage, resulting in
      levels of thiobarbituric acid-reacting substances of approximately 2.5 to 4
      nmoles/mg cholesterol. Preparations had less than 2.5 pg of endotoxin per
      microgram LDL and had no intrinsic procoagulant activity. This form of modified
      but not native LDL induced TF expression in endothelial cells in a time- and dose
      dependent manner. Peak TF coagulant activity in cells exposed to 40 micrograms/ml
      MM-LDL were observed at 4 to 6 hours, and ranged from 50 to 500 pg/10(5) cells,
      compared with less than 10 pg/10(5) cells exposed to native LDL. Northern blot
      analysis showed TF mRNA levels to increase approximately 30-fold with exposure to
      MM-LDL for 2 hours. Induction of TF activity was dependent on the concentration
      of MM-LDL from 1 microgram/ml to 80 micrograms/ml, a range in which cell
      viability and morphology were unaffected. The findings suggest that minimally
      oxidized LDL may be a local mediator promoting thrombosis in atherosclerotic
      lesions.

PMID- 2000939
TI  - S-100 protein antibodies do not label normal salivary gland myoepithelium.
      Histogenetic implications for salivary gland tumors.
AB  - Neoplastically modified myoepithelial cells have a key role in developing the
      histologic characteristics of some salivary gland tumors. S-100 protein expressed
      in certain of these tumors is suggested to support this role, as the principal
      component in the human salivary gland reported to be S-100 protein-positive is
      myoepithelium. Confirmation of such an important aspect is required.
      Immunoperoxidase staining of parotid salivary gland shows considerably different
      patterns obtained with antibodies to S-100 protein, neuron-specific enolase, and
      neurofilaments compared with those for muscle-specific actin and cytokeratin 14;
      many more cells and their processes associated with acini and ducts are evident
      with the latter two antibodies. Double immunofluorescent staining with antibodies
      to either S-100 protein or neuron-specific enolase combined with muscle-specific
      actin does not reveal colocalization of these antigens in myoepithelial cells.
      The former localize only to nerve fibers adjacent to, but separate from, acini,
      and the latter only to myoepithelial cells. It is apparent that S-100 protein
      staining of the rich network of unmyelinated nerves in the interstitial tissues,
      evident ultrastructurally, has been misinterpreted as myoepithelium. This result
      has important implications for histogenetic classifications of salivary gland
      tumors.

PMID- 2000940
TI  - Platelet-derived growth factor-BB and transforming growth factor beta 1
      selectively modulate glycosaminoglycans, collagen, and myofibroblasts in
      excisional wounds.
AB  - Recombinant platelet-derived growth factor (PDGF) and transforming growth factor
      beta 1 (TGF-beta 1) influence the rate of extracellular matrix formed in treated
      incisional wounds. Because incisional healing processes are difficult to
      quantify, a full-thickness excisional wound model in the rabbit ear was developed
      to permit detailed analyses of growth-factor-mediated tissue repair. In the
      present studies, quantitative and qualitative differences in acute inflammatory
      cell influx, glycosaminoglycan (GAG) deposition, collagen formation, and
      myofibroblast generation in PDGF-BB (BB homodimer)- and TGF-beta 1-treated wounds
      were detected when analyzed histochemically and ultrastructurally. Although both
      growth factors significantly augmented extracellular matrix formation and healing
      in 10-day wounds compared with controls (P less than 0.002). PDGF-BB markedly
      increased macrophage influx and GAG deposition, whereas TGF-beta 1 selectively
      induced significantly more mature collagen bundles at the leading edge of new
      granulation tissue (P = 0.007). Transforming growth factor-beta 1-treated wound
      fibroblasts demonstrated active collagen fibrillogenesis and accretion of
      subfibrils at the ultrastructural level. Myofibroblasts, phenotypically modified
      fibroblasts considered responsible for wound contraction, were observed in
      control, but were absent in early growth-factor-treated granulating wounds. These
      results provide important insights into the mechanisms of soft tissue repair and
      indicate that 1) PDGF-BB induces an inflammatory response and provisional matrix
      synthesis within wounds that is qualitatively similar but quantitatively
      increased compared with normal wounds; 2) TGF-beta 1 preferentially triggers
      synthesis and more rapid maturation of collagen within early wounds; and 3) both
      growth factors inhibit the differentiation of fibroblasts into myofibroblasts,
      perhaps because wound contraction is not required, due to increased extracellular
      matrix synthesis.

PMID- 2000941
TI  - Murine retroviral neurovirulence correlates with an enhanced ability ofvirus to
      infect selectively, replicate in, and activate resident microglial cells.
AB  - To determine the biologic basis of ts1 MoMuLV neurovirulence in vivo, newborn
      CFW/D mice were inoculated with neurovirulent ts1 MoMuLV and nonneurovirulent wt
      MoMuLV and the temporal response to virus infection in the central nervous system
      (CNS), spleen, and thymus was studied comparatively. Experimental procedures
      included single and double labeling in situ immunohistochemistry with selective
      morphometric analyses, and steady state immunoblotting of viral proteins.
      Cellular targets for virus infection were identical for both ts1 and wt MoMuLV
      and consisted sequentially of 1) splenic megakaryocytes, 2) splenic and thymic
      lymphocytes, 3) CNS capillary endothelial cells, and 4) CNS pericytes and
      microglia. Resident microglial cells served as the major reservor and amplifier
      of virus infection in the CNS of ts1 MoMuLV-infected mice; a similar but much
      less significant role was played by microglia in wt MoMuLV-infected mice. The
      genesis and progression of severe spongiform lesions in ts1 MoMuLV-infected mice
      were both temporally and spatially correlated with amplified virus infection of
      microglia, and hyperplasia and hypertrophy of both virus-infected and nonvirus
      infected microglial cells. Direct virus infection of neurons was never observed.
      The development of clinical neurologic disease and spongiform lesions in ts1
      MoMuLV-infected mice correlated with the accumulation of both viral gag and env
      gene products in the CNS; there was no selective accumulation of env precursor
      polyprotein Pr80env. When compared to wt MoMuLV-infected mice, the neurovirulence
      of ts1 MoMuLV-infected mice occurred by an enhanced ability to replicate in the
      CNS and to infect and activate more microglia, rather than by a fundamental
      change in cellular tropism or topography of virus infection.

PMID- 2000942
TI  - Hairless micropig skin. A novel model for studies of cutaneous biology.
AB  - Reported here is the structural and immunohistochemical similarities between the
      Yucatan hairless micropig (HMP) skin and that of humans. Hairless micropig skin
      surface was composed of complex intersecting furrows that created geometric
      patterns remarkably similar to human skin surface glyphics. The dermal--epidermal
      interface consisted of undulant downgrowths that interdigitated with dermal
      papillae. Hairless micropig epidermis contained two morphologically distinct
      populations of basal keratinocytes (serrated and nonserrated). Similar
      heterogeneity has been seen only in human epidermis and primate palmar epidermis.
      Immunohistochemistry revealed that the HMP epidermis is reactive with monoclonal
      and polyclonal antisera to keratin proteins. Melanocytes reactive with antisera
      to S-100 protein, as in human skin, also were observed in HMP epidermis.
      Organization of dermal extracellular matrix, including collagen and elastic
      fibers, and the organization and reactivity of the microvasculature with antisera
      to factor VIII, were consistent with human skin. The costicosteroid-induced
      atrophy and subsequent rebound phenomenon after withdrawal of steroid observed in
      HMP skin was similar with that observed in humans. It is concluded that HMP skin
      approximates human skin significantly more precisely than most existing species
      and is an excellent model for studies of cutaneous physiology and pharmacology.

PMID- 2000943
TI  - The effects of monocrotaline pyrrole on cultured bovine pulmonary artery
      endothelial and smooth muscle cells.
AB  - Monocrotaline pyrrole (MCTP), a reactive electrophile, induces delayed and
      progressive pulmonary edema, vascular remodeling, and pulmonary hypertension
      after a single intravenous administration to rats. The effects of a single
      exposure of cultured bovine pulmonary artery endothelial cells (BEC) and bovine
      pulmonary artery smooth muscle cells (BSMC) to MCTP were examined. Monocrotaline
      pyrrole caused a dose-dependent, delayed, and progressive cell detachment and
      release of lactate dehydrogenase activity from monolayers of BECs but not BSMCs.
      Monolayers of BECs also released increased concentrations of 6-keto-prostaglandin
      F1 degrees, the stable metabolite of prostacyclin, as the post-treatment interval
      increased. Progressive and marked endothelial cell hypertrophy occurred after
      exposure to a nominal concentration of 5 or 50 micrograms/ml of MCTP but not
      after 0.5 micrograms/ml. Morphologic changes in monolayers of BSMCs were minimal,
      even up to 2 weeks after exposure. Ultrastructurally the hypertrophic, MCTP
      treated BECs had enlarged cell profiles with enlarged nuclei. The nucleoli were
      prominent, occasionally multiple, and had separation of granular and fibrillar
      components. Cytoplasmic microtubules and perinuclear intermediate filaments were
      prominent in some cells, as were the golgi apparatus and endoplasmic reticulum.
      Degenerative changes were not prominent in cells that remained in the monolayer.
      Monocrotaline pyrrole inhibited proliferation of both cell types at
      concentrations (0.5 micrograms/ml) that were not cytotoxic. These findings
      indicate that MCTP induces direct, dose-dependent injury to cells in culture that
      is delayed and progressive, and the expression of this injury depends, in part,
      on the cell type.

PMID- 2000944
TI  - Expression of VLA-alpha 2, VLA-alpha 6, and VLA-beta 1 chains in normal mucosa
      and adenomas of the colon, and in colon carcinomas and their liver metastases.
AB  - 'Very late antigen' (VLA) proteins are members of the integrin superfamily with
      cell-surface receptor function and are involved in the cell-cell matrix
      interaction. They are heterodimers with a common beta 1 chain and different alpha
      chains counted through VLA-1 to VLA-6. The VLA-2 complex (alpha 2/beta 1) was
      found to act as collagen receptor on platelets and the VLA-6 complex (alpha
      6/beta 1) as laminin receptor. Using monoclonal antibodies and an indirect
      immunoperoxidase method, we investigated the expression of VLA-alpha 2, VLA-alpha
      6, and VLA-beta 1 chains in 20 normal colonic mucosa samples, in 20 colonic
      adenomas, and in 96 carcinomas together with 10 accompanying liver metastases.
      All three proteins were expressed throughout the colonic epithelium, except for
      VLA-alpha 2, which was present in the cryptic gland but was absent on the mucosal
      surface in some cases. In general, adenomas were strongly positive for the VLA
      proteins but 3 of 20 cases showed focal VLA-alpha 2-negative areas. The
      carcinomas revealed considerable heterogeneity of VLA-alpha 2 expression; ie, 59
      tumors were completely positive, 35 tumors revealed a focal loss of antigen, and
      2 cases were negative. This reduced antigen expression was statistically
      associated with Dukes' stage C/D (P = 0.003). VLA-alpha 6 was expressed
      throughout in all tumors. VLA-beta 1 was found extensively expressed in 77
      carcinomas, partially expressed in 17 carcinomas, and was absent in 2 carcinomas.
      As compared to their primary tumors, liver metastases showed roughly
      corresponding patterns of antigen expression. The down regulation/loss of VLA
      proteins in a subset of epithelial colon tumors might cause a disturbed cell
      cell/cell-matrix interaction that might augment the invasive property of their
      cells.

PMID- 2000946
TI  - Experimental myelocytic leukemia in the Brown-Norway rat as a model for pulmonary
      leukostasis.

PMID- 2000945
TI  - Cultured human atherosclerotic plaque smooth muscle cells retain transforming
      potential and display enhanced expression of the myc protooncogene.
AB  - The proliferation of vascular smooth muscle cells (SMC) is critical to
      atherosclerotic plaque formation. The monoclonal hypothesis proposes that the
      stimulus for this SMC proliferation is a mutational event. Here we describe a
      procedure for growing human plaque smooth muscle cells (p-SMC) in culture. We
      show that p-SMCs derived from two patients differ from SMC cultured from normal
      vascular tissue in expression of the protooncogene myc. One p-SMC strain was
      extensively characterized; these diploid, karyotypically normal cells have a
      finite life span in culture. Ultrastructural examination revealed two
      populations, one with classic contractile SMC appearance, the other, modulated to
      a synthetic state. Northern blotting showed a 2- to 6-fold and a 6- to 11-fold
      enhanced expression of myc by p-SMC, compared to SMC derived from healthy human
      aorta (HA-SMC) and saphenous vein (HV-SMC), respectively. In contrast, the p-SMC
      and HV-SMC expressed similar levels of message for the genes N-myc, L-myc, Ha
      ras, fos, sis, myb, LDL receptor, EGF receptor, IGF I receptor, IGF II, and HMG
      CoA reductase. Finally, although p-SMCs are not tumorigenic, DNA isolated from
      these cells is positive in the transfection-nude mouse tumor assay. Myc, however,
      does not appear to be the transforming gene because no newly introduced human myc
      gene was detected in the p-SMC-associated nude mouse tumor. Thus human
      atherosclerotic p-SMCs possess both an activated myc gene and a transforming gene
      that is retained throughout many cell passages.

PMID- 2000947
TI  - Structure and function of renal glycosphingolipids.

PMID- 2000948
TI  - Abnormal proximal tubule apical membrane protein composition in X-linked
      hypophosphatemic mice.
AB  - The hypophosphatemic (Hyp) mouse is characterized by an isolated X-linked defect
      in proximal tubular phosphate (Pi) reabsorption associated with a decreased
      maximum velocity (Vmax) and a normal affinity (Km). To directly investigate the
      underlying cellular defect proximal tubular brush-border membranes (BBM) from
      normal control (Con) and Hyp male littermates were examined for differences in
      cholesterol content, total and individual phospholipid composition, phospholipid
      incorporation rates, membrane fluidity, and by two-dimensional sodium dodecyl
      sulfate (SDS)-polyacrylamide protein electrophoresis. The cholesterol content,
      total and individual phospholipid profiles, phospholipid incorporation rates, and
      membrane fluidity of Con and Hyp BBM samples were comparable. However, the two
      dimensional gel electrophoreses of Con and Hyp BBM proteins, run simultaneously
      under identical conditions, revealed a protein with an apparent abnormal
      isoelectric migration pattern in Hyp BBM samples. This protein had an apparent
      molecular weight 56,000 and an apparent pI of 7.2 and was consistently evident on
      Hyp gels (n = 3) but not on Con gels (n = 3). The appearance of this protein band
      was associated with a diminution in staining of a control protein of comparable
      apparent molecular weight but markedly lower apparent pI.

PMID- 2000949
TI  - Sodium transport in salamander proximal tubule at 5.5 degrees C.
AB  - Na+ transport and electrophysiology of isolated perfused proximal tubules of the
      salamander Ambystoma tigrinum were compared at 22 and 5.5 degrees C, a range over
      which these animals normally live. Both intracellular Na+ activity and
      basolateral membrane potential were unaffected by temperature, whereas
      transepithelial potential depolarized from -6.5 +/- 0.8 mV at 22 degrees C to 
      3.5 +/- 0.6 mV at 5.5 degrees C (P less than 0.05). Compared with 22 degrees C,
      reduction of temperature to 5.5 degrees C included major increases in apical
      membrane resistance (2,052 +/- 473 omega.cm2 to 18,464 +/- 2,667 omega.cm2) and
      basolateral membrane resistance (491 +/- 113 omega.cm2 to 1,780 +/- 256
      omega.cm2) (P less than 0.01). Sequential increases of luminal glucose
      concentration allowed characterization of the Na(+) -glucose cotransporter at
      both temperatures. The Km was stable (2 mM), but the maximal activity (Vmax) at
      5.5 degrees C of 167 peq/5 cm2 increased to 1,000 peq/5 cm2 at 22 degrees C (P
      less than 0.05). In parallel with this temperature sensitivity of apical Na+
      entry, basolateral Na+ pump activity was reduced at low temperature. Rubidium
      uptake at 22 degrees C was reduced by 40% at 5.5 degrees C. The rate of decrease
      of intracellular Na+ activity when tubules were perfused with substrate-free
      solution was -2.6 +/- 0.7 mM/min at 5.5 degrees C, compared with -4.9 +/- 1.2
      mM/min at 22 degrees C. We conclude that low temperature reduces both Na+ uptake
      and efflux, allowing stability of intracellular milieu despite reduction in net
      transepithelial transport.

PMID- 2000950
TI  - Increased renal endothelin production in rats with reduced renal mass.
AB  - Renal endothelin (ET) production was investigated in rats after renal mass
      ablation, a model of progressive renal disease characterized by glomerular
      hemodynamic alterations and capillary thrombosis, and in sham-operated animals.
      Thrombin stimulation of renal cortical tissue from rats with renal mass
      reduction, 45 but not 7 days after surgery, generated significantly (P less than
      0.01) more ET than tissue from sham-operated animals. Exposure to thrombin of
      isolated glomeruli from remnant but not sham kidneys also significantly (P less
      than 0.01) increased ET production compared with unstimulated glomeruli. At day
      45, in rats with renal mass ablation ET plasma levels were numerically lower,
      whereas urinary excretion rate of ET was significantly (P less than 0.01)
      increased compared with sham-operated animals. After a 50-min intravenous
      infusion of 125I-ET to normal rats and animals with renal mass ablation, less
      than 0.3% and 0.03%, respectively, of total infused radioactivity was recovered
      in urine. These results indicate that thrombin-stimulated ET production by renal
      cortical tissues is increased in rats with renal mass reduction. Despite normal
      or low-normal plasma ET levels, urinary excretion of the peptide is markedly
      increased in this model. The exogenously labeled ET added to circulation is not
      excreted by the kidney, suggesting that enhanced urinary excretion rate would
      reflect an increased renal production of the peptide in rats with remnant kidney.

PMID- 2000951
TI  - Inhibitory effect of angiotensin II on renal tubular transport.
AB  - This study was designed to examine the intracellular mechanism of inhibitory
      action of high concentration of angiotensin II (ANG II) on proximal tubular
      transport in rat kidneys by microperfusion methods. Perfusion of ANG II (10(-6)
      M) to peritubular capillaries caused a reduction of both fluid and HCO3-
      transport (Jv and JHCO3-, respectively) by 33 and 26%, respectively. These
      inhibitory effects were blocked by the ANG II-receptor antagonist [Sar1, Ile8]ANG
      II (10(-5) M). Similar degrees of inhibition on Jv and JHCO3- were observed when
      ionomycin (10(-7) and 10(-6) M), a Ca2+ ionophore, was added to capillary
      perfusate. Moreover, there was no additive effect when both ANG II and ionomycin
      were perfused together through capillaries, suggesting that both agents work via
      the same mechanism, presumably by increasing cytosolic Ca2+ concentration
      ([Ca2+]i). Inhibitory effects of ANG II on proximal tubular transport were still
      observed in a Ca2(+)-free perfusate containing ethylene glycol-bis(beta
      aminoethyl ether)-N,N,N',N'-tetraacetic acid, indicating that these effects do
      not require influx of Ca2+ from extracellular medium. Furthermore, the
      observation that TMB-8, an agent that prevents intracellular Ca2+ mobilization,
      completely eliminated the effect of ANG II strongly suggests that intracellular
      Ca2+ rather than Ca2+ influx mediates effects of ANG II on proximal tubular
      transport. Direct measurement of [Ca2+]i by use of fura-2 in isolated proximal
      tubular cells showed slight but statistically significant increases in [Ca2+]i.
      Taken together, these observations support the idea that intracellular Ca2+
      serves as a second messenger in the inhibitory effect of high concentrations of
      ANG II on Jv and JHCO3- in proximal tubule of kidney.

PMID- 2000952
TI  - Lymphatic drainage of the peritoneal cavity in sheep.
AB  - Lymphatic drainage of the peritoneal cavity has been investigated in anesthetized
      sheep. Studies involving intraperitoneal administration of a complex of Evans
      blue dye and bovine serum albumin demonstrated the existence of three
      anatomically distinct pathways. In the first pathway, dye is removed from the
      peritoneal cavity by diaphragmatic lymphatics that pass into caudal sternal lymph
      nodes. Efferent lymphatics from these nodes transport the material to cranial
      sternal lymph nodes. Efferent cranial sternal lymphatics then convey the material
      either directly or indirectly, via tracheal lymphatic trunks, to the right lymph
      duct. In the second pathway, the complex is transported from the peritoneal
      cavity by diaphragmatic lymphatics that pass into the caudal mediastinal lymph
      node. Efferent lymphatic ducts from this node transport the material to the
      thoracic duct. The third pathway appears to involve transport of the dye across
      the mesothelial lining of the abdominal viscera and removal from the interstitium
      by afferent visceral lymphatics. Material taken up in this manner is ultimately
      transported to the thoracic duct by efferent visceral lymphatics. Experiments
      involving measurements of lymphatic absorption of 125I-labeled human serum
      albumin from the peritoneal cavity indicated that, over the 6-h period studied,
      4.55 +/- 1.20 and 1.43 +/- 0.56% of the injected tracer could be recovered in
      thoracic duct lymph and caudal mediastinal efferent lymph, respectively, and the
      sum of these values represented 26% of the recovered radioactivity. On the other
      hand, 16.95 +/- 6.93% of the injected radioactivity could be found in the blood
      over the same period.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2000953
TI  - Peptide YY luminal processing and axial heterogeneity of basolateral binding in
      renal proximal tubules.
AB  - This study investigates the definite location of peptide YY (PYY) binding sites
      on the basolateral membranes in proximal tubules. S1, S2, and S3 segments were
      dissected, perfused in vitro, and exposed to [125I-Tyr36]monoiodo-PYY either in
      the bath fluid or in the perfusate. S1 segments exposed to [125I-Tyr36]PYY in the
      bath fluid were fixed and prepared for electron microscope autoradiography. The
      results demonstrated a high degree of axial heterogeneity of basolateral binding
      of PYY, since only S1 bound PYY, 0.59 +/- 0.09 pg/mm after 15 min; 89.1% could be
      displaced with unlabeled PYY. PYY was not internalized, 90% of the grains were
      associated with the basolateral membranes, and no accumulation of grains was
      observed over the vacuolar apparatus. After luminal perfusion with PYY, 79.3 +/-
      7.2% was processed, 61.7 +/- 6.3% was degraded at the brush border, and no
      tubular accumulation was detected. Thus PYY is not taken up by endocytosis.
      Unexpectedly, a very large fraction of processed PYY was transported from lumen
      to bath as trichloroacetic acid (TCA)-precipitable label constituting 41.6 +/-
      4.7%. There was no axial heterogeneity in the luminal handling of PYY. In
      conclusion, this study reveals a high density of PYY binding sites at the
      basolateral membranes from S1 segments, indicating a selective function of S1
      segments on stimulation with PYY. In contrast to other proteins PYY was not
      internalized from the basolateral membranes.

PMID- 2000954
TI  - Three-dimensional anatomy and renal concentrating mechanism. I. Modeling results.
AB  - Simulations were performed to test the hypothesis that the three-dimensional
      organization of the renal medulla is essential for formation of hypertonic urine.
      As in previous models, representations of loops of Henle, distal tubules,
      collecting ducts, and vasa recta and recent estimates of tubule characteristics
      were included in a simulation of NaCl, urea, and fluid transport. In addition,
      this model specifies the relative positions of the medullary structures. By
      assuming that the structure of the minimum functional unit is a vascular bundle
      surrounded by tubules and ascending vessels, we have represented the three
      dimensional organization of the medulla by a cylindrically symmetric two
      dimensional model. The resulting set of equations gives rise to a nonlinear
      boundary value problem with linear boundary conditions, which was solved
      numerically via quasi linearization. Compared with previous simulations, the
      concentrations predicted by this model more accurately match measured quantities
      in two regards. First, papillary tip concentrations of NaCl and urea are
      significantly higher, and, second, a monotonic increase in osmolarity is observed
      in the inner medulla. The three-dimensional organization permitted development of
      local concentration gradients, which are essential to the final result.

PMID- 2000955
TI  - Three-dimensional anatomy and renal concentrating mechanism. II. Sensitivity
      results.
AB  - A mathematical model has been developed to simulate hypertonic urine formation in
      the renal medulla. The model uses published values of membrane transport
      parameters, as have other models, but is unique in its representation of the
      three-dimensional anatomy of the medulla. The model successfully predicts
      measured fluid flows, osmolarities, and NaCl and urea concentrations. The model
      results are presented in the companion to this paper [A. S. Wexler, R. E. Kalaba,
      D. J. Marsh. Am. J. Physiol. 260 (Renal Fluid Electrolyte Physiol. 29): F368
      F383, 1991.]. In this paper we provide tests of the sensitivity of model
      performance to variations in the description of the anatomy and in membrane
      transport parameters. From these studies we conclude that 1) strict counterflow
      arrangements are required in the outer stripe to prevent loss of NaCl to the
      systemic circulation, 2) the radial organization in the inner stripe materially
      improves performance of the inner medulla, 3) radial organization of the inner
      medulla is essential to hypertonic urine formation there, 4) the model is most
      sensitive to variation in collecting duct parameters, and 5) reabsorption of urea
      in the distal tubule improves system performance. The results support the claim
      that the three-dimensional structure, as captured in the model, provides a
      crucial framework for the production of hypertonic urine.

PMID- 2000956
TI  - Reset tubuloglomerular feedback permits and sustains glomerular hyperfunction
      after extensive renal ablation.
AB  - To determine the contribution of the tubuloglomerular feedback (TGF) system to
      glomerular hyperfunction after extensive loss of renal mass, TGF was assessed in
      anesthetized Sprague-Dawley rats 7 days after 5/6 reduction of renal mass (2/3
      infarction of 1 kidney plus contralateral nephrectomy) or sham surgery. Five
      sixths renal ablation significantly increased single-nephron (SN) glomerular
      filtration rate (GFR) 57%, late proximal tubule fluid flow 58-63%, and maximal
      proximal tubule stop-flow pressure (PSF) 24%. Despite these increments, 5/6
      ablation did not increase TGF activation, as judged by the difference between
      proximally and distally measured SNGFR values, nor did it affect maximal TGF
      responses, measured as change in PSF during forward microperfusion of the loop of
      Henle. However, 5/6 ablation increased the late proximal perfusion rate eliciting
      half-maximal PSF suppression (V1/2) from 27.3 +/- 1.6 to 45.7 +/- 2.4 nl/min (P
      less than 0.001), a change closely matching the increment in native late proximal
      tubule fluid flow from 26.6 +/- 2.2 to 43.8 +/- 2.1 nl/min (P less than 0.001).
      Unilateral nephrectomy increased V1/2 less dramatically than did 5/6 ablation,
      thus showing that the effects of renal ablation on TGF are proportional to the
      degree of ablation. We conclude that extensive renal ablation resets TGF
      operation in a way that permits and helps sustain glomerular hyperfunction.

PMID- 2000957
TI  - Relationships between intracellular amino acid levels and protection against
      injury to isolated proximal tubules.
AB  - Metabolism and cellular levels of glycine, alanine, and other relevant amino
      acids in proximal tubules were studied during models of acute injury and
      protection by glycine. Freeze-clamped, normal rabbit renal cortex was very rich
      in glycine (66.8 nmol/mg protein) and glutamate and also had substantial levels
      of taurine, alanine, glutamine, serine, and aspartate. Isolated proximal tubules
      were severely depleted of all these amino acids (glycine, 2.1 nmol/mg protein).
      During 37 degrees C incubation in presence of alanine, tubules recovered only
      glutamate to a level approximating that in vivo (38.8 nmol/mg protein, 15.2 mM).
      Glycine added to medium at levels ranging from 0.25 to 2 mM was actively
      concentrated four- to sixfold by tubule cells. Two millimolar glycine potently
      protected tubules from lethal cell injury induced by hypoxia, antimycin A, or
      ouabain. Glycine levels of injured tubules rapidly equilibrated with medium,
      irrespective of whether glycine was loaded by preincubation or was added
      concomitantly with the injury maneuver. Metabolism of glycine during protection,
      assessed by changes in total levels, gas chromatography-mass spectroscopy
      determination of the fate of [13C]glycine, and redistribution of label from
      [3H]glycine was minimal. The data suggest that glycine plays an essential,
      constitutive role in maintenance of tubule cell structural integrity
      independently of common metabolic pathways. Intracellular amino acid content is
      sufficiently labile for depletion of structurally essential amino acids to
      potentially occur in a variety of settings, but, even with severe ATP depletion
      or Na+ pump inhibition, supplemental glycine is readily available to
      intracellular sites of action.

PMID- 2000958
TI  - Accelerator mass spectrometry: application to study of aluminum kinetics in the
      rat.
AB  - The advent of accelerator mass spectrometry (AMS) now permits the ultrasensitive
      detection of extremely long-lived isotopes, including 14C, 26Al, and 41Ca. Until
      now, tracer studies of aluminum kinetics have not been possible because aluminum
      has only two isotopes, with half-lives of 6.5 min (29Al) and 7 x 10(5) yr (26Al),
      neither of which is suitable for conventional studies. In a novel experiment we
      have employed AMS to study aluminum kinetics in a normal rat and a 5/6
      nephrectomized rat over a 3-wk period of intravenous injection of a tracer dose
      of 26Al. Kinetics were similar in the two animals; approximately 75% of
      intravenously injected tracer 26Al was excreted in the urine in the first 24 h as
      was approximately 80% after 3 wk. Renal clearance of 26Al was approximately 0.75
      ml.min-1.kg body wt-1 in both rats. The results clearly demonstrate the potential
      of this technique for isotope tracer studies in animals as well as in humans.

PMID- 2000959
TI  - Method for studying arterial wave transmission effects on left ventricular
      function.
AB  - A technique for studying the real-time effects of arterial wave reflections on
      the performance of the isolated left ventricle was investigated. Real-time
      arterial loading of an isolated ferret heart with an asymmetric T-tube wave
      transmission model was obtained with the use of a multiprocessor computer control
      system and a volume control linear motor pump. The multiprocessor computer system
      was programmed to compute the instantaneous aortic flow from the instantaneous
      ventricular pressure. The time integral of the flow was used as a command to the
      linear motor pump to control the instantaneous ventricular volume. This loading
      system allowed the imposition of a wide variety of vascular impedances on the
      ventricle by changing the parameters of the asymmetric T-tube model.

PMID- 2000960
TI  - Estimated time course of Ca2+ bound to troponin C during relaxation in isolated
      cardiac muscle.
AB  - We present a mechanical assay for estimating the time course of Ca2+ bound to low
      affinity sites on troponin C (TnC) in twitching rabbit papillary muscle. The
      assay is based on a theoretical correlation between the rate of force
      redevelopment after detachment of all cross-bridges and the amount of Ca2+ bound
      to TnC. Experimentally, we applied length impulses at different times to detach
      all cross-bridges; the initial rate of force redevelopment after each impulse was
      taken as an index of bound Ca2+ at that time. Under control conditions, the
      magnitude of this index decreased to 10% of its maximum during early relaxation,
      when force had declined only slightly 78 +/- 12% of its peak isometric value. The
      time course of this index was examined after addition of either isoproterenol or
      ryanodine, which are known to shorten and prolong, respectively, the
      intracellular free Ca2+ transient. As expected, changes previously reported in
      the free Ca2+ time course were qualitatively reflected in the time course of the
      bound Ca2+ index. We conclude that this index constitutes a reasonable method for
      estimating the time course of bound Ca2+ and that bound Ca2+ declines well ahead
      of force in isometrically contracting rabbit myocardium at 24 degrees C.

PMID- 2000961
TI  - N omega-nitro-L-arginine selectively inhibits vasodilator responses to
      acetylcholine and bradykinin in cats.
AB  - The effects of N omega-nitro-L-arginine (nitroarginine), an inhibitor of
      endothelium-dependent relaxing factor (EDRF) production, on vascular tone and
      responses to vasodilator and vasoconstrictor agents were investigated in the
      hindquarters vascular bed of the cat. Under constant flow conditions, infusion of
      nitroarginine into the hindquarters vascular bed caused a significant increase in
      systemic arterial and hindquarters perfusion pressures. During infusion of
      nitroarginine, hindquarters vasodilator responses to acetylcholine and bradykinin
      were reduced significantly whereas vasodilator responses to isoproterenol, PGE1,
      nitroprusside, and 8-bromoguanosine 3',5'-cyclic monophosphate were not altered.
      Infusion of nitroarginine significantly enhanced vasoconstrictor responses to the
      thromboxane receptor agonist U 46619 and to phenylephrine. The results of these
      studies are consistent with the hypotheses that EDRF production may involve the
      formation of nitric oxide or a nitroso compound from L-arginine, and that EDRF
      production may play a role in the regulation of vascular tone and in the
      mediation of responses to the endothelium-dependent vasodilators, acetylcholine
      and bradykinin, in resistance vessels in the hindquarters. These data support the
      concept that EDRF is very likely an endogenous nitrovasodilator derived from L
      arginine in the hindquarters vascular bed of the cat.

PMID- 2000962
TI  - Nonischemic myocardial damage induced by nonocclusive constriction of coronary
      artery in rats.
AB  - To determine whether reduction in coronary vessel diameter leads to alterations
      in cardiac function, coronary perfusion, and tissue integrity, the left coronary
      artery of rats was narrowed and ventricular hemodynamics measured at 3 and 5 days
      after surgery. Coronary artery narrowing averaged 62% and end-diastolic pressure
      was increased, whereas peak systolic pressure, positive change in pressure over
      time, stroke volume, and total peripheral resistance were decreased. However,
      this impairment of function was accompanied by a preservation of resting coronary
      blood flow (CBF), although a 43% decrease in maximal CBF was detected. Foci of
      reparative fibrosis and myocytolytic necrosis were found primarily in the
      endomyocardium and midmyocardium. These lesions were temporally distinct,
      corresponding to 5 days and 12- to 24-h-old forms of myocardial damage,
      respectively. The changes in maximal CBF correlated with the degree of stenosis,
      whereas the volume fraction, average cross-sectional area, and number of foci of
      reparative fibrosis lesions per unit area of myocardium correlated exclusively
      with end-diastolic pressure. In conclusion, reductions in luminal diameter of a
      major coronary artery not affecting resting coronary perfusion have a profound
      detrimental impact on cardiac performance and initiate immediate myocyte cell
      loss that is ongoing. Thus tissue and cellular damage may not be ischemic in
      nature but rather mediated by other mechanisms such as unbearable mechanical
      stress.

PMID- 2000963
TI  - Diameter changes in arteriolar networks of contracting skeletal muscle.
AB  - The effect of muscular contraction on vessel diameter was studied in the
      arteriolar network of the exteriorized cat sartorius muscle during normal and
      elevated vascular tone. Dilation during 4 Hz motor-nerve stimulation was
      proportionately greatest in the third-order (transverse) arterioles and in
      vessels immediately upstream and downstream (P less than 0.01). This pattern of
      dilation was maintained with increased contraction frequency (30 Hz) and during
      concurrent sympathetic nerve stimulation (8 Hz). The pattern of constriction with
      sympathetic nerve stimulation alone showed a similar trend with the greatest
      response in the third-order and adjacent vessels. A model developed to estimate
      the resistance distribution in the arteriolar network, using data from earlier
      micropressure and vascular architecture studies in the sartorius muscle, allowed
      calculation of the resistance change during muscle contraction and sympathetic
      stimulation. Model predictions indicate that the third-order and adjacent vessels
      are the greatest site of resistance with both normal and elevated vascular tone.
      Thus these vessels were the site of greatest resistance change during muscle
      contraction. The more proximal, arcade vessels made lesser contributions to
      overall resistance changes, whereas the most distal, fifth-, and sixth-order
      arterioles appear not to be important in this regard. These findings indicate the
      third-order, transverse, arterioles are of special importance in regulating blood
      flow in the sartorius muscle.

PMID- 2000964
TI  - Temperature dependence of sodium current block by lidocaine in cardiac Purkinje
      cells.
AB  - Cardiac Na current block by antiarrhythmic drugs has usually been studied at
      lower than physiological temperatures to achieve adequate voltage control, but
      the effect of temperature on block is not well characterized. Using a large
      suction pipette, we studied the effect of 50 microM lidocaine on blocking peak Na
      current between 10 and 25 degrees C in cells isolated from canine cardiac
      Purkinje fibers using three voltage clamp protocols: 1) development of block
      during a prolonged depolarization, 2) recovery from block after a prolonged
      depolarization, and 3) development of block during trains of depolarizations. At
      least two exponential components [a fast component with time constant (tau f) and
      relative amplitude (as) and a slow component with time constant (tau f) and
      relative amplitude (as)] were required to describe both development and recovery
      in lidocaine. For development of block between 10 and 25 degrees C, tau s
      decreased from 1,100 to 200 ms but tau f remained about the same (less than 30
      ms), and as approximately equal to 0.8 and af approximately equal to 0.2 did not
      change with temperature. For recovery between 10 and 25 degrees C, tau a
      decreased from approximately 2,500 to 35 ms, tau f was relatively constant at
      approximately 25 ms, af decreased from 0.46 to 0.16, and as increased from 0.54
      to 0.84. The fractional block developed during pulse trains decreased at higher
      temperatures (from 0.55 at 10 degrees C to 0.22 at 25 degrees C) and developed
      more quickly with time constant 6 pulses at 10 degrees C to 1.3 pulses at 25
      degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2000965
TI  - Loading determinants of isovolumic pressure fall in closed-chest dogs.
AB  - The respective roles of load level and loading sequence of the left ventricle
      (LV) are controversial in the in situ heart. They were analyzed under autonomic
      blockade and sedation in 17 dogs previously instrumented with a pressure
      micromanometer and ultrasonic crystals measuring LV diameters and wall thickness
      for computation of LV volume and stress. The time constant of isovolumic pressure
      fall (T) and end-systolic pressure (ESP) were calculated during the control
      state, caval occlusion, aortic constriction obtained by inflation of a hydraulic
      cuff occluder positioned around the aorta, and during the inflation of an intra
      aortic balloon. Caval occlusion significantly decreased both ESP (from 124.0 +/-
      6.6 to 88.7 +/- 3.7 mmHg; P less than 0.005) and T (from 29.0 +/- 2.2 to 18.8 +/-
      2.4 ms; P less than 0.005), which were linearly correlated (mean r = 0.90 +/-
      0.03) and inflation of an intra-aortic balloon increased both ESP (from 107.3 +/-
      7.1 to 150.6 +/- 10.4 mmHg; P less than 0.005) and T (from 24.6 +/- 2.1 to 32.7
      +/- 2.3 ms; P less than 0.005). Both interventions did not modify the loading
      sequence (analyzed by the evolution of systolic wall stress vs. time). In
      contrast, aortic constriction delayed to midsystole the time to which wall stress
      reached its peak and, for matched ESP with intra-aortic balloon inflation, T was
      not significantly different from control. We conclude that both the level of
      afterload and the loading sequence of LV are the determinants of T when
      contractility is not modified.

PMID- 2000966
TI  - Diastolic stiffness impairs left ventricular function during hypovolemic shock in
      pigs.
AB  - To determine the causes of impaired left ventricular function during hypovolemic
      shock we measured diastolic and end-systolic pressure-volume relationships and
      hemodynamics. Left ventricular pressure (Millar catheter) and volume (3
      ultrasonic crystal pairs) were measured in six open-chest, chloralose-morphine
      anesthetized, juvenile pigs. After baseline measurements, the pigs were bled and
      maintained at a mean aortic pressure of 50 cmH2O for 7 +/- 1 h. After
      resuscitation with all shed blood, left ventricular function was markedly
      impaired as indicated by increased end-diastolic pressure (20.3 vs. 8.7 cmH2O at
      baseline, P less than 0.05), decreased aortic pressure (36% of baseline, P less
      than 0.01), and decreased stroke volume (50% of baseline, P less than 0.01).
      Systolic contractility was increased (P less than 0.05), but diastolic compliance
      was greatly reduced due to decreased diastolic maximum (52% of baseline, P less
      than 0.01) and equilibrium volumes (57% of baseline, P less than 0.01). We
      conclude that impaired left ventricular function during hypovolemic shock is due
      entirely to increased diastolic stiffness. These results can theoretically be
      accounted for by a 20% reduction in myocardial muscle length with no change in
      muscle stress-strain characteristics. This may be the physiological expression of
      morphologically observed myocardial "zonal lesions" of hypovolemic shock.

PMID- 2000967
TI  - Activity of in vivo atrial and ventricular neurons in chronically decentralized
      canine hearts.
AB  - The spontaneous activity of 175 neurons located in the ventral right atrial and
      ventral interventricular ganglionated plexi was recorded in eight anesthetized
      dogs, the hearts of which were chronically decentralized at least 2 wk before
      recordings were made. Ganglia were subsequently identified anatomically in the
      immediate vicinity of the recording sites. Spontaneous activity was correlated
      with the cardiac cycle in 57% of the atrial and 62% of the ventricular neurons
      and with the respiratory cycle in 29% of the atrial and 28% of the ventricular
      neurons. Spontaneous cardiovascular-related activity was recorded when systemic
      arterial pressure was between 80 and 175 mmHg. The activity of 23 atrial and 15
      ventricular neurons was altered when discrete regions of the heart were
      mechanically distorted by gentle touch. These data imply that cardiac
      ganglionated plexi contain afferent neurons that receive inputs from limited
      regions of the heart. The spontaneous activity generated by intracardiac neurons
      was not altered when extracardiac tissues were distorted. These results
      demonstrate that neurons in ganglia on chronically decentralized hearts can
      generate spontaneous activity, a large fraction of which is correlated with
      cardiovascular or respiratory events.

PMID- 2000968
TI  - Inhibition of cardiac vagal component of baroreflex by group III and IV
      afferents.
AB  - The action of electrically evoked activity in somatic afferent fibers on the
      sensitivity of the baroreceptor reflex was examined in decerebrate cats. The
      sensitivity of the reflex was expressed as the difference between the maximum
      prolongation of R-R interval in response to carotid sinus pressure elevation and
      the mean of 10 R-R intervals immediately before pressure elevation. The control
      value of R-R interval prolongation was 192 +/- 50 ms. Stimulation (10 Hz) of
      group I and II fibers of the right peroneal nerve (evoked volleys recorded from
      the sciatic nerve) had no effect on R-R interval prolongation (171 +/- 45 ms).
      Recruitment of group III fibers (10 Hz) conducting at 23.6 +/- 0.65 m/s reduced
      the prolongation of R-R interval to 52 +/- 14 ms. Recruitment of group IV fibers
      (10 Hz) conducting less than 2.5 m/s further reduced the prolongation of R-R
      interval to 1.0 +/- 8.0 ms. It is concluded that the inhibition of the cardiac
      vagal component of the baroreceptor reflex produced by electrical stimulation of
      the peroneal nerve is mediated by afferent fibers of groups III and IV.

PMID- 2000969
TI  - Removal of sialic acid alters both T- and L-type calcium currents in cardiac
      myocytes.
AB  - The whole cell configuration of the patch-clamp technique was used to test the
      hypothesis that the presence of sialic acid residues influences both T- and L
      type Ca2+ currents (ICa,T and ICa,L) in cultured pacemaker cells isolated from
      the rabbit sinoatrial node. Removal of these anionic sugar moieties by
      neuraminidase (1.0 U/ml for 5-20 min) increased ICa,T in five of nine cells (by a
      factor of 2.2-5.1) and ICa,L in three of six cells (by a factor of 1.2-1.6). In
      cells that did not exhibit such an increase, the enzyme reduced ICa,T but had no
      significant effect on ICa,L. In cells that exhibited an increase in ICa,T,
      exposure to neuraminidase also shifted the activation curve to more negative
      potentials and increased the slope of the inactivation curve. The enzyme did not
      influence the gating of ICa,L or the rates of inactivation of either ICa,T or
      ICa,L. The enhancement of ICa,T and ICa,L could not be mimicked by including
      neuraminidase in the patch pipette or by adding a contaminant of the enzyme
      preparation, phospholipase C, to the bath. When external Ca2+ was replaced by
      Ba2+, neither ICa,T nor ICa,L was increased significantly by neuraminidase. It is
      proposed that by removing sialic acid residues neuraminidase might directly alter
      the gating of T-type Ca2+ channels. On the other hand, the increased amplitudes
      of ICa,T and ICa,L might be due to a rise in intracellular Ca2+.

PMID- 2000970
TI  - Left ventricular contractility is depressed in IgE-mediated anaphylactic shock in
      dogs.
AB  - To determine whether myocardial dysfunction contributes to vascular collapse in
      anaphylactic shock, we examined left ventricular (LV) contractility, coronary
      blood flow, and myocardial lactate metabolism during antigen challenge in eight
      dogs that were sensitized to ragweed pollen extract (anaphylaxis group). Findings
      in the anaphylaxis group were contrasted to those in another group of dogs in
      which mean blood pressure was decreased to the same extent by arteriolar
      vasodilation with nitroprusside. The animals were examined under nonhypoxic
      conditions while anesthetized and ventilated. LV mechanics were examined with
      subendocardial crystals placed primarily along the anterior-posterior minor axis
      of the LV. During antigen challenge, a depression in LV contractility was
      observed in the anaphylaxis group as assessed by fractional dimensional
      shortening, stroke volume, and the slope of the end-systolic pressure-dimension
      relationship. During anaphylaxis, moreover, coronary vasodilation rather than
      coronary vasoconstriction was observed, and evidence of myocardial ischemia as
      assessed by altered myocardial lactate metabolism was not found. Our results
      indicate that depressed LV contractility occurs in anaphylactic shock. The
      results further suggest that the mechanism may be due to a direct effect of
      mediators of anaphylaxis on the myocardium to produce systolic dysfunction.

PMID- 2000971
TI  - Carotid sinus baroreceptor reflex control of venular pressure-diameter relations
      in rat intestine.
AB  - We tested the hypothesis that the venules of the small intestinal muscle are
      responsible for decreases in vascular capacitance during bilateral carotid artery
      occlusion. We measured microvascular venular pressure and diameter relations in
      135 vessels during both control and baroreflexive conditions (bilateral carotid
      occlusion). Microvascular pressure was measured using a servo-null pressure
      system, and diameters were obtained from a video-monitoring system with a total
      magnification of X1,000. First-, second-, and fourth-order microvenules were
      studied in rat small intestinal muscle. The vessels showed an average diameter
      decrease of 11-12% and an increased stiffness or pressure-diameter slope of 31
      53% during bilateral occlusion. We also tested whether the observed constriction
      during bilateral occlusion was caused by an increase in the sympathetic nerve
      activity to the venules and/or increased hormonal release via the baroreflex
      system. We studied an additional 22 microvenules before and after denervation of
      the preparation. Denervation eliminated any significant change in diameter or
      stiffness during bilateral occlusion. Based on our data, we conclude that the
      changes in the venular properties observed during bilateral occlusion are due to
      the increased sympathetic nerve activity resulting from decreased carotid sinus
      pressure. Intestinal venules can actively constrict to change vascular
      capacitance during bilateral carotid occlusion.

PMID- 2000972
TI  - Influence of brain renin-angiotensin system on renal sympathetic and cardiac
      baroreflexes in conscious rabbits.
AB  - The role of the brain renin-angiotensin system (RAS) in the baroreflex regulation
      of renal sympathetic nerve activity (RSNA) and heart rate (HR) was studied in
      conscious rabbits. RSNA and HR were recorded during slow ramp changes in mean
      arterial pressure (MAP) before and after intraventricular infusion of 1)
      angiotensin II (ANG II), 2) ANG II receptor antagonist, [Sar1,Ile8]ANG II, or 3)
      converting enzyme inhibitor (CEI, enalaprilat). Central ANG II increased resting
      MAP and RSNA by 10.6 +/- 0.9 mmHg and 21 +/- 7%, respectively, but did not alter
      HR. There was a marked increase of 107 +/- 15% in the maximum RSNA evoked by
      slowly lowering MAP. In contrast, maximum reflex tachycardia was only modestly
      elevated, and baroreflex inhibition of RSNA and HR during MAP rises was
      unaffected. Central [Sar1,Ile8]ANG II had no effect on RSNA or HR, either at rest
      or during baroreflex responses, while CEI slightly enhanced maximal reflex
      responses. Thus exogenous ANG II causes a powerful excitation of renal
      sympathetic motoneurons, the magnitude of which is revealed when tonic
      baroreceptor inhibition is removed during transient pressure falls. However, in
      quietly resting conscious rabbits, we found no evidence for a tonic influence of
      endogenous ANG II on these neurons, and the physiological stimuli required for
      their activation by the brain RAS remain to be found.

PMID- 2000973
TI  - Myogenic response of isolated pressurized rabbit ear artery is independent of
      endothelium.
AB  - Central ear artery segments, removed from urethan-anesthetized rabbits, were used
      to assess whether distention activation was dependent on intact and functional
      endothelium (ENDO). Changes in external arterial diameter were measured with
      light-dependent diode array mounted above the vessel. After constriction with
      norepinephrine, slow increases in pressure from 60 to 80 or 100 mmHg performed
      over 120 s (pressure ramps) failed to initiate distention, but initial diameter
      was maintained. Rapidly applied (500 ms) pressure increases (pressure jumps)
      across same pressure ranges gave rise to initial distention and a myogenic
      response resulting in a return to almost initial diameter while new pressure was
      maintained for 120 s. Myogenic activity was measured from extent of recovery of
      vessel to its initial diameter during maintenance of pressure jumps or ramps.
      Rapid jumps and slow ramps were performed in presence of an intact ENDO and again
      after ENDO was removed by passage of intraluminal gas. With pressure jumps 60 to
      80 mmHg, degree of recovery in ENDO-denuded vessels was 91.9% compared with 89.5%
      in ENDO intact vessels. For pressure jumps 60 to 100 mmHg, extent of recovery was
      87.4 and 89.6%. During application of pressure ramps of 20 or 40 mmHg, vessel
      diameter did not increase by greater than 5%. There are no significant
      differences in these data, and we conclude that myogenic response in rabbit ear
      artery is mediated independently of endothelial-derived factors, irrespective of
      whether myogenic activation is induced by pressure jumps or ramps.

PMID- 2000974
TI  - Myocardial protection is lost before contractile function recovers from ischemic
      preconditioning.
AB  - Preconditioning myocardium with brief episodes of ischemia reduces energy demand
      and delays cell death during a subsequent ischemic episode. We hypothesized that
      postischemic contractile dysfunction after the brief ischemic episodes
      ("stunning") causes this reduced energy demand. If this hypothesis is correct,
      then cardioprotection should persist as long as mechanical function still is
      depressed at the onset of sustained ischemia. To analyze the temporal
      relationship between preconditioning and stunning, infarct size was compared in
      two groups of open-chest anesthetized dogs that were preconditioned with a 15-min
      coronary occlusion followed by a sustained 40-min occlusion. One group received 5
      min of reperfusion and the second group received 120 min of reperfusion between
      occlusions. Nonpreconditioned controls received a single 40-min occlusion. A 15
      min occlusion caused severe stunning, which did not improve during 2 h of
      reperfusion. In the 5-min reflow group, preconditioning resulted in dramatically
      smaller infarcts, averaging 2.2 +/- 0.9% of the area at risk vs. 26.5 +/- 4.2% in
      controls (P less than 0.01), confirmed by a marked shift in the inverse
      relationship between collateral blood flow and infarct size. Despite persistently
      severe stunning in the 120-min reflow group, infarct size was intermediate,
      averaging 12.3 +/- 2.7% (P less than 0.05 vs. 5-min reflow; P less than 0.01 vs.
      control), and the infarct vs. flow regression had returned toward control. Thus
      the cardioprotective effect of preconditioning was attenuated when the
      intervening reperfusion time was extended, even though severe contractile
      dysfunction persisted. We conclude that myocardial stunning, per se, is
      insufficient to cause preconditioning.

PMID- 2000975
TI  - Existence and participation of xanthine oxidase in reperfusion injury of ischemic
      rabbit myocardium.
AB  - Using a highly specific assay that minimizes enzyme inactivation in vitro, we
      found that rabbit myocardial tissue contained low levels of xanthine oxidase (XO)
      and xanthine dehydrogenase (XD) activity that were effectively inhibited by
      pretreatment of hearts with allopurinol. In parallel, allopurinol treatment also
      improved ventricular developed pressure, peak systolic pressure, and coronary
      flow in isolated hearts subjected to 30 min of normothermic global ischemia and
      30 min of reperfusion. Although function was protected by allopurinol treatment,
      creatine kinase (CK) release was not altered by allopurinol. Inhibition of
      myocardial XO with allopurinol did not increase myocardial ATP or
      phosphocreatine. In addition, allopurinol did not scavenge superoxide anion or
      hydrogen peroxide in vitro. The results support the possibility that relatively
      low amounts of XO activity, similar to levels reported in human myocardium, may
      contribute to cardiac ischemia-reperfusion injury.

PMID- 2000976
TI  - Contrasting effects of vasopressin and angiotensin II on rabbit aortic
      baroreceptors.
AB  - Arginine vasopressin (AVP) reportedly enhances, whereas angiotensin II (ANG II)
      attenuates, baroreflex control of the circulation. Here we examine whether these
      responses can be attributed, in part, to local actions on myelinated baroreceptor
      (BR) afferents, either directly or via changes in vascular tone. An in vitro
      rabbit aortic arch/aortic nerve preparation was used to study regularly
      discharging presumably myelinated BRs under controlled static and pulsatile
      pressures. At constant suprathreshold pressures, AVP (10(-13) M to 10(-6) M) had
      no effect on arch diameter or BR frequency, whereas equimolar concentrations of
      ANG II evoked dose-dependent vasoconstriction and associated BR inhibition.
      Differences were not caused by limited diffusion to BR endings lying outside the
      media, since similar results were obtained with either luminal or adventitial
      applications. AVP also had no effect on diameter or discharge in arches
      preconstricted with norepinephrine, whereas acetylcholine (ACh) relaxed the arch
      and thereby increased BR activity. These results eliminate possible AVP-induced
      endothelium-dependent vasodilation or potentiation of adrenergic vasoconstriction
      that would not be evident in isolated arches lacking tone. Finally, AVP did not
      sensitize BRs to changes in pressure, since ramp-evoked pressure-discharge curves
      remained constant and pulsatile discharge in response to sine-wave pressure
      inputs was unaltered. ANG II, however, shifted pressure-discharge curves to
      higher pressures and, with pulsatile inputs at constant mean pressure, reduced
      peak and average discharge firing rates. In conclusion, AVP has no apparent
      peripheral effect on aortic myelinated BRs in rabbits that could contribute to
      amplification of the baroreflex when AVP levels are elevated. In contrast, ANG II
      can inhibit BR firing as a consequence of local vasoconstriction, which may
      contribute to attenuation of the reflex when ANG II levels are elevated.

PMID- 2000977
TI  - Effect of adrenalectomy or sympathectomy on spinal cord blood flow in hypothermic
      rats.
AB  - We used [14C]butanol distribution to measure regional spinal cord blood flow
      (RSCBF) in three groups of pentobarbital-anesthetized rats: 1) normals (n = 16);
      2) after bilateral adrenalectomy (n = 18); and 3) after excision of the abdominal
      sympathetic chains (n = 12). Half of the rats in each group were maintained near
      normothermia; the remainder were colled to a rectal temperature of 25-27 degrees
      C. In intact rats, there was a 24-37% increase in RSCBF during hypothermia in the
      cord region C3-L6 inclusive. Neither operative procedure altered RSCBF during
      normothermia. In hypothermic adrenalectomized rats, RSCBF was elevated only in
      the C3-C5 cord segment. After sympathectomy, RSCBF was unchanged during
      hypothermia. In the cauda equina, flow fell in all hypothermic rats. The
      hypothermia-associated increases in RSCBF were not related to changes in mean
      arterial blood pressure. We conclude that adrenalectomy near-totally ablates the
      hypothermia-associated increase in RSCBF measured in intact rats and that
      abdominal sympathectomy totally ablates it. This evidence complements
      morphological evidence for adrenergic innervation of the spinal cord vasculature.

PMID- 2000979
TI  - Power spectral analysis of blood pressure variability in traumatic quadriplegic
      humans.
AB  - A study was performed on seven traumatic neurologically complete quadriplegic
      (QP) males and seven age-matched healthy males (control) while they were at rest
      in the supine position in a climatic chamber (temperature 30 degrees C, relative
      humidity 60%). Arterial blood pressure waveforms were measured by a continuous
      noninvasive blood pressure-monitoring system based on arterial tonometry.
      Furthermore, the spontaneous beat-to-beat systolic blood pressure (SBP)
      variabilities of subjects were investigated by means of autoregressive power
      spectral analysis. As shown by earlier studies with an invasive (intra-arterial)
      blood pressure-monitoring system, in the control group there were two major
      spectral components: a high-frequency (HF) component [center frequency 0.27 +/-
      0.02 (SE) Hz eq, power 0.9 +/- 0.2 mmHg2] and a low-frequency (LF) component
      (0.10 +/- 0.01 Hz eq, 5.2 +/- 1.4 mmHg2). On the contrary, in the QP group only
      the HF component was observed (0.28 +/- 0.03 Hz eq, 3.2 +/- 1.4 mmHg2). The
      results suggest that 1) in the QP subject the disappearance of the LF component
      in the SBP variability (i.e., the Mayer waves in humans) is presumably caused by
      the interruption of the spinal pathways linking supraspinal cardiovascular
      centers with the peripheral sympathetic outflow and 2) the cervical spinal
      sympathetic pathways may be instrumental in the genesis of the Mayer waves in
      humans.

PMID- 2000978
TI  - Coronary vascular smooth muscle function in E. coli endotoxemia in dogs.
AB  - The purpose of this study was to determine whether intrinsic contraction
      relaxation properties of coronary arteries are altered during acute gram-negative
      endotoxemia. Coronary vascular smooth muscle (VSM) was evaluated in vitro using
      large and small left circumflex coronary ring preparations isolated from dogs 4 h
      after administration of either saline (control; C) or 1.5 mg/kg Escherichia coli
      endotoxin (ET). ET dogs exhibited marked systemic hypotension and cardiovascular
      depression throughout the 4-h in vivo phase of the study accompanied by reduction
      in total left ventricular myocardial blood flow. Isolated coronary vessels were
      stretched to the apex of the length-contractile tension curve; no differences
      were observed in length-active or length-passive tension (vessel compliance)
      relationships between C and ET vessels. Isometric contractions produced by K+ and
      prostaglandin F2 alpha (PGF2 alpha) were similar in C and ET coronary arteries.
      VSM relaxant responses to nitroprusside (NP; 10(-10) to 10(-4) M) were also
      similar in C and ET vessels. In contrast to the apparent lack of effect of ET on
      directly acting VSM agents, relaxation responses to the endothelial-dependent
      vasodilator acetylcholine (ACh) were significantly less in ET vessels. Impaired
      vasodilator response to ACh was not improved by in vivo treatment with the
      combination antioxidant therapy of allopurinol, superoxide dismutase, and
      catalase. We conclude that both depolarization (K+) and receptor (PGF2 alpha)
      mediated contractile mechanisms, as well as basal cGMP (NP)-mediated vasodilator
      mechanisms, remained functional in coronary vasculature during acute endotoxemia.
      Inhibition of ACh-mediated relaxation in ET vessels suggests altered endothelial
      dependent vasodilation in coronary arteries during endotoxemia, but this change
      did not seem to be associated causally with oxygen free radicals.

PMID- 2000980
TI  - Endothelial regulation of wall shear stress and blood flow in skeletal muscle
      microcirculation.
AB  - In the presence of intact endothelium, in control conditions, calculated wall
      shear rate (WSR) (means +/- SE: 2,658 +/- 123 s-1; n = 21) was independent of
      arteriolar diameter (16.2-27.2 microns; correlation coefficient: r = 0.12, P
      greater than 0.05) in cremaster muscle of pentobarbital-anesthetized rats. An
      increase in blood flow velocity (due to parallel arteriolar occlusion) elicited a
      significant increase in WSR (to 4,981 +/- 253 s-1) followed by a delayed (6-15 s)
      increase in diameter (from: 22.5 +/- 0.6 to 29.5 +/- 0.8 microns), which
      consequently resulted in a significant decrease in WSR (to 3,879 +/- 203 s-1). As
      a result of the increased flow velocity and dilation, calculated arteriolar blood
      flow increased by 230%. After impairment of the endothelium of arterioles by a
      light-dye technique, basal WSR became significantly higher (3,604 +/- 341 s-1),
      and despite a greater increase in WSR (10,360 +/- 1,471 s-1) the dilation was
      absent. Now an inverse linear correlation was found between arteriolar diameter
      and WSR both before (r = 0.58, P less than 0.05) and during increased flow
      velocity conditions (r = 0.85, P less than 0.05). Also, arteriolar blood flow
      that was already less after impairment of endothelium increased by only 66%
      during the period of increased flow velocity due to the absence of dilation.
      Results suggest that an increase in wall shear stress is the stimulus for the
      endothelium-dependent mechanism that elicits "flow dependent" arteriolar
      dilation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2000981
TI  - A cardiodepressant factor isolated from blood blocks Ca2+ current in
      cardiomyocytes.
AB  - A cardiodepressant factor (CDF) was isolated (salt free) from the plasma of dogs
      after hypovolemic-traumatic shock by column chromatography. CDF was found to
      exert a concentration-dependent negative inotropic effect in guinea pig papillary
      muscle; it reduced the amplitude of cell wall motion, the contraction and
      relaxation velocity, and the frequency of spontaneously beating rat
      cardiomyocytes in culture, effects that were rapidly reversible upon washout. By
      means of electrophysiological methods (whole cell recording with patch electrodes
      and voltage clamp) we tested the effect of CDF on adult guinea pig
      cardiomyocytes: application of CDF initially decreased the plateau by 7 mV (150
      ms after peak of action potential) and reduced the action potential duration by
      93 ms (76% of control action potential duration) at 50% and 88 ms (79%) at 90% of
      repolarization. The plateau was further reduced by 13 mV and the action potential
      duration was prolonged by 25 ms (106%) at 50% and was prolonged drastically by
      156 ms (137%) at 90% of repolarization compared with control. Voltage-clamp
      experiments have shown that the most prominent effect of CDF is a strong
      reduction of ICa accompanied by inhibition of IK and subsequent repolarization.
      Similar results have been obtained with neonatal rat cardiomyocytes. Blockage of
      the calcium inward current can explain the negative inotropic and chronotropic
      effect of CDF in cardiomyocytes.

PMID- 2000982
TI  - Role of phospholipases A2 and C in myocardial ischemic reperfusion injury.
AB  - We investigated the role of phospholipase A2 (PLA2) and phospholipase C (PLC) in
      myocardial phosholipid degradation and cellular injury during reperfusion of
      ischemic myocardium. For this purpose, isolated rat hearts were perfused with
      isotopic arachidonic acid to label its membrane phospholipids. Hearts preperfused
      with antiphospholipase A2 (anti-PLA2) retained a significantly higher amount of
      radiolabel in phosphatidylcholine and phosphatidylinositol and a corresponding
      lower amount of radiolabel in lysophosphatidylcholine and nonesterified fatty
      acids (P less than 0.05) after 30 min of reperfusion following 30 min of
      normothermic global ischemia compared with hearts preperfused with nonimmune
      immunoglobulin G. In similar experiments, antiphospholipase C (anti-PLC)-treated
      hearts were associated with significantly (P less than 0.05) higher radiolabel in
      all phospholipids and lower radiolabel in diacyglycerol compared with nonimmune
      immunoglobulin G-treated hearts. Measurement of phospholipase activity in
      subcellular organelles of these hearts showed decreased PLA2 activity in cytosol,
      mitochondria, and microsomes of anti-PLA2-treated hearts and decreased PLC
      activity of microsomes in anti-PLC-treated hearts. Furthermore, both the
      antiphospholipases attenuated the release of creatine kinase and lactate
      dehydrogenase into perfusate and increased contractility as well as coronary flow
      in the reperfused hearts. Results of this study suggest that both PLA2 and PLC
      are involved in the degradation of phospholipids and cellular injury that occur
      during reperfusion of ischemic myocardium.

PMID- 2000983
TI  - Mechanisms of rate staircase in rat ventricular cells.
AB  - We studied the steady-state rate staircase in isolated rat ventricular cells
      stimulated at frequencies ranging up to 6 Hz at 37 degrees C. When contractility
      was measured as displacement of the cell edge, amplitude of motion decreased
      while stimulation rates were increased from rest to 1 Hz (negative staircase).
      With further increases in the rate of stimulation to 6 Hz, amplitude of motion
      increased for each increment in stimulation rate (positive staircase). Ryanodine
      at a concentration of 100 nM was a negative inotrope and abolished the rested
      state contraction and the negative staircase seen between rest and 1 Hz (P less
      than 0.05) but had no significant effect on twitch amplitude or the staircase at
      stimulation rates between 1 and 6 Hz. L-type Ca2+ channel inhibition with
      verapamil (0.2 microM) had little effect on twitch or the negative staircase from
      rest to 1 Hz, but twitch amplitude was diminished and the staircase was converted
      from positive to negative at stimulation rates between 1 and 6 Hz (P less than
      0.05). We conclude that in rat ventricular cells studied at 37 degrees C, the
      rate staircase is biphasic: negative from rest to 1 Hz and positive from 1 to 6
      Hz. This phenomenon is dominated by Ca2+ release from the sarcoplasmic reticulum
      at rates less than 1 Hz and by Ca2+ entry through L channels at rates greater
      than 1 Hz.

PMID- 2000984
TI  - Influence of low perfusion pressure on effect of endothelin on coronary vascular
      bed.
AB  - The goal of this study was to evaluate the influence of low coronary perfusion
      pressure on the coronary vasoconstriction induced by endothelin. For this
      purpose, the circumflex coronary arteries of 12 open-chest dogs were cannulated
      and perfused at a controlled pressure. Total coronary blood flow was measured
      with an electromagnetic flowmeter and the transmural distribution of coronary
      blood flow with the radioactive microspheres technique. In addition, the
      circumflex coronary artery diameter was measured by sonomicrometry with
      piezoelectric crystals, and the coronary cross-sectional area was calculated. At
      a coronary perfusion pressure of 100 mmHg, endothelin induced a marked coronary
      vasoconstriction and a redistribution of coronary blood flow toward the
      endocardium. At a low coronary perfusion pressure of 40 mmHg, these effects of
      endothelin were still present. The constriction of the large coronary artery
      occurred even with a lower dose of endothelin at a low coronary perfusion
      pressure compared with the normal perfusion pressure. This was not the case when
      angiotensin II was given the same way. We conclude that endothelin is a potent
      coronary vasoconstrictor even at a low perfusion pressure. Thus one may speculate
      that endothelin plays a role in the coronary spasm which has been shown in
      patients with angina pectoris.

PMID- 2000986
TI  - Myocardial adrenergic changes at two stages of heart failure due to adriamycin
      treatment in rats.
AB  - Changes in myocardial norepinephrine (NE) levels, turnover, uptake, and release
      in rats were examined at two stages of cardiac dysfunction induced by adriamycin
      (ADR) given intraperitoneally in six equal doses over a period of 2 wk for a
      cumulative dose of 15 mg/kg. At 3 wk posttreatment, ADR-treated animals showed no
      changes in left ventricular systolic pressure (LVSP), aortic systolic pressure
      (ASP), and aortic diastolic pressure (ADP) but left ventricular end-diastolic
      pressure (LVEDP) was significantly higher. At 6 wk posttreatment, LVSP, ASP, and
      ADP were significantly lower and LVEDP remained elevated. Animals in both ADR
      treated groups showed signs of congestive heart failure as indicated by ascites,
      congestive liver, and elevated LVEDP. Structural changes typical of ADR
      cardiomyopathy were more pronounced in the 6-wk group. In vivo hemodynamic as
      well as in vitro muscle function response to different concentrations of
      epinephrine was depressed in its duration as well as extent in both 3- and 6-wk
      ADR-treated groups. Myocardial NE levels were increased in the 3-wk group but
      were depressed in the 6-wk group. NE turnover was faster in both 3- and 6-wk ADR
      groups, uptake was increased only in the 6-wk group, and release was unchanged.
      These data show increased cardiac sympathetic tone at both stages of ADR-induced
      congestive heart failure.

PMID- 2000985
TI  - Stimulation of area postrema decreases blood flow to choroid plexus.
AB  - The goal of this study was to examine effects of stimulation of the area postrema
      on blood flow to choroid plexus and brain. In chloralose-anesthetized dogs, the
      area postrema was stimulated electrically, and arterial pressure and blood gases
      were maintained at control levels. We measured blood flow to brain and choroid
      plexus of the fourth and lateral ventricles with microspheres. Stimulation of the
      area postrema at 10 +/- 2 microA (means +/- SE), which was the threshold for
      changes in arterial pressure and heart rate, decreased blood flow to choroid
      plexus of the fourth and lateral ventricles by 41 +/- 11 and 51 +/- 6%,
      respectively (from 349 +/- 38 and 503 +/- 46 ml.min-1.100 g-1, respectively).
      Stimulation at high amplitudes (67 +/- 5 microA) produced only slightly greater
      decreases in blood flow to choroid plexus. In contrast, cerebral blood flow did
      not change during stimulation of the area postrema. After blockade of autonomic
      ganglia with intravenous chlorisondamine, stimulation of the area postrema had
      minimal effects on blood flow to choroid plexus. The results indicate that
      stimulation of the area postrema decreases blood flow to choroid plexus, probably
      by an autonomic mechanism. We speculate that the area postrema may play a role in
      regulation of volume in the central nervous system by modulating production of
      cerebrospinal fluid.

PMID- 2000987
TI  - Adenosine formation and energy status during hypoperfusion and 2-deoxyglucose
      infusion.
AB  - The relationship between adenosine (Ado) formation and cytosolic energy status
      was studied in isolated guinea pig hearts during hypoperfusion plus
      norepinephrine infusion (0.6 nmol/min) and in isolated rat hearts during 2
      deoxyglucose (2-DG) infusion. 31P nuclear magnetic resonance (31P-NMR) was used
      to measure phosphate concentrations, and both phosphorylation potential
      (expressed as [ATP]/[ADP][Pi]) and energy charge [expressed as (([ATP] +
      1/2[ADP])/([ATP] + [ADP] + [AMP]))] were calculated as indexes of cytosolic
      energy status. Both progressive flow reductions and increasing length of exposure
      to 2-DG led to progressive decreases in energy charge and phosphorylation
      potential. In both cases, steady-state Ado release first increased then declined
      despite a continued fall in energy status. Inosine release followed a similar
      pattern. This biphasic pattern of Ado release vs. energy charge is similar to the
      pattern seen in in vitro studies of cytosolic 5'-nucleotidase, supporting the
      hypothesis that Ado formation in vivo is regulated by the influence of energy
      status on this enzyme. However, Ado release in vivo peaked at an energy charge
      much higher (0.997) than that observed in vitro (0.60-0.86). It is therefore
      probable that the inhibition of Ado formation in the perfused heart occurs via
      factor(s) in addition to energy charge.

PMID- 2000988
TI  - Decreased transient outward K+ current in ventricular myocytes from acromegalic
      rats.
AB  - Cardiac hypertrophy and heart failure are common to acromegalic patients who have
      abnormally high serum growth hormone (GH). While the function of cardiac muscle
      is clearly affected by chronically elevated GH, the electrical activity of
      myocytes from hearts with GH-dependent hypertrophy has not been studied. We used
      adult, female Wistar-Furth rats with induced GH-secreting tumors to study the
      effect of excessive GH on ion channels of cardiac myocytes. GH-secreting tumors
      were induced by subcutaneous inoculation of GH3 cells. Eight weeks after
      inoculation, the rats had doubled their body weight and heart size compared with
      age-matched controls. There were no differences in either action potential
      amplitude or resting potential of right ventricular myocytes from control and
      tumor-bearing rats. However, action potential duration increased significantly in
      tumor-bearing rats; the time to 50% repolarization was 23 +/- 14 ms (n = 10)
      compared with 6.6 +/- 1.5 ms (n = 14) in controls. The prolongation of the action
      potential was mainly due to a decrease in density of a transient outward current
      (It,o) carried by K+. The normalized conductance for It,o decreased from 0.53 +/-
      0.10 nS/pF (n = 25) in controls to 0.33 +/- 0.09 nS/pF (n = 26) in tumor-bearing
      rats. The decrease in It,o) and increase in heart weight occurred with a similar
      time course. The increased action potential duration prolongs Ca2+ influx through
      L-type Ca2+ channels in the tumor-bearing animals; this may be important in
      cardiovascular adaptation.

PMID- 2000989
TI  - Diastolic coronary resistance and capacitance are independent of the duration of
      diastole.
AB  - Systolic myocardial contraction may produce changes in coronary resistance and
      capacitance that persist throughout a normal diastole. In addition, coronary
      resistance and capacitance as determined in the arrested heart may not accurately
      describe normal diastolic behavior. To evaluate these possibilities, an
      identification method capable of characterizing the input impedance of the
      coronary circulation in as little as 150 ms was developed. Using this method,
      coronary dynamics were measured during early and late diastoles in the beating
      heart with tone intact as well as during adenosine-induced maximal vasodilation.
      Coronary dynamics were also measured in the arrested heart during maximal
      vasodilation. With vasomotor tone intact, the parameters of a lumped model of the
      coronary circulation showed no variation from early to late diastole. During
      maximal vasodilation, model parameters also showed no variation from early to
      late diastole. Parameters in the arrested heart were not statistically different
      from those of the beating heart during maximal vasodilation. However, model
      parameters determined during maximal vasodilation were significantly different
      from those determined with tone intact. These results suggest that although
      coronary resistance and capacitance are dependent on vasomotor tone, they remain
      constant throughout diastole and remain similar in the arrested heart.

PMID- 2000990
TI  - Right and left atrial diameters during incremental atrial pacing in pigs.
AB  - The relationship between right and left atrial diameters and heart rate was
      examined in 14 open-chest barbiturate-anesthetized pigs by an ultrasonic
      technique. The maximal atrial diameter was read at the top of the v wave, which
      decreased in both atria when heart rate was increased from 124 (118-130) to 159
      (156-160) (median and 95% confidence interval) beats/min. Right and left atrial
      maximal diameter fell significantly from 25.7 (23.6-32.6) to 24.9 (22.9-29.5) mm
      and from 30.8 (25.1-37.2) to 29.8 (23.4-36.3) mm, respectively, when heart rate
      was increased from 124 to 180 (177-182) beats/min. At higher pacing frequencies,
      both right and left atrial maximal diameter progressively increased, and at 220
      (216-221) beats/min the maximal diameter regained the values obtained at 124
      beats/min. The minimal atrial diameter, which was read at the end of the a wave,
      remained unchanged at heart rates below 180 beats/min but rose significantly at
      higher rates. Our findings indicate progressively reduced atrial filling with
      increasing heart rate and hampered atrial emptying and atrial distension at the
      highest heart rates.

PMID- 2000991
TI  - Adenosine deaminase and adenosine attenuate ventricular arrhythmias caused by
      norepinephrine.
AB  - Twenty-five beagles weighing 9.1 +/- 0.4 kg were used to investigate the
      arrhythmogenic effects of divided doses of intracoronary norepinephrine (50-200
      ng.kg-1.min-1) in the absence and the presence of adenosine deaminase (5 U.kg
      1.min-1). A dose of norepinephrine (100 ng.kg-1.min-1) that caused 66 +/- 17%
      ectopy in the absence of adenosine deaminase caused only 16 +/- 14% ectopy (P
      less than 0.05) in the presence of the enzyme. Ventricular tachycardia caused by
      200 ng.kg-1.min-1 norepinephrine was reduced from 1.2 +/- 0.3 to 0.1 +/- 0.1
      bouts/10 cardiac cycles (P less than 0.05) by adenosine deaminase. In five
      additional dogs, intracoronary adenosine (0.11 mumol/min) terminated sustained
      norepinephrine-induced (200 ng.kg-1.min-1) ventricular tachycardia within 23 +/-
      9 s (P less than 0.05). As long as the adenosine infusion was maintained, a
      normal sinus rhythm was observed. We conclude that both adenosine and adenosine
      deaminase significantly attenuate norepinephrine-induced ventricular arrhythmias.
      A common element beyond the deamination of adenosine, quite possibly ammonia,
      appears to account for these results.

PMID- 2000992
TI  - Calcium is released from the junctional sarcoplasmic reticulum during cardiac
      muscle contraction.
AB  - We have used electron-probe microanalysis (EPMA) to address the question of Ca2+
      release by junctional sarcoplasmic reticulum (JSR) as well as Ca2+ regulation by
      mitochondria (MT) during cardiac muscle contraction. Hamster papillary muscles
      were rapidly frozen during relaxation or at the peak rate of tension rise
      (+dT/dt). Total Ca2+ content was measured by EPMA in the JSR, within a MT, over
      the A band, and in the whole cell, in nine cells per animal (five animals per
      group). JSR Ca2+ content was found to be significantly lower in muscles frozen at
      the peak of contraction [7.3 +/- 1.3 (mean +/- SE) mmol Ca2+/kg dry wt] than in
      those frozen during relaxation (12.5 +/- 1.9 mmol Ca2+/kg dry wt; P less than
      0.01), suggesting that Ca2+ is released from this storage site during cardiac
      muscle contraction. In contrast, MT Ca2+ content did not change significantly
      during contraction (0.4 +/- 0.1 mmol/kg dry wt) compared with relaxation (0.1 +/-
      0.2 mmol/kg dry wt). A third group of muscles was frozen during relaxation after
      pretreatment with 10(-7) M ryanodine. Ca2+ content of the JSR was significantly
      decreased (P less than 0.01) in this group of muscles, (6.4 +/- 1.8 mmol/kg dry
      wt) compared with those frozen during relaxation in the absence of the drug. This
      suggests that the intracellular storage site with a decreased Ca2+ content in
      muscles frozen at the peak of contraction is the ryanodine-releasable store.
      These results provide the first direct measurement of the Ca2+ content of both
      JSR and MT during a normal cardiac muscle contraction and demonstrate that Ca2+
      is released from the JSR during muscle contraction.

PMID- 2000993
TI  - Autoregressive analysis of aortic input impedance: comparison with Fourier
      transform.
AB  - We evaluated the advantages of the autoregressive (AR) model over the
      conventional Fourier transform in estimating aortic input impedance. In 10
      anesthetized open-chest dogs, we digitized aortic pressure and flow at 200 Hz for
      51.20 s under random ventricular pacing and subdivided them into five segments.
      We obtained aortic input impedance over the frequency range of 0.1-20 Hz both by
      AR model and by Fourier transform for various lengths of data, i.e., from one to
      four consecutive segments. For any given data length, the impedance spectrum
      estimated by the AR model was smoother than that obtained by the Fourier
      transform. To evaluate the accuracy of the estimated impedance, we predicted
      instantaneous aortic pressure of the fifth segment by convolving corresponding
      aortic flow with the impulse response of aortic input impedance. The prediction
      error was less with the AR model than that resulting from Fourier transform as
      long as the number of the segments was less than four. We conclude that the AR
      model provides a more accurate estimate of aortic input impedance than does the
      Fourier transform when data length is limited.

PMID- 2000994
TI  - Immune mechanisms in experimental and essential hypertension.

PMID- 2000995
TI  - New adipocyte formation in mice during refeeding after long-term deprivation.
AB  - Cell kinetic characteristics of the epididymal adipose tissue of mice were
      examined during refeeding after prolonged food deprivation. Mature mice were
      given a glucose-electrolyte solution for 20-40 days, and subsequent to a body
      weight loss of 35%, they were given normal mouse food ad libitum. After
      refeeding, their body weight and adipose tissue weight returned to the levels
      before the deprivation. We examined the formation of new adipocytes in the
      epididymal adipose tissue with [3H]thymidine autoradiography. Flash labeling
      experiments revealed that cell proliferation was most active on the 6th day after
      refeeding and decreased thereafter until the 13th day when few labeled cells were
      seen. Cumulative labeling experiments showed that replicated poorly
      differentiated mesenchymal cells developed into adipocytes by storing fat
      droplets. New adipocyte formation was observed in adult mice during refeeding
      after long-term deprivation.

PMID- 2000996
TI  - Plasma glucagon, glucose, and free fatty acid concentrations and secretion during
      prolonged hypothermia in rats.
AB  - Impairment of metabolic substrate mobilization and utilization may be a factor
      limiting survival in hypothermia. Using a newly developed technique for
      maintaining stable low body temperature (Tb), substrate profiles and their
      regulation by glucagon were examined in hypothermic rats (Tb 19 +/- 0.3 degrees
      C) over 20 h. During cooling, plasma glucagon, glucose, and free fatty acid (FFA)
      concentrations increased significantly (536 +/- 55 pg/ml, 304 +/- 26 mg/100 ml,
      and 844 +/- 81 mueq/l, respectively). Plasma glucagon and glucose concentrations
      continued to increase up to 8 h (peaks 810 +/- 103 pg/ml and 451 +/- 33 mg/100
      ml, respectively) and remained high throughout the rest of the hypothermic
      period. FFA concentrations decreased steadily during the hypothermic period.
      Exogenous glucagon (20 micrograms/kg) induced significant increases in plasma
      glucose (+129 +/- 31 mg/100 ml) and FFA concentrations (+351 mueq/l) at 2 h but
      had no effect at 15 h of hypothermia. In vitro evaluation of pancreatic alpha
      cell function indicated that glucagon secretion is independent of temperature
      between 37 and 19 degrees C. Our data indicate that hypothermia is characterized
      by a disturbed substrate metabolism, which is likely due to an imbalance in
      pancreatic alpha- and beta-cell function and a time-dependent decrease in tissue
      sensitivity to glucagon. These deleterious changes may limit survival in
      hypothermia.

PMID- 2000997
TI  - Lateral distribution of hypothalamic signals controlling thermoregulatory
      vasomotor activity and shivering in rats.
AB  - The present study explored the laterality of central nervous thermoregulatory
      control in anesthetized rats by measuring paw skin vasomotor activity and cold
      induced shivering in hind leg muscles during unilateral preoptic area and
      anterior hypothalamus (POAH) warming and electrical stimulation or during
      unilateral thermal stimulation of abdominal skin. Unilateral POAH warming
      produced vasodilation on both sides of the body, but vasodilation on the
      ipsilateral side always either occurred at a lower threshold hypothalamic
      temperature or was stronger than on the contralateral side. In a cold environment
      (5 degrees C), shivering was suppressed simultaneously in both hind legs when one
      side of the POAH was warmed, and shivering reappeared simultaneously on both
      sides when POAH warming stopped. These results suggest that different
      thermoregulatory effectors are regulated in a different way by each side of the
      POAH. Unilateral thermal stimulation of the abdominal skin, on the other hand,
      affected vasomotor activity and shivering equally on both sides of the body, as
      previously reported for its influence on salivary secretion. Skin thermal signals
      from both sides of the body therefore seem to converge before they act on
      different thermoregulatory effector systems.

PMID- 2000998
TI  - Augmentation of endotoxic lethality and glucose dyshomeostasis by phorbol ester.
AB  - To investigate the role of protein kinase C (PKC) activation in the pathogenesis
      of endotoxin (ETX) shock, the in vivo effects of phorbol 12-myristate 13-acetate
      (PMA) on ETX-induced lethality and glucose dyshomeostasis were determined. Fed
      rats (300-400 g) were treated intravenously with incremental doses of Salmonella
      enteritidis ETX and either the vehicle, 110 mg/kg ip dimethyl sulfoxide (DMSO),
      or 0.5 mg/kg ip PMA dissolved in DMSO. PMA significantly increased ETX-induced
      lethality to doses of 1.0-20 mg/kg. PMA augmented the initial hyperglycemia, late
      hypoglycemia, and hyperlactacidemia after 1 mg/kg iv ETX to rats anesthetized
      with pentobarbital sodium. In contrast, 4 alpha-phorbol, a phorbol derivative
      that does not activate PKC, had no effect on either lethality or the glucose and
      lactate responses. Hyperinsulinemia after 1 mg/kg iv ETX was prolonged by PMA but
      not by 4 alpha-phorbol. Insulin tolerance testing (0.5 U/kg iv) produced an
      exaggerated hypoglycemic response in PMA-treated endotoxic (0.33 mg/kg) rats.
      Glucose tolerance to 1.2 g/kg iv was increased by ETX and PMA attenuated the
      increased tolerance. Thus PKC activation may be involved in the pathogenesis of
      lethal endotoxicosis and associated glucose dyshomeostasis.

PMID- 2000999
TI  - Vagotomy attenuates suppression of sham feeding induced by intestinal nutrients.
AB  - The ability of intraintestinal nutrient infusions to suppress sham feeding was
      examined in intact rats and in rats with total subdiaphragmatic vagal
      transections. Vagotomy abolished the suppression of sham feeding by
      intraintestinal infusion of maltose or oleate. Suppression of sham feeding by
      intraintestinal L-phenylalanine was reduced but not abolished by vagotomy. The
      results of this examination indicate that the vagus nerve mediates suppression of
      the sham feeding by intraintestinal maltose and oleate but is only partially
      responsible for suppression of food intake produced by L-phenylalanine. Taken
      together with previously published data these results suggest that effects on
      feeding by specific nutrients may be mediated by anatomically distinct
      populations of visceral afferent neurons.

PMID- 2001000
TI  - Morphine-induced activation of fetal EEG is mediated via central muscarinic
      pathways.
AB  - The effect of morphine on fetal electroencephalogram (EEG) was investigated using
      power spectral analysis. Morphine (0.15-5.0 mg/h) administered directly to the
      fetal lamb altered fetal EEG in three ways. First, morphine altered the relative
      incidence of the three preponderant EEG states [high-voltage slow activity
      (HVSA), transitional, and low-voltage fast activity (LVFA)]. Morphine resulted in
      a dose-dependent reduction in HVSA, with a reciprocal increase in transitional
      state at the lower doses and an increase in LVFA at higher doses. Second,
      morphine resulted in a more fragmented and unstable EEG pattern, with a
      significant increase in the number of state-to-state transitions. Third, there
      was a significant increase in the 90% spectral edge frequency as well as relative
      power distribution in the theta band. Taken together, these data suggest that
      morphine results in activation of the fetal EEG. This effect was completely
      abolished by concurrent intracerebroventricular administration of either methyl
      naloxone or methyl atropine, indicating that it is mediated by specific opioid
      receptors in the central nervous system and involves activation of central
      muscarinic pathways.

PMID- 2001001
TI  - Exercise decreases fat selection in female rats during weight cycling.
AB  - Weight cycling (weight loss and regain) increases fat intake in rats allowed to
      self-select a diet from protein, carbohydrate, and fat sources. This study
      reports the effects of exercise on macronutrient self-selection. Female Sprague
      Dawley rats (5 mo old) self-selected their diet. After 3 wk, rats were assigned
      to one of the following three groups: ad libitum fed sedentary (Con), sedentary
      food restricted to 40% Con intake (R-Sed), or treadmill exercised (20 m/min, 1
      h/day, 6 day/wk) food restricted to 40% Con intake (R-Ex). Food restriction was
      for 3 wk followed by 5 wk of refeeding. This was repeated for a second cycle.
      During restriction, body weight decreased by 30% in R-Sed and by 33% in R-Ex than
      in R-Sed, fat regain was greater in R-Sed. By week 3 of refeeding, total caloric
      consumption did not differ. However, fat selection increased in R-Sed (56% kcal)
      vs. R-Ex (30%) and Con (35%). Fat selection in R-Sed increased further during
      cycle 2 (73% kcal). Resting oxygen consumption decreased during food restriction
      in R-Sed and R-Ex. After refeeding, resting metabolic rate in R-Ex was
      significantly greater than in R-Sed. In conclusion, weight cycling increases
      dietary fat selection and adiposity. Exercise mitigates this effect.

PMID- 2001002
TI  - Reproducibility of osmotic and nonosmotic tests of vasopressin secretion in men.
AB  - We have studied the reproducibility of the thirst and arginine vasopressin (AVP)
      responses to osmotic and hypoglycemic stimulation in healthy volunteers
      undergoing repeat hypertonic (855 mmol/l) saline infusion and insulin tolerance
      tests (ITTs). Hypertonic saline infusion caused similar mean rises in plasma
      osmolality, AVP, and thirst on each occasion. Linear-regression analysis defined
      close relationships between the slopes (r = +0.72, P less than 0.05) and the
      abscissal intercepts (r = +0.89, P less than 0.001) of the regression lines
      relating plasma osmolality (Posmol) and plasma AVP (PAVP), and the group
      intraindividual component of the variance for the slopes and intercepts was 7 and
      0.6%, respectively. There were close correlations between the slopes (r = +0.79,
      P less than 0.02) and the intercepts (r = +0.84, P less than 0.01) of the
      regression lines relating Posmol and thirst, and group intraindividual component
      of the variance was 14 and 0.7%, respectively. Hypertonic saline infusion was
      infused on four occasions in four subjects, and the results showed that the
      linear regression lines relating PAVP and Posmol and thirst and Posmol were
      reproducible within an individual. There were similar falls in blood glucose and
      elevations in PAVP in both ITTs. No relationship was defined between the fall in
      blood glucose and either the rise in PAVP or the area under the AVP curve (AUC).
      The intraindividual component of the variance for the rise in AVP and the AUC was
      77 and 22.5%, respectively. The AVP and thirst responses to osmotic stimulation
      are highly reproducible, but there is considerable intraindividual variation in
      the AVP response to hypoglycemia.

PMID- 2001003
TI  - Conduction blockade in myelinated fibers by gaseous and volatile substances.
AB  - The minimum ambient partial pressure required to reversibly disrupt conducted
      responses in myelinated nerve fibers (Pblock) was determined for 11 gases and
      chloroform. For all but one substance, Pblock was inversely proportional to their
      nonaqueous solubility; large-diameter fibers were less vulnerable than fibers of
      small diameter. No "anesthetic" effect was displayed by SF6. At the Pblock for
      three of the agents, the time for completion of their anesthetic action (tb) was
      proportional to their lipid-to-aqueous solubility ratio. When the ratio was
      large, tb was longer than when the ratio was small; blockade became complete
      after the partial pressure of the agent in the lipid or nonaqueous phase of the
      axon membrane became equal to Pblock. The access of these substances to an
      nonaqueous site was neither pH nor frequency dependent, but in the case of SF6
      access did appear to be limited by its molal volume.

PMID- 2001004
TI  - Food deprivation-induced vs. drug-induced feeding: a behavioral evaluation.
AB  - Several neuroactive substances including neuropeptide Y (NPY), muscimol, and
      norepinephrine (NE) stimulate feeding in satiated rats. In the present study, we
      observed the behavioral patterns of rats stimulated to eat by food deprivation or
      by intracerebroventricular (icv) injection of orexigenic agents to explore the
      hypothesis that such agents produce a behavioral state resembling hunger. Animals
      that were food deprived for 24 h spent the majority of their time eating (35%),
      drinking (5%), resting (44%), and moving (13%) when food was available. If food
      was removed and substituted with a chewable substrate (plastic tube), they chewed
      on tubes for a brief period (5%) but spent most of their time moving (14%) or
      resting (77%). In the absence of food or tubes, they briefly moved about the cage
      (4%) and spent almost all of their time resting (94%). The patterns observed with
      the orexigenic drugs were different, particularly in the absence of food. NPY
      injected rats were more active than deprived rats, spending 22% of their time
      moving in the presence of food, 47% in the presence of tubes, and 37% in the
      absence of food or tubes. Rats injected with muscimol demonstrated a marked
      increase in the time spent chewing and eating. These rats spent 67% of their time
      eating in the presence of food and chewed 25% of the time in the absence of
      either food or tubes. NE-injected rats also chewed when tubes were present (17%)
      or when no food or tubes were present (10%). Lag sequential analysis further
      documented differences in behavioral patterns amongst the various
      treatments.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2001005
TI  - Intestinal glycyl-L-phenylalanine and L-phenylalanine transport in a euryhaline
      teleost.
AB  - The transport mechanisms for the dipeptide glycyl-L-phenylalanine (Gly-Phe) and L
      phenylalanine (Phe) were characterized in fish intestinal brush-border membrane
      vesicles (BBMV). Gly-Phe was rapidly hydrolyzed only intravesicularly with almost
      total hydrolysis occurring even at 10 s. Dipeptide uptake was not stimulated by
      an inward gradient of Na, K, or H. Phe uptake was stimulated by an inward
      gradient of either Na or K but displayed an overshoot phenomenon only in the
      presence of an Na gradient. Kinetic analysis of the effect of substrate
      concentration on transport rate revealed that transport of both Gly-Phe and Phe
      occurred by a saturable process conforming to Michaelis-Menten kinetics. The Km
      for Gly-Phe was 9.8 +/- 3.5 mM, whereas that for Phe in the presence of Na or K,
      respectively, was 0.74 +/- 0.13 and 1.1 +/- 0.37 mM. Maximum uptake for Gly-Phe
      and for Phe in the presence of Na and K was 5.1, 0.9, and 0.4 nmol.mg and protein
      1.5 s-1, respectively. Gly-Phe and Phe transport displayed different patterns of
      inhibition by dipeptides and amino acids. These results suggest that Gly-Phe and
      Phe are transported via different mechanisms, with Gly-Phe being hydrolyzed
      during a carrier-mediated, cation-independent process and Phe being transferred
      via a Na+ cotransport process similar to that described in mammals. During
      conditions of high luminal dipeptide concentrations, the Gly-Phe pathway may make
      a significant contribution to total Phe uptake.

PMID- 2001006
TI  - Enhanced vagal baroreflex response during 24 h after acute exercise.
AB  - We evaluated carotid-cardiac baroreflex responses in eight normotensive men (25
      41 yr) on two different test days, each separated by at least 1 wk. On one day,
      baroreflex response was tested before and at 3, 6, 12, 18, and 24 h after graded
      supine cycle exercise to volitional exhaustion. On another day, this 24-h
      protocol was repeated with no exercise (control). Beat-to-beat R-R intervals were
      measured during external application of graded pressures to the carotid sinuses
      from 40 to -65 mmHg; changes of R-R intervals were plotted against carotid
      pressure (systolic pressure minus neck chamber pressure). The maximum slope of
      the response relationship increased (P less than 0.05) from preexercise to 12 h
      (3.7 +/- 0.4 to 7.1 +/- 0.7 ms/mmHg) and remained significantly elevated through
      24 h. The range of the R-R response was also increased from 217 +/- 24 to 274 +/-
      32 ms (P less than 0.05). No significant differences were observed during the
      control 24-h period. An acute bout of graded exercise designed to elicit
      exhaustion increases the sensitivity and range of the carotid-cardiac baroreflex
      response for 24 h and enhances its capacity to buffer against hypotension by
      increasing heart rate. These results may represent an underlying mechanism that
      contributes to blood pressure stability after intense exercise.

PMID- 2001007
TI  - Impairment of carotid-cardiac vagal baroreflex in wheelchair-dependent
      quadriplegics.
AB  - The incidence of orthostatic hypotension can increase after prolonged exposure to
      chair rest and bedrest and is associated with post-bed rest impairment of the
      carotid-cardiac baroreflex response. We therefore hypothesized that the
      hypotension observed in humans confined to wheelchairs may be manifested by a
      reduced baroreflex sensitivity. We compared baroreflex responses of 16 wheelchair
      dependent (WCD) quadriplegics with those of 15 able-bodied subjects (ABS) matched
      for age, height, and weight. Beat-to-beat R-R intervals were measured during
      application of graded pressures from 40 to -65 mmHg using a neck chamber for
      noninvasive stimulation of the carotid baroreceptors. Changes of R-R intervals
      were plotted against carotid distending pressures. The maximum slope of the
      stimulus-response relationship was greater (P less than 0.0001) in ABS (6.1 +/-
      0.6 ms/mmHg) than in WCD (2.6 +/- 0.4 ms/mmHg). The range of the R-R interval
      response, i.e., the capacity to buffer blood pressure changes, was only 138 +/-
      19 ms in WCD compared with 253 +/- 19 ms in ABS (P less than 0.001). Mean sitting
      systolic-to-diastolic blood pressures in WCD (92/60 mmHg) were less (P less than
      0.0001) than in ABS (120/77 mmHg), although there were no significant differences
      between groups in supine resting blood pressures. Chronic loss of stimulation to
      carotid baroreceptors by routine standing posture is associated with attenuated
      sensitivity and reduced buffer capacity of the arterial baroreflex and
      hypotension during sitting in WCD patients.

PMID- 2001008
TI  - Dynamics of interstitial and intracellular pH in evolving brain infarct.
AB  - We examined the relationships between intracellular pH (pHi) and interstitial pH
      (pHe) in a rat model of focal ischemia. Interstitial pH was measured with pH
      sensitive microelectrodes, and the average tissue pH was measured with the
      [14C]dimethadione method in rats subjected to occlusion of the right middle
      cerebral and common carotid arteries (MCA-CCAO). In normal cortex, pHe and pHi
      were 7.24 +/- 0.97 and 7.01 +/- 0.13 (means +/- SD, n = 6), respectively. In the
      ischemic cortex, pHe fell to 6.43 +/- 0.13, whereas pHi decreased only to 6.86 +/
      0.11 (n = 5) 1 h after MCA-CCAO. After 4 h of ischemia, the pHe was 6.61 +/-
      0.09 and pHi was 6.62 +/- 0.20 (n = 4). Treatment with glucose before ischemia
      markedly lowered the pHe (5.88 +/- 0.17) but not pHi (6.83 +/- 0.03, n = 4)
      measured 1 h after ischemia. In the ischemic cortex of animals made hypoglycemic
      by pretreatment with insulin, neither pHe (7.25 +/- 0.06) nor pHi (6.99 +/- 0.13,
      n = 4) decreased. The demonstrated difference in pHi and pHe indicates that some
      cells remained sufficiently functional to maintain a plasma membrane gradient of
      protons within the evolving infarct. If the calculated pHi values accurately
      reflect the true pHi of cells within zones of severe focal ischemia, then
      cerebral infarction can proceed at pHi levels not greatly altered from normal.

PMID- 2001009
TI  - Nicotinic- and muscarinic-evoked release of canine adrenal catecholamines and
      peptides.
AB  - The tissue content and overflow of norepinephrine (NE), epinephrine (Epi),
      dopamine (DA), Met-enkephalin (Met-Enk), and neuropeptide Y (NPY) from isolated,
      retrogradely perfused dog adrenal glands were studied. Under resting conditions,
      approximately 25% of the overflow of autocoids from the glands was Ca2+
      dependent; the cholinergic antagonists hexamethonium and atropine had no effects
      on basal efflux. Stimulation with the nicotinic agonist 1,1-dimethyl-4
      phenylpiperazinium iodide (DMPP; 3 or 50 microM) or with the muscarinic agonist
      pilocarpine (50 microM or 1 mM) evoked releases of autocoids. These releases were
      blocked or dramatically reduced by appropriate antagonists or by the removal of
      Ca2+ from the perfusate. Expressed as percentages of tissue stores, the rank
      order of overflow of autocoids was E approximately DA much greater than NE during
      resting conditions, DA much greater than E approximately NE during stimulation
      with 50 microM DMPP, and DA greater than Epi greater than NE during stimulation
      with 1 mM pilocarpine. These data are consistent with different mechanisms of
      release for the catecholamines, perhaps from different cell populations. The data
      support corelease of peptides and catecholamines, although clear pairing of
      autocoids could not be confirmed.

PMID- 2001010
TI  - Fatigue and recovery of rat soleus muscle are influenced by inhibition of an
      intracellular carbonic anhydrase isoform.
AB  - Carbonic anhydrase III (CA III; EC 4.2.1.1) is the most abundant cytosolic enzyme
      in type I skeletal muscle fibers. Methazolamide, a specific CA inhibitor, was
      used to characterize the effects of inhibiting CA III on the resistance to
      fatigue and recovery of the rat soleus muscle using a 60-min fatigue protocol
      performed in vitro at 25 degrees C. Incubation with 10(-3) M methazolamide
      resulted in a smaller decrease in tension production during the fatigue protocol,
      thereby increasing the total tension-time integral for the fatigue test. However,
      the rate and extent of recovery after the test were lower in the experimental
      group compared with the control group. A similar effect was observed at
      physiological temperature (35 degrees C). The results indicate that inhibition of
      CA III significantly influences tension production as early as 30 s into the
      stimulation protocol. Inhibition of CA III only during the recovery period did
      not influence the recovery profile, thereby indicating that the impaired recovery
      was related to the presence of methazolamide during the stimulation period.

PMID- 2001011
TI  - Hypo- and hypercalcemic peptides in fish pituitary glands.
AB  - Immunoreactive parathyroid hormone (irPTH), PTH-related peptide (PTHrp), and
      stanniocalcin-like peptides were detected in Coho salmon pituitary glands. The
      PTH, PTHrp, and stanniocalcin immunoreactivity of the salmon pituitary was
      separated by high-performance liquid chromatography purification into distinct
      peptide fractions that coeluted with pure preparations of these hormones.
      Stanniocalcin was localized by immunocytochemistry in the neurohypophysis and
      preoptic area of the platyfish brain, in areas in which irPTH has previously been
      detected in other teleosts. Although it is well established that the fish
      pituitary exerts hypercalcemic control over calcium metabolism, these results
      demonstrate the presence of hyper- and hypocalcemic peptides in teleost pituitary
      glands. The detection of PTHrp in the fish pituitary is the first report of its
      presence outside of mammalian species and suggests an early evolutionary
      divergence of PTH and PTHrp from an ancestral gene.

PMID- 2001012
TI  - Water hydrogen incorporation into body fat in pigs: effect on double/triple
      labeled water method.
AB  - A basic assumption of the doubly labeled water (DLW) and triply labeled water
      (TLW) methods for measuring water flux (rH2O), CO2 production (rCO2), and
      fractionated water loss (X) is that the H of body water only leaves the body as
      water. Any loss of isotopes in other products will introduce an error into these
      techniques. The body fat represents the largest potential sink for water H. 2H
      sequestration into the carcass fatty acids was investigated in eight pigs labeled
      with 2H2O for 21 days. rCO2 was measured simultaneously in respiration chambers
      to allow an accurate assessment of the effect of 2H sequestration on the
      estimated rCO2. The fat content of the diet (1.63%), level of intake, and stage
      of maturity were all designed to give the widest possible range of sequestration
      effects. Four animals were restricted to their estimated maintenance requirement
      and four were allowed to feed ad libitum giving a range of weight gain from 100
      to 650 g/day. This was reflected in the estimated error on rH2O (+0.42% in the
      restricted group and +2.52% in the fast-growing animals) and on rCO2 (-1.30 and 
      7.59%, respectively). The error on the calculation of X using TLW was +0.03 units
      in the restricted group and +0.20 units in the fast-growing animals. The error of
      +0.2 on X propagates through to an underestimate of rCO2 of approximately 4%, and
      since this is additive with the error on DLW the ultimate error on rCO2 using TLW
      would be approximately -12%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2001013
TI  - Differential baroreflex modulation of human vagal and sympathetic activity.
AB  - We compared baroreflex modulation of human vagal-cardiac and sympathetic muscle
      activity in healthy volunteers by measuring R-R interval and peroneal nerve
      responses to a profile of positive and negative (40-65 mmHg) R-wave-triggered
      neck pressure steps during held expiration. R-R interval responses were sigmoid.
      Sympathetic activity increased abruptly with 40 mmHg pressure but returned to
      baseline levels as this pressure was maintained. The first decremental pressure
      step reduced sympathetic activity to below baseline, and the next three steps
      inhibited activity. During the final three steps, sympathetic activity increased
      to baseline, and after the return of neck pressure to ambient levels sympathetic
      activity increased to the highest levels recorded. Our results suggest that on a
      second-by-second basis human vagal-cardiac responses are determined simply by the
      net level of baroreceptor stimulation. Sympathetic muscle responses are
      determined complexly by the direction of changes (rising or falling) more than
      absolute arterial pressure levels and importantly by inputs from both carotid and
      aortic baroreceptors.

PMID- 2001014
TI  - Variable series elasticity accounts for Fenn effects of skeletal and cardiac
      muscles: a comment.

PMID- 2001015
TI  - Barbiturate protection and cardiac surgery: a different result.

PMID- 2001016
TI  - Effect of thiopental on neurologic outcome following coronary artery bypass
      grafting.
AB  - To determine if thiopental reduces the incidence of neurologic sequelae after
      coronary artery surgery, we prospectively studied 300 patients undergoing
      coronary artery bypass grafting. Patients who had no history of neurologic or
      psychiatric illness were randomly assigned to receive either a thiopental
      infusion or a saline placebo infusion beginning with the administration of
      heparin and ending just after aortic decannulation. The patients received an
      opioid-relaxant anesthetic administered by an anesthesiologist who was not
      involved in this investigation and who was blinded to the test infusion. One of
      the investigators infused either saline or thiopental to produce an isoelectric
      electroencephalogram with 30-45 s between bursts. Standardized neurologic
      examinations were performed preoperatively and on the 2nd and 5th postoperative
      days by one of the blinded investigators. The group of patients receiving
      thiopental required a longer time for awakening (6.4 +/- 3.9 vs. 4.0 +/- 2.4 h,
      mean +/- SD, P less than 0.05) and for tracheal extubation (22.4 +/- 18.4 vs.
      17.4 +/- 9.6 h, P less than 0.05), and a greater number of these patients were
      lethargic on the 2nd postoperative day. More patients receiving thiopental
      required vasoconstrictors during the thiopental loading and cardiopulmonary
      bypass (CPB) periods, while a greater number of patients receiving placebo
      required vasodilators. A greater number of patients receiving thiopental required
      inotropic drugs during separation from CPB. Despite the above differences, only 2
      of the 151 patients in the placebo group (1.3%) and 5 of the 149 patients in the
      thiopental group (3.3%) experienced strokes (P = 0.2535).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 2001017
TI  - The neuromuscular effects of desflurane, alone and combined with pancuronium or
      succinylcholine in humans.
AB  - The neuromuscular effects of desflurane administered alone were studied in ten
      healthy human volunteers aged 20-27 yr. Also, the dose-response relationships of
      pancuronium and succinylcholine in surgical patients during anesthesia with
      desflurane (n = 13) were compared to those during isoflurane anesthesia (n = 14).
      In the volunteers, we measured the mechanical response of the adductor pollicis
      muscle to stimulation of the ulnar nerve in a train-of-four (TOF) sequence at 2
      Hz and at tetanic frequencies of 50, 100, and 200 Hz, each administered for 5 s.
      Amplitudes of the first response (T1) in each TOF sequence and the ratios of the
      fourth TOF response (T4) to the first were similar at 3, 6, and 9% desflurane and
      decreased significantly only at 12% (P less than 0.05). Desflurane concentrations
      of 3-12% caused tetanic fade (greater than 10% decrement in amplitude) at 50,
      100, and 200 Hz. The addition of N2O and the duration of anesthetic exposure did
      not alter desflurane's neuromuscular effects. The only neuromuscular variable
      influenced by CO2 was T1 amplitude, which decreased as arterial CO2 tension
      (PaCO2) increased. The doses of pancuronium that depressed T1 amplitude by 50%
      (ED50) were similar during anesthesia with 1.25 MAC desflurane, 10.5 +/- 2.8
      micrograms/kg (mean +/- SD) and 1.25 MAC isoflurane, 12.3 +/- 5.0 micrograms/kg.
      The ED50 doses of succinylcholine were similar during anesthesia with desflurane
      132 +/- 76 micrograms/kg and isoflurane 123 +/- 36 micrograms/kg. We conclude
      that desflurane significantly depresses neuromuscular function and augments the
      action of pancuronium and succinylcholine to a degree similar to that of
      isoflurane.

PMID- 2001018
TI  - Recovery profile after desflurane-nitrous oxide versus isoflurane-nitrous oxide
      in outpatients.
AB  - Thirty-eight healthy outpatients undergoing elective surgical procedures lasting
      1-3 h were randomly assigned to receive either desflurane 3% (approximately 0.5
      MAC) or isoflurane 0.6% (approximately 0.5 MAC) for maintenance of general
      anesthesia with nitrous oxide 60% in oxygen after a standardized induction
      sequence consisting of fentanyl 3 micrograms.kg-1, thiopental 4 mg.kg-1, and
      succinylcholine 1-1.5 mg.kg-1, intravenously. Although anesthetic conditions were
      similar during operations in the two treatment groups, significant differences
      were noted in the recovery profiles as measured by elimination kinetics,
      psychometric testing, and visual analog scales (to assess subjective feelings).
      The time required for the end-tidal concentration to decrease by 50% was 2.5 +/-
      0.8 min for desflurane vs. 9.5 +/- 3.4 min for isoflurane (mean +/- standard
      deviation [SD]). Times to awakening and ability to follow simple commands were
      significantly shorter after desflurane than after isoflurane (5.1 +/- 2.4 vs.
      10.2 +/- 7.7 min 6.5 +/- 2.3 min vs. 11.1 +/- 7.9 min, respectively).
      Postoperatively, patients who received desflurane exhibited less impairment of
      cognitive function (as measured using the Digit-Symbol Substitution Test) than
      did those who received isoflurane. Furthermore, visual analog scores indicated
      that patients receiving desflurane experienced significantly less discomfort
      (pain), drowsiness, fatigue, clumsiness, and confusion in the early postoperative
      period. We conclude that desflurane may offer clinical advantages over isoflurane
      when used for maintenance of anesthesia during outpatient surgical procedures.

PMID- 2001019
TI  - Desflurane and isoflurane in surgical patients: comparison of emergence time.
AB  - In order to examine the clinical potential of desflurane (difluoromethyl-1-fluoro
      2,2,2-trifluoroethyl ether) in humans, a randomized, controlled study was
      designed to compare time of emergence from anesthesia in patients undergoing
      elective surgery under desflurane anesthesia to that of patients under isoflurane
      anesthesia. Twenty-eight patients were randomly divided into four groups. Group 1
      received isoflurane 0.65 MAC; group 2, desflurane 0.65 MAC; group 3, isoflurane
      1.25 MAC; and group 4, desflurane 1.25 MAC. Anesthesia was induced with sodium
      thiopental, and N2O 60% was added to the volatile agent. Mean anesthetic exposure
      times (min [mean +/- SD]) were 108 +/- 49 in group 1, 132 +/- 46 in group 2, 147
      +/- 74 in group 3, and 166 +/- 71 in group 4, with no significant differences
      between groups. The times from discontinuation of anesthetic gases until patients
      opened their eyes and squeezed the investigator's hand in response to a command
      were averaged and recorded as "emergence time." Emergence time was significantly
      less with desflurane than with isoflurane given at the same MAC. Patients
      receiving isoflurane 0.65 MAC responded to commands 15.6 +/- 4.3 min after
      discontinuation of the anesthetic; patients in the desflurane 0.65 MAC group
      responded in 8.8 +/- 2.7 min (P less than 0.01). Emergence time for isoflurane
      1.25 MAC was 30.0 +/- 11.0 min; for desflurane 1.25 MAC it was 16.1 +/- 6.0 min
      (P less than 0.05). Our results confirm that emergence from desflurane anesthesia
      is more rapid than from isoflurane.

PMID- 2001020
TI  - Clinical characteristics of desflurane in surgical patients: minimum alveolar
      concentration.
AB  - Desflurane (formerly I-653) is a new inhalaticnal anesthetic with a promising
      pharmacokinetic profile that includes low solubility in blood and tissue,
      including fat. Since its lipid solubility is less than that of other volatile
      agents, it may have lower potency. Low solubility would be expected to increase
      the rate at which alveolar concentration approaches inspired concentration during
      induction as well as to increase the rate of elimination of desflurane from blood
      at emergence. We determined the minimum alveolar concentration (MAC) of
      desflurane in 44 unpremedicated ASA physical status 1 or 2 patients undergoing
      elective surgery. We prospectively studied four patient groups distinguished by
      age and anesthetic regimen: 18-30 versus 31-65 yr and desflurane in 60% N2O/40%
      O2 versus desflurane in O2. Anesthesia was induced with desflurane or desflurane
      in 60% N2O/40% O2. MAC was determined by a modification of Dixon's up-and-down
      method with increments of 0.5% desflurane. The MAC of desflurane in O2 was 7.25
      +/- 0.0 (mean +/- SD) in the 18-30-yr age group, and 6.0 +/- 0.29 in the 31-65-yr
      group; the addition of 60% N2O reduced the MAC to 4.0 +/- 0.29 and 2.83 +/- 0.58,
      respectively. The median time from discontinuation of desflurane to an
      appropriate response to commands was 5.25 min. Desflurane appears to be a mild
      airway irritant but was well tolerated by all patients.

PMID- 2001022
TI  - Clinical utility of a position-monitoring catheter in the pulmonary artery.
AB  - Unsuspected distal migration of the tip of the pulmonary artery catheter may
      cause life-threatening complications. We prospectively evaluated the clinical
      utility of the PA Watch Catheter in 25 patients after cardiac surgery by hourly
      measurements of pulmonary artery (distal lumen), right ventricular (middle
      lumen), and central venous (proximal lumen) pressures. The catheter was
      considered to be in the proper position when the middle lumen port, located 10 cm
      from the tip, transmitted a right ventricular pressure waveform. Satisfactory
      initial catheter placement was obtained in 24 of 25 patients. During the 28.4 +/-
      1.8 h of postoperative monitoring, clinically unsuspected distal catheter
      migration, indicated by the presence of a pulmonary artery pressure waveform in
      the middle lumen port, occurred in 12 of the 25 patients (48%). In these
      patients, 20 episodes occurred and required catheter withdrawal distances of 1.8
      +/- 0.3 cm (range 1-6 cm). The PA Watch Catheter proved to be a useful indicator
      of unsuspected distal catheter migration in the postoperative period. The PA
      Watch Catheter allows assessment of catheter tip placement in the proximal
      pulmonary artery and may decrease catheter-induced complications.

PMID- 2001021
TI  - The electroencephalographic effects of desflurane in humans.
AB  - The electroencephalographic (EEG) effects of a new inhaled anesthetic are of
      interest because of the potential of such agents to produce excitatory
      (convulsant) activity and because of the potential usefulness of the EEG as an
      indicator of anesthetic depth and cerebral activity. Accordingly, we examined the
      EEG in 12 healthy, young male volunteers during desflurane anesthesia. Each
      subject had a baseline recording and then steady-state exposure to 6, 9, and 12%
      (0.83, 1.24, and 1.66 MAC) desflurane in O2 alone, and to 3, 6, and 9% desflurane
      in O2 with 60% N2O. The sequence of doses and the presence of N2O were
      randomized. We used mechanical ventilation to maintain normocapnia at each dose
      level. We also tested the effects of hypercapnia secondary to spontaneous
      ventilation. Additionally, at 1.24 MAC, subjects' lungs were hyperventilated to a
      PCO2 of 25.8 +/- 0.7 mmHg and exposed to rhythmic, loud clapping to attempt to
      provoke excitatory phenomena. Finally, after at least 6 h exposure to desflurane,
      we repeated measurements at 0.83 and 1.66 MAC to assess possible tolerance. Four
      channels of EEG were monitored visually, and at each dose, a quantitative EEG
      analysis was performed. Desflurane produced EEG changes comparable to those
      observed with equipotent levels of isoflurane. No epileptiform activity was seen.
      Desflurane significantly suppressed EEG activity; prominent burst suppression was
      seen at 1.24 MAC and higher. Substitution of N2O for 0.42 MAC desflurane reduced
      the degree of EEG suppression relative to the equipotent administration of
      desflurane and O2. Quantitative EEG measures for the early doses and for the
      later, repeated exposures did not differ.

PMID- 2001023
TI  - Atracurium decay and the formation of laudanosine in humans.
AB  - Several groups of investigators have reported that the plasma concentrations of
      laudanosine, a metabolite of atracurium, are high immediately after
      administration of atracurium and thereafter decline. Such a time profile of a
      metabolite in plasma is very unusual. The authors describe a model of atracurium
      decay and laudanosine disposition that satisfactorily explains these data. The
      model reveals the following: 1) each atracurium molecule is degraded into two of
      laudanosine; 2) the generation of laudanosine occurs through two processes--a
      rapid one, involving approximately 31% of the atracurium dose and proceeding with
      a half-life of 0.25 min, and a slower one, involving the residual 69% and
      proceeding with a half-life of 51 min; 3) atracurium degradation by Hofmann
      elimination proceeds in the central and the noncentral compartments; 4)
      laudanosine formed from atracurium gains access to its central compartment and
      disappears from plasma in a biexponential pattern; 5) in cirrhotic patients, only
      18% of the atracurium dose is degraded rapidly and laudanosine is disposed of
      more slowly. The authors propose that the rapid degradation of atracurium in
      plasma proceeds through a nucleophilic substitution reaction, with plasma
      nucleophiles substituting for the laudanosine moiety in atracurium. Because both
      laudanosine moieties in atracurium are required to establish and sustain plasma
      concentrations of laudanosine, excretion of atracurium or its degradation through
      pathways not generating laudanosine must be small.

PMID- 2001024
TI  - The induction dose of propofol in infants 1-6 months of age and in children 10-16
      years of age.
AB  - The propofol dose needed for satisfactory induction of anesthesia was determined
      in 22 infants 1-6 months of age and 22 children 10-16 yr of age. A single bolus
      of propofol was given over 10 s. Thirty seconds after injection the lid reflex
      was tested and the anesthesia mask was applied. The patient was considered to be
      asleep if there were no gross movements during the next 30 s while the patient
      breathed O2. The dose required for satisfactory induction in 50% of patients
      (ED50) (+/- SE) was 3.0 +/- 0.2 mg/kg in infants and 2.4 +/- 0.1 mg/kg in older
      children (P less than 0.02). Pain on injection occurred in 50% of the infants and
      18% of the children.

PMID- 2001025
TI  - Percutaneous lumbar sympathectomy: a comparison of radiofrequency denervation
      versus phenol neurolysis.
AB  - A new percutaneous approach to sympathectomy using radiofrequency denervation has
      seemed to offer longer duration and less incidence of postsympathetic neuralgia
      as compared to phenol sympathetic blocks. To compare these techniques, 17
      patients underwent either phenol lumbar sympathetic blocks (n = 9) or
      radiofrequency denervation (n = 8). Duration of sympathetic block was followed by
      a sweat test and temperature measurements. Results indicate that 89% of patients
      in the phenol group showed signs of sympathetic blockade after 8 weeks, as
      compared to 12% in the radiofrequency group (P less than 0.05). Although the
      incidence of post sympathetic neuralgia appears to be less with radiofrequency
      denervation, further refinement of needle placement to ensure complete lesioning
      of the sympathetic chain will be required before the technique can offer
      advantages over current phenol techniques.

PMID- 2001026
TI  - Postoperative myocardial ischemia in patients undergoing coronary artery bypass
      graft surgery. S.P.I. Research Group.
AB  - Cardiac morbidity and mortality after coronary artery bypass graft (CABG) surgery
      continue to be significant problems. To determine the prevalence,
      characteristics, and prognostic importance of postoperative myocardial ischemia
      after CABG surgery, the authors monitored 50 patients continuously for 10
      perioperative days with the use of two-lead electrocardiography (ECG). ECG
      changes consistent with ischemia were defined as a reversible ST depression of 1
      mm or greater or an elevation of 2 mm or greater from baseline, lasting at least
      1 min. Baseline was adjusted for positional changes and temporal drift. All
      episodes were verified, with the use of the ECG monitor printout (ECG complexes),
      by two independent blinded investigators. Clinical care was not controlled by
      study protocol, and clinicians were unaware of the research data collected.
      Twenty-six of 50 patients (52%) had 207 episodes of perioperative ischemia (3,409
      ischemic minutes). Postoperatively, ischemia developed in 48% of patients,
      compared with 12% preoperatively and 10% intraoperatively before bypass.
      Postoperative ischemia was most common in the early period (postoperative days
      [PODs] 0-2; 38% of patients), peaking during the first 2 h after
      revascularization, and less common during the late postoperative period (PODs 3
      7; 24% of patients). Almost all (120 of 122; 98%) postoperative episodes (after
      tracheal extubation) were asymptomatic: only 9 of 70 (13%) early episodes were
      detected by clinical ECG monitoring. Postoperative ischemia did not appear to be
      related to acute changes in myocardial oxygen demand: only 39% of the
      postoperative episodes were preceded by a greater than 20% increase in heart
      rate. However, tachycardia persisted throughout the postoperative week (22-33% of
      all heart rates greater than 100 beats per min), and patients with postoperative
      ischemia (POD 0) more frequently had tachycardia (median 43% vs. 12% of the time;
      P less than 0.01). Five adverse cardiac outcomes occurred on the day of surgery;
      all five were preceded by postoperative ischemia, three by intraoperative
      ischemia before bypass, and none by preoperative ischemia. Patients with late
      postoperative ischemia did not have an adverse cardiac outcome. The authors
      conclude the following: 1) ischemia is more prevalent postoperatively than
      preoperatively or intraoperatively before bypass; 2) the incidence of
      postoperative ischemia peaks shortly after revascularization, during which time
      it is symptomatically silent, difficult to detect, and related to adverse cardiac
      outcome; 3) late postoperative ischemia also is silent, but it is less prevalent
      and not associated with in-hospital adverse cardiac outcome; and 4) a
      relationship between ischemia and persistently elevated postoperative heart rate
      may exist and warrants additional investigation.

PMID- 2001027
TI  - Percutaneous loss of desflurane, isoflurane, and halothane in humans.
AB  - We studied the percutaneous losses of the new inhaled anesthetic, desflurane (I
      653), and of isoflurane and halothane during anesthetic administration and
      elimination in seven healthy male volunteers. Anesthesia was induced and
      maintained with midazolam, thiopental, and fentanyl. We administered 70% N2O for
      30 min, and then administered 2% desflurane, 0.4% isoflurane, and 0.2% halothane
      concurrently with 65% N2O for 30 min. Inspired, end-tidal, and mixed-expired gas
      samples were collected during administration of the volatile agents and for 5-7
      days of elimination. The right arm and hand of each subject was enclosed in a
      sealed glass cylinder having a port at each end, one for sampling and both for
      flushing with N2 after anesthetic administration and every 15 min thereafter. We
      sampled gases from the cylinder during administration and for the 150 min of
      elimination and analyzed their anesthetic concentrations by gas chromatography.
      The surface area of the enclosed portion of the arm was measured, and the total
      body surface area was calculated. All values were normalized to (i.e., divided
      by) the end-tidal (alveolar) concentration at the end of administration. During
      administration, percutaneous loss of halothane was 3.5 times that of desflurane
      and 2 times that of isoflurane. During elimination, the loss of halothane was 6
      times and 2 times greater than the loss of desflurane and isoflurane,
      respectively. Percutaneous loss of halothane significantly exceeded that of
      isoflurane. The elimination values included an estimate of elimination after 150
      min. The percutaneous loss of each anesthetic was 2- to 3-fold greater during
      elimination than administration.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2001028
TI  - Kinetics of desflurane, isoflurane, and halothane in humans.
AB  - The low solubility of desflurane in blood and tissues suggests that the partial
      pressures of this agent in blood and tissues should approach the inspired partial
      pressure more rapidly than would the blood and tissue partial pressures of other
      potent inhaled anesthetics. We tested this prediction, comparing the
      pharmacokinetics of desflurane with those of isoflurane, halothane, and nitrous
      oxide in eight volunteers. We measured the rate at which the alveolar (endtidal)
      (FA) concentration of nitrous oxide increased towards an inspired (FI)
      concentration of 65-70%, and then measured the concurrent increase in FA and
      mixed expired concentrations (FM) of desflurane, isoflurane, and halothane at
      respective FI values of 2.0%, 0.4%, 0.2%. Minute ventilation (VE) was measured
      concurrently with the measurements of anesthetic concentrations. The potent
      vapors were administered for 30 min; administration of nitrous oxide continued
      throughout the period of anesthesia. For the potent agents, we also measured VE,
      FA, and FM for 5-7 days of elimination. We used FA/FI and FA/FA0 (FA0 = the last
      FA during the administration of each anesthetic) to define the rate of increase
      of anesthetic in the lungs and the rate of elimination of anesthetic,
      respectively. FA/FI values at 30 min of administration were: (mean +/- SD)
      nitrous oxide 0.99 +/- 0.01, desflurane 0.90 +/- 0.01, isoflurane 0.73 +/- 0.03,
      and halothane 0.58 +/- 0.04. FA/FA0 values after 5 min of elimination were:
      desflurane 0.14 +/- 0.02, isoflurane 0.22 +/- 0.02, and halothane 0.25 +/- 0.02.
      Recovery (volume of anesthetic recovered during elimination per volume taken up)
      of desflurane (105 +/- 25%) equalled recovery of isoflurane (102 +/- 13%) and
      exceeded recovery of halothane (64 +/- 9%). Time constants for a five-compartment
      mammillary model for halothane and isoflurane differed for the lungs, fat group,
      and hepatic metabolism, and exceeded those for desflurane for all compartments.
      In summary, we found that FA/FI of desflurane increases more rapidly and that
      FA/FA0 decreases more rapidly in humans than do these variables with other
      available potent anesthetics. We also found that desflurane resists
      biodegradation in humans and so may have little or no toxic potential.

PMID- 2001029
TI  - Enhancement of somatosensory evoked potentials by etomidate in cats: an
      investigation of its site of action.
AB  - Enhancement of somatosensory evoked potentials by etomidate has been reported in
      recent clinical studies. This investigation was designed to investigate the
      central nervous system site of action responsible for this effect. Six adult cats
      were anesthetized with halothane (0.8-1%) in a mixture of 50% N2O in O2. A
      recording electrode was placed stereotactically in the ventral posterior lateral
      nucleus of thalamus (VPL), and a ball electrode was placed over the surface of
      the hind limb region of primary sensory cortex. Somatosensory evoked potentials
      in response to stimulation of tibial nerve thus were simultaneously recorded from
      cerebral cortex and VPL. The effect of two doses (1 and 3 mg.kg-1) of etomidate
      given 2 h apart on the latency and amplitude of cortical (positive wave at 15 ms)
      and thalamic (positive deflection at 10 ms, followed by negative deflection at 17
      ms) evoked potentials was studied. There was no significant effect of etomidate
      on either latency or amplitude of early, positive thalamic potentials. Both doses
      of etomidate caused a significant increase in the latency and amplitude of
      cortical potentials. The mean latency of cortical potential increased by 1.72 ms
      (11%) after the 1 mg.kg-1 dose and 2.3 ms (15.9%) after the 3 mg.kg-1 dose. The
      maximum mean increase in the amplitude of cortical potentials was 14.3 microV
      (mean increase 78%, range 28-241%) after 1 mg.kg-1 and 19.1 microV (mean increase
      112%, range 28-202%) after 3 mg.kg-1. Cortical amplitude remained significantly
      elevated for 30 min after 1 mg.kg-1 and for the remainder of the study period (60
      min) after 3 mg.kg-1.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2001030
TI  - The cerebral and systemic hemodynamic and metabolic effects of desflurane-induced
      hypotension in dogs.
AB  - The cerebral and systemic hemodynamic and metabolic effects of hypotension
      induced with desflurane were examined in 11 dogs. During a steady-state baseline
      period under 1 MAC desflurane (7.2%), the following were measured or derived:
      arterial, pulmonary artery, and pulmonary artery occlusion pressures; arterial,
      mixed venous, and sagittal sinus blood gases; cardiac index and cerebral blood
      flow (CBF); whole-body and cerebral O2 consumption; systemic and cerebral
      vascular resistance; intracranial pressure; and blood glucose and lactate
      concentrations. After the baseline period, hypotension to a mean arterial
      pressure (MAP) of 50 mmHg was produced by 15.5% (2.2 MAC), and hypotension to an
      MAP of 40 mmHg was produced by 17.1% (2.4 MAC) for 1 h. During this hypotensive
      period all measurements were taken at 5- or 15-min intervals. At the end of the
      hypotensive period, brain biopsy specimens were taken for measurement of cerebral
      concentrations of ATP, phosphocreatine, and lactate to determine whether there
      was any metabolic evidence of cerebral ischemia. Desflurane-induced hypotension
      produced a significant, 40-50% decrease in cardiac index with a significant
      change in systemic vascular resistance at the lower blood pressure, but produced
      little change in heart rate. Even though whole-body O2 consumption did not
      decrease, adequate peripheral perfusion was maintained with the lower cardiac
      output, as evidenced by lack of accumulation of blood lactate. Induced
      hypotension caused a significant, 50 (at MAP = 50 mmHg) to 64% (at MAP = 40 mmHg)
      decrease in cerebral perfusion pressure, accompanied by a significant, 36 (at MAP
      = 50 mmHg) to 60% (at MAP = 40 mmHg) decrease in CBF.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 2001031
TI  - Depression of atrial rate, atrioventricular nodal conduction, and cardiac
      contraction by diltiazem and volatile anesthetics in isolated hearts.
AB  - The direct effects of isoflurane, halothane, and enflurane alone or combined with
      diltiazem were examined in 49 isolated perfused guinea pig hearts. Recording
      electrodes were placed in the right atrium and left ventricular septal wall to
      measure spontaneous atrial rate and atrioventricular conduction time (AVCT). The
      right atrium was paced at 3-7 Hz (n = 10) to examine rate-dependent effects on
      AVCT, Wenckebach's periodicity, and ventricular response rates with
      atrioventricular (AV) block. Isovolumetric left ventricular pressure (LVP) was
      measured with a saline-filled balloon placed through the mitral valve. Hearts
      were perfused with oxygenated Krebs-Ringer's solution at 55 mmHg equilibrated
      with low or high concentrations of isoflurane (0.7 and 1.5%), halothane (0.5 and
      1%), or enflurane (1.1 and 2.2%). Hearts were also perfused with a low or high
      concentration of diltiazem (75 and 150 ng/ml) alone and during anesthetic
      exposure. Significant findings of combined exposure were as follows: 1) the low
      isoflurane, halothane, or enflurane concentration plus a low or high diltiazem
      concentration decreased LVP compared with control and diltiazem alone; low
      isoflurane plus the high diltiazem concentration decreased LVP more than
      isoflurane alone. The high isoflurane, halothane, or enflurane concentration plus
      the low or the high diltiazem concentration decreased LVP from control,
      anesthetics and diltiazem alone. Diltiazem plus halothane or enflurane decreased
      LVP more than diltiazem plus isoflurane. 2) Diltiazem plus low or high
      isoflurane, halothane, or enflurane concentrations decreased spontaneous atrial
      rate from control and the agents alone, except the high isoflurane concentration
      plus the low diltiazem concentration was not greater than that of isoflurane
      alone. Diltiazem plus halothane or enflurane decreased atrial rate more than
      diltiazem plus isoflurane. 3) Low and high diltiazem concentration plus low
      isoflurane, halothane, or enflurane concentrations did not prolong AVCT more than
      the individual agents alone, but low or high diltiazem plus high isoflurane,
      halothane, or enflurane concentrations increased AVCT more than each anesthetic
      alone. In nonpaced hearts, AV block occurred only with high diltiazem plus low
      enflurane (23%) concentrations and the high enflurane concentration (31%). 4) In
      hearts paced at 5 and 6 Hz, AVCT increased above controls during a low or high
      concentrations of diltiazem, during enflurane, and during the low or high
      concentration of diltiazem plus enflurane; AVCT increased more with the low
      concentration of diltiazem plus enflurane than with the low diltiazem
      concentration alone.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 2001032
TI  - Enhanced mobilization of intracellular Ca2+ induced by halothane in hepatocytes
      isolated from swine susceptible to malignant hyperthermia.
AB  - Halothane, in a dose-dependent manner, induced the release of intracellular Ca2+
      in hepatocytes prepared from swine. The magnitude of the release induced by
      halothane was greater for hepatocytes prepared from animals susceptible to
      malignant hyperthermia (MH) than for those from normal swine. Two different
      methods were used to ascertain the release of Ca2+ induced by halothane: 1) the
      release of 45Ca2+ from nonmitochondrial stores of saponin-permeabilized
      hepatocytes was measured; and 2) changes in luminescence from intact hepatocytes
      loaded with the Ca2(+)-sensitive photoprotein aequorin were recorded. It was also
      observed that, although 1,4,5-inositol trisphosphate (IP3), guanosine-5
      triphosphate, and arachidonic acid all induced a significant release of 45Ca2+
      from permeabilized swine hepatocytes, only the quantities of 45Ca2+ released by
      IP3 were significantly greater for the hepatocytes prepared from the animals
      susceptible to MH. These data indicate an abnormal Ca2+ homeostasis in
      hepatocytes isolated from swine susceptible to MH, which supports the hypothesis
      that membrane systems from multiple organs may be affected in this genetic
      disorder.

PMID- 2001033
TI  - Comparison of the systemic and coronary hemodynamic actions of desflurane,
      isoflurane, halothane, and enflurane in the chronically instrumented dog.
AB  - The systemic and coronary hemodynamic effects of desflurane were compared to
      those of isoflurane, halothane, and enflurane in chronically instrumented dogs.
      Since autonomic nervous system function may significantly influence the
      hemodynamic actions of anesthetics in vivo, a series of experiments also was
      performed in the presence of pharmacologic blockade of the autonomic nervous
      system. Eight groups comprising a total of 80 experiments were performed on 10
      dogs instrumented for measurement of aortic and left ventricular pressure, the
      peak rate of increase of left ventricular pressure (dP/dt), subendocardial
      segment length, coronary blood flow velocity, and cardiac output. Systemic and
      coronary hemodynamics were recorded in the conscious state and after 30 min
      equilibration at 1.25 and 1.75 MAC desflurane, isoflurane, halothane, and
      enflurane. Desflurane (+79 +/- 12% change from control) produced greater
      increases in heart rate than did halothane (+44 +/- 12% change from control) or
      enflurane (+44 +/- 9% change from control) at 1.75 MAC. Desflurane preserved mean
      arterial pressure to a greater degree than did equianesthetic concentrations of
      isoflurane. This result was attributed to a smaller effect on peripheral vascular
      resistance as compared to isoflurane and greater preservation of myocardial
      contractility as evaluated by peak positive left ventricular dP/dt and the rate
      of increase of ventricular pressure at 50 mmHg (dP/dt50) compared to other
      volatile anesthetics. Increases in diastolic coronary blood flow velocity (+19 +/
      6 and +35 +/- 12% change from control at 1.75 MAC, respectively) and concomitant
      decreases in diastolic coronary vascular resistance (-41 +/- 12 and -58 +/- 6%
      change from control at 1.75 MAC, respectively) were produced by desflurane and
      isoflurane. In the presence of autonomic nervous system blockade, the actions of
      desflurane and isoflurane were nearly identical with the exception of coronary
      vasodilation. After autonomic nervous system blockade, isoflurane increased
      coronary blood flow velocity, but desflurane did not. Furthermore, both
      desflurane and isoflurane continued to produce less depression of myocardial
      contractility than did halothane and enflurane. In summary, at equianesthetic
      concentrations, desflurane and isoflurane produced similar hemodynamic effects;
      however, in the absence of drugs that inhibit autonomic reflexes, desflurane had
      less negative inotropic activity and produced less decrease in arterial pressure.
      The coronary vasodilator actions of desflurane and isoflurane within the
      limitations of this model were not similar. When the increase in heart rate and
      rate-pressure product produced by desflurane were prevented in dogs with
      autonomic nervous system blockade, desflurane produced no change in coronary
      blood flow velocity.

PMID- 2001034
TI  - Hemodynamic effects of hydroxocobalamin in conscious dogs.
AB  - Hydroxocobalamin has been shown to be a rapid and powerful antidote in acute
      cyanide poisoning and to prevent cyanide poisoning during sodium nitroprusside
      administration. However, its hemodynamic effects remain unknown. The authors
      therefore investigated the effects in chronically instrumented conscious dogs (n
      = 8) that were randomly given hydroxocobalamin (20, 70, and 140 mg.kg-1) or
      saline. Determination of peak cobalt plasma concentrations showed that 20 and 70
      mg.kg-1 hydroxocobalamin correspond to "therapeutic doses," whereas 140 mg.kg-1
      corresponds to a supratherapeutic dose. Hydroxocobalamin did not modify heart
      rate, mean arterial pressure, left ventricular (LV) end-diastolic pressure, and
      PR and QT intervals, regardless of the dose administered. The largest dose (140
      mg.kg-1) induced a decrease in the maximum increase of LV pressure (-7 +/- 3%; P
      less than 0.05), maximum aortic blood flow acceleration (-17 +/- 5%; P less than
      0.05), and cardiac output (-19 +/- 6%; P less than 0.05), whereas systemic
      resistance increased (+41 +/- 9%; P less than 0.05). In six other dogs, local
      administration of hydroxocobalamin (0.5, 1.5, and 5.0 mg.kg-1.min-1) confirmed
      that, in large doses, this drug has direct vasoconstrictor properties affecting
      both conductance (decrease in iliac artery diameter: -2.5 +/- 0.8%) and
      resistance (decrease in iliac artery blood flow: -19.5 +/- 3.4%) vessels. Thus,
      hydroxocobalamin should be a safe cyanide antidote, considering the lack of
      hemodynamic effects within the therapeutic range of doses.

PMID- 2001035
TI  - Amrinone reverses cardiac depression and augments coronary vasodilation with
      isoflurane in the isolated heart.
AB  - Amrinone is a positive inotropic and vasodilatory agent and may be administered
      during anesthesia with isoflurane. The authors' aims were 1) to examine if
      amrinone produces coronary artery vasodilation through an increase in metabolic
      demand or through a direct vasodilatory effect or through both and 2) to test if
      amrinone attenuates cardiac depression and enhances coronary artery vasodilation
      produced with exposure to isoflurane. The effects of these drugs were examined in
      11 isolated perfused guinea pig hearts. Variables measured were: heart rate (HR),
      atrioventricular conduction time (AVCT), isovolumetric peak left ventricular
      pressure (LVP), coronary flow, percent O2 extraction, myocardial O2 consumption
      (MVO2), and the ratio of O2 delivery (DO2) to MVO2. Each heart was exposed for 10
      min periods to 10, 50, 100, and 500 microM amrinone alone, and to 0.5 or 1%
      isoflurane before, during, and after amrinone. Initial control values were: heart
      rate 216 +/- 5 beats per min; AVCT 56 +/- 1 ms; peak LVP 86 +/- 3 mmHg; coronary
      flow 6.3 +/- 0.3 ml.min-1.g-1 (11.4 +/- 0.7 ml.min-1.g-1 with adenosine bolus),
      percent O2 extraction 52 +/- 3%; DO2 107 +/- 3 microliters.min-1.g-1; MVO2 56 +/-
      4 microliters.min-1.g-1; and DO2/MVO2 1.75 +/- 0.08. Amrinone 500 microM alone
      increased (P less than 0.05) heart rate by 9%, LVP by 13%, coronary flow by 18%,
      and MVO2 by 23%; AVCT decreased by 3%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2001036
TI  - Comparison of the effects of isoflurane and desflurane on cardiovascular dynamics
      and regional blood flow in the chronically instrumented dog.
AB  - Seven mongrel dogs were chronically instrumented for the measurement of aortic
      and left ventricular blood pressures, cardiac output, left ventricular wall
      thickening, left ventricular dP/dt, and circumflex coronary, renal, hepatic and
      portal blood flows under the influence of desflurane (D) and isoflurane (I).
      Administration of the two anesthetics, was randomized, as was the order of the
      concentrations administered. Each dog was studied awake and at 1.2, 1.4, 1.75,
      and 2.0 MAC of each anesthetic on different days. Both anesthetics decreased mean
      arterial pressure, stroke volume, systemic vascular resistance, left ventricular
      dP/dt, and wall thickness. The decreases were dose-dependent for mean arterial
      pressure (percent of awake values: D 78, I 85 at 1.2 MAC, and D 67, I 69 at 2.0
      MAC); stroke volume (D 66, I 72 at 1.2 MAC, and D 52, I 57 at 2.0 MAC); dP/dt (D
      61, I 64 at 1.2 MAC, and D 46, I 49 at 2.0 MAC); and WT (D 68, I 70 at 1.2 MAC,
      and D 47, I 60 at 2.0 MAC). Systemic vascular resistance decreased approximately
      the same at 1.2 MAC (D 71, I 87%) as at 2.0 MAC (D 71, I 79%). Heart rate
      increased but also not in a dose-dependent fashion (percent of awake values: D
      177, I 145 at 1.2 MAC, and D 176, I 155 at 2.0 MAC). Coronary blood flow was
      increased by both anesthetics at all concentrations (percent of awake values: I
      136 at 1.2 MAC and 161 at 2.0 MAC of awake, and D 131 at 1.2 MAC and 138 at 2.0
      MAC.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2001037
TI  - Cerebral uptake and elimination of desflurane, isoflurane, and halothane from
      rabbit brain: an in vivo NMR study.
AB  - The authors used in vivo 19F nuclear magnetic resonance spectroscopy to determine
      rates of cerebral uptake and elimination of desflurane, isoflurane, and halothane
      in rabbits. After anesthetizing animals by intramuscular and intravenous
      injection of methohexital and inhalation of 70% nitrous oxide, intravenous and
      intraarterial catheters were inserted and a tracheostomy and craniotomy
      performed. Ventilation was controlled to maintain arterial carbon dioxide tension
      (PaCO2) from between 35 and 45 mmHg. A 2-2.5-cm diameter circle of dura was
      exposed, over which a 0.9 x 1.0-cm elliptical surface coil was placed. Cerebral
      anesthetic concentrations (CC) were estimated from spectra acquired on a 4.7
      Tesla spectrometer. Alveolar uptake and elimination also were assessed, using
      inspired (FI) and end-tidal (denoted FA0 at the end of administration)
      concentrations measured by gas chromatography. After baseline spectra were
      obtained, volatile agents were administered for 30 min, followed by a 120-min
      period of elimination. Our findings demonstrate that cerebral uptake and
      elimination correlate with solubility: they are most rapid for desflurane, next
      most rapid for isoflurane, and least rapid for halothane. During administration,
      cerebral uptake of desflurane (CC/FI = 0.690 +/- 0.049 at 9 min) was
      approximately 1.7 times faster than isoflurane (CC/FI = 0.691 +/- 0.020 at 15
      min) and 3 times faster than halothane (CC/FI = 0.662 +/- 0.040 at 27 min).
      Similarly, elimination rates for desflurane (CC/FA0 = 0.238 +/- 0.015 at 9 min)
      were 1.7 times faster than isoflurane (CC/FA0 = 0.236 +/- 0.017 at 15 min) and
      three times faster than halothane (CC/FA0 = 0.212 +/- 0.033 at 27 min).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 2001038
TI  - "Do-not-resuscitate" orders during anesthesia and surgery.

PMID- 2001039
TI  - The dynamic flexometer: an instrument for the objective evaluation of spasticity.
AB  - Anesthesiologists may care for patients who have spasticity in the operating room
      or pain clinic. A number of therapeutic modalities for treatment of spasticity
      exist, but there are few simple objective methods for evaluating their effect. We
      describe one instrument, the Dynamic Flexometer, that measures the force required
      to move the limb passively through its maximum range of motion. The data
      presented validate the instrument's reliability. Two clinical cases presented
      here demonstrate the instrument's utility. This device may be of value to
      anesthesiologists involved in the care of patients with spasticity.

PMID- 2001040
TI  - Arytenoid dislocation after tracheal intubation: an unusual cause of acute
      respiratory failure?

PMID- 2001041
TI  - Massive pulmonary embolism following tourniquet deflation.

PMID- 2001042
TI  - Hypotension during transfusion of autologous blood.

PMID- 2001043
TI  - Transient paraplegia during posterior cervical osteotomy.

PMID- 2001044
TI  - More on pharmacokinetics with a pocket calculator.

PMID- 2001045
TI  - Triple gloves.

PMID- 2001046
TI  - Complete sympathetic blockade?

PMID- 2001047
TI  - Inadvertent intraarterial placement of a sheath introducer while using the
      Raulerson syringe.

PMID- 2001048
TI  - Standard dose of conduction anesthetic is excessive for the patient with uremia.

PMID- 2001049
TI  - Reversal of blood flow in the internal jugular vein.

PMID- 2001050
TI  - Protamine: a cardiotoxic agent with negative inotropism.

PMID- 2001051
TI  - Screening for cystic fibrosis. Ethical and social issues.

PMID- 2001052
TI  - Effect of respiratory muscle fatigue on breathing pattern during incremental
      exercise.
AB  - We examined the breathing pattern during incremental exercise before and after
      induction of inspiratory muscle fatigue. Our aim was to determine whether
      induction of fatigue alters the ventilatory response to exercise and in
      particular whether such changes are most apparent at high levels of exercise when
      minute ventilation and thus inspiratory load are greatest. A group of 10 healthy
      subjects was studied on a cycle ergometer. Fatigue was achieved by having the
      subject breathe against an inspiratory threshold load that required the subject
      to generate 80% of the predetermined maximal mouth pressure to initiate airflow.
      Breathing pattern, oxygen consumption (VO2), mouth occlusion pressure (P0.1), and
      a visual analog scale (VAS) for respiratory effort were obtained for 3 min at
      rest and at 25, 50, 75, and 100% of the subject's maximal work load (Wmax) as
      determined by preliminary testing. Exercise was performed on two separate
      occasions, once immediately after induction of fatigue and the other as a
      control. Induction of fatigue had no effect on resting breathing and only minimal
      effects at the lower work loads (25 and 50% Wmax). At the higher work loads (75
      and 100% Wmax) induction of fatigue significantly altered the pattern of
      breathing during exercise. At 75% of Wmax the respiratory frequency (f) increased
      from 22.5 +/- 4.4 (SD) during control to 27.0 +/- 6.7 breaths/min (p less than
      0.02) following induction of fatigue; tidal volume was not significantly altered,
      2.15 +/- 0.65 versus 2.24 +/- 0.74 L during control. The increase in f was due to
      reductions in both inspiratory and expiratory time because fractional inspiratory
      time remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2001053
TI  - Pressure-time product during continuous positive airway pressure, pressure
      support ventilation, and T-piece during weaning from mechanical ventilation.
AB  - The objective of this study was to compare the effects of continuous positive
      airway pressure (CPAP), pressure support ventilation (PS), and T-piece on the
      pressure-time product (PTP) during weaning from mechanical ventilation. The PTP
      is an estimate of the metabolic work or oxygen consumption of the respiratory
      muscles. We studied 10 intubated patients recovering from acute respiratory
      failure of various etiologies. A modified continuous flow (flow-by) CPAP of 0 and
      5 cm H2O (CPAP-0 and CPAP-5, respectively), PS of 5 cm H2O (PS-5), and T-piece
      were applied in random order for 30 min each. In the last 5 min of the 30-min
      periods, we measured the esophageal pressure and transdiaphragmatic pressure-time
      products--PTP(es) and PTP(di), cm H2O.s/min, respectively-multiplied by
      respiratory frequency. Breathing pattern, total lung resistance (RL), quasi
      static lung compliance (CL), intrinsic positive end-expiratory pressure (PEEPi),
      end-expiratory transpulmonary pressure (Ptpexp), arterial blood gases, blood
      pressure, and heart rate were also measured. In comparison to T-piece, CPAP-5
      decreased PTP(es) 40% (p less than 0.01) and PTP(di) 43% (p less than 0.02),
      whereas PS-5 decreased PTP(es) 34% (p less than 0.01) and PTP(di) 38% (p less
      than 0.05). The decrease in PTP(es) with CPAP-5 was associated with a significant
      reduction in RL, and to a less extent in PEEPi relative to airway pressure. The
      contribution of the decrease in PEEPi to the reduction in PTP(es) amounted to
      36%. With PS-5, respiratory system mechanics and PEEPi were not significantly
      different compared with T-piece. With CPAP-0, PTP tended to be lower than with T
      piece.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2001054
TI  - Role of hypoxic drive in regulation of postapneic ventilation during sleep in
      patients with obstructive sleep apnea.
AB  - To elucidate the role of chemoresponsiveness in determining postapneic
      ventilation in sleep-disordered periodic breathing, we measured ventilatory
      response associated with apnea-induced arterial oxygen desaturation during sleep
      and compared it with the awake hypoxic ventilatory response (HVR) in 12 male
      patients with obstructive sleep apnea (OSA). Awake HVR was measured at a slight
      hypocapnic level (end-tidal PCO2 = 37 +/- 1 mm Hg, mean +/- SEM), and separately
      at a PCO2 of 45 mm Hg. During non-REM sleep both the ventilatory rate (VE) and
      the average respiratory frequency (f) in the ventilatory phase between apneic
      episodes were inversely correlated with the nadir of arterial oxygen saturation
      (nSaO2) produced by the preceding apneic phase in all patients (VE versus nSaO2;
      r = -0.74 +/- 0.03, mean +/- SEM; f versus nSaO2, r = -0.56 +/- 0.04). The
      average tidal volume (VT) also was correlated with nSaO2 in 10 of the patients (r
      = -0.56 +/- 0.05). During REM sleep VE was correlated with nSaO2 in 11 patients
      (r = -0.75 +/- 0.03, p less than 0.02). The response of VE to nSaO2 (delta
      VE/delta nSaO2) varied widely among the patients (non-REM, 0.52 to 2.16; REM,
      0.29 to 1.44 L/min/%) and was significantly lower during REM than non-REM sleep
      (p less than 0.01). The value of delta VE/delta nSaO2 during both non-REM and REM
      sleep was correlated with awake HVR at an end-tidal PCO2 of 45 mm Hg (non-REM, r
      = 0.83, p less than 0.02; REM, r = 0.76, p less than 0.05) but not with that at
      the hypocapnic level.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2001055
TI  - Tuberculosis in house staff. A decision analysis comparing the tuberculin
      screening strategy with the BCG vaccination.
AB  - The BCG vaccination is not recommended for health-care workers in the United
      States. The current strategy against tuberculosis in tuberculin-negative house
      staff is an annual tuberculin screening test followed by chemoprophylaxis with
      isoniazid for a positive result. We performed a decision analysis that
      unequivocally concluded that the BCG vaccination leads to fewer cases of
      tuberculosis in this population over a 10-yr period. The BCG vaccine requires
      only an efficacy rate of at least 13.1% to prevent more cases of tuberculosis
      than the current strategy. This threshold value is independent of the annual
      tuberculin conversion rate. This study provides a framework, based on the best
      information in the literature, on which a well-informed decision regarding
      tuberculosis prevention can be made. Therefore, this analysis demonstrates that
      the BCG vaccine should be considered for tuberculin-negative house officers and
      medical students working in high risk areas of the United States.

PMID- 2001056
TI  - Cellular immunity in current active pulmonary tuberculosis.
AB  - A group of 10 patients with recently diagnosed pulmonary TB were studied and
      compared to 10 bacillus Calmette-Guerin (BCG) immunized healthy individuals.
      Cellular immune mechanisms were explored in vitro utilizing fresh and precultured
      peripheral blood mononuclear cells exposed to PHA, PPD, and recall antigens
      (SK/SD and CA). Proliferative assays were also carried out in the presence of
      either each patient's serum (autologous serum) or cocultured with CD3(+)-depleted
      adherent cells. Serum measurements of soluble interleukin-2 (IL-2) receptor and
      synthesis of IL-2 generated by mononuclear cells stimulated with PPD and SK/SD
      were also performed. Patient sera were able to inhibit autologous as well as
      allogeneic cell responses, and a significant adherent cell suppressive effect was
      observed. As a whole the group of patients showed decreased blast transformation
      to PPD, preserved proliferative responses to other recall antigens, and a low PPD
      induced generation of IL-2. Furthermore, as possible evidence of preactivated T
      cells, these patients demonstrated high soluble IL-2 receptor serum levels. Early
      compromise of specific cell-mediated immunity, including IL-2 abnormalities, may
      be of significance in newly diagnosed pulmonary TB.

PMID- 2001057
TI  - A retrospective cohort study of the risk of tuberculosis among women of
      childbearing age with HIV infection in Zaire.
AB  - To determine the risk of active tuberculosis associated with HIV infection, we
      retrospectively studied a cohort of HIV-seropositive and HIV-seronegative women
      participating in an HIV perinatal transmission study in Kinshasa, Zaire. After a
      median follow-up of 32 months, new cases of proven pulmonary or clinically
      diagnosed tuberculosis occurred in 19 of the 249 HIV-seropositive women (7.6%,
      3.1 cases per 100 person-years) compared with 1 of the 310 HIV-seronegative women
      (0.3%, 0.12 cases per 100 person-years), for a relative risk of 26 (95%
      confidence interval, 5 to 125). Proven pulmonary tuberculosis was diagnosed in 7
      HIV-seropositive women (2.8%, 1.2 cases per 100 person-years) and 1 HIV
      seronegative woman (0.3%, 0.12 cases per 100 person-years), for a relative risk
      of 10 (95% confidence interval, 1.5 to 47). We estimated that 66 cases of proven
      pulmonary tuberculosis in 100,000 person-years of follow-up in women of
      childbearing age could be attributed to HIV; this is 35% of their estimated total
      incidence of proven pulmonary tuberculosis. Among those followed for 2 yr, 27
      (11%) of 243 HIV-seropositive women died during 2 yr of follow-up compared with
      none of 296 HIV-seronegative women (p less than 0.001). In HIV-seropositive women
      with proven or clinically diagnosed tuberculosis mortality was even higher: 5
      (26%) of the 19 HIV-seropositive women with proven pulmonary or clinically
      diagnosed tuberculosis died during follow-up compared with 22 (10%) of the 224
      HIV-seropositive women not diagnosed as having tuberculosis (relative risk 2.7;
      95% confidence interval, 1.1 to 6.3).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2001058
TI  - Adverse health effects among adults exposed to home dampness and molds.
AB  - To investigate the association between home dampness and mold and health,
      questionnaires were administered through the primary school system to parents of
      school-aged children in six regions of Canada. The present report focuses on the
      symptoms of the 14,799 adults at least 21 yr of age. The overall response rate
      was 83%, and missing values for individual variables ranged from 3 to 8%. The
      presence of home dampness and/or molds (that is, damp spots, visible mold or
      mildew, water damage, and flooding) was reported by 38% of respondents. The
      prevalence of lower respiratory symptoms (any cough, phlegm, wheeze, or wheeze
      with dyspnea) was increased among those reporting dampness or mold compared with
      those not reporting dampness or mold as follows: 38 versus 27% among current
      smokers, 21 versus 14% among exsmokers, and 19 versus 11% among nonsmokers (all p
      values less than 0.001). This association persisted after adjusting for several
      sociodemographic variables (including age, sex, and region) and several other
      exposure variables (including active and passive cigarette smoke, natural gas
      heating, and wood stoves). The odds ratio between symptoms and dampness was 1.62
      (95% confidence interval, 1.48 to 1.78) in the final model chosen. This
      association persisted despite stratification by the presence of allergies or
      asthma. Exposure to home dampness and mold may be a risk factor for respiratory
      disease in the Canadian population.

PMID- 2001059
TI  - Respiratory effects of occupational exposure in a general population sample in
      north Italy.
AB  - We assessed the effects of occupational exposure in a general population sample
      living in an unpolluted rural area of North Italy. In the age range of 18 to 64
      yr, there were 417 participants who reported any exposure to dusts, chemicals, or
      gases and 1,218 who reported no exposure. Each subject completed a standardized
      interviewer-administered questionnaire (CNR-questionnaire). A variable proportion
      of participants succeeded in performing flow-volume curves, diffusing capacity of
      carbon monoxide, and slope of alveolar plateau of nitrogen. There was no
      significant difference for symptom prevalence rates between exposed and
      nonexposed in men and women who smoke. In nonsmoking women, those exposed showed
      significantly higher prevalence rates for exertional dyspnea and asthma.
      Regarding lung function, in exposed male smokers there was a significantly higher
      slope of the alveolar plateau. In exposed female nonsmokers, FEV1 and forced
      expiratory flows were significantly lower. Multiple logistic models in the
      overall group, accounting for age, smoking, and pack-years, showed that work
      exposure was associated significantly with higher risks for all symptoms in men
      (e.g., odds ratio: 2.76 for dyspnea, 2.31 for asthma, 1.69 for cough, and 1.64
      for phlegm); in females, the association was significant for dyspnea (OR = 3.74)
      and asthma (OR = 3.29). Exposed men also had a significantly higher risk for
      %FEV1 or FEV1/FVC% below 70 (OR = 1.45). Our findings confirm those of the other
      few epidemiologic surveys in general population samples and contribute to the
      suggestion of a causal association between occupational exposure and chronic
      obstructive pulmonary disease.

PMID- 2001060
TI  - Acceptability and reproducibility criteria of the American Thoracic Society as
      observed in a sample of the general population.
AB  - An analysis of spirograms of 6,486 subjects from the general population, ages 8
      to 90, was conducted to determine their ability to satisfy the American Thoracic
      Society's (ATS) acceptability and reproducibility criteria. The results indicate
      that both older and younger subjects had more difficulty satisfying the ATS
      acceptability and reproducibility criteria. The difficulty in satisfying the ATS
      reproducibility criterion, particularly in younger subjects, was in part
      associated with their smaller heights and lung volumes. A relatively uniform
      within-subject variability of FVC and FEV1 in terms of the mean differences
      between the largest and second largest FVC and FEV1, for all heights, was
      observed. In addition, unlike the ATS reproducibility criterion, when a constant
      200-ml reproducibility criterion for FVC and FEV1 was used, there was no longer a
      significant difference between the number of reproducibility criterion failures
      for the 14 different height groups used. These results suggest that the ATS
      reproducibility criterion, based on a percentage of the FVC and FEV1, may
      inappropriately classify a higher percentage of subjects with smaller heights and
      lung volumes as having a nonreproducible test. In contrast, subjects with larger
      heights and lung volumes are much less likely to fail the ATS reproducibility
      requirement. These results emphasize the importance of following the ATS
      recommendation of using the reproducibility criterion only as a goal during data
      collection, not to classify a subject as having an invalid test.

PMID- 2001061
TI  - Effects of nitrogen dioxide exposure on pulmonary function and airway reactivity
      in normal humans.
AB  - Nitrogen dioxide (NO2) is a product of combustion that has become recognized as a
      significant component of indoor air in some homes. Despite extensive study, it
      remains unresolved whether exposures to low levels of NO2 affect airway function
      or reactivity. These studies were designed to assess effects of various levels
      and patterns of NO2 exposure on pulmonary function and airway reactivity in
      normal humans. Normal volunteers screened for the absence of airway
      hyperreactivity were exposed for 3 h in an environmental chamber to purified air
      or NO2, separated by at least 2 wk, according to three protocols: (1) continuous
      0.60 ppm NO2, (2) baseline 0.05 ppm NO2 with intermittent peaks of 2.0 ppm, and
      (3) continuous 1.5 ppm NO2. Subjects exercised for 10 min of each 30 min at a
      level sufficient to result in a minute ventilation near 40 L/min. Pulmonary
      function was measured before, during, and after exposure. Airway reactivity to
      increasing doses of carbachol was assessed 30 min after exposure. NO2 did not
      directly alter pulmonary function in any of the exposure protocols. In addition,
      airway reactivity was not altered by continuous exposure to 0.60 ppm or
      intermittent peaks of 2.0 ppm NO2. In contrast, continuous exposure to 1.5 ppm
      NO2 resulted in a greater fall in FVC and FEV1 in response to carbachol than
      after exposure to air (percent decrease in FVC: 1.5% after air, 3.9% after NO2, p
      less than 0.01). We conclude that for subjects without airway hyperreactivity,
      exposure to 1.5 ppm NO2 for 3 h increases airway reactivity, whereas repeated 15
      min exposures to 2.0 ppm NO2 do not alter airway reactivity.

PMID- 2001062
TI  - Is the clinical history a satisfactory means of diagnosing occupational asthma?
AB  - In some countries a diagnosis of occupational asthma for medicolegal purposes is
      made when a questionnaire is suggestive and the individual is exposed to a
      product known to be a sensitizer. The value of an open questionnaire administered
      by physicians with experience in occupational asthma is unknown, however. We
      prospectively assessed all subjects (162) referred to our clinic because their
      physicians thought their asthma might be work related. The medical questionnaire
      included questions about the nature of the symptoms (dyspnea, wheezing, cough,
      and chest tightness) and the timing (worse at work or after a shift at work or
      improved during weekends or holidays). An initial clinical assessment was set by
      the physician on a scale that ranged from highly probable to probable, uncertain,
      unlikely, or absent. Subjects then underwent objective assessment with specific
      inhalation challenges (n = 72), serial monitoring of peak expiratory flow rates
      for periods at work and away from work (n = 29), or both (n = 61), to confirm or
      rule out the diagnosis of occupational asthma. A total of 75 subjects (46%) were
      shown to have occupational asthma. Symptoms alone (type and timing) did not
      provide a satisfactory differentiation between those subjects with and those
      without occupational asthma. For example, 66 of 75 (88%) subjects with
      occupational asthma said that their symptoms improved during holidays, but 66 of
      87 (76%) subjects without occupational asthma experienced a similar
      improvement.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2001063
TI  - Dynamic T-cell changes in peripheral blood and bronchoalveolar lavage after
      antigen bronchoprovocation in asthmatics.
AB  - We previously demonstrated decrease of peripheral blood CD4+ cells 48 to 72 h
      after antigen-induced bronchoprovocation in asthmatic subjects. To determine if
      this was accompanied by reciprocal changes in bronchoalveolar lavage (BAL) fluid,
      we sampled BAL before and 48 h after antigen administration. Peripheral blood
      lymphocytes (PBL) and BAL T-cell subset composition were examined in eight
      extrinsic asthmatics during three different weeks. During control week (CW) BAL
      was preformed at baseline, and PBL subsets were followed for 3 days. During
      placebo week (PW) a placebo inhalation was followed by a BAL at 48 h and daily
      PBL for 3 days. Asthmatic attacks were induced by inhalation of a relevant
      antigen at the start of antigen week (AW) and followed by examining the BAL at 48
      h and PBL daily for 72 h. We found that BAL as a stimulus had no effect on T-cell
      composition of the PBL after the procedure. After induction of an asthmatic
      attack there was a reduction of PBL CD4+ cells from a baseline mean of 52.6% to
      38.8% at 48 h (p less than 0.05). At the same time BAL CD4+ cells increased from
      35.6% at PW to 47.3% in AW (p less than 0.05). These data are compatible with
      specific recruitment of PBL CD4+ cells into the respiratory system in atopic
      subjects undergoing antigenic bronchoprovocation.

PMID- 2001064
TI  - Cultured peripheral blood mononuclear cells derived from patients with acute
      severe asthma ("status asthmaticus") spontaneously elaborate a neutrophil
      chemotactic activity distinct from interleukin-8.
AB  - Peripheral blood mononuclear cells (PBMC) isolated from patients with acute
      severe asthma on the day of admission to hospital were cultured in vitro in serum
      free medium in the absence of mitogenic stimulants for as long as 72 h. PBMC
      isolated from control groups (mild asthma, chronic obstructive airway disease,
      normal subjects) were cultured in a similar fashion. After incubation, the
      culture supernatants were tested for neutrophil chemotactic activity (NCA) using
      a modified Boyden chamber technique. PBMC from patients with acute severe asthma
      elaborated significantly greater amounts of NCA into the culture supernatants as
      compared with all three control groups (p less than 0.01). The amounts of PBMC
      derived NCA from the same patients after 7 days of hospital therapy and clinical
      improvement were reduced (p less than 0.01). A correlation was observed between
      the extent of reduction in spontaneous release of NCA by PBMC derived from
      patients with acute severe asthma and the degree of clinical improvement of their
      asthma (p less than 0.02). Both monocytes and lymphocytes, when cultured
      separately, released NCA in amounts sufficient to account for the total activity
      released by unfractionated PBMC. NCA in PBMC culture supernatants accumulated
      progressively with time, a process inhibited in a dose-dependent fashion by
      cycloheximide. The amounts of NCA in culture supernatants did not correlate with
      the concentrations of histamine in lysates of the PBMC prepared just prior to
      culture.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2001065
TI  - Human nasal glandular secretion of novel antioxidant activity: cholinergic
      control.
AB  - Exposure of the respiratory mucosa to oxygen-enriched air contributes to the
      generation of the lung damage in both adult respiratory distress syndrome and
      bronchopulmonary dysplasia. Recent work has identified the nasal submucosal gland
      as the source of diverse molecules important in mucous membrane host defense. We
      searched for the presence of antioxidant activity in nasal glandular secretions,
      the absence of which could possibly predispose to oxygen-induced injury.
      Employing a low molecular weight preparation of nasal secretions (a pooled
      concentrate passed over a 10,000-dalton molecular sieve), antioxidant activity
      capable of inhibiting both horseradish peroxidase and Fenton reagent reactions
      was discovered. The following lines of evidence suggest that submucosal glands
      are the source of this activity. (1) Antioxidant activity present in resting,
      baseline nasal washings is significantly increased after cholinergic stimulation
      either in response to topical methacholine or induced by a gustatory reflex. (2)
      Application of atropine reduced the antioxidant activity to baseline levels after
      either of the cholinergic stimuli. (3) Levels of antioxidant activity correlated
      very closely with the secretion of lactoferrin, a recognized product secreted
      solely from the serous cell of the submucosal gland. The antioxidant activity is
      due to novel, previously unrecognized molecules. This activity is found in nasal
      secretions containing molecules less than 10,000 daltons, is unaffected by N
      ethyl maleimide (which inactivates glutathione, another low molecular weight
      antioxidant), is not associated with the capacity to reduce cytochrome c (as seen
      with ascorbic acid), and resides in the water soluble pool of secretions (in
      contrast to vitamin E, another putative antioxidant).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 2001066
TI  - Effects of zymosan-activated human granulocytes on isolated human airways.
AB  - In asthma a temporal association exists between the late allergic reaction (LAR),
      the influx of granulocytes into the airway wall, and an increase in bronchial
      responsiveness. We therefore tested the hypothesis that activated human
      granulocytes constrict isolated human airways and increase their sensitivity to
      cholinergic stimuli. Bronchial rings were dissected from 23 lung tissue specimens
      collected at thoracotomy and studied isotonically in organ baths. Airways were
      incubated with 1, 2, 5, 10, or 20 x 10(6) granulocytes from normal or atopic
      donors. Activation of the cells with serum-treated zymosan (STZ, 0.2 mg/ml),
      which itself did not alter baseline airway caliber, resulted in a
      bronchoconstriction proportional to the number of zymosan-activated granulocytes
      (ZAG) present (rs = 0.79, p less than 0.001). This contraction was reduced by
      about 70% with the leukotriene C4/D4 receptor antagonist FPL 55712 (11.5 microM;
      p less than 0.001) or with the lipoxygenase inhibitor nordihydroguaiaretic acid
      (10 microM; p less than 0.001). The scavengers of activated oxygen molecules
      superoxide dismutase (300 U/ml) and bovine catalase (5,000 U/ml), the
      cyclooxygenase inhibitor indomethacin (10 microM), or the histamine (H1) receptor
      antagonist mepyramine (2.8 microM) had no effect. Granulocyte suspensions from
      atopic donors contained more eosinophils (p less than 0.001), and the magnitude
      of the contraction to 10 x 10(6) ZAG was related to the proportion of eosinophils
      (rs = 0.66, p less than 0.01). The sensitivity of the airways to methacholine was
      unchanged in the presence of 1, 2, or 5 x 10(6) ZAG and decreased with 10 or 20 x
      10(6) ZAG (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2001067
TI  - Inhaled furosemide prevents both the bronchoconstriction and the increase in
      neutrophil chemotactic activity induced by ultrasonic "fog" of distilled water in
      asthmatics.
AB  - Inhaled furosemide has been shown to prevent bronchoconstriction induced by
      inhalation of ultrasonic nebulization of distilled water (UNDW) in bronchial
      asthma. To evaluate whether inhaled furosemide also prevents the increase in
      serum neutrophil chemotactic activity (NCA) observed during UNDW
      bronchoconstriction, we measured NCA during UNDW challenge without (control) and
      immediately after inhalation of furosemide (40 mg) or placebo (saline) in 10
      asthmatics responsive to UNDW, in a randomized, double-blind study. NCA was
      assessed by measuring the maximal distance reached by neutrophils in a filter
      when challenged with the subject serum in a Boyden chamber ("leading front").
      UNDW inhalation produced a significant increase in NCA in each subject. Gel
      filtration chromatography on S400 column indicated that the NCA released were 600
      to 700 kD. Saline had no effect on bronchoconstriction nor on NCA increase
      induced by UNDW in nine patients. Furosemide did not change baseline FEV1, but it
      prevented bronchoconstriction and NCA increase in nine patients. In the whole
      group the maximal decrease in FEV1 after UNDW was -31.1%, SEM 4.7 after saline
      and -7.5%, SEM 5.2 after furosemide, p less than 0.001, the maximal increase in
      NCA after UNDW was +52.9%, SEM 9.2 after saline and +3.8%, SEM 3.1 after
      furosemide, p = 0.001. These results indicate that inhaled furosemide prevents
      both the bronchoconstriction and the NCA increase induced by UNDW inhalation in
      most asthmatic patients. This finding adds support to the suggestion that
      furosemide acts on mast cells.

PMID- 2001068
TI  - Antigen-induced release of airway epithelium-derived inhibitory factor.
AB  - The ability of guinea pig trachea to produce a vasoactive epithelium-derived
      inhibitory factor (EpDIF) in response to mast cell-derived mediators was assessed
      in a coaxial bioassay system. The mast cell degranulating agent compound 48/80
      (10 micrograms/ml) and histamine caused reductions in phenylephrine-induced tone
      in endothelium-denuded rat aorta preparations mounted coaxially within epithelium
      intact guinea pig tracheal tube tissue. Relaxation responses to histamine and to
      compound 48/80 (10 micrograms/ml) were markedly reduced in the presence of
      mepyramine (50 microM) or when the epithelium was removed from coaxially mounted
      guinea pig trachea, indicating that they were mediated via the release of EpDIF.
      Coaxial bioassay assemblies were also prepared using EpDIF donor tracheal tissue
      obtained from guinea pigs actively sensitized to ovalbumin. Subsequent challenge
      with ovalbumin (10(-7) to 10(-1) mg/ml) produced concentration-dependent
      relaxation mediated by EpDIF. Ovalbumin-induced relaxation responses were not
      inhibited in the presence of either mepyramine (20 and 100 microM) or SKF 104353
      Z2 (10 microM) alone but were significantly reduced when both mepyramine (20
      microM) and SKF 104353-Z2 (10 microM) were present. Antigen-induced relaxation
      was apparently mediated by EpDIF in response to mast cell-derived histamine and
      leukotrienes. Rat tracheal airway smooth muscle did not relax in response to
      EpDIF, suggesting selectivity of action on vascular smooth muscle. Vasoactive
      EpDIF may play a role in protecting against antigen-induced bronchoconstriction
      by regulating bronchial circulation flow.

PMID- 2001069
TI  - Effects of repetitive bolus injections of zymosan-activated plasma on lung
      mechanics and airway responsiveness in awake sheep.
AB  - We studied the pulmonary effects of repetitive bolus injections of autologous
      zymosan-activated plasma (ZAP) in nine chronically instrumented awake sheep.
      Aerosol histamine responsiveness was determined 1 h before and 4.5 h after the
      first bolus injection of ZAP. Each sheep received in the pulmonary artery a total
      of eight 5-ml bolus injections of ZAP separated by 30 min. On a separate day,
      with the order of experimentation varied to avoid sequential bias, six of the
      nine sheep also received "control" plasma (plasma prepared in the identical
      fashion as ZAP but not incubated with zymosan). "Control" plasma caused
      reproducible transient increases in pulmonary artery pressure, but it did not
      cause alterations in any of the other measured variables. Repetitive bolus
      injections of ZAP caused reproducible alterations in lung mechanics, pulmonary
      hemodynamics, lung fluid and solute exchange, oxygenation, and peripheral
      leukocyte counts. The increases in thromboxane-B2 concentrations in lung lymph
      and plasma were greatest after the first bolus injection of ZAP, with the
      magnitude of these changes diminishing on succeeding injections of ZAP. Aerosol
      histamine responsiveness did not increase after the eight bolus injections of
      ZAP.

PMID- 2001070
TI  - Role of pulmonary inflammation in altered airway responsiveness in three sheep
      models of acute lung injury.
AB  - Pulmonary inflammation may contribute to increased airway responsiveness in
      experimental models of acute lung injury. Infusions of endotoxin, phorbol
      myristate acetate (PMA), or zymosan-activated plasma (ZAP) all result in the
      accumulation of polymorphonuclear leukocytes (PMNs) in the lung and alterations
      in lung mechanics. These three interventions have strikingly different effects on
      airway responses to aerosol histamine: ZAP does not increase airway
      responsiveness, whereas endotoxin causes a greater increase in airway
      responsiveness than does PMA. The present histologic study examines the question
      of whether the pattern and severity of PMN and mast cell accumulation in large-
      and medium-sized airways and lung periphery could contribute to the differences
      in airway responsiveness to histamine. Minimally instrumented sheep were given
      either an infusion of endotoxin (0.5 microgram/kg over 20 min), a bolus injection
      of PMA (5 micrograms/kg), or repetitive boluses of autologous ZAP (5 ml). Four
      and a half hours later, the animals were killed, and the left lung was removed
      and fixed in the distended state. Three levels of the left lung were examined by
      light microscopy: the large hilar bronchus, a medium-sized bronchus, and
      peripheral lung. The number of PMNs and mast cells in the airway wall were
      expressed as cells/mm length of airway circumference and in the lung periphery as
      cells/100 alveolar profiles. Both endotoxin and PMA caused a significant 2- to 3
      fold increase in number of PMNs/mm of large airway circumference, the majority of
      PMNs being in the blood vessels of the lamina propria and submucosa; ZAP caused
      only minimal PMN accumulation in the blood vessels of the submucosa.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 2001071
TI  - Plasma levels of tumor necrosis factor in the adult respiratory distress
      syndrome.
AB  - The purpose of the study was to evaluate the role of tumor necrosis factor alpha
      (TNF alpha) in the pathogenesis of acute lung injury in critically ill patients.
      An immunoradiometric assay with an upper normal limit of 9 pg/ml was used to
      measure plasma TNF alpha levels (pl-TNF alpha) in 34 patients with adult
      respiratory distress syndrome (ARDS) and in 16 patients in whom, despite the
      presence of risk factors, ARDS did not develop. Pl-TNF alpha was elevated in 76%
      of the patients with ARDS (71 +/- 104 pg/ml) and in 48% of the at-risk patients
      (47 +/- 73 pg/ml); the difference between the two groups was not statistically
      significant. In 13 patients studied serially from the onset (Day 0) to the fifth
      day of ARDS, the peak pl-TNF alpha occurred later than Day 0 in seven subjects.
      Although the highest pl-TNF alpha levels were found in septic patients,
      moderately elevated values were also observed in 56% of nonseptic subjects. We
      conclude that plasma TNF alpha level is not a marker of ARDS but rather of shock
      and sepsis. These results do not exclude a pathogenic role of TNF alpha in acute
      lung injury since this cytokine could be produced and exert its effects within
      the lungs. The large incidence of abnormally high could be produced and exert its
      effects within the lungs. The large incidence of abnormally high plasma TNF alpha
      levels raises important questions on the role of this toxic cytokine in other
      disorders occurring in critically ill patients.

PMID- 2001072
TI  - Increased TNF-alpha secretion by alveolar macrophages from patients with
      rheumatoid arthritis.
AB  - Tumor necrosis factor alpha (TNF) and interleukin-1 (IL-1) production by alveolar
      macrophages (AM) was evaluated in 17 rheumatoid arthritis (RA) patients without
      interstitial lung disease (ILD, Group 1) and 14 RA patients with clinical ILD
      (Group 2) in comparison with 10 control subjects. AM after recovery by
      bronchoalveolar lavage were selected by adherence, and then supernatants were
      collected after 3 or 24 h of culture. Results showed no modification of IL-1
      synthesis in either group of RA patients. Spontaneous TNF production was
      significantly increased in Group 2 (2.5 +/- 0.5 ng/ml) as well as in Group 1 (2.4
      +/- 0.4 ng/ml) compared with control subjects (0.43 +/- 0.1 ng/ml, p less than
      0.001). In addition, AM from patients untreated or treated exclusively by
      nonsteroidal antiinflammatory drugs produced similar levels of TNF, whereas those
      receiving corticosteroids, second-line drugs (such as sulfasalazine,
      aurothiomalate, and methotrexate), or the combination of both therapy regimens
      released significantly less TNF. Interestingly, TNF was not different in both
      groups, but Group 2 had a markedly increased ratio of local immune complex to
      albumin in bronchoalveolar lavage fluid (0.47 +/- 0.12 versus 0.07 +/- 0.02 in
      Group 1; p less than 0.002). TNF thus appears an additional component of RA
      subclinical alveolitis in RA, but its prognostic value and its precise role in
      lung damage remain to be determined. Development of ILD requires certainly
      complex interactions of synergistic factors, possibly including local immune
      complexes detected in BAL fluids.

PMID- 2001073
TI  - Group B streptococcus induces tumor necrosis factor in neonatal piglets. Effect
      of the tumor necrosis factor inhibitor pentoxifylline on hemodynamics and gas
      exchange.
AB  - Group B streptococcus (GBS), a common neonatal gram-positive pathogen, causes
      similar pathophysiologic features in human newborns and neonatal animal models of
      sepsis. Previous reports suggest that mediators in addition to TxA2 and PGI2
      contribute to the late effects of GBS infusion (2 to 4 h), which include
      persistent increases in Ppa, hypoxemia, systemic hypotension, and a progressive
      fall in CO. Tumor necrosis factor (TNF) infusion in animals produces several of
      the late GBS effects. We hypothesized that GBS causes increased serum TNF levels
      2 to 4 h into infusion in neonatal piglets. We also postulated that the TNF
      inhibitor, pentoxifylline (PTF), would attenuate both GBS-induced TNF production
      and late GBS effects. In piglets infused with 1.25 x 10(9) cfu/kg/h of GBS, serum
      TNF levels (pg/ml, ELISA assay) significantly increased at 2 h (231 +/- 41) and
      at 4 h (1,047 +/- 290, n = 9). In piglets infused with concomitant GBS + PTF,
      serum TNF levels at 4 h (208 +/- 39, n = 8) were reduced compared to GBS alone
      piglets (p less than 0.02). Control piglets infused with 0.9% saline or PTF alone
      for 4 h had no detectable serum TNF (less than 35). GBS alone and GBS + PTF
      infusion caused similar increases in serum TxB2 levels at 1, 2, and 4 h. Serum 6
      keto-PGF1 alpha levels (pg/0.1 ml) significantly increased at 4 h (85 +/- 18)
      with GBS alone, and were more elevated at 4 h (306 +/- 75) with GBS + PTF
      infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2001074
TI  - Corticosteroid inhibition of airway microvascular leakage.
AB  - We studied the effect of dexamethasone on microvascular leakage (using Evans blue
      dye as a marker of plasma exudation) induced in rat airways by platelet
      activating factor (PAF). Intravenously administered PAF caused a dose-related
      increase in plasma leakage over the range 0.1 to 1 micrograms/kg. At 500 ng/kg
      PAF, the response was maximal in the extrapulmonary airways examined with
      increases in leakage above those in control animals of 312% in the larynx, 295%
      in the trachea, and 167% in the main bronchi. A maximal response was not achieved
      in the intrapulmonary airways at the doses of PAF tested: at 1 microgram/kg the
      increase was 206% above that in control animals. Dexamethasone, given by
      intraperitoneal injection 24 h and 4 h before PAF at a dose of 0.2 mg/kg on each
      occasion, partially inhibited leakage induced by PAF (1 microgram/kg) in all
      airway levels studied by 43 to 65%. At each level the tissue concentration of dye
      was reduced to a value that was significantly (p less than 0.05) different from
      either PAF or control values. We also determined whether a high dose (8 mg/kg) of
      dexamethasone given intraperitoneally would inhibit plasma leakage of dye induced
      by either PAF or antigen-challenge of sensitized rats. When given 4 h before
      antigen, dexamethasone completely prevented allergen-induced leakage in the
      airways showing significant leakage (larynx, trachea, and intrapulmonary
      airways). Similarly, dexamethasone (4 h before) partially inhibited PAF-induced
      leakage in the trachea and main bronchi. In summary, in rat airways, both low and
      high doses of dexamethasone markedly inhibit mediator-induced plasma
      exudation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2001075
TI  - Fibrinogen depletion and control of permeability in oleic acid lung injury.
AB  - To determine if the biphasic pulmonary clearance of aerosolized 99mTc diethylene
      penta acetate (99mTc-DTPA) observed in oleic acid lung injury represents acute
      epithelial damage followed by sealing as a result of intra-alveolar fibrin
      deposition, we examined the effect of fibrinogen depletion. 99mTc-DTPA clearance
      was assessed in three groups of rabbits: Group 1, normal fibrinogen + oleic acid
      injury; Group 2, fibrinogen-depleted + oleic acid injury; Group 3, fibrinogen
      depleted with no oleic acid injury. In Group 3 animals with no lung injury, the
      99mTc-DTPA clearance rate, expressed as k, the percent decrease in thoracic
      radioactivity, was similar to that previously reported for healthy rabbits (k =
      1.16 +/- 0.57%/min, mean +/- SD). Oleic acid administration to Groups 1 and 2
      resulted in significantly faster clearance rates, with identical biphasic curves
      in all animals, irrespective of fibrinogen status. There were no significant
      differences between either the initial fast phase (k, Group 1 = 5.26 +/-
      1.83%/min, Group 2 = 5.70 +/- 1.77%/min) or the subsequent slow phase (k, Group 1
      = 1.67 +/- 0.63%/min, Group 2 = 1.57 +/- 0.55%/min, p greater than 0.05). On
      histologic examination, Groups 1 and 2 showed greater cellular interstitial
      infiltrate, alveolar edema, and hemorrhage than did Group 3. Fibrinogen depletion
      plus oleic acid injury resulted in greater alveolar cellular exudate, edema, and
      hemorrhage than did either oleic acid or fibrinogen depletion alone. We conclude
      that fibrinogen is not necessary to produce biphasic 99mTc-DTPA clearance in
      oleic acid lung injury.

PMID- 2001076
TI  - Quantifying lung structure. Experimental design and biologic variation in various
      models of lung injury.
AB  - The lung is a complex organ composed of a large number of different cell types of
      varying size and shape. Quantification of lung structure requires an
      understanding of how the distribution of specific cells and their characteristics
      affect the accuracy of measurement made on them and how to optimize experimental
      design for a morphometric study. We have studied lung structural modifications in
      a variety of lung injuries over the last decade. Extensive quantitative data from
      EM morphometric studies of pulmonary tissue have been collected. These data
      provide a unique opportunity to study the accuracy and efficiency of methods used
      to quantitate lung structure. We present and discuss novel computation-intensive
      methods for the estimation of biologic variability, sampling error, and
      measurement error. A new concept, unnested analysis of variance for stratified
      sampling and the use of computer-based methods for statistical analysis (the
      bootstrap method) and optimizing experimental design (nonlinear minimization
      procedure) are described in this report. Examples of experimental designs with
      their corresponding levels of accuracy and cost are also provided. The number of
      samples needed for a given level of precision is affected by the volume density
      of the structure being measured. The most important determinant for the overall
      accuracy of a morphometric study is the number of animals studied. Biologic
      variations between samples within an animal and among animals can vary
      significantly as a function of the model of injury studied.

PMID- 2001077
TI  - Bronchial mucus hypersecretion in acute quadriplegia. Macromolecular yields and
      glycoconjugate composition.
AB  - In acute quadriplegia we have noted that about one in five patients develops
      unexplained production of markedly excessive and tenacious bronchial mucus.
      Spontaneous recovery from mucus hypersecretion usually occurs within weeks to
      months. Mucus samples collected from 12 patients have been found to be abnormal.
      Macromolecular contents of single aspirates yielded as much as 500 mg. Analytical
      ultracentrifuge analysis showed the mucus to contain considerable epithelial
      glycoprotein (GP) of typical buoyant density; its amino acid and carbohydrate
      compositions were characteristic of the GP from hypersecretory bronchial mucus
      such as in chronic bronchitis and cystic fibrosis. In five patients studied after
      recovery from hypersecretion, there tended to be relatively less GP. The mucus
      samples contained a high density glycoconjugate (GC): this had sugars of GP but
      also reacted positively with a monoclonal antibody to keratan sulfate. Its amino
      acid composition was different from that of GP: threonine was lower and glycine
      was higher than in GP. In mucus from one patient who died, chondroitin sulfate
      ABC and hyaluronic acid were identified as well. This suggests proteoglycans are
      involved in the pathophysiology of mucus hypersecretion. The sudden onset and
      spontaneous recovery of hypersecretion suggests that it is not due to gland
      hypertrophy. We speculate that in acute quadriplegia it is due to disturbed
      neuronal control of bronchial mucus gland secretion, perhaps related to initial
      disappearance and later reappearance of peripheral sympathetic nervous system
      tone.

PMID- 2001078
TI  - Panlobular emphysema in young intravenous Ritalin abusers.
AB  - We studied a distinctive group of young intravenous Ritalin abusers with profound
      obstructive lung disease. Clinically, they seemed to have severe emphysema, but
      the pathologic basis of their symptoms had not been investigated previously.
      Seven patients have died and been autopsied: in four, the lungs were fixed,
      inflated, dried, and examined in detail radiologically, grossly, microscopically,
      and by electron probe X-ray microanalysis. All seven patients had severe
      panlobular (panacinar) emphysema that tended to be more severe in the lower lung
      zones and that was associated with microscopic talc granulomas. Vascular
      involvement by talc granulomas was variable, but significant interstitial
      fibrosis was not present. Five patients were tested for alpha-1-antitrypsin
      deficiency and found to be normal, as were six similar living patients. These
      findings indicate that some intravenous drug abusers develop emphysema that
      clinically, radiologically, and pathologically resembles that caused by alpha-1
      antitrypsin deficiency but which must have a different pathogenesis. Talc from
      the Ritalin tablets may be important, but the mechanism remains to be elucidated.

PMID- 2001079
TI  - Rate of oxyhemoglobin desaturation in obstructive versus nonobstructive apnea.
AB  - Preapneic thoracic gas volume (Vtg), arterial saturation (SaO2), and mixed venous
      oxygen saturation (SvO2), have been shown to influence the rate of SaO2 fall
      (dSaO2/dt) during apnea. We asked the following question: does tissue oxygen
      consumption (tVO2) affect the dSaO2/dt during apnea? We attempted to answer this
      question by comparing dSaO2/dt during obstructive apneas (high tVO2) with
      dSaO2/dt during nonobstructive apneas (low tVO2) in six adult baboons. Fiberoptic
      central venous and arterial catheters were used for continuous monitoring of
      SvO2, SaO2, and cardiac output. A sapphire-bearing turbine monitored minute
      ventilation and airflow cessation. A Respitrace and esophageal pressures were
      used to assess relative differences in Vtg. Obstructive apneas (30, 45, and 60-s)
      were created by clamping an indwelling cuffed endotracheal tube at end
      expiration. Nonobstructive apneas were created by paralyzing the animals with
      atracurium and interrupting ventilation for periods equivalent to those of the
      obstructed apneas. The ventilator was adjusted to duplicate the respiratory rate,
      tidal volume, and relative Vtg of the spontaneously breathing animal. Mean tVO2
      during spontaneous breathing was 110 ml/min (Fick method) and decreased to 90
      ml/min during paralysis (p less than 0.05). The dSaO2/dt for the three apnea
      durations (mean, all animals), obstructive versus nonobstructed were: 0.85 and
      0.74%/s (n = 6), 0.87 and 0.75%/s (n = 6), and 0.60 and 0.48%/s (n = 4),
      respectively. The dSaO2/dt was significantly lower during the nonobstructive
      apneas. We conclude that differences in VO2 during apnea may affect the dSaO2/dt
      and that for the same duration apnea, central apneas may show less desaturation
      than obstructive apneas where vigorous muscular efforts at overcoming obstruction
      are common.

PMID- 2001080
TI  - Acute respiratory failure caused by pulmonary vasculitis after L-tryptophan
      ingestion.
AB  - This report describes two women who presented with severe respiratory failure and
      diffuse pulmonary infiltrates in the fall of 1989. Both required prolonged
      assisted ventilation because of severe shunt physiology. Open lung biopsies on
      admission revealed a small vessel vasculitis as the sole morphologic abnormality
      in both patients. Both responded to high dose corticosteroids. Neither patient
      exhibited evidence of systemic vasculitis, and neither had serologic evidence of
      an immune disorder. Common to both patients was ingestion of L-tryptophan. One
      patient exhibited several features of the eosinophilia-myalgia syndrome. The
      other patient did not appear to have the syndrome, but the temporal relationship
      between the onset of symptoms and initiation of L-tryptophan treatment was
      striking. The presentation of these patients alters our notions concerning the
      spectrum of clinical manifestations caused by this agent, and the response to
      methylprednisolone supports its efficacy in the treatment of this disorder.

PMID- 2001081
TI  - The do-not-resuscitate order. Ethical and legal imperative or medical decision?
AB  - Cardiopulmonary resuscitation (CPR), widely used in United States hospitals,
      results in long-term survival that averages about 15%. The patient has the
      ethical and legal right to reject CPR. Avoidance of CPR when death is
      anticipated, or when the patient does not wish resuscitation, requires the
      writing of a do-not-resuscitate order. Cardiopulmonary resuscitation has the
      risks of trauma, residual impairment if incompletely successful, and prolongation
      of dying. Like any other medical treatment, CPR should only be administered if it
      is expected to confer lasting benefit to the patient. If CPR does not offer even
      a modicum of lasting benefit, it is not medically appropriate to administer the
      treatment, and the physician may write a do-not-resuscitate order. The rationale
      for writing the order should be documented, and the patient and family should be
      informed of the treatment decision. Hospital regulations regarding the writing of
      DNR orders should reflect this approach. Experience to date indicates that there
      is minimal risk of malpractice or criminal action in relation to writing do-not
      resuscitate orders.

PMID- 2001082
TI  - Oxygen supply and utilization relationships. A reevaluation.
AB  - The relationship between oxygen transport (TO2) and oxygen consumption (VO2) has
      been studied in patients with a number of acute and chronic disorders. Many of
      these patients have been shown to have a linear relationship between these two
      variables over a wide range of TO2, which has been considered as evidence of
      pathologic supply dependency. This supply dependency contrasts with animal
      studies that have clearly demonstrated a biphasic relationship between TO2 and
      VO2. This review of the available data concerning the relationship between oxygen
      transport and supply under conditions of increased oxygen requirements and
      reduced oxygen transport suggests the possibility that the observed interaction
      in patients may, in many cases, represent the normal physiologic behavior of the
      system rather than an abnormal manifestation of impaired oxygen extraction.

PMID- 2001083
TI  - NHLBI Workshop summary. Current concepts in idiopathic pulmonary fibrosis: a road
      map for the future.

PMID- 2001084
TI  - The effect of repetitive exercise on airway temperatures.

PMID- 2001085
TI  - Electrophysiological investigation of respiratory muscles.

PMID- 2001086
TI  - Interferon-alpha produces sustained cytogenetic responses in chronic myelogenous
      leukemia. Philadelphia chromosome-positive patients.
AB  - OBJECTIVES: To evaluate the frequency and the course of complete cytogenetic
      responses in interferon-alpha (IFN-alpha)-treated patients with chronic
      myelogenous leukemia. DESIGN: Two prospective trials in consecutive patients.
      SETTING: A major tertiary cancer center. PATIENTS: Ninety-six consecutive
      patients with chronic myelogenous leukemia with disease duration of less than 1
      year. INTERVENTION: Patients received partially pure IFN-alpha intramuscularly,
      from 3 to 9 million U/d (51 patients) or recombinant IFN-alpha 2a (Roferon,
      Hoffmann-LaRoche, Inc., Nutley, New Jersey), 5 million U/m2 body surface area
      daily (45 patients). MEASUREMENTS: Hematologic and cytogenetic tests were
      administered. MAIN RESULTS: Seventy of the patients (73%) achieved hematologic
      remission (95% CI, 63% to 81%), and 18 (19%) had complete suppression of the
      Philadelphia chromosome on at least one cytogenetic test. A complete cytogenetic
      response was induced in 7 of 51 or 14% (CI, 6% to 26%) of the patients treated
      with the partially pure IFN-alpha and in 11 of 45 or 24% (CI, 13% to 40%) of the
      patients treated with recombinant IFN-alpha 2a. The difference in complete
      cytogenetic response between the two groups was 10.7% (CI, - 5% to 26%; P greater
      than 0.2). Eleven patients had durable, ongoing, complete cytogenetic responses
      from 6 to more than 45 months (median, more than 30 months). CONCLUSION: This
      study was the first to show sustained, complete cytogenetic responses in a subset
      of patients with chronic myelogenous leukemia treated with single-agent therapy.
      The nature of this remission, that is, whether it depends on continuous therapy,
      requires further study.

PMID- 2001087
TI  - Propafenone treatment of symptomatic paroxysmal supraventricular arrhythmias. A
      randomized, placebo-controlled, crossover trial in patients tolerating oral
      therapy.
AB  - OBJECTIVE: To test the hypothesis that propafenone, administered orally, prevents
      symptomatic paroxysmal supraventricular arrhythmias. DESIGN: a 6-month, open
      label, dose-finding phase followed by a randomized, double-blind, placebo
      controlled, crossover phase, with each treatment period lasting up to 60 days.
      SETTING: An outpatient clinic. PATIENTS: Thirty-three patients with either
      paroxysmal supraventricular tachycardia (n = 16) or paroxysmal atrial
      fibrillation (n = 17) were enrolled. Their arrhythmias were documented by
      electrocardiogram before enrollment. Twenty-three patients (14 with paroxysmal
      supraventricular tachycardia and 9 with paroxysmal atrial fibrillation) were
      randomized and the data obtained from these patients were used in the efficacy
      analysis. INTERVENTION: Propafenone (300 mg three times daily in 19 patients, 300
      mg twice daily in 3 patients, and 150 mg twice daily in 1 patient) and matching
      placebo tablets were administered in a randomized sequence. MEASUREMENTS:
      Symptomatic arrhythmia was documented by telephone transmission of the
      electrocardiogram. MAIN RESULTS: The time to first recurrence was prolonged for
      the overall group of 23 patients while they received propafenone (P = 0.004). The
      recurrence rate of arrhythmia during treatment with propafenone was estimated to
      be approximately one fifth of the recurrence rate during treatment with placebo.
      CONCLUSIONS: Propafenone is effective in reducing symptomatic paroxysmal
      supraventricular arrhythmias.

PMID- 2001088
TI  - A prognostic system for transient ischemia or minor stroke.
AB  - OBJECTIVE: To build a prognostic system for patients with carotid transient
      ischemic attack or minor stroke. DESIGN: Inception cohort study with 2-year
      follow-up. SETTING: Urban community teaching hospital. PATIENTS: Eligible
      patients (n = 142), identified on a carotid ultrasound roster, had been
      hospitalized between 1984 and 1987 within 30 days of a first carotid transient
      ischemic attack or minor stroke. MEASUREMENTS: Stroke or death within 2 years.
      MAIN RESULTS: Three factors were associated with stroke or death: age of more
      than 65 years, diabetes, and hypertension. Based on regression coefficients, age
      of more than 65 years was assigned 3 points; diabetes, 3 points; and
      hypertension, 2 points. An initial prognostic system comprised risk groups 1 (0
      points), 2 (1 to 5 points), and 3 (6 to 8 points). Outcome rates in the three
      groups were 2%, 31%, and 54% (P less than 0.0001), respectively. In an
      independent test sample, the corresponding outcome rates for the initial system
      were 12%, 21%, and 31% (P = 0.04). A final prognostic system, including two
      additional predictors (coronary heart disease [1 point] and the distinction
      between stroke and transient ischemic attack for the baseline event [2 points]),
      comprised risk groups 1 (0 to 2 points), 2 (3 to 6 points), and 3 (7 to 11
      points). Corresponding outcome rates were 3%, 27%, and 48% (P less than 0.001) in
      the original cohort and 10%, 21%, and 59% (P less than 0.001) in the test cohort.
      CONCLUSION: For selected patients with carotid transient ischemia or minor
      stroke, five clinical features can be combined to stratify effectively the risk
      for a subsequent stroke or death.

PMID- 2001089
TI  - Intracardiac shunting across a patent foramen ovale may exacerbate hypoxemia in
      high-altitude pulmonary edema.

PMID- 2001090
TI  - Digoxin for atrial fibrillation: a drug whose time has gone?
AB  - For over 200 years digitalis compounds have been used to treat atrial
      fibrillation. The rapid ventricular response to atrial fibrillation is frequently
      treated with digoxin to produce a controlled heart rate. Digoxin has also been
      proposed as a treatment for terminating recent-onset atrial fibrillation, for
      maintaining sinus rhythm after an episode of atrial fibrillation, and as
      prophylactic therapy in patients with paroxysmal atrial fibrillation to prevent
      excessive tachycardia during a paroxysm. Perhaps because it has been used for so
      long, few of these indications have been studied scientifically until recently.
      Studies now suggest that in patients with atrial fibrillation, digoxin is a poor
      drug for controlling heart rate during exertion, has little or no effect in
      terminating the arrhythmia, and may occasionally aggravate paroxysmal atrial
      fibrillation. Despite adequate digitalization, the heart rate at the onset of a
      paroxysm of fibrillation in patients receiving the drug does not differ from the
      heart rate in patients not receiving it. This article discusses the current role
      of digoxin in the management of patients with chronic, recent-onset, or
      paroxysmal atrial fibrillation.

PMID- 2001091
TI  - Physicians' information needs: analysis of questions posed during clinical
      teaching.
AB  - OBJECTIVE: To describe information requests expressed during clinical teaching.
      SETTING: Residents' work rounds, attending rounds, morning report, and interns'
      clinic in a university-based general medicine service. SUBJECTS: Attending
      physicians, medical house staff, and medical students in a general medicine
      training program. METHODS: An anthropologist observed communication among study
      subjects and recorded in field notes expressions of a need for information. We
      developed a coding scheme for describing information requests and applied the
      coding scheme to the data recorded. Based on assigned codes, we created a subset
      of strictly clinical requests. MEASUREMENTS: Five hundred nineteen information
      requests recorded during 17 hours of observed clinical activity were selected for
      detailed analysis. These requests related to the care of approximately 90
      patients by 24 physicians and medical students. Sixty-five requests were excluded
      because they were not strictly clinical, leaving a subset of 454 clinical
      questions for analysis. MAIN RESULTS: On average, five clinical questions were
      raised for each patient discussed. Three hundred thirty-seven requests (74%)
      concerned patient care. Of these 337 questions, 175 (52%) requested a fact that
      could have been found in a medical record. Seventy-seven (23%) of these
      questions, motivated by the needs of patient care, were potentially answerable by
      a library, a textbook, a journal, or MEDLINE. Eighty-eight (26%) of the questions
      asked for patient care required synthesis of patient information and medical
      knowledge. CONCLUSIONS: Clinicians in the study settings requested information
      frequently. Many of these information needs required the synthesis of patient
      information and medical knowledge and thus were potentially difficult to satisfy.
      A typology is proposed that characterizes information needs as consciously
      recognized, unrecognized, and currently satisfied.

PMID- 2001092
TI  - Infections in HIV-infected travelers: risks and prevention.
AB  - OBJECTIVE: To review risks for infection and to outline strategies to protect the
      health of travelers infected with human immunodeficiency virus (HIV). DATA
      SOURCES: Original reports and summaries of the geographic distribution and
      frequency of infections as well as of special risks these infections impose on
      HIV-infected persons. The recommendations incorporate guidelines published by the
      Centers for Disease Control (CDC) and the World Health Organization. STUDY
      SELECTION: Sources containing the most recent, pertinent information. DATA
      SYNTHESIS: Infections of the gastrointestinal tract are common in all travelers
      to developing countries and are likely to be more frequent, severe, and difficult
      to treat in HIV-infected persons. Prominent among the respiratory tract
      infections that pose special risks to HIV-infected travelers are influenza,
      measles, and fungal infections with geographically focal distributions. The most
      common vector-borne infection, malaria, appears to present relatively little, if
      any, incremental risk to the HIV-infected traveler. Persons with HIV infection
      respond less vigorously to vaccines and have a higher frequency of adverse
      reactions to antimicrobial agents. Nevertheless, immunizations and
      chemoprophylaxis can reduce the risk for many travel-related infections.
      Additionally, there are protective measures that travelers can take to minimize
      exposure to pathogens. CONCLUSIONS: By understanding the risks for disease in
      different destinations, assessing patients' HIV status, counseling patients about
      travel plans and personal protective measures, appropriately using vaccines and
      chemoprophylaxis, as well as instituting early treatment of infection, physicians
      can help HIV-infected patients to preserve their health during travel.

PMID- 2001093
TI  - Distal and proximal colon adenomas.

PMID- 2001094
TI  - "Low-probability" ventilation-perfusion scans.

PMID- 2001095
TI  - Recreational drug use and stroke.

PMID- 2001096
TI  - AIDS and residency training.

PMID- 2001097
TI  - Resource center for occupational and environmental medicine.

PMID- 2001098
TI  - Charles Tomes lecture. Child dental health: 1890-1990.

PMID- 2001099
TI  - Strategic planning for surgery.

PMID- 2001100
TI  - A two-year period of research leading to a degree by thesis is of enormous
      benefit in training a surgeon.

PMID- 2001101
TI  - Asperger's syndrome.

PMID- 2001102
TI  - Possible aetiological factors in childhood leukaemia.

PMID- 2001103
TI  - A new syndrome of congenital hypoparathyroidism, severe growth failure, and
      dysmorphic features.
AB  - Twelve infants (six boys, six girls) with severe hypocalcaemic tetany or
      convulsions were seen over a three year period. Nine patients were symptomatic in
      the newborn period. Their hypocalcaemia was associated with hyperphosphataemia
      and very low concentrations of immunoreactive parathyroid hormone. None of the
      babies suffered from congenital cardiac disease. Cell mediated immunity, measured
      in five patients, was normal. There were no chromosomal abnormalities but all
      patients shared several dysmorphic features including deep set eyes,
      microcephaly, thin lips, beaked nose tip, external ear anomalies, micrognathia,
      and depressed nasal bridge. Mental retardation of varying degree was found in all
      patients. All had severe intrauterine and postnatal growth retardation. Four
      patients have died. The remaining eight patients are on treatments with vitamin D
      and calcium supplements with no change in their growth pattern. We believe that
      this association of congenital hypoparathyroidism with severe growth failure and
      dysmorphism represents a new syndrome.

PMID- 2001105
TI  - Holidays and atopic eczema.
AB  - Information was collected by telephone about 300 holidays taken over a three year
      period by 126 children with severe atopic eczema. During the holidays,
      improvement in eczema occurred more frequently (112/300, 37%) than deterioration
      (63/300, 21%). There was a significant correlation between improvement and a more
      southerly holiday location: improvement was common in holidays taken in the
      Mediterranean or further south (63/92, 69%), but holidays in northern Britain
      were more likely to be associated with deterioration (27/100, 27%) than
      improvement (13/100, 13%). Changes in eczema were correlated with changes in
      asthma in 231 holidays taken by children with both conditions, but improvement
      was not significantly associated with pet ownership. All patients returned to
      their preholiday state, usually within two weeks of return home. The causes of
      changes in eczema while on holiday have not been identified.

PMID- 2001104
TI  - Depot testosterone in boys with anorchia or gonadotrophin deficiency: effect on
      growth rate and adult height.
AB  - Eleven teenage boys with bilateral anorchia and 12 with gonadotrophin deficiency
      were treated by injections of testosterone ester (enanthate) at an initial dose
      of 100 mg every six to eight weeks, rising to 250 mg every four weeks after three
      to four years. In the anorchic boys average adult height was 177.1 cm, compared
      with a mean mid-parental height of 174.4 cm, and mean predicted adult heights of
      177.0 cm (Tanner-Whitehouse method) and 178.0 cm (Bayley-Pinneau method). In the
      patients with gonadotrophin deficiency, mean adult height was 176.9 cm, compared
      with a mean mid-parental height of 176.1 cm, and mean predicted adults heights of
      174.0 cm (Tanner-Whitehouse method) and 177.3 cm (Bayley-Pinneau method). We
      conclude that this testosterone regimen allows achievement of full growth
      potential in such patients.

PMID- 2001106
TI  - Hydration in severe acute asthma.
AB  - Twenty children were studied during severe attacks of acute asthma to find out
      how dehydrated they were on admission to hospital. Mean body weight on admission
      was 97.8% of their reference stable weight seven to 10 days after the attack and
      in only three children was it less than 95% of the stable weight. Bedside
      assessment of dehydration was unreliable. The mean packed cell volume was
      significantly higher on admission than 7-10 days later (0.44 compared with 0.42,
      difference 0.02 SE 0.01). Serum sodium and potassium concentrations and
      osmolality on admission were within normal ranges. The degree of dehydration
      correlated best with a fall in blood pH. There was no association between the
      degree of dehydration and the recovery of the peak expiratory flow rate during
      the first 24 hours or thereafter. We conclude that mild dehydration is common in
      severe acute childhood asthma. Fluid given at a rate of 50 ml/kg/24 hours was
      safe and appropriate for these children.

PMID- 2001107
TI  - Body water measurement in growth disorders: a comparison of bioelectrical
      impedance and skinfold thickness techniques with isotope dilution.
AB  - Total body water was estimated as part of the assessment of body composition in
      children with growth disorders, using the newly commercially available method of
      bioelectrical impedance. This was undertaken to compare the precision and
      accuracy of the results with those derived from skinfold thickness against
      measurement of stable isotopically labelled water (H2(18)O) dilution as a
      standard. The comparisons were carried out to see to what extent the impedance
      method could be applied with confidence to assessment of children with growth
      disorders. Total body water was derived from impedance (I) using an association
      with height (Ht2/I). Impedance and skinfold thickness estimates of total body
      water were equally precise when compared with values obtained from H2(18)O
      dilution (limits of agreement -1.9 to +1.3 and -1.7 to +2.0 kg respectively). The
      mean intraobserver coefficient of variation for repeat measurements of impedance
      was 0.9% compared with 4.6% for skinfold thickness with an interobserver
      coefficient of variation for impedance of 2.8%. Bioelectrical impedance
      estimation of body composition is likely to be of value in the growth clinic when
      expertise in measurement of skinfold thickness is limited or repeated
      measurements are to be undertaken by different observers.

PMID- 2001108
TI  - Raised urinary secretory IgA in chronic diarrhoea.
AB  - Secretory IgA outputs in urine have been measured in 24 malnourished Gambian
      children who had been admitted to hospital with chronic diarrhoea and in 43
      children from a rural Gambian village. Village children of poor nutritional state
      (less than or equal to 74% weight for age compared with the National Center for
      Health Statistics reference curve) had secretory IgA outputs that were only one
      third of those of better nourished individuals. In contrast, the patients with
      chronic diarrhoea had secretory IgA outputs that were significantly raised
      compared with village children, regardless of nutritional state. These results
      demonstrate that secretory IgA production in the urinary tract can be stimulated
      by intestinal disease, suggesting that malnourished children are able to mount a
      response to mucosal infection and supporting the hypothesis of a common secretory
      immune system.

PMID- 2001109
TI  - Handwashing and cohorting in prevention of hospital acquired infections with
      respiratory syncytial virus.
AB  - Hospital acquired infections with respiratory syncytial virus are a major
      problem. The virus is spread predominantly by infected nasal secretions and we
      investigated whether we could reduce its incidence by cohorting babies on each
      ward into designated areas and encouraging staff and parents to wash their hands.
      We examined the incidence of hospital acquired infection due to respiratory
      syncytial virus in all children less than 2 years old and in those with
      congenital heart disease. In 1986-7, before any intervention, 18 (4.2%) of 425
      hospitalised children less than 2 years old developed hospital acquired infection
      due to respiratory syncytial virus. In 1987-8, after intervention, five (0.6%) of
      840 children developed hospital acquired infection but there were fewer ward
      admissions with community acquired infections due to the virus. In 1988-9, when
      there were more community acquired infections than 1986-7, six (1.1%) of 552
      children developed hospital acquired infection. In 1986-7, eight (34.8%) of 23
      children less than 2 years old with congenital heart disease developed hospital
      acquired infection due to respiratory syncytial virus; all eight were among 11
      children with congenital heart disease hospitalised for more than 14 days. In
      1987-8, one (3.3%) of 30 children with congenital heart disease developed
      hospital acquired infection due to respiratory syncytial virus and in 1988-9
      there was one (2.1%) case out of 47 children with congenital heart disease.
      Handwashing and cohorting significantly reduce the incidence of nosocomial
      respiratory syncytial virus infection.

PMID- 2001110
TI  - Association between urinary symptoms at 7 years old and previous urinary tract
      infection.
AB  - The association between current micturition habits and previous urinary tract
      infection was analysed among 3553 school entrants aged 7 years by means of a
      questionnaire. A high incidence of urinary infection, confirmed by urine culture,
      was found (145 (8.4%) in the 1719 girls and 32 (1.7%) in the 1834 boys). There
      was a significant association between current symptoms that were suggestive of
      disturbed bladder function and previous urinary tract infection, but only among
      girls who were over 3 years of age at the time the first episode was diagnosed.

PMID- 2001111
TI  - Social environment and height: England and Scotland 1987 and 1988.
AB  - This study was designed to investigate the social characteristics associated with
      the height of primary schoolchildren aged from 5 to 11. Data were analysed for
      8491 representative sample children measured in England and Scotland in 1987 and
      1988 and 3203 inner city children measured in England in 1987. Height was
      negatively associated with social class but the association was not significant
      after allowing for biological variables. A negative gradient of height with size
      of sibship was evident in white children but was less so in Afro-Caribbean and
      Asian children. The individual associations of 11 different environmental
      characteristics were examined after allowing for biological factors and size of
      sibship. Consistent associations with height included a negative gradient of
      height with increasing latitude and an association of taller stature with
      increasing maternal age. A social class gradient in height is accounted for by
      associations with biological factors, particularly the parental heights;
      environmental attributes are weakly associated with height after allowing for
      biological factors.

PMID- 2001112
TI  - Physical activity patterns defined by continuous heart rate monitoring.
AB  - To investigate the physical activity patterns of British primary schoolchildren
      (mean (SD) 10.7 (0.3) years) the minute by minute heart rates of 67 boys and 65
      girls were monitored continuously for three 12 hour periods during normal
      schooldays. In addition 39 children had their heart rates monitored during a 12
      hour period on a Saturday. Few children experienced the volume (frequency,
      intensity, and duration) of physical activity associated with an improvement in
      cardiopulmonary fitness. Shorter (five minute) periods of the required intensity
      were, however, quite common. No difference between moderate amounts of activity
      was detected between boys and girls, but the boys had more five minute sessions
      of intense activity than the girls. These findings suggest that more research
      into the effects of short periods of intense physical activity on the
      cardiopulmonary systems of young children is required and that the determinants
      of habitual physical activity require further investigation especially in the
      context of sex differences at such an early age.

PMID- 2001113
TI  - Urinary 3-hydroxyproline excretion in Alport's syndrome: a non-invasive screening
      test?
AB  - Alport's syndrome is characterised by morphological and structural changes of the
      renal basement membranes. As the hydroxyproline content of isolated glomerular
      basement membranes is reduced in patients with Alport's syndrome, it is possible
      that the renal excretion of 3-hydroxproline (3-OHP), a key substrate of basement
      membrane collagen, may be altered in such patients. The urinary excretion of 3
      OHP was determined by thin layer chromatography in 20 patients with Alport's
      syndrome, in healthy control subjects, and in patients with other renal diseases.
      These included patients with poststreptococcal glomerulonephritis, lower urinary
      tract infection, severe reflux nephropathy, lithium induced nephropathy,
      polycystic kidney disease, familiar benign haematuria, and renal graft rejection.
      Urinary excretion of 3-OHP was significantly higher in patients with Alport's
      syndrome compared with the patients with other renal diseases and the healthy
      control subjects. All other renal diseases investigated had 3-OHP values within
      the normal range. Urinary 3-OHP determination detected patients with Alport's
      syndrome with a high sensitivity (95.2%) and specificity (97.2%). We therefore
      suggest using urinary 3-OHP determinations as a simple non-invasive screening
      test for Alport's syndrome.

PMID- 2001114
TI  - 45,X/46,X dic (Y) mosaicism in a phenotypic male.
AB  - Cytogenetic analysis, confirmed by in situ hybridisation studies, showed a mosaic
      45,X/46,X dic (Y) (q12) karyotype in a 14 year old boy who was initially
      diagnosed as having Noonan's syndrome. He made an early response to recombinant
      growth hormone; this suggests that this treatment may improve final height.

PMID- 2001115
TI  - Blue breath holding is benign.
AB  - In their recent publication in this journal, Southall et al described typical
      cyanotic breath holding spells, both in otherwise healthy children and in those
      with brainstem lesions and other malformations. Their suggestions regarding
      possible autonomic disturbances may require further study, but they have adduced
      no scientific evidence to contradict the accepted view that in the intact child
      blue breath holding spells are benign. Those families in which an infant suffers
      an 'apparently life threatening event' deserve immense understanding and help,
      and it behoves investigators to exercise extreme care and self criticism in the
      presentation of new knowledge which may bear upon their management and their
      morale.

PMID- 2001116
TI  - Cyanotic 'breath holding' and sudden death.

PMID- 2001117
TI  - Is Asperger's syndrome a useful diagnosis?

PMID- 2001118
TI  - Accidental poisoning in children: can we admit fewer children with safety?

PMID- 2001119
TI  - Establishment of working definitions in nocturnal enuresis.

PMID- 2001120
TI  - Circulatory effects of fast ventilator rates in preterm infants.

PMID- 2001121
TI  - Antiviral and antibacterial lipids in human milk and infant formula.

PMID- 2001122
TI  - Fluorescein dilaurate test of exocrine pancreatic function in cystic fibrosis.

PMID- 2001123
TI  - Effects of overweight on lung function.

PMID- 2001124
TI  - An emotional trigger mechanism for sudden infant death.

PMID- 2001125
TI  - Circulating malignant cells in Burkitt's lymphoma: possible role in tumour
      dissemination.

PMID- 2001126
TI  - Gaming the system. Dodging the rules, ruling the dodgers.
AB  - Although traditional obligations of fidelity require physicians to deliver
      quality care to their patients, including to utilize costly technologies,
      physicians are steadily losing their accustomed control over the necessary
      resources. The "economic agents" who own the medical and monetary resources of
      care now impose a wide array of rules and restrictions in order to contain their
      costs of operation. However, physicians can still control resources indirectly
      through "gaming the system," employing tactics such as "fudging" that exploit
      resource rules' ambiguity and flexibility to bypass the rules while ostensibly
      honoring them. Physicians may be especially inclined to game the system where
      resource rules seriously underserve patients' needs, where economic agents seem
      to be "gaming the patient," with needless obstacles to care, or where others,
      such as hospitals or even physicians themselves, may be denied needed
      reimbursements. Though tempting, gaming is morally and medically hazardous. It
      can harm patients and society, offend honesty, and violate basic principles of
      contractual and distributive justice. It is also, in fact, usually unnecessary in
      securing needed resources for patients. More fundamentally, we must reconsider
      what physicians owe their patients. They owe what is theirs to give: their
      competence, care and loyalty. In light of medicine's changing economics, two new
      duties emerge: economic advising, whereby physicians explicitly discuss the
      economic as well as medical aspects of each treatment option; and economic
      advocacy, whereby physicians intercede actively on their patients' behalf with
      the economic agents who control the resources.

PMID- 2001127
TI  - Causes and consequences of blood pressure alterations in obstructive sleep apnea.
AB  - The obstructive sleep apnea (OSA) syndrome has been considered to be a cause of
      both transient blood pressure elevations during sleep and sustained hypertension
      during the awake state. The purpose of this review was to examine critically the
      existing literature regarding (1) the blood pressure alterations associated with
      OSA, (2) causal mechanisms relating specific blood pressure alterations to OSA,
      and (3) potential consequences of the systemic circulatory abnormalities
      associated with OSA. Particular attention was directed at studies that assessed
      the prevalence of OSA in patients with hypertension and that examined the effects
      on blood pressure of treatment of OSA. We conclude that patients with OSA have
      abnormal sleep blood pressure patterns, manifested most frequently by apnea
      associated blood pressure elevations. Confounding factors such as obesity and
      antihypertensive drug therapy, and conflicting evidence regarding changes in
      daytime blood pressure after therapy for OSA, make it premature to conclude that
      OSA and daytime hypertension are directly associated. Circumstantial evidence
      suggests that the blood pressure alterations that occur during sleep could
      contribute to the high cardiovascular morbidity in patients with OSA. Further
      research into the relationship between OSA and hypertension should improve the
      future care of patients with these conditions and enhance our understanding of
      cardiopulmonary pathophysiology.

PMID- 2001128
TI  - Bad news: delivery, dialogue, and dilemmas.
AB  - The narrative from a real patient encounter is used to illustrate the powerful
      effect that delivering bad news can have on both patient and physician. The
      meaning of bad news to the patient may be quite different than the medical or the
      personal meaning to the physician. Differences in perception must be explored and
      understood before the common ground necessary for joint decision making is
      established. Initial patient responses can be divided into three categories: (1)
      basic psychophysiologic (fight-flight or conservation-withdrawal), (2) cognitive,
      and (3) affective. Responses vary considerably depending on the meaning of the
      diagnosis to the patient, the degree of immediate threat, and the patient's
      previous experience with illness. Desired outcomes of the initial meeting include
      (1) minimizing aloneness and isolation for both patient and physician; (2)
      achieving a common perception of the problem; (3) giving information tailored to
      the immediate needs of the patient; (4) addressing immediate medical needs,
      including the risk of suicide; (5) responding to immediate discomforts; and (6)
      ensuring a basic plan for follow-up. Though all clinicians deliver bad news, few
      have had formal training or open exploration of the profound potential impact of
      the experience.

PMID- 2001129
TI  - Changes in physician practice for the prevention of cardiovascular disease.
AB  - To determine recent changes in physicians' practices for cardiovascular disease
      risk reduction, a randomly selected sample of practicing primary care physicians
      in the upper Midwest was interviewed by telephone in 1987 and again in 1989
      (response rates, greater than 90%; N = 241). The reported mean cutoff levels for
      labeling a total serum cholesterol level as abnormal dropped from 5.84 to 5.43
      mmol/L (226 to 210 mg/dL) and for initiating medication, from 7.34 to 6.54 mmol/L
      (284 to 253 mg/dL). The proportion of physicians using diuretics as preferred
      step 1 antihypertensive agents dropped from 60% to 32%. Preferences became evenly
      divided among diuretics, angiotensin-converting enzyme inhibitors, and beta
      blockers. Advice about physical exercise changed little, but consensus among
      practicing physicians was high. Substantial improvements were found in smoking
      cessation activities. Practicing physicians are proving to be responsive to new
      scientific evidence and education in the prevention of cardiovascular disease.

PMID- 2001130
TI  - The association of allergen skin test reactivity and respiratory disease among
      whites in the US population. Data from the Second National Health and Nutrition
      Examination Survey, 1976 to 1980.
AB  - Data collected on 12- to 74-year-old whites (N = 10,854) during the second
      National Health and Nutrition Examination Survey, 1976 to 1980, a sample of the
      US population, were used to determine the association between various respiratory
      symptoms and the degree of allergen skin test reactivity. Prick-puncture testing
      using eight unstandardized allergens was performed. Allergen skin test reactivity
      was classified by means of the mean diameter of the erythema reaction at the 20
      minute reading. Nonreactors were the comparison group. The prevalence of allergic
      rhinitis increased as allergen skin test reactivity increased, with the odds
      ratio exceeding 8 for the group with two or more positive test results. The
      prevalence of asthma increased with increasing allergen skin test reactivity only
      in nonsmokers. The odds ratio for allergic rhinitis with allergen skin test
      reactivity was higher with outdoor than indoor allergens. The association of
      allergic rhinitis with allergen skin test reactivity was higher when a physician
      had previously diagnosed allergic rhinitis. Chronic rhinitis was not associated
      with allergen skin test reactivity.

PMID- 2001131
TI  - Perceived quality of life and preferences for life-sustaining treatment in older
      adults.
AB  - We investigated whether perceived quality of life is associated with preferences
      for life-sustaining treatment for older adults. Participants included chronically
      ill, elderly outpatients (N = 258) and their primary physicians (N = 105).
      Patients and physicians were independently administered a questionnaire regarding
      patient quality of life and preferences for cardiopulmonary resuscitation and
      mechanical ventilation for the patient. Physicians rated patients' global quality
      of life, physical comfort, mobility, depression, anxiety, and family
      relationships significantly worse than did patients. Nearly all perceptions of
      patients' quality of life were significantly associated with physicians'
      perceptions, but not patients' treatment preferences. Patient-physician agreement
      on patient global quality of life was not significantly associated with agreement
      regarding treatment preferences. We conclude that primary physicians generally
      consider their older outpatients' quality of life to be worse than do the
      patients. Furthermore, physicians' estimations of patient quality of life are
      significantly associated with physicians' attitudes toward life-sustaining
      treatment for the patients. For the patients, however, perceived quality of life
      does not appear to be associated with their preferences for life-sustaining
      treatment.

PMID- 2001132
TI  - Leukopenia, neutropenia, and reduced hemoglobin levels in healthy American
      blacks.
AB  - Hematologic profiles of 462 persons, mostly active-duty service members, were
      studied to determine whether hematologic differences between blacks and whites
      exist in a healthy population. Whites had significantly greater mean
      concentrations of leukocytes (6.73 vs 5.95 x 10(9)/L), neutrophils (3.96 vs 3.16
      x 10(9)/L), and hemoglobin (153 vs 135 g/L for men, 147 vs 125 g/L for women).
      The mean differences were largely due to relatively symmetric shifts in the
      frequency distributions for these cell concentrations. No significant correlation
      was found between neutrophil count and morbidity from infection as measured by a
      standardized questionnaire. The use of separate hematologic reference values for
      blacks and whites should be considered.

PMID- 2001133
TI  - Effect of marked peripheral leukocytosis on the leukocyte count in ascites.
AB  - Patients with high peripheral leukocyte counts are sometimes found to have high
      leukocyte counts in ascitic fluid in the presence of negative cultures. To
      determine if peripheral leukocytosis (greater than or equal to 20 x 10(9)/L) by
      itself can result in high leukocyte or neutrophil counts in ascites, 29 patients
      were studied. A total of 31 paracenteses were performed in these patients as soon
      as the high peripheral leukocyte count was determined. Culture of ascitic fluid
      was performed using blood-culture bottles. The mean peripheral leukocyte count
      was 29.3 +/- 9.3 x 10(9)/L, with a mean neutrophil count of 19.9 +/- 6.5 x
      10(9)/L. The mean ascitic fluid neutrophil count was 0.064 +/- 0.054 x 10(9)/L
      (range, 0.007 to 0.197 x 10(9)/L). No significant correlation was found between
      peripheral neutrophil (or leukocyte) count and neutrophil (or leukocyte) count in
      ascitic fluid. Marked peripheral leukocytosis (or neutrophilia) does not seem to
      have an effect on the leukocyte or neutrophil count in ascitic fluid.

PMID- 2001134
TI  - Characteristics of patients with syphilis attending Baltimore STD clinics.
      Multiple high-risk subgroups and interactions with human immunodeficiency virus
      infection.
AB  - Medical records of 341 patients with syphilis seen at a health department
      sexually transmitted disease clinic were reviewed to assess membership in high
      risk subgroups and interactions with human immunodeficiency virus (HIV)
      infection. When compared with the entire clinic population, patients with
      syphilis tended to be older and were more likely to acknowledge intravenous drug
      use, more often had a history of syphilis, and, among men, were more often
      homosexually active. Half of the men with syphilis and one third of the women
      fell into one or more of these high-risk subgroups. Patients with syphilis were
      also more likely to test positive for HIV infection than other patients attending
      the clinic. Patients admitting to intravenous drug use, prior syphilis, or being
      homosexually active were significantly more likely to be HIV seropositive than
      patients without these characteristics, even though patients with these
      characteristics were significantly more likely to refuse HIV serologic testing.
      Although clinical stage of syphilis at presentation did not differ when patients
      with and without concurrent HIV infection were compared, geometric mean rapid
      plasma reagin titers were significantly higher in HIV-infected patients with
      secondary syphilis.

PMID- 2001135
TI  - Human immunodeficiency virus infection and indeterminate western blot patterns.
      Prospective studies in a low prevalence population.
AB  - Interpretation of human immunodeficiency virus (HIV) antibody results that are
      "indeterminate" rather than clearly positive or negative is problematic for the
      person delivering the result as well as for the individual being tested. To
      improve counseling messages for these individuals, we evaluated data collected
      from a well-characterized cohort of 387 blood donors who had been monitored for
      up to 2 years. We sought to determine if persons with indeterminate Western blot
      patterns were infected with HIV, and whether information derived from follow-up
      monitoring would assist in the development of counseling messages for persons on
      whom no follow-up information was available. Donors were studied by laboratory
      assays, clinical evaluation, and assessment of risk for HIV. The absence of HIV
      infection in 97 of 98 donors with indeterminate Western blot patterns was
      confirmed by clinical follow-up, Western blot assays of sequential samples, and
      negative gene amplification results. We propose supplemental guidelines to be
      used as an adjunct to existing interpretive criteria for counseling individuals
      when they first present with an indeterminate Western blot finding.

PMID- 2001136
TI  - Eosinophilia-myalgia syndrome. A clinical case series of 21 patients. New Mexico
      Eosinophilia-Myalgia Syndrome Study Group.
AB  - We reviewed 21 cases of eosinophilia-myalgia syndrome to describe the range of
      clinical findings in these patients. Most patients were women (20 [95%]) and
      middle-aged (mean, 46 years) and had taken the food supplement L-tryptophan
      (95%). All cases involved eosinophilia (eosinophil count, greater than or equal
      to 2.0 x 10(9)/L) and incapacitating myalgias. Fourteen (88%) of the 16 patients
      tested had mild liver function abnormalities. Aldolase levels were abnormal in
      all patients tested. Muscle biopsies were done in five patients; four showed
      eosinophilic perimyositis, and one had interstitial inflammation. No physical
      finding was pathognomonic or universal, but muscle tenderness, tachycardia, and
      rash were the most common signs found during physical examinations. Seven
      patients were treated with prednisone, and six showed improvement in muscle pain
      and a decrease in eosinophilia. The cause of this disorder is still unknown.

PMID- 2001137
TI  - Sharing of information by students in an objective structured clinical
      examination.
AB  - Increasing numbers of medical schools are using Objective Structured Clinical
      Examinations (OSCEs) to evaluate students. An Objective Structured Clinical
      Examination employs a multiple-station format and standardized patients to
      document students' clinical skills. A lengthy format is necessary; testing an
      entire class often necessitates multiple repetitions of the same examination.
      This dictates a need to minimize sharing of information among students. We
      studied six administrations of an Objective Structured Clinical Examination
      designed to measure skills. Analyses were conducted to detect changes in scores
      over the administrations as well as over the 8.5 hours of each day of testing. An
      increase in either might indicate information sharing had occurred. No
      significant increase occurred. If information was shared, it had no significant
      effect on scores. Skills a student uses to approach a patient should not change
      even if the patient's complaints are known.

PMID- 2001138
TI  - Physicians' effectiveness in assessing risk for human immunodeficiency virus
      infection.
AB  - An American Medical Association committee recently recommended that physicians
      routinely screen patients for behaviors that put patients at risk for human
      immunodeficiency virus infection, yet there is evidence that this screening does
      not occur routinely. Faculty, fellows, and residents at a teaching hospital in a
      midwestern state with a low prevalence of acquired immunodeficiency syndrome were
      surveyed regarding their experience in screening for human immunodeficiency
      virus, their training related to substance abuse and human sexuality, and their
      confidence and ease in addressing such topics with their patients. Results
      indicated that only 11% routinely screened patients for high-risk behaviors.
      While most physicians had received training in human sexuality, most had not
      received training in substance abuse screening. Those trained felt more confident
      in addressing substance abuse and human sexuality and felt more comfortable in
      caring for patients known to be infected with human immunodeficiency virus. A
      concerted effort to encourage human immunodeficiency virus risk assessment by
      physicians is needed. This should include training opportunities in screening and
      counseling patients about sexual activities and substance abuse.

PMID- 2001139
TI  - Discussing life-sustaining treatment. A teaching program for residents.
AB  - Ideally, physicians and patients should discuss patient preferences for life
      sustaining treatment before the onset of cognitive impairment or a life
      threatening illness; however, these conversations often do not occur. We
      developed an educational program in which residents practiced discussing advance
      directives with volunteer simulated outpatients and then received feedback from
      the patient, an observing resident, and a faculty member. Residents found the
      training sessions to be realistic, relevant, and useful. Resident self-ratings
      improved significantly on eight items representing knowledge, skills, and
      attitudes about discussing advance directives with patients. Resident learning
      occurred in four major areas: technical knowledge about advance directives;
      introducing the topic to patients; giving patients information; and eliciting
      patients' values and feelings. We conclude that residents need and want training
      in this area and that simulated patients act as a catalyst for their learning.

PMID- 2001140
TI  - Successful treatment of acquired immunodeficiency syndrome-related Mycobacterium
      avium complex disease with a multiple drug regimen including amikacin.
AB  - Disease due to Mycobacterium avium complex (MAC) in patients with the acquired
      immunodeficiency syndrome (AIDS) typically occurs late in the course of AIDS and
      is usually disseminated with evidence of multiorgan involvement. Most patients
      are persistently bacteremic. Previously published studies have noted a poor
      response to antimycobacterial chemotherapy. We describe successful treatment of
      MAC disease in an AIDS patient with a multiple drug regimen, including amikacin,
      clofazimine, rifampin, ethambutol, and ciprofloxacin. This patient, whose
      presentation and MAC disease course distinctly differ from most published
      experience, remains clinically and microbiologically MAC-disease free 25 months
      after initiation of therapy. We describe four additional AIDS patients with MAC
      disease who had a favorable clinical and microbiological response to this regimen
      without developing serious adverse effects after periods ranging from 4 to 12
      months. We suggest a prospective, controlled clinical trial using this regimen
      for treatment of MAC disease in patients with AIDS may be warranted.

PMID- 2001141
TI  - Refractory hypoglycemia secondary to topical salicylate intoxication.
AB  - We describe a case of severe refractory hypoglycemia secondary to topical
      salicylate intoxication. A 72-year-old man with psoriasis and end-stage renal
      disease was treated with a topical cream containing 10% salicylic acid. The
      patient presented with encephalopathy and subsequently developed hypoglycemia
      refractory to infusions of large amounts of glucose. A serum salicylate
      concentration was elevated at 3.2 mmol/L. Emergent hemodialysis was accompanied
      by rapid lowering of serum salicylate concentration and resolution of refractory
      hypoglycemia. Salicylate is well absorbed across normal and diseased skin.
      Salicylate markedly impairs gluconeogenesis and increases glucose utilization,
      resulting in hypoglycemia. To our knowledge, this is the first article on
      hypoglycemia due to the application of topical salicylate.

PMID- 2001142
TI  - Central nervous system magnesium deficiency.
AB  - The central nervous system concentration of magnesium (Mg++) appears to have a
      critical level below which neurologic dysfunction occurs. Observations presented
      suggest that the interchange of the Mg++ ion between the cerebrospinal fluid,
      extracellular fluid, and bone is more rapid and dynamic than is usually believed.
      This is especially so when the hypertrophied parathyroid gland is associated with
      significant skeletal depletion of Mg++ as judged by history rather than serum
      level. Magnesium, much like calcium, has a large presence in bone and has a
      negative feedback relationship with the parathyroid gland. A decline in central
      nervous system Mg++ may occur when the skeletal buffer system orchestrated
      largely by the parathyroid glands is activated by an increase in serum calcium.
      Observations in veterinary medicine and obstetrics suggest that the transfer of
      Mg++ from the extracellular fluid into bone during mineralization processes may
      be extensive. If the inhibition of the hypertrophied parathyroid gland is
      prolonged and the skeletal depletion of Mg++ extreme, serious neurologic
      symptoms, including seizures, coma, and death, may occur. Noise, excitement, and
      bodily contact appear to precipitate neurologic symptoms in Mg+(+)-deficient
      human subjects as it has been documented to occur in Mg+(+)-deficient
      experimental animals. The similarity of the acute central nervous system
      demyelinating syndromes with reactive central nervous system Mg++ deficiency is
      reviewed.

PMID- 2001143
TI  - Flavimonas oryzihabitans (Pseudomonas oryzihabitans; CDC group Ve-2) bacteremia
      in the immunocompromised host.
AB  - Flavimonas oryzihabitans, known previously as Pseudomonas oryzihabitans, and a
      member of the Centers for Disease Control group Ve-2, is a gram-negative organism
      that has rarely been implicated as a human pathogen. Flavimonas oryzihabitans
      appears to be a soil and saprophytic organism that survives in moist environments
      and is indigenous to rice paddles. To our knowledge, only seven cases of human
      infection caused by this organism have been reported; they involved four patients
      with bacteremia and three patients with peritonitis who were receiving continuous
      ambulatory peritoneal dialysis. In this report, we describe three
      immunocompromised patients with catheter-associated bacteremia: a patient with
      cancer, a patient with acquired immunodeficiency syndrome, and a patient with
      sickle cell disease. There is emerging clinical evidence that F oryzihabitans
      should be recognized as an organism that is capable of causing human disease,
      particularly in immunocompromised patients and with the increased usage of
      permanent catheters.

PMID- 2001144
TI  - Melioidosis. Forgotten, but not gone!
AB  - Melioidosis, infection by the soil bacterium Pseudomonas pseudomallei, has the
      potential for prolonged latency with recrudescence into an acute, often
      fulminating, and fatal infection. Although the organism is never found in North
      America, infection is endemic in areas of southeast Asia, and populations of
      service personnel exposed during the Vietnam war and southeast Asian immigrants
      are at risk of severe recrudescent disease. Diagnosis, however, has been missed
      or delayed because of lack of familiarity with this disease. We present a case of
      recrudescent melioidosis that illustrates the difficulties encountered in
      diagnosis and treatment. This case involves a 76-year-old Vietnam veteran who
      presented with melioidosis of the bone 18 years after exposure to the organism
      and 10 years after a missed diagnosis of latent pulmonary disease. This case
      illustrates the protean nature of latent infection and the difficulty of
      selecting successful antibiotic therapy.

PMID- 2001145
TI  - Skepticism about loss of skepticism!

PMID- 2001146
TI  - Tell your kidneys to take a powder.

PMID- 2001147
TI  - Predicting abdominal aortic aneurysm.

PMID- 2001148
TI  - No serum albumin in myeloma.

PMID- 2001149
TI  - Drug interaction with quinolone antibiotics in intensive care unit patients.

PMID- 2001150
TI  - Oral typhoid vaccination for travelers.

PMID- 2001151
TI  - Acute renal failure after an overdose of ciprofloxacin.

PMID- 2001152
TI  - Effusion cytology in the diagnosis of malignant epithelioid and biphasic pleural
      mesothelioma.

PMID- 2001153
TI  - Combined sarcoidosis and disseminated visceral giant cell angiitis: a third
      opinion.

PMID- 2001154
TI  - Transient stress lymphocytosis during crisis of sickle cell anemia.

PMID- 2001155
TI  - Myogenous phenotype of epithelial-like areas in endometrial stromal sarcomas.
AB  - Approximately 25% of low-grade endometrial stromal sarcomas of the uterus contain
      areas of epithelial-like differentiation, which are often reminiscent of ovarian
      sex-cord tumors. It has been suggested that these areas may represent attempted
      differentiation toward either uterine glands or smooth muscle. To investigate
      these two possibilities, we examined the histologic and immunohistochemical
      features of 26 low-grade endometrial stromal sarcomas. Eight tumors had
      epithelial-like differentiation, which in some tumors was so prominent as to
      suggest a purely epithelial neoplasm. Areas typical of endometrial stromal
      sarcoma were vimentin positive, whereas epithelial-like differentiation expressed
      vimentin and the muscle markers muscle-specific actin and desmin, as well as
      cytokeratin, but not the epithelial marker epithelial membrane antigen.
      Epithelial-like differentiation in low-grade endometrial stromal sarcoma is not
      uncommon and, based on our immunohistochemical results after comparison with
      normal controls, epithelial-like differentiation has a myogenous rather than an
      epithelial phenotype.

PMID- 2001156
TI  - Immune complexes in the choroid plexus in liver cirrhosis.
AB  - A histopathologic and immunofluorescence study of the choroid plexus was
      performed in 12 cases of liver cirrhosis (cirrhosis group) and in 20 patients who
      died of diseases with no evidence of liver or brain involvement, and in which
      renal disease and alcoholism were also excluded (control group). IgA, IgG, IgM,
      C3, and C1q were investigated by direct immunofluorescence technique. Positive
      immunofluorescence in the choroid plexus was found in 83.33% of the cirrhosis
      group. IgA and IgG were the immunoglobulins more frequently found. C3 was also
      commonly found. Histologic examination of the choroid plexus showed changes in
      66.67% of the cirrhosis group characterized, mainly, by subepithelial deposition
      of a homogeneous, acidophilic, and periodic acid-Schiff-positive substance, with
      thickening of the epithelial basement membrane. In the control group, the
      immunofluorescence in the choroid plexus was negative in all cases and only two
      cases (10%) presented histopathologic changes of the choroid plexus with a
      pattern similar to that of the cirrhosis group.

PMID- 2001157
TI  - Extramedullary hematopoiesis in the liver in sudden infant death syndrome.
AB  - Liver extramedullary hematopoiesis was examined in 54 victims of sudden infant
      death syndrome and in 21 infants who died of other causes in an attempt to
      confirm Naeye's findings of increased extramedullary hematopoiesis in cases of
      sudden infant death syndrome. Our data showed greater extramedullary
      hematopoiesis in victims of sudden infant death syndrome (F = 23.52), supporting
      Naeye's hypothesis that victims of sudden infant death syndrome have suffered a
      subtle, chronic hypoxemic condition before death.

PMID- 2001158
TI  - Tumefactive fibroinflammatory lesion of the extremity. Report of a case and
      review of the literature.
AB  - Tumefactive fibroinflammatory lesion is an idiopathic fibroinflammatory process
      of the head and neck region. Although benign histopathologically, it is invasive,
      destructive, and locally recurrent, leading to uncertainty regarding its proper
      management; as the disease is rare, determining optimal treatment is difficult,
      given the anecdotal nature of reports. We report the first case of a tumefactive
      fibroinflammatory lesion occurring outside the head and neck region. Our patient
      was treated with corticosteroids and had a favorable response, supporting this
      approach as initial treatment. Immunohistochemical studies performed on a
      pretreatment specimen were consistent with a secondary inflammatory component
      because no monoclonal nor aberrant phenotypes were detected. The tumefactive
      fibroinflammatory lesion appears to be indistinguishable from the other known
      idiopathic fibroinflammatory processes; patients presenting with any one of these
      should be evaluated for the others.

PMID- 2001159
TI  - The ectopic ovary. A case report and review of the literature.
AB  - We describe an ectopic ovary in a stillborn female. To our knowledge, this is the
      first report of an extra ovary in an infant. This case prompted a review of
      ectopic ovarian tissue, which is known by a variety of terms, the most common
      being accessory ovary and supernumerary ovary. We suggest that (1) many of the
      past cases should be classified as ovarian implants rather than true
      embryologically derived ectopic tissue; and (2) the terms accessory ovary and
      supernumerary ovary are imprecise and should be modified.

PMID- 2001160
TI  - Primary rhabdomyosarcoma of the ileum in an adult.
AB  - We report a case of primary rhabdomyosarcoma of the ileum occurring in a 45-year
      old man. The rhabdomyoblastic nature was immunohistochemically confirmed by
      positivity with anti-myoglobin and anti-striated actin antisera. We discuss the
      differential diagnosis with similar tumors. To our knowledge, ileal
      rhabdomyosarcomas have not been previously reported in adults.

PMID- 2001161
TI  - Heterotopic supradiaphragmatic liver formation in association with congenital
      cardiac anomalies.
AB  - Heterotopic supradiaphragmatic liver formation is extremely rare. We studied a
      case of heterotopic liver in a 26-week fetus with severe cardiac and conotruncal
      anomalies. The cardiac anomalies are strikingly similar to those of a previously
      described patient with heterotopic supradiaphragmatic liver. The cardiac
      anomalies and heterotopic supradiaphragmatic liver formation may be
      mechanistically related.

PMID- 2001162
TI  - Papillary endothelial hyperplasia in the thyroid following fine-needle
      aspiration.
AB  - A 74-year-old woman was found to have exuberant papillary endothelial hyperplasia
      within her thyroid gland subsequent to multiple fine-needle aspiration biopsies
      of a Hurthle cell neoplasm. To our knowledge, this histologic alteration in the
      thyroid has not been previously reported. We describe this unusual complication
      following fine-needle aspiration, and we delineate the clinicopathologic and
      differential diagnostic features.

PMID- 2001163
TI  - Hemangiopericytoma of the sternum.
AB  - Hemangiopericytoma of the chest wall is a rare tumor. We describe a patient with
      malignant hemangiopericytoma of the sternum who was treated with primary surgical
      resection and discuss the clinical, radiographic, and histologic features of the
      case. Surgical resection is the primary mode of therapy. High-dose radiotherapy
      and chemotherapy with a doxorubicin hydrochloride-containing combination may be
      warranted in certain cases.

PMID- 2001164
TI  - The role of the United Network for Organ Sharing and designated organ procurement
      organizations in organ retrieval for transplantation.
AB  - With the increasing success of organ transplantation in this country, there are
      increasing numbers of patients who are awaiting a transplantable organ. Congress
      has established a national Organ Procurement and Transplant Network, which is
      administered by the United Network for Organ Sharing. Organ retrieval is
      performed by 70 organ procurement organizations, each having a designated service
      area. The need for transplantable organs falls further and further behind the
      increasing demand.

PMID- 2001165
TI  - Histocompatibility testing in transplantation.
AB  - The question of whether or not HLA is important in transplantation can now be
      answered with a definite yes. The nationwide six-antigen-matching program, in
      which over 100 US transplantation centers have participated, has shown that a
      high (88% to 90%) 1-year graft survival rate can be achieved when kidneys are
      shipped to well-matched recipients. Long-term outcome (measured as half-life) is
      also markedly improved, from an average of 7 years for cadaveric donor
      transplants to as much as 19 years in the six-antigen-matched recipients. One of
      the major factors influencing long-term survival is histocompatibility matching,
      as shown by the survival differences among HLA-identical siblings (25-year half
      life), one-haplotype-mismatched parental donors (12-year half-life), and two
      haplotype-mismatched cadaveric donors (7-year half-life). For the past 25 years
      of kidney transplant experience, cadaveric donor half-life has remained stable at
      7 years, despite many improvements in immunosuppression protocols.
      Histocompatibility matching unquestionably offers the best approach to prevention
      of chronic rejection.

PMID- 2001166
TI  - The role of crossmatching in organ transplantation.
AB  - The preoperative crossmatch is one of the most important laboratory tests in
      organ transplantation. Quality assurance of this laboratory test depends on a
      number of factors that include the serum samples and methodology utilized.
      Clinical correlation with laboratory studies and postoperative outcome of the
      graft and the recipient are essential to understanding this developing field.

PMID- 2001167
TI  - The pathology of heart allograft rejection.
AB  - The pathologist plays an important role in the care of cardiac transplant
      recipients. Day-to-day management of immunosuppression is largely dependent on
      the diagnosis and grading of acute rejection. While noninvasive methods have been
      tried experimentally, the endomyocardial biopsy remains the gold standard in
      monitoring the rejection status of the heart allograft. The diagnosis of
      rejection, however, is complicated by a variety of other histologic findings,
      which may be procedural or processing related, due to sampling, or specifically
      related to transplantation. Failed allografts, whether from autopsy or
      explantation, provide the opportunity to study short- and long-term changes in
      the transplanted heart. Allograft arteriopathy, or graft atherosclerosis, is the
      major limiting factor in long-term recipient survival. While the morphological
      features of graft arteriopathy have been well described, the mechanism and
      factors contributing to its development remain unclear.

PMID- 2001168
TI  - The surgical pathologist's role in liver transplantation.
AB  - Liver transplantation has become an option in treating a wide variety of
      diseases. The surgical pathologist, as a member of the transplantation team, is
      increasingly involved in the evaluation of allograft dysfunction. Interpretation
      of the liver allograft biopsy specimen requires integration of clinical history,
      biochemical data, and histologic patterns of a wide variety of lesions, including
      harvesting injury, vascular thrombosis, rejection, infection, and recurrent
      disease. This article reviews the varied histologic appearances of the more
      common forms of liver allograft injury, the contexts in which they arise, and
      their distinction from one another.

PMID- 2001169
TI  - Immunology of renal allograft rejection.
AB  - Allograft rejection remains the critical problem of renal transplantation. The
      immunologic mechanisms that underlie renal allograft rejection are heterogeneous
      and involve the humoral and cellular limbs of the immune response. Antibody
      mediated hyperacute rejection is now rare owing to improved prospective cross
      matching. Chronic rejection, characterized by intrarenal arterial fibrosis, is
      still poorly understood. Knowledge of the afferent and efferent processes
      involved in rejection has led to effective therapeutic and experimental
      strategies that employ monoclonal antibodies and other pharmacologic agents to
      reverse, or prevent, acute allograft rejection. In addition, allospecific
      tolerance has been achieved experimentally and clinically in a variety of
      manners. Preliminary studies on the mechanism of allograft tolerance induced by
      donor-specific blood transfusions before transplantation suggest a role for an
      immunoregulatory cell population that specifically down regulates cytotoxic
      lymphocyte responses to donor antigens in some recipients. A role for
      noninherited maternal antigens and anti-idiotypic antibodies in down regulating
      immune responses to allografts have also been reported by several studies. An
      improved understanding of allograft rejection and tolerance may identify
      approaches to prolong allograft survival without the morbidity and mortality
      associated with present-day immunosuppression.

PMID- 2001170
TI  - The role of the immunogenetics laboratory in marrow transplantation.
AB  - Allogeneic marrow transplants from genotypically HLA-identical siblings have
      become lifesaving therapy for patients with various congenital and acquired
      diseases of the immune and hematopoietic systems. Unfortunately, less than 30% of
      patients in the United States have an HLA-identical sibling; therefore, many are
      denied the opportunity for potentially curative treatment for otherwise fatal
      conditions. The results of marrow transplantation from haploidentical family
      members who were partially compatible for nonshared haplotypes with the patients
      demonstrated the relevance of HLA compatibility for engraftment and graft-vs-host
      disease. These results have provided the rationale for using HLA-identical
      unrelated volunteers as marrow donors. The recent development of a national
      registry of volunteer bone marrow donors (the National Marrow Donor Program in
      the United States) has made it possible to access a centralized file of more than
      260,000 HLA-typed volunteers. Marrow transplants from an unrelated donor have
      become feasible. However, our preliminary clinical experience clearly
      demonstrated an increase in the incidence and severity of graft-vs-host disease.
      It is likely that standard HLA typing techniques are not adequate to provide data
      for sufficient donor and recipient matching. It is possible that currently
      available molecular technology could be applied to HLA typing and donor matching
      to improve on clinical results.

PMID- 2001171
TI  - The role of the laboratory in marrow manipulation.
AB  - A variety of manipulations are performed on marrow for transplantation.
      Allogeneic transplantation may require red blood cell or plasma removal if the
      transplant is ABO incompatible, or T-cell depletion if there is a high risk of
      graft-vs-host disease. Autologous marrow must be preserved, either in the liquid
      or frozen state. If there is a chance of neoplastic cell involvement, these cells
      need to be killed or removed. Initial processing generally involves production of
      a buffy coat. Automated means using blood cell processors are available. Further
      purification of the desired progenitor cells may include discontinuous density
      gradient centrifugation. Depletion techniques can be physical (eg, elutriation or
      sheep red blood cell rosette removal) or chemical (eg, treatment with 4
      hydroperoxycyclophosphamide). Monoclonal antibodies can be used covalently bound
      to toxin molecules, attached to magnetic beads, or with an exogenous source of
      complement. Antibodies to the CD34 human hematopoietic marker allow positive
      selection of desired progenitor cells. Quality control of marrow processing
      involves measurement of various hematologic parameters, careful process
      monitoring, bacterial/fungal and hematopoietic progenitor cultures,
      quantification of residual contaminating cells, and observation of clinical
      effect. Alternate sources of progenitors for transplant include peripheral blood,
      cord blood, fetal liver, and cadavers.

PMID- 2001172
TI  - The role of the clinical microbiology laboratory in transplantation.
AB  - The clinical microbiology laboratory plays a central role in any transplantation
      program. Pretransplantation microbiologic testing often determines prophylactic
      treatment, donor selection, and blood product use. With suspected infection,
      rapid microbiologic tests permit prompt therapy but are challenged by an ever
      changing diversity of potential pathogens and limited specimen size. Antigen
      detection and the polymerase chain reaction with nucleic acid hybridization are
      newer methods that promise earlier detection of such serious infections as
      disseminated aspergillosis and primary cytomegalovirus and may reveal new
      microbial causes of various posttransplantation syndromes.

PMID- 2001173
TI  - Current status of organ preservation with University of Wisconsin solution.
AB  - A retrospective analysis of all organs that were preserved with University of
      Wisconsin solution was undertaken to assess the impact of this solution on early
      allograft function. From May 1987 until June 1990, 181 livers, 92 pancreata, and
      92 kidneys were preserved with University of Wisconsin solution for extended
      periods of time. The mean (+/- SD) preservation times were as follows: liver,
      12.6 +/- 4.5 hours; pancreas, 16.7 +/- 4.4 hours; and kidney, 18.3 +/- 4.3 hours.
      The overall rate of primary nonfunction and hepatic artery thrombosis were 6.1%
      and 3.9%, respectively. No differences in the rates of primary nonfunction and
      hepatic artery thrombosis were noted for combined liver-pancreas procurement vs
      isolated liver retrievals or when reduced-size liver transplants were compared
      with nonreduced liver transplants. Likewise, no difference in primary nonfunction
      or hepatic artery thrombosis was seen in livers that were preserved for less than
      6, 6 to 12, and greater than 12 hours. However, serum aminotransferase levels and
      prothrombin times were lower on the first postoperative day in livers that were
      preserved for less than 6 hours when compared with 6 to 12 or greater than 12
      hours. Early pancreatic allograft function was also excellent for up to 24 hours
      of cold-storage preservation. All patients were immediately insulin independent,
      and there were no cases of initial nonfunction or graft pancreatitis. There were
      only two cases (2.2%) of pancreatic vascular thrombosis in this series. No
      difference in pancreatic function was noted for organs that were preserved for
      less than 6, 6 to 12, or greater than 12 hours. Likewise, renal allograft
      function was excellent, with only two patients (2.2%) requiring postoperative
      hemodialysis. The actuarial 1-month patient survival for liver and pancreas
      kidney transplant recipients was 91.5% and 98.9%, respectively. Actuarial 1-month
      allograft survival for liver, pancreas, and kidney transplants was 83.0%, 96.7%,
      and 97.8%, respectively. In conclusion, University of Wisconsin solution
      represents a significant advancement in cold-storage organ preservation and is
      ideally suited as a universal intra-abdominal aortic-flush and cold-storage
      solution.

PMID- 2001174
TI  - The plus strand is discontinuous in a subpopulation of unintegrated HIV-1 DNA.
AB  - During reverse transcription the synthesis of plus strand viral DNA is initiated
      from an RNA polypurine primer immediately upstream of the U 3 region. The
      polypurine tract (PPT) sequence at this site is in HIV-1 also present in the
      middle of the genome. Here we demonstrate that a subpopulation of linear
      unintegrated HIV-1 DNA has a discontinuity in the plus strand within less than 50
      bp from this central PPT, consistent with its utilization as a plus strand
      initiation site.

PMID- 2001175
TI  - Production of infectious particles from defective human immunodeficiency virus
      type 1 (HIV-1)-producing cell clones by superinfection with infectious HIV-1.
AB  - A total of 81 cell clones persistently infected with the LAV-1 or HTLV-IIIB
      strain of human immunodeficiency virus type 1 (HIV-1) was isolated from cells
      which were obtained by serial passage of some proliferating MT-4 cells after a
      drastic cytolysis of most cells by HIV-1-infection. These cell clones were
      classified into 8 types (I to VIII) in terms of the expression of HIV-1 antigens,
      syncytium formation capacity, and reverse transcriptase activity and infectivity
      of virus particles in the culture fluid. Type I cell clones were producers of
      infectious HIV-1 particles, while types II to VIII cell clones did not produce
      infectious HIV-1 or were producers of uninfectious defective HIV-1 particles.
      Immunoprecipitation followed by SDS-polyacrylamide gel electrophoresis (PAGE)
      showed that the gag precursor protein in L-2 cell clone (type IV) was not cleaved
      to mature gag proteins, while the env precursor protein on L-3 cell clone (type
      III) was not cleaved to mature env protein. H-7 cell clone (type VIII) did not
      express any HIV-1 antigen. All these cell clones after the superinfection with
      infectious HIV-1 synthesized intact gag and env proteins, which were, at least in
      part, related to the HIV-1 genome persistently present in the cell clones before
      the superinfection, resulting in production of infectious HIV-1. For example, it
      was found that L-2 cell clone contained a single copy of the LAV-1 genome per
      haploid cell and produced doughnut-shaped particles. On the other hand, the cell
      clone isolated from the L-2 cell clone superinfected with infectious HTLV-IIIB
      contained the integrated HTLV-IIIB genome in addition to the LAV-1 genome present
      before the superinfection, and produced intact HIV-1 particles in addition to
      doughnut-shaped particles from a single cell. These results indicate that
      complementation and/or genetic recombination events in the superinfected cells
      may account for the production of infectious intact HIV-1 virions.

PMID- 2001176
TI  - Nucleotide sequence of the 3' terminal region of lettuce mosaic potyvirus RNA
      shows a Gln/Val dipeptide at the cleavage site between the polymerase and the
      coat protein.
AB  - DNA complementary to the 3' terminal 1651 nucleotides of the genome of the common
      strain of lettuce mosaic virus (LMV-O) has been cloned and sequenced.
      Microsequencing of the N-terminus enabled localization of the coat protein gene
      in this sequence. It showed also that the LMV coat protein coding region is at
      the 3' end of the genome, and that the coat protein is processed from a larger
      protein by cleavage at an unusual Q/V dipeptide between the polymerase and the
      coat protein. This is the first report of such a site for cleavage of a potyvirus
      polyprotein, where only Q/A, Q/S, and Q/G cleavage sites have been reported. The
      LMV coat protein gene encodes a 278 amino acid polypeptide with a calculated Mr
      of 31,171 and is flanked by a region which has a high degree of homology with the
      putative polymerase and a 3' untranslated region of 211 nucleotides in length.
      Percentage of homology with the coat protein of other potyviruses confirms that
      LMV is a distinct member of this group. Moreover, amino acid homologies noticed
      with the coat protein of potexvirus, bymovirus, and carlavirus elongated plant
      viruses suggest a functional significance for the conserved domains.

PMID- 2001177
TI  - Three antibody molecules can bind simultaneously to each monomer of the tetramer
      of influenza virus neuraminidase and the trimer of influenza virus hemagglutinin.
AB  - Trimeric hemagglutinin and tetrameric neuraminidase molecules isolated from
      influenza virus bind an average of 9 and 13 molecules respectively of monovalent
      antibody fragments prepared from IgG isolated from polyclonal sera. In each case
      this represents an average of approximately three molecules of antibody binding
      to each protomer. Although there is compelling evidence for the presence of
      multiple adjacent and overlapping epitopes covering the surface of these two
      viral antigens, steric hindrance ensures that even under saturating conditions
      only three molecules of monovalent antibody fragments can be simultaneously
      accommodated on each monomer.

PMID- 2001179
TI  - Further warnings from Australia concerning intraspinal steroids.

PMID- 2001178
TI  - Immunological and virological characterization of improved construction of
      recombinant vaccinia virus expressing rinderpest virus hemagglutinin.
AB  - We constructed a recombinant vaccinia virus (RVV) expressing rinderpest virus
      (RPV) hemagglutinin (H) by modifying the promoter region of the original RVV. The
      promotor region was modified at three points, i.e., an outframe ATG was
      eliminated, the sequence between the promoter and initiation codon was shortened
      and the base sequence just upstream of the initiation codon was changed. As
      compared with the original RVV, the modified RVV was found to produce a
      remarkably large amount of H protein in infected rabbit kidney cells cultured in
      vitro and to induce high titers of anti-RPV-H antibodies in rabbits. The median
      protective doses in rabbits of the modified and of the original RVVs were 10(2)
      pfu and 10(3.5) pfu, respectively, indicating that the modified RVV was at least
      10-times more effective in protection than the original. The neurovirulence of
      the modified RVV and the parental LC16mO strain was roughly at the same level,
      and was much lower than that of WR strain. The modified RVV was as heat-stable as
      the original one. These results indicate that the modified RVV could be a
      candidate rinderpest vaccine for further examinations including cattle.

PMID- 2001180
TI  - Comments on brain tissue transplantation without immunosuppression.

PMID- 2001181
TI  - Familial progressive vestibulocochlear dysfunction.

PMID- 2001182
TI  - Quantitative neurologic and neurobehavioral testing of persons infected with
      human immunodeficiency virus type 1.
AB  - Assessment of neurobehavioral and peripheral neurologic performance among
      homosexual men was made on two occasions, using a computer-administered
      neurobehavioral instrument and quantitative vibration threshold testing,
      respectively. Persons studied included high-risk human immunodeficiency virus
      (HIV)-negative men (n = 13), asymptomatic HIV-positive men (n = 30), and patients
      with acquired immunodeficiency syndrome (AIDS)-related complex of AIDS (n = 17).
      In addition, subjects were characterized immunologically at the time of
      neurologic and neuropsychologic assessment via determination of circulating
      lymphocyte counts (total lymphocytes, helper T cells, suppressor T cells, total T
      cells, activated T cells) and markers of HIV type 1 (HIV-1) infection. At the
      first cycle of testing, the results of asymptomatic HIV-positive men were
      indistinguishable from those of HIV-negative men, while persons with AIDS-related
      complex or AIDS tended to have lower mean performance. These differences did not
      achieve statistical significance on any single test, but the group with AIDS
      related complex or AIDS had the worst mean performance on 12 of 13 individual
      performance tests. Thirty-seven men underwent repeated testing after a mean
      interval of approximately 4.5 months. There was little change in mean
      neurobehavioral performance and vibratory thresholds among all three groups.
      Measures of neurobehavioral performance and vibrotactile thresholds were not
      correlated with measures of immunological status. These results are consistent
      with the concept that asymptomatic infection with HIV-1 does not imply the
      presence of measurable or significant neurologic or neurobehavioral impairment.

PMID- 2001183
TI  - Risk of dementia in first-degree relatives of patients with Alzheimer's disease
      and related disorders.
AB  - First-degree relatives of patients with Alzheimer's disease (AD) are at greater
      risk for dementia when compared with the relatives of their healthy peers, but
      not when compared with the relatives of patients with Parkinson's disease. This
      may indicate that the risk of dementia in these relatives is not specific to AD
      or that these studies are biased. We obtained a family history and vital status
      information on each first-degree relative of patients attending a clinic and in a
      group of recruited healthy elderly subjects. Patients formed two groups: probable
      AD and other forms of dementia or cognitive disorders without dementia. The odds
      of dementia in first-degree relatives did not differ between patient groups. The
      odds of dementia in relatives of patients with probable AD or other forms of
      dementia was six times that in the relatives of the healthy elderly subjects. The
      cumulative incidence of dementia increased with age in the first-degree relatives
      of all subjects. Approximately 50% of the first-degree relatives of patients with
      AD were demented by age 91 years, but almost the same number of the other patient
      group's relatives were demented as well. That figure was never reached in the
      healthy elderly subject's relatives. Because the risk of dementia in first-degree
      relatives of patients with AD was similar to that for patients with other
      disorders, we cannot exclude the possibility that this is the result of selection
      and information biases. Our investigation implies that the increased risk of
      dementia may not be specific to relatives of patients with AD; the risk may also
      be increased in first-degree relatives of patients with other neurologic
      disorders.

PMID- 2001184
TI  - Assessing the severity of dementia. Patient and caregiver.
AB  - In dementia there is cognitive impairment, disability in daily life, and
      sometimes behavioral disturbance. These changes are a burden for the caregivers
      of patients with dementia. Few studies are available that examine all these
      aspects and their interrelationships in a single patient group. In our study we
      selected detailed methods for assessment of all these aspects. Interrelationships
      were studied in 30 mild to moderately impaired patients with dementia and their
      caregivers. Although the relations of cognitive deterioration to disability in
      daily life and of burden experienced by the caregiver to patient's condition were
      stronger than often reported, it was impossible to deduce the overall severity of
      dementia from one single aspect. Thus, for effective management of patients and
      caregivers, for evaluation of individual treatment or of clinical trials,
      attention should be paid to all the different aspects of patients' condition and
      caregivers' burden. Outcome measurements will then be more valid.

PMID- 2001185
TI  - Detection of abnormal memory decline in mild cases of Alzheimer's disease using
      CERAD neuropsychological measures.
AB  - The present study was designed to determine which of the memory tasks included in
      the CERAD (Consortium to Establish a Registry for Alzheimer's Disease)
      neuropsychological battery best differentiate patients with early Alzheimer's
      disease from cognitively normal elderly control subjects and also best
      distinguish between the various levels of severity of the dementia process. A
      sample of CERAD patients with Alzheimer's disease was stratified by disease
      severity into those with mild, moderate, or severe dementia and matched with
      control subjects for sex, age, and education. Using multivariate procedures and
      cutting scores, the efficacy of each memory measure in distinguishing between
      these groups and control subjects was determined. The test for delayed recall was
      found to be the best overall discriminatory measure. The other tests of memory,
      ie, immediate recall, intrusion errors, and recognition memory, had poor overall
      discriminability. None of the CERAD memory measures were found to be particularly
      powerful in staging the severity of dementia. These findings suggest that tests
      for delayed recall may be particularly useful in the early detection of
      Alzheimer's disease and should be considered in screening batteries for dementia
      in community surveys.

PMID- 2001186
TI  - Antecedent medical diseases in patients with amyotrophic lateral sclerosis. A
      population-based case-controlled study in Rochester, Minn, 1925 through 1987.
AB  - Odds ratios (ORs) were estimated for the prevalence of antecedent endocrine,
      metabolic, or vascular diseases among 45 patients with amyotrophic lateral
      sclerosis from the Rochester, Minn, population compared with 90 control subjects
      matched for sex, year of birth, period of observation, and residence.
      Hypertension occurred less frequently in male patients with amyotrophic lateral
      sclerosis (4%) than in control subjects (30%; OR = .10). Because of small
      population size, no conclusions can be drawn with respect to the following
      antecedent conditions: thyroid disease (OR = 1.61), coronary artery disease (OR =
      .58), obesity (OR = .52), diabetes (OR = 1.00), cerebrovascular disease (OR =
      .21), and peripheral vascular disease (OR = 1.23). The heterogeneity of
      antecedent thyroid disease makes it highly unlikely that any specific thyroid
      lesion is causally associated with most cases of amyotrophic lateral sclerosis.
      Hypertension may be a marker for protective factors against the development of
      amyotrophic lateral sclerosis in men.

PMID- 2001187
TI  - Environmental risk factors in siblings with Parkinson's disease.
AB  - To investigate possible risk factors in Parkinson's disease, we conducted a case
      controlled study of 19 families having two or more siblings with Parkinson's
      disease. Demographic data were collected, including lifetime histories of places
      of residence; sources of drinking water; occupations, such as farming; and
      exposure to herbicides and pesticides. Rural living and drinking well water, but
      not farming and herbicide exposure, were significantly increased in 38
      parkinsonians compared with 38 normal control subjects. A comparison of
      parkinsonian siblings with siblings with essential tremor revealed no differences
      in any risk factors for the years of shared environment. These data suggest that
      living in a rural environment and drinking well water are risk factors for
      Parkinson's disease and that the total life exposure to an environmental toxin
      may be more important than exposure in early life.

PMID- 2001188
TI  - An assessment of disability rating scales used in multiple sclerosis.
AB  - Twenty patients with clinically definite, stable multiple sclerosis were examined
      independently by three of us at the same visit and given scores on the Ambulation
      Index, Expanded Disability Status Scale, and Kurtzke Functional System scales.
      Observer error accounted for 12% to 55% of the variation observed between
      individual Kurtzke Functional System scores, 17.1% of the variation observed
      between the patients' Expanded Disability Status Scale scores, and only 3.9% of
      the variation between Ambulation Index scores. The implications of these findings
      for the choice of scales in clinical trials are described.

PMID- 2001189
TI  - Heterogeneity in spasmodic dysphonia. Neurologic and voice findings.
AB  - Spasmodic dysphonia is a disturbance of phonation with laryngeal spasms. We
      report voice and neurologic examination findings in 45 subjects. Neurologic
      abnormalities were found in 32 subjects (71.1%). Rapid alternating movement
      abnormalities, weakness, and tremor were common. Incoordination and spasticity
      were rare. Lower extremity findings were frequent. Abnormalities were bilateral.
      Spasmodic dysphonia severity was related to age. Type, severity, and duration of
      vocal symptoms were not different for subjects with or without neurologic
      abnormalities. Vocal tremor was more frequent in neurologically abnormal
      subjects. Involvement of a pallidothalamic-supplementary motor area system could
      account for neurologic findings, brain imaging findings, and clinical
      heterogeneity. The view emerging is that spasmodic dysphonia is a manifestation
      of disordered motor control involving systems of neurons rather than single
      anatomical sites.

PMID- 2001191
TI  - Arthur Conan Doyle, Joseph Bell, and Sherlock Holmes. A neurologic connection.
AB  - Neurologists, like physicians in several other medical specialties, can lay claim
      to Sherlock Holmes as one of their own. This assertion is validated by the number
      of neurologic conditions, such as seizures, stroke, syncope, encephalopathies,
      and head trauma, that are mentioned in the stories and novels. In addition, the
      article reviews the powers of observation and the deductive approach utilized by
      Conan Doyle and Joseph Bell, the models for Sherlock Holmes, and how these skills
      can be applied to medical problems.

PMID- 2001190
TI  - Lateral deviation of the eyes on forced lid closure in patients with cerebral
      lesions.
AB  - We examined 35 patients with unilateral cerebral lesions to determine the
      incidence of lateral deviation of the eyes under forcefully closed lids and the
      reliability of this sign in predicting the side of the lesion. Only patients with
      radiologically confirmed unilateral lesions were studied. Over 70% of patients
      had contralateral ocular deviation (Cogan's "spasticity of conjugate gaze"), 20%
      had ipsilateral deviation, and less than 9% of the patients had no deviation.
      Lateral ocular deviation was as sensitive, but not as specific, as a unilateral
      Babinski plantar response in determining the side with the lesion. Contralateral
      deviation was more common with parietotemporal localization, suggesting that the
      phenomenon reflects an underlying disturbance of attentional mechanisms.

PMID- 2001192
TI  - Lymphomatous polyneuropathy. Biopsy of clinically involved nerve and successful
      treatment.
AB  - We present a patient with large-cell lymphoma in remission who, over several
      weeks, developed widespread multifocal polyneuropathy. There was involvement of
      all four limbs, most severely the left upper extremity that had become useless.
      Biopsy of the left saphenous nerve within an area of sensory loss showed lymphoma
      in the endoneurium. There was no other evidence of recurrent lymphoma despite
      extensive investigation, including bone marrow, lumbar puncture, magnetic
      resonance imaging of the spine, and computed tomography of the abdomen and
      pelvis. Intensive systemic chemotherapy was accompanied by nearly complete
      recovery. Biopsy of a symptomatic nerve is preferable to routine sural nerve
      biopsy in this condition because of its patchy distribution. Treatment with
      systematic chemotherapy can be effective.

PMID- 2001193
TI  - Horner's syndrome from hypothalamic infarction.
AB  - We report a case of Horner's syndrome due to ipsilateral posterior hypothalamic
      infarction, occurring in the absence of other signs of hypothalamic dysfunction.
      Associated symptoms of contralateral faciobrachial weakness and dysarthria
      correlated with the extension of the infarct into the posterior limb of the
      internal capsule seen by magnetic resonance imaging. The likely vascular anatomy
      of this lesion is discussed.

PMID- 2001194
TI  - Complex abdominal aortic reconstruction.

PMID- 2001195
TI  - Low-cost teleradiology for Australia.
AB  - Teleradiology refers to the transmission of clinical images from their source to
      remote sites. In this paper a low-cost means of establishing teleradiology using
      conventional personal computers is described. This is a simple and effective
      means of transmitting valuable clinical data from hospital to hospital, and
      hospital to individual, markedly enhancing the quality of clinical communication.
      The system described herein has proved invaluable in a busy neurosurgical
      department, in both emergency and more routine settings. Teleradiology has the
      potential to transform the early management of critically ill and injured
      patients, especially those from remote parts of Australia.

PMID- 2001196
TI  - Concomitant renal artery revascularization and aortic reconstruction in the adult
      patient.
AB  - Concomitant renal artery revascularization and aortic reconstruction in the adult
      patient are thought to be associated with a high degree of morbidity and
      mortality. This has been attributed to the diffuse nature of atherosclerosis
      generally present in these patients and, as a consequence, a poor overall medical
      condition. Although this series confirms the fragile pre-operative nature of
      these patients it demonstrates that, with careful surgical management, they can
      be treated effectively.

PMID- 2001197
TI  - Warm blood cardioplegia as an adjunct to myocardial preservation during coronary
      artery bypass grafting.
AB  - A review of the first 52 consecutive coronary artery bypass surgery patients to
      receive oxygenated blood cardioplegia, with warm reperfusion cardioplegia ('hot
      shot'), was undertaken to evaluate its effectiveness in myocardial protection.
      The chosen parameters of ischaemia were: (i) the occurrence of ventricular
      fibrillation (VF) on release of the aortic cross-clamp (ACC); (ii) the occurrence
      of bradycardia due to cardiac conduction defects; (iii) the use of inotropes with
      or without the use of the intra-aortic balloon pump (IABP); (iv) evidence of
      myocardial infarction (MI) on the postoperative electrocardiograph (ECG); and (v)
      peri-operative cardiogenic mortality. Warm induction cardioplegia was cooled
      after cardiac standstill. Repeat cold cardioplegia was given as required at
      intervals and warm reperfusion cardioplegia was given prior to release of the
      ACC. Of the 52 patients studied none developed VF after release of the ACC; one
      patient with pre-operative complete heart block required temporary cardiac
      pacing; no patient required inotropes or IABP and there was no postoperative MI
      or mortality. The warm blood cardioplegia technique has not resulted in any
      detectable evidence of inadequate myocardial protection. A beneficial effect has
      been demonstrated by the absence of VF, cardiac conduction defects, myocardial
      failure, MI and mortality.

PMID- 2001198
TI  - Clinicopathological features of primary gastrointestinal lymphomas: a study of 42
      cases.
AB  - The clinicopathological features of 42 patients with gastrointestinal lymphoma
      during the period 1982-88 are described. Ten cases (23.8%) were seen in the
      stomach, 23 cases (54.8%) in the small intestine and 9 cases (21.4%) in the large
      intestine. In 4 cases multiple sites were involved. The tumours occurred most
      frequently in the 2nd to 4th decade. Histologically, using the working
      formulation for non-Hodgkin's lymphoma, all were found to be diffuse and mostly
      of the high grade type (45%). Seven lymphomas were seen in children. Three were
      of the Burkitt's type. Patients presented quite late in a large number of cases
      (43%). Compared with most other published series small intestinal involvement was
      common. There was a high incidence in males. Predominant small intestinal
      involvement did not result in malabsorption syndrome and primary lymphomas
      constituted 3.5% of all malignancies of the gastrointestinal tract.

PMID- 2001199
TI  - Presentation, duration of symptoms and staging of colorectal carcinoma.
AB  - A prospectively recorded, consecutive series of 155 colorectal carcinoma
      specimens clinically and pathologically staged according to the Australian
      Clinico-pathological System (ACPS) between April 1987 and May 1989 at Wellington
      and Kenepuru Hospitals is reviewed. Clinical records were available for
      retrospective review for 146 of the 155 patients. Change in bowel habit, rectal
      bleeding and abdominal pain were the most common presenting symptoms. Thirty-five
      patients presented as emergencies, twenty-six with obstruction and nine with
      perforation. Abdominal pain resulted in the earliest surgical intervention. The
      median duration of symptoms prior to diagnosis was 3 months. No correlation
      existed between tumour stage and duration of symptoms. Earlier diagnosis during
      the symptomatic phase of colorectal carcinoma is unlikely to contribute
      significantly to improved overall survival.

PMID- 2001200
TI  - Voyaging to New Zealand: the medical challenge.

PMID- 2001201
TI  - Superior mesenteric artery aneurysms: a case report.
AB  - Aneurysms of the superior mesenteric artery (SMA) are rare, accounting for 8% of
      visceral artery aneurysms. Aneurysms at the site are very liable to rupture,
      irrespective of size, and may be difficult to manage even in the elective
      situation. The fact that 50-60% of SMA aneurysms are mycotic has important
      implications in the selection of the appropriate surgical procedure. In this
      paper we report a case of an SMA aneurysm diagnosed at the time of impending
      rupture and treated successfully. The aetiology, mode of presentation, diagnosis
      and management of SMA aneurysms are discussed.

PMID- 2001202
TI  - False aneurysm of cervical carotid artery from intraplaque haemorrhage: a case
      report.
AB  - A case of non-traumatic extracranial carotid false aneurysm in a patient with
      carotid atherosclerotic occlusive disease and a recent history of a cerebral
      ischaemic event but without any history of carotid artery surgery or cervical
      trauma, is reported.

PMID- 2001203
TI  - Bleeding cystic artery aneurysm: rare cause of haemobilia.
AB  - A case of a bleeding cystic artery aneurysm which presented with recurrent
      episodes of haemobilia is presented. The diagnosis was established at emergency
      visceral angiography and cholecystectomy was curative.

PMID- 2001204
TI  - Teleradiology.

PMID- 2001205
TI  - Basingstoke replies.

PMID- 2001206
TI  - Surgeons, gallstones and the gall-bladder.

PMID- 2001207
TI  - Cardiac output by impedance cardiography: two alternative methodologies compared
      with thermodilution.
AB  - One critical component of the Kubicek (8) stroke volume equation, used to measure
      cardiac output by impedance cardiography, is dZ/dt(max). The present study,
      conducted on six anesthetized dogs, compared impedance cardiac output derived
      using two alternative methods of quantifying dZ/dt(max), with simultaneous
      thermodilution measures. Values for dZ/dt(max) quantified relative to dZ/dt = 0
      baseline and relative to the dZ/dt B-point were entered into the Kubicek equation
      to generate cardiac output measures designated as impedance-A and impedance-B,
      respectively. Emphasis was placed upon evaluating impedance cardiac output within
      its accepted limits as a relative change measure. Systematic alterations in
      cardiac output were produced by intravenously administered isoproterenol,
      phenylephrine and nitroprusside. Drug-induced changes in cardiac output measured
      by the impedance-A method were statistically identical to thermodilution. For the
      impedance-B method, similarity to thermodilution was limited to two of the three
      drug conditions. Correlations of impedance cardiac output with thermodilution
      tended to be higher for the impedance-A method. Together with theoretical and
      practical considerations, these results support quantification of dZ/dt(max)
      relative to dZ/dt = 0 when used in the Kubicek stroke volume equation.

PMID- 2001208
TI  - Unpredictability of fighter pilot G tolerance using anthropometric and
      physiologic variables.
AB  - Correlation and regression analyses were used to study relationships between
      centrifuge G tolerances of 1,434 fighter pilots during High-G Training (HGT) and
      anthropometric and physiologic variables. Multiple regression analyses yielded a
      four-variable model in which gradual onset run (GOR) relaxed-G tolerance was
      inversely correlated with height and directly correlated with age, weight, and
      diastolic blood pressure. Although the four-variable model was able to predict
      more of the variation in G tolerance than any single variable, neither method
      showed a correlation (r) of greater than 0.35 with GOR relaxed or straining G
      tolerance. No subject variable was significantly different between the pilot
      groups that did and did not experience G-induced loss of consciousness. We
      conclude that prediction of G tolerance during centrifuge HGT is unreliable using
      anthropometric and physiologic variables. The anti-G straining maneuver remains
      the major determinant of an individual's G tolerance.

PMID- 2001209
TI  - Locomotion and motion sickness during horizontally and vertically reversed
      vision.
AB  - Locomotion and motion sickness during reversed vision were studied in ten normal
      subjects and a patient with bilateral labyrinthine loss. Whereas horizontal
      reversal produced moderate to severe gait disturbances as well as motion sickness
      in all normal subjects, vertical reversal failed to induce such symptoms. The
      patient, being free of motion sickness during both reversals, could not walk
      straight during horizontal reversal. The difference in the strength of sensory
      mismatch between both directions seemed to result from a difference in the role
      of vision for spatial orientation which is produced by the proprioceptive as well
      as otolithic inputs of gravity.

PMID- 2001210
TI  - Motion sickness severity under interaction of vection and head movements.
AB  - Vection alone, or combined with head movements, has been shown to invoke motion
      sickness (MS). This study's purpose was to observe how different combinations of
      vection and head movements influenced the severity of MS. We tested 26 subjects
      in a rotating sphere at a speed of 45 degrees/s, resulting in vertical yaw,
      horizontal roll or pitch vection. Coincidently, subjects pitched, rolled, or
      yawed their heads (0.5 Hz, 20 degrees). We found that yaw vection combined with
      pitch or roll head movements significantly increased MS, while pitch vection with
      any type of head movement, or head and scene rotation about the same axis
      significantly reduced MS. When the head was kept stationary, pitch vection was
      most stressful for MS, followed by roll vection, then yaw vection, although yaw
      vection was the strongest sensation of self-rotation.

PMID- 2001211
TI  - The interaction of hand vibration with oculomanual coordination in pursuit
      tracking.
AB  - The effects of high frequency hand vibration (150 Hz) on simultaneous ocular and
      manual tracking performances were investigated in trained human subjects. First,
      a zero-order pursuit tracking task was performed with and without direct visual
      control of the hand. Second, eye tracking of an imaginary target linked to the
      hand was also performed. The results show that hand vibration significantly
      alters eye and hand tracking performances when the hand is out of sight. However,
      when the hand is placed in the visual field, tracking performances are less
      affected by vibration. Visual cues on limb segments may compensate to some extent
      for the vibration-induced alteration of proprioceptive information otherwise used
      to control movements. Eye movements are altered during vibration while the
      subject is tracking or fixating an imaginary target attached to the hand. These
      findings explicitly show that hand vibration can perturb oculo-manual
      coordination control. The present results imply that vibration-induced activity
      of somesthetic mechanoreceptors is likely to contribute to oculomanual
      coordination alteration and tracking decrement in vibratory environments.
      Furthermore, direct visual control of the hand and/or arm may be of particular
      interest in manipulation tasks executed under vibration.

PMID- 2001212
TI  - Coping behaviors of U.S. Army flight nurses in World War II: an oral history.
AB  - War is a universally stressful event that may tax or exceed one's ability to
      cope. This study addressed how flight nurses with the U.S. Army Air Forces in
      World War II coped with war; the purpose was to analyze data obtained from oral
      histories of 25 flight nurses who served in World War II. Content analysis of the
      data revealed two levels of coping; a taxonomy of coping efforts was developed
      for each level. The microscopic level consisted of specific external and internal
      demands occurring during the war that necessitated coping. The macroscopic level
      consisted of behavioral and cognitive efforts used to cope with the war in
      general. Findings suggest that the women perceived their wartime experience as a
      challenge rather than as a threat and were thus able to make the best of the
      stressful wartime situation.

PMID- 2001213
TI  - Aircrew decision-making behavior in hazardous weather avoidance.
AB  - In-flight encounters with hazardous weather represent one of the most significant
      safety issues in civil aviation operations. Aircrew judgment is often cited as
      the probable cause of incidents and accidents involving weather, although lack of
      information is also a factor. The present study examines how information,
      presented at different times and in different forms, affects the awareness and
      decision-making behavior of aircrews in a flight simulation study of a recent
      microburst/windshear incident. In order to examine the influence of enhanced
      information transfer on aircrew behavior, intracrew communications and approach
      to-land decisions were evaluated with conventional ATC communications and with
      automated cockpit alerting and display of weather information. Results of the
      study revealed that aircrews provided only with conventional ATC transmissions of
      weather information had difficulty discriminating conditions conducive to
      microburst events from less hazardous windshear events. Improved situation
      awareness for microburst events was found when ground-based convective weather
      information was provided in real time to aircrews. Avoidance decision-making was
      found to be less efficient with conventional ATC alert transmissions when
      compared to the performance of crews provided with a visual display of microburst
      events. The importance of information transfer on aircrew situation awareness and
      decision-making in hazardous weather avoidance is discussed.

PMID- 2001214
TI  - Primary flight training performance of student naval aviators with vision
      waivers.
AB  - Performance was studied for student naval aviators with waivers for defective
      uncorrected distance visual acuity who underwent primary flight training at NAS
      Whiting Field, FL, for fiscal year 1987 (cases = 45). Outcome variables were
      completion rate, primary flight training grades and flight hours. Controls for
      completion rate were all other students during that period (N = 1443). For
      training grades and hours, controls were selected who completed the same training
      squadron within 1 month of the case. Two controls were selected who progressed to
      the jet pipeline, with two additional controls selected who progressed to the
      same pipeline as the cases, either maritime/patrol or helicopter (controls =
      180). Results demonstrated the cases were significantly more likely to complete
      training (p = 0.029), but not significantly different in primary flight grades or
      hours. These results suggest student naval aviators on vision waivers were
      competitive with their contemporaries.

PMID- 2001215
TI  - Post-exercise time-course analysis of ST segment and T wave changes: an important
      contribution to the role of stress electrocardiography in aircrew.
AB  - Flight surgeons recognize that ongoing vigilance is necessary to detect coronary
      artery disease (CAD) in aircrew. Regular physical examinations with only a
      resting electrocardiogram, albeit having a very low predictive value for
      detection of CAD in asymptomatic subjects, are now widely practised. Routine
      stress electrocardiography has been criticized for yielding too many so-called
      "false positive" results because ST/T changes that develop during and after
      exercise are prevalent. Recent studies in our institution indicate, however, that
      the time-course behavior patterns of these ST/T configurational "abnormalities"
      after exercise are different from those reflecting myocardial ischemia due to
      epicardial CAD. Time-course analysis increases the predictive value of exercise
      testing and has dramatically decreased the number of asymptomatic aircrew being
      subjected to coronary arteriography in our institution. Routine exercise
      electrocardiography provides a reliable, cost-effective means of detecting
      aircrew with CAD and a baseline for comparison at subsequent examination, and we
      strongly recommend that it be universally reinstated.

PMID- 2001216
TI  - A statistical note on the redundancy of nine standard baroreflex parameters.
AB  - An accepted method for measuring the responsiveness of the carotid-cardiac
      baroreflex to arterial pressure changes is to artificially stimulate the
      baroreceptors in the neck with a pressurized neck chamber. Nine physiological
      responses to this type of stimulation are quantified and used as indicators of
      the baroreflex response function. Thirty male humans between the ages of 27 and
      46 underwent the carotid-cardiac baroreflex test. The data for the nine response
      parameters were analyzed by principle component factor analysis. The results
      indicated that 92.5% of the total variance across all nine parameters could be
      explained in four dimensions. The first two dimensions reflected location points
      for R-R interval and carotid distending pressure, respectively. The third factor
      was composed of measures reflecting the gain (responsiveness) of the reflex. The
      fourth dimension was the ratio of baseline R-R interval to the maximal R-R
      interval response during simulated hypertension. The data suggest that the
      analysis of all nine baroreflex parameters is likely to be redundant and
      researchers should account for these redundancies either in their analyses or
      conclusions.

PMID- 2001217
TI  - A latex mask for collection of expired gases from goats.
AB  - A latex respiratory mask was developed to collect expired gas from goats in
      studies of ventilatory adaptation to high altitude. The snouts of 15 animals were
      dimensioned by taking girth measurements. The procedure requires a rough positive
      mold of wood which is repeatedly submerged into latex, then slowly rotated upon
      removal until skim-like layers form a mask. A supporting harness is attached to
      the mask by use of three flat straps connected by Dot fasteners. A period of
      several hours per day for up to 2 weeks may be necessary to allow the animal to
      become accustomed to wearing the mask.

PMID- 2001218
TI  - Wings for a flier's spouse.
AB  - This paper discusses how the wings insignias can be used to understand the
      pilot's environment. The author uses as an example the French Navy Wings, and
      emphasizes the role of spouses in helping pilots to cope with stress.

PMID- 2001219
TI  - Cases from the aerospace medicine residents' teaching file. Case #41. A student
      pilot presents with asymptomatic hypercalcemia during his initial class I
      physical.

PMID- 2001220
TI  - A spade or sanguinary excavating implement (SEI).

PMID- 2001221
TI  - Lower back pain, decreased libido, occasional dysuria and urgency when sitting in
      the "jet".

PMID- 2001222
TI  - A 38 year old military pilot referred with complaints of profound malaise, fever,
      rigors, myalgia, intermittent headaches and nausea of 2 days duration.

PMID- 2001223
TI  - Changes in body fluid compartments during a 28-day bed rest.
AB  - The extravascular fluid responses to real or simulated space-flight are not well
      documented. In this study serial isotope measurements were used to obtain
      measurements of the body fluid responses of 10 22-29-year-old men during 28 d of
      simulated microgravity (bed rest). The subjects were maintained on a controlled
      metabolic diet for 7 d before the study, during 14 d of ambulatory control, 28 d
      of horizontal bed rest, and 14 d of ambulant recovery. Fluid compartments were
      measured on control days 1 and 9, bed rest days 2, 14, and 28, and recovery days
      7 and 14. By day 2 of bed rest, plasma volume (PV) and extra-cellular volume
      (ECV) decreased significantly by an average 209 and 533 ml, respectively. Red
      cell volume (RCV) and total body water (TBW) decreased more slowly, with average
      losses of 128 and 1,316 ml, respectively, after 28 d of bed rest. Early in the
      bed rest, TBW loss was mostly from the ECV. Thereafter, the TBW deficit was
      derived from the intracellular compartment, which decreased an average of 838 ml
      after 28 d. These results suggest losses from all fluid compartments during bed
      rest, with no evidence of restoration of ECV after 1-2 weeks.

PMID- 2001224
TI  - Glucagon and ammonia influence the long-term regulation of phosphate-dependent
      glutaminase activity in primary cultures of rat hepatocytes.
AB  - 1. Glutaminase activity was measured in primary cultures of hepatocytes. 2.
      Enzyme activity decreased markedly after 24-40 h in culture, and this loss of
      activity was accompanied by loss of enzyme protein. 3. The loss of activity was
      delayed by high concentrations of glutamine, and was abolished by the continuous
      presence of NH4Cl in the culture medium. 4. In cells from rats fed on high
      carbohydrate protein-free diet, glutaminase activity was increased by glucagon,
      but not by dexamethasone. This induction was observed only in the continuous
      presence of NH3 or high concentrations of glutamine. 5. It is concluded that NH3
      and glutamine are essential for the stabilization and induction of glutaminase
      activity in hepatocytes. The inactivation of glutaminase in hepatocytes and in
      vivo under certain conditions may be due to lack of NH3 in the extracellular
      medium.

PMID- 2001225
TI  - Factors influencing the inactivation of phosphate-dependent glutaminase in the
      matrix fraction of rat liver mitochondria.
AB  - 1. The activity of phosphate-dependent glutaminase was measured in a matrix
      extract of essentially lysosome-free liver mitochondria. 2. ATP, GTP or a non
      hydrolysable analogue of ATP stimulated the rapid inactivation of glutaminase,
      but not of other matrix enzymes. 3. Glutaminase was protected against
      inactivation if high concentrations of glutamine or low concentrations of NH3
      were present. 4. Inactivation of glutaminase in the presence of ATP did not
      markedly affect the reaction of the enzyme with a specific polyclonal antiserum.
      5. These results in a mitochondrial extract are similar to the characteristics of
      glutaminase inactivation in intact hepatocytes, suggesting a similar mechanism in
      each case. 6. The presence of a specific ATP-activated protease in the
      mitochondrial matrix is suggested to be responsible for glutaminase inactivation.

PMID- 2001226
TI  - Surfactant protein composition of lamellar bodies isolated from rat lung.
AB  - Lamellar bodies isolated from rat lung contain all three classes of surfactant
      proteins, SP-A, SP-B and SP-C, as determined by immunoblot analysis. The amounts
      of the surfactant proteins present in lamellar bodies, determined by sandwich
      e.l.i.s.a. (SP-A) and fluorescamine assay (SP-B and SP-C) show that these
      organelles are highly enriched in the hydrophobic surfactant proteins SP-B and SP
      C.

PMID- 2001227
TI  - Modification of host cell membrane lipid composition by the intra-erythrocytic
      human malaria parasite Plasmodium falciparum.
AB  - The phospholipid and fatty acid compositions of the host infected erythrocyte
      plasma membrane (IEPM) have been determined for erythrocytes infected with the
      human malaria parasite Plasmodium falciparum. IEPM were prepared by selective
      lysis of the host erythrocyte (but not of the parasite membranes) with 0.1%
      saponin, followed by differential centrifugation. The purity of the IEPM was
      determined by measuring the membrane-specific enzyme markers
      acetylcholinesterase, glutamate dehydrogenase and lactate dehydrogenase, and by
      immunoelectron microscopy using monoclonal antibodies specific for human
      erythrocyte glycophorin A (4E7) and for a 195 kDa parasite membrane glycoprotein
      (Pf6 3B10.1). Both approaches demonstrated that the host erythrocyte plasma
      membrane preparation was free from contamination by parasite membranes. During
      intra-erythrocytic development of the parasite, the phospholipid composition of
      the erythrocyte membrane was strikingly altered. IEPM contained more
      phosphatidylcholine (38.7% versus 31.7%) and phosphatidylinositol (2.1% versus
      0.8%) and less sphingomyelin (14.6% versus 28.0%) than normal uninfected
      erythrocytes. Similar alterations in phospholipid composition were determined for
      erythrocyte membranes of parasitized cells isolated by an alternative method
      utilizing polycationic polyacrylamide microbeads (Affigel 731). The total fatty
      acid compositions of the major phospholipids in IEPM were determined by g.l.c.
      The percentage of polyunsaturated fatty acids in normal erythrocyte phospholipids
      (39.4%) was much higher than in phospholipids from purified parasites (23.3%) or
      IEPM (24.0%). The unsaturation index of phospholipids in IEPM was considerably
      lower than in uninfected erythrocytes (107.5 versus 161.0) and was very similar
      to that in purified parasites (107.5 versus 98.5). Large increases in palmitic
      acid (C16:0) (from 21.88% to 31.21%) and in oleic acid (C18:1) (from 14.64% to
      24.60%), and major decreases in arachidonic acid (C20:4) (from 17.36% to 7.85%)
      and in docosahexaenoic acid (C22:6) (from 4.34% to 1.8%) occurred as a result of
      infection. The fatty acid profiles of individual phospholipid classes from IEPM
      resembled in many instances the fatty acid profiles of parasite phospholipids
      rather than those of uninfected erythrocytes. Analysis of IEPM from P. falciparum
      infected erythrocytes (trophozoite stage) revealed that, during intra
      erythrocytic maturation of the parasite, the host erythrocyte phospholipid
      composition was markedly refashioned. These alterations were not dependent on the
      method used to isolate the IEPM, with similar results obtained using either a
      saponin-lysis method or binding to Affigel beads. Since mature erythrocytes have
      negligible lipid synthesis and metabolism, these alterations must occur as a
      result of parasite-directed metabolism of erythrocyte lipids and/or trafficking
      of lipids between the parasite and erythrocyte membranes.

PMID- 2001229
TI  - Role of unsaturated derivatives of spermidine as substrates for spermine synthase
      and in supporting growth of SV-3T3 cells.
AB  - Synthetic unsaturated analogues of the natural polyamine were examined as
      possible substrates for spermine synthase and as replacements for spermidine in
      supporting the growth of SV-3T3 cells. It was found that N-(3-aminopropyl)-1,4
      diamino-cis-but-2-ene [the cis isomer of the alkene analogue of spermidine] was a
      good substrate for spermine synthase, but that the trans isomer [N-(3
      aminopropyl)-1,4-diamino-trans-but-2-ene] and the alkene analogue [N-(3
      aminopropyl)-1,4-diaminobut-2-yne] were not substrates. These results provide the
      first demonstration of stereospecificity in the spermine synthase reaction. All
      three of the unsaturated spermidine analogues described above and the cis-alkene
      analogue of spermine [N1N4-bis-(3-aminopropyl)-1,4-diamino-cis-but-2-ene] were
      able to support the growth of SV-3T3 cells that were prevented from the
      endogenous synthesis of spermidine by treatment with alpha
      difluoromethylornithine. Since N-(3-aminopropyl)-1,4-diamino-trans-but-2-ene] and
      N-(3-aminopropyl)-1,4-diaminobut-2-yne were not converted into a spermine
      derivative, it is apparent that this conversion is not needed for the stimulation
      of growth. However, since N1N4-bis-(3-aminopropyl)-1,4-diamino-cis-but-2-ene was
      also able to support growth and was not degraded to the spermidine derivative, it
      appears that either polyamine can be effective in this respect. All of the
      unsaturated analogues tested accumulated in the SV-3T3 cells to a much greater
      extent than spermidine itself. This indicates that these compounds are substrates
      for the polyamine transport system, but that they are less effective than the
      natural polyamines in the feedback regulation of this system.

PMID- 2001228
TI  - Human small-intestinal apolipoprotein B-48 oligosaccharide chains.
AB  - Hepatic apolipoprotein (apo) B-100 isolated from human plasma is known to contain
      N-linked oligosaccharides of high-mannose-type and complex-type structures.
      Sequencing data have revealed that apo B-48 of small-intestinal origin, which
      represents about 48% of apo B-100 polypeptide from the N-terminus, possesses six
      potential sites for N-linked oligosaccharides, of which five are likely to be
      glycosylated. The characterization of the carbohydrate moiety of apo B-48 is the
      focus of this study. Apo B-48 was labelled with L-[35S]methionine and D
      [3H]glucosamine in organ culture of human small-intestinal explants. N-Glycanase
      treatment resulted in loss of radioactivity from D-[3H]glucosamine-labelled but
      not L-[35S]methionine-labelled apo B-48 secreted into the medium, and caused no
      distinct change in mobility of apo B-48 upon electrophoresis on 5% polyacrylamide
      gel. Analysis of monosaccharide content revealed the presence of 16.8, 17.8,
      13.4, 3.4, 2.4 and 2.3 residues of N-acetylglucosamine, mannose, galactose,
      fucose, xylose and N-acetylgalactosamine respectively. Small-intestinal apo B-48
      from human lymph chylomicrons bound to [14C]concanavalin A, and the binding could
      be inhibited with methyl alpha-D-mannoside. In addition, wheat-germ, peanut,
      Limulus, soya-bean and Ulex lectins bound apo B-48 specifically. To characterize
      the carbohydrate moiety further, N-linked oligosaccharides were released by N
      Glycanase treatment and reduced with NaB3H4. Labelled oligosaccharides were
      separated on a concanavalin A-Sepharose column. The majority (78%) were
      biantennary complex-type structures, 16% were high-mannose type and 6% (not
      retained by the column) most probably represented higher-branched
      oligosaccharides. These results suggest the presence of one high-mannose-type and
      four biantennary complex-type oligosaccharides, as well as probable O-linked
      sugars in apo B-48. By the use of h.p.l.c., exoglycosidase treatments and ion
      exchange chromatography, a mixture of high-mannose-type species with predominant
      Man8GlcNAc2 as well as monosialylated, desialylated and fucosylated forms of
      complex-type oligosaccharides were detected.

PMID- 2001230
TI  - The effects of systematic errors on the analysis of irreversible enzyme
      inhibition progress curves.
AB  - The effects of errors in Km and Vmax. on the determination of the kinetic
      constants for the irreversible inhibition of acetylcholinesterase were
      determined. The results show that small errors in the values of Km and Vmax. give
      rise to large errors in the fitted parameters k2 and Kd. The problem may be
      minimized for multiple progress curves by selecting an appropriate number and
      distribution of inhibitor concentrations.

PMID- 2001231
TI  - Physiological glucocorticoid levels regulate glutamine and insulin-mediated
      glucose metabolism in skeletal muscle of the rat. Studies with RU 486
      (mifepristone).
AB  - This study examined the effects of antagonism of the peak level of
      glucocorticoids in vivo, which occurs as rats enter the feeding/activity (dark)
      period on glucose and glutamine metabolism in incubated isolated rat soleus
      muscle preparations. Thus the rats were treated with the potent glucocorticoid
      antagonist RU 486 2 h before and 1 and 2 h into the dark period. Both the content
      of glutamine in skeletal muscle in vivo and plasma glucose and glutamine
      concentrations were elevated midway through the dark period, compared with the
      beginning of the period. RU 486 prevented the increases in plasma glucose and
      glutamine and caused a significant decrease in both the rate of release of
      glutamine in soleus muscle in vitro and the content of glutamine in gastrocnemius
      muscle. The sensitivity of soleus muscle to insulin in vitro is markedly
      decreased when isolated midway through the dark period (i.e. at 03:00 h)
      [Leighton, Kowalchuk, Challiss & Newsholme (1988) Am. J. Physiol. 255, E41-E45].
      We now show that the concentrations of insulin required to stimulate lactate
      formation and glycogen synthesis half-maximally were 95 and 250 muunits/ml
      respectively, and treatment of rats with RU 486 decreased these values to 55 and
      90 muunits of insulin/ml respectively. Thus antagonism of the action of the
      normal circadian rise in the level of glucocorticoids in rats reverses insulin
      insensitivity in soleus muscles in vitro.

PMID- 2001232
TI  - Cytochrome P-450 may link intracellular Ca2+ stores with plasma membrane Ca2+
      influx.
AB  - We have studied the mechanism of the regulation of plasma membrane Ca2+
      permeability by the degree of filling of the intracellular Ca2+ stores. Using
      Mn2+ as a Ca2+ surrogate for plasma membrane Ca2+ channels, we found that Mn2+
      uptake by rat thymocytes is inversely related to the degree of filling of the
      intracellular Ca2+ stores. This store-dependent plasma membrane permeability is
      inhibited by oxygen scavenging, CO, imidazole antimycotics and other cytochrome P
      450 inhibitors. The pattern of inhibition is similar to that reported previously
      for the inhibition of microsomal cytochrome P-450-mediated aryl hydrocarbon
      hydroxylase activity of lymphocytes. Several calmodulin antagonists, both
      phenothiazinic (trifluoperazine, fluphenazine and chlorpromazine) and
      dibenzodiazepinic (clozapine), accelerate Mn2+ uptake by cells with Ca2(+)-filled
      stores, and this effect is prevented by imidazole antimycotics. Our results
      suggest that cytochrome P-450 may be the link between the stores and the plasma
      membrane Ca2+ pathway. We propose a model in which this cytochrome, sited at the
      stores, stimulates plasma membrane Ca2+ influx. This stimulatory effect is, in
      turn, prevented by the presence of Ca2+ inside the stores, possibly via a
      calmodulin-dependent mechanism.

PMID- 2001233
TI  - Mitochondrial gene expression in Saccharomyces cerevisiae. Proteolysis of nascent
      chains in isolated yeast mitochondria optimized for protein synthesis.
AB  - We demonstrate here that mitochondrial translation products synthesized by
      isolated yeast mitochondria are subject to rapid proteolysis. The loss of label
      from mitochondrial peptides synthesized in vitro comes from two distinct pools of
      peptides: one that is rapidly degraded (t1/2 of minutes) and one that is much
      more resistant to proteolysis (t1/2 of hours). As the length of the incubation
      period increases, the percentage of labelled peptides in the rapidly-turning-over
      pool decreases and cannot be detected after 60 min of incubation. This
      proteolysis is inhibited by chloramphenicol and is dependent on the presence of
      ATP. The loss of label during the chase occurs from fully completed translation
      products. The proteolysis observed here markedly affects measurements of rates of
      mitochondrial protein synthesis in isolated yeast mitochondria. In earlier work,
      in which proteolysis was not considered, mitochondrial translation was thought to
      stop after 20-30 min of incubation. In the present study, by taking proteolysis
      into account, we demonstrate that the rate of translation in isolated
      mitochondria is actually constant for nearly 60 min and then decreases to near
      zero by 80 min of incorporation. These findings have allowed us to devise a
      procedure for measuring the 'true' rate of translation in isolated mitochondria.
      In addition, they suggest that mitochondrial translation products which normally
      assemble with nuclear-encoded gene products into multimeric enzyme complexes are
      unstable without their nuclear-encoded counterparts.

PMID- 2001234
TI  - Electron-transfer steps involved in the reactivity of Hansenula anomala
      flavocytochrome b2 as deduced from deuterium isotope effects and simulation
      studies.
AB  - The L-lactate-flavocytochrome b2-ferricyanide electron-transfer system from the
      yeast Hansenula anomala was investigated by rapid-reaction techniques. The
      kinetics of reduction of oxidized flavocytochrome b2 by L-lactate and L
      [2H]lactate were biphasic both for flavin and haem prosthetic groups and at all
      concentrations tested. The first-order rate constants of the rapid and slow
      phases depended upon substrate concentrations, a saturation behaviour being
      exhibited. Substitution of the C alpha-H atom by 2H was found to cause
      appreciable changes in the rate constants for the initial reduction of flavin and
      haem (phase I), which were respectively about 3-fold and 2-fold less than with L
      lactate. In contrast, no significant isotope effect was noted on the apparent
      reduction rate constants of the slow phase, phase II. Under steady-state
      conditions an isotope effect of 2.0 was found on the overall electron transfer
      from L-lactate to ferricyanide. These transient reduction results were discussed
      in terms of a kinetic model implying intra- and inter-protomer electron exchanges
      between flavin and haem b2, all of which have been experimentally described.
      Computer simulations indicate that the reaction scheme provides a reasonable
      explanation of the fast-reduction phase, phase I (in absence of acceptor). The
      pseudo-first-order rate constant for oxidation of reduced haem b2 in
      flavocytochrome b2 increased with increasing ferricyanide concentration in a
      hyperbolic fashion. The limiting value at infinite ferricyanide concentration,
      which was attributed to the intramolecular electron-transfer rate from
      ferroflavocytochrome b2 to the iron of ferricyanide within a complex, was 920 +/-
      50 s-1 at pH 7.0 and 5 degrees C. Stopped-flow and rapid-freezing measurements
      showed haem b2 and flavin to be 90 and 44% oxidized respectively under steady
      state conditions in presence of ferricyanide. Simulation studies were carried out
      to check the participation of the proposed reduction sequence in the overall
      catalytic reaction together with the role of reduced haem b2 (Hr) and flavin
      semiquinone (Fsq) as electron donors to ferricyanide. When the rate of the
      intramolecular electron-transfer exchange between Fsq and ferricyanide was
      adjusted to 200 s-1, simulated data accounted for molar activities defined under
      various conditions of L-lactate, [2H]lactate and ferricyanide concentrations.
      Simulation studies were extended to data obtained using cytochrome c as acceptor
      and reaction catalysed by Saccharomyces cerevisiae flavocytochrome b2. The
      differences in reactivity observed for Hr and Fsq with ferricyanide and
      cytochrome c were discussed in terms of redox potentials, electrostatic
      interactions, distances and accessibility of the participating groups.

PMID- 2001235
TI  - Regulation of fatty acid metabolism and gluconeogenesis by growth hormone and
      insulin in sheep hepatocyte cultures. Effects of lactation and pregnancy.
AB  - Primary monolayer hepatocyte cultures derived from non-mated, pregnant and
      lactating sheep were used to investigate the interactions between the effects of
      growth hormone and insulin on (i) the partitioning of fatty acid metabolism
      between oxidation and esterification, and (ii) the rate of gluconeogenesis. In
      hepatocytes from lactating sheep the rates of gluconeogenesis, ketogenesis and
      very-low-density lipoprotein secretion were approx. 2-fold higher than in cells
      from non-mated or pregnant animals. There was no apparent difference in the rates
      of fatty acid uptake between the three groups of sheep cells. Growth hormone
      stimulated gluconeogenesis only in hepatocytes from non-mated sheep. It has no
      effect on the flux of fatty acid towards ketone body formation. Growth hormone
      inhibited intracellular accumulation of acylglycerol from exogenous fatty acid.
      Insulin alone had no such effect, but it blunted the effect of growth hormone
      when the two hormones were present together. The data suggest that major
      differences may exist between ruminants and non-ruminants in the response of
      liver metabolism both to lactation per se and to the effects of growth hormone
      and insulin.

PMID- 2001237
TI  - The role of cysteine-150 in the structure and activity of rat liver S-adenosyl-L
      methionine synthetase.
AB  - The present paper reports the tryptic digestion of N-ethylmaleimide-treated S
      adenosyl-L-methionine synthetase (high- and low-Mr forms) and the isolation of
      the modified peptides by h.p.l.c. There is only one site modified after 5 min
      incubation, and the modification at this site correlates with the main activity
      decrease. The amino acid composition of this peptide was determined, and its
      localization in the sequence shows the modified residue as cysteine-150, which is
      located close to the putative ATP-binding site. Modification of the enzyme for 20
      min led to the appearance of a second labelled peptide, which seems to be
      responsible for about a further 10% of the activity loss. The modification by N
      ethylmaleimide of the enzyme was partially prevented in the presence of adenosine
      5'-[beta gamma-imido]triphosphate and methionine, further supporting the
      hypothesis that the modified residues lie within the active site. Urea treatment
      of the enzyme, followed by modification with N-ethylmaleimide, produces the
      modification of 7 of the 10 cysteine residues present in the sequence. The
      results obtained were the same for either of the isoforms.

PMID- 2001236
TI  - The major proteoglycan of adult rabbit skeletal muscle. Relationship to small
      proteoglycans of other tissues.
AB  - We have been interested in examining the putative biological role(s) of the major
      proteoglycan of adult skeletal muscle. The small proteoglycans of adult rabbit
      skeletal muscle and tendon were extracted and purified by sequential density
      gradient ultracentrifugation, ion-exchange chromatography and gel filtration.
      They appeared to be homogeneous by the criterion of gel electrophoresis in SDS
      and to yield one major product, the core protein, after digestion with
      chondroitin ABC lyase, also observed after gel electrophoresis. Two major
      products were obtained when the intact proteoglycans were cleaved by CNBr, and
      those peptides were separated by SDS/PAGE and by ion-exchange chromatography.
      Sequencing of the N-terminal amino acids of either the intact proteoglycans or
      the CNBr-cleaved products allowed for comparison of the muscle and tendon
      proteoglycan with derived amino acid sequences previously reported for bovine
      bone proteoglycan. The bone and tendon proteoglycan sequences were remarkably
      similar, whereas those of the muscle proteoglycan differed from the other two
      molecules. The major site of glycosaminoglycan substitution was on a peptide
      fragment distant from the N-terminus, and a presumptive serine residue at
      position 4 from the N-terminus also appeared to be substituted, perhaps with a
      small glycosaminoglycan chain. These results provide some insight into the
      diversity of small proteoglycans of the PG-II class and provide a basis for
      exploring their mode of genetic expression.

PMID- 2001238
TI  - Purification and characterization of thaumatopain, a cysteine protease from the
      arils of the plant Thaumatococcus daniellii.
AB  - Aqueous extracts of the aril of the seed of Thaumatococcus daniellii contain, in
      addition to the intensely sweet protein thaumatin, a cysteine protease that we
      have termed thaumatopain. Thaumatopain has been purified by ion-exchange
      chromatography from arils, and is a monomeric protein of Mr 30,000. The protease
      strongly resembles papain in proteolytic activity, pH optima, susceptibility to
      inhibitors of cysteine proteases and in N-terminal sequence. The protease has
      also been identified in crude aril extracts by affinity labelling with
      iodo[14C]acetate. Thaumatopain is responsible for the cysteine protease activity
      previously attributed to thaumatin. Thaumatin is digested by thaumatopain at
      neutral to alkaline pH values.

PMID- 2001239
TI  - Uptake and degradation of filamentous actin and vitamin D-binding protein in the
      rat.
AB  - Tissue uptake and degradation of 125I-tyramine-cellobiose-labelled filamentous
      actin, vitamin D-binding protein (DBP) and actin-DBP complex were studied in the
      rat. Actin and actin-DBP complex were cleared from plasma at a faster rate than
      was DBP. About 40% of injected actin was recovered in the liver between 10 and 30
      min after administration. Of the total radioactivity recovered in the liver,
      about 35% and 40% was detected in parenchymal and endothelial cells respectively
      when labelled actin or DBP-actin complex was injected intravenously. When
      labelled DBP alone was injected, approx. 55% of the radioactivity recovered in
      liver was in the Kupffer cells. These results suggest that actin is targeting the
      DBP-actin complex to the endothelial and parenchymal liver cells. Filamentous
      actin was also taken up in large amounts and at a rapid rate in parenchymal as
      well as non-parenchymal liver cells in vitro. Our data indicate that the rat has
      a mechanism to clear actin and the DBP-actin complex from plasma and that both
      parenchymal and non-parenchymal liver cells are involved in this process.

PMID- 2001240
TI  - Cellular mechanisms of adrenaline-induced hyperpolarization in renal epitheloid
      MDCK cells.
AB  - The effects of adrenaline on the potential difference across the cell membrane,
      on formation of inositol phosphates and on intracellular Ca2+ ([Ca2+]i) were
      analysed in cells without or with pretreatment with pertussis toxin or phorbol 12
      myristate 13-acetate (PMA). In untreated cells, adrenaline leads to a sustained
      hyperpolarization, a stimulation of Ins(1,4,5)P3 and Ins(1,3,4,5,)P4 formation
      and a transient increase in [Ca2+]i from 78 +/- 7 to 555 +/- 43 nM, followed by a
      plateau of 260 +/- 23 microM. In the absence of extracellular Ca2+ the effect of
      adrenaline on both potential difference and [Ca2+]i is transient. In cells
      pretreated with pertussis toxin, the effects of adrenaline on InsP3 and [Ca2+]i
      are still preserved, but the effect on potential difference is transient. In
      cells pretreated with PMA, the effect of adrenaline on InsP3 formation is
      severely decreased and that on [Ca2+]i abolished, whereas a transient
      hyperpolarizing effect is still present. This transient hyperpolarization is
      abolished by additional pretreatment with pertussis toxin. The observations
      suggest that adrenaline hyperpolarizes the cell membrane of MDCK cells by several
      distinct mechanisms. First, adrenaline stimulates the formation of InsP3 and
      InsP4, which at least in part accounts for the release of intracellular Ca2+ and
      the entry of Ca2+ from the extracellular fluid. Stimulation of phospholipase C is
      not mediated by pertussis-toxin-sensitive G-proteins, but apparently is inhibited
      by activation of protein kinase C. Second, adrenaline hyperpolarizes the cell
      membrane by a mechanism independent from increase in [Ca2+]i which is sensitive
      to pertussis toxin but is, at least in part, insensitive to PMA.

PMID- 2001241
TI  - Succinate-driven reverse electron transport in the respiratory chain of plant
      mitochondria. The effects of rotenone and adenylates in relation to malate and
      oxaloacetate metabolism.
AB  - The effects of rotenone on the succinate-driven reduction of matrix nicotinamide
      nucleotides were investigated in Percoll-purified mitochondria from potato
      (Solanum tuberosum) tubers. Depending on the presence of ADP or ATP, rotenone
      caused an increase or a decrease in the level of reduction of the matrix
      nicotinamide nucleotides. The increase in the reduction induced by rotenone in
      the presence of ADP was linked to the oxidation of the malate resulting from the
      oxidation of succinate. Depending on the experimental conditions, malic enzyme
      (at pH 6.6 or in the presence of added CoA) or malate dehydrogenase (at pH 7.9)
      were involved in this oxidation. At pH 7.9, the oxaloacetate produced
      progressively inhibited the succinate dehydrogenase. In the presence of ATP the
      production of oxaloacetate was stopped, and succinate dehydrogenase was protected
      from inhibition by oxaloacetate. However, previously accumulated oxaloacetate
      transitorily decreased the level of the reduction of the NAD+ driven by
      succinate, by causing the reversal of the malate dehydrogenase reaction. Under
      these conditions (i.e. presence of ATP), rotenone strongly inhibited the
      reduction of NAD+ by succinate-driven reverse electron flow. No evidence for an
      active reverse electron transport through a rotenone-insensitive path could be
      obtained. The inhibitory effect of rotenone was masked if malate had previously
      accumulated, owing to the malate-oxidizing enzymes which reduced part or all of
      the matrix NAD+.

PMID- 2001242
TI  - Purification of a serine-proteinase inhibitor from human articular cartilage.
      Identity with the acid-stable proteinase inhibitor of mucous secretions.
AB  - An inhibitor of the serine proteinases human leucocyte elastase (EC 3.4.21.37),
      of cathepsin G (EC 3.4.21.20) and of trypsin (EC 3.4.21.4) has been purified from
      human articular cartilage. The apparent Mr of the cationic (pI greater than 10)
      protein was determined to 15,000 by SDS/PAGE. It was shown to cross-react in
      Western blot with a specific antibody to a recombinant-derived serine-proteinase
      inhibitor of human mucous secretions. Identity of both inhibitors is indicated by
      the determination of the N-terminal amino acid sequence of the cartilage-derived
      serine-proteinase inhibitor. In all 24 residues the cartilage inhibitor was shown
      to be identical with the human secretory leucocyte proteinase inhibitor ('SLPI').
      The inhibitor molecule may play a crucial role in the protection of cartilage
      matrix proteins against proteolytic attack.

PMID- 2001243
TI  - Multiple sodium-dependent nucleoside transport systems in bovine renal brush
      border membrane vesicles.
AB  - Na(+)-dependent nucleoside transport was examined in bovine renal brush-border
      membrane vesicles. Two separate Na+/nucleoside cotransporters were shown to be
      present: (1) a system specific for purine nucleosides and uridine, designated as
      the N1 carrier, and (2) an Na(+)-dependent nucleoside transporter that accepts
      pyrimidine nucleosides, adenosine and analogues of adenosine, designated as the
      N2 system. Both systems exhibit a high affinity for nucleosides (apparent Km
      values approximately 10 microM), are insensitive to inhibition by facilitated
      diffusion nucleoside transport inhibitors, are rheogenic and exhibit a high
      specificity for Na+. Na+ increases the affinity of the influx of guanosine and
      thymidine, nucleosides that serve as model permeants for the N1 and N2 nucleoside
      transporters respectively. The Na+/nucleoside coupling stoichiometry is
      consistent with 1:1 for both carriers.

PMID- 2001245
TI  - Pseudoperoxidase activity of 5-lipoxygenase stimulated by potent benzofuranol and
      N-hydroxyurea inhibitors of the lipoxygenase reaction.
AB  - The purified 5-lipoxygenase from porcine leukocytes was found to catalyse the
      degradation of lipid hydroperoxides in the presence of potent inhibitors of the
      lipoxygenase reaction. Derivatives of diphenyl-N-hydroxyureas, 4
      hydroxybenzofurans and 5-hydroxydihydrobenzofurans all stimulated the 5
      lipoxygenase-mediated destruction of 13-hydroperoxyoctadecadienoic acid (13
      HPOD). The reaction was dependent on inhibitor and hydroperoxide concentrations
      (1-10 microM) and could not be detected using heat-inactivated enzyme, when ATP
      and Ca2+ were omitted or when the hydroperoxide was replaced by the corresponding
      alcohol. The stability of the inhibitors during this pseudoperoxidase reaction
      was investigated by measuring the recoveries of 5-hydroxy-2-phenethyl-6-(3
      phenoxypropyl)-2,3-dihydrobenzofuran and N-(4-chlorophenyl)-N-hydroxy-N'-(3
      chlorophenyl)urea from the reaction mixtures using reverse-phase h.p.l.c. By
      using an equimolar concentration of 13-HPOD and inhibitor (10 microM) and under
      conditions where 50% of the 13-HPOD was consumed, the concentration of the
      benzofuranol decreased by 30%, whereas the N-hydroxyurea derivative could be
      completely recovered from the reaction mixture. A stimulation of the
      pseudoperoxidase reaction could be detected only with very effective inhibitors
      of leukotriene B4 biosynthesis by human leucocytes [IC50 (concn. causing 50%
      inhibition) less than 100 nM], but not with closely related structural analogues
      of lower potency or other inhibitors such as nordihydroguaiaretic acid, quercetin
      or the hydroxamate A-64077. These results demonstrate that 5-lipoxygenase
      possesses a pseudoperoxidase activity and indicate that potent inhibitors in both
      N-hydroxyurea and benzofuranol series can function as reducing agents for the
      enzyme.

PMID- 2001244
TI  - Inhibition of glutathione-conjugate secretion from isolated hepatocytes by
      dipolar bile acids and other organic anions.
AB  - The effect of a spectrum of organic compounds on the secretion of a model organic
      anion, dinitrophenylglutathione (GS-DNP), by hepatocytes was tested. Previous
      experiments have demonstrated that the secretion of GS-DNP from isolated rat
      hepatocytes is predominantly mediated by a canalicular transport system for this
      compound. Preincubation of isolated rat hepatocytes with the bile acids cholic
      acid (C), taurocholic acid (TC), tauroursodeoxycholic acid (TUDC) and glyco- or
      tauro-lithocholic acid (GLC or TLC) had no effect on the initial efflux rate of
      GS-DNP. In contrast, the 3-sulphates of GLC (SGLC) and TLC (STLC) did inhibit GS
      DNP efflux; half-maximal inhibition with SGLC was reached with 10 microM. The 3-O
      glucuronides of both cholate and lithocholate (GlucLC) were even more potent
      inhibitors of transport; 10 microM-GlucLC inhibited GS-DNP transport by 89%.
      Other cholephilic organic anions also inhibited GS-DNP secretion, albeit at
      higher concentrations; at 100 microM, bilirubin ditaurate, an analogue of
      bilirubin diglucuronide, inhibited transport by 48%. On the other hand, a number
      of cholephilic cationic and neutral compounds had no effect on GS-DNP efflux. The
      hepatobiliary secretion of oxidized glutathione (GSSG) was also investigated. In
      normal isolated perfused rat liver, extensive biliary secretion of GSSG was
      observed upon intracellular oxidation of reduced glutathione (GSH). GSSG was also
      actively secreted from isolated normal hepatocytes, and this secretion could be
      inhibited by 95% by incubation of the cells with 100 microM-SGLC. In contrast,
      biliary secretion was absent in the isolated perfused liver and in isolated
      hepatocytes from TR- mutant rats with a hereditary conjugated
      hyperbilirubinaemia. These results show that the canalicular efflux of GSSG and
      GS conjugates can be inhibited by a wide variety of polyvalent organic anions,
      but not by cations, neutral compounds and unianionic bile acids. This suggests
      that a multispecific organic-anion transporter is responsible for transport of
      these polyvalent anions, which is in close agreement with the fact that the
      biliary transport of all these compounds is defective in the mutant TR4 rat.

PMID- 2001246
TI  - The effects of selenium deficiency on hepatic type-I iodothyronine deiodinase and
      protein disulphide-isomerase assessed by activity measurements and affinity
      labelling.
AB  - We determined protein disulphide-isomerase (PDI) and iodothyronine deiodinase (ID
      I) activities in liver homogenates from rats subjected to selenium (Se) and/or
      iodine deficiencies and food restriction. Additionally, the effects of
      propylthiouracil (PTU) on the enzymes were studied in vivo and in vitro. Selenium
      deficiency markedly inhibited ID-I activity, but had no significant effects on
      PDI. Iodine deficiency resulted in a 1.6-fold stimulation in ID-I and a 1.2-fold
      stimulation in PDI activities. ID-I was much more sensitive than PDI to the
      inhibitory effects of PTU both in vitro and in vivo. By using a 3,3',5'
      tri[125I]iodothyronine affinity label, two major protein bands were identified
      when hepatic microsomal fractions from Se-sufficient rats were subjected to
      SDS/PAGE and autoradiography. These bands had molecular masses of 55 and 27.5
      kDa, which are similar to those of PDI and ID-I respectively. Selenium deficiency
      resulted in the loss of the 27.5 kDa band, but did not affect the intensity of
      the 55 kDa band. These results are consistent with the changes in PDI and ID-I
      enzyme activities. Previous studies have shown that 75Se may be incorporated in
      vivo into the 27.5 kDa protein band. This, taken together with our observation
      that Se is required for the expression of ID-I and the 27.5 kDa protein band,
      strongly suggests that ID-I is a selenoprotein.

PMID- 2001247
TI  - Stability of mutant actins.
AB  - Mutants of the Drosophila Act88F actin gene were transcribed and translated in
      vitro and their relative stabilities were examined using urea gradient gel
      electrophoresis. Most of the mutant actins (E334K, E364K, G366D, G368E and R372H)
      were as stable as the wild-type. V339I had a slight decrease in stability, and
      E316K was the least stable. The causes of the differences are discussed and
      contrasted with the behaviour of the mutants in vivo, where E316K has normal
      stability and V339I is the least stable.

PMID- 2001248
TI  - Purification and properties of dimethyl sulphoxide reductase from Rhodobacter
      capsulatus. A periplasmic molybdoenzyme.
AB  - Dimethyl sulphoxide reductase was purified from the photosynthetic bacterium
      Rhodobacter capsulatus. The enzyme is composed of a single polypeptide of Mr
      82,000 and contains a pterin-type molybdenum cofactor as the only detectable
      prosthetic group. The oxidized molybdenum cofactor of dimethyl sulphoxide
      reductase is a weak chromophore and exhibits broad absorption bands in the u.v.
      visible-absorption spectral region. A distinct spectrum was generated upon
      addition of dithionite.

PMID- 2001249
TI  - Prostaglandins E2 and F2 alpha increase fructose 2,6-bisphosphate levels in
      isolated hepatocytes.
AB  - In hepatocytes isolated from fed rats, prostaglandin E2 (PGE2) and prostaglandin
      F2 alpha (PGF2 alpha) increased, in a time- and dose-dependent manner, fructose
      2,6-bisphosphate [Fru(2,6)P2] levels and stimulated the glycolytic flux. The rise
      in Fru(2,6)P2 was related to an increase in glucose 6-phosphate levels which
      resulted from the stimulation of glycogenolysis. In cells obtained from 24 h
      starved rats, no effects of either PGE2 or PGF2 alpha could be observed. In
      addition, when the stimulation of glycogenolysis was abolished by incubation of
      fed-rat hepatocytes in a Ca2(+)-depleted medium, Fru(2,6)P2 levels did not
      increase. Furthermore, no effects of PGs on 6-phosphofructo-2-kinase activity
      could be observed. These results indicate that PGE2 and PGF2 alpha show similar
      actions to Ca2(+)-dependent hormones on hepatic glucose metabolism.

PMID- 2001250
TI  - A quenched fluorescent substrate for thimet peptidase containing a new
      fluorescent amino acid, DL-2-amino-3-(7-methoxy-4-coumaryl)propionic acid.
AB  - DL-2-Amino-3-(7-methoxy-4-coumaryl)propionic acid, a new fluorescent amino acid
      (abbreviated to Amp), has been synthesized to provide an alternative to
      tryptophan in quenched fluorescent peptide substrates for peptidases. The model
      compound Ac-DL-Amp-NH2 was intensely fluorescent with an excitation maximum at
      328 nm and an emission maximum at 392 nm. Fmoc (fluoren-9-ylmethoxycarbonyl)-DL
      Amp was made to allow the solid-phase synthesis of Amp-containing peptides by the
      Fmoc-polyamide method. The peptide derivative Dnp (2,4-dinitrophenyl)-Pro-Leu-Gly
      Pro-DL-Amp-D-Lys was cleaved by thimet peptidase at the Leu-Gly bond, with a 20
      fold enhancement of fluorescence. The value of kcat./Km for thimet peptidase was
      6.7 x 10(5) M-1.s-1, compared with the value of 2.4 x 10(5) M-1.s-1 for the
      tryptophan-containing analogue, Dnp-Pro-Leu-Gly-Pro-Trp-D-Lys.

PMID- 2001251
TI  - Extracellular ATP-induced acidification leads to cytosolic calcium transient rise
      in single rat cardiac myocytes.
AB  - The origin of the increase in cytosolic free Ca2+ concentration ([Ca2+]i) induced
      by extracellular ATP was investigated in single isolated cardiac myocytes loaded
      with indo-1. The nucleotide added at a concentration of 10 microM triggers a few
      Ca2+ spikes, followed by a cluster of Ca2+ oscillations, increasing [Ca2+]i to
      around 200 nM from a basal value of 70 nM. Neither caffeine nor ryanodine affects
      the magnitude of the Ca2+ transient, but both shorten it by preventing the Ca2+
      oscillations. This indicates that the latter must be related to the release of
      Ca2+ from the sarcoplasmic reticulum. Since ATP also induces cell depolarization
      (as shown by experiments using the potential sensitive dye bis-oxonol), the
      initial Ca2+ spikes were attributed to the opening of voltage-dependent Ca2+
      channels. A small Ca2+ transient still remains under experimental conditions
      designed to prevent Ca2+ influx from external medium (low-Ca2+ high-Mg2+ medium
      containing La3+) and after depletion of the sarcoplasmic-reticulum Ca2+ load with
      caffeine. Under these conditions, when this Ca2+ transient was buffered by 1,2
      bis-(O-aminophenoxy)ethane-NNN'N'-tetra-acetic acid, ATP was unable to trigger
      the initial Ca2+ spikes. These results indicate that ATP mobilizes Ca2+ ions from
      an intracellular pool other than the sarcoplasmic reticulum and that this Ca2+
      release is responsible for the depolarization. The effects of ATP on [Ca2+]i
      share the same characteristics as the acidification simultaneously induced by the
      nucleotide (as shown by experiments using the pH-sensitive probe snarf-1). These
      ionic variations are highly specific to ATP and its hydrolysis-resistant
      analogues. They both require the presence of Mg2+ and Cl- ions in the
      extracellular medium, and they are prevented by pretreatment of the cells with
      4,4'-di-isothiocyanostilbene or probenecid. These results suggest that: (1) the
      ATP-induced acidification leads to displacement of Ca2+ ions from or close to the
      internal face of sarcolemma; (2) the Ca2+ ions activate a non-specific membrane
      conductance responsible for the depolarization of the cells; (3) the
      depolarization leads to a Ca2+ influx, owing to the opening of the voltage
      dependent Ca2+ channels; (4) this increase in Ca2+ triggers the release of Ca2+
      from the sarcoplasmic reticulum, which is facilitated by the increase in inositol
      trisphosphate following P2-purinergic stimulation.

PMID- 2001252
TI  - Assignment of disulphide bonds in human platelet GPIIIa. A disulphide pattern for
      the beta-subunits of the integrin family.
AB  - Integrins are cell-surface heterodimers formed by the association of one alpha-
      and one beta-subunit. Glycoprotein IIIa (GPIIIa or beta 3 subunit) is the common
      beta-subunit of the beta 3 subfamily of integrins, which, when associated with
      glycoprotein IIb (GPIIb), constitutes the receptor for fibrinogen and other
      adhesive proteins at the platelet surface (the GPIIb-IIIa complex) and, when
      associated with the alpha v-subunit, constitutes the vitronectin receptor present
      in several cell types. Protein chemical analysis of GPIIIa allows us to define
      the following structural domains: the cysteine-rich and proteinase-resistant N
      terminal domain (GPIIIa 1-62); the adhesive-protein-binding domain (GPIIIa 101
      422); the cysteine-rich and proteinase-resistant core (GPIIIa 423-622); and the C
      terminal domain comprising an extracellular subdomain (GPIIIa 623-692), a
      transmembrane subdomain (GPIIIa 693-721), and a cytoplasmic subdomain (GPIIIa 722
      762). We also assign unambiguously the disulphide bonds within the N-terminal,
      the fibrinogen-binding and the C-terminal domains, and the two long-range
      disulphide bonds which join the N-terminus to the proteinase-resistant core (Cys5
      Cys435) and the fibrinogen-binding domain to the extracellular side of the C
      terminal domain (Cys406-Cys655). In addition, we propose three alternative models
      for the arrangement of the disulphide bonds within the core and of the disulphide
      bonds joining the core to the extracellular side of the C-terminal domain,
      consistent with our experimental findings, favouring temporarily that which
      imposes less steric hindrance for the formation of these disulphide bonds. On the
      basis of this information and on the highly conserved overall structure observed
      in the beta-subunits of the integrin family known so far, except in beta 4, we
      propose to extend the cysteine-pairing pattern and the structural domains
      outlined here for GPIIIa to all the beta-subunits of the integrin family.

PMID- 2001253
TI  - Insulin secretory granule biogenesis. Co-ordinate regulation of the biosynthesis
      of the majority of constituent proteins.
AB  - Two-dimensional gel-electrophoretic analysis combined with fluorography and
      densitometric quantification was used to examine the effects of glucose on the
      biosynthesis of rat pancreatic islet proteins. An increase in the medium glucose
      concentration from 2.8 to 16.7 mM produced a 10-20 fold stimulation in the
      synthesis of 10 out of 260 detected islet proteins, as judged by incorporation of
      [35S]methionine during a 20 min incubation. The synthetic rates of the majority
      of the remaining proteins were stimulated by 2-4-fold. Greater resolution
      achieved by pulse-chase labelling and subcellular fractionation showed that, of
      32 major proteins localized to insulin secretory granules, the biosynthesis of 25
      were stimulated 15-30-fold by glucose. By contrast, only eight of 160 proteins in
      the soluble fraction showed a response of similar magnitude. It is concluded that
      there is a major and co-ordinated activation of the biosyntheses of proteins
      destined for secretory granules, which most likely occurs at the level of
      translational initiation and signal-recognition-particle-mediated translocation
      into the endoplasmic reticulum lumen. However, it is clear that not all granule
      proteins, or the majority of proteins translocated across the endoplasmic
      reticulum membrane, are affected in an equivalent manner. In addition, the
      synthesis of a small number of cytosolic proteins may be increased markedly by
      insulinotropic stimuli.

PMID- 2001255
TI  - Induction of the differentiation of HL-60 cells by phorbol 12-myristate 13
      acetate activates a Na(+)-dependent uridine-transport system. Involvement of
      protein kinase C.
AB  - The Na(+)-dependent transport and facilitated diffusion of uridine were measured
      after differentiation of HL-60 leukaemia cells along the monocytic pathway by
      phorbol 12-myristate 13-acetate (PMA). PMA (200 ng/ml) caused a marked increase
      in Na(+)-dependent uridine transport within 48 h of exposure that was
      attributable to an increase in transport affinity (apparent Km values of 1.15 +/-
      0.22 and 44 +/- 4.4 microM for PMA-induced and uninduced cells respectively),
      with no change in Vmax. (0.15 +/- 0.02 and 0.13 +/- 0.01 pmol/s per microliter of
      cell water for PMA-induced and uninduced cells respectively). A corresponding
      rapid decrease in both the rate of facilitated diffusion and the formation of
      uracil nucleotides occurred in PMA-induced cells. As a consequence of these
      changes, intracellular pools of uridine 3-4-fold greater than those in the medium
      were generated. A similar increase in Na(+)-dependent transport of adenosine,
      inosine, guanosine, thymidine and cytidine (Km values of 1-4 microM) was
      observed. The effects of PMA on the activation of the Na(+)-dependent uridine
      transporter were inhibited by staurosporine, suggesting the involvement of
      protein kinase C. The findings indicate that a change in the balance of the
      cellular mechanisms employed for nucleoside transport occurs during the monocytic
      differentiation of HL-60 leukaemia cells.

PMID- 2001254
TI  - The lobster carapace carotenoprotein, alpha-crustacyanin. A possible role for
      tryptophan in the bathochromic spectral shift of protein-bound astaxanthin.
AB  - Crustacyanin, cross-linked with dimethyl pimelimidate to stabilize the protein
      against denaturation, was used to test the effects of tryptophan modification
      with BNPS-skatole [3-bromo-3-methyl-2-(nitrophenylmercaptol)-3H-indole] on the
      ability of the apoprotein to recombine with astaxanthin. The cross-linked
      apoprotein re-forms alpha-crustacyanin with astaxanthin in reasonable yield
      following incubation of the protein under the conditions for tryptophan
      modification in the absence of BNPS-skatole. The BNPS-skatole-treated protein
      reconstitutes with astaxanthin to give a carotenoprotein with lambda max. at 472
      nm, that of the carotenoid in hexane, in a yield similar to that of the BNPS
      skatole-untreated control. The implied involvement of tryptophan residues at the
      sites of astaxanthin attachment in crustacyanin and their possible roles in the
      binding sites of vitamin A in vitamin A-proteins are discussed in relation to the
      bathochromic spectral shifts of the chromophores.

PMID- 2001256
TI  - Gly429 is the major determinant of uncompetitive inhibition of human germ cell
      alkaline phosphatase by L-leucine.
AB  - The catalytic activity of human placental alkaline phosphatase (PLAP) and germ
      cell alkaline phosphatase (GCAP) can be inhibited, through an uncompetitive
      mechanism, by L-Phe. GCAP is also selectively inhibited by L-Leu. Site-directed
      mutagenesis of five of the 12 residues which are different in PLAP and GCAP
      revealed that Gly429 is the primary determinant of GCAP inhibition by L-Leu, and
      Ser84 and Leu297 play a modulatory role in the inhibition.

PMID- 2001258
TI  - ASHA interviews Patrick J. Carney 1991 President.

PMID- 2001257
TI  - Functional reconstitution of the hepatic system N amino acid transport activity.
AB  - Hepatic System N is responsible for the active plasma-membrane transport of
      glutamine, histidine and asparagine. This report describes the solubilization and
      reconstitution of System N activity. Differential solubility resulted in an
      approximate enrichment of almost 600-fold compared with total cell homogenate.
      The results indicate that reconstitution can be utilized as a functional assay
      during purification of the hepatic System N carrier protein.

PMID- 2001259
TI  - Doctor or doctor? A choice of guilds.

PMID- 2001260
TI  - Observations on preprofessional education: is there a "major" difference?

PMID- 2001261
TI  - Preprofessional-only program: a fruitful endeavor.

PMID- 2001262
TI  - Listening to the voices of the new majority--reentry and returning women.

PMID- 2001263
TI  - A study of ASHA's Award for Continuing Education (ACE).

PMID- 2001264
TI  - The audiologist's responsibility in cerumen management.

PMID- 2001265
TI  - Use of BITNET in communication disorders training programs.

PMID- 2001266
TI  - An introduction to product line management.
AB  - Management by product line has been used successfully in the manufacturing
      industry for decades. As the healthcare industry evolves, implementation of
      Product Line Management is emerging as one strategy to increase efficiency,
      effectiveness, and profitability. Product Line Management is an organizational
      scheme and alternative management system for focusing on the programmatic scope
      of operations in order to achieve particular objectives. Product Line Management
      in a hospital setting requires deviation from linear functional management
      paradigms to a reorganization in thinking that focuses on end-result objectives.
      This management structure recognizes the need to integrate operational and
      clinical management in response to market-driven forces from both the standpoint
      of packaging products for the marketplace and appropriate management of those
      products to improve organizational effectiveness and profitability. However, a
      "test of time" is necessary to evaluate whether Product Line Management has a
      positive impact on clinical intervention and outcome. Although Product Line
      Management seems to be a method to increase profitability, its effect on the
      quality of client care remains unclear. Speech-language pathologists and
      audiologists need to be well informed about Product Line Management in the
      healthcare industry, and should prepare for the possibility of participating
      within such a framework. Finally, speech-language pathologists and audiologists
      need to examine and consider their particular qualifications for assuming
      leadership within such a structure.

PMID- 2001267
TI  - A profile of ASHA members in private practice.

PMID- 2001268
TI  - Proposed revision of code of ethics. American Speech-Language-Hearing
      Association.

PMID- 2001269
TI  - Splenic artery aneurysm rupture.
AB  - Splenic artery aneurysms are rare and usually asymptomatic. However, rupture can
      produce severe abdominal pain and prove lethal. Two cases of ruptured splenic
      artery aneurysm are presented. In one, cocaine injection occurred immediately
      prior to the onset of symptoms and may have precipitated the event.

PMID- 2001270
TI  - Occupational health nursing education. Curricular content in baccalaureate
      programs.
AB  - It is important that occupational health nursing content be offered in academic
      institutions to support the scope of practice in the specialty. Less than 50% of
      the schools responding (N = 215) included content specific to occupational health
      nursing concepts and practice, related fields of knowledge, and management of the
      occupational health unit. Occupational health nurses in practice settings and
      educational institutions should collaborate on the development of occupational
      health content in nursing school curricula.

PMID- 2001271
TI  - Heart healthy education. Effectiveness of teaching methods in the workplace.
AB  - One fourth to one third of employed workers in this country have at least one of
      three major risk factors for coronary heart disease. This pilot study examined
      differences between educational methods used in an occupational setting. The
      specific aims of the quasi-experimental study were: to determine differences
      between two groups of subjects who received either group support and instruction
      or only written instruction; and to determine the association between the
      practice of heart healthy behaviors and decreased blood cholesterol levels. No
      significant differences were found between the two groups in cholesterol and
      behavior changes. However, there was a significant difference between pre- and
      post-instruction for all subjects. The study documented significant changes in
      cholesterol levels, cholesterol and fat intake, and weight reduction.

PMID- 2001272
TI  - Future preparation of occupational health nurse managers.
AB  - This article presents the results of a national survey of job activities of
      corporate level occupational health nurse managers. The survey was designed to
      identify the relative amount of time spent and importance attributed to specific
      areas of their current job. In general this sample tended to have more management
      experience and educational preparation than previously cited studies: over 50%
      had completed a graduate degree. The scores for importance and time spent were
      highly correlated. That is, occupational health corporate nurse managers seemed
      to allocate their time to job responsibilities they considered most important.
      Management activities related to policy, practice standards, quality assurance,
      staff development, and systems for client care delivery appear to represent the
      core responsibilities of occupational health nursing management. Curriculum
      recommendations for management positions in occupational health include: health
      policy, program planning, and evaluation; business strategy; applications of
      management information systems; quality assurance; and marketing.

PMID- 2001273
TI  - Ergonomics and the occupational health nurse. Instituting a workplace program.
AB  - The science of ergonomics is fairly new to industry. It encompasses the total
      physiological and psychological demands of the job on the employee. Through
      observations and recordkeeping, the occupational health nurse can note trends in
      range of motion illnesses related to specific job functions and specific
      employees. Ergonomic approaches are the same as with other hazardous situations:
      engineering, administrative controls, and employee training. As a member of the
      occupational safety and health team, the occupational health nurse plays a vital
      role in preventing mental and physical fatigue and promoting worker health.

PMID- 2001274
TI  - Comparison of four behavioral theories. A literature review.
AB  - A major concern among occupational health nurses is the efficacy of their health
      education and health promotion programs. The success of programs may be improved
      when they are built on a sound and appropriate theoretical foundation. Four
      models that present a logical and reasonable approach to behavioral change
      include the Health Belief Model, the Theory of Self Efficacy, the Theory of
      Reasoned Action, and the Multiattribute Utility Model. Behavioral models provide
      a framework for the development of interventions and strategies which will
      facilitate behavioral change.

PMID- 2001275
TI  - Improving work performance.

PMID- 2001276
TI  - Improving on BCG.
AB  - BCG is the only vaccine for tuberculosis and leprosy known to be effective in at
      least some places. Unfortunately it tends to be less successful in just those
      areas of the developing world where a vaccine is most needed. Although molecular
      biology offers the prospect of alternatives, these still lie in the indefinite
      future, and the best use has to be made of BCG. A number of preparations are
      available from different manufacturers, and a vaccine should be selected with
      good evidence of efficacy, and a low incidence of complications. Selection of the
      optimal age for administering BCG should be based on factors pertaining in the
      area where it is to be used. The influence of contact with environmental
      mycobacteria, the age at which mycobacterial diseases occur, and the logistics of
      vaccine delivery must be taken into account. The addition of a suspension of
      killed Mycobacterium vaccae to BCG may increase its efficacy. Skin test data show
      that recognition of antigens common to all mycobacterial species and thought to
      be the first step in the protective immune response, is significantly enhanced by
      the additive. M. vaccae also contains a substance, or substances, "switching off"
      the tissue destructive aspect of the Koch phenomenon that is part of the
      immunopathology of tuberculosis. A suspension of killed M. vaccae alone can be
      used to enhance immune responses of persons unsuitable for BCG vaccination, such
      as those already tuberculin positive, and those with scars of earlier BCG
      vaccination.

PMID- 2001277
TI  - Isolation of a Salmonella-specific DNA hybridization probe.
AB  - A Salmonella-specific DNA fragment of the Salmonella typhimurium LT2 chromosome
      has been isolated. The fragment (2.3 kilobases (kb)) was used as a probe in a
      colony hybridization assay, where 185 strains of 93 different Salmonella serovars
      were correctly identified as belonging to Salmonella. The specificity of the
      probe was evaluated in colony hybridization assays on pure cultures of non
      Salmonella bacteria and on specimens with an indigenous flora. Sixty-three
      strains of 34 non-Salmonella Gram-negative species did not hybridize to the
      fragment. By DNA hybridization to faecal samples from calves, pigs and chickens,
      and samples of animal feed, three samples out of 10 positive by traditional
      culture methods gave negative results by hybridization, 45 samples were negative
      in both methods, while one sample was positive only in the hybridization assay.
      From this sample, Salmonella livingstone was isolated by a replica plate
      hybridization technique. The probe therefore proved 100% specific for the genus
      Salmonella. The 2.3 kb fragment may form the basis of hybridization assays for
      specific detection of Salmonella in food, environmental and clinical specimens.

PMID- 2001278
TI  - Alterations in human lung parenchyma after cytostatic therapy.
AB  - Chemotherapy does not only affect the viability of the tumor cell. It may also
      cause alterations in normal organs. Thus, tumor-free areas within human lung
      parenchyma of 63 surgical specimens of intrapulmonary metastases were analyzed to
      assess the extent of morphologic changes in response to previous cytostatic
      therapy. The material included 34 cases of sarcoma, 20 cases of germ cell tumors,
      6 cases of hypernephroid carcinoma, two cases of mammary carcinoma and one case
      of metastatic melanoma. All patients had received cytostatic therapy in generally
      applied regimens for more than two years. Morphologic analysis was carried out by
      routine procedures. In addition to conventional staining procedures including HE,
      PAS, and Sirius stain, further tools were employed to extend the array of
      determined characteristics. To evaluate any changes in the tissue in order to
      specifically recognized carbohydrate structures, labeled neoglycoproteins or
      proteoglycans with specificity for endogenous receptors that bind to mannose,
      maltose, L-fucose, lactose, N-acetyl-D-glucosamine, and heparin were used. A
      monoclonal antibody binding the HLA-DR receptor was also included in the study.
      As a control, sections of 20 cases with intrapulmonary metastases without
      exposure to previous cytostatic therapy were included. To address the further
      question whether cytostatic therapy may induces changes in tumor-free lung that
      show similarities to the organ in question, sections from 18 cases with
      tuberculosis and from 37 cases suffering from sarcoidosis were similarly
      examined. Focal interstitial fibrosis was seen in 28/63 (44%) of the patients
      receiving chemotherapy. In contrast, only 2/20 (10%) patients of the untreated
      group exhibited this alteration. An active fibrosis with proliferating smooth
      muscle cells was found in two cases, dysplastic pneumocytes in 10 cases (16%) in
      the group with cytostatic therapy, but in no cases in the untreated group.
      Expression of the HLA-DR receptor in the pneumocytes was observed in 27/63 cases
      (43%) of the cytostatic cohort, in 21/37 (57%) patients of the sarcoidosis
      cohort, in 15/18 (83%) patients of the tuberculosis cohort, and in 1/20 (5%) of
      the untreated patients. In contrast to sections from treated patients, binding of
      neoglycoproteins was low in the untreated cohort. Interestingly, similarities
      between the tuberculosis cohort and the cytostatic cohort were seen for receptors
      that are specific for fucose and lactose, respectively. The results suggest that
      long-lasting cytostatic therapy induces focal fibrosis in 40%-50% of the
      patients, mainly via unspecific interstitial inflammatory infiltrates. A
      hypersensitivity reaction or direct toxicity may less frequently lead to
      pathologic alterations.

PMID- 2001279
TI  - The juxtaglomerular apparatus of the spontaneously hypertensive rat.
AB  - Spontaneously hypertensive rats (SHR) are used to study the pathogenesis of
      essential hypertension. This study investigates the role of the renin-angiotensin
      system (RAS) in the pathogenesis of hypertension in SHRs and the morphometry of
      the JGA by a three-dimensional computer reconstruction program "GLOM" and
      electron microscopy. Systolic blood pressure (SBP) (tail cuff method) was higher
      in SHRs compared to controls (P less than 0.001). Plasma renin concentration
      (PRC) was lower in SHRs than in controls (P less than 0.001). Reconstruction of
      the JGA revealed granulated JG cells in the afferent and efferent arterioles and
      in the vascular tree away from the JGA area. Electron microscopy showed
      granulated JG cells in the afferent and efferent arterioles. The percentage
      volume of the granulated JG cells in SHR was significantly higher than in
      controls (P less than 0.01). A relationship was found between the percentage
      volume of granulated JG cells and the SBP in SHRs (r = 0.933, P less than 0.05).
      The wall/lumen perimeter ratio was also significantly higher in the SHRs compared
      to the controls (P less than 0.05). Low PRC in SHRs has been reported by several
      workers. The apparent hyperactivity of the JGA may indicate failure of renin
      release or an abnormal synthesis/secretion rate.

PMID- 2001280
TI  - A flow cytometric method to measure the stimulated mobilization and the
      intracellular pool of the adhesion promoting glucoprotein Mac-1.
AB  - The receptor for complement factor C3bi (Mac-1 or CR3) belongs to a complex of
      leukocyte surface glucoproteins (CD11/CD18) that are essential for chemotaxis and
      adhesion of human polymorphonuclear leukocytes (PMN). Granulocytes can increase
      their surface expression of Mac-1 upon stimulation and it is proposed that this
      depends on a rapid mobilization of an intracellular pool of Mac-1. In the present
      study we describe a cell membrane permeabilization method that enables the
      detection of the intracellular pool of Mac-1 in granulocytes by flow cytometry.
      The method is based on the use of the non-ionic detergent n-octyl-beta-D
      glucopyranoside (OG) to permeabilize the cell membranes of paraformaldehyde
      prefixed leukocytes. It is shown that fMLP (5 x 10(-7) M)-treated cells expose
      85% of the total detectable amount of Mac-1 molecules on the surfaces. The method
      makes it possible to measure the total detectable pool, the efficiency of Mac-1
      mobilization and the in vivo expression of the receptor. This could be of value
      when evaluating the role of adhesion proteins in the inflammatory response.

PMID- 2001281
TI  - Grouping of some clinically relevant gram-positive rods by automated fatty acid
      analysis. Diagnostic implications.
AB  - One hundred and ninety-four strains of aerobically growing Gram-positive rods of
      the genera Corynebacterium, Actinomyces, Arcanobacterium, Erysipelothrix,
      Listeria, Oerskovia, Nocardia, Rhodococcus, and of unnamed Center for Disease
      Control (CDC) groups were checked for cellular fatty acid profiles with the
      microbial Identification System (Microbial ID, Newark, Del., USA). In order to
      obtain unified data usable for the clinical laboratory, 24 or 48 h sheep blood
      agar cultures were used. It was thought that grouping and perhaps identification
      could be aided by this approach. With the aid of numerical analysis, four groups
      (two consisting of two subgroups each) were established. The discriminatory
      ability of the scheme, however, was only 77.2%, indicating that grouping of an
      unknown isolate could be done with some accuracy, but that speciation would still
      require biochemical testing.

PMID- 2001282
TI  - Identification and localization of a soluble antigen, Ag2, of 136 kDa from
      Plasmodium falciparum in vitro cultures.
AB  - The soluble antigens, antigen 2 (Ag2) and antigen 6 (Ag6), were copurified from
      supernatants of P. falciparum in vitro cultures by affinity chromatography and
      Fast Protein Liquid Chromatography. Rabbit antibodies to Ag2 were raised and
      characterized by crossed immunoelectrophoresis. Ag2 appeared as a duplet with
      molecular masses of 136 and 120 kDa when tested by immunoblotting.
      Immunoprecipitation experiments on Triton X-100 extracted antigens from
      synchronized cultures showed that the antigen was synthesized in the schizont
      stage. Ag2 was located near the surface of schizonts in the parasitophorous
      vacuole and in clefts in the infected erythrocyte cytoplasma as shown by
      immunogold electron microscopy.

PMID- 2001283
TI  - Bone marrow stroma in idiopathic myelofibrosis and other haematological diseases.
      An immunohistochemical study.
AB  - Bone marrow stroma was investigated immunohistochemically in 31 patients with
      haematological diseases, mainly idiopathic myelofibrosis (n = 8) and related
      chronic myeloproliferative disorders (n = 14). The bone marrow from patients with
      idiopathic myelofibrosis and some CML patients showed marked staining reactions
      with antibodies against type III procollagen (pN collagen), type IV collagen,
      fragment P1 of laminin and factor VIII. Patients with osteomyelosclerosis had
      particularly increased collagen content, including both newly deposited type III
      collagen (pN collagen) and mature collagen fibres. As in normal bone marrow,
      argyrophilic fibres and type III collagen displayed a close co-distribution,
      which was also demonstrated for type IV collagen and laminin. While normal bone
      marrow sinusoids had discontinuous basement membranes, fibrosing bone marrow was
      characterized by endothelial cell proliferation and capillarization, with the
      development of continuous sheets of basement membrane material beneath
      endothelial cells.

PMID- 2001284
TI  - Hepatitis D in Yaounde, Cameroon.
AB  - Although 10% of the Yaounde population are hepatitis B surface antigen (HBsAg)
      positive, nothing is known about hepatitis D virus (HDV) infection in them. Sera
      from 110 HBsAg subjects were tested for HDV infection (antibody and antigen). The
      subjects were 43 pregnant women, 23 prostitutes, 20 patients with febrile
      jaundice, 16 multitransfused sickle cell children and 8 medical students. Thirty
      of the 110 (27.3%) had antibodies to the HDV (HDV-Ab). Two of 91 tested for HDV
      antigen (2.2%) were positive. The highest HDV-Ab prevalence (62.5%) was obtained
      from sickle cell children (10/16). Thus, HDV infection was found in about one
      fifth to one third of the HBsAg-positive subjects we studied and the main route
      of transmission appears to be by blood transfusion.

PMID- 2001285
TI  - Delineation of olfactory pathways in the frog nervous system by unique
      glycoconjugates and N-CAM glycoforms.
AB  - The olfactory neuroepithelium, which contains the primary sensory olfactory
      neurons, continually undergoes neurogenesis and axonal outgrowth throughout life.
      We describe here several new olfactory system-specific glycoforms of the neural
      cell adhesion molecule N-CAM in the frog, R. catesbeiana. Using immunochemical
      methods for in situ localization, we show that the lectin dolichos biflorus
      agglutinin (DBA) and two monoclonal antibodies, 9OE and 3A6, detect three unique
      N-CAM forms present on primary sensory olfactory axons. In addition, DBA and
      monoclonal antibody 9OE recognize glycoconjugates and/or N-CAM glycoforms
      expressed specifically in discrete central olfactory pathways and regions in frog
      brain. This is a novel example of unique adhesion molecule forms present in a
      chain of two neurons within a vertebrate neural pathway. Together these
      glycoconjugates and N-CAM glycoforms may participate in cellular interactions
      associated with olfactory system pathway formation and renewal.

PMID- 2001286
TI  - Distribution of mRNA for the calmodulin-sensitive adenylate cyclase in rat brain:
      expression in areas associated with learning and memory.
AB  - The Drosophila learning mutant, rutabaga, is deficient in the calmodulin
      sensitive adenylate cyclase, and studies of associative learning in Aplysia have
      implicated this enzyme in neuroplasticity. Therefore, the distribution of mRNA
      encoding the calmodulin-sensitive adenylate cyclase in rat brain was examined by
      in situ hybridization. mRNA for this enzyme is expressed in specific areas of
      brain that have been implicated in learning and memory, including the neocortex,
      the hippocampus, and the olfactory system. The presence of mRNA for this enzyme
      in the pyramidal and granule cells of the hippocampal formation provides evidence
      that it is found in neurons. These data are consistent with the proposal that the
      calmodulin-sensitive adenylate cyclase plays an important role in learning and
      memory.

PMID- 2001287
TI  - Novel potassium channels encoded by the Shaker locus in Drosophila
      photoreceptors.
AB  - The Shaker gene, responsible for A-type potassium channels in Drosophila muscle,
      encodes a large family of transcripts capable of generating a variety of
      kinetically distinct A channels when expressed in oocytes. We describe a distinct
      class of A channel encoded by the Shaker gene in a novel preparation of
      dissociated Drosophila photoreceptors. Whole-cell recordings reveal a rapidly
      inactivating A current that is absent in Shaker mutants and that can be readily
      isolated in cell-attached patches. Although very similar to their muscle
      counterparts, the photoreceptor A channels show a striking 40-50 mV negative
      shift in their voltage-operating range. Two mutations (ShE62 and T(1;Y)W32),
      which exclude only certain classes of Shaker transcripts, were used to show that
      photoreceptor A channels are encoded by multiple transcripts distinct from those
      encoding muscle A channels, while PCR techniques identified four transcripts
      (ShA1, ShA2, ShG1, and ShG2) in mRNA from dissected retina.

PMID- 2001288
TI  - Endothelial and epithelial cell adhesion molecules.
AB  - This review will discuss a number of specific cell adhesion molecules present on
      the surface of endothelial and epithelial cells in the lung. Molecules such as
      integrins, proteoglycans, and the hyaluronic acid receptor, CD44, are found on
      the abluminal or basement membrane side of the cell and function as cell
      substratum receptors. Cadherins, integrins, and platelet-endothelial cell
      adhesion molecule-1 (PECAM-1) are present at the cell-cell borders of adjacent
      endothelial and/or epithelial cells and function to initiate or maintain cell
      cell adhesion. Finally, a number of inducible cell adhesion molecules such as
      endothelial-leukocyte adhesion molecule-1 (ELAM-1), granule-associated membrane
      protein 140 (GMP140), intercellular adhesion molecule-1 (ICAM-1), and vascular
      cell adhesion molecule-1 (VCAM-1) are expressed on the luminal surfaces of these
      cells during inflammation and function as cell-cell adhesion molecules important
      in white blood cell, platelet, or tumor cell adhesion. These adhesion molecules
      likely play important roles in maintaining the normal structure and function of
      the lung, as well as participating in pulmonary processes such as inflammation,
      wound healing, and the development and spread of malignant disease.

PMID- 2001289
TI  - Difference in effect of inhibitors of energy metabolism on endothelium-dependent
      relaxation of rat pulmonary artery and aorta.
AB  - Previous studies have suggested that systemic artery endothelial cell production
      of the nitrovasodilator endothelium-derived relaxing factor (EDRF) is dependent
      upon oxidative energy production. This study was undertaken to test if pulmonary
      artery (PA) EDRF has a similar requirement for oxidative phosphorylation. The
      effects of inhibitors of oxidative phosphorylation and glycolysis on endothelium
      dependent relaxation were studied in rat aortic and PA rings. In aortic rings,
      0.1 microM rotenone and 0.1 microM antimycin A, and, to a lesser extent, 50 mM 2
      deoxyglucose, inhibited endothelium-dependent relaxation to acetylcholine and
      adenosine diphosphate. Relaxation to the receptor-independent calcium ionophore
      A23187 was less severely affected, and relaxation to the direct smooth muscle
      dilator sodium nitroprusside was unaffected. The inhibitors had much less effect
      on PA relaxation, decreasing the potency but not the efficacy of the endothelium
      dependent dilators. These results suggest that the dependence on oxidative energy
      production for endothelium-dependent relaxation may differ between the systemic
      and pulmonary vascular beds, and that in pulmonary arterial endothelium,
      oxidative energy production may not be required for receptor-mediated production
      and/or release of EDRF. The resistance of PA endothelium to decreases in
      oxidative energy production may contribute to the normally low tone maintained in
      this circuit in vivo.

PMID- 2001290
TI  - Tetrodotoxin does not block the epithelium-dependent release of prostaglandin E2
      induced by electrical field stimulation in isolated ferret trachea.
AB  - Electrical field stimulation (EFS) has previously been shown to induce the
      release of prostaglandin (PG) E2 from ferret tracheal epithelium. We have now
      conducted a study to see whether this effect of EFS is due to the activation of
      nerves or whether it is a non-neural effect. The release of PGE2 and 6-keto-PGF1
      alpha into the bath fluid was assayed in isolated ferret tracheas with (E+) or
      without (E-) epithelium, stimulated by either EFS or direct vagal nerve
      stimulation (DNS) repeatedly for 120 min. EFS-stimulated E+ preparations showed a
      gradual decline in the contractile responses (30 +/- 1% of baseline) and an
      increase in PGE2 to 296 +/- 38 pg/ml. In EFS-stimulated, epithelium-denuded (E-)
      preparations, the decline was significantly lower (11 +/- 5%), as well as the
      final concentration of PGE2 (107 +/- 21 pg/ml). In DNS-stimulated E+
      preparations, the contraction decline was 8 +/- 1% and the final concentration of
      PGE2 was less than 6 pg/ml. Although tetrodotoxin (TTX) abolished the contractile
      response in EFS-stimulated E+ preparations, it did not significantly reduce the
      release of PGE2 (260 +/- 6 pg/ml), whereas atropine partly counteracted the
      release. The bath concentration of 6-keto-PGF1 alpha increased, independently of
      the electrical stimulation, contractile response, or presence of the epithelium.
      We conclude that EFS activates the epithelium-dependent release of PGE2 by a TTX
      resistant mechanism. This may be due to an activation of TTX-resistant nerves, or
      possibly to a non-neural effect, such as a direct effect on the epithelial cells.
      The results indicate that the airway epithelium has the ability to respond to
      certain stimuli with a pronounced release of PGE2, thereby counteracting
      bronchoconstriction.

PMID- 2001291
TI  - Molecular structure of a functional rat gene for manganese-containing superoxide
      dismutase.
AB  - The manganese-containing superoxide dismutase (MnSOD) constitutes one of the
      major cellular defense mechanisms against the toxic effects of superoxide
      radical. The development of tolerance in adult rats to lethal exposure of O2
      (100%) after pre-exposing them to a sublethal concentration of O2 (85%) was found
      to be closely associated with the increased activity of this enzyme in the lungs.
      Further experiments have shown that the transcriptional rate of the gene coding
      for MnSOD in rat lungs is increased at day 3 of 85% O2 exposure. To elucidate the
      nature of this transcriptional activation during hyperoxic insults, we chose to
      first understand the structure of the rat MnSOD gene. Three overlapping rat
      genomic fragments were isolated, and the DNA sequence containing the whole MnSOD
      gene was completely determined. The rat MnSOD gene contains at least five exons
      and is located in one piece of 16.4-kb EcoRI genomic DNA fragment. However,
      Southern blot analysis of total rat genomic DNA probed with MnSOD cDNA revealed
      an additional hybridizing 8.6-kb EcoRI genomic fragment besides the 16.4-kb one.
      To clarify the origin of this unexpected hybridizing genomic fragment, three
      unique genomic sequences derived from the promoter, intron 2, and the 3'
      untranslated region of the genomic clones were used to rehybridize the same
      Southern blot filter and were found to only hybridize to the 16.4-kb but not 8.5
      kb EcoRI genomic fragment. These data suggest: (1) two MnSOD genes are present
      per haploid rat genome, and (2) all three cloned genomic fragments are derived
      from the MnSOD gene, which is located in the 16.4-kb EcoRI genomic
      fragment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2001292
TI  - Requirement for cell-to-cell contact for the immunosuppressive activity of human
      alveolar macrophages.
AB  - The ability of alveolar macrophages (AM) obtained by bronchoalveolar lavage of
      healthy volunteers to suppress T lymphocyte responses to the mitogen
      phytohemagglutinin (PHA) in vitro was investigated. AM but not monocytes (MN)
      inhibited responses of peripheral blood mononuclear cells (PBMC) to PHA as
      measured by incorporation of [3H]thymidine [( 3H]TdR) and interleukin-2 (IL-2)
      expression. Supernatants of AM generated for various periods and with various
      concentrations of cells did not, however, inhibit PBMC responses to PHA. To
      examine the role of cell contact in the inhibitory activity of AM, AM or MN were
      added to PBMC in 6-well plates either directly (in co-culture) or separated by a
      0.45-micron filter. MN did not inhibit PBMC blastogenic responses under either
      condition. AM at a 1:2 ratio with PBMC inhibited blastogenesis by 75 +/- 11%
      (mean +/- SD, n = 3, P less than 0.01) when cultured directly with PBMC but had
      no inhibitory effect on blastogenesis when physically separated from target PBMC.
      AM in co-culture with PBMC also inhibited PHA-stimulated IL-2 production by 70%
      but did not inhibit IL-2 production when AM were separated from PBMC in dual
      chambers. To assess the role of the cell surface in the inhibitory activity of
      AM, AM and MN were fixed with 2% paraformaldehyde. Neither fixed nor unfixed MN
      inhibited PBMC blastogenic responses, but both fixed and unfixed AM inhibited
      responses similarly (77 to 95%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2001293
TI  - Cancer in Greenland 1953-1985.

PMID- 2001294
TI  - Orange solvent and hydrogen peroxide in endodontics.

PMID- 2001295
TI  - Oral cancer: a comparative study between 1962-67 and 1980-84 in England and
      Wales.
AB  - This study reveals that changes are occurring in the pattern of oral cancer.
      Despite decreases in the number of lip and salivary gland cases, intra-oral
      cancer is increasing. The number of new cases is rising, especially in females,
      and it is presenting at a younger age in males. Intra-oral cancer deaths have
      increased, with females showing a 40% rise. The mortality rate has deteriorated
      to 62%. It is possible that these increases could be attributed to continued lack
      of public awareness of the disease and a considerable rise in alcohol consumption
      per head of population in the UK.

PMID- 2001296
TI  - Ocular injury and infection in dental practice. A survey and a review of the
      literature.
AB  - Dental surgeons, dental surgery assistants and patients are at risk of eye injury
      during certain dental procedures. We have reviewed the literature to reemphasise
      these hazards and have conducted a survey to determine how often injuries occur
      and what measures are taken to prevent them.

PMID- 2001297
TI  - Liquid gallium alloys for metallic plastic fillings.
AB  - Ga-In-Sn alloys that are liquid at room temperature have been developed to
      replace mercury in metal plastic fillings. These liquid alloys were mixed with Ag
      Pd-Sn-Cu-Zn to form powder alloys, 'a plasto-metallic body'. Various physical
      properties of these materials were evaluated. Strength increased markedly
      immediately after mixing, and polishing was possible on the same day. A good
      marginal seal could be expected as these materials expand on setting. The
      technique for filling is simpler and more rapid than is the case with amalgam
      materials. These materials also seem to be useful in paediatric dentistry for the
      handicapped, where extensive treatments are frequently performed under general
      anaesthesia.

PMID- 2001298
TI  - The Wilfred Fish memorial lecture. The Hunterian tradition in dentistry.
AB  - The influence of William and John Hunter upon the development of Medicine and
      Dentistry in Britain has endured for more than two centuries. John Hunter's first
      book set out the morphological details of the teeth and their associated
      structures. From this basis he sought to attain an understanding of physiological
      and pathological processes by studies of the entire animal kingdom and by
      experimentation. His foundations of scientific dentistry were built upon by John
      Tomes and Wilfred Fish in subsequent centuries, both invoking the use of
      microscopy to enhance Hunter's naked eye descriptions and to interpret the
      results of experiments. Both, too, are inseparably linked with the history of the
      Royal College of Surgeons of England by the parts they played in establishing and
      preserving the place of their profession in that great repository of Hunter's
      teachings.

PMID- 2001299
TI  - Quality control in orthodontics: risk/benefit considerations.
AB  - The literature concerning risk/benefit appraisal for orthodontic treatment is
      reviewed with respect to factors which influence dental health, social
      psychological well-being and the harmful effects of orthodontic treatment. There
      is little evidence to suggest that the absence of malocclusion is associated with
      a measurably higher self-esteem and life fulfillment, or with major advantages
      for dental health, except for a limited number of traits. With regard to
      treatment, small risks of iatrogenic harm exist, while the effects of partial or
      total failure of treatment, and the lack of long-term stability of results should
      not be underestimated.

PMID- 2001300
TI  - Referral of child patients from the Community Dental Service to the General
      Dental Service: one year's experience.
AB  - The Community Dental Service has been encouraged to refer regular attending
      patients to General Dental Practice whilst maintaining a monitoring system to
      ensure that referred patients do not 'fall through the net'. The referral and
      monitoring system run by Halton Health Authority for one year is described.
      During this period 112 motivated patients were identified as being suitable for
      referral to general practice. Of these, 85 agreed to referral and 27 refused. Of
      those referred, 69 subsequently attended but 16 failed to attend and 14 of these
      did not respond to a further recall by the CDS. Far from acting as a safety net
      service the CDS may, in pursuing this referral policy, be actually increasing the
      number of irregular attenders in some localities and for this reason Halton is
      reviewing the speed with which the referral policy is being implemented.

PMID- 2001301
TI  - Hungary: a change from decay.
AB  - At the end of October a group of dentists departed for Hungary. They arrived
      without mishap--then came the difficult part, getting to their hotel. Once this
      had been overcome, the group enjoyed an informative and entertaining Study Tour,
      learning about the state of dentistry in the country, as well as sampling its
      more obvious attractions. Donald Timms, a member of the group reports.

PMID- 2001302
TI  - Vocational training. The interview.
AB  - January: the beginning of another year and time for another batch of dental
      graduates to decide on their next move. For those considering entering a
      vocational training scheme, Len D'Cruz outlines what a prospective trainee might
      expect at the interview stage and, in subsequent articles, during that dreaded
      first day and on the day releases.

PMID- 2001303
TI  - Dental software problems.

PMID- 2001304
TI  - Dental surgery assistants' pay: the 1989 BDA survey.

PMID- 2001305
TI  - LDC funding: British Dental Guild Claims.

PMID- 2001306
TI  - Representative board.

PMID- 2001307
TI  - 'The Yankee dodge'.

PMID- 2001309
TI  - Reprieve for dental general anaesthesia.

PMID- 2001308
TI  - Catch 22.

PMID- 2001310
TI  - Dental College 'inevitable'.

PMID- 2001311
TI  - 'Resistance to analgesia: report of a case treated using 5 per cent lignocaine'.

PMID- 2001312
TI  - Five-year survival improves in cancers of the lip.

PMID- 2001313
TI  - 'All is not well'.

PMID- 2001314
TI  - Report on LDC conference 'rubbishes everything'.

PMID- 2001315
TI  - A comparison of two splints in the treatment of TMJ pain dysfunction syndrome.
      Can occlusal analysis be used to predict success of splint therapy?
AB  - Controversy surrounds the diagnosis and treatment of TMJ pain dysfunction
      syndrome (TMJPDS). This is also reflected in the widely divergent recommendations
      in splint design. A study was undertaken to examine the comparative success rates
      of treatment by two occlusal splints with apparently diametrically opposed modes
      of action and to determine whether there were any factors which could be utilised
      to predict the success of splint therapy. Sixty-eight TMJPDS patients were
      randomly distributed into one of two comparable groups and were treated solely
      with an occlusal splint for night time wear. One group was treated with a
      stabilisation splint (SS) and the other with a localised occlusal interference
      splint (LOIS). The success rate at review with the SS was 67.6% and with the LOIS
      was 80.9%. This difference was not statistically significant. Pretreatment
      occlusal analysis demonstrated three indicators of successful splint therapy
      which appeared to be independent of design. These were the absence of centric
      relation occlusion, the existence of non-working side interferences and an
      absence of ideal anterior guidance.

PMID- 2001316
TI  - Reducing failure rates for in-patient oral surgery. The use of a pre-admission
      clinic.
AB  - A large proportion of oral and maxillofacial surgery operations are non-urgent,
      elective procedures. Approximately 30% of patients called for operation from
      routine waiting lists consistently fail to attend, thus leading to inefficient
      bed utilisation and wastage of theatre time. In an attempt to reduce patient
      failure rates and to investigate reasons for non-attendance, the Department of
      Oral and Maxillofacial Surgery developed a new pre-admission clinic; admission
      dates for in-patient surgery are only arranged following successful attendance
      and satisfactory 'clerking in' at the pre-admission clinic. Over an initial 5
      month period, in-patient attendance rates increased to 87% and, at the same time,
      validation of waiting lists was facilitated, with nearly three-quarters of clinic
      non-attenders eventually being removed from the lists. The pre-admission clinic
      thus appears to offer a useful and versatile approach towards more efficient in
      patient management.

PMID- 2001317
TI  - Surgical management of trigeminal neuralgia.
AB  - Severe pain which cannot be controlled medically is the major factor for which
      patients seek surgical treatment for trigeminal neuralgia. Patients should be
      neurologically screened and have an enhanced CT scan prior to surgery in order to
      exclude a secondary cause for the disease. Peripheral techniques such as
      cryotherapy and alcohol injections give short-term pain relief but have few
      complications. The most popular operation, radiofrequency thermocoagulation in
      the Gasserian ganglion, has a mean recurrence of 3 years, but leaves patients
      with extensive sensory loss. Microvascular decompression and partial rhizotomy
      are major neurosurgical procedures that have a low recurrence rate but carry a
      risk of death and serious morbidity. Patients should be more involved in the
      choice of surgery.

PMID- 2001318
TI  - Two cases of oral infection by methicillin-resistant Staphylococcus aureus.
AB  - Two cases of oral infection with multi-resistant Staphylococcus aureus (MRSA) are
      described who were found to carry the same MRSA. Both cases were managed without
      the use of antibiotics. The practitioner was found not to have worn gloves
      routinely and this may have been the source of the MRSA.

PMID- 2001319
TI  - The happy puppet syndrome--dentofacial manifestations.
AB  - Two cases of 'happy puppet' syndrome are presented, with descriptions of salient
      clinical features, especially the dentofacial anomalies. Potential management
      problems are discussed.

PMID- 2001320
TI  - Quality control in orthodontics: factors influencing the receipt of orthodontic
      treatment.
AB  - The factors which influence the uptake of orthodontic treatment are reviewed with
      respect to the features and aspirations of the consumers (patients and parents)
      and the providers (dentists, orthodontists and health system). It appears that
      the assessment of orthodontic treatment need is influenced by many variables
      relating to opportunity and demand for treatment; this results in a marked lack
      of uniformity in treatment uptake.

PMID- 2001321
TI  - The British Association of Orthodontists--what do the next 25 years hold?

PMID- 2001322
TI  - An observation of the dental department and the treatment needs of patients
      presenting at Dohnavur Hospital, southern India.
AB  - A hope and a prayer, and a healthy measure of innovative inspiration, makes
      Dohnavur a surprisingly archaic, but reassuringly effective hospital, despite the
      appalling shortage of funds and equipment. Rebekah Anderson and Helen Fuller
      spent the month of their student elective in southern India and here reveal some
      of the dental anachronisms they encountered.

PMID- 2001323
TI  - Updating practices among Yorkshire general dental practitioners.
AB  - Ninety-eight per cent was the response achieved by a June 1989 postal survey to
      determine how general dental practitioners (GDPs) in Yorkshire Region maintain
      their professional knowledge. Such a good response adds confidence to the
      survey's findings which show many GDPs are educationally active and use a variety
      of media to keep up to date. Nevertheless, there remains a substantial proportion
      who should be doing more and need encouragement.

PMID- 2001324
TI  - Continuing education in the GDS. An England survey.
AB  - The Department of Health's Management Consultancy Unit Survey of Postgraduate
      Dental Training in the General Dental Service surveyed a statistically valid
      sample of general dental practitioners (GDPs) in England to determine the rate of
      attendance at formal training courses, to look at the needs and expectations of
      practitioners and to identify factors influencing non-attendance. The results
      indicate that 79% of GDPs attended some form of training during 1989. Seventy-one
      per cent of the non-attenders who received Section 63 video programmes watched
      all the videos they received. Non-attendance rates were highest in those aged
      under 30 or over 50 years. Ninety-three per cent of practitioners felt their
      needs were met to an acceptable level and 52% rated their needs very well met or
      well met.

PMID- 2001325
TI  - Nurse executive advancement: being on the cutting edge.

PMID- 2001326
TI  - The challenge of contracting with consultants.

PMID- 2001327
TI  - Ready or not: accepting changes in health care.

PMID- 2001328
TI  - Nursing at the far reaches of society: challenges and opportunities.

PMID- 2001329
TI  - Binding of [26-3H]-epi-bryostatin 4 to protein kinase C.
AB  - Structure activity analysis of protein kinase C modulators may permit design of
      selective inhibitors of this important regulatory enzyme. Modeling suggests that
      the C-26 secondary hydroxyl of bryostatin is homologous to the C-20 primary
      hydroxyl of phorbol or the C-3 primary hydroxyl of sn-1,2-diacylglycerols
      (Wender, P. A.; Cribbs, C. M.; Koehler, K. F.; Sharkey, N. A.; Herald, C. L.;
      Kamano, Y.; Pettit, G. R.; Blumberg, P. M. Modeling of the bryostatins to the
      phorbol ester pharmacophore on protein kinase C. Proc. Natl. Acad. Sci. USA
      85:7197-7201; 1980). We have characterized the binding activity to protein kinase
      C of the epimer of bryostatin 4 with the configuration at C-26 inverted from R
      (natural configuration) to S. The Kd of [26-3H]-epi-bryostatin 4 for protein
      kinase C reconstituted in the presence of phosphatidylserine was 13 +/- 2 nM. [26
      3H]-Epi-bryostatin 4 thus retained moderate absolute affinity. Relatively,
      however, inversion at the chiral center at C-26 caused a dramatic decrease in
      binding affinity. Binding of [26-3H]-epi-bryostatin 4 was competitively inhibited
      by phorbol 12,13-diacetate, as expected for ligands that interact at the same
      binding site.

PMID- 2001330
TI  - The role of the phorbol ester receptor/protein kinase C in the sensitivity of
      leukemic cells to anthracyclines.
AB  - The phorbol ester receptor (PER), which is believed to be identical to protein
      kinase C (PKC), has been implicated in the control of the sensitivities of tumor
      cells to certain forms of cancer chemotherapy. We evaluated the effects of
      regulating the expression of PER/PKC on the sensitivity of the R1B6 subclone of
      HL-60 human promyelocytic leukemic cells to anthracyclines. This cell line is
      resistant to the effects of phorbol esters on cellular differentiation by virtue
      of a down-regulated PER. R1B6 cells were maintained in phorbol 12, 13 dibutyric
      acid (PDBu). Twenty four to thirty six hours after removal of PDBu from the
      medium there was a 3-fold increase in the number of receptors compared to
      baseline values measured by [3H]-PDBu binding and a marked increase in the
      activity of PKC as measured by calcium-phospholipid dependent incorporation of
      [32P] into histone. Despite these changes in the number of PER and in the
      activity of PKC there was no difference in the cellular accumulation of [3H]
      daunomycin or in the sensitivity of cells to the toxic effects of doxorubicin.
      Furthermore, there was no difference between the R1B6 cells and the parental HL
      60 line in their intrinsic sensitivities to doxorubicin. These studies
      demonstrate that alterations in the expression of PER and the activity of PKC
      alone are not sufficient to influence anthracycline accumulation or toxicity in
      R1B6 human leukemic cells in contrast to recently reported results using other
      cell lines.

PMID- 2001331
TI  - Characterization of binding proteins from ovarian carcinoma and kidney tubule
      cells that are specific for cisplatin modified DNA.
AB  - We have detected proteins in nuclear extracts from ovarian carcinoma cells and
      kidney tubule cells that bind specifically to platinated DNA. A 123-bp
      restriction fragment was platinated with cisplatin (DDP) to a formal molar
      platinum to nucleotide ratio of 0.05 and end-labeled with [32P]-dCTP. Incubation
      with nuclear extracts from 2008 human ovarian carcinoma cells caused shifts in
      the mobility of this probe in non-denaturing polyacrylamide gels. Proteinase K,
      but not ribonuclease A, destroyed the bands. Comparison of the shifted bands
      generated by DDP-resistant 2008 and A2780 human ovarian carcinoma cell nuclear
      extracts with bands from the corresponding sensitive cells showed no differences
      in protein levels. The affinity of the proteins for the probe was the same in
      sensitive and resistant 2008 nuclear extracts as determined by competition with
      platinated salmon sperm DNA. These proteins also bound to a probe damaged with
      1,2-diaminocyclohexaneplatinum(II) dichloride but did not bind to a trans-DDP
      platinated probe. No differences were found in the levels of UV4 or UV5 Chinese
      hamster ovary cells, which were hypersensitive to DDP compared to wild-type AA8
      cells. MDCK and LLC-PK1 kidney tubule cells, which were more resistant to DDP
      cytotoxicity than 2008 cells, exhibited decreased levels of these proteins. We
      conclude that, although these proteins that recognize DDP damage in DNA may be
      involved in excision repair, their levels did not correlate with DDP sensitivity
      in this panel of cell lines.

PMID- 2001332
TI  - Morphometry of bladder carcinoma: morphometry and grading complement each other.
AB  - Subjective grading of bladder carcinoma is a good predictor of the clinical
      outcome in those patients whose tumours are grade 1 or grade 3. However, in grade
      2 tumours, which account for 45% of cases, grading has little predictive value in
      an individual patient. We have complemented the use of subjective grading with
      measurement of nuclear area and used a calculation of the distribution of nuclear
      sizes as a predictor of the clinical course. When subjective grading was
      complemented by morphometry the outcome was correctly predicted in 55 of 58 cases
      and all cases with poor clinical outcome were identified.

PMID- 2001333
TI  - The significance of morphometric methods in cytologic diagnostics:
      differentiation between mesothelial cells, mesothelioma cells and metastatic
      adenocarcinoma cells in pleural effusions with special emphasis on chromatin
      texture.
AB  - Opinions differ widely as to the value of morphometric techniques for
      differentiating between mesothelial cells, mesothelioma cells and metastatic
      adenocarcinoma cells in pleural effusions. The significance of the changes in the
      chromatin structure to differentiate between these three cell types was stressed
      by various scientific groups only qualitatively, and until now no group has used
      digital methods to quantify chromatin structures. The controversy about the value
      of morphometric methods was the reason for conducting the following study. We
      wanted to investigate (i) the importance of various planimetric and texture
      parameters as well as invariant moments as morphometric discriminators; and (ii)
      to set up a data structure to make possible the further diagnostic use of the
      multivariate morphometric analyses method for other applications. The present
      findings show that nuclear size and form are not the decisive factors in
      differentiating between reactive cells and mesothelioma cells, but pixel related
      texture parameters and invariant moments are. All parameter types used showed
      differences between reactive cells and cells of adenocarcinoma metastases.
      Invariant moments and shape descriptors, but not texture parameters are used to
      discriminate between mesothelioma cells and cells of adenocarcinoma metastases.

PMID- 2001334
TI  - Quantitative evaluation of the tumour-stroma border by exponential regression
      analysis.
AB  - The architecture of the tumour margin is an essential feature for the
      histological diagnosis of certain neoplasms. In a previous study we have shown by
      computer simulations, that the degree of tumour cell motility and proliferation
      influences qualitative morphological criteria of the tumour border. Here we
      propose a method for an objective, quantitative description of the tumour cell
      distribution at the tumour-stroma border. 100 morphological patterns generated by
      computer simulation with different preset degrees of motility and proliferation
      were evaluated. On a measuring path starting at the most peripheral cell and
      going towards the tumour centre, the density of tumour cells for each distance
      from the tumour margin was calculated from the number of cells within a 5 x 5
      matrix around each measuring point. An exponential regression function was
      adapted to the measured density distribution. The parameters of the regression
      curve and 'the goodness of fit' were tested for correlation with the preset
      simulation parameters. It was found that the degree of motility and proliferation
      can be deduced from the quantitative descriptors of the tumour margin (linear
      regression of the preset values and of the values estimated from the
      morphological analysis: r = 0.903; t = 20.7; P less than 0.001). Besides the
      evaluation of computer-simulated morphological patterns, the same measuring
      procedure can also be applied to histological slides of melanocytic skin tumours
      using automated image analysis.

PMID- 2001335
TI  - Imaging of fluorescing microscopic objects.

PMID- 2001336
TI  - Looking forward in oncology.

PMID- 2001337
TI  - Assessing quality of life in patients treated for advanced head and neck cancer.
AB  - A pilot study was undertaken to determine which measures of Quality of Life (QL)
      would be of most use in the follow-up of patients participating in clinical
      trials of treatments for head and neck cancer. A total of 96 non-randomized
      patients who had been treated for head and neck cancer either by surgery (three
      patients), radiotherapy (54 patients), or combined modality therapy (39 patients)
      completed a detailed questionnaire assessing a wide range of QL parameters. All
      participating patients were clinically disease-free. It was found that questions
      relating to quality of speech, ability to eat, levels of energy and activity, and
      aspects of psychological wellbeing detected the largest effects on QL. The level
      of QL impairment was consistently greater in those patients treated by surgery
      plus radiotherapy as compared to those treated by radiotherapy alone. Eleven
      patients were interviewed in their own homes and the findings generally supported
      the conclusions drawn from the questionnaire responses. The interviews also
      demonstrated that impairment of arm movement amongst some surgically treated
      patients detracted from QL by causing difficulties in performing everyday
      selfcare and domestic tasks. This study has provided the basis for a QL
      assessment to be incorporated into a randomized trial of radiotherapy alone
      versus surgery plus radiotherapy in the treatment of advanced head and neck
      cancer. The findings suggest that QL impairment is greater for patients who have
      surgery in addition to radiotherapy as primary treatment but this may be
      acceptable if a clear survival advantage is demonstrated.

PMID- 2001338
TI  - The sensitivity of human tissues to changes in dose fractionation: deductions
      from the RCR survey among UK radiotherapists.
AB  - The dosage prescriptions reported in the Royal College of Radiologists'
      fractionation survey among radiotherapists have been further analysed using model
      equations in order to deduce estimates of fractionation-sensitivity parameters
      for each of the six cases under consideration. For example, using the linear
      quadratic model, including a (significant) time factor, with radical treatments
      of a T2 breast carcinoma or a T1N0 squamous carcinoma of the vocal cord, the
      (alpha/beta) ratios were 26 +/- 20 Gy and 37 +/- 46 Gy, respectively. The values
      of the time factor, expressed as the maximum extra dose required per day to
      counteract the decrease in effect with increasing overall time (gamma/alpha),
      were 0.60 and 0.45 Gy/day respectively. Using the Ellis formula, which provided a
      significantly better fit to the dosage prescription (P = 0.003), the exponents of
      N were calculated to be 0.24 +/- 0.05 and 0.27 +/- 0.07, respectively. The
      corresponding values of the T exponent were 0.16 +/- 0.06 and 0.014 +/- 0.075.
      About 20% of radiotherapists prescribed doses greater than +/- 10% from the mean
      fitted values for the breast treatment, and about 6% of them in the case of the
      vocal cord.

PMID- 2001339
TI  - The value of follow-up in stage II carcinoma of the cervix.
AB  - The optimal frequency of clinic follow-up after radical radiotherapy to early
      cervical cancer is not well established. A retrospective analysis was carried out
      of 392 patients with FIGO Stage IIA and IIB carcinoma of the cervix treated by
      radical radiotherapy who attended a radiotherapy clinic for follow-up. A total of
      38 (43%) of the 87 locoregional and 25 (38%) of the 66 metastatic relapses were
      detected at routine clinic visits. There were 72 clinic visits per relapse
      detected. The majority of locoregional and metastatic relapses whether detected
      at routine or interval visits were symptomatic of the locoregional recurrences
      78% (42/54) occurred in the first two years following treatment. The majority
      were advanced. 7% (4/54) of locoregional relapses occurred after 5 years. Only
      17% (9/54) of patients with locoregional relapse underwent salvage surgery. More
      intensive follow-up in the first two years is recommended.

PMID- 2001340
TI  - Prechemotherapy serum CA125 level as a predictor of survival outcome in
      epithelial carcinoma of the ovary.
AB  - A total of 55 patients with epithelial ovarian carcinoma treated with platinum
      based chemotherapy were followed for a minimum period of 2 years. Of these 22
      patients had a prechemotherapy serum CA125 level of less than 50 ku/l and 33
      patients had a serum CA125 level of greater than or equal to 50 ku/l. The 5-year
      actuarial survival of the two groups were 75% and 10% respectively.
      Prechemotherapy CA125 level taken 4 weeks after debulking surgery may predict the
      eventual survival outcome in epithelial ovarian cancer patients who undergo
      chemotherapy treatment.

PMID- 2001341
TI  - Clinical oncology services to district general hospitals: report of a working
      party of the Royal College of Radiologists.
AB  - We conducted a survey of multidisciplinary non-surgical cancer services in
      district general hospitals without departments of radiotherapy and oncology. All
      consultants in clinical oncology (radiotherapy and oncology) in the United
      Kingdom were sent a questionnaire. This report is based on the analysis of
      information on 235 district general hospitals, which have an average of 450 acute
      or general beds. Non-surgical medical care for cancer patients at these hospitals
      is mainly provided by consultants in clinical oncology based at cancer centres.
      Initial assessment and follow-up, and some investigations and drug treatment, are
      organized at the district general hospitals, but radiotherapy and a substantial
      proportion of cytotoxic chemotherapy is administered at the cancer centres. The
      principal finding of the survey is that the average total weekly commitment of
      consultants in clinical oncology at district general hospitals is just under two
      sessions. We estimate that for each session at present provided at these
      hospitals there are five new cancer patients who would benefit from a specialized
      oncological opinion. For each new patient consultation there is a need for 5-10
      times as many follow-up consultations. It is clear that the time available for
      cancer patients at district general hospitals, which on average are 22 miles away
      from the cancer centres, is far from adequate. We believe that it is correct to
      continue to base cancer services at cancer centres. This helps to ensure the
      maintenance of high standards and continuity of care. There is no need to alter
      the system, but there is a need to increase substantially specialist oncological
      presence at district general hospitals through the appointment of additional
      visiting consultants.

PMID- 2001342
TI  - A case of spontaneous regression of metastatic testicular teratoma.
AB  - We report the apparently spontaneous regression of metastatic disease in a young
      man who had previously undergone orchidectomy for a primary testicular teratoma.
      Serial serum tumour marker estimations revealed a sharp rise followed by a
      spontaneous decline in levels in a patient who had requested that chemotherapy be
      deferred for personal reasons.

PMID- 2001343
TI  - Osteomyelitis of the rib presenting as an apical lung cancer.
AB  - Bronchial carcinoma was initially diagnosed in a 48-year-old man on the basis of
      radiology showing an apical lung lesion with erosion of the first rib. Biopsy
      ultimately showed this to be osteomyelitis.

PMID- 2001344
TI  - Bronchial perforation secondary to thoracic irradiation for carcinoma of the
      bronchus.

PMID- 2001345
TI  - The influence of breast size on late radiation reaction following excision and
      radiotherapy for early breast cancer.
AB  - The correlation between late radiation reaction and brassiere size (bust and cup
      size) in 133 patients with T1 and T2 breast cancer treated by excision and
      radiotherapy was examined. The radiotherapy schedule used was 4875 cGy in 15 x
      3.25 Gy fractions over 39 days treating five times per fortnight. Patients were
      followed up to a minimum of 2 years (median 4.2 years). The incidence of
      unacceptable late radiation reaction rose significantly with bust size (P less
      than 0.001) and cup size (P less than 0.02). It is intended to treat ladies with
      large breasts with a reduced fraction size or on a daily basis.

PMID- 2001346
TI  - Transcriptional activation of the lipoprotein lipase gene in macrophages by
      dexamethasone.
AB  - The effect of dexamethasone on lipoprotein lipase (LPL) gene expression during
      macrophage differentiation was investigated by using the human monocytic leukemia
      cell line THP-1 and human monocyte-derived macrophages. Addition of dexamethasone
      to THP-1 cells increased steady-state levels of LPL mRNA and LPL mass
      accumulation in the medium during PMA-induced differentiation by 4-fold. Studies
      with human monocyte-derived macrophages showed a similar effect of dexamethasone
      on LPL expression. Peak LPL mRNA levels were achieved 24-h post-dexamethasone
      addition to THP-1 cells. Optimal stimulation of LPL mRNA occurred when
      dexamethasone was added 24 h after induction with PMA. Thereafter, there was
      rapid decline in responsiveness to dexamethasone. Induction of LPL mRNA in THP-1
      cells was completely blocked by actinomycin D, suggesting that induction was
      transcription dependent. The stability of LPL mRNA was not influenced by
      dexamethasone. Treatment of THP-1 cells with PMA led to a 2-fold increase in
      specific binding of dexamethasone and a 4-fold increase in glucocorticoid
      receptor mRNA within 12 h. Thus, dexamethasone stimulates LPL gene expression
      during differentiation of human macrophages, a process that involves induction of
      glucocorticoid receptor synthesis and activation.

PMID- 2001347
TI  - Alpha-bungarotoxin and the competing antibody WF6 interact with different amino
      acids within the same cholinergic subsite.
AB  - In the nicotinic acetylcholine receptors (AChRs), the sequence segment
      surrounding two invariant vicinal cysteinyl residues at positions 192 and 193 of
      the alpha subunit contains important structural component(s) of the binding site
      for acetylcholine and high molecular weight cholinergic antagonists, like snake
      alpha-neurotoxins. At least a second sequence region contributes to the formation
      of the cholinergic site. Studying the binding of alpha-bungarotoxin and three
      different monoclonal antibodies, able to compete with alpha-neurotoxins and
      cholinergic ligands, to a panel of synthetic peptides as representative
      structural elements of the AChR from Torpedo, we recently identified the sequence
      segments alpha 181-200 and alpha 55-74 as contributing to form the cholinergic
      site (Conti-Tronconi et al., 1990). As a first attempt to elucidate the
      structural requirements for ligand binding to the subsite formed by the sequence
      alpha 181-200, we have now studied the binding of alpha-bungarotoxin and of
      antibody WF6 to the synthetic peptide alpha 181-200, and to a panel of peptide
      analogues differing from the parental sequence alpha 181-200 by substitution of a
      single amino acid residue. CD spectral analysis of the synthetic peptide
      analogues indicated that they all have comparable structures in solution, and
      they can therefore be used to analyze the influence of single amino acid residues
      on ligand binding. Distinct clusters of amino acid residues, discontinuously
      positioned along the sequence 181-200, seem to serve as attachment points for the
      two ligands studied, and the residues necessary for binding of alpha-bungarotoxin
      are different from those crucial for binding of antibody WF6. In particular,
      residues at positions 188-190 (VYY) and 192-194 (CCP) were necessary for binding
      of alpha-bungarotoxin, while residues W187, T191, and Y198 and the three residues
      at positions 193-195 (CPD) were necessary for binding of WF6. Comparison of the
      CD spectra of the toxin/peptide complexes, and those obtained for the same
      peptides and alpha-bungarotoxin in solution, indicates that structural changes of
      the ligand(s) occur upon binding, with a net increase of the beta-structure
      component. The cholinergic binding site is therefore a complex surface area,
      formed by discontinuous clusters of amino acid residues from different sequence
      regions. Such complex structural arrangement is similar to the "discontinuous
      epitopes" observed by X-ray diffraction studies of antibody/antigen complexes
      [reviewed in Davies et al. (1988)]. Within this relatively large structure,
      cholinergic ligands bind with multiple points of attachment, and ligand-specific
      patterns of the attachment points exist.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 2001348
TI  - Kinetics of the creatine kinase reaction in neonatal rabbit heart: an empirical
      analysis of the rate equation.
AB  - Here we define the kinetics of the creatine kinase (CK) reaction in an intact
      mammalian heart containing the full range of CK isoenzymes. Previously derived
      kinetic constants [Schimerlik, M. I., & Cleland, W. W. (1973) J. Biol. Chem. 248,
      8418-8423] were refit for the reaction occurring at 37 degrees C. Steady-state
      metabolite concentrations from 31P NMR and standard biochemical techniques were
      determined. 31P magnetization transfer data were obtained to determine
      unidirectional creatine kinase fluxes in hearts with differing total creatine
      contents and differing mitochondrial CK activities during KCl arrest and
      isovolumic work for both the forward reaction (MgATP synthesis) and reverse
      reaction (phosphocreatine synthesis). The NMR kinetic data and substrate
      concentration data were used in conjunction with a kinetic model based on MM-CK
      in solution to determine the applicability of the solution-based kinetic models
      to the CK kinetics of the intact heart. Our results indicated that no single set
      of rate equation constants could describe both the KCl-arrested and working
      hearts. We used our experimental data to constrain the solution-derived kinetic
      model and derived a second set of rate equation constants, which describe the
      isovolumic work state. Analysis of our results indicates that the CK reaction is
      rate limited in the direction of ATP synthesis, the size of the guanidino
      substrate pool drives the measured CK flux in the intact heart, and during
      isovolumic work the CK reaction operates under saturating conditions; that is,
      the substrate concentrations are at least 2-fold greater than the Km or Kim for
      each substrate.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2001349
TI  - Kinetic regulation of yeast NAD-specific isocitrate dehydrogenase by citrate.
AB  - The present results suggest that the enzyme modifier citrate and the substrate
      isocitrate are bound at different sites on yeast NAD-specific isocitrate
      dehydrogenase and that citrate diminishes the binding of the positive effector 5'
      AMP, thereby causing a decreased rate of enzyme catalysis. This interpretation
      differs from the earlier proposal that citrate can replace isocitrate at an
      activator site on the enzyme and can cause inhibition by binding at its catalytic
      site [Atkinson et al. (1965) J. Biol. Chem. 240, 2682]. The present proposal is
      supported by the following observations: At constant subsaturating levels of
      isocitrate, NAD+, and Mg2+ without AMP, up to 10 mM citrate was an activator and
      not an inhibitor. Citrate decreased velocity for AMP-activated enzyme; however,
      with increasing citrate the specific activity with AMP asymptotically approached
      but did not decrease below the level of the enzyme maximally activated by citrate
      in the absence of AMP. When added singly, AMP decreased S0.5 for isocitrate
      without changing the Hill number (n), whereas citrate lowered n without changing
      S0.5 for isocitrate. The difference in action of these modifiers indicated that
      they were bound at separate sites on the enzyme. The binding of citrate appeared
      to cause a conformational change in the protein that lowered the enzyme's
      affinity for AMP. This was consistent with the findings that citrate (or the
      citrate agonist fluorocitrate) (i) resulted in an increase in S0.5 for isocitrate
      with the AMP-activated enzyme and (ii) decreased binding of the positive effector
      analogue TNP-AMP as measured by fluorescence change.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 2001350
TI  - Communication between the active sites in dimeric mercuric ion reductase: an
      alternating sites hypothesis for catalysis.
AB  - Mercuric reductase, a flavoprotein disulfide oxidoreductase, catalyzes the two
      electron reduction of Hg(II) to Hg(0) by NADPH. As with all the members of this
      class of proteins, the enzyme is a dimer of identical subunits with two active
      sites per dimer, each composed of one FAD and catalytically essential residues
      from both subunits. In the enzyme from Tn501, these residues include, at a
      minimum, FAD and cysteines 135 and 140 from one subunit and cysteines 558' and
      559' from the other. With this sort of active site arrangement, the enzyme seems
      perfectly set up for some type of subunit communication. In this report, we
      present results from several titrations, as well as kinetics studies, that, taken
      together, are consistent with the occurrence of subunit communication. In
      particular, the results indicate that pyridine nucleotide complexed dimers of the
      enzyme are asymmetric. Since the EH2-NADPH complex of the enzyme is the relevant
      reductant of Hg(II), these observations suggest that the enzyme may function
      asymmetrically during catalysis. An alternating sites model is proposed for the
      catalytic reduction of Hg(II), where both subunits of the dimer function in
      catalysis, but the steps are staggered and the subunits reverse roles after part
      of the reaction. An attractive feature of this proposal is that it provides a
      reasonable solution to the thermodynamic dilemma the enzyme faces in needing to
      both bind Hg(II) very tightly and reduce it.

PMID- 2001351
TI  - Characterization of an inhibitory metal binding site in carboxypeptidase A.
AB  - The specificity of metal ion inhibition of bovine carboxypeptidase A ([(CPD)Zn])
      catalysis is examined under stopped-flow conditions with use of the fluorescent
      peptide substrate Dns-Gly-Ala-Phe. The enzyme is inhibited competitively by
      Zn(II), Pb(II), and Cd(II) with apparent KI values of 2.4 x 10(-5), 4.8 x 10(-5),
      and 1.1 x 10(-2) M in 0.5 M NaCl at pH 7.5 and 25 degrees C. The kcat/Km value,
      7.3 x 10(6) M-1 s-1, is affected less than 10% at 1 x 10(-4) M Mn(II) or Cu(II)
      and at 1 x 10(-2) M Co(II), Ni(II), Hg(II), or Pt(IV). Zn(II) and Pb(II) are
      mutually exclusive inhibitors. Previous studies of the pH dependence of Zn(II)
      inhibition [Larsen, K. S., & Auld, D. S. (1989) Biochemistry 28, 9620] indicated
      that [(CPD)Zn] is selectively inhibited by a zinc monohydroxide complex, ZnOH+,
      and that ionization of a ligand, LH, in the enzyme's inhibitory site (pKLH 5.8)
      is obligatory for its binding. The present study allows further definition of
      this inhibitory zinc site. The ionizable ligand (LH) is assigned to Glu-270,
      since specific chemical modification of this residue decreases the binding
      affinity of [(CPD)Zn] for Zn(II) and Pb(II) by more than 60- and 200-fold,
      respectively. A bridging interaction between the Glu-270-coordinated metal
      hydroxide and the catalytic metal ion is implicated from the ability of Zn(II)
      and Pb(II) to induce a perturbation in the electronic absorption spectrum of
      cobalt carboxypeptidase A ([(CPD)Co]).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2001352
TI  - Mutant aminoacyl-tRNA synthetase that compensates for a mutation in the major
      identity determinant of its tRNA.
AB  - A single G3.U70 base pair in the acceptor helix is the major determinant for the
      identity of alanine transfer RNAs (Hou & Schimmel, 1988). Introduction of this
      base pair into foreign tRNA sequences confers alanine acceptance on them.
      Moreover, small RNA helices with as few as seven base pairs can be aminoacylated
      with alanine, provided that they encode the critical base pair (Francklyn &
      Schimmel, 1989). Alteration of G3.U70 to G3.C70 abolishes aminoacylation with
      alanine in vivo and in vitro. We describe here the mutagenesis and selection of a
      single point mutation in Escherichia coli Ala-tRNA synthetase that compensates
      for a G3.C70 mutation in tRNAAla. The mutation maps to a region previously
      implicated as proximal to the acceptor end of the bound tRNA. In contrast to the
      wild-type enzyme, the mutant charges small RNA helices that encode a G3.C70 base
      pair. However, the mutant enzyme retains specificity for alanine tRNA and can
      serve as the sole source of Ala-tRNA synthetase in vivo. The results demonstrate
      the capacity of an aminoacyl-tRNA synthetase to compensate through a single amino
      acid substitution for mutations in the major determinant of its cognate tRNA.

PMID- 2001353
TI  - Characterization of DNA metabolizing enzymes in situ following polyacrylamide gel
      electrophoresis.
AB  - We have detected the in situ activities of DNA glycosylase, endonuclease,
      exonuclease, DNA polymerase, and DNA ligase using a novel polyacrylamide activity
      gel electrophoresis procedure. DNA metabolizing enzymes were resolved through
      either native or SDS-polyacrylamide gels containing defined 32P-labeled
      oligonucleotides annealed to M13 DNA. After electrophoresis, these enzymes
      catalyzed in situ reactions and their [32P]DNA products were resolved from the
      gel by a second dimension of electrophoresis through a denaturing DNA sequencing
      gel. Detection of modified (degraded or elongated) oligonucleotide chains was
      used to locate various enzyme activities. The catalytic and physical properties
      of Novikoff hepatoma DNA polymerase beta were found to be similar under both in
      vitro and in situ conditions. With 3'-terminally matched and mismatched [32P]DNA
      substrates in the same activity gel, DNA polymerase and/or 3' to 5' exonuclease
      activities of Escherichia coli DNA polymerase I (large fragment), DNA polymerase
      III (holoenzyme), and exonuclease III were detected and characterized. In
      addition, use of matched and mismatched DNA primers permitted the uncoupling of
      mismatch excision and chain extension steps. Activities first detected in
      nondenaturing activity gels as either multifunctional or multimeric enzymes were
      also identified in denaturing activity gels, and assignment of activities to
      specific polypeptides suggested subunit composition. Furthermore, DNA substrates
      cast within polyacrylamide gels were successfully modified by the exogenous
      enzymes polynucleotide kinase and alkaline phosphatase before and after in situ
      detection of E. coli DNA ligase activity, respectively. Several restriction
      endonucleases and the tripeptide (Lys-Trp-Lys), which acts as an
      apurinic/apyrimidinic endonuclease, were able to diffuse into gels and modify
      DNA. This ability to create intermediate substrates within activity gels could
      prove extremely useful in delineating the steps of DNA replication and repair
      pathways.

PMID- 2001354
TI  - Differential sequence dynamics of homopolymeric and alternating AT tracts in a
      small plasmid DNA.
AB  - The location of OsO4 bispyridine hyper- and hyporeactivity in a small deletion
      derivative of plasmid ColE1 (PTC12, 1727 bp) has been determined for
      approximately 70% of the molecule. Thymine bases in homopolymeric (dA)n.(dT)n
      tracts (n greater than or equal to 4) were always found to be resistant toward
      OsO4 modification. DNA supercoiling did not destabilize these tracts. The extent
      of OsO4 bispyridine reactivity of homopolymeric (dA)n.(dT)n tracts, where n = 3,
      was found to be dependent on the rate of base unpairing of the sequence
      immediately 5' and 3' to the tract. Repressed OsO4 reactivity of thymine bases in
      (dA)3.(dT)3 tracts was observed if immediately both 5' and 3' to the tract were
      stable DNA sequences composed of GC base pairs and/or a homopolymeric (dA)n.(dT)n
      tract (n greater than or equal to 4). Homopolymeric tracts of n = 3 not having
      adjacent sequences with repressed unpairing rates did not show reduced levels of
      OsO4 bispyridine reactivity. Alternating d(TA)n tracts (n greater than or equal
      to 2) were found to exhibit hyperreactivity with OsO4. The extent of this
      hyperreactivity was dependent on the length of the tract and superhelical
      torsional stress. The distribution and frequency of homopolymeric (dA)n.(dT)n (n
      greater than or equal to 4) tracts in Escherichia coli promoter sequences were
      examined, and the possible implications of these tracts on promoter function are
      discussed.

PMID- 2001355
TI  - Crystal structures of cytochrome P-450CAM complexed with camphane, thiocamphor,
      and adamantane: factors controlling P-450 substrate hydroxylation.
AB  - X-ray crystal structures have been determined for complexes of cytochrome P
      450CAM with the substrates camphane, adamantane, and thiocamphor. Unlike the
      natural substrate camphor, which hydrogen bonds to Tyr96 and is metabolized to a
      single product, camphane, adamantane and thiocamphor do not hydrogen bond to the
      enzyme and all are hydroxylated at multiple positions. Evidently the lack of a
      substrate-enzyme hydrogen bond allows substrates greater mobility in the active
      site, explaining this lower regiospecificity of metabolism as well as the
      inability of these substrates to displace the distal ligand to the heme iron.
      Tyr96 is a ligand, via its carbonyl oxygen atom, to a cation that is thought to
      stabilize the camphor-P-450CAM complex [Poulos, T. L., Finzel, B. C., & Howard,
      A. J. (1987) J. Mol. Biol. 195, 687-700]. The occupancy and temperature factor of
      the cationic site are lower and higher, respectively, in the presence of the non
      hydrogen-bonding substrates investigated here than in the presence of camphor,
      underscoring the relationship between cation and substrate binding. Thiocamphor
      gave the most unexpected orientation in the active site of any of the substrates
      we have investigated to date. The orientation of thiocamphor is quite different
      from that of camphor. That is, carbons 5 and 6, at which thiocamphor is primarily
      hydroxylated [Atkins, W. M., & Sligar, S. G. (1988) J. Biol. Chem. 263, 18842
      18849], are positioned near Tyr96 rather than near the heme iron. Therefore, the
      crystallographically observed thiocamphor-P-450CAM structure may correspond to a
      nonproductive complex. Disordered solvent has been identified in the active site
      in the presence of uncoupling substrates that channel reducing equivalents away
      from substrate hydroxylation toward hydrogen peroxide and/or "excess" water
      production. A buried solvent molecule has also been identified, which may promote
      uncoupling by moving from an internal location to the active site in the presence
      of highly mobile substrates.

PMID- 2001356
TI  - High-resolution three-dimensional structure of reduced recombinant human
      thioredoxin in solution.
AB  - The solution structure of recombinant human thioredoxin (105 residues) has been
      determined by nuclear magnetic resonance (NMR) spectroscopy combined with hybrid
      distance geometry-dynamical simulated annealing calculations. Approximate
      interproton distance restraints were derived from nuclear Overhauser effect (NOE)
      measurements. In addition, a large number of stereospecific assignments for beta
      methylene protons and torsion angle restraints for phi, psi, and chi 1 were
      obtained by using a conformational grid search on the basis of the intraresidue
      and sequential NOE data in conjunction with 3JHN alpha and 3J alpha beta coupling
      constants. The structure calculations were based on 1983 approximate interproton
      distance restraints, 52 hydrogen-bonding restraints for 26 hydrogen bonds, and 98
      phi, 71 psi, and 72 chi 1 torsion angle restraints. The 33 final simulated
      annealing structures obtained had an average atomic rms distribution of the
      individual structures about the mean coordinate positions of 0.40 +/- 0.06 A for
      the backbone atoms and 0.78 +/- 0.05 A for all atoms. The solution structure of
      human thioredoxin consists of a five-stranded beta-sheet surrounded by four alpha
      helices, with an active site protrusion containing the two redox-active
      cysteines. The overall structure is similar to the crystal and NMR structures of
      oxidized [Katti, S. K., LeMaster, D. M., & Eklund, H. (1990) J. Mol. Biol. 212,
      167-184] and reduced [Dyson, J. H., Gippert, G. P., Case, D. A., Holmgren, A., &
      Wright, P. (1990) Biochemistry 29, 4129-4136] Escherichia coli thioredoxin,
      respectively, despite the moderate 25% amino acid sequence homology. Several
      differences, however, can be noted. The human alpha 1 helix is a full turn longer
      than the corresponding helix in E. coli thioredoxin and is characterized by a
      more regular helical geometry. The helix labeled alpha 3 in human thioredoxin has
      its counterpart in the 3(10) helix of the E. coli protein and is also longer in
      the human protein. In contrast to these structural differences, the conformation
      of the active site loop in both proteins is very similar, reflecting the perfect
      sequence identity for a stretch of eight amino acid residues around the redox
      active cysteines.

PMID- 2001357
TI  - Folding of staphylococcal nuclease A studied by equilibrium and kinetic circular
      dichroism spectra.
AB  - The urea-induced unfolding of staphylococcal nuclease A has been studied by
      circular dichroism both at equilibrium and by the kinetics of unfolding and
      refolding (pH 7.0 and 4.5 degrees C), as a function of Ca2+ and thymidine 3',5'
      diphosphate (pdTp) concentration. The results are as follows. (1) The unfolding
      transition is shifted to higher concentrations of urea by Ca2+ and pdTp, and the
      presence of both ligands further stabilizes the protein. (2) In the first stage
      of kinetic refolding, the peptide ellipticity changes rapidly within the dead
      time of stopped-flow measurement (15 ms), indicating accumulation of a transient
      intermediate. This intermediate is remarkably less stable than those of other
      globular proteins previously studied. (3) Dependence of the folding and unfolding
      rate constants on urea concentration indicates that the critical activated state
      of folding ("transition state") has considerable structural organization. The
      transition state does not, however, have the capacity to bind Ca2+ and pdTp, as
      indicated by the effects of these ligands on the unfolding rate constant. (4)
      There are at least four different phases in the refolding kinetics in native
      conditions below 1 M urea. In the absence of pdTp, there are two phases in
      unfolding, while in the presence of pdTp the unfolding kinetics show a single
      phase. Some characteristics of the transient intermediate and of the transition
      state for folding are discussed.

PMID- 2001358
TI  - Energy transfer in lactose repressor protein modified with N
      [[(iodoacetyl)amino]ethyl]-5-naphthylamine-1-sulfonate.
AB  - Energy transfer between the two tryptophan residues in the lactose repressor
      protein and the fluorescent moiety of the cysteine-specific reagent N
      [[(iodoacetyl)amino]ethyl]-5-naphthylamine-1-sulfonate (1,5-IAEDANS) has been
      examined. Modification of repressor with this compound did not affect operator or
      inducer binding. 1,5-IAEDANS reacted primarily with Cys140 in wild-type repressor
      [Schneider et al. (1984) Biochemistry 23, 2221]; in the presence of inducer,
      modification at Cys107 increased, while reaction at Cys140 remained unchanged.
      Energy transfer between tryptophans and the AEDANS moiety(ies) in wild-type lac
      repressor occurred with an efficiency of 6.7 +/- 1.9% in the absence and 7.8 +/-
      1.6% in the presence of inducer. The distance between the Trp donor(s) and the
      acceptor in wild-type repressor was calculated to be in the range approximately
      35 A under both conditions. The similarity in efficiency despite large
      differences in the amount of acceptor attached to Cys107 when inducer is bound
      indicates that the AEDANS group at position 107 does not participate
      significantly in energy transfer and that the label at position 140 acts as the
      primary acceptor group. The similarity of energy-transfer efficiency (7.1 +/-
      3.8%) observed for 1,5-IAEDANS-modified monomeric mutant repressor (Y282D)
      indicates that the transfer is primarily intrasubunit in the native tetramer.
      Measurements using two mutant repressors (each with a single tryptophan and
      modified with 1,5-IAEDANS) demonstrated that both tryptophans can serve as donor
      in the energy-transfer process. The W201Y repressor (containing Trp220) exhibited
      a transfer efficiency lower than wild type (5.6 +/- 2.4%), corresponding to a
      slightly larger distance between the donor-acceptor pair in this mutant.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 2001359
TI  - Reductive formation of carbon monoxide from CCl4 and FREONs 11, 12, and 13
      catalyzed by corrinoids.
AB  - In an earlier publication, we reported that corrinoids catalyze the sequential
      reduction of CCl4 to CHCl3, CH2Cl2, CH3Cl, and CH4 with titanium(III) citrate as
      electron donor [Krone, U. E., Thauer, R. K., & Hogenkamp, H. P. C. (1989)
      Biochemistry 28, 4908-4914]. However, the recovery of these products was less
      than 50%, indicating that other products were formed. We now report that, under
      the same experimental conditions, CCl4 is also converted to carbon monoxide.
      These studies were extended to include FREONs 11, 12, 13, and 14. Corrinoids were
      found to catalyze the reduction of CFCl3, CF2Cl2, and CF3Cl to CO and, in the
      case of CFCl3, to a lesser extent, to formate. CF4 was not reduced. The rate of
      CO and formate formation paralleled that of fluoride release. Both rates
      decreased in the series CFCl3, CF2Cl2, CCl4, and CF3Cl. The reduction of CFCl3
      gave, in addition to CO and formate, CHFCl2, CH2FCl, CH3F, C2F2Cl2, and C2F2Cl4.
      The product pattern indicates that the corrinoid-mediated reduction of
      halogenated C1-hydrocarbons involves the intermediacy of dihalocarbenes, which
      may be a reason why these compounds are highly toxic for anaerobic bacteria.

PMID- 2001360
TI  - Degradation of oxidized insulin B chain by the multiproteinase complex macropain
      (proteasome).
AB  - The peptides generated from the degradation of the oxidized B chain of bovine
      insulin by the multiproteinase complex macropain (proteasome) have been analyzed
      by reverse-phase peptide mapping and identified by N-terminal amino acid
      sequencing and composition analysis. Six of the 29 peptide bonds in the insulin B
      chain were found to be rapidly cleaved by macropain. The catalytic center that
      cleaves the Gln4-His5 bond could be distinguished from the center or centers that
      cleave the other preferred bonds by its specific susceptibility to inhibition by
      leupeptin, antipain, chymostatin, and pentamidine, suggesting that macropain
      utilizes at least two distinct catalytic centers for the degradation of this
      model polypeptide. The same effectors simultaneously enhance the rate of cleavage
      at the other susceptible sites in insulin B. The quantitative characteristics of
      this effect indicate that different catalytic centers of the complex may be
      functionally coupled, possibly by an allosteric mechanism or possibly by a
      mechanism in which binding to the catalytic centers is preceded by a rate
      limiting binding of the substrate to a site or sites on the enzyme distinct from
      the catalytic centers. The kinetics of insulin B chain degradation indicate that
      macropain can catalyze sequential hydrolysis of peptide bonds in a single
      substrate molecule via a reaction pathway that involves channeling of peptide
      intermediates between different catalytic centers within the multienzyme complex.
      This capacity for channeling may confer potential physiological advantages of
      increasing the efficiency of amino acid recycling and reducing the pool sizes of
      peptide intermediates that are generated during the degradation of polypeptides
      in the intracellular milieu.

PMID- 2001361
TI  - Protein kinases and protooncogenes: biochemical regulators of the eukaryotic cell
      cycle.

PMID- 2001362
TI  - Human and Escherichia coli cyclophilins: sensitivity to inhibition by the
      immunosuppressant cyclosporin A correlates with a specific tryptophan residue.
AB  - The human T-cell protein cyclophilin shows high affinity for and is the proposed
      target of the major immunosuppressant drug cyclosporin A (CsA). Cyclophilin also
      has peptidyl prolyl cis-trans isomerase activity that is inhibited by CsA with an
      IC50 of 6 nM, while by contrast a homologous PPIase from Escherichia coli has
      been found to be much less sensitive to CsA, shown here to be 500-fold less
      potent at an IC50 of 3000 nM. This E. coli rotamase lacks the single highly
      conserved tryptophan residue of eukaryotic cyclophilins, and we show here that
      mutation of the natural F112 to W112 enhances E. coli rotamase susceptibility to
      CsA inhibition by 23-fold. Correspondingly, the human W121 mutations to F121 or
      A121 yield cyclophilins with 75- and 200-fold decreased sensitivity to CsA, while
      kcat/Km values of rotamase activity in a tetrapeptide assay drop only 2- and 13
      fold, respectively. This complementary gain and loss of CsA sensitivity to
      mutation to or from tryptophan validate the indole side chain as a major
      determinant in immunosuppressant drug recognition and the separation of PPIase
      catalytic efficiency from CsA affinity.

PMID- 2001363
TI  - High-resolution three-dimensional structure of interleukin 1 beta in solution by
      three- and four-dimensional nuclear magnetic resonance spectroscopy.
AB  - The determination of the high-resolution three-dimensional solution structure of
      interleukin 1 beta (IL-1 beta), a protein of 153 residues and 17.4 kDa, which
      plays a central role in the immune and inflammatory responses, has been
      determined by heteronuclear (13C and 15N) three- and four-dimensional NMR
      spectroscopy. The structure is based on 3146 experimental restraints comprising
      2780 distance and 366 torsion angle (phi, psi, and chi 1) restraints. A total of
      32 simulated annealing structures are calculated, and the atomic RMS distribution
      about the mean coordinate positions is 0.41 +/- 0.04 A for the backbone atoms and
      0.82 +/- 0.04 A for all atoms (excluding residue 1 at the N-terminus and residues
      152 and 153 at the C-terminus, which are partially disordered). In the case of
      internal side chains with a surface accessibility of less than or equal to 40%,
      the atomic RMS distribution about the mean coordinate positions for all atoms is
      0.49 +/- 0.03 A. IL-1 beta resembles a tetrahedron and is composed of 12 beta
      strands arranged in three pseudosymmetric topological units, each of which
      comprises 5 strands. Analysis of the mutational data on IL-1 beta in the light of
      the three-dimensional structure suggests the presence of three distinct binding
      sites for the IL-1 receptor on the surface of the protein. It is suggested that
      each of the three immunoglobulin domains which comprise the extracellular portion
      of the IL-1 receptor recognizes one of these sites.

PMID- 2001364
TI  - X-ray absorption fine structure investigation of the zinc transition metal
      binding site of Zn concanavalin A in solution and in the crystal.
AB  - We report details on measurements by the X-ray absorption fine structure (XAFS)
      technique of the conformational changes around the transition metal binding site
      (S1) of the protein concanavalin A induced by crystallization when that site is
      occupied by Zn. A change from hexa- to tetracoordination occurs at the S1 site on
      crystallization when the calcium-binding site (S2) is occupied by a calcium atom.
      When the S2 site is unoccupied, the Zn is pentacoordinated both in solution and
      in the crystal. The average distance to the coordination shell increases with
      coordination number as expected. Conformational changes are detected up to 4.5 A
      from the Zn, the limit of sensitivity of the XAFS technique. When the Zn is
      hexacoordinated, the ligands around the Zn, as determined by XAFS, are consistent
      with the crystal structure determination results of five oxygens and one
      nitrogen. The atom that is released in the tetracoordinated Zn. decreases to five
      is an oxygen atom, and, in addition, the nitrogen is released in the
      tetracoordinated Zn. Thus, when S2 is emptied, the protein gains a ligand about
      the Zn site in the crystal and loses one in solution. These results provide
      direct evidence that the protein conformation can be altered by the
      intermolecular forces of crystallization.

PMID- 2001365
TI  - Distal and proximal ligand interactions in heme proteins: correlations between C
      O and Fe-C vibrational frequencies, oxygen-17 and carbon-13 nuclear magnetic
      resonance chemical shifts, and oxygen-17 nuclear quadrupole coupling constants in
      C17O- and 13CO-labeled species.
AB  - We have obtained the oxygen-17 nuclear magnetic resonance (NMR) spectra of a
      variety of C17O-labeled heme proteins, including sperm whale (Physeter catodon)
      myoglobin, two synthetic sperm whale myoglobin mutants (His E7----Val E7; His E7-
      --Phe E7), adult human hemoglobin, rabbit (Oryctolagus cuniculus) hemoglobin,
      horseradish (Cochlearia armoracia) peroxidase (E.C. 1.11.1.7) isoenzymes A and C,
      and Caldariomyces fumago chloroperoxidase (E.C. 1.11.1.10), in some cases as a
      function of pH, and have determined their isotropic 17O NMR chemical shifts,
      delta i, and spin-lattice relaxation times, T1. We have also obtained similar
      results on a picket fence prophyrin, [5,10,15,20-tetrakis(alpha, alpha, alpha,
      alpha, alpha-pivalamidophenyl)porphyrinato]iron(II) (1-MeIm)CO, both in solution
      and in the solid state. Our results show an excellent correlation between the
      infrared C-O vibrational frequencies, v(C-O), and delta i, between v(C-O) and the
      17O nuclear quadrupole coupling constant (e2qQ/h, derived from T1), and as
      expected between e2qQ/h and delta i. Taken together with the work of others on
      the 13C NMR of 13CO-labeled proteins, where we find an excellent correlation
      between delta i(13C) and v(Fe-C), our results suggest that IR and NMR
      measurements reflect the same interaction, which is thought to be primarily the
      degree of pi-back-bonding from Fe d to CO pi* orbitals, as outlined previously
      [Li, X.-Y., & Spiro, T.G. (1988) J. Am. Chem. Soc. 110, 6024]. The modulation of
      this interaction by the local charge field of the distal heme residue (histidine,
      glutamine, arginine, and possibly lysine) in a variety of species and mutants, as
      reflected in the NMR and IR measurements, is discussed, as is the effect of
      cysteine as the proximal heme ligand.

PMID- 2001366
TI  - A 1H NMR study of human calcitonin in solution.
AB  - Human calcitonin (hCT) has been investigated by NMR at 400 MHz in DMSOd6 and in
      an 85% DMSOd6-15% 1H2O (v/v) cryoprotective mixture. All backbone and side-chain
      resonances have been assigned, and the secondary structure has been determined in
      both solvents. In DMSOd6, the simultaneous presence of d alpha N, dNN, and some
      specific weak medium-range nuclear Overhauser effects, together with the amide
      temperature coefficients and the analysis of the NH-alpha CH spin-spin coupling
      constants, indicates that hCT is highly flexible but with three domains
      (comprising segments Asn3-Gly10, Gln14-Thr21, and Thr25-Ala31) in extended
      conformations which dynamically transform into isolated beta turns in the N- and
      C-terminal regions and into adjacent tight turns, resembling a 3(10) helix
      structure, in the central part. The DMSO-water mixture rigidifies the polypeptide
      chain, favoring an ordered, extended conformation. NOESY data indicate the
      presence of a short double-stranded antiparallel beta sheet in the central region
      made by residues 16-21 and connected by a two-residue hairpin loop formed by
      residues 18 and 19. Two tight turns, formed by residues 3-6 and 28-31, were also
      identified. The central beta sheet does not favor an amphipathic distribution of
      the residues as found for salmon calcitonin [Motta, A., Castiglione Morelli, M.
      A., Goud, N., & Temussi, P. A. (1989) Biochemistry 28, 7998-8002]. This is in
      agreement with the smaller tendency of hCT to form the amphipathic alpha helix,
      postulated to be responsible for the interaction of hCT with lipids. The possible
      role of the cis-trans isomerism of Pro is discussed.

PMID- 2001367
TI  - FTIRS in H2O demonstrates that collagen monomers undergo a conformational
      transition prior to thermal self-assembly in vitro.
AB  - The assembly of type I collagen molecules into native fibrils can be accomplished
      in vitro in solutions at physiological ionic strength and pH by raising the
      temperature above 30 degrees C. The thermal self-assembly reaction exhibits a
      distinct lag phase. This lag phase has been proposed to be evidence for a
      conformational transition in the monomer. Fourier transform infrared spectroscopy
      (FTIRS) is a very sensitive probe of the H-bonded states within the triple helix.
      The carbonyl group spectrum (amide I, 1700-1600 cm-1) has been investigated in
      collagen/H2O solutions at 1 mg/mL under self-assembly conditions from 4 to 34
      degrees C and, in the same range, at a higher ionic strength where self-assembly
      does not occur. The deconvoluted spectra show three very clear bands at
      approximately 1660, 1644, and 1630 cm-1. These bands vary in both frequency
      maxima and relative intensity over the temperature range examined. Spectra were
      also obtained in the amide II and III regions. Spectral changes were evident in
      the 22-26 degrees C range, under fibril-forming conditions, which lead to the
      hypothesis that the triple helix of the semiflexible collagen molecule is
      actually perfected during the lag phase, facilitating nucleation and
      intermolecular interaction. Further spectral changes after fibrils do form show
      that the molecules are once again distorted as they are bent to fit within the
      fibrils.

PMID- 2001368
TI  - Amino acid sequence and molecular characterization of a D-galactoside-specific
      lectin purified from sea urchin (Anthocidaris crassispina) eggs.
AB  - The complete amino acid sequence of a 11.5-kDa subunit of D-galactoside binding
      lectin purified from sea urchin (Anthocidaris crassispina) eggs is presented. The
      105-residue sequence of the subunit was determined by analysis of the intact S
      carbamoylmethylated protein and peptides generated by digestion with
      Achromobacter protease I or Staphylococcus aureus V8 protease. The lectin exists
      as a disulfide-linked homodimer of two subunits; the dimeric form is essential
      for hemagglutination activity. However, the monomeric form obtained by partial
      reduction retains the carbohydrate binding capacity. Neither Ca2+ nor SH reagent
      is essential for hemagglutination or carbohydrate binding. The sequence has no
      similarity to that of any known protein and apparently represents a new type of
      galactoside binding lectin.

PMID- 2001369
TI  - Carbohydrate structures of recombinant soluble human CD4 expressed in Chinese
      hamster ovary cells.
AB  - Infection of T-lymphocytes and macrophages by human immunodeficiency virus (HIV)
      is mediated by the binding of the HIV envelope glycoprotein to the cell-surface
      receptor glycoprotein CD4. A soluble, recombinant CD4 molecule (rCD4), produced
      by expression of a truncated CD4 gene in Chinese hamster ovary (CHO) cells [Smith
      et al. (1987) Science 238, 1704-1707], is in clinical trials as a potential
      therapeutic agent in the treatment of acquired immunodeficiency syndrome (AIDS).
      In the present study, the structures of the Asn-linked oligosaccharides of
      soluble rCD4 have been elucidated. The rCD4 molecule has two potential sites for
      N-glycosylation, Asn-271 and Asn-300. Tryptic glycopeptides containing either of
      the sites were purified by reversed-phase HPLC, and their oligosaccharides were
      released enzymatically. The structures of the oligosaccharides were determined by
      methylation analysis, high-pH anion-exchange chromatography, fast-atom
      bombardment mass spectrometry, and 1H NMR spectroscopy at 500 MHz. Asn-271 was
      found to carry diantennary N-acetyllactosamine-type ("complex") oligosaccharides,
      of which 8% were asialo, 55% were monosialyl, and 37% were disialyl.
      Approximately 18% of these structures contained fucose alpha(1-->6) linked to the
      reducing GlcNAc residue. Two different hybrid structures were found to account
      for 34% of the oligosaccharides attached to Asn-300. The remainder of the
      oligosaccharides attached to Asn-300 were diantennary N-acetyllactosamine-type,
      of which 10% were asialo, 61% were monosialyl, and 29% were disialyl.
      Approximately 9% of the hybrid structures and 40% of the N-acetyllactosamine
      structures at Asn-300 were found to contain fucose alpha(1-->6) linked to the
      innermost GlcNAc residue.

PMID- 2001370
TI  - Efficient and selective photoaffinity labeling of the estrogen receptor using two
      nonsteroidal ligands that embody aryl azide or tetrafluoroaryl azide
      photoreactive functions.
AB  - 3-(4-Azido-2,3,5,6-tetrafluorobenzoyl)-6-hydroxy-2-(4-
      hydroxyphenyl)benzo[b]thiophene 1 (tetrafluoroaryl azide, TFAA) and its protio
      analogue 3-(4-azidobenzoyl)-6- hydroxy-2-(4-hydroxyphenyl)benzo[b]thiophene 2
      (protioaryl azide, PAA), photoaffinity labeling (PAL) reagents for the estrogen
      receptor (ER), have been prepared in high specific activity tritium-labeled form
      (19 Ci/mmol) and shown to undergo selective and efficient photocovalent
      attachment to ER from rat uterus. Both azides 1 and 2 demonstrate high binding
      affinity for ER as determined by both a competitive binding assay (relative
      binding affinities: estradiol = 100; TFAA = 9.3; PAA = 66) and a direct binding
      assay (Kd: estradiol = 0.24 nM; TFAA = 2.64 nM; PAA = 0.37 nM). When unlabeled
      TFAA and PAA are irradiated at greater than 315 nm, they demonstrate site
      specific photoinactivation of ER that reaches 43% and 55%, respectively, by 30
      min. Specific photocovalent attachment to ER can be effected by irradiation of
      the tritium-labeled azides; the covalent attachment efficiency is good (1 = 20
      30%, 2 = ca. 25%) and the selectivity of ER labeling is high. Characterization of
      the photolabeled proteins by SDS-polyacrylamide gel electrophoresis shows
      specific labeling of a major component at Mr 60,000 and a minor species at Mr
      46,000, the same two species that are labeled by [3H]tamoxifen aziridine, a well
      characterized affinity label for ER. The ER-specific antibodies H222Sp gamma and
      D547Sp gamma show a clean precipitation of only these two species. In the MCF-7
      human breast cancer cell line, PAA is a full estrogen agonist in terms of
      stimulation of cell proliferation and induction of progesterone receptor. These
      two azides provide the first system in which the photocovalent attachment
      efficiency of an aryl azide can be compared to its tetrafluorosubstituted aryl
      azide analogue in a complex biological receptor system. Azides 1 and 2 are the
      most efficient and selective PAL reagents prepared to date for ER, and they
      should be useful in further studies of the hormone-binding domain of this
      protein.

PMID- 2001371
TI  - Fusion activity of influenza virus PR8/34 correlates with a temperature-induced
      conformational change within the hemagglutinin ectodomain detected by
      photochemical labeling.
AB  - Fusion of influenza viruses with membranes is catalyzed by the viral spike
      protein hemagglutinin (HA). Under mildly acidic conditions (approximately pH 5)
      this protein undergoes a conformational change that triggers the exposure of the
      "fusion peptide", the hydrophobic N-terminal segment of the HA2 polypeptide
      chain. Insertion of this segment into the target membrane (or viral membrane?) is
      likely to represent a key step along the fusion pathway, but the details are far
      from being clear. The photoreactive phospholipid 1-palmitoyl-2-[11-[4-[3
      (trifluoromethyl)diazirinyl]phenyl] [2-3H]undecanoyl]-sn-glycero-3-phosphocholine
      ([3H]PTPC/11), inserted into the bilayer of large unilamellar vesicles (LUVs),
      allowed us to investigate both the interaction of viruses with the vesicles under
      "prefusion" conditions (pH 5; 0 degrees C) and the fusion process itself
      occurring at elevated temperatures (greater than 15-20 degrees C) only. Despite
      the observed binding of viruses to LUVs at pH 5 and 0 degrees C, labeling of HA2
      was very weak (less than 0.002% of the radioactivity originally present). In
      contrast, fusion could be readily monitored by the covalent labeling of that
      polypeptide chain. We have studied also the effect of temperature on the acid
      induced (pH 5) interaction of bromelain-solubilized HA (BHA) with vesicles.
      Labeling of the BHA2 polypeptide chain was found to show a remarkable correlation
      with the temperature dependence of the fusion activity of whole viruses. A
      temperature-induced structural change appears to be critical for both the
      interaction of BHA with membranes and the expression of fusion activity of intact
      viruses.

PMID- 2001372
TI  - Kinetics and mechanism of the pressure-induced lamellar order/disorder transition
      in phosphatidylethanolamine: a time-resolved X-ray diffraction study.
AB  - By using synchrotron radiation, a movie was made of the X-ray scattering pattern
      from a biological liquid crystal undergoing a phase transition induced by a
      pressure jump. The system studied includes the fully hydrated phospholipid
      dihexadecylphosphatidylethanolamine in the lamellar gel (L beta') phase at a
      temperature of 68 degrees C and a pressure of 9.7 MPa (1400 psig). Following the
      rapid release of pressure to atmospheric the L beta' phase transforms slowly into
      the lamellar liquid crystal (L alpha) phase. The pressure perturbation is applied
      with the intention of producing a sudden phase disequilibrium followed by
      monitoring the system as it relaxes to its new equilibrium condition. Remarkably,
      the proportion of sample in the L alpha phase grows linearly with time, taking 37
      s to totally consume the L beta' phase. The time dependencies of radius, peak
      intensity, and width of the powder diffraction ring of the low-angle (001)
      lamellar reflections were obtained from the movie by image processing. The
      concept of an "effective pressure" is introduced to account for the temperature
      variations that accompany the phase transition and to establish that the observed
      large transit time is indeed intrinsic to the sample and not due to heat exchange
      with the environment. The reverse transformation, L alpha to L beta', induced by
      a sudden jump from atmospheric pressure to 9.7 MPa, is complete in less than 13
      s. These measurements represent a new approach for studying the kinetics of lipid
      phase transitions and for gaining insights into the mechanism of the lamellar
      order/disorder transition.

PMID- 2001373
TI  - Effect of cholesterol on the ethanol-induced interdigitated gel phase in
      phosphatidylcholine: use of fluorophore pyrene-labeled phosphatidylcholine.
AB  - It is now recognized that many amphiphilic molecules such as ethanol can induce
      the formation of the fully interdigitated gel phase (L beta I) in
      phosphatidylcholines (PC's). In the present study, we have developed a simple
      detection method for the L beta I phase using pyrene-labeled PC (PyrPC), which is
      a PC analogue with covalently coupled pyrene moiety at the end of one of its acyl
      chains. The intensity ratio of its fluorescence vibrational bands is a reflection
      of the polarity of the environment of the fluorophore. We have tested this
      fluorophore in several established interdigitated lipid systems, including 1,2
      dipalmitoyl-sn-glycero-3-phosphocholine (1,2-DPPC) in the presence of high
      concentrations of ethanol and 1,2-di-O-hexadecyl-sn-glycero-3-phosphocholine
      (DHPC) and 1,3-dipalmitoyl-sn-glycero-2-phosphocholine (1,3-DPPC) in the absence
      of any additives. We have found in each of these systems that the ratio of the
      intensities of band III (387.5 nm) to band I (376.5 nm) is sensitive to the lipid
      phase change from the noninterdigitated L beta' phase to the interdigitated L
      beta I phase. By comparison of the III/I ratios for PyrPC in the lipid systems
      with the III/I ratios for methylpyrene in organic solvents, it was shown that the
      polarity of the PyrPC environment in the L beta I phase is similar to that of
      pentanol or ethanol. Using this method, we investigated the effect of cholesterol
      on the ethanol induction of the interdigitated gel phase in 1,2-DPPC. We found
      that the ethanol induction of the interdigitated gel phase is prevented by the
      presence of 20 mol % cholesterol.

PMID- 2001374
TI  - The DNA sequence at echinomycin binding sites determines the structural changes
      induced by drug binding: NMR studies of echinomycin binding to [d(ACGTACGT)]2 and
      [d(TCGATCGA)]2.
AB  - The complexes formed between the cyclic octadepsipeptide antibiotic echinomycin
      and the two DNA octamers [d(ACGTACGT)]2 and [d(TCGATCGA)]2 have been investigated
      by using one- and two-dimensional proton NMR spectroscopy techniques. The results
      obtained for the two complexes are compared to each other, to the crystal
      structures of related DNA-echinomycin complexes, and to enzymatic and chemical
      footprinting results. In the saturated complexes, two echinomycin molecules bind
      to each octamer by bisintercalation of the quinoxaline moieties on either side of
      each CpG step. Binding of echinomycin to the octamer [d(ACGTACGT)]2 is
      cooperative so that only the two-drug complex is observed at lower drug-DNA
      ratios, but binding to [d(TCGATCGA)]2 is not cooperative. At low temperatures,
      both the internal and terminal A.T base pairs adjacent to the binding site in the
      [d(ACGTACGT)]2-2 echinomycin complex are Hoogsteen base paired (Gilbert et al.,
      1989) as observed in related crystal structures. However, as the temperature is
      raised, the internal A.T Hoogsteen base pairs are destabilized and are observed
      to be exchanging between the Hoogsteen base-paired and an open (or Watson-Crick
      base-paired) state. In contrast, in the [d(TCGATCGA)]2-2 echinomycin complex, no
      A.T Hoogsteen base pairs are observed, the internal A.T base pairs appear to be
      stabilized by drug binding, and the structure of the complex does not change
      significantly from 0 to 45 degrees C. Thus, the structure and stability of the
      DNA in echinomycin-DNA complexes depends on the sequence at and adjacent to the
      binding site. While we conclude that no single structural change in the DNA can
      explain all of the footprinting results, unwinding of the DNA helix in the drug
      DNA complexes appears to be an important factor while Hoogsteen base pair
      formation does not.

PMID- 2001375
TI  - Mutations in 5S DNA and 5S RNA have different effects on the binding of Xenopus
      transcription factor IIIA.
AB  - The effects on TFIIIA binding affinity of a series of substitution mutations in
      the Xenopus laevis oocyte 5S RNA gene were quantified. These data indicate that
      TFIIIA binds specifically to 5S DNA by forming sequence-specific contacts with
      three discrete sites located within the classical A and C boxes and the
      intermediate element of the internal control region. Substitution of the
      nucleotide sequence at any of the three sites significantly reduces TFIIIA
      binding affinity, with a 100-fold reduction observed for substitutions in the box
      C subregion. These results are consistent with a direct interaction of TFIIIA
      with specific base pairs within the major groove of the DNA. A comparison of the
      TFIIIA binding data for the same mutations expressed in 5S RNA indicates that the
      protein does not make any strong sequence-specific contacts with the RNA.
      Although the protein footprinting sites on the 5S DNA and 5S RNA are coincident,
      nucleotide substitutions in 5S RNA which moderately reduce TFIIIA binding
      affinity do not correspond at all to the three specific TFIIIA interaction sites
      within the gene. The implications of these results for models which attempt to
      reconcile the DNA and RNA binding activities of TFIIIA by proposing a common
      structural motif for the two nucleic acids are discussed.

PMID- 2001376
TI  - Characterization of a cDNA for chicken osteopontin: expression during bone
      development, osteoblast differentiation, and tissue distribution.
AB  - The chicken bone phosphoprotein (approximately 66-kDa BPP) is a major
      noncollagenous component of bone and is the major phosphoprotein synthesized by
      cultured chicken embryo osteoblasts [Gotoh, Y., Gerstenfeld, L. C., & Glimcher,
      M. J. (1990) Eur. J. Biochem. 87, 49-58]. A cDNA clone for this protein was
      isolated from an expression library made from embryonic chicken bone mRNA. The
      complete primary protein sequence of 264 amino acids was deduced from the cDNA
      sequence inclusive of a 16 amino acid signal peptide sequence and terminated by 4
      in-frame stop sequences. A sequence alignment indicated an approximate 35%
      overall similarity in protein sequence between the avian approximately 66-kDa BPP
      and the mammalian protein osteopontin, while at the nucleotide level 60%
      similarity was observed. Features of this sequence which showed the greatest
      similarity to mammalian osteopontin included a region in which seven of nine
      consecutive residues are aspartic acid, a recognition sequence for integrin
      mediated cell binding (-Arg-Gly-Asp), and four possible recognition sequences for
      phosphorylation by casein kinase II. Hybridization analysis indicated a message
      of 1.5 kb found predominantly in bone and kidney. The mRNA was inducible in
      phorbol ester treated primary cultures of chondrocytes which show no expression
      under normal growth conditions. A temporal induction was seen during osteoblastic
      differentiation both in vivo and in vitro, thus suggesting that regulation of the
      approximately 66-kDa BPP is under transcriptional control during osteoblast
      development. In summary, both the protein's primary structure and its biological
      features suggest that it is the avian homologue to mammalian protein osteopontin.

PMID- 2001377
TI  - Metabolic origin of urinary 3-hydroxy dicarboxylic acids.
AB  - 3-Hydroxy dicarboxylic acids with chain lengths ranging from 6 to 14 carbons are
      excreted in human urine. The urinary excretion of these acids is increased in
      conditions of increased mobilization of fatty acids or inhibited fatty acid
      oxidation. Similar urinary profiles of 3-hydroxy dicarboxylic acids were also
      observed in fasting rats. The metabolic genesis of these urinary 3-hydroxy
      dicarboxylic acids was investigated in vitro with rat liver postmitochondrial and
      mitochondrial fractions. 3-Hydroxy monocarboxylic acids ranging from 3
      hydroxyhexanoic acid to 3-hydroxyhexadecanoic acid were synthesized. In the rat
      liver postmitochondrial fraction fortified with NADPH, these 3-hydroxy fatty
      acids with carbon chains equal to or longer than 10 were oxidized to (omega - 1)-
      and omega-hydroxy metabolites as well as to the corresponding 3-hydroxy
      dicarboxylic acids. 3-Hydroxyhexanoic (3OHMC6) and 3-hydroxyoctanoic (3OHMC8)
      acids were not metabolized. Upon the addition of mitochondria together with ATP,
      CoA, carnitine, and MgCl2, the 3-hydroxy dicarboxylic acids were converted to 3
      hydroxyoctanedioic, trans-2-hexenedioic, suberic, and adipic acids. In the urine
      of children with elevated 3-hydroxy dicarboxylic acid levels, 3OHMC6, 3OHMC8, 3
      hydroxydecanoic, 3,10-dihydroxydecanoic, 3,9-dihydroxydecanoic, and 3,11
      dihydroxydodecanoic acids were identified. On the basis of these data, we propose
      that the urinary 3-hydroxy dicarboxylic acids are derived from the omega
      oxidation of 3-hydroxy fatty acids and the subsequent beta-oxidation of longer
      chain 3-hydroxy dicarboxylic acids. These urinary 3-hydroxy dicarboxylic acids
      are not derived from the beta-oxidation of unsubstituted dicarboxylic acids.

PMID- 2001378
TI  - Oxidation and reduction of 4-hydroxyalkenals catalyzed by isozymes of human
      alcohol dehydrogenase.
AB  - 4-Hydroxyalkenals, natural cytotoxic products of lipid peroxidation, are
      substrates for human alcohol dehydrogenases (ADH). Class I and II ADHs reduce
      aliphatic 4-hydroxyalkenals with chain lengths of from 5 to 15 carbons at pH 7
      with kcat and Km values comparable to simple aliphatic aldehydes of the same
      chain length. Class II is particularly effective in the reduction with kcat
      values as high as 3300 min-1 for 4-hydroxyundecenal. Class III ADH is essentially
      inactive toward all of these substrates. The class I and II isozymes also
      catalyze the oxidation of the 4-hydroxy group at pH 10. However, during the
      reaction, an NAD(+)-dependent irreversible partial inactivation of the alpha beta
      1 isozyme is observed which is attributed, with the aid of computer graphics
      modeling, to selective modification of the alpha subunit. Both ethanol and 1,10
      phenanthroline, known to compete with conventional substrates, instantaneously,
      reversibly, and competitively inhibit 4-hydroxyalkenal reduction and oxidation,
      indicating that 4-hydroxyalkenals bind at the same site as do conventional
      substates. The fact that the class II enzyme pi pi-ADH so far is found only in
      the liver and that the 4-hydroxyalkenals are the best substrates known for this
      isozyme suggest that it may play a significant role in cellular defenses in the
      conversion of the cytotoxic aldehydes to the less reactive alcohols.

PMID- 2001379
TI  - Porcine cytosolic aspartate aminotransferase reconstituted with [4'-13C]pyridoxal
      phosphate. pH- and ligand-induced changes of the coenzyme observed by 13C NMR
      spectroscopy.
AB  - Apoenzyme samples of aspartate aminotransferase (AspAT) purified from the
      cytosolic fraction of pig heart were reconstituted with [4'-13C]pyridoxal 5'
      phosphate (pyridoxal-P). The 13C NMR spectra of AspAT samples thus generated
      established the chemical shift of 165.3 ppm for C4' of the coenzyme bound as an
      internal aldimine with lysine 258 of the enzyme at pH 5. In the absence of
      ligands the chemical shift of C4' was shown to be pH dependent, shifting 5 ppm
      upfield to a constant value of 160.2 ppm above pH 8, the resulting pKa of 6.3 in
      agreement with spectrophotometric titrations. The addition of the competitive
      inhibitor succinate to the internal aldimine raises the pKa of the imine to 7.8,
      consistent with the theory of charge neutralization in the active site. In the
      presence of saturating concentrations of 2-methylaspartic acid the C4' signal of
      the coenzyme was shown to be invariant with pH and located at 162.7 ppm, midway
      between the observed chemical shifts of the protonated and unprotonated forms of
      the internal aldimine. The intermediate chemical shift of the external aldimine
      complex is thought to reflect the observation of an equilibrium mixture composed
      of roughly equal populations of the protonated ketoenamine and a dipolar anion
      species, corresponding to their respective spectral bands at 430 and 360-370 nm.
      Conversion to the pyridoxamine form was accomplished via reaction of the internal
      aldimine with L-cysteinesulfinate or by reduction with sodium borohydride, and
      the resulting C4' chemical shifts were identified by difference spectroscopy.
      Finally, the line widths of the C4' resonance under the various conditions were
      measured and qualitatively compared. The results are discussed in terms of the
      current mechanism and molecular models of the active site of AspAT.

PMID- 2001380
TI  - The structure of the dihaem cytochrome b of fumarate reductase in Wolinella
      succinogenes: circular dichroism and sequence analysis studies.
AB  - The fumarate reductase from Wolinella succinogenes contains two haem groups with
      markedly different midpoint potentials (-20 mV and -200 mV). The enzyme is made
      up of three subunits, the lipophilic one of which (cytochrome b) ligates the
      haems. Circular dichroism (CD) spectroscopy has been applied to the reductase in
      order to obtain information on the structure of the haems and of their
      environment. This approach is integrated with amino acid sequence comparison of
      the cytochrome b with other quinone-reacting membrane haemoproteins for
      predicting the axial ligands of the haems as well as their location relative to
      the membrane. The following results have been obtained: (1) the CD spectra in the
      Soret region show exciton coupling indicating haem-haem interaction, which is
      particularly evident in the reduced state and disappears upon denaturation of the
      enzyme; (2) The apoprotein of cytochrome b is predicted to consist of five
      hydrophobic helices (helices A-D and cd), four of which should span the membrane.
      Helices A, B, C and cd contain a histidine residue each which possibly forms one
      of the ligands of the haems. It is proposed that haem b (-20 mV) is ligated by
      H44 and H93, and haem b (-200 mV) by H143 and H182.

PMID- 2001381
TI  - Use of NAD(P)H and flavoprotein fluorescence signals to characterize the redox
      state of pyridine nucleotides in epididymal bull spermatozoa.
AB  - The redox behaviour of the NAD(P) system and flavoproteins was registered by
      simultaneous fluorescence measurements in epididymal bull spermatozoa. The
      flavoprotein fluorescence signal can nearly exclusively be attributed to an NAD
      linked enzyme, alpha-lipoamide dehydrogenase (Em7.4 = -286 mV). A comparison of
      intact with digitonin-permeabilized spermatozoa revealed that about 50% of the
      total NAD(P)H fluorescence signal was of mitochondrial origin. Under equilibrium
      conditions, the midpoint potentials of the NAD(P)H fluorescence signal of both
      compartments were almost identical (-300 mV). When lactate was present as
      substrate, 1 mM caffeine increased respiration oxidizing the NAD(P)H system in
      both mitochondria and cytosol. This indicates a close relationship of the two NAD
      pools in spermatozoa.

PMID- 2001382
TI  - Unfolding-refolding behaviour of chicken egg white ovomucoid and its correlation
      with the three domain structure of the protein.
AB  - The urea and heat-induced unfolding-refolding behaviours of chicken egg white
      ovomucoid and its four fragments representing domains I, II + III, I + II and III
      were systematically investigated in 0.06 M sodium phosphate buffer (pH 7.0) by
      difference spectral measurements. The effect of temperature on ovomucoid and its
      fragments was also studied in 0.05 M sodium acetate buffer (pH 5.0) and in
      presence of 2 M urea at pH 7.0. Intrinsic viscosity data showed that ovomucoid
      and its different fragments did not lose any significant amount of their
      structure under mild acidic conditions (pH 4.6). Difference spectral results
      showed extensive disruption of the native structure by urea or temperature.
      Isothermal transitions showed single-step for domain I, domain I + II and domain
      III, and two-step having one stable intermediate, for ovomucoid and its fragment
      representing domain II + III. However, the presence of intermediate was not
      detected when the transitions were studied with temperature at pH 7.0.
      Strikingly, the single-step thermal transitions of ovomucoid and its fragment
      representing domain II + III, became two-step when measured either at pH 5.0 or
      in presence of 2 M urea at pH 7.0. Analysis of the equilibrium data on urea and
      heat denaturation showed that the second transition observed with ovomucoid or
      domain II + III represent the unfolding of domain III. The kinetic results of
      ovomucoid and its fragments indicate that the protein unfolds with three kinetic
      phases. A comparison of three rate constants for the unfolding of intact
      ovomucoid with that of its various fragments revealed that domain I, II and III
      of the protein correspond to the three kinetic phases having rate constants
      0.456, 0.120 and 0.054 min-1, respectively. These data have led us to conclude:
      (i) the unusual stability of ovomucoid towards various denaturants, including
      temperature, is due to its domain III, (ii) initiation of the folding of the
      ovomucoid molecule starts from its NH2-terminal region which probably provides
      the nucleation site for the formation of the subsequent structure and (iii)
      domains I and II have greater mutual recognition between them as compared to the
      recognition either of them have with domain III.

PMID- 2001383
TI  - Analysis of the acid and alkaline dissociation of earthworm hemoglobin, Lumbricus
      terrestris, by front-face fluorescence spectroscopy.
AB  - The steady-state fluorescence properties of the multisubunit hemoglobin isolated
      from the earthworm, Lumbricus terrestris, were studied by front-face fluorometry.
      Acid and alkaline dissociation of this high-molecular-weight hemoglobin were
      examined over the pH range 3.7-12.5 using different liganded states (oxy, CO,
      met). The relative intensity of the emission maximum at 320 nm (exc. 280 nm) is
      ligand-dependent increasing as follows: oxy less than deoxy less than CO less
      than met at pH 7.0. The intensity of the emission maximum of oxyhemoglobin at the
      alkaline acid end point, pH 10.5 (333 nm), is significantly greater than that
      observed at the acid end point, pH 4.18 (320 nm), suggesting different subunit
      dissociation. The spectra of oxyhemoglobin at pH 4.18 and the spectrum of
      carbonmonoxy hemoglobin at pH 7.0 in the presence of 1 M magnesium chloride were
      almost identical, indicating similar subunit dissociation. Difference spectrum
      (pH 9.0-7.2) of fluorescence emission (exc. 305) resulted in a maximum at 341 nm,
      indicative of tyrosinate formation. This suggests that tyrosine(s) may also be
      located at the subunit interface(s) of this hemoglobin. These studies indicate
      that several aromatic amino acid residues are associated with the critical sites
      of subunit interactions within this molecule. Analysis of the fluorescence
      spectra also suggests that the formation of different subunit species resulting
      from acid and alkaline dissociation cannot be ruled out.

PMID- 2001384
TI  - Substrate specificity of solvent viscosity effects in carboxypeptidase A
      catalyzed peptide hydrolysis.
AB  - We have investigated the viscosity of carboxypeptidase A catalyzed Bz-Gly-Phe
      hydrolysis at pH 7.5 (Tris) and 0.5 mol.l-1 NaCl over the range 10-100 mp, varied
      by addition of glycerol or sucrose. In contrast to previous reports of strong
      viscosity effects on the corresponding Cbz-Ala-Ala-Ala hydrolysis, both the
      catalytic constant and the Michaelis constant are virtually independent of
      viscosity over the 10-fold range investigated. Furthermore, the CD spectra of
      carboxypeptidase A in the high-viscosity media point to no change in the alpha
      helix and beta-sheet structure in these media. The data are compatible either
      with a compacter, more rigid enzyme-substrate structure or with a more prominent
      role of intramolecular nuclear reorganization compared to protein reorganization
      for Bz-Gly-Phe than for Cbz-Ala-Ala-Ala. These views can be given a preciser
      frame in terms of stochastic chemical rate theory.

PMID- 2001385
TI  - The importance of glycine-30 for enzymatic activity of phospholipase A2.
AB  - The nearly conserved glycine-30 in porcine pancreatic phospholipase A2 has been
      replaced by serine. The resulting mutant G30S was expressed in Escherichia coli,
      purified and characterized. The mutation caused a significant drop in enzymatic
      activity towards monomeric and aggregated substrates, but had a limited effect on
      substrate binding. In contrast the affinity for calcium ions, the essential
      cofactor, was reduced 10-fold. The reduced enzymatic activity is attributed to a
      reduced stabilization of the transition state. The results are discussed in view
      of naturally occurring inactive phospholipase A2 homologues from snake venom.

PMID- 2001386
TI  - Specific modification of Escherichia coli RNA polymerase with monomercury
      derivative of fluorescein acetate.
AB  - The method of specific modification of RNA polymerase with a monomercuric
      fluorescein derivative, fluorescein-monomercuriacetate (FMMA), is proposed. Under
      an appropriate condition of modification, FMMA is capable of mercaptid bonding
      with one of the alpha-subunits. It is shown that covalent modification with FMMA
      does not affect the kinetic parameters (KB and k2) of RNA synthesis nor does it
      lead to the inhibition of the overall RNA synthesis. The spectral characteristics
      of FMMA covalently bound to RNA polymerase were found to be sensitive to some
      temperature-induced conformational alterations of RNA polymerase, indicating that
      the labeled enzyme allows study of conformational behaviour of RNA polymerase
      during its functioning.

PMID- 2001387
TI  - Stereoselective formation of bis(alpha-aminoacyl) esters of 5'-AMP suggests a
      primitive peptide synthesizing system with a preference for L-amino acids.
AB  - In the biosynthesis of proteins, each amino acid passes from the aminoacyl
      adenylate to become an amino acid ester and finally a 2' (3') peptidyl ester of
      the AMP residue at the end of a tRNA. Consequently, the chemistry of protein
      synthesis is the chemistry of aminoacyl and peptidyl AMP. Our data has revealed
      properties of 5'-AMP and its esters which should allow the preferential catalytic
      synthesis of L-amino acid peptides via a bis(2', 3'-aminoacyl) ester
      intermediate. Results in this paper concern one step in the proposed process and
      show that preexisting Ac-L-Phe monoester reacts about 2.5-times faster to form
      diester than preexisting Ac-D-Phe monoester.

PMID- 2001388
TI  - Acyloxybenzyl halides, inhibitors of elastases.
AB  - 3-Benzyl-6-chloromethyl-3,4-dihydrocoumarin inhibits human leucocyte elastase
      (HLE) and porcine pancreatic elastase (PPE) through a mechanism-based process
      characterized by the following apparent enzyme-inhibitor dissociation constants,
      Ki, and limiting inactivation rate constants k2: 200 microM (HLE), 69 microM
      (PPE) and 5.10(-2) s-1 (HLE), 17.7.10(-2) s-1 (PPE) at pH 8.0, 37 degrees C.
      Bis(4-acyloxyphenyl)methane derivatives with a benzylic halogen as potential
      leaving group have also been synthesized and studied. They transiently inactivate
      PPE and HLE through the formation of an acyl-enzyme.

PMID- 2001389
TI  - A kinetic and equilibrium study of the denaturation of aspartic proteinases from
      the fungi, Endothia parasitica and Mucor miehei.
AB  - Kinetic and equilibrium analyses of the denaturation of Endothia parasitica and
      Mucor miehei aspartic proteinases were performed using enzyme activity and
      ultraviolet absorption as indices of denaturation. Denaturation of these
      proteinases was shown to be irreversible, suggesting that the conformations of
      these aspartic proteinases may be predetermined in their zymogens. Thermal and
      guanidine hydrochloride denaturation of these proteinases produced first-order,
      two-state, kinetic behaviour. Equilibrium unfolding transitions of these
      proteinases were highly cooperative but not entirely coincident in the two
      indices employed, suggesting some deviation from two-state character. Oxidation
      to remove 37.8% of the carbohydrate of M. miehei glycoproteinase with sodium
      metaperiodate resulted in a substantial decrease in both kinetic and equilibrium
      stabilities without modification of the amino acid composition or specific
      activity. In addition, gel filtration subsequent to equilibrium studies indicated
      that partial removal of the carbohydrate from M. miehei proteinase promoted
      autolysis under denaturing conditions.

PMID- 2001390
TI  - Enhancement of insect antifreeze protein activity by antibodies.
AB  - Antifreeze proteins, produced by many cold water marine teleost fish and
      terrestrial arthropods (insects, spiders, etc.), inhibit ice crystal growth by a
      non-colligative mechanism, probably by adsorbing onto the surface of potential
      seed ice crystals and thereby blocking growth at preferred growth sites. In this
      study it is demonstrated that the activity of two insect antifreeze proteins is
      greatly increased by the addition of specific rabbit polyclonal antibodies to the
      antifreezes. A model is presented which suggests that the enhancement occurs
      because the antifreeze-antibody complex, being much larger than the antifreeze
      protein alone (a minimal 7-8-fold increase in size), blocks a larger area of the
      ice crystal surface and extends further above the surface, thus requiring the
      temperature to be further lowered before crystal growth proceeds. This idea is
      further supported by the finding that addition of goat anti-rabbit IgG to the
      antifreeze protein + anti-antifreeze protein antibody complexes further enhanced
      activity.

PMID- 2001391
TI  - A re-appraisal of multiplicity of endoglucanase I from Trichoderma reesei using
      monoclonal antibodies and plasma desorption mass spectrometry.
AB  - An endo beta-1,4-glucanase (EC 3.2.1.4, 1.4-(1,3;1,4)-beta-D-glucan 4
      glucanhydrolase) was purified to apparent homogeneity from culture filtrates of
      Trichoderma reesei QM 9414. Identity of the protein with endoglucanase I (EG I)
      was examined by subjecting CNBr fragments of the protein to analysis by plasma
      desorption mass spectrometry. Seven non-glycosylated fragments, mapped on the eg1
      gene sequence, could be identified, hence proving at least 39.4% identity of the
      amino acid sequence. No sign for microheterogeneity was observed. Purified EG I
      was used to prepare monoclonal antibodies. 17 stable clones were obtained, of
      which one--Mab EG 3--was used to analyze several commercial T. reesei cellulase
      preparations as well as culture filtrates from T. pseudokoningii and T.
      longibrachiatum for the presence of EG I. Most of them contained immunoreactive
      material migrating as a prominent 50-55 kDa band on SDS-PAGE, resembling EG I,
      but in some instances additional lower molecular weight bands were also observed.
      Cultivation of T. reesei at low pH led to an increase of these lower molecular
      weight bands. EG I was rather stable against proteolysis by papain in vitro, but
      after prolonged treatment, immunopositive products of 50 and 45 kDa were produced
      at the expense of the 55 kDa band. Our monoclonal antibodies failed to react with
      a low-molecular-weight endoglucanase, which was previously shown to be detectable
      with polyclonal antiserum against EG I. However, all monoclonals reacted with a
      118 kDa protein which is most probably a dimer of EG I. These results are
      discussed with respect to the occurrence of multiple forms of EG I in T. reesei
      cellulase preparations.

PMID- 2001392
TI  - Conformational change induced by coenzyme binding to bovine liver dihydrofolate
      reductase: a spectrofluorimetric study.
AB  - When NADPH was added in excess to a bovine liver DHFR solution, a fluorescence
      peak due to an energy transfer mechanism was apparent at 450 nm. It did not vary
      over time. The intrinsic fluorescence peak of DHFR at 320 nm was quenched and
      this phenomenon increased over the time-course after NADPH addition. This result
      was ascribed to a slow DHFR conformational change induced by NADPH binding, which
      has never been previously described in such a long time scale (more than 30 min).
      A kinetic scheme accounting for this mechanism has been proposed. Furthermore,
      this interconversion between two protein conformers led to an increase in the
      initial apparent rate of the enzymatic reaction catalyzed by DHFR.

PMID- 2001393
TI  - EXAFS analysis of the pH dependence of the blue-copper site in amicyanin from
      Thiobacillus versutus.
AB  - The room temperature Cu K-edge EXAFS (extended X-ray absorption fine structure)
      spectrum of reduced and oxidized amicyanin, the blue copper protein from
      Thiobacillus versutus, was measured at low and high pH. The data interpretation
      was partly based on independent NMR evidence for the occurrence of a ligand
      histidine protonation at low pH (pKa = 6.9) in the reduced protein. In the
      oxidized protein two nitrogen-donors (from two histidines; Cu-N distances 1.95
      2.01 A and 1.86-1.89 A) and a sulfur-donor (from a cysteine; Cu-S distance 2.11
      2.13 A) were identified and the coordination appears independent of pH. Upon
      reduction at high pH the Cu-S bond and one of the Cu-N bonds lengthen slightly
      (from 2.11 to 2.19 A and from 2.01 to 2.18 A, respectively). Upon lowering of the
      pH one of the N-donors of the Cu in reduced amicyanin disappears from the Cu
      EXAFS and a second S-donor (from a methionine) becomes visible at 2.41 A from the
      Cu. The Debye-Waller factors are compatible with a Cu-N vibrational stretch
      frequency in the range of 150-250 cm-1 and one greater than 285 cm-1, and a Cu-S
      vibrational stretch frequency of about 150 cm-1 (Cu-Smet; reduced amicyanin at
      low pH) and one in the range of 230-800 cm-1 (Cu-Scys).

PMID- 2001394
TI  - The glucocorticoid receptor.

PMID- 2001395
TI  - Inhibitory action of phospholipid-interacting drugs on transcription initiation
      in a nuclear extract of Ehrlich ascites tumor cells.
AB  - Drugs with affinity for phospholipids, such as chlorpromazine, verapamil,
      tetracaine and imipramine, were found to inhibit accurate transcription from
      adenovirus 2 major late promoter in a nuclear extract of Ehrlich ascites tumor
      cells. The transcription activity of the nuclear extract inhibited by
      chlorpromazine was restored by addition of acidic phospholipids. The nuclear
      extract was also shown to lose transcription activity when treated with
      phospholipase A2. Chlorpromazine was found to inhibit transcription at the step
      of initiation, not elongation. Moreover, it did not affect the activity of
      purified RNA polymerase II, suggesting the interaction of phospholipids with
      transcription factors in the nuclear extract. Some transcription factors in the
      nuclear extract were found to have affinity for cardiolipin, and were
      precipitated with excess cardiolipin. The transcription factors precipitated with
      cardiolipin could be solubilized with guanidine hydrochloride, and restored the
      transcription activity of the cardiolipin-treated nuclear extract.

PMID- 2001396
TI  - Isolation and characterization of a human cDNA encoding uracil-DNA glycosylase.
AB  - DNA repair of genetic information is an essential defense mechanism, which
      protects cells against mutation and transformation. The biochemistry of human DNA
      repair is in its beginning stages. Our research has concentrated on the enzymes
      involved in the removal of atypical bases from DNA. We present information on the
      identification and characterization of a cDNA isolate encoding uracil-DNA
      glycosylase. Uracil-DNA glycosylase was purified to homogeneity from HeLa S3
      cells and used to generate polyclonal antibodies. These antibodies were in turn
      used to isolate a uracil-DNA glycosylase specific cDNA from a human T cell
      (Jurkat) lambda-gt11 library. The identity of this 1.25 kb cDNA was verified
      using in vitro transcription and translation systems to generate specific uracil
      DNA glycosylase activity. Sequence data revealed a 327 amino acid open reading
      frame, which encodes a protein with a predicted molecular weight of 35351. No
      significant amino acid homology was found between this human uracil-DNA
      glycosylase and the glycosylases of yeast, Escherichia coli, herpes simplex
      virus, or a recently identified 26,000 Da species of human uracil-DNA
      glycosylase. This apparent lack of homology prompted an investigation of uracil
      DNA glycosylase in a variety of eukaryotic species. Western analysis demonstrated
      the presence of a 36 kDa uracil-DNA glycosylase protein in human fibroblast,
      human placental and Vero cell extracts. Interestingly, these antibodies did not
      detect glycosylase protein in Chinese hamster ovary (CHO) or mouse NIH3T3
      fibroblast cells. Under conditions of reduced stringency, Southern blot analysis
      of BamHI digested DNA from human fibroblasts, human placental cells and Vero
      cells revealed common 12 kb and 3 kb fragments. In contrast, using the same
      reduced stringency protocol, 6 and 8 kb fragments for CHO and NIH3T3 DNA were
      seen, respectively, as well as a common 3 kb fragment. Under more stringent wash
      conditions, the common 3 kb band was absent in all samples analyzed, and no
      hybridization signal was detected from DNA of hamster or mouse origin. The lack
      of immunological reactivity between the human uracil-DNA glycosylase and the
      rodent forms is therefore reflected at the genetic level as well. This
      distinction in human and CHO hybridization patterns enabled us to localize this
      human uracil-DNA glycosylase cDNA to chromosome 5 by somatic cell hybridization.

PMID- 2001397
TI  - Cloning and characterization of an amidase gene from Rhodococcus species N-774
      and its expression in Escherichia coli.
AB  - For investigation of an unknown open reading frame which is present upstream of
      the nitrile hydratase (NHase) gene from Rhodococcus sp. N-774, a longer DNA
      fragment covering the entire gene was cloned in Escherichia coli. Nucleotide
      sequencing and detailed subcloning experiments predicted a single open reading
      frame consisting of 521 amino acid residues of Mr 54,671. The amino acid
      sequence, especially its NH2-terminal portion, showed significant homology with
      those of indoleacetamide hydrolases from Pseudomonas savastanoi and Agrobacterium
      tumefaciens, and acetamidase from Aspergillus nidulans. The 521-amino acid coding
      region was therefore expressed by use of the E. coli lac promoter in E. coli, and
      was found to direct a considerable amidase activity. This amidase hydrolyzed
      propionamide efficiently, and also hydrolyzed, at a lower efficiency, acetamide,
      acrylamide and indoleacetamide. These data clearly show that the unknown open
      reading frame present upstream of the NHase coding region encodes an amidase.
      Because the TAG translational stop codon of the amidase is located only 75 base
      pairs apart from the ATG start codon of the alpha-subunit of NHase, these genes
      are probably translated in a polycistronic manner.

PMID- 2001398
TI  - Classes of autonomously replicating sequences are found among early-replicating
      monkey DNA.
AB  - Thirteen new independent clones of origin-enriched sequences (ors) that are
      capable of autonomous replication have been identified from a library of 100 ors
      i clones that had been previously isolated from early replicating monkey (CV-1)
      DNA. Autonomous replication was assayed by transient episomal replication in
      transfected HeLa cells; ors-plasmid DNA was isolated at various times after
      transfection and screened by the DpnI resistance assay and the bromodeoxyuridine
      (BrdUrd) substitution assay to differentiate between input and newly replicated
      DNA. Four of the autonomously replicating clones were identified by screening the
      ors-library with probes of ors 3, 8, 9 and 12, previously shown to be capable of
      autonomous replication (Frappier and Zannis-Hadjopoulos, Proc. Natl. Acad. Sci.
      USA (1987) 84, 6668-6672). The other nine functional ors clones were identified
      among 18 randomly chosen ones, which were similarly screened for autonomous
      replication. Nucleotide sequence analyses of 11 of the newly identified
      functional ors plasmids revealed, in most of them, features similar to those
      present in other viral or eukaryotic replication origins, notably the presence of
      AT-rich regions and inverted repeats. Pairwise comparisons between the newly
      identified ors showed no extensive sequence homologies, other than the presence
      of the alpha-satellite repetitive sequence family in three ors and of the
      repetitive Alu sequence family in one ors. The results suggest that there exist
      different classes of mammalian replication origin, highly or moderately
      repetitive and unique, and that their activation is most probably dependent on
      the presence of structural determinants rather than on a particular sequence.

PMID- 2001399
TI  - The cDNA sequence of a neutral horseradish peroxidase.
AB  - A cDNA clone encoding a horseradish (Armoracia rusticana) peroxidase has been
      isolated and characterized. The cDNA contains 1378 nucleotides excluding the
      poly(A) tail and the deduced protein contains 327 amino acids which includes a 28
      amino acid leader sequence. The predicted amino acid sequence is nine amino acids
      shorter than the major isoenzyme belonging to the horseradish peroxidase C group
      (HRP-C) and the sequence shows 53.7% identity with this isoenzyme. The described
      clone encodes nine cysteines of which eight correspond well with the cysteines
      found in HRP-C. Five potential N-glycosylation sites with the general sequence
      Asn-X-Thr/Ser are present in the deduced sequence. Compared to the earlier
      described HRP-C this is three glycosylation sites less. The shorter sequence and
      fewer N-glycosylation sites give the native isoenzyme a molecular weight of
      several thousands less than the horseradish peroxidase C isoenzymes. Comparison
      with the net charge value of HRP-C indicates that the described cDNA clone
      encodes a peroxidase which has either the same or a slightly less basic pI value,
      depending on whether the encoded protein is N-terminally blocked or not. This
      excludes the possibility that HRP-n could belong to either the HRP-A, -D or -E
      groups. The low sequence identity (53.7%) with HRP-C indicates that the described
      clone does not belong to the HRP-C isoenzyme group and comparison of the total
      amino acid composition with the HRP-B group does not place the described clone
      within this isoenzyme group. Our conclusion is that the described cDNA clone
      encodes a neutral horseradish peroxidase which belongs to a new, not earlier
      described, horseradish peroxidase group.

PMID- 2001400
TI  - Quantitative analysis of carbodiimide modified DNA and immunoprobing by adduct
      specific antibodies.
AB  - Antibodies have been raised against N-cyclohexyl-N-(4-methylmorpholinium)ethyl
      carbodiimide (CMC) modified single-stranded DNA and characterized by competitive
      and non-competitive immunoassays to be highly specific for CMC base adduct in
      homopolymers poly(dG), poly(dT) and DNA. The antibodies recognize picogram
      concentrations of CMC treated DNA with no cross reactivity to at least 1000-fold
      excess of unmodified DNA or CMC treated poly(dA). The detection limit of
      antibodies at 1.4 fmol CMC adduct allows quantitation at a CMC/base ratio of
      4.6.10(-7). Based upon single modified base-containing synthetic oligomers, a 7
      fold higher binding preference is observed for CMC modified thymine than guanine
      bases. CMC binding to supercoiled DNA is found to depend upon reaction
      temperature and ionic strength. CMC-modified supercoiled SV40 and ColE1 DNA,
      exhibit specific antibody binding proportional to the DNA concentration and
      extent of CMC modification. However, antibody binding observed is independent of
      the conformation or strandedness of CMC-modified DNA. DNA extensively modified
      with CMC retains its inherent capacity to specifically and quantitatively
      hybridize with complementary DNA immobilized to membranes upon direct blotting or
      Southern transfers from gels. Hybridized CMC-DNA, through antibody binding,
      provides for the sensitive and non-isotopic detection of the target DNA
      sequences.

PMID- 2001401
TI  - Cloning of genomic and complementary DNA encoding insect pheromone binding
      proteins: evidence for microdiversity.
AB  - Genomic DNA from the silk moth Antheraea pernyi bearing the gene of a pheromone
      binding protein has been isolated from a partial genomic library using specific
      cDNA probes. The DNA spans 3.5 kilobases, contains three exons and two
      intervening sequences that interrupt the protein coding region of the gene. A DNA
      fragment of a second gene was isolated and the complete primary structure of a
      corresponding cDNA clone was unravelled. The expression of two different genes,
      giving rise to different pheromone binding proteins, implies a more specific
      function of these proteins than was hitherto assumed.

PMID- 2001402
TI  - Cloning and sequencing of the gene cluster encoding two subunits of membrane
      bound alcohol dehydrogenase from Acetobacter polyoxogenes.
AB  - The membrane-bound alcohol dehydrogenase (ADH) from Acetobacter polyoxogenes
      NBI1028 is composed of a 72 kDa subunit and a 44 kDa cytochrome c subunit. The
      amino acid sequences of the two regions of the 72 kDa subunit were determined to
      prepare oligonucleotides for the purpose of amplification of a DNA fragment
      corresponding to the intermediate region by the polymerase chain reaction. A 0.5
      kb DNA fragment thus amplified was used as the probe to clone a 7.0 kb PstI
      fragment coding for the whole 72 kDa subunit. Nucleotide sequencing and
      immunoblot analysis revealed that the cloned fragment contained the full
      structural genes for the 72 kDa and the 44 kDa subunits and they were clustered
      with the same transcription polarity. The predicted amino acid sequence of the
      gene for the 72 kDa subunit showed homology with that of the 72 kDa subunit from
      ADH of A. aceti and those of methanol dehydrogenase from methylotrophic bacteria.
      The 72 and 44 kDa subunits contained one and three typical haem binding
      sequences, respectively.

PMID- 2001403
TI  - Synthesis of gamma-[4-(benzoylphenyl)methylamido]-7-methylguanosine 5'
      triphosphate, a photoaffinity-label for cap-binding proteins.
AB  - An easy and rapid method for the synthesis of the photoreactive cap analogue
      gamma-[4-(benzoylphenyl)methylamido]-7-methylguanosine-5'-triphosp hate (BP
      m7GTP) has been developed. Synthesis of [gamma-32P]BP-m7GTP was carried out as a
      two-step procedure. The first step included the phosphorylation of GDP with
      [32P]orthophosphate to [gamma-32P]GTP and its methylation to [gamma-32P]m7GTP.
      After purification, [gamma-32P]m7GTP was condensed with 4-aminomethyl
      benzophenone-HCl to [gamma-32P]BP-m7GTP. Using this probe, specific labeling of
      nuclear cap binding proteins is demonstrated.

PMID- 2001404
TI  - Cloning of the cDNA of alpha-momorcharin: a ribosome inactivating protein.
AB  - Using a lambda gt11 cDNA library constructed from the seeds of the bitter melon
      (Momordica charantia), we have obtained a full length cDNA containing the entire
      sequence of alpha-momorcharin by immunoscreening. The length of this cDNA is 1044
      basepairs long and it consists of an open reading frame coding for a polypeptide
      of 286 amino acids. The first 23 residues of this polypeptide probably code for a
      signal sequence. The N-terminal sequence of the deduced protein is exactly
      identical to that determined by peptide sequencing. The sequence identity between
      alpha-momorcharin and other ribosome inactivating proteins, such as trichosanthin
      and ricin A chain, is high, i.e., 34-63%. Examination of the predicted secondary
      structure of alpha-momorcharin and trichosanthin indicates that these proteins
      have regions of high structural similarities and this may account for the common
      biological activities that they share, viz., abortificant, immunosuppressive,
      antitumor and inhibition of HIV-1.

PMID- 2001405
TI  - Cloning and characterization of the carp prolactin gene.
AB  - A carp genomic DNA clone containing the carp prolactin (Prl) gene was isolated
      with carp Prl cDNA as a probe. The organization of the carp Prl gene was
      determined by restriction nuclease mapping and nucleotide sequencing. The Prl
      gene comprises approx. 2.8 kilobasepairs (kb) of DNA including the 5'-flanking
      region, five exons, four introns and the 3'-flanking region. Analysis of the 5'
      flanking region reveals (1) the sequence TATATAAT at positions -38 to -31
      upstream from the cap site which was found to be a guanine residue, and (2) the
      palindrome, CTCATTGCATATACAAATGAG at positions -79 to -59. The carp Prl gene
      matches with the reported cDNA except for one difference in coding region and
      five in the 3'-flanking region, while the encoded amino acid sequences are
      identical. The arrangement of exons and introns is very similar to that seen in
      carp GH as well as mammalian Prl, which, however, have much longer introns.

PMID- 2001406
TI  - cDNA and deduced amino acid sequences of a dog liver cytochrome P-450 of the IIIA
      gene subfamily.
AB  - A 1.96 kbp cDNA encoding a male Beagle dog liver cytochrome P-450 of 503 amino
      acid residues (Mr 57,636) has been isolated and sequenced. The deduced amino acid
      sequence is 79.8%, 69.3% and 74.1% identical to the P450IIIA forms human NF25,
      rat PCN1 and rabbit LM3c, respectively. The amino terminal sequence is identical
      to the first 28 residues of the dog P450IIIA form PBD-1. Southern blot analysis
      yields restriction patterns consistent with IIIA gene subfamily multiplicity.

PMID- 2001407
TI  - Nucleotide sequence of the lipase gene lip3 from the antarctic psychotroph
      Moraxella TA144.
AB  - A lipase gene (lip3) from the psychotrophic strain Moraxella TA144 has been
      cloned and sequenced. The deduced primary structure of the lipase preprotein is
      composed of 315 amino acids with a predicted Mr of 34,772. This enzyme contains
      two consensus peptides showing cluster of glycine residues that may be involved
      in domain flexibility. The cloned gene product conserves the low temperature
      activity and the thermolability properties of the wild enzyme.

PMID- 2001408
TI  - The role of adhesive interactions and extracellular matrix fibronectin from human
      polymorphonuclear leukocytes in the respiratory burst.
AB  - The Arg-Gly-Asp (RGD) tripeptide and ajoene were used for studying the role of
      adhesive receptors in the respiratory burst. Activation of the respiratory burst
      was examined by using luminol-dependent and lucigenin-dependent
      chemiluminescence. Recently, it was shown that ajoene, (E, Z)-4,5,9-trithiadodeca
      1,6,11-trien-9-oxide, a substance isolated from garlic extract, inhibits the
      binding of fibrinogen to activated platelets by direct interaction with
      fibrinogen receptor (Apitz-Castro, R., Lederma, E., Escalante, J. and Jain, M.K.
      (1986) Biochem. Biophys. Res. Commun. 141, 145-150). Taking into consideration
      the structural and functional similarity of integrins, it would be reasonable to
      assume that ajoene as well as RGD can inhibit adhesive interactions of human
      neutrophils. We have shown that the effect of various activators on the
      respiratory burst was abolished by ajoene or RGD treatment. The inhibitory effect
      of RGD and ajoene was dose-dependent. The treatment of neutrophils with antiserum
      against human plasma fibronectin inhibited the respiratory burst in response to
      formyl-methionyl-leucylphenylalanine (fMLP) and phorbol 12-myristate 13-acetate
      (PMA). This effect is dose-dependent and reversible with the addition of
      fibronectin. These data indicate that the respiratory burst in human neutrophils
      is mediated by the integrin family of receptors and that interactions between the
      extracellular matrix fibronectin and cells are necessary for the respiratory
      burst.

PMID- 2001409
TI  - Role of ABH blood group antigens in the stimulation of a DIDS-sensitive Ca2+
      influx pathway in human erythrocytes by Ulex europaeus agglutinin I and a
      monoclonal anti A1 antibody.
AB  - Of eleven agglutinating lectins tested, only one, Ulex europaeus agglutinin I
      (UEA1), stimulated Ca2+ uptake in quin2-loaded erythrocytes by about 2-fold. UEA1
      is known to be an alpha-L-fucose and ABH blood group specific lectin. The 45Ca2+
      influx induced by UEA1 was absent in the presence of extracellular fucose (5 and
      15 mM) and depended on the ABH blood group of the donor, the stimulatory potency
      of the lectin decreasing in the order H greater than A2 greater than A1. Ca2+
      entry blockers, such as cobalt and verapamil, did not affect the 45Ca2+ influx
      induced by UEA1. 4,4'-Diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS)
      inhibited dose-dependently with a Ki of 1-2 microM. 10 microM DIDS, 10 microM
      4,4'-dinitrostilbene-2,2'-disulfonic acid (DNDS) and 20 microM dipyridamole fully
      blocked the 45Ca2+ influx induced by UEA1. The effect of UEA1 on 45Ca2+ influx
      was absent in K+ and Mg2+ media and was less pronounced in choline than in Na+
      media. The 45Ca2+ influx induced by the lectin was abolished by preincubation
      with 12-O-tetradecanoylphorbol 13-acetate (TPA, 60 ng/ml). A monoclonal antibody
      raised against A1 erythrocytes (Bric 54) accelerated 45Ca2+ influx in quin2
      loaded A1 erythrocytes by about 2-fold. No effect was seen in A2 and H
      erythrocytes. The 45Ca2+ influx elicited by Bric 54 exhibited a sensitivity
      towards inhibition by DIDS and TPA, as well as a dependence on the cation
      composition of the incubation medium similar to that observed with UEA1. The
      effects of UEA1 and Bric 54 were not additive. These observations suggest that
      the Ca2+ influx induced by UEA1 and Bric 54 is mediated by the same transport
      pathway. Since both the lectin and the antibody exhibit ABH blood group
      specificity, it appears reasonable to conclude that ABH antigens can serve as
      recognition sites for activation of a Ca2+ influx pathway in human erythrocytes,
      which is sensitive to inhibitors of the band 3 anion-exchanger.

PMID- 2001410
TI  - The isolated neonatal rat-cardiomyocyte used in an in vitro model for 'ischemia'.
      I. A morphological study.
AB  - Cultured heart cells have been recently shown to be useful for analysing states
      of oxygen- and volume-restrictions, conditions that are known to simulate anoxia
      and ischemia at the cellular level. In the present study, we examined the
      ultrastructural damage caused to cultured neonatal rat heart cells when they were
      subjected to simulated ischemia by volume restricted anoxia ('ischemia') in an in
      vitro system. Both thin-sectioning and freeze-fracturing electron microscopy
      revealed a mitochondrial reorganization after 30 min of 'ischemia', whereas
      multilamellar structures could be detected inside the mitochondria after another
      30 min. At this time-point, changes were also observed regarding the organization
      of the sarcolemma. In addition to a slight aggregation of the intramembranous
      particles (IMP's) we found an extensive extrusion of particle-free multilamellar
      membrane-structures, possibly due to a loss of the sarcolemma/cytoskeleton
      interaction. These morphological changes are comparable to those previously
      observed in in vivo and Langendorff studies and the results of the present study
      therefore underline the usefulness of this recently introduced model for
      ischemia.

PMID- 2001411
TI  - The isolated neonatal rat-cardiomyocyte used in an in vitro model for 'ischemia'.
      II. Induction of the 68 kDa heat shock protein.
AB  - In a model system of cultured rat cardiac cells, the expression of the heat shock
      protein hsp68 was studied after simulating ischemia. We observed both an increase
      in hsp68 mRNA levels and hsp68 synthesis, while under normal conditions hsp68 and
      its mRNA could not be detected. Using an antibody against hsp70 and hsp68,
      immunofluorescence studies showed that during 'ischemia', when hsp68 is not yet
      synthesized, hsp70 migrated into the nucleus. These results demonstrate that the
      expression of hsp68 can be used as a marker for the occurrence of ischemia.
      Furthermore, these findings support the fact that this in vitro system is a
      suitable model for the study on myocardial infarction.

PMID- 2001412
TI  - The release of iron and transferrin from the human melanoma cell.
AB  - The role of the transferrin homologue, melanotransferrin (p97), in iron
      metabolism has been studied using the human melanoma cell line, SK-MEL-28, which
      expresses this antigen in high concentrations. The release of iron and
      transferrin were studied after prelabelling cells with human transferrin doubly
      labelled with iron-59 and iodine-125. Approx. 45% of internalised iron was in
      ferritin with little redistribution during reincubation. Iron release was linear
      with time, while transferrin release was biphasic, suggesting that iron was
      leaving the cell independently of transferrin. Unlabelled diferric transferrin
      increased transferrin release, implying a degree of coupling between cell surface
      binding, internalisation and release of transferrin. Increasing the preincubation
      time increased the amount of transferrin which remained internalised within the
      cell. A membrane-bound, iron-binding component with properties consistent with
      melanotransferrin was observed. Desferrioxamine or pyridoxal isonicotinoyl
      hydrazone could not remove iron from this compartment, suggesting a high affinity
      for iron. The number of membrane iron-binding molecules per cell was estimated to
      be 387,000 +/- 7000 . The non-transferrin-bound membrane Fe did not decrease
      during reincubation periods up to 5 h, suggesting that the cell was not utilising
      it. Hence, melanotransferrin may not have a role in internalising iron in
      melanoma cells.

PMID- 2001413
TI  - Characterization of cultured alveolar epithelial cell xanthine
      dehydrogenase/oxidase.
AB  - Conversion of xanthine dehydrogenase (XDH) to xanthine oxidase (XO) and the toxic
      reactions of subsequent XO-derived superoxide, hydrogen peroxide and hydroxyl
      radical, have been suggested to be critical factors in several mechanisms of
      tissue pathophysiology. In the lung, intracellular XO-derived products may
      modulate type II pneumocyte surfactant turnover and barrier function,
      jeopardizing the pulmonary air-blood barrier. We characterized total cellular
      XDH/XO enzymatic activity in freshly isolated and cultured rat pulmonary type II
      epithelial cells. Type II cells were isolated and cultured on fibronectin
      pretreated dishes, with a plating efficiency after 36 h in culture of 40% or 14%
      when quantified via cellular protein or DNA, respectively. Over the subsequent 96
      h in culture, monolayer DNA was unchanged, whereas protein per cell increased
      continuously. Alterations in different cellular enzymatic activities were also
      detected in these cultured cells. In culture, total cellular XDH/XO and catalase
      activities decreased in a logarithmical fashion with respect to time, whether
      normalized for cellular protein or DNA. The rate of loss of these enzymes was
      greatest when normalized for cell protein, but was also significant when the
      activities were normalized for DNA. When compared to freshly isolated type II
      cells, catalase and total XDH/XO activities normalized for protein decreased 78%
      and 72%, respectively, during the first 36 h of culture. After 132 h in culture,
      XDH/XO and catalase activities normalized for protein decreased 93% and 84%,
      respectively, when compared to freshly isolated cell values. Total cellular
      XDH/XO activity in the oxidase form (% XO) was initially 31% in freshly isolated
      type II cells and increased to 67% during the 132 h culture period. In contrast
      to the loss of total cellular XDH/XO and catalase, no significant change in
      lactate dehydrogenase (LDH) activity occurred during culture of the type II
      cells. In type II cells the conversion of XDH to XO, the cytotoxic potential of
      XO, and the activity of the hydrogen peroxide scavenger, catalase, is expected to
      be strongly influenced by in vitro culture. Thus, strong consideration should be
      made before transposing information obtained from cultured type II cells to in
      vivo situations.

PMID- 2001414
TI  - Stimulation of lipid peroxidation increases the intracellular calcium content of
      isolated hepatocytes.
AB  - Lipid peroxidation induced in isolated rat hepatocytes by FeCl3 (0.1 mM) was
      associated with an increase in the cytosolic free Ca2+ and in the ionophore
      mobilizable Ca2+ content of both mitochondrial and extramitochondrial
      (endoplasmic reticular) pools. Ca2+ accumulation was completely prevented by the
      antioxidants promethazine and vitamin E succinate and was not linked to the
      inhibition of plasma membrane (Ca2+ + Mg2+)-ATPase and Ca2+ transport or to the
      depletion of intracellular ATP content. Moreover, preincubation of the
      hepatocytes with the Ca2+ channel blockers verapamil and nifedipine inhibited the
      elevation of cytosolic Ca2+, as well as the ion accumulation without interfering
      with the stimulation of lipid peroxidation by iron. These results suggest that
      peroxidative alterations of the hepatocyte plasma membranes might perturb the
      functions of verapamil- and nifedipine-sensitive Ca2+ channels resulting in a net
      influx of Ca2+, which is subsequently sequestrated in the intracellular
      compartments.

PMID- 2001415
TI  - Iodoacetate action on endocytic uptake of different fluid-phase markers by OK
      renal epithelial cells.
AB  - When grown in monolayer culture, OK cells display endocytic uptake of soluble
      fluid-phase markers such as lucifer yellow (LY) and horseradish peroxidase (HRP).
      The response of this process to metabolic inhibitors was characterized in the
      present study. Inhibition of cell metabolism by cyanide produced a decrease in
      cell ATP content which was accompanied by a decrease in uptake of both LY and
      HRP, confirming the energy-dependence of fluid-phase endocytosis in OK cells. Use
      of iodoacetate also decreased cell ATP content but its action on endocytosis was
      unexpected. Cell uptake of HRP was decreased by iodoacetate, similar to the
      effect of cyanide, but there was a marked increase in LY uptake. Additional
      studies showed that cyanide did not change intracellular Na+ or intracellular K+
      and did not interfere with the Na(+)-dependency of Pi uptake. In contrast,
      iodoacetate produced a marked increase in Na+, a decrease in K+, and abolished
      the Na(+)-dependency of Pi transport. The latter was due primarily to a 10-fold
      increase in Na(+)-independent uptake of Pi. These findings suggest, indirectly,
      that plasma membrane permeability to Na+, K+, Pi, and small molecules such as LY,
      may be increased by iodoacetate, possibly through its action as an alkylating
      agent. This mechanism may allow increased cell uptake of LY through a non
      endocytic pathway, and may mask the inhibitory action of iodoacetate on endocytic
      uptake of LY. These additional effects complicate the use of iodoacetate to
      interrupt endocytosis.

PMID- 2001416
TI  - Platelet activating factors (AGEPC) from epidermal secretions of the Arabian Gulf
      catfish, Arius bilineatus, which stimulate wound healing.
AB  - High levels of platelet activating factor (PAF) activity were demonstrated by
      platelet aggregation and serotonin release assays to be present in fright induced
      epidermal secretions of the Arabian Gulf catfish, Arius bilineatus (Valenciennes,
      1840). The PAF activity was purified by thin-layer chromatography. Mass spectral
      analysis combined with chemical and enzymatic modification of the purified PAF
      and inhibitor studies indicated that PAF activity was due to the presence of 1-O
      alkyl-2-acetyl-sn-glycero-3-phosphorylcholine (AGEPC) molecules. The total AGEPC
      concentration in the epidermal secretions based on PAF assays was 8 x 10(8) M,
      well above the threshold level for platelet activation which is near 5 x 10(-11)
      M. Thus, stimulated epidermal secretory cells of Arius bilineatus supply platelet
      activating molecules at physiologically high concentrations to sites of injury.

PMID- 2001417
TI  - Hepatocellular uptake of peptides by bile acid transporters: relationship of
      carrier-mediated transport of linear peptides with renin-inhibiting activity to
      multispecific bile acid carriers.
AB  - The uptake of a linear peptide with renin-inhibiting activity (code number EMD
      51921) was characterized in isolated rat liver cells. Isolated hepatocytes take
      up EMD 51921 in a time-, concentration-, energy- and temperature-dependent
      manner. Transport of the peptide follows mixed-type kinetics. Diffusion occurs at
      a rate of 8.123 x 10(-6) cm/sec at 6 degrees C. For the saturable part of uptake,
      a Km of 2.0 microM and a Vmax of 160 pmol/mg per min were calculated. Various
      substrate analogues inhibit the uptake of EMD 51921. Absence of oxygen or
      decreased cellular ATP content (e.g., by metabolic inhibitors or xylulose) blocks
      hepatocellular uptake of EMD 51921. Temperatures above 20 degrees C accelerate
      the uptake. The activation energy was calculated to be 58.3 kJ/mol. The
      apparently active uptake of EMD 51921 was not sodium dependent. The membrane
      potential is a driving force for the accumulation of EMD 51921. Mutual
      competitive transport inhibition of EMD 51921, cholate and taurocholate is
      indicative of a common transport system. Benzamidotaurocholate and a
      cyclosomatostatin analog 008, not phalloidin and iodipamide, however,
      considerably decrease the uptake of EMD 51921. AS 30D ascites hepatoma cells,
      unable to accumulate bile acids and certain cyclopeptides, also fail to transport
      EMD 51921. BSP, a foreign substrate of the bilirubin carrier, noncompetitively
      inhibits the transport of EMD 51921. The inhibition of the uptake of EMD 51921 by
      rifampicin, a further substrate of the bilirubin carrier, is mixed: competitive
      at high EMD 51921 concentrations and uncompetitive at low EMD 51921
      concentrations. The uptake of rifampicin into isolated rat liver cells, however,
      is not influenced by EMD 51921. Substrates of the transport systems for cations,
      amino acids, long chain fatty acids and hexoses did not influence the transport
      of EMD 51921.

PMID- 2001418
TI  - Tumor necrosis factor-alpha stimulates phosphatidylinositol breakdown by
      phospholipase C to coordinately increase the levels of diacylglycerol, free
      arachidonic acid and prostaglandins in an osteoblast (MC3T3-E1) cell line.
AB  - The effects of (human recombinant) tumor necrosis factor-alpha on
      phosphatidylinositol breakdown, release of 1,2-diacylglycerols, mobilization of
      arachidonate from diacylglycerol and prostaglandin synthesis were examined in a
      model osteoblast cell line (MC3T3-E1). Tumor necrosis factor-alpha (10 nM) caused
      a specific (30%) decrease in the mass of phosphatidylinositol (and no other
      phospholipids) within 30 min of exposure. Tumor necrosis factor-alpha doubled the
      rate of incorporation of [32P]orthophosphoric acid into phosphatidylinositol,
      indicating that the turnover of inositol phosphate was enhanced, and increased
      the content of diacylglycerol in parallel with phosphatidylinositol breakdown.
      The cytokine (10-50 nM; 4 h) also promoted a specific release of 24-34% of the
      [3H]arachidonate from prelabeled phosphatidylinositol, a release of 80% of the 3H
      fatty acid from the diacylglycerol pool, and a 30-fold increase in the synthesis
      of prostaglandin E2. The tumor necrosis factor-alpha induced liberation of
      [3H]arachidonate from diacylglycerol, cellular arachidonate release and the
      synthesis of prostaglandin E2 were each blocked by an inhibitor of diacylglycerol
      lipase, the compound RHC 80267 (30 microM). Therefore, we conclude that, in the
      MC3T3-E1 cell line, tumor necrosis factor-alpha activates a phosphatidylinositol
      specific phospholipase C (phosphatidylinositol inositolphosphohydrolase; EC
      3.1.4.3) to release diacylglycerol, and increases the metabolism of
      diacylglycerol to liberate arachidonate for prostaglandin synthesis.

PMID- 2001419
TI  - Arachidonic acid release by basophilic leukemia cells and macrophages stimulated
      by Ca2+ ionophores, antigen and diacylglycerol: essential role for protein kinase
      C and prevention by glucocorticosteroids.
AB  - The role of protein kinase C in phospholipase A2 (PLA2) activation in rat
      basophilic leukemia cells (RBL-2H3) and macrophages was investigated. 12-O
      Tetradecanoyl phorbol 13-acetate (TPA) doubled ionomycin-induced PLA2 activity,
      assessed by [3H]arachidonate release. Protein kinase C inhibitors, staurosporine
      and K252a (100 nM) or H-7 (15 micrograms/ml) inhibited ionomycin-stimulation of
      PLA2 activity by 62, 75 and 80%, respectively. Down-regulation of protein kinase
      C by prolonged treatment with TPA inhibited Ca2(+)-ionophore A23187 or antigen
      stimulation of [3H]arachidonate release by 80%. We examined whether the
      inhibitory effect of dexamethasone (DEX) on PLA2 activity is related to
      modulation of protein kinase C activity. The 50% inhibition by DEX of ionomycin
      elevation of [3H]arachidonate release was almost overcome by addition of TPA. The
      Ca2+ ionophore and antigen-induced increase in [3H]TPA binding to intact RBL
      cells was not impaired by DEX. However, DEX markedly reduced phosphorylation of
      several proteins. 1-Oleoyl-2-acetyl-glycerol (OAG) had a sustained stimulatory
      effect on PLA2 activity in isolated plasma membranes derived from treated bone
      marrow intact mouse macrophages, while both DEX and staurosporine reduced
      elevated PLA2 activity by 68 and 84%, respectively. The results support an
      essential role for protein kinase C in regulation of PLA2 activity.

PMID- 2001420
TI  - Volatile anesthetics stimulate the phorbol ester evoked neurotransmitter release
      from PC12 cells through an increase of the cytoplasmic Ca2+ ion concentration.
AB  - PC12 cells preloaded with [3H]norepinephrine release this neurotransmitter at a
      slow rate (basal release). This rate is increased by the addition of phorbol
      myristate acetate (PMA), but not by a biologically inactive phorbol ester. This
      effect most likely is mediated by protein kinase C, since desensitization of this
      kinase abolished the stimulation of the neurotransmitter release by PMA.
      Unexpectedly, clinical concentrations of the volatile anesthetics halothane,
      enflurane, isoflurane and methoxyflurane stimulated the PMA evoked
      neurotransmitter release in good correlation with their anesthetic potency. Since
      the volatile anesthetics increased the cytoplasmic Ca2+ concentration of the PC12
      cells in a dose dependent manner it seems very likely that the effect of the
      anesthetics on the PMA-evoked neurotransmitter release is mediated by this rise
      in Ca2+ concentration.

PMID- 2001421
TI  - Tumor necrosis factor (TNF) inhibits interleukin (IL)-1 and/or IL-6 stimulated
      synthesis of C-reactive protein (CRP) and serum amyloid A (SAA) in primary
      cultures of human hepatocytes.
AB  - Interleukin (IL)-1, IL-6 and tumor necrosis factor (TNF) are considered as
      important mediators for the modulation of liver synthesis of acute phase
      proteins. However, studies of the direct effect of individual or a combination of
      these cytokines on the synthesis of acute phase proteins in human hepatocytes are
      still very limited. In this study, we have examined the synthesis of C-reactive
      protein (CRP) and serum amyloid A (SAA) in primary cultures of human hepatocytes
      exposed to recombinant(r)IL-1 alpha (100 U/ml), rIL-6 (2000 U/ml), rTNF alpha (30
      U/ml) and to various combinations of these cytokines in the presence of 1 microM
      dexamethasone. Monoclonal antibodies to rTNF alpha and monospecific anti-rIL-6
      sheep antiserum were also used to investigate the possible endogenous production
      of TNF or IL-6. The findings indicate: (1) IL-1 and IL-6 are stimulatory
      cytokines for the liver synthesis of CRP and SAA. Anti IL-6 abolishes the
      stimulatory effect of IL-1. These findings support the previous observation and
      indicate that IL-1 exerts its action on the enhanced synthesis of CRP and SAA at
      least in part via IL-6 production in the liver cell. (2) TNF is an inhibitory
      cytokine for the liver synthesis of CRP. It inhibits also the stimulatory effect
      of IL-1 and IL-6 on the synthesis of CRP and SAA. (3) Since anti-TNF enhances the
      stimulatory effect of IL-6 on the synthesis of CRP and SAA, it seems likely that
      TNF is also produced by the human hepatocytes. However, further studies for more
      direct evidence of the liver cell production of TNF, such as the detection of TNF
      messenger RNA are required.

PMID- 2001422
TI  - Interactions between inositol phosphates and cytosolic free calcium following
      bradykinin stimulation in cultured human skin fibroblasts.
AB  - The inositol triphosphate (IP3) that results from hydrolysis of
      phosphatidylinositol 4,5-bisphosphate (PIP2) is generally accepted to be
      responsible for the mobilization of intracellular calcium. However, some studies
      suggest that low concentrations of agonists elevate cytosolic free calcium
      concentration ([Ca2+]i) without IP3 formation. Thus, in the present studies, a
      comparison of the temporal response of inositol phosphates (IP3, IP2 and IP) and
      [Ca2+]i to a wide range of bradykinin concentrations was used to examine the
      relation of these two signal transduction events in cultured human skin
      fibroblasts (GM3652). In addition, the effects of alterations in internal or
      external calcium on the response of these second messengers to bradykinin were
      determined. Bradykinin stimulated accumulation of inositol phosphates and a rise
      of [Ca2+]i in a time- and dose-dependent manner. Decreasing the bradykinin
      concentration from 1 microM to 0.1 microM increased the time until the IP3 peak,
      and when the bradykinin concentration was reduced to 0.01 microM IP3 was not
      detected. [Ca2+]i was examined under parallel conditions. As the bradykinin
      concentration was reduced from 1 microM to 0.01 microM, the time to reach the
      peak of [Ca2+]i increased progressively, but the magnitude of the peak was
      unaltered. These two second messengers were variably dependent on external
      calcium. Although the bradykinin-stimulated initial spike of [Ca2+]i did not
      depend on extracellular calcium, the subsequent sustained levels of [Ca2+]i were
      abolished in calcium free medium. The bradykinin-stimulated inositol phosphate
      formation was not dependent on the extracellular calcium nor on the elevation of
      [Ca2+]i that was produced with Br-A23187. These results demonstrate that
      bradykinin-induced IP3 formation can be independent of [Ca2+]i and of external
      calcium, whereas changes in [Ca2+]i are partially dependent on external calcium.

PMID- 2001423
TI  - Osmotic strength differentiates between two types of calcium transport pathways
      regulating catecholamine secretion from cultured bovine chromaffin cells.
AB  - Calcium transport and catecholamine secretion was measured in cultured bovine
      chromaffin cells. Calcium ions which entered the cells following stimulation with
      either nicotine or 50 mM KCl (high potassium) triggered catecholamine release,
      but then inactivated the secretory process. The nicotine and the high potassium
      induced calcium transport mechanisms were mechanistically distinct, but
      functionally dependent on each other. The specific evidence is that whereas the
      high potassium-induced Ca2+ influx was found to be inhibited by hyperosmotic
      medium, the nicotine-stimulated calcium influx was unaffected under these
      conditions. High potassium and nicotine-stimulated catecholamine release were
      also differently affected by hyperosmotic medium. While potassium-stimulated
      catecholamine release was profoundly inhibited by hyperosmolarity, nicotine
      stimulated release was only moderately inhibited. Sequential treatments of cells
      with nicotine and high potassium, under isotonic physiological conditions,
      indicate that there is a functional, biochemical communication between the
      otherwise mechanistically distinct calcium channels. Calcium ions which were
      found to inactivate these channels may be the basis for such communication.

PMID- 2001424
TI  - Nuclear magnetic resonance studies of blood plasma and urine from subjects with
      chronic renal failure: identification of trimethylamine-N-oxide.
AB  - We have used 1H-, 13C- and 14N-NMR spectroscopy to investigate the constituents
      of plasma and urine in 16 patients with chronic renal failure (CRF). Resonances
      not previously observed in spectra of plasma from healthy volunteers were seen in
      CRF plasma, including those for trimethylamine-N-oxide (TMAO) and dimethylamine
      (DMA). A possible analogy with the plasma of elasmobranch fishes, in which TMAO
      stabilizes proteins in the presence of very high urea concentrations, is noted.
      The intensity of the TMAO resonance for CRF subjects was correlated with the
      plasma concentration of urea (R = 0.55) and creatinine (R = 0.74), suggesting
      that the presence of TMAO is closely related to the degree of renal failure. When
      normal subjects ate a meal of TMAO-containing fish, TMAO appeared rapidly in the
      plasma and in the urine. Thus TMAO is efficiently cleared by the healthy kidney.
      Differences in the interaction of lactate with plasma proteins were detected by
      NMR, suggesting that uraemia impairs their transport roles.

PMID- 2001425
TI  - Development of fluorescence and cross-links in eye lens crystallin by interaction
      with lipid peroxy radicals.
AB  - Senile nuclear cataract formation is associated with the accumulation of
      fluorescent insoluble proteins. alpha-Crystallin from bovine eye lens was treated
      with the lipid peroxy radicals generated by interaction of linoleic acid 13
      monohydroperoxide or phosphatidylcholine hydroperoxide with methemoglobin. A blue
      non-tryptophan fluorescence composed of at least two kinds of fluorophores,
      stable and unstable on borohydride treatment, was produced. One of the stable
      fluorophores was identified as dityrosine by comparison of its retention times in
      amino acid analysis and HPLC with those of authentic dityrosine. Dityrosine was
      formed by the radical reaction, and less than 0.3% of the total tyrosine residues
      of the protein were transformed into dityrosine. The unstable fluorophores may be
      produced on the amino groups of alpha-crystallin by the non-radical reaction of
      the decomposition products of the radicals including monofunctional aldehyde
      species. Extensive intermolecular cross-links could not be explained only by the
      dityrosine content, but by the other modifications. Formation of fluorescence and
      intermolecular cross-links in alpha-crystalline in reaction with the lipid peroxy
      radicals suggested the participation of lipid peroxidation in the cataractous
      process.

PMID- 2001426
TI  - Energy status of cells lacking dystrophin: an in vivo/in vitro study of mdx mouse
      skeletal muscle.
AB  - Although great strides have been made in understanding the genetics of Duchenne
      muscular dystrophy (DMD), uncertainty still remains as to the metabolic changes
      which are associated with the disease. We have used the recently discovered
      animal model of DMD, the mdx mouse, to study aspects of high energy phosphate
      metabolism and metabolic control indices in dystrophic muscle. This model of DMD
      has the dual advantage of having a genetic defect which is homologous to that in
      human DMD, and it lacks the fatty infiltration and necrosis which makes
      biochemical analysis of DMD so difficult. We have used nuclear magnetic resonance
      spectroscopy (NMR) to monitor developmental changes in high energy phosphates and
      pH. No differences were observed between young (less than 40-50 days old) control
      and mdx mice. The pH increase and alterations in phosphate ratios (i.e., a
      decline in PCr/ATP) observed in adult mdx vs. control mice are qualitatively
      similar to those observed in humans. Biochemical analysis showed a small decline
      in ATP and PCr content and a decline in some indices of energy status in adult
      mdx mice. As young mdx mice appeared to be normal, the lack of dystrophin does
      not correlate with metabolic changes. The changes which were observed were small
      enough that alterations in fibre composition could be the major contributory
      factor.

PMID- 2001427
TI  - Changes in fibronectin staining in the human lens during ageing and
      cataractogenesis.
AB  - The content and localization of fibronectin, an extracellular glycoprotein, in
      the serial sections of lenses of normal human donors and cataractous patients of
      different ages were determined by the indirect immunoperoxidase staining
      technique. This was followed by the evaluation with quantitative morphometric
      analysis. It was shown that fibronectin was present in the area of cell contacts
      as single deposits of faint orange-brown stained material in the lens samples of
      young donors. The fibronectin level was raised in lens sections from aged donors.
      Its accumulation was detected mostly within the spaces of the lens fiber cells.
      At different stages of cataractogenesis a dramatic decrease of the fibronectin
      content was detected in the lens sections obtained from patients of different
      ages. A new linear spectrophotometric technique was developed for evaluation of
      the lens transparency, to correlate the lens opacity with corresponding
      histological data obtained from the immunostaining technique. Morphological
      studies performed further suggested that the lens fiber cell plasma membrane
      structures were deteriorated. This was observed as changes of fibronectin
      staining in the lens sections at different periods of human ageing and cataract
      development. It is concluded that a decrease of fibronectin staining in the human
      lens is an indication for the structural damage of the lens fiber cell plasma
      membranes during ageing and cataractogenesis.

PMID- 2001428
TI  - Skin-derived antileukoproteinase (SKALP), an elastase inhibitor from human
      keratinocytes. Purification and biochemical properties.
AB  - Recently we reported a preliminary characterization of anti-elastase activity
      which is found in cultured keratinocytes and in epidermis from psoriasis
      patients, but not in normal human epidermis. Here we present evidence that this
      inhibitory activity is derived from a cationic protein with a molecular mass of
      18 kDa. In psoriatic scales the inhibitor is mainly present as a biologically
      active 11 kDa fragment. Inhibition of human leukocyte elastase is strong (Ki = 2
      x 10(11) M) and fast (kon = 10(7) M-1.s-1). Using chromatofocusing, affinity
      chromatography and gel-permeation FPLC, the 11 kDa fragment was purified from
      psoriatic scales. This preparation was reduced and carboxymethylated, blotted
      onto poly(vinylidene difluoride) membrane and subjected to N-terminal gas-phase
      sequencing. Within a stretch of 16 amino acids a 40% homology was found with the
      active site of antileukoproteinase (ALP) a known serine proteinase inhibitor
      present in mucous secretions. We therefore propose the acronym SKALP (skin
      derived antileukoproteinase) as a name for this elastase inhibitor.

PMID- 2001429
TI  - Lipid peroxide and transition metals are required for the toxicity of oxidized
      low density lipoprotein to cultured endothelial cells.
AB  - The toxicity of oxidized low density lipoprotein (Ox-LDL) to cultured vascular
      endothelial cells was investigated. The modification of low density lipoprotein
      (LDL) by copper led to the production of thiobarbituric acid-reacting substance
      (TBARS) and lipid hydroperoxide (LPO). TBARS was distributed not only in
      lipoprotein, but also in the aqueous phase, whereas LPO was observed only in the
      lipoprotein particle. During the incubation of LDL with copper, the copper bound
      to lipoprotein and formed a complex. The toxicity of products resulting from the
      oxidation of LDL to endothelial cells was recognized in Ox-LDL particles, not in
      the aqueous phase. Following dialysis of Ox-LDL against EDTA, copper which had
      bound to the Ox-LDL particle was released and the toxicity of Ox-LDL disappeared.
      The addition of copper to the dialyzed Ox-LDL restored the cytotoxicity. To a
      lesser extent this effect was also observed with the addition of iron. A study of
      the time-course of LDL oxidation showed that the toxicity of Ox-LDL depends upon
      the level of LPO, not upon the content of TBARS, the extent of negative charge or
      the protein adduct of aldehydes. These results demonstrate that transition metal
      is required for Ox-LDL toxicity and that the toxic moiety of the products
      resulting from LDL oxidation is LPO associated with the Ox-LDL particle.

PMID- 2001430
TI  - Neutral lipid storage disease: a possible functional defect in phospholipid-
      linked triacylglycerol metabolism.
AB  - Neutral lipid storage disease (NLSD) (Chanarin-Dorfman Syndrome) is an autosomal
      recessive disorder of multisystem triacylglycerol (TAG) storage. Previous work
      has pointed to a defect in intracellular TAG metabolism. In the studies reported
      here, the lipid metabolism of three lines of NLSD fibroblasts were compared to
      normal skin fibroblasts. When pulsed with [3H]oleic acid, the earliest observed
      abnormality in NLSD cell lines was increased incorporation into
      phosphatidylethanolamine, followed by accumulation of radiolabel in TAG.
      Activities of several glycerolipid synthetic enzymes were comparable in NLSD and
      normal fibroblast lines, excluding oversynthesis of glycerolipid. The proportion
      of plasmalogen and neutral ether lipid synthesized was normal and alkylglycerols
      did not accumulate, excluding a defect in ether lipid metabolism. Activities of
      both acid lipase and Mn2(+)-sensitive lipase within the particulate fractions of
      NLSD and normal fibroblasts were comparable. These studies are most consistent
      with functional deficiency of a TAG lipase with activity against a pool of TAG
      that are normally utilized for phospholipid biosynthesis.

PMID- 2001431
TI  - Progestin stimulation of thymidine kinase in the human breast cancer cell line
      T47D.
AB  - Our laboratory has previously reported that progestins stimulate growth of the
      human breast cancer cell line T47D. In an attempt to probe further into this
      stimulation, we are investigating progestin effects on thymidine kinase (EC
      2.7.1.21), an enzyme known to be involved in growth regulation. This report
      relates our finding that progestins stimulate thymidine kinase activity, at
      physiological progestin concentrations, in a dose-responsive manner. Estradiol-17
      beta also stimulates, but testosterone, hydrocortisone and aldosterone do not.
      The antiprogestin RU486 inhibits progestin stimulation, but also stimulates on
      its own. Maximal by 24 h, the progestin stimulation then falls off with time.
      Experiments with actinomycin D and cycloheximide suggest that the thymidine
      kinase stimulation depends on new RNA and protein synthesis. These data shed
      further light on progestin stimulation of the growth of human breast cancer. To
      our knowledge, this is the first report of progestin stimulation of thymidine
      kinase in human breast cancer cells.

PMID- 2001433
TI  - Testimony to an abiding faith.

PMID- 2001432
TI  - Identification of 'cystic fibrosis protein' as a complex of two calcium-binding
      proteins present in human cells of myeloid origin.
AB  - Cystic fibrosis protein is a serum protein characterized by a pI close to 8.4 and
      present with a higher concentration in serum and plasma of cystic fibrosis
      carriers than in controls. This protein was found immunologically
      indistinguishable from the cystic fibrosis antigen isolated from granulocytes and
      presenting a sequence analogous to that of MRP-8, a calcium-binding protein
      expressed in the myeloid cell lineage. Using antibodies directed against MRP-8
      and its closely associated calcium-binding protein, MRP-14, we demonstrate here
      that cystic fibrosis protein purified from serum is a complex of the two proteins
      MRP-8 and MRP-14.

PMID- 2001434
TI  - House of delegates action on resolutions.

PMID- 2001435
TI  - In vitro fertilization: effective alternative to surgery for distal tubal
      occlusion.
AB  - A total of 512 consecutive patients with tubal infertility underwent ovarian
      hyperstimulation for the purpose of IVF-ET, resulting in a total of 829 attempts
      and 890 transfers (fresh and cryo). Overall, 218 clinical pregnancies were
      achieved, of which 114 (52.3%) resulted in live births, and 38 (17.4%) were
      ongoing (greater than or equal to 20 weeks of gestation) at the conclusion of the
      study. The total live birth and ongoing pregnancy rate per patient was 29.7%
      (three patients conceived twice). The probability for a patient to achieve a live
      or ongoing pregnancy was 42.7% after three attempts and 85.3% after six attempts.
      We conclude that IVF-ET using contemporary technology offers an effective
      alternative to surgery for tubal obstruction.

PMID- 2001436
TI  - Primary care and the asymptomatic HIV patient.
AB  - Most patients with HIV infections are asymptomatic or minimally symptomatic.
      Primary care physicians can play a unique and vital role in their care. They
      should: 1. Look for cases. Treatment can prevent or delay progression of disease.
      2. Know how to interpret the serologic tests for HIV infection. 3. Collect an
      adequate data base to assess extent and severity of disease and screen for
      certain coexisting infections. 4. Intervene appropriately with counseling and
      prophylactic therapy. 5. Refer early when neoplasia, opportunistic infections, or
      diagnostic uncertainties occur.

PMID- 2001437
TI  - Chronic fever and lymphadenopathy.

PMID- 2001438
TI  - In the wake of Cruzan. In Virginia, two routes to clear and convincing evidence.

PMID- 2001439
TI  - Professional courtesy.

PMID- 2001440
TI  - He likes idea of return to medical school for CME.

PMID- 2001441
TI  - Professional courtesy defrauds, say health insurers.

PMID- 2001442
TI  - Two see need for change in Va Med Q's focus.

PMID- 2001443
TI  - Neurodevelopmental aspects of bipolar affective disorder.

PMID- 2001444
TI  - Phenylethylaminergic mechanisms in attention-deficit disorder.
AB  - Urinary excretion (24-hr) of beta-phenylethylamine (PEA), phenylacetic acid
      (PAA), phenylalanine (Phe), and p-tyrosine (Tyr), and plasma levels of PAA, Phe,
      and Tyr were examined in 18 normal children and 26 children diagnosed as having
      attention-deficit hyperactivity disorder (ADHD). The results indicated that
      urinary excretion (expressed per g of creatinine) of free and total PEA was
      significantly lower in the ADHD patients, and plasma levels of Phe and Tyr were
      also decreased in the ADHD subjects compared with the normal controls.

PMID- 2001445
TI  - Acute effect of intravenous clomipramine upon sleep-related hormone secretion in
      depressed outpatients and healthy control subjects.
AB  - Tricyclic antidepressants have been used frequently as pharmacological probes in
      neuroendocrine studies even though they appear to lack neurochemical specificity.
      Despite this, the hormonal responses to these drugs have been used to provide
      evidence that depressed patients have alterations in both noradrenergic and
      serotonergic tone within the central nervous system. Most studies have been
      conducted in the morning, which is not a time of high physiological
      neuroendocrine secretory activity. The present study has used the relatively
      specific serotonergic probe intravenous clomipramine given to depressed patients
      and healthy subjects immediately before sleep onset, which is a time of increased
      neuroendocrine activity. Under these conditions, 12.5 mg clomipramine stimulates
      the secretion of both cortisol and prolactin, but unlike studies conducted in the
      morning, clomipramine suppresses the secretion of growth hormone in both groups.
      These data suggest that serotonergic mechanisms are involved in the regulation of
      the secretion of these three hormones at the time of sleep onset.

PMID- 2001446
TI  - Cerebral structure on MRI, Part I: Localization of age-related changes.
AB  - In this report, earlier findings of age-related changes in brain morphology on
      magnetic resonance (MR) images are extended to include measurements of individual
      cerebral grey matter structures and an index of white matter degeneration.
      Volumes of caudate, lenticular, and diencephalic structures are estimated, as are
      grey matter volumes in eight separate cortical regions. Results suggest that
      between 30 and 79 years significant decreases occur in the volume of the caudate
      nucleus, in anterior diencephalic structures, and in the grey matter of most
      cortical regions. The data suggest that the volumes of the thalamus and the
      anterior cingulate cortex may be unchanged. Among those cortical regions found to
      be affected in aging, some evidence is present for greater change in association
      cortices and mesial temporal lobe structures. There are also dramatic age-related
      changes in the white matter, manifest as lengthened T2 values on MR images.

PMID- 2001447
TI  - Tobacco smoking increases square-wave jerks during pursuit eye movements.
AB  - Smooth-pursuit eye-movement (SPEM) abnormalities have been consistently observed
      in schizophrenia. The SPEM changes in schizophrenia are not thought to be an
      artifact of voluntary attention or medication, although a number of nondisease
      factors are known to affect SPEM. However, cigarette smoking has recently been
      reported to deteriorate SPEM in both smokers and nonsmokers. This finding is
      particularly relevant to schizophrenia, because schizophrenic patients smoke
      cigarettes considerably more than do normals, and none of the previous studies in
      this patient group have controlled for smoking. The current study was initiated
      to examine the effects of smoking on a number of oculomotor measures, including
      SPEM in smoker and nonsmoker normal volunteers. The results of this study suggest
      that cigarette smoking induces or significantly increases square-wave jerks,
      especially during smooth pursuit in normals. However, the effect is small and the
      global qualitative SPEM score is not affected. Other eye movements such as
      latencies for reflex and volitional saccades and saccadic distractibility are
      also unaffected by smoking. No differences were apparent between chronic smokers
      and nonsmokers under nonsmoking conditions in any of the eye-movement measures.

PMID- 2001448
TI  - Molecular physiology of granulocyte-macrophage colony-stimulating factor.

PMID- 2001449
TI  - The effect of 5-fluorouracil on erythropoiesis.
AB  - The effects of a single dose (150 mg/kg) of 5-fluorouracil on mature erythroid
      and erythropoietic and multipotential in vitro precursor populations in the bone
      marrow and spleen and circulating biologically (erythroid colony forming unit
      [CFU-E] assay) and immunologically active (enzyme-linked immunosorbent assay)
      erythropoietin (Epo) are described. All mature erythroid (reticulocytes,
      erythrocytes) and in vitro erythropoietic precursors (CFU-E, erythroid burst
      forming unit [BFU-E]) are severely reduced, if not eradicated. Transient
      repopulation of the pure BFU-E and CFU-E populations on days 6 and 7,
      respectively, produces a marked reticulocytosis after day 9. Circulating Epo
      increases to above normal values by day 2. However, whereas biologically active
      Epo remains constant at this level until day 9, immunologically active Epo
      continually increases; by day 12, however, both assays detect circulating Epo
      levels of about 400 mU/mL. In vitro multipotential stem cells (BFU-E mix) are
      reduced to 32% on day 1, 7.6% on day 2, and return to normal values between days
      4 and 5. The survival and repopulation kinetics of the BFU-E mix imply a stem
      cell population more mature than the high proliferative potential colony-forming
      cells. However, the BFU-E mix may be responsible for erythropoiesis repopulating
      ability.

PMID- 2001450
TI  - Human interleukin-3 mRNA accumulation is controlled at both the transcriptional
      and posttranscriptional level.
AB  - Interleukin-3 (IL-3) is a hematopoietic growth factor that regulates the
      differentiation of multilineage and committed progenitor cells and the functions
      of some mature blood cells. The expression of human IL-3 appears to be restricted
      to stimulated T lymphocytes. We have investigated the kinetics and mechanisms
      involved in the induction of IL-3 expression in the human T lymphocytic tumor
      cell line Jurkat. We show that accumulation of IL-3 mRNA is controlled at both
      the transcriptional and posttranscriptional level. Transcription of the IL-3 gene
      in these cells appears to be constitutive but no IL-3 mRNA was detected in
      unstimulated cells, indicating that in resting cells IL-3 mRNA is highly
      unstable. Treatment with phytohemagglutinin (PHA) induced a small and transient
      increase in the IL-3 gene transcription rate and led to the production of
      detectable levels of IL-3 mRNA and protein. Optimal induction of IL-3 expression
      required a second stimulus. Costimulation of Jurkat cells with both phorbol
      myristate acetate and PHA caused both a transient increase in IL-3 gene
      transcription, which is dependent on new protein synthesis, and also a transient
      increase in mRNA stability.

PMID- 2001451
TI  - Continued blood cell formation in spherical bodies in a long-term mouse spleen
      culture.
AB  - During the primary culture of spleen fragments of newborn mice, a spherical body
      (d = circa 200 to 300 microns) as a three-dimensional cellular organization was
      formed. Continued production of blood cells from the spherical body was observed
      without changing its size for about 2 months of culture. Without growth factor,
      the spherical bodies produced mainly lymphocytes and macrophages. Addition of
      interleukin-3 enhanced their granulocyte formation, and this enhancement was
      observed even after a prolonged maintenance without growth factors. The spherical
      bodies were composed of a uniform mixture of endothelial cells and fibroblasts
      within the body, and cell-cell contacts between lymphocytes and fibroblasts were
      notable in the periphery. With prolonged culture, the spherical bodies showed a
      definite change in their structure by sorting two cell types and the blood cell
      production gradually decreased. These results suggested that a three-dimensional
      structure was required for the maintenance, growth, and differentiation of blood
      cell progenitors in the long-term spleen culture.

PMID- 2001452
TI  - Induction of protein kinase C mRNA in cultured lymphoblastoid T cells by iron
      transferrin but not by soluble iron.
AB  - Iron-transferrin (FeTF) is an essential growth factor required for proliferation
      of lymphoid cells. FeTF activates protein kinase C (PKC) in the lymphoblastoid T
      cell line, CCRF-CEM. We have treated CEM cells with human FeTF, then examined
      levels of PKC mRNA by hybridization analysis using cDNA probes specific for alpha
      , beta-, and gamma-PKC subspecies. CEM cell mRNA hybridized with the beta
      subspecies probe but not with probes for alpha- or gamma-subspecies. After
      exposure to FeTF an increase in PKC-beta mRNA was detectable at 10 minutes,
      peaked at 12 hours, and was sustained for 72 hours. Nuclear transcription assays
      demonstrated that rates of PKC-beta mRNA transcription were increased in FeTF
      treated cells. By contrast, steady state levels of PKC-beta mRNA did not increase
      after treatment of cells with apotransferrin or gallium TF. Similarly, treatment
      with soluble iron as ferric ammonium citrate did not increase steady state levels
      of PKC-beta mRNA, despite producing a marked increase in cellular ferritin
      content. Ferritin increased from a baseline value of 63 ng/10(6) cells to 98 and
      100 ng/10(6) cells in CEM cells treated for 1 hour with ferric ammonium citrate
      or FeTF, respectively. FeTF did not increase cytoplasmic-free calcium in CEM
      cells loaded with fura-2, indicating that binding of FeTF to transferrin
      receptors did not open membrane Ca2+ channels or release intracellular Ca2+. In
      addition, pretreatment of cells with desferrioxamine, but not ferrioxamine,
      blocked the FeTF-induced increase in PKC-beta transcripts. Therefore, iron as
      FeTF (not soluble iron or nonferric TF) stimulates transcription of the CEM cell
      PKC-beta gene. Transcriptional rate of the PKC-beta gene does not correlate with
      cellular iron content as judged by ferritin measurements. Furthermore, the
      requirement for FeTF does not appear to reflect activation of a classic agonist
      pathway as judged by stable cellular Ca2+. These data suggest that delivery of
      iron by FeTF to one or more specific cellular compartments may stimulate PKC-beta
      gene transcription in CEM cells.

PMID- 2001453
TI  - Cytogenetic studies in untreated Hodgkin's disease.
AB  - Very little data have been published on cytogenetic abnormalities in Hodgkin's
      disease (HD) and their correlation with clinicopathologic features are scanty. We
      have performed chromosomal analysis of lymph nodes from 60 previously untreated
      HD patients and obtained analyzable metaphases in 49 patients (82%). Chromosomal
      abnormalities were found in 33 patients (55%) but only 31 karyotypes could be, at
      least partially, described. Twenty-nine cases showed numerical abnormalities that
      involved all chromosomes with the exception of chromosomes 13 and Y, which were
      gained less frequently and lost more frequently than other chromosomes.
      Structural abnormalities were found in 30 cases, involving all chromosomes except
      Y. Chromosomal regions 12p11-13, 13p11-13, 3q26-28, 6q15-16, and 7q31-35 were
      rearranged in more than 20% of the analyzable cases. No correlation was found
      between cytogenetic findings and initial characteristics. When compared with
      diffuse B-cell lymphomas, defects in regions 2p25 (P less than .01), 12p11-13 (P
      less than .01), 13p11-13 (P less than .01), 14p11 (P less than .01), 15p11-13 (P
      less than .02), and 20q12-13 (P less than .05) were more frequent in HD. When
      compared with T-cell lymphomas, only defects in regions 12p12-13 (P less than
      .01) and 13p11-13 (P less than .01) were more frequent in HD. Failure to obtain
      analyzable metaphases was correlated with stage IV of the disease (P less than
      .05) and with a poor survival (P less than .01), but cytogenetic results showed
      no other correlation with clinical outcome. We conclude that molecular studies in
      HD should be focused on the short arms of chromosomes 12 and 13. Determination of
      the clinical significance of cytogenetic findings will require a larger number of
      patients and a longer follow-up period.

PMID- 2001454
TI  - Protection from arabinofuranosylcytosine and n-mustard-induced myelotoxicity
      using hemoregulatory peptide pGlu-Glu-Asp-Cys-Lys monomer and dimer.
AB  - We have previously shown that the synthetic peptide pGlu-Glu-Asp-Cys-Lys (pEEDCK
      monomer) inhibits the cytostatic drug-induced proliferation of hematopoietic stem
      cells CFU-S. Keeping CFU-S quiescent by pEEDCK treatment renders them insensitive
      to cycle-specific cytostatic drugs and leads to reduced toxicity. Here we show
      that pEEDCK application during repeated (twice) administration of clinically
      relevant (nonlethal) 1-beta-D-arabinofuranosylcytosine (Ara-C) doses reduced the
      percentage of CFU-S in S-phase from 60%-70% to 25%-30% and led to a sustained
      stem cell number in the bone marrow (BM), whereas unprotected mice had lost about
      75% of their CFU-S population. Owing to its cysteine content, the pEEDCK monomer
      is easily oxidized. The resulting dimer (pEEDCK)2 is a potent stimulator of
      hematopoiesis. As we show, it can be used for postchemotherapy acceleration of
      hematologic recovery, similar to the use of recombinant hematopoietic growth
      factors. A single injection of 30 micrograms/kg pEEDCK monomer to mice 2 hours
      before the second Ara-C injection retarded onset of neutropenia (by 2 to 3 days)
      and improved recovery after depression. The quantitative degree of neutropenia
      was not changed. Postchemotherapy (Ara-C administered twice, followed by N
      mustard) infusion of the stimulatory (pEEDCK)2 dimer (1.4 micrograms/kg/d)
      produced a 4.6-fold increase of progenitor levels (6.7 CFU-GM/1,000 BM cells v
      1.45 CFU-GM/1,000 in normal mice) 2 days after the end of the cytostatic
      treatment when CFU-GM were not detectable in unprotected mice. This increase was
      followed after several days by strongly elevated granulocyte counts, which
      remained high for approximately 1 week. Up to 75% of the peripheral leukocytes
      were mature polymorphonuclear leukocytes (PMN) during this phase. Ara-C (twice)
      and monomer treatment as above followed by dimer infusion resulted in the
      complete protection of hematopoiesis. Mice treated with the protective pEEDCK
      monomer plus stimulatory dimer did not develop the leukocyte depression noted in
      unprotected animals. The inhibitory monomer appears to keep the stem cell
      population numerically and qualitatively intact, thus providing optimum target
      cell conditions for the subsequent stimulator (dimer) treatment. Our results show
      that the hemoregulatory peptide monomer and dimer can be used for improving the
      hematologic status of mice treated with clinically relevant doses of cytostatic
      drugs (antimetabolite and alkylating, alone and in combination). Combining both
      peptides can prevent occurrence of neutropenia completely. Both peptides can be
      obtained easily by chemical synthesis and are also active on human cells. They
      are thus highly promising candidates for application as multilevel hemoprotectors
      in cancer chemotherapy.

PMID- 2001455
TI  - Vanillin, a potential agent for the treatment of sickle cell anemia.
AB  - Vanillin, a food additive, has been evaluated as a potential agent to treat
      sickle cell anemia. Earlier studies indicated that vanillin had moderate
      antisickling activity when compared with other aldehydes. We have determined by
      high performance liquid chromatography that vanillin reacts covalently with
      sickle hemoglobin (HbS) both in solution and in intact red blood cells. Hemoscan
      oxygen equilibrium curves show a dose-dependent left shift, particularly at low
      oxygen tensions. Rheologic evaluation (pO2 scan Ektacytometry) of vanillin
      reacted HbS erythrocytes shows a dose-dependent inhibition of deoxygenation
      induced cell sickling. Ektacytometry also suggests that vanillin may have a
      direct inhibitory effect on HbS polymer formation. Vanillin has no adverse
      effects on cell ion or water content. X-ray crystallographic studies with
      deoxyhemoglobin (HbA)-vanillin demonstrate that vanillin binds near His 103
      alpha, Cys 104 alpha, and Gln 131 beta in the central water cavity. A secondary
      binding site is located between His 116 beta and His 117 beta. His 116 beta has
      been implicated as a polymer contact residue. Oxygen equilibrium, ektacytometry,
      and x-ray studies indicate that vanillin may be acting to decrease HbS
      polymerization by a dual mechanism of action; allosteric modulation to a high
      affinity HbS molecule and by stereospecific inhibition of T state HbS
      polymerization. Because vanillin is a food additive on the GRAS (generally
      regarded as safe) list, and because it has little or no adverse effects at high
      dosages in animals, vanillin is a candidate for further evaluation as an agent
      for the treatment of sickle cell disease.

PMID- 2001456
TI  - Molecular characterization of beta-thalassemia intermedia in patients of Italian
      descent and identification of three novel beta-thalassemia mutations.
AB  - In this study, we have defined by dot-blot analysis with allelic specific
      oligonucleotide probes or direct sequencing on amplified DNA the beta-thalassemia
      mutations in a large group of patients (23) of Italian descent with thalassemia
      intermedia. These patients had one parent with either the silent beta-thalassemia
      carrier phenotype or borderline-normal hemoglobin A2 (HbA2) levels (2.5% to
      3.5%). Nearly all were genetic compounds for a severe beta-thalassemia mutation
      and a beta-thalassemia mutation associated with high residual output of beta
      globin chains (beta + intervening sequence [IVS]-I-nt6, beta -87, beta -101),
      indicating that inheritance of a mild beta-thalassemia allele, even in a single
      dose, is the most common molecular mechanism producing thalassemia intermedia in
      the Italian population. In three cases, in whom we failed to define by dot-blot
      analysis the mutations, we sequenced the beta + globin gene and found three novel
      beta-thalassemia mutations, which are certainly very rare because they have been
      hitherto detected solely in a single patient. These mutations consist of: (1) a T
      A substitution at position 2 of IVS-I, in a patient compound heterozygote for
      this mutation and the -87 promoter mutation; (2) a G-C substitution at position
      844 of IVS-II, in a patient heterozygous for this mutation who showed normal
      sequences at the in trans beta-globin gene (The reason for the presence of
      clinical manifestations in a beta-thalassemia heterozygote has not been
      defined.); and (3) a deletion of one nucleotide (-T) at codon 126, resulting in a
      frameshift and readthrough of the 5' untranslated region and most likely
      producing an elongated Hb molecule of 156 amino acid residues, in a patient
      heterozygous for this mutation with normal beta-globin gene sequences at the
      other locus.

PMID- 2001457
TI  - Molecular defect of a phosphoglycerate kinase variant (PGK-Matsue) associated
      with hemolytic anemia: Leu----Pro substitution caused by T/A----C/G transition in
      exon 3.
AB  - We have identified the mutation in a phosphoglycerate kinase variant (PGK-Matsue)
      associated with severe enzyme deficiency, congenital nonspherocytic hemolytic
      anemia, and mental disorders. The mRNA coding for PGK was reverse transcribed and
      amplified by the polymerase chain reaction. Nucleotide sequencing of the variant
      cDNA showed a point mutation, a T/A----C/G transition in exon 3 of the variant
      gene. No other mutation was found in all coding regions of PGK-Matsue. The
      nucleotide change created an additional NciI cleavage site in the variant gene;
      thus, the NciI fragment types detected by Southern blot hybridization differ in
      the variant DNA and normal DNA. The mutation should cause Leu----Pro substitution
      at the 88th position from the NH2-terminal Ser of PGK. Because the Leu----Pro
      substitution is expected to induce serious perturbation and instability in the
      protein structure, the severe enzyme deficiency is mainly caused by more rapid in
      vivo denaturation and degradation of the variant enzyme.

PMID- 2001458
TI  - Rate of deoxygenation and rheologic behavior of blood in sickle cell anemia.
AB  - To understand the relationship between deoxygenation rate, rheologic behavior,
      and red blood cell (RBC) morphologic characteristics of blood in sickle (SS) cell
      anemia, washed oxy SS RBC suspensions (hematocrit, 40%) were subjected to
      relatively fast and gradual deoxygenation procedures. Relatively fast
      deoxygenation resulted in 50% decline in percent hemoglobin oxygen saturation
      (%HbO2) within 1 minute. The SS suspensions following relatively fast
      deoxygenation showed two distinct phases in viscosity profiles. First, there was
      a sharp increase in individual viscosities to a peak value at 7 minutes of
      deoxygenation. Second, prolonged deoxygenation resulted in a 27% to 37% decrease
      in individual viscosities at 30 minutes as compared with the respective peak
      values at 7 minutes. Most of the viscosity increase (ie, about fourfold) occurred
      within the first 3 minutes of relatively fast deoxygenation. Scanning electron
      microscopy and differential morphologic analysis of deoxy cells showed that at 7
      minutes a majority of cells had a granular appearance that was characterized by a
      bumpy irregular surface and the presence of small spicule-like projections.
      Prolonged deoxygenation resulted in the appearance of a large percentage of
      elongated cells that were unlike typical sickle cells. Transmission electron
      microscopy showed that the elongated shape resulted from the alignment of HbS
      polymers into long projections. In contrast, gradual deoxygenation over a period
      of 30 minutes resulted in a progressive increase in viscosity and in the
      formation of typical sickle shapes and holly leaf cells. The results show that at
      matching %HbO2, the SS suspensions containing mainly granular shaped cells after
      7 minutes of relatively fast deoxygenation are as viscous as the gradually
      deoxygenated suspensions that contain classic sickle shapes and holly leaf forms,
      while the suspensions having a large percentage of elongated cells (30 minutes
      after relatively fast deoxygenation) are the least viscous. The two distinct time
      dependent viscosity phases observed after relatively fast deoxygenation probably
      result from differences in the RBC shape characteristics reflecting physical
      attributes of the polymer, which could affect cell orientation in the viscometric
      flow.

PMID- 2001459
TI  - Calcium ionophore, A23187, induces commitment to differentiation but inhibits the
      subsequent expression of erythroid genes in murine erythroleukemia cells.
AB  - Murine erythroleukemia (MEL) cells are a useful model for studying the processes
      that regulate erythroid differentiation because exposure of these cells to a
      variety of chemical inducing agents results in expression of erythroid-specific
      genes and the resultant loss of cellular immortality. Previously it has been
      suggested that the calcium ionophore, A23187, has effects on the early cellular
      events that lead to the commitment of these cells to differentiation, but was not
      in itself sufficient to induce differentiation. We demonstrate here that A23187,
      as well as another calcium ionophore, ionomycin, are capable of inducing
      commitment to differentiation. Unlike other inducing agents, continual exposure
      to A23187 inhibits transcription of the erythroid-specific genes, beta-globin and
      Band 3. This effect is not attributable to an increase in cytosolic calcium
      concentration, because cells induced by ionomycin produce normal amounts of
      hemoglobin. These effects of A23187 on MEL cells confirm that commitment to
      differentiation is a distinct event from the subsequent transcriptional
      activation of erythroid genes. The ability of both ionophores to induce
      commitment to differentiation suggests that an increase in cytosolic calcium can
      trigger commitment to differentiation. These agents should prove useful in
      investigating the cellular processes that are responsible for commitment to
      differentiation.

PMID- 2001460
TI  - The Senegal DNA haplotype is associated with the amelioration of anemia in
      African-American sickle cell anemia patients.
AB  - We have previously determined that in African sickle cell anemia (SS) patients
      three different beta-like globin gene cluster haplotypes are associated with
      different percent G gamma (one of the two types of non-alpha chains comprising
      hemoglobin F [HbF]), mean percent HbF, and percent dense cells. We report now
      that in adult New York SS patients, the presence of at least one chromosome with
      the Senegal haplotype is associated with higher Hb levels (1.2 g/dL higher) than
      is found for any other non-Senegal haplotype (P less than .004). The percent
      reticulocytes and the serum bilirubin levels were lower in these patients. When
      the effect of alpha-gene number was analyzed by examining a sample of SS patients
      with concomitant alpha-thalassemia, the same results were obtained. Because the
      HbF level is significantly higher among the Senegal haplotype carriers in this
      sample, the inhibitory effect on sickling of this Hb variant may be one of the
      reasons for the haplotype effect. We conclude that the Senegal beta-like globin
      gene cluster haplotype is associated with an amelioration of the hemolytic anemia
      that characterizes sickle cell disease.

PMID- 2001462
TI  - Trisomy 6: a recurring cytogenetic abnormality associated with marrow hypoplasia.

PMID- 2001461
TI  - Differential tissue expression of the Lewis blood group antigens: enzymatic,
      immunohistologic, and immunochemical evidence for Lewis a and b antigen
      expression in Le(a-b-) individuals.
AB  - The Lewis blood group system comprises two main carbohydrate antigens, Le(a) and
      Le(b). Lewis typing has traditionally been based on serologic determinations
      using erythrocytes and saliva. Several recent studies have demonstrated that
      erythrocyte Lewis phenotype may change during pregnancy or disease, and
      inappropriate Lewis antigens have been found in both normal and neoplastic
      tissue. To evaluate whether these observations are in conflict with the presently
      proposed genetic and biosynthetic basis of the Lewis blood group system, we
      performed a combined enzymatic, immunohistologic, and immunochemical study of
      Lewis antigen expression in normal and neoplastic tissues, as well as
      erythrocytes, plasma, and saliva of Le(a-b-)-typed individuals. Of six cancer
      bearing patients typed Le(a-b-), three were identified as nongenuine owing to the
      presence of alpha 1----4fucosyltransferase activity (alpha 1----4FT) and Lewis
      antigens in saliva and three were identified as genuine (lacking alpha 1----4FT
      and Lewis antigens in saliva). These genuine Le(a-b-) individuals were shown to
      express significant alpha 1----4FT in tissues, and Lewis antigens were detected
      in tissues by immunohistology as well as immunochemistry. We conclude that the
      Lewis phenotype obtained by serologic determination of erythrocytes and saliva
      does not apply to all tissues. We discuss biosynthetic and genetic consequences
      of this finding.

PMID- 2001463
TI  - Wegener's autoantigen and leukemia.

PMID- 2001464
TI  - Heterogeneity of presynaptic serotonin receptors on sympathetic neurones in blood
      vessels.
AB  - Presynaptic serotonin (5-HT) receptors on the postganglionic sympathetic nerves,
      which mediate inhibition of noradrenaline release in blood vessels of various
      species and which interact with the presynaptic alpha 2-autoreceptors, are
      heterogeneous. In the rat vena cava, they are of the 5-HT1B subtype, in the pig
      coronary artery they belong to a novel, so far unknown class of 5-HT receptors,
      and in the human saphenous vein they could be classified as 5-HT1D. These results
      point to marked species differences and the need to carry out experiments in
      human vascular preparations. Presynaptic 5-HT receptors may be involved in the
      mechanism of action of the new antimigraine drug sumatriptan.

PMID- 2001465
TI  - Role of potassium channels in the vascular response to endogenous and
      pharmacological vasodilators.
AB  - Many endogenous and pharmacological vasodilators hyperpolarize vascular smooth
      muscle and this response appears to be due to an increased conductance to
      potassium ions. The hyperpolarization may contribute to the mechanism of dilation
      by causing voltage-dependent calcium channels to close. Recent evidence indicates
      that the response to hyperpolarizing vasodilators is mediated through activation
      of ATP-sensitive potassium (KATP) channels. Single KATP channels on isolated
      vascular smooth muscle cells are activated by cromakalim and calcitonin gene
      related peptide (CGRP). This response is inhibited by glibenclamide. Cromakalim,
      CGRP and other vasodilators hyperpolarize and relax arteries in vitro and these
      responses are reversed by glibenclamide. The hypotensive effects of these agents
      in vivo are antagonized by glibenclamide. We propose that activation of KATP
      channels and the associated membrane hyperpolarization represents an important
      general mechanism of vasodilation.

PMID- 2001466
TI  - Pressure and flow: are these the true vascular neuroeffectors?
AB  - Activity of the efferent nerve supply to the vasculature results in local
      increases or decreases in the tone of the vascular smooth muscle cells with
      corresponding changes in diameter. This results in changes in pressure and flow,
      both of which, because they too influence the vascular wall, extend the influence
      potentially to the entire bed. As the vascular bed is sensitive to pressure - an
      increase causing vasoconstriction - and to flow - an increase causing variable
      amounts of contraction and relaxation - the final results must reflect their
      interaction. Thus, the direct changes in artery tone brought about by neural
      activity are modified and diffused throughout the entire regional arterial system
      by the concomitant changes in the flow and pressure of the blood.

PMID- 2001467
TI  - Hypernoradrenergic innervation and vascular smooth muscle hyperplastic change.
AB  - Two distinguishing features of the vasculature of the spontaneously hypertensive
      rat (SHR) are an increased sympathetic innervation and vascular smooth muscle
      hyperplasia. Evidence supporting the existence of hypernoradrenergic innervation
      and vascular smooth muscle cell hyperplasia is presented with emphasis upon the
      possible interrelationships between the two events. The results of experiments
      designed to explore this relationship are presented and include the determination
      of the role of endogenous nerve growth factor (NGF) and the influence of
      exogenous NGF on the development of sympathetic innervation of blood vessels and
      blood pressure change. Attention is focused upon elevated levels of 3
      methylhistidine (a biochemical marker for contractile proteins) in the mesenteric
      vasculature of the SHR. The potential relationships between hypernoradrenergic
      innervation and increased concentrations of 3-methylhistidine are explored.

PMID- 2001469
TI  - Development of collaterals in the cerebral circulation.
AB  - Sudden occlusion of the middle cerebral artery (MCA) in normotensive rats
      increases blood flow through anastomosing branches into the territory of the
      occluded artery. Three weeks after MCA occlusion, anastomoses to anterior
      cerebral branches are increased by more than 50% in luminal diameter. One month
      after MCA occlusion, blood flow and blood flow reserve to the territory of the
      occluded MCA are returned to normal levels. In stroke-prone spontaneously
      hypertensive rats (SHRSP), the anastomoses are significantly narrower and blood
      flow through the anastomoses is less than in normotensive rats. Tissue infarction
      invariably develops in the territory of the occluded MCA in SHRSP. We propose
      that the luminal width of the anastomosis is a major determinant of blood flow
      into the territory of the occluded artery and of the amount of tissue protected
      from infarction by collateral circulation.

PMID- 2001468
TI  - Two indices of functional damage of the artery wall parallel the time course of
      irreversible narrowing in experimental vasospasm in the rabbit.
AB  - Autologous blood placed around the basilar artery caused angiographic narrowing
      with a biphasic time course. The first immediate phase was reversed by
      intraarterial papaverine; the second exhibited an increasing component of
      narrowing which was papaverine-resistant. In vitro studies showed that vessels
      became increasingly stiffer, less capable to develop active tone, and less
      responsive to vasoconstrictors and vasodilators. The papaverine-resistant
      component of angiographic narrowing (in vivo) could be directly correlated with
      loss of contractility and increased artery wall stiffness (in vitro).

PMID- 2001470
TI  - Heterogeneity of capillary perfusion.
AB  - Heterogeneity represents a general feature of capillary networks. All of the
      parameters which describe hemodynamic, geometric or functional aspects of such
      networks exhibit considerable spatial dispersion. This is to some extent the
      result of the morphological and topological design of the network, reinforced by
      the nonhomogeneous nature of the flowing blood. Temporal dispersions are
      introduced by smooth muscle activity, which may be rhythmic or just oscillatory,
      but also by the passage of white cells causing transient perturbations. The
      functional relevance of perfusion heterogeneity follows from its effect on
      exchange efficiency. While evidence for the existence of physiological control
      mechanisms of heterogeneity is uncertain, intranetwork communication between
      upstream and downstream vessel segments appears to support the adaptation of
      supply to demand under physiological conditions.

PMID- 2001471
TI  - Vascular production and regulation of angiotensin.
AB  - To test the hypothesis that angiotensin (Ang) I and II are produced by blood
      vessels, we investigated the formation of both Ang I and Ang II in isolated,
      perfused rat hindquarters. To characterize the nature of this production further,
      we modulated plasma renin by total or subtotal nephrectomy and tested the effects
      of exogenous renin and renin substrate on vascular Ang formation. Assays of the
      perfusate by high-performance liquid chromatography and radioimmunoassay
      demonstrated the spontaneous release of Ang I and Ang II from the hindlimb
      vasculature. Conversion of Ang I to Ang II in hindquarter vasculature was
      approximately 75% and was totally suppressed by captopril. The spontaneous
      formation of Ang peptides was abolished by bilateral nephrectomy but was not
      affected by subtotal 5/6 nephrectomy. The addition of purified rat
      angiotensinogen to the preparation increased Ang II levels. The infusion of renin
      into the hindlimb vasculature led to substantial increases in local Ang formation
      and also raised the perfusion pressure. Both effects were sensitive to captopril
      and to the renin inhibitor H-142. The data indicate that Ang I and Ang II are
      produced locally within blood vessels. However, the origin of vascular renin
      remains controversial. Our results suggest that part of the enzyme is taken up
      from plasma.

PMID- 2001472
TI  - Role of vascular wall renin: intracellular and extracellular mechanism.
AB  - Inhibitors of angiotensin-converting enzyme, renin and angiotensin II receptor
      lower the blood pressure of spontaneously hypertensive rats (SHRs) used as a
      model of essential hypertension. Since their plasma renin levels were normal or
      subnormal, renin in the vascular tissue was considered to play a key role in the
      maintenance of the hypertension. To clarify the source and localization of
      vascular renin in SHRs, the effects on blood pressure of antirenin antibodies,
      the converting enzyme inhibitors delapril and enalapril, and the angiotensin II
      receptor antagonist DuP 753 were examined in intact and bilaterally
      nephrectomized SHRs and their normotensive controls. The efficient hypotensive
      action of the renin antibody indicated that renin of the renal origin is a
      dominant factor. The gradual but complete disappearance of the antihypertensive
      action of these inhibitors of the renin-angiotensin system upon bilateral
      nephrectomy indicated the importance of membrane-associated renin of the renal
      origin and angiotensin-converting enzyme in the maintenance of the spontaneous
      hypertension.

PMID- 2001473
TI  - Is there a role for the vascular renin-angiotensin system in the determination of
      vascular structure?
AB  - This paper reviews previous work done by my laboratory to investigate the effect
      of treatment with angiotensin-converting enzyme (ACE) inhibitors on blood
      pressure and small artery structure in spontaneously hypertensive rats (SHRs).
      First, the data confirm that ACE inhibitors have a persistent effect on blood
      pressure in SHRs when treatment is withdrawn. The effect of the ACE inhibitors
      was dose-dependent, but the persistent effect was not dose-dependent. This
      suggests that the persistent effect of ACE inhibitors on blood pressure in SHRs
      is not mediated through vascular structure. Secondly, the data demonstrate that,
      although ACE inhibitors have dose-dependent effects on both blood pressure and
      vascular structure, in experiments where different drugs were used, the effect of
      ACE inhibitors on vascular structure seems to be explained primarily through
      their effect on blood pressure, rather than any specific drugs effect.

PMID- 2001474
TI  - Role of the local renin-angiotensin system in the autoregulation of the cerebral
      circulation.
AB  - Inhibition of angiotensin-converting enzyme (ACE) shifts the limits of cerebral
      blood flow autoregulation toward lower blood pressure values. This effect seems
      to be mediated by blocking the formation of angiotensin II on the luminal side of
      the larger cerebral resistance vessels. Baseline cerebral blood flow (the flow
      within the autoregulatory limits) is not changed by acute or chronic ACE
      inhibition. An interaction between the vascular reninangiotensin and the
      sympathetic nervous system is present. Activation of the latter inhibits the
      downwards shift of the upper limit of autoregulation following ACE inhibition.

PMID- 2001475
TI  - Methodological approaches used for the study of the coronary microcirculation in
      situ.
AB  - Measurements of coronary microvascular parameters in situ are difficult because
      of the thickness of the heart muscle and cardiac contraction. Both of these
      problems hamper the visualization of the coronary microcirculation. We have
      refined methodological approaches that enable the study of the coronary
      microcirculation in situ. In the first approach, microvessels can be visualized
      in the beating heart using a preparation that compensates for cardiac motion by
      creating an illusion that the heart is motionless. This is accomplished by
      flashing a stroboscopic light source once per heart cycle at the same point in
      each cycle and synchronizing a ventilator with the cardiac cycle. Images of
      microvessels can be obtained using standard intravital video-microscopic
      techniques. To visualize the intramural and subendocardial microcirculation,
      studies are completed in isolated hearts. In this preparation, measurements of
      microvascular diameters and pressures can be performed in both the subepicardial
      and subendocardial microcirculations. This latter approach allows insight into
      transmural differences of coronary microvascular regulation.

PMID- 2001476
TI  - Spatial and temporal resolution of serotonin-induced changes in intracellular
      calcium in a cultured arterial smooth muscle cell line.
AB  - Ca2+ transients (1-2 microM) evoked by serotonin (5-HT) in cultured A7r5 cells
      were studied using fura-2 and digital imaging microscopy. Fura-2 was introduced
      into cells either by incubation with its acetoxymethyl ester analogue fura-2/AM
      or by transient ATP-induced permeabilization of the sarcolemma such that the free
      fura-2 entered the cell directly. The distribution of cytoplasmic Ca2+ in
      unstimulated cells loaded by the former method was heterogeneous, reflecting, in
      part, separate pools of Ca2+ in the cytosol and sarcoplasmic reticulum (SR). In
      contrast, the distribution of Ca2+ was uniform in cells loaded with fura-2 by
      transient permeabilization; this reflected the restriction of fura-2 to the
      cytosol. Average Ca2+ in these cells was substantially lower than that in fura
      2/AM-loaded cells, because SR Ca2+ influences the fura-2 signal from fura-2/AM
      loaded cells, but not from cells loaded with free fura-2. The differences in the
      Ca2+ distribution measured by the two loading methods were also evident during
      the course of 5-HT-evoked Ca2+ transients. Spatial and temporal resolution of the
      rising phase of 5-HT-evoked Ca2+ transients in fura-2/AM-loaded cells revealed
      that the onset of the Ca2+ transients was first manifested as small regions of
      elevated Ca2+ that subsequently expanded until peak apparent intracellular Ca2+
      levels were present in virtually all of the nonnuclear regions of the cells. The
      rate of rise of Ca2+ varied in different cell regions with the nucleus responding
      the slowest.

PMID- 2001477
TI  - Release of vasoactive peptides from autonomic and sensory nerves.
AB  - Release of specific vasoactive peptides occurs upon activation of perivascular
      parasympathetic (vasoactive intestinal polypeptide and peptide histidine
      isoleucine), sympathetic (neuropeptide Y) and sensory (calcitonin gene-related
      peptide and tachykinins) nerves. These peptides may serve as cotransmitters with
      acetylcholine and noradrenaline with interactions both at the pre- and
      postjunctional levels. Some long-lasting nonadrenergic, noncholinergic vascular
      effects upon nerve activation may thus be peptide-mediated. Strong activation
      seems to be necessary for peptidergic transmission in the parasympathetic and
      sympathetic system while local sensory mechanisms may occur even at single
      impulses.

PMID- 2001478
TI  - Innervation and effects of dilatory neuropeptides on cerebral vessels. New
      aspects.
AB  - The cerebral circulation is supplied with two vasodilator systems: the
      parasympathetic system storing vasoactive intestinal peptide, peptide histidine
      isoleucine, acetylcholine and in a subpopulation of nerves neuropeptide Y, and
      the sensory system, mainly originating in the trigeminal ganglion, storing
      substance P, neurokinin A and calcitonin gene-related peptide (CGRP). Recent
      knowledge of the innervation and effects of the dilator neuropeptides in the
      cerebral circulation is reviewed. Their role in the pathophysiology of
      subarachnoid hemorrhage and migraine has now received attention, with
      documentation of a clear linkage with the release of CGRP. In subarachnoid
      hemorrhage, other perivascular peptides are, to a lesser extent, involved.

PMID- 2001479
TI  - Postischemic cerebral blood flow and neuroeffector mechanisms.
AB  - The influence of neuroeffector mechanisms in the regulation of postischemic
      cerebral blood flow was investigated by microsphere determination in 8 cats after
      chronic unilateral vascular deafferentation by trigeminal ganglionectomy. The
      animals were subjected to 90 min of reperfusion following 10 min of global
      ischemia induced by 4-vessel occlusion and systemic hypotension. Cortical
      hyperemia 30 min after reperfusion was attenuated by up to 48% in cortical gray
      matter ipsilateral to the side of trigeminal ganglionectomy (p less than 0.01).
      Axon reflex mechanisms involving the release of neuropeptides from peripheral
      sensory nerve fibers, such as substance P (SP), calcitonin gene-related peptide
      (CGRP) and neurokinin A (NKA), mediate this response. SP and NKA cause
      vasodilation by endothelium-dependent mechanisms (endothelium-dependent relaxing
      factor), whereas CGRP relaxes vascular smooth muscle by direct receptor
      interactions. Studies were therefore undertaken to determine the extent to which
      endothelium-dependent mechanisms mediate the hyperemia following global cerebral
      ischemia. In 7 intact cats, the postischemic response of pial arterioles to the
      topical application of acetylcholine (ACh; 10(-7) M), an endothelial-dependent
      vasodilator, was measured using a closed cranial window technique. Although ACh
      increased pial arteriolar caliber by 17% under resting conditions, the same dose
      elicited a vasoconstrictor response (87% of pre-ACh diameter 30 min after
      reperfusion) for the first 60 min of reperfusion after 10 min of ischemia. ACh
      induced vasodilation was restored by 75 min (105%), but was less than control
      even at 120 min (109 vs. 117%; p less than 0.05).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 2001480
TI  - Exposure to vapors of benzene and other aromatic solvents in tank truck loading
      and delivery.

PMID- 2001481
TI  - Effects of nitrogen compounds with hexobarbital induced sleep in Swiss albino
      mice.

PMID- 2001483
TI  - Transfer of methylmercury to hens' eggs after oral administration.

PMID- 2001482
TI  - Effects of surfactants on the contents of metallothionein, heme and hemoproteins
      and on the activities of heme oxygenase and drug-metabolizing enzymes in rats
      pretreated with phenobarbital or beta-naphthoflavone.

PMID- 2001484
TI  - Short and medium effects on the environment of Valencia, Spain, of the Chernobyl
      nuclear plant accident.

PMID- 2001485
TI  - Comparison of the effect of metallic copper and copper nitrate (Cu(NO3)2.3H2O) on
      Ceriodaphnia dubia utilizing the three-brood test.

PMID- 2001486
TI  - Bioconcentration of endosulfan in different body tissues of estuarine organisms
      under sublethal exposure.

PMID- 2001487
TI  - Effects of phthalate esters on the locomotor activity of the freshwater amphipod
      Gammarus pulex.

PMID- 2001488
TI  - Changes in poultry litter toxicity with simulated acid rain.

PMID- 2001489
TI  - Assessing atrazine persistence in soil following a severe drought.

PMID- 2001490
TI  - Enzyme immunoassay for the determination of atrazine residues in soil.

PMID- 2001491
TI  - Adsorption and desorption of linuron by activated charcoals.

PMID- 2001492
TI  - Effect of exposure time on the sorption of pesticide emulsifiable concentrates
      through microporous fabrics.

PMID- 2001493
TI  - Use of human metabolic studies and urinary arsenic speciation in assessing
      arsenic exposure.

PMID- 2001494
TI  - Dermatitis from a woman's contaminated slip.

PMID- 2001495
TI  - Contamination of soils and sediments in the vicinity of a mercury recovery plant.

PMID- 2001496
TI  - Concentrations of trace and other elements in the organs of wild rats and birds
      from the northern Guinea savanna of Nigeria.

PMID- 2001497
TI  - Effects of broadcasting and of drilling methiocarb molluscicide pellets on field
      populations of wood mice, Apodemus sylvaticus.

PMID- 2001498
TI  - Calcium metabolism and bone mineralization in female rats fed diets marginally
      sufficient in calcium: effects of increased dietary calcium intake.
AB  - Experiments were carried out to determine the ability of female rats with poorly
      mineralized skeletons to increase bone mineralization in response to increased
      dietary Ca consumption. We specifically addressed this question with regard to
      two different periods of the life cycle: the period of sexual maturation (6-9
      weeks of age), and in animals that had attained adult rates of skeletal
      mineralization (100 days of age). We found that at both stages, increased dietary
      Ca consumption resulted in increased trabecular bone volume and total bone Ca. In
      the younger animals, it was found that dietary history influenced the disposition
      of bone mineral. Animals that were initially Ca-deprived exhibited increased
      trabecular bone and decreased cortical thickness compared to animals continuously
      fed 0.5% Ca. Ovariectomy of mature animals reduced but did not eliminate the
      response to increased Ca intake.

PMID- 2001499
TI  - A stable analogue of thromboxane A2, 9,11-epithio-11,12-methanothromboxane A2,
      stimulates bone resorption in vitro and osteoclast-like cell formation in mouse
      marrow culture.
AB  - Thromboxane A2 (TXA2) is a powerful promoter of platelet aggregation and smooth
      muscle contraction. However, this compound is highly unstable and is rapidly
      hydrated to a more stable metabolite, thromboxane B2 (TXB2). TXA2 has been
      considered to be involved in bone resorption, in particular bone loss caused by
      inflammatory diseases and by orthodontic treatment. However precise mechanisms of
      bone resorption caused by TXA2 have not yet been proved because of its highly
      unstable nature. Recently, a chemically stable analogue of TXA2, 9,11-epithio
      11,12-methanothromboxane A2 (STA2), was successfully synthesized. Using this
      synthetic compound, we examined its in vitro bone resorbing activity and
      induction of osteoclast-like cells in a mouse marrow culture system in comparison
      with related compounds with bone resorbing activity. Like prostaglandin E2
      (PGE2), a well-known bone resorbing agent, STA2 time- and dose-dependently
      stimulated the release of 45Ca from prelabelled mouse calvariae. Both STA2 and
      PGE2 induced the accumulation of cAMP in mouse calvariae. The TXA2 antagonist,
      ONO-3708, inhibited STA2-induced release of 45Ca. TXB2 induced neither bone
      resorption nor cAMP accumulation. When mouse marrow cells were cultured with STA2
      for 8 days, osteoclast-like multinucleated cells appeared in parallel with the
      increase of the amount of STA2 added. Again TXB2 showed no effect on osteoclast
      like cell formation. These results indicate a role for TXA2 in some form of bone
      resorption.

PMID- 2001500
TI  - Transdifferentiation of hypertrophic chondrocytes into osteoblasts in murine
      fetal metatarsal bones, induced by co-cultured cerebrum.
AB  - The fate of hypertrophic chondrocytes in 17-day-old metatarsal bones of fetal
      mice was studied in a culture system in which these cells were kept confined to
      their lacunae. Because the periosteum had been stripped off, osteoclasts could
      not invade the long bone and resorb the lacunar walls. The majority of the
      hypertrophic chondrocytes stayed alive and dedifferentiated gradually into cells
      with the appearance of stromal cells. When the long bones were co-cultured with
      pieces of cerebrum, the chondrocytes transdifferentiated into osteoblasts. We
      followed this process from day to day. The cells produced bone matrix that
      immunostained for collagen type I and osteocalcin. To exclude with certainty the
      possibility that the intralacunar osteoblasts had derived from remaining
      periosteal osteoprogenitor cells that invaded the lacunae, the long bones were
      pre-cultured with cytochalasin D, which inhibits cell proliferation and
      migration. After removal of the drug this effect persisted until after
      transdifferentiation had occurred. This proved that the bone matrix producing
      osteoblasts inside the cartilage lacunae were transdifferentiated chondrocytes.
      The transdifferentiation stimulating factor from brain tissue is still unknown.

PMID- 2001501
TI  - Bone growth and mineralisation in children aged 4 to 10 years.
AB  - The relationships between bone width and mineral content and age, sex, height and
      weight were studied in 420 children aged 4-10 years living in Cambridge using
      single photon absorptiometry. The relationship of bone width with bone mineral
      content was significantly different between the sexes after adjusting for
      differences in body size. In addition, bone width in boys was found to be greater
      for a given height and weight; changes in weight had a greater effect on bone
      width in boys than in girls. Prediction equations for bone width and mineral
      content based on height and weight are given, which should enhance the
      application of single photon absorptiometry in clinical practice.

PMID- 2001502
TI  - Cardiac cachexia.

PMID- 2001503
TI  - Good surveys guide.

PMID- 2001504
TI  - Referrals to rheumatology.

PMID- 2001505
TI  - The psychological aftermath of war.

PMID- 2001506
TI  - Teaching junior doctors practical procedures.

PMID- 2001507
TI  - Practical ways of alleviating auditory hallucinations.

PMID- 2001508
TI  - Quality of prescribing of intravenous antibiotics in a district general hospital.

PMID- 2001510
TI  - Confidence intervals and sample sizes: don't throw out all your old sample size
      tables.

PMID- 2001509
TI  - Violence in general practice: a survey of general practitioners' views.
AB  - OBJECTIVE: To survey the extent of abuse and violence directed towards general
      practitioners during the course of their professional duties and to categorize
      the characteristics of such aggression. DESIGN: Retrospective survey of the views
      of a large sample of general practitioners by using a piloted postal
      questionnaire. SETTING: All medical practices in the west midlands. SUBJECTS: A
      total of 1093 general practitioners (40.6% of the total sample) who responded to
      the questionnaire. MAIN OUTCOME MEASURE: Number of incidents of aggression
      experienced by the general practitioners during a period of 12 months and the
      incidence of various precipitating factors. RESULTS: Although the response was
      low at 40.6%, this study is the largest published database on aggression towards
      family doctors. In all, 687 (62.9%) of the responders had experienced abuse or
      violence during the previous 12 months, and 191 (17.5%) had experienced some sort
      of abuse at least once a month and 11 (1%) had experienced verbal abuse every
      day. Even assuming that all of the non-responders did not experience any
      violence, then aggression in patients affects 25.5% of general practitioners in
      the west midlands. For those practitioners who had experienced aggression in
      patients the annual incidence of an event per general practitioner was 2.42. In
      all, 96 (14%) of these general practitioners thought that aggression was
      increasing. A total of 1520 (91.3%) of all incidents comprised verbal abuse or
      threats with no direct physical act. The surgery was the commonest location for
      aggression, with 942 (56.6%) incidents; however, 90 (62.5%) of the incidents
      involving assault or injury occurred during domiciliary visits and 22 (66%) of
      the injuries were received during night calls. Relatives were the aggressors in
      668 (37.6%) cases, anxiety was a precipitant in 435 (25.7%) cases, and a long
      wait in 183 (10.8%). CONCLUSIONS: Violence towards general practitioners is
      common and may be increasing. Some of the precipitants of aggression are
      potentially avoidable and practices should make strenuous attempts to identify
      such factors and remedy them. Staff training in interpersonal skills and
      recognising anxious or intoxicated patients is essential and should be
      supplemented by consideration of surgery layout and repair. Doctors should avoid
      delays for patients by rearranging booking policies or surgery times and lengths.
      Victims of aggression must be followed up. A prospective study or centralised
      recording of incidents should be funded.

PMID- 2001511
TI  - AIDS: it came for the carnival.

PMID- 2001512
TI  - Uniform requirements for manuscripts submitted to biomedical journals.
      International Committee of Medical Journal Editors.

PMID- 2001513
TI  - Maternity benefits.

PMID- 2001514
TI  - Tomography in deep vein thrombosis.

PMID- 2001515
TI  - Health care for people with mental handicap.

PMID- 2001516
TI  - Self management of asthma.

PMID- 2001517
TI  - Fast neutron treatment for squamous cell carcinoma.

PMID- 2001518
TI  - Recurrent hereditary polyserositis.

PMID- 2001519
TI  - Milk for babies and children.

PMID- 2001520
TI  - Children with head injuries.

PMID- 2001521
TI  - Hypothermia.

PMID- 2001522
TI  - HIV infection and foreign travel.

PMID- 2001523
TI  - Chemical weapons.

PMID- 2001524
TI  - Magnetic resonance imaging of the brain.
AB  - Magnetic resonance imaging (MRI) of the brain has become essential to a
      neurologic work-up. In Canadian centres where access to MRI is limited, use of
      this technique is usually restricted to assessment of disorders for which it is
      likely to provide unique information after computed tomography (CT); examples
      include abnormalities of the temporal lobes and posterior fossa, some diseases
      that show subtle or no abnormalities on CT (many inflammatory and demyelinating
      disorders) and cases in which detailed anatomic assessment is necessary (vascular
      malformation, congenital anomalies and many tumours). Although MRI of the brain
      has become quite standardized, recent developments such as improved gradient-echo
      imaging, new coil designs, magnetic resonance angiography and the use of contrast
      agents in MRI have resulted in improved speed and utility.

PMID- 2001525
TI  - Magnetic resonance techniques for blood-flow measurement and vascular imaging.
AB  - The authors review the history and physical principles behind vascular magnetic
      resonance imaging (MRI) techniques, developed to measure blood flow noninvasively
      and to display images of the vasculature. All these techniques have been used to
      create magnetic resonance angiograms, in which the vasculature is shown in a
      projection format similar to x-ray angiography. Signal loss limits the
      effectiveness of "white-blood" magnetic resonance angiography techniques, since
      slow flow and complex flow often cause a drop in signal and consequently a loss
      of accuracy in depicting vessel anatomy. "Black-blood" magnetic resonance
      angiography is described as a method that avoids these problems of signal loss.
      Selective black-blood magnetic resonance angiography is introduced as a technique
      for improving the visualization of the vasculature when other signal-void
      structures are present in the volume of interest.

PMID- 2001526
TI  - Ultrafast magnetic resonance imaging: diffusion and perfusion.
AB  - Echo-planar magnetic resonance imaging (MRI) can be used to measure apparent
      diffusion coefficients noninvasively in vivo, with scan times of 150 milliseconds
      or less, and to assess early ischemic effects in the feline experimental model,
      which has an occluded middle cerebral artery (MCA). The apparent diffusion
      coefficient in ischemic regions, which are identified later from vital staining,
      is significantly decreased from normal values within 1 hour after the MCA becomes
      occluded. A series of 10 echo-planar images that are progressively diffusion
      weighted can be collected in 1 minute (effective TR of 6 seconds).
      Semilogarithmic plots of image intensity versus gradient strength factors (b
      values) were linear. Collecting sequential gradient echo-planar images during the
      passage of a bolus of contrast medium is also useful when assessing perfusion or
      vascular integrity before and during ischemic episodes. After intravenous
      injection of dysprosium-diethylene triamine penta-acetic acid-bis(methylamide),
      typical signal losses of 40% to 80% were observed and were dose-dependent. Areas
      of possible ischemia identified from diffusion-weighted images did not lose
      signal intensity with the use of contrast medium and were seen as regions of
      relative hyperintensity, clearly discernible from normally perfused tissues.

PMID- 2001527
TI  - Recent advances in magnetic resonance imaging of musculoskeletal tumours.
AB  - Magnetic resonance imaging (MRI) has become the method of choice, where
      available, for the evaluation of musculoskeletal neoplasms. Recently, there has
      been interest and development in a number of areas in this field: (a) gradient
      echo (fast-scan) sequences, which may often be substituted for more time
      consuming T2-weighted sequences, are useful as localizing sequences and play an
      important role in intravenous contrast-enhanced scanning; (b) magnetic resonance
      contrast agents (e.g., gadolinium) improve delineation of tumours on static
      imaging and may help in estimating tumour aggressiveness with dynamic imaging;
      (c) STIR (short inversion time inversion recovery) increases lesion conspicuity;
      (d) spectroscopy, still an investigational area, may help in evaluating tumour
      response to chemotherapy and radiotherapy.

PMID- 2001528
TI  - Breast lymphoma: radiologic imaging and clinical appearances.
AB  - Lymphoma of the breast is rare. To evaluate the radiologic imaging and clinical
      appearances of this condition, the authors studied, over a 26-year period, 20
      patients (19 women) with primary lymphoma of the breast and 7 (all women) with
      secondary involvement. The right breast was affected in 14 cases. A wide spectrum
      of appearances was noted on mammography and ultrasonography, but the use of both
      techniques is indicated because lesions may be missed by either technique used
      alone.

PMID- 2001529
TI  - Minisymposium on magnetic resonance imaging.

PMID- 2001530
TI  - Portobiliary fistula: occurrence and treatment.
AB  - Portobiliary fistula is a rare complication of percutaneous biliary drainage. The
      authors report its occurrence in four patients who had multiple percutaneous
      biliary procedures. One patient was treated by simple tamponade over several
      days, the other three by temporary balloon tamponade and permanent coil
      occlusion.

PMID- 2001531
TI  - Mechanisms of contrast enhancement in magnetic resonance imaging.
AB  - The use of contrast agents has increased the sensitivity and specificity of
      magnetic resonance imaging (MRI). Contrast in MRI is multifactorial, depending
      not only on T1 and T2 relaxation rates, but also on flow, proton density and, in
      gradient-echo sequences, on the angle of the induced field. The use of contrast
      agents in MRI changes the T1 and T2 relaxation rates, producing increased signal
      intensity on T1-weighted images or decreased signal intensity on T2-weighted
      images, or both. All contrast agents produce changes in magnetic susceptibility
      by enhancing local magnetic fields. These effects are caused by interactions
      between nuclear and paramagnetic substance magnet moments, which produce
      accentuated transitions between spin states and cause shortening of T1; the
      paramagnetic substance causes accentuated local fields, which lead to increased
      dephasing and thus shortening of T2 or T2* relaxation time. The efficacy of
      shortening of T1, T2 or T2* relaxation time depends on the distance between the
      proton nucleus and the electronic field of the paramagnetic compound, the time of
      their interaction (correlation time) and the paramagnetic concentration. The MRI
      contrast agents currently in use cause shortening of T1, T2 or T2* relaxation
      time. Metal chelates (e.g., gadolinium-diethylene triamine penta-acetic acid [Gd
      DTPA]) in low concentration cause shortening of T1 relaxation times, and the
      superparamagnetics (e.g., ferrite) cause shortening of T2 relaxation times.

PMID- 2001532
TI  - Computed tomography and magnetic resonance imaging of an infiltrative lesion of
      the anterior visual pathways.
AB  - Infiltrative lesions of the optic chiasm and optic nerves are uncommon. The
      authors report such a case and discuss the differential diagnosis, paying
      particular attention to imaging. In the reported case high-resolution computed
      tomography and magnetic resonance imaging revealed thickening of the optic chiasm
      and intracranial optic nerves, a pattern characteristic of an inflammatory or
      neoplastic process.

PMID- 2001533
TI  - Don't leave home without it.

PMID- 2001534
TI  - Rationale for different chemotherapeutic and radiation therapy strategies in
      cancer management.
AB  - The two primary therapeutic strategies in cancer have been to give either
      chemotherapy and radiation therapy together or give a complete course of one
      treatment modality before starting the second. Clinical studies show that
      toxicity has been one of the major deterrents to substantial improvements in
      cancer management when the two modalities are administered together. On the other
      hand, the prolonged time necessary to administer all of one modality followed by
      the other makes it likely that repopulation of the tumor during sequential
      treatment will diminish therapeutic effectiveness. A third strategy of giving
      chemotherapy and radiation therapy has been developed. This new regimen was
      designed to give chemotherapy initially, maintain the chemotherapy schedule to
      avoid any reduction in its effectiveness, and add radiation therapy as early as
      possible in between courses of chemotherapy to minimize the development of cross
      resistance. One of the primary objectives of alternating chemotherapy and
      radiation therapy is to increase the therapeutic index by reducing toxicity
      without a significant reduction in therapeutic effectiveness. Recent clinical,
      experimental, and theoretic results with radiation therapy and chemotherapy for
      cancer management emphasize the necessity of giving both modalities with the
      greatest intensity possible in the initial phase of induction therapy. Cancer
      treatment scheduling determines the toxicity and thereby limits the dose
      intensity that can be tolerated. Scheduling may also govern the antitumor effect
      directly; however, normal host tissue makes the determination of the direct
      effects on the tumor difficult, if not impossible, in clinical studies. Well
      defined experimental solid-tumor systems provide the means for determining
      directly the relationship between toxicity and antitumor effects in relation to
      tumor burden and total therapeutic dose. In addition, its relationship to dose
      intensity and scheduling can be determined by the using more sophisticated
      research techniques, such as response surface methods. Well-defined clinical
      protocols to determine how to interact chemotherapy with radiation therapy more
      effectively hold considerable potential for rapid improvement in treatment of
      radiosensitive and chemosensitive cancers.

PMID- 2001535
TI  - 13-cis-retinoic acid in the treatment of elderly patients with acute myeloid
      leukemia. A phase II pilot study of the Eastern Cooperative Oncology Group.
AB  - The management of acute myeloid leukemia in the elderly (65 years and older) is
      unsatisfactory because of poor patient tolerance of standard myeloablative
      chemotherapy. The authors conducted a Phase II study to evaluate the
      effectiveness and toxicity of 13-cis-retinoic acid (CRA) in the therapy of
      elderly patients with acute myeloid leukemia (AML). Patients presenting with
      leukocyte counts less than 20,000/microliters were treated with CRA alone. Those
      with leukocyte counts of 20,000/microliters or greater were pretreated with
      hydroxyurea, followed by CRA. Twelve of 18 patients received at least 4 weeks of
      CRA and were thus considered evaluable for toxicity and response. No objective
      responses were observed. Cis-retinoic acid administration was well tolerated;
      only modest dermatologic, musculoskeletal, and gastrointestinal toxicity was
      observed. Alternative therapeutic strategies should be investigated in this
      subpopulation of AML patients.

PMID- 2001536
TI  - Stage IV neuroblastoma in infants. Long-term survival.
AB  - Before the advent of multiagent chemotherapy, the prognosis for patients with
      Stage IV neuroblastoma of all ages was dismal. More recently, marked improvement
      in infants with Stage IV neuroblastoma has been reported. Twenty-four infants
      with Stage IV neuroblastoma have been treated at the Dana-Farber Cancer
      Institute/The Children's Hospital, and the Joint Center For Radiation Therapy,
      Boston, Massachusetts, between 1970 and 1988. Twenty-three of these patients were
      treated with multiagent chemotherapy and one with a single drug. In the initial
      report, ten of 11 patients were alive without evidence of disease after intensive
      therapy. In this report the authors update their initial series of patients and
      include 13 additional patients who subsequently presented to our institutions
      with Stage IV neuroblastoma younger than 1 year of age. The 5-year actuarial
      event-free survival for the 24 patients is 75%. No patient without bone
      metastases died from neuroblastoma, and 12 of 16 patients with bone metastases
      remained disease free. These results confirm that infants with Stage IV
      neuroblastoma have a very good prognosis when treated with intensive multiagent
      chemotherapy.

PMID- 2001537
TI  - Intraoperative electron beam radiation therapy for recurrent locally advanced
      rectal or rectosigmoid carcinoma.
AB  - A multimodality approach of moderate-dose to high-dose preoperative radiation
      therapy, surgical resection, and intraoperative electron beam radiation therapy
      (IORT) has been used for patients with locally recurrent rectal or rectosigmoid
      carcinoma. The 5-year actuarial local control and disease-free survival for 30
      patients undergoing this treatment program were 26% and 19%, respectively. The
      most important factor predicting a favorable outcome was complete resection with
      negative pathologic resection margins. The determinant local control and disease
      free survival for 13 patients undergoing complete resection were 62% and 54%,
      respectively, whereas for 17 patients undergoing partial resection these figures
      were 18% and 6%, respectively. There did not appear to be a difference in local
      control or survival based on the original surgical resection (abdominoperineal
      resection versus low anterior resection). However, the likelihood of obtaining a
      complete resection after preoperative radiation therapy was higher in patients
      who had previously undergone a low anterior resection than patients undergoing
      prior abdominoperineal resection. For the 30 patients undergoing external beam
      irradiation, resection, and IORT, the most significant toxicities were soft
      tissue or sacral injury and pelvic neuropathy. Efforts to further improve local
      control are directed toward the concurrent use of chemotherapy (5-fluorouracil
      with and without leucovorin) as radiation dose modifiers during external beam
      irradiation and the use of additional postoperative radiation therapy.

PMID- 2001538
TI  - A pilot study of suramin in the treatment of metastatic renal cell carcinoma.
AB  - Suramin sodium is an aromatic polysulfonated compound that was originally
      introduced as an antiparasitic agent in the 1920s. Recently, in view of its
      ability to bind and disrupt the function of multiple growth factors and cellular
      enzyme systems, the authors have been evaluating the role of suramin as an
      antitumor agent. In this study, 12 patients with metastatic renal cell carcinoma
      received parenteral suramin by continuous infusion to a peak plasma suramin level
      greater than 200 micrograms/ml. No objective radiographic responses were
      observed, although greater than 90% necrosis of multiple tumor sites was
      documented at autopsy in one patient and normalization of tumor-related
      hypercalcemia occurred in another patient. Two patients had stable disease of 10
      and 28 weeks' duration, respectively. Significant toxicities included hypotension
      related to sepsis and resulting in renal insufficiency (one patient), development
      of liver function abnormalities (one patient) marked thrombocytopenia (one
      patient), prothrombin time prolongation (all patients), vortex keratopathy (two
      patients), and Grade 1 sensory neuropathy (two patients). On the basis of the
      current results, suramin does not appear to be an active single agent against
      metastatic renal cell carcinoma when administered by this dosing schedule.

PMID- 2001539
TI  - High-dose cisplatin plus dacarbazine in the treatment of metastatic melanoma.
AB  - The combination of cisplatin plus dacarbazine (DTIC) is active in metastatic
      melanoma with response rates reported between 10% and 55%. To optimize this
      regimen, a Phase II study was conducted employing a dose intensity of cisplatin
      higher than previously reported. Twenty-two patients were treated. Eight patients
      received cisplatin 100 mg/m2 on days 1 and 8 combined with DTIC 300 mg/m2 on days
      1, 2, 8 and 9 (regimen A). Because of excessive toxicity, the protocol was
      modified so that cisplatin was given at 50 mg/m2 per day and DTIC 350 mg/m2 per
      day on days 1 through 3 (regimen B). The overall response rate was 32% and
      consisted of four partial and three complete responses (CR). The median duration
      of response was 6 months. Two of the CR remain in sustained, unmaintained
      remission in excess of 1.5 years. All seven patients that responded were treated
      on regimen B. High-dose cisplatin plus DTIC on a 3-day schedule represents an
      effective, well-tolerated therapy for metastatic melanoma.

PMID- 2001540
TI  - Prognostic factors for survival of patients with advanced urothelial tumors
      treated with methotrexate, vinblastine, doxorubicin, and cisplatin chemotherapy.
AB  - Between February 1983 and February 1986, 132 patients with advanced urothelial
      tract tumors were treated with methotrexate, vinblastine, Adriamycin
      (doxorubicin), and cisplatin (M-VAC) chemotherapy. Analysis of prognostic factors
      for survival of the first 92 patients was undertaken using the Cox proportional
      hazards model. Normal alkaline phosphatase and high Karnofsky performance status
      (KPS) were predominant for long survival. Patients 60 years or older at
      initiation of therapy were likely to survive longer than younger patients,
      perhaps indicating physician selectivity of older patients for this therapy, and
      those with initial hemoglobin in the normal range were also likely to survive
      longer. The additional 40 patients' data were used to validate the model.
      Clinical implications of the prognostic factors are discussed.

PMID- 2001541
TI  - Results of radiation therapy in carcinoma of the base of the tongue. The Curie
      Institute experience with about 166 cases.
AB  - Between 1960 and 1980, 166 patients with squamous cell carcinoma of the base of
      the tongue were treated with primary irradiation at the Curie Institute (Paris,
      France). Distribution according to the TNM system 1978 International Union
      Against Cancer (UICC) was the following: 22 T1 lesions, 47 T2 lesions, 64 T3
      lesions, and 33 T4 lesions. Regional nodes were not palpable in 50 cases, 35 had
      N1 nodes, 12 had N2 nodes, and 69 had N3 nodes. All patients received external
      beam radiation. The 2-year, 3-year, and 5-year overall survival rates for all
      patients were, respectively, 45%, 37%, and 27%. Local control was significantly
      related to the initial status of the primary, to the tumor regression at the end
      of the radiation therapy, and to the histologic differentiation. The 2-year local
      control was 96% for T1 lesions, 57% for T2 lesions, 45% for T3 lesions, and 23%
      for T4 lesions. Local control was 70% if the tumor regression was complete at the
      end of the treatment and 27% if the tumor regression was partial. No significant
      differences were found in primary local control with respect to degree of
      infiltration, age, and dose of radiation therapy over a dose of 60 Gy in 6 weeks.
      The 3-year regional control was 86% for N0, 78% for N1, and 60% for N2 and N3.
      Among the tumor characteristics analyzed, the most useful ones for predicting
      local control and survival were clinical tumor staging parameters and tumor
      radiation-induced regression. A new therapeutic approach based on the evaluation
      of the tumor regression at 50/55 Gy is under discussion.

PMID- 2001542
TI  - Radiation apoptosis of serous acinar cells of salivary and lacrimal glands.
AB  - Xerostomia and xerophthalmia are common and potentially serious local side
      effects of radiotherapy for head and neck cancer. Clinical observations supported
      by experimental findings show that radiation, even in low doses, causes acute
      diminutions of saliva and tears by rapidly killing the serous cells of the
      salivary and lacrimal glands, respectively. Serous acini of salivary and lacrimal
      glands have similar developmental, morphologic, and functional characteristics.
      Serous acinar cells are functionally mature, secretory epithelial cells that
      normally do not divide and are long lived. Irradiation of the salivary and
      lacrimal glands of rhesus monkeys resulted in selective death of serous acinar
      cells within 24 hours. The paradigm for acute radiation seroadenosis is
      intermitotic or interphase cell death caused by apoptosis.

PMID- 2001543
TI  - 18F-2-deoxy-2-fluoro-D-glucose uptake into human tumor xenografts. Feasibility
      studies for cancer imaging with positron-emission tomography.
AB  - The positron-emitting glucose analogue 18F-2-fluoro-2-deoxy-d-glucose (FDG) was
      evaluated for its accretion into the following subcutaneous human tumor
      xenografts in nude mice: B-cell lymphoma (Namalwa or Raji), ovarian carcinoma
      (HTB77), colon cancer (SW948), choriocarcinoma (BEWO), bladder cancer (UM-UC-2),
      renal cell carcinoma (UM-RC-3), neuroblastoma (Mey), melanoma (HTB63), and small
      cell lung carcinoma (NCI69). Two hours postinjection, tumor uptakes ranged from
      0.027 (colon cancer) to 0.125% kg injected dose/g (melanoma); and was greater
      than 0.085 in the Namalwa lymphomas and the renal cell carcinomas. Tumor-blood
      ratios of up to 23:1 were seen 2 hours postinjection (melanoma) with a mean tumor
      blood ratio for all tumors of 12.3 +/- 1.8. Uptake in the other tumors was
      intermediate. When evaluated, tumor uptake was slightly greater at 1 than at 2
      hours postinjection, although target-background ratios were generally higher at 2
      hours postinjection. This compound, FDG, may have broad applicability as a tracer
      for positron-emission tomographic imaging of many human malignancies.

PMID- 2001544
TI  - Detection of somatic DNA alterations in ovarian cancer by DNA fingerprint
      analysis.
AB  - The M13 phage single-strand DNA probe which recognizes highly polymorphic loci
      was applied to HinfI-digested DNA isolated from tumor tissue and peripheral
      leukocytes from 20 patients with ovarian cancer. An average of 22 minisatellite
      containing DNA fragments were observed per individual. DNA fingerprint analysis
      revealed a change in restriction-fragment-length patterns in the DNA from 12 of
      20 (60%) tumors compared with the patient's constitutional DNA. Deletion of one
      or more bands from the tumor was recognized by the probe in seven cases, new
      bands were identified in two, and intensity shift was demonstrated in eight. The
      authors conclude that the unmapped M13 minisatellite probe is a useful method for
      identifying cancer-related somatic DNA alterations.

PMID- 2001545
TI  - Stimulation of tumor cell growth by vasoactive intestinal peptide.
AB  - Vasoactive intestinal peptide (VIP) stimulated the growth of murine Lewis lung
      carcinoma cells in culture. The growth promoting effect was dependent on the
      concentration of VIP. Exposure to VIP for 12 hours followed by removal of the
      peptide resulted in sustained growth promotion for 4 to 5 days in culture.
      Synthetic fragments of VIP, i.e., VIP (1-16) and VIP (22-28), and the unrelated
      peptide neurotensin failed to stimulate the growth of the Lewis lung carcinoma
      cells. The growth-promoting effect of VIP was also observed in a murine mammary
      tumor cell line and a human lung adenocarcinoma cell line.

PMID- 2001546
TI  - Association of interleukin-2 therapy with staphylococcal bacteremia.
AB  - The authors prospectively monitored patients undergoing leukapheresis for
      peripheral stem cell harvesting (PSCH) or lymphokine activated killer (LAK) cell
      generation for 3 weeks after catheter placement for evidence of local or systemic
      infections. Over a 1-year period, 16 patients underwent leukapheresis for PSCH in
      preparation for autologous bone marrow transplantation (ABMT). The original
      catheters remained in place an average of 20 days without any documented
      infections. Seventeen patients underwent leukapheresis as part of a low-dose
      interleukin-2 (IL-2) treatment for LAK cell generation, and their catheters
      remained in place an average of 20.2 days with three documented episodes of
      bacteremia (18%). Eight patients treated with high-dose IL-2 also underwent
      leukapheresis for LAK cell generation and their catheters remained in place an
      average of 12 days with three documented episodes of bacteremia (38%). In all
      cases of bacteremia, Staphylococcus species were isolated from the blood. The IL
      2 exposure level was associated with the risk of bacteremia (P = 0.01). Other
      potential risk factors (e.g., number of pheresis procedures, complement level,
      serum immunoglobulin levels, absolute neutrophil count) were not related to this
      risk.

PMID- 2001547
TI  - Tissue distribution of 2-3 and 2-6 sialyl Lewis A antigens and significance of
      the ratio of two antigens for the differential diagnosis of malignant and benign
      disorders of the digestive tract.
AB  - The authors investigated the tissue distribution of two kinds of sialylated
      derivatives of Lewis A (Le(a)) antigen in patients with cancers of the digestive
      system using specific monoclonal antibodies, and evaluated the significance of
      determining the 2-3 and 2-6 sialylated Le(a) antigen levels for the diagnosis of
      cancer. In most specimens from patients with cancers of the pancreas, biliary
      tract, stomach, and colon, the 2-3 sialylated Le(a) antigen was strongly
      expressed in cancer cells. However, 2-6 sialylated Le(a) antigen was less
      frequently expressed in cancer cells. The former is therefore more specific to
      cancer than the latter. Also, the serum level of the 2-3 sialylated Le(a) antigen
      was significantly higher than that of the 2-6 counterpart in patients with
      cancers of pancreas, biliary tract, stomach, and colon. The resulting ratio of
      serum 2-3/2-6 sialylated Le(a) antigens was frequently high in patients with
      malignancy and was low in patients with benign disorders of these digestive
      organs. Therefore, the 2-3/2-6 sialylated Le(a) antigen ratio is a useful for the
      differential diagnosis of malignant disorders in these organs. However, liver
      disorders were found to be exceptional in that both antigens were mostly absent
      in hepatocellular carcinoma (HCC) cells in immunohistologic examination, as well
      as in nonmalignant parenchymal liver cells. Only the epithelial cells of the
      intrahepatic bile ducts expressed the 2-6 sialylated Le(a) antigen strongly, and
      expressed the 2-3 sialylated Le(a) antigen moderately. The levels of both
      antigens were sometimes high in patients with liver disorders, but the ratio
      always remained low in patients with HCC as well as benign liver disorders such
      as cirrhosis or chronic hepatitis. The sialylated Le(a) antigens, which sometimes
      accumulate in the sera of patients with HCC, were concluded to originate from the
      epithelial cells of the proliferating small bile ducts, and those serum antigens
      cannot be considered as evidence for the presence of liver cancer cells.

PMID- 2001548
TI  - Establishment and characterization of unique cell lines (KCC-1a and KCC-1b) from
      endometrial adenocarcinoma with clear cell carcinoma presenting unusual
      karyotypes and estrogen secretion.
AB  - Human endometrial adenocarcinoma cell lines (KCC-1a and KCC-1b) were established
      from a resected endometrial carcinoma of a 67-year-old woman. The original tumor
      showed the bimorphic patterns of tubular adenocarcinoma and clear cell carcinoma.
      The cell lines have been maintained for 50 months through 100 passages. The
      doubling time of KCC-1a was 87 hours, whereas that of KCC-1b was 144 hours. The
      number of chromosomes of KCC-1a distributed in a range from 33 to 79, whereas
      that of KCC-1b distributed in a range from 64 to 82 (mode, 76). Functionally,
      both KCC-1a and KCC-1b cells showed the productions of estrone (E1) and estradiol
      (E2) but not estriol (E3) or progesterone (P). These cells grown in a serum-free
      medium secreted E1 (KCC-1a, 13.6 pg/ml; KCC-1b, 9.5 pg/ml) and E2 (10.5 pg/ml,
      9.5 pg/ml) at passage 40. Neither KCC-1a nor KCC-1b cells contained estrogen or
      progesterone receptors. Tumor markers--alpha-fetoprotein, carcinoembryonic
      antigen, CA 125, and CA 19-9--were not detected. Both KCC-1a and KCC-1b cells
      produced tumors in nude mice xenografts. Histologically, the tumors of KCC-1a
      cells were clear cell carcinoma, whereas those of KCC-1b cells were tubular
      adenocarcinoma. These findings suggest that KCC-1a and KCC-1b cells will provide
      useful information to clarify the histogenesis of endometrial carcinoma combined
      with clear cell carcinoma.

PMID- 2001549
TI  - Immunohistologic localization of alpha, mu, and pi class glutathione S
      transferases in human tissues.
AB  - Human alpha, pi, and mu class glutathione S-transferases (GSH S-T) have been
      localized immunohistologically in a variety of organs. Alpha GSH S-T are found
      principally in hepatocytes, proximal convoluted tubules of kidney, the deep
      reticular layer of the adrenal gland, interstitial cells of the testis, and
      oxyntic cells of the stomach. The pi GSH S-T are present in relative abundance in
      ductular, as opposed to parenchymal cells in the liver, pancreas, salivary
      glands, and kidney. The presence of mu GSH S-T in the tissues of certain patients
      and its absence in the same tissues from other patients has been demonstrated.
      The pi GSH S-T seems to be most persistently and strongly expressed in tumors but
      alpha GSH S-T are also found in some neoplasms whereas the mu GSH S-T are
      occasionally present when the other two transferases are weak or absent.

PMID- 2001550
TI  - Human immunodeficiency virus-associated Hodgkin's disease. Clinicopathologic
      studies of 24 cases and preponderance of mixed cellularity type characterized by
      the occurrence of fibrohistiocytoid stromal cells.
AB  - Hodgkin's disease (HD) was diagnosed in 24 patients who were either seropositive
      for human immunodeficiency virus (HIV) (21) or members of a high-risk group
      (three), but had not developed acquired immune deficiency syndrome (AIDS).
      Clinical presentation of the disease was characterized by constitutional symptoms
      in all, especially fever (23/24) and disseminated disease (22/24) at diagnosis.
      Mediastinal adenopathy was rare. Bone marrow involvement was particularly
      frequent (12/24), and a positive bone marrow biopsy preceded lymph node biopsy in
      5 of the 12. Histopathologic features of these tumors included an increased
      number of nonlymphoid stromal cells, i.e., histiocytic and/or fibroblastoid. In
      some tumors these fibrohistiocytoid stromal cells were arranged in bundles, but
      distinct nodule with birefringent collagen band formation was not observed.
      Twenty-two patients were treated, most with combination chemotherapy; one was
      untreated; one, unknown. Sixteen, including the one untreated, died with disease
      at 3 to 25 months; one died of an unrelated cause; four were alive at 3 to 24
      months; three were lost to follow-up. Frequent bone marrow involvement at
      presentation suggests the usefulness of the bone marrow biopsy for diagnosis in
      subjects at risk, especially when they present with spiking fever of unknown
      origin. Contrary to most previous series, virtually all of our cases were of
      mixed cellularity type, characterized by increased fibrohistiocytoid stromal
      cells in place of depleting lymphocytes. The classic nodular sclerosing feature
      with birefringent collagen band formation was not observed. In conclusion, HIV
      associated HD was characterized by advanced stage with fever at presentation,
      preponderance of mixed cellularity histologic type with increased
      fibrohistiocytoid stromal cells, and poor outcome. Hodgkin's disease in AIDS
      patients presents an intriguing biological model to study the role of stromal
      histiocytes in immunodeficient patients.

PMID- 2001551
TI  - Lymph nodes in incipient adult T-cell leukemia-lymphoma with Hodgkin's disease
      like histologic features.
AB  - Lymph nodes were examined from four patients with incipient adult T-cell leukemia
      lymphoma (ATLL) who had mild lymphadenopathy, fatigue, no or a few atypical
      lymphocytes in their peripheral blood, and integrated proviral human T-cell
      lymphotrophic virus type I (HTLV-I) DNA in the nodes. The HTLV-I DNA was detected
      by southern blot analysis and/or polymerase chain reaction in the lymph nodes of
      all cases. The nodal architecture was preserved. Some scattered or aggregated
      highly lobular, cerebriform, or Reed-Sternberg-like giant cells were observed,
      with occasional mitoses and diffuse infiltration of small to medium-sized
      lymphocytes, with no or minimal nuclear abnormalities in the enlarged paracortex.
      The giant cells were usually positive for Ki-1 and also for UCHL-1 and other T
      cell markers but negative for Ber-H2. Rearrangement and/or deletion of T-cell
      receptors were found in three of four patients. All patients died within 2 years,
      with transformation to overt leukemia-lymphoma occurring in three patients, and
      pulmonary carcinoma in one. The incipient or prelymphomatous phase of ATLL should
      be differentiated from Hodgkin's disease because of the distinctly different
      prognoses of these two diseases.

PMID- 2001552
TI  - Correlation between bromodeoxyuridine-labeling indices and patient prognosis in
      cerebral astrocytic tumors of adults.
AB  - Bromodeoxyuridine (BUdR), a nonradioactive thymidine analogue, is taken up by
      cells in S-phase, and the ratio of BUdR-positive nuclei to the total number of
      cells counted is defined as the labeling index (LI). In this study, BUdR LI and
      the clinical course of 50 cerebral astrocytic tumors in adults were analyzed. The
      obtained LI distributed continuously in a broad range from 0% to 19%. The mean LI
      of 28 glioblastomas, 12 anaplastic astrocytomas, and ten astrocytomas were 8.5%,
      4.2%, and 1.2%, respectively, and these differences were statistically
      significant (P = 0.05). In the analysis of LI and the recurrence-free period
      (RFP), regardless of the histologic findings, 23 patients with LI more than 5%
      had a median RFP of 9.0 months; the median RFP of nine patients with LI of 3% to
      5% was 14.7 months. Nine of 13 patients with LI less than 3% have not yet
      recurred after a median follow-up of 36 months. These differences were also
      statistically significant by the generalized Wilcoxon test (P = 0.05). The
      proliferative potential reflected by the BUdR LI is a good clinical indicator for
      predicting the rate of tumor growth in cerebral astrocytic tumors. In combination
      with histologic diagnosis, BUdR LI could help in determining a patient's
      prognosis more precisely.

PMID- 2001553
TI  - Association between DNA ploidy pattern and cellular atypia in colorectal
      carcinomas. A new clinical application of DNA flow cytometric study?
AB  - Fresh tissue specimens from 406 colorectal carcinomas were analyzed by DNA flow
      cytometric study, and the DNA ploidy pattern was compared with Dukes' stage,
      histologic grade, and degree of cellular atypia. Sixty-one percent of the
      carcinomas had a distinct aneuploid DNA pattern. The proportion of aneuploid
      carcinomas was significantly higher in the advanced Dukes' stages than in the
      localized ones. A highly significant association was found between DNA ploidy
      pattern and degree of cellular atypia, whereas no association was demonstrated
      between DNA ploidy pattern and histologic grade. This finding might indicate that
      cellular atypia has a stronger prognostic impact than the growth pattern of the
      tumor. The authors suggest that flow cytometric DNA quantification may replace
      assessment of cellular atypia in the histologic evaluation. Furthermore, together
      with earlier findings by others, these results indicate that the degree of
      cellular atypia may be conserved during the development from adenomas to
      carcinomas.

PMID- 2001554
TI  - Langerhans cell histiocytosis of the female genital tract.
AB  - Langerhans cell histiocytosis (LCH) of the female genital tract is rare. Four new
      cases are reported, and there is a review of the 38 cases in the literature. This
      disease may involve the vulva, vagina, cervix, endometrium, and ovary. Four
      distinct patient groups, segregated on the basis of initial presentation and
      subsequent anatomic extent of disease, were categorized as follows: (1) "pure"
      genital LCH, (2) genital LCH with subsequent multi-organ involvement, (3) oral or
      cutaneous LCH with subsequent genital and multi-organ involvement, and (4)
      diabetes insipidus with subsequent genital and multi-organ disease. Although
      involvement of the genital tract can occur at any age, it is most common in young
      adulthood. Clinically, LCH may mimic either primary neoplasia or various
      inflammatory lesions; the major pathologic differential diagnosis is venereal and
      other inflammatory diseases. The pure genital form may have a distinct nosologic
      position in the spectrum of LCH similar to the "pure," self-limited cutaneous
      histiocytosis seen in infants. There is no correlation between histologic
      findings and the outcome of the genital lesions. There is also no correlation
      between clinical presentation and/or the extent of involvement and outcome of
      genital lesions; complete regression, partial improvement, persistent lesions,
      and recurrences were seen in all four groups of patients. The treatment of
      genital LCH is not well defined and is highly individualized. Therapy has
      included surgery, radiation, topical corticosteroids, topical nitrogen mustard,
      systemic chemotherapy, and combination therapy; mixed results were obtained with
      all treatment modalities. Although no modality has been shown to yield a superior
      outcome, complete surgical excision is advocated as initial therapy.

PMID- 2001555
TI  - The relationship of ABH(O) blood group antigen expression in intraepithelial
      dysplastic lesions to clinicopathologic properties of associated transitional
      cell carcinoma of the bladder.
AB  - Paraffin-embedded, giant-step sections of 13 bladders with transitional cell
      carcinomas were stained with monoclonal anti-A or anti-B antibodies to
      investigate whether intraepithelial dysplastic lesions are related to obvious
      tumors. Normal and/or hyperplastic lesions were retained in only eight bladders;
      severe dysplasia and/or carcinoma in situ were found in all bladders except two.
      AB-antigen expression was retained in intraepithelial lesions of bladders with
      invasive carcinoma. Most intraepithelial lesions were AB-antigen negative in
      bladders with frequently recurrent tumors. In bladders with initially multiple
      tumors, AB-antigen expression was negative in almost one half of the
      intraepithelial lesions. Therefore, it appears likely that most multiple or
      recurrent bladder carcinomas arise from dysplastic cells in intraepithelial
      lesions which have acquired malignant potential; initially invasive tumors
      quickly develop from a limited lesion acquiring a high malignant potential
      without changes of cell phenotype in most intraepithelial lesions.

PMID- 2001556
TI  - The relationship of nasopharyngeal carcinomas and second independent malignancies
      based on the Radiation Therapy Oncology Group experience.
AB  - The authors sought to learn if the incidence of second independent malignancies
      after the irradiation of carcinomas of the nasopharynx is similar to that
      observed after treatment of tumors arising in other head and neck sites. One
      hundred twenty-one patients who had primary carcinomas of the nasopharynx who
      were treated solely by ionizing radiation (according to the specifications of a
      Radiation Therapy Oncology Group protocol) were identified and their subsequent
      well-being was reviewed. Overall there was a 4.1% incidence of second
      malignancies (2% after 3 years, 5% after 5 years, and 8% after 8 years) with most
      arising in the upper aerodigestive tract. This rate is significantly less than
      the rate associated with other head and neck sites. It is not significantly
      different from the rate of first malignancies observed in an age-matched and sex
      matched population. When only those patients who were free of all evidence of
      neoplastic disease 6 months after the completion of radiotherapy are considered,
      similar analysis leads to similar outcomes. The authors conclude that the risk of
      second malignancies after the successful irradiation of carcinomas of the
      nasopharynx is substantially less than after treatment of tumors at other head
      and neck sites.

PMID- 2001557
TI  - Thermography as a predictor of prognosis in cancer of the breast.
AB  - Although thermography is generally considered to lack sufficient sensitivity to
      be a useful in diagnosis of cancer of the breast, the association of a thermal
      abnormality with some breast cancers cannot be discounted. Breast cancers
      demonstrating such a thermographic abnormality have been reported to be
      associated with decreased survival when compared with patients with no such
      change. In a study of 214 patients confirmed to have breast cancer without
      distant metastases, 121 were found to have a thermographic abnormality. Patients
      whose tumors were thermographically abnormal had significantly larger primary
      lesions and a higher proportion of metastatic axillary lymph nodes. However, both
      the 5-year survival and the 5-year disease-free survival were not significantly
      different from patients who had no thermographic abnormality.

PMID- 2001558
TI  - Depression of serum melatonin in patients with primary breast cancer is not due
      to an increased peripheral metabolism.
AB  - Serum melatonin and its main metabolic product 6-sulfatoxymelatonin were
      determined in 17 patients with breast cancer (BC) with either a fresh primary
      tumor (nine) or a secondary tumor (eight) as well as in four patients with
      untreated benign breast disease (controls). Circadian rhythms were detected in
      all groups with acrophases around 2 AM for melatonin and around 3 AM for 6
      sulfatoxymelatonin. The nocturnal melatonin and 6-sulfatoxymelatonin
      concentrations were significantly depressed in the group of patients with primary
      breast cancer compared with controls (P less than 0.01, P less than 0.025). The
      circadian amplitudes of melatonin and 6-sulfatoxymelatonin were also depressed by
      81% (P less than 0.01) and 63% (P less than 0.01). In contrast, patients with
      secondary BC had nocturnal melatonin and 6-sulfatoxymelatonin concentrations and
      amplitudes similar to controls. These results demonstrate that the depression of
      circulating melatonin in patients with primary BC is not due to an enhanced
      degradation to 6-sulfatoxymelatonin in the liver but must be due to a reduced
      activity of the pineal gland.

PMID- 2001559
TI  - Meningeal carcinomatosis in breast cancer. Prognostic factors and influence of
      treatment.
AB  - In 58 breast cancer patients with meningeal carcinomatosis (MC) pretreatment
      characteristics, clinical course, and response to treatment were evaluated. Forty
      four patients were uniformly treated with intraventricular chemotherapy. Fourteen
      patients did not receive intraventricular treatment. In the intraventricularly
      treated group the median survival was 12 weeks. Multivariate analysis of the
      pretreatment characteristics of the intraventricularly treated patients
      demonstrated a prognostic significance with respect to survival for age older
      than 55 years, lung metastases, cranial nerve involvement, cerebrospinal fluid
      (CSF) glucose less than 2.5 mmol/l, and CSF protein 0.51 to 1.0 g/l. Based on the
      significance of these predicting factors a prognostic index (PI) identified four
      groups of patients with a median survival of 43 weeks, 22 weeks, 11 weeks, and 3
      weeks, respectively. After 6 weeks of intraventricular treatment 22 patients
      showed a neurologic improvement or stabilization, and nine patients showed a
      worsening of the neurologic signs, whereas 13 patients (30%) had already died.
      The responders had a median additional survival of 5 months versus 1 month for
      nonresponders. No relation was found between survival and intensity of the
      intraventricular treatment after the first 6 weeks of treatment. Almost all long
      survivors had also received systemic treatment for systemic disease, whereas most
      patients who died within 6 months did not receive systemic therapy. Radiation
      therapy had no influence on the survival time. Early death due to the intensive
      treatment occurred in three patients. In 11 of the 17 patients who survived more
      than 4 months an often seriously debilitating late neurotoxicity developed. The
      survival curve of the nonintraventricularly treated patients appeared to be
      essentially the same as the curve of the intraventricularly treated patients.
      Using the same PI the predicted survival time was also the same as in the
      intraventricularly treated group. It is concluded that survival in MC from breast
      carcinoma may be more dependent on some pretreatment characteristics than on
      treatment intensity. On the basis of these pretreatment characteristics the
      survival time seems to be predictable. Finally, late neurotoxicity due to
      aggressive treatment leads to impairment of the quality of life in more than 50%
      of the long survivors. The exact value of intraventricular and systemic therapy
      in patients with MC still has to be determined.

PMID- 2001560
TI  - Clinical observation on the association of gallstones and colorectal cancer.
AB  - A possible association between gallstones, colorectal cancer, and gastric cancer
      was investigated. The age distribution and mean age of the two cancer groups were
      identical. The incidence of gallstones in 378 colorectal cancer cases and 869
      gastric cancer cases was 7.1% and 5.5%, respectively. Of colorectal cancer cases,
      33 cases with multiple carcinomas had a significantly higher gallstone incidence
      than cases with a solitary carcinoma--24.2% and 5.5%, respectively. The mean age
      was 5 years older in gallstone cases than in those without gallstones in both
      cancer groups, and it was 4 years older in multiple-carcinoma cases than in
      solitary-carcinoma cases in the colorectal cancer group. These results suggest
      that the higher levels of same causative factors (i.e., dietary fat) are
      associated with a longer duration of gallstone formation and colorectal cancer
      development as demonstrated by multiple colorectal-carcinoma cases.

PMID- 2001561
TI  - Sunlight and dysplastic nevus risk. Results of a clinic-based case-control study.
AB  - The dysplastic nevus (DN) is the most important risk factor and precursor for
      malignant melanoma. The authors compared the responses of 132 consecutive cases
      of DN, 186 consecutive cases of cutaneous melanoma, and 239 controls attending
      the same subspecialty clinic to questions regarding sun sensitivity, sun
      exposure, and other possible risk factors. Dysplastic nevus cases were younger
      than controls and were of a higher social class, as indicated by more years of
      formal education. Sun sensitivity (assessed by reported depth of tan after
      multiple exposures) was associated with both DN risk and melanoma risk after
      controlling for age and education in logistic regression analysis (P = 0.009 and
      0.03, respectively), but for DN risk this association was nonlinear: the relative
      risks (versus deep tan) were 2.3 for average tanners, 2.8 for light tanners, and
      1.6 for those who reported practically no tan. Sun exposure measures were not
      associated with DN risk after controlling for age and education, whether or not
      depth of tan was controlled in the analysis. These observations suggest a role
      for either sunlight or a trait linked with sun sensitivity in the development of
      dysplastic nevi.

PMID- 2001563
TI  - American Cancer Society National Conference on Cancer and the Changing Healthcare
      System. San Francisco, California, May 3-5, 1990.

PMID- 2001562
TI  - Serum ferritin and stomach cancer risk among a Japanese population.
AB  - Using stored serum samples collected during from 1970 to 1972 and/or 1977 to 1979
      from a fixed population in Hiroshima and Nagasaki, Japan, serum ferritin,
      transferrin, and ceruloplasmin levels were determined immunologically for persons
      in whom stomach (233 cases) or lung cancer (84 cases) subsequently developed as
      well as for their controls. An elevated stomach cancer risk was associated with
      low antecedent serum ferritin levels, with more than a threefold excess among
      those in the lowest compared with the highest ferritin quintile. The risk did not
      vary with the time between blood collection and stomach cancer onset, remaining
      high among those with low ferritin levels 5 or more years before cancer
      diagnosis. Achlorhydria, diagnosed in a sample of the population about 10 years
      before the 1970-to-1972 blood collection and up to 25 years before cancer, was an
      independent marker of stomach cancer risk. In combination, low serum ferritin and
      achlorhydria were associated with a tenfold increase in the subsequent risk. No
      effect of transferrin or ceruloplasmin, independent of ferritin, was observed in
      the gastric cancer risk, and the risk of lung cancer was not related to these
      three serum proteins. These prospective findings indicate that biologic markers
      of an increased risk of stomach cancer can be detected long before cancer onset.

PMID- 2001564
TI  - The human costs of cancer and the response of the National Cancer Program.
AB  - The three foundations of the National Cancer Program are basic research, clinical
      trials (in prevention and treatment), and cancer centers. These foundations have
      supported a great deal of progress against cancer over the past 20 years.
      Nevertheless, a number of challenges remain, and continued progress will depend
      on the speed with which research advances can be translated into practical
      realities. Poverty is a risk factor for cancer incidence and mortality. Thus, a
      lack of access to the technologies generated by the National Cancer Program can
      be a force for bringing about differential burdens of cancer in underserved
      populations.

PMID- 2001565
TI  - Changing cancer care in the 1990s and the cost.
AB  - Progress in cancer research in the 1980s has led to predictions of a technologic
      explosion in the 1990s. Yet, with this progress there has been a groundswell of
      protest at the rapidly escalating costs of health care. More than $600 billion
      was spent on health care in 1989 and estimates of $1.5 trillion are made for the
      year 2000. Repeated attempts at cost containment have failed. It has been
      suggested that only by retarding technologic advances will we be able to control
      costs. Many observers believe that rationing of health care is the only solution,
      but new technology not only improves cancer care, it often decreases cost. It is
      not rational to retard advances that may later reduce costs, nor is it humane to
      retard advances that improve care, even if they cost more. In identifying
      priorities we should begin with the principle that treatments be restricted to
      clinical trials unless they have been demonstrated to prolong survival or improve
      the quality of life. If the payers reimburse procedures in an investigative
      setting, they will be on firm ground when they deny support for those same
      procedures outside an investigative setting. This is both an ethical and a
      fiscally responsible position for the third parties to take. It will not be easy
      for the profession or for the payers to deal with these problems. Public
      education and patient education will be key elements of any solution. Shifting
      the blame from politician to payer to professional will only make the problems
      worse.

PMID- 2001566
TI  - Forces of change in the health care system. Implications for cancer care in the
      1990s.
AB  - Dramatic changes will occur in the health care system during the 1990s which will
      profoundly affect the delivery of care for cancer. Perhaps the most important
      factor is the aging of the population. As the proportion of people who achieve
      old age increases, the absolute prevalence and incidence of cancer will increase
      despite improved treatment techniques. This phenomenon will increase health care
      expenditures despite ongoing efforts to control costs. Second, there will be
      continuing efforts at cost control and increased emphasis on quality assurance
      and outcomes by third party payers. Providers will be scrutinized and compared
      with one another. The large payers of the nation's health care bills will demand
      proof of outcome and cost leading to bidding by providers and payment only to
      those who have the best outcome for the least money. Third, there will be an
      increasing emphasis on prevention and screening, in public health policy, an
      approach that may conflict with personal freedom. Fourth, there will be
      increasing deliberations and questions about the ethics of the health care system
      and treatment decisions. There will be continuing debate about the need for a
      rationing of health care and the right of individual privacy versus the states'
      right to preserve life. These changes will impact on all health care
      professionals whose practice includes patients with cancer.

PMID- 2001567
TI  - Legislative influences on cancer care.
AB  - Deficit reduction politics was a major force in policymaking in the 1980s and a
      pervasive fact of life in the development of health policy. The Medicare budget
      was habitually used to find savings for deficit reduction and reforms, such as
      how to address the problem of 31 to 37 million uninsured Americans, were
      postponed. The 101st Congress did produce major physician payment reforms and in
      the spring of 1990, the Pepper Commission issued its recommendations for access
      to care and long-term care. Less sweeping but significant proposals affecting
      cancer care were considered by Congress. For example, positive actions were taken
      on anti-smoking and food labeling proposals. Funding for the National Institutes
      of Health was increased, and there was a growing awareness of the threat to
      biomedical research presented by assaults on animal research facilities.

PMID- 2001568
TI  - Access to cancer prevention, detection, and treatment.
AB  - The American Cancer Society Hearings on Cancer and the Poor made visible to the
      nation the harsh realities and consequences of lack of access to health care
      among the poor and uninsured in America. Access to care is more than mere
      availability; it is also financial accessibility, effectiveness, acceptability,
      appropriateness, and comprehensiveness of care. The problems and consequences of
      lack of health care access and its impact on the cancer problem among poor
      Americans are explored, and ways practitioners and public advocates can improve
      access are suggested. Local communities have risen to action to make health care
      more accessible. Successful programs have done their research to document access
      problems; then they have taken their findings to county governments to request
      additional funding and to health care institutions to request institutional
      policy and service changes to make health care more available and accessible.

PMID- 2001569
TI  - Adjuvant therapy for node-negative breast cancer. The use of prognostic factors
      in selecting patients.
AB  - Patients with invasive breast cancer and pathologically negative lymph nodes (NO)
      have a favorable 10-year survival rate, particularly with small (less than 1 cm)
      primary tumors. Overall, however, 20% to 35% will experience recurrence with
      local therapy only. Adjuvant chemotherapy or tamoxifen have prolonged disease
      free survival (DFS), but not overall survival (OS). Unanswered questions of
      optimal end point (DFS or OS) and the risk of treating many to benefit few have
      prompted clinicians to use prognostic indicators to facilitate treatment
      recommendations. Currently, the most readily available and accurate information
      comes from TNM staging, pathologic features, and hormone receptors. Ploidy, S
      phase fraction, HER-2-neu amplification or over-expression, and cathepsin-D may
      be useful prognostic indices. Until a more precise system of weighing several
      prognostic variables is developed, the decision to recommend adjuvant systemic
      therapy in this generally good prognosis group will have to be thoughtfully
      considered by patient and physician. Whenever possible, patients should be
      encouraged to enter clinical trials.

PMID- 2001570
TI  - The role of chemotherapy for node-negative breast cancer.
AB  - Approximately 25% of women with early stage breast cancer and negative axillary
      nodes will eventually die of metastatic disease. Some studies have shown a
      recurrence rate of 40% or more at 10 years in this relatively good prognostic
      group. The incidence of breast cancer continues to increase approximately 1% per
      year with a great increase in the frequency of early stage disease (particularly
      in situ carcinoma). The increased use of mammography and physical examination
      with appropriate follow-up will increase the frequency of diagnosis of node
      negative patients compared with those with more advanced stages. Women with
      positive axillary nodes who are premenopausal benefit from adjuvant chemotherapy,
      whereas those who are postmenopausal have shown a clear reduction in mortality
      when treated with tamoxifen. It is even more reasonable to speculate that women
      with node-negative disease could have an even greater benefit from adjuvant
      therapy because they have a lower tumor burden at the time of diagnosis. Compared
      with earlier clinical adjuvant trials, more recent studies (1981-89) have shown a
      disease-free survival advantage for node-negative breast cancer patients treated
      with adjuvant chemotherapy. Hopefully, the differences noticed in disease-free
      survival will show a similar survival advantage with further observations. The
      results of these clinical trials suggest that adjuvant chemotherapy may be of
      benefit to patients with node-negative disease but do not support the contention
      that all node-negative patients with breast cancer should receive adjuvant
      chemotherapy. Some prognostic subgroups (tumor size greater than 2 cm) have shown
      an overall 10-year survival rate of 92% for women who have not received adjuvant
      therapy. The benefits versus toxicities of adjuvant therapy should be carefully
      evaluated before the initiation of adjuvant therapy.

PMID- 2001571
TI  - Physician tax credit or deduction. A different concept to improve access and
      monitoring of indigent patients for cancer surveillance and monitoring.

PMID- 2001572
TI  - Access to high-tech health care. Ethics.
AB  - Access to health care has always been limited by personal and social economics.
      Poverty remains one element that correlates with poor prognosis in all varieties
      of cancer. Prior to becoming standard therapy, elements of high-tech health care
      are often widely available as research protocols, participation in which is
      generally available without considerations of insurance coverage or personal
      wealth. Any person may still volunteer participation in research protocols and
      thereby partake in high-tech advances even before these become standard therapy.
      However, recent developments in the conduct of research now may limit
      participation. Medicare and third party insurance payers proscribe payment for
      research project care and always have. Recently, more than ever before,
      reimbursements to physicians and health care institutions have been more closely
      scrutinized to reject all payment in research settings. In situations in which
      cost and availability of the new technology, whether machine or drug, limit
      participation, research entrepreneurs have made research participation available
      to only those who can pay for it. These and similar developments threaten to
      limit access to high-tech health care and to actually impede cancer research.

PMID- 2001573
TI  - Measuring the quality of care for the cancer patient.
AB  - In recent years, the efforts to better define quality of patient care have
      focused on attempts to improve on the measurement of quality. These efforts raise
      three questions: (1) Why attempt to measure quality? (2) What is the best way to
      measure quality of care of the cancer patient? and (3) What must be done to
      achieve this? Three main reasons for measuring quality of patient care are to
      describe the current state, plan strategies for improvement, and implement and
      monitor improvements. To measure quality, both the definition of quality and the
      tools available for measurement must be addressed. The difficulty in developing a
      measurable definition of quality is achieving agreement on the measurable
      components of quality. The tools to measure quality have evolved to focus on
      monitoring of key indicators for comparative use. The utility of indicators lies
      in demonstrating that they have the capacity to identify opportunities for
      improving care. The Joint Commission is improving measurement tools through the
      development and testing of oncology indicators for reliability and the capacity
      to identify opportunities for improving care. The development and teaching of new
      quality improvement methods to health care professionals also is necessary.

PMID- 2001574
TI  - Continuity of cancer care.
AB  - The importance of providing continuity in the care of all patients with major
      medical problems, such as cancer, has widespread acceptance in our current health
      care system. From the perspective of an oncology social work clinician, this
      article offers a definition of the concept of continuity of care, examines
      factors influencing its provision in oncology, and reviews key components in
      continuity of cancer care planning and implementation. It also examines some
      innovative efforts in practice to improve continuity.

PMID- 2001575
TI  - A provider's view of prevention approaches in a prepaid group practice.
AB  - Kaiser Permanente's health care delivery system and its efforts to integrate
      public health preventive medicine and curative medicine are described. The author
      advocates an increased focus on prepaid delivery systems like Kaiser Permanente
      as the best vehicle to achieve the full promise of health screening, health
      education, and life-style modification. Because these systems have brought the
      proper incentives into alignment, prevention and health promotion have become
      effective tools to achieve cost containment goals. A number of Kaiser Permanente
      projects are highlighted that demonstrate integration of public health preventive
      medicine and curative medicine: the Northern California Region's uniform health
      appraisal examination, which is linked with health education and counseling; the
      Colorado Region's breast cancer screening program, which is expected to show a
      higher rate of early breast cancer detection than in the general population;
      cooperative efforts with two Northern California towns to reduce smoking through
      a community-wide project; educational theatre programs aimed at early
      intervention and education of children before high-risk behaviors have become
      established life-style; and research projects that are possible because of an
      integrated program. Also, several forces that could endanger integrated systems
      including cost control practices of employers and insurers, and public policy
      such as mandating specific benefits, are noted.

PMID- 2001576
TI  - Changing demographics in the United States. Implications for health
      professionals.
AB  - The coming decade will bring dramatic changes in the composition of the American
      population. Changes in immigration laws, illegal and legal immigration into this
      country, and the aging of the "baby boomers" will all result in profound changes
      in the demographics of this country. These demographic changes will necessitate
      alterations in all aspects of the health care system. This article focuses on the
      projected changes that will occur in relation to the elderly, Hispanics, Asian
      Americans, and the economically disadvantaged, and on the related implications
      for health care professionals. The cancer incidence and mortality rates for each
      discussed minority group differ from the rates presently reported for white
      Americans. Thus, health professionals will have to be aware of the differences
      among these groups and tailor their primary and secondary prevention efforts
      accordingly. The future task for all health care providers serving minorities and
      the elderly will be to familiarize themselves with the special health problems of
      the population with whom they work and with the ethnocultural barriers that deter
      proper use and delivery of health services.

PMID- 2001577
TI  - Clinical trials. Access and reimbursement.
AB  - Clinical trials continue to play an extremely important role in clinical
      oncology, but of the nearly 1 million cancer patients diagnosed in the United
      States each year, only 2.5% (25,000) participate in such trials. Access to
      clinical trials has been enhanced by the adoption by the NCI of a promotional
      campaign that involves seminars, dissemination of information to national and
      local news media, and assisting in making information about clinical trials
      available to patients and physicians. Factors that hinder accrual of patients to
      clinical trials include: (1) physicians' concern about losing contact with
      patients, (2) physicians who feel that "experimental therapy" is not as good as
      "standard therapy," and (3) the time it takes to discuss and implement clinical
      trials. Reimbursement for clinical trials has also become a major concern. Who
      should pay for clinical research? Many insurance companies have been reluctant to
      pay for "experimental therapy" but will pay for "standard therapy." If this trend
      continues, the whole concept and organization of clinical trials, i.e., Phase I,
      II, and III trials, will be greatly hindered. Solutions must be found, and third
      party payers need to realize that an investment in clinical trials today will
      decrease the long term costs of state-of-the-art care.

PMID- 2001578
TI  - Patient perceptions.
AB  - The cancer patient's perceptions about treatment, prognosis, and long-term care
      have emerged in the context of interaction with the changing healthcare system. A
      brief overview of cancer patients' perceptions regarding their disease and
      subsequent care is provided. The economic, organizational, and technological
      environment in which this care is provided and the patient's perceptions of that
      environment are discussed. In addition to economic pressures, the ever-increasing
      number of cancer patients, prolonged survival, and patients' perceptions have
      created changes in the healthcare system. These changes are mediated by important
      socioeconomic, cultural, and demographic characteristics of the cancer patient.
      Recommendations to address these changes are discussed.

PMID- 2001579
TI  - Alternative therapies, 1990. An overview.
AB  - The availability of alternative therapies for many health problems is a well
      documented historical fact. Alternative therapies are generally understood to be
      those therapies outside of the usually accepted medical therapies for disease
      processes, such as cancer, arthritis, diabetes, psoriasis, lupus, and AIDS. Some
      other descriptive terms utilized include questionable, unproven, dubious,
      unorthodox, and unconventional. These alternative therapies vary from active
      involvement in promotion of one's own health (exercise, diet) to quackery. In
      today's society, with emphasis on self-involvement with individual health,
      metabolic therapies have become the most widely practiced alternative therapy. In
      an antiestablishment, anti-intellectual climate, with an increasingly mobile,
      rootless population, alternative therapies are in somewhat of a renaissance. Some
      confusion exists regarding clinical trials and alternative therapies in the
      general population and in the noninvolved health profession. Various studies
      indicate that from 10% to 50% of cancer patients use some alternative therapy,
      with national expenditures ranging as high as $10 billion annually. Better
      educated patients with higher-than-average income are more likely to choose
      alternative therapies and are frequently supported by a physician in this choice.
      Most cancer patients continue under a physician's care and continue usual therapy
      while pursuing alternative methods. Approximately 5% of cancer patients abandon
      appropriate therapy and pursue potentially harmful alternative methods. A variety
      of sociomedical questions are brought forth by studies of the use of alternative
      therapies. A great need for public and professional education regarding this
      subject is evident.

PMID- 2001580
TI  - Facilitating clinical trials. The expanding role of the nurse.
AB  - Clinical trials are becoming increasingly difficult to carry out in the face of a
      changing health care delivery system. The reluctance of third party payers to
      reimburse for experimental therapy and the growing practice of providers to limit
      resources allocated for the care of cancer patients undergoing such therapies
      seriously curtail the ability of investigators to test new cancer treatments
      clinically. In addition, certain beliefs, attitudes, and perceptions held by the
      public may interfere with patient case accrual. Nurses can help facilitate both
      accrual to and conduct of clinical research. This article addresses selected
      consumer- and provider-centered factors that inhibit clinical research. The
      expanding role of the nurse in the areas of public education, informed consent,
      direct care, and collaborative research is also described.

PMID- 2001581
TI  - Clinical trials. A family physician's perspective.
AB  - Primary care specialists diagnose and manage a wide variety of problems. Cancer
      is one relatively small part of the practice of these clinicians. Patients with
      newly diagnosed cancer usually are referred to surgical specialists. Primary care
      physicians often determine future events after surgical care. Oncologists may or
      may not be consulted depending on tumor type and past experiences of the
      physician, patient, and patient's family. Many primary care physicians think that
      chemotherapy regimens given empirically have little if any scientific evidence to
      support their use. Side effects of cancer treatment regimens often cause
      suffering and profoundly effect quality of life. There is a lack of communication
      between oncologists and primary care physicians. Dialogue between oncologists and
      primary care doctors may help solve communication problems. Clinical trials help
      determine which treatments are effective. Many clinical trials are conducted at
      the community hospital level. Most primary care physicians support clinical
      trials once they know about them. Education activities should be directed at
      promoting patient referral for participation in clinical trials.

PMID- 2001582
TI  - An inner city cancer prevention clinic. Design, methods, and early results.
AB  - An American Cancer Society demonstration pilot project is underway that is
      designed to provide comprehensive cancer prevention-related services to the
      underserved community of West Oakland, California. An array of cancer prevention
      services are being made available through an inner-city clinic (West Oakland
      Health Center), including cancer risk assessments and education about cancer,
      physical examinations for cancer, teaching of self-examination procedures,
      smoking cessation, and nutrition counseling, appointments for Pap smears,
      sigmoidoscopy, mammography, and other more specialized screening procedures, case
      management for findings suspicious for cancer, and community education programs.
      Described is the process of implementing these services, their utilization, and
      their impact (after 6 months).

PMID- 2001583
TI  - Increasing the cancer screening of the medically underserved in south Florida.
AB  - Diagnosis and treatment of cancers at advanced stages have contributed to a
      significantly lower survival rate among individuals of low socioeconomic status
      compared with those in higher brackets. In an effort to increase the
      accessibility and acceptability of cancer screening among such individuals in
      Dade County, Florida, the Cancer Control Division of the Sylvester Comprehensive
      Cancer Center at the University of Miami School of Medicine initiated a pilot
      early detection program in 1987. The program initially provided breast cancer
      screening for women, aged 40 and older, who attended ten community health care
      centers located in low-income neighborhoods. With the selection of Miami by the
      American Cancer Society as one of three sites for conducting a screening
      demonstration project for the socioeconomically disadvantaged, this program has
      recently been expanded to include pelvic screening for women, aged 40 and older,
      and prostate screening for men, aged 65 and older.

PMID- 2001584
TI  - Prevention and changing demographics. The underserved and cancer.
AB  - This paper illustrates the complexity of the "cancer control in the underserved"
      problem, especially as it is affected currently, and will be in the future, by
      the multiple demographic changes in the United States. It does so by extensively
      quoting from four rather different articles by authors from a variety of
      backgrounds in health, management, and economics. Another issue is that although
      the articles quoted refer mainly to secondary and tertiary prevention, they do
      apply equally to primary prevention and health promotion. Furthermore, the twin
      issues of priority and ethnic/cultural differences need to be addressed insofar
      as they affect health risks, risk reduction efforts, early diagnosis, treatment,
      and rehabilitation/disability reduction. Finally, the point is made that social
      and structural change of this magnitude cannot occur in the health care system
      and society at large without the allocation of discrete private and public sector
      resources.

PMID- 2001585
TI  - Primary prevention of cancer. The case for comprehensive school health education.
AB  - Comprehensive school health education plays an important role in the primary
      prevention of cancer because so many of the health habits relating to cancer and
      other diseases have their onset early in life. A comprehensive health education
      program should begin early in life. Such education must be multifactorial from
      kindergarten through high school, should involve annual health screening, must be
      assessed annually, and is most effective when coordinated by a full-time health
      education teacher. Those concerned about the many problems of health behavior in
      our society should insist that such programs become mandatory in every state in
      this nation.

PMID- 2001586
TI  - Proteoglycans as modulators of growth factor activities.

PMID- 2001587
TI  - Similarities between the homeodomain and the Hin recombinase DNA-binding domain.

PMID- 2001588
TI  - Structural relationship between an iron-regulated RNA-binding protein (IRE-BP)
      and aconitase: functional implications.

PMID- 2001589
TI  - Distributive segregation: motors in the polar wind?

PMID- 2001590
TI  - Identification and purification of a protein that binds the yeast ARS consensus
      sequence.
AB  - We have identified a yeast protein that binds specifically to the ARS consensus
      sequence. By two-step chromatography we have purified the factor to apparent
      homogeneity as a single polypeptide of 67 kd. The purified ARS consensus-binding
      protein (ACBP) recognizes the ARS consensus of the four genomic ARS elements
      tested, binding preferentially to the T-rich single strand. Point mutations in
      the consensus significantly reduce the affinity of the single-strand binding. At
      the histone H4 ARS, ACBP recognizes both the perfect ARS consensus and a 9/11
      match 3' of it. These two binding sites correlate with the boundaries of the
      minimal functional H4 ARS element. A similar configuration of binding sites is
      found at ARS1. We propose a model implicating this factor in an early step of the
      initiation of DNA replication.

PMID- 2001591
TI  - DNA binding and I kappa B inhibition of the cloned p65 subunit of NF-kappa B, a
      rel-related polypeptide.
AB  - The sequence and biochemical properties of the product of the cloned cDNA for the
      p65 subunit of nuclear factor kappa B (NF-kappa B) have been determined. The cDNA
      has an open reading frame of 549 amino acids capable of encoding a 60 kd protein.
      NF-kappa B p65 contains an amino-terminal region of 320 amino acids with
      extensive similarity to the oncogene c-rel and lesser similarity to NF-kappa B
      p50. In vitro translated p65 forms a DNA-binding complex with NF-kappa B p50, and
      the binding of this complex can be specifically inhibited by purified I kappa B.
      Progressive carboxy-terminal deletions of p65 show that, contrary to previous
      assumptions, p65 does include a DNA-binding domain that in vivo might become
      activated only through hetero-oligomerization with p50. DNA binding by truncated
      p65 is inhibited by I kappa B, thus mapping the I kappa B interaction domain to
      the rel-homologous region and suggesting that I kappa B exerts its inhibitory
      effect upon NF-kappa B primarily through interaction with p65.

PMID- 2001592
TI  - Mechanism of action of an acidic transcriptional activator in vitro.
AB  - Transcription of a eukaryotic structural gene by RNA polymerase II requires the
      ordered assembly of general transcription factors on the promoter to form a pre
      initiation complex. Here we analyze affinity-purified complexes at various stages
      of assembly to determine the mechanism of action of an acidic transcriptional
      activator. We show that the activator can function in the absence of ATP and
      stimulates transcription by increasing the number of functional preinitiation
      complexes. The activator effects this increase by recruiting the general
      transcription factor TFIIB to the promoter. Using protein affinity chromatography
      we demonstrate a specific interaction between an acidic activating region and
      TFIIB. Based on these combined results, we propose that TFIIB is a direct target
      of an acidic activator.

PMID- 2001594
TI  - AIDS in women--United States.

PMID- 2001593
TI  - AIDS surveillance in Canada.

PMID- 2001595
TI  - Mycobacterium shimoidei: first reported isolate in Canada.

PMID- 2001596
TI  - Cluster of cases of Creutzfeldt-Jakob disease--Ontario.

PMID- 2001597
TI  - [Nursing care of double island skin tube from perineum and scrotum one stage
      urethroplasty].

PMID- 2001598
TI  - [Control of delivery time--analysis of 2391 cases].

PMID- 2001599
TI  - [Nursing care of implanting silica gel artificial eyeball with self-sclera
      reinforcing].

PMID- 2001600
TI  - [Iontophoresis of fluoride for caries prevention].

PMID- 2001601
TI  - [Quality control of perioperative care].

PMID- 2001602
TI  - [Blood-gas analysis for resuscitation of heart and lung patients].

PMID- 2001603
TI  - Accumulation of hyporesponsive, calcium extruding memory T cells as a key feature
      of age-dependent immune dysfunction.
AB  - In this review I propose a hypothesis with a number of testable predictions: that
      the age-dependent decline in T lymphocyte function is largely the result of the
      accumulation of memory T lymphocytes with over-active plasma membrane calcium
      pumps. This idea is consistent with much, though not all, of the currently
      available data. I will start by presenting the evidence that suggested and most
      clearly supports this idea, then discuss apparently contrary data (some of it
      still difficult to reconcile with the model), and lastly consider the
      implications of the model for our understanding of late life development of the T
      cell immune system.

PMID- 2001604
TI  - Autoantibodies in D-penicillamine-induced myasthenia gravis: a comparison with
      idiopathic myasthenia and rheumatoid arthritis.
AB  - The distribution of autoantibodies was studied in patients with rheumatoid
      arthritis (RA) treated by D-penicillamine and who developed myasthenia gravis
      (MG). The anti-human acetylcholine receptor (AChR) antibodies were specifically
      associated with clinical symptoms of MG without any difference in the pattern of
      specificities in idiopathic (id-MG) or in induced MG (DPen-MG). Conversely, anti
      nuclear antibodies were elevated in DPen-MG sera compared to id-MG sera (P less
      than 0.001) but were also compared to patients with RA treated by D-penicillamine
      (or thiopronine) and who did not develop MG. Anti-denatured DNA antibodies were
      enhanced in sera from treated patients, whether they had presented or not a MG
      disease. Anti-histone antibodies were associated with RA. These observations
      suggest that the immunological imbalance in RA patients, can be increased by a
      drug treatment which may trigger the appearance of a second autoimmune disease
      such as MG, where anti-AChR antibodies are associated with anti-nuclear
      antibodies.

PMID- 2001605
TI  - Enhancement of in vitro lipopolysaccharide-stimulated interleukin-1 production by
      levamisole.
AB  - The production of interleukin-1 (IL-1) by the P388D1 mouse macrophage cell line
      and by adherent peritoneal exudate cells (PMs) was examined. In vitro IL-1
      production by P388D1 cells treated with lipopolysaccharide (LPS) was enhanced by
      coculture with levamisole (0.1 to 10 microM). Oral administration of levamisole
      (3 mg/kg) to mice also resulted in potentiation of in vitro IL-1 production by
      thioglycollate-elicited peritoneal macrophages in response to in vitro LPS
      stimulation. Potentiation was approximately twofold. IL-1 production in the
      absence of LPS by either the P388D1 cells or the PMs was nil, and levamisole did
      not directly stimulate IL-1 production in these cases. IL-1 activity in the
      culture supernatants was measured by thymocyte comitogenic assays. The
      immunochemical identify of the thymocyte comitogenic activity as IL-1 alpha was
      confirmed by neutralization with a specific goat anti-mouse IL-1 alpha antiserum.
      These results suggest that one mechanism by which levamisole acts to normalize
      and restore immune responses may be enhancing the signals which enable activated
      macrophages to secrete IL-1.

PMID- 2001606
TI  - Idiopathic intracranial hypertension.

PMID- 2001607
TI  - Therapy of acute and chronic multiple sclerosis.

PMID- 2001608
TI  - Therapeutic options in acute diverticulitis.
AB  - Diverticulitis is a serious intra-abdominal infection that ultimately afflicts
      about one in four patients having colonic diverticulosis. The illness may be
      indolent or fulminant, depending on the degree of colonic spillage and its
      containment. Most patients require hospitalization, and medical therapy suffices
      in about three fourths. Those who fail aggressive medical management and those
      with recurrent acute attacks, diffuse peritonitis, abscess, persistent
      obstruction, or fistulization require surgical intervention. Abdominal CT
      scanning has supplanted the contrast enema as the acute diagnostic procedure of
      choice and allows guided percutaneous drainage of large abscesses in selected
      cases. This approach helps realize the surgical ideal of a single elective
      operation without a temporary colostomy. For those patients still requiring
      emergency surgery, the two-stage approach employing resection of the diseased
      colon at the initial operation is far superior to the older three-stage approach.

PMID- 2001609
TI  - Colorectal cancer--diagnosis, management, and prognosis.

PMID- 2001610
TI  - Patient-controlled analgesia: a new method for pain control.

PMID- 2001611
TI  - Update on trace elements.

PMID- 2001612
TI  - The role of interleukin-2 in cancer immunotherapy.
AB  - The arena of cellular immunotherapy is an emerging field of study. The field has
      strong foundations in numerous animal tumor models, which provide avenues of
      research for refinements in human immunotherapy. Experience from a number of
      research centers can be generalized: LAK cell trials in humans have demonstrated
      that PBMCs activated with IL-2 possess reproducible antitumor activity in vitro.
      Exogenous IL-2 administration to patients is required to maintain the biologic
      activity of the activated cells, although the requirement for LAK cells in tumors
      like melanoma is not clear-cut. Overall, the response rate to immunotherapy in
      humans is approximately 30%. The toxicity of immunotherapy, which is related to
      the dose of systemic IL-2, can be significantly reduced. The next generation of
      trials of cellular immunotherapy in humans will use TILs. Murine experiments
      indicate that this population of cells is more powerful and potentially more
      specific for tumor than LAK cells. Like LAK cells, TILs also require exogenous IL
      2 for optimum performance in vivo. The difficulty in reproducible TIL growth can
      be overcome by the use of monoclonal antibody activation and IL-2. Improvements
      in TIL therapy are anticipated from the use of TILs combined with hybrid
      antibodies, the addition of other biologic response modifiers, and the
      implementation of genetically engineered cells and cell products.

PMID- 2001613
TI  - Ventricular ectopy: significance and management.
AB  - Ventricular ectopy is a normal variant of cardiac rhythm, and its significance in
      an individual is related to cardiac risk factors and the presence or absence of
      heart disease. Although there is good evidence in many forms of heart disease
      that complex VEBs indicate a high risk of death, treatment of asymptomatic VEBs
      with antiarrhythmic drugs has not been shown to improve survival and may be
      hazardous. Treatment should be directed at the underlying heart disease. Those
      with heart disease and severe symptoms resulting from VEBs will often require
      electrophysiological assessment as to specific antiarrhythmic therapy. Those
      without heart disease can usually be managed by reassurance and do not require
      antiarrhythmic drugs.

PMID- 2001614
TI  - Stochastic interactive processes and the effect of context on perception.
AB  - The effects of context on perceptual identification responses given without time
      pressure are well-described by classical models in which contextual and stimulus
      information exert independent effects. A recent article by Massaro (1989) raises
      the possibility that interactive models, such as the TRACE model of speech
      perception, are inherently incompatible with these classical context effects. The
      present article shows that this incompatibility hypothesis can be rejected.
      Mathematical analysis and computer simulation methods are used to show that
      interactive models can exhibit the classical effects of context, if there is
      variability in the input to the network or if there is intrinsic variability in
      the network itself. A variety of interactive models which incorporate variability
      can all produce the classical context effects, at least under some conditions;
      the conditions are rather general in the case of one of the variants. The
      findings suggest that interactive models should not be viewed as alternatives to
      classical accounts, but as hypotheses about the dynamics of information
      processing that lead to the global asymptotic behavior that the classical models
      describe.

PMID- 2001615
TI  - Broken agreement.
AB  - The subjects and verbs of English sentences agree in number. This superficially
      simple syntactic operation is regularly implemented by speakers, but occasionally
      derails in sentences such as The cost of the improvements have not yet been
      estimated. We examined whether the incidence of such errors was related to the
      presence of subject-like semantic features in the immediate preverbal nouns, in
      light of current questions about the semantic versus syntactic nature of sentence
      subjects and the interactivity of language processing. In three experiments,
      speakers completed sentence fragments designed to elicit erroneous agreement. We
      varied the number and animacy of the head noun and the immediate preverbal
      (local) noun, as well as the amount of material separating the head noun from the
      verb. The plurality of the local noun phrase had a large and reliable effect on
      the incidence of agreement errors, but neither its animacy nor its length
      affected their occurrence. The latter findings suggest, respectively, that the
      semantic features of sentence subjects are of minimal relevance to the syntactic
      and morphological processes that implement agreement, and that agreement features
      are specified at a point in processing where the eventual length of sentential
      constituents has little effect on syntactic planning. Both results follow
      naturally from explanations of language production that emphasize the segregation
      of sentence formulation processes into relatively autonomous components.

PMID- 2001616
TI  - Some ideas for a new year.

PMID- 2001617
TI  - The measurement of craving in cocaine patients using the Minnesota Cocaine
      Craving Scale.
AB  - Drug craving is an irresistible urge that compels drug-seeking behavior, and
      which often accounts for relapse among treated cocaine users. A cocaine craving
      scale that has proven reliable and practical in clinical treatment research with
      cocaine-using subjects is presented. It assesses intensity, frequency, and
      duration of this entirely subjective phenomenon. Data from 234 scales completed
      by 35 patients in treatment showed that craving for cocaine was of variable
      intensity, experienced relatively few times per day (zero to two), and of short
      duration (less than 20 minutes). Internal consistency among the three scales was
      robust, shown by a standardized item alpha of .826. The use of this scale should
      allow for each component of craving to be studied separately.

PMID- 2001618
TI  - Stability of psychopathology dimensions in chronic schizophrenia: response to
      clozapine treatment.
AB  - Current models of schizophrenia postulate that different symptom complexes,
      including the positive and negative, may relate to fundamental underlying
      neurobiological distinctions. However, the premise of an underlying stability to
      the psychopathological profile has not been systematically investigated,
      particularly in response to pharmacological intervention. The present work aimed
      to study this issue in 14 chronic schizophrenic inpatients by comparing their
      symptom clusters before and after a 20-week course of clozapine treatment. The
      results indicated significant improvement on all eight symptom dimensions, as
      well as in severity of general psychopathology. Despite the clinical gains, most
      dimensions remained highly stable, with correlations between prestudy and
      clozapine week 20 ranging up to .91 (P less than .0001) for the positive-negative
      composite score. These findings of stability over time, even in response to
      potent treatment, support the validity and importance of schizophrenic
      psychopathology dimensions, which appeared to possess fundamental traitlike
      characteristics.

PMID- 2001619
TI  - Psychopathology in drug abusers and their families.
AB  - Demographic, clinical, and family pedigree data obtained on 350 hospitalized drug
      dependent patients showed that 52% also met DSM-III criteria for alcohol abuse or
      dependence, while 37% met DSM-III criteria for a concurrent axis I psychiatric
      disorder other than substance abuse. Cyclothymic disorder was significantly more
      common among cocaine abusers, while generalized anxiety disorder and panic
      disorder were more common among sedative-hypnotic abusers. Data on 1,478 first
      degree relatives revealed that the prevalence of alcoholism and affective
      disorder was highly correlated with the occurrence of similar psychopathology in
      the probands. These findings suggest a relationship between drug of choice and
      comorbid psychopathology, a role for familial factors in the transmission of
      these disorders, and the importance of diagnostic subtypes in the evaluation and
      treatment of substance abusers.

PMID- 2001620
TI  - Initial stages of validation by penile volume assessment that sexual orientation
      is distributed dimensionally.
AB  - Kinsey concluded that homosexuality and heterosexuality were distributed
      dimensionally in the normal population, a significant percentage of whom
      experienced homosexual feelings. This conclusion has been ignored by most sex
      researchers. Twenty men seeking treatment for compulsive sexual behaviours
      reported a dimensional distribution of heterosexual and homosexual feelings,
      rated by questionnaire on 11-point scales. Their penile volume responses to 10
      second movies of nude women and men were assessed. Significant correlations were
      found between individual subjects' penile volume and questionnaire assessment of
      heterosexual/homosexual feelings, validating their questionnaire-assessed
      dimensional distribution of their feelings. The finding was considered to provide
      the initial stage of physiological validation of the questionnaire, which in
      previous studies demonstrated a dimensional distribution of
      heterosexual/homosexual feelings in representative samples of medical students,
      supporting Kinsey's conclusion.

PMID- 2001621
TI  - The reliability of "bizarre" delusions.
AB  - The concept of bizarre delusions figures prominently in the diagnosis of
      schizophrenia under DSM-III-R criteria. Yet this concept may be difficult to
      apply in the clinical world. The interrater reliability of distinguishing bizarre
      versus non-bizarre delusions was estimated by compiling a sample of 40 delusional
      ideas and asking a group of psychiatrists (ranging from experts in the field to
      residents) to identify them as bizarre or non-bizarre. The interrater reliability
      of the 45 respondents was consistently low as measured by kappa statistic (kappa
      less than 0.40) within and across groups of raters, and regardless of whether or
      not a structured definition was applied. Implications for DSM-IV are discussed.

PMID- 2001622
TI  - Can personality traits predict psychotherapy outcome?
AB  - Ninety-six new admissions to a psychiatric outpatient clinic who attended a
      median of 14 therapy sessions completed a self-report Personality Profile Index
      prior to their first session. This index provides scores on eight dimensions of
      personality, a conflict measure, and a measure of social desirability. Scores
      were correlated with number of sessions and outcome as measured by a Symptom
      Checklist and by a Global Assessment Scale (GAS). Improvement was significantly
      related to number of sessions attended. Patients scoring high on being rejecting
      of others (rejection) were significantly less likely to show improvement after
      therapy. Rejection, aggression, passivity, and conflict were significantly
      related to the extent of symptoms and problems with which patients presented at
      the clinic.

PMID- 2001623
TI  - Autism in schizophrenia revisited.
AB  - The concept of autism is reviewed in its historical evolution. It is suggested
      that the Bleulerian insistence on the withdrawal component in autism contributed
      to the decline of its use in adult psychiatry. Phenomenology offers another
      approach to grasping the nature of autism as a relational (subject-outer world)
      phenomenon. European phenomenological psychiatry in the field of schizophrenia is
      introduced and its attempts to reveal the essence of autism are presented. Autism
      is here considered as a "loss of vital contact with reality" (Minkowski),
      "inconsistency of natural experience" (Binswanger), or "the global crisis of
      common sense" (Blankenburg). It is proposed that autism represents dysfunctional
      perceptual/expressive attunement to the outer world. The usefulness of this
      concept is briefly examined in relation to the diagnosis and etiopathogenesis of
      schizophrenia.

PMID- 2001624
TI  - An adoption study of attention deficit/hyperactivity/aggression and their
      relationship to adult antisocial personality.
AB  - This study used an adoption design to investigate the relationships among genetic
      background, environmental factors, and clinical outcome of attention
      deficit/hyperactivity, aggressivity, and adult antisocial personality (ASP) in a
      sample of 283 male adoptees. A biologic parent adjudged to be delinquent or to
      have an adult criminal conviction predicted increased attention
      deficit/hyperactivity in the adopted away sons, as well as increased adult ASP
      diagnosis. Aggressivity in the adoptee was predicted by attention
      deficit/hyperactivity, and aggressivity in turn predicted increased adult ASP.
      Environmental factors of socioeconomic status (SES), and psychiatric problems in
      adoptive family members correlated significantly with various clinical outcomes
      of aggressivity, attention deficit/hyperactivity, and ASP. The results suggest
      that attention deficit/hyperactivity should be considered a syndrome that has a
      variety of correlated behaviors, such as aggressivity, and that each of these
      correlated behaviors is influenced by different genetic and environmental factors
      and their interactions. Depending on the mix of factors, adult ASP can be one of
      the outcomes.

PMID- 2001625
TI  - Major depressive disorder as a prominent but underestimated feature of fragile X
      syndrome.
AB  - Three unrelated institutionalized mentally retarded males with fragile X syndrome
      presented major depressive disorders. Their depressive moods were long
      unrecognized because of the difficulties in assessing depressive symptoms in
      mentally retarded individuals. The genetic implications of establishing the
      diagnosis of this common heritable X-chromosome abnormality and the therapeutic
      consequences of detecting the depression are emphasized. Fragile X [fra(X)] may
      be a genetic predisposition to neuropsychiatric disorders with a variable range
      of manifestations. The fragile X syndrome may be helpful as a biologic model for
      studying the relationship between specific genetic factors and biological forms
      of psychopathology.

PMID- 2001626
TI  - Depressive and negative symptoms in major psychiatric disorders.
AB  - Among 193 inpatients with Research Diagnostic Criteria (RDC) major psychiatric
      disorders, the scores in Hamilton's Rating Scale for Depression (HRSD) were
      higher among those patients with RDC schizoaffective disorder depressed type and
      major depressive disorder, whereas the scores in the Scale for Assessment of
      Negative Symptoms (SANS) were higher among patients with these two disorders, as
      well as those with RDC nonaffective psychoses (schizophrenia and unspecified
      functional psychosis). The HRSD and SANS items were factor-analyzed, yielding
      nine factors that discriminated depressive and negative symptoms. These findings
      suggest that although depressive and negative symptoms frequently coexist, they
      constitute discrete syndromes.

PMID- 2001627
TI  - Autologous bone marrow transplantation.
AB  - Several malignancies have shown a dose-response relationship. The hematopoietic
      toxicity of dose escalations is often rescued by bone marrow transplantation.
      Prolonged disease-free survival can now be expected for patients with lymphoma,
      Hodgkin's disease, leukemia and breast cancer when high-dose cytotoxic therapy
      (high dose CT) is followed by autologous bone marrow transplant (AuBMT). Bone
      marrow (BM) and/or peripheral blood (PB) can be cryopreserved before high-dose CT
      and are utilized for stem cells rescue for AuBMT. Clinical trials of patients
      with lymphoma, leukemia, Hodgkin's disease, and breast cancer have proven the
      importance of timing the induction and high-dose CT, and properly sequenced
      therapy has resulted in prolonged disease-free survival in these patients. The
      rationale for high-dose cytotoxic therapy, methods of stem cells
      cryopreservation, the complications of high-dose CT, and results of treatment for
      various malignancies are briefly detailed with emphasis on designing future
      trials. Carefully designed trials have proven the usefulness of AuBMT and offer a
      promising approach to the future of cancer chemotherapy.

PMID- 2001628
TI  - Congenital miliaria crystallina.
AB  - Miliaria crystallina is characterized by intracorneal or subcorneal, 1 to 2 mm,
      clear, noninflammatory vesicles that typically appear in crops after a severe
      sunburn or during a febrile illness. They frequently occur in neonates, most
      likely due to lack of maturation of the sweat duct during the first few days
      following birth, but are rarely present at delivery. We describe here a patient
      with extensive miliaria crystallina that was present at birth and review possible
      theories of the pathogenesis of these lesions.

PMID- 2001629
TI  - Trichotillomania associated with the "Friar Tuck sign" and nail-biting.
AB  - Trichotillomania is a form of traction alopecia resulting from compulsive
      repetitive removal of one's own hair. This entity can mimic the clinical
      appearance of many other forms of hair loss including alopecia areata,
      androgenetic alopecia, and tinea capitis. It is important to differentiate
      trichotillomania from other forms of alopecia because its treatment is quite
      different. We present three cases of trichotillomania demonstrating the "tonsure
      pattern" or "Friar Tuck sign" and onychophagia (nail-biting), which we describe
      as clinical identifying features of this syndrome.

PMID- 2001630
TI  - Cheyletiella dermatitis: a report of fourteen cases.
AB  - Cheyletiella dermatitis is an infrequently reported eruption caused by an
      ectoparasite whose normal hosts are household pets. Fourteen cases, documented
      over an eight-year period, are reported. All cases were found in one practice in
      a small community. Typical patients are female, aged forty years or younger, who
      experience pruritic papules in the winter months. Cheyletiella dermatitis is not
      a rare problem.

PMID- 2001631
TI  - Tuberculoid leprosy: a case report.
AB  - A case of tuberculoid leprosy, undiagnosed and consequently untreated for four
      years, is presented. This case report is presented in an attempt to alert the
      clinician to the occurrence of leprosy in American population and to raise the
      index of suspicion in the proper clinical setting.

PMID- 2001632
TI  - Positive patch test reactions to nickel, cobalt, and potassium dichromate in a
      series of 576 patients.
AB  - In 1988, 633 patients attending our Allergology Center underwent patch testing
      with the standard series recommended by the Gruppo Italiano Ricerca Dermatiti da
      Contatto e Ambientali. Of these, 576 patients completed the test correctly and
      their results were evaluated statistically. Nickel, cobalt, and potassium
      dichromate were the three most common sensitizers; concomitant positive reactions
      were present at significant levels. The authors discuss environmental and
      occupational exposure to contact allergens and correlate the major sites of
      dermatitis with the sensitivity to each metal in patients of both sexes.

PMID- 2001633
TI  - Breakdown of a chin implant.

PMID- 2001634
TI  - Safety and efficacy of a broad-spectrum sunscreen in patients with discoid or
      subacute cutaneous lupus erythematosus.
AB  - An eight-week, open-label study was conducted to test the efficacy, safety, and
      cosmetic acceptability of a broad-spectrum sunscreen in patients with discoid
      lupus erythematosus or subacute cutaneous lupus erythematosus. The sunscreen
      combined the ultraviolet A absorber avobenzone (Parsol 1789, Givaudan Corp) and
      the ultraviolet B absorber padimate O and had a sun protection factor greater
      than fifteen. The overall clinical disease severity decreased from 2.7 (four
      point scale) at baseline to 1.7 after eight weeks (p = 0.005). Cutaneous signs
      and symptoms, including hyperpigmentation, papules, scaling, and erythema, were
      significantly less severe at the end of the study. The level of protection
      provided by the sunscreen was good to excellent in 54 percent of patients, and
      was judged to be superior or far superior to previously used sun protection
      factor-fifteen sunscreens in 77 percent of patients. Most patients found the
      sunscreen highly acceptable with respect to its cosmetic properties.

PMID- 2001635
TI  - Unusual reactions associated with allergic reactions to nickel.

PMID- 2001636
TI  - Portrait of a practice.

PMID- 2001637
TI  - Perplexing pigmented papules simulating malignant melanoma.
AB  - The clinical presentation of irregularly pigmented papules raises a spectrum of
      diagnostic possibilities. An eighty-five-year-old black man was referred for
      evaluation of lesions of fifty years' duration. The lesions were 1 to 2 cm
      hyperkeratotic, irregularly darkly-pigmented papules limited to sun-exposed
      areas. The histopathologic findings of large keratinocytes, acanthosis,
      hypergranulosis, and orthokeratosis were compatible with a diagnosis of large
      cell acanthoma. We believe large cell acanthoma should be included in the
      differential diagnosis of keratotic or irregularly pigmented lesions on sun
      exposed skin, even in black patients.

PMID- 2001638
TI  - [201Thallium reinjection after exertion-redistribution myocardial scintigraphy. A
      new method for distinguishing between scars and vital myocardium].
AB  - In a prospective study 38 patients (35 men, 3 women; median age 56 [37-71] years)
      with known coronary heart disease in whom conventional thallium-201 exercise
      redistribution myocardial scintigraphy (ERMS) had demonstrated segments with
      diminished activity, thallium-201 was again injected ("reinjection
      scintigraphy"). Its purpose was to test whether in myocardial segments with
      persisting diminished radioactivity improved activity after reinjection provided
      evidence for still viable myocardium. Seven myocardial segments were evaluated in
      each patient, i.e. a total of 266 segments. Activity in the conventional ERMS was
      diminished in 94 of the 166 abnormal segments, but improved on reinjection in 21
      of the 94 segments (22.3%). Nine of the 38 patients (23.7%) benefitted from the
      reinjection: only scar tissue without any viable myocardium would have been
      diagnosed by conventional ERMS in four patients, while extent and spread of
      ischaemic myocardium was better visualized in five.

PMID- 2001639
TI  - [Acupuncture to alleviate pain during colonoscopy].
AB  - 36 patients (18 males and 18 females, mean age 51 [21-76] years) were prepared
      for colonoscopy with acupuncture (points: Hegu, Neiguan, Zusanli and Gongsun
      bilaterally), without acupuncture or pretend acupuncture at points not expected
      to bring about pain relief. In the 12 acupuncture patients mean pain sensitivity,
      estimated during the examination by means of a visual analog scale, was
      significantly (P = 0.003) lower (1.4 +/- 0.4) than in the groups without
      acupuncture (n = 12; 2.7 +/- 0.3) or pretend acupuncture (n = 12; 3.0 +/- 0.3).
      In addition, analgesics and sedatives needed to be given significantly less to
      those with acupuncture (one patient each; P = 0.005) than those without
      (analgesics to five, sedatives to eight patients) or with pretend acupuncture
      (analgesics to four, sedatives to five patients). These data demonstrate that
      pain connected with colonoscopy can be reduced by preceding acupuncture.

PMID- 2001640
TI  - [Eosinophilic gastroenteritis as an allergic reaction to a trimethoprim
      sulfonamide preparation].
AB  - One week after treatment of a urinary infection with co-trimoxazole (twice daily
      160 mg trimethoprim and 800 mg sulphamethoxazole) a 21-year-old man suddenly
      started to vomit, accompanied by watery diarrhoea, abdominal swelling and weight
      loss of 5 kg. Plain X-ray film of the abdomen while standing showed multiple
      fluid levels in the small intestine of the upper and lower abdomen. Serum IgE
      concentration was elevated to 325 U/ml. There was a leukocytosis of
      25,800/microliters, with a differential count of 45% eosinophils. Protein-rich
      ascites contained numerous eosinophils and the mucosa of the terminal ileus and
      the duodenum was infiltrated with eosinophils, findings which indicated
      eosinophilic gastroenteritis. All symptoms regressed completely within 10 days of
      stopping co-trimoxazole and administering prednisolone (50 mg/day). Four years
      later a similar episode of eosinophilic gastroenteritis developed after the
      patient had taken trimethoprim with a sulphonamide (once daily 180 mg
      trimethoprim and 820 mg sulphadiazine). It again quickly responded to short-term
      administration of glucocorticoids.

PMID- 2001642
TI  - [The therapy of chologenic diarrhea].

PMID- 2001641
TI  - [Compartment syndrome after impact trauma from a car bumper].
AB  - A 67-year-old woman, having been hit in the lower leg by a car bumper in a road
      accident, developed a compartment syndrome in the lower leg without any bone
      injury. In the following weeks typical contractures of the affected muscles
      occurred with talipes equinus and clawfoot deformities. In addition there
      developed insertion tendinitis of the affected muscle groups of the anterior
      tibia. A year later magnetic resonance imaging (with normal radiological
      findings) revealed fatty degeneration and muscle fibrosis. The patient complained
      of pain at rest and on movement in the proximal tibia, and there was definite
      pain on pressure over the proximal end of the tibia. Conservative treatment
      having failed, the Achilles tendon and the long flexor muscle of the toes were
      lengthened by operation. Both signs and symptoms then improved. A compartment
      syndrome may develop after blunt trauma even in the absence of bony injury. If
      there are the appropriate clinical signs, intracompartmental pressure measurement
      is the procedure of choice to confirm the diagnosis quickly and thus avoid
      sequelae.

PMID- 2001643
TI  - [Protection against competition for the operators of large technical medical
      equipment during the installation of new equipment in the catchment area. The
      judgement of the Federal Social Court of 9 May 1990].

PMID- 2001644
TI  - [The admissions responsibility of the legal costs insurance in law suits over the
      billing rights of physicians in chief].

PMID- 2001645
TI  - [The therapy of hyperlipidemia in children and young people].

PMID- 2001646
TI  - [Acute segmental hemorrhagic penicillin-associated colitis].

PMID- 2001647
TI  - [Eosinophilic fasciitis].

PMID- 2001648
TI  - [Hyponatremia].

PMID- 2001649
TI  - [Maintenance of remission in acute myeloid leukemia by allogeneic or autologous
      bone marrow transplantation].
AB  - Over a 10-year period 120 patients (58 women, 62 men; median age 33 [14-53]
      years) with acute myeloid leukaemia were treated by allogenic (n = 90) or
      autologous bone marrow transplantation to maintain remission. After a median
      observation time of 41 (11-126) months 64 patients (53%) remain alive without
      recurrence of leukaemia. Ten years after allogenic transplantation performed
      during the first complete remission the probability of disease-free survival is
      50 +/- 8%, as compared with 50 +/- 9% at 4.5 years after autologous
      transplantation. Significant factors influencing disease-free survival after
      allogenic transplantation during the first complete remission were the time
      interval up to the onset of remission and the length of the remission before
      transplantation. The chance of disease-free survival after allogenic
      transplantation in the second complete remission does not so far differ from the
      results achieved by transplantation in the first complete remission. The risk of
      recurrence after autologous transplantation in the first complete remission (47
      +/- 10%) is significantly higher than that following allogenic transplantation
      (18 +/- 10%, P less than 0.0001). Acute graft versus host reactions occurred in
      16% and chronic reactions in 36% of patients after allogenic transplantation. The
      mortality was 38% after allogenic transplantation and 7% after autologous
      transplantation.

PMID- 2001650
TI  - [Coronary angiography with a 5F catheter after percutaneous puncture of the right
      brachial artery. Technique and experience in 70 patients].
AB  - Out of a total of 1640 consecutive left heart catheterizations, 70 (58 males and
      12 females; mean age 56 +/- 8 years) were performed via the right brachial
      artery, in most instances because of occlusive disease of the arteries in the
      pelvic region. 5F catheters were then successfully used for both the coronary and
      left-ventricular angiographies. Noninvasive examinations after two days (Doppler
      ultrasound, oscillography at rest and on exercise, acral plethysmography and
      colour-coded duplex sonography) revealed small haematomas in the region of the
      arterial puncture in four and a haemodynamically insignificant fistula between
      brachial artery and vein in one patient but no aneurysm, stenosis or thrombosis
      at the puncture site. This procedure is thus a valuable addition to invasive
      cardiological diagnosis.

PMID- 2001651
TI  - [Association of arteriovenous and cavernous angioma of the head and neck area].
AB  - A 20-year-old man complained of pulse-synchronous noise in the ear and recurrent
      bleedings in the nose and throat region. From birth he had had an extensive
      haemangioma, black-blue with dark-red parts. It had been diagnosed as a cavernous
      haemangioma, part of a Sturge-Weber syndrome. An angiogram was performed before
      intended dermatological treatment of the disfiguring venous angioma. It
      demonstrated the capillary venous angioma (slow-flow angioma) in the lateral
      triangle of the neck, extending up to the skull base. In addition there was an
      arteriovenous angioma (high flow angioma) in the region of the clivus, which was
      supplied bilaterally largely by the ascending pharyngeal artery. The
      arteriovenous angioma also had connections to the outflow area of the capillary
      venous angioma. These findings and absence of ocular changes excluded Sturge
      Weber syndrome. Because of the risk of life-threatening bleedings, the
      arteriovenous malformation was superselectively embolized by multiple injections
      of nonresorbable polyvinyl-alcohol particles via a microcatheter. This brought
      about the collapse of the cutaneous angiomatous spaces. This case demonstrates
      that external appearance indicating a capillary venous angioma is not reliable.
      Before treatment of this malformation a neuroradiological diagnosis should be
      undertaken.

PMID- 2001652
TI  - [Radioiodine treatment of hyperthyroid states].

PMID- 2001653
TI  - [Exceeding of GOA-determined threshold rates in ambulatory surgery with following
      night duty. Decision of the Luneburg Oberverwaltungsgericht on 5/9/1990].

PMID- 2001654
TI  - [Silicon-induced collagenoses].

PMID- 2001655
TI  - [Early summer meningoencephalitis vaccination and cerebral convulsion attacks].

PMID- 2001656
TI  - [Asymptomatic primary hyperparathyroidism].

PMID- 2001657
TI  - [Cage and domestic birds as excreters of Cryptococcus neoformans].

PMID- 2001658
TI  - [Beta-lactamase production by Haemophilus influenzae].

PMID- 2001659
TI  - [Regression of coronary sclerosis].

PMID- 2001660
TI  - Evaluation of behavioral and cognitive changes: the mental status examination.
AB  - Patients who present to the Emergency Department with a behavioral or cognitive
      disorder should be treated in an organized fashion. The most important element of
      their care is determining the etiology of their abnormality, whether organic or
      functional. The history and physical examination, along with laboratory and
      ancillary testing, should be directed toward this objective. The mental status
      examination plays a critical role in establishing the diagnosis. It must be
      focused and brief. By focusing on seven major areas (affect, attention, language,
      orientation, memory, visual-spatial ability, and conceptualization), a quick and
      thorough examination of the patient's mental status can be performed.

PMID- 2001661
TI  - Depression and suicide assessment.
AB  - Depressed patients and suicidal patients are common Emergency Department patrons
      with the potential for serious morbidity or death. Dysphoric mood, vegetative
      symptoms, and negative perceptions of oneself, the environment, and the future
      are characteristic of depression. Often, the patient is unaware of the depression
      and presents with a variety of somatic complaints, chronic fatigue, or pain
      syndromes. In these instances, the physician must consider the diagnosis of
      depression and ask the patient about any history of depressive symptoms. In all
      depressed patients, a careful history and physical examination are needed to
      identify any drugs or concurrent medical illnesses which might cause or
      exacerbate the depression. If depression is suspected or if the patient presents
      after a suicide attempt, then a thorough evaluation of suicide potential is
      mandatory. Several risk factors for completed suicide exist. Male sex, age under
      19 or over 45, few social supports, and a history of previous suicide attempts
      are all factors associated with increased suicide rates. Concurrent chronic or
      severe medical illnesses and certain psychiatric illnesses, notably depression,
      schizophrenia, and substance abuse, also increase an individual's risk for
      suicide. The method of suicide attempt and the chance for rescue must also be
      considered when determining risk as well as the presence of an organized plan.
      Acute psychosis in the suicidal patient is an ominous finding and these patients
      should be admitted to the hospital. The physician must adopt an empathetic and
      nonjudgmental attitude when caring for potentially suicidal patients. Disposition
      can be determined after careful evaluation of risk factors, circumstances
      surrounding the attempt, and the patient's current feelings. Consultation with a
      psychiatrist or another mental health professional is desirable for any
      potentially suicidal patient. Many such patients can be safely treated as
      outpatients with proper referral; certain high-risk individuals will need to be
      admitted to the hospital. The decision to either hospitalize or discharge can be
      difficult and the emergency physician should admit the patient if doubt exists.

PMID- 2001662
TI  - Acute psychosis. Functional versus organic.
AB  - Acute psychosis is a true emergency and is a manifestation of multiple organic
      and functional disorders. The emergency medicine physician's role in dealing with
      the acutely psychotic patient is to control the patient's behavior, to delineate
      the etiology of the psychosis, and to provide appropriate initial treatment and
      disposition. When making initial contact with the psychotic patient, behavioral
      control can be accomplished through supportive, physical, or pharmacologic
      interventions. Judicious use of rapid tranquilization permits rapid control of
      these patients when supportive and other nonpharmacologic therapies fail. Initial
      examination is directed at identifying immediate life-threatening organic
      disorders and promptly treating them. Historical data, mental status examination,
      physical examination, and appropriate radiologic and laboratory investigations
      give information that assist in delineating functional from organic psychosis.
      Most acute organic psychoses, with the exception of some drug intoxications that
      clear in the Emergency Department, require medical or surgical admission. Acute
      functional psychotic patients who are a danger to themselves or others, who are
      without a reliable social support system, or who present with their first
      psychotic episode require admission to the psychiatric service for further
      evaluation and treatment.

PMID- 2001663
TI  - The somatic patient.
AB  - A significant proportion of patients seen in the Emergency Department will
      present with somatic complaints for which there is no apparent physiologic cause.
      Such patients may be divided into two broad categories: (1) those with symptoms
      and signs consciously synthesized by the patient, either for obvious secondary
      gain (malingering) or as a result of more subtle and complex motivations
      (factitious disorders); and (2) those patients with symptoms that are the
      unconscious expression of psychological stress (somatoform disorders). The
      somatoform disorders include (1) somatization disorder (characterized by a
      chronic history of numerous and widely divergent somatic complaints), (2)
      psychogenic pain disorder (somatization expressed in terms of persistent pain),
      (3) hypochondriasis (a conviction that one is diseased and disabled in
      conjunction with a well-focused constellation of supporting symptoms), and (4)
      conversion disorder (a single, usually nonpainful neurologic symptom, often with
      identifiable coping value for the patient). The first three disorders have been
      aggregately termed the "common somatization syndrome." Management of the
      somatically focused patient includes the communication of a caring attitude to
      the patient in conjunction with a cautious and diligent search for treatable
      medical or psychiatric illness. Resocialization and development of patient links
      with ongoing, nurturing nonmedical as well as medical support systems is of
      benefit.

PMID- 2001664
TI  - Anxiety.
AB  - The general principles useful in approaching most psychiatric emergencies are
      equally applicable to the handling of the anxious patient. Establish rapid
      contact because anxious patients should not be left waiting. Expedite talking to
      reduce tension because putting thoughts and emotions into words invariably
      reduces initial tension. Make a quick first assessment of the anxious patient's
      general appearance, level of consciousness, level of tension, and leading affect
      or mood. Choose a private and relaxed setting for the interview if possible.
      Allow for a slow final evaluation because many initially overwhelmed anxious
      people may reconstitute within a matter of hours when allowed to talk, rest, or
      even sleep. Take the anxious patient's chief complaint seriously. A brief
      physical examination should be performed routinely in almost all cases,
      especially when there is a physical complaint. Every attempt should be made to
      rule out an organic etiology for the anxiety. Listening is an active but
      demanding process. Most of the time it means sitting down and giving all of one's
      attention to the patient, even if it is for just a few minutes. What patients
      find most comforting is the feeling of being understood. The emergency medicine
      physician should be careful to avoid a judgmental or punitive approach. Every
      attempt should be made to engage the family in caring for the patient while in
      the Emergency Department. It is equally important to recognize that relatives and
      friends may need assistance to help cope with the anxious patient once
      discharged. The emergency medicine physician needs to assess the degree of social
      support available in the patient's environment because a sensible disposition
      will depend on it.

PMID- 2001665
TI  - Family grief in the emergency department.
AB  - Emergency physicians frequently face death, yet many are unprepared to deal with
      the family survivors of a patient who has died unexpectedly. Without the benefit
      of establishing prior rapport with the family, the emergency physician must
      anticipate the family's grief response so that he or she can intervene to avoid
      an unnecessarily prolonged or morbid grief reaction. Factors predisposing to a
      pathologic grief response in the death of a spouse or of an infant or child must
      be recognized, and the physician's power to assuage survivor guilt should be
      used. Certain key actions in the process of notifying survivors, viewing the
      body, concluding the emergency department visit, and following up after the
      patient's death help facilitate survivor grief in the least traumatic way
      possible. Emergency Departments can improve their dealing with death by
      instituting a team approach using doctors, nurses, social workers, and clergy to
      better support family members in their emergency department experience and to
      provide a link with community service organizations helpful to the family after
      they leave the hospital.

PMID- 2001666
TI  - Psychological reaction to hospitalization and illness in the emergency
      department.
AB  - Each personality type presents with different methods of coping. Physicians
      should be aware of the impact on a patient's psychological functioning and
      ability to cope with illness and hospitalization, to understand and more
      effectively manage the patient. The physician must try to assess the patient's
      baseline personality from their past and present behavior. Establishing a good
      physician-patient relationship is important as a source of information about
      behavior of patients and how they will respond to their illness. Depending on the
      specific personality type, each patient will respond differently to the stress of
      illness. The effort of the emergency physician to identify personality types will
      aid in medical management of the patient and enable the physician to help each
      patient cope effectively with the illness and the hospitalization. The specific
      issues that seem to be threatening to traumatized patients include the following:
      helplessness, humiliation, blurring of body image, and gaps in memory filled with
      distortions. The traumatized patient experiences an altered state of
      consciousness which is either due to a physiologic cause or an emotional cause.
      Emotional causes are usually based on defensive dissociation. People who have
      been in an auto accident characteristically report loss of memory of the intense
      pain that the accident produces initially. Oftentimes, the core experience for
      the traumatic patient is not somatic, it is unconscious. The interesting feature
      is that so many patients do not remember the accident. The mind seems to be
      filled with all kinds of distortions and irrelevant and perhaps totally
      inconsistent fantasies, such as imprisonment, confinement, or deathlike
      experiences. Some report that they are being incarcerated, others recall being in
      a featureless cubicle with no contact with the normal world in which there are no
      windows, no pictures, no flowers. Others remember only being surrounded by
      masked, hatted, uniformed wardens who are standing over them with nasogastric
      tubes, intravenous lines, Foley catheters, arterial blood gases, subclavians, and
      dermal cut-downs. This is an overwhelming nightmare that can be relieved only by
      the empathic and caring physician and emergency department staff. The stress of
      medical illness and/or hospitalization can be overwhelming for some patients and
      is usually followed by some form of psychological response. Current understanding
      of the psychological impact of illness is based upon psychological defenses,
      coping mechanisms, and individual personality. It is the ability of the emergency
      physician to identify defenses, coping skills and personality types that will aid
      him or her in the medical management of the patients in their time of illness and
      hospitalization.

PMID- 2001667
TI  - Crisis intervention in the emergency department.
AB  - The word crisis implies a challenge to the personality, family, and community
      created by an altered set of circumstances for which adaptive resources are not
      readily available. It has long been recognized that mastery of a crisis can
      result in an enrichment of the personality, which then acquires resources to deal
      with similar events in the future. Failure to meet the challenge results not
      infrequently in a maladaptive response, which, too, is likely to be applied to
      similar challenges in the future--thereby burdening the personality with a
      handicap. Intervention in crisis aims at assisting the individual toward meeting
      his or her crisis successfully, and at times entails little more than guidance,
      advice, or education. When analyzed more adequately, intervention implies an
      evaluation of the resources within the individual, an evaluation of the resources
      among those who surround the individual in the family and the community, and an
      assessment of his or her past personal history. This takes into account how the
      individual has handled previous crises in his life; educational, vocational,
      marital, and social achievements; preferences; values; and what he or she expects
      from professional help. The individual is then invited, with those around him and
      involved with him, to examine the strengths that are available to him and to
      participate where possible in planning the steps immediately necessary for the
      successful resolution of the crisis.

PMID- 2001668
TI  - Drug-induced psychoses.
AB  - Major causes of drug-induced psychoses include cocaine, amphetamines,
      phencyclidine, cannabinoids, LSD, mescaline, the so-called designer drugs,
      anticholinergic compounds, and steroids. Most drug-induced psychoses are managed
      with general supportive measures, reassurance, minimizing patient stimulation,
      and benzodiazepines as needed; however, specific antidotes such as physostigmine
      for anticholinergic poisoning or urinary acidification to enhance excretion of
      amphetamines or phencyclidine may be indicated in some patients. Any patient with
      a drug-induced psychosis must be evaluated carefully for evidence of other toxic
      effects of the drug in question.

PMID- 2001669
TI  - Triage of disaster-related neuropsychiatric casualties.
AB  - Existing triage algorithms consider, for the most part, only the primary casualty
      with physical trauma. Algorithms fail to appreciate the primary, secondary, or
      tertiary neuropsychiatric casualty. Research advances on neuropsychiatric
      casualties must link with the mandates of emergency medical services and disaster
      management to improve triage sensitivity and specificity. Early recognition and
      management of neuropsychiatric casualties will diminish the potential for long
      term consequences. Expanded triage algorithm supplements are proposed to improve
      the recognition of those victims at risk.

PMID- 2001670
TI  - An analysis of the origin of metazoans, using comparisons of partial sequences of
      the 28S RNA, reveals an early emergence of triploblasts.
AB  - In order to study the origin of metazoans, we have compared sequences from the 5'
      end of the large subunit ribosomal RNA of a number of protists, fungi, plants and
      metazoans, including all diploblastic phyla (sequences of 10 new species have
      been determined, including that of the placozoan, Trichoplax adhaerens). These
      sequences were analyzed using distance matrix, maximum parsimony and maximum
      likelihood methods, and the validity of the results was ascertained with
      bootstrapping and species removal or addition. Triploblasts and diploblasts
      formed two clearly separated monophyletic units; this divergence, which
      apparently preceded the diversification of diploblastic animals (i.e. the
      successive sponge, ctenophore, cnidarian radiations), showed a much more ancient
      origin of triploblasts with respect to diploblasts than classically assumed.
      These results do not exclude the possibility that triploblasts and diploblasts
      arose independently from different protists.

PMID- 2001671
TI  - Time-resolved X-ray diffraction study of structural changes associated with the
      photocycle of bacteriorhodopsin.
AB  - The time course of structural changes accompanying the transition from the M412
      intermediate to the BR568 ground state in the photocycle of bacteriorhodopsin
      (BR) from Halobacterium halobium was studied at room temperature with a time
      resolution of 15 ms using synchrotron radiation X-ray diffraction. The M412 decay
      rate was slowed down by employing mutated BR Asp96Asn in purple membranes at two
      different pH-values. The observed light-induced intensity changes of in-plane X
      ray reflections were fully reversible. For the mutated BR at neutral pH the
      kinetics of the structural alterations (tau 1/2 = 125 ms) were very similar to
      those of the optical changes characterizing the M412 decay, whereas at pH 9.6 the
      structural relaxation (tau 1/2 = 3 s) slightly lagged behind the absorbance
      changes at 410 nm. The overall X-ray intensity change between the M412
      intermediate and the ground state was about 9% for the different samples
      investigated and is associated with electron density changes close to helix G, B
      and E. Similar changes (tau 1/2 = 1.3-3.6 s), which also confirm earlier neutron
      scattering results on the BR568 and M412 intermediates trapped at -180 degrees C,
      were observed with wild type BR retarded by 2 M guanidine hydrochloride (pH 9.4).
      The results unequivocally prove that the tertiary structure of BR changes during
      the photocycle.

PMID- 2001672
TI  - Identification of the structural gene for glucose-6-phosphate dehydrogenase in
      yeast. Inactivation leads to a nutritional requirement for organic sulfur.
AB  - Cloning of the MET19 gene revealed that it encodes the glucose-6-phosphate
      dehydrogenase from yeast. Sequence analysis showed a high degree of similarity
      between the yeast and the human enzymes. The cloned gene has allowed the
      construction of a glucose-6-phosphate dehydrogenase null mutant. The only
      phenotype of such a strain is an absolute requirement for an organic sulfur
      source, i.e. methionine, S-adenosylmethionine (AdoMet), cysteine, glutathione or
      homocysteine. The phenotype of this null mutant raises some new questions about
      the exact functions of the pentose phosphate pathway which was usually considered
      as the main cellular source of NADPH. Moreover, results reported here show that
      an increase of the AdoMet pool represses the transcription of the glucose-6
      phosphate dehydrogenase gene. This regulation acts on the glucose-6-phosphate
      dehydrogenase biosynthesis but does not affect the synthesis of 6
      phosphogluconate dehydrogenase. That AdoMet controls a part of the pentose
      phosphate pathway sheds new light on mechanisms regulating the relative fluxes of
      carbon utilization through the pentose phosphate pathway and glycolysis.

PMID- 2001673
TI  - Proteinase yscE, the yeast proteasome/multicatalytic-multifunctional proteinase:
      mutants unravel its function in stress induced proteolysis and uncover its
      necessity for cell survival.
AB  - Proteinase yscE is the yeast equivalent of the proteasome, a multicatalytic
      multifunctional proteinase found in higher eukaryotic cells. We have isolated
      three mutants affecting the proteolytic activity of proteinase yscE. The mutants
      show a specific reduction in the activity of the complex against peptide
      substrates with hydrophobic amino acids at the cleavage site and define two
      complementation groups, PRE1 and PRE2. The PRE1 gene was cloned and shown to be
      essential. The deduced amino acid sequence encoded by the PRE1 gene reveals weak,
      but significant similarities to proteasome subunits of other organisms. Two
      dimensional gel electrophoresis identified the yeast proteasome to be composed of
      14 different subunits. Comparison of these 14 subunits with the translation
      product obtained from PRE1 mRNA synthesized in vitro demonstrated that PRE1
      encodes the 22.6 kd subunit (numbered 11) of the yeast proteasome. Diploids
      homozygous for pre1-1 are defective in sporulation. Strains carrying the pre1-1
      mutation show enhanced sensitivity to stresses such as incorporation of the amino
      acid analogue canavanine into proteins or a combination of poor growth medium and
      elevated temperature. Under these stress conditions pre1-1 mutant cells exhibit
      decreased protein degradation and accumulate ubiquitin-protein conjugates.

PMID- 2001674
TI  - Proofreading in vivo: editing of homocysteine by methionyl-tRNA synthetase in the
      yeast Saccharomyces cerevisiae.
AB  - Homocysteine thiolactone is a product of an error-editing reaction, catalyzed by
      Escherichia coli methionyl-tRNA synthetase, which prevents incorporation of
      homocysteine into tRNA and protein, both in vitro and in vivo. Here, the
      thiolactone is also shown to occur in cultures of the yeast Saccharomyces
      cerevisiae. In yeast, the thiolactone is made from homocysteine in a reaction
      catalyzed by methionyl-tRNA synthetase. One molecule of homocysteine is edited as
      thiolactone per 500 molecules of methionine incorporated into protein.
      Homocysteine, added exogenously to the medium or overproduced by some yeast
      mutants, is detrimental to cell growth. The cost of homocysteine editing in yeast
      is minimized by the presence of a pathway leading from homocysteine to cysteine,
      which keeps intracellular homocysteine at low levels. These results not only
      directly demonstrate that editing of errors in amino acid selection by methionyl
      tRNA synthetase operates in vivo in yeast but also establish the importance of
      proofreading mechanisms in a eukaryotic organism.

PMID- 2001675
TI  - Transcription of the Xenopus laevis selenocysteine tRNA(Ser)Sec gene: a system
      that combines an internal B box and upstream elements also found in U6 snRNA
      genes.
AB  - The transcription mode of the Xenopus tRNA(Ser)Sec gene by RNA polymerase III was
      deciphered by injection of mutant templates into Xenopus oocyte nuclei.
      tRNA(Ser)Sec represents the paradigm of a new class of RNA polymerase III genes
      combining tRNA and U snRNA gene regulatory elements. Its promoter is tripartite,
      constituted by two upstream elements, a PSE and a TATA motif that are
      interchangeable with those of U6 snRNA genes and an internal box B as in other
      tRNAs. The B box enables the transcription level dependent on the upstream
      promoter to be increased. Data obtained indicate that U1 snRNA (Pol II) and
      tRNA(Ser)Sec (Pol III) genes share at least one transcription factor, implying
      that the border between transcription systems is less tight than expected.

PMID- 2001676
TI  - Transcription-induced nucleosome 'splitting': an underlying structure for DNase I
      sensitive chromatin.
AB  - Utilizing yeast strains containing promoter mutations, we demonstrate that
      transcription of the HSP82 gene causes nucleosomes toward the 3'-end to become
      DNase I sensitive and 'split' into structures that exhibit a 'half-nucleosomal'
      cleavage periodicity. Splitting occurs even when only a few RNA polymerase II
      molecules are engaged in basal level transcription or during the first round of
      induced transcription. The split nucleosomal structure survives nuclear isolation
      suggesting that it may be stabilized by post-translational modifications or non
      histone proteins, and may require DNA replication for reversal to a whole
      nucleosomal structure. Split nucleosomes represent a structure for DNase I
      sensitive chromatin and are probably of common occurrence but difficult to detect
      experimentally. We suggest that transient positive supercoils downstream of
      traversing RNA polymerase lead to nucleosome splitting.

PMID- 2001677
TI  - The maize regulatory locus Opaque-2 encodes a DNA-binding protein which activates
      the transcription of the b-32 gene.
AB  - The maize locus, Opaque-2, controls the expression in developing endosperm of
      structural genes encoding a family of storage proteins, the 22 kd zeins, and an
      abundant albumin, termed b-32. It is shown that the promoter of the b-32 gene is
      activated in vivo in the presence of the O2 gene product and that the information
      necessary for this activation resides in a 440 bp DNA fragment containing five O2
      binding sites (GATGAPyPuTGPu). Two of these sites are embedded in copies of the
      'endosperm box', a motif thought to be involved in endosperm-specific expression,
      which is also represented in 22 kd zein promoters. The O2 protein is also shown
      to be capable of binding in vitro and activating in vivo, its own promoter.

PMID- 2001678
TI  - Methylation and proteolysis are essential for efficient membrane binding of
      prenylated p21K-ras(B).
AB  - Plasma membrane targeting of p21K-ras(B) requires a CAAX motif and a polybasic
      domain. The CAAX box directs a triplet of post-translational modifications:
      farnesylation, proteolysis of the AAX amino acids and methylesterification. These
      modifications are closely coupled in vivo. However, in vitro translation of mRNA
      in rabbit reticulocyte lysates produces p21K-ras(B) proteins which are arrested
      in processing after farnesylation. Intracellular membranes are then required both
      for proteolytic removal of the AAX amino acids and methylesterification of
      farnesylated p21K-ras(B). Binding of p21K-ras(B) to plasma membranes in vitro can
      then be shown to depend critically on AAX proteolysis and methylesterification
      since p21K-ras(B) which is farnesylated, but not methylated, binds inefficiently
      to membranes.

PMID- 2001679
TI  - Repression of the Drosophila fushi tarazu (ftz) segmentation gene.
AB  - The striped expression of the Drosophila segmentation gene fushi tarazu in
      alternate parasegments of the early embryo is controlled by the 740 bp zebra
      element. Among multiple protein factors that bind to the zebra element, FTZ-F2
      behaves as a transcriptional repressor of ftz. Point mutations in the zebra
      element which disrupt FTZ-F2 binding to DNA cause ectopic expression of zebra
      lacZ activity in transformed embryos. The mutant constructs are expressed from
      the zygotic genome in preblastoderm embryos as early as the third nuclear
      division cycle. This unprecedented early transcription suggests that ftz requires
      active repression during initial nuclear division cycles, a novel type of
      embryonic gene regulation. A putative FTZ-F2 cDNA clone isolated by recognition
      site screening of an expression library was found to be identical in sequence
      with the zinc finger protein tramtrack (Harrison and Travers, 1990).

PMID- 2001680
TI  - Regulation of the acetate operon in Escherichia coli: purification and functional
      characterization of the IclR repressor.
AB  - Growth of Escherichia coli on acetate requires operation of the anaplerotic
      sequence known as the glyoxylate bypass. In this pathway three different enzymes
      are activated: malate synthase, isocitrate lyase and isocitrate dehydrogenase
      kinase/phosphatase which are encoded by genes aceB, aceA and aceK, respectively.
      These three genes are clustered, in that order, in the same acetate (ace) operon
      whose expression is under the transcriptional control of the iclR gene located
      downstream from aceK. We have cloned the iclR gene in the pKK233-2 vector which
      allows optimization of both transcription and translation initiation. The IclR
      repressor has been overproduced, then purified to homogeneity in a one-step
      procedure by cation exchange chromatography after ammonium sulfate fractionation.
      Its specific interaction with the operator/promoter region of the ace operon has
      been analyzed by gel retardation and DNase I footprinting experiments. The IclR
      repressor has been shown to recognize a 35 bp palindromic sequence which largely
      overlaps the -35 recognition site of RNA polymerase. Moreover, the formation of
      the complex between IclR and the operator/promoter region has been found to be
      impaired by phosphoenol pyruvate but insensitive to acetate, acetyl-CoA,
      pyruvate, and oxaloacetate. These results are discussed in terms of primary
      regulation of the expression of the ace operon.

PMID- 2001681
TI  - Genetic control of sex-dependent meiotic recombination in the major
      histocompatibility complex of the mouse.
AB  - Meiotic recombination within the proximal region of the major histocompatibility
      complex (MHC) of the mouse is not random but occurs in clusters at certain
      restricted sites, so-called recombinational hotspots. The wm7 haplotype of the
      MHC, derived from the wild mouse, enhances recombination specifically during
      female meiosis within a fragment of 1.3 kb of DNA located between the A beta 3
      and A beta 2 genes in genetic crosses with laboratory haplotypes. Previous
      studies revealed no significant strain differences in nucleotide sequences around
      the hotspot, irrespective of the ability of the strain to enhance the
      recombination. It appeared that a distant genetic element might, therefore,
      control the rate of recombination. In the present study, original recombinants
      whose breakpoints were defined by direct sequencing of PCR-amplified DNAs were
      tested for the rate of secondary recombination in the crosses with laboratory
      strains in order to determine the location of such a genetic element. The results
      clearly demonstrated that the chromosomal segment proximal to the hotspot is
      essential for enhancement of recombination. Moreover, the male recombination is
      suppressed by a segment distal to the hotspot.

PMID- 2001682
TI  - HU and IHF, two homologous histone-like proteins of Escherichia coli, form
      different protein-DNA complexes with short DNA fragments.
AB  - Using the gel retardation technique we have studied the protein-DNA complexes
      formed between HU--the major histone-like protein of Escherichia coli--and short
      DNA fragments. We show that several HU heterodimers bind DNA in a regularly
      spaced fashion with each heterodimer occupying about 9 base pairs. The alpha 2
      and beta 2 HU homodimers form the same structure as the alpha beta heterodimer on
      double stranded DNA. However when compared to the heterodimer, they bind single
      stranded DNA with higher affinity. We also show that HU and the Integration Host
      Factor of E. coli (IHF) form different structures with the same DNA fragments.
      Moreover, HU seems to enhance the DNA-binding capacity of IHF to a DNA fragment
      which does not contain its consensus sequence.

PMID- 2001683
TI  - T-DNA integration: a mode of illegitimate recombination in plants.
AB  - Transferred DNA (T-DNA) insertions of Agrobacterium gene fusion vectors and
      corresponding insertional target sites were isolated from transgenic and wild
      type Arabidopsis thaliana plants. Nucleotide sequence comparison of wild type and
      T-DNA-tagged genomic loci showed that T-DNA integration resulted in target site
      deletions of 29-73 bp. In those cases where integrated T-DNA segments turned out
      to be smaller than canonical ones, the break-points of target deletions and T-DNA
      insertions overlapped and consisted of 5-7 identical nucleotides. Formation of
      precise junctions at the right T-DNA border, and DNA sequence homology between
      the left termini of T-DNA segments and break-points of target deletions were
      observed in those cases where full-length canonical T-DNA inserts were very
      precisely replacing plant target DNA sequences. Aberrant junctions were observed
      in those transformants where termini of T-DNA segments showed no homology to
      break-points of target sequence deletions. Homology between short segments within
      target sites and T-DNA, as well as conversion and duplication of DNA sequences at
      junctions, suggests that T-DNA integration results from illegitimate
      recombination. The data suggest that while the left T-DNA terminus and both
      target termini participate in partial pairing and DNA repair, the right T-DNA
      terminus plays an essential role in the recognition of the target and in the
      formation of a primary synapsis during integration.

PMID- 2001684
TI  - Cleavage of a four-way DNA junction by a restriction enzyme spanning the point of
      strand exchange.
AB  - The four-way DNA junction is believed to fold in the presence of metal ions into
      an X-shaped structure, in which there is pairwise coaxial stacking of helical
      arms. A restriction enzyme MboII has been used to probe this structure. A
      junction was constructed containing a recognition site for MboII in one helical
      arm, positioned such that stacking of arms would result in cleavage in a
      neighbouring arm. Strong cleavage was observed, at the sites expected on the
      basis of coaxial stacking. An additional cleavage was seen corresponding to the
      formation of an alternative stacking isomer, suggesting that the two isomeric
      forms are in dynamic equilibrium in solution.

PMID- 2001686
TI  - Childhood appendicitis: factors associated with its incidence and perforation in
      Ethiopian children.
AB  - Acute appendicitis is a common paediatric emergency necessitating surgical
      intervention. Factors contributing to the incidence of the disease and
      appendiceal perforation in all children with acute appendicitis admitted to the
      Ethio-Swedish Children's Hospital in Addis Abeba, Ethiopia from Jan 1983 to
      December 1987 were studied. There were a total of 278 cases of appendicitis, with
      matched controls, seen. The incidence of perforation was 67%. Statistically
      significant differences between cases and controls were seen for the educational
      status of the parents (p less than .001), the parental income (p less than .001)
      and the nutritional status of the patient (p less than .001). The risk of
      perforation increased with increased duration of the illness. Perforation was
      common in children with normal height and better parental education. The
      incidence of appendicitis appears to be related to improved socioeconomic status.
      Prospective studies to examine this and other associations are warranted.

PMID- 2001685
TI  - Formation of a thermodynamically metastable structure containing hairpin II is
      critical for infectivity of potato spindle tuber viroid RNA.
AB  - The functional relevance of a hairpin II-containing structure of viroid RNA was
      studied by site-directed mutagenesis, thermodynamic calculations, experimental
      denaturation curves and infectivity tests. Hairpin II is formed during thermal
      denaturation of circular viroids or as part of a metastable structure during
      synthesis of viroid replication intermediates. In potato spindle tuber viroid
      (PSTVd), eight single-site mutations were generated in the segments which form
      hairpin II. From the mutated viroid cDNA clones, linear RNA transcripts of PSTVd
      unit length were synthesized. The relevance of hairpin II for the mechanism of
      denaturation was confirmed quantitatively by optical denaturation curves and
      temperature-gradient gel electrophoresis. Infectivity tests showed that the
      mutations in the core region of hairpin II reverted to the wild type sequence
      whereas the mutations in the peripheral regions of hairpin II remained
      genetically stable. These data are in accordance with the natural variance of
      hairpin II in other viroids of the PSTVd class. Thus, the integrity of the core
      of hairpin II is critical for infectivity. Hairpin II exhibits a strong
      similarity in sequence as well as in three-dimensional structure to certain DNA
      GC-clusters found in the 5'-upstream regions of some genes in man, animals,
      viruses and plants. A hypothesis about a function of hairpin II as a binding site
      for host cell transcription factors is proposed.

PMID- 2001687
TI  - Clinical and laboratory features of severe and complicated falciparum malaria the
      experience from Gonder Hospital.
AB  - Over a period of 6 months in 1988, 104 patients with severe and complicated
      falciparum malaria were admitted to the Gonder College Hospital (GCH), Gonder,
      Ethiopia; 85 male (81.7%) and 19 female (18.3%). The age ranged between 14 and 70
      years with a mean age of 31 years. Eighty-one patients (78.3%) had moved from a
      nonendemic to a malariaendemic area shortly before their illness. Altered state
      of consciousness, hyperparasitaemia and severe anaemia were the most frequent
      complications found. Fifty-three patients (51.0%) died. Non-immune status and
      unknown duration of symptoms were significantly associated with mortality. Among
      those who died, comatose state on admission, hyperparasitaemia and acute renal
      failure were more frequently seen. Forty-six (86.8%) had developed two or more
      complications and 15 (28.3%) had superimposed bacterial infections. Inadequate
      preventive measures and treatment facilities may be two important factors
      accounting for the high mortality.

PMID- 2001688
TI  - Simultaneous appendectomy and inguinal herniorrhaphy could be beneficial.
AB  - Two patients seen in Murtala Muhammed Hospital in Kano, Nigeria in 1989, who
      developed acute appendicitis after inguinal hernia repair during which the
      appendices were present in the hernia sacs but not removed, are described. Eleven
      patients who had an appendectomy during inguinal hernia repair are also
      described. None had a wound infection or recurrence of their hernia. Because of
      the possibility that postoperative adhesions in the vicinity of the appendix
      might subsequently provoke inflammation, it is suggested that an adequately
      exposed appendix in an inguinal hernia sac be routinely removed.

PMID- 2001689
TI  - Neurological decompression sickness.
AB  - A middle-aged professional diver with neurological decompression sickness, seen
      in Tikur Anbessa Hospital, Addis Abeba, in February 1989, is reported. Early
      recognition and prompt treatment, and, most of all, prevention are of paramount
      importance to avoid permanent neurological deficits.

PMID- 2001690
TI  - Klippel-Feil syndrome in two Ethiopian children.
AB  - Klippel-Feil syndrome or congenital short neck is a rare malformation in which
      there is congenital fusion of two or more vertebrae in the cervical region. In
      some patients it is associated with other congenital malformations in the
      skeleton, lung and heart. Two cases of Klippel-Feil syndrome in children who also
      had cardiovascular malformations are described and the literature is reviewed.

PMID- 2001691
TI  - Cellobiose oxidase from Phanerochaete chrysosporium can be cleaved by papain into
      two domains.
AB  - Cellobiose oxidase from the white rot fungus Phanerochaete chrysosporium has been
      purified to homogeneity by a new method. The enzyme has been cleaved by papain
      into two fragments: one containing the heme group and one containing the flavin
      group. The flavin fragment can oxidize cellobiose and is reoxidized by oxygen.
      Cellobiose oxidase binds to cellulose to approximately the same extent as
      cellobiohydrolase I. The cellulose-binding site is located on the flavin domain.
      The enzyme cannot be totally displaced from cellulose by cellobiose, and it is
      still active when adsorbed to cellulose. The possible role of the enzyme in
      lignocellulose degradation is discussed.

PMID- 2001692
TI  - Exopolysaccharide structure from Bacillus circulans.

PMID- 2001693
TI  - Primary structure of O-linked carbohydrate chains in the cellulosome of different
      Clostridium thermocellum strains.
AB  - The cell-free forms of the multiple cellulase-containing protein complex
      (cellulosome), isolated from the cellulolytic bacterium Clostridium thermocellum
      strains YS, ATCC 27405 and LQRI, have a total carbohydrate content of 5-7% (by
      mass), consisting of O-linked oligosaccharide chains. The carbohydrate chains
      were liberated by alkaline-borohydride treatment and fractionated as
      oligosaccharide alditols via gel-permeation chromatography and HPLC. The
      fractions were investigated by 500-MHz 1H-NMR spectroscopy in combination with
      monosaccharide and methylation analysis and with fast-atom-bombardment mass
      spectrometry (FAB-MS). In addition to the previously described major
      oligosaccharide, (formula; see text) [Gerwig, G. J., de Waard, P., Kamerling, J.
      P., Vliegenthart, J. F. G., Morgenstern, E., Lamed, R. & Bayer, E. A. (1989) J.
      Biol. Chem. 264, 1027-1035], the following partial structures of this compound
      could be established: (formula; see text). Cell-free and cell-associated forms of
      the cellulosome of C. thermocellum, as determined for strain YS, have the same
      oligosaccharide pattern. Based on the oligosaccharide structures, a biosynthetic
      pathway is suggested.

PMID- 2001694
TI  - Investigation of the membrane-active peptides melittin and glucagon by
      photochemically induced dynamic-nuclear-polarization (photo-CIDNP) NMR.
AB  - The photochemically induced dynamic-nuclear-polarization (photo-CIDNP) NMR
      technique was used to investigate the membrane-active peptides melittin and
      glucagon. The experiments were performed both in the absence and presence of
      phospholipid vesicles in order to study the topography of the membrane-bound
      state. From the results it can be concluded that the melittin peptide chain is
      oriented in such a way that the single tryptophan residue (Trp19) reaches into
      the membrane. In the case of glucagon, a binding interaction with vesicle
      membranes is indicated within the pH range 2-10, whereby the single tryptophan
      residue (Trp25) is buried in the lipid bilayer and the tyrosine and histidine
      residues are exposed to the aqueous solvent.

PMID- 2001695
TI  - Processing of the precursor of protamine P2 in mouse. Identification of
      intermediates by their insolubility in the presence of sodium dodecyl sulfate.
AB  - Two basic proteins, protamines P1 and P2, are present in chromatin of mouse
      spermatozoa. Protamine P1, the less abundant protein in mouse, has a homolog in
      most mammals, and its synthesis follows a conventional route. In contrast,
      protamine P2 has been found only in certain other mammals, including humans, and
      it is synthesized as a precursor nearly twice as long as the mature protein.
      Processing of this precursor is not yet understood, although it necessarily takes
      place in elongating spermatids and is likely to play a role in the chromatin
      condensation occurring in these haploid cells. We have fractionated basic
      proteins from mouse testis chromatin and have identified six proteins on
      electrophoretic gels which, like protamines, are insoluble in SDS. All six were
      also soluble at the same trichloroacetic acid concentration as protamine P2 and
      were present in chromatin of elongating spermatids. Radioactive labelling
      patterns acquired by these SDS-insoluble proteins during translation in vitro of
      testis RNA indicate that the largest represents the precursor of protamine P2,
      and suggest that the others represent intermediates generated by proteolytic
      cleavage of the precursor. Results from pulse 3H labelling in vivo were also
      consistent with the conclusion that a precursor/product relationship exists
      between these proteins and protamine P2. Conclusions concerning the kinetics of
      processing have, in addition, been drawn from this data. Hypotheses concerning
      possible functional roles played by the precursor are presented.

PMID- 2001696
TI  - Molecular cloning and sequence analysis of bovine lactotransferrin.
AB  - The screening of a bovine submaxillary gland cDNA library yielded 25 clones
      coding for bovine lactotransferrin. The nucleotide sequence of the longest insert
      contained a protein-coding region of 2115 nucleotides and a 3' non-coding region
      of 194 nucleotides followed by a poly(A) tract of about 55 nucleotides. The
      predicted peptide sequence included a 16-amino-acid signal sequence upstream of
      the first amino acid of the native protein. The identity of the clone was
      confirmed by matching the amino acid sequence predicted from the cDNA with the N
      terminal and tryptic peptide sequences derived from purified bovine milk
      lactotransferrin, and also by similarity with human and murine lactotransferrins.
      The cDNA described corresponds to a 705-amino-acid-long preprotein that lacks the
      start methionine. The sequence of the secreted protein is 689 amino acids long
      and contains five potential glycosylation sites. Bovine lactotransferrin is 69%
      and 64% identical to human and murine lactotransferrins, respectively.

PMID- 2001697
TI  - Protein O-glycosylation in Saccharomyces cerevisiae. Purification and
      characterization of the dolichyl-phosphate-D-mannose-protein O-D
      mannosyltransferase.
AB  - The enzyme dolichyl-phosphate-D-mannose:protein O-D-mannosyltransferase has been
      solubilized from Saccharomyces cerevisiae membranes and its mannosyltransferase
      activity demonstrated using short peptides. The specific activity of the protein
      was enriched 130-fold before it was further purified by native and SDS gel
      chromatography. A 92-kDa band correlated well with the enzyme activity; an
      antibody raised against this protein precipitated the mannosyltransferase. The 92
      kDa band was hydrolysed to 84 kDa after treatment with endoglycosidase F,
      indicating that the protein is a glycoprotein which may contain four carbohydrate
      chains. The purified mannosyltransferase is distinctly influenced in transfer
      specificity by amino acids next to serine and threonine within the acceptor
      peptides. Thus acidic amino acids strongly inhibit acceptor activity as do
      glycine and proline residues as amino-terminal and carboxy-terminal neighbours,
      respectively.

PMID- 2001698
TI  - Core region of Citrobacter O23 lipopolysaccharide. Structure elucidation by
      chemical methods, gas chromatography/mass spectrometry and NMR spectroscopy at
      500 MHz.
AB  - A novel enterobacterial core region in Citrobacter O23 lipopolysaccharide is
      described. Its structure was determined by methylation analysis/mass
      spectrometry, chemical degradation and one- and two-dimensional 1H-NMR
      spectroscopy: [formula; see text] where PPEtN stands for
      diphosphorylethanolamine, and dOclA for 3-deoxy-D-manno-octulosonic acid.

PMID- 2001699
TI  - Biochemical, cytotoxic and pharmacokinetic properties of an immunotoxin composed
      of a mouse monoclonal antibody Fib75 and the ribosome-inactivating protein alpha
      sarcin from Aspergillus giganteus.
AB  - An immunotoxin was synthesized by the attachment of alpha-sarcin, the ribosome
      inactivating protein derived from the mould Aspergillus giganteus, to a
      monoclonal mouse IgG2 antibody Fib75. The alpha-sarcin immunotoxin exerted toxic
      effects in tissue culture against the EJ human bladder carcinoma cell line,
      expressing the antigen recognised by the Fib75 antibody, inhibiting the
      incorporation of [3H]leucine by 50% at a concentration of 0.46 nM. The cytotoxic
      effects of the alpha-sarcin immunotoxin were indistinguishable from those of a
      Fib75 immunotoxin made with ricin A chain. Fib75-alpha-sarcin was cleared from
      the circulation of the rat with biphasic kinetics following intravenous
      administration. The alpha- and beta-phase half-lives were 0.8 h and 6 h,
      respectively, similar to the serum half-lives of analogous Fib75 immunotoxins
      made with ribosome-inactivating proteins derived from plants. alpha-Sarcin was
      completely stable in physiological saline buffer at 37 degrees C, whereas the
      ribosome-inactivating activity of ricin A chain was gradually lost under
      identical conditions. alpha-Sarcin may be a valuable alternative to ricin A chain
      for the construction of therapeutic immunotoxins because of its smaller size and
      greater thermostability.

PMID- 2001700
TI  - Vitamin A intake and in vivo expression of the genes involved in retinol
      transport.
AB  - Two different metabolic alterations in vitamin A status are known to cause
      changes in the amount of circulating retinol-binding protein (RBP) and cellular
      retinol-binding protein (CRBP) in experimental animals; namely vitamin A
      deficiency, characterized by depleted retinol-liver stores and hypervitaminosis
      A, characterized by hepatic accumulation of retinyl esters. We have induced
      vitamin A deficiency and hypervitaminosis A in two groups of rats with the aim of
      determining whether the expression of the genes coding for these two proteins
      might be directly regulated by retinol. Using human RBP and CRBP cDNAs as probes,
      we measured the rate of transcription of the two genes in liver nuclei from
      control and treated rats by run-on transcription assays, and the steady-state
      level of the mRNAs by Northern blot analysis of total liver RNA. The distribution
      profile of RBP and CRBP mRNAs on fractionated liver polysomes was also examined.
      We have found a threefold decrease in the hepatic level of CRBP mRNA in vitamin-A
      deficient animals, while the RBP mRNA is not affected by this nutritional
      deprivation. The decreases does not correspond to a lower transcription rate of
      the gene and therefore it is likely to result from lower stability of the CRBP
      mRNA. In hypervitaminosis A, we do not observe any differences in both the steady
      state level of the mRNAs and in the rate of transcription of the two genes. The
      results are discussed in terms of retinol-dependent stabilization of the mRNA
      coding for CRBP.

PMID- 2001701
TI  - Actin-caldesmon-myosin-subfragment-1 ternary complex viewed by electron
      microscopy. Competitive actin binding region for caldesmon and myosin subfragment
      1.
AB  - An earlier electron microscopic study using different caldesmon forms complexed
      with actin revealed that the aggregates produced display regular periodic
      striation after antibody labeling of the 35-kDa caldesmon fragment. This approach
      provides further evidence that a caldesmon fragment, even as small as 15 kDa, can
      induce actin filaments to assemble into bundles. The observed difference in the
      compactness of these structures, depending on the use of the 15-kDa fragment
      instead of the 35-kDa fragment, suggests the existence of more than one actin
      binding site in the caldesmon molecule. In this study, the caldesmon-induced
      process of F-actin association was investigated in the presence of skeletal
      myosin subfragment-1, using light-scattering methods, cosedimentation experiment
      and electron microscopic techniques. We show that the actin-caldesmon association
      is partially destabilized in the presence of subfragment-1 and this leads to a
      ternary complex formation. Immunogold labelling of the actin filaments still
      reveals the presence of caldesmon within this structure. This latter result
      strengthens the hypothesis that actin has a site(s) able to bind both caldesmon
      and myosin subfragment-1, as detected by recent NMR observations. This evidence
      is discussed with respect to the regulatory function of caldesmon during smooth
      muscle contraction.

PMID- 2001702
TI  - ATP synthesis in chromatophores driven by artificially induced ion gradients.
AB  - An electrochemical potential difference for protons (delta mu H+) across the
      membrane of bacterial chromatophores was induced by an artificially generated pH
      difference (delta pH) and a K+/valinomycin diffusion potential, delta phi. The
      initial rate of ATP synthesis was measured with a rapid-mixing quenched-flow
      apparatus in the time range between 70 ms and 30 s after the acid-base
      transition. The rate of ATP synthesis depends exponentially on delta pH.
      Increasing diffusion potentials shift the delta pH dependency to lower delta pH
      values. Diffusion potentials were calculated from the Goldman equation. Using
      estimated permeability coefficients, the rate of ATP synthesis depends only on
      the electrochemical potential difference of protons irrespective of the relative
      contribution of delta pH and delta phi.

PMID- 2001703
TI  - Activation and binding volumes of the sarcoplasmic reticulum transport enzyme
      activated by calcium or strontium.
AB  - The effect of pressure on the hydrolysis of dinitrophenyl phosphate (DnpP) and p
      nitrophenyl phosphate (NpP) by the sarcoplasmatic reticulum transport enzyme in
      permeabilized and native closed vesicles activated by calcium or strontium,
      respectively, in aqueous and Me2SO-containing media has been studied. At
      atmospheric pressure, the enzyme in permeabilized vesicles, saturated with
      respect to substrates and activating ions, hydrolyzes DnpP ten times faster than
      NpP; for both substrates, calcium activation exceeds that by strontium only a
      little (20%). In aqueous media the enzyme displays, under all activating
      conditions, an almost identical curvilinear relationship between the logarithm of
      enzyme activity and pressure. The data were analysed on the basis of a simplified
      reaction scheme, in which two unidirectionally proceeding substrate-driven
      pressure-dependent reactions (k2, k4) cyclically transfer high-affinity into low
      affinity binding sites which are assumed to be in equilibrium with either calcium
      or strontium. The fitting procedure yielded two sets of positive activation
      volumes delta V2* = 90-110 ml/mol and delta V4* = 15-25 ml/mol. Substrate
      specificity, as well as the effect of temperature, are exclusively localized in
      the pressure-independent rate constants k'2 and k'4. Considerable different
      pressure/activity relations characterized by a single activation volume of 20
      ml/mol were obtained for the strongly suppressed substrate hydrolysis of native
      closed vesicles. At atmospheric pressure DnpP hydrolysis of open vesicles is
      inhibited by Me2SO, while NpP hydrolysis is considerably activated, irrespective
      of its activation by calcium or strontium. In the presence of 22.5% Me2SO, the
      activation volumes are reduced by 50-70 ml/mol. The rate constants of DnpP and
      NpP hydrolysis are either augmented or reduced by rising Me2SO concentrations,
      depending on the corresponding supporting substrate. Me2SO has only a slight
      effect on the pressure dependence of substrate hydrolysis by native vesicles. The
      small activation volume observed for the activity of native vesicles could be
      assigned on account of the simplified reaction scheme of the slow reaction step
      k4, by which the enzyme is transferred from its low-affinity into its high
      affinity binding state. Volume changes connected with the binding of calcium or
      strontium to the luminal binding site of the enzyme were deduced from the
      observed activation volume and the computed volume change of the slow reaction
      step (delta V4*).

PMID- 2001704
TI  - Deoxyribonucleotide metabolism in hydroxyurea-resistant V79 hamster cells.
AB  - V79 hamster cells were made resistant against hydroxyurea by continuous culture
      at stepwise increasing drug concentrations. Two cell lines were cloned, resistant
      to 0.4 mM (V79/H0.4) and 4 mM (V79/H4) hydroxyurea, with a fivefold and a 20-fold
      increase in soluble ribonucleotide reductase activity. We investigated how the
      increased amount of enzyme affected the in situ activity of ribonucleotide
      reductase and deoxyribonucleotide metabolism, in particular substrate cycles
      between pyrimidine deoxyribonucleosides and their 5'-phosphates. The in situ
      activity of the reductase was only moderately elevated (1.3-fold in V79/H4
      cells). In the fully resistant line, the steady-state level of dATP was increased
      fourfold, and that of dTTP twofold. These nucleotides are negative allosteric
      effectors of the reductase and we propose that the increased pools inhibit the
      enzyme and thereby maintain the in situ activity of the reductase at only a
      slightly increased level. The surplus deoxyribonucleotides was excreted from the
      cells as thymidine and deoxycytidine via substrate cycles. The data support and
      extend our previous model for the regulation of deoxyribonucleotide synthesis via
      the allosteric properties of ribonucleotide reductase and substrate cycles that
      link salvage and degradation of deoxyribonucleotides.

PMID- 2001705
TI  - Structure and expression of the attacin genes in Hyalophora cecropia.
AB  - To study the regulation of the immune genes in insects, we have cloned and
      sequenced the attacin gene locus of the giant silk moth Hyalophora cecropia. The
      locus contains one acidic and one basic attacin gene as well as two pseudogenes,
      which are remnants of basic attacin genes. A small insertion element was found
      within the locus. The two functional attacin genes are transcribed in opposite
      directions and have two introns inserted at homologous positions. A common
      sequence, GGGGATTCCT, is found at nucleotide position -48 in the acidic gene and
      at nucleotide position -58 in the basic gene. Interestingly, this decanucleotide
      is similar to the consensus of the NF-k B-binding site. Expression studies
      revealed that both attacins are strongly induced by phorbol 12-myristate 13
      acetate, lipopolysaccharide and bacteria. However, only the acidic attacin gene
      showed a clear response to injury.

PMID- 2001706
TI  - Kinetics of inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate
      generation in dog-thyroid primary cultured cells stimulated by carbachol.
AB  - The action of carbachol on the generation of inositol trisphosphate and
      tetrakisphosphate isomers was investigated in dog-thyroid primary cultured cells
      radiolabelled with [3H]inositol. The separation of the inositol phosphate isomers
      was performed by reverse-phase high pressure liquid chromatography. The structure
      of inositol phosphates co-eluting with inositol 1,4,5-trisphosphate
      [Ins(1,4,5)P3] and inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P4] standards
      was determined by enzymatic degradation using a purified
      Ins(1,4,5)P3/Ins(1,3,4,5)P4 5-phosphatase. The data indicate that Ins(1,3,4,5)P4
      was the only [3H]inositol phosphate which co-eluted with a [32P]Ins(1,3,4,5)P4
      standard, whereas 80% of the [3H]InsP3 co-eluting with an Ins(1,4,5)P3 standard
      was actually this isomer. In the presence of Li+, carbachol led to rapid
      increases in [3H]Ins(1,4,5)P4. The level of Ins(1,4,5)P3 reached a peak at 200%
      of the control after 5-10 s of stimulation and fell to a plateau that remained
      slightly elevated for 2 min. The level of Ins(1,3,4,5)P4 reached its maximum at
      20s. The level of inositol 1,3,4-trisphosphate [Ins(1,3,4)P3] increased
      continuously for 2 min after the addition of carbachol. Inositol-phosphate
      generation was also investigated under different pharmacological conditions. Li+
      largely increased the level of Ins(1,3,4)P3 but had no effect on Ins(1,4,5)P3 and
      Ins(1,3,4,5)P4. Forskolin, which stimulates dog-thyroid adenylate cyclase and
      cyclic-AMP accumulation, had no effect on the generation of inositol phosphates.
      The absence of extracellular Ca2+ largely decreased the level of Ins(1,3,4,5)P4
      as expected considering the Ca2(+)-calmodulin sensitivity of the Ins(1,4,5)P3 3
      kinase. Staurosporine, an inhibitor of protein kinase C, increased the levels of
      Ins(1,4,5)P3, Ins(1,3,4,5)P4 and Ins(1,3,4)P3. This supports a negative feedback
      control of diacyglycerol on Ins(1,4,5)P3 generation.

PMID- 2001707
TI  - Immunolocalization of cytochromes P-450olf1 and P-450olf2 in rat olfactory
      mucosa.
AB  - Previously, we described two olfactory-specific cytochromes P-450: rat cytochrome
      P-450olf1 (IIG1), identified by cDNA cloning, and bovine cytochrome P-450olf2
      (IIA), identified by peptide microsequencing of a transmembranal polypeptide
      (p52). Here we describe the preparation of polyclonal antisera against peptide
      sequences of these proteins and their use in the immunolocalization of
      cytochromes P-450olf1 and P-450olf2 in rat olfactory mucosa. Immunoreactivities
      related to both enzymes are found in the subepithelial Bowman's glands of
      olfactory mucosa. Practically no immunoreactivity was found in other rat tissues,
      including liver, lung, kidney and respiratory mucosa. In addition, double
      labeling experiments demonstrated that cytochromes P-450olf1 and P-450olf2 are
      present in the same population of Bowman's glands. The olfactory-specific
      localization of cytochromes P-450olf1 and P-450olf2 is consistent with a role for
      these enzymes in the modification or clearance of odorants from the chemosensory
      tissue.

PMID- 2001708
TI  - NMR and circular dichroic studies on the solution conformation of a synthetic
      peptide derived from the calmodulin-binding domain of Bordetella pertussis
      adenylate cyclase.
AB  - The solution conformation of a synthetic peptide of 20 amino acids (P235-254)
      derived from the calmodulin-binding domain of Bordetella pertussis adenylate
      cyclase was studied by proton two-dimensional NMR spectroscopy and circular
      dichroism. Based on the standard techniques we have assigned all the resonances
      in the NMR spectrum to the corresponding protons of the peptide. Analysis of the
      secondary chemical shift distribution and of the nuclear Overhauser effect
      connectivities showed no evidence for a highly populated regular conformation but
      suggested the tendency to form an alpha-helix around the unique Trp residue. The
      propensity for a helical structure is in agreement with the results of circular
      dichroic spectroscopy showing a slight negative band at 222 nm which was
      cancelled by 6 M guanidine hydrochloride. Increasing amounts of 2,2,2
      trifluoroethanol (up to 40%) increase considerably the helical population of the
      peptide as reflected in the circular dichroic spectra. Analysis of the present
      results shows that the free peptide P235-254 has the tendency to form a basic
      amphiphilic helix. The presence of two acid residues, Glu236 and Asp239, on the
      hydrophilic side of the alpha-helix, which is mainly composed by basic residues,
      may explain the lower affinity of this peptide for calmodulin as compared with
      other peptides derived from calmodulin-activated enzymes.

PMID- 2001709
TI  - Structure of the human brain calcium-binding protein calretinin and its
      expression in bacteria.
AB  - Calbindin D28k and calretinin are two closely related intracellular calcium
      binding proteins belonging to the troponin C superfamily. Calbindin is known to
      be involved in the vitamin-D-dependent calcium absorption through intestinal and
      renal epithelia, while the function of neuronal calbindin and calretinin is
      poorly understood. Using antibodies directed against chick intestinal calbindin
      D28k, human calretinin cDNA clones were isolated from brain cDNA libraries. The
      sequence of the calretinin cDNA revealed an open reading frame of 271 codons
      coding for a protein of 31,520 Da, and sharing 58% identical residues with human
      calbindin D28k. Calretinin contains five presumably active and one presumably
      inactive calcium-binding domains. Comparison with the partial sequences available
      for chick and guinea pig calretinins revealed that the protein is highly
      conserved in evolution (evolutionary rate: 0.27 x 10(-9) amino acid-1 year-1).
      The calretinin message was detected in the brain, while absent from heart muscle,
      kidney, liver, lung, spleen, stomach and thyroid gland. Recombinant calretinin
      was expressed in Escherichia coli, and the calcium-binding properties were
      confirmed on both the natural and the recombinant proteins. Part of the human
      gene coding for calretinin was isolated and the region corresponding to the
      promoter and the first exon was sequenced.

PMID- 2001710
TI  - Amino acid 55 plays a central role in tetramerization and function of Escherichia
      coli single-stranded DNA binding protein.
AB  - The histidine at position 55 of the amino acid sequence of the Escherichia coli
      single-stranded DNA binding protein was replaced by tyrosine, glutamic acid,
      lysine, phenylalanine, and isoleucine. The properties of the mutant proteins were
      determined using analytical ultracentrifugation, NMR spectroscopy, gel
      filtration, and fluorimetric detection of their single-stranded DNA binding
      ability. While the phenylalanine and isoleucine substitutions did not change the
      properties of the protein measurably, tyrosine and lysine mutants dissociate into
      subunits and loose some of their binding affinity for poly(dT). For the lysine
      mutant we show by electron microscopy that the protein, although fully
      dissociated and possibly denatured in the free state, binds to poly(dT) as a
      tetramer indistinguishable from the wild-type protein. The process of
      tetramerization as observed via single-stranded DNA binding ability is composed
      of a variety of steps ranging in time from some milliseconds to several hours; it
      probably involves several forms of dissociated and non-native protein.

PMID- 2001711
TI  - Immunology, biosynthesis and in vivo assembly of the branched-chain 2-oxoacid
      dehydrogenase complex from bovine kidney.
AB  - Specific, polyclonal antisera have been raised to the native branched-chain 2
      oxoacid dehydrogenase complex (BCOADC) from bovine kidney and each of its three
      constituent enzymes: E1, the substrate-specific 2-oxoacid dehydrogenase; E2, the
      multimeric dihydrolipoamide acyltransferase 'core' enzyme and E3,
      dihydrolipoamide dehydrogenase. Purified BCOADC, isolated by selective
      poly(ethyleneglycol) precipitation and hydroxyapatite chromatography, contains
      only traces of endogenous E3 as detected by a requirement for this enzyme in
      assaying overall complex activity and by immunoblotting criteria. A weak antibody
      response was elicited by the E1 beta subunit relative to the E2 and E1 alpha
      polypeptides employing either purified E1 or BCOADC as antigens. Anti-BCOADC
      serum showed no cross-reaction with high levels of pig heart E3 indicating the
      absence of antibody directed against this component. However, immunoprecipitates
      of mature BCOADC from detergent extracts of NBL-1 (bovine kidney) or PK-15
      (porcine kidney) cell lines incubated for 3-4 h in the presence of
      [35S]methionine contained an additional 55,000-Mr species which was identified as
      E3 on the basis of immunocompetition studies. Accumulation of newly synthesised
      [35S]methionine-labelled precursors for E2, E1 alpha and E3 was achieved by
      incubation of PK-15 cells for 4 h in the presence of uncouplers of oxidative
      phosphorylation. Pre-E2 exhibited an apparent Mr value of 56,500, pre-E1 alpha,
      49,000 and pre-E3, 57,000 compared to subunit Mr values of 50,000, 46,000 and
      55,000, respectively, for the mature polypeptides. Thus, like the equivalent
      lipoate acyltransferases of the mammalian pyruvate dehydrogenase (PDC) and 2
      oxoglutarate dehydrogenase (OGDC) complexes, pre-E2 of BCOADC characteristically
      contains an extended presequence. In NBL-1 cells, pre-E2 was found to be unstable
      since no cytoplasmic pool of this precursor could be detected; moreover,
      processed E1 alpha was not assembled into intact BCOADC as evidenced by the
      absence of E2 or E3 in immunoprecipitates with anti-(BCOADC) serum after a 45-min
      'chase' period in the absence of uncoupler. Dihydrolipoamide dehydrogenase (E3),
      in its precursor state, was not present in immune complexes with anti-(BCOADC)
      serum, indicating that its co-precipitation with mature complex is by virtue of
      its high affinity for assembled complex in vivo whereas no equivalent interaction
      of pre-E3 with its companion precursors occurs prior to mitochondrial import.

PMID- 2001712
TI  - Molecular parasitology.

PMID- 2001713
TI  - Parasites and molecular biology.

PMID- 2001714
TI  - mRNA processing in the Trypanosomatidae.
AB  - Members of the Trypanosomatidae, which include the African trypanosomes, the
      American trypanosomes and the leishmanias, cause disease in vast proportions in
      man and his livestock and are a major detrimental factor to the social and
      economic well-being of the third world. Current research using the techniques of
      molecular biology has revealed two unusual types of mRNA processing in these
      protozoans; these are the addition of a shared leader sequence to the 5' ends of
      nuclear mRNAs by a mechanism of trans splicing, and the insertion and deletion of
      specific uridine residues in mitochondrial transcripts by RNA editing. The
      presence of these two mRNA processing pathways in the Trypanosomatidae has
      profound consequences for the organization and expression of their genetic
      information.

PMID- 2001715
TI  - Molecular diagnosis of parasites.
AB  - New developments in molecular biology have generated exciting possibilities for
      improved diagnosis of parasitic diseases. Through gene cloning and expression and
      peptide synthesis, defined parasite antigens can be produced in vitro for use in
      serodiagnosis, while nuclear hybridization techniques offer a vastly improved
      approach to identification of parasites in the tissue specimens of infected hosts
      as a means of diagnosis. Furthermore, the advent of the polymerase chain reaction
      technique has made it possible to increase the sensitivity of nuclear
      hybridization techniques, through amplification of target DNA sequences of the
      parasites in test material, by in situ synthesis of these sequences prior to
      hybridization with the diagnostic probe. Finally, through the use of monoclonal
      antibody technology, it is possible to design highly specific and sensitive
      serological assays, as well as assays for parasite antigen detection in tissue
      fluids and in the excreta of infected hosts, as a means of diagnosis.

PMID- 2001716
TI  - Molecular parasitology: progress towards the development of vaccines for malaria,
      filariasis, and schistosomiasis.
AB  - Advances in molecular biology have allowed for the identification of potential
      vaccine candidates against several parasitic diseases. Antigens from various life
      stages of Plasmodium and Schistosoma species and filarial worms have been cloned,
      sequenced and tested as vaccines. Results to date in animal models have been
      promising. Modest levels of protection against experimental human malaria have
      been obtained using both sporozoite and blood-stage antigens. However, a greater
      understanding of the mechanisms which lead to immunity against parasites is
      required before effective vaccines can be developed.

PMID- 2001717
TI  - Malaria vaccine.
AB  - Among infectious diseases caused by protozoa, malaria is still the greatest
      killer of children. Mortality in adults living in endemic areas is significantly
      lower because they frequently acquire partial or complete immunity to the major
      pathogen, Plasmodium falciparum. This natural protection indicates that
      vaccination may be possible, and the first candidate antigens were cloned with
      the use of human immune sera as probes. Genetic and biochemical analysis of the
      parasite proteins revealed that they are polymorphic, and frequently gene
      sequences were discovered which were specific for a particular parasite isolate,
      which eliminated most antigens for purposes of vaccine development. The most
      promising candidate antigens today are the major surface proteins of sporozoites
      and blood stage parasites. However, the immune response against those is not
      sufficient for complete protection, and additional, intensive research is
      necessary to identify new molecules to be included in a vaccine cocktail against
      malaria. The current spread of the disease due to increasing drug resistance of
      parasites and mosquito vectors emphasizes the urgent need for a vaccine.

PMID- 2001718
TI  - Molecular biology and parasites.

PMID- 2001719
TI  - Unsolved and controversial issues in human nutrition. Introduction.

PMID- 2001720
TI  - Human nutrition.

PMID- 2001721
TI  - Effects of exaggerated amino acid and protein supply in man.
AB  - A general update review of the dynamic aspect of protein metabolism is presented.
      The effect of excess protein level on protein metabolism has been the object of a
      limited number of studies in man. From the information available, it appears that
      the primary regulatory pathway for body protein homeostasis is the process of
      amino acid (protein) oxidation.

PMID- 2001723
TI  - Supraphysiological dosages of vitamins and their implications in man.
AB  - Some recent evidence on the benefits and hazards of elevated dosages of vitamins
      is summarized. Special emphasis is given on the safety of vitamins A, D, K1 and
      B6. Furthermore, the possibly beneficial effects of vitamins for athletic
      performance as well as the preventive potential of antioxidative vitamins and of
      carotenoids against cancer are discussed.

PMID- 2001722
TI  - Physiological importance of omega-3/omega-6 polyunsaturated fatty acids in man.
      An overview of still unresolved and controversial questions.
AB  - The 'essentiality' of (omega-6) and (omega-3) fatty acids in mammals is well
      known. Nevertheless, some important points remain unclear concerning their
      implication in physiology. After a short discussion about the definition of
      essential fatty acids deficiency, this brief overview deals with some of these
      points, pointing out some of the unresolved questions. Different subjects are
      approached concerning the (omega-6) and (omega-3) fatty acids metabolism:
      desaturases, eicosanoids, production, as well as some of their metabolic effects
      on cell membranes, intestinal function, glucose and lipid metabolism,
      haemorheology.

PMID- 2001724
TI  - Physiological and nutritional importance of selenium.
AB  - The essential trace element selenium has recently attracted attention because of
      its potentialities in the maintenance of human health. Selenium forms part of the
      active site of the peroxide-destroying enzyme glutathione peroxidase, and it also
      has other functions, for example in biotransformation, detoxification and the
      immune response. Functional and clinical consequences of selenium deficiency
      states have been described, and the selenium requirement, which is influenced by
      the usual selenium exposure, has been discussed. Wide variations have been found
      in selenium status in different parts of the world, and populations or groups of
      patients exposed to marginal deficiency are more numerous than was previously
      thought. Current research activities in the field of human medicine and nutrition
      are devoted to the possibilities of using selenium for the prevention or
      treatment of degenerative or free radical diseases such as neurological
      disorders, inflammatory diseases or cancer. Pharmacological selenium doses are
      also recommended as an adjuvant in some treatments.

PMID- 2001726
TI  - Asiatic cobras: systematics and snakebite.
AB  - The population affinities of the Asiatic cobras of the genus Naja are
      investigated, using multivariate analysis of a range of morphological characters.
      This complex, which was formerly thought to be monospecific, consists of at least
      eight full species. In some cases, species whose bites require different
      antivenoms occur sympatrically. The new understanding of the systematics of the
      Asiatic cobra complex calls for a reappraisal of cobra antivenom use in Asia, and
      for more research into venom composition.

PMID- 2001725
TI  - Inhibitory effects of phenolic compounds on CCl4-induced microsomal lipid
      peroxidation.
AB  - The antiperoxidative effects of 35 phenolic compounds, most of them belonging to
      the flavonoid class, were investigated using CCl4-induced peroxidation of rat
      liver microsomes. This system was rather insensitive to gallic acid, methyl
      gallate and ellagic acid. Nevertheless it was inhibited by flavonoids and
      structure/activity relationships were established. The most potent compounds were
      gardenin D, luteolin, apigenin (flavones), datiscetin, morin, galangin
      (flavonols), eriodictyol (flavanone), amentoflavone (biflavone) and the reference
      compound, (+)-catechin. The natural polymethoxyflavone gardenin D has shown a
      potency comparable to that of (+)-catechin and higher than that of silybin. Thus,
      it may be considered as a new type of natural antioxidant with potential
      therapeutical applications.

PMID- 2001727
TI  - A conformational switch involving the 915 region of Escherichia coli 16 S
      ribosomal RNA.
AB  - A novel alternative conformation, which involves an interaction between the 5'
      terminal and 915 regions (E. coli numbering), is proposed after a screening of
      compiled sequences of small subunit ribosomal RNAs. This conformation contains a
      pseudoknot helix between residues 12-16 and 911-915, and its formation requires
      the partial melting of the 5' terminal helix and the disruption of the 17-19/916
      918 pseudoknot helix of the classical 16 S rRNA secondary structure. The
      alternate pseudoknot helix is proximal to the binding site of streptomycin and
      various mutations in rRNA which confer resistance to streptomycin have been
      located in each strand of the proposed helix. It is suggested that the presence
      of streptomycin favours the shift towards the alternate conformation, thereby
      stabilizing drug binding. Mutations which destabilize the novel pseudoknot helix
      would restrict the response to streptomycin.

PMID- 2001728
TI  - Influence of thyroid hormone on ADP-ribosylation of nuclear proteins in cultured
      GH1 cells.
AB  - We present evidence that T3 can alter the ADP-ribosylation of chromatin
      associated proteins. Nuclei from GH1 cells were incubated with [adenylate-32P]NAD
      and the radioactivity incorporated into histone and non-histone proteins was
      quantitated and analyzed by gel electrophoresis and autoradiography. Incubation
      of GH1 cells for 24 h with T3 lowered by 40-70% the [32P]ADP-ribose incorporated
      into nuclear proteins. However, incubation for 3 h with T3 resulted in a
      stimulation instead of a decrease of in vitro [32P]ADP-ribose incorporation. The
      major ADP-ribosylated component electrophoresed as a 120,000 molecular mass non
      histone protein, and radiolabeled histones were also observed. The same protein
      species were observed for all the experimental groups and T3 affected the extent
      of ADP-ribosylation but did not alter the sedimentation of the [32P]ADP
      ribosylated components excised from chromatin after micrococcal nuclease
      digestion.

PMID- 2001729
TI  - Transcriptional activity of the phosphoenolpyruvate carboxykinase gene decreases
      in regenerating rat liver.
AB  - Rat cytosolic phosphoenolpyruvate carboxykinase (PEPCK) gene expression and
      enzyme activity in liver were studied in rats fasted for 12 hours before and
      after partial hepatectomy, sham operation or no operation. Transcriptional
      activity and mRNA levels decreased in regenerating liver compared to sham
      operated and unoperated controls. In contrast, PEPCK enzyme activity in
      regenerating liver was similar to that in the livers of sham-operated and
      unoperated controls. Since all the animals were fasted the decrease in
      transcription is probably caused by some factor other than insulin, the known
      repressor of PEPCK gene expression.

PMID- 2001730
TI  - Correction of ornithine transcarbamylase (OTC) deficiency in spf-ash mice by
      introduction of rat OTC gene.
AB  - We introduced rat ornithine transcarbamylase (OTC) gene into OTC-deficient spf
      ash mice by mating spf-ash heterozygotes with transgenic mice which carried
      recombinant DNA composed of 1.3 kb of the 5' flanking region of the gene fused
      onto rat OTC cDNA. The liver OTC activity of hemizygous spf-ash mice which
      carried the transgene was about twice that of nontransgenic spf-ash mice, and the
      small intestinal OTC activity was 6 times higher; the values being 12% and 27% of
      the control levels, respectively. The transgenic spf-ash mice showed normal hair
      growth without sparse fur, nearly normalized urinary orotic acid excretion and
      normalized serum citrulline concentration.

PMID- 2001731
TI  - Protection of reaction center II from photodamage by low temperature and
      anaerobiosis in spinach chloroplasts.
AB  - The rate of the irreversible damage to the reaction center II, caused by exposure
      of spinach thylakoids to high light was slowed down by anaerobic conditions and
      by lowering the temperature. The protective mechanisms of these conditions were
      different. In both cases Fmax decreased more slowly than in control
      photoinhibition. A reversible intermediate step was only observed under anaerobic
      conditions. This state was inactive for oxygen evolution and it was characterized
      by an increase of Fo.

PMID- 2001733
TI  - Cloning and sequencing of Lol pI, the major allergenic protein of rye-grass
      pollen.
AB  - We have isolated a full length cDNA clone encoding the major glycoprotein
      allergen Lol pI. The clone was selected using a combination of immunological
      screening of a cDNA expression library and PCR amplification of Lol pI-specific
      transcripts. Lol pI expressed in bacteria as a fusion protein shows recognition
      by specific IgE antibodies present in sera of grass pollen-allergic subjects.
      Northern analysis has shown that the Lol pI transcripts are expressed only in
      pollen of rye-grass. Molecular cloning of Lol pI provides a molecular genetic
      approach to study the structure-function relationship of allergens.

PMID- 2001732
TI  - The nirSTBM region coding for cytochrome cd1-dependent nitrite respiration of
      Pseudomonas stutzeri consists of a cluster of mono-, di-, and tetraheme proteins.
AB  - Genes for respiratory nitrite reduction (denitrification) of Pseudomonas stutzeri
      are clustered within 7 kbp. A 4.6-kbp Hind III-Kpn I fragment carrying nirS, the
      structural gene for cytochrome cd1, was sequenced. An open reading frame
      immediately downstream of nirS codes for a 22.8-kDa protein with four heme c
      binding motifs. Mutagenesis of this gene causes an apparent defect in electron
      donation to cytochrome cd1. Following this ORF are the structural genes for
      cytochrome c552, cytochrome c551, and ORF5 that codes for a 11.9-kDa monoheme
      protein. All cytochromes have a signal sequence for protein export.

PMID- 2001734
TI  - Premature termination of transcription and alternative splicing in the human
      transacylase (E2) gene of the branched-chain alpha-ketoacid dehydrogenase
      complex.
AB  - We have isolated a human genomic clone hgE2-14 containing exons 5, 6, 7 and 8 of
      the branched-chain alpha-ketoacid dehydrogenase E2 transacylase gene. Sequencing
      of exon 8 and its surrounding intronic sequences reveals complete identity with
      the previously reported truncated E2 cDNA (hE2-1) sequence between nucleotides
      938 and 1521. We have identified consensus splice site junctions flanking exon 8
      and also a cryptic 3' splice site 370 bases upstream from the start of exon 8 in
      the gene. In addition, two polyadenylation signals located in the hE2-1 cDNA are
      also present in the intronic sequence downstream of exon 8 which promote
      termination of transcription. The data indicate that shortened human liver E2
      transcripts undergo alternative splicing to yield mRNA of the hE2-1 type.

PMID- 2001735
TI  - Purification of SecE and reconstitution of SecE-dependent protein translocation
      activity.
AB  - SecE was solubilized from SecE-overproducing E. coli cells and purified through
      ion exchange and size exclusion chromatographies. When the solubilized membrane
      containing overproduced amounts of SecY and SecE was fractionated by means of
      size exclusion chromatography, the two proteins were eluted in different
      fractions with slight overlapping. Proteoliposomes active in protein
      translocation were reconstituted from these fractions only when both SecE and
      SecY were present. When reconstitution was carried out with the purified SecE and
      fractions containing SecY but only a small amount of SecE, the resultant
      proteoliposomes exhibited appreciable translocation activity, indicating that
      SecE is essential for protein translocation. The translocation activity of
      proteoliposomes was proportional to the amount of purified SecE used for
      reconstitution. SecE-dependent protein translocation absolutely required ATP and
      SecA.

PMID- 2001736
TI  - The three-dimensional structure of the bifunctional proteinase K/alpha-amylase
      inhibitor from wheat (PK13) at 2.5 A resolution.
AB  - Wheat germ contains an inhibitor for proteinase K, called PK13 (Mr approximately
      19,600) which simultaneously inhibits alpha-amylase. PK13 was crystallized, space
      group P21, a = 43.02 (5) A, b = 65.18 (7) A, c = 32.33 (4) A, beta = 112.79
      degrees (9), X-ray data were collected to 2.5 A resolution, the structure solved
      by molecular replacement on the basis of the atomic coordinates of the homologous
      Erythrina caffra DE-3 inhibitor, and refined with simulated annealing techniques
      with a current R-factor of 21%. The three-dimensional structure of PK13 is
      stabilised by two disulfide bridges and has a central beta-barrel with distorted
      beta-structure. In analogy to related inhibitors, the binding site for proteinase
      K is assumed to be located on the surface of the protein (amino acid residues 66
      67), although the 75-76 peptide bond is cleaved upon binding.

PMID- 2001737
TI  - A high throughput assay for inhibitors of HIV-1 protease. Screening of microbial
      metabolites.
AB  - A novel method for discovery of HIV-1 protease inhibitors in complex biological
      samples has been developed. The assay is based on two specific reagents: a
      recombinant protein constituted by a portion of the HIV-1 Gag polyprotein
      comprising the p17-p24 cleavage site, fused to E. coli beta-galactosidase, and a
      monoclonal antibody which binds the fusion protein in the Gag region. Binding
      occurs only if the fusion protein has not been cleaved by the HIV-1 protease. The
      assay has been adapted for the screening of large numbers of samples in standard
      96-well microtiter plates. Using this method about 12000 microbial fermentation
      broths have been tested and several HIV-1 protease inhibitory activities have
      been detected. One of these has been studied in detail.

PMID- 2001738
TI  - Use of ion exchange chromatography for the study of RecA-DNA interaction.
AB  - In vitro binding of RecA protein to double-stranded DNA (dsDNA) was studied using
      ion-exchange liquid chromatography. The method allowed quantification of both
      free DNA and free protein. The results unambiguously showed a binding
      stoichiometry of 3 base pairs per RecA monomer. The binding exhibited
      cooperativity, and the stoichiometry suggested that RecA does not form complexes
      with two molecules of dsDNA. More than 90% of RecA molecules in the sample were
      active for DNA binding.

PMID- 2001739
TI  - Characterization of cucumber mosaic virus RNA-dependent RNA polymerase.
AB  - Cucumber mosaic virus (CMV) RNA-dependent RNA polymerase (RdRp) was purified form
      CMV-infected tobacco. The purified enzyme is completely dependent on exogenous
      template. The enzyme utilizes a variety of viral RNAs and CMV satellite RNA as
      template for minus-strand synthesis. Cellular RNAs are not used as templates.
      Ribosomal RNA inhibits the viral RNA synthesis by the CMV RdRp.

PMID- 2001740
TI  - Inhibitory effect of calcium-binding protein regucalcin on Ca2(+)-activated DNA
      fragmentation in rat liver nuclei.
AB  - Incubation of isolated rat liver nuclei with ATP, NAD+, and micromolar Ca2+
      concentrations of various metal ions resulted in extensive DNA hydrolysis. Half
      maximal activity occurred with 1.0 microM Ca2+ added, and saturation of the
      process was observed with 10 microM Ca2+. The Ca2+ (10 microM)-activated DNA
      fragmentation was inhibited by the presence of Ca2(+)-binding protein regucalcin
      isolated from rat liver cytosol. The inhibitory effect of regucalcin was complete
      at 0.5 microM. At 25 microM Ca2+ added, such an effect of regucalcin (1.0 microM)
      was not seen. Regucalcin also inhibited Ca2(+)-activated DNA fragmentation in the
      presence of calmodulin (10 and 20 micrograms). The results show that regucalcin
      can inhibit the Ca2(+)-activated DNA fragmentation due to binding the metal,
      suggesting a role in regulation of liver nuclear functions.

PMID- 2001741
TI  - Zinc is required for folding and binding of a single zinc finger to DNA.
AB  - A synthetic peptide corresponding to zinc finger 31 of the Xenopus protein Xfin
      adopts a folded conformation in the presence of zinc. The same peptide in the
      absence of zinc is not folded in a stable tertiary conformation, as determined by
      NMR. Binding experiments have shown that the peptide binds non-specifically to
      DNA only in the presence of zinc. Moreover, competitive DNA binding experiments
      indicate interaction with 3.9 +/- 0.4 base pairs.

PMID- 2001742
TI  - Molecular resolution imaging of polyglucose by scanning tunneling microscopy.
AB  - We have obtained atomic resolution images of poly-alpha-D-glucose by scanning
      tunneling microscopy. The oxygen atoms near the scanning tip were imaged, but the
      carbon and hydrogen atoms were not visible. The measured inter-atomic distances
      are consistent with the molecular structure of poly-alpha-D-glucose deduced from
      chemical and X-ray diffraction studies. The results also demonstrate that is is
      feasible to image surface atomic structures of a relatively thick non-conducting
      specimen, suggesting that the technique may be applied to the study of other
      macromolecules of biological importance.

PMID- 2001743
TI  - Gibberellic acid stimulates acid invertase secretion in pea ovary protoplasts.
AB  - Protoplasts purified from mesocarp of nonpollinated pea (Pisum sativum L.)
      ovaries released acid invertase to the incubation medium. The association of the
      acid invertase with microsomal fractions, and the sensitivity to energy
      metabolism inhibitors and to tunicamycin, indicated the secretory nature of the
      release process. In the presence of GA3 (10 microM), the protoplasts increased
      their invertase secretion at about 60 min, this effect being counteracted by
      tunicamycin but not by cycloheximide. Subcellular fractionation of GA3-treated
      protoplasts showed that higher invertase secretion was the result of a promotion
      of invertase transfer from endoplasmic reticulum (ER) to Golgi apparatus.

PMID- 2001744
TI  - Thionein (apometallothionein) can modulate DNA binding and transcription
      activation by zinc finger containing factor Sp1.
AB  - A number of transcription factors contain so-called zinc finger domains for the
      interaction with their cognate DNA sequence. It has been shown that removal of
      the zinc ions complexed in these zinc fingers abrogates DNA binding and
      transcription activation. Therefore we wanted to test the hypothesis that the
      activity of transcription factors could be regulated by physiological chelators
      of zinc. A prominent candidate for such a chelator is the Cys-rich protein
      thionein (apometallothionein) that is inducible by heavy metal loads, and by
      other environmental stimuli. Here we show with DNA binding and in vitro
      transcription assays that thionein indeed can inactivate the zinc finger
      containing Sp1 in a reversible manner. By contrast, transcription factor Oct-1,
      which binds DNA via a homeo-domain, i.e. a helix-turn-helix motif not involving
      zinc ions, is refractory to thionein action. We propose that modulation of
      intracellular thionein concentration is used for the coordinated regulation of a
      large subset of genes whose transcription depends on zinc finger proteins.

PMID- 2001745
TI  - The transport of glycolic acid by Chlamydomonas reinhardtii.
AB  - Evidence for a transport system for glycolate in Chlamydomonas was obtained.
      [14C]Glycolate was taken up rapidly, reaching an equilibrium in less than 2 s at
      4 degrees C. Glycolate uptake was stimulated by valinomycin and high KCl or high
      KCl alone and inhibited by N-ethylmaleimide. This uptake was not dependent on
      temperature or pH in contrast to uptake of benzoate by diffusion which decreased
      by orders of magnitude with increasing external pH. Based on these data, a
      transporter for glycolate is proposed.

PMID- 2001746
TI  - Saturation kinetics of palmitate uptake in perfused skeletal muscle.
AB  - We investigated the kinetics of palmitate uptake in a physiological skeletal
      muscle preparation by using the isolated perfused rat hindquarter. When plotted
      against the unbound plasma palmitate concentration, palmitate uptake displayed a
      simple Michaelis-Menten relation with a calculated Vmax and Km of 16.3 nmol.min
      1.g-1 and 0.06 mumol.l-1, respectively. These results show that, as in isolated
      cell systems, uptake of free fatty acids in perfused skeletal muscle follows
      saturation kinetics consistent with carrier-mediated membrane transport of free
      fatty acids.

PMID- 2001747
TI  - Studies on the role of the S4 substrate binding site of HIV proteinases.
AB  - Kinetic analysis of the hydrolysis of the peptide H-Val-Ser-Gln-Asn-Tyr*Pro-Ile
      Val-Gln-NH2 and its analogs obtained by varying the length and introducing
      substitutions at the P4 site was carried out with both HIV-1 and HIV-2
      proteinases. Deletion of the terminal Val and Gln had only moderate effect on the
      substrate hydrolysis, while the deletion of the P4. Ser as well as P'3 Val
      greatly reduced the substrate hydrolysis. This is predicted to be due to the loss
      of interactions between main chains of the enzyme and the substrate. Substitution
      of the P4 Ser by amino acids having high frequency of occurrence in beta turns
      resulted in good substrates, while large amino acids were unfavorable in this
      position. The two proteinases acted similarly, except for substrates having Thr,
      Val and Leu substitutions, which were better accommodated in the HIV-2 substrate
      binding pocket.

PMID- 2001748
TI  - Controlled ovarian hyperstimulation and intrauterine insemination for treatment
      of infertility.
AB  - Empirical therapy for subfertility using assisted reproductive technologies
      recently has gained popularity; however, the cost-effectiveness of these
      therapies, compared with an untreated control group, has not been established.
      Similarly, there has been no comparative cost analysis of the utility of
      controlled ovarian hyperstimulation and IUI in the management of the same
      condition. Significant PRs in untreated couples with subfertility mandate the
      design and execution of controlled trials to ascertain the role of controlled
      ovarian hyperstimulation and IUI in infertility therapy. Various disorders of
      subfertility have been treated with controlled ovarian hyperstimulation and IUI.
      The rationale for this therapy is the increase in gamete density at the site of
      fertilization, as with GIFT and IVF when used for management of the same
      problems. The live birth rate per initiated cycle and risk of complications are
      similar to results recently reported for GIFT and IVF. The utility of controlled
      ovarian hyperstimulation and IUI still remains controversial. When the relatively
      low direct and indirect costs of controlled ovarian hyperstimulation and IUI are
      considered, acknowledging the lack of prospective, controlled studies, this
      procedure appears to be at least as cost-effective as GIFT and IVF.

PMID- 2001749
TI  - Probing genomic deoxyribonucleic acid for gene rearrangement in 14 patients with
      androgen insensitivity syndrome.
AB  - Androgen insensitivity appears to involve mutations in the X-linked androgen
      receptor (AR) gene in genetic males. In this study; 14 patients with androgen
      insensitivity syndrome (unrelated patients [n = 6]; related patients [n = 8])
      were studied. Ten patients had complete and 4 had partial insensitivity to
      androgens. Deoxyribonucleic acid samples from controls and study subjects were
      examined with probes specific for the AR gene domains (hAR1, hAR2, hAR3). In one
      subject with complete androgen insensitivity syndrome, a reduction in size of the
      2.4 kilobase band hybridizing to hAR1 was noted. Southern blot analysis of these
      subjects, however, did not detect deletions or gene rearrangement. These results
      suggest that deletions detectable by Southern method are infrequent mutants of
      the AR gene in patients with androgen insensitivity syndrome.

PMID- 2001750
TI  - Combined use of progesterone and human chorionic gonadotropin determinations for
      differential diagnosis of very early pregnancy.
AB  - Progesterone (P) level and daily change in human chorionic gonadotropin (hCG)
      were determined in the serum of 307 patients with suspected ectopic pregnancy
      (EP). Of the viable intrauterine pregnancies (IUP), 99% had P values above 30
      nmol/L, whereas 75% of the EP and 81% of the spontaneous abortions had P values
      less than 30 nmol/L. Among the viable IUP, 95% had normal hCG increases, whereas
      89% of the EP and 99% of the spontaneous abortions had abnormal hCG increases. A
      P value less than 30 nmol/L combined with an abnormal hCG increase had a positive
      predictive value for pathological pregnancy of 1.0. Consequently, in such cases,
      further invasive diagnostic or therapeutic measures can be taken with a low risk
      of jeopardizing a viable IUP.

PMID- 2001751
TI  - Use of a single random serum progesterone value as a diagnostic aid for ectopic
      pregnancy.
AB  - We evaluated the usefulness of serum progesterone (P) determinations in
      differentiating between ectopic pregnancy (EP), normal intrauterine pregnancy
      (IUP), and abnormal IUP. Values were obtained from 233 samples from 54 patients
      with IUP, 100 samples from 26 patients with abnormal IUP, and 125 samples from 46
      patients with EP. Although mean values from all three groups were significantly
      different, we could not detect a single value that readily predicted both the
      presence and absence of EP. Only 2% of patients with EP (excluding those having
      undergone ovulation induction) had a P greater than 20 ng/mL and only 2% of
      patients with IUP had a value less than 10 ng/mL. Thirty-one percent of IUP, 23%
      of abnormal IUP, and 52% of EP had values that fell between 10 and 20 ng/mL,
      which limits the clinical usefulness of this test.

PMID- 2001752
TI  - Detection of premature luteinization with serum progesterone levels at the time
      of the postcoital test.
AB  - Poor cervical mucus (CM) may be caused by a number of factors, including
      premature luteinization, local cervical effects, and inadequate folliculogenesis.
      In an attempt to distinguish between these causes of poor CM, we obtained
      progesterone (P) levels at the time of postcoital tests (PCTs) in infertile women
      during spontaneous or clomiphene citrate (CC)-stimulated cycles. The amount of
      CM, viscosity, ferning, spinnbarkeit, and cellularity were each scored from 0 to
      3 points on the day after detection of the urinary luteinizing hormone surge
      (luteal day 1). The charts of 46 such patients were retrospectively reviewed.
      Eleven control patients with good CM scores (greater than 10) had low P levels
      (less than 2.5 ng/mL). Of the remaining 35 cycles, 19 were marked by low P
      levels, and 16 were accompanied by P levels of greater than 2.5 ng/mL. Overall,
      94.4% of CC-stimulated cycles versus 64.3% of spontaneous cycles had abnormal CM
      scores (less than 9). On the basis of these inappropriately elevated P levels,
      premature luteinization can be cited as the cause of poor mucus quality. In fact,
      premature luteinization may be responsible for some of the purported
      antiestrogenic effects of CC. Therefore, it is appropriate to draw a P level at
      the time of a poor PCT, particularly in cycles stimulated by CC.

PMID- 2001753
TI  - Progesterone production in early pregnancy.
AB  - Before and after elective abortion, progesterone (P) and human chorionic
      gonadotropin (hCG) levels were determined to describe the origin of P and to
      investigate the relationship between levels of hCG and luteal steroidogenesis.
      After abortion, P levels initially fell rapidly, followed by a slower decline.
      The initial fall in P levels and the remaining level of P 3 hours after abortion
      were taken to represent the removal of P that originated from the trophoblast and
      the continuing P contribution by the corpus luteum (CL), respectively. Using this
      analysis, we conclude: (1) P production by the CL is sustained well into the
      second trimester of pregnancy and (2) increasing trophoblastic production of P
      allows the pregnancy progressive independence from the CL.

PMID- 2001755
TI  - Bone mineral density of the lumbar spine in women with endometriosis.
AB  - Young women with endometriosis have reduced cortical and trabecular bone mineral
      density of the wrist compared with age-matched controls. This conclusion was
      based on 41 subjects from one geographical location. The purpose of this study
      was to test this finding in a larger, more geographically diverse population. One
      hundred women with laparoscopically proven endometriosis were enrolled in this
      study for the evaluation of the efficacy of nafarelin, a gonadotropin-releasing
      hormone agonist. Patients were recruited from nine investigators across the
      United States and Canada, and bone mineral density of the lumbar spine was
      obtained at baseline, with 6 Hologic QDR (Hologic Inc., Waltham, MA) and a Lunar
      DPX (Lunar Radiation Corp., Madison, WI) instrument. The age of the women was
      30.3 +/- 5.8 years (mean +/- SD); 91% were white. Bone mineral density of the
      lumbar spine was 1.1 +/- 0.11 g/cm2 (n = 85 Hologic QDR) and 1.2 +/- 0.93 g/cm2
      (n = 15 Lunar DPX). Hologic bone mineral density was 104.8 +/- 11.0 and Lunar
      bone mineral density was 103.4% +/- 7.8% of normal values for age. To conclude,
      in a population based cross-sectional study of patients with endometriosis, we do
      not observe low bone mineral density of the lumbar spine by techniques that
      measure a combination of cortical and trabecular bone.

PMID- 2001754
TI  - The resumption of ovulation and menstruation in a well-nourished population of
      women breastfeeding for an extended period of time.
AB  - We have studied a large group of Australian women breastfeeding for an extended
      period of time to determine the duration of lactational anovulation (n = 89) and
      amenorrhea (n = 101). Salivary progesterone assays were used to determine
      ovulation. These women had a mean of 322 days of anovulation and 289 days
      amenorrhea. Less than 20% had ovulated and less than 25% had menstruated by 6
      months postpartum. The latest ovulation was at 750 days and the latest
      menstruation at 698 days. There was no significant correlation between any
      measure of maternal nutritional status and the duration of anovulation or
      amenorrhea. Neither the time of first supplement introduction to the baby nor the
      amount of supplement given was an accurate predictor of the return of ovulation
      or menstruation. However, our results clearly show that lactational amenorrhea
      can provide good protection against pregnancy in the 1st 6 months postpartum,
      even in well-nourished women who are giving their babies supplemental feeds.

PMID- 2001756
TI  - A satellite system for assisted reproductive technologies: an evaluation.
AB  - The University of North Carolina at Chapel Hill (UNC) Satellite System for
      Assisted Reproductive Technologies (ART) was initiated in 1984, and now serves
      most of North Carolina and parts of two adjoining states. The system was
      established to enhance the care of infertile couples at the community level, to
      assure a sufficiently large volume of patients at UNC Hospitals to support
      appropriate quality control measures, and to allow couples undergoing ART to have
      most of their care in their own community. This paper reports an assessment of
      the outcome of this program. Neither pregnancy rates, nor any other measurable
      result of the program differed between patients managed in the satellites and
      those cared for at UNC Hospitals.

PMID- 2001757
TI  - Ultrasound-guided embryo transfer: a controlled trial.
AB  - Embryo transfer (ET) was performed in 94 patients using transvaginal ultrasound
      guidance. Pregnancy rates were increased over a control group of 246 patients,
      although statistical significance was reached only in the subgroup of single ETs.
      Advantages over the traditional blind technique of ET were observed. Acceptance
      of the procedure by both clinicians and patients was high.

PMID- 2001758
TI  - Experience with peritoneal oocyte and sperm transfer as an outpatient-based
      treatment for infertility.
AB  - Fifty-nine patients underwent 74 peritoneal oocyte and sperm transfer procedures.
      Forty-nine had previously failed treatment with inseminated frozen donor sperm
      and 10 had unexplained infertility. All procedures were carried out under
      ultrasound direction on an outpatient basis without general anesthetic by the
      transabdominal or vaginal route. Eighteen (24%) procedures resulted in pregnancy.
      Of these patients, 16 have delivered live infants (1 set of triplets, 2 twins,
      and 13 singletons) and 2 miscarried. Peritoneal oocyte and sperm transfer offers
      an outpatient-based alternative to gamete intrafallopian transfer (GIFT) for in
      vivo conception. It can also be used in patients scheduled for intrauterine
      insemination where stimulation is excessive because the number of oocytes
      replaced can be limited.

PMID- 2001759
TI  - Detection of human immunodeficiency virus type 1 in semen from seropositive men
      using culture and polymerase chain reaction deoxyribonucleic acid amplification
      techniques.
AB  - We have demonstrated that the polymerase chain reaction is a valid and sensitive
      technique for the detection of human immunodeficiency virus type 1 (HIV-1)
      proviral deoxyribonucleic acid (DNA) in human semen. The combination of
      extraction, polymerase chain reaction, and liquid hybridization techniques used
      in this study was sensitive to a level of detection of one HIV-1 infected cell in
      100,000 (or 3 infected cells/test sample). In a series of matched peripheral
      blood mononuclear cells (PBMC) and semen cells from 25 HIV-1 seropositive
      homosexual men, HIV-1 DNA was detected by polymerase chain reaction in 23 of 25
      PBMC samples and 1 of 25 semen samples. By coculture on mitogen-activated
      peripheral blood leukocyte target cells, 19 of 24 PBMC and 4 of 24 semen samples
      were positive for infectious HIV-1. Of the four culture-positive semen samples,
      three were negative for the proviral form of the virus in the polymerase chain
      reaction assay. These data indicate that HIV-1 infected cells are not as
      prevalent in semen as in the peripheral blood. Furthermore, they indicate that
      the classical polymerase chain reaction approach, which only detects HIV-1
      proviral DNA (infected cells), is not sufficient for clinical screening programs
      whose goal is the detection of HIV-1-infected semen samples. Accurate semen
      analysis by polymerase chain reaction may require enrichment of the infected cell
      population and/or a reverse transcriptase step to enable detection of the
      infectious ribonucleic acid form of the virus.

PMID- 2001760
TI  - The effect of 6 weeks of testosterone treatment on pulsatile luteinizing hormone
      secretion in eugonadal female-to-male transsexuals.
AB  - Polycystic ovary disease generally is associated with elevated androgen levels
      and elevated luteinizing hormone (LH) levels, whereas follicle-stimulating
      hormone (FSH) levels are (sub)normal. To assess the role of androgens on
      gonadotropin secretion, we investigated the effect of 6 weeks of testosterone (T)
      undecanoate, 120 to 160 mg/d orally, on the parameters of the pulsatile secretion
      of LH in a group of six eugonadal female-to-male transsexuals with normal
      menstrual cycles. The treatment suppressed menstrual activity in all patients.
      Serum T and estrone were significantly elevated after treatment with oral T
      undecanoate. The parameters of the pulsatile secretion of LH were not affected by
      androgen administration. Levels of FSH, estradiol, and progesterone also did not
      change significantly.

PMID- 2001761
TI  - Follicular fluid enhances sperm motility and velocity in vitro.
AB  - Forty-three follicular fluids (FFs) obtained during laparoscopy were tested in
      vitro for their effect(s) on sperm motility using gametes obtained by the swim-up
      procedure. Both the proportion of motile sperm and the velocity distribution
      patterns were evaluated as function of time by multiple-exposure photography
      technique. At the various incubation periods considered, all FFs maintained or
      then enhanced sperm motility as compared with the paired control suspension
      incubated with a sperm survival medium. The results of the sperm contact test for
      FFs from women who achieved pregnancy versus FFs from women who remained
      infertile were not significantly different for both parameters measured.
      Comparing these with our previously reported results, we may hypothesize that FF
      released at ovulation into the peritoneal cavity may counteract some sperm
      immobilizing effect of peritoneal fluid, thereby increasing the fertility
      potential of the male gametes.

PMID- 2001762
TI  - The use of an amniotic membrane graft to prevent postoperative adhesions.
AB  - Grafts of trypsin-treated, gamma-irradiated human amniotic membranes were used to
      cover injured uterine horns of nulliparous female rabbits to prevent adhesions.
      In this study, the gradual integration of the membranes into the serosal layer of
      the uterus, together with marked neovascularization, was observed. By the 30th
      postoperative day, the grafts had been completely integrated, with little
      evidence of rejection and no evidence of infection at the graft sites. Of 30
      uterine horns treated with membrane grafts, only 4 (13.4%) showed any adhesion
      formation at or among the graft sites. All of the 24 untreated controls showed
      adhesion formation at the site of injury. Furthermore, whatever adhesions were
      found in membrane-treated horns could be graded as thin and filmy, accounting for
      less than 10% of the surface area of the graft, whereas the controls showed
      dense, thick adhesions covering 50% to 100% of the injured areas. We conclude
      that these specially prepared amniotic membranes are safe and effective in
      dramatically reducing postoperative adhesion formation in this animal model.

PMID- 2001763
TI  - Low human chorionic somatomammotropin fails to predict spontaneous resolution of
      unruptured ectopic pregnancies.
AB  - Early diagnosis of EP allows conservative medical and surgical therapy but also
      commits a proportion of patients whose EP would spontaneously resolve to
      therapeutic intervention. This prospective study examined the feasibility of not
      treating those EPs whose hCS level was low. However, three of eight subjects with
      EP required therapy. Thus, a single hCS alone cannot be used to identify which
      EPs required no therapy.

PMID- 2001764
TI  - Premature menopause because of an inherited deletion in the long arm of the X
      chromosome.
AB  - A family is described in which both a mother and an infertile daughter had
      premature menopause at the ages of 31 and 28 years, respectively. Initially, an
      extensive investigation revealed no apparent cause for their conditions. However,
      when cytogenetic analysis in the daughter was performed, a terminal deletion in
      the long arm of one of the X-chromosomes was found. The karyotype was:
      46,Xdel(X),(q25-qter). Chromosomal investigation in the mother showed an
      identical deletion. The karyotype of the patient's 35-year-old sister is normal.
      She has a normal menstrual cycle and two normal children. The presence of such
      familial cases suggests that chromosomal investigation should be considered in
      young women with oligomenorrhea, especially those whose mothers have experienced
      a premature menopause.

PMID- 2001765
TI  - Limb-body wall complex with complete absence of external genitalia after in vitro
      fertilization.
AB  - The first case of limb-body wall complex (a combination of a body wall defect,
      neural tube defect, and limb abnormalities) after IVF is described. This is the
      third reported patient with this complex anomaly associated with complete absence
      of external genitalia. The possible pathogenic mechanisms are discussed.

PMID- 2001766
TI  - Successful hysteroscopic cannulation and tubal transfer of cryopreserved embryos.
AB  - Clinical trials comparing nonsurgical transfer techniques with laparoscopic
      directed methods are needed to determine the most successful and cost-effective
      approach for gamete and ET. We report the successful nonsurgical transfer of
      frozen-thawed embryos into the fallopian tube after our initial attempt resulting
      in an ongoing IUP. The process is relatively simple, safe, and avoids the risks
      of general anesthesia. Unlike US-guided tubal cannulation, this technique offers
      direct, clear visualization of the tubal ostium, assuring the desired catheter
      placement. As well, hysteroscopic guidance allows an accurate estimate of the
      depth of catheter insertion within the fallopian tube, which may be a critical
      factor in successful tubal deposition of gametes or embryos. Whether prolonged
      carbon dioxide exposure of the tubal microenvironment and/or direct endometrial
      trauma limits the efficacy of this technique remains to be determined. Finally,
      outpatient hysteroscopic directed tubal cannulation holds promise as a
      methodological technique that ultimately assists in the examination of the best
      site for embryo deposition (tubal versus uterine) and/or method of delivery
      (nonsurgical versus surgical).

PMID- 2001767
TI  - Studies on the in vitro spermicidal activity of synthetic magainins.
AB  - Two synthetic magainins A and G are shown to have spermicidal activity.
      Transmission electron microscopic micrographs show that both magainins alter the
      plasma membranes of sperm and that these actions are rapid. Further studies will
      better delineate the contraceptive potential of synthetic magainins.

PMID- 2001768
TI  - Vasectomy and human immunodeficiency virus of mice and men.

PMID- 2001769
TI  - Benefits of intrauterine insemination.

PMID- 2001770
TI  - Complete heart block in an adolescent caused by Lyme disease. A common--and
      reversible--disorder.
AB  - A 20-year-old University of Delaware student developed a vague systemic disorder
      one week after camping in a Maryland state park known to be endemic with the tick
      Ixodes dammini, the vector for Lyme Disease. Light-headedness developed and an
      electrocardiogram revealed complete heart block. Lyme Disease was confirmed by
      the characteristic erythema migrans rash and Lyme serologies.

PMID- 2001771
TI  - HIV seroprevalence survey.

PMID- 2001772
TI  - Aging and spirituality.

PMID- 2001773
TI  - Family Medicine research: major needs.

PMID- 2001775
TI  - The long pull.

PMID- 2001774
TI  - Assessing functional health status.

PMID- 2001776
TI  - Development and validation of the Davis Observation Code.
AB  - Direct observation has demonstrated considerable power in the reliable and valid
      measurement of human behavior. A variety of direct methodologies have been
      applied to physician-patient interactions to answer different types of questions.
      This study describes the development and evaluation of a 20-item direct
      observation scale for physician-patient interactions, the Davis Observation Code
      (DOC). The study compared the rates of occurrence of four key physician behaviors
      measurable by both direct observation and chart audit: disease prevention, health
      education, health promotion, and compliance checking. Forty-nine videotaped
      physician-patient interactions were independently analyzed using the DOC. The
      medical record of each videotaped encounter was also reviewed. Reliability
      determined by inter-rater agreement regarding the presence/absence of each was
      acceptable for both direct observation and chart audit. Rates of occurrence of
      each target behavior differed between the two methods of review; chart audit
      consistently yielded lower rates. Nonparametric correlation analyses yielded phi
      values ranging from .12 to .49, suggesting low concurrent validity. Most of the
      discordance between the results of the videotaped observation and chart audit
      involved underreporting in the chart of observed behavior by the physician.
      Implications of the findings for health care delivery research are discussed.

PMID- 2001777
TI  - Weight reduction in obese hypertensive patients.
AB  - This study tested the feasibility of a low-technology office-based approach to
      weight reduction in obese hypertensive patients. Family practice residents were
      randomly assigned to either an experimental or a control group. Physicians in the
      experimental group were instructed in methods of weight reduction, which they
      then passed on to their patients. Patients of experimental physicians were seen
      monthly, their diets were discussed, and improvements were suggested. The control
      group patients received their usual care. After six months the experimental
      patients had lost significantly more weight than the controls and had
      significantly reduced the number of antihypertensive drugs while maintaining
      blood pressure control. After 12 months there was no significant difference
      between the two groups with respect to weight loss, blood pressure, or number of
      antihypertensive drugs. Experimental and control patients who lost weight had
      visited their physicians more frequently than those who did not and had reduced
      the number of antihypertensive medications they were taking. This educationally
      oriented intervention trial is an example of the type of research that is
      practical to perform in a family practice center and is applicable in family
      physicians' offices.

PMID- 2001778
TI  - The fourth stage of labor: the health of birth mothers and adoptive mothers at
      six-weeks postpartum.
AB  - This study was conducted to determine the frequency of various health problems in
      new adoptive and biological mothers six weeks after they adopted or delivered
      their infants. Participants included 108 married first-time adoptive mothers, 72
      married first-time biological mothers, and 133 controls (married women without
      children), each of whom completed a mailed questionnaire. Compared to controls,
      adoptive and biological mothers reported more fatigue, less readiness to work at
      a job, and less activity with household chores and recreational or social
      functions. In addition, biological mothers complained of more breast and
      genitourinary problems than did adoptive mothers or controls. Apart from their
      fatigue and hesitation to work at a job, adoptive mothers reported relatively
      good health, with the best mental health outcomes and the fewest acute physical
      problems of the three groups. These findings suggest that, for both adoptive and
      birth mothers, some aspects of postpartum recovery may continue up to and beyond
      the sixth postpartum week.

PMID- 2001779
TI  - Conducting family meetings in nursing homes: resident, nurse, and family
      perceptions.
AB  - One facet of the teaching nursing home activities of the Maine-Dartmouth Family
      Practice Residency Program involves requiring residents to schedule a yearly
      family meeting in collaboration with nursing staff for each of the three to six
      nursing home patients for whom they are primarily responsible. During a one-year
      period, meetings were held for 45 of 63 nursing home patients (71%). All
      participants used a simple instrument to evaluate the experience. A general
      outline of the content and process of successful meetings is described. Results
      indicate that families, patients, nurses, and physicians found the meetings
      useful for sharing medical information and providing emotional support. Meetings
      typically reinforced or made only minor refinements in the ongoing plan of care.
      The implementation methods of the project are briefly described so that others
      might consider making yearly family meetings in nursing homes a part of their
      training programs.

PMID- 2001780
TI  - Changes in ambulatory care with patient age: is geriatric care qualitatively
      different?
AB  - Approximately 25,000 recorded visits between primary care physicians and adults
      aged 25 and older in the 1985 National Ambulatory Medical Care Survey were
      analyzed to study the relationship between patient age and selected process
      measures of the physician-patient encounter. Multiple presenting complaints and
      visit diagnoses both rose with age. In spite of this evidence of increased
      complexity of elderly patients, mean visit length for cough, dizziness, diabetes,
      and general medical examinations failed to rise, with longest visits tending to
      be among middle-aged patients. Performance of blood pressure examinations, rectal
      examinations, breast examinations, pelvic examinations, and Papanicolaou (Pap)
      smears on patients presenting for general medical examinations tended to decline
      beyond age 65. These results suggest that individual office visits for older
      patients may be less comprehensive than those for younger adults.

PMID- 2001781
TI  - Using postcards to increase patient provided information on medication use.
AB  - Many elderly persons take medications that their physicians do not know about.
      The reasons include multiple prescribers, errors in prescriber records, and lack
      of patient-to-physician communication on medication use. This study assessed the
      use of mailed cues (postcards) to prompt elderly patients to bring all
      medications to physician office visits. Four family physician offices were
      studied; every other current elderly patient received a postcard reminder several
      days before an appointment. Of those receiving cards, 72% brought in medicines,
      compared to 8% of the controls.

PMID- 2001782
TI  - Goal-oriented medical care.
AB  - The problem-oriented model upon which much of modern medical care is based has
      resulted in tremendous advancements in the diagnosis and treatment of many
      illnesses. Unfortunately, it is less well suited to the management of a number of
      modern health care problems, including chronic incurable illnesses, health
      promotion and disease prevention, and normal life events such as pregnancy, well
      child care, and death and dying. It is not particularly conducive to an
      interdisciplinary team approach and tends to shift control of health away from
      the patient and toward the physician. Since when using this approach the enemies
      are disease and death, defeat is inevitable. Proposed here is a goal-oriented
      approach that is well suited to a greater variety of health care issues, is more
      compatible with a team approach, and places a greater emphasis on physician
      patient collaboration. Each individual is encouraged to achieve the highest
      possible level of health as defined by that individual. Characterized by a
      greater emphasis on individual strengths and resources, this approach represents
      a more positive approach to health care. The enemy, not disease or death but
      inhumanity, can almost always be averted.

PMID- 2001783
TI  - The house call in residency training and its relationship to future practice.
AB  - The aging of the population makes education in geriatrics vital to family
      practice residents, including training in house calls. This study examined the
      relationship of house call training in residency with current house call
      practices of recent graduates of family practice residencies. A questionnaire
      mailed to a random national sample of 301 family physicians who completed
      residency training between 1981 and 1986 obtained a 66% response rate with three
      mailings. House calls were not required in the curriculum for 80% of respondents,
      30% never did house calls in residency, and 55% recognized they were not well
      trained in house calls. Graduates of programs in which faculty made house calls
      and those in which residents made house calls on a longitudinal basis were
      significantly more likely to offer house calls in their practices. This suggests
      that resident education can offer positive experiences in house call training to
      encourage future physicians to include house calls in their practices.

PMID- 2001784
TI  - Chlamydia trachomatis infections in children evaluated for sexual abuse.
AB  - The purpose of this study was to elucidate the conditions under which children
      evaluated for sexual abuse should be tested for Chlamydia trachomatis. Children
      were seen in an outpatient sexual abuse clinic over a nine-month period. Eight
      patients, ranging from 1.5 to 14.5 years of age, had positive C. trachomatis
      cultures. The records of these patients were examined for historical information
      and physical findings suggestive of rectal or vaginal penetration. Neither
      historical information of abuse nor physical findings were helpful in predicting
      the C. trachomatis infections. These results suggest that all children being
      evaluated for sexual abuse should be cultured for C. trachomatis.

PMID- 2001785
TI  - NASA--a new course? A biologist's view of the Augustine report.

PMID- 2001786
TI  - Perisinusoidal stellate cells of the liver: important roles in retinol metabolism
      and fibrosis.
AB  - In mammals, liver perisinusoidal stellate cells play an important role as a main
      store of body retinol (vitamin A). This fat-soluble vitamin is essential for
      vision, and regulates differentiation and growth of many cell types during
      embryonal development as well as in adult tissues. Thus, many cell types require
      a continuous supply of retinol. The storage of retinol (as retinyl esters) in
      stellate cells ascertains ample access of retinol to such cells also during
      periods with a low dietary intake. In lower vertebrates such as fish, vitamin A
      storing stellate cells are found not only in the hepatic lobule, but also in the
      connective tissues of organs like intestine, kidney, ovaries, testes, and gills.
      Extrahepatic vitamin A-storing stellate cells are found in higher vertebrates
      when excessive doses of vitamin A are administered. It is not clear at present
      whether these cells also play a role in retinol metabolism under normal
      conditions. Stellate cells proliferate in a fibrotic liver, and they have been
      found to synthesize connective tissue compounds such as collagen. It was recently
      demonstrated that stellate cells are the principal cellular source of collagen
      and other extracellular substances in normal as well as fibrotic livers.
      Therefore, stellate cells, which seem to be a specialized type of pericyte, have
      a central role in the pathological changes observed during the development of
      liver fibrosis.

PMID- 2001787
TI  - Advances in Alzheimer's disease.
AB  - The problem of the etiology of Alzheimer's disease has not been solved. But in
      the past several years there have been significant extensions of our knowledge of
      the disease and advances in determining the molecular changes underlying the
      disorder. There is now convincing evidence that the dementia per se is caused by
      loss of neurons and synapses, particularly in neocortex and hippocampus. The
      molecular aspects of amyloid and its precursor protein have been defined. The
      nature of intracellular changes leading to accumulation of the paired helical
      filament is beginning to be understood. For the first time, putative risk factors
      can be described in terms of pathogenetic mechanisms. Thus, it may become
      possible in the not-too-distant future to discover interventions that will slow
      the progress of this devastating disease.

PMID- 2001788
TI  - Cell culture models of differentiation.
AB  - It is now possible to culture cells from most organs of the body under conditions
      in which they continue to express at least some of their differentiated traits,
      and to model some of the differentiation processes that occur during embryonic
      and adult life. How much can these cultures tell us about the acquisition and
      maintenance of the differentiated state? To answer this question I shall outline
      the features of several cell culture models, dividing them into categories
      according to whether they mimic differentiation during development,
      differentiation of adult stem cell progeny, or the transition from one
      differentiated phenotype to another. In spite of the diversity of cell types
      under consideration, it is possible to detect some common themes: the stability
      of the differentiated state; the relationship between proliferation and
      differentiation; the relative importance of intrinsic cellular programming and
      environmental regulation; and possible mechanisms for transcriptional control of
      the genes that are activated during differentiation. In recent years cell culture
      models have yielded a great deal of information about differentiation and the way
      is now clear for even more exciting discoveries.

PMID- 2001789
TI  - Saposin proteins: structure, function, and role in human lysosomal storage
      disorders.
AB  - Saposins are sphingolipid activator proteins, four of which are derived from a
      single precursor, prosaposin, by proteolytic processing. These small heat-stable
      glycoproteins (12-14 kDa) are required for the lysosomal hydrolysis of a variety
      of sphingolipids. Characterization of these four activator proteins, two of which
      were recently discovered, and their importance in human health and disease are
      reviewed in this article.

PMID- 2001790
TI  - How are the regulators regulated?
AB  - The cell-type-specific expression of many genes is determined at the level of
      transcription. Transcription factors, acting at promoter and enhancer elements,
      are involved in the control of this process. To understand the basis of this
      regulation it has become important to analyze the control of transcription
      factors themselves. A variety of transcriptional, translational, and
      posttranslational mechanisms have been described, and are discussed in this
      review article.

PMID- 2001791
TI  - Cross-talk between receptor-regulated phospholipase D and phospholipase C in
      brain.
AB  - Because receptors, G proteins, and phospholipases all exist within a membrane
      lipid environment, it is not unreasonable to assume that an enzyme capable of
      changing the lipid environment can affect the coupling relationship among these
      signal transducing components. Our previous study showed that a muscarinic
      acetylcholine receptor regulates phosphatidylcholine phospholipase D via a G
      protein in brain. We demonstrate here that phosphatidylinositol phospholipase C
      and phosphatidylcholine phospholipase D are simultaneously activated within 15 s
      by muscarine in the presence of 1 microM GTP gamma S. More important, inhibition
      of phospholipase D by zinc attenuated carbamylcholine-induced activation of
      phospholipase C by 30%. Our additional evidence strongly indicates that the
      receptor-regulated phospholipase D plays an important modulatory role in agonist
      stimulated phosphatidylinositol breakdown. This modulatory effect may be achieved
      by changing the membrane microenvironment in which phospholipase C and
      phosphoinositol lipids reside, consequently amplifying the inositol phospholipid
      signaling process. Our results lead us to postulate that the potential
      interaction between two different signaling pathways may provide a cell with
      intracellular coordination and enable the cell to achieve functional responses.

PMID- 2001792
TI  - Induction of HL-60 cell differentiation by water-soluble and nitrogen-containing
      conjugates of retinoic acid and retinol.
AB  - Retinoids induce the promyelocytic cell line, HL-60, to differentiate along the
      granulocytic pathway in vitro. A number of water-soluble and nitrogen-containing
      retinoids were synthesized in our laboratory [retinoyl-glucose (RAGL), retinyl
      glucose (ROGL), retinoyl-adenosine (RADS), retinoyl-adenine (RAD), retinoyl-beta
      glucuronide (beta RAG), and retinoyl-alpha-glucuronide (alpha RAG)]. These
      retinoids (10(-5) to 10(-8) M), as well as retinoic acid (RA) and retinol (ROL),
      were tested for their ability to induce the differentiation of HL-60 cells in
      vitro and to affect cell growth and viability during a 24- to 72-h incubation
      period. Differentiation was assessed by measuring the percentage of cells
      expressing the Mac-1 antigen on their cell surfaces. RA and the conjugates of RA
      were all quite active in inducing HL-60 cell differentiation, whereas ROL and
      ROGL had much less activity at equimolar concentrations. beta RAG, alpha RAG,
      RADS, and RAD were less toxic, whereas the glucose conjugates of retinol and
      retinoic acid (ROGL and RAGL) were both considerably more toxic than either RA or
      ROL at equimolar concentrations. All retinoids affected cell growth in a dose
      dependent fashion. At 24 h, free RA or ROL was not detected in the cells after
      incubation with any of the retinoid conjugates.

PMID- 2001793
TI  - Fructose administration stimulates glucose phosphorylation in the livers of
      anesthetized rats.
AB  - A method allowing one to measure the rate of glucose phosphorylation in the
      livers of anesthetized rats is described. Upon injection of [2-3H]glucose into
      the portal vein, about 90% of the radioactivity remained in the liver for
      approximately 30 s. The proportion of radioactivity accounted for by tritiated
      water increased linearly at a rate of about 5%/min in control animals. Fructose
      injected into the penile vein stimulated this rate up to 2.2- and 2.7-fold in fed
      and overnight starved rats respectively, a maximal effect being observed at a
      dose of 50 mg/kg under both conditions. Fructose was also active when
      administered by intragastric infusion. The ketose caused increases in the
      concentration of fructose 1-phosphate, which reached values known to relieve the
      inhibition exerted on glucokinase by its regulatory protein.

PMID- 2001794
TI  - Molecular cloning and characterization of two voltage-gated K+ channel cDNAs from
      human ventricle.
AB  - K+ channels represent the most complex class of voltage-gated ion channels from
      both functional and structural standpoints. In the heart these channels are
      responsible for the rapid repolarizing phases of the action potential and are the
      targets of several antiarrhythmic drugs. Full-length cDNA clones were isolated
      from human ventricular libraries that encode two voltage-gated K+ channels. These
      two cDNAs, designated HK1 and HK2, encode proteins of 653 and 605 amino acids,
      respectively. HK1 is the human equivalent (98% identity) of an inactivating K+
      channel previously described in rat heart (RHK1) whereas the HK2 channel is 86%
      identical to a cloned rat brain K+ channel (Kv1). The only amino acid sequence
      identity (72%) between HK1 and HK2 is within the central region containing the
      membrane spanning domains. Northern blot analysis of human mRNA indicated that
      HK1 is slightly more abundant in ventricle than atrium whereas HK2 is much more
      abundant in atrium relative to ventricle. Both channel transcripts are present in
      ventricle at levels equivalent to voltage-gated Na+ channels. Analysis of the
      gene encoding HK1 suggests the coding sequence is intronless and is represented
      once in the human genome.

PMID- 2001796
TI  - Federation of American Societies for Experimental Biology. 75th Annual Meeting.
      Atlanta, Georgia, April 21-25, 1991. Part II. Abstracts.

PMID- 2001795
TI  - Unique fatty acid composition of normal cartilage: discovery of high levels of n
      9 eicosatrienoic acid and low levels of n-6 polyunsaturated fatty acids.
AB  - We report here the finding that normal, young cartilages, in distinction from all
      other tissues examined, have unusually high levels of n-9 eicosatrienoic (20:3
      cis-delta 5,8,11) acid and low levels of n-6 polyunsaturated fatty acids (n-6
      PUFA). This pattern is identical to that found in tissues of animals subjected to
      prolonged depletion of nutritionally essential n-6 polyunsaturated fatty acids
      (EFA). This apparent deficiency is consistently observed in cartilage of all
      species so far studied (young chicken, fetal calf, newborn pig, rabbit, and
      human), even though levels of n-6 PUFA in blood and all other tissues is normal.
      The n-9 20:3 acid is particularly abundant in phosphatidylethanolamine,
      phosphatidylinositol, and the free fatty acid fractions from the young cartilage.
      Several factors appear to contribute to the reduction in n-6 PUFA and the
      appearance of high levels of the n-9 20:3 acid in cartilage: 1) limited access to
      nutritional sources of EFA due to the impermeability and avascularity of
      cartilage, 2) rapid metabolism of n-6 PUFA to prostanoids by chondrocytes, and 3)
      a unique fatty acid metabolism by cartilage. Evidence is presented that each of
      these factors contributes. Previously, EFA deficiency has been shown to greatly
      suppress the inflammatory response of leukocytes and rejection of tissues
      transplanted into allogeneic recipients. Because eicosanoids, which are derived
      from EFA, have been implicated in the inflammatory responses associated with
      arthritic disease, reduction of n-6 PUFA and accumulation of the n-9 20:3 acid in
      cartilage may be important for maintaining normal cartilage structure.

PMID- 2001797
TI  - Federation of American Societies for Experimental Biology, 75th annual meeting.
      Atlanta, Georgia, April 21-25, 1991. Part III. Abstracts.

PMID- 2001798
TI  - Human anal motility while fasting, after feeding, and during sleep.
AB  - The aim of this study was to determine whether the human anal sphincter responds
      dynamically to changing physiological states. In 19 healthy human subjects,
      intraluminal anal canal pressure was measured with a 5-cm perfused sleeve sensor
      during the day while fasting (3 hours) and after feeding (3 hours) and at night
      during sleep (8 hours). Daytime mean anal canal pressures (+/- SEM) while fasting
      (50 +/- 3 mm Hg) were similar to those after feeding (49 +/- 3 mm Hg) and to
      those at night during sleep (49 +/- 3 mm Hg). Marked minute-to-minute variations
      in mean pressure occurred in all three periods, however, as did large phasic
      increases and decreases in pressure (greater than 20 mm Hg) and small phasic
      changes in pressure less than 20 mm Hg (anal slow waves). The minute-to-minute
      variations in mean pressure were greater during the awake fed state (4 +/- 1 mm
      Hg/min) than at night during sleep (2 +/- 1 mm Hg/min; P less than 0.03), as were
      the number of large phasic waves per minute (increases in pressure: awake, fed =
      0.5 +/- 1 waves/min, night = 0.3 +/- 0.1 waves/min, P less than 0.05; decreases
      in pressure: awake, fed = 0.4 +/- 0.1 waves/min, night = 0.2 +/- 0.1 waves/min, P
      less than 0.05). Anal small waves had a similar frequency of about 17 waves/min
      in all three states. In conclusion, the anal sphincter maintains a continuous
      pressure barrier to rectal outflow both during the day and at night during sleep.
      However, marked minute-to-minute variations in mean pressure and large phasic
      increases and decreases in pressure do occur. Both are fewer at night during
      sleep.

PMID- 2001799
TI  - Differential effect of streptozotocin-induced diabetes on the innervation of the
      ileum and distal colon.
AB  - The effect of short-term and long-term streptozotocin-induced diabetes on the
      pattern of distribution and tissue content of adrenergic and peptidergic nerves
      in ileum and distal (descending) colon of the rat was examined using
      immunohistochemical, biochemical, and immunochemical techniques. The effect of
      short-term streptozotocin-induced diabetes on the level of noradrenaline compared
      with weight-restricted (starved) and untreated controls in the celiac (celiac
      superior mesenteric ganglia complex) and inferior mesenteric ganglia, which
      supply the two regions of the intestine, was also compared. The pattern of change
      in the distribution of dopamine-beta-hydroxylase-, substance P-, calcitonin gene
      related peptide-, and vasoactive intestinal polypeptide-like immunoreactive nerve
      fibres that was observed in the ileum from diabetic rats was not evident in the
      myenteric plexus of distal colon. In contrast to the ileum, there was no evidence
      of degenerative change in any of the nerve types investigated in the myenteric
      plexus of the distal colon. The level of vasoactive intestinal polypeptide in the
      diabetic rat ileum was significantly increased, whereas the level of
      noradrenaline was reduced; no such changes were observed in the distal colon. The
      tissue content of noradrenaline in the celiac ganglion, which projects to the
      ileum, was increased at 8-week diabetes compared with both weight-restricted and
      untreated controls, whereas the diabetic state had no effect on the levels of
      noradrenaline of the inferior mesenteric ganglion, which projects to the distal
      colon. It is concluded that there is a differential effect of streptozotocin
      diabetes on different regions of the rat intestine. The adrenergic and
      peptidergic innervation of the distal colon were changed little compared with
      ileum. This may be explainable in terms of the different functional roles of
      these two regions of the intestine and/or by the difference in origin of the
      sympathetic nerves supplying the two regions of the intestine.

PMID- 2001800
TI  - Adenocarcinomas of the colon and rectum in persons under 40 years old. A
      population-based study.
AB  - Data collected by nine population-based tumor registries participating in the
      Surveillance, Epidemiology, and End Results Program of the National Cancer
      Institute were analyzed to characterize the epidemiology of noncarcinoid
      adenocarcinomas of the colon and rectum in young adults. Tumors diagnosed in
      persons under 40 years old between 1973 and 1984 (n = 1736) were compared with
      those in persons 40 years and older (n = 106,760). This first large U.S.
      population-based study of colorectal adenocarcinomas in the young shows a higher
      incidence in blacks than whites and later detection in black males. It also shows
      a higher proportion of tumors of mucinous and signet ring histological type than
      in older age groups. Among the younger group, the average annual age-adjusted
      incidence rate was 34% higher in black males than in white males (12.6 vs. 9.4
      per million persons) and 46% higher in black females than in white females (13.0
      vs 8.9 per million persons). The proportion of tumors that were right-sided
      varied by age: 0-29 years, 30%; 30-39 years, 26%; 40-49 years, 22%; 50-59 years,
      21%; 60-69 years, 24%; 70-79 years, 30%; and 80+ years, 35%. Males under age 40
      were less likely to present with localized disease (whites, 27%; blacks, 21%)
      than were those aged 40 and older (whites, 39%; blacks, 36%). The proportion of
      tumors classified as mucinous decreased with age, from 28% among those aged 0-19
      years to 5% among those 40 years and older. A similar trend was observed for
      signet ring tumors. Although this latter type accounted for 10% of large-bowel
      tumors among subjects aged 0-19 years, this proportion decreased with age to 0.2%
      in those 40 years and older.

PMID- 2001801
TI  - Effect of glucagon on hepatic energy charge and arterial ketone body ratio in
      normal rabbits.
AB  - Glucagon has been regarded as a hepatotrophic factor, although it is also known
      to stimulate energy-consuming reactions in the liver, such as gluconeogenesis and
      ureogenesis. To clarify the effect of glucagon on the hepatic energy metabolism,
      the changes in arterial ketone body ratio, which reflects the hepatic
      mitochondrial redox state [( NAD+]/[NADH]), as well as those in energy charge and
      mitochondrial oxidative phosphorylation of the liver after IV glucagon injection
      were studied in normal rabbits. Arterial ketone body ratio decreased
      significantly from 1.04 +/- 0.08 to 0.61 +/- 0.11 (mean +/- SEM; P less than
      0.01) within 30 minutes after glucagon injection. Hepatic energy charge also
      decreased from 0.883 +/- 0.014 to 0.789 +/- 0.014 (P less than 0.01) at 30
      minutes, whereas mitochondrial phosphorylation rate inversely increased from 38.4
      +/- 9.5 to 87.3 +/- 9.7 (nanomoles adenosine triphosphate per milligram
      mitochondrial protein per minute; P less than 0.01) at 30 minutes. Arterial
      ketone body ratio and energy charge were subsequently restored to the initial
      values at 60 minutes and 2 hours, respectively. The present study suggests that
      glucagon causes an increase in energy expenditure in the liver that results in a
      transient decrease in hepatic energy charge accompanied by a decrease in arterial
      ketone body ratio.

PMID- 2001802
TI  - Hepatic metabolism of cholesterol in Crohn's disease. Effect of partial resection
      of ileum.
AB  - To study cholesterol metabolism in Crohn's disease and especially the effect of
      ileum resection, liver biopsy specimens were obtained from patients undergoing
      partial ileal resection because of Crohn's disease (n = 17) and patients with
      Crohn's colitis undergoing colectomy (n = 3). Gallstone-free patients (n = 16)
      undergoing cholecystectomy because of adenomyomas or polyps of the gallbladder
      served as controls. The mean levels of cholesterol 7 alpha-hydroxylase activity
      and 3-hydroxy-3-methylglutaryl coenzyme A reductase activity, rate-determining
      enzymes in bile acid, and cholesterol synthesis, respectively, were twofold to
      threefold higher in the ileum-resected patients than in the controls. Significant
      positive correlations were obtained between length of resected ileum and
      cholesterol 7 alpha-hydroxylase activity. Provided patients who had received
      total parenteral nutrition preoperatively were excluded from analysis, a
      significant correlation was also observed between length of resected ileum and 3
      hydroxy-3-methylglutaryl coenzyme A reductase activity. Significant positive
      correlations were also obtained between length of resected ileum and serum levels
      of 7 alpha-hydroxycholesterol (a marker for bile acid biosynthesis) and
      lathosterol (a marker for cholesterol synthesis). The plasma levels of total and
      low-density lipoprotein cholesterol were negatively correlated to the length of
      resected ileum. The expression of hepatic low-density lipoprotein-receptor
      binding activity was determined in five of the patients and in three of the
      controls. A significant positive correlation was observed between 3-hydroxy-3
      methylglutaryl coenzyme A reductase activity and low-density lipoprotein-receptor
      binding activity. The results show that malabsorption of bile acids leads to
      parallel stimulation of cholesterol synthesis, cholesterol degradation, and low
      density lipoprotein-receptor expression in human liver. The resulting effect in
      the present patients was a significant reduction in low-density lipoprotein
      cholesterol.

PMID- 2001803
TI  - Loss of zonal heterogeneity and cell polarity in rat liver with respect to bile
      acid secretion after bile drainage.
AB  - Functional liver heterogeneity depends on the current perihepatic environment.
      The effect of chronic bile drainage on hepatic secretion of bile acids in
      periportal and pericentral rat liver cells was studied. After 4 days of biliary
      drainage, rat livers were perfused in vitro in either forward (through the portal
      vein) or backward direction (through the vena cava) in single-pass arrangement
      with taurodeoxycholate (32 nmol.min-1.g liver-1). Tritium-labeled
      taurodeoxycholate (0.5 muCi) was injected as a pulse to determine uptake,
      biotransformation, and hepatic secretion. During bile drainage, bile flow fell
      from 1.8 microL.min-1.g liver-1 to approximately 0.6 microL.min-1.g liver-1. Bile
      acid secretion rate dropped from initially 50 nmol.min-1.g liver-1 to
      approximately 5 nmol.min-1.g liver-1 within 24 hours and remained at this level
      for the next 3 days. After bile drainage, liver histology was well preserved and
      was indistinguishable from controls. During liver perfusion of controls in both
      directions, bile flow exceeded 1 microL.min-1.g liver-1, whereas bile-drained
      animals demonstrated a bile flow between 0.4 and 0.6 microL.min-1.g liver-1. In
      contrast to controls, the drained-animal liver did not excrete label exclusively
      in bile but simultaneously excreted about one third back to the perfusate medium
      (regurgitation). Biliary bile acid recovery within the first 10 minutes after 3H
      taurodeoxycholate bolus injection was 90% (of label taken up) in forward-perfused
      controls but only 40% in forward-perfused drained animals. Backward-perfused
      control and drained animals. Backward-perfused control and drained animals
      excreted about 20% in this time interval and did not differ significantly. T50,
      the time to excrete 50% of label taken up in bile or both bile and effluent,
      increased from 4.3 +/- 0.36 minutes (SD) in forward-perfused controls to 13.2 +/-
      2.28 minutes in forward-perfused, drained animals. T50 of backward-perfused
      controls and backward-perfused drained animals did not differ significantly (17.8
      +/- 1.75 minutes vs. 21.0 +/- 3.95 minutes). In conclusion, chronic bile drainage
      reduces liver heterogeneity with respect to velocity of bile acid excretion and
      cell polarity is lost with respect to hepatocellular translocation of bile acids.

PMID- 2001804
TI  - Levels of Cu-Zn and Mn superoxide dismutases in rat liver during development.
AB  - Superoxide dismutase is the main scavenger of superoxide radicals in the
      mammalian body. The liver has high levels of two types of superoxide dismutase
      enzymes, cytosolic Cu-Zn and mitochondrial Mn enzymes. The aim of the present
      study was to investigate the content of two distinct superoxide dismutases in
      liver during the perinatal transition from a hypoxic to a hyperoxic environment.
      Both isozymes were purified to homogeneity and used as immunogens in rabbits.
      Antisera raised were found to recognize only polypeptides of molecular weight
      16,900 or 23,400, which correspond to Cu-Zn and Mn superoxide dismutases,
      respectively. It was found that the level of Cu-Zn superoxide dismutase enzymatic
      activity and protein as assessed by immunoquantitation increased 10-fold during
      the postnatal period, reaching adult levels by 3 weeks. In contrast, the amount
      of Mn superoxide dismutase content increased only twofold to adult levels during
      the first week of life. Neither of the superoxide dismutases showed an alteration
      in specific activity or apparent molecular weight in rat livers during ontogeny.
      These results show that the levels of two intracellular superoxide dismutases are
      differentially elevated during the perinatal period. It is suggested that each
      dismutase plays a different physiological role for superoxide scavenging in liver
      as a function of the hypoxic/hyperoxic environment at birth.

PMID- 2001805
TI  - Systemic and renal production of thromboxane A2 and prostacyclin in decompensated
      liver disease and hepatorenal syndrome.
AB  - To assess the role of altered renal and systemic production of thromboxane A2 and
      prostacyclin in the hepatorenal syndrome, urinary excretion of their major renal
      and extrarenal metabolites was measured in patients with compensated and
      decompensated liver disease, chronic renal failure, and hepatorenal syndrome.
      Urinary excretion rates of all prostanoids (renal and extrarenal) were increased
      in subjects with liver disease compared with normal controls. Moreover, they were
      considerably higher in subjects with severe hepatic decompensation but good renal
      function compared with those with hepatorenal syndrome. In contrast, the
      excretion rate of all metabolites was reduced in patients with chronic renal
      failure. The excretion rate of all metabolites was markedly elevated during the
      early stages of hepatorenal syndrome and decreased in parallel with creatinine
      clearance. When corrected for creatinine clearance, there was a strong
      correlation between prostanoid excretion and serum bilirubin in subjects with
      liver disease; there was no difference, however, in the excretion of renal and
      extrarenal prostanoids between hepatorenal syndrome and severe hepatic
      decompensation. It is concluded that hepatic decompensation is associated with a
      progressive increase in prostanoid excretion but that changes in production of
      prostacyclin or thromboxane A2 are unlikely to be major factors in the
      pathogenesis of the hepatorenal syndrome.

PMID- 2001806
TI  - Portacaval shunt versus endoscopic sclerotherapy in the elective treatment of
      variceal hemorrhage.
AB  - Eighty-two consecutive Child-Campbell class A and B cirrhotic patients were
      included in a prospective controlled trial to assess the efficacy and safety of
      portacaval anastomosis vs. endoscopic sclerotherapy as elective treatment of
      variceal hemorrhage. Forty-one patients were randomized to portacaval anastomosis
      and 41 to sclerotherapy. After excluding dropouts, 34 patients were treated with
      portacaval anastomosis and 35 with sclerotherapy. The incidence of variceal
      rebleeding during follow-up (mean +/- SD, 20.6 +/- 14.2 months) was significantly
      higher in the sclerotherapy than in the portacaval groups, either considering the
      overall treated group or only patients completing sclerotherapy (40% and 25% vs.
      2.9%; P = 0.0002 and P = 0.01, respectively). The 2-year probability of suffering
      from at least one episode of hepatic encephalopathy was significantly higher in
      patients submitted to portacaval anastomosis than in those treated with
      endoscopic sclerotherapy (40% vs. 12%; P = 0.04). However, disabling
      encephalopathy only appeared in 3 of 34 patients who underwent surgery (8.8%).
      Early and long-term mortality did not differ between the therapeutic groups; 2
      year survival rates were 83% for portacaval anastomosis and 79% for
      sclerotherapy. It is concluded that portacaval anastomosis is more effective than
      endoscopic sclerotherapy in preventing variceal rebleeding in spite of the
      greater incidence of hepatic encephalopathy. The role of portacaval anastomosis
      in the elective treatment of variceal rebleeding should be reassessed.

PMID- 2001807
TI  - Fulminant hepatitis B: induction by hepatitis B virus mutants defective in the
      precore region and incapable of encoding e antigen.
AB  - Clones of hepatitis B virus were propagated from 10 cases of fulminant hepatitis
      B after amplification by polymerase chain reaction and their nucleotide sequences
      of the precore region were determined. All 113 clones from 9 cases had a point
      mutation from guanine to adenine at nucleotide 83 in the precore region, which
      converted codon 28 for tryptophan (TGG) to a stop codon (TAG) and prohibited the
      synthesis and secretion of hepatitis B e antigen. Precore-region defects were not
      detected in any of 23 clones from the remaining 1 case. By contrast, precore
      region defects were not found in any of 180 clones from 8 cases of acute
      hepatitis B without hepatic failure serving as controls. The source of infection
      was traceable in 3 cases. The same precore-region defect, along with the sequence
      identity of 435 nucleotides, was observed in clones from the case of a baby and
      his grandmother, who carried the virus and was implicated in the transmission,
      and also in clones from two pediatricians and the carrier patients they attended.
      These findings support the hypothesis that precore-defective mutants have
      stronger activity to induce fulminant hepatitis than nondefective viruses.

PMID- 2001808
TI  - Direct measurement of first-pass ileal clearance of a bile acid in humans.
AB  - The purpose of this study was to develop and validate a method of directly
      measuring ileal bile acid absorption efficiency during a single enterohepatic
      cycle (first-pass ileal clearance). This has become feasible for the first time
      because of the availability of the synthetic gamma-labeled bile acid 75Selena
      homocholic acid-taurine (75SeHCAT). Together with the corresponding natural bile
      acid cholic acid-taurine (labeled with 14C), SeHCAT was infused distal to an
      occluding balloon situated beyond the ampulla of Vater in six healthy subjects.
      Completion of a single enterohepatic cycle was assessed by obtaining a plateau
      for 75SeHCAT activity proximal to the occluding balloon, which prevented further
      cycles. Unabsorbed 75SeHCAT was collected after total gut washout, which was
      administered distal to the occluding balloon. 75SeHCAT activity in the rectal
      effluent measured by gamma counter was compared with that of absorbed 75SeHCAT
      level measured by gamma camera and was used to calculate first-pass ileal
      clearance. This was very efficient (mean value, 96%) and showed very little
      variation in the six subjects studied (range, 95%-97%). A parallel time-activity
      course in hepatic bile for 14C and 75Se during a single enterohepatic cycle,
      together with a ratio of unity for 14C/75Se in samples obtained at different time
      intervals, suggests that 75SeHCAT is handled by the ileum like the natural bile
      acid cholic acid-taurine. Extrapolation of 75SeHCAT first-pass ileal clearance to
      that of the natural bile acid therefore seems justifiable. In a subsidiary
      experiment, ileal absorption efficiency per day for 75SeHCAT was also measured by
      scanning the gallbladder area on 5 successive days after the measurement of first
      pass ileal clearance. In contrast with absorption efficiency per cycle,
      absorption efficiency per day varied widely (49%-86%), implying a possible wide
      variation in recycling frequency per day.

PMID- 2001809
TI  - Quantitative cholescintigraphy in the assessment of choledochoduodenal bile flow.
AB  - Quantitative cholescintigraphy has been proposed as a noninvasive method to
      assess function of the sphincter of Oddi in cholecystectomized subjects. The
      present study evaluated several quantitative cholescintigraphic variables to
      assess their time-related variability as well as their capability to detect delay
      of choledochoduodenal bile flow. Cholescintigraphy with 2,6
      diethylphenylcarbahoylmethyl diacetic acid 99mTc was performed in 24
      cholecystectomized patients with recurrent biliary-like pain, laboratory evidence
      of bile stasis, normal hepatocellular function tests, and no evidence of
      choledocholithiasis. The study was also performed in 26 asymptomatic
      cholecystectomized subjects and repeated at 2-week intervals during identical
      experimental conditions in 10 of them. Of the following quantitative
      cholescintigraphic variables investigated, (a) hepatic T peak, (b) 50% hepatic
      retention (T peak, 1/2), (c) percent hepatic retention at 30 minutes, (d) percent
      hepatic retention at 40 minutes, (e) vein-hepatic hilum transit time, (f) vein
      duodenum transit time, and (g) hepatic hilum-duodenum transit time, only the
      hepatic hilum-duodenum transit time showed a statistically significant
      correlation between the duplicate studies. Only vein-duodenum transit time and
      hepatic hilum-duodenum transit time discriminated the symptomatic from the
      asymptomatic patients; of the two variables, however, hepatic hilum-duodenum
      transit time showed less intrasubject variability and no overlap between the two
      groups of patients. Hepatic hilum-duodenum transit time showed a positive linear
      correlation with the maximum diameter of the choledochus. It is concluded that in
      cholecystectomized patients, the hepatic hilum-duodenum transit time appears to
      detect a delay of bile flow into the intestine better than any other
      cholescintigraphic variable. However, in patients with a dilated common bile
      duct, this variable cannot discriminate bile flow delay due to increased
      choledochal capacity and/or obstruction of the sphincter of Oddi.

PMID- 2001810
TI  - Overt hepatic encephalopathy precipitated by zinc deficiency.
AB  - Encephalopathy in liver disease may be unresponsive to protein restriction,
      lactulose, and neomycin. Zinc supplements have been reported to improve
      psychometric performance in liver cirrhosis, but the importance of zinc
      deficiency in overt hepatic encephalopathy has not yet been clearly established.
      A patient with severe recurrent hepatic encephalopathy was studied to determine
      the relation between her signs of encephalopathy and zinc deficiency. The study
      included a period in which zinc deficiency was artificially induced by oral
      histidine. An episode of overt encephalopathy occurred that was identical to
      earlier episodes and responded to oral zinc. The study showed an association
      between encephalopathy and zinc deficiency by successive zinc depletion and
      supplementation regimens. Long-term zinc supplementation improved severe
      recurrent hepatic encephalopathy and therefore the quality of life.

PMID- 2001811
TI  - Nonsteroidal antiinflammatory drug-induced colonic strictures: a case report.
AB  - Adverse effects of nonsteroidal antiinflammatory drugs can occur throughout the
      whole gastrointestinal tract. Recently, several cases of "diaphragmlike" thin
      ileal strictures have been reported. These strictures seem to result from
      nonsteroidal antiinflammatory drug-induced inflammatory changes and apparently
      represent a newly recognized nosological entity. The case of a 61-year-old man
      who gradually developed similar inflammatory changes in the ascending colon
      during prolonged intake of a slow-release form of diclofenac is presented, and
      the literature on nonsteroidal antiinflammatory drug-induced intestinal
      strictures is briefly reviewed.

PMID- 2001812
TI  - Intrahepatic cholestasis of pregnancy and acute fatty liver of pregnancy. An
      unusual but favorable association?
AB  - During the 26th week of a first pregnancy, a 25-year-old woman presented with
      pruritus suggesting an intrahepatic cholestasis of pregnancy. The pruritus,
      however, persisted despite the premature delivery of a normal newborn at the 35th
      week. Moreover, aspartate aminotransferase activity increased, reaching a maximum
      of 38 times normal level on the 17th day after the delivery. Thus, an acute fatty
      liver of pregnancy was suspected and confirmed by liver biopsy. This patient
      appeared to have both intrahepatic cholestasis of pregnancy and acute fatty liver
      of pregnancy, an association not previously reported. It is suggested that
      intrahepatic cholestasis of pregnancy caused premature delivery, which in turn
      may have prevented the onset of severe maternal and fetal complications caused by
      acute fatty liver of pregnancy.

PMID- 2001813
TI  - Does auxiliary heterotopic liver transplantation reverse hypersplenism and portal
      hypertension?
AB  - In this study, performed to assess the effect of auxiliary heterotopic liver
      transplantation on portal hypertension and hypersplenism, eight patients with
      chronic liver disease who underwent the procedure and had functioning grafts for
      at least 6 months were analyzed. The transplantation resulted in (a)
      normalization of platelet and leukocyte counts, (b) reduction of splenomegaly by
      20% +/- 3% (P less than 0.02), (c) disappearance of ascites, and (d) diminution
      of esophageal varices in all patients. Intraoperatively, the mean portacaval
      pressure gradient decreased with 54% +/- 7% after recirculation of the graft (P
      less than 0.05). In conclusion, a functioning auxiliary heterotopic liver graft
      decompresses portal hypertension and reverses hypersplenism.

PMID- 2001814
TI  - Clinical differentiation of fulminant Wilsonian hepatitis from other causes of
      hepatic failure.
AB  - Establishing a diagnosis of fulminant Wilson's disease can be difficult because
      Kayser-Fleischer rings may not be present and parameters of copper metabolism,
      including serum and urinary copper, and serum ceruloplasmin levels are neither
      specific nor diagnostic. In this study, ratios of both the serum alkaline
      phosphatase to total bilirubin and aspartate transaminase to alanine transaminase
      were constructed to evaluate their usefulness in differentiating fulminant
      hepatic failure caused by Wilson's disease (n = 6) from other etiologies (n =
      43). An analysis of the data showed that cutoff values of less than 2.0 for the
      alkaline phosphatase-total bilirubin ratio and greater than 4.0 for the aspartate
      transaminase ratio were associated with a diagnosis of fulminant hepatic failure
      caused by Wilson's disease only (P less than 0.001). The alkaline phosphatase
      total bilirubin ratio of less than 2.0 provided 100% sensitivity and specificity
      in identifying fulminant hepatic failure caused by Wilson's disease from other
      types of fulminant hepatic failure.

PMID- 2001815
TI  - Introduction of monoclonal antibodies to bromodeoxyuridine to monitor hepatic
      regeneration.
AB  - The effect on the liver of portal vein and/or bile duct branch ligation was
      examined in rabbits by measuring cellular kinetics using the bromodeoxyuridine
      labeling index. Twenty-four days after ligation of a portal vein and/or bile duct
      branch, similar degrees of compensatory regeneration were observed. However,
      there were significant differences in the pattern in which regeneration
      developed. Compensatory regeneration after ligation of a bile duct follows a
      different pattern than that after portal vein branch ligation.

PMID- 2001816
TI  - Hepatitis B virus unable to secrete e antigen.

PMID- 2001817
TI  - Hyperplastic colon polyps do not predict adenomas.

PMID- 2001818
TI  - Weight reduction and metabolic rate: good news for obese patients?

PMID- 2001819
TI  - Intestinal lymphangiectasia: lack of efficacy of antiplasmin therapy?

PMID- 2001820
TI  - Involvement of tumor necrosis factor alpha in experimentally induced hepatitis.

PMID- 2001821
TI  - Relation among personality and symptoms in nonulcer dyspepsia and the irritable
      bowel syndrome.

PMID- 2001822
TI  - Effects of capsaicin on ethanol damage in the rat.

PMID- 2001823
TI  - Iatrogenic ruptures of the stomach after balloon tamponade--two case reports.

PMID- 2001824
TI  - Omeprazole and the induction of human cytochrome P-450: a response to concerns
      about potential adverse effects.

PMID- 2001825
TI  - Hypertrophic smooth muscle in the partially obstructed opossum esophagus. The
      model: histological and ultrastructural observations.
AB  - Obstruction is a complication of many esophageal diseases, but the morphological
      changes occurring in the obstructed esophagus are poorly understood. We developed
      a model of esophageal obstruction in the American opossum, Didelphis virginiana.
      A nonconstricting band around the gastroesophageal junction led to esophageal
      distention and tortuosity in the weeks following its placement. Despite a marked
      increase of the esophageal circumference, the esophageal wall was not thinned,
      and the circular muscle layer had actually increased its thickness. This was due
      to an increase in the size of individual smooth muscle cells with proportional
      increases in the cell surface area and volume. The electron density of
      hypertrophic smooth muscle cells varied much more than that of normal esophageal
      smooth muscle cells. As cell size increased, the tissue became more compact and
      the size of the extracellular space decreased. Also, the extracellular space was
      filled by an amorphous electron-dense material. Additional changes in the
      structure of hypertrophic smooth muscle cells included prominent intermediate
      filaments in the vicinity of thick filaments. There was no difference in the
      structure of the hypertrophic smooth muscle at 4 weeks and at 8 weeks after
      placement of the band. The morphological features described here resemble those
      seen in human esophageal spasm and achalasia of humans and could affect
      esophageal smooth muscle function.

PMID- 2001826
TI  - Nocturnal intragastric acidity during and after a period of dosing with either
      ranitidine or omeprazole.
AB  - The magnitude and duration of changes in nocturnal intragastric acidity caused by
      25 days of dosing with the antisecretory drugs ranitidine and omeprazole were
      investigated in a double-blind study of 22 healthy subjects. Nocturnal
      intragastric acidity was studied before (twice), during (on day 25), and after
      (every 3 days for 21 days) dosing with either 300 mg ranitidine at night or 40 mg
      omeprazole every morning. Three and six days after withdrawal of dosing with
      ranitidine, median integrated nocturnal intragastric acidity was increased
      significantly (17% and 14%, P = 0.01 and P = 0.05, respectively) compared with
      before dosing. Three days after withdrawal of dosing with omeprazole, median
      integrated nocturnal intragastric acidity was decreased significantly (-23%, P =
      0.003). Compared with before dosing, no significant differences were seen in the
      ranitidine group between days 9 and 21 or the omeprazole group between days 6 and
      21 after cessation of dosing. Fasting plasma gastrin concentration was measured
      on the morning of each study; compared with before treatment, the only
      significant elevations occurred on the last day of dosing with omeprazole
      (before, 4 pmol/L; during, 7 pmol/L). It is concluded that rebound intragastric
      hyperacidity after dosing with 300 mg ranitidine at night or sustained
      hypoacidity after dosing with 40 mg omeprazole every morning reflect transient
      disturbances of gastric function that are unlikely to be of clinical importance.

PMID- 2001827
TI  - Gastric injury and invasion of parietal cells by spiral bacteria in rhesus
      monkeys. Are gastritis and hyperchlorhydria infectious diseases?
AB  - The possibility of using the rhesus monkey as a model for studying gastric
      function in the presence of infection with spiral bacteria was studied.
      Endoscopic evaluation of the gastric mucosa was performed under general
      anesthesia in 29 colony-bred rhesus monkeys, and gastric pinch biopsy specimens
      were obtained from each animal. On a separate day, gastric emptying and acid
      output were determined using a 99mTc dilution technique. Biopsy samples were
      fixed for light microscopy (H&E, Gram, and Warthin-Starry stains) and for
      transmission electron microscopy. The presence of spiral bacteria and gastritis
      was assessed and rated on coded slides. In 8 of 29 monkeys, Helicobacter pylori
      like organisms were observed in close proximity to the mucosal epithelial cells
      or in the lumen of the gastric pits. In 14 other monkeys, "Gastrospirillum
      hominis"-like organisms were observed in the mucus covering the surface of
      epithelial cells, in the lumina of the gastric glands, and overlying parietal
      cells. Gastritis was present in 8 of 8 animals positive for H. pylori-like
      organisms, in 2 of 14 animals positive for "G. hominis"-like organisms, and in
      none of the uninfected monkeys, and the mean gastritis index was significantly
      greater in animals positive for H. pylori-like organisms. Moreover, acid output
      was significantly higher in monkeys positive for "G. hominis"-like organisms than
      in controls or animals positive for H. pylori-like organisms. Gastric emptying
      was not significantly different in the three groups. In conclusion, (a) H. pylori
      like, but not "G. hominis"-like, organisms cause gastritis while not modifying
      acid output; (b) "G. hominis"-like, but not H. pylori-like organisms, invade and
      on occasion damage parietal cells while apparently causing hyperchlorhydria; and
      (c) the rhesus monkey appears to be a good model for the study of gastric
      infection with spiral bacteria.

PMID- 2001828
TI  - Disturbed gastroduodenal motility in patients with active and healed duodenal
      ulceration.
AB  - Disordered gastroduodenal motility may promote duodenal ulceration by allowing
      prolonged acid contact with the duodenal mucosa. Using a multilumen perfused
      catheter incorporating 3 pH microelectrodes, antral and duodenal pH and
      antropyloroduodenal pressure activity were recorded in 36 subjects (10 with
      healed duodenal ulceration, 11 with active duodenal ulceration, and 15 healthy
      volunteers) during fasting and after a radiolabeled solid test meal. Correct pH
      probe/catheter position was continuously verified by recording transmucosal
      potential difference across the pylorus. Patients with active and healed duodenal
      ulcer had similarly disordered gastroduodenal motility. The chief abnormalities
      consisted of an increase in postprandial duodenal retroperistalsis (healed
      duodenal ulceration, 12 +/- 1 events per hour; active duodenal ulceration, 12 +/-
      1; control, 6 +/- 1; mean +/- SEM: healed and active duodenal ulceration vs.
      control, P = 0.004 and P = 0.03, respectively), a reduction in pressure waves
      sweeping aborally through the duodenum after the meal (healed duodenal
      ulceration, 22 +/- 4 events per hour; active duodenal ulceration, 23 +/- 3;
      control, 34 +/- 4: healed and active duodenal ulceration vs. control, P = 0.04
      and P less than 0.05, respectively), and an increased incidence of atypical,
      complex forms of coordinated duodenal motor activity throughout the study
      (postprandial data; healed duodenal ulceration, 8 +/- 1 events per hour; active
      duodenal ulceration, 10 +/- 1; control, 4 +/- 1: healed and active duodenal
      ulceration vs. control, P = 0.02 and P less than 0.02, respectively). In
      addition, gastric emptying of the solid test meal was significantly delayed in
      healed, but not active, duodenal ulceration [half-emptying time, healed duodenal
      ulceration 185 minutes (117-235); active duodenal ulceration 102 minutes (80
      200); control 107 minutes (78-130): healed duodenal ulceration vs. control, P
      less than 0.009]. Duodenal bulb pH was similar in controls and patients with
      active duodenal ulceration; however, bulb pH was less than 4 for a significantly
      greater period of time in healed duodenal ulceration compared with active ulcer
      patients, particularly after the meal. In conclusion, duodenal ulcer disease is
      associated with disturbed gastroduodenal motility, even when the ulcer is
      quiescent and when intraduodenal acidity is low. In healed duodenal ulceration,
      disturbed motility may promote ulcer relapse by impairing acid clearance from the
      bulb. However, in active ulceration other factors such as mucosal bicarbonate
      secretion may have a more influential role in determining intraduodenal pH.

PMID- 2001829
TI  - Intestinal vascular sensitivity to vasopressin in portal hypertensive rats.
AB  - The intestinal vascular responsiveness to arginine vasopressin was evaluated in
      rats with chronic portal hypertension. Male Sprague-Dawley rats were made portal
      hypertensive by stenosis of the portal vein. Ten to twelve days after the
      induction of chronic portal hypertension, the responsiveness of the small
      intestinal circulation to cumulative doses of vasopressin was evaluated using an
      isolated pump-perfused small intestinal preparation. The ED50 for maximal
      vasoconstriction was increased twofold in portal hypertensive rats compared with
      control rats. To determine if the impaired responsiveness to arginine vasopressin
      was related to the hyperglucagonemia of chronic portal hypertension, plasma
      glucagon levels were elevated in normal rats to levels previously measured in
      portal hypertensive rats (i.e. approximately 450 pg/mL), and the dose response
      studies were repeated. Glucagon significantly attenuated the responsiveness of
      the intestinal vasculature to vasopressin. Equipotent doses of nitroprusside also
      attenuated intestinal vascular responsiveness to vasopressin. The results
      indicate that there is a reduced vascular sensitivity to vasopressin in the
      intestine of portal hypertensive animals and suggest that elevations in
      circulating vasodilators in portal hypertensive conditions may partially explain
      this altered vascular responsiveness.

PMID- 2001830
TI  - Macrophage engulfment of mucosal mast cells in rats treated with dexamethasone.
AB  - The effects of corticosteroid treatment on mucosal mast cells in rat jejunal
      mucosa were examined. Rats previously infected with Nippostrongylus brasiliensis
      received a single IP injection of 1 mg dexamethasone. Three hours later, one
      third of mucosal mast cells demonstrated minor granular changes (fusion or
      peripheral clear zones) by electron microscopy. At 7 hours, by light microscopy,
      the majority of mucosal mast cells appeared abnormal with clustering of granules.
      By electron microscopy, 151 of 233 (65%) mucosal mast cells had been engulfed by
      enlarged macrophages and were in various stages of degeneration inside large
      phagosomes. By 24 hours, the number of mucosal mast cells had decreased to less
      than 10% of the initial number with parallel decreases in tissue rat mast cell
      protease II and histamine levels. Serum levels of rat mast cell protease II did
      not increase, and intestinal morphology was invariably normal with no evidence of
      inflammatory changes up to and including 24 hours. Observations were similar in
      uninfected animals. In contrast, in rats undergoing antigen-induced anaphylaxis,
      a significant elevation of serum rat mast cell protease II level was evident at 3
      and 7 hours, and macrophage engulfment of mucosal mast cells was never seen,
      although tissue edema, enterocyte loss, and hemorrhage were observed. It is
      concluded that dexamethasone treatment results in macrophage engulfment and
      destruction of mucosal mast cells that occurs without granular mediator release
      and local inflammatory effects.

PMID- 2001831
TI  - Colonic motor activity in acute colitis in conscious dogs.
AB  - The changes in motor activity of the colon during acute colitis were investigated
      in six conscious dogs. The motor activity was recorded with seven strain-gauge
      transducers. Colitis was induced in the entire colon by luminal perfusion of
      acetic acid. The dogs exhibited urgency and diarrhea with mucus and blood during
      colitis. The mucosa was diffusely erythematous and friable and there were
      scattered ulcerations over the mucosal surface. The motor activity of the colon
      changed in several ways during colitis: (a) the total duration per hour and the
      mean duration of contractile states decreased significantly; (b) the cycle length
      of colonic migrating motor complexes was significantly prolonged, and the
      nonmigrating motor complexes were almost completely absent; and (d) the incidence
      of giant migrating contractions increased significantly. About half of the giant
      migrating contractions were followed by defecation. The remaining expelled mucus
      or gas. Sometimes, a migrating motor complex in the colon was also followed by
      defecation; this was never observed in the normal state. The motor activity of
      the colon was still decreased and the cycle length prolonged 21 days after
      induction of colitis. However, the dogs were asymptomatic at this time and the
      mucosa looked normal at colonoscopy. The incidence of giant migrating
      contractions was also normal at this time. It was concluded that the dog is a
      good model for the study of colitis because of the similarity of symptoms with
      human ulcerative colitis. The phasic contractions of the colon decreases during
      colitis but the incidence of giant migrating contractions is increased. The
      diarrhea in colitis may primarily be due to the large number of giant migrating
      contractions in the middle and the distal colon.

PMID- 2001832
TI  - Conditioned emotional response in rats enhances colonic motility through the
      central release of corticotropin-releasing factor.
AB  - The effect of a mental stress model corresponding to conditioned fear on
      cecocolonic motility was evaluated electromyographically in intact and
      hypophysectomized rats equipped with electrodes implanted in the cecum and
      proximal colon over a long period and a small polyethylene catheter inserted into
      the right lateral ventricle of the brain. Intact fasted and fed rats showed an
      increase of 82.3% and 67.2%, respectively, in colonic spike-burst frequency when
      placed for 30 minutes in a box in which they had previously received electrical
      shocks in their feet. Intracerebroventricular administration of corticotropin
      releasing factor (0.5 micrograms/kg) mimicked the effects of mental stress and
      increased cecocolonic spike-burst frequency by 75.8%. The specific corticotropin
      releasing factor receptor antagonist alpha-helical CRF9-41 given
      intracerebroventricularly (5 micrograms/kg) prevented both the effects of mental
      stress and corticotropin-releasing factor (0.5 micrograms/kg
      intracerebroventricularly) on colonic spike-burst frequency. In contrast,
      diazepam (0.5 mg/kg IM) suppressed colonic hypermotility induced by mental stress
      but not that resulting from intracerebroventricular injection of corticotropin
      releasing factor (0.5 micrograms/kg). Increased colonic spike-burst frequency
      induced either by stress or by central administration of corticotropin-releasing
      factor was not prevented by hypophysectomy. It was concluded that mental stress
      increases the frequency of cecocolonic spike-burst activity and that these
      effects are related to the central release of corticotropin-releasing factor
      because they are blocked by a corticotropin-releasing factor antagonist and
      reproduced by intracerebroventricular administration of corticotropin-releasing
      factor. Moreover, mental stress-induced colonic motor alterations are mediated by
      the autonomic nervous system rather than by the hypothalamopituitary axis because
      they are not abolished by hypophysectomy.

PMID- 2001833
TI  - Comparison of collagen propeptides as growth markers in children with
      inflammatory bowel disease.
AB  - The serum concentrations of the carboxy-terminal propeptide of type I procollagen
      and the amino-terminal propeptide of type III procollagen as biochemical markers
      of growth activity were compared in 46 children and adolescents with inflammatory
      bowel disease. Significant correlations were noted between growth velocity and
      type I procollagen (r = 0.65; P less than 0.001) and type III procollagen
      concentrations (r = 0.64; P less than 0.001). Although the serum concentration of
      type I procollagen was generally about 15 times greater than that of type III,
      the respective serum concentrations were highly correlated (r = 0.66; P less than
      0.001) at all growth velocities. The use of daily corticosteroid therapy was
      associated with significantly lower concentrations of both propeptides (P less
      than 0.01) than was alternate-day or no corticosteroid therapy, respectively.
      Children with growth arrest (0.0 cm/mo) had type I and type III procollagen
      concentrations similar to those found in adults. These observations indicate that
      the serum concentrations of both collagen propeptides reflect growth activity in
      children with inflammatory bowel disease and suggest that routine measurement of
      collagen propeptides may have clinical value in monitoring normal and abnormal
      growth. The data suggest that the measurement of one propeptide does not offer an
      advantage over the other.

PMID- 2001834
TI  - Adenovirus colitis in the acquired immunodeficiency syndrome.
AB  - Adenovirus was identified in colonic tissue by transmission electron microscopy
      or culture in 5 of 67 (7.4%) homosexual men seropositive for human
      immunodeficiency virus (51 with the acquired immunodeficiency syndrome) with
      diarrhea. Colonoscopy showed the mucosa to be normal in 3 cases and mildly
      inflamed in 2. Light microscopy showed foci of mucosal necrosis that contained
      chronic inflammatory cells and degenerating and necrotic epithelial cells with
      amphophilic nuclear inclusions. By transmission electron microscopy, hexagonal
      viral particles characteristic of adenovirus were identified within the
      inclusions. Only 1 patient was concomitantly infected by a second potential
      enteric pathogen. It was concluded that adenovirus, an uncommon enteric pathogen
      in immunocompetent adults, causes intestinal pathology and may be associated with
      diarrheal illness in persons with the acquired immunodeficiency syndrome.

PMID- 2001835
TI  - Perinatal changes in bombesin-stimulated muscle contraction in rabbit stomach and
      colon.
AB  - Bombesin and its mammalian homologue, gastrin-releasing peptide, stimulate smooth
      muscle contraction and may promote the growth of gastrointestinal tissues.
      Isometric contraction of strips from circular muscle of the gastric fundus and
      longitudinal muscle of the distal colon were used to compare changes in the
      response to bombesin in newborn and weanling rabbits. There was an age-related
      qualitative change in gastric muscle from biphasic contractions including phasic
      and tonic components in the newborn to phasic contractions alone in the weanling.
      The colon contractions were tonic at both ages. In both tissues there was an age
      related fivefold increase in stress in response to maximally effective
      concentrations of bethanechol (P less than 0.05). In contrast, in the stomach age
      related decreases in the response to maximally effective concentrations of
      bombesin were observed, from 2930 +/- 179 mN/cm2 (98% of the maximal response to
      bethanechol) in the newborn to 565 +/- 81 mN/cm2 (4% of the maximal response to
      bethanechol) in the weanling (P less than 0.005). In the colon, a twofold
      increase in response to bombesin was observed, from 446 +/- 59 mN/cm2 (82% of the
      response to bethanechol) in the newborn to 862 +/- 11 mN/cm2 (29% of the response
      to bethanechol) in the weanling (P less than 0.05). No age-related changes were
      observed in the potency of bombesin in either tissue. Neither atropine nor
      tetrodotoxin altered the contractions in either tissue, suggesting that bombesin
      interacted directly with myocytes. There was three times as much bombesinlike
      immunoreactivity in the stomach compared with the colon, but no age-related
      changes in either tissue. In summary, by the age of weanling the stomach lost the
      tonic component of contraction and 80% of the efficacy of bombesin-stimulated
      phasic contraction that had been present in the newborn. The loss of efficacy,
      absolute in the stomach and relative to bethanechol in the colon, suggest that
      bombesin may be most important in stimulating motility in the neonatal period.

PMID- 2001836
TI  - Mucin and nonmucin secretagogue activity of Entamoeba histolytica and cholera
      toxin in rat colon.
AB  - Depletion of colonic mucus occurs before invasion of the colonic mucosa by
      Entamoeba histolytica trophozoites. It is hypothesized that E. histolytica
      releases a mucus secretagogue; this was studied in a rat colonic loop model. In
      colonic loops exposed to live amebae, mucus secretion was quantitated by release
      of acid-precipitable [3H]glucosamine-labeled luminal glycoprotein and by specific
      immunoassay. Mucus secretion increased in dose-dependent fashion in response to
      greater than or equal to 1 X 10(5) trophozoites; cholera toxin (20 micrograms per
      loop), a known mucus secretagogue, elicited a similar response. Thin-section
      histological analysis of amebae and cholera toxin-exposed loops showed increased
      mucus release and streaming from mucosal goblet cells with cellular cavitation
      compared with control loops. Sepharose-4B chromatography of amebae and cholera
      toxin-stimulated glycoproteins demonstrated secretion of mucins and an 80%-90%
      increase in low-molecular-weight proteins. E. histolytica trophozoites and
      cholera toxin enhanced the secretion of preformed and newly synthesized mucin
      glycoproteins and stimulated colonic glycoprotein synthesis. The level of mucus
      secretion elicited by axenic E. histolytica strains correlated with their
      virulence in vivo and in vitro. The amebic secretagogue was released into the
      culture medium and was heat stable. Mucus secretagogue activity of E. histolytica
      may contribute to depletion or alteration of the protective mucus blanket,
      facilitating pathogenesis of invasive amebiasis.

PMID- 2001837
TI  - Irritable bowel syndrome in office-based practice in the United States.
AB  - United States estimates of the frequency of visits to physicians and patterns of
      medical care for the diagnosis of the irritable bowel syndrome were derived from
      the 1975, 1980-1981, and 1985 National Ambulatory Medical Care Surveys. These
      surveys of office-based physicians allow national estimates of various aspects of
      ambulatory care. The overall rate of visits with the diagnosis of irritable bowel
      syndrome in 1980-1981 and 1985 were 10.6 per thousand U.S. population. Women had
      2.4 times the rate of visits by men and rates rose in both sexes until middle
      age. Irritable bowel syndrome was the leading digestive disease diagnosis among
      gastroenterologists but only the seventh leading diagnosis among all physicians.
      Gastrointestinal symptoms, association with mental disorders, prescriptions, and
      disposition were also examined in patients with visits for irritable bowel
      syndrome. Among records with digestive tract symptoms and a first listed
      diagnosis of irritable bowel syndrome, stomach or abdominal pain was listed on
      only about one half of records and disorders of bowel function were listed on
      fewer than 40%. In 1975 and 1985, irritable bowel syndrome was noted
      approximately twice as often as other digestive diseases at visits with mental
      disorder symptoms and diagnosis, although mental disorder symptoms and diagnoses
      were noted at fewer than 15% of visits with irritable bowel syndrome. Medications
      were prescribed at approximately 75% of visits for irritable bowel syndrome; the
      most common were gastrointestinal medications followed by combination
      gastrointestinal-psychoactive medications. Subsequent appointments were scheduled
      following at least 50% of the visits of patients with irritable bowel syndrome.

PMID- 2001838
TI  - wimp, a dominant maternal-effect mutation, reduces transcription of a specific
      subset of segmentation genes in Drosophila.
AB  - wimp is a dominant maternal-effect mutation that interacts with a specific subset
      of early-acting maternal and zygotic Drosophila genes. We show that wimp is a
      change-of-function mutation, allelic to mutations of the 140-kD subunit of RNA
      polymerase, which causes reduced transcription of interacting genes. Loci that do
      not interact with wimp are expressed at normal levels. We discuss these results
      in terms of specific interactions between transcription factors and RNA
      polymerase. Embryos from wimp mothers show unaltered fate maps and develop
      normally, despite the reduction of transcript levels at least twofold. We suggest
      that spatial cues are determined by a balance of segmentation gene products
      rather than their absolute concentrations. We also demonstrate powerful genetic
      screens for otherwise undetected loci required for segmentation, sex
      determination, and other early functions.

PMID- 2001839
TI  - v-myb and v-ets transform chicken erythroid cells and cooperate both in trans and
      in cis to induce distinct differentiation phenotypes.
AB  - E26 is an acute avian leukemia virus that encodes the transcriptional activator
      oncogenes v-myb and v-ets in a single fusion protein. This virus is also unique
      in that it is able to transform hematopoietic cells of both the myeloid and the
      erythroid lineage. To determine the contributions of v-myb and v-ets to the
      transforming potential of the virus, derivatives expressing separate Myb and Ets
      proteins, either alone or in combination, were constructed. We found that in the
      myeloid lineage v-myb, but not v-ets, induces cell transformation. In the
      erythroid lineage both v-myb and v-ets weakly transform erythroblast-like cells.
      These cells exhibit a mature phenotype and a low self-renewal capacity. The
      transforming efficiency of the two oncogenes is enhanced if they are coexpressed
      as separate proteins or as a fusion protein, the transformed cells displaying an
      increased self-renewal capacity. Interestingly, however, cells transformed by the
      Myb-Ets fusion protein have a distinct phenotype in that they are very immature.
      These results demonstrate that v-myb and v-ets can cooperate in the
      transformation of erythroid cells both in trans and in cis and that the mode of
      cooperation is reflected by the differentiation phenotypes of the transformed
      cells.

PMID- 2001840
TI  - Expression of two members of the Wnt family during mouse development--restricted
      temporal and spatial patterns in the developing neural tube.
AB  - The Wnt gene family encodes a group of cysteine-rich proteins implicated in
      intercellular signaling during several stages of vertebrate development. This
      family includes Wnt-1 and Wnt-3, both discovered as activated oncogenes in mouse
      mammary tumors. Here we describe the molecular cloning of an additional member of
      the Wnt family, called Wnt-3A, and the spatial and temporal expression pattern of
      this gene as well as that of its close relative Wnt-3. The putative amino acid
      sequences of both proteins are almost 90% identical, but in situ hybridization to
      mouse embryo sections showed highly restricted patterns of expression of Wnt-3
      and Wnt-3A, largely in separate areas in the developing nervous system. In the
      spinal cord Wnt-3 was expressed at low levels in the alar laminae and in the
      ventral horns, whereas Wnt-3A expression was confined to the roof plate. In the
      developing brain Wnt-3 was expressed broadly across the dorsal portion of the
      neural tube with a rostral boundary of expression at the diencephalon. In
      contrast, Wnt-3A was expressed in a narrow region very close to the midline;
      expression extended into the bifurcating telencephalon, in a highly localized
      fashion. Both Wnt-3 and Wnt-3A were expressed in the ectoderm, and Wnt-3A was
      also expressed in the periumbilical mesenchyme. Characteristic expression
      patterns of these two closely related genes suggest that Wnt-3 and Wnt-3A play
      distinct roles in cell-cell signaling during morphogenesis of the developing
      neural tube.

PMID- 2001841
TI  - Does steric interference between splice sites block the splicing of a short c-src
      neuron-specific exon in non-neuronal cells?
AB  - The neuron-specific splicing of the mouse c-src N1 exon was analyzed. Model src
      genes, transiently expressed in HeLa and LA-N-5 neuroblastoma cells, were assayed
      for the insertion of the 18-nucleotide neuron-specific N1 exon into their product
      mRNA. The normal clone fails to use this exon in HeLa cells but inserts the exon
      into 50% of the mature mRNA in LA-N-5 cells. When the exon and flanking intron
      sequences are placed between two adenovirus exons, the N1 exon is still only
      inserted in the neural cells. Thus, the neural specificity is a property of the
      exon itself and its immediate flanking sequences. Simply extending the length of
      the N1 exon to 109 nucleotides allows its efficient use in HeLa cells, implying
      that the exon is normally skipped because it is too short to allow spliceosomes
      to assemble at both ends simultaneously. This model predicts that exclusion of
      the exon should be sensitive to proteins or mutations that alter the relative
      strength of the flanking splice sites. Mutations that change these splice sites
      support this hypothesis.

PMID- 2001843
TI  - Inactivation of auxin in tobacco transformed with the indoleacetic acid-lysine
      synthetase gene of Pseudomonas savastanoi.
AB  - The iaaL gene of Pseudomonas syringae, subspecies savastanoi, encodes an
      indoleacetic acid (IAA)-lysine synthetase. To determine the effects of converting
      IAA to IAA-lysine in whole plants, the iaaL gene was fused to a constitutive
      plant promoter and introduced into tobacco plants. Biochemical analyses show that
      endogenous IAA is reduced by up to 19-fold in iaaL plants. Tobacco plants
      expressing the iaaL gene display reduced apical dominance, reduced rooting, and
      inhibition of vascular differentiation. The phenotypic effects of iaaL gene
      expression are reverted by crossing iaaL plants with plants that overproduce IAA.
      These data indicate that iaaL can act as an anti-auxin gene in vivo and confirm
      the role of auxin in the control of apical dominance, root growth, and vascular
      differentiation in whole plants.

PMID- 2001842
TI  - Identification of a potent adipocyte-specific enhancer: involvement of an NF-1
      like factor.
AB  - The molecular basis for adipocyte-specific gene expression is not known. We have
      demonstrated that while short (-168) segments of the 5'-flanking sequence of the
      adipocyte P2 gene containing AP-1- and C/EBP-binding sites can direct expression
      of a heterologous gene in cultured adipocytes, they cannot support tissue
      specific expression in a transgenic mouse. We have therefore analyzed larger
      segments of the aP2 5'-flanking region by transfection into adipocytes and have
      found an enhancer at -5.4 kb. This 500-bp enhancer directs expression of the
      bacterial chloramphenicol acetyltransferase (CAT) gene in a differentiation
      dependent fashion when linked to its own minimal promoter or to an enhancerless
      SV40 promoter. Moreover, this enhancer stimulates very strong and highly specific
      expression from the CAT gene in the adipose tissues of transgenic mice. A smaller
      fragment (190 bp) having enhancer activity in adipocytes was defined and
      demonstrated to contain a binding site for an abundant nuclear protein. This
      factor has the binding specificity and several other properties characteristic of
      the nuclear factor 1 (NF-1) transcription/replication factor family, and mutation
      of this NF-1-binding site greatly reduces the function of the 500-bp enhancer.
      These results identify and characterize the first functional enhancer with
      specificity for adipose cells and also demonstrate that a member(s) of the NF-1
      family is involved in adipocyte-specific gene expression.

PMID- 2001844
TI  - Support and psychoeducation for parents of hospitalized mentally ill children.
AB  - Support and psychoeducational techniques were used in a group for parents of
      children hospitalized for psychiatric reasons. The parent's group model extends
      from more traditional, supportive, expressive group treatment to the use of
      didactic, concrete, cognitive components similar to the psychoeducational model
      used for families of mentally ill adults. Skills for dealing with limit setting,
      anger, and discipline were taught in a group climate that allowed for full
      expression of parental concerns. Guidelines for such a group program, including
      parent management techniques, are provided. The combination of modalities is the
      model's strength.

PMID- 2001845
TI  - Needs of homeless people coping with psychiatric problems: findings from an
      innovative advocacy project.
AB  - In this article the authors report on the self-perceived needs of 40 homeless
      people who are coping with psychiatric problems. These people were among 207 with
      psychiatric problems participating in an innovative advocacy project based
      outside the formal mental health system. Compared with domiciled participants,
      the homeless participants had more accentuated and somewhat different major daily
      living needs in the areas of income and benefits, housing, legal services,
      employment, and health care. On the basis of these findings, the authors draw
      implications for social work practice with homeless people coping with
      psychiatric problems.

PMID- 2001846
TI  - The use of time lines and life lines in work with chronically mentally ill
      people.
AB  - This article describes the use of two treatment tools, time lines and life lines,
      designed to be used with adults who have had lifelong experience with severe and
      persistent mental illness. The premise of work with these clients is that their
      developmental stages and tasks have been skewed by years of mental illness. By
      graphically charting their reminiscence of life events, many clients can be
      helped to integrate into society and to resolve negative life experiences.
      Examples are given for the use of these tools with clients and with family
      members.

PMID- 2001847
TI  - Taking responsibility.

PMID- 2001848
TI  - Integrating case management and psychiatric hospitalization.
AB  - Although case management programs attempt to reduce the use of psychiatric
      hospitalization for clients with long-term mental illness, inpatient treatment
      still is required for many individuals in even the best community support
      systems. Even when formal mechanisms for hospital-community liaison exist, there
      often is little effective collaboration between hospital and community treatment
      staffs. Depleted from struggling with relapsing patients, case managers often
      discontinue their efforts during hospitalization. At the same time, hospital
      staff often demonstrate little interest in community caregivers until discharge
      planning begins in earnest. Hospital staff and case managers have common barriers
      to effective collaboration, but they can work together toward the goal of
      achieving maximum benefit from hospitalization within the context of a long-term
      community plan.

PMID- 2001849
TI  - They tried reality therapy, but he froze in a cave: curriculum deficits.
AB  - Social workers increasingly are called on to work with mentally ill people, but
      in most cases they are not trained to do so. There is a significant lag between
      what researchers have found, particularly in the biological fields, and what
      educators teach in social work schools. This article describes curriculum
      deficits in teaching about mental illness and the devastating consequences of
      those deficits. It then outlines a suggested curriculum and appropriate teaching
      methods. Social workers are called to take the lead in curriculum reform; when
      they do, students will follow.

PMID- 2001850
TI  - The treatment of childhood sexual trauma in chronically mentally ill adults.
AB  - Mental health treatment providers are becoming increasingly aware of the negative
      effects of childhood sexual abuse. Recent research has revealed that many adult
      psychiatric patients are victims of childhood sexual abuse and that their
      symptoms are directly related to that abuse. This article describes a treatment
      approach that provides intensive group therapy in a case management setting for
      chronically mentally ill adult women who are survivors of childhood sexual
      trauma.

PMID- 2001852
TI  - More assistance.

PMID- 2001853
TI  - Collaborating with families.

PMID- 2001851
TI  - Case management with homeless mentally ill people.
AB  - This article reports the findings of a National Institute of Mental Health (NIMH)
      services demonstration project that used a mobile case management team to serve
      homeless mentally ill clients. The project examined three issues: (1) factors
      associated with client engagement in case management, (2) clients' perceptions of
      how case management affected their quality of life, and (3) significant
      differences between clients who remained engaged in case management services and
      those who discontinued involvement. The results indicated that clients who
      received more frequent case management contact, had higher assessed independent
      living skills, were older, were less likely to be substance abusers, and had
      experienced fewer periods of homelessness and fewer prior psychiatric
      hospitalizations were more likely to remain engaged in case management services.
      After six months of case management, clients perceived significant improvement in
      their global well-being, living situation, use of leisure time, finances, and
      physical health. Implications for providing case management services to homeless
      mentally ill people are presented.

PMID- 2001854
TI  - Therapeutic nurseries.

PMID- 2001855
TI  - Chronic mental illness.

PMID- 2001856
TI  - Mission of the short-stay inpatient unit with chronic patients.

PMID- 2001857
TI  - Hospitals with the best information systems. 1991 SDR awards of excellence.

PMID- 2001858
TI  - Telephone health information services are popular.
AB  - U.S. households make more than 1 million calls per month to telephone health care
      information services, reports Inforum Inc., a Nashville, TN-based health care
      planning and marketing information company. In fact, more than 7 percent have
      used some form of telephone health care information service at least once during
      the past two years.

PMID- 2001859
TI  - Proactive executives: prospering in tough times.
AB  - Smart hospitals are not only surviving the current recession, some are even
      thriving. While economic slumps lead many executives to batten down the hatches
      and shift into a defensive management mode, experts say the real solution for
      hospitals lies in innovative, proactive management. In the economically battered
      Northeast, this strategy is working well for a pediatric hospital in Philadelphia
      and a large New York City medical center. But it's also working at a broad range
      of hospitals across the country. What do these very diverse institutions have in
      common? While each is moving forward to develop strategies and programs suited to
      its circumstances, all eschew the bunker mentality that comes to mind in tough
      times. In the words of one CEO, "You go out, decide what has to happen, and then
      make it happen--despite the fact that there are 8,000 reasons why it shouldn't
      happen."

PMID- 2001860
TI  - Medicare appeals process offers hope for some hospitals.
AB  - For hospital officials who feel wronged by Medicare's payment system, a recent
      opportunity to appeal geographic status has stirred new hope for survival. Last
      September, the Health Care Financing Administration published interim final
      regulations detailing criteria hospitals have to meet to merit reclassification;
      hospitals had until Nov. 6, 1990, to file their appears. Now, officials are
      slogging through nearly 1,000 completed applications. "There has been pent-up
      demand for some review" of geographic classification, says one official.

PMID- 2001861
TI  - Survey: pay raises growing for ambulatory care executives.
AB  - A new survey by the American Hospital Association finds ambulatory care
      professionals earning higher pay raises than they did three years ago. Among the
      factors in ambulatory care professionals' raises: the sizes of the budgets for
      which they are responsible, their job titles and their academic training.

PMID- 2001862
TI  - Informed consent problems become more complicated.
AB  - The advance of medical technology and heightened consumer awareness among
      patients are fueling a rise in some kinds of informed consent claims. Although
      these claims still make up a small percentage of the total, experts say
      plaintiffs' victories in two important California cases last year highlight
      problems in this area. The bottom line? "Judges are...a little bit more willing
      to hear the plaintiff's side," says one expert.

PMID- 2001863
TI  - Hospital CEOs divided on use of economic credentialing.
AB  - A small number of hospitals are looking at physicians' economic practice patterns
      in a credentialing context. Proponents say these programs are improving
      physicians' hospital practice performance.

PMID- 2001864
TI  - CEOs: decline in stays for births will bottom out.

PMID- 2001865
TI  - Mobile cath: shared risks and shared rewards.

PMID- 2001866
TI  - Outsourcing IS may help reduce headaches.

PMID- 2001867
TI  - Lawmakers' agenda for Medicare remains unclear.

PMID- 2001868
TI  - Patient transfer amendments refine HCFA policy.

PMID- 2001869
TI  - Ambulatory care professionals need to be 'well informed, creative and flexible'.

PMID- 2001870
TI  - Promoting good health is a key part of our job.

PMID- 2001871
TI  - Nasal biopsy in Wegener's granulomatosis.

PMID- 2001872
TI  - A post-sophomore summer fellowship program in community pathology.

PMID- 2001873
TI  - Diagnostic usefulness of nasal biopsy in Wegener's granulomatosis.
AB  - Wegener's granulomatosis (WG) frequently involves the upper respiratory tract,
      and nasal mucosal biopsy is often initially used to establish the diagnosis. To
      evaluate the diagnostic efficacy of nasal biopsy in WG, we reviewed the
      pathologic features of 30 such biopsy specimens from 17 patients with well
      documented WG. Active vasculitis (granulomatous or nongranulomatous) was
      identified in seven of the patients (41%). The presence of extravascular foci of
      necrosis in lung biopsy samples has recently received attention as a
      characteristic feature of WG. Similar foci were found in the nasal samples from
      six of our patients, although vasculitis was absent in the samples from two of
      them. If extravascular foci of necrosis are regarded as characteristic or even
      diagnostic of WG, two additional patients in our series could be regarded as
      having had diagnostic nasal biopsies (nine of 17 patients). Nasal biopsy could
      thus be considered as diagnostic in 53% of the patients. Samples larger than 5 mm
      in greatest dimension were more likely to contain diagnostic features than were
      smaller samples (P = 0.002).

PMID- 2001874
TI  - Adenocarcinoma of the stomach with invasion limited to the muscularis propria.
AB  - Adenocarcinoma of the stomach having invasion limited to the muscularis propria
      with or without lymph node metastasis, termed PM (proper muscle) gastric cancer
      by Japanese investigators, has a prognosis superior to that of carcinoma
      extending to the serosa and approaching that of early gastric cancer in Japan. To
      evaluate the occurrence and significance of PM gastric cancer in the United
      States, we analyzed 272 gastric carcinomas resected at our institution between
      1964 and 1983. Forty-two PM cancers (15%) were identified. Improved 5-year
      survival rate was noted for PM cancer when compared with survival rate for 215
      neoplasms exhibiting serosal invasion (29% versus 7%, P less than 0.001). In
      univariate analysis, a survival advantage was also associated with absence of
      lymph node metastasis, intestinal-type histopathology of the Lauren
      classification, the expanding pattern of the Ming classification, and polypoid or
      fungating gross configuration of tumor. In multivariate analysis, depth of tumor
      invasion remained significantly associated with improved 5-year survival rate
      independently of other variables, including lymph node metastasis. Using
      continuous survival curves, the prognostic significance of PM cancer prevailed
      throughout the 5-year postgastrectomy interval. Our data indicate that PM gastric
      cancer occurs in the United States and need not be considered "advanced" gastric
      carcinoma; depth of tumor invasion should be recognized as a nodal metastasis
      independent prognosticator of gastric cancer survival.

PMID- 2001875
TI  - Expression of blood group-related antigens and Helix pomatia agglutinin in
      malignant pleural mesothelioma and pulmonary adenocarcinoma.
AB  - In an attempt to differentiate malignant pleural mesothelioma from pulmonary
      adenocarcinoma by histochemical and immunohistochemical means, the glycoconjugate
      profiles of five reactive mesothelial lesions, 29 mesotheliomas (20 epithelial,
      three biphasic, and six fibrous types), and 38 well-differentiated pulmonary
      adenocarcinomas (34 papillary, two tubular, and two bronchioloalveolar types)
      were tested with ABH blood group-related antigens (BGR-Ag) antibody and Helix
      pomatia agglutinin (HPA) which agglutinates human type A erythrocytes. Formalin
      fixed, paraffin-embedded sections were stained by the avidin-biotin-peroxidase
      complex method. Reactive mesothelial lesions and malignant mesothelioma of the
      pleura were not stainable with BGR-Ag antibody or HPA, irrespective of the blood
      group type. In pulmonary adenocarcinoma, however, the test with BGR-Ag antibody
      showed a high positive rate with the compatible blood group type, especially in
      type O cases (83%). Using HPA, reactions of adenocarcinoma with types A and AB
      also demonstrated high positive results (94% and 100%, respectively), but even
      with types B and O positive reactions occurred in 80% and 33% of cases,
      respectively. The findings suggest that positive reactions with either BGR-Ag
      antibody or HPA can be indicative of pulmonary adenocarcinoma.

PMID- 2001876
TI  - Absence of normal-appearing proximal tubules in the fetal and neonatal kidney:
      prevalence and significance.
AB  - Rare fetuses and neonates with kidneys lacking normal-appearing proximal tubules
      have been described. In order to ascertain the prevalence of this histologic
      finding, and to study its associated clinicopathologic features, 500 consecutive
      perinatal autopsies (performed from 1981 to 1985) were reviewed. Kidneys lacking
      normal-appearing proximal tubules were found in six of 500 (1.2%) perinatal
      autopsies (one liveborn and five stillborn cases). The liveborn infant was one of
      a sibship with renal tubular dysgenesis. Four of the stillborn fetuses were
      derived from monochorionic twin gestations; the histologic abnormality was
      present in only one fetus from each twin pair. Three of the four twin pairs had
      pathologic features suggestive of twin-to-twin transfusion, with the renal
      abnormality present in the donor twin; renal hypoplasia existed in two instances.
      The fourth affected twin was a stillborn acardiac fetus with multiple congenital
      anomalies and unilateral renal agenesis. The fifth stillborn was a hydropic fetus
      with trisomy 21 and renal hypoplasia. In this series, lack of recognizable renal
      proximal tubules most often was not a manifestation of renal tubular dysgenesis.
      The histologic finding was associated with stillborn, renal hypoplasia, and
      congenital anomalies, and was strongly associated with monochorionic twinning (P
      = 0.001). In the stillborn cases in this series, we suggest that this finding may
      represent renal tubular degeneration resulting from renal hypoperfusion.

PMID- 2001877
TI  - Cellular response of the evolving myocardial infarction after therapeutic
      coronary artery reperfusion.
AB  - This study describes the cellular response of the evolving myocardial infarction
      in humans after early coronary artery reperfusion by one or more of the following
      therapies: streptokinase, percutaneous transluminal coronary angioplasty, tissue
      plasminogen activator, and/or coronary artery bypass graft surgery. Postmortem
      histologic changes were compared in two groups (n = 43 pairs) of human hearts
      with acute myocardial infarction matched for clinical age and left ventricular
      location of the infarct. The treatment group received one or more of the forms of
      reperfusion therapy. The control group received conventional therapy. The
      treatment group was judged to have an older histologic age infarct, P less than
      0.002, compared with documented clinical age. For example, infarcts that were
      clinically 4 days old or less were judged histologically to be 1 day older. The
      treatment group had a higher Cellular Response Index, P less than 0.017; more
      hemorrhage within the infarct, P less than 0.001; a greater extent of selective
      myocardial cell necrosis, and a lesser extent of coagulation necrosis, P less
      than 0.05; more patchy, nontransmural distribution of necrosis, P less than 0.04;
      and a more florid cellular response, specifically more macrophages, P less than
      0.034, and reactive stromal cells, P less than 0.05. In infarcts less than 3 days
      old clinically, the treatment group had hemorrhage and a cellular response which
      were wide-spread throughout the lesion, P less than 0.05, n = 18 pairs. In
      infarcts 3 to 4 days old clinically, the treatment group had a florid cellular
      response due to more macrophages, P less than 0.05, n = 9 pairs. In infarcts 5 to
      10 days old, the treatment group had more macrophages, P less than 0.01; and more
      phagocytosis, P less than 0.003. In infarcts 10 to 40 days old clinically, the
      treatment group had scar formation that was patchy, P less than 0.05. In
      conclusion, this study demonstrates that early therapeutic coronary artery
      reperfusion after an acute myocardial infarction alters the pattern of injury and
      the cellular response to the evolving myocardial infarction so that the classical
      criteria for infarcts need to be modified.

PMID- 2001878
TI  - Lipoblastic meningioma: "vacuolated meningioma".
AB  - This report describes and illustrates seven cases of benign meningeal tumors,
      including one in the retro-bulbar region of the orbit, which were characterized
      by vacuolated signet-ring cells. Occasional typical meningothelial areas were
      also seen; however, the signet-ring cells were the dominant feature. The vacuoles
      were consistently negative with the various stains for mucin. In one single case
      in which nonparaffin-embedded tissue was still available, the vacuoles were
      positive for fat stains. Immunohistochemical stains done in three of the cases
      showed that the tumor cells were positive for vimentin. S-100 protein was
      definitely positive in two cases and weakly positive in one. One of the three
      cases was positive for cytokeratin and another was positive for epithelial
      membrane antigen. The name "lipoblastic meningioma" appears to be acceptable as a
      descriptive term, since these tumors are, in our opinion, of definite meningeal
      origin, probably representing a predominantly mesenchymal (lipocytic)
      differentiation of the arachnoidal cells. This term, however, does not imply a
      clinical behavior analogous to that of true liposarcoma. In fact, these tumors
      have consistently behaved as benign local problems, analogous to the biologic
      course of ordinary meningioma.

PMID- 2001879
TI  - Stereology, flow cytometry, and immunohistochemistry of follicular neoplasms of
      the thyroid gland.
AB  - A retrospective analysis of surgically resected thyroid cold solitary nodules was
      performed by stereology, DNA flow cytometry, and immunohistochemistry in 15
      follicular adenomas and 15 well-differentiated follicular carcinomas to determine
      if a differential diagnosis of both follicular neoplasms can be done exclusively
      from cytologic criteria. Between 150 and 200 tumor cell nuclei (TCN) were studied
      per case for their TCN profile area, perimeter, and density, as well as for
      stereologic estimates, including the new parameter, volume-weighted mean particle
      volume (Vv). Flow-cytometric analyses included measurement of the DNA index and
      the percentage of cells in S phase and G2M phase. The same tumors were examined
      for the expression of thyroglobulin and the intermediate filaments vimentin and
      keratin. Follicular adenomas and follicular carcinomas did not show any
      significant differences in stereologic estimates related to TCN size. Both groups
      included similar proportions of diploid and aneuploid neoplasms. Aneuploid
      follicular neoplasms showed a significantly greater area, perimeter, and volume
      of TCN as compared with diploid tumors, regardless of their histologic diagnosis.
      Follicular adenomas and follicular carcinomas expressed a similar staining
      pattern for the tested immunoreagents, with a few cases coexpressing vimentin and
      keratin. From our results, a differential diagnosis of follicular neoplasms
      cannot be performed on the basis of cytologic aspirates exclusively. Infiltration
      of capsula or vessels remains the only safe indicator of malignancy in the
      absence of metastases. The lack of cytologic differences suggests that some
      follicular adenomas are preinvasive carcinomas, not yet showing infiltrative
      growth at the time of resection.

PMID- 2001880
TI  - Pulmonary mucinous cystic tumors of borderline malignancy.
AB  - Mucus-filled cystic tumors of low or borderline malignant potential, well
      recognized in ovary and appendix, have received little attention in the lung. We
      present data on 11 patients, all of whom had solitary pulmonary nodules resected
      in which mucus was the major histologic component. Prognosis appears good; no
      patient had developed local recurrence or metastatic spread of tumor (follow-up,
      1 to 9.5 years; mean, 4.7 years). Columnar mucus-producing cells lined the cysts
      in all cases, with cytologic and architectural atypia varying from minimal to
      microscopic foci of carcinoma; paucicellular mucus dissection into surrounding
      lung analogous to pseudomyxoma peritonei was seen in seven cases. The histologic
      and clinical findings are consistent with a mucinous cystic tumor of low or
      borderline malignant potential.

PMID- 2001881
TI  - Quantitative nuclear cell image analyses of thyroid tumors from archival
      material.
AB  - Sixty-three sections of Feulgen-stained thyroid cell nuclei from paraffin
      embedded material, including five multinodular goiters, 10 adenomas, 36 papillary
      carcinomas, seven follicular carcinomas, and five medullary carcinomas were
      analyzed by means of the SAMBA 200 (TITN, Grenoble, France) cell image processor.
      This was done in order to obtain nuclear characteristics of papillary versus
      follicular carcinomas. The nuclear features were assessed by morphometric,
      densitometric, and textural parameters. Our preliminary results indicate that the
      cell nuclei from typical histopathologic specimens of follicular thyroid cancers
      belong to a larger thyroid cell nuclei population corresponding to the
      histopathologic family of papillary thyroid cancers. This follicular neoplastic
      cell nuclei population appears to be quite distinct from the typical medullary
      neoplastic cell nuclei population which also belongs to the papillary neoplastic
      cell nuclei population. It appears that there is a specific papillary cell nuclei
      subpopulation containing typical hypochromatic cell nuclei. We also observed a
      dramatic increase in nuclear size and hyperchromatism between normal
      (multinodular goiters) and neoplastic (carcinomas) thyroid tissues, with the
      benign tissues (adenomas) showing intermediate nuclear characteristics.

PMID- 2001882
TI  - Systemic occlusive arteriopathy with sudden death in a 10-year-old boy.
AB  - A 10-year-old boy died suddenly while playing. Autopsy examination disclosed an
      extensive occlusive arteriopathy involving all major epicardial coronary
      arteries, with associated remote myocardial infarct. Also affected were the renal
      arteries and a branch of a pulmonary artery. The process was characterized by
      concentric intimal hyperplasia, focally replacing the media, with disruption of
      elastic laminae in more advanced lesions. The proliferating cells had
      ultrastructural features of smooth muscle cells. There was no evidence of
      atherosclerosis or vasculitis. While the case shares some features with known
      arteriopathies, this constellation of clinical and pathologic findings appears to
      be unique.

PMID- 2001883
TI  - Intravascular malignant lymphomatosis: a case of T-cell lymphoma probably
      associated with human T-cell lymphotropic virus.
AB  - Intravascular malignant lymphomatosis (IML) is an unusual condition characterized
      by proliferation of lymphoma cells exclusively within the blood vessels. Most of
      the cases reported are of B-cell origin. We report a rare case of T-cell IML
      probably associated with human T-lymphotropic virus (HTLV-1) infection. The
      present case suggests that T-cell lymphoma and HTLV-1-associated lymphoma
      occasionally represent a form of intravascular proliferation.

PMID- 2001884
TI  - 11 steps to waste management.

PMID- 2001885
TI  - Implants: hygiene maintenance of dental implants.

PMID- 2001886
TI  - [Osseointegration. Current concepts in oral implantology practice].

PMID- 2001887
TI  - [Esthetics and osseointegration, unit prosthesis on an IMZ implant].

PMID- 2001888
TI  - [Gingival graft].

PMID- 2001889
TI  - [Reinclusion of deciduous teeth].

PMID- 2001890
TI  - [Automated treatment of dental radiographic films].

PMID- 2001891
TI  - [1st barometer on dentists and communication].

PMID- 2001892
TI  - [Early detection of oral epidermoid carcinomas during dental treatment].

PMID- 2001893
TI  - [Treatment of mandibular luxation. Observation no. 25 of the Edwin Smith surgical
      papyrus: examination--diagnosis].

PMID- 2001894
TI  - The use of a multimodal image, the apple technique, to facilitate clinical
      hypnosis: a brief communication.
AB  - A 1- to 3-minute exercise involving imagination (of an apple) and ideomotor
      ideation (hand levitation) is a simple, benign technique that is useful for
      illustrating to patients the nature of imagery and hypnosis. It avoids power
      struggles and allows a reasonable approximation of the patient's capacity for
      imagery and hypnotic responsiveness, without emphasizing the use of a hypnotic
      procedure. When administered to 35 college students, the hand levitation
      component of this exercise correlated with the Stanford Hypnotic Susceptibility
      Scale, Form C (Weitzenhoffer & E. R. Hilgard, 1963) (r = .66, p less than .001)
      and with the Stanford Hypnotic Clinical Scale: Adult (Morgan & J. R. Hilgard,
      1975, 1978/79) (r = .60, p less than .001).

PMID- 2001895
TI  - Durability of "posthypnotic suggestions" as a function of type of suggestion and
      trance depth.
AB  - 3 types of "posthypnotic suggestion," based upon factor analytic studies, were
      administered to high hypnotizable Ss (reals) and to low hypnotizable Ss
      instructed to simulate hypnosis (simulators) (N = 12 high and 6 low hypnotizable
      Ss per suggestion). The "posthypnotic suggestions" consisted of instructions
      given to Ss following a hypnotic induction that, when the posthypnotic cue was
      later given, they would re-enter the hypnotic state and perform a certain task at
      that time. Ss were then tested 6 times for durability of "posthypnotic response"
      during an 8-week period. Responses to the "suggestions" were rated by research
      assistants (objective scores) and by Ss themselves (subjective scores). There was
      a significant Trials x Type of "Suggestion" interaction for both types of scores
      for the reals but not for the simulators, indicating different rates of decline
      with time for the different "suggestions" for the hypnotic Ss. Depth of reported
      hypnotic trance during the assessment sessions was found to be strongly related
      to performance of the "posthypnotic suggestion" for both real and simulating Ss.

PMID- 2001896
TI  - The relationship between absorption, openness to experience, anhedonia, and
      susceptibility.
AB  - Examination of the absorption (Tellegen Absorption Scale [TAS] of Tellegen &
      Atkinson, 1974), openness to experience (OTE Inventory of Costa & McCrae, 1978),
      and anhedonia (ANH Scales of L. J. Chapman, J.P. Chapman, & Raulin, 1976) scales
      suggested that they might be conceptually related. Given the reliable
      relationship between TAS and hypnotic susceptibility, the authors were interested
      in studying OTE and ANH as possible personality correlates of hypnotic
      susceptibility. 2 studies, 1 involving a community sample and the other a sample
      of university students, were conducted to assess the relationships between the
      TAS, OTE, and ANH scales and hypnotic susceptibility. As predicted, in Study 1
      (community sample) the TAS and OTE inventories were positively correlated with
      one another and both were negatively correlated with the ANH scale. This pattern
      of correlations was replicated in Study 2 (university sample), but only TAS
      correlated significantly with hypnotic susceptibility. Factor analyses further
      confirmed these findings. It was concluded that the conceptual relationship among
      the TAS and the OTE and ANH scales resides in some dimension other than hypnotic
      susceptibility.

PMID- 2001897
TI  - Krill enzymes. A new concept for efficient debridement of necrotic ulcers.

PMID- 2001898
TI  - Disseminated histoplasmosis presenting as an ulcerated verrucous plaque in a
      human immunodeficiency virus-infected man. Report of a case possibly involving
      human-to-human transmission of histoplasmosis.
AB  - A 46-year-old homosexual man with disseminated histoplasmosis and human
      immunodeficiency virus (HIV) infection had a histoplasmosis-related ulcerated
      verrucous plaque above his left upper lip; systemic and cutaneous disease
      manifestations of histoplasmosis resolved with daily ketoconazole therapy.
      Disseminated histoplasmosis, with similar cutaneous features, also was present in
      his HIV-seropositive male sexual partner. The possibility of human-to-human
      transmission of histoplasmosis between these patients is considered and the skin
      lesions of systemic fungal infections in HIV-infected patients are reviewed.

PMID- 2001899
TI  - Kaposi sarcoma associated with human immunodeficiency virus infection.
AB  - In the present study, 11 patients with epidemic Kaposi sarcoma were evaluated;
      55% were in stage IV and 45% in stage II; in addition, 75% had systemic symptoms,
      89% had low total and T-lymphocyte counts, and all of them had not only low T
      helper lymphocyte counts but also T-helper/T-suppressor ratios. The majority of
      patients (89%) had low proliferative responses with phytohemagglutinin (PHA).
      Nine patients were treated with: alpha-2 interferon (five patients), zidovudine
      (two patients), doxorubicin and zidovudine (one patient), and radiotherapy (one
      patient). There were only five patients with stable disease, three treated with
      alpha-2 interferon, one with doxorubicin, and one with doxorubicin plus
      azidothymidine. Two patients (one with doxorubicin and one with doxorubicin plus
      zidovudine) needed lithium to increase leukocyte and platelet counts. In May
      1989, 73% of patients were dead (median survival 8 +/- 2 months). It is concluded
      that: (1) it is important to select the patients who have the best chance to
      improve with treatment; (2) the response with alpha-2 interferon or
      monochemotherapy is low and there is no change in overall survival; (3) a low
      helper cell count, low T-helper/T-suppressor ratio, and low proliferative
      response with mitogens are features of poor prognosis; (4) toxicity with
      treatment was acceptable; and (5) lithium increased neutrophil and platelet
      counts.

PMID- 2001900
TI  - Genetically determined coincidence of Kaposi sarcoma and psoriasis in an HIV
      negative patient after prednisolone treatment. Spontaneous regression 8 months
      after discontinuing therapy.
AB  - We report the case of drug-induced, acrolocalized Kaposi sarcoma (KS), arising
      multicentrically in both palms and soles of a male patient who has had widespread
      psoriasis since 12 years of age. This 59-year-old man, of Mediterranean origin,
      was HIV antibody-negative and had received oral prednisolone treatment over 5
      months for chronic obstructive lung disease (initial dose: 75 mg/d). Eight months
      after discontinuing oral treatment the KS nodules regressed spontaneously and
      finally disappeared completely without additional treatment. Light and electron
      microscopic investigations confirmed the diagnosis of KS, whereas laboratory
      tests excluded HIV infection and suggested mild immune dysfunction. The existence
      of HLA loci predisposing to KS and to psoriasis (A1, DR5, DR7, DR11) was
      characteristic for the simultaneous occurrence of these two diseases. This case
      report demonstrates the complex interrelationships between genetic
      predisposition, drugs leading to immune suppression, and the evolution of an
      unusual neoplasm.

PMID- 2001901
TI  - The incidence of skin diseases in Abu Dhabi (United Arab Emirates).
AB  - This is the first report on the incidence of skin diseases in the United Arab
      Emirates. A diagnostic analysis of 26,670 patients seen over the last 2 years
      (January 1987 to December 1988) at the Dermatology Clinic in Mafraq Hospital, Abu
      Dhabi, UAE, is presented. The skin diseases have been listed in order of
      frequency and their percentages are compared with figures from other parts of the
      world. The common skin diseases as well as the peculiarities are discussed.

PMID- 2001902
TI  - Leprosy in Qatar.
AB  - Clinical and histopathologic features of 104 cases of leprosy diagnosed between
      1982 and 1989 in the State of Qatar were studied. There were 88 male (84.6%) and
      16 (15.4%) female patients aged 18 to 64 years. Eighty-four of the cases were
      diagnosed during the initial mandatory medical screening on arrival to Qatar.
      Almost all (103) were expatriates and only one 50-year-old woman was a Qatari.
      Indians formed the largest group (60.6%), followed by Bangladeshi (6.7%),
      Pakistani (5.8%), and others. The majority of cases were classified as
      lepromatous (43.3%) or tuberculoid (43.3%). Although Qatar is a relatively
      leprosy-free country, the influx of a large number of workers from developing
      countries seeking employment forms a potential public health hazard.

PMID- 2001903
TI  - Tinea capitis in the United Arab Emirates.
AB  - The authors reviewed the causative agents for tinea capitis in United Arab
      Emirates nationals attending Tawam Hospital, Al Ain, between 1981 and 1988.
      Microsporum canis was the most prevalent organism isolated. Oral griseofulvin
      remained the treatment of choice. The addition of isotretinoin appeared promising
      in the chronic inflammatory forms.

PMID- 2001904
TI  - The black disease of Arabia, Sowda-onchocerciasis. New findings.
AB  - Sowda, the localized asymmetrical lesion of onchocerciasis endemic in Yemen and
      Southern Saudi Arabia, is characterized by hyperpigmented lichenified papular
      lesions on one leg with intense pruritus. There is enlargement of femoral and
      inguinal lymph glands. In our study, even the long standing cases do not show
      elephantiasis of the leg or genitalia. Microfilaria appeared to be scarce and
      adult worms could not be detected clinically, as well as by ultrasonography
      (except in one case). There was no significant lymphatic obstruction; such cases
      were studied by contrast lymphangiography and isotope lymphangiography.

PMID- 2001905
TI  - Kaposi sarcoma in a kidney transplant patient.

PMID- 2001906
TI  - Treatment of pemphigus.
AB  - Ninety-eight cases of various types of pemphigus were treated between 1978-1987.
      Sixty-one cases were pemphigus vulgaris (PV), 22 cases were pemphigus foliaceus,
      generalized type (PFG) in which one case developed pemphigus vegetans, 11 cases
      were pemphigus foliaceus localized type (PFL), and four cases were pemphigus
      erythematosus (PE). Fifteen mild cases of PV and three mild PFG were treated with
      corticosteroid (prednisolone or prednisone) alone, and dapsone or
      cyclophosphamide (CP) were added as treatment failed in two cases of each.
      Dapsone alone was used effectively in three cases of mild PV. Eight cases of
      moderate and three cases of severe PV, as well as five cases of moderate PFG,
      failed to respond to corticosteroid alone but were cleared by the addition of CP.
      Thirty-two moderate cases of PV and PFG treated with a combination of
      corticosteroid 60 mg/day plus initial CP and 14 severe cases of PV and PFG
      treated with corticosteroid 120 mg/day plus initial CP, resulted in clearing skin
      lesions in 2 months. Azathioprine or chlorambucil were substituted in three cases
      who developed CP toxicity. Addition of gold sodiumthiomalate in six refractory
      cases when the above regimens failed, caused a complete remission in two and
      partial control in four. Higher dosage of prednisolone or prednisone more than
      120 mg/day has never been used. Eleven cases of PFL and four cases of PE were
      treated with uneventfully good results. Intercellular antibody titers became
      negative within 4.67 months except in refractory cases, however, the treatment
      was continued for at least 3 years. Herpes simplex superimposed infection was
      more common than herpes zoster infection.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2001907
TI  - Cutaneous local necrosis following interferon injections.

PMID- 2001909
TI  - Advertising, pharmaceutical industry, and dermatology.

PMID- 2001908
TI  - Cutaneous problems with drug therapy in rheumatoid arthritis.

PMID- 2001910
TI  - Successful treatment of generalized pustular psoriasis with clofazimine.

PMID- 2001911
TI  - Endemic treponematoses. Part I. Yaws.

PMID- 2001912
TI  - Characterization and physiological role of epidermal lipids.

PMID- 2001913
TI  - The epidermal nevus syndrome.

PMID- 2001914
TI  - The resurgence of yaws. World-wide consequences.

PMID- 2001915
TI  - Comparative biochemistry and biophysics of ribosomal proteins.

PMID- 2001916
TI  - Aging and immune function.
AB  - Since it is too difficult to study aging of the organism as a whole, most
      investigators try to focus on a specific physiological system that exhibits age
      dependent functional changes, in the hopes that elucidation (in biochemical and
      developmental terms) of the mechanism of senescent change will provide insight
      into the aging process itself. The immune system is among the most maleable of
      such models, in that well-defined cell types will produce well-defined molecules
      with predictable functions in vitro and in vivo. The increasing power of basic
      immunological science should, in the next decade, permit an increasingly fine
      appreciation of how aging leads to immune decline. This expanding conceptual
      framework will then suggest new ideas about the role of immunosenescence in
      degenerative, infectious, and neoplastic illnesses and may also generate
      increasingly rational strategies for therapeutic intervention.

PMID- 2001917
TI  - Molecular structure and function of microtubule-associated proteins.

PMID- 2001918
TI  - Development of follicles in the mammalian ovary.

PMID- 2001919
TI  - On presentation of the Proctor medal of the Association for Research in Vision
      and Ophthalmology to Dr. Hans Bloemendal.

PMID- 2001920
TI  - Proctor lecture. Disorganization of membranes and abnormal intermediate filament
      assembly lead to cataract.

PMID- 2001921
TI  - Introduction of Frank Werblin, Friedenwald Award winner, 1990.

PMID- 2001922
TI  - Synaptic connections, receptive fields, and patterns of activity in the tiger
      salamander retina. A simulation of patterns of activity formed at each cellular
      level from photoreceptors to ganglion cells [the Friendenwald lecture].

PMID- 2001923
TI  - Retinal ganglion cell loss is size dependent in experimental glaucoma.
AB  - Thirty-two areas located in the temporal midperipheral retina were evaluated in
      whole-mount preparations from four monkeys with monocular experimental glaucoma.
      Diameter frequency distributions of remaining ganglion cells in the glaucomatous
      eye were compared with corresponding areas in the normal fellow eye. Large cells
      were significantly more vulnerable at each stage of cell damage as determined by
      linear-regression analysis. The magnitude of size-dependent loss was moderate at
      an early stage (20% loss), peaked at 50% total cell loss, and decreased in
      advanced damage (70% loss). In glaucomatous eyes, the lower retina had
      significantly more large cell loss than the corresponding areas of the upper
      retina. In optic nerve zones that matched the retinal areas studied, large axons
      selectively were damaged first. Psychophysical testing aimed at functions
      subserved by larger ganglion cells is recommended for detection and follow-up of
      early glaucoma; however, assessment of functions unique to small cells is more
      appropriate for detecting change in advanced glaucoma.

PMID- 2001924
TI  - Endogenous hormonal changes and circadian elevation of intraocular pressure.
AB  - A unique circadian rhythm of intraocular pressure (IOP) occurs in laboratory
      rabbits housed in a light-dark environment. The IOP is low in the light and high
      in the dark. In 32 rabbits studied, the IOP was 18.7 +/- 0.3 mm Hg (mean +/- the
      standard error of the mean) at 2 hr before the onset of dark and 24.9 +/- 0.6 mm
      Hg at 2 hr into the dark. The changes in endogenous hormones corresponding to
      this elevation of IOP were studied. Concentrations of norepinephrine (NE),
      epinephrine (Epi), corticosterone, and melatonin in the plasma and NE and
      melatonin in the aqueous humor were determined. Changes in plasma catecholamines
      were variable and statistically insignificant. A decrease of plasma
      corticosterone and an increase of plasma melatonin in the dark were observed.
      Norepinephrine and melatonin levels in the aqueous humor increased in the dark.
      In ten rabbits with unilateral transection of the cervical sympathetic trunk, the
      elevation of IOP was absent only in the decentralized eye. The changes in plasma
      NE, Epi, and melatonin levels from the light to the dark phase were
      insignificant. The plasma corticosterone level decreased. In the dark phase,
      aqueous humor NE level in the decentralized eye was significantly lower than that
      in the intact eye. Melatonin levels in these two eyes were indifferent. In 22
      rabbits housed in a constant dark environment, aqueous humor NE concentration
      increased corresponding to the circadian elevation of IOP. The authors conclude
      that the activation of ocular sympathetic nerves is directly related to the
      circadian elevation of IOP.

PMID- 2001925
TI  - Anisocoria. Variation and clinical observation with different conditions of
      illumination and accommodation.
AB  - Variations in anisocoria in light and dark conditions are used to help diagnose
      normal and pathologic conditions; however, there have been few observations of
      anisocoria in different lighting and accommodative conditions. The authors
      measured pupil size photographically in a group of normal subjects examined in
      six conditions that were controlled for illumination and accommodation. Greater
      variation and average extent of anisocoria were found in conditions that resulted
      in larger pupil size. A subset of subjects repeated several sessions. For this
      group, the average value of anisocoria and variability tended to be greater in
      dark conditions. These results show that the observation of anisocoria varies
      under different conditions, and they suggest careful consideration of conditions
      used clinically to assess pupil equality. Our analysis shows that for a given
      observation threshold, conditions that produce even modest changes in variability
      can cause dramatic changes in the probability of observing anisocoria.

PMID- 2001926
TI  - Aqueous humor pilocarpine and timolol levels after instillation of the single
      drug or in combination.
AB  - Aqueous humor levels of pilocarpine and timolol in rabbits after administration
      of either 2% pilocarpine or 0.5% timolol in single-drug solutions were compared
      with the concentrations found after instillation of a fixed combination of 0.5%
      timolol and 2% pilocarpine drops. Time intervals considered were 15 min, 30 min,
      1 hr, 4 hr, and 8 hr after application. Drug concentrations were analyzed in
      individual aqueous samples by high-performance liquid chromatography. No
      statistically significant differences in either pilocarpine or timolol
      concentrations in aqueous humor were found at any time tested between the single
      drug preparations and the combination.

PMID- 2001927
TI  - A comparison of two photographic systems for grading cataract.
AB  - Two different systems for classifying lens opacities were compared: the Lens
      Opacity Classification System version II (LOCS II) and the system developed at
      Johns Hopkins University. Using the two systems, slit-lamp photographs of the
      nucleus and retroillumination lens photographs of 100 eyes were graded. Each
      photograph was graded independently by three trained observers, and the time
      taken to grade the photographs was similar. Each system uses photographs to
      define the severity of nuclear opacity and nuclear color, and each showed good
      interobserver agreement (kappa statistic, greater than 0.6). The method of
      classifying cortical and posterior subcapsular opacity varied, and although
      interobserver agreement was acceptable in each system, it was somewhat higher
      with the Hopkins system. Because different standards and definitions are used to
      define severity with each system, there was some variation in the classification
      of individual photographs and corresponding differences in the proportion of
      photographs in each grade of severity. These data provide a useful cross
      reference for future comparison of studies using these systems.

PMID- 2001928
TI  - Human crystalline lens phospholipid analysis with age.
AB  - Paired human crystalline lenses (n = 21, patient ages 20-79 years) were extracted
      for lipids with chloroform-methanol 2:1, using the Folch method. The extracted
      crude lipids were analyzed at 202.4 MHz by phosphorus-31 magnetic resonance
      spectroscopy (31P NMR). Fourteen membrane phospholipids were detected including
      phosphatidylcholine (PC), lysophosphatidylcholine (LPC), phosphatidylcholine
      plasmalogen (PC plas), phosphatidylethanolamine (PE), phosphatidylethanolamine
      plasmalogen, lysophosphatidylethanolamine (PA), phosphatidylglycerol (PG),
      lysophosphatidylglycerol, phosphatidylserine (PS), phosphatidic acid,
      phosphatidylinositol, sphingomyelin (SPH), and two uncharacterized phospholipids.
      The uncharacterized phospholipid at 0.13 was the predominant phospholipid,
      comprising 43.20% of the lens phospholipid profile. A decrease in mole percent of
      phosphorus concentrations of PE, PC plas, and PC and an increase in SPH
      correlated with age. The following computed indices decreased with age: PC/PG and
      PE/PS; PC + PE; (PC + PC plas); and PC/PS. The following computed indices
      increased with age: (PC + SPH)/(PE + PS), SPH/PG, (PC + SPH)/(PE + PS), LPC/PC,
      LPE/PE, SPH/PE, and SPH/PC. Changes in membrane phospholipids of the crystalline
      lens with age as detected by 31P NMR can be used to fingerprint lens maturation.

PMID- 2001929
TI  - Changes in lens membrane major intrinsic polypeptide during cataractogenesis in
      aged Hannover Wistar rats.
AB  - Cataracts previously have been shown to occur spontaneously in aged Hannover
      Wistar rats. The morphology and time course of opacification of these cataracts
      are very similar to those appearing in the human lens, where it has been
      previously shown that the major intrinsic polypeptide (MIP26K) of the fiber cell
      membrane undergoes covalent modification during cataractogenesis. To ascertain
      possible biochemical similarities between the two cataract systems, antisera were
      made against synthetic peptides corresponding to the sequence of MIP26K to probe
      Western blots of lens proteins from transparent versus opaque lenses from normal
      aged rats. The results of this analysis showed that these antisera can detect the
      presence of covalent changes occurring in the MIP26K molecule during the
      development of cortical opacities in the normal aged rat.

PMID- 2001930
TI  - The hydration of actin.
AB  - The hydration of actin was studied by differential scanning calorimetry between 
      30 degrees C and 30 degrees C and by thermogravimetric analysis. The differential
      scanning calorimetry provided the freezable water content of G- and F-actin as a
      function of concentration, and the thermogravimetric analysis measured the total
      water content. The difference between the two yielded the nonfreezable water
      content (bound water) as a function of concentration. The nonfreezable water
      content of G-actin was higher than the F-actin over the whole concentration range
      from 1-40% actin.

PMID- 2001931
TI  - Fixation characteristics in macular disease. Relationship between saccadic
      frequency, sequencing, and reading rate.
AB  - The relationship between reading rate and saccadic frequency in patients with
      macular degeneration was studied to determine if this simple measure of eye
      movements would be helpful in explaining the reduction in reading rates. Nineteen
      subjects and five controls were tested for visual acuity, reading rate, and
      saccadic frequency for intended stationary, simple left-to-right, and sequencing
      step tasks. Eye movements were recorded using an electro-oculography technique.
      Absolute eye position was not known. The results demonstrated that, using a 2
      degree threshold for a stationary target, patients refixated a mean of 42.7 times
      per min, and controls refixated 0.00 times per min. For a two-letter left-to
      right task, patients averaged 3.57 times more saccades than an ideal response,
      and controls had 1.14 times more saccades than ideal (P less than 0.01). For a
      five-letter left-to-right sequencing task, patients refixated a mean of 2.10
      times more than ideal, and controls refixated 1.15 times more than ideal (P less
      than 0.05). Regression analysis demonstrated that sequencing task scores of
      saccadic frequency and visual acuity were the best predictors of reading rate (r2
      = 0.705). These results indicate that higher saccadic frequencies are associated
      with lower reading rates and that there appears to be a relationship between the
      sequencing of visual information and reading rate.

PMID- 2001932
TI  - Temporal and spatial properties of suppressive rod-cone interaction.
AB  - Recordings were obtained from rods and horizontal cells of Xenopus, using an
      eyecup preparation. The enhancement of cone signals produced by rod backgrounds
      was measured using flickering red spots of varying intensity and diameter, and
      the experiments were repeated with cone stimuli consisting of alteration of
      wavelengths of 660 and 605 nm, adjusted for equal effects on rods or cones
      ("silent substitution"). Rods responded to red flicker with discrete wavelets up
      to 5 Hz. The characteristics of suppressive rod-cone interaction (SRCI) depend on
      the precise stimulus parameters. In particular, the reported low-pass attenuation
      of SRCI is absent with silent substitution. An analysis of the responses to
      backgrounds in horizontal cells, and the effects of the red light flashes in
      rods, led to the conclusion that the characteristics of SRCI are determined
      partially by the fact that "cone" stimuli excite rods and vice versa. This result
      simplifies the mechanism of SRCI and permits a comparison between the studies of
      SRCI using electroretinograms and horizontal cells.

PMID- 2001933
TI  - A 52 kD cytoskeletal protein from retinal rod photoreceptors is related to
      erythrocyte dematin.
AB  - A novel cytoskeletal antigen, RET52, has been identified in the mouse retina.
      This 52 kD polypeptide is antigenically related to dematin (band 4.9), an actin
      bundling phosphoprotein component of the erythrocyte membrane skeleton. Like
      dematin, RET52 is also a substrate for cAMP-dependent protein kinase. Within the
      retina, RET52 is primarily concentrated in two regions-the rod inner segment and
      the outer synaptic layers-although the developmental expression of RET52 differs
      in these areas. RET52 is present at birth in the inner segment, but appears about
      the time of initial synapse formation (postnatal day 4-6) in the outer plexiform
      layer. No differences in RET52 expression have been detected in early-stage mouse
      retinas with the retinal degeneration (rd) phenotype. RET52 localization,
      developmental expression, homologies to dematin, and in vitro phosphorylation
      pattern suggest a possible role for cytoskeleton-associated proteins in the
      initiation or control of disk membrane assembly and/or synapse formation in the
      rod photoreceptor.

PMID- 2001934
TI  - Quantification of stromal destruction in the inflamed cornea.
AB  - An intrastromal injection of endotoxin lipopolysaccharide (LPS) in one eye of New
      Zealand albino rabbits induced a prominent keratitis characterized clinically and
      microscopically by edema and infiltration. Polymorphonuclear leukocytes (PMNs)
      constituted the primary invading leukocytic element. Collagen synthesis was
      measured by pulsing the corneas with 3H-proline before inducing inflammation. The
      invasion of the cornea by leukocytes did not alter the conversion of proline to
      hydroxyproline significantly in the stroma during the 14-day observation period,
      signifying that there were only negligible changes in the rate of collagen
      synthesis. However, the percentage of total stromal protein represented by
      collagen (ie, collagen/total protein) was only 50% of that in comparable corneas
      receiving an injection of phosphate-buffered saline. Some animals were rendered
      leukopenic by intravenous nitrogen mustard before intrastromal LPS injection
      caused a less severe corneal inflammatory response, characterized microscopically
      by fewer infiltrating leukocytes. Similarly, in nonleukopenic rabbits, topical
      therapy with 1% prednisolone acetate markedly reduced the corneal inflammatory
      response which also was characterized by fewer invading leukocytes. In neither
      instance was there extreme collagen loss, suggesting that the loss of stromal
      collagen is related to PMN infiltration.

PMID- 2001935
TI  - Optical measurement of the axial eye length by laser Doppler interferometry.
AB  - A new technique has been developed to determine the axial length of the human eye
      in vivo. Based on laser interferometry in conjunction with the Doppler technique,
      it uses partially coherent light. This new technique complies with laser safety
      regulations. High accuracy is achieved, the optical length (OL) can be determined
      within +/- 30 microns, and the reproducibility of the geometric eye length is
      greater than +/- 25 microns. Possible errors are discussed. First comparisons
      with the ultrasound technique yield good agreement for emmetropic subjects and
      for subjects with a myopia of up to 10 diopters. The advantages of the laser
      doppler interferometry (LDI) technique are high accuracy, high transversal
      resolution, and more comfort for the patient (it is a noncontact method; no
      anesthesia is needed). Possible future applications of LDI, like measurements of
      fundus profiles and of retinal thickness, are mentioned.

PMID- 2001936
TI  - Membrane phospholipids of the ocular tunica fibrosa.
AB  - The authors compared porcine corneal and scleral membrane phospholipids
      determined with use of 31P nuclear magnetic resonance (NMR). These tissues make
      up the tunica fibrosa (outer coat) of the eye. Since the sclera, unlike the
      cornea, does not possess an epithelium or an endothelium, comparative analysis of
      these tissues included examination of the cornea with and without its epithelium
      and endothelium. The phospholipids quantified include: phosphatidylcholine,
      lysophosphatidylcholine, phosphatidylcholine plasmalogen,
      phosphatidylethanolamine, lysophosphatidylethanolamine, phosphatidylethanolamine
      plasmalogen, phosphatidylserine, sphingomyelin, phosphatidylinositol,
      phosphatidylglycerol, cardiolipin, and an uncharacterized phosphatide that
      accounts for 1.5%-3.5% of the detected phospholipids. Metabolic indices,
      comprised of individual or grouped metabolites, were calculated to further
      compare and contrast metabolites and to provide pathway-specific metabolic
      interrelations for each set of phospholipids from cornea and sclera. Significant
      differences exist between the corneal stroma and the sclera in 9 of the 12
      phospholipids, whereas differences exist between the whole cornea and the sclera
      in 7 of the 12 phospholipids.

PMID- 2001938
TI  - Quantitative enumeration of acanthamoeba for evaluation of cyst inactivation in
      contact lens care solutions.
AB  - A simple, quantitative plate assay has been developed for use in the enumeration
      of Acanthamoeba. The technique uses an agarose overlay and low-nutrient medium to
      support the growth of amoebae on a bacterial lawn. The authors found that in this
      assay, individual trophozoites or dormant cysts will cause plaques to form in an
      Enterobacter aerogenes lawn. With the assay, it is possible to quantitatively
      assess the effects of various disinfectant compounds on the viability of
      Acanthamoeba. The authors used this assay to enumerate Acanthamoeba cyst
      viability after chemical disinfection in contact lens care solutions. The
      inactivation data indicated major differences among the four test solutions
      evaluated.

PMID- 2001937
TI  - Calcitonin gene-related peptide immunoreactive nerve fibers in the rat
      conjunctiva.
AB  - Calcitonin gene-related peptide (CGRP) immunoreactive nerve fibers were studied
      in the rat conjunctiva by using indirect immunohistochemistry. Their origin was
      evaluated in a series of experiments where the animals were denervated by
      electrocoagulating the two first branches of the trigeminal nerve or by
      surgically extirpating the superior cervical ganglion. The CGRP-immunoreactive
      nerve fibers were seen mainly as thin varicose fibers in the epithelium and in
      the stroma. Many of the stromal fibers showed no apparent destination. However,
      CGRP-immunoreactive fibers were commonly found in association with stromal blood
      vessels, the smooth muscle of Muller, and the meibomian glands. Approximately 40%
      of the ganglion cells in the trigeminal ganglion were immunoreactive to CGRP. In
      the superior cervical ganglion, a few CGRP-immunoreactive fibers were seen
      although the ganglion cells were negative. After trigeminal denervation, all the
      epithelial and most of the stromal CGRP-immunoreactive nerve fibers disappeared.
      Sympathectomy had no effect on the presence of the CGRP-immunoreactive fibers.
      These observations indicate that most of the CGRP-immunoreactive nerve fibers in
      the rat conjunctiva are sensory nerves originating in the trigeminal ganglion. A
      few of the demonstrated fibers are, however, resistant to the sensory denervation
      and may be parasympathetic in their origin.

PMID- 2001939
TI  - Investigative Ophthalmology and Visual Science, annual meeting. Abstract issue.
      April 28-May 3, 1991. Sarasota, Florida.

PMID- 2001940
TI  - Making accurate final impressions for the fabrication of complete dentures. 2.
      Mandibular impressions.

PMID- 2001941
TI  - Meeting the nursing home challenge.

PMID- 2001942
TI  - Diagnostic exercise--recurrent oral ulcerations. 2. Differential diagnosis.

PMID- 2001943
TI  - Comparison of systemic plutonium deposition estimates from urinalysis and autopsy
      data in five whole-body donors.
AB  - The systemic deposition of (239 + 240)Pu was determined by postmortem
      radiochemical analysis of the tissues from five whole-body donors to the United
      States Transuranium Registry (USTR). All were males with intakes typically
      occurring many years prior to death. The postmortem radiochemical results were
      compared with estimates of systemic deposition made with 13 different biokinetic
      models using urinary excretion data obtained during life. In general, estimates
      made with older biokinetic models were severalfold greater than those obtained
      from radiochemical analysis of the tissues. For all five cases, agreement within
      a factor of two with the tissue analysis results was obtained with two of the
      biokinetic models evaluated: the Langham power function model as modified by
      Leggett and Eckerman and the two compartment exponential model proposed in ICRP
      Publication Nos. 19 and 30.

PMID- 2001944
TI  - Radon exposure, cigarette smoking, and other mining experience in the beaverlodge
      uranium miners cohort.
AB  - A nested case-control study within the Beaverlodge Uranium Miners Cohort was
      undertaken to assess any possible contribution of confounding by smoking and
      other mining experience to the risk estimate derived from the original cohort
      study. Next of kin have been interviewed for 46 lung cancer cases and 95 controls
      enrolled in the Beaverlodge Uranium Miners Cohort Study who died between 1950 and
      1980. Confounding by cigarette smoking and other mining experience appears
      unlikely to have contributed to the relative risk coefficient for exposure to Rn
      decay products derived in the parent study. Data for smoking and exposure to Rn
      decay products are consistent with a multiplicative model, although considerable
      caution must be applied to this interpretation.

PMID- 2001945
TI  - Comparative performance of short-term diffusion barrier charcoal canisters and
      long-term alpha-track monitors for indoor 222Rn measurements.
AB  - The accuracy and precision of indoor 222Rn measurements obtained with the use of
      diffusion barrier charcoal canisters (DBCC) under actual field conditions were
      determined by comparing the integrated average of 26 successive 7-d exposures of
      DBCC in each of 16 occupied residences over a 6-mo period with simultaneous
      measurements using four types of commercially available alpha-track monitors
      (ATM) and one type of scintillation chamber continuous 222Rn monitor. The results
      suggest that properly calibrated DBCCs provide very good estimates of the
      integrated 222Rn concentrations in residential structures over the standard 1-wk
      exposure period despite the occurrence of large diurnal variations in the actual
      222Rn concentrations. The results also suggest that a relatively small number of
      1-wk DBCC measurements at selected times throughout the calendar year would
      provide estimates of the annual average indoor 222Rn concentrations that compare
      favorably with single long-term ATM measurements.

PMID- 2001946
TI  - A performance evaluation study of three types of alpha-track detector radon
      monitors.
AB  - Three models of alpha-track detector (ATD) Rn monitors were exposed in
      Environmental Protection Agency (EPA) Rn chambers to obtain estimates of
      precision and bias for the National Residential Radon Survey (NRRS). Exposures in
      this study ranged from 37 to 740 Bq y m-3 (1 to 20 pCi y L-1), plus blanks. These
      exposures correspond to the range expected in most U.S. residences. All detectors
      were purchased through a Rn mitigation firm to assure that the vendors did not
      give special attention to the ATDs used in this study. Ten ATDs of each model
      were studied at 12 exposures. The mean and standard deviation of the reported
      values for each model were calculated and compared with the continuously
      monitored chamber concentrations to determine the bias and precision at each
      exposure. Results of this analysis were discussed with the vendors, who took
      corrective actions. Changes in track counting procedures and calibrations
      improved detector performance. Readings of one detector were adjusted based on a
      regression of the monitored values on the reported values.

PMID- 2001947
TI  - Radioiodine retention in ovine thyroids in northwestern Greece following the
      reactor accident at Chernobyl.
AB  - Iodine-131 concentrations were measured throughout the summer of 1986 in thyroids
      of lambs slaughtered at Ioannina (Northwestern Greece) following the accident at
      the Chernobyl nuclear reactor. During the survey, 40 thyroids were collected. The
      highest level of 131I detected was 2471 +/- 339 Bq per thyroid. The thyroids of
      20 lambs did not contain detectable 131I concentrations, while the contamination
      content of the others was greatly variable. The transport of 131I from pasture to
      thyroids of lambs has been described through a simple model for the retention of
      131I in the glands. The transfer coefficient fT, expressing the steady-state
      equilibrium, was estimated to be 564 +/- 270 kg-1 d. This result reflects the
      sensitivity of animal thyroids as biological radioiodine monitors.

PMID- 2001948
TI  - A validation test of a model for long-term retention of (129)I in surface soils.
AB  - A linear compartment model for global transport of iodine that we previously
      developed predicted that the mean residence time of iodine in the first 1 m of
      surface soil is about 4,000 y. An independent test of the model prediction is
      provided by measured depth profiles of (129)I in soil following atmospheric
      releases from the Savannah River Plant (SRP) in South Carolina and from the
      Karlsruhe fuel reprocessing plant in Germany. Previous analyses of these data
      using a linear compartment model for downward transport through soil indicated
      that the mean residence time in the first 0.3 m is about 40 y at both locations,
      which suggests that removal of (129)I from surface soil may be considerably more
      rapid than predicted by the global transport model. In this paper, a diffusion
      model is used to describe the measured soil profiles of (129)I at Savannah River.
      The diffusion coefficient obtained from the analysis corresponds to a mean
      residence time in the first 1 m of surface soil that agrees semi-quantitatively
      with the prediction of the global model when the concentration of naturally
      occurring stable iodine in soil and the flux of iodine from the atmosphere onto
      surface soil at Savannah River, as they differ from globally averaged values, are
      considered. This paper also discusses (1) the importance of the mean residence
      time of (129)I in surface soil for estimates of dose to individuals from near
      surface land disposal of low-level radioactive wastes and (2) unresolved issues
      regarding global cycling of iodine.

PMID- 2001949
TI  - High radiocesium levels in granite outcrop vegetation and reductions through
      time.
AB  - Levels of fallout radiocesium in vegetation were examined on three granite
      outcrops and a forested area in the Georgia piedmont during 1976-1980. Mean
      values averaged 4.3 times higher in three species collected on an outcrop than in
      the same species collected on clay soils in a nearby pine-hardwood forest. Levels
      in reindeer moss (Cladonia spp.) were significantly (p less than 0.01) lower in
      species that formed deep, entangled tufts with abundant, slender branches. Cesium
      levels decreased by as much as 90% from the mid-1960s but were virtually
      unchanged in the late 1970s. Dry-weight levels in mushrooms reached 18,470 Bq kg
      1 (499.2 pCi g-1). Radiation levels in outcrop vegetation were higher than values
      found anywhere in the piedmont and were comparable to levels reported in plants
      from the sterile sandy soils of the temperate region coastal plains. These data
      fit well with earlier reported values and correlate well with the availability of
      atmospheric fallout. Outcrops can be used as sensitive environmental barometers
      for some contaminants.

PMID- 2001951
TI  - Measurements of contact currents in radiofrequency fields.
AB  - Radiofrequency electromagnetic fields can affect human health not only by direct
      interactions but indirectly through induction of charges on isolated or poorly
      grounded conductive (metallic) objects located in these fields. A person who
      touches such an object may perceive a tingling or prickling sensation or heat, or
      experience pain or electric shock. For sufficiently large objects, these
      phenomena can occur at field strengths that are relatively low and below the
      health protection limits based on direct interactions. We describe a method and
      circuitry developed to evaluate steady-state contact currents that may flow
      through a person touching conductive objects and give a summary of experimental
      tests performed. The method is simple and viable for field tests aimed at
      preventing pain, shock, and burn hazards in radiofrequency electromagnetic fields
      except those related to spark discharges. The method is applicable up to about 30
      MHz.

PMID- 2001950
TI  - Distribution of radiocesium in the soil-plant systems of upland areas of Europe.
AB  - The distribution and behavior of Cs in the soil-plant systems at some upland
      sites in Northeastern Italy, Scotland, and Norway have been investigated. From
      the limited range of samples taken, there appears to be no dominant
      physicochemical control on the plant availability of Cs. The presence of
      micaceous minerals or illitic clays does not significantly inhibit Cs uptake,
      either because of recycling in the organic surface horizons or because of clay
      organic complex formation. Lower plants (bryophytes and lichens) show the highest
      Cs accumulation. Of the higher plants, ericaceous species take up Cs more than
      the others.

PMID- 2001952
TI  - Analytical relationships of nuclear field and microdosimetric quantities for
      target fragmentation in tissue systems.
AB  - A simple analytic formula for the nuclear fields formed by target fragmentation
      in tissue systems is derived using the continuous slowing down approximation
      (CSDA). The energy fluctuations in sensitive localized sites within the tissue
      system caused by these nuclear events are defined by microdosimetry. In that CSDA
      is used, the energy fluctuations exclude the role of secondary electrons. The
      relations also relate to the response of microdosimetric devices to nuclear
      fragmentation fields.

PMID- 2001954
TI  - Removal rates of Chernobyl fallout radioactivity on urban surfaces.

PMID- 2001953
TI  - Rn:Ra ratios in bone of beagles injected with 226Ra.

PMID- 2001955
TI  - Distribution of fallout radionuclides in soil, plants, and honey.

PMID- 2001956
TI  - Actinic region dosimetry.

PMID- 2001957
TI  - ALDOSE: a computer code to calculate absorbed-dose rate, dose-equivalent rate,
      and dose-weighted LET as functions of depth in water irradiated by an alpha
      particle disc source.

PMID- 2001958
TI  - Depth distribution of residual radioactivities in the concrete wall of an
      electron linac facility.

PMID- 2001959
TI  - Radiological assessment program for a broadscope by-product materials licensee.
AB  - A multilevel assessment program can be integrated into normal operational
      requirements and used to identify and correct operational errors. Assessments are
      made during routine surveys by field technicians, monthly by the Radiation Safety
      Officer, and biennially by an independent radiological expert. These systematic
      assessments can prevent the occurrence of significant program problems and result
      in a decreased number of Nuclear Regulatory Commission citations.

PMID- 2001960
TI  - Apparent dose equivalents resulting from severe heating of film dosimeters.
AB  - Unusual reported dose equivalents due to high-energy photons for two individuals
      prompted the investigation of the effects of severe heating conditions expected
      in closed vehicles during southwestern summer months on commercial film
      dosimeters. A historical review of dosimetry records revealed several additional
      reported high-energy photon exposures for individuals using only beta-emitting
      radioisotopes during hot summer months. Between 20-100% of experimentally heated
      badges had apparent dose equivalents exceeding the minimal detectable dose
      equivalent that were not flagged as being heat damaged or having unusual exposure
      patterns by the dosimetry companies. Reported dose equivalents for these badges
      were as high as 2.1 mSv.

PMID- 2001962
TI  - Radon leakage from liquid scintillation vials.

PMID- 2001961
TI  - Ethics and communication: a reply to Barker.

PMID- 2001963
TI  - The Roentgen rays.

PMID- 2001964
TI  - Labour Party: coming up roses.

PMID- 2001965
TI  - Support workers: handle with caution.

PMID- 2001966
TI  - Public health and the community.

PMID- 2001967
TI  - Women, health and the environment.

PMID- 2001968
TI  - Screening babies for neuroblastoma.

PMID- 2001969
TI  - Using 'alternative' medicine.

PMID- 2001970
TI  - Taking health education to the villages. Interview by Mandy Macdonald.

PMID- 2001971
TI  - Crown cars. Revised guidelines: new deals.

PMID- 2001972
TI  - Working under stress.

PMID- 2001973
TI  - Autoimmunization against the neutrophil-specific NA1 antigen is associated with
      HLA-DR2.
AB  - A significant association of autoimmune neutropenia (AIN) in infants due to NA1
      specific autoantibodies and HLA-DR2 is reported. Nineteen of 26 infants
      presenting with AIN and NA1 autoantibodies possessed the DR2 antigen, while only
      one out of six children with AIN, but non-NA1-specific autoantibodies, was DR2
      positive. Furthermore, one adult patient with primary biliary cirrhosis and
      periods of neutropenia due to NA1 autoantibodies also carried the DR2 antigen.
      All DR2-negative patients were positive for DRw6. These findings indicate that a
      close relationship exists between autoimmunization against the NA1 antigen and
      HLA-DR2 and possibly also DRw6.

PMID- 2001974
TI  - How many probes are needed for HLA-DPB1 typing with sequence-specific
      oligonucleotide probes? A theoretical approach using computer simulation.
AB  - HLA-DP genotyping with sequence-specific oligonucleotides is used to detect known
      sequence variations in the polymorphic segments of the DPB1 second exon. This
      approach is a valuable method replacing the tedious cellular definition of DP
      polymorphism. We have addressed, by computer simulation, the question: what is
      the minimum number of probes needed to provide an unambiguous assignment of HLA
      DP alleles by genotyping of heterozygous individuals? We were able to reduce the
      number of probes in a set defining the presently known 22 different alleles and
      most of the heterozygous combinations to 18 probes. Only two pairs of allelic
      combinations cannot be distinguished by this method, neither with our optimized
      set of probes nor with any larger set comprising probes of reasonable length.
      This is because two pairs of alleles may be the result of a reciprocal genetic
      exchange. These two pairs, however, could be distinguished by family analysis,
      direct sequencing, or DNA amplification using specific primers chosen from the
      polymorphic ends of the DPB1 second exon.

PMID- 2001975
TI  - A novel DRB1 allele in DR2-positive American blacks.
AB  - Class II D region antigens of the major histocompatibility complex are naturally
      occurring dimeric proteins found on the surface of lymphoid cells. In most
      haplotypes at least two of the polymorphic beta chains are associated with a
      nonpolymorphic alpha chain. The allelic variation of these proteins lies in the
      first domain of the expressed protein. At present, there are four known DRB
      genes. DRB1 encodes for the classical DR 1, 3, 4, 5, etc., specificities. DRB3
      and DRB4 encode the four supertypic specificities of DRw52 and the single
      phenotype of DRw53, respectively. Two DRB genes are expressed in human leukocyte
      antigen DR2-positive individuals. While DRB1 is the more polymorphic gene in most
      haplotypes, in DR2 haplotypes it appears that DRB5 encodes the polymorphic DR
      beta chain and the DRB1 encodes a nonpolymorphic beta chain. We attempted to
      further define the diversity of this region by direct dideoxynucleotide
      sequencing of polymerase-chain-reaction-amplified genomic DNA. We identified a
      novel DRB1 allele in DR2-positive individuals that was only observed in the
      American blacks sampled. This allele may code for a black specific class II
      antigen.

PMID- 2001976
TI  - DNA typing for class II HLA antigens with allele-specific or group-specific
      amplification. III. Typing for 24 alleles of HLA-DP.
AB  - The second exon of HLA-DPB includes five polymorphic segments with extensive
      sharing of sequences between alleles. In order to facilitate assignment of
      specificities in heterozygous individuals, we have used group-specific
      amplification of two nonoverlapping sets of DPB alleles (here called group A and
      group B) with especially designed primers. Group A and group B polymerase chain
      reaction products were hybridized with sequence-specific oligonucleotide probes
      generating easily recognizable patterns which defined 24 distinct HLA-DPB
      alleles. We also established a routine procedure for distinguishing HLA-DP
      homozygosity from failed amplification in one of the alleles. Our results showed
      that when only one allele was detected, failure of amplification had occurred in
      less than 4% of the cases. DNA typing with this method correlated well with
      primed-lymphocyte typing for HLA-DP in the Tenth Workshop, as determined by us in
      assays performed on the workshop B-cell lines. Two normal panels of unrelated
      subjects were tested to obtain population frequencies. We conclude that this
      method is simple, relatively quick, and accurate. It is the method of choice for
      studies to determine the role of HLA-DP alleles in T cell reactions, in various
      diseases, and in transplantation.

PMID- 2001977
TI  - HLA-DQA1 and HLA-DQB1 genes may jointly determine susceptibility to develop
      multiple sclerosis.
AB  - Serologic DR typing and genomic DRB1, DQA1, DQB1, DPA1, and DPB1 typing using
      sequence-specific oligonucleotides were performed in 69 multiple sclerosis (MS)
      patients and 181 healthy controls on in vitro amplified DNA. The frequencies of
      DR2 as well as the DR2-associated DQA1*0102 and DQB1*0602 alleles were increased
      whereas DR7 was decreased among MS patients. The distribution of DR4 subtypes as
      well as DP alleles were similar in patients and healthy controls. All but one of
      23 DR4-positive MS patients carried the DQB1*0302 allele, whereas five of five
      DR7-positive MS patients carried the DQB1*0303 allele. Of the MS patients, 99%
      compared to 79% of the controls carried DQA1 alleles encoding glutamine at
      residue 34, while 97% of the MS patients compared to 72% of the controls carried
      DQB1 alleles encoding DQ beta chains sharing long polymorphic stretches. A
      combination of such DQA1 and DQB1 alleles was carried by 96% of the MS patients
      and 60% of the controls, suggesting an association between MS and a combination
      of particular DQA1 alleles and DQB1 alleles. The corresponding DQ alpha beta
      heterodimers may have in common an ability to bind a particular peptide.

PMID- 2001978
TI  - B27-bearing HLA haplotypes in rheumatoid arthritis: characterization in Finnish
      patients.
AB  - The frequency of human leukocyte antigen (HLA)-B27 has been found to be increased
      in rheumatoid arthritis (RA) in Finland and marginally also in some other
      populations. In the present study HLA-B27-bearing haplotypes in RA patients were
      found to carry DR1 and DR4 genes more often than do B27 haplotypes in control
      population. B27;DR4,DW14;DQw7 was a typical B27-DR4 haplotype whereas DR4 in the
      majority of other haplotypes occurs with Dw4 and DQw8 genes. The result indicates
      that the B27 association with RA is not independent of DR1 and DR4, but whether
      the B27;DR4;DQw7 haplotype subjects a person to a higher disease risk than do
      other DR4 haplotypes, or is associated with a more severe course of the disease,
      remains to be investigated.

PMID- 2001979
TI  - Gamma-lactam analogues of beta-lactam antibiotics.

PMID- 2001980
TI  - 6-O-demethyl-5-deoxyfusarubin and its anhydro derivative produced by a mutant of
      the fungus Nectria haematococca blocked in fusarubin biosynthesis.
AB  - 6-O-Demethyl-5-deoxyfursarubin and 6-O-demethyl-5-deoxyanhydrofusarubin have been
      isolated from the mutant redD169.yelY9 of the fungus Nectria haematococca blocked
      in fusarubin biosynthesis. These products were identified on the basis of physico
      chemical data by comparison with known substances.

PMID- 2001981
TI  - Structure of lactacystin, a new microbial metabolite which induces
      differentiation of neuroblastoma cells.

PMID- 2001982
TI  - Mannan-mediated anticandidal activity of BMY-28864, a new water-soluble
      pradimicin derivative.

PMID- 2001983
TI  - Sapurimycin, new antitumor antibiotic produced by Streptomyces. Producing
      organism, fermentation, isolation and biological properties.
AB  - In screening actinomycetes for antitumor compounds, Streptomyces sp. DO-116 was
      found to produce a new antitumor antibiotic sapurimycin. It is structurally
      related to, but distinct from, kapurimycins. The antibiotic was produced in a
      fermentation medium supplemented with high porous polymer resin which adsorbs
      antibiotic in the culture and results in an increase of titer. Active material
      was separated from the polymer resin by a solvent extraction procedure and
      isolated by repeated solvent extraction, adsorption chromatography and HPLC.
      Sapurimycin was active against bacteria, particularly Gram-positive organisms. It
      exhibited antitumor activity against leukemia P388 and sarcoma 180 in mice.
      Sapurimycin caused single strand breaks in supercoiled plasmid DNA in vitro.
      These results are discussed in comparison with data for kapurimycins.

PMID- 2001984
TI  - Sapurimycin, new antitumor antibiotic produced by Streptomyces. Structure
      determination.
AB  - The structure of a new anthra-gamma-pyrone antitumor antibiotic sapurimycin was
      determined by the spectral studies of its methyl ester. Sapurimycin has the same
      anthra-gamma-pyrone skeleton as pluramycin, but is distinctly different because
      of the absence of sugars on the D ring and possessing a carboxylmethyl group on C
      5.

PMID- 2001985
TI  - L-687,781, a new member of the papulacandin family of beta-1,3-D-glucan synthesis
      inhibitors. I. Fermentation, isolation, and biological activity.
AB  - A new beta-1,3-D-glucan synthesis inhibitor, L-687,781 is produced by the
      cultivation of Dictyochaeta simplex ATCC 20960. L-687,781 exhibits potent in
      vitro antifungal activity as well as anti-Pneumocystis activity in a rat model.

PMID- 2001986
TI  - Studies on macrocyclic lactone antibiotics. XIII. Anti-tubulin activity and
      cytotoxicity of rhizoxin derivatives: synthesis of a photoaffinity derivative.
AB  - Chemical modification of the side chain in rhizoxin, a potent antimitotic agent,
      was attempted in order to study structure-activity relationships and also to
      devise a probe for photoaffinity labeling of tubulin. An OsO4/NaIO4 oxidation
      gave a nor-rhizoxin 20-al (5) which was converted to 20-ol (6) by a NaBH3CN
      reduction. Starting from these two compounds as key intermediates, a series of
      Wittig reaction products 7-2, and of 20-O-acylates 13-21 were prepared and their
      anti-tubulin activity and cytotoxicity were determined. An aryl azide derivative
      23 was synthesized as a photoaffinity analogue.

PMID- 2001987
TI  - A rapid colorimetric microassay to detect agonists/antagonists of protein kinase
      C based on adherence of EL-4.IL-2 cells.
AB  - A rapid, colorimetric, microassay for detection of agents which are known
      agonists/antagonists of protein kinase C (PKC) was developed, utilizing their
      effects on adherence of EL-4.IL-2 cells. Cells that were incubated with agents
      which are known inducers of PKC activation, phorbol 12-myristate 13-acetate
      (PMA), phorbol 12,13-dibutyrate (PDBu), mezerein and indolactam V, readily
      adhered to wells of 96 well microtiter plates within 1-2 hours, whereas cells
      incubated with the negative PKC activator, 4 alpha-phorbol 12-myristate 13
      acetate (4 alpha-PMA), which is structurally related to PMA (4 beta-PMA), did not
      adhere. The adherent cells withstood repeated vigorous washings with tissue
      culture medium. Adherence of EL-4.IL-2 cells in the presence of PMA could be
      blocked by the addition of two known inhibitors of PKC, 1-(5-isoquinoline
      sulfonyl)-2-methylpiperazine dihydrochloride and staurosporine. Detection of the
      presence of adherent cells was accomplished by the addition of a tetrazolium salt
      to culture wells and determination of the remaining viable cells by scanning
      using a multiwell spectrophotometer (ELISA reader). The EL-4.IL-2 adherence assay
      meets several important criteria for use as a primary screen in the detection of
      potential PKC agonists/antagonists, i.e. its selectivity, simplicity, rapid
      performance through automation and reproducibility.

PMID- 2001988
TI  - Tuberculosis and HIV.

PMID- 2001989
TI  - Three trans-acting regulatory functions control hydrogenase synthesis in
      Alcaligenes eutrophus.
AB  - Random Tn5 mutagenesis of the regulatory region of megaplasmid pHG1 of
      Alcaligenes eutrophus led to the identification of three distinct loci designated
      hoxA, hoxD, and hoxE. Sequencing of the hoxA locus revealed an open reading frame
      which could code for a polypeptide of 482 amino acids with a molecular mass of
      53.5 kDa. A protein of comparable apparent molecular mass was detected in
      heterologous expression studies with a plasmid-borne copy of the hoxA gene. Amino
      acid alignments revealed striking homologies between HoxA and the transcriptional
      activators NifA and NtrC of Klebsiella pneumoniae and HydG of Escherichia coli.
      HoxA- mutants of A. eutrophus lacked both NAD-reducing soluble hydrogenase and
      membrane-bound hydrogenase. In HoxA- mutants, the synthesis of beta-galactosidase
      from a hoxS'-'lacZ operon fusion was drastically reduced, indicating that HoxA is
      essential for the transcription of hydrogenase genes. Mutants defective in hoxD
      and hoxE also lacked the catalytic activities of the two hydrogenases; however,
      in contrast to HoxA- mutants, they contained immunologically detectable NAD
      reducing soluble hydrogenase and membrane-bound hydrogenase proteins, although at
      a reduced level. The low hydrogenase content in the HoxD- and HoxE- mutants
      correlated with a decrease in beta-galactosidase synthesized under the direction
      of a hoxS'-'lacZ operon fusion. Thus, hoxD and hoxE apparently intervene both in
      the regulation of hydrogenase synthesis and in subsequent steps leading to the
      formation of catalytically active enzymes.

PMID- 2001990
TI  - Structure, serological specificity, and synthesis of artificial glycoconjugates
      representing the genus-specific lipopolysaccharide epitope of Chlamydia spp.
AB  - The human bacterial pathogens Chlamydia spp. possess a genus-specific
      lipopolysaccharide as a major surface antigen, the structure of which has been
      determined by analytical chemistry as Kdop alpha 2-8-Kdop alpha 2-4-Kdop alpha 2
      6GlcNp beta 1-6-GlcNol (Kdo, 3-deoxy-D-manno-2-octulosonic acid). Immunochemical
      studies on this pentasaccharide and the chemically synthesized partial structures
      Kdop alpha 2-8-Kdop alpha 2-4-Kdop alpha 2-6GlcNp beta, Kdop alpha 2-8-Kdop alpha
      2-4-Kdop alpha, Kdop alpha 2-4-Kdop alpha, Kdop alpha 2-8-Kdop alpha, and Kdop
      alpha using artificial glycoconjugate antigens and monoclonal antibodies showed
      that fatty acids and phosphoryl groups (as present in native lipopolysaccharide)
      are dispensable for constitution of the genus-specific epitope and that the
      minimal structure to exhibit chlamydia specificity is the Kdo trisaccharide
      moiety.

PMID- 2001991
TI  - A diffusible compound can enhance conjugal transfer of the Ti plasmid in
      Agrobacterium tumefaciens.
AB  - Several octopine strains of Agrobacterium tumefaciens were tested for Ti plasmid
      (pTi) transfer after induction by 400 micrograms of octopine per ml for 24 h. The
      strains could be divided into two groups, transfer efficient (Trae) and transfer
      inefficient (Traie); the respective rates of transfer were 0.77 x 10(-2) to 1.14
      x 10(-2) and 0.33 x 10(-6) to 9.8 x 10(-6) plasmid transconjugant per donor cell.
      Transfer efficiencies of Traie strains were greatly increased when the time of
      induction was 72 h. A diffusible conjugation factor (CF) that can enhance
      conjugal transfer of pTi in A. tumefaciens was discovered when both Trae and
      Traie donor strains were induced in the same plate. The evidence indicates that
      CF is a key factor affecting transfer efficiency of pTi but is not sufficient by
      itself to induce transfer. Trac mutants can produce CF constitutively, and Trae
      strains can produce it after induction by low octopine concentrations. The
      transfer efficiency of Traie strains was greatly increased by adding CF to the
      induction medium. The thermosensitive strain B6S, which normally cannot conjugate
      at temperatures above 30 degrees C, could transfer pTi efficiently at 32 and 34
      degrees C in the presence of CF. Production of CF is dependent on the presence of
      pTi but appears to be common for different opine strains; it was first detected
      in octopine strains, but nopaline strains also produced the same or a similar
      compound. CF is very biologically active, affecting donor but not recipient
      bacterial cells, but CF does not promote aggregation. Data suggest that CF might
      be an activator or derepressor in the conjugation system of A. tumefaciens. CF is
      a dialyzable small molecule and is resistant to DNase, RNase, protease, and
      heating to 100 degrees C for 10 min, but autoclaving (121 degrees C for 15 min)
      and alkaline treatment removed all activity.

PMID- 2001992
TI  - Stoichiometry of maltodextrin-binding sites in LamB, an outer membrane protein
      from Escherichia coli.
AB  - We have directly measured the stoichiometry of maltodextrin-binding sites in
      LamB. Scatchard plots and computer fitting of flow dialysis (rate-of-dialysis)
      experiments clearly establish three independent binding sites per LamB trimer,
      with a dissociation constant of approximately 60 microM for maltoheptaose. The
      current model for LamB's function as a specific pore is discussed with respect to
      the symmetry in LamB's kinetic properties and the implications of our results.

PMID- 2001993
TI  - Relative activities and stabilities of mutant Escherichia coli tryptophan
      synthase alpha subunits.
AB  - In vitro mutagenesis of the Escherichia coli trpA gene has yielded 66 mutant
      tryptophan synthase alpha subunits containing single amino acid substitutions at
      49 different residue sites and 29 double and triple amino acid substitutions at
      16 additional sites, all within the first 121 residues of the protein. The 66
      singly altered mutant alpha subunits encoded from overexpression vectors have
      been examined for their ability to support growth in trpA mutant host strains and
      for their enzymatic and stability properties in crude extracts. With the
      exception of mutant alpha subunits altered at catalytic residue sites Glu-49 and
      Asp-60, all support growth; this includes those (48 of 66) that have no enzymatic
      defects and those (18 of 66) that do. The majority of the enzymatically defective
      mutant alpha subunits have decreased capacities for substrate (indole-3-glycerol
      phosphate) utilization, typical of the early trpA missense mutants isolated by in
      vivo selection methods. These defects vary in severity from complete loss of
      activity for mutant alpha subunits altered at residue positions 49 and 60 to
      those, altered elsewhere, that are partially (up to 40 to 50%) defective. The
      complete inactivation of the proteins altered at the two catalytic residue sites
      suggest that, as found via in vitro site-specific mutagenesis of the Salmonella
      typhimurium tryptophan synthetase alpha subunit, both residues probably also
      participate in a push-pull general acid-base catalysis of indole-3-glycerol
      phosphate breakdown for the E. coli enzyme as well. Other classes of mutant alpha
      subunits include some novel types that are defective in their functional
      interaction with the other tryptophan synthetase component, the beta 2 subunit.
      Also among the mutant alpha subunits, 19 were found altered at one or another of
      the 34 conserved residue sites in this portion of the alpha polypeptide sequence;
      surprisingly, 10 of these have wild-type enzymatic activity, and 16 of these can
      satisfy growth requirements of a trpA mutant host. Heat stability and potential
      folding-rate alterations are found in both enzymatically active and defective
      mutant alpha subunits. Tyr-4. Pro-28, Ser-33, Gly-44, Asp-46, Arg-89, Pro-96, and
      Cys-118 may be important for these properties, especially for folding. Two
      regions, one near Thr-24 and another near Met-101, have been also tentatively
      identified as important for increasing stability.

PMID- 2001994
TI  - Nucleotide sequence of the Escherichia coli micA gene required for A/G-specific
      mismatch repair: identity of micA and mutY.
AB  - The Escherichia coli methylation-independent repair pathway specific for A/G
      mismatches has been shown to require the gene product of micA. Extracts prepared
      from micA mutants do not form an A/G mismatch-specific DNA-protein complex and do
      not contain an A/G mismatch-specific nicking activity. Moreover, a partially
      purified protein fraction containing both A/G mismatch-specific nicking and
      binding activities restores repair activity in micA mutant extracts. The DNA
      sequence of a 2.3-kb fragment containing the micA gene has been determined. There
      are two open reading frames (ORF) in this DNA fragment: one ORF encodes a 25.7
      kDa protein whose function is still unknown, the other ORF codes for a protein
      with an Mr of 39,147, but this ORF can be transcribed and the mRNA can be
      translated to yield a protein with an apparent Mr of 36 kDa on a sodium dodecyl
      sulfate-polyacrylamide gel. Deletion analysis showed that this 39.1-kDa ORF is
      the micA gene as judged by the capacity of the encoded protein to restore the A/G
      mismatch-specific nicking activity of micA mutant extracts. Furthermore, our
      results suggest that micA is the same gene as the closely mapped mutY, which
      encodes the A/G mismatch-specific glycosylase.

PMID- 2001996
TI  - 3-(2-hydroxyphenyl)catechol as substrate for proximal meta ring cleavage in
      dibenzofuran degradation by Brevibacterium sp. strain DPO 1361.
AB  - Brevibacterium sp. strain DPO 1361 oxygenates dibenzofuran in the unusual angular
      position. The 3-(2-hydroxyphenyl)catechol thus generated is subject to meta ring
      cleavage in the proximal position, yielding 2-hydroxy-6-(2-hydroxyphenyl)-6-oxo
      2,4-hexadienoic acid, which is hydrolyzed to 2-oxo-4-pentenoate and salicylate by
      2-hydroxy-6-oxo-6-phenyl-2,4-hexadienoic acid hydrolase. The proximal mode of
      ring cleavage is definitely established by isolation and unequivocal structural
      characterization of a cyclization product of 2-hydroxy-6-(2-hydroxyphenyl)-6-oxo
      2,4-hexadienoic acid, i.e., 3-(chroman-4-on-2-yl)pyruvate.

PMID- 2001995
TI  - Shuttle cloning and nucleotide sequences of Helicobacter pylori genes responsible
      for urease activity.
AB  - Production of a potent urease has been described as a trait common to all
      Helicobacter pylori so far isolated from humans with gastritis as well as peptic
      ulceration. The detection of urease activity from genes cloned from H. pylori was
      made possible by use of a shuttle cosmid vector, allowing replication and
      movement of cloned DNA sequences in either Escherichia coli or Campylobacter
      jejuni. With this approach, we cloned a 44-kb portion of H. pylori chromosomal
      DNA which did not lead to urease activity when introduced into E. coli but
      permitted, although temporarily, biosynthesis of the urease when transferred by
      conjugation to C. jejuni. The recombinant cosmid (pILL585) expressing the urease
      phenotype was mapped and used to subclone an 8.1-kb fragment (pILL590) able to
      confer the same property to C. jejuni recipient strains. By a series of deletions
      and subclonings, the urease genes were localized to a 4.2-kb region of DNA and
      were sequenced by the dideoxy method. Four open reading frames were found,
      encoding polypeptides with predicted molecular weights of 26,500 (ureA), 61,600
      (ureB), 49,200 (ureC), and 15,000 (ureD). The predicted UreA and UreB
      polypeptides correspond to the two structural subunits of the urease enzyme; they
      exhibit a high degree of homology with the three structural subunits of Proteus
      mirabilis (56% exact matches) as well as with the unique structural subunit of
      jack bean urease (55.5% exact matches). Although the UreD-predicted polypeptide
      has domains relevant to transmembrane proteins, no precise role could be
      attributed to this polypeptide or to the UreC polypeptide, which both mapped to a
      DNA sequence shown to be required to confer urease activity to a C. jejuni
      recipient strain.

PMID- 2001997
TI  - Purification and properties of an organophosphorus acid anhydrase from a
      halophilic bacterial isolate.
AB  - A moderately halophilic bacterial isolate has been found to possess high levels
      of enzymatic activity against several highly toxic organophosphorus compounds.
      The predominant enzyme, designated organophosphorus acid anhydrase 2, has been
      purified 1,000-fold to homogeneity and characterized. The enzyme is a single
      polypeptide with a molecular weight of 60,000. With diisopropylfluorophosphate as
      a substrate, the enzyme has optimum activity at pH 8.5 and 50 degrees C, and it
      is stimulated by manganese and cobalt.

PMID- 2001998
TI  - Hierarchies of base pair preferences in the P22 ant promoter.
AB  - Oligonucleotide-directed mutagenesis was used to complete a collection of
      mutations in the -35 and -10 hexamers of the ant promoter of Salmonella phage
      P22. The effects of all 36 single-base-pair substitutions on promoter strength in
      vivo were measured in strains carrying the mutant promoters fused to an ant-lacZ
      gene on a single-copy prophage. The results of these assays show that certain
      consensus base pairs are more important than others; in general, the least
      critical positions are among the most poorly conserved. Some mutations within the
      hexamers have smaller effects on promoter strength than certain mutations outside
      the hexamers in this and other promoters. Several different patterns of base pair
      preferences are observed. These hierarchies of base pair preferences correlate
      well (but not perfectly) with the hierarchies defined by the frequency
      distribution of base pairs at each position among wild-type promoters. The
      hierarchies observed in the ant promoter also agree well with most of the
      available information on base pair preferences in other promoters.

PMID- 2001999
TI  - Partial characterization of a lysU mutant of Escherichia coli K-12.
AB  - The Escherichia coli K-12 strain GNB10181 shows no inducible lysyl-tRNA
      synthetase (LysRS) activity. Two-dimensional gel electrophoretic analysis of the
      polypeptides synthesized by this strain indicates that the normal lysU gene
      product, LysU, is absent. When both GNB10181 and its parent, MC4100, were grown
      at elevated temperatures (42 to 45 degrees C) no significant difference between
      their growth rates was observed. The lysU mutation was transferred to other E.
      coli K-12 backgrounds by using P1 transduction. The lysU transductants behaved
      comparably to their lysU+ parents at different growth temperatures. Therefore,
      the LysU proteins does not appear to be essential for growth at high
      temperatures, at least under the conditions examined here. In addition, lysU
      transductants were found to be defective for inducible lysine decarboxylase,
      (LDC), inducible arginine decarboxylase (ADI), and melibiose utilization (Mel),
      which are all missing in GNB10181. Complementation of the above missing functions
      was achieved by using the Clarke-Carbon plasmids pLC4-5 (LysU LDC) and pLC17-38
      (LysU Mel ADI). From these experiments, it appears that GNB10181 has suffered a
      chromosomal deletion between 93.4 and 93.7 min, which includes the lysU gene. By
      using plasmid pLC17-38, the position of ADI on two-dimensional gels was
      identified. Finally, lysS delta lysU double mutants were constructed which can
      potentially be used as positive selection agents for the isolation of LysRS genes
      from other sources.

PMID- 2002000
TI  - Rotation and switching of the flagellar motor assembly in Halobacterium halobium.
AB  - Halobacterium halobium swims with a polarly inserted motor-driven flagellar
      bundle. The swimming direction of the cell can be reserved by switching the
      rotational sense of the bundle. The switch is under the control of photoreceptor
      and chemoreceptor proteins that act through a branched signal chain. The swimming
      behavior of the cells and the switching process of the flagellar bundle were
      investigated with a computer-assisted motion analysis system. The cells were
      shown to swim faster by clockwise than by counterclockwise rotation of the
      flagellar bundle. From the small magnitude of speed fluctuations, it is concluded
      that the majority, if not all, of the individual flagellar motors of a cell
      rotate in the same direction at any given time. After stimulation with light
      (blue light pulse or orange light step-down), the cells continued swimming with
      almost constant speed but then slowed before they reversed direction. The cells
      passed through a pausing state during the change of the rotational sense of the
      flagellar bundle and then exhibited a transient acceleration. Both the average
      length of the pausing period and the transient acceleration were independent of
      the stimulus size and thus represent intrinsic properties of the flagellar motor
      assembly. The average length of the pausing period of individual cells, however,
      was not constant. The time course of the probability for spontaneous motor
      switching was calculated from frequency distribution and shown to be independent
      of the rotational sense. The time course further characterizes spontaneous
      switching as a stochastic rather than an oscillator-triggered event.

PMID- 2002001
TI  - Role of RpoH, a heat shock regulator protein, in Escherichia coli carbon
      starvation protein synthesis and survival.
AB  - Escherichia coli starvation proteins include several heat shock proteins whose
      induction by heat is controlled by the minor sigma factor, sigma 32. The level of
      sigma 32 increased in wild-type E. coli upon starvation, and three sigma 32
      controlled heat shock proteins (DnaK, GroEL, and HtpG) were not induced during
      starvation in an isogenic delta rpoH strain, which is unable to synthesize sigma
      32. Thus, sigma 32 plays a role in the induction of these proteins during both
      heat shock and starvation. The delta rpoH strain was more sensitive to starvation
      but could develop starvation-mediated cross protection against heat and
      oxidation.

PMID- 2002002
TI  - Effect of OmpA signal peptide mutations on OmpA secretion, synthesis, and
      assembly.
AB  - In previous investigations, we have examined the effect of OmpA signal peptide
      mutations on the secretion of the two heterologous proteins TEM beta-lactamase
      and nuclease A. During these studies, we observed that a given signal peptide
      mutation could affect differentially the processing of precursor OmpA-nuclease or
      precursor OmpA-lactamase. This observation led us to further investigate the
      influence of the mature region of a precursor protein on protein export.
      Preexisting OmpA signal peptide mutations of known secretion phenotype when
      directing heterologous protein export (nuclease A or beta-lactamase) were fused
      to the homologous mature OmpA protein. Four signal peptide mutations that have
      previously been shown to prevent export of nuclease A and beta-lactamase were
      found to support OmpA protein export, albeit at reduced rates. This remarkable
      retention of export activity by severely defective precursor OmpA signal peptide
      mutants may be due to the ability of mature OmpA to interact with the cytoplasmic
      membrane. In addition, these same signal peptide mutations can affect the level
      of OmpA synthesis as well as its proper assembly in the outer membrane of
      Escherichia coli. Two signal peptide mutations dramatically stimulate the rate of
      precursor OmpA synthesis three- to fivefold above the level observed when a wild
      type signal peptide is directing export. The complete removal of the OmpA signal
      peptide does not result in increased OmpA synthesis. This finding suggests that
      the signal peptide mutations function positively to stimulate OmpA synthesis,
      rather than bypass a down-regulatory mechanism effected by a wild-type signal
      peptide. Overproduction of wild-type precursor OmpA or precursors containing
      signal peptide mutations which lead to relatively minor kinetic processing
      defects results in accumulation of an improperly assembled OmpA species (imp
      OmpA). In contrast, signal peptide mutations which cause relatively severe
      processing defects accumulate no or only small quantities of imp-OmpA. All
      mutations result in equivalent levels of properly assembled OmpA. Thus, a strong
      correlation between imp-OmpA accumulation and cell toxicity was observed. A
      mutation in the mature region of OmpA which prevents the proper outer membrane
      assembly of OmpA was suppressed when export was directed by a severely defective
      signal peptide. These findings suggest that signal peptide mutations indirectly
      influence OmpA assembly in the outer membrane by altering both the level and rate
      of OmpA secretion across the cytoplasmic membrane.

PMID- 2002003
TI  - A novel Saccharomyces cerevisiae secretory mutant possesses a thermolabile
      phosphomannose isomerase.
AB  - A temperature-sensitive mutant of Saccharomyces cerevisiae was identified which
      at the restrictive temperature of 37 degrees C is unable to secrete a number of
      cell wall-associated proteins and thus resembles previously reported sec mutants.
      In contrast to other sec mutants, however, both the temperature-sensitive growth
      and the secretion defects can be repaired by the addition of D-mannose to growth
      media. We show that the mutant possesses a single, apparently recessive mutation
      which leads to the production of a thermolabile phosphomannose isomerase.

PMID- 2002004
TI  - Cloning of Azorhizobium caulinodans nicotinate catabolism genes and
      characterization of their importance in N2 fixation.
AB  - Twenty Azorhizobium caulinodans vector insertion (Vi) mutants unable to
      catabolize nicotinate (Nic- phenotype) were identified and directly cloned as pVi
      plasmids. These pVi plasmids were used as DNA hybridization probes to isolate
      homologous wild-type sequences. From subsequent physical mapping experiments, the
      nic::Vi mutants defined four distinct loci. Two, possibly three, of these loci
      are physically linked. A. caulinodans nic loci II and III encode the structural
      genes for nicotinate catabolism; nic loci I and IV encode nicotinate-driven
      respiratory chain components. Recombinant lambda bacteriophages corresponding to
      three of these loci were subcloned in pRK293; resulting plasmids were used for
      complementation tests with resolved nic::IS50 derivatives of the nic::Vi mutants.
      When wild-type A. caulinodans was cultured in defined liquid medium under 3% O2,
      nicotinate catabolism stimulated N2 fixation 10-fold. In these exponentially
      growing cultures, the entire (300 microM) nicotinate supplement was exhausted
      within 10 h. While nic::Vi mutants retained the ability to fix some N2, they did
      so at rates only 10% of that of the wild type: nitrogenase activity by nic::Vi
      mutants was not stimulated by 300 microM added nicotinate. Higher-level (5 mM)
      nicotinate supplementation inhibited N2 fixation. Because 5 mM nicotinate
      repressed nitrogenase induction in all nic::Vi mutants as well, this repression
      was independent of nicotinate catabolism. During catabolism, nicotinate is first
      oxidized to 6-OH-nicotinate by a membrane-bound nicotinate hydroxylase which
      drives a respiratory chain to O2. In A. caulinodans wild-type cultures, added 300
      microM 6-OH-nicotinate stimulated N2 fixation twofold better than did added 300
      microM nicotinate. Likewise, nic::Vi mutant 61302, defective in nicotinate
      hydroxylase, fixed N2 at wild-type levels when supplemented with 300 microM 6-OH
      nicotinate. Therefore, nicotinate catabolism stimulates N2 fixation not by
      nicotinate hydroxylase-driven respiration but rather by some subsequent aspect(s)
      of nicotinate catabolism.

PMID- 2002005
TI  - Phospholipid synthesis and lipid composition of subcellular membranes in the
      unicellular eukaryote Saccharomyces cerevisiae.
AB  - Subcellular membranes of Saccharomyces cerevisiae, including mitochondria,
      microsomes, plasma membranes, secretory vesicles, vacuoles, nuclear membranes,
      peroxisomes, and lipid particles, were isolated by improved procedures and
      analyzed for their lipid composition and their capacity to synthesize
      phospholipids and to catalyze sterol delta 24-methylation. The microsomal
      fraction is heterogeneous in terms of density and classical microsomal marker
      proteins and also with respect to the distribution of phospholipid-synthesizing
      enzymes. The specific activity of phosphatidylserine synthase was highest in a
      microsomal subfraction which was distinct from heavier microsomes harboring
      phosphatidylinositol synthase and the phospholipid N-methyltransferases. The
      exclusive location of phosphatidylserine decarboxylase in mitochondria was
      confirmed. CDO-diacylglycerol synthase activity was found both in mitochondria
      and in microsomal membranes. Highest specific activities of glycerol-3-phosphate
      acyltransferase and sterol delta 24-methyltransferase were observed in the lipid
      particle fraction. Nuclear and plasma membranes, vacuoles, and peroxisomes
      contain only marginal activities of the lipid-synthesizing enzymes analyzed. The
      plasma membrane and secretory vesicles are enriched in ergosterol and in
      phosphatidylserine. Lipid particles are characterized by their high content of
      ergosteryl esters. The rigidity of the plasma membrane and of secretory vesicles,
      determined by measuring fluorescence anisotropy by using trimethylammonium
      diphenylhexatriene as a probe, can be attributed to the high content of
      ergosterol.

PMID- 2002006
TI  - Extragenic suppressors of yeast glucose derepression mutants leading to
      constitutive synthesis of several glucose-repressible enzymes.
AB  - Saccharomyces cerevisiae regulatory genes CAT1 and CAT3 constitute a positive
      control circuit necessary for derepression of gluconeogenic and disaccharide
      utilizing enzymes. Mutations within these genes are epistatic to hxk2 and hex2,
      which cause defects in glucose repression. cat1 and cat3 mutants are unable to
      grow in the presence of nonfermentable carbon sources or maltose. Stable gene
      disruptions were constructed inside these genes, and the resulting growth
      deficiencies were used for selecting epistatic mutations. The revertants obtained
      were tested for glucose repression, and those showing altered regulatory
      properties were further investigated. Most revertants belonged to a single
      complementation group called cat4. This recessive mutation caused a defect in
      glucose repression of invertase, maltase, and iso-1-cytochrome c. Additionally,
      hexokinase activity was increased. Gluconeogenic enzymes are still normally
      repressible in cat4 mutants. The occurrence of recombination of cat1::HIS3 and
      cat3::LEU2 with some cat4 alleles allowed significant growth in the presence of
      ethanol, which could be attributed to a partial derepression of gluconeogenic
      enzymes. The cat4 complementation group was tested for allelism with hxk2, hex2,
      cat80, cid1, cyc8, and tup1 mutations, which were previously described as
      affecting glucose repression. Allelism tests and tetrad analysis clearly proved
      that the cat4 complementation group is a new class of mutant alleles affecting
      carbon source-dependent gene expression.

PMID- 2002007
TI  - Isolation and structure of the lipid envelopes from the nitrogen-fixing vesicles
      of Frankia sp. strain CpI1.
AB  - Frankia vesicles are differentiated during nitrogen starvation; they contain
      nitrogenase whether produced by free-living frankiae or by frankiae in
      actinorhizal root nodules. Vesicles are surrounded by envelopes of several
      monolayers of uncharacterized lipid. It has been suggested that the envelope
      limits diffusion of O2 into the vesicle cytoplasm, thereby preventing
      inactivation of nitrogenase. Whole vesicles were prepared on sucrose gradients
      and sonicated, and vesicle envelopes were isolated on top of a cushion of 40%
      sucrose. Transmission electron microscopy of potassium permanganate-fixed
      envelopes confirmed the purity of these preparations. Only the outer and inner
      envelope layers were visible in permanganate-fixed intact vesicles; the laminae
      were not visible in aldehyde-osmium-fixed, lead citrate-uranyl acetate-stained
      whole vesicles. However, the laminated nature of the envelope was clearly evident
      in sonicated vesicles and in envelope fragments fixed with KMnO4. The
      observations indicate that partial disruption of the vesicle envelope enables its
      visualization with permanganate fixation, and these observations open the way for
      further studies on the relationship of the vesicle surface to environmental
      conditions.

PMID- 2002008
TI  - Increased spontaneous mutation and alkylation sensitivity of Escherichia coli
      strains lacking the ogt O6-methylguanine DNA repair methyltransferase.
AB  - Escherichia coli expresses two DNA repair methyltransferases (MTases) that repair
      the mutagenic O6-methylguanine (O6MeG) and O4-methylthymine (O4MeT) DNA lesions;
      one is the product of the inducible ada gene, and here we confirm that the other
      is the product of the constitutive ogt gene. We have generated various ogt
      disruption mutants. Double mutants (ada ogt) do not express any O6MeG/O4MeT DNA
      MTases, indicating that Ada and Ogt are probably the only two O6MeG/O4MeT DNA
      MTases in E. coli. ogt mutants were more sensitive to alkylation-induced
      mutation, and mutants arose linearly with dose, unlike ogt+ cells, which had a
      threshold dose below which no mutants accumulated; this ogt(+)-dependent
      threshold was seen in both ada+ and ada strains. ogt mutants were also more
      sensitive to alkylation-induced killing (in an ada background), and
      overexpression of the Ogt MTase from a plasmid provided ada, but not ada+, cells
      with increased resistance to killing by alkylating agents. The induction of the
      adaptive response was normal in ogt mutants. We infer from these results that the
      Ogt MTase prevents mutagenesis by low levels of alkylating agents and that, in
      ada cells, the Ogt MTase also protects cells from killing by alkylating agents.
      We also found that ada ogt E. coli had a higher rate of spontaneous mutation than
      wild-type, ada, and ogt cells and that this increased mutation occurred in
      nondividing cells. We infer that there is an endogenous source of O6MeG or O4MeT
      DNA damage in E. coli that is prevalent in nondividing cells.

PMID- 2002009
TI  - Expression of two Rhizobium meliloti flagellin genes and their contribution to
      the complex filament structure.
AB  - The complex flagellar filaments of Rhizobium meliloti are composed of two related
      (87% identical) flagellins that are encoded by closely linked, separately
      transcribed genes, flaA and flaB (E. Pleier and R. Schmitt, J. Bacteriol.
      171:1467-1475, 1989). To elucidate the role of the subunits, A and B, in
      assembling the complex filament, the wild-type alleles were replaced with
      defective ones containing a 2,249-bp deletion (accompanied by substitution of a
      kanamycin resistance cartridge), which eliminates 74% of flaA (3' end) and 85% of
      flaB (5' end). The resulting nonmotile, filamentless mutant, RU11011, was tested
      for complementation with wild-type flaA, flaB, and flaA flaB genes provided on
      the multiple-copy vector pRK290. Whereas flaA alone did not restore motility and
      filament production, both flaB and flaA flaB restored 20 to 30% of wild-type
      motility. Apparent causes of this reduced motility were fewer flagella per cell
      and/or shortened filaments sometimes ending in unusually thin, fragile
      structures. Tests with enzyme-linked antiflagellin antibodies indicated that flaA
      is expressed at higher levels than flaB and that multiple copies of flaA lead to
      reduced flagellin export. We conclude that the proximal portion of the complex
      filament is assembled from B subunits (not produced sufficiently to form full
      length flagella) and that the distal portion is made from A subunits. Multiple
      copies of the strong flaA promoter may offset transcriptional controls that
      regulate the synthesis of flagellar structures required for flagellin export.

PMID- 2002010
TI  - Characterization of enzymes of the branched-chain amino acid biosynthetic pathway
      in Methanococcus spp.
AB  - Methanococcus aeolicus, Methanococcus maripaludis, and Methanococcus voltae
      contain similar levels of four enzymes of branched-chain amino acid biosynthesis:
      acetohydroxy acid synthase, acetohydroxy acid isomeroreductase, dihydroxy acid
      dehydratase, and transaminase B. Following growth at low partial pressures of H2
      CO2, the levels of these enzymes in extracts of M. voltae are reduced three- to
      fivefold, which suggests that their synthesis is regulated. The enzymes from M.
      aeolicus were found to be similar to the eubacterial and eucaryotic enzymes with
      respect to molecular weights, pH optima, kinetic properties, and sensitivities to
      O2. The acetohydroxy acid isomeroreductase has a specific requirement for Mg2+,
      and other divalent cations were inhibitory. It was stimulated threefold by K+ and
      NH4+ ions and was able to utilize NADH as well as NADPH. The partially purified
      enzyme was not sensitive to O2. The dihydroxy acid dehydratase is extremely
      sensitive to O2, and it has a half-life under 5% O2 of 6 min at 25 degrees C.
      Divalent cations were required for activity, and Mg2+, Mn2+, Ni2+, Co2+, and Fe2+
      were nearly equally effective. In conclusion, the archaebacterial enzymes are
      functionally homologous to the eubacterial and eucaryotic enzymes, which implies
      that this pathway is very ancient.

PMID- 2002011
TI  - Tandem translation starts in the cheA locus of Escherichia coli.
AB  - The cheA locus of Escherichia coli encodes two protein products, CheAL and CheAS.
      The nucleotide sequences of the wild-type cheA locus and of two nonsense alleles
      confirmed that both proteins are translated in the same reading frame from
      different start points. These start sites were located on the coding sequence by
      direct determination of the amino-terminal sequences of the two CheA proteins.
      Both starts are flanked by inverted repeats that may play a role in regulating
      the relative expression rates of the CheA proteins through alternative mRNA
      secondary structures.

PMID- 2002012
TI  - The genome size of a plant-pathogenic mycoplasmalike organism resembles those of
      animal mycoplasmas.
AB  - The genome size of a mycoplasmalike organism was determined by comparing
      fluorescence intensities of restriction fragments. Its genome size was similar to
      that of Mycoplasma gallisepticum and much smaller than that of Acholeplasma
      laidlawii. Although the genome size is "mycoplasmalike," other molecular data
      indicate a closer evolutionary relationship to A. laidlawii.

PMID- 2002013
TI  - Lipid activation of protein kinase C.

PMID- 2002014
TI  - Self-association of tissue factor as revealed by chemical crosslinking.
AB  - The possible self-association of tissue factor molecules was investigated by
      treating cells expressing tissue factor with bifunctional cross-linking agents.
      The two reagents chosen were 3,3'-dithiobis(sulfosuccinimidylpropionate) and
      sulfosuccinimidyl 2-(p-azidosalicylamido)ethyl-1,3'-dithiopropionate, both of
      which are membrane-impermeable and thiol-cleavable. A human bladder carcinoma
      cell line, J82, and a transfected human kidney cell line expressing high amounts
      of recombinant tissue factor were used in these studies. Exposure of the intact
      cells to the crosslinking reagents was found to result in the formation of
      multimeric tissue factor-containing complexes, the extent of which appeared to be
      dependent upon the amount of tissue factor expressed by the cell. The self
      association of tissue factor was prevented in a variant tissue factor molecule
      harboring a non-homologous transmembrane domain.

PMID- 2002015
TI  - Phosphorylation of eIF-4F by protein kinase C or multipotential S6 kinase
      stimulates protein synthesis at initiation.
AB  - Eukaryotic initiation factor (eIF) 4F, a multiprotein cap binding complex, has
      been shown to be phosphorylated in vivo in response to phorbol 12-myristate 13
      acetate and insulin (Morley, S.J., and Traugh, J.A. (1990) J. Biol. Chem. 264,
      2401-2404; Morley, S.J., and Traugh, J.A. (1990) J. Biol. Chem. 265, 10611
      10616). The effect of phosphorylation on the activity of purified eIF-4F,
      utilizing both protein kinase C and a multifunctional S6 kinase, previously
      identified as protease activated kinase II, has been examined; these protein
      kinases modify eIF-4F p25 and p220 and eIF-4F p220, respectively. Studies with an
      eIF-4F-dependent protein synthesis system showed that phosphorylation of eIF-4F
      with either protein kinase resulted in a 3-5-fold stimulation of translation
      relative to the nonphosphorylated control. Chemical cross-linking of eIF-4F to
      cap-labeled mRNA, showed that phosphorylation increased the interaction of both
      the p25 and p220 subunits of eIF-4F with the 5' end of mRNA. This effect was
      manifested by a stimulation of initiation complex formation as measured by an
      increase in the association of labeled mRNA with 40 S ribosomal subunits in the
      translation system. Thus, phosphorylation of eIF-4F enhances binding to mRNA,
      resulting in a stimulation of protein synthesis at initiation.

PMID- 2002016
TI  - Organization and expression of two tandemly oriented genes encoding
      ribulosebisphosphate carboxylase/oxygenase activase in barley.
AB  - We have isolated and structurally characterized genomic DNA and cDNA sequences
      encoding ribulose-1,5-bisphosphate carboxylase/oxygenase (Rbu-P2 carboxylase)
      activase from barley (Hordeum vulgare L.). Three Rbu-P2 carboxylase activase
      (Rca) polypeptides are encoded in the barley genome by two closely linked,
      tandemly oriented nuclear genes (RcaA and RcaB); cDNAs encoding each of the three
      Rbu-P2 carboxylase activase polypeptides were isolated from cDNA libraries of
      barley leaf mRNA. RcaA produces two mRNAs, which encode polypeptides of 42 and 46
      kDa, by an alternative splicing mechanism identical to that previously reported
      for spinach and Arabidopsis Rca genes (Werneke, J.M., Chatfield, J.M., and Ogren,
      W. L. (1989) Plant Cell 1, 815-825). RcaB is transcribed to produce a single
      mRNA, which encodes a mature peptide of 42 kDa. Genomic Southern blots indicate
      that RcaA and RcaB represent the entire Rbu-P2 carboxylase activase gene family
      in barley. The genes share 80% nucleotide sequence identity, and the 42-kDa
      polypeptides encoded by RcaA and RcaB share 87% amino acid sequence identity.
      Coding regions of the two barley Rca genes are separated by 1 kilobase pair of
      flanking DNA. DNA sequence motifs similar to those thought to control light
      regulated gene expression in other nuclear-encoded plastid polypeptide genes are
      found at the 5' end of both barley Rca genes. Probes specific to three mRNAs were
      used to determine the relative contribution each species makes to the total Rca
      mRNA pool.

PMID- 2002017
TI  - Expression of cloned bovine adrenal rhodanese.
AB  - A cDNA for the enzyme rhodanese (thiosulfate:cyanide sulfurtransferase, EC
      2.8.1.1) has been cloned from a bovine adrenal library. An initiator methionine
      codon precedes the amino-terminal amino acid found in the isolated protein.
      Rhodanese is synthesized in the cytoplasm and transferred to the mitochondrial
      matrix. Thus, any amino-terminal sequence required for organelle import is
      retained in the mature protein. Furthermore, the DNA sequence shows that there
      are three additional amino acids, Gly-Lys-Ala, at the carboxyl terminus that are
      not found by protein sequencing. Additionally, comparison of the published amino
      acid sequence with that encoded by the open reading frame revealed three
      differences in the amino acid sequence. Comparison of the bovine and chicken
      liver sequences shows an overall level of 70% sequence homology, but there is
      complete identity of all residues that have been implicated in the function of
      the enzyme. When two mammalian cells, cos-7 and 293 cells, were transiently
      transfected with a plasmid containing the rhodanese coding region, rhodanese
      activity in lysates increased approximately 20-fold. Fluorograms of denaturing
      polyacrylamide gels detected a large increase in a polypeptide that co-migrated
      with the native protein and reacted with anti-rhodanese antibodies. Nondenaturing
      gels showed two active species that co-migrated with the two major
      electrophoretic forms purified by current procedures. Escherichia coli,
      transformed with a plasmid containing the rhodanese coding region, showed a 15
      fold increase in rhodanese activity over baseline values. When the E. coli
      recombinant protein was analyzed on a nondenaturing gel, only one species was
      observed that co-electrophoresed with the more electropositive variant seen in
      purified bovine liver rhodanese. This single variant could be converted by
      carboxypeptidase B digestion to a form of the enzyme that co-migrated with the
      more electronegative species isolated from bovine liver. Thus, two major,
      enzymatically active electrophoretic variants, commonly observed in mammalian
      cells, can be accounted for by carboxyl-terminal processing without recourse to
      other post-translational modifications.

PMID- 2002018
TI  - Metal-catalyzed oxidation of human serum albumin: conformational and functional
      changes. Implications in protein aging.
AB  - Mild oxidative stress, as elicited by ascorbate, oxygen, and trace metals,
      affects the binding properties of human serum albumin via purely conformational
      changes. In fact, no gross alteration can be observed in the electrophoretic and
      chromatographic patterns of albumin, whereas localized modifications are
      indicated by the changes in absorption and fluorescence spectra and in
      polarization degree. The oxidized protein presents a small increase of bityrosine
      production and a time-dependent increase in the content of carbonyl groups,
      whereas proteolytic susceptibility is unchanged. A higher affinity for cis
      parinaric acid and a slight loss of solubility in high salt indicate a greater
      surface hydrophobicity. Pinpoint denaturation of the albumin molecule is also
      suggested by a decreased "esterase" activity in the presence of p-nitrophenyl
      acetate. Conformational stability evaluated through thermal shock and addition of
      moderate amounts of guanidine indicate that the oxidized protein is more heat
      resistant, less flexible, and more rigid than the native one. Although limited,
      structural damages afforded by the oxidative stress cause alterations of albumin
      binding properties as documented by experiments with probes and physiological
      ligands. The loss of biological activity of human serum albumin induced by
      ascorbate system appears of medical relevance, because it can affect drug
      metabolism and particularly drug tolerance in the elderly.

PMID- 2002019
TI  - Discovery of a metabolic pathway mediating glucose-induced desensitization of the
      glucose transport system. Role of hexosamine biosynthesis in the induction of
      insulin resistance.
AB  - Based on our previous finding that desensitization of the insulin-responsive
      glucose transport system (GTS) requires three components, glucose, insulin, and
      glutamine, we postulated that the routing of incoming glucose through the
      hexosamine biosynthesis pathway plays a key role in the development of insulin
      resistance in primary cultured adipocytes. Two approaches were used to test this
      hypothesis. First, we assessed whether glucose-induced desensitization of the GTS
      could be prevented by glutamine analogs that irreversibly inactivate glutamine
      requiring enzymes, such as glutamine:fructose-6-phosphate amidotransferase (GFAT)
      the first and the rate-limiting enzyme in hexosamine biosynthesis. Both O
      diazoacetyl-L-serine (azaserine) and 6-diazo-5-oxonorleucine inhibited
      desensitization in 18-h treated cells without affecting maximal insulin
      responsiveness in control cells. Moreover, close agreement was seen between the
      ability of azaserine to prevent desensitization of the GTS in intact adipocytes
      (70% inhibition, ED50 = 1.1 microM), its ability to inactivate GFAT in intact
      adipocytes (64% inhibition, ED50 = 1.0 microM) and its ability to inactivate GFAT
      activity in a cytosolic adipocyte preparation (ED50 = 1.3 microM). From these
      results we concluded that a glutamine amidotransferase is involved in the
      induction of insulin resistance. As a second approach, we determined whether
      glucosamine, an agent known to preferentially enter the hexosamine pathway at a
      point distal to enzymatic amidation by GFAT, could induce cellular insulin
      resistance. When adipocytes were exposed to various concentrations of glucosamine
      for 5 h, progressive desensitization of the GTS was observed (ED50 = 0.36 mM)
      that culminated in a 40-50% loss of insulin responsiveness. Moreover, we
      estimated that glucosamine is at least 40 times more potent than glucose in
      mediating desensitization, since glucosamine entered adipocytes at only one
      quarter of the glucose uptake rate, yet induced desensitization at an extra
      cellular dose 10 times lower than glucose. In addition, we found that glucosamine
      induced desensitization did not require glutamine and was unaffected by azaserine
      treatment. Thus, we conclude that glucosamine enters the hexosamine
      desensitization pathway at a point distal to GFAT amidation. Overall, these
      studies indicate that a unique metabolic pathway exists in adipocytes that
      mediates desensitization of the insulin-responsive GTS, and reveal that an early
      step in this pathway involves the conversion of fructose 6-phosphate to
      glucosamine 6-phosphate by the first and rate-limiting enzyme of the hexosamine
      pathway, glutamine:fructose-6-phosphate amidotransferase.

PMID- 2002020
TI  - Demonstration of peptidoglycan-binding sites on lymphocytes and macrophages by
      photoaffinity cross-linking.
AB  - One dominant binding site (70 kDa 6.5 pI protein) for bacterial cell wall
      peptidoglycan (PGN), a macrophage activator and polyclonal B cell mitogen, was
      demonstrated on mouse B and T lymphocytes and macrophages by photoaffinity cross
      linking and two-dimensional polyacrylamide gel electrophoresis. This binding site
      was not present on erythrocytes. The binding was specific for polymeric PGN and
      was competitively inhibited by unlabeled PGN with IC50 = 48 micrograms/ml (0.38
      microM). The binding was partially inhibited by O-acetylated PGN monomers (IC50 =
      469 micrograms/ml, 521 microM), dextran sulfate (IC50 = 1024 micrograms/ml, 124
      microM), and (GlcNAc)3 (IC50 = 6.6 mg/ml, 10 mM), and was not inhibited by non-O
      acetylated PGN monomers and dimers, muramyl dipeptide, PGN pentapeptide, GlcNAc,
      teichoic acid, protein A, and gelatin. The cell surface location of the 70-kDa
      PGN-binding protein was indicated by the ability of PGN to bind to this protein
      in intact metabolically inactive cells (at 4 degrees C and in the presence of
      0.1% NaN3) and by the ability to extract the 70-kDa PGN-binding protein from
      viable B lymphocytes by noncytotoxic concentration of n-octyl-beta-D
      glucopyranoside.

PMID- 2002021
TI  - Peptidoglycan and lipopolysaccharide bind to the same binding site on
      lymphocytes.
AB  - Bacterial cell wall peptidoglycan (PGN) and lipopolysaccharide (LPS), which are
      both macrophage activators and polyclonal B cell mitogens, were shown to bind to
      the same dominant 70-kDa 6.5 pI protein on the surface of mouse B lymphocytes.
      This conclusion was supported by the following results: (a) the PGN- and LPS
      binding proteins co-migrated following photoaffinity cross-linking and two
      dimensional polyacrylamide gel electrophoresis; (b) cross-linking of PGN to this
      70-kDa protein was competitively inhibited by LPS (IC50 = 7.3 microM), LPS from a
      deep rough mutant (IC50 = 6.9 microM), and lipid A (IC50 = 18-72 microM); (c)
      cross-linking of LPS to this 70-kDa protein was competitively inhibited by
      polymeric soluble PGN (IC50 = 0.09 microM) and sonicated high Mr PGN (IC50 = 0.6
      microM); (d) cross-linking of both PGN and LPS to this 70-kDa protein was also
      competitively inhibited by dextran sulfate (IC50 = 115-124 microM); (e) cross
      linking of both PGN and LPS to this 70-kDa protein was inhibited by a (GlcNAc)2
      specific lectin; and (f) peptide maps of the 70-kDa proteins digested with
      chymotrypsin, subtilisin, staphylococcal protease V, or papain were identical for
      PGN- and LPS-binding proteins and unique for each enzyme. Based on competitive
      inhibition experiments, binding of PGN to the 70-kDa protein was 20-1200 times
      stronger than the binding of LPS or lipid A on a per mol basis. However, when
      aggregated micellar structures of LPS or lipid A were considered, the avidities
      of LPS and PGN binding were similar. These results demonstrate binding of PGN and
      LPS to the same 70-kDa protein on lymphocytes and suggest that the binding is
      specific for the (GlcNAc-MurNAc)n backbone of PGN and the (GlcNAc)2 part of lipid
      A.

PMID- 2002022
TI  - Phycobilins of cryptophycean algae. Structures of novel bilins with acryloyl
      substituents from phycoerythrin 566.
AB  - Cryptomonad strain CBD phycoerythrin 566 carries four open-chain tetrapyrrole
      (bilin) prosthetic groups: three singly thioether-linked bilins at alpha-19, beta
      82, and beta-158 and a bilin linked through two thioether bonds at beta-50,61
      (amino acid sequence numbering from Wilbanks, S. M., Wedemayer, G.J., and Glazer,
      A.N. (1989) J. Biol. Chem. 264, 17860-17867). The structures of all four peptide
      linked prosthetic groups were determined by 1H NMR spectroscopy. The bilin at
      beta-82 was identified as phycoerythrobilin (PEB), a common prosthetic group in
      cyanobacterial and red algal phycobiliproteins. The structures of the remaining
      bilins were novel. The bilin at alpha-19, designated Cys-bilin 618, differed from
      PEB in having additional double bonds between C-2 and C-3 of ring A and between C
      12' and C-12", i.e. an acryloyl substituent at C-12 of ring C. The doubly linked
      bilin at beta-50,61 designated DiCys-bilin 584, differed from doubly linked PEB
      (Schoenleber, R.W., Lundell, D.J., Glazer, A.N., and Rapoport, H. (1984) J. Biol.
      Chem. 259, 5481-5484) in possessing an acryloyl substituent at C-12 of ring C in
      place of a propionyl substituent. Similarly, the bilin at beta-158, designated
      Cys-bilin 584, differed from singly-linked PEB in possessing an acryloyl
      substituent at C-12 of ring C in place of a propionyl substituent. The three
      novel cryptomonad bilins join heme d1 and chlorophylls c1, c2, and c3 as the only
      known porphyrin-derived natural products with acryloyl substituents.

PMID- 2002023
TI  - Identification of a prominent 85-kDa cAMP-dependent phosphoprotein associated
      with late G1 phase in mitogen-stimulated B lymphocytes.
AB  - In order to elucidate late regulatory events which may be involved in the onset
      of S phase in B lymphocytes, we studied the effect of anti-Ig on phosphorylation
      of soluble proteins at late G1 phase. Stimulation of murine splenic B lymphocytes
      with anti-Ig and other mitogens for 18 h was found to be associated with a major
      increase in phosphorylation of an 85 kDa/pI approximately 5.3 cytosolic protein,
      conversely, stimulation of the cells with non-mitogenic stimuli did not induce
      the phosphorylation of pp85. The increase in phosphorylation of pp85 could not be
      detected after 30 min, was barely detectable after 6 h, but was very prominent
      after 18 h of stimulation with anti-Ig. Thus, the increase in phosphorylation of
      pp85 is not an early signal but is rather correlated with the late G1 phase. pp85
      could not be detected in the nuclei of either control or stimulated cells.
      Stimulation of B cells for 30 min with forskolin induced the phosphorylation of
      pp85, while phorbol ester did not have any effect. The phosphorylation of pp85
      was induced by the catalytic subunit of cAMP protein kinase. Comparison of the
      phosphopeptide map of pp85 phosphorylated by anti-Ig in intact cells to the
      phosphopeptide map phosphorylated by forskolin or by the catalytic subunit of
      cAMP protein kinase, showed a striking similarity indicating that cAMP protein
      kinase may be involved in phosphorylation of pp85 in mitogen-stimulated cells. An
      increase in intracellular cAMP levels at late G1 phase was found in B cells
      stimulated by mitogens. These results implicate an important role for cAMP
      dependent phosphorylation events, specifically the phosphorylation of pp85/pI
      5.3, at late G1 phase during the cell cycle.

PMID- 2002024
TI  - Structural and functional comparison of type IX collagen-proteoglycan from
      chicken cartilage and vitreous humor.
AB  - Type IX collagen-proteoglycan is a major component of hyaline cartilages where it
      is located on the surface of the collagen fibrils so that a collagenous domain of
      the molecule (called COL3) and a non-collagenous domain (called NC4) project at
      periodic distances away from the surface of the fibril. Type IX collagen
      proteoglycan is also present on the surface of the collagen fibrils of the adult
      chicken vitreous but, unlike cartilage, lacks the NC4 domain and possesses a very
      long chondroitin sulfate chain which provides an extensive coat to the fibril. A
      monoclonal antibody (called 4D6) is described which will distinguish cartilage
      from vitreous type IX collagen. To form the epitope for 4D6 two peptides called
      C2 and C5 derived, respectively, from the alpha 1(IX) and alpha 3(IX) chains are
      required. Further analysis shows that specificity for 4D6 resides only in the C2
      peptide from cartilage and not in C5. These results are entirely consistent with
      recent evidence that there are two promoters for transcription of the alpha 1(IX)
      chain which will result in an alpha 1(IX) chain in which the NC4 domain is either
      present or absent and that expression of these two promoters has tissue
      specificity (Nishimura, I., Muragaki, Y., and Olsen, B. R. (1989) J. Biol. Chem.
      264, 20033-20041). In addition, the function of type IX collagen in cartilage and
      vitreous may differ with the long chondroitin sulfate chains of vitreous type IX
      collagen being responsible for the gel-like matrix of this tissue.

PMID- 2002025
TI  - Assembly and secretion of recombinant human fibrinogen.
AB  - Expression vectors containing full-length cDNAs for each of the human fibrinogen
      chains were constructed. COS-1 cells were transfected with single vectors,
      mixtures of two, or with all three vectors and stable cell lines selected. Cells
      transfected with single vectors, or with mixtures of any two vectors, expressed
      the appropriate fibrinogen chains but did not secrete them. COS cells transfected
      with three vectors expressed all of the chains and secreted fibrinogen. COS cells
      transfected with three vectors contained, intracellularly, a mixture of
      fibrinogen-related proteins. The four main intracellular products were nascent
      fibrinogen, an A alpha.gamma complex, free A alpha chains, and free gamma chains.
      This is a similar pattern to that noted in Hep G2 cells. The intracellular forms
      of fibrinogen were sensitive to endoglycosidase H, indicating that they reside in
      a pre-Golgi compartment. Secreted fibrinogen was endoglycosidase H-insensitive,
      suggesting that the secreted glycoprotein moieties were processed in the normal
      manner. When mixed with plasma fibrinogen, radiolabeled recombinant fibrinogen
      was incorporated into a thrombin-induced clot. These studies demonstrate that COS
      cells transfected with all three fibrinogen chain cDNAs are capable of assembling
      and secreting a functional fibrinogen molecule.

PMID- 2002026
TI  - G protein regulation of phospholipase C activity in a membrane-solubilized system
      occurs through a Mg2(+)- and time-dependent mechanism.
AB  - GTP-binding proteins have been implicated to function as key transducing elements
      in the mechanism underlying receptor activation of a membrane-associated
      phospholipase C activity. In the present study, the regulation of phospholipase C
      activity by GTP-binding proteins has been characterized in a detergent
      solubilized system derived from bovine brain membranes. Guanosine-5'-(3-O
      thio)triphosphate (GTP-gamma-S) and guanyl-5'-yl imidodiphosphate (Gpp(NH)p)
      stimulated a dose-dependent increase in phospholipase C activity with half
      maximal activation at 0.6 microM and 10 microM, respectively. The maximal degree
      of stimulation due to Gpp(NH)p or GTP-gamma-S was comparable. 100 microM GTP had
      only a slight stimulatory effect on phospholipase C activity. Adenine
      nucleotides, 100 microM adenylyl-imidodiphosphate and ATP, did not stimulate
      phospholipase C activity, indicating that specific guanine nucleotide-dependent
      regulation of phospholipase C activity was preserved in the solubilized state.
      Gpp(NH)p or GTP-gamma-S stimulation of phospholipase C activity was time
      dependent and required Mg2+.Mg2+ regulated the time course for activation of
      phospholipase C by guanine nucleotides and the ability of guanine nucleotides to
      promote an increase in the Ca2+ sensitivity of phospholipase C. 200 microM GDP
      beta-S or 5 mM EDTA rapidly reversed the activation due to GTP-gamma-S or
      Gpp(NH)p. These findings demonstrate that G protein regulation of phospholipase C
      activity in a bovine brain membrane- solubilized system occurs through a Mg2+ and
      time-dependent mechanism. Activation is readily reversible upon addition of
      excess GDP-beta-S or removal of Mg2+.

PMID- 2002027
TI  - 77Se NMR characterization of 77Se-labeled ovine erythrocyte glutathione
      peroxidase.
AB  - Lambs, maintained on a selenium-deficient diet supplemented with 94 atom % Na2
      27SeO3, have been used as a source of 77Se-enriched erythrocyte glutathione
      peroxidase. After 5 months on this diet, the percentage of selenium in the enzyme
      derived from the supplement had reached 88%. From each monthly bleeding of two
      sheep, approximately 20 mg of 77Se-enriched glutathione peroxidase could be
      isolated in pure form. Although attempts to observe 77Se NMR signals from the
      native enzyme labeled with 6,6'-[77Se]diselenobis-(3-nitrobenzoic acid) failed,
      due to the low solubility of the enzyme, two 77Se resonances were observed after
      unfolding the enzyme with 8 M urea and reaction with iodoacetamide. These
      resonances, at 195 and 377 ppm, were from the selenoether alkylamide derivative
      and from protein cross-linked selenide sulfide species, respectively. Relaxation
      time measurements on the selenoether at 4.7 and 9.4 teslas enabled an estimate of
      the chemical shift anisotropy to be made. A value of less than or equal to 262
      ppm was determined. Reduction of the denatured selenide sulfide species with
      dithiothreitol gave an observable 77Se resonance from the Se- moiety at pH 8 and
      from SeH at pH 4.2. The chemical form of the selenocysteine residue in the
      resting state enzyme most consistent with formation of the acetamide derivative
      and the selenide sulfide is Se- or SeH. From the magnitudes of the estimated
      chemical shift anisotropies, it is predicted that direct observation of selenium
      in the native enzyme will be feasible if the enzyme concentration can be
      increased to 0.25 mM tetrameric glutathione peroxidase.

PMID- 2002028
TI  - Ligand-binding characteristics of rat serum-type mannose-binding protein (MBP-A).
      Homology of binding site architecture with mammalian and chicken hepatic lectins.
AB  - Sugar-binding characteristics of rat serum mannose-binding protein (MBP) were
      studied using the carbohydrate-recognition domain of this protein expressed from
      a cloned cDNA. To assess the binding affinity of various test compounds, they
      were added as inhibitors in a binding assay in which 125I-MBP was incubated with
      yeast cells and the extent of binding was estimated from the radioactivity
      associated with the pelleted cells. The results of such inhibition assays suggest
      that MBP has a small binding site which is probably of the trough-type. The 3-
      and 4-OH of the target sugar are indispensable, while the 6-OH is not required.
      These characteristics are shared by the rat hepatic lectin and chicken hepatic
      lectin, both of which are C-type lectins containing carbohydrate-recognition
      domains highly homologous to that of MBP. Apparently, the related primary
      structures of these lectins give rise to similar gross architecture of their
      binding sites, despite the fact that each exhibits different sugar binding
      specificities.

PMID- 2002029
TI  - Purification and characterization of peroxisomal L-pipecolic acid oxidase from
      monkey liver.
AB  - L-Pipecolic acid oxidase has been purified to near homogeneity from Rhesus monkey
      liver. The protein, a yellow monomer, has a molecular weight of 46,000 by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis and a pI of 8.9. It contains a
      covalently bound flavin with absorption maxima at 457 and 383 nm and a shoulder
      at 480 nm. The purified enzyme is most reactive toward L-pipecolic acid, with
      lesser reactivities toward L-proline and sarcosine. The enzyme has no significant
      reactivity toward the D-enantiomer of pipecolic acid or toward any other amino
      acid tested. Benzoic acid is a competitive inhibitor of the enzyme with a Ki of
      750 microM. The Km of the purified enzyme is 3.7 mM for L-pipecolic acid. With
      less purified preparations, the reaction product is alpha-aminodipic acid. The
      purified enzyme, however, produces an intermediate which reacts with ortho
      aminobenzaldehyde to form an alpha-aminoadipic acid semialdehyde adduct. Thus,
      the formation of alpha-aminoadipic acid requires at least two enzymes.

PMID- 2002030
TI  - Purification and characterization of a rat liver membrane tyrosine-protein
      kinase, the possible protooncogene c-yes product, p60c-yes.
AB  - A tyrosine-protein kinase was purified more than 270-fold from the rat liver
      plasma membrane fraction by successive column chromatographies on Sephacryl S
      300, wheat germ agglutinin-agarose, casein-Sepharose, and hydroxylapatite,
      followed by isoelectrofocusing electrophoresis. The enzyme with pI of 6.2 was a
      60-kDa single polypeptide which represented 42% of total protein. The enzyme
      reacted quantitatively with a monoclonal antibody to the amino-terminal sequence
      (Cys-3 to Ser-66) specific to the human c-yes protein, but not with antibodies to
      the specific amino-terminal sequences of the c-src, fyn, and lck proteins. The
      purified enzyme contained almost no phosphotyrosine residue but was
      autophosphorylated with Mg.ATP exclusively at tyrosine residues with concomitant
      increase in the kinase activity. The rates of autophosphorylation of the enzyme
      and phosphorylation of tyrosine-glutamate (1:4) copolymers, catalyzed by the
      enzyme were proportional to the square of enzyme concentration, suggesting that
      p60c-yes undergoes autophosphorylation through intermolecular catalysis,
      resulting in stimulation of the enzyme activity. Although the enzyme reaction
      showed an essential requirement for Mg2+ or Mn2+ with optimal concentrations of
      20 and 3 mM, respectively, autophosphorylation significantly activated the enzyme
      only in the presence of Mg2+. Autophosphorylation of the enzyme reduced the Km
      for tyrosine-glutamate copolymers and tubulin, but not for ATP, and increased the
      Vmax of copolymer and tubulin phosphorylation.

PMID- 2002031
TI  - Pasteurella multocida toxin, a potent mitogen, increases inositol 1,4,5
      trisphosphate and mobilizes Ca2+ in Swiss 3T3 cells.
AB  - Pasteurella multocida toxin, both native and recombinant, is an extremely potent
      mitogen for Swiss 3T3 cells and acts to enhance the formation of total inositol
      phosphates (Rozengurt, E., Higgins, T., Changer, N., Lax, A.J., and Staddon, J.M.
      (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 123-127). P. multocida toxin also
      stimulates diacylglycerol production and activates protein kinase C (Staddon,
      J.M., Chanter, N., Lax, A.J., Higgins, T.E., and Rozengurt, E. (1990) J. Biol.
      Chem. 265, 11841-11848). Here we analyze, by [3H]inositol labeling and high
      performance liquid chromatography, the inositol phosphates in recombinant P.
      multocida toxin-treated cells. Recombinant P. multocida toxin stimulated
      increases in [3H]inositol 1,4,5-trisphosphate ([3H]Ins(1,4,5)P3) and its
      metabolic products, including Ins(1,3,4,5)P4, Ins(1,3,4)P3, Ins(1,4)P2,
      Ins(4/5)P, and Ins(1/3)P. The profile of the increase in the cellular content of
      these distinct inositol phosphates was very similar to that elicited by bombesin.
      Furthermore, recombinant P. multocida toxin, like bombesin, mobilizes an
      intracellular pool of Ca2+. Recombinant P. multocida toxin pretreatment greatly
      reduces the Ca2(+)-mobilizing action of bombesin, consistent with Ca2+
      mobilization from a common pool by the two agents. The enhancement of inositol
      phosphates and mobilization of Ca2+ by recombinant P. multocida toxin were
      blocked by the lysosomotrophic agents methylamine, ammonium chloride, and
      chloroquine and occurred after a dose-dependent lag period. The stimulation of
      inositol phosphate production by recombinant P. multocida toxin persisted after
      removal of extracellular toxin, in contrast to the reversibility of the action of
      bombesin. Recombinant P. multocida toxin, unlike bombesin and guanosine 5'-O
      (gamma-thiotriphosphate), did not cause the release of inositol phosphates in
      permeabilized cells. These data demonstrate that recombinant P. multocida toxin,
      acting intracellularly, stimulates the phospholipase C-mediated hydrolysis of
      phosphatidylinositol 4,5-bisphosphate.

PMID- 2002032
TI  - Hepatic lipase hydrolysis of lipid monolayers. Regulation by apolipoproteins.
AB  - A monolayer technique was used to study the substrate specificity of hepatic
      lipase (HL) and the effect of surface pressure and apolipoproteins on hydrolysis
      of lipid monolayers by this enzyme. HL hydrolyzed readily
      phosphatidylethanolamine monolayers. Pure trioctanoylglycerol was found to be a
      poor substrate but when progressively diluted with nonhydrolyzable 1,2
      didodecanoylphosphatidylcholine hydrolysis of triacylglycerol by HL reached
      maximum at a molar ratio of 1:1 triacylglycerol to phosphatidylcholine. The
      activation of triacylglycerol hydrolysis was not due to altered penetration of
      HL. The surface pressure optimum of HL for the hydrolysis of
      phosphatidylethanolamine monolayers was broad between 12.5 and 25 mN/m. When
      apolipoprotein E was injected beneath the monolayer of phosphatidylethanolamine
      prior to enzyme addition, a 3-fold activation of HL was observed at surface
      pressures equal to or below 15 mN/m. Below surface pressures of 20 mN/m
      apolipoprotein E did not affect the penetration of HL into the lipid-water
      interface. Apolipoprotein E slightly activated the hydrolysis of triacylglycerol
      by HL at 10 mN/m. At a high surface pressure of 25 mN/m all apolipoproteins
      tested (apolipoproteins A-I, A-II, C-I, C-II, C-III, and E) inhibited the
      penetration into and HL activity on phosphatidylethanolamine At 18.5 mN/m all
      apolipoproteins except apolipoprotein E inhibited the hydrolysis of
      triacylglycerol in the triacylglycerol:phosphatidylcholine mixed film. Based on
      these results we present a hypothesis that phospholipid present in apolipoprotein
      E-rich high density lipoprotein-1 and triacylglycerol in intermediate density
      lipoprotein would be preferred substrates for HL.

PMID- 2002033
TI  - The structural homology of amicyanin from Thiobacillus versutus to plant
      plastocyanins.
AB  - The complete amino acid sequence of the blue copper protein amicyanin of
      Thiobacillus versutus, induced when the bacterium is grown on methylamine, has
      been determined as follows:
      QDKITVTSEKPVAAADVPADAVVVGIEKMKYLTPEVTIKAGETVYWVNGEVMPHNVA
      FKKGIVGEDAFRGEMMTKDQAYAITFNEAGSYDYFCTPHPFMRGKVIVE. The four copper ligand
      residues in this 106-residue-containing polypeptide chain are His54, Cys93,
      His96, and Met99. The Thiobacillus amicyanin is 52% similar to the amicyanin of
      Pseudomonas AM1, the only other copper protein known with the same spacing
      between the second histidine ligand and the methionine ligand. T. versutus
      amicyanin contains no cysteine bridge and is more closely related to the plant
      copper protein plastocyanin than to the bacterial copper protein azurin.
      Alignment of the two known amicyanin sequences with the consensus sequence of the
      plastocyanins and comparison with the known three-dimensional structure of poplar
      leaves plastocyanin reveals that the bacterial proteins have the same overall
      structure with two beta-sheets packed face to face. The major structural
      differences between the amicyanins and the plastocyanins appear to be located in
      two of the five loops that connect the six identified beta-strands of the
      amicyanins. The first of these two loops, connecting strands F and G, contains a
      ligand histidine and must have a different conformation from the same loop in the
      plastocyanins because it is shorter by two amino acids. Further differences occur
      in the loop connecting the strands D and E. This loop contains only 17 residues
      in amicyanin whereas the corresponding loop of plastocyanin contains 25 residues.
      Despite these differences the amicyanins appear much closer related to the
      plastocyanins than to the azurins. The present findings demonstrate that the
      occurrence of blue copper proteins with clearly plastocyanin-like features is not
      restricted to photosynthetic redox chains.

PMID- 2002034
TI  - Proofreading activity of DNA polymerase III responds like elongation activity to
      auxiliary subunits.
AB  - A comparison of the 3'----5' proofreading properties between Escherichia coli DNA
      polymerase III holoenzyme and DNA polymerase III' was conducted. This study
      indicated that the influence of the holoenzyme auxiliary subunits on the
      proofreading exonuclease parallels their effect on the elongation reaction. At
      physiological ionic strengths the auxiliary subunits markedly stimulated the
      exonuclease rate in an ATP-dependent reaction, while the exonuclease rate of DNA
      polymerase III' was not affected by ATP. E. coli single-stranded DNA binding
      protein stimulated the 3'----5' exonuclease activity of holoenzyme and inhibited
      DNA polymerase III'. Similarly, the auxiliary subunits and ATP converted the
      proofreading activity to a highly processive exonuclease. Our observation, that
      the exonuclease activity of the DNA polymerase III holoenzyme responded to ATP,
      salt, and E. coli single-stranded DNA-binding protein like the elongation
      activity, is consistent with the polymerase and exonuclease subunits acting
      within the same complex in a coordinated reaction.

PMID- 2002035
TI  - The characterization of a complex of three bacteriophage T4 recombination
      proteins, uvsX protein, uvsY protein, and gene 32 protein, on single-stranded
      DNA.
AB  - Three recombination proteins of bacteriophage T4, uvsX, uvsY, and gene 32
      proteins, were examined for the formation of a complex with short single-stranded
      DNA (ssDNA) molecules containing either 24 or 69 nucleotides. Gel-shift assays
      revealed that either the uvsX or uvsY protein, when present alone, formed a
      stable complex only with the 69-mer, while the gene 32 protein bound stably to
      both ssDNAs. However, a characteristic stable complex formed on the 24-mer when
      both the uvsX and uvsY proteins were present, and the uvsY protein bound to this
      DNA in the presence of the gene 32 protein. Isolation of the complexes by
      centrifugation through a glycerol gradient revealed their protein constituents
      and showed that the uvsX protein-uvsY protein-24-mer ssDNA complex formed even in
      the presence of excess gene 32 protein. The possible biological significance of
      these protein-DNA complexes is discussed.

PMID- 2002036
TI  - Oxidation of molybdopterin in sulfite oxidase by ferricyanide. Effect on electron
      transfer activities.
AB  - The attenuation of the sulfite:cytochrome c activity of sulfite oxidase upon
      treatment with ferricyanide was demonstrated to be the result of oxidation of the
      pterin ring of the molybdenum cofactor in the enzyme. Oxidation of molybdopterin
      (MPT) was detected in several ways. Ferricyanide treatment not only abolished the
      ability of sulfite oxidase to serve as a source of MPT to reconstitute the
      aponitrate reductase in extracts of the Neurospora crassa mutant nit-1 but also
      eliminated the ability of sulfite oxidase to reduce dichlorobenzenoneindophenol
      after anaerobic denaturation. Additionally, the absorption spectrum of
      anaerobically denatured ferricyanide-treated molybdenum fragment of rat liver
      sulfite oxidase was typical of fully oxidized pterins. Ferricyanide treatment had
      no effect on the protein of sulfite oxidase or on the sulfhydryl-containing side
      chain of MPT. Quantitation of the ferricyanide reaction showed that 2 mol of
      ferricyanide were reduced per mol of MPT oxidized, yielding a fully oxidized
      pterin. These results corroborate the previously reported conclusion that the
      native state of reduction of MPT in sulfite oxidase is at the dihydro level
      (Gardlik, S., and Rajagopalan, K.V. (1990) J. Biol. Chem. 265, 13047-13054). As a
      result of oxidation of the pterin ring, the affinity of MPT for molybdenum is
      decreased, leading to eventual loss of molybdenum. Because the loss of molybdenum
      is slow, a population of sulfite oxidase molecules can exist in which molybdenum
      is complexed to oxidized MPT. These molecules retain sulfite:O2 activity, a
      function apparently dependent solely on the molybdenum-thiolate complex, yet have
      greatly decreased sulfite:cytochrome c activity, a function requiring heme as
      well as the molybdenum center of holoenzyme. These observations suggest that the
      pterin ring of MPT participates in enzyme function, possibly in electron
      transfer, directly in catalysis, or by controlling the oxidation/reduction
      potential of molybdenum.

PMID- 2002037
TI  - Thiocyanate is the major substrate for eosinophil peroxidase in physiologic
      fluids. Implications for cytotoxicity.
AB  - The potent cytotoxic capacity of eosinophils for parasites and host tissue has in
      part been attributed to the catalytic action of eosinophil peroxidase (EPO),
      which preferentially oxidizes Br- to the powerful bleaching oxidant HOBr in
      buffers that mimic serum halide composition (100 mM Cl-, 20-100 microM Br-, less
      than 1 microM I-). However, serum also contains 20-120 microM SCN-, a
      pseudohalide whose peroxidative product, HOSCN, is a weak, primarily sulfhydryl
      reactive oxidant. Because of its relative abundance and high oxidation potential,
      we hypothesized that SCN-, not Br- or I-, is the major substrate for EPO in
      physiologic fluids. We find that in Earle's buffer (100 mM Cl-) supplemented with
      100 microM Br- and varying concentrations of SCN-, HOBr production by activated
      eosinophils and purified EPO, assayed by conversion of fluorescein to
      dibromofluorescein, was 50% inhibited (ID50) by only 1 microM SCN-. SCN- also
      blocked (ID50 10 microM) EPO oxidation of I- to HOI, assayed as iodofluorescein,
      despite the presence of 100 microM (i.e. grossly supraphysiologic) I-.
      Thionitrobenzoic acid oxidation kinetics indicate that SCN- is the initial
      species oxidized by EPO in equimolar mixtures of SCN- and Br- and in human serum.
      EPO also catalyzed the covalent incorporation of [14C]SCN- into proteins in
      buffers regardless of Br- concentration and in human serum. Comparing the
      cytotoxicity of HOSCN and HOBr for host cells, we find that even subphysiologic
      concentrations of SCN- (3.3-10 microM) nearly completely abrogate the potent Br(
      )-dependent toxicity of EPO for 51Cr-labeled aortic endothelial cells and
      isolated working rat hearts, recently developed models of eosinophilic
      endocarditis. Thus, HOSCN, hitherto best known as a bacteriostatic agent in
      saliva and milk, is likely also the major oxidant produced by EPO in physiologic
      fluids, and the presence of SCN- averts damage to EPO-coated host tissues that
      might otherwise accrue as a result of HOBr generation. In view of these findings,
      the potential role of HOSCN in eosinophil killing of parasitic pathogens deserves
      close examination.

PMID- 2002038
TI  - Isolation and sequence determination of cDNA encoding T-protein of the glycine
      cleavage system.
AB  - T-protein is a component of the glycine cleavage system and catalyzes the
      tetrahydrofolate-dependent reaction. A partial cDNA for chicken T-protein was
      isolated by screening a chicken liver cDNA library with oligonucleotide probes
      based on amino acid sequences. The clone (CT5C) contains a 675-base pair insert
      encoding the C-terminal half of the T-protein. Screening of a bovine liver lambda
      gt10 cDNA library with the insert of CT5C as a probe detected a clone, BT5A, with
      an insert of about 2 kilobase pairs. The 1191-base pair coding region encodes a
      precursor protein of 397 amino acids (Mr 42,852) comprised of a 22-residue
      mitochondrial targeting sequence and a 375-residue mature protein (Mr 40,534).
      The 33 amino acids immediately following the targeting sequence correspond
      exactly to those determined by sequence analysis of the amino terminus of the
      purified bovine T-protein. The mature protein contains several hydrophilic
      segments with a cluster of arginine and lysine. The T-protein cDNA probe
      hybridized to an mRNA species of about 2 kilobases in bovine brain, lung, heart,
      and liver. A probe for H-protein hybridized with two species of mRNA in these
      tissues and weak signals were also found in spleen. Although the enzymatic
      activities of T-protein and H-protein were found in these tissues where
      transcripts were found, activity of P-protein was detected only in liver and
      brain. Southern blot analysis of genomic DNA suggested that T-protein is a single
      copy gene.

PMID- 2002039
TI  - Formation of novel C21-bile acids from cholesterol in the rat. Structure
      identification of the major Di- and trihydroxylated species.
AB  - We recently showed that previously unknown di- and trihydroxylated C21-bile acids
      are major degradation products of sitosterol and campesterol in bile-fistulated
      female Wistar rats. Using a mixture of 4-14C- and 22-3H-labeled cholesterol it
      was shown that such C21-bile acids are formed also from cholesterol in amounts up
      to about 25% of the total formation of bile acids. The C21-bile acids were formed
      from labeled cholesterol also in perfused rat liver, demonstrating that the liver
      is the site of synthesis. The major trihydroxylated C21-bile acids in bile were
      identified, by means of mass spectrometry, NMR, stereospecific dehydrogenases,
      and reagents, as 5 beta-pregnan-3 alpha, 11 beta, 15 beta-triol-21-oic acid and 5
      beta-pregnan-3 alpha, 11 beta, 15 alpha-triol-21-oic acid. The corresponding 11
      oxo-isomers were also present. A minor trihydroxylated C21-bile acid was
      identified as 5 beta-pregnan-3 alpha, 11 beta, 16-triol-21-oic acid. The major
      dihydroxylated C21-bile acid was identified by the same means as 5 alpha-pregnan
      3 alpha, 12 alpha-diol-21-oic acid. Male rats converted 4-14C-cholesterol into
      C21-bile acids less efficiently than did female rats. None of the C21-bile acids
      from male rats contained a 15-hydroxyl group. It is speculated that the novel C21
      bile acids are formed both from cholesterol and from plant sterols by an initial
      hydroxylation at C21 followed by peroxisomal or mitochondrial beta-oxidation. The
      presence of a hydroxyl group at C15 may facilitate this reaction. The above
      formation of C21-bile acids shows that mammalian liver is able to degrade the
      side chain of cholesterol beyond the C24 stage, even in the absence of a blocking
      group at C24. C21-bile acids, or one of their precursors, are hydroxylated in the
      liver by a hitherto unknown 11 beta-hydroxylase. The possible physiological
      importance of the C21-bile acids is discussed.

PMID- 2002040
TI  - Bradykinin-induced oscillations of cell membrane potential in cells expressing
      the Ha-ras oncogene.
AB  - Products of ras genes are putative elements of growth factor signal transduction.
      However, the mechanism of action of these proteins in normal and malignant growth
      is as yet obscure. To test for functional consequences of ras oncogene
      expression, electrophysiological experiments were performed on NIH-3T3
      fibroblasts transfected with a transforming Ha-ras MMTV-LTR construct expressing
      the oncogene on treatment with dexamethasone (+ras). Transfected cells in the
      absence of dexamethasone (-ras) and nontransfected cells in the presence of
      dexamethasone (oras) served as controls. In -ras and oras, bradykinin induces a
      single, transient hyperpolarization. In +ras, bradykinin elicits oscillations of
      cell membrane potential throughout the presence of the hormone by activation of
      calcium-sensitive K+ channels. The oscillations of cell membrane potential are
      abolished in the absence of extracellular calcium. As evident from fura 2
      fluorescence, bradykinin leads to a transient increase of intracellular calcium
      both in the presence and absence of extracellular calcium. Oscillations of
      intracellular calcium could be observed in +ras cells, if bradykinin was applied
      at reduced extracellular sodium concentration possibly to impair calcium
      extrusion via the sodium/calcium exchange. Bradykinin induces oscillations of
      cell membrane potential similarly in -ras cells loaded with GTP[S], a
      nonhydrolyzable analogue of GTP. Thus, the altered response of ras oncogene
      expressing cells to bradykinin relates to the GTP binding property of the ras
      protein. It is concluded that in cells expressing ras oncogene but not in other
      fibroblasts bradykinin mimicks the effect of growth factors on the cell membrane.

PMID- 2002041
TI  - The 90-kDa heat shock protein (hsp-90) possesses an ATP binding site and
      autophosphorylating activity.
AB  - The 90-kDa heat shock protein (hsp-90) is an abundant cytosolic protein believed
      to play a role in maintenance of protein trafficking and closely associated with
      several steroid hormone receptors. Incubation of highly purified hsp-90 with
      [gamma-32P]ATP results in its autophosphorylation on serine residues. There are
      several lines of evidence which suggest that this activity is due to a kinase
      intrinsic to hsp-90 rather than some closely associated protein kinases: 1) the
      phosphorylation persists after the removal of casein kinase II by heparin
      chromatography and after immunoprecipitation of hsp-90 with anti-hsp-90
      antibodies. 2) The approximate kM for ATP of the reaction is 0.16 mM, higher than
      that of many other protein kinases. 3) Phosphorylation is not affected by a
      number of activators and inhibitors of other known kinases which might associate
      with hsp-90. 4) The phosphorylation displays a unique cation dependence being
      most active in the presence of Ca2+ and practically inactive with Mg2+, although
      the autophosphorylation in the presence of Mg2+ is activated by histones and
      polyamines. 5) The activity is remarkably heat-stable; incubation of hsp-90 for
      20 min at 95 degrees C results in only a 60% decrease in autophosphorylation. 6)
      Finally, and most importantly, purified hsp-90 can be labeled with azido-ATP and
      it is able to bind to ATP-agarose. The binding shows similar cation dependence to
      the autophosphorylation. These data are in agreement with the presence of a
      consensus sequence for ATP binding sites in the primary structure of the protein
      similar to that observed in the 70-kDa heat-shock proteins. Our data suggest the
      90-kDa heat shock protein possesses an enzymatic activity analogous in many
      respects to the similar activity of the 70-kDa heat shock proteins. This may
      represent an important, previously unrecognized function of hsp-90.

PMID- 2002042
TI  - Phosphorylation-dependent binding of a synthetic MARCKS peptide to calmodulin.
AB  - A 25-amino acid peptide, containing the four protein kinase C (PKC)
      phosphorylation sites and the calmodulin (CaM) binding domain of the
      myristoylated alanine-rich C kinase substrate (MARCKS) protein, has been
      synthesized and used to determine the effects of phosphorylation on its binding
      and regulation of CaM. PKC phosphorylation of this peptide (3.0 mol of Pi/mol of
      peptide) produced a 200-fold decrease in its affinity for CaM. PKC
      phosphorylation of the peptide resulted in its dissociation from CaM over a time
      course that paralleled the phosphorylation of 1 mol of serine/mol of peptide. The
      peptide inhibited CaM's binding to myosin light chain kinase and CaM's
      stimulation of phosphodiesterase and calcineurin. PKC phosphorylation of the
      peptide resulted in a rapid release of bound CaM, allowing its subsequent binding
      to myosin light chain kinase (t1/2 = 1.6 min), stimulation of phosphodiesterase
      (t1/2 = 1.2 min) and calcineurin (t1/2 = 1.7 min). Partially purified MARCKS
      protein produced a similar inhibition of CaM-phosphodiesterase which was reversed
      by PKC phosphorylation. PKC phosphorylation of the peptide occurred primarily at
      serine 8 and serine 12, and phosphorylation of serine 12 regulated peptide
      affinity for CaM. Thus, PKC phosphorylation of the peptide and the MARCKS protein
      results in the rapid release of CaM and the subsequent activation of CaM
      dependent enzymes. This process might allow for interplay between PKC and CaM
      dependent signal transduction pathways.

PMID- 2002043
TI  - Principal neurofilament-associated protein kinase in squid axoplasm is related to
      casein kinase I.
AB  - A cytoskeletal extract of pure axoplasm, highly enriched with neurofilaments
      (ANF), was prepared from the giant axon of the squid. This ANF preparation also
      contained potent kinase activities which phosphorylated the Mr greater than
      400,000 (high molecular weight) and Mr 220,000 squid neurofilament protein
      subunits. High salt (1 M) extraction of this ANF preparation solubilized most of
      the neurofilament proteins and kinase activities and gel filtration on an AcA 44
      column separated these two components. The neurofilaments eluted in the void
      volume of the column while the kinase activities eluted in the 17-44-kDa range of
      the column. Two major kinase activities were measured in this peak of activity.
      One of these strongly phosphorylated the phosphate acceptor peptide Leu-Arg-Arg
      Ala-Ser-Leu-Gly (Kemptide) and was completely inhibited by the selective
      inhibitor of cAMP-dependent kinase Thr-Thr-Tyr-Ala-Asp-Phe-Ile-Ala-Ser-Gly-Arg
      Thr-Gly-Arg-Arg-Asn-Ala-Ile- NH2 (Wiptide). Since addition of cAMP did not
      stimulate activity, this suggested that this kinase was a free catalytic subunit
      of cAMP-dependent kinase associated with the neurofilaments. The second kinase
      activity most effectively phosphorylated alpha-casein, and this activity was not
      affected by Wiptide. The alpha-casein phosphorylating activity (ANF kinase) was
      the principal activity responsible for neurofilament protein phosphorylation, and
      was not inhibited by various inhibitors against second messenger regulated
      kinases, suggesting it was related to the casein kinase family. Four lines of
      evidence indicate ANF kinase was similar to casein kinase I. These were: 1) the
      apparent molecular weight determined by gel filtration and the chromatographic
      elution profile on phosphocellulose column corresponded to casein kinase I; 2)
      heparin, an inhibitor of casein kinase II at 2-5 micrograms/ml, stimulated both
      ANF kinase and purified casein kinase I at these concentrations, while CKI-7, a
      relatively selective inhibitor of casein kinase I, inhibited ANF kinase in a
      comparable dose-response fashion; 3) purified casein kinase I strongly
      phosphorylated both ANF protein subunits (like ANF kinase) whereas casein kinase
      II was relatively ineffective; and 4) tryptic peptide maps of the HMW and Mr
      220,000 neurofilament proteins after phosphorylation by ANF kinase or purified
      casein kinase I showed similar 32P-peptide patterns.

PMID- 2002044
TI  - Anomalous stimulation of Escherichia coli alkaline phosphatase activity in
      guanidinium chloride. Modulation of the rate-limiting step and negative
      cooperativity.
AB  - Guanidinium chloride stimulates the activity of alkaline phosphatase from
      Escherichia coli, by 3-4-fold. Structural parameters of the enzyme, monitored by
      fluorescence and circular dichroism, indicate progressive denaturation. This
      unusual stimulation is shown to be independent of the nature of the substrate and
      source of the enzyme. Profiles of pH dependence and transphosphorylation reaction
      indicate that the dephosphorylation step of the catalysis is enhanced in the
      presence of guanidinium chloride. We demonstrate, by fast-flow kinetics and
      inhibitor titrations, that guanidinium chloride enhances activity by abolishing
      negative cooperativity and by accelerating the dissociation of rate-limiting
      enzyme and substrate (E.P) complex.

PMID- 2002045
TI  - Structure of the human lipoprotein-associated coagulation inhibitor gene.
      Intro/exon gene organization and localization of the gene to chromosome 2.
AB  - Lipoprotein-associated coagulation inhibitor (LACI) is a multivalent, Kunitz-type
      proteinase inhibitor which appears to play an important role in the regulation of
      hemostasis. LACI directly inhibits factor Xa, and, in a Xa-dependent fashion,
      also inhibits the factor VIIa-tissue factor catalytic complex. Hybridization of a
      LACI cDNA probe to DNA isolated from a panel of human-mouse somatic cell hybrids
      containing different human chromosomes localized the human LACI gene to
      chromosome 2. In situ hybridization to metaphase chromosomes further mapped the
      gene to the region 2q31----2q32.1. Exons of the human LACI gene were cloned from
      genomic or chromosome 2-specific phage libraries and sequenced, including
      approximately 500 base pairs of 5' upstream DNA. The 5' DNA did not contain a
      prototypical TATAA box or CCAAT sequence, and attempts to identify a unique site
      for the initiation of transcription were unsuccessful in that primer extension
      and S1 nuclease protection analysis indicate multiple transcription initiation
      sites for LACI messages. Comparing the gene sequence with LACI cDNA sequences
      indicates that the gene contains nine exons and that alternative splicing can
      occur, resulting in the absence of exon 2 in the 5' untranslated region of some
      messages. The three Kunitz domains in LACI are encoded on separate exons. Introns
      which interrupt coding sequences all occur in the same codon phase interrupting
      the first and second bases of the codon triplets. The data are consistent with
      LACI evolving by a combination of gene segment duplications and exon shuffling.

PMID- 2002046
TI  - Suicide-inhibitory bifunctionally linked substrates (SIBLINKS) as phospholipase
      A2 inhibitors. Mechanistic implications.
AB  - Novel phospholipids that function as mechanism-based inhibitors for phospholipase
      A2 (PLA2) are described. PLA2-catalyzed hydrolysis of the sn-2 ester of these
      suicide-inhibitory bifunctionally linked substrates (SIBLINKS) followed by a
      cyclization reaction generates a cyclic anhydride at the active site of the
      enzyme which leads to inhibition. Structure/activity relationships for the
      SIBLINKS substituents in the sn-1 and sn-2 position are delineated. Time courses
      and efficiency of SIBLINKS inhibition are reported and compared for extracellular
      PLA2s obtained from Naja naja naja, porcine pancreas, bee venom, Crotalus atrox
      and Crotalus adamanteus. SIBLINKS-inhibited PLA2s cannot process either monomeric
      or micellar substrates consistent with inhibition at the catalytic site. Some
      SIBLINKS efficiently inactivate 1 mol of N. naja naja and C. adamanteus PLA2/6-10
      mol of SIBLINKS hydrolyzed. Inhibition of N. naja naja PLA2 can be reversed by
      hydroxylamine, suggesting that a tyrosine residue is acylated.

PMID- 2002047
TI  - Acetaminophen toxicity results in site-specific mitochondrial damage in isolated
      mouse hepatocytes.
AB  - Exposure of isolated mouse hepatocytes to a toxic concentration of acetaminophen
      (5 mM) resulted in damage to the mitochondrial respiratory apparatus. The nature
      of this damage was investigated by measuring respiration stimulated by site
      specific substrates in digitonin-permeabilized hepatocytes after acetaminophen
      exposure. Respiration stimulated by succinate at energy-coupling site 2 was most
      sensitive to inhibition and was decreased by 47% after 1 h. Respiration supported
      by NADH-linked substrates (site 1) was also decreased but to a lesser extent,
      while there was no decrease in the rate of ascorbate + N,N,N',N'-tetramethyl-p
      phenylenediamine (TMPD)-supported respiration (site 3). The loss of mitochondrial
      respiratory function was accompanied by a decrease in ATP levels and ATP/ADP
      ratios in the cytosolic compartment and was preceded by a loss of reduced
      glutathione in both the cytosol and mitochondria. All these effects occurred well
      before the loss of cell membrane integrity. The putative toxic metabolite of
      acetaminophen, N-acetyl-p-benzoquinonimine (NAPQI), produced a similar pattern of
      respiratory dysfunction in isolated hepatic mitochondria. Respiration stimulated
      by succinate- and NADH-linked substrates was very sensitive to 50 microM NAPQI,
      while ascorbate + TMPD-supported respiration was unaffected. The interaction
      between NAPQI and the respiratory chain was further investigated using
      submitochondrial particles. Succinate dehydrogenase (associated with respiratory
      complex II) was found to be very sensitive to NAPQI, while NADH dehydrogenase
      (respiratory complex I) was inhibited to a lesser extent. Our results indicate
      that a loss of the ability to utilize succinate- and NADH-linked substrates due
      to attack of the respiratory chain by NAPQI causes a disruption of energy
      homeostasis in acetaminophen hepatotoxicity.

PMID- 2002048
TI  - A strong mutator effect caused by an amino acid change in the alpha subunit of
      DNA polymerase III of Escherichia coli.
AB  - Most potent mutators heretofore detected in Escherichia coli are associated with
      defects in epsilon subunit of DNA polymerase III, encoded by the dnaQ gene. To
      elucidate the role of the alpha subunit, the catalytic subunit of the polymerase,
      in maintaining the high fidelity of DNA replication, we isolated a mutator
      mutant, the mutation (dnaE173) of which resides on the dnaE gene, encoding the
      alpha subunit. The dnaE173 mutant was unable to grow in salt-free L broth at
      temperatures exceeding 44.5 degrees C and exhibited an increased frequency of
      spontaneous mutations, 1,000 to 10,000-fold the wild type level, at permissive
      temperatures. The mutator effect of dnaE173 mutation is dominant over the wild
      type allele. These phenotypes are caused by a single base substitution, resulting
      in one amino acid change, Glu612 (GAA)----Lys(AAA), in the alpha subunit
      molecule. DNA polymerase III purified from the dnaE173 mutant contained both
      alpha and epsilon subunits, in a normal molar ratio. We found no differences
      between wild type and mutant polymerases in the Vmax, thermolabilities, and salt
      sensitivities. However, the apparent Km for the substrate nucleotide of the
      mutant polymerase was 1/6 of that determined with the wild type polymerase.
      Although the mutant polymerase retained a normal level of 3'----5' exonuclease
      activity, the proofreading capacity determined by "turnover assay" was
      significantly lower in the mutant polymerase, as compared with findings in the
      normal enzyme. It seems likely that the enhanced mutability in the dnaE173 strain
      results from, at least in part, a defect in the editing function of DNA
      polymerase III, and further suggests that a portion of the alpha subunit in which
      the amino acid change resides may be important for the proper setting of the two
      subunits at the replication fork so as to facilitate efficient editing during the
      DNA replication.

PMID- 2002049
TI  - Deacetoxycephalosporin C hydroxylase of Streptomyces clavuligerus. Purification,
      characterization, bifunctionality, and evolutionary implication.
AB  - Deacetoxycephalosporin C hydroxylase from cell-free extracts of Streptomyces
      clavuligerus was stabilized partially and purified to near homogeneity by three
      anion-exchange chromatographies, ammonium sulfate fractionation, and two gel
      filtrations. The hydroxylase was a monomer with a Mr of 35,000-38,000. alpha
      Ketoglutarate, ferrous iron, and molecular oxygen were required for the enzyme
      activity. The hydroxylase was optimally active between pH 7.0 and 7.4 in a 3-(N
      morpholino)propanesulfonic acid buffer and at 29 degrees C. It was stimulated by
      a reducing agent, particularly dithiothreitol or reduced glutathione, and ATP.
      The requirement for ferrous ion was specific, and at least one sulfhydryl group
      was apparently essential for the enzymatic hydroxylation. The Km values of the
      hydroxylase for deacetoxycephalosporin C and alpha-ketoglutarate were 59 and 10
      microM, respectively, and the Ka for ferrous ion was 20 microM. In addition to
      its known hydroxylation of deacetoxycephalosporin C to deacetylcephalosporin C,
      the hydroxylase catalyzed effectively an analogous hydroxylation of 3
      exomethylenecephalosporin C to deacetoxycephalosporin C. Surprisingly, the
      hydroxylase also mediated slightly a novel ring-expansion of penicillin N to
      deacetoxycephalosporin C. The substrate specificity of the hydroxylase is
      overlapping with but distinguishable from that of deacetoxycephalosporin C
      synthase, the enzyme which normally mediates the ring-expansion reaction
      (Dotzlaf, J. E., and Yeh, W. K. (1989) J. Biol. Chem. 264, 10219-10227).
      Furthermore, the hydroxylase exhibited an extensive sequence similarity to the
      synthase. Thus, the two enzymes catalyzing the consecutive reactions for
      cephamycin C biosynthesis in S. clavuligerus represent apparent products from a
      divergent evolution.

PMID- 2002050
TI  - Mechanisms of copper incorporation during the biosynthesis of human
      ceruloplasmin.
AB  - To examine the mechanisms of copper incorporation during ceruloplasmin
      biosynthesis, we developed methods to resolve and identify apo and
      holoceruloplasmin. The identity of holoceruloplasmin was confirmed by oxidase
      activity staining, immunoblotting, 67Cu-ligand exchange, and 67Cu-ligand
      blotting. Following metabolic labeling of human liver and lung cell lines with
      67Cu, newly synthesized holoceruloplasmin was detected in the culture media as
      two species with apparent molecular masses of 84 and 79 kDa. Pulse-chase studies
      demonstrate that exogenous copper is readily available for incorporation into
      newly synthesized ceruloplasmin and that the kinetics of apo and
      holoceruloplasmin synthesis and secretion are identical. Inhibition of N-linked
      glycosylation did not affect the rate or amount of copper incorporated into newly
      synthesized ceruloplasmin but did result in the secretion of a single 68-kDa
      holoceruloplasmin moiety. Despite differences in the kinetics of copper uptake
      between cell lines a linear rate of copper incorporation into newly synthesized
      ceruloplasmin was observed with no evidence of copper exchange following
      biosynthesis. Under the conditions studied, holoceruloplasmin accounted for less
      than 5% of the total ceruloplasmin synthesized and secreted by each cell line.
      The data indicate that copper is incorporated into newly synthesized
      ceruloplasmin early in the course of biosynthesis by a process independent of N
      linked carbohydrate addition. This process of copper incorporation results in an
      apparent conformational change in the ceruloplasmin molecule which does not
      affect the secretory rate of the protein.

PMID- 2002051
TI  - Isoform C beta 2, an unusual form of the bovine catalytic subunit of cAMP
      dependent protein kinase.
AB  - The catalytic (C) subunit is the phosphorylating component of the cAMP-dependent
      protein kinase, a key element in a multitude of hormonally controlled cellular
      functions. The C-subunit, thought to be a solitary protein until several years
      ago, is now known to be a group of isoforms comprising as yet C alpha, C beta,
      and C gamma. We report here the isolation of a full-length cDNA clone coding for
      a hitherto undiscovered isoform of the bovine C-subunit. The end parts of the 5'
      coding region and the 5'-noncoding region of this 3365-base pair clone are
      unique, whereas the rest of the coding region and the 3'-noncoding region are
      identical to those of isoform C beta. The clone has therefore been named C beta
      2. The deduced amino acid sequence of C beta 2 has a length of 397 amino acid
      residues and a calculated molecular mass of 46.1 kDa, thus being some 6 kDa
      higher than that of any known C-subunit. In vitro translation of clone C beta 2
      resulted in a single 46-kDa protein. The unique amino-terminal sequence of C beta
      2 lacks the usual myristoylation site of C-subunits. It contains a stretch of
      hydrophobic residues (residues 7-19) and a stretch which may fold into an
      amphiphilic alpha-helix (residues 16-27) conceivably serving targeting functions.
      The existence of isoform C beta 2 is confirmed by: (i) the isolation of a second
      independent C beta 2 clone, (ii) the development of products of expected size and
      sequence upon amplification from total RNA of various bovine tissues with the
      polymerase chain reaction using C beta 2-specific primers, and (iii) Northern
      blots probed with a cDNA fragment containing exclusively C beta 2 sequence. C
      beta 2 mRNA has a size of 4.4 kilobases and is expressed in various bovine
      tissues, mainly in heart and brain. Both the size and tissue distribution are
      indistinguishable from those of C beta mRNA, thus explaining the failure of
      previous investigations to distinguish it from C beta 2. Southern blotting and
      polymerase chain reaction with genomic DNA indicate that intron sequence(s) exist
      at the C beta 2/C beta deviation site (bases 267/268). The deviation site is
      equivalent to the exon 1/exon 2 splice site of the mouse C-subunit. Since splice
      sites are highly conserved and since not a single mutation is found downstream of
      the deviation site, it is tempting to suppose that C beta 2 and C beta are coded
      by one gene which possesses two alternatively spliced exons 1.

PMID- 2002052
TI  - Saccharomyces cerevisiae transcription factors IIIB and IIIC bend the DNA of a
      tRNA(Gln) gene.
AB  - The ability of Saccharomyces cerevisiae transcription factors IIIC and IIIB to
      bend DNA at their binding sites in a tRNA(Gln) gene has been analyzed by two
      methods that are based on the anomalous electrophoretic mobility of bent DNA in a
      tight gel network. Both transcription factors bend DNA, TFIIIB more than TFIIIC.
      The effective centers of the transcription factor IIIB- and IIIC-induced bends
      are not in helical phase.

PMID- 2002053
TI  - Design of bioactive peptides based on antibody hypervariable region structures.
      Development of conformationally constrained and dimeric peptides with enhanced
      affinity.
AB  - The variable regions of antibody molecules bind antigens with high affinity and
      specificity. This binding is imparted largely by the hypervariable portions of
      the variable region. Hypervariable regions typically fold into reverse turn or
      loop structures. Peptides derived from antibody hypervariable region sequences
      can bind antigens with similar specificity, albeit with markedly lower affinity.
      In this study, cyclic and dimeric peptide analogs of an anti
      idiotypic/antireceptor antibody hypervariable region were developed. This
      antibody (87.92.6) binds to reovirus type 3 receptors on cells as well as to a
      neutralizing anti-reovirus type 3 monoclonal antibody (9B.G5). The cyclic
      peptides were utilized to probe the optimal conformation for binding to both the
      receptor and 9B.G5. By dimerizing or constraining the conformation of these
      peptides, higher affinity binding was produced. By utilizing several different
      cyclic peptides, the optimal conformation for binding was established. The
      conformationally optimized cyclic peptide possessed greater than 40-fold higher
      affinity for the receptor and the idiotype than the linear analog. This study
      suggests that conformationally constrained and dimeric peptides derived from
      antibody hypervariable loop sequences can bind antigens (including receptors)
      with reasonable affinity. hypervariable loop sequences can bind antigens
      (including

PMID- 2002054
TI  - The 2.3-A resolution structure of the maltose- or maltodextrin-binding protein, a
      primary receptor of bacterial active transport and chemotaxis.
AB  - The three-dimensional structure of the maltose- or maltodextrin-binding protein
      (Mr = 40,622) with bound maltose has been obtained by crystallographic analysis
      at 2.8-A resolution. The structure, which has been partially refined at 2.3 A, is
      ellipsoidal with overall dimensions of 30 x 40 x 65 A and divided into two
      distinct globular domains by a deep groove. Although each domain is built from
      two peptide segments from the amino- and carboxyl-terminal halves, both domains
      exhibit similar supersecondary structure, consisting of a central beta-pleated
      sheet flanked on both sides with two or three parallel alpha-helices. The groove,
      which has a depth of 18 A and a base of about 9 x 18 A, contains the maltodextrin
      binding site. We have previously observed the same general features in the well
      refined structures of six other periplasmic receptors with specificities for L
      arabinose, D-galactose/D-glucose, sulfate, phosphate, leucine/isoleucine/valine,
      and leucine. The bound maltose is buried in the groove and almost completely
      inaccessible to the bulk solvent. The groove is heavily populated by polar and
      aromatic groups many of which are involved in extensive hydrogen-bonding and van
      der Waals interactions with the maltose. All the disaccharide hydroxyl groups,
      which form a peripheral polar surface approximately in the plane of the sugar
      rings, are tied in a total of 11 direct hydrogen bonds with six charged side
      chains, one Trp side chain, and one peptide backbone NH, and five indirect
      hydrogen bonds via water molecules. The maltose is wedged between four aromatic
      side chains. The resulting stacking of these aromatic residues on the faces of
      the glucosyl units provides a majority of the van der Waals contacts in the
      complex. The nonreducing glucosyl unit of the maltose is involved in
      approximately twice as many hydrogen bonds and van der Waals contacts as the
      glucosyl unit at the reducing end. The binding protein-maltose complex shows the
      best example of the extensive use of polar and aromatic residues in binding
      oligosaccharides. The tertiary structure of the maltodextrin-binding protein,
      along with the results of genetic studies by a number of investigators, has also
      enabled us for the first time to map the different regions on the surface of the
      protein involved in the interactions with the membrane-bound protein components
      necessary for transport of and chemotaxis toward maltodextrins. These sites
      permit distinction of the "open cleft" (without bound sugar) and closed (with
      bound sugar) conformations of the binding protein by the chemotactic signal
      transducer with which the maltodextrin-binding protein interacts.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 2002055
TI  - Engineered interdomain disulfide in the periplasmic receptor for sulfate
      transport reduces flexibility. Site-directed mutagenesis and ligand-binding
      studies.
AB  - Using recombinant DNA techniques, an Escherichia coli periplasmic sulfate
      receptor or sulfate-binding protein involved in active transport has been
      overexpressed and characterized. This protein is essentially identical in size,
      sequence, antigenicity, and ligand affinity and specificity to the sulfate
      receptor from Salmonella typhimurium whose crystal structure has been refined at
      2 A resolution. The dehydrated sulfate is bound in the deep cleft between the two
      lobes of the bilobate protein. Using the structure of the S. typhimurium as a
      guide, three site-directed mutants (Ser129Cys, Gly46Cys, and Ser129Cys/Gly46Cys)
      have been made. In the Cys129/Cys46 mutant the disulfide has been successfully
      introduced across the opening of the ligand-binding site cleft of the E. coli
      sulfate-binding protein. The dissociation of sulfate from the double mutant
      protein is very slow under oxidizing conditions and increases more than 200-fold
      when reducing agent is added. This effect is attributed to a loss of interdomain
      structural flexibility in the presence of the disulfide, and underscores the
      importance of protein conformational change in binding protein function.

PMID- 2002056
TI  - Multiexon deletion in the procollagen III gene is associated with mild Ehlers
      Danlos syndrome type IV.
AB  - We have characterized a deletion of approximately 9 kilobases which spans from
      intron 33 to exon 48 of one pro-alpha 1 (III) collagen allele in a patient with
      Ehlers-Danlos syndrome type IV. The mutation results in the production of an in
      frame species of mRNA which lacks the sequences corresponding to residues 595
      1,008 of the triple-helical domain. Thus, half of the pro-alpha 1 (III) chains
      synthesized by the patient's fibroblasts are nearly 30% shorter than normal. The
      procollagen III molecules composed of either three normal length or three
      shortened chains are thermally stable and efficiently secreted. In contrast, the
      procollagen III molecules that contain one or two shortened chains are unstable
      and are not secreted. Failure to secrete unstable molecules and a residual
      functional role of the shortened but stable homotrimers may explain the somewhat
      milder phenotype of this individual compared with that of another Ehlers-Danlos
      type IV patient bearing a deletion of similar size in the amino-terminal portion
      of the alpha 1 (III) collagen chain.

PMID- 2002057
TI  - Purification and characterization of ribosomal protein S6 kinase I from Xenopus
      eggs.
AB  - Ribosomal protein S6 kinase I has been purified from unfertilized Xenopus eggs to
      near homogeneity as a Mr = 90,000 protein. S6 kinase I is phosphorylated when
      activated in vivo and can be phosphorylated by mitogen-activated protein kinase
      in vitro. The purified enzyme is inactivated upon treatment with protein
      phosphatase 2A. Immunological data and analysis of substrate specificity
      demonstrate that S6 kinase I is related to, but distinct from, the previously
      characterized S6 kinase II. Both enzymes are members of the ribosomal protein S6
      kinase (rsk) gene family.

PMID- 2002058
TI  - Insulin resistance and diabetes due to different mutations in the tyrosine kinase
      domain of both insulin receptor gene alleles.
AB  - Mutations in the insulin receptor gene can lead to in vivo and in vitro insulin
      resistance and can be the cause of diabetes mellitus in selected patients. We
      have studied a 22-year-old diabetic woman with Type A insulin resistance and
      acanthosis nigricans. Insulin binding to the patient's erythrocytes, monocytes,
      adipocytes, fibroblasts, and transformed lymphocytes was decreased. Receptor
      autophosphorylation and tyrosine kinase activity toward an exogenous substrate
      were reduced in partially purified insulin receptors from the proband's
      transformed lymphocytes. Determination of the nucleotide sequence of the
      patient's insulin receptor cDNA revealed that the subject was a compound
      heterozygote who inherited two different mutant insulin receptor gene alleles.
      The paternal allele contains a missense mutation encoding the substitution of
      glutamine for arginine at position 981 in the tyrosine kinase domain of the
      receptor. The maternal allele contains a nonsense mutation causing premature
      termination after amino acid 988 in the beta-subunit, thereby deleting most of
      the kinase domain. The mRNA encoded by the allele with the premature stop codon
      is likely to be unstable, since mRNA transcripts from this allele were decreased
      markedly compared with the other allele. The mother, who is heterozygous for the
      nonsense mutation, exhibited only mild insulin resistance, whereas the proband
      was severely insulin-resistant; this indicates that the missense mutation is
      biologically significant. In summary, (1) we have identified a patient and her
      family with a genetic form of insulin resistance and diabetes due to a defect at
      the level of the insulin receptor; (2) the proband is a compound heterozygote
      displaying a missense mutation (position 981) in one allele and a nonsense
      mutation (position 988) in the other insulin receptor gene allele; (3) the
      missense mutation is in the kinase domain and encodes a receptor with impaired in
      vitro kinase activity; and (4) based on the in vitro and in vivo phenotype, the
      kinase domain mutation at position 981 is biologically significant leading to
      insulin resistance.

PMID- 2002059
TI  - The Ca2(+)-sensitive cytosolic phospholipase A2 is a 100-kDa protein in human
      monoblast U937 cells.
AB  - Human monoblast U937 cells contain a soluble phospholipase A2 (PLA2) that is
      activated over the range of 150-600 nM Ca2+ and is stable only at neutral pH. We
      have purified this PLA2 over 34,000-fold to near homogeneity using sequential ion
      exchange, hydrophobic interaction, and gel filtration chromatography steps. The
      protein has a Mr of approximately 100,000 (by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis) and an isoelectric point of 5.1. Four lines
      of evidence indicate that this 100-kDa polypeptide represents the PLA2. (i) The
      intensity of staining of the 100-kDa protein was proportional to the degree of
      purification of PLA2 activity, (ii) the relative staining intensity of the 100
      kDa protein precisely paralleled the elution profile of PLA2 activity during
      chromatography steps, (iii) the PLA2 activity recovered from a nondenaturing gel
      (greater than 60% of the total activity applied) coincided exactly with the major
      high molecular weight protein detected by silver staining, and (iv) monoclonal
      antibodies against the 100-kDa protein immunoprecipitated the PLA2. We conclude
      that the cytosolic PLA2 isolated from U937 cells represents a novel, high
      molecular weight PLA2 responding to physiological (intracellular) changes in Ca2+
      concentration and therefore may play a critical role in cellular signal
      transduction processes and the biosynthesis of lipid mediators.

PMID- 2002060
TI  - Reversible inhibition of neutrophil elastase by thiol-modified alpha-1 protease
      inhibitor.
AB  - We have modified the single cysteine residue of alpha 1-protease inhibitor (alpha
      1-PI) with HgCl2, methylmethane thiosulfonate, oxidized glutathione (GSSG), and N
      (1-anilinonaphthyl-4)maleimide (ANM). Whereas native alpha 1-PI combines rapidly
      and quasi-irreversibly with neutrophil elastase, the thiol-modified alpha 1-PI
      derivatives are dissociable reversible competitive inhibitors of the enzyme, with
      values of Ki in the range of 6-7 nM. Removal of the thiol modifications restores
      the rapid irreversible mode of inhibition. Once native alpha 1-PI has combined
      with neutrophil elastase, the enzyme-inhibitor complex retains a reactive thiol
      group, but the two proteins can no longer be dissociated by subsequent reaction
      with ANM, even after exposure to sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. From kinetic measurements of fluorescence, ANM-modified alpha 1
      PI combines with neutrophil elastase via an apparent biomolecular process with a
      second order rate constant on the order of 10(5) M-1 S-1. We estimate a
      dissociation rate constant on the order of 10(-3) S-1. The emission of ANM
      modified alpha 1-PI is increased in intensity and blue shifted from the maximum
      in ANM-modified cysteine, consistent with a predominantly nonpolar environment.
      Association with neutrophil elastase results in an additional blue shift with
      further increase in intensity, consistent with a further decrease in polarity of
      the environment of the cysteine. Modification with methylmethane thiosulfonate or
      GSSG results in a small decrease in quantum yield and a red shift in the
      tryptophan emission spectrum of the modified inhibitor, suggestive of increased
      polarity of the environment of at least 1 of the 2 tryptophan residues in alpha 1
      PI. These changes are reversed by dithiothreitol and are consistent with a
      conformational change which transforms the inhibitory activity from a rapid,
      irreversible mode in native alpha 1-PI to a dissociable competitive mode in the
      mixed disulfide derivatives.

PMID- 2002061
TI  - The DIF-1 signaling system in Dictyostelium. Metabolism of the signal.
AB  - DIF-1 is a novel, chlorinated alkyl phenone from Dictyostelium which, at very low
      concentrations, induces amoebae to differentiate into stalk cells and may act as
      a morphogen in the formation of the prestalkprespore pattern during development.
      We report here the existence of a developmentally regulated metabolic pathway
      which inactivates DIF-1. Radioisotopically labeled DIF-1 was synthesized,
      incubated with developing cells, the metabolites recovered, and then analyzed by
      high pressure liquid chromatography and TLC. At least 12 metabolites are produced
      and the early steps of a complex metabolic pathway have been deduced by following
      the flow of counts from one metabolite to another and by determining the fate of
      purified metabolites when they are incubated with cells. The first metabolite,
      DM1, is largely cell-associated whereas the more distal ones are found mainly in
      the medium. Metabolism inactivates DIF-1, since DM1 retains only 7% of the
      specific activity of DIF-1 in the stalk cell differentiation bioassay and later
      metabolites possess even less activity. Metabolism is developmentally regulated,
      increasing toward the end of aggregation to reach maximal levels at the tipped
      mound stage, as endogenous DIF-1 levels are themselves rising. Cells at this
      stage of development possess the capacity to metabolize their endogenous DIF-1
      with a half-life of a few minutes. We suggest that DIF-1 metabolism is important
      to prevent the DIF-1 receptor system from becoming saturated by excess ligand,
      thus allowing cells to respond to changes in DIF-1 production. Metabolism may
      also produce other effector molecules from DIF-1 or produce DIF-1 gradients in
      the aggregate by the localized destruction of DIF-1.

PMID- 2002062
TI  - Protein kinase C phosphorylates glutamyl-tRNA synthetase in rabbit reticulocytes
      stimulated by tumor promoting phorbol esters.
AB  - A high Mr synthetase core complex isolated from higher eukaryotes contains
      aminoacyl-tRNA synthetases specific for arginine, aspartic acid, glutamic acid,
      glutamine, isoleucine, leucine, lysine, methionine, and proline. Previously, five
      of the synthetases were shown to be phosphorylated in reticulocytes, and the
      glutaminyl- and aspartyl-tRNA synthetases were shown to be selectively
      phosphorylated in response to 8-bromo cAMP (Pendergast, A. M., Venema, R. C., and
      Traugh, J. A. (1987) J. Biol. Chem. 262, 5939-5942). Exposure of reticulocytes to
      phorbol 12-myristate 13-acetate stimulates the selective phosphorylation of one
      synthetase in the complex, glutamyl-tRNA synthetase. Only the glutamyl-tRNA
      synthetase is modified to a significant extent when the purified complex is
      phosphorylated in vitro by protein kinase C; up to 0.7 mol of phosphate is
      incorporated per mol of synthetase. Two-dimensional phosphopeptide mapping shows
      a single tryptic phosphopeptide, which is identical for the enzyme modified in
      vitro by protein kinase C or in phorbol 12-myristate 13-acetate-stimulated cells.
      Phosphorylation in vivo is reproducibly accompanied by a 38 +/- 10% reduction in
      aminoacylation activity of partially purified glutamyl-tRNA synthetase assayed in
      vitro. Phosphorylation in vitro has no detectable effect on aminoacylation. This
      difference may be due to the absence of a required effector molecule which alters
      activity by interaction with the phosphorylated synthetase. Glutamyl-tRNA
      synthetase is one of a growing number of translational components, including
      initiation factors, which are coordinately modified by protein kinase C in
      response to phorbol 12-myristate 13-acetate.

PMID- 2002063
TI  - Structure of the human MDR3 gene and physical mapping of the human MDR locus.
AB  - Two genes, MDR1 and MDR3, constitute the human P-glycoprotein gene family. To
      examine the evolutionary relationship between the three known classes of
      mammalian P-glycoprotein genes, we have cloned the MDR3 gene and compared its
      structure with that of the human MDR1 and the mouse mdr1 (mdr1b) genes analyzed
      by other groups. The MDR3 gene contains 28 exons and 27 of these contain coding
      sequences for the two homologous halves of the protein that correlate with
      functional domains. This structure is virtually identical to that of the human
      MDR1 gene and the mouse mdr1 (mdr1b) gene, indicating that the exon/intron
      structure was fixed before the duplication events that generated different
      classes of P-glycoproteins, but after the P-glycoproteins diverged from related
      genes, like the cystic fibrosis transmembrane conductance regulator (CFTR) gene,
      which has an entirely different exon/intron structure. The four alternatively
      spliced transcripts of the MDR3 gene arise from alternative splicing of exons 23
      and 26. Our analysis of DNA clones covering about 120 kilobases (kb) of the human
      MDR locus, including the entire MDR3 gene (74 kb) and the intergenic region
      between both genes (34 kb), combined with pulsed-field gel electrophoresis data
      shows that the human MDR locus covers about 230 kb. In contrast to the mouse mdr
      genes, both human genes are transcribed in the same direction (MDR3 located
      downstream of MDR1). The CpG-rich sequences marking the 5' ends of both genes are
      hypomethylated to different extents in different cell lines. Hypomethylation
      roughly correlates with transcriptional activity.

PMID- 2002064
TI  - Crystallization of mitochondrial creatine kinase. Growing of large protein
      crystals and electron microscopic investigation of microcrystals consisting of
      octamers.
AB  - Mitochondrial creatine kinase isolated from chicken cardiac muscle was
      crystallized by vapor diffusion techniques. Depending on the growth conditions,
      fine needles and platelets as well as large single crystals appeared after a few
      days. Large crystals were shown to diffract to at least 3.2 A resolution
      (Schnyder, T., Winkler, H., Gross, H., Sargent, D., Eppenberger, H. M., and
      Wallimann, T. (1990) Biophys J. 57, 420 and thus are suited for a detailed X-ray
      analysis in the future. The relatively high density of single crystals measured
      by a linear organic solvent density gradient indicates a tight packing of
      mitochondrial creatine kinase molecules within the crystals. Microcrystals,
      however, were subjected to electron optical examination either after prefixation
      with glutaraldehyde followed by conventional negative staining or by freeze
      fracturing crystals in mother liquor and heavy metal replication with
      platinum/carbon. In both cases the crystals exhibited a square lattice with
      parameters of a = b = 139 A and a = b = 132 A in negatively stained and
      replicated crystals, respectively. No other lattice parameters were found,
      suggesting that these microcrystals represent a quasi-cubic three-dimensional
      lattice, which is in accordance with the finding that the building blocks of the
      crystals are the cube-like octamers described (Schnyder, T., Engel, A., Lustig,
      A., and Wallimann, T. (1988) J. Biol. Chem. 263, 16954-16962). Digital image
      processing applied to electron micrographs of crystals clearly revealed the
      arrangement of mitochondrial creatine kinase octamers in the crystal lattice as
      well as the subdivision of the octamer into its subdomains at a resolution of 23
      A.

PMID- 2002065
TI  - Sequence and inactivation of the pss gene of Escherichia coli.
      Phosphatidylethanolamine may not be essential for cell viability.
AB  - Phosphatidylethanolamine is the only zwitterionic phospholipid in Escherichia
      coli and accounts for 70-80% of the total glycerophospholipids of this organism.
      To investigate the function of phosphatidylethanolamine in E. coli, we
      constructed an inactivated allele (pss93::kan) of the gene encoding the
      phosphatidylserine synthase which catalyzes the committed step to the synthesis
      of phosphatidylethanolamine. Growth of this mutant was dependent on a plasmid
      borne copy of the wild type gene. After curing the mutant of the wild type gene,
      growth stopped when the content of phosphatidylethanolamine reached 30% of the
      total phospholipid. Divalent metal ions at millimolar concentrations suppressed
      the growth phenotype of the mutant in the following order of efficiency: Ca2+
      greater than Mg2+ greater than Sr2+. Although phosphatidylserine synthase
      activity was not detectable, phosphatidylethanolamine was still present at 0.007%
      of the total phospholipid after growth for many generations in rich medium
      containing 20 mM Mg2+. The remainder of the phospholipid was primarily
      phosphatidylglycerol and cardiolipin with no other unique phosphate-containing
      chloroform-soluble material present. The phospholipid to protein ratio and the
      fatty acid composition were very similar to the parental strain. The broad
      divalent metal ion auxotrophy brought about by the lack of
      phosphatidylethanolamine suggests a primarily structural role for this
      phospholipid in E. coli.

PMID- 2002066
TI  - Single proline substitutions in predicted alpha-helices of murine granulocyte
      macrophage colony-stimulating factor result in a loss in bioactivity and altered
      glycosylation.
AB  - Contributions of alpha-helices to biological activity in murine granulocyte
      macrophage colony-stimulating factor were analyzed using site-directed
      mutagenesis and protein expression in COS-1 cells. A series of single proline
      substitutions were made for residues within the four predicted alpha-helices as a
      means of disrupting local helical secondary structure. Mutations in three of the
      four helices resulted in marked reductions in bioactivity. Five mutants E21P,
      L56P, E60P, L63P, and L107P showed 10(2)-10(4)-fold reduction in bioactivity as
      well as hyperglycosylation. The same Pro substitutions made on non-N-glycosylated
      molecules had a similar loss in bioactivity implying that a Pro-induced
      structural change and not hyperglycosylation was responsible for the major
      decrease in bioactivity. Additional amino acid substitutions at these residues
      which conserved charge or hydrophobicity, or replaced the original residue with
      an Ala, verified that conformational changes in the protein structure were
      specifically due to steric constraints imposed by the Pro residue rather than
      loss of important side chain functions.

PMID- 2002067
TI  - DNA sequence recognition by a eukaryotic sequence-specific endonuclease,
      Endo.SceI, from Saccharomyces cerevisiae.
AB  - A eukaryotic sequence-specific endonuclease, Endo.SceI, causes sequence-specific
      double-stranded scission of double-stranded DNA to produce cohesive ends with
      four bases protruding at the 3' termini. Unlike in the case of restriction
      enzymes, an asymmetric 26-base pair consensus sequence was found around the
      cleavage site for Endo.SceI instead of a common sequence. We analyzed the base
      pairs that interacted with Endo.SceI on the recognition of its cleavage sites. A
      region comprising -10 through +16 base pairs from the center of the cleavage site
      was shown to be essential and sufficient for the sequence-specific cutting with
      Endo.SceI by experiments involving synthesized DNAs. Methylation interference
      experiments indicate that bases in the region comprising the +7 through +14 base
      pairs is involved in close contact with Endo.SceI in its recognition of the
      cleavage site. This +7 through +14-base pair region overlaps the most stringently
      conserved sequence in the consensus sequence for the cleavage site, suggesting
      that this region constitutes the core for the recognition by Endo.SceI.

PMID- 2002068
TI  - Human deoxycytidine kinase. Sequence of cDNA clones and analysis of expression in
      cell lines with and without enzyme activity.

PMID- 2002069
TI  - The orthopaedist as traumatologist.

PMID- 2002070
TI  - Interlocking intramedullary nailing for supracondylar and intercondylar fractures
      of the distal part of the femur.
AB  - Thirty-seven fractures of the distal part of the femur in thirty-five patients
      were treated with interlocking intramedullary nailing. All fractures were nailed
      by a closed technique after any intercondylar extension of the fracture had been
      managed by reduction and stabilization with percutaneous lag-screws. Patients who
      had an isolated condylar fracture or a severely comminuted intercondylar fracture
      were treated with other types of implants. There were thirty extra-articular
      (type-A) fractures and seven intra-articular (type-C1 and type-C2) fractures.
      Postoperatively, early mobilization exercises and weight-bearing were begun. At
      an average duration of follow-up of 20.5 months (range, fifteen to twenty-six
      months), all thirty-seven fractures had healed. There were no malunions of either
      the supracondylar or the intercondylar fractures. Complications were infrequent
      and included chronic irritation from the distal screws in three patients and
      delayed union in one; the latter healed with two centimeters of shortening after
      bone-grafting. There were no infections. The functional results were assessed
      with the modified knee-rating system of The Hospital for Special Surgery.
      Thirteen knees (35 per cent) had an excellent result; twenty-two (59 per cent), a
      good result; and two (5 per cent), a fair result. The results correlated with the
      age of the patient and the presence of an intra-articular fracture. We concluded
      that closed interlocking intramedullary nailing is an excellent technique for
      both supracondylar and simple intercondylar fractures in which closed reduction
      and percutaneous fixation of the articular fracture is possible.

PMID- 2002071
TI  - Double-plating of comminuted, unstable fractures of the distal part of the femur.
AB  - The cases of nine patients who had a complex fracture of the distal part of the
      femur and a deficient medial-cortical buttress were reviewed. Stable fixation was
      not achieved with the lateral condylar buttress plate alone. Collapse of the
      distal fragment into varus angulation was noted intraoperatively, with the axis
      of rotation being the junction of the distal screws and the plate. Additional
      stabilization with a medial plate and a bone graft from the iliac crest was
      applied in all nine patients: in six, at the time of the index operation and in
      the remaining three, after the open wound and open fracture were considered
      clean. At an average duration of follow-up of twenty-six months (range, twenty
      one to thirty-four months), all of the fractures had healed. Evaluation of the
      functional outcome revealed five good and four fair results. In three patients,
      less than 90 degrees of flexion of the knee was present and in six, the arc of
      flexion was limited to between 90 and 100 degrees. Additionally, four patients
      had an extensor lag of 5 degrees.

PMID- 2002072
TI  - The joint-contact area of the ankle. The contribution of the posterior malleolus.
AB  - Eight ankles from fresh cadavera were tested under simulated clinical conditions
      to determine the effect of increasing the size of the posterior malleolar
      fracture on the contact area of the ankle joint and on the distribution of joint
      pressure. The surface area of contact decreased with increased size of the
      posterior malleolar fragment. However, the documented changes were smaller than
      expected on the basis of the findings of Ramsey and Hamilton; they reported a 42
      per cent reduction in contact area with only a one-millimeter lateral shift of
      the talus, which clinically would be associated with a similar one-millimeter
      shift of the distal tibial fragment. In addition, clinical experience has shown a
      high rate of post-traumatic degenerative arthritis associated with an
      inadequately reduced one-half-size posterior fragment. There were considerable
      changes in the load-distribution patterns, with increased confluence and
      concentration of loads as the size of the fragment was increased. In plantar
      flexion, many specimens had three separate areas of contact between the tibia and
      the talus. With increased size of the posterior fragment, the three areas of
      contact always joined to become one. Similarly, for all positions of the ankle,
      increased size of the posterior fragment caused decreases in the contact area.
      The maximum loss of contact area was 35 per cent for specimens with one-half-size
      fractures that were tested in the neutral position.

PMID- 2002073
TI  - Treatment of cervical spondylotic myelopathy by enlargement of the spinal canal
      anteriorly, followed by arthrodesis.
AB  - Thirty-seven patients who had enlargement of the spinal canal anteriorly and
      stabilization of the spine for cervical spondylotic myelopathy were followed for
      an average of forty-nine months (range, twenty-eight to seventy months).
      Myelography and computed tomographic myelography were performed preoperatively on
      all patients to determine the location and features of the areas of
      decompression. The canal was enlarged by discectomy; by subtotal corpectomy and
      removal of the anteromedial parts of the pedicles; or by removal of osteophytes
      or of the posterior longitudinal ligament, or both. Partial corpectomy and
      interbody arthrodesis was performed in nine patients; subtotal corpectomy,
      including removal of the posterior parts of the vertebral bodies and of the
      posterior longitudinal ligament, and strut bone-grafting, in fifteen patients;
      and subtotal corpectomy, with detachment of the remaining thin posterior parts of
      the vertebral bodies and of the posterior longitudinal ligament, and strut bone
      grafting, in thirteen patients. Postoperatively, radiographic examinations,
      including myelography and computed tomographic myelography, were performed for
      thirty-six patients and magnetic resonance imaging, for twenty-eight. A
      satisfactory neurological result was obtained in twenty-nine patients. Atrophy of
      the spinal cord, as seen on preoperative computed-tomographic myelograms, was
      predictive of an unsatisfactory result of the decompression, as was weakness of
      the peroneal muscles. All but one of the thirty-seven patients had improved
      walking ability at the most recent follow-up examination: seventeen patients
      improved by 1 point; fourteen, by 2 points; four, by 3 points; and one, by 4
      points. The remaining patient reverted to the preoperative status after an
      initial improvement. The ability to walk at the interim examinations was compared
      with that at the most recent examination; three patients had continuing
      improvement, while three others had deterioration. The main cause of
      deterioration was new spondylotic changes associated with stenosis of the spinal
      canal, occurring at the level of the disc just cephalad to the fused levels. We
      concluded that anterior decompression followed by a secure arthrodesis should be
      an extensive procedure for patients who have cervical spondylotic myelopathy, as
      determined preoperatively from a myelogram or computed tomographic myelogram.
      Excision of the vertebral bodies should also be wide and should include the
      anteromedial parts of the pedicles. The third or fourth cervical vertebra should
      be included in the arthrodesis prophylactically in patients who have stenosis of
      the spinal canal when either of these vertebrae is adjacent to the level of
      fusion.

PMID- 2002074
TI  - Radiographic assessment of instability of the knee due to rupture of the anterior
      cruciate ligament. A quadriceps-contraction technique.
AB  - We compared the results of a radiographic technique for the measurement of
      instability of the knee with those obtained with a KT-1000 arthrometer. The study
      was conducted on both knees of sixty patients who had a ruptured anterior
      cruciate ligament in one knee, as well as in ten control subjects. The
      radiographic technique included the examination of a true lateral radiograph,
      made while the knee was in full extension and the quadriceps was maximally
      contracted, with a 66.7-newton downward force produced by a 6.8-kilogram weight
      suspended from the ankle. As demonstrated by both techniques, the maximum
      difference between the displacements of the right and left knees in the control
      subjects was 2.5 millimeters and the mean difference between the displacements in
      the two knees in the patients was 7.5 millimeters. In fourteen of the sixty knees
      in which the ligament was ruptured, the injury was acute. The forward translation
      of the medial side in these fourteen knees was compared with that in the forty
      six knees in which the injury was chronic. The mean difference in the
      displacement of the medial side in the right and left knees was 3.5 millimeters
      in the fourteen patients who had an acute injury and 5.0 millimeters in the forty
      six patients who had a chronic injury. Thirteen of the sixty patients had
      disruption of the posteromedial corner of the injured knee, and the translation
      of the medial side in these knees was significantly increased compared with that
      in the intact knees of the same patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2002075
TI  - Healing of the transected anterior cruciate ligament in the rabbit.
AB  - Healing of the anterior cruciate ligament was studied in 170 male rabbits. One
      group included immature animals that had open epiphyses, and a second group
      consisted of only mature animals. In one knee of each animal, the anterior
      cruciate ligament was transected either completely or partially, and in the
      contralateral knee a sham operation was carried out. Mechanical testing and
      histological studies of the ligaments were done immediately postoperatively and
      at two weeks, six weeks, three months, and one year. As we expected, there was no
      regeneration after complete transection of the anterior cruciate ligament, and
      all of the animals in which this procedure was done had severe osteoarthrosis of
      the joint at three months. Postoperatively, the partially sectioned ligaments
      exhibited one-third of the strength of the ligaments on the side on which the
      sham operation had been done in the immature animals and one-fourth of the
      strength of the ligaments on the side on which the sham operation had been done
      in the mature animals. Subsequently, there was secondary complete rupture of 20
      per cent of the partially sectioned ligaments. The remaining 80 per cent of the
      partially sectioned ligaments were clearly weaker two weeks after the operation
      than immediately postoperatively, but this was also true on the side on which the
      sham operation had been done. At six weeks, the initial postoperative strength of
      the partially sectioned ligaments had been regained. At one year, the ligaments
      of the immature animals were two-thirds as strong as those on the contralateral
      side, and those of the mature animals were three-fourths as strong as those on
      the contralateral side. The ligaments were markedly elongated, especially in the
      mature animals. At three months, stiffness of the ligaments returned to normal.
      Histologically, the defect was filled with tissue that was still somewhat
      different from normal ligamentous tissue.

PMID- 2002076
TI  - Radial shortening for Kienbock disease.
AB  - The cases of twenty-nine consecutive patients (thirty wrists) who had radial
      shortening for the treatment of stages I through IIIB Kienbock disease were
      reviewed to assess the results of this procedure. Thirteen patients (45 per cent)
      had a history of trauma, and all thirty wrists had a negative ulnar variance
      (average, 2.8 millimeters) on radiographs. All wrists were re-examined after an
      average follow-up of 3.8 years (minimum, two years). At that time, the pain had
      decreased in 87 per cent of the wrists. Extension of the wrist had improved an
      average of 32 per cent; flexion, 27 per cent; radial deviation, 30 per cent;
      ulnar deviation, 41 per cent; and grip strength on the affected side, 49 per
      cent. Analysis of the radiographs by computer digitization showed no significant
      changes in the amount of collapse of the lunate at the latest follow-up. In two
      wrists, there were complications at follow-up (excessive shortening of the radius
      and non-union of the radial osteotomy). Radial shortening is an effective
      treatment for Kienbock disease in wrists that do not have degenerative changes in
      adjacent carpal joints. Pain, range of motion, and strength can be expected to
      improve, but the radiographic appearance of the lunate changes little, if any.

PMID- 2002077
TI  - Chronic posterior subluxation and dislocation of the radial head.
AB  - The clinical and radiographic features of chronic posterior subluxation or
      dislocation of the radial head were studied in thirty-four elbows of twenty-seven
      patients. Three characteristic radiographic types were noted: Type I,
      subluxation; Type II, posterior dislocation with minimum displacement; and Type
      III, posterior dislocation with substantial proximal migration of the radius.
      Follow-up of eighteen patients (twenty-one elbows) revealed that posterior
      displacement did not usually cause serious functional impairment except for loss
      of rotation of the forearm. The least common presentation, Type-I subluxation,
      caused pain and clicking and was associated with late degenerative arthritis.
      Cosmetic deformity due to prominence of the radial head was also a cosmetic
      problem, particularly with Type-III dislocation.

PMID- 2002078
TI  - Survivorship analysis of total knee arthroplasty. Cumulative rates of survival of
      9200 total knee arthroplasties.
AB  - From 1971 through 1987, 9200 total knee arthroplasties were performed at the Mayo
      Clinic. Actuarial analysis was used to estimate cumulative rates of survival. Use
      of a proportional-hazard, general linear model led to the identification of four
      independent variables that were associated with a significantly lower risk of
      failure: primary total knee arthroplasty, a diagnosis of rheumatoid arthritis, an
      age of sixty years or more, and use of a condylar prosthesis with a metal-backed
      tibial component. When all four of these favorable variables were present
      (without regard for radiographic changes and non-disabling symptoms), the
      probability of an implant being in situ was 97 per cent at both five and ten
      years.

PMID- 2002079
TI  - Growth disturbance of the proximal part of the femur after treatment for
      congenital dislocation of the hip.
AB  - The radiographs of ninety patients in whom treatment of unilateral congenital
      dislocation of the hip was complicated by disturbance of growth of the proximal
      part of the femur were studied retrospectively. All patients were followed until
      closure of the affected proximal femoral physis. We divided the patients into
      three groups, according to the degree of vascular insufficiency: patients who had
      mild vascular insufficiency of the hip, which had little effect on growth; those
      who had moderate vascular insufficiency, which produces partial arrest of growth;
      and those who had severe vascular insufficiency, which causes complete arrest of
      growth. Good correlation was found between the initial degree of vascular
      insufficiency and the radiographic results at the most recent follow-up. The
      radiographic signs that were used to predict the extent of physeal involvement
      were a crescent-shaped epiphysis, medial bowing of the femoral neck (a shorter
      and more concave curve between the lesser trochanter and the proximal femoral
      metaphysis [the lateral portion of the Shenton line]), lateral tilting of the
      capital epiphysis, and premature physeal closure. Signs that were diagnostic of
      existing physeal involvement were elevation of the greater trochanter and
      shortening of the affected extremity. The presence and severity of these signs
      correlated well with the degree of vascular insufficiency. Medial bowing was the
      most reliable prognostic factor for the determination of the fate of the hip
      joint at maturity.

PMID- 2002080
TI  - Ipsilateral fractures of the femur and tibia in children and adolescents.
AB  - We reviewed forty-four consecutive cases of simultaneous fracture of the
      ipsilateral femur and tibia in forty-two children and adolescents. One patient
      died from concomitant cerebral injury and one had a fat-embolism syndrome. Thirty
      patients (thirty-two limbs) had an average follow-up of 5.1 years (range, one to
      fourteen years). Nineteen patients who had an average follow-up of 6.8 years were
      available for personal examination and roentgenography. Age was found to be the
      most important variable as related to clinical course. Of the fifteen patients
      who were less than ten years old, three had an early complication; the average
      time to full, unsupported weight-bearing was thirteen weeks; and the average
      combined femoral and tibial overgrowth was 1.8 centimeters. Of the fifteen
      children who were more than ten years old, eight had an early complication; the
      average time to full, unsupported weight-bearing was twenty weeks; and there was
      variable femoral and tibial growth. The juxta-articular pattern of fracture was
      associated with the highest incidence of early and late problems. Most of the
      children who were younger than ten years were treated successfully with closed
      methods, but limb-length discrepancy developed. The children who were older than
      ten years were treated successfully with reduction and fixation of the femoral
      fracture, but had a high rate of complications. There was a high incidence of
      concomitant injuries to the ligaments of the knee, resulting in long-term
      dysfunction of the extremity. Of the nineteen patients who had long-term follow
      up, only seven had normal function without major problems. The remainder had a
      compromised result due to limb-length discrepancy, angular deformity, or
      instability of the knee, particularly ligamentous instability.

PMID- 2002081
TI  - Posterolateral rotatory instability of the elbow.
AB  - Recurrent posterolateral rotatory instability of the elbow is an apparently
      undescribed clinical condition that is difficult to diagnose. We treated five
      patients, ranging in age from five to forty years, who had such a lesion and in
      whom the instability could be demonstrated only by what we call the
      posterolateral rotatory-instability test. This test involves supination of the
      forearm and application of a valgus moment and an axial compression force to the
      elbow while it is flexed from full extension. The elbow is reduced in full
      extension and must be subluxated as it is flexed in order to obtain a positive
      test result (a sudden reduction of the subluxation). Flexion of more than about
      40 degrees produces a sudden palpable and visible reduction of the radiohumeral
      joint. The elbow does not subluxate without provocation. The cause for this
      condition, we think, is laxity of the ulnar part of the lateral collateral
      ligament, which allows a transient rotatory subluxation of the ulnohumeral joint
      and a secondary dislocation of the radiohumeral joint. The annular ligament
      remains intact, so the radio-ulnar joint does not dislocate. Operative repair of
      the lax ulnar part of the lateral collateral ligament eliminated the
      posterolateral rotatory instability, as revealed intraoperatively in our five
      patients.

PMID- 2002082
TI  - Mediastinal widening associated with fractures of the upper thoracic spine.
AB  - Widening of the mediastinum, when seen on radiographs of the chest in victims of
      trauma, is usually attributed to injury to the aorta. An aortic injury, when not
      lethal, often causes paraparesis or paraplegia due to ischemia of the spinal
      cord. A fracture of the upper thoracic spine can produce similar clinical and
      radiographic findings. The cases of three patients who had those findings are
      presented; in all three, the differential diagnosis between the vascular and
      skeletal injuries was difficult. Fracture of the thoracic spine should be
      included in the differential diagnosis whenever mediastinal widening is seen on
      radiographs.

PMID- 2002083
TI  - Magnetic resonance imaging of transient osteoporosis of the hip. A case report.

PMID- 2002084
TI  - Aspergillus osteomyelitis in patients who have chronic granulomatous disease.
      Case report.

PMID- 2002085
TI  - Fractures of the distal end of the radius.

PMID- 2002086
TI  - Displaced intra-articular fractures of the tarsal navicular.

PMID- 2002087
TI  - Aseptic loosening in total hip arthroplasty secondary to osteolysis induced by
      wear debris from titanium-alloy modular femoral heads.

PMID- 2002088
TI  - Use of the Pavlik harness in congenital dislocation of the hip.

PMID- 2002089
TI  - Opioid induction of immunoreactive interleukin-1 in Mytilus edulis and human
      immunocytes: an interleukin-1-like substance in invertebrate neural tissue.
AB  - The synthetic analog of methionine enkephalin, [D-Ala2-Met5]-enkephalin, when
      administered in vitro to Mytilus edulis ganglia and hemocytes and human
      peripheral blood lymphocytes, induces the formation of an immunoreactive
      interleukin-1-like molecule. Additionally, immunoreactive interleukin-1 (IL-1)
      activity has been found in Mytilus nervous tissue. The stimulatory actions of the
      extracted immunoreactive IL-1 on Mytilus hemocytes can be antagonized by an IL-1
      antibody demonstrating the specificity of the substance. The evidence suggests
      that the nervous system, via an opioid-IL-1 relationship, can communicate with
      the immune/defense system through these similar signal molecules. Furthermore,
      the results indicate that an interleukin-like molecule must have evolved earlier
      than previously thought.

PMID- 2002090
TI  - The relationship of interleukin-2 and soluble interleukin-2 receptors to
      intrathecal immunoglobulin synthesis in patients with multiple sclerosis.
AB  - The in vivo relationship of interleukin-2 (IL-2) to the local humoral immune
      response within the central nervous system (CNS) in patients with multiple
      sclerosis (MS) is hitherto largely unknown. Intrathecal levels of IL-2 and
      soluble IL-2 receptors (sIL-2R) were correlated to the local CNS synthesis of
      immunoglobulin G, A, D, and M isotypes in 70 patients with clinically definite
      MS. Levels were also determined in 19 normal control subjects to establish normal
      reference limits. High cerebrospinal fluid levels of IL-2 and sIL-2R were
      detected mainly in patients with acute relapsing-remitting MS and were
      significantly higher than corresponding serum levels. Intrathecal levels of IL-2
      significantly correlated with local CNS synthesis of IgD and IgM, while no
      correlation was found with either IgG or IgA. Similarly, intrathecal sIL-2R
      levels significantly correlated with local CNS production of IgD and IgM, but not
      IgG or IgA. These findings further extend previous reports and also suggest that
      IL-2 and sIL-2R are involved in the early intrathecal humoral immune response in
      MS.

PMID- 2002091
TI  - Oligonucleotide dot-blot analysis of HLA-DQ beta alleles associated with multiple
      sclerosis.
AB  - Oligonucleotide probes were used to investigate the role of DQ beta molecules in
      susceptibility to multiple sclerosis. Although shared amino acid and nucleotide
      sequences in DQ beta 1 have been suggested to be critical in disease development,
      we find that the distribution of sequences corresponding to residues 71-77 is not
      greater in patients versus controls.

PMID- 2002092
TI  - Cytokine levels in the cerebrospinal fluid and serum of patients with multiple
      sclerosis.
AB  - Interleukin (IL) 1 beta, tumor necrosis factor alpha (TNF alpha), and IL-6 are
      cytokines which mediate cellular responses during immune activation and
      inflammation. In multiple sclerosis (MS) they might be responsible for T-cell
      activation (IL-1 beta), for demyelination (TNF alpha), and for immunoglobulin
      (Ig) synthesis (IL-6) within the central nervous system. We studied IL-1 beta,
      TNF alpha, and IL-6 levels in the cerebrospinal fluid (CSF) of 34 patients with
      MS, 43 patients with non-inflammatory neurological diseases (NIND), and 19
      patients with inflammatory neurological diseases (IND). IL-6 was found in the CSF
      of 29% of MS, 7% of NIND, and 47% of IND patients. TNF alpha was detected in the
      CSF of 23% of MS, 7% of NIND, and 29% of IND. CSF IL-6 and TNF alpha levels were
      significantly higher in MS and IND than in NIND. IL-1 beta was rarely detected in
      the CSF of any group. At least one cytokine was detected in 52% of MS CSF, 11% of
      NIND CSF, and 64% of IND CSF. In MS patients, no relationship was observed
      between the incidence or the amount of intrathecal IgG synthesis or oligoclonal
      bands and the presence of any cytokine. We also evaluated cytokine levels in
      paired sera from 11 MS and 13 NIND patients. Low levels of IL-6 were detected in
      most sera from MS and NIND patients. TNF alpha was detected in only two MS sera,
      and IL-1 beta was undetectable in any sample. Our results indicate that increased
      CSF levels of the cytokines IL-6 and TNF alpha occur frequently in MS and IND,
      but there is no obvious relationship to intrathecal Ig synthesis.

PMID- 2002093
TI  - Delayed radiation encephalopathy after radiotherapy for nasopharyngeal cancer: a
      CT study of 45 cases.
AB  - The CT features of 45 cases of delayed radiation encephalopathy (including
      radiation necrosis) following radiotherapy for nasopharyngeal carcinoma are
      reported. The brain lesions were uni- or bilateral and involved mainly the white
      matter and subsequently the gray matter of the lower portion of the brain
      included within the portals of irradiation and its vicinity. The lesions were
      edematous and hypodense on CT and showed postcontrast enhancement in 50% of the
      cases. Within the period of follow-up (1-5 years), the lesions showed remissions
      and exacerbations and in some cases stabilized. In addition, there was
      progressive cerebral atrophy, manifesting itself mainly as dilatation of the
      temporal horns, the neighboring cisterns, and sylvian fissures. In some cases
      that were followed for a long time, the cerebral lesions showed either foci of
      calcification or encephalomalacia and/or porencephaly.

PMID- 2002094
TI  - MR imaging of anisotropically restricted diffusion in the brain of neonates and
      infants.
AB  - Brain MR examinations were performed on one normal and 30 abnormal neonates and
      infants with a variety of clinical problems using pulsed gradient spin echo
      (PGSE) sequences sensitized in different directions to detect changes due to
      anisotropically restricted diffusion of water within the brain. Anisotropically
      restricted diffusion was demonstrated within white matter, which appeared to be
      myelinated with T1-weighted inversion recovery or spin echo sequences and within
      white matter where the presence of myelin was not demonstrated with these
      sequences. Cysts and fluid collections were recognised by their low signal
      intensity using PGSE sequences in the subcortical regions, lentiform nuclei, and
      periventricular regions. An intracerebral hematoma and a subdural hematoma showed
      a high signal intensity with PGSE sequences consistent with isotropically
      restricted diffusion. Chronic infarction displayed a low signal intensity
      consistent with relatively free isotropic diffusion. Patients with leukodystrophy
      associated with congenital muscular dystrophy showed an anisotropic pattern with
      different components of the abnormality present on images with sensitization in
      different directions. The corticospinal tracts failed to show highlighting in
      three cases where conventional imaging was normal. In several patients with a
      history of birth asphyxia, asymmetry and a relative reduction in signal intensity
      were seen in the corticospinal tracts.

PMID- 2002095
TI  - Gadolinium-enhanced MR imaging of cerebral venous angiomas with emphasis on their
      drainage.
AB  - Gadolinium-enhanced MR was performed in 28 patients with 17 supratentorial and 11
      cerebellar venous angiomas. The use of gadolinium allowed detection of 9 of 28
      venous angiomas (32%) that were not visible before gadolinium or which were only
      recognized in retrospect. Before gadolinium the peripheral medullary veins that
      are typical for these venous malformations were only visualized in 4 of 17 (23%)
      supratentorial and in 5 of 11 (45%) cerebellar lesions, for a total of 9 of 28
      (32%) venous angiomas. After intravenous administration of gadolinium these veins
      were seen in 27 of 28 (96%) venous angiomas. Extension of the lesions to the wall
      of the ventricles was seen in 24 of the 28, 16 of 17 supratentorial and 8 of 11
      cerebellar, lesions after gadolinium. This information was missed on plain MR in
      6 of these lesions. The type of venous drainage, either superficial or deep,
      could be determined by gadolinium-enhanced MR in all cases where angiography was
      available for comparison. Before gadolinium this information was not available in
      eight patients. The intravenous administration of gadolinium adds significant
      information in the MR study of venous angioma.

PMID- 2002096
TI  - Pericallosal lipomas: MR features.
AB  - We report on six cases of pericallosal lipomas. The T1-weighted sagittal images
      best demonstrated the relationship between the lipoma and the corpus callosum. In
      four cases the lipomas surrounded the splenium of the corpus callosum and in two
      cases the tumors were situated posteriorly and caudally to the splenium. In no
      case did we encounter an exclusively dorsal pericallosal localization.

PMID- 2002097
TI  - Neurodegenerative diseases of childhood: MR and CT evaluation.
AB  - To evaluate the diagnostic utility of MR and CT in neurodegenerative diseases of
      childhood, we examined 63 children (MR in 44, CT in 53) carrying diagnoses of
      Leigh disease (14 patients), various metabolic diseases (13 patients),
      leukodystrophies (13 patients), other specific degenerative diseases (10
      patients), and unclassified neurodegenerative disorders (13 children). Magnetic
      resonance yielded positive findings in 86% and CT in 81%. Lesion extent and
      conspicuity were consistently greater with MR. The high frequency of
      abnormalities detected on MR, and to a lesser extent on CT, helps distinguish
      children with neurodegenerative diseases from those with nonprogressive
      idiopathic movement disorders. The most common abnormalities included signal
      alterations (MR) or decreased attenuation (CT) of the basal ganglia and cerebral
      white matter, as well as local or generalized brain atrophy. Although
      considerable overlap was present, the findings showed four general patterns that
      may assist in tentative classification of patients with nonspecific clinical and
      laboratory findings.

PMID- 2002098
TI  - MR fat suppression combined with Gd-DTPA enhancement in optic neuritis and
      perineuritis.
AB  - A fat suppression MR technique used in combination with Gd-DTPA enhancement was
      investigated to determine its value in cases of inflammatory optic nerve lesions.
      This technique, the so-called hybrid method, is a derivative of the chopper fat
      suppression technique and provides water-only images without increasing the
      imaging or postprocessing time. The study group consisted of four patients with
      acute visual loss, all of whom received Gd-DTPA. Conventional T2-weighted and fat
      suppression post-Gd-DTPA T1-weighted images were obtained in all patients; in
      addition, in one patient a post-Gd-DTPA T1-weighted image without fat suppression
      was obtained. In three patients, the conventional T2-weighted images failed to
      reveal any abnormality. In contrast, the enhanced optic nerve and enhanced
      perineural inflammatory infiltrate were easily identified on T1-weighted images
      after administration of Gd-DTPA and application of fat suppression technique. The
      lesions in inflammatory optic neuritis or perineuritis were easily distinguished
      from the surrounding fat, which had been suppressed. This combined technique
      resulted in significantly improved definition of normal anatomic structures and
      made the enhancing lesions more conspicuous, especially in areas with large
      amounts of fat such as the retrobulbar orbit.

PMID- 2002099
TI  - MR imaging of spontaneous spinal cord infarction.
AB  - Magnetic resonance imaging was utilized to evaluate three women, one of whom was
      pregnant, with a clinical diagnosis of anterior spinal artery syndrome. In each
      case, development of spinal cord infarctions was spontaneous. Sagittal and axial
      MR images of the spine were obtained prior to and following administration of Gd
      diethylenetriamine pentaacetic acid. Magnetic resonance showed no cord
      enlargement or signal abnormality on T1-weighted images prior to contrast medium
      administration. On T2-weighted images there was abnormal increase in signal
      intensity in the cord at levels corresponding to the neurologic deficits in all
      three patients. Variable contrast enhancement was demonstrated in these areas.
      Magnetic resonance imaging was positive, whereas CT-myelography, carried out in
      the two nonpregnant women, failed to demonstrate any abnormalities.

PMID- 2002100
TI  - The spinal vacuum phenomenon: evaluation by gradient echo MR imaging.
AB  - To evaluate the ability of gradient echo MR to define the vacuum phenomena, 14
      cadaveric lumbar spines were imaged by spin echo and gradient echo MR, CT, and
      plain radiography following injection of varying amounts of air into the
      intervertebral disks. Gradient echo MR was more sensitive than spin echo MR or
      plain radiography in detecting the intradiskal gas collections as small as 0.1
      cc. Computed tomography was a sensitive as gradient echo MR. Plain radiography
      was the least sensitive modality. Increasing the echo time of the gradient echo
      technique increased the conspicuity of the gas collections due to magnetic
      susceptibility effects.

PMID- 2002101
TI  - MR phase-shift velocity mapping of mitral and pulmonary venous flow.
AB  - Mitral and pulmonary venous flows are important indexes in the evaluation of left
      ventricular diastolic function and in the assessment of mitral valve disease. We
      used MR phase-shift velocity mapping to measure mitral and pulmonary venous flow
      velocity in 10 healthy volunteers and mitral flow velocity in 5 patients with
      mitral valve stenosis. Normal mitral flow shows two positive peaks: one during
      early ventricular diastole and the other during atrial contraction. Peak mitral
      flow velocity (mean +/- SD) in early diastole was 68 +/- 12 cm/s and during
      atrial contraction 39 +/- 10 cm/s. The ratio of peak mitral flow velocity in
      early diastole to that during atrial contraction was 1.9 +/- 0.6. In patients
      with mitral valve stenosis, the initial high flow velocity persisted through
      diastole. Peak mitral flow velocity of patients with mitral valve stenosis
      correlated well with values obtained from Doppler echocardiography. Pulmonary
      venous flow showed two positive peaks: one during ventricular systole and the
      other in ventricular diastole. A small backflow during atrial contraction was
      noticed. Peak systolic velocity in the right lower pulmonary vein was 47 +/- 11
      cm/s, peak diastolic velocity was 40 +/- 9 cm/s, and peak backflow velocity was
      14 +/- 3 cm/s. Magnetic resonance velocity mapping is a noninvasive technique for
      the evaluation of time-related flow velocity patterns and for quantitative
      measurement of mitral and pulmonary venous blood flow velocity.

PMID- 2002102
TI  - Detection of aortic arch thrombus using MR imaging.
AB  - Three patients with peripheral embolization and negative echocardiographic
      examinations were studied with MR imaging. Magnetic resonance imaging detected
      aortic arch thrombi in the absence of aortic aneurysm, dissection, or ulcerated
      plaques. By combining spin echo and cine MR sequences, MR enabled us to
      characterize and contrast intravascular mural thrombi reliably without
      application of contrast media. Thus we are assisted in the identification of
      patients at risk for embolization from an often overlooked source: the thoracic
      aorta.

PMID- 2002103
TI  - Semiautomatic evaluation procedures for quantitative CT of the lung.
AB  - Accuracy, reproducibility, and objectivity are important in quantitative
      assessment of lung density and structure by CT, and the measurement has to be
      carried out under tightly controlled conditions. We therefore employ respiratory
      gating at defined levels of inspiration for CT scanning. In the evaluation
      process, we found operator-induced errors of 2-6 HU standard deviation for the
      relatively simple task of global lung density estimates; in regional evaluations,
      they frequently exceeded 10 HU. We therefore developed semi-automated evaluation
      algorithms that isolate lung parenchyma by fast contour tracking and define
      subregions by shrinking, radial segmenting, and anteroposterior subdividing of
      the left and the right lung. Global and regional mean density values and
      histogram parameters were extracted. Based on our clinical studies, we estimate
      that an overall precision of better than 5% can be achieved in quantitative CT of
      the lung with cooperative patients.

PMID- 2002104
TI  - Renal arteriovenous malformations: CT features.
AB  - The CT and clinical features of six patients with congenital renal arteriovenous
      malformation (RAVM) were reviewed to determine the characteristics of this
      condition. The most common symptom was hematuria. The CT images were
      characterized by masses of vascular density located in the renal sinus and
      surrounding the pelvicaliceal system with or without dilated renal veins. The
      exact size of the RAVM and the relation to the pelvicaliceal system were well
      demonstrated by delayed images or drip infusion technique, whereas the bolus
      injection technique was essential to document the vascular nature. The potential
      pitfalls in diagnosis that can occur if only an infusion study is performed are
      discussed.

PMID- 2002105
TI  - Identification of the periprostatic venous plexus by MR imaging.
AB  - T2-weighted images (spin echo 2,000/60) show a high signal intensity rim around
      the prostate. Our investigations show that this rim is not part of the pelvic
      fat; it has T1 and T2 relaxation times similar to heparinized blood; it
      demonstrates little inflow effect; and after an intravenous injection of Gd
      diethylenetriamine pentaacetic acid, its signal intensity increases. We conclude
      that this rim is the periprostatic venous plexus.

PMID- 2002106
TI  - Tuberculosis of the prostate: CT appearance.
AB  - Tuberculosis of genitourinary tract is common in Taiwan. We present two cases of
      tuberculosis of the prostate with their CT findings.

PMID- 2002107
TI  - Imaging of hemodialysis fistulas: limitations of MR angiography.
AB  - The clinical feasibility and utility of a three-dimensional (3D) MR angiography
      (MRA) were evaluated in 20 patients with hemodialysis fistulas. All patients had
      well functioning shunts and were imaged with a fast imaging in steady precision
      (FISP) flow rephased and flow dephased sequence. For comparison digital
      subtraction angiography and color-coded image directed Doppler sonography were
      used. Of 20 patients studied, 4 interrupted the MR examination due to pain in the
      shoulder of the extremity imaged. Of the 16 remaining fistulas only 2 were
      completely displayed on MR including feeding artery, anastomosis, and draining
      vein(s) on the MRA. Although 15 of 16 feeding arteries were shown by MRA, 10 of
      16 draining veins and 14 of 16 anastomoses of the fistulas showed signal voids
      due to a lack of rephasing. Superimposing the MRA on the dephased images helped
      to demonstrate the shunt in another four patients having normal shunts. Thus, the
      utility of 3D MRA in imaging of hemodialysis fistulas is limited by technical
      problems and by patient's cooperation.

PMID- 2002108
TI  - MR and CT appearance of nodular fasciitis.
AB  - Nodular fasciitis is a common soft-tissue tumor that remains almost unreported in
      the radiology literature. We retrospectively reviewed all available imaging
      studies on three patients with nodular fasciitis studied by MR at our
      institution. The lesions were round to oval in configuration, ranging in size
      from 1 to 4.5 cm. Two were intramuscular and one was subcutaneous in location.
      Both intramuscular lesions were poorly defined on CT, with a tissue attenuation
      less than that of skeletal muscle. The single subcutaneous lesion was well
      defined by surrounding fat. Conversely, all lesions were well defined on MR,
      although the appearance was otherwise nonspecific and varied according to the
      histology of the lesion. Both intramuscular lesions were mucoid or cellular and
      were hyperintense to skeletal muscle on T1-weighted and hyper-intense to fat on
      T2-weighted spin-echo (SE) MR images. The subcutaneous lesion was fibrous and
      markedly hypointense to skeletal muscle on all SE pulse sequences. Findings on
      three-phase bone scan, arteriography, and ultrasound are discussed. Because there
      are no unique radiologic findings in nodular fasciitis, this entity must be
      included in the preoperative differential diagnosis of small soft-tissue masses
      occurring in the extremities of young adults.

PMID- 2002109
TI  - Measurement of thyroid iodine by CT.
AB  - For evaluation of thyroidal iodine kinetics and thyroid nodules, we carried out
      quantitative in vivo measurement of thyroid iodine concentration by CT. Neuron
      activation analysis of iodine content was conducted on 48 thyroid fragments
      without calcification operatively obtained from 18 patients who had undergone CT
      of the thyroid without contrast enhancement. The CT attenuation values were
      obtained from the regions of interest in the CT image that corresponded to the
      analyzed fragment. When iodine concentration in the thyroid tissue was greater
      than 0.02 mg/g, the CT values correlated linearly with the iodine concentrations
      in thyroid nodules, thyroids with diffuse thyroid disease, and normal thyroids.
      The relationship is represented by the following formula: iodine concentration
      (mg/g) = (CT value-65)/104. The relationship between iodine concentration and CT
      value in diffuse thyroid disease, thyroid nodules, and normal thyroids was not
      significantly different.

PMID- 2002110
TI  - Validation of a new method for stereotactic localization using MR imaging.
AB  - Magnetic resonance is recognized as potentially the best imaging procedure for
      localization in stereotactic neurosurgery. However, special difficulties
      necessitate specific adaptation to localize targets in the stereotactic frame. We
      developed a new method for stereotactic localization. The MR studies were
      performed using a 0.5 T imager. Four small boxes filled with CuSO4 solution were
      inserted into the intracranial holders of a Talairach frame. Using fast
      sequences, thirty 7-mm thick contiguous sagittal slices and twenty 5-mm thick
      axial slices enabled us to image the entire brain. The image data were
      transferred for analysis to an image processing station, including special
      software to handle stereotactic calculations. The accuracy of the origin of the
      trihedron and systematic geometrical errors were carefully evaluated using a
      cubic phantom, and corrective algorithms were applied when needed. Moreover,
      checks have been designed to detect geometrical distortion due to ferromagnetic
      artifacts, alterations in gradient calibration, or movements made by the patient.
      This localization method does not necessitate the use of stereotactic frames and
      appears to be precise enough for clinical use. Duration of MR examination is not
      a restricting factor, mainly because the patient can be positioned easily.

PMID- 2002111
TI  - Contrast, resolution, and detectability in MR imaging.
AB  - With the introduction of fast scan techniques and high field imagers, the ability
      to achieve very high resolution MR images in reasonable imaging times is now
      possible. Increased resolution allows for better detection of small, high
      contrast pathological features, but at some cost. Increasing resolution leads to
      a nonrecoverable decrease in signal-to-noise ratio per pixel and a loss of low
      contrast detectability for constant imaging time. This article examines the
      tradeoffs between image resolution, signal-to-noise ratio, and low contrast
      detectability in MR imaging. Contrast detail curves are presented for images
      collected in a constant imaging time, with constant field of view and bandwidth
      but at different resolutions, and these are compared with theoretical curves. The
      problem of measuring contrast levels in magnitude images, with different
      resolutions and receiver attenuation values, is discussed and a definition that
      accommodates these parameters developed. In addition, a clinical example is shown
      demonstrating a decrease in soft tissue differentiation with increasing
      resolution, again for fixed imaging time. The results indicate that moving to
      high resolution imaging matrices requires consideration be given to the sacrifice
      in low contrast detectability that occurs. Most importantly, it is shown that
      filtering a high resolution image to a lower resolution image, through nearest
      neighbor averaging, does not regain the detectability lost in initially
      collecting the high resolution image.

PMID- 2002112
TI  - Postpneumocystis aspergilloma in AIDS: CT features.
AB  - We describe a case of aspergilloma complicating a pulmonary cyst secondary to
      Pneumocystis carinii pneumonia in an AIDS patient. The utility of CT in the
      diagnosis is illustrated.

PMID- 2002113
TI  - Intrathoracic extramedullary hematopoiesis secondary to B12 and folate
      deficiency: CT appearance.
AB  - Intrathoracic extramedullary hematopoiesis is an unusual condition, usually
      associated with congenital hemolytic anemias. We present a rare case due to
      vitamin B12 and folate deficiency diagnosed by CT-guided biopsy.

PMID- 2002114
TI  - Proximal interruption of a main pulmonary artery with transpleural collateral
      vessels: CT and MR appearances.
AB  - The plain chest radiographic, CT, and MR findings in a 31-year-old woman with
      proximal interruption of the right main pulmonary artery and transpleural
      collaterals are presented. The diagnosis can be established by both dynamic CT
      and MR. Intercostal collaterals and their transpleural connections are best
      demonstrated with dynamic CT.

PMID- 2002115
TI  - Wegener granulomatosis of the colon: CT and histologic correlation.
AB  - Wegener granulomatosis is a systemic vasculitis with distinct clinical and
      histologic features often characterized with involvement of the upper airway,
      lung, and kidneys. The reported incidence of gastrointestinal involvement is
      relatively rare, with histologic confirmation often lacking. We report a case in
      which gastrointestinal involvement was the principal feature, with CT and
      histologic correlation.

PMID- 2002116
TI  - Hepatic oil embolism following lymphography: CT diagnosis.
AB  - Hepatic oil embolism following lymphography is reported in a 68-year-old man
      admitted for chylous ascites associated with recurrent prostatic carcinoma.
      Abdominal plain radiography, CT, and ultimately liver biopsy strongly support a
      direct lymphatic pathway and are against the role of lymphaticovenous anastomoses
      generally advocated to explain this phenomenon.

PMID- 2002117
TI  - Hepatic metastases: false-negative CT portography in cases of fatty infiltration.

PMID- 2002118
TI  - Primary renal carcinoid: computed tomography, ultrasound, and angiographic
      findings.
AB  - We present a rare case of primary renal carcinoid tumor that metastasized to the
      liver and kidneys. The tumor and the metastases were hypovascular
      angiographically, did not enhance on CT, and were hyperechoic with a hypoechoic
      halo on ultrasound. A similar pattern has been seen in a few cases previously
      reported in the literature.

PMID- 2002119
TI  - Stenosing hemorrhagic ureteritis in a child with Henoch-Schonlein purpura: CT
      appearance.
AB  - Henoch-Schonlein purpura is rarely considered in the differential diagnosis of
      ureteral obstruction in children. Renal ultrasound and intravenous urography may
      reveal hydroureteronephrosis but usually fail to yield a specific diagnosis. In
      this child CT differentiated between an intrinsic ureteral stenosis (hemorrhagic
      ureteritis) and an extrinsic ureteral stenosis (retroperitoneal fibrosis), two
      rare complications of Henoch-Schonlein purpura. The CT findings of hemorrhagic
      ureteritis are described.

PMID- 2002120
TI  - Uterine rupture secondary to trauma: CT findings.
AB  - We describe a case of a ruptured gravid uterus, secondary to motor vehicle
      accident, in a 20-year-old woman. Maternal and fetal injuries associated with
      blunt trauma are described along with the use of CT in pregnant patients.

PMID- 2002121
TI  - CT appearance of panencephalopathic and ataxic type of Creutzfeldt-Jakob disease.
AB  - We present a proven case of Creutzfeldt-Jakob disease with severe involvement of
      white matter and cerebellum. Serial CT showed a unique pattern consisting of
      discrete cerebral and cerebellar atrophy, diffuse white matter hypodensity, and
      progressive enlargement of lateral and fourth ventricles.

PMID- 2002122
TI  - Congenital spondylolisthesis of the 6th cervical vertebra: CT findings.
AB  - The CT demonstration of a case of congenital spondylolisthesis of the C6
      vertebral body is reported. This entity includes bilateral bony defects in the
      pars interarticularis regions, deranged facet joints, as well as a midline bony
      cleft in the spinous process. This congenital deformity should be recognized and
      not mistaken for traumatic spondylolisthesis.

PMID- 2002123
TI  - Bilateral pedicle stress fractures: SPECT and CT features.
AB  - This report discusses the first known reported case of bilateral pedicle stress
      fractures. The importance of early detection and appropriate therapy to promote
      early healing is emphasized. Bone scintigraphy with single photon emission CT is
      favored for initial evaluation with CT recommended to further evaluate areas of
      focal abnormal scintigraphic activity.

PMID- 2002124
TI  - 3D surface rendered MR images of the brain and its vasculature.
AB  - Both time-of-flight and phase contrast magnetic resonance angiography images are
      combined with stationary tissue images to provide data depicting two contrast
      relationships yielding intrinsic discrimination of brain matter and flowing
      blood. A computer analysis is based on nearest neighbor segmentation and the
      connection between anatomical structures to partition the images into different
      tissue categories: from which, high resolution brain parenchymal and vascular
      surfaces are constructed and rendered in juxtaposition, aiding in surgical
      planning.

PMID- 2002125
TI  - Behavioral, cognitive, and pharmacological treatments of panic disorder with
      agoraphobia: critique and synthesis.
AB  - Theoretical, methodologic, and clinical research issues pertaining to these
      treatments are examined as are their strengths, limitations, and possible
      interactions. Attrition, outcome, and maintenance effects are compared. Composite
      indices of clinically significant improvement, endstate functioning, and
      longitudinal adjustment are presented. The article also highlights emerging
      models, theoretical advances, and promising interventions. Advantages and
      limitations of current treatments are discussed, with recommendations for future
      research. It is concluded that significant advances have been made in the
      conceptualization and treatment of panic disorder with agoraphobia.

PMID- 2002126
TI  - Mechanisms of action in cognitive-behavioral and pharmacological interventions
      for obesity and bulimia nervosa.
AB  - In the treatment of obesity, anorexiant medication appears to enhance restraint,
      presumably through altering internal cues, and facilitates weight loss with
      behavioral treatment. However, relapse occurs once medication is withdrawn.
      Antidepressants appear to work similarly, and initial evidence suggests the same
      limitations. Long-term combined pharmacologic and behavioral treatment, however,
      may be useful for some individuals not responding positively to behavioral
      treatment alone. In the treatment of bulimia nervosa, antidepressants appear to
      enhance restraint, whereas cognitive behavioral treatment decreases restraint.
      Thus, these modalities appear to be incompatible, and highly restrictive eating
      is not desirable for those of normal weight. However, for individuals not
      responding to cognitive-behavioral treatment, long-term pharmacologic treatment
      may be an alternative, perhaps combined with a more compatible psychological
      treatment.

PMID- 2002127
TI  - Clinical significance: a statistical approach to defining meaningful change in
      psychotherapy research.
AB  - In 1984, Jacobson, Follette, and Revenstorf defined clinically significant change
      as the extent to which therapy moves someone outside the range of the
      dysfunctional population or within the range of the functional population. In the
      present article, ways of operationalizing this definition are described, and
      examples are used to show how clients can be categorized on the basis of this
      definition. A reliable change index (RC) is also proposed to determine whether
      the magnitude of change for a given client is statistically reliable. The
      inclusion of the RC leads to a twofold criterion for clinically significant
      change.

PMID- 2002128
TI  - Therapies for hyperactive children: comparisons, combinations, and compromises.
AB  - Comparative treatment studies of attention-deficit hyperactivity disorder (ADHD)
      are impeded by methodological quandaries, constricted focus, and the
      heterogeneity of ADHD children, research designs, measures, and treatment
      responsiveness. Comparisons are drawn among three major treatment modalities for
      ADHD: stimulant treatments, primarily methylphenidate; behavioral treatments,
      including contingency management and parent training; and cognitive-behavioral or
      self-regulation therapies. We identify a dozen "...abilities," such as
      communicability, controllability, and constrainability, that compel consideration
      and that convert either-or questions about the single best treatment into more
      comprehensive assessment and intervention strategies. The profusion of problems
      called ADHD mandates multimodal approaches not only to optimize therapeutic
      impact but also to inform theories of developmental psychopathology and
      therapeutic change.

PMID- 2002129
TI  - Long-term effectiveness of behavioral versus insight-oriented marital therapy: a
      4-year follow-up study.
AB  - Four-year follow-up data regarding marital status and marital accord were
      obtained for 59 couples receiving either behavioral (BMT) or insight-oriented
      (IOMT) marital therapy in a controlled outcome study. Although no significant
      group differences had been observed between the 2 treatment conditions at either
      termination or 6-month follow-up, by 4-year follow-up a significantly higher
      percentage of BMT couples had experienced divorce (38% for BMT couples compared
      with 3% for IOMT couples). Results are compared with previous outcome research in
      this area, and recommendations are made for further research.

PMID- 2002130
TI  - Behavioral versus insight-oriented marital therapy: labels can be misleading.
AB  - Snyder, Wills, and Grady-Fletcher (1991) reported a 4-year follow-up comparing
      insight-oriented (IOMT) with behavioral marital therapy (BMT). The effects of
      IOMT were more durable than those of BMT. These comments question the adequacy
      with which the two treatments were represented. The BMT treatment manual
      adequately represents behavioral technology as it existed in 1980 but fails to
      include more recent clinical innovations. The IOMT treatment manual includes many
      clinical skills that are integral to BMT but not included in the BMT manual.
      Documentation is provided that therapists in the BMT condition were not using
      these important techniques. These and other questions regarding the adequacy of
      training and supervision may have compromised the integrity of BMT. Nevertheless,
      the findings do suggest that traditional BMT technology alone may be neither
      necessary nor sufficient for long-term change.

PMID- 2002131
TI  - Individual predictors of outcome in group treatment for incest survivors.
AB  - Sixty-five abused women who participated in time-limited group therapy were
      evaluated before treatment on demographic variables, sexual abuse history,
      characteristics of the family of origin, and initial levels of depression and
      distress. Hierarchical regression analyses were conducted to determine the impact
      of these variables on response to treatment. Results suggest that education,
      marital status, type of sexual contact, and initial levels of depression and
      distress predicted response to treatment. In addition, a history of previous
      therapy showed a tendency to interact with type of group format to predict
      outcome. Implications for therapy and further research are considered.

PMID- 2002132
TI  - A "family-based" approach to the treatment of obese type II diabetic patients.
AB  - Forty-nine obese diabetic patients with obese spouses (diabetic or nondiabetic)
      were randomly assigned to an alone or together condition. Patients in the alone
      group participated by themselves in a 20-week behavioral weight control program;
      their spouses attended assessment sessions only. Patients in the together group
      attended the program with their spouses; both were targeted for weight loss and
      taught social support strategies. Weight losses of patients treated alone and
      together did not differ significantly at posttreatment (19.9 vs. 19.1 lb) or 1
      year follow-up (11.6 vs. 7.0 lb). However, there was a significant interaction of
      treatment and gender; women did better when treated with their spouses, whereas
      men did better when treated alone. A "family-based" approach was not effective
      for these obese Type II diabetic patients as a whole but may be helpful for
      women.

PMID- 2002133
TI  - Predictors of vulnerability to AIDS risk behavior relapse.
AB  - Sixty-eight gay men who earlier attended AIDS prevention sessions were
      longitudinally followed for 16 months and categorized as successful or
      unsuccessful in change maintenance. Psychological and behavioral data obtained
      prior to entry in the prevention program were used as variables to predict long
      term change. Resumption of high-risk sexual practices was associated with younger
      age, earlier history of frequent unprotected receptive anal intercourse with
      multiple partners, greater number of past sex partners, reinforcement value
      levels of high-risk practices and condom use, intoxication preceding sex, lower
      scores on a depression measure, greater belief that HIV infection is largely
      determined by external factors such as chance or luck, and homosexuality
      "outness." Discriminant analysis revealed that 86% of Ss could be classified as
      relapsers or change-maintainers on the basis of these variables. Prevention
      implications are discussed.

PMID- 2002134
TI  - Comparison of behavior therapy and cognitive behavior therapy in the treatment of
      generalized anxiety disorder.
AB  - In a controlled clinical trial, 57 Ss meeting DSM-III-R criteria for generalized
      anxiety disorder, and fulfilling an additional severity criterion, were randomly
      allocated to cognitive behavior therapy (CBT), behavior therapy (BT), or a
      waiting-list control group. Individual treatment lasted 4-12 sessions;
      independent assessments were made before treatment, after treatment, and 6 months
      later, and additional follow-up data were collected after an interval of
      approximately 18 months. Results show a clear advantage for CBT over BT. A
      consistent pattern of change favoring CBT was evident in measures of anxiety,
      depression, and cognition. Ss were lost from the BT group, but there was no
      attrition from the CBT group. Treatment integrity was double-checked in England
      and in Holland, and special efforts were made to reduce error variance. Possible
      explanations for the superiority of CBT are discussed.

PMID- 2002135
TI  - Parent-child interactions in families with alcoholic fathers.
AB  - Adolescent offspring (N = 121) of alcoholic, depressed, and nondistressed fathers
      were observed during problem-solving discussions with their fathers, mothers, and
      with both parents together. Assessments were conducted when parents were and were
      not drinking alcohol. Nondistressed father-child dyads differed from both
      clinical samples in showing higher rates of congeniality and problem solving,
      whereas the impact of alcohol consumption on father-child, mother-child, or
      triadic interactions was not related to diagnostic status of father. Results are
      discussed in terms of the nonspecific effects of parental disturbance on family
      relationships and reasons for the absence of alcoholism specific effects on
      parent-child interaction.

PMID- 2002136
TI  - How "blind" are double-blind studies?
AB  - Psychopharmacological studies usually attempt to eliminate "nonspecific"
      influences on outcome by double-blind designs. In a randomized, double-blind
      comparison of alprazolam, imipramine, and placebo, the great majority of panic
      disorder patients (N = 59) and their physicians were able to rate accurately
      whether active drug or placebo had been given. Moreover, physicians could
      distinguish between the two types of active drugs. Inasmuch as correct rating was
      possible halfway through treatment, concerns about the internal validity of the
      double-blind strategy arise.

PMID- 2002137
TI  - Psychosocial readjustment of Canadian Vietnam veterans.
AB  - A survey study was conducted on the psychosocial readjustment of 164 of the
      estimated 10,000-40,000 Canadians who served in Vietnam with the U.S. military.
      Results indicate significantly greater rates of posttraumatic stress disorder
      (PTSD) compared with U.S. Vietnam veterans. Evidence of other psychosocial
      adjustment problems such as depression, inability to handle frustration and
      anger, difficulty in getting along with and trusting others, and family and
      marital problems, as well as poor physical health, was also found. Results
      suggest these problems are due, in part, to prolonged isolation from other
      Vietnam veterans, lack of recognition, and no readily available treatment for
      PTSD in Canada.

PMID- 2002138
TI  - Husband's aggression toward wives and mothers' and fathers' aggression toward
      children: moderating effects of child gender.
AB  - This study assesses the role of child gender in moderating the association
      between husbands' aggression toward wives and parental aggression toward
      children. Participants were 73 mothers who experienced at least one incident of
      marital aggression during the past 12 months. Each mother had a child between 5
      and 16 years of age. Hierarchical regression analyses indicate that the Husbands'
      Aggression Toward Wives x Child Gender interaction contributed unique variance to
      the prediction of both mothers' and fathers' aggression toward children after
      husbands' aggression toward wives, child gender, and child age were controlled.
      Pearson correlations indicate that husbands' aggression toward wives correlated
      positively with mothers' and fathers' aggression toward boys but not toward
      girls.

PMID- 2002139
TI  - Implications of therapist effects for the design and analysis of comparative
      studies of psychotherapies.
AB  - Technical reasons are presented as to why therapist should be included as a
      random design factor in the nested analysis of (co)variance (AN[C]OVA) design
      commonly used in psychotherapy research. Incorrect specification of the ANOVA
      design can, under some circumstances, result in incorrect estimation of the error
      term, overly liberal F ratios, and an unacceptably high risk of Type I errors.
      Review of studies indicates that the great majority of investigators continue to
      ignore this issue. Computer simulation studies revealed that considerable bias
      can be introduced by not specifying therapist as a random term. Finally, a
      reanalysis is presented of data from 10 psychotherapy outcome studies that
      indicated that therapist effects vary considerably and at times can be large.
      More recent studies that implement better quality controls appear to demonstrate
      less variance due to therapist. The implications of these results for the design
      of future studies are discussed.

PMID- 2002140
TI  - Analysis of change: modeling individual growth.
AB  - Research on change is complicated by problems of measurement and analysis
      stemming from a conceptualization of change as a series of accumulating
      increments and decrements. In contrast, individual growth curves depict change as
      a continuous process underlying individual performance. These two perspectives
      are reviewed, and some problems with the use of difference scores in the study of
      change are clarified. Traditional methods are contrasted with growth curve
      analysis for the purposes of measuring change and studying its correlates. An
      illustrative example of the use of growth curves is provided from research on
      recovery of cognitive function following pediatric closed head injury.

PMID- 2002141
TI  - Using growth modeling to examine systematic differences in growth: an example of
      change in the functioning of families at risk of maladaptive parenting, child
      abuse, or neglect.
AB  - This longitudinal study provides an example of the use of exploratory growth
      modeling to examine changes over time in the functioning of 172 families who
      underwent treatment in an innovative prevention program, Project Good Start. Two
      types of research question are addressed: a within-family question (Does family
      functioning change over time in families at risk of maltreatment who are
      receiving special early support services?) and a between-family question (Are
      changes in family functioning systematically related to selected characteristics
      of family background and treatment?). Results of the study highlight the
      heterogeneity across families in the direction and rate of family function change
      and its systematic relationship with the family profile on entry into
      intervention. Although treatment seems successful in stabilizing and improving
      the family functioning of most at-risk families, problems of
      violence/maltreatment and distressed parenting act to defer successful treatment.

PMID- 2002142
TI  - Modeling transitions in latent stage-sequential processes: a substance use
      prevention example.
AB  - This article illustrates the use of latent transition analysis (LTA), a
      methodology for testing stage-sequential models of individual growth. LTA is an
      outgrowth of latent class theory and is a particular type of latent Markov model
      emphasizing the use of multiple manifest indicators. LTA is used to compare the
      fit of two models of early adolescent substance use onset and to assess the
      effects of a school-based substance use prevention program on Ss measured in 7th
      grade and again in 8th grade. Several interesting findings emerged. First, a
      model of substance use onset including both alcohol and tobacco use as possible
      starting points fit better than a model that included alcohol use as the only
      starting point. Second, Ss who had tried tobacco but not alcohol in in 7th grade
      seemed to be on an accelerated onset trajectory. Third, the normative education
      prevention program was generally successful, except for the students who had
      tried only tobacco in 7th grade.

PMID- 2002143
TI  - Contingency interaction analysis in psychotherapy.
AB  - This article introduces (a) a computerized coding procedure that rates words and
      utterances in terms of emotion, cognition, and contract and (b) a contingency
      method of analyzing verbal interactions. Using transcripts of sessions conducted
      by 3 master therapists with 1 client, the rating procedure and contingency
      correlation analyses supported the study's hypotheses. Therapists' utterances
      were characterized by significantly different amounts of emotion, cognition, and
      contracts, indicating that communication styles varied in the relative emphasis
      placed on these attributes. Differences suggest that the therapists responded
      differently to emotional, cognitive, and contract utterances and that the
      client's responses were different across the 3 therapist interviews. Split halves
      of the interviews within therapists and within client sessions were not
      different, providing further evidence of reliability of the coding and
      contingency procedures.

PMID- 2002144
TI  - Evaluating measurement models in clinical research: covariance structure analysis
      of latent variable models of self-conception.
AB  - Indirect measures of psychological constructs are vital to clinical research. On
      occasion, however, the meaning of indirect measures of psychological constructs
      is obfuscated by statistical procedures that do not account for the complex
      relations between items and latent variables and among latent variables.
      Covariance structure analysis (CSA) is a statistical procedure for testing
      hypotheses about the relations among items that indirectly measure a
      psychological construct and relations among psychological constructs. This
      article introduces clinical researchers to the strengths and limitations of CSA
      as a statistical procedure for conceiving and testing structural hypotheses that
      are not tested adequately with other statistical procedures. The article is
      organized around two empirical examples that illustrate the use of CSA for
      evaluating measurement models with correlated error terms, higher-order factors,
      and measured and latent variables.

PMID- 2002145
TI  - Psychological and pharmacological therapy: methods and modes for comparative
      outcome research.
AB  - Psychological and pharmacological comparative outcome studies are reviewed,
      typically using select examples of cognitive-behavioral interventions from among
      the psychological therapies and of depression from among the disorders. Special
      attention is given to methodological considerations such as selecting outcome
      measures, calibrating the quality of therapy, and investigating client and
      therapist characteristics and the therapeutic relationship. Discussion includes
      consideration of various modes of comparison (i.e., quickness of action, side
      effects, relapse, compliance, cost-effectiveness) that may be used in comparative
      outcome studies. A disorder-specific approach to comparative outcome research is
      seen as a necessary step in the progress toward an increasingly sophisticated
      discrimination of distinctive, complementary, and interactive therapeutic
      processes.

PMID- 2002146
TI  - Introduction to the special section on seeking new clinical research methods.
AB  - This Special Section introduces a new section of the Journal of Consulting and
      Clinical Psychology that will be periodically offered in future issues under the
      title "Clinical Research Methods." This introduction describes (a) the section's
      goals, (b) a conceptual framework and potential areas of methodological
      development, (c) a summary of the articles in the current Special Section and
      their evaluation in terms of the conceptual framework, and (d) editorial policies
      and procedures used to foster innovative development of clinical research
      methods.

PMID- 2002147
TI  - Cognitive therapy and pharmacotherapy for depression.
AB  - Cognitive therapy (CT) for depression has generated considerable interest in
      recent years. Comparisons with tricyclic pharmacotherapy in nonbipolar
      outpatients have suggested that (a) CT may be roughly comparable in the treatment
      of the acute episode: (b) combined CT-pharmacotherapy does not appear to be
      clearly superior to either modality (although indications of potential
      enhancement do exist to justify additional studies with larger samples), and (c)
      treatment with CT during the acute episode (either alone or with medications) may
      reduce the risk of subsequent relapse following termination. Nonetheless, for a
      variety of reasons (e.g., limitations in study design and execution, inadequate
      design power, and possible differential retention), these conclusions can be
      considered only suggestive at this time. More than a decade after the publication
      of the first controlled study involving CT, the approach remains a promising, but
      not adequately tested, alternative to pharmacotherapy in the treatment of
      depression.

PMID- 2002148
TI  - Management considerations for an HIV positive dental student.
AB  - Health care workers who are HIV positive or who have AIDS are faced with unique
      and perplexing problems. Likewise dental students who are HIV positive present a
      special circumstance that demands review of ethical, legal, managerial, and
      medical considerations. The purpose of this paper is to describe the management
      considerations at the Medical College of Georgia following a recent report of an
      HIV positive dental student. The administration assembled a diverse team of
      experts for advice in the situation. This group assumed that the circumstance was
      a potential crisis with possible serious long-term implications. Therefore
      detailed planning, appropriate announcements, and careful management have been
      the administration's principle goal for several weeks. The key management
      strategies and actions are described from the time of notification of the
      student's HIV antibody test results through the initial testing of the patient
      population subgroup.

PMID- 2002149
TI  - Dental hygiene realpolitik affecting education.

PMID- 2002150
TI  - Current status and future trends in dental hygiene education.

PMID- 2002151
TI  - Strategies: Hostos Community College.

PMID- 2002152
TI  - Strategies: the Thomas Jefferson University model.

PMID- 2002153
TI  - Strategies: externship as an enrichment experience.

PMID- 2002154
TI  - Strategies: a conceptual model for Virginia.

PMID- 2002155
TI  - Linking people, professional, and practice.

PMID- 2002156
TI  - The effect of recent trends on dental hygiene.

PMID- 2002157
TI  - Flap dynamics.

PMID- 2002158
TI  - Complications of flaps.
AB  - Flaps are susceptible to the same complications as side-to-side closures.
      However, as the blood supply to a flap is more precarious, the complication may
      have a more dire effect. This article catalogues the various acute complications
      with an emphasis on early recognition and management.

PMID- 2002159
TI  - A regional approach to reconstruction of the upper lip.
AB  - Treatment of upper lip wounds by second intention, full-thickness skin grafts,
      and local flaps is discussed. The location, size, depth, and type of closure for
      each defect in 200 cases involving defects of the upper lip are reviewed. The
      percentages of wounds treated by each modality were 20, 6, 74% for second
      intention, grafts, and local flaps, respectively. Of wound treatment by local
      flaps, 80% used advancement flaps, 10% used transposition flaps, and 10% used
      island-pedicle flaps. Advancement flaps, island-pedicle flaps, possible
      complications, and post-operative care are reviewed.

PMID- 2002160
TI  - Periorbital reconstruction.
AB  - Reconstructions of the lower lid, the upper lid, the medial canthus, the
      infraorbital area, and the eyebrow area are reviewed. Various flap procedures are
      described.

PMID- 2002161
TI  - Local skin flaps on the cheeks.
AB  - Local skin flap repairs on the cheek are discussed. Anatomic and special
      considerations are reviewed. Advancement, rotation, and transposition flaps are
      described.

PMID- 2002162
TI  - Sub-cilial sliding skin-muscle flap repair of anterior lamella lower eyelid
      defects.
AB  - Defects of the anterior lamella of the lower eyelid are common following Mohs
      micrographic surgery. Often, such defects are repaired with free skin grafts. The
      author reviews the treatment of such defects utilizing a single subcilial
      incision to develop a sliding blepharoplasty-type flap, which is advanced
      medially or laterally, as needed, into the defect. Larger defects may require
      Putterman's modified Tenzel flap. Final lid function, position, and cosmesis were
      superior to the results expected from free skin grafts alone in four of the
      author's five cases. Indications, limitations, modifications, technical aspects,
      benefits and potential pitfalls of reconstructive subcilial flaps are discussed.

PMID- 2002163
TI  - Ear reconstruction with local flaps.
AB  - Functional and aesthetic reconstruction of the external ear can be simplified by
      a regional approach utilizing commonly known principles and techniques of
      surgical repair. Reconstructive options are herein offered in a step-by-step
      fashion.

PMID- 2002164
TI  - Reconstruction of the nose with local flaps.
AB  - The author presents the results of a study of 200 patients with surgical defects
      of the nose following excision of skin malignancies. The location, size, depth,
      and quality of the adjacent skin, the reconstruction choice, and the cosmetic
      result were recorded. Healing by second intention was most useful for wounds in
      concave areas. Full-thickness skin grafts were used for defects too large for
      local flaps, or for defects on the nasal tip or alar surface. Local flaps were
      the most useful choice for nasal reconstruction. Transposition flaps, in
      particular, were most useful for each cosmetic sub unit of the nose.

PMID- 2002165
TI  - Scalp flaps.
AB  - The particular anatomy of the scalp largely dictates utilization of its parts and
      adjacent attached integument for reconstructive purposes. Unusually large
      movements of scalp skin are generally required with a variety of basic techniques
      and ancillary procedures. Rotation flaps are considered the prime "work-horses"
      for scalp flap reconstructions. Anatomic factors will be interspersed with
      clinical applications, and a series of photographs and commentary will highlight
      these considerations.

PMID- 2002166
TI  - Forehead reconstruction.
AB  - Guidelines for forehead reconstruction include maintaining or re-establishing
      normal boundaries, preserving nerve function, and maximizing scar camouflage. The
      interrelationships of anatomy, function, and principles of tissue movement which
      are critical to optimal reconstructive planning will be presented.

PMID- 2002167
TI  - A model for the propagation and scattering of ultrasound in tissue.
AB  - An inhomogeneous wave equation is derived describing propagation and scattering
      of ultrasound in an inhomogeneous medium. The scattering term is a function of
      density and propagation velocity perturbations. The integral solution to the wave
      equation is combined with a general description of the field from typical
      transducers used in clinical ultrasound to yield a model for the received pulse
      echo pressure field. Analytic expressions are found in the literature for a
      number of transducers, and any transducer excitation can be incorporated into the
      model. An example is given for a concave, nonapodized transducer in which the
      predicted pressure field is compared to a measured field.

PMID- 2002168
TI  - Wave propagation in a piezoelectric human bone of arbitrary cross section with a
      circular cylindrical cavity.
AB  - A theoretical study of wave propagation in a piezoelectric cylinder of infinite
      length of arbitrary cross section with a circular cylindrical cavity of class 6
      is investigated. The frequency equations are obtained by using the Fourier
      expansion collocation method and are analyzed numerically. The frequencies are
      evaluated for circular, elliptic, and cardioidal sections of bone and are
      tabulated. A plot of frequency spectrum is also presented for the cardioidal
      cross-section bar.

PMID- 2002169
TI  - The influence of systematic primary-tone level variation L2-L1 on the acoustic
      distortion product emission 2f1-f2 in normal human ears.
AB  - The purpose of the present study was to determine the effect of primary-tone
      level variation, L2--L1, on the amplitude of distortion-product otoacoustic
      emissions (DPOAEs). The DPOAE at the frequency 2f1--f2 (f2 greater than f1) was
      measured in 20 ears of ten normally hearing subjects. Acoustic distortion
      products were generated by primaries f1 and f2 with geometric mean frequencies of
      1, 2, and 4 kHz. The f2/f1 ratios were 1.25 (1 kHz), 1.23 (2 kHz), and 1.21 (4
      kHz). The primary-tone level L1 was kept constant at either 65 or 75 dB SPL while
      the second primary-tone level L2 was varied between 20 and 90 dB SPL in 5-dB
      steps. The level differences L2--L1 generating maximal DPOAE amplitudes depended
      on L1 and on the geometric mean frequency of f1 and f2. There were large
      interindividual differences. Overall, the L2--L1 evoking maximal mean DPOAE
      amplitudes was --10 dB for geometric mean frequencies of 1 and 2 kHz with both L1
      = 65 dB SPL and L1 = 75 dB SPL. For 4 kHz, L2-L1 was --5 dB with L1 = 65 dB SPL
      and 0 dB with L1 = 75 dB SPL. The mean slopes of the DPOAE growth functions in
      the initial linearly increasing portions were steeper at higher stimulus
      frequencies, increasing from 0.52 at 1 kHz to 0.72 at 4 kHz for L1 = 65 dB SPL
      and from 0.48 at 1 kHz to 0.72 at 4 kHz for L1 = 75 dB SPL.

PMID- 2002170
TI  - A parametric study of cochlear input impedance.
AB  - In this paper various aspects of the cat cochlear input impedance Zc (omega) are
      implemented using a transmission line model having perilymph viscosity and a
      varying cross-sectional scalae area. These model results are then compared to the
      experimental results of Lynch et al. [J. Acoust. Soc. Am. 72, 108-130 (1982)].
      From the model, the following observations are made about the cochlear input
      impedance: (a) Scalae area variations significantly alter the model Zc (omega);
      (b) the use of anatomically measured area improves the fits to the experimental
      data; (c) improved agreement between model and experimental phase is obtained
      when perilymph viscosity and tapering are included in the cochlear model for
      frequencies below approximately 150 Hz; (d) when model scalae tapering and
      perilymph viscosity are chosen to match physiological conditions, the effect of
      the helicotrema impedance on Zc (omega) is insignificant; and (e) the cochlear
      map, which is defined as the position of the basilar membrane peak displacement
      as a function of stimulus frequency, can have an important effect on Zc (omega)
      for frequencies below 500 Hz. A nonphysiological cochlear map can give rise to
      cochlear standing waves, which result in oscillations in Zc (omega). Scalae
      tapering and perilymph viscosity contribute significantly to the damping of these
      standing waves. These observations should dispel the previous notion that Zc
      (omega) is determined solely by parameters of the cochlea close to the stapes,
      and the notion that Zc (omega) is dominated by the helicotrema at low
      frequencies.

PMID- 2002171
TI  - Frequency resolution as a function of hearing threshold level and age.
AB  - Frequency resolution ability was measured using a psychoacoustical tuning curve
      (PTC) or a notch-noise technique in two population samples. The first sample
      incorporated 1764 subjects with various degrees of sensorineural hearing
      impairment and ranging in age from 17-80 years. The second sample included 240
      subjects aged between 50 and 75 years, carefully balanced in terms of impairment
      and age to avoid confounding between these two variables. In both samples,
      frequency resolution ability declined with increasing hearing threshold level
      (HTL), as measured by either method. In a subsample tested with both methods, the
      correlation between the two was only modest. After accounting for HTL, there was
      a minor dependence of frequency resolution on age, older subjects having poorer
      frequency resolution once HTL had been accounted for. No addition to the
      explained variance was achieved by taking sex, occupational group, or audiogram
      slope into account. Despite the documented reproducibility of the measures, much
      of the variance in the frequency resolution measurements remained unrelated to
      HTL or age.

PMID- 2002172
TI  - Discriminating between coherent and incoherent frequency modulation of complex
      tones.
AB  - A series of experiments measured the discrimination by human listeners of
      frequency-modulated complex tones which differed only in the coherence of
      frequency modulation (FM). For the coherently modulated tones all components were
      modulated by the same 5-Hz sinusoid, and by the same percentage of their starting
      frequencies, whereas for the incoherently modulated tones the modulation of one
      (target) component differed from that of the rest. When the 400-ms complex was
      composed of consecutive harmonics of a common fundamental, performance improved
      monotonically with increases in modulator delay, and was nearly perfect at the
      longest delays. When the complex was inharmonic, performance was near chance at
      all modular delays, both for component frequencies between 1500 and 2500 Hz, and
      for component frequencies between 400 and 800 Hz. It is argued that listeners
      detected incoherence in harmonic complexes by detecting the resulting mistuning
      of the target component. This conclusion was supported by the finding that
      listeners were usually at least as good at detecting a fixed mistuning of the
      center component of a harmonic complex as they were at detecting a modulator
      phase delay imposed on it. A final experiment, with a stimulus duration of 1 s
      and slower modulation rates, showed that listeners could detect incoherence for
      some inharmonic complexes. However, detection was worse than for harmonic
      complexes and was, it is argued, based on weak harmonicity cues. The results of
      all experiments point to the absence of an across-frequency mechanism specific to
      the detection of FM incoherence.

PMID- 2002173
TI  - Segregation of concurrent sounds. II: Effects of spectral envelope tracing,
      frequency modulation coherence, and frequency modulation width.
AB  - The research presented here concerns the simultaneous grouping of the components
      of a vocal sound source. McAdams [J. Acoust. Soc. Am. 86, 2148-2159 (1989)] found
      that when three simultaneous vowels at different pitches were presented with
      subaudio frequency modulation, subjects judged them as being more prominent than
      when no vibrato was present. In a normal voice, when the harmonics of a vowel
      undergo frequency modulation they also undergo an amplitude modulation that
      traces the spectral envelope. Hypothetically, this spectral tracing could be one
      of the criteria used by the ear to group components of each vowel, which may help
      explain the lack of effect of frequency modulation coherence among different
      vowels in the previous study. In this experiment, two types of vowel synthesis
      were used in which the component amplitudes of each vowel either remained
      constant with frequency modulation or traced the spectral envelope. The stimuli
      for the experiment were chords of three different vowels at pitch intervals of
      five semitones (ratio 1.33). All the vowels of a given stimulus were produced by
      the same synthesis method. The subjects' task involved rating the prominence of
      each vowel in the stimulus. It was assumed that subjects would judge this
      prominence to be lower when they were not able to distinguish the vowel from the
      background sound. Also included as stimulus parameters were the different
      permutations of the three vowels at three pitches and a number of modulation
      conditions in which vowels were unmodulated, modulated alone, and modulated
      either coherently with, or independently of, the other vowels. Spectral tracing
      did not result in increased ratings of vowel prominence compared to stimuli where
      no spectral tracing was present. It would therefore seem that it has no effect on
      grouping components of sound sources. Modulated vowels received higher prominence
      ratings than unmodulated vowels. Vowels modulated alone were judged to be more
      prominent than vowels modulated with other vowels. There was, however, no
      significant difference between coherent and independent modulation of the three
      vowels. Differences among modulation conditions were more marked when the
      modulation width was 6% than when it was 3%.

PMID- 2002174
TI  - Detection of tones in reproducible narrow-band noise.
AB  - Hit and false-alarm rates were measured for detection of a 500-Hz tone target in
      each of ten reproducible samples of 1/3-oct bandwidth noise centered at 500 Hz
      for both NoS pi and NoSo conditions. The effects on hit rates of the starting
      phase of the target relative to individual noise samples were investigated with
      two target phase angles for three subjects. The major results are: (1)
      performance varies significantly over masker waveforms; (2) for NoS pi
      conditions, the effect of target-to-marker phase angle on hit rates is not
      significant for these narrow-band maskers; (3) for NoSo conditions, the target-to
      masker phase angle has a large effect; (4) no significant correlation between
      NoSo performance and NoS pi performance is seen across masker waveforms. These
      results are generally consistent wuth previously reported results for wideband
      maskers [R.H. Gilkey, D.E. Robinson, and T.E. Hanna, "Effects of masker waveform
      and signal-to-masker phase relation on diotic and dichotic masking by
      reproducible noise," J. Acoust. Soc. Am. 78, 1207-1219 (1985)] with an important
      exception. Specifically, in the wideband experiment, significant correlation
      between NoSo and NoS pi performance across noise samples was found. In addition,
      in the wideband experiment, a small yet statistically significant effect of
      target-to-masker phase was observed in the NoS pi condition.

PMID- 2002175
TI  - The articulatory kinematics of final lengthening.
AB  - In order to understand better the phonetic control of final lengthening, the
      articulation of phrase-final syllables was compared with that of two other
      contexts known to increase syllable duration: accent and slow tempo. The
      kinematics of jaw movements in [pap] sequences and of lower lip movements in [pe]
      sequences for four subjects were interpreted in terms of a task-dynamic model.
      There was evidence of two different control strategies: decreasing intragestural
      stiffness to slow down some part of the syllable, and changing intergestural
      phasing to decrease overlap of the vowel gesture by the consonant. The first was
      used in slowing down tempo, whereas the second was used to increase the duration
      of accented syllables over unaccented syllables. Both strategies were implicated
      in phrase-final lengthening. In accented syllables, final closing gestures
      generally were longer and slower, but not more displaced. The two slowest
      subjects, however, used the other strategy in their slow-tempo final syllables.
      Final lengthening in reduced syllables was more difficult to interpret. The
      relationship between peak velocity and displacement suggested that a lesser
      stiffness is obscured by an increased gestural amplitude. Thus, by comparison to
      lengthening for accent, final lengthening is like a localized change in speaking
      tempo, although it cannot be equated directly with the specification of
      stiffness.

PMID- 2002176
TI  - Observation of perturbations in a lumped-element model of the vocal folds with
      application to some pathological cases.
AB  - In this paper a mass-spring model is developed that is a hybrid of the two-mass
      and the longitudinal string models, proposed by Ishizaka and Flanagan [Bell Sys.
      Tech. J. 51, 1233-1268 (1972)] and Titze [Phonetica 28, 129-170 (1973)],
      respectively. The model is used to simulate the vibratory motion of both the
      normal and asymmetric vocal folds. Mouth-output pressure, lateral tissue
      displacement, phase plots, and energy diagrams are presented to demonstrate the
      interaction between vocal fold tissue and the aerodynamic flow between the folds.
      The results of the study suggest that this interaction is necessary for sustained
      large amplitude oscillation because the flow supplies the energy lost by the
      tissue damping. Tissue mass and stiffness were varied locally or uniformly.
      Decreased stress in the longitudinal string tension produced subharmonic and
      chaotic vibrations in the displacement, velocity and acceleration phase diagrams.
      Similar vibratory characteristics also appeared in pathological speech data
      analyzed using time domain jitter and shimmer measures and a harmonics-to-noise
      ratio metric. The subharmonics create an effect that has been perceptually
      described as diplophonia.

PMID- 2002177
TI  - Age of learning affects the authenticity of voice-onset time (VOT) in stop
      consonants produced in a second language.
AB  - This study examined whether Spanish-English bilinguals are able to fully
      differentiate Spanish and English /t/ according to voice-onset time (VOT) if they
      learn English as a second language (L2) in early childhood. In experiment 1, VOT
      was measured in Spanish words spoken by Spanish monolinguals, in English words
      spoken by English monolinguals, and in Spanish and English words spoken by
      bilinguals who learned English either as young children or as adults. As
      expected, the Spanish monolinguals produced /t/ with considerably shorter VOT
      values than the English monolinguals. Also as expected, the late L2 learners
      produced English /t/ with "compromise" VOT values that were intermediate to the
      short-lag values observed for Spanish monolinguals and the long-lag values
      observed for English monolinguals. The early learners' VOT values for English
      /t/, on the other hand, did not differ from English monolinguals' VOT. The same
      pattern of results was obtained for stops in utterance-medial position and in
      absolute utterance-initial position. The results of experiment 1 were replicated
      in experiment 2, where bilingual subjects were required to produce Spanish and
      English utterances (sentences, phrases, words) in alteration. The results are
      interpreted to mean that individuals who learn an L2 in early childhood, but not
      those who learn an L2 later in life, are able to establish phonetic categories
      for sounds in the L2 that differ acoustically from corresponding sounds in the
      native language. It is hypothesized that the late L2 learners produced /t/ with
      slightly longer VOT values in English than Spanish by applying different
      realization rules to a single phonetic category.

PMID- 2002178
TI  - VCVs vs CVCs for stop/fricative distinctions by hearing-impaired and normal
      hearing listeners.
AB  - Moderately to profoundly hearing-impaired (n = 30) and normal-hearing (n = 6)
      listeners identified [p, k, t, f, theta, s]  in [symbol; see text], and [symbol;
      see text]s tokens extracted from spoken sentences. The [symbol; see text]s were
      also identified in the sentences. The hearing-impaired group distinguished
      stop/fricative manner more poorly for [symbol; see text] in sentences than when
      extracted. Further, the group's performance for extracted [symbol; see text] was
      poorer than for extracted [symbol; see text] and [symbol; see text]. For the
      normal-hearing group, consonant identification was similar among the syllable and
      sentence contexts.

PMID- 2002179
TI  - Influences of structural factors of biological media on the acoustic nonlinearity
      parameter B/A.
AB  - The influence of structural factors of biological media on the acoustic
      nonlinearity parameter B/A have been studied at the tissue, cellular, and
      molecular levels, using the thermodynamic and finite amplitude methods. B/A was
      determined as the structural factors of the media were altered physically and
      biochemically, while chemical composition was maintained unchanged. Significant
      structural dependencies of B/A were observed at all three levels; 26% of the dry
      weight contribution to the total B/A (the B/A value with water contribution
      subtracted) is due to the cell-cell adhesive force in liver tissue, 20% is due to
      the hepatocyte cellular structure, and 15% is due to secondary and tertiary
      protein structure.

PMID- 2002180
TI  - Polydactyly of the foot in adults: literature review and unusual case
      presentation with diagnostic and treatment recommendations.
AB  - The authors present an unusual case of polydactyly of the foot in an otherwise
      healthy adult male. The modern literature describing polydactyly of the foot is
      reviewed, as well as a review and critique of various classification schemes for
      foot polydactyly deformities. The authors applied the classification criteria of
      Blauth and Olason to an atypical case and to other varied, yet typical,
      presentations of polydactyly of the foot in adults. Nonsurgical and surgical
      treatment options are reviewed, and a rational treatment plan is proposed based
      upon use of the classification scheme. They then apply the management plan for
      symptomatic polydactyly of the foot to the unusual case, and make recommendations
      for surgical management of this deformity.

PMID- 2002181
TI  - Correction of brachymetatarsia with transpositional metatarsal osteotomies.
AB  - The authors present a case history that illustrates their surgical procedure to
      correct congenital hypoplastic metatarsals. The literature is reviewed, and
      surgical alternatives are discussed. Treatment consisted of transpositional
      osteotomies performed between the fourth and fifth metatarsals with good results.

PMID- 2002182
TI  - Acquired flatfoot secondary to tibialis posterior dysfunction: biomechanical
      aspects.
AB  - The biomechanical implications of the normally-functioning tibialis posterior
      muscle and tendon unit, pathomechanics of its dysfunction, and its diagnosis are
      presented. The interaction of the tibialis posterior tendon with the rearfoot
      ligamentous system is discussed. An anatomic consideration of the glenoidal
      ligaments of the talonavicular joint new to the English literature is presented.
      A plan for staging the disease of tibialis posterior dysfunction and classifying
      its etiology is considered to be a prerequisite for proper treatment.

PMID- 2002183
TI  - Metatarsal phalangeal joint arthroscopy.
AB  - An overview of metatarsophalangeal joint (MPJ) arthroscopy is presented.
      Indications, technique, and perioperative management are discussed. The author
      believes it is the operative treatment of choice for various pathology
      encountered in this joint.

PMID- 2002184
TI  - Panmetatarsal head resection and transmetatarsal amputation versus solitary
      partial ray resection in the neuropathic foot.

PMID- 2002185
TI  - Soft tissue calcifications induced by local corticosteroid injection.
AB  - The authors discuss soft tissue calcifications as a possible effect of local
      corticosteroid therapy. The literature will be reviewed and a case report will be
      presented, which illustrates soft tissue calcifications in the heel of a patient
      who received multiple injections of triamcinolone hexacetonide, for heel spur
      syndrome. The accumulation of insoluable steroid acts as a foreign body and
      induced a chronic granulomatous inflammatory process, with subsequent dystrophic
      calcification.

PMID- 2002186
TI  - Use of the Reese osteotomy guide system for fusion of the first
      metatarsophalangeal joint.
AB  - This manuscript presents a new use for the Reese Osteotomy Guide. The technical
      aspect of this procedure is discussed in detail. Advantages and disadvantages of
      its use are reviewed.

PMID- 2002187
TI  - Mitek Anchor System: a new technique for tenodesis and ligamentous repair of the
      foot and ankle.
AB  - The authors present an alternative method for securing tendon and ligaments to
      bone, utilizing the Mitek Anchor System. The description of the Mitek system and
      technique of application is presented. Technical simplicity and ease of
      adaptability within the foot and ankle are distinct advantages of this System.

PMID- 2002188
TI  - Accessory ossicle of the lateral malleolus.
AB  - The authors present a case history of a patient with chronic lateral ankle pain
      and instability secondary to an accessory ossicle of the fibula. Conservative
      therapy failed to alleviate the patient's symptoms, therefore surgical management
      was indicated. The ossicle was excised, and a modified, double-ligament lateral
      ankle stabilization procedure was performed. At 12-months follow-up, the patient
      is symptom-free.

PMID- 2002189
TI  - Corticosteroid-induced avascular necrosis of the talus.
AB  - An unusual case of avascular necrosis of the talus secondary to chronic steroid
      usage is presented, along with a review of the literature. Etiologic factors as
      well as radiographic and clinical features will be discussed. Possible treatment
      alternatives will be reviewed. With greater knowledge of this pathologic process,
      prompt diagnosis may prevent its potentially harmful sequelae.

PMID- 2002190
TI  - Gait analysis in hallux valgus.
AB  - The solar pressure zones were analyzed in the feet of 66 patients suffering from
      hallux valgus, together with 60 normal subjects. The EMED Gait Analysis System
      was used. In the hallux valgus group, the maximum pressure was found to be
      increased significantly in the small toe region and more proximally situated,
      close to the metatarsophalangeal joint. In the normal subjects, the maximum
      pressure was increased significantly in the first, second, third, and fourth
      metatarsal and heel regions. In general, the hallux valgus group had smaller
      contact areas compared to the control group. The increased pressure in the small
      toe region, together with the smaller contact areas manifested by the hallux
      valgus group, were interpreted in this work as being the possible causes of the
      metatarsalgia seen in patients with the deformity.

PMID- 2002191
TI  - Clinical presentation of pedunculated, amelanotic melanoma: plantar aspect.
AB  - An historical review and case history of amelanotic malignant melanoma presenting
      as a pedunculated mass on the plantar aspect of the foot is discussed. The
      patient presented with a rapidly growing, cauliflower-like lesion on the plantar
      aspect of the left foot. Excisional biopsy revealed amelanotic malignancy.
      Subsequent surgical intervention was performed to effect a radical excision of
      local tissues with grafting and inguinal lymphadenectomy.

PMID- 2002192
TI  - Ankle fusion: techniques and complications.
AB  - Ankle fusion is an extremely useful operation. It has the capacity to allow a
      crippled patient to re-enter the mainstream of life from an otherwise disabling
      injury or joint disease situation. It requires careful attention to details and
      the principles of alignment and execution of the procedure in an exacting
      fashion. Improper position can strain adjacent joints, causing pain and
      degeneration with the need for additional fusion surgery. Some shortening of
      approximately 1 to 2 cm usually will result. The surgeon should understand all of
      the special modifications of the fusion procedure so he can tailor the specific
      modification for his circumstance. When done properly in the appropriate
      situation, ankle fusion is an impressive operation for salvage of otherwise
      hopeless situations.

PMID- 2002193
TI  - Diagnostic imaging approach to stress fractures of the foot.
AB  - The authors discuss the radiologic appearance of stress fractures in the foot.
      Plain radiographs, computerized tomograms, bone scintigraphy, and magnetic
      resonance imaging are illustrated. Common areas of pedal fracture including the
      metatarsal bones and, less frequently, the navicular, calcaneus, and other
      rearfoot entities are reviewed. A keen sense of suspicion by the practitioner is
      necessary in identifying these anomalies.

PMID- 2002194
TI  - Neurilemmoma of the foot.
AB  - This case reviews a neurilemmoma discovered beneath the second metatarsal in an
      adult male. Its anatomic appearance is illustrated with the assistance of
      magnetic resonance imaging. Histologic sections are also analyzed, and
      characteristic cellular patterns depicted.

PMID- 2002195
TI  - Age-related changes in the relative growth of the posterior fossa.
AB  - We have established a normative data set for the relative size of the structures
      of the midline posterior fossa from birth to 90 years old. Data were obtained
      from morphometric analysis of midsagittal magnetic resonance imaging scans of the
      brain utilizing a simple image analysis system. There are several significant
      changes in the size of these structures with an increase in chronologic age. The
      relative size of the cisterna magna decreases with age. Anterior cerebellar
      vermal lobules (I through V) appear to grow more rapidly than the rest of the
      cerebellum. Other, less significant, trends include a decrease in the overall
      size of the cerebellum, superior posterior vermal lobules (VI and VII) and
      inferior posterior lobule (VIII) with an increase in age. It is, therefore,
      necessary to use age-standardized normative data when making morphometric
      correlations with clinical disorders.

PMID- 2002196
TI  - An extended phenotype of an early-onset inherited nonprogressive cerebellar
      ataxia syndrome.
AB  - A father and son with presumed dominantly inherited, nonprogressive, early-onset
      cerebellar ataxia are reported. The clinical features are similar to those in
      other reports of this rare disorder, but magnetic resonance imaging revealed
      generalized atrophy of the cerebellum and not localized vermal atrophy as
      previously noted. This family illustrates either an extended phenotype of the
      previously reported disorder or possibly an unique type of autosomal dominant
      cerebellar ataxia.

PMID- 2002197
TI  - Modified encephaloduroarteriosynangiosis as a surgical treatment of childhood
      moyamoya disease: report of five cases.
AB  - Moyamoya disease is an idiopathic disorder characterized by progressive occlusion
      of the internal carotid and anterior and middle cerebral arteries, with formation
      of an extensive abnormal collateral circulation at the base of the brain. Many
      neurosurgical procedures have been designed to bypass these occluded vessels. The
      results of one of these procedures, modified encephaloduroarteriosynangiosis was
      reviewed in five children followed for 3 1/2 to 19 1/2 years. Modified
      encephaloduroarteriosynangiosis performed unilaterally in one and bilaterally in
      four of the children, appeared to halt neurologic deterioration, despite
      angiographic progression, in four of the five children.

PMID- 2002198
TI  - Valproate toxicity: risk-screening strategies.

PMID- 2002199
TI  - Labor and delivery characteristics and the risk of germinal matrix hemorrhage in
      low birth weight infants.
AB  - To assess the influence of labor and delivery events on the risk of germinal
      matrix hemorrhage in preterm newborns, we conducted a review of data collected on
      449 babies who weighed 1.5 kg or less. Babies delivered vaginally were more
      likely to have germinal matrix hemorrhage than were babies delivered abdominally
      (odds ratio, 2.5; 95% confidence interval, 1.4,3.3). Among babies delivered
      vaginally, the risk of germinal matrix hemorrhage was increased by 39% if labor
      lasted more than 12 hours. Among babies delivered abdominally, the occurrence of
      any labor was accompanied by a 150% increased risk of germinal matrix hemorrhage.
      The only indication for abdominal delivery associated with an increased risk of
      germinal matrix hemorrhage was impending amnionitis (odds ratio, 2.6; 95%
      confidence interval, 1.2,5.7), whereas the only indication associated with a
      decreased risk was preeclampsia (odds ratio, 0.2; 95% confidence interval, 0.6).
      Epidural and local anesthesia were associated with a reduced risk of germinal
      matrix hemorrhage among babies delivered abdominally. We conclude that delivery
      practices, or their indications, appear to influence the risk of germinal matrix
      hemorrhage in low birth weight babies.

PMID- 2002200
TI  - Neuropathologic findings in Reye syndrome.
AB  - Brain tissue from three patients with a clinical diagnosis of Reye syndrome was
      compared with tissue from three control patients. All Reye syndrome patients
      demonstrated cytotoxic cerebral edema, with swelling of astrocyte foot processes,
      which was not seen in controls. Myelin sheath splitting was seen both in controls
      and patients, but myelin blebs were uncommon in both. Mitochondrial changes also
      were not seen. Although cerebral edema is a nonspecific finding, it appears to be
      characteristic of Reye syndrome.

PMID- 2002201
TI  - Steroid-dependent postvaricella encephalomyelitis.
AB  - Postinfectious encephalomyelitis is an acute demyelinating illness that usually
      has its onset 3 to 7 days after the onset of a viral exanthem and has a
      monophasic course over 2 to 4 weeks. Recurrent bouts of postinfectious
      encephalomyelitis have been described that have resolved spontaneously or with
      short courses of steroid therapy. We report a patient who developed a chronic,
      steroid-dependent encephalomyelitis secondary to a varicella infection at 5
      months of age.

PMID- 2002202
TI  - Fever producing ballismus in patients with choreoathetosis.
AB  - We report two children with choreoathetoid cerebral palsy who had intermittent,
      severe, paroxysmal episodes of ballismus in response to febrile illnesses. These
      episodes lasted for hours and were difficult to control, requiring large doses of
      haloperidol or phenytoin. Differentiation from seizures triggered by fever was
      readily made by concurrent electroencephalographic recordings.

PMID- 2002203
TI  - Large postnatally acquired porencephalic cysts: unexpected developmental
      outcomes.
AB  - To determine the neurodevelopmental outcome for infants with posthemorrhagic
      intraparenchymal cysts, we reviewed retrospectively clinical, ultrasonographic,
      and developmental features in 16 affected children. At a mean follow-up age of 33
      months, five subjects had normal cognitive outcomes (developmental quotient [DQ]
      or IQ greater than 83), nine had borderline to mild deficits (DQ or IQ, 52 to
      83), but only three had moderate to severe deficits (DQ or IQ less than 52).
      Spastic cerebral palsy was present in 13 (81%); only one child (6%) had a chronic
      seizure disorder requiring medication. Cognitively normal children were less
      likely to have had neonatal seizures (P less than .05) and tended to have more
      localized cysts. Otherwise, we found no relationship between outcome and neonatal
      clinical or laboratory findings. Overall, these results suggest that although
      motor deficits are common in infants with severe intraventricular hemorrhage and
      porencephalic cysts, cognitive outcomes may be more favorable than has been
      suspected previously.

PMID- 2002204
TI  - Academic underachievement in children with epilepsy.
AB  - Academic achievement was studied in 78 children with epilepsy, ages 5 to 13
      years, to determine how seizures, treatment of seizures, and sociocultural
      factors influence academic achievement. Cognitive abilities were assessed with
      either the McCarthy Scales of Children's Abilities or the Wechsler Intelligence
      Scale for Children--Revised. Achievement was measured with the Peabody Individual
      Achievement Tests. Achievement scores were corrected for cognitive ability (IQ),
      and underachievement was defined as achievement score 1/2 standard deviation or
      more below IQ. Information regarding seizure history (severity, duration) and
      treatment with anticonvulsant drugs was obtained. In addition, the family was
      extensively interviewed regarding the child's environment, behavior, and
      demographic background. The Home Observation for Measurement of the Environment
      (HOME) scale was completed on a home visit. Underachievement was frequent,
      ranging from 16% (Reading Recognition) to 50% (General Knowledge), but there was
      no relationship between severity or duration of seizure disorder or total
      exposure to anticonvulsant medications and achievement. Major determinants of
      achievement included subscales of the HOME scale, age (older children more likely
      to be underachieving), and parental education. An equal proportion of newly
      diagnosed and/or untreated subjects were underachieving compared to those with
      longstanding epilepsy and anticonvulsant drug treatment.

PMID- 2002205
TI  - Carnitine, valproate, and toxicity.
AB  - Carnitine is an important nutrient that is present in the diet (particularly in
      meat and dairy products) and is synthesized from dietary amino acids. It
      functions to assist long-chain fatty acid metabolism and to regulate the ratio of
      free coenzyme A to acylcoenzyme A in the mitochondrion. Carnitine deficiency
      occurs in primary inborn errors of metabolism, in nutritional deficiency, and in
      various other disorders including antiepileptic drug therapy. Valproate therapy
      is often associated with decreased carnitine levels and occasionally with true
      carnitine deficiency. Some experimental and clinical evidence links valproate
      induced carnitine deficiency with hepatotoxicity, but this evidence is limited
      and inconclusive. Carnitine supplementation has been useful in some studies, but
      these data are also limited. Young children with neurologic disabilities taking
      multiple antiepileptic drugs may have the greatest risk for carnitine deficiency.
      Measurement of carnitine levels appears warranted in these patients and in
      patients with symptoms and signs of possible carnitine deficiency.

PMID- 2002206
TI  - Sleep-disordered breathing in Mobius syndrome.
AB  - Mobius syndrome is a complex neurologic disorder characterized by congenital
      bilateral facial paralysis associated with lateral gaze paralysis. The syndrome
      has variable manifestations and several variants, some with somatic stigmata. In
      1990, Mobius syndrome is conceptualized as a spectrum of clinical caudal brain
      stem signs. Some deficits are manifested by laryngeal paralysis and aspiration.
      Sleep-disordered breathing syndromes have not been previously reported in
      association with Mobius syndrome. We report two children with Mobius syndrome and
      sleep-disordered breathing. Based on known pathologic findings and clinical
      manifestations, we believe that sleep-disordered breathing may be a common
      complication of Mobius syndrome and should be sought, since potential outcomes of
      such complications include serious morbidity.

PMID- 2002207
TI  - The future of child neurology.

PMID- 2002208
TI  - Hereditary cerebellar hypoplasia.

PMID- 2002209
TI  - Attention deficit hyperactivity disorder (ADHD).

PMID- 2002210
TI  - Activating tasks for the study of visual-spatial attention in ADHD children: a
      cognitive anatomic approach.
AB  - The clinical label attention deficit hyperactivity disorder (ADHD) suggests that
      this syndrome is a disorder of attention. However, the presumed attentional
      deficits have not been linked either to specific cognitive operations or to
      specific neural systems. To provide this link, theories of the cognitive anatomy
      of attention were used to generate hypotheses about specific visual-spatial
      attentional deficits in children with ADHD. A cued reaction-time test was used to
      assess covert and overt shifts of attention theoretically linked to two
      neuroanatomically defined attentional systems in the posterior and anterior parts
      of the human brain. The early, posterior-based covert shift of attention was
      found to be normal in ADHD children, but a later, anterior-based overt shift of
      attention was abnormal as reflected by a significant lateral difference in
      reaction time. This was interpreted as a failure to sustain focused attention.

PMID- 2002211
TI  - The go-no go test in attention deficit disorder is sensitive to methylphenidate.
AB  - The go-no go test requires a subject to emit a simple motor response to one cue
      while inhibiting the response in the presence of another cue. This test has been
      effective in demonstrating impulsivity (elevated commission error rate) in
      children with attention deficit disorder (ADD). In this study, we examined the
      effects on go-no go test performance of two doses of methylphenidate (0.15 mg/kg
      and 0.3 mg/kg) administered in double-blind placebo-controlled fashion to
      children with ADD. Our results indicate that even modest doses of methylphenidate
      improve the go-no go performance of these children by decreasing their tendency
      to make impulsive commission errors. Thus the test is sensitive to the effects of
      methylphenidate and can be used to monitor a response to therapy.

PMID- 2002212
TI  - Comorbidity: a critical issue in attention deficit disorder.
AB  - In this report, we examine the interrelationships between attention deficit
      disorder (ADD), learning disabilities (LD), and conduct and oppositional
      disorders (COD). We indicate that it is reasonable to consider ADD as a distinct
      entity, frequently co-occurring with LD on the one hand, and COD on the other.
      The first section reviews the interrelationships between ADD and LD. Here we
      focus on definitional issues, trace the historical antecedents of ADD and LD,
      examine the prevalence of ADD and LD, and review studies designed to
      differentiate cognitive from attentional mechanisms in children with ADD, LD, or
      both. In the next section, we review the evidence linking ADD with COD, a
      distinction blurred in earlier investigations by problems with referral bias.
      More recent studies suggest that the antecedents, clinical characteristics, and
      prognosis may differ in children with ADD alone compared to those with ADD in
      association with COD.

PMID- 2002213
TI  - Toward a neurobiologic nosology of attention deficit hyperactivity disorder.

PMID- 2002214
TI  - Attention deficit hyperactivity disorder: the differential diagnosis.
AB  - Children and adolescents doing poorly in school or at home or both are often
      labelled as suffering from attention deficit hyperactivity disorder (ADHD).
      Frequently the referred child is not examined systematically for the presence of
      other disorders. This paper presents the diagnostic criteria and management of
      disorders that may be wrongly identified as ADHD or may coexist with ADHD, thus
      complicating identification and treatment. The disorders discussed are
      depression, mania, primary disorder of vigilance, narcolepsy, developmental
      specific learning disorders, conduct disorders, and acquired neurologic deficits.

PMID- 2002215
TI  - Attention deficit disorder without hyperactivity: a distinct behavioral and
      neurocognitive syndrome.
AB  - This study examined the issue as to whether or not children carefully diagnosed
      as having either attention deficit disorder with hyperactivity (ADDH) or without
      hyperactivity (ADDnoH) could be distinguished on selected cognitive, academic,
      rapid naming, and behavioral measures. Employing a previously validated
      multimodal, multi-informant diagnostic process that results in reliable clinical
      diagnoses, 10 ADDH and 10 ADDnoH children were examined. While no significant
      differences in cognitive ability were noted between groups, significant
      underachievement was found in the children diagnosed as ADDnoH, particularly in
      mathematics achievement. The ADDnoH children were also significantly slower on
      rapid naming tasks than the ADDH children. Further, 60% of the ADDnoH children
      had a codiagnosis of a developmental reading or arithmetic disorder while none of
      the ADDH children received such a codiagnosis. Conversely, 40% of the ADDH
      children had a codiagnosis of conduct disorder and were rated by their parent as
      significantly more motorically active, impulsive, and deviant in the
      demonstration of age-appropriate social skills. These findings are discussed as
      they relate to the notion that children with attention deficit disorder may
      suffer from a right hemispheric syndrome.

PMID- 2002216
TI  - Attention deficit hyperactivity disorder-residual type.
AB  - Evidence for the persistence into adult life of attention deficit hyperactivity
      disorder (ADHD) has accumulated in publications of the past two decades. As
      reviewed here, retrospective and longitudinal data suggest that a residual type
      of ADHD (ADHD-RT) can be recognized. Diagnostic historical interview and
      checklist criteria, primarily the Utah set developed by Wender and colleagues,
      have been proposed. The difficulties of obtaining reliable and valid historical
      information, which are greater than those encountered in diagnosing childhood
      cases, add to the desirability of some direct examination for ADHD-RT. It is
      proposed herein that assessment of the neuropsychological domain of executive
      function--broader than, yet encompassing, several facets of attention--offers
      opportunities for documentation of the cognitive correlates of ADHD-RT, its
      responsiveness to therapeutic intervention, and clues as to its neurobiological
      foundation.

PMID- 2002217
TI  - Legal issues in the treatment of children with attention deficit hyperactivity
      disorder.
AB  - The treatment of children with attention deficit hyperactivity disorder (ADHD)
      has raised a number of legal issues. Tort issues include medical malpractice and
      battery claims. Suits have charged physicians with negligent misdiagnosis of
      ADHD, and failure to obtain adequate informed consent for the use of stimulant
      medications, primarily by inadequate provision of information about side effects.
      Coercive use of medications by school systems, in the absence of parental
      consent, has raised issues about battery. Constitutional questions are present
      concerning limitations on parental rights to decline medical care for their
      children balanced against the State's interest in safeguarding the health and
      welfare of children. Children's own equal protection, due process, and privacy
      rights are also at issue, as well as their constitutional and statutory right to
      an education.

PMID- 2002218
TI  - A possible pathophysiologic substrate of attention deficit hyperactivity
      disorder.
AB  - The attention deficit hyperactivity disorder (ADHD) is associated with defective
      attention and response inhibition and motor restlessness. Inattention, defective
      response inhibition, and impersistence are more commonly seen in adults with
      right than with left hemisphere dysfunction. In light of this fact and because
      children with ADHD not only appear to demonstrate these symptoms but also neglect
      the left side and have decreased activation of their right neostriatum, we
      propose that these children have a right hemisphere dysfunction. In addition,
      because both inattention and defective response inhibition can be seen in
      children with ADHD and in patients and animals who have frontal lobe and striatal
      dysfunction, we propose that children with ADHD have dysfunction in a right-sided
      frontal-striatal system. Motor restlessness may reflect frontal lobe dysfunction
      due to impairment of the mesocortical dopamine system.

PMID- 2002219
TI  - Chronic low-dose MPTP in nonhuman primates: a possible model for attention
      deficit disorder.
AB  - Schneider and Kovelowski (1990) showed that chronic low-dose N-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine (MPTP) administration to monkeys caused cognitive
      dysfunction without significant motor impairment on tasks thought to be related
      to the caudate-frontal axis. The cognitive difficulties were similar to those
      seen in monkeys with frontal lesions, normal young monkeys, and normal young
      children. The caudate-frontal dysfunction is consistent with the cognitive
      difficulties that are thought to exist in children with attention deficit
      disorder (ADD). The caudate-frontal dysfunction is also consistent with the
      distribution of decreased cerebral blood flow and, presumably, decreased
      metabolism that has recently been found in children with ADD. In monkeys given
      chronic low-dose MPTP, pilot neurochemical studies have suggested abnormalities
      in dopamine and norepinephrine metabolism, the two neurotransmitters most
      frequently linked with ADD. We suggest that chronic low-dose MPTP induced
      cognitive dysfunction in primates may not only be a model for the cognitive
      disturbances that accompany Parkinson's disease but may also aid in understanding
      the cognitive dysfunction seen in children with ADD.

PMID- 2002220
TI  - The role of frontal dysfunction in attention deficit hyperactivity disorder.
AB  - Among diverse populations concerning the etiology of attention deficit
      hyperactivity disorder (ADHD), frontal dysfunction remains strong. The influences
      of frontal systems on attention, particularly the elements of higher mental
      control postulated as prefrontal functions, are illustrated through presentation
      of a number of syndromes of abnormal mental awareness associated with prefrontal
      brain damage. Against this background, a theory explaining part (but not all) of
      the problem seen in ADHD children is postulated, and a firm stand for prefrontal
      dysfunction as one element in the disorder is presented.

PMID- 2002221
TI  - Modern treatment of typhoid fever.

PMID- 2002222
TI  - Tricuspid valve infective endocarditis and pulmonary sepsis due to Erysipelothrix
      rhusiopathiae successfully treated with high doses of ciprofloxacin but
      complicated by gynaecomastia.

PMID- 2002223
TI  - Kingella kingae dactylitis in an infant.

PMID- 2002224
TI  - Ciprofloxacin as an effective antibacterial agent in serratia endocarditis.

PMID- 2002225
TI  - Psoas abscess secondary to brucellosis.

PMID- 2002226
TI  - Yersinia enterocolitica septicaemia in the absence of gastro-intestinal symptoms.

PMID- 2002227
TI  - The effect of Schick testing on diphtheria antitoxin status.
AB  - Twenty-nine healthy persons were Schick tested as part of their occupational
      health examination. All but three of them had been previously immunised against
      diphtheria. One unimmunised person had a history of diphtheria. Blood samples
      were taken before and at varied intervals after the Schick tests in order to
      determine whether the Schick test antigen was immunogenic. Of the 29 persons
      tested, 21 were Schick-negative, three were Schick-positive. Four pseudoreactors
      were Schick-negative, one pseudoreactor was Schick-positive. Only four of the 29
      had any significant rise in antitoxin titre after Schick testing. Three of these
      were Schick-negative, while one was a pseudoreactor who was negative at a later
      reading. We conclude that Schick testing is not reliably immunogenic and that,
      contrary to expectation, it cannot be assumed to elicit a useful booster response
      in previously immunised persons.

PMID- 2002228
TI  - Purulent salpingitis and intra-uterine contraceptive device-related infection due
      to Haemophilus influenzae.

PMID- 2002229
TI  - Diagnostic value of clinical and bacteriological findings in pertussis.
AB  - Clinical and bacteriological findings in the diagnosis of pertussis were
      evaluated in 300 consecutive patients with parental or the patient's own
      suspicion of the disease. Serology was used as a reference method. Of the 285
      (95%) patients fully sampled, 163 (57%) were diagnosed as having pertussis while
      the remaining 122 patients constituted the non-pertussis control group. The
      clinical and epidemiological data were collected at the first visit made on
      median day seven of illness. In this population of mainly unimmunised children,
      the highest predictive values were obtained for the physician's diagnosis of
      pertussis (100%) and for the physician's diagnosis of some other illness (93%).
      The only clinical symptom with a high predictive value for pertussis was the
      report of whoops (92%). Among epidemiological data the highest predictive value
      (90%) was obtained for reported household exposure in unimmunised children more
      than 1 year of age. Culture of Bordetella pertussis was found to have an overall
      50% sensitivity. Isolation of other bacteria had no predictive value in the
      differential diagnosis of pertussis.

PMID- 2002230
TI  - The effect of antimicrobial therapy on mixed infections with Bacteroides species.
      Is eradication of the anaerobes important?
AB  - Antimicrobial agents were used alone or in combinations in order to explore their
      effect on mixed aerobic-anaerobic infections. Subcutaneous abscesses were induced
      in mice by single and mixed infections of Bacteroides fragilis, Bacteroides
      melaninogenicus, Staphylococcus aureus, Streptococcus pyogenes, Streptococcus
      faecalis, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa. The
      infected animals were treated for 5 days with spiramycin, gentamicin or
      metronidazole alone, or metronidazole combined with spiramycin or gentamicin.
      Animals were killed 5 days after inoculation and the bacterial contents of the
      abscesses determined. Infection induced by a single species of bacteria always
      responded to appropriate antimicrobial therapy. In infections caused by two
      species of organisms, however, therapy directed at either the Bacteroides sp.
      (with metronidazole) or the aerobes or facultative anaerobes (with spiramycin or
      gentamicin) was effective not only in significantly reducing the numbers of the
      target organism but also, in 13 of 24 instances, in reducing to a small extent
      the numbers of the other bacteria. Despite this phenomenon, in no instance did
      therapy with a single agent eliminate the infection and eradicate the untargeted
      organism. The combination of spiramycin and metronidazole increased the reduction
      in numbers of B. melaninogenicus in single-organism infections and of Bacteroides
      sp. in mixed infections with S. aureus and S. pyogenes. These findings support
      the need to aim treatment at all components of mixed infections.

PMID- 2002231
TI  - Long-term antimicrobial therapy in the prevention of recurrent soft-tissue
      infections.
AB  - Thirty-six patients who had suffered two or more episodes of erysipelas or
      cellulitis during the previous year were randomly divided into two equal groups;
      one group received erythromycin base 250 mg b.i.d. for 18 months, while the other
      group received no prophylaxis for a similar period. No patients in the treated
      group developed infection during the 18 months' follow-up but eight of the
      control group (50%) relapsed and required antibiotic treatment. Prolonged
      antimicrobial prophylaxis is effective and safe in preventing recurrent episodes
      of soft-tissue infections.

PMID- 2002232
TI  - Maternal listeriosis in pregnancy without fetal or neonatal infection.
AB  - Maternal infection with Listeria monocytogenes without fetal or neonatal
      involvement is relatively rare. Eleven cases arising in England and Wales between
      1967 and 1988 are presented.

PMID- 2002233
TI  - Humoral immune response to pneumococcal antigen 23-F in an asplenic patient with
      recurrent fulminant pneumococcaemia.
AB  - Host defence mechanisms were analysed in a patient with three episodes of
      fulminant pneumococcaemia and one episode of bacteraemic epiglottitis with
      Haemophilus influenzae type b. The first episode took place 11 years after
      splenectomy for blunt abdominal trauma. Investigations revealed several host
      defence mechanisms to be impaired. In addition to the patient's asplenia, an
      inherited C2-deficiency was noted. Assessment of IgG subclasses repeatedly
      revealed markedly low IgG4 concentrations. These were not due to an increased
      turnover of IgG4, as could be shown following infusion of intravenous IgG. In
      addition, IgG2 concentrations were low in the patient who lacked G2M(23). Opsonic
      mediating antibodies against type 23-F pneumococci were in the range of those of
      non-immune volunteers 6 months after vaccination with a 23-valent pneumococcal
      vaccine. These antibodies did not increase after a septic episode with 23-F
      capsular-type pneumococci. Neutrophil function was apparently normal.

PMID- 2002234
TI  - An outbreak of psittacosis.
AB  - An outbreak of chlamydia infection affecting seven people from a small town in
      Grampian is described. The origin of the outbreak seemed to be a local pet shop.
      The difficulties of diagnosis and tracing the connections with the pet shop are
      discussed. The clinical histories of the seven patients are described including
      those of the two who died.

PMID- 2002235
TI  - Pneumococcal meningitis in a child with a ventriculo-peritoneal shunt.
AB  - A case of pneumococcal meningitis in an infant with a ventriculo-peritoneal shunt
      is reported. There was initial failure of treatment with penicillin and
      cefotaxime in full dosage. Eradication of infection without shunt removal was
      eventually achieved by adding rifampicin to the antibiotic regime.

PMID- 2002236
TI  - Tick-borne encephalitis complicated by monoplegia and sensorineural deafness.
AB  - Tick-borne encephalitis (TBE) is rarely seen in Britain. We report a case of TBE
      in a 44-year-old Swedish woman presenting to an accident and emergency department
      in London. The clinical features of the case, while in many ways typical, were
      nonspecific and led to difficulty in early diagnosis. The course of the illness
      was complicated by monoplegia and evidence of bulbar involvement with
      sensorineural deafness. The last is a very rare manifestation of TBE. With
      increasing foreign travel, TBE is likely to present more commonly in the U.K. and
      should be considered in any case of febrile illness with neurological
      complications following travel abroad. Serological tests to aid early diagnosis
      should be more readily available.

PMID- 2002237
TI  - An outbreak of Shigella sonnei infection due to contamination of a municipal
      water supply in northern Israel.
AB  - An epidemic of more than 8000 cases of Shigella sonnei infection took place in
      four adjacent urban communities which share the same water supply. The epidemic
      was caused by massive faecal contamination of the drinking water due to a leak
      from a broken main sewage pipe into an adjacent drilled well. The infecting
      organism in most cases was S. sonnei colicine type 6, biotype A, which showed a
      high rate of multiple resistance to commonly used antibacterial drugs. Most of
      those affected were children less than 15 years of age. Among adults the attack
      rates were higher in women. Most cases were mild, only 91 patients being admitted
      to hospital. One 5-year-old child died.

PMID- 2002238
TI  - Endocarditis caused by Corynebacterium group D2.

PMID- 2002239
TI  - Surveillance of disease and information on laboratory request forms: the example
      of Legionnaires' disease.

PMID- 2002240
TI  - Urinary tract infection caused by Haemophilus parainfluenzae.

PMID- 2002241
TI  - A problem with oral rifampicin in the prophylaxis of meningococcal infection.

PMID- 2002242
TI  - Chemical modification of Bacillus thuringiensis subsp. thuringiensis (HD-524)
      trypsin-activated endotoxin: implication of tyrosine residues in lepidopteran
      cell lysis.
AB  - A purified protein fraction from a solubilized and trypsin-digested extract of
      Bacillus thuringiensis subsp. thuringiensis (HD-524) fermentation powder was
      lytic to cells from several lepidopteran lines. Maximum yield was obtained by
      alkaline carbonate-thiocyanate solubilization of washed powder followed by
      trypsin digestion and Sephacryl (S-300) chromatography. The alkaline carbonate
      solubilized fraction consisted predominantly of two bands on sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis with MW of 144 +/- 0.9 kDa and 134 +/-
      1.4 kDa. After trypsin treatment and column chromatography, the cytolytic
      fraction consisted of a major band with a MW of 60.0 +/- 1.8 kDa and a minor band
      of 69 +/- 0.9 kDa. Cells from Trichoplusia ni (TN368) were most susceptible to
      lysis with 50% of cells lysed at 3 micrograms/ml, followed by Spodoptera
      frugiperda cells (SF21AE) exhibiting 50% cell lysis at 5 micrograms/ml and
      Lymantria dispar cells (Ld652Y) showing 40% lysis at 10 micrograms/ml. Chemical
      modification of the polypeptides was performed to determine the role of certain
      amino acid residues in the cytolytic activity. The group-specific reagent
      tetranitromethane was used to nitrate and oxidize tyrosine and cysteine residues,
      respectively. Cysteine residues alone were also modified with p
      hydroxymercuribenzoic acid. Lysine residues were modified with O-methylisourea.
      Of the three types of amino acid residues, only the modification of tyrosine
      resulted in reduced cell lysis.

PMID- 2002243
TI  - rRNA sequence comparison of Beauveria bassiana, Tolypocladium cylindrosporum, and
      Tolypocladium extinguens.
AB  - Five strains of Tolypocladium cylindrosporum, one strain of Tolypocladium
      extinguens, and nine strains of Beauveria bassiana were analyzed using a rapid
      rRNA sequencing technique. The sequences of two highly variable domains (D1 and
      D2) located at the 5' end of the 28S-like rRNA molecule were determined. The
      phylogenetic tree computed from the absolute number of nucleotide differences
      shows the separation between the genus Beauveria and the genus Tolypocladium and
      points out that T. cylindrosporum and T. extinguens probably do not belong to the
      same genus.

PMID- 2002244
TI  - Field and laboratory comparisons of mortality in normal and neoplastic Mya
      arenaria.
AB  - The results of a 6-month mark and recapture experiment involving approximately
      900 adult Mya arenaria demonstrated that under natural conditions, significantly
      higher (P much less than .001, chi 2 test) mortality occurred among animals with
      neoplasia than those diagnosed as normal. Using a blood screening technique, the
      clams were diagnosed and placed in one of three diagnostic groups based on the
      severity of the disease (the percentage neoplastic cells per total number of
      blood cells): Nonneoplastic (NN), 0%; low severity neoplastic (LSN), less than
      50%; and high severity neoplastic (HSN), greater than 50%. Fifty-one percent of
      those clams initially diagnosed as HSN died by the end of the test period as
      compared to 8% of the LSN clams and only 3% of the normals. Both progression and
      remission of the disease were also evident. Approximately 10% of the clams in the
      NN and LSN groups progressed to a LSN or HSN condition, whereas 16% of those
      clams initially identified as LSN, and that were recovered alive, underwent
      complete remission during the test period. Comparison of the field results with
      those of an 18-week laboratory study suggests that studies of mortality done
      under laboratory conditions may not provide useful data for the interpretation of
      the quantitative effects of a disease process, such as molluscan neoplasia, on
      the natural population of the animal studied.

PMID- 2002245
TI  - Construction of tracer plasmids for Bacillus sphaericus 1593 utilizing the xylE
      gene from Pseudomonas putida.
AB  - Genetically engineered microorganisms (GEMS) released into the environment must
      be traceable in order to accurately assess their impact on the area of release.
      Tracer genes other than those that introduce antibiotic resistance are preferred
      for use in identifying genetically engineered strains. In this study, we describe
      the construction of a series of tracer plasmids for use in Bacillus sphaericus
      using the xylE gene from the Pseudomonas putida TOL plasmid. This gene codes for
      the enzyme catechol 2,3-dioxygenase which converts the colorless substance
      catechol to 2-hydroxymuconic semialdehyde, a yellow product which is easily
      detected. Colonies of cells which express the xylE gene turn yellow shortly after
      being exposed with a solution of catechol.

PMID- 2002246
TI  - Peptide mapping of different Bacillus thuringiensis toxin gene products by CNBr
      cleavage in SDS-PAGE gels.
AB  - A cyanogen bromide fragmentation reaction of 3 hr in sodium dodecyl sulfate gel
      slices was used for the degradation of the toxins coded by the three cryIA genes
      from Bacillus thuringiensis kurstaki. Peptide patterns diagnostic for each toxin
      gene product were observed. Treatment longer than 3 hr led to the weakening and
      disappearance of protein bands. In 9 out of 16 wild B. thuringiensis strains
      tested, it was determined that only one of the cryIA genes was being expressed;
      in 6 strains, one to two genes were identified, with the presence of an
      additional gene possible and masked because of the overlap of peptide bands; in
      one strain none of the genes was expressed.

PMID- 2002247
TI  - Biochemical diagnosis of systemic mast cell disorders.
AB  - Systemic mastocytosis is characterized by an abnormal proliferation of tissue
      mast cells. Symptoms of mastocytosis are primarily attributed to the release of
      mast cell mediators during episodes of systemic activation of the excessive
      numbers of mast cells. Thus, biochemical evidence for the release of increased
      quantities of mast cell secretory products can suggest or confirm, depending on
      the clinical situation, a diagnosis of systemic mastocytosis. A major advantage
      of the biochemical approach to the diagnosis of systemic mast cell disease is
      that it has allowed the recognition of a class of patients in whom episodes of
      systemic mastocytes activation can be unequivocally documented biochemically but
      in whom clear-cut evidence of abnormal mast cell proliferation is lacking by
      current histologic criteria. Although the release of increased quantities of mast
      cell mediators can be demonstrated during episodes of mast cell activation in
      such patients, mediator levels are usually normal at quiescent times. By
      contrast, patients with proliferative mast cell disease (mastocytosis) usually
      exhibit chronic overproduction of mast cell mediators. Mast cell secretory
      products that can be measured in an attempt to obtain biochemical evidence of
      systemic mast cell activation include histamine, prostaglandin D2, tryptase, and
      heparin. The analytical approaches to assessing release of those individual mast
      cell products are evaluated. In general, the diagnosis and investigation of
      patients with systemic mast cell activation can best be accomplished by concerted
      use of histologic examination of key tissues together with analysis of chemical
      markers of the mast cell.

PMID- 2002248
TI  - Classification and diagnosis of mastocytosis: current status.
AB  - Mastocytosis is a disease characterized by an abnormal increase in mast cells.
      Manifestations of the disease are provoked in large part by the resultant
      increase in mast cell-derived mediators, which have a variety of local and
      systemic effects. Mastocytosis is variable in respect to the organ systems
      involved, clinical manifestations, and association with hematologic diseases.
      This has suggested the need for an improved classification scheme to allow
      assessment of prognosis and therapy. The heterogeneity of the disease patterns in
      mastocytosis strongly suggests that more than one biologic lesion may occur in
      the developmental sequence that leads to placement of mature mast cells in
      tissues.

PMID- 2002249
TI  - Ultrastructural and immunohistochemical characterization of normal mast cells at
      multiple body sites.
AB  - This article reviews the ultrastructural and immunohistochemical features of
      normal human mast cells (MC) at multiple tissue sites. Current literature
      indicates that granules containing discrete scrolls (scroll-rich morphology) are
      frequent in MC from bowel mucosa and lung, locations where the majority of MC
      show only tryptase immunoreactivity (MCT). In contrast, most MC from skin, breast
      parenchyma, axillary lymph nodes, and bowel submucosa are characterized by scroll
      poor morphology (that is, granules are rimmed by incomplete scrolls forming
      parallel lamellae and containing central, amorphous granular material or
      grating/lattice-like structures) and show both tryptase and chymase
      immunoreactivity (MCTC). MC having granules with both scroll-rich and scroll-poor
      features can occur in all tissue sites, and an occasional MC, especially in lung
      and bowel, may show only chymase immunoreactivity (MCC). Chymase immunoreactivity
      in MC also is closely associated with avidin binding and carboxypeptidase
      reactivity. We conclude that there is ultrastructural and immunophenotypic
      diversity among normal human MC, although certain forms predominate in specific
      tissue environments. In skin, breast tissue, axillary lymph nodes, and bowel
      submucosa MC tend to have scroll-poor granules and stain for avidin, chymase,
      tryptase, and carboxypeptidase, whereas, in lung and bowel mucosa MC granules
      tend to be scroll-rich and stain only for tryptase with currently available
      reagents.

PMID- 2002250
TI  - Photoinactivation of T-cell function with psoralen and UVA radiation suppresses
      the induction of experimental murine graft-versus-host disease across major
      histocompatibility barriers.
AB  - Bone marrow transplantation is employed in the treatment of a number of
      hematologic and malignant diseases. A major complication is the induction of
      graft-versus-host disease. Whereas removal of T lymphocytes from the donor marrow
      effectively reduces the incidence of graft-versus-host disease, the incidence of
      graft failure often increases when T cells are depleted from the transplanted
      marrow. In the current study, photoinactivation of the donor cells with 8
      methoxypsoralen coupled with exposure to long-wavelength ultraviolet radiation
      (PUVA therapy) was used to inactivate the response of the donor T cells against
      the host. PUVA therapy suppressed the ability of spleen cells to respond to
      alloantigen in the in vitro mixed lymphocyte reaction. The induction of acute
      graft-versus-host disease across complete major histocompatibility barriers in
      lethally X-irradiated mice was significantly suppressed after bone marrow
      transplantation with photoinactivated bone marrow cells. Long-term survivors
      demonstrated allogeneic reconstitution and partial restoration of T-cell
      function. Because PUVA therapy had no inhibitory effect on hematopoiesis, these
      data suggest that using phototherapy to inactivate the alloreactivity of T cells
      may provide an alternative to purging T cells from the donor marrow, thus
      suppressing both the incidence of graft-versus-host disease and the incidence of
      graft failure.

PMID- 2002251
TI  - Digital cutaneous vascular responses to histamine and neuropeptides in Raynaud's
      phenomenon.
AB  - The pathophysiology of Raynaud's phenomenon is not well defined, but active
      cutaneous microvascular vasoconstriction and emptying must occur to account for
      the pallor and are reasons for studying the microvasculature. It has been
      proposed that there may be a defect in a local histamine vasodilator mechanism.
      The role of the peptidergic nervous system in Raynaud's phenomenon has not been
      previously investigated. To study the histaminergic and peptidergic axes in
      Raynaud's phenomenon, we measured the cutaneous microvascular responses of
      patients with Raynaud's phenomenon to digital intradermal injections of saline,
      histamine, the histamine-releasing agent, compound 48/80, substance P, and
      calcitonin gene-related peptide. We compared these results with those obtained in
      normal subjects. Intradermal cutaneous microvascular blood flow responses were
      quantified by planimetry and laser Doppler flowmetry. The results show: a) that
      in primary Raynaud's phenomenon there is no evidence of local deficiency in
      histamine release or insensitivity to histamine in the cutaneous
      microvasculature; and b) that patients with Raynaud's phenomenon react normally
      to the neuropeptides calcitonin gene-related peptide and substance P, providing a
      rationale for treating Raynaud's phenomenon with vasoactive peptides.

PMID- 2002252
TI  - Localization of basic fibroblast growth factor mRNA in melanocytic lesions by in
      situ hybridization.
AB  - Basic fibroblast growth factor (bFGF) is a mitogen for normal human melanocytes
      and keratinocytes in culture. Experiments in vitro suggest that keratinocytes
      supply bFGF to melanocytes through a paracrine mechanism and that the aberrant
      expression of bFGF in melanomas confers growth independence from bFGF-producing
      cells. To determine whether bFGF is expressed in vivo, we examined a series of
      benign and malignant melanocytic lesions in situ using bFGF riboprobes on tissue
      sections, and correlated bFGF expression with histologic phenotype. Seventeen
      melanocytic neoplasms were studied, including four common acquired nevi, four
      dysplastic nevi, four primary malignant melanomas, and five metastatic melanomas.
      Nevic cells in benign intradermal nevi showed low signal intensity (1+), whereas
      compound and dysplastic nevi showed 2+ to 3+ expression in the junctional nevic
      cell population and 1+ expression in the dermal nevic cell population.
      Melanocytes in primary melanomas had intermediate (2+) and those in metastatic
      melanomas had low (1+) levels of bFGF gene transcripts. Fibroblasts expressed
      high levels (3+) and epidermal and adnexal keratinocytes moderate (2+) levels of
      bFGF in all cases studied. Basic FGF expression in endothelial cells, known to
      produce and respond to this growth factor in vitro, was lower than that in the
      fibroblast and keratinocyte cell population and, in 10 of 17 cases, no bFGF mRNA
      was detectable. This study shows that bFGF is expressed in nevomelanocytes in
      vivo in all melanocytic lesions studied and thus cannot be used as a marker for
      transformation. The presence of bFGF gene transcripts in the various dermal cell
      types and in keratinocytes suggests that it may act as an autocrine and paracrine
      growth factor in regulating cellular proliferation in the skin.

PMID- 2002253
TI  - Barrier function of human keratinocyte cultures grown at the air-liquid
      interface.
AB  - Stratum corneum (SC), the outermost and least permeable layer of skin, is the
      major barrier to passive transepidermal water loss. In the research described in
      this paper, we have used human keratinocyte cultures, grown at the air-liquid
      (A/L) interface, to examine the relationship between epidermal differentiation
      (including SC formation) and barrier function. Histologically, the A/L culture
      showed several markers of complete differentiation, including the presence of
      well-organized and defined epidermal cell layers, keratohyalin granules, and a
      multilayered SC. The permeability of tritiated water through epidermal cultures,
      which had grown for 3 weeks at the A/L interface, was measured with a
      microdiffusion apparatus. The results of these experiments demonstrated that: a)
      the human keratinocyte cultures developed a substantial barrier (i.e., a
      multilayered SC) to water diffusion across the entire surface. If the relative
      humidity of the culturing environment was lowered from 100% to around 75%, the
      barrier was significantly improved; b) the differentiation promoter, 1.25
      dihydroxy-vitamin-D3, increased the number of SC layers and reduced water
      permeation through the culture; c) the nature of the keratinocyte support matrix
      could be altered to improve the morphology as well as the barrier function of the
      epidermal cultures. Overall, the observations are consistent with the
      relationship that is believed to exist between SC intercellular lipid content and
      percutaneous penetration. Confirmation of this hypothesis will further the
      considerable potential of human keratinocyte A/L cultures as a valuable and
      relevant model in which to study drug absorption and metabolism.

PMID- 2002254
TI  - TGF-alpha is widely expressed in differentiated as well as hyperproliferative
      skin epithelium.
AB  - Transforming growth factor-alpha (TGF-alpha) is a potent mitogen for epithelial
      cells that is expressed at low levels in normal epidermis and overexpressed in
      psoriasis. Epidermal growth factor (EGF) has been shown to inhibit hair growth
      but stimulate the growth of sebaceous and sweat glands, suggesting a potential
      role for a member of the EGF/TGF-alpha family in the normal development and
      function of skin appendages as well as epidermis. The present work demonstrates
      TGF-alpha protein in eccrine ducts, and eccrine, sebaceous, and apocrine glands.
      The proliferative dermal hair bulb does not express TGF-alpha in contrast to the
      differentiated outer root sheath hair follicle epithelia. In addition,
      hyperproliferative skin diseases including bullous congenital ichthyosiform
      erythroderma, squamous cell carcinoma, and psoriasis show increased TGF-alpha
      expression. Thus, TGF-alpha may play a role in the morphogenesis and function of
      normal skin appendages and its overexpression is common in benign and malignant
      hyperproliferative skin diseases.

PMID- 2002255
TI  - Proliferating cells in psoriatic dermis are comprised primarily of T cells,
      endothelial cells, and factor XIIIa+ perivascular dendritic cells.
AB  - Determination of the cell types proliferating in the dermis of patients with
      psoriasis should identify those cells experiencing activation or responding to
      growth factors in the psoriatic dermal milieu. Toward that end, sections of
      formalin-fixed biopsies obtained from 3H-deoxyuridine (3H-dU)-injected skin of
      eight psoriatic patients were immunostained, followed by autoradiography.
      Proliferating dermal cells exhibit silver grains from tritium emissions. The
      identity of the proliferating cells could then be determined by simultaneous
      visualization with antibodies specific for various cell types. UCHL1+ (CD45RO+) T
      cells (recall antigen-reactive helper T-cell subset) constituted 36.6 +/- 3.1%
      (mean +/- SEM, n = 6) of the proliferating dermal cells in involved skin, whereas
      Leu 18+ (CD45RA+) T cells (recall antigen naive T-cell subsets) comprised only
      8.7 +/- 1.5% (n = 6). The Factor XIIIa+ dermal perivascular dendritic cell subset
      (24.9 +/- 1.5% of proliferating dermal cells, n = 6) and Factor VIII+ endothelial
      cells (23.0 +/- 2.3%, n = 6) represented the two other major proliferating
      populations in lesional psoriatic dermis. Differentiated tissue macrophages,
      identified by phase microscopy as melanophages or by immunostaining with
      antibodies to Leu M1 (CD15) or myeloid histiocyte antigen, comprised less than 5%
      of the proliferating population in either skin type. In addition to calculating
      the relative proportions of these cells to each other as percent, we also
      determined the density of cells, in cells/mm2 of tissue. The density of
      proliferating cells within these populations was increased in involved versus
      uninvolved skin: UCHL1+, 9.0 +/- 1.7 cells/mm2 versus 1.8 +/- 0.6 cells/mm2, p
      less than 0.01; Factor XIIIa+, 6.0 +/- 0.7 cells/mm2 versus 1.5 +/- 0.5
      cells/mm2, p less than 0.01; Factor VIII+, 5.5 +/- 1.4 cells/mm2 versus 0.0
      cells/mm2, p less than 0.05. The presence of preferential active proliferation of
      a T-cell subset in lesional dermis suggests that activating signals specific for
      this subset are contained within the psoriatic dermis in vivo. The activation of
      recall antigen-reactive T cells may be a driving force behind the dendritic cell
      and endothelial cell proliferation. Alternatively, the selective proliferation
      and expansion of these two constitutive cell types (Factor XIIIa+ and Factor
      VIII+) may result in signals that promote activation of UCHL1+ (CD45RO+) T cells.

PMID- 2002256
TI  - Interleukin-4 promotes the expansion of skin-infiltrating lymphocytes from atopic
      dermatitis in vitro.
AB  - Functional studies of lymphocytes in atopic dermatitis (AD) have so far focused
      on peripheral blood mononuclear cells (PBMC), whereas cells at the involved site,
      the skin, have not been examined. Accordingly, we have developed methods to
      generate lymphocyte cultures from biopsies of inflammatory skin areas. Skin
      infiltrating lymphocytes (SIL) were isolated from skin biopsies of 6 patients
      with severe AD and expanded in vitro in the presence of interleukin-2 (IL-2)
      without additional antigens. After 6-10 d in culture, outgrowth of mononuclear
      cells from biopsy tissue was observed in all cases. Phenotypic analysis of skin
      derived cells revealed the predominance of CD4+ T-helper/inducer phenotype in SIL
      populations. Parallel cultures of SIL and PBMC showed an increase and expansion
      of CD8+ T cells in cultured PBMC, whereas the CD4+ phenotype was predominant in
      SIL cultures. As indicated by their expression of HLA-DR and CD25 antigens, most
      of the SIL were activated and the cells mainly expressed T-cell receptors (TCR)
      composed of alpha and beta chains. Different strategies for expansion of SIL in
      vitro were examined. High levels of IL-4 (1,000 U/ml) in combination with IL-2
      (50 U/ml or 1,000 U/ml) preferentially promoted growth of SIL derived from AD and
      were much more effective than IL-2 alone. No cells expanded in cultures with IL-4
      alone. SIL grown with high concentrations of IL-4 contained a significant
      proportion of double-positive CD4+8+ cells. No other marked differences were
      observed in the distribution of T cell subsets in cultures propagated under
      different conditions for 21 d. Our results demonstrate the feasibility of growing
      infiltrating T lymphocytes from inflammatory skin of AD patients. The use of high
      concentrations of IL-2 in combination with high levels of IL-4 allows a large
      expansion of these cells and thus represents a useful strategy to expand cells
      for further functional and molecular biologic studies.

PMID- 2002257
TI  - Expression of calcyclin, a calcium-binding protein, in the keratogenous region of
      growing hair follicles.
AB  - Changes in calcium levels control the differentiation of skin epithelial cells
      and thus may also affect the epithelial cells of the hair follicle. We have
      isolated a murine cDNA clone, pCAL-F559, for the calcium-binding protein
      calcyclin by differential screening of a cDNA library made from RNA isolated from
      hair follicles of 6-d-old mice. The identity of our cDNA clone was established by
      comparing the DNA sequence with the sequence of the human calcyclin gene. That
      the authentic calcyclin mRNA encoded by pCAL-559 is present in skin of 3-d-old
      mice was confirmed by S1 nuclease protection assays. As measured by RNA dot
      blots, calcyclin mRNA levels in the skin change in accordance with the hair cycle
      and reaches a peak a few days prior to the mRNA for structural hair proteins.
      Although we can demonstrate by in situ hybridization that mRNA for calcyclin is
      localized in the post-mitotic keratogenous region of the hair follicle we can
      only assume that this calcium binding protein is involved in the control of
      differentiation of these cells by regulating their Ca++ levels.

PMID- 2002258
TI  - Intranuclear rodlets and associated true intranuclear bodies in normal cultured
      human dermal papilla cells.
AB  - The dermal papilla is believed to exert controlling influences on hair growth.
      This report documents, for the first time, the occurrence of intranuclear rodlets
      in normal cultured human dermal papilla cells. Intranuclear rodlets have been
      observed predominantly in normal neurons, neural neoplasms, and paraneuromas.
      Whereas intranuclear rodlets and complex intranuclear bodies have not been
      identified in dermal papilla cells in vivo, they were observed, by light
      microscopy and transmission electron microscopy, in primary and subsequent
      passaged cultures in all 10 individuals examined. Intranuclear rodlets and bodies
      were not found, however, in parallel cultures of scalp dermal fibroblasts from
      the same individuals. Rodlet ultrastructure in cultured dermal papilla cells
      exhibited many features in common with previous reports on rodlets in neuronal
      and paraneuronal cells. Features that differentiated the rodlets in this study,
      however, included: doublet/triplet rodlets in the same nucleus; rodlets or
      crystalline filament bundles within complex nuclear inclusions; close
      relationship with the nuclear membrane, and their frequent intimate association
      with intranuclear bodies; and nucleoli and fine chromatin-distinct fibrillar
      material. Although the function of these true intranuclear inclusions in dermal
      papilla cells is unknown, it is noteworthy that they were present in these highly
      metabolically active fibroblasts while absent in comparatively less active dermal
      fibroblasts, and may indeed be a marker for this fibroblast cell type.

PMID- 2002260
TI  - A request for data.

PMID- 2002259
TI  - Heat shock proteins in cultured human keratinocytes and fibroblasts.
AB  - Heat shock induces in cells the synthesis of specific proteins called heat-shock
      proteins. We have compared the induction of these proteins in human
      keratinocytes, skin fibroblasts, and a human epithelial tumor cell line following
      exposure to weak and strong inducing agents (heat, cadmium sulphate, and sodium
      arsenite). The induction of heat shock proteins was measured in cells by one
      dimensional gel electrophoresis of [35S] methionine-labeled proteins and by
      immunofluorescence using a specific HSP72 monoclonal antibody. Both HSP90 and
      HSP116 were constitutively expressed in these cell types. Exposure of these cells
      to weak inducing agents such as heat or cadmium sulphate resulted in the
      synthesis of HSP72 and HSP90, whereas HSP28 and HSP116 synthesis was detected in
      keratinocytes and fibroblasts following exposure to the strong inducing agent
      sodium arsenite. In addition, sodium arsenite induced the synthesis of HSP46 in
      human keratinocytes. Immunofluorescence demonstrated a rapid and reversible
      accumulation of the 72-kD heat shock protein within the nucleolus of heat
      stressed human keratinocytes and fibroblasts.

PMID- 2002261
TI  - The role of the mast cell in clinical gastrointestinal disease with special
      reference to systemic mastocytosis.
AB  - The gastrointestinal tract is a rich source of mast cells with an enormous
      surface area that permits a high degree of interaction between the mast cell and
      intestinal luminal contents. The active metabolic products of the mast cell
      influence gastrointestinal secretion, absorption, and motility through paracrine
      effects of local mast cell degranulation and also cause systemic effects through
      the release of cellular products into the blood stream. Systemic mastocytosis
      influences physiologic function through the systemic effects of mast cell
      products released from focal (e.g., bone marrow) or wide spread increases in mast
      cell number. Local gastrointestinal proliferation of mast cells in response to
      recognized (e.g., gluten in celiac sprue) or obscure stimuli can alter
      gastrointestinal function and induce systemic symptoms. Celiac sprue,
      inflammatory bowel disease, and non-ulcer dyspepsia are three examples of
      gastrointestinal diseases in which mast cells can be implicated in the
      pathophysiology of the symptoms.

PMID- 2002262
TI  - The liver, spleen, and lymph nodes in mastocytosis.
AB  - In systemic mastocytosis the liver, spleen, and lymph nodes may be infiltrated by
      mast cells, with patterns of infiltration specific for each tissue. This may
      result in hepatosplenomegaly and enlarged lymph nodes. Extensive involvement with
      mast cells may also be associated with organ dysfunction. Specifically, in the
      case of liver, mast cell infiltration may result in fibrosis, portal
      hypertension, and abdominal ascites. Clinically significant involvement of the
      liver, spleen, and lymph nodes appears to be more common in patients with
      aggressive forms of mastocytosis, including those with a hematologic disorder.

PMID- 2002263
TI  - Hematologic aspects of mastocytosis: I: Bone marrow pathology in adult and
      pediatric systemic mast cell disease.
AB  - The typical bone marrow lesions seen in adults with systemic mast cell disease
      (SMCD) are foci of spindle-shaped mast cells in a fibrotic matrix and are found
      in up to 90% of adults with SMCD. Lymphocytes and eosinophils frequently are
      admixed with the mast cells, forming the classic MEL lesion. The mast cell
      lesions can be found in perivascular, peritrabecular or intertrabecular locations
      and may on occasion completely replace intratrabecular regions of the marrow. In
      contrast, the mast cell lesions found in children with cutaneous mast cell
      disorders are uniformly small and subtle and are most frequently located
      perivascularly. Lymphocytes, eosinophils, and early myeloid elements may be
      associated with these lesions. Of perhaps greater specificity for SMCD is the
      finding of confluent clusters of mast cells on the marrow aspirates; such
      clusters are noted in up to 30% of patients with SMCD.

PMID- 2002264
TI  - Systemic mastocytosis: retrospective review of a decade's clinical experience at
      the Brigham and Women's Hospital.
AB  - The clinical experience with a group of 21 patients with systemic mastocytosis
      followed at our institution is summarized. Cutaneous and gastrointestinal
      symptoms and findings were the most prominent chronic manifestations; episodic
      vascular collapse was the most dramatic acute event. All patients had indolent
      mastocytosis. There was no mortality.

PMID- 2002265
TI  - Hematologic aspects of mastocytosis: II: management of hematologic disorders in
      association with systemic mast cell disease.
AB  - Individuals with systemic mast cell disease (SMCD) may develop various
      hematologic abnormalities, including cytopenias, myeloproliferative or
      myelodysplastic syndromes, lymphoproliferative syndromes, and primary or
      secondary leukemias. Management of those patients is often complicated by their
      associated hematologic abnormalities. In the case of non-malignant hematologic
      syndromes, the approach to management is supportive. At present, overt
      malignancies are managed with traditional chemotherapy. The presence of leukemia
      in patients with mast cell disease usually indicates a grave prognosis.

PMID- 2002266
TI  - The treatment of mastocytosis: an overview.
AB  - The treatment of mastocytosis requires a recognition of specific disease patterns
      of involvement, with consequent institution of appropriate therapy based on the
      disease pattern manifested in a given patient. Treatment for most forms of
      mastocytosis is conservative and symptomatic. H1 and H2 antihistamines in
      combination or alone remain the primary drugs of choice. In specific cases,
      patients may require aspirin and/or steroids; some must be prepared to self
      administer epinephrine for severe anaphylactic episodes. In patients with
      associated hematologic disorders, the treatment of the disorder will depend on
      the hematologic findings. In rare cases, and in aggressive forms of mastocytosis
      only, it may be necessary to consider limited forms of chemotherapy.

PMID- 2002267
TI  - Granulomatous disease of the larynx.
AB  - Granulomatous diseases of the larynx are discussed with specific emphasis on
      lesions that mimic laryngeal cancer. Nonspecific granulomatous reactions may
      occur from episodes of laryngitis, endotracheal intubation, or chronic abuse of
      the vocal cords. Specific causes are most often of an infectious nature and
      include tuberculosis, syphilis, and fungal infections. Diagnosis and treatment of
      these entities are also addressed.

PMID- 2002268
TI  - Management of early stage endometrial papillary adenocarcinoma.
AB  - This retrospective study examined the outcome in 42 women with early stage (FIGO
      I/II) endometrial adenocarcinoma (papillary, n = 22 and nonpapillary, n = 20). In
      patients with papillary carcinoma, median survival was longer when surgery and/or
      radiotherapy was applied (18 to 36 months) than when such treatment was not used
      or systemic progestational therapy was employed (6 to 9 months). Among those
      evaluable women, the 5-year survival rate was significantly (p = 0.01) better in
      the nonpapillary than the papillary type adenocarcinoma, 45% (9/20) versus 6%
      (1/16) respectively. However, abdominal failure and distant metastasis rates in
      papillary carcinoma were 5% while local recurrence and distant metastasis rates
      in the nonpapillary variety were correspondingly 20% and 15%.

PMID- 2002269
TI  - Nonhemolytic group B streptococcal osteomyelitis: identification and treatment in
      a five-week-old infant.
AB  - This article details the first reported case of neonatal osteomyelitis caused by
      a nonhemolytic group B streptococcus. The identification of the organism was
      delayed due to the lack of hemolysis on blood agar plates. Therefore, the infant
      was treated with a more toxic regimen of antibiotics than would have otherwise
      been indicated. Successful treatment of this nonhemolytic group B streptococcal
      osteomyelitis included a combination of both parenteral and oral antibiotics.
      Proper identification of nonhemolytic streptococcal infections in the infant is
      essential to ensure safe and accurate antibiotic treatment.

PMID- 2002270
TI  - Chemicals, cancer, and risk assessment.
AB  - Cancer rates in Louisiana in particular, and the United States in general,
      especially as they relate to exposure to synthetic chemicals, have been a subject
      of great interest to the general public. Physicians are asked many difficult
      questions on this subject by their patients. This article provides an objective
      overview of cancer mortality rates and cancer risk assessment techniques with the
      intent of assisting physicians in providing knowledgeable responses to these
      questions. Prominent findings contained in this article include: (1) with the
      exception of lung cancer, due to consumption of tobacco products, cancer
      mortality rates are declining; (2) Louisiana ranks 16th among the 50 states in
      overall cancer mortality; (3) cancer risk assessment techniques used by the
      United States government are intentionally very conservative and overestimate
      real cancer risks, particularly for low level exposures; (4) the vast majority of
      cancers is related to individually controllable lifestyle factors; a small
      percentage is related to occupational or environmental exposures.

PMID- 2002271
TI  - ECG of the month. Voila! Dextrocardia.

PMID- 2002272
TI  - Familial amyloidotic cardiomyopathy.

PMID- 2002273
TI  - Of mice and men: insights into the complexity of mononuclear phagocyte system
      blockade provided by autoimmune mouse strains.

PMID- 2002274
TI  - Senile cardiac amyloidosis associated with homozygosity for a transthyretin
      variant (ILE-122).
AB  - Senile cardiac amyloidosis, also known as senile systemic amyloidosis, is a
      sporadic disease of late onset but with increasing incidence with age. Recently
      it has been shown in one case that amyloid deposits contained a transthyretin
      variant with an isoleucine for valine substitution at position 122. A second case
      with the transthyretin isoleucine 122 variant is reported here. This individual,
      who died with restrictive cardiomyopathy, was found to be homozygous for this
      transthyretin variant and his son heterozygous for the variant. A brother of the
      propositus was also homozygous for the variant but died of a cerebral vascular
      accident without being evaluated for amyloidosis. These studies show genetic
      transmission of the isoleucine-122 transthyretin variant associated with this
      form of cardiac amyloidosis.

PMID- 2002275
TI  - Mononuclear phagocyte system dysfunction in murine SLE: abnormal clearance
      kinetics precede clinical disease.
AB  - Although several studies have reported abnormal immune clearance in murine models
      of systemic lupus erythematosus (SLE), a consistent defect in mononuclear
      phagocyte function in SLE-prone mice has not been described. To evaluate the
      mechanism(s) of immune clearance in murine SLE, we applied the technique of
      kinetic analysis to clearance studies of radiolabeled, immunoglobulin-sensitized
      red blood cells in normal BALB/c and autoimmune BXSB, MRL-lpr/lpr, New Zealand
      black (NZB) and New Zealand black/white (NZB/W) mice. Clearance studies were
      performed in 4-week-old to 18-month-old mice with a complement-fixing rabbit IgG
      antimouse red blood cell antibody. Four clearance rate constants governing
      complement- and Fc-mediated clearance function were evaluated: complement
      mediated sequestration (k1), C3b deactivation and release (k2), complement
      dependent phagocytosis (k4), and Fc-mediated sequestration and phagocytosis (k3).
      BXSB male, MRL-lpr/lpr female and male, NZB female, and NZB/W female and male
      mice all had significantly decreased Fc-mediated clearance function (k3) when
      compared with control BALB/c mice (p less than 0.0001). This defect in Fc
      mediated clearance was present in all four strains of autoimmune mice by 6 months
      of age and preceded the onset of serologic and clinical disease activity in NZB
      mice. Abnormal complement-mediated clearance was detected in MRL-lpr/lpr female
      and male mice, NZB female, and NZB/W female and male mice, but not in BXSB mice.
      In MRL-lpr/lpr mice decreased complement-mediated sequestration (k1, p less than
      0.0001) and complement-dependent phagocytosis (k4, p less than 0.0001) were
      present as early as 4 weeks of age. In contrast, the change in complement
      mediated clearance in NZB and NZB/W mice was characterized by decreased C3b
      deactivation and release (k2, p less than 0.001) and resulted in an enhanced
      early phase of clearance. Decreased k2 values in New Zealand mice occurred as
      early as 2 months of age, preceding serologic and clinical disease activity as
      well as decreased Fc receptor function. These studies demonstrated an early,
      progressive, and uniform defect in Fc-mediated clearance in the four murine
      strains of SLE studied. Complement-mediated clearance, however, varied
      considerably in lupus-prone mice, ranging from severe impairment in MRL-lpr/lpr
      to normal function in BXSB and accelerated clearance in NZB and NZB/W mice.
      Accelerated clearance in New Zealand mice was characterized by decreased C3b
      deactivation and release of antibody sensitized cells, which in turn led to
      increased phagocytosis of sensitized cells sequestered by complement-dependent
      processes.

PMID- 2002276
TI  - Evaluation of macrophage procoagulant and fibrinolytic activities induced by
      peritoneal dialysis solutions.
AB  - To investigate the coagulant and fibrinolytic potential of peritoneal
      macrophages, after short-term exposure to dialysis solutions intraperitoneal (IP)
      injection of these hyperosmolar glucose solutions was performed in rats. During
      the 72-hour postinjection period, the dialysis solutions and, as controls,
      Ringer's lactate and Ringer's lactate-glucose all induced a similar increase in
      the number of polymorphonuclear cells and macrophages within a maximum of 24 or
      48 hours after their IP injection. These findings demonstrate that IP injection
      of any dialysis solution results in a moderate non-specific inflammatory cell
      harvesting. Compared with activity induced by the control solutions, no
      significant increase of procoagulant and fibrinolytic activities, identified
      respectively by the presence of thromboplastin and plasminogen activator, was
      observed in peritoneal macrophages obtained 48 hours after injection of the
      solution with the highest glucose concentration. However, the level of
      procoagulant activity could increase as a result of different manufacturers'
      processing of the solutions. That the basal level of macrophage functions may be
      modified suggests that this cell may initiate coagulolytic conditions in the
      peritoneal cavity, especially in the course of IP injection of dialysis
      solutions.

PMID- 2002277
TI  - Inhibition of platelet GPIIb/IIIa binding to fibrinogen by serum factors: studies
      of circulating immune complexes and platelet antibodies in patients with
      hemophilia, immune thrombocytopenic purpura, human immunodeficiency virus-related
      immune thrombocytopenic purpura, and systemic lupus erythematosus.
AB  - We have studied the conditions of in vitro binding of platelet glycoprotein
      IIb/IIIa (GPIIb/IIIa) to fibrinogen and applied the results to identify and
      measure the serum inhibitors to the binding. For the enzyme-linked immunosorbent
      assay, platelet extract was delivered to a fibrinogen-coated microtiter plate
      that was incubated for 2 hours, followed by incubation with anti-GPIIb/IIIa
      monoclonal antibody for another 2 hours. The plate was then incubated with
      peroxidase-conjugated anti-mouse IgG for color development. The binding was shown
      to be calcium-dependent. The binding was partially blocked by treating the coated
      fibrinogen with anti-fibrinogen antibody. Reduction or dissociation of GPIIb/IIIa
      resulted in the total loss of its ability to bind to fibrinogen. Platelet
      extracts of patients with hemophilia showed decreased binding (25% and 14%,
      compared with control platelet extract), and an extract from a patient with
      Glanzmann's thrombasthenia showed no binding. With the enzyme-linked
      immunosorbent assay we have measured serum inhibitors to GPIIb/IIIa binding to
      fibrinogen in 35 hemophilia A, 17 immune thrombocytopenic purpura, 22 human
      immunodeficiency virus-related immune thrombocytopenic purpura, and 29 systemic
      lupus erythematosus serum samples. In those patients with inhibition by serum,
      polyethylene glycol precipitation of circulating immune complexes (CICs)
      decreased the inhibition by the supernatants, and all the resolubilized CIC
      precipitates demonstrated inhibition, which indicates that CICs play a major role
      in the inhibition of GPIIb/IIIa binding to fibrinogen. This, then, provides
      evidence of CIC-mediated impaired GPIIb/IIIa binding to fibrinogen in hemophilia
      A, HIV-ITP, and SLE.

PMID- 2002278
TI  - Evidence for thrombin enhancement of fibrin polymerization that is independent of
      its catalytic activity.
AB  - Inhibition of thrombin proteolysis of fibrinogen with D-phenylalanyl-L-propyl-L
      arginine chloromethyl ketone (PPACK) results in irreversible inactivation of the
      thrombin catalytic site, but the PPACK-inhibited thrombin, through its exosite,
      retains its ability to bind to fibrinogen or fibrin. Hirudin inactivates thrombin
      at the catalytic site and also inhibits thrombin exosite binding to fibrin or
      fibrinogen. PPACK or hirudin was added to a clotting mixture of fibrinogen and
      active thrombin (enzyme-to-substrate ratio = 1:400 at ionic strength of 0.14;
      1:800 at ionic strength of 0.09) before the onset of gelation. Subsequent fibrin
      assembly was evaluated by turbidity measurements at 350 nm and by determining the
      fibrin and fibrinogen content of the clots that ultimately formed. Polymerization
      rates and the fibrin-fibrinogen content of the clots that formed were greater in
      the PPACK-inhibited system than in the hirudin-inhibited system, and the effect
      was amplified at the lower ionic strength. PPACK-thrombin also promoted the
      polymerization of native or prepared mixtures of fibrin and fibrinogen. The
      results suggest that in addition to its well-recognized role in the proteolytic
      conversion of fibrinogen to fibrin, thrombin functions through exosite binding to
      fibrin as a cofactor in fibrin polymerization by accelerating fibrin clot
      assembly.

PMID- 2002279
TI  - A morphometric quantitation of developmental changes in elastic fibers in rat
      lung parenchyma: variability with lung region and postnatal age.
AB  - Elastin has long been thought to play a pivotal role in alveolar septal
      development by providing the structural framework around which new alveoli
      develop in the immature lung. This theory was derived from observations that the
      dramatic increase in lung elastin and alveolar septal development occurred during
      the same time period, days 4 to 13 in the rat. Using stereologic techniques, we
      evaluated volume density of respiratory tissue in parenchyma and total length of
      parenchymal elastic fibers in the lungs of neonatal rats ranging in age from 4 to
      26 days. Lung tissue was obtained from each of the four right lung lobes and from
      the upper, middle, and lower regions of the left lung. When changes in these two
      parameters in the lung as a whole were considered by averaging values for each of
      the seven regions, a continuous increase was observed in both the volume of
      parenchymal tissue in parenchyma and the total length of elastic fibers from days
      4 to 22. A significant correlation was found between the volume of respiratory
      tissue in parenchyma and the length of parenchymal elastic fibers from days 4 to
      26, supporting the existing theory that a causal relationship exists between
      these two parameters. A comparison of the ratios of elastic fiber length to
      volume density of respiratory tissue in parenchyma (Lv/Vrp) from each of the
      seven lung regions sampled indicated a significant variability in Lv/Vrp within
      different regions of the same lung. In addition, the effects of postnatal age and
      lung region on Lv/Vrp were interdependent; the lung regions that differed with
      respect to the length density of elastic fibers varied with postnatal
      age.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2002280
TI  - Direct mitogenic properties of interleukin-1.
AB  - Optimal lymphocyte activation generally requires two concurrent signals, one
      involving the T cell receptor, and another supplied by an accessory cytokine such
      as interleukin-1. We investigated the conditions under which partial cellular
      activation occurs in the absence of signal to the T cell receptor. Both murine
      thymocytes and the T cell clone D10.G4.1 responded to recombinant interleukin-1
      in the absence of a mitogenic signal, although the magnitude of these responses
      was smaller and required higher concentrations of interleukin-1 than if a
      comitogen had been present. Interleukin-1 and interleukin-6 in combination were
      synergistic and induced tritiated thymidine incorporation in D10.G4.1 cells equal
      to 15% of that obtained with optimal concentrations of concanavalin A. Such
      synergy suggests that a significant degree of nonspecific activation of
      lymphocytes may occur in the presence of combinations of monocyte-derived
      cytokines.

PMID- 2002281
TI  - The 1918-1919 influenza pandemic.

PMID- 2002282
TI  - Effect of soluble aminated beta-1,3-D-polyglucose on human monocytes: stimulation
      of cytokine and prostaglandin E2 production but not antigen-presenting function.
AB  - Glucans are insoluble polymers of beta-1,3-linked glucose derived from yeast cell
      walls that effectively activate macrophages. Recently, aminated derivatives of
      beta-1,3-D-polyglucose have been developed that are soluble but also activate
      murine macrophages. The current studies were undertaken to determine whether
      soluble aminated beta-1,3-D-polyglucose (AG) would also stimulate human
      monocytes. The AG employed contained less than 2 ng endotoxin/mg. AG induced the
      production of intracellular, membrane-associated, and secreted forms of
      interleukin 1 (IL1) in a dose-dependent manner, with 50 micrograms/ml yielding
      maximal responses. AG also induced tumor necrosis factor-alpha (TNF alpha)
      secretion by human monocytes. Prostaglandin E2 (PGE2) production was also
      stimulated in a concentration-dependent manner. Quantitatively, optimal
      stimulatory concentrations of AG were comparable to endotoxin in the capacity to
      induce production of these various mediators. In contrast to its capacity to
      induce production of IL1, TNF alpha, and PGE2, AG did not stimulate monocytes to
      become more effective antigen presenting cells. These results indicate that AG is
      potent inducer of proinflammatory mediators from human monocytes but does not
      enhance their capacity to initiate immune responses.

PMID- 2002283
TI  - Neutrophil erythrotoxicity induced by phorbol myristate acetate: mechanisms
      involved in neutrophil activation.
AB  - The capacity of phorbol myristate acetate (PMA) to prime neutrophil cytotoxic
      responses induced by a second stimulus was investigated. Treatment of neutrophils
      with low concentrations of PMA (0.2-0.5 ng/ml) for 18 hr at 37 degrees C markedly
      enhanced cytotoxicity triggered by Ca2+ ionophore A23187, N-formyl-methionyl
      leucyl-phenylalanine (FMLP) and PMA. Pretreatment with PMA also enabled
      neutrophils to mediate significant cytotoxicity when triggered by platelet
      activating factor (PAF), a stimulus unable to induce untreated cells to display
      cytotoxicity. Conversely, neutrophil cytotoxicity triggered by immune complexes
      (IC) was not modified by PMA treatment, whereas cytolytic activity of neutrophils
      against antibody-sensitized target cells was significantly increased. Treatment
      with PMA concentrations higher than 1 ng/ml directly triggered neutrophil
      cytotoxicity. Interestingly, we found that PMA-triggered neutrophils were able to
      sustain maximal levels of cytotoxicity for at least 8 hr after stimulation. With
      regard to the mechanisms involved in neutrophil activation by PMA, we found that
      catalase but not superoxide dismutase (SOD) prevented neutrophil activation
      measured as 1) induction of cytotoxic responses, 2) increase of neutrophil
      adhesiveness to cell-free surfaces, and 3) inhibition of chemotactic responses to
      FMLP. These findings suggest that H2O2 may play a major role in neutrophil
      activation induced by PMA.

PMID- 2002284
TI  - Restoration of prostaglandin releasing macrophage populations in lethally
      irradiated mice with spleen cells from bone marrow-depleted donors.
AB  - Previous studies in mice severely depleted of bone marrow cells by 89Sr showed
      persistent monocytopenia and impaired expression of prostaglandin E2-releasing
      splenic macrophages (PGSM) despite the occurrence in the spleen of more than 10
      fold increases in pluripotential stem cells and M phi colony-forming cells. To
      determine whether the observed deficits were due to a lack of precursors of blood
      monocytes and PGSM in the spleens of 89Sr-treated mice, radiation chimeras were
      established by i.v. infusion of 2 x 10(6) spleen cells from 89Sr donor CBA/J or
      semisyngeneic B6CB F1 hybrid mice into lethally gamma-irradiated CBA/J
      recipients. Blood monocyte levels were greater than normal by day 14 and PGSM
      induced by Corynebacterium parvum were demonstrated by day 28. These restored M
      phi populations expressed the donor haplotype detected in vitro with haplotype
      specific monoclonal anti-H-2K plus complement. 89Sr treatment of the chimeras
      resulted in profound depletion of monocytes and PGSM. The data indicate that the
      spleen of the 89Sr-treated mouse, which is an ineffective source of circulating
      monocytes and PGSM, contains cells which can generate both of these populations
      following infusion into lethally irradiated recipients. Since the bone marrow of
      such recipients was capable of being repopulated, the aggregate observations
      suggest that functional bone marrow is obligatory for the generation of blood
      monocytes and PGSM populations.

PMID- 2002285
TI  - Cyclosporine A induces an early and transient rigidification of lymphocyte
      membranes.
AB  - The effect of cyclosporine A (CsA) on peripheral blood lymphocyte (PBL) membranes
      was studied using fluorescence techniques. Light scattering and intercalation
      experiments indicate CsA has a critical micelle concentration of 3 x 10(-5) M.
      Doses above this critical concentration were avoided during these in vitro
      studies. Steady-state fluorescence polarization of the lipid probe DPH in
      peripheral blood lymphocyte membranes revealed that 10(-5) M CsA caused a
      significant increase in the fluorescence polarization 1-5 min after exposure (15
      16% above control DPH polarization values). This initial increase in polarization
      plateaued at 10-11% above control values within roughly 40 min. Fluorescence
      lifetime measurements of DPH during this response reveal a slight increase in DPH
      lifetime. The increased DPH lifetimes showed that polarization measurements alone
      underestimate the rigidity of DPH's microenvironment. Measurements of DPH
      polarization and lifetime were analyzed using the Perrin equation to calculate
      the apparent microviscosity. Control PBL membranes at 37 degrees C exhibited a
      microviscosity (eta) equal to 1.89 poise (P). Five to 10 min after CsA exposure
      eta = 2.62-2.68 P and plateaus at eta = 2.31-2.51 P 20-120 min after exposure.
      Dose-response studies show that prolonged (greater than 90 min) exposure to CsA
      alters lymphocyte membrane fluidity. This early response in lymphocytes to CsA
      may correspond to other events associated with the initial binding of CsA to
      lymphocyte membranes such as membrane depolarization and alterations in
      phospholipid metabolism. Intravenous delivery of CsA in clinical studies has
      shown that a similar CsA dose of near 10(-5) M is available in the blood during
      the first hour after injection. The evidence presented here suggests that
      peripheral blood lymphocyte membranes are rigidified when exposed to CsA doses
      similar to those found in patient's blood immediately following intravenous
      administration.

PMID- 2002286
TI  - Legitimacy at the expense of narrowing of scope of practice: chiropractic in
      Canada.
AB  - A number of researchers from Australia, Britain, the United States and Canada
      describe the twentieth century development of chiropractic in terms of increased
      official and public recognition "in exchange for" a narrowing of scope of
      practice claims. This process in Canada is briefly described and is illustrated
      by examining chiropractic's relationships with naturopathy, a broad scope of
      practice health occupation. It is shown that chiropractic in Canada first used
      naturopathy to try to expand its own scope of practice, but then quickly rejected
      any official connections with a broad scope naturopathy in a recent drive to gain
      state recognition for a chiropractic "purified" of its past all-inclusive claims,
      a drive which has been at least partially successful. Yet, this narrowing
      contradicts chiropractic's frequent claims to be a holistic health discipline and
      presents practical problems for chiropractic. While chiropractic is in the
      process of gaining official recognition under proposed health disciplines
      legislation in Ontario, it is faced with dilemmas produced by its contradictory
      claims to narrowing and to holism. At the same time, chiropractic, along with
      many other previously subordinate health occupations, seems to be in the process
      of replacing medical dominance with a broader, but perhaps just as authoritarian,
      regime of "professional dominance." Will success inevitably bring not only an
      implicit acknowledgement of the claims of orthodox medicine, but also a
      separation of chiropractors from patients, those whom chiropractors once made a
      unique claim to serve?

PMID- 2002287
TI  - Chiropractic education: a struggle for survival.
AB  - This paper examines the history of chiropractic education in the province of
      Ontario, Canada, as an example of how the chiropractic profession established
      educational legitimacy. The development of chiropractic education in Ontario
      occurred in two phases. An early phase was poorly organized, leading most
      Canadian chiropractors to seek education in the United States. A second phase was
      instituted in 1945 with the establishment of the Canadian Memorial Chiropractic
      College. The paper discusses developments with the Canadian College.

PMID- 2002288
TI  - Chiropractic in British Columbia: sociopolitical and clinical considerations for
      strategic planning.
AB  - Findings from a major study of chiropractic in British Columbia are used to
      illustrate the nature of limitations that should be considered in planning
      chiropractics future direction. Fifty chiropractors, 60 new clients of
      chiropractors and selected leaders of the chiropractic profession were
      interviewed on a variety of issues. Results indicate that sociopolitical factors
      limiting chiropractic include lack of access to public facilities, absence of
      representation in government services, lack of public funds for research and
      education, limits to reimbursement for services and low social valuation. Nine
      findings are identified as critical to future organizational plans. We suggest
      that a specific planning approach, such as the critical success factor (CSF)
      approach, be considered as a planning framework for organizational success in
      complex sociopolitical environments.

PMID- 2002289
TI  - The sociopolitical development of British chiropractic.
AB  - This paper presents a brief history of British chiropractic and its relationship
      with chiropractic in North America and on the European continent. The relatively
      strong presence of osteopathy as a form of manual medicine and the laissez-faire
      market conditions which Common Law permits alternative health practitioners to
      practice under, regardless of training and qualifications, have historically
      impeded the growth of chiropractic in Britain. Nevertheless, the opening of the
      Anglo-European College of Chiropractic in Bourne-mouth in 1965 has resulted in a
      rapid increase in the number of chiropractors in Britain. The growing interest of
      certain strategic British elites in manipulative therapy as a method for treating
      musculoskeletal problems in the general population is enhancing the legitimacy of
      both chiropractic and osteopathy.

PMID- 2002290
TI  - Sociological studies of the role of the chiropractor: an exercise in ideological
      hegemony?
AB  - This article presents a critique of the concept of marginal role as applied to
      chiropractors by examining the area of structural role theory from which the
      concept has been drawn. It suggests that the concept role was itself a reified
      concept and that its "metaphorical extension" to cover chiropractors constitutes
      a double jeopardy for health scientists. However, since all concepts are
      initially metaphorical ones, a methodology is required for distinguishing
      illegitimate from legitimate usage of metaphors, and reified from nonreified
      metaphors. Such a methodology establishes that: the metaphorical basis of the
      concepts has been lost; Researchers are using the concept role in realist terms;
      the metaphor has a related set of assumptions that are undefended and unexplained
      by role theorists and that have therefore gone "underground"; and the metaphor
      leaves out (suppresses) readily available evidence about the individual and
      society (i.e., is ideological in motive). Further, the article relates this
      process of theoretical reification to the broader social process of reification.
      It suggests that a sociology that proceeds in this way contributes significantly
      to the process of ideological hegemony, and in this instance, to medical
      dominance.

PMID- 2002291
TI  - Calcification of vas deferens associated with diabetes mellitus.
AB  - Calcification of the vas deferens may be associated with diabetes mellitus. This
      paper discusses the case of a patient in which this occurred. In clinical
      practice, this radiological finding may indicate further diagnostic workup for
      diabetes or other causative conditions which are described here.

PMID- 2002292
TI  - Effects of chiropractic treatment on blood pressure and anxiety: a randomized and
      controlled trial.

PMID- 2002293
TI  - Humor: interexaminer reliability of the innatometer.

PMID- 2002294
TI  - A critical look at the subluxation hypothesis.

PMID- 2002295
TI  - Addressing the issue of cataloging and making chiropractic literature accessible:
      Part I. Defining the problem.

PMID- 2002296
TI  - Interexaminer concordance in detecting joint-play asymmetries revisited.

PMID- 2002297
TI  - Differential effects of honey, sucrose and fructose on blood sugar levels.

PMID- 2002298
TI  - Response specificity in animal timing.
AB  - The stimuli that control responding in the peak procedure were investigated by
      training rats, in separate sessions, to make two different responses for food
      reinforcement. During one type of session, lever pressing was normally reinforced
      32 s after the onset of a light. During the other type of session, chain pulling
      was normally reinforced either 8 s after the onset of one auditory cue or 128 s
      after the onset of a different auditory cue. For both types of sessions, only the
      appropriate manipulandum was available, and 20% of the trials lasted 240 s and
      involved no response-contingent consequences. Rats were then tested with the
      auditory cues in the presence of the lever and the light in the presence of the
      chain. If the time of reinforcement associated with each stimulus was learned,
      response rates should peak at these times during transfer testing. However, if a
      specific response pattern was learned for each stimulus, little transfer should
      occur. The results did not clearly support either prediction, leading to the
      conclusion that both a representation of the time of reinforcement and the rat's
      own behavior may control responding in this situation.

PMID- 2002299
TI  - Substitutability between conditioned and primary reinforcers in discrimination
      acquisition.
AB  - Rats and pigeons were trained on a series of reversals of a conditional
      simultaneous discrimination. The percentage of reinforcement for correct trials
      was varied across reversals. When nonreinforced correct trials produced the same
      feedback as incorrect trials, the number of errors to reach an acquisition
      criterion was greater for smaller percentages of reinforcement, but the number of
      reinforcers required was either approximately constant or smaller for the smaller
      percentages. When a stimulus paired with food (the conditioned reinforcer) was
      added on nonreinforced correct trials, both measures were substantially
      decreased. When the same stimulus was presented, but without a history of food
      pairing, learning rate was similar to when no stimulus was presented on
      nonreinforced trials. The results provide direct evidence that conditioned
      reinforcers may substitute, although imperfectly, for a primary reinforcer, and
      that pairing with the primary reinforcer is a necessary condition for such
      substitutability to occur.

PMID- 2002300
TI  - Effects of discrete-trial and free-operant procedures on the acquisition and
      maintenance of successive discrimination in rats.
AB  - Rats were trained on a successive discrete-trial discrimination between two tonal
      stimuli to examine the effects of availability of a lever during intertrial
      intervals. In the discrete-trial condition, in which a lever was removed from the
      chamber during intertrial intervals, 10-s trials were initiated by the
      presentation of both discriminative stimulus and lever. In the free-operant
      condition, in which a lever was present during both trials and intertrial
      intervals, 10-s trials were initiated only by the presentation of a
      discriminative stimulus. Experiment 1 employed 50-s intertrial intervals and
      demonstrated that discriminative performances were acquired faster and maintained
      better in the free-operant conditions than in the discrete-trial conditions.
      Experiment 2 employed 5-s intertrial intervals and showed that poor
      discriminative performances in the discrete-trial conditions were improved. These
      results indicate that the presentation of a lever to start a trial can overshadow
      or mask the control by a discriminative stimulus and thereby obstruct the
      acquisition and maintenance of discriminative performances. Furthermore, the
      overshadowing or masking effects are strengthened as a function of the duration
      of intertrial intervals.

PMID- 2002301
TI  - Preference for conditioned reinforcement.
AB  - Pigeons were presented with a concurrent-chains schedule in which both choice
      alternatives led to the same terminal-link stimulus, which was followed by food.
      Superimposed on the food-reinforced presentations of the terminal-link stimulus
      was a second schedule of presentations of the same stimulus that were followed by
      no food. The absolute number of these no-food stimulus presentations was held
      constant while their relative frequency assigned to one or the other choice
      alternative was systematically varied. Preference for a given choice alternative
      tracked the relative frequency of these stimulus presentations, thus
      demonstrating that they served as reinforcers. These results resolve conflicts in
      the literature regarding the effect of conditioned reinforcement on choice.

PMID- 2002302
TI  - Choice with probabilistic reinforcement: effects of delay and conditioned
      reinforcers.
AB  - Two experiments measured pigeons' choices between probabilistic reinforcers and
      certain but delayed reinforcers. In Experiment 1, a peck on a red key led to a 5
      s delay and then a possible reinforcer (with a probability of .2). A peck on a
      green key led to a certain reinforcer after an adjusting delay. This delay was
      adjusted over trials so as to estimate an indifference point, or a duration at
      which the two alternatives were chosen about equally often. In all conditions,
      red houselights were present during the 5-s delay on reinforced trials with the
      probabilistic alternative, but the houselight colors on nonreinforced trials
      differed across conditions. Subjects showed a stronger preference for the
      probabilistic alternative when the houselights were a different color (white or
      blue) during the delay on nonreinforced trials than when they were red on both
      reinforced and nonreinforced trials. These results supported the hypothesis that
      the value or effectiveness of a probabilistic reinforcer is inversely related to
      the cumulative time per reinforcer spent in the presence of stimuli associated
      with the probabilistic alternative. Experiment 2 tested some quantitative
      versions of this hypothesis by varying the delay for the probabilistic
      alternative (either 0 s or 2 s) and the probability of reinforcement (from .1 to
      1.0). The results were best described by an equation that took into account both
      the cumulative durations of stimuli associated with the probabilistic reinforcer
      and the variability in these durations from one reinforcer to the next.

PMID- 2002303
TI  - The relationship between feeding rate and patch choice.
AB  - Rats in a laboratory foraging simulation searched for sequential opportunities to
      feed in two patches that differed in the rate at which food pellets were
      delivered (controlled by fixed-interval schedules) and in the size of the
      pellets. The profitability of feeding in each patch was calculated in terms of
      time (grams per minute) and in terms of effort (grams per bar press). These
      values were the result of the imposed fixed interval, the size of the pellets,
      and the rate at which the rats pressed the bar in each condition. The rats ate
      more food and larger meals, but not more frequent meals, at the patch offering
      the higher rate of food consumption, calculated as grams per minute. The relative
      intake at any patch was a function of the relative rate of intake during meals at
      that patch compared to the other patch. Rats respond to explicit manipulations of
      feeding time in the same manner as they respond to manipulations of feeding
      effort.

PMID- 2002304
TI  - Chunking during serial learning by a pigeon: III. What are the necessary
      conditions for establishing a chunk?
AB  - What are the minimal conditions for the formation of chunks by a pigeon learning
      an arbitrary list? Experiment 1 compared the acquisition of two types of
      chunkable list (each composed of colors and achromatic geometric forms): A----B--
      -C----D'----E' (or A'----B'----C'----D----E) and A----B----C'----D'----E' (or A'-
      --B'----C----D----E). The first type of list was acquired more rapidly than the
      second. On both lists, however, evidence of chunking did not emerge until the
      four-item phase of training (e.g., pauses at the end of one category of list
      item). In Experiment 2, chunking was shown to occur on four-item lists in which
      colors and forms were segregated (A----B----C'----D' and A'----B'----C----D), but
      not on lists in which the two types of items were interspersed (A----B'----C'---
      D and A'----B----C----D'). As in Experiment 1, evidence of chunking (pauses at
      chunk boundaries) did not appear until the fourth item was added.

PMID- 2002305
TI  - Temporal specificity in cross-modal transfer of the rabbit nictitating membrane
      response.
AB  - Two experiments examine cross-modal transfer of response features specific to the
      interstimulus interval (ISI) between a conditioned stimulus (CS) and an
      unconditioned stimulus. Rabbits were given initial training with a stimulus (CSA)
      in one modality (e.g., tone) at a designated ISI (e.g., 600 ms). Training was
      then shifted to a new stimulus (CSB) in another modality (e.g., light) at a new
      ISI (e.g., 400 ms). The timing of early conditioned responses (CRs) to CSB
      reflected the ISI of CSA. Ultimately, CRs to CSB shifted to a temporal location
      conforming to the ISI of CSB. When the ISI of CSB was shorter than that of CSA,
      CRs to CSA also shifted to a locus conforming to the ISI of CSB. The present
      results confirmed previous findings that training in one CS modality accelerates
      CR acquisition to a CS in another modality. The findings are compared with the
      transfer of response patterns in instrumental learning sets and are discussed
      regarding their implications for theories of cross-modal transfer.

PMID- 2002306
TI  - Attention in humans and animals: is there a capacity limitation at the time of
      encoding?
AB  - Investigators have suggested that pigeons have a limited capacity input channel
      and that as a result performance suffers when information load is great. This
      information overload hypothesis is based on converging findings from experiments
      using the matching-to-sample paradigm. Fundamental among these findings are that
      (a) performance improves as sample duration increases, (b) performance is better
      when the sample contains one relevant feature (elements) than when it contains
      two (compounds), and (c) this element superiority effect can be reduced by making
      the relevant feature of compound samples predictable. Experiments 1 and 2 show
      that these effects occur for humans as well. However, Experiments 3, 4, and 5
      show that in humans at least some of these effects do not result from information
      overload at the time of encoding. Thus, the assertion that these effects do
      reflect such a limitation in pigeons must be reevaluated.

PMID- 2002307
TI  - On-line choice and the representation of serially structured stimuli.
AB  - Three groups of pigeons were trained to discriminate between a target temporal
      sequence, consisting of red, green, and blue, and distractor sequences consisting
      of all other combinations of these three colors presented on a pecking key.
      Response alternatives were provided during the course of the trial (on-line
      decisions) as well as the end of the trial (postsequence decisions). Different
      temporal phrasing patterns emphasized the first stimulus in the sequence, the
      final stimulus, or all stimuli equally. The phrasing pattern did not affect the
      speed of acquisition, but groups receiving emphasized stimuli relied more heavily
      on those stimuli than on the other stimuli for their discriminations. The
      patterns of both on-line choices during the sequence and terminal choices
      following the sequence were consistent with the use of hierarchical
      representations and inconsistent with a simple item-by-item prospective
      discrimination scheme.

PMID- 2002308
TI  - Discrimination by pigeons of mixture and uniformity in arrays of stimulus
      elements.
AB  - In 5 experiments, pigeons learned to discriminate uniform arrays of colored
      elements from mixed arrays containing 2 colors in various proportions. When only
      the uniform arrays were positive, mixture-negative gradients were obtained. When
      only the arrays containing equal numbers of red and blue elements were positive,
      mixture-positive gradients were obtained. When elements of different colors from
      2 independent mixture-negative discriminations were recombined, mixture-negative
      gradients were obtained with the transfer patterns. When elements from a mixture
      negative discrimination were combined with a new set of positive elements,
      responding was not suppressed. Appropriate combinations of the elements in
      mixture discriminations reduce responding, but the elements themselves do not
      acquire inhibitory properties.

PMID- 2002309
TI  - Chunking during serial learning by a pigeon: I. Basic evidence.
AB  - Chunking by pigeons was demonstrated by comparing performance on different types
      of lists. Experiment 1 showed that Groups II and IV (who learned lists in which
      colors and achromatic geometric forms were segregated: A----B----C----D'----E'
      and A----B----C----D----E', respectively) executed lists more rapidly than did
      Group I (who learned a homogeneous list of colors: A----B----C----D----E) or
      Groups II and III (who learned lists consisting of unsegregated colors and forms:
      A----B'----C----D'----E and A----B----C'----D----E, respectively). Experiment 2
      showed that Groups II and IV tolerated interruptions of the list better than did
      Groups I, III, and V. The accuracy of responding of Groups I, III, and V
      decreased as a function of the duration of the interruption and the point in the
      sequence at which it occurred. The performance of Group II was unaffected by
      interruptions; Group IV was minimally affected. These results indicate that
      Groups II and IV organized their lists as ordered chunks.

PMID- 2002310
TI  - Chunking during serial learning by a pigeon: II. Integrity of a chunk on a new
      list.
AB  - Can a group of items that a pigeon chunks on one list function as such on a
      second list? In Experiment 1, the ordinal position of the chunk was held constant
      across both lists. Following training on a list of colors and achromatic
      geometric forms (A----B----C----D'----E'), the integrity of the color chunk [A---
      B----C] was maintained on a list of five colors (A----B----C----F----G) even
      though the basis for establishing that chunk was eliminated. The integrity of the
      chunk [A----B----C] was also maintained on a new list of colors and forms (A----B
      ---C----D*----E*). In Experiment 2, the ordinal position of a chunk established
      on list1 (A----B----C'----D') was changed on list 2. As shown by positive
      transfer between lists 1 and 2, the integrity of the chunks [A----B] and [C'---
      D'] was maintained on lists X'----A----B----Y' and X'----C'----D'----Y',
      respectively. Conversely, the heterogeneous list X'----B----C'----Y' took longer
      to learn than the original list.

PMID- 2002311
TI  - Streptococcal toxic shock.

PMID- 2002312
TI  - Office radiographs.

PMID- 2002313
TI  - Out-of-hospital births.

PMID- 2002314
TI  - Stillbirth.

PMID- 2002315
TI  - The roots of public health.

PMID- 2002316
TI  - Prevention of osteoporosis: the role of primary physicians.

PMID- 2002317
TI  - The prevalence of osteoporosis risk factors and physician intervention.
AB  - To determine the prevalence of osteoporosis risk factors and the probability of
      physician risk recognition and intervention, the medical records of a cohort of
      243 women aged 40 to 65 years were reviewed retrospectively. A historical cohort
      design was used. Risk factors present before the start of the study were
      identified. Osteoporosis risk recognition (discussion, problem list),
      osteoporosis specific intervention (counseling about risk, or estrogen or calcium
      supplementation), or nonspecific intervention (dietary, exercise, smoking, or
      alcohol counseling) were recorded over a 3-year follow-up period. Seventy-four
      percent of the women had two or more risk factors. The most common were
      perimenopausal or postmenopausal status (73%) and absence of estrogen
      supplementation (ever) (65%). During the period of the study, 46 women (19%) had
      received an osteoporosis-specific intervention. One hundred eleven women (46%)
      had received one of the above or a less specific intervention. The medical
      records of only 25 women (10%) documented an assessment of osteoporosis risk.
      Only menopausal status predicted osteoporosis intervention, and the probability
      of intervention decreased as the total number of risk factors increased. The data
      identify three groups of women who could benefit from increased risk-reduction
      strategies: premenopausal women, perimenopausal or postmenopausal women who have
      never previously taken supplemental estrogens, and women with multiple risk
      factors.

PMID- 2002318
TI  - Assessment and counseling of coronary risk factors by family practice residents.
AB  - A study was undertaken to determine (1) the likelihood that patients seen for
      episodic health care in a family medical center have been assessed and counseled
      for coronary heart disease (CHD) risk factors, and (2) the likelihood that
      patients having an identified risk factor have been assessed and counseled
      regarding other CHD risk factors. One thousand five hundred twenty-eight medical
      records were randomly selected from all visits occurring over two periods in 1986
      and 1987 to 122 residents in an eight-site family medicine residency network.
      Patients with cardiovascular disease and those younger than 20 or older than 65
      years of age were excluded. Assessments were made of (1) smoking history, blood
      pressure, weight, physical activity, and dietary content during the previous 12
      months; (2) family history of cardiovascular disease during the previous 12
      months and in the initial patient history; (3) and blood cholesterol during the
      prior 5 years. Risk-factor counseling practices were examined for the previous 12
      months. Blood pressure was assessed in 96% of patients, smoking in 40%,
      cholesterol in 26%, and family history in 52%. Ninety-six percent of hypertensive
      patients were counseled for hypertension, but only 45% of smokers and 20% of
      patients with hypercholesterolemia were counseled for those risk factors. Of
      patients having a given risk factor, assessment for any other risk factor
      occurred in fewer than 60% of cases. Patients having a documented positive family
      history were only slightly more likely than other patients to be assessed for
      additional risk factors. There is continued need for enhancing coronary risk
      factor assessment and counseling by resident physicians.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 2002319
TI  - Characteristics of inner-city women giving birth with little or no prenatal care:
      a case-control study.
AB  - Lack of prenatal care has been identified as an important risk factor for poor
      perinatal outcomes. A case-control study was conducted to identify risk factors
      for inadequate prenatal care. Records of women giving birth at an inner-city
      hospital who had fewer than three prenatal visits (cases) were compared with
      those of women giving birth at the same hospital who had more adequate prenatal
      care (controls). The final sample contained 120 women in each group. Women in the
      case group were more likely to be multiparous, to be less educated, and to have
      no telephone in the home. Tobacco and drug abuse were recorded significantly more
      often among these women. There was no difference in racial distribution between
      the case and control groups. Infants of women with minimal or no prenatal care
      had a lower mean birthweight and a higher frequency of prematurity. In logistic
      regression analysis, higher parity, age less than 30 years, single status,
      smoking, drug abuse, and residence in one of two statistical planning areas in
      the city were independently associated with increased odds of not receiving
      prenatal care. To be effective, prenatal outreach programs for inner-city women
      must be based on knowledge of the characteristics and needs of this population.

PMID- 2002320
TI  - Otitis media in day-care children. A report from the International Primary Care
      Network.
AB  - The relationship between day care and acute otitis media and its adverse
      consequences was analyzed as part of a collaborative multinational study. Data
      from primary care research networks in eight countries were collected on 1335
      children, aged 0 to 60 months, at the time of initial visits to their primary
      care physicians for acute otitis media. A history of recurrent acute otitis
      media, poor hearing, and tonsillectomy or adenoidectomy were all more frequent in
      day-care children aged 25 to 60 months, compared with those cared for at home.
      Day-care children were brought to their physicians more promptly after the onset
      of symptoms and received more referrals to otolaryngologists at the time of the
      index visit for acute otitis media. Day care may pose a significant risk for
      otitis media and its adverse consequences.

PMID- 2002321
TI  - Differences in the obstetric practices of obstetricians and family physicians in
      Washington State.
AB  - In response to the obstetric malpractice crisis, both obstetrician-gynecologists
      and family physicians have raised their fees and preferentially selected lower
      risk patients. In addition, large numbers of general and family physicians have
      left obstetric practice altogether. The impact of these responses was explored by
      examining the differences in the demographic and clinical profile of patients
      served by these two disciplines in the State of Washington. Eighty-five percent
      (45,540) of all complete records from 1983 births attended by physicians in the
      State of Washington were matched to physician specialty information. These births
      represent 67% of the total deliveries in Washington State in 1983. Although twice
      as many general and family physicians as obstetricians were practicing
      obstetrics, obstetricians delivered 2.5 times as many infants as did general and
      family physicians. Obstetricians served an older patient population with more low
      birthweight infants, multiple births, and complications of pregnancy than family
      physicians. General and family physicians were more likely to care for
      minorities, teenagers, and unmarried and rural mothers. Obstetricians cared for
      patients with higher medical risks, whereas general and family physicians
      provided care to more socially vulnerable and geographically isolated
      populations. To the extent that general and family physicians are differentially
      abandoning obstetric practice because of the current malpractice crisis, access
      to care for rural and socially vulnerable groups may deteriorate rapidly.

PMID- 2002322
TI  - Cleaning, disinfection, and sterilization of gastrointestinal endoscopes:
      approaches in the office.
AB  - Bacterial contaimination of endoscopes can be clinically significant. While
      current data suggest that flexible sigmoidoscopy may entail fewer risks than
      upper endoscopy, these data are too incomplete to draw this conclusion. Careful
      cleaning and disinfection after each procedure are recommended. Gas sterilization
      of the endoscope and gas or heat sterilization of accessory equipment may be
      necessary in certain clinical situations. It must be remembered that hundreds of
      thousands of endoscopic procedures were performed in the 1970s using cleaning
      only without substantial health risk. The processes do not have to be complicated
      or difficult. Staff must be well trained and must understand the potential risks
      of working with disinfecting agents such as alkaline glutaraldehyde. It is
      recommended that the clinician fully understand the cleaning and disinfection
      steps and be able to perform them. It is important that office procedures be
      based on efficacy, not convenience. The procedures developed to date are not
      ideal and the ideal disinfectant has yet to be found. Cleaning and disinfecting
      machines have been developed, but they are expensive and their efficacy and
      safety are no better than hand-performed methods. An alternative approach to
      reducing transmission of infections by endoscopes may be to seek less adherent
      plastic substances for the endoscope sheath. The introduction of immersible
      endoscopes has helped with cleaning, but their use may also give rise to a false
      sense of security. Diligent attention to cleaning and disinfection is still
      necessary.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2002323
TI  - Preconception care.

PMID- 2002324
TI  - Internal carotid artery thrombosis following penetrating trauma of the soft
      palate: an injury of youth.

PMID- 2002325
TI  - Occurrence of de Quervain's disease in postpartum women.

PMID- 2002326
TI  - I would like a second opinion!

PMID- 2002327
TI  - Graft-versus-host disease.
AB  - Graft-versus-host disease is an uncommon but serious illness, caused by foreign,
      immunocompetent T lymphocytes attacking an immunoincompetent host. It is
      encountered following allogeneic bone marrow transplantation and in congenital
      cellular immunodeficiency disorders. Diagnostic features, clinical grading
      system, therapy and prevention are reviewed.

PMID- 2002328
TI  - Pseudohypoparathyroidism and cerebrovascular disease with dural calcification.
AB  - A 53-year-old woman is reported with recurrent cerebrovascular disease,
      pseudohypoparathyroidism and dural calcification without basal ganglia
      calcification. She had typical clinical and laboratory features of
      pseudohypoparathyroidism and a family history of the condition. One case has been
      reported previously with pseudohypoparathyroidism and Parkinson's disease without
      basal ganglia calcification. Patients with widespread intracranial calcification
      should be evaluated for underlying abnormalities in calcium metabolism. Calcium
      supplementation and administration of vitamin D frequently correct the metabolic
      abnormality and halt clinical progression.

PMID- 2002329
TI  - Practice patterns of obstetricians and gynecologists in Jacksonville, Florida.
AB  - Ninety members of the Jacksonville Obstetrical and Gynecological Society were
      surveyed as to their practice patterns; 55 responded. Due to fear of litigation,
      34% had stopped delivering obstetrical care and 63% plan to discontinue perinatal
      care during the next ten year. At least one malpractice claim had been filed
      against 51%; 9% had two, and 11% three or more. Prenatal and intrapartum testing
      has increased primarily because of fear of litigation. Obstetric fees increased
      44% during the last five years, according to the survey, compared to a Consumer
      Price Index rise of 20%. Mean malpractice premiums rose 42% during the same
      interval.

PMID- 2002330
TI  - Grading is degrading. Doctors' report card.

PMID- 2002331
TI  - Rising medical insurance cost.

PMID- 2002332
TI  - Induction of 5-deiodinase activity in astroglial cells by 12-O
      tetradecanoylphorbol 13-acetate and fibroblast growth factors.
AB  - In the brain, 5'-deiodinase (5'-D) is responsible for the metabolic activation of
      thyroxine (T4) into 3,5,3'-triiodothyronine (T3) and 5-deiodinase (5-D)
      deiodinates T4 and T3 into inactive metabolites. This study examines the effects
      of factors known to induce astroglial 5'-D activity on the 5-D activity in
      cultured rat astroglial cells. The potencies of these factors were compared after
      8 h of incubation, when stimulations by these factors near their maximal effects.
      12-O-Tetradecanoylphorbol 13-acetate (TPA) at 10(-7) M was a potent inducer of 5
      D activity, producing a 30- to 80-fold increase after 8 h. The maximal effect of
      TPA was observed after about 14 h. The TPA stimulation of 5-D activity was not
      dependent on glucocorticoids, unlike 5'-D activity. In comparison with TPA, 8
      bromo-cyclic AMP (10(-3) M) was a poor inducer of 5-D activity whereas it is an
      excellent inducer of 5'-D activity. It produced a 2- to 20-fold increase in 5-D
      activity after 8 h. Natural acidic fibroblast growth factor (20 ng/ml) produced a
      degree of stimulation similar to that of TPA after 8 h. The maximal effect of
      acidic fibroblast growth factor was observed after about 16 h (until a 120-fold
      increase). Recombinant acidic fibroblast growth factor also induced 5-D activity.
      Basic fibroblast growth factor was less potent than acidic fibroblast growth
      factor for increasing 5-D activity (maximal increase by 40- to 50-fold after 8
      h).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2002333
TI  - Autoradiographic imaging of [3H]phorbol 12,13-dibutyrate binding to protein
      kinase C in Alzheimer's disease.
AB  - Quantitative autoradiography was used to examine the distribution of [3H]phorbol
      12,13-dibutyrate ([3H]PDBu) binding to protein kinase C in the middle frontal and
      temporal cortices and the hippocampal region of nine control and nine elderly
      subjects with Alzheimer's disease (AD). AD patients had a clinical diagnosis of
      the disease that was confirmed neuropathologically by the presence of numerous
      plaques in the hippocampus and cerebral cortex. Choline acetyltransferase (ChAT)
      activity was significantly reduced in the middle frontal and temporal cortex and
      in the hippocampus of AD subjects, with the deficit being greater than 60% of
      control values. Quantitative autoradiographic analysis of [3H]PDBu binding to
      protein kinase C revealed a heterogeneous pattern in control brain, being
      particularly high in superficial layers of the cortex and CA1 of the hippocampus.
      There were no significant differences between control and AD sections in all
      areas examined within the middle frontal cortex; e.g., layers I-II control, 491
      +/- 46 versus AD, 537 +/- 39 pmol/g of tissue; middle temporal cortex, e.g.,
      layers I-II control, 565 +/- 68 versus AD, 465 +/- 72 pmol/g of tissue; and
      hippocampal formation, e.g., CA1 control, 511 +/- 28 versus AD, 498 +/- 25 pmol/g
      of tissue. In a parallel study, [3H]PDBu binding to homogenate preparations of
      control and AD brain confirmed that there was no significant difference in
      [3H]PDBu binding in either the particulate or the cytosolic fraction. We have
      demonstrated in a well-defined population of AD patients that [3H]PDBu binding to
      protein kinase C remains preserved in brain regions that are severely affected by
      the neuropathological and neurochemical correlates of AD.

PMID- 2002334
TI  - Effects of chronic nicotinic ligand exposure on functional activity of nicotinic
      acetylcholine receptors expressed by cells of the PC12 rat pheochromocytoma or
      the TE671/RD human clonal line.
AB  - Studies were conducted to ascertain the temporal and dose-dependent effects of
      nicotinic ligand exposure on functional activity of different nicotinic
      acetylcholine receptor (nAChR) subtypes, as expressed by cells of the PC12 rat
      pheochromocytoma (ganglia-type nAChR) or the TE671/RD human (muscle-type nAChR)
      clonal line. Chronic (3-72-h) agonist (nicotine or carbamylcholine) treatment of
      cells led to a complete (TE671) or nearly complete (PC12) loss of functional
      nAChR responses, which is referred to as "functional inactivation." Some
      inactivation of nAChR function was also observed for the nicotinic ligands d
      tubocurarine (d-TC), mecamylamine, and decamethonium. Half-maximal inactivation
      of nAChR function was observed within 3 min for TE671 cells and within 10 min for
      PC12 cells treated with inactivating ligands. Functional inactivation occurred
      with dose dependencies that could not always be reconciled with those obtained
      for acute agonist activation of nAChR function or for acute inhibition of those
      responses by d-TC, decamethonium, or mecamylamine. Treatment of TE671 or PC12
      cells with the nicotinic antagonist pancuronium or alcuronium alone had no effect
      on levels of expression of functional nAChRs. However, evidence was obtained that
      either of these antagonists protected TE671 cell muscle-type nAChRs or PC12 cell
      ganglia-type nAChRs from functional inactivation on long-term treatment with
      agonists. Recovery of TE671 cell nAChR function following treatment with
      carbamylcholine, nicotine, or d-TC occurred with half-times of 1-3 days whether
      cells were maintained in situ or harvested and replated after removal of ligand.
      By contrast, 50% recovery of functional nAChRs on PC12 cells occurred within 2-6
      h after drug removal. In either case the time course for recovery from nAChR
      functional inactivation is much slower than recovery from nAChR "functional
      desensitization," which is a reversible process that occurs on shorter-term (0-5
      min) agonist exposure of cells. These results indicate that ganglia-type and
      muscle-type nAChRs are similar in their sensitivities to functional inactivation
      by nicotinic ligands but differ in their rates of recovery from and onset of
      those effects. The ability of drugs such as the agonists d-TC, decamethonium, and
      mecamylamine to induce functional inactivation may relate to their activities as
      partial/full agonists, channel blockers, and/or allosteric regulators. Effects of
      drugs such as pancuronium and alcuronium are likely to reflect simple competitive
      inhibition of primary ligand binding at functional activation sites.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 2002335
TI  - Decreased release of D-aspartate in the guinea pig spinal cord after lesions of
      the red nucleus.
AB  - This study attempts to determine if fibers that project from the guinea pig red
      nucleus to the spinal cord use L-glutamate and/or L-aspartate as transmitters.
      Unilateral injections of kainic acid were placed stereotaxically in the red
      nucleus to destroy the cells of origin of the rubrospinal tract. Six days after
      the injection, Nissl-stained sections through the lesion site showed that the
      majority of neurons in the red nucleus ipsilateral to the kainic acid injection
      were destroyed. In addition, the lesioned area included parts of the surrounding
      midbrain reticular formation. Silver-impregnated, transverse sections of the
      cervical spinal cord revealed the presence of degenerating fibers contralaterally
      in laminae IV-VII of the gray matter. Ipsilaterally, very sparse degeneration was
      evident in laminae VII and VIII of the gray matter. Two to six days after
      surgery, the electrically evoked, Ca2(+)-dependent release of both D
      [3H]aspartate, a marker for glutamatergic/aspartatergic neurons, and gamma
      amino[14C]-butyric acid ([14C]GABA) was measured in dissected quadrants of the
      spinal cervical enlargement. Lesions centered on the red nucleus depressed the
      release of D-[3H]aspartate by 25-45% in dorsal and ventral quadrants of the
      cervical enlargement contralaterally. The release of [14C]GABA was depressed by
      27% in contralateral ventral quadrants. To assess the contribution of rubro-
      versus reticulospinal fibers to the deficits in amino acid release, unilateral
      injections of kainic acid were placed stereotaxically in the midbrain reticular
      formation lateral to the red nucleus. Nissl-stained sections through the midbrain
      revealed the presence of extensive neuronal loss in the midbrain and rostral
      pontine reticular formation, whereas neurons in the red nucleus remained
      undamaged. In the spinal cord, degenerating axons were present ipsilaterally in
      laminae VII and VIII of the gray matter. Some fiber degeneration was also evident
      contralaterally in laminae V and VI of the gray matter. This lesion did not
      affect the release of either D-[3H]aspartate or [14C]GABA in the spinal cord. The
      substantial decrements in D-[3H]aspartate release following red nucleus lesions
      suggests that the synaptic endings of rubrospinal fibers mediate the release of D
      [3H]aspartate in the spinal cord. Therefore, these fibers may be glutamatergic
      and/or aspartatergic. Because other evidence suggests that rubrospinal neurons
      are probably not GABAergic, the depression of [14C]GABA release probably reflects
      changes in the activity of spinal interneurons following the loss of rubrospinal
      input.

PMID- 2002336
TI  - Interaction of 1-methyl-4-phenylpyridinium ion (MPP+) and its analogs with the
      rotenone/piericidin binding site of NADH dehydrogenase.
AB  - Nigrostriatal cell death in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
      induced Parkinson's disease results from the inhibition of mitochondrial
      respiration by 1-methyl-4-phenylpyridinium (MPP+). MPP+ blocks electron flow from
      NADH dehydrogenase to coenzyme Q at or near the same site as do rotenone and
      piericidin and protects against binding of and loss of activity due to these
      inhibitors. The 4'-analogs of MPP+ showed increasing affinity for the site with
      increasing length of alkyl chain, with the lowest Ki, for 4'-heptyl-MPP+, being 6
      microM. The 4'-analogs compete with rotenone for the binding site in a
      concentration-dependent manner. They protect the activity of the enzyme from
      inhibition by piericidin in parallel to preventing its binding, indicating that
      the analogs and piericidin bind at the same inhibitory site(s). The optimum
      protection, however, was afforded by 4'-propyl-MPP+. The lesser protection by the
      more lipophilic MPP+ analogs with longer alkyl chains may involve a different
      orientation in the hydrophobic cleft, allowing rotenone and piericidin to still
      bind even when the pyridinium cation is in a position to interrupt electron flow
      from NADH to coenzyme Q.

PMID- 2002337
TI  - Positive and negative effects of tacrine (tetrahydroaminoacridine) and
      methoxytacrine on the metabolism of acetylcholine in brain cortical prisms
      incubated under "resting" conditions.
AB  - The effects of tacrine (1,2,3,4-tetrahydro-9-aminoacridine) and 7-methoxytacrine
      on the metabolism of acetylcholine were investigated in experiments on prisms of
      rat cerebral cortex incubated in vitro in low-potassium (3 mmol/L K+) media;
      cholinesterases were inactivated by paraoxon to avoid any action of tacrine and
      methoxytacrine via their inhibition. Under "resting" conditions, tacrine and
      methoxytacrine increased the synthesis of unlabeled acetylcholine in the prisms;
      at the same time, they inhibited the uptake of [14C]choline from the medium and
      the synthesis of [14C]acetylcholine. The concentration of free choline was not
      increased by tacrine or methoxytacrine in either the tissue or the medium. The
      contradiction between the increased synthesis of unlabeled and the diminished
      synthesis of labeled acetylcholine indicates that the utilization of
      intracellular choline (which is presumably mobilized from intracellular choline
      esters) for the synthesis of acetylcholine is increased by tacrine and
      methoxytacrine. This conclusion is supported by the observation that the
      inhibition of acetylcholine synthesis during incubation with hemicholinium-3 (an
      inhibitor of choline transport into cholinergic nerve terminals) was overcome
      when tacrine was present simultaneously with hemicholinium-3. When the prisms
      were preincubated with [14C]choline and incubated with tacrine or methoxytacrine
      only after this, the amount of [14C]acetylcholine recovered in the tissue plus
      the medium was higher at the end of incubation with tacrine or methoxytacrine
      than without them, again suggesting that the drugs were able to increase the
      utilization of intracellular [14C]choline or its esters for acetylcholine
      synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2002338
TI  - Changes in the activity of protein kinase C and the differential subcellular
      redistribution of its isozymes in the rat striatum during and following transient
      forebrain ischemia.
AB  - The changes in the levels of protein kinase C [PKC(alpha, beta II, gamma)] were
      studied in cytosolic and particulate fractions of striatal homogenates from rats
      subjected to 15 min of cerebral ischemia induced by bilateral occlusion of the
      common carotid arteries and following 1 h, 6 h, and 48 h of reperfusion. During
      ischemia the levels of PKC(beta II) and -(gamma) increased in the particulate
      fraction to 390% and 590% of control levels, respectively, concomitant with a
      decrease in the cytosolic fraction to 36% and 20% of control, respectively,
      suggesting that PKC is redistributed from the cytosol to cell membranes. During
      reperfusion the PKC(beta II) levels in the particulate fraction remained elevated
      at 1 h postischemia and decreased to below control levels after 48 h reperfusion,
      whereas PKC(gamma) rapidly decreased to subnormal levels. In the cytosol PKC(beta
      II) and -(gamma) decreased to 25% and 15% of control levels at 48 h,
      respectively. The distribution of PKC(alpha) did not change significantly during
      ischemia and early reperfusion. The PKC activity in the particulate fraction
      measured in vitro by histone IIIS phosphorylation in the presence of calcium, 4
      beta-phorbol 13-myristate 12-acetate, and phosphatidylserine (PS) significantly
      decreased by 52% during ischemia, and remained depressed over the 48-h
      reperfusion period. In the cytosolic fraction PKC activity was unchanged at the
      end of ischemia, and decreased by 47% after 6 h of reperfusion. The appearance of
      a stable cytosolic 50-kDa PKC-immunoreactive peptide or an increase in the
      calcium- and PS-independent histone IIIS phosphorylation was not
      observed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2002339
TI  - Synaptosomal protein kinase C subspecies: A. Dynamic changes in the hippocampus
      and cerebellar cortex concomitant with synaptogenesis.
AB  - The expression of protein kinase C (PKC) subspecies in synaptosomes prepared from
      a number of adult brain regions was compared. Cerebral cortical and
      thalamic/striatal synaptosomes were found to express three peaks of enzyme
      activity upon hydroxyapatite chromatography, corresponding to the type I(gamma),
      type II(beta), and type III(alpha) subspecies. Synaptosomes prepared from either
      the hippocampus or the cerebellar cortex, however, contained only two major
      peaks, corresponding to the alpha- and beta-subspecies, with barely detectable
      levels of the gamma-subspecies, even though these tissue areas were enriched in
      the latter enzyme. When the ontogenic pattern of hippocampal synaptosomal PKC
      subspecies was examined, it was found that at postnatal day 7, significant
      quantities of the gamma-subspecies were present and that this subspecies reached
      its peak levels at around postnatal day 14, before steadily declining to its
      adult level. Similar changes were observed also for the gamma-subspecies in
      cerebellar cortex synaptosomes. The dynamic changes in the synaptosomal PKC
      subspecies take place at a critical period in the development of the rat brain,
      concomitant with an active period of synaptogenesis, suggesting that it may play
      a role in synaptogenesis.

PMID- 2002340
TI  - Synaptosomal protein kinase C subspecies: B. Down-regulation promoted by phorbol
      ester and its effect on evoked norepinephrine release.
AB  - The effect of phorbol esters was investigated on the down-regulation of protein
      kinase C (PKC) and on the release of [3H]norepinephrine (NE) in synaptosomes from
      the rat cerebrum. Treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA)
      promoted the translocation of PKC activity in a P2 fraction from the cytosol to
      the membrane fraction and then its down-regulation, in a dose-dependent manner.
      TPA induced a rapid down-regulation of the type II(beta) and type III(alpha)
      subspecies, but did not change the activity of the type I(gamma) subspecies in
      the cytosolic fraction for at least 15 min. The gamma-subspecies was subsequently
      decreased at a slower rate. In the synaptosomes thus having only the gamma
      subspecies, a subsequent dose of TPA could not enhance K(+)-evoked NE release,
      although, in the original synaptosomes, TPA was able to enhance K(+)-evoked NE
      release. Pretreatment with TPA did not alter the K(+)-evoked NE release itself.
      TPA was also found to enhance the K(+)-evoked NE release from synaptosomes
      prepared from both hippocampus, which express the gamma-subspecies of PKC at a
      negligible level, and cerebral cortex, which have a significant level of the
      gamma-subspecies, to the same degree. These results suggest that the gamma
      subspecies of PKC does not participate in the TPA-enhanced K(+)-evoked NE release
      from synaptosomes.

PMID- 2002341
TI  - Long-term activation of protein kinase C by angiotensin II in cultured bovine
      adrenal medullary cells.
AB  - Previous studies from our laboratory suggest that protein kinase C (PKC) is
      involved in the angiotensin II (AII)-induced increase in the expression of genes
      encoding proenkephalin and catecholamine biosynthesizing enzymes in primary
      cultured bovine adrenal medullary (BAM) cells. The purpose of this study was to
      examine the effects of [Sar1]-AII (S1-AII), an AII agonist, on PKC activity in
      BAM cells. Thirty-minute incubation with S1-AII produced a dose-dependent
      activation of PKC. The particulate PKC activity was significantly increased by 2
      nM S1-AII after both 30 min and 12 h of incubation. A high concentration of S1
      AII (200 nM) caused an increase in particulate PKC activity after 30 min of
      incubation and this increase was still observed after 18 h of continuous
      incubation. [Sar1, Thr8]-angiotensin II (S1, T8-AII) (100 microM), an AII
      antagonist, inhibited the effect of S1-AII (20 nM) on PKC activity, suggesting a
      specific AII receptor-mediated effect. An increase in BAM cell particulate PKC
      immunoreactivity after 18 h of S1-AII treatment was observed in Western blot
      analysis of PKC-immunoreactive protein (82 kDa). The persistent activation of PKC
      seen in this study is consistent with our hypothesis that PKC may mediate the S1
      AII-induced increase in the expression of genes encoding proenkephalin and
      catecholamine synthesizing enzymes in BAM cells.

PMID- 2002342
TI  - Differences in the pharmacokinetics of cocaine in naive and cocaine-experienced
      rats.
AB  - Enhanced cocaine concentrations in brain and blood observed after an
      intraperitoneal challenge dose in rats exposed to cocaine for 10 days by
      subcutaneous administration are traced to a change in the absorption process from
      the site of an intraperitoneal injection to general circulation. This conclusion
      is reached by three sets of corroborating results: (a) Adipose tissue of rats
      treated for 10 days with repeat subcutaneous injections of cocaine did not reveal
      a buildup of cocaine in sufficient concentrations to account for the twofold
      increase in brain and blood concentrations seen during intraperitoneal
      administration; (b) administration of the drug by an intravenous route after 10
      day cocaine treatment did not show a significant difference between treatment and
      control groups; (c) nonlinear regression on the intravenous and intraperitoneal
      data sets using a two-compartment open model indicated a difference in the
      absorption process but not in the metabolic and blood-brain transfer processes.

PMID- 2002343
TI  - Endogenous and expressed angiotensin II receptors on Xenopus oocytes.
AB  - Intact Xenopus oocytes contain a homogeneous population of binding sites for the
      angiotensin II (Ang II) receptor antagonist 125I-[Sarc1,Ile8]-Ang II (125I
      SARILE). Binding of 125I-SARILE to intact oocytes was saturable and of high
      affinity with an apparent KD of 0.7 nM and maximal density of 0.12 fmol/oocyte.
      Binding of 125I-SARILE to oocytes also was specific for Ang II-related peptides
      with a rank order potency of: [Sarc1]-Ang II greater than Ang II greater than Ang
      III much greater than Ang I. However, these endogenous binding sites were present
      only in follicle-enclosed oocytes and within the follicular layer itself. On the
      other hand, injection of poly(A)+ RNA isolated from murine N1E-115 neuroblastoma
      cells into oocytes resulted in the appearance of 125I-SARILE binding sites even
      in defolliculated oocytes. These expressed receptors exhibited pharmacological
      properties similar to those endogenously present in the follicular layer,
      although their levels were much less. Collectively, these results suggest that
      endogenous Ang II receptors are present on Xenopus oocyte follicle cells, whereas
      Ang II receptors expressed from exogenous N1E-115 RNA are found on the oocytes
      themselves. In addition, the high density of Ang II receptors on the follicle
      cells emphasizes the necessity for care in using Xenopus oocytes for the
      expression of receptors encoded by exogenous RNAs.

PMID- 2002344
TI  - Stimulation of phospholipase D activity in human neuroblastoma (LA-N-2) cells by
      activation of muscarinic acetylcholine receptors or by phorbol esters:
      relationship to phosphoinositide turnover.
AB  - We have investigated the coupling of muscarinic acetylcholine receptors (mAChR)
      to phospholipid hydrolysis in a human neuroblastoma cell line, LA-N-2, by
      measuring the formation of 3H-inositol phosphates (3H-IP) and of
      [3H]phosphatidylethanol ([3H]PEt) in cells prelabeled with [3H]inositol and
      [3H]oleic acid. The muscarinic agonist carbachol (CCh) stimulated the
      phospholipase C (PLC)-mediated formation of 3H-IP in a time- and dose-dependent
      manner (EC50 = 40-55 microM). In addition, in the presence of ethanol (170-300
      mM), CCh elevated levels of [3H]PEt [which is regarded as a specific indicator of
      phospholipase D (PLD) activity] by three- to sixfold. The effect of CCh on PEt
      formation also was dose dependent (EC50 = 50 microM). Both effects of CCh were
      antagonized by atropine, indicating that they were mediated by mAChR. Incubation
      of LA-N-2 cells with the phorbol ester phorbol 12-myristate 13-acetate (PMA, 0.1
      microM; 10 min) increased [3H]PEt levels by up to 10-fold. This effect was
      inhibited by the protein kinase C (PKC) inhibitor staurosporine (1 microM) or by
      pretreatment for 24 h with 0.1 microM PMA, by 74% and 65%, respectively. In
      contrast, the effect of CCh on PEt accumulation was attenuated by only 28% in the
      presence of staurosporine (1 microM). In summary, these results suggest that, in
      LA-N-2 neuroblastoma cells, mAChR are coupled both to phosphoinositide-specific
      PLC and to PLD. PKC is capable of stimulating PLD activity in these cells;
      however, it is not required for stimulation of the enzyme by mAChR activation.

PMID- 2002345
TI  - Neurotensin and neuromedin N are differently metabolized in ventral tegmental
      area and nucleus accumbens.
AB  - Whole homogenates and membrane-bound and cytosoluble fractions prepared from rat
      ventral tegmental area (VTA) and nucleus accumbens were examined for their
      content of peptidasic activities and for their ability to metabolize neurotensin
      and its natural related hexapeptide neuromedin N. No qualitative differences were
      observed between these two brain regions concerning the presence and the
      subcellular distribution of a series of activities able to hydrolyze various
      specific fluorimetric enzymatic substrates. However, aminopeptidase B,
      endopeptidase 24-15, and endopeptidase 24-11 were significantly lower in the VTA
      than in the nucleus accumbens membrane preparations, while proline endopeptidase
      was detected in significantly higher amount only in the cytosolic fraction
      prepared from nucleus accumbens. Both neurotensin and neuromedin N were
      metabolized more rapidly in the nucleus accumbens than in the VTA. Furthermore,
      the degradation rate of neuromedin N was considerably faster than that of
      neurotensin whatever the cerebral area examined. Studies carried out with highly
      specific peptidase inhibitors revealed that endopeptidase 24-15 mainly
      contributed to the catabolism of neurotensin in homogenates and membrane-bound
      preparations of nucleus accumbens and VTA, while aminopeptidase B appeared
      predominantly responsible for the rapid disappearance of neuromedin N in both
      cerebral tissues. The possibility that the different metabolic processes of the
      two peptide congeners could explain their distinct pharmacological profiles
      observed after their microinjection in the nucleus accumbens and in the VTA is
      discussed.

PMID- 2002346
TI  - Responsiveness of striatal dopamine release in awake animals after chronic 1
      methyl-4-phenylpyridinium ion-induced lesions of the substantia nigra.
AB  - Extracellular concentrations of dopamine (DA), 3,4-dihydroxyphenylacetic acid
      (DOPAC), and homovanillic acid were measured by microdialysis in rat striatum 1
      month after a unilateral infusion via a dialysis probe of a high concentration
      (10 mM) of 1-methyl-4-phenylpyridinium ion (MPP+) into the substantia nigra. The
      basal extracellular DA concentration at the lesioned side was about 20% of the
      concentration at the nonlesioned side. However, basal DOPAC dialysate levels from
      the lesioned striatum represented only 2.4% of those from the contralateral side.
      Intrastriatal infusion with nomifensine increased the dialysate content of DA
      about twofold and eightfold at the lesioned and nonlesioned sides, respectively.
      Co-infusion of nomifensine with (-)-sulpiride caused an additional pronounced
      rise of the DA output on top of the nomifensine-induced increase at the
      nonlesioned side, whereas no effect was observed at the lesioned side. Finally,
      MPP+ (10 mM) was infused for 45 min into both striata. The increase in the
      dialysate content of DA in response to MPP+ (considered as an index of the total
      striatal DA content) from the lesioned side was only 0.6% of the MPP(+)-induced
      DA increase from the nonlesioned side. A strong compensatory response to
      increased extracellular dopamine was observed in the ipsilateral striatum. This
      effect was achieved by a severe suppression of reuptake mechanisms, as well as of
      the autoreceptor feedback response. It is concluded that infusion of MPP+ into
      the substantia nigra can be used as a chronic biochemical model for clinically
      manifest parkinsonism.

PMID- 2002347
TI  - Postnatal development and isolation of peroxisomes from brain.
AB  - We analyzed the postnatal peroxisome development in rat brain by measuring the
      enzyme activities of catalase and acyl-CoA oxidase and beta-oxidation of [1
      14C]lignoceric acid. These enzyme activities were higher between 10 and 16 days
      of postnatal life and then decreased. We developed and compared two different
      methods for isolation of enriched peroxisomes from 10-day-old rat brain by using
      a combination of differential and density gradient centrifugation techniques.
      Peroxisomes in Percoll (self-generating gradient) banded at a density of 1.036 +/
      0.012 g/ml and in Nycodenz continuous gradient at 1.125 +/- 0.014 g/ml. Acyl-CoA
      oxidase, D-amino acid oxidase, L-pipecolic acid oxidase, and dihydroxyacetone
      phosphate acyltransferase activities and activities for the oxidation of very
      long chain fatty acid (lignoceric acid) were almost exclusively associated with
      catalase activity (a marker enzyme for peroxisomes) in the gradient. The
      postnatal increase in peroxisomal activity with the onset of myelination and the
      presence of enzyme for the biosynthesis of plasmalogens and oxidation of very
      long chain fatty acid (both predominant constituents of myelin) suggest that
      brain peroxisomes may play an important role in the assembly and turnover of
      myelin.

PMID- 2002348
TI  - Fatty acid oxidation and ketogenesis by astrocytes in primary culture.
AB  - The oxidation of the fatty acids octanoate and palmitate to CO2 and the ketone
      bodies acetoacetate and D-(-)-3-hydroxybutyrate was examined in astrocytes that
      were prepared from cortex of 2-day-old rat brain and grown in primary culture to
      confluence. Accumulation of acetoacetate (by mass) in the culture medium of
      astrocytes incubated with octanoate (0.3-0.5 mM) was 50-90 nmol C2 units h-1 mg
      of protein-1. A similar rate was obtained using radiolabeled tracer methodology
      with [1-14C]octanoate as labeled substrate. The results from the radiolabeled
      tracer studies using [1-14C]- and [7-14C]octanoate and [1-14C]-, [13-14C]-, and
      [15-14C]palmitate indicated that a substantial proportion of the omega-terminal
      four-carbon unit of these fatty acids bypassed the beta-ketothiolase step of the
      beta-oxidation pathway and the 3-hydroxy-3-methylglutaryl (HMG)-CoA cycle of the
      classic ketogenic pathway. The [14C]acetoacetate formed from the 1-14C-labeled
      fatty acids, obligated to pass through the acetyl-CoA pool, contained 50% of the
      label at carbon 3 and 50% at carbon 1. By contrast, the [14C]acetoacetate formed
      from (omega-1)-labeled fatty acids contained 90% of the label at carbon 3 and 10%
      at carbon 1, whereas that formed from the (omega-3)-labeled fatty acid contained
      20% of the label at carbon 3 and 80% at carbon 1. These results indicate that
      acetoacetate is primarily formed either by the action of 3-oxo-acid-CoA
      transferase (EC 2.8.3.5) or acetoacetyl-CoA deacylase (EC 3.1.2.11) or both on
      acetoacetyl-CoA and not by the action of the mitochondrial HMG-CoA cycle
      involving HMG-CoA lyase (EC 4.1.3.4), which was readily detected, and HMG-CoA
      synthase (EC 4.1.3.5), which was barely measurable.

PMID- 2002349
TI  - Detection with monoclonal antibodies of a 15-kDa proteolipid in both presynaptic
      plasma membranes and synaptic vesicles in Torpedo electric organ.
AB  - A protein, the mediatophore, has been purified from Torpedo electric organ
      presynaptic plasma membranes. This protein mediates the release of acetylcholine
      through artificial membranes when activated by calcium and is made up of 15-kDa
      proteolipid subunits. After immunization with purified delipidated mediatophore,
      monoclonal antibodies binding to the 15-kDa proteolipid band on Western blots of
      purified mediatophore were selected. A 15-kDa proteolipid antigen was also
      detected in cholinergic synaptic vesicles. Using an immunological assay, it was
      estimated that presynaptic plasma membranes and synaptic vesicles contain similar
      proportions of 15-kDa proteolipid antigen. Detection by immunofluorescence in the
      electric organ showed that only nerve endings were labeled. In electric lobes,
      the staining was associated with intracellular membranes of the electroneuron
      cell bodies and in axons. Nerve endings at Torpedo neuromuscular junctions were
      also labeled with anti-15-kDa proteolipid monoclonal antibodies.

PMID- 2002350
TI  - Effect of cholecystokinin octapeptide on endogenous amino acid release from the
      rat ventromedial nucleus of the hypothalamus and striatum.
AB  - The sulphated octapeptide of cholecystokinin (CCK-8S) was found to cause a dose
      dependent increase in the basal release of aspartate, glycine, and gamma
      aminobutyric acid from the striatum and the ventromedial nucleus of the
      hypothalamus (VMH). No effect on amino acid release was observed after electrical
      (VMH) or potassium (striatum) stimulation. Experiments performed using the CCKB
      selective antagonist L-365,260 and the CCKA-selective antagonist L-364,718
      suggested that this action of CCK-8S was mediated via the CCKB receptor. The
      ability of CCK-8S to evoke amino acid release was not dependent on the presence
      of extracellular calcium, though the effect was abolished by tetrodotoxin.
      Inhibition of protein kinase activity by staurosporine prevented the excitatory
      effects of CCK-8S on amino acid release.

PMID- 2002351
TI  - A role for acetylcholine-nicotinic receptor interactions in the selective
      increase of rat skeletal muscle G4 acetylcholinesterase following short-term
      denervation.
AB  - The present work addresses the effects of short-term denervation on
      acetylcholinesterase (AChE; EC 3.1.1.7) isoenzymes in anterior gracilis muscles
      from adult male Sprague-Dawley rats. It examines possible relationships between
      AChE isoform changes and other denervation phenomena, and evaluates the
      importance of acetylcholine (ACh)-nicotinic receptor interactions in selectively
      modulating the activity of G4 AChE. Results confirm that denervation causes a
      specific, transient increase in G4 AChE and show that: most of the increment can
      be explained by the hydrophobic species of this isoenzyme; changes in AChE
      isoforms markedly precede the onset of spontaneous electromechanical activity
      (fibrillation), as well as acetylcholine receptor (AChR) proliferation; and the
      G4 AChE response is eliminated when AChRs are blocked by alpha-bungarotoxin
      treatment performed before but not after (24 h) denervation. These data point to
      the absence of direct causal relationships between the G4 AChE increment and
      fibrillation, AChR proliferation, or changes in the release of this isoform from
      denervated muscle. In turn, they suggest the participation of AChR activation in
      triggering the G4 AChE response and emphasize the possible role of ACh-AChR
      interactions in modulating the production of this isoenzyme in not only
      denervated but also innervated fast-twitch muscles.

PMID- 2002352
TI  - Carassin: a tachykinin that is structurally related to neuropeptide-gamma from
      the brain of the goldfish.
AB  - A 21-amino-acid residue tachykinin-related peptide, carassin, was isolated in
      pure form from an extract of the brain of the goldfish, Carrassius auratus, by
      reversed-phase HPLC. The primary structure of the peptide was established as the
      following: Ser-Pro-Ala-Asn-Ala-Gln-Ile-Thr-Arg-Lys-Arg-His-Lys-Ile-Asn- Ser-Phe
      Val-Gly-Leu-Met.NH2. This amino acid sequence is the same length as and shows
      structural similarity (57% homology) to the mammalian tachykinin, neuropeptide
      gamma, which is a product of the posttranslational processing of gamma
      preprotachykinin. The mammalian tachykinins, substance P and neurokinin B, were
      not detected in the extract by using specific antisera directed against the NH2
      termini of the peptides, but an antiserum directed against the COOH-terminal
      region of substance P did detect a low concentration of immunoreactive material.

PMID- 2002353
TI  - Widespread distribution of the 14-3-3 protein in vertebrate brains and bovine
      tissues: correlation with the distributions of calcium-dependent protein kinases.
AB  - A highly specific antiserum was prepared against bovine brain 14-3-3 protein, a
      protein kinase-dependent activator of tyrosine and tryptophan hydroxylases. The
      immunoassay using this antiserum proved the presence of 14-3-3 protein in various
      bovine tissues and in brains of various vertebrate species. The quantitative
      analysis indicated that the tissue distribution of 14-3-3 protein is more closely
      related to the known distributions of the Ca2(+)-dependent protein kinases, i.e.,
      Ca2+/calmodulin- and Ca2+/phospholipid-dependent protein kinases, rather than
      those of tyrosine and tryptophan hydroxylases. This result, together with the
      available data on this protein, suggests potential roles of the 14-3-3 protein in
      more diverse kinase-mediated processes than the predicted role in monoamine
      synthesis.

PMID- 2002354
TI  - Differential regulation of corticotropin-releasing factor mRNA in rat brain
      regions by glucocorticoids and stress.
AB  - The regulation of corticotropin-releasing factor (CRF) mRNA expression in the rat
      brain by glucocorticoids and stress was examined by Northern blot analysis and in
      situ hybridization histochemistry. Rats either were exposed to a single
      electrical footshock session and killed 2, 4, 12, or 24 hr later (acute stress),
      or were subjected to the same regimen twice daily for 3 or 7 d and killed on the
      day following the last session (chronic stress). Rats placed in the experimental
      chamber but not administered shock comprised a "sham-handling" group. Chronic (7
      d) intermittent footshock stress resulted in an 84 +/- 26% (P less than 0.05)
      increase in CRF mRNA levels in the whole hypothalamus as detected by Northern
      blot analysis and a 97 +/- 29% (P less than 0.05) increase in the paraventricular
      nucleus (PVN) as detected using in situ hybridization. No significant change in
      CRF mRNA levels was observed in the hypothalamus at any time up to 24 hr after a
      single exposure to footshock stress. A different pattern of results was obtained
      in other CRF-expressing cell groups. In Barrington's nucleus (a pontine
      micturition center), both acute and chronic stress produced significant increases
      in CRF mRNA, while in the olfactory bulb, both paradigms resulted in decreased
      levels. By Northern blot analysis, CRF mRNA in the olfactory bulb declined
      steadily, beginning at 4 hr after acute stress, and reached significance at 24 hr
      (69.2 +/- 1.9% of control, P less than 0.05). Levels from chronically (7 d)
      stressed animals declined to 54.1 +/- 5.1% of control value (P less than 0.05).
      Analysis of hybridization histochemical material revealed that both the number of
      positively hybridized cells and the number of silver grains per cell in the
      mitral and external plexiform layers of the bulb decreased following acute and
      chronic stress. However, CRF mRNA levels in the olfactory bulb were decreased to
      a comparable extent in the sham-handling group, suggesting that exposure to a
      novel environment can effect a decrease in CRF mRNA levels in the olfactory bulb.
      To provide comparisons with the effects of manipulation of glucocorticoid status,
      comparable analyses were carried out in separate groups of animals following
      adrenalectomy (ADX) with and without corticosteroid replacement. After ADX, CRF
      mRNA levels in the whole hypothalamus increased 60 +/- 5% (P less than 0.05) and
      were normalized following dexamethasone replacement. In contrast to the
      hypothalamus, no effects of steroid manipulation on CRF mRNA levels in the
      olfactory bulb, midbrain, cerebral cortex, or brain stem were detected.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 2002355
TI  - Light paired with serotonin in vivo produces both short- and long-term
      enhancement of generator potentials of identified B-photoreceptors in
      Hermissenda.
AB  - An in vivo conditioning procedure consisting of light paired with the direct
      application of 5-HT to the exposed but otherwise intact nervous system of
      Hermissenda produces a long-term modification of phototactic behavior. The long
      term change in phototactic behavior produced by in vivo conditioning is dependent
      upon pairing light with 5-HT. In this paper, we investigate neural correlates of
      in vivo conditioning detected in 2 different identified photoreceptors. We found
      that in vivo conditioning produces a short-term and long-term enhancement of
      light-evoked generator potentials recorded from medial and lateral B
      photoreceptors. We show that short-term enhancement is not dependent upon pairing
      light with 5-HT, is observed in both lateral and medial B-photoreceptors, and is
      expressed by a larger peak and plateau phase of light-evoked generator
      potentials. In contrast to short-term enhancement, we found that long-term
      enhancement is dependent upon pairing light with 5-HT, is detected in only
      lateral B-photoreceptors, and is expressed by a larger steady-state plateau phase
      of light-evoked generator potentials. We also present evidence that the direct
      action of 5-HT interacting with light- and/or voltage-dependent processes is
      sufficient to mimic the effects of in vivo conditioning on long-term enhancement.
      These results suggest that long-term enhancement may contribute to modified
      phototactic behavior in Hermissenda produced by 1-trial in vivo conditioning.

PMID- 2002356
TI  - Expression of diverse neuropeptide cotransmitters by identified motor neurons in
      Aplysia.
AB  - Neuropeptide synthesis was determined for individual identified ventral-cluster
      neurons in the buccal ganglia of Aplysia. Each of these cells was shown to be a
      motor neuron that innervates buccal muscles that generate biting and swallowing
      movements during feeding. Individual neurons were identified by a battery of
      physiological criteria and stained with intracellular injection of a vital dye,
      and the ganglia were incubated in 35S-methionine. Peptide synthesis was
      determined by measuring labeled peptides in extracts from individually dissected
      neuronal cell bodies analyzed by HPLC. Previously characterized peptides found to
      be synthesized included buccalin, FMRFamide, myomodulin, and the 2 small
      cardioactive peptides (SCPs). Each of these neuropeptides has been shown to
      modulate buccal muscle responses to motor neuron stimulation. Two other peptides
      were found to be synthesized in individual motor neurons. One peptide, which was
      consistently observed in neurons that also synthesized myomodulin, is likely to
      be the recently sequenced myomodulin B. The other peptide was observed in a
      subset of the neurons that synthesize FMRFamide. While identified motor neurons
      consistently synthesized the same peptide(s), neurons that innervate the same
      muscle often express different peptides. Neurons that synthesized the SCPs also
      contained SCP-like activity, as determined by snail heart bioassay. Our results
      indicate that every identified motor neuron synthesizes a subset of these
      methionine-containing peptides, and that several neurons consistently synthesize
      peptides that are likely to be processed from multiple precursors.

PMID- 2002357
TI  - Growth of regenerating goldfish axons is inhibited by rat oligodendrocytes and
      CNS myelin but not but not by goldfish optic nerve tract oligodendrocytelike
      cells and fish CNS myelin.
AB  - Encounters of regenerating goldfish retinal axons with oligodendrocytes and CNS
      myelin of mammals and fish were monitored in in vitro assays. Upon contact with
      highly branched rat oligodendrocytes, goldfish axons collapsed or grew around but
      never crossed these cells. However, in the presence of the antibody IN-1 against
      the oligodendrocyte-associated growth-inhibitory proteins, axons did grow over
      highly branched oligodencrocytes. In contrast to the mammalian oligodendrocytes,
      goldfish optic nerve/tract-derived oligodendrocytelike cells allowed the growth
      of axons across their surface and even along their processes. The fish growth
      cones avoided entering the region of rat CNS myelin applied to polylysine/laminin
      coated coverslips or failed to elongate on this substrate. They were, however,
      able to pass over CNS myelin of fish. When exposed to rat CNS myelin as the sole
      substrate, axonal outgrowth from fish retinal explants was inhibited almost
      entirely. However, outgrowth on fish CNS myelin was substantial, but many more
      axons extended on fish or rat brain membranes that were depleted of myelin. Thus,
      goldfish retinal axons are sensitive to the axon-growth-inhibiting cell-surface
      molecules of mammalian oligodendrocytes as well as CNS myelin. Fish optic nerve
      oligodendrocytelike cells and fish CNS myelin lack these inhibitory properties
      and are growth permissive. These in vitro experiments suggest that the success of
      axonal regeneration in the fish optic nerve is causally related to the presence
      of growth-permissive properties and to the absence of growth inhibitors on fish
      optic nerve/tract oligodendrocytelike cells.

PMID- 2002358
TI  - A direct demonstration of functional specialization in human visual cortex.
AB  - We have used positron emission tomography (PET), which measures regional cerebral
      blood flow (rCBF), to demonstrate directly the specialization of function in the
      normal human visual cortex. A novel technique, statistical parametric mapping,
      was used to detect foci of significant change in cerebral blood flow within the
      prestriate cortex, in order to localize those parts involved in the perception of
      color and visual motion. For color, we stimulated the subjects with a
      multicolored abstract display containing no recognizable objects (Land color
      Mondrian) and contrasted the resulting blood flow maps with those obtained when
      subjects viewed an identical display consisting of equiluminous shades of gray.
      The comparison identified a unique area (area V4) located in the lingual and
      fusiform gyri of the prestriate cortex. For motion, blood flow maps when subjects
      viewed moving or stationary black and white random-square patterns were
      contrasted. The comparison identified a unique area located in the region of the
      temporo-parieto-occipital junction (area V5). We thus provide direct evidence to
      show that, just as in the macaque monkey, different areas of the human prestriate
      visual cortex are specialized for different attributes of vision. The striate
      cortex (V1) and the contiguous visual area (V2), which in the monkey brain feed
      both the homologous areas, were active in all 4 conditions. This pattern of
      activity allowed us to use an extension of the approach to assess the functional
      relationship between the 3 areas during color and motion stimulation. This is
      based on an hypothesis-led analysis of the covariance structure of the blood flow
      maps and promises to be a powerful tool for inferring anatomical pathways in the
      normal human brain.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2002359
TI  - The role of GABAergic inhibition in processing of interaural time difference in
      the owl's auditory system.
AB  - The barn owl uses interaural time differences (ITDs) to localize the azimuthal
      position of sound. ITDs are processed by an anatomically distinct pathway in the
      brainstem. Neuronal selectivity for ITD is generated in the nucleus laminaris
      (NL) and conveyed to both the anterior portion of the ventral nucleus of the
      lateral lemniscus (VLVa) and the central (ICc) and external (ICx) nuclei of the
      inferior colliculus. With tonal stimuli, neurons in all regions are found to
      respond maximally not only to the real ITD, but also to ITDs that differ by
      integer multiples of the tonal period. This phenomenon, phase ambiguity, does not
      occur when ICx neurons are stimulated with noise. The main aim of this study was
      to determine the role of GABAergic inhibition in the processing of ITDs.
      Selectivity for ITD is similar in the NL and VLVa and improves in the ICc and
      ICx. Iontophoresis of bicuculline methiodide (BMI), a selective GABAA antagonist,
      decreased the ITD selectivity of ICc and ICx neurons, but did not affect that of
      VLVa neurons. Responses of VLVa and ICc neurons to unfavorable ITDs were below
      the monaural response levels. BMI raised both binaural responses to unfavorable
      ITDs and monaural responses, though the former remained smaller than the latter.
      During BMI application, ICx neurons showed phase ambiguity to noise stimuli and
      no longer responded to a unique ITD. BMI increased the response magnitude and
      changed the temporal discharge patterns in the VLVa, ICc, and ICx.
      Iontophoretically applied GABA exerted effects opposite to those of BMI, and the
      effects could be antagonized with simultaneous application of BMI. These results
      suggest that GABAergic inhibition (1) sharpens ITD selectivity in the ICc and
      ICx, (2) contributes to the elimination of phase ambiguity in the ICx, and (3)
      controls response magnitude and temporal characteristics in the VLVa, ICc, and
      ICx. Through these actions, GABAergic inhibition shapes the horizontal dimension
      of the auditory receptive fields.

PMID- 2002360
TI  - Neuropeptides Gly-Asp-Pro-Phe-Leu-Arg-Phe-amide (GDPFLRFamide) and Ser-Asp-Pro
      Phe-Leu-Arg-Phe-amide (SDPFLRFamide) are encoded by an exon 3' to Phe-Met-Arg-Phe
      NH2 (FMRFamide) in the snail Lymnaea stagnalis.
AB  - Biochemical analysis has shown the pond snail Lymnaea stagnalis to contain 2 main
      classes of Phe-Met-Arg-Phe-NH2 (FMRFamide)-like neuropeptides: the tetrapeptides
      FMRFamide and Phe-Leu-Arg-Phe-NH2 (FLRFamide), and the heptapeptides Gly-Asp-Pro
      Phe-Leu-Arg-Phe-NH2 (GDP-FLRFamide) and Ser-Asp-Pro-Phe-Leu-Arg-Phe-NH2
      (SDPFFRFamide). By genomic mapping and DNA sequencing, we show here that the
      GDP/SDPFLRFamide coding region lies 3' to the FMRFamide coding region. The
      absence of an initiating start methionine and the presence of good-concensus 3'
      and 5' splice sites suggests that the GDP/SDPFLRFamide coding region makes up 1
      exon of a larger gene. In addition to 7 copies of GDPFLRFamide and 6 copies of
      SDPFLRFamide, the exon encoding the heptapeptides also encodes 3 novel peptides,
      Glu-Phe-Phe-Pro-Leu-NH2 (EFFPLamide), Ser-Asp-Pro-Tyr-Leu-Phe-Arg-NH2
      (SDPYLFRamide), and Ser-Asp-Pro-Phe-Phe-Arg-Phe-NH2 (SDPFFRFamide). In contrast
      to the tetrapeptide FMRFamide precursor protein, the GDP/SDPFLRFamide peptides
      are encoded contiguously, being separated only by single basic amino acids.

PMID- 2002361
TI  - A coordinate system for the synthesis of visual and kinesthetic information.
AB  - The results of this study suggest that information derived from kinesthetic
      inputs alone is not normally used to generate an estimate of the location of the
      hand in extrapersonal space. This finding provides support for the interpretation
      of previous results suggesting that a representation of a visual target in
      extrapersonal space must be transformed into a kinesthetic reference frame before
      the parameters of a targeted arm movement can be computed (Soechting and
      Flanders, 1989b). We asked subjects to use a pointer to indicate the spatial
      location of their hand following an unseen passive displacement. We found that
      subjects had large errors in the locations that they chose and that there was a
      large degree of variability for repeated trials with the same hand location. The
      errors were a result neither of using the pointer to indicate a spatial locus nor
      of an inability to make use of kinesthetic information. Instead, the errors
      resulted from an inability of subjects to synthesize an estimate of the hand's
      spatial location from only kinesthetic cues. We also asked subjects to use the
      pointer to indicate the location of their hand following a passive displacement
      when they had visual information about the passive displacement. In this case, we
      found that subjects performed better than when they had only kinesthetic
      information, but not as well as when they had only visual information about
      target location. This finding suggests that kinesthetic information about target
      location affects the processing of visual information.

PMID- 2002362
TI  - Inhibitory effects of brain chondroitin sulfate proteoglycans on neurite
      outgrowth from PC12D cells.
AB  - Soluble chondroitin sulfate proteoglycans (CSPGs), prepared from 10-d-old rat
      brain, were added to the culture medium of PC12D cells containing NGF to examine
      the effects on NGF-induced neurite outgrowth from the cells. PC12D cells, a flat
      shaped variant of PC12 pheochromocytoma cells, are characteristic of prompt
      neurite formation in response not only to NGF, but also to cAMP-enhancing
      reagents such as forskolin. Brain CSPGs inhibited the neurite elongation
      irreversibly in a dose-dependent manner; complete inhibition was observed at a
      concentration of 50 nmol uronic acid/ml. Closely similar dose-dependent
      inhibition was observed in the forskolin-induced neurite outgrowth from PC12D
      cells. NGF-induced neurite outgrowth from conventional PC12 cells was also
      inhibited completely by 50 nmol uronic acid/ml CSPGs. Some brain CSPGs seemed to
      be inhibitory, but the cartilage-unique CSPG did not show any inhibitory effect.
      Chondroitin sulfate, a polysaccharide moiety of CSPGs, did not show any
      inhibitory effect even at a concentration of 250 nmol uronic acid/ml, while core
      proteins prepared from brain CSPGs by digestion with chondroitinase ABC exhibited
      inhibitory activity similar to that of intact CSPGs. This indicates that the site
      of the inhibitory activity exists in the core protein moiety of brain CSPGs. From
      these observations, it is conceivable that brain CSPGs are involved in the
      regulation of neuronal differentiation.

PMID- 2002363
TI  - Interaction of colocalized neuropeptides: functional significance in the
      circadian timing system.
AB  - The suprachiasmatic nucleus (SCN), which appears to act as a circadian clock,
      contains a subpopulation of local circuit neurons in which vasoactive intestinal
      peptide (VIP), peptide histidine isoleucine (PHI), and gastrin releasing peptide
      (GRP) are colocalized. To determine whether VIP, PHI, and GRP interact within the
      SCN to produce a signal important for circadian control, the behavioral and
      cellular effects of coadministration of these neuropeptides were investigated.
      Coadministration of VIP, PHI, and GRP within the SCN mimicked the phase-delaying
      effects of light on circadian control following in vivo microinjection and
      activated SCN single units recorded in vitro. These behavioral and cellular
      effects of coadministration of VIP, PHI, and GRP were significantly greater than
      administration of VIP, PHI, or GRP alone or coadministration of any 2 of these
      peptides. These data illustrate a new mechanism whereby multiple, colocalized
      neuropeptides interact in a functionally significant manner, and indicate that
      the interaction of VIP, PHI, and GRP may be involved in the regulation of
      circadian rhythms by the SCN.

PMID- 2002364
TI  - A mouse brain homolog of the Drosophila Shab K+ channel with conserved delayed
      rectifier properties.
AB  - We have cloned and expressed a mouse brain K+ channel that is the homolog of the
      Drosophila Shab K+ channel. Mouse and Drosophila Shab K+ channels (mShab and
      fShab, respectively) represent an instance of K+ channels and structurally
      related species that are both functionally and structurally conserved; most
      kinetic, voltage-sensitive, and pharmacological properties are similar for the 2
      channels. The greatest functional difference between the currents is recovery
      from inactivation, which is several times slower for mShab than for fShab
      currents. In addition to conserved structure, the mShab polypeptide has an
      unusually long nonconserved region at the carboxyl end of the protein. Truncation
      of 293 residues from the carboxyl end produced no noticeable change in voltage
      sensitive, kinetic, or pharmacological properties. Thus, the measured functional
      properties of mShab are determined by the remaining 564 residues, most of which
      are conserved. The mShab and fShab channels are naturally occurring structural
      variants having substitutions in conserved portions that appear relatively
      neutral with respect to all measured properties except for, possibly, the rate of
      recovery from inactivation. The mShab current closely resembles a native delayed
      rectifier-type potassium current, IK, in hippocampal neurons.

PMID- 2002365
TI  - The temporal profile of 72-kDa heat-shock protein expression following global
      ischemia.
AB  - The potential role of the nonconstitutive 72-kDa heat-shock protein (HSP72) in
      selective neuronal vulnerability to ischemia was studied in rats subjected to
      graded global ischemia. Immunocytochemistry using a monoclonal antibody against
      HSP72 was performed on tissue collected after 24 hr of reperfusion. The
      appearance of HSP72 immunoreactivity correlated in a graded fashion with those
      regions known to be selectively vulnerable in ischemia. That is, HSP72 was
      induced in only hilar interneurons and CA1 pyramidal cells following brief
      ischemia. After intermediate durations of ischemia, HSP72 was expressed in the
      CA3 neurons and cortical layers 3 and 5, and after the longest intervals, HSP72
      appeared in dentate granule cells. Heat-shock protein expression preceded cell
      death (assessed with acid fuchsin staining) in all regions. This temporal profile
      suggests that the capability of neurons to express HSP72 is unlikely to account
      for selective vulnerability of different brain regions following ischemia; its
      role in neuroprotection during ischemic injury in vivo remains unknown.

PMID- 2002366
TI  - Clinical, radiographic, and pathological features of symptomatic Rathke's cleft
      cysts.
AB  - The clinical, radiographic, and pathological findings in 155 patients with
      symptomatic Rathke's cleft cysts are discussed. Eight patients were treated by
      the authors and 147 were collected in a review of the literature. This lesion
      occurred more often in female than male patients by a 2:1 margin, and the mean
      age at presentation was 38 years. The average patient had been symptomatic for
      nearly 3 years at the time of treatment, with the most common symptoms and signs
      being pituitary dysfunction, visual disturbances, and headaches. Affected
      children generally were pituitary dwarfs. The sella was enlarged in 80% of cases,
      and the cyst was situated in both an intrasellar and a suprasellar location in
      71%. Computerized tomography revealed a low-density cystic mass with capsular
      enhancement in one-half of the cases. A variable appearance was seen with
      magnetic resonance imaging. Partial excision and drainage of the cyst by the
      transsphenoidal approach is the recommended treatment, as the recurrence rate is
      low. Most symptoms and signs improved or resolved following surgery with the
      exception of hypopituitarism and diabetes insipidus. The cyst lining was usually
      composed of ciliated cuboidal or columnar epithelium. Theories as to the origin
      of Rathke's cleft cysts are also discussed.

PMID- 2002367
TI  - Stereotactic radiosurgery of meningiomas.
AB  - Stereotactic radiosurgery has an expanding role in the management of selected
      intracranial tumors. In an initial 30-month experience using the 201-source
      cobalt-60 gamma knife at the University of Pittsburgh, 50 patients with
      meningiomas were treated. The most frequent site of origin was the skull base.
      Previously, 36 patients (72%) had undergone at least one craniotomy and four
      patients (8%) had received fractionated external beam radiation therapy.
      Stereotactic radiosurgery was the primary treatment modality in 16 patients (32%)
      with symptomatic tumors demonstrated by neuroimaging. Computer imaging-generated
      isodose plans (with one to five irradiation isocenters) for single-treatment
      irradiation gave optimal (greater than or equal to 50% isodose line) coverage in
      44 patients (88%). The proximity of cranial nerves or vascular, pituitary, and
      brain-stem structures to the often convoluted tumor mass was crucial to dose
      selection. Serial imaging studies were evaluated in all 50 patients. Twenty-four
      patients were examined between 12 and 36 months after treatment; 13 (54%) showed
      a reduction in tumor volume while nine (38%) showed no change. Of 26 patients
      evaluated between 6 and 12 months after treatment, four showed a decrease in
      tumor size while 22 showed no change. Two patients (both with large tumors that
      received suboptimal irradiation) had delayed tumor growth outside the
      radiosurgical treatment volume. The actuarial 2-year tumor growth control rate
      was 96%. Between 3 and 12 months after radiosurgery, three patients developed
      delayed neurological deficits that gradually improved, compatible with delayed
      radiation injury. Although extended follow-up monitoring over many years will be
      necessary to fully evaluate treatment, to date stereotactic radiosurgery has
      proved to be a relatively safe and effective therapy for selected patients with
      symptomatic meningiomas, including those who failed surgical resection.
      Radiosurgery was an effective primary treatment alternative for those patients
      whose advanced age, medical condition, or high-risk tumor location mitigated
      against surgical resection.

PMID- 2002368
TI  - Language function following anterior temporal lobectomy.
AB  - The authors report the results of a prospective investigation that evaluated
      postoperative changes in language function after dominant (29 cases) or
      nondominant (35 cases) anterior temporal lobectomy for treatment of complex
      partial seizures. These patients received conservative resection of lateral
      temporal cortex but aggressive resection of medial temporal cortex. None of the
      patients underwent functional mapping of cortical language ability. All patients
      were assessed with a standardized aphasia battery (Multilingual Aphasia
      Examination) before and 6 months after surgery. Postoperatively, the dominant
      anterior temporal lobectomy group did not show any significant losses in language
      function compared to patients who underwent nondominant anterior temporal
      lobectomy. In addition, the dominant temporal lobectomy group showed significant
      postoperative improvement in complex receptive language comprehension compared to
      the nondominant group. These results suggest that patients with complex partial
      seizures of medial temporal lobe onset can undergo a conservative resection of
      lateral temporal cortex without language mapping. Such surgery carries little
      risk to language function and provides an excellent postoperative surgical
      outcome.

PMID- 2002369
TI  - Giant carotid-ophthalmic artery aneurysms: direct clipping utilizing the
      "trapping-evacuation" technique.
AB  - The authors have devised a "trapping-evacuation" technique to facilitate direct
      clipping of giant aneurysms in the paraophthalmic region of the internal carotid
      artery (ICA). The giant aneurysm is collapsed by first trapping the aneurysm by
      temporary occlusion of the cervical common carotid and external carotid arteries,
      along with temporary clipping of the intracranial ICA distal to the aneurysm.
      Thereafter, intra-aneurysmal blood is simultaneously aspirated through a catheter
      placed in the cervical ICA. Exposure of the proximal end of the aneurysm neck is
      mandatory for successful clipping. This is accomplished by extensive unroofing of
      the optic canal, removal of the anterior clinoid process, opening of the anterior
      part of the cavernous sinus, and exposure of the most proximal intradural (C2)
      and genu (C3) portions of the ICA. Four cases of giant aneurysms of the
      paraophthalmic ICA were successfully treated by this technique and the
      postoperative outcome was good in all cases. Preoperative magnetic resonance
      imaging for evaluation of the anatomical details, balloon occlusion test of the
      ICA, and intraoperative measurement of cortical blood flow were important to the
      success of the operation. Intraoperative digital subtraction angiography via the
      catheter placed in the cervical ICA was useful in confirming successful clipping.

PMID- 2002370
TI  - Seizure outcome from anterior and complete corpus callosotomy.
AB  - Eighty patients underwent anterior corpus callosotomy for treatment of
      generalized seizures. The patients' mean age was 18.3 years (range 4 to 53
      years); the mean age at seizure onset was 5.27 years (range 0.1 to 27 years). The
      mean intelligence quotient (IQ) of 41 testable patients was 71.12 (range less
      than 30 to 114). The seizure outcome was as follows: 13% were seizure-free, 65%
      were significantly improved, and 22% were unchanged. Ten patients subsequently
      underwent a second operation to complete the callosal sectioning which resulted
      in additional seizure improvement in only five of them. Five complications
      resulted from 90 operations: two epidural hematomas, one delayed subdural
      hematoma, one bone-flap infection, and one postcallosotomy disconnection
      syndrome; two patients died. A younger age at onset of seizures, a higher IQ, and
      generalized tonic-clonic, atonic, complex-partial, and mixed seizure types were
      associated with improved seizure outcome.

PMID- 2002371
TI  - Sequential magnetic resonance imaging following stereotactic radiofrequency
      ventralis lateralis thalamotomy.
AB  - Serial postoperative magnetic resonance (MR) studies were obtained in 21 patients
      who underwent somatotopically placed stereotactic radiofrequency (rf) ventralis
      lateralis thalamotomy for the control of movement disorders. The MR studies were
      reviewed to determine the MR characteristics of early-phase (less than or equal
      to 7 days) and late-phase (8 days to 5 months) lesions. Surgery was performed for
      the control of parkinsonian tremor (14 cases), intention tremor (six cases), and
      essential tremor (one case). Single rf lesions were made with an electrode (1.6
      mm in diameter, 3 mm in tip length) heated to 78 degrees C for 60 seconds. On MR
      images of the lesions, three distinct concentric zones were identified, described
      as follows (from the center outward). Zone 1 gives increased signal on long
      relaxation time (TR) (T2-weighted) MR images in early- and late-phase lesions and
      decreased signal on short-TR (T1-weighted) MR images in early-phase lesions only.
      Zone 2 gives decreased signal on long-TR (T2-weighted) images in early- and late
      phase lesions; it gives isointense signal on short-TR (T1-weighted) images in
      early-phase lesions only. Zone 3 gives increased signal on long-TR (T2-weighted)
      images in early-phase lesions only and decreased signal on short-TR (T1-weighted)
      MR images in early-phase lesions only. It is considered that in early-phase
      lesions, Zone 2, with a mean diameter of 7.3 mm on axial long-TR (T2-weighted)
      imaging, represents an area of hemorrhagic coagulation necrosis. In late-phase
      lesions, Zone 2, with a mean diameter of 5.0 mm on axial long-TR (T2-weighted)
      imaging, represents hemosiderin deposition. Zone 3 likely represents edema, and
      this zone disappears between the early and late periods. From regression
      analysis, lesion size began to stabilize at approximately 7 months with a mature
      lesion diameter of 3.3 mm. Long-term follow-up monitoring (median 16 months)
      showed good tremor control. Based on clinical and radiological findings, the
      authors conclude that forms of hemoglobin are suitable markers to assess the size
      of rf lesions. Serial MR imaging provides a noninvasive means of studying the
      evolution of rf thalamotomy lesions.

PMID- 2002372
TI  - Familial occurrence of arteriovenous malformation of the brain.
AB  - Brain arteriovenous malformations are considered to originate from a congenital
      maldevelopment of the brain vessels. Although there have been occasional reports
      suggesting a familial incidence of these lesions, data for only 10 families have
      been accumulated in the literature. The authors report on six such cases in three
      families. This high rate of occurrence of familial cases suggests an involvement
      of genetic factors.

PMID- 2002373
TI  - Intracranial pressure and cerebrospinal fluid outflow conductance in healthy
      subjects.
AB  - Conductance of cerebrospinal fluid (CSF) outflow (Cout) is an important parameter
      to be considered in patients with CSF circulation abnormalities. In patients with
      normal-pressure hydrocephalus it is the single most important parameter in
      determining if the patient needs CSF shunting. The lower normal limit for Cout
      has been estimated from the effect of shunting in patients with normal-pressure
      hydrocephalus, from patients retrospectively reevaluated after recovering from
      illness, and from patients with known abnormalities in the brain or the CSF
      system. The true value of Cout in normal individuals, however, has hitherto not
      been reported. In the present study, Cout has been measured by a lumbar infusion
      test in eight young volunteers with no suspicion of disease. The mean
      intracranial pressure (ICP) was 11 mm Hg and a linear relationship was found
      between CSF absorption and ICP. The mean Cout was 0.11 ml/min/mm Hg and the lower
      95% confidence level was 0.10 ml/min/mm Hg. These values are in accordance with
      those obtained from previous studies.

PMID- 2002374
TI  - Subarachnoid hemorrhage of unknown etiology: early prognostic factors for long
      term functional capacity.
AB  - Forty-one patients suffering subarachnoid hemorrhage (SAH) of unknown etiology
      were re-investigated at an average of 91 months after the bleed to determine
      functional capacity. Nineteen patients were performing at their previous level of
      work, five were employed part-time, and four could not work due to the SAH. Five
      patients showed a moderate disability in activities of daily living but were not
      dependent on help, one patient was severely disabled, and two had died. There was
      one rebleed. Early prognosis of an unfavorable outcome was possible on the basis
      of three clinical variables on admission: a history of hypertension, a Hunt and
      Hess grade of greater than II, and the presence of focal neurological deficits.
      In addition, the presence of an organic mental syndrome at discharge was
      identified as a predictive factor for reduced functional capacity later on. Other
      clinical variables in the acute stage, including sex, age, history of headache,
      interval between SAH and admission, impaired consciousness, and cognitive
      deficits, were not related to a limited functional level. Residual neurological
      deficits and the Glasgow Outcome Scale score on discharge were also not
      predictive of restrictions in global functions evaluated by means of the
      Karnofsky Performance Scale status at follow-up review.

PMID- 2002375
TI  - Gangliosides: the relevance of current research to neurosurgery.
AB  - Gangliosides are complex glycolipids found on the outer surface of most cell
      membranes: they are particularly concentrated in tissues of the nervous system.
      Gangliosides form part of the immunological identity of mammalian cells and are
      involved in a variety of cell-surface phenomena such as cell-substrate binding
      and receptor functions. In tumorous tissue, the ganglioside composition is
      altered, sometimes in direct proportion to the degree of malignancy. The
      literature on the glycosphingolipid composition and immunology of intracranial
      tumors is reviewed. Some gangliosides induce neuritogenesis and exhibit a trophic
      effect on nerve cells grown in vitro. In vivo, a particular ganglioside, GM1,
      reduces cerebral edema and accelerates recovery from injury (traumatic and
      ischemic) to the peripheral and central nervous systems of laboratory animals.
      Preliminary clinical studies have shown that treatment with gangliosides may have
      corresponding effects on lesions of the human peripheral nervous system.
      Gangliosides have not been tested in human subjects with brain injury.

PMID- 2002376
TI  - A histological and flow cytometric study of dog brain endothelial cell injuries
      in delayed radiation necrosis.
AB  - The pathogenesis of delayed cerebral radiation necrosis was studied
      histologically and biochemically in 25 dogs with special attention to vascular
      endothelial cell injuries. The dogs were sacrificed 3 to 30 months after
      irradiation with a single dose of 15 Gy to the head. Brain specimens were
      appropriately fixed for light and electron microscopic studies, and capillary
      endothelial cells were isolated for flow cytometric study. The endothelial cells
      were stained with acridine orange, then the cell ratios in the reproductive phase
      (S + G2 + M) were investigated with flow cytometry. Thereafter, Feulgen
      hydrolysis and computer analysis of the hydrolysis curves were performed to
      examine the qualitative changes in deoxyribonucleic acid (DNA) of endothelial
      cells after irradiation. Under light microscopy, spongy degeneration with small
      cell infiltration was observed, especially in the frontal white matter, at 6
      months after irradiation. At 9 months, necrotic foci appeared and developed until
      15 months after irradiation. Blood vessels around the necrotic area showed
      luminal narrowing with endothelial hyperplasia and proliferation. At 30 months,
      no fresh necrotic lesions were observed. Under electron microscopy, endothelial
      cells of capillaries and small vessels around the necrotic area showed an
      increase of pinocytosis, and in the nuclei there was an increase of infoldings
      and euchromatin. The cell ratios in the reproductive phase were 14.5% to 23.3%
      (maximum at 9 months) in the irradiated group compared to 6.4% in the control
      group. The rate constant of apurinic acid production, a parameter correlating
      with DNA transcriptional activity, was minimum at 3 months and maximum at 9
      months after irradiation. The data suggest that impairment of the
      microcirculation plays an important role in the pathogenesis of delayed radiation
      necrosis, and that the time of necrosis occurrence closely correlates with the
      cell cycle of vascular endothelial cells.

PMID- 2002377
TI  - Lack of neural control and reactivity to vasoactive agents in malignant glioma
      arteries.
AB  - Vessels in malignant brain tumors have a defective blood-brain barrier. It is
      important to know if tumor vessels respond to vasoactive agents, since systemic
      administration of vasodilatory agents together with chemotherapy could increase
      the access of these drugs to the tumor. It was found that arteries in human
      malignant gliomas have no neural control and are totally nonreactive to various
      vasoactive agents. The vessels lose their reactivity within 1 to 2 mm outside the
      visible tumor front.

PMID- 2002378
TI  - Histological assessment of nerve lesions caused by epineurial electrode
      application in rat sciatic nerve.
AB  - The left sciatic nerve of 36 rats was exposed and four ring-shaped stainless
      steel wire electrodes were sutured to the epineurium of each nerve in the same
      manner as performed clinically for "carousel stimulation" in man. The rats were
      sacrificed 10 days (Group 1), 3 weeks (Group 2), or 3 months (Group 3) after
      implantation. The electrodes were excised, the nerves were embedded in Epon, and
      semithin sections were obtained for histological and planimetric assessment of
      lesions caused by the epineurially sutured electrodes. The right sciatic nerves
      served as controls. The total area of neural tissue within the perineurium was
      determined at three levels: at the site of the electrodes, 8 mm proximal, and 8
      mm distal. The area of neural tissue damaged by the surgical procedure was
      expressed as a percentage of the total area. In Group 1, nine of 12 nerves showed
      lesions ranging from 0.39% to 25.39% of the total area of neural tissue, in Group
      2 eight of 11 sciatic nerves showed lesions ranging from 0.24% to 13.03% of the
      total area, and in Group 3 five of 12 nerves showed lesions ranging from 0.21% to
      4.96% of the total area. The pathologically altered areas in Groups 2 and 3
      exhibited distinct signs of nerve fiber regeneration. The reasons for the
      decrease in damage from Group 1 to Group 3 and the clinical implications of the
      results for long-term electrical stimulation are discussed.

PMID- 2002379
TI  - In vivo incorporation of [9,10(-3)H]-palmitate into a rat metastatic brain-tumor
      model.
AB  - Lipid metabolism of an intracerebrally implanted brain tumor and normal brain was
      investigated in awake Fischer 344 rats using intravenously injected [9,10(-3)H]
      palmitate as a probe. A suspension of Walker 256 carcinosarcoma cells (250 cells
      in 5 microliters medium), with or without 1% low-melting-point agar, was
      implanted into the caudate nucleus of rats 8 to 9 weeks old. Control animals
      received an intracerebral injection without tumor cells. Seven days after
      implantation, awake rats were infused intravenously for 5 minutes with [9,10(
      3)H]-palmitate (6.4 mCi/kg). The rats were killed 20 minutes after initiation of
      the infusion and coronal brain slices were obtained for quantitative
      autoradiography and light histological study. Tumor cell masses were
      histologically well demarcated from the surrounding brain tissue. Tumor tissue
      incorporation of [9,10(-3)H]-palmitate was heterogeneous, ranging on average from
      3.1- to 6.1-fold greater than in the corresponding contralateral brain. In
      addition, incorporation corresponded to regional tumor cell density. The
      incorporation rate constant of [9,10(-3)H]-palmitate in tumor was significantly
      increased compared to control brain and was independent of tumor size. Necrotic
      areas within tumors showed no incorporation of radiolabeled palmitate. Brain
      surrounding the tumors and control injection sites showed reactive gliosis, and
      possessed 30% greater incorporation of [9,10(-3)H]-palmitate than contralateral
      normal brain. These results suggest that [9,10(-3)H]-palmitate can be used to
      image brain tumors in vivo, measuring turnover and/or synthesis of tumor and
      brain lipid.

PMID- 2002381
TI  - Postoperative ectopic craniopharyngioma. Case report.
AB  - The case of an ectopic craniopharyngioma arising from a seed of tissue deposited
      along the operative track is reported. The uniqueness of this lesion is
      addressed. Ideal therapy and controversies regarding radiation therapy of
      craniopharyngiomas are discussed in light of this new variation in recurrence.

PMID- 2002380
TI  - Hemifacial spasm caused by a spontaneous dissecting aneurysm of the vertebral
      artery. Case report.
AB  - The authors describe the first reported case of dissecting aneurysm presenting
      with hemifacial spasm. The patient was a 58-year-old woman with left hemifacial
      spasm of 2 years' duration. Cranial nerve examination was otherwise normal and no
      other clinical symptoms were observed. Vertebral angiography revealed a fusiform
      enlargement of the left vertebral artery and contrast medium remaining in the
      intramural false lumen in the venous phase. Microvascular decompression of the
      facial nerve with wrapping of the aneurysm resulted in complete relief of the
      hemifacial spasm.

PMID- 2002382
TI  - Shunt nephritis. Case report.
AB  - The incidence of shunt nephritis has decreased over the past several years due to
      the increased use of ventriculoperitoneal (VP) shunts rather than the
      ventriculovascular systems for which this complication was originally reported in
      1965. Despite this trend, the syndrome has been reported in cases of VP shunting
      and, for this reason, merit a renewed look. Shunt nephritis is thought to be
      secondary to immune complex formation and deposition in the kidney in response to
      Staphylococcus epidermidis. The diagnostic workup and management of this disease
      is discussed.

PMID- 2002383
TI  - Magnetoencephalographic localization of interictal spike sources. Case report.
AB  - The reliability of localization of interictal spike sources using
      magnetoencephalography (MEG) was examined by repeated measurements in a patient
      with temporal lobe epilepsy. During two preoperative recording sessions, the
      estimated sources, projected onto magnetic resonance images of the patient's
      brain, were found to lie less than 1 cm apart within the area subsequently
      resected. The MEG localization was in close agreement with intraoperative
      cortical recordings.

PMID- 2002384
TI  - Vertical odontoid fracture. Case report.
AB  - A case of vertical odontoid fracture is presented in which a concomitant fracture
      of the skull indicated possible pathogenetic mechanisms. The radiological
      diagnosis and the management of this case are discussed.

PMID- 2002385
TI  - Primary central nervous system T-cell lymphoma. Case report.
AB  - Primary central nervous system (CNS) T-cell lymphoma is extremely rare. The
      present case report provides immunocytochemical evidence for a cerebellar CNS T
      cell lymphoma. The patient underwent surgery followed by radiation therapy and is
      alive and well 36 months postoperatively. The clinical and pathological features
      of primary CNS T-cell lymphoma as well as diagnostic measures and treatment
      options are discussed, together with a compilation of all previous case reports
      of primary CNS T-cell lymphomas.

PMID- 2002386
TI  - Optimal wound closure after tethered cord correction. Technical note.
AB  - A technique of wound closure following tethered cord correction is presented that
      significantly reduces the incidence of cerebrospinal fluid collections in the
      subcutaneous space. In over 60 cases, the described method of fascia and skin
      closure has lessened wound problems to a minimal level. Patient hospitalization
      time has also been greatly diminished.

PMID- 2002387
TI  - Intraoperative protection of cranial nerves and perforating arteries by silicone
      rubber sheets. Technical note.
AB  - The authors describe a technique whereby, during microneurosurgery, vital
      structures are covered or wrapped with small pieces of silicone rubber sheeting
      to protect them from intraoperative injury. In this way, perforating arteries
      located behind a large aneurysm can be covered to avoid their inclusion within
      the blades of the clip, and the cranial nerves coursing around or through a tumor
      can be wrapped to protect them from injury by a suction or forceps. By insulating
      nerves and arteries, this silicone rubber sheet has the added advantage of
      protecting them from injury due to electrical current of bipolar forceps. The
      silicone rubber sheet described here is smoother, thinner, and lighter than a
      cotton pattie.

PMID- 2002388
TI  - Glioma growth and the protein kinase-C system.

PMID- 2002389
TI  - Hearing loss from petrous-to-supraclinoid carotid bypass.

PMID- 2002390
TI  - Valsalva maneuver or Pare maneuver?

PMID- 2002391
TI  - JNM home-study programs. Quality, affordable CEUs at your fingertips.

PMID- 2002392
TI  - Psychosexual changes associated with the perimenopausal period.
AB  - The perimenopausal period is often a frustrating time for the woman who is
      experiencing it and for the health care professional who provides care for her.
      Although menopause is a universal experience for women, how it is experienced is
      not universal. Physiology, anatomy, social support systems, culture,
      expectations, and the woman's attitudes (especially her self-image) all have an
      influence on how easy or difficult the perimenopausal transition period is for an
      individual. This paper discusses psychosexual aspects of the perimenopausal
      period and suggests how nurse-midwives or other health professionals can make
      this often difficult period easier.

PMID- 2002393
TI  - A theoretical model of the perimenopausal process.
AB  - The purpose of this qualitative investigation was to generate theory grounded in
      the responses of perimenopausal women about the process of menopause. A purposive
      sample of 12 perimenopausal women was interviewed to discover the menopausal
      process. Data were generated from interviews, two-month daily logs, and field
      notes. A substantive theory of Integrating a Changing Me identified the
      perimenopausal process, which included four categories: Tuning Into Me, My Body
      and Moods, which described the awareness of physical and emotional changes that
      initiated the beginnings of menopause; Facing a Paradox of Feelings, which
      reflected the thoughts, perceptions, and feelings experienced by perimenopausal
      women. Contrasting Impressions, which described the assimilation of information
      and the formulation of the woman's own personal meaning; and Making Adjustments,
      which included changes made by the women in response to this process.
      Implications for health care and education of perimenopausal women are discussed.

PMID- 2002394
TI  - Perimenopausal hormone replacement therapy. Review of the literature.
AB  - Hormonal replacement therapy--usually involving estrogen with or without an added
      progestin--has been proposed as a treatment for a variety of changes associated
      with the perimenopausal years, including hot flushes, vaginal and urinary tract
      atrophy, sexual problems, aging skin, and a number of affective symptoms. It has
      also been studied as a preventive measure against osteoporosis and cardiovascular
      disease, with some researchers claiming a protective effect against breast
      cancer, although others cite it as a risk factor for breast cancer. This article
      reviews the literature in each of these areas, suggesting an individualized
      approach to hormone replacement therapy, determined by patient and practitioner,
      based on symptomatology and risk factors. Alternative therapies are briefly
      outlined.

PMID- 2002395
TI  - Dysfunctional uterine bleeding and amenorrhea. Differential diagnosis and
      management.
AB  - The differential diagnosis and clinical management of abnormal uterine bleeding
      and of amenorrhea present complex challenges to the provider of well woman
      gynecologic care. The physiologic origins of these problems are detailed and
      related to historical information, possible physical findings, and laboratory
      test results. In particular, dysfunctional uterine bleeding is distinguished from
      other causes of bleeding such as infections, carcinoma, ectopic pregnancy, side
      effects of contraception, and benign disorders such as myomas. The differential
      diagnosis of amenorrhea is also presented with attention to medical and exogenous
      causes, as well as amenorrhea due to alterations of hypothalamic function;
      pituitary, ovarian, thyroid, and adrenal dysfunction; and abnormalities of the
      outflow tract. Strategies are presented for initiating the clinical investigation
      of these problems, when to comanage with a gynecologist, and when to refer.

PMID- 2002396
TI  - Breast disease. The role of the nurse-midwife.
AB  - Certified nurse-midwives provide primary care for women. An essential part of a
      physical examination is a complete assessment of the breasts. Normal breasts and
      their variations and deviations are discussed, with particular attention paid to
      breast pain, masses, and nipple discharge, and the clinical implications of each.
      In addition, the demographics, risk factors, staging criteria, and treatment
      modalities of breast cancer are presented.

PMID- 2002397
TI  - Delay in diagnosis of breast cancer. A professional liability risk.
AB  - This article notes that liability claims of failure to diagnose breast cancer are
      increasing in number and severity, at least in part because women understand that
      early diagnosis improves survival. Legal cases are presented that illustrate
      particular liability risks, and risk management recommendations are made.

PMID- 2002398
TI  - The perimenopausal period. Implications for nurse-midwifery practice.
AB  - As more women move into their 40s, it can be anticipated that nurse-midwives will
      be sought to continue to provide care and anticipatory guidance in the
      perimenopausal period. This article reviews definitions, demographics,
      physiology, and clinical manifestations of the perimenopausal period. In
      addition, management strategies other than hormone replacement therapy for the
      common discomforts of menopause are identified and discussed.

PMID- 2002399
TI  - The importance of alpha-lactalbumin in infant nutrition.
AB  - The ideal "humanization" of milk substitutes should include the creation of an
      amino acid pattern closely resembling that of human milk. Because the mixture of
      proteins in human milk is particularly rich in tryptophan and cysteine and low in
      methionine, this pattern is difficult to achieve with commercially available
      proteins. Even whey-predominant formulas only approximate human milk. Human milk
      has a high concentration of whey protein (70% of total protein). Of this, alpha
      lactalbumin, a component of the lactase synthetase complex, accounts for 41% of
      the whey and 28% of the total protein. Only 3% of the protein in bovine milk is
      alpha-lactalbumin. Human and bovine alpha-lactalbumin share a 72% amino acid
      sequence homology. Both proteins contain (wt/wt) 6% tryptophan and 5% cysteine
      but only 0.9% methionine. Thus the differences in the amino acid compositions of
      bovine and human milks are largely attributable to differences in their alpha
      lactalbumin contents. Commercial availability of bovine alpha-lactalbumin would
      allow the construction of infant formulas with amino acid compositions that are
      very close to that of human milk. alpha-Lactalbumin would also be a valuable
      constituent of diets for patients whose protein intake must be restricted.

PMID- 2002400
TI  - Effects of dietary selenium and fish oil (MaxEPA) on arachidonic acid metabolism
      and hemostatic function in rats.
AB  - This study investigated whether hemostatic function can be modified by both the
      consumption of fish oil and the level of dietary selenium. Male Sprague-Dawley
      rats were fed for 8 wk semipurified diets containing 7% corn oil (by wt) or 5.5%
      fish oil (MaxEPA) plus 1.5% corn oil with or without selenium supplementation.
      Consumption of the four diets caused no difference in weight gain, food intake or
      plasma malondialdehyde content. The selenium-supplemented rats had significantly
      higher levels of selenium and glutathione peroxidase activity in plasma. Fish oil
      feeding decreased ADP-induced platelet aggregation and increased bleeding time.
      The level of dietary selenium and type of oil interacted to influence the
      production of 6-keto-prostaglandin F1 alpha: more was produced when corn oil was
      fed in the selenium-deficient diets. These data suggest that the effect of
      dietary selenium on hemostatic function and the production of eicosanoids is
      minor.

PMID- 2002401
TI  - Leucine-induced amino acid antagonism in rats: muscle valine metabolism and
      growth impairment.
AB  - The deleterious effects of branched-chain amino acid (BCAA) antagonism caused by
      excess dietary leucine include growth depression and subnormal valine and
      isoleucine pools. To investigate mechanisms causing these changes, rats were
      gavage-fed low-protein (9%) diets with or without BCAA supplements, and the
      metabolism of another BCAA (valine) was measured in incubated rat epitrochlearis
      muscles. A 10% leucine supplement (HL-10) inhibited growth; growth remained
      subnormal even when 2.6% isoleucine and 2.4% valine (HLIV-10) were added to the
      diet. Valine decarboxylation in muscle increased 170-270% in rats fed the HL-10
      or HLIV-10 diets, but was still markedly lower than we previously found in muscle
      of rats fed a 14% protein diet. Valine incorporation into muscle protein as an
      estimate of protein synthesis was unaffected by any of the BCAA supplements. When
      a lower (4%) concentration of leucine (without or with 0.16% isoleucine and 0.16%
      valine) was studied, growth was also suppressed but only if rats had not been
      preconditioned to 9% protein. Although increased BCAA decarboxylation in muscle
      caused by excess dietary leucine contributes to low valine and isoleucine pools,
      abnormal growth appears to be independent of low valine and isoleucine levels and
      is not reflected in suppression of valine incorporation into muscle protein.

PMID- 2002402
TI  - Refeeding of rats fasted 36 hours with five different carbohydrates and with malt
      extract: differential effects on glycogen deposition in liver and muscle, on
      plasma insulin and on plasma triglyceride levels.
AB  - Rats fasted for 36 h were refed for 1, 2, 4 or 6 h with a diet containing 12
      g/100 g casein, 2 g/100 g NaCl and 86 g/100 g glucose, fructose, maltose,
      sucrose, starch or malt extract. Blood glucose reached constant levels after 1 to
      2 h of refeeding. The increase in plasma insulin paralleled food intake rather
      than the increase in blood glucose. Plasma triglycerides decreased upon refeeding
      starch, maltose and malt extract and increased with sucrose and fructose.
      Recovery of absorbed carbohydrates was highest in rats refed malt extract.
      Glycogen deposition in muscle was highest in rats fed malt extract and lowest in
      those fed fructose; sucrose yielded intermediate values. Glucose, maltose and
      starch resulted in muscle glycogen depositions slightly lower than those obtained
      with malt extract. In liver, sucrose and fructose were better precursors for
      glycogen than glucose and starch. With carbohydrates containing only glucose
      units, much more glycogen was found to be deposited in total muscle than in
      liver. This asymmetry was less notable or even was reversed with sucrose and
      fructose. Glycogen deposition in muscle and in liver is influenced by the
      carbohydrate used for refeeding, and muscle, rather than liver, is the main
      glycogen storing tissue.

PMID- 2002403
TI  - Fermentable carbohydrate reaching the colon after ingestion of oats in humans.
AB  - A simulated digestion technique was used to investigate the characteristics of
      starch hydrolysis in uncooked, cooked and extrusion-cooked oat products in vitro.
      The rate and extent of starch hydrolysis were both significantly lower in
      uncooked rolled oats than in the same material after brief boiling or extrusion
      cooking. A similar degree of maldigestion in vivo would lead to as much as an
      estimated 68% of oat starch entering the colon. Breath-hydrogen measurements were
      used to compare the fermentable carbohydrate content of uncooked and briefly
      boiled rolled oats in human volunteers and to estimate the relative contributions
      of soluble dietary fiber and undigested starch to the fermented component.
      Isolated oat gum (beta-glucan) was readily fermented in vivo and was apparently
      the main fermentable component of cooked rolled oats. Uncooked rolled oats gave a
      higher excess hydrogen production than cooked oats, but the results were variable
      and the differences not statistically significant. In an additional experiment,
      lactulose was used as a fermentable reference material to calculate the apparent
      fermentable carbohydrate content of rolled oats and oat gum. Uncooked rolled oats
      were estimated to contain a statistically significant quantity of undigested
      starch, amounting at most to 1.01 +/- 0.40 g (mean +/- SEM) of undigested starch
      per 50 g of fresh weight. We concluded that starch hydrolysis in oats is limited
      to some extent by the physical state of the food matrix, but this effect may be
      greatly overestimated by simulated digestion procedures in vitro.

PMID- 2002404
TI  - Influence of age and sex on vitamin B-6 vitamer distribution and on vitamin B-6
      metabolizing enzymes in Wistar rats.
AB  - Vitamin B-6 vitamer distribution and activities of vitamin B-6 metabolizing
      enzymes were evaluated in aging male and female Wistar rats fed a purified diet
      (containing 250 g of casein and 6 mg of pyridoxine hydrochloride per kg) from
      weaning until 31 mo of age. Plasma pyridoxal 5'-phosphate (PLP) concentration
      became lower with increasing age, with the largest decrease in the 1st yr of
      life. An age-related change in vitamin B-6 distribution between the various
      tissues examined was observed: B-6 vitamer content increased in heart and brain,
      whereas PLP content decreased in gastrocnemius muscle, kidney and liver. The
      decrease in muscle PLP content occurred in concert with a decrease in muscle
      glycogen phosphorylase activity. Urinary 4-pyridoxic acid (4-PA) excretion
      increased with age, especially in female rats, in parallel with an increase in
      liver pyridoxal oxidase and pyridoxal dehydrogenase activities. Age-related
      changes in vitamin B-6 distribution were probably not causally related to changes
      in activity of vitamin B-6 metabolizing enzymes; they were regarded as
      consequences of changes in protein metabolism. The higher urinary 4-PA excretion
      in older rats may reflect a lower vitamin B-6 requirement; however, the lower PLP
      content of gastrocnemius muscle may indicate an age-related decrease in vitamin B
      6 body stores.

PMID- 2002405
TI  - Blood pressure, fluid compartments and utilization of chloride in rats fed
      various chloride diets.
AB  - The effects of various levels and types of dietary chloride salts on blood
      pressure were examined in three studies. Weanling Sprague-Dawley rats were fed
      semipurified diets that contained moderate (1.9 mg Cl/g diet) and supplemental
      (15.6 mg Cl/g diet) chloride as NaCl, KCl, lysine monohydrochloride with or
      without CaCO3, or MgCl2 for 56 or 119 d. Rats fed excess chloride excreted more
      than 84% of the chloride in urine, excreted increased urine volumes (from 3 to 7
      wk), tended to consume more fluids (especially if NaCl was fed), had
      significantly increased blood pressure (7 and 13 wk), had hypertrophied kidneys
      (8 and 17 wk) and had altered levels of sodium and potassium in their kidneys (17
      wk), but experienced no changes in the size of fluid compartments, such as plasma
      volume or bromine space. Altogether, 56% of the variance in blood pressure
      measurements at wk 7 could be predicted on the basis of urinary chloride
      excretion during wk 7 and kidney weight as a percentage of body weight and kidney
      sodium concentration, but only 30% of the variance in blood pressure measurements
      at wk 16 could be predicted on the basis of urinary chloride excretion during wk
      16 and kidney sodium concentrations.

PMID- 2002406
TI  - The influence of zinc-binding ligands in fetal circulation on zinc clearance
      across the in situ perfused guinea pig placenta.
AB  - Although zinc is essential for normal fetal growth and development, little is
      known about factors that influence its transfer across the placenta. The in situ
      perfused guinea pig placenta model was used to study the influence of zinc
      binding ligands in fetal circulation on maternofetal placental zinc transfer. A
      placenta of each anesthetized sow was perfused (on the fetal side) with a
      physiological perfusate via the umbilical vessels, with the fetus excluded. The
      sow was infused intravenously with 65Zn as a tracer of placental zinc clearance
      and with antipyrine as an indirect indicator of maternal placental blood flow.
      Maternal plasma and placental effluent samples collected at intervals were
      counted for 65Zn with a gamma counter, and the absorbance of nitrosated
      antipyrine was measured at 350 nm. The addition of physiological levels of zinc
      binding ligands (albumin, L-histidine and L-cysteine) to the perfusate increased
      the relative maternofetal clearance of zinc across the placenta calculated as
      zinc clearance/antipyrine clearance [mean +/- SEM; 0.113 +/- 0.016 vs. 0.062 +/-
      0.012; ligands vs. no ligands; n = 8; P less than 0.05]. The results suggest that
      the availability of zinc-binding ligands in fetal circulation is one determinant
      factor of placental zinc transfer.

PMID- 2002407
TI  - Correlation between the size of the selenite-exchangeable metabolic pool and
      total body or liver selenium in rats.
AB  - This study explored the quantitative relationship between the size of the
      selenite-exchangeable metabolic pool (WSe-EMP) and total body or liver Se in rats
      of varying age and past Se intake. We performed four experiments. In one,
      weanling rats were fed either a Se-deficient or Se-supplemented diet for 30 d,
      followed by measurement of WSe-EMP and total body Se. For the other experiments,
      rats were fed natural sources of Se without added selenite until adult age and
      then either subjected to acute Se restriction during the 7 d of measurements or
      maintained on a Se-sufficient diet. For the animals fed the selenite diet, the 7
      d average ratio of WSe-EMP:total body Se (Se(end),0) was 0.370 +/- 0.009, which
      was not significantly different from the corresponding value (0.350 +/- 0.018, P
      greater than 0.05) for the Se-deficient group. When the group mean values of WSe
      EMP were correlated with the corresponding mean values of Se(end),0 for all
      experiments, we obtained highly linear relations (r2 greater than 0.96). When WSe
      EMP for each animal was correlated with the corresponding value of total body
      endogenous Se (Se(end)) or liver Se(end) (for t = 1 or 7 d), we found equally
      strong linear relations (r2 greater than or equal to 0.99). We concluded that WSe
      EMP accurately reflected total body Se content or the Se content of such organs
      as liver, regardless of past Se intake, chemical form of Se or age and size of
      the animals.

PMID- 2002408
TI  - Branched-chain and other amino acids in tissues of rats fed leucine-limiting
      amino acid diets containing norleucine.
AB  - Amino acid concentrations were measured in plasma, brain, muscle and liver from
      rats fed leucine-limiting diets containing varying proportions of other
      indispensable amino acids (IAA), the branched-chain amino acids (BCAA) and
      norleucine, a BCAA analog known to compete with large neutral amino acids (LNAA)
      for transport into tissues. Leucine was low and other IAA were high when dietary
      IAA were 125% and leucine was 65% of requirements; higher leucine and lower IAA
      concentrations occurred when dietary IAA were 75% of requirements. Tissue leucine
      was high and isoleucine and valine were low in rats fed excess leucine.
      Norleucine induced dose-dependent reductions in BCAA, especially in brain and
      muscle in which isoleucine or valine were sometimes undetectable. Leucine was not
      depressed further when control values were low as in the rats fed 125% IAA.
      Norleucine frequently prevented the high BCAA found after feeding additional
      BCAA. Other LNAA tended to be low in the brain and muscle of rats fed norleucine.
      Lysine was high only in the tissues of rats fed 75% IAA and norleucine; this
      effect was prevented when added leucine was given. Brain tryptophan, but not
      always serotonin, was low in rats fed norleucine. The results show transport
      related, selective and usually marked depletions of tissue BCAA in rats fed
      norleucine; this suggests norleucine may be an aid in the treatment of clinical
      conditions involving excesses of BCAA.

PMID- 2002409
TI  - Opposite effect of cold on energetic efficiency in normal and obese Wistar rats
      with hypothalamic lesions.
AB  - Reduced thermogenesis in brown adipose tissue (BAT) may contribute to increased
      energetic efficiency and obesity in rats with ventromedial hypothalamic (VMH)
      lesions. Thermogenic activity of BAT is a function of the environmental
      temperature. If a relationship exists, it follows that the increased energetic
      efficiency of VMH-lesioned rats likewise should be governed by temperature. We
      have therefore investigated the energy balance of normal and VMH-lesioned rats
      housed at 30 degrees C and 10 degrees C. Experiments at differing feeding levels
      allowed calculation of maintenance energy requirements and the net energetic
      efficiencies of each group. VMH-lesioned rats at thermoneutrality (30 degrees C)
      accumulated more body fat at all feeding levels than did normal rats. Maintenance
      energy requirement was reduced, but the net energetic efficiency did not differ
      significantly from normal. The reduced maintenance energy requirement of lesioned
      rats persisted at 10 degrees C. Net energetic efficiency decreased in normal rats
      acclimated to cold but increased in the lesioned group. The difference was
      significant (P less than 0.05). The cold-induced increase in interscapular brown
      adipose tissue (IBAT) oxidative capacity of VMH-lesioned rats was only half that
      of normal rats. Differences in BAT thermogenesis may be the basis for the
      differing temperature effects on net energetic efficiency.

PMID- 2002410
TI  - Decreased resistance and immune response to Escherichia coli infection in chicks
      with low or high intakes of vitamin A.
AB  - The effects of vitamin A excess of insufficiency on resistance to Escherichia
      coli infection and subsequent anti-E. coli immune response were examined in
      chicks. Chicks receiving depleted (0 microgram/kg), sufficient (0.85 mg/kg) or
      excess (1000 mg/kg) levels of vitamin A in their feed were inoculated by a
      subcutaneous injection of pathogenic E. coli (1 x 10(9) and 2 x 10(9) cfu per
      chick). Susceptibility to E. coli was determined by mortality, morbidity and
      immune responses (antibody production and T lymphocyte proliferation). Excess of
      insufficient vitamin A led to increased susceptibility of chicks of E. coli
      infection; this was accompanied by depressed immune responses. Chicks receiving
      excess vitamin A were more sensitive to E. coli than vitamin A-depleted chicks.
      This was reflected in higher mortality and morbidity rates and in severely
      depressed immune responses. In contrast to chicks receiving excess vitamin A, T
      lymphocyte responses (though not antibody responses) of vitamin A-depleted chicks
      achieved levels similar to those of vitamin A-sufficient birds with a lag period
      of 6 to 10 d. Therefore, reduction in resistance to E. coli infection, resulting
      from vitamin A excess or deficiency, probably was compounded by a delayed immune
      response.

PMID- 2002412
TI  - Sampling the difficult-to-sample.
AB  - Difficult-to-sample populations are defined as rare populations or populations
      that are difficult to locate, enumerate or interview. This definition includes
      subgroups of the United States population that are at increased risk of adverse
      health effects associated with malnutrition. Examples include persons who are
      rare (pregnant women), difficult to locate (migrant farm workers), difficult to
      enumerate (homeless individuals) or difficult to interview (substance abusers).
      Probability methods to sample rare and elusive populations are reviewed briefly.
      Methods include disproportionately allocated sampling, multiplicity sampling and
      the use of multiple frames. The advantages and disadvantages of nonprobability
      sampling methods are compared using criteria typically applied to assess
      alternative probability sampling methods. The cost of data collection alone may
      prohibit consideration of probability sampling methods, but caution is urged
      before abandoning this statistically sound approach to sample selection.
      Considerations for sampling the difficult-to-sample are illustrated for one such
      population, the homeless.

PMID- 2002411
TI  - Food insecurity: a nutritional outcome or a predictor variable?
AB  - The phenomenon loosely labeled hunger in the 1980s is now being discussed as food
      security or insecurity. Food security is defined as access by all people at all
      times to enough food for an active, healthy life, and at a minimum includes the
      following: 1) the ready availability of nutritionally adequate and safe foods and
      2) the assured ability to acquire personally acceptable foods in a socially
      acceptable way. Food insecurity exists whenever food security is limited or
      uncertain. The measurement of food insecurity at the household or individual
      level involves the measurement of those quantitative, qualitative, psychological
      and social or normative constructs that are central to the experience of food
      insecurity, qualified by their involuntariness and periodicity. Risk factors for
      food insecurity include any factors that affect household resources and the
      proportion of those resources available for food acquisition. Potential
      consequences of food insecurity include hunger, malnutrition and (either directly
      or indirectly) negative effects on health and quality of life. The precise
      relationships between food insecurity and its risk factors and potential
      consequences need much more research now that there is an emerging consensus on
      the definition and measurement of food insecurity. Indicators of food security or
      insecurity are proposed as a necessary component of the core measures of the
      nutritional state of individuals, communities or nations.

PMID- 2002413
TI  - Cocaine metabolites in pre-Columbian mummy hair.
AB  - Chewing of coca leaves was an integral part of many Andean pre-Columbian
      populations. Since the cocaine metabolite benzoylecognine is entrapped in hair of
      the user, this could serve as a convenient specimen for analysis. We tested the
      scalp hair of 8 Chilean mummies with dates ranging from 2,000 BC to 1,500 AD.
      This article reports that benzoylecognine is very stable and can be found in
      mummy hair.

PMID- 2002414
TI  - Recruiting into nursing: how the physician can help.
AB  - Multiple reasons for the current nursing shortage in the state and nation are
      examined. The article describes how the University of Oklahoma College of Nursing
      has endeavored to meet this growing demand for nurses through the development of
      a number of innovative options for students pursuing a nursing career. Among the
      special features of the program which are related are advanced placement for
      associate degree, diploma, and licensed practical nurses; credit by examination
      for selected beginning nursing courses; and flexible part-time scheduling. A
      number of useful strategies are provided which physicians can use to help recruit
      qualified individuals into nursing.

PMID- 2002416
TI  - Diabetes mellitus--its economic impact.

PMID- 2002415
TI  - Leaders in medicine: Hays R. Yandell, MD.

PMID- 2002417
TI  - New technology in a new decade.

PMID- 2002418
TI  - Allele losses and onco-suppressor genes.

PMID- 2002419
TI  - Translocation (11;14): a cytogenetic anomaly associated with B-cell lymphomas of
      non-follicle centre cell lineage.
AB  - Nine patients with t(11;14) and B non-Hodgkin's lymphomas composed of small to
      intermediately sized cells with irregular nuclei are described. Immunophenotyping
      was performed on seven cases, which were M+, D- with light chain restriction,
      CD5+, CD10-, and CD20+, suggesting that they were non-follicle centre cell
      lymphomas. The translocation (11;14) (in three cases the only cytogenetic
      anomaly) was associated with rearrangement of bcl-1 in four of the five cases
      investigated. Translocation (11;14) has been described in an apparently
      heterogeneous group of low-grade lymphoid malignancies which we suggest have a
      non-follicle centre cell lineage in common. This translocation may be associated
      with these lymphomas in the same way that t(14;18) is associated with follicle
      centre cell lymphomas.

PMID- 2002420
TI  - Histopathological grading of soft tissue tumours. Prognostic significance in a
      prospective study of 278 consecutive cases.
AB  - A consecutive 10-year series of 278 soft tissue sarcomas was prospectively
      graded, using a system based on the number of mitoses and taking into account
      parameters such as cellularity, anaplasia, necrosis, and histogenetic type and
      subtype of tumour. Prognostic factors in relation to metastasis-free survival
      were studied by uni- and multivariate analysis. Fifty-seven (20.5 per cent) were
      low-grade tumours, 43 (15.5 per cent) were intermediate, and 178 (64 per cent)
      were high grade. High-grade tumours were divided into two groups; 80 (29 per
      cent) grade 3A (= 5-20 mitoses per 10 high power fields (HPF)) and 78 grade 3B
      (28 per cent) (= more than 20 mitoses/10 HPF); 10 HPF corresponds to 2.5 mm2.
      Twenty (7.2 per cent) high-grade tumours could not be further subdivided. Grading
      was found to be the prognostic factor associated with the strongest predictive
      value. Five-year survival in low-grade and intermediate tumours (95 and 86
      percent, respectively) differed significantly (P less than 0.0001) from high
      grade (50 per cent) and (p = 0.0018) between grade 3A (64 per cent) and grade 3B
      (41 per cent). Other prognostic indicators of importance in high-grade tumours
      were age, local recurrence at presentation (primary operation outside the
      Centre), and localization (superficial vs. deep).

PMID- 2002421
TI  - CD1a and S100 antigen expression in skin Langerhans cells in patients with breast
      cancer.
AB  - Langerhans cells (LCs) are dendritic, antigen-presenting cells found in the
      epidermis. This study investigates the effect of early breast cancer on the
      expression of CD1a and S100 antigens by these cells. LCs were counted and
      expressed as cells/mm of epithelial basement membrane on biopsies from the skin
      overlying the tumour and from biopsies distant from the tumour. A control study
      was performed on normal breast skin, not adjacent to a lesion, from women with
      benign breast disease. The LC count of 18 patients undergoing biopsy for benign
      breast disease indicated a mean of 26 cells/mm [95 per cent confidence interval
      (CI) 23-29] and a S100/CD1a ratio of 70 per cent. In 35 cases of early breast
      cancer, the CD1a-positive LC count in the epidermis overlying the carcinoma (mean
      26/mm; 95 per cent CI 23-29) was similar, but the count made on biopsies distant
      from the tumour (mean 21/mm; 95 per cent CI 19-23) was significantly smaller. The
      percentage ratio of S100/CD1a was 71 per cent over the carcinoma and 84 per cent
      in the distant biopsies. The changes were not associated with the presence of
      nodal metastases or the oestrogen and progesterone status of the primary tumour.
      The reduction in LC numbers provides a link between decreased monocyte function
      and the decreased skin hypersensitivity responses found in patients with breast
      cancer.

PMID- 2002422
TI  - Nucleolar organizer regions and prognosis in renal cell carcinoma.
AB  - The prognostic significance of nucleolar organizer regions (NORs) in renal cell
      carcinoma (RCC) was evaluated. NORs were quantified in a series of 182 cases of
      RCC using the silver-colloid method. The cases were staged according to Robson's
      method (48 stage I, 26 stage II, 33 stage III, 75 stage IV) and mean NOR numbers
      for each tumour were correlated with survival over a 5-year period. Localized
      tumours (stages I and II) with low NOR numbers had an almost 100 per cent 5-year
      survival. Those patients with clinical evidence of metastases at presentation
      showed a high mortality, although those with low numbers of NORs had a
      significantly increased disease-free interval. Statistical analysis using the log
      rank test indicated NORs to be a significant predictor of survival over the whole
      series (P = 0.0001) and within each of Robson's stages (P = 0.0008 stage I, P =
      0.0154 stage II, P = 0.0009 stage III, P = 0.0001 stage IV). Analysis of data
      using Cox's proportional hazard model showed mean NOR numbers to be independent
      of stage as a predictor of survival.

PMID- 2002423
TI  - The histopathology of the testis and epididymis in AIDS--a post-mortem study.
AB  - The right testis and epididymis were removed at necropsy from 31 patients who had
      died with AIDS and examined microscopically. The testes showed interstitial
      fibrosis in 22 cases, thickening of seminiferous tubule basement membranes in an
      overlapping 21, and varying degrees of maturation impairment in all. Arrest of
      spermatogenesis usually occurred at the spermatocyte or spermatid stage. Five
      epididymides showed an obstructive picture, two with an associated epididymal
      cytomegalovirus infection. We discuss the possible pathogenesis of the changes in
      the HIV-infected male genital system and briefly comment on the clinical
      implications of our findings.

PMID- 2002424
TI  - NB84: a new monoclonal antibody for the recognition of neuroblastoma in routinely
      processed material.
AB  - A new monoclonal antibody NB84 recognizing an uncharacterized molecule of 57 kD
      was produced using human neuroblastoma tumour tissue as a source of antigen. The
      antibody was selected for its ability to give reliable staining on conventional
      formalin-fixed, paraffin-embedded material. In the present study, NB84 was
      assessed for its usefulness in the differential diagnosis of paediatric small
      cell tumours. It gave reliable staining of 17/19 (90 per cent) neuroblastomas and
      was negative on all other tumours apart from Ewing's sarcomas, of which 9/14 (64
      per cent) showed mainly focal positivity. It is concluded that in association
      with a panel of markers against leucocyte, muscle, epithelial, and neural markers
      NB84 provides considerable assistance in the recognition of neuroblastoma and
      thus is important in enabling the most appropriate therapy to be given.

PMID- 2002425
TI  - Chromosome rearrangement, oncogene activation, and other clonal events in cancer:
      their use in molecular diagnostics.

PMID- 2002426
TI  - In vitro chemotactic response of osteoblast-like osteosarcoma cells to a
      partially purified protein extract of demineralized bone matrix.
AB  - The purpose of this investigation was to evaluate the chemotactic potential of a
      partially purified protein extract from bone matrix when tested against
      osteosarcoma cells with osteoblast characteristics. The chemotactic response of
      ROS 17/2 cells to a lyophilized bovine bone extract purified to "Urist step
      eight" was evaluated in Boyden blind well chambers. A checkerboard design was
      employed to test cell migration against positive, negative, and no concentration
      gradients, thereby controlling the effects of chemokinesis and/or random
      migration on results. The results demonstrate that the partially purified protein
      extract from bovine bone matrix is chemotactic since more cells migrated to
      positive gradients than to negative gradients (P less than .01). The chemotactic
      effect was confirmed by an increase in cell migration toward positive gradients
      of the bone extract compared to cell migration in the presence of no gradient (P
      less than .01). When no gradient was present, the cells exhibited an increased
      response in the presence of equal concentrations of the bone extract (P less than
      .01) indicating a chemokinetic effect. The proteinaceous nature of the
      chemoattractant was confirmed by its susceptibility to trypsin digestion and heat
      exposure.

PMID- 2002427
TI  - The excessive loss of Branemark fixtures in type IV bone: a 5-year analysis.
AB  - The predictability of branemark implants has been well documented. High success
      rates in the maxilla and mandible in fully and partially edentulous patients can
      be expected. A host of factors may be attributed to the etiology of fixture loss.
      However, the quality of bone stands out as the single greatest determinant in
      fixture loss. Types I, II, and III bone offer good strength. Type IV bone has a
      thin cortex and poor medullary strength with low trabecular density. Ninety
      percent of 1,054 implants placed were in Types I, II, and III bone. Only 3% of
      these fixtures were lost; of the 10% of the fixtures placed in Type IV bone, 35%
      failed. Presurgical determination of Type IV bone may be one method to decrease
      implant failure.

PMID- 2002428
TI  - Periodontal healing following guided tissue regeneration with citric acid and
      fibronectin application.
AB  - This study was undertaken to determine the effects of guided tissue regeneration
      (GTR) with and without citric acid conditioning and autologous fibronectin
      application. The study subjects were four female beagle dogs with spontaneous
      periodontitis. The dogs were given thorough root debridement and 4 weeks later,
      mucoperiosteal flaps were raised on both sides of the mandible involving the 2nd,
      3rd, and 4th premolar and 1st molar teeth. After debridement, notches were placed
      on the roots at the level of supporting bone. Citric acid (pH 1) was topically
      applied for 3 minutes on the exposed root surfaces of one side (experimental).
      The roots were irrigated with normal saline solution. Both the root surfaces and
      the inner surface of the flap were then bathed in autologous fibronectin in
      saline. Following this, Gore-Tex periodontal material was adapted to the roots of
      each tooth and sutured. The contralateral side, serving as control, was treated
      by surgery and application of Gore-Tex periodontal material only. All membranes
      were removed 1 month after surgery, and the dogs sacrificed at 3 months. Both
      mesio-distal and bucco-lingual microscopic histological sections were evaluated
      by descriptive histology, and linear measurements and surface area determination
      of the furcal tissues were made. Periodontal healing following the use of GTR
      procedure resulted in an increase in connective tissue and alveolar bone
      regeneration. Adjunctive critic acid plus autologous fibronectin produced
      slightly better results, but these differences were not statistically significant
      for this sample.

PMID- 2002429
TI  - Nifedipine-induced gingival hyperplasia: a clinical and in vitro study.
AB  - Two cases of gingival hyperplasia associated with long-term administration of
      nifedipine, a drug that dilates coronary arteries, are reported. The clinical and
      histopathological features of the gingival hyperplasia induced by nifedipine were
      similar to those induced by phenytoin, an anticonvulsant drug. In the present
      cases, gingival inflammation had developed before drug administration. In one
      case, extensive dental plaque control in addition to surgical removal of the
      overgrown gingival tissues resulted in satisfactory progress without the need to
      discontinue drug administration, suggesting that the preexisting gingival
      inflammation was involved in the development of this periodontal disease. In the
      other case, change from nifedipine to another drug resulted in spontaneous
      recovery, strongly suggesting that the drug had induced the gingival hyperplasia.
      Nifedipine had no direct effects in vitro on proliferation or collagen synthesis
      of gingival fibroblastic cells from one of the patients. Study of these two cases
      suggests that both local inflammatory factors and long-term administration of
      nifedipine were responsible for the gingival hyperplastic changes observed.

PMID- 2002430
TI  - Localization of interleukin-1 beta in human periodontal tissue.
AB  - Interleukin-1 beta (IL-1 beta) is the predominant form of IL-1 produced by
      macrophages. IL-1 beta possesses numerous and diverse biological activities.
      Several of these activities, including fibroblast proliferation, potentiation of
      the immune response, and stimulation of bone resorption may be of relevance to
      the pathogenesis of periodontal disease. This study was designed to examine the
      presence of IL-1 beta in human periodontal tissue. An antiserum directed against
      the N-terminal segment (117-131) of human IL-1 beta was used to detect IL-1 beta
      using immunofluorescent staining techniques. IL-1 beta positive staining cells
      were observed in both normal and diseased tissue and were limited to the lamina
      propria. Brightly staining cells were increased by almost 3-fold in periodontally
      diseased tissue when compared to normal tissue. Low intensity staining cells were
      equally distributed in the normal and diseased specimens. We propose that IL-1
      beta and IL-1 beta produced by cells in periodontal tissues may be related to the
      pathological processes associated with periodontal disease.

PMID- 2002431
TI  - Early healing events at the dentin-connective tissue interface. Light and
      transmission electron microscopy observations.
AB  - The objective of these studies was to follow early healing at the dentin
      connective tissue interface. Small dentin blocks were surgically implanted in
      bone cavities under mucoperiosteal flaps in the edentulous alveolar ridges of
      five beagle dogs at various times. In two separate experiments, wound maturation
      on native dentin surfaces and on citric acid or heparin conditioned dentin
      surfaces was observed. Block specimens including bone, dentin, and surrounding
      soft tissues were obtained at 10 minutes, 1 and 6 hours, and 1, 3, and 7 days
      after flap closure and prepared for light and transmission electron microscopic
      examination of the interface. The very initial attachment to native dentin was
      mediated by a granular precipitate. At 1 and 6 hours, the intercellular matrix
      was more organized with fibrin formation around red blood cell aggregates and at
      the dentin surface. Polymorphonuclear leukocytes were observed throughout the
      interface. Red blood cells were undergoing degradation at day 1 and
      polymorphonuclear cells were prevalent at the dentin surface. The 3-day
      observation interval was characterized by further maturation of the fibrin clot.
      Macrophages were observed near the dentin surface and fibroblasts could be
      identified. The 7-day specimens exhibited areas of cell rich connective tissue
      attachment without inflammatory cells as well as areas showing the fibrin clot in
      various stages of decomposition. These observations suggest that connective
      tissue attachment to dentin surfaces is mediated by adsorption of plasma proteins
      to the surface and subsequent development and maturation of a fibrin clot. The
      sequence of healing events at dentin surfaces conditioned with citric acid or
      heparin was largely similar to healing at native dentin surfaces. However, at day
      1 and later time points, clot adhesion to heparin-conditioned dentin appeared
      compromised, whereas the fibrin clot seemed to adhere to citric acid-conditioned
      dentin at all observation periods. These observations indicate that in the
      absence of mechanical trauma, epithelial proliferation, and infection, wound
      maturation at the dentin-connective tissue interface may not necessarily be
      affected by treatments that either enhance or inhibit clot adhesion to the dentin
      surface.

PMID- 2002432
TI  - Prognosis versus actual outcome: a long-term survey of 100 treated periodontal
      patients under maintenance care.
AB  - One hundred treated periodontal patients under maintenance care were evaluated
      for 5 years, and 39 of these patients were followed for 8 years to determine the
      accuracy of assigned prognoses based on commonly taught clinical criteria. The
      results suggested that this population reflected many of the same characteristics
      seen in well-maintained patients. The ultimate fate of teeth initially labeled as
      hopeless varied substantially, and even though the average prognosis of the teeth
      studied at each interval remained relatively stable over time, individual
      prognosis categories and individual tooth prognoses changed frequently. Possible
      reasons for these shifts are discussed. In conclusion, it was found that
      projections were ineffective in predicting any prognosis other than good, and
      that prognoses tended to be more accurate for single rooted teeth than for multi
      rooted teeth. Further evaluation of the data is needed to determine how each of
      the prognostic indicators relate to the success or failure of our projection.

PMID- 2002433
TI  - Microbiological and immunological aspects of experimental periodontal disease in
      rats: a review article.
AB  - Animal models in which microbiological and immunological aspects of periodontal
      disease can be studied prospectively seem well warranted. The rat bears much
      resemblance to man with respect to periodontal anatomy, development and
      composition of dental plaque, histopathology of periodontal lesions, and basic
      immunobiology. Furthermore, reproducible methods are available for assessment of
      periodontal disease in rats, and detectable periodontal destruction can be
      induced in a few weeks in these animals without traumatizing periodontal tissues
      with ligatures. Experimental periodontitis studies in germ-free rats have
      confirmed the pathogenicity of several suspected periodontal pathogens
      (Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Capnocytophaga
      sputigena, Eikenella corrodens, and Fusobacterium nucleatum). The studies also
      suggest that the number of periodontal pathogens may be higher than generally
      believed, since species like Streptococcus sobrinus and Actinomyces viscosus are
      associated with periodontal bone loss in rats. Studies in rats with congenital or
      induced immune defects indicate that generalized or selective immunosuppression
      at the time of infection with periodontal pathogens may aggravate periodontal
      disease. Studies in immunized rats indicate that periodontal disease can be
      prevented by immunization against periodontal pathogens. However, it is also
      possible by immunization to induce periodontal destruction; i.e., the immune
      system has a destructive potential which should not be overlooked. In the future,
      the rat model may prove valuable for initial screening of antigen preparations
      and immunization regimens in the search for a periodontitis vaccine.

PMID- 2002434
TI  - Microbiological study of HIV-related periodontitis.
AB  - The subgingival microbiota in 14 persons with HIV-periodontitis was examined.
      Subgingival plaque samples were collected with paper points, transported in VMGA
      III, and plated on anaerobic enriched brucella blood agar and various selective
      media. HIV-periodontitis sites revealed Actinobacillus actinomycetemcomitans,
      Wolinella recta, Peptostreptococcus micros, and Bacteroides intermedius, each
      averaging 7% to 16% of the cultivable subgingival flora in positive patients.
      High levels of spirochetes also were detected in diseased sites with phase
      contrast microscopy. Low levels of Candida albicans or enteric Gram-negative rods
      were recovered in the subgingival flora in 7 HIV-periodontitis patients or
      Bacteroides fragilis, Fusobacterium necrophorum, Fusobacterium varium, and
      Eubacterium aerofaciens were recovered in 8 patients. These findings suggest that
      the major components of the subgingival microbial flora in HIV-periodontitis are
      similar to those associated with adult periodontitis in systemically healthy
      persons. However, HIV-periodontitis lesions also may contain organisms which are
      rarely found in common types of periodontitis. The etiological significance of
      specific periodontal organisms in HIV-periodontitis awaits further longitudinal
      study.

PMID- 2002435
TI  - A Rorschach investigation of mothers of behaviorally disturbed infants.
AB  - This investigation focuses on one facet of the interactional family, parent
      child, mother-infant matrix of behaviorally disturbed infants: the personality of
      mother as primary caregiver. Rorschach test behavior of mothers (N = 30) of
      behaviorally disturbed infants were compared with two normative samples. The
      Rorschach test was found to indicate certain atypical psychological patterns
      among these mothers. Differences emerged in intellectual sphere variables: number
      of responses (R), common detail responses (D), rare detail responses (Dd), number
      of accurate form percepts (F+), percentage of form percepts that are accurate
      (F+%), percentage of responses with animal content (A%), and popular percepts
      (P). Other response trends emerged in the affective sphere: percentage of pure
      form responses (F%) and in the interpersonal sphere: whole human content (H) and
      the ratio of the whole human content to human detail content (H:Hd), as well as
      to the test as a whole. Based on these results, hypotheses are generated for
      further investigation, particularly of traits in the areas of cognitive
      processing and the capacity for interpersonal relations.

PMID- 2002436
TI  - Personality assessment of the prelingual, profoundly deaf child or adolescent.
AB  - Personality assessment of children and adolescents experiencing an early,
      profound hearing loss is hampered by the lack of instruments standardized and/or
      developed primarily for use with deaf clients. Further compounding the problem
      are the relatively few psychologists trained in and/or experienced with deaf
      personality assessment. This article reviews the rudimentary requirements for
      personality assessment with the deaf and critiques the available personality
      tests that are either used or useable in assessing the deaf.

PMID- 2002437
TI  - Rorschach assessment of psychological functioning in sexually abused girls.
AB  - We measured psychological functioning in a group of 79 Black females between the
      ages of 5 and 16 and a comparison group of nonabused girls using the Rorschach.
      In addition to Exner's (1985) Comprehensive System, the Elizur (1949) Rorschach
      Content Test Scale (RCT), the Mutuality of Autonomy Scale (MOA; Urist, 1977;
      Urist & Shill, 1982), and the Barrier and Penetration Scales (Fisher & Cleveland,
      1968) were used. Sexually abused girls were found to show more disturbed
      thinking, to experience a higher level of stress relative to their adaptive
      abilities, to describe human relationships more negatively, and to show more
      preoccupation with sexuality than the comparison group. The distress experienced
      by the victimized children was more related to internal mediating variables then
      to abuse characteristics. Sexually abused girls who are cognitively and
      emotionally active also experienced high levels of distress compared to abused
      girls who are psychologically constricted.

PMID- 2002438
TI  - SCL-90-R symptom patterns for adolescent psychiatric inpatients.
AB  - We collected Symptom Check List-90-Revised (SCL-90-R) symptom pattern and
      severity data from a sample of 486 adolescent psychiatric inpatients. Preliminary
      comparison of these data with previously published data for adolescent
      nonpatients suggested no meaningful differences in overall symptom severity,
      although the data suggested higher Positive Symptom Distress Index (PSDI) scores
      for inpatients, less severe somatization and psychoticism symptoms for inpatient
      males compared to nonpatient males, and more severe depressive symptoms for
      inpatient females compared to nonpatient females. Future studies should be
      directed toward further analyses of such data and the development of
      representative and generalizable adolescent inpatient norms for the SCL-90-R.

PMID- 2002439
TI  - Three methods of developing MMPI taxonomies of sexual offenders.
AB  - In a sample of 261 state hospital sexual offenders, Minnesota Multiphasic
      Personality Inventory (MMPI) profiles did not differ for offenders with adult
      victims versus offenders with child victims when offender age was controlled.
      MMPI 2-point analyses for the whole sample revealed five common codes that were
      independent of victim maturity. The sample was randomly divided in half and
      subjected to a cluster-analytic procedure which revealed two MMPI clusters. The
      first cluster was unelevated, with Scale 4 as its high point. The second cluster
      had multiple elevations, with Scales 8, 4, 2, and 7 as the highest scales. These
      clusters were replicated in a cluster analysis of the second half of the sample.
      However, when the sample was recombined, the two clusters were not externally
      validated basis on demographic and criminological variables. The results suggest
      that common psychological variables among sexual offenders may have more
      discriminative value than victim maturity in developing sexual offender
      taxonomies.

PMID- 2002440
TI  - MMPI correlates of Exner's Egocentricity Index in an adolescent psychiatric
      population.
AB  - This research examined the relationship between Exner's Egocentricity Index (EI)
      and Minnesota Multiphasic Personality Inventory (MMPI) Scales 2, 4, and 9 in an
      adolescent psychiatric population. Subjects with a low EI had significantly
      higher MMPI Depression (D) scale elevations compared to those with a high EI.
      Furthermore, of the adolescents who had Scale 2 scores in the clinical range, 68%
      also had an EI in the bottom half of the distribution. There was no relationship
      between the EI and MMPI scales 4 and 9. These findings are discussed in light of
      the generally poor correlations between MMPI and Rorschach variables.

PMID- 2002441
TI  - Lymphangioma of the tongue and the team approach.
AB  - Case report of a 9-year-old female with a 7cm (length) x 4cm (width) x 1cm
      (thick) lymphangioma of the tongue. The tumor caused speech distortion, crowding
      of the anterior maxillary and mandibular teeth, and a prognathic mandible. The
      patient was evaluated by the members of the Cleft Lip and Palate Team at St.
      Christopher's Hospital and underwent a complete resection of the tumor and is
      continuing follow-up care. This case exemplifies the value in a team approach to
      a variety of intraoral problems.

PMID- 2002442
TI  - Reactions of the oral mucosa related to silver amalgam: a review.
AB  - Lesions of the oral mucosa caused by amalgam restorations are rare. They may be
      due to Type IV contact hypersensitivity or toxic reactions to products generated
      by the restorations. Hypersensitivity reactions to amalgam seem to be related to
      mercury in almost all cases. The basis for requiring allergologic examination of
      patients suspected of contact hypersensitivity to amalgam is the presence of
      whitish or reddish, sometimes ulcerative oral mucosal lesions with a clear
      anatomic relation to amalgam fillings. The clinical features of lesions due to
      toxic reactions from amalgam restorations do not differ from those of lesions due
      to contact hypersensitivity, and the diagnosis is obtained by exclusion based on
      a negative patch test. Amalgam accidentally implanted in the oral mucosa results
      in amalgam tattoos which are flat lesions of bluish, blackish or slate grey
      color. Implanted amalgam does not produce an acute tissue response and need not
      be removed except for diagnostic reasons.

PMID- 2002443
TI  - Systemic fluconazole therapy and in vitro adhesion of Candida albicans to human
      buccal epithelial cells.
AB  - The adhesion of Candida albicans to buccal epithelial cells (BEC) from four
      healthy dentate men was studied in vitro 1 wk before, during and after a course
      of systemic fluconazole (50 mg once daily for 1 wk). After 1 wk of fluconazole
      intake candidal adhesion to BEC was significantly reduced and this reduction
      persisted for a week following completion of therapy. Fluconazole, therefore, in
      addition to being an effective antifungal agent may also have a sustained action
      on reducing adherence of candidal species to the oral mucosa.

PMID- 2002444
TI  - Oral melanin pigmentation in 467 Thai and Malaysian people with special emphasis
      on smoker's melanosis.
AB  - At the faculties of dentistry in Chiang Mai, Thailand (CM), and Kuala Lumpur,
      Malaysia (KL), 234 and 233 consecutive out-patients were interviewed concerning
      tobacco and chewing habits and examined for the presence of oral melanin
      pigmentation. Tobacco was regularly used by 32% and 28% of the studied
      populations in CM and KL. Cigarette smoking was the predominant habit, but the
      chewing of betel and tea leaves (miang) and the smoking of banana leaf cigars
      (khi yo) was also registered. The genetically acquired pigmentation dominated.
      Although nearly all non-tobacco users in the Malay and Indian populations had
      oral melanin pigmentation, it was found that tobacco smokers had significantly
      more oral surfaces pigmented than non-tobacco users. Among Thais, the percentage
      of pigmented individuals was significantly higher among tobacco smokers. It was
      concluded that tobacco smoking stimulates oral melanocytes to a higher melanin
      production also in dark-skinned ethnic groups.

PMID- 2002445
TI  - Synthesis of 2-exo- and 2-endo-mecamylamine analogues. Structure-activity
      relationships for nicotinic antagonism in the central nervous system.
AB  - Nine analogues of mecamylamine (2) which differ in the number and substitution
      pattern of methyl groups, were prepared. In four of these analogues the amine
      functionality is in an endo orientation. Enantiomers of 2-endo- and 2-exo-N
      methylfenchylamine (25 and 26, respectively) were also prepared. The
      hydrochloride salts of these compounds were tested for nicotinic antagonism
      relative to mecamylamine in vivo and none was found to be as potent as
      mecamylamine, although a broad range of activity was observed. In general, methyl
      substituents at the C1, C2, and C7 positions of the mecamylamine structure do not
      appear to be significant for antagonistic activity. Methyl substituents at C3,
      however, appear to be very important for activity. Three sets of enantiomers of N
      methylfenchylamine analogues, 28-30, possessing structural features of
      mecamylamine and nicotine were also prepared. These compounds were inactive as
      antagonists. Only a small degree of stereoselectivity was elicited in this
      series, less than that seen with enantiomers of nicotine. Antagonists with the
      exo N-methylamine functionality are slightly more active than the endo isomers.
      The extent to which structural modification might change lipophilicities was
      estimated through calculated partition coefficients; such changes alone appeared
      insufficient to explain differences in activities of the analogues. Lastly, a
      tolerance for a tertiary (dimethyl) amine functionality was demonstrated in
      addition to the lack of tolerance for bulkier substituents at C3 or on the
      nitrogen.

PMID- 2002446
TI  - A potential radioiodinated ligand for androgen receptor: 7 alpha-methyl-17 alpha
      (2'-(E)-iodovinyl)-19-nortestosterone.
AB  - The presence of androgen receptor (AR) in prostate cancer has been linked to the
      androgen-dependent nature of the tumor and has also been shown to have prognostic
      significance; it also appears to be a positive prognostic indicator in breast
      cancer. However, due to the relatively low AR concentrations in most tumors and
      the inherently low specific activity of tritium, the assay of AR based on
      available 3H-ligands is not sensitive enough to measure accurately the amount of
      receptor in small specimens. A 125I-ligand like those available for the estrogen
      and progesterone receptors would be helpful, but development of such a ligand for
      AR has not been very successful. Although several androgen analogues containing
      iodine, bromine, or selenium have been synthesized specifically as potential
      probes for AR, none have shown any significant affinity or specificity for the
      receptor. We therefore undertook the synthesis of new potential AR ligands which
      could be radioiodinated, and determined their affinities for AR (from rat uterus
      and MCF-7 human breast cancer cells) by using a competition assay. We have
      examined both 5 alpha-dihydrotestosterone (5 alpha-DHT) and 19-nortestosterone
      analogues and have identified two such compounds which showed high AR affinity:
      (17 alpha,20E)-17 beta-hydroxy-21-iodo-5 alpha-pregn-20-en-3-one (17 alpha-[E)
      iodovinyl)-5 alpha-DHT, 9) and 17 beta-hydroxy-7 alpha-methyl-(17 alpha,20E)-21
      iodo-19-norpregna-4,20-dien-3- one (7 alpha-methyl-17 alpha-[E)-iodovinyl)-19
      nortestosterone, 11). In fact, the affinity of the latter for human AR was found
      to be superior to that of 5 alpha-DHT itself. These iodovinyl analogues could be
      easily prepared in the radioiodinated form, and should prove to be extremely
      useful in assaying low levels of AR in small specimens.

PMID- 2002447
TI  - Water-soluble cholesteryl-containing phosphorothioate monogalactosides:
      synthesis, properties, and use in lowering blood cholesterol by directing plasma
      lipoproteins to the liver.
AB  - The synthesis of several monogalactoside-terminated phosphorothiolated
      cholesteryl derivatives is described. Monogalactosyl derivatives are coupled by
      phosphorothiolation to cholesterol by using ethylene glycol units as hydrophilic
      spacer moieties. The resulting compounds are easily soluble in water. Upon
      addition of such solutions to human serum (to 2 mM final concentration) the
      compounds are readily incorporated into lipoproteins. Isolated low-density
      lipoprotein (LDL) and high-density lipoprotein (HDL), preloaded with the
      compounds, are rapidly cleared from the circulation by the liver. The hepatic
      association is blocked by N-acetylgalactosamine, which indicates that galactose
      specific recognition sites are responsible for the increased liver uptake. The
      plasma clearance and hepatic uptake of LDL loaded with the compounds is
      substantially higher (about 2-fold) than clearance and uptake of HDL containing
      the compounds. The selectivity of the effects of monogalactoside-terminated
      phosphorothiolated cholesteryl derivatives on the in vivo behavior of LDL as
      compared to that of HDL indicates that these compounds might be used to lower
      specifically LDL levels in patients with a high LDL-cholesterol level.

PMID- 2002448
TI  - N6-substituted adenosine receptor agonists: potential antihypertensive agents.
AB  - Adenosine is known to exert a wide range of pharmacological effects including
      hypotension. This effect of adenosine suggested that modified analogues of
      adenosine might provide useful antihypertensive agents. Thus, we prepared a
      series of novel N6-benzocycloalkyladenosines and studied their receptor binding
      and antihypertensive activity. The structure-activity relationship study shows
      that the adenosine analogues having the hydrophobic phenyl moiety one carbon away
      from the C6-nitrogen have modest affinity and selectivity for the A1 receptor,
      whereas those with the phenyl moiety two carbons away from the C6-nitrogen have
      excellent affinity and selectivity for the A1 receptor. Many of these analogues
      showed excellent antihypertensive activity with a wide range of effects on heart
      rate. There is no direct correlation between the receptor binding affinities and
      antihypertensive activity; however, it is more closely associated with A1 than A2
      affinity. The bradycardic effect of these agonists seems to be due to the A1
      affinity. From this set, compound 3 was further evaluated in secondary
      antihypertensive screens. It lowered the blood pressure dose dependently with
      effects lasting for over 20 h following administration of a 30 mg/kg dose.
      Compound 3 was also effective in lowering blood pressure in a renal hypertensive
      rat model. Thus, appropriately modified N6-substituted adenosines represent a
      novel class of antihypertensive agents.

PMID- 2002449
TI  - Isomeric monomethyl ether derivatives of (RS)-9,10-dihydroxyaporphine
      ("isoapomorphine") as possible products of metabolism by catechol-O
      methyltransferase.
AB  - The isomeric monomethyl ether derivatives of (RS)-9,10-dihydroxyaporphine
      ("isoapomorphine") were synthesized unequivocally as possible metabolites in
      catechol-O-methyltransferase (COMT) mediated O-methylation reactions. In vitro
      incubation studies revealed that isoapomorphine is not a substrate for the COMT
      using experimental conditions under which apomorphine (10,11-dihydroxyaporphine)
      is converted in high yield into its 10-methyl ether, apocodeine. The in vivo
      dopaminergic inactivity of isoapomorphine (as compared with that of apomorphine)
      seems to be due to factors other than metabolic inactivation by COMT.

PMID- 2002450
TI  - The enantiomeric specificity of the antihypertensive activity of 1-(phenylthio)-2
      aminopropane, a synthetic substrate analogue for dopamine beta-monooxygenase.
AB  - We have found that (R,S)-1-(phenylthio)-aminopropane (4a), a synthetic alternate
      substrate for the terminal enzyme of norepinephrine biosynthesis, dopamine beta
      monooxygenase (DBM), is both an indirect sympathomimetic and a potent
      antihypertensive agent in spontaneously hypertensive rats. We demonstrate herein
      that there is a distinct enantiospecific difference in the activities of (R)-1
      (phenylthio)-2-aminopropane (4b) and (S)-1-(phenylthio)-2-aminopropane (4c). We
      find that 4c, the more potent DBM substrate analogue, exhibits both the indirect
      sympathomimetic activity and the antihypertensive activity previously observed
      for the racemate and inhibits the active transport of catecholamines at the nerve
      terminal. In contrast, 4b, which is less potent as a DBM substrate or as an
      inhibitor of catecholamine uptake, does not exhibit an indirect sympathomimetic
      effect and is not an effective antihypertensive agent. These results suggest that
      the greater selectivity of the S enantiomer for both the catecholamine reuptake
      transporter and the target enzyme DBM accounts for its greater potency as an
      indirect-acting sympathomimetic agent as well as its activity as an
      antihypertensive agent. These results are also consistent with the hypothesized
      mechanism of action of this class of sulfur-containing DBM substrate analogues.

PMID- 2002451
TI  - Tetrahydropyridyloxadiazoles: semirigid muscarinic ligands.
AB  - Recent studies have described novel azabicycle-based muscarinic agonists which
      readily penetrate into the central nervous system and are capable of displaying
      high efficacy at cortical sites. The current paper describes the synthesis and
      biochemical assessment of semirigid muscarinic ligands which were used to map the
      requirements of the cortical muscarinic receptor and to study the degree of
      conformational flexibility required to cause receptor activation. Analogues 6 and
      9 provide high-efficacy muscarinic agonists at cortical sites; however, C
      alkylation on the tetrahydropyridine ring resulted in more rigid analogues and
      showed lower predicted efficacy. Molecular mechanics calculations indicated a
      preference for the E rotameric form. This conformation was also observed in the X
      ray crystal structure of ethenyloxadiazole 12. The new compounds were tested in a
      biochemical assay designed to measure receptor affinity and to predict cortical
      efficacy.

PMID- 2002452
TI  - Synthesis and structure-activity relationship of new cephalosporins with amino
      heterocycles at C-7. Dependence of the antibacterial spectrum and beta-lactamase
      stability on the pKa of the C-7 heterocycle.
AB  - Cephalosporins with new aminobenzimidazole and aminoimidazoline heterocycles at C
      7 have been synthesized starting with versatile C-7 isocyanide dihalide synthons.
      The aminobenzimidazoles have a broad spectrum of antibacterial activity,
      including Gram-positive and Gram-negative organisms, but possess limited beta
      lactamase stability. In contrast, the aminoimidazolines have a narrow spectrum of
      antibacterial activity, limited to Gram-negative strains only, but possess
      outstanding beta-lactamase stability. Structure-activity relationships are
      discussed in terms of their dependence on the pKa of the C-7 amino heterocycle,
      basic C-7 residues giving cephalosporins with exceptional beta-lactamase
      stability.

PMID- 2002453
TI  - A comparative NMR study between the macrolide antibiotic roxithromycin and
      erythromycin A with different biological properties.
AB  - 1H nuclear Overhauser enhancement studies and 1H NMR 3J analysis establish the
      similarity between the major solution-state conformation of roxithromycin (1) and
      the erythromycin (2). A major difference between the structure of antibiotics 1
      and 2 is the replacement of the 9-keto group in 2 by a 9-[O-(2,5
      dioxahexyl)oxime] group. The NOE studies show that this oxime chain is oriented
      above the macrocyclic lactone ring and that the oxygen atoms of this chain are
      engaged in tight hydrogen bonding with a water molecule and with the 6- and 11
      hydroxyl groups of the macrocycle. It results in a globular form of the whole
      roxithromycin molecule. These data explain also a relative hydrophobicity of this
      antibiotic. Erythromycin A (2), which presents a less rigid macrocycle with two
      free hydroxyl groups (6-OH and 11-OH), forms a dimer detected by FAB mass
      spectroscopy. 1H and 13C NMR relaxation measurements (T1) for both antibiotics
      show that interresidue hydrogen bonds in roxithromycin reduce the rotational
      freedom of the macrocyclic lactone ring and consequently the motions of
      desosamine and cladinose sugars. In another way, an ionization of the amino
      function occurs in the various media according to the nature of the antibiotic.
      This would allow the reactivity modification of the desosamine unit. In the
      biological study, the modifications of the 455-nm metabolite-cytochrome P-450
      complex formation are observed.

PMID- 2002454
TI  - Carboxylic acids and tetrazoles as isosteric replacements for sulfate in
      cholecystokinin analogues.
AB  - A series of analogues of the satiety-inducing peptide cholecystokinin (CCK-8) was
      prepared in which the sulfated tyrosine required for activation of peripheral
      receptors was replaced with a carboxy(alkyl)- or tetrazolyl(alkyl)-phenylalanine
      to investigate whether an organic acid could serve the role of the sulfate group
      at the receptor. The necessary intermediates were prepared by previously reported
      procedures or by alkylation of carboxy(alkyl)- or tetrazolyl(alkyl)phenylmethyl
      bromides with a glycine-derived anion followed by protecting-group manipulations,
      and these were incorporated into derivatives of acetyl-CCK-7 using solid-phase
      synthesis. Peptide analogues were evaluated in a CCK-binding assay for affinity
      for either peripheral (CCK-A) receptors using homogenated rat pancreatic
      membranes as the receptor source or for central (CCK-B) receptors using bovine
      striatum as the receptor source. They were further evaluated for effects on food
      intake in rats after intraperitoneal (ip) injection. A number of the compounds
      reported are active in the CCK-A receptor binding assay although less potent than
      acetyl-CCK-7 and decrease food intake with comparable potency to acetyl-CCK-7. In
      a meal feeding model designed to assess appetite suppressant activity, acetyl-CCK
      7 has an ED50 of 7 nmol/kg ip, while the ED50s of Ac-Phe(4-CH2CO2H)-Met-Gly-Trp
      Met-Asp-Phe-NH2 (28) and Ac-Phe[4-(tetrazol-5-yl)]-Met-Gly-Trp-Met-Asp-Phe-NH2
      (34) were 9 and 11 nmol/kg ip, respectively. An analogue of 28 lacking the N
      terminal acetamido group, 3-[4-(carboxymethyl)-phenyl]propanoyl-Met-Gly-Trp-Met
      Asp-Phe-NH2 (50), was also active in the meal feeding assay with an ED50 of 3
      nmol/kg ip. Its anorexic effect was blocked by simultaneous administration of the
      CCK-A receptor antagonist MK 329, indicating that the observed anorexic activity
      is mediated by CCK-A receptors. We conclude from this work that the requirement
      for a negative charge at the CCK-A receptor provided in the natural substrate by
      a sulfate group can be satisfied by organic acids.

PMID- 2002455
TI  - Neoglycoproteins as carriers for antiviral drugs: synthesis and analysis of
      protein-drug conjugates.
AB  - In order to investigate whether neoglycoproteins can potentially act as carriers
      for targeting of antiviral drugs to certain cell types in the body, various
      neoglycoproteins were synthesized using thiophosgene-activated p-aminophenyl
      sugar derivatives. These neoglycoproteins were conjugated with the 5'
      monophosphate form of the antiviral drug AZT. For a proper characterization of
      these preparations, both protein and drug content have to be determined.
      Comparison of the Lowry and the Bio-Rad protein assays revealed that for both the
      neoglycoprotein carriers themselves and the AZTMP conjugates, the Lowry assay
      yielded the most reliable and reproducible results. It was demonstrated that both
      the reagent used for drug conjugation (ECDI) as well as the introduction of
      phenyl-sugar groups in the protein interfered with the analysis of bound
      nucleotide as based on spectral differences between protein and protein-drug
      conjugate. Therefore, we developed a rapid HPLC system for determination of the
      drug-protein coupling ratio through acid hydrolysis of the covalently bound
      nucleotide. With the ECDI-mediated conjugation of 5'-monophosphate drug
      derivatives to neoglycoproteins, products with molar ratios of drug to protein
      ranging from 1.2 to 5.6 were obtained. The drug-neoglycoprotein conjugates
      appeared to be fairly stable during storage, in lyophilized form, at -20 degrees
      C. The anti-HIV-1 activity of the neoglycoprotein-drug conjugates, as determined
      in vitro in MT-4 cells, was shown to be dependent on glycosylation of the albumin
      and also on the kind of sugar present in the neoglycoprotein. The anti-HIV-1
      activity of the AZTMP-mannose-albumin conjugate exceeded that of the parent drug
      by more than 4 times.

PMID- 2002456
TI  - Synthesis and biological activity of 5-alkyl-1,7,8-trisubstituted-6
      fluoroquinoline-3-carboxylic acids.
AB  - A series of 5-alkyl-1,7,8-trisubstituted-6-fluoro-1,4-dihydro-4-oxo-3-
      quinolinecarboxylic acids was prepared and evaluated for in vitro and in vivo
      antibacterial activity. When compared to the 5-hydrogen analogues, the presence
      of the 5-methyl group enhanced in vitro potency for those compounds containing a
      cyclopropyl moiety at N1 but decreased potency for those containing an ethyl
      group at N1. Replacing the 5-methyl with a 5-ethyl significantly reduced the
      efficacy. In general, the 5-methyl and 5-hydrogen analogues were equipotent in
      vivo. Several of the 5-methyl-1-cyclopropylquinolones displayed excellent in
      vitro and in vivo activity, warranting further development.

PMID- 2002457
TI  - Beta-substituted beta-phenylpropionyl chymotrypsins. Structural and
      stereochemical features in stable acyl enzymes.
AB  - In order to develop effective alternate substrate inhibitors for the serine
      protease, we have prepared a series of beta-substituted beta-phenylpropionic acid
      esters related to some systems known to form stable acyl enzymes with alpha
      chymotrypsin. Some of these compounds were prepared in enantiomerically pure form
      by asymmetric synthesis. Acyl enzyme species were generated from chymotrypsin by
      reaction with the active esters, and the progress of deacylation was monitored by
      the proflavin displacement assay. In some cases, it was possible to distinguish
      two different deacylation rates that correspond to the two enantiomers. beta
      Phenylpropionic acyl enzymes with beta-substituents that are nonpolar were not
      especially stable, but a number of the polar derivatives and particularly the
      acylamino derivatives showed slow rates of deacylation (kd less than 0.005 min
      1), with three systems showing deacylation enantioselectivities in the range of
      500-1500. These results are consistent with a model in which additional
      stabilization of the acyl enzyme and enantioselectivity in the deacylation
      process derives from an additional hydrogen bond between the acyl enzyme species
      (as an acceptor) and the enzyme (as a donor). A number of active site residues
      that might be involved in this hydrogen bond are discussed.

PMID- 2002458
TI  - Positional effects of sulfation in hirudin and hirudin PA related anticoagulant
      peptides.
AB  - C-Terminal fragment analogues of the leech protein hirudin or the related protein
      hirudin PA block thrombin's cleavage of fibrinogen. Three series of synthetic
      peptides were synthesized to study the effects of sulfation in hirudin-derived
      peptides. Potency of hirudin analogues increased with p-(amino)Phe63, p
      (aminosulfonate)Phe63, and p-(sulfate)Tyr63 substitution in place of Tyr63.
      Sulfation of Tyr56, which in hirudin is normally Phe, resulted in a loss of 1
      order of magnitude in potency. The sulfation of Tyr64 of the hirudin PA related
      analogue resulted in increased potency as for the hirudin analogue. However, in
      this series the p-(amino)Phe64 and p-(amino-sulfonate)Phe64 did not have
      increased potency. In addition to these positional effects, replacing all the Glu
      residues with (O-sulfato)Ser yielded an analogue with full antithrombin potency.

PMID- 2002459
TI  - Adenosine deaminase inhibitors: synthesis and structure-activity relationships of
      imidazole analogues of erythro-9-(2-hydroxy-3-nonyl)adenine.
AB  - A series of erythro-1-(2-hydroxy-3-nonyl)imidazole derivatives have been
      synthesized and evaluated for adenosine deaminase (ADA) inhibitory activity, in
      order to introduce simplifications in the ADA inhibitors erythro-9-(2-hydroxy-3
      nonyl)adenine (EHNA, 1a) and 3-deaza-EHNA (1c). Opening the pyrimidine or
      pyridine ring of EHNA or 3-deaza-EHNA respectively led to compounds which are
      still ADA inhibitors. The most potent compound was erythro-1-(2-hydroxy-3
      nonyl)imidazole-4-carboxamide (5, Ki = 3.53 x 10(-8) M), which provided potential
      donor and acceptor sites for hydrogen bonding. Lack of one of this sites could
      account for the order of potency of all compounds examined in this series.
      Opening the same ring in adenosine and in 3-deazaadenosine led to fully inactive
      compounds. These results support the hypothesis of the existence, at or near the
      enzyme active site, of a hydrophobic region able to bind the erythro-nonyl
      moiety.

PMID- 2002460
TI  - Synthesis and copper-dependent antimycoplasmal activity of amides and amidines
      derived from 2-amino-1,10-phenanthroline.
AB  - A series of both aliphatic and aromatic amides and aromatic amidines derived from
      2-amino-1,10-phenanthroline (3) according to the Topliss scheme were synthesized
      and subsequently tested for antimycoplasmal potency. Although the compounds
      themselves showed no activity, in the presence of a nontoxic copper concentration
      of 40 microM all compounds appeared to be very active against Mycoplasma
      gallisepticum K154. The most active compounds were found in the amide series and
      show growth inhibition in the nanomolar range. These compounds are 4 times more
      active than tylosin, a macrolide antibiotic, which is used therapeutically in
      veterinary practice. In the presence of copper, amides derived from 3 are more
      active than corresponding amidines. Increased activity following derivatization
      of 3 may be due to the presence of a third coordination site for copper in the
      title compounds. Evaluation of biological data revealed that antimycoplasmal
      activity of amides derived from 3 is dependent on lipophilicity. For these amides
      a good linear correlation was found between antimycoplasmal activity and
      hydrophobic fragmental values for substituents considered. This quantitative
      structure-activity relationship study indicated that antimycoplasmal activity was
      increased upon a decrease of these hydrophobic fragmental values.

PMID- 2002461
TI  - 1H-imidazo[4,5-c]quinolin-4-amines: novel non-xanthine adenosine antagonists.
AB  - On the basis of a model we recently developed for the antagonist binding site of
      the adenosine A1 receptor (J. Med. Chem. 1990, 33, 1708-1713), it was predicted
      that 1H-imidazo[4,5-c]quinolin-4-amines would be antagonists of the A1 receptor.
      Furthermore, it was expected that certain hydrophobic substitutions at the 2- and
      4-positions would enhance affinity. Here, we report on the synthesis and the
      adenosine A1 and A2 receptor affinity of substituted 1H-imidazo[4,5-c]quinolin-4
      amines. Some of these compounds have nanomolar affinity for the A1 receptor. The
      structure-activity relationships (SAR) of these compounds are discussed in
      relation to SAR for other adenosine receptor ligands. The 1H-imidazo[4,5
      c]quinolin-4-amines constitute a novel class of non-xanthine adenosine
      antagonists.

PMID- 2002462
TI  - Dual-function radiosensitizers. Alpha-[[(2-bromoethyl)amino]methyl]-2-nitro-1H
      imidazole-1-ethanol and related compounds: preparation via an aziridine
      equivalent.
AB  - An improved synthesis of the dual-function radiosensitizer alpha-[[(2
      bromoethyl)amino]methyl]-2-nitro-1H-imidazole-1-ethanol (2, RB 6145) has been
      developed. Previously, the synthetic difficulties associated with this compound
      limited its attractiveness as a clinical candidate, although its radiosensitizing
      activity in preclinical models warranted its further development. The synthesis
      described uses a 2-oxazolidinone as an aziridine equivalent and provides 2 in 47%
      yield.

PMID- 2002463
TI  - Triazolobenzo- and triazolothienodiazepines as potent antagonists of platelet
      activating factor.
AB  - A series of [1,2,4]triazolo[4,3-alpha][1,4]benzodiazepines bearing an ethynyl
      functionality at the 8-position and the isosteric thieno[3,2
      f][1,2,4]triazolo[4,3-alpha][1,4]diazepines were prepared and evaluated as
      antagonists of platelet activating factor. The effects of substitution were
      explored in in vitro and in vivo test systems designed to measured PAF
      antagonistic activity. Results are discussed and compared with previously
      published data. Many of the compounds had activity superior to WEB 2086, compound
      1. In general, the thieno analogues exhibited better oral activity than the
      corresponding benzodiazepines. The duration of activity upon oral administration
      was modulated by the substitution on the acetylenic side chain. Compounds 71 and
      81 were selected for further pharmacological evaluation as a result of their good
      oral potency and exceptionally long duration of action.

PMID- 2002464
TI  - Effect of hydroxyl group configuration in hydroxyethylamine dipeptide isosteres
      on HIV protease inhibition. Evidence for multiple binding modes.

PMID- 2002465
TI  - L-687,908, a potent hydroxyethylene-containing HIV protease inhibitor.

PMID- 2002466
TI  - Benzocycloalkyl amines as novel C-termini for HIV protease inhibitors.

PMID- 2002467
TI  - Reevaluating equilibrium and kinetic binding parameters for lipophilic drugs
      based on a structural model for drug interaction with biological membranes.

PMID- 2002468
TI  - Synthesis and ligand binding of cocaine isomers at the cocaine receptor.
AB  - The cocaine binding site at the dopamine transporter has been found to be
      stereoselective. Thus, the seven possible stereoisomers of (-)-cocaine have been
      synthesized and found to inhibit [3H]-2 beta-carbomethoxy-3 beta-(4-fluoro
      phenyl)tropane [( 3H]WIN 35,428) with potencies ranging from 1/60 to 1/600 of
      that of (-)-cocaine. The synthesis and characterization of all new compounds is
      presented.

PMID- 2002469
TI  - Renin inhibitors containing conformationally restricted P1-P1' dipeptide
      mimetics.
AB  - A series of renin inhibitors containing lactam-bridged P1-P1' dipeptide mimetics
      based on the ACHPA (4(S)-amino-5-cyclohexyl-3(S)-hydroxypentanoic acid) design
      was studied. The inhibitors were obtained by aldol addition of various lactams
      with N alpha-Boc-L-cyclohexylalaninal, followed by Boc group removal and
      acylation with Boc-Phe-His. The aldol diastereomer having the S configuration at
      the two newly generated stereogenic centers gave optimal enzyme inhibition.
      Potency was further enhanced in the gamma-lactam ring series by substitution with
      small hydrophobic groups to mimic the P1' side chain of the renin substrate.
      Thus, 2(S)-[(Boc-L-phenylalanyl-L-histidyl)amino]-3-cyclohexyl-1(S)-hydroxyl-1 -
      (1,5,5-trimethyl-2-oxopyrrolidin-3(S)-yl)propane (34) has an IC50 of 1.3 nM in
      the human plasma renin assay. A variety of substituents on the lactam nitrogen
      are tolerated and can be used to vary the physical properties of the inhibitor.
      By using a model of the human renin active site, the conformation of 34 in the
      enzyme-inhibitor complex is proposed. This modeled conformation is very similar
      to the solid-state conformation of 2(S)-[(Boc-L-phenylalanyl-L-histidyl)amino]-3
      cyclohexyl-1(S)-hydroxyl- 1-(1-methyl-2-oxopyrrolidin-3(S)-yl)propane (36), the
      structure of which was determined by single-crystal X-ray diffraction analysis.
      The most potent ACH-PA-lactam renin inhibitors show good selectivity when assayed
      against other types of aspartic proteinases. By varying the lactam ring
      substituents, potent and selective inhibitors of cathepsin D and cathepsin E can
      be obtained.

PMID- 2002470
TI  - Syntheses and in vitro evaluation of water-soluble "cationic metalloporphyrin
      ellipticine" molecules having a high affinity for DNA.
AB  - The synthesis of hybrid "cationic metalloporphyrin-intercalator" molecules is
      reported. These molecules are based on 9-methoxyellipticine as intercalator and
      tris-(4-N-methylpyridiniumyl)metalloporphyrins having a 4-aminophenyl or a 4
      hydroxyphenyl group for the attachment of the linker. The effect of the length of
      linker (7-13 bonds), the chemical nature of the linking group (with a carboxamido
      or an ether function), the position of amino group between the two parts of
      hybrid molecules, the number of intercalator moieties (ellipticinium) covalently
      attached to the metalloporphyrin, and the nature of the central metal atom (Mn,
      Fe, Zn) on the biological activity of these hybrid molecules were studied. In
      addition, these molecules have a high affinity for double-stranded DNA (affinity
      constant of hybrid molecule 9Mn,Me = 2.3 x 10(9) M-1 for poly[d(A-T)] and 2.8 x
      10(8) M-1 for poly[d(G-C)] and are cytotoxic against murine leukemia cells L1210
      in vitro (IC50 of 9Mn,Me = 0.8 microM). Their cytotoxicities are dependent on the
      nature of central atom. Iron derivatives are less active than manganese analogues
      and the corresponding zinc derivatives are nearly inactive despite their same
      affinity for nucleic acids. These highly water-soluble hybrid molecules could be
      considered as efficient bleomycin models based on a cationic metalloporphyrin.

PMID- 2002471
TI  - N-(5-fluorobenzothiazol-2-yl)-2-guanidinothiazole-4-carboxamide. A novel,
      systemically active antitumor agent effective against 3LL Lewis lung carcinoma.
AB  - N-(5-Fluorobenzothiazol-2-yl)-2-guanidinothiazole-4-carboxam ide (1) is a member
      of a series of amides found to substantially increase lifespan in mice bearing
      established micrometastatic 3LL Lewis lung carcinoma. Amide 1 is effective after
      either oral or intraperitoneal dosing in acute, subacute, or chronic regimens. 1
      is well tolerated in this model with an excellent therapeutic index relative to
      the cytotoxic anticancer drug adriamycin.

PMID- 2002473
TI  - A new class of calcium antagonists. 2. Synthesis and biological activity of 11
      [[4-[4-(4-fluorophenyl)-1-piperazinyl]butyryl]amino]-6,11- dihydrodibenzo[b,e]
      thiepin maleate and related compounds.
AB  - A series of [(epsilon-aminoalkanoyl)amino]-6,11- dihydrodibenzo[b,e]thiepins and 
      5H-dibenzo[a,d]cycloheptenes and related compounds were synthesized and evaluated
      for calcium antagonistic activity by calcium-induced constriction of potassium
      depolarized rat aorta. Semiempirical molecular orbital calculations of the
      dibenzotricyclic systems indicated that calcium antagonistic activity increased
      with a decrease of the angle between the planes of the two phenyl rings. AM1 net
      charge calculations showed that a neutral or positive charge distribution in the
      bridge portion was necessary for activity. 11-[[4-[4-(4-Fluorophenyl)-1-
      piperazinyl]butyryl]amino]-6,11-dihydrodibenzo[b,e]thiepin maleate (16, AJ-2615)
      showed a more gradual and longer lasting antihypertensive effect than diltiazem
      and nifedipine in spontaneously hypertensive rats (SHR) administered orally.
      Compound 16 also possessed antianginal effects in methacholine-induced ST
      elevation and vasopressin-induced ST depression tests in rats. The alteration of
      the dibenzotricyclic system of 16 to 5H-dibenzo[a,d]cycloheptene (19, 5-[[4-[4-(4
      fluorophenyl)-1-piperazinyl]-butyryl]amino]-5H- dibenzo[a,d]cycloheptene)
      resulted in selectivity for cardiac tissue over vascular tissue, thereby
      conferring antianginal activity without an effect on blood pressure. Antianginal
      potencies of 16 and 19 were equal to or somewhat more potent than those of
      diltiazem.

PMID- 2002472
TI  - Synthesis and smooth muscle relaxant activity of a new series of potassium
      channel activators: 3-amido-1,1-dimethylindan-2-ols.
AB  - The synthesis of a novel series of smooth muscle relaxants which have been shown
      to act via the opening or activation of potassium channels is described.
      Compounds have been evaluated for their ability to inhibit spontaneous tone in
      guinea pig isolated trachealis and structure-activity relationships are
      discussed. One compound in particular, 1,1-dimethyl-5-nitro-3-(2-pyridon-1
      yl)indan-2-ol, (16) was identified as a potent relaxant of airways smooth muscle
      in vitro with IC50 = 0.15 microM and was found to significantly inhibit histamine
      induced dyspnoea in conscious guinea pigs when given orally 30-45 min prior to
      challenge.

PMID- 2002474
TI  - Modeling alcohol metabolism with the DARC/CALPHI system.
AB  - We present our general system for QSAR search, CALPHI (Computer-Aided Law by
      Hyperstructure Investigation) set up in the context of the DARC structural
      language. We use it to construct global, fragmentary, and topological models of
      the capacity of alcohols to undergo glucuronidation. The DARC/PELCO model, more
      precisely and more significantly, explains 98% of the total variance with only
      three parameters, while treating the whole set of primary, secondary, and
      tertiary alcohols, whereas the best previously reported treatment restricted to
      primary alcohols, explains only 90% of the variance with two parameters. It
      provides an explicit and more precise interpretation of alcohol metabolism. The
      PELCO methodology is extended to evaluate the prediction reliability of both
      global and fragmentary models. PELCO leads to more predictions when comparison is
      made at the same level of reliability.

PMID- 2002475
TI  - Specific bradycardic agents. 2. Heteroaromatic modifications in the side chain of
      specific bradycardic benzazepinones: chemistry, pharmacology, and structure
      activity relationships.
AB  - Compound 1 (UL-FS 49) has recently been described as the representative of a
      novel class of antiischemic compounds termed "specific bradycardic agents". In
      search of specific bradycardic agents with different pharmacokinetic profiles,
      heteroaromatic analogues of 1 have been synthesized and evaluated for their
      bradycardic activity, selectivity, and duration of action. The chain length n and
      the nature of the heteroaromatic system of compounds 2 strongly determine the
      biological activities. Unsubstituted benzothiophenes and benzofurans in
      combination with a chain length of n = 2 give the most active bradycardic
      compounds. Some of the new compounds combine high bradycardic potency and
      selectivity with a short duration of action and may thus be useful for the
      development of short-acting specific bradycardic drugs.

PMID- 2002476
TI  - Quinazoline antifolates inhibiting thymidylate synthase: 4-thio-substituted
      analogues.
AB  - We report the synthesis of four new 4-thio-5,8-dideazafolic acid analogues and a
      4-(methylthio) analogue structurally related to the thymidylate synthase (TS)
      inhibitor N10-propargyl-5,8-dideazafolic acid. Three N10-propargyl-4-thio-5,8
      dideazafolic acid analogues had C2 amino, hydrogen, and methyl substituents. A 4
      thio and a 4-(methylthio) compound each with hydrogen at C2 and ethyl at N10 were
      also synthesized. In general, the synthetic route involved thionation of the
      appropriate 4-oxoquinazoline; the sulfur thus introduced was then protected by
      methylation. Further protection with a pivaloyl group was required for the
      quinazoline bearing a 2-amino substituent. The protected quinazolines were
      treated with N-bromosuccinimide and the resulting 6-(bromomethyl) compounds were
      then coupled to the appropriate N-monoalkylated diethyl N-(4-aminobenzoyl)-L
      glutamate in N,N-dimethylacetamide with calcium carbonate as base. The 4-thio-5,8
      dideazafolic acids were obtained by removal of the methylthio group with sodium
      hydrosulfide, followed by deprotection of the carboxyl groups with cold dilute
      alkali. For the compound containing a pivaloyl protecting group, hot dilute
      alkali was used. To obtain the 5,8-dideazafolic acid containing a 4-(methylthio)
      substituent, the corresponding diester was treated with lithium hydroxide which
      selectively deprotected the carboxyl groups. The five compounds were tested as
      inhibitors of L1210 TS. It was found that replacement of the 4-oxygen of the
      quinazoline moiety by sulfur did not alter the TS inhibition. However, the
      introduction of a methylthio substituent at position 4 severely impaired TS
      inhibition. All 4-thio compounds were less cytotoxic to L1210 cells in culture
      than their 4-oxo counterparts.

PMID- 2002477
TI  - Synthesis and antitumor activity of structural analogues of the
      epipodophyllotoxins.
AB  - Several ring-contracted analogues of the antitumor agent etoposide have been
      prepared. The synthesis of the simple indanyl system 3 is described along with
      two bicyclic systems of general structure 4 prepared through a stereoselective
      allylation of the keto-ester 6. A cis-fused lactone analogue 5, which is isomeric
      with the etoposide aglycone, has been synthesized via a dialkylation of the
      indene-2-carboxylate anion. Regiochemical and stereochemical results of these
      alkylations are described. The cytotoxicity of these derivatives toward several
      tumor cell lines is described and generally follows the structure-activity
      relationships known for the agent podophyllotoxin (2).

PMID- 2002478
TI  - Nucleosides and nucleotides. 95. Improved synthesis of 1-(2-azido-2-deoxy-beta-D
      arabinofuranosyl)cytosine (cytarazid) and -thymine. Inhibitory spectrum of
      cytarazid on the growth of various human tumor cells in vitro.
AB  - Reaction of N3-benzoyl-1-[3,5-O-(tetraisopropyldisiloxan-1,3-diyl)-beta- D-
      ribofuranosyl]thymine (4a) with diphenyl phosphorazidate, diethyl
      azodicarboxylate, and triphenylphosphine in tetrahydrofuran afforded N3-benzoyl-1
      [2-azido-2-deoxy-3,5-O- (tetraisopropyldisiloxan-1,3-diyl)-beta-D
      arabinofuranosyl]t hymine (5a) in good yield. After the sequence of deblocking of
      5a gave 1-(2-azido-2-deoxy-beta-D-arabinofuranosyl)thymine (7), it was heated in
      N,N-dimethylformamide to produce 6,2'-imino-1-(2-deoxy-beta-D
      arabinofuranosyl)thymine (8). This reaction disclosed the arabino configuration
      for 5a. Similarly the N3-benzoyluracil derivative 4b was transformed to the
      corresponding 2'-"up"-azidouridine derivative 5b, which was further converted to
      1-(2-azido-2-deoxy-1-beta-D-arabinofuranosyl)cytosine (1, cytarazid). The
      antineoplastic activity of 1 was compared with that of ara-C against various
      human cancer cell lines in vitro.

PMID- 2002479
TI  - Clustering of malformations in the families of South American oral cleft
      neonates.
AB  - The relatives of 741 newborn children with non-syndromic cleft lip with or
      without cleft palate (CL +/- P), of 115 with isolated cleft palate (CP), and of
      equal numbers of appropriate controls were screened for the presence of the same
      or different malformations. The main findings were as follows. (1) The frequency
      of familial cases of CL +/- P (17.3%) was much higher than the prevalence of this
      malformation among the relatives of controls (0.5%). (2) The sibs of CL +/- P
      subjects showed a higher prevalence of this condition than their parents (2.9% v
      1.6%). (3) The degree of genetic determination of this condition should be high
      (70 to 74%), and the data in general favour a multifactorial model of
      inheritance, with different thresholds between sexes. However, the action of
      dominant genes cannot be excluded since selection or dominant genes or both could
      be postulated to explain the parent/sib difference. (4) The frequency of other
      malformations was also significantly raised in the families of CL +/- P probands,
      as compared to controls (12.1% v 6.2%). (5) The prevalence of these other
      malformations was higher among sibs (1.6%) than parents (0.7%) of CL +/- P
      babies. (6) A general susceptibility to malformations and different exposure to
      selective agents may explain these latter findings. (7) None of the comparisons
      involving CP children yielded significant results.

PMID- 2002480
TI  - Familial cutaneous photosensitivity and colitis with lethal outcome.
AB  - Three sibs out of four, born to unrelated parents, developed early cutaneous
      photosensitivity and severe colitis. All of them died from untreatable diarrhoea.
      A fourth boy, whose father was different, did not have the same symptoms. The
      origin of this syndrome remains unclear and, in particular, no metabolic defect
      could be detected.

PMID- 2002481
TI  - Pitfalls in counselling: the craniosynostoses.
AB  - We describe three families to highlight the variability of expression and
      penetrance that can occur in the craniosynostoses. In two of the families, gene
      carriers were only identified in retrospect by looking at photographs of other
      family members. In the third family, identical twins were initially thought to be
      discordant for sagittal craniosynostosis until early skull x rays were examined
      and both were found to be affected. The dilemmas faced when counselling these
      families are discussed.

PMID- 2002482
TI  - Tetrasomy 12p (Pallister-Killian syndrome).

PMID- 2002483
TI  - A malformed child with a recombinant chromosome 7, rec(7) dup p, derived from a
      maternal pericentric inversion inv(7)(p15q36).
AB  - We report a child with facial dysmorphic features, hypoplasia of the external
      genitalia, intestinal malrotation, congenital cardiac defect, and minor limb
      anomalies. Chromosome studies showed a recombinant chromosome 7, rec(7) dup p,
      resulting from a maternal pericentric inversion inv(7)(p15 q36). Thus, this child
      had partial trisomy 7p in addition to a small distal monosomy 7. The clinical
      findings are compared with those found in previous reports of trisomy 7p.
      Finally, some general principles for genetic counselling are discussed.

PMID- 2002484
TI  - Two cases of interstitial deletion 1p.
AB  - We report two cases of interstitial deletion of the short arm of chromosome 1.
      The first was a 10 year old boy whose karyotype was 46,XY,del(1) (p22.1p31.2);
      the second was a 6 month old boy with a chromosome complement of 46,XY,del(1)
      (p22.3p31.3). A number of the malformations observed were common to both cases.
      There has been one previously reported case with the same breakpoints as our case
      1 and a phenotype that was strikingly similar.

PMID- 2002485
TI  - The Ohdo blepharophimosis syndrome: a third case.
AB  - A patient with a syndrome consisting of blepharophimosis, simple ears,
      hypoplastic teeth, developmental delay, and hypotonia is described. Previous case
      reports are reviewed and a differential diagnosis is described. Many of the
      features in the subject are similar to those described in two previous reports
      and they constitute a distinct syndrome.

PMID- 2002486
TI  - Cleft lip and palate, sensorineural deafness, and sacral lipoma in two brothers:
      a possible example of the disorganisation mutant.
AB  - We report two brothers of Chinese origin who have an apparently unique syndrome
      of cleft lip/palate, profound sensorineural deafness, and a sacral lipoma.
      Additional findings which were not common to both were aberrant digital
      appendages on the heel and thigh of one boy and an anterior sacral meningocele
      and dislocated hip in the other. Intelligence is normal in both. Both boys suffer
      from functional constipation but biopsy studies showed no evidence of
      Hirschsprung's disease. The parents, who are normal, are not related. Inheritance
      is probably autosomal or X linked recessive. A possible link with the
      disorganisation mouse mutant is discussed.

PMID- 2002487
TI  - Human homologue for the mouse mutant disorganisation: does it exist?
AB  - We describe a newborn Arab male with defects similar to those seen in mice
      heterozygous for the mutant disorganisation (DS) gene. He had complete absence of
      the left lower limb including the left pelvic bone, hamartomas arising from the
      abdominal wall, a small penis, absent left half of the scrotal sac, absent left
      testicle, anterior displacement of the anus, and multiple vertebral defects. The
      similarity between the proband's anomalies and those found in affected
      heterozygotes for DS support the possibility of a human homologue of the DS gene.

PMID- 2002488
TI  - Unknown syndrome: mental retardation with dysmorphic features, early balding,
      patella luxations, acromicria, and hypogonadism.

PMID- 2002489
TI  - Cornelia de Lange syndrome with ring chromosome 3.

PMID- 2002490
TI  - Linear skin defects and congenital microphthalmia: a new syndrome at Xp22.2.

PMID- 2002491
TI  - Genetic aspects of antibiotic induced deafness: mitochondrial inheritance.
AB  - Analysis of 36 pedigrees with a positive family history of aminoglycoside
      antibiotic induced deafness, ascertained in a population of 483,611 in Zhabei
      District in Shanghai, showed that the susceptibility to antibiotic ototoxicity
      was transmitted by females exclusively, indicating mitochondrial inheritance.
      Reanalysis of 18 other published pedigrees confirmed this conclusion.

PMID- 2002492
TI  - Prenatal diagnosis of myotonic dystrophy using closely linked flanking markers.
AB  - We report on two cases of prenatal diagnosis of myotonic dystrophy (DM), using
      flanking markers APOC2 or CKMM on the proximal side and D19S51 on the distal
      side. By double digestion (TaqI and NcoI) of PCR amplified CKMM, the
      informativeness was increased from a PIC value of 0.57 to 0.69. Altogether, with
      a PIC value of 0.64 for APOC2, 0.69 for CKMM, and 0.27 for D19S51 (BglI),
      presymptomatic and prenatal diagnosis can thus be offered to approximately 24% of
      persons with a risk between 0.0004 and 0.0008 using these flanking markers.

PMID- 2002493
TI  - The origin of a morphologically unidentifiable human supernumerary minichromosome
      traced through sorting, molecular cloning, and in situ hybridisation.
AB  - A supernumerary minichromosome has been detected in a severely malformed patient.
      Attempts at identifying the marker by conventional approaches were unsuccessful.
      The physical isolation of the minichromosome by fluorescence activated sorting,
      molecular cloning of its DNA, and in situ hybridisation experiments performed
      with single copy DNA probes allowed us to show that it was derived from a
      rearrangement involving the centromere and the proximal region of the short arm
      of chromosome 9.

PMID- 2002494
TI  - An analysis of amplified insulin gene products in diabetics of Indian origin.
AB  - We have previously described an increased incidence of the class 3 allele of the
      hypervariable region (HVR) 5' to the insulin gene in south Indian non-insulin
      dependent diabetics; this association is absent in Punjabi Sikhs with this
      disorder. Using the polymerase chain reaction we have amplified parts of the
      insulin gene from 130 subjects to look for mutations which may be in linkage
      disequilibrium with the class 3 allele and hence explain its association with non
      insulin dependent diabetes (NIDDM). In 23 south Indian subjects with NIDDM, using
      the restriction enzyme MboII, a B chain mutant (insulin Chicago) was excluded.
      Two patterns (alpha and beta) were found, representing a PstI polymorphism in the
      3' untranslated region of the insulin gene. In subjects homozygous for the class
      1 allele, the allelic frequency for alpha was 0.94 (143/152) and for beta was
      0.06, in heterozygotes (1,3) alpha 0.63 (54/86) and beta 0.37, and in homozygotes
      for the class 3 allele alpha 0.18 (4/22) and beta 0.82 (p less than 0.001), thus
      establishing linkage disequilibrium between these two loci. No differences in
      allelic frequency were found in the south Indians or Punjabi Sikhs between
      controls and the different types of non-insulin requiring diabetes (NIDDM,
      fibrocalculous pancreatic diabetes and maturity onset diabetes of the young) when
      both groups were matched for insulin genotypes. Thus, although this polymorphism
      in the 3' untranslated region of the insulin gene is in linkage disequilibrium
      with the class 3 allele, it does not appear to be any better at predicting
      diabetes than the class 3 allele itself.

PMID- 2002495
TI  - Identification of a subunit assembly domain in the alpha subunit of Escherichia
      coli RNA polymerase.
AB  - The alpha subunit of Escherichia coli DNA-dependent RNA polymerase is encoded by
      the rpoA gene and plays a major role in enzyme assembly. A set of C-terminal
      deletion mutations of the rpoA gene was constructed. The results of mixed
      reconstitution experiments in vitro, using the truncated alpha polypeptides
      encoded by the rpoA deletion mutants, suggest that the amino-terminal two-thirds
      of alpha subunit is sufficient for the formation of pseudo-core complexes
      containing both beta and beta' subunits.

PMID- 2002496
TI  - Tyr60 variants of Flp recombinase generate conformationally altered protein-DNA
      complexes. Differential activity in full-site and half-site recombinations.
AB  - The tyrosine at position 60 of the Flp recombinase of the Saccharomyces
      cerevisiae plasmid, 2 mu circle, is invariant among site-specific recombinases of
      the "yeast plasmid family". Alterations of this residue give rise to Flp variants
      that show no recombination activity when assayed in vivo in Escherichia coli.
      Upon purification, they bind substrate, execute DNA cleavage and catalyze
      recombination. The efficiency of strand cleavage follows the order: Flp(Y60F)
      greater than Flp greater than Flp(Y60S) greater than Flp(Y60D); efficiency of
      recombination between Flp sites on a linear substrate and a circular one follows
      the order: Flp greater than Flp(Y60F) greater than Flp(Y60S) greater than
      Flp(Y60D). Methylation footprints of the DNA-protein complexes formed by two of
      the Flp variants, Flp(Y60S) and Flp(Y60D), do not show hypermethylation of the G
      residues within the substrate core that is characteristic of complexes formed by
      wild-type Flp. The third variant, Flp(Y60F), causes significant distortion
      (although less than wild-type Flp) of the substrate core, as indicated by
      enhanced G-methylation. Binding profiles with circularly permuted substrates
      indicate that Flp(Y60S) and Flp(Y60D), but not Flp(Y60F), are defective in
      bending substrate DNA. In recombination between two Flp half-sites, the variant
      proteins are significantly more active than in normal full-site recombination.

PMID- 2002497
TI  - Regulation of the F plasmid traY promoter in Escherichia coli by host and plasmid
      factors.
AB  - F plasmid DNA transfer (tra) gene expression in Escherichia coli is regulated by
      chromosome- and F-encoded gene products. To study the relationship among these
      regulatory factors, we constructed low-copy plasmids containing a phi(traY'
      'lacZ)hyb gene that couples beta-galactosidase and Lac permease synthesis to the
      F plasmid traY promoter. Wild-type transformants maintained high levels of beta
      galactosidase over a broad range of culture densities. Primer extension analysis
      of tra mRNA from F'lac and phi(traY'-'lacZ)hyb strains indicated very similar,
      though not identical, transcription initiation sites. Moreover, phi(traY'
      'lacZ)hyb gene expression required both TraJ and SfrA, as does tra gene
      expression in F+ strains. beta-Galactosidase activity was reduced approximately
      30-fold in the absence of TraJ, which could be supplied in cis or in trans. In a
      two-plasmid system in which TraJ was supplied in trans by a lac-traJ operon
      fusion, phi(traY'-'lacZ)hyb expression was a linear, saturable function of traJ
      expression. Enzyme activity was reduced approximately tenfold in sfrA mutants.
      That reduction could not be attributed to an effect on the TraJ level. Several
      other cellular or environmental variables had only a modest effect on phi(traY'
      'lacZ)hyb expression. Hyperexpression was observed at high cell density (twofold)
      and in anaerobic cultures (1.2- to 1.5-fold). In contrast, expression was reduced
      twofold in integration host factor mutants.

PMID- 2002498
TI  - A large number of tRNA genes are symmetrically located in fission yeast
      centromeres.
AB  - We report here that the fission yeast centromere regions in the three chromosomes
      contain no less than 36 symmetrically arranged tRNA-coding sequences, and many of
      them are located within the inner inverted regions that are thought to be
      essential for the centromere function. There are 11 different species of tRNA
      coding sequences, and four of them are identical to those previously known in
      this organism. This high-density distribution of tRNA genes in the centromere
      regions is surprising, as the fission yeast centromeres were thought to form
      transcriptionally inactive structures.

PMID- 2002499
TI  - Aggregation and secondary structure of synthetic amyloid beta A4 peptides of
      Alzheimer's disease.
AB  - The deposition of amyloid beta A4 in the brain is a major pathological hallmark
      of Alzheimer's disease. Amyloid beta A4 is a peptide composed of 42 or 43 amino
      acid residues. In brain, it appears in the form of highly insoluble, filamentous
      aggregates. Using synthetic peptides corresponding to the natural beta A4
      sequence as well as analog peptides, we demonstrate requirements for filament
      formation in vitro. We also determine aggregational properties and the secondary
      structure of beta A4. A comparison of amino-terminally truncated beta A4 peptides
      identifies a peptide spanning residues 10 to 43 as a prototype for amyloid beta
      A4. Infrared spectroscopy of beta A4 peptides in the solid state shows that their
      secondary structure consists of a beta-turn flanked by two strands of
      antiparallel beta-pleated sheet. Analog peptides containing a disulfide bridge
      were designed to stabilize different putative beta-turn positions. Limited
      proteolysis of these analogs allowed a localization of the central beta-turn at
      residues 26 to 29 of the entire sequence. Purified beta A4 peptides are soluble
      in water. Size-exclusion chromatography shows that they form dimers that,
      according to circular dichroism spectroscopy, adopt a beta-sheet conformation.
      Upon addition of salts, the bulk fraction of peptides precipitates and adopts a
      beta-sheet structure. Only a small fraction of peptides remains solubilized. They
      are monomeric and adopt a random coil conformation. This suggests that the
      formation of aggregates depends upon a hydrophobic effect that leads to intra-
      and intermolecular interactions between hydrophobic parts of the beta A4
      sequence. This model is sustained by the properties of beta A4 analogs in which
      hydrophobic residues were substituted. These peptides show a markedly increased
      solubility in salt solutions and have lost the ability to form filaments. In
      contrast, the substitution of hydrophilic residues leads only to small deviations
      in the shape of filaments, indicating that hydrophilic residues contribute to the
      specificity of interactions between beta A4 peptides.

PMID- 2002500
TI  - Supramolecular organization of double-stranded DNA molecules in the columnar
      hexagonal liquid crystalline phase. An electron microscopic analysis using freeze
      fracture methods.
AB  - I present an electron microscopical analysis of the columnar hexagonal liquid
      crystalline phase of DNA. Freeze-fracture methods reveal that this phase is a
      lamellar structure, each layer (30 to 40 A thick) composed of DNA molecules
      aligned in parallel. Numerous defects can be seen in the structure, and their
      nature is determined. I show that they are mainly screw dislocations of both
      handedness. By this method it is possible to follow individual double-stranded
      DNA molecules in this highly packed structure. I show, moreover, that there is a
      local twist between DNA molecules along the screw dislocation lines and that this
      twist can be either right-handed or left-handed. The interest of such
      ultrastructural analysis is discussed in relation to the understanding of
      chromatin structure.

PMID- 2002501
TI  - Database algorithm for generating protein backbone and side-chain co-ordinates
      from a C alpha trace application to model building and detection of co-ordinate
      errors.
AB  - The problem of constructing all-atom model co-ordinates of a protein from an
      outline of the polypeptide chain is encountered in protein structure
      determination by crystallography or nuclear magnetic resonance spectroscopy, in
      model building by homology and in protein design. Here, we present an automatic
      procedure for generating full protein co-ordinates (backbone and, optionally,
      side-chains) given the C alpha trace and amino acid sequence. To construct
      backbones, a protein structure database is first scanned for fragments that
      locally fit the chain trace according to distance criteria. A best path algorithm
      then sifts through these segments and selects an optimal path with minimal
      mismatch at fragment joints. In blind tests, using fully known protein
      structures, backbones (C alpha, C, N, O) can be reconstructed with a reliability
      of 0.4 to 0.6 A root-mean-square position deviation and not more than 0 to 5%
      peptide flips. This accuracy is sufficient to identify possible errors in protein
      co-ordinate sets. To construct full co-ordinates, side-chains are added from a
      library of frequently occurring rotamers using a simple and fast Monte Carlo
      procedure with simulated annealing. In tests on X-ray structures determined at
      better than 2.5 A resolution, the positions of side-chain atoms in the protein
      core (less than 20% relative accessibility) have an accuracy of 1.6 A (r.m.s.
      deviation) and 70% of chi 1 angles are within 30 degrees of the X-ray structure.
      The computer program MaxSprout is available on request.

PMID- 2002502
TI  - Preliminary crystallographic study of a pseudoazurin from methylotrophic
      bacterium, Methylobacterium extorquens AM1.
AB  - Single crystals of pseudoazurin, one of the blue copper proteins produced by
      methylotrophic bacterium Methylobacterium extorquens AM1, have been obtained by
      the method of vapor diffusion with ammonium sulfate as a precipitant at pH 8.0.
      Crystals belong to the orthorhombic system, space group P2(1)2(1)2(1), with unit
      cell dimensions of a = 52.619(4) A, b = 63.280(6) A, c = 35.133(4) A. The
      asymmetric unit includes one molecule of pseudoazurin (Vm = 2.18 A3/dalton). The
      crystals are so stable against X-ray irradiation that diffraction intensities of
      the native crystal up to 1.68 A resolution could be collected from only one
      crystal. Among the many heavy-metal reagents examined, uranyl acetate gave an
      effective isomorphous derivative.

PMID- 2002503
TI  - Comparison of the crystal structures of a flavodoxin in its three oxidation
      states at cryogenic temperatures.
AB  - The focus of this study has been to determine the conformation of the holoprotein
      of recombinant flavodoxin from Desulfovibrio vulgaris with the FMN in each of its
      three oxidation states. The structures of the oxidized state of the wild-type
      flavodoxin at 2.0 A from D. vulgaris was used as a starting model for refinement.
      Diffraction experiments were conducted at low temperature (-150 degrees C) in
      order to maintain the oxidation state of interest throughout the intensity data
      collection. yellow bipyramids by the standard hanging-drop method from 3.2 M
      ammonium sulfate in 0.1 M-Tris-HCl buffer at pH 7.0 with protein concentrations
      ranging from 0.7% to 0.9%. The reduced states of the crystals were achieved
      through the addition of sodium dithionite at pH 7.0 for the semiquinone (semi
      reduced) and at pH 9.0 for the hydroquinone (fully reduced). Data sets consisting
      of one at room temperature (oxidized state) and three at low temperature (each
      oxidation state) were collected on a Nicolet P3F/Xentronics area detector X-ray
      diffractometer system. The four structures, hydroquinone at 2.25 A resolution and
      all others at 1.9 A resolution, were refined by the restrained parameter least
      squares program PROLSQ. The final crystallographic R-values converged to 0.21
      (hydroquinone), 0.20 (semiquinone), 0.20 (oxidized, low temperature), and 0.17
      (oxidized, room temperature). The reduced states of flavodoxin show a different
      conformation of the protein polypeptide chain (Asp61-Gly62) in the vicinity of
      NH(5) of the isoalloxazine group relative to the oxidized state. However, there
      are only slight conformational differences between the semiquinone and
      hydroquinone states. In this report, structural comparisons of the three are
      made, with particular emphasis on the features that might be related to the
      difference in temperature of the diffraction data collections and differences in
      the oxidation state of the FMN.

PMID- 2002504
TI  - Analysis of structural design features in collagen.
AB  - The principles governing the molecular design of collagen have been investigated
      using molecular graphics to link the available sequence and X-ray diffraction
      data. The primary structure is classified into three regions of relevance to the
      intermolecular packing. Functionally important variations are revealed in the
      distribution of the amino acid residues. Solvent accessibility studies show that
      the formation of the triple helix is comparable to the stage of secondary
      structure formation in globular proteins. The remaining hydrophobic interaction
      potential serves to determine the three-dimensional packing of the molecules
      within a fibril. A model for the fibril compatible with the X-ray data is
      suggested. Particular attention is directed onto the boundaries of the overlap
      region designated the T zones. Azimuthal orientations of the helical portions at
      these levels appear to be locked by means of a network of aromatic interactions.

PMID- 2002505
TI  - Crystallization and preliminary crystallographic study of cathepsin D inhibitor
      from potatoes.
AB  - Single crystals of the glycosylated inhibitor of cathepsin D and trypsin isolated
      from potato tubers were obtained using the hanging drop vapor diffusion method
      and ammonium nitrate as precipitant. The crystals exhibit strong F222 pseudo
      symmetry but belong to the orthorhombic space group C222 or C222(1), with cell
      parameters a = 73.8 A, b = 119.9 A and c = 133.2 A with two molecules per
      asymmetric unit. The crystals diffract to a resolution of 2.4 A.

PMID- 2002506
TI  - Proton nuclear magnetic resonance study of the B9(Asp) mutant of human insulin.
      Sequential assignment and secondary structure.
AB  - The sequence-specific 1H nuclear magnetic resonance (n.m.r.) assignment of 49 of
      the 51 amino acid residues of human B9(Asp) insulin in water at low pH is
      reported. Spin systems were identified using a series of two-dimensional n.m.r.
      techniques. For the majority of the amino acid residues with unique spin systems,
      particularly Ala, Thr, Val, Leu, Ile and Lys, the complete spin systems were
      identified. Sequence-specific assignments were obtained from sequential nuclear
      Overhauser enhancement (NOE) connectivities. The results indicate that the
      solution structure of the mutant closely resembles the crystal structure of
      native insulin. Thus, the NOE data reveal three helical domains all consistent
      with the secondary structure of the native human 2Zn insulin in the crystal
      phase. Numerous slowly exchanging amide protons support these structural
      elements, and indicate a relatively stable structure of the protein. A
      corresponding resemblance of the tertiary structures in the two phases is also
      suggested by slowly exchanging amide protons, and by the extreme chemical shift
      values observed for the beta-protons of B15(Leu) that agree with a close contact
      between this residue and the aromatic rings of B24(Phe) and B26(Tyr), as found in
      the crystal structure of the 2Zn insulin. Finally, there are clear indications
      that the B9(Asp) insulin mutant exists primarily as a dimer under the given
      conditions.

PMID- 2002507
TI  - Structure of the core promoter of human and mouse ribosomal RNA gene. Asymmetry
      of species-specific transcription.
AB  - In vitro transcription of the ribosomal RNA gene (rDNA) shows a remarkable
      species specificity such that human and mouse rDNA cannot use heterologous
      extracts of each other. The region that is responsible for this specificity has
      been studied using human-mouse chimeric genes and characteristic structures of
      both core promoters are presented. When the mouse sequence is substituted by the
      corresponding human sequence from upstream, the promoter activity in the mouse
      extract begins to decline at nucleotide -32 or -30, decreasing gradually and is
      lost completely at -19. A similar gradual decrease was noted for the 3' side
      substitution, which started at nucleotide -14 and was completed when up to the
      nucleotide -22 mouse position was replaced by the corresponding sequence from
      human. Thus, in the mouse rDNA core promoter, the sequence that is involved in
      species specificity resides only in a stretch encompassing the non-conserved
      region between the distal conserved sequence (DCS) and the proximal conserved
      sequence (PCS), plus two altered nucleotides in the PCS. When human rDNA is
      transcribed with human cell extract, the mouse sequence cannot substitute for the
      human sequence within the region from nucleotide -43 to +17 without affecting
      promoter activity significantly. This asymmetry of species specificity is due to
      the presence of nucleotides -43, +1 and +17, which are sensitive to change in
      only the human core promoter. The difference in the 5' border is ascribed to the
      species specificity of a transcription factor TFID, which recognizes this region.
      But the large difference of the 3' border is apparently due to another factor,
      possibly RNA polymerase I itself, because this region is not recognized by TFID
      in either human or mouse. Mammalian rDNA core promoter appears to consist of a
      tandem mosaic in which three evolutionarily conserved sequences alternate with
      non-conserved sequences having certain functionally important nucleotides. Not
      only non-conserved sequences and non-conserved nucleotides in conserved
      sequences, but also the spacings between the three conserved regions, play a
      crucial role in species specificity.

PMID- 2002508
TI  - Involvement of "hinge" nucleotides of Xenopus laevis 5 S rRNA in the RNA
      structural organization and in the binding of transcription factor TFIIIA.
AB  - Nucleotides in the bifurcation region of the 5 S rRNA, the junction of the three
      helical domains, play a central role in determining the coaxial stacking
      interactions and tertiary structure of the RNA. We have used site-directed
      mutagenesis of Xenopus laevis oocyte 5 S rRNA to make all possible nucleotide
      substitutions at three positions in loop A (10, 11 and 13) and at the G66.U109
      base-pair at the beginning of helix V. Certain double point mutations were
      constructed to ascertain the relationship between loop A nucleotides and the G.U
      base-pair. The importance of the size of the bifurcation region was tested by the
      creation of a single nucleotide deletion mutant and two single nucleotide
      insertion mutants. The effects of these mutations on the structure and function
      of the 5 S rRNA were determined by solution structure probing of approximately
      half of the mutants with chemical reagents, and by measuring the relative binding
      affinity of each mutant for transcription factor TFIIIA. Proposed structural
      rearrangements in the bifurcation region were tested by using a graphic modeling
      method combining stereochemical constraints and chemical reactivity data. From
      this work, several insights were obtained into the general problem of helix
      stacking and RNA folding at complex bifurcation regions. None of the mutations
      caused an alteration of the coaxial stacking of helix V on helix II proposed for
      the wild-type 5 S rRNA. However, the formation of a Watson-Crick pair between
      nucleotide 13 of loop A and nucleotide 66 at the top of helix V does cause a
      destabilization of the proximal part of this helix. Also, nucleotide 109 at the
      top of helix V will preferentially pair with nucleotide 10 of loop A rather than
      nucleotide 66 when both possibilities are provided, without affecting the
      stability of helix V, even though the G.U pair is disrupted. The effects of these
      mutations on TFIIIA binding indicate that the bifurcation region is critical for
      protein recognition. One important feature of the relationship between 5 S rRNA
      structure and TFIIIA recognition resulting from this study was the observation
      that any mutation that constrains the bifurcation loop results in a reduced
      affinity of the RNA for TFIIIA, unless it is compensated for by an increased
      flexibility elsewhere.

PMID- 2002509
TI  - Structures and organization of major plasma protein genes of the silkworm Bombyx
      mori.
AB  - In the silkworm, Bombyx mori, a group of structurally related proteins, termed
      30K proteins, accumulate in the hemolymph of the last instar larvae. We have
      isolated and characterized three genes, each of which encodes a distinct 30K
      protein component. Each 30K protein gene is composed of a short first exon and a
      protein-coding second exon interspersed by a single intron. The transcription
      initiation site of the 30K protein mRNA was identified at the nucleotide level. A
      typical TATA box exists some 30 base-pairs upstream from the transcription
      initiation site. The 5'-flanking region of each gene also contains octamer-like
      sequences. Restriction mapping analyses revealed that the cloned 46 x 10(3) base
      pair region of the chromosomal DNA bears three 30K protein genes. Several copies
      of highly reiterated retrotransposon-like sequences are present around the 30K
      protein genes. S1 nuclease protection analysis provided evidence that the
      biosynthesis of 30K protein is regulated in a stage-specific manner at the
      transcriptional level in the fat body.

PMID- 2002510
TI  - Detection of Escherichia coli ribosome binding at translation initiation sites in
      the absence of tRNA.
AB  - Binary complexes between messenger RNA and E. coli ribosomes were examined. A
      ribosome-mRNA binary complex on T4 gene 32 mRNA withstood inhibition by
      antibodies against ribosomal protein S1. Anti-S1 blocks ternary complex
      formation, as measured by "extension inhibition" or "toeprinting" analysis, only
      when preincubated with ribosomes prior to mRNA addition and not when anti-S1 was
      added after preincubation of ribosomes and mRNA. The ribosome was directly
      localized in a binary complex on two translation initiation sites by toeprinting
      analysis. In the absence of tRNA the ribosome halted cDNA synthesis by reverse
      transcriptase close to the Shine and Dalgarno sequence. Binary complex formation
      was inhibited by an oligodeoxynucleotide competitor of the Shine and Dalgarno
      sequence.

PMID- 2002511
TI  - Development and utilization of physiologically based pharmacokinetic models for
      toxicological applications.
AB  - Recent advances in physiologically based pharmacokinetic (PB-PK) modeling have
      introduced novel approaches for evaluating toxicological problems. Because PB-PK
      models are amenable to extrapolation of tissue dosimetry, they are increasingly
      being applied to chemical risk assessment. This paper reviews the development of
      PB-PK modeling for toxicological applications. It briefly compares and contrasts
      the fundamental differences between conventional compartmental analysis and PB-PK
      modeling. The theory and principles, data requirements and the methodologies to
      obtain them, and the steps to construct PB-PK models are described. A
      comprehensive listing of PB-PK models for environmental chemicals developed to
      date is referenced. Salient applications of PB-PK modeling to toxicological
      problems are illustrated with examples. Finally, the uncertainties and
      limitations in PB-PK modeling are also discussed.

PMID- 2002512
TI  - Modifying effects of anticancer drugs adriamycin, actinomycin D, and cisplatin on
      N-2-fluorenylacetamide-induced hepatocarcinogenesis in male ACI/N rats.
AB  - The effects of some well-known anticancer agents, adriamycin (ADR), actinomycin D
      (ACT), and cisplatin (CIS), on hepatocarcinogenesis induced by N-2
      fluorenylacetamide (FAA) were examined in male ACI/N rats. Animals were divided
      into 15 groups and treated as follows: group 1, 0.02% FAA diet (13 wk); group 2,
      FAA diet and 0.05% phenobarbital (PB) diet (16 wk); group 3, FAA diet and ADR (3
      ip injections of 1.00 mg/kg body weight/wk); group 4, FAA, ADR, and PB; group 5,
      FAA and ACT (3 ip injections of 0.02 mg/kg body weight/wk); group 6, FAA, ACT,
      and PB; group 7, FAA and CIS (3 ip injections of 1.00 mg/kg body weight/wk);
      group 8, FAA, CIS, and PB; group 9, ADR; group 10, ADR and PB; group 11, ACT;
      group 12, ACT and PB; group 13, CIS; group 14, CIS and PB; group 15,
      nontreatment. At the end of the experiment (30 wk), the incidence of
      preneoplastic and neoplastic hepatocellular lesions was evaluated. All three
      tested compounds, especially CIS, inhibited the development of preneoplastic and
      neoplastic liver lesions, indicating CIS could be valuable as a therapeutic agent
      for hepatocellular malignancies.

PMID- 2002513
TI  - Assessment of the hepatotoxicity of acute and short-term exposure to inhaled p
      xylene in F-344 rats.
AB  - Due to the ubiquitous presence of p-xylene in air and the existing uncertainty
      regarding its hepatotoxic potential, we examined the effect of acute and short
      term exposure to inhaled p-xylene on the liver. Male F-344 rats were exposed to 0
      or to 1600 ppm p-xylene, 6 h/d, for 1 or 3 d. Exposure to inhaled p-xylene caused
      no histopathological evidence of hepatic damage and had little or no effect on
      the serum levels of aspartate aminotransferase, alanine aminotransferase, lactate
      dehydrogenase, ornithine carbamyl transferase, alkaline phosphatase, and total
      bilirubin. Exposure to p-xylene for 1 or 3 d resulted in an increase in relative
      liver weight on d 1 post-exposure. The concentration of hepatic cytochrome P-450
      was increased by both p-xylene exposure regimens on d 1 postexposure and had
      returned to control levels by d 3 following the single p-xylene exposure and by d
      2 following the 3-d exposure. These observations provide consistent evidence that
      acute and short-term exposure to 1600 ppm p-xylene by inhalation did not produce
      overt hepatotoxicity but resulted in a significant increase in the concentration
      of hepatic cytochrome P-450, the principal enzyme system involved in the
      metabolic biotransformation of xenobiotics.

PMID- 2002514
TI  - Developmental toxicity of methylamines in mice.
AB  - Monomethylamine (MMA), dimethylamine (DMA), and trimethylamine (TMA) are
      endogenous substances as well as metabolites of methyl isocyanate, the chemical
      involved in the 1984 accident at Bhopal, India. Although methylamines exert
      several toxic effects including inhibition of protein turnover and oocyte RNA
      synthesis, their reproductive toxicity has not been investigated. We therefore
      studied the possible developmental toxicity of these amines using pregnant CD-1
      mice and mouse embryo culture as experimental models. Intraperitoneal injections
      (daily from d 1 to 17 of gestation) of TMA at 2.5 and 5 mmol/kg/d significantly
      (p less than .001) decreased fetal body weight but not the placental weight or
      maternal body weight gain; however, 5 of 11 mice treated with 5 mmol/kg TMA died.
      Similar treatment with DMA and MMA did not exert any obvious maternal or fetal
      effects. All three methylamines, when added to embryos in culture, caused dose
      dependent decreases in size, DNA, RNA, and protein content as well as embryo
      survival; the order of toxicity was TMA greater than DMA greater than MMA. The
      ability of methylamines to adversely affect fetal development suggests that these
      amines, especially trimethylamine, may act as endogenous teratogens under certain
      conditions.

PMID- 2002515
TI  - Dioxin contamination and growth and development in great blue heron embryos.
AB  - A great blue heron colony located near a pulp mill in British Columbia failed to
      fledge young in 1987, with a concurrent sharp increase in polychlorinated dibenzo
      p-dioxin (PCDD) and polychlorinated dibenzofuran (PCDF) levels in their eggs. In
      1988 we tested the hypothesis that the PCDD and PCDF contamination caused
      reproductive failure by increasing mortality of the heron embryos in ovo. Pairs
      of great blue heron eggs were collected from three British Columbia colonies with
      low, intermediate, and high levels of dioxin contamination: Nicomekl, Vancouver,
      and Crofton, respectively. One egg of each pair was incubated under laboratory
      conditions at the University of British Columbia (UBC) while the other egg was
      analyzed for PCDDs and PCDFs. All incubated eggs were fertile. All eggs from the
      Nicomekl colony hatched, while 13 of 14 eggs from Vancouver and 12 of 13 eggs
      from Crofton hatched. Subcutaneous edema was observed in 4 of 12 chicks from
      Crofton and 2 of 13 chicks from Vancouver. No edema was seen in the chicks from
      Nicomekl. There was a small, but significant, negative regression of plasma
      calcium concentration, yolk-free body weight, tibia length, wet, dry, and ash
      weight, beak length, and kidney and stomach weight of the hatched chicks on the
      tetrachlorodibenzo-p-dioxin (TCDD) level of the paired eggs. Fewer down follicles
      were present on the heads of TCDD-contaminated chicks. Hence while dioxins did
      not cause mortality of the heron embryos in ovo, the depression of growth and the
      presence of edema are suggestive that dioxins at the levels found in the
      environment have an adverse effect on the development of great blue heron
      embryos.

PMID- 2002516
TI  - Lack of neuropathological changes in rats after exposure to butyl benzyl
      phthalate.
AB  - Butyl benzyl phthalate (BBP; Santicizer 160 Plasticizer) was fed to 3 groups of
      10 male and 10 female Charles River CD rats for 6 wk at target doses of 500,
      1500, and 3000 mg/kg/d. Control groups of 6 males and 6 females received
      untreated diets for the same period. Body weight gains were decreased at the 1500
      and 3000 mg/kg/d levels. Hindlimb stiffness was noted at the 3000 mg/kg/d level
      and was more prevalent in males. Stiffness was apparently reversed after
      withdrawal from BBP exposure for 2 d. Microscopic examination of central and
      peripheral nervous system tissues did not reveal any compound-related
      pathological changes. Thus, there were no morphological changes in the nervous
      system that could be related to the apparently reversible hindlimb stiffness.

PMID- 2002517
TI  - Harrison Lloyd McLaughlin, M.D., F.A.C.S.: the sixth Alan Deforest Smith memorial
      lecture.

PMID- 2002518
TI  - Treatment of mice with sepsis following irradiation and trauma with antibiotics
      and synthetic trehalose dicorynomycolate (S-TDCM).
AB  - Compromise of antimicrobial defenses by irradiation can result in sepsis and
      death. Additional trauma can further predispose patients to infection and thus
      increase mortality. We recently showed that injection of synthetic trehalose
      dicorynomycolate (S-TDCM) significantly augments resistance to infection and
      increases survival of mice compromised either by whole-body irradiation with
      gamma radiation or equal mixtures of fission neutron and gamma radiation. In this
      study, C3H/HeN mice were given a lethal dose of gamma radiation (8.0 Gy) and an
      open wound (15% total body surface area [TBSA]) 1 hr later while anesthetized.
      Irradiated/wounded mice became more severely leukopenic and thrombocytopenic than
      mice exposed to radiation alone, and died from natural wound infection and sepsis
      within 7 days. S-TDCM given 1 hr postirradiation increased survival of mice
      exposed to radiation alone. However, this treatment did not increase survival of
      the irradiated/wounded mice. Systemic antibiotic therapy with gentamicin or
      ofloxacin for 10 days significantly increased survival time compared with
      untreated irradiated/wounded mice (p less than 0.01). Combination therapy with
      topical gentamicin cream and systemic oxacillin increased survival from 0% to
      100%. Treatment with S-TDCM combined with the suboptimal treatment of topical and
      systemic gentamicin increased survival compared with antibiotic treatment alone.
      These studies demonstrate that post-trauma therapy with S-TDCM and antibiotics
      augments resistance to infection in immunocompromised mice. The data suggest that
      therapies which combine stimulation of nonspecific host defense mechanisms with
      antibiotics may increase survival of irradiated patients inflicted with
      accidental or surgical trauma.

PMID- 2002519
TI  - Subtrochanteric fractures treated with interlocking nailing.
AB  - In a prospective study of 31 subtrochanteric fractures treated with Grosse-Kempf
      interlocking nails with a followup period of at least 1 year, there was a 87.1%
      (27/31) union rate, and a union period of 4.2 +/- 1.8 months. Knee range of
      motion in 28 acute traumatic cases was on average 127.5 +/- 23.0 degrees. The
      significant complications included: nail breakage, 3.2% (1/31); nonunion without
      nail breakage, 9.7% (3/31); neglected femoral fracture with malunion, 3.2%
      (1/31). The interlocking nailing has the advantages of: a) closed method, b)
      weight-sharing principle, c) shortening prevention, d) non-rigid fixation. From
      the theoretical and clinical comparison among the various implants, we conclude
      that closed interlocking nailing is one of the better instruments for
      subtrochanteric fracture treatment, and moreover, the most reasonable of all.
      However, for the higher level subtrochanteric fractures, reconstruction-style
      locking nails should be chosen.

PMID- 2002520
TI  - Degenerative lesions in the articular cartilage after meniscectomy: preliminary
      experimental study in dogs.
AB  - Articular cartilage degeneration was studied in an experimental model including
      68 knees of adult dogs on which five different types of medial meniscectomy had
      been performed with a followup period of 10 to 450 days. The results were
      assessed by macroscopic, radiologic, and histologic methods. The degenerative
      lesions increased proportionally to the amount of meniscal tissue resected and
      the duration of observation. These lesions proved to be more intense at the
      tibial plateau compared to the femoral condyle. For both joint surfaces the
      predominant location was the central zone. Considering the degenerative process
      by the articular cartilage after total meniscectomy, maximum preservation of
      meniscal tissue is recommended.

PMID- 2002521
TI  - Significance of magnetic resonance imaging in acute head injury.
AB  - One hundred seventy-seven patients who had incurred head trauma were studied with
      magnetic resonance imaging (MRI). Patients varied from those with mild injury
      without any focal neurological deficit to those with severe injury with post
      traumatic coma. Altogether, 177 lesions were demonstrated by MRI in 123 of 177
      patients within 3 days of injury using T2-weighted (SE2000/40,2000/111) and T1
      weighted (IR1500/500/40) multislice sequences. In contrast, computerized
      tomography (CT) demonstrated 103 lesions in 90 patients. MRI was superior to CT
      in the diagnosis of nonhemorrhagic contusions demonstrated as a high-intensity
      area on T2-weighted imaging. MRI provided some information to evaluate the
      severity of diffuse axonal injury or to predict delayed traumatic intracerebral
      hematoma (DTICH).

PMID- 2002522
TI  - Alterations of the immune system following splenectomy in childhood.
AB  - After splenectomy due to blunt abdominal trauma, splenectomized children showed a
      restricted pattern of T-cell immunodeficiency compared to age and sex-matched
      normal children. Peripheral blood total (CD3) T-cell counts of 11 splenectomized
      children of 43%, double positive helper (CD4) inducer subpopulation (CD29) cell
      counts of nine splenectomized children of 7%, and phytohemagglutinin (PHA)
      induced T-cell proliferation of 11 splenectomized children of 53,206 c.p.m. were
      significantly (p less than 0.05) lower than values of normal children (61% CD3
      cells, n = 12; 13% CD4CD29 cells, n = 11; 107,832 c.p.m. PHA-induced
      proliferation, n = 12). The deficit of CD4CD29 cell numbers may be due to
      impaired maturation of these particular CD4 lymphocytes and may explain
      diminished PHA-induced proliferation in small children. The significantly higher
      B-lymphocyte counts of splenectomized children (21%, n = 11; 558 cells/mm3, n =
      10) compared with 12 normal children (14%; 329 cells/mm3) may be due to loss of
      the reservoir function of the spleen.

PMID- 2002523
TI  - Clenbuterol decreases catabolism and increases hypermetabolism in burned rats.
AB  - Following a 30% body surface area full-thickness open-flame burn, rats exhibited
      hypermetabolism, body weight loss, and muscle catabolism. Twenty-one days of
      treatment of one group of burned rats with the selective beta 2-adrenergic
      agonist, clenbuterol, increased resting energy expenditure and normalized body
      weight gain, muscle mass, and muscle protein content. Conversely, similar
      treatment of another group of burned rats with the long-acting beta-adrenergic
      antagonist, nadolol, reduced muscle mass, while having no effect on resting
      energy expenditure, body weight gain, or muscle protein content. These results
      demonstrate that hypermetabolism does not invariably result in loss of lean body
      mass and suggest that clenbuterol may be useful in preserving muscle mass and
      protein in catabolic diseases.

PMID- 2002524
TI  - Post-traumatic basal ganglia hemorrhage: analysis of 52 patients with emphasis on
      the final outcome.
AB  - A series of 52 patients suffering post-traumatic basal ganglia hemorrhage (BGH)
      after closed head injury is reviewed. Post-traumatic BGH was associated with
      other intracranial lesions in most cases. The outcome in this series is rather
      good, with 53.8% of patients having a functional survival. Radiologically, the
      post-traumatic intraventricular hemorrhage (IVH) and brainstem hemorrhage usually
      coexisted with a poor outcome. Old age (greater than 60), abnormal pupil
      reaction, impaired oculocephalic response, and abnormal motor response to pain
      stimuli are reliable clinical hallmarks for poor prognosis.

PMID- 2002525
TI  - Achilles tendon repair: a new method of Achilles tendon repair tested on
      cadaverous materials.
AB  - Conventional suture techniques were compared with a new and modified continuous
      six-strand suture technique (CSSS) in laboratory tests on cadaverous Achilles
      tendons. The techniques were compared with regard to gapping resistance and
      rupture point. The CSSS technique had significantly greater tensile strength and
      gapping resistance than the Mason and Bunnell techniques.

PMID- 2002526
TI  - Splenic artery ligation for splenic salvage: clinical experience and immune
      function.
AB  - Documentation of overwhelming post-splenectomy sepsis, characterized by infection
      from encapsulated organisms, has led to development of surgical techniques for
      preservation of the injured spleen to maintain splenic clearance of encapsulated,
      opsonized organisms from the circulation. In this study splenic artery ligation
      (SAL) was performed as an adjunct to successful splenorrhaphy in 20 adults
      suffering blunt splenic injury. There were no deaths and no reoperations. Twenty
      units of blood were transfused in ten patients. Splenic removal of blood-borne
      opsonized particles was measured as the clearance of anti-Rh-antibody-coated 51Cr
      radiolabeled autologous red blood cells from the circulation in five SAL patients
      and nine normal volunteers. The clearance of opsonized red cells 120 minutes
      after injection was not different (40 +/- 7% of injected dose in controls, 40 +/-
      4% in SAL patients). These results demonstrate that SAL can safely be applied as
      an adjunct to splenorrhaphy and that SAL does not diminish splenic clearance of
      opsonized particles from the circulation.

PMID- 2002527
TI  - Class C firework injuries in a pediatric population.
AB  - Class C fireworks are those which can be readily purchased by the public. Between
      July 1971 and August 1988, 23 patients were admitted to our institution with
      firework injuries. Fourteen patients (60.9%) sustained injuries related to Class
      C fireworks. All patients were males with a mean age of 9.0 +/- 3.6 years, with a
      total body surface area (TBSA) burn of 18 +/- 20% with 10 +/- 15% being full
      thickness. Thirteen of the 14 patients required hospitalization. Five patients
      were admitted acutely and eight patients were referred to our institution at
      least 3 days postinjury. All patients required operative intervention in order to
      obtain wound closure. Patients admitted acutely showed a decrease in length of
      hospital stay and patient morbidity when compared to referral patients. Our data
      suggest that class C firework injuries, although small in terms of TBSA burned,
      result in full-thickness wounds that warrant aggressive surgical management.

PMID- 2002528
TI  - Pediatric bicycle trauma.
AB  - Bicycle-related trauma is a serious pediatric problem. Serious injuries and even
      fatalities can occur, and care must be taken to avoid undertreating these
      patients. In an effort to further define the problem, 201 consecutive patients
      admitted for bicycle trauma were reviewed. The patients ranged in age from 3 to
      16 years and 76% (153/201) were male. Head trauma was the most common admission
      diagnosis (99/201; 49%). Fourteen per cent (28/201) were admitted to the
      Intensive Care Unit and 23% (47/201) required an operative procedure. The average
      hospital stay was 3 days; however, patients who were admitted at least 24 hours
      after injury had an average hospital stay of 7 days.

PMID- 2002529
TI  - Repair of the torn descending thoracic aorta using the centrifugal pump with
      partial left heart bypass: technical note.

PMID- 2002530
TI  - Carotid and vertebral artery injury in survivors of atlanto-occipital
      dislocation: case reports and literature review.
AB  - Atlanto-occipital dislocation (AOD) usually results in immediate death from
      transection of the upper cervical spinal cord near the spinomedullary junction.
      However, over the last several decades increasing numbers of AOD survivors have
      been identified. Although many of these patients initially demonstrate profound
      neurologic deficits, a number who survive have regained most or all neurologic
      functions, indicating that they did not suffer mechanical disruption of the
      spinal cord at the time of AOD. In the survivors, a growing body of evidence
      indicates that many of the initial neurologic deficits are related to vascular
      injury to the carotid or vertebral arteries and their branches. We recently
      encountered three AOD survivors with no evidence of mechanical injury to the
      spinal cord in which angiography demonstrated vascular injury to the internal
      carotid artery in the form of vasospasm in one case and to the vertebral arteries
      in the forms of focal stenosis at the site of dural penetration, focal stenosis
      and distal vasospasm, and focal stenosis with distal intimal flap and dissection
      in one case each. Autopsy after one of the three died after cardiac arrest
      demonstrated diffuse infarction of the cerebrum, cerebellum, midbrain, brainstem,
      and upper cervical spinal cord without evidence of mechanical laceration or
      transection of the spinal cord. Recovery of neurologic function in two cases
      following prompt immobilization and angiography suggests that neurologic deficits
      secondary to vascular injury are potentially reversible.

PMID- 2002531
TI  - Warning: fatal reaction to the use of fibrin glue in deep hepatic wounds. Case
      reports.
AB  - Two cases of severe hypotension following the use of fibrin glue for hemostasis
      in hepatic injuries are reported. A systemic reaction to bovine thrombin via
      large venous lacerations is suspected. A preliminary animal study supports this
      hypothesis. Caution is advised in the use of fibrin glue for hemostasis in deep
      hepatic wounds.

PMID- 2002532
TI  - Traumatic popliteal artery pseudoaneurysms: case report and review of the
      literature.
AB  - Traumatic pseudoaneurysms of the popliteal artery are an uncommon late
      complication of arterial injury. Although reviewed extensively in wartime, they
      occur less frequently in civilian trauma and have accordingly been less
      frequently studied. A case report of a traumatic popliteal artery pseudoaneurysm
      and review of the literature are presented.

PMID- 2002533
TI  - Irreducible skin penetration of the ulnar head in Colles fracture--case report.
AB  - Three cases out of four of skin penetration by the ulnar head associated with
      Colles fractures were found to be irreducible. On exploration they had identical
      pathologic anatomy, viz, buttonholing of the ulnar head between the flexor carpi
      ulnaris, flexor digitorum profundus, pronator quadratus, and the flexor
      retinaculum. Incising the flexor retinaculum facilitated reduction.

PMID- 2002534
TI  - Rhabdomyolysis and renal failure following a wolf attack: case report.
AB  - Trauma-induced rhabdomyolysis and myoglobinuric renal failure are well
      recognized. The mechanism of trauma in reported cases has been burns, crush
      injuries, or compression syndromes. We report a case of myoglobinuric renal
      failure in a 5-year-old boy who suffered primarily lacerations and penetrating
      wounds from a wolf attack. We are unaware of any other reports of nonvenomous
      bites or penetrating trauma causing rhabdomyolysis and myoglobinuric renal
      failure. Early suspicion, diagnosis, and treatment of this condition result in an
      excellent prognosis. Pathogenesis, treatment, and a review of the literature are
      presented.

PMID- 2002535
TI  - Splenic laceration secondary to closed chest massage: successful recognition and
      management--case report.
AB  - Closed chest massage can be a lifesaving act. Performed incorrectly or by
      untrained individuals it can lead to life-threatening complications. Successful
      recognition and treatment of a lacerated spleen secondary to cardiopulmonary
      resuscitation is reported. All patients surviving CPR should be screened for
      potential complications.

PMID- 2002536
TI  - An unusual type of perilunate dislocation: case report.

PMID- 2002537
TI  - Splenic conservation in distal pancreatic injury: stay away from the hilum!

PMID- 2002538
TI  - Woodchuck hepatitis virus is a more efficient oncogenic agent than ground
      squirrel hepatitis virus in a common host.
AB  - Chronic infection with hepatitis B viruses (hepadnaviruses) is a major cause of
      hepatocellular carcinoma (HCC), but the incubation time varies from 1 to 2 years
      to several decades in different host species infected with indigenous viruses. To
      discern the influence of viral and host factors on the kinetics of induction of
      HCC, we exploited the recent observation that ground squirrel hepatitis virus
      (GSHV) is infectious in woodchucks (C. Seeger, P. L. Marion, D. Ganem, and H. E.
      Varmus, J. Virol. 61:3241-3247, 1987) to compare the pathogenic potential of GSHV
      and woodchuck hepatitis virus (WHV) in chronically infected woodchucks. Chronic
      GSHV infection in woodchucks produces mild to moderate portal hepatitis, similar
      to that observed in woodchucks chronically infected with WHV. However, HCC
      developed in GSHV carriers about 18 months later than in WHV carriers. Thus,
      although both viruses are oncogenic in woodchucks, GSHV and WHV differ in
      oncogenic determinants that can affect the kinetics of appearance of HCC in
      chronically infected animals.

PMID- 2002539
TI  - Host range mutant of human immunodeficiency virus type 1: modification of cell
      tropism by a single point mutation at the neutralization epitope in the env gene.
AB  - We have isolated a variant of human immunodeficiency virus type 1 (HIV-1) which
      is highly infectious to fibroblastlike cells (BT cells) derived from human brain
      as well as CD4-positive T cells. This variant HIV-1, named HIV[GUN-1V], was
      obtained by infecting BT cells with a prototype HIV-1 isolate, named HIV[GUN
      1WT], which is highly infectious to T cells but barely infectious to BT cells.
      HIV[GUN-1V] infects BT cells productively and this infection appeared to be
      mediated by CD4. To elucidate the viral gene responsible for the host range
      difference between the variant and prototype HIV-1s, we cloned and analyzed the
      provirus genomes of the two viruses. Examination of the infectivities of BT cells
      by various recombinant viruses and analyses of the nucleotide sequences of
      HIV[GUN-1V] and HIV[GUN-1WT] showed that a single nucleotide exchange was
      responsible for their difference in infectivity of BT cells: HIV[GUN-1V] contains
      a thymine residue instead of the cytosine residue in HIV[GUN-1WT] at position 931
      of the env coding sequence. Replacement of cytosine by thymine at this position
      of the env coding sequence of the HIV[GUN-1WT] genome induced the ability to
      infect BT cells. The base exchange at this position was expected to change amino
      acid 311 of the envelope glycoprotein, gp120, from proline to serine, which is
      located in a variable region containing type-specific immunodominant epitopes.
      Thus, HIV[GUN-1V] acquired a wider host range than HIV[GUN-1WT] by a single point
      mutation in the env gene.

PMID- 2002540
TI  - Mapping the anatomy of the immunodominant domain of the human immunodeficiency
      virus gp41 transmembrane protein: peptide conformation analysis using monoclonal
      antibodies and proton nuclear magnetic resonance spectroscopy.
AB  - Thirty-six monoclonal antibodies from mice and three from rats were raised
      against a peptide corresponding to the immunodominant domain of the transmembrane
      gp41 protein of human immunodeficiency virus (HIV) type 1 (LGLWGCSGKLIC; amino
      acid residues 598 to 609). Of these, three monoclonal antibodies from the mice
      and one from a rat also reacted with the corresponding peptide derived from the
      HIV type 2 transmembrane gp41 protein (amino acid residues 593 to 603;
      NSWGCAFRQVC). Immunochemical studies using a variety of synthetic peptides
      indicated that the cross-reactivity was due to antibody binding to CSGKLIC of HIV
      type 1 or CAFRQVC of HIV type 2. Single amino acid substitutions for a cysteine
      at either the amino or the carboxy end of the peptide interrupted antibody
      binding, indicating that the site recognized was the Cys-XXXXX-Cys loop. Similar
      results were obtained when the 11-mer HIV type 2 gp41 peptide (amino acids 593 to
      603) was inoculated into mice to raise monoclonal antibodies. In this instance,
      of 30 monoclonal antibodies developed, 4 reacted with both HIV type 1 and HIV
      type 2 peptides. The conformation of a seven-residue peptide, CSGKLIC,
      corresponding to residues 603 to 609 of the gp41 immunodominant epitope of HIV-1
      was investigated by proton nuclear magnetic resonance spectroscopy. The
      immunologically active form of CSGKLIC contains an intramolecular disulfide bond
      and maintains a preference for a folded conformation, apparently including a type
      I reverse turn about the residues SGKL. No such preference is observed for the
      reduced form of the peptide, which contains two thiol groups. The presence of the
      disulfide bond is thus integral to the formation of the structure of the loop in
      solution. In agreement with this finding, elimination of the possibility of loop
      formation by substitution of S for C at the amino or carboxy termini of the 7-mer
      is accompanied by the failure of antibody binding to this peptide.

PMID- 2002541
TI  - Adenovirus type 2 VAI RNA transcription by polymerase III is blocked by sequence
      specific methylation.
AB  - Sequence-specific methylation of the promoter and adjacent regions in mammalian
      genes transcribed by RNA polymerase II leads to the inhibition of these genes. So
      far, RNA polymerase III-transcribed genes have not been investigated in depth. We
      therefore studied methylation effects on the RNA polymerase III-transcribed VAI
      gene of adenovirus type 2 DNA. The VAI gene contains 20 5'-CG-3' dinucleotides,
      of which 4 (20%) can be methylated by HpaII (5'-CCGG-3') and HhaI (5'-GCGC-3').
      Three of these 5'-CG-3' sequences are located close to the internal regulatory
      region of the VAI segment. An unmethylated, a 5'-CCGG-3'- and 5'-GCGC-3'
      methylated, and a 5'-CG-3'-methylated pUC18 construct containing the VAI and VAII
      regions were transfected into mammalian cells. In many experiments, an
      inactivating effect of 5'-CCGG-3' and 5'-GCGC-3' DNA methylation on the VAI
      region was not observed. In contrast, methylation of all 20 5'-CG-3' sequences in
      the VAI region by a CpG-specific DNA methyltransferase from Spiroplasma species
      did interfere with VAI transcription. Transcription of the VAI- and VAII- and of
      the VAI-containing constructs was also shown to be inhibited in an in vitro cell
      free transcription system after the constructs had been methylated at the 5'-CCGG
      3' and 5'-GCGC-3' sequences or at all 5'-CG-3' sequences. When an
      oligodeoxyribonucleotide which carried the internal control block A of the VAI
      region was methylated at three 5'-CG-3' sequences, the formation of a complex
      with HeLa nuclear proteins was abrogated. The results presented support the
      notion that the VAI gene transcribed by the DNA-dependent RNA polymerase III is
      also inactivated by methylation of the decisive 5'-CG-3' sequences.

PMID- 2002542
TI  - In vitro suppression of normal human bone marrow progenitor cells by human
      immunodeficiency virus.
AB  - Incubation of normal human nonadherent and T-cell-depleted bone marrow cells with
      HIVIIIB at multiplicities of infection (MOI) ranging from 0.0001:1 to 1:1 reverse
      transcriptase (RT) units resulted in the dose-dependent suppression of the in
      vitro growth of erythroid burst-forming unit (BFU-E), granulocyte-macrophage (CFU
      GM), and T-lymphocyte (CFU-TL) colonies of progenitor cells. Maximum inhibition
      of colony formation was observed at a 1:1 ratio of virus to bone marrow cells. At
      this MOI, BFU-E and CFU-GM colonies were inhibited by 60 to 80%, while CFU-TL
      colonies were totally suppressed. Inhibition of colony formation was also
      observed at an MOI of 0.1:1 but not with further log dilutions of the virus.
      Incubation of the virus with antibody to gp160 resulted in the complete reversal
      of stem cell suppression and the normalization of colony growth in vitro. For BFU
      E and CFU-GM colonies, this reversal was observed with dilutions of antibody up
      to 1:100 and was no longer observed at titers greater than 1:500. The CFU-TL
      colony number normalized at titers between 1:10 and 1:50. Human immunodeficiency
      virus (HIV) also suppressed by 50% the growth of colonies derived from CD34+ stem
      cell fractions. Infection of CD34+ cells and T-cell-depleted, nonadherent cell
      fractions was demonstrated by detection with HIV-specific DNA probe following
      amplification by polymerase chain reaction. The results suggest that HIV can
      directly infect human bone marrow progenitor cells and affect their ability to
      proliferate and give rise to colonies in vitro. The results indicate a direct
      role for the virus in bone marrow suppression and a possible mechanism for the
      cytopenias observed in patients with AIDS.

PMID- 2002543
TI  - Selection, recombination, and G----A hypermutation of human immunodeficiency
      virus type 1 genomes.
AB  - Human immunodeficiency virus type 1 (HIV-1) isolates are genetically so
      heterogeneous that they must be described in terms of populations of related but
      distinct genomes called quasispecies. A recent study of the influence of ex vivo
      culturing on HIV-1 quasispecies demonstrated that usually low-abundance genomes
      outgrew the more prominent forms. Here it is shown that multiple passages of an
      HIV-1 isolate on peripheral blood mononuclear cells resulted in the outgrowth of
      very minor forms. A single passage of equal proportions of supernatants to either
      of the established lymphocyte and monocyte cell lines Molt-3 and U937-2,
      respectively, resulted in the isolation of different sets of minor forms.
      Recombination between component sequences was observed. Extensive and monotonous
      base substitutions of G----A (G----A hypermutation) were evident in many
      sequences. A strong preference for the transition within the GpA dinucleotide was
      observed. Dislocation mutagenesis, in this case, a -1 slippage or dislocation of
      the primer with respect to the template, during DNA synthesis by the HIV-1
      reverse transcriptase would explain this bias. When the consequences of
      polymerase errors, recombination, hypermutation, and instability are added to the
      genetic description of HIV-1, the real complexity of this virus starts to become
      apparent.

PMID- 2002544
TI  - Naturally occurring missense mutation in the polymerase gene terminating
      hepatitis B virus replication.
AB  - A hepatitis B virus (HBV) genome was cloned from human liver. Numerous mutations
      in all viral genes define this HBV DNA as a mutant, divergent from all known HBV
      DNA sequences. Functional analyses of this mutant demonstrated a defect blocking
      viral DNA synthesis. The genetic basis of this defect was identified as a single
      missense mutation in the 5' region of the viral polymerase gene, resulting in the
      inability to package pregenomic RNA into core particles. The replication defect
      could be trans-complemented by a full-length wild-type, but not by a full-length
      mutant or 3'-truncated wild-type, polymerase gene construct. Our findings
      indicate a critical role of the 5' polymerase gene region in the life cycle of
      the virus and suggest that introducing missense mutations in this region can be a
      strategy to terminate viral replication in vivo.

PMID- 2002545
TI  - Selection of genetic variants of simian immunodeficiency virus in persistently
      infected rhesus monkeys.
AB  - Genetic and antigenic variation may be one means by which lentiviruses that cause
      AIDS avoid elimination by host immune responses. Genetic variation in the
      envelope gene (env) was studied by comparing the nucleotide sequences of 27
      clones obtained from two rhesus monkeys infected with molecularly cloned simian
      immunodeficiency virus. All 27 clones differed from each other and differed from
      the input clone in the gp120 (SU) portion of the envelope gene. Nucleotide
      substitutions were shown to accumulate with time at an average rate of 8.5 per
      1,000 per year in SU. Surprisingly, the majority of nucleotide substitutions
      (81%) resulted in amino acid changes. Variation in SU was not random but occurred
      predominantly in five discrete regions. Within these variable regions, a
      remarkable 98% of the nucleotide substitutions changed the amino acid. These
      results demonstrate that extensive sequence variability accumulates in vivo after
      infection with molecularly cloned virus and that selection occurs in vivo for
      changes in distinct variable regions in env.

PMID- 2002546
TI  - Detection of occult simian immunodeficiency virus SIVsmm infection in
      asymptomatic seronegative nonhuman primates and evidence for variation in SIV gag
      sequence between in vivo- and in vitro-propagated virus.
AB  - Polymerase chain reaction techniques were used to identify simian
      immunodeficiency virus (SIV) SIVsmm gag sequences in genomic DNA isolated from
      peripheral blood mononuclear cells from naturally infected asymptomatic
      seropositive and seronegative sooty mangabeys (Cercocebus atys) and from
      experimentally infected but asymptomatic rhesus macaques (Macaca mulatta). The
      results indicate that most if not all SIV-seronegative mangabeys from the colony
      at the Yerkes Primate Center are in fact infected with SIVsmm despite their lack
      of humoral immune response, confirming previous immunological and virological
      observations made by our laboratory. Sequence analysis of these particular gag
      fragments from the mangabey revealed an average of 88% nucleotide sequence
      homology but 97% amino acid identity with the previously published sequence of
      the SIVsmmH4 clone. The significance of this finding relative to the asymptomatic
      state of SIV-infected mangabeys and disease-susceptible SIV-infected rhesus
      macaques is discussed.

PMID- 2002547
TI  - Characterization of immunodominant epitopes of gag and pol gene-encoded proteins
      of human T-cell lymphotropic virus type I.
AB  - A series of synthetic peptides derived from the corresponding regions of the gag,
      pol, and env proteins of human T-cell lymphotropic virus types I (HTLV-I) and II
      (HTLV-II) were used in an enzyme immunoassay to map the immunodominant epitopes
      of HTLV. Serum specimens from 79 of 87 (91%) HTLV-I-infected patients reacted
      with the synthetic peptide Gag-1a (amino acids [a.a.] 102 to 117) derived from
      the C terminus of the p19gag protein of HTLV-I. Minimal cross-reactivity (11%)
      was observed with serum specimens from HTLV-II-infected patients. Peptide Pol-3,
      encoded by the pol region of HTLV-I (a.a. 487 to 502), reacted with serum
      specimens from both HTLV-I- and HTLV-II-infected patients (94 and 86%,
      respectively). The antibody levels to Pol-3 were significantly higher (P less
      than 0.01) in patients with HTLV-I-associated myelopathy/tropical spastic
      paraparesis than in either adult T-cell leukemia patients or HTLV-I-positive
      asymptomatic carriers. None of the other peptides studied demonstrated
      significant binding to serum specimens obtained from HTLV-I- or HTLV-II-infected
      individuals. While Gag-1a did not react with serum specimens from normal
      controls, Pol-3 demonstrated some reaction with specimens from seronegative
      individuals (11.4%). The antibodies to Gag-1a and Pol-3 in serum specimens from
      HTLV-I-infected patients could be specifically inhibited by the corresponding
      synthetic peptides and by a crude HTLV-I antigen preparation, indicating that
      these peptides mimic native epitopes present in HTLV-I proteins that are
      recognized by serum antibodies from HTLV-I- and -II-infected individuals.

PMID- 2002548
TI  - The R-U5-5' leader sequence of neurovirulent wild mouse retrovirus contains an
      element controlling the incubation period of neurodegenerative disease.
AB  - The wild mouse ecotropic retrovirus CasBrE causes a spongiform neurodegenerative
      disease after neonatal inoculation, with an incubation period ranging from 2 to
      12 months. We previously showed that introduction of long terminal repeat (LTR)
      and gag-pol sequences from a strain of Friend murine leukemia virus (FB29)
      resulted in a dramatic acceleration of the onset of the disease. The chimeric
      virus FrCasE, which consisted of the FB29 genome containing 3' pol and env
      sequences from the wild mouse virus, induced a highly predictable, lethal
      neurodegenerative disease with an incubation period of only 16 days. Here we
      report that the sequences which are primary determinants of the length of the
      incubation period are located in the 5' end of the viral genome between a KpnI
      site in the R region of the LTR and a PstI site immediately 5' of the start codon
      for pr65gag (R-U5-5' leader). This region contains the tRNA primer binding site,
      splice donor site for the subgenomic env mRNA, and the packaging sequence.
      Computer-assisted sequence analysis failed to find evidence of a consensus
      sequence for a DNA enhancer in this region. In addition, sequences within a
      region of the genome between a ClaI site at the 3' end of env to the KpnI site in
      the R region of the LTR (inclusive of U3) also influenced the incubation period
      of the disease, but the effect was distinctly weaker than that of the R-U5-5'
      leader sequence. This U3 effect, however, appeared to be independent of the
      number of direct repeats, since deletion of one of two duplicated 42-base repeats
      containing consensus sequences of nuclear-factor binding domains had no effect on
      the incubation period of the disease. On the basis of Southern blot analysis of
      total viral DNA in the tissues, the effect of these sequences on the incubation
      period appeared to be related to the level of virus replication in the central
      nervous system. All of the chimeric viruses analyzed, irrespective of
      neurovirulence, replicated to comparable levels in the spleen and induced
      comparable levels of viremia.

PMID- 2002549
TI  - Determination of viral proteins present in the human immunodeficiency virus type
      1 preintegration complex.
AB  - Cytoplasmic extracts prepared from cells infected with metabolically radiolabeled
      virions of human immunodeficiency virus type 1 contain viral DNA in association
      with labeled viral proteins. Viral DNA can be purified from these extracts by gel
      filtration chromatography and sucrose gradient sedimentation as a part of a
      nucleoprotein complex containing integrase as the only viral protein detectable
      by immunoprecipitation and gel electrophoretic analysis. The purified complex
      contains no detectable gag gene products, including p17, p24, p7, or p6, and
      contains no additional pol gene products, including the p10 protease, p66 and p51
      polymerase, or the p15 RNase H. Nearly all of the purified nucleoprotein
      complexes are capable of integrating into heterologous DNA targets in vitro.
      These observations demonstrate that integrase is a component of the human
      immunodeficiency virus type 1 preintegration complex and suggest that integrase
      may be the only viral protein necessary for the integration of retroviral DNA.

PMID- 2002550
TI  - Chromosomal locations and gonadal dependence of genes that mediate resistance to
      ectromelia (mousepox) virus-induced mortality.
AB  - Four genetic loci were tested for linkage with loci that control genetic
      resistance to lethal ectromelia virus infection in mice. Three of the loci were
      selected because of concordance with genotypes assigned to recombinant inbred
      (RI) strains of mice derived from resistant C57BL/6 and susceptible DBA/2 (BXD)
      mice on the basis of their responses to challenge infection. Thirty-six of 167
      male (C57BL/6 x DBA/2)F1 x DBA/2 backcross (BC) mice died (22%), of which 27
      (75%) were homozygous for DBA/2 alleles at Hc and H-2D. Twenty-eight percent of
      sham-castrated and 6% of sham-ovariectomized BC mice were susceptible to lethal
      mousepox, whereas 50% of gonadectomized mice were susceptible. There was no
      linkage evident between Hc or H-2D and loci that controlled resistance to lethal
      ectromelia virus infection in 44 castrated BC mice. Mortality among female mice
      of BXD RI strains with susceptible or intermediate male phenotypes was strongly
      correlated (r = 0.834) with male mortality. Gonadectomized C57BL/6 mice were as
      resistant as intact mice to lethal ectromelia virus infection. These results
      indicate that two gonad-dependent genes on chromosomes 2 and 17 and one gonad
      independent gene control resistance to mousepox virus infection, that males and
      females share gonad-dependent genes, and that the gonad-independent gene is fully
      protective.

PMID- 2002551
TI  - Mammalian reoviruses contain a myristoylated structural protein.
AB  - The structural protein mu 1 of mammalian reoviruses was noted to have a potential
      N-myristoylation sequence at the amino terminus of its deduced amino acid
      sequence. Virions labeled with [3H]myristic acid were used to demonstrate that mu
      1 is modified by an amide-linked myristoyl group. A myristoylated peptide having
      a relative molecular weight (Mr) of approximately 4,000 was also shown to be a
      structural component of virions and was concluded to represent the 4.2-kDa amino
      terminal fragment of mu 1 which is generated by the same proteolytic cleavage
      that yields the carboxy-terminal fragment and major outer capsid protein mu 1C.
      The myristoylated 4,000-Mr peptide was found to be present in reovirus
      intermediate subviral particles but to be absent from cores, indicating that it
      is a component of the outer capsid. A distinct large myristoylated fragment of
      the intact mu 1 protein was also identified in intermediate subviral particles,
      but no myristoylated mu-region proteins were identified in cores, consistent with
      the location of mu 1 in the outer capsid. Similarities between amino-terminal
      regions of the reovirus mu 1 protein and the poliovirus capsid polyprotein were
      noted. By analogy with other viruses that contain N-myristoylated structural
      proteins (particularly picornaviruses), we suggest that the myristoyl group
      attached to mu 1 and its amino-terminal fragments has an essential role in the
      assembly and structure of the reovirus outer capsid and in the process of
      reovirus entry into cells.

PMID- 2002552
TI  - Phenotypic heterogeneity in a panel of infectious molecular human
      immunodeficiency virus type 1 clones derived from a single individual.
AB  - Previously, we and others have demonstrated a relation between the clinical
      course of human immunodeficiency virus type 1 (HIV-1) infection and biological
      properties of HIV-1 variants such as replication rate, syncytium-inducing (SI)
      capacity, and cytotropism. For the molecular analysis of the biological
      variability in these properties, we generated a panel of phenotypically distinct
      yet genetically highly homologous infectious molecular clones. These clones were
      derived from HIV-1 isolates, mostly recovered by direct clonal isolation, from a
      single individual in whom a transition from non-SI to SI isolates had been
      identified over time. Of 17 molecular clones tested, 8 were infectious. The
      clones exhibited differences in SI capacity and T-cell line tropism. Their
      phenotypes corresponded to those of their parental isolates, formally
      demonstrating that biological variability of HIV-1 isolates can be attributed to
      single molecular clones. With these clones we demonstrated that SI capacity and
      tropism for the H9 T-cell line, almost invariably coupled in primary HIV-1
      isolates, are discernible properties. Also different requirements appeared to
      exist for H9 and Sup T1 cell line tropism. We obtained evidence that T-cell line
      tropism is not caused by differences in level of HIV-1 expression but most
      probably is restricted at the level of virus entry. Restriction mapping of four
      clones with divergent phenotypes revealed a high degree of nucleotide sequence
      homology (over 96.3%), indicating the usefulness of these clones for the tracking
      of genetic variability critical for differences in biological phenotype.

PMID- 2002553
TI  - Absent or rare human immunodeficiency virus infection of bone marrow
      stem/progenitor cells in vivo.
AB  - An important question in human immunodeficiency virus (HIV) pathogenesis is
      whether HIV-infected bone marrow CD34+ stem/progenitor cells serve as a
      significant reservoir of virus in HIV-infected individuals. Our data indicate
      that infection of bone marrow stem/progenitor cells with HIV occurs rarely, if
      ever, in vivo. In the present study, CD34+ cells were immunomagnetically purified
      from the bone marrow of HIV-seropositive individuals, and purified cells or
      colony-forming cells of the granulocyte/macrophage lineage were analyzed for HIV
      proviral DNA by the polymerase chain reaction. No HIV DNA was detected in colony
      forming cells of the granulocyte/macrophage lineage from HIV-positive patients.
      Furthermore, no virus was found in CD34(+)-enriched cells from six of seven
      samples from asymptomatic HIV-infected individuals and four of four samples from
      patients with AIDS-related complex or AIDS. Thus, infected stem cells are not a
      major source of persistent HIV and do not account for hematopoietic suppression.
      These findings have positive implications for the concept of marrow
      reconstitution with autologous stem cells, genetically engineered for HIV
      resistance, following marrow-ablative antiviral therapy.

PMID- 2002554
TI  - Defective retroviruses can disperse in the human genome by intracellular
      transposition.
AB  - Using an assay for retrotransposition detection (T. Heidmann, O. Heidmann, and J.
      F. Nicolas, Proc. Natl. Acad. Sci. USA 85:2219-2223, 1988), we demonstrated that
      a defective retrovirus deleted for the gag, pol, and env open reading frames can
      disperse in the genome of human HeLa cells by intracellular transposition, at a
      frequency close to 10(-6) events per cell per generation. Transposition requires
      cooperation in trans for the gag and pol gene products and may be associated with
      the release of low amounts of noninfectious retroviruslike particles which are
      the hallmarks but not the intermediates of this transposition process. Similar
      events could account for the dispersion at high copy number of some of the human
      endogenous sequences related to retroviruses and for the occurrence of
      noninfectious retroviruslike particles in human placenta and several tumor cell
      lines (reviewed by E. Larsson, N. Kato, and M. Cohen, Curr. Top. Microbiol,
      Immunol, 148:115-132, 1989).

PMID- 2002555
TI  - Human immunodeficiency virus type 1 gp120 envelope glycoprotein regions important
      for association with the gp41 transmembrane glycoprotein.
AB  - Insertion of four amino acids into various locations within the amino-terminal
      halves of the human immunodeficiency virus type 1 gp120 or gp41 envelope
      glycoprotein disrupts the noncovalent association of these two envelope subunits
      (M. Kowalski, J. Potz, L. Basiripour, T. Dorfman, W. C. Goh, E. Terwilliger, A.
      Dayton, C. Rosen, W. A. Haseltine, and J. Sodroski, Science 237:1351-1355, 1987).
      To localize the determinants on the gp120 envelope glycoprotein important for
      subunit association, amino acids conserved among primate immunodeficiency viruses
      were changed. Substitution mutations affecting either of two highly conserved
      regions located at the amino (residues 36 to 45) and carboxyl (residues 491 to
      501) ends of the mature gp120 molecule resulted in nearly complete dissociation
      of the envelope glycoprotein subunits. Partial dissociation phenotypes were
      observed for some changes affecting residues in the third and fourth conserved
      gp120 regions. These results suggest that hydrophobic regions at both ends of the
      gp120 glycoprotein contribute to noncovalent association with the gp41
      transmembrane glycoprotein.

PMID- 2002556
TI  - Minimal Rev-response element for type 1 human immunodeficiency virus.
AB  - Rev protein regulates nuclear export of viral mRNAs that contain a 240-base RNA
      sequence termed the Rev-response element (RRE). We demonstrate that an 88-base
      truncated RRE encompassing a known Rev binding site can mediate Rev
      responsiveness in vivo. Two tandem copies of this mutant function as efficiently
      as the full-length RRE.

PMID- 2002557
TI  - Mutational analysis of the carboxyl terminus of the Moloney murine leukemia virus
      integration protein.
AB  - The integration protein (IN) is required for retrovirus DNA integration into the
      host DNA. The function of the C terminus of the Moloney murine leukemia virus IN
      protein was examined. The terminal 28 amino acids were found to be nonessential.
      A linker insertion at position 6025, within a 36-amino-acid insertion not found
      in any other retrovirus, also produced viable virus.

PMID- 2002558
TI  - Immunoglobulin A mediation of murine nasal anti-influenza virus immunity.
AB  - Most mice which have recovered from influenza virus infection are immune to
      reinfection with the same influenza virus. This immunity could be abrogated by
      the intranasal instillation of anti-immunoglobulin A (anti-IgA) but not of anti
      IgG or anti-IgM antiserum. Thus, IgA is the major, if not the sole, mediator of
      nasal immunity to influenza virus in immunocompetent mice.

PMID- 2002559
TI  - AUA Eighty-Sixth Annual Meeting. American Urological Association. June 2-6, 1991,
      Toronto, Canada.

PMID- 2002560
TI  - Desert Storm: wounded Iraqi war prisoners keep US physicians busy.

PMID- 2002561
TI  - As data on antiprogesterone compounds grow, societal and scientific aspects are
      scrutinized.

PMID- 2002562
TI  - A piece of my mind. Healing arts.

PMID- 2002563
TI  - Pneumocystis carinii as foamy exudate in bone marrow.

PMID- 2002564
TI  - The HIV testing policies of US hospitals.

PMID- 2002565
TI  - Inoculating blood cultures: recapping needles and contamination rates.

PMID- 2002566
TI  - Life and death in the US Army.

PMID- 2002567
TI  - The prevention of war.

PMID- 2002568
TI  - Prevention of bacterial endocarditis.

PMID- 2002569
TI  - Pressure ulcers.

PMID- 2002570
TI  - Lowering lipids improves coronary arterial anatomy.

PMID- 2002571
TI  - Prevalence of HIV infection in childbearing women in the United States.
      Surveillance using newborn blood samples.
AB  - A national, population-based survey was initiated in 1988 to measure the
      prevalence of human immunodeficiency virus (HIV) infection in women giving birth
      to infants in the United States. Following standardized procedures, residual
      dried-blood specimens collected on filter paper for newborn metabolic screening
      were tested anonymously in state public health laboratories for maternal antibody
      to HIV. As of September 1990, annual survey data were available from 38 states
      and the District of Columbia. The highest HIV seroprevalence rates were observed
      in New York (5.8 per 1000), the District of Columbia (5.5 per 1000), New Jersey
      (4.9 per 1000), and Florida (4.5 per 1000). Nationwide, an estimated 1.5 per 1000
      women giving birth to infants in 1989 were infected with HIV. Assuming a
      perinatal transmission rate of 30%, we estimate that approximately 1800 newborns
      acquired HIV infection during one 12-month period. Preventing transmission of HIV
      infection to women and infants is an urgent public health priority.

PMID- 2002572
TI  - Trends of HIV seroconversion among young adults in the US Army, 1985 to 1989. US
      Army Retrovirus Research Group.
AB  - Because soldiers in the US Army are recurrently tested for the presence of
      antibody to the human immunodeficiency virus (HIV), HIV seroconversion rates can
      be directly measured. From November 1985 through October 1989, 429 HIV
      seroconversions were detected among 718,780 soldiers who contributed 1,088,447
      person-years of follow-up time (HIV seroconversion rate, 0.39 per 1000 person
      years). Period-specific seroconversion rates declined significantly from 0.49 per
      1000 person-years (November 1985 through October 1987) to 0.33 per 1000 person
      years (November 1987 through October 1988) to 0.29 per 1000 person-years
      (November 1988 through October 1989). The HIV seroconversion risk among active
      duty soldiers was significantly associated with race/ethnic group, age, gender,
      and marital status. Based on these trends, we estimate that approximately 220
      soldiers (95% confidence interval, 160 to 297 soldiers) were infected with HIV
      during 1989 and 1990, with potentially fewer in future years.

PMID- 2002573
TI  - The epidemiology of tuberculosis among North Carolina migrant farm workers.
AB  - Although tuberculosis (TB) has been recognized as a significant health problem of
      migrant farm workers, the nature and extent of the problem have been poorly
      defined. We report the first population-based study of TB in a random sample of
      farm workers (n = 543) and the first use of recall antigens in an epidemiologic
      study of TB. Purified protein derivative positivity ranged from 33% in Hispanics
      to 54% in US-born blacks and 76% in Haitians. Active tubercular disease occurred
      in 3.6% of US-born blacks and 0.47% of Hispanics. Among US-born blacks, risk
      factors associated with farm work were most significant. Blacks born in the
      United States also had the highest prevalence of anergy. The use of recall
      antigens made possible a better description of the epidemiology of TB by
      excluding false negatives and clarifying associations between infection and risk
      factors. We conclude that TB among farm workers represents a serious public
      health problem with previously unrecognized risk factors. Additional resources
      for migrant health care, improvements in health care access, and fundamental
      changes in the system of migrant labor are all necessary to reduce the
      transmission of TB.

PMID- 2002574
TI  - Coronary thrombolysis for the elderly?

PMID- 2002575
TI  - Economic barriers to the use of oral rehydration therapy. A case report.
AB  - Diarrheal dehydration is a highly prevalent condition among young children and is
      readily prevented and treated with oral rehydration therapy. We report a death
      due to hypernatremic dehydration caused by rotavirus diarrhea of a 9-month-old
      infant whose mother attempted to purchase oral glucose-electrolyte solution in a
      pharmacy but was unable to afford it. While efforts such as the National ORT
      Project should help to promote the proper at-home treatment of this condition, we
      conclude that oral rehydration therapy will not be used optimally by the parents
      of children living in poverty until the economic barriers to its use are removed.

PMID- 2002576
TI  - Ultrasonic imaging of the abdomen. Report of the ultrasonography task force.
      Council on Scientific Affairs, American Medical Association.
AB  - As new imaging modalities emerge and existing technologies improve, indications
      for a particular imaging method may change. This article examines current
      indications for abdominal and prostatic ultrasound examination and, where
      possible, compares ultrasound with other imaging techniques. This is not an
      attempt to list all possible ultrasound indications or examinations, but rather
      an attempt to serve as an aid to informed imaging selection based on current
      literature and equipment.

PMID- 2002577
TI  - Tuberculosis and migrant farm workers.

PMID- 2002578
TI  - Food allergy and irritable bowel syndrome.

PMID- 2002579
TI  - Elective appendectomy during abdominal surgery.

PMID- 2002580
TI  - Tourette's syndrome.

PMID- 2002581
TI  - Risks of HIV exposure.

PMID- 2002582
TI  - Learning from the Cruzan decision: the need for advance directives.

PMID- 2002583
TI  - Placebo effects on mind and body.

PMID- 2002584
TI  - Dog lab: a question of rite and wrong.

PMID- 2002585
TI  - AMA-RPS instrumental in achieving new maternity leave policy.

PMID- 2002586
TI  - [Hypertrophic cardiomyopathy: pressure gradient and obstruction].

PMID- 2002587
TI  - [Ultrafast CT for diagnosis of cardiomyopathy].

PMID- 2002588
TI  - [Evaluation of cardiomyopathies using cine MRI].

PMID- 2002589
TI  - [Cardiac blood-pool imaging and functional images].

PMID- 2002590
TI  - [Myocardial imaging with 123I-MIBG and 201Tl].

PMID- 2002591
TI  - [111In-antimyosin Fab myocardial scintigraphy].

PMID- 2002592
TI  - [Myocardial blood flow imaging of cardiomyopathy with N-13 ammonia].

PMID- 2002593
TI  - [Evaluation of myocardial glucose utilization of hypertrophic and dilated
      cardiomyopathy using 18F-2-fluoro 2-deoxy-D-glucose and positron emission
      tomography].

PMID- 2002594
TI  - [Myocardial fatty acid metabolic imaging using C-11 labeled palmitate].

PMID- 2002595
TI  - [The prognosis of cardiomyopathy].

PMID- 2002596
TI  - [Dilated cardiomyopathy].

PMID- 2002597
TI  - [Calcium antagonists in cardiomyopathy].

PMID- 2002598
TI  - [Viral myocarditis].

PMID- 2002599
TI  - [Diabetic cardiomyopathy: microangiopathy and myocardiac cellular damage].

PMID- 2002600
TI  - [Total abstinence and alcoholic cardiomyopathy].

PMID- 2002601
TI  - [Hereditary heart muscle diseases].

PMID- 2002602
TI  - [Electrophysiological studies in idiopathic cardiomyopathy].

PMID- 2002603
TI  - [Mitochondrial DNA mutations and cardiomyopathy].

PMID- 2002604
TI  - [Contractility and energetics in cardiac hypertrophy].

PMID- 2002605
TI  - [The animal model of cardiomyopathy].

PMID- 2002606
TI  - [Molecular mechanisms of oncogene activation in hematological malignancies].

PMID- 2002607
TI  - [Relation of electrocardiographic features and distribution of hypertrophy in
      hypertrophic cardiomyopathy].

PMID- 2002608
TI  - [Hypertrophic cardiomyopathy].

PMID- 2002609
TI  - [Dilated cardiomyopathy].

PMID- 2002610
TI  - [Definition, classification and pathogenesis of cardiomyopathies--recent
      development].

PMID- 2002611
TI  - [Restrictive cardiomyopathy].

PMID- 2002612
TI  - [Apical hypertrophic cardiomyopathy].

PMID- 2002613
TI  - [A proposal on the existence of electric disturbance type of cardiomyopathy
      (ECM)].

PMID- 2002614
TI  - [Various clinical profiles of hypertrophic cardiomyopathy].

PMID- 2002616
TI  - [77th Annual Meeting of the Japanese Society of Gastroenterology. March 28, 29,
      30, 1991, Tokyo. Abstracts].

PMID- 2002615
TI  - [Echocardiographic and Doppler echocardiographic findings of cardiomyopathy].

PMID- 2002617
TI  - Kindred spirits.

PMID- 2002618
TI  - Adult respiratory distress syndrome in early-stage pneumonia.

PMID- 2002619
TI  - Lobbying, Kansas style.

PMID- 2002620
TI  - Point of view.

PMID- 2002621
TI  - The National Practitioner Data Bank.

PMID- 2002622
TI  - Your computer and you.

PMID- 2002623
TI  - Summary: symposium on optical methods applicable to renal research.

PMID- 2002624
TI  - Glomerular interleukin 1 production is dependent on macrophage infiltration in
      anti-GBM glomerulonephritis.
AB  - Both macrophages and glomerular mesangial cells have the potential to synthesize
      interleukin 1 (IL-1), however, their respective contributions to IL-1 production
      in anti-GBM glomerulonephritis (GN) are unknown. To address this problem, IL-1
      production by glomeruli from rabbits with macrophage-associated anti-GBM GN
      (passive autologous anti-GBM GN [PAGBMGN]) and macrophage independent
      (heterologous phase) anti-GBM GN was studied. Macrophage-infiltrated nephritic
      glomeruli produced IL-1 bioactivity which was inhibitable by an anti-IL-1
      antibody, and had a molecular weight consistent with rabbit IL-1. Glomerular IL-1
      production in PAGBMGN was markedly augmented (1.43 +/- 0.79 U/10(3) glomeruli
      [gloms]/24 hr) compared to normal glomeruli (0.13 +/- 0.06 U/10(3) gloms/24 hr, P
      less than 0.05) or glomeruli from rabbits with macrophage independent GN (0.11 +/
      0.07 U/10(3) gloms/24 hr, P less than 0.05). IL-1 production by glomeruli from
      leukocyte depleted rabbits with PAGBMGN (0.16 +/- 0.07 U/10(3) gloms/24 hr) was
      not significantly elevated compared to normal glomeruli. Glomerular macrophages
      from rabbits with PAGBMGN produced more IL-1 (3.62 +/- 1.63 U/10(3) cells/24 hr)
      than blood monocytes (0.51 +/- 0.30 U/10(3) cells/24 hr) or alveolar macrophages
      (0.24 +/- 0.12 U/10(3) cells/24 hr) from the same animals. These results show
      that in experimental anti-GBM GN where injury is macrophage dependent, IL-1
      production is also macrophage dependent and infiltrating glomerular macrophages
      are the major source of IL-1. Further, as glomerular IL-1 production was not
      significantly augmented in GN in the absence of macrophages, glomerular
      deposition of immunoglobulin and complement alone do not stimulate significant IL
      1 production by intrinsic glomerular cells in experimental anti-GBM GN.

PMID- 2002625
TI  - Myoglobin depletes renal adenine nucleotide pools in the presence and absence of
      shock.
AB  - To assess whether myoglobin adversely affects renal adenylate pools, rats were
      infused with purified myoglobin (50 mg/100 g body wt) for two hours and renal
      ATP, ADP, and AMP levels were measured in the absence of shock, after 25 minutes
      of hemorrhagic shock (55 to 60 mm Hg) or 30 minutes post-recovery. In the absence
      of shock, myoglobin lowered ATP by 24% (assessed 65 min post-infusion) without
      affecting renal blood flow (RBF). This effect was completely blocked by
      deferoxamine (DFO) treatment and it could not be reproduced by ribonuclease
      infusion (a non-Fe containing, but filtered, protein). Myoglobin + shock caused a
      three- to fourfold greater decline in ATP than did shock alone despite comparable
      RBFs. Shock plus myoglobin, but neither one alone, induced substantial S1/S2
      proximal tubular morphologic damage and a severe reduction in creatinine
      clearance, confirming synergistic injury. Ribonuclease completely reproduced
      myoglobin's effect on shock-induced adenylate profiles. DFO +/- hydroxyl radical
      scavenger therapy (Na benzoate) did not block the myoglobin shock effect on
      adenylate pools. Post-shock adenylate recovery was not compromised by myoglobin
      pre-treatment. If renal artery occlusion (RAO), rather than shock, was used as
      the ischemic challenge, myoglobin had no discernible impact on adenine nucleotide
      content. This study concludes that: 1) myoglobin modestly lowers baseline
      adenylate pools due to an Fe dependent mechanism; 2) myoglobin drastically
      accentuates shock-induced adenylate depletion by a non-hemodynamic/non-Fe
      dependent mechanism; 3) myoglobin nephrotoxicity cannot be attributed solely to
      tissue iron loading; and 4) the RAO model can completely mask important
      influences on ischemic cellular energetics.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2002626
TI  - Renal functional adaptation of the adult kidney following transplantation to the
      child.
AB  - Nineteen child renal transplant recipients, aged 1.3 to 19.2 years at
      transplantation, and their adult living-related kidney donors, 27 to 60 years of
      age at nephrectomy, were investigated simultaneously with regard to renal
      function. At a median time of three months after transplantation clearances of
      inulin (GFR) and paraaminohippuric acid (ERPF) were measured, and serum urea and
      creatinine concentrations were determined. The absolute values for GFR (72 +/- 13
      ml/min) and ERPF (369 +/- 76 ml/min) in the donors were significantly higher than
      those of the recipients (37 +/- 22 and 196 +/- 72 ml/min, respectively). The
      absolute values of GFR and ERPF were significantly correlated with the body
      surface areas of the recipients. Thus, in relation to body surface area, the GFR,
      68 +/- 11 ml/min/1.73 m2, and ERPF, 348 +/- 65 ml/min/1.73 m2, of the donors did
      not differ from those of the recipients, 68 +/- 20 and 375 +/- 90 ml/min/1.73 m2,
      respectively. Because of the greater body mass, the serum creatinine
      concentrations of the donors were significantly higher than those of the
      recipients, whereas the serum urea concentrations were significantly higher in
      the recipients. The results suggest that transplantation of an adult kidney to a
      child results in a functional adaptation to the smaller body size of the
      recipient, and that this adaptation occurs within three months after
      transplantation.

PMID- 2002627
TI  - Red cell Na+/Li+ countertransport in non-insulin-dependent diabetics with
      diabetic nephropathy.
AB  - Genetic predisposition to essential hypertension, as indicated by increased
      maximal velocity of Na+/Li+ countertransport in red cells, has been suggested as
      a marker for the risk of developing diabetic nephropathy. To evaluate the
      validity of this concept in non-insulin-dependent diabetics, we measured the
      maximal velocity of Na+/Li+ countertransport in red cells in 18 male diabetics
      suffering from proteinuria due to biopsy proven diabetic glomerulosclerosis (GFR:
      51 [range 27 to 146] ml/min/1.73 m2), 17 male diabetics with normoalbuminuria,
      and in 18 sex-, age-, and body mass index-matched healthy control subjects.
      Na+/Li+ countertransport was identical in patients with and without diabetic
      nephropathy, 0.43 (0.24 to 0.92) versus 0.44 (0.20 to 0.83) mmol/(liter cells x
      hr), but was elevated compared to control subjects, 0.32 (0.09 to 0.73; P less
      than 0.05). Arterial blood pressure was elevated in patients with nephropathy
      (162/92 +/- 21/9 mm Hg) compared to normoalbuminuric patients (132/82 +/- 15/7)
      and control subjects (133/83 +/- 14/7 mm Hg; P less than 0.001). Our study does
      not support the hypothesis that the risk of diabetic nephropathy in non-insulin
      dependent diabetes is associated with a genetic predisposition to hypertension.
      Diabetes per se seems to enhance Na+/Li+ countertransport activity.

PMID- 2002628
TI  - Glycolate determination detects type I primary hyperoxaluria in dialysis
      patients.
AB  - The detection of type I primary hyperoxaluria is based on the finding of
      exceedingly high oxalate excretion which is associated with increased glycolate
      excretion. The differential diagnosis of this disease may become a difficult task
      once end-stage renal disease (ESRD) and anuria have supervened. The various
      procedures thus far proposed to obviate this circumstance are complex, inaccurate
      or not reproducible. In this paper we propose the accurate liquid chromatographic
      determination of glycolate in blood and dialysate as a means to detect type I
      primary hyperoxaluria in patients on maintenance hemodialysis (RDT). The method
      is based on the enzymatic conversion of glycolate to glyoxylate coupled with
      alpha-keto acid derivatization with phenylhydrazine. The resulting
      phenylhydrazone is then resolved by high-performance liquid chromatograph (HPLC).
      With this method, plasma glycolate in 12 healthy controls was 7.8 +/- 1.7
      mumol/liter, almost twentyfold less than previously reported. Five dialysis
      patients with high serum oxalate, of whom four with primary hyperoxaluria and one
      with Crohn's disease and presumed enteric oxalate hyperabsorption, were checked
      by this method and compared to nine patients with oxalosis-unrelated ESRD. The
      patients with hyperoxalemia were also evaluated for their response to pyridoxine
      therapy. The measurement of glycolate in blood drawn prior to and at the end of
      the dialysis session as well as in the dialysate soundly discriminated the
      patients with type I hyperoxaluria from all the other dialysis patients.
      Glycolate measurement was shown to be much more powerful than oxalate in that
      patients with oxalosis-induced ESRD exhibited an almost two hundred and fiftyfold
      increase compared to the oxalosis-unrelated patients.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 2002629
TI  - rHuEPO treatment improves brain and cognitive function of anemic dialysis
      patients.
AB  - Twenty-four patients with chronic renal failure, stabilized on hemodialysis, were
      treated with recombinant human erythropoietin. Before treatment, all patients
      were anemic (mean Hct = 23.7%). Hematocrits reached normal levels (36.5%) after
      three months of treatment. Brain event-related potentials and neuropsychological
      tests were used to assess changes in brain and cognitive functions associated
      with the correction of anemia. Assessments were done prior to and after three and
      twelve months of rHuEPO treatment. The P3 component of the event-related
      potential increased in amplitude significantly with treatment, while its latency
      was unaffected. Of the four neuropsychological tests administered, scores on two
      improved significantly with treatment, and the other two approached significance.
      Taken together, these findings suggest that the correction of anemia to
      hematocrits near normal in uremic patients by rHuEPO treatment improves brain and
      cognitive function by raising levels of sustained attention, thus increasing
      speed and efficiency of scanning and perceptual-motor functions and enhancing
      learning and memory. These findings also suggest that anemia, either directly or
      indirectly, may impair brain function.

PMID- 2002631
TI  - Hellenic Society of Nephrology. Ioannina, Greece, May 22-25, 1990. Abstracts.

PMID- 2002630
TI  - Lipid abnormalities in renal disease.

PMID- 2002632
TI  - 9th annual meeting of the Korean Society of Nephrology. Seoul, Korea, May 26-27,
      1989. Abstracts.

PMID- 2002633
TI  - Epidermal growth factor (EGF) expression in the congenital polycystic mouse
      kidney.
AB  - The mechanisms responsible for renal cyst formation in congenital polycystic
      kidney disease remain unknown, although abnormalities of cellular metabolism,
      basement membrane components, and growth factors have been suggested. In the
      present study, we examined a potential role for epidermal growth factor (EGF) in
      cyst formation in a mouse model. We measured growth factor activity and
      concentration in renal cyst fluid, urine, and serum obtained from mice with
      congenital polycystic kidney disease (cpk). In affected mice, both growth factor
      activity of urine and the urinary EGF concentration were much lower than
      unaffected littermate controls even when corrected for creatinine concentration.
      Although the growth factor activity was much lower in affected mice, there were
      significant differences in the regional distribution of EGF in animals with
      cysts. Both growth factor activity and EGF concentration were greater in cyst
      fluid when compared to urine. Growth factor activity in cysts was completely
      inhibited by anti-EGF antibody using BALB/MK epithelial keratinocytes as targets.
      The expression of EGF mRNA in kidneys from affected mice was markedly decreased
      when compared to littermate controls. These results suggest that decreased EGF
      production and local differences in EGF concentration may contribute to cyst
      formation.

PMID- 2002634
TI  - Renal nerves and the natriuresis following unilateral renal exclusion in the rat.
AB  - Both acute unilateral nephrectomy (AUN) and acute ureteral pressure elevation
      (UPE) stimulate sodium excretion (UNaV) from the contralateral kidney, a response
      which in each case is interrupted by prior denervation of either kidney. Yet the
      natriuresis after AUN is known to be related to an increase in the plasma
      concentration of a gamma-melanocyte stimulating hormone (gamma-MSH)-like peptide.
      In anesthetized rats, sham AUN had no effect on contralateral UNaV, and plasma
      immunoreactive (IR) gamma-MSH concentration was 10.6 +/- 3.0 (SD) fmol/ml. In
      rats with intact renal innervation, UNaV more than doubled after AUN (P less than
      0.001), and IR-gamma-MSH was increased to 14.9 +/- 4.6 fmol/ml (P less than
      0.025). Unilateral renal denervation led to the expected increase in ipsilateral
      and decrease in contralateral UNaV, and neither sham AUN nor AUN of the
      denervated of innervated kidney influenced UNaV. In all three of these groups, IR
      gamma-MSH concentration was reduced below the sham or post-AUN values seen in
      rats with innervated kidneys, to 4.9 +/- 3.3, 3.8 +/- 3.4, and 2.8 +/- 3.5
      fmol/ml, respectively (P less than 0.001 for all). These results suggested that
      removal of renal afferent nerve input by renal denervation lowered basal IR-gamma
      MSH activity and prevented the stimulated level normally seen after AUN. To
      examine the effect of stimulating afferent renal nerve activity, we carried out
      UPE, a maneuver known to increase ipsilateral afferent renal nerve traffic
      through activation of renal mechanoreceptors, as well as cause a natriuresis from
      the contralateral kidney.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2002635
TI  - Antigen processing and presentation by glomerular visceral epithelium in vitro.
AB  - Although macrophages are considered the prototype of antigen presenting cells
      (APC), recent studies have emphasized the potential role of several parenchymal
      and mesenchymal cells in this process. We have studied the capacity of cultured
      glomerular visceral epithelial cells (GEC) to act as effective APC and compared
      this capacity with that demonstrated by peritoneal macrophages. Affinity-purified
      and in vitro propagated rat GEC were exposed to hen egg lysozyme, keyhole limpet
      hemocyanin, and cationic ferritin. As effector cells, we used antigen-specific T
      cell hybridomas; the level of antigen presentation was assessed by determining
      the level of interleukin 2 (IL-2) present in tissue culture supernatants.
      Cytokine-treated GEC were capable of processing and presenting all antigens in a
      dose-dependent manner. Crucial for antigen presentation were intracellular
      processing of antigen and the presence of Ia on the cell surface. Our findings
      indicate that GEC can act as effective APC, and further suggest that this
      capacity may be relevant to cell-mediated immune injury at the level of the
      glomerular capillaries in vivo.

PMID- 2002636
TI  - Effect of chlorpropamide on water and urea transport in the inner medullary
      collecting duct.
AB  - The present in vitro microperfusion study examined whether chlorpropamide (CPM)
      has a direct effect on hydraulic conductivity (Lp x 10(-6) cm/atm.sec) and 14C
      urea permeability (Pu x 10(-5) cm/sec) in the middle and distal inner medullary
      collecting duct (IMCD) obtained from acutely water-loaded Wistar rats and rats
      homozygous for diabetes insipidus (DI). CPM (10(-4) M) added to the bath fluid
      increased the Lp in the water-loaded Wistar rats from -0.05 +/- 0.13 to 6.25 +/-
      0.74 (p less than 0.01) and in the DI rats from 0.05 +/- 0.01 to 5.95 +/- 0.84 (p
      less than 0.01), but had no effect when it was added to the perfusate. CPM
      stimulated Lp in a dose-dependent manner with the threshold effect at 10(-6) M.
      However, the addition of CPM (10(-4) M) to submaximal concentration of VP in the
      bath fluid did not increase the Lp. Furthermore, CPM was unable to block the
      inhibitory action of PGE2 on the vasopressin (VP)-stimulated Lp. On the contrary,
      PGE2 blocked the CPM-stimulated Lp. CPM (10(-4) M) in the peritubular fluid was
      able to cause a significant rise of the Pu from 13.5 +/- 0.8 to 17.3 +/- 1.0
      reversibly, which represented 16% of maximum stimulated effect produced by 50
      microU/ml of VP. Thus, pharmacological doses of CPM added to the peritubular side
      have a direct effect on terminal IMCD increasing water and urea permeability in
      the absence of VP, but this drug does not potentiate the VP-stimulated water
      transport in the IMCD. Our results were unable to confirm the hypothesis that CPM
      potentiates the VP-antidiuresis by the inhibition of PGE2 action in the rat IMCD.

PMID- 2002637
TI  - Dialysis hypotension: a hemodynamic analysis.

PMID- 2002638
TI  - Localization of clusterin in the epimembranous deposits of passive Heymann
      nephritis.
AB  - The membrane attack complex of complement (MAC) plays an important role in the
      mediation of proteinuria in experimental membranous nephropathy induced by
      Heymann antiserum. SP-40,40 is a recently described serum protein which appears
      to inhibit the formation of cytolytic MAC in a manner analogous to S
      protein/vitronectin. SP-40,40 is homologous to proteins originally isolated from
      rat and ram seminal fluid (sulfated glycoprotein 2 and clusterin, respectively).
      By current convention, these proteins are considered clusterin homologues. The
      objective of this study was to examine the participation of rat clusterin in
      passive Heymann nephritis. Using an antibody to rat clusterin as an
      immunofluorescent probe, clusterin deposits were demonstrated along the
      glomerular capillary wall in an identical pattern to rat C3 and C5b-9.
      Decomplementation using cobra venom factor prevented proteinuria and
      intraglomerular MAC formation. The epimembranous clusterin were not detected in
      the complement-depleted animals. The role of clusterin in the mediation of
      glomerular injury remains unknown, but it is probably related to in situ
      formation of the terminal complement cascade where it may play a regulatory role.

PMID- 2002639
TI  - The effect of dopamine receptor blockade on natriuresis is dependent on the
      degree of hypervolemia.
AB  - A number of different physiological factors and systems have been suggested to be
      responsible for the natriuretic effect following acute isotonic volume expansion
      (VE). The variation in suggestions may depend on the prevailing status of the
      systems governing fluid and electrolyte balance before VE, on the expansion
      medium and on the rate and degree of VE. A study was performed to determine
      whether the previously documented attenuating effect of dopamine receptor
      blockade on natriuresis induced by VE is dependent on the degree of hypervolemia.
      Anesthetized rats were pretreated with the dopamine receptor blockers haloperidol
      (1 mg.kg-1 body weight, i.p.), SCH 23390 (30 micrograms.hr-1.kg-1 i.v.) or
      vehicle and then subjected to VE at 2, 5 or 10% of body weight per hour. VE at 2,
      5 and 10% increased sodium excretion in vehicle-pretreated animals 6-, 29- and
      130-fold, respectively. In the haloperidol-pretreated animals the natriuretic
      response (accumulated sodium excretion) to VE was attenuated by 67% (P less than
      0.05), 46% (P less than 0.05) and 22% (NS) at the three degrees of expansion,
      respectively. The corresponding attenuation in SCH 23390-treated animals were 60%
      (P less than 0.05), 56% (P less than 0.05) and 19% (NS), respectively. The
      gradual decrease in attenuation indicates that at varying degrees of
      hypervolemia, different physiological systems contribute differently to the renal
      natriuretic response. The dopamine system seems to be relatively more important
      in promoting natriuresis at the lower (physiological) range of hypervolemia
      whereas in the high range other factors have a greater impact.

PMID- 2002640
TI  - Direct vasopressor effect of recombinant human erythropoietin on renal resistance
      vessels.
AB  - The contractile properties of recombinant human erythropoietin (rHuEPO) on
      isolated resistance vessels of renal and mesenteric vascular beds were studied in
      an in vitro model using a small vessel myograph. Under isometric conditions,
      rHuEPO caused a contraction of this vasculature in a concentration range between
      10 U/ml and 200 U/ml. A maximal active wall tension of 1.52 +/- 0.19 mN/mm was
      obtained under a rHuEPO dose of 200 U/ml. In Ca2+ free solution, the pressor
      response to high rHuEPO-concentrations was attenuated, and the response to low
      rHuEPO concentrations was abolished. In the presence of verapamil, phentolamine
      and saralasin, rHuEPO-induced contractions were not affected significantly. A
      dose-dependent vasodilatation of mounted vasculature to acetylcholine (ACh)
      indicated that endothelium remained intact in our preparations. rHuEPO-induced
      vessel contraction was not abrogated after an enzymatical removal of endothelium
      by collagenase, confirming that the described contractile responses are
      endothelial independent. These findings suggest that a direct vasopressor effect
      of rHuEPO on proximal resistance vessels may contribute to development of
      hypertension seen in rHuEPO-treated hemodialysis patients.

PMID- 2002641
TI  - Intracellular H+ buffering power and its dependency on intracellular pH.
AB  - Intracellular hydrogen ion (H+) buffering power, conventionally defined as the
      amount of acid or base that would have to be introduced into the cell cytosol to
      decrease or increase ipH by one pH unit, is generally said to increase as
      intracellular pH (ipH) decreases. This implies that the cell has a lesser
      capability to resist acute acid or base perturbations at its steady state ipH
      than at any lower ipH. We re-examined this notion, reasoning that the logarithmic
      nature of the pH unit could limit the validity of the conventional expression of
      buffering power in imparting physiologic insight into the mechanisms of cellular
      H+ homeostasis. The mathematical derivation of the formula, delta i[NH4+]/delta
      ipH, conventionally used to estimate buffering power using the NH4Cl technique,
      revealed that this parameter is, by design, inversely proportional to the
      exponential of ipH. This a priori dependence on pH dictates an increase in
      buffering power with decreasing ipH, and thereby interferes with the assessment
      of the physiologic capability of the intracellular milieu to buffer protons at
      different ipH levels. To circumvent this problem, buffering power was defined as
      the amount of hydrogen ions that would have to be added to or removed from the
      cell to effect a change in the concentration of H+ in the cell cytosol of 1 mM (a
      term heretofore referred to as the cell H+ buffering coefficient). The
      mathematical derivation of the formula used to calculate the cell H+ buffering
      coefficient, delta i[NH4+]/delta[H+]i, does not suffer from an a priori
      dependence on ipH.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2002642
TI  - Osmoregulation of thirst and vasopressin release in severe chronic renal failure.
AB  - Subjects with severe chronic renal failure (CRF) have higher plasma
      concentrations of arginine vasopressin (AVP) than normal subjects, and some
      develop severe thirst. Eight patients with CRF and seven matched controls
      underwent hypertonic saline infusion to explore the relationship of thirst and
      plasma AVP with plasma osmolality. Differences in urea concentration between the
      two groups were controlled for by correcting measured osmolality to a urea of
      zero. Linear regression analysis of the relationships between plasma AVP and
      thirst with plasma osmolality (corrected for urea) was performed. Mean results
      were: control, pAVP = 0.26 (pOsmc - 283.7) versus CRF, pAVP = 0.72 (pOsmc -
      282.0); and control, thirst = 4.0 (pOsmc - 279.4) versus CRF, thirst = 3.5 (pOsmc
      - 281.8). The apparent sensitivity (slope) of AVP release was greater in severe
      CRF than in normal controls (P = 0.04). There was no significant difference
      between the groups in thirst sensitivity, threshold for thirst onset and
      threshold for AVP release. Osmoregulated thirst was normal in severe CRF, but
      increasing osmolality leads to higher concentrations of AVP than would be
      expected.

PMID- 2002643
TI  - Treatment of hepatitis B virus-associated membranous nephropathy with adenine
      arabinoside and thymic extract.
AB  - Previously we found that corticosteroid treatment in the hepatitis B virus (HBV)
      associated membranous nephropathy (HBVMN) was not associated with a favorable
      outcome. To distinguish the differences of the HBV DNA in macrophage, T and B
      cells among HBVMN patients with or without corticosteroid treatment, serial
      studies at different time points were investigated. HBV DNA appeared as an
      "episomal" molecule as with 3.2 kb in macrophage, T and B cells. This molecule
      disappeared after 12 months among HBVMN patients without corticosteroid
      treatment. HBV DNA, by contrast, appeared as episomal form even three years later
      in T cells, with frequent proteinuria among HBVMN patients with corticosteroid
      treatment. This finding indicates that the use of corticosteroids leads to a
      potential risk of enhancing HBV viral replication in T cells. We studied 24 HBVMN
      patients who had previously received corticosteroid treatment and had persistent
      proteinuria, who were administered combination therapy with adenine arabinoside
      for two weeks and thymic extract (Thymostimulin) for six months to decrease urine
      protein loss and obtain seroconversion. These 24 patients had heavy (22 of 24,
      91.6%) or mild (2 of 24, 8.4%) proteinuria prior to adenine arabinoside and
      thymostimulin treatment. All 24 patients demonstrated HBV DNA in mononuclear
      cells and simultaneously exhibited sera positive with HBsAg and HBeAg. In
      contrast, after treatment only one case (4.2%) had heavy and two cases (8.4%)
      mild proteinuria; HBV DNA was demonstrated in macrophage (4 of 24, 16.7%), T
      cells (9 of 24, 37.5%), and B cells (6 of 24, 25%) as well as serum (24 of 24,
      100%) prior to treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2002644
TI  - Urinary excretion of endothelin-1 in normal subjects and patients with renal
      disease.
AB  - To elucidate the pathophysiological significance of urinary endothelin-1 (ET-1),
      we measured urinary excretion of ET-1-like immunoreactivity (L1) in 17 patients
      with renal disease and 9 normal subjects. Twenty-four hour urinary ET-1-L1
      excretion in patients with renal disease (358 +/- 68 ng, mean +/- SE) was
      significantly (P less than 0.005) greater than that of normal subjects (77 +/- 5
      ng). In patients with renal disease. ET-1-L1 clearance (CET) exceeded creatinine
      clearance (CCR); CET/CCR (305 +/- 81%) was significantly (P less than 0.005)
      greater than that of normal subjects (43 +/- 13%). The 24-hour urinary excretion
      of ET-1-L1 in patients with renal disease showed significant correlation with
      that of N-acetyl-beta-D-glucosaminidase (r = 0.587, P less than 0.05), beta 2
      microglobulin (r = 0.614, P less than 0.01) and albumin (r = 0.484, P less than
      0.05). Intravenous infusion of saline (500 ml) in seven normal subjects did not
      affect urinary ET-1 excretion rate. These data suggest that urinary excretion of
      ET-1 derives mainly from renal tubular secretion at least in patients with renal
      disease, and that degradation and/or reabsorption of ET-1 at the tubular site may
      also contribute to the renal handling of ET-1. Therefore, urinary excretion of ET
      1 should serve as a potential marker for renal injury.

PMID- 2002645
TI  - Phagocytosis in uremic and hemodialysis patients: a prospective and cross
      sectional study.
AB  - Leukocyte response to phagocytic challenge was assessed in uremic and
      hemodialysis patients in a prospective and cross sectional study. Using latex,
      zymosan and staphylococcus as phagocytic challenge, the utilization of glucose-I
      C14 and the generation of reactive oxygen species was measured in these patients.
      In uremic, non-dialysis dependent patients, the response to phagocytosis was
      significantly reduced when creatinine exceeded 6 mg/dl and prior to initiation of
      dialysis (mean serum creatinine 9.3 +/- 0.3 mg/dl) was less than half that of
      patients with normal renal function (P less than 0.01). In a prospective study of
      15 patients initiated on dialysis, the metabolic response of their leukocytes was
      assessed sequentially. In eight patients, initiation of dialysis with cuprophane
      (Cu) membrane lead to a further decline (60%) in their metabolic response to
      phagocytosis at the end of four weeks of dialysis compared to pre-initiation of
      dialysis (P less than 0.01), whereas in seven other patients, dialysis with non
      complement activating membranes did not result in a significant decline.
      Prospective cross-over studies of chronic hemodialysis patients corroborated
      these findings; eight patients dialyzed with new CU membranes had a significant
      decline of their metabolic response to phagocytic challenge acutely at the end of
      each dialysis and in pre-dialysis samples after two weeks of Cu dialysis, whereas
      their response returned back to baseline after two weeks of dialysis with non
      complement activating membrane. In prospective and cross sectional studies, a
      decreased response to phagocytic stimulus was a predictor of hospitalization,
      primarily for infectious reasons.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2002646
TI  - Effect of cyclosporin A on immunoglobulin class in patients receiving blood
      transfusions.
AB  - IgG antibodies detected by flow cytometry in sera from potential renal transplant
      recipients are associated with an increased number of rejection episodes and
      impaired graft function. Furthermore, cytotoxic antibodies may develop if pre
      transplant blood transfusions are given to such patients. We have investigated
      the effect of cyclosporin A on the development of IgM and IgG antibodies detected
      by flow cytometry after blood transfusions in 16 previously untransfused dialysis
      patients. Eight (group 1) received three to five third-party blood transfusions
      at two weekly intervals and the remaining eight (group 2) received transfusions
      with concomitant cyclosporin A therapy (10 mg/kg/day). Sera obtained after each
      transfusion were tested using flow cytometry against lymphocytes from six normal
      donors. In all 462 serum/cell combinations were tested. Sera from six out of
      eight patients in group 1 showed IgG antibody activity following blood
      transfusions and none developed IgM antibodies alone. In contrast IgG antibody
      activity was detected in one serum sample from only one of the eight patients in
      group 2 (P less than 0.02); a further three patients developed IgM but not IgG
      antibody activity during the transfusion protocol. IgG antibodies were found in
      25/228 serum/cell combinations in group 1 but in 1/234 in group 2 (P less than
      0.001). The patient in group 2 who developed IgG antibodies in one serum/cell
      combination was known to have red cell autoantibodies. This IgG activity was
      removed by red cell absorption, suggesting that the autoreactive red cell
      antibody cross-reacted with lymphocytes. Cytotoxic antibodies were detected in
      two serum/cell combinations in group 1 alone.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2002647
TI  - Nitric oxide synthesis inhibitor prevents vasodilation by insulin-like growth
      factor I.
AB  - The effect of insulin-like growth factor I (IGF-I) on renal blood flow was
      measured in the anaesthetized rat using an electromagnetic flow probe. Renal
      vasodilation induced by IGF-I (50 micrograms/kg) was completely inhibited by NG
      nitro-l-arginine methyl ester (50 mg/kg), an inhibitor of nitric oxide
      biosynthesis, but only partially reduced by indomethacin (10 mg/kg). The
      involvement of nitric oxide synthesis in the renal actions of IGF-I is proposed.

PMID- 2002648
TI  - Diuretics.

PMID- 2002649
TI  - Abstracts of the XVIII biannual meeting of the South African Renal Society.
      Johannesburg, South Africa, August 5-9, 1990.

PMID- 2002650
TI  - What can be learned from the expression of endothelial adhesion molecules in
      tissues?

PMID- 2002651
TI  - Expression of human major histocompatibility antigens on germ cells and early
      preimplantation embryos.

PMID- 2002652
TI  - Leukocyte involvement in the pathogenesis of pulmonary injury in experimental
      Goodpasture's syndrome.
AB  - To investigate the role of leukocytes in the pathogenesis of pulmonary injury
      after antibody deposition on the alveolar basement membrane, we have induced
      experimental Goodpasture's syndrome in the rat using passive accelerated anti
      glomerular basement membrane (GBM) disease. Animals were immunized with normal
      rabbit IgG and given either rabbit anti-rat GBM serum or normal rabbit serum
      (control) 5 days later. In this model, leukocytic infiltration, severe
      hemorrhage, and granulomatous-like lesions developed in the lung, while a rapidly
      progressive glomerulonephritis was evident in the kidney. Within 30 minutes of
      injection of anti-GBM serum, strong linear deposition of antibody on both
      glomerular and alveolar basement membranes was evident. In the lung, a transient
      influx of polymorphonuclear cells during the first 12 hours was closely followed
      by macrophage infiltration, with T cell infiltration not evident until day 3.
      Pulmonary hemorrhage correlated with ED1+ macrophage infiltration (p less than
      0.001), but not with OX-19+ T cell accumulation. Many activated mononuclear cells
      were found in the lung infiltrate from day 14 onward and were associated with
      areas of tissue damage. This study demonstrates the feasibility of using passive
      accelerated anti-GBM disease as a model of Goodpasture's syndrome, and suggests
      that inflammatory macrophages are the major cellular participants in progressive
      pulmonary injury after antibody deposition.

PMID- 2002653
TI  - Leakage and neuronal uptake of serum protein in aged and Alzheimer brains. A
      postmortem phenomenon with antemortem etiology.
AB  - Abnormal extravasation of serum proteins has frequently been reported in
      Alzheimer's disease (AD) and less often in nondemented, aged individuals. In
      order to establish whether these are ante or postmortem phenomena, we have now
      compared the immunocytochemical localization of immunoglobulin in young, aged,
      and AD brains. In all the young brains, but only in some of the aged and AD
      brains, immunoglobulin was confined to a fine network of microvessels. In
      contrast, the majority of AD, as well as apparently normal, aged brains revealed
      both focal and diffuse extravascular localization in the form of neuronal
      labeling as well as a general, diffuse background. Since microvessels in these
      areas were no longer revealed, it was felt that the extravascular leakage
      occurred postmortem at a time when replacement of intravascular immunoglobulin
      had ceased. Furthermore, there was a correlation between the extent of leakage
      and time interval between death and autopsy. Postmortem leakage of serum protein
      was reproduced in a more controlled system using young and aged rats; serum
      protein leakage evolved from focal to diffuse patterns in aged brains as the
      postmortem period increased, whereas the leakage was restricted to the outer half
      of the cortices in young brains even after a prolonged postmortem period.
      Postmortem trauma to the rat brain also caused lesion-related leakage as well as
      neuronal labeling. It was concluded that extravascular leakage and neuronal
      uptake in aged and AD brains is a postmortem phenomenon, due to delay in autopsy
      or mishandling of brains, but dependent in severity upon antemortem
      circumstances.

PMID- 2002654
TI  - Immunoglobulins stimulate central nervous system remyelination: electron
      microscopic and morphometric analysis of proliferating cells.
AB  - Infection with the Daniel strain of Theiler's murine encephalomyelitis virus
      results in immunemediated primary demyelination in the spinal cords of
      susceptible SJL/J mice. Treatment of chronically infected mice (3 to 7 months)
      with purified immunoglobulins directed against spinal cord homogenate resulted in
      an increase in the number and average size of lesions that were undergoing
      remyelination by oligodendrocytes. In vivo autoradiography with [3H]thymidine
      demonstrated labeling of many lymphocytes in areas of demyelination and
      remyelination. A direct correlation was found between number of labeled
      lymphocytes infiltrating the lesion and size of demyelinating lesions.
      Remyelinated areas contained proliferating cells that resembled immature
      oligodendrocytes or progenitor glial cells morphologically. The number of labeled
      presumptive glial cells correlated with the area of remyelination. However,
      central nervous system remyelination occurred even in the presence of
      proliferating lymphocytes and astrocytic hypertrophy. In addition, treatment of
      normal uninfected SJL/J mice with antiserum to spinal cord homogenate resulted in
      increased numbers of proliferating cells in the spinal cord. These experiments
      suggest that immunoglobulins to a spinal cord antigen may induce proliferation of
      cells in the central nervous system to promote remyelination.

PMID- 2002655
TI  - Longitudinal study of solute excretion and glomerular ultrastructure in an
      experimental model of aging rats free of kidney disease.
AB  - Because experimental studies of kidney aging are frequently complicated by the
      presence of renal disease, we set out to define a model minimizing renal
      pathology and thus revealing basic aging phenomena. Male and female Wistar/Lou
      rats were conceived, born, and bred to 42 months in a specific pathogen-free
      husbandry. They had free access to water and to a protein diet containing 2% fish
      and 15% vegetable proteins. The mean survival ages of this colony were 39 months
      for females and 35 months for males. Body weight, 24-hour food and water intake,
      urinary volume, and solute excretion were measured every 6 months in a group of
      12 males and 12 females. Throughout the study, the mean body weight remained
      close to 180 gm in females and 320 gm in males. Despite this size difference,
      absolute daily food intake was similar in the two sexes and almost constant over
      the studied period. Age-related changes in proteinuria and phosphate excretion
      were greater in males than in females. Decreased urine osmolality and increased
      urinary volume, on the other hand, were more pronounced in old females than in
      males. Renal loss of calcium was noticed in both sexes and glucosuria remained
      discrete. Kidneys examined at 12, 24, and 36 months in both sexes and also at 42
      months in females were free of major pathology such as pronounced
      glomerulosclerosis, tubular nephrosis, tubular cast, or hydronephrosis. In the
      oldest animals a few foci of interstitial inflammation occasionally were seen.
      The sole significant morphologic change was a regular but moderate thickening of
      the glomerular basement membrane, which roughly doubled its size from 12 to 36
      months. Morphometric studies failed to demonstrate an increase in mesangial
      matrix or mesangial cellularity. No changes in foot processes, slit diaphragms,
      or endothelial fenestrae were seen with increasing age. These observations
      indicate that basic age-related changes in kidney structure and function of rats
      fed ad libitum can be reduced to a few parameters provided that adequate strains,
      diet, and husbandry conditions are selected for experimentation.

PMID- 2002656
TI  - Macula densa morphology in diabetic rats with and without hyperglycemia and in
      nondiabetic hyperglycemic rats.
AB  - The morphology of the macula densa was studied in streptozotocin diabetic insulin
      treated rats with hyperglycemia for 50 days, and in three groups of diabetic rats
      that were first hyperglycemic for 50 days and then put onto different insulin
      regimes to achieve normoglycemia. One of the latter groups of rats was given a
      single dose of insulin and was studied 4 hours later when the animals were
      normoglycemic. The other two groups were treated with insulin for 5 and 15 days
      in such a way that the animals were nearly normoglycemic throughout the treatment
      period. In a further set of experiments two groups of nondiabetic rats were made
      hyperglycemic by intravenous injection of glucose and studied after 1 and 10
      minutes of hyperglycemia. A perfusion fixation of the kidneys was performed in
      all animals with a 1% glutaraldehyde solution retrograde through the aorta, and
      the tissue was embedded in Epon for light and electron microscopy.
      Juxtaglomerular apparatuses were randomly selected from thick sections and
      reembedded for electron microscopy. The volume density of the lateral
      intercellular spaces (LIS) between the macula densa cells was determined on
      electron micrographs, by use of a morphometric technique. The study showed that
      the volume density of the LIS comprised about 10% in the nondiabetic
      normoglycemic animals and about 1.5% in the diabetic hyperglycemic animals. In
      all the insulin-treated normoglycemic diabetic animals, the volume density of the
      LIS was the same as in the nondiabetic normoglycemic animals (about 10%),
      independent of the duration of the insulin treatment. In the nondiabetic
      hyperglycemic animals the volume density of the LIS comprised about 1.5%, as in
      the diabetic hyperglycemic animals. In conclusion, the volume density of the LIS
      between the macula densa cells is reduced in a hyperglycemic state, irrespective
      of how the hyperglycemia was achieved, and they are normalized (i.e., enlarged)
      in insulin-treated diabetic normoglycemic animals irrespective of the duration of
      the treatment. The results indicate that changes in the blood glucose
      concentration have a major impact on the size of the macula densa LIS.

PMID- 2002657
TI  - Studies on the thymus in nonobese diabetic mouse. I. Changes in the
      microenvironmental compartments.
AB  - The nonobese diabetic (NOD) mouse develops an autoimmune type I diabetes, which
      is predominantly seen in females, is triggered by T cells, and whose frequency is
      enhanced following thymectomy at weaning. Attempting to characterize a thymic
      pathology in these animals, we analyzed the microenvironmental compartment of the
      organ with respect to structural and functional molecules expressed by thymic
      epithelial cells (TEC), as well as extracellular matrix components. We observed,
      in both males and females, a precocious decrease in the cell numbers of discrete
      medullary TEC subsets, namely, those respectively defined by the expression of
      cytokeratins 3/10 and cytokeratin 19. In addition, some cells bearing the TR.5
      phenotype (normally restricted to the medulla) could be detected in the NOD mouse
      thymic cortex. There was also a significant early decrease in thymulin production
      in females, as compared to males. As regards the extracellular matrix
      compartment, the most striking alteration was the presence of abnormally enlarged
      perivascular spaces, increasing in size with age. In these structures large
      amounts of T cells and, to a lesser extent, B cells were consistently
      encountered. In addition to B cells, the NOD mouse thymus showed on both TEC and
      extracellular matrix the presence of deposits of immunoglobulins, revealed with
      fluorescence-labeled goat anti-mouse Ig sera. Finally, the NOD mouse sera labeled
      both TEC and extracellular matrix proteins on normal mouse thymus frozen
      sections. Together, these data clearly demonstrate that the NOD mouse thymus
      undergoes a variety of microenvironmental changes, whose particular role in the
      pathophysiology of the disease is yet to be demonstrated.

PMID- 2002658
TI  - Distribution and pattern of expression of villin, a gastrointestinal-associated
      cytoskeletal protein, in human carcinomas: a study employing paraffin-embedded
      tissue.
AB  - Villin is a 95-kilodalton gastrointestinal-related cytoskeletal protein
      associated with axial microfilament bundles of brush border microvilli. We tested
      the hypothesis that expression of this protein was restricted to adenocarcinomas
      of gastrointestinal origin in a retrospective study of 203 human neoplasm that
      had been fixed in Carnoy's or methacarn fixative and embedded in paraffin. Villin
      expression was restricted to a subset of epithelial tumors, with no expression
      noted in any cases of sarcoma, melanoma, or lymphoma. Villin proved to be a very
      sensitive and relatively specific marker of gastrointestinal adenocarcinomas: all
      colonic, gastric, and pancreatic carcinomas were positive, and none of the breast
      or lung carcinomas were positive, with the single exception of a bronchioalveolar
      adenocarcinoma. However, a subset of nongastrointestinal adenocarcinomas,
      including some adenocarcinomas of ovary, endometrium, and kidney, were also
      positive. Nonetheless, at least three distinct patterns of villin expression were
      discerned, some of which were quite specific for individual tumor types. Thus, an
      apical or brush border pattern of villin expression was seen in virtually all
      gastrointestinal adenocarcinomas, as well as in the occasional villin-positive
      endometrial or ovarian adenocarcinomas. A membranous distribution of carcinomas,
      mimicked the patterns of the normal counterpart tissue, e.g., delineation of bile
      canalicular structures. Finally, no relationship was found between the presence,
      or pattern of expression, of villin and the state of tumor differentiation. It is
      concluded that antibodies to villin may play an important role in
      immunocytochemical analyses of poorly differentiated malignant tumors in
      appropriately fixed, paraffin-embedded tissue and in cases where the primary site
      is indeterminant from clinical history and histology.

PMID- 2002659
TI  - Culture and characterization of microvascular endothelial cells derived from
      human brain.
AB  - Primary cultures of human cerebral endothelial cells were established from
      microvessels isolated from cortical fragments removed at surgery for seizure
      disorder and from brains at autopsy. A uniform population of cells growing in
      close association to each other formed confluent monolayers by 7 to 10 days in
      culture. They contained factor VIII/Von Willebrand antigen, the most specific
      marker for cells of endothelial origin, and showed lectin-binding sites for Ulex
      europaeus agglutinin characteristic of human endothelium. Cultured cells formed
      thin, continuous monolayers, contained few pinocytotic vesicles, and were joined
      together by tight junctional complexes. More than 99% of the intercellular
      junctions restricted the transendothelial passage of horseradish peroxidase.
      Monolayers of human brain microvessel endothelial cells thus resemble cerebral
      endothelium in vivo and should provide a useful in vitro model for studies of the
      biology of these cells and their role in the pathogenesis of certain human
      central nervous system diseases associated with abnormal blood-brain barrier
      function.

PMID- 2002660
TI  - An animal model for the study of azidothymidine-induced hyperpigmentation.
AB  - Mice fed azidothymidine demonstrated dramatic hyperpigmentation of their tails.
      Histologic examination demonstrated large quantities of melanin pigment
      throughout the entire epidermal layer. Control mice had scant melanin pigment
      localized to the basal layer. Our findings demonstrate that the mouse is a useful
      model for the investigation of drug-induced hyperpigmentation.

PMID- 2002661
TI  - The Adult Health Care Consent Act: new legislation governing treatment of
      incompetent patients in South Carolina.

PMID- 2002662
TI  - Breast cancer: highlights for the nineties.

PMID- 2002663
TI  - Coronary bypass surgery for the elderly.

PMID- 2002664
TI  - Stereotactic neurosurgery in the management of deep lesions in the brain.

PMID- 2002665
TI  - Adolescent pregnancy: effects of nutrients on hematocrit and birth weight in
      Orangeburg County.
AB  - Effect of nutrients on hematocrit and birth weight during teenage pregnancy was
      studied for both Blacks and non-Blacks in Orangeburg County. The results of this
      study indicated that both Blacks and non-Blacks were considered to be at risk for
      nutritional anemia, based on hematocrit values. It further showed that Blacks and
      non-Blacks consumed an inadequate diet, particularly in iron and folic acid.

PMID- 2002666
TI  - Numerical schemes for unsteady fluid flow through collapsible tubes.
AB  - The study of fluid flow through compliant tubes is a fluid-structure type
      problem, in which a dynamic equilibrium is maintained between the fluid and the
      tube wall. The analogy between this flow and gas dynamics initiated the use of a
      number of numerical methods which were originally developed to solve compressible
      flow in rigid ducts. In this study we investigate the solutions obtained by
      applying the Lax-Wendroff and MacCormack schemes to one-dimensional
      incompressible flow through a straight collapsible tube. The time-evolving
      numerical results were compared with exact steady-state solutions. For boundary
      conditions which were held fixed after a prescribed rise time, the unsteady
      numerical solution converges to the exact steady-state solution with very good
      accuracy. The stability and accuracy of all the methods depend on the amount of
      viscous pressure loss dictated by wall friction. Flows with undamped oscillations
      cannot, however, be solved with these techniques.

PMID- 2002667
TI  - Clinical trials of a dual-sensor diagnostic pacemaker.
AB  - The results of clinical trials of a dual-sensor diagnostic pacemaker are
      described. The system monitors and records intraventricular electrical and
      pressure waveforms using a special lead incorporating bipolar electrodes together
      with a piezoelectric pressure transducer. The recorded waveforms, which are shown
      in conjunction with Holter recordings made simultaneously, demonstrate the value
      of pressure measurements and illustrate several cardiac events, including an ECG
      pause, bradycardia, a pressure pause, ectopic beats and tachycardia. The pacing
      function of the device is shown and capture is demonstrated.

PMID- 2002668
TI  - A lung function information system.
AB  - A lung function information system (LFIS) was developed for the data analysis of
      pulmonary function tests at different locations. This system was connected to the
      hospital information system (HIS) for the retrieval of patient data and the
      storage of the lung function variables of patients to generate follow-up reports
      and to support financial and administrative management. The application programs
      were developed in such a way that high flexibility was obtained with respect to
      the patient-computer-technician interaction. The sampled data are stored on a
      disc to correct earlier decisions, perform recalculations and reanalyse the data
      for research purposes. When the measurements performed on a patient are
      authorized, the sampled data are deleted, except for when they are needed for
      future research. A distributed computer system was chosen to combine the benefits
      of a centralized system with those of several stand-alone systems. The main tasks
      of the central unit are to store collected data and computer programs, generate a
      final lung function report on laser printer and provide a connection to the HIS.
      In the satellite computers, which are located close to the lung function
      equipment, the signals and raw data are processed. Furthermore, the satellite
      computers were in use for program development and several research projects, and
      for the offline data processing of the lung function measurements from two other
      hospitals by means of a modem connection. The LFIS improved the quantity and
      quality of data acquisition. It resulted in an increased capacity of about 50%
      concerning spirometry, and facilitated time-consuming complex analyses. It also
      avoided miscalculations and mistakes in reports previously experienced with hand
      calculations.

PMID- 2002669
TI  - Computer-aided design and manufacture of an above-knee amputee socket.
AB  - This paper describes the initial test results obtained from a newly developed
      computer-aided socket design (CASD) and manufacturing (CASM) process for above
      knee amputees. Anthropometric measures taken from an amputee provided input
      information to a CASD system. Using these measurements, data from a reference
      shape library stored in the computer were selected and modified to create a
      unique socket shape reflecting the particular characteristics of the amputation
      stump. The resultant shape was produced as a 'primitive' test socket by a CASM
      process. Numerical shape data were then transferred to a CNC milling machine to
      construct a negative cast, from which the primitive socket was produced by a
      vacuum-forming procedure. The resultant primitive socket shape was fitted and the
      amputee was able to load the socket without discomfort. Some shape discrepancies
      were identified and the shape data were modified interactively by the CASD system
      to create a final socket shape. The final socket shape was manufactured and worn
      by the amputee during a 35 min walking trial. Subjective evaluation was that the
      socket provided comfort and control comparable with that of the conventional
      socket, and proved to be acceptable to the amputee. This was followed by a 2
      month home trial which was also successful. The CASD socket shapes were compared
      numerically in area, shape and volume with data taken from the original socket
      worn by the amputee, a new socket made by conventional methods and a topographic
      model of the amputation stump. The final CASD socket shape compared favourably
      with that of a socket manufactured by conventional methods.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 2002670
TI  - Vibration arthrometry in assessment of knee disorders: the problem of angular
      velocity.
AB  - A knee joint that has sustained a painful injury will typically require skillful
      examination, by an orthopaedic surgeon, for signs of internal damage. These signs
      include characteristic sounds and vibrations, which are produced by the knee when
      it is stressed. The technique of vibration arthrometry is being developed to
      assist the clinical examiner in identifying these vibrations and to improve
      diagnostic accuracy. To detect and record the knee vibrations, small lightweight
      accelerometers are positioned on various bony prominences around the knee. These
      produce electronic signals which permit objective analysis of the vibration
      characteristics. It has been found that varying the investigative procedure can
      affect the magnitude of some parameters of the vibration signal. If these
      parameters are to be used in evidence of knee pathology, the effect of the
      investigative procedure must be normalized. The effect of speed of joint movement
      has been quantified in a pilot study involving 24 patients with internal knee
      damage. Custom-designed hardware was used to measure joint speed as the rate of
      change of joint angle, which was measured by an electrogoniometer. It was found
      that the energy content of the vibration, reflected by the peak amplitude and
      root mean square value was strongly affected by joint speed. However, the
      characteristic shape of the vibration, reflected by the peak frequency in the
      harmonic spectrum of the signal, remained similar for the range of joint speed in
      the investigation.

PMID- 2002671
TI  - Study of the relative timing of shear forces on the sole of the forefoot during
      walking.
AB  - A portable recording device for the measurement of ambulatory longitudinal shear
      forces in a horizontal plane under the forefoot is described. The timing of the
      shear forces under 40 feet has been investigated, together with the relationships
      to each other and to body weight, leg length, cadence, velocity and stride
      length: they are compared by regression analysis. Shear forces under the forefoot
      are shown to occur for approximately 73-80% of the stance time. The maximum
      longitudinal shear forces and the maximum vertical forces are shown to occur at
      the same time under the first, fourth and fifth metatarsal heads.

PMID- 2002672
TI  - Arteriovenous ratios of angiotensin II during acute infusion experiments: a model
      based analysis.
AB  - The hormone angiotensin II (AII) is a vasoconstrictor known to participate in the
      natural regulation of blood pressure via the renin-angiotensin system. A third
      order model was developed which describes the dynamics of venous and arterial
      plasma AII concentrations (PAC) and mean arterial blood pressure (BP) during
      acute constant rate AII infusion experiments. The model is calibrated using
      approximate blood circulation rates and steady-state PAC and BP data for
      published experiments in sheep. Analysis of the dynamic model demonstrates that
      local changes in PAC during the first several minutes of acute infusion are
      characterized by the comparatively rapid distribution of exogenous AII making its
      forward passage across the blood circulation, combined with the more gradual
      elevation of exogenous AII recycled through the circulation. This analysis
      explains the observed divergence in physiological levels of venous and arterial
      PAC at steady state in terms of the monotonic net clearance of elevated levels of
      circulating AII along the circulatory path between the point of infusion and the
      two sites at which the PAC measurements are taken. The model suggests that the
      differing arteriovenous AII concentration ratios and differing PAC and BP
      relationships reported for different dose-response experiments may be explained
      in part by differences in the specific infusion and measurement sites employed in
      those experiments.

PMID- 2002673
TI  - Decision support system for the differential diagnosis of breast disease.
AB  - The histopathological diagnosis of breast disease is representative of many
      problems of differential diagnosis encountered in the medical domain. It requires
      highly trained and experienced experts and is characterized by a large number of
      features whose presence or absence involves much uncertainty. Computer-based
      decision support systems intended to function in a consultative capacity during
      differential diagnosis have had limited success for two fundamental reasons.
      Firstly, they take an autonomous role and assume that the user has no
      contribution to make to the problem-solving process. Secondly, the established
      techniques for representing and reasoning with medical knowledge are of limited
      suitability in this domain. Such systems are unable to reach a correct diagnosis
      quickly and often subject the user to a cumbersome dialogue. These are not
      tolerated by pathologists working under severe time constraints. We first look at
      the problem-solving methods employed by pathologists in this domain and examine
      the functionality of traditional expert system methodologies. We then present a
      cooperative design which allows the pathologists to express his or her ideas
      within a decision support system whilst gaining assistance in required areas. A
      novel inference technique based upon the set partitioning technique in
      hypergraphs is also described. This mathematical method has the ability to cope
      with the incomplete or inadequate knowledge which is a characteristic of breast
      disease, whilst directing data gathering in a meaningful manner. In particular
      this approach can significantly reduce the amount of irrelevant data which the
      pathologist must enter before a conclusion is reached. Thus it can potentially
      improve the efficiency and user acceptability of medical expert systems.

PMID- 2002674
TI  - Response of human femur to mechanical vibration.
AB  - The effect of mechanical vibration in the frequency range 0-500 Hz on the
      cadaveric human femur was assessed. It was found that when the bone was fixed at
      both ends, its resonant frequency was markedly affected by end loading and
      damping. If the conditions of the experiment were designed to simulate the
      condition of the femur when prepared for a total hip replacement, it was found
      that the bone did not resonate but behaved in a mass-like mode. The significance
      of this observation is that in the event of vibration being applied to enhance
      the penetration of bone cement, the movement induced in the bone will be
      proportional to the force applied regardless of frequency. This also demonstrates
      that the concept of designing a prosthesis so that it is isoelastic with the
      femur is complex and potentially flawed, since the stiffness of the femur will
      vary during the walking cycle.

PMID- 2002675
TI  - In vitro investigation of the factors affecting pulse oximetry.
AB  - The effect of a number of physiological parameters on pulse oximetry accuracy has
      been investigated in an in vitro model. We have found that above 50% saturation,
      pulse oximeters will not be affected by variations in haematocrit, blood flow
      rate, tissue blood content and pulse amplitude. At low saturations, however, it
      is known that the accuracy of pulse oximeters decreases and our in vitro results
      suggest how this may be corrected.

PMID- 2002676
TI  - Stretch reflex inhibition using electrical stimulation in normal subjects and
      subjects with spasticity.
AB  - The effect of electrically stimulating the tibialis anterior muscle on the
      stretch reflex of the soleus muscle in normal subjects and subjects with
      spasticity is investigated. Stimulation of the tibialis anterior just prior to
      the onset of a mechanical disturbance, which causes a stretch in the soleus,
      inhibits the stretch reflex of the soleus in normal subjects and may inhibit
      clonus in subjects with spasticity.

PMID- 2002677
TI  - Parameters of the ulnar medullary canal for locked intramedullary nailing.
AB  - The development of a 'one shot' locked intramedullary device for rapid
      stabilization of adult ulnar fractures would benefit surgeon and patient alike,
      but before a prototype device can be manufactured, basic internal measurements of
      the ulnar medullary canal are needed. Various sections and measurements of 142
      adult human cadaver ulnas were performed to determine the calibre, length and
      curvature of the medullary canal. These measurements revealed that the device can
      be of one calibre but will need manufactured in three different lengths. Because
      of the minimal curvature of the ulnar medullary canal and the ability to lock the
      nail both proximally and distally, the nail can be straight and inserted loosely.
      A prototype design is described.

PMID- 2002678
TI  - Simulating gas flow through the exhalation leg of a respirator's patient circuit.
AB  - The effectiveness of prescribed respiratory therapy is often dependent upon the
      choice of a respirator (ventilator) that excels for a particular mode of
      ventilation. The exhalation value of a ventilator is most often the key to a
      strong or weak performance. A computer model of the patient's gas flow through
      the expiratory circuit and exhalation valve is not only beneficial for design,
      but can also be used to study the optimum performance for a particular mechanical
      system. For this paper, the system that was used incorporated a linear voice coil
      actuator suspended by flat spider springs. The details of the modelling are given
      on a theoretical basis (with the appropriate equations), and the packaged
      simulation is described. Results are presented for simple computer algorithms
      with the intention of demonstrating the proper behaviour of the system. There are
      suggestions for further detailed studies to compare the linear voice coil model
      with other common exhalation valve mechanical designs, under various modes of
      ventilation.

PMID- 2002680
TI  - A simple low cost footswitch.

PMID- 2002679
TI  - Clinical temperature acquisition using proximity telemetry.
AB  - This paper describes an electronic clinical thermometer which does not require a
      cable connection between the sensor and the temperature indicator. Several
      patients using individual battery-powered sensors can have their temperatures
      logged by a hand-held interrogating device held in close proximity. Temperature
      readout is virtually instantaneous and there is no interference between adjacent
      users. The device relies on radiofrequency-tuned circuit coupling for its
      operation.

PMID- 2002681
TI  - Dr. Carl Beck and the Mayos.

PMID- 2002682
TI  - Microvascular pedal bypass for salvage of the severely ischemic limb.
AB  - Bypass to the pedal arteries was performed with use of the operating microscope
      and standard microsurgical technique in 37 patients with severe, chronic ischemia
      of a lower extremity. Twenty-one patients (57%) had three or more cardiovascular
      risk factors, and 22 (59%) had diabetes. Preoperative arteriography identified a
      pedal artery suitable for bypass in all but one patient. The greater or lesser
      saphenous vein was used in all patients, most frequently as a nonreversed,
      translocated vein graft. An arm vein was used as part of a composite graft in
      only one patient. No early deaths occurred, and only one patient had a
      perioperative myocardial infarction. Although five grafts occluded within 30
      days, four were successfully revised, and 36 patients had a patent graft at the
      time of dismissal from the hospital. At 1 year, the primary graft patency rate
      (patency without revision) was 60.8%, and the secondary patency rate was 68.8%.
      One early and six late amputations were performed; the cumulative 1-year limb
      salvage rate was 82.4%. Grafts with an intraoperative flow rate of 50 ml/min or
      more had a better patency rate than those with a lower flow rate. The presence of
      diabetes did not adversely affect long-term patency. Of the 34 patients who were
      alive at the time of this report, 27 (79%) had a functional foot that allowed
      ambulation, had no rest pain, and had no substantial loss of tissue. Pedal bypass
      should be considered for critical, chronic ischemia, even if the patient has an
      increased surgical risk and advanced distal atherosclerotic disease.

PMID- 2002683
TI  - Seizure-associated speech arrest in elderly patients.
AB  - Recurrent, brief episodes of speech arrest associated with bifrontal
      electroencephalographic seizure activity developed in three ill elderly patients.
      The seizures ceased after the initiation of antiepileptic drug therapy and the
      correction of metabolic abnormalities. The cause of the seizure activity remains
      unknown, but a possible mechanism may be a transient epileptogenic cortical
      dysfunction that predominantly affects the frontal lobes as a result of
      concomitant metabolic alterations.

PMID- 2002684
TI  - Serum lipids and lipoproteins are less powerful predictors of extracranial
      carotid artery atherosclerosis than are cigarette smoking and hypertension.
AB  - The effect of serum lipids and lipoproteins on extracranial carotid artery
      atherosclerosis (CAS) was studied in patients who underwent carotid
      arteriography. Serum lipid and lipoprotein values along with data on other
      potential predictors of extracranial CAS were determined in 240 patients who had
      at least one extracranial carotid artery visualized. In a multiple logistic
      regression analysis, the independently significant predictors of the presence of
      extracranial CAS were, in decreasing order of significance, duration of smoking
      of cigarettes, hypertension, age, and low-density lipoprotein cholesterol. Serum
      cholesterol, triglycerides, high-density lipoprotein cholesterol, and
      apolipoprotein A-I did not show an independent effect. Although low-density
      lipoprotein cholesterol was an independent predictor of the presence of
      extracranial CAS, its effect as a predictor was far outweighed by the effects of
      the duration of smoking of cigarettes and a history of hypertension.

PMID- 2002685
TI  - Early outcome after placement of a metallic intracoronary stent: initial Mayo
      Clinic experience.
AB  - After percutaneous transluminal coronary angioplasty, 3 to 7% of patients have in
      hospital coronary closure, and the risk of subsequent myocardial infarction is
      high, even with an urgent bypass operation. Disrupted coronary morphologic
      integrity, particularly with large dissections, may be associated with an
      increased risk of acute coronary closure. A percutaneously placed coronary
      vascular stent may rapidly alleviate acute or threatened coronary closure and
      could reduce morbidity. Between October 1989 and June 1990, placement of a
      balloon-expandable, flexible metallic coil (Gianturco-Roubin) coronary stent was
      attempted 16 times in 15 Mayo Clinic patients--for treatment of actual or
      threatened abrupt coronary closure in 10 patients, for primary treatment of a
      lesion judged to be at high risk for dissection with conventional balloon
      angioplasty in 1, and for elective treatment of restenotic lesions in 5.
      Placement of the stent was successful in 15 attempts (94%). Associated
      complications, which were uncommon, were similar to those noted after balloon
      angioplasty. No early deaths occurred, and no patient required coronary artery
      bypass grafting. Stents were successfully placed in both urgent and elective
      circumstances in native coronary arteries and saphenous vein grafts, and they
      were used in primary atheromatous and restenotic lesions. Our initial experience
      with this metallic coil stent indicates that it is efficacious for vascular
      disruption that is threatening or causing coronary closure after angioplasty.
      Furthermore, elective placement of a stent may be safely undertaken in patients
      with high-risk coronary lesions or recurrent restenotic lesions. The long-term
      outcome in all groups of patients who receive coronary stents is unknown.

PMID- 2002686
TI  - Efficacy of percutaneous mitral balloon valvuloplasty with the inoue balloon.
AB  - Percutaneous mitral balloon valvuloplasty has become an accepted technique for
      use in selected patients with severe, symptomatic mitral stenosis. Recently, a
      new balloon catheter with an "hourglass" shape and specially designed guidewires
      and dilators has become available (Inoue balloon). The design of this balloon
      provides ease of manipulation and self-stabilization across the mitral valve
      during inflation. These features should decrease the incidence of complications
      associated with the procedure. Preliminary results in 12 consecutive patients who
      underwent percutaneous mitral balloon valvuloplasty with the Inoue balloon are
      presented. The mitral valve area increased from 0.92 +/- 0.21 cm2 before the
      procedure to 1.75 +/- 0.40 cm2 after the procedure. No complications occurred
      from the procedure, including no increase in severity of mitral regurgitation or
      creation of an atrial septal defect. Further follow-up is necessary to determine
      the long-term efficacy with this new balloon. Nonetheless, the preliminary
      results are encouraging.

PMID- 2002687
TI  - Chromosome studies in 104 patients with polycythemia vera.
AB  - Chromosome studies were done in 104 patients with various stages of polycythemia
      vera (PV): 10 had leukemia-myelodysplastic syndrome, 28 had post-PV with myeloid
      metaplasia (PPVMM), 12 had PV with myelofibrosis, and 54 had PV. Chromosome
      studies were successful in 86 patients, 37 (43%) of whom had a chromosome
      abnormality. At diagnosis, 4 of 28 patients (14%) had an abnormal clone; the
      incidence was 78% in PPVMM and 100% in leukemia-myelodysplastic syndrome. Among
      the 63 patients with successful chromosome studies during the first 10 years of
      disease, 27% had an abnormal clone. In contrast, of the 23 patients who had the
      disease for more than 10 years, 87% had an abnormal clone. Chromosome
      abnormalities were found in 11 of the 60 patients who either were untreated or
      underwent only phlebotomy and in 26 of the 44 patients who were treated with
      myelosuppressive agents. Trisomy 8, +9, and 20q- were found in some patients
      early during the course of their disease and also among untreated patients. These
      chromosome abnormalities seem to be related to the natural course of PV rather
      than to therapy. Patients with a chromosomally abnormal clone at the time of
      diagnosis of PV had a poorer survival than did those with only normal metaphases.
      Cytogenetic results did not predict evolution of the disease, but they did
      provide clues to hematologic phenotype, duration of the disease, and consequences
      of myelosuppressive therapy.

PMID- 2002688
TI  - Plastic bronchitis: an old disease revisited.
AB  - Expectoration of bronchial casts (plastic bronchitis) is an uncommon but ancient
      problem. Herein we describe a 40-year-old man, with no prior lung disease, who
      had dyspnea, cough, and expectoration of long branching bronchial casts. No
      specific cause was delineated, although special stains for eosinophilic granule
      major basic protein demonstrated occasional foci of eosinophils and small amounts
      of extracellular major basic protein in the bronchial casts. Various diseases,
      such as allergic bronchopulmonary aspergillosis, bronchiectasis, and cystic
      fibrosis, have been associated with the formation of bronchial casts and should
      be considered in the differential diagnosis. Although most previously reported
      cases have been associated with some type of pulmonary disease, our patient had
      no evidence of an underlying pulmonary disorder.

PMID- 2002689
TI  - A coproporphyria-like syndrome induced by glipizide.
AB  - A 49-year-old man with a 1-month history of episodic, severe abdominal pain
      sought medical attention. The patient's history was remarkable for type II
      diabetes, for which glipizide therapy had been initiated 2 months earlier. No
      other medications were being taken at the time the paroxysms of pain began.
      During the episodes of pain, both examination of the abdomen and abdominal
      roentgenograms revealed normal findings. Initial assessment, including
      ultrasonography and computed tomographic scanning of the abdomen, upper
      gastrointestinal and colon roentgenograms, and esophagogastroduodenoscopy,
      revealed no cause of the pain. Empiric trials of famotidine, sucralfate, and
      antacids failed to relieve the pain. Both urine and fecal specimens collected
      after an attack demonstrated substantially increased coproporphyrins. The
      glipizide regimen was discontinued; 2 months later, the stool coproporphyrins had
      decreased to normal levels. At follow-up more than 1 year later, the patient had
      had no recurrence of abdominal pain. Although other orally administered
      hypoglycemic agents and other sulfa compounds have been reported to precipitate
      acute attacks of porphyria, to our knowledge this is the first such case
      associated with glipizide. We suggest that glipizide be added to the list of
      medications to be avoided in patients with porphyria.

PMID- 2002690
TI  - The Mayo legacy in medical education.

PMID- 2002691
TI  - Inframalleolar arterial reconstruction for limb salvage.

PMID- 2002692
TI  - Aphasia as the initial manifestation of epilepsy.

PMID- 2002693
TI  - Cigarette smoking, lipids, lipoproteins, and extracranial carotid artery
      atherosclerosis.

PMID- 2002694
TI  - Intracoronary stenting--hope or hype?

PMID- 2002695
TI  - Johns Hopkins--medical philanthropist.

PMID- 2002696
TI  - Longitudinal Gompertzian analysis of ischemic heart disease mortality in the
      U.S., 1962-1986: a method of demonstrating the deterministic dynamics describing
      its decline.
AB  - Age-adjusted mortality rates for ischemic heart disease (IHD) in the United
      States from 1962 to 1986 were subjected to longitudinal Gompertzian analysis. Age
      adjusted IHD mortality rate distributions between age 40 and 85 years were
      determined by a variable environmental factor and an extrapolated common
      intersect point. The environmental factor declined (improved) 3.73-fold for men
      and 2.07-fold for women in 1986 as compared to 1962. However, the environmental
      factor in 1986 remained 15.34 fold more conductive to IHD mortality among men
      than women. The age at the extrapolated common intersect point was 126.7 years
      for men and 267.4 years for women. Longitudinal Gompertzian analysis of IHD
      mortality data suggests that IHD will remain a significant cause of mortality for
      men despite advances in risk factor reduction and medical therapy.

PMID- 2002697
TI  - Species differences of elastic and collagenous tissue--influence of maturation
      and age.
AB  - Age-dependence of mechanical and biochemical parameters has been studied in
      pigeons between 1 and 80 months and in rats between 1 and 30 months. In pigeons,
      body weight, bone weight and breaking strength of femur and tibia are only
      slightly increased during this time indicating that in this species maturation
      takes place as early as during the first 4 weeks after hatching. In contrast, in
      rats a sharp increase of these parameters during maturation and a significant
      decrease during senescence was observed. Similarly, ultimate load of aorta rings
      was only sightly influenced by aging in pigeons, but showed in rats a biphasic
      pattern due to maturation and aging. The prepatagial tendon in pigeons gives the
      unique opportunity to study an organ consisting mostly of elastic fibres. Only a
      slightly increase of strength during the whole life-span, but no decrease during
      senescence was found. Tail tendons in rats consisting almost entirely of collagen
      fibres show a pronounced increase during maturation and a decrease during aging.
      The mechanical values were followed closely by the collagen content, but not at
      all by the elastin content.

PMID- 2002698
TI  - A new analysis of United Nations mortality statistics.
AB  - Demographic data published by the United Nations in 1987 are analysed in terms of
      the Gompertz function. Projections for maximum life spans are obtained, with the
      data broadly divisible into three clusters. These are attributable not only to
      the influence of high infant mortality, but suggest also constitutional and/or
      environmental variations among members of the clusters. The difference between
      life span and life expectancy is estimated analytically. A comparison with an
      earlier analysis supports the view that there are important differences between
      the life expectancies of the sexes.

PMID- 2002699
TI  - Regulation of the retinoblastoma anti-oncogene in aging human diploid
      fibroblasts.
AB  - Cell cycle expression of the retinoblastoma (RB) gene was investigated in young
      and aging IMR 90 human diploid fibroblasts and in the immortalized but
      untransformed A31 BALB/c 3T3 mouse fibroblasts. RB RNA levels increased about 75%
      during late G1/S in both the young and old IMR 90 cells. Young and old cells had
      similar normalized amounts of RB RNA per cell. Kinase C activation did not
      stimulate RB transcription. The A31 cells showed a constant RB RNA level
      throughout G0/S. The data is consistent with the hypothesis that RB activity is
      regulated primarily post-transcriptionally and indicates that a change in the
      regulation of RB transcription is not part of the senescence phenomenon.

PMID- 2002700
TI  - Effects of long-term, low-dose growth hormone therapy on immune function and life
      expectancy of mice.
AB  - We have studied effects of long-term, low-dose growth hormone therapy on the
      immune function and life expectancy of Balb/c mice. Sixty male Balb/c mice were
      aged up to the time when they started showing signs of senescence and causal
      death (deaths started when they became 17 months old). The aged mice were divided
      into two groups of 26 mice each. One group received growth hormone (30
      micrograms/mouse) subcutaneously twice a week for 13 weeks. The control group
      received an equal volume of saline for the same period. During this treatment
      period, 16 control mice died (61%) whereas only 2 of the hormone-treated mice
      died (7%). Four mice from each group were killed and immunological functions of
      splenocytes were evaluated. Hormone-treated mice had higher stimulation indices
      for pokeweed mitogen but not for Concanavalin-A. Total IgG production was
      decreased but IL-1, IL-2 and TNF production was increased. After a lag period of
      4 weeks, growth hormone therapy was continued for another 6 weeks. One of the
      growth hormone treated mice died while the control group no longer existed.
      Splenocyte functions of the growth hormone treated mice were compared to those of
      young mice. The results showed no significant difference between cytokine
      production (IL-1, IL-2, TNF and IgG) in the young and the hormone treated groups.
      Stimulation induced by concanavalin-A and pokeweed mitogen however, was higher in
      the young group than the old group. The mortality curve obtained suggests that
      long-term low-dose growth hormone treatment prolongs life expectancy.

PMID- 2002701
TI  - [The abortion law is doubted by new routines for taking care of the fetus after
      abortion].

PMID- 2002702
TI  - [Transillumination or mammography in diagnosis of breast cancer?].

PMID- 2002703
TI  - [Drug prevention of malaria. No regime gives a complete protection].

PMID- 2002705
TI  - [Laser or a conventional method. The same cosmetic result].

PMID- 2002704
TI  - [Answers to an inquiry. Many women prefer transillumination to mammography].

PMID- 2002706
TI  - [Cervical manipulation--a hazardous therapy when performed by unskilled hands].

PMID- 2002707
TI  - [Difficulties with drug administration to children. Why not suppositories?].

PMID- 2002708
TI  - [A study circle is better than a health resort--a comparison between dieting
      methods].

PMID- 2002709
TI  - [WHO reevaluates malaria prevention: revision of earlier recommendations is
      justified by resistance development].

PMID- 2002710
TI  - [Fatal cases of malaria--preventive recommendations and information to
      travellers].

PMID- 2002711
TI  - [Wrong grading of care needs forces the patients with dementia to unnecessary
      transfers].

PMID- 2002712
TI  - [New methods accelerate the development of thrombolytic agents].
AB  - Owing to the possible involvement of impaired fibrinolytic function in venous and
      arterial thrombotic disorders, and the benefit of thrombolytic treatment in the
      acute stage of myocardial infarction, the fibrinolytic system has attracted
      increasing interest. In this brief review are discussed recent advances in our
      knowledge of the regulation of fibrinolysis and the effect in thrombolytic
      disorders of impaired tissue plasminogen activator release and increased
      concentrations of the endothelial cell-related plasminogen activator inhibitor.
      PAI-1. Also discussed are the molecular basis of effective and specific
      thrombolytic treatment and progress in the search for and development of new,
      primarily recombinant, fibrin-specific plasminogen activators.

PMID- 2002713
TI  - [Posterior proctotomy--a therapeutic alternative in benign rectal tumors].

PMID- 2002714
TI  - [The men behind the method. George Caldwell and Henri Luc. They introduced a more
      radical surgical technique for evacuation of maxillary sinus abscesses].

PMID- 2002715
TI  - [Mediastinal irradiation--a risk factor of heart disease].

PMID- 2002716
TI  - [An anti-inflammatory substance explains the tissue compatibility of titanium?].

PMID- 2002717
TI  - [A pilot project: the quality of continuing medical education can be measured by
      inquiry or inspection].

PMID- 2002718
TI  - [A research project in Gothenburg: bone-anchored prostheses for hip, knee and
      knuckle].

PMID- 2002719
TI  - [Is future hip joint prosthesis a hybrid? Prostheses for other joints are badly
      needed].

PMID- 2002720
TI  - [Does screening influence mortality of colorectal cancer?].

PMID- 2002721
TI  - [Radiology ought to be done by specialists. Cooperation with clinics a matter of
      course].

PMID- 2002722
TI  - [Await results from studies on celiac disease before dietary recommendations are
      changed].

PMID- 2002723
TI  - [Assessment of quality in vascular surgery--5-years experience of a routine care
      procedure].

PMID- 2002724
TI  - [Psychopedagogic programs improves family support in schizophrenia].

PMID- 2002725
TI  - [Non-smoking women regardless of age, may use modern oral contraceptives].

PMID- 2002726
TI  - [Helicobacter pylori and chronic ulcer disease].

PMID- 2002727
TI  - [A lump in the thyroid gland can be tuberculosis].

PMID- 2002728
TI  - [Psychodynamic psychotherapy research--methodological questions].

PMID- 2002729
TI  - [Social and socioeconomic review. Which women seek help for alcohol problems, and
      which get good results?].

PMID- 2002730
TI  - [The man behind the drug. Peter Forsskal: the father of the forskolin. Linne's
      disciple who died hunting for unknown plants on an expedition in "Prosperous
      Arabia"].

PMID- 2002731
TI  - [Ernst Josephson of current interest in a film and rediscovered sketches. There
      is no schizophrenic art, only art done by schizophrenic artists].

PMID- 2002732
TI  - [Molecular genetics--valuable diagnostic complement in cases of
      lymphomas/leukemias].

PMID- 2002733
TI  - [Hemorrhagic complication to portal hypertension--an assessment of therapeutic
      alternatives].

PMID- 2002734
TI  - [Can primary health care solve the health care crisis?].

PMID- 2002735
TI  - [Scandinavian unity on MBD assessment. The term is old-fashioned and unsuitable].

PMID- 2002736
TI  - [The Sydney system--a new, many-sided classification of gastritis].

PMID- 2002737
TI  - [The choice of surgical method should be based on patients' demands and
      conditions].

PMID- 2002738
TI  - [Development of therapy and diagnosis in gastroenterology in Scandinavia].

PMID- 2002739
TI  - [Spinal cord stimulation in chronic neuropathic pain].
AB  - Seventeen years' experience of spinal cord stimulation in the treatment of
      chronic pain has shown it to be effective only in the case of neuropathic pain-
      in particular, pain due to lesions in peripheral nerves or posterior roots. In
      such cases, pharmacological treatment is often unsuccessful, and transcutaneous
      electrical nerve stimulation is only useful in certain cases. In a retrospective
      study of 84 patients followed for up to 16 years, 56 patients were still using
      their stimulators and reported continued pain relief. The majority suffered from
      peripheral neuralgia due to trauma or surgery and 72 per cent in that group
      enjoyed satisfactory relief. Trial stimulation via a temporary extension lead for
      at least 4-5 days is a prerequisite of good long-term results. It is concluded
      that spinal cord stimulation is an indispensable tool for treating chronic
      neuropathic pain, and it merits to be used more frequently.

PMID- 2002740
TI  - [Garlic and olive oil: good in food but unsuitable for skin care].

PMID- 2002741
TI  - [A closed system for bladder drainage via an indwelling catheter reduces the
      risks of bacteriuria].

PMID- 2002742
TI  - [Suicide and biological markers].

PMID- 2002743
TI  - [How do biological characteristics increase the risk of suicide?].

PMID- 2002744
TI  - [Psychiatric consultation for health and drug insurance: suicide is a majority
      among the relatively few cases entitled to compensation].

PMID- 2002745
TI  - [New guidelines from the National Board of Health and Welfare: to prevent suicide
      within the health care services].

PMID- 2002746
TI  - Transforming growth factor (TGF)-alpha in human milk.
AB  - Transforming growth factor (TGF)-alpha and epidermal growth factor (EGF) were
      measured in human milk by means of homologous radioimmunoassay. As previously
      reported, EGF concentration in the colostrum was approximately 200 ng/ml and
      decreased to 50 ng/ml by day 7 postpartum. The value of immunoreactive (IR)-TGF
      alpha was 2.2-7.2 ng/ml, much lower than that of EGF. In contrast to EGF, the
      concentration of IR-TGF-alpha was fairly stable during the 7 postpartum days.
      There was no relationship between the concentrations of IR-TGF-alpha and IR-EGF,
      suggesting that the regulatory mechanism in the release of the two growth factors
      is different. On gel-chromatography using a Sephadex G-50 column, IR-EGF appeared
      in the fraction corresponding to that of authentic human EGF, while 70%-80% of
      the IR-TGF-alpha was eluted as a species with a molecular weight greater than
      that of authentic human TGF-alpha. Although the physiological role of TGF-alpha
      in milk is not known, it is possible that it is involved in the development of
      the mammary gland and/or the growth of newborn infants.

PMID- 2002747
TI  - Morphine-6-glucuronide contributes to rewarding effects of opiates.
AB  - It was recently confirmed that a metabolite of morphine, morphine-6-glucuronide
      (M6G), is a long lasting, powerful analgesic in humans and animals and may
      account for a major component of clinical opiate analgesia. It is reported here
      that M6G is also a powerful behavioral reinforcer in the conditioned place
      preference test in rats, indicating that it has rewarding properties, and is
      therefore likely to have abuse potential. The induction of a place preference by
      M6G is blocked by naltrexone, indicating that the rewarding effect of M6G is
      mediated by opioid receptors. Given systemically M6G is approximately equipotent
      with morphine. When given intracerebroventricularly to bypass the blood-brain
      barrier, M6G is 146 times more potent than morphine in the place preference test.
      Thus 6-substituted metabolites of opiates may play a more significant role in the
      effects of opiates than has been previously assumed.

PMID- 2002748
TI  - Effects of tobacco smoke constituents on MPTP-induced toxicity and monoamine
      oxidase activity in the mouse brain.
AB  - Exposure to cigarette smoke has been found to attenuate the reduction in striatal
      dopamine levels caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in
      mice and to inhibit monoamine oxidase (MAO) activity in brain tissue. To confirm
      whether specific smoke constituents which have been reported to protect against
      MPTP toxicity were responsible for these effects, mice were treated chronically
      with nicotine, 4-phenylpyridine and hydrazine. Although all three compounds
      prevented the decrease in dopamine metabolite levels induced by MPTP, there was
      no significant effect on dopamine levels. None of the three compounds inhibited
      MAO activity in cerebral tissue following treatment in vivo. However, an extract
      of tobacco smoke particulate matter caused a marked inhibition of MAO A and MAO B
      activity when added in vitro. The results suggest that one or more unidentified
      substances in tobacco smoke are capable of inhibiting brain MAO and perhaps
      altering the formation of the active metabolite of MPTP.

PMID- 2002749
TI  - Prolactin messenger ribonucleic acid concentrations throughout the ovine estrous
      cycle: assessment relative to prolactin serum and pituitary amounts.
AB  - Prolactin (PRL) mRNA concentrations were assessed by nucleic acid hybridization
      assays in pituitaries of ewes representing the defined stages of the ovine
      estrous cycle. Concomitantly, pituitary and serum PRL concentrations were
      measured in these ewes using radioimmunoassays. It was observed that PRL serum,
      pituitary and mRNA concentrations tended to increase near the time of the
      gonadotropin preovulatory surge, particularly between 24 hrs before behavioral
      estrus to 5 hours after estrus. However, the changes in PRL mRNA, serum and
      pituitary concentrations were shown not to be statistically significant. These
      data suggest that PRL production during the sheep estrous cycle is maintained
      without dramatic changes in synthesis or secretion.

PMID- 2002750
TI  - The influence of alpha-fluoromethylhistidine and histamine receptor antagonists
      on the beta-endorphin-induced corticosterone response.
AB  - Involvement of a central histaminergic mechanism in the stimulating effect of
      beta-endorphin (beta-End) on the pituitary-adrenocortical activity, measured
      indirectly through corticosterone secretion, was investigated in conscious rats.
      The rise in serum corticosterone levels, induced by beta-End injected
      intraventricularly (icv) was considerably impaired by pretreatment with
      naltrexone, an opioid receptor antagonist. The stimulating effect of beta-End was
      almost totally suppressed by a prior icv administration of mepyramine, a
      histamine H1-receptor antagonist, and also considerably reduced by pretreatment
      with cimetidine, an H2-receptor antagonist. The strongest suppression, by 83%; of
      the beta-End-induced corticosterone response was evoked by a prior administration
      of alpha-fluoromethylhistidine, an inhibitor of neuronal histamine synthesis in
      the brain. These results indicate that both the brain neuronal histamine and
      central histamine H1- and H2-receptors are considerably involved in the beta
      endorphin-induced stimulation of the pituitary-adrenocortical activity.

PMID- 2002751
TI  - Time-dependent biphasic effect of cytochalasin D on luteal progesterone release
      in the pregnant rat.
AB  - Numerous studies have examined the effects of cytoskeletal disruption on
      steroidogenesis; while some report an inhibition, other studies show a
      stimulation of steroid hormone production. In the present study, the possibility
      of a biphasic effect of cytoskeletal inhibitors on steroidogenesis was examined.
      Luteal tissue from day 12 pregnant rats was incubated for either 3.5 h (short
      term) or 12.5 h (long-term) with cytochalasin D or colchicine at 10(-4) M in
      Medium 199 (medium). Controls were incubated in medium alone. After the
      incubation, the tissues were separated from the medium, and either processed for
      electron microscopy, or weighed and snap-frozen for subsequent homogenization and
      steroid hormone measurements. Progesterone, testosterone, and 17 beta-estradiol
      levels in the medium were measured by radioimmunoassay. After the short-term
      incubation, progesterone release decreased with cytochalasin D treatment, while
      cells became more rounded in shape with a loss of microfilaments. Upon long-term
      incubation, progesterone release increased and cell contact lessened. Colchicine
      had no effect at either incubation time, and estradiol and testosterone
      production remained unchanged throughout the experiments. These results
      demonstrate that cytochalasin D has a biphasic effect on luteal progesterone
      release in the rat and provides an explanation for the dichotomy of results thus
      far reported. In addition, the effects of cytochalasin D on rat luteal
      progesterone production appear to be the result of changes in cell shape or cell
      to-cell contact.

PMID- 2002752
TI  - Detection of site-specific binding and co-binding of ligands to macromolecules
      using 19F NMR.
AB  - Study of ligand-macromolecular interactions by 19F nuclear magnetic resonance
      (NMR) spectroscopy affords many opportunities for obtaining molecular biochemical
      and pharmaceutical information. This is due to the absence of a background
      fluorine signal, as well as the relatively high sensitivity of 19F NMR. Use of
      fluorine-labeled ligands enables one to probe not only binding and co-binding
      phenomena to macromolecules, but also can provide data on binding constants,
      stoichiometries, kinetics, and conformational properties of these complexes.
      Under conditions of slow exchange and macromolecule-induced chemical shifts,
      multiple 19F NMR resonances can be observed for free and bound ligands. These
      shifted resonances are a direct correlate of the concentration of ligand bound in
      a specific state rather than the global concentrations of bound or free ligand
      which are usually determined using other techniques such as absorption
      spectroscopy or equilibrium dialysis. Examples of these interactions are
      demonstrated both from the literature and from interactions of 5
      fluorotryptophan, 5-fluorosalicylic acid, flurbiprofen, and sulindac sulfide with
      human serum albumin. Other applications of 19F NMR to study of these interactions
      in vivo, as well for receptor binding and metabolic tracing of fluorinated drugs
      and proteins are discussed.

PMID- 2002753
TI  - Accumulation of polycyclic aromatic hydrocarbon-induced single strand breaks is
      attributed to slower rejoining processes by DNA polymerase inhibitor, cytosine
      arabinoside in CHO-K1 cells.
AB  - We demonstrate a successful induction of DNA single strand breaks in CHO-K1 cells
      by cocultivation with mouse embryonic fibroblasts (MEF) during exposure to
      benzo(a)pyrene (BP) or 3-methylcholanthrene (MC). When compared to those induced
      by methyl methanesulfonate (MMS), the DNA single strand breaks induced by BP and
      MC were markedly accumulated by post-incubation with cytosine arabinoside (araC)
      and were much more delayed in their rejoining. These results suggest that the
      active metabolites of BP or MC produced by cocultivation with MEF or microsomal
      fraction (S-15) result in the formation of large DNA adducts which require an
      active participation of DNA polymerase alpha(delta) in the polymerization step of
      excision repair for their removal.

PMID- 2002754
TI  - Repeated stressful experiences differently affect brain dopamine receptor
      subtypes.
AB  - The binding of tritiated spiperone (D2 antagonist) and tritiated SCH 23390 (D1
      antagonist), in vivo, was investigated in the caudatus putamen (CP) and nucleus
      accumbens septi (NAS) of mice submitted to ten daily restraint stress sessions.
      Mice sacrificed 24 hr after the last stressful experience presented a 64%
      decrease of D2 receptor density (Bmax) but no changes in D1 receptor density in
      the NAS. In the CP a much smaller (11%) reduction of D2 receptor density was
      accompanied by a 10% increase of D1 receptors. These results show that the two
      types of dopamine (DA) receptors adapt in different or even opposite ways to
      environmental pressure, leading to imbalance between them.

PMID- 2002755
TI  - Depression of the cat cortical visual evoked potential by soman.
AB  - The effects of intravenous administration of the anticholinesterase agent soman
      (pinacolyl methylphosphonofluoridate, 3-15 micrograms/kg) on the visual evoked
      potential (VEP) were examined in cats using phase-reversed sine wave grating
      stimuli of different spatial frequencies and contrasts. Doses of 5-7
      micrograms/kg caused a depression of the VEP across all spatial frequencies in an
      abrupt, non-graded fashion. Studies in which contrast was varied showed that VEP
      depression resulted primarily from a decrease in the system gain rather than a
      change in the contrast sensitivity, and that response depression increased with
      increasing contrast. The dominant changes in gain revealed by these studies are
      consistent with a modulation of potassium conductance in the cell membrane which
      previous studies have shown to be dependent on a cholinergic mechanism.

PMID- 2002756
TI  - Pretreatment with physostigmine, mecamylamine and atropine reduces the impact of
      soman on the cortical visual evoked potential of the cat.
AB  - A pretreatment regimen of physostigmine, mecamylamine and atropine was evaluated
      for its ability to alleviate the impact of soman on visual system function as
      measured by changes in the cortical visual evoked potential (VEP) of the cat.
      Data from unprotected animals showed a threshold (30% depression in the VEP) of
      6.4 micrograms/kg, while in pretreated animals, the threshold dose was 32.7
      micrograms/kg, yielding a protection ratio of 5:1. Extending the time between
      pretreatment and exposure reduced the degree of protection. Pretreatment also
      reduced the degree of VEP depression at suprathreshold doses, indicating a
      therapeutic effect even in cases of severe exposure.

PMID- 2002757
TI  - Differential effects of emotional and physical stress on the central and
      peripheral secretion of neurohypophysial hormones in male rats.
AB  - The effects of various stressful conditions on the levels of oxytocin (OT) and
      vasopressin (VP) in plasma and cisternal cerebrospinal fluid (CSF) of male rats
      were investigated. Three experimental models were used: exposure to a novel
      environment for 5 min, immobilization for 15 min, and ether inhalation for 10 min
      resulting in anaesthesia. Novelty and immobilization induced a slight but
      significant increase in OT levels in the CSF immediately after the stress. The
      effect of ether was considerably more pronounced. The concentration of VP in the
      CSF was elevated only by ether stress. In plasma, the level of OT was increased
      immediately following immobilization and ether stress but not after novelty
      stress, whereas VP only showed a delayed response 20 min after immobilization.
      These results indicate a rapid preferential release of OT in the periphery in
      response to physical and pharmacological stress. In addition, they provide
      evidence that release of OT into the CSF is triggered by physical,
      pharmacological as well as emotional stress, while the central release of VP is
      rather resistant to emotional stress. The data suggest that OT is a stress
      hormone in the central nervous system.

PMID- 2002758
TI  - Blockade of behavioral sensitization to methamphetamine by lesion of hippocampo
      accumbal pathway.
AB  - The present studies were carried out to explore a role of the hippocampal
      efferents in the development of the locomotor augmentation induced by repeated
      methamphetamine administrations. For this purpose, electrolytic lesions of either
      the dorsal fornix or the fimbria fornix were made bilaterally in rats. The latter
      treatment, not the former, blocked the behavioral sensitization. These results
      suggest that the hippocampo-accumbal pathway may play an important role in the
      development of the sensitization.

PMID- 2002759
TI  - Nifedipine and verapamil block the memory-facilitating effect of corticotropin
      releasing factor in rats.
AB  - The effects of two calcium channel blockers, nifedipine and verapamil, and the
      peptide corticotropin releasing factor (CRF) as well as their interactive effects
      on memory retention were examined in rats. Male Sprague-Dawley rats were
      chronically cannulated bilaterally and drugs were directly injected into the
      dentate gyrus of the hippocampus. Animals were trained in a one-way inhibitory
      avoidance task and memory was measured 24 h later. Results indicate that there
      was a U-shaped dose-response curve for the effects of nifedipine and verapamil
      with nifedipine at 8 micrograms and verapamil at 1 microgram both impaired memory
      formation, while CRF at 0.1 microgram enhanced this process. Nifedipine at 2
      micrograms and verapamil at 0.5 microgram, which did not have significant effects
      on memory by themselves, antagonized the memory-enhancing effect of CRF in the
      hippocampus. These results suggest that under normal physiological conditions,
      calcium influx may play an important role in memory consolidation process in the
      vertebrate.

PMID- 2002760
TI  - Subfamily relationships and clustering of rabbit C repeats.
AB  - C repeats constitute the predominant family of short interspersed repeats (SINEs)
      in the rabbit genome. Determination of the nucleotide sequence 5' to rabbit zeta
      globin genes reveals clusters of C repeats, and analysis of these and other
      sequenced regions of rabbit chromosomes shows that the C repeats have a strong
      tendency to insert within or in close proximity to other C repeats. An alignment
      of 44 members of the C repeat family shows that they are composites of different
      sequences, including a tRNA-like sequence, a conserved central core, a stretch of
      repeating CT dinucleotides, and an A-rich tract. Cladograms generated by both
      parsimony and cluster analysis subdivide the C repeats into at least three
      distinct subfamilies. Nucleotides at sites diagnostic for subfamilies appear to
      have changed in a punctuated and progressive manner during evolution, indicating
      that a limited number of progenitors have given rise to new repeats in waves of
      dispersion. C repeats that insert into preexisting C repeats belong to
      subfamilies that are proposed to have been propagated more recently; hence, these
      data support the model of dispersion in successive waves. The divergence among
      the oldest group of C repeats is greater than that observed for the analogous Alu
      repeats in humans, indicating that rabbit C repeats have been propagating longer
      than human Alu repeats. The improved consensus sequence for these repeats is
      similar to that of the predominant artiodactyl SINE in both the tRNA-like region
      and a central region. Because members of different subfamilies cross-hybridize
      very poorly, hybridization data with representatives of each subfamily provide a
      new minimal estimate, 234,000, for the copy number of C repeats in the rabbit
      haploid genome, although it is likely that the actual value is closer to 1
      million.

PMID- 2002761
TI  - The relative rate of DNA evolution in primates.
AB  - In 73 relative-rate tests involving the sequences of 17 genes between humans and
      six nonhuman primate taxa, there is only one significant (P less than 0.01)
      difference in evolutionary rate--i.e., that between human and Old World-monkey
      psi eta-globin genes. No evolutionary rate difference between humans and Old
      World monkeys is evident from analysis of 18 other genes with a total length of 6
      kb. This and the comparison, between humans and other primate taxa, of new
      extended psi eta-globin sequences suggest that earlier observations of
      evolutionary-rate differences between humans and other primates were based on
      differences that are peculiar to psi eta-globin and that are not representative
      of the whole genome, which appears to be evolving at a stochastically uniform
      rate. This is supported by whole-genome single-copy DNA and mitochondrial DNA
      comparisons, neither of which shows any evidence of evolutionary-rate variation
      among primate taxa. Uniformity in the evolutionary rate of the DNA of primate and
      other mammalian taxa is inconsistent with current mammalian fossil-record
      interpretation. Either there has been a general slowing down in rate across
      lineages or the fossil record has been misinterpreted.

PMID- 2002762
TI  - Methods for inferring phylogenies from nucleic acid sequence data by using
      maximum likelihood and linear invariants.
AB  - Likelihood methods and methods using invariants are procedures for inferring the
      evolutionary relationships among species through statistical analysis of nucleic
      acid sequences. A likelihood-ratio test may be used to determine the feasibility
      of any tree for which the maximum likelihood can be computed. The method of
      linear invariants described by Cavender, which includes Lake's method of
      evolutionary parsimony as a special case, is essentially a form of the likelihood
      ratio method. In the case of a small number of species (four or five), these
      methods may be used to find a confidence set for the correct tree. An exact
      version of Lake's asymptotic chi 2 test has been mentioned by Holmquist et al.
      Under very general assumptions, a one-sided exact test is appropriate, which
      greatly increases power.

PMID- 2002763
TI  - Drosophila glucose dehydrogenase and yeast alcohol oxidase are homologous and
      share N-terminal homology with other flavoenzymes.

PMID- 2002764
TI  - Studies on the phylogenetic position of the Ctenodactylidae (Rodentia)

PMID- 2002765
TI  - Rates of DNA change and phylogeny from the DNA sequences of the alcohol
      dehydrogenase gene for five closely related species of Hawaiian Drosophila.
AB  - The sequence of 1.6 kb of DNA surrounding the alcohol dehydrogenase (Adh) gene
      from five species of the Planitibia subgroup of the Hawaiian picture-winged
      Drosophila, with estimated divergence times of 0.4-5.1 Myr, has been determined.
      The gene trees which were found by using the sequence divergence from different
      regions of the sequences are generally in accord with the phylogeny proposed for
      these species when chromosomal inversions and island of origin are used. One of
      the species (D. picticornis) appears to be more distant from the other species in
      this group than they are from a member of the Grimshawi group (D.
      affinidisjuncta) which is chromosomally more distant. Two of the species (D.
      differens and D. plantibia) show heterogeneity in the nucleotide changes in the
      Adh coding region, heterogeneity which is interpreted to be due to a gene
      conversion or recombination after hybridization between the two species. The
      minimal rate of nucleotide substitution of synonymous nucleotides and of
      nontranscribed nucleotides downstream from the coding region is estimated as 1.5
      x 10(-8) and 1.1 x 10(-8) substitutions/nucleotide/year, respectively. This rate
      is two to three times the maximal rate estimated for mammalian synonymous
      substitutions.

PMID- 2002766
TI  - Ribosomal DNA variation within and between species of rodents, with emphasis on
      the genus Onychomys.
AB  - Patterns of restriction-endonuclease site and length variation at the nuclear
      rDNA locus (18S + 28S rRNA gene complex) were examined in rodents. Of the 164
      restriction sites mapped for seven species, 22 were conserved (mapping to the
      18S, 28S, and 5.8S genes and ITS1) in all three Onychomys species as well as in
      Mus musculus and in three closely related peromyscine rodents, Peromyscus boylii,
      P. eremicus, and Reithrodontomys megalotis. The nontranscribed spacer (NTS)
      region revealed most of the variation among these taxa, with the patterns of
      variation grouping into the following categories, (1) intraindividual variation
      revealing as many as four site-specific repeat types within an individual, (2)
      intraspecific and interspecific site variation confined to the NTS, and (3)
      length variation in both the transcribed and NTS regions. Length variation in the
      28S rRNA gene was also examined in 17 additional rodent species, and most size
      differences mapped to the divergent domain, D8, found in sequence comparisons
      between Mus and Rattus. The systematic implications of rDNA variation are
      discussed using the perspective gained from these rodent comparisons.

PMID- 2002768
TI  - They call it Fort Wood.

PMID- 2002767
TI  - Variation in mitochondrial cytochrome b sequence in natural populations of South
      American akodontine rodents (Muridae: Sigmodontinae).
AB  - A 401-bp fragment of the mitochondrial cytochrome b gene was sequenced from
      polymerase chain reaction-amplified products for 20 natural populations
      representing 12 species of South American akodontine rodents (Muridae). Variation
      among these taxa increased with their hierarchical position, from comparisons
      within local populations to those among different genera. Two individuals from
      the same local population differed by less than 1% sequence divergence. Sequence
      divergence among geographic samples within a species was 0.25%-8%, while that
      among species was 3%-21%. Comparisons of the akodontine sequences with that for
      the house mouse show 21%-25% sequence difference. A parsimony-based phylogenetic
      analysis of the data supports the placement of the taxon Microxus within Akodon
      (sensu stricto), of Bolomys just outside the Akodon cluster, and of Chroeomys as
      a separate genus quite distinct from the other members of this group. This
      phylogenetic hypothesis is identical to that determined from electrophoretic data
      but is quite divergent from the present taxonomy of the group.

PMID- 2002769
TI  - Theoretical and empirical approaches to protein-structure prediction and
      analysis.

PMID- 2002770
TI  - Fluorescence techniques for studying protein structure.

PMID- 2002771
TI  - The use of monoclonal antibodies and limited proteolysis in elucidation of
      structure-function relationships in proteins.

PMID- 2002772
TI  - Protein-ligand interaction as a method to study surface properties of proteins.

PMID- 2002773
TI  - WSU to participate in national AIDS study.

PMID- 2002774
TI  - State agency heads call for physician input on environment's health effects.

PMID- 2002775
TI  - History of Michigan medicine and other MSMS journals.

PMID- 2002776
TI  - A closer look at MSMS' health insurance program.

PMID- 2002777
TI  - Alternative forms of dispute resolution--we must be clear on what we want.

PMID- 2002778
TI  - Readers would benefit from hearing dissenting view of low level radioactive
      wastes compact.

PMID- 2002779
TI  - "The midwife as practitioner." Successful practice--can we do it?

PMID- 2002780
TI  - Independent midwifery--filling the gaps and picking up the pieces.

PMID- 2002781
TI  - Midwifery with a difference.

PMID- 2002782
TI  - Drugs of choice for cancer chemotherapy.

PMID- 2002783
TI  - BCG for bladder cancer.

PMID- 2002785
TI  - Safe needles.

PMID- 2002784
TI  - Alprazolam for panic disorder.

PMID- 2002786
TI  - Access to health care and the year 2000 objectives.

PMID- 2002787
TI  - Medical schools seek ethnic & cultural diversity.

PMID- 2002788
TI  - Transvaginal versus transabdominal sonography in patients suspected of having
      ectopic pregnancy.
AB  - To determine the value of transvaginal sonography in the evaluation of women with
      suspected ectopic pregnancy, we retrospectively studied 47 pregnant patients in
      whom both conventional transabdominal sonography (TAS) and transvaginal
      sonography (TVS) had been performed. Each patient had been given a standard TAS
      examination with the bladder moderately distended. After voiding, a TVS
      examination was performed. TAS and TVS were compared for their ability to reveal
      specific sonographic findings, including the double decidual sac sign, yolk sac,
      embryonic pole, and embryonic heart activity. Results indicate that the important
      sonographic findings of early pregnancy are more likely to be seen transvaginally
      than transabdominally. In 23% of the patients, only TVS provided the findings for
      diagnosis of the location and status of the pregnancy. In another 22%, the
      information gathered through TVS allowed increased confidence in the diagnostic
      accuracy of the TAS findings by providing additional findings. Therefore, in 45%
      of the cases, TVS influenced clinical decision-making. In no case was TVS less
      informative than TAS. These results support the claim that TVS contributes to
      diagnostic accuracy in early pregnancy. TVS should usually be used in conjunction
      with, and not as a substitute for, TAS. TVS is best used when TAS is not
      conclusive, or when immediate confirmation of an intrauterine pregnancy is
      desired.

PMID- 2002789
TI  - Investing in bonds.

PMID- 2002790
TI  - MMA responds to Access Commission proposals.

PMID- 2002791
TI  - AIDS findings.

PMID- 2002792
TI  - AIDS vaccine.

PMID- 2002793
TI  - Bringing equity and balance to health care access.

PMID- 2002794
TI  - At the center of health care access reform. Interview by A. Stuart Hanson.

PMID- 2002795
TI  - Professor John J. Roberts 1926-1990.

PMID- 2002796
TI  - A cytogenetic follow-up study of the victims of a radiation accident in Goiania
      (Brazil).
AB  - A radiation accident involving a cesium-137 therapy source occurred in Goiania
      (Brazil) in September 1987, in which more than 50 individuals were exposed to
      moderate to high doses (0.2-7 Gy) of gamma-radiation. A cytogenetic technique
      (i.e., frequencies of dicentrics and rings in peripheral lymphocytes) was
      employed to estimate the absorbed radiation dose. The follow-up study extending
      over more than 1 year indicated a decline in the frequencies of dicentrics in the
      lymphocytes. Using chromosome-specific biotinylated library probes for
      chromosomes 1, 2, 8 and 19, we studied the frequencies of chromosomal
      translocations and deletions and the incidence of aneuploidy in the lymphocytes
      of exposed individuals. In some individuals there was a significant increase in
      the frequency of translocations and aneuploidy. In other experiments, in which
      the frequencies of HPRT mutations were determined in lymphocytes using the BrdU
      labeling method, some individuals showed an increase (from about 2- to 50-fold)
      in mutant frequencies.

PMID- 2002797
TI  - DNA-expressed human cytochrome P450s: a new age of molecular toxicology and human
      risk assessment.
AB  - It has long been recognized that a large degree of species differences exists
      among drug and carcinogen metabolizing enzymes. In particular, differences in
      cytochrome P450s, the principal enzymes of metabolic activation of
      procarcinogens, are widespread and may determine species and individual
      susceptibility to cancer causing chemicals. Although species differences in both
      the regulation and catalytic activities of P450s are quite large, roden-based
      systems are mainly used as the means to determine the degree of hazard of
      environmental pollutants, pesticides, drugs and other environmental chemicals to
      humans. During recent years, a large effort has been expended on analyzing
      directly the structure, properties and catalytic activities of P450s from human
      tissues. In vitro mutagen testing systems, based on activation by human P450s,
      are being developed that will supplement other test systems in order to more
      accurately predict human risk to chemical exposure.

PMID- 2002798
TI  - Cytogenetic effects of pulsing electromagnetic field on human lymphocytes in
      vitro: chromosome aberrations, sister-chromatid exchanges and cell kinetics.
AB  - Exposure of human lymphocyte cultures to a pulsing electromagnetic field (PEMF;
      50 Hz, 1.05 mT) for various durations (24, 48 and 72 h) resulted in a
      statistically significant suppression of mitotic activity and a higher incidence
      of chromosomal aberrations. Furthermore, the shorter exposure times (24 and 48 h)
      did not cause a significant delay in cell turnover (cell proliferation index) or
      an increase in the baseline frequency of sister-chromatid exchanges (SCE).
      However, cultures continuously exposed to PEMF for 72 h exhibited significant
      reduction of the cell proliferation index (CPI) and an elevation of SCE rate.
      These results suggest that exposure to PEMF may induce a type of DNA lesions that
      lead to chromosomal aberrations and cell death but not to SCE, except probably at
      longer exposure times.

PMID- 2002799
TI  - Premature onset of mitosis and potentiation of chromosome damage induced by poly
      D-lysine in plant cells: evidence for G2 repair.
AB  - Poly-D-lysine has been reported to induce a triggering of mitosis in plant cells
      due to a selective stimulatory effect on cells arrested in G2. Root-tip cells of
      Allium cepa L. were first exposed to maleic hydrazide (MH) early in the cell
      cycle and posttreated with different concentrations of the polycationic agent
      while in G2. The result was a dose-dependent potentiation of chromosome damage
      observed at metaphase without any apparent effect induced by poly-D-lysine
      itself. The enhancement of the yield of chromosomal aberrations was concomitant
      with an increase in the frequency of mitosis. In order to test further the
      stimulatory effect of poly-D-lysine on mitosis, as well as the consequences of a
      shortening of the time available for repair, cells synchronized by protracted
      treatment with 5-aminouracil (5-AU), which also induces chromosome damage, were
      allowed to recover in the presence of the polycationic compound. Our data show
      that a premature arrival at mitosis resulted in an increase in the frequency of
      damaged cells observed.

PMID- 2002800
TI  - Arylamine activation following chronic ethanol ingestion by rats: studies on the
      liver S9, microsomal and cytosolic fractions and comparison with Aroclor 1254
      pretreatment.
AB  - That enzyme fractions derived from animals chronically fed alcohol can alter the
      metabolism of carcinogenic xenobiotic compounds has been documented. To further
      understand this relationship the mutagenicity of 3 aromatic amines was determined
      in the Ames test, employing activation systems derived from rats maintained on an
      alcohol-containing liquid diet, an isocaloric control liquid diet or Aroclor 1254
      pretreated animals fed standard laboratory chow. Depending upon protein and
      substrate concentrations, S9 from ethanol-fed rats was 30-50% less efficient than
      S9 from pair-fed rats in activating arylamines (2-aminofluorene, 2
      aminoanthracene and 2-acetylaminofluorene) to mutagens in Salmonella typhimurium
      TA98 and TA100. Cytosolic fractions from ethanol-fed animals always resulted in
      greater arylamine activation than that of controls whereas the opposite was true
      of the microsomal compartment in which the ethanol-treated group was consistently
      less active than the controls. The cytosolic N-acetyltransferase activities with
      respect to 2 different substrates, isoniazid and 2-aminofluorene, were unaffected
      by ethanol consumption, indicating that this activity probably does not account
      for the different activation profiles exhibited by the ethanol and pair-fed
      cytosolic systems. Both the cytosolic and microsomal compartments are required
      for maximal expression of the mutagenicity of each arylamine however, each
      compartment can activate arylamines independently of the other. Reconstituting
      cytosol with microsomes from ethanol- and pair-fed rats, but not Aroclor
      pretreated rats, resulted in a synergistic activation of the aromatic amines and
      displayed an effect similar to that of S9. Compared to Aroclor pretreatment and
      pair-fed controls, microsomes from ethanol-fed rats displayed the least capacity
      for activating any of the arylamines to mutagens. Microsomes from Aroclor
      pretreated rats accounted for at least 80% of the S9-mediated activation of each
      of the arylamines to mutagenic metabolites which was in marked contrast to the
      contribution of the microsomal fractions to the S9 activity in the ethanol- (5
      20% of S9 activity) and pair-fed systems (22-30% of S9 activity). The data
      indicate that 2 opposing reactions occur in S9, a cytosolic activity that
      augments and a microsomal activity that attenuates the mutagenicity of
      arylamines. Both activities are modified by ethanol consumption and Aroclor
      pretreatment.

PMID- 2002801
TI  - Effect of thiols on micronucleus frequency in gamma-irradiated mammalian cells.
AB  - The effects of the thiols cysteamine, WR-1065, and WR-255591 on radiation-induced
      micronucleus (MN) frequency and cell killing were compared in cultured Chinese
      hamster ovary cells. MN were measured using the cytochalasin B assay of Fenech
      and Morley (1985), which minimizes the effect of cytokinetic perturbations on MN
      expression. The dose-response curves for MN induction were curvilinear both for
      control cells at doses between 1.5 and 4.5 Gy and for thiol-treated cells at
      doses between 3 and 9 Gy. Protection against MN induction by each thiol was
      independent of radiation dose. Furthermore, there was a close correlation between
      the degree of modification of MN induction and cell survival by each thiol, i.e.,
      the MN frequency closely predicted the survival level regardless of the presence
      of absence of the thiols. A similar predictive relationship has also been
      reported by us for cell survival and DNA double-strand break (DSB) induction in
      this cell line following treatment with these same thiols. Collectively, these
      data support the hypothesis that, for DNA-repair-proficient mammalian cells
      treated with radiomodifying agents that do not alter DNA-repair processes, MN and
      DSB induction are predictive of the level of radiation lethality and of each
      other.

PMID- 2002802
TI  - Micronuclei and chromosome aberrations in Xenopus laevis spermatocytes and
      spermatids exposed to adriamycin and colcemid.
AB  - Cultured testes and spermatocytes from the frog Xenopus laevis have been
      incubated (40-42 h) with adriamycin or colcemid followed by quantitation of
      chromosome aberrations in secondary spermatocytes and quantitation of micronuclei
      in secondary spermatocytes, early round spermatids, and round spermatids with
      acrosomal vacuoles (AV) at 18-162 h of culture. Micronucleus frequencies were
      consistently higher in secondary spermatocytes relative to round spermatids after
      exposure to either adriamycin or colcemid due to a higher rate of micronucleus
      formation during meiosis I compared to meiosis II. Also, some of the micronuclei
      formed during meiosis I did not survive meiosis II to form micronucleated
      spermatids. Micronucleus formation occurred in 3-7% of secondary spermatocytes
      with detectable chromosome aberrations, depending upon drug treatment. Thus, the
      ratio of micronuclei to total chromosome aberrations in secondary spermatocytes
      was always higher in colcemid-treated cells compared to adriamycin-treated cells
      following 18- and 42-h treatment periods. Adriamycin induced significant
      increases in micronuclei in both secondary spermatocytes and spermatids after 162
      h of culture, the time for initial pachytene stages to develop into secondary
      spermatocytes and spermatids. The data show that cultured testes and
      spermatocytes from Xenopus may be used to quantify specific meiotic chromosome
      aberrations induced by both clastogens and spindle poisons using either a rapid
      secondary spermatocyte micronucleus assay or meiotic chromosome analysis.

PMID- 2002803
TI  - Pro-oxidative interactions of dithranol with human phagocytes promote oxidative
      damage to DNA of bystander leucocytes.
AB  - Dithranol at therapeutic concentrations (5-40 micrograms ml-1) induced strand
      breaks in human leucocyte DNA in vitro in a dose-related manner. Leucocytes from
      individuals with chronic granulomatous disease (CGD) incurred substantially less
      DNA strand breaks than did normal leucocytes during exposure to dithranol
      indicating that activated phagocytes are involved. H-7, 4-beta-bromophenacyl
      bromide (BPB) and staurosporine, all inhibitors of protein kinase C, decreased
      both dithranol-mediated activation of the phagocyte respiratory burst and
      induction of DNA strand breaks. Similar effects were observed with the hydrogen
      peroxide scavenger catalase. These results suggest that dithranol induces DNA
      strand breaks, mainly as a result of pro-oxidative interactions with phagocytes.

PMID- 2002804
TI  - DNA sequence analysis of spontaneous and beta-methoxy-acrolein-induced mutations
      in Salmonella typhimurium hisD3052.
AB  - The histidine auxotroph hisD3052 results from a single base-pair deletion (C:G)
      from the 298th codon (alanine) in the D gene of the histidine operon of S.
      typhimurium LT-2. Bacteria carrying this mutation revert to histidine prototrophy
      by frameshift mutations (additions or deletions) that restore the correct reading
      frame. Among the compounds that revert hisD3052 are the naturally occurring
      dicarbonyl compound malondialdehyde and a structural analog, beta-methoxy
      acrolein. To determine the sequence changes responsible for reversion,
      spontaneous and beta-methoxy-acrolein induced revertants were isolated, male
      derivatives constructed, and infected with M13Ho167.18, a phage carrying partial
      O, D, and C genes of the histidine operon. M13hisD+ recombinants were selected by
      complementation in TA2890, single-stranded DNA was isolated, and the reverted D
      genes were sequenced using Sanger dideoxy chain-termination sequencing with a
      synthetic oligonucleotide primer. Analysis of 37 spontaneous revertants revealed
      41% additions and 59% deletions with 22% of the mutations occurring as two base
      pair (-CG-) deletions in a -CG- rich 'hot spot'. The profile of additions was +1
      (30%), +4 (8%), +7 (3%); the profile of deletions was -2 (32%), -5 (11%), -8
      (8%), and -11 (8%). Analysis of 27 beta-methoxy-acrolein-induced revertants
      revealed 96% additions and 4% deletions. The profile of induced additions was +1
      (70%), +4 (22%), +7 (4%). No additions occurred in the -CG- rich hot-spot.
      Frameshift reversions of the hisD3052 gene demonstrate a surprising degree of
      sequence diversity and reveal the ability of the hisD3052 tester strain to detect
      a wide variety of frameshift reversion events. In addition, the results
      demonstrate that beta-methoxy-acrolein induces a high percentage of additions in
      this reversion system.

PMID- 2002805
TI  - In vitro mutagenesis in the lacI gene of Escherichia coli: fate of 3'-terminal
      mispairs versus internal base mispairs in a transfection assay.
AB  - The fate of G.T mismatches and frameshifts, present at the 3'-terminus of primer
      template or internally, has been studied with a combined transfection and
      electrophoretic assay following in vitro polymerization by DNA polymerase I
      (Klenow enzyme) of Escherichia coli. Several synthetic oligodeoxynucleotide
      primers were synthesized and annealed to uracil-containing single-stranded DNA of
      M13 phage bearing the lacI gene, to produce 1-3 consecutive G.T mismatches in the
      middle of the duplex region or at the 3'-OH end of the primer. Additional
      mismatched primer-templates were prepared, in which the primer had a deleted
      nucleotide, an extra nucleotide or both G.T mismatch and an extra nucleotide. The
      extension or degradation of these primers during in vitro DNA synthesis in the
      presence of all 4 dNTPs ('complete' reaction) or in the absence of dATP ('-A'
      reaction) was monitored by gel electrophoresis. Duplex DNA products were used in
      a transfection assay and the nucleotide changes in i-mutant progeny were
      determined by sequence analysis. The results suggest that whereas a single 3'
      terminal G.T mismatch is relatively stable in chain elongation by Klenow enzyme,
      multiple terminal G.T mismatches are degraded by the 3'-exonuclease activity of
      this polymerase prior to primer extension. This editing activity is increased
      with the number of 3'-terminal mispairs. Single, double and triple T----C base
      substitutions were efficiently recovered when the mismatches occurred internally.
      Also, single-base eliminations or additions were readily recovered when the
      mutagenic primers contained an internal base deletion or addition, respectively.
      When products of the '-A' misincorporation reaction (catalyzed by Klenow enzyme)
      were assayed by transfection, base substitutions (exclusively T----C), but no
      frameshifts, were recovered. The results indicate that the absence of multiple
      tandem base substitutions among i- mutants recovered following primer elongation
      under mutagenic 'minus' conditions was due to the efficient action of the 3'
      exonuclease activity of the Klenow enzyme on multiple terminal mismatches during
      in vitro polymerization, rather than to in vivo events (lack of expression or
      occurrence of mismatch repair) in the M13-lacI transfection assay.

PMID- 2002806
TI  - Induction of rat liver DNA alterations by chronic administration of peroxisome
      proliferators as detected by 32P-postlabeling.
AB  - The mechanisms of the hepatocarcinogenicity of non-mutagenic peroxisome
      proliferators, i.e. compounds used as hypolipidemic drugs and industrial
      plasticizers, are not sufficiently understood. To gain more information on the
      mechanism of their action, the chronic effects of two structurally diverse
      peroxisome proliferators on rat-liver DNA were investigated by the 32P
      postlabeling assay. Male F-344 rats (1.5 month old) were fed ciprofibrate
      (0.025%) in the diet for 2, 5, 8, and 16 months or Wy-14643 (0.1%) for 18 months.
      Liver DNA from individual treated animals (3-4 per group) and age-matched
      controls was analyzed by the nuclease P1/bisphosphate version of the 32P
      postlabeling assay. Three distinct types of exposure-related DNA alterations were
      observed: (i) A significant reduction of the age-dependent accumulation of I
      compounds (putative indigenous DNA modifications) (type 1), (ii) adduct-like DNA
      derivatives induced by the treatments (type 2), and (iii) as yet structurally
      uncharacterized radiolabeled material occupying substantial areas of DNA adduct
      maps and accumulating in an exposure time-dependent manner (type 3). DNA from
      liver tumors generated by these agents displayed only traces of I-compounds,
      lacked all but one adduct-like derivatives, and had no type 3 alterations. Thus,
      in contrast to the non-mutagenicity of peroxisome proliferators in short-term
      assays, chronic administration of these compounds led to DNA alterations that
      were detectable by 32P-postlabeling assay.

PMID- 2002807
TI  - Evaluation of the DNA-repair host-mediated assay. III. Relationship between
      metabolic activation of dimethylnitrosamine and organ-specific differential
      lethality induced in E. coli indicator strains.
AB  - In the present study the sensitivity of differential lethality as an endpoint for
      monitoring the presence of organ-specific genotoxic factors within the DNA-repair
      host-mediated assay (HMA) was determined. The induction of differential lethality
      in chemically exposed animals was assessed by measuring the recovery ratio Q,
      i.e., the relative survival of a repair-deficient E. coli K-12 derivative in
      comparison with its repair-proficient counterpart. Using untreated animals the
      interindividual fluctuation of the recovery ratio Q was first quantified and then
      used to determine the level below which it could be considered indicative of
      chemically induced differential lethality. This Q value was found to be 0.65 or
      lower. Using this criterion, a significant decrease of the Q value was observed
      in mice exposed to DMNA at a dose level as low as 15-30 mumole/kg, i.p. Inter
      organ transport (liver----extrahepatic organs) of indicator bacteria was studied
      in reconstruction experiments using the direct-acting methylating agent MNU.
      These studies showed that inter-organ transport of indicator bacteria did not
      interfere with MNU-induced differential lethality. Time-related experiments were
      used to study the effects of inter-organ transport of genotoxic DMNA metabolites.
      In these studies significant, time-related differences were found in the
      induction of differential lethality in various organs of mice treated with DMNA.
      At a dose level of 200 mumole/kg (i.p.) genotoxic factors appeared within 25 min
      after administration in the liver. In the lungs and kidneys such factors appeared
      at a substantially slower rate, e.g., 20-120 min after DMNA administration. In
      persistence experiments differential lethality reached a maximum 30 min after
      DMNA treatment. No residual effects were detected 60 min after the injection of
      the carcinogen. These experiments showed that DMNA-derived genotoxic factors
      diffused from the liver into the bloodstream. The diffusion of these reactive
      species followed by their transport via the bloodstream to the lungs accounted
      for maximally 50% of differential lethality observed in bacteria recovered from
      the latter organ. In contrast, no indications were found for the transport of
      genotoxic DMNA metabolites from the liver via the bloodstream to the spleen and
      the kidneys. These results show that organ-specific effects observed in the DNA
      repair HMA procedure after DMNA exposure can be primarily attributed to in situ
      metabolism, rather than diffusion of genotoxic metabolites from the liver to
      extrahepatic organs.

PMID- 2002808
TI  - About the mutagenicity of chlorine-substituted furanones and halopropenals. A
      QSAR study using molecular orbital indices.
AB  - Electron affinities, frontier molecular orbital energies and electron densities
      at individual carbon atoms were calculated for 11 chlorofuranones including the
      strong mutagen 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) and for
      5 halopropenals by semi-empirical AM1 and ab initio STO-3G methods. Significant
      correlations were found between Ames TA100 mutagenicity and the following AM1
      electronic parameters of chlorofuranones: electron affinity (r = 0.9556). LUMO
      energy (r = 0.9332) and frontier electron density of LUMO at the alpha-carbon (r
      = 0.8882). In halopropenals only LUMO electron density at the beta-carbon
      correlates well with mutagenicity. The observed correlations suggest a reaction
      mechanism in which chlorofuranones and halopropenals act as electron acceptors in
      the interaction with DNA.

PMID- 2002809
TI  - Genetic analysis of ionising radiation sensitive mutants of cultured mammalian
      cell lines.
AB  - The genetic diversity of a range of ionising radiation sensitive mutants of
      cultured mammalian cell lines has been examined. Hybrids were constructed from
      suitably marked diploid cells by cell fusion and selected using resistance to HAT
      and ouabain. Hybrids were examined for ploidy and gamma-ray sensitivity. The data
      suggest that at least 8 and possibly 9 complementation groups exist which confer
      sensitivity to ionising radiation. Mutants in at least 3 distinct complementation
      groups have a reduced ability to rejoin DNA double-strand breaks.

PMID- 2002810
TI  - The genetic basis of resistance to ionising radiation damage in cultured
      mammalian cells.
AB  - To test the genetic similarity of independently-isolated hamster cell mutants
      sensitive to ionising radiation, these were fused in pairs and the hybrids
      exposed to X-rays. Some mutants (irs1, irs3, xrs-1, XR-1, BLM2) were found to
      complement all others tested for radiosensitivity in hybrids, and are therefore
      in separate genetic groups. The mutants irs2 and V-E5, both isolated from V79
      cells, did not complement and therefore belong to the same group. Another pair,
      EM7 and irs1SF, formed hybrids with intermediate levels of survival between
      mutant and wild-type. However, the parental cells fused to irs1SF also showed
      intermediate sensitivity, suggesting a semi-dominant mutant phenotype rather than
      a lack of complementation. Crosses of some of these hamster mutants to the
      radiosensitive mouse mutant M10 showed clear complementation (irs1 x M10, irs2 x
      M10) but for others the complementation did not greatly exceed the sensitivity of
      one (irs3 x M10) or both mutants (XR-1 x M10). Taken with our previously
      published data, these results show that there are at least 8 genetic groups
      determining resistance to ionising radiation damage in rodent cells.

PMID- 2002811
TI  - Effect of passaging on Mer phenotype of human fetal cell cultures.
AB  - With increasing passage in culture, the human fibroblast cell strain GM11 lost
      the Mer+ phenotype (the ability to support the growth of adenovirus 5 damaged
      prior to infection by MNNG). All of 46 embryonic strains prepared either from
      various organs of 20 fetuses from 6-7 to 13-14 weeks of gestational age or from
      two hydatidiform moles showed normal repair of MNNG-treated virus. We conclude
      that human fetal strains are not usually deficient in such repair, and that the
      behavior of GM11 is atypical.

PMID- 2002812
TI  - Establishment of a monoclonal antibody recognizing cyclobutane-type thymine
      dimers in DNA: a comparative study with 64M-1 antibody specific for (6
      4)photoproducts.
AB  - We obtained a monoclonal antibody (TDM-1) binding to 313-nm UV-irradiated DNA in
      the presence of acetophenone. The binding of TDM-1 to 254-nm UV-irradiated DNA
      was not reduced with the subsequent irradiation of 313-nm UV. Furthermore, the
      treatment of UV-irradiated DNA with photolyase from E. coli and visible light
      exposure reduced both the antibody binding and the amount of thymine dimers in
      the DNA. A competitive inhibition assay revealed that the binding of TDM-1 to UV
      irradiated DNA was inhibited with photolyase, but not with 64M-1 antibody
      specific for (6-4)photoproducts. These results suggest that TDM-1 antibody
      recognizes cyclobutane-type thymine dimers in DNA. Using TDM-1 and 64M-1
      antibodies, we differentially measured each type of damage in DNA extracted from
      UV-irradiated mammalian cells. Repair experiments confirm that thymine dimers are
      excised from UV-irradiated cellular DNA more slowly than (6-4)photoproducts, and
      that the excision rates of thymine dimers and (6-4)photoproducts are lower in
      mouse NIH3T3 cells than in human cells.

PMID- 2002813
TI  - Dose-dependent increase in repair of 1-beta-D-arabinofuranosylcytosine-detectable
      DNA lesions in UV-treated xeroderma pigmentosum (group A) fibroblasts.
AB  - The extent of DNA-excision repair was determined in human fibroblast strains from
      clinically normal and xeroderma pigmentosum complementation group A (XP-A) donors
      after irradiation with 254-nm ultraviolet (UV) light. Repair was monitored by the
      use of 1-beta-D-arabinofuranosylcytosine (araC), a potent inhibitor of DNA
      synthesis, and alkaline sucrose velocity sedimentation to quantitate DNA single
      strand breaks. In this approach, the number of araC-accumulated breaks in post-UV
      incubated cultures becomes a measure of the efficiency of a particular strain to
      perform long-patch excision repair. The maximal rate of removal of araC
      detectable DNA lesions equalled approximately 1.8 sites/10(8) dalton/h in the
      normal strains (GM38, GM43), while it was more than 10-fold lower in both XP-A
      strains (XP4LO, XP12BE) examined. In normal fibroblasts the number of lesions
      removed during the first 4 h after irradiation saturated at approximately 10
      J/m2. In contrast, the residual amount of repair in the excision-deficient cells
      increased as a linear function of UV fluence over a range 5-120 J/m2. Thus we
      conclude that the repair of araC-detectable UV photoproducts in XP group A
      fibroblasts is limited by availability of damaged regions in the genome to repair
      complexes.

PMID- 2002814
TI  - Role of bacterial nitroreductase and O-acetyltransferase in urine mutagenicity
      assay of rats exposed to 2,4,6-trinitrotoluene (TNT).
AB  - The urine mutagenicity of rats exposed to 2,4,6-trinitrotoluene (TNT) by i.p.
      injection was studied in the Salmonella assay using indicator strains with
      various levels of 'classical' nitroreductase or acetyl-CoA:N-hydroxylarylamine O
      acetyltransferase activity. The strains used were the conventional Salmonella
      typhimurium TA98, nitroreductase-deficient TA98NR and -overproducing YG1021, and
      O-acetyltransferase-deficient TA98/1,8-DNP6 and -overproducing YG1024. TA98,
      YG1021 and YG1024 clearly detected the increase of direct urine mutagenicity. A
      slight increase of mutagenicity was also detected with metabolic activation in
      YG1021 and YG1024. High levels of both nitroreductase and O-acetyltransferase
      significantly increased the sensitivity of the indicator strain to the
      mutagenicity of urine caused by TNT exposure, while the nitroreductase- or O
      acetyltransferase-deficient strains gave negative responses.

PMID- 2002815
TI  - Investigation of soy sauce treated with nitrite in the chromosomal aberration
      test in vitro and the micronucleus test in vivo.
AB  - Soy sauce pretreated with 2300 ppm nitrite caused no more aberrations than did
      untreated soy sauce in the chromosomal aberration test in vitro using a Chinese
      hamster fibroblast cell line with or without S9 mixture. The aberration induction
      by soy sauce is likely to be caused by the 17% sodium chloride it contains. Soy
      sauce with or without pretreatment with 2300 ppm nitrite was orally given to ICR
      mice at a dose of 14 ml/kg body weight once or 6 ml/kg body weight/day for 5
      consecutive days. This oral administration did not induce any significant
      increase in micronuclei in the micronucleus test in vivo.

PMID- 2002816
TI  - Identification and cloning of a umu locus in Streptomyces coelicolor A3(2).
AB  - The umuDC operon of Escherichia coli is required for efficient mutagenesis by UV
      and many other DNA-damaging agents. E. coli umu mutants are defective in
      mutagenesis and slightly more sensitive to DNA-damaging agents. The existence of
      a umuDC analogue in Streptomyces coelicolor was suggested by data of our previous
      works. We cloned from Streptomyces coelicolor a fragment of DNA homologous to the
      E. coli umuDC region that is able to complement the E coli umuC122::Tn5 mutation.
      Therefore our data suggest that S. coelicolor contains a functional umu-like
      operon.

PMID- 2002817
TI  - The effect on lymphocyte chromosomes of additional radiation burden due to
      fallout in Salzburg (Austria) from the Chernobyl accident.
AB  - An investigation has been carried out to determine whether chromosome aberrations
      in peripheral blood lymphocytes reflect the elevated environmental dose of low
      LET ionising radiation, mainly due to radiocesium from Chernobyl fallout, to the
      population living in Salzburg city. Sixteen volunteers were sampled 1 year after
      the Chernobyl accident. Two of these persons were also sampled before the
      accident, and then in 1988 and 1990. The radioactive environment of Salzburg city
      and the radiation burden of its inhabitants have been frequently determined
      before and after the accident. The Cs-137 content of the volunteers was measured
      by whole-body counting. The additional external plus internal radiation doses in
      the year 1987 to the tested individuals ranged between 15 and 68% of the former
      normal environmental burden. The aberration frequencies showed a sharp increase
      of about a factor 6 from the pre-Chernobyl dose rate (0.9. mGy/year) to the post
      Chernobyl dose rate (about 2 mGy/year total) but then decreased again with higher
      additional dose. In the two persons analysed before and up to 4 years after the
      accident the aberration yield showed a significant increase from 1984/85 to 1987,
      a decrease in 1988 and a further decrease in 1990. If these last 2 values are
      plotted against additional dose they fit the curve of the pooled 1987 values. The
      dose-effect curves revealed the same tendency as we found in various previous
      investigations and support the assumption that repair enzymes could be triggered
      by a certain amount of damage to the DNA.

PMID- 2002818
TI  - Trends in serum cholesterol levels from 1980 to 1987. The Minnesota Heart Survey.
AB  - BACKGROUND AND METHODS: We assessed community trends in the awareness, treatment,
      and control of hypercholesterolemia (defined as a serum cholesterol level greater
      than 6.21 mmol per liter [240 mg per deciliter]) during the 1980s in the
      Minneapolis-St. Paul (Twin Cities) metropolitan area. Twin Cities residents 25 to
      74 years old participated in independent, cross-sectional, population-based
      surveys of risk factors for cardiovascular disease in 1980-1982 (n = 3365) and
      1985-1987 (n = 4545). RESULTS: Mean serum total cholesterol levels, as adjusted
      for age, decreased significantly (P less than 0.01) from 1980-1982 to 1985-1987
      in men (from 5.30 mmol per liter [205 mg per deciliter] to 5.16 mmol per liter
      [200 mg per deciliter]) and women (from 5.19 mmol per liter [201 mg per
      deciliter] to 5.04 mmol per liter [195 mg per deciliter]). The prevalence of
      hypercholesterolemia as adjusted for age decreased significantly (P less than
      0.05) in men (17.8 to 15.1 percent) and women (17.1 to 13.6 percent). The ratio
      of total cholesterol to high-density lipoprotein (HDL) cholesterol was unchanged
      during this period, because of a concurrent decline in the level of HDL
      cholesterol. Participants with hypercholesterolemia in the 1985-1987 survey were
      more likely than those in the 1980-1982 survey to be aware of their condition
      (32.6 vs. 25.4 percent), to be treated with lipid-lowering agents (4.3 vs. 1.9
      percent), and to have their condition controlled (1.9 vs. 0.3 percent). Among
      those who reported treatment by a physician for hyperlipidemia, changes were
      observed in the type of treatment recommended. A significant increase (P less
      than 0.05) was noted from 1980-1982 to 1985-1987 in the percentage of men being
      treated for hyperlipidemia with lipid-lowering medication (5.2 vs. 11.6 percent)
      and with exercise programs (10.3 vs. 20.1 percent). In women being treated for
      hyperlipidemia, a nonsignificant increase was noted in the use of lipid-lowering
      medication (8.2 vs. 13.9 percent), and a significant increase (P less than 0.05)
      was observed in the number of exercise prescriptions (4.1 vs. 12.0 percent).
      CONCLUSIONS: We found a substantial decline in the prevalence of
      hypercholesterolemia in the Twin Cities between 1980-1982 and 1985-1987 that may
      be attributed to changes in lifestyle, such as diet and exercise, and to a lesser
      extent to more aggressive intervention with lipid-lowering drugs by physicians.

PMID- 2002819
TI  - Omeprazole.

PMID- 2002820
TI  - Allergic reactions to milk-contaminated "nondairy" products.

PMID- 2002821
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 14-1991. A 17-week-old boy with a left posterior intrathoracic
      mass.

PMID- 2002822
TI  - Hepatic fibrosis--new therapeutic approaches.

PMID- 2002823
TI  - Treatments for Graves' disease--letting the thyroid rest.

PMID- 2002824
TI  - Coffee, caffeine, and cardiovascular disease.

PMID- 2002825
TI  - Treatment of hypertensive crisis.

PMID- 2002826
TI  - Single-use syringes.

PMID- 2002827
TI  - Handedness and life span.

PMID- 2002828
TI  - Scientific and commercial development of human cell lines. Issues of property,
      ethics, and conflict of interest.

PMID- 2002829
TI  - A report on forged teams and enforced chaos. 6th Daisy Ayris memorial lecture,
      NATN Congress 1990.

PMID- 2002830
TI  - To clamp or not to clamp? A look at the way doctors and nurses deal with
      underwater seal chest drainage.

PMID- 2002831
TI  - A common problem. A study of a patient undergoing trans-urethral resection of
      bladder tumour.

PMID- 2002832
TI  - The care and treatment of the multi-traumatised patient--Part I.

PMID- 2002833
TI  - Apart from that...

PMID- 2002834
TI  - Duesberg on AIDS and HIV.

PMID- 2002835
TI  - Radiation doses.

PMID- 2002836
TI  - A dose of vitamins and a pinch of salt.

PMID- 2002837
TI  - Turning on and turning off the sense of smell.

PMID- 2002838
TI  - Circadian rhythms. Resetting the human clock.

PMID- 2002839
TI  - Radical copper in oxidases.

PMID- 2002840
TI  - Evolutionary ecology. How to live like a mammal.

PMID- 2002841
TI  - Radiation doses and cancer.

PMID- 2002842
TI  - Fetal clues to handedness.

PMID- 2002843
TI  - BSE. First vache folle.

PMID- 2002844
TI  - IQ data controversy.

PMID- 2002845
TI  - Light-induced suppression of endogenous circadian amplitude in humans.
AB  - Winfree reported 20 years ago the intriguing finding that a light stimulus of a
      critical strength applied at a critical circadian phase could essentially stop
      the circadian clock in Drosophila pseudo-obscura by resetting the circadian
      oscillator close to its singularity (a phaseless position at which the amplitude
      of circadian oscillation is zero). Since then, similar observations of attenuated
      circadian amplitude in response to critical stimuli have been limited to
      unicells, insects and plants. Our recent demonstration that the phase of the
      human circadian pacemaker could be inverted using an unconventional three-cycle
      stimulus led us to investigate whether critically timed exposure to a more
      moderate stimulus could drive that oscillator towards its singularity. Here we
      report that exposure of humans to fewer cycles of bright light, centred around
      the time at which the human circadian pacemaker is most sensitive to light
      induced phase shifts, can markedly attenuate endogenous circadian amplitude. In
      some cases this results in an apparent loss of rhythmicity, as expected to occur
      in the region of singularity.

PMID- 2002846
TI  - Cetus retains PCR patents.

PMID- 2002848
TI  - World's first MS unit.

PMID- 2002847
TI  - A discrete sequence in a platelet integrin is involved in ligand recognition.
AB  - Platelet membrane glycoprotein IIb-IIIa (gpIIb-IIIa; alpha IIb-beta 3), the most
      prominent member of the integrin family of adhesion receptors on these cells,
      mediates platelet aggregation by binding fibrinogen and is critical in thrombosis
      and haemostasis. A short amino-acid sequence at the carboxy terminus of the gamma
      chain of fibrinogen is recognized by gpIIb-IIIa and peptides containing this
      sequence are selectively crosslinked to residues 294-314 of gpIIb. Here we show
      that an 11-residue peptide from this region of gpIIb inhibits platelet
      aggregation and binding of fibrinogen to platelets and to purified gpIIb-IIIa,
      and that it interacts directly with fibrinogen. These results implicate this
      segment of gpIIb-IIIa in the ligand-binding function of the receptor. Moreover,
      as this region is highly conserved among integrins, it may have a general
      function in ligand recognition by this broadly distributed family of adhesion
      receptors.

PMID- 2002849
TI  - Conversion by retinoic acid of anterior cells into ZPA cells in the chick wing
      bud.
AB  - In recent years there has been considerable interest in the role of retinoic acid
      (RA) in vertebrate-limb pattern formation. When RA is applied to the anterior of
      the chick wing bud, a mirror-image duplication of the limb pattern develops that
      is identical to the pattern resulting from grafts of posterior tissue (zone of
      polarizing activity, or ZPA). It has been proposed that position along the
      anterior-posterior axis in the chick limb is specified by a gradient of a
      diffusible factor produced by the ZPA. The ZPA-mimicking action of RA has led to
      the hypothesis that exogenously applied RA acts by providing graded spatial
      information across the anterior-posterior limb axis. An alternative
      interpretation is that RA changes anterior cells into ZPA cells, which in turn
      provide the actual pattern-duplicating stimulus; there is already some
      preliminary evidence that this occurs. A hybrid interpretation has also been
      suggested whereby ZPA cells are formed in response to RA exposure and then begin
      to release retinoids that act as graded spatial cues. We have used a functional
      assay to test anterior chick wing-bud cells for ZPA activity after exposure to
      RA. The results of our studies indicate that the action of RA is to change
      anterior cells into ZPA cells. Further, our results indicate that it is unlikely
      that RA-treated anterior cells then begin producing RA in such a way as to
      provide a graded positional signal.

PMID- 2002850
TI  - Novel thioether bond revealed by a 1.7 A crystal structure of galactose oxidase.
AB  - Galactose oxidase is an extracellular enzyme secreted by the fungus Dactylium
      dendroides. It is monomeric, with a relative molecular mass of 68,000, catalyses
      the stereospecific oxidation of a broad range of primary alcohol substrates and
      possesses a unique mononuclear copper site essential for catalysing a two
      electron transfer reaction during the oxidation of primary alcohols to
      corresponding aldehydes. Recent evidence arguing against a Cu(III)-Cu(I) couple
      implies the existence of a second redox-active site proposed to involve
      pyrroloquinoline quinone or a tyrosine radical. We now report the crystal
      structure of galactose oxidase at 1.7 A resolution. This reveals a unique
      structural feature at the copper site with a novel thioether bond linking Cys 228
      and Tyr 272 in a stacking interaction with Trp 290. We propose that these
      molecular components stabilize the protein free-radical species essential for
      catalysis and thus provide a 'built-in' secondary cofactor. This feature may
      represent a new mechanism for mediating electron transfer in metalloenzymes in
      the absence of exogenous cofactors.

PMID- 2002851
TI  - So what's new?

PMID- 2002852
TI  - [Carbon monoxide poisoning].

PMID- 2002853
TI  - [Pathophysiological basis of the adult respiratory distress syndrome: the role of
      leukocytes and oxygen radicals].

PMID- 2002854
TI  - [Clinical aspects of the so-called adult respiratory distress syndrome].

PMID- 2002855
TI  - [The diagnostic value of immunoscintigraphy using the monoclonal antibody OV-TL3
      in patients with ovarian carcinoma].
AB  - Immunoscintigraphy, using radiolabeled monoclonal antibodies directed against
      tumor associated antigens, is a relatively new method for the detection of tumour
      localizations. The diagnostic accuracy of immunoscintigraphy was compared with
      computer tomography, magnetic resonance imaging, ultrasound, physical
      examination, and the CA 125 serum assay in patients suspected of having primary
      or recurrent ovarian cancer. One mg of the murine monoclonal antibody OV-TL3
      F(ab')2 was labeled with 4 mCi 111Indium and administered intravenously to 28
      patients. No adverse reactions were noted. Twenty patients underwent extensive
      explorative laparotomy 3 to 8 (median 4 days) days after injection of the
      immunoconjugate, allowing a histopathological verification of the actual tumour
      status of each patient. The sensitivity of immunoscintigraphy for the detection
      of ovarian cancer was at least equal to that of the other diagnostic methods.
      However, with immunoscintigraphy more tumour localizations were identified.

PMID- 2002856
TI  - [Zidovudine treatment and need of blood transfusion in patients with AIDS].
AB  - The treatment of AIDS patients with zidovudine extends their survival time.
      However, hematological side effects frequently require a reduction of the dosage
      and the administration of blood transfusions. We reviewed the history of
      zidovudine treatment and blood transfusions for 27 patients with AIDS treated in
      the University Hospital Utrecht between July 1st, 1987 and July 1st, 1990. The
      initial dosage of zidovudine was 1000-1200 mg daily orally. Two months after the
      initiation of the therapy, 48% of the patients required a reduction of the
      zidovudine dosage. This percentage had increased to 85% after 12 months since the
      start of the therapy. During this period, 26% of the patients received blood
      transfusions. The zidovudine dosage was on the average of 480 mg per day after
      reduction. One year after the start of the therapy, 81% of the patients were
      still alive, and after 1 1/2 years this percentage was 68. In our study the
      proportion of patients undergoing a reduction of the zidovudine dosage was high
      in comparison with data reported in the literature. However, the need for blood
      transfusions was clearly lower. The survival percentages after 1 and 1 1/2 years
      were about the same as reported in other studies. Therefore, we conclude that an
      early reduction of the zidovudine dosage and resulting low total dosage were
      effective and resulted in a decreased need for blood transfusions.

PMID- 2002857
TI  - [Pasteurella multocida infections: bites by dogs or cats?].
AB  - Annually 50,000 to 100,000 animal bites are seen by physicians in the
      Netherlands. Infections of these bite wounds frequently occur. Pasteurella
      multocida is one of the main causes of these infections and many serious
      complications may occur. We present 3 patients with disturbances in wound healing
      after animal bites or scratches due to infection with P. multocida. In view of
      the high infection ratio after cat bites we advise giving amoxicillin/clavulanic
      acid (Augmentin) for 5 days as prophylaxis. According to the literature
      prophylaxis for dog bites is not necessary. However, fatal complications after
      dog bites due to infections with Capnocytophaga canimorsus (DF-2) support those
      who prefer to give antibiotics after these bites also.

PMID- 2002858
TI  - [Standards of care and consensus; various legal aspects].

PMID- 2002859
TI  - [How many home deliveries are needed to maintain proficiency?].

PMID- 2002860
TI  - [Farmacotherapeutisch Kompas 1990-1991].

PMID- 2002861
TI  - [Transcultural surgical obstetrics].

PMID- 2002862
TI  - [Eurothemes. The Netherlands through the eyes of a Polish surgeon].

PMID- 2002863
TI  - [The use of erythropoietin].

PMID- 2002864
TI  - [An end to office hours for warts? A randomized study of the effectiveness of
      liquid nitrogen and of the Histofreezer].
AB  - OBJECTIVE: Comparison of the effectiveness of liquid nitrogen and of cryotherapy
      by means of the Histofreezer in the treatment of hand warts. DESIGN: Randomized
      therapeutic trial. SETTING: Six general practices in Limburg, The Netherlands.
      PATIENTS AND METHODS: Of the patients 43 (with 83 warts) were treated with
      nitrogen (if necessary twice) and 50 (with 108 warts) with the Histofreezer (if
      necessary 4 times), with a final control visit after 2.5 months. After a training
      session, the general practitioners performed the treatments and the observations.
      In these groups, 7 patients (with 18 warts) and 10 patients (with 20 warts)
      respectively did not fully comply with the protocol. At the start the number of
      warts per patient, their size, protruberance and localization were registered.
      Statistical analysis was performed by chi 2 test (unpaired case) in an intention
      to treat approach and of compliers only. OUTCOME MEASURES: Disappearance of
      warts, pain (on a 3-point scale), wounds, depigmentation. Non-compliers were
      asked by telephone if their warts had been cured. RESULTS: Of all patients 58%
      was cured by liquid nitrogen and 28% by Histofreezer (p = 0.01). Among the
      compliers these percentages were 67% and 35% of the patients (p = 0.01) and 66%
      and 49% of the warts (p = 0.08). The treatments were about equally effective in
      dorsal non protuberant and small (less than 5 mm) warts, and among young (less
      than 20 years) patients. CONCLUSION: The overall results of liquid nitrogen were
      better. The Histofreezer seems to be attractive in certain cases (e.g. children),
      but this should be the subject of further study.

PMID- 2002865
TI  - [The forearm: no longer a suitable area for obtaining grafts for skin defects of
      the hand].
AB  - In the emergency room, as well as during elective surgery, the surgeon is often
      confronted with an absolute skin defect. In the older books on hand surgery the
      inner, volar aspect of the forearm was advised as a suitable donor area for skin
      grafts of either split or full thickness. Nowadays, the disfigurement in the
      donor area is considered unjustifiable. Since it is almost impossible to correct
      these scars more suitable donor sites have to be looked for. Some areas are
      suggested. It is advised to avoid the forearm as a routine donor area in case of
      skin defects in the hand.

PMID- 2002866
TI  - [Was nervous consumption a precursor of anorexia nervosa?].

PMID- 2002867
TI  - [Increased mortality during the heat wave of early August 1990].

PMID- 2002868
TI  - [Privacy regulations: models of the National Council for Public Health].

PMID- 2002869
TI  - [At which preoperative hemoglobin levels is blood transfusion indicated, and does
      blood transfusion promote metastasis in malignant diseases?].

PMID- 2002870
TI  - [Invasive diagnosis and treatment of the urinary tract in the fetus].

PMID- 2002871
TI  - [Urinary incontinence in the elderly; worth a new study?].

PMID- 2002872
TI  - [Is breech presentation an indication for cesarean section?].

PMID- 2002873
TI  - [Valproic acid and stupor].

PMID- 2002874
TI  - [The effect of increased ozone levels in the outside air on lung function of
      children doing sports].

PMID- 2002875
TI  - [Carpal tunnel syndrome].

PMID- 2002876
TI  - Middle age: an evolving frontier in gerontology.

PMID- 2002877
TI  - Erythrocyte membrane characteristics indicate abnormal cellular aging in patients
      with Alzheimer's disease.
AB  - Erythrocytes from patients with Alzheimer's disease show signs of disturbance of
      the normal cellular aging process. Immunoblotting of erythrocyte membrane
      proteins from Alzheimer patients reveals increased breakdown of the anion
      transport protein band 3 in a majority of the cells, similar to what is observed
      in only a very small cell population during normal aging. These structural
      changes are accompanied by changes in anion transport characteristics, but the
      latter partially deviate from those observed during normal aging. The amount of
      erythrocyte-bound immunoglobulin G, the most direct and relevant parameter of
      erythrocyte aging, is significantly increased in Alzheimer patients relative to
      age-matched, healthy donors and to patients with multi-infarct dementia. These
      data indicate accelerated molecular breakdown of band 3 and premature appearance
      of senescent cell characteristics in erythrocytes from Alzheimer patients, and
      support the hypothesis that abnormal cellular aging may be involved in the
      etiology of the Alzheimer-specific pathology.

PMID- 2002878
TI  - Protein L-isoaspartyl methyltransferase in postmortem brains of aged humans.
AB  - The specific activity of protein L-isoaspartyl methyltransferase, an enzyme
      implicated in the metabolism of damaged, isoaspartate-containing proteins, has
      been measured in postmortem samples of parietal cortex from 30 individuals (19
      with Alzheimer's disease and 11 controls). Methyltransferase specific activity
      was positively correlated with age at death, increasing by 2.9 pmol/min/mg of
      protein for every ten years of age (r = .51, p less than 0.005). This correlation
      was significant in the control and Alzheimer's disease groups alike. Specific
      activity also appeared to be about 15% higher in females than in age- and
      diagnosis-matched males (p less than 0.05). No significant differences were
      observed between age- and sex-matched Alzheimer patients and controls, suggesting
      that a deficiency in this enzyme is not responsible for the accumulation of
      abnormal proteins in Alzheimer's disease.

PMID- 2002879
TI  - Acquisition and long-term retention of a two-lever DRL schedule: comparison
      between mature and aged rats.
AB  - The effects of ageing on temporal regulation, general activity and memory were
      analysed in a two-lever DRL schedule. The task consisted in pressing on lever A
      and then waiting a minimum of time before pressing lever B to get the reinforcer.
      Adult and senescent rats were submitted to preliminary training followed by 5 DRL
      5-second training sessions and 3 retention testing sessions after a 21-day break.
      Results showed that, relative to adults, senescent rats were slower to reach the
      5-second DRL criterion, emitted fewer temporally regulated A-B response sequences
      and an equivalent amount of repetitive superfluous A-A and B-B response
      sequences. The quality of temporal regulation was evaluated by the coefficient of
      variation (CV) and the median of the A-B interresponse-time distribution. In
      training, aged rats exhibited a higher CV only during the first 10-minute periods
      of the sessions, and emitted median IRTs similar to those of adults. The B-A
      intertrial-intervals were longer in aged than in adult rats. No age-related
      differences appeared for efficiency. Finally, long-term retention was not
      affected in either age group. The results favour an interpretation in terms of
      temporary recall memory deficit with a preservation of temporal regulation
      capacity, rather than age-related motor and motivational differences.

PMID- 2002880
TI  - Quantitation of synaptic density in the septal nuclei of young and aged Fischer
      344 rats.
AB  - Synaptic density in the medial and lateral septal nuclei was examined in 3 and 24
      28 months of age Fischer 344 rats. The lateral nucleus had a higher synaptic
      density than the medial region in both age groups. There were no statistically
      significant differences in synapse density in either region as a function of age,
      but the data suggested a subpopulation of aged animals which did show an age
      related decline in synaptic density in the lateral, but not medial area of the
      septum. These data indicate that sample size may be an important variable in
      assessing possible age-related differences in synaptic density, since a broad
      range of values, some significantly below the range of young animals, exists in
      the aged brain.

PMID- 2002881
TI  - Postnatal handling attenuates certain neuroendocrine, anatomical, and cognitive
      dysfunctions associated with aging in female rats.
AB  - Hippocampal degeneration with aging is associated with increased hypothalamic
      pituitary-adrenal (HPA) activity and, in male rats, both are attenuated by
      postnatal handling. Considering the important sex differences in the effects of
      handling and in HPA responses to stress in older rats, we have examined the
      effects of postnatal handling on aging in females. Female, Long-Evans rats were
      handled (H) during the first 3 weeks of life and later compared with nonhandled
      (NH) controls at various ages. Handling resulted in permanently increased
      hippocampal type II, glucocorticoid receptor binding. Relative to H females, NH
      females showed increased basal corticosterone levels in later life and
      hypersecreted corticosterone following stress at all ages examined. Both effects
      are similar to those reported in males. However, unlike males, H and NH females
      did not differ in corticosterone levels achieved during stress, a finding that
      may be related to sex-dependent effects of handling on pituitary transcortin
      receptors. There were no differences in hippocampal neuron density in 6-month-old
      animals. However, the older NH animals showed considerable neuron loss in the CA1
      and CA3 hippocampal cellfields. There was little or no neuron loss in the H
      animals. Finally, the NH animals exhibited age-related spatial memory
      impairments, such that by 24 months of age the performance of the NH females was
      profoundly worse than that of the younger NHs and same-aged H animals. These data
      suggest that early handling permanently alters CNS systems that regulate
      hypothalamic-pituitary-adrenal (HPA) function, although the effect may depend on
      the gender of the animal. In both males and females, however, handling appears to
      prevent (or minimize) increased adrenal secretion in later life and to attenuate
      hippocampal cell loss and spatial memory impairments.

PMID- 2002882
TI  - Exogenous nerve growth factor stimulates choline acetyltransferase activity in
      aging Fischer 344 male rats.
AB  - The effect of age and exogenous nerve growth factor (NGF) infusion on choline
      acetyltransferase (ChAT) specific activity is examined in microdissections of
      cerebral and hippocampal cortices, and the cholinergic nuclei of the medial
      septum and diagonal band of Broca (MS/DB), the nucleus basalis magnocellularis
      (NBM), and striatum of Fischer 344 male rats. Significant, 20% losses in ChAT
      activity are found in the MS/DB and striatum of 24-month-old rats (n = 21)
      compared to 4-month-old animals, but there is no apparent loss of enzyme activity
      in the NBM. Loss of ChAT activity in the MS/DB is only observed in animals older
      than 19 months of age, while a striatal deficit is found in animals older than 7
      months. Treatment for 2 weeks with NGF at 1.2 micrograms/day results in
      significant 70% increases of ChAT activity in the MS/DB and striatum of 24-month
      old rats compared to untreated and vehicle-treated 4-month-old rats, but does not
      stimulate activity in the NBM. Sensitivity of ChAT activity in the MS/DB and
      striatum to exogenous NGF increases with age. These experiments indicate that in
      the MS/DB, NBM, and striatum of Fischer 344 male rat there is an age-associated,
      differential regulation of ChAT enzyme activity and sensitivity to exogenous NGF.

PMID- 2002883
TI  - Exercise does not modify spatial memory, brain autoimmunity, or antibody response
      in aged F-344 rats.
AB  - Old F-344 rats were given endurance training over a 10-week period on a motorized
      treadmill. This treatment resulted in substantial heart-to-body weight ratio
      increases, indicative of effective training. To determine whether endurance
      training might alter some of the known immune system and cognitive changes
      observed during aging, exercised old rats were compared to nonexercised old and
      young controls on three variables: in vivo antigen-specific immune activity,
      brain-reactive antibody formation, and spatial memory. The exercise training did
      not influence any of these measures in the old rats. Both groups of old rats
      showed poorer antibody response to a specific antigen, more brain-reactive
      antibody formation, and poorer spatial memory than the young controls. There was,
      however, a significant relationship between brain-reactive antibody formation and
      spatial memory performance, regardless of training condition.

PMID- 2002884
TI  - Differences in red blood cell choline and lipid-bound choline between patients
      with Alzheimer disease and control subjects.
AB  - The concentrations of red blood cell choline, glycerophosphocholine,
      phosphocholine and lipid-bound choline were measured in patients with Alzheimer
      disease (AD) and in normal elderly controls. Red blood cell choline in the
      Alzheimer group (41.4 +/- 9.2 nmol/ml) was significantly higher (p less than
      0.023) than in the elderly controls (18.7 +/- 2.3 nmol/ml). Red blood cell lipid
      bound choline (1387 +/- 58 nmol/ml) in the AD group was significantly lower (p
      less than 0.0022) than in the age-matched controls (1667 +/- 65), while there
      were no significant differences in glycerophosphocholine or phosphocholine.
      Plasma choline and lipid-bound choline did not differ significantly between the
      groups. The mechanisms for these changes still need further study, although the
      finding of decreased lipid-bound choline supports the concept of altered
      phospholipid metabolism in patients with AD.

PMID- 2002885
TI  - Platelet phospholipid synthesis in Alzheimer's disease.
AB  - The rates of incorporation of [3H]choline and [3H]ethanolamine into membrane
      phospholipids of platelets from 22 drug-free Alzheimer's disease patients and 18
      normal elderly controls were compared. No significant differences between groups
      were found. If alterations in lipid metabolism are involved in the
      pathophysiological processes underlying Alzheimer's disease, such alterations are
      not manifest in measures of radiolabeled base incorporation into platelet
      phospholipids.

PMID- 2002886
TI  - Aging and Alzheimer's disease: protease inhibitors in cerebrospinal fluid.
AB  - Recent advances suggested that proteases and their inhibitors could be implicated
      in the genesis and/or maturation of insoluble deposits associated with
      Alzheimer's disease (AD). This study was designed to measure the level of alpha 1
      antichymotrypsin (ACT) and alpha 1-antitrypsin (AT) in cerebrospinal fluid (CSF)
      of patients with AD and nondemented humans at various ages. Our analysis failed
      to demonstrate a significant relationship between inhibitor content and disease.
      However, a positive correlation was observed between age and the ACT level for
      the normal control group. Such observation suggests a specific association of ACT
      with the mechanisms of brain aging.

PMID- 2002887
TI  - The role of environmental factors in neurodegenerative disorders.

PMID- 2002888
TI  - American Academy of Neurology, 43rd annual meeting program. Boston,
      Massachusetts, April 21-27, 1991.

PMID- 2002889
TI  - The United States Army Medical Department in low-intensity conflict.
AB  - For 30 years, in rural Texas, rural Kentucky, and in the Army, I have observed a
      variety of efforts aimed at changing people's health. Recently I participated in
      one large effort (USNS MERCY), commanded a second (MED EL, JTF-Bravo, Honduras),
      was "neighbor" and visitor to a third (Medical Assistance Team in El Salvador),
      and had staff level interface with others (Ahuas Tara 88, Fuertes Caminos 88, and
      Special Operating Forces Humanitarian Assistance Team, all in Honduras). This
      article speaks to the philosophies which I believe drive, or should drive, these
      initiatives. Other articles will explore individual iterations.

PMID- 2002890
TI  - Oral-activated charcoal. An old friend revisited.

PMID- 2002891
TI  - HMOs: survival of the fittest.

PMID- 2002892
TI  - Obstruction of the inferior vena cava.

PMID- 2002893
TI  - Prescribing under OBRA. Myth and reality.
AB  - The Omnibus Budget Reconciliation Act (OBRA) aims to reduce unnecessary
      psychotropic drugs in nursing facilities, bringing prescribing practices under
      scrutiny. Yet, OBRA can be adapted by physicians.

PMID- 2002894
TI  - One-handed wound approximator.

PMID- 2002895
TI  - HMOs today.

PMID- 2002896
TI  - Mental illness in the late 19th century at Elizabeth General Hospital.
AB  - In 1880, Elizabeth General Hospital and Dispensary opened its doors. The Hospital
      records, the daily newspapers of Elizabeth, and the medical journals often noted
      psychiatric symptomatology and concepts.

PMID- 2002897
TI  - Tribute to Jenny.

PMID- 2002899
TI  - Yes, you can land the job you really want! Here's how....

PMID- 2002898
TI  - Recognizing pulmonary embolism.

PMID- 2002900
TI  - 3 ways to manage stress.

PMID- 2002901
TI  - Mrs. Grant's last party.

PMID- 2002902
TI  - A.I.D.S. update. Testing health care professionals for H.I.V.

PMID- 2002903
TI  - How to evaluate platelet values.

PMID- 2002904
TI  - Methotrexate for rheumatoid arthritis.

PMID- 2002905
TI  - Action stat! Autonomic dysreflexia.

PMID- 2002906
TI  - Glucose testing at home.

PMID- 2002907
TI  - Interhospital transfer. How to prepare your patient.

PMID- 2002908
TI  - An interview with Joy Ufema, RN, MS. Meeting the challenge of a dying patient.

PMID- 2002909
TI  - The death of a duke.

PMID- 2002910
TI  - Avoiding errors caused by drug suffixes.

PMID- 2002911
TI  - She could have sung all night.

PMID- 2002912
TI  - Getting your patient ready for a nuclear medicine scan.

PMID- 2002913
TI  - Making codes as easy as ABC ... CD.

PMID- 2002914
TI  - How to use an automated vital signs monitor.

PMID- 2002915
TI  - Boost your self-confidence.

PMID- 2002916
TI  - Investigating postoperative muscular pain.

PMID- 2002917
TI  - What I didn't see before.

PMID- 2002918
TI  - Carbamazepine for trigeminal neuralgia and pain.

PMID- 2002919
TI  - P-A-C-E yourself: tips on time management.

PMID- 2002920
TI  - 6 steps to becoming more assertive.

PMID- 2002921
TI  - They don't all live happily ever after.

PMID- 2002923
TI  - How to irrigate the eye.

PMID- 2002922
TI  - A.I.D.S. update.

PMID- 2002924
TI  - Action stat! Left ventricular cannulation.

PMID- 2002925
TI  - Assessing and managing a gastric ulcer.

PMID- 2002926
TI  - Alternative for alcohol withdrawal.

PMID- 2002927
TI  - Silent messenger.

PMID- 2002928
TI  - Are you at risk for hepatitis B?

PMID- 2002929
TI  - Helping ostomy patients manage medications.

PMID- 2002930
TI  - Job satisfaction and retention. Insights for the '90s. Part 1.

PMID- 2002931
TI  - Ethel needed a friend.

PMID- 2002932
TI  - Plasmapheresis to treat lupus.

PMID- 2002933
TI  - Synthetic surfactant. Giving premature infants a better chance for survival.

PMID- 2002934
TI  - Good-bye, Karen.

PMID- 2002935
TI  - Medical/surgical nursing, Part 2.

PMID- 2002936
TI  - Bringing Theresa home.

PMID- 2002937
TI  - Assessing confusion in an elderly patient.

PMID- 2002938
TI  - Medicare reduces targets for physician payments.

PMID- 2002939
TI  - A systems approach to the management of nursing services. Part I: Introduction.

PMID- 2002940
TI  - Rural healthcare: new opportunities for nurses.

PMID- 2002941
TI  - Securing your system from hackers and other hazards.

PMID- 2002942
TI  - The nurse's role as an expert witness.

PMID- 2002943
TI  - Community-based nursing case management pays off.

PMID- 2002944
TI  - Coordinated care in a community hospital.

PMID- 2002945
TI  - Introducing and accounting for RN case management.

PMID- 2002946
TI  - RN-LPN Teams: toward unit nursing case management.

PMID- 2002947
TI  - Leaders: the organization's pacemakers.

PMID- 2002948
TI  - A consortium introduces RN case management regionwide.

PMID- 2002949
TI  - Verbal abuse nationwide, Part II: Impact and modifications.

PMID- 2002950
TI  - Verbal abuse of nurses and non-nurses.

PMID- 2002951
TI  - Expectations and responsibilities of the nursing director role.

PMID- 2002952
TI  - Managing the budget with a fluctuating census.

PMID- 2002953
TI  - Patient education for total hip replacement.

PMID- 2002954
TI  - Later always arrives sooner than you think.

PMID- 2002955
TI  - Toward safer nursing practice.

PMID- 2002956
TI  - The geriatric nurse specialist role: a new model.

PMID- 2002957
TI  - Capturing nursing dollars.

PMID- 2002958
TI  - Educating managers on-site and conveniently.

PMID- 2002959
TI  - Analysis of time-activity curves related to myocardial metabolism. The case of
      123I-heptadecanoic acid.
AB  - Time-activity curves are frequently used in the external assessment of the
      kinetics of radiolabelled non-esterified fatty acids. Analysis of time-activity
      curves is accomplished by fitting an analytical curve through the data points of
      the time-activity curve, resulting in two or more parameters of the curve fit.
      Before interpreting the results of curve fitting, the precision of each of the
      parameters has to be determined. In the present study the precision of the
      parameters of monoexponential plus constant curve fit of time-activity curves
      after administration of 123I-heptadecanoic acid was assessed for an acquisition
      time of 75 min. Two parameters were used, the T1/2 of the monoexponential and the
      ratio A/A+C, where A is the amplitude of the monoexponential and C the constant.
      A model study was used to assess the precision of the parameters of curve
      fitting. The precision of the parameters was calculated for wide ranges of the
      T1/2 (0-60 min), A/A+C (0-100%) and the noise content of the time-activity curve.
      The results are presented as the 10th and 90th percentiles.

PMID- 2002960
TI  - Wipe tests to assess 99Tcm surface contamination: effects of surface type, swab
      type and chemical form.
AB  - The efficacy of wipe tests for assessing 99Tcm surface contamination was
      measured. Four types of surface were contaminated with four radiopharmaceuticals
      and wiped using four types of swab. The fraction of activity removed was measured
      by direct monitoring for each combination of surface, pharmaceutical and swab.
      The results obtained showed that wipe tests are neither accurate nor precise.
      Observed wipe efficacies differed greatly from the customary assumption that 10%
      of the activity is removed by wiping. Detergent soaked swabs gave a mean efficacy
      of 40%, although with considerable variation (coefficient of variation 49%).
      Using these swabs alone the surface type affected efficacy by almost a factor
      three (floor tile mean efficacy 20%, plastic laminate mean efficacy 57%). In
      principle this effect might be compensated for by using correction factors
      according to the surface being swabbed. However, the pharmaceutical type will
      generally be unknown, and this also affected efficacy by almost a factor of two
      (eluate mean efficacy 29%, macroaggregated albumin 53%). Overall the results
      suggest that wipe tests can be used to detect contamination but are unreliable
      for quantification.

PMID- 2002961
TI  - Quantitative evaluation of four 99Tcm colloids for bone marrow scintigraphy using
      single photon emission computed tomography.
AB  - Colloids used for bone marrow scintigraphy are also taken up in the liver and
      spleen. The liver activity in particular hampers interpretation of the study. In
      this study, four small-sized commercial colloids labelled with 99Tcm were
      compared for bone marrow uptake relative to the liver, spleen and background
      activity. Three human albumin colloids (Microlite, E.I. du Pont de Nemours & Co;
      Solco Nanocoll, Solco Nuclear; TCK-9, International CIS) and one antimony
      sulphide colloid (TechneScan Sb2S3, Mallinckrodt Diagnostics) were compared. The
      study was performed in patients routinely referred for liver/spleen scintigraphy
      who had a normal result. Each examination was carried out using single photon
      emission computed tomography. After correction for attenuation and scattering of
      photons, the activity of the bone marrow of the lumbar spine was related to the
      liver, spleen and background activity. The bone marrow/liver activity quotient of
      Solco Nanocoll and TCK-9 was almost twice the value for Microlite and TechneScan
      Sb2S3. The bone marrow/spleen quotient was almost four times higher and the bone
      marrow/background quotient almost twice as high for Solco Nanocoll as for the
      other three colloids, between which there were no significant differences.

PMID- 2002962
TI  - Development of macromolecular Sn(II) complex for preparation of 99Tcm
      radiopharmaceuticals.
AB  - Macromolecular Sn(II) complex (R-Sn) was developed using a chelating resin
      containing aminophosphonic acid groups as a reducing agent of 99Tcm(VII) in the
      preparation of 99Tcm radiopharmaceuticals. Since Sn(II) was bonded strongly to
      the resin by chelation, release of Sn from R-Sn was rarely observed in saline
      solution. 99Tcm labelling with a yield greater than 90% was performed by mixing R
      Sn, 99Tcm pertechnetate solution and a ligand, such as human serum albumin and
      diethylenetriamine pentaacetic acid, for a short time. The 99Tcm
      radiopharmaceuticals were almost free from Sn(II) and the reducing activity of R
      Sn was quite stable despite long-term storage without any special care.

PMID- 2002963
TI  - Detection of occult hepatic metastases using the hepatic perfusion index.

PMID- 2002964
TI  - Detection of occult hepatic metastases using the hepatic perfusion index. Is the
      hepatic perfusion index clinically useful?

PMID- 2002965
TI  - Exchange of nuclear medicine image files.

PMID- 2002966
TI  - Radiolabelled monoclonal antibodies in oncology. II. Clinical applications in
      diagnosis.
AB  - The clinical applications of this approach to the management of patients with
      ovarian cancer and of patients with colorectal cancer are emphasized. The
      introduction of stable 99Tcm labelling of monoclonal antibodies means that
      radioimmunoscintigraphy is able to become routinely available in nuclear medicine
      departments.

PMID- 2002967
TI  - A comparison of same day and separate day injection protocols for myocardial
      perfusion SPECT using 99Tcm-MIBI.
AB  - Three dose administration protocols for 99Tcm-MIBI were applied to groups of 15
      patients with known or suspected ischaemic heart disease. Firstly, injections
      were given on consecutive days, with 300 MBq at rest and 500 MBq 24 h later at
      exercise. Secondly, both injections on the same day with 200 MBq at rest followed
      1.5 h later by 1000 MBq during exercise. Finally, both injections on the same day
      with 200 MBq at rest followed 1.5 h later by 600 MBq during exercise. The
      diagnostic accuracy was significantly better when the administrations were on
      separate days than when given on the same day. There was no difference in
      diagnostic accuracy between the two same day protocols. The same day protocols
      gave a significantly higher false negative reporting rate than the separate day
      protocol.

PMID- 2002968
TI  - Advanced maternal age as a risk factor for cesarean delivery.
AB  - The rate of delivery by cesarean has increased steadily in the United States
      since the 1970s. The reasons for this increase are not fully established.
      Improved diagnosis of maternal and fetal complications, medicolegal concerns, and
      the changing age composition of childbearing women have been cited as
      contributing factors. To assess whether advanced maternal age by itself is an
      indicator for a primary cesarean delivery, we analyzed data from the vital
      records of all female residents of King County, Washington 35 years and older (N
      = 2985) who had a live singleton birth in 1986 or 1987. These women were compared
      with a sample of women 20-29 years old (N = 6140) who gave birth in the same time
      period and geographic area. Primiparous and multiparous women 35 years and older
      were at a similar increased risk of cesarean (relative risk = 1.6, 95% confidence
      interval 1.1-2.4). Primiparous women of all ages experienced more complications
      of pregnancy and labor and higher cesarean delivery rates. However, among
      primiparous mothers with no recorded complications, older women were at
      significantly increased risk of cesarean birth (relative risk = 2.5, 95%
      confidence interval 1.8-3.5). This analysis suggests that advanced maternal age
      alone may influence a physician's decision regarding method of delivery, thereby
      placing some older women at an unnecessary risk of cesarean.

PMID- 2002970
TI  - Toluene abuse during pregnancy: obstetric complications and perinatal outcomes.
AB  - Toxic vapor abuse during pregnancy was found to be associated with increased
      maternal and fetal morbidity. Toluene-induced renal tubular acidosis occurred in
      over half of these women and was clustered among long-duration abusers. The renal
      acidosis placed the mother at risk for hypokalemia, with associated cardiac
      dysrhythmias and rhabdomyolysis. Beta-mimetics and intravenous fluid for preterm
      labor therapy potentially exacerbated the electrolyte abnormalities. Among 21
      newborns exposed to toluene in utero, preterm delivery, perinatal death, and
      growth retardation were significantly increased. Delivery during uncorrected
      maternal acidosis further compromised these infants. As children, growth
      retardation and developmental delay were common findings. Recognition of the
      unique obstetric and medical characteristics of the toluene-abusing woman is
      needed if complications are to be averted and perinatal outcomes improved.

PMID- 2002969
TI  - The effect of cesarean delivery on birth outcome in very low birth weight
      infants. National Institute of Child Health and Human Development Neonatal
      Research Network.
AB  - To determine whether cesarean delivery is associated with a better outcome than
      vaginal delivery for infants weighing less than 1500 g (very low birth weight),
      we examined neonatal mortality and the incidence of intraventricular hemorrhage
      (IVH) in 1765 very low birth weight inborn infants admitted to seven neonatal
      intensive care centers. The cesarean rate was 32.5% for infants weighing 501-750
      g and 52.4% for infants weighing 751-1000 g. The neonatal death rate was 53.1%
      for infants weighing 501-750 g delivered by cesarean, compared with 64.3% for
      vaginally born infants (P = .046). However, for infants weighing 1001-1250 g, the
      neonatal death rate for infants delivered by cesarean was 14.4%, compared with
      7.8% for infants born vaginally (P = .02). The incidence of IVH was significantly
      lower in infants born by cesarean than in those born vaginally only in the 1251
      1500-g birth weight interval (11.8 versus 18.9%; P = .03). Compared with women
      delivering vaginally, those delivered by cesarean were more likely to attain a
      higher mean gestation, to have preeclampsia, and to have a breech presentation,
      and less likely to be in labor. After adjusting by logistic regression for
      gestational age, preeclampsia, breech presentation, presence or absence of labor,
      and for center effects, the odds ratio for neonatal death was 1.00 (95%
      confidence interval 0.71-1.41); for IVH, the odds ratio was 0.85 (95% confidence
      interval 0.61-1.19). These data suggest that after accounting for certain
      maternal and fetal factors, cesarean delivery is not associated with a lower risk
      of either mortality or IVH.

PMID- 2002971
TI  - Calcium excretion in preeclampsia.
AB  - Recent studies have suggested that preeclampsia is associated with hypocalciuria.
      We compared 24-hour urine data from 143 obstetric patients: 33 with preeclampsia,
      58 normotensives, and 52 patients with gestational hypertension. The mean
      maternal age, race, and parity of these three groups did not differ
      significantly. The patients with preeclampsia had significantly less excretion of
      total calcium (129.7 +/- 18.7 mg/24 hours) (mean +/- SEM) than normotensives
      (283.9 +/- 12.3) or those with gestational hypertension (233.2 +/- 22.3) (P =
      .0001). The mean arterial pressure and excretion of total protein were
      significantly increased in the preeclampsia group (P = .0001). Using the receiver
      operator curve, a urine calcium threshold of 12 mg/dL was chosen as predictive
      for the development of preeclampsia, with a sensitivity of 85%, specificity of
      91%, and positive and negative predictive values of 85 and 91%, respectively.
      Urinary calcium levels below 12 mg/dL may help distinguish preeclampsia from
      other hypertensive disorders of pregnancy.

PMID- 2002972
TI  - Hypertension during pregnancy in insulin-dependent diabetic women.
AB  - Insulin-dependent diabetic patients are at increased risk for hypertensive
      disorders of pregnancy. This study was designed to study prospectively the rate
      of pregnancy-induced hypertension (PIH) in 175 insulin-dependent diabetic
      pregnancies (88 White classes B-C, 87 classes D-RT). Pregnancy-induced
      hypertension was defined as two or more occurrences after 20 weeks' gestation of
      a mean arterial pressure (MAP) of 105 mmHg or greater or an increase of 20 mmHg
      or greater from the baseline MAP. The rate of PIH in the diabetic population was
      15.4% and was significantly associated with nulliparity, poor glycemic control in
      the first and second trimesters, and advanced White class. Neonatal outcome was
      not significantly altered in the presence of PIH. We speculate that improved
      glycemic control throughout pregnancy might reduce the rate of this complication
      in diabetic patients.

PMID- 2002973
TI  - Surgical glove perforation in obstetrics.
AB  - Perforation of surgical gloves places the obstetrician at risk for blood-borne
      infectious diseases. Seven hundred fifty-four surgical gloves used in vaginal and
      cesarean deliveries and postpartum tubal ligations were examined for evidence of
      perforation by the air inflation-water submersion technique. The overall glove
      perforation rate was 13.3%, with 62% of the perforations remaining unrecognized
      during the surgical procedure. The majority of perforations occurred on the
      fingers of the nondominant hand. Multivariate analysis with logistic regression
      indicated that cesarean delivery (odds ratio 3.52), any vaginal laceration or
      episiotomy (odds ratio 4.95), and chief resident status (odds ratio 3.00) were
      the major risk factors for surgical glove perforation. Surgical technique by
      assistants, especially in complex cases, is as important as that of the primary
      surgeon in regard to glove perforations.

PMID- 2002974
TI  - Magnetic resonance imaging of fetuses with intracranial defects.
AB  - Thirteen women whose fetuses had intracranial defects on ultrasound examination
      were offered magnetic resonance imaging (MRI) without charge. All fetuses were
      paralyzed with pancuronium before the study, which lasted approximately 1 hour.
      With the mother in the left lateral decubitus position to minimize transmitted
      maternal aortic pulsation, T1-weighted images were obtained using a Picker 0.5
      tesla superconductive unit. Magnetic resonance imaging provided excellent detail
      of intracranial anatomy in all cases. In four of the 13 fetuses, the MRI
      diagnosis differed from that of ultrasound and ultimately proved correct. In
      another three, MRI added greatly to the ultrasound diagnosis by delineating
      intracranial anatomy more precisely. In the remaining six cases, MRI confirmed
      the ultrasound impression. For circumstances in which the ultrasound diagnosis is
      unclear or antenatal intervention might require exact knowledge of anatomical
      detail, the additional information provided by MRI may justify its cost.

PMID- 2002975
TI  - Aggressive therapeutic amniocentesis for treatment of twin-twin transfusion
      syndrome.
AB  - Acute severe twin-twin transfusion syndrome occurs in about 1% of monochorionic
      twin gestations. In the most severe form, acute hydramnios develops in the
      recipient twin's sac and fetal hydrops may be present. The donor twin is anemic
      and oligohydramnios is present, so that the donor appears "stuck" in a cocoon
      made by its adherent amnion. In this report, aggressive therapeutic amniocentesis
      restored amniotic fluid volume to normal in both sacs in all pregnancies. Fetal
      hydrops resolved in three of five (60%) of the fetuses affected. Pregnancy was
      extended a mean 80 +/- 33 days (+/- 2 SD) and perinatal survival was 79%. These
      findings contrast dramatically with the virtual 100% mortality reported in the
      literature with no therapy. Repeated aggressive amniocentesis effectively
      reversed the physiology of twin-twin transfusion syndrome and should be the
      treatment of choice for acute hydramnios, which previously had no recommended
      therapy.

PMID- 2002976
TI  - Endocrine pancreatic function in growth-retarded fetuses.
AB  - Maternal-fetal glucose gradient and fetal plasma glucose, insulin, and glucagon
      were measured in 63 fetuses: 34 controls and 29 with growth retardation (nine
      with and 20 without end-diastolic frequencies in the umbilical artery). Maternal
      fetal glucose gradient and fetal glucagon levels were higher in the growth
      retarded group than in controls (P less than .001), whereas fetal insulin and
      glucose concentrations were lower (P less than .001). Although maternal-fetal
      glucose gradient, fetal glucose, and insulin concentrations were similar among
      the growth-retarded fetuses, fetuses without end-diastolic frequencies in the
      umbilical artery had higher fetal glucagon levels (P = .01) than those with end
      diastolic frequencies. In growth-retarded fetuses, the increase in fetal glucagon
      might reflect a compensatory response to hypoglycemia and appears to be a better
      index of fetal compromise than is glucose or insulin.

PMID- 2002977
TI  - Sequential invasive assessment of fetal renal function and the intrauterine
      treatment of fetal obstructive uropathies.
AB  - Persistent fetal lower urinary tract obstruction carries a very poor prognosis
      secondary to damaged renal capacity and oligohydramnios, with its related
      pulmonary hypoplasia. Several attempts in the past several years to divert
      urinary flow via an intrauterine shunt have generally been disappointing,
      primarily because of poor patient selection. In this study we report our
      experiences with aggressive decompression of megacystis in 11 patients, the value
      in selected cases of sequential evaluations of fetal urine biochemistry, and the
      success of intrauterine bladder shunting procedures in appropriately chosen
      patients. Our data suggest that a single fetal urine determination may be
      insufficient to declare irreversible damage. Following decompression, improvement
      in urine biochemistry or its lack may be more likely representative of ultimate
      outcome. Decompression by either needle aspiration or intrauterine shunting is
      warranted in carefully selected cases and can save fetuses that are otherwise
      very likely doomed.

PMID- 2002978
TI  - Association of umbilical venous with inferior vena cava blood flow velocities.
AB  - The fetal cardiac and placental circulations are interconnected through the
      umbilical venous and arterial vasculature. We hypothesized that alterations in
      umbilical venous blood flow velocities are present in fetuses with abnormal
      umbilical arterial circulation, and further, that changes in inferior vena cava
      blood flow velocities occur with, and might explain, these variations in
      umbilical venous blood flow velocities. Umbilical venous and inferior vena cava
      blood flow velocities were examined in 15 normal fetuses and in 59 fetuses with
      abnormalities that included absent end-diastolic umbilical artery blood flow
      velocities (N = 21) or abnormal heart rates (N = 27). Inferior vena cava
      velocities were also analyzed in 11 other fetuses with anomalies or known growth
      or placental abnormalities who had abnormal umbilical venous blood flow
      velocities. In normal fetuses, variations in umbilical venous velocities occurred
      during fetal activity or with fetal breathing; however, no variation in velocity
      corresponded with heart rate. Eleven of 21 fetuses with absent end-diastolic
      velocities in the umbilical artery demonstrated decreases in umbilical venous
      velocities ("venous pulsations") during arterial diastole. Blood flow velocities
      in the reverse direction, from the right atrium into the inferior vena cava with
      atrial contraction, were significantly greater in these fetuses than in those
      without umbilical venous pulsations (27.5 +/- 14.9% and 7.5 +/- 5.7% of total
      forward flow velocity, respectively; P less than .001). Venous pulsations were
      also seen in fetuses with abnormally fast or slow heart rates; reverse flow with
      atrial contraction in the inferior vena cava was likewise greater than normal in
      these fetuses.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2002979
TI  - Use of various epithelial tumor markers and a stromal marker in the assessment of
      cervical carcinoma.
AB  - The epithelial cell tumor markers squamous cell carcinoma antigen, CA 125, CA 15
      3, and TAG 72, and the aminoterminal propeptide of type III procollagen, an
      indicator of collagen metabolism, were evaluated in 111 cervical carcinoma
      patients. Squamous cell carcinoma antigen was pathologic in 47%, aminoterminal
      propeptide of type III procollagen in 40%, CA 125 in 13%, CA 15-3 in 30%, and TAG
      72 in 9% of the 91 patients with squamous cell carcinoma. The squamous cell
      carcinoma antigen, aminoterminal propeptide of type III procollagen, and CA 125
      correlated with the clinical stage. The predictive value of a pathologic squamous
      cell carcinoma antigen was 78% and that of a negative result 68%. Squamous cell
      carcinoma antigen and aminoterminal propeptide of type III procollagen further
      increased the detection rate by approximately 20% from that obtained by squamous
      cell carcinoma antigen alone. In 16 patients with advanced disease, squamous cell
      carcinoma antigen correlated with the behavior of the disease in eight,
      aminoterminal propeptide of type III procollagen in nine, and CA 125 in six
      patients. Pathologic squamous cell carcinoma antigen, CA 125, CA 15-3, TAG 72,
      and aminoterminal propeptide of type III procollagen appeared in 11, 32, 31, 31,
      and 47% of 19 patients with adenocarcinoma, respectively. Squamous cell carcinoma
      antigen is clinically useful in squamous cell carcinoma but poor in
      adenocarcinoma, for which the other markers are better. Squamous cell carcinoma
      antigen, CA 125, and aminoterminal propeptide of type III procollagen may be used
      for monitoring the behavior of advanced squamous cell carcinoma.

PMID- 2002980
TI  - Ultrasonic surgical aspiration in the treatment of vulvar disease.
AB  - Ultrasonic surgical aspiration is a useful technique for safe and accurate tissue
      removal. This study was conducted to evaluate its role in noninvasive vulvar
      disease. From December 1988 to March 1990, 27 patients underwent ultrasonic
      surgery; nine patients had vulvar intraepithelial neoplasia (VIN) and 18 had
      condylomata acuminata. All surgical procedures were done under general
      anesthesia, with two patients requiring hospitalization for perineal care and
      pain control after extensive vulvar surgery. Recurrent or persistent disease
      occurred in four patients with condylomata acuminata and in two with VIN, with a
      mean follow-up of 50 weeks. Reepithelialization was completed within 5 weeks and
      no patients developed vulvar scarring. Adequate samples for histopathologic
      review were obtained in 26 patients. Identical histologic grading occurred in all
      13 patients who had preoperative vulvar biopsies and an adequate aspiration
      specimen. Ultrasonic surgery permits precise and rapid removal of epithelial
      lesions with rapid healing, minimal patient discomfort, excellent cosmetic
      results, and histopathologic documentation.

PMID- 2002981
TI  - Radical vulvectomy with partial rectal resection and temporary colostomy as
      primary therapy for selected patients with vulvar carcinoma.
AB  - The patient with carcinoma of the vulva may present with tumor involvement of the
      perirectal area. Traditional treatment has often involved ultraradical therapy
      including a radical vulvectomy with posterior or total pelvic exenteration in an
      effort to obtain adequate surgical margins. Five-year survival rates for these
      patients range from 20-50%, and major operative morbidity as well as
      psychological problems are associated with this extensive surgery. Five patients
      treated for a locally advanced vulvar carcinoma involving the perirectal area
      were thought to be candidates for a rectum-sparing procedure. They underwent a
      radical vulvectomy, bilateral inguinal lymphadenectomy, partial rectal resection,
      and a diverting colostomy. Four of the five patients agreed to a colostomy
      closure 6 months after their primary therapy; these four patients have resumed
      normal bowel function. All patients remain clinically free of tumor.

PMID- 2002982
TI  - Antigen CA 19-9: presence in mucosa of nondiseased mullerian duct derivatives and
      marker for differentiation in their carcinomas.
AB  - CA 19-9, a side branch of the Lewis blood group system, is a sialylated Lewis A
      antigen that is highly expressed by many adenocarcinomas of the digestive tract.
      The mullerian duct-derived mucosa of the uterus and fallopian tubes also
      synthesizes Lewis blood group antigens. To test whether the expression of CA 19-9
      is enhanced in carcinomas of mullerian duct origin, we performed
      immunohistochemical staining for CA 19-9 in normal tissues from 33 women and in
      adenocarcinomas from 88 patients. In the normal uterine cervix, CA 19-9 was
      expressed in the cytoplasm of scattered glandular cells in 26 of 29 specimens. It
      was observed in the apical regions of mucosal cells in six of 26 normal
      endometrial samples and two of 13 normal fallopian tube specimens. These results
      are consistent with the presence of antigen CA 19-9 on a secretory product of the
      nondiseased mucosa of the mullerian duct. In adenocarcinomas of the endocervix,
      endometrium, and fallopian tubes, CA 19-9 was found in seven of 11, 57 of 71, and
      five of six samples, respectively. Progressive loss of differentiation was
      accompanied by disruption of subcellular localization of CA 19-9 and its
      secretion toward the glandular lumina. In well-differentiated regions of tumors,
      the antigen was detected mainly at the luminal surface of cancerous glands,
      whereas the staining was mostly cytoplasmic or vacuolar in less differentiated
      areas. The degree of CA 19-9 expression was inversely related to tumor
      differentiation (P less than .001).

PMID- 2002983
TI  - The long-term effectiveness of hysteroscopic treatment of menorrhagia and
      leiomyomas.
AB  - One hundred fifty-six of 177 patients admitted to the St. Luke's/Roosevelt
      Hospital Center between November 1973 and November 1988 for hysteroscopic
      treatment of menorrhagia and/or uterine leiomyomas were followed for long-term
      complications and necessity for repeat surgery. Ninety-four patients underwent
      submucous resection alone and 62 patients underwent endometrial ablation with or
      without submucous resection. Among the submucous-resection group, 24.5% reported
      late postoperative problems and 15.9% underwent further surgery. After 9 years of
      followup, 83.9% of the patients had not required further surgery. Among the
      ablation group, 22.5% experienced recurrence of increased bleeding and 8.1% had
      another surgical procedure. After 6 years of follow-up, 91.3% of the patients had
      not required further surgery. Twenty-one patients became pregnant after submucous
      resection, with 18 infants delivered. No patients who underwent endometrial
      ablation became pregnant. This modality of treatment appears to be effective over
      the long term, although effectiveness appears to diminish with time.

PMID- 2002984
TI  - Elevated serum testosterone, hirsutism, and virilism associated with combined
      androgen-estrogen hormone replacement therapy.
AB  - Nine postmenopausal women with symptoms and signs of androgen excess due to long
      term use of an injectable androgen-estrogen combination were studied
      retrospectively. Cosmetically disturbing hirsutism was the major complaint in
      eight subjects. Other symptoms included hot flushes, decreased libido, mood
      changes, depression, and postmenopausal bleeding in the one patient with an
      intact uterus. Seven women had clitorimegaly; the clitoral index ranged from 45
      120 mm2 (normal up to 35). Serum total testosterone levels were elevated in eight
      women, ranging from 5.7-14.9 nmol/L (normal up to 2.43). The androgen-estrogen
      combination was discontinued and oral or transdermal estrogen replacement was
      instituted. In five women followed serially for 16-24 months, elevated
      testosterone levels required 12-20 months to return to the normal premenopausal
      range.

PMID- 2002985
TI  - Routine human immunodeficiency virus infection screening in unregistered and
      registered inner-city parturients.
AB  - Women who receive little or no prenatal care are at increased risk of adverse
      pregnancy outcome. Although many of these women are disadvantaged and presumably
      at increased risk for human immunodeficiency virus (HIV) infection, few data are
      available to describe risk behaviors and infection prevalence in this population.
      To better characterize HIV infection in unregistered inner-city parturients in
      Atlanta, we offered routine voluntary screening for HIV antibody and requested
      HIV risk-behavior profiles on all unregistered and registered parturients seen at
      Grady Memorial Hospital from July 1, 1987 to June 30, 1988. Of the 834
      unregistered and 7356 registered parturients screened, significantly more
      unregistered parturients were seropositive on enzyme-linked immunosorbent assay
      and Western blot testing, 12 (1.4%) versus 26 (0.4%) (odds ratio 4.06; 95%
      confidence interval 1.93-8.43). Five unregistered and 15 registered parturients
      were seropositive by repeat enzyme-linked immunosorbent assay testing but were
      Western blot-negative. Significantly more unregistered parturients reported both
      a history of intravenous drug use, 4.4 versus 1.5% (odds ratio 3.09; 95%
      confidence interval 2.10-4.54), and crack cocaine use, 3 versus 0.8% (odds ratio
      3.96; 95% confidence interval 2.42-6.44). Significantly more unregistered
      parturients acknowledged risk factors for HIV infection, 14.3 versus 9.9% (odds
      ratio 1.46; 95% confidence interval 1.19-1.80). Nearly all registered and 86% of
      unregistered parturients consented to HIV testing. Nearly all parturients
      completed HIV risk-behavior questionnaires. These data suggest that unregistered
      inner-city parturients in Atlanta are at greater risk of being HIV-infected and
      are more likely to report risk behaviors for infection.

PMID- 2002986
TI  - The epidemiology of group B streptococcal colonization in pregnancy. Vaginal
      Infections and Prematurity Study Group.
AB  - Risk factors for cervicovaginal group B streptococcal colonization at 23-26
      weeks' gestation were studied in 7742 women participating in the Vaginal
      Infections and Prematurity study. The prevalence of group B Streptococcus was
      18.6%, and was greatest in (predominantly Caribbean) Hispanics from New York
      City, followed by blacks, whites, and other (predominantly Mexican) Hispanics.
      Group B Streptococcus was more common among older women and women of lower
      parity, and less common among women living with their partner compared with those
      living alone. Current smoking was associated with a decreased risk of
      colonization, and group B Streptococcus was less common among women with more
      education. Increased risk was seen only with extreme increases in sexual activity
      including both frequent intercourse and multiple partners during the previous
      year. The risk of colonization was greater when there was concurrent colonization
      with Candida sp, but group B Streptococcus was not associated with carriage of
      Chlamydia trachomatis, Ureaplasma urealyticum, Trichomonas vaginalis, and
      Mycoplasma hominis. External genital erythema and scaling, purulent vaginal
      discharge, and pH greater than 5 were associated with increased colonization.
      Although these associations can raise the clinical index of suspicion for group B
      streptococcal colonization in a given patient, the study data did not enable us
      to select a small group of women with a very high probability of colonization. We
      conclude that selective screening is not useful in detecting group B
      streptococcal colonization in pregnancy.

PMID- 2002987
TI  - No effect of experimental noise exposure on human pregnancy.
AB  - The effect of experimental noise exposure (15 minutes of 90-dB white noise via
      headphones) was examined on systolic, diastolic, and mean arterial pressures;
      heart rate; and stress hormones (ACTH, cortisol, prolactin, epinephrine, and
      norepinephrine) in normotensive and hypertensive pregnant women. No significant
      effects induced by noise exposure could be registered in these variables. Fetal
      and uterine blood circulation was also examined with a duplex pulsed Doppler
      system. No changes were seen on the fetal side as measured from the descending
      aorta in blood flow velocity (cm/second) or pulsatility or resistance indexes in
      either normotensive or hypertensive pregnancy. The only change observed was an
      increase in fetal heart rate in normotensive pregnancy. However, this increase
      could not be confirmed by cardiotocographic registration and is not clinically
      important. Uterine blood circulation was recorded from the proximal uterine
      artery on the placental side, and no effect of exposure was seen on pulsatility
      or resistance indexes.

PMID- 2002988
TI  - Fetal platelet consumption: a feature of placental insufficiency.
AB  - The involvement of fetal platelets in placental insufficiency was investigated.
      Platelet life span and the rate of platelet turnover were measured by a novel
      technique in fetuses with moderate and severe placental insufficiency and in
      controls. This procedure involves the measurement of platelet count and
      concentration of free glycocalicin in plasma. Placental insufficiency was defined
      by antenatal Doppler ultrasound analysis of the umbilical artery waveform, which
      was used to categorize the subjects according to whether their systolic-diastolic
      ratios were normal, moderately raised, or severely raised. Mean platelet life
      span in fetuses affected by placental insufficiency was only 60% of the normal
      fetal platelet life span (P less than .001). In addition, affected fetuses had a
      higher rate of platelet turnover, reflected in an elevated plasma glycocalicin
      concentration (4.06 +/- 0.19 versus 3.28 +/- 0.15 microgram/mL for severe
      placental insufficiency and control fetuses, respectively; P less than .01).
      Platelet life span did not differ between the moderate and severe placental
      insufficiency groups. We hypothesize that the observed changes in platelet life
      span and turnover result from increased platelet activation, which plays a role
      in the development of placental insufficiency.

PMID- 2002989
TI  - The relationship between fetal biophysical assessment, umbilical artery
      velocimetry, and fetal acidosis.
AB  - In a prospective study of 62 patients undergoing cesarean delivery before the
      onset of labor, fetal biophysical assessment and umbilical artery systolic
      diastolic ratios (S/Ds) were performed within 3 hours of delivery. There was a
      significant relationship between the fetal biophysical profile score and cord
      arterial as well as cord venous pH. However, there was no identifiable
      relationship between S/D and cord arterial or venous pH. The efficacies of the
      biophysical components alone (nonstress test [NST] and fetal biophysical profile)
      and in combination with S/D to predict fetal acidosis were determined. The NST
      had the best sensitivity (100%) and negative predictive value (100%). The fetal
      biophysical profile had the best specificity (91%), positive predictive value
      (62%), and overall efficiency (90%). The S/D had the lowest sensitivity (66%),
      specificity (42%), positive predictive value (16%), negative predictive value
      (88%), and overall efficiency (45%). The addition of S/D to the NST or fetal
      biophysical profile did not improve diagnostic accuracy. These data suggest that
      the NST should be used as a primary test for the antepartum detection of fetal
      acidosis, whereas the fetal biophysical profile is a reasonable adjunct test. The
      umbilical artery S/D, as determined by continuous-wave Doppler velocimetry, has
      no value as a primary method or an adjunct in the antepartum detection of fetal
      acidosis.

PMID- 2002991
TI  - Too much informed consent?

PMID- 2002990
TI  - Treatment of ectopic pregnancy by transvaginal intratubal methotrexate
      administration.
AB  - Twelve women with tubal pregnancies were treated with intratubal transvaginal
      methotrexate injection (1 mg/kg body weight). Serum beta-hCG levels decreased in
      all patients, and the resolution time from injection to undetectable beta-hCG
      levels was 14-120 days. In spite of declining serum beta-hCG and unruptured tubal
      pregnancy, two patients subsequently requested definitive treatment for their
      ectopic pregnancies and underwent surgery. Four of six women found to have a
      living embryo in their gestational sacs required a repeat methotrexate injection;
      one of these also required a local potassium chloride injection. The tubal
      pregnancies resolved in nine patients treated with methotrexate alone. During
      resolution, we noted a gradually increasing resistance index of the blood flow in
      the region of the gestation, but the tube became distended to 4.4 +/- 0.4 cm
      before gradually decreasing in size. No complications or side effects were
      encountered. These findings suggest that intratubal transvaginal methotrexate
      administration can provide a safe alternative to surgical treatment for patients
      with early unruptured tubal ectopic pregnancy. However, the presence of a living
      embryo makes the ectopic pregnancy more resistant to methotrexate treatment.

PMID- 2002992
TI  - Peripheral arterial vasodilation hypothesis of sodium and water retention in
      pregnancy: implications for pathogenesis of preeclampsia-eclampsia.
AB  - Primary peripheral arterial vasodilation with relative underfilling of the
      arterial circulation occurs in early pregnancy and leads to several consequences,
      including decreased systolic and diastolic blood pressures, enhanced cardiac
      output secondary to afterload reduction, stimulation of the renin-angiotensin
      aldosterone axis, nonosmotic stimulation of thirst and vasopressin release, and
      renal sodium and water retention with expansion of the extracellular fluid and
      plasma volume compartments. These are events known to occur in all states of
      arterial vasodilation. Pregnancy has, however, several unique features. Primary
      arterial vasodilation generally is associated with no change or a decrease in
      renal blood flow and glomerular filtration rate and failure to escape from the
      sodium-retaining effects of aldosterone. In early pregnancy, renal blood flow and
      glomerular filtration rate increase by 30-50% in parallel with the peripheral
      arterial vasodilation but before plasma volume expansion. No known vasodilator
      exhibits such a profound effect on renal hemodynamics. Vasodilating
      prostaglandins may contribute to, but cannot explain, this remarkable enhancement
      of renal hemodynamics in early pregnancy. Therefore, a highly potent, as yet
      undefined, systemic and renal vasodilator must be unique to pregnancy. The
      increased glomerular filtration rate and filtered sodium load with enhanced
      distal tubular sodium delivery allows escape from aldosterone, an effect not
      observed in other states of arterial underfilling. This vasodilator may also
      account, at least in part, for the vascular resistance to angiotensin known to
      occur in normal pregnancy. This hypothesis for the normal physiology of pregnancy
      sets the stage for understanding the pathogenesis of preeclampsia
      eclampsia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2002993
TI  - Indwelling epidural catheters for pain control in gynecologic cancer patients.
AB  - Seven patients with severe pain caused by an advanced, incurable gynecologic
      malignancy were treated with an indwelling epidural catheter connected to an
      implantable subcutaneous port through which morphine was infused. There were few
      major complications associated with insertion or maintenance of the system. The
      average usage was 60 days, although the system functioned continuously for 6
      months in one patient. Pain distribution in these women ranged from the upper
      abdomen to the lower extremities. All patients, including one with liver
      metastases, reported good to excellent pain control with the epidural narcotics.
      Two subjects with upper abdominal pain occasionally required supplemental oral
      oxycodone, but the other five patients had adequate pain relief with the epidural
      system alone. The indwelling epidural system provides excellent analgesia for
      patients with advanced, incurable gynecologic cancer.

PMID- 2002994
TI  - Maternal hemodynamics in normal and preeclamptic pregnancies: a longitudinal
      study.

PMID- 2002995
TI  - Clinical chorioamnionitis is not predicted by an ultrasonic biophysical profile
      in patients with premature rupture of membranes.

PMID- 2002996
TI  - Real-time microcomputer-based analysis of spontaneous and augmented labor.

PMID- 2002997
TI  - Managers, workers must realize need for flame-retardant clothing.

PMID- 2002998
TI  - Management should take into account the indirect costs of convalescence.

PMID- 2002999
TI  - Ergonomics will take center stage during 90s and into new century. Safety
      professional and engineers must work together to address ergonomic issues.

PMID- 2003000
TI  - Gaining the upper hand on carpal tunnel syndrome.

PMID- 2003001
TI  - Risks of radon exposure significant, but controls are relatively simple.

PMID- 2003002
TI  - City's emergency-response agencies must jointly prepare for disaster.

PMID- 2003003
TI  - Safe mouth-to-mouth resuscitation requires adjunct equipment, caution.

PMID- 2003004
TI  - Anterior lingual mandibular salivary gland defect. Evaluation of twenty-four
      cases.
AB  - Lingual mandibular salivary gland defects in the posterior part of the mandible
      are not uncommon. Analogous defects in the anterior region, however, are rare,
      and the four new cases presented in this report bring the total number of
      reported cases up to 24. The purpose of the present study was to review and
      analyze the clinical, radiographic, and histologic features of the previously
      reported cases together with those of the present study. The majority of these
      defects were located in the cuspid and/or premolar area and were diagnosed in men
      in their fifth and sixth decades of life. Almost all defects contained normal
      salivary gland tissue. The differential diagnosis, treatment, and pathogenesis of
      these defects are discussed.

PMID- 2003005
TI  - Oculocardiac reflex: pathophysiology and case report.

PMID- 2003006
TI  - Chondrosarcoma of the jaws: clinical findings, histopathology, and treatment.
AB  - Three cases of chondrosarcoma involving the jaws are presented, one in the
      maxilla and two in the mandible. The salient points of clinical presentation
      elucidated by this series of cases are that a widened periodontal ligament space
      is present in chondrosarcomas as well as in osteosarcomas, and that a slowly
      increasing diastema may be the earliest clinical sign. The most important lesson
      to be learned from the histopathology is that one should not accept a diagnosis
      of a benign cartilaginous tumor of the jaws. Treatment of these lesions should
      consist of wide surgical excision and consideration of adjunctive or palliative
      radiotherapy, especially in the maxilla. It should also be noted that recurrences
      may develop 10 to 20 years later, and follow-up should be lifelong.

PMID- 2003007
TI  - Osteomyelitis of the mandible in a patient with dysosteosclerosis. Report of a
      case.
AB  - Dysosteosclerosis is a rare bone dysplasia that has radiographic,
      histopathologic, and clinical similarities to osteopetrosis. This article reviews
      the dental findings reported in patients with dysosteosclerosis and presents the
      first reported case of osteomyelitis of the mandible in a patient with this
      disease. This is also the first report that demonstrates ankylosis of impacted
      teeth in dysosteosclerosis.

PMID- 2003008
TI  - Extensive aneurysmal bone cyst of the mandible: surgical resection and immediate
      reconstruction. A case report.
AB  - A case of extensive aneurysmal bone cyst of the mandible is described. The
      surgical defect was reconstructed immediately with two autogenous ribs and
      corallin porous hydroxyapatite. The postoperative results were good. There was no
      recurrence after 2 years of follow-up. The patient does not have any functional
      or esthetic problems.

PMID- 2003009
TI  - Third molar eruption among rural Nigerians.
AB  - Times of eruption of third molars were studied in rural Nigerian adolescents--125
      males and 133 females. Results of this study showed that the average age for the
      initial eruption of third molars was 15 years in male subjects and 13 years for
      female subjects. The incidence of eruption showed a steep rise after the age of
      16 years for male subjects and 14 years for female subjects. By the age of 19
      years, all third molars had erupted into the oral cavity. The eruption of lower
      third molars was generally ahead of the upper third molars for all age groups.
      The results of this study suggest that (1) the timing of third molar eruption is
      strongly influenced by the availability of mandibular trigone space, (2) the
      attrition and shrinkage of the dental arch, probably as the result of nonrefined
      highly fibrous diets, produce larger mandibular trigone spaces, and (3) the early
      eruption of third molars observed in the present study may be due to the nature
      of the diet used and the vigorous employment of the masticatory apparatus (from
      infancy) by the subjects examined.

PMID- 2003010
TI  - Large asymptomatic antrolith of the maxillary sinus. Report of a case.
AB  - A case of an unusually large antrolith of the maxillary sinus is presented.
      Because of the size of the mass, benign neoplasms were considered in the
      differential diagnosis. Surgery was the treatment of choice, and recurrence of
      the lesion is not expected.

PMID- 2003011
TI  - Oral manifestations of HIV infection and their management. I. More common
      lesions.
AB  - Oral lesions are common at all stages of HIV infection. This first of two
      articles reviews the clinical features and pathogenesis of common oral
      manifestations of HIV disease (candidiasis, hairy leukoplakia, Kaposi's sarcoma,
      and HIV-related periodontal disease) and considers current treatment measures.

PMID- 2003012
TI  - Oral manifestations of HIV infection and their management. II. Less common
      lesions.
AB  - This second of two articles reviews the many uncommon and rare oral lesions that
      have arisen in persons infected with human immunodeficiency virus (HIV). The
      various drug-related oral disorders of HIV disease are also considered.

PMID- 2003013
TI  - Periductal lymphocytic infiltration of salivary glands in Sjogren's syndrome with
      relation to clinical and immunologic findings.
AB  - We studied 113 patients who were suspected to have Sjogren's syndrome (SS)
      because they had dry mouth and dry eyes, and who were determined as not having
      any other autoimmune disease, to clarify the relationship of periductal
      lymphocytic infiltration of salivary glands to clinical and immunologic findings
      in relation to SS. Periductal lymphocytic infiltrations were observed in the
      labial and/or the parotid glands of 57 patients (P-group). The salivary glands of
      the other 56 patients did not demonstrate obvious histologic changes (N-group).
      The stimulated salivary flow rate of parotid glands of the patients in both the P
      and N-groups was significantly reduced when compared with healthy persons.
      However, no difference in the flow rate was observed between the P- and N-groups.
      In contrast, the percentage of patients in the P-group with keratoconjunctivitis
      sicca was significantly higher than that of patients in the N-group. Percentage
      of gamma-globulin fraction and IgG level in the sera of the patients in the P
      group were both significantly higher than those in the N-group. The percentages
      of patients who demonstrated the serum rheumatoid factor, anti-SS-A, and anti-SS
      B antibodies were also significantly higher in the P-group than in the N-group.

PMID- 2003014
TI  - Oral lichen planus.

PMID- 2003015
TI  - Congenital dermoid fistula of the lower lip.
AB  - A case of congenital dermoid fistula of the lower lip is presented. The lesion
      consisted of a major cystic portion, a proximal tubelike extension that opened in
      the lower lip as a small sinus (pit) near the left commissure, and a distal
      cordlike extension that entered into the left mental foramen. The cystic cavity
      was lined with keratinizing stratified squamous epithelium, and many sebaceous
      glands, sweat glands, and hair follicles were seen subcutaneously. The
      differential diagnosis and the pathogenesis of the lesion are also discussed.

PMID- 2003016
TI  - Lymph node metastasis in spindle cell carcinoma arising in odontogenic cyst.
      Report of a case.
AB  - The majority of primary intraosseous carcinomas of the jaws develop in
      preexisting odontogenic cysts. These tumors are usually well-differentiated
      keratinizing carcinomas with relatively good prognosis. Only two of 41 previously
      reported acceptable cases of primary intraosseous carcinomas from ex-odontogenic
      cysts were associated with cervical lymph node metastasis. Spindle cell carcinoma
      is an anaplastic dimorphic neoplasm with poor prognosis. It has a special
      predilection for the upper aerodigestive tract. This is to our knowledge the
      first report of spindle cell carcinoma developing in an odontogenic cyst.
      Cervical lymph node metastasis showing typical histologic features of spindle
      cell carcinoma was detected 8 months postoperatively. The prognostic implications
      of this finding are discussed in light of previously reported cases of
      intraosseous carcinoma arising in odontogenic cysts and of spindle cell carcinoma
      of the oral cavity.

PMID- 2003017
TI  - Referred pain of muscular origin resembling endodontic involvement. Case report.
AB  - Referred pain is common in the orofacial region and can cause considerable
      difficulties in diagnosis. Referred pain is defined as pain that is referred to a
      part of the body other than the site of origin, and as a result, severe pain may
      arise without an associated causative lesion. A muscular trigger point that
      resembled a tooth with endodontic involvement is discussed.

PMID- 2003018
TI  - Clinical study of retrograde filling with gold leaf: comparison with amalgam.
AB  - Thirty-six patients underwent endodontic surgery involving 66 teeth, with each
      root canal being retrofilled with either gold leaf or amalgam. A follow-up of
      most patients was conducted for 6 to 24 months. There was no significant
      difference in bone healing between the gold leaf-filled and amalgam-filled root
      cavities (p greater than 0.05). Gold leaf appeared to be a good alternative
      retrograde filling material and had a number of benefits over amalgam.

PMID- 2003019
TI  - Effect of x-ray tube motion on dental radiographic resolution.
AB  - X-ray tube movement during intraoral radiography is generally discouraged;
      however, the effects have not been quantified or reported. A portable x-ray tube
      head was mounted on the horizontal cross-beam of Instron model 1125 universal
      testing machine. Precise movement from 0 to 25 mm of oscillation was accomplished
      in increments of 1 mm. Four test objects were imaged during x-, y-, and z-axis
      movement of the tube head. Pinhole camera and star test pattern images were used
      to measure focal spot size for each increment of motion. Images of a resolution
      plate and a section of dry mandible were used to evaluate levels of resolution
      objectively and subjectively for each increment of motion. Results indicate that
      the size of the effective focal spot increases predictably with increasing
      increments of tube motion accompanied by a corresponding loss of resolution.
      Movement of the tube along the x- and y-axis relative to the plane of the film
      produced similar losses of resolution and were much greater than loss associated
      with z-axis movement.

PMID- 2003020
TI  - Contribution of pretreatment radiographs to orthodontists' decision making.
AB  - A study was conducted to determine the amount of diagnostic and treatment
      planning information gained by orthodontists when pretreatment radiographs are
      added to a set of orthodontic records. Thirty-nine orthodontists evaluated six
      test cases and formulated a diagnosis and treatment plan. Information was
      collected about the participants' certainty with their diagnoses and treatment
      plans, the impact of the radiographs, the number and type of radiographs that
      were selected, and the difficulty of each case. Results showed that orthodontists
      were approximately 75% confident of their diagnosis before reviewing any
      radiograph. There were 741 radiographs ordered, of which 192 produced changes to
      the diagnostic process. The lateral cephalometric radiograph was the most
      productive. Panoramic and full-mouth series were productive but provided largely
      duplicative information.

PMID- 2003021
TI  - Rheumatic disease of temporomandibular joint with development of anterior disk
      displacement as revealed by magnetic resonance imaging. A case report.
AB  - A 34-year-old woman with known rheumatic disease (psoriatic arthritis) in joints
      other than the temporomandibular joint (TMJ) developed condylar posterosuperior
      destruction and anterior disk displacement of the right symptomatic TMJ during a
      7-month period, as revealed by magnetic resonance imaging. A theory is proposed
      that destruction of the posterior attachment by pannus was the main reason for
      the disk displacement, although the pannus formation itself could not be
      depicted. Follow-up studies also indicated the potential of magnetic resonance
      imaging to demonstrate fluctuation of inflammatory changes in the TMJ.

PMID- 2003022
TI  - A technique for evaluating bony changes in the anterior edentulous maxilla: a
      modification of a cephalometric analysis.
AB  - A modification of a cephalometric analysis is presented for evaluating maxillary
      bone loss in the edentulous maxilla. The analysis involves tracing a lateral
      cephalometric radiograph of an edentulous maxilla, identifying the new landmarks,
      and measuring the appropriate vertical and horizontal distances of the maxilla.
      Comparison of the measurements for the patient's initial or baseline radiographic
      analysis with those of the patient's follow-up radiographic analysis identifies
      the amount of bone loss that has occurred between the two examinations.

PMID- 2003023
TI  - Shortened roots in the maxilla and mandible.

PMID- 2003024
TI  - Phantom cysts/granulomas after removal of impacted canines.

PMID- 2003025
TI  - Unusual trajectory of a bullet trapped in the temporal area.

PMID- 2003026
TI  - [Trace element deficiency in healthy subjects based on multi-element analysis of
      serum and plasma].
AB  - Among other elements (manganese, molybdenum, cadmium, mercury, lead, nickel), the
      levels of selenium in healthy human sera (n = 56) and plasma (n = 15) were
      measured by ICP spectrometry. It was ascertained by the multielement analysis
      that of 40 nineteen year-old males (from 28 different villages in one county 15
      showed lower than detectable levels of selenium in their sera (n = 25) and plasma
      (n = 15) samples. For this reason, the selenium contents of the sera of 31 blood
      donors were determined by the ICP spectrometry, with hybrid generation. By this
      same technique the selenium in sera of 16 men aged between 24-60 years (mean =
      43.3 years) was measured as 24.06 micrograms/l (13-42 micrograms/l), while in 15
      women between the ages of 19-64 years (mean 39.3 years) it amounted to 20.86
      micrograms/l (11-31 micrograms/l). In 28 cases from 40 samples (25 sera and 15
      plasma) the concentration of molybdenum was smaller than the detectable limit
      (less than 0.0011 mg/l). Firstly, these results prove that amongst healthy
      individuals, in Hungary, molybdenum and selenium deficiency states exist. The
      authors conclude that there is a relationship between these deficiency states, as
      risk factors, and the frequently occurring diseases (malignant tumours,
      cardiovascular diseases, etc.) in Hungary.

PMID- 2003027
TI  - [Sphincter-saving procedure of abdomino-peritoneal amputation? Surgical
      management of cancer of the lower two third of the rectum].
AB  - The authors report their results in surgical treatments of carcinoma localized in
      the low two thirds of the rectum done between 1980 and 1988. The number of
      patients was 150. Resectability: 119/150 = 79.33 per cent. Lethality: 4/119 = 3.3
      per cent. Seventy three of the patients (61 per cent) had sphincter saving
      procedures and 46 of them (38.7 per cent) had abdominoperineal excision. Out of
      the 64 low anterior resection 2 patients (L: 2/64 = 3.1 per cent) and out of the
      46 abdominoperineal excision also 2 patients (L: 2/46 = 4.5 per cent) were lost.
      In the sphincter saving group the distal clearance margin was decreased to below
      3 cms at 29 patients without having local recurrence. CONCLUSION: in many cases
      of the carcinoma localized in the middle third of the rectum (at 82 per cent of
      our own patients) the sphincter can be saved without having more local
      recurrences. Decreasing the distal clearance margin to 2.5 cms does not increase
      the possibility of local recurrence if we do it cranially the same way as at
      Miles operation and remove the mesorectum caudally and laterally.

PMID- 2003028
TI  - [Correlation of HLA antigens and idiopathic hemochromatosis in Hungary].
AB  - The aim of our present work was to collect data on HLA distribution in patients
      with idiopathic haemochromatosis in Hungary. Ten unrelated patients with
      idiopathic haemochromatosis (6 men, 4 women) were studied. Idiopathic
      haemochromatosis was diagnosed on clinical, biochemical and histological grounds.
      HLA typing was performed in 10 probands and in all of their first degree
      relatives available (24) through 7 pedigree studies. HLA A3 was present in 6 of
      10 probands [6/10 vs. 18.8% in the group of healthy blood donors (No 53) and
      22.4% in Hungarian population (No 1910]. HLA B7 was present in 4 of 10 probands
      (40% vs. 11.3% and 14.6%). A3B7 antigen association has been found in 4 of 10
      patients. A3B7 and A2B38 haplotypes were present twice in 4 of 7 genotyped
      probands. Pedigree studies revealed one nonaffected homozygote, 17 heterozygotes
      and 6 non carriers. Extended family and population studies are necessary to
      establish the gene frequency in Hungary and the probability of the involved
      haplotypes other than A3B7.

PMID- 2003029
TI  - [Significance in unilateral intermittent breast stimulation in prenatal
      diagnosis].
AB  - 50 intermittent, unilateral breast stimulation test were studied, which were
      registered not more than 7 days before labour. The authors wanted to know how
      informative this method is to the fetal state, how much time it takes and which
      are the most common side effects. This method was compared with a previously by
      the authors publicated unilateral, continuous breast stimulation test. It is
      concluded that the intermittent, unilateral breast stimulation test well
      indicates the fetal state, though it takes more time, but no hyperstimulation was
      found in this study. The authors suggest to choose this unilateral, breast
      stimulation test as a first step because of its simplicity and shortness and
      cheapness. Only in case of unsuccess the next choice should be the intravenous
      oxytocin challenge test.

PMID- 2003030
TI  - [Successful operation of bleeding perforated Curling's ulcer].
AB  - The Curling's ulcer is a special form of the stress ulcers which occurs in the
      stomach and duodenum in 2.0-25%. It's pathogenesis is unknown even though it is
      clearly related to larger burns poor early treatment and septic complications.
      Since the institution of routine prophylaxis of H2 receptor antagonists and
      antacids have decreased the incidence of Curling's ulcers and have reduced the
      occurrence of clinical complications of ulcers too: the perforation and bleeding.
      In the large patient-number of the author (2300 pro 22 yrs.) the occurrence of
      the Curling's ulcer is 0.82%! In the burn-disease (30-40% of the all burn
      injuries) that is 2.0--2.7%. The author discusses 3 successfully operated
      Curling's ulcer bleeded and perforated.

PMID- 2003031
TI  - [The effect of l6th century Italian Aristotelianism on medicine].

PMID- 2003032
TI  - [Attila Jozsef and Carl Gustav Jung].

PMID- 2003033
TI  - [Urinary N-acetyl-beta-D-glucosaminidase activity in healthy, polycythemic and
      hypoxic newborn infants].
AB  - Urinary N-acetyl-beta-D-glucosaminidase (NAG) activity was assayed in 20
      polycythemic newborns and prematures, together with 50 prematures suffering from
      hypoxia on the 1st, 2nd, 4th, 14th, and 28th day after birth. The enzyme was also
      assayed in 101 healthy newborns which provided normal reference values. NAG
      activity was factored by the creatinine concentration to given an index. There
      were significant difference in the NAG indices either between full-term and
      preterm babies or between appropriate for gestational age (AGA) and small for
      gestational age (SGA) neonates of the normal group. However, NAG excretion on the
      first day of life was significantly raised in the case of polycythemic newborns.
      Following partial plasma exchange, on the 14th day the NAG activity returned to
      the normal range. NAG activities of premature babies suffering from idiopathic
      respiratory distress syndrome (IRDS) were significantly elevated on the 1st, 2nd,
      4th day but fell sharply to the 14th day. NAG activity fell to normal values by
      the 28th day. These results suggest that the urinary NAG index is a sensitive
      indicator of the renal tubular damage during the newborn period.

PMID- 2003034
TI  - [Results of amputation and rehabilitation].
AB  - Authors report on a questionnaire study of amputees having been rehabilitated in
      three departments of the National Institute of Medical Rehabilitation in 1988.
      The study was conducted one and a half years (average) after amputation. In
      comparison to an earlier study on a similar population the ratio of distal
      amputations has increased and the prosthetic fitting has improved. From these
      points results are well comparable with international standards. The feeling of
      isolation of the amputees has decreased since the earlier study. Their chance to
      get a job has deteriorated essentially, their subsistence problems have
      increased.

PMID- 2003035
TI  - [Experience with in vitro rapid diagnostic methods (DHS-CLA) in childhood
      bronchial asthma].
AB  - The authors examined the value of the chemoluminescent assay (CLA) in 35
      asthmatic children. Each serum sample was examined concerning its reaction with
      35 allergen extracts and the appropriate IgE value was also determined. The
      allergen-panel was adapted to the Hungarian prevalence. Results were read within
      24 hours. Skin prick test and in vitro CLA results were in agreement in 89% of
      measurement. Purified, major antigens (grass, mite) gave a specially good
      concordance. Good agreement was also found in highly sensitized patients and
      children in the age below 3 years; in such cases RAST and CLA values were
      compared. In discordant cases revision of anamnesis supported the positive CLA
      result, however in some (5) negative CLA test this could not be strengthened.
      Chemoluminescent assay was shown to be fast, reliable and risk-free method, but
      high costs still limit its general use.

PMID- 2003036
TI  - [Bone substitution using allogenic bone preserved in methiolate].
AB  - Based on their own material authors analyse the results after implantation of
      merthiolate-banked allogenic bone grafts; 327 cases are reviewed grouped
      according to the size of the graft. Based on the radiographic picture the healing
      period was measured in each case. It is stated that no clinical evidence of any
      immunologic reaction was found in this material. The described method can be an
      alternative way of bone grafting in those cases where autotransplantation cannot
      provide the desired amount of bone or its risks are present.

PMID- 2003037
TI  - [Diagnostic and therapeutic problems in a severe case of bacterial contamination
      of the small intestine].
AB  - Five years case record of a 18 year old man is reported. Because of sustained
      diarrhea he was treated several times on departments for infectious diseases. The
      patient was operated on three times in various surgical departments because of
      vigorous abdominal pain, cachexia and CT scan finding. In addition
      extraintestinal complications and symptoms delayed the diagnosis. The diagnosis
      was verified by the H2 breath test and microbiological examination of intestinal
      juice. Complaints of patient ceaset after sustained Ciprobay therapy. The severe
      deficiency symptoms were relieved by complex substitution.

PMID- 2003038
TI  - [A case of choledochal cyst simulating kyphoscoliosis].
AB  - The authors describe a patient's case with choledochus cyst whose leading symptom
      was antalgetic oblique carriage giving rise to the suspicion of kyposcoliosis.
      They briefly survey the etiopatogenesis, diagnosis and therapy of the choledochus
      cyst.

PMID- 2003039
TI  - [The role of oxidative stress, caused by amiodarone, in the side effects of the
      drug].
AB  - It was supposed that free radicals are produced during the metabolism of
      amiodarone and involved in the mechanism of the drug's side effects. In vitro and
      in vivo experiments were performed in rats to check this hypothesis. We verified
      that amiodarone generated free radicals in vitro by chemiluminometric method. The
      light emission induced by amiodarone was inhibited by dihydroquinoline type
      antioxidants CH 402 and MTDQ--DA in a dose dependent manner. The malondialdehyde
      content, --one of the end products of lipid peroxidation--was increased by in
      vivo amiodarone administration in the serum and liver homogenate of rats.
      Amiodarone treatment increased significantly the NADPH and Fe3+ induced lipid
      peroxidation in rat liver microsomal fractions. The protective effect of
      antioxidants, MTDQ--DA and silibinin were ambiguous in these in vivo "short term"
      experiments.

PMID- 2003040
TI  - Ultrastructural ciliary defects in children with recurrent infections of the
      lower respiratory tract.
AB  - One hundred fifty-four children with recurrent or chronic infections of the lower
      respiratory tract compatible with the diagnosis of primary ciliary dyskinesia
      (PCD) were evaluated for the presence of ultrastructural ciliary abnormalities.
      Studies were performed on multiple samples of respiratory mucosa obtained by
      nasal and bronchial brushing. Twenty-eight children showed ultrastructural
      ciliary defects compatible with the diagnosis of PCD: Twenty-four presented
      dynein arm deficiency (either as isolated defect or in association with
      microtubular abnormalities), two had ciliary aplasia, and two showed microtubular
      abnormalities. Eleven patients with PCD had situs viscerum inversus,
      bronchiectasis, and chronic sinusitis (Kartagener's syndrome); one child with
      Kartagener's syndrome had normal ciliary structure. The appearance of respiratory
      symptoms within the first month of life, the colonization by Haemophilus
      influenzae, and a history of recurrent rhinitis and otitis were
      characteristically present in children with PCD. The clinical status of those
      patients who reached adolescence was, in our experience, remarkably good. An
      early diagnosis with adequate prevention and therapy of respiratory infections
      may have an important role in minimizing irreversible lung damage.

PMID- 2003041
TI  - The paradox of adult respiratory distress syndrome in neonates.
AB  - Six full-term newborn infants are described who suffered from severe adult
      respiratory distress syndrome (ARDS). The triggering event was
      intrauterine/perinatal asphyxia in five, and group B streptococcal (GBS)
      septicemia in three. All had severe respiratory distress/failure and were
      ventilated mechanically with high concentrations of inspired oxygen and positive
      end-expiratory pressure. Radiography of the chest showed dense bilateral
      consolidation with air bronchograms and reduced lung volume. Persistent pulmonary
      hypertension (PPH) was documented in all cases. The coincidence of ARDS and PPH
      rendered respiratory management extremely difficult. For this reason high
      frequency ventilation was instituted in all patients in order to improve CO2
      elimination and induce respiratory alkalosis. Acute complications of respiratory
      therapy were encountered in five patients (pneumothorax, pulmonary interstitial
      emphysema, pneumopericardium). Three infants died (irreversible septic shock,
      progressive severe hypoxemia, and sudden cardiac arrest) after 17, 80, and 175 h
      of life. Histologic examination of the lungs was possible in all fatal cases and
      revealed typical changes of acute to subacute stages of ARDS. Three infants
      survived, the mean time of mechanical respiratory support being 703 h. Two
      patients were still dependent on oxygen after 1 month of life, and all survivors
      had increased interstitial markings and increased lung volumes on their chest
      roentgenograms at this time.

PMID- 2003042
TI  - Effect of inhaled beclomethasone dipropionate on bronchial hyperreactivity in
      asthmatic children during maximal allergen exposure.
AB  - In this double blind study we evaluated the effect of a 2 months long treatment
      with inhaled beclomethasone dipropionate (300 micrograms/day) on methacholine
      responses in asthmatic children, during a period of maximal allergen exposure.
      Baseline values of methacholine PC20-FEV1 were 0.66 +/- 0.22 mg/mL (mean +/- SEM)
      in 10 children treated with the active drug and 0.78 +/- 0.21 mg/mL in 10
      children treated with placebo. After 1 month of treatment PC20-FEV1 was 1.91 +/-
      0.64 and 0.80 +/- 0.33 mg/mL, respectively, in the groups treated with
      beclomethasone versus placebo. A statistically significant reduction in bronchial
      hyperreactivity (PC20-FEV1, 5.49 +/- 1.86 mg/mL) but no systemic side effects
      were observed after 2 months of treatment with beclomethasone dipropionate. This
      is compared with a PC20-FEV1 of 1.38 +/- 0.52 mg/mL in the placebo group. The
      results confirm the effect of inhaled corticosteroids in reducing bronchial
      hyperreactivity, even during a period of maximal allergen exposure.

PMID- 2003043
TI  - Digital clubbing and pulmonary function abnormalities in children with lung
      disease.
AB  - Digital clubbing and pulmonary function tests were measured in children,
      adolescents, and adults with chronic lung diseases to determine pulmonary
      function correlates with a quantitative measure of clubbing. The group had a mean
      age of 13.8 +/- 6.0 (SD) years, mean PaO2 of 81 +/- 21 mm Hg, and mean FEV1 of
      60% +/- 26% predicted. Digital clubbing was diagnosed in 43 cases when the distal
      phalangeal depth to interphalangeal depth (DPD/IPD) ratio, measured on a finger
      cast, was greater than or equal to 1 (greater than 3 SD above mean from 85
      controls; no history of pulmonary disease; mean age, 14.8 +/- 7.6). The PaO2 of
      patients with digital clubbing was 69.4 +/- 2.1 (SEM) mm Hg compared with 88.3 +/
      1.3 mm Hg in those without digital clubbing (P less than 0.0001). Digital
      clubbing was present in 39 of the 84 (46%) hypoxic patients (PaO2 less than or
      equal to 88) but only four of the 78 (5%) normoxic patients (P less than 0.0001).
      The DPD/IPD ratio was negatively correlated with PaO2 in subjects with cystic
      fibrosis and interstitial fibrosis. Weak negative correlations were seen for all
      other subjects except asthmatics. Overall, the DPD/IPD ratio was significantly
      correlated with PaO2 (r = -0.53; P less than 0.0001). The DPD/IPD ratio was
      correlated with other lung function abnormalities (increased RV, decreased FEV1,
      and FEF25%-75%) only for the subjects with cystic fibrosis. We conclude that
      digital clubbing is associated with hypoxemia and airway obstruction. The
      relation is seen most clearly in subjects with cystic fibrosis, possibly
      reflecting the prolonged duration of hypoxemia. Digital clubbing is rarely seen
      in normoxic subjects.

PMID- 2003044
TI  - Do wheezy infants recovering from bronchiolitis respond to inhaled salbutamol?
AB  - Wheezy infants, less than 6 months of age, were given either inhaled salbutamol
      or saline in a double-blind study. A significant change in maximal flow at
      functional residual capacity (VmaxFRC) was defined as being greater than twice
      the coefficient of variation of the baseline measurements. There was no
      difference in the infants' response to saline or salbutamol. Wheezy infants, less
      than 6 months of age, do not have an increase in VmaxFRC following a single dose
      of inhaled salbutamol.

PMID- 2003045
TI  - The effect of triclofos sodium sedation on respiratory rate, oxygen saturation,
      and heart rate in infants and young children.
AB  - Chloral hydrate is frequently used to sedate infants for lung function testing.
      While no effect on respiratory function has been demonstrated, a recent study has
      reported a fall in oxygen saturation (SaO2) following sedation in wheezy infants.
      This study was designed to assess the effects of the closely related but less
      gastrically irritant drug triclofos sodium on respiratory rate (RR), heart rate
      (HR), and SaO2 in infants without cardiopulmonary disease. Paired measurements
      using respiratory inductance plethysmography and pulse oximetry were obtained in
      10 infants (4-19 months of age) during natural and sedated sleep. Following
      sedation with triclofos, mean RR rose by 1.9 breaths min-1 (95% confidence
      intervals [Cl] of the mean difference: 0.13-3.7 min-1). Mean heart rate rose by
      5.5 beats min-1 (95% Cl: -0.9-11.9 min-1). Mean SaO2 fell by 0.68% (95% Cl -1.8
      0.45%). None of these changes are considered to be of clinical importance, and
      only the change in RR reached statistical significance at the 5% level.

PMID- 2003046
TI  - Effect of infant position on breath amplitude measured by transthoracic impedance
      and strain gauges.
AB  - Continuous monitoring of respiration by transthoracic electrical impedance gives
      a signal that has certain not well understood irregularities. Among them is a
      change in the amplitude of the signal when there is no apparent change in the
      infant's tidal respiration. One factor that could hypothetically account for
      alterations of the impedance signal is a change in current path through the
      thorax secondary to a change in body position. To test this hypothesis we have
      studied the relationships between breath amplitude measured by transthoracic
      impedance, one strain gauge on the chest and one on the abdomen, and tidal volume
      by integrated flow in four body positions. Median breath amplitude was found to
      vary significantly with body position according to the measuring device. The
      median impedance breath amplitude increased by 27% in the supine position
      compared with the prone position, with no associated change in tidal volume.
      Differences in the strain gauge signal amplitude for these positions were not
      statistically significant. Correlation between breath amplitude measured by
      impedance changes and tidal volume was minimal (r = 0.114). These results
      indicate that infant position affects impedance breath amplitude independently of
      changes in tidal volume.

PMID- 2003047
TI  - Progressive pulmonary lymphangiectasia.

PMID- 2003048
TI  - Analysis of expiratory pattern for monitoring bronchial obstruction in school-age
      children.
AB  - This study was designed to assess the validity of the percent of volume expired
      at tidal peak flow (dV/Vt) as an indicator of bronchial obstruction in school-age
      children. We analyzed 126 dV/Vt ratios and compared them with spirometric and
      plethysmographic results measured in 24 healthy (14 males) and 60 asthmatic (41
      males) children; 42 of them underwent measurements before and after bronchial
      challenge with histamine. The two groups differed in resistance, forced
      expiratory volume in 1 sec (FEV1), and forced expiratory flows, as percents of
      predicted (FEV1: 94.6 +/- 2.4% in controls vs 86.7 +/- 1.6% in asthmatics; P less
      than 0.001). They did not differ in peak expiratory flow (PEF), forced vital
      capacity, functional residual capacity, measured by body plethysmography, and in
      dV/Vt. The dV/Vt was found to correlate with FEV1 (r = 0.58, P less than 0.001),
      PEF (r = 0.57, P less than 0.001), and other lung function parameters. Forty-two
      of the asthmatic children performed a bronchoprovocation histamine test. The fall
      of dV/Vt after histamine was significantly correlated (r = 0.61, P less than
      0.001) with the variation in FEV1 and other lung function parameters. We conclude
      that dV/Vt is a good indicator of bronchial obstruction, as useful in school-age
      children as in adults and infants, with no need for the subject's cooperation.

PMID- 2003050
TI  - The American Pediatric Society and the Society for Pediatric Research. April 29
      May 2, 1991, New Orleans, LA. Abstracts and program outline.

PMID- 2003049
TI  - On the effect of the thermodynamics of an infant plethysmograph on the
      measurement of thoracic gas volume.

PMID- 2003051
TI  - Evaluation of ventilating tubes and myringotomy in the treatment of recurrent or
      persistent otitis media.
AB  - In a prospective controlled study of the efficacy and sequelae of ventilating
      tubes, 44 children with bilateral recurrent acute otitis media (greater than 6
      episodes/year) and 13 children with bilateral persistent middle ear effusion
      (greater than 3 months) received unilateral ventilating tube insertion in a
      randomly selected ear. The contralateral ears were randomized to receive either
      myringotomy alone or no surgery. Clinical, otoscopic, tympanometric and
      audiologic examinations were performed before the study and 2 to 4 weeks later,
      then at 3-month intervals for up to 2 years and at 36 months after surgical
      randomization. Medical therapy and antibiotic prophylaxis were used whenever
      indicated. While the ventilating tubes remained functional (mean duration, 10
      months) the ears with a tube had significantly fewer episodes of otitis media
      than their contralateral ear (P less than 0.001; 95% confidence intervals -0.7, 
      1.7) and had more hearing improvement (P = 0.005; 95% confidence intervals, -5.9,
      -1.2). After tube extrusion there was a tendency for surgically treated ears to
      have more otitis and worse hearing, but not at a significant level.
      Tympanosclerosis, retraction and atrophy were more common in ears that received
      tubes. The majority of ears treated medically also improved. There is need for a
      more cautious and selective use of ventilating tubes.

PMID- 2003052
TI  - Evidence of infection with organisms producing Shiga-like toxins in household
      contacts of children with the hemolytic uremic syndrome.
AB  - We conducted a prospective study in 87 household contacts of 51 children with
      hemolytic uremic syndrome to determine the frequency of infection with Shiga-like
      toxin-producing bacteria. Gastrointestinal tract symptoms occurred in only 1 of
      87 contacts. Free fecal toxin was detected in 25 of 64 (39%) of the household
      members. Neutralization with specific antisera to Shiga-like toxins I and II (SLT
      I, SLT-II) revealed that in 6 of these household contacts only SLT-I was present
      in stool, in 10 only SLT-II was present and in 9 both toxins were found. Thirty
      three percent of the hemolytic uremic syndrome families in which 2 or more
      members were studied had more than 1 household member with free fecal toxin in
      stool. None of the household contacts was found to have E. coli O157:H7 in feces.
      Serum samples were available in 77 household contacts; 75% (58 of 77) had serum
      neutralizing titers of greater than or equal to 1:4 to 1 or both toxins. In those
      contacts for whom paired sera were available, seroconversion was found in 10 of
      24 (42%). These data show that household contacts of children with hemolytic
      uremic syndrome are commonly colonized with Shiga-like toxin-producing E. coli
      and seroconversion to Shiga-like toxins occurs frequently in family members of
      children with hemolytic uremic syndrome.

PMID- 2003053
TI  - Antimicrobial drug suspensions: a blind comparison of taste of fourteen common
      pediatric drugs.
AB  - Children of preschool age most often receive medications in liquid form, and
      smell and taste are major determinants in achieving compliance. We compared
      smell, taste and other characteristics of 14 commonly prescribed antimicrobial
      suspensions in a blind test in 30 adult volunteers to determine whether there was
      a difference in their acceptability. A significant difference was observed with
      cephalosporins ranking highest and penicillins ranking lowest. Our findings
      support anecdotal observations and claims often made by parents that
      cephalosporin antimicrobial suspensions taste good and are readily accepted by
      children and that penicillin suspensions have an unpleasant taste and aftertaste
      and are poorly accepted. Other drugs had intermediate scores. Of the two
      erythromycin suspensions evaluated, Ilosone tested superior to Erythromycin ES.

PMID- 2003054
TI  - Etiology of acute lower respiratory tract infections in Gambian children: II.
      Acute lower respiratory tract infection in children ages one to nine years
      presenting at the hospital.
AB  - Seventy-four children ages 1 to 9 years hospitalized because of severe pneumonia
      were investigated using blood cultures, lung aspirates, nasopharyngeal aspirates,
      serology and antigen detection procedures. A bacterial infection was identified
      in 57 (77%), a viral infection was seen in 25 (34%) and 18 (24%) had mixed viral
      bacterial infections. The bacterial pathogens most frequently identified were
      Streptococcus pneumoniae and Haemophilus influenzae found in 61 and 15% of
      patients, respectively. The viral pathogen most frequently recovered was
      respiratory syncytial virus (12%). Evidence of Chlamydia pneumoniae strain TWAR
      and Mycoplasma pneumoniae infection was found in 12 and 4% of cases,
      respectively. Overall a potential pathogen was identified in 60 (81%) children,
      with evidence of polymicrobial infection in 30 cases (40.5%). The study provides
      information on the relative role of different infectious agents in the etiology
      of severe pneumonia in children in a developing country.

PMID- 2003055
TI  - Tinea capitis.

PMID- 2003056
TI  - Transfusion and coagulation factor-acquired human immunodeficiency virus
      infection.

PMID- 2003057
TI  - Coagulase-negative staphylococcal infections in neonates.

PMID- 2003058
TI  - Subacute sclerosing panencephalitis.

PMID- 2003059
TI  - Acute uvulitis apparently caused by Candida albicans.

PMID- 2003060
TI  - Community-acquired Flavobacterium meningosepticum meningitis, pneumonia and
      septicemia in a normal infant.

PMID- 2003061
TI  - Cryptococcus infection in a nine-year-old child with hemophilia and the acquired
      immunodeficiency syndrome.

PMID- 2003062
TI  - Streptococcal toxic shock-like syndrome as a complication of varicella.

PMID- 2003063
TI  - Zosteriform denuded skin caused by intrauterine herpes simplex virus infection.

PMID- 2003064
TI  - Your diagnosis, please. Fever of unknown origin in a five-year-old boy.

PMID- 2003065
TI  - DNA probes in sexual abuse.

PMID- 2003066
TI  - Reactions to ribavirin.

PMID- 2003067
TI  - The risk of dexamethasone in pregnant women with a history of recurrent genital
      herpes.

PMID- 2003068
TI  - Prevalence of cigarette smoking in Hispanic women of childbearing age.
AB  - A secondary analysis of Hispanic Health and Nutrition Examination Survey data was
      conducted to determine the prevalence and degree of cigarette smoking among large
      probability samples of Cuban-American, Mexican-American, and Puerto Rican women
      of childbearing age. Percentages, means, and 95% confidence intervals were used
      to determine age-adjusted and age-specific rates for each Hispanic group. Age
      adjusted smoking prevalence rates were 23.2%, 22.6%, and 33.5% for Mexican
      Americans, Cuban-Americans, and Puerto Ricans, respectively. Age-specific rates
      indicated that all Puerto Rican women under the age of 40, Mexican-American women
      in their 40's, and Cuban-American women in their 30's had smoking prevalences
      higher than the national average for women. Although most Hispanic women were
      relatively light smokers, prevention and cessation interventions need to be
      developed for Puerto Rican women of childbearing age who demonstrated high
      smoking prevalences.

PMID- 2003069
TI  - Reliability and validity of the work assessment scale for persons with multiple
      sclerosis.
AB  - Reliability and validity of the Work Assessment Scale (WAS) was done on a sample
      of 551 subjects with multiple sclerosis. Work was defined as those activities
      performed in employment, homemaking and/or personal care. The WAS has two parts
      consisting of: Work-Impeding (WAS-I) and Work Enhancing (WAS-E) situations and
      conditions. Varimax rotated factor analysis of the WAS-I resulted in a seven
      factor solution containing 33 of the 53 scale items. Theta reliability
      coefficients for the factors ranged between .73 and .90 and test-retest
      correlation coefficients (n = 51) ranged between .76 and .91. Varimax rotated
      factor analysis of the WAS-E resulted in a five-factor solution containing 19 of
      the 27 scale items. Theta reliability coefficients for the factors ranged between
      .66 and .81 and test-retest correlation coefficients ranged between .68 and .82.
      Concurrent validity was shown between WAS and both ADL and Symptom subscales.

PMID- 2003070
TI  - A summary of findings of a five-year comparison study of primary and team
      nursing.
AB  - This study compared primary and team nursing in three areas: quality of care,
      impact on nursing staff, and cost. Eight medical units in one hospital were
      evaluated. The study was conducted over a four-year period utilizing three
      phases: one preintervention phase and two postintervention phases. The study used
      multiple measures including two approaches to analysis of cost. The findings of
      this study confirm that primary nursing does result in a higher quality of
      nursing care than team nursing and that nurse retention is improved in primary
      nursing. In addition, this study shows that, both directly and indirectly,
      primary nursing reduces costs when compared to team nursing.

PMID- 2003071
TI  - Homeostasis conservation among undergraduate nursing students.

PMID- 2003072
TI  - Approaches to qualitative-quantitative methodological triangulation.

PMID- 2003073
TI  - The death of Sadie Sachs.

PMID- 2003075
TI  - The missing puzzle piece.

PMID- 2003074
TI  - Re: 'Adolescent reactions to sibling death: perceptions of mothers, fathers, and
      teenagers'.

PMID- 2003076
TI  - A review of the literature on cocaine abuse in pregnancy.
AB  - The primary research literature on cocaine abuse in pregnancy from 1982 to 1989
      was reviewed. This article is a synthesis of current knowledge regarding the
      effects of maternal cocaine use during pregnancy on obstetrical, neonatal, and
      infant health and developmental outcomes. Consistencies and inconsistencies in
      the findings, a critique of key methodological issues, and suggestions for future
      research are provided.

PMID- 2003078
TI  - The sensation of pulmonary dyspnea in school-age children.
AB  - The purpose of this investigation was to describe the sensation of dyspnea in a
      sample of 39 school-age children with asthma and to identify strategies used to
      cope with the symptom. In addition, three methods to measure dyspnea intensity in
      children were tested and compared. Breathing on a "bad breathing day" was used as
      a proxy variable to represent dyspnea. The most frequent description of how
      breathing feels on a bad day was "it is hard to breathe." Words chosen most
      frequently from a checklist of sensations were "wheezy," "short of breath,"
      "tight," and physical sensations such as "throwing up," "hurting," and
      "stuffiness." The children's feelings on a bad breathing day were categorized as
      negative moods or emotions, a wish for change, or physical symptoms. Ratings of
      breathing on "good", "bad," and "usual breathing" days on word descriptor, visual
      analogue, and color scales provided evidence of concurrent validity for the three
      measures of dyspnea intensity. The most frequent strategies used to cope with
      dyspnea were medications, change in position, decreased activity, fluids,
      relaxation, distraction, and social support. The findings were very similar to
      those previously described for an adult sample.

PMID- 2003077
TI  - The effect of lung hyperinflation and endotracheal suctioning on cardiopulmonary
      hemodynamics.
AB  - The purpose of this study was to examine the effect of sequential lung
      hyperinflation breaths followed by suction on mean arterial pressure (MAP),
      cardiac output (CO), pulmonary artery pressure (PAP), and pulmonary airway
      pressure (Paw) to elucidate the mechanism for the increase in MAP seen with lung
      hyperinflation and suction. Thirty-four postoperative coronary artery bypass
      graft patients were randomly exposed to three lung hyperinflation breaths at one
      of five volumes (tidal volume, 12cc/kg, 14cc/kg, 16cc/kg, and 18cc/kg of lean
      body weight) using a ventilator followed by 10 s of suctioning repeated for a
      total of three times. There was a mean increase in MAP (13.71 torr), CO (12.2%),
      PAP (4 torr), and Paw (23.5 torr) above baseline over the three sequences. The
      mechanism for the increase in MAP with lung hyperinflation may be attributed to
      transient increases in intrathoracic pressure, resulting in increased left
      ventricular preload and CO.

PMID- 2003079
TI  - An evaluation of three blood pressure methods in a stabilized acute trauma
      population.
AB  - Blood pressure values were evaluated in 30 acute adult trauma patients using two
      indirect methods, the bell and diaphragm components of the stethoscope, and one
      direct arterial method. K1, K4, and K5 measurements were taken 4 to 72 hours (M =
      30) after admission when vital signs had stabilized. Data were collected using a
      random-zero (RZ) sphygmomanometer for indirect blood pressure and radial
      intraarterial cannula for direct blood pressure. The sequence of measurement was
      randomized and variables shown to alter blood pressure values were controlled.
      There was no overall significant difference in K1, K4, and K5 blood pressures
      among the three methods. These results suggest that when clinicians monitor
      variables such as the frequency response of arterial lines and peripheral
      vascular resistance, indirect blood pressure methods are reliable for use with
      stabilized trauma patients.

PMID- 2003080
TI  - Comparison of tympanic and oral temperatures in surgical patients.
AB  - The purpose of this study was to compare tympanic and oral temperatures at four
      times during the perioperative period in 60 adults having major abdominal
      surgery. Tympanic temperature was measured with an infrared thermometer and oral
      temperature with a predictive thermistor thermometer. Measurements at the two
      sites were similar in pattern and moderately well correlated. Tympanic
      temperature was somewhat more sensitive to the effects of an intervention
      influencing body temperature. The tympanic-oral temperature offset was relatively
      stable over time, with tympanic readings having a smaller range of values at each
      measurement. Tympanic temperature measurement variation was fairly small, with
      92% of readings reproducible within 0.5 degree F (0.3 degree C); comparable oral
      data were not available. The findings suggest that the tympanic site offers some
      advantage, but that either tympanic or oral readings would be satisfactory for
      routine intermittent monitoring of body temperature during the perioperative
      period.

PMID- 2003081
TI  - Serial neurobehavioral assessments in preterm infants.
AB  - The purpose of this study was to compare serial neurobehavioral assessments in a
      sample of preterm infants with intraventricular hemorrhage (IVH) to those of a
      group of unaffected preterm infants. Of the 30 infants included in the study, 5
      infants had a grade III or IV/VI intraventricular hemorrhage. Infants with IVH
      demonstrated more abnormalities in mental status and a cluster of abnormal
      neurologic findings (persistent ankle clonus, tremulousness, and brisk deep
      tendon reflexes). Of the 30 infants, 20 infants were included in a brain
      metabolism study. Infants who had experienced an IVH had significantly different
      brain metabolism findings, as measured by nuclear magnetic resonance spectroscopy
      (NMR). There was a significant correlation between one measure of brain
      metabolism (PCr/PI) and the neurobehavioral assessment rating for infants with
      IVH.

PMID- 2003082
TI  - The emergence of body temperature biorhythm in preterm infants.
AB  - The biorhythm of body temperature was studied in five hospitalized, medically
      stable preterm infants, gestational age 30 to 34 weeks and postnatal age 5 to 10
      days. Abdominal skin temperature, as well as incubator air temperature, were
      measured by thermistors and recorded at one-minute intervals throughout a 24-hour
      day using a computerized data acquisition system. Data were analyzed using
      autocorrelation, a form of time series analysis. A cyclic pattern of temperature
      was observed in three of the five subjects. The length of time of the cycles were
      two, three, and six hours. Incubator air temperature did not exhibit similar
      cyclicity, and it is therefore assumed that incubator operation is not
      responsible for the observed cyclic variation in infant temperature.

PMID- 2003083
TI  - After the fallout.

PMID- 2003084
TI  - Ulster upset.

PMID- 2003085
TI  - Ring of confidence.

PMID- 2003086
TI  - Advance warning.

PMID- 2003087
TI  - Working with doctors. Uneasy partnership.

PMID- 2003088
TI  - Working with doctors. Educational conditioning.

PMID- 2003089
TI  - April fools.

PMID- 2003090
TI  - Midwifery. The price of motherhood.

PMID- 2003091
TI  - Making sense of ... laryngeal masks.

PMID- 2003092
TI  - Races apart?

PMID- 2003093
TI  - Assessor evaluation of quality assurance.

PMID- 2003094
TI  - Home treatment for acute psychiatric illness.

PMID- 2003095
TI  - Handicaps associated with incontinence.

PMID- 2003096
TI  - Scenting relief.

PMID- 2003097
TI  - Nurse education. What future for the boards?

PMID- 2003098
TI  - Nurse education. How to organise ... microteaching.

PMID- 2003099
TI  - Catheters. Using bladder syringes sparingly.

PMID- 2003100
TI  - Catheters. Preventive procedures.

PMID- 2003101
TI  - Unit for AIDS families to open next year.

PMID- 2003102
TI  - Oncology Knowledge Inventory for undergraduate students.
AB  - A Knowledge Inventory was developed and used to measure undergraduate students'
      knowledge level of oncology nursing. Initial items were written by clinical
      experts, and content was validated by faculty. Pretesting of test items resulted
      in a final scale of 30 items. To further test items for difficulty and
      discrimination, students were asked to complete the Knowledge Inventory each
      semester of the program over a period of three semesters. Results indicated that
      the scale provides a short, general measure of oncology knowledge that
      differentiates student knowledge levels and experience.

PMID- 2003103
TI  - Myelodysplastic syndromes: a review for nurses.
AB  - The Myelodysplastic Syndromes (MDS) are a group of hematologic disorders that
      resemble hematologic malignancies but are often treated much differently. These
      syndromes result from a clonal disorder of certain stem cells in the bone marrow.
      Treatment can range from simple supportive care to new and innovative approaches
      such as immunotherapy. In general, treatment is dictated by the severity of the
      presenting disease. Oncology nurses, because of their familiarity with the
      manifestations of cancer, are particularly qualified to intervene for the patient
      and family experiencing MDS. Nursing interventions, based on a firm understanding
      of the underlying disease, include patients and family education. In addition,
      emotional support and symptom management are important nursing roles.

PMID- 2003104
TI  - Needs assessment and resource identification.
AB  - Given the constraints of the current healthcare system, the mandate for patient
      education is clear - a time-efficient and cost-effective approach. This article
      explores the concept of conducting a needs assessment as a means of clearly and
      efficiently delineating learning needs and learner characteristics. Tools for
      collecting and documenting pertinent patient data should be used to consolidate
      information and should be accessible to all members of the healthcare team,
      avoiding costly duplication of effort. Other valuable resources include patient
      education exchange groups, which can be composed of representatives from all
      interested healthcare organizations in a designated area, and the identification
      and use of free or low-cost teaching tools.

PMID- 2003105
TI  - A nursing data base for initial patient assessment.
AB  - The introduction of nursing diagnoses at Saddleback Memorial Medical Center,
      Laguna Hills, CA, resulted in the nursing process becoming the basis for the
      documentation system. However, the medical model or body system remained the
      organizational structure for nursing data collection and narrative charting. The
      need for a model that would aid in identification and treatment of illness and
      not negatively affect the nursing process was the impetus behind the selection of
      Gordon's functional health patterns as the assessment format. These patterns
      provide a standard method for data collection and a holistic approach to
      assessment and diagnosis.

PMID- 2003106
TI  - Using Montgomery straps to secure dressings.

PMID- 2003107
TI  - The use of Vigilon primary wound dressing in the treatment of radiation
      dermatitis.

PMID- 2003108
TI  - Cornstarch as a treatment for dry desquamation.

PMID- 2003109
TI  - Eliminating odors associated with necrotic lesions.

PMID- 2003110
TI  - Povidone-iodine: potential adverse reactions.

PMID- 2003111
TI  - Care of malignant cutaneous lesions.

PMID- 2003113
TI  - Skin tears: what can you do?

PMID- 2003112
TI  - Managing skin breakdown complicated by candida infection.

PMID- 2003114
TI  - A survey of the role, benefits, and realities of the office-based oncology nurse.
AB  - The office-based oncology nurse plays an increasingly significant role in the
      treatment of patients with cancer as the focus of health care shifts from the
      inpatient to the outpatient arena. Yet the role of the office-based oncology
      nurse is seldom addressed. In 1989, a survey was undertaken to examine the range
      of tasks involved in, the expectations and disappointments associated with, and
      the resulting job satisfaction from the role. A random sample of self-identified,
      office-based oncology nurses received the survey. A total of 192 nurses
      responded; 87% of the respondents indicated a high level of job satisfaction.
      Salary analysis showed wages to be comparable to those paid to inpatient oncology
      nurses. The opportunity to work with patients throughout the phases of disease
      was identified as the most gratifying aspect of the respondents' jobs. The
      opportunity for better work hours and more professional independence were
      frequently cited benefits. The survey's results reveal the evolution of the
      office-based oncology nurse's role into one of a multifaceted, independent
      practitioner.

PMID- 2003115
TI  - Changing the role of the nurse in the hematology-oncology outpatient setting.
AB  - Changing healthcare economics, advances in technology, and consumer preferences
      have escalated the growth of outpatient hematology-oncology services and expanded
      the scope of professional decision making. Currently, 80%-90% of cancer care is
      delivered in the outpatient setting. Moreover, third-party payers are encouraging
      an even greater frequency of out-of-hospital hematology-oncology services.
      Oncology nurses are in key positions to change the outpatient healthcare setting
      in ways that promote quality care and improved use of professional nursing
      knowledge and expertise. This article describes a nurse manager's use of Lewinian
      theory to develop and implement plans for needed change in an outpatient
      Hematology-Oncology Department.

PMID- 2003116
TI  - Bladder preserving combined modality therapy for invasive bladder cancer.
AB  - The purpose of this paper is to increase the nurse's knowledge about invasive
      bladder cancer through discussion of a current protocol treatment using chemo and
      radiation therapy. Pathophysiology, clinical features, and current medical
      management are addressed along with appropriate nursing interventions, including
      symptom management and patient/family education. Research supports the
      observation that once patients complete the protocol regimen, the complete
      response rate is high and the need for radical surgery is low.

PMID- 2003117
TI  - S phase index and ploidy prognostic markers in node negative breast cancer:
      information for nurses.
AB  - The National Cancer Institute (NCI) issued a Clinical Alert on node negative
      breast cancer in May 1988. Based on findings of clinical studies, the Alert
      advised that adjuvant hormonal or cytotoxic chemotherapy could have a meaningful
      impact on the natural history of patients with node negative breast cancer. Prior
      to the Alert, the majority of women diagnosed with node negative breast cancer
      did not receive adjuvant treatment. To determine which patients with node
      negative breast cancer can potentially benefit from adjuvant treatment, a number
      of biological variables need to be considered: menopausal status, tumor size,
      histopathology, nuclear grade, and steroid hormone receptor status. Recently two
      new prognostic indicators--S phase index (SPI) and ploidy--have been incorporated
      into the clinical setting. This article explains these indicators and provides
      patient education information.

PMID- 2003118
TI  - The development and implementation of standards of care in a breast cancer
      screening program.
AB  - The development and implementation of process, structure, and outcome standards
      were an integral part of program development for a mobile mammography screening
      program that provides service for the economically disadvantaged through the
      collaborative effort of eight primary healthcare centers, the Dade County Health
      Department, and the University of Miami/Jackson Memorial Hospital. The standards
      are used to guide and evaluate the screening program's operation and to provide
      the framework for additional program components (e.g., developing performance
      appraisals and quality assurance and risk management programs, establishing
      policies and procedures, and serving as the foundation for education and research
      projects). Examples of standards are provided to assist others in developing a
      systematic and ongoing evaluation plan for mobile mammography screening.

PMID- 2003119
TI  - Breast cancer: demands of illness.
AB  - This study explores the qualitative experience of illness demands from the
      woman's own perspective by asking, "What is the impact of breast cancer on the
      daily lives of women of childbearing age?" Semistructured interviews with 79
      women newly diagnosed with breast cancer were transcribed and analyzed to discern
      illness demands. Content analysis yielded 14 domains of illness demands:
      treatment issues, change in life context or perspective, acceptance of the
      illness, social interaction or support, physical changes, reconstructing the
      self, uncertainty, loss, making comparisons, acquiring new knowledge, making
      choices, mortality issues, financial or occupational concerns, and making a
      contribution. Illness demands are experienced in every aspect of a woman's life,
      including her identity, daily routines, family and social experience, and her
      perception of the past, present, and future. This study details in the women's
      own language the considerable adjustments brought on by a diagnosis of breast
      cancer.

PMID- 2003120
TI  - Correlates of fatigue in people with breast or lung cancer.
AB  - Fatigue is regarded as a universal and unavoidable side effect of cancer therapy,
      yet its epidemiology and prevalence in populations of people with cancer have not
      been well-documented. Using the conceptual framework of Piper, et al., this study
      examined and described the perception and manifestations of fatigue and its
      physiological, biochemical, and behavioral correlates. A convenience sample (N =
      77) of people with lung (n = 33) or breast cancer (n = 44) completed several
      instruments: a brief questionnaire, the Rhoten Fatigue Scale, a visual analogue
      scale (VAS), the Rhoten Fatigue Checklist, and the shortened version of the
      Profile of Mood States (POMS). Data on other factors thought to influence fatigue
      were collected via medical record audit. Seventy-five of 76 people (99%)
      completing the VAS experienced some level of fatigue. Significant correlates of
      fatigue included level of pain and POMS scores. Preliminary findings suggest that
      fatigue is a common problem with a complex etiology and that nurses must consider
      potential contributing factors when assessing fatigue and its impact on the
      individual.

PMID- 2003121
TI  - Public attitudes about health care and nurses.

PMID- 2003122
TI  - Smoking among women: a life cycle perspective on which to base
      prevention/cessation interventions.
AB  - Smoking among women continues at high rates despite the severe health
      consequences that may result for these women and for their children. A conceptual
      model identifying core factors that influence the onset and development of
      smoking and its cessation and continued abstinence was developed and provides a
      framework for understanding women's smoking behavior. This model examines a
      number of smoking-related health consequences that occur during the woman's life
      cycle and proposes suggestions for assessment and nursing intervention.

PMID- 2003123
TI  - Interphotoreceptor retinoid-binding protein: biochemistry and molecular biology.
AB  - Interphotoreceptor retinoid-binding protein (IRBP) is a recent and still somewhat
      enigmatic newcomer in the family of photoreceptor-specific proteins involved in
      vision. It has been isolated, characterized, cloned and sequenced from several
      species in less than a decade. Its extracellular localization and the increased
      amount of bound all-trans retinol following illumination are consistent with the
      proposed function of IRBP in extracellular transport or buffering of retinol and
      retinal isomers in the IPM. Its capacity to bind a great many other hydrophobic
      ligands, however, may indicate a multi-purpose function. Many questions
      concerning biosynthesis and processing, secretion, tertiary structure and ligand
      binding remain to be answered. Perhaps most interesting, from a molecular biology
      point of view, will be the regulation of transcription and tissue-specific
      expression of this photoreceptor protein, and possible involvement of its gene in
      human retinal degenerations. Constructs consisting of IRBP regulatory sequences
      and foreign antigens incorporated into the germ line of transgenic mice will help
      in the characterization of promoters and enhancer elements, while suppression of
      IRBP gene expression and its consequences may give us a more precise answer about
      IRBP function.

PMID- 2003124
TI  - The molecular biology of IRBP: application to problems of uveitis, protein
      chemistry, and evolution.
AB  - In closing, molecular biology has helped us in the study of uveitis, in defining
      the parts of the IRBP molecule that cause EAU/EAP. Simple northern and Southern
      blotting experiments can answer significant questions in the study of gene
      structure and expression and in relating these to genetic eye diseases. Molecular
      biology has provided answers to several long-standing cell biology question such
      as: where is IRBP synthesized, where is the gene expressed, and how is the IRBP
      polypeptide processed? In considering how mother nature invented the IRBP gene,
      the gene structure suggests some interesting alternative models, and causes us to
      speculate about how large proteins may have evolved. Finally, the determination
      of the protein sequence helps to put us in the position to ask and answer
      questions about the function of IRBP. It also allows us to begin to determine the
      consequences of a nonfunctional IRBP. We don't know the answers to all these
      questions yet, but the structural analyses and the isolation of these genes and
      cDNAs, presented here, united with other powerful biological techniques should
      provide the answers.

PMID- 2003125
TI  - S-antigen: molecular mimicry may play a role in autoimmune uveitis.

PMID- 2003126
TI  - Diverse mutations lead to inactivation of the retinoblastoma gene.

PMID- 2003127
TI  - Costumed figures may produce iatrogenic symptoms in delirious patients.

PMID- 2003128
TI  - Enema abuse as a clinical feature of bulimia nervosa.

PMID- 2003129
TI  - Fluoxetine for obsessive fear of loss of control of malodorous flatulence.

PMID- 2003130
TI  - Concerns and issues of the diagnostic category of organic mental disorders in the
      DSM-IV.

PMID- 2003131
TI  - Liver transplantation for the alcoholic patient.

PMID- 2003132
TI  - Exacerbation of mental illness by dental disease.

PMID- 2003133
TI  - On "Consultation-liaison in child psychiatry and the evolution of pediatric
      psychiatry".

PMID- 2003134
TI  - Psychological factors affecting pulmonary and rheumatologic diseases. A review.
AB  - This review examines some of the questions and current literature regarding
      psychological factors as they affect pulmonary and rheumatologic diseases.
      Recommendations are made concerning directions for future research in these
      areas.

PMID- 2003135
TI  - Head-injured parents and their children. Psychosocial consequences of a traumatic
      syndrome.
AB  - Traumatic brain injury, a prevalent health problem in contemporary society, poses
      complex adaptational challenges for victims' families. The sequelae most
      disruptive to family functioning appear to be residual psychiatric symptoms. With
      a peak incidence among young adults, brain trauma also befalls many parents of
      dependent children; these children are vulnerable to subsequent emotional and
      behavioral difficulties. An approach to these problems must recognize the broad
      spectrum of clinical outcomes from brain injury. Valuable insights may also be
      gained from earlier work on children's responses to more familiar parental
      psychiatric disorders. Three case reports of children with head-injured parents
      are presented, followed by a discussion of treatment considerations for this
      emerging "at-risk" population.

PMID- 2003136
TI  - Psychotropic drug use in the medically ill. Part II.
AB  - Underlying medical illness and drug interactions may make the use of psychotropic
      agents problematic in some physically ill patients. This overview, published in
      two parts, discusses six major classes of psychotropic medications (cyclic
      antidepressants, monoamine oxidase inhibitors, benzodiazepines, neuroleptics,
      lithium, psychostimulants, and carbamazepine) and examines their use in the
      setting of specific types of medical illnesses (e.g., cardiovascular, pulmonary,
      hepatic, and renal disease). Practical considerations in using psychotropic
      medications in medical-surgical patients--particularly those who are elderly or
      medically debilitated--will receive special emphasis.

PMID- 2003137
TI  - Theophylline reversal of electroconvulsive therapy (ECT) seizure inhibition.
AB  - Oral sustained-release theophylline 200-400 mg, given 10 hours prior to
      electroconvulsive therapy (ECT) increased ECT seizure length in each of eight
      male patients who had shown unacceptably short seizures. The increase was on
      average 13.9 (+/- 6.0, SD) sec (p = .00016 by t test; p = .0000034 by exact
      probability). The absence of unduly prolonged seizures was attributed to
      previously demonstrated high seizure thresholds and to relatively low
      concentrations of theophylline. No adverse effects from theophylline were seen.

PMID- 2003138
TI  - Psychological and behavioral factors affecting medical conditions and DSM-IV. An
      overview.
AB  - As part of the process of reevaluating the category Psychological Factors
      Affecting Physical Condition (PFAPC) for possible revisions in DSM-IV, a
      coordinated review of the literature was conducted to document the extent of
      empirical evidence that exists for an association between psychological factors
      affecting the onset, exacerbation, course, and outcome of medical disorders. In
      this introduction and overview, the authors discuss the methodology and purpose
      of the reviews, as well as the reasons for considering revisions in the PFAPC
      category. Relevant historical concepts in psychosomatic medicine are briefly
      reviewed, and an argument is made that the general scope of the PFAPC category
      should be broadened in DSM-IV to include behaviorally related factors of major
      public health concern, as well as the effects of psychiatric comorbidity on
      medical outcome.

PMID- 2003139
TI  - The link between fluid intake and weight gain in psychosis.
AB  - Diurnal weight gain was found to be abnormal among 44 of 77 institutionalized
      chronically psychotic patients. All patients were weighed and urine samples
      obtained weekly for 3 weeks at 7 A.M. and 4 P.M. Diurnal weight gain was
      normalized as a percentage by subtracting the 7 A.M. weight from the 4 P.M.
      weight, multiplying the difference by 100, and then dividing the result by the 7
      A.M. weight. Normalized diurnal weight gain (NDWG) was 2.504 +/- 1.266% for the
      44 study patients with abnormal findings, .631 +/- .405% for the 16 acutely
      psychotic controls, and .511 +/- .351% for 29 normals. Urine excretion was
      related (r = .476, p = .001) to NDWG in the subgroup of study patients with
      abnormal NDWG, consistent with the observation that their fluid intake exceeded
      fluid excretion in the afternoon.

PMID- 2003140
TI  - Psychiatric morbidity following implantation of the automatic implantable
      cardioverter defibrillator.
AB  - The automatic implantable cardioverter defibrillator (AICD) has found a place in
      the treatment of sustained ventricular tachycardia and in survivors of sudden
      arrhythmic death. However, little is known about the psychological impact of this
      device on patients and their families. In a group of 20 AICD recipients, examined
      between 3 and 21 months post-implantation, the prevalence of psychiatric disorder
      was 50%. Following implantation, six patients suffered from adjustment disorder;
      three suffered from major depression; and one developed panic disorder.
      Psychiatric morbidity in patients was associated with psychopathology in family
      members, peri-operative AICD shocks, and social support that was perceived to be
      inadequate.

PMID- 2003141
TI  - A retrospective study of psychosocial morbidity in bone marrow transplant
      recipients.
AB  - Of the 44 bone marrow transplant recipients asked to participate in this study,
      33 completed psychometric instruments. Twenty-five patients had both unstructured
      clinical interviews and interviews using a structured diagnostic instrument (the
      Composite International Diagnostic Interview). There were no differences between
      allogeneic and autogenic transplant recipients. Overall, patients demonstrated
      adjustment comparable with other medical patients. A high prevalence of
      depression (40%) was shown to be associated with impaired function. The
      implications of these findings are discussed.

PMID- 2003142
TI  - The clinical assessment of the cardiac transplant candidate.

PMID- 2003143
TI  - Delusional parasitosis in geriatric patients.

PMID- 2003144
TI  - Cyclosporine-associated organic mental disorders in liver transplant recipients.
AB  - The cases presented here, along with a preliminary body of clinical literature,
      suggest that, in conjunction with other factors, cyclosporine has an etiologic
      role in the production of a variety of organic mental disorders, including
      delirium, generalized anxiety disorder, hallucinosis, and organic mood disorder
      depressed. The cases in this report were chosen in part because they illustrate
      definable organic syndromes. Other transplant recipients may experience less
      severe or isolated symptoms, such as sleep-wake reversal, insomnia, anxiety,
      lethargy, or mild confusional states that do meet full criteria for organic
      mental syndrome but that appear to be related to cyclosporine. Persecutory
      delusions may also occur in both floridly delirious patients and in patients with
      only minimal disorientation. Mental state aberrations most commonly begin within
      2 weeks of treatment with cyclosporine, and, frequently, most acute symptoms
      resolve within a few weeks of onset. However, in more severely delirious patients
      or in patients with medical courses complicated by other problems, symptoms may
      continue longer. In particular, difficulties with memory and with the acquisition
      of new information may persist for several weeks. Less commonly, mental syndromes
      may also occur following longer periods of treatment with cyclosporine.
      Individual vulnerability appears to vary widely, and many patients demonstrate
      mental complications at cyclosporine levels that are in the moderate therapeutic
      range for immunosuppression. In addition, patients who have recently been started
      on cyclosporine and who demonstrate high therapeutic, rapidly rising, or toxic
      serum levels may be at greatest risk. Other risk factors may include intravenous
      administration, hypomagnesemia, hypocholesterolemia, and concurrent
      methylprednisolone bolus.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2003145
TI  - The hemodynamics of cardiac pacing: clinical and physiological aspects.

PMID- 2003146
TI  - Cardiovascular sequelae of therapeutic thoracic radiation.
AB  - Mediastinal radiation damages endothelial cells, with resulting loss of
      capillaries and ischemia at the level of the microcirculation. These changes lead
      to increases in collagen and proliferation of fibrous tissue throughout the
      heart. Cardiac dysfunction following radiotherapy is surprisingly common and may
      be due to pericardial, myocardial, valvular, conduction system, or coronary
      artery disease. Greater awareness of cardiotoxicity has prompted changes in
      radiation techniques that appear to reduce clinical cardiovascular complications.

PMID- 2003147
TI  - Isolated pulmonary valvular regurgitation: current perspectives.
AB  - IPVR is a rare clinical entity that was first diagnosed during life in 1955. In
      the past 35 years, only 69 patients have been reported. With increasing clinical
      awareness, as well as use of PDE, the confirmation of its clinical diagnosis has
      become easier and more accurate without having to take recourse to invasive
      cardiac studies as in the past. For this reason, it is becoming increasingly
      apparent that IPVR is not so rare as has been suggested in the past. IPVR is more
      common in men than in women, in whites than blacks, and in the young than the
      elderly. The mean age of IPVR patients is 27 years (range, 4 to 85). The majority
      of the patients are asymptomatic and the diagnosis is usually suspected upon the
      discovery of a crescendo-decrescendo, low-pitched, early to mid diastolic murmur
      in the second and third left intercostal space, which increases during
      inspiration, particularly in the presence of a hyperdynamic right ventricle and
      in the absence of peripheral circulatory phenomenon of aortic regurgitation. The
      ECG often shows right axis deviation, incomplete right bundle branch block, and
      rarely, right ventricular hypertrophy and strain. However, a normal ECG does not
      preclude its diagnosis. Approximately 30% of the IPVR patients have normal 12
      lead ECGs. The diagnosis may be further suggested by the posteroanterior chest
      roentgenogram when dilated and large central pulmonary arteries are noted to
      pulsate vigorously (hilar dance) on chest fluoroscopy.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 2003148
TI  - Effects of helodermin and VIP on insulin and glucagon secretion in the mouse.
AB  - Helodermin and vasoactive intestinal polypeptide (VIP) are structurally related
      peptides. We have examined their effects on insulin and glucagon secretion in the
      mouse. Following intravenous injection, helodermin and VIP equipotently increased
      plasma glucagon levels with a maximal effect obtained at the dose level of 2
      nmol/kg. The maximal response was not augmented by giving the two peptides
      together at maximal dose levels, showing that helodermin and VIP stimulate
      glucagon secretion by activating the same mechanisms. Furthermore, both peptides
      markedly potentiated glucagon secretion stimulated by the cholinergic agonist
      carbachol, showing that they sensitize glucagon secretion for muscarinic
      activation. This sensitizing action was abolished by methylatropine, whereas the
      direct glucagonotropic action of the peptides was insensitive to muscarinic
      antagonism. Plasma insulin levels were not affected by helodermin but slightly
      increased by VIP. The study suggests that helodermin and VIP (1) stimulate basal
      glucagon secretion by the same mechanism, which is insensitive to muscarinic
      antagonism, (2) sensitize the glucagon secretion for cholinergic activation, and
      (3) have no or only weak effect on insulin secretion.

PMID- 2003149
TI  - Circulating endothelin influences area postrema neurons.
AB  - The recently described endothelium-derived constricting factor endothelin (ET) is
      a 21 amino acid peptide which is the most potent endogenous vasoconstrictor yet
      described. Binding sites for this peptide have been demonstrated within the
      circumventricular structures of the brain. One of these structures, the area
      postrema (AP), has been implicated in central cardiovascular control mechanisms.
      We have recently demonstrated that microinjection of ET into this structure
      results in dose-dependent changes in mean arterial blood pressure. The present
      studies were undertaken to test the hypothesis that ET elicits these effects as a
      result of influences on the activity of AP neurons. Using extracellular single
      unit recording techniques we have examined the effects of systemic administration
      of ET on the activity of AP neurons. A total of 60 AP neurons were tested for
      effects of ET (0.1-10.0 pmol) of which the spontaneous activity of 32 showed
      rapid (modified frequency of action potentials in the 60s following ET),
      reversible (return to baseline activity within 10 m) responses to this peptide.
      The initial response of the majority (84%) of AP neurons influenced by ET was
      excitatory, while a smaller proportion of AP neurons were inhibited (16%) by
      systemic administration of this peptide. We have also examined whether such
      excitatory effects were specific to AP neurons by comparing the above response
      characteristics to those observed in neurons in the adjacent commissural NTS.
      Such recordings demonstrated predominantly inhibitory (84% of influenced cells)
      responses of this group of NTS neurons to ET. While these findings demonstrate
      specific excitatory effects of systemic ET on the activity of AP neurons they
      also suggest a potential role for this peptide in controlling the activity of NTS
      neurons. These studies provide evidence that circulating ET influences AP
      neuronal function, although they offer no definitive information as to the
      specific site of action.

PMID- 2003150
TI  - Rhesus monkey gastroenteropancreatic hormones: relationship to human sequences.
AB  - The amino acid sequences of the gastroenteropancreatic peptides of Old World
      mammals are generally well-conserved. However, only the glucagons and vasoactive
      intestinal polypeptides (VIP) have been shown to be identical among the species
      studied to date. Rhesus monkey (Macaca mulatta) insulin has been shown to be
      identical with human insulin. The question addressed in this study is whether
      other gastroenteropancreatic peptides are identical to the human peptides.
      Purification and sequencing of glucagon, pancreatic polypeptide, VIP and insulin
      confirmed their identity with the corresponding human peptides. However, the 17
      amino acid monkey gastrin is identical to dog gastrin and differs from human
      gastrin by substitution of methionine for leucine at position 5 from the N
      terminus and alanine for glutamic acid in position 10. If additional rhesus
      monkey tissues become available, it would be of interest to determine whether
      other gastrointestinal peptides also differ from the corresponding human
      peptides.

PMID- 2003151
TI  - Pancreatectomy, amino acids and glucagon: effect on canine renal autoregulation.
AB  - Using pancreactectomized (PX) dogs, we recently suggested the importance of
      glucagon in modulating amino acid-induced increases in renal blood flow (RBF) and
      glomerular filtration rate (GFR). We have now ascertained whether glucagon's
      modulatory effect is associated with an impairment in renal autoregulation. As
      renal arterial pressure (RAP) was reduced to 70 mmHg (the lower limit of the
      autoregulatory range) in both sham-operated control (C) and PX control dogs, RBF
      and GFR remained at values that were greater than 90% of their respective
      controls. In control dogs infused with amino acids (0.051 mmol/kg per min, i.v.),
      RBF and GFR rose by 26 and 27%, respectively, at baseline RAP. As RAP was reduced
      to 70 mmHg, RBF and GFR fell by 25 and 37%, respectively. In PX dogs infused with
      either amino acids or glucagon (0.86 pmol/kg per min, i.v.) alone, RBF and GFR
      did not increase appreciably at baseline RAP. As RAP was reduced to 70 mmHg in
      these dogs, RBF and GFR remained at values that were greater than 90% of their
      respective controls. Yet, in PX dogs infused simultaneously with amino acids and
      glucagon, RBF and GFR rose by 22 and 24%, respectively, at baseline RAP.
      Moreover, as RAP was reduced to 70 mmHg, RBF and GFR fell by 22 and 31%,
      respectively. These data suggest that the ability of glucagon to modulate the
      renal hemodynamic response to amino acid infusion involves an impairment in renal
      autoregulation.

PMID- 2003153
TI  - Genes, brain and behavior.

PMID- 2003152
TI  - Advances in medical genetics in the past 30 years.

PMID- 2003154
TI  - Mitochondrial genes and neuromuscular disease.

PMID- 2003155
TI  - Muscular dystrophy research: what have we learned and where do we go from here?

PMID- 2003156
TI  - Genetics of Alzheimer's disease.

PMID- 2003157
TI  - The current status of linkage studies in schizophrenia.

PMID- 2003158
TI  - Genetics of manic depressive illness: current status and evolving concepts.
AB  - The bipolar affective spectrum is clinically heterogeneous and genetically
      complex. Current methods for assessment and analysis of familial traits with
      variable phenotypic expression and unclear mode of inheritance are reviewed.
      Recent evidence for a major gene localized on the X-chromosome is presented and
      other linkage findings are discussed. The limitations and prospects of
      psychiatric genetics are discussed in the light of recent advances in diagnostic
      nomenclature, statistical genetic techniques, and molecular biology.
      Methodological uncertainties notwithstanding, the powerful new techniques in
      genetic research portend well for unraveling the genetics of bipolar affective
      illness.

PMID- 2003159
TI  - Behavioral genetics.

PMID- 2003160
TI  - The chromosome, its anatomy, and its aberrations.

PMID- 2003161
TI  - Genetic contributions to human obesity.
AB  - Surprisingly, until the very recent past almost nothing had been known about
      genetic influences on human obesity. The powerful genetic effects described with
      such assurance in the textbooks were based almost entirely on extrapolation from
      animal studies. The first strong evidence of genetic influence on human obesity
      was obtained from an adoption study in Denmark that showed a high correlation of
      the body mass index of adoptees with that of their biological parents and no
      correlation with that of their adoptive parents. The body mass index of the
      adoptees was also highly correlated with that of their siblings and showed
      evidence of recessive transmission. These findings have been extended by a twin
      study that revealed very high heritabilities at both age 20 and age 45. A
      bivariate analysis of the identical twins of this population revealed high
      intrapair correlations among the normal weight twins and low correlations among
      the obese twins distributions, suggesting a strong environmental influence on the
      genetically vulnerable obese twins. The best estimate of heritability, the
      correlation coefficient of 93 identical twin pairs reared apart, from the Swedish
      Adoption Study of Aging, revealed high levels of heritability, indicating that
      traditional twin studies have overestimated the heritability of body mass index
      only slightly, if at all.

PMID- 2003162
TI  - The genetics of alcoholism.

PMID- 2003163
TI  - Genetic variation and the meiotic process.

PMID- 2003164
TI  - Formal genetics in humans: mendelian and nonmendelian inheritance.

PMID- 2003165
TI  - [What is your roentgen diagnosis? Supra-patellar lipohemarthrosis with intra
      articular tibial head fracture].

PMID- 2003166
TI  - [Chronic hemorrhagic pleural effusion in mediastinal pancreatic pseudocyst].
AB  - A 48-year-old patient is presented with chronic hemorrhagic pleural effusion due
      to a pancreatitis-induced pseudocyst. High levels of pleural fluid amylase and
      demonstration of the pseudocyst by endoscopic retrograde cholangio
      pancreatography (ERCP) provided the diagnosis. After chest tube draining for
      about two weeks curative surgery was undertaken.

PMID- 2003167
TI  - [Psychosomatic treatment of patients with Crohn disease].
AB  - Only few clinical reports must suffice at present to assume that in patients with
      Crohn's disease like in those with ulcerative colitis psychotherapy--regardless
      how intensive it might be--has not been proven to cure the underlying biologic
      disturbance. Therefore the hope of complete cure by psychotherapy is not
      warranted. While improvement and even freedom of all symptoms may take place,
      psychotherapy cannot prevent stress-related relapse.

PMID- 2003168
TI  - [Vomiting, fatigue, dizziness, cold hypersensitivity and hyperpigmentation].
AB  - Vomiting, fatigue, hyperpigmentation and cold intolerance were the clinical
      symptoms of a autoimmune polyendocrinopathy type II, confirmed by laboratory
      results. One year after starting a therapy with L-thyroxine and cortisone the
      patient feels well.

PMID- 2003169
TI  - [A case from practice (206). Pulmonary arterial hypertension due to chronic
      pulmonary embolisms].

PMID- 2003170
TI  - [General practice: between academic medicine and alternative medicine?].
AB  - Academic medicine has continuously changed from a medical art into a
      technological science. As a consequence, so called alternative methods became
      increasingly popular, being regarded as a more human and comprehensive medicine.
      This article tries to give advice how the practitioner could find his position in
      between the different concepts.

PMID- 2003171
TI  - [Thoracic pain and esophageal motility disorders].
AB  - These last years the clinical relevance of oesophageal disorders in the problem
      of chest pain has been more accurately defined. After exclusion of cardiac
      diseases with appropriate tests and of organic lesions of the oesophagus with
      upper endoscopy, the physician should look for: a gastro-oesophageal reflux
      disease with a 24-hour pH-metry, if possible coupled with a 24-hour oesophageal
      manometry. An oesophageal motor disorder, for example a diffuse spasm, with
      manometry with a provocation test. Confronted with disturbing chest pain, the
      capacity to determine their oesophageal origin represents not only a diagnostic
      but also a therapeutic help.

PMID- 2003172
TI  - [Rheumatoid arthritis: what do patients do with our prescriptions?].
AB  - This study encompassing a sample of 103 out-patients with chronic polyarthritis
      revealed that only 71.6% of the patients showed good compliance with the
      prescribed medication. A relatively large cohort (61%) used paramedical
      treatments. Factors influencing compliance-behavior, in particular attitude to
      paramedical methods are investigated.

PMID- 2003173
TI  - [Tuberculosis: victory after 100 years?].
AB  - In the middle of the 19th century first signs for decrease of the epidemic
      importance of tuberculosis were obvious. Now, little more than 100 years after
      the detection of the pathogen by Robert Koch, the rate of decline suggests
      'virtual eradication' of the disease around the year 2025. However, the endemic
      disease is still prominent in different parts of the third world. Also the
      appearance of the HIV-virus revives problems of tuberculosis, especially in
      countries where a young population is afflicted by both diseases.

PMID- 2003174
TI  - [Judicious use of anorectics].
AB  - Physicians treating adipose patients often hesitate to include drugs. Considering
      new developments in obesity research and drug-therapy, this attitude should be
      discussed. Anorectics of the amphetamine-group and analogues (derivates) react
      with the noradrenergic system and induce appetite-suppression. Fenfluramine in
      the d-1 configuration and isomeric dextro-rotation influence release of
      serotonin, reduce intake of food and increase sensation of saturation. In
      addition, various eating behavior disorders like nibbling and addiction to sweets
      are discussed. Use of Dextro-fenfluramine for these special situations is
      discussed as well as its side effects, duration of drug intake and form of
      application. Importance of concomitant therapeutic means like hypocaloric diet
      and personal attendance are emphasized.

PMID- 2003175
TI  - [Apatite tenosynovitis of the hand].
AB  - Three cases of apatite tenosynovitis of the hands are presented. This rare
      condition has often a dramatic outset with an intense inflammation that could
      suggest an infectious process. The radiographic feature is characteristic, and
      the examination of the material removed from synovial sheath or from calcific
      deposits allows apatite crystals to be identified. The process is self-limited,
      but immobilization and local infiltrations of steroids shorten the duration of
      disability.

PMID- 2003176
TI  - [A difficult diagnosis].
AB  - We describe the case of a patient suffering from relapsing abdominal pain and
      vomiting over 4 years, in whom various radiological and endoscopic examinations
      remained normal. CT scan and MRI eventually showed a mesenteric mass
      corresponding to metastasis of an ileal carcinoid; this tumor was diagnosed only
      at laparotomy as well as his mesenteric and hepatic metastases. The different
      localization and clinical manifestations of carcinoid tumours as well as the
      difficulties of radiological diagnosis of tumours of the small bowel are
      mentioned; the diagnostic value of sonography. CT-scan and MRI in the diagnosis
      of hepatic metastasis is discussed.

PMID- 2003177
TI  - [50 years of medical progress and its consequences].
AB  - In 1940, a new era begins: the victorious fight against infectious diseases with
      the discovery of the first and powerful antibiotics, then the eradication of
      small-pox and poliomyelitis with new vaccines. New procedures have allowed the
      production of very efficient medicines for all the organs; if they do not
      succeed, then we can perform organ transplantation. After eliminating the natural
      selection, medicine will be able to practice predictivity through the study of
      the human genome followed by the possibility of a true prophylaxis through
      genetic manipulations which have just started a few months ago.

PMID- 2003178
TI  - [What is your diagnosis? Secondary aorto-enteric fistula].

PMID- 2003179
TI  - Elective treatment of the neck in cancer of the oral tongue.
AB  - Management of the clinically negative neck in patients with carcinoma of the oral
      tongue remains a complex and controversial subject. While statistical proof of
      the value of elective neck dissection in tongue cancer remains elusive, the high
      incidence of occult cervical metastases, even with small primary tumors, and the
      poor salvage rates and increased incidence of extracapsular spread in cases that
      have developed palpable adenopathy, provide a logical basis for treatment of the
      neck in a preclinical stage.

PMID- 2003180
TI  - Cervical metastases from an occult primary site.
AB  - Less than 5% of patients with metastatic cervical carcinoma will not have a
      detectable primary site despite a proper work-up. Recent aids for these
      diagnostic problems include fine needle aspiration and immunohistochemical panels
      to differentiate undifferentiated carcinoma from melanoma and/or lymphoma. CT
      scanning can suggest areas in the upper aerodigestive tract for biopsy and can be
      helpful in suggesting the pathology of the enlarged lymph nodes. EBV titers are
      often elevated when a nasopharyngeal carcinoma is small. Aggressive treatment of
      the occult primary patient with metastatic melanoma, thyroid cancer, and
      metastatic cancer presumed to arise from the skin of the head and neck or the
      mucous membranes of the upper aerodigestive tract is indicated as long-term
      survival is often achieved.

PMID- 2003181
TI  - Diagnosis and pitfalls in the treatment of parotid tumors.
AB  - Any swelling near the ear is best considered a parotid neoplasm until proved
      otherwise. The diagnosis is primarily based on the clinical examination. Imaging
      studies are best reserved for patients who present with palate or tonsil
      swellings, which must be distinguished from parapharyngeal or minor salivary
      gland tumors. Almost all benign, and most malignant parotid tumors can be
      resected with preservation of the facial nerve. Aspiration biopsy can add useful
      information, but is not essential for treatment planning as the extent of the
      surgical procedure is primarily determined by the extent of the tumor. Survival
      rates in patients with malignant tumors are most significantly influenced by
      tumor stage. Results seem to have improved in recent years, possibly because we
      are treating a larger proportion with favorable lesions. Another factor may
      relate to the enhancement of locoregional control now achieved with postoperative
      radiotherapy, particularly in patients with Stage III or IV tumors.

PMID- 2003182
TI  - Mandibulotomy and mandibulectomy in difficult tumors of the base of the tongue
      and oropharynx.
AB  - Wide exposure of the tumors of the base of the tongue and oropharynx can be
      easily obtained via mandibulotomy, which provides equally good exposure for
      tumors of the posterior oral cavity and oropharynx. Segmental mandibulectomy can
      be avoided in patients where the tumor does not invade the mandible or is not in
      close proximity of the mandible. Preoperative work-up may include evaluation by
      means of the fiberoptic telescope to determine the extent of the tumor,
      examination under anesthesia, panoramic X-ray of the mandible, CT scan and MRI,
      as well as dental evaluation. Tracheostomy provides airway during the operation
      and tracheobronchial access for clearance of pulmonary secretions
      postoperatively. The technique for median labiomandibuloglossotomy is described,
      as well as the mandibular swing approach and mandibulectomy. Cosmetic deformity
      after segmental mandibulectomy is minimal but mandible reconstruction should
      nonetheless be considered based on the extent of the tumor, tumor control, and
      the need for postoperative radiation therapy.

PMID- 2003183
TI  - Controversies in the diagnosis and treatment of early carcinoma of the larynx.
AB  - Patients in whom the diagnosis of early carcinoma of the larynx is made and
      treated as outlined below have a good to excellent outlook (from 85 to 95%
      survival for glottic lesions). Metastases from lesions of the free edge of the
      vocal cord usually do not occur because of the paucity of lymphatics, whereas
      lesions of the supraglottis are more apt to metastasize to regional lymph nodes
      and local spread. The subglottic area on the other hand by in large has a more
      ominous prognosis. Carcinoma in situ is treated mainly by endoscopic surgery,
      whereas T1 lesions of the glottis can either be treated by surgery or radiation
      with comparable results. This author prefers conservation surgery for the
      majority of T1 lesions. Radiotherapy is utilized for selected patients with T1
      glottic lesions.

PMID- 2003184
TI  - Advances in radiation therapy for head and neck cancer.
AB  - Radiation therapy either as a single modality or as part of multimodality plans
      remains an integral part of curative treatment for cancers of the head and neck.
      This paper traces the modernization of radiation therapy regarding tumors of the
      head and neck using examples of sites of malignancy where radiation therapy is
      the sole modality or where radiation therapy can be combined with surgery and
      chemotherapy for optimal results. As local-regional control rates have improved
      with the use of combined radiation therapy and surgery and aggressive
      hyperfractionation schemes for advanced primary tumors, distant metastases and
      second primary neoplasms are now accounting for a larger proportion of treatment
      failures. Until such time as more effective systemic therapy and cancer control
      mechanisms are developed to address these problems, radiation therapy will
      continue to play a major role in the overall management of patients with cancers
      of the head and neck.

PMID- 2003185
TI  - Current advances in reconstruction of the mandible in head and neck cancer
      surgery.
AB  - Today's reconstruction of head and neck cancer related deformities is based on an
      in-depth knowledge of soft and hard tissue repair coupled with the technical
      ability to transplant and reorient soft and hard tissues into a functional and
      cosmetic improvement for each patient. The recent advances of (1) the science of
      bone regeneration, (2) myocutaneous flaps, (3) hyperbaric oxygen, and (4)
      allogeneic bone cribs have resulted in reconstructions which are now predictable
      outcomes with few complications and minimal morbidity. This writing will discuss
      the contribution and mechanism of each of these four advances and how their
      application can be used to consistently reconstruct even large deformities with
      both hard and soft tissue loss, as well as in tissues which have been severely
      radiated.

PMID- 2003186
TI  - Neck dissection: concepts, controversies, and technique.
AB  - The various types of neck dissections are described. The indications for each
      type of neck dissection are discussed for patients with necks staged N0, N+, for
      the patient with an unknown primary and for the patient whose neck dissection is
      in conjunction with radiation. The technical aspects of modified neck dissections
      are addressed but not in great detail. The indications for the use of
      postoperative radiation are emphasized. The nodal groups at risk for metastases
      from various primary sites are identified and a terminology for neck dissection
      is suggested.

PMID- 2003187
TI  - Aging in Rhode Island: the physical, psychological, and social challenges of the
      21st century.

PMID- 2003188
TI  - Older Rhode Islanders: demography, health status and the implications for the
      practice of medicine.
AB  - There is a large and growing elderly population in Rhode Island and that
      population is getting older. Rhode Island's elders are maldistributed
      geographically and represent a larger proportion of the population than
      nationally. Most have significant chronic conditions and many have major
      limitations in functional abilities. Relatively few reside in long-term care
      facilities and generally, the community-dwelling population rates their health
      favorably. The elderly in Rhode Island make more physician visits than any other
      segment of the population and account for a disproportionate number of hospital
      and nursing home days. The number of primary care physicians practicing adult
      medicine in Rhode Island has diminished and if the trends of graduating medical
      students continue, further decreases are to be expected. The costs of health care
      for the elderly in Rhode Island have skyrocketed over the last 20 years, and are
      projected to continue to increase dramatically over the next 40-50 years in part
      as a result in the growth of the state's elderly population. These cost increases
      will be magnified if health care costs in general continue to outpace other
      segments of our economy. If Rhode Island is to adequately meet the health care
      needs of older Rhode Islanders over the next 40-50 years, major changes must
      occur. Initiatives to prevent or forestall the onset of chronic illnesses and
      resultant functional limitations are likely to improve the quality of life of
      older Rhode Islanders as well as positively influence the costs of health care
      for this segment of our state's population.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2003189
TI  - Common mental health problems in geriatric practice. Part I: Dementia,
      depression, anxiety, and prescription drug toxicity.

PMID- 2003190
TI  - Common mental health problems in geriatric practice. Part II: Insomnia, chronic
      pain, troubled families, and other dilemmas.

PMID- 2003191
TI  - Falls.
AB  - Falls occur commonly enough in community-dwelling elderly, and have sufficient
      morbidity and mortality, to argue for increased recognition of the problem by
      physicians. Whereas in the past these falls may have been considered an
      inevitable part of aging, it is now clear that distinct risk factors can be
      identified. Physicians can evaluate patients by using relatively simple
      assessment tools, including the history, physical examination and, most
      importantly, direct observation of position changes and gait maneuvers used in
      everyday activities of daily living. Interventions to prevent falls can be based
      on the individual assessment of risk factors. The implications of effective
      preventive practices for Rhode Island are substantial given the relatively high
      percentage of older persons in the state and the limited long term care
      facilities required to care for the older person whose decline in function
      follows a fall.

PMID- 2003192
TI  - Assessment of disruptive behavior in the nursing home: stories and strategies.

PMID- 2003193
TI  - Ageism among physicians: fundamental questions.

PMID- 2003194
TI  - Malpractice litigation and the physician.

PMID- 2003195
TI  - Injury mortality among the elderly.

PMID- 2003196
TI  - HIV testing: whose rights should prevail?

PMID- 2003197
TI  - When our patients get up is our decision.

PMID- 2003198
TI  - Rx for spiritual distress.

PMID- 2003199
TI  - When your patient needs a stress test.

PMID- 2003200
TI  - Patient teaching for x-ray and other diagnostics. Stress test and thallium stress
      test.

PMID- 2003201
TI  - Hypotension: the other side of the coin.

PMID- 2003202
TI  - Interpreting ABGs.

PMID- 2003203
TI  - Nursing the mind. Recognizing post-traumatic stress.

PMID- 2003204
TI  - FDA approvals. New drugs, new uses.

PMID- 2003205
TI  - Giving a deposition? Don't be caught off guard.

PMID- 2003206
TI  - Becoming a vegetarian: the risks and the benefits.

PMID- 2003207
TI  - [Pulmonary complications in cystic fibrosis].
AB  - As a result of better control and improved symptomatic lung therapy, more than
      half of cystic fibrosis patients reach the age of twenty. With increasing age and
      progression of lung disease complications become more frequent. The pulmonologist
      treating the adult patients must therefore be aware of them and treat them
      adequately. The present study discusses the diagnosis and therapy of (i.e.
      bronchial hyperreactivity, mucoid impaction, pneumothorax, lung bleeding and,
      finally, pulmonary hypertension).

PMID- 2003208
TI  - [Pneumonia: identification of respiratory pathogens].
AB  - The etiological diagnosis of pneumonia is necessary because it will condition
      therapy. The broad spectrum of potential pathogens is reduced when the host's
      condition and the events around the pneumonia episode are taken in account.
      Community acquired pneumonia in an immunocompetent host most often is caused by
      bacteria (predominantly S. pneumoniae) or by mycoplasma or respiratory viruses.
      Microbiological diagnosis relies on direct sputum examination and culture (for
      bacterial agents) and on serology (for nonbacterial agents). In a compromised
      host, the spectrum of etiological agents is broader; sputum examination often is
      unrewarding and invasive investigations are necessary. Bronchoscopy with
      bronchoalveolar lavage is increasingly used, allowing an abundant material to be
      analyzed with a battery of tests directed against the pathogens most probable in
      view of the clinical setting. Direct examinations with special stains for
      bacteria, fungi, parasites, and viruses offer a rapid diagnosis in some cases.
      Various cultural procedures for bacteria, viruses and fungi, particularly in the
      absence of previous antimicrobial therapy, will establish the etiological
      diagnosis in the majority of pneumonia cases and help to select specific therapy.

PMID- 2003209
TI  - Applications of cell and molecular biology to pneumonology.
AB  - I briefly review comments I made concerning recent advances in techniques of cell
      and molecular biology, including molecular cloning and characterization of genes,
      gene therapy, and newer applications of these techniques to the study of lung
      disease during the 1990 annual meeting of the Swiss Society of Pneumonology.
      Recent preliminary findings from my own laboratory utilizing the example of
      immunohistochemical and in situ hybridization techniques to study connective
      tissue and cytokine growth factor expression and remodeling in human pulmonary
      fibrosis are also discussed.

PMID- 2003210
TI  - [Immunoglobulin deficiency after repeated plasmapheresis].
AB  - In 10 patients with Guillain-Barre syndrome the level of globulins and
      immunoglobulins before and after plasmapheresis was investigated. As a plasma
      substitute either PPL (in 8 patients) or a plasma substitute solution rich in
      immunoglobulins (in 2 patients) was used. When plasma was substituted with PPL,
      the globulins and immunoglobulins dropped to a mean of 40% of the initial value
      (range 30-60%) after the first plasmapheresis. With daily or alternate day
      plasmapheresis, the globulins only partially recovered. Before the second
      plasmapheresis they were still reduced to a mean of 50% (range 20-50%), and
      dropped further with ongoing exchanges to a mean of 33% (range 20-50%) as
      measured before the third plasmapheresis. Accordingly, there was a loss of
      immunoglobulins of similar magnitude. With the use of a plasma substitute
      solution rich in immunoglobulins (IRP), globulins could be maintained at normal
      levels. The lowest immunoglobulin values measured after plasmapheresis were 6 g/l
      (normal range 8-17 g/l). One patient developed gram-negative septicaemia after
      plasmapheresis with PPL, possibly due to a low immunoglobulin concentration. We
      conclude that a plasma substitute solution rich in immunoglobulins should be used
      for therapeutic plasmapheresis in order to maintain physiological immunoglobulin
      concentrations.

PMID- 2003211
TI  - [Constipation and incontinence: significance of colonic transit time, anorectal
      manometry and defecography].
AB  - Constipation and fecal incontinence are frequent motives of gastroenterological
      consultation. An etiological diagnosis can often be suspected from the history
      and can be confirmed by functional testing. We here report our experience with
      the measurement of colonic transit time (TTC), anorectal manometry (MAR) and
      defecography (D). Whilst TTC was unhelpful, MAR revealed abdomino-pelvic
      asynchrony (anismus) in 60 constipated patients and 7 (47%) of 15 incontinent
      patients. Perineal descent was suspected in 25 constipated patients and confirmed
      by defecography, which also revealed associated static pelvic disorders. Our
      experience confirms the role of functional exploration in the investigation of
      constipation and fecal incontinence and permits a more precise therapeutic
      approach.

PMID- 2003212
TI  - [50 years of blood transfusion services of the Swiss Red Cross].
AB  - In the postwar years the Swiss Red Cross set up and developed a blood transfusion
      service based on strictly nonremunerated donation. It comprises the Blood
      Transfusion Service Central Laboratory foundation in Berne and the Swiss Red
      Cross Regional Blood Transfusion Centres association. The Central Laboratory's
      responsibilities cover provision of stable blood plasma products and transfusion
      equipment and the organization of extensive services in the entire field of
      transfusion medicine. The Regional Centres supply the country with labile
      cellular blood preparations. The growth of this organization over the last 50
      years is described.

PMID- 2003213
TI  - [Concerning "Hemiparesis and torsades de pointes with low dosage sotalol therapy"
      by C. Sieber, Ph. Weiss and F. Follath (Schweiz. med. Wschr. 1990; 120: 1397
      1399)].

PMID- 2003214
TI  - NIH misconduct procedures: effect of new ruling.

PMID- 2003215
TI  - NIH takes heat for lax investigation.

PMID- 2003216
TI  - Gallo challenged on HIV isolates.

PMID- 2003217
TI  - Science television: colleagues on cable.

PMID- 2003218
TI  - AIDS vaccine trials: bumpy road ahead.

PMID- 2003219
TI  - Peptide processing and targeting in the neuronal secretory pathway.
AB  - The abdominal ganglion of the marine mollusk Aplysia contains a pair of
      identified neuronal clusters, the bag cells, which control egg laying by means of
      a number of unique regulatory mechanisms. Each neuron in the bag cell clusters
      synthesizes several peptides derived from a single prohormone and packages them
      into separate vesicles. These vesicles are then differentially localized in
      specific neuronal processes, thus segregating peptides destined for autocrine and
      hormonal release sites. Therefore in this system, protein trafficking through the
      secretory pathway organizes multiple peptide neurochemical messengers to
      efficiently regulate simple behaviors.

PMID- 2003220
TI  - Multiple representations of pain in human cerebral cortex.
AB  - The representation of pain in the cerebral cortex is less well understood than
      that of any other sensory system. However, with the use of magnetic resonance
      imaging and positron emission tomography in humans, it has now been demonstrated
      that painful heat causes significant activation of the contralateral anterior
      cingulate, secondary somatosensory, and primary somatosensory cortices. This
      contrasts with the predominant activation of primary somatosensory cortex caused
      by vibrotactile stimuli in similar experiments. Furthermore, the unilateral
      cingulate activation indicates that this forebrain area, thought to regulate
      emotions, contains an unexpectedly specific representation of pain.

PMID- 2003221
TI  - Movement of neural activity on the superior colliculus motor map during gaze
      shifts.
AB  - The superior colliculus contains neurons that cause displacements of the visual
      axis (gaze shifts). These cells are arranged topographically in a motor map on
      which the vector (amplitude and direction) of the coded movement varies
      continuously with location. How this spatial representation becomes a temporal
      code (frequency and duration) in the motoneurons is unknown. During a gaze shift,
      a zone of neural activity moved continuously on the map from an initial location,
      defining the vector of the desired gaze shift, to a final "zero" position
      containing neurons that were active during fixation. Thus, the spatial-temporal
      transformation may be accomplished by control of gaze throughout the spatial
      trajectory of activity on the motor map.

PMID- 2003222
TI  - Second structural motif for recognition of DNA by oligonucleotide-directed triple
      helix formation.
AB  - Relative orientations of the DNA strands within a purine.purine.pyrimidine triple
      helix have been determined by affinity cleaving. A purine-rich oligonucleotide
      bound in the major groove of double-helical DNA antiparallel to the Watson-Crick
      purine strand. Binding depended upon the concentration of multivalent cations
      such as spermine or Mg2+, and appeared to be relatively independent of pH. Two
      models with specific hydrogen-bonding patterns for base triplets (G.GC, A.AT, and
      T.AT) are proposed to explain the sequence specificity of binding. The two models
      differ in the conformation about the glycosyl bond (syn or anti) and the location
      of the phosphate-deoxyribose backbone in the major groove of DNA. This motif
      broadens the structural frameworks available as a basis for the design of
      sequence-specific DNA binding molecules.

PMID- 2003223
TI  - Cisplatin update.

PMID- 2003224
TI  - Cisplatin in advanced cancer of the cervix: an update.
AB  - Cisplatin is the single most active cytotoxic agent in the treatment of patients
      with recurrent or metastatic squamous cell cancer of the cervix; no other
      standard drug has been associated consistently with objective response rates of
      25% or higher. However, cervical cancer is a relatively drug-resistant disease
      and prolonged cisplatin treatment appears to induce multiple mechanisms of tumor
      resistance. The majority of objective responses to cisplatin are partial and
      relatively short-lived and, therefore, have little impact on survival duration.
      Complete responses to cisplatin are seen predominantly in patients with
      extrapelvic metastases rather than pelvic recurrences. This article examines the
      role of cisplatin in the management of advanced cervical cancer with emphasis on
      its efficacy in the following circumstances: as a single agent; in combination
      with other cytotoxic drugs; in previously treated patients; and when administered
      before surgery or before or concurrent with definitive radiation therapy.

PMID- 2003225
TI  - Cisplatin therapy for adenocarcinoma of the stomach.
AB  - Cisplatin-based chemotherapy has most recently emerged as among the most active
      combinations for patients with disseminated or locally unresectable
      adenocarcinoma of the stomach. This article provides the historical framework for
      understanding these trials. It reviews the results of clinical trials using
      cisplatin alone or in combination in almost 600 patients. Because a recent German
      trial has suggested that cisplatin in combination with etoposide and doxorubicin
      increases gastric cancer resection rates, the rationale for cisplatin combination
      therapy in the neoadjuvant setting now has a foundation. Preliminary results from
      such a neoadjuvant approach used at the University of Southern California Medical
      Center are discussed. Finally, new areas of clinical and laboratory research in
      the treatment of gastric cancer are outlined as possibilities for future studies
      of the therapy of gastric cancer.

PMID- 2003226
TI  - The role of cisplatin in treatment regimens for squamous cell carcinoma of the
      head and neck.
AB  - Advanced squamous cell carcinoma of the head and neck (SCCHN) is both a local
      regional and a systemic disease that is ineffectively managed by conventional
      surgery and radiotherapy. For patients with advanced but potentially curable (Mo)
      disease, the morbidity associated with conventional surgery or radiotherapy may
      be significant whereas the probability of lasting disease control is low. For
      those with recurrent or metastatic lesions, surgery or radiotherapy are rarely
      effective options. In this setting, chemotherapy has been evaluated as primary
      therapy for patients with recurrent or metastatic disease and as an adjunct to
      surgery or radiotherapy for those with potentially curable lesions. As palliative
      therapy, methotrexate remains the single agent of choice. Combination
      chemotherapy has been associated with a higher response rate but not improved
      survival when compared with methotrexate alone. Cisplatin, both as a single agent
      and in combination with 5-fluorouracil, is active against SCCHN, and may be
      superior to methotrexate in antitumor activity. The impact of induction and
      adjuvant chemotherapy or concurrent chemotherapy and radiotherapy in patients
      with potentially curable lesions remains controversial. A specific role for
      chemotherapy has not been confirmed by prospective randomized trial, but
      effective therapies have been achieved: Regimens with increased activity against
      squamous carcinomas have been reported, clinical trials with sufficient power to
      reach significant conclusions have been published, and organ preservation has
      been confirmed as an appropriate end point for studies of induction chemotherapy
      or concurrent chemotherapy and radiation. The clinical experience with
      chemotherapy for patients with recurrent or metastatic SCCHN as well as induction
      and adjuvant chemotherapy and concurrent chemotherapy and radiotherapy for those
      with potentially curable disease is reviewed, with particular emphasis given to
      trials involving cisplatin and to avenues for continued clinical investigation.

PMID- 2003227
TI  - Intraperitoneal cisplatin-based chemotherapy for ovarian carcinoma.
AB  - Ovarian carcinoma demonstrates a steep dose-response curve for cisplatin, but
      even very small levels of acquired resistance at the cellular level are
      sufficient to block the efficacy of intravenous (IV) cisplatin. The
      intraperitoneal (IP) route of administration produces a 12-fold to 15-fold
      greater exposure for the peritoneal cavity, and concurrent use of IV thiosulfate
      permits the safe IP injection of 200 mg/m2 cisplatin. In this study, two phase II
      trials of an IP regimen containing cisplatin 200 mg/m2 and etoposide 350 mg/m2
      with IV thiosulfate were conducted; the first trial enrolled patients with
      residual disease less than 2 cm who had failed primary cisplatin-based IV
      chemotherapy and the second trial newly diagnosed ovarian carcinoma patients
      irrespective of the size of residual disease after primary surgery. As salvage
      therapy, the IP cisplatin/etoposide regimen produced a median survival of 26
      months from the start of IP therapy and 51 months from diagnosis. As first-line
      therapy, the median survival has not yet been reached; projected survival is 68%
      at 27 months. In both studies the major toxicity was myelosuppression; the use of
      concurrent thiosulfate almost completely eliminated serious nephrotoxicity and
      neurotoxicity. The size of the largest tumor mass was an important determinant of
      efficacy in both settings. The results of these trials are consistent with the
      hypothesis that increased drug delivery will result in higher response rates and
      improved survival. Data are sufficiently encouraging to mandate phase III
      randomized trials of this program.

PMID- 2003228
TI  - Cytotoxic chemotherapy for advanced bladder cancer: cisplatin-containing
      regimens.

PMID- 2003229
TI  - Experience with cisplatin in treatment regimens for esophageal cancer.
AB  - This article reviews the rationale for chemotherapy (especially cisplatin-based
      treatments) in the management of epidermoid tumors of the esophagus. It focuses
      on the history of cisplatin and cisplatin-based combinations in the treatment of
      metastatic and localized esophageal cancers. The seminal chemotherapy trials of
      investigators at Memorial Sloan Kettering Cancer Center are reviewed and placed
      into perspective as a body of work that systematically measured the effects of
      chemotherapy in the treatment of primary tumors within the esophagus. The Wayne
      State University (Detroit, MI) program and subsequent similar programs, combining
      chemotherapy with concomitant radiation, are also reviewed and placed into
      historical context. Recently completed prospectively randomized cooperative group
      trials have now shown that chemotherapy in addition to radiation improves
      survival of patients with localized esophageal cancers versus radiation alone.
      While no standard chemotherapeutic regimen has come to the fore, chemotherapy
      clearly has a role in the curative treatment of epidermoid tumors of the
      esophagus.

PMID- 2003230
TI  - Serotonin antagonists in the management of cisplatin-induced emesis.
AB  - Cisplatin is recognized as an active chemotherapeutic agent in a broad variety of
      human tumors. The severe emetic effects of cisplatin, however, result in both
      acute and delayed emesis syndromes causing considerable morbidity. Over the last
      decade, the standard of therapy for control of cisplatin-induced emesis has been
      high-dose metoclopramide. Unfortunately, approximately 30% of cisplatin-treated
      patients experience emesis despite metoclopramide-based combination antiemetic
      therapy. Further, metoclopramide itself is associated with side effects, in
      particular, extrapyramidal reactions that may lead to patient refusal of further
      chemotherapy. This review describes the current development status of a new class
      of antiemetics, the serotonin antagonists, that have demonstrated efficacy in
      preventing cisplatin-induced nausea and vomiting. In addition to a high degree of
      effectiveness, these agents are characterized by a low incidence of significant
      side effects and the complete absence of extrapyramidal reactions. Their
      introduction into clinical use should add substantially to the practicing
      oncologist's therapeutic armamentarium and improve the quality of life of
      patients treated with cisplatin.

PMID- 2003231
TI  - The integration of platinum and radiotherapy in the treatment of lung cancer.
AB  - Combined-modality therapy in lung cancer is a common practice throughout the
      world. The use of radiochemotherapy appears to be firmly established in the
      treatment of small cell lung cancer, but the role of prophylactic cranial
      irradiation remains undecided. Many recommend its use in the treatment of non
      small cell lung cancer as well, but no facts exist to support this position.
      Because of poor long-term outcome and high frequency of systemic relapse,
      integration of chemotherapy for the treatment of non-small cell lung cancer is
      becoming more prevalent. This article discusses methods of integration, the
      problems of combined- modality toxicity, recent trials, and reports of multimodal
      therapy in lung cancer. The advantages of certain regimens of chemotherapy and
      new methods of radiotherapy are also discussed.

PMID- 2003232
TI  - Cauda equina syndrome caused by migrating fat graft after lumbar spinal
      decompression. A case report demonstrated with magnetic resonance imaging.

PMID- 2003233
TI  - Axial rotation of the lumbar spine and the effect of flexion. An in vitro and in
      vivo biomechanical study.
AB  - A series of experiments were performed on eight whole, cadaveric lumbar spines
      and on eight male volunteers to determine whether axial rotation changed with
      subjects bending forward compared with being in a neutral posture and whether
      rotation was affected by articular tropism. Kirschner wires were inserted into
      the spinous processes of the eight cadaveric lumbar spines, and the axial
      rotation of the wires was measured while the spine was rotated in a torsion
      apparatus. Similarly, Steinmann pins were inserted into the spinous processes of
      L3, L4, and L5 of the eight volunteers, and the axial rotation of the pins was
      measured while the subjects rotated in a torsion apparatus. Axial rotation was
      found to be less when combined with forward flexion, and articular tropism did
      not influence the amplitude of rotation.

PMID- 2003234
TI  - Noninvasive measurement of lumbar sagittal mobility. An assessment of the
      flexicurve technique.
AB  - The use of flexicurves to measure lumbar sagittal mobility was subjected to a
      series of reliability and validation experiments. Appropriate statistical methods
      were described and used to quantify intraobserver and intrasubject variability
      and to determine limits of agreement with measurements from radiographs. It was
      shown that the traditional use of correlation coefficients can produce misleading
      or inadequate information. The flexicurve technique had an intraobserver
      variability of 3-4 degrees of movement, was not significantly influenced by
      intrasubject variability, and provided measurements typically within 6 degrees of
      radiographic measurements. The data suggest that the flexicurve technique is less
      biased than the inclinometric method. These results demonstrate the use of
      suitable statistical methods to assess the clinical usefulness, or level of
      interchangeability, of spinal measurement instruments.

PMID- 2003235
TI  - Percutaneous nucleotomy. An anatomic study of the risks of root injury.
AB  - Fifteen cadaveric dissections have been performed to determine the anatomic
      relationships of nucleotomy guide wires. All the 44 guide wires inserted were
      found to be in contact with at least one nerve root (eight transfixed a root).
      Guide wires passing anterior to the nerve roots always passed anterior to the
      center of the disc. Lateral displacement of the skin entry point made safe entry
      to the center of the disc impossible. Nerve root transfixion is likely to be a
      significant complication in percutaneous nucleotomy. Entry to the center of the
      disc avoiding the nerve roots is simplest if the skin entry is as near to the
      midline as possible.

PMID- 2003236
TI  - Effects of chondroitinase ABC on intrathecal and peripheral nerve tissue. An in
      vivo experimental study on rabbits.
AB  - The enzyme chondroitinase ABC has recently been suggested for use in
      chemonucleolysis. The effects of 200 U ml of chondroitinase ABC were studied on
      intrathecal and peripheral nerve tissue in rabbits. After the intrathecal
      (subarachnoid) application of 0.2 ml of either the diluent in the control group
      (N = 2) or chondroitinase in the study group (N = 4), no neurologic deficit was
      detected. Compared with the control group, no morphologic changes at the light
      microscopic level were induced in the spinal cord by chondroitinase. No
      neurophysiologic differences were detected between tibial nerves after exposure
      to 1 ml of the diluent (control, N = 8) or chondroitinase (the other leg) for 4
      weeks, nor did the study group, compared with the control group, show any
      morphologic changes in the tibial nerves. Because the concentration of
      chondroitinase ABC tested was approximately 40 times higher than might be used
      clinically for chemonucleolysis, the present study indicates a wide margin of
      safety for unwanted side effects on nerve tissue.

PMID- 2003237
TI  - Postoperative cerebrospinal fluid leakage after lumbar spine operations.
      Conservative treatment.
AB  - Cerebrospinal fluid (CSF) leakage from a postoperative wound after lumbar spine
      operation is an uncommon complication. It may result from excessive traction of
      the nerve roots, direct trauma, or laceration at the time of operation, causing
      the dura to be inadvertently opened. Other reasons for this complication are
      postlaminectomy residual bone spikes, traumatic myelography puncture, and
      improper suture of dura defects. Eight patients who had postoperative CSF leakage
      as the only complication after lumbosacral spine operations were examined. They
      were all treated conservatively with bed rest in the Trendelenburg position,
      antibiotic coverage, watertight skin suturing, and daily subcutaneous punctures.
      No patient was operated on for the same type of complication.

PMID- 2003238
TI  - Anterior perforations in lumbar discectomies. A report of four cases of vascular
      complications and a CT study of the prevertebral lumbar anatomy.
AB  - Four cases of vascular complications to anterior perforations during discectomy
      prompted a CT study to measure lumbar disc diameters and to evaluate the
      prevertebral anatomy. Fifty young adults who had been referred for low-back pain
      and/or sciatica but had not undergone operation were included. In five additional
      patients, prone versus supine CT examinations were compared. Six typical
      configurations of the vascular anatomy could be classified to explain the type of
      vascular complications occurring at the L3-4 and L4-L5 disc levels. The sagittal
      diameter of the three lowest lumbar discs varied from 33 to 56 mm, indicating the
      importance of this parameter as an intraoperative guideline for the spine
      surgeon. Air-filled intestines were observed anterior to the L5-S1 disc
      predominantly in the prone position. The possible relationship between this
      finding and postoperative discitis is discussed.

PMID- 2003239
TI  - Experimental nerve root compression. A model of acute, graded compression of the
      porcine cauda equina and an analysis of neural and vascular anatomy.
AB  - Nerve root compression has been suggested as one important pathogenetic factor in
      low-back pain syndromes and sciatica. The underlying pathophysiologic mechanisms
      are, however, incompletely known, partly because of the lack of experimental data
      on this topic. In the present study, a model for experimental compression of the
      porcine sacrococcygeal cauda equina is presented. The model consists of surgical
      exposure of the cauda equina and compression of the cauda equina toward the
      ventral aspect of the spinal canal by an inflatable balloon fixed to the spine.
      This compression system was shown to have a high accuracy in pressure
      transmission from the balloon to the cauda equina. The gross and microscopic
      neural anatomy and the vascular anatomy of the porcine cauda equina were analyzed
      with light microscopic and ink-perfusion techniques. The porcine cauda equina
      showed a close anatomic resemblance to the human lumbosacral cauda equina. The
      presented model offers unique possibilities for experimental studies on nerve
      root compression injury because of the easy surgical exposure and the sufficient
      length of the nerve roots. In separate studies, this model, along with
      investigations of solute transport to the nerve tissue and of impulse
      propagation, has been used to analyze the effects of acute, graded compression on
      blood flow and edema formation in the cauda equina. The porcine cauda equina
      would also be particularly suitable for chronic compression studies because any
      neurologic deficit acquired would be restricted to the tail.

PMID- 2003240
TI  - Anterior decompression and stabilization of thoracolumbar burst fractures by the
      use of the Slot-Zielke device.
AB  - Between July 1983 and November 1986, 29 patients with thoracolumbar burst
      fractures underwent a one-stage operation consisting of anterior decompression by
      subtotal vertebrectomy, reduction, and stabilization with the Slot-Zielke device.
      The mean follow-up was 3.1 years. Most patients with incomplete neurologic
      lesions showed postoperative improvement and were upgraded one or two steps in
      the Frankel scale. No patient showed neurologic deterioration after surgery. In
      all patients, bony union occurred. Loss of reduction of more than 5 degrees
      occurred in 41% of the patients. Because of this high rate of loss of reduction
      in patients and the low degree of flexion-bending loading and torsional stability
      in biomechanical evaluation in vitro of the Slot-Zielke device on human cadaveric
      spines, an additional posterior stabilization of the spine after an anterior
      approach for anterior- and middle-column fractures should be considered.

PMID- 2003242
TI  - Idiopathic scoliosis and asymmetry of form and function.
AB  - This report investigates dimensions of hand and foot preference in 159 girls with
      idiopathic scoliosis diagnosed after the age of 8 years, 1,522 girls with
      clinically straight spines, and 132 with minor truncal asymmetry. It was found
      that, although there was no significant difference in hand or foot preference for
      individual items between scoliotic groups and controls, there was a statistically
      significant tendency for children with any degree of asymmetry to show uniform
      lateralization in the sense of consistency of side preference. Another, smaller
      group showed a tendency for scoliosis to be associated with clearly visible
      facial asymmetry, which itself correlated with handedness. It was concluded that
      theories of scoliosis need to include the frequently ignored minor observations,
      such as the well-known fact of lateralization of the curve, if they are to
      describe the condition completely. Because the asymmetry of cerebral
      lateralization is known to be genetically determined and because it is thought to
      result in other skeletal asymmetries, such as skull and limb inequality, it
      seemed reasonable to investigate the primary cause of that gross asymmetry,
      idiopathic scoliosis.

PMID- 2003241
TI  - Spinal cord injuries. Clinical, functional, and emotional status.
AB  - Ninety-eight patients with traumatic spinal cord injury, at a median age of 33.5
      years (range, 16-72 years), with nonremarkable distributions of neurologic
      characteristics were investigated at a median of 2.3 years (range, 0.1-23 years)
      after injury. Functioning, mood disturbances, and overall quality of life were
      recorded with established self-assessment instruments. Physical dysfunction
      levels were moderate, being proportionate to neurologic impairment. Psychosocial
      functions, mood states, and quality-of-life perceptions did not differ from those
      of a control population sample. Psychosocial function and mood disturbances
      varied greatly during the first 4 years after injury, but patients' later
      recordings expressed predominantly a balanced emotional state and a rewarding
      social life. Progress in this direction consisted of clearly lessened physical
      dysfunction 1 year after injury and better psychosocial function and well-being
      after 2 years, whereas patterns of social activities and contacts became
      gradually less inhibited during a 4-year period after injury. Analysis of
      complications in patients' histories that affected function and mood showed
      severe pain to be the only complication that related to lower quality-of-life
      scores. Urinary incontinence and infection and autonomous dysreflexia related to
      inhibited self-care performance; spasticity related to impaired ambulation and
      feeding skills. Gainful employment was the only demographic factor linked to high
      quality-of-life scores.

PMID- 2003243
TI  - The effect of an exercise program on vital capacity and rib mobility in patients
      with idiopathic scoliosis.
AB  - All 813 patients with idiopathic scoliosis who completed their first Schroth
      physiotherapeutic rehabilitation program at the Katharina Schroth Hospital
      between 1984 and 1987 were reviewed. The patients were divided into four age
      groups. In Group I (10-13 years, N = 278), vital capacity in patients treated for
      the first time improved by 18.94% (445 ml). In Group II (14-17 years, N = 264),
      the average increase in vital capacity after initial treatment was 16.33% (497
      ml). In Groups III (18-24 years, N = 123) and IV (greater than 24 years, N =
      148), the corresponding increases were 15.11% (501) and 13.77% (394 ml),
      respectively. In the 256 patients receiving repeat treatment, the increases in
      vital capacity in the respective age groups amounted to just more than half those
      in the patients treated for the first time. The average increase in chest
      expansion was more than 20% in all groups at all measuring points. These findings
      show that a course of inpatient treatment by the Schroth method can lead to an
      increase in vital capacity and chest expansion so that, even in adult scoliosis
      patients, effective treatment of the associated restrictive ventilatory disorder
      is possible.

PMID- 2003244
TI  - Respiratory deficiency in experimental idiopathic scoliosis.
AB  - Clinically significant respiratory failure in a group of animals with an
      experimentally produced structural thoracic scoliosis was identified. A detailed
      physiologic investigation of their respiratory function showed that their
      respiratory compromise was associated with the development of a smaller and
      stiffer chest. Frank respiratory failure, however, was rare and seen only in
      animals with the most severe spinal deformities when it was also associated with
      a general failure to thrive. Animals with less severe deformities had little
      measurable restriction of pulmonary function, did not develop respiratory
      failure, and grew normally.

PMID- 2003245
TI  - Inner-city trauma centers. Financial burdens or community saviors?
AB  - Trauma systems have proved effective in reducing morbidity and mortality rates.
      Depending on a center's geographic location and patient mix between penetrating
      and blunt trauma, participation in a system may be a liability or an asset. In
      general, inner-city hospitals tend to see more indigent patients and to have
      sizeable financial losses. At the same time, they provide an invaluable service
      to any community, and their ability to do so must be preserved. The two important
      issues of malpractice and uncompensated care threaten to destroy the very concept
      of trauma care and therefore pose a serious threat to the health care profession.
      Solutions are possible, but it will take a significant public awareness and
      education campaign to elicit the support and initiate the programs that will
      ensure that every injured patient has an opportunity to receive the best of
      trauma care. Inner-city hospitals are both a financial burden and a community
      savior.

PMID- 2003246
TI  - Contemporary problems in trauma surgery.

PMID- 2003247
TI  - Principles of ballistics applicable to the treatment of gunshot wounds.
AB  - Ballistics is the science of the motion of a projectile through the barrel of a
      firearm (internal ballistics), during its subsequent flight (external
      ballistics), and during its final complicated motion after it strikes a target
      (terminal ballistics). Wound ballistics is a special case of terminal ballistics.
      Although wound ballistics is at best sets of approximations, its principles enter
      usefully into an evaluation of a gunshot wound and its treatment. A special
      consideration in these cases is their medicolegal aspects. At a minimum, the
      medical team receiving the patient should exert care not to destroy the clothing
      and in particular to cut around and not through bullet holes, to turn over to law
      enforcement officials any metallic foreign body recovered from the patient, and
      to describe precisely, or even to photograph, any entrance or exit wounds.

PMID- 2003248
TI  - Diagnostic modalities in abdominal trauma. Peritoneal lavage, ultrasonography,
      computed tomography scanning, and arteriography.
AB  - Numerous algorithms encompassing the diagnostic studies described above have been
      published in recent years. For practical purposes, diagnostic peritoneal lavage
      and CT scanning are the diagnostic studies most commonly used in patients without
      obvious indications for celiotomy after blunt or penetrating abdominal trauma.
      Diagnostic peritoneal lavage is invasive, rapidly performed, cheap, and accurate
      and has a primary role in documenting intra-abdominal bleeding or contamination
      in hypotensive patients with blunt trauma or selected stable patients with
      penetrating stab wounds. It misses small and large injuries to the diaphragm and
      cannot rule out injury to retroperitoneal structures. Computed tomography is
      noninvasive, time consuming to perform, expensive, and accurate and has a primary
      role in defining the location and magnitude of intra-abdominal injuries in stable
      patients with blunt trauma or with penetrating trauma to the flank or back. In
      many hospitals, it misses gastrointestinal perforations or ruptures. Both studies
      may be needed in the same stable patient, and both should be available and used
      in a complementary fashion in the modern trauma center.

PMID- 2003249
TI  - Disaster management. Lessons learned.
AB  - Our experiences have taught us that practice makes perfect and that it probably
      is unreasonable to expect everything to be orderly, sane, and appropriate during
      disaster management. The best we can hope for probably is controlled chaos. We do
      believe that we have generated an improved plan, that the plan is known, and that
      it is being revised continuously. We can no longer rely on our goodwill and good
      intentions to manage mass casualties in a disaster. There are too many factors
      that can reduce our ability to provide medical care in this situation. Hospital
      planning is essential. The hospital should be represented on the emergency
      preparedness committee so it is knowledgeable about the various plans throughout
      the city. Each plan must be practiced and critiqued to identify potential
      problems. Hospital staff must be kept current on the various plans to understand
      the communication, authority, responsibility, security, and medical control for
      each plan. We have instituted a video program outlining the various tasks for
      each hospital department for each disaster plan. This format allows the personnel
      in these departments to review their responsibilities continually in a concise
      manner and allows practice of disaster preparedness without implementing an
      entire disaster drill. Table 1 provides a quick review of the areas and questions
      we found to be problems when implementing our disaster plan.

PMID- 2003250
TI  - Management of penetrating neck injuries. The controversy surrounding zone II
      injuries.
AB  - Penetrating neck injuries present a difficult challenge in management, given the
      unique anatomy of the neck. Controversy surrounds the approach to zone II
      injuries; mandatory versus selective exploration. On the basis of an extensive
      literature review, the authors conclude that neither approach is obviously
      superior. A selective approach is safe in the asymptomatic and hemodynamically
      stable patient, provided that accurate invasive diagnostic means are immediately
      available. The mandatory approach is safe, reliable, and time tested. The
      greatest problem appears to be the accuracy of detection of cervical esophageal
      injuries: Radiologic evaluation may be inaccurate, rigid esophagoscopy carries a
      risk of perforation, and the injury may easily be overlooked during surgical
      exploration.

PMID- 2003251
TI  - Penetrating orthopedic injuries.
AB  - The treatment of gunshot wounds involving bones or joints remains controversial.
      Antibiotics and thorough debridement may not be necessary for many of these
      wounds (stable fractures with minimal soft-tissue damage). However, as in the
      treatment of open fractures and joint injuries from blunt trauma, the damage to
      the skin frequently is not a good indicator of the amount of soft tissue to be
      found underneath.

PMID- 2003252
TI  - Penetrating craniocerebral trauma.
AB  - The authors review the pathophysiology of penetrating and perforating cranial
      wounds. Radiologic evaluation includes computed tomography and angiography.
      Operative technique and perioperative critical care are discussed, with special
      emphasis on the control of the intracranial pressure. Other problems such as
      fluid and electrolyte disorders and nutrition are discussed in relation to
      neurosurgery.

PMID- 2003253
TI  - Extremity replantation.
AB  - Although the success of replantation and revascularization is in part related to
      the length of the ischemic interval, it is important to bear in mind that
      microsurgical intervention must be given appropriate priority relative to the
      patient's other injuries. Very few patients die as a result of upper extremity
      trauma. However, the economic, psychologic, and physical debility of a chronic
      hand injury will be the ultimate handicap in patients who survive multisystem
      trauma. Therefore, management of the injured extremity has an important place in
      the overall scheme of trauma care.

PMID- 2003254
TI  - Vertical deceleration trauma. Principles of management.
AB  - A highly complex interaction of several physical and biomechanical factors
      determines the patterns of injury and probability of survival in free falls.
      Falls from extreme heights result in massive visceral and vascular injuries,
      which are usually lethal. Urban falls tend to result in severe lower extremity,
      spinal, and pelvic fractures. Retroperitoneal hemorrhage is a significant cause
      of death and is best managed by emergency angiography and embolization. Early
      fixation of fractures reduces morbidity.

PMID- 2003255
TI  - New horizons in management of hypothermia and frostbite injury.
AB  - Diagnosing hypothermia requires a high index of suspicion. Restoring lost heat
      with careful attention to hemodynamics usually results in complete recovery.
      Frostbite is best treated by physicians who are cognizant of the pathophysiology
      of cold injury. Although alternative methods of intervention are being tested,
      rapid rewarming and anti-inflammatory agents are integral to treatment protocols.

PMID- 2003256
TI  - Soft-tissue infections after trauma.
AB  - Soft-tissue infections are best prevented by proper initial management of the
      wound. When they do occur, they produce certain characteristic physical signs,
      the appearance of which mandates prompt operative intervention. The extent of
      debridement is determined by the intraoperative findings. Diagnostic
      categorization of the infection is performed postoperatively on the basis of the
      level of soft-tissue involvement and the results of bacterial cultures.

PMID- 2003257
TI  - Inhalation injuries and burns in the inner city.
AB  - Burns in the urban environment present special problems. Although there generally
      is ready access to appropriate care and short transport times, burn injury
      remains a serious concern. Inhalation injuries, electrical and chemical burns,
      and burns as a result of abuse or assault are common problems.

PMID- 2003258
TI  - Missed injuries. The trauma surgeon's nemesis.
AB  - The multiply injured trauma patient presents a diagnostic and therapeutic
      challenge: that of discovering all injuries while simultaneously proceeding with
      resuscitation and maintaining life. Many factors involved in the initial
      resuscitation of the multiply injured patient, such as altered level of
      consciousness, hemodynamic instability, or inexperience and diagnostic oversight,
      may lead to missed injuries. Injuries may be missed at any stage of the
      management of the trauma patient, including intraoperatively, and may involve all
      regions of the body. Established protocols in the initial management of the
      multiply injured patient, such as the primary and secondary surveys of the
      Advanced Trauma Life Support Course, will minimize the chance of missing
      immediately life-threatening injuries in the emergency department. A careful
      intraoperative approach must be used in all patients, but especially in those
      with hemodynamic instability, so that all areas are examined for possible injury,
      rather than concentrating simply on what is known to be injured. Use of the
      tertiary survey, a careful re-examination of the multiply injured trauma patient,
      especially when he or she awakes, will help detect injuries missed during the
      initial evaluation. Injuries will be missed. Rather than dismissing these as
      occurrences that happen only to the inexperienced or incompetent, one should
      approach the multiply injured trauma patient with both special alertness and the
      humility necessary to search for diagnostic oversights. This approach will lead
      to early discovery of missed injuries and will minimize the consequences.

PMID- 2003259
TI  - Nautical accidents. Unique injuries.
AB  - Not much has been written about nautical injuries, although the increasingly
      popular recreational boating activities and other water sports are becoming a
      significant source of injury and death. The authors review common and not-so
      common nautical injuries and possible preventive measures.

PMID- 2003260
TI  - [Stomach dilatation-volvulus in the dog: current viewpoint and retrospective
      study in 160 patients].
AB  - Diagnosis and treatment of gastric dilatation-volvulus syndrome in the dog are
      described. A comparison of results obtained between 1984 and 1990 with results
      from 1977 to 1982 shows a significant decrease in mortality from 63% to 29%, and
      in the recurrence rate from 82% to 15%. Mortality in patients in which the
      stomach was decompressed before referral did not differ from that in patients in
      which decompression was not performed. Two methods of fixation of the pyloric
      antrum to the abdominal wall are compared. Complications and recurrence rates
      after tube gastrostomy do not differ significantly from those after gastropexy.
      The common opinion that dilatation precedes volvulus is rejected. A new
      hypothesis is proposed, in which volvulus precedes dilatation.

PMID- 2003261
TI  - [Roentgen diagnosis of stomach volvulus].
AB  - In this article, the radiographic examination and presentation of dogs with
      gastric dilatation-volvulus syndrome is discussed. Much emphasis is placed on the
      influence of gravitational positioning on the detection of the abnormality. A
      list of radiographic signs is included.

PMID- 2003262
TI  - [Anesthesia in the patient with stomach dilatation-volvulus].
AB  - Before a decision on the anesthetic protocol and the various patient support
      measures can be taken, the pathophysiological changes that occur during a gastric
      dilatation-volvulus need to be evaluated. The most important changes are of a
      circulatory and/or respiratory nature, inducing hypotension, hypovolaemia,
      cardiac dysrhythmias, a decreased respiratory minute volume, and subsequently
      resulting in changes in the acid-base balance and plasma electrolyte
      concentration. In view of these changes and the increased anaesthetic risk for
      the patient with gastric dilatation-volvulus, the use of barbiturates or ketamine
      cannot be recommended for anaesthetising these patients. With the use of
      neurolept-analgesic combinations, such as methadone-droperidol or sufentanil
      midazolam, an increased cardiovascular stability and an ample analgesic effect
      can be obtained. Especially with the potent sufentanil in combination with
      midazolam, an excellent anaesthesia for patients with gastric dilatation-volvulus
      can be achieved.

PMID- 2003263
TI  - [Pyloric stenosis in the dog: developments in its surgical treatment and
      retrospective study in 47 patients].
AB  - Diagnosis and treatment of pyloric stenosis in the dog are described. The most
      common causes in 47 dogs were hypertrophic and functional pyloric stenosis. These
      conditions were mostly seen in young, male dogs of brachycephalic breeds. In
      contrast with the literature no indications were found for a predisposition in
      miniature breeds. Hypertrophic stenosis was treated successfully with the Fredet
      Ramstedt pyloromyotomy. Functional stenosis and hypertrophic gastritis were
      mainly treated with the Heineke-Mikulicz pyloroplasty; good results were obtained
      in more than half of the cases.

PMID- 2003264
TI  - [Perineal hernia in the dog: developments in its treatment and retrospective
      study in 197 patients].
AB  - Perineal hernia repair by transposition of the internal obturator muscle and the
      results obtained with this method in 197 dogs are described. The most common
      breeds were the German shepherd, the Bouvier and the old English sheepdog, all of
      which were significantly over-represented when compared with the hospital
      population. A comparison of results obtained before 1982 with those from the
      period between 1985 and 1990 shows a significant decrease of the recurrence rate
      from 43% to 21%. There was no change in the percentage of patients with fecal
      incontinence. Wound infections occurred in 22% of the patients and were the most
      important complication. This implies a reduction of 50% compared with an earlier
      study of 100 patients. Eighty per cent of the owners classified the results of
      treatment as excellent or good. This is in accordance with results obtained in
      the United States with a similar method. The omittance of castration in dogs in
      which the prostate was of normal size did not result in an increased risk of
      recurrence and is considered to be justified.

PMID- 2003265
TI  - [BST (bovine somatotropin)].

PMID- 2003266
TI  - Distribution and metabolism of insect repellant N,N-diethylphenylacetamide on
      oral exposure in rats.
AB  - Oral toxicity, distribution and metabolism of a new multi-insect repellant, N,N
      diethylphenylacetamide (DEPA) was studied in rats. On administration of DEPA (851
      mg/kg body wt.) labelled with 14C blood, liver, stomach and stomach contents had
      2.65, 3.97, 12.07 and greater than 50.66% radioactivity, respectively, after 20
      min. Gas chromatographic analysis showed presence of both DEPA and its metabolite
      N-ethylphenylacetamide (EPA) in blood, liver, kidneys and lungs while only DEPA
      was present in stomach and stomach contents. EPA, phenylacetamide and conjugated
      phenylacetic acid were excreted along with unmetabolized parent compound in urine
      of rats when a low oral dose of DEPA (70 mg/kg body wt.) was administered.
      Activities of erythrocyte cholinesterase and carbonic anhydrase did not change
      significantly upon acute oral exposure to DEPA.

PMID- 2003267
TI  - Induction of hepatic peroxisomes by a new, non-carboxylate-containing drug,
      bifonazole.
AB  - The acute effect of an antimycotic drug, bifonazole, on hepatic peroxisomes of
      rats was studied in comparison with that of clotrimazole, which has a similar
      structure. By feeding 0.5% bifonazole in the diet for 5 days, the activities of
      carnitine acyltransferase, carnitine palmitoyltransferase and the peroxisomal
      beta-oxidation system were increased by 30-, 3- and 7-fold, respectively, over
      the control. Under the same conditions, clotrimazole did not cause such changes.
      Electron microscopic observation showed that peroxisome proliferation had been
      induced by bifonazole treatment. Thus, a compound which does not contain a
      carboxylate moiety can induce peroxisomes in rodent liver.

PMID- 2003268
TI  - Interaction between cadmium and copper on ossification of embryonic chick bone in
      tissue culture.
AB  - To investigate the interaction between cadmium and copper in ossification, femurs
      from 9-day-old chick embryos were cultured for 6 days in the presence of 2 microM
      cadmium and/or 1 microM copper. It was found that cadmium + copper treatment
      caused interactively severe damage to osteogenic mesenchymal cells in the
      periosteum and a severe degenerative change in osteoblasts around the trabecula,
      resulting in severe impairment of ossification in the diaphysis. Cadmium content
      was increased by copper; however, copper content was unaffected by cadmium in the
      diaphysis. It was therefore considered that the copper-induced increase in
      cadmium content was a primary factor in the interactive toxic effect of the
      cadmium + copper treatment in ossification.

PMID- 2003269
TI  - Studies of the teratogenicity of xanthomegnin and viridicatumtoxin in ICR mice.
AB  - The myotoxins xanthomegnin and viridicatumtoxin were not teratogenic when
      administered orally to pregnant ICR mice during the 8-12th and 8-13th days of
      gestation, respectively. Viridicatumtoxin produced high mortality in mice given
      200, 250 or 350 mg/kg of body weight.

PMID- 2003270
TI  - Combined effects of methylmercury and ethanol on renal metallothionein and
      mercury residues in rats fed restricted amounts of a liquid diet.
AB  - Simultaneous treatment of rats with ethanol (EtOH) and methylmercury (MeHg)
      increases the frequency of lesions in the rat kidney. Therefore, it was of
      interest to us to study the effects of simultaneous treatment of rats with MeHg
      and EtOH on kidney metallothionein (MT) and mercury residues levels in kidneys of
      rats maintained on 70% of ad libitum diet. Treatment with MeHg alone induced
      kidney MT the most (twice) compared to its pair-fed control. Simultaneous
      treatment with MeHg and EtOH also induced kidney MT but to a lesser degree than
      treatment with MeHg alone (by about 30%). Ethanol by itself caused a slight
      increase in kidney MT although starvation resulting from pair-feeding with
      mercury-treated animals may have contributed to this observation. Simultaneous
      treatment with MeHg and 2 g/kg EtOH caused a significant reduction in inorganic
      mercury levels in the kidney (P less than 0.05) compared to treatment with MeHg
      alone or in combination with 1 g/kg EtOH. Corresponding with the decrease in
      kidney inorganic mercury levels was a significant increase in urine inorganic
      mercury levels in this group compared to treatment with 1 g/kg ethanol + MeHg.

PMID- 2003271
TI  - Hepatotoxicity of DR-3438, tienilic acid, indacrinone and furosemide studied in
      vitro.
AB  - A new diuretic antihypertensive, DR-3438, and marketed diuretic drugs were
      evaluated for their toxicity in vitro. Hepatocytes were isolated from male rats
      by the collagenase perfusion method and incubated in Dulbecco's modified Eagle
      medium containing various doses of DR-3438, tienilic acid, indacrinone or
      furosemide. Tienilic acid decreased cell viability and glutathione content in
      hepatocytes and increased lipid peroxidation in the cells. Indacrinone also
      decreased cell viability, but neither cell viability nor glutathione content was
      affected by furosemide or DR-3438.

PMID- 2003272
TI  - A personal diffusive sampler for occupational acetone vapor exposure monitoring.
AB  - A commercially produced badge-type personal sampler, with water as absorbent and
      originally designed for monitoring of formaldehyde, was investigated for possible
      application to monitoring of occupational exposure to acetone, one of the
      hydrophilic solvents which cannot be monitored so far with activated carbon cloth
      equipped diffusive samplers. Under the experimental condition of exposure at
      constant acetone concentration, the amount of acetone absorbed was proportional
      to the acetone exposure concentration up to 1500 ppm and duration of exposure for
      up to 8 h. Inter-sampler variation became wider, however, at 8 h of exposure to
      1500 ppm acetone. Loss of acetone in the absorbent water due to spontaneous
      desorption became significant at 6 h after acetone impregnation of absorbent
      water. In practice, therefore, limitation of the duration of exposure up to 4 h
      is recommended.

PMID- 2003273
TI  - Significant increase of urinary mucoprotein in environmental-cadmium-exposed
      Japanese subjects.
AB  - Urinary mucoprotein (U-MP) was determined in 169 Japanese environmental-cadmium
      exposed and 81 non-exposed subjects. Urinary total protein, albumin, beta 2
      microglobulin (beta 2-MG), cadmium (Cd) and creatinine were also measured.
      Significant increases in U-MP and other proteins were found in the Cd-exposed
      subjects. Significant correlations between each protein were seen in the Cd
      exposed and the total group of subjects. U-MP was highly correlated with urinary
      beta 2-MG and their correlation coefficient was the highest in the total group of
      subjects. beta 2-MG was the most sensitive indicator among them to detect Cd
      induced renal dysfunction, although beta 2-MG is degraded in urine with a pH less
      than 5.5 U-MP is an acid-soluble protein. Therefore, U-MP is also available for
      studies on renal dysfunction caused by exposure to Cd, in conjunction with beta 2
      MG.

PMID- 2003274
TI  - Sister chromatid exchanges in lymphocytes of nurses handling antineoplastic
      drugs.
AB  - The effects of handling antineoplastic drugs were examined in a group of 23
      nurses working in the hematology and oncology departments of different university
      hospitals in Ankara and in a group of 50 unexposed controls. The cytogenetic
      repercussions of exposure were assessed by examining sister chromatid exchanges
      (SCEs) in circulating lymphocytes which result from the breakage and rejoining of
      DNA at apparently homologous sites on the 2 chromatids of a single chromosome. A
      significant increased frequency of SCE is observed in nurses in daily contact
      with antineoplastics (n = 23, mean SCEs/cell +/- SE 6.5 +/- 0.2) as compared to a
      group of controls (n = 50, mean SCEs/cell 5.2 +/- 0.2). The nurses who smoked
      also had a higher SCE frequency (n = 15, mean SCEs/cell 7.0 +/- 0.3) than non
      smokers, (n = 8, mean SCEs/cell 5.5 +/- 0.3). A significant increase (P less than
      0.001) in the mean number of SCE was found for non-smoking nurses as compared to
      non-smoking controls (n = 27, mean SCEs/cell 4.1 +/- 0.2).

PMID- 2003275
TI  - Evaluation of compounds as barriers to dermal penetration of organophosphates
      using acetylcholinesterase inhibition.
AB  - An efficient, objective method for evaluating the efficacy of barrier compounds
      in preventing dermal penetration of organophosphates (OP) in rabbits was
      developed using time-dependent reduction in erythrocyte (RBC)
      acetylcholinesterase (AChE) activity as an endpoint. Anesthetized rabbits, with
      or without a dermal application of a mixture of high- and low-molecular-weight
      polyethylene glycols (mean molecular weight of 540 daltons; PEG 540), were
      exposed to different percutaneous doses of 3 highly toxic OP compounds. Dose
      response curves were generated for RBC AChE inhibition as a function of
      percutaneous dose for each OP test material over time. From data generated, a
      single dose of each OP was selected to challenge PEG-540-protected and
      unprotected animals to validate the method as a means of differentiating
      effective from ineffective barriers to skin penetration. Data for a complete
      evaluation of a PEG 540 test barrier application were obtained within 4 h and
      anesthesia was maintained for the entire period.

PMID- 2003276
TI  - Inhibition of acetylcholinesterase by caffeine, anabasine, methyl pyrrolidine and
      their derivatives.
AB  - The inhibition of acetylcholinesterase (AChE) by caffeine, anabasine,
      methylpyrrolidine and several derivatives was examined. Most of the compounds had
      moderate inhibitory activity with I50 values in the range of 87-480 microM. The
      inhibition of AChE by these compounds has not been previously reported. A
      structural feature common to these compounds is the N-methyl determinant of the
      pyrrolidine ring which may be important in binding to the AChE.

PMID- 2003277
TI  - The effects of trinitrotoluene toxicity on zinc and copper metabolism.
AB  - Wistar rats were exposed to trinitrotoluene (TNT, 200 mg/kg/d x 6 d/wk) for 6
      weeks, and a 2-week recovery period was continued after treatment. After
      initiation of TNT exposure, zinc and copper concentrations in rat testes, liver
      and serum, and serum caeruloplasmin activity were assayed every 2 weeks.
      Testicular size and zinc concentrations were decreased throughout the exposure
      and recovery periods. After 6 weeks of TNT exposure, rat testicular copper and
      serum zinc concentrations were significantly decreased and increased,
      respectively. The activities of caeruloplasmin were decreased after 4 and 6 weeks
      of exposure. Liver zinc and copper concentrations and serum copper concentrations
      had not changed significantly in rats throughout the exposure and recovery
      periods. Copper concentration in hair samples from TNT-exposed workers was lower
      than that in control workers, but zinc content was significantly increased
      compared with that in control workers.

PMID- 2003278
TI  - Stroke recurrence within 2 years after ischemic infarction.
AB  - We prospectively studied stroke recurrence in 1,273 patients with ischemic stroke
      who were entered into the Stroke Data Bank. Median follow-up was 13 months. The 2
      year cumulative recurrence rate among these patients was 14.1%. Age, sex, race,
      history of hypertension, atrial fibrillation, or transient ischemic attacks, and
      stroke location were not associated with a higher risk of stroke recurrence.
      Patients with an elevated blood pressure, an abnormal initial computed tomogram,
      or a history of diabetes mellitus were at a higher risk of stroke recurrence. In
      contrast, patients with an infarct of unknown cause were at a lower risk of
      stroke recurrence than patients with a defined stroke mechanism, such as lacune,
      embolism, or atherosclerosis. A multivariate model suggests that patients at the
      lowest risk for stroke recurrence have a low diastolic blood pressure, no history
      of stroke, no history of diabetes mellitus, and an infarct of unknown cause.

PMID- 2003279
TI  - Chronic blood hyperviscosity in subjects with acute stroke, transient ischemic
      attack, and risk factors for stroke.
AB  - The origin and significance of blood hyperviscosity in subjects with acute stroke
      has been controversial. It has been argued that viscous abnormalities simply
      reflect either elevated hematocrit or an acute-phase response to the stroke
      itself. To address these issues, we measured the factors that determine blood
      viscosity in a cross-sectional study of 430 subjects, including 135 with acute
      stroke, 89 with acute transient ischemic attacks of the brain, 115 with
      recognized risk factors for stroke, and 91 healthy controls. The at-risk group
      was balanced with the acute stroke group for types of risk factors and medication
      usage, and all four groups were balanced for age. The viscosity of whole blood at
      low rates of shear and the plasma viscosity were significantly elevated in both
      groups with cerebrovascular symptoms and in the at-risk group compared with the
      healthy controls. The severity of hyperviscosity was stroke group greater than
      transient ischemic attack group greater than at-risk group greater than healthy
      controls. Increased viscosity of whole blood was associated with an elevated
      plasma fibrinogen concentration and with a decreased albumin/globulin ratio. This
      study provides evidence that blood hyperviscosity is present not only in subjects
      with acute brain infarction, but also in those with risk factors for stroke, and
      that these abnormalities are, to a considerable degree, chronic.

PMID- 2003280
TI  - Mortality in acute stroke with atrial fibrillation. The Italian Acute Stroke
      Study Group.
AB  - We compared 211 consecutive patients who had acute ischemic hemispheric stroke
      and atrial fibrillation with 837 consecutive patients who had stroke without
      atrial fibrillation. The atrial fibrillation group included a higher frequency of
      women, older subjects, and those with a severe neurologic deficit, abnormal
      computed tomogram, and elevated heart rate. The 1-month case-fatality rate in the
      atrial fibrillation group was 27% while that in the group without atrial
      fibrillation was 14%. The 6-month case-fatality rates in the two groups were 40%
      and 20%, respectively. The risk of death attributable to atrial fibrillation,
      adjusted for the effect of other prognostic factors, was significant at 1 month
      (relative risk = 1.55) and at 6 months (relative risk = 1.74). The causes of
      death were equally distributed in the two groups during both the acute and
      subacute phases. We conclude that atrial fibrillation is a negative prognostic
      factor in patients hospitalized for acute stroke. Nevertheless, cerebral embolism
      alone does not completely explain the increase in mortality for stroke patients
      with atrial fibrillation. Other associated pathogenetic mechanisms must also be
      taken into account.

PMID- 2003281
TI  - Clinical-computed tomographic correlations of lacunar infarction in the Stroke
      Data Bank.
AB  - Lacunar stroke was diagnosed in 337 (26%) of the 1,273 patients with cerebral
      infarction among the 1,805 total in the Stroke Data Bank. We analyzed the 316
      patients with classic lacunar syndromes. Among these, 181 (57%) had pure motor
      hemiparesis, 63 (20%) sensorimotor syndrome, 33 (10%) ataxic hemiparesis, 21 (7%)
      pure sensory syndrome, and 18 (6%) dysarthria-clumsy hand syndrome. No striking
      differences were found among the risk factors for the lacunar subtypes, but
      differences were found between lacunar stroke as a group and other types of
      infarcts. Compared to 113 patients with large-vessel atherosclerotic infarction,
      those with lacunar stroke had fewer previous transient ischemic attacks and
      strokes. Compared to 246 with cardioembolic infarction, patients with lacunar
      stroke more frequently had hypertension and diabetes and less frequently had
      cardiac disease. We found a lesion in 35% of the lacunar stroke patients'
      computed tomograms, with most lesions located in the internal capsule and corona
      radiata. The mean infarct volume was greater in patients with pure motor
      hemiparesis or sensorimotor syndrome than in those with the other lacunar stroke
      subtypes. In patients with pure motor hemiparesis and infarcts in the posterior
      limb of the internal capsule, there was a correlation between lesion volume and
      hemiparesis severity except for the few whose infarct involved the lowest portion
      of the internal capsule; in these patients severe deficits occurred regardless of
      lesion volume. Taken together, the computed tomographic correlations with the
      syndromes of hemiparesis showed only slight support for the classical view of a
      homunculus in the internal capsule.

PMID- 2003282
TI  - Treatment of acute hydrocephalus after subarachnoid hemorrhage with serial lumbar
      puncture.
AB  - Computed tomography demonstrated acute hydrocephalus less than or equal to 72
      hours after subarachnoid hemorrhage in 24 (23%) of 104 patients. Of these 24
      patients, six (25%) had no impairment of consciousness. In nine (11%) of the
      remaining 80 patients, acute hydrocephalus developed within 1 week after
      subarachnoid hemorrhage. With the exception of three patients, all 104 patients
      received antifibrinolytic treatment. Delayed clinical deterioration from acute
      hydrocephalus occurred in seven (29%) of the 24 patients with acute hydrocephalus
      on admission and in six (8%) of the remaining 80 patients. Serial lumbar puncture
      was performed in 17 patients. Twelve (71%) of the 17 patients treated with serial
      lumbar puncture, including 10 (77%) of the 13 patients with delayed deterioration
      from acute hydrocephalus after admission, achieved improvement in the level of
      consciousness. Four of these 17 patients (4% of all 104 patients) required an
      internal shunt. No patient deteriorated from coning following serial lumbar
      puncture. The rebleeding rate within 12 days after subarachnoid hemorrhage in
      hydrocephalic patients with serial lumbar puncture was not higher than the rate
      in those without hydrocephalus (two [12%] of 17 versus nine [13%] of 71). Neither
      meningitis nor ventriculitis was observed. We conclude that if neither a hematoma
      with a mass effect nor an obstructive element exists, cerebrospinal fluid
      drainage with serial lumbar puncture is a good alternative to ventricular
      drainage in patients with acute hydrocephalus after subarachnoid hemorrhage.

PMID- 2003283
TI  - Brain magnetic resonance imaging and neuropsychologic evaluation of patients with
      idiopathic dilated cardiomyopathy.
AB  - We compared brain magnetic resonance imaging and neuropsychologic performance in
      20 neurologically asymptomatic patients suffering from idiopathic dilated
      cardiomyopathy (mean age 41 [range 18-49] years) and 20 age-matched controls
      (mean age 38 [range 28-49] years). Patients exhibited a significantly higher rate
      of cerebral infarcts (20% versus 0%, p less than 0.05) and cortical (50% versus
      5%, p less than 0.01) and ventricular (55% versus 15%, p less than 0.02) atrophy
      than controls. Accordingly, semiquantitative volumetric measurements yielded a
      significantly increased ventricular-to-intracranial cavity ratio in the patients
      (6.2 +/- 2.9% versus 4.1 +/- 1.3%, p less than 0.01). This ratio and the cortical
      atrophy ratings correlated positively with disease duration (r = 0.63 and 0.54, p
      less than 0.05). Cognitive test performance was significantly worse in patients
      than in controls and was most impaired in those patients with morphologic
      cerebral abnormalities.

PMID- 2003284
TI  - Prognostic significance of conjugate eye deviation in stroke patients.
AB  - We prospectively studied the prognostic significance of conjugate eye deviation
      in 80 patients with acute stroke and compared the 3-month mortality and
      disability of these patients to those of the Tilburg epidemiological study of
      stroke. Mortality of patients with conjugate eye deviation was higher (41%) than
      for the general stroke population (34%), but this difference was not
      statistically significant (p less than 0.179). Looking at mortality and
      disability together, we found the outcome of patients with conjugate eye
      deviation to be significantly worse (p less than 0.001). Deviation of the eyes
      occurred more frequently to the right (65%) than to the left (35%). In the
      patient group with eye deviation to the left, mortality was significantly higher
      (64%, p less than 0.001) than in the group with eye deviation to the right (25%);
      only two patients of the former group (n = 28) could return home. Compared to the
      Tilburg epidemiological study of stroke, the group with eye deviation to the left
      did significantly worse, both for mortality alone (p less than 0.001) and for
      mortality and disability together (p less than 0.001). The group with eye
      deviation to the right did significantly worse only for mortality and disability
      together (p less than 0.01). Our results indicate that conjugate eye deviation is
      a prognostic factor for poor short-term mortality and disability in stroke
      patients, especially when the eyes are deviated to the left.

PMID- 2003285
TI  - Atrial fibrillation after stroke in the elderly.
AB  - To examine the relationship between atrial fibrillation and mortality after
      stroke, we studied 186 men and 167 women from the Waikato Stroke Registry whose
      mean age was 75.2 +/- 7.5 years. Twenty-three percent (82 of 353) had atrial
      fibrillation or flutter on their admission electrocardiogram. This group differed
      significantly from that with sinus rhythm in three respects: 1) They were older
      (p less than 0.01); 2) they had more severe current stroke deficit as evidenced
      by lower limb power (p less than 0.05) and Mini-Mental State Score (p less than
      0.001), higher incidence of homonomous hemianopia (p less than 0.05), and lower
      incidence of lacunar syndrome stroke (p less than 0.001); and 3) they had a
      significantly higher incidence of cardiomegaly and congestive heart failure (p
      less than 0.01). Functional outcome was insignificantly better in the group with
      sinus rhythm. During a mean follow-up period of 18 months, mortality was
      significantly higher in the group with atrial fibrillation (p = 0.001).
      Proportional hazards modeling, however, showed that the apparently poorer
      survival in those patients with atrial fibrillation could be explained by factors
      other than cardiac rhythm, such as age, Mini-Mental State Score, level of
      consciousness, and interstitial edema on admission chest radiograph. Thus, atrial
      fibrillation was not an independent predictor of survival after stroke.

PMID- 2003286
TI  - Cromakalim dilates rat cerebral arteries in vitro.
AB  - Using an in vitro perfusion method, we examined the effects of cromakalim, a
      potassium channel opener, on the superior cerebellar arteries of 24 rats.
      Cromakalim had no effect on contractions induced by 129 mM K+ until a
      concentration of 10(-5) M was reached. Contractions evoked by 10(-5) M serotonin
      were attenuated by cromakalim in a concentration-dependent manner (p less than
      0.05). The diameter of untreated superior cerebellar arteries remained almost
      constant with increasing perfusion pressure. However, in the presence of
      cromakalim vessel diameter increased with increasing perfusion pressure. At
      concentrations of 3 x 10(-6) M, cromakalim also inhibited basal myogenic tone and
      dilated unstimulated arteries (p less than 0.01). These results suggest that
      cromakalim is a cerebrovascular dilator acting on both receptor-mediated and
      myogenic contractions.

PMID- 2003287
TI  - Sodium, ATP, and intracellular pH transients during reversible complete ischemia
      of dog cerebrum.
AB  - We tested the hypotheses that with the onset of cerebral ischemia, massive
      cellular sodium influx does not occur until adenosine triphosphate is fully
      depleted and that on reperfusion, neuronal sodium efflux does not occur until
      adenosine triphosphate is fully restored. We examined the temporal relationships
      among transcellular sodium, energy metabolism, and intracellular pH with sodium
      and phosphorus magnetic resonance spectroscopy in a new, hemodynamically stable,
      brain stem-sparing model of reversible, complete cerebral ischemia in eight
      anesthetized dogs. Inflation of a neck tourniquet after placement of glue at the
      tip of the basilar artery resulted in decreased blood flow to the cerebrum from
      29 +/- 5 to 0.3 +/- 0.5 ml/min/100 g. Medullary blood flow was not significantly
      affected, and arterial blood pressure was unchanged. Sodium signal intensity
      decreased and did not lag behind the fall in adenosine triphosphate. After 12
      minutes of ischemia, reperfusion resulted in a more rapid recovery of sodium
      intensity (12.4 +/- 4.8 minutes) than either adenosine triphosphate (16.5 +/- 3.7
      minutes) or intracellular pH (38.9 +/- 1.8 minutes). Because intracellular sodium
      has a weaker signal than extracellular sodium, the decreased sodium intensity is
      interpreted as sodium influx and indicates that sodium influx does not require
      full depletion of adenosine triphosphate. Rapid recovery of sodium intensity
      during early reperfusion may represent sodium efflux, although increased plasma
      volume and sodium uptake from plasma may also contribute. If our interpretation
      of the sodium signal is correct, delayed recovery of adenosine triphosphate may
      be due to the utilization of adenosine triphosphate for the restoration of
      transcellular sodium gradient.

PMID- 2003289
TI  - Basilar artery occlusion in rats.
AB  - The basilar artery is one of the three major sources of blood supply to the
      circle of Willis. To investigate the effects of basilar artery occlusion, we
      surgically exposed and coagulated the basilar artery in 25 rats. Basilar artery
      occlusion at any single point between the foramen magnum and the circle of Willis
      in 11 rats did not produce histologically detectable infarcts in the brain at 12
      24 hours. Two-point occlusions of the basilar artery in 12 rats produced variable
      infarcts between the occlusion sites but no ischemic lesions elsewhere. After
      either single- or double-point occlusions, the proximal basilar artery refilled
      within 2-3 minutes. When the basilar artery was occluded above and below the
      origins of the anterior inferior cerebellar arteries, the artery segments between
      the occlusion points initially collapsed but refilled within 2-3 minutes in two
      rats. Basilar artery occlusions invariably suppressed cortical somatosensory
      evoked potentials by greater than 50%. Regardless of whether a brain stem infarct
      developed, somatosensory evoked potential amplitudes recovered to greater than
      baseline levels by 4 hours in seven of 17 rats and returned to baseline levels by
      24 hours in every rat tested. We conclude that the occluded basilar artery
      receives extensive retrograde collateral blood flow and that somatosensory evoked
      potentials are exquisitely sensitive to basilar artery occlusion but are
      insensitive to whether brain stem infarcts develop.

PMID- 2003288
TI  - Clentiazem reduces infarct size in rabbit middle cerebral artery occlusion.
AB  - We assessed the value of pretreatment with clentiazem (8-chlorodiltiazem), a
      diltiazem derivative with cerebroselective properties, on the consequences of
      surgical occlusion of the middle cerebral artery via a transorbital approach in
      38 rabbits. Nineteen rabbits received 1.7 (n = 5), 5 (n = 8), or 15 (n = 6) mg/kg
      clentiazem orally four times a day for 24 hours before and 48 hours after
      occlusion. Upon sacrifice, a segment of the right middle cerebral artery distal
      to the occlusion and a corresponding segment from the nonoccluded left middle
      cerebral artery were mounted on myographs for in vitro study of their reactivity
      to histamine, acetylcholine, serotonin, norepinephrine, and electrical
      stimulation of intramural sympathetic nerves. Morphometric measurements of 2,3,5
      triphenyltetrazolium chloride-stained brain slices permitted us to estimate
      infarct volume. Pretreatment with 1.7, 5, and 15 mg/kg clentiazem significantly
      reduced infarct volume (p less than 0.05, p less than 0.01, and p less than 0.01,
      respectively). Mean infarct volume of the 15 mg/kg-treated group was only 4% that
      of the untreated group. There were no postoperative deaths in any treated group
      compared with a death rate of 36% in the untreated group. Mean values for
      vascular smooth muscle contractility to histamine and relaxation to acetylcholine
      were significantly enhanced in vessels from treated rabbits. These studies
      indicate that pretreatment with clentiazem offers cerebral protection and
      significantly reduces infarct volume as well as arterial wall damage beyond the
      occlusion.

PMID- 2003290
TI  - Detection of arterial emboli using Doppler ultrasound in rabbits.
AB  - The purpose of this study was to develop an animal model that could be used to
      test the ability of Doppler ultrasound to detect arterial emboli composed of
      materials that are often involved in cerebral emboli. Emboli introduced into the
      rabbit aorta via the left renal artery consisted of clotted whole blood,
      platelets, atheromatous material, fat, or air. The ultrasound examination was
      carried out continuously during the studies using a multifrequency transcranial
      Doppler apparatus with a 2-MHz probe, a sample volume of 15 mm, at a depth of 15
      mm. The intensity of the Doppler spectrum was measured and displayed as a 15
      shade color scale, each shade representing a 3-dB difference. The diameter of the
      aorta at the site of the ultrasound examination was similar to the diameter of
      the middle cerebral artery in humans. All 125 emboli introduced were clearly
      detected because they caused a Doppler signal at least 15 dB greater than that of
      the surrounding blood. These results show that the potential for emboli detection
      using Doppler ultrasound in the clinical situation is now considerable.

PMID- 2003291
TI  - Quantitative proton magnetic resonance imaging in focal cerebral ischemia in rat
      brain.
AB  - Proton magnetic resonance (MR) imaging has been recommended as a diagnostic tool
      for the detection of focal cerebral ischemia. We compared microscopic MR images
      of rat brains after focal cerebral ischemia with evidence of histological damage
      found on corresponding silver-impregnated or cresyl violet-stained brain
      sections. Ten male Wistar rats were subjected to permanent unilateral occlusions
      of the right middle cerebral and common carotid arteries under halothane
      anesthesia. Twenty-four hours later the area of injury on MR images amounted to
      26% of the total slice area, whereas only 9% of the total slice area was necrotic
      on histological sections from the same animals. The infarcted areas on tissue
      sections were surrounded by regions of selective neuronal injury in the cerebral
      cortex and occasionally in the hippocampus. The area of injury on MR images was
      larger than the combined areas of infarction and selective neuronal injury on
      histological sections. Areas of increased T2 values on MR images extended
      medially into noninfarcted striatum and laterally and dorsally into noninfarcted
      cortex. The lateral and dorsal areas on MR images frequently coincided with
      cortical areas in which considerable selective neuronal injury was present in the
      upper cortical layers. We hypothesize that the abnormal areas on MR images above
      histologically normal brain tissue represent the ischemic penumbra. If true, this
      is the first demonstration of the ischemic penumbra by MR imaging and may reflect
      our use of Wistar rats, a new image analysis technique, and ultra-high resolution
      MR imaging.

PMID- 2003292
TI  - Turner's syndrome, fibromuscular dysplasia, and stroke.
AB  - We report a 43-year-old woman who presented with a right frontoparietotemporal
      ischemic stroke. She had been diagnosed with Turner's syndrome during childhood
      and had a history of chronic estrogen therapy. Cerebral angiography showed
      lesions characteristics of fibromuscular dysplasia involving the right internal
      carotid and right vertebral arteries. We are not aware of any previous reports
      describing an association between fibromuscular dysplasia and Turner's syndrome.
      Although chronic estrogen therapy cannot be ruled out as a cause of this
      patient's stroke, we suggest a possible etiologic relation between these two
      entities.

PMID- 2003293
TI  - Babinski-Nageotte syndrome on magnetic resonance imaging.
AB  - A 70-year-old woman developed left hypoglossal nerve palsy, a right hemiparesis
      sparing the face, and a typical left Wallenberg's syndrome. These symptoms
      resulted from a lesion in the left half of the medulla oblongata, suggesting
      Babinski-Nageotte syndrome, a rare cerebrovascular disease. This is the first
      case of ischemic infarction in the territory of the left vertebral artery and
      posterior inferior cerebellar artery demonstrated on magnetic resonance imaging.
      Severe bilateral lesions of the distal vertebral arteries demonstrated on digital
      subtraction angiography may have contributed to the development of this syndrome.

PMID- 2003294
TI  - Genetic aspects of cerebrovascular disease.

PMID- 2003295
TI  - Intracerebral hematomas during anticoagulant treatment.

PMID- 2003296
TI  - Cerebral venous thrombosis in systemic lupus erythematosus.

PMID- 2003297
TI  - Relationship between platelet and white blood cell counts during the early phase
      of cerebral infarction.

PMID- 2003298
TI  - The significance of carotid bruits.

PMID- 2003299
TI  - Racial differences in cerebrovascular disease hospitalizations.
AB  - We studied the relationship of race to incidence of hospitalization for
      cerebrovascular disease among 74,096 white and 33,041 black persons who took
      health examinations in a prepaid health care program. Analyses were controlled
      for age, sex, body mass index, coffee use, smoking, alcohol use, systolic blood
      pressure, and baseline disease. Blacks were at higher hospitalization risk than
      whites for hemorrhagic cerebrovascular disease (relative risk = 2.4, 95%
      confidence interval = 1.3-5.8), cerebral thrombosis (relative risk = 1.9, 95%
      confidence interval = 1.2-2.9), and nonspecific cerebrovascular disease (relative
      risk = 1.6, 95% confidence interval = 1.2-2.2) but at lower hospitalization risk
      for extracranial occlusive disease (relative risk = 0.4, 95% confidence interval
      = 0.2-0.7). Blood pressure had a similar relation to all types of cerebrovascular
      disease in both races, but there were disparities in the relations of other
      atherosclerosis risk factors to different types of cerebrovascular disease.
      Educational attainment had little relation to hospitalization for extracranial
      occlusive disease, a finding that reduces the likelihood that selection bias
      explains the racial disparity. These data show unexplained racial differences in
      the type and location of cerebrovascular disease. The differences are important
      in understanding the pathogenesis of cerebrovascular disease and have practical
      clinical implications.

PMID- 2003300
TI  - One-year outcome after cerebral infarction in whites, blacks, and Hispanics.
AB  - Little is known about outcome after cerebral infarction for different ethnic
      groups. Of 590 stroke patients hospitalized from 1983 to 1986 at the Neurological
      Institute, cerebral infarction over age 39 years occurred in 135 whites, 177
      blacks, and 82 Hispanics. Outcome after cerebral infarction differed by
      ethnicity. The 1-month mortality rate was similar in whites and blacks and least
      in Hispanics. Whites had a slightly greater risk of recurrent stroke or death
      than blacks or Hispanics until 6 months after infarction, when their risk
      stabilized, while the risk in blacks and Hispanics continued to rise for the
      entire year of follow-up. By 1 year, the rate of recurrent stroke or death was
      34.8 +/- 4.2% in whites, 31.1 +/- 3.6% in blacks, and 21.4 +/- 4.8% in Hispanics
      (p = 0.04). Differences were found in the distribution of various stroke risk
      factors in the three ethnic groups. A Cox proportional hazards model demonstrated
      that the ethnic differences in stroke risk factors and infarct subtype were
      responsible for the ethnic differences in outcome. An abnormal first
      electrocardiogram was a risk factor for stroke recurrence or death in all three
      ethnic groups, while a nonlacunar infarct subtype and a history of diabetes were
      significant only in Hispanics. Understanding the associations of stroke
      determinants with ethnicity may lead to more focused secondary prevention of
      recurrent stroke.

PMID- 2003301
TI  - Probability of stroke: a risk profile from the Framingham Study.
AB  - A health risk appraisal function has been developed for the prediction of stroke
      using the Framingham Study cohort. The stroke risk factors included in the
      profile are age, systolic blood pressure, the use of antihypertensive therapy,
      diabetes mellitus, cigarette smoking, prior cardiovascular disease (coronary
      heart disease, cardiac failure, or intermittent claudication), atrial
      fibrillation, and left ventricular hypertrophy by electrocardiogram. Based on 472
      stroke events occurring during 10 years' follow-up from biennial examinations 9
      and 14, stroke probabilities were computed using the Cox proportional hazards
      model for each sex based on a point system. On the basis of the risk factors in
      the profile, which can be readily determined on routine physical examination in a
      physician's office, stroke risk can be estimated. An individual's risk can be
      related to the average risk of stroke for persons of the same age and sex. The
      information that one's risk of stroke is several times higher than average may
      provide the impetus for risk factor modification. It may also help to identify
      persons at substantially increased stroke risk resulting from borderline levels
      of multiple risk factors such as those with mild or borderline hypertension and
      facilitate multifactorial risk factor modification.

PMID- 2003302
TI  - Correlation of common carotid flow volume measured by ultrasonic quantitative
      flowmeter with pathological findings.
AB  - To evaluate the possibility of quantitatively diagnosing carotid and cerebral
      atherosclerosis noninvasively, we measured common carotid flow volume in 60 sides
      (30 patients), using an ultrasonic quantitative flowmeter, and then compared
      these findings to the severity score of carotid and cerebral atherosclerosis as
      determined at autopsy. Stenosis decreased common carotid flow volume in the
      carotid and cerebral arteries. Increases in the severity score varied inversely
      with reduced flow volume, which was high in inverse correlation (r = -0.696).
      Patients with flow volumes of 8.5 ml/sec or greater did not have stenosis greater
      than or equal to 75%, whereas all patients with flow volumes of 6.4 ml/sec or
      less had stenosis greater than or equal to 50%, with 45% of these having stenosis
      greater than or equal to 75%. These pathological findings confirm that the common
      carotid flow volume reflects the degree of carotid and cerebral atherosclerosis
      present and that the lower limit of common carotid flow volume in healthy
      subjects is 6.5 ml/sec.

PMID- 2003303
TI  - Effects of dextromethorphan on rat brain during ischemia and reperfusion assessed
      by magnetic resonance spectroscopy.
AB  - Using proton and phosphorus magnetic resonance spectroscopy, we evaluated the
      metabolic effects of preischemic administration of the N-methyl-D-aspartate
      antagonist dextromethorphan (50 mg/kg i.p.) during global forebrain ischemia and
      subsequent reperfusion in rats. Dextromethorphan-treated animals (n = 10) showed
      less lactate formation during ischemia than untreated animals (n = 11, p less
      than 0.001). During reperfusion, the lactate level in the treated group was
      reduced (p less than 0.05). Tissue pH declined less in the treated group during
      ischemia (p less than 0.01). There was no difference in the
      phosphocreatine/inorganic phosphate peak height ratio between groups. During
      ischemia, the N-acetylaspartate resonance peaks decreased in both groups.
      Histologic damage assessed in the hippocampal CA1 region 7 days after the
      ischemic insult was more severe in the untreated group (p less than 0.05). There
      was a significant correlation between end-ischemic tissue pH and hippocampal
      damage (r = -0.73, p less than 0.05). In the dextromethorphan-treated animals,
      90% of the rats survived compared with 47% of the untreated animals (p less than
      0.05). These results support findings in previous studies that dextromethorphan
      attenuates ischemic damage.

PMID- 2003304
TI  - Air embolism of the brain in rabbits pretreated with mechlorethamine.
AB  - Infusion of 400 microliters air into the left internal carotid artery of five
      anesthetized rabbits caused transient pial arteriole air embolism, an immediate
      41.9 +/- 0.8% dilatation of the embolized vessels, suppression of the cortical
      somatosensory evoked response to 29.4 +/- 2.7% of baseline, and a progressive
      decline in ipsilateral cerebral blood flow (measured by hydrogen clearance) to 46
      +/- 4.1% of baseline after 2 hours. These values were significantly different
      from those at baseline and from the responses of 10 control rabbits given
      equivalent intracarotid saline infusions. Twelve other rabbits were made
      leukopenic by treatment with 1.5 mg/kg i.v. mechlorethamine 72 hours prior to
      study. Mean +/- SEM leukocyte count decreased from 6,320 +/- 73/mm3 to 1,890 +/-
      66/mm3 without any change in the leukocyte differential or erythrocyte and
      platelet counts. Intracarotid infusion of saline into seven of the leukopenic
      rabbits caused no changes. In the other five leukopenic rabbits, infusion of 400
      microliters air caused air embolism but did not produce the anticipated declines
      in cerebral blood flow or the cortical somatosensory evoked response, both of
      which remained indistinguishable from baseline values and responses in the seven
      saline-treated leukopenic controls. Similarly, air-embolized arterioles showed
      nonsignificant dilatation in leukopenic rabbits. Our data suggest that the
      decreases in both cerebral blood flow and brain function seen after air embolism
      require the presence of leukocytes.

PMID- 2003305
TI  - Postischemic (S)-emopamil therapy ameliorates focal ischemic brain injury in
      rats.
AB  - (S)-Emopamil is a calcium channel blocker of the phenylalkylamine class, having
      potent serotonin S2 antagonistic properties and high blood-brain barrier
      penetrability. Previous studies have documented cerebroprotective effect in
      animal models of both focal and global ischemia. The present study was undertaken
      to define the postischemic "window" of therapeutic efficacy for this agent.
      Sprague-Dawley rats were subjected to permanent proximal middle cerebral artery
      occlusion, combined with an initial 30-minute period of halothane-induced
      hypotension (50 mm Hg). (S)-Emopamil (20 mg/kg) was administered
      intraperitoneally either 20-30 minutes prior to middle cerebral artery occlusion
      or 1 hour, 2 hours, or 3 hours following occlusion. Treated groups received a
      second similar dose 2.5 hours later and twice daily for 2 days thereafter. Brains
      were perfusion-fixed on the third day. Planimetric analysis of hemotoxylin and
      eosin-stained coronal brain sections documented a cortical infarct averaging 72.9
      +/- 33.3 mm3 (mean +/- SD) in untreated rats. Cortical infarct volume was reduced
      by 48% (to 37.6 +/- 27.6 mm3) when therapy was initiated 1 hour postischemia (p
      less than 0.05). When treatment was deferred to 2 hours postichemia, mean
      cortical infarct volume was reduced by 34%, but this difference did not attain
      statistical significance. Infarct volume in rats with treatment initiated at 3
      hours postischemia was indistinguishable from that in controls. Striatal infarct
      volume was similar in all groups. These results document a postischemic
      therapeutic window of cerebroprotection for (S)-emopamil lying between 1 and 2
      hours after middle cerebral artery occlusion.

PMID- 2003306
TI  - Effects of tirilazad mesylate on postischemic brain lipid peroxidation and
      recovery of extracellular calcium in gerbils.
AB  - We describe the effects of the 21-aminosteroid tirilazad mesylate (U-74006F) on
      postischemic lipid peroxidation (depletion of brain vitamin E) and cortical
      extracellular calcium recovery in gerbils subjected to 3 hours of unilateral
      carotid artery occlusion. Male gerbils were treated with either 0.2 ml vehicle
      (0.05N HCl) or 10 mg/kg i.p. U-74006F 10 minutes before the induction of ischemia
      and again immediately after the initiation of reperfusion. In the first series of
      experiments, the brain concentration of vitamin E, which was unaffected by
      ischemia without reperfusion, was decreased after 2 hours of reperfusion by an
      average of 60% in vehicle-treated animals compared with sham-operated animals; in
      the U-74006F-treated gerbils, the 2-hour postischemic vitamin E loss was only 27%
      (p less than 0.002 different from vehicle-treated animals). In the second series,
      unilateral carotid artery occlusion produced a decrease in the cortical
      extracellular calcium concentration from 1.05 mM before ischemia to 0.11 mM by
      the end of the ischemic episode in both vehicle- and U-74006F-treated gerbils.
      After 2 hours of reperfusion, the calcium concentration had recovered to only
      0.22 mM in the vehicle-treated animals compared with 0.56 mM in the U-74006F
      treated group (p less than 0.01). Cortical blood flow, mean arterial blood
      pressure, and blood gases did not differ significantly between the two treatment
      groups. Administration of only the immediate postreperfusion dose (i.e., no
      pretreatment) also significantly improved the recovery of cortical extracellular
      calcium. The results indicate that U-74006F inhibits postischemic lipid
      peroxidation as assessed by the preservation of brain vitamin E and that,
      secondary to this membrane-protective effect, the processes responsible for the
      reversal of ischemia-triggered intracellular calcium accumulation are preserved.

PMID- 2003307
TI  - Adventitial red blood cells produce intimal platelet accumulation in cerebral
      arteries of cats following subarachnoid hemorrhage.
AB  - After dividing 21 cats into three equal groups, we exposed their right middle
      cerebral arteries transorbitally and adventitially irrigated them with 2 ml
      washed red blood cells, blood plasma, or saline. To determine arterial intimal
      platelet accumulation in each cat, we injected [111In]oxine-labeled platelets
      intravenously immediately before injecting the various experimental solutions.
      Animals were sacrificed 2 or 4 hours following the injection of labeled
      platelets. Irrigation with washed red blood cells produced a significantly
      greater intraluminal accumulation of platelets than irrigation with saline (p
      less than 0.05). Plasma tended to have less of an effect on platelet accumulation
      than washed red blood cells, but this difference was not significant. These data
      suggest that the adventitial blood fraction responsible for intimal platelet
      accumulation in cerebral arteries following subarachnoid hemorrhage may be
      derived mainly from the red blood cell fraction.

PMID- 2003308
TI  - Development of a new perfusion system for pharmacological study on rabbit basilar
      arteries.
AB  - We developed a constant-flow perfusion system to measure vascular responses to
      vasoactive agents applied intraluminally or extraluminally. The intraluminal and
      extraluminal sides of a cylindrical section of rabbit basilar artery were
      isolated completely. By loading with 0.75 g of tension, the resting condition of
      each preparation was made constant. The intraluminal side was perfused at a
      constant flow of 8 ml/min and under an intraluminal pressure of 8 mm Hg. When 30
      mM KCl was administered intraluminally the preparation showed marked contraction,
      whereas only slight contraction was observed with extraluminal administration.
      When 2 x 10(-7) M 5-hydroxytryptamine was administered, no significant
      differences in contraction could be detected between the intraluminal and
      extraluminal routes. Application of 10(-6) to 10(-4) M acetylcholine after
      precontraction with 30 mM KCl resulted in much stronger dilatation upon
      intraluminal application. Thus, it was demonstrated that under certain conditions
      significant differences exist in the responses of rabbit basilar arteries to
      vasoactive agents applied intraluminally or extraluminally. This system can
      detect the effects of vasoactive agents administered intraluminally and
      extraluminally at a high level of sensitivity and shows good reproducibility as a
      means of analyzing vascular functions and characteristics.

PMID- 2003309
TI  - Beagle pup germinal matrix maturation studies.
AB  - Intraventricular hemorrhage, or hemorrhage into the germinal matrix tissues of
      the developing brain, remains a common problem of preterm infants. The "risk
      period" for this insult is the first 3-4 postnatal days. We hypothesized that
      this risk period for hemorrhage is related to rapid perinatal maturation of the
      germinal matrix vasculature and employed the newborn beagle pup model for the
      study of this maturation. Newborn beagle pups (n = 30) were anesthetized and
      systemically perfused with buffered formalin; the brains were removed and
      prepared for immunohistochemical study. Sections stained with Bandeiraea lectin
      demonstrated that there was no difference in germinal matrix vessel density
      between postnatal days 1 and 4. Germinal matrix sections were also stained for
      antibodies to alpha-smooth muscle actin, collagen IV, collagen V, desmin, factor
      VIII-related antigen, fibronectin, glial fibrillary acidic protein, laminin,
      transferrin, and vimentin. Vasculature staining by alpha-smooth muscle actin was
      not noted until postnatal day 10, and differential staining was detected for
      antibodies to laminin and collagen V. Quantification of staining intensity by
      confocal microscopy demonstrated a significant increase in both extracellular
      matrix components at postnatal day 4 compared with day 1 (p less than 0.05 for
      both). These basement membrane proteins may add sufficient structural integrity
      to germinal matrix vessels to prevent capillary rupture and thus intraventricular
      hemorrhage.

PMID- 2003310
TI  - Thrombosis in a congenitally bifurcated superior sagittal sinus.
AB  - A 26-year-old woman had a peripartum venous thrombotic stroke involving the right
      parietal lobe. The initial thrombus was present only in the right channel of a
      congenitally bifurcated superior sagittal sinus. This diagnosis and subsequent
      thrombus extension were readily shown by magnetic resonance imaging in contrast
      to equivocal angiography. A subsequent, prospective review of 100 patients
      undergoing cranial magnetic resonance imaging showed the presence of similarly
      bifurcated superior sagittal sinuses in two. The patient stabilized after therapy
      with intravenous heparin, but switching her medication to oral warfarin sodium
      was followed by clinical deterioration and propagation of the thrombus,
      necessitating resumption of intravenous heparin. No coagulopathy was identified.

PMID- 2003311
TI  - Cerebral venous thrombosis with plasminogen deficiency.
AB  - We describe a patient with inherited plasminogen deficiency who developed
      extensive cerebral venous thrombosis. Several other conditions that might have
      contributed to a hypercoagulable state, including mild thrombocytosis,
      thyrotoxicosis, and a chronic inflammatory lung disorder, were present. We also
      discuss the evidence linking plasminogen deficiency with a thrombophilic state.
      The diagnosis of cerebral venous thrombosis in this case was readily established
      by nuclear magnetic resonance imaging, a technique that is ideally suited for the
      evaluation and follow-up of patients with this condition.

PMID- 2003312
TI  - Stroke after heavy marijuana smoking.
AB  - I examined two young men who developed cerebral infarction associated with heavy
      marijuana smoking. Both were light tobacco smokers, but they did not drink
      alcohol or use other street drugs. Diagnostic work-up for nonatherosclerotic
      causes of stroke was unremarkable. I postulate that marijuana-associated
      alterations in systemic blood pressure resulted in vasospasm, leading to strokes
      in these patients.

PMID- 2003313
TI  - Scleroderma and central nervous system vasculitis.
AB  - We describe a patient with scleroderma (CREST syndrome) and central nervous
      system vasculitis. While angiography demonstrated segmental symmetrical arterial
      narrowing characteristic of vasculitis, results of leptomeningeal biopsy were
      normal. There was no evidence of systemic vasculitis, renal failure, or malignant
      hypertension previously thought to be required to explain central nervous system
      dysfunction in patients with scleroderma. Signs and symptoms attributable to
      vasculitis were reversible with aggressive immunosuppressive therapy.

PMID- 2003314
TI  - Noninfectious thrombosis of the superior sagittal sinus in a patient with iron
      deficiency anemia.

PMID- 2003315
TI  - Vascular headaches and the anticardiolipin antibodies.

PMID- 2003316
TI  - Bilateral loss of vision in bright light.

PMID- 2003317
TI  - Dementia after stroke.

PMID- 2003319
TI  - Transfusion-induced immunomodulation and infection.

PMID- 2003318
TI  - Are there better ways than the crossmatch to demonstrate ABO incompatibility?

PMID- 2003320
TI  - Effect of delayed centrifugation or reading on the detection of ABO
      incompatibility by the immediate-spin crossmatch.
AB  - The immediate-spin (IS) crossmatch is a method that detects ABO incompatibility.
      However, under certain circumstances, this test may show unwanted negative or
      weak results, even though the red cells (RBCs) and serum being tested are ABO
      incompatible with each other. The present study investigated the potential effect
      of delayed centrifugation or reading on the IS crossmatch test performance. When
      the centrifugation step of the IS crossmatch between group O sera and group A1
      RBCs was delayed for 2 minutes, 5 of 200 crossmatches showed no agglutination
      with only trace (n = 2) or moderate (n = 3) hemolysis, and one crossmatch showed
      only weak, macroscopic agglutination, but moderate hemolysis. All six sera
      contained A antibodies that were lytic in vitro and, therefore, probably were
      capable of causing in vivo hemolysis of transfused A1 RBCs. Delaying the reading
      of the IS crossmatch test for 2 minutes had no apparent effect on test
      performance. These data demonstrate the importance of technologists' recognition
      of hemolysis as a positive result on IS crossmatches, especially if the
      performance of the centrifugation step of the test is delayed. Furthermore, the
      unwanted negative agglutination results were abolished by suspending the group A1
      RBCs in saline containing EDTA. The authors' laboratory has modified its IS
      crossmatch procedure so that donor RBCs are routinely suspended in saline
      containing EDTA before testing. This procedural change should increase the safety
      of the IS crossmatch.

PMID- 2003321
TI  - No evidence of frequent human immunodeficiency virus type 1 infection in
      seronegative at-risk individuals.
AB  - The possible existence of human immunodeficiency virus type 1 (HIV-1) infection
      in asymptomatic seronegative at-risk individuals was investigated in a
      prospective study of 55 seronegative high-risk individuals (42 homosexual men and
      13 heterosexual individuals) and 32 seronegative hemophiliacs treated with factor
      VIII or IX concentrates before viral inactivation by heat treatment and
      systematic screening of blood donations. Tests used include the polymerase chain
      reaction assay with three primer pairs (one in the gag region and two in the pol
      region) and tests for serum p24 antigen, anti-nef serology (Western blot), and
      five biologic markers frequently altered by HIV infection (CD4 lymphocyte count,
      serum beta 2-microglobulin and neopterin concentration, and serum IgG and IgA
      concentration). Although 91 of 92 HIV-1-seropositive persons were positive in
      testing with at least one primer pair, no positive result was observed in
      seronegative at-risk individuals or in 117 seronegative low-risk controls. No nef
      antibody was found in seronegative at-risk individuals or seronegative controls,
      but 44 (47%) of 92 HIV-1-seropositive persons had nef antibodies. These findings
      do not support the existence of frequent HIV-1 infection in seronegative at-risk
      individuals.

PMID- 2003322
TI  - Infection or suspected infection after hip replacement surgery with autologous or
      homologous blood transfusions.
AB  - Homologous blood transfusions have been associated in both animals and humans
      with an increased risk of acute postoperative infectious complications. Eighty
      four patients who underwent hip replacement surgery and were transfused with 2 or
      3 units of blood were analyzed to determine whether those receiving homologous
      transfusions had different outcomes than those receiving autologous blood only.
      Only patients free of other risks for postoperative infection were studied. Those
      receiving homologous blood had a 32 percent (16/50) rate of proven or suspected
      infections, which was significantly higher than the 3 percent (1/34) rate in
      patients receiving autologous blood (p = 0.0029). Wound infections accounted for
      only a minority (6/17) of the proven or suspected infections, which suggests that
      nonsurgical factors contributed to these complications. The patients identified
      as being infected required significantly more antibiotic therapy (mean, 7.6 days)
      and lengthier hospital stays (mean, 15.5 days) than the patients who remained
      free of evidence of infection (means: 2.3 days of antibiotics and 12.3 days in
      the hospital) (p = 0.0001 for each variable). Other potential risk factors for
      infection, such as duration of surgical procedure, advanced patient age, amount
      of blood loss, type of anesthesia, surgeon performing the operation, use of a
      cemented versus porous-coat prosthesis, leukocytopenia, anemia, and underlying
      medical diagnosis, did not account for the differences in infection rates seen in
      those receiving homologous and autologous transfusions. These results confirm
      previous reports of an increased risk of postoperative infection in patients
      receiving homologous transfusions. Homologous transfusion may contribute to an
      increased risk of infection by immunologic modulation of the recipient.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 2003323
TI  - Inhibition of in vitro adherence of antibody-coated red cells to monocytes by the
      dialyzable leukocyte extract.
AB  - The red cell-monocyte assay (RMA), which has been used to evaluate the clinical
      significance of red cell (RBC) antibodies, was employed to test the effect of the
      dialyzable leukocyte extract (DLE) on in vitro adherence to monocytes of human
      RBCs coated with alloantibodies or autoantibodies. The total association index
      (TAI) of the RMA, expressing the number of RBCs adhering to or phagocytosed by
      100 monocytes, indicated a potent inhibitory activity of DLE in the test system.
      TAI values of 100.4 +/- 20.1 (mean +/- SD) in the control sample, consisting of
      RBCs coated in vitro with anti-D, dropped to 4.0 +/- 2.1 when DLE was present in
      the assay medium at a concentration of 0.5 U per mL. Similar results were
      obtained with RBCs coated with IgG antibodies in vivo. The inhibition was dose
      dependent and was associated with a thermolabile component of DLE. This study
      establishes that DLE can modulate monocyte function by inhibiting the recognition
      of IgG sensitized red cells.

PMID- 2003324
TI  - Heterogeneity of human red cell autoantibodies assessed by isoelectric focusing.
AB  - Human red cell (RBC) autoantibodies may be the products of a single lymphocyte
      clone or of a restricted number of clones. For insight into the clonal
      distribution of human RBC autoantibodies, serum fractions from 28 individuals
      with various forms of autoimmune hemolytic anemia (AHA) and two nonanemic
      individuals with positive direct antiglobulin tests were separated by isoelectric
      focusing (IEF), and RBC binding in each fraction was quantitated with a solid
      phase radioimmunoassay. IEF fractions of serum from normal volunteers and
      patients with nonimmune hemolytic anemia served as controls. These studies
      indicate that RBC antibodies are found in a restricted number of IEF fractions in
      sera from some patients with immune hemolytic anemia. IEF fractions containing
      RBC-binding activity vary among patients with idiopathic AHA, and distinct
      patterns of binding activity are found in serum from some patients with AHA
      associated with alphamethyldopa and procainamide or with B-cell
      immunoproliferative diseases. These findings suggest that the mechanism leading
      to autoantibody production may differ among patients with the various forms of
      immune hemolytic anemia.

PMID- 2003325
TI  - Donor room personnel attitudes toward autologous donors.
AB  - Patients with serious illnesses who donate their blood for autologous use create
      anxiety for many phlebotomists. Donor room staff were surveyed at three donor
      centers, using confidential questionnaires, to identify their concerns and to
      evaluate factors associated with reduced anxiety toward autologous donors. Among
      respondents (n = 93), 58 percent had patient care experience within the last 5
      years, which correlated with diminished concern about phlebotomizing cardiac
      patients (r = .21; p = 0.04). Fifty-seven percent of respondents had drawn blood
      from greater than 50 autologous donors. Surprisingly, the experience of drawing
      blood from relatively large numbers of autologous donors did not correlate with
      increased confidence in phlebotomizing pediatric, cardiac, and elderly patients
      (r = -.04; p = 0.75). Those respondents who felt that they had adequate medical
      support agreed with more liberal donor criteria and were more confident about
      phlebotomizing pediatric, cardiac, and elderly patients (r = -.32; p = 0.001).
      Those respondents who believed most strongly in the benefits of autologous
      transfusion had the least anxiety toward donors who were medically more complex
      (r = .39; p = 0.0001). It is concluded that, contrary to what might be expected,
      phlebotomizing large numbers of autologous donors does not reduce the anxiety of
      staff members when they encounter donors with complex medical problems. Factors
      that do reduce anxiety include dependable physician and other medical support
      services, previous experience in direct patient care, and knowledge of the
      benefits of autologous transfusion.

PMID- 2003326
TI  - Assessment of clinical significance of anti-Ge in an untransfused man.
AB  - A 19-year-old, untransfused Melanesian man from Papua New Guinea was admitted to
      the hospital for repair of an atrial septal defect. His serum contained an
      alloantibody that reacted strongly on the indirect antiglobulin test and was
      identified as anti-Ge. Gerbich-negative blood was transfused following urgent
      surgery. A 51Cr red cell survival study performed 2 weeks after surgery yielded
      zero survival of Gerbich-positive cells after 24 hours. A monocyte-driven,
      antibody-dependent, cell-mediated cytotoxicity assay performed on both
      pretransfusion and posttransfusion serum samples and on concentrated serum showed
      less than 1 percent specific lysis of Gerbich-positive cells. This did not
      correlate with the indication of clinical significance predicted by the 51Cr
      study. Red cell adherence and phagocytosis, not evident in a monocyte monolayer
      assay using native serum, were demonstrable in 16 percent of monocytes by the use
      of concentrated serum.

PMID- 2003327
TI  - The critical role of blood from HLA-homozygous donors in fatal transfusion
      associated graft-versus-host disease in immunocompetent patients.
AB  - Fatal transfusion-associated graft-versus-host disease developed in a 69-year-old
      woman with colon cancer who underwent elective hemicolectomy. During the
      perioperative period, she was transfused with 4 units of nonirradiated fresh
      whole blood less than 6 hours after the blood was donated by family members. She
      was immunocompetent and was not treated with any immunosuppressive agents such as
      corticosteroids, chemotherapy, or irradiation therapy. The implicated donor was
      thought to be her daughter, who was homozygous for an HLA haplotype that was
      shared with the recipient: A24, Bw52, CBL, DR2. This is the most common haplotype
      in the Japanese population. This case and others in the Japanese literature
      indicate that the transfusion of fresh, nonirradiated blood that contains
      immunocompetent lymphocytes and peripheral hematopoietic precursor cells from HLA
      homozygous donors can be lethal to the recipient.

PMID- 2003328
TI  - Immunoadsorption for coagulation factor inhibitors.
AB  - Inhibitors to coagulation factors are among the most difficult problems in the
      management of coagulation disorders. Most presently available therapy does not
      assure hemostasis. An extracorporeal immunoadsorption system, which selectively
      binds IgG, was used to lower inhibitor levels in eight patients on 10 occasions.
      In this system, separated plasma is delivered to two staphylococcal protein A
      Sepharose columns, which are coupled to an elution monitor. Columns are eluted
      sequentially and regenerated to maximize IgG removal. Successful removal of the
      inhibitor was accomplished in all six hemophiliacs on seven occasions, as well as
      in a patient with acquired von Willebrand disease. All patients whose inhibitors
      were lowered to less than 10 Bethesda units achieved measurable factor levels
      when factor concentrate replacement was given. Immunoadsorption facilitates
      efficient removal of inhibitors, which allows factor replacement therapy.

PMID- 2003329
TI  - Tissue transplant-transmitted infections.
AB  - Tissue bankers, as well as those transplanting tissues, have been sensitized to
      the possibility of transmission of fatal infection via tissue transplants,
      particularly following recent reports of a few cases of AIDS or HIV infection
      from bone, semen, and skin grafts. It is beyond the scope of this review to
      describe the steps taken by tissue banks to enhance the safety of tissue
      transplants. Of note is the fact that a number of new donor screening tests, such
      as those for antibody to HIV, HBcAg, hepatitis C virus, and human T cell
      lymphotropic virus type I, have recently been implemented. In addition, rapid
      advances in the medical history screening of tissue donors and tissue
      procurement, processing, and preservation continue. Viral inactivation studies
      are also being undertaken. All these measures are being introduced to increase
      the safety of tissue transplants.

PMID- 2003330
TI  - Risks of donation reactions among autologous and homologous donors.

PMID- 2003331
TI  - Adsorption of anti-Cra by human platelet concentrates.

PMID- 2003332
TI  - Confidential unit exclusion (CUE) is just another test.

PMID- 2003333
TI  - Coordination of gene expression in the formation of mammalian mitochondria.

PMID- 2003334
TI  - Chemical mutagenesis and fine-structure functional analysis of the mouse genome.
AB  - Heritable mutations constitute important raw materials for mammalian
      developmental genetics and general genome studies. Mutations induced by high
      efficiency chemical mutagenesis of germ cells in mice can be used in genetic and
      molecular studies to complement physical-mapping strategies and to examine the
      nature and extent of the functional complexities hidden within the mammalian
      genome.

PMID- 2003335
TI  - PCR on dried skin and liver extracts from the same individual gives identical
      products.

PMID- 2003336
TI  - Rapid detection of single base mismatches as heteroduplexes on Hydrolink gels.

PMID- 2003337
TI  - Regulation of HIV gene expression by RNA-protein interactions.
AB  - Human immunodeficiency virus (HIV) gene expression is tightly controlled through
      the interaction of trans-acting regulatory proteins with the many cis-acting
      elements present in viral DNA and RNA. Two proteins encoded by HIV, referred to
      as Tat and Rev, are essential positive regulators of gene expression. Recent work
      shows that these proteins control HIV gene expression through interaction with
      RNA target elements present within the 5' untranslated leader sequence and
      envelope gene, respectively. There is evidence that these interactions in
      themselves are not sufficient to confer regulation without the presence of
      additional host cell factors.

PMID- 2003338
TI  - Antimicrobials in the '90s: expanded options for effective patient care.
      Proceedings of a symposium on ofloxacin. May 4-5, 1990.

PMID- 2003339
TI  - Evaluating results of clinical trials in treatment of complicated urinary tract
      infection.
AB  - Clinical trials of new drugs should produce results that are not due to chance,
      inherent differences in groups, or handling of the groups by the investigator.
      These sources of error may be prevented by having groups of a size that provides
      sufficient statistical power and thus rules out sample variation. Differences in
      groups can be prevented by randomization, and double blinding the subjects
      prevents investigator bias.

PMID- 2003340
TI  - Parenteral ofloxacin in treatment of pyelonephritis.
AB  - The interim findings of two studies of intravenous ofloxacin for the treatment of
      pyelonephritis are presented. The findings are from one center of a multicenter
      trial. In the first study intravenous (IV) ofloxacin was given to 34 patients
      with urine-culture-positive pyelonephritis. After three days of intravenous
      therapy patients could be switched to oral ofloxacin. Microbiologic eradication
      occurred in 97 percent and clinical cures in 97 percent of the patients treated
      with ofloxacin. There were three probable drug-related adverse events. In the
      second comparative study 38 patients with pyelonephritis were randomized to
      receive IV ofloxacin with the option of switching to oral ofloxacin after three
      days. IV ceftazidime was given to 30 patients with pyelonephritis with the option
      of switching to trimethoprim/sulfamethoxazole (TMP/SMX) after three days.
      Microbiologic cures were experienced by 97 percent of the ofloxacin patients and
      by 100 percent of the ceftazidime patients. Probable drug-related adverse
      reactions were experienced by 3/28 ofloxacin patients and by none of the
      ceftazidime patients. These interim study findings indicate that the intravenous
      preparation of ofloxacin is efficacious in the treatment of pyelonephritis and
      that it is safe. In addition, IV ofloxacin is as efficacious as IV ceftazidime
      for the treatment of pyelonephritis.

PMID- 2003341
TI  - Randomized study to evaluate efficacy and safety of ofloxacin vs. trimethoprim
      and sulfamethoxazole in treatment of uncomplicated urinary tract infection.
AB  - The efficacy and safety of ofloxacin taken orally once a day for three days was
      compared with a combination of trimethoprim and sulfamethoxazole (TMP/SMX) taken
      orally twice a day for seven days in the treatment of uncomplicated urinary tract
      infection. The diagnosis was established by the presence of symptoms including
      dysuria, frequency, suprapubic pain, and urgency. Bacteriuria was confirmed by a
      urine culture of a minimum of 10(5) organisms per mL, of at least one species. A
      treatment course of ofloxacin, once-a-day for three days, was as safe and
      effective as a standard course of TMP/SMX, twice a day for seven days.

PMID- 2003342
TI  - Worldwide clinical experience with ofloxacin in urologic cases.
AB  - Ofloxacin is a quinolone carboxylic acid with a broad spectrum of activity for
      gram-negative pathogens that are common causes of urologic infections including
      cystitis, pyelonephritis, and prostatitis. The data in this publication will
      review clinical trials in urologic infections as well as the literature which
      dates from January 1983 through February 1989. The database includes over four
      hundred reports from nineteen foreign countries and involves data from more than
      21,000 patients. The data from the United States were accumulated in clinical
      trials conducted between 1984 and 1988. Ofloxacin has certain attributes that
      make it a potentially useful drug in the treatment of urologic infections. These
      include the high bioavailability from oral administration and the fact that the
      product is excreted almost entirely by the kidney, primarily as the active parent
      compound. Urinary levels of ofloxacin two to four hours postadministration can
      achieve concentrations above 600 micrograms/mL after a single 400-mg dose.
      Urinary levels twenty-four hours after a single dose are noted to be typically
      around 50 micrograms/mL. Both of these concentrations are well above the minimum
      inhibitory concentration (MIC90) for uropathogens, which might be below 1
      microgram/mL for many uropathogens. With respect to the prostate, ofloxacin
      penetrates prostatic tissues well and can achieve concentrations of approximately
      4.5 micrograms per gram of prostate tissue as a mean peak level. Prostate levels
      ten hours postdose will typically be approximately 2.7 micrograms per gram of
      prostatic tissue. These levels exceed the MIC90 for the majority of prostatic
      pathogens as well.

PMID- 2003343
TI  - Bacterial prostatitis: new methods of treatment.
AB  - Four different clinical categories of prostatitis are recognized at present:
      acute bacterial prostatitis, chronic bacterial prostatitis, nonbacterial
      prostatitis, and prostatodynia. Treatment results of chronic bacterial
      prostatitis have, in the past, been rather poor. In addition to local factors
      (e.g., prostatic calculi), the poor results may well be due, in part, to lack of
      penetration of the various drugs used into the prostatic tissue and fluid, mostly
      because of unfavorable lipid solubility, degree of ionization, protein binding,
      and unfavorable pH gradients from the plasma to prostatic fluid. All of these
      factors determine the diffusion of a drug into prostatic tissue and fluid. The
      minimum inhibitory concentrations (MIC) of the various drugs used and the
      concentration of the drugs actually obtained in the prostate, combined with the
      influence of pH, inoculum size, and effect of prostatic fluid and prostatic
      extract on MIC, are important factors in determining at least the theoretical
      efficacy of various drugs in the treatment of chronic bacterial prostatitis. The
      new fluoroquinolones have excellent penetration into both animal and human
      prostates and very low MIC for the infecting organisms and should, from a
      theoretical standpoint, be ideal in the treatment of chronic bacterial
      prostatitis. Few clinical studies have been done, and only prospective,
      randomized clinical trials will determine the relative efficacy of the various
      quinolones in the treatment of chronic bacterial prostatitis.

PMID- 2003344
TI  - Current patterns in nosocomial urinary tract infections.
AB  - Nosocomial infections develop in about 5 percent of patients admitted to acute
      care hospitals in the United States. The genitourinary tract is the primary site
      of infection in about 40 percent of cases, and urinary tract instrumentation and
      catheterization are implicated in about 80 percent of genitourinary tract
      nosocomial infections. Catheter-associated urinary tract infections are a
      frequent source of serious patient morbidity, urosepsis, and even death. The
      pathogenesis, risk factors, consequences, and preventive measures concerning
      nosocomial urinary tract infections are reviewed, and specific guidelines for
      catheter management are offered.

PMID- 2003345
TI  - Liver warning.

PMID- 2003346
TI  - Veterinary involvement in meat inspection.

PMID- 2003347
TI  - Xylazine/ketamine combination in dogs.

PMID- 2003348
TI  - Marine mammal diseases.

PMID- 2003350
TI  - Evaluation of veterinary education in Europe.

PMID- 2003349
TI  - Cervical spondylopathy.

PMID- 2003351
TI  - Challenges ahead for cattle practitioners.

PMID- 2003352
TI  - Lord Soulsby explains zoonoses risks.

PMID- 2003353
TI  - Effect of damage to the teat end on the experimental induction of mastitis in dry
      cows with Corynebacterium pyogenes.
AB  - The teat ends of 12 dry cows were contaminated with Corynebacterium pyogenes. To
      determine whether a pre-existing (an)aerobic bacterial infection of the udder was
      a predisposing factor for a C pyogenes mastitis they included infected and
      uninfected quarters. Anaerobic bacteria could not be found and mastitis was not
      induced. When the teats were contaminated with C pyogenes after the teat ends had
      been injured 30 of the quarters became infected, and anaerobic bacteria were
      demonstrated in many quarters.

PMID- 2003354
TI  - Antagonistic activities of atipamezole, 4-aminopyridine and yohimbine against
      medetomidine/ketamine-induced anaesthesia in cats.
AB  - The objectives of this trial were to determine the ability of atipamezole, 4
      aminopyridine and yohimbine to reverse the anaesthetic effects of a combination
      of medetomidine and ketamine in cats. Forty healthy cats were anaesthetised with
      80 micrograms/kg medetomidine combined with 5 mg/kg ketamine. Thirty minutes
      later atipamezole (200 or 500 micrograms/kg), 4-aminopyridine (500 or 1000
      micrograms/kg) or yohimbine (250 or 500 micrograms/kg) were injected
      intramuscularly. The doses of antagonists were randomised, so that each dose was
      administered to five cats, and 10 cats were injected only with physiological
      saline. Atipamezole clearly reversed the anaesthesia and bradycardia induced by
      medetomidine and ketamine. The mean (+/- sd) arousal times were 28 (+/- 4.7), 5.8
      (+/- 1.8) and 7 (+/- 2.1) minutes in the placebo group, and the groups receiving
      200 and 500 micrograms/kg atipamezole, respectively. The heart rates of the cats
      receiving 200 micrograms/kg atipamezole rapidly returned to values close to the
      initial ones, but 15 minutes after the injection of 500 micrograms/kg atipamezole
      a significant tachycardia was observed. All the cats showed moderate signs of
      ataxia during the recovery period. A dose of 500 micrograms/kg yohimbine also
      clearly reversed the anaesthetic effects of medetomidine/ketamine but 250
      micrograms/kg was not effective. The dose of 500 micrograms/kg allowed a smooth
      recovery with no particular side effects except for some signs of incomplete
      antagonism of the ketamine effects, ie, ataxia and muscular incoordination. With
      4-aminopyridine there were no statistically significant effects on the recovery,
      or the heart and respiratory rates of the cats anaesthetised with
      medetomidine/ketamine.

PMID- 2003355
TI  - Rabies in Sudan: an epidemiological review.

PMID- 2003356
TI  - Caecal anomaly in a domestic fowl.

PMID- 2003357
TI  - Quality assurance in private veterinary laboratories.

PMID- 2003358
TI  - Thyroid adenomata and renal tumours.

PMID- 2003359
TI  - Anti-freeze poisoning.

PMID- 2003360
TI  - Successful pregnancy following non-surgical embryo transfer in llamas.

PMID- 2003361
TI  - The in vitro uptake and metabolism of lignocaine, procainamide and pethidine by
      tissues of the hindquarters of sheep.
AB  - 1. In vitro studies using tissue slices or tissue homogenates of liver, skeletal
      muscle, fat skin and blood were conducted to determine whether the uptake of
      procainamide, lignocaine and pethidine into the hindquarters of sheep was due to
      distribution or metabolism. Both homogenates and slice preparations of liver
      showed significant metabolism or uptake, confirming the viability of the
      preparations. 2. None of the drugs was metabolized in blood and there was minimal
      uptake of the drugs into the skin. 3. There was metabolism of pethidine in
      skeletal muscle and substantial uptake of pethidine into fat, indicating that the
      rapid rate of uptake and prolonged elution of pethidine in the hindquarters was
      due to both distribution and metabolism. 4. No metabolism of lignocaine in muscle
      was found, but there was substantial uptake into fat, indicating that the rapid
      rate of uptake and prolonged elution of lignocaine in the hindquarters was due to
      its distribution into fat. 5. There was negligible uptake of procainamide into
      either muscle or fat, presumably due to its relatively low lipophilicity.

PMID- 2003362
TI  - Kinetics of distribution and elimination of DDE in rats.
AB  - 1. Rats were given single i.v. doses of 14C-DDE, and total drug (14C) and
      unchanged DDE (g.l.c.) were measured for up to 14 days in blood, tissues, and
      excreta. The 14C recoveries amounted to 90.0 +/- 10.8 (SD) % dose. 2. DDE
      underwent redistribution from blood to liver, muscle, skin and, ultimately,
      adipose tissue. The tissue/blood concentration ratios were 6 for liver and
      muscle, 35 for skin, 400 for adipose tissue. Concentrations in blood and lean
      tissues declined biphasically with beta-half-lives of 8-12 days. The half-lives
      for adipose tissue and total body burden were larger by one order of magnitude.
      However, due to the increase of adipose tissue mass with time, the amount of DDE
      stored therein remained constant at almost 60% dose. 3. Except for liver, no
      substantial metabolite concentrations in tissues were found. In particular,
      lipophilic metabolites were clearly absent. Thus, tissue kinetics and storage are
      controlled by unchanged DDE. 4. Of a given dose of DDE, 31% was excreted in the
      faeces as polar metabolites within 14 days, and 3-4% dose as DDE. Urinary
      excretion was negligible. The beta-half-life of faecal excretion was equal to the
      one in blood and lean tissues. It is concluded that excretion is limited by the
      slow formation of polar metabolites of DDE.

PMID- 2003363
TI  - The in vivo blood, fat and muscle concentrations of lignocaine and bupivacaine in
      the hindquarters of sheep.
AB  - 1. A method was developed for sampling muscle and fat from the hindquarters of
      sheep undergoing spinal anaesthesia. The method was used to measure the
      concentrations of lignocaine and bupivacaine in the blood, muscle and fat of the
      hindquarters of sheep during and after 180 min constant-rate infusions of the
      drugs. 2. For both drugs the muscle drug concentrations were a relatively
      constant ratio of the simultaneous arterial blood drug concentrations during and
      after the infusion. 3. There was uptake of both lignocaine and bupivacaine into
      subcutaneous fat during the infusions. At the end of the infusion the ratio of
      the fat: arterial blood drug concentrations were 1.54 (SD = 0.57, n = 4) and 3.1
      (SD = 1.4, n = 4) for lignocaine and bupivacaine, respectively. 4. The drug
      concentrations in fat declined relatively slowly after the infusion. The ratio of
      the fat: arterial blood drug concentrations 180 min after the end of the infusion
      was 21.5 (SD 4.0, n = 3) and for lignocaine, and 120 min after the end of the
      infusion was 9.54 (SD 5.2, n = 3) for bupivacaine. 5. It was concluded that the
      concentrations of lignocaine and bupivacaine in muscle were essentially in
      equilibrium with the arterial concentrations during and after the infusion.
      However, the concentrations of lignocaine and bupivacaine in fat were not in
      equilibrium with the arterial concentrations in the post-infusion period.

PMID- 2003364
TI  - The disposition of loxistatin and metabolites in normal and dystrophic hamsters.
AB  - 1. The absorption, distribution and excretion of loxistatin were studied in
      normal and dystrophic hamsters. 2. After oral administration of 14C-loxistatin to
      normal hamsters, the plasma level of radioactivity reached a maximum at 0.5 h and
      declined with an elimination half-life of 2.3 h. The ratios of metabolites M-1
      and M-4, which are pharmacologically active, to the total radioactivity in the
      plasma were 63% and 25% at 0.5 h after dosing, respectively. 3. After oral
      administration to hamsters, excretion of radioactivity in urine, faeces and
      expired air during 120 h were 64%, 28% and 6% of the dose, respectively. 4. The
      highest radioactivity was observed in kidney followed by liver. From the
      microautoradiographic study, radioactivity was found to be located in the cardiac
      and skeletal muscle fibre cells, which are target organs of the drug, in both
      dystrophic and normal hamsters.

PMID- 2003365
TI  - Metronidazole and antipyrine metabolism in the rat: clearance determination from
      one saliva sample.
AB  - 1. The applicability of a simple, non-invasive method for assessment of
      metronidazole and antipyrine metabolism in rats in vivo was investigated. 2. In
      48 sample pairs of blood and pilocarpine-stimulated saliva from six rats the
      concentration of metronidazole was almost identical (r = 0.97). 3. In 26 rats the
      clearance could be determined from one sample without loss of precision and
      accuracy compared with conventional determinations (r = 0.99). If urine was
      collected for 24 h the fractional clearance representing each elimination pathway
      could be determined. 4. Pretreatment with phenobarbitone increased the fractional
      clearance of metronidazole by oxidation and glucuronidation 3.8-fold and 1.6
      fold, respectively, whereas 3-methylcholanthrene pretreatment increased the rate
      of oxidation 10-fold and decreased the rate of glucuronidation 0.5-fold. 5. The
      clearance and fractional clearances of metronidazole and antipyrine administered
      in a mixture could be determined from the same saliva sample and urine collected
      for 24 h without drug-drug interactions. 6. Phenobarbitone pretreatment increased
      the formation rate of all metabolites of metronidazole and antipyrine
      administered in a mixture, whereas beta-naphthoflavone increased the formation
      rates of only the oxidative metronidazole metabolites, norantipyrine and 4
      hydroxyantipyrine, but not metronidazole glucuronide or 3
      hydroxymethylantipyrine. 7. A mixture of metronidazole and antipyrine and non
      invasive sampling are recommendable for the study of the differential metabolism
      of foreign compounds in rats in vivo.

PMID- 2003366
TI  - Structure determination of a diuretic-glutathione conjugate by mass and n.m.r.
      spectrometry.
AB  - 1. A glutathione (GSH) conjugate of the uricosuric diuretic DBCA 6,7-dichloro
      5(N,N-dimethylsulphamoyl)-2,3-dihydrobenzofuran-2-car boxylic acid, formed
      enzymically in rat liver 100,000g supernatant fortified with GSH, was purified by
      t.l.c. and h.p.l.c. 2. According to mass spectrometry the composition of the GSH
      conjugate corresponded to C21H29N4O11S2Cl2. 1H- and 13C-n.m.r. studies gave the
      structure of the conjugate as 2-glutathionyl-3-[3,4-dichloro-5-(N,N-dimethyl
      sulphamoyl)2-hydroxyphenyl]-propionic acid, which indicates that GSH was bound to
      the chiral centre carbon and caused scission of the C-O bond in the dihydrofuran
      ring.

PMID- 2003367
TI  - Metabolic interaction and disposition of methyl ethyl ketone and m-xylene in rats
      at single and repeated inhalation exposures.
AB  - 1. Rats were exposed to m-xylene (300 ppm) and methyl ethyl ketone (MEK, 600 ppm)
      vapour, separately and in combination. 2. Repeated exposures to m-xylene enhanced
      liver drug-metabolizing capacity, whereas MEK showed no effects. After mixed
      exposure the cytochrome P-450-dependent monooxygenase activities were additively
      or synergistically induced. 3. In the presence of MEK the overall metabolism of
      xylene was strongly inhibited both after single and repeated exposures, an effect
      accompanied by elevation of xylene concentration in blood (18-29%) and fat (25
      32%). 4. The 24-h excretion of the urine metabolites of m-xylene was decreased by
      22-24% in mixed exposures: the excretion of methylhippuric acid was decreased
      (29%), but that of 2,4-dimethylphenol increased (9-35%). 5. After repeated
      inhalation exposures the excretion of xylene metabolites in urine was
      consistently higher, whereas the concentrations of xylene in fat (but not the
      concentration of MEK) were lower than after a single treatment, conceivably due
      to accelerated metabolic clearance of xylene. 6. Thioether excretion in urine was
      enhanced in xylene-treated rats (7-13-fold), but was not influenced by the
      induced changes in the metabolism of xylene. Xylene inhalation caused liver GSH
      to decrease slightly (10%), as did inhalation of MEK, but the latter did not
      enhance the excretion of thioethers. 7. MEK is a potent inhibitor of the side
      chain oxidation of m-xylene producing methylhippuric acid, but not of its ring
      oxidation to 2,4-dimethylphenol, and exhibits a synergistic inducing effect on
      liver enzymes responsible for the oxidation of m-xylene. The increased ring
      oxidation of m-xylene was not associated with increased production of reactive
      metabolites indicated by GSH-depletion or thioether formation.

PMID- 2003368
TI  - Disposition of the toxic protein, bolesatine, in rats: its resistance to
      proteolytic enzymes.
AB  - 1. Bolesatine is a toxic protein (LD50 oral 3.3 mg/kg in mice) isolated from the
      mushroom Boletus satanas Lenz, which inhibits protein synthesis in vitro. It
      induces gastroenteritis in human. 2. 14C-Bolesatine, given orally to rats (30
      micrograms/kg), is distributed in the gastrointestinal, tract, kidney, liver and,
      to a lesser extent, in the thymus, spleen and lung. Bolesatine is eliminated in
      faeces and urine (80% in 24h). 3. The material excreted in urine is not
      proteolysed, and no protease (trypsin, chymotrypsin, pronase, proteinase K,
      Staphylococcus aureus (strain V8) protease and pepsin) is found to hydrolyse
      bolesatine in either its native or denatured form. However, thermolysin
      hydrolysed denatured bolesatine to a protein having a Mr of about 55 kD. 4.
      Bolesatine is found in all the following rat liver and kidney subcellular
      fractions: cytoplasm, mitochondria, ribosomes, microsomes and nuclei.

PMID- 2003369
TI  - Pharmacokinetics of the enantiomers of felodipine in the dog after oral and
      intravenous administration of a pseudoracemic mixture.
AB  - 1. A pseudoracemic mixture of deuterated (S)-felodipine and unlabelled (R)
      felodipine was administered as single i.v. or oral doses to four dogs. Plasma
      concentrations of the enantiomers and their corresponding pyridine metabolites
      were determined by g.l.c.-mass spectrometry. 2. No isotope effects were observed
      after oral administration of equimolar amounts of deuterated and unlabelled (S)
      felodipine. 3. The pharmacokinetic parameters of the enantiomers were similar
      after i.v. administration, indicating that the disposition of felodipine was not
      stereoselective. 4. After oral administration the bioavailability of (R)
      felodipine was slightly higher than that of (S)-felodipine in two of the dogs,
      presumably due to a lower first-pass extraction of the (R)-enantiomer, while no
      difference was observed in the other two dogs. 5. No substantial differences in
      Cmax or AUC were observed between the deuterated and unlabelled pyridine
      metabolites, indicating that the oxidative clearances of the felodipine
      enantiomers were similar.

PMID- 2003370
TI  - In situ intestinal absorption of 2-chloro-N-isopropylacetanilide (propachlor) and
      non-biliary excretion of metabolites into the intestinal tract of rats, pigs and
      chickens.
AB  - 1. Propachlor was absorbed from in situ intestinal loops of rats and pigs, with
      absorption half-times of 7.5 and 16.5 min, respectively. 2. Water-soluble 14C
      labelled metabolites that accumulated in the intestinal loops accounted for 31%,
      53%, and 25% of the starting 14C for rats, pigs and chickens, respectively. 3.
      Propachlor(S)cysteine was identified as the major metabolite in the pig
      intestinal lumen (43% of the water-soluble 14C). 4. It is concluded that
      intestinal metabolism and intestinal excretion of water-soluble metabolites of
      propachlor are important physiological processes that occur in a variety of
      animal species. These processes provide a route by which metabolites of
      xenobiotics may reach the intestinal lumen in animals which are poor biliary
      excretors.

PMID- 2003371
TI  - Metabolism of chlorpheniramine in rat and human by use of stable isotopes.
AB  - 1. The metabolism of chlorpheniramine (I) was examined in vivo in rats and a
      human volunteer; in the rats a stable isotope was used. 2. In addition to the
      unchanged drug (I) and the N-demethylated metabolites (II and III), nine further
      metabolites were identified in rat urine, four of which were also found in human
      urine. Chlorpheniramine N-oxide (IV), 3-(p-chlorophenyl)-3-(2-pyridyl) propanol
      (V), 3-(p-chlorophenyl)-3-(2-pyridyl)-N-acetylaminopropane (VII) and 3-(p
      chlorophenyl)-3-(2-pyridyl)-propionic acid (XIII) were identified in rat and
      human urine. 3. The hydroxylated metabolites of the pyridyl ring of the unchanged
      drug, II, V and VII, and the glucuronide of XIII were identified only in rat
      urine. XIII was found in rat urine as long as 6 days after the last dose.

PMID- 2003372
TI  - Growth hormone secretion patterns in relation to LH and estradiol secretion
      throughout normal female puberty.
AB  - Pulsatile growth hormone secretion patterns were studied in relation to
      luteinizing hormone and estradiol release in 33 healthy (pre)pubertal girls.
      Plasma GH was determined every 10 min, plasma LH and E2 every hour. Night-time GH
      release was always higher than daytime GH release. During daytime, all GH
      secretion parameters, except for the basal GH level, increased significantly from
      the prepubertal stage to stage B4 before (m-) the menarche (p = 0.05) and
      decreased thereafter (p = 0.05). During night-time, mean GH level and the
      fraction of GH in pulses also tended to increase from stage B1 to stage B4m-. The
      number of high pulses (greater than 8 micrograms/l) during day and night together
      tended to increase until stage B4m- and decreased after the menarche (p = 0.05).
      Height velocity did not correlate with the number of high pulses (Kendall tau =
      0.14, p = 0.14). From stage B1 to B4m- high correlations were observed between E2
      levels and GH secretion parameters, particularly during the day (tau = 0.59-0.71,
      p less than or equal to 0.01). The correlations between LH levels and GH
      secretion were high as well (tau = 0.50-0.81, p less than or equal to 0.01), but
      equal during day and night. It is concluded that during puberty 1. spontaneous GH
      release in girls increases 2-3 fold until the menarche and decreases thereafter,
      primarily as the result of an increasing and decreasing GH pulse amplitude; 2.
      diurnally increasing estradiol levels correlated with increasing GH secretion.

PMID- 2003373
TI  - Acupuncture in the treatment of Graves' ophthalmopathy. A blinded randomized
      study.
AB  - Seventeen patients with Graves' ophthalmopathy, all euthyroid for at least one
      year, were included in a blinded trial to test the effect of acupuncture twice a
      week during two months on the eye disease, assessed by an ophthalmologist and
      computed tomography of the eye muscle volume. No significant change was found in
      eye muscle volume, Hertel measure, palpebral aperture, intraocular pressure, Hess
      chart, nor was there any statistically significant improvement of the irritative
      conjunctival symptoms.

PMID- 2003374
TI  - Hyperthyroidism and thyroid carcinoma.
AB  - Twenty-two of 251 patients with differentiated thyroid carcinoma suffered from or
      had a history of hyperthyroidism. They were hyperthyroid with a diffuse goitre (N
      = 4), a diffuse goitre with a cold nodule (N = 10), a multinodular goitre (N =
      6), and an autonomous adenoma (N = 2). Among the 22 patients, more than one
      fourth had an occult thyroid carcinoma with a diameter of 1 cm or less, those
      with the papillary tumour types, less frequently had lymph node metastases than
      the total group of patients with papillary carcinomas (13.3 vs 35.6%). The
      clinical courses of the 22 patients resembled those of the other thyroid
      carcinoma patients whose age and initial findings were comparable. In 643
      patients who underwent surgery for hyperthyroidism the incidence of thyroid
      carcinoma was 2.3%. The increase in coincidence of hyperthyroidism and thyroid
      carcinoma repeatedly reported in recent years is probably ascribable primarily to
      extensive and improved diagnostics and not to a direct connection between
      hyperthyroidism and development of thyroid carcinoma. On the other hand, our
      findings do confirm that, even in the presence of hyperthyroidism, all thyroid
      nodules require careful diagnostics for exclusion of malignancy.

PMID- 2003375
TI  - Persistence of altered metabolic responses to beta-endorphin after normalization
      of body weight in human obesity.
AB  - The responses of plasma glucose, insulin, C-peptide and glucagon to an infusion
      of human beta-endorphin (0.5 mg/h) were studied in 10 formerly obese subjects who
      had lost 35 kg by dieting (body mass index less than 25) and compared with those
      of 10 normal-weight control (body mass index less than 25) and 10 obese (body
      mass index greater than 30) subjects. The fasting plasma concentrations of beta
      endorphin were significantly higher in both the obese and the post-obese group
      than in the control group. In both obese and post-obese subjects, the infusion of
      beta-endorphin caused significant increases in peripheral plasma glucose,
      insulin, C-peptide and glucagon concentrations. In the control group, matched for
      age, sex and weight with the formerly obese group, there was no appreciable
      change in plasma insulin and C-peptide concentrations during the infusion of beta
      endorphin, but the rise in plasma glucose was more sustained. Thus, 1. the
      increased plasma beta-endorphin concentrations found in human obesity are not
      corrected by normalization of body weight; and 2. formerly obese, normal-weight
      subjects behave as obese subjects in their metabolic and hormonal responses to
      beta-endorphin infusion. The alteration of the opioid system in human obesity may
      play some role in the predisposition to weight gain.

PMID- 2003376
TI  - Transient increase in renal epidermal growth factor content after unilateral
      nephrectomy in the mouse.
AB  - A sensitive enzyme-linked immunosorbent assay for mouse epidermal growth factor
      was established for measurement of the content of epidermal growth factor in the
      remaining kidney after uninephrectomy. In 5-week-old male mice, the renal
      epidermal growth factor content before uninephrectomy was 355 +/- 97 ng/g wet
      tissue with a 2.1-fold increase on the first day after uninephrectomy, whereafter
      it gradually decreased. In 15-week-old mature male mice, the renal epidermal
      growth factor content increased 1.7-fold on the first day after uninephrectomy.
      Immunohistochemical analysis showed that epidermal growth factor was present in
      the distal tubular cells and that the staining intensity was increased on the
      first day after uninephrectomy. During the course of compensatory renal growth,
      no significant alteration of epidermal growth factor content was observed in
      plasma or in the submaxillary gland. Our data suggest that the increase in renal
      epidermal growth factor content after uninephrectomy is due to an increased
      production of epidermal growth factor in the kidney itself. The significance of
      this phenomenon is discussed.

PMID- 2003377
TI  - Objective assessment of concordance of secretory events in two endocrine time
      series.
AB  - A new objective method is presented for investigating the presence of a temporal
      relationship between episodic release of two hormones. The two time series of
      hormone concentrations are first analysed by an objective method for peak
      detection. Both data series are then transformed into "quantized" or discretized
      series by recording the occurrence of a hormone pulse as an "event",
      characterized by the onset, the maximum, or another unique feature. The two
      quantized series are then matched, and the number of concordant events and
      discordant events are counted. Each point in series A is compared with a "time
      window" of a selected number of points in series B, to accommodate small degree
      of mismatch between events in the two series. An index of concordance is
      computed, compensating for any spurious random coincidence: the "Specific
      Concordance", to evaluate the frequency of concordant events in excess of those
      expected on the basis of chance alone. This calculation is systematically
      repeated, interposing a range of time-lags between the two series. A graph of
      Specific Concordance versus time-lag indicates the time-lag corresponding to a
      maximal concordance. Simulations of random series of events are performed, and
      their degree of concordance is evaluated in a similar fashion, thus generating
      frequency distributions of Specific Concordance values under the null hypothesis
      of no temporal relationship. This permits the selection of criteria for
      statistical significance at any desired p-level, for one or many lag times, and
      for one or multiple subjects. Various degrees of concurdance can also be
      stimulated to evaluate the performance (sensitivity, statistical power) of this
      approach. These methods have been implemented as a collection of short
      microcomputer programmes, and applied to the study of the temporal relationship
      between beta-endorphin and cortisol in normal subjects sampled every 10 min for
      24 h. This analysis demonstrated concordance between events in the two series,
      with synchronous occurrence of beta-endorphin and cortisol release events
      significantly more frequently than expected on the basis of random association (p
      less than 0.01).

PMID- 2003378
TI  - Urine steroid excretion rates in childhood reflect growth and activity of the
      adrenal cortex.
AB  - Normal ranges for daily urine steroid excretion rates in childhood are reported
      for the first time by gas chromatographic analysis using capillary columns and
      flame ionisation detector. Longitudinal data came from a study over 3 years of
      127 normal boys (aged 7.5-15.6 years) studied on 5 occasions and 14 pubertal
      girls studied over 2 years. Cross-sectional data were collected from 115
      hospitalized patients (58 males, 57 females) aged 2.9 to 14 years with normal
      adrenal function. The excretion rate of cortisol metabolites was constant for
      body size, whereas androgen metabolite excretion rates rose sharply in childhood
      to approach adult levels at the end of puberty. The new data will enable better
      interpretation of pediatric patient data.

PMID- 2003379
TI  - Polyethylene failure of metal-backed patellar components. 111 AGC total knees
      followed for 7-22 months.
AB  - In a series of 111 AGC total knee arthroplasties, eight failures of the
      polyethylene part of the metal-backed patellar component were seen after a period
      of 7-22 months. All of these patients experienced a characteristic grating sound
      as the knee was bent, and skyline radiographs revealed direct metal-on-metal
      contact. At revision, fracture and separation of the polyethylene part were found
      together with an extensive, black, thickened synovium and abrasive wear of the
      naked metal backing of the patellar component. The cemented metal backings were
      all solidly anchored in the patella. Based on this high failure rate, we have
      abandoned the metal-backed patellar component in favor of an all-polyethylene
      component.

PMID- 2003380
TI  - Surface flatness after bone cutting. A cadaver study of tibial condyles.
AB  - A methodologic study with which the cut surface could be quantified was performed
      on cadaveric tibial bone prepared for endoprosthetic components. Using
      sterilized, dental-imprint material and measuring with a Zeiss UMC 850, the
      characteristics of the cut surface were defined. A clinically flat surface was
      found to be uneven, with a maximum roughness between the uppermost and lowermost
      points of 1.0 and 2.4 mm for the bone surface and between 1.2 and 2.3 mm for the
      imprint. The flatness, defined as the standard deviation of the measuring points,
      was between 0.15 and 0.40 mm for the bone and 0.20 and 0.42 mm for the imprint.
      This lack of flatness creates gaps between the prosthesis and the bone.

PMID- 2003381
TI  - Osteonecrosis of the knee. Diagnosis and outcome in 40 patients.
AB  - Clinically suspected primary osteonecrosis of the knee was studied in 40 patients
      with repeated plain radiography and scintimetry, and the patients were followed
      for 1-7 years. Thirty-three patients had typical scintimetric and radiographic
      signs of osteonecrosis of either one of the femoral condyles, whereas 7 patients
      had only typical scintimetric findings, but never developed an osteonecrosis
      based on plain radiography. Because the scintimetric findings were identical to
      the other 33 knees and because there is no other well-known localized disease in
      this region of the femoral condyle, we deemed that these 7 patients had probable
      osteonecrosis, but in an abortive form. The scintimetries were prognostic during
      the second half year after onset. Thirty knees had a poor outcome--29 because of
      development of arthrosis, of which eight were treated with a knee arthroplasty
      and four with a proximal osteotomy.

PMID- 2003382
TI  - Delayed contact hypersensitivity and surgical glove penetration with acrylic bone
      cements.
AB  - Skin hypersensitivity was investigated in guinea-pig maximization tests with
      extracts from pellets of conventional polymethyl-methacrylate (PMMA) bone cements
      (Palacos R, Simplex RO) and a new methylmethacrylate/n
      decylmethacrylate/isobornylmethacrylate (MMA/DMA/IBMA) mixture (Boneloc), but
      none of the three cements produced evidence of delayed contact hypersensitivity.
      Testings of the pure monomer compounds showed MMA to be an extreme sensitizer,
      whereas DMA and IBMA were only mild sensitizers. Fingers from three brands of
      surgical rubber gloves and a polystyrene-butadiene glove were immersed in water
      and filled with conventional MMA monomer, MMA/DMA/IBMA monomer or bone cements in
      the dough state, allowing cure inside the glove. In the surrounding water, no DMA
      or IBMA could be detected. The MMA concentrations were lower with MMA/DMA/IBMA
      monomer and curing Boneloc cement. The most resistant to conventional PMMA cement
      was one of the rubber gloves, whereas the polystyrene-butadiene glove allowed the
      highest penetration, and even dissolved in MMA monomer. The potential
      occupational hazard of skin sensitization is reduced with MMA/DMA/IBMA bone
      cement, preferably in combination with rubber gloves; but also polystyrene
      butadiene gloves provide adequate protection.

PMID- 2003383
TI  - Lack of immune response to methyl methacrylate in lymphocyte cultures.
AB  - To analyze whether or not methyl methacrylate is immunologically inert,
      peripheral blood mononuclear cells were cultured with finely pulverized methyl
      methacrylate. Phytohemagglutinin (PHA) lectin, purified protein derivate of
      tuberculin (PPD) antigen, and culture medium alone were used as positive and
      negative controls. Lymphocyte kinetics on culture Days 0, 1, 3, and 5 were
      studied. Major histocompatibility complex locus II antigen (MHC locus II antigen;
      Ia) and interleukin-2 receptor (IL-2R; Tac) expression were analyzed using the
      avidin-biotin-peroxidase complex (ABC) method and lymphocyte DNA synthesis using
      3H-thymidine incorporation and beta-scintillation counting. On culture Days 1 and
      3, lymphocytes and monocytes were seen under the light microscope to be attached
      to methyl methacrylate particles. However, the results disclosed no methyl
      methacrylate-induced DNA synthesis, although methyl methacrylate-induced MHC
      locus II antigen and IL-2R activation marker expression were recorded; notably,
      this expression was less pronounced than that seen in PHA or PPD antigen driven
      lymphocyte response. The results suggest that methyl methacrylate is essentially
      an immunologically inert implant material. However, it seems to induce
      inflammatory mononuclear cell migration and adhesions leading to slightly
      nonspecific lymphocyte reaction.

PMID- 2003384
TI  - Costs of hip fracture. Rehabilitation of 180 patients in primary health care.
AB  - Costs related to functional status were calculated for 180 consecutive hip
      fracture patients (mean age 78 years) who were admitted from their own home and
      rehabilitated in primary health care. Within 4 months after the fracture, 75
      percent of the patients had been discharged to their own home, 9 percent were
      dead, and the short-term medical treatment costs per patient were SEK 43,000,
      whereas the total costs including communal help and costs for living
      accommodations after discharge were twice as high. The total costs per patient
      for long-term medical treatment (from 4 months up to 3 years after fracture) were
      7 percent of the short-term medical treatment costs. Patients with a cervical
      fracture discharged to their own home and with good functional status consumed
      only one fifth of the resources that patients with a trochanteric fracture
      discharged to institutional care and who had reduced functional status consumed.
      A substantial part of the costs can be saved by improved organization of
      rehabilitation after discharge from the hospital. A further cost reduction would
      require a combination of technologic, social, and organizational changes aimed at
      early discharge and continued follow-up in primary health care.

PMID- 2003385
TI  - Anterolateral instability in the anterior cruciate ligament deficient knee. A
      cadaver study.
AB  - Knee instability was evaluated in 13 normal osteoligamentous knee preparations
      after transection of the anterior cruciate ligament. Abduction-adduction
      rotation, coupled tibial translatory movement, and coupled tibial axial rotation
      were recorded continuously and simultaneously during flexion or extension while
      applying a well defined valgus directed moment and during extension while
      applying an anterior tibial force. As a result of the valgus-directed moment, an
      increase was found in abduction rotation, in coupled anterior tibial translation,
      and in coupled internal tibial axial rotation. Coupled rotatory and translatory
      instabilities were larger, and maximum instability was observed at a smaller knee
      angle during the extension movement than during the flexion movement. The pattern
      of the instability, excited as a result of the valgus moment, was different from
      the instability excited as a result of an anterior tibial force.

PMID- 2003386
TI  - Effect of platelet derived growth factor on heterotopic bone formation in rats.
AB  - Platelet derived growth factor (PDGF) and induction of newly woven bone growth
      were studied in rats. PDGF (20 ng/mL) was administered continuously for 2 weeks
      via micro-osmotic pumps to 6-mm-long pieces of demineralized rat femur inserted
      into muscle pouches. Each rat had a control piece of demineralized bone inserted
      into the contralateral gluteal muscle. The samples were collected after 4 weeks,
      and wet and ash weight were recorded. Fourteen rats were evaluated. There were no
      differences as regards wet weights. PDGF increased the ash weights.

PMID- 2003387
TI  - Souter-Strathclyde arthroplasty of the rheumatoid elbow. 23 cases followed for 3
      years.
AB  - Twenty-three elbows in 17 rheumatoid arthritis patients have undergone
      unconstrained Souter-Strathclyde elbow replacements since March 1984. One patient
      developed a deep-wound infection, and 4 others had a temporary ulnar nerve
      paresis. At follow-up 3 (0.5-6) years postoperatively, there was a moderate
      improvement in the arc of movements: 25 degrees in extension-flexion and 45
      degrees in forearm rotation. Pain relief was achieved in 20 cases. Three elbows
      required revision, two following recurrent dislocation and the other after a
      humeral fracture and component loosening.

PMID- 2003388
TI  - Staple fixation of osteotomy for cubitus varus. A simple technique used in 11
      children.
AB  - Eleven children with a persistent varus deformity of 15 degrees or more were
      operated on with a supracondylar lateral closing-wedge osteotomy. The osteotomy
      was stabilized with a staple after predrilling for the legs of the staple. No
      displacement occurred in the osteotomy. The results were excellent in all the
      cases.

PMID- 2003389
TI  - Tension-band fixation of olecranon fractures. A cadaver study of elbow extension.
AB  - The loss of extension produced by tension-band wiring was studied using cadaveric
      elbows. Extension loss was found to be due to impingement of the longitudinal
      wires against the humerus independent of the tension band. Reducing the size of
      the bent end of the longitudinal wire is recommended, and bending the wire into a
      loop achieves this. In addition, passing the tension band through the loops
      prevents the wire from backing out.

PMID- 2003390
TI  - The AO-plate for external fixation in 12 cases.
AB  - The AO-plate was used for external fixation in 12 patients. The main indications
      were severe open fractures of the forearm and infected pseudarthroses at several
      locations. In 10 cases, the fixation provided enough stability to allow bone
      healing. The technique is simple, is convenient for the patient, and is always
      available without additional special equipment.

PMID- 2003392
TI  - Effect of physical activity on muscle and bone blood flow after fracture.
      Exercise and tenotomy studied in rats.
AB  - In male Wistar rats, a transverse osteotomy of the midshaft of the left femur was
      performed. The rats were allocated to three groups: 1) one that underwent a 4
      week training program 4 weeks after the osteotomy, 2) one that had a tenotomy of
      the left Achilles tendon to prevent weight bearing, and 3) one that had normal
      function and activity. Eight weeks after the osteotomy, total bone, proximal
      diaphyseal, callus, and muscle blood flows were measured using the microsphere
      technique. Initial and final body weight, bone weight, and callus production were
      also recorded. There were no differences in bone or muscle blood flow between the
      three groups. An increase in total bone and muscle blood flows was seen on the
      osteotomized side. In weight-bearing rats, the callus area was more vascular as
      compared with the diaphyseal bone. No correlation between callus mass and callus
      flow was found. Our results support the concept that blood supply is mandatory
      for fracture healing; however, other factors seem to be decisive for the rate of
      healing.

PMID- 2003391
TI  - Metatarsal head excision for rheumatoid arthritis. 4-year follow-up of 68 feet
      with and without hallux fusion.
AB  - Thirty-four painful deformed rheumatoid feet treated by excision of all five
      metatarsal heads were compared with 34 similar feet in which the lesser
      metatarsal heads were excised and the first metatarsophalangeal joint was
      arthrodesed. In the latter group, one third had failure of fusion of the hallux,
      and this produced the worst results. Metatarsalgia and plantar callosities were
      more common after excision arthroplasty, but shoe fitting and correction of
      deformity were better in this group. However, the results were more variable in
      the fusion group, and the complication and reoperation rates were higher. For
      this reason, excision arthroplasty, rather than fusion of the hallux, is
      recommended when the lesser metatarsal heads are removed.

PMID- 2003393
TI  - Cord compression in Scheuermann's kyphosis. A case report.

PMID- 2003394
TI  - Osteolysis after ceramic-on-ceramic hip arthroplasty. A case report.
AB  - A patient with rheumatoid arthritis operated on with insertion of an uncemented
      ceramic-on-ceramic Mittelmeier total hip developed an extensive, rapidly evolving
      osteolysis around the prosthetic stem, which in turn fractured spontaneously
      after 5 years. Aggressive bone resorption cannot be prevented by exclusion of
      polyethylene and bone cement from hip arthroplasty.

PMID- 2003395
TI  - Chondrosarcoma from a rib metastasizing to the ovary.

PMID- 2003396
TI  - Volar compartment syndrome of the arm complicating a fracture of the humeral
      shaft. A case report.

PMID- 2003397
TI  - A case of tuberculosis of the scapula.

PMID- 2003398
TI  - Two cases of shoulder joint tuberculosis.

PMID- 2003400
TI  - Neurobiological substrates of ictal behavioral changes.

PMID- 2003399
TI  - Muscle coordination following rupture of the anterior cruciate ligament.
      Electromyographic studies of 14 patients.
AB  - In an electromyographic (EMG) study, the coordination in muscles acting on the
      knee joint was assessed in 14 patients with an arthroscopically verified complete
      rupture of the anterior cruciate ligament and in 16 controls. EMG and heel
      contact signals were recorded while walking on a treadmill at walking gradients
      from 0 to 25 percent. There was an earlier onset of EMG bursts in the patients,
      especially in the lateral hamstrings and medial gastrocnemius; and the duration
      of EMG bursts also tended to be prolonged in the patients. Normalized root mean
      squares of amplitudes, which correlate with muscle tension, were higher in the
      gastrocnemius in the patients. EMG profiles, outlining the averaged muscle
      activity throughout the gait cycle, showed a displacement of peak activity in the
      hamstrings from the late swing phase into the stance phase, with increasing
      gradients in both the patients and the controls. Our study indicates that the
      gastrocnemius muscle contributes to functional stability in the anterior cruciate
      ligament deficient knee, and more attention should be paid to this muscle.

PMID- 2003401
TI  - Behavioral correlates of interictal spikes.

PMID- 2003402
TI  - Acute behavioral symptomatology at disappearance of epileptiform EEG abnormality.
      Paradoxical or "forced" normalization.
AB  - Paradoxical or "forced" normalization of the EEG of patients with epilepsy was
      first described by Landolt in 1953. It refers to conditions where disappearance
      of epileptiform discharge from the routine scalp EEG is accompanied by some kind
      of behavioral disorder. The best known of these is a paranoid psychotic state in
      clear consciousness, which is also known as "alternative" psychosis. Thus, the
      issue is related to much older observations which indicated a "biological
      antagonism" between productive psychotic symptomatology and epileptic seizures,
      which led to the therapy of psychoses with artificially induced convulsions.
      Apart from psychotic episodes, the clinical manifestations of PN comprise
      dysphoric states, hysterical and hypochondriacal syndromes, affective disorders,
      and miscellanea. PN can be observed in both generalized and localization-related
      epilepsies as a rare complication. A subset where it is more frequently seen are
      in adults with persistent absence seizures when the latter become finally
      controlled by succinimide therapy. These seem to be the drugs with the highest
      hazard of precipitation of PN, but all other AEDs have also been suspected. Sleep
      disturbance by succinimide treatment may play a crucial role, but a variety of
      other factors are also involved, including psychosocial factors. The pathogenesis
      of this condition has given rise to some debate but remains still unresolved.
      Eleven of the most important hypotheses have been discussed and seem to converge
      into a more comprehensive hypothesis which basically assumes that, during PN, the
      epilepsy is still active subcortically, perhaps with spread of discharge along
      unusual pathways. This activity is supposed to provide energy and, possibly, some
      of the symptoms included in the psychotic syndrome. A critical clinical condition
      results, usually with a dysphoric symptomatology, where a development towards
      psychosis is impending but still depends on the presence or absence of a variety
      of risk factors. Along with neurophysiological factors such as powerful
      inhibition of the spread of epileptic discharge, these may also include
      biographic factors such as the repeated experience of ictal sudden, unexpected
      loss of consciousness. Because during PN there presumably is ongoing epileptic
      activity, the differences with respect to other psychotic conditions in epilepsy
      are probably subtle rather than fundamental. Thus, it could be that ictal
      psychosis is characterized by a direct expression of epileptic activity, whereas
      in postictal psychosis a momentum of exhaustion may be added; moreover, in PN the
      prevailing pathogenic factor could be an abnormally high level of balance between
      excitatory and inhibitory processes.

PMID- 2003403
TI  - Interictal psychoses of epilepsy.

PMID- 2003404
TI  - Behavioral consequences of epilepsy in children. Developing a psychosocial
      vocabulary.
AB  - In this chapter we have described some of the experiences of a special
      psychiatric clinic for children with epilepsy, drawing our examples from a series
      of 50 children. The behavioral consequences of epilepsy cannot be adequately
      described within the limited nosology available for classifying the behavior
      disorders of children. As an alternative, a series of behaviors which children
      actually require in order to maintain their social existence have been
      identified; furthermore, impairments of those behaviors have been pointed to, and
      consequences of these behavioral impairments have been outlined. The behavioral
      consequences of epilepsy are often multiple and are sometimes mutually
      interactive. The extent to which these behavioral deviations depend both upon the
      exhibition of seizures and the presence of structural abnormalities in the brain
      is made most evident by the marked changes in behavior which can be achieved when
      epilepsy is relieved and a lesion is removed. Unfortunately, such a stratagem is
      not available to the majority of children with epilepsy. For the time being,
      their cerebral impairment and the continuation of their epilepsy have to be taken
      for granted, and intervention then consists of the best possible management of
      their impairments and their distressing behaviors. Such management clearly
      requires psychiatric and psychological skills, although these skills do not
      necessarily lead to greater success than does the use of anticonvulsants or the
      use of surgery. Success is not an adequate measure of the appropriateness of the
      endeavor. It goes without saying that not all children with epilepsy suffer
      behavioral consequences along these lines, and indeed behavioral disturbances
      were not universal even in this highly selected series. Some children were seen
      merely as a way of improving their medical status or achieving surgical
      treatment. These more traditional medical maneuvers are easier to undertake and
      are more understandable to parents than are complex strategies of psychiatry. In
      any event, parents deserve considerable support. The language of psychiatry for
      children with organic cerebral impairments is extremely limited; this chapter has
      been an attempt to improve our vocabulary, which will be a necessary underpinning
      in order to improve the quality of our classification. Finally, we return to
      Bridge's statement. Firstly, we do not regard epilepsy as a disease any more than
      we would regard cough as a disease, and we find that orientations in that
      direction are likely to thwart our attempt at piece-by-piece dismantling of the
      many sorts of disease which might be associated with seizures.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 2003405
TI  - Evocation and inhibition of seizures. Behavioral treatment.
AB  - These behavioral studies provide abundant evidence of the close interrelation
      between seizure activity and behavior. They reaffirm the point already made
      several times in this chapter: Seizures do not occur in a behavioral vacuum. They
      also strengthen the theoretical framework which provides for behavioral treatment
      of patients with epilepsy. With the detailed knowledge that we now have of the
      epilepsy focus and the way that it is connected to the surrounding cerebral
      mechanisms, it really is not surprising that seizure control is significantly
      influenced by altering the outlook and behavior of the patient with epilepsy.
      Seizures should not be thought of as arising randomly. They occur, in the case of
      focal seizures, when the pools of group 2 neurons are sufficiently excited for
      seizure activity to spread. Generalized seizures occur when the level of cortical
      excitability or of corticoreticular excitation has reached a point at which
      thalamic recruiting volleys generalize and start to spread. In the case of the
      focal epilepsies, a detailed clinical history should be taken as to the nature
      and characteristics of the aura; the history should also include details
      regarding the form that the seizure generalization or spread may take. This
      information allows the accurate location of the seizure focus, as well as of the
      cerebral structures through which the seizure discharge passes. The position of
      the focus will determine the relationship between the individual and his
      epilepsy. It will define those aspects of the psychic life or behavior of a
      patient which will both trigger and inhibit seizure activity. Detailed discussion
      of this information with the patient will help him to understand that his
      seizures are not part of a random process but are, instead, intimately related to
      how he feels, what he is doing, and what he is thinking. A complete treatment of
      epilepsy is not just the administration of drugs; rather, it also includes (a)
      teaching the patient about his brain and its functioning and (b) how the
      patient's feelings, thinking, and behavior can all be used in the control of his
      epilepsy.

PMID- 2003406
TI  - Epilepsy and disorders of mood.

PMID- 2003407
TI  - Cognitive effects of antiepileptic drugs.

PMID- 2003408
TI  - Behavioral effects of antiepileptic drugs.

PMID- 2003409
TI  - Effects of antiepileptic drugs on the developing central nervous system.

PMID- 2003410
TI  - Antiepileptic drugs in affective illness. Clinical and theoretical implications.

PMID- 2003411
TI  - Effects of temporal lobe surgery on behavior.

PMID- 2003412
TI  - Behavioral changes following corpus callosotomy.

PMID- 2003413
TI  - Ictal manifestations of temporal lobe seizures.

PMID- 2003414
TI  - Psychobiology of ictal aggression.
AB  - 1. Aggression in animals has been classified into a number of stereotyped
      behavioral responses on the basis of the psychosocial environment in which it
      occurs. Many such responses can be either replicated or blocked by stimulation or
      ablation of selected sites in the brain, especially in the hypothalamus or
      amygdala. Stimulation of the amygdala or the hypothalamus in a limited number of
      humans has produced agitation, anger, or rage. Ablation of the amygdala has
      reduced aggression in violent patients. However, the ictal nature of episodic
      aggression in these patients has not been proven. 2. The diagnosis and
      classification of epileptic seizures is based on their characteristic clinical
      manifestations and electrical patterns. Independent objective markers of ictal
      events need to be identified. Epileptic seizures are characterized by stereotyped
      nondirected behavior, especially at onset. The more organized, directed, and
      modifiable by the environment the behavior is, the less likely it is epilepsy. 3.
      Ictal aggression can be classified into primary and secondary ictal aggression,
      resistive violence, and postictal psychosis. Few alleged cases of ictal violence
      or aggression fulfill criteria for ictal events; most which do are examples of
      resistive violence. 4. If animal models can be developed which exhibit
      spontaneous paroxysmal stereotypical aggression, they may be used to improve our
      understanding of the classification and pathophysiology of ictal aggression.

PMID- 2003415
TI  - Ictal amnesia and fugue states.

PMID- 2003416
TI  - Memory function in patients with epilepsy.

PMID- 2003417
TI  - Memory dysfunction in epilepsy patients as a derangement of normal physiology.
AB  - Patients with CPS often display recent memory deficits. Typically, general
      intelligence, perceptual skills, language, remote memory, and primary memory are
      all normal. However, the ability to learn new combinations of cognitively complex
      material is deficient. This deficit may be specific for verbal material (e.g., as
      a difficulty with learning to recall a response word given an unrelated cue
      word), for nonverbal material (e.g., as a difficulty in drawing a complex figure
      from memory), or for both verbal and nonverbal material. Because these
      characteristics are typical of memory deficits after MTL damage, it is reasonable
      to suspect that these deficits in patients with epilepsy also reflect MTL damage.
      In many cases, MTL damage is apparent from neuroimaging studies, whereas seizure
      semiology suggests MTL onset. In these patients, the same pathology might be the
      cause of both the ictus and memory deficits. In other cases, memory impairment
      appears to be secondary to seizures. This suggestion is supported by cases where
      prolonged complex partial status resulted in a permanent global amnesia. Cases
      with shorter-lasting memory deficits were also presented. Neuropsychological
      testing revealed specific recent-memory deficits that cleared 2 weeks after a
      flurry of CPS and 24 hr after a single seizure. Depth recordings have
      demonstrated that MTL electrographic seizures can occur without subjective
      manifestations. When these are evoked by local electrical stimulation, a profound
      inability to learn new material may be observed during the afterdischarge.
      Similarly, artificially induced MTL spike-and-wave complexes interfere with the
      memory for simultaneously presented complex visual scenes. Recent evidence
      suggests that all of the above phenomena may reflect the engagement by
      epileptiform processes of the association-cortex (AC)-MTL circuits used in normal
      human memory. In recent memory tasks, cognitive evoked-potential components N4
      and P3 are generated in the MTL and to a lesser degree in related AC regions. The
      N4/P3 are strongly modulated by familiarity in recent memory. This modulation is
      eliminated by anterior temporal lobectomy. The typical slow wave following
      spontaneous MTL interictal spikes has the same MTL voltage topography, and thus
      probably similar synaptic generators, as the cognitive P3 potential. Furthermore,
      MTL spike-and-wave complexes can be evoked in recent memory tasks at a fixed
      latency equal to that of the N4.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 2003418
TI  - The Geschwind syndrome.
AB  - A characteristic personality syndrome consisting of circumstantiality (excessive
      verbal output, stickiness, hypergraphia), altered sexuality (usually
      hyposexuality), and intensified mental life (deepened cognitive and emotional
      responses) is present in some epilepsy patients. For identification, the term
      "Geschwind syndrome" has been suggested as a name for this group of behavioral
      phenomena. Support for, and criticism against, the existence of this syndrome as
      a specific personality disorder has produced more fire than substance, but the
      presence of an unsettled, ongoing controversy has been acknowledged. At present,
      the strongest support stems from the many clinicians who have described and
      attempted to manage seizure patients with these personality features. Carefully
      directed studies are needed to confirm or deny that the Geschwind syndrome
      represents a specific epilepsy/psychiatric disorder.

PMID- 2003419
TI  - Modern approaches to neuropsychological testing.

PMID- 2003420
TI  - Neurobiological, psychosocial, and pharmacological factors underlying interictal
      psychopathology in epilepsy.

PMID- 2003421
TI  - Emotional effects on seizure occurrence.
AB  - Emotional factors can alter the likelihood of seizure occurrence, and they
      usually increase the frequency of attacks. Our case studies showed that such
      activation is brought about through missed medication, sleep deprivation, and
      hyperventilation. Less well documented is the possibility that increased
      excitability and seizures may be due to direct neuronal activation of limbic
      circuits, although such a mechanism would be quite plausible.

PMID- 2003422
TI  - Legal implications of behavioral changes in epilepsy.

PMID- 2003423
TI  - Interictal psychiatric disorders. Neurochemical aspects.

PMID- 2003424
TI  - Are complex partial seizures a sequela of temporal lobe dysgenesis?
AB  - 1. Complex partial seizures are closely associated with a group of discrete
      neuropathological entities which include focal lesions (such as hamartomas and
      heterotopias) and small vascular lesions, all of which are generally considered
      to have been present at birth. 2. The pathological change most frequently found
      in patients with temporal lobe epilepsy is mesiotemporal sclerosis. Although this
      pathological alteration in subicular and hippocampal structures has been
      attributed to any one of a number of perinatal or postnatal insults, we suggest
      that it also may represent a sequela of disturbed neuroembryogenesis. 3. We
      suggest that many, perhaps most, cases of temporal lobe epilepsy may resemble
      other major disorders of cognition and behavior (such as schizophrenia) in
      representing the sequelae of temporal lobe dysgenesis.

PMID- 2003425
TI  - Psychosis and the temporal lobe.

PMID- 2003426
TI  - Neurobiological evidence for epilepsy-induced interictal disturbances.
AB  - It is not in the best interest of persons with epilepsy to deny the possibility
      that seizures could cause enduring behavioral disturbances. Rather, it is
      essential to pursue clinical and animal investigations in order to identify any
      such changes that might occur and to elucidate their mechanisms. Many testable
      hypotheses can be developed from existing evidence. Antiepileptic medication may
      produce interictal behavioral disturbances in patients with epilepsy by indirect
      mechanisms. Some aberrant behaviors could be due to medication-induced systemic
      disorders, neuroendocrine dysfunction, or REM deficit, whereas depression
      following successful treatment with drugs, as well as with surgery, may be
      related more specifically to cessation of seizures. The underlying
      neuropathological process also induces neurological and mental deficits, but it
      is not always possible to differentiate those behavioral disturbances due to
      destructive effects of the lesion from those due to recurrent epileptic seizures.
      Behavioral disturbances are associated more frequently with epileptogenic lesions
      in limbic structures than with those elsewhere in the brain, but a relationship
      between hemispheric lateralization of the epileptogenic lesion and specific
      interictal behavioral symptoms remains controversial. When considering the
      effects of seizures per se on interictal behavior, it is important to realize
      that some "interictal" behavioral disturbances may actually be ictal events.
      Prolonged affective, autonomic, and psychic disturbances can occur in clear
      consciousness with unilateral limbic seizures that are not associated with scalp
      EEG changes. When epilepsy is acquired as a result of cerebral damage, the
      epileptogenic process takes time to develop before spontaneous seizures appear.
      It is more reasonable to assume that this progressive process continues than to
      postulate that it stops completely at the time the first seizure occurs. Epilepsy
      induced protective homeostatic mechanisms that act to terminate ictal events,
      prevent ictal spread, and maintain the interictal state may also disrupt
      interictal function. Furthermore, seizures could indirectly influence interictal
      behavior as a result of their effects on neuroendocrine function and sleep.
      Because of confounding biological factors, it is difficult to document the
      association of any epilepsy disorder, by itself, with progressive behavioral
      disturbances in humans. Secondary epileptogenesis, protective homeostatic
      mechanisms, and epilepsy-induced disturbances in development can be readily
      demonstrated, however, in experimental animal models. In experimental animals,
      endogenous opoids are released during seizures and mediate some postictal
      behaviors. A physiological dependency on high levels of endogenous opioids
      released during seizures could produce depression as a withdrawal symptom
      interictally or when seizures no longer occur as a result of successful therapy.
      Experimental animal models of depression exist to test hypotheses concerning pro-
      and antidepressant effects of epileptogenesis.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 2003427
TI  - Fleischner lecture. Developmental abnormalities in the systemic blood supply to
      the lungs.
AB  - Developmental abnormalities in the systemic blood supply to the lungs occur in
      association with congenital heart disease, congenital lung disease, and rarely
      with apparently normal heart and lungs. Although most of these anomalies are
      rare, in the aggregate they are relatively common and of special interest to
      students of chest and heart disease.

PMID- 2003428
TI  - Edward B.D. Neuhauser memorial lecture. Bronchopulmonary dysplasia and research
      in diagnostic radiology.

PMID- 2003429
TI  - Chest CT combined with artificial pneumothorax: value in determining origin and
      extent of tumor.
AB  - To determine the presence of chest wall and mediastinal invasion by lung cancer
      and to establish the origin of chest tumors, we studied 12 patients with
      intrathoracic tumors by using chest CT combined with artificial pneumothorax. Six
      patients had primary lung cancer, two had metastases, and one each had
      neurofibroma, pericardial cyst, chondroma of the rib, and malignant mesothelioma.
      All 12 tumors abutted the chest wall or mediastinum and could not be separated by
      conventional CT. Between 400 and 800 ml of air was injected into the pleural
      space before a second CT scan was obtained. No invasion was found at surgery in
      cancers that were separated from chest wall or mediastinum on CT scans. Surgery
      revealed chest wall invasion in three patients in whom the CT scans showed that
      the tumor was not separated from the chest wall. Only one patient with a tumor
      that was not separated from the mediastinum on CT did not have mediastinal
      invasion: in this case, only adhesions were found at surgery. Thus, in the eight
      patients with primary lung cancer and metastasis, sensitivity, specificity, and
      accuracy were 100%, 80%, and 88%, respectively. In four patients with mediastinal
      or pleural tumor, CT combined with pneumothorax was useful for establishing the
      origin of tumors. In all, 11 of the 12 patients were correctly evaluated by using
      this method. No complications occurred, except for mild chest discomfort in one
      patient. This study suggests that chest CT combined with artificial pneumothorax
      is useful for the evaluation of the extension of lung cancer into the chest wall
      and mediastinum and for the diagnosis of the site of origin of intrathoracic
      tumors.

PMID- 2003430
TI  - Lymphoma of the lung: CT findings in 31 patients.
AB  - Lymphomatous involvement of the lungs is often a difficult clinical and
      radiologic diagnosis to make, yet is often critical in determining treatment. To
      better define the CT appearance of pulmonary lymphoma, we undertook a
      retrospective review of 31 patients with recurrent or secondary non-Hodgkin
      lymphoma or Hodgkin disease and lung parenchymal involvement on CT scans.
      Diagnoses were confirmed either by lung biopsy or by disease regression or
      progression with appropriate therapy. The CT scans were evaluated for the
      following findings: (1) nodules less than 1 cm, (2) a mass or masslike
      consolidation greater than 1 cm with or without cavitations or bronchograms, (3)
      alveolar or interstitial infiltrates, (4) masses of pleural origin, (5)
      peribronchial or perivascular thickening with or without atelectasis, (6) pleural
      effusions, and (7) hilar or mediastinal lymphadenopathy. The most common CT
      finding was a mass or masslike consolidation larger than 1 cm, seen in 21 (68%)
      of the 31 patients. The second most common finding was nodules less than 1 cm (19
      patients). Sixty-eight percent of patients had three or more of the CT
      abnormalities. Lymphoma involving the lung parenchyma causes a variety of CT
      findings, the most common being a mass or masslike consolidation. Two-thirds of
      patients have more than one type of CT finding simultaneously.

PMID- 2003431
TI  - Mediastinal seroma after esophagogastrectomy.

PMID- 2003432
TI  - Noncompaction of ventricular myocardium: CT appearance.

PMID- 2003433
TI  - Medicolegal aspects of breast imaging: variable standards of care relating to
      different types of practice.

PMID- 2003434
TI  - Adrenal myelolipoma.

PMID- 2003435
TI  - Detection of active intraabdominal arterial hemorrhage: value of dynamic contrast
      enhanced CT.
AB  - Contrast-enhanced dynamic CT was used prospectively to diagnose and locate the
      site of active arterial intraabdominal hemorrhage in 18 patients. Active arterial
      extravasation was confirmed by angiography in five patients and by immediate
      surgery in nine. Two patients not undergoing surgery or angiography required
      multiple blood transfusions to correct rapidly falling hematocrit due to a
      coagulopathy. One patient died of hypovolemic shock, and autopsy confirmed a
      large acute retroperitoneal hematoma. Another patient with a splenic laceration
      and massive hemoperitoneum on CT had no active bleeding at the time of surgery,
      which was delayed 1 hr from the time of the CT. All patients were clinically
      thought to be hemodynamically stable and had systolic blood pressures greater
      than 110 mm Hg at the time of CT. In seven patients, hypotension developed either
      during (two patients) or immediately after (five patients) CT scanning,
      necessitating either immediate surgery or angiographic embolization. Contrast
      enhanced dynamic CT is valuable in the diagnosis and localization of active
      arterial intraabdominal hemorrhage. Identification of the anatomic site of this
      potentially life-threatening hemorrhage is critical in determining whether
      immediate laparotomy or angiographic embolization is the preferred method of
      treatment.

PMID- 2003436
TI  - Diagnosis of pneumoperitoneum on supine abdominal radiographs.
AB  - A blinded, retrospective study was performed to determine the value of supine
      abdominal radiographs in diagnosing pneumoperitoneum. Supine films from 44 cases
      of pneumoperitoneum were randomly interspersed among supine films from 87 control
      subjects without free air, and the films were reviewed for the presence or
      absence of various signs of pneumoperitoneum, including Rigler's sign (gas on
      both sides of the bowel wall), the falciform ligament sign (gas outlining the
      falciform ligament), the football sign (gas outlining the peritoneal cavity), the
      inverted-V sign (gas outlining the medial umbilical folds), and the right-upper
      quadrant gas sign (localized gas in the right upper quadrant). One or more of
      these signs were present in 26 cases (59%) of pneumoperitoneum, including the
      right-upper-quadrant gas sign in 18 cases (41%), Rigler's sign in 14 cases (32%),
      and the falciform ligament and football signs in one case each (2%).
      Unfortunately, there were frequent errors in the interpretation of the right
      upper-quadrant gas sign and Rigler's sign, with a total of 11 false-positive
      cases (13%). Further analysis of the true-positive right-upper-quadrant gas signs
      showed that these gas collections were always triangular or linear with an
      inferolateral to superomedial orientation and, if triangular, a concave
      superolateral border. In the true-positive Rigler's signs, the bowel wall
      thickness ranged from 1 to 8 mm, whereas the false positives all had a bowel wall
      thickness of 1 mm or less. Proper interpretation of the various signs of
      pneumoperitoneum on supine films should lead to more accurate diagnosis of this
      condition.

PMID- 2003437
TI  - Imaging the gallbladder: a historical perspective.
AB  - After Wilhelm Conrad Roentgen's discovery of the X-ray in 1895, it was initially
      thought that gallstones could not be visualized. Surgeons relied solely on the
      clinical examination to detect biliary disease. Today, no evaluation of the
      gallbladder would be complete without the performance of an imaging study.
      Radiology has gone through several eras in the imaging of gallstones. The plain
      film era, 1895-1924, was characterized by techniques that improved soft-tissue
      detail, allowing better detection of radiopaque stones. The contrast media era,
      1924-1960, was initiated by the invention of IV cholecystography. In 1925, oral
      cholecystography was developed. During the era of expanding technology, 1960
      1979, percutaneous transhepatic cholangiography, scintigraphy, and sonography
      came into use. The therapeutic era began in the 1980s.

PMID- 2003438
TI  - Amyloidosis of the small intestine: findings on double-contrast radiographs.
AB  - The appearance of the small intestinal mucosa on double-contrast barium
      examinations was studied in 26 patients with proved intestinal amyloidosis.
      Findings included innumerable fine granular densities 1-3 mm in diameter (16
      patients), multiple nodular densities 3-4 mm in diameter (four patients),
      multiple polypoid protrusions 4-10 mm in diameter (three patients),
      irregularities of Kerckring folds (12 patients), and multiple erosions (eight
      patients). The multiple nodular densities and erosions disappeared after the
      patients were treated with total parenteral nutrition. The other abnormalities
      remained unchanged on follow-up examinations. Our results indicate that double
      contrast radiographic findings of the small intestine in patients with
      amyloidosis include mucosal abnormalities that vary according to the pathologic
      type of amyloid deposition.

PMID- 2003439
TI  - Pancreatic microcystic adenoma presenting with acute hemoperitoneum: CT
      diagnosis.

PMID- 2003440
TI  - Hydatid cyst of the liver: identification of detached cyst lining on CT scans
      obtained after cyst puncture.

PMID- 2003441
TI  - Carcinoma of the cervix: value of MR imaging in detecting parametrial
      involvement.
AB  - In patients with cervical carcinoma, precise knowledge of parametrial tumor
      extension affects the therapeutic decision between surgery and radiation therapy.
      The purpose of this prospective study was to determine the efficacy of MR imaging
      in detecting the presence or absence of parametrial invasion in patients with
      cervical cancer thought clinically to be confined to the cervix. Twenty-five
      consecutive patients were included in the study. All patients underwent radical
      hysterectomy or total abdominal hysterectomy and had detailed histologic
      evaluation of the parametrium. Ten had pathologic evidence of parametrial
      invasion; in the remaining 15, no parametrial invasion was identified
      pathologically. MR findings were compared with pathologic findings in all cases.
      For determining parametrial involvement, MR imaging had an accuracy of 88%, a
      sensitivity of 100%, and a specificity of 80%. Our results suggest that MR
      imaging is a reliable means of assessing parametrial invasion by cervical cancer.

PMID- 2003442
TI  - A simplified method for antegrade ureteral stent placement.

PMID- 2003443
TI  - Acute effects of exercise on MR imaging of skeletal muscle: concentric vs
      eccentric actions.
AB  - Eccentric (lengthening) muscle actions involve the forced lengthening of active
      muscles. Compared with concentric (shortening) muscle actions subjected to the
      same relative work load, eccentric actions have lower oxygen consumption
      requirements, fewer activated motor units, and less lactate production. This
      study was conducted to determine if T2-weighted MR could show any difference in
      muscles performing these specific types of actions and, therefore, be useful for
      physiologic investigations of eccentric and concentric actions. Five subjects
      performed exhaustive exercise by doing isolated concentric actions (raising a
      dumbbell, flexing at the elbow) and eccentric muscle actions (lowering a
      dumbbell, extending the contralateral arm). T2-weighted MR images of the arms
      were obtained immediately before and after exercise. Muscles that performed
      concentric actions had increases in signal intensity, whereas muscles that
      performed eccentric actions showed little or no change. T2 relaxation times
      increased significantly (p less than .01) in all volunteers, but T2 relaxation
      times for the muscles that performed concentric actions were significantly higher
      than those for muscles that performed eccentric actions (p less than .01).
      Therefore, T2 times increased with both concentric and eccentric actions, but the
      images failed to show the changes in the muscles that performed the eccentric
      actions. These data demonstrate that assessment of T2 values can be used to
      distinguish between muscles that perform concentric actions and those that
      perform eccentric actions, and this phenomenon may be useful for further
      physiologic investigations of these specific types of muscle actions.

PMID- 2003444
TI  - Repair of Achilles tendon ruptures with a polylactic acid implant: assessment
      with MR imaging.
AB  - An investigational tendon repair device composed of a polymer of lactic acid
      (PLA) is currently undergoing multicenter clinical trials for use in repairing
      rupture of the Achilles tendon. The advantages of the PLA device include high
      tensile strength and the induction of a rapid proliferative tissue response
      resulting in a shorter rehabilitation period than with conventional surgical
      repair. We reviewed 16 MR examinations performed in 10 patients 3-35 months after
      repair to characterize the MR appearance. All 16 T1-weighted sagittal images
      revealed a thickened fusiform tendon with streaks of moderate signal within the
      tendon corresponding to the PLA device and its surrounding collagenogenic
      response. The double-echo T2-weighted axial images at the mid tendon level
      demonstrated progressive changes in the signal pattern of the central portion of
      the tendon that reflected the maturation of the healing tendon. All tendons
      repaired with PLA implants were uniformly hypertrophied relative to the
      contralateral normal side because of the induced proliferative collagenogenic
      ingrowth. Two follow-up MR examinations were performed in six patients and showed
      mean reductions in tendon caliber of 24% and 30% at the mid and inferior levels.
      MR imaging of the Achilles tendon repaired with PLA implants shows a diffusely
      thickened tendon with streaks of signal within the tendon that distinguish it
      from tendons repaired by conventional techniques.

PMID- 2003445
TI  - Extension of growth-plate cartilage into the metaphysis: a sign of healing
      fracture in abused infants.
AB  - The present study was carried out to determine if healing metaphyseal injury in
      abused infants is accompanied by an increase in the thickness of the growth-plate
      zone of hypertrophic cartilage and if a radiolucent extension from the growth
      plate into the metaphysis correlates with this histologic indicator of healing
      fracture. The radiologic studies of 13 infants who died with evidence of
      inflicted injury were reviewed. Thirteen distal metaphyseal fractures were
      identified. Histologically, nine of these fractures were noted to be healing and
      four showed no evidence of healing. The nine healing injuries were accompanied by
      statistically significant thickening of the zone of hypertrophic cartilage. Seven
      of these demonstrated localized areas of hypertrophic cartilage extension; in six
      of these, corresponding radiolucent extensions of the growth plate into the
      metaphysis were seen. The extensions tended to be single and focal with minimal
      osseous injury and broad and multiple with extensive injury. No similar extension
      was visible in the four acute injuries. Because metaphyseal injuries are
      notoriously difficult to date, the presence of a reliable radiologic indicator of
      healing metaphyseal fracture can be important in the evaluation of infant abuse.
      Because the radiologic findings reflect the histologic alterations, extension of
      the growth-plate cartilage into the metaphysis may have implications for
      estimating fracture age.

PMID- 2003446
TI  - Normal metaphyseal radiologic variants not to be confused with findings of infant
      abuse.
AB  - Postmortem high-detail skeletal radiography of 78 infants who died of the sudden
      infant death syndrome was performed during a 3-year period. Review of the studies
      reveals a variety of distinct radiologic variants that should not be confused
      with the metaphyseal injuries caused by infant abuse.

PMID- 2003447
TI  - Osteomyelitis of the talus: an unusual cause of limping in childhood.
AB  - Hematogenous osteomyelitis of the talus is a rare and infrequently considered
      cause of limping in children. We describe five children younger than 2 years of
      age with osteomyelitis of the talus who had a limp and a paucity of
      constitutional symptoms. Conventional radiography and scintigraphy were the
      imaging techniques used. The usual radiologic features include soft-tissue
      swelling and an osteolytic defect in the talus without sequestrum formation of
      periosteal reaction. Bone scans were positive in all cases and led to the
      localization of the lesion in two patients. Definitive diagnosis was made in all
      cases only after needle aspiration or open biopsy and curettage. Increased
      awareness of this unusual lesion and its subtle early radiologic manifestations
      will allow prompt diagnosis and treatment.

PMID- 2003448
TI  - Polysplenia syndrome with congenital short pancreas.

PMID- 2003449
TI  - Inferior vena caval filters: analysis of five currently available devices.

PMID- 2003450
TI  - Atypical contrast reactions associated with systemic interleukin-2 therapy.

PMID- 2003451
TI  - An ultrafast network for communication of radiologic images.
AB  - The three most difficult problems in making picture archiving and communication
      systems (PACS) a clinical reality in radiology are image archiving, very high
      resolution display stations, and high-speed networking. This article considers
      high-speed image transmission through a high-capacity network. Our laboratory has
      tested several commercially available high-speed networks over the past year.
      Only one of these networks (UltraNet) has adequate throughput and capacity
      potential necessary for our PACS. The focus of this experiment is to determine
      the throughput and capacity characteristics of this star topology networking
      scheme as they relate to the operation of a PACS in the clinical environment. A
      large-scale test was done to gauge network performance for three networking
      configurations modeling those in a PACS: duplex, parallel, and relay. Ten
      computers used in our PACS (Sun 3 and 4 computers) were connected with UltraNet.
      For point-to-point throughput (half-duplex model), the network delivers up to 3.1
      megabytes/sec for Sun 3 computers and 6.8 megabytes/sec for the Sun Sparcserver
      490. As regards capacity considerations (parallel model), five parallel image
      transfer processes generated a maximum of 13.9 megabytes/sec through the network.
      Only a slight degradation in individual process throughput was observed (1.4%).
      With regard to shared access to high-contention resources on the PACS network
      (e.g., archive servers), this network demonstrated equal sharing of server
      networking capacity between the various client computers. With the encouraging
      results of this experiment, we believe that the UltraNet network will be
      sufficient for the image communication requirements of our PACS. We are
      proceeding with the implementation of UltraNet as the high-speed backbone of our
      extended PACS network.

PMID- 2003452
TI  - Radiology Summit Meeting--1990: action strategies for the new decade.

PMID- 2003453
TI  - Recommended textbooks for radiology residents.

PMID- 2003454
TI  - Modification of standard arterial puncture technique to reduce risk of accidental
      contact with blood.

PMID- 2003455
TI  - The surgical glove and endorectal sonography.

PMID- 2003456
TI  - Guidelines for use of nonionic contrast media.

PMID- 2003457
TI  - Localization of transected wire.

PMID- 2003458
TI  - Volvulus of a pedunculated hemangioma of the liver.

PMID- 2003459
TI  - Recall of E-Z-EM balloon-retaining barium enema tips.

PMID- 2003460
TI  - CT findings of a rectal intussusception.

PMID- 2003461
TI  - CT findings in anorectal tuberculosis.

PMID- 2003462
TI  - Intratumoral fat in a renal cell carcinoma.

PMID- 2003463
TI  - Pregnancy complicated by ovarian torsion.

PMID- 2003464
TI  - Doppler nomenclature, a new frontier.

PMID- 2003465
TI  - High-velocity jets from 5-French catheters.

PMID- 2003466
TI  - Isolated thrombosis of left-sided vena cava.

PMID- 2003468
TI  - More on the P value.

PMID- 2003467
TI  - Making memories at Matsumoto.

PMID- 2003469
TI  - P values.

PMID- 2003470
TI  - Clavicular fractures in neonates: frequency vs significance.

PMID- 2003471
TI  - Clavicular fractures in neonates.

PMID- 2003473
TI  - Your child's best friend: TV or not TV.

PMID- 2003472
TI  - What about gay teenagers?

PMID- 2003474
TI  - Psychosocial predictors of maternal and infant health among adolescent mothers.
AB  - Past work suggests that stressful life events and social support are
      significantly associated with a broad range of child health outcomes. Such
      associations have remained, however, generally modest in magnitude, suggesting
      that stress and support may be only proxy measures for a deeper, more central
      aspect of childhood psychosocial experience. One aspect of young people's lives
      that could plausibly mediate the effects of stress and social support on health
      is the sense of stability and "permanence" in ongoing life experience. We
      developed a standardized psychometric instrument for measuring a "sense of
      permanence" and employed the measure in a prospective 1-year study of health
      outcomes among 89 adolescent mothers and their infants. Psychosocial and
      demographic factors were significantly predictive of maternal, but not infant,
      health outcomes, and the sense of permanence appeared to operate as a "final
      common pathway" in the influence of psychosocial variables on health and illness
      end points. Results of the study underscore the importance of continuity and
      stability in childhood and suggest that changes in an individual's sense of
      permanence may underlie the previously documented health effects of stressful
      life events and social support.

PMID- 2003475
TI  - Photographing the physically abused child. Principles and practice.
AB  - Photographic documentation of significant findings is an important part of any
      child abuse evaluation. High-quality photographs of significant physical findings
      may be important in helping courts to adjudicate whether child abuse has taken
      place. The physician evaluating abused children should ensure adequate
      photographic documentation of visible lesions. Physicians who care for abused
      children should be familiar with the basic principles and techniques of clinical
      photography. These include good equipment, adequate lighting, and planned
      composition. Equally important is a working knowledge of camera equipment, film
      procedure, and medicolegal implications. This review outlines for the practicing
      physician the basic concepts and techniques of photographing abused children.

PMID- 2003476
TI  - Ventriculitis in newborns with myelomeningocele.
AB  - It has frequently been cited that a delay in back closure of beyond age 48 hours
      in newborns with myelomeningocele is associated with an increased risk of
      ventriculitis. It has been suggested that antibiotic therapy prior to surgery
      might minimize this risk. We reviewed our experience with ventriculitis in
      newborns with myelomeningocele and its relationship to antibiotic usage and time
      of back closure. Of 186 newborns, ventriculitis developed in 13 (7%), and there
      was no observed difference by time of back closure, clinical severity of infant
      at birth, status of myelomeningocele sac at birth, or type of delivery. There was
      a significant association between antibiotic usage and ventriculitis among the
      infants with delayed surgery, of which only one (1%) of 73 receiving broad
      spectrum antibiotic prophylactic therapy developed ventriculitis compared with
      five (19%) of the 27 who did not receive antibiotics. Our data support the
      suggestion that antibiotic treatment is effective in minimizing the risk of
      ventriculitis among infants with myelomeningocele undergoing surgery after 48
      hours of age.

PMID- 2003477
TI  - Stimulant medication and attention deficit-hyperactivity disorder. The child's
      perspective.
AB  - Fifty-eight children receiving stimulant medication for attention deficit
      hyperactivity disorder at referral clinics for learning disabilities at two
      teaching hospitals in Massachusetts were invited to participate in a study of
      their knowledge and attitudes. The 45 respondents and parents completed separate
      questionnaires concerning how they felt about receiving stimulant medication.
      Eighty-nine percent of the children felt that the medication was helpful and 78%
      liked or were indifferent to it despite a high rate (85%) of reported side
      effects. The five children (11%) who responded that they would stop taking
      stimulant medication if they could were more likely to perceive the medication as
      unhelpful and were receiving standard methylphenidate hydrochloride rather than a
      long-acting preparation. We conclude that children's perspectives on medication
      should be elicited directly and sustained-release medication may be more
      acceptable to children with attention deficit-hyperactivity disorder.

PMID- 2003478
TI  - Capillary refilling (skin turgor) in the assessment of dehydration.
AB  - This study was undertaken to evaluate the usefulness of skin turgor or capillary
      refilling in estimating the degree of dehydration in infants with diarrhea. After
      initial standardization of the technique, capillary filling time was found to be
      more reproducible when measured in the fingernail bed after applying just the
      amount of pressure necessary to blanch the nail bed. Capillary refilling time in
      30 normal infants 2 to 24 months of age was 0.81 +/- 0.31 seconds. Capillary
      filling time was then measured in 32 infants with diarrhea admitted to the
      hospital and correlated to the degree of dehydration as estimated from the
      difference in weight from the time of hospital admission to the weight after
      rehydration. A turgor time of 1.5 seconds or less was found to be indicative of a
      less than 50-mL/kg deficit or of a normal infant; 1.5 to 3.0 seconds suggests a
      deficit between 50 and 100 mL/kg, and more than 3 seconds suggests a deficit of
      more than 100 mL/kg.

PMID- 2003479
TI  - Practice management training for pediatric residents.
AB  - In 1986, a practice management training program was developed for pediatric house
      staff. In conjunction with this program, pediatric residents for the following 2
      years completed questionnaires regarding their career goals, interests, and
      perceived competence in practice management. Postgraduate level-3 residents who
      completed the program felt more competent than postgraduate level-1 residents in
      all areas of practice management and were more likely to take an active role in
      managing their practice. There was a significant difference between postgraduate
      level-1 and level-3 residents who completed the program in several areas:
      feelings of overall competence in office management, choosing a practice
      location, office staff, appointment system, billing system, office computer, fee
      schedules, telephone management, and setting up an office laboratory. Exposure to
      a practice management program during residency training may better prepare future
      pediatricians for a successful practice.

PMID- 2003480
TI  - Breast-feeding initiation in a triethnic population.
AB  - The influence of sociodemographic factors on the initiation of breast-feeding was
      evaluated in a triethnic population from Galveston, Tex. Breast-feeding rates
      were 44.3% among Anglo-Americans, 13.5% among blacks, and 26.6% among Mexican
      Americans. Mexican ethnicity, education levels among Anglo-Americans, and marital
      status were associated with the initiation of breast-feeding. Odds ratios for
      breast-feeding were 1.94 (95% confidence interval, 1.10 to 3.43) times higher in
      Mexican-American compared with black women, and 1.94 (95% confidence interval,
      1.34 to 2.83) times higher in married than unmarried women. Anglo-American
      ethnicity and education, as main effects, were not significantly associated with
      breast-feeding, but their interaction was. Among Anglo-American women (in
      comparison with black women), the odds ratios of breast-feeding increased with
      education level, ranging from 1.84 for those with less than an eighth grade
      education to 7.46 for those with some college. In contrast to recent findings
      suggesting that education was more important than ethnicity in predicting breast
      feeding, the odds of breast-feeding among Anglo-American compared with black
      women depended on the level of maternal education, but the odds of breast-feeding
      for Mexican-American vs black women did not depend on education.

PMID- 2003481
TI  - Esophageal motility in children with Hirschsprung's disease.
AB  - Esophageal motility was studied in 12 children with Hirschsprung's disease to see
      if extracolonic motor dysfunction was present in this disorder. Manometric
      tracings were compared with those from eight children with idiopathic megacolon
      and from 10 children without esophageal disease or constipation. Amplitude of
      esophageal contraction waves was significantly higher in children with
      Hirschsprung's disease than in the other two groups. Swallows that were followed
      by simultaneous contractions or double-peaked waves were also more common in the
      group with Hirschsprung's disease (subjects with Hirschsprung's disease, subjects
      with megacolon, and controls; 57%, 10%, and 8%, respectively). Lower esophageal
      sphincter characteristics did not differ among the three groups. The increase in
      simultaneous contractions and double-peaked waves persisted in those children who
      were reexamined following surgery for Hirschsprung's disease, whereas wave
      amplitudes fell to a level similar to that observed in the other groups. These
      data suggest that gastrointestinal motor dysfunction in persons with
      Hirschsprung's disease is not restricted to the colon, and that some of the
      observed abnormalities in esophageal motility do not reflect nonspecific
      responses to megacolon or colonic obstruction.

PMID- 2003482
TI  - Cortical resection for children with epilepsy. Perspectives in pediatrics.

PMID- 2003483
TI  - Adipsic hypernatremia in two sisters.
AB  - We describe two sisters with chronic hypernatremia, lack of thirst, and
      inappropriate osmoregulated vasopressin secretion. Only one sister, who presented
      with microcephaly and developmental delay, showed signs of dysplasia of the
      midline structures (ie, septum pellucidum and corpus callosum) and a large
      intracranial cyst. Neither sister showed any signs of thirst, even when
      osmolality exceeded 337 mmol/kg. In both patients, the vasopressin secretion did
      not respond to either osmotic or nonosmotic stimuli or was suppressed by a water
      load. Plasma osmolality values returned to normal after treatment with forced
      hydration and a vasopressin analogue, desamino-D-arginine vasopressin. These
      findings indicate a severe defect in the hypothalamic osmoreceptors that control
      thirst and vasopressin secretion. To our knowledge, this is the first report of
      such a disorder in two sisters.

PMID- 2003484
TI  - Anergy in pediatric head trauma patients.
AB  - To assess cellular immune function in children following severe blunt trauma, 25
      children (mean: age, 7.1 years; Injury Severity Score, 34.9; and Glascow Coma
      Score, 5.6) admitted with severe trauma were examined with the use of the CMI
      Multitest system (Merieux Institute, Miami, Fla) to test delayed-type
      hypersensitivity. Patients were monitored for evidence of infection for the next
      3 weeks. Ten children (mean: age, 6.2 years; Injury Severity Score, 31.2; and
      Glascow Coma Score, 5.4) admitted with severe trauma had the percentage of
      circulating lymphocyte subpopulations (pan-T cell marker T101, CD4, CD8, and B
      cells) measured on day 1 and then weekly for 3 weeks. Fourteen (56%) of the 25
      children had no reaction to any of the skin tests (anergic). Eleven (79%) of 14
      anergic patients became infected, while three (27%) of 11 of the nonanergic
      children became infected. There were no significant changes in pan-T cell marker
      T101, CD4, or CD8 lymphocyte populations in the 3 weeks following injury;
      however, absolute numbers of circulating B cells dropped significantly by day 7.
      These data indicate that children with severe trauma who are anergic are
      significantly more susceptible to infection. Unlike the results reported
      previously in adult trauma patients, these children had no significant
      fluctuations in T-cell populations; however, there was a significant decrease in
      circulating B cells in the first week. The use of the delayed-type
      hypersensitivity skin test can aid in identifying which patients are at an
      increased risk for nosocomial infection.

PMID- 2003485
TI  - Endocrine function in children with human immunodeficiency virus infection.
AB  - We sought to determine if failure to thrive in pediatric patients with the human
      immunodeficiency virus could be explained based on endocrine dysfunction.
      Fourteen human immunodeficiency virus-infected pediatric patients, all of whom
      had adequate nutritional status, underwent endocrine evaluation. Growth hormone
      and cortisol responses to glucagon stimulation were adequate. Despite this, eight
      of the 12 subjects had low somatomedin C levels. Although all patients were
      clinically and biochemically euthyroid, 36% (5/14) demonstrated elevated baseline
      and peak thyrotropin levels in response to thyroid releasing hormone, suggesting
      a state of compensated hypothyroidism. Although the importance of these findings
      is unclear, it is possible that subtle alterations of thyroid regulation may
      contribute to failure to thrive in some pediatric patients infected with human
      immunodeficiency virus and may represent a potentially correctable defect.

PMID- 2003486
TI  - Radiological case of the month. A pediatric case of Eagle's syndrome.

PMID- 2003487
TI  - Picture of the month. Acropustulosis of infancy.

PMID- 2003489
TI  - Colorado Society explores biotechnology, AIDS at annual meeting.

PMID- 2003488
TI  - Quality of care for hospitalized Medicare patients improves despite prospective
      pricing system.

PMID- 2003490
TI  - New ruling unfair to nuclear pharmacists.

PMID- 2003491
TI  - Notifying patients of adverse drug reactions.

PMID- 2003492
TI  - Extended-release niacin not problem free.

PMID- 2003493
TI  - Clinical pharmacy for all.

PMID- 2003494
TI  - Benefits of training pharm.D. students.

PMID- 2003495
TI  - A model for ambulatory-care pharmaceutical services.

PMID- 2003496
TI  - Pharmacist salaries and hiring practices in teaching hospitals.
AB  - A survey of selected teaching hospitals was conducted in early 1990 to determine
      salary ranges for pharmacist positions, salaries at which pharmacists were
      typically hired for these positions, differences in salary between clinical
      practitioner and managerial positions, and geographic differences in these
      salaries. Surveys were mailed to 50 members of the University Hospital Consortium
      (UHC) and 50 other university-affiliated and non-university-affiliated hospitals
      believed to be comparable to the investigators' hospital. Hospital capacity and
      census data, numbers of pharmacist and support staff positions, qualifications
      preferred and required for those positions, and salary information were
      requested. Data from 22 UHC hospitals and 23 non-UHC hospitals were evaluated.
      Relative to average daily census, UHC hospitals indicated higher pharmacist
      staffing levels and non-UHC hospitals reported higher support staff levels. More
      non-UHC hospitals than UHC hospitals (69.2% versus 43.5%) used an integrated
      model for delivery of clinical and distributive services. Nationally, the
      reported annual salaries were as follows: staff pharmacist, $34,881 to $47,906;
      clinical pharmacist, $37,768 to $51,564; clinical specialist, $38,905 to $55,282;
      supervisor, $39,905 to $54,416; assistant director, $43,554 to $58,758. Overall,
      typical hire rates (THRs) exceeded mean minimum salaries by about 10%. The
      percentages by which THRs exceeded mean minimum salaries were greatest in the
      West for staff pharmacist, clinical pharmacist, and clinical specialist positions
      and greatest in the Midwest for supervisor and assistant director positions. THRs
      for supervisors and assistant directors exceeded those for clinical specialists.
      Respondents' preferences varied regarding advanced education and training, and
      their actual requirements did not match their stated preferences.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 2003497
TI  - Influenza vaccination program for elderly outpatients.
AB  - The effect of pharmacist interventions on the rate at which elderly outpatients
      were offered influenza vaccination was studied. Pharmacists at a university-based
      ambulatory-care facility reviewed the medical records of a random sample of
      control patients over the age of 65 who had been seen during the influenza
      vaccination months in 1987 or 1988 or both years. The purpose was to estimate the
      percentage of patients who had been documented as being offered influenza
      vaccination. In 1989 an intervention program was undertaken consisting of
      inservice presentations to the facility's nursing staff, dissemination of
      influenza information sheets to patients upon check-in, placement of wall
      posters, placement of reminders in patient charts, and institution and
      advertisement of a vaccination clinic. At the end of the 1989 vaccination season,
      the records of a random sample of intervention group patients were reviewed to
      determine the proportion of patients who had been offered influenza virus
      vaccine. Of the 280 control group patients, 47% were offered influenza
      vaccination during 1987 and 1988. A significantly higher proportion of the 153
      intervention group patients, 71%, was offered influenza vaccine during 1989. A
      combination of pharmacist-initiated interventions significantly increased the
      number of elderly patients who were offered vaccinations during scheduled clinic
      visits.

PMID- 2003498
TI  - Pharmacy-controlled documentation of drug allergies.
AB  - The implementation of a pharmacy-enforced policy for documenting drug allergies
      is described. After two incidents at a 600-bed teaching hospital in which
      patients experienced severe allergic reactions to drugs, an audit was conducted
      to evaluate the existing drug allergy documentation policy. Physicians documented
      allergies in medical charts and treatment orders for 68% and 78% of patients,
      respectively; no initial drug orders contained this information. Nurses
      documented allergies in admission assessments, medication records, and charts for
      71%, 61%, and 15% of patients, respectively. Only 2% of pharmacy computerized
      drug profiles contained allergy information. A new policy for drug allergy
      documentation was instituted. Physicians provide allergy information on the first
      written drug order. Nurses independently solicit allergy information and check it
      against that provided by the physician. Pharmacists enter the information into
      the patient's drug profile. If the information has not been obtained, the drug is
      not dispensed. Repeat audits two months and one year after the policy was put in
      place showed significant improvements in the completeness and accuracy of drug
      allergy documentation by pharmacists and physicians. In general, documentation by
      nurses did not improve to the degree found for pharmacists and physicians. A
      policy that gave pharmacists the primary responsibility for ensuring that drug
      allergy information was obtained before drugs were dispensed was effective in
      improving allergy documentation by physicians and pharmacists.

PMID- 2003499
TI  - Impact of medication profile review on prescribing in a general medicine clinic.
AB  - The effect of medication profile review by a clinical pharmacist on prescribing
      in a general medicine clinic was studied. Patients who were receiving five or
      more prescription or nonprescription medications were randomly assigned to an
      intervention group (n = 315) or a control group (n = 257). A clinical pharmacist
      reviewed the medication profile of each intervention group patient on the day
      before the patient's clinic visit and attached a written profile review to the
      medical record for study by the physician during the visit. After each clinic
      day, the pharmacist obtained updated records of patients in both groups and
      collected data on the number and cost of medications ordered before and after the
      visits. After the clinic visits, the average number of medications and the
      average monthly medication cost per patient decreased by 0.21 and $0.60,
      respectively, for the intervention group, compared with increases of 0.48 and
      $3.31 for the control group. The net result of a single profile review was a
      decrease of 0.69 prescription per patient, for a monthly medication cost savings
      of $3.91. The number and cost of medications that were discontinued were
      significantly higher in the intervention group. The intervention group also had
      significantly fewer drugs added for previously documented medical problems.
      Medication profile review by a clinical pharmacist reduced both the number and
      cost of drugs for patients receiving five or more medications.

PMID- 2003500
TI  - Stability of zidovudine in 5% dextrose injection and 0.9% sodium chloride
      injection.
AB  - The stability of zidovudine at a concentration of 4 mg/mL in 5% dextrose
      injection and 0.9% sodium chloride injection in polyvinyl chloride infusion bags
      stored at room and refrigerated temperatures for up to eight days was studied.
      Zidovudine was diluted in 5% dextrose injection and in 0.9% sodium chloride
      injection to a concentration of 4 mg/mL. Six admixtures were prepared with each
      diluent; three were stored at room temperature (25 +/- 1 degree C) and three were
      refrigerated (4 +/- 1 degree C). At 0, 3, 6, 24, 48, 72, and 192 hours, 2-mL
      aliquots were removed. One milliliter of each aliquot was diluted to a zidovudine
      concentration of approximately 40 micrograms/mL and assayed in duplicate by a
      stability-indicating high-performance liquid chromatographic method. Visual
      inspection was performed at each sampling time for precipitation, turbidity,
      color change, and gas formation. Sample pH was recorded at 0 and 192 hours. In
      all admixtures, more than 97% of the initial zidovudine concentration remained
      throughout the study period. No visual or pH changes were observed. Zidovudine 4
      mg/mL in admixtures with 5% dextrose injection or 0.9% sodium chloride injection
      stored in polyvinyl chloride infusion bags was stable for up to 192 hours (eight
      days) at room temperature and under refrigeration.

PMID- 2003501
TI  - Stability of amphotericin B in 5% dextrose injection at concentrations used for
      administration through a central venous line.
AB  - The stability of amphotericin B in 5% dextrose injection was studied at
      concentrations used for administration through a central venous line.
      Amphotericin B 60, 80, and 100 mg was diluted in 50 mL of 5% dextrose injection;
      final mean +/- S.D. concentrations after adjustment for total volume were 0.92 +/
      0.01, 1.20 +/- 0.03, and 1.40 +/- 0.03 mg/mL, respectively. For each
      concentration, six admixtures were prepared; of these, three were stored at 25
      degrees C and three at 6 degrees C. Amphotericin B concentration was tested at 0,
      4, 12, 24, and 36 hours by stability-indicating high-performance liquid
      chromatography. The admixtures were inspected visually at each time point for
      precipitation, turbidity, gas formation, and color change, and the pH was
      measured. Concentrations of amphotericin B remained within 3% of initial
      concentrations at each time point at both storage temperatures. No precipitation,
      turbidity, gas formation, or color change was observed, and no changes in pH were
      measured. Amphotericin B in 5% dextrose injection was stable at concentrations of
      0.92, 1.20, and 1.40 mg/mL when stored at 6 and 25 degrees C for up to 36 hours.

PMID- 2003502
TI  - Stability of miconazole in peritoneal dialysis fluid.
AB  - The stability of miconazole when mixed with peritoneal dialysis (PD) fluid and
      stored in plastic bags or glass ampuls was determined. Admixtures of miconazole
      and PD fluid were prepared in 2-L polyvinyl chloride (PVC) bags and in 1-mL glass
      ampuls to give a nominal initial concentration of 20 mg/mL. Duplicate samples of
      each solution were assayed in duplicate by high-performance liquid chromatography
      immediately after preparation and at various intervals up to nine days. All
      admixtures were stored in ambient light at 20 +/- 2 degrees C. A substantial loss
      of miconazole (greater than 10% of the initial concentration) occurred within
      four hours for admixtures stored in PVC bags, whereas similar solutions retained
      more than 90% of their initial miconazole concentration for at least three days
      when stored in glass ampuls under the same conditions. This suggests that the
      observed loss of miconazole from the PVC bags was largely due to an interaction
      with the container, rather than to chemical degradation in solution. About 28% of
      the miconazole lost from the solution during storage in PVC bags was recovered
      from the plastic by methanolic extraction. The rapid loss of miconazole when the
      drug was mixed with PD fluid and stored in PVC bags indicates that such
      admixtures should be prepared immediately before administration.

PMID- 2003503
TI  - Stability of cefazolin sodium in peritoneal dialysis solutions.
AB  - The stability of cefazolin sodium was studied in two commonly used peritoneal
      dialysis solutions. Cefazolin (as the sodium salt) 250 mg was added to 500-mL
      bags of dialysis solution containing 1.5% or 4.25% dextrose injection to yield a
      target concentration of 0.5 mg/mL. Of 18 bags containing 1.5% dextrose injection,
      six were stored at 4 degrees C, six at 25 degrees C, and six at 37 degrees C.
      Similarly, of 18 bags containing 4.25% dextrose injection, groups of six were
      stored at each temperature. Samples were measured for cefazolin concentration by
      high-performance liquid chromatography at 0, 3, 7, 10, and 14 days for solutions
      stored at 4 degrees C; 0, 1, 2, 3, 8, and 11 days for solutions stored at 25
      degrees C; and 0, 6, 12, and 24 hours for solutions stored at 37 degrees C. The
      cefazolin concentration in both solutions was greater than or equal to 90% of the
      initial concentration for 14 days at 4 degrees C, 8 days at 25 degrees C, and 1
      day at 37 degrees C. On day 11 at 25 degrees C, however, the loss of cefazolin
      was 11% for the solution containing 1.5% dextrose injection and 15% for the 4.25%
      dextrose injection. The sterility of the solutions was not determined. Cefazolin
      sodium was stable in peritoneal dialysis solutions containing 1.5% and 4.24%
      dextrose injection for 14 days at 4 degrees C, 8 days at 25 degrees C, and 24
      hours at 37 degrees C.

PMID- 2003504
TI  - Stability of an extemporaneously compounded terbutaline sulfate oral liquid.
AB  - The stability of terbutaline sulfate in an extemporaneous oral liquid formulation
      refrigerated for 55 days was studied. A suspension was prepared by grinding
      commercially available 5-mg terbutaline sulfate tablets, adding Purified Water,
      USP, to form a paste, and then adding Simple Syrup, NF. A control solution was
      prepared from analytical grade terbutaline sulfate powder in Simple Syrup, NF.
      The final concentration of terbutaline sulfate in both preparations was 1 mg/mL.
      Three samples of each formulation were stored in 4-ounce amber glass prescription
      bottles in the dark at 4 degrees C. Immediately after preparation and at 10, 19,
      35, and 55 days, samples were visually inspected, tested for pH, and assayed in
      duplicate by high-performance liquid chromatography. On days 0 and 35, 100-microL
      samples of each suspension and solution were placed on agar plates for
      microbiological testing. On day 55, the mean percentages of the initial
      terbutaline sulfate concentrations remaining were 103.8% in the suspension and
      91.7% in the solution. Color, odor, and pH of the samples did not change
      appreciably, and colony counts of bacteria were within acceptable limits. An
      extemporaneously prepared liquid preparation of terbutaline sulfate in Simple
      Syrup, NF, is stable under the conditions studied for up to 55 days; however,
      since microbiological testing was not performed on day 55, it is recommended that
      the preparation be stored for no longer than 30 days.

PMID- 2003505
TI  - Responding to a physician's request to mislabel a patient's prescription.

PMID- 2003506
TI  - Multiattribute evaluation in formulary decision making as applied to calcium
      channel blockers.
AB  - The use of multiattribute utility theory (MAUT) to make a formulary decision
      involving calcium-channel blockers (CCBs) is described. The MAUT method is a
      procedure for identifying, characterizing, and comparing the many variables that
      may affect a decision. Although applications in pharmacy have been infrequent,
      MAUT should be particularly appealing to formulary committees. The steps of the
      MAUT method are (1) determine the viewpoint of the decision makers, (2) identify
      the decision alternatives, (3) identify the attributes to be evaluated, (4)
      identify the factors to be used in evaluating the attributes, (5) establish a
      utility scale for scoring each factor, (6) transform the values for each factor
      to its utility scale, (7) determine weights for each attribute and factor, (8)
      calculate the total utility score for each decision alternative, (9) determine
      which decision alternative has the greatest total score, and (10) perform a
      sensitivity analysis. The viewpoint of a formulary committee in a health
      maintenance organization was simulated to develop a model for using the MAUT
      method to compare CCBs for single-agent therapy of chronic stable angina in
      ambulatory patients for one year. The attributes chosen were effectiveness,
      safety, patient acceptance, and cost and weighted 36%, 29%, 21%, and 14%,
      respectively, as contributions to the evaluation. The rank order of the decision
      alternatives was (1) generic verapamil, (2) brand-name verapamil, (3) diltiazem,
      (4) nicardipine, and (5) nifedipine. The MAUT method provides a standardized yet
      flexible format for comparing and selecting among formulary alternatives.

PMID- 2003507
TI  - ASHP guidelines on pharmaceutical services for ambulatory patients.

PMID- 2003508
TI  - ASHP guidelines for the use of investigational drugs in organized health-care
      settings.

PMID- 2003509
TI  - ASHP technical assistance bulletin on surgery and anesthesiology pharmaceutical
      services.

PMID- 2003510
TI  - Considerations in employing a pharmacist recovering from chemical dependence.

PMID- 2003511
TI  - Herpes zoster in patients with rheumatoid arthritis treated with weekly, low-dose
      methotrexate.
AB  - PURPOSE: Herpes zoster occurred in nine patients with methotrexate-treated
      rheumatoid arthritis. We compared these patients to a large group of methotrexate
      treated rheumatoid arthritis patients in order to uncover potential factors
      explaining the occurrence of herpes zoster. PATIENTS AND METHODS: Data from 187
      patients taking methotrexate were reviewed and compared with data from another
      nine patients who developed herpes zoster while taking the drug for rheumatoid
      arthritis, all from the same university-based arthritis clinic. Literature
      pertinent to infection in rheumatoid arthritis patients treated with methotrexate
      is reviewed. RESULTS: Herpes zoster occurred in 14.5 cases per 1,000 patient
      years in our methotrexate-treated rheumatoid arthritis patients, as compared with
      the general population incidence of 1.3 to 4.8 cases per 1,000 patient-years. The
      infection was unrelated to duration of methotrexate usage, prednisone treatment,
      or the co-existence of diabetes mellitus, but appeared to occur in patients with
      high titers of rheumatoid factor and an overall longer duration of rheumatoid
      arthritis. There were no cases of systemic dissemination or recurrence of herpes
      zoster despite 27.4 years cumulative follow-up on continued methotrexate therapy.
      CONCLUSIONS: Herpes zoster may occur more frequently in patients with rheumatoid
      arthritis treated with low-dose methotrexate than in the general population.
      Herpes zoster in rheumatoid arthritis patients treated with methotrexate appears
      to be self-limited, benign, and statistically related to methotrexate use in the
      presence of longer-term rheumatoid disease.

PMID- 2003512
TI  - Benefit of ketotifen in patients with eosinophilic gastroenteritis.
AB  - PURPOSE: Eosinophilic gastroenteritis (EG) is a rare condition of unknown
      etiology characterized by vomiting, diarrhea, protein-losing enteropathy, and
      eosinophilic infiltration of the gastrointestinal mucosa. The potential
      association of EG with allergy and related mast-cell release of mediators led us
      to evaluate the ability of an antihistamine drug to modify the course of the
      disease. PATIENTS AND METHODS: Six patients with protracted gastrointestinal
      symptoms were diagnosed with EG because of histologic evidence of predominantly
      eosinophilic infiltrates in the gastrointestinal mucosa. Each patient was treated
      in an open trial for 12 months with ketotifen (Zaditen), an antihistamine of the
      H1 class that is known to stabilize mast cells. RESULTS: All six patients
      improved clinically; four also gained weight. Total serum IgE levels decreased
      after 4 to 6 months of therapy. Clearing of eosinophilic infiltrates was
      documented in the four patients who underwent follow-up mucosal biopsies.
      CONCLUSION: We conclude that ketotifen treatment represents a safe and effective
      alternative to traditional systemic corticosteroid therapy for treatment of EG.

PMID- 2003513
TI  - The occupational history in the primary care setting.
AB  - PURPOSE: To assess the need for services in occupational medicine, we determined
      the prevalence of reported occupational exposures in patients seen in the primary
      care setting. In addition, we evaluated the validity of our survey instrument.
      PATIENTS AND METHODS: All patients (n = 1,112) seen over a 3-month period of time
      in the Primary Care Clinic at the Iowa City Veterans Affairs Medical Center were
      considered eligible for this study. A survey instrument was developed to obtain
      specific information regarding occupational exposures. The questionnaire was
      administered to 534 or 48% of all eligible patients. The validity of the survey
      instrument was evaluated by comparing chest radiographs in subjects with a
      history of exposure to asbestos, coal dust, or silica to those in patients who
      were not exposed to any of these agents. RESULTS: We found that almost 75% of the
      patients reported prior occupational exposure to at least one potentially toxic
      agent, and over 30% claimed exposure to at least four potentially toxic agents.
      The validation study indicated that the reported exposure history for asbestos,
      coal dust, and silica is significantly associated with anticipated changes on
      chest radiographs. These findings suggest that this easily administered survey
      instrument is valid for pneumoconiotic dust exposures and may also be valid for
      other potentially toxic exposures. CONCLUSION: Data from our study indicate that
      patients seen in the ambulatory care setting may have clinically significant
      occupational exposures that are relevant to their medical condition.

PMID- 2003514
TI  - A patient-completed screening instrument for functional disability in the
      elderly.
AB  - PURPOSE: Although multi-disciplinary geriatric assessment of elderly patients has
      been shown to be effective in identifying new diagnoses and previously unknown
      disabilities and in decreasing hospitalization and mortality, time and financial
      constraints prevent most internists and office practitioners from using this
      approach with their older patients. Several instruments to screen older persons
      for functional disability have been proposed, but there are limited data
      regarding their utility or effectiveness in clinical medicine. This study
      developed a short, patient-completed screening assessment instrument (the
      Functional Assessment Screen), compared it to a standard, multi-disciplinary
      geriatric evaluation, and determined the screening instrument's ability to
      predict future use of home care services in a group of elderly patients. PATIENTS
      AND METHODS: The screening instrument was piloted retrospectively using data from
      patients seen in the previous 2 years at a hospital-based geriatrics clinic in
      Wisconsin. Using these results, a revised instrument was developed and mailed to
      80 consecutive new patients who presented to the clinic for multi-disciplinary
      geriatric assessment and primary care. These patients were interviewed 18 months
      later to determine use of home services, institutionalization, and death after
      the initial visit. RESULTS: Fifty-eight of 80 eligible patients (72%) completed
      both the clinic evaluation and 18-month follow-up. The patients were an elderly
      (mean age of 76), frail (average of three medical diagnoses), functionally
      disabled group (dependent in an average of 3.7 instrumental activities of daily
      living and 2.7 activities of daily living). Nine of the 58 enrolled patients
      (15%) were institutionalized, five (9%) died, and 31 (53%) required new home
      services after 18 months. The screening variables were sensitive but less
      specific than clinic providers' judgment in identifying abnormalities in social,
      economic, or physical health status. The relative risk of eventual home service
      use was elevated in patients reporting poor health status (relative risk of 3.5,
      95% confidence interval [CI] 9.9 to 1.2), and dependency in housework (relative
      risk of 3.0, 95% CI 5.1 to 1.7), shopping (relative risk of 2.6, 95% CI 4.7 to
      1.5), meals (relative risk of 2.4, 95% CI 3.4 to 1.7), dressing (relative risk of
      2.2, 95% CI 3.0 to 1.6), or bathing (relative risk of 2.2, 95% CI 3.2 to 1.5).
      Home services were used in 16% of patients with no positive responses to a subset
      of four of the screening questions; usage rose to 22% with one positive response,
      and to 89% (relative risk of 4.5, 95% CI 9.2 to 2.1) with two or more positive
      responses. CONCLUSIONS: This screening instrument identified a group of elderly
      patients at much higher risk for increased home service use than other patients
      in a geriatrics clinic. If validated in other populations, such an instrument may
      identify frail, elderly patients in office practice at high risk for use of home
      services. These patients could be targeted for more complete multi-disciplinary
      geriatric assessment to identify and treat disease and disability responsible for
      increased service use and declining health.

PMID- 2003516
TI  - Infection in the myelodysplastic syndromes.
AB  - PURPOSE: To determine the incidence, characteristics, and outcome of infection in
      patients with myelodysplastic syndromes (MDS) and risk factors that may lead to
      infection. PATIENTS AND METHODS: We reviewed infections that occurred in 86
      consecutive patients with MDS who received care from 1968 to 1986 at a university
      affiliated Veterans Affairs Medical Center. Time lines charting the course of
      each patient with MDS were created and included infections, MDS subgroup at the
      time of presentation and at the time of each infection, peripheral neutrophil
      counts, and therapies for MDS. RESULTS: Infections occurred at a rate of nearly
      one per patient year of observation. Infection rates were associated with MDS
      subgroup as follows: refractory anemia with or without ringed sideroblasts (RA +/
      RS) less than refractory anemia with excess blasts (RAEB) less than RAEB in
      transformation (RAEB-T). The group of RA +/- RS patients who had erythroid
      abnormalities but minimal or no dyspoiesis of other cell lines had the lowest
      rate of infections. Infection rates were higher in patients with less than or
      equal to 1,000 neutrophils/microL blood than in patients with greater than 1,000
      neutrophils/microL blood for each classifiable MDS subgroup. Neutrophil
      concentration and MDS subgroup were independent risk factors for infection in
      patients with MDS. Bacterial pneumonias and skin abscesses were the most common
      infections. Infection was the most common cause of death during MDS, accounting
      for 64% of deaths, and was more common than transformation to acute leukemia as a
      cause of death. CONCLUSION: Infection is a common, life-threatening problem in
      patients with MDS. Neutropenia and MDS subgroup are each risk factors for
      infection. Clinicians should aggressively evaluate patients with fever and MDS
      for infection, especially pneumonia and skin infections.

PMID- 2003515
TI  - Small non-cleaved-cell lymphoma (undifferentiated lymphoma, Burkitt's type) in
      American adults: results with treatment designed for acute lymphoblastic
      leukemia.
AB  - PURPOSE: Small non-cleaved-cell lymphoma (SNCL) "Burkitt's type," a rapidly
      growing lymphoma, has been rare among adults in the United States, but has
      greatly increased in incidence with the acquired immunodeficiency syndrome
      epidemic. This report details the results of treatment of adult SNCL with a
      series of protocols originally designed for the treatment of acute lymphoblastic
      leukemia (ALL). PATIENTS AND METHODS: Between July 1973 and May 1987, 29 adults
      with newly diagnosed SNCL were treated at Memorial Hospital with intensive
      chemotherapy originally designed for ALL: the cyclophosphamide L-2, L-10, L-17,
      and L-20 protocols. Nine patients had positive serologies for human
      immunodeficiency virus (HIV) infection. One patient with all measurable disease
      resected was not evaluable for response. RESULTS: Sixteen of 28 evaluable
      patients (57%) achieved a complete remission with treatment. With follow-up as
      long as 153 months (median, 47 months), 50% of all patients and 59% of patients
      with negative or unknown HIV serologies have survived and are probably cured.
      Patients with an initial serum lactic acid dehydrogenase (LDH) level of greater
      than 500 U/L had a significantly shortened survival as compared with those with a
      lower serum LDH. Other pretreatment patient characteristics associated with a
      shortened survival of borderline statistical significance were high National
      Cancer Institute stage (C, D) and bone marrow involvement. These results are
      similar to those for ALL and lymphoblastic lymphoma and are comparable to those
      for American SNCL in the literature. CONCLUSIONS: Approximately one half of
      adults with SNCL are curable with intensive chemotherapy. More intensive
      chemotherapy with hematopoietic growth factor and/or autologous bone marrow or
      peripheral stem cell support may increase curability.

PMID- 2003517
TI  - A model to predict multivessel coronary artery disease from the exercise thallium
      201 stress test.
AB  - PURPOSE: The aim of this study was to (1) determine whether nonimaging variables
      add to the diagnostic information available from exercise thallium-201 images for
      the detection of multivessel coronary artery disease; and (2) to develop a model
      based on the exercise thallium-201 stress test to predict the presence of
      multivessel disease. PATIENTS AND METHODS: The study populations included 383
      patients referred to the University of Virginia and 325 patients referred to the
      Massachusetts General Hospital for evaluation of chest pain. All patients
      underwent both cardiac catheterization and exercise thallium-201 stress testing
      between 1978 and 1981. RESULTS: In the University of Virginia cohort, at each
      level of thallium-201 abnormality (no defects, one defect, more than one defect),
      ST depression and patient age added significantly in the detection of multivessel
      disease. Logistic regression analysis using data from these patients identified
      three independent predictors of multivessel disease: initial thallium-201
      defects, ST depression, and age. A model was developed to predict multivessel
      disease based on these variables. As might be expected, the risk of multivessel
      disease predicted by the model was similar to that actually observed in the
      University of Virginia population. More importantly, however, the model was
      accurate in predicting the occurrence of multivessel disease in the unrelated
      population studied at the Massachusetts General Hospital. CONCLUSION: It is,
      therefore, concluded that (1) nonimaging variables (age and exercise-induced ST
      depression) add independent information to thallium-201 imaging data in the
      detection of multivessel disease; and (2) a model has been developed based on the
      exercise thallium-201 stress test that can accurately predict the probability of
      multivessel disease in other populations.

PMID- 2003518
TI  - Bone mineral density in postmenopausal women treated with L-thyroxine.
AB  - PURPOSE: To determine if bone mineral density is decreased in postmenopausal
      women treated with 1-thyroxine, and, if any decrease is observed, whether it is
      related to overtreatment with thyroid hormone, to deficiency of calcitonin, or to
      other factors. PATIENTS AND METHODS: The study consisted of 19 postmenopausal
      women between 50 and 75 years of age treated with 1-thyroxine for 5 years or
      longer, and 19 matching control subjects with no thyroid disease. Bone mineral
      density of the spine and hip was measured by dual-photon absorptiometry. Plasma
      calcitonin concentrations and serum thyroid hormone levels were determined by
      radioimmunoassays. RESULTS: The 1-thyroxine-treated women had lower bone density
      in the lumbar spine (1.013 g/cm2 [95% confidence interval, 0.945 to 1.081] versus
      1.134 g/cm2 [1.026 to 1.242], p = 0.043); in the femoral neck (0.736 g/cm2 [0.694
      to 0.778] versus 0.809 g/cm2 [0.747 to 0.872], p = 0.040); in Ward's triangle
      (0.576 g/cm2 [0.530 to 0.623] versus 0.694 g/cm2 [0.617 to 0.770], p = 0.011);
      and in the trochanteric area (0.626 g/cm2 [0.581 to 0.672] versus 0.722 g/cm2
      [0.651 to 0.794], p = 0.027). The maximal increase in calcitonin following
      calcium infusion was 1.37 ng/L (95% confidence interval, -0.44 to 3.17) in the 1
      thyroxine-treated patients versus 18.8 ng/L (95% confidence interval, 10.0 to
      27.5) in normal women, p less than 0.001. The average dose of 1-thyroxine was 120
      micrograms/day; 16 of the 19 patients had normal serum thyroxine levels. However,
      TSH levels were low in 13 of the 19, suggesting that 1-thyroxine treatment was
      supraphysiologic. Seven of the 19 patients had a history of hyperthyroidism in
      the distant past; these patients, considered separately, had significantly
      reduced bone density in the hip. The other 12 patients, considered separately,
      did not have a statistically significant loss of bone density. CONCLUSIONS: Long
      term 1-thyroxine therapy is associated with decreased density of the spine and
      hip. Since subclinical hyperthyroidism, decreased calcitonin responsiveness, and
      a history of hyperthyroidism were demonstrated in some or all of these patients,
      these factors must be considered as possible causes of the decreased bone
      density.

PMID- 2003519
TI  - Percutaneous transluminal coronary angioplasty in hypothyroidism.
AB  - PURPOSE: To determine the risks of percutaneous transluminal coronary angioplasty
      (PTCA) in hypothyroid individuals. PATIENTS AND METHODS: In a retrospective
      cohort study, 13 patients with primary hypothyroidism were identified among 382
      consecutive PTCA cases in 1987. Twenty-two euthyroid PTCA control subjects and 13
      hypothyroid patients who underwent coronary artery bypass surgery (CAB) were
      identified for comparison. RESULTS: Hypothyroid and euthyroid PTCA patients had
      similar mean ages, numbers of prior and recent acute myocardial infarctions,
      diseased coronary arteries, coronary arteries dilated, and serum cholesterol
      levels. There were no significant differences in procedure-related mortality (0%
      versus 0%); coronary artery dissection (23% versus 23%); reocclusion (8% versus
      5%); bradycardia (0% versus 0%); heart failure (0% versus 5%); hypotension (31%
      versus 27%); myocardial infarction (8% versus 0%); gastrointestinal dysfunction
      (0% versus 0%); neuropsychiatric disturbance (15% versus 9%); hyponatremia (23%
      versus 23%); hypothermia (0% versus 0%); or fever (15% versus 5%). Hematoma
      formation tended to be more frequent in the hypothyroid group (38% versus 18%, p
      = 0.18). Similar results were obtained when the subgroup of more severely
      hypothyroid patients (thyrotropin level more than 20 mU/L, n = 7) was examined.
      Compared to hypothyroid CAB patients, hypothyroid PTCA patients had less
      incidence of heart failure (0% versus 31%, p less than 0.025); neuropsychiatric
      disturbance (15% versus 54%, p less than 0.025); hyponatremia (23% versus 62%, p
      less than 0.05); gastrointestinal dysfunction (0% versus 23%, p less than 0.025);
      and fever (15% versus 62%, p less than 0.001). CONCLUSION: PTCA can be performed
      in hypothyroid patients without increased mortality or major morbidity, and when
      appropriate, may be preferred to bypass surgery for coronary revascularization in
      patients intolerant of full thyroid hormone replacement.

PMID- 2003520
TI  - Academic physicians: today's dinosaurs?

PMID- 2003521
TI  - Acute renal failure associated with the use of intraperitoneal carboplatin: a
      report of two cases and review of the literature.
AB  - Carboplatin, a new analogue of cisplatin used in the treatment of ovarian
      carcinoma, has been demonstrated to be less nephrotoxic than its predecessor. To
      date, hundreds of cycles of therapy have been given without a significant
      incidence of renal failure. We report herein two cases of acute, nonoliguric
      renal failure in patients receiving intraperitoneal (IP) carboplatin as
      chemotherapy for advanced ovarian carcinoma. Each patient had received extensive
      previous treatment with cisplatin. The baseline serum creatinine levels in the
      patients were 0.9 and 1.1 mg/dL, respectively. After four cycles of IP
      carboplatin in Patient 1 and five cycles of IP carboplatin in Patient 2, the
      serum creatinine levels abruptly rose to 9.0 and 9.5 mg/dL, respectively, within
      a week after administration of therapy. No other primary etiologies for acute
      renal failure could be identified in either patient. One patient required
      hemodialysis briefly. Renal biopsy specimens were obtained from both patients.
      Patient 1 had focal and moderate interstitial nephritis with mild periglomerular
      fibrosis. Patient 2 had an edematous interstitium with a diffuse mononuclear cell
      infiltrate, focal interstitial hemorrhage, and toxic changes in proximal and
      distal tubules on electron microscopy. Treatment with oral prednisone at 1
      mg/kg/day with a rapid taper over 4 weeks was done in both cases with the serum
      creatinine levels eventually dropping to 4.6 and 2.0 mg/dL, respectively. Acute
      interstitial nephritis and renal failure to this extent have not been previously
      reported with carboplatin therapy. The literature regarding carboplatin is
      reviewed with respect to the pathophysiology of its nephrotoxicity.

PMID- 2003522
TI  - Bacterial endocarditis presenting as acute myocardial infarction: a cautionary
      note for the era of reperfusion.
AB  - Coronary embolism is a known complication of bacterial endocarditis that
      sometimes causes acute myocardial infarction. The necessity for rapidly restoring
      coronary artery perfusion and the time constraints governing clinical decisions
      may prevent endocarditis from being diagnosed before pharmacologic or mechanical
      thrombolysis. This report describes the first documented cases of coronary
      angioplasty in two patients with acute myocardial infarction caused by bacterial
      endocarditis, and reviews the literature on coronary artery complications of
      bacterial endocarditis. The first patient developed a coronary artery mycotic
      aneurysm at the dilatation site; the second experienced a small intracerebral
      hemorrhage following reperfusion. It is, of course, unwise to generalize from two
      cases, but we believe that in patients who are most likely to have endocarditis
      as the cause of acute myocardial infarction, the impulse to follow conventional
      strategies for coronary reperfusion should be tempered by thoughts of possible
      consequences.

PMID- 2003523
TI  - Use of recombinant human erythropoietin to enhance autologous blood donation in a
      patient with multiple red cell allo-antibodies and the anemia of chronic disease.
AB  - We treated a patient with alcohol-induced cirrhosis, intractable pain from a
      defective hip prosthesis, and multiple red cell allo-antibodies with recombinant
      human erythropoietin (EPO) in order to facilitate collection of blood for
      autologous transfusion during an elective total hip revision. This patient had
      experienced a delayed transfusion reaction 4 months earlier after receiving least
      incompatible packed red cells for gastrointestinal bleeding. His blood could not
      be crossmatched because of the development of multiple antibodies to homologous
      blood given during previous surgery and several episodes of gastrointestinal
      hemorrhage. Following initiation of EPO therapy, there was a prompt and
      persistent increase in the reticulocyte count from a baseline of 1.6% to a
      maximum of 8.6%. This was accompanied by maintenance of the hematocrit between
      32% and 38.5% despite withdrawal of seven units of autologous blood over the 45
      day treatment period. Poor venous access and availability of blood bank
      personnel, not hematocrit level, were the limiting factors that determined how
      frequently blood could be collected. We conclude that EPO stimulated
      erythropoiesis in this patient with underlying anemia of chronic disease and
      facilitated harvest of autologous blood for elective surgery.

PMID- 2003524
TI  - Successful acyclovir therapy of severe varicella hepatitis in an adult renal
      transplant recipient.

PMID- 2003525
TI  - Diltiazem-cyclosporine interaction in cardiac transplant recipients: impact on
      cyclosporine dose and medication costs.

PMID- 2003526
TI  - Resetting of the vasopressin osmostat during infectious pneumonia.

PMID- 2003527
TI  - Rapid correction of hyponatremia in psychiatric patients with polydipsia.

PMID- 2003528
TI  - Fever in patients with crystal-induced arthritis.

PMID- 2003529
TI  - Streptokinase therapy and breakaway pulmonary emboli.

PMID- 2003530
TI  - Posterior colporrhaphy and perineorrhaphy: separate and distinct operations.
AB  - Posterior vaginal repair is often poorly understood and ineffectively performed.
      The goals of reconstructive surgery emphasize relief of symptoms and restoration
      of normal anatomic relationships and of function. A useful method to
      preoperatively determine posterior vaginal wall weakness is outlined along with a
      surgical description of important steps in surgical reconstruction.

PMID- 2003531
TI  - Stratification and standards: a quality assurance perspective. Presidential
      address.
AB  - A diminished public respect for physicians, a decrease in professional autonomy,
      and an increased regulatory presence have led to extensive changes in medical
      practice in the past 25 years. Along with rising costs of medical care, there has
      been a resurgence in interest in the quality of health care, and a considerable
      body of literature on the monitoring and evaluation of health services has been
      produced. Quality assurance programs frequently evoke negative and skeptical
      responses from many physicians for a variety of reasons. Crucial to the potential
      effectiveness of quality assessment methods is the setting of standards.
      Physician clinicians should be strongly encouraged to participate directly and
      seriously in the development of standards. The quality assurance process should
      be viewed by physicians as an opportunity to recapture the control of the
      profession and to demonstrate to patients, in an objective manner, the legitimate
      high quality of care rendered.

PMID- 2003532
TI  - Antepartum cultures for Ureaplasma urealyticum are not useful in predicting
      pregnancy outcome. The Vaginal Infections and Prematurity Study Group.
AB  - To test the hypothesis that genital colonization with Ureaplasma urealyticum
      would predict adverse pregnancy outcome, 4934 women from five medical centers
      were evaluated for vaginal colonization with U. urealyticum between 23 and 26
      weeks' gestation and followed up to delivery. U. urealyticum colonization was
      associated with maternal age, parity, racial-ethnic group, martial status,
      income, education, smoking, number of sexual partners, and colonization with
      Trichomonas vaginalis, Mycoplasma hominis, and bacterial vaginosis. After
      adjustment for medical and sociodemographic factors in a multivariate analysis,
      there was no difference in the mean birth weight or proportion of low-birth
      weight infants delivered by women who carried U. urealyticum and those who did
      not. U. urealyticum colonization at 23 to 26 weeks was not associated with
      preterm rupture of membranes, preterm labor, or preterm delivery. A positive
      vaginal culture for U. urealyticum in midgestation does not predict those women
      at risk for preterm labor, preterm delivery, preterm premature rupture of
      membranes, or delivery of a low-birth-weight infant.

PMID- 2003533
TI  - A randomized placebo-controlled trial of erythromycin for the treatment of
      Ureaplasma urealyticum to prevent premature delivery. The Vaginal Infections and
      Prematurity Study Group.
AB  - Ureaplasma urealyticum has been associated with low birth weight and histologic
      chorioamnionitis and it is a frequent isolate from the chorioamnion of patients
      who are delivered prematurely. In prior clinical trials using antibiotics active
      against U. urealyticum, antibiotic treatment was associated with reduced
      prematurity and increased mean birth weight. In this multicenter, randomized,
      double-blind clinical trial, pregnant women with U. urealyticum were treated with
      333 mg of erythromycin base or placebo three times daily, starting between 26 and
      30 weeks' gestation and continuing through 35 completed weeks of pregnancy. Women
      with urinary tract infection or Neisseria gonorrhoeae infection were excluded
      from the trial, and women with Chlamydia trachomatis or group B streptococci were
      excluded from these analyses. Erythromycin did not eliminate U. urealyticum from
      the lower genital tract. There were no significant differences between
      erythromycin- and placebo-treated women in infant birth weight or gestational age
      at delivery, in frequency of premature rupture of membranes, or in neonatal
      outcome.

PMID- 2003534
TI  - Evaluation of an aneurysm of the vein of Galen in utero by pulsed and color
      Doppler ultrasonography.

PMID- 2003535
TI  - Epidermal growth factor receptor expression in normal ovarian epithelium and
      ovarian cancer. II. Relationship between receptor expression and response to
      epidermal growth factor.
AB  - Previously we have shown that epidermal growth factor acts as a mitogen for some,
      but not all, ovarian cancer cells in culture. In this study we examined the
      effect of epidermal growth factor on proliferation of normal human ovarian
      epithelial cells in monolayer culture. We found that epidermal growth factor
      stimulated twofold to fourfold increases in proliferation in epithelial cells
      from each of five normal ovaries (p less than 0.01). In addition, Scatchard
      analysis of binding of epidermal growth factor tagged with iodine 125 indicated
      the presence of high-affinity receptors in all of the ovarian epithelial cells
      and ovarian cancer cell lines. The number and affinity of receptors was similar
      in the normal epithelium and cancer cell lines, and there was no relationship
      between epidermal growth factor receptor number and responsiveness to epidermal
      growth factor. We conclude that human ovarian epithelial cells normally express
      epidermal growth factor receptors and that epidermal growth factor acts as a
      mitogen for these cells. Although the mitogenic response to epidermal growth
      factor often is attenuated in ovarian cancer cell lines, loss of responsiveness
      to epidermal growth factor does not appear to be due to decreased receptor
      expression.

PMID- 2003536
TI  - Prenatal diagnosis of myotonic muscular dystrophy with linked deoxyribonucleic
      acid probes.
AB  - Since the localization of the myotonic muscular dystrophy gene, closer
      deoxyribonucleic acid markers have been discovered. These now facilitate both
      presymptomatic and prenatal diagnosis of myotonic muscular dystrophy. We report
      our prenatal diagnosis experience with six cases in five families. Obstetricians
      are advised to inform their patients with a family history of myotonic muscular
      dystrophy of these testing opportunities. The fetus of the mother with myotonic
      muscular dystrophy who remains in utero until term is at considerable risk, as is
      the mother herself, of serious obstetric complications.

PMID- 2003537
TI  - Prevention of preterm birth in high-risk patients: the role of education and
      provider contact versus home uterine monitoring.
AB  - A total of 394 patients were enrolled in a study to assess the effectiveness of
      an educational preterm delivery prevention program and to determine whether the
      addition of home uterine monitoring to the program improved results in patients
      at high risk of preterm labor. Both the educational program and home uterine
      monitoring were found to increase the percentage of women with preterm labor who
      sought care while still favorable for long-term suppression, resulting in a
      decreased incidence of preterm births and improved outcome when compared with
      similar high-risk patients who did not participate in these programs. In a
      randomized, prospective study, addition of home uterine monitoring to the
      educational program was found to significantly improve outcome in twin gestations
      but not in singleton gestations. However, the number of singleton pregnancies was
      too small to rule out possible benefit from home uterine monitoring in that
      group.

PMID- 2003538
TI  - Impact of tubal sterilization and vasectomy on female marital sexuality: results
      of a controlled longitudinal study.
AB  - To determine if female or male sterilization affects long-term female marital
      sexuality, we prospectively compared baseline data and 5 consecutive years of
      follow-up data from 152 tubal sterilization women, 106 vasectomy wives, and 83
      women not planning sterilization. By follow-up year 5, no group of women
      expressed any change in satisfaction with their own sexual response; however, all
      groups showed a significant decrease across time in satisfaction with their
      sexual relationship, in coital desire, and in coital frequency. There were no
      group differences in overall net changes or in rates of change over the 5-year
      period. However, two short-term group differences were noted: a decrease in
      coital desire among women not planning sterilization between baseline and follow
      up year 4, compared with increases for both sterilization groups, and an increase
      in coital frequency at the first follow-up year only in the tubal sterilization
      group. These data indicate that there are no detrimental effects and some short
      term benefits of both sterilization procedures on female marital sexuality.

PMID- 2003539
TI  - The "Allis" test for easy cesarean delivery.
AB  - Cesarean delivery may be complicated by dystocia if the incision size is
      inadequate. A test is described that may be easily applied at cesarean section,
      creating greater objectivity in the determination of surgical incision size. One
      hundred patients were studied prospectively. Patients with incisions that passed
      the test had a shorter mean time of delivery and less difficult deliveries than
      those of patients with incisions that failed the test. We conclude that the
      "Allis" test is a simple way to reduce the incidence of dystocia at cesarean
      delivery.

PMID- 2003540
TI  - Recurrent herpes gestationis with postpartum flare: a case report.
AB  - A case of herpes gestationis recurring in each pregnancy, with a postpartum flare
      up in the last pregnancy, is described. The diagnosis was confirmed by skin
      biopsy. The first pregnancy ended in a term stillbirth, but there were favorable
      outcomes in four subsequent pregnancies. Histopathologic examination of the
      placentas of the last three pregnancies revealed varying grades of villositis.
      Symptoms improved with oral corticosteroids.

PMID- 2003541
TI  - Transvaginal color Doppler imaging in the assessment of uteroplacental blood flow
      in the normal first-trimester pregnancy.
AB  - Characteristic changes of low resistance and high diastolic blood flow velocity
      were identified by Doppler studies starting in the early phase of the second
      trimester. These changes were attributed by some authors to trophoblastic
      invasion of the uterine vasculature converting the uterus into a low-resistance
      organ. Because of technical limitations previous studies were confined to the
      uterine artery and its main branches. With the development of color Doppler and
      transvaginal ultrasonography we can now identify blood flow in various small
      vessels in the placental bed. This study was performed to assess the ability of
      color Doppler ultrasonography to evaluate subtrophoblastic blood flow by color
      identification in the early phase of normal pregnancy from 5 to 9 weeks'
      gestation. Results show that the characteristic increase in diastolic blood flow
      is evident as early as 5 weeks' gestation.

PMID- 2003542
TI  - Small-for-gestational-age birth: maternal predictors and comparison with risk
      factors of spontaneous preterm delivery in the same cohort.
AB  - Low birth weight, the primary predictor of infant mortality and morbidity, can be
      a result of shortened gestation (preterm delivery) or fetal growth retardation
      (small for gestational age). We examined the relationship between maternal
      characteristics and the risk of delivering a small-for-gestational age infant in
      2228 women who participated in the University of California, San Diego Prenatal
      Nutrition Project between 1978 and 1988. A multivariate analysis indicated that
      significant risk factors for small for gestational age were cigarette smoking
      (odds ratio, 3.18), a low rate of maternal weight gain (odds ratio, 2.96), black
      ethnicity (odds ratio, 2.60), pregravid underweight (odds ratio, 2.36), Asian
      ethnicity (odds ratio, 1.88), primiparity (odds ratio, 1.85), and low maternal
      height (odds ratio, 1.63). These findings are contrasted with those previously
      published on preterm deliveries in the same cohort. We conclude that with the
      exception of black ethnicity and low maternal weight gain, different maternal
      characteristics were significantly associated with small-for-gestational-age and
      preterm birth in this population.

PMID- 2003543
TI  - Antisperm antibodies to sperm surface antigens in women with genital tract
      infection.
AB  - Antisperm antibodies to sperm surface antigens in nulligravid women with primary
      upper genital tract infections were measured by the sperm mixed agglutination
      reaction assay. As many as 56% of women with a primary episode of pelvic
      inflammatory disease had antisperm antibodies. In addition, 69% of those women
      with no history of genital tract infection but with laparoscopic evidence of past
      pelvic infection had significant levels of circulating antisperm antibodies.
      Electroimmunoblots of sperm preparations probed with the sera of women who had
      either known or presumed upper genital tract infection revealed a uniformly
      recognized 69 kd antigen. In contrast, women with circulating antisperm
      antibodies before primary upper genital tract infection recognized up to five
      distinct sperm antigen determinants of 27, 54, 131, 146, and 174 kd. It is a
      distinct possibility that genital tract infections may lead to immunopotentiation
      of antisperm antibodies that could affect fertility.

PMID- 2003544
TI  - Genotyping of macerated stillborn fetuses.
AB  - It is generally impossible to collect blood or to culture tissue from a macerated
      stillborn fetus. Accurate genotyping of such a fetus may, however, be critical
      for the diagnosis of genetic diseases and appropriate genetic counseling. In the
      East Flanders Prospective Twin Study, placental tissue of twin and triplet sets,
      in some of which one or both members were stillborn and macerated, has been
      stored at -20 degrees C. Of all these fetuses, sex and zygosity could be
      determined accurately on the placental deoxyribonucleic acid. We tested the
      possibility of nongenetic changes in deoxyribonucleic acid that result from
      maceration or tissue degradation over time in storage on placental samples from
      monochorionic twins in which only one member was stillborn and macerated. The
      deoxyribonucleic acid variants in these monozygotic twins were identical whether
      or not either cotwin was macerated. Thus deoxyribonucleic acid variants can be
      determined accurately on the placental tissue of macerated fetuses, even after
      prolonged freezing.

PMID- 2003545
TI  - Weight gain by gestational age in both black and white women delivered of normal
      birth-weight and low-birth-weight infants.
AB  - Although adequate maternal weight gain during pregnancy is widely acknowledged as
      a desirable goal, a contemporary standard for weight gain over the entire period
      of gestation based on a low-risk U.S. population has not been available.
      Information about usual weight gain in early pregnancy was particularly lacking.
      In a study monitoring various aspects of prenatal care in women in a population
      based case-control study of low birth weight, we collected information on weight
      gain at various gestational ages in the 281 women who had prenatal care and were
      delivered of infants at a prepaid health plan facility where standardized records
      were kept. In white women who were delivered of infants who weighed greater than
      or equal to 3000 gm, average weight gain was 5.3 pounds at 9 to 10 weeks'
      gestation, 10.5 pounds at 11 to 20 weeks, 24.2 pounds at 21 to 30 weeks, and 35.1
      pounds at 31 to 40 weeks. Weight gain among black women delivered of infants who
      weighed greater than or equal to 3000 gm was 4.2 pounds at 9 to 10 weeks'
      gestation, 14.8 pounds at 11 to 20 weeks, 24.5 pounds at 21 to 30 weeks, and 33.9
      pounds at 31 to 40 weeks. Weight gain was highly variable at all gestational ages
      in both black and white women. Weight gain in both black and white women
      delivered of infants with weights greater than or equal to 3000 gm was linear at
      a rate of about 0.66 pounds per week from 8 through 20 weeks' gestation and
      linear at a rate of 1.06 pounds per week after week 20.

PMID- 2003546
TI  - The effects of hormone replacement therapy in normal postmenopausal women:
      measurements of Doppler-derived parameters of aortic flow.
AB  - In this study the effects of hormone replacement therapy on cardiac function in
      healthy postmenopausal women were evaluated by Doppler echocardiography that was
      performed before (T1) and 2.5 months after the initiation of hormone replacement
      therapy (T2) in the peak estrogenic phase. The following parameters of aortic
      flow were measured: peak flow velocity, acceleration time, and ejection time.
      Additional parameters were calculated: flow velocity integral and mean
      acceleration. The study group included 24 postmenopausal women aged 43 to 60
      years (mean 51.6 years). The control group consisted of 19 postmenopausal women
      aged 46 to 60 years (mean 53.5 years) who were not receiving hormone replacement
      therapy and who underwent the same evaluation. There were no changes in all
      Doppler parameters between T1 and T2 in the control group. However, in the study
      group there were significant increases in peak flow velocity (108.3 +/- 16.7
      cm/sec at T1 vs 123 +/- 20.7 cm/sec at T2; p = 0.002), flow velocity integral
      (17.7 +/- 3.9 vs 21.5 +/- 4.7 cm; p = 0.0003), mean acceleration (11.5 +/- 1.9 vs
      13.1 +/- 2.6 m/sec/sec; p = 0.001), and ejection time (324 +/- 37.6 vs 348.8 +/-
      40.7 msec; p = 0.002). There was no change in acceleration time (94.8 +/- 6.6 vs
      95 +/- 10.9 msec). These results demonstrate that estrogens increase both stroke
      volume and flow acceleration. The latter probably reflects a combination of
      enhanced inotropism and vasodilatation. We assume that the cardioprotective
      effect of hormone replacement therapy in postmenopausal women may be due not only
      to changes in lipid profile but also to direct effects of estrogens on central
      and peripheral hemodynamic parameters.

PMID- 2003547
TI  - Amniotic fluid glucose and intraamniotic infection.
AB  - Thirty-nine patients with either premature labor and/or preterm premature
      ruptured membranes underwent transabdominal amniocentesis to enable the following
      amniotic fluid analyses to be performed: culture and sensitivity, Gram's stain,
      and glucose determination. All nine patients with intraamniotic infection had
      amniotic fluid glucose values less than 10 mg/dl. Three patients with amniotic
      fluid glucose levels less than 10 mg/dl but without chorioamnionitis were
      delivered of infants within 72 hours of admission. The mean amniotic fluid
      glucose level of patients with intraamniotic infection (5 +/- 2.4 mg/dl) was
      significantly lower than in those without intraamniotic infection (39.8 +/- 18.42
      mg/dl). All patients with amniotic fluid glucose values less than 10 mg/dl had
      either bacteria and/or white blood cells on Gram's stain. Two patients without
      chorioamnionitis had white cells on Gram's stain and amniotic fluid glucose
      values greater than 10 mg/dl. It appears that amniotic fluid glucose is more
      sensitive and more specific than Gram's stain in the diagnosis of intraamniotic
      infection. All 12 patients with low amniotic fluid glucose values were delivered
      of infants within 72 hours as the result of either the presence of infection or
      the progression of labor.

PMID- 2003548
TI  - Fetal breathing movements after preterm premature rupture of membranes.
AB  - Forty-three patients with preterm premature rupture of membranes were studied
      between 24 and 34 weeks' gestation. Intraamniotic infection was excluded by
      amniocentesis. There were significantly fewer fetal breathing movements for the
      first 2 weeks of membrane rupture, compared with controls, with a return to near
      normal by the third week. This reduction in fetal breathing may play a role in
      the production of pulmonary hypoplasia in some of these patients. Further studies
      are needed to investigate whether ruptured membranes are associated with a
      reduction in fetal breathing at earlier gestational ages.

PMID- 2003549
TI  - Outpatient sedation: an essential addition to gynecologic care for persons with
      mental retardation.
AB  - Routine gynecologic care for persons with mental retardation may be difficult to
      provide, especially to those women who do not allow a pelvic examination to be
      performed. Of 275 women referred to a multidisciplinary clinic addressing the
      reproductive health concerns of mentally retarded women, 61 patients (22%) did
      not allow a gynecologic examination to be performed. The administration of
      ketamine alone, midazolam alone, or a combination of midazolam and ketamine
      allowed for the successful performance of a gynecologic examination in 81% of
      previously uncooperative women. No adverse effects of the medications were noted.
      We conclude that sedation of difficult-to-examine, mentally handicapped women can
      be safely performed in the outpatient setting, thus avoiding the need for general
      anesthesia and its inherent risks.

PMID- 2003550
TI  - Cardiac function in fetuses of type I diabetic mothers.
AB  - Cardiac function was cross-sectionally studied by means of M-mode and Doppler
      echocardiography in 40 fetuses of mothers with well-controlled insulin-dependent
      diabetes at 20 to 38 weeks of gestation. These variables were measured:
      interventricular septal thickness, ratio between the peak velocities during early
      passive ventricular filling and active atrial filling at the level of the
      atrioventricular valves, peak velocities, and the time to peak velocity at the
      level of the ascending aorta and the pulmonary artery. The values obtained were
      compared with our reference limits for gestation. A significant increase of
      interventricular septal thickness that was unrelated to maternal glycosylated
      hemoglobin levels was evidenced. Early passive ventricular filling/active atrial
      filling ratios were significantly lower in fetuses of diabetic mothers than in
      control fetuses. These differences were significantly related to interventricular
      septal thickness. No significant modifications were found in either aortic or
      pulmonary peak velocities or in time to peak velocity values. These findings
      suggest that in spite of an adequate metabolic control an interventricular septal
      hypertrophy that affects cardiac diastolic function develops in fetuses of
      diabetic mothers.

PMID- 2003551
TI  - Human placenta expresses endothelin gene and corresponding protein is excreted in
      urine in increasing amounts during normal pregnancy.
AB  - Systemic and renal hemodyanmic changes in normal pregnancy have been attributed
      in part to altered vascular synthesis of vasodilatory prostaglandins. Besides
      vasodilatory substances, endothelium also generates vasoconstrictors, including
      endothelin. We evaluated the capacity of placental tissue from normal pregnant
      women to express endothelin gene and to generate endothelin. Placental tissue
      expressed a single 2.3 kb preproendothelin messenger ribonucleic acid and
      produced comparable amounts of endothelin 3, Big endothelin 1, and endothelin 1
      and a minor quantity of endothelin 2. To investigate the possible influence of
      placental endothelin production on plasma levels of the peptide, plasma
      endothelin concentrations were measured in normal pregnant women at delivery and
      were found to be numerically higher than those measured in nonpregnant subjects.
      Urinary excretion of endothelin, taken as a marker of the renal synthesis of the
      peptide, tended to increase, although not significantly, in the first 14 weeks of
      pregnancy. This trend continued throughout pregnancy, resulting in a significant
      increase from the second trimester to delivery.

PMID- 2003552
TI  - Mild fetal lateral cerebral ventriculomegaly: clinical course and outcome.
AB  - The neonatal, pathologic outcome and karyotypic abnormalities are reported for 44
      fetuses with mild ventriculomegaly diagnosed antenatally. Seventeen of these 44
      fetuses (39%) had other ultrasonographic defects, and five (12%) had abnormal
      karyotypes. Five pregnancies were electively aborted and three other fetuses died
      in the neonatal period. Twenty-six (72%) of the remaining 36 live-born neonates
      are developmentally and clinically normal at 3 to 18 months of age. Twenty-one of
      these 26 had isolated mild ventriculomegaly as the only ultrasonographic finding.
      The other 10 live-born infants are developmentally impaired, and five of these 10
      had mild ventriculomegaly as the only prenatal ultrasonographic abnormality. In
      conclusion, these data show that fetuses with mild ventriculomegaly have a lower
      incidence of associated anomalies and a better outcome than fetuses with more
      severe ventricular dilatation, as reported in the literature. The majority of
      fetuses with mild ventriculomegaly as an isolated finding and a normal karyotype
      are developing normally.

PMID- 2003553
TI  - Hospital setting and fetal death during labor among women at low risk.
AB  - Intrapartum fetal death in low-risk women at term is a rare obstetric outcome.
      This is difficult to study because few data sets contain an adequate number of
      cases for meaningful analysis. This study used data from the 1980 National
      Natality Survey and National Fetal Mortality Survey, merged with an American
      Hospital Association annual survey for the same year, to determine whether the
      frequency of intrapartum fetal death in low-risk women varied by the hospital
      setting for birth. Stratified analysis was used to assess the relation of level
      of hospital for delivery with intrapartum fetal death, with control for potential
      confounding factors. As the level of available perinatal technology decreased,
      the frequency of intrapartum fetal death increased (odds ratio, 2.0 for Level II
      and 3.3 for Level I, as compared with Level III hospitals). Even when early
      neonatal deaths were considered, perinatal mortality remained lowest at Level III
      facilities (odds ratio, 1.6 for Level II and 2.7 for Level I, as compared with
      Level III hospitals). The components of intrapartum surveillance that are most
      effective in the reduction of perinatal mortality have not been identified.

PMID- 2003554
TI  - Fetal ovarian cysts: prenatal ultrasonographic detection and postnatal evaluation
      and treatment.
AB  - Ovarian cysts were diagnosed by antenatal ultrasonographic examination in 15
      fetuses between 19 and 37 weeks' gestation. In six cases there was
      ultrasonographic evidence of torsion. Intracystic flocculation, which typically
      was deposited on the sloping part of the cyst, gave a characteristic liquid
      interface that was regarded as ultrasonographic evidence of torsion. All cases
      with evidence of torsion were managed surgically post partum, and in all patients
      this complication was confirmed. The remaining nine cases were followed up by
      repeated ultrasonograms, and in all patients disappearance of the cyst was
      documented within the first 6 months of life. The mean size of cysts with
      evidence of torsion was 5.41 +/- 0.25 cm, and the mean size of those without
      torsion was 4.33 +/- 0.3 cm (p less than 0.01). Histologic examination of the
      surgical specimen in the cases with evidence of torsion revealed follicular cysts
      in three cases and necrotic ovarian cysts with no specific epithelial findings in
      the remaining three. We recommend continuous ultrasonographic assessment of
      antenatally diagnosed cysts and believe that the choice of treatment depends on
      the appearance of the cyst and its evolution throughout pregnancy.

PMID- 2003555
TI  - Position change and central hemodynamic profile during normal third-trimester
      pregnancy and post partum.
AB  - Central hemodynamic response to position change was assessed in 10 normotensive
      primiparous patients between 36 and 38 weeks' gestation. Studies were repeated
      between 11 and 13 weeks post partum. Compared with the left lateral position, we
      observed a mean 9% fall in cardiac output in the supine position and an 18% fall
      when patients were standing. When standing, these patients had a 30% increase in
      pulse and a 21% fall in left ventricular stroke work index. The orthostatic
      response after pregnancy was much more labile than that during the third
      trimester. These findings have important descriptive implications for the
      understanding of the human response to orthostasis during pregnancy, as well as
      clinical implications for patients at risk of uteroplacental insufficiency and
      for working women during pregnancy.

PMID- 2003556
TI  - Serum levels of inhibin in maternal and umbilical blood during pregnancy.
AB  - Inhibin levels were measured by a double antibody heterologous radioimmunoassay
      in the peripheral serum of 75 pregnant women throughout gestation and in serum
      from the umbilical vein and artery, which was obtained at the time of delivery.
      For reference, samples were obtained from 20 nonpregnant women in the early (days
      0 to 3), mid (days 4 to 8), and late (days 9 to 14) luteal or follicular phase.
      Maternal serum levels of inhibin (mean +/- SEM) in early (6 to 12 weeks)
      gestation (36.4 +/- 2.6 U/ml, n = 36) were significantly (p less than 0.01)
      higher than those in serum from nonpregnant women in the mid (23.9 +/- 2.5 U/ml,
      n = 19) or late (11.3 +/- 0.6 U/ml, n = 19) luteal phase. Inhibin levels in
      maternal serum fell to 15.9 +/- 1.4 U/ml (n = 24) in mid (14 to 20 weeks)
      gestation and then gradually increased during late (21 to 40 weeks) gestation to
      peak levels of 49.4 +/- 5.1 U/ml (n = 9) at 36 to 37 weeks. Inhibin levels
      declined in parallel with human chorionic gonadotropin concentrations during the
      first trimester (r = 0.587 at p less than 0.01). Significant positive
      correlations (p less than 0.001) were observed between serum levels of inhibin
      and 17 beta-estradiol (r = 0.560), progesterone (r = 0.648), and human placental
      lactogen (r = 0.715) during mid and late (20 to 40 weeks) gestation. Inhibin
      levels in umbilical vein serum (38.5 +/- 1.3 U/ml, n = 5) were not different from
      those in umbilical artery serum (39.4 +/- 3.6 U/ml) but were significantly (p
      less than 0.01) lower than those in maternal serum (50.9 +/- 5.3 U/ml), which was
      obtained at the time of delivery. By day 5 of puerperium, serum levels of inhibin
      in the maternal vein were extremely low (2.3 +/- 0.1 U/ml, n = 7); these levels
      were nearly one fifth lower than follicular phase levels of 10.9 +/- 3.4 U/ml (n
      = 38). We propose that maternal inhibin in early gestation is secreted from the
      corpus luteum of pregnancy but that increasing inhibin levels during mid and late
      gestation result from inhibin that is produced by the placenta. The lack of an
      umbilical arterial-venous gradient for inhibin and the higher levels of inhibin
      in maternal serum argue against a fetal source of inhibin in the maternal
      circulation. The physiologic function of inhibin that is produced by the corpus
      luteum and by the placenta remains to be determined.

PMID- 2003557
TI  - Transplacental, amniotic, urinary, and fetal fluid dynamics during very-large
      volume fetal intravenous infusions.
AB  - With rapid intravenous infusion of very large volumes of isotonic saline
      solutions into the fetus, the fluid could stay within the fetal body, thereby
      creating hydrops fetalis, be transferred into the amniotic fluid through the
      fetal kidneys, thereby creating polyhydramnios, or be transferred across the
      placenta into the maternal circulation. This study was designed to explore these
      possibilities. After a 1-hour control period, 10 near-term chronically
      catheterized ovine fetuses were infused intravenously with 4 L (greater than 100%
      of fetal weight) of either isotonic saline solution or lactated Ringer's solution
      over 4 hours. Fetal arterial pressure was significantly elevated by 7 mm Hg
      throughout the infusion (p less than 0.00001). Venous pressure underwent a
      transient rise (4.8 mm Hg) at 20 minutes of infusion and remained elevated (2.7
      mm Hg) during the rest of the infusion (p less than 0.00001). Fetal urine flow
      increased by an average of 5.7 +/- 0.4 ml/min throughout the infusion (p less
      than 0.00001) and accounted for 34.1% +/- 2.6% of the infused volume. Estimated
      fetal extracellular fluid volume increased by 17.7% +/- 1.8% of the infused
      volume. Because fetal fluid retention, urine flow, and amniotic fluid volume
      changes accounted for only half of the infused fluid, the remainder of the
      infused volume must have crossed the placenta and entered the maternal
      circulation. Given the above changes in vascular pressures, this requires a
      filtration coefficient of the placenta 50 to 100 times the previously reported
      values. Thus we conclude that relatively small changes in fetal vascular
      pressures dramatically alter the filtration capacity of the ovine placenta and
      transplacental volume flow.

PMID- 2003558
TI  - Enhancement of germ tube formation in Candida albicans by beta-endorphin.
AB  - Candida albicans is a dimorphic yeast that causes vaginal infections after its
      transition from a budding yeast to a germinating hyphal form. We report here that
      physiologic concentrations of beta-endorphin, a neuropeptide with
      immunomodulating activity produced during stress or physical exercise, stimulates
      germ tube formation in C. albicans. The percent of germination was proportional
      to the endorphin concentration, over the 5 x 10(-12) to 5 x 10(-10) mol/L range
      tested. beta-Endorphin modified by removal of the 4-carboxy-terminal amino acids
      and (D-Ala2)-beta-endorphin, a peptide with a protease-resistant amino terminal
      end, were equally effective in stimulating germination. In contrast, N-acetylated
      beta-endorphin did not stimulate germination. Antisera to beta-endorphin also
      completely blocked beta-endorphin-stimulated germ tube formation. Two clinical
      isolates of C. albicans were also responsive to beta-endorphin. Stimulation of
      germ tube formation by beta-endorphin occurred only in sera from ovulating women.
      Germination in sera from women using oral contraceptives, in sera from men, or in
      glucose beef extract broth was not influenced by beta-endorphin. Thus C. albicans
      may be able to recognize and respond to neuroendocrine signals in ovulating
      women.

PMID- 2003559
TI  - The effect of volume expansion on placental blood flow in awake hypovolemic rats
      in late pregnancy.
AB  - Symptomatic hypovolemia in preeclampsia is often treated by volume expansion.
      However, the effect of this treatment on placental blood flow is unclear. In the
      present study the hypothesis was tested that slow volume expansion, imposed on
      volume-depleted rats, does not compromise placental blood flow. Mild hypovolemia
      was induced in rats in late pregnancy by 24 hours' thirsting. The resulting
      gradual dehydration was associated with a 7% reduction in blood volume. These
      rats were then subjected to blood volume expansion by a continuous infusion with
      a plasma substitute. Volume expansion increased blood volume by 32% and cardiac
      output by 73%. The extra cardiac output was distributed to kidneys, carcass, and
      portal bed. Placental blood flow decreased by 31%. The pattern of response was
      comparable to the one previously observed in normovolemic rats. However, the
      magnitude of the changes was larger, probably associated with a delayed or
      impaired diuretic response. These data suggest that volume expansion therapy in
      mildly hypovolemic pregnant rats elicits an exaggerated hemodynamic response as
      compared with normovolemic rats, including placental compromise.

PMID- 2003560
TI  - Pharmacokinetics of pentamidine in Sprague-Dawley rats in late pregnancy.
AB  - To our knowledge, placental transfer of pentamidine has not been previously
      studied in vivo. In the present study, the pharmacokinetics of pentamidine were
      analyzed in late gestation (18 days) among Sprague-Dawley rats. Pentamidine's
      kinetics were assessed in the following maternal compartments over a 12-hour
      period in 16 timed-pregnant rats: serum, liver, and kidney. Placentas were also
      analyzed for pentamidine concentration as were fetal brain, liver, and kidney
      tissues. Significant placental transfer of the drug was found, with pentamidine
      reaching all fetal compartments studied. Notably, by the twelfth hour fetal brain
      tissue achieved pentamidine concentrations that were not significantly different
      from those of maternal serum at the second hour of the experiment. This is an
      interesting observation because adult mouse and rat brains were found to be
      unexposed to the drug.

PMID- 2003561
TI  - Thumbtacks.

PMID- 2003562
TI  - The importance of the postcoital test.

PMID- 2003563
TI  - First-trimester transvaginal ultrasonographic screening: incidence of structural
      anomalies.

PMID- 2003564
TI  - Metabolic effects of danazol.

PMID- 2003565
TI  - Fetal subdural hematoma before labor.

PMID- 2003566
TI  - Unraveling the mysteries of vulval ulceration in human immunodeficiency virus
      seropositive women.

PMID- 2003567
TI  - Pelvic muscles and episiotomy.

PMID- 2003568
TI  - Response of isolated adult canine cardiac myocytes to prolonged hypoxia and
      reoxygenation.
AB  - Isolated adult canine ventricular myocytes incubated in the absence of glucose
      with the respiratory inhibitor rotenone retained 67% of ATP (control, 26.0 +/-
      0.9 nmol/mg protein) during 3-h incubation, yet phosphocreatine fell to 23% of
      initial content. Lactate production proceeded at a constant rate of 5 nmol.mg
      1.min-1 in rotenone-treated glucose-free myocytes. A 36% decline in rod-shaped
      cells and an increase in percent 22Na permeation from 37% in aerobic cells
      (approximately 13 mM intracellular sodium) to 68% in rotenone-treated glucose
      free myocytes paralleled the loss of ATP. Total exchangeable calcium was
      maintained at control aerobic levels. Exposure of canine cells to 3-h hypoxia in
      the absence of glucose followed by 5-min reoxygenation resulted in a 73% decrease
      in ATP, a rise in calcium from 3.3 +/- 0.2 to 6.6 +/- 1.6 nmol/mg, and an
      increase in 22Na permeation to 111%. Under these conditions the number of rod
      shaped myocytes declined by 77%, with corresponding increases in viable
      contracted and hypercontracted myocytes. The response of canine myocytes to
      severe hypoxia and reaeration contrasts greatly to earlier studies using adult
      rat cardiac myocytes [see Hohl et al. Am. J. Physiol. 242 (Heart Circ. Physiol.
      11): H1022-H1030, 1982]. Species differences with respect to basal metabolism,
      rates of ATP production and degradation, and regulation of cation movements are
      most likely responsible for the observed differences.

PMID- 2003569
TI  - Perpetuation of muscle fibers after removal of stretch in the Japanese quail.
AB  - Stretch-overload has been shown to increase muscle mass in the anterior
      latissimus dorsi (ALD) of the adult quail by increasing both fiber size and
      number, but it is not known whether the new muscle fibers or fiber size is
      maintained after removal of the stretch stimulus. A weight was added to the right
      wing of 40 adult quail while the left wing in each bird served as an intra-animal
      control. The weight was removed after 30 days of stretch, and terminal
      experiments were conducted 0, 30, 60, or 90 days thereafter. Average slow beta
      fiber area increased by 53.4 +/- 17.5% (SE) after 30 days of stretch, but it was
      not different from control area by 30 days poststretch removal. Total fiber
      number was determined after nitric acid digestion of connective tissue. It
      increased by 41.3 +/- 2.3% after 30 days of stretch, but it was 28.5 +/- 5.2%
      greater than control after unweighting for 30-90 days. Thus, once the overload
      was removed, fiber number returned to control levels more slowly than fiber mass
      or volume. The data suggest that mechanisms that downregulate fiber number and
      fiber size may differ in the ALD of the Japanese quail.

PMID- 2003570
TI  - Lysophosphatidylcholine and sodium-calcium exchange in cardiac sarcolemma:
      comparison with ischemia.
AB  - Lysophosphoglyceride accumulation in ischemic myocardium has been hypothesized to
      be a mechanism for altered sarcolemmal properties that underlie
      electrophysiological changes and Ca2+ accumulation in ischemia. We find that in
      vitro application of lysophosphatidylcholine to normal canine sarcolemmal
      vesicles at a concentration of 0.3 mumol/mg sarcolemmal protein inhibits Na(+)
      Ca2+ exchange. Both maximum velocity (Vmax) for Ca2+ transport and Ca2+ affinity
      are reduced by lysophosphatidylcholine, whereas in ischemia only Vmax is reduced
      [M. M. Bersohn, K. D. Philipson, and J. Y. Fukushima. Am. J. Physiol. 242 (Cell
      Physiol. 11): C288-C295, 1982]. This amount of lysophosphatidylcholine does not
      affect sarcolemmal passive permeability to either Ca2+ or Na+. Treatment of
      sarcolemma with phospholipase A2 sufficient to inhibit Na(+)-Ca2+ exchange
      velocity by 50% causes large increases in sarcolemmal lysophosphatidylcholine and
      lysophosphatidylethanolamine. On the other hand, 1 h of ischemia in rabbit hearts
      does not affect sarcolemmal phospholipid composition. Thus, although in vitro
      treatment with lysophosphatidylcholine or phospholipase A2 has profound effects
      on sarcolemmal properties, sarcolemmal accumulation of lysophosphatidylcholine
      cannot account for the effects of ischemia as measured in highly purified
      sarcolemmal vesicles from ischemic hearts.

PMID- 2003571
TI  - Uncoupling of cardiac cells by fatty acids: structure-activity relationships.
AB  - The permeability and conductance of gap junctions between pairs of neonatal rat
      heart cells were rapidly and reversibly decreased by oleic acid in a dose- and
      time-dependent manner. Other unsaturated fatty acids (C-18: cis 6, 9, or 11, and
      C-18, 16, and 14, cis 9), saturated fatty acids (C-10, 12, and 14), and saturated
      fatty alcohols (C-8, 10, and 12) also caused uncoupling. The most effective
      compounds of the unsaturated and saturated fatty acid and saturated fatty alcohol
      series caused essentially complete uncoupling at comparable aqueous
      concentrations. However, oleic acid uncoupled cells at membrane concentrations as
      low as 1 mol%, whereas decanoic acid required upwards of 35 mol%. The channels
      that support the action potential remained functional at these same membrane
      concentrations. The data are discussed in terms of the possible mechanism by
      which these compounds cause uncoupling and the possible role of uncoupling by
      nonesterified free fatty acids in the initiation of arrhythmias during and after
      ischemic insults.

PMID- 2003572
TI  - Unusual [Ca2+] dependence of vascular smooth muscle cell shortening velocity.
AB  - The relationship between unloaded shortening velocity and Ca2+ concentration was
      determined for hog carotid arterial smooth muscle cells, freshly isolated by
      digestion with papain. Cells were exposed to various [Ca2+] for 60 s at 37
      degrees C and then stimulated with 10 microM histamine. Cell length was measured
      by a video analysis system. Shortening velocity was expressed as an exponential
      rate constant by fitting the cell lengths to the following equation: length =
      Lmin + (Lmax-Lmin)exp[-v (time-latency)], where Lmax is length before
      contraction, Lmin is shortest length reached, time is time elapsed after addition
      of agonist, latency is time from addition of agonist until contraction starts,
      and v is the exponential rate constant (s-1). Cells shortened substantially,
      usually reaching one-fourth to one-third of their initial length within 1 min.
      Shortening velocities of the cells were much faster than published values of
      maximum shortening velocity in muscle strips from this same tissue. At 1.6 mM
      Ca2+, v was 0.173 +/- 0.015 s-1. When Ca2+ was increased to 5 or 10 mM, v was not
      significantly different. However, when Ca2+ was decreased to 0.5 and 0.16 mM, v
      increased to 0.288 and 0.258 s-1, respectively. The difference between 0.5 and
      1.6 mM was significant. The unexpected increase in shortening velocity at low
      Ca2+ was also seen when 10 mM caffeine was used as a stimulus: v at 1.6 mM Ca2+
      was 0.156 s-1, whereas v at 0.16 mM Ca2+ was 0.272 s-1. The high shortening
      velocities we measured suggest that measurements made on multicellular tissues
      seriously underestimate the potential shortening velocity of isolated individual
      cells.

PMID- 2003573
TI  - Kinetic analysis of receptor-mediated endocytosis of epidermal growth factor by
      isolated rat hepatocytes.
AB  - The interaction of epidermal growth factor (EGF) with cell surface receptors and
      their subsequent endocytosis in isolated rat hepatocytes were analyzed by
      measuring changes in the concentrations of cell surface-bound, internalized, and
      degraded EGF. The kinetic model proposed by Wiley and Cunningham (Cell 25: 433
      440, 1981) and Gex-Fabry and Delisi [Am. J. Physiol. 247 (Regulatory Integrative
      Comp. Physiol. 16): R768-R779, 1984] was basically utilized for the model
      analysis. The following kinetic parameters were obtained: association and
      dissociation rate constants for EGF-receptor interaction, internalization rate
      constant for EGF-receptor complex (kappa e), internalization rate constant for
      free receptor (kappa t), sequestration rate constant (kappa s) of the complex
      from shallow (exchangeable) to deep (nonexchangeable) membraneous compartment,
      intracellular degradation rate constant and initial cell-surface receptor
      density. The kappa s value, which was obtained by analyzing the time profiles of
      EGF association with cells, was approximately 5-10 times larger than the kappa e
      value determined by directly measuring internalized EGF with the acid-washing
      technique. This suggests the necessary presence of deep (nonexchanging)
      compartment of the complex in the plasma membrane. The calculated kappa e value
      is at least several times larger than the kappa t value, yielding the kinetic
      basis for the occurrence of receptor downregulation induced by excess EGF. We
      conclude that, in the overall receptor-mediated processing of EGF after bound to
      the cell surface receptors, the dissociation process is rapid [half-time (t1/2)
      less than 1 min], the degradation process is much slower (t1/2 approximately
      equal to 3 h), and the receptor internalization process is intermediate (t1/2
      approximately equal to 6-7 min). In addition, two pools for EGF-receptor complex
      in the plasma membrane seem to be present, although their identification cannot
      be made.

PMID- 2003574
TI  - Insulin and IGF-I induce pronounced hypertrophy of skeletal myofibers in tissue
      culture.
AB  - Skeletal myofibers differentiated from primary avian myoblasts in tissue culture
      can be maintained in positive nitrogen balance in a defined serum-free medium for
      at least 6-7 days when embedded in a three-dimensional collagen gel matrix.
      Incubation of established myofiber cultures for 3-7 days with insulin (1 microM)
      or insulin-like growth factor I (IGF-I, 32 nM) stimulates both cell hyperplasia
      and myofiber hypertrophy. Mean myofiber diameter increases 71-98%. Insulin-like
      growth factor II stimulates cell hyperplasia but not myofiber hypertrophy. Cell
      growth results from a 42-62% increase in total protein synthesis and a 28-38%
      decrease in protein degradation. Myosin heavy-chain content increases 183-258%
      because of a 55% stimulation of myosin synthesis and 33-61% inhibition of
      degradation. Associated with myofiber hypertrophy is a 87-148% increase in the
      number of myofiber nuclei per unit myofiber length. The results indicate that
      insulin and IGF-I, but not IGF-II, can induce rapid myofiber hypertrophy in
      vitro, most likely by stimulating myoblast proliferation and/or fusion to
      established myofibers.

PMID- 2003575
TI  - Mitogenic signals for platelet-derived growth factor isoforms in liver fat
      storing cells.
AB  - Platelet-derived growth factor (PDGF), a key mitogen for liver fat-storing cells
      (FSC), is a dimeric molecule that occurs as homodimers or heterodimers of related
      polypeptide chains (PDGF-BB, -AB, and -AA). In chronic inflammation of the liver
      lobule, any of the three dimeric forms of PDGF derived from multiple sources
      could potentially interact with FSC. We explored the effects of the three
      different PDGF isoforms on DNA synthesis and early signal transduction pathways
      potentially related to PDGF mitogenicity in rat liver FSC. PDGF-BB homodimer and 
      AB heterodimer induced a marked increase in DNA synthesis, whereas the effect of
      PDGF-AA homodimer was considerably lower. Moreover, the mitogenicity of each
      isoform proportionally correlated with their effects on phosphoinositide turnover
      and intracellular Ca2+. Both the PDGF-BB and -AB dimers likely interact with the
      PDGF-beta-receptor, although PDGF-AB requires at least one alpha-receptor. The
      low responsiveness to PDGF-AA could not be accounted for by downregulation of the
      PDGF-alpha-receptor because FSC expressed very low levels of PDGF-A- and B-chain
      mRNAs and did not secrete detectable amounts of PDGF activity in the conditioned
      media. In addition, preincubation of FSC with suramin, a potent inhibitor of PDGF
      binding to its receptor, failed to increase PDGF-AA-induced DNA synthesis. These
      results are consistent with a predominant expression of PDGF-beta-receptor in
      liver FSC, that is linked to phospholipase C activation.

PMID- 2003576
TI  - Foreign anions modulate volume set point of sheep erythrocyte K-Cl cotransport.
AB  - Preequilibration at 37 degrees C in isosmotic media with Cl replaced by lyotropic
      (foreign) anions reversibly increased Cl-dependent K efflux and Rb influx, the
      inhibition by furosemide, and thus K-Cl cotransport in low-K but not in high-K
      sheep erythrocytes with the following order of effectiveness: SCN greater than I
      greater than NO3 greater than Cl = Br. This effect depended on time, temperature,
      and anion concentration and was reversible. Preincubation in isosmotic SCN at 37
      degrees C stimulated K-Cl flux in anisosmotic Cl media (370-240 mosM) by
      increasing the volume sensitivity through shifting the point of zero K-Cl flux by
      approximately 100 mosmol. Thus even shrunken cells exhibited K-Cl cotransport.
      Preincubation in hyperosmotic SCN or Cl (440 mosM) followed by K flux in
      hyposmotic Cl (240 mosM) caused a 30-min lag phase that was absent when cells
      were swollen only. Hence, foreign anions increased the K flux rate in Cl,
      suggesting upregulation of K-Cl cotransport through new sites or higher turnover
      per transporter. The anions must act directly on proteins and/or lipids as the
      accompanying intracellular pH (pHi) changes were too small to attribute the K-Cl
      flux activation to cellular acidification. After thiol alkylation, which also
      activates K-Cl cotransport, SCN preexposure at 37 degrees C became ineffective.
      Carbethoxylation significantly reduced the foreign anion enhancement of K-Cl
      cotransport and abolished K efflux in Br. It is concluded that interaction of
      anions through carbethoxylation-sensitive sites with thiols may determine the
      level of K-Cl cotransport activity.

PMID- 2003577
TI  - Role of cytosolic Ca in renal tubule damage induced by anoxia.
AB  - Cytosolic free Ca (Caf) was measured in three different preparations of freshly
      prepared proximal tubules from the rabbit kidney during energy deprivation using
      fura-2. Isolated perfused tubules, tubules immobilized on glass cover slips, and
      tubules in suspension were subjected to inhibitors of oxidative phosphorylation
      ("chemical hypoxia"); the latter two preparations were also subjected to 40 min
      of anoxia. During normoxia, Caf ranged from 100 to 180 nM in all three
      preparations, and chemical hypoxia caused either no change or a small (30-100%)
      increase in Caf values. Subsequent addition of Ca ionophores increased Caf to 300
      500 nM in the first 2 min and to greater than 1 microM after 15 min. In
      individual experiments, anoxia produced similar responses to those of chemical
      hypoxia, eliciting no average significant change in Caf, despite clear evidence
      for impaired respiration and plasma membrane damage after 40 min of anoxia. This
      lack of change in Caf was unrelated to "Ca buffering" by fura-2 or inactivation
      of the dye, since Caf increased to 666 +/- 59 nM upon addition of Ca ionophore
      during anoxia. These data suggest that increased Caf is not a prerequisite for
      cellular damage during anoxia in proximal renal tubules. Furthermore, no apparent
      alteration in plasma membrane permeability to Ca occurs before membrane
      disruption. Decreased ATP seems to initiate a series of Caf-independent events
      that cause irreversible injury.

PMID- 2003578
TI  - Calcium stimulates glucose transport in skeletal muscle by a pathway independent
      of contraction.
AB  - In this study we investigated the possibility that an increase in cytoplasmic
      Ca2+ concentration that is too low to cause muscle contraction can induce an
      increase in glucose transport activity in skeletal muscle. The compound N-(6
      aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), which induces Ca2+ release
      from the sarcoplasmic reticulum (SR), caused a dose-dependent increase in tension
      in rat epitrochlearis muscles at concentrations more than approximately 200
      microM. Although 100 microM W-7 did not increase muscle tension, it accelerated
      loss of preloaded 45Ca2+. Glucose transport activity, measured with the
      nonmetabolizable glucose analogue 3-O-methylglucose, increased sixfold in muscles
      treated for 100 min with 50 microM W-7 (P less than 0.001) and eightfold in
      response to 100 microM W-7 (P less than 0.001). The increase in glucose transport
      activity was completely blocked with 25 microM cytochalasin B. There was no
      decrease in ATP or creatine phosphate concentrations ([approximately P]) in
      muscles incubated with 50 microM W-7. Dantrolene (25 microM), which blocks Ca2+
      release from the SR, blocked the effects of W-7 both on 45Ca2+ release and on
      glucose transport activity. 9-Aminoacridine, another inhibitor of Ca2+ release
      from the SR, also blocked the stimulation of hexose transport by W-7. Caffeine, a
      compound structurally unrelated to W-7 that also releases Ca2+ from the SR, also
      increased glucose transport activity. Incubation of muscles with 3 mM caffeine
      for 30 min, which did not cause contraction or lower [approximately P], induced a
      threefold increase in 3-O-methylglucose transport (P less than 0.001). These
      results provide evidence suggesting that an increase in cytoplasmic Ca2+ too low
      to cause contraction or [approximately P] depletion can bring about an increase
      in glucose transport activity in skeletal muscle.

PMID- 2003579
TI  - Differential sorting of two glucose transporters expressed in insulin-sensitive
      cells.
AB  - The insulin-regulatable glucose transporter (IRGT) is specifically expressed in
      muscle and fat cells and undergoes translocation from an intracellular
      compartment to the cell surface following acute insulin treatment. This study
      examined sorting differences between the IRGT and the homologous
      HepG2/erythrocyte/brain glucose transporter (HepG2 GT) when expressed together in
      insulin-responsive 3T3-L1 adipocytes. The ratio of the amount of transporter per
      unit protein in the plasma membrane fraction vs. the intracellular membrane
      fraction was 1:2 for the HepG2 GT and 1:30 for the IRGT. Insulin treatment
      increased the plasma membrane concentration of the IRGT by 10-fold and the HepG2
      GT by 3.5-fold. This distribution was confirmed by confocal immunofluorescence
      microscopy. Differential sorting within intracellular organelles was evident by
      sucrose gradient analysis and immunoisolation of transporter vesicles and by
      double immunofluorescence labeling. We propose that differential sorting at an
      intracellular locus preferably withdraws the IRGT from a pathway which is in
      close communication with the plasma membrane, thus allowing the IRGT to regulate
      glucose entry into fat and muscle cells in a highly insulin-regulated fashion.

PMID- 2003580
TI  - Ethylisopropylamiloride-sensitive pH control mechanisms modulate vascular smooth
      muscle cell growth.
AB  - The reported effects of alterations in Na-H exchange activity on mitogenesis are
      variable and appear dependent on the cell type examined. We examined the effects
      of reductions in ethylisopropylamiloride (EIPA)-sensitive pH-regulating
      mechanisms including Na-H exchange and alterations in intracellular pH (pHi) on
      the growth characteristics of rat aortic smooth muscle cells (RASM) cultured in
      serum-containing bicarbonate-buffered medium. Exposure of RASM replicating in
      bicarbonate-containing medium to the Na-H exchange inhibitors EIPA,
      dimethylamiloride (DMA), or amiloride (A) attenuated their replication rate. The
      order of potency of the inhibitors (EIPA greater than DMA much greater than A)
      was similar to their documented effects on Na-H exchange activity and to their
      order of potency for inhibiting recovery from CO2-induced acidosis in these
      cells. Reductions in pHi induced by lowering extracellular pH also attenuated the
      incorporation of [3H]-thymidine into DNA, while increases in pHi were associated
      with an acceleration in the rate of incorporation of [3H]thymidine into DNA. The
      effects of the Na-H exchange inhibitors on RASM replication were due to a
      reduction in the ability of the smooth muscle cells to enter the S phase of the
      mitotic cell cycle. This appeared predominantly the consequence of effects late
      within the G1 phase of the cell cycle. Concentrations of EIPA that markedly
      reduced the ability of RASM to enter S phase and to replicate also attenuated the
      increase in protein synthesis occurring 6-8 h after exposure to serum.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 2003581
TI  - Cholinergic stimulation produces oscillations of cytosolic Ca2+ in a secretory
      epithelial cell line, T84.
AB  - The effects of carbamylcholine (carbachol) on intracellular Ca2+ concentration
      ([Ca2+]c) of T84 cells were examined using the fluorescent Ca2+ indicator fura-2
      and microfluorometric techniques. In single isolated cells, carbachol (100
      microM) caused a rapid increase in [Ca2+]c of 184 +/- 15 nM (SE, n = 44) from a
      resting value of 56 +/- 7 nM. This initial transient was followed by a series of
      oscillations in 68% of the cells. Atropine (10 microM) blocked this response.
      Removal of bath Ca2+ did not inhibit the rise in [Ca2+]c or oscillations, but the
      response duration was shortened in 47% of the cells. The amplitude and latency of
      the initial Ca2+ rise, frequency of oscillations, and number of responding cells
      varied with the agonist concentration. We have previously shown that carbachol
      induces an oscillating K+ conductance in T84 cells [D. Devor, S. Simasko, and M.
      Duffey. Am. J. Physiol. 258 (Cell Physiol. 27): C318-C326, 1990]. Simultaneous
      measurement of membrane K+ current and fura-2 fluorescence in the same cell
      demonstrated a correlation between the rise in [Ca2+]c and increase in K+
      current. These results show that a rise in [Ca2+]c and oscillations is likely to
      underlie the membrane K+ current responses to carbachol in T84 cells. Responses
      from a single cell within a subconfluent monolayer were different from those of
      isolated cells. In cells of a monolayer the initial [Ca2+]c rise (111 +/- 8 nM; n
      = 41) was followed by a decline to a stable plateau, and oscillations were not
      seen. Removal of bath Ca2+ both reduced the initial transient and eliminated the
      plateau phase of the response. These results suggest that cell-to-cell contact or
      differentiation during monolayer formation influences the Ca2+ handling
      mechanisms of T84 cells.

PMID- 2003582
TI  - Length-dependent activation by Ba2+ and Sr2+ of skinned cardiac and skeletal
      muscle of the rabbit.
AB  - Over a wide range of sarcomere lengths, force activation by Ca2+, Ba2+, and Sr2+
      was studied in papillary muscle and in fast skeletal fibers of the gracilis
      muscle of the rabbit, both skinned by means of freeze drying. The length-tension
      relations of Ba2+ activation differ significantly from those of Sr2+ and Ca2+
      activation with respect to both the value and the position of the maximum. At
      (almost) full activation, force induced in gracilis muscle by Ba2+ was 50% of the
      developed force induced by Ca2+. The position of the Sr2+ sensitivity curve for
      papillary muscle preparations is independent of sarcomere length, in contrast to
      the position of the Ca2+ sensitivity curves. The binding of Sr2+ to the papillary
      preparation proves to be very stable as observed from the long-lasting relaxation
      after activation. Immersion of the papillary preparation in the relaxation fluid
      after activation with Ba2+ results in a tension transient: a rise in tension
      followed by a decrease was observed. The maximal value of the tension transient
      was up to twice the steady tension, dependent on Ba2+ concentration. The steady
      state tension was approximately 50% of the Ca2(+)-induced tension. Ba2+
      sensitivity curves are not sigmoidal but show a maximum. Above [Ba2+] greater
      than 10(-5) to 10(-4) M (dependent on sarcomere length) tension decreased. These
      observations suggest that two counteracting processes govern Ba2+ contraction in
      papillary muscle preparations, namely activation and inhibition.

PMID- 2003583
TI  - K(+)-H+ exchange, a fundamental cell acidifier in corneal epithelium.
AB  - Rabbit corneal epithelial cells, loaded with the pH-sensitive fluorescent dye
      2',7'-bis(2-carboxy-ethyl)-5(6)-carboxyfluorescein, show a profound acidification
      (pH 7.33 to 6.75) in HCO3(-)-free Ringer solution when exposed to the Na(+)-H+
      exchange inhibitor amiloride. This indicates that the cells are under a constant
      acid load that is being countered by Na(+)-H+ exchange. Amiloride-induced
      acidification was affected neither by incubation in Cl(-)-free Ringer solution
      nor by hypoxia, indicating that the potential acid loaders, Cl(-)-HCO3- (or OH-)
      exchange or glycolytic metabolism, are not contributing to the acidification. The
      possibility of a H+ influx dependent on the outward K+ gradient was tested.
      Perfusion with a high-K+ Ringer solution (77 mM) caused Na(+)- and Cl(-)
      independent alkalinizations. Membrane depolarization by gramicidin, Ba2+, Cl(-)
      free Ringer solution, or ouabain all produced small (less than 0.1 pH units)
      acidifications, inconsistent with contribution by a membrane potential driven
      passive H+ influx. In Na(+)-free Ringer solution, intracellular pH (pHi) of 6.4
      6.6, addition of nigericin (a 1K(+)-1H+ ionophore) produced no significant change
      in pHi, indicating that [K+]i/[K+]o = [H+]i/[H+]o. Both amiloride-induced
      acidifications and high-K(+)-induced alkalinizations were significantly
      stimulated by the presence of 1 mM ZnSO4 and unaffected by H2-DIDS (0.5 mM, an
      anion transport blocker) or 100 microM SCH28080 (K(+)-H(+)-ATPase blocker). In
      the absence of a demonstrable H+ conductance, it is concluded that amiloride
      induced acidification and K(+)-induced pHi changes are via a carrier-mediated
      K(+)-H+ exchanger. In addition to pHi regulation, K(+)-H+ exchange may play a
      role in cell volume control.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2003584
TI  - Intermediary metabolism and its relationship with ion transport in isolated
      guinea pig colonic epithelial cells.
AB  - We describe a method to isolate surface cells from guinea pig distal colon that
      obtains a good yield and high viability, as demonstrated by a 99% exclusion of
      trypan blue, only a 10% liberation of lactate dehydrogenase after 30-min
      incubation at 37 degrees C, and the inability of succinate to stimulate oxygen
      consumption before plasma membrane permeabilization. Oxygen consumption (QO2)
      measured after the sequential addition of the following drugs showed that
      oligomycin inhibited QO2 by 67%, carbonyl cyanide p
      trifluoromethoxyphenylhydrazone increased QO2 by approximately 70% of the basal
      consumption, and rotenone inhibited QO2 by 90%. Cells at 37 degrees C for 30 min
      maintained intracellular Na+ and K+ concentrations of 25 and 120 mM,
      respectively. The ATP consumed by the Na(+)-K+ pump was derived from oxidative
      phosphorylation (79%) and from glycolysis (21%). Initial rates for Na+ and K+
      transported by the pump were 105 +/- 10 and 65 +/- 5 nmol.mg protein-1.min-1,
      respectively. The rates of Na+ and K+ transported per ATP consumed were estimated
      to be 2.5 Na+/ATP and 1.6 K+/ATP.

PMID- 2003586
TI  - Direct measurement of intracellular pressure.
AB  - The feasibility of using the servo-null technique for direct measurement of
      intracellular pressure (Pin) was investigated. A large cell, the Xenopus laevis
      oocyte, was chosen for study, and it was established that Pin obtained with this
      method was both stable and accurate in these cells. Median resting Pin in oocytes
      was found to be 0.27 cmH2O, range 0.14-0.61 cmH2O. During osmotic swelling Pin
      increased, in a non-linear fashion, to a value of 4.11 cmH2O, range 2.61-8.91
      cmH2O, with increases in cell volume (Vc) of 24 +/- 3% (SE). This technique may
      be of use in the study of cellular mechanics.

PMID- 2003585
TI  - Skeletal muscle bioenergetics during frequency-dependent fatigue.
AB  - The bioenergetic correlates of skeletal muscle fatigue were assessed in vivo with
      phosphorus-31 nuclear magnetic resonance (31P-NMR) spectroscopy. After surgical
      construction of latissimus dorsi muscle ventricles, seven beagles underwent 31P
      NMR spectroscopy during 12-min exercise protocols at 25- and 85-Hz stimulation
      frequencies and during both isovolumetric and dynamic contractions. Exercise at
      85 Hz was associated with significantly greater fatigue than exercise at 25 Hz.
      At both frequencies, the onset of exercise was associated with a marked increase
      in inorganic phosphate (Pi) and a decrease in phosphocreatine (PCr). As the
      muscle fatigued at 85 Hz but not at 25 Hz, the phosphorus spectra returned to
      near baseline with a decrease in Pi and increase in PCr. For a given amount of
      force generated, the Pi-to-PCr ratio was higher for dynamic contractions than for
      isovolumetric contractions. This study indicates that high-frequency fatigue is
      unlikely to result from the direct effects of high-energy phosphate metabolism
      and that contractions producing external work consume more metabolic energy than
      equally forceful isometric contractions.

PMID- 2003587
TI  - Effect of baroreceptor denervation on stimulation of drinking by angiotensin II
      in conscious dogs.
AB  - Angiotensin II causes marked stimulation of drinking when it is injected
      centrally but is a relatively weak dipsogen when administered intravenously.
      However, it has been proposed that the dipsogenic action of systemically
      administered angiotensin II may be counteracted by the pressor action of the
      peptide. To test this hypothesis, the dipsogenic action of angiotensin II was
      investigated in dogs, in which low and high baroreceptor influences had been
      eliminated by denervation of the carotid sinus, aortic arch, and heart. In five
      sham-operated dogs, infusion of angiotensin II at 10 and 20 ng.kg-1.min-1
      increased plasma angiotensin II concentration to 109.2 +/- 6.9 and 219.2 +/- 38.5
      pg/ml and mean arterial pressure by 20 and 29 mmHg, respectively, but did not
      induce drinking. In four baroreceptor-denervated dogs, the angiotensin II
      infusions produced similar increases in plasma angiotensin II concentration and
      mean arterial pressure but, in contrast to the results in the sham-operated dogs,
      produced a dose-related stimulation of drinking. Water intake with the low and
      high doses of angiotensin II was 111 +/- 44 and 255 +/- 36 ml, respectively. The
      drinking responses to an increase in plasma osmolality produced by infusion of
      hypertonic sodium chloride were not different in the sham-operated and
      baroreceptor-denervated dogs. These results demonstrate that baroreceptor
      denervation increases the dipsogenic potency of intravenous angiotensin II and
      provides further support for the hypothesis that the dipsogenic action of
      intravenous angiotensin II is counteracted by the rise in blood pressure.

PMID- 2003588
TI  - Energy expenditure and substrate metabolism in ethanol-induced liver cirrhosis.
AB  - Energy expenditure and substrate metabolism were investigated in 10 patients with
      alcoholic liver cirrhosis (EtOH-Ci) and 10 healthy controls (C). Resting
      metabolic rate (RMR) varied from 1,269 to 2,467 kcal/day in C and from 1,228 to
      2,098 kcal/day in EtOH-Ci. RMR was significantly related to fat-free mass (FFM)
      in both groups, but EtOH-Ci decreased FFM and increased RMR when expressed per
      kilogram FFM (+33%). Glucose intolerance, hyperinsulinemia, and a decreased C
      peptide-to-insulin ratio were observed in EtOH-Ci after a test meal.
      Concomitantly, nonoxidative glucose metabolism was reduced in association with
      normal increases in glucose oxidation. EtOH-Ci reduced insulin sensitivity (-59%)
      and maximal insulin-dependent glucose disposal (-40%) during a sequential two
      step glucose clamp protocol (phase 1: 1 mU.kg body wt-1.min-1 insulin infusion
      rate + euglycemia; phase 2: 4 mU.kg body wt-1.min-1 insulin infusion rate + 165
      mg/dl plasma glucose concentration). This was explained by reduced glucose
      storage (-99%, -51%) in association with normal responses in glucose oxidation
      rate, plasma lactate concentration, lipid oxidation rate, and rate of
      lipogenesis. Defective glucose storage was independent of reduced FFM. EtOH-Ci
      increased glucose-induced thermogenesis by 57%. We conclude that increased
      resting metabolic rate, enhanced thermogenesis, defective glucose storage, and
      normal glucose oxidation together result in increased energy needs and favor
      negative energy balance in patients with alcoholic cirrhosis.

PMID- 2003589
TI  - Protein-induced changes in energy expenditure in young and old individuals.
AB  - Resting energy expenditure (EE) has recently been shown to be reduced in elderly
      human subjects even after adjustment for body size and composition. The present
      study extended this examination of EE in relation to age by comparing the thermic
      effect of a protein meal in young men (YM 20-26 yr, n = 9), old men (OM 70-89 yr,
      n = 9), and old women (OW 67-75 yr, n = 6). EE was measured before and from 1 to
      6 h after presentation of 60 g protein and of a control noncaloric meal on
      separate occasions. Despite substantial differences in body size and composition,
      the protein-induced increment in EE was similar in all groups [maximum increase:
      YM 0.21 +/- 0.05, OM 0.17 +/- 0.12, and OW 0.17 +/- 0.04 (SE) kcal/min]. Although
      fasting plasma norepinephrine (NE) levels differed among all three groups (YM
      less than OM less than OW), NE concentrations were not affected by protein
      ingestion. Because protein administration acutely promotes synthesis of dopamine
      (DA) and serotonin (5-HT), which are both capable of stimulating EE, blockade of
      extraneuronal synthesis of DA and 5-HT with carbidopa, a competitive inhibitor of
      aromatic-L-amino acid decarboxylase, failed to suppress (and actually increased)
      postprandial EE. These data demonstrate that not all mechanisms responsible for
      EE decline with age and that protein-induced changes in EE are more a function of
      the oral load itself than of the size, age, or antecedent diet of the individual
      ingesting the protein.

PMID- 2003590
TI  - Dose-related effects of epinephrine on glucose production in conscious dogs.
AB  - The effects of increases in plasma epinephrine from 78 +/- 32 to 447 +/- 75,
      1,812 +/- 97, or 2,495 +/- 427 pg/ml on glucose production, including
      gluconeogenesis, were determined in the conscious, overnight-fasted dog, using a
      combination of tracer [( 3-3H]glucose and [U-14C]alanine) and arteriovenous
      difference techniques. Insulin and glucagon were fixed at basal levels using a
      pancreatic clamp. Plasma glucose levels rose during the 180-min epinephrine
      infusion by 47 +/- 7, 42 +/- 22, and 74 +/- 25 mg/dl, respectively, in
      association with increases in hepatic glucose output of 1.04 +/- 0.22, 1.87 +/-
      0.23, and 3.70 +/- 0.83 mg.kg-1.min-1 (at 15 min). Blood lactate levels rose by
      1.52 +/- 0.24, 4.29 +/- 0.49, and 4.60 +/- 0.45 mmol/l, respectively, by 180 min,
      despite increases in hepatic uptake of lactate of 3.47 +/- 5.73, 12.83 +/- 3.46,
      and 37.00 +/- 4.20 mumol.kg-1.min-1. The intrahepatic gluconeogenic efficiency
      with which the liver converted the incoming alanine to glucose had risen by 84 +/
      40, 77 +/- 24, and 136 +/- 34% at 180 min, respectively. The latter effect plus
      the effect on net hepatic lactate uptake point to an intrahepatic action of high
      levels of the hormone in vivo. In conclusion, epinephrine produces dose-dependent
      increments in overall glucose production, which involve a progressive stimulation
      of both glycogenolysis (as assessed by glucose production at 15 min) and
      gluconeogenesis (assessed in the last 30 min of the study). The latter involves a
      peripheral action of the catecholamine to increase gluconeogenic substrate supply
      to the liver and may also involve a hepatic effect when high epinephrine levels
      are present.

PMID- 2003591
TI  - Naloxone augments muscle sympathetic nerve activity during isometric exercise in
      humans.
AB  - The influence of an endogenous opioid peptide (EOP) antagonist (naloxone, 1.2 mg
      iv bolus) on muscle sympathetic nerve activity (MSNA, microneurography) was
      studied on 19 young male and female volunteers. Isometric handgrip, cold pressor
      test, and acute baroreceptor unloading with sodium nitroprusside (autonomic
      stresses) were carried out under two conditions, one group (n = 11) before
      (control responses) and after naloxone and another group (n = 8) before and after
      placebo saline. Monitored cardiovascular variables included heart rate, central
      venous pressure (jugular vein catheter), arterial blood pressure (radial artery
      catheter), circulating catecholamines, and forearm blood flow. At rest,
      cardiovascular variables and MSNA were not affected by either naloxone or saline.
      MSNA (total activity = burst frequency x burst amplitude/100 cardiac cycles)
      increased during isometric handgrip to a greater extent (30 +/- 6 vs. 16 +/- 5
      arbitrary units) after naloxone compared with control trials (P less than 0.05).
      After naloxone, arterial systolic and diastolic blood pressures were higher
      during handgrip exercise. These augmented arterial pressures and MSNA responses
      were not evident during either the cold pressor test or the sodium nitroprusside
      stress. These data suggest that isometric muscle contraction elicits a
      sympathetic neural response that may be modified by EOP. This interaction is not
      evident during two other stresses, when sympathetic responses are equal to or
      greater than those provoked by isometric handgrip exercise.

PMID- 2003592
TI  - Dual mechanism of insulin action on human skeletal muscle: identification of an
      indirect component not mediated by FFA.
AB  - To determine whether insulin action on human skeletal muscle is entirely
      accounted for by a direct effect of insulin per se, we quantitated forearm
      glucose uptake (FGU) in two groups of normal subjects under conditions of
      identical forearm tissue insulinization (approximately 90 microU/ml) induced by
      means of systemic (group I) or intrabrachial insulin infusion (group II). With
      this approach, a difference of FGU between the two groups is demonstrative of the
      operation of indirect mechanisms in insulin action. During insulin infusion in
      group I, euglycemia was maintained by a variable glucose infusion, whereas
      arterial free fatty acid (FFA) concentration fell below 0.1 mM. In group II,
      arterial concentrations of both glucose and FFA remained unchanged, indicating
      that insulin effect was indeed restricted to the forearm tissues. With local
      insulin administration, FGU reached levels approximately 40% lower than those
      achieved with systemic insulin infusion (P less than 0.01-0.005). To determine
      whether this difference could be attributed to the fall in FFA concentration
      associated with systemic insulinization, FGU was also quantitated during a
      systemic insulin plus heparin infusion (group III) to maintain FFA at their basal
      levels. In this condition, insulin-stimulated FGU was not different from that
      observed in group I. These data demonstrate that 1) insulin action on skeletal
      muscle glucose disposal is mediated by a direct as well as an indirect component,
      and 2) the maintenance of basal FFA does not affect insulin-stimulated FGU,
      indicating that the indirect component of insulin action is mediated by a
      different mechanism.

PMID- 2003593
TI  - Growth hormone, cortisol, or both are involved in defense against, but are not
      critical to recovery from, hypoglycemia.
AB  - We tested the hypotheses that growth hormone, cortisol, or both are involved in
      defense against but are not critical to recovery from prolonged hypoglycemia and
      that the putative roles of these hormones in defense against prolonged
      hypoglycemia are permissive rather than direct. To do so we studied control
      subjects (n = 10) and patients with growth hormone and cortisol deficiencies
      resulting from hypopituitarism both in the untreated state (n = 7) and with
      prestudy and basal intrastudy growth hormone and cortisol replacement (n = 6).
      Postabsorptive plasma glucose, insulin, glucagon, and epinephrine concentrations
      were no different in the untreated patients and controls. Twelve-hour insulin
      infusions, in low doses adjusted over the 1st 2 h to produce plasma glucose
      concentrations of 3.6 mmol/l (65 mg/dl) and then fixed at that dose, resulted in
      significantly (P less than 0.0001) lower late plasma glucose concentrations in
      the patients, without and with replacement. The 12-h plasma glucose
      concentrations were 2.9 +/- 0.1 mmol/l (53 +/- 1 mg/dl) in the control subjects,
      2.4 +/- 0.1 mmol/l (43 +/- 2 mg/dl; P less than 0.001 vs. control) in the
      deficient patients, and 2.5 +/- 0.1 mmol/l (45 +/- 2 mg/dl; P less than 0.01 vs.
      control) in the replaced patients. Rates of glucose recovery from hypoglycemia
      after discontinuation of insulin were identical in all three studies. Thus growth
      hormone, cortisol, or probably both play a demonstrable role in defense against
      prolonged, in contrast to short-term, hypoglycemia in humans. This does not
      appear to be the result of permissive actions of the hormones and is therefore
      best attributed to their increments during hypoglycemia.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 2003594
TI  - Regulation of glucose utilization in human skeletal muscle during moderate
      dynamic exercise.
AB  - The effect of bicycle exercise (75% of maximal oxygen uptake) on glucose uptake
      by the inferior limb (LGU) and glycolysis in human skeletal muscle has been
      investigated. Biopsies were obtained from the quadriceps femoris muscle before
      exercise, after 5 and 40 min of exercise, and at fatigue [74.9 +/- 4.7 (SE) min].
      LGU was 0.05 +/- 0.02 mmol/min at rest, increased approximately sevenfold after 5
      min of exercise, and continued to increase linearly during the first 40 min of
      exercise. Thereafter LGU stabilized at approximately 1.4 mmol/min until fatigue.
      Intracellular glucose was low at rest but increased sixfold after 5 min of
      exercise (P less than 0.01 vs. rest); thereafter, intracellular glucose decreased
      and was not significantly different from the value at rest after 40 min or at
      fatigue (P greater than 0.05). D-Glucose 6-phosphate (G-6-P) and alpha-D-glucose
      1,6-bisphosphate (G-1,6-P2) (inhibitors of hexokinase) increased significantly
      after 5 min of exercise (approximately 300% G-6-P; approximately 25% G-1,6-P2)
      and then decreased continuously. The muscle glycolytic rate (glycogenolysis +
      glucose uptake) averaged 7.7 mmol.kg dry wt-1.min-1 during the first 40 min of
      exercise and 3.7 mmol.kg dry wt-1.min-1 during the last 35 min of exercise. The
      contribution of extracellular glucose to muscle glycolysis was estimated to be
      only 5 and 19% during the initial and latter phases of exercise, respectively. It
      is concluded that, during the initial phase of exercise, glucose utilization is
      limited by phosphorylation, probably due to G-6-P-dependent inhibition of
      hexokinase.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2003595
TI  - Suppression of insulin-like growth factor I during epidermal growth factor
      induced growth retardation.
AB  - Epidermal growth factor (EGF) attenuates growth when administered to rats less
      than 2 wk of age but lacks growth-retarding properties when given to older
      animals. Because the insulin-like growth factors (IGF) are postulated to be
      important regulators of somatic growth during the perinatal period, we examined
      the effect of exogenous EGF on serum and tissue concentrations of IGF-I and
      hepatic expression of mRNA for IGF-I and IGF-II. A single injection of EGF (500
      ng/g body wt) produced a significant (P less than 0.01) decline in serum IGF-I
      concentration within 4 h in newborn rat pups [controls, 46.2 +/- 9.1 (SD) ng/ml;
      EGF treated, 29.4 +/- 4.0 ng/ml] but was ineffective in 2-wk-old animals (control
      IGF-I, 72.8 +/- 15.1 vs. 64.0 +/- 13.7 ng/ml). When the EGF was given on days 0-3
      of life, circulating IGF-I concentrations were suppressed further (control, 61.4
      +/- 8.6; EGF treated, 32.5 +/- 8.6 ng/ml). Despite the change in circulating IGF
      I levels in the newborn rats, the amount of IGF-I extractable from liver and
      kidney of growth-retarded animals was not significantly different from control.
      Likewise, IGF-I and IGF-II mRNA expression in liver, as assessed by blot
      hybridization, was unchanged by the EGF treatment. The rapid decline in IGF-I
      concentration after EGF administration, coupled with the restriction of this
      phenomenon the first 2 wk of extrauterine life, implies that changes in IGF-I are
      involved in the pathogenesis of EGF-induced growth retardation.

PMID- 2003596
TI  - Epinephrine increases tricarboxylic acid cycle intermediates in human skeletal
      muscle.
AB  - The effects of epinephrine (E) and insulin infusions on the contents of
      tricarboxylic acid cycle intermediates (TCAI), adenine nucleotides and their
      catabolites, and amino acids in skeletal muscle have been investigated. Eight men
      were studied on two separate occasions: 1) during 120 min of euglycemic
      hyperinsulinemia (UH, approximately 5 mM; 40 mU.m-2.min-1) and 2) during UH while
      E was infused (UHE, 0.05 microgram.kg-1.min-1). Biopsies were taken from the
      quadriceps femoris muscle before and after each clamp. The sum of citrate,
      malate, and fumarate in muscle did not change significantly during UH (P greater
      than 0.05) but doubled during UHE (P less than 0.001). There were no significant
      changes in any of the adenine nucleotides, their catabolites (including inosine
      monophosphate), or aspartate during UH and UHE (P greater than 0.05); nor were
      there any significant changes in pyruvate or alanine contents during UH (P
      greater than 0.05). On the other hand, there were significant increases in
      pyruvate and alanine contents during UHE (P less than 0.01 and 0.05,
      respectively), suggesting that there was increased production of 2-oxoglutarate
      (a TCAI) via the alanine aminotransferase (ALT) reaction. It is concluded that E
      infusion increases the contents of TCAI in human skeletal muscle, and it is
      likely that at least part of the increase is attributable to increased flux
      through the ALT reaction.

PMID- 2003597
TI  - CNS stimulation does not affect hepatic venous glucose concentration in severely
      diabetic rats.
AB  - To assess the role of the central nervous system (CNS) in carbohydrate metabolism
      in diabetes, neostigmine was injected into the third cerebral ventricle in fed
      rats with streptozotocin (STZ; 80 mg/kg)-induced diabetes under pentobarbital
      sodium anesthesia. Changes in hepatic venous plasma glucose concentrations were
      monitored. Neostigmine injection caused no significant changes in the hepatic
      venous plasma glucose concentration in untreated diabetic rats, whereas the
      glucose level increased significantly in insulin-treated diabetic rats similarly
      to the changes in normal control animals. In diabetic rats, the plasma levels of
      glucagon, epinephrine, and norepinephrine were increased significantly by
      neostigmine. After various doses (35-80 mg/kg) were given to rats, it was found
      that the higher the STZ dose, the lower was the hepatic glycogen content and the
      smaller was the glycemic response to neostigmine. Our results indicate that, in
      severe diabetes, CNS stimulation with neostigmine fails to increase hepatic
      glucose output, because glycogen stores are nearly exhausted and gluconeogenesis
      is already maximal.

PMID- 2003598
TI  - Interrelationship between hepatic ureagenesis and gluconeogenesis in early
      sepsis.
AB  - This study was performed to investigate the interrelationship between
      gluconeogenesis and ureagenesis during sepsis. In isolated perfused livers,
      gluconeogenesis was assessed using either lactate or a combination of lactate,
      glutamine, and alanine as substrate. Ureagenesis was assessed using either NH4Cl
      or glutamine plus alanine as substrate. NH4Cl stimulated urea production in
      livers from both septic and sham-operated control rats. Urea release was
      approximately 1.2 and 2.0 mg urea nitrogen.g-1.h-1 for 1 and 5 mM NH4Cl,
      respectively, and was equal for both groups. With amino acids as substrate, urea
      production was significantly greater in livers from septic animals compared with
      controls. Phenylephrine stimulated urea production in the sham-operated group by
      about twofold, whereas in the septic group urea release was slightly inhibited.
      Gluconeogenesis from lactate was inhibited by NH4Cl (1 and 5 mM) in both groups,
      with no difference between groups. In contrast to enhanced ureagenesis from amino
      acids in septic rats, gluconeogenesis was decreased by approximately 24% (P less
      than 0.5). Similarly, phenylephrine (1 microM) stimulated gluconeogenesis by 13
      +/- 1 mumol.g-1.h-1 in sham-operated rats but only by 9 +/- 1 mumol.g-1.h-1 in
      septic rats (P less than 0.02). These results suggest that hepatic gluconeogenic
      and ureagenic pathways are intact in sepsis but that altered substrate preference
      and hormone sensitivity may result in decreased gluconeogenesis in the presence
      of elevated amino acid levels.

PMID- 2003599
TI  - Decreased expression of glucose transporter in muscle from insulin-resistant
      patients.
AB  - We have observed that in vitro incubated human muscle fiber strips from obese
      patients with or without non-insulin-dependent diabetes mellitus (NIDDM) have
      reduced insulin-stimulated glucose transport rates compared with nonobese control
      patients. To investigate if the decrease in glucose transport is associated with
      a depletion of glucose transport protein, we performed Western blot analysis of
      muscle samples from nonobese control, obese nondiabetic, and obese NIDDM patients
      to measure the levels of the muscle-adipose tissue glucose transporter (GLUT-4)
      protein. Glucose transporter protein was depressed by 23% in the obese
      nondiabetic and 18% in the obese NIDDM group. The results were essentially the
      same in the rectus abdominus and vastus lateralis muscles. These data suggest
      that the decreased glucose transport rate observed in muscle of these obese
      patients with or without NIDDM may be due, at least in part, to a decreased
      expression of the "insulin-sensitive" (GLUT-4) glucose transporter. This
      alteration may play a role in the insulin resistance seen in obesity and
      diabetes.

PMID- 2003600
TI  - Protein kinase C in uterine and systemic arteries during ovarian cycle and
      pregnancy.
AB  - Elevated uterine blood flow is associated with increases in local estrogen-to
      progesterone ratios during the follicular phase of the ovarian cycle and late
      pregnancy. Because protein kinase C (PKC) activation increases arterial tone,
      decreased PKC activity may mediate vasodilation. Therefore, we determined uterine
      (UA) and systemic artery (SA, omental) PKC activity (pmol.mg protein-1.min-1)
      during the follicular (n = 6), early luteal (n = 4), and late luteal (n = 3)
      phases of the sheep ovarian cycle, and at 110 +/- 3 (n = 4) and 130 +/- 1 (n = 8)
      (+/- SE) days of ovine gestation. The stage of the ovarian cycle was verified by
      the presence of follicles (high estrogen) or corpora lutea (high progesterone) on
      the ovary and by plasma estrogen and progesterone concentrations. UA-PKC activity
      (pmol.mg protein-1.min-1) during the follicular phase was 100 +/- 18 and
      increased progressively to 155 +/- 28 during the early luteal phase and to 219 +/
      37 (P less than 0.05) during the late luteal phase; SA-PKC activity was
      unchanged. A local utero-ovarian relationship was observed, i.e., UA-PKC activity
      was lower (P less than 0.001) in UA ipsilateral to ovaries with only follicles
      (105 +/- 14) when compared with UA adjacent to ovaries with corpora lutea (224 +/
      26), which was similar to SA-PKC activity (184 +/- 35). UA-PKC activity fell
      from 344 +/- 70 at 110 days to 109 +/- 12 at 130 days gestation (P less than
      0.05); SA-PKC activity was unchanged. During the ovarian cycle and latter one
      third of ovine pregnancy, increased estrogen production is associated with
      decreased UA-PKC activity; thus local ovarian and placental steroids may alter
      PKC activity, thereby regulating UA tone and blood flow.

PMID- 2003601
TI  - Effect of dietary calcium on bone density in growing rabbits.
AB  - Reductions in peak bone mass at skeletal maturity may increase the risk for the
      subsequent development of osteoporosis. Although changes in calcium intake can
      modify the rate of decline in bone density in the mature skeleton, longitudinal
      assessments of the effect of dietary calcium supplementation during skeletal
      growth on peak bone mass have not been done in humans or experimental animals.
      Thus quantitative computed tomography (QCT) was used to monitor changes in
      vertebral bone density at 6-wk intervals during growth from 8 wk of age until
      skeletal maturity at 35 wk in male New Zealand White rabbits maintained on diets
      containing 0.15% (low Ca), 0.45% (normal Ca), or 1.35% (high Ca) calcium. Serum
      parathyroid hormone (PTH) and calcitriol levels increased, and renal calcium
      excretion decreased in low Ca compared with normal Ca; in contrast, serum
      calcitriol levels decreased and renal calcium excretion increased from control
      values in high Ca. Vertebral bone density by QCT did not differ during growth
      between high Ca and normal Ca, and peak values at epiphyseal closure also did not
      differ in these two groups. Vertebral bone density was lower, however, throughout
      the study in low Ca, and peak values at epiphyseal closure remained below those
      in either normal Ca or high Ca. Quantitative bone histology revealed decreases in
      cortical thickness in the third lumbar vertebra in low Ca, whereas trabecular
      bone area did not differ among groups; there was no histological evidence of
      osteomalacia in low Ca. Thus dietary calcium restriction during growth reduces
      peak bone mass at skeletal maturity, but raising dietary calcium intake above
      normal levels does not increase peak bone mass in this experimental model.

PMID- 2003602
TI  - Growth hormone acutely stimulates forearm muscle protein synthesis in normal
      humans.
AB  - The short-term effects of growth hormone (GH) on skeletal muscle protein
      synthesis and degradation in normal humans are unknown. We studied seven
      postabsorptive healthy men (age 18-23 yr) who received GH (0.014 micrograms.kg
      1.min-1) via intrabrachial artery infusion for 6 h. The effects of GH on forearm
      amino acid and glucose balances and on forearm amino acid kinetics [( 3H]Phe and
      [14C]Leu) were determined after 3 and 6 h of the GH infusion. Forearm deep vein
      GH rose to 35 +/- 6 ng/ml in response to GH, whereas systemic levels of GH,
      insulin, and insulin-like growth factor I (IGF-I) were unchanged. Forearm glucose
      uptake did not change during the study. After 6 h, GH suppressed forearm net
      release (3 vs. 6 h) of Phe (P less than 0.05), Leu (P less than 0.01), total
      branched-chain amino acids (P less than 0.025), and essential neutral amino acids
      (0.05 less than P less than 0.1). The effect on the net balance of Phe and Leu
      was due to an increase in the tissue uptake for Phe (71%, P less than 0.05) and
      Leu (37%, P less than 0.005) in the absence of any significant change in release
      of Phe or Leu from tissue. In the absence of any change in systemic GH, IGF-I, or
      insulin, these findings suggest that locally infused GH stimulates skeletal
      muscle protein synthesis. These findings have important physiological
      implications for both the role of daily GH pulses and the mechanisms through
      which GH can promote protein anabolism.

PMID- 2003603
TI  - Neutrophil and Kupffer cell-induced oxidant stress and ischemia-reperfusion
      injury in rat liver.
AB  - The hypothesis that Kupffer cells and infiltrating neutrophils generate reactive
      oxygen in the hepatic sinusoids and may contribute to ischemia-reperfusion injury
      in the liver was investigated in a model of partial no-flow ischemia and
      reperfusion in male Fischer rats in vivo. During the reperfusion period of 60
      min, plasma concentrations of glutathione disulfide (GSSG; index of oxidant
      stress) increased from 1.62 +/- 0.20 microM glutathione (GSH) equivalents to
      maximal values of 11.82 +/- 1.45 (45 min ischemia), 24.19 +/- 2.35 (60 min
      ischemia), and 70.20 +/- 7.8 (120 min ischemia). The basal tissue GSSG content in
      the postischemic lobes (0.19 +/- 0.02 nmol GSH eq/mg protein) increased by 50
      100%. Although the number of neutrophils in liver and lung increased by 3- to 10
      fold during reperfusion, there was no positive correlation between the number of
      neutrophils and the GSSG concentrations measured in plasma or tissue. However,
      activation of Kupffer cells with high doses of retinol or with Propionibacterium
      acnes significantly enhanced plasma GSSG levels, while inactivation of Kupffer
      cells with methyl palmitate or gadolinium chloride significantly attenuated the
      increase of plasma GSSG. Inactivation of Kupffer cells protected the liver
      significantly against ischemia-reperfusion injury. It is concluded that Kupffer
      cells are the predominant source of reactive oxygen formed during the initial
      reperfusion period and that Kupffer cell activity (including reactive oxygen
      formation) contributes to reperfusion injury in the liver in vivo.

PMID- 2003604
TI  - Sensory neurons mediate protective vasodilatation in rat gastric mucosa.
AB  - Sensory nerve stimulation by intragastric capsaicin (160 microM) prevents ethanol
      injury to the gastric mucosa and facilitates gastric mucosal blood flow (GMBF).
      The present study examined whether the capsaicin-induced increase in GMBF
      accounts for mucosal protection. Gastric perfusion of capsaicin (160 microM) in
      urethan-anesthetized rats did not change blood pressure but significantly
      enhanced GMBF as measured by hydrogen gas clearance. The same increase in GMBF
      was seen when capsaicin was administered together with an injurious concentration
      of ethanol (25%). GMBF was facilitated by capsaicin in a dose-related manner (10
      640 microM), and the dose-dependent vasodilatation was significantly correlated
      with a dose-dependent reduction of gross damage to the mucosa. Histology showed
      that capsaicin prevented deep but not superficial mucosal damage. The vasodilator
      and protective effects of capsaicin resulted from stimulation of sensory neurons
      and propagation of nerve activity, since they were blocked after ablation of
      capsaicin-sensitive neurons or local intra-arterial infusion of tetrodotoxin.
      This and the finding of a limited access of intragastric capsaicin to the gastric
      wall indicates that the vasodilator and protective effects of capsaicin are
      mediated by a neural reflex. It is concluded that facilitation of GMBF is the
      major mechanism of sensory nerve-mediated prevention of gastric mucosal injury.

PMID- 2003605
TI  - Nitric oxide mediating NANC inhibition in opossum lower esophageal sphincter.
AB  - Strips from opossum lower esophageal sphincter were prepared and mounted in organ
      baths for recording of isometric tension. Nonadrenergic, non-cholinergic (NANC)
      inhibitory responses were evoked by transmural field stimulation. The relaxant
      responses to field stimulation were inhibited in a concentration-dependent manner
      by N omega-nitro-L-arginine (L-NNA), a substance known to inhibit the formation
      of nitric oxide (NO). At a concentration at 10(-4) M of L-NNA, most preparations
      contracted during field stimulation, and this response was abolished by atropine
      (10(-6) M). L-Arginine (10(-5) M) shifted the concentration-response curve for L
      NNA to the right. Relaxant responses to VIP (10(-9) to 10(-6)M) and sodium
      nitroprusside (10(-9) to 10(-5) M) were unaffected by preincubation with L-NNA
      (10(-5) to 10(-4) M) or L-arginine (10(-5) M). The inhibition of NANC-relaxation
      was apparently not due to an influence on release of a NANC transmitter different
      from NO, since L-NNA had no preserving effects on responses to field stimulation
      in preparations treated with scorpion venom. We conclude that involvement of a NO
      generating process from L-arginine seems mandatory for NANC responses in the
      isolated lower esophageal sphincter.

PMID- 2003606
TI  - Correlation between electrical and morphological properties of canine pyloric
      circular muscle.
AB  - Electrical slow waves decay in amplitude as they conduct from the myenteric to
      the submucosal regions of the circular muscle layer in the canine pyloric
      sphincter. We used the partitioned chamber method to study the passive and active
      properties of pyloric muscles, and we found that length constants of circular
      muscles of myenteric region were significantly longer than muscles near the
      submucosal surface. These data suggested differences in either membrane
      resistance, junctional resistance, or cytoplasmic resistance. The first parameter
      was evaluated by measuring time constants in intact tissues and single cells
      isolated from the submucosal and myenteric regions. Membrane time constants were
      not different in the two regions, nor were differences found in the input
      resistances of isolated cells. Morphological studies failed to demonstrate
      differences in cell diameters in the two regions suggesting that cytoplasmic
      resistances are similar. These findings suggest that the different cable
      properties in the two regions may be due to differences in electrical coupling.
      Morphological examination revealed similar numbers of gap junctions between cells
      in the two regions, but large differences were noted in the size of muscular
      bundles. Muscles of the myenteric region were arranged into large, tightly packed
      bundles, whereas muscles of the submucosal region consisted of small bundles with
      an extensive extracellular space filled with connective tissue. We suggest that
      the difference in cable properties may be due to differences in electrical
      coupling between bundles. These data suggest that submucosal muscles function
      more like a multiunit smooth muscle, whereas myenteric muscles behave as a single
      unit.

PMID- 2003607
TI  - Role of blood flow and alkaline secretion in acid-induced deep duodenal villous
      injury in rats.
AB  - The effect of 16,16-dimethylprostaglandin E2 (dmPGE2) and corticotropin-releasing
      factor (CRF) on duodenal blood flow, alkaline secretion, and acid-induced deep
      duodenal villous injury was studied. The duodena of anesthetized rats were
      prepared for simultaneous measurement of alkaline secretion by back titration,
      and blood flow by hydrogen gas clearance; or for perfusion with 0.1 N HCl and
      histological examination of villous injury. The results revealed that the dmPGE2
      induced increase in basal alkaline secretion (due solely to an increase in the
      volume of secretion) appears to be a better predictor of protection against
      exogenous acid-induced deep duodenal villous injury than rise in duodenal blood
      flow, since CRF induces a similar rise in duodenal blood flow but does not
      enhance alkaline secretion or reduce acid-induced villous damage. The absence of
      a greater loss of H+ during acid perfusion of the duodenum in the dmPGE2-treated
      rats, however, suggests that the mechanism of the dmPGE2 protection against acid
      induced deep duodenal villous injury cannot be explained entirely by its ability
      to increase basal duodenal alkaline secretion.

PMID- 2003608
TI  - Expression of cobalamin transport proteins and cobalamin transcytosis by colon
      adenocarcinoma cells.
AB  - Human colon adenocarcinoma (Caco-2) cells express both intrinsic factor-cobalamin
      receptor and transcobalamin II (TC II). The expression of these activities began
      to rise by day 6 and reached peak levels between 10 and 15 days in culture. The
      postconfluent Caco-2 cell membranes bound approximately 30-35 fmol of intrinsic
      factor (IF) [57Co]Cbl/mg protein. The size of the mature receptor expressed in
      the apical brush border had a relative molecular mass of 230 kDa. The
      intracellular form of TC II had a Mr of 43, 5 higher than the secreted form of TC
      II. TC II was secreted unidirectionally via the basolateral direction when Caco-2
      cells were grown on culture inserts. When grown on culture inserts, the Caco-2
      cells were polarized (electrical resistance greater than 200 omega/cm2) and
      transcytosed [57Co]Cbl bound to IF from apical-to-basal but not from basal-to
      apical direction. Under these conditions, [57Co]Cbl complexed to haptocorrin was
      not transported. These cells also transcytosed free [57Co]Cbl, although less
      efficiently. The [57Co]Cbl transcytosed using either IF[57Co]Cbl or free
      [57Co]Cbl as ligands was bound exclusively to TC II. Intracellular [57Co]Cbl
      decreased during transcytosis with a slow (t1/2 = 4 h) transfer of [57Co]Cbl from
      IF to TC II. These results show that the transport of Cbl in Caco-2 cells is very
      similar to the human enterocyte system.

PMID- 2003609
TI  - Volitional augmentation of upper esophageal sphincter opening during swallowing.
AB  - Studies were done on eight normal subjects with synchronized videofluoroscopy and
      manometry to facilitate a biomechanical analysis of the extent and mechanism of
      voluntary augmentation of upper esophageal sphincter (UES) opening during
      swallowing. Movements of the hyoid and larynx, dimensions of sphincter opening,
      and intraluminal pressure events were determined at 1/30-s intervals during
      swallows of 1 and 10 ml of liquid barium. Swallows of each volume were obtained
      both before and after subjects were taught a maneuver designed to augment UES
      opening, the Mendelsohn maneuver (voluntary prolongation of laryngeal excursion
      at the midpoint of the swallow). At either volume, use of the maneuver increased
      the duration of the anterior-superior excursion of the larynx and hyoid and
      consequently delayed sphincter closure by maintaining traction on the anterior
      sphincter wall. The onset of the pharyngeal contraction (the event normally
      culminating in sphincter closure) was not affected by the maneuver. We conclude
      that swallow-related hyoid motion, laryngeal motion, and UES opening are subject
      to volitional augmentation, supporting the notion that biofeedback techniques can
      be used to modify impaired swallowing.

PMID- 2003610
TI  - Contrasting effects of PGE2 and PGD2: ion transport in the canine proximal colon.
AB  - Our earlier study [Am. J. Physiol. 256 (Gastrointest. Liver Physiol. 19): G673
      G679, 1989] showed that the isomers prostaglandin E2 and D2 (PGE2 and PGD2) had
      contrasting effects on the canine proximal colonic epithelium in vitro. Whereas
      PGE2 produced sharp increases in short-circuit current (Isc), PGD2 rapidly
      reversed these changes. We report here that PGD2 reversed increases in Isc
      produced by other agonists (forskolin, carbachol) and was thus not a specific
      antagonist to PGE2. The transient increase in Isc and conductance produced by
      PGE2 were accompanied by alterations in Cl- but not Na+ fluxes. These were
      partitioned into early and late phases. In the early phase, net Cl- flux (JCl
      net) decreased due to a reduction in Cl- mucosal to serosal flux (JCl-m----s) and
      increases in JCl-s----m. In the later phase, these changes appeared to revert to
      prestimulation values. Because forskolin produced more sustained increases in
      Isc, we used it as an agonist to define the effects of PGD2 on ion fluxes.
      Forskolin produced a marked reduction in JCl-net due to a decrease in JCl-m----s
      and an increase in JCl-s----m. PGD2 not only reversed the increases in Isc and
      conductance produced but also reversed the changes in Cl- flux.

PMID- 2003611
TI  - Efferent pathways in the reflex control of gastric emptying in rats.
AB  - Previous studies have established that acid, hypertonic, or protein-rich liquid
      test meals delay gastric emptying by reflex pathways involving the extrinsic
      innervation of the gut. To characterize the efferent pathways involved in these
      reflexes, we have studied the emptying of liquid test meals in control rats and
      in rats after celiac ganglionectomy, pyloroplasty, and treatment with
      guanethidine or 6-hydroxydopamine, and in rats with circulating vasoactive
      intestinal polypeptide (VIP) antibodies. The results suggest that the action of
      hypertonic solutions on gastric emptying requires an intact celiac ganglion, that
      acid requires an intact pylorus, and that the action of protein-rich meals is
      suppressed by VIP antibodies. Sympathetic adrenergic neurons do not apparently
      mediate the gastric emptying of any of these solutions. The results suggest that
      there are at least three different reflexes by which the different components of
      a mixed meal might control gastric emptying. The results are also consistent with
      the idea that vagovagal reflexes mediate the action of protein-rich solutions on
      gastric emptying in rats.

PMID- 2003612
TI  - Measurement of tone in canine colon.
AB  - We sought to determine whether the proximal colon modifies its capacity to
      accommodate contents by altering the tone within its wall. In dogs equipped with
      manometric recorders in the terminal ileum and proximal colon, a highly compliant
      bag was introduced into the proximal colon. With the use of an electromechanical
      barostat, the capacity of the colonic segment was monitored at a constant low
      distending pressure; the volume of air required to maintain a preset pressure in
      the bag was recorded by the barostat. During fasting, rhythmic cycles of volume
      were recorded, with a cycle frequency of approximately 1/min. Importantly, this
      phenomenon was not related to the simultaneous recording of manometric pressures
      in the adjacent bowel or to the interdigestive cycle (phase III) in the ileum.
      Peristaltic-like pressure complexes (recorded manometrically) in the ileocolonic
      region were associated with receptive relaxation of the proximal colon. Feeding,
      bethanechol, and morphine reduced volumes accommodated in the bag, presumably by
      increasing tone in the wall of the colon. Atropine had the opposite effect. These
      results support the concept that tonic changes in the wall of the proximal colon,
      which could influence accommodation and storage in the large bowel, are not
      always recorded by conventional techniques.

PMID- 2003613
TI  - Shortening of the esophagus in response to swallowing.
AB  - Esophageal shortening accompanies peristalsis in laboratory animals and is
      attributed to longitudinally oriented fibers in esophageal muscle layers. To
      evaluate this phenomenon in humans, esophageal shortening during suspended
      respiration in response to swallows was measured in five normal volunteers
      (median age, 23 yr). Metal mucosal clips were endoscopically placed at and 10 cm
      above the gastroesophageal junction, and their movement was recorded by
      videotaped fluoroscopy. All subjects demonstrated esophageal shortening with each
      swallow in a characteristic pattern with small interswallow variance. Early,
      minimal shortening of the proximal segment (6.0 +/- 2.4 mm) was followed by
      delayed, prominent distal segment shortening (18.9 +/- 9.3 mm) that principally
      accounted for overall change in total esophageal length (18.0 +/- 8.1 mm). The
      degree of esophageal shortening did not correlate with circular muscle
      contraction wave parameters that were obtained with intraluminal manometrics in a
      separate study (P greater than 0.2 for each correlation), and distal segment
      shortening uniformly preceded the onset of contraction waves in the same region.
      These findings indicate that patterned esophageal shortening with swallows occurs
      in humans, most prominently in the distal esophagus. The technique may be useful
      in determining the participation of axial esophageal movement in esophageal
      motility disorders.

PMID- 2003614
TI  - pH-sensitive anion exchanger in rat lacrimal acinar cells.
AB  - Basolateral membranes from rat lacrimal acinar cells contain Na(+)-H+ and Cl(-)
      HCO3- antiport activities [Invest. Ophthalmol. Visual Sci. 28: 1726-1729, 1989;
      Am. J. Physiol. 255 (Gastrointest. Liver Physiol. 18): G367-G373, 1988]. This
      study evaluated factors involved in coupling ion fluxes through these
      antiporters. 22Na+ flux into acini isolated from rat exorbital glands was 94 +/-
      6 nmol.mg-1.min-1, and it was accelerated threefold by 10(-5) M carbachol;
      neither resting nor stimulated influx was affected by bumetanide. It is,
      therefore, likely that a portion of the carbachol-dependent Na+ influx is
      mediated by Na(+)-H+ antiporters. 36Cl- flux into Cl(-)-loaded, unstimulated
      acini was 275 +/- 21 nmol.mg-1.min-1; Cl- flux into HCO3(-)-loaded acini was 204
      +/- 2; Cl- flux into acini loaded with both Cl- and HCO3- was 253 +/- 32; and
      influx in the absence of exchangeable intracellular anions was 176 +/- 13.
      Therefore, Cl(-)-Cl- self-exchange represented the major component of anion
      exchanger-mediated Cl- flux into resting cells. As pHi was increased above 7.2 by
      potassium-nigericin pH clamping, Cl- fluxes into Cl(-)- and HCO3(-)-containing
      acini, but not into Cl(-)-depleted acini, were significantly accelerated. SITS
      completely abolished the pHi-activated increment of Cl(-)-Cl- exchange. Carbachol
      increased Cl- unidirectional flux into Cl(-)-loaded cells by 25% (P less than
      0.1), apparently as a result of Na(+)-H+ antiporter-mediated cytoplasmic
      alkalinization.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2003615
TI  - Strong gastric contractions cause mucosal ischemia.
AB  - Contractions of a segment of bowel result in alterations of its blood flow.
      However, the precise temporal and spacial relationships between contractions and
      mucosal blood flow are unknown. Rats were fitted with strain gauge force
      transducers and implanted with silver wire electrodes into the muscularis externa
      of the stomach. In vivo microscopic observation of motility and of the gastric
      mucosal blood flow was performed during electrical field-stimulated contractions.
      Contractions originated in the midcorpus, were 0.237 +/- 0.018 cm wide, traveled
      along the corpus at 0.133 +/- 0.024 cm/s, and had a duration of 5.9 +/- 0.1 s.
      Antral contractions were 0.174 +/- 0.032 cm wide, traveled at 0.070 +/- 0.009
      cm/s, and had a duration of 5.6 +/- 0.7 s. During the contraction, capillary flow
      velocity in the corpus decreased from a basal value of 410 +/- 105 to 206 +/- 104
      microns/s at the peak of a contraction. Five seconds after the contraction was
      released hyperemia was observed with the flow velocity increasing to 570 +/- 102
      microns/s. In the antrum, flow stopped completely during the contraction
      irrespective of the initial flow velocity and no hyperemia occurred with release
      of the contraction; rather, flow velocity slowly returned to baseline values. In
      both regions the flow reductions were in phase with the contractions as measured
      by the force transducers. These studies provide direct evidence that strong
      gastric contractions can effectively reduce or stop gastric mucosal blood flow.

PMID- 2003616
TI  - The Nursing Minimum Data Set: a major priority for public health nursing but not
      a panacea.

PMID- 2003617
TI  - Health policy: if you don't know where you're going, any road will take you.
AB  - It is not surprising that our health care system seems stalled in a developmental
      time warp, insulated from pressures to change. Everybody knows what should be
      changed, but changed to what? There is no national health policy that provides
      the context to redesign the health care system or even plan its incremental
      improvement. The self-interest ethos of the 1980s allowed decades of health and
      social advances to be rescinded with hardly a whisper of outrage. The more
      sophisticated our medical technology became, the more indifferent was the
      response to the real health needs of our society. Neither a society nor a health
      care system can survive without virtue or a cause that supersedes individual
      interests. Our health care cannot progress without an articulated purpose, a
      common vision expressed as policy that eliminates ambiguity of purpose,
      ambivalence towards performance standards, conflicts of principles, and
      contradictions of goals. The challenge calls for great leadership--to define
      policies that reverse the decline in both the indices of health and the political
      will to address the public good. To attempt less would allow this country's
      health care system to go down any road the vagaries of our political process take
      it.

PMID- 2003618
TI  - The Nursing Minimum Data Set: abstraction tool for standardized, comparable,
      essential data.
AB  - The Nursing Minimum Data Set (NMDS) represents the first attempt to standardize
      the collection of essential nursing data. These minimum core data, used on a
      regular basis by the majority of nurses in the delivery of care across settings,
      can provide an accurate description of nursing diagnoses, nursing care, and
      nursing resources used. Collected on an ongoing basis, a standardized nursing
      data base will enable nurses to compare data across populations, settings,
      geographic areas, and time. Public health nurses will be able to evaluate and
      compare services. The purpose of this article is to discuss briefly the following
      aspects of the NMDS: background including definition, purposes, and elements;
      availability and reliability of the data; benefits; implications of the NMDS with
      emphasis on nursing research; and health policy decision making.

PMID- 2003619
TI  - Regular source of ambulatory care and access to health services.
AB  - BACKGROUND: To examine why people lack a regular source of ambulatory care (RSAC)
      and explore whether this commonly used access measure accurately identifies
      population subgroups at risk for barriers to continuity care. METHODS: Using data
      from a 1986 national telephone survey, we performed a content analysis of
      subjects' verbatim reports as to why they lacked an RSAC (n = 5,748). RESULTS:
      The 16.4 percent of respondents who lacked an RSAC gave the following reasons: 1)
      financial problems, 8 percent; 2) local resource inaccessibility, 5 percent; 3)
      not wanting a regular source of ambulatory care, 61 percent; and 4) transitory
      loss of their regular source of ambulatory care, 18 percent. However, some
      sociodemographic subgroups reported substantially more problems with access
      barriers, and these disparities were often not detected by the global measure,
      RSAC. The poor were not more likely than the non-poor to lack an RSAC (odds ratio
      [OR] = 0.8; 95% confidence interval, [0.6, 1.1]), but were much more likely to
      lack an RSAC for financial reasons (OR = 5.2 [2.6, 10.6]). Similarly, rural
      respondents were not more likely than urban dwellers to lack an RSAC, but were
      more likely to lack an RSAC because of local resource inaccessibility (OR = 5.8
      [2.8, 11.9]). CONCLUSIONS: We conclude that the global measure, RSAC, is not an
      accurate indicator of whether population subgroups have access barriers to
      obtaining a source of continuity care.

PMID- 2003620
TI  - A community-based study of the use of chiropractic services.
AB  - BACKGROUND: Little population-based information is available on the use of
      chiropractic services. METHODS: We analyzed data from the RAND Health Insurance
      Experiment (HIE), a community-based study of the use of health services.
      Insurance claim forms for all fee-for-service patients who completed the study
      were examined for all visits coded as being seen by a chiropractor. Services
      provided and patient-specified symptoms were taken from these forms. Population
      based use rates were calculated for each HIE site. Use rates and services were
      calculated separately for first visits and repeat visits. RESULTS: There were
      5,279 persons who contributed 19,021 person-years of exposure during the study;
      395 different persons used 7,873 chiropractic services for a visit rate of 41 per
      100 person-years and rate of use of 7.5 percent. Forty-two percent of all visits
      were for pain in the back. Spinal manipulation accounted for 61 percent of all
      services provided. Compared to non-users, users tended to be White, middle-aged,
      married, and high school educated. Seven-fold geographic variations in the use of
      chiropractic services were seen. CONCLUSIONS: Chiropractors deliver a substantial
      amount of health care to the US population, and there are significant geographic
      variations in the rate and intensity of use of chiropractic services.

PMID- 2003621
TI  - Morbidity and disability in older persons in the years prior to death.
AB  - BACKGROUND: A large proportion of the disease and disability which affects older
      persons occurs in the years just prior to death. Little prospective evidence is
      available which quantifies the burden of morbidity and disability during these
      years. METHODS: In three community-based cohorts of persons age 65 and older,
      chronic conditions and disability were evaluated for the three years prior to
      death in 531 persons who had three annual assessments and then died within one
      year of the third assessment. Number of chronic conditions, prevalence of
      disability in activities of daily living (ADLs), and prevalence of disability on
      a modified Rosow-Breslau scale were determined for these decedents and compared
      to 8821 members of the cohorts known to have survived. RESULTS: Prevalence rates
      of disease and disability increased during the follow-up for both decedents and
      survivors, with decedents generally having higher rates than survivors.
      Disability rates prior to death, but not the number of diseases, increased with
      increasing age at death. The odds ratio for disability in ADLs at any of the
      three assessments for decedents versus survivors ranged from 3.0 to 4.2 in the
      three communities. In each community the odds ratio for ADL disability was higher
      in women decedents versus survivors than in men decedents versus survivors.
      CONCLUSIONS: These results have important implications for disability levels in
      future older populations in which death is projected to occur at increasingly
      higher ages.

PMID- 2003622
TI  - The yield of cholesterol screening in an urban black community.
AB  - BACKGROUND: While the distribution of cholesterol levels have been well studied
      in the general population, little is known about cholesterol and other
      cardiovascular disease risk factors in screenings held in an urban Black
      community. This study was designed to determine the yield of cholesterol
      screening in this community. METHODS: Screening took place in eight community
      sites. Serum total cholesterol was measured using a rapid capillary technique.
      Blood pressure was taken according to national guidelines and the average of two
      to three measurements were used. Standard interviews were used to determine the
      presence of cardiovascular risk factors by history. RESULTS: Of the 562
      individuals screened, 44.9 percent had cholesterol levels requiring referral for
      follow-up care. Of those with total cholesterol greater than or equal to 6.21
      mmol/L, 66.4 percent were previously undetected and more than half also had blood
      pressure levels greater than or equal to 140/90 mmHg on screening; 45 percent of
      all participants had blood pressure greater than or equal to 140/90 on
      screenings. Of those with a history of elevated total cholesterol levels, none
      had levels below 5.17 mmol/L at the time of screening. CONCLUSIONS: Multiple risk
      factors are highly prevalent in the urban Black community during cholesterol
      screening programs. Findings suggest the need for cholesterol programs
      incorporating blood pressure screening in the urban Black community.

PMID- 2003623
TI  - Alcohol drinking patterns and blood pressure.
AB  - BACKGROUND: Although blood pressure tends to increase with average alcohol
      consumption, little is known about the effects of drinking patterns on blood
      pressure. Therefore, the effects of average drinks per day and drinking pattern
      (defined as the independent and interactive effects of quantity and frequency) on
      blood pressure were compared. METHODS: Data were obtained from a random sample
      survey of 1,635 household residents in Erie County, New York. Alcohol-blood
      pressure relationships were examined using multiple regression analyses that
      controlled for the potentially confounding influence of 13 additional risk
      factors for elevated blood pressure. RESULTS: Consistent with prior research, a
      positive relationship was found between average drinks per day and diastolic and
      systolic blood pressure. Analyses examining the effect of drinking pattern
      indicated that drinking frequency had a positive effect on both diastolic and
      systolic blood pressure, whereas drinking quantity did not affect either.
      Furthermore, there was little evidence that the frequency-by-quantity interaction
      affected blood pressure. CONCLUSIONS: Low average alcohol intake and low blood
      pressure were associated with infrequent drinking, rather than with frequent
      drinking of small amounts of alcohol. Results suggest that the standard practice
      of averaging alcohol consumption may obscure important effects of drinking
      frequency on health.

PMID- 2003624
TI  - Caffeine consumption during pregnancy and fetal growth.
AB  - BACKGROUND: The purpose of this study was to examine the association between
      maternal caffeine consumption and low birthweight, intrauterine growth
      retardation, and prematurity, adjusting for multiple confounders. METHODS: Data
      obtained from birth certificates and interviews on 1,230 women with singleton
      live births were analyzed to evaluate the potential influence of caffeine
      consumption during the first trimester on fetal growth. RESULTS: The crude odds
      ratio for intrauterine growth retardation in infants of women reporting heavy
      caffeine consumption (greater than 300 mg/day) was 3.86 (95% CI = 1.80, 8.40)
      which decreased to 2.90 (95% CI = 1.23, 6.87) after controlling for confounding
      factors. The adjusted odds ratio for low birthweight and heavy maternal caffeine
      consumption was also elevated (OR = 2.05; 95% CI = 0.86, 4.88). Women who reduced
      their caffeine intake from greater than 300 mg/day to less than that early in
      pregnancy had lower risks of delivering infants with either intrauterine growth
      retardation or low birthweight than women who continued to consume that amount.
      Preterm delivery appeared to be unrelated to caffeine consumption. CONCLUSIONS:
      Taken together with studies reporting similar findings, these results suggest
      that heavy caffeine consumption increases the risk for fetal growth retardation.

PMID- 2003625
TI  - Does increased detection account for the rising incidence of breast cancer?
AB  - BACKGROUND: The incidence of breast cancer has been increasing over time in the
      United States. METHODS: To determine the role of screening in this increase,
      trends in the incidence of in situ and invasive carcinoma of the breast were
      evaluated using records of the metropolitan Atlanta SEER program between 1979 and
      1986. From a sample of records, evidence of symptoms and mammographic screening
      prior to diagnosis was recorded. RESULTS: The average annual age-adjusted
      incidence of invasive disease rose 29 percent among Whites and 41 percent among
      Blacks. Incidence increased in all age groups. A trend towards earlier detection
      of invasive disease was found. Asymptomatic tumors accounted for only 40 percent
      of the increased incidence among whites and 25 percent of the increased incidence
      among blacks, with mammography as the principal contributing procedure.
      CONCLUSIONS: These data suggest that increased detection accounts for some but
      not all of the rising incidence of breast cancer in the United States.

PMID- 2003626
TI  - The validity of health risk appraisals for coronary heart disease: results from a
      randomized field trial.
AB  - BACKGROUND: While health risk appraisals (HRAs) are becoming increasingly popular
      as tools for health assessment and health education, comparatively little is
      known about the accuracy of these risk estimates. METHODS: A field trial among
      732 randomly selected adults ages 25 to 65 years was conducted to assess the
      validity of the risk scores produced by four widely used HRAs. RESULTS: Self
      reported HRA risk scores for cigarette smoking and relative weight were generally
      accurate, but correlations between physiological measurements and scores for
      blood pressure, cholesterol, and physical activity were always lower than .51.
      Correlations between epidemiologic estimates of the probability of CHD death and
      HRA total risk scores ranged from .13 to .75; partial correlations adjusting for
      age, race, and gender ranged from .12 to .47. CONCLUSIONS: The HRAs chosen for
      the field trial exhibited modest correlations with the CHD mortality risk
      predicted by the epidemiologic model. Mathematical errors made by respondents
      completing self-scored instruments and lack of knowledge regarding physiologic
      status decrease the accuracy of HRA risk estimates.

PMID- 2003627
TI  - Clinical and epidemiological features of neurotoxic shellfish poisoning in North
      Carolina.
AB  - BACKGROUND: In October 1987, a red tide due to P. brevis affected the North
      Carolina coast for the first time. The purpose of our study was to describe the
      clinical and epidemiological features of neurotoxic shellfish poisoning (NSP), an
      illness caused by eating shellfish contaminated with the neurotoxins of P.
      brevis. METHODS: Active surveillance was established for cases of NSP. A
      descriptive study of the NSP cases was then completed. RESULTS: Forty-eight
      persons, who had eaten oysters at 20 meals, met the case definition. A variety of
      gastrointestinal tract and neurological symptoms were reported. The illnesses
      were generally mild and of short duration, and there were no deaths. Forty-one
      (85 percent) affected persons lived in five communities located within a 70
      kilometer area along the coast. Cases occurred from October 27 to December 9; 27
      (56 percent) of the cases occurred before the first closure of affected shellfish
      waters on November 2. There was a significant increase in the illness attack rate
      with an increase in the number of oysters eaten. CONCLUSIONS: Routine monitoring
      of coastal waters for P. brevis is needed to facilitate earlier recognition of
      red tides, closure of affected areas, and education of the public before
      substantial exposure to contaminated shellfish occurs.

PMID- 2003628
TI  - Bone cancer incidence rates in New York State: time trends and fluoridated
      drinking water.
AB  - BACKGROUND: Recent animal studies of the potential carcinogenicity of fluoride
      prompted an examination of bone cancer incidence rates. METHODS: Trends in the
      incidence of primary bone cancers, including the incidence of osteosarcomas were
      examined among residents of New York State, exclusive of New York City. Average
      annual osteosarcoma incidence rates in fluoridated and non-fluoridated areas were
      also compared. RESULTS: Among persons less than 30 years of age at diagnosis,
      bone cancer incidence among males demonstrated a significant increase since 1955,
      while incidence among females has remained unchanged. A significant decrease in
      bone cancer incidence rates since 1955 was observed among both males and females
      age 30 years and over at time of diagnosis. Osteosarcoma incidence rates have
      remained essentially unchanged since 1970, among both younger and older males and
      females. The average annual age adjusted incidence of osteosarcomas (1976-1987)
      in areas served by fluoridated water supplies was not found to differ from
      osteosarcoma incidence rates in non-fluoridated areas. CONCLUSIONS: These data do
      not support an association between fluoride in drinking water and the occurrence
      of cancer of the bone.

PMID- 2003629
TI  - Tracking progress toward national health objectives in the elderly: what do
      restricted activity days signify?
AB  - Restricted activity days is the measure by which the 1990 health objectives for
      prevention of functional disability in older adults will be evaluated. Yet its
      significance in older populations is poorly understood. We evaluated its use as
      an outcome measure for a randomized trial designed to impact upon physical
      function in elderly HMO enrollees. As predicted, restricted activity days was
      more correlated with physical disability measures than with other health status
      measures. Distributional properties and rates of missing data were shortcomings.

PMID- 2003630
TI  - Risk communication activities of state health agencies.
AB  - Surveys concerning the risk communication practices and needs of state health
      agencies were completed by agency commissioners and designated staff of 48 states
      and territories. These data indicate that agencies are expending more effort on
      responding to requests for information than on initiating dialogues with
      interested constituencies or alerting the public to risk. The data also suggest a
      gap between the stated philosophy and practice of the agencies.

PMID- 2003631
TI  - Capacity of US labs to provide TLI in support of early HIV-1 intervention.
AB  - We surveyed laboratories to assess their capacity to perform T-lymphocyte
      immunophenotyping. Of the 1026 respondents, 279 located in 41 states and the
      District of Columbia performed this type of testing. Most laboratories were
      located in hospitals, reported a low weekly test volume, and indicated that it
      took 6-24 weeks for flow cytometer operators to become proficient. Many
      laboratories appear to have the capacity to perform additional CD4+ cell testing,
      but training additional operators may be necessary. The paucity of laboratories
      performing T-lymphocyte immunophenotyping in the public sector may affect
      referral patterns from that setting.

PMID- 2003632
TI  - Response of hospitals, skilled nursing facilities, and home health agencies in
      Oregon to AIDS: reports of nursing executives.
AB  - To describe experience and readiness to provide care for persons with acquired
      immunodeficiency syndrome (AIDS), responses to a mailed survey from 86 percent of
      chief nursing executives of the 207 hospitals, skilled nursing facilities (SNFs)
      and home health agencies (HHAs) in Oregon were summarized. As of January 1989, 44
      percent reported having provided care; even in low incidence counties, 64 percent
      of hospitals had provided care. Adequate resources were reported by 79 percent in
      hospitals, 26 percent in SNFs, and 69 percent in HHAs.

PMID- 2003633
TI  - Mass flea outbreak at a child care facility: case report.
AB  - Cat fleas, Ctenocephalides felis Bouchet, were collected at a Mississippi child
      care facility after reports of large numbers of adult fleas occurring on children
      and personnel. One building yielded 161 (99 percent) of the fleas collected.
      Urticarial lesions due to flea bites occurred on the legs of six children. Flea
      presence was due to cats occupying the crawl space. Fleas were eradicated by
      eliminating entry of cats and using residual insecticides throughout the
      facility.

PMID- 2003634
TI  - Impact of work on the quality of life of community-residing young elderly.
AB  - Using a random sample of 310 Massachusetts community-residing elderly between the
      ages of 65 and 74, this study investigates the relationship between employment
      status and quality of life using a modified version of the Spitzer Uniscale QL
      index. The odds of reporting the highest quality of life rating, after
      controlling for socioeconomic and health characteristics, was 3.51:1 for those
      who worked versus those who did not do so.

PMID- 2003635
TI  - Black-white differences in cancer prevention knowledge and behavior.
AB  - Data from the 1987 National Health Interview Survey Cancer Control Supplement
      were used to estimate multivariate logistic regression models of diet change,
      mammography utilization, stool blood test utilization, and smoking. Predictor
      variables included race, sex, age, income, dietary concerns, and four knowledge
      related variables: education and three measures of cancer prevention knowledge.
      When knowledge variables were included in the models, race was not a significant
      predictor of behavior, with one exception: among women, Blacks were found to
      smoke less than Whites.

PMID- 2003636
TI  - Report of an association between race and thyroid stimulating hormone level.
AB  - We examined the association between race and thyroid stimulating hormone (TSH)
      level in 809 consecutive Black or White adults tested for mild suspicion of
      hypothyroidism with a normal TSH result. The mean TSH level of Blacks was 0.4 (SE
      .053) mU/L lower than that for Whites after age and sex adjustment, race
      explaining 6.5 percent of the variation in TSH levels. A validation sample yield
      similar results. This finding supports the possibility that differences in
      thyroid function and/or regulation may be associated with race.

PMID- 2003637
TI  - Association of waist to hip ratio and family history with the prevalence of NIDDM
      among 25,272 adult, white females.
AB  - The independent association of waist to hip ratio (WHR), relative weight, and
      family history with the prevalence of non-insulin dependent diabetes mellitus
      (NIDDM) was investigated in a population of 25,254 White females in the United
      States and Canada. A multivariate logistic analysis yielded standardized odds
      ratios of 1.47, 1.46, 1.54, and 1.14 for family history index, WHR, relative
      weight, and age, respectively.

PMID- 2003638
TI  - Healthy Cities Indiana: mainstreaming community health in the United States.

PMID- 2003639
TI  - The role of the local health department in traffic safety.

PMID- 2003640
TI  - Longevity and left-handedness.

PMID- 2003641
TI  - Congenital syphilis not an artifact.

PMID- 2003642
TI  - Lead exposure in sandblasting.

PMID- 2003643
TI  - DNA level, tumor thickness, and stereological estimates of nuclear volume in
      stage I cutaneous malignant melanomas. A comparative study with analysis of
      prognostic impact.
AB  - The mutual relation and prognostic value of three quantitative variables were
      investigated in a retrospective series of 56 stage I cutaneous malignant
      melanomas. Unbiased stereological estimates of nuclear volume, nuclear nu v were
      obtained along with measurements of melanoma thickness. The DNA index (DI) was
      determined by flow cytometry in adjacent sections from the same paraffin-embedded
      specimens. The correlation between tumor thickness and nuclear nu v was only
      moderate (r = .60). Euploid lesions had a smaller nuclear nu v than aneuploid
      tumors (2p = .01), but with considerable overlap. No significant association
      between tumor thickness and DI could be demonstrated. Single-factor analysis
      showed prognostic value of nuclear nu v and tumor thickness (2p = .0007 and 2p =
      .03, respectively), whereas DI was without prognostic impact (2p = .54). When
      analyzing the three parameters in a Cox model, nuclear nu v was the only
      independent, prognostically significant variable. Physical, three-dimensional
      nuclear volume is not solely a reflection of nuclear DNA content, and may
      represent a valuable, quantitative prognostic indicator in cutaneous malignant
      melanomas.

PMID- 2003644
TI  - Accuracy in diagnosis of lymphomatoid papulosis.
AB  - This study was undertaken to assess the accuracy of histologic diagnosis of
      lymphomatoid papulosis (LyP), which may be confused with malignant lymphoma or
      other entities. It is essential that accurate diagnoses be made because LyP may
      be a marker for malignant lymphoma. All 15 examples of LyP reviewed in a
      dermatopathology laboratory during a 14-year period and 180 histologic sections
      of tissue that could be confused with LyP were reviewed. Criteria for diagnosis
      of LyP were applied without benefit of clinical history, and revised diagnoses
      were made where indicated. Clinical follow-up information was obtained and
      original accuracy of diagnosis was assessed by comparing clinical courses with
      original histologic diagnoses. In cases of LyP in which numerous atypical
      lymphoid cells were present, 100% accuracy was noted. When fewer atypical
      lymphoid cells were present and inflammatory cell infiltrates were less dense,
      the diagnosis was less certain. Overall, a 64% correlation of clinical course and
      histologic diagnosis of LyP was noted. We conclude that the histologic diagnosis
      of LyP is generally reliable and accurate; however, in some cases a precise
      diagnosis cannot be made with certainty. Cases with fewer atypical lymphoid cells
      may fail to correlate well with the classic course of LyP and may represent a
      variant or histologic simulator.

PMID- 2003645
TI  - Disseminated superficial actinic porokeratosis. A histological review of 61 cases
      with particular reference to lymphocytic inflammation.
AB  - The pathology of 61 cases of disseminated superficial actinic porokeratosis was
      reviewed and the relative frequency of the histological features associated with
      the cornoid lamella and the pathology within and outside the porokeratotic rim
      were assessed. Papillary dermal lymphocytic infiltrate (97%), spinous layer
      vacuolar changes (90%), dyskeratotic cells in the epidermis (77%), and
      liquefaction degeneration of the basal layer (67%) were frequently seen under the
      cornoid lamella. Papillary lymphocytic infiltration was seen more frequently
      inside the porokeratotic ring in comparison to the outer skin. Lymphocyte marker
      studies in nine cases showed a predominance of activated T lymphocytes with
      positive LN3 and UCHL-1 staining. Together with the finding of a lichenoid
      reaction pattern, these results lend support to the hypothesis that actinic
      porokeratosis represents a migrating clone of abnormal keratinocytes with an
      associated immunological host response.

PMID- 2003646
TI  - Presence of melanophages in the normal Japanese skin.
AB  - Human skin samples were obtained from the normal peripheral portion of specimens
      removed from persons with various cutaneous and systemic diseases. A portion of
      each specimen was embedded in paraffin and another part in water-soluble
      embedding medium, and some was frozen in liquid nitrogen for light microscopy and
      histochemistry. Some specimens were also investigated by electron microscopy. In
      31 of 32 specimens, cells containing brown pigment were observed in the
      superficial dermis. Because both acid phosphatase and Masson-Fontana staining
      were positive and the 3,4-dihydroxyphenylalanine reaction negative, the cells
      were considered to be melanophages. Electron microscopic examination revealed
      that these cells contained melanosome-laden phagosomes. Some fibroblastlike cells
      were also observed with intracellular single or multiple melanosomes. This study
      documents the occurrence of melanophages in the normal skin of Japanese subjects.

PMID- 2003647
TI  - The histopathology of dysplastic nevi. Continued controversy.
AB  - The histopathologic criteria used in the diagnosis of dysplastic nevi have been a
      source of controversy, as has the clinical significance of these lesions. Several
      dermatopathologists noted for their work on dysplastic nevi were asked to
      contribute responses to questions regarding the architectural and cytological
      criteria used to classify a melanocytic nevus as dysplastic, the terminology used
      to describe these lesions, and the role of dysplastic nevi as precursors of
      melanoma. Although no consensus has been reached regarding the cytologic features
      required for diagnosis of dysplastic nevi, there is substantial agreement
      regarding the architectural features of these lesions.

PMID- 2003649
TI  - Malignant primitive neuroectodermal tumor presenting as a scalp nodule.
AB  - We report a case of a 20-year-old woman who presented with a 3-year history of a
      stable cystic nodule on the scalp. Light microscopy of the excised nodule
      demonstrated a malignant small round cell undifferentiated neoplasm.
      Immunohistochemical studies suggested a neural crest origin, while
      ultrastructural examination revealed characteristics of schwannian
      differentiation. Both of these special techniques were essential in establishing
      the diagnosis of a malignant epithelioid schwannoma of superficial tissue
      (neurotropic melanoma, desmoplastic melanoma). We discuss the differential
      diagnoses and describe the immunohistochemical and ultrastructural
      characteristics of this tumor. This case illustrates the difficulty of diagnosing
      this rare malignant tumor, which masqueraded as a benign-appearing scalp lesion.

PMID- 2003648
TI  - Hypo- and hyperpigmented areas in incontinentia pigmenti. Light and electron
      microscopic studies.
AB  - Incontinentia pigmenti is a rare genodermatosis typically involving three stages:
      vesiculae, verrucous lesions, and hyperpigmentation. We clinically and
      pathologically documented a case from shortly after birth until the age of 17
      years. Although the first two stages took a regular course, the third stage of
      the disease was characterized by hypopigmented streaks on the legs in addition to
      axillary hyperpigmentation. Similar hypopigmented areas were found in the
      patient's mother. Because pathological investigations of hypopigmented areas have
      been extremely rare, we performed light and electron microscopic studies and
      compared these with our findings in hyperpigmented regions. Light microscopy
      showed the hypopigmented streaks with slight epidermal atrophy and a reduced
      number of melanocytes and skin appendages. However, the main finding was round
      eosinophilic bodies in the upper dermis. Electron microscopic examination of
      these bodies demonstrated amorphous material that resembled colloid, suggesting
      degeneration of basal keratinocytes. Confirming previous reports, in
      hyperpigmented areas we found a reduction of pigment in those parts of the basal
      layer overlying melanophages located in the upper dermis.

PMID- 2003650
TI  - The rule of halves. A method of controlling the uniform "cutting-in" of skin
      biopsies.
AB  - This article describes a method of uniform gross-room sectioning of skin biopsy
      specimens, especially excisional biopsy specimens, to insure even thickness and
      maximum control of the tissue before paraffinization. This is accomplished by
      sequentially halving portions of the specimen after each cut as opposed to
      serially cutting the skin from one end to the other.

PMID- 2003651
TI  - Pure apocrine nevus. A study of light-microscopic and immunohistochemical
      features of a rare tumor.
AB  - The pure apocrine nevus is a rare tumor. A new case of pure apocrine nevi of the
      bilateral axillary regions in a 48-year-old man is herein reported. The patient
      had two soft masses of both axillae. The time of onset of the masses was unknown.
      They were not accompanied by problems of sweating. Histologically, these lesions
      comprised numerous apocrine glands extending from the reticular layer of the
      dermis to the subcutaneous tissue. In addition, sections from both of the lesions
      were stained by immunoperoxidase techniques for the presence of epithelial
      membrane antigen, carcinoembryonic antigen, and the alpha and beta subunits of
      S100 protein. Immunohistochemical features of the tumor stained by these
      antibodies are consistent with a pure proliferation of mature, well
      differentiated apocrine glands. The tumor of the present case seems to have
      developed spontaneously. It is believed, therefore, that the tumor seen in this
      patient is best categorized as a pure apocrine nevus.

PMID- 2003652
TI  - The relevance of immunohistochemical techniques in the differentiation of
      subepidermal bullous diseases.
AB  - There are several subepidermal bullous diseases. In some, the clinicopathological
      features are distinctive, whereas in others there is a variable degree of overlap
      that necessitates the use of ultrastructural and biochemical studies to
      distinguish the different diseases. In this paper, we review the literature and
      describe our experience using simplified immunological techniques in the
      diagnosis of subepidermal bullous diseases.

PMID- 2003653
TI  - The language of medicine. Words worth watching.

PMID- 2003654
TI  - Did the Spanish poet Luis de Gongora die of metastatic malignant melanoma? A
      retrospective survey on a portrait by Diego Velazquez.

PMID- 2003655
TI  - Multiple apocrine hidrocystomas on the eyelids.

PMID- 2003656
TI  - Are dermatopathologists not socially conscious?

PMID- 2003657
TI  - Dose-response evaluation of oral labetalol in patients presenting to the
      emergency department with accelerated hypertension.
AB  - STUDY OBJECTIVE: Dose-response evaluation of oral labetalol (100, 200, or 300 mg)
      on heart rate and systemic blood pressure in emergency department patients with
      hypertensive urgency (diastolic blood pressure, 110 to 140 mm Hg, and no end
      organ evidence of hypertensive emergency). METHODS: This acute-treatment, dose
      ranging study used a randomized, double-blind, parallel design. Patients with
      supine diastolic blood pressure of 110 to 140 mm Hg after 30 minutes of bedrest
      received an oral dose of labetalol. Supine blood pressure and heart rate were
      measured manually and recorded hourly for four hours after dose. Diastolic blood
      pressure of 100 mm Hg or less or a 30-mm Hg reduction in diastolic blood pressure
      was considered a treatment success. RESULTS: Two hundred fifty-five patients were
      evaluated for inclusion, and 36 patients (19 women and 17 men; mean age, 44
      years; age range, 23 to 67 years) were studied. The most frequent reason for
      exclusion was a spontaneous decrease in diastolic blood pressure to less than 110
      mm Hg (31%) with bedrest. There were 12 patients in each treatment group.
      Compared with baseline, the 100-mg dose significantly (P less than .05) reduced
      heart rate at three and four hours after dose, and the 300-mg dose significantly
      (P less than .05) reduced heart rate at one, two, and three hours after dose; the
      200-mg dose did not significantly affect heart rate. All doses produced a
      significant decrease in systolic and diastolic blood pressures at one, two,
      three, and four hours after dose compared with baseline. There were no
      statistically significant differences between treatment groups with regard to
      systolic or diastolic blood pressure or heart rate at baseline or one, two,
      three, or four hours after dose. At two hours after dose, diastolic blood
      pressure control was observed in 75%, 58%, and 67% of patients receiving 100,
      200, and 300 mg, respectively (P = .903). At four hours after dose, diastolic
      blood pressure control was observed in 50%, 64%, and 67% of patients receiving
      100, 200, and 300 mg, respectively (P = .755). A comparison of treatment success
      rates between the two time periods showed a waning of response with the 100-mg
      dose of labetalol at hour 4 compared with hour 2 (P less than .05). No adverse
      effects were observed. CONCLUSION: Labetalol provides safe and effective
      treatment for hypertensive urgencies when administered orally in doses of 100 to
      300 mg.

PMID- 2003658
TI  - Elapsed time from symptom onset and acute myocardial infarction in a community
      hospital.
AB  - STUDY OBJECTIVE: Previous reports have emphasized that thrombolytic therapy for
      acute myocardial infarction should be initiated within three or four hours of
      symptom onset to obtain the best clinical outcomes. However, our clinical
      impression was that late arrivers, who often do not receive thrombolytic therapy,
      have a good short-term prognosis. Therefore, we investigated the relationships
      among the elapsed time from symptom onset, thrombolytic therapy, and short-term
      prognosis in acute myocardial infarction patients. The research hypothesis was
      that late arrivers have a better in-hospital prognosis because they have less
      severe disease that may involve spontaneous thrombolysis. DESIGN: Observational
      cohort study based on reviewing medical records and emergency department service
      logs. SETTING: 500-bed teaching hospital with medical school affiliation in
      northeastern Ohio. TYPE OF PARTICIPANTS: Four hundred consecutive patients with
      acute infarction confirmed by chest pain and positive ECGs or elevated cardiac
      enzymes. MEASUREMENTS AND MAIN RESULTS: Patients arriving early (elapsed time
      less than or equal to 1.5 hours) were more likely to be in Killip class III or IV
      (P = .04) or to have hypotension (P = .0004); and they experienced twofold
      increased odds of ventricular tachycardia (P = .007), cardiac arrest (P = .03),
      or death (P = .01). Patients arriving late (elapsed time greater than 3.5 hours)
      were more likely to have a history of angina (P = .002) and had a better short
      term prognosis. CONCLUSIONS: Time of ED arrival after onset of acute myocardial
      infarction symptoms distinguishes two patient groups that differ in their risk of
      in-hospital complications. Late arrivers have better short-term prognoses and
      less (acutely) severe disease, and may have less need for thrombolytic therapy
      because of possible spontaneous thrombolysis. Patients with prior angina may need
      education on seeking care if their symptoms change.

PMID- 2003659
TI  - Acute pelvic inflammatory disease after surgical sterilization.
AB  - STUDY OBJECTIVE: Physicians are very cognizant of the possibility of pregnancy
      after surgical sterilization, but the potential for acute pelvic inflammatory
      disease (PID) is thought to be rare. This study was undertaken to determine if
      upper tract PID occurred more frequently than previously reported in patients
      remote from surgical sterilization. DESIGN: Retrospective review of hospitalized
      patients with the primary discharge diagnosis of PID. SETTING: Urban, university
      hospital. PARTICIPANTS: Three hundred sixty-four hospitalized patients with the
      primary discharge diagnosis of PID over a six-year study period. MEASUREMENTS AND
      MAIN RESULTS: Patients' age; gynecologic histories and diagnoses; and laboratory,
      clinical, and surgical findings were noted. Twenty-three cases of acute PID were
      identified in 21 patients previously sterilized (6%). Nine of the 23 cases had
      systemic toxicity warranting surgical evaluation; 18 of the 23 cases were
      admitted from the emergency department. Mean statistical characteristics of the
      study group were age, 27.3 +/- 0.8 (SE) years; time interval from sterilization,
      49.8 +/- 7.4 months; WBC 15,000 +/- 1,200; and temperature, 38.0 +/- 0.2 C.
      CONCLUSION: We conclude that acute PID may occur more frequently than previously
      reported in patients with prior surgical sterilization. An increased awareness of
      this entity is warranted.

PMID- 2003660
TI  - A randomized, controlled trial of the use of music during laceration repair.
AB  - STUDY OBJECTIVES: To determine whether music significantly reduces the pain and
      anxiety associated with laceration repair in the emergency department.
      PARTICIPANTS AND SETTING: Adult patients presenting to the ED at an urban
      teaching hospital for laceration repair. Exclusion criteria included patients
      less than 18 years old, having received analgesics, with suspected alcohol or
      substance intoxication, and in whom laceration repair was complicated by
      treatment of a more serious medical condition. DESIGN AND INTERVENTIONS: This was
      a randomized, controlled trial. After giving informed consent, patients were
      randomly assigned to receive standard laceration repair without music (control)
      or standard laceration repair with music. Patients assigned to the music group
      chose an audio tape from 50 available styles and artists. Patients received the
      music through a headset, and they controlled the volume. Intradermal lidocaine
      was used in all patients. Data were collected on heart rate, blood pressure, and
      respirations just before and immediately after wound repair. Psychological
      variables included the state subscale of the Spielberger State Trait Anxiety
      Inventory (STAI), a visual analog pain scale rating, and a brief questionnaire.
      STAI and pain scale ratings were analyzed with Wilcoxon's rank-sum test with an
      alpha error of .05. RESULTS: Thirty-eight patients (19 per group) completed the
      protocol. Pain scores were significantly (P less than .05) lower in the music
      group (mean, 2.09) than in controls (mean, 3.31). Anxiety after the procedure was
      reduced in both groups, but STAI reduction scores were not significantly
      different between groups (music, 17.7; control, 18.5). Seventeen of 19 patients
      (89%) rated music "very beneficial," and 100% said they would use music again.
      CONCLUSION: Music provides a safe, inexpensive, and effective adjunct for the
      management of pain in the ED but does not significantly affect anxiety.

PMID- 2003661
TI  - Outcome of CPR in a large metropolitan area--where are the survivors?
AB  - STUDY OBJECTIVES: Survival from out-of-hospital cardiac arrest in cities with
      populations of more than 1 million has not been studied adequately. This study
      was undertaken to determine the overall survival rate for Chicago and the effect
      of previously reported variables on survival, and to compare the observed
      survival rates with those previously reported. DESIGN: Consecutive prehospital
      arrest patients were studied prospectively during 1987. SETTING: The study area
      was the city of Chicago, which has more than 3 million inhabitants in 228 square
      miles. The emergency medical services system, with 55 around-the-clock ambulances
      and 550 paramedics, is single-tiered and responds to more than 200,000
      emergencies per year. TYPE OF PARTICIPANTS: We studied 3,221 victims of out-of
      hospital cardiac arrest on whom paramedics attempted resuscitation. MEASUREMENTS
      AND MAIN RESULTS: Ninety-one percent of patients were pronounced dead in
      emergency departments, 7% died in hospitals, and 2% survived to hospital
      discharge. Survival was significantly greater with bystander-witnessed arrest,
      bystander-initiated CPR, paramedic-witnessed arrest, initial rhythm of
      ventricular fibrillation, and shorter treatment intervals. CONCLUSIONS: The
      overall survival rates were significantly lower than those reported in most
      previous studies, all based on smaller communities; they were consistent with the
      rates reported in the one comparable study of a large city. The single factor
      that most likely contributed to the poor overall survival was the relatively long
      interval between collapse and defibrillation. Logistical, demographic, and other
      special characteristics of large cities may have affected the rates. To improve
      treatment of cardiac arrest in large cities and maximize the use of community
      resources, we recommend further study of comparable metropolitan areas using
      standardized terms and methodology. Detailed analysis of each component of the
      emergency medical services systems will aid in making improvements to maximize
      survival of out-of-hospital cardiac arrest.

PMID- 2003662
TI  - Dispatcher-assisted telephone CPR: common delays and time standards for delivery.
AB  - STUDY OBJECTIVES: To determine the rate of bystander CPR before and after
      implementation of a telephone CPR program in King County; to determine the
      reasons for dispatcher delays in identifying patients in cardiac arrest in
      delivering CPR instructions over the telephone; and to suggest time standards for
      delivery of the telephone CPR message. DESIGN: An ongoing cardiac arrest
      surveillance system to calculate the annual bystander CPR rates from 1976 through
      1988. Two hundred sixty-seven taped recordings of calls reporting cardiac arrests
      to nine emergency dispatch centers during 1988 were reviewed and timed. SETTING:
      King County, Washington, excluding the city of Seattle. PARTICIPANTS: Two hundred
      sixty-seven persons with out-of-hospital cardiac arrests receiving emergency
      medical services. Arrests in doctors' offices, clinics, or nursing homes were
      excluded. INTERVENTIONS: Dispatcher-assisted telephone CPR. MEASUREMENTS AND MAIN
      RESULTS: The rate of bystander CPR increased from 32% (1976 through 1981) to 54%
      (1982 through 1988) after implementation of the dispatcher-assisted telephone CPR
      program, although an increase in survival could not be demonstrated. The median
      time for dispatchers to identify the problem was 75 seconds; to deliver the early
      protocols, 19 seconds; to deliver the ventilation instructions, 25 seconds; and
      to deliver compression instructions, 30 seconds. The total time to deliver the
      entire CPR message was 2.3 minutes. The most frequent cause for delay was
      unnecessary questions (57%) with questions about patient age asked most
      frequently (32%). Other causes included the caller not being near the patient
      (29%) and deviations from protocol (22%). CONCLUSION: In a metropolitan emergency
      medical services system, a dispatcher-assisted telephone CPR program was
      associated with an increase in bystander CPR. Delays in proper delivery of
      telephone CPR can be minimized through training.

PMID- 2003663
TI  - Can nurses perform surgical cricothyrotomy with acceptable success and
      complication rates?
AB  - STUDY OBJECTIVE: This study was undertaken to determine whether flight nurses can
      perform surgical cricothyrotomies with acceptable success and complication rates.
      METHODS: This case series examined the survival, success, and complication rates
      of surgical cricothyrotomy. A specially trained flight nurse retrospectively
      reviewed all prehospital, emergency department, inpatient, autopsy, and
      outpatient follow-up records. RESULTS: Fifty-five consecutive patients in whom
      surgical cricothyrotomy was attempted by a flight nurse during a two-and-one-half
      year period were studied. Patients ranged in age from 9 to 76 years. The airway
      was not cannulated successfully by a flight nurse in two patients. In two
      patients, the tube was not in the cricothyroid space (one in the upper tracheal
      rings, and the other in the larynx). In three patients, packing was insufficient
      to stop bleeding from around the operative site; and in three the tube became
      occluded by blood in the emergency department. Finally, two patients developed
      subglottic stenosis. CONCLUSION: Surgical cricothyrotomy in the field can be
      performed reliably by specially trained nurses. Because only the most critically
      ill or injured patients with unmanageable airways are subjected to this
      procedure, a significant complication rate can be anticipated.

PMID- 2003664
TI  - A prehospital model of intraosseous infusion.
AB  - STUDY OBJECTIVE: Before the implementation of an intraosseous infusion protocol
      by the City of Pittsburgh paramedics, we undertook a study to compare the
      establishment of a simulated intraosseous infusion in three different prehospital
      settings. The purpose of this study was to determine the time to establish an
      intraosseous infusion and the success rate at the scene and en route to the
      hospital using this model. DESIGN: Prospective study. SETTING: Three prehospital
      scenarios: classroom (scene); a medic unit traveling at 25 mph and making slow,
      steady turns (turns); and a medic unit traveling at 30 to 35 mph with sudden
      stops and starts (stop and go). TYPE OF PARTICIPANTS: Paramedics and emergency
      medicine residents. MEASUREMENTS AND MAIN RESULTS: Successful placement of the IO
      needle was confirmed by the aspiration of marrow or the free flow of 5 to 10 mL
      of normal saline without extravasation into the surrounding tissue. The procedure
      was timed from skin entry to establishment of infusion. All participants were
      successful in establishing IO infusion, with 84.8% of infusions achieved in less
      than one minute in all settings. The scene had somewhat shorter mean and median
      times and a higher first-attempt success rate, but the differences between
      scenarios were not significant. CONCLUSION: Using a simulated model, IO access
      can be established successfully in the prehospital setting. The minimal time
      delay in establishing IO infusion may make it an appropriate technique for use at
      the scene or en route to the hospital.

PMID- 2003665
TI  - Glucagon: prehospital therapy for hypoglycemia.
AB  - STUDY OBJECTIVE: This study evaluated the efficacy of glucagon for prehospital
      therapy of hypoglycemia in patients without IV access. DESIGN: Prospective
      clinical trial. SETTING: Prehospital in a busy, urban emergency medical services
      system. TYPE OF PARTICIPANTS: Fifty consecutive patients presenting with
      documented hypoglycemia (ChemStrip BG less than or equal to 80 mg/dL) and
      symptoms of decreased level of consciousness, syncope, or seizure were enrolled.
      MEASURES AND MAIN RESULTS: Data collected included pretreatment (ChemStrip BG)
      and post-treatment serum glucose (hospital assay) as well as assessment of level
      of consciousness by a quantitative measure, the Glasgow Coma Score, and by a
      qualitative scale (0 to 3). The mean pretreatment blood glucose of 33.2 +/- 23.3
      mg/dL increased after treatment to 133.3 +/- 57.3 mg/dL. Qualitative level of
      consciousness increased from a mean of 1.26 +/- .96 to 2.42 +/- .94 and Glasgow
      Coma Score increased from a mean of 9.0 +/- 4.19 to 13.04 +/- 3.68. The mean time
      until response was 8.8 minutes in those who responded to both level of
      consciousness criteria 82% (41 of 50). Glucagon administered for hypoglycemia
      resulted in a glucose increase in 98% (49 of 50) with headache as the only side
      effect noted in 4% (two of 50) of patients (P less than .0001). CONCLUSION:
      Glucagon is safe and effective therapy for hypoglycemia in the prehospital
      setting.

PMID- 2003666
TI  - Efficacy of computer-assisted instruction in the continuing education of
      paramedics.
AB  - STUDY OBJECTIVE: To determine the relative effectiveness of lecture, video, and
      computer-assisted instruction (CAI) for the continuing education of paramedics.
      DESIGN: The study was a statewide, cross-sectional, and prospective. It used
      premethod, post method and 60-day evaluations addressing both cognitive knowledge
      and attitude toward the method. Subjects were required to complete a 20-question
      cognitive examination and a ten-point satisfaction inventory. Each study site was
      randomly assigned a method by a computer-generated table. SETTING: The study
      involved 11 sites, systematically distributed throughout Michigan. TYPE OF
      PARTICIPANTS: 111 Michigan licensed paramedics. RESULTS: CAI subjects scored an
      average of 79.6% on the post-test, while lecture and video subjects scored 70.5%
      and 68.9%, respectively. At 60 days, CAI subjects scored 70.9%, while lecture and
      video subjects averaged 59.4 and 59.1, respectively. The difference among the
      scores was significant post method (P = .01) and at 60 days (P = .02). The
      subject method preference was lecture, video, and CAI premethod; lecture, CAI,
      and video immediately post method; and lecture, CAI, and video at 60 days.
      CONCLUSION: Although lecture was the preferred method, CAI was best able to
      impart knowledge and enhance participant knowledge retention.

PMID- 2003667
TI  - Level of medical care required for mass gatherings: the XV Winter Olympic Games
      in Calgary, Canada.
AB  - STUDY OBJECTIVE: To determine the level of medical care required for mass
      gatherings and describe the types of medical problems encountered in a major
      winter event. DESIGN: Standard charts were available for 3,395 encounters.
      Interviews with medical staff showed that the few unrecorded encounters were for
      very minor medical problems. A four-tiered triage system (low, moderate, urgent,
      and emergent) developed before the Games was applied to each chart
      retrospectively by a single emergency physician. Chi-squared tests were used to
      test significant differences. SETTING: This winter sporting and entertainment
      event had 12 urban and rural venues. Medical staff (98 physicians, 161 nurses,
      and 337 first-aid attendants) were based in 28 advanced life support (ALS)
      clinics. The medical service operated for four weeks. TYPE OF PARTICIPANTS: There
      were 1.8 million spectator-days. Patients included spectators, athletes, and
      support staff. INTERVENTIONS: First-aid attendants referred patients to the
      clinics, where nurses conducted initial assessments and referred patients to
      physicians at the venue, or more rarely, to local hospital emergency departments.
      Paramedic ambulances were stationed at the venues. The triage system was not used
      for patient management. MEASUREMENTS AND MAIN RESULTS: Only 40 urgent and one
      emergent medical problems were encountered. The majority of patients could have
      been managed by trained nurses working alone under standing orders. Fifty
      patients were transported to the hospital by ground ambulance and three by
      helicopter. No significant differences were found in the low acuity levels
      experienced at indoor urban venues, outdoor urban venues, and the rural cross
      country ski venue. The Alpine ski venue was characterized by significantly higher
      acuity and a long prehospital transfer phase. CONCLUSION: Owing to the low acuity
      encountered and the availability of Calgary's ALS ambulance service, we concluded
      that physician-based ALS teams were not required for patient management at the
      urban venues. Such teams were found to be required at the rural Alpine ski venue.
      Other reasons for using physicians are discussed, as is development of a standard
      triage system for mass gatherings.

PMID- 2003668
TI  - The St Croix disaster and the National Disaster Medical System.
AB  - The National Disaster Medical System was designed to respond to a catastrophic
      disaster by creating a group of specially trained civilian disaster medical
      assistance teams. The teams would be transported to the periphery of the event to
      triage, stabilize, and then prepare victims for evacuation to facilities
      elsewhere in the United States that have agreed in advance to accept such
      patients. Hurricane Hugo's devastation in St Croix offered the first opportunity
      to test the system. The event was an example of a type of medical disaster that
      resulted in a sudden reduction in medical resources without a great increase in
      casualties. Background information and operation of the New Mexico disaster
      medical assistance team are presented with a clinical profile of the patients
      seen during the disaster. We describe the first actual deployment of a disaster
      medical assistance team and the issues that must be addressed before future
      deployments.

PMID- 2003669
TI  - Thrombolytic therapy for noncoronary diseases.
AB  - Thrombolytic therapy has been used fairly extensively in the management of acute
      proximal deep-vein thrombophlebitis of the extremities, acute pulmonary embolism,
      and acute peripheral arterial thrombosis and embolism in addition to acute
      thrombotic coronary events. In the presence of acceptable indications and a
      favorable benefit to risk ratio, this form of therapy, when successful, has
      served as a useful adjunct in the management of these disorders. In deep-vein
      thrombophlebitis, lysis of the thrombus before permanent pathological changes
      (eg, organization, scarring) have occurred can prevent venous valvular
      dysfunction and postural venous hypertension and its complications, especially
      the postphlebitic syndrome. In the more severe forms of acute pulmonary embolism,
      thrombolytic therapy, when applied early after symptom onset, decreases morbidity
      and is likely to prevent a chronic increase in pulmonary vascular resistance and
      persistent pulmonary hypertension. In peripheral arterial thrombo-occlusive
      events, early restoration of flow through thrombolysis has been shown to limit
      ischemic damage and serve as a useful supplement to angioplasty or surgery.
      Thrombolytic therapy has been used less extensively in acute strokes. Here the
      danger of reperfusion causing bleeding into a softened area of brain undergoing
      infarction has slowed its evaluation for this disorder; its application to stroke
      remains experimental.

PMID- 2003670
TI  - Endocarditis in the emergency department.
AB  - Clinical presentations and pathogeneses of endocarditis and aspects of its
      diagnosis and management relevant to emergency department practice are reviewed.
      Guidelines for admission, laboratory evaluation, and decisions regarding the
      initiation of therapy in the ED are offered. Also discussed are the role of the
      emergency physician in the prevention of iatrogenic infection and current
      recommendations regarding administration of prophylactic antibiotics for ED
      procedures.

PMID- 2003671
TI  - Delayed presentation of intrapericardial diaphragmatic hernia, an unusual cause
      of colon obstruction.
AB  - The earliest symptoms of diaphragmatic hernia may not appear until viscera
      incarcerate in it years after the causal injury. The most unusual site for a
      diaphragmatic hernia to occur is through the central tendon of the diaphragm into
      the pericardium. We present the case of a 43-year-old man who suffered a bowel
      obstruction when the transverse colon and omentum became incarcerated in the
      intrapericardial diaphragmatic hernia. The defect presumably resulted from blunt
      chest and abdominal trauma received 15 years earlier. The delayed presentation of
      intrapericardial diaphragmatic hernia is reviewed, and recommendations for
      evaluation and treatment are made.

PMID- 2003672
TI  - Attack of the sand brier.
AB  - Corneal foreign bodies represent one of the more common sources of eye-related
      trauma presenting to emergency and primary care physicians. Presented is the case
      of a man in whom the diagnosis was overlooked because a magnifying optical device
      was not used.

PMID- 2003673
TI  - Pyogenic hepatic abscess.
AB  - Presented is a case of spontaneous pyogenic hepatic abscess in a previously
      healthy young man without associated risk factors. This disease entity has a low
      incidence, however, it is associated with significant morbidity and mortality if
      diagnosis and treatment are delayed.

PMID- 2003674
TI  - Spontaneous rupture of the spleen in initial presentation of Hodgkin's disease.
AB  - A 46-year-old man presented with a four-week history of fevers, occasional
      chills, and a two-week history of sweats and poor appetite. He also complained of
      progressive weakness and lethargy. After initial evaluation, while awaiting
      further consultation, the patient developed rapidly progressing abdominal pain
      and light-headedness. He was moved immediately into the emergency treatment area.
      He was noted to have an acute abdomen and was taken to surgery. An enlarged
      Hodgkin's-infiltrated spleen with an actively bleeding hematoma was removed. The
      patient denied any history of trauma.

PMID- 2003675
TI  - Prehospital care: the future of emergency medical services.
AB  - Most prehospital interventions, both pharmacologic and procedural, have been
      accepted without clear demonstrations of their abilities to impact patient
      outcomes or without clear indications that withholding or delaying the
      intervention pending arrival at a definitive emergency department will adversely
      affect the patient. Interventions that have the benefit of supportive research
      have been applied equally to urban and nonurban emergency medical services
      environments. In selecting interventions, inadequate consideration has been given
      to the differences in emergency medical services personnel training, frequencies
      of their exposure to patients, frequencies of skill use, and availabilities of
      effective continuing education programs in the urban and nonurban environments.
      These issues are discussed, and the necessary focus of the future of emergency
      medical services in urban, suburban, and rural environments is predicted.

PMID- 2003676
TI  - Model curriculum in air medical transport for emergency medicine residencies.

PMID- 2003677
TI  - Meaningful response time interval: is it an elusive dream?

PMID- 2003678
TI  - Radiographs in the diagnosis of epiglottitis.

PMID- 2003679
TI  - Closed thoracic cavity lavage for hypothermia with cardiac arrest.

PMID- 2003680
TI  - Verifying dose response.

PMID- 2003681
TI  - Abstracts of the 21st annual meeting of the Society for Academic Emergency
      Medicine. Washington, DC, May 12-15, 1991.

PMID- 2003682
TI  - Control of human airway smooth muscle.

PMID- 2003683
TI  - Mechanical properties of sensitized airway smooth muscle. Shortening capacity.

PMID- 2003684
TI  - Nonadrenergic inhibitory nervous systems in the airways.

PMID- 2003685
TI  - Neural control of airway vasculature and edema.
AB  - The tracheobronchial vasculature is controlled by adrenergic, cholinergic, and
      peptidergic nervous mechanisms. Sympathetic nerves release norepinephrine and
      neuropeptide Y (NPY), which are both constrictor agents, the latter being long
      lasting. Parasympathetic nerves release acetylcholine and usually vasoactive
      intestinal polypeptide (VIP), both of which are vasodilators, VIP being the
      longer lasting. These motor nerves are controlled by many reflex inputs.
      Activation of pulmonary C-fiber receptors by irritants and inflammatory mediators
      causes a powerful vasodilatation, mainly via sympathetic motor nerves. Cardiac
      and chemoreceptor reflexes also influence airway vascular tone. Sensory nerves in
      the airway mucosa are responsible for local axon reflexes in response to
      irritants and inflammatory mediators. These nerves contain neuropeptides such as
      substance P (SP), neurokinins A and B (NKA, NKB), and calcitonin gene-related
      peptide (CGRP). All these neuropeptides are powerful vasodilators. Thus,
      inflammatory conditions in the lungs such as asthma cause vasodilation by local
      direct action of mediators, by axon reflexes, and by central nervous reflexes.
      The vasodilation could lead to mucosal edema. Thus, airway vascular responses
      have to be added to bronchoconstriction and mucus secretion as part of the
      mucosal pathology of asthma.

PMID- 2003686
TI  - Effect of inflammatory mediators on airway nerves and muscle.
AB  - The neuromuscular mechanisms underlying airway hyperresponsiveness have been
      reviewed on the basis of studies of the changes induced by ozone inhalation in
      dogs. In vivo, there is increased, nonspecific airway hyperresponsiveness based
      on studies of the response to inhaled acetylcholine or histamine. The underlying
      inflammatory mechanism involves release of LTB4 and/or other chemotactic agents
      from epithelial or lumenal cells, ingress of macrophages, neutrophils, and
      platelets from the blood vessels between the muscle and epithelium, and migration
      of mast cells into the epithelium. The hyperresponsiveness seems to depend upon
      the influx of neutrophils and actions of thromboxane A2 released from the
      neutrophils. In vitro, there is increased responsiveness to field stimulation of
      cholinergic nerves and to acetylcholine (not to KCI) in tracheal strips. These
      effects can be mimicked by a thromboxane A2 analog (U44619). In the sucrose gap,
      the TxA2 analog does not affect the excitatory junction potential, but in low
      concentration it increases and prolongs a series of fading membrane oscillations
      closely related to the contractions. We consider these oscillations to reflect
      ongoing release and/or action of acetylcholine. In high concentrations the analog
      causes a small depolarization and a tonic contraction, but it does not enhance
      the sensitivity to acetylcholine. TxA2 may be acting either presynaptically or
      postsynaptically or both to produce these effects; however, changes in release of
      an epithelial-derived relaxing factor do not seem to be involved. We conclude
      that TxA2 actions probably underlie hyperresponsiveness developed in vivo and in
      vitro after ozone inhalation.

PMID- 2003687
TI  - Modulation of neurogenic inflammation by neutral endopeptidase.
AB  - The enzyme neutral endopeptidase (NEP) is bound to the membranes of selected
      cells in the airways that have receptors for tachykinins. The location of the
      enzyme, along with its selectivity of substrates (tachykinins are a preferred
      substrate), allows the enzyme to cleave tachykinins that come close to the cell
      surface receptors. By cleaving and thus inactivating tachykinins released during
      stimulation of the sensory nerves, NEP limits the degree of neurogenic
      inflammation. Neutral endopeptidase exists in the basal cells of the airway
      epithelium, nerves, smooth muscle, glands, blood vessels, and perhaps other
      cells. Thus, the enzyme modulates smooth muscle contraction, gland secretion,
      cough, vascular permeability, and neutrophil adhesion. Decreased NEP activity
      occurs with epithelial removal, during respiratory viral infections, and during
      exposure to irritants (e.g., cigarette smoke and toluene diisocyanate). Delivery
      of recombinant NEP (rNEP) by aerosol suppressed cough responses during neurogenic
      inflammation. We suggest that decreased NEP activity will result in exaggerated
      neurogenic inflammation and may play an important role in inflammatory diseases
      in airways. Furthermore, drugs that cause up-regulation of NEP may play a
      therapeutic role by suppressing neurogenic responses. Replacement therapy with
      rNEP may be useful in diseases where inflammatory peptides (e.g., tachykinins,
      bradykinin) play a role in pathogenesis.

PMID- 2003688
TI  - Evidence for inflammation in asthma.

PMID- 2003689
TI  - Factors determining bronchial smooth muscle shortening.

PMID- 2003690
TI  - Site of airway hyperreactivity.

PMID- 2003691
TI  - Airway luminal liquid. Sources and role as an amplifier of bronchoconstriction.
AB  - The release of mediators from inflammatory cells into the airway lumen can
      initiate a series of events leading to airway obstruction, particularly smooth
      muscle contraction and alteration of endothelial and epithelial permeability
      leading to mucosal edema and subsequent influx of liquid into the airway lumen.
      In this report we briefly review the effects of several inflammatory mediators,
      including eicosanoids, platelet-activating factor, and histamine, as well as the
      effects of plasma proteins and tachykinins that may be secondarily released
      because of the presence of inflammatory mediators on endothelial and epithelial
      permeability. We then consider physical mechanisms whereby the resulting airway
      luminal liquid could amplify the response of an airway previously constricted
      because of smooth muscle contraction. Specifically, liquid in the interstices
      between epithelial projections that are formed during muscular contraction could
      amplify the degree of luminal compromise by (1) further decreasing luminal cross
      sectional area by occupying space, and (2) providing an additional source of
      inward recoil because of the surface tension of the air-liquid interface.

PMID- 2003692
TI  - Mast cell/nerve interactions in vitro and in vivo.
AB  - In this report, we review the evidence for mast cell/nerve interactions. We
      believe that the morphologic and functional evidence now strongly support a
      purposeful and biologically significant interaction between these two cell types.
      This interaction has physiologic consequences and appears to be able to regulate
      such local events as chloride ion secretion by epithelial cells of the intestinal
      and respiratory tracts in experimental models. In this way, the mast cell and
      nerve may be considered as a functional homeostatic regulatory unit. The extent
      to which this unit may be involved in maintenance of normal integrity of mucous
      membranes or other structures, in health and in disease, is not clear at the
      present and will require considerably more investigation and elucidation.
      However, the concept of such an interaction is an interesting one and may bring
      new approaches of a therapeutic and diagnostic nature to bear on some old
      problems. The observations reviewed in this report that psychologic conditioning
      may itself cause mucosal mast cell degranulation and mediator release in the rat
      is significant. We consider that this evidence of central nervous system control
      of mast cell degranulation is an extension of the idea that mast cells and nerves
      communicate.

PMID- 2003693
TI  - Granulocytes and airway reactivity.

PMID- 2003694
TI  - The role of the eosinophil in asthma.

PMID- 2003695
TI  - Effect of pregnancy on airway responsiveness and asthma severity. Relationship to
      serum progesterone.

PMID- 2003696
TI  - PAF antagonism as an approach to the treatment of airway hyperreactivity.
AB  - Platelet-activating factor (PAF) would seem a good candidate for a mediator of
      airway hyperreactivity. It has been reported to induce a long-lasting, if modest,
      increase in hyperreactivity in both experimental animals and humans. Evidence
      (albeit often indirect) suggests increased levels associated with bronchial
      hyperreactivity or the related "late-phase reaction" of asthma. In experimental
      animals, specific inhibitors of PAF can suppress both allergen and PAF-induced
      hyperreactivity as well as the late-phase reaction to allergen. The mechanism by
      which PAF induces hyperreactivity is unknown, but the potent effects of PAF on
      the eosinophil, a cell characteristic of the inflammatory processes often
      associated with asthma and hyperreactivity, may be important. A number of potent
      and selective PAF antagonists are now available. The crucial test for the
      hypothesis that PAF has a role in human airway hyperreactivity will be the
      testing of substances such as these in appropriate double-blind, placebo
      controlled clinical trials.

PMID- 2003697
TI  - Bilaminate synthetic dressing for partial thickness burns. Lack of cost reduction
      for inpatient care.
AB  - Forty-nine cases of second degree burns initially treated as inpatients from
      April 1984 through December 1987 are reviewed. Thirty-four patients were treated
      with bilaminate synthetic dressing (Biobrane) application, while 15 were treated
      with a topical antimicrobial, usually silver sulfadiazine. The burns ranged from
      1 to 25 per cent total body surface area and were comparable in both groups. The
      mean age in each group was 30 years. Thirty patients were successfully treated
      with Biobrane, and their average hospital stay was 9.1 +/- 5.4 days compared with
      9.2 +/- 8.6 days for the topically treated group. The mean hospital cost for
      dressings and supplies for the Biobrane group was $360 +/- $90 compared with $310
      +/- $190 for the topical group. Four patients (12%) required Biobrane removal
      during their hospitalization, one due to increasing burn depth and three due to
      purulent fluid collections beneath the Biobrane. These burns were subsequently
      treated with topical antimicrobial agents and healed primarily. The mean total
      hospital stay for this group was 18.0 +/- 11.9 days with the costs being much
      higher secondary to the initial cost of the Biobrane, the costs associated with
      topical antibiotic therapy, and extended hospital stay. Although there was a
      decrease in nursing time and a subjective decrease in patient discomfort
      associated with using synthetic dressing, no benefit was found in either
      decreasing hospital stay or total cost of hospitalization and supplies used for
      inpatients treated at this institution.

PMID- 2003698
TI  - Endoscopic laser surgery. A single-center comprehensive experience.
AB  - A retrospective review of endoscopic procedures using the Nd:YAG laser was
      carried out for patients treated between October 1985 and March 1989. During this
      42-month period 165 procedures were performed on 100 patients. The study
      encompasses a unique period of time in this center, as it includes the initial
      application, and finally, the time when its use became routine. Indications for
      laser surgery included the treatment of tumors, bleeding, benign strictures,
      arterial occlusions, and hemorrhoids. Nd:YAG laser was found to be effective in
      the treatment of these lesions. The overall success rate was 81 per cent.
      Patients who are poor surgical candidates would especially benefit from this
      therapeutic alternative.

PMID- 2003699
TI  - Preperitoneal herniorrhaphy for the acutely incarcerated groin hernia.
AB  - Elective preperitoneal or posterior repair for recurrent groin hernias and
      primary femoral hernias has been shown to be a technically advantageous approach.
      In addition to the ease of inguinal floor and femoral canal assessment, scar
      tissue from prior anterior herniorrhaphy can be avoided. The emergency management
      of the acutely incarcerated or strangulated hernia of the groin using this
      approach has not been addressed. During a 30-month period, all patients with a
      diagnosis of acute incarceration of a groin hernia (n = 28) were surgically
      managed using either the anterior approach (AA) (n = 14) or the preperitoneal
      approach (PA) (n = 14). Two patients with strangulated intestine in the AA group
      required an additional midline incision for bowel evaluation and resection.
      Intestinal evaluation was easily accomplished through the same incision in four
      patients in the PA group. The preperitoneal approach also allowed proximal
      control of incarcerated or strangulated viscera, thus avoiding excessive
      manipulation of gangrenous or necrotic intestine, potential spillage of infected
      contents into the peritoneal cavity, and entry of bacteria, toxins, potassium,
      and the metabolic waste products of anaerobic metabolism into the systemic
      circulation during hernia reduction. There have been no recurrences in either
      group, and minor complications, such as wound infection and cellulitis, in the
      two groups are not statistically different.

PMID- 2003700
TI  - Is primary repair of gastroschisis and omphalocele always the best operation?
AB  - Optimal surgical management of neonates with gastroschisis and omphalocele
      remains controversial. Suggested benefits of primary fascial closure include
      earlier return of gastrointestinal function, decreased hospital stay, less
      sepsis, less risk of postoperative intestinal obstruction and fistulae, and lower
      mortality. Between 1978 and 1989, 40 neonates with gastroschisis or omphalocele
      underwent repair. Primary fascial repair was performed in 30 children, 18 of whom
      had a gastroschisis and 12 of whom had an omphalocele. Ten children had staged
      repair with the use of a silastic silo; seven of these had a gastroschisis and
      three an omphalocele. Comparison between the groups was made regarding birth
      weight, days on the ventilator before and after surgery, days to first feeding,
      days in the hospital after surgery, postoperative complications, and survival.
      There was no significant difference in birth weight, days on the ventilator, days
      to first feeding, and postoperative days in the hospital. There were nine
      complications in nine patients (30%) with primary repair and four complications
      in two patients (20%) with staged repair. Two infants died after primary repair
      (6.7%), and one (10%) died after staged closure. It was concluded that silastic
      silo repair and primary fascial closure are both acceptable alternatives. Primary
      closure is attractive whenever possible to avoid additional operations.

PMID- 2003701
TI  - Volvulus of the colon.
AB  - The charts of all patients with colonic volvulus at the University of Louisville
      Hospitals between 1983 and 1988 were reviewed. A total of 45 patients were
      identified, and there were 17 with cecal volvulus and 29 with sigmoid volvulus (1
      had both). Two-thirds of the patients were either demented, bedridden, or used
      constipating drugs. Initial nonoperative decompression was achieved in 26 of 29
      patients with sigmoid volvulus but in only three of nine patients in which it was
      attempted with cecal volvulus. Two of these recurred, and 16 of the 17 cecal
      volvulus patients underwent operation. One-third of the sigmoid volvulus patients
      had at least one recurrent episode on the index admission. Fourteen of the 29 had
      an operation, and half of these patients died following surgery. Fifteen sigmoid
      volvulus patients chosen to be treated with successive nonoperative treatment had
      no mortality. Mortality was higher following emergent (4 of 5) than elective (2
      of 9) operation for sigmoid volvulus, and one of three died after operation for a
      successfully decompressed first episode. Mortality for nonoperative reduction of
      an early recurrence was zero of four patients, while operative mortality for
      recurrence was two of seven (all had successful preoperative deflation). There
      was no mortality or recurrence in four patients with cecal volvulus treated by
      cecopexy alone, but all three patients died in whom tube cecostomy was performed.
      Two of nine patients died following right hemicolectomy. These data suggest that
      if an elective operation is to be performed for sigmoid volvulus, it should be
      done following one or more recurrences and that nonoperative decompression can be
      safely performed on successive occasions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 2003702
TI  - Spontaneous pneumoperitoneum. A surgical dilemma.
AB  - Pneumoperitoneum is usually the result of hollow viscus perforation with
      associated peritonitis. Nonsurgical spontaneous pneumoperitoneum incidental to
      intrathoracic, intra-abdominal, gynecologic, iatrogenic, and other miscellaneous
      causes not associated with perforated viscus have been documented in the
      literature. Seven cases of spontaneous pneumoperitoneum admitted over 3-year
      period to Grady Memorial Hospital, Atlanta, Georgia are reported. Six patients
      with pneumoperitoneum underwent exploratory laparotomy when clinical examination
      suggested an acute abdomen; no intra-abdominal pathology was documented in any of
      these patients. A seventh patient, on ventilatory support, was managed
      conservatively after performing a diagnostic peritoneal lavage that was negative.
      There were no cases of radiographically misdiagnosed pneumoperitoneum.
      Pneumoperitoneum, preceded by a reasonable incidental cause in a patient with a
      adequate abdominal examination, may warrant continued observation thus avoiding
      an unnecessary laparotomy.

PMID- 2003703
TI  - Tracheoplasty for congenital long-segment intrathoracic tracheal stenosis.
AB  - Congenital long-segment intrathoracic tracheal stenosis (CTS) is a rare life
      threatening obstruction in infancy and childhood. From July 1983 to March 1988
      six infants aged 14 days to 14 months with CTS were identified. Symptoms ranged
      from recurrent stridor and wheezing to severe respiratory compromise and
      hypercarbia. Routine chest x-rays were not diagnostic. Definitive diagnosis was
      made by bronchoscopy, which showed complete tracheal rings in all patients with
      severely compromised tracheobronchial lumens. In three patients, pericardium was
      successfully used for anterior tracheoplasty with one early death due to
      fulminant sepsis in an infant with undiagnosed sickle cell disease. The other two
      died late, at 3 and 9 months from problems unrelated to the repair. In three
      patients a rib graft was used for repair; in one, tracheoplasty was required
      after earlier repair of tetralogy of Fallot. All are late survivors with no
      postoperative symptoms. After recognition of CTS, prompt surgery is warranted to
      avoid the late complications of tracheostomy for long-term ventilatory support.
      Rigid repair with rib cartilage is preferable to use of pericardium. Proper rib
      harvesting with intact perichondrium, intraoperative bronchoscopy, oxygenation by
      cardiopulmonary bypass, and meticulous graft alignment are necessary for
      successful postoperative outcome.

PMID- 2003704
TI  - The failure of serial pneumatic cuff venous occlusion plethysmography to predict
      patients at risk for pulmonary emboli after trauma.
AB  - Over a three month period, attempts to perform serial Pneumatic Cuff Venous
      Occlusion Plethysmography (VP) were carried out in 51 severely injured patients
      felt to be at risk for Pulmonary Embolus (PE). Studies could not be performed in
      25 of these patients due to the nature of their injuries. Of the remaining 26
      patients, two showed evidence of deep vein thrombosis (DVT). Venography confirmed
      the diagnosis in only one of these patients. Serial VP failed to predict PE in
      all five patients in whom it was diagnosed. This article concludes that serial VP
      is not an effective predictor of PE in these patients.

PMID- 2003705
TI  - Colonoscoping the "difficult" colon.
AB  - Despite the popularity of colonoscopy, very little has been published on specific
      technique. There are many factors that make colonoscopy easy or difficult, but
      the most important one is the endoscopist himself/herself. One must have
      excellent manual dexterity and technical ability; and, above all, one must
      perform enough cases to gain the needed experience to understand the procedure
      and to perform it rapidly, successfully, and safely. There are only so many
      maneuvers that can be carried out with a colonoscope, such as pushing it in,
      withdrawing it, turning it to the right, left, up, or down. Therefore, decision
      making (options), such as changing the position of the patient or applying
      external pressure points, must be performed rapidly before too many repetitive
      false moves are made. Options for each anatomical segment of the colon are
      outlined, based on an experience of ten thousand colonoscopies.

PMID- 2003706
TI  - Effect of antihypertensives on sexual function and quality of life: the TAIM
      Study.
AB  - OBJECTIVE: To evaluate treatment of mild hypertension using combinations of diet
      and low-dose pharmacologic therapies. DESIGN: Multicenter, randomized, placebo
      controlled clinical trial. SETTING: Three university-based tertiary care centers.
      PATIENTS: Patients (697) 21 to 65 years of age with diastolic blood pressure
      between 90 and 100 mm Hg as well as weight between 110% and 160% of ideal weight.
      INTERVENTION: Patients were stratified by clinical center and race and were
      randomly assigned to one of three diets (usual, low-sodium and high-potassium,
      weight loss) and one of three agents (placebo, chlorthalidone, and atenolol).
      MEASUREMENTS: Changes in measures of sexual problems, distress, and well-being
      after 6 months of therapy were analyzed. MAIN RESULTS: Low-dose chlorthalidone
      and atenolol produced few side effects, except in men. Erection-related problems
      worsened in 28% (95% CI, 15% to 41%) of men receiving chlorthalidone and usual
      diet compared with 3% (CI, 0% to 9%) of those receiving placebo and usual diet (P
      = 0.009) and 11% (CI, 2% to 20%) of those receiving atenolol and usual diet (P
      greater than 0.05). The weight loss diet ameliorated this effect. The low-sodium
      diet with placebo was associated with greater fatigue (34%; CI, 23% to 45%) than
      was either usual diet (18%; CI, 10% to 27%; P = 0.04) or weight reduction (15%;
      CI, 7% to 23%; P = 0.009). The low-sodium diet with chlorthalidone increased
      problems with sleep (32%; CI, 22% to 42%) compared with chlorthalidone and usual
      diet (16%; CI, 8% to 24%; P = 0.04). The weight loss diet benefited quality of
      life most, reducing total physical complaints (P less than 0.001) and increasing
      satisfaction with health (P less than 0.001). Total physical complaints decreased
      in 57% to 76% of patients depending on drug and diet group, and were markedly
      decreased by weight loss. CONCLUSION: In general, low-dose antihypertensive drug
      therapy (with chlorthalidone or atenolol) improves rather than impairs the
      quality of life; however, chlorthalidone with usual diet increases sexual
      problems in men.

PMID- 2003707
TI  - Quality-of-life-adjusted evaluation of adjuvant therapies for operable breast
      cancer. The International Breast Cancer Study Group.
AB  - OBJECTIVE: To evaluate a single cycle of adjuvant chemotherapy compared with
      longer duration chemotherapy for premenopausal women or chemoendocrine therapy
      for postmenopausal women with operable breast cancer using a quality-of-life
      oriented end point, Q-TWiST (quality-adjusted analysis of TWiST: Time Without
      Symptoms and Toxicity). DESIGN: Multicenter randomized clinical trial-
      International Breast Cancer Study Group (IBCSG: formerly Ludwig Group) Trial V.
      SETTING: IBCSG participating centers in Sweden, Switzerland, Australia,
      Yugoslavia, Spain, New Zealand, Italy, Germany, and South Africa. PATIENTS: Data
      were available for 1229 eligible patients with node-positive breast cancer who
      were randomized to receive one of three adjuvant treatments after at least a
      total mastectomy and axillary clearance. INTERVENTIONS: Patients received either
      a single cycle of perioperative chemotherapy consisting of cyclophosphamide,
      methotrexate, fluorouracil, and leucovorin; or six cycles (6 months) of a
      conventionally timed chemotherapy consisting of cyclophosphamide, methotrexate,
      fluorouracil, and prednisone for premenopausal women or this combination plus
      tamoxifen for postmenopausal women; or both perioperative and conventionally
      timed chemotherapy for a 7-month course of adjuvant therapy. RESULTS: At 5 years
      of median follow-up, patients who received the longer duration therapies had an
      improved 5-year disease-free survival percentage (53% compared with 36%; P less
      than 0.001) and 5-year overall survival percentage (73% compared with 63%; P =
      0.001) compared with those who received the single perioperative cycle alone. By
      3.5 years, the greater burden of toxic effects associated with the longer
      duration treatments was balanced by their superior control of disease. Within 5
      years of follow-up, even after subtracting time with adjuvant treatment toxicity,
      patients gained an average of 2.2 months of Q-TWiST if treated with the longer
      duration therapies compared with the single cycle (P = 0.03). The gain for
      premenopausal patients was 2.8 months (P = 0.05), whereas the gain for
      postmenopausal women was 1.5 months (P greater than 0.2). CONCLUSIONS: Six or
      seven months of adjuvant chemotherapy or chemoendocrine therapy improve both the
      quantity and quality of life for patients with node-positive breast cancer
      compared with a single short course of perioperative combination chemotherapy.

PMID- 2003708
TI  - Long-term remission of chronic hepatitis B after alpha-interferon therapy.
AB  - OBJECTIVE: To evaluate whether remissions of chronic hepatitis B induced by alpha
      interferon therapy are of long duration. DESIGN: Cohort study. SETTING: Clinical
      Center of the National Institutes of Health, a tertiary referral center.
      PATIENTS: Sixty-four patients with chronic hepatitis B were treated with alpha
      interferon between 1984 and 1986. MAIN OUTCOME MEASURES: Patients were followed
      with frequent examinations and determinations of serum liver biochemical tests
      and hepatitis B virus (HBV) markers including hepatitis B surface antigen
      (HBsAg), hepatitis B e antigen (HBeAg), and HBV DNA using blot hybridization and
      polymerase chain reaction. RESULTS: Among 64 patients with chronic hepatitis B
      who were treated with alpha-interferon, 23 (36%) responded to treatment with loss
      of HBeAg and improvement in serum aminotransferases. All 23 have been followed
      for 3 to 7 years (mean, 4.3 years). During follow-up, 3 of 23 patients relapsed,
      with reappearance of HBeAg and abnormal serum aminotransferases, all within 1
      year of therapy. The remaining 20 patients continued to have no detectable HBeAg
      or HBV DNA (using blot hybridization) in serum and to be asymptomatic for liver
      disease, although 3 had minimal elevations in serum aminotransferases. Thirteen
      patients (65%) became negative for HBsAg between 0.2 and 6 years (mean, 3 years)
      after loss of HBeAg. Although no patient had HBV DNA that was detectable by blot
      hybridization, the 7 patients who remained HBsAg positive all had HBV DNA in
      serum detected by polymerase chain reaction, but only 2 of 13 HBsAg-negative
      patients had viral genome using this method. Testing sequential samples indicated
      that HBV DNA detected by polymerase chain reaction usually disappeared at or
      around the time that test results for HBsAg became negative. CONCLUSIONS:
      Remissions in chronic hepatitis B induced by alpha-interferon are of long
      duration and are followed, in most patients, by the loss of HBsAg and all
      evidence of residual virus replication.

PMID- 2003709
TI  - Emboli in infective endocarditis: the prognostic value of echocardiography.
AB  - OBJECTIVE: To determine whether vegetations visualized on two-dimensional
      echocardiography are an independent risk factor for the development of subsequent
      emboli in patients with infective endocarditis and to assess the timing of emboli
      relative to the initiation of antimicrobial therapy. DESIGN: Investigator
      blinded, retrospective incidence cohort study. SETTING: Tertiary referral center.
      PATIENTS: Patients with left-sided native valve infective endocarditis who had
      two-dimensional echocardiography within 72 hours of beginning antimicrobial
      therapy. MEASUREMENTS AND MAIN RESULTS: The crude incidence rate of first embolic
      events in patients receiving antimicrobial therapy was 6.2 per 1000 patient-days
      (95% CI, 4.2 to 9.2). The rates in patients with and without vegetations were 7.1
      and 4.9 per 1000 patient-days, respectively (incidence rate ratio, 1.4; 95% CI,
      0.6 to 3.3). The relation between vegetations and risk for emboli was
      microorganism-dependent: Stratified incidence rate ratios were 6.9 (95% CI, 1.1
      to 42.5; P less than 0.05) and 1.0 (95% CI, 0.2 to 3.9) for viridans
      streptococcal and Staphylococcus aureus endocarditis, respectively. The rate of
      first embolic events diminished over time (P less than 0.001), falling from 13
      per 1000 patient-days during the first week of therapy to less than 1.2 per 1000
      patient-days after completion of the second week of therapy. CONCLUSIONS:
      Overall, the presence of vegetations on echocardiography was not associated with
      a significantly higher risk for embolus in patients with left-sided native valve
      infective endocarditis. The relative risk for embolic events associated with
      echocardiographically visualized vegetations may be microorganism-dependent, with
      a significantly increased risk seen only in patients with viridans streptococcal
      infection. The rate of embolic events declines with time after initiation of
      antimicrobial treatment.

PMID- 2003710
TI  - The changing prognosis of classic hemophilia (factor VIII "deficiency").
AB  - OBJECTIVE: To estimate relative risk of mortality and median life expectancy for
      patients with classic hemophilia by a life-table analysis, taking into account
      deaths that may have occurred in infancy or childhood before the onset of
      symptoms. DESIGN: Retrospective chart review of clinical series. SETTING:
      Referral-based university medical center. PATIENTS: Seven hundred one patients
      with classic hemophilia (hemophilia A; factor VIII "deficiency") were studied for
      the years from 1900 to 1990; patients were identified in 289 families.
      MEASUREMENTS AND MAIN RESULTS: Relative risk for mortality and median life
      expectancy among hemophiliacs were compared with those among normal U.S. males.
      Overall, mortality (relative to that of contemporaneous U.S. males) was increased
      about sixfold among severely affected patients, more than twofold among
      moderately affected patients, and was equivalent to that of U.S. males among
      mildly affected patients. Median life expectancy at 1 year of age had reached
      almost 68 years in the decade 1971 to 1980, but declined to only 49 years in the
      decade 1981 to 1990. CONCLUSIONS: After improvement in survival from 1971-1980
      (corresponding to widespread treatment with lyophilized concentrates of
      antihemophilic factor [factor VIII]), relative mortality is now increasing,
      especially among severely affected patients, in large measure because of the
      acquired immunodeficiency syndrome (AIDS).

PMID- 2003711
TI  - Comparison of silent and symptomatic ischemia during exercise testing in men.
AB  - OBJECTIVE: To compare angina and ST-segment depression during exercise testing,
      as markers for coronary artery disease. DESIGN: Retrospective analysis of
      exercise test responses and cardiac catheterization results. SETTING: A U.S.
      Veterans Affairs medical center. PATIENTS: Four hundred and sixteen men who were
      referred for the evaluation of symptoms, postmyocardial infarction testing, or
      both. Two hundred patients had no clinical or electrocardiographic evidence of
      previous myocardial infarction, whereas 216 were survivors of a previous
      myocardial infarction. INTERVENTIONS: All patients did a standard exercise test
      and had diagnostic coronary angiography with ventriculography within an average
      of 32 days (range, 0 to 90 days) of their exercise test. RESULTS: Two hundred
      patients without a previous myocardial infarction were divided into four groups:
      the no ischemia group had 80 patients; the angina pectoris only group had 23
      patients; the silent ischemia group had 40 patients; and the ST-segment
      depression and angina pectoris group had 57 patients. In patients without a
      previous myocardial infarction, exercise-induced ST-segment depression was a
      better marker than exercise-induced angina for the presence of any coronary
      artery disease (P less than 0.005). Patients with symptomatic exercise-induced
      ischemia had a higher prevalence of severe coronary artery disease than did those
      with only silent ischemia (30% compared with 20%; 95% CI, - 7.3% to 27.0%; P =
      0.005). For the 216 survivors of a myocardial infarction, divided into the same
      four groups, ST-segment depression again was a better marker for the presence of
      severe coronary artery disease compared with angina alone (P = 0.08). The
      prevalence rates of severe coronary artery disease in the no ischemia plus
      myocardial infarction group, the angina pectoris only plus myocardial infarction
      group, the silent ischemia plus myocardial infarction group, and the ST-segment
      depression and angina pectoris plus myocardial infarction group were 10%, 9%,
      23%, and 32%, respectively (P less than 0.01). CONCLUSIONS: Exercise-induced ST
      segment depression is a better marker for coronary artery disease than is
      exercise-induced angina. Symptomatic ischemia during the exercise test is a
      better marker for severe coronary artery disease than is silent ischemia.

PMID- 2003712
TI  - Psychological and behavioral implications of abnormal mammograms.
AB  - OBJECTIVE: To evaluate women's psychological responses to abnormal mammograms and
      the effect on mammography adherence. To identify psychological responses and
      other factors that predict mammography adherence in women with normal or abnormal
      mammograms. DESIGN: Survey study with prospective analysis of factors associated
      with mammography adherence. SETTING: Health Maintenance Organization of
      Pennsylvania and New Jersey (HMO PA/NJ). PATIENTS: Study patients, members of HMO
      PA/NJ who were 50 years of age or older, and who had had mammography done 3
      months earlier, included women with normal mammograms (n = 121), women with low
      suspicion mammograms (n = 119), and women with high-suspicion mammograms (n =
      68), but not women with breast cancer. MEASUREMENTS: Psychological responses 3
      months after mammography and adherence to subsequent annual mammography were
      assessed. MAIN RESULTS: Women with high-suspicion mammograms had substantial
      mammography-related anxiety (47%) and worries about breast cancer (41%). Such
      worries affected the moods (26%) and daily functioning (17%) of these women,
      despite diagnostic evaluation excluding malignancy. For each variable, a
      consistent trend (P greater than 0.05) was seen with degree of mammogram
      abnormality. Sixty-eight percent of women with normal results, 78% of women with
      low-suspicion results, and 74% of women with high-suspicion results obtained
      their subsequent annual mammograms (P greater than 0.05). The number of previous
      mammograms (odds ratio, 3.2; 95% CI, 1.6 to 6.2) and the effect of the previous
      results on concerns about breast cancer (odds ratio, 0.5; CI, 0.2 to 1.0) were
      independent predictors of adherence in logistic regression analyses (P less than
      0.05). CONCLUSIONS: A substantial proportion of women with suspicious mammograms
      have psychological difficulties, even after learning that they do not have
      cancer. Such sequelae do not appear to interfere with subsequent adherence.

PMID- 2003713
TI  - Long-term follow-up of voluntary ingestion of Helicobacter pylori.

PMID- 2003714
TI  - Cardiopulmonary toxicity after liposomal amphotericin B infusion.

PMID- 2003715
TI  - Tolerance to organic nitrates: evidence, mechanisms, clinical relevance, and
      strategies for prevention.
AB  - OBJECTIVE: To review the available information about nitrate tolerance, its
      potential mechanisms, clinical implications, and strategies for prevention. DATA
      IDENTIFICATION: A survey of the National Library of Medicine MEDLINE database and
      bibliographies of the reviewed articles. STUDY SELECTION AND DATA EXTRACTION:
      Studies were selected from the English language literature with an emphasis on
      recent studies and, when available, randomized placebo-controlled studies. Old
      studies were selected on the basis of their historical value and originality. A
      total of 134 retrieved articles were considered relevant and were reviewed in
      depth. RESULTS: The available information about the experimental as well as the
      clinical evidence for tolerance to organic nitrates has been summarized. In
      addition, information related to potential mechanisms, clinical implications, and
      possible methods for prevention have been reviewed. CONCLUSIONS: Evidence
      indicates that prolonged in-vitro exposure to organic nitrates, continuous
      intravenous or topical administration of nitrates, and frequent in-vivo oral
      dosing result in the rapid development of tolerance to the peripheral as well as
      to the coronary vasodilatory effects of the drugs. This phenomenon leads to the
      rapid attenuation of the hemodynamic and anti-ischemic effects of nitrates in
      patients with ischemic heart disease or congestive heart failure, or both.
      Tolerance development seems to be dose- and time-dependent, and its main
      mechanism seems to be a depletion of sulfhydryl groups at the vascular cell.
      Although the repletion of sulfhydryl groups with the use of sulfhydryl-containing
      drugs may help to prevent tolerance, the efficacy and safety of this approach
      requires further evaluation. Intermittent therapy allowing a sufficiently long,
      daily nitrate-washout interval seems to be the most effective and the most safe
      strategy currently available for the prevention of nitrate tolerance.

PMID- 2003716
TI  - Heal thyself.

PMID- 2003717
TI  - The quality of life, research, and care.

PMID- 2003718
TI  - Gene therapy in humans: a new era begins.

PMID- 2003719
TI  - Early release of research results.

PMID- 2003720
TI  - Streptokinase for inferior myocardial infarction.

PMID- 2003721
TI  - Predicting bacteremia.

PMID- 2003722
TI  - Outcomes of carotid endarterectomy.

PMID- 2003723
TI  - Corticosteroids for chronic obstructive pulmonary disease.

PMID- 2003724
TI  - MRSA in perspective.

PMID- 2003725
TI  - Dexamethasone for alcohol withdrawal.

PMID- 2003726
TI  - Prevention: where do we draw the line?

PMID- 2003727
TI  - AORN's vision of the future has no room for archaic notions.

PMID- 2003728
TI  - AORN should accept ANA affiliate status.

PMID- 2003729
TI  - New federal agencies charged with examining effectiveness of health care
      interventions.

PMID- 2003730
TI  - Shared governance for nursing. Part I: Creating the new organization.
AB  - In Part I, the concept of shared governance is presented. I have discussed what
      it means to move toward a shared governance model and the way of thinking and
      reorganizing that supports it. Basic principles that drive the concept are
      discussed, and the underpinnings necessary to make it work are identified.
      Clearly, the move toward shared governance is not simply an organizational
      transition. It is a method for transforming the way we work and make decisions.
      Part II will examine how roles are changed. The management function, the impact
      of shared governance on its function, and changes in the manager's behavior will
      be identified. In Part II, the importance of peer processes and supports for
      ensuring that changes are carried out by staff leadership are discussed. A new
      way of composing and exercising the executive function in a professional
      organization also will be discussed.

PMID- 2003731
TI  - The nurse as inventor. Obtain a patent and benefit from your ideas.

PMID- 2003732
TI  - Proposed recommended practices. Aseptic technique. AORN Recommended Practices
      Coordinating Committee.

PMID- 2003733
TI  - Documentation, counts cause concern.

PMID- 2003734
TI  - Operating room construction requirements; disinfecting floors; floating nurses.

PMID- 2003735
TI  - Disk operating systems: what they are and how they operate.

PMID- 2003736
TI  - [Paraneoplastic syndrome hematologic abnormalities].
AB  - The paraneoplastic syndrome (PNS) is an association of symptoms and signs not
      directly related to the site or local manifestations of a malignant tumor or its
      metastases. Hematologic abnormalities as PNS include erythrocytosis, anemia,
      neutrophilia, neutropenia, eosinophilia, thrombocytosis, thrombocytopenia, venous
      thromboembolism and disseminated intravascular coagulation (DIC). These
      abnormalities are, by and large, due to the production of biologically active
      growth factors, hormones or as yet unidentified "humors" by the tumor. As our
      understanding of growth factors controlling hematopoiesis has increased in recent
      years, the biologic basis of hematologic PNS are better understood. For instance,
      tumor-associated neutrophilia is now known to be caused by the production of G
      CSF by the tumor. The mechanism by which tumor causes thromboembolism have also
      been extensively investigated. Cancer cells induce platelet aggregation both in
      vitro and in vivo. Platelet aggregating material has been isolated and partially
      characterized from tumor cells. The involvement of platelet glycoprotein II
      b/IIIa in the tumor-platelet interaction has also been shown. Malignant cells
      contain a unique procoagulant, cancer procoagulant A, that directly activates
      factor X. Together with tissue factor, this procoagulant appears to have been
      contribute to a high incidence of thromboembolism in cancer patients. Better
      understanding of hematologic PNS is important for clinical care of the patients
      with cancer.

PMID- 2003737
TI  - [Malignancy-associated hypercalcemia].
AB  - Hypercalcemia is the most frequent paraneoplastic syndrome observed in cancer
      patients. This morbidity can be divided into two categories: one is hypercalcemia
      induced by severe bone metastases; the other the elaboration of hypercalcemic
      factors by solid tumors, termed humoral hypercalcemia of malignancy (HHM). With
      regard to humoral factors responsible for HHM, a protein with parathyroid hormone
      (PTH)-like activity, designated PTH-related protein (PTHrP), was isolated from a
      cancer cell line established from a hypercalcemic patient's lung cancer tissue,
      and the structure of PTHrP mRNA was identified. Since the biological activity of
      PTHrP explained most of the clinical and laboratory findings of HHM patients and
      recent clinical studies indicated the very close relationship between the
      development of HHM and the production of PTHrP by tumor, PTHrP is now regarded to
      be the primary candidate for the actual factor responsible for HHM.

PMID- 2003738
TI  - [Skin manifestation of internal malignancy].
AB  - Relationship between malignant tumor of the internal organ and the skin can be
      classified as skin metastasis of the malignant tumor, non-specific skin
      manifestation of the malignant tumor and hereditary syndrome which tends to have
      malignant tumor. I, however, discuss here mainly about the non-specific
      manifestation of the malignant tumor by showing representative cases of the
      dermadrome. Such cases are acanthosis nigricans, Leser-Trelat's sign,
      dermatomyositis, atypical erythema, acquired ichthyosis, Sweet's disease, Weber
      Christian's syndrome, phlebitis migrans and Bazex syndrome.

PMID- 2003739
TI  - [Distribution and acute toxicity of a new morpholinoanthracycline, MX2, in normal
      rat brain after intra-arterial injection].
AB  - Intra-arterial infusion chemotherapy has been applied for the treatment of
      malignant brain tumors to increase the distribution of the drug into the tumor.
      MX2, a new morpholinoanthracycline, is a lipophilic compound, and has a strong
      antineoplastic effect against human and rat glioma cells. In this report, the
      acute toxicity and distribution of MX2 after intracarotid injection were studied
      using female Wistar rats weighing 150 g. To test the acute toxicity, various
      doses ranging 1.5 to 6 mg/kg was administered. All rats died within 4 days when
      received more than 3 mg/kg of intra-arterial or intravenous MX2. No rats died if
      the dose was reduced to less than 2 mg/kg. For the purpose to examine
      distribution in the brain, rats which received 2 mg/kg of intra-carotid MX2 were
      killed 5 to 120 min. after injection. The level of MX2 in the ipsilateral brain
      tissue reached to the maximum 5 min. after injection, and then rapidly decreased.
      The maximum concentration of MX2 in the ipsilateral brain was 25-fold higher than
      that in the contralateral brain, and 20-fold higher than that after intravenous
      injection of the same dose. The AUC (area under the curve) in the ipsilateral
      brain after intra-carotid injection was 8.0-fold higher than that in the
      contralateral brain, and 7.3-fold higher than that after intravenous injection of
      the same dose. These results indicate that intra-carotid administration can
      increase the distribution of MX2 in the normal brain.

PMID- 2003740
TI  - [Mechanism for synergistic antitumor effect in the combination of 5-fluorouracil
      with cisplatin in vivo tumor models: from the view of biochemical modulation of 5
      fluorouracil].
AB  - The mechanism for 5-fluorouracil (5-FU) and cisplatin (CDDP) synergism was
      investigated in experimental tumor models in rodents in vivo. The reduced folates
      such as 5, 10-methylenetetrahydrofolate (CH2FH4) and tetrahydrofolate (FH4) which
      play a significant role in the metabolism of 5-FU were increased about 2 to 3
      fold 5 in P388 and Yoshida sarcoma cells of rodents at 24 hours following
      intraperitoneal administration of CDDP (5 mg/kg), and tritiated 2'-deoxyuridine
      incorporation into DNA fraction of the CDDP-treated cells was more strongly
      inhibited than that of non-treated cells after incubation with 5-FU, which
      indicated the increased formation of a tight ternary complex between thymidylate
      synthase, FdUMP derived from 5-FU and elevated CH2FH4. The combination of single
      intraperitoneal CDDP and 6 day-continuous infusion of 5-FU and/or 7 consecutive
      oral administration 5-FU derivative, BOF-A2, enhanced synergistically the
      antitumor activity against solid Yoshida sarcomas in rats as compared to each
      drug alone. These data suggest that CDDP play an important role as not only an
      effector but also a modulator in biochemical modulation of 5-FU in cellular
      methionine metabolism and by resultant elevation of intracellular reduced
      folates.

PMID- 2003741
TI  - [Clinical study of eel calcitonin for relief of pain from metastatic bone
      lesions].
AB  - Thirty patients with bone metastasis were treated with eel calcitonin (CT) to
      relieve severe pain from metastatic bone lesions. Patients were two males and
      twenty-eight females with a mean age of 52.8. CT was administered intramuscularly
      in twenty-seven patients and intravenously in three. CT was effective on 55.6% of
      patients to reduce severe bone pain but did not decrease the amount of analgesics
      in most patients. Serum Ca and P were not changed markedly. As side-effects, two
      patients complained of nausea and vomiting after administration of CT but they
      weren't severe. These results indicate that CT is quite useful drug for relief of
      severe bone pain from metastatic lesions in patients with breast or digestive
      tract carcinomas.

PMID- 2003742
TI  - [Feasibility study of quality of life (QOL) instrument in patients with advanced
      lung cancer].
AB  - We have studied the feasibility of the QOL measurement for the group of patients
      with advanced lung cancer using the QOL questionnaires modified from FLIC
      (Functional Living Index Cancer). The 16-items instrument showed that the
      Cronbach's alpha of all categories were over 0.6. as the quality of reliability.
      Using the principal component method of multivariate analysis, four major factors
      were identified as a part of the construct validity. We concluded that the QOL of
      patients with advanced lung cancer under the clinical research setting can be
      evaluated using this questionnaires even in Japan which has different cultural
      background from the Western Countries.

PMID- 2003743
TI  - [A case of effective preoperative chemotherapy in alveolar soft part sarcoma].
AB  - Alveolar soft part sarcoma is primarily treated by surgery, and reports of
      effective chemotherapy have been infrequent. We experienced a patient with
      alveolar soft part sarcoma in the left thigh, in whom preoperative chemotherapy
      with cisplatinum (CDDP) and adriamycin (ADM) was effective. This patient was a 13
      year-old male who had an elastic hard mass with the size of his fist in the
      medial thigh. Plain X-ray revealed bone destruction with periosteal reactions in
      the distal diaphysis of the femur. Biopsy specimen showed alveolar growth of
      relatively large cells with eosinophilic or clear cytoplasm. PAS staining was
      positive in microgranular patterns in part of the cells, but no crystalline
      structure were observed. A diagnosis of alveolar soft part sarcoma was made, and
      chemotherapy was started. After administration of 150 mg of CDDP intraarterially
      twice and 50 mg of ADM intravenously 5 times, effectiveness of chemotherapy was
      estimated by physical and radiological findings. In the resected specimen, the
      margins of the soft part tumor showed shell-like ossification, suggesting the
      subperiosteal or intraosteal origin. Histology of the removed specimen showed
      that the tumor was mostly replaced by fibrous tissues, indicating the
      effectiveness of the preoperative chemotherapy. This disease has a relatively
      long course, however, the present case is considered to be another exceptional
      case that responded to preoperative chemotherapy.

PMID- 2003744
TI  - [Therapeutic efficacy of etoposide injected via carotid artery with angiotensin
      II-induced hypertension in experimental rat gliomas].

PMID- 2003745
TI  - [Tumor marker--personal experience. Mass survey and outpatients screening of
      pancreatic cancer].
AB  - To investigate the possibility that to detect carcinoma of the pancreas at an
      early stage by mass survey or outpatients screening, we performed the
      multicentral study for pancreatic cancer in Japan for two years from 1984 to
      1985, using serum CA 19-9 and elastase-1 determinations or ultrasonography. Only
      4 cases of pancreatic cancer were found out by mass survey, and according to
      outpatients screening with gastrointestinal complaints or jaundice, 85 patients
      were found to have pancreatic cancer. These results suggest that mass screening
      of persons without symptom is not worthy of the early detection of pancreatic
      cancer, however, outpatients screening gis useful for detecting curative cancers
      of the pancreas.

PMID- 2003746
TI  - ANNA long-range planning: historical overview.
AB  - Long-range planning is essential to organizational survival but developing a plan
      is only the beginning. Developing yearly action plans to meet objectives and
      revising plans as necessary are ongoing responsibilities of the governing board,
      national committees, and staff. ANNA has been extremely successful with planning
      efforts throughout its history, primarily because it was responsive to its
      members. The association was not always on track, but it was never far away.
      Approaches to planning have become more sophisticated over the last 10 years, but
      earlier planning efforts were just as effective. We can gain reaffirmation of
      important organizational concepts from historical review. These are: (a) the life
      blood of the association is its members; (b) ideas for needed services are only
      valid if they represent the stated interests of the practitioner; (c)
      associations that offer unwanted services are doomed to fail; and (d) the
      continuing input from all members is essential to continued growth. As you read
      through the following articles on planning, keep in mind those goals established
      by our founding members, appreciate how insightful, progressive, and accurate
      they were even if their goals were not always understood, appreciated, or
      universally accepted at the time. Current long range plans and today's concepts
      for the future may be received in a similar fashion with great interest and
      enthusiasm by some and with increduality or total confusion by others. The goals
      deserve discussion and feedback--it is the member's right and responsibility to
      do so and it is critical to the future of ANNA. Nephrology nurses are as unique
      today as they were in the early 1960s. Through our professional home, ANNA, we
      have the power to achieve more for our specialty nursing practice than ever
      before, and, to share our work with sister organizations throughout the world.
      All it takes is planning.

PMID- 2003747
TI  - A time for change.

PMID- 2003749
TI  - Implementation of ANNA's new long-range strategic plan.

PMID- 2003748
TI  - Format of ANNA's long-range strategic plan.
AB  - In summary, ANNA's Long Range Strategic Plan is a working tool. This is not a
      document to gather dust. The format lends itself to use by a Board of Directors
      with information and direction flowing to the committee level and then the
      evaluation process sending information flowing back to the Board of Directors.
      This is the key to any successful strategic plan.

PMID- 2003750
TI  - Creating your contribution to nursing's future.

PMID- 2003751
TI  - Reaction of patients on chronic dialysis to discussions about cardiopulmonary
      resuscitation.
AB  - A total of 146 patients, 91 on chronic hemodialysis and 55 on chronic peritoneal
      dialysis, were asked to declare their choice of cardiopulmonary resuscitation
      (CPR) in cases of cardiopulmonary arrest. Fifty-four patients (37%) declined CPR.
      The severity of medical disability and the presence of diabetes were independent
      predictors of refusal of CPR. The pattern of patient reaction to CPR gave
      valuable information about patients' comprehension of this issue and about
      patients' ability to cope emotionally with CPR. On the basis of the reaction
      pattern, approximately 95% of the patients interviewed understood CPR and reacted
      to it appropriately. Questioning dialysis patients about their CPR preference is
      feasible and fruitful.

PMID- 2003753
TI  - Oral care for the renal transplant patient.
AB  - Renal transplant patients require immunosuppressive therapy, including a
      combination of prednisone, methylprednisone, azathioprine, antilymphocyte
      globulins, cyclosporine, and/or OKT 3. Consequently, they are vulnerable to
      opportunistic infections, especially in the oral cavity. The infections often
      seen are candida albicans and herpes simplex virus. Routine oral assessments and
      oral care need to be performed to provide maximum patient comfort and to prevent
      or minimize painful complications.

PMID- 2003752
TI  - Streamlining orientation for hemodialysis nursing: a competency-based approach.
AB  - Orientation of a nephrology nurse in a hemodialysis setting is a complex process;
      often stressful for the learner and time consuming for the educator. The extent
      of orientation depends upon individual learning needs and previous clinical
      experience. The competency-based approach to orientation in hemodialysis is
      comprehensive, efficient, and cost-effective. Modular in design, it is adaptable
      to varying levels of orientation needs. Based on andragogical theory, it is goal
      oriented and learner-directed. A manual has been developed to facilitate a
      competency-based orientation in hemodialysis. The manual is an outcome-driven
      tool designed to integrate the nursing process with dialysis technology. The
      focus is maximization of nephrology nursing care resulting in enhanced patient
      outcomes.

PMID- 2003755
TI  - HIV infection and the kidney.

PMID- 2003754
TI  - Applying Orem's theory to the long-term care of adolescent transplant recipients.
AB  - The nursing theory of Dorothea Orem is applied to the care of the adolescent
      transplant recipient in the long-term setting of outpatient services. The theory
      of self-care is used as a framework to organize and direct nursing services to
      this select population. The following article discusses the framework that
      significantly contributes to maximizing the potential and quality of life for
      each recipient and assures the quality and utility of professional nursing
      services.